anchor_id
stringlengths 8
8
| anchor_title
stringlengths 5
839
| anchor_abstract
stringlengths 2
61.6k
| positive_pool
listlengths 1
1
| negative_pool
listlengths 1
1
|
|---|---|---|---|---|
28759998
|
Pharmacist Participation in Acute Ischemic Stroke Decreases Door-to-Needle Time to Recombinant Tissue Plasminogen Activator.
|
Pharmacists are an important member of the stroke team and aid in obtaining medication and medical history, providing education, managing blood pressure, reviewing exclusion criteria for recombinant tissue plasminogen activator (rtPA), and facilitating reconstitution and administration of rtPA.</AbstractText To determine if pharmacist presence at bedside during acute ischemic stroke resulted in a reduction in door-to-needle (DTN) times.</AbstractText This was a retrospective cohort study between January 1, 2011 and December 31, 2015 of patients who received rtPA for acute ischemic stroke in either the emergency department or hospital.</AbstractText Of the 125 included patients, 45 patients (36%) had a pharmacist present (PharmD group) and 80 patients (64%) did not (no PharmD group). Median DTN time was significantly shorter in the PharmD group: 48 minutes versus 73 minutes in the no PharmD group ( P < 0.01). The goal of DTN ≤60 minutes was met in 71% of patients in the PharmD group compared to 29% ( P < 0.01). Pharmacist at the bedside was the only factor found to be independently associated with reduction DTN time (βcoefficient -23.5 minutes, 95% confidence interval [95% CI] -38.6 to -8.50 minutes).</AbstractText A pharmacist at the bedside of emergency department or in-patient stroke codes reduced DTN time by a median of 23.5 minutes after adjusting for confounding factors and increased the percentage of patients meeting DTN goal time of ≤60 minutes by 49%. These findings support the inclusion of a stroke-competent pharmacist in the bedside response team for acute ischemic stroke patients.</AbstractText
|
[
[
"27110714",
"Correction for Inhibition Leads to an Allosteric Co-Agonist Model for Pentobarbital Modulation and Activation of α1β3γ2L GABAA Receptors.",
"Pentobarbital, like propofol and etomidate, produces important general anesthetic effects through GABAA receptors. Photolabeling also indicates that pentobarbital binds to some of the same sites where propofol and etomidate act. Quantitative allosteric co-agonist models for propofol and etomidate account for modulatory and agonist effects in GABAA receptors and have proven valuable in establishing drug site characteristics and for functional analysis of mutants. We therefore sought to establish an allosteric co-agonist model for pentobarbital activation and modulation of α1β3γ2L receptors, using a novel approach to first correct pentobarbital activation data for inhibitory effects in the same concentration range.</AbstractText Using oocyte-expressed α1β3γ2L GABAA receptors and two-microelectrode voltage-clamp, we quantified modulation of GABA responses by a low pentobarbital concentration and direct effects of high pentobarbital concentrations, the latter displaying mixed agonist and inhibitory effects. We then isolated and quantified pentobarbital inhibition in activated receptors using a novel single-sweep \"notch\" approach, and used these results to correct steady-state direct activation for inhibition.</AbstractText Combining results for GABA modulation and corrected direct activation, we estimated receptor open probability and optimized parameters for a Monod-Wyman-Changeux allosteric co-agonist model. Inhibition by pentobarbital was consistent with two sites with IC50s near 1 mM, while co-agonist model parameters suggest two allosteric pentobarbital agonist sites characterized by KPB ≈ 5 mM and high efficacy. The results also indicate that pentobarbital may be a more efficacious agonist than GABA.</AbstractText Our novel approach to quantifying both inhibitory and co-agonist effects of pentobarbital provides a basis for future structure-function analyses of GABAA receptor mutations in putative pentobarbital binding sites.</AbstractText"
]
] |
[
[
"28285191",
"Polychlorinated biphenyls-153 induces metabolic dysfunction through activation of ROS/NF-κB signaling via downregulation of HNF1b.",
"Polychlorinated biphenyls (PCB) is a major type of persistent organic pollutants (POPs) that act as endocrine-disrupting chemicals. In the current study, we examined the mechanism underlying the effect of PCB-153 on glucose and lipid metabolism in vivo and in vitro. We found that PCB-153 induced per se and worsened high fat diet (HFD)-resulted increase of blood glucose level and glucose and insulin intolerance. In addition, PCB-153 induced per se and worsened HFD-resulted increase of triglyceride content and adipose mass. Moreover, PCB-153 concentration-dependently inhibited insulin-dependent glucose uptake and lipid accumulation in cultured hepatocytes and adipocytes. PCB-153 induced the expression and nuclear translocation of p65 NF-κB and the expression of its downstream inflammatory markers, and worsened HFD-resulted increase of those inflammatory markers. Inhibition of NF-κB significantly suppressed PCB-153-induced inflammation, lipid accumulation and decrease of glucose uptake. PCB-153 induced oxidative stress and decreased hepatocyte nuclear factor 1b (HNF1b) and glutathione peroxidase 1 (GPx1) expression in vivo and in vitro. Overexpression of HNF1b increased GPx1 expression, decreased ROS level, decreased Srebp1, ACC and FAS expression, and inhibited PCB-153-resulted oxidative stress, NF-κB-mediated inflammation, and final glucose/lipid metabolic disorder. Our results suggest that dysregulation of HNF1b/ROS/NF-κB plays an important role in PCB-153-induced glucose/lipid metabolic disorder.</AbstractText"
]
] |
35993408
|
A Novel Dynamin 2 Mutation Causing Dominant Intermediate Charcot-Marie-Tooth Neuropathy: Case Report.
|
Dynamin 2 mutations are associated with Charcot-Marie-Tooth neuropathy. We report two siblings with a novel missense heterozygous point mutation (c.1609 G>A) in the highly conserved pleckstrin homology domain in exon 15 of Dynamin 2 presenting with progressive length-dependent sensorimotor polyneuropathy with mixed demyelinating and axonal features on electrodiagnostic studies. The previously unrecognized missense point mutation, which was inherited from their symptomatic but previously undiagnosed mother, was determined to be likely pathogenic based on a non-conservative amino acid substitution (p.Gly537Ser) that is predicted to damage secondary protein structure or function. This report emphasizes the importance of recognizing inherited neuropathies in clinical practice and evaluating suspected pathogenic gene variants initially classified to be of undetermined clinical significance in family cohorts. These cases add to the spectrum of pathogenic Dynamin 2 mutations associated with dominant-intermediate Charcot-Marie-Tooth neuropathy.</AbstractText
|
[
[
"31069783",
"A novel WARS mutation (p.Asp314Gly) identified in a Chinese distal hereditary motor neuropathy family.",
"Distal hereditary motor neuropathy (dHMN) is a clinically and genetically heterogeneous group of inherited neuropathies characterized by distal limb muscle wasting and weakness with no or minimal sensory abnormalities. To investigate the clinical and genetic features of dHMN caused by WARS mutations in mainland China, we performed Sanger sequencing of the coding and untranslated region (UTR) regions of WARS in 160 unresolved dHMN and Charcot-Marie-Tooth (CMT) index patients. We detected a novel heterozygous variant c.941A>G (p.Asp314Gly) of WARS in an index patient from an autosomal dominant dHMN family including five affected members over three generations. The variant completely co-segregates with the dHMN phenotype in the family, and it was classified as likely pathogenic according to the American College of Medical Genetics and Genomics standards and guidelines. The clinical features included juvenile to adult onset (15-23 years), distal wasting and weakness, minimal sensory disturbance and length-dependent motor axonal degeneration with CMT examination score ranging from 6 to 10. Our report further confirms the role of WARS in dHMN and indicates that the variant c.941A>G (p.Asp314Gly) of WARS is related to a mild to moderate affected and later onset phenotype of dHMN.</AbstractText"
]
] |
[
[
"34686764",
"Altered functional brain dynamics in chromosome 22q11.2 deletion syndrome during facial affect processing.",
"Chromosome 22q11.2 deletion syndrome (22q11.2DS) is a multisystem disorder associated with multiple congenital anomalies, variable medical features, and neurodevelopmental differences resulting in diverse psychiatric phenotypes, including marked deficits in facial memory and social cognition. Neuroimaging in individuals with 22q11.2DS has revealed differences relative to matched controls in BOLD fMRI activation during facial affect processing tasks. However, time-varying interactions between brain areas during facial affect processing have not yet been studied with BOLD fMRI in 22q11.2DS. We applied constrained principal component analysis to identify temporally overlapping brain activation patterns from BOLD fMRI data acquired during an emotion identification task from 58 individuals with 22q11.2DS and 58 age-, race-, and sex-matched healthy controls. Delayed frontal-motor feedback signals were diminished in individuals with 22q11.2DS, as were delayed emotional memory signals engaging amygdala, hippocampus, and entorhinal cortex. Early task-related engagement of motor and visual cortices and salience-related insular activation were relatively preserved in 22q11.2DS. Insular activation was associated with task performance within the 22q11.2DS sample. Differences in cortical surface area, but not cortical thickness, showed spatial alignment with an activation pattern associated with face processing. These findings suggest that relative to matched controls, primary visual processing and insular function are relatively intact in individuals with 22q11.22DS, while motor feedback, face processing, and emotional memory processes are more affected. Such insights may help inform potential interventional targets and enhance the specificity of neuroimaging indices of cognitive dysfunction in 22q11.2DS.</AbstractText"
]
] |
40269690
|
Prediction model and scoring system for the risk of atrial fibrillation recurrence in patients with atrial fibrillation and obstructive sleep apnoea syndrome: a retrospective case-control study.
|
The high prevalence of atrial fibrillation (AF) and obstructive sleep apnea syndrome (OSAS) imposes a substantial disease burden on public healthcare, making it a significant health concern in the current era. However, there is currently a lack of risk assessment tools for AF recurrence in patients with AF and OSAS. Therefore, this study aims to explore the factors influencing AF recurrence in patients with AF and OSAS, and to establish a predictive model and scoring system for AF recurrence rates.</AbstractText The study included a total of 423 patients with AF and OSAS, who were randomly divided into train set (n = 296) and test set (n = 127) in a ratio of 7:3. Afterwards, the train set was split into a recurrence group and a non-recurrence group for further analysis of indicators while in hospital.</AbstractText Following Lasso regression screening, 8 variables were selected from a pool of 62 variables from patients with AF and OSAS. Additionally, the study incorporated the CHA<sub The predictive models and scoring systems developed in this study demonstrate good predictive ability in assessing the recurrence of AF in patients with OSAS, offering invaluable clinical guidance and references.</AbstractText Not applicable.</AbstractText
|
[
[
"20725915",
"Blood oxygenation level-dependent activation in basal ganglia nuclei relates to specific symptoms in de novo Parkinson's disease.",
"To aid the development of symptomatic and disease modifying therapies in Parkinson's disease (PD), there is a strong need to identify noninvasive measures of basal ganglia (BG) function that are sensitive to disease severity. This study examines the relation between blood oxygenation level-dependent (BOLD) activation in every nucleus of the BG and symptom-specific disease severity in early stage de novo PD. BOLD activation measured at 3 T was compared between 20 early stage de novo PD patients and 20 controls during an established precision grip force task. In addition to the BG nuclei, activation in specific thalamic and cortical regions was examined. There were three novel findings. First, there were significant negative correlations between total motor Unified PD Rating Scale and BOLD activation in bilateral caudate, bilateral putamen, contralateral external segment of the globus pallidus, bilateral subthalamic nucleus, contralateral substantia nigra, and thalamus. Second, bradykinesia was the symptom that most consistently predicted BOLD activation in the BG and thalamus. Also, BOLD activation in the contralateral internal globus pallidus was related to tremor. Third, the reduced cortical activity in primary motor cortex and supplementary motor area in de novo PD did not relate to motor symptoms. These findings demonstrate that BOLD activity in nuclei of the BG relates most consistently to bradykinesia and functional magnetic resonance imaging has strong potential to serve as a noninvasive marker for the state of BG function in de novo PD.</AbstractText"
]
] |
[
[
"40515391",
"Gene Swin transformer: new deep learning method for colorectal cancer prognosis using transcriptomic data.",
"Transcriptome sequencing has become essential in clinical tumor research, providing in-depth insights into the biology and functionality of tumor cells. However, the vast amount of data generated and the complex relationships between gene expressions make it challenging to effectively identify clinically relevant information. In this study, we developed a method called Gene Swin Transformer to address these challenges. This approach converts transcriptomic data into Synthetic Image Elements (SIEs). We utilized data from 12 datasets, including GSE17536-GSE103479 datasets (n = 1771) and The Cancer Genome Atlas (n = 459), to generate SIEs. These elements were then classified based on survival time using deep learning algorithms to predict colorectal cancer prognosis and build a reliable prognostic model. We trained and evaluated four deep learning models-BeiT, ResNet, Swin Transformer, and ViT Transformer-and compared their performance. The enhanced Swin-T model outperformed the other models, achieving weighted precision, recall, and F1 scores of 0.708, 0.692, and 0.705, respectively, along with area under the curve values of 80.2%, 72.7%, and 76.9% across three datasets. This model demonstrated the strongest prognostic prediction capabilities among those evaluated. Additionally, the PEX10 gene was identified as a key prognostic marker through both visual attention matrix analysis and bioinformatics methods. Our study demonstrates that the Gene Swin model effectively transforms Ribonucleic Acid (RNA) sequencing data into SIEs, enabling prognosis prediction through attention-based algorithms. This approach supports the development of a data-driven, unified, and automated model, offering a robust tool for classification and prediction tasks using RNA sequencing data. This advancement presents a novel clinical strategy for cancer treatment and prognosis forecasting.</AbstractText"
]
] |
22890939
|
SNR-optimized phase-sensitive dual-acquisition turbo spin echo imaging: a fast alternative to FLAIR.
|
Phase-sensitive dual-acquisition single-slab three-dimensional turbo spin echo imaging was recently introduced, producing high-resolution isotropic cerebrospinal fluid attenuated brain images without long inversion recovery preparation. Despite the advantages, the weighted-averaging-based technique suffers from noise amplification resulting from different levels of cerebrospinal fluid signal modulations over the two acquisitions. The purpose of this work is to develop a signal-to-noise ratio-optimized version of the phase-sensitive dual-acquisition single-slab three-dimensional turbo spin echo. Variable refocusing flip angles in the first acquisition are calculated using a three-step prescribed signal evolution while those in the second acquisition are calculated using a two-step pseudo-steady state signal transition with a high flip-angle pseudo-steady state at a later portion of the echo train, balancing the levels of cerebrospinal fluid signals in both the acquisitions. Low spatial frequency signals are sampled during the high flip-angle pseudo-steady state to further suppress noise. Numerical simulations of the Bloch equations were performed to evaluate signal evolutions of brain tissues along the echo train and optimize imaging parameters. In vivo studies demonstrate that compared with conventional phase-sensitive dual-acquisition single-slab three-dimensional turbo spin echo, the proposed optimization yields 74% increase in apparent signal-to-noise ratio for gray matter and 32% decrease in imaging time. The proposed method can be a potential alternative to conventional fluid-attenuated imaging.</AbstractText
|
[
[
"16155898",
"New insights into the mechanisms of signal formation in RF-spoiled gradient echo sequences.",
"RF spoiling is a well established method to produce T(1)-weighted images with short repetition-time gradient-echo sequences, by eliminating coherent transverse magnetization with appropriate RF phase modulation. This paper presents 2 novel approaches to describe signal formation in such sequences. Both methods rely on the formulation of RF spoiling as a linear increase of the precession angle between RF pulses, which is an alternative to the commonly used quadratic pulse phase scheme. The first technique demonstrates that a steady state signal can be obtained by integrating over all precession angles within the voxel, in spite of the lack of a genuine steady-state for separate isochromats. This clear mathematical framework allows a straightforward incorporation of off-resonance effects and detector phase settings. Moreover, it naturally introduces the need for a large net gradient area per repetition interval. In the second step, a modified partition method including RF spoiling is developed to obtain explicit expressions for all signal components. This provides a physical interpretation of the deviations from ideal spoiling behavior in FLASH and echo-shifted sequences. The results of the partition method in the small flip angle regime are compared with numerical simulations based on a Fourier decomposition of magnetization states. Measurements performed with in vitro solutions were in good agreement with numerical simulations at short relaxation times (T(1)/TR = 32 and T(2)/TR = 4); larger deviations occurred at long relaxation times (T(1)/TR = 114 and T(2)/TR = 82).</AbstractText"
]
] |
[
[
"23992544",
"Evaluation of the insulin releasing and antihyperglycaemic activities of GPR55 lipid agonists using clonal beta-cells, isolated pancreatic islets and mice.",
"G-protein coupled receptor (GPR)55 is a novel lipid sensing receptor activated by both cannabinoid endogenous ligands (endocannabinoids) and other non-cannabinoid lipid transmitters. This study assessed the effects of various GPR55 agonists on glucose homeostasis.</AbstractText Insulin secretion and changes in intracellular Ca(2) (+) and cAMP in response to glucose and a range of GPR55 agonists [endogenous ligands (OEA, PEA), chemically synthetic cannabidiol (CBD) analogues (Abn-CBD, 0-1602), an analogue of rimonabant (AM-251) and antagonist (CBD)] were investigated in clonal BRIN-BD11 cells and mouse pancreatic islets. Cytotoxicity was assessed by LDH release, cellular localization by double-staining immunohistochemistry and in vivo effects assessed in mice.</AbstractText The most potent and selective GPR55 agonist was the synthetic CBD analogue, Abn-CBD (pEC50 10.33), maximum stimulation of 67% at 10(-4)  mol·L(-1) (P < 0.001) in BRIN-BD11 cells. AM-251 (pEC50 7.0), OEA (pEC50 7.0), 0-1602 (pEC50 7.3) and PEA (pEC50 6.0) stimulated insulin secretion. Results were corroborated by islet studies, with no cytotoxic effects. Concentration-dependent insulin secretion by GPR55 agonists was glucose-sensitive and accompanied by elevations of [Ca(2) (+) ]i (P < 0.01-P < 0.001) and cAMP (P < 0.05-P < 0.01). GPR55 agonists exhibited insulinotropic and glucose lowering activity in vivo. GPR55 was expressed on BRIN-BD11 cells and confined to islet beta cells with no distribution on alpha cells.</AbstractText These results demonstrate GPR55 is distributed in pancreatic beta cells and is a strong activator of insulin secretion, with glucose-lowering effects in vivo. Development of agents agonizing the GPR55 receptor may have therapeutic potential in the treatment of type 2 diabetes.</AbstractText"
]
] |
40772448
|
Wishes, conflicts, and support needs of informal caregivers of patients in the palliative phase: A qualitative study.
|
This study explored wishes, conflicts, beneficial, and wished support of informal caregivers (ICGs) providing care to a palliative ill close other. We interviewed five current and 15 bereaved ICGs (25-75 years), and used thematic analyses. ICGs wished to continue life as normal as possible, spend time together and with their family, comfort their close other, and continue own activities. Caregivers experienced conflicts in balancing caregiving and own activities, quality time with each other and social contacts, the level of professional or informal support preferred, and in their shifting role from partner/child to nurse. ICGs experienced practical support, being heard, and good professional support as helpful. An overview of available support options, one contact for administrative issues, and an environment that pays attention to ICGs' wellbeing could make caregiving easier. Formal carers and digital tools can support caregivers in balancing wishes and boundaries with the requests of caregiving to decrease conflicts.</AbstractText
|
[
[
"38845595",
"Staying in control: Characterizing the mechanisms underlying cognitive control in high and low arousal states.",
"Throughout the day, humans show natural fluctuations in arousal that impact cognitive function. To study the behavioural dynamics of cognitive control during high and low arousal states, healthy participants performed an auditory conflict task during high-intensity physical exercise (N = 39) or drowsiness (N = 33). In line with the pre-registered hypotheses, conflict and conflict adaptation effects were preserved during both altered arousal states. Overall task performance was markedly poorer during low arousal, but not for high arousal. Modelling behavioural dynamics with drift diffusion analysis revealed evidence accumulation and non-decision time decelerated, and decisional boundaries became wider during low arousal, whereas high arousal was unexpectedly associated with a decrease in the interference of task-irrelevant information processing. These findings show how arousal differentially modulates cognitive control at both sides of normal alertness, and further validate drowsiness and physical exercise as key experimental models to disentangle the interaction between physiological fluctuations on cognitive dynamics.</AbstractText"
]
] |
[
[
"40132153",
"Neuroimaging in Children With Inherited Metabolic Epilepsies.",
"Inherited metabolic epilepsies (IMEs) represent inherited metabolic disorders in which seizures, various in types and typically intractable, are one of the predominant manifestations and primary determinants of the overall outcome. A metabolic etiology should be suspected in any case of refractory seizures stemming from an undetermined cause. While the occurrence rate of individual IMEs is rare, their cumulative prevalence is high enough to pose a significant clinical challenge. Concurrently with genetic and metabolic tests, neuroimaging is considered part of the first tier of their investigation, attained with an aim to affirm or counter the phenotype. It may be normal or nonspecific; however, as described by this overview, there is an appreciable number of IMEs associated with distinct MRI or magnetic resonance spectroscopy patterns. Apart from narrowing or supporting their diagnoses, these neuroimaging patterns may serve as biomarkers to monitor treatment efficacy and outcome. Other advanced modalities and techniques, such as PET, fMRI, diffusion tensor imaging, MRI g-ratio mapping, and functional near-infrared spectroscopy, broaden our insights relating to their pathophysiology, clinical course, targeted treatment development, and prognosis.</AbstractText"
]
] |
40492610
|
MDMA-assisted psychotherapy for AUD: Bayesian analysis of WHO drinking risk level and exploratory analysis of drinking behavior and psychosocial functioning at 3 months follow-up.
|
Safety and tolerability data from the first open-label feasibility study of 3,4-methylenedioxymethamphetamine (MDMA)-assisted psychotherapy for alcohol use disorder was recently published. This paper presents a Bayesian analysis of the impact of MDMA-assisted psychotherapy on treatment success, defined as 2-level reduction in the World Health Organization (WHO) drinking risk at the 3 months follow-up. We also examined the impact on drinking behavior and psychosocial measures at 3 months compared to baseline.</AbstractText Fourteen participants with a diagnosis of alcohol use disorder who had recently undergone detoxification completed an eight-week course of ten psychotherapy sessions, including two sessions with MDMA. Measures assessing drinking behavior, quality of life, sleep, self-compassion, and empathy were collected. Bayesian analysis using flat and skeptical priors was performed to determine treatment success defined as a 2-level reduction in WHO drinking risk.</AbstractText Bayesian analysis suggested that the probability of a 2-level reduction in WHO drinking risk from baseline to 3 months post-treatment is 55%-63%, based upon either a flat or skeptical prior respectively. We present preliminary findings suggesting reductions in alcohol craving (measured by the Penn Alcohol Craving Scale and Obsessive Compulsive Drinking Scale) and improvements in sleep and aspects of psychosocial functioning at 3 months follow-up compared to baseline.</AbstractText The Bayesian analysis provides a useful harm reduction endpoint interpretation of drinking in terms of a 2-level reduction in WHO drinking risk. Further findings provide preliminary insights into the potential impact of MDMA-assisted psychotherapy on quality of life and well-being in addition to reductions in drinking. ClinicalTrials.gov ID: NCT04158778.</AbstractText
|
[
[
"38619933",
"Suggesting a holistic framework for understanding healthcare services leadership competence - a critical interpretive synthesis.",
"Healthcare providers are under pressure due to increasing and more complex demands for services. Increased pressure on budgets and human resources adds to an ever-growing problem set. Competent leaders are in demand to ensure effective and well-performing healthcare organisations that deliver balanced results and high-quality services. Researchers have made significant efforts to identify and define determining competencies for healthcare leadership. Broad terms such as competence are, however, inherently at risk of becoming too generic to add analytical value. The purpose of this study is to suggest a holistic framework for understanding healthcare leadership competence, that can be crucial for operationalising important healthcare leadership competencies for researchers, decision-makers as well as practitioners.</AbstractText In the present study, a critical interpretive synthesis (CIS) was conducted to analyse competency descriptions for healthcare leaders. The descriptions were retrieved from peer reviewed empirical studies published between 2010 and 2022 that aimed to identify healthcare services leadership competencies. Grounded theory was utilised to code the data and inductively develop new categories of healthcare leadership competencies. The categorisation was then analysed to suggest a holistic framework for healthcare leadership competence.</AbstractText Forty-one papers were included in the review. Coding and analysing the competence descriptions resulted in 12 healthcare leadership competence categories: (1) character, (2) interpersonal relations, (3) leadership, (4) professionalism, (5) soft HRM, (6) management, (7) organisational knowledge, (8) technology, (9) knowledge of the healthcare environment, (10) change and innovation, (11) knowledge transformation and (12) boundary spanning. Based on this result, a holistic framework for understanding and analysing healthcare services leadership competencies was suggested. This framework suggests that the 12 categories of healthcare leadership competencies include a range of knowledge, skills and abilities that can be understood across the dimension personal - and technical, and organisational internal and - external competencies.</AbstractText This literature review was conducted with the results of searching only two electronic databases. Because of this, there is a chance that there exist empirical studies that could have added to the development of the competence categories or could have contradicted some of the descriptions used in this analysis that were assessed as quite harmonised. A CIS also opens for a broader search, including the grey literature, books, policy documents and so on, but this study was limited to peer-reviewed empirical studies. This limitation could also have affected the result, as complex phenomenon such as competence might have been disclosed in greater details in, for example, books.</AbstractText The holistic framework for healthcare leadership competences offers a common understanding of a \"fuzzy\" concept such as competence and can be used to identify specific competency needs in healthcare organisations, to develop strategic competency plans and educational programmes for healthcare leaders.</AbstractText This study reveals a lack of consensus regarding the use and understanding of the concept of competence, and that key competencies addressed in the included papers are described vastly different in terms of what knowledge, skills and abilities they entail. This challenges the operationalisation of healthcare services leadership competencies. The proposed framework for healthcare services leadership competencies offers a common understanding of work-related competencies and a possibility to analyse key leadership competencies based on a holistic framework.</AbstractText"
]
] |
[
[
"39955842",
"Hormones, brain and behavior in birds: The Lehrman legacy.",
"This short essay is based on the presentation I gave at the meeting of the Society of Behavioral Neuroendocrinology held in Tours, France in June 2023 when I received the Lehrman award for career achievement. I conducted my PhD at the Institute of Animal Behavior that was founded by Lehrman at Rutgers University. Although I never met Lehrman I was mentored by several scientists who had worked with him. I therefore decided to organize my essay about the Lehrman award around the enduring legacy of Lehrman's work as it influenced my career. Four aspects of the scientific legacy of Daniel Lehrman are distinguished and I discuss how these insights affected my own research program. A concise summary of the research I conducted in collaboration with PhD students and postdocs that relates to these topics is then presented. This research that involves several avian species includes studies of how behavior can influence the endocrine physiology and behavior of receivers of a particular signal. The cloning of the gonadotropin-releasing hormone (GnRH) gene in songbirds and analysis of the environmental factors influencing its expression demonstrated how the GnRH neuronal system is a key link between the perception of behavior and changes in endocrine physiology. Finally, there is a review of studies of the experimental analysis of the brain sites where testosterone acts to control the motivation to sing and the quality of song in songbirds that follow directly in the Lehrman line of work on how steroids regulate avian reproductive behaviors.</AbstractText"
]
] |
38412004
|
Characteristics of Hepatitis B Virus, Hepatitis C Virus, and Syphilis Coinfection in People With HIV/AIDS Contracted Through Different Sources: Retrospective Study.
|
The burden of hepatitis B virus (HBV), hepatitis C virus (HCV), and syphilis coinfections remains disproportionately high among people living with HIV/AIDS. Hubei province is located in central China, where there are distinct regional characteristics of the distribution of people living with HIV/AIDS acquired via diverse transmission routes and the AIDS epidemic itself.</AbstractText We aimed to estimate the magnitude of HBV, HCV, or syphilis coinfections among people living with HIV/AIDS with blood-borne transmission, which includes former paid blood donors, contaminated blood recipients, and intravenous drug users, as well as among people with sex-borne HIV transmission (including heterosexual people and men who have sex with men) and people with mother-to-child HIV transmission.</AbstractText From January 2010 to December 2020, people living with HIV/AIDS were tested for hepatitis B surface antigen (HBsAg), HCV antibodies, and syphilis-specific antibodies. The positive patients were further tested for HBV markers, HBV DNA, and HCV RNA, and received a rapid plasma reagin circle card test. All people living with HIV/AIDS were first divided into transmission groups (blood, sex, and mother-to-child); then, people with blood-borne HIV transmission were divided into former paid blood donors, contaminated blood recipients, and intravenous drug users, while people with sex-borne HIV transmission were divided into heterosexual people and men who have sex with men.</AbstractText Among 6623 people living with HIV/AIDS, rates of chronic HCV infection were 80.3% (590/735) in former paid blood donors, 73.3% (247/337) in intravenous drug users, 57.1% (444/777) in contaminated blood recipients, 19.4% (21/108) in people with mother-to-child HIV transmission, 8.1% (240/2975) in heterosexual people, and 1.2% (21/1691) in men who have sex with men. Chronic HBV infection rates were similar among all people with blood-borne HIV transmission. However, compared to heterosexual people, the chronic HBV infection rate was greater in men who have sex with men (213/1691, 12.6% vs 308/2975, 10.4%; χ<sup In people living with HIV/AIDS, HCV transmission intensity was significantly associated with specific exposure modes of blood or sexual contact. The rate of chronic HBV infection among men who have sex with men was higher than in any other population. Attention should be paid to the high prevalence of neurosyphilis in people living with HIV/AIDS who contract HIV by sexual intercourse.</AbstractText
|
[
[
"37795953",
"Diagnostic value of cerebrospinal fluid chemokine c-x-c motif ligand 13 for neurosyphilis: A systematic review and meta-analysis.",
"The diagnostic value of cerebrospinal fluid chemokine c-x-c motif ligand 13 (CSF CXCL13) for neurosyphilis was assessed by meta-analysis in this study. PubMed, Web of Science and Embase databases were searched to identify relevant articles by using MeSH and free terms of CXCL13 and neurosyphilis. A total of 720 syphilis and 338 neurosyphilis individuals in 6 articles were involved in this meta-analysis. The pooled sensitivity and specificity were 0.82 (95% confidence intervals (CI), 0.77-0.87) and 0.84 (95% CI, 0.79-0.87). The pooled positive likelihood ratio, negative likelihood ratio, diagnostic odds ratio and the area under receiver operating characteristic curve were 5.10 (95% CI, 3.90-6.60), 0.21 (95% CI, 0.16-0.28), 24.00 (95% CI, 14.00-39.00) and 0.88 (95% CI, 0.84-0.90), respectively. In subgroup analysis, human immunodeficiency virus infection and diagnostic criteria for neurosyphilis were identified to be associated with heterogeneity. Based on limited evidence, CSF CXCL13 can be helpful in diagnosing neurosyphilis.</AbstractText"
]
] |
[
[
"39391051",
"Deciphering Proteomic Expression in Inflammatory Disorders: A Mass Spectrometry Exploration Comparing Infectious, Noninfectious, and Traumatic Brain Injuries in Human Cerebrospinal Fluid.",
"The central nervous system (CNS) evokes a complex inflammatory response to injury. Inflammatory cascades are present in traumatic, infectious, and noninfectious disorders affecting the brain. It contains a mixture of pro- and anti-inflammatory reactions involving well-known proteins, but also numerous proteins less explored in these processes. The aim of this study was to explore the distinct inflammatory response in traumatic brain injury (TBI) compared with other CNS injuries by utilization of mass-spectrometry. In total, 56 patients had their cerebrospinal fluid (CSF) analyzed with the use of mass-spectrometry. Among these, CSF was collected via an external ventricular drain (EVD) from <i"
]
] |
40102551
|
Hair cortisol as a marker of stress in mild traumatic brain injury: a challenging measure.
|
Cortisol is released through activation of the hypothalamic-pituitary-adrenal axis by physiological and psychological stressors, such as mild traumatic brain injury (mTBI). This hormone is accumulated in hair over longer periods of time, reflecting both acute and chronic forms of stress, allowing for retrospective analyses within certain timeframes. The main objectives of this study were to analyze pre- and post-injury hair cortisol concentrations, and to explore possible associations with personality and recovery after mTBI. Hair samples of 61 mTBI patients were collected at 4-6 weeks post-injury and divided into pre- (1 cm) and post-injury (1 cm) segments. For comparison, hair samples of 24 age, sex and education matched healthy controls (HC) were collected and divided into similar segments. Cortisol was quantified using liquid chromatography-tandem mass spectrometry (LC-MS/MS). At two weeks post-injury, post-traumatic symptoms (PTS), emotional distress (anxiety/depression), and the personality trait neuroticism were measured. At six months post-injury, PTS and functional recovery (Glasgow Outcome Scale Extended) were determined. A significant increase in hair cortisol concentration from pre- to post-injury was found for both mTBI patients and HC, likely due to washout effects, with similar concentrations in both groups. Neither hair cortisol, nor the interaction with neuroticism, were associated with long-term PTS or functional recovery. Additionally, no differences in hair cortisol were observed between patients with a higher and lower risk of developing persistent PTS based on a modified Post-Concussion Symptoms Rule (PoCS Rule) including demographics, acute symptoms, pre-injury mental health and head CT. Altogether, our findings do not support the current use of hair cortisol as a potential marker of stress in mTBI.</AbstractText
|
[
[
"34054681",
"Traumatic Brain Injury Exposure Lowers Age of Cognitive Decline in AD and Non-AD Conditions.",
"We aimed to detect the possible accelerating role of previous traumatic brain injury (TBI) exposures on the onset of later cognitive decline assessed across different brain diseases. We analyzed data from the National Alzheimer's Coordinating Center (NACC), which provide information on history of TBI and longitudinal data on cognitive and non-cognitive domains for each available subject. At the time of this investigation, a total of 609 NACC subjects resulted to have a documented history of TBI. We compared subjects with and without a history of previous TBI (of any type) at the time of their first cognitive decline assessment, and termed them, respectively, TBI+ and TBI- subjects. Three hundred and sixty-one TBI+ subjects (229 male/132 female) and 248 TBI- subjects (156 male/92 female) were available. The analyses included TBI+ and TBI- subjects with a clinical diagnosis of Mild Cognitive Impairment, Alzheimer's disease, Dementia with Lewy bodies, Progressive supranuclear palsy, Corticobasal degeneration, Frontotemporal dementia, Vascular dementia, non-AD Impairment, and Parkinson's disease. The data showed that the mean age of TBI+ subjects was lower than TBI- subjects at the time of their first cognitive decline assessment (71.6 ± 11.2 vs. 74.8 ± 9.5 year; <i"
]
] |
[
[
"39333695",
"Exploring the structure and dynamics of soft and hard cuticle of Bombyx mori using solid-state NMR techniques.",
"This study conducts a comprehensive analysis and comparison of Bombyx mori cuticles across different developmental stages, ranging from larval to adult, utilizing advanced solid-state NMR techniques. The primary objective is to elucidate the underlying reasons for the contrasting hardness of adult cuticles and softness of larval cuticles. Notably, PXRD analysis reveals a prominent broad peak at 19.34°, indicating the predominantly amorphous nature of both larval and adult cuticles. Analysis of <sup"
]
] |
20883353
|
Identification of red-green colour deficiency: sensitivity of the Ishihara and American Optical Company (Hard, Rand and Rittler) pseudo-isochromatic plates to identify slight anomalous trichromatism.
|
Screening sensitivity, based on a specific number of errors, of the Ishihara plates and of the American Optical Company (Hardy, Rand and Rittler) plates (HRR plates) was determined by reviewing data obtained for 486 male anomalous trichromats identified and classified with the Nagel anomaloscope. Data were obtained for the 16 screening plates, with Transformation and Vanishing numeral designs, of the 38 plate Ishihara test, and for the four red-green screening plates (with six Vanishing designs) of the HRR test. Sensitivity of the Ishihara plates was found to be 97.7% on 4 errors and 98.4% on 3 errors. Only anomalous trichromats with slight deficiency, according to the anomaloscope matching range, made 8 errors or fewer. One screening error, a single missed figure, is normally allowed as a pass on the HRR test and 3 errors is often recommended as the fail criterion to eliminate false positive results. Twenty-three subjects made no error on the HRR screening plates and 12 subjects made a single error (35 anomalous trichromats). Screening sensitivity was therefore 92.8% using 2 errors as the fail criterion. Screening sensitivity was reduced to 87% when 3 errors was the fail criterion, and some deuteranomalous trichromats with moderate deficiency, according to the anomaloscope matching range, were not identified. Individuals who make a maximum of 2 errors on the HRR test, or on the Richmond HRR 4th Edition, should be re-examined with the Ishihara plates to determine their colour vision status. The present review confirms that the Ishihara test is a very sensitive screening test and identifies people with slight anomalous trichromatism. The HRR test is unsatisfactory for screening and should not be chosen solely for this purpose.</AbstractText
|
[
[
"15252758",
"Signatures of selection and gene conversion associated with human color vision variation.",
"Trichromatic color vision in humans results from the combination of red, green, and blue photopigment opsins. Although color vision genes have been the targets of active molecular and psychophysical research on color vision abnormalities, little is known about patterns of normal genetic variation in these genes among global human populations. The current study presents nucleotide sequence analyses and tests of neutrality for a 5.5-kb region of the X-linked long-wave \"red\" opsin gene (OPN1LW) in 236 individuals from ethnically diverse human populations. Our analysis of the recombination landscape across OPN1LW reveals an unusual haplotype structure associated with amino acid replacement variation in exon 3 that is consistent with gene conversion. Compared with the absence of OPN1LW amino acid replacement fixation since divergence from chimpanzee, the human population exhibits a significant excess of high-frequency OPN1LW replacements. Our results suggest that subtle changes in L-cone opsin wavelength absorption may have been adaptive during human evolution.</AbstractText"
]
] |
[
[
"20428887",
"The role of anterior insular cortex in social emotions.",
"Functional neuroimaging investigations in the fields of social neuroscience and neuroeconomics indicate that the anterior insular cortex (AI) is consistently involved in empathy, compassion, and interpersonal phenomena such as fairness and cooperation. These findings suggest that AI plays an important role in social emotions, hereby defined as affective states that arise when we interact with other people and that depend on the social context. After we link the role of AI in social emotions to interoceptive awareness and the representation of current global emotional states, we will present a model suggesting that AI is not only involved in representing current states, but also in predicting emotional states relevant to the self and others. This model also proposes that AI enables us to learn about emotional states as well as about the uncertainty attached to events, and implies that AI plays a dominant role in decision making in complex and uncertain environments. Our review further highlights that dorsal and ventro-central, as well as anterior and posterior subdivisions of AI potentially subserve different functions and guide different aspects of behavioral regulation. We conclude with a section summarizing different routes to understanding other people's actions, feelings and thoughts, emphasizing the notion that the predominant role of AI involves understanding others' feeling and bodily states rather than their action intentions or abstract beliefs.</AbstractText"
]
] |
28774650
|
Rapid anatomical brain imaging using spiral acquisition and an expanded signal model.
|
We report the deployment of spiral acquisition for high-resolution structural imaging at 7T. Long spiral readouts are rendered manageable by an expanded signal model including static off-resonance and B<sub
|
[
[
"11810678",
"Elimination of Nyquist ghosting caused by read-out to phase-encode gradient cross-terms in EPI.",
"Echo-planar imaging (EPI) commonly suffers from ghosting artifacts caused by zero- or first-order phase differences between the odd and even echoes that constitute an EPI dataset. Small-bore imaging systems with shielded gradients may suffer significantly from cross-term eddy currents due to the high degree of manufacturing precision required in such systems compared to larger whole-body coils. A Nyquist ghost caused by cross-term eddy current contributions from the read-out to the phase-encode axis was identified in a small-bore system and characterized using a modified EPI experiment and a computer simulation. The artifact was corrected for using both a postprocessing approach and compensation blips along the phase-encode axis. Correction using compensation blips proved to be a more effective strategy to reduce this artifact than the postprocessing method used.</AbstractText"
]
] |
[
[
"29872302",
"Valium without dependence? Individual GABA(A) receptor subtype contribution toward benzodiazepine addiction, tolerance, and therapeutic effects.",
"Benzodiazepines are one of the most prescribed medications as first-line treatment of anxiety, insomnia, and epilepsy around the world. Over the past two decades, advances in the neuropharmacological understanding of gamma aminobutyric acid (GABA)<sub"
]
] |
24711394
|
Homeostasis of functional maps in active dendrites emerges in the absence of individual channelostasis.
|
The maintenance of ion channel homeostasis, or channelostasis, is a complex puzzle in neurons with extensive dendritic arborization, encompassing a combinatorial diversity of proteins that encode these channels and their auxiliary subunits, their localization profiles, and associated signaling machinery. Despite this, neurons exhibit amazingly stereotypic, topographically continuous maps of several functional properties along their active dendritic arbor. Here, we asked whether the membrane composition of neurons, at the level of individual ion channels, is constrained by this structural requirement of sustaining several functional maps along the same topograph. We performed global sensitivity analysis on morphologically realistic conductance-based models of hippocampal pyramidal neurons that coexpressed six well-characterized functional maps along their trunk. We generated randomized models by varying 32 underlying parameters and constrained these models with quantitative experimental measurements from the soma and dendrites of hippocampal pyramidal neurons. Analyzing valid models that satisfied experimental constraints on all six functional maps, we found topographically analogous functional maps to emerge from disparate model parameters with weak pairwise correlations between parameters. Finally, we derived a methodology to assess the contribution of individual channel conductances to the various functional measurements, using virtual knockout simulations on the valid model population. We found that the virtual knockout of individual channels resulted in variable, measurement- and location-specific impacts across the population. Our results suggest collective channelostasis as a mechanism behind the robust emergence of analogous functional maps and have significant ramifications for the localization and targeting of ion channels and enzymes that regulate neural coding and homeostasis.</AbstractText
|
[
[
"12417672",
"Response of neurons in the lateral intraparietal area during a combined visual discrimination reaction time task.",
"Decisions about the visual world can take time to form, especially when information is unreliable. We studied the neural correlate of gradual decision formation by recording activity from the lateral intraparietal cortex (area LIP) of rhesus monkeys during a combined motion-discrimination reaction-time task. Monkeys reported the direction of random-dot motion by making an eye movement to one of two peripheral choice targets, one of which was within the response field of the neuron. We varied the difficulty of the task and measured both the accuracy of direction discrimination and the time required to reach a decision. Both the accuracy and speed of decisions increased as a function of motion strength. During the period of decision formation, the epoch between onset of visual motion and the initiation of the eye movement response, LIP neurons underwent ramp-like changes in their discharge rate that predicted the monkey's decision. A steeper rise in spike rate was associated with stronger stimulus motion and shorter reaction times. The observations suggest that neurons in LIP integrate time-varying signals that originate in the extrastriate visual cortex, accumulating evidence for or against a specific behavioral response. A threshold level of LIP activity appears to mark the completion of the decision process and to govern the tradeoff between accuracy and speed of perception.</AbstractText"
]
] |
[
[
"23893323",
"An atypical case of SCN9A mutation presenting with global motor delay and a severe pain disorder.",
"Erythromelalgia due to heterozygous gain-of-function SCN9A mutations usually presents as a pure sensory-autonomic disorder characterized by recurrent episodes of burning pain and redness of the extremities.</AbstractText We describe a patient with an unusual phenotypic presentation of gross motor delay, childhood-onset erythromelalgia, extreme visceral pain episodes, hypesthesia, and self-mutilation. The investigation of the patient's motor delay included various biochemical analyses, a comparative genomic hybridization array (CGH), electromyogram (EMG), and muscle biopsy. Once erythromelalgia was suspected clinically, the SCN9A gene was sequenced.</AbstractText The EMG, CGH, and biochemical tests were negative. The biopsy showed an axonal neuropathy and neurogenic atrophy. Sequencing of SCN9A revealed a heterozygous missense mutation in exon 7; p.I234T.</AbstractText This is a case of global motor delay and erythromelalgia associated with SCN9A. The motor delay may be attributed to the extreme pain episodes or to a developmental perturbation of proprioceptive inputs.</AbstractText"
]
] |
40056182
|
Review of 7T MRI imaging of pituitary microadenomas: are we there yet?
|
7T MRI imaging of the pituitary gland is an emerging technique. The purpose of this article is to review the current status of the 7T MRI of the pituitary gland, particularly in the context of pituitary microadenoma pathology. We will discuss technical challenges and parallel transmission opportunities.</AbstractText Follow-up study selection and data extraction were performed following PRISMA guidelines. We focused on diagnostic performance and acquisition protocols. Inclusion criteria were: MRI imaging studies of pituitary adenoma at 7T. Exclusion criteria were: Case reports and reviews; studies which did not report MRI protocols; surgical planning studies; studies focusing exclusively on macroadenomas for which ultra-high magnetic field imaging is less decisive than microadenomas in clinical practice.</AbstractText Six studies were included. 7T MRI outperformed 1.5 or 3T MRI for the detection of microadenomas. Acquisition protocols employed were heterogeneous, with two-dimensional T<sub 7T MRI is a promising tool for overcoming the difficulties encountered by conventional MRI, particularly in the case of Cushing disease. However, there is insufficient data to precisely define an optimal protocol yet.</AbstractText • 7T MRI outperforms conventional MRI in detecting microadenomas. • The increased in artifacts at 7T does not affect the interpretation of the data. • A reference protocol cannot be defined, given the heterogeneity of practices.</AbstractText
|
[
[
"19449383",
"A transmit/receive system for magnetic field monitoring of in vivo MRI.",
"Magnetic field monitoring with NMR probes has recently been introduced as a means of measuring the actual spatiotemporal magnetic field evolution during individual MR scans. Receive-only NMR probes as used thus far for this purpose impose significant practical limitations due to radiofrequency (RF) interference with the actual MR experiment. In this work these limitations are overcome with a transmit/receive (T/R) monitoring system based on RF-shielded NMR probes. The proposed system is largely autonomous and protected against RF contamination. As a consequence the field probes can be positioned freely and permit monitoring imaging procedures of arbitrary geometry and angulation. The T/R approach is also exploited to simplify probe manufacturing and remove constraints on material choices. Probe miniaturization permits monitoring imaging scans with nominal resolutions on the order of 400 microm. The added capabilities of the new probes and system are demonstrated by first in vivo results, obtained with monitored gradient-echo and spin-echo echo-planar imaging (EPI) scans.</AbstractText"
]
] |
[
[
"40503482",
"Magnetic resonance defecography assessment of obstructed defecation syndrome in patients with chronic constipation in a tertiary care hospital.",
"Obstructed defecation syndrome (ODS) is a subtype of constipation that is considered one of the major pelvic floor dysfunctions affecting the aging population, particularly women over 50 seeking medical care. The condition is characterized by the urge to defecate but an impaired ability to expel the fecal bolus. ODS is associated with various anorectal abnormalities, which are not always apparent during a standard physical examination, requiring specialized imaging techniques for proper diagnosis.</AbstractText To study the distribution of causes of ODS in patients with chronic constipation by magnetic resonance defecography (MRD).</AbstractText This observational study evaluated the causes of ODS in 57 patients with chronic constipation who presented to Bangabandhu Sheikh Mujib Medical University between July 2020 and June 2021. After obtaining institutional review board approval and informed consent, patients underwent history taking, physical exams, and relevant investigations. ODS was diagnosed using Rome III criteria, with colonoscopy ruling out organic causes. Standard MRD was performed in different phases, and images were analyzed by expert radiologists and reported in a standardized format.</AbstractText Pelvic floor descent and anorectal junction descent were the most frequent findings, each present in 94.7% of cases. Rectocele was observed in 78.9% of patients, while vaginal or uterine prolapse was seen in 59.4% of females. Less common abnormalities included paradoxical contraction (7%), and there were no cases of sigmoidocele. Functional measurements showed significant differences in pelvic floor dynamics between rest and defecation, particularly in the H-line, M-line, and descent of pelvic organs (<i Pelvic floor descent and anorectal descent were the most common findings in patients suffering from ODS, followed by rectocele. Younger females (< 30 years) were most affected.</AbstractText"
]
] |
40166768
|
Crossing the chasm: engaging Black men survivors of gun violence in mental health services.
|
Despite being high risk for post-traumatic stress disorder, Black men survivors of gun violence, and particularly young men aged 18-24, seldom participate in mental health services after injury. The aim of this study was to identify barriers to participation in mental health services for this population.</AbstractText Over a 2-year period, 1 hour-long focus group was conducted with three counselors of the local hospital-based violence intervention program and 21 individual, semistructured in-depth interviews were held with Black men who were hospitalized for a firearm-related injury. All interviews were recorded and transcribed. Transcripts were coded using open coding and grounded theory methodology and ultimately grouped into themes using MAXQDA V.2022 software.</AbstractText Median age of participants was 34 years (IQR=11). Barriers to participation revolved around competing priorities/stressors, expense, difficulty with trust and openness and the demands of street life. Motivating factors included cultural competence, persistence, availability, reliability and genuineness of the therapy staff. Most participants denied negative social stigma of therapy as a barrier but emphasized that the individual must value therapy to participate. Young, Black men were perceived as struggling with self and peer-imposed views of masculinity that conflicted with therapy participation.</AbstractText Black men who have experienced violent firearm injury face strong social pressures that conflict with participation in mental health services. Programs must be integrated with other social services and be responsive to community conditions to be successful.</AbstractText IV.</AbstractText
|
[
[
"25863813",
"Cerebellar Contribution to Context Processing in Extinction Learning and Recall.",
"Whereas acquisition of new associations is considered largely independent of the context, context dependency is a hallmark of extinction of the learned associations. The hippocampus and the prefrontal cortex are known to be involved in context processing during extinction learning and recall. Although the cerebellum has known functional and anatomic connections to the hippocampus and the prefrontal cortex, cerebellar contributions to context processing of extinction have rarely been studied. In the present study, we reanalyzed functional brain imaging data (fMRI) of previous work investigating context effects during extinction in a cognitive associative learning paradigm in 28 young and healthy subjects (Lissek et al. Neuroimage. 81:131-3, 2013). In that study, event-related fMRI analysis did not include the cerebellum. The 3 T fMRI dataset was reanalyzed using a spatial normalization method optimized for the cerebellum. Data of seven participants had to be excluded because the cerebellum had not been scanned in full. Cerebellar activation related to context change during extinction learning was most prominent in lobule Crus II bilaterally (p < 0.01, t > 2.53; partially corrected by predetermined cluster size). No significant cerebellar activations were observed related to context change during extinction retrieval. The posterolateral cerebellum appears to contribute to context-related processes during extinction learning, but not (or less) during extinction retrieval. The cerebellum may support context learning during extinction via its connections to the hippocampus. Alternatively, the cerebellum may support the shifting of attention to the context via its known connections to the dorsolateral prefrontal cortex. Because the ventromedial prefrontal cortex (vmPFC) is critically involved in context-related processes during extinction retrieval, and there are no known connections between the cerebellum and the vmPFC, the cerebellum may be less important during extinction recall.</AbstractText"
]
] |
[
[
"40412529",
"Surgical Nerve Decompression at Lower Extremity for Diabetic Neuropathy: A Systematic Review and Meta-Analysis of Time-Dependent Pain, Sensory Recovery, Amputation, Ulcer Recurrence, and Balance.",
"This systematic review and meta-analysis evaluated the efficacy of surgical nerve decompression in patients with diabetic peripheral neuropathy, focusing on pain relief over time, comprehensive sensory function, reduction in ulcer recurrence, amputation prevention, and balance improvement.</AbstractText Databases including PubMed, Scopus, and Web of Science were systematically searched up to January 8, 2025. Eighteen studies (4 randomized controlled trials and 14 observational studies; total n = 837) met inclusion criteria. Primary outcomes were pain relief and sensory recovery; secondary outcomes were ulcer recurrence, amputation rates, and balance. Data synthesis employed random-effects or fixed-effects models with heterogeneity and publication bias assessments.</AbstractText Surgical decompression significantly reduced pain at short-term (6 months: standardized mean difference [SMD]: 2.40, P < 0.001), medium-term (12 months: SMD: 2.02, P = 0.014), and long-term (> 12 months: SMD: 3.24, P = 0.009) follow-ups. Meta-regression revealed modest attenuation of pain relief over time (R<sup Surgical nerve decompression demonstrates sustained efficacy in pain management and substantially reduces severe diabetic neuropathy complications. Future high-quality randomized controlled trials are necessary to standardize outcomes and confirm long-term benefits.</AbstractText"
]
] |
39570907
|
Functional near-infrared spectrometry for auditory speech stimuli in cochlear implant users: a systematic literature review.
|
This study aims to identify the acquisition features of functional near-infrared spectroscopy (fNIRS) in cochlear implant users.</AbstractText A systematic literature review was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. PubMed, EMBASE, LILACS, Web of Science, Scopus, PsycINFO, IEEE Xplore, Google Scholar, and ProQuest Dissertations & Theses Global were searched using the PECOS acronym. Inclusion criteria encompassed studies involving fNIRS with speech stimuli in cochlear implant users of any age, with information on acquisition parameters and features. Risk of bias assessment was performed using the Joanna Briggs Institute tool.</AbstractText Nineteen studies were included, with thirteen exhibiting a low risk of bias. Noteworthy uniformity was observed in certain fNIRS acquisition features among cochlear implant users, including the waking state (awake), auditory stimuli of words or phrases presented in a free field, visual stimuli displayed during data collection as a secondary task, recording of responses in the bilateral temporal lobe, and a three-centimeter distance between optodes. Variations in acquisition were attributed to differing study purposes.</AbstractText This review identifies common acquisition characteristics for fNIRS in cochlear implant users. Multicenter research efforts are advocated to further advance the utility of fNIRS in this population.</AbstractText
|
[
[
"25151264",
"Dimensionality reduction for large-scale neural recordings.",
"Most sensory, cognitive and motor functions depend on the interactions of many neurons. In recent years, there has been rapid development and increasing use of technologies for recording from large numbers of neurons, either sequentially or simultaneously. A key question is what scientific insight can be gained by studying a population of recorded neurons beyond studying each neuron individually. Here, we examine three important motivations for population studies: single-trial hypotheses requiring statistical power, hypotheses of population response structure and exploratory analyses of large data sets. Many recent studies have adopted dimensionality reduction to analyze these populations and to find features that are not apparent at the level of individual neurons. We describe the dimensionality reduction methods commonly applied to population activity and offer practical advice about selecting methods and interpreting their outputs. This review is intended for experimental and computational researchers who seek to understand the role dimensionality reduction has had and can have in systems neuroscience, and who seek to apply these methods to their own data.</AbstractText"
]
] |
[
[
"38159612",
"Association Between Quality of Life and Neurogenic Bowel Symptoms by Bowel Management Program in Spina Bifida.",
"To compare differences in bowel-specific quality of life (QOL), overall qQOL, and neurogenic bowel dysfunction (NBD) severity by bowel management program in patients with spina bifida (SB).</AbstractText We performed a retrospective cross-sectional study of patients ≥12 years old at our multidisciplinary SB center who completed both a modified Peristeen NBD questionnaire (assessing bowel symptom severity and bowel-specific QOL) and the Patient-Reported Outcomes Measurement Information System Pediatric Global Health questionnaire (assessing overall QOL). Nested, multivariable models were fit for associations between outcomes and bowel management program (enemas, conservative management, and none).</AbstractText A total of 173 patients, 56.1% female and 64.6% with myelomeningocele, were included in our analysis. Median age was 18.2 years old. Patients reported using enemas (n = 42), conservative management (n = 63), and no bowel program (n = 68). When adjusting for covariates, there was no significant association between bowel-specific QOL nor overall QOL across bowel management programs. However, the use of conservative management compared to enemas was associated with worse bowel symptoms severity (adjusted beta=2.58, 95%CI=[0.09,5.06]). Additionally, greater bowel symptom severity was significantly associated with lower overall QOL (adjusted beta=-0.33, 95%CI=[-0.57,-0.10]).</AbstractText NBD symptom severity in SB is more strongly associated with QOL than the individual bowel program being utilized. Our findings suggest that different degrees of NBD require different invasiveness of bowel programs, but it is the outcome of the bowel management program and not the specific program itself that is most associated with QOL.</AbstractText"
]
] |
40715419
|
Inter- and intra-bacterial strain diversity remains the "elephant in the (living) room".
|
Acinetobacter baumannii is an opportunistic Gram-negative bacterial pathogen responsible for severe nosocomial infections worldwide. Resistance to last-resort antibiotics causes A. baumannii to be ranked as a top priority for the research and development of new antibiotics by the WHO and an urgent threat to public health by the CDC. It is also a member of the ESKAPE group comprising the most problematic antibiotic-resistant nosocomial pathogens. Resistance towards desiccation, disinfectants, reactive oxygen species, and the host immune system helps A. baumannii thrive in hospital settings and infect individuals compromised by lines, tubes, and indwelling devices. A. baumannii displays extensive genomic heterogeneity, yet recent studies show that this level of plasticity is also prevalent in lab strains widely used to study A. baumannii biology. Successive subculturing of widely used strains and spontaneous genetic variations results in significantly altered genotypes and phenotypes, often not recognized by the scientific community. In addition, the current strain designation methods do not allow efficient communication about such differences. Even presumably identical strains from established culture collections have been found to demonstrate genetic heterogeneity. The "elephant in the (living) room" refers to the risk but also the potential of the bi-partite problem concerning the high diversity amongst A. baumannii isolates (inter-strain variability), and the universal issue of microevolution (intra-strain variability). This is generally ignored as it is not referenced adequately in scientific publications. We aim to raise awareness about the current issues and the problematic consequences generated by intra- and inter-strain diversity based on modern examples of A. baumannii isolates. Therefore, this review provides cases of broadly used A. baumannii strains and their genetic and phenotypic differences.</AbstractText
|
[
[
"33495315",
"Inhibition of Hedgehog Signaling Alters Fibroblast Composition in Pancreatic Cancer.",
"Pancreatic ductal adenocarcinoma (PDAC) is a deadly disease characterized by an extensive fibroinflammatory stroma, which includes abundant cancer-associated fibroblast (CAF) populations. PDAC CAFs are heterogeneous, but the nature of this heterogeneity is incompletely understood. The Hedgehog pathway functions in PDAC in a paracrine manner, with ligands secreted by cancer cells signaling to stromal cells in the microenvironment. Previous reports investigating the role of Hedgehog signaling in PDAC have been contradictory, with Hedgehog signaling alternately proposed to promote or restrict tumor growth. In light of the newly discovered CAF heterogeneity, we investigated how Hedgehog pathway inhibition reprograms the PDAC microenvironment.</AbstractText We used a combination of pharmacologic inhibition, gain- and loss-of-function genetic experiments, cytometry by time-of-flight, and single-cell RNA sequencing to study the roles of Hedgehog signaling in PDAC.</AbstractText We found that Hedgehog signaling is uniquely activated in fibroblasts and differentially elevated in myofibroblastic CAFs (myCAF) compared with inflammatory CAFs (iCAF). Sonic Hedgehog overexpression promotes tumor growth, while Hedgehog pathway inhibition with the smoothened antagonist, LDE225, impairs tumor growth. Furthermore, Hedgehog pathway inhibition reduces myCAF numbers and increases iCAF numbers, which correlates with a decrease in cytotoxic T cells and an expansion in regulatory T cells, consistent with increased immunosuppression.</AbstractText Hedgehog pathway inhibition alters fibroblast composition and immune infiltration in the pancreatic cancer microenvironment.</AbstractText"
]
] |
[
[
"40413347",
"Type-1 Diabetes Impacts Brain Microstructure and Anatomical Associations in Young and Well-Controlled Individuals.",
"Type 1 Diabetes Mellitus (T1DM) progression has a direct impact on brain microstructural integrity and typical functional organization from the early stages of neurodevelopment. Diffusion Tensor Imaging (DTI) is a neuroimaging method that has proven sensitive to changes in white matter microstructure. Using diffusion-weighted probabilistic tractography methods, we aim to evaluate the white matter integrity and anatomical relationships within the Default Mode Network (DMN) brain regions, which have been proven to be particularly affected by T1DM in a group of eighteen carefully selected clinically well-controlled young T1DM patients versus eighteen healthy matched controls according to sex, age, and education level. Results showed no relevant differences in the anatomical distribution of DMN between the groups. However, the transitivity graph metric was significantly lower in T1DM patients, who also showed weaker connectivity between the left ventral prefrontal cortex and the left medial temporal gyrus, representing the anatomical trajectory of the arcuate fasciculus. Considering that neural myelination is affected by language input and the critical role of language-related structures on brain development, the current findings denote early ill-driven brain modifications to better adapt to the increasing daily demands.</AbstractText"
]
] |
40461172
|
Medical management of ADHD in adults: part 2.
|
Methylphenidate and lisdexamfetamine are recommended as first-line pharmacological treatment options for adults with attention deficit hyperactivity disorder (ADHD). Formulations of methylphenidate can generally be classified into three groups according to their duration of action: one group lasts 12 hours, another group lasts 8 hours and the immediate-release group lasts 3-4 hours. Patients are usually able to substitute brands with one of the equivalent release profiles without significant problems. Lisdexamfetamine is a prodrug which has a slow onset and long duration (approximately 12 hours), ensuring minimal potential for abuse compared with its active metabolite dexamfetamine. Second-line treatments such as atomoxetine are also available for those who cannot tolerate or do not respond to methylphenidate or lisdexamfetamine. In the UK, ADHD has been previously managed largely in tertiary clinics, but many cases could be managed by appropriately trained clinicians in secondary or primary care (as already happens in some countries), with great benefit for patients and job satisfaction for clinicians.</AbstractText
|
[
[
"39376970",
"Relationships between screen time and childhood attention deficit hyperactivity disorder: a Mendelian randomization study.",
"In previous observational studies and meta-analyses, childhood attention deficit hyperactivity disorder (ADHD) is found to have a significant association with screen time. However, the causal associations between them remain unclear.</AbstractText This study performed a bidirectional two-sample Mendelian randomization (MR) analysis to confirm the causality between screen time and childhood ADHD. Large-scale genome-wide association studies (GWAS) datasets derived from the Psychiatric Genomics Consortium (PGC) and the UK Biobank were used to identify single nucleotide polymorphisms (SNPs) associated with exposure and outcome. Four categories of datasets were selected to represent screen time. The SNPs that are significantly associated with exposure data (P < 5e-08) and have a strong correlation with the exposure in the F-statistic (F > 10) were selected as instrumental variables. This study also used the PhenoScanner V2 database and the LDlink webtool to exclude confounding factors, and the MR-PRESSO method (p < 0.05) was employed to eliminate outliers with bias. Five commonly used methods were employed to assess the interaction and the Inverse Variance Weighted (IVW) method was utilized as the primary basis for determining the MR estimates in this study.</AbstractText The MR analysis revealed that the length of mobile phone use (OR, 1.848; 95% CI, 1.3360-2.5558; p=2.07e-4) and the time spent watching television (OR, 2.104; 95% CI, 1.3958-3.1703; p=3.8e-4) increased the risk of childhood ADHD. Although the causal relationships were exclusively identified through the IVW and weighted median methods, the results retained their statistical significance following correction. In the reverse analysis, no evidence was found to support an effect of childhood ADHD on screen time. The sensitivity analysis conducted on the significant findings revealed no evidence of horizontal pleiotropy or heterogeneity.</AbstractText This study provides some evidence for the causality of screen time and childhood ADHD. Given the limitations of our study, further research is required to comprehensively investigate this relationship.</AbstractText"
]
] |
[
[
"40737393",
"The β(2)-adrenergic receptor (Adrb2) entrains circadian gene oscillation and CD8(+) T cell differentiation in response to virus infection.",
"Adaptive immune cells are regulated by circadian rhythms both under steady state conditions and during responses to infection. Cytolytic CD8<sup"
]
] |
39853319
|
Neural mechanisms of behavioral addiction: An ALE meta-analysis and MACM analysis.
|
Behavioral addictions (BAs) represent complex and multifaceted disorders often associated with maladaptive neural alteration. To deepen our understanding of the essence of BAs, this study focuses on the neural mechanisms underlying its three stages: reward seeking, self-control, and decision-making. The aim of the current meta-analysis is to investigate the brain regions and neural networks involved in BAs.</AbstractText Adhering to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, we systematically searched for relevant articles published before September 1, 2024, in the Web of Science and PubMed databases, and supplemented our search with Google Scholar. We conducted analyses using activation likelihood estimation (ALE) meta-analysis and meta-analytic connectivity modeling (MACM) analyses.</AbstractText A total of 50 functional magnetic resonance imaging studies involving 906 participants were included. The findings showed that individuals with BAs exhibited hyperactivation in the right inferior frontal gyrus (IFG), bilateral caudate and left middle frontal gyrus (MFG), and a high degree of connectivity was found between the right caudate, left caudate, and right IFG. These findings indicated that BAs were associated with the fronto-striatal circuits. Individuals with BAs demonstrate specific neural activation patterns in the reward seeking, self-control, and decision-making stages, characterized by differences in activation and functional connectivity of brain regions associated with these stages.</AbstractText This study verifies the pivotal role of the fronto-striatal circuits in BAs and highlights the specific patterns of brain activity in different stages of addictive behavior. These findings expand our understanding of neural mechanisms underlying BAs and supports and provide partial support for the I-PACE model.</AbstractText
|
[
[
"26802508",
"A failure of suppression within the default mode network in depressed adolescents with compulsive internet game play.",
"Individuals who are chronic, compulsive video game players experience an elevated incidence of major depression. Excessive or problematic game play can interact with depression clinically, and may magnify impulsive behavior associated with video gaming.</AbstractText Functional brain imaging was performed during a Wisconsin Card Sorting Test (WCST) task in 42 healthy control and 95 volunteers seeking treatment for compulsive video game playing, including 60 participants without major depression (pure internet gaming disorder, pure IGD) and 35 participants comorbid with major depression (IGD+MDD).</AbstractText In response to the WCST in contrast to fixation, activation was observed in canonical brain attentional networks including bilateral intraparietal sulcus, frontal eye fields, and middle temporal cortical regions as well as dorsolateral prefrontal, inferior parietal and anterior insula, anterior cingulate cortex in all participants. For WCST>Fixation contrasts, the IGD+MDD group exhibited greater relative activation within the left hippocampus, compared to healthy control participants. For WCST>Fixation contrasts, the IGD+MDD group exhibited greater relative activation within the left hippocampus and the right parahippocampal gyrus immediately posterior to the hippocampus, compared to the pure IGD group.</AbstractText In cohorts of individuals with a history of compulsive internet game play, individuals with depression showed failure to suppress default mode network activity during an attentionally demanding task, compared to individuals without depression, including comparison groups with and without a history of compulsive video gaming. This reduced suppression of the brain regions within the default mode network may be a consequence of depressive neurophysiology or represent a predisposition for depression within compulsive game players.</AbstractText"
]
] |
[
[
"39804020",
"Step Width Haptic Feedback for Gait Stability in Spinocerebellar Ataxia: Preliminary Results.",
"Wider step width and lower step-to-step variability are linked to improved gait stability and reduced fall risk. It is unclear if patients with spinocerebellar ataxia (SCA) can learn to adjust these aspects of gait to reduce fall risk.</AbstractText The aims were to examine the possibility of using wearable step width haptic biofeedback to enhance gait stability and reduce fall risk in individuals with SCA.</AbstractText Thirteen people with SCA type 3 performed step width training (single session) using real-time feedback.</AbstractText Step width increased post-training (19.3 cm, interquartile range [IQR] 16.3-20.2 cm) and at retention (16.6 cm, IQR 16.2-21.1 cm), compared to baseline (11.0 cm, IQR 5.2-15.2 cm; P < 0.001). Step width variability decreased during post-training (19.7%, IQR 17.4%-26.2%) and at retention (22.3%, IQR 18.6%-30.2%), compared to baseline (44.5%, IQR 28.5%-71.2%; P < 0.001). Crossover steps, another mark of instability, decreased after training (P < 0.031).</AbstractText These pilot results suggest that patients with SCA can use a novel, wearable biofeedback system to improve their gait stability. © 2025 International Parkinson and Movement Disorder Society.</AbstractText"
]
] |
29471227
|
The impact of acute and short-term methamphetamine abstinence on brain metabolites: A proton magnetic resonance spectroscopy chemical shift imaging study.
|
Abuse of methamphetamine (MA) is a global health concern. Previous <sup Adults with chronic MA dependence (n = 31) and healthy controls (n = 22) were recruited. Two-dimensional chemical shift <sup Acute MAA showed lower n-acetyl-aspartate (NAA) and n-acetyl-aspartate with n-acetyl-aspartyl-glutamate (NAA + NAAG) in left DLPFC, and glycerophosphocholine with phosphocholine (GPC + PCh) in left FWM. Short-term MAA showed lower NAA + NAAG and higher myo-inositol (mI) in right ACC, lower NAA and NAA + NAAG in the left DLPFC, and lower GPC + PCh in left FWM. Over time, MAA showed decreased NAA and NAA + NAAG and increased mI in right ACC, decreased NAA and NAA + NAAG in right FWM, and decreased in mI in left FWM.</AbstractText In acute MAA, there was damage to the integrity of neuronal tissue, which was enhanced with short-term MAA. From acute to short-term MAA, activation of neuroinflammatory processes are suggested. This is the first <sup
|
[
[
"24897622",
"μHigh resolution-magic-angle spinning NMR spectroscopy for metabolic phenotyping of Caenorhabditis elegans.",
"Analysis of model organisms, such as the submillimeter-size Caenorhabditis elegans, plays a central role in understanding biological functions across species and in characterizing phenotypes associated with genetic mutations. In recent years, metabolic phenotyping studies of C. elegans based on (1)H high-resolution magic-angle spinning (HR-MAS) nuclear magnetic resonance (NMR) spectroscopy have relied on the observation of large populations of nematodes, requiring labor-intensive sample preparation that considerably limits high-throughput characterization of C. elegans. In this work, we open new platforms for metabolic phenotyping of C. elegans mutants. We determine rich metabolic profiles (31 metabolites identified) from samples of 12 individuals using a (1)H NMR microprobe featuring high-resolution magic-angle coil spinning (HR-MACS), a simple conversion of a standard HR-MAS probe to μHR-MAS. In addition, we characterize the metabolic variations between two different strains of C. elegans (wild-type vs slcf-1 mutant). We also acquire a NMR spectrum of a single C. elegans worm at 23.5 T. This study represents the first example of a metabolomic investigation carried out on a small number of submillimeter-size organisms, demonstrating the potential of NMR microtechnologies for metabolomics screening of small model organisms.</AbstractText"
]
] |
[
[
"29905724",
"Energy density and energy flux in the focus of an optical vortex: reverse flux of light energy.",
"Using the Richards-Wolf formulas for an arbitrary circularly polarized optical vortex with an integer topological charge m, we obtain explicit expressions for all components of the electric and magnetic field strength vectors near the focus, as well as expressions for the intensity (energy density) and for the energy flux (components of the Poynting vector) in the focal plane of an aplanatic optical system. For m=2, from the obtained expressions it follows that the energy flux near the optical axis propagates in the reversed direction, rotating along a spiral around the optical axis. On the optical axis itself, the reversed flux is maximal and decays rapidly with the distance from the axis. For m=3, in contrast, the reversed energy flux in the focal plane is minimal (zero) on the optical axis and increases (until the first ring of the light intensity) as a squared distance from the axis.</AbstractText"
]
] |
40385881
|
Post-thalamotomy Changes Mimicking Cavernous Malformations on MRI: A Case Report of a Historical Surgical Treatment.
|
The patient was a 65-year-old man with cervical dystonia onset at age six who had been treated at Chiba University Hospital. He was diagnosed and followed up with cavernous malformations and chronic cerebral infarctions based on an MRI. However, during the re-evaluation of MRI, lesions with low signal intensity (SI) cores surrounded by high SI rims were observed in bilateral thalami and left subthalamic nucleus on T2-weighted images, which differed from typical cavernous malformations. In addition, symmetrical scarring changes were noted in the frontal lobes and bilateral parietal bones, potentially corresponding to the thalamic and subthalamic nucleus lesions. Upon reviewing medical history, it was revealed that the patient had undergone thalamotomy in 1963 and 1964. The literature review suggested the use of procaine-oil blocking during thalamotomies of that era. Chemical shift imaging was added, and the presence of fat was confirmed in bilateral thalamic lesions with high SI on in-phase and low SI on out-of-phase images. Imaging findings resulting from obsolete treatments can be unfamiliar and mistaken for pathological conditions. Investigating the history of suspected treatments can lead to definitive diagnoses through imaging studies.</AbstractText
|
[
[
"21666131",
"Abnormal structure-function relationship in spasmodic dysphonia.",
"Spasmodic dysphonia (SD) is a primary focal dystonia characterized by involuntary spasms in the laryngeal muscles during speech production. Although recent studies have found abnormal brain function and white matter organization in SD, the extent of gray matter alterations, their structure-function relationships, and correlations with symptoms remain unknown. We compared gray matter volume (GMV) and cortical thickness (CT) in 40 SD patients and 40 controls using voxel-based morphometry and cortical distance estimates. These measures were examined for relationships with blood oxygen level-dependent signal change during symptomatic syllable production in 15 of the same patients. SD patients had increased GMV, CT, and brain activation in key structures of the speech control system, including the laryngeal sensorimotor cortex, inferior frontal gyrus (IFG), superior/middle temporal and supramarginal gyri, and in a structure commonly abnormal in other primary dystonias, the cerebellum. Among these regions, GMV, CT and activation of the IFG and cerebellum showed positive relationships with SD severity, while CT of the IFG correlated with SD duration. The left anterior insula was the only region with decreased CT, which also correlated with SD symptom severity. These findings provide evidence for coupling between structural and functional abnormalities at different levels within the speech production system in SD.</AbstractText"
]
] |
[
[
"40446445",
"Optimizing mesenchymal stromal cells priming strategies for tailored effects on the secretome.",
"Mesenchymal stromal cells (MSCs) have emerged as a promising tool in regenerative medicine, with recent focus shifting towards their secretome as a cell-free therapeutic approach. This study investigates the impact of various priming strategies on the immunomodulatory, anti-inflammatory, and regenerative potential of adipose-derived MSCs (ASCs) secretomes. We evaluated the effects of hypoxia, pro-inflammatory cytokines, and spheroid culture conditions on ASC secretome composition and functionality. Gene expression analysis, nanoparticle tracking, protein quantification, and functional assays were performed to characterize the secretomes. RNA sequencing revealed significant differences in gene expression profiles across priming conditions, particularly in pathways related to osteogenesis, angiogenesis, inflammation, and neurotrophic factors. Notably, spheroid culture combined with hypoxia and inflammation resulted in a substantial increase in extracellular vesicle production and altered protein content. Functional assays demonstrated enhanced neutrophil inhibition by secretomes from hypoxia-primed ASCs. Our findings indicate that tailored priming strategies can significantly modulate the therapeutic properties of ASC secretomes, potentially enhancing their efficacy in various clinical applications. This study provides valuable insights for optimizing cell-free therapies in regenerative medicine and offers a basis for developing more targeted and effective treatments.</AbstractText"
]
] |
35317746
|
Comparative study of vestibular projection pathway connectivity in cerebellar injury patients and healthy adults.
|
Cerebellar injury can not only cause gait and postural instability, nystagmus, and vertigo but also affect the vestibular system. However, changes in connectivity regarding the vestibular projection pathway after cerebellar injury have not yet been reported. Therefore, in the current study, we investigated differences in the connectivity of the vestibular projection pathway after cerebellar injury using diffusion tensor imaging (DTI) tractography.</AbstractText We recruited four stroke patients with cerebellar injury. Neural connectivity in the vestibular nucleus (VN) of the pons and medulla oblongata in patients with cerebellar injury was measured using DTI. Connectivity was defined as the incidence of connection between the VN on the pons and medulla oblongata and target brain regions such as the cerebellum, thalamus, parieto-insular vestibular cortex (PIVC), and parietal lobe.</AbstractText At thresholds of 10 and 30, there was lower connectivity in the ipsilateral hemisphere between the VN at the medullar level and thalamus in the patients than in healthy adults. At a threshold of 1 and 10, the patient group showed lower VN connectivity with the PIVC than healthy adults. At a threshold of 1, VN connectivity with the parietal lobe in the contralateral hemisphere was lower in the patients than in healthy adults. Additionally, at a threshold of 30, VN connectivity at the pons level with the cerebellum was lower in healthy adults than in the patients.</AbstractText Cerebellar injury seems to be associated with decreased vestibular projection pathway connectivity, especially in the ipsilateral thalamus, PIVC, and contralateral parietal lobe.</AbstractText
|
[
[
"29129392",
"Targeting Obesity and Cachexia: Identification of the GFRAL Receptor-MIC-1/GDF15 Pathway.",
"Macrophage inhibitory cytokine-1/growth differentiation factor 15 (MIC-1/GDF15) is a divergent transforming growth factor (TGFβ) superfamily cytokine implicated in biological and disease processes including metabolism, cancer, and chronic inflammation, but whose receptor has remained elusive. Four laboratories have recently identified GFRAL, an orphan receptor of the glial-derived neurotrophic factor (GDNF) receptor α family, as the receptor for MIC-1/GDF15, signaling though the coreceptor Ret. These data identify a new systemic to central nervous system (CNS) circuit that regulates metabolism in response to stress and which could be targeted to treat both severe obesity and anorexia/cachexia syndrome.</AbstractText"
]
] |
[
[
"34449006",
"Exploring the Concept of Spiritual Sensitivity from the Perspectives of Healthcare Providers in Iran.",
"Spiritual sensitivity (SS) is defined as attention to the available spiritual values in a conflicting situation and awareness of one's roles and responsibilities in that situation. It helps differentiate between the right and the wrong and leads to sound practice. This study explored the concept of SS from the perspectives of healthcare providers in Iran. This qualitative study was carried out in 2017-2019 using conventional content analysis. Twenty-two physicians, faculty members with clinical work experience, and healthcare providers were purposefully recruited. Data were collected using unstructured interviews and were analyzed using conventional content analysis. Participants' experiences of the concept of SS were grouped into three main themes, namely sense of value, spiritual growth and morale boosting, and SS as a motivator for purposeful service delivery. The findings of the present study will help healthcare managers develop programs for improving healthcare providers' spiritual sensitivity and also will help healthcare providers develop spirituality-based holistic care plans.</AbstractText"
]
] |
37437821
|
LPS priming before plaque deposition impedes microglial activation and restrains Aβ pathology in the 5xFAD mouse model of Alzheimer's disease.
|
Microglia have an innate immunity memory (IIM) with divergent functions in different animal models of neurodegenerative diseases, including Alzheimer's disease (AD). AD is characterized by chronic neuroinflammation, neurodegeneration, tau tangles and β-amyloid (Aβ) deposition. Systemic inflammation has been implicated in contributing to the progression of AD. Multiple reports have demonstrated unique microglial signatures in AD mouse models and patients. However, the proteomic profiles of microglia modified by IIM have not been well-documented in an AD model. Therefore, in the present study, we investigate whether lipopolysaccharide (LPS)-induced IIM in the pre-clinical stage of AD alters the microglial responses and shapes the neuropathology. We accomplished this by priming 5xFAD and wild-type (WT) mice with an LPS injection at 6 weeks (before the robust development of plaques). 140 days later, we evaluated microglial morphology, activation, the microglial barrier around Aβ, and Aβ deposition in both 5xFAD primed and unprimed mice. Priming induced decreased soma size of microglia and reduced colocalization of PSD95 and Synaptophysin in the retrosplenial cortex. Priming appeared to increase phagocytosis of Aβ, resulting in fewer Thioflavin S<sup
|
[
[
"27766433",
"Midbrain Synchrony to Envelope Structure Supports Behavioral Sensitivity to Single-Formant Vowel-Like Sounds in Noise.",
"Vowels make a strong contribution to speech perception under natural conditions. Vowels are encoded in the auditory nerve primarily through neural synchrony to temporal fine structure and to envelope fluctuations rather than through average discharge rate. Neural synchrony is thought to contribute less to vowel coding in central auditory nuclei, consistent with more limited synchronization to fine structure and the emergence of average-rate coding of envelope fluctuations. However, this hypothesis is largely unexplored, especially in background noise. The present study examined coding mechanisms at the level of the midbrain that support behavioral sensitivity to simple vowel-like sounds using neurophysiological recordings and matched behavioral experiments in the budgerigar. Stimuli were harmonic tone complexes with energy concentrated at one spectral peak, or formant frequency, presented in quiet and in noise. Behavioral thresholds for formant-frequency discrimination decreased with increasing amplitude of stimulus envelope fluctuations, increased in noise, and were similar between budgerigars and humans. Multiunit recordings in awake birds showed that the midbrain encodes vowel-like sounds both through response synchrony to envelope structure and through average rate. Whereas neural discrimination thresholds based on either coding scheme were sufficient to support behavioral thresholds in quiet, only synchrony-based neural thresholds could account for behavioral thresholds in background noise. These results reveal an incomplete transformation to average-rate coding of vowel-like sounds in the midbrain. Model simulations suggest that this transformation emerges due to modulation tuning, which is shared between birds and mammals. Furthermore, the results underscore the behavioral relevance of envelope synchrony in the midbrain for detection of small differences in vowel formant frequency under real-world listening conditions.</AbstractText"
]
] |
[
[
"36808307",
"Neurobiological correlates and attenuated positive social intention attribution during laughter perception associated with degree of autistic traits.",
"Laughter plays an important role in group formation, signaling social belongingness by indicating a positive or negative social intention towards the receiver. In adults without autism, the intention of laughter can be correctly differentiated without further contextual information. In autism spectrum disorder (ASD), however, differences in the perception and interpretation of social cues represent a key characteristic of the disorder. Studies suggest that these differences are associated with hypoactivation and altered connectivity among key nodes of the social perception network. How laughter, as a multimodal nonverbal social cue, is perceived and processed neurobiologically in association with autistic traits has not been assessed previously. We investigated differences in social intention attribution, neurobiological activation, and connectivity during audiovisual laughter perception in association with the degree of autistic traits in adults [N = 31, M<sub"
]
] |
36770411
|
Towards the Standardization of Photothermal Measurements of Iron Oxide Nanoparticles in Two Biological Windows.
|
A systematic study on laser-induced heating carried out in two biological windows (800 nm and 1053 nm) for Fe<sub
|
[
[
"34411327",
"The Coax Dipole: A fully flexible coaxial cable dipole antenna with flattened current distribution for body imaging at 7 Tesla.",
"The coax dipole antenna, a flexible antenna for body imaging at 7T is presented. Similar to the high impedance coil, this coaxial cable antenna is fed on the central conductor and through gaps in the shield, the current passes to the outside of the antenna to generate B<sub Finite difference time domain (FDTD) simulations are performed to optimize the positions of the gaps in the shield for a flat current profile. Lumped inductors are added to each end to reduce losses. The performance of a single antenna is compared to a fractionated dipole using B<sub An optimal configuration is found with gaps located at 10 cm from the center and inductor values of 28 nH. In comparison to the fractionated dipole antenna, in single antenna phantom measurements the coax dipole achieves similar B<sub The coax dipole is a novel antenna design with a flattened current distribution resulting in beneficial properties. Also, the flexible design of the coax dipoles allows better adaptation to the body curvature and can potentially be used for a wide range of imaging targets.</AbstractText"
]
] |
[
[
"37738741",
"Cell-specific alterations in autophagy-lysosomal activity near the chronically implanted microelectrodes.",
"Intracortical microelectrodes that can record and stimulate brain activity have become a valuable technique for basic science research and clinical applications. However, long-term implantation of these microelectrodes can lead to progressive neurodegeneration in the surrounding microenvironment, characterized by elevation in disease-associated markers. Dysregulation of autophagy-lysosomal degradation, a major intracellular waste removal process, is considered a key factor in the onset and progression of neurodegenerative diseases. It is plausible that similar dysfunctions in autophagy-lysosomal degradation contribute to tissue degeneration following implantation-induced focal brain injury, ultimately impacting recording performance. To understand how the focal, persistent brain injury caused by long-term microelectrode implantation impairs autophagy-lysosomal pathway, we employed two-photon microscopy and immunohistology. This investigation focused on the spatiotemporal characterization of autophagy-lysosomal activity near the chronically implanted microelectrode. We observed an aberrant accumulation of immature autophagy vesicles near the microelectrode over the chronic implantation period. Additionally, we found deficits in autophagy-lysosomal clearance proximal to the chronic implant, which was associated with an accumulation of autophagy cargo and a reduction in lysosomal protease level during the chronic period. Furthermore, our evidence demonstrates reactive astrocytes have myelin-containing lysosomes near the microelectrode, suggesting its role of myelin engulfment during acute implantation period. Together, this study sheds light on the process of brain tissue degeneration caused by long-term microelectrode implantation, with a specific focus on impaired intracellular waste degradation.</AbstractText"
]
] |
37954642
|
Case series: Intraoperative neuromonitoring and angiography in the surgical treatment of vascular malformations.
|
In the surgical treatment of cerebral vascular malformations, e.g., aneurysms and arteriovenous malformations, the risk of ischemic complications is 6.7%, and a residual aneurysm is possible in 5.2% of these cases. Ischemic lesions can result in permanent neurological deficits, and a residual aneurysm can lead to the recurrence of the aneurysm in 2% of cases. In this article, we present five cases (two cases of ruptured aneurysms, two cases of non-ruptured aneurysms, and a case of arteriovenous malformation) in which we reduced the aforementioned risks with the use of intraoperative neuromonitoring and angiography. Intraoperative neuromonitoring (IONM) is used to measure motor and sensory-evoked potentials to detect brain hypoperfusion. Intraoperative angiography with the dye indocyanine green (ICG-A), which fluoresces in a vessel under a microscope after intravenous administration, helps to identify residual aneurysm sacs and distal blood flow. With the use of IONM and ICG-A, we identified abnormalities and adjusted our interventions and treatments. IONM and ICG-A can lead to a better outcome after surgical treatment of cerebral vascular abnormalities.</AbstractText
|
[
[
"25624933",
"Scalp arteriovenous malformations in young.",
"Scalp arteriovenous malformations are an exceptional group of vascular lesions with curious presentations and an elusive natural history. Their detection in the pediatric population is a rarer occurrence. We discuss our experience with five children suffering from this pathology and their surgical management carried at our institution from 2007 to 2013. The genesis in pediatric patients is, usually, spontaneous in contrast with the history of trauma seen in adults. Clinical symptoms, usually, range from an asymptomatic lesion, local discomfort, headaches to necrosis and massive hemorrhage. Selective angiography remains the cornerstone for investigation. Complete surgical excision, embolization or an approach combining the modalities is curative.</AbstractText"
]
] |
[
[
"36427671",
"The functional connectivity between left insula and left medial superior frontal gyrus underlying the relationship between rumination and procrastination.",
"Procrastination is regarded as a prevalent problematic behavior that impairs people's physical and mental health. Although previous studies have indicated that trait rumination is robustly positively correlated with procrastination, it remains unknown about the neural substrates underlying the relationship between trait rumination and procrastination. To address this issue, we used voxel-based morphometry (VBM) and resting-state functional connectivity (RSFC) approaches to explore the neural basis of the relationship between trait rumination and procrastination. Our behavior results found that trait rumination was significantly positively correlated to procrastination, while the VBM analysis showed that trait rumination was negatively correlated with gray matter volume of the insula. Furthermore, the RSFC results revealed a negative association of the left insula-lmSFG (left medial superior frontal gyrus) functional connectivity with trait rumination. More importantly, the mediation analysis showed that trait rumination could completely mediate the relationship between left insula-lmSFG functional connectivity and procrastination. These results suggest that the left insula-lmSFG functional connectivity involved in emotion regulation modulates the association between trait rumination and procrastination, which provides neural evidence for the relationship between trait rumination and procrastination.</AbstractText"
]
] |
40396767
|
Case series of CT-fusion and real-time US-guidance in percutaneous RF thermocoagulation for trigeminal rhizotomy.
|
This case series evaluates the feasibility, safety, and efficacy of real-time computed tomography fusion with ultrasound guidance (CTF-USG) in percutaneous radiofrequency thermocoagulation (RFT) for trigeminal rhizotomy. Traditional imaging modalities such as CT and fluoroscopy lack real-time visualization, increasing the risk of vascular injury and reducing procedural precision. The CTF-USG technique integrates CT imaging with real-time ultrasound via electromagnetic tracking, enabling accurate needle navigation and anatomical confirmation. Six patients with refractory trigeminal neuralgia affecting the V2 or V3 divisions underwent RFT guided by CTF-USG. All procedures achieved first-attempt needle placement success with no immediate complications. Postoperative assessments demonstrated significant reductions in pain scores at one and three months. The real-time imaging capability facilitated avoidance of critical structures, enhanced procedural safety. In conclusion, CTF-USG offers real-time imaging superior to C-arm fluoroscopy or standard CT, reducing complications and improving procedural accuracy. Primary technique efficacy was 100%. These advantages support its adoption in treating refractory trigeminal neuralgia.</AbstractText <b
|
[
[
"17274022",
"Dissociation of response inhibition and performance monitoring in the stop signal task using event-related fMRI.",
"We examined the neural substrate of motor response inhibition and performance monitoring in the stop signal task (SST) using event-related functional magnetic resonance imaging (fMRI). The SST involves a go task and the occasional requirement to stop the go response. We posit that both the go and the stop phases of the SST involve components of inhibition and performance monitoring. The goal of this study was to determine whether inhibition and performance monitoring during go and stop phases of the task activated different networks. We isolated go-phase activities underlying response withholding, monitoring, and sensorimotor processing and contrasted these with successful inhibition to identify the substrate of response inhibition. Error detection activity was isolated using trials in which a stop signal appeared but the response was executed. These trials were modeled as a hand-specific go trial followed by error processing. Cognitive go-phase processes included response withholding and monitoring and activated right prefrontal and midline networks. Response withdrawal additionally activated right inferior frontal gyrus and basal ganglia (caudate). Error detection invoked by failed inhibition activated dorsal anterior cingulate cortex (dACC) and right middle frontal Brodmann's area 9. Our results confirm that there are distinct aspects of inhibition and performance monitoring functions which come into play at various phases within a given trial of the SST, and that these are separable using fMRI.</AbstractText"
]
] |
[
[
"39810626",
"Recommendations for the Safe Application of Temporal Interference Stimulation in the Human Brain Part II: Biophysics, Dosimetry, and Safety Recommendations.",
"Temporal interference stimulation (TIS) is a new form of transcranial electrical stimulation (tES) that has been proposed as a method for targeted, noninvasive stimulation of deep brain structures. While TIS holds promise for a variety of clinical and nonclinical applications, little data is yet available regarding its effects in humans and its mechanisms of action. To inform the design and safe conduct of experiments involving TIS, researchers require quantitative guidance regarding safe exposure limits and other safety considerations. To this end, we undertook a two-part effort to determine frequency-dependent thresholds for applied currents below which TIS is unlikely to pose risk to humans in terms of heating or unwanted stimulation. In Part II of this effort, described here, we draw on a previously compiled list (see Part I) of adverse effects (AEs) reported for transcranial direct/alternating current stimulation (tDCS/ACS), deep brain stimulation (DBS), and TIS to determine biophysics-informed exposure metrics for assessing safety. Using an in silico approach, we conduct multiphysics simulations of various tACS, DBS, and TIS exposure scenarios in an anatomically detailed head and brain model. By matching the stimulation in terms of the identified exposure metrics, we infer frequency-dependent TIS parameters that produce exposure conditions equivalent to those known to be safe for tACS and DBS. Based on the results of our simulations and existing knowledge regarding tES and DBS safety, we propose frequency-dependent thresholds below which TIS voltages and currents are unlikely to pose a risk to humans. Safety-related data from ongoing and future human studies are required to verify and refine the thresholds proposed here.</AbstractText"
]
] |
38152804
|
Evaluation of 'Normal' Cognitive Functions and Correlation With MRI Volumetry: Towards a Definition of Vascular Cognitive Impairment.
|
Introduction It is important to establish criteria to define vascular cognitive impairment (VCI) in India as VCI is an image-based diagnosis and magnetic resonance imaging (MRI) changes resulting from age with prevalent vascular risk factors may confound MRI interpretation. The objective of this study was to establish normative community data for MRI volumetry including white matter hyperintensity volume (WMHV), correlated with age-stratified cognitive scores and vascular risk factors (VRFs), in adults aged 40 years and above.  Methods We screened 2651 individuals without known neurological morbidity, living in Mumbai and nearby rural areas, using validated Marathi translations of Kolkata Cognitive Battery (KCB) and geriatric depression score (GDS). We stratified 1961 persons with GDS ≤9 by age and cognitive score, and randomly selected 10% from each subgroup for MRI brain volumetry. Crude volumes were standardized to reflect percentage of intracranial volume.  Results MRI volumetry studies were done in 199 individuals (F/M = 90/109; 73 with body mass index (BMI) ≥25; 44 hypertensives; 29 diabetics; mean cognitive score 76.3). Both grey and white matter volumes decreased with increasing age. WMHV increased with age and hypertension. Grey matter volume (GMV) decreased with increasing WMHV. Positive predictors of cognition included standardized hippocampal volume (HCV), urban living, education, and BMI, while WMHV and age were negative predictors. Urban dwellers had higher cognitive scores than rural, and, paradoxically, smaller HCV.  Conclusion In this study of MRI volumetry correlated with age, cognitive scores and VRFs, increasing age and WMHV predicted lower cognitive scores, whereas urban living and hippocampal volume predicted higher scores. Age and WMHV also correlated with decreasing GMV. Further study is warranted into sociodemographic and biological factors that mutually influence cognition and brain volumes, including nutritional and endocrine factors, especially at lower cognitive score bands. In this study, at the lower KCB score bins, the lack of laboratory data pertaining to nutritional and endocrine deficiencies is a drawback that reflects the logistical limitations of screening large populations at the community level. Our volumetric data which is age and cognition stratified, and takes into account the vascular risk factors associated, nevertheless constitutes important baseline data for the Indian population. Our findings could possibly contribute to the formulation of baseline criteria for defining VCI in India and could help in early diagnosis and control of cognitive decline and its key risk factors.</AbstractText
|
[
[
"30962628",
"Working memory revived in older adults by synchronizing rhythmic brain circuits.",
"Understanding normal brain aging and developing methods to maintain or improve cognition in older adults are major goals of fundamental and translational neuroscience. Here we show a core feature of cognitive decline-working-memory deficits-emerges from disconnected local and long-range circuits instantiated by theta-gamma phase-amplitude coupling in temporal cortex and theta phase synchronization across frontotemporal cortex. We developed a noninvasive stimulation procedure for modulating long-range theta interactions in adults aged 60-76 years. After 25 min of stimulation, frequency-tuned to individual brain network dynamics, we observed a preferential increase in neural synchronization patterns and the return of sender-receiver relationships of information flow within and between frontotemporal regions. The end result was rapid improvement in working-memory performance that outlasted a 50 min post-stimulation period. The results provide insight into the physiological foundations of age-related cognitive impairment and contribute to groundwork for future non-pharmacological interventions targeting aspects of cognitive decline.</AbstractText"
]
] |
[
[
"36748121",
"Detecting and treating the protean manifestations of diabetic autonomic neuropathy.",
"The manifestations of diabetic autonomic neuropathy (DAN) are protean and clinically involve multiple systems, including the cardiovascular system, the gastrointestinal system, the genitourinary system as well as the sweat glands (sudomotor dysfunction) and the gallbladder. In addition, cardiac autonomic neuropathy (CAN) is associated with a correctible inability to appreciate and correct hypoglycaemia. While not a clinical problem, pupillary involvement should be the clue and the catalyst to investigate for other manifestations of DAN. This review outlines a practical approach to detecting and investigating the manifestations of DAN. Of particular importance is early detection of cardiovascular involvement where prompt therapy through glycaemic control can decrease the severity of CAN and decelerate the frequency and severity of retinopathy and nephropathy in addition to decreasing cardiovascular events and mortality. CAN also plays a role in accelerating other diabetic complications such as acute ischaemic stroke, heart failure, medial artery calcinosis, foot ulcers, peripheral artery disease and Charcot joints. Many therapies of DAN are available, which should not only decrease morbidity and mortality from DAN, but also improve the patient's quality of life. However, the therapies available are largely symptomatic.</AbstractText"
]
] |
40776133
|
Stroke Cohort Construction Using an Automated Clinical Data Collection System: An Experience of a Single Cerebrovascular Specialty Hospital in South Korea.
|
The growing volume of clinical data necessitates efficient management of Electronic Health Records (EHR) data. Traditional labor-intensive EHR management methods have led to significant risks, including high error rates and data omissions. This study modified and developed EHR templates focusing on key cohort-specific variables and developed a C#-based automated system for extracting and managing data from patients with acute stroke. The system reduced data entry time per patient from 35 minutes to 19 seconds. The data error rate decreased from 2.32% to 0.15%. This system enhances data management efficiency and is expected to support the construction of various cohorts through further expansion.</AbstractText
|
[
[
"24345399",
"Worldwide epidemiology of atrial fibrillation: a Global Burden of Disease 2010 Study.",
"The global burden of atrial fibrillation (AF) is unknown.</AbstractText We systematically reviewed population-based studies of AF published from 1980 to 2010 from the 21 Global Burden of Disease regions to estimate global/regional prevalence, incidence, and morbidity and mortality related to AF (DisModMR software). Of 377 potential studies identified, 184 met prespecified eligibility criteria. The estimated number of individuals with AF globally in 2010 was 33.5 million (20.9 million men [95% uncertainty interval (UI), 19.5-22.2 million] and 12.6 million women [95% UI, 12.0-13.7 million]). Burden associated with AF, measured as disability-adjusted life-years, increased by 18.8% (95% UI, 15.8-19.3) in men and 18.9% (95% UI, 15.8-23.5) in women from 1990 to 2010. In 1990, the estimated age-adjusted prevalence rates of AF (per 100 000 population) were 569.5 in men (95% UI, 532.8-612.7) and 359.9 in women (95% UI, 334.7-392.6); the estimated age-adjusted incidence rates were 60.7 per 100 000 person-years in men (95% UI, 49.2-78.5) and 43.8 in women (95% UI, 35.9-55.0). In 2010, the prevalence rates increased to 596.2 (95% UI, 558.4-636.7) in men and 373.1 (95% UI, 347.9-402.2) in women; the incidence rates increased to 77.5 (95% UI, 65.2-95.4) in men and 59.5 (95% UI, 49.9-74.9) in women. Mortality associated with AF was higher in women and increased by 2-fold (95% UI, 2.0-2.2) and 1.9-fold (95% UI, 1.8-2.0) in men and women, respectively, from 1990 to 2010. There was evidence of significant regional heterogeneity in AF estimations and availability of population-based data.</AbstractText These findings provide evidence of progressive increases in overall burden, incidence, prevalence, and AF-associated mortality between 1990 and 2010, with significant public health implications. Systematic, regional surveillance of AF is required to better direct prevention and treatment strategies.</AbstractText"
]
] |
[
[
"39481376",
"Combinatorial transcription factor binding encodes cis-regulatory wiring of mouse forebrain GABAergic neurogenesis.",
"Transcription factors (TFs) bind combinatorially to cis-regulatory elements, orchestrating transcriptional programs. Although studies of chromatin state and chromosomal interactions have demonstrated dynamic neurodevelopmental cis-regulatory landscapes, parallel understanding of TF interactions lags. To elucidate combinatorial TF binding driving mouse basal ganglia development, we integrated chromatin immunoprecipitation sequencing (ChIP-seq) for twelve TFs, H3K4me3-associated enhancer-promoter interactions, chromatin and gene expression data, and functional enhancer assays. We identified sets of putative regulatory elements with shared TF binding (TF-pRE modules) that orchestrate distinct processes of GABAergic neurogenesis and suppress other cell fates. The majority of pREs were bound by one or two TFs; however, a small proportion were extensively bound. These sequences had exceptional evolutionary conservation and motif density, complex chromosomal interactions, and activity as in vivo enhancers. Our results provide insights into the combinatorial TF-pRE interactions that activate and repress expression programs during telencephalon neurogenesis and demonstrate the value of TF binding toward modeling developmental transcriptional wiring.</AbstractText"
]
] |
40783178
|
Live-attenuated Toxoplasma gondii PruΔpp2a-c mutant elicits protective immunity against toxoplasmosis in mice and cats.
|
Toxoplasma gondii is a zoonotic protozoan pathogen capable of infecting humans and nearly all warm-blooded animals, and causing substantial economic losses to the livestock industry. Developing an effective vaccine against T. gondii remains an urgent priority for controlling the spread of this zoonotic parasite. In this study, we evaluated the protective efficacy of a live-attenuated T. gondii PruΔpp2a-c mutant in both mice and cats. Immunization with PruΔpp2a-c elicited strong cellular (IL-2, IL-4, IL-10, IL-12, and IFN-γ) and humoral (IgG, IgG1, and IgG2a) immune responses in mice, conferring protection against lethal challenge with various T. gondii strains, including highly virulent Type I (RH), mildly virulent ToxoDB#9 (PYS), and less virulent Type II (Pru) strains. While partial protection was observed against virulent strains, almost complete immune protection was achieved against both acute and chronic infections by the less virulent Pru strain, along with a significant reduction in brain cyst burden (P < 0.01). Notably, vaccination of cats with PruΔpp2a-c induced high antibody titers and led to a 94.5% reduction in fecal oocyst shedding (P < 0.001) following homologous challenge, thereby significantly decreasing the potential for environmental transmission. These findings demonstrate that PruΔpp2a-c provides strong cross-protection against various T. gondii strains and substantially limits oocyst shedding. The dual efficacy observed in both intermediate and definitive hosts highlights PruΔpp2a-c as a promising live-attenuated vaccine candidate for preventing transmission of T. gondii by cats.</AbstractText
|
[
[
"27432990",
"Dynamic neural activity during stress signals resilient coping.",
"Active coping underlies a healthy stress response, but neural processes supporting such resilient coping are not well-known. Using a brief, sustained exposure paradigm contrasting highly stressful, threatening, and violent stimuli versus nonaversive neutral visual stimuli in a functional magnetic resonance imaging (fMRI) study, we show significant subjective, physiologic, and endocrine increases and temporally related dynamically distinct patterns of neural activation in brain circuits underlying the stress response. First, stress-specific sustained increases in the amygdala, striatum, hypothalamus, midbrain, right insula, and right dorsolateral prefrontal cortex (DLPFC) regions supported the stress processing and reactivity circuit. Second, dynamic neural activation during stress versus neutral runs, showing early increases followed by later reduced activation in the ventrolateral prefrontal cortex (VLPFC), dorsal anterior cingulate cortex (dACC), left DLPFC, hippocampus, and left insula, suggested a stress adaptation response network. Finally, dynamic stress-specific mobilization of the ventromedial prefrontal cortex (VmPFC), marked by initial hypoactivity followed by increased VmPFC activation, pointed to the VmPFC as a key locus of the emotional and behavioral control network. Consistent with this finding, greater neural flexibility signals in the VmPFC during stress correlated with active coping ratings whereas lower dynamic activity in the VmPFC also predicted a higher level of maladaptive coping behaviors in real life, including binge alcohol intake, emotional eating, and frequency of arguments and fights. These findings demonstrate acute functional neuroplasticity during stress, with distinct and separable brain networks that underlie critical components of the stress response, and a specific role for VmPFC neuroflexibility in stress-resilient coping.</AbstractText"
]
] |
[
[
"40037512",
"A novel ferroptosis inhibitor phenothiazine derivative reduces cell death and alleviates neurological impairments after cerebral hemorrhage.",
"The precise etiology of brain injury induced by intracerebral hemorrhage (ICH) remains unclear. Currently, there are no effective therapeutic options available to slow down or prevent the progression of the disease. An increasing body of evidence suggests that ferroptosis plays a significant role in the development of injury related to ICH. Furthermore, pharmacological inhibition of ferroptosis has been identified as a promising therapeutic target for ICH injury. The compound 2-(1-(4-(4-methylpiperazin-1-yl)phenyl)ethyl)-10H-phenothiazine (compound-51), a derivative of promethazine, has been demonstrated to exhibit anti-ferroptosis and antioxidant properties. The aim of this study is to investigate the role and mechanism of action of compound-51 in a rat model of ICH. The in vivo experiments demonstrated that compound-51 significantly alleviated neurological impairments, reduced brain edema, and decreased hematoma volume. At the cellular level, compound-51 was observed to significantly enhance cellular survival and inhibit ferroptosis. Furthermore, compound-51 demonstrated a more pronounced therapeutic effect than Fer-1, without causing any injury to the heart, kidney, or liver. In vitro experiments demonstrated that compound-51 significantly increased cell viability and intracellular GPX4 levels, while reducing lipid peroxidation and oxidized glutathione levels. Collectively, these findings indicate that compound-51 exhibits a pronounced anti-ferroptosis function and alleviates neurological impairments in an ICH model, suggesting its potential as a new therapeutic agent for the treatment of ICH.</AbstractText"
]
] |
38195249
|
Treatment outcomes for ARUBA-eligible brain arteriovenous malformations: a comparison of real-world data from the NVQI-QOD AVM registry with the ARUBA trial.
|
Significant controversy exists about the management of unruptured cerebral arteriovenous malformations (AVMs). Results from A Randomized Trial of Unruptured Brain Arteriovenous Malformations (ARUBA) suggested that intervention increases the risk of stroke/death compared with medical management. However, numerous study limitations raised concerns about the trial's generalizability.</AbstractText To assess the rate of stroke/death and functional outcomes in ARUBA-eligible patients from a multicenter database, the Neurovascular Quality Initiative-Quality Outcomes Database (NVQI-QOD).</AbstractText We performed a retrospective analysis of prospectively collected data of ARUBA-eligible patients who underwent intervention at 18 participating centers. The primary endpoint was stroke/death from any cause. Secondary endpoints included neurologic, systemic, radiographic, and functional outcomes.</AbstractText 173 ARUBA-eligible patients underwent intervention with median follow-up of 269 (25-722.5) days. Seventy-five patients received microsurgery±embolization, 37 received radiosurgery, and 61 received embolization. Baseline demographics, risk factors, and general AVM characteristics were similar between groups. A total of 15 (8.7%) patients experienced stroke/death with no significant difference in primary outcome between treatment modalities. Microsurgery±embolization was more likely to achieve AVM obliteration (P<0.001). Kaplan-Meier survival curves demonstrated no difference in overall death/stroke outcomes between the different treatment modalities' 5-year period (P=0.087). Additionally, when compared with the ARUBA interventional arm, our patients were significantly less likely to experience death/stroke (8.7% vs 30.7%; P<0.001) and functional impairment (mRS score ≥2 25.4% vs 46.2%; P<0.01).</AbstractText Our results suggest that intervention for unruptured brain AVMs at comprehensive stroke centers across the United States is safe.</AbstractText
|
[
[
"26156615",
"Management of a solitary pulmonary arteriovenous malformation by video-assisted thoracoscopic surgery and anatomic lingula resection: video and review.",
"Pulmonary arteriovenous malformations are abnormal communications between the pulmonary arterial and venous vasculature leading to a right-to-left blood shunt. Based on possible complications, including hypoxemia, hemorrhage, infection and paradoxical embolism, deactivation of the malformation from the circulation is the treatment option of choice, either by interventional embolization or by surgery. Embolization is less invasive and has widely replaced surgery, but bears the risk of revascularization, recanalization and downstream migration of the device with paradoxical embolism.</AbstractText We report on the case of a 76-year-old male patient suffering from a complex, plexiform pulmonary arteriovenous malformation in the lingula, which was treated by video-assisted thoracoscopic surgery and anatomic lingula resection. Patient's medical history, clinical examination and imaging studies did not reveal any evidence of hereditary hemorrhagic telangiectasia.</AbstractText Left-sided anterior three-port video-assisted thoracoscopic surgery (VATS) approach was used. Instead of only wedge resecting the very peripherally located pulmonary arteriovenous malformation, the lingular vessels were controlled centrally and an anatomic lingula resection was performed in order to prevent a more central re-malformation. To prevent rupture of the aneurysm sac through pressure overload, the feeding arteries were controlled before the draining vein. Duration of the total procedure was 151 min, the single chest tube was removed on the postoperative day 3, and the patient was discharged on the postoperative day 6.</AbstractText Although interventional embolism of the feeding artery of a pulmonary arteriovenous malformation is the current therapeutic gold standard, minimally invasive anatomic lung resection by video-assisted thoracoscopic surgery can be considered, especially for the treatment of solitary large arteriovenous malformations. By anatomic lung resection, the risk of recanalization, collateralization and peri-interventional paradoxical embolism may be reduced.</AbstractText"
]
] |
[
[
"39595016",
"The Impact of Virtual Reality as a Rehabilitation Method Using TRAVEE System on Functional Outcomes and Disability in Stroke Patients: A Pilot Study.",
"Stroke is the third leading cause of disability. Virtual reality (VR) has shown promising results in post-stroke rehabilitation. The VR TRAVEE system was designed for the neuromotor rehabilitation of the upper limb after a stroke and offers the ability to track limb movements by providing auditory feedback and visual augmentation. The World Health Organization Disability Assessment Schedule 2.0 (WHODAS 2.0), aligned with the International Classification of Functioning, Disability, and Health (ICF) principles, is a valid tool for measuring disability regardless of its cause. This study aimed to investigate the feasibility of the VR TRAVEE system in upper limb rehabilitation for stroke patients.</AbstractText A total of 14 stroke patients with residual hemiparesis were enrolled in the study. They underwent a 10-day program combining conventional therapy (CnvT) with VR rehabilitation. At baseline (T0), the upper limb was assessed using the Modified Ashworth Scale (MAS), active range of motion (AROM), and the Numeric Rating Scale (NRS) for pain. These assessments were repeated after the 10-day rehabilitation program (T1). Additionally, disability was measured using WHODAS 2.0 at T0 and again 30 days after completing the program.</AbstractText Significant improvements were observed in AROM and MAS scores for the shoulder, elbow, wrist, and metacarpophalangeal joints, as well as in the reduction in shoulder pain (<i Combining CnvT with VR as a rehabilitation approach enhances motor function in the upper limb. This method has the potential to reduce disability scores and promote neuroplasticity.</AbstractText"
]
] |
40371132
|
Neural mechanisms of CALM intervention to improve CRCI in breast cancer survivors: an fMRI-based study.
|
Managing Cancer and Living Meaningfully (CALM) intervention's impact on chemotherapy-related cognitive impairment (CRCI) in breast cancer survivors (BCs) was investigated through resting-state functional magnetic resonance imaging (rs-fMRI) to elucidate the underlying neural mechanisms involved.</AbstractText 68 BCs were randomly assigned to either the CALM group (33 patients) or the care-as-usual (CAU) group (35 patients). Cognitive function was assessed before and after the intervention in both groups using the Mini Mental State Examination (MMSE) scale. Pre- and post-intervention rs-fMRI data were also collected for regional homogeneity (ReHo) and functional connectivity (FC) analyses in the CALM group. A total of 68 BCs were randomly assigned to either the CALM group (n = 33) or the care-as-usual (CAU) group (n = 35). Cognitive function was evaluated pre- and post-intervention using the Mini-Mental State Examination (MMSE). In the CALM group, rs-fMRI data were acquired before and after the intervention to assess alterations in regional homogeneity (ReHo) and functional connectivity (FC).</AbstractText CALM intervention demonstrated a greater enhancement in cognitive function compared to CAU (<i CALM intervention mitigates CRCI in BCs, with the middle frontal gyrus may play a critical.</AbstractText
|
[
[
"33308061",
"Why do imagery and perception look and feel so different?",
"Despite the past few decades of research providing convincing evidence of the similarities in function and neural mechanisms between imagery and perception, for most of us, the experience of the two are undeniably different, why? Here, we review and discuss the differences between imagery and perception and the possible underlying causes of these differences, from function to neural mechanisms. Specifically, we discuss the directional flow of information (top-down versus bottom-up), the differences in targeted cortical layers in primary visual cortex and possible different neural mechanisms of modulation versus excitation. For the first time in history, neuroscience is beginning to shed light on this long-held mystery of why imagery and perception look and feel so different. This article is part of the theme issue 'Offline perception: voluntary and spontaneous perceptual experiences without matching external stimulation'.</AbstractText"
]
] |
[
[
"39707024",
"Mechanical signaling through membrane tension induces somal translocation during neuronal migration.",
"Neurons migrate in a saltatory manner by repeating two distinct steps: extension of the leading process and translocation of the cell body. The former step is critical for determining the migratory route in response to extracellular guidance cues. In the latter step, neurons must generate robust forces that translocate the bulky soma against mechanical barriers of the surrounding three-dimensional environment. However, the link between the leading process extension and subsequent somal translocation remains unknown. By using the membrane tension sensor Flipper-TR and scanning ion conductance microscopy, we show that leading process extension increases plasma membrane tension. The tension elevation activated the mechanosensitive ion channel Tmem63b and triggered Ca<sup"
]
] |
37160674
|
Antitrust as a Guardrail for Socially Responsible Neurotechnology Design.
|
The neurotechnology sector is likely to develop under pressure towards commercialized, nonmedical products and may also undergo market consolidation. This possibility raises ethical, social, and policy concerns about the future responsibility of neurotechnology innovators and companies for high-consequence design decisions. Present-day internet technology firms furnish an instructive example of the problems that arise when providers of communicative technologies become too big for accountability. As a guardrail against the emergence of similar problems, concerned neurotechnologists may wish to draw inspiration from antitrust law and direct efforts, where appropriate, against undue consolidation in the commercial neurotechnology market.</AbstractText
|
[
[
"24904404",
"Decoding spectrotemporal features of overt and covert speech from the human cortex.",
"Auditory perception and auditory imagery have been shown to activate overlapping brain regions. We hypothesized that these phenomena also share a common underlying neural representation. To assess this, we used electrocorticography intracranial recordings from epileptic patients performing an out loud or a silent reading task. In these tasks, short stories scrolled across a video screen in two conditions: subjects read the same stories both aloud (overt) and silently (covert). In a control condition the subject remained in a resting state. We first built a high gamma (70-150 Hz) neural decoding model to reconstruct spectrotemporal auditory features of self-generated overt speech. We then evaluated whether this same model could reconstruct auditory speech features in the covert speech condition. Two speech models were tested: a spectrogram and a modulation-based feature space. For the overt condition, reconstruction accuracy was evaluated as the correlation between original and predicted speech features, and was significant in each subject (p < 10(-5); paired two-sample t-test). For the covert speech condition, dynamic time warping was first used to realign the covert speech reconstruction with the corresponding original speech from the overt condition. Reconstruction accuracy was then evaluated as the correlation between original and reconstructed speech features. Covert reconstruction accuracy was compared to the accuracy obtained from reconstructions in the baseline control condition. Reconstruction accuracy for the covert condition was significantly better than for the control condition (p < 0.005; paired two-sample t-test). The superior temporal gyrus, pre- and post-central gyrus provided the highest reconstruction information. The relationship between overt and covert speech reconstruction depended on anatomy. These results provide evidence that auditory representations of covert speech can be reconstructed from models that are built from an overt speech data set, supporting a partially shared neural substrate.</AbstractText"
]
] |
[
[
"36889873",
"Predicting Malignant Ventricular Arrhythmias Using Real-Time Remote Monitoring.",
"Although implantable cardioverter-defibrillator (ICD) therapies are associated with increased morbidity and mortality, the prediction of malignant ventricular arrhythmias has remained elusive.</AbstractText The purpose of this study was to evaluate whether daily remote-monitoring data may predict appropriate ICD therapies for ventricular tachycardia or ventricular fibrillation.</AbstractText This was a post hoc analysis of IMPACT (Randomized trial of atrial arrhythmia monitoring to guide anticoagulation in patients with implanted defibrillator and cardiac resynchronization devices), a multicenter, randomized, controlled trial of 2,718 patients evaluating atrial tachyarrhythmias and anticoagulation for patients with heart failure and ICD or cardiac resynchronization therapy with defibrillator devices. All device therapies were adjudicated as either appropriate (to treat ventricular tachycardia or ventricular fibrillation) or inappropriate (all others). Remote monitoring data in the 30 days before device therapy were utilized to develop separate multivariable logistic regression and neural network models to predict appropriate device therapies.</AbstractText A total of 59,807 device transmissions were available for 2,413 patients (age 64 ± 11 years, 26% women, 64% ICD). Appropriate device therapies (141 shocks, 10 antitachycardia pacing) were delivered to 151 patients. Logistic regression identified shock lead impedance and ventricular ectopy as significantly associated with increased risk of appropriate device therapy (sensitivity 39%, specificity 91%, AUC: 0.72). Neural network modeling yielded significantly better (P < 0.01 for comparison) predictive performance (sensitivity 54%, specificity 96%, AUC: 0.90), and also identified patterns of change in atrial lead impedance, mean heart rate, and patient activity as predictors of appropriate therapies.</AbstractText Daily remote monitoring data may be utilized to predict malignant ventricular arrhythmias in the 30 days before device therapies. Neural networks complement and enhance conventional approaches to risk stratification.</AbstractText"
]
] |
37756592
|
Attention-based generative adversarial networks improve prognostic outcome prediction of cancer from multimodal data.
|
The prediction of prognostic outcome is critical for the development of efficient cancer therapeutics and potential personalized medicine. However, due to the heterogeneity and diversity of multimodal data of cancer, data integration and feature selection remain a challenge for prognostic outcome prediction. We proposed a deep learning method with generative adversarial network based on sequential channel-spatial attention modules (CSAM-GAN), a multimodal data integration and feature selection approach, for accomplishing prognostic stratification tasks in cancer. Sequential channel-spatial attention modules equipped with an encoder-decoder are applied for the input features of multimodal data to accurately refine selected features. A discriminator network was proposed to make the generator and discriminator learning in an adversarial way to accurately describe the complex heterogeneous information of multiple modal data. We conducted extensive experiments with various feature selection and classification methods and confirmed that the CSAM-GAN via the multilayer deep neural network (DNN) classifier outperformed these baseline methods on two different multimodal data sets with miRNA expression, mRNA expression and histopathological image data: lower-grade glioma and kidney renal clear cell carcinoma. The CSAM-GAN via the multilayer DNN classifier bridges the gap between heterogenous multimodal data and prognostic outcome prediction.</AbstractText
|
[
[
"32300047",
"Categorical Signaling of the Strongest Stimulus by an Inhibitory Midbrain Nucleus.",
"The nucleus isthmi pars magnocellularis (Imc), a group of inhibitory neurons in the midbrain tegmentum, is a critical component of the spatial selection network in the vertebrate midbrain. It delivers long-range inhibition among different portions of the space map in the optic tectum (OT), thereby mediating stimulus competition in the OT. Here, we investigate the properties of relative strength-dependent competitive interactions within the Imc, in barn owls of both sexes. We find that when Imc neurons are presented simultaneously with one stimulus inside the receptive field and a second, competing stimulus outside, they exhibit gradual or switch-like response profiles as a function of relative stimulus strength. They do so both when the two stimuli are of the same sensory modality (both visual) or of different sensory modalities (visual and auditory). Moreover, Imc neurons signal the strongest stimulus in a dynamically flexible manner, indicating that Imc responses reflect an online comparison between the strengths of the competing stimuli. Notably, Imc neurons signal the strongest stimulus more categorically, and earlier than the OT. Paired recordings at spatially aligned sites in the Imc and OT reveal that although some properties of stimulus competition, such as the bias of competitive response profiles, are correlated, others such as the steepness of response profiles, are set independently. Our results demonstrate that the Imc is itself an active site of competition, and may be the first site in the midbrain selection network at which stimulus competition is resolved.<b"
]
] |
[
[
"37043357",
"Connexin 43-mediated neurovascular interactions regulate neurogenesis in the adult brain subventricular zone.",
"The subventricular zone (SVZ) is the largest neural stem cell (NSC) niche in the adult brain; herein, the blood-brain barrier is leaky, allowing direct interactions between NSCs and endothelial cells (ECs). Mechanisms by which direct NSC-EC interactions in the adult SVZ control NSC behavior are unclear. We found that Cx43 is highly expressed by SVZ NSCs and ECs, and its deletion in either leads to increased NSC proliferation and neuroblast generation, suggesting that Cx43-mediated NSC-EC interactions maintain NSC quiescence. This is further supported by single-cell RNA sequencing and in vitro studies showing that ECs control NSC proliferation by regulating expression of genes associated with NSC quiescence and/or activation in a Cx43-dependent manner. Cx43 mediates these effects in a channel-independent manner involving its cytoplasmic tail and ERK activation. Such insights inform adult NSC regulation and maintenance aimed at stem cell therapies for neurodegenerative disorders.</AbstractText"
]
] |
39387957
|
Advanced imaging reveals enhanced malignancy in glioblastomas involving the subventricular zone: evidence of increased infiltrative growth and perfusion.
|
Glioblastoma's infiltrative growth and heterogeneity are influenced by neural, molecular, genetic, and immunological factors, with the precise origin of these tumors remaining elusive. Neurogenic zones might serve as the tumor stem cells' nest, with tumors in contact with these zones exhibiting worse outcomes and more aggressive growth patterns. This study aimed to determine if these characteristics are reflected in advanced imaging, specifically diffusion and perfusion data.</AbstractText In this monocentric retrospective study, 137 glioblastoma therapy-naive patients (IDH-wildtype, grade 4) with advanced preoperative MRI, including perfusion and diffusion imaging, were analyzed. Tumors and neurogenic zones were automatically segmented. Advanced imaging metrics, including cerebral blood volume (CBV) from perfusion imaging, tissue volume mask (TVM), and free water corrected fractional anisotropy (FA-FWE) from diffusion imaging, were extracted.</AbstractText SVZ infiltration positively correlated with CBV, indicating higher perfusion in tumors. Significant CBV differences were noted between high and low SVZ infiltration cases at specific percentiles. Negative correlation was observed with TVM and positive correlation with FA-FWE, suggesting more infiltrative tumor growth. Significant differences in TVM and FA-FWE values were found between high and low SVZ infiltration cases.</AbstractText Glioblastomas with SVZ infiltration exhibit distinct imaging characteristics, including higher perfusion and lower cell density per voxel, indicating a more infiltrative growth and higher vascularization. Stem cell-like characteristics in SVZ-infiltrating cells could explain the increased infiltration and aggressive behavior. Understanding these imaging and biological correlations could enhance the understanding of glioblastoma evolution.</AbstractText
|
[
[
"26798224",
"Pre-Operative Perfusion Skewness and Kurtosis Are Potential Predictors of Progression-Free Survival after Partial Resection of Newly Diagnosed Glioblastoma.",
"To determine whether pre-operative perfusion skewness and kurtosis derived from normalized cerebral blood volume (nCBV) histograms are associated with progression-free survival (PFS) of patients after partial resection of newly diagnosed glioblastoma.</AbstractText A total of 135 glioblastoma patients who had undergone partial resection of tumor (resection of < 50% of pre-operative tumor volume or surgical biopsy) confirmed with immediate postsurgical MRI and examined with both conventional MRI and dynamic susceptibility contrast (DSC) perfusion MRI before the surgery were retrospectively reviewed in this study. They had been followed up post-surgical chemoradiotherapy for tumor progression. Using histogram analyses of nCBV derived from pre-operative DSC perfusion MRI, patients were sub-classified into the following four groups: positive skewness and leptokurtosis (group 1); positive skewness and platykurtosis (group 2); negative skewness and leptokurtosis (group 3); negative skewness and platykurtosis (group 4). Kaplan-Meier analysis and multivariable Cox proportional hazards regression analysis were performed to determine whether clinical and imaging covariates were associated with PFS or overall survival (OS) of these patients.</AbstractText According to the Kaplan-Meier method, median PFS of group 1, 2, 3, and 4 was 62, 51, 39, and 41 weeks, respectively, with median OS of 82, 77, 77, and 72 weeks, respectively. In multivariable analyses with Cox proportional hazards regression, pre-operative skewness/kurtosis pattern (hazard ratio: 2.98 to 4.64; p < 0.001), Karnofsky performance scale score (hazard ratio: 1.04; p = 0.003), and post-operative tumor volume (hazard ratio: 1.04; p = 0.02) were independently associated with PFS but not with OS.</AbstractText Higher skewness and kurtosis of nCBV histogram before surgery were associated with longer PFS in patients with newly diagnosed glioblastoma after partial tumor resection.</AbstractText"
]
] |
[
[
"40726664",
"A retrospective observational study of clinical and electrophysiological types of Guillain-Barre syndrome from Delhi.",
"To understand the demographic characteristics (age, sex and comorbidities), distribution of electrodiagnostic subtypes, and severity and prognosis of Guillain-Barre syndrome (GBS) variants.</AbstractText This 5-year retrospective study was conducted between January 2018 and December 2023. The patients (<i The patient group showed male predominance with an increased incidence with age. Antecedent infections were observed in 52 (38%) patients. Motor weakness, areflexia, and cranial nerve involvement (VII,IX,X,XI) were the most common clinical manifestations. The electrodiagnostic profiling included 96 (70%) patients with acute demyelinating polyradiculoneuropathy (AIDP), 25 (18.24%) patients of axonal forms and 16 (11%) patients of Bickerstaff Brainstem Encephalitis, Miller Fisher syndrome and paraparetic variants. Albumin cytological dissociation was documented in 61 (70%) patients out of 86 patients, which was more marked in AIDP than in other variants. The severity of GBS, using the Hughes disability score, was higher in patients with underlying diabetes mellitus. Recurrent GBS was observed in three (2%) and mortality rate was 2.91%.</AbstractText Our study showed a higher incidence of demyelination than that of axonal variants. There was more variation in albumin cytological dissociation in demyelinating subtypes than in the other variants. GBS severity was significantly higher in the patients with diabetes mellitus.</AbstractText"
]
] |
39163384
|
Childhood family socioeconomic status is linked to adult brain electrophysiology.
|
A large body of research has linked childhood family socioeconomic status (SES) to neurodevelopment in childhood and adolescence. However, it remains unclear to what extent childhood family SES relates to brain functioning in adulthood. To address this gap, the present study investigated the associations between retrospective accounts of objective and subjective childhood family SES and two well-established electrophysiological indices of brain functioning in adulthood-the MMN and P3b event-related potentials (ERP) components, as neural correlates of automatic change detection and cognitive control respectively. Higher objective childhood family SES, as proxied by parent educational attainment in childhood, was associated with larger (more positive) P3b amplitudes in adulthood. In contrast, there was no association between childhood parent educational attainment and the magnitude of MMN. Adult reports of subjective family SES during childhood were not related to the magnitude of MMN or P3b. These findings suggest that the links between childhood parent educational attainment and brain functioning may extend into adulthood, especially for brain functions supporting cognitive control. These results also imply that, when using retrospective accounts of childhood family SES, objective and subjective reports likely proxy different childhood experiences that have distinct links with specific neurodevelopmental outcomes, and that some of these links may not persist into adulthood. Our findings lay the groundwork for future investigations on how and why childhood family SES relates to brain functioning in adulthood.</AbstractText
|
[
[
"15131523",
"The role of GABA in the pathophysiology and treatment of anxiety disorders.",
"Mechanisms underlying the pathological characteristics of the various anxiety disorders have yet to be fully elucidated. One of the most widely accepted mediators known to play a central role in the pathophysiology of anxiety disorders is the g-aminobutyric acid (GABA) system. Evidence supporting the role of a dysfunctional GABA system has resulted from clinical experience with the benzodiazepines, as well as subsequent determination of mechanism of action, genetic engineering, and neuroimaging studies of the GABA receptor. The concatenation of results suggests a relative deficiency in GABA neurotransmission, which can be augmented by agents acting on different components of the GABA system. Agents such as the benzodiazepines, neuroactive steroids, and barbiturates act as allosteric modulators of the GABAA receptor; b-carboline and the barbiturates function as direct GABA agonists. Valproate, gabapentin, pregabalin, and vigabatrin increase brain GABA levels or neurotransmission at least in part by targeting the metabolic pathways of GABA. Tiagabine selectively increases synaptic GABA availability by blocking the reuptake of GABA via transporter inhibition. Evidence exists, to a greater or lesser extent, that all of these agents possess anxiolytic properties, as would be expected by their mechanisms of action. This article reviews the findings implicating the GABA system in the pathophysiology of anxiety disorders and describes the potential role of agents that modulate GABA neurotransmission in the treatment of these disorders.</AbstractText"
]
] |
[
[
"38472551",
"Ocrelizumab use in multiple sclerosis: a real-world experience in a changing therapeutic scenario.",
"CD20-depleting therapies are a real milestone in the treatment of multiple sclerosis (MS). This study examined the ocrelizumab (OCR) use in patients with primary progressive (PP) and relapsing remitting (RR) MS, also evaluating the predictors of treatment response.</AbstractText Patients with MS treated with OCR between 2017 and 2022 were included, and OCR use trends examined. The patients' characteristics were assessed at baseline and after 24 months of OCR to assess the NEDA-3 status.</AbstractText This study included 421 patients: 33 (7.9%) with PP and 388 (92.1%) with RR MS. Among these, 67 (17.3%) were naïve, while switchers from first- and second-line disease-modifying therapies (DMTs) were 199 (51.3%) and 122 (31.4%), respectively. An increasing trend in OCR use was reported. For six patients treated with rituximab, OCR was chosen to improve tolerability; for 390 switcher patients, the choice was due to ineffectiveness; and for 25, as an exit strategy from natalizumab due to JC virus positivity. NEDA-3 status was calculated for subjects exposed to 24 months of OCR and was achieved by 163/192 (84.9%) RR patients and 9/16 (56%) PP patients, with younger age (p = 0.048) and annualized relapse rate in the year previous to OCR (p = 0.005) emerging as determinants. For the 25 patients who switched to OCR after natalizumab, no clinical or MRI activity after 12 months was reported.</AbstractText OCR has been confirmed to be a highly efficacious option for patients with PP and RR MS, even proving to be a valid exit strategy for natalizumab.</AbstractText"
]
] |
40011296
|
Pyrrolidine Dithiocarbamate Ameliorates Sepsis-Associated Encephalopathy by Inhibiting Autophagy and Inflammation in the Brain.
|
Sepsis-associated encephalopathy (SAE) is common and has poor clinical outcome. Sepsis increases autophagy in the brain. This study was designed to determine the role of autophagy on SAE including the brain structures related to learning and memory and the effects of pyrrolidine dithiocarbamate (PDTC), an anti-inflammatory agent, on autophagy and SAE. Six- to eight-week old CD-1 male mice were subjected to cecal ligation and puncture (CLP). Some mice received intracerebroventricular injection of the autophagy suppressor 3-methyladenine (3-MA) or intraperitoneal injection of PDTC immediately at the completion of the CLP. ELISA was used to measure interleukin (IL)-1β, IL-6, IL-10, and tumor necrosis factor α. Autophagy-related protein expression in the cerebral cortex and hippocampus was analyzed by Western blotting. The cognitive functions of mice were analyzed by Barnes maze and fear conditioning tests. CLP increased microtubuleassociated protein light chain 3 II (LC3II) and Beclin 1 and decreased p62 in the brain. CLP also increased proinflammatory cytokines and impaired learning and memory. These effects were inhibited by 3-MA and PDTC. Spine proliferation and maturation were impaired by CLP, which was attenuated by PDTC and 3MA. Abundant autophagic vacuoles were observed by transmission electron microscopy in CLP group. LC3II immunostaining was co-localized with that of ionized calcium-binding adapter molecule 1 and microtubule-associated protein-2. The co-staining was attenuated by 3-MA and PDTC. Our results suggest that sepsis increases autophagy in the microglia and neurons. Inhibiting autophagy improves SAE and brain structures related to learning and memory in mice. Autophagy and inflammation in the brain may regulate each other during sepsis.</AbstractText
|
[
[
"37331262",
"Treatment outcomes of Veteran men in a comprehensive dialectical behavior therapy program: Characterizing sex differences in symptom trajectories.",
"Dialectical Behavior Therapy (DBT) is one of the primary psychosocial treatments for reducing suicidal behaviors and improving psychosocial outcomes among patients with borderline personality disorder (BPD) and has been shown to reduce BPD symptoms when delivered in a Veteran Affairs medical center setting. Despite evidence of similar rates of BPD in both men and women, the vast majority of treatment outcome research in BPD has focused on women. We sought to characterize sex differences in symptom trajectories among Veterans participating in a comprehensive DBT program. We found that Veteran men and women who entered the DBT program were diagnostically and demographically similar. Participants exhibited reductions in BPD symptoms and improvements in emotion regulation over the course of treatment. Moreover, Veteran men reported BPD symptom reductions that were not statistically inferior to those of Veteran women and exhibited a sharper reduction in these symptoms. This research provides support for the use of DBT as a psychosocial treatment for Veteran men with BPD symptoms.</AbstractText"
]
] |
[
[
"40543407",
"Exploring gastrocnemius medialis behavior during gait in children with cerebral palsy across different gait patterns.",
"Children with spastic cerebral palsy show varied gait patterns and muscle morphological alterations. We explored gastrocnemius medialis behavior during gait in typically developing children and children with cerebral palsy across different gait patterns.</AbstractText Eighteen children with spasticity of the leg muscles (female: 8, age: 11.1 ± 3.3 y) with a diagnosis of cerebral palsy (n = 17) or hereditary spastic paraplegia (n = 1) and 16 typically developing children (female: 11, age: 11.2 ± 3.2 y) walked on an instrumented treadmill. Three distinct gait patterns were determined in children with cerebral palsy. Muscle-tendon unit, fascicle, belly, and tendon behavior were assessed with dynamic ultrasound imaging. Unpaired statistical non-parametric mapping (SnPM) t-tests and Mann-Whitney U tests assessed differences between children with cerebral palsy and typically developing children. One-way ANOVA SnPM tests and Kruskall-Wallis tests assessed differences across gait patterns.</AbstractText Tendon lengthening in the first half of stance was higher in children with cerebral palsy compared to typically developing children (Δ6.6 mm), yet total tendon lengthening in stance (Δ5.3 mm) and fascicle shortening during push-off were decreased (Δ6.2 mm). Children with cerebral palsy displaying a mildly affected kinematic gait pattern showed pathological muscle belly lengthening in stance (Δ5.7 mm), while children with equinus (Δ6.4 mm) or crouch gait (Δ6.0 mm) showed reduced tendon lengthening.</AbstractText Efficient gastrocnemius medialis behavior is compromised in children with spastic cerebral palsy. Children with mildly affected gait show the most deviation in muscular components involved in active force generation, while those with equinus and crouch gait also show deviations in tendinous components. Interventions aimed at improving gait should consider this aberrant behavior.</AbstractText"
]
] |
35065321
|
Selenium ameliorates mercuric chloride-induced brain damage through activating BDNF/TrKB/PI3K/AKT and inhibiting NF-κB signaling pathways.
|
Mercuric chloride (HgCl<sub
|
[
[
"3025747",
"A new mechanism for induced vitamin D deficiency in calcium deprivation.",
"Synthesis of vitamin D in the skin in response to ultraviolet light is the main determinant of vitamin D status in man and it is therefore surprising that rickets and osteomalacia, clinical signs of vitamin D deficiency, remain common in tropical and subtropical countries. Skin pigmentation can reduce vitamin D formation but this is a negligible limitation in people exposed to abundant ultraviolet light. Earlier studies in animals and man suggested that another environmental factor, the low calcium/high cereal diet typical of susceptible populations, might affect the efficiency of vitamin D utilization. We show here in rats that the rate of inactivation of vitamin D in the liver is increased by calcium deprivation. The effect is mediated by 1,25-dihydroxyvitamin D, produced in response to secondary hyperparathyroidism, which promotes hepatic conversion of vitamin D to polar inactivation products that are excreted in bile. This finding has widespread implications both for understanding the pathogenesis of endemic rickets and in that it provides a unifying mechanism for the development of vitamin D deficiency in many clinical disorders.</AbstractText"
]
] |
[
[
"36685218",
"Sources of residual autocorrelation in multiband task fMRI and strategies for effective mitigation.",
"Analysis of task fMRI studies is typically based on using ordinary least squares within a voxel- or vertex-wise linear regression framework known as the general linear model. This use produces estimates and standard errors of the regression coefficients representing amplitudes of task-induced activations. To produce valid statistical inferences, several key statistical assumptions must be met, including that of independent residuals. Since task fMRI residuals often exhibit temporal autocorrelation, it is common practice to perform \"prewhitening\" to mitigate that dependence. Prewhitening involves estimating the residual correlation structure and then applying a filter to induce residual temporal independence. While theoretically straightforward, a major challenge in prewhitening for fMRI data is accurately estimating the residual autocorrelation at each voxel or vertex of the brain. Assuming a global model for autocorrelation, which is the default in several standard fMRI software tools, may under- or over-whiten in certain areas and produce differential false positive control across the brain. The increasing popularity of multiband acquisitions with faster temporal resolution increases the challenge of effective prewhitening because more complex models are required to accurately capture the strength and structure of autocorrelation. These issues are becoming more critical now because of a trend toward subject-level analysis and inference. In group-average or group-difference analyses, the within-subject residual correlation structure is accounted for implicitly, so inadequate prewhitening is of little real consequence. For individual subject inference, however, accurate prewhitening is crucial to avoid inflated or spatially variable false positive rates.</AbstractText In this paper, we first thoroughly examine the patterns, sources and strength of residual autocorrelation in multiband task fMRI data. Second, we evaluate the ability of different autoregressive (AR) model-based prewhitening strategies to effectively mitigate autocorrelation and control false positives. We consider two main factors: the choice of AR model order and the level of spatial regularization of AR model coefficients, ranging from local smoothing to global averaging. We also consider determining the AR model order optimally at every vertex, but we do not observe an additional benefit of this over the use of higher-order AR models (e.g. (AR(6)). To overcome the computational challenge associated with spatially variable prewhitening, we developed a computationally efficient R implementation using parallelization and fast C++ backend code. This implementation is included in the open source R package BayesfMRI.</AbstractText We find that residual autocorrelation exhibits marked spatial variance across the cortex and is influenced by many factors including the task being performed, the specific acquisition protocol, mis-modeling of the hemodynamic response function, unmodeled noise due to subject head motion, and systematic individual differences. We also find that local regularization is much more effective than global averaging at mitigating autocorrelation. While increasing the AR model order is also helpful, it has a lesser effect than allowing AR coefficients to vary spatially. We find that prewhitening with an AR(6) model with local regularization is effective at reducing or even eliminating autocorrelation and controlling false positives.</AbstractText Our analysis revealed dramatic spatial differences in autocorrelation across the cortex. This spatial topology is unique to each session, being influenced by the task being performed, the acquisition technique, various modeling choices, and individual differences. If not accounted for, these differences will result in differential false positive control and power across the cortex and across subjects.</AbstractText"
]
] |
34324976
|
Improvement of sensitivity and specificity for laminar BOLD fMRI with double spin-echo EPI in humans at 7 T.
|
Mapping mesoscopic cortical functional units such as columns or laminae is increasingly pursued by ultra-high field (UHF) functional magnetic resonance imaging (fMRI). The most popular approach for high-resolution fMRI is currently gradient-echo (GE) blood oxygenation level-dependent (BOLD) fMRI. However, its spatial accuracy is reduced due to its sensitivity to draining vessels, including pial veins, whereas spin-echo (SE) BOLD signal is expected to have higher spatial accuracy, albeit with lower sensitivity than the GE-BOLD signal. Here, we introduce a new double spin-echo (dSE) echo-planar imaging (EPI) method to improve the sensitivity of SE-BOLD contrast by averaging two spin-echoes using three radiofrequency pulses. Human fMRI experiments were performed with slices perpendicular to the central sulcus between motor and sensory cortices at 7 T during fist-clenching with touching. First, we evaluated the feasibility of single-shot dSE-EPI for BOLD fMRI with 1.5 mm isotropic resolution and found that dSE-BOLD fMRI has higher signal-to-noise ratio (SNR), temporal SNR (tSNR), and higher functional sensitivity than conventional SE-BOLD fMRI. Second, to investigate the laminar specificity of dSE-BOLD fMRI, we implemented a multi-shot approach to achieve 0.8-mm isotropic resolution with sliding-window reconstruction. Unlike GE-BOLD fMRI, the cortical profile of dSE-BOLD fMRI peaked at ~ 1.0 mm from the surface of the primary motor and sensory cortices, demonstrating an improvement of laminar specificity in humans over GE-BOLD fMRI. The proposed multi-shot dSE-EPI method is viable for high spatial resolution UHF-fMRI studies in the pursuit of resolving mesoscopic functional units.</AbstractText
|
[
[
"32936488",
"Segmented K-space blipped-controlled aliasing in parallel imaging for high spatiotemporal resolution EPI.",
"A segmented k-space blipped-controlled aliasing in parallel imaging (skipped-CAIPI) sampling strategy for EPI is proposed, which allows for a flexible choice of EPI factor and phase encode bandwidth independent of the controlled aliasing in parallel imaging (CAIPI) sampling pattern.</AbstractText With previously proposed approaches, exactly two EPI trajectories were possible given a specific CAIPI pattern, either with slice gradient blips (blipped-CAIPI) or following a shot-selective CAIPI approach (higher resolution). Recently, interleaved multi-shot segmentation along shot-selective CAIPI trajectories has been applied for high-resolution anatomical imaging. For more flexibility and a broader range of applications, we propose segmentation along any blipped-CAIPI trajectory. Thus, all EPI factors and phase encode bandwidths available with traditional segmented EPI can be combined with controlled aliasing.</AbstractText Temporal SNR maps of moderate-to-high-resolution time series acquisitions at varying undersampling factors demonstrate beneficial sampling alternatives to blipped-CAIPI or shot-selective CAIPI. Rapid high-resolution scans furthermore demonstrate SNR-efficient and motion-robust structural imaging with almost arbitrary EPI factor and minimal noise penalty.</AbstractText Skipped-CAIPI sampling increases protocol flexibility for high spatiotemporal resolution EPI. In terms of SNR and efficiency, high-resolution functional or structural scans benefit vastly from a free choice of the CAIPI pattern. Even at moderate resolutions, the independence of sampling pattern, TE, and image matrix size is valuable for optimized functional protocol design. Although demonstrated with 3D-EPI, skipped-CAIPI is also applicable with simultaneous multislice EPI.</AbstractText"
]
] |
[
[
"23103517",
"Towards a neural circuit model of verbal humor processing: an fMRI study of the neural substrates of incongruity detection and resolution.",
"The present study builds on our previous study within the framework of Wyer and Collin's comprehension-elaboration theory of humor processing. In this study, an attempt is made to segregate the neural substrates of incongruity detection and incongruity resolution during the comprehension of verbal jokes. Although a number of fMRI studies have investigated the incongruity-resolution process, the differential neurological substrates of comprehension are still not fully understood. The present study utilized an event-related fMRI design incorporating three conditions (unfunny, nonsensical and funny) to examine distinct brain regions associated with the detection and resolution of incongruities. Stimuli in the unfunny condition contained no incongruities; stimuli in the nonsensical condition contained irresolvable incongruities; and stimuli in the funny condition contained resolvable incongruities. The results showed that the detection of incongruities was associated with greater activation in the right middle temporal gyrus and right medial frontal gyrus, and the resolution of incongruities with greater activation in the left superior frontal gyrus and left inferior parietal lobule. Further analysis based on participants' rating scores provided converging results. Our findings suggest a three-stage neural circuit model of verbal humor processing: incongruity detection and incongruity resolution during humor comprehension and inducement of the feeling of amusement during humor elaboration.</AbstractText"
]
] |
30605083
|
Adaptive Matching Transmitter With Dual-Band Antenna for Intraoral Tongue Drive System.
|
The intraoral Tongue Drive System (iTDS) is a wireless assistive technology that detects users' voluntary tongue gestures, and converts them to user-defined commands, enabling them to access computers and navigate powered wheelchairs. In this paper, we presented a transmitter (Tx) with adaptive matching and three bands (27, 433, and 915 MHz) to create a robust wireless link between iTDS and an external receiver (Rx) by addressing the effects of external RF interference and impedance variations of the Tx antenna in the dynamic mouth environment. The upper two Tx bands share a dual-band antenna, while the lower band drives a coil. The Tx antenna is simulated in a simplified human mouth model in HFSS as well as a real human head model. The adaptive triple-band Tx chip was fabricated in a 0.35-μm 4P2M standard CMOS process. The Tx chip and antenna have been characterized in a human subject as part of an iTDS prototype under open-and closed-mouth scenarios, which present the peak gain of -24.4 and -15.63 dBi at 433 and 915 MHz, respectively. Two adaptive matching networks for these bands compensate variations of the Tx antenna impedance via a feedback mechanism. The measured S<sub
|
[
[
"23556919",
"A prototype MR insertable brain PET using tileable GAPD arrays.",
"The aim of this study was to develop a prototype magnetic resonance (MR)-compatible positron emission tomography (PET) that can be inserted into a MR imager and that allows simultaneous PET and MR imaging of the human brain. This paper reports the initial results of the authors' prototype brain PET system operating within a 3-T magnetic resonance imaging (MRI) system using newly developed Geiger-mode avalanche photodiode (GAPD)-based PET detectors, long flexible flat cables, position decoder circuit with high multiplexing ratio, and digital signal processing with field programmable gate array-based analog to digital converter boards.</AbstractText A brain PET with 72 detector modules arranged in a ring was constructed and mounted in a 3-T MRI. Each PET module was composed of cerium-doped lutetium yttrium orthosilicate (LYSO) crystals coupled to a tileable GAPD. The GAPD output charge signals were transferred to preamplifiers using 3 m long flat cables. The LYSO and GAPD were located inside the MR bore and all electronics were positioned outside the MR bore. The PET detector performance was investigated both outside and inside the MRI, and MR image quality was evaluated with and without the PET system.</AbstractText The performance of the PET detector when operated inside the MRI during MR image acquisition showed no significant change in energy resolution and count rates, except for a slight degradation in timing resolution with an increase from 4.2 to 4.6 ns. Simultaneous PET/MR images of a hot-rod and Hoffman brain phantom were acquired in a 3-T MRI. Rods down to a diameter of 3.5 mm were resolved in the hot-rod PET image. The activity distribution patterns between the white and gray matter in the Hoffman brain phantom were well imaged. The hot-rod and Hoffman brain phantoms on the simultaneously acquired MR images obtained with standard sequences were observed without any noticeable artifacts, although MR image quality requires some improvement.</AbstractText These results demonstrate that the simultaneous acquisition of PET and MR images is feasible using the MR insertable PET developed in this study.</AbstractText"
]
] |
[
[
"29446125",
"Feasibility of high spatiotemporal resolution for an abbreviated 3D radial breast MRI protocol.",
"To develop a volumetric imaging technique with 0.8-mm isotropic resolution and 10-s/volume rate to detect and analyze breast lesions in a bilateral, dynamic, contrast-enhanced MRI exam.</AbstractText A local low-rank temporal reconstruction approach that also uses parallel imaging and spatial compressed sensing was designed to create rapid volumetric frame rates during a contrast-enhanced breast exam (vastly undersampled isotropic projection [VIPR] spatial compressed sensing with temporal local low-rank [STELLR]). The dynamic-enhanced data are subtracted in k-space from static mask data to increase sparsity for the local low-rank approach to maximize temporal resolution. A T<sub The STELLR temporal performance of subtracted data matched the expected temporal perfusion enhancement pattern in small and large vascular structures. Differential enhancement within heterogeneous lesions is demonstrated with corroboration from a basic reconstruction using a strict 10-second temporal footprint. Rapid acquisition, reliable fat suppression, and high spatiotemporal resolution are presented, despite significant data undersampling.</AbstractText The STELLR reconstruction approach of 3D radial sampling with mask subtraction provides a high-performance imaging technique for characterizing enhancing structures within the breast. It is capable of maintaining temporal fidelity, while visualizing breast lesions with high detail over a large FOV to include both breasts.</AbstractText"
]
] |
39730017
|
Forsythoside B ameliorates neuroinflammation via inhibiting NLRP3 inflammasome of glial cells in experimental autoimmune encephalomyelitis mice.
|
Neuroinflammation mediated by glial cells plays a crucial role in demyelination in experimental autoimmune encephalomyelitis (EAE), a multiple sclerosis (MS) model. Forsythoside B (FTS·B), a natural phenylethanoid glycoside isolated from the dried fruits and leaves of Forsythia suspensa (Thunb.) Vahl, has been found to have antioxidant, anti-apoptotic, and anti-inflammatory properties. However, there is currently no report or research on the effectiveness of FTS·B treatment for EAE. The aim of this study was to investigate the neuroprotective properties of (FTS·B) on EAE and reveal its potential mechanisms. Myelin oligodendrocyte glycoprotein-induced EAE mice were randomly categorized into the control, EAE model, and FTS·B treatment groups. Behavioral testing, pathology, immunohistochemistry, immunofluorescence staining, and western blot analysis of spinal cord tissue were used to determine the effects and mechanisms of FTS·B on EAE in mice. We found that FTS·B treatment could significantly alleviate and reduce the clinical symptoms and morbidity of EAE, respectively. In addition, FTS·B administration reduced inflammatory response and demyelination by inhibiting glial cell activation in the spinal cord of EAE mice. Further experiments confirmed that FTS·B inhibited the formation of NLRP3 inflammasome in microglia and astrocytes, thereby suppressing neuroinflammation and GSDMD-mediated pyroptosis. Altogether, these results suggest that FTS·B treatment attenuates central neuroinflammation and pyroptosis by inhibiting NLRP3 inflammasome of glial cells in EAE mice.</AbstractText
|
[
[
"31740269",
"Mitochondrial impairment activates the Wallerian pathway through depletion of NMNAT2 leading to SARM1-dependent axon degeneration.",
"Wallerian degeneration of physically injured axons involves a well-defined molecular pathway linking loss of axonal survival factor NMNAT2 to activation of pro-degenerative protein SARM1. Manipulating the pathway through these proteins led to the identification of non-axotomy insults causing axon degeneration by a Wallerian-like mechanism, including several involving mitochondrial impairment. Mitochondrial dysfunction is heavily implicated in Parkinson's disease, Charcot-Marie-Tooth disease, hereditary spastic paraplegia and other axonal disorders. However, whether and how mitochondrial impairment activates Wallerian degeneration has remained unclear. Here, we show that disruption of mitochondrial membrane potential leads to axonal NMNAT2 depletion in mouse sympathetic neurons, increasing the substrate-to-product ratio (NMN/NAD) of this NAD-synthesising enzyme, a metabolic fingerprint of Wallerian degeneration. The mechanism appears to involve both impaired NMNAT2 synthesis and reduced axonal transport. Expression of WLD<sup"
]
] |
[
[
"39934999",
"MacaqueNet: Advancing comparative behavioural research through large-scale collaboration.",
"There is a vast and ever-accumulating amount of behavioural data on individually recognised animals, an incredible resource to shed light on the ecological and evolutionary drivers of variation in animal behaviour. Yet, the full potential of such data lies in comparative research across taxa with distinct life histories and ecologies. Substantial challenges impede systematic comparisons, one of which is the lack of persistent, accessible and standardised databases. Big-team approaches to building standardised databases offer a solution to facilitating reliable cross-species comparisons. By sharing both data and expertise among researchers, these approaches ensure that valuable data, which might otherwise go unused, become easier to discover, repurpose and synthesise. Additionally, such large-scale collaborations promote a culture of sharing within the research community, incentivising researchers to contribute their data by ensuring their interests are considered through clear sharing guidelines. Active communication with the data contributors during the standardisation process also helps avoid misinterpretation of the data, ultimately improving the reliability of comparative databases. Here, we introduce MacaqueNet, a global collaboration of over 100 researchers (https://macaquenet.github.io/) aimed at unlocking the wealth of cross-species data for research on macaque social behaviour. The MacaqueNet database encompasses data from 1981 to the present on 61 populations across 14 species and is the first publicly searchable and standardised database on affiliative and agonistic animal social behaviour. We describe the establishment of MacaqueNet, from the steps we took to start a large-scale collective, to the creation of a cross-species collaborative database and the implementation of data entry and retrieval protocols. We share MacaqueNet's component resources: an R package for data standardisation, website code, the relational database structure, a glossary and data sharing terms of use. With all these components openly accessible, MacaqueNet can act as a fully replicable template for future endeavours establishing large-scale collaborative comparative databases.</AbstractText"
]
] |
16196033
|
Constitutive neuronal expression of CCR2 chemokine receptor and its colocalization with neurotransmitters in normal rat brain: functional effect of MCP-1/CCL2 on calcium mobilization in primary cultured neurons.
|
Chemokines and their receptors are well described in the immune system, where they promote cell migration and activation. In the central nervous system, chemokine has been implicated in neuroinflammatory processes. However, an increasing number of evidence suggests that they have regulatory functions in the normal nervous system, where they could participate in cell communication. In this work, using a semiquantitative immunohistochemistry approach, we provide the first neuroanatomical mapping of constitutive neuronal CCR2 localization. Neuronal expression of CCR2 was observed in the anterior olfactory nucleus, cerebral cortex, hippocampal formation, caudate putamen, globus pallidus, supraoptic and paraventricular hypothalamic nuclei, amygdala, substantia nigra, ventral tegmental area, and in the brainstem and cerebellum. These data are largely in accordance with results obtained using quantitative autoradiography with [(125)I]MCP-1/CCL2 and RT-PCR CCR2 mRNA analysis. Furthermore, using dual fluorescent immunohistochemistry we studied the chemical phenotype of labeled neurons and demonstrated the coexistence of CCR2 with classical neurotransmitters. Indeed, localization of CCR2 immunostaining is observed in dopaminergic neurons in the substantia nigra pars compacta and in the ventral tegmental area as well as in cholinergic neurons in the substantia innominata and caudate putamen. Finally, we show that the preferential CCR2 ligand, MCP-1/CCL2, elicits Ca(2+) transients in primary cultured neurons from various rat brain regions including the cortex, hippocampus, hypothalamus, and mesencephalon. In conclusion, the constitutive neuronal CCR2 expression in selective brain structures suggests that this receptor could be involved in neuronal communication and possibly associated with cholinergic and dopaminergic neurotransmission and related disorders.</AbstractText
|
[
[
"36857176",
"Positive and negative allosteric modulation of GluK2 kainate receptors by BPAM344 and antiepileptic perampanel.",
"Kainate receptors (KARs) are a subtype of ionotropic glutamate receptors that control synaptic transmission in the central nervous system and are implicated in neurological, psychiatric, and neurodevelopmental disorders. Understanding the regulation of KAR function by small molecules is essential for exploring these receptors as drug targets. Here, we present cryoelectron microscopy (cryo-EM) structures of KAR GluK2 in complex with the positive allosteric modulator BPAM344, competitive antagonist DNQX, and negative allosteric modulator, antiepileptic drug perampanel. Our structures show that two BPAM344 molecules bind per ligand-binding domain dimer interface. In the absence of an agonist or in the presence of DNQX, BPAM344 stabilizes GluK2 in the closed state. The closed state is also stabilized by perampanel, which binds to the ion channel extracellular collar sites located in two out of four GluK2 subunits. The molecular mechanisms of positive and negative allosteric modulation of KAR provide a guide for developing new therapeutic strategies.</AbstractText"
]
] |
[
[
"38010204",
"Associations between white matter integrity of the cingulum bundle, surrounding gray matter regions, and cognition across the dementia continuum.",
"Previous Alzheimer's disease and related dementias (AD/ADRD) research studies have illustrated the significance of studying alterations in white matter (WM). Fewer studies have examined how WM integrity, measured with diffusion tensor imaging (DTI), is associated with volume of gray matter (GM) regions and measures of cognitive function in aged participants spanning the dementia continuum.</AbstractText Magnetic resonance imaging and cognitive data were collected from 241 Boston University Alzheimer's Disease Research Center participants who spanned from cognitively normal controls to amnestic mild cognitive impairment to having dementia. Primary DTI tracts of interest were the cingulum ventral (CV) and cingulum dorsal (CD) pathways. GM regions of interest (ROIs) were in the medial temporal lobe (MTL), prefrontal cortex, and retrosplenial cortex. Analyses of covariance models were used to assess differences in WM integrity across groups (control, amnestic mild cognitive impairment, and dementia). Multiple linear regression models were used to assess associations between WM integrity and GM volume, and with measures of memory and executive function.</AbstractText Differences in WM integrity were shown in both cingulum pathways in participants across the dementia continuum. Associations between WM integrity of both cingulum pathways and volume of selected GM ROIs were widespread. Functionally significant associations were found between WM of the CV pathway and memory, independent of MTL GM volume.</AbstractText Differences in WM integrity of the cingulum bundle and surrounding GM ROI are likely related to the progression of AD/ADRD. Such differences should continue to be studied, particularly in association with memory performance.</AbstractText"
]
] |
34132175
|
Creutzfeldt-Jakob disease in pregnancy: the use of modified RT-QuIC to determine infectivity in placental tissues.
|
Sporadic Creutzfeldt-Jakob Disease (sCJD) rarely affects women of childbearing age. There is currently no evidence of vertical transmission. Given the biosafety implications of performing Caesarean sections (C-section) in these patients, we used sensitive real-time quaking-induced conversion (RT-QuIC) assays to test for the infectious prion protein (PrP<sup
|
[
[
"29186501",
"The Amygdala as a Locus of Pathologic Misfolding in Neurodegenerative Diseases.",
"Over the course of most common neurodegenerative diseases the amygdala accumulates pathologically misfolded proteins. Misfolding of 1 protein in aged brains often is accompanied by the misfolding of other proteins, suggesting synergistic mechanisms. The multiplicity of pathogenic processes in human amygdalae has potentially important implications for the pathogenesis of Alzheimer disease, Lewy body diseases, chronic traumatic encephalopathy, primary age-related tauopathy, and hippocampal sclerosis, and for the biomarkers used to diagnose those diseases. Converging data indicate that the amygdala may represent a preferential locus for a pivotal transition from a relatively benign clinical condition to a more aggressive disease wherein multiple protein species are misfolded. Thus, understanding of amygdalar pathobiology may yield insights relevant to diagnoses and therapies; it is, however, a complex and imperfectly defined brain region. Here, we review aspects of amygdalar anatomy, connectivity, vasculature, and pathologic involvement in neurodegenerative diseases with supporting data from the University of Kentucky Alzheimer's Disease Center autopsy cohort. Immunohistochemical staining of amygdalae for Aβ, Tau, α-synuclein, and TDP-43 highlight the often-coexisting pathologies. We suggest that the amygdala may represent an \"incubator\" for misfolded proteins and that it is possible that misfolded amygdalar protein species are yet to be discovered.</AbstractText"
]
] |
[
[
"33143627",
"Diabetes and Its Complications: Therapies Available, Anticipated and Aspired.",
"Worldwide, diabetes ranks among the ten leading causes of mortality. Prevalence of diabetes is growing rapidly in low and middle income countries. It is a progressive disease leading to serious co-morbidities, which results in increased cost of treatment and over-all health system of the country. Pathophysiological alterations in Type 2 Diabetes (T2D) progressed from a simple disturbance in the functioning of the pancreas to triumvirate to ominous octet to egregious eleven to dirty dozen model. Due to complex interplay of multiple hormones in T2D, there may be multifaceted approach in its management. The 'long-term secondary complications' in uncontrolled diabetes may affect almost every organ of the body, and finally may lead to multi-organ dysfunction. Available therapies are inconsistent in maintaining long term glycemic control and their long term use may be associated with adverse effects. There is need for newer drugs, not only for glycemic control but also for prevention or mitigation of secondary microvascular and macrovascular complications. Increased knowledge of the pathophysiology of diabetes has contributed to the development of novel treatments. Several new agents like Glucagon Like Peptide - 1 (GLP-1) agonists, Dipeptidyl Peptidase IV (DPP-4) inhibitors, amylin analogues, Sodium-Glucose transport -2 (SGLT- 2) inhibitors and dual Peroxisome Proliferator-Activated Receptor (PPAR) agonists are available or will be available soon, thus extending the range of therapy for T2D, thereby preventing its long term complications. The article discusses the pathophysiology of diabetes along with its comorbidities, with a focus on existing and novel upcoming antidiabetic drugs which are under investigation. It also dives deep to deliberate upon the novel therapies that are in various stages of development. Adding new options with new mechanisms of action to the treatment armamentarium of diabetes may eventually help improve outcomes and reduce its economic burden.</AbstractText"
]
] |
End of preview. Expand
in Data Studio
YAML Metadata
Warning:
empty or missing yaml metadata in repo card
(https://huggingface.co/docs/hub/datasets-cards)
Jerjes/neuro-specter2-triplets-pool
This dataset contains anchor papers with their top-K most similar (positive) and most dissimilar (negative) papers based on SPECTER2 embeddings.
Dataset Structure
Each row contains:
anchor_id: Unique identifier for the anchor paperanchor_title: Title of the anchor paperanchor_abstract: Abstract of the anchor paperpositive_pool: List of 5 most similar papers, each as [id, title, abstract]negative_pool: List of 5 most dissimilar papers, each as [id, title, abstract]
Dataset Statistics
- Total anchors: 250,000
- Positives per anchor: 5
- Negatives per anchor: 5
- Embedding model: allenai/specter2_base
Usage
from datasets import load_dataset
dataset = load_dataset("Jerjes/neuro-specter2-triplets-pool")
# Access a sample
sample = dataset["train"][0]
print(f"Anchor: {sample['anchor_title']}")
print(f"Top positive: {sample['positive_pool'][0][1]}") # title of most similar paper
print(f"Top negative: {sample['negative_pool'][0][1]}") # title of most dissimilar paper
Citation
If you use this dataset, please cite the original SPECTER2 paper:
@inproceedings{specter2,
title={SPECTER2: Better Scientific Paper Representations Through Augmented Word Embeddings},
author={Pradeep Dasigi and Kyle Lo and Iz Beltagy and Arman Cohan and Noah A. Smith and Matt Gardner},
booktitle={Proceedings of the 2021 Conference on Empirical Methods in Natural Language Processing},
year={2021}
}
- Downloads last month
- 3