Accumulation of tissue-resident natural killer cells, innate lymphoid cells, and CD8+ T cells towards the center of human lung tumors

Abstract: Lung cancer is a leading cause of cancer-related death worldwide. Despite recent advances in tissue immunology, little is known about the spatial distribution of tissue-resident lymphocyte subsets in lung tumors. Using high-parameter flow cytometry, we identified an accumulation of tissue-resident lymphocytes including tissue-resident NK (trNK) cells and CD8+ tissue-resident memory T (TRM) cells toward the center of human non-small cell lung carcinomas (NSCLC). Chemokine receptor expression patterns indicated different modes of tumor-infiltration and/or residency between trNK cells and CD8+ TRM cells. In contrast to CD8+ TRM cells, trNK cells and ILCs generally expressed low levels of immune checkpoint receptors independent of location in the tumor. Additionally, granzyme expression in trNK cells and CD8+ TRM cells was highest in the tumor center, and intratumoral CD49a+CD16− NK cells were functional and responded stronger to target cell stimulation than their CD49a− counterparts, indicating functional relevance of trNK cells in lung tumors.In summary, the present spatial mapping of lymphocyte subsets in human NSCLC provides novel insights into the composition and functionality of tissue-resident immune cells, suggesting a role for trNK cells and CD8+ TRM cells in lung tumors and their potential relevance for future therapeutic approaches.

Demi Brownlie
Andreas von Kries
Giampiero Valenzano
Nicole Wild
Emel Yilmaz
Jesper Säfholm
Mamdoh Al-Ameri
Evren Alici
Hans-Gustaf Ljunggren
Igor Schliemann
Ozan Aricak
Felix Haglund de Flon
Jakob Michaëlsson
Nicole Marquardt

Neoplasms. Tumors. Oncology. Including cancer and carcinogens


Correction

Business
Management. Industrial management


Platinum-free counter electrodes of plasma-modified hybrid nanomaterials for dye-sensitised solar cells

Abstract: Molybdenum disulphide (MoS2) nanotube and tungsten oxide (W18O49) nanowire were coated with poly(3-hexylthiophene) (P3HT) and poly(3,4-ethylenedioxythiophene) (PEDOT) by a radio frequency (RF: 13.56 MHz)-rotating plasma-modification method as alternative counter electrodes for dye-sensitised solar cells (DSSCs). Surface analysis showed the homogenous plasma nanocoating of inorganic nanostructures by P3HT and PEDOT. It was demonstrated that the plasma-modified hybrid platinum-free counter electrodes increased the efficiencies of the DSSCs. The DSSCs based on hybrid nanostructure materials showed a short circuit current density of 9.49, 7.95, 2.59 and 2.57 mAcm−2 for MoS2/P3HT, MoS2/PEDOT, W18O49/PEDOT and W18O49/P3HT samples, respectively. The plasma nanocoating with the nanostructured materials approach for obtaining hybrid counter electrodes in the photovoltaic action shows an alternative route towards cost-effective, green energy conversion.

Sule Erten-Ela
Melek Kiristi
Ana Varlec
Ferhat Bozduman
Maja Remskar
Lutfi Oksuz
Aysegul Uygun Oksuz

International Journal of Sustainable Energy


Psychological impacts of AI-induced job displacement among Indian IT professionals: a Delphi-validated thematic analysis

Abstract: Purpose This study investigates the psychological impact of Artificial Intelligence (AI)-driven job displacement among Indian IT professionals. It specifically explores how individuals psychologically experience the loss of roles due to automation, and how these experiences influence their emotional, cognitive, and behavioural well-being. Method A qualitative phenomenological approach was used to capture the lived experiences of 24 IT professionals who faced AI-induced job loss or reassignment. Data were collected via in-depth semi-structured interviews and analysed through thematic analysis. To ensure rigour and theoretical saturation, a three-round Delphi process involving 20 domain experts—spanning clinical psychology, organizational behaviour, and AI policy—was used to validate and refine the emergent themes. Results Six core psychological themes were identified: emotional shock, erosion of professional identity, chronic anxiety and anticipatory rumination, social withdrawal, adaptive and maladaptive coping strategies, and perceived organizational betrayal. These themes reflect a multilayered resource loss, including identity, control, employability, and social belonging. Conclusion AI-driven role redundancy in the Indian IT sector is more than a labour market shift a deep psychological disruption. This study underscores the urgent need for organizations, mental health practitioners, and policymakers to develop anticipatory and compassionate interventions that can buffer the mental health consequences of technological transformation.

Vinod Sharma
Saikat Deb
Yogesh Mahajan
Avishek Ghosal
Manohar Kapse

International Journal of Qualitative Studies on Health & Well-Being


Satellite-derived prediction on habitat modelling of skipjack tuna (Katsuwonus pelamis) in the Makassar Strait, Indonesia

Abstract: The Makassar Strait is one of the Indonesian Throughflow (ITF) branches that transports warm water masses from the Pacific Ocean to the Indian Ocean. These water masses have a significant impact on oceanographic parameters, which in turn affects the skipjack tuna distribution. Satellite-derived oceanographic factors from January 2015 to December 2020 included sea surface temperature (SST), chlorophyll-a, salinity, sea surface height (SSH), surface current, and surface wind are used to predict the potential habitat of skipjack tuna (Katsuwonus pelamis) in the Makassar Strait using the maximum entropy (MaxEnt) model. The SSH was the most important oceanographic variable affecting the skipjack tuna catch, contributing 49.7% to the model gain. An increasing skipjack tuna catch was observed within the following oceanographic variable ranges: 0.48–0.58 m of SSH, 34–35 ppt of salinity, 0.1–1.2 m/s of surface current, 29–30 °C of SST, 5–6 m/s of surface wind, and 0.1–0.5 mg/l of chlorophyll-a concentrations.

Mega L. Syamsuddin
Subiyanto Subiyanto
Tonny Bratasena
Fadli Syamsudin
Noir P. Purba
Yudi Nurul Ihsan
Ajeng R. Puspita
Mukti Zainuddin
Nofrita Nofrita


AI-enhanced professional learning communities: a new era of personalized teacher education

Abstract: Language teacher education programs can become more reflective, inclusive, collaborative, situated, and inquiry-based. One such professional approach to incorporate these characters can be through personalized language teacher education (PLTE). Due to the importance of using AI and professional learning communities (PLCs) for developing a personalized teacher education, this study explored how AI-enhanced PLCs could be leveraged to create a more responsive, inclusive, and personalized teacher education. Still, a significant gap exists in understanding how AI can be specially integrated into PLCs to create personalized pathways for ELT preservice teachers, mainly in under-resourced contexts. To conduct this exploratory case study, 8 Iranian English language teaching (ELT) pre-service teachers were purposively selected from a teacher education university. Data was collected from group discussion, artifacts, and interviews, and the result of the thematic analysis revealed that AI-enhanced PLCs fostered personalized, reflective, and collaborative development by addressing individual teaching needs and providing innovative strategies. By addressing individual teaching needs and providing innovative instructional strategies, AI facilitated a dynamic learning environment. However, effective integration required overcoming challenges like limited AI literacy and contextual mismatches, highlighting the potential for tailored, impactful education. This study can inform teacher educators, policymakers, administrators, and teachers to integrate AI into their PLCs to develop a PLTE.


Heat transfer enhancement in flow boiling using environmentally safe additives

Abstract: This study represents experimental data for flow boiling. Experiments were conducted over the horizontal and angular section with inner heating element with the downward flow. Bubble dynamics & heat transfer enhancement in flow boiling using saturated water and betel nut solution has been studied experimentally. The concentration of surfactant was taken 400–1,200 ppm. Bubble behavior is observed for different angle of water tube as a nucleation site. The bubble dynamics was studied using SONY Cyber-shot camera operating at 30 frames per second at atmospheric pressure. The result obtained by aqueous solution with and without additives shows dissimilarity between temperature difference, heat fluxes & heat transfer coefficient. The upstream interface of the bubble is found to exhibit both forward and reverse movement during bubble growth. The little effect of gravity on the bubble growth rate by the heater glass tube inclination. The enhancement is observed due to surface tension of the environment accepted additive solution.

Sameer S. Gajghate
Vaibhav Khandekar
Shrikrushna Chopade

Engineering (General). Civil engineering (General)


Machine Learning Model Coupled with Graphical User Interface for Predicting Mechanical Properties of Flax Fiber

Abstract: Machine learning model coupled with graphical user interface was developed to predict mechanical properties of flax fiber. The experiment was conducted using test setup which applies constant rate of loading (CRL). Flax fiber was tested under five independent parameters i.e, type of fiber (Tf), moisture content (Mc), weight of sample (Ws), gauge length (Gl) and loading rate (Lr) with response variables, i.e., breaking load and elongation. In this study, a total of 432 patterns of input and output parameters obtained from laboratory experiments were used to develop machine learning algorithms (Random forest, support vector, and XGBoost). Among the machine learning models, random forest regressor yielded high R2 value, low mean squared error (MSE), and mean absolute error (MAE). The SHapley Additive exPlanations (SHAP) analysis was performed and found sample weight and gauge length were the most influential features for breaking load and elongation, respectively. The developed GUI, integrated with a random forest regressor, predicted breaking load and elongation with an error range of −2.5% to 2.3% for raw fiber and 1.5% to 6.5% for cleaned fiber. The developed GUI coupled random forest regressor can be used to predict the mechanical properties of fibers with ease.

T. Nageshkumar
Prateek Shrivastava
L. Ammayapan
Manisha Jagadale
L. K. Nayak
D. B. Shakyawar
Indran Suyambulingam
P. Senthamaraikannan
R. Kumar

Textile bleaching, dyeing, printing, etc.


Soft computing approach for optimization of turning characteristics of elastomers under different lubrication conditions

Abstract: AbstractElastomers are the class of materials that are widely used in a variety of industrial, commercial, and consumer applications due to their unique mechanical properties, including high elasticity, high flexibility, and high resilience. However, there are many challenges in machining of elastomers such as poor surface finish, build up of heat, degradation of elastomers, etc. To overcome these challenges, cryogenic cooling assistance has been introduced as a means of improving the machinability of elastomers. This paper presents a soft computing approach for optimizing the surface roughness and cutting force during turning of elastomers under different lubrication conditions. Three types of elastomers, namely Nitrile Rubber (NBR), Polyurethane Rubber (PU), and Neoprene Rubber (CR), are studied, and a cryogenic fluid delivery system is employed to improve the machining process. Taguchi’s L27 array is used to vary the input parameters, and a Back-Propagation Artificial Neural Network (BPANN) model is developed to predict the cutting force and surface roughness. The cutting force and surface roughness are analyzed under different cooling conditions, cutting speeds, feeds, and depths of cut for various elastomers. The results show that changes in cutting conditions significantly affect the cutting force and that the type of lubrication used affects the cutting force by altering the material’s physical properties. Cutting force is significantly influenced by cutting conditions, and NBR requires the highest cutting force compared to PU and CR. Further, at a cutting speed of 55 m/min, a feed of 0.11 mm/rev, and a depth of cut of 0.25 mm, the cutting force for NBR (85.1 N), while for PU (75.1 N) and CR (80.3 N), respectively. Finally, with LN2 lubrication conditions, the Cutting Force decreased by 45% and Surface Roughness decreased by 16.9%. This study provides insights into the factors affecting the elastomer machining process, which can be useful for optimizing the machining process parameters and improving machining efficiency.

Malikasab Bagawan
Suresh T. Dundur
Rajesh Gurani
Raviraj Shetty
Rajesh Nayak
S. V. Udaya Kumar Shetty
Madhukara Nayak
Adithya Hegde


Epigenetic alterations in mesenchymal stem cells by osteosarcoma-derived extracellular vesicles

Abstract: Extracellular vesicles (EVs) are central to intercellular communication and play an important role in cancer progression and development. Osteosarcoma (OS) is an aggressive bone tumour, characterized by the presence of malignant mesenchymal cells. The specific tumour-driving genetic alterations that are associated with OS development are currently poorly understood. Mesenchymal stem cells (MSCs) of osteogenic lineage have been postulated as likely candidates as the cells of origin for OS, thus indicating that MSCs and OS stroma cells may be related cell types. Therefore, this study set out to examine the EV-mediated intercellular crosstalk of MSCs and OS. MSCs and pre-osteoblasts were treated with OS-EVs at different time points, and the epigenetic signature of OS-EVs was assessed by methylation analysis of LINE-1 (long interspersed element) and tumour suppressor genes. In addition, surface markers and expression of specific genes were also evaluated. Our data indicated that OS-EVs mediated LINE-1 hypomethylation in MSCs, whereas an opposite effect was seen in pre-osteoblasts, indicating that MSCs but not pre-osteoblasts were susceptible to epigenetic transformation. Thus, OS-EVs modulated the fate of MSCs by modulating the epigenetic status, and also influenced the expression of genes related to bone microenvironment remodelling. Overall, this study provided evidence that epigenetic regulation appears to be an early event in the transformation of MSCs during the development of OS. Elucidating the mechanisms of EV-mediated communication may lead to new avenues for therapeutic exploitation.

Bettina Mannerström
Roman Kornilov
Ahmed G. Abu-Shahba
Iftekhar M. Chowdhury
Snehadri Sinha
Riitta Seppänen-Kaijansinkko
Sippy Kaur


Rapid defect prediction and optimisation method for Ti-modified AlCuMg alloys processed by laser powder-bed fusion

Abstract: Ti-modified AlCuMg alloys have demonstrated great potential in improving the printability and mechanical properties of conventional Al alloys processed by laser powder-bed fusion (LPBF). However, an effective material design method, which considers processing parameters and solidification microstructure, is currently absent. Accordingly, the present work proposed a comprehensive model with which the formation of hot-tearing cracks and lack-of-fusion pores could be more efficiently predicted. The hot-tearing factor was an assistant in the tailoring of crack-free Ti-modified AlCuMg alloys, while the lack-of-fusion factor suggested a volumetric energy density for better printability. This hot-tearing factor could also serve as the supplementary method for evaluating the crack susceptibility of AlCuMg alloys. The microstructure evolution and mechanical properties were also investigated to achieve an optimal processing window for these alloys, which could satisfy the dual requirements of higher mechanical properties and better formability. It was believed that this comprehensive model would facilitate the tailoring of crack-free AlCuMg alloys and the optimisation of processing parameters in a time-efficient manner with high precision.

Ziqian Wang
Yuhan Qian
Tengteng Sun
Yakai Xiao
Zijue Tang
Yi Wu
Hua Sun
Xingtian Liu
Haowei Wang
Hongze Wang


Transactional sex in the wake of COVID-19: sexual and reproductive health and rights of the forcibly displaced

Lauren Jacobson
Alexandra Regan
Shirin Heidari
Monica Adhiambo Onyango

Diseases of the genitourinary system. Urology


Genetic parameters of racing merit of Thoroughbred horses in steeplechase races

Abstract: The aim of this study was to estimate variance components of racing ability in Thoroughbreds involved in steeplechase races. Race results were collected from steeplechase races in France (n=9041), in the United Kingdom and Ireland (n=8314) and contained the results of overall 106 020 runs from 1998 to 2003. Performance was measured by two criteria: earnings and ranks after mathematical transformation. The effects of year, sex, age, and race were considered as fixed, animal, permanent environment and maternal as random. Maternal environmental component for ranks were 0.021 in France and 0.000 in the United Kingdom and Ireland. Estimated heritabilities for the ranking criteria were 0.18 (repeatability 0.33) in France and 0.06 (repeatability 0.19) in the United Kingdom and Ireland. The high genetic correlation between the two traits (0.94 and 0.97) gives the opportunity to find out the most suitable criteria for breeding value estimation.

József Stefler
Bertrand Langlois
Christine Blouin
Árpád Bokor


Stress and coping strategies among youth during the COVID-19 pandemic: a population-based cohort study

Abstract: The COVID-19 pandemic caused a worldwide health- and societal crisis. Youth were exposed to enduring stressors. We examined types and load of stressors faced by youth, and their use of coping strategies. A population-based sample within Bergen municipality, Norway (N = 1031, 11–19 years) completed the Response to Stress Questionnaire 9 months into the pandemic. Social stressors were most frequent, with secondary control engagement being the most used coping strategy. Stress and coping strategies differed depending on sex, age, and socioeconomic status. Heightened stress were associated with primary and secondary control engagement, and disengagement. Thus, youth employed a range of coping strategies to an increasing degree with heightened levels of COVID-19 stress. The frequency of secondary control engagement aligns with the enduring uncontrollable nature of the outbreak. For future health crises, authorities should focus on social stressors experienced by youth, especially among girls, older youth, and youth with low socioeconomic status.

Stine Lehmann
Jens Christoffer Skogen
Gro Mjeldheim Sandal
Ragnhild Bjørknes
Ellen Haug
Lars T. Fadnes
Silje Mæland
Bente Storm Mowat Haugland

International Journal of Adolescence and Youth

Special aspects of education
The family. Marriage. Woman


Convergence rate of principal component analysis with local-linear smoother for functional data under a unified weighing scheme

Abstract: The unified weighing scheme for the local-linear smoother in analysing functional data can deal with data that are dense, sparse or of neither type. In this paper, we focus on the convergence rate of functional principal component analysis using this method. Almost sure asymptotic consistency and rates of convergence for the estimators of eigenvalues and eigenfunctions have been established. We also provide the convergence rate of the variance estimation of the measurement error. Based on the results, the number of observations within each curve can be of any rate relative to the sample size, which is consistent with the earlier conclusions about the asymptotic properties of the mean and covariance estimators.

Xingyu Yan
Xiaolong Pu
Yingchun Zhou
Xiaolei Xun


Effect of urea treatment on the nutritive value of local sorghum and millet straw: a comparative study on growing performance of Djallonke rams

Abstract: Two tons of and chopped millet and sorghum straws have been treated with an urea solution at 5% (100 kg of straw, sprinkled with 50 lt. of solution). Treated straws were used as basic diet (900 g day) associated to 100 g of cotton cake for 24 growing Djallonke rams in comparison to non treated straws. Four groups of animals were fed for 98 days with: urea treated sorghum (UTSS), not treated sorghum straw (NTSS), treated millet (UTMS), non treated millet straw (NTMS). Treated straws presented an increase of NDF of about 9%, of total nitrogen from 2 to 3 times while digestibility of dry matter increased respectively by 8,8% and 23,0% respectively in treated sorghum and millet. Also dry matter intake increased by 4,5% and 15,5% for treated sorghum and millet respectively compared to non treated. Mean weekly weight gain were significantly higher (P<0.05) for UTSS e UTMS compared to NTSS e NTMS. While the weekly weight gain, did not differed between UTSS vs. UTMS and NTSS vs. NTMS. At the end of the trial the UTSS and UTMS group presented a weight gain of about 40% and 38.7%, of their initial weight; while the gain for both NTSS and NTMS was respectively of 31.1% and 29.5%.

A.B. Kanwe
D. De Meneghi
G. Ladetto
M. Tarantola
A. Schiavone
M. Mattoni


Combating fake news, disinformation, and misinformation: Experimental evidence for media literacy education

Abstract: This study investigated the effect of media and information literacy (MIL) on the ability to identify fake news, disinformation and misinformation, and sharing intentions. The experimental approach was selected to study both the control group and experimental group made up of a total of 187 respondents. Comparative analysis of the two groups revealed that although more respondents in the experimental group were able to identify the inauthenticity of information presented to them, some of the respondents in the control group were also able to do the same, even though they did not receive MIL training. Conversely, some respondents in the experimental group, even though they were trained in MIL, could not determine the inauthenticity of information, possibly because the one-off training given to them did not allow them to assimilate all the information in one sitting. Nonetheless, the results of the bivariate correlation computation showed that MIL trained respondents were more likely to determine authenticity or otherwise of information and less likely to share inaccurate stories. This means that when MIL increases, sharing of fake news decreases. This is yet another evidence that MIL enables information consumers to make informed judgments about quality information. It is recommended that MIL is incorporated into mainstream educational modules and consistently revised to reflect the demands of the times. MIL programs must also consider how to effectively reach those without formal education. Actors within the information, communications, and media ecology must contribute to their quota in making information consumers more discerning with the right MIL sensitisation.

History of scholarship and learning. The humanities


The impact of primary care organization on avoidable hospital admissions for diabetes in 23 countries

Abstract: Objective: Diabetes is a so-called ambulatory care sensitive condition. It is assumed that by appropriate and timely primary care, hospital admissions for complications of such conditions can be avoided. This study examines whether differences between countries in diabetes-related hospitalization rates can be attributed to differences in the organization of primary care in these countries. Design: Data on characteristics of primary care systems were obtained from the QUALICOPC study that includes surveys held among general practitioners and their patients in 34 countries. Data on avoidable hospitalizations were obtained from the OECD Health Care Quality Indicator project. Negative binomial regressions were carried out to investigate the association between characteristics of primary care and diabetes-related hospitalizations. Setting: A total of 23 countries. Subjects: General practitioners and patients. Main outcome measures: Diabetes-related avoidable hospitalizations. Results: Continuity of care was associated with lower rates of diabetes-related hospitalization. Broader task profiles for general practitioners and more medical equipment in general practice were associated with higher rates of admissions for uncontrolled diabetes. Countries where patients perceive better access to care had higher rates of hospital admissions for long-term diabetes complications. There was no association between disease management programmes and rates of diabetes-related hospitalization. Hospital bed supply was strongly associated with admission rates for uncontrolled diabetes and long-term complications. Conclusions: Countries with elements of strong primary care do not necessarily have lower rates of diabetes-related hospitalizations. Hospital bed supply appeared to be a very important factor in this relationship. Apparently, it takes more than strong primary care to avoid hospitalizations.Key points Countries with elements of strong primary care do not necessarily have lower rates of diabetes-related avoidable hospitalization. Hospital bed supply is strongly associated with admission rates for uncontrolled diabetes and long-term complications. Continuity of care was associated with lower rates of diabetes-related hospitalization. Better access to care, broader task profiles for general practitioners, and more medical equipment in general practice was associated with higher rates of admissions for diabetes.

Tessa Van Loenen
Marjan J. Faber
Gert P. Westert
Michael J. Van den Berg

Scandinavian Journal of Primary Health Care


REVERSIBLE CORTICAL BLINDNESS FOLLOWING SUCCESSFUL SURGICAL REPAIR OF TWO STAB WOUNDS IN THE HEART

Abstract: This report describes a case of cortical blindness that followed successful surgical repair of two stab wounds in the heart in a 29-year old Libyan man. The patient  presented in a state of pre cardiac arrest (shock and low cardiac output status), following multiple chest stab wounds. Chest tube was immediately inserted. Surgery was urgently performed suturing the two wounds; in the root of the aorta and in the left ventricle, and haemostasis was secured. Cardiac arrest was successfully prevented. The patient recovered smoothly, but 24 hours later he declared total blindness. Ophtalmic and neurological examinations and investigations that included fundoscopy, Electroencephalograms (EEGs) and Computed Tomography Scans revealed no abnormalities, apart from absence of alpha waves in the EEGs. We diagnosed the case as cortical blindness and continued caring for the patient conservatively. Three days later, the patient regained his vision gradually and was discharged on the 7th postoperative day without any remarks.

Zaiton A
Abdul Razeq M
Saad K
El Snaini F
El Gatit A


Genotype and phenotype analysis of α-thalassemia fusion gene in southern China

Abstract: Objective The α-globin fusion gene between the HBA2 and HBAP1 genes, is clinically important in thalassemia screening because this fusion gene can cause severe hemoglobin (Hb) H disease when combined with α0 -thalassemia (α0 -thal). In this study, we evaluate the red blood cell parameters of α-thalassemia fusion gene in southern China.Method Study samples suspected of α-thalassemia fusion gene were collected and confirmed by PCR-sequencing from one medical lab center in southern China. Their genotypes and phenotypes were analyzed.Results A total of 266 cases of α-thalassemia fusion gene were confirmed in our lab from 2017 to 2023, most of them were from Hainan province (169 cases) and Huadu district of Guangzhou (21 cases), the nationality of 143 cases from Hainan was identified, with 71.3% (102/143) being from the Li minority. The Hb, MCV, MCH for αα/(αα)fusion in adult males were 143.5±11.83g/L, 81.51±4.39 fl, and 26.26±1.29 pg, respectively; and in females, they were 126.69±12.89 g/L, 80.10±4.05 fl, 25.8±2.04 pg, respectively. All 12 cases (αα) Fusion/ --SEA showed anemia with decreased Hb, MCV and MCH.Conclusion The carriers of α-globin fusion gene heterozygotes are clinically silent and exhibit an α+ phenotype. Individuals with (αα)Fusion/--SEA show apparent anemia. This α-globin fusion gene is relatively common in southern China, specifically among the Li minority of Hainan province. Therefore, it should be taken into account for genetic counseling purposes.

Yi-Yuan Ge
Yan-Quan Lai
Ai-Ping Ju
Lie-Jun Li
Min Lu
Long-Xu Xie
Min Huang
Li-Ye Yang

Diseases of the blood and blood-forming organs


A single cell survey of the microbial impacts on the mouse small intestinal epithelium

Abstract: The small intestinal epithelial barrier inputs signals from the gut microbiota in order to balance physiological inflammation and tolerance, and to promote homeostasis. Understanding the dynamic relationship between microbes and intestinal epithelial cells has been a challenge given the cellular heterogeneity associated with the epithelium and the inherent difficulty of isolating and identifying individual cell types. Here, we used single-cell RNA sequencing of small intestinal epithelial cells from germ-free and specific pathogen-free mice to study microbe-epithelium crosstalk at the single-cell resolution. The presence of microbiota did not impact overall cellular composition of the epithelium, except for an increase in Paneth cell numbers. Contrary to expectations, pattern recognition receptors and their adaptors were not induced by the microbiota but showed concentrated expression in a small proportion of epithelial cell subsets. The presence of the microbiota induced the expression of host defense- and glycosylation-associated genes in distinct epithelial cell compartments. Moreover, the microbiota altered the metabolic gene expression profile of epithelial cells, consequently inducing mTOR signaling thereby suggesting microbe-derived metabolites directly activate and regulate mTOR signaling. Altogether, these findings present a resource of the homeostatic transcriptional and cellular impact of the microbiota on the small intestinal epithelium.

Derek K.L. Tsang
Ryan J. Wang
Oliver De Sa
Arshad Ayyaz
Elisabeth G. Foerster
Giuliano Bayer
Shawn Goyal
Daniel Trcka
Bibaswan Ghoshal
Jeffrey L. Wrana
Stephen E. Girardin
Dana J. Philpott

Diseases of the digestive system. Gastroenterology


Adolescent pregnancy outcomes in Jos, North Central Nigeria: The roles of disclosure and social support systems

Abstract: ABSTRACTAdolescent pregnancy is mostly unintended and an indicator of unmet sexual and reproductive health (SRH) needs. In most African cultures, sociocultural and religious expectations of chastity make unintended adolescent pregnancy a traumatic experience. This study examined the roles of disclosure and social support networks in determining adolescent pregnancy outcomes in Jos, Nigeria. Using a qualitative design, we conducted in-depth interviews with 17 young persons aged 16–24 years, recruited through purposive and snowballing sampling methods. Data were analysed using an inductive approach. Informal social support networks, mainly mothers and close friends, played prominent roles in pregnancy disclosure. The fear of unsafe abortion complications and lack of other options forced most participants into early motherhood. Parenting issues also contributed to unintended adolescent pregnancies. Participants noted that adolescent males had better access to contraceptive devices like condoms. Additionally, the absence of formal opportunities for institutional support through education and youth-friendly SRH services constituted barriers to preventing unintended adolescent pregnancies. Considering the important role family plays, preventing unintended adolescent pregnancies requires empowering parents on SRH communication. A gender-based approach to adolescent-friendly SRH services is recommended. The Nigerian government needs to reconsider how to provide contextually-acceptable comprehensive sexuality education to young people.

Hannah M. Degge
Comfort Z. Olorunsaiye
Timothy A. Achema
Tina O. Ubanyi
Farida N. Yada


Progressive suppression of regulated cell death defines terminal macrophage states in liver cirrhosis

Abstract: Background Macrophages are central regulators of liver immunity and fibrosis; Recent single-cell studies have characterized macrophage heterogeneity in cirrhosis; however, how regulated cell death programs shape their functional transitions across disease progression in human liver remains poorly defined.Methods We integrated scRNA-seq data from 224,529 cells across 31 adult liver samples to define macrophage states and trajectories. Functional activities of regulated cell death pathways were assessed, and key programs were validated by dual immunofluorescence in human liver tissues.Results Four macrophage subsets with disease-biased distributions were identified. Cirrhotic macrophages exhibited progressive suppression of autophagy, necroptosis, apoptosis, and immunogenic cell death along differentiation, most prominently in terminal states, accompanied by transcriptional exhaustion and reduced immune regulator expression. A disease-associated transitional subpopulation displayed hybrid metabolic–immune features and yielded a six-gene diagnostic signature (LDHB, CD37, S100A10, RNASE1, CXCR4 and CORO1A) validated in bulk RNA-seq data (AUC = 0.936). Spatial analyses confirmed attenuation of autophagy and necroptosis and enrichment of CXCR4- and S100A10-positive macrophages in fibrotic niches.Conclusion Human cirrhosis is characterized by progressive repression of regulated cell death programs in liver macrophages, providing mechanistic insight into disease progression and identifying macrophage-associated molecular signatures that may aid in patient stratification and serve as potential targets for future therapeutic intervention.

Kepu Zheng
Leiyang Dai
Yanghui Wen
Haitao Jiang
Yang Gao
Feng Ren
Yu Tang
Xiang Huang
Jianghua Ran
Yunjie Chen


Spectral efficiency of adaptive OFDM systems over high mobility Nakagami-m fading channels

Abstract: In this paper, we investigate the impact of rate and power adaptation (RPA) and rate adaptation (RA) using square M-ary quadrature amplitude modulation (MQAM) on the average spectral efficiency (ASE) of orthogonal frequency division multiplexing (OFDM) systems under instantaneous bit-error-rate (BER) constraint over high mobility Nakagami multipath fading (NMF) channels. Especially, the closed-form expressions for the average spectral efficiency (ASE) of RPA and RA are obtained when these adaptive schemes are used over NMF channels with existence inter-carrier interference (ICI) caused by the high mobility. By comparing the ASE of RPA and RA under different number of subcarriers, a simplified rate and subcarriers bandwidth adaptation (RSBA) algorithm is obtained. Simulation results indicate that RSBA is more suitable for high-speed communication environment than RA.

Control engineering systems. Automatic machinery (General)


Unraveling the mediating role of plant color and familiarity on children’s mood in urban landscape

Abstract: An important element of urban landscapes is various plants, and contact with urban landscapes can promote children’s positive mood and mental health. However, few studies focus on Asian school-aged children’s mood for different urban landscapes and the factors shaping them. This study attempted to understand the variables, including plant color, familiarity, and viewing distances (setting 0 m and 2 m), using 150 landscape scenes (68 flowering plants, 50 exotic plants, and 32 foliage plants), on the effects of the landscape preferences and mood states of 119 school-aged children (55 boys and 64 girls). Then, using partial least squares path modelling analysis to display the gender difference in children’s color perception, landscape preferences, and mood states. The results show that: (1) Plant color richness, familiarity, and the proportion of non-green parts of scenes positively affected children’s mood states. (2) Flowering plants are more likely to produce positive moods than those of exotic plants and foliage plants. (3) Plant color richness and familiarity significantly and positively correlated with children’s mood states and landscape preferences. (4) Notably, gender differences exist in children’s landscape preferences and mood states. This study underscores the importance of plant color collocation in child-friendly landscapes and considers the gender differences in urban landscape policy decisions. Besides, adding flowering plants and native plants in urban landscapes may potentially enhance children’s mood state and urban green space utilization rate.

Journal of Asian Architecture and Building Engineering


Forecasting Crude Oil Price and Stock Price by Jump Stochastic Time Effective Neural Network Model

Abstract:
The interacting impact between the crude oil prices and the stock market indices
in China is investigated in the present paper, and the corresponding statistical
behaviors are also analyzed. The database is based on the crude oil prices of Daqing
and Shengli in the 7-year period from January 2003 to December 2009 and also
on the indices of SHCI, SZCI, SZPI, and SINOPEC with the same time period. A
jump stochastic time effective neural network model is introduced and applied to
forecast the fluctuations of the time series for the crude oil prices and the stock
indices, and we study the corresponding statistical properties by comparison. The
experiment analysis shows that when the price fluctuation is small, the predictive
values are close to the actual values, and when the price fluctuation is large, the
predictive values deviate from the actual values to some degree. Moreover, the
correlation properties are studied by the detrended fluctuation analysis, and the
results illustrate that there are positive correlations both in the absolute returns of
actual data and predictive data.


Contributions From the New Mexico Agricultural Experiment Station: I. New North American Coccidae


Integrability of Reeb Distribution Associated to a Generalized Engel Manifold

Abstract: In this paper, we define a generalized Reeb distribution of an Engel 4n-manifold and give a necessary and sufficient condition for integrability of this Reeb distribution which gives a generalization of some results of N. Pia about Reeb distributions of Engel 4-manifolds. Before that, we detailed explicit standard examples of Engel structure coming from the Cartan prolongation of some contact 3-manifolds and 5-manifolds.

Serigne Abdoul Aziz Dramé
Cheikh Khoule
Hamidou Dathe


Spectroscopic Methods of Edible Flower Authentication and Quality Control for Food Applications

Abstract: ABSTRACT The global demand for edible flowers has increased due to their diverse applications in food, nutraceuticals, and the medical field. However, issues of species identification, adulteration, contamination, and quality necessitate the use of advanced methods to authenticate product quality for edible flowers. Conventional methods are expensive, time‐consuming, and require highly skilled personnel and technical expertise. Spectroscopic methods, including Fourier transform infrared, near‐infrared, and Raman spectroscopy, are efficient, fast, and non‐destructive, providing rapid insight into the chemical structure and authenticity of edible flowers. This review systematically summarizes the recent advances in spectroscopic methods for authenticating edible flowers, including the detection of chemical changes and ensuring product integrity. The primary goal is to examine the applications of spectroscopic techniques for assessing quality changes in edible flowers during processing for food applications. Spectroscopic techniques, such as FT‐IR, NIR, and Raman spectroscopy, are rapid, accurate, and non‐destructive alternatives for authenticating the composition and quality of edible flowers. These methods enable the detection of bioactive compounds, differentiation of species, and identification of adulterants with minimal sample processing. Furthermore, chemometric models enhance data analysis, allowing for automated classification and real‐time quality monitoring of edible flowers.

Fidele Benimana
Christopher Kucha
Anupam Roy
Anand Mohan

Food processing and manufacture
Toxicology. Poisons


Existence of Three Positive Solutions to Some p-Laplacian Boundary Value Problems

Abstract: We obtain, by using the Leggett-Williams fixed point theorem, sufficient conditions that ensure the existence of at least three positive solutions to some p-Laplacian boundary value problems on time scales.

Moulay Rchid Sidi Ammi
Delfim F. M. Torres


Optimization of Support and Relief Parameters for Deep-Buried Metal Mine Roadways

Abstract: The management of rock mass deformation in high-stress roadways is a pivotal aspect of deep geotechnical engineering. Given the fruitful outcomes of research in rock mechanics regarding traditional confining pressure control methods, scholars have increasingly turned their attention to exploring pressure-relieving techniques, including borehole pressure relief and blasting pressure relief. However, there is limited research on pressure relief methods for deep-buried hard rock tunnels. This article commences with an overview of pressure relief in the roadway and conducts a detailed study on the parameters and methods of pressure relief in the roadway. To address safety and mining efficiency challenges, such as severe deformation leading to support failures, this study conducted a parameter analysis using the Sanshandao Gold Mine as a case study. Based on existing support methods, a strategy for arranging pressure relief roadways at varying distances from the main roadway is proposed, significantly enhancing the stress environment there. Numerical simulation software was employed to model two scenarios: (1) excavating the pressure relief roadway, main roadway, and maintenance roadway simultaneously and (2) first excavating the pressure relief roadway, followed by the main roadway and the maintenance roadway simultaneously. Simulation results indicated that the first pressure relief approach outperforms the second. The optimal position for both pressure relief roadways is 15 m from the main roadway, resulting in maximum deformation of the main roadway within 100 mm. These findings align with on-site stress monitoring data and satisfy safety production criteria. The research offers a theoretical foundation for similar pressure relief techniques in deeply buried, high-stress roadways.

MingWei Jiang
YuYun Fan
WeiWei Su
Jincheng Wang
Ming Lan
Qibin Lin


Chronic Pulmonary Aspergillosis Complicating Bronchial Atresia

Abstract: Bronchial atresia is a rare pulmonary developmental anomaly characterized by the presence of a focal obliteration of a segmental or lobar bronchial lumen. The lung distal to the atretic bronchus is typically emphysematous along with the presence of mucus filled ectatic bronchi (mucoceles). BA is usually asymptomatic but pulmonary infections can rarely develop in the emphysematous lung distal to the atretic bronchus. We present a unique case of chronic pulmonary aspergillosis (CPA) in a patient with BA with no evidence of immune dysfunction. The patient was treated initially with voriconazole and subsequently underwent surgical excision of the involved area. On follow-up, she has done extremely well with no evidence for recurrence. In summary, we describe the first case of chronic pulmonary aspergillosis in an immunocompetent patient with bronchial atresia.

Mazen O. Al-Qadi
Dereddi Raja S. Reddy
Brandon T. Larsen
Vivek N. Iyer


Synchronous Multicentric Giant Cell Tumour of Distal Radius and Sacrum with Pulmonary Metastases

Abstract: Giant cell tumour (GCT) is an uncommon primary bone tumour, and its multicentric presentation is exceedingly rare. We report a case of a 45-year-old female who presented to us with GCT of left distal radius. On the skeletal survey, osteolytic lesion was noted in her right sacral ala. Biopsy confirmed both lesions as GCT. Pulmonary metastasis was also present. Resection-reconstruction arthroplasty for distal radius and thorough curettage and bone grafting of the sacral lesion were done. Multicentric GCT involving distal radius and sacrum with primary sacral involvement is not reported so far to our knowledge.

Varun Sharma Tandra
Krishna Mohan Reddy Kotha
Moorthy Gadisetti Venkata Satyanarayana
Kali Varaprasad Vadlamani
Vyjayanthi Yerravalli


Recent Applications of Electrospun Nanofibrous Scaffold in Tissue Engineering

Abstract: Tissue engineering is a relatively new area of research that combines medical, biological, and engineering fundamentals to create tissue-engineered constructs that regenerate, preserve, or slightly increase the functions of tissues. To create mature tissue, the extracellular matrix should be imitated by engineered structures, allow for oxygen and nutrient transmission, and release toxins during tissue repair. Numerous recent studies have been devoted to developing three-dimensional nanostructures for tissue engineering. One of the most effective of these methods is electrospinning. Numerous nanofibrous scaffolds have been constructed over the last few decades for tissue repair and restoration. The current review gives an overview of attempts to construct nanofibrous meshes as tissue-engineered scaffolds for various tissues such as bone, cartilage, cardiovascular, and skin tissues. Also, the current article addresses the recent improvements and difficulties in tissue regeneration using electrospinning.

Hamza Abu Owida
Jamal I. Al-Nabulsi
Feras Alnaimat
Muhammad Al-Ayyad
Nidal M. Turab
Ashraf Al Sharah
Murad Shakur


Modeling Rare Species Distribution at the Edge: The Case for the Vulnerable Endemic Pyrenean Desman in France

Abstract: The endemic Pyrenean Desman (Galemys pyrenaicus) is an elusive, rare, and vulnerable species declining over its entire and narrow range (Spain, Portugal, France, and Andorra). The principal set of conservation measures in France is a 5-years National Action Plan based on 25 conservation actions. Priority is given to update its present distribution and develop tools for predictive distribution models. We aim at building the first species distribution model and map for the northern edge of the range of the Desman and confronting the outputs of the model to target conservation efforts in the context of environmental change. Contrasting to former comparable studies, we derive a simpler model emphasizing the importance of factors linked to precipitation and not to the temperature. If temperature is one of the climate change key factors, depicted shrinkage in Desman distribution could be lower or null at the northern (French) edge suggesting thus a major role for this northern population in terms of conservation of the species. Finally, we question the applied issue of temporal and spatial transferability for such environmental favourability models when it is made at the edge of the distribution range.

M. Williams-Tripp
F. J. N. D'Amico
C. Pagé
A. Bertrand
M. Némoz
J. A. Brown


Changes of Retina Are Not Involved in the Genesis of Visual Hallucinations in Parkinson’s Disease

Abstract: Parkinson’s disease (PD) is characterized by motor and nonmotor symptoms. Nonmotor symptoms include primarily visual hallucinations (VH). The aim of our study was to establish whether patients with PD and visual hallucinations (PDH+) have structural changes of retina detected by an optical coherence tomography (OCT) in comparison with PD patients without visual hallucinations (PDH−). We examined 52 PD patients (18 with VH, 34 without VH) and 15 age and sex matched healthy controls. Retinal nerve fiber layer (RNFL) thickness and macular thickness and volume were assessed by OCT. Functional impairment of retina was assessed using 2.5% contrast sensitivity test. For OCT outcomes we analyzed 15 PDH+ and 15 PDH− subjects matched for age, gender, and PD duration. For contrast sensitivity we analyzed 8 pairs of patients matched for age, gender, and visual acuity. There was no significant difference in RNFL thickness and macular thickness and macular volume between 15 PDH+ and 15 PDH− subjects, and also between a group of 44 PD patients (both PDH+ and PDH−) and 15 age and gender matched healthy controls. No significant difference was found for 2.5% contrast sensitivity test values between PDH+ and PDH− subjects. Therefore we conclude that functional and structural changes in retina play no role in genesis of VH in PD.

Aleš Kopal
Eva Mejzlíková
Jana Lízrová Preiningerová
David Brebera
Olga Ulmanová
Edvard Ehler
Jan Roth

Neurology. Diseases of the nervous system


Shocklets and Short Large Amplitude Magnetic Structures (SLAMS) in the High Mach Foreshock of Venus

Abstract: Abstract Shocklets and short large‐amplitude magnetic structures (SLAMS) are steepened magnetic fluctuations commonly found in Earth's upstream foreshock. Here we present Venus Express observations from the 26th of February 2009 establishing their existence in the steady‐state foreshock of Venus, building on a past study which found SLAMS during a substantial disturbance of the induced magnetosphere. The Venusian structures were comparable to those reported near Earth. The 2 Shocklets had magnetic compression ratios of 1.23 and 1.34 with linear polarization in the spacecraft frame. The 3 SLAMS had ratios between 3.22 and 4.03, two of which with elliptical polarization in the spacecraft frame. Statistical analysis suggests SLAMS coincide with unusually high solar wind Alfvén mach‐number at Venus (12.5, this event). Thus, while we establish Shocklets and SLAMS can form in the stable Venusian foreshock, they may be rarer than at Earth. We estimate a lower limit of their occurrence rate of ≳14%.

Glyn A. Collinson
Heli Hietala
Ferdinand Plaschke
Tomas Karlsson
Lynn B. Wilson III
Martin Archer
Markus Battarbee
Xochitl Blanco‐Cano
Cesar Bertucci
David Long
Merav Opher
Nick Sergis
Claire Gasque
Terry Liu
Savvas Raptis
Sofia Burne
Rudy Frahm
Tielong Zhang
Yoshifumi Futaana


Myocardial Infarction in a Young Female with Palindromic Rheumatism: A Consequence of Negative Remodeling

Abstract: Palindromic rheumatism is a rare disease associated with systemic inflammation. Negative or constrictive coronary artery remodeling is typically not seen until the 7th or 8th decade of life. We report a case of a young female with palindromic rheumatism who suffered a non-ST segment elevation myocardial infarction secondary to a flow-limiting lesion that demonstrated negative remodeling by intravascular ultrasound (IVUS).

Timothy R. Larsen
Sachin Kumar Amruthlal Jain
Jamal Zarghami
Shukri David


Outcomes of Peripheral Vascular Interventions in Select Patients With Lower Extremity Acute Limb Ischemia

Abstract: BackgroundContemporary data on patients presenting with acute limb ischemia (ALI), who are selected for treatment with endovascular peripheral vascular interventions (PVI), are limited. Our study examined outcomes following endovascular PVI in patients with ALI by comparing with patients treated for chronic critical limb ischemia using a regional quality improvement registry. Methods and ResultsOf the 11 035 patients in the Vascular Study Group of New England PVI database (2010–2014), we identified 365 patients treated for lower extremity ALI who were 5:1 frequency matched (by procedure year and arterial segments treated) to 1808 patients treated for critical limb ischemia. ALI patients treated with PVI had high burden of atherosclerotic risk factors and were more likely to have had prior ipsilateral revascularizations. ALI patients were less likely to be treated with self‐expanding stents and more likely to undergo thrombolysis than patients with critical limb ischemia. In multivariable analysis, ALI was associated with higher technical failure (odds ratio 1.7, 95% confidence interval, 1.1%–2.5%), increased rate of distal embolization (odds ratio 2.7, 95% confidence interval, 1.5%–4.9%), longer length of stay (means ratio 1.6, 95% confidence interval, 1.4%–1.8%), and higher in‐hospital mortality (odds ratio 2.8, 95% confidence interval, 1.3%–5.9%). ALI was not associated with risk of major amputation or mortality at 1 year. ConclusionsIn a multicenter cohort of patients treated with PVI, we found that ALI patients selected for treatment with endovascular techniques experienced greater short‐term adverse events but similar long‐term outcomes as their critical limb ischemia counterparts. Further studies are needed to refine the selection of ALI patients who are best served by PVI.

Elica Inagaki
Alik Farber
Jeffrey A. Kalish
Mohammad H. Eslami
Jeffrey J. Siracuse
Robert T. Eberhardt
Denis V. Rybin
Gheorghe Doros
Naomi M. Hamburg

Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease

Diseases of the circulatory (Cardiovascular) system


Marketing Resource Allocation Strategy Optimization Based on Dynamic Game Model

Abstract: Game theory has become an important tool to study the competition between oligopolistic enterprises. After combing the existing literature, it is found that there is no research combining two-stage game and nonlinear dynamics to analyze the competition between enterprises for advertising. Therefore, this paper establishes a two-stage game model to discuss the effect of the degree of firms’ advertising input on their profits. And the complexity of the system is analyzed using nonlinear dynamics. This paper analyzes and studies the dynamic game for two types of application network models: data transmission model and transportation network model. Under the time-gap ALOHA protocol, the noncooperative behavior of the insiders in the dynamic data transmission stochastic game is examined as well as the cooperative behavior. In this paper, the existence of Nash equilibrium and its solution algorithm are proved in the noncooperative case, and the “subgame consistency” of the cooperative solution (Shapley value) is discussed in the cooperative case, and the cooperative solution satisfying the subgame consistency is obtained by constructing the “allocation compensation procedure.” The cooperative solution is obtained by constructing the “allocation compensation procedure” to satisfy the subgame consistency. In this paper, we propose to classify the packets transmitted by the source nodes, and by changing the strategy of the source nodes at the states with different kinds of packets, we find that the equilibrium payment of the insider increases in the noncooperative game with the addition of the “wait” strategy. In the transportation dynamic network model, the problem of passenger flow distribution and the selection of service parameters of transportation companies are also studied, and a two-stage game theoretical model is proposed to solve the equilibrium price and optimal parameters under Wardrop’s criterion.


A Sea Ice Entrapment Event in the Southern Chukchi Sea: Analysis and Prediction

Abstract: Abstract Amplified Arctic warming is reducing sea ice cover, which is driving an increase in geopolitical interest in the region as it offers the possibility of reducing shipping times between Asia, Europe, and eastern North America, at the risk of increased ice hazards. Here, we examine the case of the Norseman II research ship that was trapped by sea ice in the southern Chukchi Sea for 14 days in June 2024. This is the first study of its sort in this region. We show that anomalously thick and extensive sea ice was present north of the region prior to the event, and that strong northerly winds in early June advected this ice southward, trapping the ship. Later in June, southerly winds advected ice northwards away from the ship, helping to free it. We further show that the event was forecastable.

G. W. K. Moore
Michael Steele
Jinlun Zhang
Axel J. Schweiger
Thomas J. Ballinger
Irina Trukhanova
Michael Lawson
William S. Beatty
Scott Hameister


Vibration and Stability of 3000-hp, Titanium Chemical Process Blower

Abstract: This 74-in-diameter blower had an overhung rotor design of titanium construction, operating at 50 pounds per square inch gauge in a critical chemical plant process. The shaft was supported by oil-film bearings and was directdriven by a 3000-hp electric motor through a metal disk type of coupling. The operating speed was 1780 rpm. The blower shaft and motor shaft motion was monitored by Bently Nevada proximity probes and a Model 3100 monitoring system.

International Journal of Rotating Machinery


Demand response potential evaluation based on feature fusion with expert knowledge and multi‐image

Abstract: Abstract Potential evaluation to assist demand response decisions has garnered significant attention with the development of new power systems. However, existing data‐driven methods are challenging to properly exploit multivariate features and the process of response potential evaluation is unclear. Therefore, the authors propose an evaluation method that fuses expert features with multi‐image inputs and analyses the model evaluation process based on gradient. First, typical load profiles are extracted by the proposed procedure. Next, features derived from expert knowledge are calculated from the perspectives of adjustability, regularity, and sensitivity of electricity usage. Additionally, the typical load profile's recurrence plot, Markov leapfrog field, and Gramian angle field are created and incorporated into the colourful image as inputs. Then, the evaluation results are obtained by a two‐stream neural network fusing multivariate features. In the experiments, the proposed method is validated and discussed by comparing with many existing methods using London household users' data under the time‐of‐use price, providing new insights for demand response potential evaluation.

Jiale Liu
Xinlei Cai
Zijie Meng
Xin Jin
Zhangying Cheng
Tingzhe Pan

Electrical engineering. Electronics. Nuclear engineering


On Intuitionistic Fuzzy Filters of Intuitionistic Fuzzy Coframes

Abstract: Frame theory is the study of topology based on its open set lattice, and it was studied extensively by various authors. In this paper, we study  quotients of intuitionistic fuzzy filters of an intuitionistic fuzzy coframe. The quotients of intuitionistic fuzzy filters are shown to be filters of the given intuitionistic fuzzy coframe. It is shown that the collection of all intuitionistic fuzzy filters of a coframe and the collection of all intutionistic fuzzy quotient filters of an intuitionistic fuzzy filter are coframes.


Burrowing behavior and burrowing energetics of a bioindicator under human disturbance

Abstract: Abstract Bioindicator species are extensively used for rapid assessment of ecological changes. Their use commonly focuses on changes in population abundance and individual sizes in response to environmental change. These numerical and demographic shifts likely have behavioral and physiological mechanistic drivers that, if understood, could provide additional insights into the use of these species as bioindicators of habitat health. The Atlantic ghost crab, Ocypode quadrata, is a global bioindicator species of human disturbance on sandy shores. Individual size and population abundance of O. quadrata decline dramatically at sites with human disturbance, and the causes of this phenomenon remain unclear. Here, we test the hypothesis that individual and population‐level changes at disturbed sites reflect changes in burrowing behavior and energetics. Specifically, we examine whether or not the burrowing behavior (e.g., burrow fidelity and longevity) of O. quadrata changes because of human disturbance. We also examine energy required for burrowing by O. quadrata across different levels of human disturbance. We show that O. quadrata have the highest burrow fidelity and longevity at sites with low level of human impact, and weakest burrow fidelity and longevity at pristine sites. O. quadrata reduce the burrowing energy allocation by manipulating the burrow dimension and increasing the burrow longevity even under low levels of human disturbance. Overall, this study shows that human disturbances not only change the behavior of organisms, but also shift energetic balance. Our results support the use of a bioenergetic approach to better understand how human disturbances influence natural populations, and the specific use of this approach with this bioindicator species.


Sub-THz Characterisation of Monolayer Graphene

Abstract: We explore the optical and electrical characteristics of monolayer graphene by using pulsed optoelectronic terahertz time-domain spectroscopy in the frequency range of 325–500 GHz based on fast direct measurements of phase and amplitude. We also show that these parameters can, however, be measured with higher resolution using a free space continuous wave measurement technique associated with a vector network analyzer that offers a good dynamic range. All the scattering parameters (both magnitude and phase) are measured simultaneously. The Nicholson-Ross-Weir method is implemented to extract the monolayer graphene parameters at the aforementioned frequency range.

Ehsan Dadrasnia
Sujitha Puthukodan
Vinod V. K. Thalakkatukalathil
Horacio Lamela
Guillaume Ducournau
Jean-Francois Lampin
Frédéric Garet
Jean-Louis Coutaz


Current Status of Fasciolosis of Goat in Sylhet, Bangladesh: An Integrated Morphomolecular Study

Abstract: Epidemiological information and proper identification of Fasciola species present in Bangladesh are important for control. This study was aimed at determining the prevalence of liver fluke infection of goats in Sylhet, Bangladesh, and identifying those using integrated morphometric and molecular techniques. A total of 260 slaughtered goats (Capra hircus) were examined, and flukes were collected from infected liver using sterilized forceps. Fasciolosis prevalence in goats was 35.38% (92/260) across all age and sex categories. Female goats were found more infected (37.14%, 65/175) than male goats (31.76%, 27/85), while infection rate was found higher in young animals (37.91%, 69/182) compared to adults (29.48% 23/78). Infection rate was observed higher in rainy season (52.96%, 45/85), followed by winter (27.38%, 26/95) and summer (26.25%, 21/80). Collected flukes were examined by light microscopy after being stained with Semichon’s acetocarmine, and sequences of mtDNA Cox1 genes were obtained. Ten adult flukes were measured, 38.72±3.37 mm in length and 11.8±1.9 mm in width. Based on morphometric features especially branching of the testis and body length/body width ratios (3.28±0.42), the flukes were primarily identified as Fasciola gigantica. Amplicon sequences were compared by BLAST and the cox1 sequences showed 97.1-99.3% similarity with the reference sequences (F. gigantica and Fasciola sp.) from GenBank. In this study, we found a considerable prevalence of fascioliasis in goats, and F. gigantica was solely identified with variation. To control these parasites and prevent potential public health risks, appropriate control techniques must be developed.

Chamali Akter Shykat
Saiful Islam
Foyez Ahmed
Kazi Mehetazul Islam
Jamal Uddin Bhuiyan
Tilak Chandra Nath


P415: TARGETED 3RD-GENERATION (NANOPORE) SEQUENCING REVEALS MANY NOVEL CIRCULAR RNAS OF THE APOPTOSIS-RELATED BCL2L12 GENE, EXPRESSED IN HUMAN CELLS FROM ACUTE MYELOID LEUKEMIA AND MYELODYSPLASTIC SYNDROMES

K. Xenou
C. Sotiropoulou
P. Karousi
N. Machairas
A. Scorilas
V. Pappa
S. Papageorgiou
C. Kontos


Efficacy of heel lifts versus calf muscle eccentric exercise for mid-portion Achilles tendinopathy (the HEALTHY trial): study protocol for a randomised trial

Abstract: Abstract Background Mid-portion Achilles tendinopathy is a common musculoskeletal condition characterised by degeneration of the Achilles tendon, which causes pain and disability. Multiple non-surgical treatments have been advocated for this condition including calf muscle eccentric exercise and in-shoe heel lifts. Although adherence is challenging, there is evidence to suggest that calf muscle eccentric exercise is effective in decreasing pain and improving function in people with Achilles tendinopathy. Heel lifts reduce ankle joint dorsiflexion and Achilles tendon strain, however their efficacy in the management of Achilles tendinopathy is unclear. This article describes the design of a parallel-group randomised trial comparing the efficacy of heel lifts to calf muscle eccentric exercise for Achilles tendinopathy. Methods Ninety-two participants with Achilles tendinopathy will be randomised to one of two groups: (i) a heel lift group that will receive pre-fabricated 12 mm in-shoe heel lifts (Clearly Adjustable®), or (ii) an exercise group that will be advised to carry out a calf muscle eccentric exercise program (twice a day, 7 days a week, for 12 weeks). Outcome measures will be obtained at baseline, 2, 6 and 12 weeks; the primary endpoint for assessing efficacy being 12 weeks. The primary outcome measure will be the total score of the Victorian Institute of Sport Assessment – Achilles (VISA–A) questionnaire. Secondary outcome measures will include thickness and integrity of the Achilles tendon (using ultrasound tissue characterisation [UTC]), participant perception of treatment effect on pain and function (using the 7-point Patient Global Impression of Change scale), severity of pain at the Achilles tendon (using a 100 mm visual analogue scale) in the previous week, health status (using the EuroQol-5D-5L™ questionnaire), physical activity levels (using the 7-day Recall Physical Activity Questionnaire) and calf muscle function (using the standing heel rise test). Data will be analysed using the intention to treat principle. Discussion The HEALTHY trial (Heel lifts versus calf muscle eccentric Exercise for AchiLles TendinopatHY) is the first randomised trial to compare the efficacy of heel lifts to calf muscle eccentric exercise in reducing pain and improving function in people with Achilles tendinopathy. A pragmatically designed trial was developed to ensure that if the interventions are found to be effective, the findings can be readily implemented in clinical practice. Trial registration Australian New Zealand Clinical Trials Registry: ACTRN12617001225303. Registered on August 22nd, 2017.

Chantel L. Rabusin
Hylton B. Menz
Jodie A. McClelland
Angela M. Evans
Karl B. Landorf
Peter Malliaras
Sean I. Docking
Shannon E. Munteanu


Immunological and Viral Profiles of Squamous Cell Carcinoma in Transplant and Non‐Transplant Patients in Singapore

Abstract: ABSTRACT Background Cutaneous squamous cell carcinoma (cSCC) remains poorly understood at the molecular level, both in the immunocompetent and immunosuppressed population with skin of colour. Data on the diversity of viruses found in cSCC is also lacking. Objectives We aimed to characterise the immunological and molecular profiles of cSCC in organ transplant recipients (OTR) and non‐transplant recipients in an Asian cohort (n = 53) and explore the diversity of viruses detected. Methods Gene expression analysis was performed on snap‐frozen cSCC tissues using the NanoString PanCancer IO360 panel. Viral detection was performed using the Twist Comprehensive Viral Research Panel. Results cSCC presented dysregulation of immune response pathways and tumour microenvironment remodelling compared to adjacent normal skin tissue. Cell‐type profiling based on gene expression profiles showed higher levels of exhausted CD8 cells, neutrophils, and cytotoxic cells in tumour cells. Furthermore, three distinct clusters of cSCC gene signatures could be observed, where Cluster 3 with the highest Tumour inflammation signature (TIS) scores displayed distinct upregulation of most pathways suggesting a more inflamed or “hot” tumour phenotype. cSCC of OTR exhibited greater expression of tumour markers (AQP9, SERPINA1) and reduced expression of T‐cell cytokines (CXCL10, CXCL11). Viruses were particularly enriched in tumour tissue, as compared with normal skin. In addition, there was an enrichment of detectable viruses in transplant‐associated cSCC, with several tumours harbouring multiple viruses (HPV, EBV, MCV, and TTV). Conclusions cSCC is marked by a pro‐tumorigenic immune environment with altered immune cell populations. These findings support the potential for stratified, immune‐tailored treatment approaches for cSCC, especially in OTR who have a higher disease burden. Future studies on the possible oncogenic role of the detected viruses can be undertaken.

Choon Chiat Oh
Boon Yee Lim
Elizabeth Chun Yong Lee
Bavani Kannan
Po Yin Tang
Tun Kiat Ko
Clara Wei Teng Koh
Kuan Rong Chan
Jason Yongsheng Chan


A Liquid-Based Cytology System, without the Use of Cytocentrifugation, for Detection of Podocytes in Urine Samples of Patients with Diabetic Nephropathy

Abstract: Objective. Podocytes have highly differentiated functions and are extremely difficult to grow; thus, damage of podocytes is associated with glomerular dysfunction. Desquamated podocytes can be detected in urine of patients with severe renal impairment. Unlike the rapidly progressive glomerular damage in glomerulonephritis, only a few desquamated podocytes are usually detected in diabetic nephropathy (DN). It is not clear whether the low podocyte count in DN is due to limitation of the conventional method or true pathological feature. The aim of this study was to compare the conventional method with a newly modified method in detecting podocytes in morning urine samples of patients with DN. Materials and Methods. The study subjects were patients with type 2 diabetes. Urine samples from these patients were analyzed by the conventional method (Cytospin®) and the modified method (SurePath™). We determined the rate of detection of urinary podocytes and the number of detected cells. Results. The detection rate and podocyte count were significantly higher by the modified method than by the conventional method. The differences in the detection rates and numbers of podocytes were not significant between patients with normoalbuminuria and those with macroalbuminuria. However, they were significant in patients with microalbuminuria. The number of podocytes in the urine correlated significantly with the albumin-to-creatinine ratio, but not with the estimated glomerular filtration rate. Conclusions. The true number of urinary podocytes, as measured by the modified SurePath™-based method, in patients with DN is much higher than that estimated by the conventional method.

Moritsugu Kimura
Masao Toyoda
Nobumichi Saito
Noriko Kaneyama
Han Miyatake
Eitaro Tanaka
Hirotaka Komaba
Masanori Hara
Masafumi Fukagawa

Diseases of the endocrine glands. Clinical endocrinology


Developments and future prospects of personalized medicine in head and neck squamous cell carcinoma diagnoses and treatments

Abstract: Abstract Background Precision healthcare has entered a new era because of the developments in personalized medicine, especially in the diagnosis and treatment of head and neck squamous cell carcinoma (HNSCC). This paper explores the dynamic landscape of personalized medicine as applied to HNSCC, encompassing both current developments and future prospects. Recent Findings The integration of personalized medicine strategies into HNSCC diagnosis is driven by the utilization of genetic data and biomarkers. Epigenetic biomarkers, which reflect modifications to DNA that can influence gene expression, have emerged as valuable indicators for early detection and risk assessment. Treatment approaches within the personalized medicine framework are equally promising. Immunotherapy, gene silencing, and editing techniques, including RNA interference and CRISPR/Cas9, offer innovative means to modulate gene expression and correct genetic aberrations driving HNSCC. The integration of stem cell research with personalized medicine presents opportunities for tailored regenerative approaches. The synergy between personalized medicine and technological advancements is exemplified by artificial intelligence (AI) and machine learning (ML) applications. These tools empower clinicians to analyze vast datasets, predict patient responses, and optimize treatment strategies with unprecedented accuracy. Conclusion The developments and prospects of personalized medicine in HNSCC diagnosis and treatment offer a transformative approach to managing this complex malignancy. By harnessing genetic insights, biomarkers, immunotherapy, gene editing, stem cell therapies, and advanced technologies like AI and ML, personalized medicine holds the key to enhancing patient outcomes and ushering in a new era of precision oncology.

Ratupaskatiye Gedara Gunaratnege Roshan Pradeep

Rajapakse Mudiyanselage Gamini Rajapakse


En bloc release of MVB-like small extracellular vesicle clusters by colorectal carcinoma cells

Abstract: Small extracellular vesicles (EVs) are membrane enclosed structures that are usually released from cells upon exocytosis of multivesicular bodies (MVBs) as a collection of separate, free EVs. In this study, we analysed paraffin embedded sections of archived human colorectal cancer samples. We studied 3D reconstructions of confocal microscopic images complemented by HyVolution and STED imaging. Unexpectedly, we found evidence that large, MVB-like aggregates of ALIX/CD63 positive EV clusters were released en bloc by migrating tumour cells. These structures were often captured with partial or complete extra-cytoplasmic localization at the interface of the plasma membrane of the tumour cell and the stroma. Their diameter ranged between 0.62 and 1.94 μm (mean±S.D.: 1.17 ± 0.34 μm). High-resolution 3D reconstruction showed that these extracellular MVB-like EV clusters were composed of distinguishable internal particles of small EV size (mean±S.D.: 128.96 ± 16.73 nm). In vitro, HT29 colorectal cancer cells also showed the release of similar structures as confirmed by immunohistochemistry and immune electron microscopy. Our results provide evidence for an en bloc transmission of MVB-like EV clusters through the plasma membrane. Immunofluorescent-based detection of the MVB like small EV clusters in archived pathological samples may represent a novel and unique opportunity which enables analysis of EV release in situ in human tissues.

Gábor Valcz
Edit I. Buzás
Ágnes Kittel
Tibor Krenács
Tamás Visnovitz
Sándor Spisák
György Török
László Homolya
Sára Zsigrai
Gábor Kiszler
Géza Antalffy
Krisztina Pálóczi
Zoltán Szállási
Vanessza Szabó
Anna Sebestyén
Norbert Solymosi
Alexandra Kalmár
Kristóf Dede
Péter Lőrincz
Zsolt Tulassay
Péter Igaz
Béla Molnár


RING finger protein TOPORS modulates the expression of tumor suppressor SMAR1 in colorectal cancer via the TLR4‐TRIF pathway

Abstract: TOP1‐binding arginine/serine‐rich protein (TOPORS), a really interesting new gene finger protein, has the ability to bind to a palindromic consensus DNA sequence that enables it to function as a potential transcriptional regulator. However, its role in regulating the transcription of cancer‐associated genes is yet to be explored. As Toll‐like receptor 4 (TLR4) agonists are known to regress solid tumors, we observed that lipopolysaccharide (LPS) induces TOPORS via a TLR4‐TIR domain‐containing adapter‐inducing interferon‐β‐dependent pathway, which in turn modulates the transcription of tumor suppressor scaffold/matrix attachment region‐binding protein 1 (SMAR1, also known as BANP). ChIP analysis showed that TOPORS binds on the SMAR1 promoter and its occupancy increases upon LPS treatment. A previous study from our laboratory revealed that SMAR1 acts as a repressor of signal transducer and activator of transcription 3 (STAT3) transcription. Tumor growth, as well as tumor‐associated macrophage polarization, depends on the status of the STAT1:STAT3 ratio. LPS‐induced SMAR1 expression decreases STAT3 expression and also skews the macrophage polarization toward M1 phenotype. In contrast, LPS failed to polarize tumor‐associated macrophages to M1 phenotype in a SMAR1‐silenced condition, which shows the involvement of SMAR1 in dictating the fate of colorectal cancer progression. Identification of the molecular mechanism behind LPS‐mediated tumor regression would be crucial for designing cancer treatment strategies involving bacterial components.

Priyanka Firmal
Vibhuti Kumar Shah
Richa Pant
Samit Chattopadhyay


Relaxed Eddy Accumulation Outperforms Monin‐Obukhov Flux Models Under Non‐Ideal Conditions

Abstract: Abstract The Monin‐Obukhov Similarity Theory (MOST) links turbulent statistics to surface fluxes through universal functions. Here, we investigate its performance over a large lake, where none of its assumptions (flat homogeneous surface) are obviously violated. We probe the connection between the variance budget terms and departure from the nondimensional flux‐variance function for CO2, water vapor, and temperature. Our results indicate that both the variance storage and its vertical transport affect MOST, and these terms are most significant when small fluxes and near neutral conditions were prevalent. Such conditions are common over lakes and oceans, especially for CO2, underlining the limitation of using any MOST‐based methods to compute small fluxes. We further show that the relaxed eddy accumulation (REA) method is more robust and less sensitive to storage and transport, adequately reproducing the eddy‐covariance fluxes even for the smallest flux magnitudes. Therefore, we recommend REA over MOST methods for trace‐gas flux estimation.

Einara Zahn
Elie Bou‐Zeid
Nelson Luís Dias


The niche-derived glial cell line-derived neurotrophic factor (GDNF) induces migration of mouse spermatogonial stem/progenitor cells.

Abstract: In mammals, the biological activity of the stem/progenitor compartment sustains production of mature gametes through spermatogenesis. Spermatogonial stem cells and their progeny belong to the class of undifferentiated spermatogonia, a germ cell population found on the basal membrane of the seminiferous tubules. A large body of evidence has demonstrated that glial cell line-derived neurotrophic factor (GDNF), a Sertoli-derived factor, is essential for in vivo and in vitro stem cell self-renewal. However, the mechanisms underlying this activity are not completely understood. In this study, we show that GDNF induces dose-dependent directional migration of freshly selected undifferentiated spermatogonia, as well as germline stem cells in culture, using a Boyden chamber assay. GDNF-induced migration is dependent on the expression of the GDNF co-receptor GFRA1, as shown by migration assays performed on parental and GFRA1-transduced GC-1 spermatogonial cell lines. We found that the actin regulatory protein vasodilator-stimulated phosphoprotein (VASP) is specifically expressed in undifferentiated spermatogonia. VASP belongs to the ENA/VASP family of proteins implicated in actin-dependent processes, such as fibroblast migration, axon guidance, and cell adhesion. In intact seminiferous tubules and germline stem cell cultures, GDNF treatment up-regulates VASP in a dose-dependent fashion. These data identify a novel role for the niche-derived factor GDNF, and they suggest that GDNF may impinge on the stem/progenitor compartment, affecting the actin cytoskeleton and cell migration.

Lisa Dovere
Stefania Fera
Margherita Grasso
Dante Lamberti
Cesare Gargioli
Barbara Muciaccia
Anna Maria Lustri
Mario Stefanini
Elena Vicini


De novo transcriptome and small RNA analysis of two Chinese willow cultivars reveals stress response genes in Salix matsudana.

Abstract: Salix matsudana Koidz. is a deciduous, rapidly growing, and drought resistant tree and is one of the most widely distributed and commonly cultivated willow species in China. Currently little transcriptomic and small RNAomic data are available to reveal the genes involve in the stress resistant in S. matsudana. Here, we report the RNA-seq analysis results of both transcriptome and small RNAome data using Illumina deep sequencing of shoot tips from two willow variants(Salix. matsudana and Salix matsudana Koidz. cultivar 'Tortuosa'). De novo gene assembly was used to generate the consensus transcriptome and small RNAome, which contained 106,403 unique transcripts with an average length of 944 bp and a total length of 100.45 MB, and 166 known miRNAs representing 35 miRNA families. Comparison of transcriptomes and small RNAomes combined with quantitative real-time PCR from the two Salix libraries revealed a total of 292 different expressed genes(DEGs) and 36 different expressed miRNAs (DEMs). Among the DEGs and DEMs, 196 genes and 24 miRNAs were up regulated, 96 genes and 12 miRNA were down regulated in S. matsudana. Functional analysis of DEGs and miRNA targets showed that many genes were involved in stress resistance in S. matsudana. Our global gene expression profiling presents a comprehensive view of the transcriptome and small RNAome which provide valuable information and sequence resources for uncovering the stress response genes in S. matsudana. Moreover the transcriptome and small RNAome data provide a basis for future study of genetic resistance in Salix.

Guodong Rao
Jinkai Sui
Yanfei Zeng
Caiyun He
Aiguo Duan
Jianguo Zhang


Correction: Stage-Stratified Analysis of Prognostic Significance of Tumor Size in Patients with Gastric Cancer


Risks to birds traded for African traditional medicine: a quantitative assessment.

Abstract: Few regional or continent-wide assessments of bird use for traditional medicine have been attempted anywhere in the world. Africa has the highest known diversity of bird species used for this purpose. This study assesses the vulnerability of 354 bird species used for traditional medicine in 25 African countries, from 205 genera, 70 families, and 25 orders. The orders most represented were Passeriformes (107 species), Falconiformes (45 species), and Coraciiformes (24 species), and the families Accipitridae (37 species), Ardeidae (15 species), and Bucerotidae (12 species). The Barn owl (Tyto alba) was the most widely sold species (seven countries). The similarity of avifaunal orders traded is high (analogous to "morphospecies", and using Sørensen's index), which suggests opportunities for a common understanding of cultural factors driving demand. The highest similarity was between bird orders sold in markets of Benin vs. Burkina Faso (90%), but even bird orders sold in two geographically separated countries (Benin vs. South Africa and Nigeria vs. South Africa) were 87% and 81% similar, respectively. Rabinowitz's "7 forms of rarity" model, used to group species according to commonness or rarity, indicated that 24% of traded bird species are very common, locally abundant in several habitats, and occur over a large geographical area, but 10% are rare, occur in low numbers in specific habitats, and over a small geographical area. The order with the highest proportion of rare species was the Musophagiformes. An analysis of species mass (as a proxy for size) indicated that large and/or conspicuous species tend to be targeted by harvesters for the traditional medicine trade. Furthermore, based on cluster analyses for species groups of similar risk, vultures, hornbills, and other large avifauna, such as bustards, are most threatened by selective harvesting and should be prioritised for conservation action.

Vivienne L Williams
Anthony B Cunningham
Alan C Kemp
Robin K Bruyns


A modern mode of activation for nucleic acid enzymes.

Abstract: Through evolution, enzymes have developed subtle modes of activation in order to ensure the sufficiently high substrate specificity required by modern cellular metabolism. One of these modes is the use of a target-dependent module (i.e. a docking domain) such as those found in signalling kinases. Upon the binding of the target to a docking domain, the substrate is positioned within the catalytic site. The prodomain acts as a target-dependent module switching the kinase from an off state to an on state. As compared to the allosteric mode of activation, there is no need for the presence of a third partner. None of the ribozymes discovered to date have such a mode of activation, nor does any other known RNA. Starting from a specific on/off adaptor for the hepatitis delta virus ribozyme, that differs but has a mechanism reminiscent of this signalling kinase, we have adapted this mode of activation, using the techniques of molecular engineering, to both catalytic RNAs and DNAs exhibiting various activities. Specifically, we adapted three cleaving ribozymes (hepatitis delta virus, hammerhead and hairpin ribozymes), a cleaving 10-23 deoxyribozyme, a ligating hairpin ribozyme and an artificially selected capping ribozyme. In each case, there was a significant gain in terms of substrate specificity. Even if this mode of control is unreported for natural catalytic nucleic acids, its use needs not be limited to proteinous enzymes. We suggest that the complexity of the modern cellular metabolism might have been an important selective pressure in this evolutionary process.

Dominique Lévesque
Francis P Brière
Jean-Pierre Perreault


Both neurons and astrocytes exhibited tetrodotoxin-resistant metabotropic glutamate receptor-dependent spontaneous slow Ca2+ oscillations in striatum.

Abstract: The striatum plays an important role in linking cortical activity to basal ganglia outputs. Group I metabotropic glutamate receptors (mGluRs) are densely expressed in the medium spiny projection neurons and may be a therapeutic target for Parkinson's disease. The group I mGluRs are known to modulate the intracellular Ca(2+) signaling. To characterize Ca(2+) signaling in striatal cells, spontaneous cytoplasmic Ca(2+) transients were examined in acute slice preparations from transgenic mice expressing green fluorescent protein (GFP) in the astrocytes. In both the GFP-negative cells (putative-neurons) and astrocytes of the striatum, spontaneous slow and long-lasting intracellular Ca(2+) transients (referred to as slow Ca(2+) oscillations), which lasted up to approximately 200 s, were found. Neither the inhibition of action potentials nor ionotropic glutamate receptors blocked the slow Ca(2+) oscillation. Depletion of the intracellular Ca(2+) store and the blockade of inositol 1,4,5-trisphosphate receptors greatly reduced the transient rate of the slow Ca(2+) oscillation, and the application of an antagonist against mGluR5 also blocked the slow Ca(2+) oscillation in both putative-neurons and astrocytes. Thus, the mGluR5-inositol 1,4,5-trisphosphate signal cascade is the primary contributor to the slow Ca(2+) oscillation in both putative-neurons and astrocytes. The slow Ca(2+) oscillation features multicellular synchrony, and both putative-neurons and astrocytes participate in the synchronous activity. Therefore, the mGluR5-dependent slow Ca(2+) oscillation may involve in the neuron-glia interaction in the striatum.

Atsushi Tamura
Naohiro Yamada
Yuichi Yaguchi
Yoshio Machida
Issei Mori
Makoto Osanai


Role of PAF receptor in proinflammatory cytokine expression in the dorsal root ganglion and tactile allodynia in a rodent model of neuropathic pain.

Abstract: BACKGROUND: Neuropathic pain is a highly debilitating chronic pain following damage to peripheral sensory neurons and is often resistant to all treatments currently available, including opioids. We have previously shown that peripheral nerve injury induces activation of cytosolic phospholipase A(2) (cPLA(2)) in injured dorsal root ganglion (DRG) neurons that contribute to tactile allodynia, a hallmark of neuropathic pain. However, lipid mediators downstream of cPLA(2) activation to produce tactile allodynia remain to be determined. PRINCIPAL FINDINGS: Here we provide evidence that platelet-activating factor (PAF) is a potential candidate. Pharmacological blockade of PAF receptors (PAFRs) reduced the development and expression of tactile allodynia following nerve injury. The expression of PAFR mRNA was increased in the DRG ipsilateral to nerve injury, which was seen mainly in macrophages. Furthermore, mice lacking PAFRs showed a reduction of nerve injury-induced tactile allodynia and, interestingly, a marked suppression of upregulation of tumor necrosis factor alpha (TNFalpha) and interleukin-1beta (IL-1beta) expression in the injured DRG, crucial proinflammatory cytokines involved in pain hypersensitivity. Conversely, a single injection of PAF near the DRG of naïve rats caused a decrease in the paw withdrawal threshold to mechanical stimulation in a dose-dependent manner and an increase in the expression of mRNAs for TNFalpha and IL-1beta, both of which were inhibited by pretreatment with a PAFR antagonist. CONCLUSIONS: Our results indicate that the PAF/PAFR system has an important role in production of TNFalpha and IL-1beta in the DRG and tactile allodynia following peripheral nerve injury and suggest that blocking PAFRs may be a viable therapeutic strategy for treating neuropathic pain.

Shigeo Hasegawa
Yuta Kohro
Miho Shiratori
Satoshi Ishii
Takao Shimizu
Makoto Tsuda
Kazuhide Inoue


Altered expression of cyclin A 1 in muscle of patients with facioscapulohumeral muscle dystrophy (FSHD-1).

Abstract:
Objectives
Cyclin A1 regulates cell cycle activity and proliferation in somatic and germ-line cells. Its expression increases in G1/S phase and reaches a maximum in G2 and M phases. Altered cyclin A1 expression might contribute to clinical symptoms in facioscapulohumeral muscular dystrophy (FSHD).
Methods
Muscle biopsies were taken from the Vastus lateralis muscle for cDNA microarray, RT-PCR, immunohistochemistry and Western blot analyses to assess RNA and protein expression of cyclin A1 in human muscle cell lines and muscle tissue. Muscle fibers diameter was calculated on cryosections to test for hypertrophy.
Results
cDNA microarray data showed specifically elevated cyclin A1 levels in FSHD vs. other muscular disorders such as caveolinopathy, dysferlinopathy, four and a half LIM domains protein 1 deficiency and healthy controls. Data could be confirmed with RT-PCR and Western blot analysis showing up-regulated cyclin A1 levels also at protein level. We found also clear signs of hypertrophy within the Vastus lateralis muscle in FSHD-1 patients.
Conclusions
In most somatic human cell lines, cyclin A1 levels are low. Overexpression of cyclin A1 in FSHD indicates cell cycle dysregulation in FSHD and might contribute to clinical symptoms of this disease.

Anna Pakula
Joanna Schneider
Jürgen Janke
Ute Zacharias
Herbert Schulz
Norbert Hübner
Anja Mähler
Andreas Spuler
Simone Spuler
Pierre Carlier
Michael Boschmann


Elimination of self-reactive T cells in the thymus: a timeline for negative selection.

Abstract: The elimination of autoreactive T cells occurs via thymocyte apoptosis and removal by thymic phagocytes, but the sequence of events in vivo, and the relationship between thymocyte death and phagocytic clearance, are unknown. Here we address these questions by following a synchronized cohort of thymocytes undergoing negative selection within a three-dimensional thymic tissue environment, from the initial encounter with a negative selecting ligand to thymocyte death and clearance. Encounter with cognate peptide-MHC complexes results in rapid calcium flux and migratory arrest in auto-reactive thymocytes over a broad range of peptide concentrations, followed by a lag period in which gene expression changes occurred, but there was little sign of thymocyte death. Caspase 3 activation and thymocyte loss were first detectable at 2 and 3 hours, respectively, and entry of individual thymocytes into the death program occurred asynchronously over the next 10 hours. Two-photon time-lapse imaging revealed that thymocyte death and phagocytosis occurred simultaneously, often with thymocytes engulfed prior to changes in chromatin and membrane permeability. Our data provide a timeline for negative selection and reveal close coupling between cell death and clearance in the thymus.

Ivan Lilyanov Dzhagalov
Katherine Grace Chen
Paul Herzmark
Ellen A Robey


Prognostic accuracy of the CMPMIT-ICD-10, APACHE Ⅱ, SOFA, ISS, and AIS for in-hospital death among patients with traumatic hemorrhagic shock.

Abstract: The China Mortality Prediction Model in Trauma, which is based on the International Classification of Disease Disorders (ICD)-10-CM lexicon (CMPMIT-ICD-10),is a new trauma scoring system. Our objective was to compare the prognostic performance of the CMPMIT-ICD10 with that of the Acute Physiology and Chronic Health Evaluation II (APACHEII), Sequential Organ Failure Assessment (SOFA), Injury Severity Score (ISS), and Abbreviated Injury Scale (AIS) for in-hospital mortality in patients with traumatic hemorrhagic shock(THS).This retrospective observational cohort study was conducted at a tertiary teaching hospital from May 1, 2013, to May 31, 2023.The area under the receiver operating characteristic curve (AUC), sensitivity, specificity, accuracy, and associations with outcomes of theCMPMIT-ICD-10, APACHE II, SOFA, ISS, and AIS scores for the prediction of in-hospital death were assessed. A total of 420 patients with THS were included. Forty-one (9.8%) patients died during hospitalization. For the prediction of in-hospital death, the CMPMIT-ICD-10 (0.8757) and APACHE II(0.8709) had greater AUCs compared with the AIS (0.6243), SOFA (0.7669), and ISS (0.6601). With the best cut-off value of 59.5, the CMPMIT-ICD10 had a highest sensitivity (85.4%) and good specificity(79.9%) and overall accuracy (80.4%). The CMPMIT-ICD10 (OR 1.057, 95% CI 1.028-1.087, p < 0.001) and APACHE II (OR 1.125, 95% CI 1.045-1.211, p = 0.002) were independently associated with in-hospital death. Comparable to the APACHE II but significantly better than the SOFA, ISS, and AIS, the CMPMIT-ICD-10 performed well in predicting the short-term mortality of patients with THS. These findings suggest that the CMPMIT-ICD-10 may have superior utility for predicting short-term death in THS patients.

Jie Cai
Gang Zhou
Feifei Jin
Haiyan Xue
Shu Li
Chun Fu
Zhenzhou Wang
Wei Huang
Tianbing Wang
Fengxue Zhu
Xiujuan Zhao


Viral piracy of host RNA phosphatase DUSP11 by avipoxviruses.

Abstract: Proper recognition of viral pathogens is an essential part of the innate immune response. A common viral replicative intermediate and chemical signal that cells use to identify pathogens is the presence of a triphosphorylated 5' end (5'ppp) RNA, which activates the cytosolic RNA sensor RIG-I and initiates downstream antiviral signaling. While 5'pppRNA generated by viral RNA-dependent RNA polymerases (RdRps) can be a potent activator of the immune response, endogenous RNA polymerase III (RNAPIII) transcripts can retain the 5'ppp generated during transcription and induce a RIG-I-mediated immune response. We have previously shown that host RNA triphosphatase dual-specificity phosphatase 11 (DUSP11) can act on both host and viral RNAs, altering their levels and reducing their ability to induce RIG-I activation. Our previous work explored how experimentally altered DUSP11 activity can impact immune activation, prompting further exploration into natural contexts of altered DUSP11 activity. Here, we have identified viral DUSP11 homologs (vDUSP11s) present in some avipoxviruses. Consistent with the known functions of host DUSP11, we have shown that expression of vDUSP11s: 1) reduces levels of endogenous RNAPIII transcripts, 2) reduces a cell's sensitivity to 5'pppRNA-mediated immune activation, and 3) restores virus infection defects seen in the absence of DUSP11. Our results identify a context where DUSP11 activity has been co-opted by viruses to alter RNA metabolism and influence the outcome of infection.

Kayla H Szymanik
Emily A Rex
Vamshikrishna R Pothireddy
Don B Gammon
Dustin C Hancks
Christopher S Sullivan

Immunologic diseases. Allergy
Biology (General)


Decision rules and group rationality: cognitive gain or standstill?

Abstract: Recent research in group cognition points towards the existence of collective cognitive competencies that transcend individual group members' cognitive competencies. Since rationality is a key cognitive competence for group decision making, and group cognition emerges from the coordination of individual cognition during social interactions, this study tests the extent to which collaborative and consultative decision rules impact the emergence of group rationality. Using a set of decision tasks adapted from the heuristics and biases literature, we evaluate rationality as the extent to which individual choices are aligned with a normative ideal. We further operationalize group rationality as cognitive synergy (the extent to which collective rationality exceeds average or best individual rationality in the group), and we test the effect of collaborative and consultative decision rules in a sample of 176 groups. Our results show that the collaborative decision rule has superior synergic effects as compared to the consultative decision rule. The ninety one groups working in a collaborative fashion made more rational choices (above and beyond the average rationality of their members) than the eighty five groups working in a consultative fashion. Moreover, the groups using a collaborative decision rule were closer to the rationality of their best member than groups using consultative decision rules. Nevertheless, on average groups did not outperformed their best member. Therefore, our results reveal how decision rules prescribing interpersonal interactions impact on the emergence of collective cognitive competencies. They also open potential venues for further research on the emergence of collective rationality in human decision-making groups.

Petru Lucian Curşeu
Rob J G Jansen
Maryse M H Chappin


Correction: Postnatal Environmental Tobacco Smoke Exposure Related to Behavioral Problems in Children.

Abstract: [This corrects the article DOI: 10.1371/journal.pone.0133604.].

Julie Chastang
Nour Baïz
Jean Sébastien Cadwallader
Sarah Robert
John L Dywer
Denis André Charpin
Denis Caillaud
Frédéric de Blay
Chantal Raherison
François Lavaud
Isabella Annesi-Maesano