Loss of ATP-Dependent Citrate Lyase Drives Left Ventricular Dysfunction by Metabolic Remodeling

Abstract: Metabolic adaptation and maladaptation are hallmarks of the failing heart and may be a target for therapeutic interventions. For example, sustained glucose oxidation during cardiac stress is associated with increased activity and abundance of ACL (ATP-dependent citrate lyase, Acly), which produces acetyl-coenzyme A (CoA) from citrate and CoA and supports de novo lipid synthesis. However, our understanding of how ACL supports cardiac metabolic adaptation and its potential to modulate disease pathophysiology has not yet been investigated. We used human heart tissue samples from healthy donors and patients with nonischemic cardiomyopathy. Next, we used CRISPR (clustered, regularly interspaced short palindromic repeats)/Cas9 (CRISPR-associated 9) gene editing to inactivate Acly in cardiomyocytes of Myh6-Cas9 mice. In vivo positron emission tomography and ex vivo stable isotope tracer labeling were used to quantify metabolic flux changes in response to Acly knockdown. We conducted a multi-omics analysis using RNA sequencing and mass spectrometry-based metabolomics and proteomics. Experimental data were integrated into computational modeling using the metabolic network CardioNet to identify significantly dysregulated metabolic processes at a systems level. We observed reduced ACL abundance and activity in human heart tissue samples from patients with nonischemic cardiomyopathy, which correlated with decreased abundance of Krebs cycle intermediates. Using CRISPR/Cas9 gene editing, we found that cardiac-specific loss of ACL reduces acetyl-CoA synthesis, leading to altered cardiac metabolism characterized by increased glucose uptake and oxidation, impaired energy flux, and elevated AMP to ATP ratios, which collectively promote left ventricular dysfunction. Transcriptomic and mass spectrometry-based metabolomics, as well as proteomic data, reveal compensatory cardiac lipid remodeling and reduced histone 3 acetylation. This metabolic stress promotes activation of AMPK (AMP kinase) and PKA (protein kinase A), which in turn mediates YAP (Yes-associated protein) inhibition through phosphorylation. Stable isotope tracer studies combined with CardioNet simulations demonstrated that increased IDH1 (isocitrate dehydrogenase 1) activity prevents allosteric inhibition of glycolysis from cytosolic citrate accumulation. AAV9-mediated cardiac Idh1 deletion improved cardiac function and energy provision, reducing YAP phosphorylation and restoring downstream YAP signaling. Our findings suggest that ACL plays a pivotal role in cardiac metabolism through regulating lipid synthesis and cardiac function. Exploiting compensatory pathways of citrate metabolism may improve cardiac function during heart failure.

Liu S
Gammon ST
Tan L
Gao Y
Kim K
Elbatreek MH
Arrieta A
Williamson IK
Salazar RL
Pham J
Davidian A
Khanna Neicheril R
Gould BD
Vitrac H
Sadiq A
Dinh AQ
Lien EC
de Luna Vitorino FN
Gongora JM
Martinez SA
Odenkirk MT
Boatman AK
Chappel JR
Czer LSC
Kransdorf EP
Lefer DJ
Hanson BM
Garcia BA
Baker EM
Vander Heiden MG
Lorenzi PL
Taegtmeyer H
Piwnica-Worms D
Martin JF
Karlstaedt A

Humans
ATP Citrate (pro-S)-Lyase
Animals
Ventricular Dysfunction, Left
Mice
Myocytes, Cardiac
Male
Female
Cardiomyopathies
Energy Metabolism


Caffeine and Cardiovascular Disease: A Scientific Statement From the American Heart Association

Abstract: Caffeine is one of the most commonly consumed drugs in the world. It is found in various naturally occurring substances and can be ingested in a synthetically derived pure form. The majority of human subject-based research is observational and has focused on beverages and foods that contain caffeine. The relationships between caffeine and cardiovascular risk factors and diseases are complex, exhibiting heterogeneity depending on the nature of the caffeine consumed and individual-level propensities. Acute versus chronic caffeine-associated cardiovascular effects are often different. Most studies suggest an inverse J-shaped relationship between consumption of naturally occurring caffeinated products and blood pressure. Data on relationships between caffeine and diabetes are not consistent, but habitual coffee consumption has been associated with a lower risk of incident type 2 diabetes. Whereas no clear relationship between caffeine and blood lipids is evident, unfiltered coffee raises low-density lipoprotein cholesterol. Caffeine, studied primarily in the context of coffee, has been shown either to have no relationship or to be associated with a lower risk of coronary artery disease and heart failure. Randomized controlled trial data among regular caffeinated coffee drinkers showed that caffeinated coffee decreases the risk of atrial fibrillation occurrence but increases the frequency of premature ventricular contractions. Data are fairly consistent that moderate caffeine consumption, again studied primarily in the setting of coffee consumption, was associated with a lower risk of stroke. Data on high doses of caffeine such as that found in energy drinks are limited and generally suggest cardiovascular harm.

American Heart Association Council on Lifestyle and Cardiometabolic Health; Council on Clinical Cardiology; and Stroke Council


Correction to: 2026 AHA/ACC/ACCP/ACEP/CHEST/SCAI/ SHM/SIR/SVM/SVN Guideline for the Evaluation and Management of Acute Pulmonary Embolism in Adults: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines

Creager MA
Barnes GD
Giri J
Mukherjee D
Jones WS
Burnett AE
Carman T
Casanegra AI
Castellucci LA
Clark SM
Cushman M
de Wit K
Eaves JM
Fang MC
Goldberg JB
Henkin S
Johnston-Cox H
Kadavath S
Kadian-Dodov D
Keeling WB
Klein AJP
Li J
McDaniel MC
Moores LK
Piazza G
Prenger KS
Pugliese SC
Ranade M
Rosovsky RP
Russo F
Secemsky EA
Sista AK
Tefera L
Weinberg I
Westafer LM
Young MN


Transforming Pulmonary Arterial Hypertension: Key Milestones and Future Perspectives

Abstract: Pulmonary arterial hypertension (PAH) is a rare, progressive disease of the precapillary pulmonary arteries, characterized by fibroproliferative vascular remodeling, increased pulmonary vascular resistance, right ventricular failure, and premature death. Over the past four decades, substantial advances in understanding PAH pathobiology, epidemiology, diagnosis, and treatment have meaningfully improved patient outcomes. The pathobiology of PAH is multifaceted, involving endothelial dysfunction, smooth muscle cell hyperproliferation, inflammation, and dysregulation of key signaling pathways, including the prostacyclin, nitric oxide, endothelin 1, and bone morphogenetic/TGF-β (transforming growth factor β) axes. Dysregulation of the activin arm of the TGF-β pathway has emerged as a critical driver of vascular remodeling and is the target of sotatercept, the first antiremodeling therapy approved for PAH. Epidemiologically, PAH now more commonly affects older adults with cardiovascular and pulmonary comorbidities compared with historical cohorts. The global burden varies considerably, with methamphetamine-associated PAH rising in North America and schistosomiasis- and HIV-associated PAH prevalent in low- and middle-income countries, where underdiagnosis likely remains substantial. Diagnosis continues to be delayed, with advanced symptoms present at the time of diagnosis for most patients. Right heart catheterization remains essential for definitive diagnosis. Emerging tools, including artificial intelligence applied to electrocardiography, echocardiography, and electronic health records, hold promise for earlier case identification. Management and prognostication of PAH is based on regular risk stratification using validated multiparameter tools. The initial therapy choice is up-front combination therapy with 2 oral medications for most patients, with initial triple therapy that includes a parenteral prostacyclin used in high-risk patients. Add-on therapy with sotatercept is now an option for patients not achieving low risk, a strategy that led to improvements in hemodynamics, right heart function, and reduced the risk of adverse clinical outcomes in recent randomized trials. For patients who remain at higher risk despite maximal therapy, lung transplantation remains an important and life-saving option. Despite remarkable therapy progress, gaps persist in earlier detection, management of comorbid phenotypes, personalized therapy, and novel therapies targeting right ventricular failure. Ongoing clinical trials and translational research continue to advance the field toward the goal of normal survival and quality of life for patients with PAH.

Humans
Pulmonary Arterial Hypertension
Animals
Vascular Remodeling
Antihypertensive Agents
Hypertension, Pulmonary


Reversible ECG Changes in a Rare Case of Shock


Letter by Astan et al Regarding Article, "The Role of the Collateral Circulation in Stable Angina: An Invasive Placebo-Controlled Study"


An Integrated Ecosystem for Cardiovascular Science and Health


Response by Gentile et al to Letters Regarding Article, "Clinical and Prognostic Significance of Anomalous Origin of a Coronary Artery in Adults"


Letter by Han et al Regarding Article, "Clinical and Prognostic Significance of Anomalous Origin of a Coronary Artery in Adults"

Han QJ
Stefanescu Schmidt AC
DeFaria Yeh D


Letter by Li and Zhang Regarding Article, "Clinical and Prognostic Significance of Anomalous Origin of a Coronary Artery in Adults"


Recurrent Venous Thromboembolism in Cancer: A Foreboding Event


Prognosis of Recurrent Venous Thromboembolism During Extended Apixaban Therapy for Cancer-Associated Thrombosis: Insights From the API-CAT Randomized Trial

Mahé I
Chapelle C
Righini M
Le Gal G
Klok FA
Agnelli G
Cajfinger F
Sevestre MA
Grenier PA
Alexandre J
Couturaud F
Mismetti P
Laporte S
Chidiac J


Scaled Multidimensional Assays of Variant Effect Identify Sequence-Function Relationships in Hypertrophic Cardiomyopathy

Abstract: An estimated 1 in 500 people lives with hypertrophic cardiomyopathy (HCM), a disease for which genetic diagnosis can identify family members at risk and increasingly guide therapy. Variants in the MYBPC3 gene, which encodes cardiac myosin-binding protein C (cMyBP-C), account for a significant proportion of HCM cases. However, many of these are classified as variants of uncertain significance, complicating clinical decision-making. Scalable methods for variant interpretation in disease-specific cell types are crucial for understanding variant impact and uncovering disease mechanisms. We developed a scaled multidimensional mapping strategy to evaluate the functional impact of variants across a critical domain of cMyBP-C. We incorporate saturation base editing at the native MYBPC3 locus, a long-read RNA sequencing-enabled assay of variant splice effects, and measurements of HCM-relevant phenotypes, including cMyBP-C abundance, hypertrophic signaling, and ubiquitin-proteasome function in human induced pluripotent stem cell-derived cardiomyocytes. Our multidimensional mapping strategy enabled high-resolution functional analysis of MYBPC3 variants in induced pluripotent stem cell-derived cardiomyocytes. Our massively parallel splicing assay identified novel splice-disrupting variants. Targeted transient base editing generated a comprehensive variant library at the native locus, capturing diverse variant effects on cellular HCM-relevant phenotypes. Integration of functional assays revealed that decreased cMyBP-C abundance is a key driver of HCM-related phenotypes. In parallel, downregulation of protein degradation was observed to correlate with MYBPC3 loss of function, and novel potential disease mechanisms were identified for missense variants near a critical binding domain. Bayesian estimates of variant effects enable the reclassification of clinical variants. This work provides a platform for extending genome engineering in induced pluripotent stem cells to multiplexed assays of variant effects across diverse disease-relevant cellular phenotypes, enhancing our understanding of variant pathogenicity and uncovering novel biological mechanisms that could inform therapeutic strategies.

Yamamoto Y
Chua K
Staudt D
Ferrasse A
Kirillova A
De Jong HN
Floyd BJ
Cadisch C
Wiel L
Wang Q
O'Neill MJ
Tabet D
Goryznski JE
Huang Y
Bai F
Wilson RH
Sharma A
Tapales A
Agrawal R
Wheeler MT
Mercola M
MacRae CA
Roden DM
Roth FP
Glazer AM
Ashley EA
Parikh VN


Exercise Training in High-Risk Populations: A Scientific Statement From the American Heart Association

Abstract: There is broad consensus on the benefits of aerobic exercise training in patients with cardiovascular disease to improve cardiorespiratory fitness and lower the risk of adverse cardiovascular events. However, certain high-risk populations such as those with frailty, stroke, spinal cord injury, rheumatological conditions, or genetic cardiomyopathies and recipients of advanced heart failure therapies or cardiac implantable electronic devices warrant special considerations with regard to exercise training. This scientific statement summarizes the present state and future directions of exercise training for these high-risk populations, including functional deficits, responses to exercise training, modifications in training programs required to maximize safety and efficacy, and knowledge gaps in this field. Key findings common across most of these high-risk populations include (1) increased barriers to participation in exercise training at multiple levels; (2) low baseline cardiorespiratory fitness, creating heightened need for exercise interventions; (3) modifications to exercise prescription, frequently emphasizing strength, balance, and flexibility in addition to aerobic training, as well as accommodations with enhanced supervision and specialized equipment as needed; and (4) functional and quality-of-life gains in response to appropriately designed exercise programs that match or exceed those in more traditional populations. Future research is needed to further develop patient-centered training regimens designed to address the unique and heterogeneous needs of these populations, evaluate their impact on clinical and patient-centered outcomes, and advance scalable and equitable delivery of exercise therapies proven safe and effective.

American Heart Association Exercise, Cardiac Rehabilitation, and Sports Cardiology Science Committee of the Council on Clinical Cardiology; Council on Cardiovascular and Stroke Nursing; Council on Cardiovascular Surgery and Anesthesia; Council on Lifelong Congenital Heart Disease and Heart Health in the Young; Council on Quality of Care and Outcomes Research; and Stroke Council


Cardiovascular Health Equity: Time for a New Era of Science, Sociology, and Interventions

Itchhaporia D
Yancy CW
Rosen SE
Mbakwem AC
Münzel T
Timmis A
Kramer C


Deprescribing in Patients With Cardiovascular Disease Experiencing Polypharmacy: A Scientific Statement From the American Heart Association

Abstract: Polypharmacy in patients with cardiovascular disease occurs frequently across the age spectrum and can lead to inappropriate prescribing and adverse outcomes. Despite polypharmacy being a known problem for decades, there is limited guidance describing how to manage polypharmacy in patients with cardiovascular disease, including when and how to initiate deprescribing strategies. Although polypharmacy can occur at any age, studies often focus on older adults. The prevalence and consequences of polypharmacy, coupled with current gaps in the deprescribing literature, highlight the need for a scientific statement focused on deprescribing in all patients with cardiovascular disease. Deprescribing can improve outcomes and can apply to both cardiovascular and noncardiovascular drugs because both contribute to polypharmacy and poor outcomes associated with inappropriate prescribing in patients with cardiovascular disease. This scientific statement reviews the consequences of polypharmacy in patients with cardiovascular disease and provides tailored deprescribing strategies across the life span, with an emphasis on the unique considerations in pediatric, adult, and older adult populations. These strategies include observing clinical cues and triggers, using validated deprescribing tools, engaging in shared decision-making, and leveraging the roles of all members of the health care team to address barriers to deprescribing. Last, this scientific statement highlights current challenges related to polypharmacy and deprescribing and suggests some strategies to address them.

American Heart Association Clinical Pharmacology Committee of the Council on Clinical Cardiology; Council on Cardiovascular and Stroke Nursing; Council on Cardiovascular Surgery and Anesthesia; and Council on Quality of Care and Outcomes Research


A Bundle to Frame Guidelines and American Heart Association Statements


A New Circulation, For You


Cardiovascular Risk Reduction With GLP-1 RA Drugs

Abstract: GLP-1 (glucagon-like peptide-1) receptor agonists (RAs) have emerged as a major therapeutic advance in cardiometabolic medicine. Initially developed as glucose-lowering therapies for type 2 diabetes, these agents have demonstrated broad benefits that extend well beyond glycemic control. GLP-1 RAs enhance glucose-dependent insulin secretion and reduce appetite, leading to improved glycemia and sustained weight loss. In addition, GLP-1 signaling exerts vascular and myocardial effects, including improved endothelial function, reduced inflammation and oxidative stress, and favorable changes in cardiac metabolism and remodeling. Large randomized cardiovascular outcomes trials have consistently shown that several GLP-1 RAs reduce major adverse cardiovascular events, including myocardial infarction, stroke, cardiovascular death, and heart failure. Benefits have been observed across diverse populations, including individuals with established cardiovascular disease and those with obesity but without diabetes. Emerging therapies targeting multiple incretin pathways, such as dual GIP (glucose-dependent insulinotropic polypeptide)-GLP-1 RAs, may further extend these benefits. Collectively, these findings suggest that GLP-1 RAs influence multiple cardiometabolic pathways and may shift the underlying metabolic milieu toward a more favorable physiological state. In this Clinical Primer, we review the physiology of GLP-1 signaling, the evidence supporting cardiovascular risk reduction, and practical considerations for the clinical use of incretin-based therapies.

Glucagon-Like Peptide-1 Receptor Agonists


Obesity, Severe Obesity, and Abdominal Obesity in US Youth and Adults From 1999 to 2023

Minhas AS
Wallace AS
Zhang S
Barrett RB
Ndumele CE


Association of body roundness index with stroke and mortality among people with normal body mass index

Abstract: The Body Roundness Index (BRI) is a novel anthropometric measure that can predict total and regional body fat percentages. However, the effects of BRI in individuals with a normal Body Mass Index (BMI) remain unclear. This study aimed to investigate the association of BRI with stroke and all-cause mortality in individuals with a normal BMI. This longitudinal study included 36,490 participants free from cardiovascular diseases (CVD) and possessed a normal BMI (18.5-24.0) at baseline. Cox proportional hazard models were used to estimate the associations between BRI and the risk of stroke and all-cause mortality. Receiver operating characteristic (ROC) curves were used to assess the ability of BRI to predict stroke and all-cause mortality than other anthropometric indices. During a median follow-up of 15.0 years, there were 2281 (6.3 %) recorded strokes and 5094 (14.0 %) deaths. After adjusting for potential risk factors, BRI was found to be significantly associated with increased risks of stroke (P for trend = 0.002) and mortality (P for trend <0.001), independent of BMI. The association was primarily linked to ischemic stroke (P for trend = 0.002) rather than hemorrhagic stroke. Additionally, the ROC curves indicated that BRI has better predictive power than BMI for stroke and all-cause mortality (P < 0.05). In participants with a normal BMI, higher levels of BRI were significantly associated with an increased risk of stroke and all-cause mortality. However, these findings may not generalize to women or more diverse populations, as the study mostly included men from a single occupation.

Shen Y
Tian R
Xia X
Chen S
Tian X
Wu S
Wang A

Humans
Male
Stroke
Body Mass Index
Female
Follow-Up Studies
Risk Factors
Longitudinal Studies
Prognosis
Middle Aged
ROC Curve
Adult
Aged


Spatial analysis of environmental and socioeconomic factors impacting maternal and infant health outcomes in North Carolina

Abstract: Environmental stressors like high temperatures and pollution, often compounded by socioeconomic factors, have been linked to adverse maternal and birth outcomes. Despite this well-established link, limited studies have examined the spatial relationship between these factors to prioritize community interventions and future research needs. This study examines the spatial trends linking environmental parameters, socioeconomic factors, and adverse maternal and infant health outcomes in North Carolina from 2011 to 2019. Through exploratory spatial data analysis methods, including bivariate Local Indicators of Spatial Association (LISA) and spatial regression, clusters of environmental risks and health outcomes were identified, shedding light on the disproportionate impact of structural racism and income inequality on adverse health outcomes. In addition, this analysis highlights a significant association between hazardous pollutants, as indicated by Risk-Screening Environmental Indicator (RSEI) toxicity-weighted concentrations, and adverse health outcomes, persisting even after adjusting for racial and income segregation. In contrast, heatwaves, defined as any heatwave event across the pregnancy period, showed varied effects and little significance with birth and maternal outcomes. These findings underscore the critical need for targeted interventions addressing socioeconomic disparities and environmental health hazards to enhance maternal and infant health outcomes in North Carolina and similar regions. The online version contains supplementary material available at 10.1007/s13412-025-01060-1.

Journal of environmental studies and sciences

Ulrich SE
Sugg MM
Runkle JD
Fehlman CA
Guignet D


Affirming Care Beyond Hormones: Supporting Transgender Youth in the Face of Restrictive Policies

Akgül S
Aslan C
Başar K
Nalbant K
Oğuz SH
Pehlivantürk Kızılkan M
Tüzün Z
Özon A


Staphylococcal Septic Arthritis Following Influenza A Infection

Khalilova F
Yiğit MH
Günerbüyük C
Aktürk H


Revealing BCKDK Deficiency Under Autism: A Case Report, Therapeutic Outcomes, and Literature Review

Babazade H
Günal B
Çalişgan K
Uygur E
Durcan G
Kılıç H
Zubarioglu T
Cansever MŞ
Aktuğlu-Zeybek Ç
Kiykim E


Is the Urban-Rural Divide Affectively Polarised? Comparative Evidence from Nine European Countries

Abstract: Recent studies in the United States and Europe have documented a growing divergence in voting behaviour and political attitudes between cities and the countryside. However, we still lack systematic evidence on the extent to which this urban-rural divide is also affectively polarised. To shed light on this, we advance the concept of place-based affective polarisation, which we define as the difference between in-group and out-group affect in relation to place-based groups. Drawing on original survey data from nine European countries, we show that place-based affective polarisation is substantial along the urban-rural divide and associated with strong feelings of place-based resentment and identity. Furthermore, we find that higher levels of place-based affective polarisation correlate with support for GAL parties (green, alternative, libertarian) among urbanites and support for TAN parties (traditional, authoritarian, nationalist) among ruralites. Overall, our findings point to a strong political cleavage between urban and rural areas in several European countries.


Commoning, heterotopia, and transformation: An analytical framework for and from contested spaces

Abstract: Commoning occurs when people recognize that they share something and develop a sense of mutuality toward each other along with a shared responsibility for whatever they share. Because sharing and mutuality contrast with the individualism, competitiveness, and profit orientation of contemporary capitalist societies, commoning is widely heralded for its transformative potential. Nonetheless, commoning is not inherently transformative. We argue that whether commoning supports transformation depends on its relationship with heterotopic processes. Both commoning and heterotopia-ideal typical "other" spaces characterized by looseness and denormalization-present alternatives to hegemonic norms, especially those of state-centricity, hierarchical social organization, and the prioritization of market relationships and economic growth, but they are distinct processes that do not necessarily coincide. We propose an analytical framework to guide analysis of the relationship between commoning and heterotopia and illustrate it with examples from contested urban green spaces in Liège (Belgium), Montréal (Canada), and Brussels (Belgium).

Environment and planning. D, Society & space


Enacting responsible leadership in cross-sector partnerships: A dynamic choreography of power

Abstract: How can leaders guide diverse organizations to work together on society's biggest challenges when power is unevenly distributed? Cross-sector partnerships (CSPs) bring together companies, governments, and nongovernmental organizations (NGOs) to address complex problems, yet their success hinges on how leaders navigate competing interests and shifting power dynamics. This study examines a high-profile CSP involving a Fortune 500 company, two international development organizations, and an NGO. Drawing on Mary Parker Follett's ideas about "power-with" and "power-over," I show how NGO leaders combined collaborative and more coercive tactics to move the partnership forward. My analysis reveals that responsible leadership (RL) in CSPs is not a static trait or style but evolves through a dynamic choreography of power as challenges and priorities change. The findings offer practical lessons for leaders seeking to balance ethics, inclusion, and influence in multi-stakeholder collaborations, and they extend theory by reframing RL as a shifting, context-sensitive process rather than a fixed style.

Human relations; studies towards the integration of the social sciences


Zero-Sum Thinking and the Cultural Threat of Muslim Religious Rights

Abstract: Cultural threat is one of the main explanations for opposing immigrants. However, it lacks theoretical precision and suffers from measurement issues. To remedy these problems, we conceptualize cultural threat as a zero-sum problem and specify concrete cultural rights that Muslims receive. In two online experiments in Germany, we randomly assigned people to situations where Muslim cultural rights either replace majority rights (zero-sum) or they co-exist (non-zero-sum). The willingness to accommodate Muslims' cultural rights varies strongly by the logic of cultural threat, especially for respondents with an inclusionary mindset. They are protective of their own cultural practices, but do not perceive all gains in Muslim rights as inherently threatening. Respondents with an exclusionary mindset, however, respond less to variations in cultural threat. In contrast to people with an inclusionary mindset, they also react more negatively to Muslim than non-Muslim demands for change.


Platform-mediated racialization: A case study of rural Chinese wig sellers and Black clients on Alibaba

Abstract: Due to the rise of global e-commerce platforms like Alibaba, online interactions between rural Chinese wig sellers and Black clients are increasing. However, the racial implications of such platform-mediated business relations remain underexplored. Based on ethnographic fieldwork in Xuchang, a leading distribution and export center for wigs products in the global supply chain, this research examines the active role of Alibaba in orchestrating, structuring, and shaping the racial knowledge formation of rural Chinese wig sellers in their daily online interactions with Black clients. We argue that the exploitative nature of platform capitalism creates stress and exhaustion among rural wig sellers and pushes them to draw narrow and hasty conclusions about Blackness that dovetail with racialized hierarchy in the global wig industry and logistics networks. This research bridges the gap between platform studies and critical race studies and contributes to the reconceptualization of relations between platform and race.


Mass Mobilization in the Modern Era: Introducing the Opposition Movements and Groups (OMG) Dataset, 1789-2019

Abstract: The nature and consequences of mass mobilization are core topics in the social sciences. How have mass mobilization movements evolved over time? How do key characteristics of such movements, including their social composition or ideology, influence their ability to overthrow or alter political institutions? We introduce the Opposition Movements and Groups (OMG) dataset, which - due to its unique contents and extensive coverage - will help researchers to better address these and many other questions about mass mobilization movements. OMG includes information on the stated goals, duration, size, tactics, ideology, and social and organizational composition of 1452 mass mobilization movements, globally, from 1789 to 2019. We discuss OMG's contents, construction, validity and reliability issues, and how it complements existing datasets. We showcase the data, first, by documenting several key trends in movement characteristics since the French Revolution, and, second, by shedding new light on the much-discussed relationship between nonviolent movements and democratization.

Dahl M
Dahlum S
Fjelde H
Gjerløw H
Knutsen CH
Strøm-Sedgwick C
Wig T


From cruel optimism to foreclosed futures: The emotional and temporal dimensions of enduring precarity among young adults in Barcelona

Abstract: This paper contributes to geographical research on precarity by exploring how emotional responses to enduring insecurity shape young people's temporal horizons, spatial belonging, and sense of possibility. Drawing on qualitative research in Barcelona, I advance multi-dimensional perspectives on precarity by showing how precarious entanglements - where the material, affective, temporal, and spatial become embodied - shape the contours of potentiality and futurity. I conceptualise 'foreclosed futures' as a temporal-affective structure that emerges from, yet unsettles, the logic of Lauren Berlant's 'cruel optimism'. For a generation shaped by austerity, the projection of present structural barriers to upward mobility into the future precludes the imagination of prosperous futures, fostering hopelessness, disillusionment, and nostalgia for lost stability. To unpack this dynamic, I illuminate how persistent precarity resignifies the urban - not as a site of potentiality, but as one of constraint leading to foreclosure of potentiality. I then demonstrate how a sense of inevitable downward mobility and social decline alters the emotions and temporalities tied to post-war ideals of security woven into cruel optimism. Finally, I show how apprehension towards insecure futures anchors young people in present-oriented survival, fostering pragmatic and pessimistic attitudes, concluding with an analysis of the socio-political implications of foreclosed futures.


Air Sensor Network Analysis Tool: R-Shiny Application

Abstract: Poor air quality can harm human health and the environment. Air quality data are needed to understand and reduce exposure to air pollution. Air sensor data can supplement national air monitoring data, allowing for a better understanding of localized air quality and trends. However, these sensors can have limitations, biases, and inaccuracies that must first be controlled to generate data of adequate quality, and analyzing sensor data often requires extensive data analysis. To address these issues, an R-Shiny application has been developed to assist air quality professionals in (1) understanding air sensor data quality through comparison with nearby ambient air reference monitors, (2) applying basic quality assurance and quality control, and (3) understanding local air quality conditions. This tool provides agencies with the ability to more quickly analyze and utilize air sensor data for a variety of purposes while increasing the reproducibility of analyses. While more in-depth custom analysis may still be needed for some sensor types (e.g., advanced correction methods), this tool provides an easy starting place for analysis. This paper highlights two case studies using the tool to explore PM2.5 sensor performance under the conditions of wildfire smoke impacts in the Midwestern United States and the performance of O3 sensors for a year.

Barkjohn KK
Plessel T
Yang J
Pandey G
Xu Y
Krabbe S
Seppanen C
Bichler R
Tran HNQ
Arunachalam S
Clements AL


Predicting hypertension in preeclampsia patients within five years postpartum: analysis of influencing factors and nomogram development

Abstract: Preeclampsia is a pregnancy-related hypertensive disorder with long-term cardiovascular risks. The aim of this study was to explore the factors influencing hypertension progression in preeclampsia patients within 5 years postpartum, and to construct a nomogram. A retrospective study of 280 preeclampsia patients, grouped by hypertension progression status within 5 years postpartum, was performed. Differential analyses compared: 1) demographic/pregnancy characteristics, and 2) late-pregnancy, 1-week-postpartum, and 6-week-postpartum blood indicators between groups. Multiple logistic regression and generalized estimating equations (GEE) identified hypertension progression factors. Significant factors used to construct the nomogram were evaluated via calibration and receiver operating characteristic (ROC) curves in training/test sets. Patients who progressed to hypertension had higher pre-pregnancy and postpartum body mass index (BMI), a greater proportion of early-onset and severe preeclampsia, and a higher incidence of adverse pregnancy outcomes compared to those who did not progress to hypertension. Additionally, they had lower platelet levels during late pregnancy and postpartum, while levels of aspartate aminotransferase, alanine aminotransferase, 24-hour urinary protein, uric acid, and C-reactive protein were higher in patients who did not progress to hypertension. Multivariate logistic regression identified placental abruption, oligohydramnios, and umbilical artery pulsatility index as significant factors, while the generalized estimating equation highlighted uric acid (UA), platelet (PLT), and alanine aminotransferase (ALT) as key predictors. The nomogram demonstrated good predictive performance, as shown by calibration and ROC curves. Hypertension progression correlates with placental abruption, oligohydramnios, elevated umbilical artery pulsatility index (UA-PI), elevated UA, decreased PLT, elevated ALT, and specifically aspartate aminotransferase at 1-week postpartum. The nomogram aids early identification of high-risk patients.


Beneficial effects of antioxidants on neutrophil extracellular trap formation in atherosclerosis

Abstract: Neutrophils have been implicated in the pathogenesis of atherosclerosis in multiple studies. This study aimed to determine the effects of flavonoids (quercetin and luteolin) and vitamin C on neutrophil extracellular trap (NET) formation and regulation of NET markers, including circulating cell-free DNA (cfDNA) and myeloperoxidase (MPO). Additionally, we assessed the expression of NADPH oxidase complex subunits and superoxide anion generation in neutrophils. Whole blood samples were collected from patients with atherosclerosis. Neutrophils were stimulated with lipopolysaccharide (LPS), and the effects of flavonoids and vitamin C on NET release, NADPH oxidase subunit expression (p47phox, p67phox, Rac1), and superoxide production were evaluated. Atherosclerotic patients showed increased NETosis, with elevated NET release, MPO, and cfDNA levels. Expression of NADPH oxidase subunits p47phox and p67phox and superoxide anion generation were significantly higher compared to controls. LPS further enhanced these effects. Treatment with quercetin, luteolin, and vitamin C reduced NET formation, NADPH oxidase expression, and superoxide production in stimulated neutrophils. Flavonoids and vitamin C modulate NET formation, likely by affecting NADPH oxidase activity and reactive oxygen species production, suggesting potential anti-inflammatory effects relevant to atherosclerosis. Further studies are warranted to evaluate the potential application of these compounds as adjunctive therapy in the treatment of atherosclerosis.

Dąbrowska-Zagroba D
Garley M
Ratajczak-Wrona W
Sawicka-Powierza J
Grubczak K
Radziwon P
Wołczyński S
Jabłońska E


Shared decision-making in primary care: barriers and facilitators from the physician's and patient's perspectives: a scoping review

Abstract: Health-related communication and shared decision-making (SDM) are crucial elements of patient-centered care. The aim of this review was to identify the key barriers and facilitators influencing the adoption of an SDM approach from both the physician's and patient's perspectives in primary healthcare in relation to the 5-step model of SDM. A scoping review of resources published within the last 5 years was conducted in June 2024 in accordance with PRISMA-ScR guidelines. Specific barriers hindering the adoption of SDM were identified, which can arise at any of the five steps. The most common barriers include: time constraints and physician's workload, lack of SDM culture and tradition, paternalistic model of healthcare, and patients' passive attitude and belief they are unable to make decisions. SDM facilitators include: trust, use of educational materials by physicians, belief that SDM will lead to better treatment outcomes, and training in communication for physicians. Despite the challenges to public health, action should be taken to overcome these barriers, given the well-established benefits of SDM, although this will require time and necessary adaptations.

Domosławska-Żylińska K
Krysińska-Pisarek M


Secondary cancers in breast cancer survivors. A two-centre study

Abstract: The risk of secondary cancers in breast cancer survivors remains a significant concern. This study aimed to evaluate the association between treatment modalities and the time to development of secondary cancers in patients after mastectomy or breast-conserving therapy (BCT). A retrospective analysis was conducted on 6590 patients from 2 centres (Poznan and Gorzow, Poland) treated for breast cancer between 2017 and 2022. A total of 149 patients from this group developed secondary cancer. Data included demographic and clinical characteristics, treatment types (chemotherapy, hormonotherapy, radiotherapy), and subtypes of primary breast cancer (luminal, triple negative, HER2 positive). Statistical methods included Kaplan-Meier analysis, Cox proportional hazards models, and χ2 tests. The median time to secondary cancer detection was significantly shorter in patients with TNBC/HER2+ subtypes (2.8 years) compared to luminal subtypes (6.1 years; p = 0.024). TNBC/HER2+ subtypes were associated with a 1.9-fold increased risk of secondary cancers (HR = 1.93; p = 0.048). No significant association was found between treatment type and the occurrence of secondary cancers (p > 0.05). However, combined therapies (e.g. chemotherapy + hormonotherapy) showed a trend toward reduced risk (HR = 0.53; p = 0.061). The most common secondary cancers were gastrointestinal malignancies (27%) and gynaecological cancers (15%). The subtype of primary breast cancer significantly influences the time to secondary cancer development, with TNBC/HER2+ patients at higher risk. Treatment modalities did not significantly affect secondary cancer risk, but combined therapies may offer protective effects. These findings highlight the need for tailored surveillance strategies based on tumour biology.

Wichtowski M
Gibowska-Maruniak P
Bigos P
Urbański Ł
Gryczka H
Bujko-Wasiak N
Milecki T
Pytlak K
Kurzawa P
Brzeźniakiewicz-Janus K
Gil L


The association of low-density lipoprotein cholesterol with apolipoprotein B ratio and sarcopenia: a cross-sectional study

Abstract: Sarcopenia is increasingly linked to metabolic dysregulation, including dyslipidemia. The low-density lipoprotein cholesterol with apolipoprotein B (LDL-C/ApoB) ratio (LAR), reflecting cholesterol content per atherogenic lipoprotein particle, may serve as a novel biomarker for sarcopenia risk. This study aimed to investigate the association between LAR and sarcopenia using data from the National Health and Nutrition Examination Survey (NHANES). Data from NHANES cycles 2011-2016 were analyzed between July 2024 and February 2025. Sarcopenia was defined using dual-energy X-ray absorptiometry (DXA)-derived appendicular lean mass (ALM) standardized to body mass index (BMI). Multivariable logistic regression, restricted cubic spline (RCS) regression analysis, subgroup analysis, and interaction tests were applied to evaluate the relationship between LAR and sarcopenia, adjusting for covariates. A negative correlation between LAR and sarcopenia was observed in 3,235 participants included in the study (OR = 0.399, 95% CI: 0.224-0.712, p = 0.007), which was further confirmed to be non-linear via RCS regression analysis (p non-linear = 0.037), with one significant inflection point identified, and participants with LAR ≥ 1.268 demonstrated a significantly reduced risk of sarcopenia. Subgroup analyses and interaction tests indicated that the association between LAR and sarcopenia remained consistent across different subgroups and was not modified by other covariates. Elevated LAR is significantly associated with lower sarcopenia risk, suggesting its potential role as a biomarker for muscle health. Further studies are needed to elucidate underlying mechanisms and validate these findings prospectively.


Plasma proteome-genome integration reveals novel protein biomarkers and therapeutic targets linked to breast cancer survival

Abstract: Identifying new drug targets is essential for improving breast cancer survival. The proteome provides a rich source for potential therapeutic targets. This study aimed to identify protein markers and therapeutic targets for breast cancer by using proteome-wide Mendelian randomization (MR). Protein quantitative trait loci (pQTL) data were obtained from four large-scale proteomic studies, including 17,267 circulating protein markers. Genetic associations with breast cancer survival were derived from a large-scale GWAS meta-analysis (37,954 cases, 2,900 deaths). Proteome-wide MR was performed to estimate causal effects of proteins on breast cancer survival, complemented by single-cell expression analysis to identify enriched cell types. Protein-protein interactions (PPI) and druggability assessments were also conducted to prioritize therapeutic targets. Genetically predicted circulating levels of 27 proteins were found to be associated with breast cancer survival. Among these, eight proteins (ADAM15, CD83, SH3BGRL3, SNCG, ANXA1, GRHPR, ALDH2, and MTHFD2) showed the strongest evidence of association, while four proteins (ARG2, RPL14, NFU1, and TXNL4B) demonstrated a strong but slightly weaker correlation. Notably, SH3BGRL3, GRHPR, ARG2, RPL14, NFU1, and TXNL4B were newly identified as circulating protein markers significantly associated with breast cancer prognosis. Druggability analysis revealed that 13 of these proteins were already targeted by existing drugs, offering potential for breast cancer treatment. We identified 27 genes encoding proteins associated with overall and subtype-specific breast cancer survival, providing potential prognostic biomarkers and therapeutic targets, and offering new avenues for improving breast cancer management.


Causal effects of physical activity and frailty on pneumothorax risk: a Mendelian randomization study

Abstract: Pneumothorax is the presence of air in the pleural cavity, often resulting in respiratory distress and impaired lung function. Although clinical observations have shown that high intensity physical activity and frail state affect respiratory health, their causal role in pneumothorax development is unclear. This study is the first to use a two-sample Mendelian randomization method (TSMR) to investigate the causal relationship between physical activity and frailty and the risk of pneumothorax, with a view to providing new insights into the pathogenesis of pneumothorax and preventive strategies. Using Mendelian randomization (MR) analyses, we examined the potential causal relationship between physical activity, frailty, and the risk of pneumothorax. Genetic instrumental variables (IVs) for relevant exposure factors were selected from genome wide association studies (GWAS). The study was analyzed using five different methods, mainly using inverse variance weighted (IVW) to draw causal inferences. Sensitivity analyses were performed to ensure the validity of the MR results. Sensitivity analyses included the detection of horizontal pleiotropy, i.e., genetic variants affecting the outcome through pathways other than the target exposure, which may lead to biased causal inference. Heterogeneity between genetic instrumental variables was also assessed and used to detect variability in effect estimates, which may reflect violations of MR assumptions or differences between populations. Our analyses found that light DIY reduced the risk of pneumothorax, but did not identify a causal association between other levels of physical activity and pneumothorax. In addition, frailty index (FI) showed a positive association with the risk of developing spontaneous pneumothorax, and this causal relationship persisted after adjustment for body mass index (BMI) and light DIY. Sensitivity analyses further validate the robustness of our findings. Our findings support the ability of light DIY to reduce the risk of pneumothorax development. It also emphasizes the need for frail individuals to be more aware of the need to protect against pneumothorax in their daily lives. We encourage appropriate exercise to improve fitness and reduce the risk of pneumothorax.


Establishing Hemodynamic Convergence Framework for Coronary Digital Twins Under Realistic Dynamic Heart Rates

Abstract: The advent of digital twins has increased the demand for longer-duration simulations that span multiple physiological states. Digital twins have emerged as powerful tools in cardiovascular modeling, enabling patient-specific simulations of coronary blood flow for non-invasive diagnosis and treatment planning. Although these simulations achieve high fidelity under steady or periodic heart rates, modeling real-world transitions, such as those arising from physical activity, requires careful evaluation of temporal convergence, the stabilization of hemodynamic parameters through the simulation of preceding cardiac cycles, or 'pre-flows'. In this study, we present a physiologically grounded approach for determining the minimum number of preceding cardiac pre-flows necessary to achieve temporal convergence following abrupt heart rate (HR) changes. Using high-resolution patient-specific 3-dimensional (3D) simulations and inflow waveforms scaled from both synthetic and wearable-derived HR data, we quantify convergence behavior across velocity, pressure gradient, and wall shear stress at both cross-sectional and full-domain levels. Results show that simulating just two pre-flows is sufficient to achieve physiologically stable outputs across high-to-low and low-to-high HR transitions (<2% difference). These findings are further verified using continuous HR data obtained from wearable devices, with low and high HR segments extracted to represent natural extremes, confirming the robustness of the proposed convergence criterion under real-world dynamic inputs (<1% difference). This work establishes a computationally efficient and physiologically consistent criterion for dynamic-state simulations, facilitating the integration of cardiovascular digital twins with real-time sensing technologies.

Physics of fluids (Woodbury, N.Y. : 1994)


Hypertension and ovarian cancer risk: a meta-analysis of observational studies

Abstract: Ovarian cancer is the eighth most common cancer among women and an important cause of cancer-related mortality, particularly in high-income countries. Scientific studies show that hypertension may play a significant role in the initiation of cancer. Therefore, we conducted the first meta-analysis to comprehensively examine the association between hypertension and ovarian cancer risk. We performed a literature search of all of the observational studies published as original articles from inception to July 2024, and we searched the following electronic databases: PubMed, Embase, and Cochrane Library. Finally, we included ten full-text cohort and case-control studies addressing the effect of hypertension on ovarian cancer in this meta-analysis. Our study was preregistered with International Prospective Register of Systematic Reviews (PROSPERO CRD42024565574) and followed the PRISMA statement. Effect size was presented as risk ratios (RRs) and 95% confidence intervals (CIs). Heterogeneity test evaluation was performed using Cochran's Q test and I 2 statistics. The meta-analysis included a total of 2,497,898 women. There was a statistically significant association (RR = 1.10, 95% CI: 1.02-1.23, p < 0.011) between hypertension and ovarian cancer risk. Subgroup analysis showed that parity may significantly reduce the ovarian cancer risk, which was higher among women who had never given birth (RR = 1.43, p < 0.0025), while a body mass index (BMI) > 25 kg/m2 increased the risk of ovarian cancer (RR = 1.12, p < 0.0001). The findings of this comprehensive review and meta-analysis indicate that hypertension is associated with higher overall risk of ovarian cancer. While the present data provide novel evidence, further prospective studies are needed to elucidate the association between hypertension and ovarian cancer risk.

Drab A
Wdowiak K
Kanadys W
Malm M
Dolar-Szczasny J
Religioni U


Key technical aspects and vascular access safety in membrane-based therapeutic plasma exchange for the pediatric population

Abstract: Therapeutic plasma exchange (TPE) is a widely used extracorporeal blood purification procedure. While its principles are similar across age groups, the technical complexity and risks are heightened in pediatric patients due to unique technical considerations. This study assessed the safety regarding both technical and clinical complications of vascular access and membrane-based TPE filters in a pediatric population at a single center. This retrospective cohort study reviewed charts of patients undergoing TPE at a level 3 referral center over 25 years. The study involved 178 patients undergoing a total of 740 procedures during 214 sessions, predominantly using femoral vascular access. The median duration of the entire TPE sessions (treated as a surrogate for catheter lifespan) was 118.5 h. Technical complications occurred in 20.8% of procedures (31.6% of events), while clinical complications occurred in 4.2% (4.7% of events). Technical complications were nearly five times more frequent than clinical complications, with technical events being 6.7 times more common. The proportion of patients experiencing clinical complications was 15.2%. Logistic regression demonstrated that each additional day of catheter placement increased the probability of technical complications by 3%. Additionally, each year of patient age decreased the likelihood of clinical complications by 8.9%, while fresh frozen plasma (FFP) supplementation within a session increased the probability of clinical complications by 21.6%. Prolonged catheter use increases technical events, while FFP supplementation elevates catheter-related clinical complication risk. Advancing patient age reduces the likelihood of clinical complications, underscoring age-specific safety considerations in pediatric TPE.

Błasiak M
Korohoda P
Zachwieja K
Drożdż D
Madej-Świątkowska K
Jarosz-Wójcik E
Miklaszewska M


Association between Diabetes-Related Distress and Medication Adherence among Patients with Type 2 Diabetes Mellitus, Southwest Nigerian

Abstract: Diabetes-related distress is a common complication that usually impacts the well-being, health outcomes and adherence to medications, especially in individuals with type 2 diabetes mellitus (T2DM). Hence, this study aimed to estimate diabetes-related-distress and its association with medication adherence. This is a hospital-based cross-sectional study conducted among 135 patients with T2DM recruited consecutively from a diabetes clinic of a tertiary health institution, Southwest, Nigeria, from March to September 2022. Data were obtained using the Diabetes Distress Scale (DSS-17) questionnaire and Morisky's Medication Adherence Scale (MMAS-8). The association between the dependent variable (DRD) and the independent variable (medication adherence) was assessed with chi-square, and predictors of DSS with logistic regression analysis. The ethical approval was obtained from the committee of the hospital. The mean age of study participants, and duration of diabetes were 62.20 ± 12.80 years and 7.96 ±7.01 years, respectively. The proportion of diabetes distress among the study population was 30.5% (8.3 % had high distress and 22.2 % moderate distress). Poor adherence to medications was 66.5%. The study showed that diabetes-related distress was associated with poor medication adherence ( χ2 =9.251, p=0.010). Patients who were highly distressed had 56% lower odds of adhering to their medications compared to those who were not (OR: 0.32, 95% CI: 0.15-0.62). Our findings suggest that diabetes distress is a common issue and significantly determines medication adherence. Thus, incorporating routine screening for distress into the standard diabetes care will be an important intervention to improve adherence and health outcomes of people living with T2DM.

Nigerian medical journal : journal of the Nigeria Medical Association

Olamoyegun MA
Ojo OA
Akinlade AT
Olaniyi P


Cardiac involvement in immune-mediated necrotizing myopathy: a case report with insights from cardiac magnetic resonance imaging

Abstract: Immune-mediated necrotising myopathy (IMNM) is a rare autoimmune disease recently recognised as part of the spectrum of idiopathic inflammatory myopathies. Although cardiac involvement is a prominent extramuscular manifestation in anti-signal recognition particle (SRP) IMNM, there remains a lack of sufficient cardiac magnetic resonance imaging data. Here, we present a case of anti-SRP IMNM with cardiac involvement as the initial symptom, utilising imaging assessments at various stages of the disease to evaluate and monitor disease progression and treatment response. These findings may provide valuable insights for the clinical identification and management of anti-SRP IMNM with cardiac involvement.


The Use of "FetalKickApp" for Counting Fetal Movement in Pregnant Women: A Case Study of The University of Port Harcourt Teaching Hospital, Nigeria

Abstract: The global stillbirth rate is 13.9 stillbirths per 1000 births, with most stillbirths being recorded in developing countries. Most cases of stillbirth are preceded by reduced fetal movement. Early detection of reduced fetal movement is a key element in reducing the number of stillbirths. Therefore, a "FetalkickApp" that is a self-monitoring digital health tool, assists a pregnant woman to count, record, and send her fetal movement count to her health care provider without the use of mobile data or internet. This study is a longitudinal pilot study involving 25 pregnant women with single fetuses between 28 and 38 weeks of gestation. The mobile application monitor was used to record the number of fetal movements for 4 weeks. A 5-point Likert scale questionnaire is used to assess the use of the application, interface experience, satisfaction with the design, and function of the application without internet. The mean age of the women is 31.2 (±4.5) years, and the mean gestational age is 29.5 (±2.4) weeks. The results obtained show that the majority of the women (72%) had good knowledge of fetal movement. About two-thirds (64%) of the women agreed that the FetalkickApp is helpful in counting their fetal movement. Forty-four per cent (44%) of the women strongly agreed that the application is easy to use, and 68% of the women agreed that the FetalkickApp's effectiveness is satisfactory. The FetalkickApp is independent of the internet, which means that it could be used everywhere. The interface and design of the application are simple and could be operated by any individual concerned.

Woruka AP
Wells A
Lekpa D
Adewuyi P
Oluwole Z
Echefu L
Tobechukwu EM
Okerim CF


A handful of inflammation

Abstract: Rheumatoid arthritis is an autoimmune disease typically affecting the metacarpophalangeal (MCP) and proximal interphalangeal (PIP) joints as well as larger joints like the wrists, shoulders or knees. We present a case of a 49-year-old woman with symmetrical pain not only in her knees, shoulders, wrists, and MCP and PIP joints but also in her distal interphalangeal (DIP) joints. She has elevated levels of rheumatoid factor and anticitrullinated protein antibodies and a highly active arthritis on magnetic resonance imaging of her right hand in the wrist, MCP, PIP, and 3 out of 4 DIP joints. In summary, we diagnosed a seropositive rheumatoid arthritis affecting all but 1 joint of her hand. This case highlights the very rare (less than 0.2%) affection of 3 out of 4 DIP joints in rheumatoid arthritis.

Witte T
Albach F
Simon D
Kleyer A
Biesen R
Hermann KG


Ambient AI scribes in rheumatology: early real-world clinician and patient experience


Gastrointestinal Ascariasis: Unusual Presentation in 2 Cases

Abstract: Ascariasis is a helminthic infection caused by the nematode Ascaris lumbricoides and remains the most prevalent helminth infection worldwide. Although typically asymptomatic or limited to intestinal symptoms, intestinal ascariasis can present unusually as demonstrated in these two cases. The first case involves a 73-year-old male who was being treated for non-steroidal anti-inflammatory drug (NSAID) - induced upper gastrointestinal bleeding (UGIB) and was incidentally found to harbor Ascaris worms in the duodenum during endoscopy. The second case describes a 63-year-old male with decompensated liver cirrhosis who began vomiting and passing large quantities of Ascaris worms while hospitalized. Both patients responded excellently to anthelminthic therapy. The first case highlights the need to consider ascariasis in the differential diagnosis of upper gastrointestinal bleeding, either as a primary cause or in conjunction with other causes of upper GI bleeding. The second case underscores the importance of considering biliary ascariasis or ascariasis co-infection in patients with liver cirrhosis. Ascariasis continues to pose a significant public health challenge. Effective preventive strategies such as improved sanitation, enhanced personal hygiene, and routine deworming programs are crucial for reducing the disease burden and averting potentially severe complications.

Duruewuru UP
Chukwurah SN
Nnemelu OP
Nduaguba TS
Nwafor EN
Ogbonna KE
Ilika CV


Prevalence, outcomes, and predictive factors: a systematic literature review to inform the development of EULAR Points to Consider for the definition of Difficult-to-Manage and Treatment-Refractory psoriatic arthritis

Abstract: To perform a systematic literature review (SLR) to inform the EULAR Task Force "Points to Consider for the definitions of Difficult-to-Manage (D2M) and Treatment-Refractory (TR) psoriatic arthritis (PsA)". The SLR addressed 3 separate questions concerning the following: (1) prevalence, (2) outcomes, and (3) predictors of D2M/TR PsA. A search was conducted in MEDLINE (Ovid), Cochrane Database of Systematic Reviews, CENTRAL, EMBASE, and Epistemonikos from inception to March 3, 2024, as well as EULAR/ACR abstracts for 2023/24 and 2022/23, respectively. This systematic review adhered to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and was registered on PROSPERO. Data are summarised descriptively. Meta-analysis was not possible due to significant heterogeneity and/or lack of high-quality evidence. Risk of bias (RoB) was assessed using the Newcastle-Ottawa Scale. Overall, 70, 4, and 25 articles/abstracts were included for questions 1, 2, and 3, respectively. For question 1, 30/70 records had low/moderate RoB, with the prevalence of D2T PsA ranging from 5% to 80% depending on both the timepoint at which prevalence was measured and the definition of D2M/TR PsA applied, which varied significantly between studies. For question 2, all records had a high RoB; therefore, no conclusions could be drawn. For question 3, all records had a moderate RoB, and 84 categories of potential predictors were identified, with large differences in strength and direction of association between studies. Despite significant heterogeneity in the published literature regarding the scope, definition, long-term outcomes, and predictors of D2M/TR PsA, certain patterns emerged that helped shape the final EULAR Task Force recommendations.

Harrison SR
Fragoulis GE
Michelena X
Macía-Villa C
Falzon L
Siebert S
Marzo-Ortega H
Sepriano A
Machado PM


Rapid and profound treatment response of difficult-to-treat rheumatoid arthritis to CD19 CAR T-cell therapy

Albach FN
Minopoulou I
Wilhelm A
Kleyer A
Wiebe E
Fleischmann A
Engel K
Frick M
Damm F
Gogolok J
Serve S
Locher B
Borie D
Phithak E
Hinkelmann L
Ohrndorf S
Casteleyn V
Biesen R
Sattler A
Dörner T
Drzeniek NM
Alexander T
Zernicke J
Unterwalder N
Movassaghi K
Hütter-Krönke ML
Schrezenmeier E
Schreiber A
Furth C
Schett G
Schneider U
Bullinger L
Krönke G
Penack O
Simon D


Clinical, biological, and radiological changes under therapy, and criteria for clinical response and remission in adult-onset Still's disease: a systematic literature review informing the development of the European Alliance of Associations for Rheumatology (EULAR) criteria for assessing disease activity

Abstract: A task force commissioned by the European Alliance of Associations for Rheumatology was set up for the Development And Validation of a composite disease actIvity score in adult-onset Still's Disease (AOSD) (CLI113). A systematic literature review was undertaken to extract evidence regarding the disease activity assessment in AOSD and to identify potential candidate variables to be included in the criteria for the assessment of disease activity. The PubMed MEDLINE, EMBASE, and Web of Science databases were screened for eligible articles published between January 1990 and September 2021. Abstracts from 2018 to 2021 EULAR, ACR, and ISSAID conferences were also browsed. We included randomised controlled trials (RCTs), quasi-RCTs, cohort studies and case series of ≥ 4 patients describing changes under therapy, with a minimum follow-up of 4 weeks. The risk of bias was assessed using the National Institute of Health Quality Assessment Tool. Results were synthesised descriptively. Sixty-three studies (including 2889 patients) were selected. Four were RCTs or quasi-RCTs, and 59 were observational studies. Most of the studies were retrospective (n = 58) and of poor quality. The most often reported clinical characteristics were fever, cutaneous rash, arthralgia and/or arthritis, hepatosplenomegaly, and sore throat. The most often reported laboratory parameters were leukocyte count, erythrocyte sedimentation rate, serum C-reactive protein and ferritin levels, all of which decreased with treatment. Definitions of response, remission and relapse, disease activity composite indices and patient-reported outcomes were heterogeneous. Based on the identified variables, we can aim for a subsequent establishment and validation of a new measure to improve and standardise the management of patients with AOSD.

Girard-Guyonvarc'h C
Mitrovic S
Ruscitti P
Fautrel B
Gabay C
Gonzalez-Gay MÁ
Feist E
Giacomelli R
Stamm T
EULAR Task Force CLI113


Items identified by expert physicians for the development of the criteria for the assessment of disease activity for adult-onset Still's disease: results of a web-based Delphi study informing the development of the European Alliance of Associations for Rheumatology (EULAR) criteria for the assessment of disease activity in these patients

Abstract: The assessment of activity in adult-onset Still's disease (AOSD) remains difficult because of no validated score for this disease. A task force commissioned by the European Alliance of Associations for Rheumatology (EULAR) undertook a 3-round consensus-building study to elicit items to be included in the criteria for the assessment of disease activity for AOSD. Candidate items were initially extracted from a systematic literature review, and additional items were collected from expert physicians' answers to open-ended questions during the first Delphi round via a web-based application. In the second round, the expert physicians scored items for relevance. Subsequently, the expert physicians were presented the results of the group ratings and asked to score again in the third and final Delphi round. The cutoff for including an item in the criteria for the assessment of disease activity was set at ≥75% for the top 2 ratings ('absolutely required' and 'important'). In total, 25 expert physicians from 7 countries participated in all 3 Delphi rounds. A total of 28 candidate items were initially identified. In the final expert rating, the 14 following items were above the cutoff: fever, cutaneous rash, arthralgia, arthritis, splenomegaly, lymphadenopathies, pleuritis, pericarditis, white blood cell count ≥10,000/mm3, polymorphonuclear cells ≥80% of white blood cell count, increased erythrocyte sedimentation rate, increased serum C-reactive protein level, increased serum ferritin level, and elevated liver enzyme levels. The study is the first part of the development and validation of the criteria for the assessment of disease activity in AOSD.

Mitrovic S
Girard-Guyonvarc'h C
Ruscitti P
Gabay C
Gonzalez-Gay MÁ
Feist E
Giacomelli R
Stamm T
Fautrel B
EULAR Task Force “CLI113”


Canakinumab for systemic-onset juvenile idiopathic arthritis/Still's disease-effectiveness and safety data from the BiKeR registry

Abstract: In Germany, canakinumab is approved for the treatment of refractory systemic juvenile idiopathic arthritis (sJIA)/Still's disease. This study assesses the experience of sJIA/Still's disease patients treated with canakinumab in clinical practice. Data of 79 sJIA/Still's disease patients extracted from the BiKeR registry included patients' and disease characteristics. Three subgroups with disease durations before canakinumab initiation of ≤3 months, >3 to ≤12 months, and >12 months were compared, and 2 with canakinumab as first- and second- or more-line treatment. Disease duration was ≤3 months before canakinumab initiation for 26 patients, >3 to ≤12 months for 24 patients, and >12 months for 29 patients. Thirty-nine patients received canakinumab as first-line treatment and 40 as second- or more-line treatment. Disease severity as assessed by the systemic Juvenile Arthritis Disease Activity Score-10 (sJADAS10) was highest for patients with a disease duration <3 months before canakinumab initiation. In the total cohort, after 3, 6, 12, 18, and 24 months, 86%, 81%, 81%, 75%, and 87% of patients reached inactive disease, respectively. Numerically, more patients reached the treatment goal of inactive disease when the disease duration was shorter before initiation of canakinumab. Minimal disease activity (sJADAS10 ≤6.0) did not differ among subgroups. Compared with second-line, more patients with first-line treatment reached inactive disease at months 6, 12, and 24 after canakinumab initiation. sJADAS10 at 12 months correlated significantly with disease duration before treatment. Canakinumab treatment led to high improvement rates and achievement of inactive disease state, particularly if they are administered early. Data from clinical practice confirm clinical study data.

Horneff G
Kallinich T
Minden K
Dressler F
Hufnagel M
Weller-Heinemann F
Klein A


Exploring Access to Psychedelics Among Canadian Veterans: Pathways, Barriers, and Perceptions

Abstract: Psychedelic-assisted therapies have recently gained attention as potential novel treatments for various mental health conditions. In Canada, there has been particular interest from the veteran communities regarding the potential therapeutic impact of psychedelics. However, legal access remains limited in Canada, leading some veterans to explore alternative pathways. Here, we aimed to explore how Canadian military veterans learn about and access psychedelics for mental health treatment. Using a retrospective survey-based design in collaboration with the registered Canadian charity, Heroic Hearts Canada, we collected data from 30 veterans on their mental health history, prior treatments, information sources, and methods of access. Our findings indicate that while some veterans accessed psychedelics through legal pathways (20%, N = 5), most sought them through underground options, including self-directed (64%, N = 16) and guided experiences within (44%, N = 11) and outside (20%, N = 5) Canada. Veterans primarily relied on peers (73.3%, N = 22) and media (53.3%, N = 16) for information rather than health care providers (10%, N = 3). Those who avoided discussions with their health care providers cited concerns about stigma (64%, N = 9/14), while those who did consult health care providers often found them to lack knowledge on psychedelic treatments (69%, N = 11). These findings highlight gaps in access and education surrounding psychedelic therapies for veterans. While interest in these therapies is growing, it is important to note that clinical use of psychedelics for mental health conditions remains investigational. We propose that addressing these barriers through improved clinician training and education, policy reform, and development of safer legal pathways may support more informed and cautious engagement with these treatments and is essential to ensuring informed and effective care for those seeking alternative mental health treatments, such as psychedelics. Moreover, these efforts will contribute to broader harm reduction strategies by equipping clinicians with the knowledge and tools to support individuals who may continue to access these substances outside legal frameworks.

Psychedelic medicine (New Rochelle, N.Y.)

Contreras LE
Elliott GO
Kment F
Scott MA
Fascinato D
Mayo LM


Lupus trials and tribulations: are outcome measures the problem?

Abstract: Many randomised clinical trials in systemic lupus erythematosus have failed, and the manner in which they have failed is of concern. In lupus, phase III trials have a higher risk of failing than phase II trials-going against the expected gradient and against logic, because phase III trials are preferentially based on successful rather than on failed phase II trials. In addition, there have been puzzling discrepancies between different outcomes within individual trials as well as between the same outcomes in different trials. Therefore, it has been suggested that outcome measures are to blame for the difficulties in achieving trial successes in lupus. Additional concerns regarding clinical trial outcomes deal with their complexity and lack of clinical applicability; and the most widely used trial outcomes, SRI-4 (systemic lupus response index [based on four points improvement]) and BICLA (British Isles Lupus Assessment Group-Based Composite Lupus Assessment), are at odds with current therapeutic thinking, which is less concerned with change and more with the disease state that is achieved (treating to target). A number of suggestions have been made, and concrete initiatives launched, to address these issues, and these may change the way in which clinical trials will be done in the future. Meanwhile, it is worth mentioning that a large number of phase III trials are currently underway; their outcomes may yet again change the way we approach clinical trial outcomes in lupus.


Swimming-induced pulmonary oedema in triathletes: A narrative review of epidemiology, risk factors and prevention

Abstract: Swimming-induced pulmonary oedema (SIPO) has predominantly been reported in swimmers. However, to date, no review has specifically explored the scientific literature concerning the occurrence and characteristics of SIPO in triathletes. Therefore, this review aims to summarize and discuss the current evidence on SIPO in the context of triathlon. We conducted a narrative review to summarize the current scientific literature on SIPO in triathletes. A structured search of two major databases-PubMed and Scopus-was conducted using free-text terms related to SIPO and triathlon. The search included articles published up to January 2025, with no language restrictions. After removing duplicates and excluding animal or in vitro studies, as well as unrelated articles based on title and abstract screening, a total of 48 relevant publications were included for analysis. The reports on SIPO in triathletes are mainly case reports or case studies on a single athlete or a small number (case series) of triathletes. Most reported cases involved middle-aged women (30-60 years) participating in IRONMAN® 70.3 and IRONMAN® triathlons. The prevalence of SIPO in triathletes is reported to be less than 1.5%. Risk factors for SIPO in triathletes are female sex, age over 50 years, hypertension, fish oil consumption, highly trained individuals, competitive exercise, wet suit compression, longer race distances (i.e. IRONMAN® 70.3 or IRONMAN®) and a cold (water) environment. The symptoms and outcome are similar to those observed in swimmers and other aquatic athletes. In summary, the results regarding the prevalence, symptoms and risk factors of SIPO in triathletes are comparable to those in other aquatic athletes. SIPO occurs only in IRONMAN® 70.3 and IRONMAN® races, but has not been reported in the Olympic distance triathlon or triathlons longer than the IRONMAN® race distance.

Knechtle B
Nikolaidis PT
Chlíbková D
Bernardes Leite L
Forte P
Santos Andrade M
Weiss K
Rosemann T
Duric S


Challenges and opportunities of catalytic decomposition of ozone at room temperature

Abstract: Catalytic decomposition is a key technology for the removal of ozone (O3). Practical application scenarios require catalysts with superior O3 decomposition performance at ambient temperatures, high humidity, and high space velocities. In this review, the strategies for the design of catalysts with efficient and stable O3 decomposition performance are presented, and the three factors that limit the catalytic decomposition of O3 at ambient temperature (insufficient active sites, competitive adsorption of H2O and O3 molecules, and difficult desorption of intermediate oxygen species) are systematically summarized for the first time. Subsequently, the research progress in recent years is categorized and summarized in terms of addressing the three factors limiting O3 decomposition, which in turn suggests the shortcomings of current research and the focus of future research.


The relationship between circulating osteocalcin and muscle mass measurements in humans: A systematic review and meta-analysis

Abstract: Osteocalcin (OC) and the undercarboxylated form (ucOC) are bone-derived peptide hormones produced by osteoblasts that are involved in systemic metabolism and skeletal muscle mass regulation. Human studies have been equivocal regarding the relationship of circulating OC with muscle mass. Our aim was to summarize the published findings on the relationship between OC levels and muscle mass measurements in humans and determine if factors such as age and sex impact the outcome. PubMed, Scopus, and CINHAL databases were systematically searched to identify empirical human studies reporting the correlation coefficients between OC levels and measures of muscle mass. Muscle mass measurements included total body lean mass (tLM), percent lean mass (%LM), appendicular lean mass (aLM), and lean muscle index (LMI). Studies were included in the meta-analysis, with effect sizes being extracted for total OC (tOC) and ucOC. Subgroup analyses examined age, sex, and health status. Muscle mass quantified by %LM had a significant correlation with tOC and ucOC. LMI had a significant correlation with ucOC, but not tLM, and aLM. There was a weak, significant positive association between tOC and ucOC with all combined muscle mass measurements, and the relationship with tOC was more evident in male adults. Circulating OC, specifically ucOC, had a significant relationship with %LM, but not tLM or aLM. Circulating OC appears to be more closely associated with body composition than with total mass. Further studies are needed to determine how age and sex interact with OC regulation of body composition.


Challenges and fundamental theoretical problems of super-converged generative information network

Abstract: Super-converged generative information network (SoGIN) envisions the integration of human-physical and digital networks, with development requirements centered on space-air-ground integration, computing-storage-sensing-intelligence integration, and availability-reliability-trustworthiness integration. Following the new development paradigm of decoupling network support environments from application network systems, SoGIN would build an AI-empowered, highly integrated, efficiently collaborative, trustworthy intelligent information network system based on the deep integration of digital-operation-information-communication technology (DOICT). This provides the foundational support environment for realizing 6G visions. This paper discusses the challenges and fundamental theoretical issues faced by SoGIN. Firstly, the development vision and demands of SoGIN are elaborated. Then, the theoretical and technical challenges in achieving the vision of SoGIN are analyzed. Finally, related theoretical and technical practices about polymorphic network environments, cloud-native-based super-converged network infrastructures, new cybersecurity paradigm, cyberspace resilience empowered by endogenous security and safety (ESS), and the physical foundation of next-generation digital systems technology based on wafer-level computing are described.

Wu J
Ji X
Huang K
Chen Y
Li D
Zhang W
Yang J
Hu Y
Shen J


Group Retreat Psilocybin Therapy for People with Metastatic Cancer with Anxiety and Depression: A Rite of Passage Facilitation Model for a Phase 1/2 Study

Abstract: Psilocybin therapy is an emerging treatment for cancer-related anxiety, depression, and existential distress. Most clinical trials to date have studied individual models of psilocybin therapy, but group models may offer increased access and benefits of community. This technical report describes a group facilitation model developed for an food and drug administration (FDA)-approved Phase 1 to 2 clinical trial that recruited people with metastatic cancer who had moderate or severe symptoms of anxiety or depression in which psilocybin was administered at a 3-day, in-person retreat. The facilitation model we developed for this intervention is based on anthropological studies of ritual, specifically rites of passage, to develop a secular ritual with therapeutic aims. Using rites of passage terminology, "separation" corresponds to preparation, "liminal" corresponds to the psilocybin dosing session, and "reincorporation" corresponds to integration. In our usage, the term "ritual" refers to intentionally structured, symbolic acts that embody and reinforce shared meaning, guiding participants through experiences that may otherwise feel unbounded or overwhelming. In the group psilocybin retreat model, ritual functions both psychologically-by supporting emotional regulation, orientation, and meaning-making-and communally-by embedding the individual's process within a shared field of intention and care. To our knowledge this is the first FDA-approved clinical trial of a secular ritual-based group facilitation model for psychedelic therapy that is associated with empirically demonstrated safety and efficacy outcomes.

Back AL
McGregor BA
Billingsley L
Blom D
Callan G
Myers S
Guy J
Kumar S
Layer M
Levin J
Perez J
Thompson P
Salmonson K
Whinney J
Thorn LL


Regeneration from seeds with physical defects: Contrasts in survival strategies in recalcitrant and orthodox seeds

Abstract: Seeds with different desiccation tolerance and their foraging animals present unique strategies for ensuring population growth and ecological fitness in the natural environment. While some seeds minimize physical injuries by having lignified thick coats or defensive compounds, others tolerate a certain degree of mass loss, with larger seeds enduring partial animal consumption better than smaller seeds, consistent with the reserve effect hypothesis, regardless of their desiccation tolerance. In endozoochory, aerial, terrestrial and aquatic fauna with appropriate gape sizes that consume whole fruits with mostly orthodox seeds are important for longer-distance seed dispersal as long as seed viability suffers little impairment following defecation. Some seeds even gain benefits from animal consumption when physical dormancy is overcome and germination occurs earlier. Dung beetles perform secondary spread and burial of seeds, reducing plant aggregation. On the other hand, highly nutritious recalcitrant seeds of a limited number of plant species show sprouting despite partial loss of embryonic axes to browsing animals, often with damage to radicles being less critical than to plumules. Some recalcitrant seeds even possess the unique ability to regenerate roots and shoots from the cotyledonary tissues devoid of embryonic axes. Such embryonic cell development, or 'stemness', from seed tissue fraction is rare in the plant kingdom, but evidently present in at least four families. Plant regeneration despite seed predation is a multi-trait adaptation that ensures species survival and fosters resilient natural ecosystems.


A brief guideline for the studies of structure-function relationship of ion channels using AlphaFold3

Abstract: Ion channels are crucial membrane proteins that regulate ion flux, thus affecting a broad range of physiological processes and disease mechanisms. Traditional approaches, such as X-ray crystallography and cryo-electron microscopy, often face significant challenges in resolving the structure-function relationships of ion channels due to the complex subunit assemblies, transient functional states, and high experimental costs. AlphaFold3 offers a major leap forward by accurately modeling multimeric channels, predicting ligand and ion interactions, and refining subunit interfaces. Building on AlphaFold2, it integrates diffusion-based algorithms and enhanced confidence metrics to explore gating, auxiliary subunits, disease-linked mutations, etc. This review outlines AlphaFold3's key innovations and provides a step-by-step protocol for its use in predicting ion channel complexes. We discuss essential structural parameters, common software for basic analyses, and complementary techniques including molecular dynamics simulations, molecular docking, functional assays (electrophysiology and ion imaging) and structure biology techniques that extend and validate computational findings. Representative examples, including the P2X receptors and voltage-gated calcium channels, demonstrate AlphaFold3's ability to clarify channel assembly, gating mechanisms, channelopathies, and therapeutic opportunities. Finally, we address AlphaFold3's remaining limitations. Despite these hurdles, AlphaFold3 offers a transformative platform that, when integrated with established experimental methods, is poised to significantly advance ion channel research and drug discovery.


A Nature-Themed Video Intervention Increases Nature Relatedness in Psilocybin-Assisted Psychotherapy for Alcohol Use Disorder

Abstract: Psychedelic-assisted psychotherapy has shown promising results for treating alcohol use disorder (AUD) and other mental health conditions. Although the precise mechanisms of psychedelic therapies remain unclear, many studies report increased feelings of connectedness following psychedelic experiences. Specifically, both nature relatedness (one's subjective sense of being connected to nature) and social connectedness (feelings of comprehensive social closeness) have been shown to increase with psychedelic use, and greater connectedness in these domains has been associated with enhanced health and well-being. The current study examined whether a nature-themed video intervention presented to participants undergoing psilocybin-assisted psychotherapy would differentially affect nature relatedness compared with social connectedness in adults with AUD. A total of 20 participants were randomized to either the visual healing condition (viewing a 42-min nature video; N = 10) or the standard setting condition (guided body scan; music with eyeshades; N = 10). Nature relatedness and social connectedness were measured using the Nature Relatedness Scale (NRS-6) and the Social Connectedness Scale-Revised (SCS-R) at baseline and 2 weeks after the psilocybin session. A significant between-group difference was observed in change in nature relatedness pre-to-postpsilocybin session [χ2(1) = 5.74, p = 0.02]. Nature relatedness significantly increased in the visual healing group [median change in NR-6 = 0.33, range = (-0.17, 0.67), p = 0.01], but not in the standard setting group [median change = 0.00; range = (-0.17, 0.33), p = 0.50]. No significant between-group differences were observed for change in social connectedness [χ2(1) = 0.89, p = 0.35], and no significant overall change in social connectedness was observed across groups [median change = -1.00, range = (-27, 20), p = 0.90]. Viewing a nature-themed video may enhance nature relatedness among individuals undergoing psilocybin-assisted psychotherapy for AUD. Future research should investigate the effects of real-life nature immersion and explore nature relatedness and other forms of connectedness as potential therapeutic targets in psychedelic-assisted and other psychotherapies NCT04410913.

Rich R
Laird K
Siddarth P
Youssef B
Schwartz GM
Ramos A
Sergi K
Linton M
Schwartzberg L
Kelly DF
Heinzerling KG


Regulation of α-bergamotene biosynthesis by the LcDOF5.8-LcTPSbms regulatory module in litchi fruit

Abstract: Bergamotene, a key sesquiterpene compound, is crucial for defining the fruity aroma. However, the precise regulatory mechanisms governing its biosynthesis have been largely elusive. In this study, we elucidated that the DOF transcription factor LcDOF5.8 plays a central role in the biosynthesis of α-bergamotene by directly enhancing the expression of the terpene synthase gene LcTPSbms in litchi fruit. Our findings revealed that the concentration of α-bergamotene varies significantly among four distinct litchi cultivars: 'Guanyinlv', 'Bingli', 'Guiwei' and 'Nuomici'. Notably, a strong correlation was observed between the expression level of LcTPSbms and the content level of α-bergamotene across these cultivars. Furthermore, both in vitro and in vivo catalytic assays confirmed that LcTPSbms is capable of catalyzing the synthesis of α-bergamotene. Importantly, electrophoretic mobility shift assays (EMSA) and Dual-LUC assays demonstrated that LcTPSbms is positively regulated by LcDOF5.8. Silencing LcDOF5.8 in litchi aril resulted in decreased LcTPSbms expression, whereas transient overexpression of LcDOF5.8 led to a significant upregulation of LcTPSbms and a concomitant increase in α-bergamotene biosynthesis. In summary, our research uncovers a regulatory module involving LcDOF5.8 and LcTPSbms that plays a critical role in the biosynthesis of α-bergamotene, offering valuable insights into the molecular mechanisms underlying the fruity aroma of litchi fruit.

Wang Y
Liu Z
Wang M
Qian D
Ma K
Zhao M
Li J
Ma X


Predicting Nurses' Views on Decriminalization of Psychedelics

Abstract: Despite being the largest sector of the health care workforce with potential to support advancing psychedelics in health care, nurses and their views toward psychedelics and changing legal restrictions remain mostly unknown. To identify an optimal predictive model for nurses' support (or not) of decriminalization of psychedelics. Secondary analysis of e-survey data from 1092 registered nurses and advanced practice registered nurses invited randomly from the Minnesota Board of Nursing registry. To develop an optimal predictive model, multinomial logistic regression with backward selection using the Akaike information criterion (AIC) was applied to the training set. The final model was fitted to the validation set for effect estimation, with performance assessed using multiclass area under the curve (AUC). Backward selection using AIC identified several key predictors of support for decriminalization of psychedelics in Minnesota: age, gender identity, specific spiritual orientation, awareness of Colorado's psychedelic decriminalization, and scores from the Attitudes and Perceptions Questionnaire legal and effects subscales. The final model demonstrated excellent discriminative ability with a multiclass AUC of 0.870 (95% confidence interval [CI]: 0.847-0.898). Pairwise comparisons revealed outstanding discrimination between supporters and opponents of decriminalization (AUC = 0.973, 95% CI: 0.952-0.987). Age (younger/older), (awareness/lack of awareness) of Colorado's decriminalization laws, and attitudes (concerns/lack of concerns) toward effects and legal status of psychedelics predicted a nurse's (more/less positive) attitude toward psychedelics. This model offers an informative starting point for understanding nurses' and, by proxy, the communities in which they live and work and provides initial direction toward tailoring curricular and professional development resources on psychedelics for nurses across the United States.

Porta CM
Wu CC
Graefe A
Grumdahl N
Dorsen C


Identifying ROCK2 as an intervention target for bilirubin encephalopathy

Abstract: Neonatal bilirubin encephalopathy is primarily characterized by central auditory dysfunction and cognitive impairments. However, the precise molecular mechanisms underlying bilirubin-induced neurotoxicity remain poorly understood, hindering the development of effective therapeutic strategies. Using kinase activity prediction tools based on quantitative phosphoproteomics, we identified ROCK2 (Rho-associated protein kinase 2) as a critical kinase regulating the phosphorylation of proteins associated with bilirubin exposure. Molecular docking and MicroScale Thermophoresis assays revealed a strong binding affinity between bilirubin and ROCK2. Interestingly, bilirubin increased ROCK2 protein expression without affecting its mRNA levels, and cycloheximide chase assays revealed enhanced ROCK2 stability, implicating post-translational regulation. While bilirubin did not directly activate ROCK2 kinase activity in vitro, it elevated phosphorylation of its substrate LIMK1, suggesting that ROCK2 accumulation amplifies downstream signaling. In primary rat neurons, ROCK2 inhibitors (Belumosudil and Y-27632) ameliorated bilirubin-induced loss of mitochondrial membrane potential and neuronal cell death. Furthermore, using ROCK2 inhibitors and Rock2+/- mice, we demonstrated that modulation of ROCK2 significantly alleviated bilirubin-induced auditory deficits and cognitive impairments. These behavioral improvements were linked to restored excitatory synaptic transmission in the cochlear nucleus and reduced dendritic damage in hippocampal neurons. These findings position ROCK2 as a promising molecular target for therapeutic intervention in bilirubin encephalopathy.

Ke B
Mao L
Hu M
Cui Y
Chen M
Wu C
Guan R
Yin S
Li C


Photonic biosensors based on nanoparticle superstructures: from data analysis to artificial intelligence (AI) detection

Abstract: The superstructures formed by the self-assembly of nanoparticles (NPs) can exhibit unique photonic collective properties (structural color, localized surface plasmon resonance [LSPR]), enhance the interaction between light and matter, and open up new possibilities for photonic sensing. Many photonic biosensors have addressed the limitations of current bioanalytical methods with their non-invasive nature, real-time monitoring, and high sensitivity. In recent years, the construction of photonic biosensors using super-structured materials could further enhance the sensors in terms of sensitivity, processing capacity, ease of use, and miniaturization. Superstructure-based photonic biosensors can analyze complex samples, but their development still needs to overcome limitations related to target binding specificity, long-term stability, and signal decoding efficiency. The development of artificial intelligence (AI) provides new opportunities to solve these problems. Deep learning (DL) algorithms can independently extract multi-dimensional data features such as spectra and images, distinguish weak biological signals from noise, optimize detection parameters, and achieve real-time dynamic calibration. In this review, we provide the photonic collective characteristics of superstructures and the applications of biosensors in intelligent diagnosis. The applications of superstructured photonic sensors in disease diagnosis, drug delivery, and cell imaging are summarized. The colorimetric, fluorescence-based sensor technologies assisted by DL are discussed along with challenges faced in integrating AI with superstructure-based photonic biosensors. As this field continues to evolve, the integration of AI and superstructure-based photonic biosensors will undoubtedly play a pivotal role in shaping the future of medical diagnostics and therapeutic interventions.


Assessing The Readiness of Psychiatrists in Louisiana to Incorporate Psilocybin into Clinical Practice-Lessons Learned from a State Underrepresented in Clinical Psychedelic Research

Abstract: Psilocybin has been granted breakthrough therapy status in the United States, speeding its advancement from research to clinical care. Due to the controversial nature of psilocybin, psychiatrists may not be fully prepared to incorporate it into clinical practice. The current study aimed to evaluate the opinions toward psilocybin among practicing psychiatrists in Louisiana. Louisiana serves as a representative state, modeling other areas with limited exposure to psychedelic research. A 30-question survey was distributed via mail and digital newsletter to all registered Louisiana psychiatrists. The survey consisted of demographic questions and questions pertaining to how strongly respondents agreed or disagreed with statements about psilocybin and psychedelics on a five-point Likert scale. The statements aimed to assess knowledge and exposure to psilocybin including opinions on research and legalization, safety and addiction potential, medical use, and potential benefits and usages. Forty-nine responses were recorded. Eighty-two percent of participants reported having "some knowledge" of psilocybin. Eighty-six percent believed psilocybin should be researched for medicinal value, and 71% would prescribe psilocybin if it were proven beneficial for their patient's illness. Fifty-seven percent believed it should be considered a first-line treatment for certain conditions, while 73% believed it should be used only after exhausting all other treatment modalities. The study had an overall 10.5% response rate, potentially limiting the generalizability of the findings. Louisiana psychiatrists in our sample appear open to integrating psilocybin into their practice if there is strong regulatory support. Psilocybin research is rapidly expanding and will soon reach Louisiana and other states with a limited history of psychedelic clinical research. These findings warrant the development of an educational program on psychedelics to arm psychiatrists and patients with the knowledge to make the most informed decisions.

Husein A
Traylor M
Vest MF
Wood BJ
Brogan M
Thomas A
McNeil S
Bhuiyan MAN
Hendricks P
Kelly JR
Gribben A
Al-Qahtani MM
Keys K
Edinoff AN
Patterson JC
Murnane KS


Reply to: Radiographic Progression With and Without Prostate-Specific Antigen Rise in Patients With Advanced Prostate Cancer Treated With Enzalutamide

Journal of clinical oncology : official journal of the American Society of Clinical Oncology

Armstrong AJ
Azad AA
Saad F
Hussain M
Iguchi T
Stenzl A
Sternberg CN