bluuebunny/crossref_metadata_2025 huggingface dataset:
Advancements in nutritional support for critically ill patients
Authors: Huynen Philippe , Casaer Michael P. , Gunst Jan
Published: February 2025

Purpose of review

To summarize the clinical evidence on nutritional support for critically ill patients, the (patho)physiological mechanisms involved, and areas of future research.

Recent findings

Large randomized controlled trials have shown that early nutrition induces dose-dependent harm in critically ill patients, regardless of the feeding route, and that early high-dose amino acids are harmful. Harm has been attributed to feeding-induced suppression of cellular repair pathways including autophagy and ketogenesis, to aggravation of hyperglycemia and insulin needs, and to increased urea cycle activity. Additionally, acute critical illness was shown to be a state of anabolic resistance. The absence of benefit of early enhanced nutritional support on short- and long-term outcomes was observed in all studied subgroups.

While early high-dose nutrition should be avoided in all critically ill patients, the optimal initiation time of nutrition support for the individual patient, as well as ideal composition and dosing of nutrition over time remain unclear. Future studies should elucidate how fasting-induced repair pathways can be activated while avoiding prolonged starvation, and how hyperglycemia and high insulin need could be prevented. Potential strategies include intermittent fasting, ketogenic diets, ketone supplements, and alternative glucose-lowering agents, whether or not in combination with exercise.
Study on the application effect of traditional Chinese medicine syndrome differentiation nursing in the rehabilitation of language function in patients with stroke
Authors: Lu JingTiao , Mi Jing , Zhou Jia
Published: February 2025

This study aimed to investigate the efficacy of traditional Chinese medicine (TCM) syndrome differentiation nursing in the rehabilitation of language function in stroke patients. This study compares the effects of TCM syndrome differentiation nursing and conventional rehabilitation nursing by assessing changes in language function using the Boston Diagnostic Aphasia Examination (BDAE) scores and clinical efficacy evaluation. This study is a retrospective study in which we reviewed cases of poststroke rehabilitation from 2020 to 2023. A total of 100 stroke patients were enrolled and divided into 2 groups: the TCM syndrome differentiation nursing group (n = 50) and the conventional rehabilitation nursing group (n = 50). TCM syndrome differentiation nursing was tailored based on individual patients’ TCM diagnoses (e.g., Qi deficiency, blood stasis, or phlegm-dampness) and involved a combination of targeted nursing care, acupuncture, and herbal remedies. The conventional rehabilitation nursing group received standard poststroke rehabilitation therapies, including speech therapy and physical exercises. Both groups were assessed using BDAE scores and clinical efficacy evaluations at baseline and after 12 weeks of intervention. The TCM syndrome differentiation nursing group showed significantly greater improvements in BDAE scores compared with the conventional rehabilitation group (mean increase: 15.2 vs 8.6, P < .05). In addition, 72% of patients in the TCM group were classified as having “marked improvement” in clinical efficacy, compared with 48% in the conventional rehabilitation group (P < .05). The TCM group also reported fewer complications such as fatigue and stress compared with the conventional rehabilitation group (P < .05). TCM syndrome differentiation nursing significantly enhances language function recovery in stroke patients and serves as a valuable supplement to conventional rehabilitation methods. This study provides novel evidence supporting the integration of TCM-based interventions in stroke rehabilitation, offering a complementary approach to existing therapeutic strategies. Further research is needed to explore the long-term effects and underlying mechanisms of TCM syndrome differentiation nursing.
Guillain-Barré syndrome during the COVID-19 era: A nationwide study of hospitalized cases in South Korea
Authors: Park Jin-Mo , Bae Jong-Sup
Published: February 2025

This study aimed to analyze the trends and characteristics of hospitalized Guillain-Barré syndrome (GBS) incidence and management in South Korea before and during the coronavirus disease 2019 pandemic, assessing potential impacts of nonpharmaceutical interventions and shifts in public health dynamics. We conducted a retrospective analysis using data from the Health Insurance Review and Assessment Service database from 2013 to 2021, divided into prepandemic (2013–2019) and pandemic (2020–2021) periods. Incident GBS cases were identified based on the G61.0 code with hospital admissions. A total of 10,596 hospitalized patients with GBS were identified, with 8537 cases in the prepandemic period and 2059 during the pandemic. While the overall GBS incidence did not show a statistically significant change during the pandemic (P = .056), the mean age of patients increased. Notably, a significant rise in the proportion of patients receiving intravenous immunoglobulin was observed during the pandemic (P < .001), with older patients showing higher mean ages (P = .007). However, the proportion of patients requiring mechanical ventilation remained stable (P = .240). The findings suggest that while hospitalized GBS incidence remained stable amidst the pandemic and reduced respiratory infection admissions, the increase in intravenous immunoglobulin use points to more severe presentations, particularly among older patients. This highlights the multifactorial nature of GBS triggers and the need for continued investigation into how evolving public health measures and infectious disease patterns influence GBS incidence and management.
SMARCA4-deficient Non–small Cell Lung Cancer on 18F-FDG PET/CT
Authors: Liu Tao , Ji Hengshan , Jiang Siyuan , Qi Rongxin , Zhou Xiaodie , Sun Jingjing , Wu Jiang
Published: February 2025

A 70-year-old man, a heavy smoker, presented with multiple lesions in both lungs during a computed tomography check-up. The largest nodule in the upper lobe of the right lung indicated a high malignancy risk. Subsequent positron emission tomography/computed tomography showed the largest nodule with a high avidity of 18F-FDG (SUVmax: 5.59). Curative surgery removed the nodule, and pathologic examination confirmed that the nodule was SMARCA4-deficient non–small cell lung cancer.
99mTc-PSMA Scintigraphy of Subcutaneous Angiolipoma
Authors: Saber Tanha Amin , Rafiei Zahra , Raeisi Nasrin , Tayyebi Meibodi Naser , Aghaee Atena
Published: February 2025

We present a case of a 69-year-old man diagnosed with prostate adenocarcinoma, who underwent 99mTc-PSMA scintigraphy as part of his initial staging workup. The scan revealed a focal uptake in the posterior abdominal wall, corresponding to a subcutaneous soft tissue lesion. Further evaluation using SPECT/CT imaging localized the lesion, which was subsequently excised and histopathologically diagnosed as an angiolipoma. This case represents the first reported instance of PSMA-based detection of angiolipoma as a false-positive finding using 99mTc-PSMA scintigraphy.
Cell-penetrating peptide-mediated mouse oocyte activation
Authors: Suzuki Toru
Published: February 2025

Introduction

The cell cycle of ovulated oocytes from various animal species, including mice, is arrested in the second meiotic metaphase until fertilization. The meiotic cell cycle must be initiated to initiate embryonic development. Besides natural fertilization, several other methods have been developed to activate unfertilized oocytes without using sperm. These methods are not only utilized for animal production but have also proven effective in studying the molecular mechanisms that regulate the meiotic cell cycle, oocyte activation, and embryonic development. This study aimed to develop a method to activate mouse oocytes using a cell-penetrating peptide based on the knowledge that the C-terminal domain of the meiotic protein Emi2 can resume the arrested meiotic cell cycle.

Methods

This study used female B6D2F1 mice to investigate the effects of a CPP-fused Emi2 peptide on oocyte activation. Second meiotic metaphase oocytes were collected, cultured, and treated with the peptide or strontium chloride. Pronuclear formation, second polar body extrusion, and blastocyst development were assessed, and statistical significance was determined using Fisher’s exact test.

Results

The cell-penetrating peptide activated zona-intact oocytes in a manner dependent on specific amino acid residues and peptide concentrations, which are critical components for cell membrane penetration. It has also been confirmed that oocytes activated using this method can develop to the blastocyst stage.

Discussion

The introduction of peptides or functional amino acid sequences using CPP or related methods could be an alternative for easily performing functional analyses of the activity of target proteins in oocytes.
A MULTI-MINERAL INTERVENTION TO IMPROVE DISEASE-RELATED AND MECHANISTIC BIOMARKERS IN ULCERATIVE COLITIS PATIENTS
Authors: Aslam Muhammad N. , Turgeon Danielle (Kim) , Appelman Henry D. , Stidham Ryan , McClintock Shannon , Allen Ron , Moraga Gillian , Harber Isabelle , Jencks Kara J. , McNeely Molly M. , Sen Ananda , Jepsen Karl J. , Varani James
Published: February 2025

Introduction

The long-term goal of our studies is to determine if, and to what extent, a multi-mineral product (Aquamin) could have beneficial impact on individuals with ulcerative colitis (UC). As a step toward achieving that goal, we carried out a 180-day biomarker trial in patients with UC in remission or at the mild stage.

Approach

A total of 28 subjects were included in the study. Each was randomized to receive either Aquamin for 180 days or placebo for the first 90 days. At day-90, placebo subjects crossed over to Aquamin for the final 90 days. At days-0, −90 and −180, serum samples were assessed for alkaline phosphatase (ALP), intestine-specific ALP (ALPI), C-reactive protein (CRP) and for biomarkers of bone turnover (osteocalcin, TRAP5b and bone-specific ALP [e.g., BALP]). Stool specimens were assessed for fecal calprotectin at the same time points and colon biopsies were examined histologically. Each subject underwent DEXA scanning (day-0 and −180 only). In addition, a mass spectrometry-based proteomic assessment was performed using colon biopsy specimens obtained at each time point.

Results

Subjects receiving Aquamin for the complete 180-day period (a total of 12) demonstrated improvement in all biomarkers; this was not seen in the placebo group (16 subjects). Subjects who received Aquamin for 90-days were intermediary in their responses. Subjects receiving Aquamin for 180-days also demonstrated increases in bone mineral density (BMD) and bone mineral content (BMC) resulting in a statistically-significant increase in the hip strength index over the period of treatment. This was accompanied by increases in osteocalcin and TRAP5b and by a decrease in BALP. The proteomic screen demonstrated up-regulation of multiple gut barrier proteins, cell surface transporter molecules and certain proteins with anti-inflammatory potential in response to Aquamin. Aquamin treatment also led to down-regulation of several proteins associated with the pro-inflammatory state.

Conclusion

These findings suggest the potential value of multi-mineral intervention (Aquamin) as a low-cost, non-toxic adjuvant therapy for mild UC or for individuals with UC in remission.
The Austrian MS Database and the Austrian MS Cohort – a national effort towards data harmonization and prospective data collection
Authors: Bsteh Gabriel , Föttinger Fabian , Ponleitner Markus , Berek Klaus , Di Pauli Franziska , Heschl Bettina , Wurth Sebastian , Deisenhammer Florian , Enzinger Christian , Berger Thomas , Khalil Michael , Hegen Harald ,   the Austrian Multiple Sclerosis Database and Austrian MS cohort study group
Published: February 2025

Background

A variety of disease-modifying therapies (DMTs) are now available for multiple sclerosis (MS), each with distinct efficacy and risk profiles. However, the clinical course of MS varies significantly both within and between individuals, and the optimal treatment strategy remains uncertain at the group and individual levels. Addressing questions about treatment strategies through traditional randomized controlled trials is unrealistic due to the large sample sizes and high costs required. Instead, large-scale multicenter registries and well-characterized prospective observational cohorts offer a feasible approach to generating meaningful insights. For valid results, such registries and cohorts require harmonization across centers to support comprehensive, standardized, user-friendly data collection while meeting data protection standards and ensuring quality control.

Objective

This project aims to establish standardized, nationwide MS data collection in Austria.

Methods

The project consists of five key components: i) harmonization of data collection, ii) creation of infrastructure for data sharing, iii) retrospective harmonized data collection (Austrian MS Database, AMSD), iv) prospective harmonized data collection (Austrian MS Cohort, AMSC), and v) aggregated analyses.

Results

A comprehensive set of harmonized common data elements (CDE) comprising clinical and paraclinical data was developed and a common data collection infrastructure was generated using the web-based Research, Documentation, and Analysis platform (webRDA), an innovative data capture, processing, and analysis system provided by the Medical University of Vienna offering pseudonymized storage of data supported by a robust permissions system sufficing legal data protection and ethical requirements.

The AMSC is set up as a standardized prospective collection of demographic, clinical, epidemiological, psycho-socio-economic, MRI, and OCT data as well as body fluids.

Conclusion

The AMSD and AMSC will facilitate the evidence-based development of prognostic biomarkers, individualized therapy strategies and treatment sequences based on a high-quality, population-based dataset of more than 8,000 people with MS.
Rare gain-of-function regulatory mutations explain the missing heritability of bicuspid aortic valve
Authors: Zhigulev Artemy , Petersson Sjögren Madeleine , Buyan Andrey , Nozdrin Vladimir , Lázár Enikő , Mauron Raphaël , Lång Karin , Spalinskas Rapolas , Schwochow Doreen , Pradhananga Sailendra , Franco-Cereceda Anders , Lundeberg Joakim , Kulakovskiy Ivan V. , Eriksson Per , Björck Hanna M , Sahlén Pelin
Published: February 2025

Bicuspid aortic valve (BAV), a prevalent congenital cardiac defect, predisposes patients to severe complications. Despite its high heritability, previously identified protein-coding and common regulatory mutations account for only a small fraction of cases. To address this gap, we investigated the role of rare regulatory mutations. By integrating high-resolution three-dimensional genome organization profiling with whole-genome sequencing, we analyzed sixteen patients with BAV and normal tricuspid aortic valves. Our findings reveal a 1.5-fold enrichment of gain-of-function regulatory mutations in previously implicated genes among BAV patients. Genome-wide, moderately rare mutations (allele frequencies below 3%) were predicted to alter the transcriptome of specific developmental valve mesenchymal cell and fibroblast populations. Expanding the BAV pathway network with newly implicated genes uncovered substantial genetic heterogeneity underlying the disease. These results position rare regulatory mutations as pivotal contributors to missing BAV heritability and emphasize the need for further research of their mechanistic roles.
Kupffer cells control neonatal hepatic metabolism via Igf1 signaling
Authors: Makdissi Nikola , Hirschmann Daria , Frolov Aleksej , Sado Inaam , Nikolka Fabian , Cheng Jingyuan , Blank-Stein Nelli , Viola Maria Francesca , Yaghmour Mohamed , Arnold Philipp , Bonaguro Lorenzo , Becker Matthias , Thiele Christoph , Meissner Felix , Hiller Karsten , Beyer Marc D. , Mass Elvira
Published: February 2025

During perinatal development, liver metabolism is tightly regulated to ensure energy supply for the newborn. Before birth, glycogen is stored in hepatocytes and later metabolized to glucose, meeting the energy demands of the neonate. Shortly after birth, lipogenesis begins, driven by the transcriptional activation of enzymes involved in fatty acid oxidation. These processes are thought to be largely regulated by systemic insulin and glucagon levels. However, the role of liver-derived local factors in neonatal hepatocyte metabolism remains unexplored. Kupffer cells (KCs), the liver’s resident macrophages, colonize the fetal liver early in embryogenesis and support liver metabolism in adulthood. Yet, whether KCs influence neonatal hepatocyte metabolism is unknown. Here, using conditional knockout mouse models targeting macrophages, we demonstrate that yolk sac-derived KCs play a critical role in hepatocyte glycogen storage and function by regulating the tricarboxylic acid (TCA) cycle - a role that monocyte-derived KC-like cells cannot substitute. Newborn pups lacking yolk sac-derived KCs mobilize glycogen more rapidly, a process regulated by insulin-like growth factor 1 (Igf1) production. Our findings reveal that macrophages are a major source of Igf1 at birth and that local Igf1 production by KCs is essential for balanced hepatocyte metabolism.
AFD Thermosensory Neurons Mediate Tactile-Dependent Locomotion Modulation inC. elegans
Authors: Rosero Manuel , Bai Jihong
Published: February 2025

Sensory neurons drive animal behaviors by detecting environmental stimuli and relaying information to downstream circuits. Beyond their primary roles in sensing, these neurons often form additional synaptic connections outside their main sensory modality, suggesting broader contributions to behavior modulation. Here, we uncover an unexpected role for the thermosensory neuron AFD in coupling tactile experience to locomotion modulation inCaenorhabditis elegans. We show that while AFD employs cGMP signaling for both thermotaxis and tactile-dependent modulation, the specific molecular components of the cGMP pathway differ between these two processes. Interestingly, disrupting the dendritic sensory apparatus of AFD, which is essential for thermotaxis, does not impair tactile-based locomotion modulation, indicating that AFD can mediate tactile-dependent behavior independently of its thermosensory apparatus. In contrast, ablating the AFD neuron eliminates tactile-dependent modulation, pointing to an essential role for AFD itself, rather than its sensory dendritic endings. Further, we find tactile-dependent modulation requires the AIB interneuron, which connects AFD to touch circuits via electrical synapses. Removing innexins expressed in AFD and AIB abolishes this modulation, while re-establishing AFD-AIB connections with engineered electrical synapses restores it. Collectively, these findings uncover a previously unrecognized function of AFD beyond thermosensation, highlighting its influence on context-dependent neuroplasticity and behavioral modulation through broader circuit connectivity.
Mapping the Landscape of Allele-Specific Expression In Porcine Genomes
Authors: Yao Wen-ye , Gòdia Marta , Fang Lingzhao , Groenen Martien A. M. , Bai Lijing , Li Kui , Madsen Ole
Published: February 2025

Allele-specific expression (ASE) is the imbalanced expression of two alleles of the same locus. It is quite pervasive among mammals and is associated with healthy and economically relevant traits. ASE is often used to support the identification of variants related to gene expression (cis-eQTLs). Thus, profiling ASE represents a significant step in elucidating the mechanism underlying gene expression regulation. In this study, we developed an ASE pipeline using public available RNA-seq data and open-source software. Using this pipeline, we were able to profile pervasive allelic imbalance across 42 tissues and 34 breeds from the Farm-GTEX-pig consortium at both SNP and gene levels without the need for parental genotype or whole genome sequence data. ASE was widely, but not evenly, spread across the genome. We also observed considerable variation in ASE profiles among various tissues, in which the ASE fraction ranged from 1.3% to 54.1%. ASE tends to be highly tissue-specific, and the overlap across tissues is limited. The functional analysis of tissue-specific ASE sites indicates that they are involved in the critical maintenance of these tissues. Our ASE pipeline can be readily applied to other RNA-seq data sets for livestock, thereby significantly expanding its potential utility. The wealth of available ASE resources provides a solid foundation for identifying regulatory elements within the genome that drive complex traits in livestock, making our pipeline and results valuable resources for researchers in this field.
Altered mechanical properties of astrocytes lacking MLC1; implications for the leukodystrophy MLC
Authors: Bisseling Quinty , Passchier Emma M.J. , Antonovaite Nelda , Camerini Serena , Brignone Maria S. , Freal Amélie , Mansvelder Huibert D. , Ambrosini Elena , van der Knaap Marjo S. , Min Rogier
Published: February 2025

Loss of function of the astrocyte protein MLC1 causes Megalencephalic Leukoencephalopathy with subcortical Cysts (MLC), a leukodystrophy characterized by white matter edema and slow neurological deterioration. MLC1 dysfunction leads to swelling of perivascular astrocyte endfeet and an impaired attachment of endfeet to blood vessels. In isolated primary astrocytes, loss of MLC1 hinders recovery of astrocytes from cell swelling, but the cellular function of MLC1 is not completely understood. MLC1 modulates gating of mechanosensitive ion channels involved in volume regulation. The cytoskeleton plays a crucial role in cell volume regulation, and interactions between the cytoskeleton and cell membrane affect the properties of mechanosensitive ion channels. Therefore, we investigated whether primaryMlc1-null mouse astrocytes show a disruption in their mechanical properties. We measured mechanical properties of cultured primary astrocytes with an indentation technique and demonstrated thatMlc1-null astrocytes are softer than wild-type astrocytes. Proteomic analysis confirmed dysregulation of several cytoskeleton-related pathways inMlc1-null astrocytes. Confocal imaging revealed that organization of the actin cytoskeleton is unaffected. Instead, we observed alterations in focal adhesions, which aid in relaying mechanical forces between the cytoskeleton, cell membrane, and the extracellular matrix (ECM). Together, our findings reveal that the mechanical properties ofMlc1-null astrocytes are altered, and that disrupted cytoskeleton-membrane-ECM interactions potentially play a role in the disease. Modulators of astrocyte mechanobiology might therefore hold promise for MLC therapy development.
A discrete region of the D4Z4 is sufficient to initiate epigenetic silencing
Authors: Paatela Ellen M. , St. Amant Faith G. , Hamm Danielle C. , Bennett Sean R. , Gujral Taranjit S. , van der Maarel Silvère M. , Tapscott Stephen J.
Published: February 2025

The DUX4 transcription factor is briefly expressed in the early embryo and is epigenetically repressed in somatic tissues. Loss of epigenetic repression can result in the aberrant expression of DUX4 in skeletal muscle and can cause facioscapulohumeral dystrophy (FSHD). Multiple factors have been identified as necessary to maintain epigenetic silencing ofDUX4in skeletal muscle, but whether specific sequences at theDUX4locus are sufficient for epigenetic silencing has been unknown. We cloned fragments of the D4Z4 macrosatellite repeat, the DNA region that encompasses theDUX4retrogene, adjacent to a reporter driven by a constitutive promoter and identified a single fragment sufficient to epigenetically repress reporter gene expression. Previously identified suppressors ofDUX4expression—SETDB1, ATF7IP, SIN3A/B, and LRIF1—were necessary for silencing activity and p38 inhibitors enhanced suppression. These findings identify a key regulatory sequence for D4Z4 epigenetic repression and establish a model system for mechanistic and discovery studies.
3D spatial transcriptomics reveals the molecular domain structure of the mouse olfactory bulb
Authors: Klimpert Nell , Kollo Mihaly , Brann David H. , Tan Chichun , Barry David , Ma Ying , Schaefer Andreas T. , Fleischmann Alexander
Published: February 2025

A core organizing principle of the vertebrate brain is its symmetry along multiple axes. However, the structure of these axes, and the precision with which neurons, circuit modules, and brain regions align to them, remain poorly understood. Here, we used 3D spatial transcriptomics to reconstruct the anatomical and molecular organization of the mouse olfactory bulb. We mapped the positions of nearly one thousand molecularly distinct glomeruli, the structural and functional units of odor processing, revealing highly symmetric organization across brain hemispheres. Within each bulb, we defined a curved axis of symmetry that divides pairs of sister glomeruli. Gene expression programs in olfactory sensory neurons predicted glomerular position with near-glomerular resolution. However, glomerular symmetry was disrupted in deeper layer mitral and granule cells, suggesting a reorganization of olfactory bulb output pathways. Our findings provide the first comprehensive map of the molecular domain structure of the olfactory bulb.
Sensory Cues in Assistive Technologies: a Comparative Study of the BuzzClip and NOA
Authors: Pittet Claire E. , Fabien Maël
Published: February 2025

Electronic travel aids have the potential to significantly improve the security and independence of blind or visually impaired people when traveling. However, it is critical that such devices convey relevant information without overwhelming users. This study examines the performance of two assistive technologies in obstacle detection: the BuzzClip, which uses ultrasonic sensors to provide haptic feedback, and NOA, which utilizes infrared cameras and an AI-powered computer to deliver audio feedback. One participant completed four different mobility routes with each route tested separately using both devices, and the number of auditory or haptic stimuli was recorded. According to the data collected, the BuzzClip produced significantly more sensory feedback than NOA. This difference can be attributed to the devices’ detection methods and the ability to filter obstacles. These findings highlight the differences between certain electronic travel aids, underlining the importance of creating tools that provide sufficient information to users while avoiding the potential sensory overload caused by excessive stimuli. Such considerations are crucial in designing mobility tools that effectively enhance mobility while offering an agreeable experience for users.
Food Deserts and Food Insecurity in Indian Medical Colleges: A Mixed Methods Study Exploring Myths and Realities
Authors: Joykutty Mekha , Reshma V. R , John Anjum
Published: February 2025

Introduction

Lack of consistent access to sufficient, nutritious food is a pressing issue globally. Resilient food systems amalgamating multiple sectors like agriculture, animal husbandry, healthcare, and education are essential to resolve food insecurity. College students, particularly in medical colleges, are vulnerable to food insecurity due to limited access to healthy food, lack of resources (time, money, and knowledge), resulting in unhealthy eating habits. This study aims to investigate the presence of food deserts within medical colleges in Kerala, analyze factors influencing student food preferences, and explore the consequences of food insecurity on their health and academic performance.

Methods and Analysis

A cross-sectional study will be conducted at a private medical college in Central Kerala over 8 months. Food outlets within a one-mile radius of the campus will be identified and assessed for affordability, variety, and nutritional quality. Data will be collected from medical students (medical, dental, nursing, laboratory) throughout all years using structured questionnaires, focus group discussions, and interviews with food outlet operators. Stratified random sampling will ensure representation across different academic years, and disciplines. Observations of food outlets will evaluate food variety, pricing, and hygiene standards. Quantitative data will be analyzed using descriptive and inferential statistics, while qualitative data will be thematically analyzed to gain deeper insights.

Ethics and Dissemination

Ethical approval has been obtained, and informed consent will be collected from participants. Data confidentiality will be strictly maintained. Findings will be disseminated through academic conferences, publications, and policy briefs using de-identified data to advocate for healthier food environments on campuses.

Key Messages

Food insecurity among medical college students is a relatively under-researched issue, particularly in India, with limited studies on food deserts in such settings.

This study identifies food deserts around a private medical college in Kerala and examines how limited access to nutritious food affects students’ health and academic performance.

Through a mixed-methods design, combining quantitative surveys and qualitative focus group discussions, it provides a comprehensive understanding of the food environment, including the affordability and quality of food outlets.

The findings highlight the need for policy interventions to improve food access and quality on campuses and suggest this research could guide future studies and influence public health and campus food policies.

While this study is groundbreaking for the region, its findings may be limited in generalizability to other institutions or regio
Persons with multiple sclerosis reveal distinct kynurenine pathway metabolite patterns: a multinational cross-sectional study
Authors: Kupjetz M. , Langeskov-Christensen M. , Riemenschneider M. , Inerle S. , Ligges U. , Gaemelke T. , Patt N. , Bansi J. , Gonzenbach R. , Reuter M. , Rosenberger F. , Meyer T. , McCann A. , Ueland P.M. , Eskildsen S.F. , Nygaard M.K.E. , Joisten N. , Hvid L.G. , Dalgas U. , Zimmer P.
Published: February 2025

Neuroaxonal damage in multiple sclerosis (MS) results from an interplay of neurotoxic pathomechanisms combined with a reduced neuroprotective capacity of neurons and glia to resist neurotoxic damage. Kynurenine pathway (KP) imbalance resembles some of the molecular mechanisms central to the incompletely understood MS pathophysiology. To study the role of the KP in MS, we performed targeted metabolomics on serum samples from 353 persons with MS and 111 healthy individuals, and detected MS-specific differences in concentrations of most kynurenines. Using exploratory factor analysis, we then identified two distinct KP metabolite patterns: the inflammation-driven neurotoxic pattern „NeuroTox“ and the neuroprotective pattern „NeuroPro“. Our results show that greater „NeuroTox“ and lower „NeuroPro“ were associated with higher disease severity. The novelty of our data-driven approach that identified distinct KP metabolite patterns in MS advocates for future studies using comparable approaches to investigate whether KP imbalance follows similar disease-specific patterns in diseases other than MS.
Comparison of Large Language Models’ Performance on Neurosurgical Board Examination Questions
Authors: Andrade Nicholas S. , Donty Surya
Published: February 2025

Background

Multiple-choice board examinations are a primary objective measure of competency in medicine. Large language models (LLMs) have demonstrated rapid improvements in performance on medical board examinations in the past two years. We evaluated five leading LLMs on neurosurgical board exam questions.

Methods

We evaluated five LLMs (OpenAI o1, OpenEvidence, Claude 3.5 Sonnet, Gemini 2.0, and xAI Grok2) on 500 multiple-choice questions from the Self-Assessment in Neurological Surgery (SANS) American Board of Neurological Surgery (ABNS) Primary Board Examination Review. Performance was analyzed across 12 subspecialty categories and compared to established passing thresholds.

Results

All models exceeded the threshold for passing, with OpenAI o1 achieving the highest accuracy (87.6%), followed by OpenEvidence (84.2%), Claude 3.5 Sonnet (83.2%), Gemini 2.0 (81.0%) and xAI Grok2 (79.0%). Performance was strongest in Other General (97.4%) and Peripheral Nerve (97.1%) categories, while Neuroradiology showed the lowest accuracy (57.4%) across all models.

Conclusions

State of the art LLMs continue to improve, and all models demonstrated strong performance on neurosurgical board examination questions. Medical image analysis continues to be a limitation of current LLMs. The current level of LLM performance challenges the relevance of written board examinations in trainee evaluation and suggests that LLMs are ready for implementation in clinical medicine and medical education.
Mapping functional hemodynamic and metabolic responses to dementia: a broadband spectroscopy pilot study
Authors: Acharya Deepshikha , Butters Emilia , Caicedo Alexander , Su Li , O’Brien John , Bale Gemma
Published: February 2025

Significance

Broadband near-infrared spectroscopy (bNIRS) can simultaneously monitor several chromophores including the oxidative state of cytochrome c-oxidase (oxCCO), an oxygen metabolism biomarker whose activity is altered in Alzheimer’s disease. Being a portable and non-invasive neuromonitoring technique, bNIRS could thus provide accessibility to brain-specific biomarkers and aid in the dementia diagnostic pathway.

Aim

We use bNIRS recorded functional haemodynamic and oxCCO changes to assess their relevance in Alzheimer’s disease dementia as potential biomarkers.

Approach

Using a visual-stimulus paradigm, we recorded functional changes in oxy-, deoxy-haemoglobin and oxCCO in three similarly aged cohorts: healthy controls (n=5), individuals with mild cognitive impairment (n=7) and individuals with Alzheimer’s dementia (n=7). We then selected features from these functional responses to find the best correlation with clinical cognitive markers (cognitive and behavioural test scores and clinical diagnosis) using canonical correlation analysis.

Results

We found individual variations in peak amplitude and time-to-peak for all the stimulus-evoked bNIRS signals across the three cohorts. Canonical correlation analysis showed a strong correlation between bNIRS features and the clinical cognitive markers (r=0.902). However, repeating the same analysis by excluding the bNIRS oxCCO features leads to a significantly lower correlation (r=0.687) with the clinical markers.

Conclusions

oxCCO could be a crucial biomarker, partly explaining cognitive differences with dementia. bNIRS uniquely provides a portable and non-invasive technique to monitor several chromophores simultaneously including oxCCO with potential future applications in tracking dementia progression.
Filling the gap in the Neotropics: new firefly species provide insights into Central American biodiversity
Authors: Catalán Ana , Pérez Archila Claudia María , Echeverría Méndez Adriana María , Guitiérrez José Andrés , Monzón José , Badillo Viridiana Vega , Höhna Sebastian
Published: February 2025

Tropical ecosystems, particularly in the Neotropics, remain vastly understudied, especially regarding the biodiversity of many taxa such as fireflies. This study investigates the biodiversity and phylogenetic relationships of fireflies in Guatemala, focusing on the generaPhotinus, Photuris, andBicellonycha. Using genetic barcoding we generate time-calibrated phylogenetic trees, revealing deep divergent times between Guatemalan and North American fireflies and potentially multiple colonialization events. Using morphometric information, taxonomic keys and species delimitations models (mPTP) we identified four newPhotinusspecies:P. hunahpú, P. helodermensis, P. schusteri, andP. semetabajense. This work highlights the significant firefly biodiversity in Nuclear Central America and the potential for future species discovery. Biodiversity research is necessary for conservation efforts of key ecosystems and will broaden our understanding of general evolutionary processes.
Evaluation of Machine Learning and Traditional Statistical Models to Assess the Value of Stroke Genetic Liability for Prediction of Risk of Stroke within the UK Biobank
Authors: MacCarthy Gideon , Pazoki Raha
Published: February 2025

Background and objective

Stroke is one of the leading causes of mortality and long-term disability in adults over 18 years of age globally and its increasing incidence has become a global public health concern.

Accurate stroke prediction is highly valuable for early intervention and treatment. Previous studies have utilized statistical and machine learning techniques to develop stroke prediction models. Only a few have included genome-wide stroke genetic liability and evaluated its predictive values. This study aimed to assess the added predictive value of genetic liability in the prediction of the risk of stroke.

Materials and methods

The study included 243,339 participants of European ancestry. Stroke genetic liability was constructed using previously identified genetic variants associated with stroke by the MEGASTROKE project through genome-wide association studies (GWAS). In our study, we built four predictive models with and without stroke genetic liability in the training set: Cox proportional hazard (Coxph), Gradient boosting model (GBM), Decision tree (DT), and Random Forest (RF) to estimate time-to-event risk for stroke. We then assessed their performances in the testing set.

Results

Each unit (standard deviation) increase in genetic liability increases the risk of incident stroke by 7% (HR = 1.07, 95% CI = 1.02, 1.12, P-value = 0.0030). The risk of stroke was greater in the higher genetic liability group, demonstrated by a 14 % increased risk (HR = 1.14, 95% CI = 1.02, 1.27, P-value = 0.02) compared with the low genetic liability group. The Coxph model including genetic liability was the best-performing model for stroke prediction achieving an AUC of 69.54 (95% CI = 67.40, 71.68), NRI of 0.202 (95% CI = 0.12, 0.28; P-value = 0.000) and IDI of 1.0×10-04(95% CI = 0.000, 3.0×10-04; P-value = 0.13) compared with the Cox model without genetic liability.

Conclusion

Incorporating genetic factors in the model may provide a slight incremental value for stroke prediction beyond conventional risk factors.
Investigating the impact of sex and reproductive aging on latent signatures of modifiable dementia risk factors
Authors: Mukora Alice , Costantino Manuela , Parent Olivier , Devenyi Gabriel. A. , Chakravarty M. Mallar
Published: February 2025

Treating modifiable risk factors for dementia may serve to prevent maladaptive brain aging. These include, and are not limited to, obesity, hypertension, and other metabolic disorders. Nearly two-thirds of affected individuals are female, and emerging research has pointed to potential sex-specific factors, like reproductive aging, as potent modifiers of dementia risk. Here, we leverage neuroimaging to characterize sex differences in the neural signatures of modifiable dementia risk factors, examining their relationship with brain anatomy, and integrate female-specific factors related to menopause history in a sex-specific analysis. Using cross-sectional data from the UK Biobank, we selected a cohort of 31,711 (age 44-82, 55.2% female/44.8% male) participants without diagnosed neurological conditions and collated behavioral data previously determined as modifiable risk factors. Using Partial Least Squares Analysis (PLS), we examined latent signatures that represent linear combinations that maximize covariance between patterns of brain (mean cortical thickness from 64 regions) and risk factor variables. To examine sex differences, we performed PLS analysis using the entire sample. We performed linear models to explore age-by-sex interactions with the PLS-derived brain scores and the risk factor pattern scores. To examine sex-specific relationships, we performed separate PLS analyses for the males and females and integrated menopause-related variables into the latter analysis. Our study found sex-dependent and menopause-dependent relationships between lifestyle risk factors and cortical thickness, highlighting stronger impacts of cardiometabolic factors on males and social and obesity-related factors on females in preserving brain health. The inclusion of menopause-related variables did not change the relationships to lifestyle risk factors, and strict age-matching dampened the strength of the findings. Our findings suggest that lifestyles and the female-specific endocrine environment influence sex differences in cortical anatomy during brain aging.
Asengeprast, a Novel G-Protein Coupled Receptor 68 Antagonist, Reverses Clinically Relevant Inflammatory and Fibrotic Pathways in Chronic Kidney Disease
Authors: Eddy Sean , Papadimitriou Michelle P. , Edgley Amanda J. , Langham Robyn G. , Khong Fay L. , Kong Roy C.K. , Carbone Simona E. , Kompa Andrew R. , Zhang Yuan , Cox Alison , Mitchell Lorna , Subramanian Lalita , Martini Sebastian , Hartman John , Eichinger Felix , Godfrey Bradley , Mariani Laura H. , Kretzler Matthias , Kelly Darren J. ,   Nephrotic Syndrome Study Network (NEPTUNE)
Published: February 2025

Abstract

Limiting progressive fibrosis in chronic kidney disease (CKD) is an ongoing therapeutic challenge that requires effective and safe inhibition of a broad inflammatory cell milieu that leads to irreversible organ damage. Asengeprast, an anti-fibrotic and anti-inflammatory small molecule, has shown promising efficacy in animal models of kidney disease, however its target and mechanism of action was unknown. Using in vitro assays, we showed that asengeprast modulates inflammatory and fibrotic responses through selective inhibition of G protein-coupled receptor 68 (GPR68), a proton sensor, expressed in tissue-resident and immune-infiltrating cells of the kidney. Transcriptomic analysis of kidney tissue from animal models of diabetic kidney disease (DKD) and CKD demonstrated that fibrotic and inflammatory pathways dysregulated in disease were reversed by asengeprast treatment. Differential expression analysis of upstream regulators showed that the major, distinct signaling networks reversed were centered on a key driver of fibroblast activation, transforming growth factor β1, and associated signaling molecules. An asengeprast response gene signature derived from the CKD animal model when mapped onto gene expression profiles obtained from human kidney biopsies confirmed that the molecular pathways modulated by asengeprast were also dysregulated in human DKD and CKD. Further, this asengeprast response signature correlated with clinical markers of disease progression and tissue pathology. Overall, these findings provide evidence for targeted inhibition of GPR68 by asengeprast as a promising therapeutic strategy for treatment of CKD and potentially other fibrotic and inflammatory conditions.

Translational Statement

Existing therapeutic strategies for chronic kidney disease (CKD) do not directly target both inflammatory and fibrotic processes needed to slow or halt the progression of disease.

Asengeprast is a Phase II candidate drug for CKD that blocks G protein-coupled receptor 68 in animal models to reverse inflammatory and fibrotic pathways, thereby improving kidney function. These same pathways were shown to be dysregulated in human CKD, providing strong evidence that the therapeutic effects observed in pre-clinical models will translate to the clinic. Using a novel mechanism of action, asengeprast has the potential to significantly improve the lives of patients with CKD.
Assessing the Drivers of Wasting among Children Under 5 and Their Mothers in The Bay and Hiran Regions of Somalia
Authors: Grounds Samantha , Walton Shelley , Alier Kemish Kenneth , Garretson Sydney , Mohamoud Said Aden , Abdikadir Sadiq , Khattak Qundeel , Nur Mohamud Ali , Mohamoud Abdullahi Muse , Omer Meftuh , Mahat Mohamed Billow , Mohamed Adam Abdulkadir , Mohamed Abdifatah , Tripaldi Marina , Akseer Nadia
Published: February 2025

Background

To address Somalia’s high burden of wasting, it is imperative to understand the country’s context-specific drivers of wasting. This study assessed the drivers of wasting among children under 5 (CU5) and mothers in Somalia’s Bay and Hiran regions to inform strategies to address wasting.

Methods

The data comes from the midline (September 2023) and endline (December 2023) data collection of a randomized controlled trial. Child and maternal outcomes (weight-for-height z-scores (WHZ) and mid-upper arm circumferences (MUAC), respectively) were explored continuously for children via linear regression and as binary outcomes via Poisson regression for children and mothers. A hierarchical model building approach was used, mapping variables into the basic, intervention, underlying, and immediate levels. Separate midline and endline models were analyzed cross-sectionally, comparing drivers by seasonality, and CU5 models were further stratified by region and age.

Results

The burden of CU5 wasting was 12.9% at midline and 14.4% at endline. The following variables were drivers of low WHZ across different models: child illness, open defecation, low maternal MUAC, no maternal education, having a male-headed household, and living in a household without joint decision-making. Egg/flesh food consumption and higher maternal MUAC were protective of WHZ. Wasting among mothers was 8% at midline and 12% at endline. Household food insecurity, open defecation, and poor waste disposal practices were drivers of mothers’ wasting, whereas maternal decision-making was protective.

Conclusion

This study highlights variation in the key drivers of wasting by region, season, and child age and contributes to an expanding body of evidence on the multifactorial drivers of wasting, encouraging context-specific approaches that address the immediate, underlying, and basic causes of malnutrition. The findings emphasize the importance of maternal nutrition for child nutrition outcomes and the need for interventions considering household food security, sanitation, and gender dynamics in this humanitarian setting.

Registration:The cluster-RCT is registered at ClinicalTrials.gov, ID:NCT06642012.
Risk Behavior, Backward Bifurcation, and Vaccine Effectiveness in Disease Dynamics
Authors: Pedroza-Meza Irasema , Acuña-Zegarra M. Adrian , Velasco-Hernández Jorge X.
Published: February 2025

Many studies have shown that vaccines are not completely effective, meaning that a vaccinated population includes both people who develop immunity from the vaccine and those who, despite being vaccinated, do not. This can be problematic, as some vaccinated individuals may mistakenly believe they are fully protected and cannot acquire the disease. This perception can significantly influence behavior, leading some vaccinated people to be less diligent in following preventive or mitigation measures.

Motivated by the above, we examine how behavioral changes in vaccinated people who do not develop immunity influence the dynamics of a directly transmitted disease and key indices such as the basic reproductive number and vaccine effectiveness. We propose a model that considers a vaccine with three facets of failure: “take”, “degree”, and “duration”. Additionally, the behavioral change of non-immune vaccinated individuals is modeled through a parameter that adjusts their contact rate based on compliance with mitigation measures.

Our results allow us to visualize the role of behavioral change in various factors influencing disease transmission dynamics. First, we demonstrate the existence of a backward bifurcation common in models for not fully effective vaccines. Second, we define a behavioral index threshold, which serves as a key indicator for determining whether the disease persists due to behavioral effects. Finally, our results highlight that both the behavioral index and the initial value of the infected population can play a decisive role in determining whether vaccine effectiveness reaches negative values.