bluuebunny/crossref_metadata_2025 huggingface dataset:
The association between headphones use during study and concentration among medical student at King Khalid University: A cross-sectional study
Authors: Alshaikh Ayoub Ali , AlAmri Ali Mohammed , Albraik Meteb Ahmad , Amer Khaled Abdulwahab N. , Alqahtani Ali Abdullah A. , Almugharrid Rayan Mohammed S. , Alzuhari Abdulmohsin Mohammed S. , Alshahrani Omair Mohammed O. , Mahmood Syed Esam
Published: February 2025

Headphones are commonly used by students to enhance concentration, particularly in high-pressure academic settings. However, the impact of headphone use on concentration and the potential health risks associated with prolonged use remain underexplored. This study examines the relationship between headphone use during study sessions and its effect on concentration among medical students. A cross-sectional survey was conducted among 359 medical students at King Khalid University, Abha, Saudi Arabia. The survey assessed demographic characteristics, headphone usage habits, perceived concentration levels, advantages and disadvantages of headphone use, and anxiety status. Among participants, 40% (n = 143) reported using headphones while studying. Headphone use was more prevalent among females (59.2%), sixth-year students (33.1%), and those from higher-income families (43.7%). Logistic regression analysis revealed significant associations between demographic factors and headphone use. Students using headphones for longer durations reported higher concentration levels and improved learning outcomes. Key advantages included blocking external distractions (53.5%), improving focus (47.9%), and enhancing study enjoyment (39.6%), while disadvantages included reduced situational awareness (52.8%). Higher volume levels correlated with increased concentration, with 50% of high-volume users reporting very high concentration. Additionally, family income level was significantly associated with concentration, with students from higher-income families exhibiting greater focus. Headphone use during study sessions is associated with increased concentration among medical students. Understanding usage patterns and their effects on academic performance is crucial for optimizing study environments and promoting effective learning strategies in medical education.
“After the horrible cancer…” Post-traumatic growth through the lens of head and neck cancer survivors
Authors: Menger Fiona , Deane Jennifer , Patterson Joanne M. , Fisher Peter , O'Hara James , Sharp Linda
Published: February 2025

Background:

This qualitative study aimed to enhance understanding of the psychosocial processes underlying post-traumatic growth (PTG) following head and neck cancer (HNC) by exploring survivors' experiences following completion of treatment.

Methods:

We interviewed twenty HNC survivors (9 months to 5 years after diagnosis) about their cancer diagnosis and treatment, including any perceived positive changes. Based on an existing model on PTG, we used a directed content analysis to identify descriptions of PTG. We adopted open coding to explore these experiences and to construct new themes. We then re-examined interviews of those who expressed few or no positive changes.

Results:

Analysis led to the creation of 5 themes: gratitude and compassion, re-evaluation, clarity and purpose, mindfulness and awareness, and complexities and adjustment challenges. The first 4 themes revolved around how HNC had led to changes in participants' sense of self, their value and perception of others, and their life roles and priorities. The final theme, constructed from interviews with little or no PTG, reflected ongoing or co-occurring trauma and lack of control or resolution.

Conclusions:

PTG following HNC represented a range of positive experiences. Social support and the ability to engage in proactive and reflective behaviors to support their recovery appeared to play a role in these outcomes. Not all HNC survivors report positive changes; it may be worthwhile focusing future research on identifying and supporting those who struggle to move on from their experiences.
Oxygen Saturation Sub-analyses Errors in the Dominant Meta-analysis Used to Deimplement Albuterol as a Therapeutic Option for Bronchiolitis
Authors: Mellick Larry , Weston Gabriella , Walsh Paul , McKinney Shane , Xu Hongyan
Published: February 2025

Objective:

Clinical experience and patient-level physiological studies indicate that albuterol transiently reduces oxygen saturation, irrespective of the underlying respiratory condition causing the wheezing. Three revisions of the Cochrane review, Bronchodilators for Bronchiolitis (Review), have found that albuterol temporarily increases oxygen saturation. Rarely, these findings were even statistically significant, but the direction of effect is consistently opposite from physiological studies. In this study, we attempted to resolve this apparent paradox.

Methods:

The original trial publications included in multiple oxygen saturation sub-analyses in the 2006, 2010, and 2014 updates of the Cochrane review were assessed for appropriate study inclusion, correctness of calculations, and correct analysis with respect to direction of effect. The studies were also reviewed to assess whether the data was correctly transferred to the meta-analysis software. We repeated the meta-analyses calculations after correcting for suspected errors and plotted the results of the meta-analyses as originally reported and in their corrected form on an albatross plot.

Results:

We found data miscalculations, errors of transposition of albuterol and placebo data, the inclusion of inpatient data in outpatient analyses, and questionable study inclusions in the 3 Cochrane review updates. After corrections were made, the direction of effect of albuterol switched negative, albeit nonsignificantly, a finding most consistent with clinical and physiological observations. In addition, the very wide heterogeneity between the original meta-analyses disappeared.

Conclusion:

After multiple suspected data flaws were corrected our reanalyses of the reported data confirmed that decreased oxygen saturation can be expected following administration of albuterol to infants presenting with bronchiolitis syndrome, thereby resolving the apparent paradox in favor of clinical observation and research physiology.
Efficacy of mobile health interventions in the conservative management of chronic low back pain in low- and middle-income countries: a systematic review, meta-analysis, and trial sequential analysis
Authors: Rani Babina , Gupta Mayank , Ganesh Venkata , Sharma Rajni , Bhatia Anuj , Ghai Babita
Published: February 2025

Chronic low back pain (CLBP) is a major global health issue, particularly severe in low- and middle-income countries (LMICs), where health care resources and accessibility are limited. Mobile health (mHealth) interventions offer a promising solution by leveraging technology to deliver health care services remotely. This review aims to evaluate the effectiveness of mHealth interventions in managing CLBP in LMICs. A comprehensive search of electronic databases was performed for studies published until June 2024, evaluating mHealth interventions for CLBP in LMICs. Primary outcomes measured were pain intensity and disability, while secondary outcomes included quality of life (QoL). Risk of bias was assessed using Cochrane risk-of-bias tool (RoB2), and quality of evidence was evaluated using GRADE. Robustness of meta-analysis results was assessed via trial sequential analysis (TSA). Seven studies met the inclusion criteria. The mHealth interventions significantly reduced the overall pain intensity (MD = −1.11, 95% CI: −1.75, −0.46) and disability (MD = −6.59, 95% CI: −10.65, −2.54). Subgroup analysis indicated greater effectiveness of short-term interventions (<6 weeks) in reducing pain and Oswestry disability index (ODI) vs long-term interventions (>6 weeks). mHealth interventions notably reduced pain and ODI scores vs unsupervised programs but showed no significant difference compared to in-person programs. The z-score line remained within TSA boundaries. mHealth interventions show potential in reducing pain and disability among patients with CLBP in LMICs, although with inconclusive impact on QoL. The high heterogeneity and limited number of studies underscore the need for further research with greater sample size to validate these findings and explore the long-term benefits and implementation challenges of mHealth in resource-constrained settings.
Radiation Exposure to Patients and Others During Therapy for Pediatric Neuroblastoma With Lu-177-DOTATATE
Authors: Lu Zhaoqi , Sun Yanjinghui , Zuo Di , Li Pengfei , Sun Xiaorong
Published: February 2025

Purpose:

This study evaluated Lutetium-177-(DOTA°,Tyr3) octreotate (Lu-177-DOTATATE) clearance in pediatric patients with neuroblastoma and assessed the effective doses received by patients, family caregivers, and medical staff during therapy.

Patients and Methods:

Twenty-three children (3–13 y) who received Lu-177-DOTATATE between 2023 and 2024 were enrolled. External dose rates were measured at 0, 1, 2, 4, 6, 24, 48, and 96 hours post-administration to estimate patients’ Lu-177-DOTATATE retention rate, the effective half-life, and the maximum cumulative effective dose around patients. Whole-body and red-marrow absorbed doses were calculated based on multi-time-point whole-body planar and SPECT/CT imaging using HERMES Dosimetry software. Whole-body effective doses to family caregivers and medical personnel were measured using thermoluminescence dosimeters (TLDs), and effective finger doses for medical staff were measured using ring TLDs.

Results:

The mean administered activity was 3.687±1.545 (range, 1.469–7.368) GBq. Whole-body retention rates at 1–96 hours post-administration ranged from 72.0% to 10.0%, with 99% clearance expected within 11 days. Clearance followed a biexponential decay model, with estimated effective half-lives of 1.4±0.8 and 52.3±18.6 hours for the fast and slow phases, respectively, at 2 m. Estimated maximum cumulative effective doses (within 11 days) at 1 and 2 m were 0.442±0.174 and 0.138±0.058 mSv, respectively. Absorbed doses for children were 0.159±0.076 mGy/MBq (whole body) and 0.611±0.416 mGy/MBq (red-marrow). Whole-body effective doses to family caregivers averaged 0.245±0.063 (range, 0.150–0.390) mSv. The whole-body and finger-effective doses to the radiopharmacists were 3.7±1.8 and 155.3±73.0 μSv/patient, respectively. The mean of whole-body and the median (P
25, P
75) of finger-effective doses to nurses were 4.7±1.4 μSv/patient and 16.7 (10, 470) μSv/patient, respectively.

Conclusion:

Lu-177-DOTATATE was rapidly cleared in children with neuroblastoma. Radiation exposure to others was below personal dose limits.
18F-FDG PET/CT in Seronegative Paraneoplastic Limbic Encephalitis Related to Gastrointestinal Stromal Tumor With Coexisting Sepsis
Authors: Kumar Srinivas Ananth , Srivastava Madhur Kumar , Uppin Megha Shantiveer , Malladi Venkata Surya Subbalaxmi
Published: February 2025

Paraneoplastic limbic encephalitis (PLE) is proposed to be triggered by oncoantibodies in response to the malignancies, which cross-react with the self-antigens in the neurons. Patients usually manifest a wide range of clinical presentations and neuropsychiatric symptoms like memory loss, mood changes, behavioral disorders, altered state of consciousness, and seizures. Lung carcinoma is the most common malignancy associated with PLE. Antibodies to common intracellular antigens have been associated with PLE, however, not all patients demonstrate the association. Here the authors demonstrate a rare association of seronegative PLE in a patient with gastrointestinal stromal tumour.
Danger in the “Shadows”: Rib Cartilage Histomechanics
Authors: Yegin Mehmet E. , Pekedis Mahmut , Ates Gizem , Eroglu Ebru , Uyanigil Yigit , Ceylan Naim , Bilge Okan
Published: February 2025

Warping has always been accused of the unsatisfying results of rib cartilage. However, as noticed before, microanatomic transitions of the cartilage tissue may have caused altering of the biomechanical properties of the rib cartilage. With this hypothesis, the authors aimed to scrutinize the signs of histologic and biomechanical details of rib cartilage. In 2 cadavers, the fifth to eighth cartilages were harvested after CT scans. As the authors found a “shadowy” view on CT scans in our previous study, these areas were tested with biomechanical tests and histology in the current study. The results showed significantly differing microstructures in these areas, including immature cartilage structures.
Knowledge of Pelvic Floor Disorders in English- and Spanish-Speaking Postpartum Patients
Authors: Siddique Moiuri , Passarelli Emily , Shi Carol , Myers Deborah
Published: February 2025

Importance

Postpartum patients generally have limited knowledge of urinary incontinence (UI) and pelvic organ prolapse (POP). However, it is unclear what differences exist in knowledge level between English- and Spanish-speaking postpartum patients for each condition.

Objective

The objective of this study was to report rates of knowledge proficiency on UI and POP in English- and Spanish-speaking postpartum patients.

Study Design

In this cross-sectional study of postpartum patients at a tertiary care center, knowledge was assessed using the English and Spanish language–validated Prolapse and Incontinence Knowledge Questionnaire. Knowledge proficiency on UI was defined as answering correctly ≥80% of the questions and for POP as answering correctly ≥50% of the questions, based on cutoffs implemented by Geynisman-Tan et al previously. Pelvic floor disorder symptom severity was assessed using the Pelvic Floor Distress Inventory-20 and the Pelvic Floor Impact Questionnaire-7.

Results

Fifty English- and 50 Spanish-speaking patients completed the survey questionnaires. Spanish-speaking patients had lower rates of UI proficiency compared to English-speaking patients (10.0% vs 40.0%, P < 0.001) and were less likely to identify childbirth to be a risk factor for UI compared to English-speaking patients. For POP, proficiency levels were low but similar between English and Spanish speakers. Pelvic floor disorder symptom severity and impact on quality of life were low, did not differ between the 2 groups, and did not correlate with knowledge scores.

Conclusion

English- and Spanish-speaking postpartum patients have low knowledge of both UI and POP. Postpartum patients need educational resources to understand the risks and treatments for pelvic floor disorders.
Diabetes With Elevated A1C is Related to Perceptual Speed Decline in Older Adults
Authors: Biswas Roshni , Capuano Ana W. , Moran Chris , Bennett David A. , Arvanitakis Zoe
Published: February 2025

Our objective was to examine the association of persistently elevated A1C with global and domain-specific cognitive function, in a large group of older adults with and without diabetes. Our study included 3038 participants from 5 ongoing community-based longitudinal studies of aging and dementia at the Rush Alzheimer's Disease Center. Annual evaluation included medical history, medications, collection of blood specimens, and neuropsychological testing. We created 2 time-varying variables: one for the period of persistently elevated A1C starting at the first of 2 consecutive A1C levels ≥6.5%, and another for participants’ diabetes status. Using separate mixed effect models, persistently elevated A1C was associated with higher levels of global cognition (estimate = 0.045; P = 0.03) and specifically with episodic memory (estimate = 0.082; P < 0.01). Further, persistently elevated A1C was related to a faster decline in perceptual speed (estimate = −0.014; P < 0.01). Persons with diabetes who had elevated A1C drove this finding (estimate = −0.02; P < 0.01). Our findings suggest a differential effect of sustained hyperglycemia by cognitive domain.
Maternal and Fetal Complications Among Pregnant Women with Congenital Heart Disease
Authors: Patel Shayli , Raskind-Hood Cheryl , Wilson Travis , Rodriguez Fred H. , Haffner Alex , Kancherla Vijaya , Ivey Lindsey , Book Wendy M.
Published: February 2025

Background

Survival to reproductive age is now common among women with congenital heart disease (CHD). Pregnancies to women with CHD may be at higher risk for maternal and fetal complications. This study examines maternal and fetal outcomes among pregnant women with CHD covered by Georgia Medicaid.

Methods

This case-control study identified 3,461 pregnant women with CHD, 11-50 years, covered by Georgia Medicaid from 2008-2019, who had 5,904 pregnancies. Maternal and fetal outcomes were determined by ICD-9-CM and ICD-10-CM codes at the encounter level. The association of select covariables, including race/ethnicity, social deprivation, CHD native anatomy, rurality, and presence of pre-existing maternal comorbidities on maternal and fetal outcomes were analyzed using chi-square. Multivariate logistic regression models adjusting for covariates were conducted.

Results

Women with severe CHD had more fetal complications and fetal deaths/stillbirths than women with non-severe CHD (53.9% vs. 50.2% p=0.01 and 4.4% vs. 3.0%, p=0.007, respectively), but no difference in maternal complications were revealed (60.7% vs. 59.9%, p=ns). In multivariate analysis, pregnancies to women with severe CHD were 25% more likely to have fetal complications than pregnancies to women with non-severe CHD (aOR 1.25, 95CI 1.07-1.47). The most common fetal complications by maternal CHD anatomy were fetal distress, fetal growth restriction, and preterm delivery (27.2% vs. 23.1%, 27.6% vs. 19.4%, 23.1% vs. 19.6% for severe vs. non-severe, respectively, p=<0.05).

Conclusions

Pregnancies to women with CHD were associated with a high rate of maternal and fetal complications. Fetal complications, fetal death and stillbirth were highest among women with severe CHD.
Beyond the Checklist: A large-scale analysis of under-recognised weight loss behaviours in individuals with eating disorders
Authors: Kakar Saakshi , Foye Una , Davies Helena L. , Palaiologou Elisavet , Malouf Chelsea M. , Meldrum Laura , Smith Iona , Kalsi Gursharan , Allen Karina L. , Breen Gerome , Herle Moritz , Hübel Christopher
Published: February 2025

Objective

This study aimed to identify and categorise under-recognised weight loss behaviours in individuals with eating disorders, addressing diagnostic gaps.

Method

We text mined free-text responses from 1,675 participants with anorexia nervosa, bulimia nervosa, or binge-eating disorder in the Genetic Links to Anxiety and Depression (GLAD) Study and the United Kingdom Eating Disorders Genetics Initiative (EDGI UK). In secondary analyses, we investigated differences by eating disorder and gender.

Results

Frequently endorsed behaviours included structured diets (341 endorsements) and calorie counting (321 endorsements) but also less commonly considered behaviours like compression garments (113 endorsements) and self-harm (63 endorsements). We identified four overarching themes: restriction-based approaches, medical intervention, body manipulation, and food avoidance. The most frequently reported weight loss behaviours and resultant themes did not differ among eating disorders or genders, closely resembling those in the broader sample.

Discussion

Our findings identify a crucial gap in current diagnostic criteria, which may hamper recognition and lead to underdiagnosis of eating disorders. By incorporating our insights, clinicians could capture a broader spectrum of behaviours, thus improving diagnostic accuracy. However, our sample homogeneity implicates the need for more diverse samples. Our study contributes essential insights for enhancing diagnostic criteria.

Public Significance Statement

Our study revealed under-recognised weight loss behaviours in people with eating disorders that current diagnostic tools miss, which may lead to underdiagnoses. By identifying these behaviours and taking a broader diagnostic approach, our research can help clinicians better understand eating disorders by improving diagnostic accuracy and opening up new avenues for personalised care.
Age-related differences in Rostral-Middle Locus Coeruleus Microstructure: A Critical Role in Cognitive Decline Revealed by Magnetic Resonance Relaxometry
Authors: Bae Jonghyun , Gong Zhaoyuan , Mazucanti Caio , Bilgel Murat , Laporte John P. , Faulkner Mary E. , Guo Alex , Bergeron Christopher M. , Egan Josephine M. , Resnick Susan M. , Ramsden Christopher E. , Bouhrara Mustapha
Published: February 2025

BACKGROUND

The Locus Coeruleus (LC) is a critical brain region affected by neurodegenerative diseases and cognitive decline in aging. Despite its importance, in-vivo investigations of age-related LC degeneration and association with cognitive decline have been limited.

METHOD

We employed the Bayesian Monte-Carlo analysis of multicomponent driven equilibrium single pulse observation of T1and T2(BMC-mcDESPOT) method to estimate longitudinal (R1) and transverse (R2) relaxation rates in the LC of a diverse cohort of cognitively unimpaired individuals aged 22 to 94 years. BMC-mcDESPOT offers high spatial resolution and is effective for mapping detailed microstructural changes within the LC as reflected by R1and R2. We examined age-related differences in LC microstructure, their associations with cognitive changes, and the spatial variation of these microstructural changes within the LC, exploring their distinctive contributions to cognitive decline.

RESULTS

Age was significantly associated with LC microstructural integrity, with advanced ages exhibiting lower R2values. We also found that lower LC- R1and LC-R2are correlated with steeper decline longitudinally in multiple cognitive domains, including memory, verbal fluency, processing speed and executive function. Furthermore, we observed distinctive spatial variations between young and old participants, with R1and R2values in the rostral-middle regions being more strongly associated with cognitive changes as compared to the caudal region.

CONCLUSIONS

This study reveals age-related differences in LC integrity, which are associated with cognitive decline. LC relaxometry metrics (R1and R2values) may serve as sensitive biomarkers for detecting early alterations and age-related cerebral degeneration.
Trajectories of microbiome-derived bile acids in early life – insights into the progression to islet autoimmunity
Authors: Lamichhane Santosh , Dickens Alex M , Buchacher Tanja , Lou Evita Tianai , Charron-Lamoureux Vincent , Kattelus Roosa , Karmacharya Pragya , Pinto da Silva Lucas , Kråkström Matilda , Rasool Omid , Sen Partho , Walker Corinn , Patan Abubaker , Gentry Emily C. , Arzoomand Aron , Lakshmikanth Tadepally , Mikeš Jaromir , Mebrahtu Aman , Vatanen Tommi , Raffatellu Manuela , Zengler Karsten , Hyötyläinen Tuulia , Xavier Ramnik J. , Brodin Petter , Lahesmaa Riitta , Dorrestein Pieter C. , Knip Mikael , Orešič Matej
Published: February 2025

Recent studies reveal that gut microbes produce diverse bile acid conjugates, termed microbially conjugated bile acids (MCBAs). However, their regulation and health effects remain unclear. Here, we analyzed early-life MCBA patterns and their link to islet autoimmunity. We quantified 110 MCBAs in 303 stool samples collected longitudinally (3– 36 months) from children who developed one or more islet autoantibodies and controls who remained autoantibody-negative. Stool MCBAs showed distinct age-dependent trajectories and correlated with gut microbiome composition. Altered levels of ursodeoxycholic and deoxycholic acid conjugates were linked to islet autoimmunity as well as modulated monocyte activation in response to immunostimulatory lipopolysaccharide and Th17/Treg cell balance. These findings suggest MCBAs influence immune development and type 1 diabetes risk.
Biomechanical assessment of upright birthing positions using marker-based and markerless motion capture systems
Authors: Haworth Lauren , Kaur Inderjeet , Ahmed Maimoona , Topalidou Anastasia
Published: February 2025

Understanding the effects of birthing positions on labour is crucial for optimising maternal and foetal outcomes. Upright positions are encouraged but their biomechanics are not fully understood. Biomechanical changes during labour can make certain positions more or less favourable depending on individual physical characteristics. Understanding these factors is essential for tailoring strategies that enhance maternal comfort and facilitate labour. This study aimed to quantify the biomechanics of seven common upright birthing positions, comparing their biomechanical characteristics and evaluating the sensitivity and accuracy of marker-based and markerless motion capture systems. Fifteen healthy, non-pregnant women performed seven upright birthing positions. Hip, pelvis, and trunk kinematics were assessed using a 9-camera marker-based system and an 8-camera markerless system. Significant biomechanical differences were found between birthing positions. The “squat” position showed the most hip flexion and abduction, “B-Ball” had the greatest anterior pelvic tilt, and “all-fours” exhibited the most posterior tilt. For the trunk, “upright” led to the most extension, and “elbows bent knees” showed the most flexion. The markerless system aligned well with the marker-based system in the coronal and transverse planes but lacked sensitivity in the sagittal plane. This study highlights the biomechanical differences in upright birthing positions and emphasises the need for personalised birthing strategies. Understanding labour biomechanics is crucial for improving maternal and foetal well-being and reducing complications. By providing comprehensive and evidence-based information, women can make informed decisions about their birthing positions, enhancing outcomes and lowering the risk of maternal and neonatal complications globally.
Complex Traces: Using a Complex Adaptive Systems approach to examine morbidity and mortality among 19th Century migrants to South Australia
Authors: Gurr Angela , Brook O’Donnell Matthew , Brook Alan Henry
Published: February 2025

In multidisciplinary research interpreting interactions between diverse data sources requires a Complexity approach. A Complex Adaptive Systems (CAS) framework allows the relationships of multiple factors to be explored and may provide a more holistic and nuanced understanding. This study is innovative in explaining the potential benefits in a CAS approach to combining bioarchaeological and historical data when examining a rare archaeological skeletal sample of early migrants to South Australia (SA).

Macroscopic, radiographic and micro-CT methods were used for the analysis of the skeletal remains of a group of 19thcentury migrants buried in an unmarked area of St Mary’s Anglican Church Cemetery. The relevant historical records explored were from British emigrant ships to SA (1836 to 1885) and the Church burial records (1847-1885).

Evidence of poor oral and general health was present in the skeletal material. Dental developmental defects indicated earlier health insults. Pathological manifestations in bone were compatible with joint and infectious diseases, and metabolic deficiencies. Historical documents recorded that the voyages to SA were challenging, with some ships experiencing a high death rate. Diseases e.g., measles and scarlet fever, and diarrhoea were frequently recorded as causes of death at sea for both subadults and adults. In the Colony, burial records showed similar causes of death for subadults, but for adults, accidents and tuberculosis were often reported.

The CAS approach provided insights beyond those from analysis of the individual sources. It increased understanding of emergent, non-predicted outcomes that resulted from interactions between multiple factors e.g., the impact of fluctuating economy, political instability and ideological pressures, on the health of migrants. The CAS framework is a valuable methodology for interpreting health patterns and can be further developed for a range of historical and contemporary health contexts.
AMPK mediates the anti-ferroptosis effect of acupuncture in cerebral ischemia-reperfusion rats
Authors: Wang Rong , Xu Jun-feng
Published: February 2025

Background

Acupuncture is clinically effective in the treatment of ischemic stroke. The report suggests that energy stress inhibits ferroptosis in part through AMPK. However, whether the effect of activating AMPK is related to ferroptosis in ischemic stroke and whether acupuncture can achieve neuroprotection against ischemic brain injury through the pathway of inhibiting ferroptosis by activating AMPK has not been confirmed.

Methods

In this experiment, all rats were randomly divided into 4 groups: Sham group, MCAO/R group, MA (MCAO/R + acupuncture) group, and MAM (MCAO/R + acupuncture + metformin) group. The middle cerebral artery occlusion/reperfusion injury (MCAO/R) model was created by the wire embolism method, and the MA and MAM groups received acupuncture treatment with electrotherapy (1 mA, 2/15 Hz, 20 min each), while the MAM group continued to receive metformin (oral gavage 200 mg/kg) after successful modelling. Neurological deficit score and infarct volume were measured, Prussian blue staining and mitochondrial structural changes were observed, and Fe2+ and MDA levels were determined in the brain tissue of the rats. Western blot results were analyzed to determine differences in the expression of TFR1, SLC7A11, GPX4 and AMPK、 p-AMPK proteins in order to explore the possible pathological processes involved in cerebral ischemia at behavioral, histological and molecular levels and the possible protective mechanisms of acupuncture.

Results

Acupuncture attenuated ischemia-reperfusion-induced brain damage and mitochondrial damage. Further studies showed that acupuncture reduced the levels of Fe2+, MDA and the expression of TFR1 protein and increased the expression of SLC7A11 and GPX4 protein in the diseased hippocampal region of MCAO/R rats. In addition, metformin, as an AMPK activator, significantly enhanced the protective effect of acupuncture on cerebral ischemic injury and enhanced the acupuncture-mediated reduction of Fe2+, MDA levels and TFR1 protein expression and the increase of SLC7A11 and GPX4 protein expression in the lesioned hippocampal region of MCAO/R rats.

Conclusions

These findings suggest that acupuncture can inhibit ferroptosis and thus exert a protective effect against ischemic brain injury, and that this mechanism may be achieved by activating AMPK. This extends the mechanism of action of acupuncture in the treatment of ischemic stroke.
Deep learning predicts tissue outcomes in retinal organoids
Authors: Afting Cassian , Bhatti Norin , Schlagheck Christina , Salvador Encarnación Sánchez , Herrera-Astorga Laura , Agarwal Rashi , Suzuki Risa , Hackert Nicolaj , Lorenz Hanns-Martin , Zilova Lucie , Wittbrodt Joachim , Exner Tarik
Published: February 2025

Retinal organoids have become important models for studying development and disease, yet stochastic heterogeneity in the formation of cell types, tissues, and phenotypes remains a major challenge. This limits our ability to precisely experimentally address the early developmental trajectories towards these outcomes. Here, we utilize deep learning to predict the differentiation path and resulting tissues in retinal organoids well before they become visually discernible. Our approach effectively bypasses the challenge of organoid-related heterogeneity in tissue formation. For this, we acquired a high-resolution time-lapse imaging dataset comprising about 1,000 organoids and over 100,000 images enabling precise temporal tracking of organoid development. By combining expert annotations with advanced image analysis of organoid morphology, we characterized the heterogeneity of the retinal pigmented epithelium (RPE) and lens tissues, as well as global organoid morphologies over time. Using this training set, our deep learning approach accurately predicts the emergence and size of RPE and lens tissue formation on an organoid-by-organoid basis at early developmental stages, refining our understanding of when early lineage decisions are made. This approach advances knowledge of tissue and phenotype decision-making in organoid development and can inform the design of similar predictive platforms for other organoid systems, paving the way for more standardized and reproducible organoid research. Finally, it provides a direct focus on early developmental time points for in-depth molecular analyses, alleviated from confounding effects of heterogeneity.
Inhibition of methylthioadenosine phosphorylase provides protection from experimental acute kidney injury
Authors: Saliba Afaf , Chen Yidong , Nelson Jonathan W. , Vetcha Abhinav , Wang Wei Wei , Kang Li , Ragi Nagarjunachary , Maity Soumya , Rabb Hamid , Reeves W. Brian , Sharma Kumar
Published: February 2025

Acute kidney injury (AKI) increases mortality risk and predisposes individuals to chronic kidney disease. Metabolic pathways play a crucial role in AKI pathophysiology. Here, we investigate the potential of methylthioadenosine phosphorylase (MTAP) inhibition as a novel renoprotective strategy in AKI. Using AKI mouse models, we demonstrate that a small molecule MTAP inhibitor significantly reduces kidney injury markers and improves renal histology. RNA sequencing reveals that MTAP inhibition modulates pathways associated with inflammation, oxidative phosphorylation, and cell survival. Additionally, analysis of human single-cell RNA sequencing data links MTAP expression to kidney injury marker in AKI. This study provides evidence of MTAP inhibition as a potential therapeutic strategy for AKI, highlighting metabolic dysregulation as a target for future clinical interventions.
NEDD4 promotes Sertoli cell proliferation and adult Leydig cell differentiation in the murine testis
Authors: Windley Simon P. , Neirijnck Yasmine , Vidovic Diana , Schwarz Quenten , Kumar Sharad , Nef Serge , Wilhelm Dagmar
Published: February 2025

Successful testis development relies on the coordinated differentiation and assembly of various cell types to establish both endocrine and reproductive functions. The ubiquitin ligase NEDD4 has emerged as a key player in murine testis development, with this enzyme being implicated in gonadal sex determination and spermatogonial stem cell differentiation. Here, we report hitherto uncharacterized roles of NEDD4 in postnatal testis development. UtilizingNr5a1-andAmh-Cre drivers to conditionally ablateNedd4in testicular somatic cells, we show that NEDD4 promotes Sertoli cell proliferation through the modulation of the PI3K-AKT signaling pathway. This ubiquitin ligase also ensures proper differentiation of adult Leydig cells and may contribute to murine steroidogenesis. Furthermore, NEDD4 is essential for adrenal gland differentiation, as its loss results in adrenal dysgenesis. These findings highlight NEDD4 as a crucial factor in testis development, emphasizing the importance of ubiquitination and post-translational modifications in reproductive biology.
Inferring Latent Behavioral Strategy from the Representational Geometry of Prefrontal Cortex Activity
Authors: Qian Yichen , Herikstad Roger , Libedinsky Camilo
Published: February 2025

Behavioral tasks can be solved employing various strategies. Sometimes, different strategies result in the same observable behavior, making them latent. In this study, we infer the latent behavioral strategy used by monkeys in a working memory updating task by comparing the representational geometry of two prefrontal regions —the lateral prefrontal cortex (LPFC) and the prearcuate cortex (PAC)—with that of recurrent neural network (RNN) models trained to solve the task using different strategies. We found that neural activity patterns in both LPFC and PAC align with only one of the proposed strategies, suggesting that monkeys employ this latent strategy to perform the task. These findings open avenues for investigating the processes that lead to strategy learning and the decision-making mechanisms that determine which strategies are chosen when multiple options are available.
Dynamic Monomer-Dimer Transition in Ligand-induced Apelin Receptor Activation
Authors: Ji Su-Yu , Wang Wei-Wei , Yang Yixin , Xu Ping , Zhang Jiangrong , Zhao Xinyue , Xi Kun , Zang Shao-Kun , Shen Dan-Dan , Mao Chunyou , Shen Qingya , Zhang Yan
Published: February 2025

G-protein-coupled receptors (GPCRs) are significant signal transducers that exist as monomers and in multiple oligomeric forms. However, molecular mechanism driving their dynamic interconversion to regulate intricate signaling in class A GPCRs remains elusive, compounding our understanding of their related pathophysiological functions. Here, we present a set of 12 assemblies of the apelin receptor (APLNR), including dimeric apo state, monomeric and dimeric intermediate states and fully active state stimulated by small molecule or nanobody, providing a detailed dynamic view of the monomer-dimer transition. High-resolution cryo-EM structures reveal that different ligands induce varying degrees of pre-dissociation in intermediate-state dimers, with G-protein coupling facilitating the transition from dimeric to monomeric receptor. Functional studies further highlight the critical role of cholesterol clusters in stabilizing the APLNR dimers. These insights enhance our understanding of the dynamic regulation of class A GPCRs across different aggregated forms and advance the rational drug design strategies aimed at selectively modulating of APLNR signaling.
Changes in oral risk habits and influencing factors among participants in an oral cancer screening program
Authors: Munpolsri Pattaranan , Su Chiu-Wen , Yang Hsu-Fei , Hsu Tsui-Hsia , Chou Yen-Yu , Lin Li-Ju , Wu Chao-Chun , Chen Sam Li-Sheng , Yen Amy Ming-Fang
Published: February 2025

This study examines changes in oral risk habits and identifies factors influencing these changes among participants in a population-based oral cancer screening program to support effective public health interventions. The study included 2,569,920 individuals aged 30 and older who participated in Taiwan’s Oral Cancer Screening Program at least twice between 2010 and 2021. Changes in cigarette smoking and betel quid chewing were assessed between the first and last screenings and categorized as improved, unchanged, or worsened. A logistic regression model evaluated factors associated with habit improvement, including baseline oral habits, sex, age, education, screening adherence, and oral potentially malignant disorder (OPMD) findings.

Among participants, 25.3% improved their oral habits. Baseline habits influenced how OPMD screening results affected behavior change. Among smokers, a positive screening result increased the likelihood of quitting or reducing smoking (adjusted odds ratio [aOR] = 1.18, 95% CI 1.16–1.20). However, among betel quid chewers, whether or not they smoked, a positive screening result was negatively associated with improved habits (aOR 0.79–0.88). Being female, older, college-educated, and regularly attending screenings were positively linked to behavior improvement.

The program led to habit improvements in about one-quarter of participants, particularly older individuals, those with higher education, and frequent attendees. However, a diagnosis of OPMD motivated change only among smokers, not those engaging in both smoking and betel quid chewing, highlighting a lack of awareness in high-risk groups. Strengthening collaboration between health organizations and the screening program could enhance public awareness, improve program effectiveness, reduce oral cancer incidence, and lower long-term healthcare costs.
Comparative assessment of combined concentration and extraction methods for Influenza A and B virus detection in wastewater
Authors: Fretschner Till , Zeisler Edgar Elon , Scheller Steffi , Aurenz Andreas , Schneider Beate , Lukas Marcus , Braun Ulrike , Greiner Timo , Schumacher Jakob , Selinka Hans-Christoph , Walther Birgit , Kallies René
Published: February 2025

Influenza, caused by Influenza A and B viruses, represents a significant global health burden due to recurrent seasonal epidemics and the risk of pandemics. To gauge the large volume of seasonal influenza cases, it may be helpful to complement classical surveillance systems with additional approaches such as wastewater-based epidemiology (WBE), which can aid in the early trend assessment of seasonal epidemics. WBE has emerged as a promising tool for population-level surveillance, enabling the detection of viral nucleic acids in wastewater and offering unique advantages over individual-based surveillance. This study evaluates the performance of six different combinations of virus concentration and RNA extraction methods for the detection of Influenza A and B viruses in wastewater. Composite samples from four wastewater treatment plants in North Germany were analyzed using precipitation, filtration and automated extraction protocols. Method performance was evaluated by quantitative recovery of viral RNA and a spike-and-recovery experiment. The combination of PureYield™ filtration and Maxwell® RSC extraction (PYC_EX1) consistently demonstrated the highest recovery rates for both Influenza virus A and B, achieving recovery efficiencies of up to 80.4% and 72.3%, respectively. This method also enabled reliable detection of low viral loads, which is critical for an early detection of rising incidence. Our findings underscore the importance of rigorous method evaluation to optimize WBE for influenza surveillance. By providing robust, sensitive and reproducible protocols, this study highlights the potential of WBE to improve public health preparedness, enables timely interventions and reduces the spread of influenza viruses within communities.
Somato-cognitive action network in laryngeal and focal hand dystonia sensorimotor dysfunction
Authors: Wang Yuchao , Huynh Baothy , Ren Jianxun , Chen Mo , Zhang Wei , Hu Dan , Li Shasha , Liu Hesheng , Kimberley Teresa J.
Published: February 2025

The central pathology causing idiopathic focal dystonia remains unclear, limiting effective treatment targets. The recently identified somato-cognitive action network (SCAN) with its role in coordinating physiologic processes and coarse movements has been implicated in dystonia dysfunction. SCAN is thought to interface between the phylogenetically newer primary motor regions that control fine movements and the cingulo-opercular network (CON) that putatively conveys cognitive intentions for action. We hypothesized that the effector-agnostic nature of SCAN may constitute a central pathology shared across focal dystonia subtypes affecting different body parts. Additionally, the effector-specific areas in the primary sensorimotor cortex may show distinct functional changes depending on the dystonic body region.

We collected functional MRI from people with either of two subtypes of idiopathic focal dystonia (laryngeal dystonia or LD,N=24, and focal hand dystonia or FHD,N=18) and healthy control participants (N=21). Regions of interest were selected based on prior work that suggested dystonia-related abnormality within the basal-ganglia-thalamo-cortical and cerebello-thalamo-cortical sensorimotor pathways. We investigated if focal dystonia is associated with resting-state functional connectivity changes 1) between SCAN and other cortical regions (effector-specific areas and CON), 2) between cortical and non-cortical regions, or 3) between non-cortical (subcortical and cerebellar) regions. Cortical regions of interest were individualized based on resting-state data. Separately, individualized hand and mouth/larynx regions were also generated from task-based MRI (finger-tapping and phonation, respectively) for comparison.

Results showed a significant interaction effect in both focal dystonia subtypes (p=0.048 for LD,p=0.017 for FHD) compared to controls, which was driven by SCAN’s higher functional connectivity to task-derived mouth/larynx region and concomitantly lower connectivity to CON. This dystonia-dependent interaction was not observed with the resting-state mouth/larynx region. No significant resting-state functional changes were observed involving subcortical and cerebellar regions when LD and FHD were modeled as independent groups. However, exploratory analysis combining LD and FHD as a single group suggested a dystonia-dependent asynchronization between SCAN and sensorimotor cerebellum (p=0.051) that may suggest a pathological rather than compensatory process.

For the first time, our study systematically tested key functional connectivity changes in two focal dystonias. Our results show that SCAN is uniquely associated with dystonia dysfunction beyond the dystonic effector regions, potentially offering insights on pathophysiology and future treatments.
Surgery-induced reduction in inflammation relates to improved neural inhibitory control in obesity
Authors: Kaufmann Lisa-Katrin , Custers Emma , Vreeken Debby , Snabel Jessica , Morrison Martine C. , Kleemann Robert , Wiesmann Maximilian , Hazebroek Eric J. , Aarts Esther , Kiliaan Amanda J.
Published: February 2025

Obesity is associated with impaired inhibitory control and low-grade systemic inflammation. Systemic inflammation adversely affects neurocognitive performance. Here, we investigate the effects of metabolic bariatric surgery on systemic inflammation and its influence on neural mechanisms underlying inhibitory control. In a sample of 47 individuals with obesity, we assessed inhibitory control processing pre- and 2 years post-bariatric surgery by probing neural activation and connectivity during an fMRI Stroop task. We investigated whether surgery-induced changes in plasma markers of systemic inflammation were related to changes in altered neural responses. Data were collected as part of the BARICO (Bariatric surgery Rijnstate and Radboudumc neuroimaging and Cognition in Obesity) study. Longitudinal analyses revealed decreased Stroop-related activation in the caudate nucleus and the left insula following surgery. These activation changes were accompanied by inflammation-related changes in functional coupling with medial superior frontal regions. Specifically, greater post-surgery decreases in leptin (pro-inflammatory) were associated with decreased connectivity between the anterior insula and the medial superior frontal regions, while increases in macrophage migration inhibitory factor (MIF, potentially neuroprotective) were linked to enhanced connectivity between the caudate nucleus and the medial superior frontal gyrus. Importantly, improved functional coupling between the caudate nucleus and the medial superior frontal gyrus was predictive of better task performance. Our findings suggest that surgery-induced reductions in systemic inflammation may improve inhibitory control in individuals with obesity by promoting neural changes in inflammation-sensitive brain regions and their functional interactions.

This protocol was prospectively registered with the Dutch Trial Register Onderzoekmetmensen.nl, with trial number NTR29050.