bluuebunny/crossref_metadata_2025 huggingface dataset:
Repeatable selection on large ancestry blocks in an avian hybrid zone
Authors: Blain Stephanie A , Justen Hannah C , Langdon Quinn K , Delmore Kira E
Published: February 2025

Hybrid zones create natural tests of genetic incompatibilities by combining loci from two species in the same genetic background in the wild, making them useful for identifying loci involved in both intrinsic and ecological (extrinsic) isolation. Two Swainson’s thrush subspecies form a hybrid zone in western North America. These coastal and inland subspecies exhibit dramatic differences in migration routes; their hybrids exhibit poor migratory survival, suggesting that ecological incompatibilities maintain this zone. We used a panel of ancestry informative markers to identify repeated patterns of selection and introgression across four hybrid populations that span the entire length of the Swainson’s thrush hybrid zone. Two repeatable patterns consistent with selection against incompatibilities – steep genomic clines and few transitions between ancestry states – were found in large genetic blocks on chromosomes 1 and 5. The block on chromosome 1 showed evidence for inland subspecies introgression while the block on chromosome 5 exhibited coastal subspecies introgression. Some regions previously associated with migratory phenotypes, including migratory orientation, or exhibiting misexpression between the subspecies exhibited signatures of selection in the hybrid zone. Both selection and introgression across the genome were shaped by genomic structural features and evolutionary history, with stronger selection and reduced introgression in regions of low recombination, high subspecies differentiation, positive selection within the subspecies, and on macrochromosomes. Cumulatively, these results suggest that linkage among loci interacts with divergent selection and past divergent evolution between species to strengthen barriers to gene flow within hybrid zones.
Efficacy of Dietary Supplementation in the Relief of Inflammatory Bowel Disease: A Systematic Review of Animal Studies
Authors: Mulinari Turin de Oliveira Natalia , Schiebel Carolina Silva , Sauruk da Silva Karien , de Mello Braga Lara Luisa Valerio , Bach Camila , Maria-Ferreira Daniele
Published: February 2025

Context

Supplementation with dietary components is a promising approach for the treatment of inflammatory bowel disease (IBD).

Objective

The aim was to examine the effects of dietary supplements on experimental animal models of IBD.

Data Sources

Articles were selected from 2016 to 2021 and from specific databases (PubMed, Embase, and Scopus).

Data Extraction

Forty-nine studies were analyzed.

Data Analysis

Of the 49 studies, 8 investigated supplementation with oils/polyunsaturated fatty acids, 5 with flavones, 5 with prebiotics and probiotics, 6 with amino acids, 4 with fruits, 4 with vegetables, 2 with minerals, 2 with vitamins, 3 with plants, 2 with polyphenols, and 8 from various sources. Polyunsaturated fatty acids, flavones, prebiotics, and probiotics are among the most extensively studied compounds. Protection is associated with reducing inflammation and oxidative stress, protecting the epithelial barrier and altering the microbiota; however, more rigorous protocols are needed to definitively confirm their protective effects and enable translational research. Fruits, vegetables, plant compounds, minerals, vitamins, and polyphenols, on the other hand, should be studied further and deserve more attention in research.

Conclusion

The results included here support further research into the beneficial effects of supplementation in IBD. Some studies are more advanced and have presented more elaborate protocols, while others still require an increase in knowledge. The identification of dietary supplements that can improve the course of IBD could have an important and lasting impact on the treatment of IBD.

Systematic Review Registration

PROSPERO registration no. CRD42022295260.
Metformin treatment and Immune Reconstitution in People Living with HIV and Type 2 Diabetes: A Matched Retrospective Study
Authors: Bäckdahl Tintin , Hedberg Pontus , Vesterbacka Jan , Carlander Christina , Sönnerborg Anders , Nowak Piotr
Published: February 2025

Background

Despite effective antiretroviral treatment (ART), HIV infection is associated with immune dysfunction and inflammation. Metformin has shown beneficial immunological and anti-inflammatory effects, including in people living with HIV (PLWH). We studied the potential association between metformin treatment and immune reconstitution in PLWH.

Methods

We conducted a retrospective cohort study set in Stockholm, Sweden. PLWH with T2DM that initiated metformin treatment after at least 2 years on effective ART (exposed individuals) and metformin-naïve PLWH (controls) were matched in a 1:1 ratio based on age, sex, baseline immune status and duration of ART. Outcomes included mean values of CD4 cell counts and CD4/CD8 ratios from 1.5 year to 3.5 years after compared with 2 years before the exposed individual started metformin treatment (index date).

Results

Among 1,332 PLWH, 43 metformin exposed individuals (median age 48 years, 11 years since start of ART) with T2DM and 43 non-diabetic controls (median age 47 years, 11 years since start of ART) were included in the matched analyses. The median (interquartile range) change in CD4 T cell count was 35 (-21 to 125) cells/μL among exposed individuals and 48 (-18 to 100) cells/μL among controls (P=0.96). The corresponding numbers were 0.10 (0.03 to 0.20) and 0.08 (0.02 to 0.16) for CD4/CD8 ratio (P=0.18). No differences were observed in subgroup analyses of PLWH with low CD4 T cell counts and CD4/CD8 ratios, respectively.

Conclusions

No significant differences in immune reconstitution were observed between metformin treated individuals and matched controls over the 2-year follow-up period.
Atmospheric sulfate aerosol formation enhanced by interfacial anions
Authors: Wang Gehui , Zhang Si , Wu Can , Zhu Tong , Xu Xinbei , Ge Shuangshuang , Sun Haitao , Sun Zhenrong , Wang Jiaxin , Ji Yuemeng , Gao Jian , Ren Yanqin , Li Hong , Zhang Fang , Wang Yuan , Seinfeld John H
Published: February 2025

Heterogeneous oxidation of SO2 by NO2 on aerosols has recently been found to be one of the major formation pathways of sulfate in polluted troposphere, but the chemical mechanisms and kinetics remain uncertain. By combining lab experiments, theoretical chemistry calculations and field measurements, here we show that the SO2 oxidation by NO2 is critically dependent on anions at the air-aerosol aqueous interface. The reaction rate of NO2 with HSO3- (1.1×108–1.6×109 M-1s-1) is more than four orders of magnitude larger than the traditionally held value for the bulk phase due to the abundant occurrence of chloride, nitrate and carboxylic anions at the air-aqueous interface, which remarkably accelerates sulfate formation during China haze periods by enhancing the uptake of NO2 through interfacial electrostatic attraction. Atmospheric models not accounting for this aerosol interfacial process likely produce major misrepresentations of tropospheric sulfate aerosols under polluted conditions.
Remote/hybrid work in flux: work-place/preference mismatch and adaptations
Authors: Fan Wen , Moen Phyllis
Published: February 2025

The COVID-19 pandemic led to an unprecedented employer-driven shift to remote/hybrid work for those whose jobs allow it, but then came retrenchments, forging disjunctures between where one works (remote/hybrid or in-person) and individual preferences, which we term work-place mismatch. We draw on a combined worker power, employer biases, and adaptive strategy theoretical framing to investigate work-place mismatch in light of remarkable pandemic-precipitated shifts in place of work, opening up possibilities (and preferences) for remote/hybrid arrangements. In addition to examining inequities in work-place mismatch, we theorize employees’ possible adaptive strategies when confronting such mismatch—shifting where they work, changing their locational preferences, or intending to leave or actually leaving their employer. Using a nationally representative four-wave panel (October 2020–April 2022) of US employees who worked fully or partially remotely during the pandemic, we find that work-place mismatch is widespread, especially among those returning to on-site work. Hispanics, Black men, and those lacking a college degree are most likely to experience unfulfilled interest (mismatch) in remote work. Structurally disadvantaged mismatched workers also experience constrained strategies—less apt to change their work location or quit relative to white or college-educated workers.
Low-dose anlotinib plus immune checkpoint inhibitors offers better efficacy and safety in advanced non-small cell lung cancer treatment
Authors: Tan Tingfei , Yuan Siyu , Chu Weiwei , Jiang Jiemei , Chen Meiling , Xia Quan , Wang Junping
Published: February 2025

The combination of anlotinib with immune checkpoint inhibitors (ICIs) has become a common treatment modality in clinical practice. However, the optimal dose of anlotinib to use remains unclear. We collected patients with advanced non-small cell lung cancer (NSCLC) who received programmed cell death-1 blockade combined with different dose of anlotinib as second-line or later line therapy. Subsequently, the efficacy and safety of the combination therapy as well as subgroup analyses of different doses of anlotinib were analyzed. Cox regression was performed to analyze significant factors correlated with progression-free survival (PFS) and overall survival (OS). A total of 50 eligible patients with NSCLC who received anlotinib combined with ICIs therapy were included, of which 27 received low-dose anlotinib (8 mg), and 23 were administered high-dose anlotinib (12 mg). The median PFS (mPFS) and the median OS (mOS) for all patients were 8.3 months [95% confidence interval (CI): 6.3–10.3] and 17.6 months (95% CI: 16.5–18.7), respectively. Subgroup analyses showed that patients treated with 8 mg of anlotinib plus ICIs had significantly longer mPFS than those treated with 12 mg of anlotinib plus ICIs (8.7 vs 6.7 months, P = 0.016). The overall incidence of adverse events was 68.0%, and the most common adverse events of all grades were hypertension. Meanwhile, the incidence of adverse events was higher for 12 mg of anlotinib plus ICIs than that of 8 mg of anlotinib plus ICIs (82.6 vs 55.6%, P = 0.041). Low-dose anlotinib in combination with ICIs for advanced NSCLC may be an effective and well-tolerated option.
Alternative Splicing in Embryo Implantation
Authors: Yu Luping , Zhu Sijing , Bao Haili , Kong Shuangbo
Published: February 2025

Alternative splicing (AS) is a crucial process that produces functionally distinct proteins from a single gene, depending on the developmental or physiological state of cells in multicellular organisms. It plays a significant role in cellular proliferation, survival, and differentiation, including embryonic development, spermatogenesis, and a broad spectrum of diseases. However, the precise involvement of AS in embryo implantation is still unclear. In this review, we summarize the potential roles of AS in regulating mesenchymal-epithelial transitions during embryo implantation, specifically in epithelium regeneration and decidualization initiation via the mesenchymal-epithelial transformation process. Overall, this review emphasizes the impact of AS and splicing variants on embryo implantation and offers novel insights into the potential application of alternative splicing in the treatment of female infertility.
Advancements in elucidating the mechanisms of sorafenib resistance in hepatocellular carcinoma
Authors: Huang Chen , Li Yangqian , Zhang Fengmei , Zhang Chenliang , Ding Zhenyu
Published: February 2025

Primary liver cancer is a major global health challenge, of which hepatocellular carcinoma is the most common. For patients with advanced liver cancer, sorafenib is a first-line targeted drug that occupies a dominant position in clinical applications. Sorafenib is a multi-kinase inhibitor commonly used in clinical practice, which can effectively inhibit tumor cell proliferation, promote cell apoptosis and inhibit angiogenesis. However, the emergence of drug resistance has hindered the development of treatment programs, which is an urgent problem to be solved. Recent studies have revealed many mechanisms and influencing factors of sorafenib resistance (such as epigenetic regulation, programmed cell death, metabolic reprogramming and tumor microenvironment changes). This review not only summarizes the above mechanisms, but also summarizes the combined application of sorafenib with other drugs (such as molecular targeted drugs, other anti-angiogenesis drugs, cytotoxic drugs, immunotherapy drugs, etc.). Finally, potential strategies and research directions to overcome drug resistance (such as targeting epigenetic pathways or metabolic reprogramming) are discussed to provide suggestions for future in-depth research and clinical applications.
Myopia in Houston optometry graduates from 2013 to 2023
Authors: Lal Barsha , Joseph Joshua , Cantrell Amy , Cheng Han , Ostrin Lisa A.
Published: February 2025

SIGNIFICANCE

Adult onset and progression of myopia are not well understood. It is of interest to better characterize myopia progression in young adults, who are frequently subjected to risk factors, such as intense near-work demands.

PURPOSE

This study aimed to assess the prevalence and progression of myopia and other refractive errors in optometry students in the United States.

METHODS

This study was a retrospective chart review of electronic medical records of students enrolled in the optometry program at the University of Houston College of Optometry who graduated between 2013 and 2023. For each student, refractive error was noted from the medical record for eye examinations during their time as an optometry student. Exclusion criteria were ocular disease, myopia control treatment, or refractive surgery. Prevalences of hyperopia (≥+ 0.50 D), emmetropia (>−0.50 to <+0.50 D), myopia (≤−0.50 D), astigmatism (>0.50 D), and anisometropia (≥1.0 D) were determined from spherical equivalent refraction (SER) of the right eye. Absolute and annualized differences in SER were calculated between visits.

RESULTS

Records for 1071 students were reviewed, and 961 were included. Prevalences were 80.7% for myopia, 14.9% for emmetropia, and 4.4% for hyperopia. Additionally, 38.4% had astigmatism, and 16.1% had anisometropia. Students with one follow-up exam (n = 639) showed a significant negative change in SER of −0.05 ± 0.38 D over an average follow-up period of 1.60 ± 0.61 years (p=0.001). Myopia onset was observed in 15.7% of emmetropes at baseline. Greater negative SER change was associated with greater follow-up duration and younger age. Hyperopes and emmetropes did not demonstrate significant changes in SER. An annualized negative SER change of ≥−0.25 D was noted in 20% of the 639 students, of which 5.5% showed ≥−0.50 D.

CONCLUSIONS

Findings demonstrate a high prevalence of myopia among optometry students. A small but statistically significant myopic change in refraction was observed. These findings may implicate a role of education and near work in myopia.
Psycho-oncology clinicians' perceptions of blended psychological therapy for the treatment of anxiety and depression in patients with cancer: a qualitative interview study
Authors: Nunes-Zlotkowski Kelly F. , Shepherd Heather L. , Butow Phyllis , Beatty Lisa , Shaw Joanne M.
Published: February 2025

Background:

Despite effective cancer-specific interventions for depression and anxiety, treatment uptake is low. Blended psychological therapy (BT) may improve access to treatment and enhance uptake and adherence as it combines patient-driven, online therapy with therapist-facilitated sessions. Research supports the acceptability and feasibility of BT in a noncancer context, but evidence in psycho-oncology is limited. The aim of this study was to explore psycho-oncology stakeholders' (service managers, psychologists) views on the feasibility and acceptability of BT and potential implementation of BT models into psycho-oncology care in Australia.

Method:

Qualitative, semistructured telephone interviews were conducted with psychologists working clinically with patients with cancer and psycho-oncology service managers. Interviews were analyzed using a framework analysis approach and mapped against the Consolidated Framework for Implementation Research domains.

Results:

Twenty-two clinicians (17 psychologists, 5 managers) were interviewed. An overarching theme of trust was identified, underpinned by 3 themes: (i) influence of system factors on readiness to change; (ii) treatment engagement; (iii) autonomy and empowerment. Participants shared concerns about service over-reliance on the BT digital component but also recognized its potential in expanding service reach. The use of digital technology was perceived as a barrier to patient engagement but also trusted for providing flexible access. In addition, participants voiced concerns regarding duty-of-care and lack of autonomy to deliver therapy but noted that BT could optimize clinician time and resources.

Conclusion:

Overall, BT was feasible and acceptable. Future research will incorporate stakeholders' preferences for and evaluation of a cancer-specific anxiety and depression BT intervention.
Multidisciplinary Surgical Teams for Cranioplasty: Indications and Outcomes at a Single Institution
Authors: Houskamp Ethan J. , Goel Chirag , Nandoliya Khizar R. , Sadagopan Nishanth S. , Chaliparambil Rahul K. , Byrne Kayla , Thirunavu Vineeth , Texakalidis Pavlos , Khan Osaama H. , Brayton John , Masnyk Taras W. , Jordan Sumanas W. , Galiano Robert D. , Sonabend Adam M. , Rosenow Joshua M. , Tate Matthew C. , Jahromi Babak S. , Potts Matthew B. , Dumanian Gregory A. , Chandler James P. , Ellis Marco F. , Magill Stephen T.
Published: February 2025

Cranioplasty is a common surgical procedure to repair skull defects. Due to cranioplasty’s relatively high complication rates, multidisciplinary surgical teams (MSTs) of neurosurgeons and plastic surgeons have been suggested to improve patient outcomes. However, indications for MST remain undefined. To investigate when MSTs are used for cranioplasty and report patient population differences and outcomes compared with solo neurosurgeons (SN), a retrospective cohort study was performed at a single institution. Of 355 cranioplasties, 268 (75.5%) were performed by SN and 87 (24.5%) by a MST. Cranioplasty cases completed by MSTs had more prior surgeries (P<0.001) and prior infectious etiology (P<0.001). Surgery-related complications occurred in 32.2% of cases. Cranioplasty cases completed by MSTs had no difference in overall complication rates compared with SNs (P=0.3360) but were more likely to experience an infectious complication (25.3% versus 10.1%, P<0.0001) and hydrocephalus (10.3% versus 3.0%, P=0.0091). Overall complication rates did not differ by cranioplasty implant type (P=0.4837) or timing (P=0.3921). The study was limited by selection bias. In conclusion, in this series MSTs were used in higher risk patients with more prior operations and infectious etiology, likely underlying the increased rate of infection and hydrocephalus. The results add to a growing literature supporting the use of MSTs for cranioplasty and raise the question of whether MST can provide better outcomes than SN in simple cranioplasty, which future prospective studies can address.
Longitudinal remote sleep and cognitive research in older adults with mild cognitive impairment and dementia: a prospective feasibility cohort study
Authors: Gabb Victoria Grace , Blackman Jonathan , Morrison Hamish Duncan , Li Haoxuan , Kendrick Adrian , Turner Nicholas , Greenwood Rosemary , Biswas Bijetri , Coulthard Elizabeth
Published: February 2025

STRUCTURED ABSTRACT

INTRODUCTION

We investigated the feasibility of remote longitudinal research using wearable devices and smartphone applications to record sleep and cognition in older adults with mild cognitive impairment (MCI) or dementia.

METHODS

Older adults with MCI or dementia due to Alzheimer’s disease (AD) or Lewy body disease (LBD) and cognitively healthy participants completed at-home sleep and circadian monitoring (digital sleep diaries, actigraphy, wearable sleep electroencephalography (EEG), saliva samples) and digital cognitive assessments for 8 weeks. Feasibility outcomes included recruitment, retention, and data completeness.

RESULTS

41 participants consented (10 AD, 11 LBD, and 20 controls) and 40 completed the 8-week study. Data completeness for sleep EEG was 91% and ranged from 79% to 97% for all remote tasks. 12/40 (30%) participants reported receiving external support with completing study tasks.

DISCUSSION

Longitudinal multimodal sleep and cognitive profiling using novel technology is feasible in older adults with MCI and dementia and healthy older adults.
Utility of genome sequencing and group-enrichment to support splice variant interpretation in Marfan syndrome
Authors: Walker Susan , Bunyan David J. , Thomas Huw B. , Kesim Yesim , Kershaw Christopher J. , Holloway John , Wai Htoo , Day Michael , Smith Cassandra L. , Hawkes Gareth , Wood Andrew R. , Weedon Michael N. , Blair Ed , Curtis Stephanie L. , Fielden Catherine , Evans Julie , Whittington Rebecca , Smithson Sarah F. , Cox Helen , Clift Paul , McEntagart Meriel , Prapa Matina , Alsters Suzanne , Morris-Rosendahl Deborah , Dean John , Morrison Patrick J. , Dixit Abhijit , Sarkar Ajoy , Prescott Katrina , Amel Riazat Kesh Leila , Tharakan Riya , Turner Claire , Ellard Sian , Shaw-Smith Charles , Fasham James , Clowes Virginia , Holden Simon , Somarathi Suresh , Mercer Catherine , Berry Ian , O'Keefe Raymond T. , Banka Siddharth , Baralle Diana , Thomas N. Simon , Baple Emma L. , Taylor Jenny C. , Pagnamenta Alistair T.
Published: February 2025

Purpose: To quantify the impact of non-canonical FBN1 splice site variants in undiagnosed Marfan syndrome (MFS), a connective tissue disorder associated with skeletal abnormalities and Familial Thoracic Aortic Aneurysm Disease (FTAAD). Methods: A systematic analysis of ultra-rare FBN1 variants was performed using genome sequencing data from the 100,000 Genomes Project. Variants were annotated with SpliceAI and the significance of enrichment among individuals with FTAAD was assessed using Fishers exact test. Experimental validation utilised RNAseq, RT-PCR, minigene constructs and replication analysis was with data from UK Biobank. Results: Using aggregate data for 78,195 individuals, we identified 13,864 singleton SNVs in FBN1 of which 21 were predicted to impact splicing (SpliceAI >0.5). Incidence of candidate splice variants in individuals recruited with FTAAD (9/703) was significantly elevated compared with that seen in non-FTAAD participants (12/77,492; OR=84, p=9.7x10-14). Additional analysis uncovered a further 14 families harbouring 11 different FBN1 splice variants. A total of 20 candidate splice variants in 23 families were identified, of which 70% lay beyond the ±8 splice regions. RNA testing confirmed the predicted splice aberration in 14/20 and for 9/20, pseudoexonization was the likely splicing-anomaly. Conclusion: Our findings indicate that non-canonical splice variants may account for ~3% of families with undiagnosed FTAAD, highlighting the importance of incorporating analysis of introns and confirmatory RNA testing into genetic testing for MFS.
Sleep increases broadband fast oscillations in the epileptic focus of patients with focal cortical dysplasia
Authors: Schwoon Nina , Khazali Mohammad F , Brandt Armin , Dümpelmann Matthias , Hegner Yiwen Li , Roehri Nicolas , Altenmüller Dirk-Matthias , Antonio-Arce Victoria San , Reinacher Peter C , Nakagawa Julia M , Doostkam Soroush , Demerath Theo , Urbach Horst , Schulze-Bonhage Andreas , Heers Marcel
Published: February 2025

Rationale

Focal cortical dysplasia (FCD) is associated with increased seizure-risk during sleep, yet the underlying mechanisms remain unclear. Previous studies report increased oscillatory patterns during sleep in focal epilepsy patients with FCD. We investigated whether fast oscillations (FOs, 14-250 Hz) within the epileptic focus significantly change during sleep compared to wake, hypothesizing that analyzing broad frequency bands provides more comprehensive information than narrow bands alone.

Methods

We retrospectively analyzed intracranial EEG recordings from 22 FCD patients (2010-2023), focusing on contacts within the irritative zone (IZ) and seizure onset zone (SOZ). Using semiautomated detections, we compared FO rates between one-hour wake and sleep epochs across beta (14-40 Hz), gamma (40-80 Hz), and ripple (80-250 Hz) bands. Distance-based Multivariate Analysis of Variance (MANOVA) was applied to integrate the spatial organization of FO changes, enabling simultaneous analysis of individual and combined broadband ranges (BGR) while accounting for neocortical detection rates outside the epileptic focus and eloquent cortex.

Results

Analysis of 67 ± 28 (median ± standard deviation) bipolar iEEG contact pairs per patient (SOZ: 14 ± 12, IZ: 29 ± 16) revealed distinct sleep-related patterns. In the SOZ, gamma showed significant increases in 10 patients, followed by BGR in seven patients. The IZ exhibited strong changes in both BGR and gamma (13 patients each) with high concordance (12 matches). Beta and ripple bands showed moderate concordance. Notably, gamma oscillation rates in the SOZ specifically increased in patients with sleep-related epilepsy (p < 0.05).

Conclusion

Gamma oscillations showed the most robust sleep-related increases in the SOZ, while both gamma and BGR showed strong changes in the IZ. These findings suggest gamma oscillations, complemented by broadband analysis, may serve as reliable markers for sleep-related changes in FCD patients.

Funding

YLH (LI1904/2-1) and MH (HE6844/3-1; project ID for both: 468174690) were funded by the German Research Foundation (DFG)

Key points

Within the seizure onset zone, gamma band oscillations (40-80 Hz) followed by combined broadband BGR (14-250 Hz) show more frequent significant increases from wake to sleep across patients

Within the irritative zone, gamma band and broadband oscillations BRG show even more frequent increases from wake to sleep across patients

Changes occur simultaneously across multiple frequency bands, supporting the value of multi-band analysis

Gamma oscillation rates within the seizure onset zone significantly increased from wake to sleep in patients with sleep-related epilepsy (p < 0.05)
Can Chinese Herbal Medicine Be Useful in Treatment of Type 2 Diabetes Mellitus? A Systematic Review of Medicinals Used and Clinical Impact
Authors: Finney Anisa , Conboy Lisa
Published: February 2025

Purpose: With Diabetes Mellitus (DM) on the rise, biomedicine has identified its treatment as challenging due to the multitude of interventions necessary for disease management1. Biomedical treatment utilizes a single action approach, placing patients in the care of one specialist at a time. The traditional Chinese Herbal Medical approach can be of great utility to DM patients administered by a single practitioner aiming to address whole body imbalances. This project synthesized available research discussing Chinese Herbal medicine in the treatment of T2DM via PubMed. Methods: Systematic review was used to search PubMed database October 2022-April 2023 leading to eventual retrieved sample of 30 articles. Search terms includedChinese MedicineANDDiabetes MellitusORChinese MedicineANDType 2 Diabeteswith the filters of clinical trial, open access, in English. Results: Thirty articles met the inclusion criteria and were included in this review. Chinese herbal medicines have been extensively researched appearing in multiple forms such as pills, single herbs, granules, and decoctions. Of the 30 studies, the most reported outcomes were reduced fasting blood glucose, reduced HbA1c, and improved glycemic control. Conclusions: Further research is necessary to capture the role of Chinese herbal medicine in the integrative treatment of T2DM patients.
Multi-Modal Disentanglement of Spatial Transcriptomics and Histopathology Imaging
Authors: Maan Hassaan , Ji Zongliang , Sicheri Elliot , Tan Tiak Ju , Selega Alina , Gonzalez Ricardo , Krishnan Rahul G. , Wang Bo , Campbell Kieran R.
Published: February 2025

Spatially-resolved expression profiling data has revolutionized biological research with multiple emerging clinical applications. Spatial transcriptomic assays are often jointly measured with histopathology imaging data, which is frequently used for diagnosing and staging various diseases. However, determining the extent to which the spatial transcriptomic and histopathology data represent overlapping or unique sources of variation is challenging, particularly given the myriad of factors influencing both, including expression variation, spatial context, tissue morphology, and batch effects. Here, we view this challenge as multi-modal disentanglement and develop an evaluation framework. We introduce SpatialDIVA, a disentanglement technique for jointly measured spatially resolved transcriptomics and histopathology data. We demonstrate that SpatialDIVA outperforms baseline techniques in disentangling salient factors of variation in curated pathologist-annotated multi-sample colorectal and pancreatic cancer cohorts. Further, SpatialDIVA removes batch effects from multi-modal data, allows for factor covariance analysis, and yields actionable biological insights through a novel conditional multi-modal generation method. The SpatialDIVA model, evaluation code, and datasets are available athttps://github.com/hsmaan/SpatialDIVA.
Controlling the Formation of Multiple Condensates in the Synapse
Authors: Safari Nahid , do Rego Barros Fernandes Lima Maria Augusta , Rossetto Riccardo , Zwicker David , D’Este Elisa , Tetzlaff Christian
Published: February 2025

The postsynaptic density (PSD) is a molecule rich structure that continuously adapts its organization controlling synaptic physiology and transmission. Experimental studies have shown that this organization is dominated by the formation of condensates or (nano)clusters and by the seamless transition in their numbers as response to synaptic plasticity. In this study, we utilize different computational modeling frameworks to show that variations in the level of local protein concentrations together with the modulation of protein binding strengths can be key molecular factors in controlling the formation and number of clusters in the synapse. Comparison to MINFLUX data of spatial localization of PSD95 in the postsynapse under different activity conditions allowed us to derive predictions about the correlation between these two factors across a population of synapses. Co-variations of the factors, to mimic a simple LTP protocol, shows that a PSD containing a single cluster can reorganize to form multiple clusters that persists for long periods of time, providing a potential explanation of recent experimental data of PSD reorganization.
Chromatin retained MUSHER lncRNA integrates ABA and DOG1 signalling pathways to enhance Arabidopsis seeds dormancy.
Authors: Sacharowski Sebastian , Krzyszton Michal , Brzezniak Lien , Rogowski Karol Jerzy , Montez Miguel , Rosol Katarzyna , Wrona Magdalena , Yatusevich Ruslan , Manjunath Veena Halale , Szewc Lukasz , Jarmolowski Artur , Swiezewski Szymon
Published: February 2025

Many plant lncRNAs regulate gene expression by binding to chromatin, but how they are retained at the target loci is unclear. We identify a new, chromatin-localized lncRNA - MUSHER, which activates two parallel regulatory pathways to increase Arabidopsis seed dormancy. MUSHER is upregulated in response to high temperatures, contributing to the induction of secondary dormancy. It promotes DOG1 expression by recruitment of the CPSF complex to enhance the proximal cleavage and polyadenylation at the DOG1 gene. It also increases ABA sensitivity in seeds by activating PIR1 gene transcription. These genes, located on different chromosomes, are both bound by MUSHER, despite lacking sequence homology. The chromatin association of MUSHER enables the integration of the DOG1- and ABA pathways to adjust seed germination timing. Additionally, MUSHER and other lncRNAs interact with U1 snRNP, which is required for their chromatin localisation, revealing a novel function of U1 snRNP in plants.
High-throughput MicroED for probing ion channel dynamics
Authors: Gallenito Marc J , Clabbers Max TB , Lin Jieye , Hattne Johan , Gonen Tamir
Published: February 2025

Ion channels play a crucial role in ion transport and are integral to fundamental physiological processes. Therefore, understanding channel structures is essential for elucidating the mechanisms of ion permeation and selectivity beyond what can be predicted by computational simulations. Visualizing dynamics at high resolution, however, remains a significant challenge by structural techniques. In this study, we apply high-throughput Microcrystal Electron Diffraction (MicroED) to explore the structural dynamics of two ion channels, the non-selective ion channel NaK and its mutant, NaK2CNG. This approach utilizes automated data collection and processing to capture distinct structural substates from a large number of microcrystals, offering a deeper understanding of ion channel mechanisms. From a subset of NaK structures, we observed consistent sodium binding at specific sites. In contrast, NaK2CNG appears more dynamic and undergoes dilation of the selectivity filter upon potassium binding. Further, the conduction state of NaK2CNG appears to be influenced by channel gating. Comparative analysis of these structures reveals that non-selectivity arises from the plasticity of the selectivity filter, allowing dynamic control over ion passage. These studies, demonstrate the potential to employ high-throughput MicroED as a technique to address persistent questions regarding ion channel permeation, complementing current computational molecular dynamics studies. We anticipate that this approach will enhance future computational models, leading to more accurate predictions of ion channel behavior and providing a more comprehensive view of transport dynamics.
Bioinformatics analysis identifies sequence determinants of enzymatic activity for the PHARC associated lipase ABHD12
Authors: Chakraborty Arnab , Devarajan Archit , Kumar Kundan , Rohith C. S. , Madhusudhan M. S. , Ratnaparkhi Girish S. , Kamat Siddhesh S.
Published: February 2025

In humans, PHARC (polyneuropathy,hearing loss,ataxia,retinitis pigmentosa, andcataract) is an early onset autosomal recessive neurological disorder caused by deleterious mutations to ABHD12 (α/β-hydrolase domain protein # 12). Biochemically, ABHD12 functions as a lipase, and catalyzes the hydrolysis of lysophosphatidylserine (lyso-PS) (lyso-PS lipase). By doing so, it controls the concentrations and signaling pathways regulated by this potent signaling lysophospholipid in the mammalian brain. While genetic mapping efforts have identified over 30 mutations in ABHD12 from human PHARC subjects, the biochemical activity of these pathogenic mutants remains unknown. To understand this, here, we performed an exhaustive bioinformatics survey, and collated ABHD12 protein sequences from various organisms across evolution. Next, based on sequence alignments and structural modeling, we identified functionally relevant conserved residues in the ABHD12 protein sequence that are potentially important for its enzymatic activity. To validate thesein silicofindings, we generated numerous mutants of murine ABHD12, including those associated with human PHARC subjects, and assayed them for their enzymatic activity. Taken together, these complementaryin silicoand biochemical studies provide the first thorough sequence-function relationship for mammalian ABHD12, especially relevant in the context of PHARC. Finally, our evolutionary analysis identified CG15111 as an ABHD12 ortholog in the fruit fly (Drosophila melanogaster), and enzymatic assays indeed confirmed that recombinant CG15111 has robust lyso-PS lipase activity. Flies serve as an excellent animal system to model various human neurological diseases, and the identification of CG15111 as aDrosophila melanogasterABHD12 ortholog opens new avenues to study PHARC in fly models.
RESiLIENT (Resilience Enhancement with Smartphone in LIving ENvironmenTs) Trial: The Statistical Analysis Plan for 1-year follow-up data
Authors: Noma Hisashi , Furukawa Toshi A. , Tajika Aran , Toyomoto Rie , Sakata Masatsugu , Luo Yan , Horikoshi Masaru , Akechi Tatsuo , Kawakami Norito , Nakayama Takeo , Kondo Naoki , Fukuma Shingo , Christensen Helen , Kessler Ronald C. , Cuijpers Pim , Wason James
Published: February 2025

The RESiLIENT (Resilience Enhancement with Smartphone in LIving ENvironmenTs) trial is designed as a master protocol study including four 2×2 factorial trials to assess specific efficacies of five cognitive-behavioural therapy (CBT) skills (cognitive restructuring, behavioural activation, problem-solving, assertion training, and behavior therapy for insomnia) using the internet CBT program (BMJ Open 2023;13:e067850). In this document, the statistical analysis plan of 1-year follow-up data of the RESiLIENT trial for the assessments of long-term intervention effects is provided.
Interactions between mechanisms of reproductive isolation
Authors: Blanckaert Alexandre , Sousa Vitor C.
Published: February 2025

Speciation is responsible for the diversity of species observed today and corresponds to the build-up of reproductive isolation between populations. Reproductive isolation can be generated by different mechanisms that have been extensively characterized, yet how their interactions affect speciation remains largely unknown. Here, we explicitly model the interaction of three key mechanisms (local adaptation, mate choice and genetic hybrid incompatibilities) quantifying their relative contribution to the evolution of reproductive isolation. We modeled two populations exchanging migrants using Fisher Geometric Model for local adaptation, phenotype matching for mate choice, and multiple pairs of Bateson-Dobzhansky-Muller Incompatibilities (DMI). All three mechanisms were determined by the same set of loci, creating conditions for interactions between barriers both at the genetic and population levels. We found no cases where the three barriers evolved. Instead, two barriers could evolve depending on the migration rate: either local adaptation and genetic incompatibilities for limited migration, or local adaptation and mate choice for higher migration. Our results showed that local adaptation due to ecological differentiation was the first to evolve and by far the most effective reproductive barrier. Finally, we demonstrated that in a polygenic model, populations could become locally adapted and evolve strict mate choice, yet they would not accumulate incompatibilities provided that there was sufficient gene flow.
Factors Associated with All-cause Mortality and Morbidity of Motorcycle Crash-Related Neurological and Musculoskeletal Injuries: The MOTOR Trial Ancillary Study
Authors: Lule Herman , Mugerwa Micheal , Abio Anne , Oguttu Benson , Kakeeto Andrew , Asiimwe Daniel , Lekuya Harvé Monka , Ssebuufu Robinson , Kyamanywa Patrick , Bärnighausen Till , Wilson Michael Lowery , Posti Jussi P.
Published: February 2025

Introduction

The objective of this study was to examine the factors linked to all-cause mortality and morbidity from neurological and musculoskeletal injuries in motorcycle accidents.

Methods

The study was part of a two-armed, parallel, multi-period, cluster-randomized controlled trial of 1003 motorcycle crash victims. Morbidity was assessed using various scoring systems, and mixed effects regression models were employed for analysis.

Results

90-day all-cause mortality was 9.2% (82/887). Factors associated with mortality included referral-to-discharge >1 hour [OR 4.215 (1.802-9.858),p=.001), Kampala Trauma Score (KTS) ≤6 [OR 7.696 (1.932-30.653),p=.004], GCS 9-12 [OR 3.432 (1.194-9.870),p=.022], GCS ≤8 [OR 6.919 (2.212-21.645),p=.001], intra-axial lesions [OR 78.647 (9.871-626.587),p<.001], extra-axial lesions [OR 11.933 (1.386-102.750),p=.024], skull fracture [OR 11.366, (1.197-107.977),p=.034], and decompressive craniotomy (DC) [OR 0.260 (.095-.706),p=.008).

A proportion of 14.5% had unfavourable Glasgow Outcome Scale (1-3); associated factors included increasing age [OR 1.02, (1.013-1.045,p<.001], multiple injuries [OR 4.559 (1.185-17.531), p=.027], KTS 7-8 [OR 2.755 (1.285-5.906), p=.009], KTS ≤6 [OR 7.551 (2.815-20.255), p=.001], GCS 9-12 [OR 4.07 (1.901-8.719), p=.001], GCS ≤8 [OR 13.779 (5.643-33.645),p<.001], and DC [OR 0.149 (.075-.295),p<.001].

Factors associated with unfavourable patient-reported musculoskeletal outcomes included being married [OR 1.984 (1.322–2.976),p=.001], multiple injuries [OR 1.762, (1.001–3.100),p=.049], and enrolment after the onset of the COVID-19 pandemic [OR 2.095 (1.199–3.659), p=.009].

Conclusions

The key determinants of mortality and adverse neurological and musculoskeletal injury outcomes observed in this study are essential for establishing core outcome sets in future research and predictive models.

Summary of the Key Messages

Existing Knowledge:Motorcycle crashes in low- and middle-income countries represent significant public health issues, exacerbated by low helmet usage and insufficient trauma care resources.

Study Contributions:This MOTOR trial ancillary study investigated factors associated with all-cause mortality and morbidity from motorcycle crashes, emphasizing neurological and musculoskeletal injuries as critical targets for enhancing rural trauma care systems.

Implications for Research, Practice, and Policy:Our findings indicate that the anatomical nature, multiplicity and severity of injuries, referral-dispatch intervals, operative interventions, and COVID-19-related social conditions significantly influence injury outcomes. These factors may serve as a foundational outcome set for benchmarking future clinical trials and trauma registries.
Impacts of a relational leadership development program on psychological sense of community
Authors: Islam Naseeha , Wiederholt Senta G. , Park Brian , Tuepker Anaïs , Uchison Elaine Waller , Gordon Leah , Lewis Matthew , Mansour Alexander , Steckler Nicole A. , Edwards Samuel T.
Published: February 2025

Introduction

In a time of increasing employee dissatisfaction and burnout within healthcare, relational leadership approaches have the potential to improve belonging and a sense of community among the workforce.

Methods

The Relational Leadership Institute (RLI) teaches a relationship-based leadership model to help participants enhance interpersonal skills in the healthcare workplace. A survey was conducted of participants to assess their psychological sense of community (PSOC) throughout this leadership program, at baseline, post-program, and 6-months post-program.

Results

Overall mean PSOC was 4.87 (SD 0.68) at baseline, 5.16 (SD 0.77) post-program, and 5.13 (SD 0.72) 6-months post-program, with a significant increase from baseline to post-program (p<0.01) and baseline to 6-months post-program (p=0.01). There was no significant difference between post-program and 6-months post-program PSOC levels (p=0.99). Baseline mean PSOC score was greater among non-white participants (mean 5.00 vs. 4.83 among white participants, p<0.01), and greater among trainees than among working professionals (mean 4.96 vs. 4.82, p<0.01).

Conclusion

The RLI intervention has a significant impact on the psychological sense of community among participants, suggesting that similar relationship-based programs could support today’s healthcare workforce.
Effect of the Gut Microbiome on the reduction of uremic toxins in patients with chronic kidney disease: A systematic review & Network meta-analysis
Authors: Cedillo-Flores Renata , Cuevas-Budhart Miguel Angel , Cavero Redondo Iván , Kappes Maria Soledad , Ávila Marcela , Paniagua Ramón
Published: February 2025

Introduction

Chronic kidney disease (CKD) is associated with increased intestinal barrier permeability, leading to heightened inflammation and oxidative stress. These changes contribute to complications such as cardiovascular disease, anemia, altered mineral metabolism, and CKD progression. Interventions using prebiotics, probiotics, and synbiotics may help mitigate dysbiosis and improve intestinal barrier function.

Aim

This study conducted a network meta-analysis to evaluate the effectiveness of probiotics, prebiotics, and synbiotics in reducing uremic toxins produced by the gut microbiota in CKD patients.

Method

A systematic review and network meta-analysis of randomized clinical trials (RCTs) was performed. The analysis focused on the use of prebiotics, probiotics, and synbiotics in CKD patients at stages 3 to 5, as per KDIGO guidelines, and their association with reductions in uremic toxins such as indoxyl sulfate (IS), p-cresyl sulfate (pCS), urea, and creatinine. The study follows the PRISMA statement.

Results

The studies included 331 patients, primarily male, across CKD stages 3a to 5. The interventions showed a positive impact on the gut microbiota composition, leading to reductions in both free and total p-cresyl sulfate and indoxyl sulfate.

Conclusion

The findings suggest that modulating the gut microbiota through these interventions can effectively reduce specific uremic toxins. However, further trials are necessary to better understand the microbiota modulation and its impact on intestinal bacterial composition.

PROSPERO Registration

CRD42023438901
Sexual health empowerment interventions for migrant women: a systematic review of the literature
Authors: Ouanhnon Lisa , Daumail Laure , Kerihuel Marie , Palmaro Aurore , Dupouy Julie , Durand Marie-Anne
Published: February 2025

Introduction

Migrant women are suffering from inequalities in access to care and prevention, quality of care, and in particular, sexual health care. As part of an overall project to develop a primary care intervention aimed at empowering migrant women in sexual health, the first objective will be to review the characteristics of sexual health empowerment interventions targeting migrant women. The second objective will be to assess the effectiveness of these interventions.

Methods and analysis

A systematic review will be conducted across PubMed, Cochrane, Embase, Psychinfo/ Psycharticles, Web of science, Cairn, as well as grey literature, from inception until 01/01/2023. We will include randomized clinical trials, quasi-experimental, and qualitative studies published in any language before 01/01/2023, assessing the effect of a sexual health empowerment intervention targeted at migrant women and meeting the selection criteria. Screening of articles and data extraction will be conducted by two independent researchers. Disagreements will be resolved by a third reviewer. The quality of all included studies will be assessed using validated tools according to the study design. Results will be reported using the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidlines, and a narrative synthesis will be conducted.

Ethics and diffusion

This systematic review will involve only secondary data, so ethical approval was not required for this study. The results will be disseminated in peer-reviewed journals and conferences.