bluuebunny/crossref_metadata_2025 huggingface dataset:
Colorectal cancer progression to metastasis is associated with dynamic genome-wide biphasic 5-hydroxymethylcytosine accumulation
Authors: Murcott Ben , Honig Floris , Halliwell Dominic Oliver , Tian Yuan , Robson James Lawrence , Manasterski Piotr , Pinnell Jennifer , Dix-Peek Thérèse , Uribe-Lewis Santiago , Ibrahim Ashraf EK , Sero Julia , Gurovich David , Nikolai Nikolas , Murrell Adele
Published: February 2025

Background

Colorectal cancer (CRC) progression from adenoma to adenocarcinoma is associated with global reduction in 5-methylcytosine (5mC) and 5-hydroxymethylcytosine (5hmC). DNA hypomethylation continues upon liver metastasis. Here we examine 5hmC changes upon progression to liver metastasis.

Results

5hmC is increased in metastatic liver tissue relative to the primary colon tumour and expression of TET2 and TET3 is negatively correlated with risk for metastasis in patients with CRC. Genes associated with increased 5-hydroxymethylcytosine show KEGG enrichment for adherens junctions, cytoskeleton and cell migration around a core cadherin (CDH2) network. Overall, the 5-hydroxymethylcyosine profile in the liver metastasis is similar to normal colon appearing to recover at many loci where it was originally present in normal colon and then spreading to adjacent sites. The underlying sequences at the recover and spread regions are enriched for SALL4, ZNF770, ZNF121 and PAX5 transcription factor binding sites. Finally, we show in a zebrafish migration assay using SW480 CRISPR-engineered TET knockout and rescue cells that reduced TET expression leads to a reduced migration frequency.

Conclusion

Together these results suggest a biphasic trajectory for 5-hydroxymethyation dynamics that has bearing on potential therapeutic interventions aimed at manipulating 5-hydroxymethylcytosine levels.
Reconstructed Cell-Type Specific Rhythms in Human Brain link Alzheimer’s Pathology, Circadian Stress, and Ribosomal Disruption
Authors: Hollis Henry C. , Sharma Ashish , Sheehan Patrick W. , Maggi Leonard B. , Weber Jason D. , Hammarlund Jan A. , Bennet David A. , Menon Vilas , Musiek Erik S. , Anafi Ron C.
Published: February 2025

Alzheimer’s disease (AD) disrupts behavioral circadian rhythms, but its effects on molecular rhythms in the human brain are poorly understood. Using single-nucleus RNA sequencing from post-mortem cortical samples, we informatically estimated the relative circadian phases of 409 persons with and without AD dementia. We then reconstructed circadian expression profiles across cell types. While core clock rhythms were preserved in AD, many cell-type specific circadian outputs were disrupted. Rhythms in ribosomal biogenesis and oxidative phosphorylation were dampened across cell types. Similar losses in ribosomal gene expression rhythms were observed in APP/PS1 mice, which showed further reductions in ribosomal protein expression and polysome-mediated translation after circadian desynchrony. Exploratory computational modeling reveals that altered translation may contribute to the increased circadian variability seen in AD patients. These findings reveal altered cell-type specific circadian output rhythms in the brains of AD affected patients, and highlight disrupted ribosomal rhythms as a feature of AD.
The economic strategies of superorganisms
Authors: Leahy Lily , Riskas Hannah L. , Halliwell Ben , Wright Ian J. , Carlesso Amelia G. , Sanders Nathan J. , Bishop Tom R. , Parr Catherine L. , Chown Steven L. , Andersen Alan N. , Gibb Heloise
Published: February 2025

Economic principles can be applied to biological life to understand how resource allocation strategies maximise evolutionary fitness1. This approach has been applied in plants under the global slow-fast leaf economic spectrum which describes investment and return of carbon and nutrients in leaves1. Whether this applies to other taxa, indicating general principles, remains untested. We advance generality in economic theories of life by showing that a slow-fast spectrum captures the resource economics of a globally dominant group of superorganisms, the ants. Like plants, ants acquire resources through modular units, the workers. Here, we collect traits from ant workers of 123 species across large-scale environmental gradients. Ants trade-off investment in biomass, chemical elements (nitrogen, phosphorus), energy (metabolic rate) and worker number, against assimilation rates (resource revenue) and lifespan. This superorganism economic spectrum does not vary across environmental gradients, rather, both slow and fast strategies persist amongst co-occurring species. High phylogenetic conservatism suggests early lineages of ants diverged in their economic strategies and subsequently diversified, locking in fundamental templates of investment and resource return. The remarkable similarities in economic strategies employed by ants and plants for resource acquisition and use suggest that there may be common principles underlying the rules of life.
Effect of surgical approach to hip arthroplasty on postoperative pain and mobilization and on efficacy of intrathecal oxytocin for pain
Authors: Shields John S , Ijebuonwu Chiamaka , Korn Elizabeth G , Mueller Ariel , Houle Timothy T , Langfitt Maxwell K , Pollock David C , Eisenach James C ,   Spinal Oxytocin Hip Surgery Collaborators
Published: February 2025

Objective: Compare the effect of posterior surgical approach (PA) vs direct anterior approach (DAA) on speed of recovery from pain and dysfunction and on intrathecal oxytocin analgesia after total hip arthroplasty (THA). Study design: Nested cohort within a randomized, controlled, double-blind trial Setting: Hospital Subjects: Individuals aged 31 to 80 years undergoing total hip arthroplasty (THA) Methods: In this secondary analysis of a randomized controlled trial, the association between surgical approach and number of daily steps was assessed, and whether this was modified by receipt of intrathecal oxytocin. Data were collected from accelerometers and daily patient diaries in the first eight weeks postoperatively. Outcomes were analyzed using generalized linear regression models. Results: Ninety patients underwent THA, of which 35 (38.9%) received a PA. Patients were predominantly female (57.8%) with a mean age of 60.6 (standard deviation [SD] 9.3) years. On postoperative day one patients who received a PA with placebo took more steps (mean difference [MD] 53.72, 95% CI: -1717.86, 1825.31) than patients who underwent a DAA. Trajectories were significantly modified by whether they received oxytocin, in which patients who underwent PA with oxytocin took more steps than patients who underwent DAA (p<0.001). Discussion: Further studies are needed to understand mechanisms underlying oxytocin interaction with surgical approach and guide considerations for recovery after THA.
Machine Learning-Driven Glycoproteomic Profiling Identifies Novel Diabetes-Associated Glycosylation Biomarkers.
Authors: Elguoshy Amr , Yamamoto Keiko , Hirao Yoshitoshi Yoshitoshi , Yanagita Kengo , Uchimoto Tomohiro , Kamimura Takashi , Takasawa Tetsuya , Yamamoto Tadashi
Published: February 2025

Glycosylation plays a critical role in protein function and disease progression, including diabetes mellitus. This study performed a comprehensive glycoproteomic analysis comparing healthy volunteers (HV) and DM samples, identifying 19,374 peptides and 2,113 proteins, of which 1,104 were glycosylated. A total of 287 distinct glycans were mapped to 3,722 glycosylated peptides, revealing significant differences in glycosylation patterns between HV and DM samples. Statistical analysis identified 29 significantly altered glycosylation sites, with 23 upregulated in DM and 6 downregulated in DM. Notably, the glycan HexNAc(2)Hex(2)Fuc(1) at position 215 of Prosaposin was significantly upregulated in DM, marking its first reported association with diabetes. Machine learning models, particularly Support Vector Machines (SVM) and Generalized Linear Models (GLM), achieved high classification accuracy (~ 92%: 96%) in distinguishing HV and DM samples based on glycosylation features (Glycans, Glycosylated proteins, and Glycosylation sites). These findings suggest that altered glycosylation patterns may serve as potential biomarkers for diabetes-related pathophysiology and therapeutic targeting.
Characterization of energy filtering slit widths for MicroED data collection
Authors: Clabbers Max T.B. , Hattne Johan , Martynowycz Michael W. , Gonen Tamir
Published: February 2025

A favorable signal-to-noise ratio is essential for obtaining high-quality diffraction data in macromolecular electron crystallography. Inelastic scattering contributes significantly to the noise, reducing contrast between diffraction peaks and background, which complicates peak detection and compromises the accuracy of intensity integration. Energy filtering mitigates these challenges and enhances diffraction data quality by removing the inelastically scattered electrons, leading to reduced background noise and sharper Bragg peaks. Previously, we reported a substantial improvement in MicroED data quality and resolution with energy filtering. Here, we systematically evaluate the impact of different energy filter slit widths for optimal MicroED data collection. Data from proteinase K lamellae were collected using the 5, 10, and 20 eV energy filter slit widths. Our results show that the narrowest slit widths result in a stronger diffraction signal with lower background noise, improving the precision of the intensity measurements which resulted in better structural models. Our findings provide insights into the optimization of energy filter slit settings that, when paired with direct electron detection, enhance MicroED data collection strategies in MicroED by improving the signal-to-noise ratio, supporting higher quality data and ultimately enabling more precise structure determination.
Non-sexual community transmission of mpox clade Ib in DR Congo
Authors: Bugeme Patrick Musole , Bugale Patrick Kazuba , Mukika Trust Faraja , O’Driscoll Megan , Perez-Saez Javier , Bugwaja Levi , Shangula Salomon Mashupe , Kasi Willy , Bengehya Justin , Ngai Stephanie , Carrion Martin Antonio Isidro , Jackson Jules , Katoto Patrick , Bahizire Esto , Mulopo-Mukanya Noella , Lessler Justin , Knee Jackie , Vetter Pauline , Lee Elizabeth C. , Mukadi-Bamuleka Daniel , Azman Andrew S , Malembaka Espoir Bwenge
Published: February 2025

Introduction

In September 2023, mpox clade Ib emerged in Kamituga, a mining zone in South Kivu, DR Congo, primarily through sexual transmission. This study investigates an mpox clade Ib outbreak in Uvira, an urban area 360 km from Kamituga, where the first case was reported in May 2024.

Methods

From June to October 2024, clinical and household data from suspected mpox cases were collected at Uvira hospital and household investigations. Mpox laboratory confirmation was performed via PCR. We analyzed demographic, exposure, and clinical data to characterize putative transmission patterns, severity, and risk factors.

Results

Among 973 suspected cases, 42.7% (415) had PCR results, with 77.6% (n=322) testing positive. The median age of suspected cases was 9 years (IQR: 3–20), with 63.7% under-15 (n=620) and 32.1% under-5 (n=312). Severe cases (≥100 lesions) were more frequent in children under 15 (25.6%, 142/554) than others (16.1%, 49/304; p<0.001). Acute malnutrition affected 12.2% (22/181) of children under-5. The case fatality ratio was 0.7% (7/973), rising to 4% (5/127) in infants under one year. Among HIV-tested individuals, 1.8% (6/329) were HIV-positive. Pregnant women accounted for 14.5% (19/131) of women aged 15-49 years. The vast majority reported exposures to other suspected mpox cases were in the household (67.9%), with limited sexual (6%) or healthcare-related occupational exposures (1.4%). Female sex workers represented 1.2% of cases. Animal exposures were predominantly domestic (97.4%, 38/39).

Conclusion

This child-centered outbreak, driven by non-sexual transmission, underscores the need for pediatric vaccines, nutritional support, and household interventions. Adult-focused responses alone may be insufficient.
Treatment outcomes of tuberculosis among people living with HIV/AIDS: A comparative assessment of primary and tertiary healthcare centres in Nasarawa State, Nigeria
Authors: Aya Benjamin Mari , Salihu Ismail Ndalami , Ahmad Dalhatu Muhammad , Tyem Dinfa Dombin , Mari Ovye Stephen , Alu Namo David , Joseph Benjamin Nasara , Shuaib Faisal
Published: February 2025

One of the Sustainable Development Goals for 2030 is to end the global TB epidemic. Translating this laudable target to reality requires strengthening collaborative tuberculosis/human Immunodeficiency Virus (TB/HIV) care at all levels to end TB in Nigeria. This study assessed the treatment outcomes of TB among people living with HIV (PLWH) and compared the treatment outcomes of TB between primary and tertiary healthcare facilities in Nasarawa State, Nigeria.

This facility-based retrospective survey of TB patients living with HIV was conducted in two tertiary healthcare facilities and a primary healthcare centre (PHC). Records of eligible patients who completed treatment between January 2016 and December 2019 were abstracted using a data pro forma. Treatment outcomes were categorized as either successful or unsuccessful. Descriptive and inferential analyses were conducted, in addition to multivariate logistic regression.

A total of 959 patients with a mean age of 33±14 years were evaluated; there were 847 adults (88.3%), and the proportion of females was 499 (52%). The proportion of patients who completed TB treatment was 26%; 20.5% were cured, while the mortality rate was 9.2%. The treatment success rate (TSR) was 46.5%; tertiary healthcare facilities had the highest unsuccessful treatment rates compared to the PHC. The TSR declined steadily from 68.8% in 2016 to 57.6% in 2019. Being treated at a tertiary healthcare facility (AOR=3.6, CI; 2.0-6.6) predicted successful treatment outcomes of TB among PLWH.

TB’s overall TSR among PLWH was low. Within the outcome categories, the proportion of patients who completed treatment and those cured compared better with unfavourable outcomes. The rate of unsuccessful TB treatment is highest in tertiary healthcare facilities compared to PHC. However, being treated in the tertiary healthcare facility predicted successful treatment outcomes, while treatment failure, death, and loss to follow-up were highest in the tertiary healthcare facilities.
PEQI: A population dietary quality index for developed countries
Authors: Christopoulos Konstantinos , Christou Christina , Eleftheriou Konstantinos , Hassapis Christis
Published: February 2025

Background

While there are numerous dietary quality indices for individuals, a lon-gitudinal population-level index is missing from the literature. This article presents a novel population-level dietary index, the Population Eating Quality Index (PEQI) that measures a country’s annual dietary quality.

Methods

Using data from the Food and Agriculture Organization and the Global Dietary Database, PEQI comprises of ten waste-adjusted food items for which weighted scores are assigned according to their effect on human health. Associations between the PEQI and health outcomes for a panel of developed countries were studied to further validate the instrument.

Results

The index shows good predictive ability regarding life expectancy at birth and premature mortality for an average developed country.

Conclusions

PEQI has multiple potential applications in the ecological study of health and nutrition as an exposure or even as an outcome.
The incubation periods of Monkeypox virus clade Ib
Authors: Perez-Saez Javier , Bugeme Patrick Musole , O’Driscoll Megan , Bugale Patrick Kazuba , Mukika Trust Faraja , Bugwaja Levi , Shangula Salomon Mashupe , Bengehya Justin , Ngai Stephanie , Carrion Martin Antonio Isidro , Jackson Jules , Mulopo-Mukanya Noella , Knee Jackie , Eckerle Isabella , Lee Elizabeth C. , Mukadi-Bamuleka Daniel , Lessler Justin , Azman Andrew S , Malembaka Espoir Bwenge
Published: February 2025

Background

Monkeypox virus (MPXV) clade Ib, first detected in Democratic Republic of the Congo (DRC) in September 2023, spread internationally within months, prompting a WHO emergency declaration. Data on how this clade differs from others, including the incubation period which both shapes outbreak dynamics and informs epidemic response strategies, remain limited.

Methods

We use clinical, laboratory and reported exposure data from suspected and qPCR-confirmed mpox cases in Uvira, DRC to estimate the incubation period for MPXV clade 1b. We developed a Bayesian model to estimate incubation periods of various symptom onset definitions (rash, fever, any symptom), demographic factors and putative transmission route (sexual vs. non-sexual).

Results

Among 92 PCR-confirmed cases, the median incubation period from exposure to rash was 18.6 days (95% CrI: 15.2-22.6). Five percent of cases are expected to develop a rash within 5.4 days (95% CrI; 3.4-7.6) and 95% within 37.6 days (95% CrI: 30.3-47.0). The incubation period differed by putative transmission route: sexual transmission had a shorter median (9.5 days, 95% CrI 3.7-16.4) than non-sexual transmission (18.9 days, 95% CrI: 15.3-23.0).

Conclusions

Incubation periods for clade Ib are longer than previous estimates for other MPXV clades, but vary strongly by sexual vs. non-sexual exposures, the former closely aligning with observations from the predominantly sexually transmitted clade IIa global outbreak. These findings highlight the significant differences by transmission route – likely reflecting differences in infectious viral dose and suggest the need to revise global post-exposure monitoring recommendations.
Re-examining the meningitis belt: associations between environmental factors and epidemic meningitis risk across Africa
Authors: Cliff Molly , Jahn Sally , Fouda Andre Bita , Latt Anderson , Lingani Clement , Trotter Caroline
Published: February 2025

In 2002 Molesworth et al created a logistic regression model to investigate the spatial distribution of meningitis epidemics in Africa and determine geographical risk. We aim to understand if the meningitis belt geography and environmental risk factors have changed in the last 20 years by updating this analysis. Epidemic bacterial meningitis data from 2003-2022 were provided by WHO-AFRO. Districts (ADMN2) across Africa were coded as 1 if they had experienced a meningitis outbreak and 0 if they hadn’t. Environmental data were obtained from open sources. To preserve seasonal climate variation, monthly means of wind speed, rainfall, dust, and humidity were processed into climatic profiles using k-means clustering. Logistic regression was carried out with meningitis epidemic history as the dependent variable and k-means clusters of rainfall, dust, humidity, and windspeed, alongside average land-cover type as the independent variables. A sensitivity analysis was conducted excluding the Democratic Republic of Congo (DRC), due to limited laboratory confirmation of suspected cases. Rainfall, dust, and humidity demonstrated the strongest statistical association with meningitis outbreaks and were included in our final model. With a probability cutoff value of >0.4, our model had a specificity and sensitivity of 81.0% and 84.3% respectively in identifying districts having experienced a meningitis epidemic. With an extended dry season, the Sahelian region had the highest risk of meningitis outbreaks (probability >0.8). The inclusion/exclusion of the DRC had a significant impact on our model. Whilst Republic of the Congo, Gabon, Liberia, and Angola had a moderate risk of meningitis (probability >0.4) within our full model, no countries surrounding the meningitis belt were at risk for outbreaks within the sensitivity analysis. Although our research may suggest a south-westerly expansion of the meningitis belt this is difficult to verify. Surveillance of suspected meningitis cases should be accompanied by laboratory confirmation to improve outbreak definition.
CD4 T cell counts are inversely correlated with anti-cluster A antibodies in antiretroviral therapy-treated PLWH
Authors: Benlarbi Mehdi , Richard Jonathan , Clemente Tommaso , Bourassa Catherine , Tolbert William D. , Gottumukkala Suneetha , Peet Marc-Messier , Medjahed Halima , Pazgier Marzena , Maldarelli Frank , Castagna Antonella , Durand Madeleine , Finzi Andrés
Published: February 2025

While antiretroviral therapy efficiently suppresses viral replication, inflammation and immune dysfunction persist in some people living with HIV-1 (PLWH). Soluble gp120 (sgp120) has been detected in PLWH plasma and its presence is linked to immune dysfunction. It was reported that sgp120 binding to CD4 on uninfected bystander CD4+T cells sensitizes them to antibody-dependent cellular-cytotoxicity (ADCC) mediated by non-neutralizing antibodies present in PLWH plasma. Using three independent PLWH cohorts, we observed that non-neutralizing anti-cluster A antibodies are negatively associated with CD4+T cell counts. Anti-CD4BS antibodies blocked the coating of uninfected bystander cells by sgp120, thereby preventing their elimination by ADCC. Supporting a protective role of anti-CD4BS antibodies, PLWH having these antibodies didn’t show a negative association between CD4 T cell counts and anti-cluster A. Our results reveal that anti-cluster A antibodies are associated with immune dysfunction in PLWH and anti-CD4BS antibodies might have a beneficial impact in these individuals.
Graft-versus-host disease prophylaxis shapes T cell biology and immune reconstitution after hematopoietic cell transplant
Authors: Siegel Steven J. , DeWolf Susan , Schmalz Joseph , Saber Wael , Dong Jiayi , Martens Michael J. , Logan Brent , Albanese Alexandre , Iovino Lorenzo , Chen Edward , Kaminski James , Neuberg Donna , Hebert Kyle , Keskula Paula , Zavistaski Jillian , Steinberg Lea , Schichter Isabella , Cagnin Lorenzo , Hernandez Vanessa , Warren Makya , Applegate Kristy , Bar Merav , Chhabra Saurabh , Choi Sung Won , Clark William , Das Suman , Jenq Robert , Jones Richard J. , Levine John E. , Murthy Hemant , Rashidi Armin , Riches Marcie , Sandhu Karamjeet , Sung Anthony D. , Larkin Karilyn , Al Malki Monzr M. , Gooptu Mahasweta , Elmariah Hany , Alousi Amin , Runaas Lyndsey , Shaffer Brian , Rezvani Andrew , Jurdi Najla El , Loren Alison W. , Scheffey Danielle , Sanders Catherine , Hamadani Mehdi , Dudakov Jarrod , Bien Stephanie , Robins Harlan , Horowitz Mary , Bolaños-Meade Javier , Holtan Shernan , Bhatt Ami S. , Perales Miguel-Angel , Kean Leslie S.
Published: February 2025

Successful hematopoietic cell transplant requires immunosuppression to prevent graft-versus-host disease (GVHD), a lethal, T-cell-mediated post-transplant complication. The phase 3 BMT CTN 1703 trial demonstrated superior GVHD-free/relapse-free survival for post-transplant cyclophosphamide (PT-Cy)-based GVHD prophylaxis versus tacrolimus/methotrexate (Tac/MTX), but did not improve overall survival. To compare T-cell biology between GVHD prophylaxis regimens, 324 patients were co-enrolled onto BMT CTN 1801 (NCT03959241). We quantified T-cell immune reconstitution using multi-modal analysis, including T-cell receptor (TCR) sequencing of 2,359 longitudinal samples (180,432,350 T-cells). Compared to Tac/MTX, PT-Cy was associated with an early, substantial reduction in TCR diversity that was sustained for 2 years. PT-Cy led to a T-cell reconstitution bottleneck, including reduced thymic output and virus-associated TCRs. Decreased D+14 TCR diversity predicted prevention of chronic GVHD, but also correlated with increased moderate-to-severe infections. This study reveals how distinct immunosuppression strategies have significant effects on the global immune repertoire, underpinning post-transplant clinical outcomes.
Gaps in integration of sexual and reproductive health and rights into climate change research in sub-Saharan Africa: A scoping review
Authors: Amadi Jacinter A. , Odwe George , Onyango Francis O. , Kangwana Beth
Published: February 2025

Sub-Saharan Africa is faced with triple challenges of high vulnerability to climate change (CC) impacts, high levels of inequality and poor sexual and reproductive health and rights (SRHR) outcomes. Climate change can worsen SRHR situation for high-risk groups such as women, children, adolescent girls and people living with HIV. This scoping review takes stock of the state of research on the intersection between CC and SRHR in SSA with a view of identifying gaps and opportunities for effective evidence generation and integration in climate actions. The review followed Arksey and O’Malley framework. Data charting was conducted using Population, Exposure, Comparator, Outcome tool in Covidence. Thirty-seven (37) studies were reviewed, 57% were quantitative while 41% and 2% used qualitative and mixed methods respectively. SRHR components investigated include maternal newborn and child health at 43% (n=16), HIV at 19% (n=7), gender-based violence at 11% (n=4), and fertility intentions and outcomes at 11% (n=4). SRHR elements that are under-researched in the context of CC include access to and uptake of contraceptives, post abortion care, harmful practices (child marriages and female genital mutilation), menstrual health, pregnancy losses, bodily autonomy, and (in)fertility. Drought, floods, heat stress and rainfall seasonality have received fair attention in research, yet impacts of climate hazards like tropical cyclones, wildfires and salt-water intrusion are missing in research. There is inadequate research at the intersection of CC and SRHR hindering progress towards climate resilience and attainment of good health and well-being for all. Effective and equitable integration requires that SRHR issues be recognized, and deliberate investments (research, policies, programs, interventions and financing) put in place to address the critical SRHR gaps and climate vulnerabilities to enhance resilience.
Age-Dependent Sex Disparities in Sjogren’s Disease Prevalence Align with Natural Hormone Fluctuations
Authors: Diggins Eliza C. , Weller Melodie L.
Published: February 2025

Sjogren’s Disease (SjD), like many autoimmune diseases, shows a strong female-to-male sex bias, raising the possibility of a hormone-mediated mechanism. However, specific hormonal drivers and the underlying mechanisms remain unclear. In this study, we analyze a electronic health record dataset containing >100,000 SjD patients, allowing for a comprehensive statistical investigation into sex bias and serum hormone levels associated with SjD susceptibility. Focusing on testosterone, estradiol, and sex hormone-binding globulin (SHBG), our analysis reveals an age-dependent trend in SjD’s sex bias, with a substantially reduced female bias observed in pediatric cases. This finding, alongside statistical modeling, suggests that testosterone or estradiol may influence the sex disparity in SjD prevalence, with distinct effects at different life stages. Specifically, we observe a higher percentage of male SjD patients in early childhood (30.06%, [CI: 26.16-34.11]), declining sharply in late pubescence into adulthood (9.85% [CI: 9.51–10.16]), followed by a secondary steady increase in male prevalence among older adults (13.50% [CI: 13.25-13.76]). Our models indicate that these shifts in sex bias align with typical age-related hormonal changes rather than abnormal levels, suggesting that natural hormone fluctuations may play a significant role in modulating disease susceptibility. This research not only refines our understanding of SjD but also underscores the importance of hormone-level monitoring in future SjD studies and potential therapeutic strategies. Advanced studies are required to further clarify whether testosterone or estradiol is the primary mediator of these trends, promising new insights into hormone-linked pathways and autoimmune disease pathogenesis.
Physicians’ Knowledge and Experiences of Counseling on Complementary, Alternative, and Integrative Medicine in Cancer Care: A Qualitative Systematic Review
Authors: Ng Jeremy Y. , Shah Aimun Qadeer , Narr Lana Abu , Qian Alyssa , Cramer Holger
Published: February 2025

Background

Despite the increasing use of complementary, alternative, and integrative medicine (CAIM) use among cancer patients, there remains ambiguity surrounding physicians’ understanding and counseling practices in this area. The objective of this qualitative systematic review was to identify the knowledge and experiences of physicians who counsel patients on CAIM in the context of cancer.

Methods

MEDLINE, EMBASE, and AMED were systematically searched from inception to May 27, 2023. Reference lists of relevant review articles were also hand- searched. Eligible articles contained qualitative data focused on physicians’ perceived knowledge and experience pertaining to CAIM counseling for cancer care. Relevant findings were extracted and analyzed using a narrative synthesis approach to identify key themes and subthemes.

Results

Thirty-five articles were included (30 from database searching and 5 from hand-searching reference lists). Four main themes were identified: lack of knowledge and formal training on CAIM; distrust and concern about CAIM safety and/or efficacy; accepting CAIM as an important part of cancer care; and the communication dynamics between patients and physicians.

Conclusions

This study highlights that physicians recognize CAIM as an important component of person-centered and holistic cancer care; however, they have concerns about the safety and/or efficacy of these therapies. Accordingly, there is a need for improved education for physicians on the safety and effectiveness of CAIMs, to better equip them to effectively counsel patients in this area. Future research exploring the perspectives of medical trainees and other healthcare providers on CAIM for cancer is also warranted.
The effect of a digital health physical activity program integrating gamification for obesity management in comparison to the usual care: a randomized controlled trial with ideographic approach
Authors: Mazeas Alexandre , Chalabaev Aina , Blond Marine , Mourgues Charline , Pereira Bruno , Duclos Martine
Published: February 2025

Digital health interventions and gamification hold promise for managing chronic diseases, but evidence comparing their efficacy to usual care is limited. This two-arm parallel randomized controlled trial with embedded N-of-1 analyses assessed whether a digital intervention integrating gamification and telecoaching (Kiplin) outperform a supervised face-to-face adapted physical activity (PA) program (usual care) in obesity management. Patients with obesity and/or T2D (N = 50, Mage = 46.7 years, 74% female) were randomized to either the Kiplin digital intervention or usual care group, and completed a 3-month program with a 6-month follow-up. The primary outcome was the change in daily step count between baseline and the intervention's end. Secondary outcomes assessed changes in daily steps, PA, quality of life, body composition, and physical capacities over nine months. Mixed-effects models and generative additive models were conducted to analyze both between- and within-person evolutions in PA. A cost-utility analysis was computed to compare the cost-effectiveness of the programs. Compared to the usual care, Kiplin participants showed significant increases in daily steps during the intervention and follow-up periods, with sustained effect sizes. Idiographic analyses revealed variable individual responses, highlighting the need for tailored approaches. No significant differences were observed in secondary clinical outcomes or the cost-utility analysis. This study demonstrates the potential of digital interventions to sustain PA improvements that could offer an alternative to face-to-face programs, but the clinical and economic impacts need to be further evaluated.
Changes in somatic symptoms among people with severe COVID anxiety, before and after the coronavirus pandemic
Authors: Grocott Leila , King Jacob D , Mcquaid Aisling , Leeson Verity C , Crawford Mike J
Published: February 2025

Background Anxiety and somatic symptoms were common during the coronavirus pandemic. People who were highly anxious about COVID-19 may have been at a higher risk of developing new somatic symptoms which persisted after the pandemic. Here we examine changes in somatic symptoms before and after the pandemic among people who had severe COVID anxiety, and identify factors associated with these changes. Design UK adults who met the threshold for severe COVID anxiety were recruited online during the coronavirus pandemic, and were asked to rate their somatic symptoms post-pandemic, and retrospectively before the pandemic with the PHQ-15. Data on demographic and clinical factors were also collected. Methods Descriptive statistics and multiple linear regression were used to characterise the sample of 197 people who provided complete data, and to examine factors associated with changes in somatic symptoms. Results Mean PHQ-15 score increased significantly from 7.97 before the pandemic to 11.34 afterwards (t= 9.043, p<0.001). Despite this, there were gradual corresponding declines in levels of COVID anxiety and other co-occurring mental health symptoms after the pandemic ended. Multiple linear regression models identified that greater generalised anxiety symptoms and living with someone vulnerable to COVID were the strongest predictors of increased somatic symptoms during the pandemic. Conclusions People with severe COVID anxiety reported high rates of somatic symptoms before the pandemic, which then increased significantly after the pandemic. There appears to be a complex interaction between COVID anxiety, pandemic experience, and somatic symptoms which warrants further investigation, and could inform targeted intervention in the future.
The Critical Role of the 2’-OH group in Phase Separation and Percolation Transitions of RNA
Authors: Wadsworth Gable M. , Aierken Dilimulati , Thurston George M. , Joseph Jerelle A. , Banerjee Priya R.
Published: February 2025

Mg2+ion-dependent RNA liquid–liquid phase separation with lower critical solution temperatures is driven by the phosphate backbone and modulated by the solvation property of nucleobases. Here, we report a key role of the 2’-OH group of ribose sugar in RNA condensation in the presence of divalent cations. We show that 2’-deoxyribose inhibits nucleic acid phase separation and suppresses the intra-condensate networking transition, known as percolation, that underlies the condensate dynamical arrest. All-atom simulations reveal increased solvation and compaction of single-stranded DNA compared to RNA, suggesting an unintuitive role of chain flexibility in modulating heat-induced nucleic acid phase separation and percolation transitions. Further, 2’-O-methylation (2’-O-Me) of RNA, a common sugar modification, lowers the driving force of RNA phase transitions. These results highlight the diverse physicochemical parameters governing nucleic acid phase behavior and suggest how sugar modifications may have evolved to robustly tune the formation and dynamical arrest of RNA condensates.
TNF signaling maintains local restriction of bacterial founder populations in intestinal and systemic sites during oralYersiniainfection
Authors: Peterson Stefan T. , Dailey Katherine G. , Hullahalli Karthik , Sorobetea Daniel , Matsuda Rina , Sewell Jaydeen , Yost Winslow , O’Neill Rosemary , Bobba Suhas , Apenes Nicolai , Sherman Matthew E. , Balazs George I. , Assenmacher Charles-Antoine , Cox Arin , Lanza Matthew , Shin Sunny , Waldor Matthew K. , Brodsky Igor E.
Published: February 2025

Enteroinvasive bacterial pathogens are responsible for an enormous worldwide disease burden that critically affects the young and immunocompromised.Yersinia pseudotuberculosisis a Gram-negative enteric pathogen, closely related to the plague agentY. pestis,that colonizes intestinal tissues, induces the formation of pyogranulomas along the intestinal tract, and disseminates to systemic organs following oral infection of experimental rodents. Prior studies proposed that systemic tissues were colonized by a pool of intestinal replicating bacteria distinct from populations within Peyer’s patches and mesenteric lymph nodes. Whether bacteria within intestinal pyogranulomas serve as the source for systemic dissemination, and the relationship between bacterial populations within different tissue sites is poorly defined. Moreover, the factors that regulateYersiniacolonization and dissemination are not well understood. Here, we demonstrate, using Sequence Tag-based Analysis of Microbial Populations in R (STAMPR), that remarkably small founder populations independently colonize intestinal and systemic tissues. Notably, intestinal pyogranulomas contain clonal populations of bacteria that are restricted and do not spread to other tissues. However, populations ofYersiniaare shared among systemic organs and the blood, suggesting that systemic dissemination occurs via hematogenous spread. Finally, we demonstrate that TNF signaling is a key contributor to the bottlenecks limiting both tissue colonization and lymphatic dissemination of intestinal bacterial populations. Altogether, this study reveals previously undescribed aspects of infection dynamics of enteric bacterial pathogens.

Importance

Bacterial escape from the intestine can lead to severe disease, including sepsis, organ damage, and death. However, the intestinal bacterial population dynamics governing the colonization of mucosal and systemic tissues and the intestinal sites that seed systemic spread are not clear.Yersinia pseudotuberculosisis a rodent and human intestinal pathogen closely related to the plague agent and provides a natural rodent-adapted model to study systemic bacterial dissemination. Our findings define the infection dynamics of entericYersiniaand the impact of the innate immune system onYersiniacolonization of the intestine and systemic organs.
Freshwater snail faecal metagenomes reveal environmental reservoirs of antimicrobial resistance genes across two continents
Authors: O'Ferrall Angus M , Juhasz Alexandra , Jones Sam , Makaula Peter , Namacha Gladys , Ame Shaali , Oguttu David , Foo Aidan , Kayuni Sekeleghe A , LaCourse James E , Musaya Janelisa , Stothard Russell , Roberts Adam P
Published: February 2025

The transfer of antimicrobial resistance genes (ARGs) from environmental microbes to pathogens is a critical but underexplored One Health driver of antimicrobial resistance (AMR). Here, we evaluate freshwater snails, which are geographically widespread aquatic invertebrates, as environmental reservoirs of ARGs. We collected faeces from eight gastropod genera at 15 freshwater locations across Malawi, Uganda, Zanzibar, and the United Kingdom, and conducted the first freshwater snail faecal metagenomic sequencing study. Proteobacteria dominated the faecal microbiomes, within which Aeromonadales were strongly associated with the total ARG load. We detected putative ARGs conferring resistance to 13 distinct antibiotic classes, including carbapenem resistance genes in all countries. In Malawi, we linked blaOXA-181 (blaOXA-48-like), a putatively mobile carbapenemase gene, to Shewanella xiamenensis - the gene's known progenitor - in a metagenome-assembled genome. We detected another blaOXA-48-like variant by read-mapping from a sample in the United Kingdom and identified mobile colistin resistance (mcr)-like genes at 11 of 15 locations. Our findings highlight freshwater snail microbiomes as One Health-relevant, environmental reservoirs of clinically important ARGs.
Mapping the genetic landscape of iron metabolism uncovers the SETD2 methyltransferase as a modulator of iron flux
Authors: Martinelli Anthony W. , Wu Chun-Pei , Vornbäumen Tristan , Wit Niek , Sia Jia J. , Speak Anneliese O. , Nathan James A.
Published: February 2025

Cellular iron levels must be tightly regulated to ensure sufficient iron for essential enzymatic functions whilst avoiding the harmful generation of toxic species. Here, to better understand how iron levels are controlled, we carry out genome-wide mutagenesis screens in human cells. Alongside mapping known components of iron-sensing, we determine the relative contributions of iron uptake, iron recycling, ferritin breakdown, and mitochondrial flux in controlling the labile iron pool. We also identify SETD2, a histone methyltransferase, as a chromatin modifying enzyme that controls intracellular iron availability through ferritin breakdown. Functionally, we show that SETD2 inhibition or cancer-associated SETD2 mutations render cells iron deficient, thereby driving resistance to ferroptosis, and potentially explaining how some tumours evade anti-tumoural immunity.
Inhibitory and disinhibitory VIP IN-mediated circuits in neocortex
Authors: Dellal Shlomo , Zurita Hector , Valero Manuel , Abad-Perez Pablo , Kruglikov Ilya , Meng John , Prönneke Alvar , Hanson Jessica L. , Mir Ema , On-garo Marina , Wang Xiao-Jing , Buzsáki György , Machold Robert , Rudy Bernardo
Published: February 2025

Cortical GABAergic interneurons (INs) are comprised of distinct types that provide tailored inhibition to pyramidal cells (PCs) and other INs, thereby enabling precise control of cortical circuit activity. INs expressing the neuropeptide vasoactive-intestinal peptide (VIP) have attracted attention recently following the discovery that they predominantly function by inhibiting dendritic-targeting somatostatin (SST) expressing INs, thereby disinhibiting PCs. This VIP-SST disinhibitory circuit motif is observed throughout the neocortex from mice to humans, and serves as a key mechanism for top-down (feedback) and context-dependent information processing. Thus, VIP IN-mediated disinhibition has been found to play an important role in sensory processing, control of executive functions, attention, sensorimotor integration and other cortico-cortical and thalamocortical feedback interactions. Furthermore, VIP INs have been implicated in mediating the effects of reinforcement signals, both reward and aversive, via their responsiveness to neuromodulators such as acetylcholine (ACh), and in facilitating synaptic plasticity and learning. While it is evident from transcriptomic analyses that VIP INs are a molecularly heterogeneous group, the physiological significance of this diversity is unclear at present. Here, we have characterized the functional diversity of VIP INs in the primary somatosensory cortex by leveraging intersectional genetic approaches to study distinct VIP IN subtypes. We found that VIP INs can be divided into four different populations: a group that expresses the Ca2+-binding protein calretinin (CR), two distinct groups that express the neuropeptide cholecystokinin (CCK), and a group that does not express either CR or CCK (non-CCK non-CR; or nCCK nCR). VIP neurons in each group exhibit different laminar distributions, axonal and dendritic arbors, intrinsic electrophysiological properties, and efferent connectivity, VIP/CR INs target almost exclusively SST INs, VIP/nCCK nCR INs also mainly target SST INs but also have connections to parvalbumin (PV) expressing INs. These two groups have essentially no connectivity to pyramidal cells (PCs). On the other hand, the two types of VIP/CCK INs target PCs, but differ in the degree to which synaptic release from each type is modulated by endocannabinoids. We also found that long-range inputs differentially recruit distinct VIP IN groups. Intriguingly, we find that distinct VIP IN populations target distinct SST INs subtypes in turn, indicating the presence of specialized VIP-SST disinhibitory subcircuits. Activation of distinct VIP IN subpopulationsin vivoresults in differential effects on the cortical network, thus providing evidence for modularity in VIP IN-mediated actions during cortical information processing.
Characterizing massa intermedia morphology in schizophrenia: associations with aging, neuropsychological functioning, and atypical hippocampal development
Authors: Bergson Zachary , Roeske Maxwell J , Rogers Baxter P , Huang Anna S , Fox Victoria , Heckers Stephan , Woodward Neil D
Published: February 2025

The massa intermedia (MI) is a midline structure connecting the left and right thalamus that typically develops during the 2nd trimester of pregnancy. Missing and smaller MI has been linked to neurodevelopmental disorders, including schizophrenia (SZ), and subtle deficits in cognition. However, findings are inconsistent and the association between MI and other anatomical variants linked to atypical brain development in SZ, including incomplete hippocampal inversion (IHI), is unclear. Presence/absence and morphology of the MI were ascertained on structural T1-weighted MRI images obtained at 3T in SZ (n = 223) and healthy individuals (n = 194) and compared between groups. Associations between MI morphology, cognitive function, and incomplete hippocampal inversion (IHI) were assessed. Prevalence of missing MI was 1.7% and did not differ between groups. MI was significantly smaller in SZ (p <.001). However, follow-up analyses revealed that smaller MI size in SZ was due to a significant Diagnosis x Age interaction characterized by a stronger negative age effect in SZ. IHI was significantly more common in individuals with missing MI. Neurocognition was not correlated with MI size when controlling for age and diagnosis. Stronger effects of age on MI size in SZ suggests that abnormal MI size measured in adulthood may not be a reliable static indicator of atypical neurodevelopment, but may reflect disease progression or accelerated aging. Missing MI was rare in our sample. Conversely, missing MI is associated with IHI suggesting a shared neurodevelopmental disruption in the 2nd trimester.
Nuclear speckle proteins form intrinsic andMALAT1-dependent microphases
Authors: Shinn Min Kyung , Tomares Dylan T. , Liu Vicky , Pant Avnika , Qiu Yuanxin , Song You Jin , Ayala Yuna , Strout Gregory W. , Ruff Kiersten M. , Lew Matthew D. , Prasanth Kannanganattu V. , Pappu Rohit V.
Published: February 2025

Nuclear speckles are enriched in serine / arginine rich splicing factors (SRSFs), such as SRSF1. Splicing factors and proteins such as TDP-43 concentrate into distinct speckle territories to enable pre-mRNA processing. We have discovered that SRSFs and TDP-43 are block copolymers and the protein-specific interplay of inter-block repulsions and attractions drives spontaneous microphase separation. This gives rise to size-limited, ordered assemblies, that are 30 – 45 nm in diameter. Depending on the protein, each microphase comprises several tens to hundreds of molecules. The sub-micron scale territories observed in cells are shown to be clusters of microphases. The regulatory lncRNAMALAT1binds preferentially to SRSF1 microphases to enhance microphase separation and alter microphase structures. Microphase separation enables the concentration of finite numbers of splicing factors into assemblies with distinct nanoscale structures that can be modulated byMALAT1. Our findings provide a structural framework for the functional organization of splicing factors.
Risk-reward trade-off in motility endurance generates dichotomy in search strategies among copiotrophic marine bacteria
Authors: Keegstra Johannes M. , Landry Zachary C. , Zweifel Sophie T. , Roller Benjamin R.K. , Martínez-Pérez Clara , Clerc Estelle E. , Ackermann Martin , Stocker Roman
Published: February 2025

Coptiotrophic marine bacteria contribute significantly to carbon storage in the ocean by remineralizing organic carbon present in nutrient-rich hotspots amidst oligotrophic waters. Motility is both highly beneficial and costly in such environments, presenting copiotrophs with a risk–reward trade-off in search behavior. Here we studied the motility endurance of 26 marine isolates using video microscopy and cell tracking over two days of carbon starvation. We found that this cost-benefit trade-off results in a distinct dichotomy among marine bacteria: risk-averse copiotrophs ceased motility within hours (‘limostatic’), whereas risk-prone copiotrophs converted 10% of their biomass per day into energy to retain motility for the two days of observation (‘limokinetic’). We identified a genomic component of this dichotomy, sufficiently robust to predict the response of additional species with 83% accuracy and the prevalence of both strategies in the ocean. This dichotomy can facilitate the incorporation of the bacterial contribution in ocean carbon cycle models.