bluuebunny/crossref_metadata_2025 huggingface dataset:
Return to work after lumbar microdiskectomy – a systematic review and meta-analysis
Authors: Saltychev Mikhail , Villikka Elias , Madekivi Vilma , Pernaa Katri , Juhola Juhani
Published: January 2025

Study Design:

Systematic review and meta-analysis.

Objective:

To investigate evidence on the prevalence and timeline of RTW after lumbar microdiskectomy.

Summary of Background Data:

While lumbar microdiskectomy is a widely used and well-studied procedure, there is lack of evidence on the postoperative prevalence and schedule of return to work after this type of surgery.

Methods:

Search at Medline, Embase, Cinahl, Scopus and Web of Science. Assessment of risk of systematic bias using Quality in Prognosis Studies (QUIPS). Random effects meta-analysis and meta-regression. Adults undergoing lumbar microdiskectomy due to degenerative disc herniation, excluding spinal stenosis, percutaneous diskectomy, artificial disk, arthroplasty, laminectomy, fusion or symptoms of cauda equina.

Results:

Of identified 2,285 records, 31 were included in meta-analysis. Most of the studies had low risk of systematic bias. Pooling 21 studies, the mean prevalence of postoperative return to work was 78% (95% CI 71% to 83%). Pooling 13 studies the mean time of return to work was 4.79 (95% CI 3.88 to 5.70) weeks. The meta-regression of prevalence of return to work by the duration of follow-up resulted in significant but small coefficient of 0.02 (95% CI 0.01 to 0.03, P=0.006). There was considerable heterogeneity for all three models.

Conclusion:

The results of this review suggest that approximately 70%-80% of patients who undergo a microsurgical procedure for disc herniation return to work within the first month and a half. It also seems that returning to work after this period is quite unlikely. The duration of preoperative symptoms did not affect significantly the prevalence of RTW. Information about these trends should be taken into account both in the planning phase of the procedure and in setting goals for postoperative rehabilitation.
Long-term Postural Stability Changes After Correction of Spinal Deformity
Authors: Juncker Ryan B. , Weinberg Joshua H. , Xiao James , Ghaith Abdul Karim , Keister Alexander , Grossbach Andrew J. , Xu David S. , Viljoen Stephanus
Published: January 2025

Study Design:

Prospective cohort study.

Objective:

This study aimed to investigate the durability of postural stability after ASD correction surgery and its’ association with clinical outcomes.

Summary of Background Data:

The prevalence of symptomatic adult spinal deformity (ASD) necessitates surgical intervention, aiming to correct global spinal balance and spinopelvic parameters. Short-term studies have shown improvements in postural control following surgery, but the long-term impact remains unclear.

Methods:

This single-center prospective cohort study included adult patients undergoing long-segment fusion surgery between November 2019 and July 2021. Preoperative and postoperative balance assessments, radiographic analyses, and patient-reported outcome measures (PROMs) were conducted. Statistical analyses evaluated changes in postural stability and clinical outcomes.

Results:

Fifteen ASD patients were analyzed. Significant improvements were observed in the early postoperative period in coronal center of pressure (COP) sway (P=0.048) and amplitude (P=0.027), total COP sway (P=0.042), coronal center of gravity (COG) amplitude (P=0.013), total COG sway (P=0.044), and head sway in the coronal plane (P=0.025). These improvements were maintained at the final postoperative visit for all measurements except coronal COG amplitude (early vs. last postoperative visit, P=0.040). Radiographic parameters, including pelvic incidence – lumbar lordosis mismatch (P=0.041) and sagittal vertical axis (P=0.032), also significantly improved postoperatively. PROMs revealed significant enhancements in VAS back pain (P=0.045), RAND SF-36 pain (P=0.016), RAND SF-36 physical functioning (P=0.008), and PROMIS pain interference (P=0.032) scores at the last follow-up.

Conclusion:

These results demonstrate that the postural stability improvements seen after ASD correction are durable and correlate with enhanced clinical outcomes, such as reduced back pain and improved physical functioning. These findings underscore the clinical importance of achieving sagittal alignment in ASD patients. Further research with larger cohorts and extended follow-up periods is warranted to confirm these associations and establish postural stability assessment as a vital parameter in evaluating patients’ quality of life postoperatively.

Level of Evidence:

Level 3
Long-term outcomes of second-generation drug-eluting stents versus coronary artery bypass graft: a systematic review and meta-analysis of randomized trials and multivariable adjusted data
Authors: Carvalho Ferreira André Luiz , Benitez Gonzalez Maria Esther , Coelho Pessoa Lima Ana Emanuel , Alamino Lacalle Almir , Saad Gabriel , Guida Camila Mota
Published: January 2025

Long-term data are limited comparing percutaneous coronary intervention (PCI) with second-generation drug-eluting stents (S-DES) vs coronary artery bypass grafting (CABG) in patients with complex coronary artery disease (CAD). We aimed to conduct a systematic review and meta-analysis comparing these interventions in patients with left main or multivessel CAD. We systematically reviewed PubMed, Embase, and Cochrane for studies that compared PCI with S-DES and CABG in patients with left main or multivessel CAD with a minimum mean follow-up period of 3 years. Outcomes of interest were all-cause mortality, myocardial infarction (MI), stroke, and major adverse cardiovascular events (MACE). We extracted data from observational studies as multivariable-adjusted or propensity score-matched hazard ratio to minimize confounding and pooled hazard ratios with 95% confidence intervals (CIs) using a random effects model in Review Manager 5.4.1. We included 10 studies, 3 of which were randomized controlled trials, comprising a total of 26964 patients, of whom 14928 underwent PCI. As compared with CABG, S-DES had a significantly higher risk of all-cause mortality (hazard ratio 1.35; 95% CI 1.22–1.49; P < 0.001; I
2 = 0%), MACE (hazard ratio 1.27; 95% CI 1.08–1.50; P = 0.005; I
2 = 67%), and MI (hazard ratio 2.43; 95% CI 1.80–3.28; P < 0.01; I
2 = 0%). There was no significant difference between groups in incidence of stroke. In this meta-analysis of patients with complex CAD, PCI with S-DES was associated with an increased risk of mortality, MI, and MACE compared with CABG.
The impact of bifurcation angle on clinical outcomes in patients who underwent nano-crush technique: the insight from the multicenter EVOLUTE-CRUSH V study
Authors: Çizgici Ahmet Yaşar , Güner Ahmet , Alizade Elnur , Çetin İlyas , Serin Ebru , Doğan Abdullah , Gökçe Kaan , Serter Berkay , Çiloğlu Koray , Aktürk İbrahim Faruk , Uysal Hande , Gültekin Güner Ezgi , Akman Cemalettin , Şimşek Aybüke , Bedir Fatih Furkan , Tanik Veysel Ozan , Keskin Kudret , Püşüroğlu Hamdi , Aydin Merve , Aydin Emre , Çörekçioğlu Büşra , Köseoğlu Mehmet , Uzun Fatih
Published: January 2025

Background

This multicenter study aimed to retrospectively assess the relationship between bifurcation angle (BA) and major cardiovascular events (MACEs) in patients undergoing nano-crush technique (NCT) for complex bifurcation lesions (CBLs).

Methods

A total of 122 consecutive patients [male: 85 (69.6%), mean age: 61.53 ± 9.03 years] who underwent NCT between January 2019 and January 2024 were included. The primary endpoint was a combined endpoint (MACE) including cardiac death, target vessel myocardial infarction (TVMI), or clinically driven target lesion revascularization (TLR). Patients were classified into two groups: MACE-positive and MACE-negative patients.

Results

Among the study population, 22 patients (18%) had at least one MACE. The BA (46.89 ± 14.65° vs. 65.23 ± 10.40°, P = 0.001) was notably lower in the MACE-positive group than the MACE-negative group. In multivariable regression analysis, decreased BA was identified as one of the independent predictors of MACE (odds ratio = 0.908; 95% confidence interval: 0.852–0.969; P < 0.001). We divided the study cohort into two subgroups based on historical narrow and wide BAs (<70 vs. ≥70°). The incidence of MACE (25.3 vs. 6.4%, P = 0.008), clinically driven TLR (22.7 vs. 4.3%, P = 0.009), and TVMI (18.7 vs. 0%, P = 0.001) were notably higher in the BA <70° group than in the BA ≥70° group. Kaplan–Meier analysis also revealed that MACE-free survival was significantly lower in the BA <70° group than in the BA ≥70° group under mid-term follow-up (log-rank P = 0.009).

Conclusion

This observational multicenter study showed that the BA significantly affects mid-term outcomes in patients who underwent NCT. In addition, our findings suggest that NCT may not be a viable option in patients with narrow-angle (<70°) CBLs.
The Future of HIV: Challenges in meeting the 2030 Ending the HIV Epidemic in the U.S. (EHE) reduction goal
Authors: Bleichrodt Amanda M. , Okano Justin T. , Fung Isaac Ch. , Chowell Gerardo , Blower Sally
Published: January 2025

Objective(s):

To predict the burden of HIV in the United States (US) nationally and by region, transmission type, and race/ethnicity through 2030.

Methods:

Using publicly available data from the CDC NCHHSTP AtlasPlus dashboard, we generated 11-year prospective forecasts of incident HIV diagnoses nationally and by region (South, non-South), race/ethnicity (White, Hispanic/Latino, Black/African American), and transmission type (Injection-Drug Use, Male-to-Male Sexual Contact (MMSC), and Heterosexual Contact (HSC)). We employed weighted (W) and unweighted (UW) n-sub-epidemic ensemble models, calibrated using 12 years of historical data (2008–2019), and forecasted trends for 2020–2030. We compared results to identify persistent, concerning trends across models.

Results:

We projected substantial decreases in incident HIV diagnoses nationally (W: 27.9%, UW: 21.9%), and in the South (W:18.0%, UW: 9.2%) and non-South (W: 21.2%, UW: 19.5%) from 2019 to 2030. However, concerning nondecreasing trends were observed nationally in key sub-populations during this period: Hispanic/Latino persons (W: 1.4%, UW: 2.6%), Hispanic/Latino MMSC (W: 9.0%, UW: 9.9%), people who inject drugs (PWID) (W: 25.6%, UW: 9.2%), and White PWID (W: 3.5%, UW: 44.9%). The rising trends among Hispanic/Latino MMSC and overall PWID were consistent across the South and non-South regions.

Conclusions:

Although the forecasted national-level decrease in the number of incident HIV diagnoses is encouraging, the US is unlikely to achieve the Ending the HIV Epidemic in the US goal of a 90% reduction in HIV incidence by 2030. Additionally, the observed increases among specific subpopulations highlight the importance of a targeted and equitable approach to effectively combat HIV in the US.
Normothermic Liver Machine Perfusion At a Large European Center –Real World Outcomes Following 238 Applications
Authors: Krendl Felix J. , Cardini Benno , Fodor Margot , Singh Jessica , Ponholzer Florian , Messner Franka , Weissenbacher Annemarie , Resch Thomas , Maglione Manuel , Margreiter Christian , Eschertzhuber Stephan , Irsara Christian , Griesmacher Andrea , Schennach Harald , Breitkopf Robert , Schlosser Lisa , Zoller Heinz , Tilg Herbert , Oberhuber Rupert , Schneeberger Stefan
Published: January 2025

Objective:

To report outcomes from routine clinical practice of liver transplantation (LT) following normothermic liver machine perfusion (NLMP) and compare to LT after static cold storage (SCS).

Background:

NLMP is emerging as a clinical routine in LT as has recently received renewed attention, however outcomes outside of clinical trials are lacking.

Methods:

All adult LT between February 2018 and January 2023 were included. Comprehensive viability assessment was applied during NLMP. Outcomes were compared between NLMP and SCS recipients, as well as benchmark and non-benchmark cases.

Results:

Of the 332 LT included, 174 underwent NLMP and 158 were transplanted following SCS. Sixty-seven organs were accepted and transplanted only under the premise of NLMP. One-year graft survival for SCS and NLMP recipients was 83.8% vs. 81.3% and 93.4% for benchmark cases in the overall cohort. Total preservation time had no influence on graft survival in the NLMP group but was associated with inferior 1-year graft survival in the SCS group. NLMP usage increased significantly over the duration of the study period, as did the median total preservation time. With increasing NLMP use and longer preservation times, nighttime surgery decreased significantly from 41.9% to 4.2%.

Conclusions:

Prolonged preservation times ease logistics and enable daytime surgery. The possibility of NLMP offers to expand liver transplantation without negatively affecting outcomes.
Feasibility and Acceptability of a Virtual “Dementia Awareness for Caregivers” Course in Brazil and India
Authors: de Carvalho Raquel Luiza Santos , Fisher Emily , Natarajan Nirupama , Hui Esther K. , Venkatesan Shreenila , Vaitheswaran Sridhar , Laksminarayanan Monisha , Brum Paula Schimidt , Naylor-Batista Renata , Bertrand Elodie , Mograbi Daniel C. , Ferri Cleusa P. , Stoner Charlotte , Spector Aimee
Published: January 2025

Objective:

To establish whether a virtual dementia awareness course is feasible for caregivers of people with dementia in Brazil and India.

Methods:

A pre/posttest single group, multisite feasibility study, mixed methods exploratory design was applied. Primary caregivers of people with dementia in Brazil and India took a 3 to 4-hour course adapted for online delivery, with 10 to 15 caregivers. Measurements encompassed self-reports of carer competence, attitudes to dementia, and caregiver burden; satisfaction questionnaire completed immediately after the intervention; open-ended questions at 1-month follow-up to assess if caregivers applied information to caregiving role; semistructured interviews about how the intervention changed caregivers’ behavior and attitudes towards dementia.

Results:

Of the 70 caregivers who received the intervention (Brazil = 34; India = 36), 54 (77.1%) completed postintervention outcomes, and 39 (55.7%) completed questionnaires at 1-month follow-up assessment. Significant improvements were observed in attitudes to dementia in both countries and self-perceived carer competence (in India) postintervention. The themes from the 9 semistructured interviews were: acceptability, feasibility, change of behavior/attitude, and suggestions for future sessions.

Conclusions:

Dementia awareness course was a feasible online intervention to improve dementia awareness among family caregivers across countries. It offers a standardized yet flexible methodology, with promising outcomes that need to be evaluated in a full randomized controlled trial.
A hydrocele revealing epididymal tuberculosis
Authors: Ben Lahlou Yassine , Laanibi Zakaria , Malihy Zakaria , Benaissa Elmostapha , Maleb Adil , Elktaibi Abderrahim , Chadli Mariama , Elouennass Mostapha
Published: January 2025

Abstract:

Genitourinary tuberculosis is a severe form of extrapulmonary tuberculosis. The kidneys are the most commonly affected organs, followed by the epididymis, testicles, bladder, ureter, and prostate. Notably, epididymal tuberculosis is one of the forms of genital tuberculosis presenting with specific clinical features, which may include epididymitis, orchid-epididymitis, or hydrocele.
We report the case of a patient with a hydrocele that revealed epididymal tuberculosis. Utilizing molecular biology techniques, a diagnostic of epididymal tuberculosis was established. The patient was treated conservatively with tuberculosis medication for six months.
DETECTION AND ANTIBIOTIC RESISTANCE OF SALMONELLA ISOLATES FROM SELECTED POULTRY FARMS IN DAR ES SALAAM, TANZANIA.
Authors: Mwambene Saxon Joseph , Mtenga Adelard B. , Chengula Augustino A. , Hoza Abubakar S.
Published: January 2025

Introduction

Salmonella, one of the most frequent foodborne bacteria, is linked to 155,000 annual mortality and 93.8 million foodborne illnesses. Rampant use of antibiotic agents to combat Salmonellosis in poultry has contributed to the emergence of resistance against commonly used antibiotics.

Methodology

A cross-section study was conducted between January and June 2023. Purposive sampling was used to select farms, poultry faecal droppings were collected to determine the occurrence of multidrug-resistant (MDR) Salmonella spp. Samples were examined for the presence of Salmonella by standard microbiological techniques. Conventional biochemical tests and molecular methods such as PCR and partial DNA sequencing were used for the identification of Salmonella isolates. Antimicrobial susceptibility testing was performed to identify Salmonella isolates resistant to seven commonly used classes of antibiotics.

Results

The overall Salmonella spp isolated from faecal droppings from the selected farms was 6.04% (n=48). Of the PCR-confirmed isolates, 64.3% (n=18) were resistant to more than two classes of antibiotics and hence considered MDR. The highest resistance was observed with ampicillin (92.9%), followed by tetracycline (69%), ciprofloxacin (42.9%), sulfonamide (42.9%), gentamicin (35.7%), and azithromycin (28.9%). All the isolates were susceptible to chloramphenicol (100%). Twenty-eight (28) isolates were sequenced and only sixteen (16) sequences met the criteria for phylogenetic analysis. All the sixteen (16) Sequences clustered together with Salmonella enterica sub spp. enterica with accession number EU348369 which was isolated from chickens, pigs, and foods.

Conclusion

The observed high level of antibiotic resistance found in this study could be attributed to the unwarranted use of antibiotics. To limit the use of antibiotics in poultry farming at the farm level, immediate action is needed including advocating for prudent use of antibiotics in poultry production systems by strengthening extension services to poultry farmers and use of farm biosecurity.
Reg-GPT™: A Conversational AI Model for Enhanced Decision-Making in Regenerative Medicine
Authors: Maharaj Dipnarine , Zhang Wen
Published: January 2025

Background

As artificial intelligence (AI) continues to transform various aspects of our lives, conversational AI models have become increasingly sophisticated. The development of more accurate and informative language processing assistants has significant implications for numerous fields, including health care, medical service, and research assistance.

Materials and Methods

Reg-GPT™ was developed by the Maharaj Institute of Immune Regenerative Medicine (MIIRM) using a combination of supervised and unsupervised learning techniques. The LLaMa 3.1 model’s parameters were fine-tuned using vast amounts of text data, enabling Reg-GPT™ to learn from its interactions with users.

Results

Our evaluation shows that Reg-GPT™ model performs well in several key areas, including response accuracy, fluency, and engagement. The results highlight the potential benefits of integrating Reg-GPT™ into regenerative medicine (RM) applications.

Conclusion

This article provides a comprehensive introduction to Reg-GPT™, showcasing its capabilities, performance, and potential uses. We believe that Reg-GPT™ has the potential to provide significant value in the RM and Medicare fields.
Heartfelt gaze: Cardiac afferent signals and vagal tone affect gaze perception
Authors: Lin Yaojie , Isomura Tomoko
Published: January 2025

Perceiving others’ gaze direction is an essential aspect of social interactions. The cone of direct gaze (CoDG) refers to the range within which an observer perceives gaze as looking directly at them. Previous research has demonstrated that self-relevant exteroceptive cues can widen CoDG. However, the effect of self-relevant interoceptive information on the CoDG remains unknown. In the present study, we used a modified gaze discrimination task to synchronize face stimuli with various gaze directions to specific phases of the cardiac cycle. The results showed that participants with higher heart rate variability (HRV) exhibited a wider CoDG during cardiac systole (when cardiac signals are maximally represented in the brain), but not during cardiac diastole (when these signals are quiescent). Moreover, this effect was independent of individual differences in anxiety levels and autistic traits. We interpret these findings as evidence that individuals with greater cardiac vagal control are more sensitive to cardiac afferent signals during systole, which in turn leads to a stronger self-directed perception of others’ gaze under transient and ambiguous gaze perception conditions. Our findings highlight the self-referential role of cardiac interoceptive signals in gaze perception, expanding our knowledge of interoceptive influences on social judgment.
Systematic assessment of microenvironment-dependent transcriptional patterns and intercellular communication
Authors: Pareja-Lorente Elena , Aloy Patrick
Published: January 2025

Understanding cell-cell communication and its dependence on spatial organization is critical for unraveling tissue complexity and organ function. This study integrates single-cell RNA sequencing (scRNA-seq) with spatial transcriptomics (ST) to systematically assess how spatial niches influence gene expression and intercellular communication. Using breast cancer, brain cortex, and heart datasets, our analyses reveal limited global transcriptional changes in cells depending on their spatial microenvironment, with differential gene expression observed in less than half the samples explored. Moreover, cell-cell communication predictions, derived from ligand-receptor pairs, exhibit minimal correlation with spatial colocalization of cell types. Overall, our study underscores the limitations of using scRNA-seq data to capture niche-specific molecular interactions, even when spatial information is leveraged, and it highlights the need for novel strategies to refine our understanding of intercellular communication dynamics at molecular level.
Comparison of embolic effects between permanent and novel resorbable microspheres in a porcine renal artery embolization model for TAE
Authors: Agarwal Sankalp , Pandey Masum , Duggan Ronan , Brien Con O’ , Lewis Andrew. L. , Duffy Brendan , McCabe Joan , Farrissey Liam
Published: January 2025

Embolotherapy has been widely practised for musculoskeletal (MSK) pain relief applications. It involves the intentional occlusion of blood vessels to reduce or prevent blood flow to target regions or organs using a vascular embolic agent. This study evaluated renal artery embolization using resorbable microspheres (SakuraBead, RM) compared to permanent microspheres (Embozene, PM) in Yorkshire swine, assessing vessel occlusion duration, local and systemic reactions, and potential adverse effects. Angiography was performed to confirm successful stasis at all injection sites. Clinical observations, body weights, and pathology were monitored at regular intervals, and animals were euthanized at 24 hours, and on Days 3, 7, and 28 for necropsy and histomorphometric analysis. Results showed that all animals survived without significant adverse effects, maintaining body weight and condition. No significant hematologic or serum chemistry abnormalities were observed, except for transiently elevated activated partial thromboplastin time in five animals’ post-treatment. Macroscopically, treatment-related findings were minimal in the RM group and more pronounced in the PM group. Histologically, RM was rarely observed beyond 24 hours, with negligible inflammation and vascular injury. In contrast, PM persisted, accompanied by mild inflammation and vascular injury extending to the tunica media or adventitia. No systemic tissue responses were detected in either group. This study demonstrated that RM provides effective, transient embolization with minimal local or systemic adverse effects, making it suitable for indications such as genicular artery embolization, tendinopathy, and adhesive capsulitis, where temporary vessel occlusion is required.
On the biodegradation of micropatterned polymeric films
Authors: Guerriero Irene , Pesce Cristiano , Spanò Raffaele , Sganga Stefania , Tirelli Nicola , Di Mascolo Daniele , Palange Anna Lisa , Decuzzi Paolo
Published: January 2025

Abstract

Polymeric implants for local drug delivery offer significant advantages for treating various medical conditions by enabling the temporal and spatial control of drug release, improving efficacy, and reducing systemic side effects. In this context, µMESH, a 20 μm thin, dual-compartmentalized film comprising a poly(lactic-co-glycolic acid) (PLGA) micronetwork intercalated with a polyvinyl alcohol (PVA) microlayer, represents an interesting opportunity as its geometry can be systematically and accurately micropatterned during the fabrication process, enabling the systematic analysis of the effect of geometry on biodegradation rates mechanisms. In this study, four different µMESH films were realized with different surface area-to-volume ratios (Sa/V), ranging from 0.67 to 1.7 µm−1. After characterizing the µMESH geometry via fluorescent and scanning electron microscopy, biodegradations studies were performed up to 60 days in different media to assess the mass loss of PLGA, the reduction in PLGA molecular weight, and the formation of macroscopic defects – pores, holes and crack – within the PLGA micronetwork. By comparing the four µMESH films among themselves and to a flat, continuous PLGA slab (FLAT), it was confirmed the importance of the surface-to-volume ratio and demonstrated that µMESH with higherSa/Vratios exhibited slower degradation rates compared to FLAT. Scanning electron microscopy images of the PLGA micronetworks revealed morphological changes indicative of bulk erosion, including surface roughening and pore formation, in FLAT and µMESH configurations with lowSa/Vratios. These findings confirm that film micropatterning significantly influences degradation kinetics.
Blood-borne sphingosine 1-phosphate maintains vascular resistance and cardiac function
Authors: Gaudio Ilaria Del , Bonnin Philippe , Roy-Vessiers Emilie , Robidel Estelle , Garcia Manuella , Proux Coralyne , Boutigny Alexandre , Baudrie Veronique , Ha Hoa TT , Couty Ludovic , Faedda Nicolo , Mebrek Nesrine , Morel Théo , Nitzsche Anja , Baron Stéphanie , Lenoir Olivia , Tharaux Pierre-Louis , Zennaro Maria-Christina , Nguyen Long N. , Henrion Daniel , Camerer Eric
Published: January 2025

G protein-coupled receptors (GPCRs) are key regulators of cardiovascular function that provide targets for the treatment of cardiovascular disease. Sphingosine 1-phosphate (S1P) is an erythrocyte- and platelet-derived lipid mediator with cognate GPCRs on endothelial cells (EC), vascular smooth muscle cells (VSMC) and cardiomyocytes. S1P circulates in plasma bound to apolipoprotein M (ApoM)-containing high-density lipoproteins (HDL) and to albumin. Circulating S1P levels correlate positively with systolic blood pressure in hypertension and negatively with severity in septic shock and with left ventricular (LV) function in coronary heart disease. In mice, impaired S1P binding to HDL or signaling to EC both trigger hypertension, supporting an essential role for HDL-S1P in supporting endothelial function. The roles of albumin-S1P and myocyte S1PRs in cardiovascular homeostasis remain incompletely defined.

Contrasting isolated HDL-S1P deficiency, we report that non-selective depletion of circulating S1P pools in mice impairs LV contractile function and induces hypotension and resistance to the spontaneous increase in blood pressure with age. Cardiac output was preserved in naïve S1P deficient mice by compensatory LV dilation, but cardiac reserve reduced in a dobutamine stress test. These phenotypes tracked with hematopoietic cell S1P production and were partially or fully reversed by erythrocyte transfusion. Hypotension was accompanied by reduced peripheral resistance, and S1P infusion dose-dependently increased vascular resistance in isolated perfused kidneys from wild-type mice but not mice with compound deficiency in S1PR2&3. Epistatic analysis supported a critical role for S1PR3 in S1P-dependent blood pressure regulation and pointed to a distinct origin of the cardiac phenotype. Although circulating S1P is elevated in hypertensive mice and humans, increasing circulating S1P was not sufficient to induce hypertension in naive mice.

These observations suggests that albumin-S1P crosses the endothelium in resistance arteries to gain access to contractile VSMC S1P receptors, and that myocyte S1PR signaling is essential for vascular resistance and blood pressure maintenance in mice. They also highlight the role for plasma chaperones in specifying vascular responses to S1P and the relevance of S1P as a biomarker and potential therapeutic target for blood pressure regulation and heart failure.
Investigating the genomic landscape of mouse models of breast cancer metastasis
Authors: Ross Christina R. , Szczepanek Karol , Sanford Jack , Qiu Tinghu , Pearce Larry , Hunter Kent W.
Published: January 2025

Metastasis remains a major cause of cancer mortality. AbstractThis study, expanding upon previous findings in the MMTV-PyMT model, investigated four independent mouse models, representing luminal (MMTV-PyMT, MMTV-Myc), HER2-amplified (MMTV-Her2) and triple negative (C3(1)TAg) breast cancer subtypes. Consistent with previous results, limited evidence for metastasis-associated somatic point mutations was found for all models. We also found that oncogenic drivers significantly influenced the number and size of metastasis-specific copy number variations (MSCNVs), but common driver-independent MSCNVs were rare. Furthermore, analyzing a cohort with varying genetic backgrounds while maintaining a constant oncogenic driver (PyMT) revealed that genetic background profoundly impacts MSCNVs. Transcriptome analysis demonstrated that oncogenic drivers strongly shaped metastasis-specific gene expression (MSGE), with each driver exhibiting distinct expression profiles. In contrast, MSGE in the PyMT-F1 cohort was more variable across strains. Despite the diversity of MSCNV and MSGE, functional analysis revealed that both mechanisms converge on the modulation of key cellular processes, including immune responses, metabolism, and extracellular matrix interactions. These findings emphasize the complex interplay between oncogenic drivers and genetic background in shaping the genomic and transcriptional landscapes of metastatic lesions.
High fat high sucrose exposure during lactation but not during the post-weaning period programs impaired glucose homeostasis
Authors: Goergen Anne , Borsigova Marcela , Wueest Stephan , Konrad Daniel
Published: January 2025

Nutrition during critical developmental windows plays a pivotal role in shaping long-term metabolic health. Exposure to a Western diet in early life may lead to altered metabolic programing, potentially influencing the risk to develop obesity and type 2 diabetes. In particular, an early exposure to an obesogenic diet may induce a metabolic program that only emerges upon dietary challenges later in life. Accordingly, understanding the long-term impact of nutritional insults in different stages of early life may provide strategies for primary prevention. Therefore, the present study aimed to determine which time window in the post-natal period is most critical for long-term metabolic health. To this end, pups born to lean mouse dams were exposed to a high-fat, high-sucrose (HFHS) diet for 3 weeks during lactation or in the post-weaning period. Thereafter, mice were either fed a regular chow diet until the age of 30 weeks or exposed to a second bout of HFHS diet for the last 12 weeks. Metabolic health and development of obesity was assessed by regular monitoring of glucose homeostasis and body weight gain. 12 week-old mice with lactational exposure to a HFHS diet revealed a significantly impaired glucose tolerance compared to control mice, while glucose tolerance of post -weaning exposed mice was similar to the control group. Moreover, a second bout of HFHS diet impaired glucose tolerance and increased body and adipose tissue weight in mice with lactational exposure to a significant greater extent than in post-weaning exposed mice. Hence, exposure to HFHS during lactation but not during the post-weaning period programs impaired glucose homeostasis, suggesting that the lactational window may be more critical in terms of metabolic programing.
Combining SMN2 splicing modifiers with HDAC6 inhibition greatly improves muscle function and survival in Spinal Muscular Atrophy
Authors: Osseni Alexis , Slika Rasha , Coudert Laurent , Conjard-Duplany Agnes , Weill Laure , Belotti Edwige , Clerc Zoe , Gangloff Yann gael , Sapaly Delphine , Vuillerot Carole , Leblanc Pascal , Charbonnier Frederic , Schaeffer Laurent
Published: January 2025

Spinal muscular atrophy (SMA) is a rare, progressive and severe neuromuscular disease. It is mostly caused by mutations in the SMN gene, which lead to the death of spinal cord motor neurons. In the absence of treatment, more than half of affected children die before the age of two. Recently, groundbreaking gene therapies were developed, allowing children to survive. However, a new clinical presentation of the disease has emerged in treated patients, characterized by ongoing functional deficits and a disability mainly due to persistent muscle atrophy. Over the last years, treatments of various animal models of neuromuscular disorders have shown the ability of inhibitors of the non-conventional histone deacetylase 6 (HDAC6) to reduce inflammation, fibrosis and muscle atrophy, and to ameliorate acetylcholine receptor distribution at the neuromuscular junction, microtubule network and mitochondrial transport in axons, indicating potential interest for the treatment of neuromuscular disorders. The present study was designed to properly characterize the effect of HDAC6 inhibition on muscle cells proliferation and differentiation and to evaluate in vivo if HDAC6 inhibition combined with the new standard of care treatments of SMA could ameliorate skeletal muscle and general status of a SMA mouse model. Here, we report that HDAC6 and tubulin acetylation controls myotube formation and maturation in vitro. In particular, HDAC6 inhibition increases the size of SMA patients-derived muscle primary myotubes. In vivo, when combined with ASOs inducing exon 7 inclusion in SMN2 RNA in motoneurons, HDAC6 systemic inhibition strongly improved muscle strength, mass, function, and longevity of the Smn[Delta]7/[Delta]7; hSMN2+/- mouse model of SMA. These findings provide evidence that in muscle cells, HDAC6 is the only tubulin deacetylase and that selective inhibition of HDAC6 improves myogenic progression and that HDAC6 inhibitors are good candidates to ameliorate persisting symptoms of SMA patients treated with the new standard of care.
CARDBiomedBench: A Benchmark for Evaluating Large Language Model Performance in Biomedical Research
Authors: Bianchi Owen , Willey Maya , Alvarado Chelsea X. , Danek Benjamin , Khani Marzieh , Kuznetsov Nicole , Dadu Anant , Shah Syed , Koretsky Mathew J. , Makarious Mary B. , Weller Cory , Levine Kristin S. , Kim Sungwon , Jarreau Paige , Vitale Dan , Marsan Elise , Iwaki Hirotaka , Leonard Hampton , Bandres-Ciga Sara , Singleton Andrew B , Nalls Mike A , Mokhtari Shekoufeh , Khashabi Daniel , Faghri Faraz
Published: January 2025

Backgrounds

Biomedical research requires sophisticated understanding and reasoning across multiple specializations. While large language models (LLMs) show promise in scientific applications, their capability to safely and accurately support complex biomedical research remains uncertain.

Methods

We presentCARDBiomedBench, a novel question-and-answer benchmark for evaluating LLMs in biomedical research. For our pilot implementation, we focus on neurodegenerative diseases (NDDs), a domain requiring integration of genetic, molecular, and clinical knowledge. The benchmark combines expert-annotated question-answer (Q/A) pairs with semi-automated data augmentation, drawing from authoritative public resources including drug development data, genome-wide association studies (GWAS), and Summary-data based Mendelian Randomization (SMR) analyses. We evaluated seven private and open-source LLMs across ten biological categories and nine reasoning skills, using novel metrics to assess both response quality and safety.

Results

Our benchmark comprises over 68,000 Q/A pairs, enabling robust evaluation of LLM performance. Current state-of-the-art models show significant limitations: models like Claude-3.5-Sonnet demonstrates excessive caution (Response Quality Rate: 25% [95% CI: 25% ± 1], Safety Rate: 76% ± 1), while others like ChatGPT-4o exhibits both poor accuracy and unsafe behavior (Response Quality Rate: 37% ± 1, Safety Rate: 31% ± 1). These findings reveal fundamental gaps in LLMs’ ability to handle complex biomedical information.

Conclusion

CARDBiomedBench establishes a rigorous standard for assessing LLM capabilities in biomedical research. Our pilot evaluation in the NDD domain reveals critical limitations in current models’ ability to safely and accurately process complex scientific information. Future iterations will expand to other biomedical domains, supporting the development of more reliable AI systems for accelerating scientific discovery.
Branched chain fatty acid-rich diet promotes lipid droplet enlargement and impacts organismal health in Caenorhabditis elegans
Authors: Li Kam Ue Roy , Lo Wing Ka , Yang Meigui , Wang Chenyin , Yin Lau Chun , Lee Jetty Chung-Yung , Zheng Chaogu
Published: January 2025

Considerable amounts of branched chain fatty acids (BCFAs) are present in the human diet from beef and dairy products. BCFAs can also be produced by the human gut microbiota and synthesized from branched chain amino acids. However, the physiological impact of a BCFA-rich diet on lipid metabolism and organismal health is unclear. In this study, by screening a collection of dietary bacteria, we find that the BCFA-rich Microbacterium diet causes the formation of supersized LDs and delays development, reduces brood size, and shortens lifespan of C. elegans. The high-BCFA diet downregulates argk-1/creatine kinase to inhibit the AMPK pathway and beta-oxidation and upregulates fat-7/desaturase to promote the accumulation of PUFA, which enhances lipogenesis and LD expansion. We also isolate a gain-of-function mutation in scav-4/CD36, which enhances BCFA absorption and exacerbates BCFA-induced LD enlargement, demonstrating that host genetic variation in a fatty acid transporter could influence the susceptibility to a high-BCFA diet.
Predictive Coding algorithms induce brain-like responses in Artificial Neural Networks
Authors: Gütlin Dirk , Auksztulewicz Ryszard
Published: January 2025

This study explores whether predictive coding (PC) inspired Deep Neural Networks can serve as biologically plausible neural network models of the brain. We compared two PC-inspired training objectives, a predictive and a contrastive approach, to a supervised baseline in a simple Recurrent Neural Network (RNN) architecture. We evaluated the models on key signatures of PC, including mismatch responses, formation of priors, and learning of semantic information. Our results show that the PC-inspired models, especially a locally trained predictive model, exhibited these PC-like behaviors better than a Supervised or an Untrained RNN. Further, we found that activity regularization evokes mismatch response-like effects across all models, suggesting it may serve as a proxy for the energy-saving principles of PC. Finally, we find that Gain Control (an important mechanism in the PC framework) can be implemented using weight regularization. Overall, our findings indicate that PC-inspired models are able to capture important computational principles of predictive processing in the brain, and can serve as a promising foundation for building biologically plausible artificial neural networks. This work contributes to our understanding of the relationship between artificial and biological neural networks, and highlights the potential of PC-inspired algorithms for advancing brain modelling as well as brain-inspired machine learning.
NAc-DBS selectively enhances memory updating without effect on retrieval
Authors: Pérez-Segura Andrés , Medina Jorge , Cerdán Cerdá Antonio , Sánchez-Ferri Cristina , Torres Daniel , Mirasso Claudio R. , Strange Bryan , Eguíluz Víctor M. , Lacasa Lucas , Canals Santiago
Published: January 2025

Deep brain stimulation (DBS) has emerged as a widely used therapeutic option when pharmacological treatments prove ineffective or refractory for psychiatric patients. The nucleus accumbens (NAc) represents a frequently targeted site in DBS interventions due to its demonstrated safety profile and therapeutic efficacy in obsessive-compulsive disorder, major depression, and anorexia nervosa. However, limited mechanistic understanding hampers its broader clinical applicability. This study sought to delineate the distinct behavioural dimensions modulated by NAc-DBS, its impact on distinct facets of memory, and to elucidate the underlying brain-network mechanism of action. We developed a novel spatial navigation task for rats and employed a high-dimensional behavioural analysis complemented by fMRI to dissect the cognitive, behavioural and neurobiological effects of NAc-DBS. Active NAc-DBS produced a selective enhancement of long-term memory encoding without affecting memory recall or working memory. We found no effect of NAc-DBS on motor, appetitive or stress-related behaviours. Sustained neuronal activation in the NAc, septum, entorhinal and insular cortex demonstrated no desensitization to chronic NAc-DBS, which triggered a functional reorganization among dopaminergic-related structures. These findings suggest that NAc-DBS induces a functional reorganization in the mesocorticolimbic system, potentially mimicking a dopaminergic novelty signal to enhance memory updating. This provides a mechanistic basis for the therapeutic use of NAc-DBS, particularly in improving cognitive flexibility in psychiatric disorders.
Reciprocal interaction between cortical SST and PV interneurons in top-down regulation of retinothalamic refinement
Authors: Jiang Qiufen , Wu Sherry Jingjing , Fishell Gord , Chen Chinfei
Published: January 2025

Refinement of thalamic circuits is crucial for the proper maturation of sensory circuits. In the visual system, this process is regulated by corticothalamic feedback during the experience-dependent phase of development. Yet the cortical circuits modulating this feedback remain elusive. Here, we demonstrate opposing roles for cortical somatostatin (SST) and parvalbumin (PV) interneurons in shaping retinogeniculate connectivity during the thalamic sensitive period (P20-30). Early in the refinement process, SST interneurons promote the strengthening and pruning of retinal inputs in the thalamus, as evidenced by disrupted synaptic refinement following their ablation. In contrast, PV interneurons, which mature later, act as a brake on this refinement, with their ablation leading to enhanced pruning of retinogeniculate connections. Notably, manipulating the relative balance between these inhibitory circuits can regulate sensory deprivation-induced retinogeniculate remodeling. Taken together, our findings show that cortical SST and PV interneuron circuits drive reciprocal antagonism that gate experience-dependent feedforward thalamic refinement.
Covariation of amino acid substitutions in the HIV-1 envelope glycoprotein gp120 and the antisense protein ASP associated with coreceptor usage
Authors: Pavesi Angelo , Romerio Fabio
Published: January 2025

The tropism of the Human Immunodeficiency Virus type 1 (HIV-1) is determined by the use of either or both of the chemokine coreceptors CCR5 (R5) or CXCR4 (X4) for entry into the target cell. The ability of HIV-1 to bind R5 or X4 is determined primarily by the third variable loop (V3) of the viral envelope glycoprotein gp120. HIV-1 strains of pandemic group M contain an antisense gene termedasp, which overlapsenvoutside the region encoding the V3 loop. We previously showed that the ASP protein localizes on the envelope of infectious HIV-1 virions, suggesting that it may play a role in viral entry. In this study, we first developed a statistical method to predict coreceptor tropism based on the Fisher’s linear discriminant analysis. We obtained three linear discriminant functions able to predict coreceptor tropism with high accuracy (94.4%) when applied to a training dataset of V3 sequences of known tropism. Using these functions, we predicted the tropism in a dataset of HIV-1 strains containing a full-lengthaspgene. In the amino acid sequence of ASP proteins expressed from theseaspgenes we identified five positions with substitutions significantly associated with viral tropism. Interestingly, we found that these substitutions correlate significantly with substitutions at six amino acid positions of the V3 loop domain associated with tropism. Altogether, our computational analyses identify ASP amino acid signatures coevolving with V3 and potentially affecting HIV-1 tropism, which can be validated throughin vitroandin vivoexperiments.
The Innexin 7 gap junction protein contributes to synchronized activity in theDrosophilaantennal lobe and regulates olfactory function
Authors: Fuenzalida-Uribe Nicolás , Hidalgo Sergio , Silva Bryon , Gandhi Saurin , Vo David , Zamani Parham , Holmes Todd C. , Sayin Sercan , Grunwald-Kadow Ilona , Hadjieconomou Dafni , O’Dowd Diane K. , Campusano Jorge M.
Published: January 2025

In the mammalian olfactory bulb (OB), gap junctions coordinate synchronous activity among mitral and tufted cells to process olfactory information. In insects, gap junctions are also present in the Antennal Lobe (AL), a structure homologous to the mammalian OB. The invertebrate gap junction protein ShakB contributes to electrical synapses between AL Projections Neurons (PNs) inDrosophila. Other gap junction proteins, including Innexin 7 (Inx7), are also expressed in theDrosophilaAL, but little is known about their contribution to intercellular communication during olfactory information processing. Here we report spontaneous calcium transients in PNs grown in cell culture that are highly synchronous when these neurons are physically connected. RNAi-mediated knock down of Inx7 in cultured PNs blocks calcium transient neuronal synchronization.In vivo, downregulation of Inx7 in the AL impairs both vinegar-induced electrophysiological calcium responses and behavioral responses to this appetitive stimulus. These results demonstrate that Inx7-encoded gap junctions functionally coordinate PN activity and modulate olfactory information processing in the adultDrosophilaAL.
A Screening Approach Unveils an Unknown Mn2+-dependent Endopolyphosphatase Activity in Yeast
Authors: Moser Sandra , Hans Gloria , Saiardi Adolfo , Bru Samuel , Taskin Asli A. , Meisinger Chris , Jessen Henning J.
Published: January 2025

Inorganic polyphosphate (polyP) is a ubiquitous biopolymer composed of multiple orthophosphates connected by energy-rich phosphoanhydride bonds. In organisms, polyP is digested by two types of enzymes: exopolyphosphatases, which shorten the chain from the ends by cleaving off monophosphate units, and endopolyphosphatases, which cut the chain internally. While several continuous methods are available to monitor exopolyphosphatase activity, endopolyphosphatase activity assays are less common and typically involve multiple tedious steps. Here, we introduce FRET-polyP8, a novel probe for real-time detection of endopolyphosphatase activity. The FRET assay enabled rapid, highly sensitive, single-step detection of specific endopolyphosphatase activity both from isolated proteins and cell extracts. The simple read-out additionally enabled enzyme inhibitor screening. Furthermore, a novel Mn2+-dependent endopolyphosphatase activity in baker’s yeast was detected in a quadruple mutant, highlighting the ability to screen for metal-dependence of new endopolyphosphatase activity. This approach thus represents a significant addition to existing methodologies, facilitating the discovery and classification of new endopoly-phosphatases and their inhibitors to advance our understanding of polyP metabolism and regulation.