bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparison of frailty screening tools in predicting length of stay and disability in older patients on internal medicine inpatient wards transferred from the emergency department: A retrospective observational study
Authors: Kayhan Kocak Fatma Ozge , Şama Musa Gürsu , Fehimoğlu Hüseyin Caner , Emekdaş Bariş , Akyol Murat
Published: February 2025

The aim of this study is to compare frailty screening tools in predicting length of stay (LOS) in older patients on internal medicine inpatient wards transferred from the emergency department (ED). This cross-sectional retrospective study involving 186 subjects aged 65 years or older was conducted at tertiary hospital internal medicine inpatient wards transferred from the ED from September to November 2023. Frailty was defined by the Clinical Frailty Scale (CFS), the identification of Seniors At Risk Tool and the Triage Risk-Screening Tool (TRST). Dependency was defined by Katz Index of Independence in activities of daily living (ADL) and the Lawton instrumental ADL. The presence of frailty according to the CSF and TRST was associated with a long LOS (coefficient of regression β = 0.2 with P < .05). But, in binary logistic regression analysis, there was no association between long LOS and frailty scales. All frailty tools were statistically significant predictors for disability (P < .001). Our findings suggest that, among the tools evaluated, the CFS may be the most robust predictor of both LOS and functional dependency, although its predictive power for actual disability remains limited. Future studies should focus on refining these tools for greater accuracy in predicting functional outcomes and should examine how factors such as polypharmacy and comorbidities impact frailty and hospital outcomes. Additionally, longitudinal studies are needed to establish causative relationships between frailty, LOS, and functional decline.
Diagnosis of piriformis syndrome based on the piriformis muscle cross-sectional area on hip MRI
Authors: Lim Chaewan , Park Hyung-Bok , Kim Young Uk
Published: February 2025

Piriformis syndrome (PS) is a condition in which the piriformis muscle characterized by buttock and hip pain. PS is frequently overlooked in clinical field because its symptoms are similar to that of primary sacral dysfunction, or lumbar radiculopathy. Thus exact diagnosis is very important. The piriformis muscle cross-sectional area (PMCSA) has not yet been proven to be an independent risk factor for the diagnosis of PS. The present study analyze the relationship between the PMCSA and PS. We hypothesized that PMCSA is a key diagnostic parameter in the PS. Both PMCSA and piriformis muscle thickness (PMT) samples were obtained from 30 patients with PS, and from 30 healthy individuals who underwent hip magnetic resonance imaging (H-MRI) with no evidence of PS. T1W H-MRI images were obtained. We investigated the PMCSA and PMT on H-MRI using a PACS system. The PMCSA was measured in coronal sections of the entire image by contour drawing. The PMT was measured primarily based on the hypertrophied piriformis muscle. Both PMCSA and PMT were significantly associated with PS, but PMCSA was measured as a much more sensitive parameter. Therefore, to evaluate patients with PS, physicians should examine PMCSA more carefully than PMT. The average PMCSA was 564.36 ± 121.61 mm2 in the normal group and 736.88 ± 168.87 mm2 in the PS group. The average PMT was 13.83 ± 2.61 mm in the control group and 15.99 ± 2.34 mm in the PS group. PS group had significantly higher PMCSA (P≤.001) and PMT (P≤.001). Regarding the validity of both PMCSA and PMT as predictors of PS, receiver operating characteristic curve analysis showed the best cutoff point for the PMCSA was 611.67 mm2, with 75.0% specificity, 75.0% sensitivity, and the AUC of 0.81 (95% CI 0.68–0.94). The best cutoff value of the PMT was 14.24 mm, with 70.0% sensitivity, 70.0% specificity, and the AUC of 0.78 (95% CI 0.63–0.93).
Analgesic therapy failure in a COMT HPS/HPS diplotype carrier heterozygous for the CYP2D6 *4 allele with fibromyalgia—a case report
Authors: Bollinger Anna , Gianora Julia , Schüpbach Tanja , Allemann Samuel S. , Stäuble Céline K. , Meyer zu Schwabedissen Henriette E.
Published: February 2025

Introduction:

The cytochrome P450 enzyme 2D6 (CYP2D6) and the catechol-O-methyltransferase (COMT) enzyme are involved in catecholamine metabolism, potentially influencing pain modulation. Catechol-O-methyltransferase has 3 major haplotypes related to pain sensitivity: low (LPS), average (APS), and high (HPS). However, the reliability of these haplotypes in predicting clinical outcomes is not well investigated. We present a 40-year-old female patient with fibromyalgia. Despite extensive pharmacotherapy with 120 mg/d duloxetine, 150 mg/d pregabalin, 80 mg/d oxycodone, 2 g/d paracetamol, and 1.6 g/d ibuprofen, she suffered from severe pain.

Objectives:

We aim to investigate the patient’s susceptibility to analgesic therapy failure (TF) and pain sensitivity with pharmacogenotyping.

Methods:

PGx panel testing, including CYP2D6 and COMT rs4680, was conducted by a commercial provider. Additional genotyping of COMT rs6269, rs4633 and rs4818 was performed applying PCR, restriction fragment length polymorphism assay and sanger sequencing.

Results:

The patient was identified as COMT HPS/HPS diplotype carrier and CYP2D6 intermediate metabolizer. CYP2D6 is mainly responsible for the bioactivation of oxycodone into oxymorphone. Reduced CYP2D6 activity may result in a lower oxycodone activation. Considering the coadministration of duloxetine (a moderate CYP2D6 inhibitor), the TF of oxycodone could also be the result of a drug–drug–gene interaction. No other medications were affected by her genetic profile.

Conclusion:

We hypothesize that the broad TF of pain medications and associated high pain sensitivity could be related to the patient’s genetic predisposition in CYP2D6 and COMT, warranting further investigation in a larger patient sample.
One-Stop 68Ga-FAPI/18F-FDG Total-Body PET/CT Scan
Authors: Gao Huaping , Tang Han , Zheng Zhe , Yu Haojun , Mao Wujian , Lin Yu , Zheng Jiefu , Al-Ibraheem Akram , He Yibo , Tang Wenxin , Yang Runjun , Xie Yunze , Tan Lijie , Shi Hongcheng
Published: February 2025

Purpose:

This prospective study aims to assess the feasibility of a one-stop imaging protocol using 68Ga-FAPI-04/18F-FDG dual-radiotracer with dual-low-activity for tumor imaging.

Patients and Methods:

Forty patients underwent one-stop 68Ga-FAPI-04 PET (PETFAPI) and dual-radiotracer PET (PETDUAL) using a total-body PET/CT scanner with a 194-cm axial field of view. After a half-dose (0.925 MBq/kg) 68Ga-FAPI-04 PET/CT, an additional half-dose (1.85 MBq/kg) of 18F-FDG was administered for a 60-minute dynamic acquisition. PETDUAL was reconstructed at 10-minute intervals (PETD0–10, PETD10–20, PETD20–30, PETD30–40, PETD40–50, and PETD50–60). Data of lesion detectability, target-to-background ratios, tumor staging, and total radiation dose were analyzed. A target-to-liver ratio (TLR) ≥ 3 on PETFAPI was considered indicative of sufficient fibroblast activation protein expression.

Results:

PETD50–60 and PETFAPI showed similar performance in detecting primary tumors (42 vs 41, P > 0.999). However, significantly more metastatic lesions were identified on PETD50–60 compared with PETFAPI (102 vs 60, P < 0.001). PETFAPI demonstrated significantly higher TLR, target-to-blood-pool ratio, and target-to-normal-tissue ratio than PETDUAL (P < 0.05). Lesion detectability was similar across PETD10–20, PETD20–30, PETD30–40, PETD40–50, and PETD50–60 (all P’s > 0.05). Notably, PETD30–40 and PETD40–50 detected all lesions identified by PETD50–60. PETD40–50 showed no significant differences in TLR, target-to-blood-pool ratio, and target-to-normal-tissue ratio compared with PETD50–60 (P > 0.05). Up to 94.9% of malignant primary lesions exhibited a TLR ≥ 3 on PETFAPI. The average effective dose was 9.85 ± 2.19 mSv, similar to that of a whole-body 18F-FDG PET/CT.

Conclusions:

This one-stop, dual-radiotracer, dual-low-activity imaging protocol combines the strengths of 68Ga-FAPI-04 and 18F-FDG, offering a shorter imaging duration and reduced radiation exposure.
A Merkel Cell Carcinoma of the Face
Authors: Teng YongXiang , Fu Yanjie , Su Gang , Mu Zelan , Zhang Jian , Zhai Zhaohui , Li Yuli
Published: February 2025

Merkel cell carcinoma (MCC) is a rare, invasive cutaneous neuroendocrine carcinoma that is more commonly seen in older people. It has characteristics of a high metastasis rate, high recurrence rate, and low survival rate. The clinical features of MCC are not obvious, making it easy to confuse with other malignant skin tumors. At present, there is no clear and established treatment plan for MCC, which poses a significant challenge in clinical practice. In this paper, through the report of MCC-related cases and a review of the relevant literature, the diagnosis and treatment of MCC were discussed, providing a reference for clinicians in treating MCC.
Original Study: Association of High-Deductible Health Plans and Complicated Appendicitis among Children
Authors: Rook Jordan M. , Kelley-Quon Lorraine I. , Jen Howard C. , Gidwani Risha
Published: February 2025

Objective:

To determine whether high-deductible health plans (HDHPs) are associated with complicated disease and hospitalization costs for children with appendicitis.

Background:

Nearly 60% of families with non-governmental employer-sponsored insurance are enrolled in high-deductible health plans (HDHPs). It is unknown how these plans affect children who require surgical care.

Methods:

This retrospective cohort study used the 2016-2020 MarketScan dataset. We included children aged 17 years and younger with non-governmental employer-sponsored insurance who were treated for acute appendicitis. The exposure was a binary variable indicating family enrollment in a HDHP. We assessed the outcomes of complicated appendicitis and hospitalization costs. We used machine learning-based propensity score weights and multivariable regression to assess the association between HDHP enrollment and outcomes. Covariates included age, gender, geographic region, comorbidities, prior healthcare utilization, and month and year treated.

Results:

Of 18,291 children treated for appendicitis, 40.6% (n=7,434) were enrolled in HDHPs. Groups exhibited covariate balance after propensity score weighting. HDHP enrollment was associated with a 2.6 percentage point (95%CI, 1.2-3.9; P<0.001) increase in the likelihood of presenting with complicated appendicitis (33.2% versus 30.6%); a $2,491 (95%CI, $2,428-$2,555; P<0.001) increase in out-of-pocket costs ($4,341 versus $1,850); and a $703 (95%CI, $185-$1,222; P=0.008) increase in total costs ($24,556 versus $23,852).

Conclusions:

Children in HDHPs more often present with complicated appendicitis and require more costly hospitalizations. High levels of cost sharing, a dominant component of most private insurance plans, may not serve the needs of children with acute illnesses and can increase costs to patients and society.
Computational Platform for streamlining the success of sequential antibiotic therapy
Authors: Anderson Alejandro , Kinahan Matt , Blanco-Rodríguez Rodolfo , Gonzalez Alejandro H. , Udekwu Klas , Hernandez-Vargas Esteban A.
Published: February 2025

The scarcity of antibiotics and the need for swift decision-making present significant challenges for healthcare practitioners. When confronted with such circumstances, practitioners must prioritize their approach based on several key factors. By leveraging the recent biological discovery of collateral sensitivity, we have devised an open-source computational platform. This platform utilizes the drug resistance profile of an evolved strain and initial population conditions to potentially predict the failure of cycling therapy in eradicating or restraining a multi-drug resistant bacterial population. We demonstrate how this framework can anticipate potential failures for a range of antibiotics in chronicpseudomonas aeruginosainfections. This innovative methodology lays the foundation for evolutionary therapies that can facilitate the selection of appropriate treatments, thereby reducing antibiotic resistance.
MYBPC3(c.194C>T) mutation-mediated RyR2 dysfunction contributes to pathogenic phenotypes of dilated cardiomyopathy revealed by hiPSC modeling
Authors: Xie Manting , Xie Bingbing , Chen Ying , Lai Xingqiang , Gong Jixing , Cao Nan , Xiang Andy Peng , Xiang Qiuling
Published: February 2025

Dilated cardiomyopathy (DCM) is a leading cause of heart failure and the primary indication for heart transplantation. The intricate and poorly elucidated pathogenesis of genetic DCM, coupled with the paucity of effective therapeutic options, imposes a substantial burden on both patients and their families. In this study, we identified a novelMYBPC3mutation (c.194C>T) in a patient diagnosed with DCM and established a patient-specific human induced pluripotent stem cell (hiPSC) model. Cardiomyocytes derived from these patient-specific hiPSCs (hiPSC-CMs) exhibited hallmark features of DCM, including hypertrophic cell size, aberrant distribution of sarcomeric α-actinin, and dysregulated calcium ion homeostasis, as compared to control hiPSC-CMs derived from a healthy individual. RNA sequencing analysis revealed a significant upregulation ofCASQ2, which encodes calsequestrin, a protein that binds to Ryanodine receptor 2 (RyR2). Notably, treatment with the RyR2 inhibitor ryanodine effectively restored the abnormal calcium transients observed in DCM-hiPSC-CMs. In summary, our findings provide compelling evidence that the c.194C>T mutation ofMYBPC3plays a definitive pathogenic role in DCM, and that modulation of the RyR2 receptor may alleviate calcium dysregulation in affected cardiomyocytes. These insights enhance our understanding of the molecular mechanisms underlying DCM and offer a promising therapeutic strategy for patients with calcium ion dysregulation associated with this condition.

Graphical Abstract

Highlights

Cardiomyocytes differentiated from patient-specific induced pluripotent stem cells (hiPSCs) reproduces morphology of cardiac hypertrophy and sarcomeric disorders.

novelc.194C>Tmutation inMYBPC3results in abnormal calcium transients in hiPSC-derived cardiomyocytes.

c.194C>Tmutation ofMYBPC3leads to a significant increase in the expression of calsequestrin that binds to the ryanodine receptor 2 (RyR2).

with RyR2 inhibitor markedly improves the ability of calcium handling in DCM-hiPSC-cardiomyocytes.
Clinical audit on laboratory diagnosis of malaria parasites at Jimma University Medical Center laboratory, Southwest Ethiopia
Authors: Girma Dechasa , Hailu Adane , Abebe Chalachew , Said Hawa , Mohamoud Hamda , Asaye Sintayehu
Published: February 2025

1.

Background

Microscopic diagnosis using stained blood films is usually regarded as the gold standard and most acceptable method of diagnosis. There is no clinical audit performed at the Clinical Laboratory of Jimma University Medical Center, which aims to audit malaria diagnosis; therefore, this audit assesses the pre-analytic, analytic, and post-analytic processes that can affect the accuracy and quality of malaria diagnosis in this laboratory against the established acceptable standards of malaria diagnosis.

Method

We conducted a clinical audit at the Jimma University Medical Center Laboratory from January 2-20, 2025, using direct observation of the procedure that laboratory staff follow in blood collection, fixation, blood smear preparation, microscopic examination, reporting, and documentation of malaria diagnosis results, and also by re-examining the diagnosed slides to assess the skill of laboratory staff by maintaining confidentiality of the data.

Results

A total of 26 quality standards were used. It is known that 56.3 percent of the samples are collected from capillaries and 43.7 from veins. Approximately 78 percent of the samples were collected from properly rubbed fingers and 22% from fingers that were not rubbed adequately. All the blood samples collected with an anticoagulant were mixed properly before smearing (n=35), 78.8 % of the slides were preliminarily visualized using a high-power (100x) objective of the microscope, and only 17.5 % of the slides were visualized using a 10x objective.

Conclusion

Proper Disinfection, mixing the anti-coagulated blood well, and fixing thin blood films for the recommended length of time were areas of good practice. On the other hand, failure to report parasitic load and proper and sequential use of types of objectives to examine blood films and prepare smears of good quality were some of the highly violated standards that need consideration.
Adaptations of gram-negative and gram-positive probiotic bacteria in engineered living materials
Authors: Tadimarri Varun Sai , Tyagi Tanya Amit , Duong Cao Nguyen , Rasheed Sari , Müller Rolf , Sankaran Shrikrishnan
Published: February 2025

Encapsulation of microbes in natural or synthetic matrices is a key aspect of engineered living materials, although the influence of such confinement on microbial behavior is poorly understood. A few recent studies have shown that spatial confinement and mechanical properties of the encapsulating material significantly influence microbial behavior, including growth, metabolism, and gene expression. While such effects have been shown to elicit various responses in a few micro-organisms likeE. coli, yeast, and cyanobacteria, systematic comparative studies between different organisms in the same confinement conditions are missing. Thus, in this study, we report the adaptive responses exhibited by rod-shaped gram-negative and gram-positive probiotic bacteria that are of great interest for developing therapeutic engineered living materials. Accordingly, gram-negativeE. coliNissle 1917 and gram-positiveL. plantarumWCFS1 were encapsulated in hydrogel matrices and their growth, metabolic activity, and recombinant gene expression were investigated. By varying the polymer concentration and degree of chemical cross-linking in the hydrogels, it was possible to modulate their stiffness and study how the bacteria adapted to these different confinement conditions. In accordance with previous reports, both bacteria grow from single cells into confined colonies but more interestingly, inE. coligels, mechanical properties influenced colony growth, size, and morphology, whereas this did not occur inL. plantarumgels. However, with both bacteria, increased matrix stiffness led to higher levels of recombinant protein production within the colonies. By measuring metabolic heat generated in the bacterial gels using a novel isothermal microcalorimetry technique, it was inferred thatE. coliadapts to the mechanical restrictions through multiple metabolic transitions and is significantly affected by the different hydrogel properties. Contrastingly, both these aspects were not observed withL. plantarum. These results revealed that despite both these bacteria being gut-adapted probiotics with similar geometries, mechanical confinement affects them considerably differently. The weaker influence of matrix stiffness onL. plantarumis attributed to its slower growth and thicker cell wall possibly enabling the generation of higher turgor pressures to overcome restrictive forces under confinement. By providing fundamental insights into the interplay between mechanical forces and bacterial physiology, this work advances our understanding of how matrix properties shape bacterial behavior. The implications of these findings will aid the design of engineered living materials for therapeutic applications.
Magnetic printing and actuation of stretchable muscle tissue
Authors: Demri Noam , Morizur Lise , Dumas Simon , Gropplero Giacomo , Martinat Cécile , Descroix Stéphanie , Wilhelm Claire
Published: February 2025

While the link between tissue organization, stimulation, and function is now acknowledged as crucial for tissue development, engineering tissues with precise, long-lasting shapes and the capability for mechanical stimulation remains challenging. This study addresses this challenge by developing a next-generation magnetic bioprinting approach to create anisotropic, shape-controlled, scaffold-free, and stretchable skeletal muscle constructs.

Murine skeletal muscle cells and human induced pluripotent stem cell-derived skeletal muscle cells, labeled with iron oxide nanoparticles, were magnetically bioprinted into wrench-shaped tissues. Their magnetic properties allowed these tissues to be clipped onto magnetic needles, preserving their shape over two weeks of culture while promoting anisotropic differentiation and myoblast fusion. Additionally, the magnetic tissues could be stretched by up to 100%, enhancing their anisotropy and improving muscle maturation.

This magnetic toolbox demonstrates significant advancements in muscle tissue engineering, as evidenced by enhanced indicators of myoblast differentiation, including cell fusion, increased myogenic maturation and contractility. These findings highlight the potential of magnetic-based techniques for developing advanced muscle-on-chip systems and other complex tissue constructs.
Sequencing by Expansion (SBX) – a novel, high-throughput single-molecule sequencing technology
Authors: Kokoris Mark , McRuer Robert , Nabavi Melud , Jacobs Aaron , Prindle Marc , Cech Cynthia , Berg Kendall , Lehmann Taylor , Machacek Cara , Tabone John , Chandrasekar Jagadeeswaran , McGee Lacey , Lopez Matthew , Reid Tommy , Williams Cara , Barrett Salka , Lehmann Alex , Kovarik Michael , Busam Robert , Miller Scott , Banasik Brent , Kesic Brittany , Arryman Anasha , Rogers-Peckham Megan , Kimura Alan , LeProwse Megan , Wolfin Mitchell , Kritzer Svetlana , Leadbetter Joanne , Babazadeh Majid , Chase John , Thiessen Greg , Lint William , Goodman Drew , O’Connell Dylan , Lumanpauw Nadya , Hoffman John , Vellucci Samantha , Collins Kendra , Vellucci Jessica , Taylor Amy , Murphy Molly , Lee Michael , Corning Matthew
Published: February 2025

Remarkable advances in high-throughput sequencing have enabled major biological discoveries and clinical applications, but achieving wider distribution and use depends critically on further improvements in scale and cost reduction. Nanopore sequencing has long held the promise for such progress, but has had limited market penetration. This is because efficient and accurate nanopore sequencing of nucleic acids has been challenged by fundamental signal-to-noise limitations resulting from the poor spatial resolution and molecular distinction of nucleobases. Here, we describe Sequencing by Expansion (SBX), a single-molecule sequencing technology that overcomes these limitations by using a biochemical conversion process to encode the sequence of a target nucleic acid molecule into an Xpandomer, a highly measurable surrogate polymer. Expanding over 50 times longer than the parent DNA templates, Xpandomers are engineered with high signal-to-noise reporter codes to enable facile, high-accuracy nanopore sequencing. We demonstrate the performance of SBX and present the specialized molecular structures, chemistries, enzymes and methods that enable it. The innovative molecular and systems engineering in SBX create a transformative technology to address the needs of existing and emerging sequencing applications.
Evaluation of the Irritation and Sensitization Potential of Medical-grade Norway Spruce (Picea abies) Resin Salve: Single-Blind Modified Draize Repeat Insult Patch Test in Healthy Volunteers
Authors: Yamileva Kamilla , Multia Evgen
Published: February 2025

Background

Abilar® is a wound salve containing 10 % medical-grade Norway spruce (Picea abies) resin, known for its antimicrobial and wound-healing properties. However, isolated reports of allergic contact dermatitis have raised concerns regarding its cutaneous safety profile. Given the increasing use ofPicea abiesresin-based products, it is important to evaluate any potential for skin irritation and sensitization.

Objectives

To evaluate the irritation and sensitization potential of medical-gradePicea abiesresin salve using a modified Draize Human Repeat Insult Patch Test (HRIPT) in a healthy adult cohort, thereby providing toxicological insights relevant to both clinical applications and consumer safety.

Methods

A single-blind study (ClinicalTrial.gov, Identifier:NCT06810856) was conducted with 215 healthy volunteers (207 completed the study). Medical-gradePicea abiesresin salve was applied through cutaneous patches in an induction phase and a challenge phase. Skin reactions were evaluated using modified Draize scoring system, with reactions to both the test material and adhesive being recorded separately.

Results

During the induction phase, only 7 of 207 subjects (3.38%) of participants exhibited mild erythema (Grade 1) attributed to the resin salve. Notably, no participant experienced moderate to severe reactions (Grades 2–5). In the subsequent challenge phase, no reactions were observed, and subjects with prior Grade 1 responses reverted to a non-reactive status. These findings indicate that, under the test conditions and repeated exposure regimen, the medical-gradePicea abiesresin salve demonstrates a low potential for inducing cutaneous irritation or sensitization.

Conclusions

The HRIPT findings demonstrate that medical-gradePicea abiesresin salve has a low irritation and sensitization potential under the conditions tested. Although rare cases of allergic contact dermatitis have been documented in literature in predisposed individuals, the data of this study suggests that the overall risk in the general population is low. These findings are also supported by clinical studies and extensive post-market surveillance of Abilar® in wound care for both acute and chronic wounds.

Graphical Abstract
Chronic adaptive versus conventional deep brain stimulation in Parkinson’s disease: a blinded randomized pilot trial
Authors: Isaias Ioannis U. , Marceglia Sara , Borellini Linda , Mailland Enrico , Cogiamanian Filippo , Barbieri Sergio , Ampollini Antonella , Pirola Elena , Remore Luigi , Caffi Laura , Palmisano Chiara , Baiata Claudio , Bonvegna Salvatore , Romito Luigi , Eleopra Roberto , Levi Vincenzo , Bentivoglio Anna Rita , Piano Carla , Izzo Alessandro , Zibetti Maurizio , Lopiano Leonardo , Lanotte Michele , Mandat Tomasz , Tamma Filippo , Arlotti Mattia , Conti Costanza , Rossi Lorenzo , Foffani Guglielmo , Lozano Andres , Moro Elena , Volkmann Jens , Locatelli Marco , Priori Alberto
Published: February 2025

Background

Adaptive deep brain stimulation (aDBS) is becoming a feasible therapeutic option in patients who are candidates for DBS, and implantable devices are now commercially available. We present the results of a blinded, randomized, crossover pilot trial aimed at comparing aDBS with conventional DBS (cDBS).

Methods

Fifteen patients were implanted with the AlphaDBS device (Newronika SpA, Milan, Italy,NCT04681534). The device replaced a previous Medtronic Activa PC at battery depletion in 11 patients, while the other four were first-time implant patients. Patients underwent two study phases: 1) a two-day, short-term follow-up in the hospital, in which patients received aDBS and cDBS for one day each (in random order); 2) a one-month, long-term follow-up at home, with patients receiving both DBS modes, each for two weeks. Safety endpoints were the occurrence of stimulation-related adverse events and the total electrical energy delivered to the tissue. The clinical endpoints were the Unified Parkinson’s (part III) and Dyskinesia Disease Rating Scales used for in-clinic evaluation, and a three-day diary used for home assessment to estimate good on time without troublesome dyskinesia. At the end of the study, patients blindly decided their preferred stimulation mode.

Findings

No related adverse events were reported. The AlphaDBS device reliably recorded deep brain signals and applied a linear algorithm that changed the stimulation current every minute based on the average local field potential amplitude, calculated in a patient-specific beta frequency range. In the short-term follow-up, aDBS improved patients as much as cDBS, with lower UDysRS scores. In the long-term follow up, considering intra-patient differences, aDBS provided greater benefit than cDBS in 80% of patients. The same percentage of patients preferred and continued with aDBS (mean follow-up 316 days).

Interpretation

Our results suggest that aDBS is safe and effective and can be applied in a large population of parkinsonian patients who are candidates for DBS. The majority of patients improved more with aDBS than cDBS, who subjectively preferred aDBS in the long term. Further research is needed to better understand the profile of the best responders and the scheduling of aDBS.
A standardised saffron extract improves subjective and objective sleep quality in healthy older adults with sleep complaints: results from the Gut-Sleep-Brain Axis randomised, double-blind, placebo-controlled pilot study
Authors: Lang Leonie , Ditton Annabel , Stanescu Andi , Jainani Vernisse , McArthur Simon , Pourtau Line , Gaudout David , Pontifex Matthew G. , Tsigarides Jordan , Steward Taylor , Sami Saber , Muller Michael , Hornberger Michael , Vauzour David , Lazar Alpar S.
Published: February 2025

Sleep disorders may increase neurodegenerative diseases risks and alter gut microbiota composition. Saffron (Crocus sativus) supplementation has been linked to sleep improvements and gut microbiome changes, but its effect on sleep quality through gut microbiota-brain axis modulation remains unexplored. A randomised, placebo-controlled pilot study of saffron (30mg/day for 4-weeks) was conducted with 52 older adults (55-85 years) experiencing sleep complaints. Subjective and objective sleep quality were measured using validated questionnaires and electroencephalography-based sleep tracker respectively. A subgroup (n=26) underwent microbiome analysis. Saffron supplementation improved subjective sleep quality (p=0.02) and sleep efficiency (p=0.04). Objective measures showed reduced latency to persistent sleep (p=0.003) and sleep onset latency (p=0.03). Linear discriminant analysis effect size analysis of the microbiome revealed increases inFaecalibacterium(q=0.013),Lachnoclostridium(q=0.045),Prevotella(q=0.022),UBA1819(q=0.020) andOscillibacter(q=0.045), while decreasingDialister(q=0.028). Univariate analysis further indicated increases inLachnospiraceae-UGC-001(p=0.020) andRoseburia(p=0.03), with a decrease inTuricibacter(p=0.045) in the saffron group.OscillibacterandUBA1819correlated with subjective measures of sleep efficiency (r=0.63, p=0.0007) and sleep latency (r=-0.39, p=0.04. Changes inDialister, TuricibacterandUBA1819were correlated with several measures of objective sleep quality including wake duration, latency to persistent sleep and wake-after-sleep-onset. Four-weeks saffron supplementation improved both subjective and objective sleep quality in older adults with sleep complaints, while increasing gut bacteria that produce short-chain fatty acids. These results pave the way for further randomised controlled trials exploring the links between sleep quality and gut health and may help devising new preventative strategies for age-related brain disorders.
Tahoe-100M: A Giga-Scale Single-Cell Perturbation Atlas for Context-Dependent Gene Function and Cellular Modeling
Authors: Zhang Jesse , Ubas Airol A , de Borja Richard , Svensson Valentine , Thomas Nicole , Thakar Neha , Lai Ian , Winters Aidan , Khan Umair , Jones Matthew G. , Tran Vuong , Pangallo Joseph , Papalexi Efthymia , Sapre Ajay , Nguyen Hoai , Sanderson Oliver , Nigos Maria , Kaplan Olivia , Schroeder Sarah , Hariadi Bryan , Marrujo Simone , Salvino Crina Curca Alec , Gallareta Olivares Guillermo , Koehler Ryan , Geiss Gary , Rosenberg Alexander , Roco Charles , Merico Daniele , Alidoust Nima , Goodarzi Hani , Yu Johnny
Published: February 2025

Building predictive models of the cell requires systematically mapping how perturbations reshape each cell’s state, function, and behavior. Here, we presentTahoe-100M, a giga-scale single-cell atlas of 100 million transcriptomic profiles measuring how each of 1,100 small-molecule perturbations impact cells across 50 cancer cell lines. Our high-throughput Mosaic platform, composed of a highly diverse and optimally balanced “cell village”, reduces batch effects and enables parallel profiling of thousands of conditions at single-cell resolution at an unprecedented scale.

As the largest single-cell dataset to date,Tahoe-100Menables artificial-intelligence (AI)-driven models to learn context-dependent functions, capturing fundamental principles of gene regulation and network dynamics. Although we leverage cancer models and pharmacological compounds to create this resource,Tahoe-100Mis fundamentally designed as a broadly applicable perturbation atlas and supports deeper insights into cell biology across multiple tissues and contexts. By publicly releasing this atlas, we aim to accelerate the creation and development of robust AI frameworks for systems biology, ultimately improving our ability to predict and manipulate cellular behaviors across a wide range of applications.
IMPDH Cytoophidia in the Pancreas: Morphological Dynamics and Metabolic Implications
Authors: Huang Yujie , Liu Ji-Long , Zhang Wenchuan
Published: February 2025

Cytoophidia are filamentous structures formed by metabolic enzymes, playing critical roles in cellular metabolism and regulation. Inosine monophosphate dehydrogenase (IMPDH), the rate-limiting enzyme in de novo nucleotide synthesis, is known to form cytoophidia and is implicated in cell proliferation, nutrient sensing, and metabolic stress responses. Despite their significance, the behavior of IMPDH cytoophidia under different metabolic conditions, particularly in diabetes, remains poorly understood. This study investigates the distribution, morphology, and assembly patterns of IMPDH cytoophidia in the pancreas of normal and diabetic models. Using immunofluorescence staining, pharmacological interventions (e.g., mycophenolic acid), and glucose tolerance tests, we demonstrate that IMPDH cytoophidia exhibit distinct morphological changes in pancreatic islets under diabetic conditions. Notably, cytoophidia elongation is associated with impaired glucose tolerance, suggesting a potential link between cytoophidia dynamics and metabolic dysfunction. Our findings provide novel insights into the role of IMPDH cytoophidia in metabolic regulation and highlight their potential as therapeutic targets for diabetes and related metabolic disorders.
Progression GWAS followed by functional characterization implicates E3 ubiquitin ligaseTRIM2as a potential genetic modifier of Parkinson’s disease progression
Authors: Kulkarni Ameya S. , Apicco Dan , Tamim Saleh , Gibilisco Lauren , Nahlawi Layan , Lucia Rachel , Ghosh Sujana , Lent Samantha , Liang Yanyu , Khasnavis Saurabh , Smith Laura , Stender Joshua , Vijay Priyanka , Zadikoff Cindy , Davis Justin Wade , Stoehr Jan , Noh Hyun Ji
Published: February 2025

Parkinson’s Disease (PD) is a progressive neurodegenerative disorder, affecting 10 million people worldwide. While genome-wide association studies (GWAS) have identified many genetic variants associated with PD incidence, the genetics underlying PD progression are poorly understood. Here, we aim to address this gap by performing GWAS on longitudinal clinical metrics from well-defined PD cohorts. Specifically, we identify 8 novel GWAS genes for PD progression, includingTRIM2,which encodes an E3 ubiquitin ligase with loss-of-function mutations that cause neuropathy. Functional genomics data suggest that the GWAS SNPs in the locus ofTRIM2regulate its expression across several PD-relevant brain regions. Further, we show thatTRIM2knockdown and overexpression in primary neurons regulate neurofilament light (NF-L) levels and α-synuclein aggregation-the primary neuropathological hallmark of PD. Peripheral proteomic analysis of a genetically defined PD patient cohort demonstrates increased NF-L protein levels in the plasma and cerebrospinal fluid ofTRIM2SNP carriers, corroborating the role of TRIM2 in NF-L regulation. Overall, by integrating PD progression GWAS with transcriptomic, eQTL analyses, and functional data in PD cellular models, we identify new targets includingTRIM2that may influence the progression rate of PD.
Prevalence of screening HIV among LGBTQ+ at Ramathibodi Hospital
Authors: Chuenpakorn Nunticha , Chaisoksombat Kewalin , Siriyotha Sukanya , Chuenpakorn Nanthiphat , Arunakul Jiraporn , Maude Rapeephan R.
Published: February 2025

Background

LGBTQ+ individuals face significant barriers in accessing healthcare services, particularly in relation to HIV screening. This study investigates the prevalence of HIV testing among LGBTQ+ individuals and explores factors influencing healthcare-seeking behaviors at Ramathibodi Hospital in Bangkok, Thailand.

Methods

A cross-sectional survey was conducted among 300 self-identified LGBTQ+ individuals aged 18 and older who recently utilized outpatient services at Ramathibodi Hospital. Data were collected via an online questionnaire assessing demographic characteristics, sexual behaviors, and attitudes toward public health services. Univariate and multivariate logistic regression analyses were performed to identify factors associated with HIV testing.

Results

HIV testing prevalence among participants was 45%, with significant associations found between HIV testing and gender identity, age, and engagement in sexual activity. Gay participants (OR = 21.73, 95% CI: 4.73–99.90, p < 0.001) and transgender females (OR = 7.51, 95% CI: 2.08–27.34, p = 0.002) were more likely to undergo HIV testing compared to other groups. Those aged 30 years or older (OR = 2.50, 95% CI: 1.43– 4.34, p = 0.001) and those engaging in sexual activity (OR = 4.58, 95% CI: 2.52–8.33, p < 0.001) were also more likely to be tested. Participants reported mixed experiences regarding the inclusivity of healthcare environments, with a desire for improved LGBTQ+ cultural competence among healthcare workers.

Conclusion

While HIV testing rates are relatively high among certain LGBTQ+ subgroups, significant gaps remain, particularly for transgender males. The study highlights the need for targeted outreach and healthcare interventions to increase HIV screening among underserved populations. Expanding LGBTQ+ cultural competency in healthcare settings is crucial to ensure inclusive and respectful care.
Transmission thresholds for the spread of infections in healthcare facilities
Authors: Toth Damon J.A. , Khader Karim , Mitchell Christopher , Samore Matthew H.
Published: February 2025

Some infections may be sustained in the human population by persistent transmission among patients clustered in healthcare facilities, including patients colonized with multi-drug-resistant organisms posing a major health threat. A nuanced understanding of facility characteristics that contribute to crossing a threshold for self-sustaining outbreak potential may be crucial to designing efficient interventions for lowering regional disease burden and preventing infections among high-risk patients. Using a mathematical model, we define the facility basic reproduction numberR0, where a single facility can sustain an outbreak without ongoing importation under the threshold conditionR0> 1. We defineR0for a general model with heterogeneous patient states of susceptibility and transmissibility and with generic length-of-stay assumptions, and we provide a software package for numerical calculation of user-defined examples. We estimateR0using published data for carbapenemase–producing Enterobacteriaceae (CPE) in longterm acute-care hospitals (LTACHs) and the effects of interventions onR0, including surveillance, pathogen reduction treatments, and length-of-stay reduction. In a simple model,R0is directly proportional to the sum of the mean and variance-to-mean ratio of the length-of-stay distribution. In intervention models,R0depends on the moment-generating function of the length-of-stay distribution. From the CPE data, we estimatedR0= 1.24 (95% CI: 1.04, 1.45) prior to intervention. Weekly surveillance with 50% transmission reduction of detected patients alone could have reducedR0to 0.85 (0.72, 0.98), with additional reduction if detected patients could be decolonized. Reducing the mean length of stay does not necessarily reduceR0if the variance-to-mean ratio is not also reduced. We conclude thatR0>1 conditions plausibly exist in LTACHs, where CPE outbreaks could be sustained by patients who acquire colonization and subsequently transmit to other patients during the same hospital stay. Our findings illuminate epidemiological mechanisms producing those conditions and their relationship to interventions that could efficiently improve population health.
Synaptotoxic effects of extracellular tau are mediated by its microtubule-binding region
Authors: Ondrejcak Tomas , Hu Neng-Wei , Coode Emily , Campbell Tom , Corbett Grant T. , Doykov Ivan , Mills Kevin , Walsh Dominic M. , Livesey Frederick J. , Rowan Michael J. , Klyubin Igor
Published: February 2025

Immunotherapies targeting extracellular tau share the premise that interrupting cell-to-cell spread of tau pathology in Alzheimer’s disease (AD) will slow dementia pathogenesis. How these interventions affect the actions of synaptotoxic, extracellular tau species that may help mediate cognitive impairment is relatively unknown. Here, we assayed synaptic plasticity disruption in anaesthetised live rats caused by intracerebral injection of synaptotoxic tau present either in (a) secretomes of induced pluripotent stem cell-derived neurons (iNs) from people with Trisomy 21, the most common genetic cause of AD, or (b) aqueous extracts of human AD brain. Extracellular tau in iN secretomes was found to include fragments that contain the extended microtubule binding regions of tau, MTBR/R’ and adjacent C-terminal peptides. Immunodepletion or co-injection with antibodies targeting epitopes within these fragments prevented the acute disruption of synaptic plasticity by these patient-derived synaptotoxic tau preparations. Conversely, a recombinant human tau fragment encompassing the core MTBR/R’- region present in tau fibrils, tau297-391 potently mimicked this deleterious action of patient-derived tau. MTBR/R’-directed antibodies also rapidly reversed a very persistent synaptotoxic effect of soluble brain tau. Our findings reveal a hitherto relatively unexplored potential benefit of targeting MTBR/R’.
Earlier menopause is associated with both reduced cognitive performance and gray matter volume: a population-based cross-sectional study
Authors: Schwarz Nitsan , Harlev Daniel , Bergmann Eyal , Wolpe Noham
Published: February 2025

Background

Age at menopause varies widely across women, yet little is known about how this relates to long-term behavioral and brain-structural changes. Previous research has focused primarily on the menopausal transition itself, and the few studies investigating cognitive outcomes suggest reduced age-related cognitive performance with earlier menopause.

Objectives

This study aims to investigate whether earlier menopause onset is associated with reduced cognitive performance and brain structure in later-life, in the same cohort of postmenopausal women.

Methods

We analyzed data from the Cambridge Centre of Neuroscience and Aging, which included 747 postmenopausal women who underwent cognitive testing (Addenbrooke’s Cognitive Examination Revised, ACE-R). A subset (n=188) was additionally tested with a fluid intelligence test and underwent structural brain scans to measure gray and white matter volume (GMV and WMV). Multiple linear regression models were used to evaluate the association between menopause age and cognitive performance, as well as grey matter volume, controlling for chronological age.

Results

Earlier menopause onset was associated with lower cognitive performance, as measured by the ACE-R (t(719)=2.81,p=0.005). Similar results were found for fluid intelligence (t(146) = 3.116,p=0.002). Structural brain analyses showed that a reduction of one year at the age of menopause onset was associated with a reduction of 2370mm3in total grey matter volume (t(182)=3.37,p=0.001). No significant interactions were observed between menopause onset age and chronological age for any of the outcomes. GMV was a partial mediator between age at menopause onset and cognitive performance, while controlling for age.

Conclusion

Women with earlier menopause show both reduced cognitive performance and lower GMV, suggesting that GMV reduction may be one mechanism linking earlier menopause to cognitive decline. However, the cross-sectional nature of this study prevents causal conclusions, and longitudinal research is needed to establish causal links and to explore potential targeted interventions.
Machine Learning Prediction of Non-Coding Variant Impact in Cell-Class-Specific Human RetinalCis-Regulatory Elements
Authors: VandenBosch Leah S. , Cherry Timothy J.
Published: February 2025

Non-coding variants in cis-regulatory elements such as promoters and enhancers contribute to inherited retinal diseases (IRDs), however, characterizing the functional impact of most regulatory variants remains challenging. To improve identification of variants of interest, we implemented machine learning using a gapped k-mer support vector machine approach trained on single nucleus ATAC-seq data from specific cell classes of the adult and developing human retina. We developed 18 distinct ML models to predict the impact of non-coding variants on 39,437 cell-class-specific regulatory elements. These models demonstrate accuracy over 90% and a high degree of cell class specificity. Variant Impact Prediction (VIP) scores highlight specific sequences within candidate CREs, including putative transcription factor (TF) binding motifs, that are predicted to alter CRE function if mutated. Correlations to massively parallel reporter assays support the predictive value of VIP scores to model single nucleotide variants and indels in a cell-class-specific manner. These analyses demonstrate the capacity for single nucleus epigenomic data to predict the impact of non-coding sequence variants and allow for rapid prioritization of patient variants for further functional analysis.
Exploring Pain Researcher and Clinician Perceptions of Complementary, Alternative, and Integrative Medicine: A Large-Scale, International Cross-Sectional Survey
Authors: Ng Jeremy Y. , Anheyer Dennis , Cramer Holger
Published: February 2025

Background

Complementary, alternative, and integrative medicine (CAIM) is gaining popularity among patients experiencing pain, alongside traditional treatments. This study aimed to explore the views of pain clinicians and researchers on CAIM interventions.

Methods

An anonymous, online survey was distributed to 46 223 authors who had published pain-related research in MEDLINE-indexed journals. The survey included multiple-choice questions and open-ended sections to gather detailed opinions.

Results

A total of 1024 participants responded, most identifying as either pain researchers (43.59%) or both researchers and clinicians (39.88%). Many held senior positions (61.55%). Among the CAIM modalities, mind-body therapies such as meditation, yoga, and biofeedback were viewed as the most promising for pain prevention, treatment, and management, with 68.47% of participants endorsing these approaches. While a majority (43.89%) believed that most CAIM therapies are safe, only 25.55% expressed confidence in their effectiveness. There was broad agreement on the need for more research into CAIM therapies, with 45.88% agreeing and 42.53% strongly agreeing that further investigation is valuable.

Additionally, many respondents supported the inclusion of CAIM training in clinician education, either through formal programs (46.40%) or supplementary courses (52.71%). Mind-body therapies received the most positive feedback, while biofield therapies were met with the most skepticism.

Conclusion

These findings highlight the interest in CAIM among pain specialists and emphasize the need for more research and education tailored to this area.