bluuebunny/crossref_metadata_2025 huggingface dataset:
Long-term (12 months) vs. short-term (<12 months) dual antiplatelet therapy post-percutaneous coronary intervention with drug-eluting stents: a critical appraisal and systematic review
Authors: Abbott Kolten , Seton Nicholas , Kaur Gurjeevan , Zhao Jilai , Jones Mark , Singh Kuljit
Published: January 2025

Background

A growing body of evidence supports short-term DAPT as safe and efficacious following PCI with DES. However, methodological criticism of RCTs has led to caution when translating results into clinical practice. This study aimed to critically appraise the methodological rigour of included studies and consolidate the evidence on the safety and efficacy of short-term DAPT.

Methods

Medline, Cochrane Library and Embase were searched from inception until August 2022. The primary outcome was the methodological quality of published primary studies. Risk of bias was assessed using RoB 2.0 and the CASP tool. Evidence was rated for quality using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) score approach. Other endpoints were all-cause mortality and major bleeding.

Results

Eighteen RCTs were included. Based on GRADE score, there was a moderate level of certainty that the reported results for both outcomes are probably close to the true effect. A total of 78% (14/18) of RCTs had a low risk of bias when assessing all-cause mortality and 61% (11/18) when assessing major bleeding. The CASP tool confirmed methodological rigour; however, only 33% (6/18) of studies were applicable beyond the studied populations. Compared with 12 months of DAPT, short-term DAPT was associated with a reduced risk of major bleeding [relative risk (RR): 0.69, 95% CI: 0.54–0.88, P = 0.003, I
2 = 45%] and trended towards a reduced risk in all-cause mortality (RR: 0.90, 95% CI: 0.79–1.01, P = 0.08, I
2 = 0%).

Conclusion

With moderate certainty evidence, short-term DAPT appears safe and efficacious post-PCI with DES in the studied populations.
Association Between Average Daily Activity Counts and Knee Osteoarthritis Progression
Authors: Tang Xiaozhen , Li Dongze , Yao Haishan , Chen Xuanchen , Fan Liangquan , Hou Zhenhai
Published: January 2025

Objective

To explore the relationship between daily activity counts and knee osteoarthritis (OA) progression.

Design

A cohort study using Osteoarthritis Initiative (OAI) data included 610 participants aged 45-79 years with knee OA or at risk. Daily activity counts were measured using ActiGraph GT1M accelerometers. OA progression was assessed via Kellgren-Lawrence (KL) grade and joint space narrowing (JSN) scores over two years. Cox proportional hazard and Restricted Cubic Spline models identified the dose-response relationship and optimal activity threshold.

Results

The average age of participants was 63.7 years, with 44.8% male. A U-shaped relationship was observed between daily activity counts and OA progression. Moderate activity levels could be associated with a reduced risk of KL-grade (adjusted HR: 0.33; 95% CI: 0.24-0.44) and JSN-score progression (HR: 0.31; 95% CI: 0.25-0.38) for activity below 3263.3 counts/min. However, higher activity levels may increase KL-grade (HR: 1.57; 95% CI: 1.40-2.75) and JSN-score progression risk (HR: 1.27; 95% CI: 1.13-1.43).

Conclusion

Moderate activity may protect against knee OA progression, while low and high levels may increase risk. Tailored activity recommendations are needed for individuals with or at risk for OA. Future research should investigate the mechanisms and refine activity thresholds for OA management.
The True Appearance Behind Satisfaction in Young Women: A Study Using Stereophotogrammetry and FACE-Q
Authors: Andrade Lilian Mendes , Fernandes Anna Luísa Alves , Magri Laís Valencise , Mazzi-Chaves Jardel Francisco , de Vasconcelos Paulo Batista , Siéssere Selma , Regalo Simone Cecilio Hallak , Palinkas Marcelo
Published: January 2025

This cross-sectional observational study aimed to investigate the relationship between satisfaction with facial appearance among young women, as measured by the FACE-Q tool, and facial asymmetry quantified through stereophotogrammetry. A total of 50 women aged 18 to 30 years with a normal body mass index were recruited for the study. Participants were categorized as either symmetrical or asymmetrical based on facial asymmetry assessments obtained through clinical examination and stereophotogrammetry using the Vectra M3 system. Facial asymmetry was quantified using root mean square (RMS) distances, with participants classified into symmetrical (RMS ≤0.68) and asymmetrical (RMS >0.68) groups. The statistical analysis included the intraclass correlation coefficient (ICC) to assess the repeatability of RMS measurements (ICC=0.945), Receiver operating characteristic (ROC) curve analysis (area under the curve=0.900), and independent t tests to compare FACE-Q scores between groups. Results showed no significant differences in FACE-Q satisfaction scores between the symmetrical and asymmetrical groups. In addition, simple linear regression analysis indicated that RMS values were not predictive of FACE-Q scores, suggesting that facial asymmetry, as measured in this study, did not have a direct effect on self-reported satisfaction with appearance. These findings highlight the nuanced nature of individual satisfaction with facial appearance, suggesting that health care providers should combine clinical evaluation with empathetic communication to address both the aesthetic and functional concerns of patients more effectively.
Risk Factors and Treatment Strategies for Subcutaneous Effusion Secondary to Cerebrospinal Fluid Leakage After Craniotomy
Authors: Yuan Susu , Chen Yanlin , Jin Yichao , Jia Feng
Published: January 2025

Objective:

To confirm the incidence of subcutaneous effusion secondary to cerebrospinal fluid leakage after craniotomy, analyze the risk factors for cerebrospinal fluid leakage leading to subcutaneous effusion, summarize the underlying causes of its occurrence and explore the corresponding treatment strategies.

Methods:

A retrospective analysis was conducted on 757 patients who underwent craniotomy at our hospital from January to December 2023. The authors documented the sex, age, surgical characteristics, and history of chronic diseases for all patients, including those who developed subcutaneous effusion secondary to cerebrospinal fluid leakage. These factors were subjected to univariate regression analysis, and the identified risk factors were evaluated in a multivariate regression analysis.

Results:

Among 757 patients who underwent craniotomy, 15 developed subcutaneous effusion secondary to cerebrospinal fluid leakage, representing an incidence of 1.98%. This group included 5 patients with acoustic neuroma surgery, 4 with neurovascular decompression, 4 with meningioma surgery, 1 patient undergoing a posterior corpus callosotomy for epilepsy, and 1 patient with cerebellar cavernoma resection. Factors such as acoustic neuroma surgery, neurovascular decompression, infratentorial surgery, longer surgical durations, larger cranial bone removals, higher body mass index, and smoking were associated with an increased risk of developing subcutaneous effusion secondary to cerebrospinal fluid leakage. The average time to onset was 40.8 ± 37.16 days. Three patients with subcutaneous effusion experienced elevated body temperatures, with one testing positive in blood cultures; no other complications were noted. All patients initially received conservative treatment and subsequently underwent surgical repair for the cerebrospinal fluid leak an average of 45.4 ± 57.94 days later, ultimately resulting in recovery and discharge.

Conclusion:

In 2023, the incidence of subcutaneous effusion secondary to cerebrospinal fluid leakage after craniotomy at our hospital was 1.98%. The fundamental cause of this complication is the pressure difference between the inside and outside of the dura mater, leading to incomplete dural closure and subsequent fluid leakage. Factors such as younger age, acoustic neuroma surgery, neurovascular decompression, infratentorial surgery, longer surgery durations, larger cranial bone removals, higher body mass index, and smoking are associated with an increased risk of subcutaneous effusion. Once subcutaneous effusion occurs, conservative management is the initial step. To optimize outcomes, surgical repair of the cerebrospinal fluid leak should follow conservative treatment. This approach can significantly reduce the likelihood of treatment failure, decrease hospital stays, and cut unnecessary costs.
Where Are All the Clinical Trials for Chronic Rejection?
Authors: Cravedi Paolo , Maggiore Umberto , Molinari Paolo , Levitsky Josh , Zorn Emmanuel
Published: January 2025

Chronic rejection is arguably the main obstacle to long-term graft survival. Yet, clinical trials focusing on this condition are disappointingly scarce. Significant advances in treating chronic rejection cannot happen if there is no conduit for testing novel therapies. Here, we identified the main hurdles holding back clinical trials for chronic rejection and outlined a series of actions to address these roadblocks. We suggest that a new strategic plan combining expertise in basic and clinical research and leveraging complementary resources be launched to specifically target chronic rejection and achieve long-awaited progress. We only need the will.
The American Clinical Neurophysiology Society Guideline on Indications for Continuous Electroencephalography Monitoring in Neonates
Authors: Wusthoff Courtney J. , Numis Adam L. , Pressler Ronit M. , Chu Catherine J. , Massey Shavonne , Clancy Robert R. , Nguyen Sylvie , Hahn Cecil D. , Scher Mark S. , Pilon Betsy , King Donald T. , Wong Hong-nei , Tsuchida Tammy N. , Riviello James J. , Shellhaas Renée A.
Published: January 2025

Purpose:

Continuous EEG (cEEG) monitoring is increasingly used in the management of neonates with seizures. There remains debate on what clinically relevant information can be gained from cEEG in neonates with suspected seizures, at high risk for seizures, or with definite seizures, as well as the use of cEEG for prognosis in a variety of conditions. In this guideline, we address these questions using American Clinical Neurophysiology Society structured methodology for clinical guideline development.

Methods:

A working group was formed from American Clinical Neurophysiology Society membership with expertise in neonatal cEEG and a set of priority questions developed. We performed literature searches in PubMed and EMBASE to identify relevant studies. Evidence tables were compiled from extracted data and quality assessments performed. A modification of the GRADE process was used to evaluate the body of evidence and draft recommendations.

Results:

Our working group identified six priority questions to evaluate the accuracy of cEEG for neonatal seizure diagnosis and the formulation of prognosis. An initial literature search yielded 18,167 results, which were distilled to a set of 217 articles. Overall, the quality of evidence for most priority questions was rated as very low and we provided conditional recommendations based on published literature and expert consensus. For each priority question, we also considered the benefits and harms of cEEG, with relative harms considered to be far less than the potential benefits across recommendations.

Conclusions:

We present evidence-based clinical guidelines regarding indications for cEEG monitoring in neonates. Considering resource utilization and feasibility, when cEEG monitoring results have a likelihood of altering clinical decision making, the authors felt the resource investment was justifiable.
Chionosphaera pinicorticola sp. nov., a novel basidiomycetous yeast species isolated from pine tree bark in Gyeongju, South Korea
Authors: Lee Sangsu , Ahn Chorong , Kim Ye-Jin , Choi Seong-Min , Ko Jung-Woo , Kim Changmu , Park Cheon-Seok
Published: January 2025

A novel yeast species, isolated from the bark of pine trees in Gyeongju, South Korea, and designated as KCTC 37304T (ex-type KACC 410729), is characterized by its genetic, morphological and physiological properties. Molecular phylogenetic analysis involving the D1/D2 domain of the 26S LSU rRNA gene and the internal transcribed spacer (ITS) region confirms that it belongs to the genus Chionosphaera. In comparison to Chionosphaera cuniculicola CBS:10065, the type strain of its closest relative, KCTC 37304T exhibits 8 nucleotide substitutions (~2.07%) in the D1/D2 domain and 54 substitutions (~8.47%) in the ITS region. Morphologically, cells of KCTC 37304T are globose to ovoid, which distinguishes them from the cylindrical cells of C. cuniculicola. Physiologically, KCTC 37304T does not assimilate methanol or ethanol but can utilize succinate and xylitol, further differentiating it from C. cuniculicola. Based on these distinctive genetic, morphological and physiological features, we propose the new species Chionosphaera pinicorticola sp. nov., with KCTC 37304T (ex-type strain KACC 410729) designated as the holotype.
Ecological insights into the microbiology of food using metagenomics and its potential surveillance applications
Authors: Bloomfield Samuel J. , Hildebrand Falk , Zomer Aldert L. , Palau Raphaëlle , Mather Alison E.
Published: January 2025

A diverse array of micro-organisms can be found on food, including those that are pathogenic or resistant to antimicrobial drugs. Metagenomics involves extracting and sequencing the DNA of all micro-organisms on a sample, and here, we used a combination of culture and culture-independent approaches to investigate the microbial ecology of food to assess the potential application of metagenomics for the microbial surveillance of food. We cultured common foodborne pathogens and other organisms including Escherichia coli, Klebsiella/Raoultella spp., Salmonella spp. and Vibrio spp. from five different food commodities and compared their genomes to the microbial communities obtained by metagenomic sequencing following host (food) DNA depletion. The microbial populations of retail food were found to be predominated by psychrotrophic bacteria, driven by the cool temperatures in which the food products are stored. Pathogens accounted for a small percentage of the food metagenome compared to the psychrotrophic bacteria, and cultured pathogens were inconsistently identified in the metagenome data. The microbial composition of food varied amongst different commodities, and metagenomics was able to classify the taxonomic origin of 59% of antimicrobial resistance genes (ARGs) found on food to the genus level, but it was unclear what percentage of ARGs were associated with mobile genetic elements and thus transferable to other bacteria. Metagenomics may be used to survey the ARG burden, composition and carriage on foods to which consumers are exposed. However, food metagenomics, even after depleting host DNA, inconsistently identifies pathogens without enrichment or further bait capture.
Roles ofspoVFoperon subunits A and B in regulating cell morphology and biofilm formation in the biocontrol agentBacillus subtilis
Authors: Yang Yang , Zhou Yu-Xin , Jia Le-Yao , Song Xin-Yang , Lai Ya-Jie , Wang Su-Yan , Laborda Pedro , Shi Xin-Chi
Published: January 2025

Enhanced expression ofspoVFoperon (sporulation initiation factor; dipicolinic acid (DPA) synthase) inBacillus subtilisvegetative cells has been reported to increase host attachment and biocontrol ability. However, how thespoVFoperon regulates these essential biocontrol factors remains unknown. In this study, it was found that the knockout of thespoVFAorspoVFBsubunits, individually (ΔA andΔB), or together (ΔAΔB), decreased DPA biosynthesis, host attachment, nutrient competition ability, and biocontrol efficacy inB. subtilis. Moreover, the cell shape of the knockout strains changed from short rod to spherical. qRT-PCR analysis indicated that thespoVFoperon regulates TCA cycle expression and biofilm formation by balancing the amounts of various transcriptional factors, such as spo0A, SinR, and AbrB, and the cofactor NADPH. The regulatory mechanism of thespoVFoperon inB. subtilisbiofilm-related genes was proposed for the first time.

IMPORTANCE

Bacillus subtilis SpoVFoperon contains thespoVFAorspoVFBsubunits, which are responsible for the dipicolinic acid synthase activity. Dipicolinic acid is an important component ofB. subtilisspores. In this study, the roles ofspoVFAorspoVFBsubunits in the biocontrol abilityB. subtiliswere examined, indicating that thespoVFAsubunit plays a key role inB. subtilisbiofilm formation, cell morphology, growth, and nutrient competition ability. Additionally, the regulatory network connecting thespoVFoperon with biofilm formation-related genes ofB. subtiliswas proposed. The results obtained in this study help to understand key genes involved in the biocontrol ability ofB. subtilis.
Changes in Muscle Activation and Joint Motion During Walking After Transtibial Amputation with Sensory Feedback from Spinal Cord Stimulation: A Case Study
Authors: Bose Rohit , Petersen Bailey A , Sarma Devapratim , Barra Beatrice , Nanivadekar Ameya C , Madonna Tyler J , Liu Monica F , Levy Isaiah , Helm Eric R , Miele Vincent J , Fisher Lee E , Weber Douglas J , Dalrymple Ashley N
Published: January 2025

Background

The goal of this study was to examine the effects of spinal cord stimulation (SCS) on muscle activity during walking after lower-limb amputation. Amputation results in a loss of sensory feedback and alterations in gait biomechanics, including co-contractions of antagonist muscles about the knee and ankle, and reduced pelvic obliquity range-of-motion and pelvic drop. SCS can restore sensation in the missing limb, but its effects on muscle activation and gait biomechanics have not been studied in people with lower-limb amputation.

Methods

This case study included a participant with transtibial amputation who was implanted percutaneously with SCS electrodes over the lumbosacral enlargement for 84 days. SCS was used during in-lab experiments to provide somatosensory feedback from the missing limb, relaying a sense of plantar pressure when the prosthesis was in the stance phase of the gait cycle. We used electromyography (EMG) to record muscle activity from the residual and intact limbs, and 3D motion capture to measure pelvic obliquity. EMG signals were recorded during walking with and without SCS at early and late time points across the implant duration.

Results

During walking, co-contraction of knee antagonist muscles was reduced following multiple sessions of SCS-mediated sensory restoration. Additionally, the activation of the hip abductor (tensor fasciae latae) muscle increased activity during gait with SCS-mediated sensory restoration, which corresponded to an increase in pelvic obliquity range-of-motion and pelvic drop, towards normal.

Conclusions

Restoring sensation in the missing limb using SCS modulated muscle activity during walking leading to improved coordination and pelvic motion in an individual with lower-limb amputation.
PREVALENCE OF HCV AMONG HOUSEHOLD MEMBERS OF HEPATITIS C VIRUS-INFECTED PATIENTS ATTENDING CENTRE UNIVERSITAIRE DE SANTE PUBLIQUE (CUSP) HEALTH CENTER
Authors: Nemeyimana Patrick , Fabrice Uwumuremyi , anselme Ruhumuriza , Pierre Bakunzibake , Mugisha Emmy , Karenzi Valens , Shema Eliah , Kiiza Pascal
Published: January 2025

Globally, hepatitis C is included in the public health concern. More than 1.4 million deaths are reported. In 170 million who are infected with HCV worldwide,71 million have serious complications. There is a close relationship between hepatitis C infections among family members with one case. Family member’s behaviors and exposure to positive family members without precautions are among the risk factor of getting hepatitis C infection. In Rwanda, the burden of Hepatitis C infections reaches to 4% of infected people. High prevalence of hepatitis C infection can be associated with horizontal transmission among household of positive patients for HCV. In Rwanda no data showing the contribution of horizontal transmission of HCV among household members as one of the risk factors to increase the prevalence of HCV.

The objective of this study was to determine the prevalence of HCV among the household members living with HCV positive individual, specifically attending centre universitaire de santé public of BUTARE.

The study used a descriptive cross-sectional design to assess the prevalence among 30 families having had positive cases for HCV with 180 sample size. With use of questionnires, HCV risk factors were assessed from our participants and from their responses. Purposive sampling was done for HCV rapid test and positive cases sample were confirmed at university teaching hospital of BUTARE with Elisa.

From participants tested, 10.8% were tested positive for HCV counting for the prevalence of our study. Our findings are in line with other same studies conducted in Egypt and Iran revealed that there was 14.1%, which is a bit closer to our finding. we have found that unprotected sex with parnters and marital status between infected cases has a big influence to the high prevelence.

Based on the findings from our study, 10.8% of our participants tested positive for HCV due to limited education, awareness, and exposure to contributing risk factors about HCV transmission.
Systematic Prioritisation of AI-Detected Chest X-ray Abnormalities for Optimised Lung Cancer Detection
Authors: Bramley Rhidian , Sharman Anna , Duerden Rebecca , Lyon Sarah , Ryan Melissa , Weber Elodie , Brown Louise , Evison Matthew
Published: January 2025

Objective

This study aimed to establish a reproducible method for selecting AI-detected chest X-ray (CXR) abnormalities prioritised for urgent reporting to support faster lung cancer diagnosis. By selecting findings informed by cancer prevalence and clinical significance, we sought to maximise detection while maintaining a high negative predictive value (NPV).

Materials and Methods

Two cohorts of CXRs were evaluated: (1) a retrospective cohort of patients with confirmed lung cancer and abnormal CXRs, and (2) a prospective cohort of primary care referred CXRs from seven Greater Manchester trusts, with the AI system in shadow mode. The AI triage system (Annalise Enterprise CXR) evaluated the relative prevalence of 124 abnormalities, and prioritisation strategies were assessed using sensitivity, specificity, positive predictive value (PPV), and NPV.

Results

A total of 1,282 lung cancer patients were included in cohort 1. In cohort 2, the AI system processed 13,802 CXRs. Sensitivity was 95.87% (94.77%-96.97%) in cohort 1, and specificity was 79.11% (78.43%-79.79%) in cohort 2, with an NPV of 99.95%.

Conclusion

This study presents a systematic, reproducible method for prioritising AI-detected CXR abnormalities, balancing high sensitivity and NPV while minimising low-risk prioritisation. This approach provides a data-driven alternative to traditional methods relying solely on clinical judgement.
Association between LVEF-1 and Coronary Artery Stenosis and Interventional Treatment Efficacy
Authors: Tang Chao , Yan Bin , Xiong Li , Zhu Yanyu , Ren Jiaxing , Li Xiang , Gu Xiaosong
Published: January 2025

Background

Myocardial ischemia leads to a decrease in the speed and intensity of myocardial tissue contraction. In the early stages, this cardiac dysfunction is difficult to be detected by conventional echocardiography methods.

Objective

First-phase left ventricular ejection fraction (LVEF-1) serves as a sensitive indicator for evaluating myocardial contractility. The aim of this study was to assess the decreased cardiac function caused by myocardial ischemia and its improvement following interventional treatment, as measured by LVEF-1.

Methods

207 patients were enrolled. Based on the results of the angiography, they were categorized into three groups: mild, moderate, and severe. The LVEF-1, Gensini score and other clinical data were compared among these groups. Furthermore, logistic regression analysis was used to analyze the relationship between LVEF-1 and coronary artery stenosis, as well as factors associated with improvement in LVEF-1 following interventional treatment using linear regression.

Results

The LVEF-1 of patients in the 3 groups were 29.6 (28.2, 31.7) %, 27.8 (27.0, 28.6) %, and 25.2 (23.6, 26.5) % (p<0.001). There was a negative relationship between LVEF-1 and the Gensini score (r=-0.694, p<0.001), as well as between LVEF-1 and BNP (r=-0.244, p<0.001). LVEF-1 was identified as an independent predictor for coronary artery stenosis ≥50% or ≥70%. A cutoff value of 26.9% for LVEF-1 had a sensitivity of 89.5% and specificity of 83.9% for predicting the coronary artery stenosis ≥70%. Following intervention, LVEF-1 increased from 24.70 (23.30, 26.32) % to 28.10 (26.80, 29.92) % in 82 patients. Stent diameter was identified as an independent factor influencing the improvement in LVEF-1 post-intervention.

Conclusions

LVEF-1 is negatively correlated with the severity of coronary artery stenosis, and it increases after receiving coronary artery intervention therapy, suggesting that LVEF-1 can serve as a new indicator to evaluate the severity of coronary artery stenosis and the efficacy of interventional treatment.
Applicability of a short form of the Speech, Spatial and Qualities of Hearing Scale in 97 individuals with Menière’s disease in a multicenter registry
Authors: Spiegel Jennifer L. , Lehnert Bernhard , Schuller Laura , Adler Irina , Rader Tobias , Brzoska Tina , Weiss Bernhard G. , Canis Martin , Busch Chia-Jung , Ihler Friedrich
Published: January 2025

BACKGROUND

Menière’s Disease (MD) is a debilitating disorder with episodic and variable ear symptoms. Diagnosis can be challenging and evidence for a psychometric instrument to assess subjective impairment of hearing and the associated burden in daily life is currently lacking.

OBJECTIVE

To evaluate a short form of the Speech, Spatial and Qualities of Hearing Scale (SSQ) for hearing-related disability in MD.

METHODS

Data was collected from a multicenter prospective patient registry for long-term follow up of MD patients. Hearing was assessed by pure tone and speech audiometry. The SSQ was applied in a version with 17 items.

RESULTS

97 consecutive patients with unilateral MD had a mean age of 56.2 ± 5.0 years. 55 individuals (57.3%) were female, 72 (75.0%) were categorized as definite MD. Average total score of the SSQ was 6.0 ± 2.1. Cronbach’s alpha for internal consistency was 0.960 for the total score. We did not observe undue floor or ceiling effects. SSQ values showed a negative correlation with hearing thresholds and a positive correlation with speech recognition scores.

CONCLUSIONS

The short form of the SSQ provides insight into hearing-specific disability in patients with MD. Thereby, it may be informative regarding disease stage and rehabilitation needs.
Investigating the genetic relationship between vitamin B12 deficiency and Parkinson’s disease
Authors: Dering Raphael , Onvumere Margarita , Liu Lang , Huot Philippe , Gan-Or Ziv , Senkevich Konstantin
Published: January 2025

Introduction

Epidemiological studies suggest that patients with Parkinson’s disease (PD) may have lower levels of vitamin B12 compared to healthy controls, and it was proposed that PD patients could benefit from vitamin B12 supplementation. Functional studies have shown that B12 could modify LRRK2 activity and may directly interact with alpha-synuclein. This study aimed to investigate the role of common and rare variants in genes related to B12 metabolism and assess the potential causal relationships between B12 levels and PD risk, age-at-onset, and motor/cognitive progression.

Methods

We investigated the association between common and rare variants in genes involved in vitamin B12 metabolism. Rare variants (minor allele frequency < 0.01) were analyzed using the optimal sequence kernel association test (SKAT-O) in 4,815 PD patients and 65,607 controls from two independent cohorts. We constructed pathway-specific polygenic risk scores (PRS) for genes essential to B12 metabolism and for genes identified in previous genome-wide association studies (GWAS) on B12 metabolism. Mendelian randomization and genetic correlation analyses were applied to explore the relationship between vitamin B12 levels and PD risk, age-at-onset, and disease progression.

Results

Our analysis showed no associations between common variants of genes crucial in B12 metabolism and PD. Pathway PRS identified nominal association between B12-related genes and PD (OR = 1.061, 95% CI: 1.004–1.121, p = 0.038), which did not survive Bonferroni correction. In the rare variants analysis, we identified a significant association between variants with high CADD scores in theCUBNgene (P=6.07E-05; Pfdr=0.005) in the AMP-PD cohort, driven by the benign variant p.G3114S (OR=3.3; p=3.56E-05); however, this was not validated in the meta-analysis. We did not identify a potentially causal relationship between vitamin B12 levels and the risk, age-at-onset, or progression of PD. Additionally, no genetic correlation was observed between vitamin B12 and PD risk or age-at-onset GWASs.

Conclusion

Overall, our analyses indicate lack of genetic link between B12 levels or metabolism and PD.
LUKB DT: A Web Tool for Quick and Efficient Identification of Disease Trajectories
Authors: Li Xiangnan , Zhang Hui , Jiang Shuai , Gao Baocai , Hu Zixin
Published: January 2025

As the volume of electronic medical data grows, understanding disease progression and identifying risk factors have become central to public health research. Disease trajectories provide valuable insights into disease progression and risk factors. LUKB DT (LUKB Disease Trajectories) is a user-friendly web tool designed to facilitate disease trajectory analysis using electronic medical records (EMR), particularly the UK Biobank data. LUKB DT processes EMR data, including patient ID, disease diagnoses, corresponding timestamps, and other relevant variables, combining Cox regression, binomial tests, and conditional logistic regression to identify disease trajectories. This tool offers a quick and efficient way to prepare and analyze disease trajectories, contributing to the expanding field of disease trajectory research and providing valuable insights for risk factor identification and disease progression studies. Detailed deployment and usage can be found in the Supplementary Material.

LUKB DT is freely available athttps://github.com/HaiGenBuShang/LUKB.
Approaches for measuring socioeconomic status in health studies in Sub-Saharan Africa: a scoping review
Authors: Yopa Daniele Sandra , Kiki Gbetogo Maxime , Ngangue Patrice , Ngoufack Marie Nicole , Lekelem Dongmo Gilles Protais , Mbang Massom Douglas , Amvella Priscillia Anya , Bongwong Tamfon Brian , Chichom-Mefire Alain , Juillard Catherine , Hubbard Alan , Nguefack-Tsague Georges
Published: January 2025

Background

Socioeconomic status (SES) is essential for determining a person or community’s position about certain social and economic characteristics. This is particularly important in sub-Saharan Africa, where health disparities are pronounced. We conducted a scoping review to explore approaches used in health studies to measure socio-economic status in the sub-Saharan region.

Methods

A comprehensive literature search covering January 2012 to June 2024 was conducted in five databases: PubMed, EMBASE, CIHNAL, Web of Science, and African Index Medicus. All studies in sub-Saharan Africa focused on health-related socioeconomic status were included, regardless of study methodology. Three peer reviewers independently evaluated the selected articles according to inclusion and exclusion criteria. Discrepancies between reviewers were resolved through a consensus meeting. The review protocol was registered on the Open Science Framework (OSF,OSF.IO/7NGX3).

Results

The initial search yielded 19,669 articles. At the end of the screening process, 65 articles were analysed. Cross-sectional studies have been widely used. South Africa (13.4%) and Kenya (11%) were the most represented countries. Maternal, neonatal, and infant/juvenile health was the most covered theme (31%). The review identified 12 categories of SES measurement methods, with the asset-based wealth index being the most widespread (61.9%). Principal component analysis (PCA) is the primary analytical method used to calculate this index (57.7%).

Conclusions

This scoping review identified the asset-based wealth index as the most frequently used and provided essential elements for pooling different SES calculation methodologies to reach a consensus. Using SES to improve interventions is important to limit African health disparities.
PERFORMANCE OF FOUR NEWLY RELEASED CASSAVA VARIETIES IN A FALLOWED LAND OVER TWO FARMING SEASONS
Authors: Ossai C. O. , Ojobor S. A. , Ogwuche T. O. , Akpeji S. C. , Alama I. S. , Diebiru-Ojo E. M.
Published: January 2025

Cassava (Manihot esculentaCrantz) is an important crop for humans due to its staple and industrial values. Currently the demand is more than the supply as the current output falls below the expected. This necessitated the breeding of superior genotypes that are high yielding. These superior genotypes also requires a fertile soil for optimum production. However, this has been primarily achieved through the application of inorganic manures. It is then important to evaluate four newly released cassava varieties in an organically enriched soil relative to the local best variety. Four newly released cassava varieties, Hope, Obasanjo2, Baba 70, and Game changer, and one Local Best (LB) was planted in 5-years fallowed farm lands at three plots (A, B and C) for 2 seasons. It was a three-way factorial (5-varieties*3-farms*2-seasons) arranged in a randomized complete block design and replicated three times. Data were taken on the Fresh Tuber Weight (FTW) and Stem Height (SH) per variety, and pre and post soil status. Data were analyzed using analysis of variance, while differences in varietal means were separated using least significant differences at 5% level of significance. The FTW and SH differed significantly across varieties, years and interaction between variety, farms and year, and ranged from 19.2±0.5 (LB) to 41.0±0.5 (Obasanjo2), 32.1±0.4 (farm C) to 34.1±0.4 (farm A), 30.4±0.3 (year two) to 35.0±0.3 (year one), and the interactions between variety and year, farms and year, and variety, year and farms were significant. The soil macro and micro elements declined in the post relative to the pre status. The yield obtained from the improved varieties almost doubled the local best and yield declined in the second season.
A Multidisciplinary Theoretical Framework for Enhancing Scientific Writing: A Validated Model for Supporting Young Researchers
Authors: Köpeczi-Bócz Tamás
Published: January 2025

This study investigates multidisciplinary innovation in the teaching of scientific writing, focusing on the development of a theoretical framework and its experimental validation. The framework integrates logical thinking, creativity, and adaptability to enhance scientific writing skills and communication competencies. The experiment involved a four-semester university program guiding students from creative writing to complex scientific article production within diverse multidisciplinary contexts. The proposed methodology is also applicable in research institutions, corporate training programs, and other roles requiring proficiency in multidisciplinary scientific writing.

The findings demonstrate that the framework significantly improved students’ reasoning, structured thinking, and innovation capabilities, enabling them to present novel ideas effectively in academic settings. A key outcome of the program was the advancement of metacognitive awareness, supported by AI tools, allowing students to critically evaluate and refine their work. Additionally, the study highlighted the role of AI in enhancing the structural and stylistic quality of scientific writing while addressing ethical considerations.

The sequential design of the methodology and the multidisciplinary environment fostered knowledge exchange among students from various disciplines, preserving the unique attributes of each field. The five-step analysis framework, used to compare the outcomes of experimental and control groups, revealed statistically significant advantages for students participating in the methodological program. This research underscores the importance of multidisciplinary approaches for advancing 21st-century scientific literacy and emphasizes the global adaptability of such innovative programs.
High-quality genome assemblies of 152 root commensal bacteria from the model legumeLotus japonicus
Authors: Gómez-Repollés Adrián , Villa-Rodriguez Eber , Ferguson Shaun , Radutoiu Simona
Published: January 2025

Bacterial culture collections represent a valuable tool for mechanistic understanding of microbiome assemblies and are increasingly used to assemble tailored synthetic communities to characterize their microbe-microbe interactions and those with the environment. Given the size of these collections, short-read sequencing is primarily used to capture the encoded genetic information. Whilst sufficient for many microbiome studies, this approach is not amenable for understanding bacterial genome evolution or detailed genetic analyses at the entire genome level. Here we report the assembly of 152 full bacterial genomes from theLj-SPHERE, theLotus japonicuscollection of root commensals. We performed long-read sequencing using Oxford Nanopore technology and used this together with pre-existing Illumina sequences tode novoassemble these into high quality genomes with improved contiguity and quality. These genomes now provide a solid platform for detailed, mechanistic understanding of microbiome assembly, dynamics and evolution in plants.
Chloroplast genome editing of Rubisco boosts photosynthesis and plant growth
Authors: Yamori Wataru , Nakazato Issei , Yuchen Qu , Sanga Yukina , Miyata Tomoko , Uehara Ryo , Noto Yuma , Namba Keiichi , Fukayama Hiroshi , Matsumura Hiroyoshi , Arimura Shin-ichi
Published: January 2025

Photosynthetic inefficiencies limit the productivity and sustainability of crop production and the resilience of agriculture to future societal and environmental challenges. Ribulose-1,5-bisphosphate carboxylase/oxygenase (Rubisco) has inherently low catalytic efficiency, making it a key target for photosynthesis and crop improvement. However, introducing mutations to the chloroplast-encoded Rubisco large subunit (rbcL), which contains the enzyme’s catalytic sites, is technically challenging. In this study, we successfully generated a range of chloroplast-genome-editedArabidopsis thalianaplants targetingrbcLby a targeted base editor, ptpTALECD. The M309I and D397N substitutions inrbcLresulted in an increased Rubisco catalytic rate (kcat) without any reductions of Rubisco content, thereby enhancing photosynthetic rates and plant growth under both current atmospheric CO2concentrations (i.e., 381 μmol mol−1) and projected future concentrations (i.e., 549 μmol mol−1). Cryo-electron microscopy (cryo-EM) structural analysis showed that the M309I and D397N substitutions, although located far from the catalytic site, induce structural alterations in the catalytic (60s) loops. Our findings highlight the potential of Rubisco engineering to improve plant photosynthesis and growth, and underscore the unique opportunities that chloroplast genome editing offers for enhancing photosynthesis and crop productivity and reducing atmospheric CO2levels in a non-GMO context.
Role of Cockayne Syndrome B (CSB) Protein in Genome Maintenance in Human Cells under Oxidative Stress
Authors: Low Grace Kah Mun , Ng Gavin Yong-Quan , Zeegers Dimphy , Ting Aloysius , Gopalakrishnan Kalpana , Khaw Aik Kia , Jayapal Manikandan , Hande M Prakash
Published: January 2025

Cockayne Syndrome (CS), a disorder marked by premature ageing and neurodevelopmental abnormalities, is primarily caused by mutations in the CSB protein, a critical component of the transcription-coupled repair pathway of nucleotide excision repair. This study explores the role of CSB in managing oxidative DNA damage and maintaining telomere integrity under oxidative stress conditions. We subjected CSB-deficient human fibroblasts (CS-B) and control fibroblasts to acute and chronic oxidative stress through hydrogen peroxide (H₂O₂) treatment and elevated oxygen levels. Our findings reveal that CS-B fibroblasts exhibit a distinct resistance to acute oxidative stress, as evidenced by their sustained viability and minimal cell cycle arrest compared to control fibroblasts. However, chronic oxidative conditions led to accelerated senescence in CS-B fibroblasts, demonstrated by increased telomere attrition rates, senescent morphology, and upregulated senescence-associated β-galactosidase activity. Further, gene expression analysis post-H₂O₂ exposure identified the downregulation of key DNA repair and cell cycle genes in CS-B fibroblasts, suggesting a compromised ability to respond to oxidative DNA damage. These observations underscore the multifaceted role of CSB in genomic maintenance and highlight its potential involvement in the pathology of CS through impaired response to oxidative stress and telomere instability. The study contributes to a deeper understanding of the cellular mechanisms that underlie CS symptoms and may inform potential therapeutic strategies targeting oxidative damage repair systems.
Searching for Sequence Features that Control DNA Cyclizability
Authors: Gordiychuk Margarita , Park Jonghan , Basu Aakash , Ha Taekjip , Bialek William , Zhang Yaojun
Published: January 2025

The mechanical properties of DNA molecules are crucial in many biological processes, from DNA packaging to transcription regulation. While the mechanics of long DNA typically follow the worm-like chain polymer model, multiple studies have shown that the mechanics of short DNA – at the length scale of DNA-protein interactions – depend strongly on its sequence content. Motivated by recent high-throughput measurements of sequence-dependent DNA cyclizability – the DNA’s tendency to mechanically bend and form a loop, we developed a statistical mechanics approach to systematically explore how cyclizability depends on interactions between individual nucleotides in the sequence. By applying this method to datasets of randomly generated and biologically derived sequences, we identified characteristic sequence features that control DNA cyclizability and extracted the most and least cyclizable sequences, the behavior of which we validated through all-atom molecular dynamics simulations. We found that while highly cyclizable sequences share the same periodic features across datasets, distinct sequence patterns can result in low cyclizability. This work contributes to our understanding of the sequence dependence of DNA mechanics and its role in various biological processes, and has implications for the growing field of DNA nanofabrication.
Brain Infiltrated Monocyte-Macrophages in a rat model of Temporal Lobe Epilepsy: Revisiting the Pro-Inflammatory Paradigm
Authors: Grabon Wanda , Gasmi Nadia , Lang Anatole , Ruiz Anne , Georges Béatrice , Blot Victor , Ogier Michaël , Rheims Sylvain , Navarro Fabrice P , Bezin Laurent
Published: January 2025

Neuroinflammation is central to temporal lobe epilepsy, yet the specific role of myeloid cells remains unclear. In status epilepticus (SE) models, circulating monocytes have been reported to infiltrate the brain, though distinguishing them from microglia remains challenging. Using a rat model, we traced infiltrating monocytes post-SE, to investigate their persistence, phenotypic evolution during epileptogenesis and contribution to neuroinflammation. By tracking phagocyted fluorescent nanoparticles and using CD68 immunohistochemistry, we confirmed that monocytes entered the brain in significant numbers 24 hours post-SE, after the inflammatory peak occurred (7h post-SE). Tracked up to 7 weeks, these cells adopted a microglia-like phenotype, contributed to the microglial scar and sustained low-grade inflammation during the chronic phase of epilepsy solely through their presence, as their expression of pro-inflammatory markers resembled that of non-activated microglia. Importantly, monocytes initially and transiently supported an anti-inflammatory response providing a unique opportunity to modulate neuroinflammation and potentially disrupt epilepsy progression, opening new avenues for therapeutic interventions.
Localized Reconstruction of Multimodal Distance Distribution from DEER Data of Biopolymers
Authors: Tsay Karen , Keller Timothy , Fichou Yann , Freed Jack H. , Han Song-I , Srivastava Madhur
Published: January 2025

Pulsed Dipolar ESR Spectroscopy (PDS) is a uniquely powerful technique to characterize the structural property of intrinsically disordered proteins (IDPs) and polymers and the conformational evolution of IDPs and polymers, e.g. during assembly, by offering the probability distribution of segment end-to-end distances. However, it is challenging to determine distance distributionP(r) of IDPs by PDS because of the uncertain and broad shape information that is intrinsic to the distance distribution of IDPs. We demonstrate here that the Srivastava-Freed Singular Value Decomposition (SF-SVD) point-wise mathematical inversion method along with wavelet denoising (WavPDS) can aid in obtaining reliable shapes for the distance distribution,P(r), for IDPs. We show that broad regions ofP(r) as well as mixed narrow and broad features within the captured distance distribution range can be effectively resolved and differentiated withouta prioriknowledge. The advantage of SF-SVD and WavPDS is that the methods are transparent, requiring no adjustable parameters, the processing of the magnitude for the probability distribution is performed separately for each distance increment, and the outcome of the analysis is independent of the user’s judgement. We demonstrate the performance and present the application of WavPDS and SF-SVD on model ruler molecules, model polyethylene glycol polymers with end-to-end spin labeling, and IDPs with pairwise labeling spanning different segments of the protein tau to generate the transparent solutions to theP(r)’s including their uncertainties and error analysis.
Sex-specific Associations of Gene Expression with Alzheimer’s Disease Neuropathology and Ante-mortem Cognitive Performance
Authors: Seto Mabel , Clifton Michelle , Gomez Melisa Lara , Coughlan Gillian , Gifford Katherine A. , Jefferson Angela L. , De Jager Philip L. , Bennett David A , Wang Yanling , Barnes Lisa L. , Schneider Julie A , Hohman Timothy J. , Buckley Rachel F. , Dumitrescu Logan
Published: January 2025

The biological mechanisms underlying women’s increased Alzheimer’s disease (AD) prevalence remain undefined. Previous case/control studies have identified sex-biased molecular pathways, but sex-specific relationships between gene expression and AD endophenotypes, particularly sex chromosomes, are underexplored. With bulk transcriptomic data across 3 brain regions from 767 decedents, we investigated sex-specific associations between gene expression and post-mortem β-amyloid and tau as well as antemortem longitudinal cognition. Of 23,118 significant gene associations, 10% were significant in one sex and not the other (sex-specific). Most sex-specific gene associations were identified in females (73%) and associated with tau tangles and longitudinal cognition (90%). Four X-linked genes,MCF2,HDAC8,FTX, andSLC10A3, demonstrated significant sex differences in their associations with AD endophenotypes (i.e., significantsex x geneinteraction). Our results also uncovered sex-specific biological pathways, including a female-specific role of neuroinflammation and neuronal development, reinforcing the potential for sex-aware analyses to enhance precision medicine approaches in AD.