bluuebunny/crossref_metadata_2025 huggingface dataset:
Single-cell mitophagy patterns within the tumor microenvironment modulate intercellular communication, impacting the progression and prognosis of hepatocellular carcinoma
Authors: Li Zhengyan , Chen Wei , Yao Shu , Peng Zuxiang , Liu Hongming , Tang Yongliang , Feng Yi
Published: January 2025

Background

Hepatocellular carcinoma (HCC) is a common malignant tumor of the digestive system with a high incidence that seriously threatens patients’ lives and health. However, with the rise and application of new treatments, such as immunotherapy, there are still some restrictions in the treatment and diagnosis of HCC, and the therapeutic effects on patients are not ideal.

Methods

Two single-cell RNA sequencing (scRNA-seq) datasets from HCC patients, encompassing 25,189 cells, were analyzed in the study. We utilized non-negative matrix factorization (NMF) clustering to identify mitophagy patterns in HCC TME cells, including cancer-associated fibroblasts (CAFs), T cells, B cells, and tumor-associated macrophages (TAMs). Cell-to-cell communication was analyzed using the CellChat package, and pseudotime trajectory analysis was performed using the Monocle package. Gene regulatory networks were investigated with the SCENIC package, and survival analyses were conducted with mitophagy-related signatures.

Results

HCC samples analysis identified 22 clusters, including 7 principal cell types. Complex cell communications were observed among these cell types. Mitophagy-related CAFs, TAMs, CD8+ T cells, and B cells were identified. These subtypes had different biological states, cell-cell communications, and metabolic pathways. Mitophagy levels were elevated in tumor samples. Changes in mitophagy-related genes within specific cell subtypes were associated with different overall survival rates. However, mitophagy did not seem to affect the effectiveness of immunotherapy.

Conclusion

This study provides evidence that mitophagy within the HCC TME modulates intercellular communication, influencing tumor progression and patient prognosis. Targeting mitophagy may offer a promising approach to improve the long-term prognosis of HCC patients.
Exploring post-rehabilitation plasticity with intra-cerebral recordings on anomic profiles
Authors: Trébuchon Agnès , Fasola Alexia , Sabadell Véronique , Dubarry Anne-Sophie , Carron Romain , Bartolomei Fabrice , Alario F.-Xavier
Published: January 2025

Background

Patients with drug-resistant epilepsy involving the language network often exhibit anomic profiles in daily life due to difficulties with lexical selection processes. Very little evidence is available regarding the effects of language rehabilitation in this population.

Objective(s)

We aim to induce brain plasticity combined with improvements in behavioral performance using language therapy in patients with epilepsy.

Methods

We implemented a therapy focused on phonological and semantic features of infrequent words over three treatment sessions, each targeting a specific semantic category. Intracranial signals were recorded in 10 patients during baseline and post-therapy picture-naming sessions. Response times and the percentages of correct responses during naming tests were collected. Time-frequency analyses were conducted on intracranial signals, and comparisons were made between baseline and post-therapy conditions for each patient.

Results

Half of the patients demonstrated improved naming skills following the treatment. We observed significantly different recruitment of frontotemporal areas in the left hemisphere (including Broca's area) post-therapy in patients that improved naming skills. Specifically, we found significantly different high-gamma activity in the posterior left inferior frontal gyrus 500 ms after stimulus onset in patients with improved naming skills vs. non-improved naming skills. This effect was not observed in the right hemisphere.

Conclusions

These findings suggest that enhanced performance following language therapy is associated with modifications in posterior left IFG activations during latencies closely tied to the lexical selection process.
Harnessing marine bacteria for next-gen antibiotics: potent inhibition of S. aureus and Riemerella anatipestifer through in vitro, omics, and chemoinformatics approach with enhanced production of secondary metabolites through zinc sulfate
Authors: Hassan Syed Shams ul , Jin Huizi
Published: January 2025

The rise of bacterial infections and increasing antibiotic resistance underscores an urgent need for new, effective antimicrobial agents with marine bacteria offering a unique and promising source for novel antibiotic compounds to combat persistent and emerging pathogens. In this research, five compounds were achieved from marine Streptomyces sp., C2-13, and their yield was enhanced with the addition of zinc sulfate at 0.5 mM. All compounds have been evaluated for their antibacterial activity against multiple pathogens, among which good activity was achieved against S. aureus, while potent activity was achieved against Riemerella anatipestifer with its IC50 value at 200 µm and bactericidal effect at 300 µm. Among all compounds, 4 was more active against both pathogens. A transcriptome analysis of active compound 4 showed its antibacterial effect on R. anatipestifer by inhibiting 30S and 50S ribosomal subunits, resistance mechanisms, and gliding motility proteins IX secretion system (T9SS) and interfering with protein translations process, secretion system, defense and resistance mechanisms, ultimately resulting in effective inhibition of normal bacterial growth and its motility. To investigate the anti-bacterial mechanism, all compounds were docked with two enzymes and TLR4 protein for predicting the vaccine construct, and the best docking score was achieved against RMFP with the highest score of -12.9 for compound 4. In silico cloning was carried out to ensure the expression of proteins generated and were cloned using E. coli as a host. The simulation studies have shown that both compound 4–RMFP and TLR4–RMFP complex are stable with the system. To the best of our knowledge, this is the first study investigating marine bacterial metabolites against R. anatipestifer with their anti-bacterial mechanism and enhancing their yield through the addition of zinc sulfate ions.
The association between the neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, and lymphocyte-to-monocyte ratio and delirium in ischemic stroke patients
Authors: Wang Pangbo , Huang Jing , Xu Liwei , Hu Rong
Published: January 2025

Background

Delirium is a severe neuropsychiatric symptom following acute ischemic stroke (IS) and is associated with poor outcomes. Systemic inflammation and immune dysregulation are believed to contribute to the pathophysiology of delirium. The neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and lymphocyte-to-monocyte ratio (LMR) are widely recognized as convenient and reliable biomarkers of systemic inflammation. However, their association with delirium after IS remains unclear.

Methods

In this study, we identified IS patients requiring ICU admission from the Medical Information Mart for Intensive Care (MIMIC)-IV database. We employed multivariable logistic regression and restricted cubic splines (RCS) to assess the association between the NLR, PLR, and LMR and delirium. Two-sample Mendelian randomization (MR) analysis was performed to further explore their causal relationship at the genetic level.

Results

A total of 1,436 patients with IS were included in this study, of whom 214 (14.9%) had delirium. In the multivariate logistic regression analysis, after adjustment for confounders, the patients in the highest quartile of the NLR (odds ratio [OR] 2.080, 95% confidence interval [CI], 1.282–3.375) and LMR (OR 0.503, 95% CI 0.317–0.798) and the patients in the second quartile of the PLR (OR 1.574, 95% CI 1.019–2.431) were significantly associated with delirium. The RCS function showed a progressive increase in the risk of delirium with higher NLR and PLR and lower LMR. In the MR analysis, only the PLR was negatively associated with the risk of delirium.

Conclusion

The observational studies found significant associations between the NLR, PLR, and LMR and delirium. However, the MR analysis only demonstrated a potential protective causal relationship between the PLR and delirium. Further prospective studies are needed to validate their association and to elucidate the underlying mechanisms.
Evaluation of the diagnostic efficiency of fluorescence in situ hybridization for pulmonary tuberculosis: a systematic review and meta-analysis
Authors: Hu Yu-Qi , Liu Kang , Lai Le-Qing , He Yi-Ru , Hong Li-Ping , Jiang Chu-Qian , Liu Si-Min , Cao Ming-Zhu
Published: January 2025

Objective

In clinical practice, an accurate and efficient detection approach for pulmonary tuberculosis (PTB) is highly needed. The fluorescence in situ hybridization (FISH) assay for PTB might be a suitable alternative to current tests. However, a systematic assessment of the diagnostic performance of this new approach is not available. Our study aimed to determine the diagnostic accuracy of FISH for PTB.

Methods

We examined PubMed and three more databases including Embase, Cochrane Library, and Web of Science databases from their establishment to November 10, 2023, for published articles on the diagnostic performance of FISH on individuals with clinical suspicion of tuberculosis (TB). QUADAS-2 was used to evaluate the literature’s quality. We used Meta-DiSc software to create forest plots.

Results

The search yielded 7 studies, involving 1,224 sputum samples that could be included in our meta-analysis. The combined FISH sensitivity and specificity were 0.89 (95% CI 0.86–0.92) and 0.98 (95% CI 0.97–0.99), respectively. Furthermore, subgroup analysis was performed based on probes and PTB incidence.

Conclusion

FISH may be useful in the diagnosis of pulmonary tuberculosis. The sensitivity and specificity of FISH are high for most sputum specimens. Additionally, FISH has better diagnostic performance in countries with low PTB prevalence than in high PTB prevalence countries. We hope this study will find a new and effective tool for the early diagnosis of PTB.
Individualized treatment recommendations for patients with locally advanced head and neck squamous cell carcinoma utilizing deep learning
Authors: Zhang Linmei , Zhu Enzhao , Shi Jiaying , Wu Xiao , Cao Shaokang , Huang Sining , Ai Zisheng , Su Jiansheng
Published: January 2025

Background

The conventional treatment for locally advanced head and neck squamous cell carcinoma (LA-HNSCC) is surgery; however, the efficacy of definitive chemoradiotherapy (CRT) remains controversial.

Objective

This study aimed to evaluate the ability of deep learning (DL) models to identify patients with LA-HNSCC who can achieve organ preservation through definitive CRT and provide individualized adjuvant treatment recommendations for patients who are better suited for surgery.

Methods

Five models were developed for treatment recommendations. Their performance was assessed by comparing the difference in overall survival rates between patients whose actual treatments aligned with the model recommendations and those whose treatments did not. Inverse probability treatment weighting (IPTW) was employed to reduce bias. The effect of the characteristics on treatment plan selection was quantified through causal inference.

Results

A total of 7,376 patients with LA-HNSCC were enrolled. Balanced Individual Treatment Effect for Survival data (BITES) demonstrated superior performance in both the CRT recommendation (IPTW-adjusted hazard ratio (HR): 0.84, 95% confidence interval (CI), 0.72–0.98) and the adjuvant therapy recommendation (IPTW-adjusted HR: 0.77, 95% CI, 0.61–0.85), outperforming other models and the National Comprehensive Cancer Network guidelines (IPTW-adjusted HR: 0.87, 95% CI, 0.73–0.96).

Conclusion

BITES can identify the most suitable treatment option for an individual patient from the three most common treatment options. DL models facilitate the establishment of a valid and reliable treatment recommendation system supported by quantitative evidence.
Case report: Electrical impedance tomography-guided ventilator weaning in an obese patient with severe pneumonia
Authors: Liu Yuxia , Liu Rui , Li Bin , Cai Libi , Hou Jieqi , Zhao Wei
Published: January 2025

Background

Electrical impedance tomography (EIT) evaluates lung function by providing continuous, real-time monitoring of regional lung ventilation distribution to guide the restoration of lung ventilation. Patients with obesity who are dependent on mechanical ventilation often struggle with weaning. This case report highlights the potential of EIT to guide the weaning of ventilator-dependent patients in an obese patient with severe pneumonia.

Case summary

A 23-year-old male obese patient was admitted to Zhongshan People’s Hospital in November 2023 due to progressive dyspnea. He suffered from recurrent fever and worsening oxygenation and had a 20+ year history of syringomyelia. Combined with abnormal computed tomography imaging, the discovery of a viral infection in the bronchoalveolar lavage fluid, and next-generation sequencing results, he was diagnosed with severe pneumonia. In addition to conventional treatment, EIT was used to guide him through postural changes and ventilation recovery. EIT-informed prone positioning improved ventilation distribution and facilitated successful ventilator weaning on day 26. The patient was discharged after recovering spontaneous respiratory function.

Conclusion

EIT may help ventilator-dependent obese patients achieve tailored targets to improve ventilatory outcomes.
Harnessing artificial intelligence in sepsis care: advances in early detection, personalized treatment, and real-time monitoring
Authors: Li Fang , Wang Shengguo , Gao Zhi , Qing Maofeng , Pan Shan , Liu Yingying , Hu Chengchen
Published: January 2025

Sepsis remains a leading cause of morbidity and mortality worldwide due to its rapid progression and heterogeneous nature. This review explores the potential of Artificial Intelligence (AI) to transform sepsis management, from early detection to personalized treatment and real-time monitoring. AI, particularly through machine learning (ML) techniques such as random forest models and deep learning algorithms, has shown promise in analyzing electronic health record (EHR) data to identify patterns that enable early sepsis detection. For instance, random forest models have demonstrated high accuracy in predicting sepsis onset in intensive care unit (ICU) patients, while deep learning approaches have been applied to recognize complications such as sepsis-associated acute respiratory distress syndrome (ARDS). Personalized treatment plans developed through AI algorithms predict patient-specific responses to therapies, optimizing therapeutic efficacy and minimizing adverse effects. AI-driven continuous monitoring systems, including wearable devices, provide real-time predictions of sepsis-related complications, enabling timely interventions. Beyond these advancements, AI enhances diagnostic accuracy, predicts long-term outcomes, and supports dynamic risk assessment in clinical settings. However, ethical challenges, including data privacy concerns and algorithmic biases, must be addressed to ensure fair and effective implementation. The significance of this review lies in addressing the current limitations in sepsis management and highlighting how AI can overcome these hurdles. By leveraging AI, healthcare providers can significantly enhance diagnostic accuracy, optimize treatment protocols, and improve overall patient outcomes. Future research should focus on refining AI algorithms with diverse datasets, integrating emerging technologies, and fostering interdisciplinary collaboration to address these challenges and realize AI’s transformative potential in sepsis care.
Evaluating factors that impact scoring an open response situational judgment test: a mixed methods approach
Authors: Iqbal Muhammad Zafar , Ivan Rodica , Robb Colleen , Derby Jillian
Published: January 2025

Introduction

Situational judgment tests (SJT) are commonly used in admissions to measure skills associated with professionalism. Although open-response SJTs have shown strong psychometric properties, assessors’ personal beliefs, experiences, and cultural backgrounds may influence how they perceive, organize and evaluate information within test takers’ diverse responses. Additionally, SJT research typically focuses on reliability and predictive validity, whereas the construct validity of open response SJTs remains underexplored. This mixed methods study aims to address this gap by exploring the construct-(ir)relevant factors that may impact assessors’ evaluation of professionalism in open response SJTs.

Methods

For this study, we used data from Casper, an open response SJT commonly used in professional program admissions. In Study I, a quantitative content analysis was conducted on 160 responses to identify factors which were significant predictors of low and high scores. Correlation coefficients and logistic regression models were used to evaluate the relationship between each factor and response scores. In Study II, think-aloud activities were conducted with 23 Casper assessors to directly observe how they evaluated responses. All interviews were transcribed verbatim, which were then thematically analyzed using an inductive coding technique.

Results

Results from both the content analyses and think-aloud activities revealed that several construct relevant factors influenced scores. Scores were impacted by the extent to which test takers demonstrated the competencies probed for by the SJT, engaged with the context of the presented ethical dilemma, provided in-depth justifications for their response, considered various perspectives relevant to the presented dilemma, and provided creative solutions or insightful arguments for the suggested approach. Mixed results were found with respect to construct irrelevant factors, such as the flow, cohesion, and kinds of phrases used in the response.

Conclusion

This mixed methods study contributes to the construct validity of SJTs by investigating construct relevant and irrelevant factors that may impact assessors’ evaluation of open responses. The findings of this study provide evidence that open-response SJTs are valid approaches to measure professional competencies more broadly, both in terms of what test takers focus on in their responses, as well as in terms of how they construct their responses.
Effects of rocky desertification on soil bacterial community in alpine grasslands of the Qinghai-Tibet Plateau
Authors: Li Shan , Zhou Huakun , Wang Wenying , Ade Haze , Zhang Zhonghua , Ma Li , Wang Zhen , Zhang Qiang , Wei Jingjing , Su Hongye , Qin Ruimin , Shi Zhengchen , Hu Xue , Wu Faliang
Published: January 2025

The makeup of soil microbial communities may serve as a crucial predictor of the alpine grassland ecosystem. Climate change and human disturbance have resulted in intensified ecosystem degradation, such as grassland rocky desertification, which may modify the structures and composition of the microorganisms. However, little is known about the effects of rocky desertification on soil microbial communities of soil. Here, we investigated five different layers of rocky desertification grassland in the Qinghai-Tibet Plateau, including nil rock desertification (NRD); potential rocky desertification (PRD); light rocky desertification (LRD); moderate rocky desertification (MRD); and severe rocky desertification (SRD), we compared soil bacterial community with soil physiochemical properties in different rocky desertification conditions. The result showed that rocky desertification significantly altered the physiochemical properties of the soil but did not significantly affect the bacterial community microbial abundance and diversity. At the same time as rocky desertification increased, soil organic carbon (SOC), total nitrogen (TN), alkali hydrolyzable nitrogen (AN), available phosphorus (AP), and available potassium (AK) decreased significantly, while soil pH, total phosphorus (TP); and total potassium (TK) increased. Redundancy analysis revealed that pH, AK, TP, and SOC are key factors influencing soil bacterial communities. Our finding provides basic information and scientific reference for the restoration of the rocky desertification of alpine grasslands.
How many do we need? Meeting the challenges of studying the microbiome of a cryptic insect in an orchard
Authors: Maurin Apolline , Durand Audrey-Anne , Guertin Claude , Constant Philippe
Published: January 2025

The minimal sampling effort required to report the microbiome composition of insect surveyed in natural environment is often based on empirical or logistical constraints. This question was addressed with the white pine cone beetle, Conophthorus coniperda (Schwarz), a devastating insect pest of seed orchards. It attacks and stop the growth of the cones within which it will spend its life, on the ground. To survive, the bark beetle probably interacts with microorganisms involved in alimentation, cold adaptation, and dormancy stage. Deciphering the drivers and benefits of these microorganisms in an orchard first requires methodological development addressing variability of the white pine cone beetle microbiome. The number of insect guts integrated in composite samples prior to DNA extraction and the number of surveyed trees are two features expected to induce variability in recovered microbiome profiles. These two levels of heterogeneity were examined in an orchard experimental area where 12 white pine trees were sampled and 15 cones from each tree were grouped together. For each tree, 2, 3 and 4 insects were selected, their intestinal tract dissected, and the microbiome sequenced. The number of insects caused no significant incidence on the coverage of bacterial and fungal communities’ composition and diversity (p > 0.8). There was more variability among the different trees. A sampling effort including up to 33 trees in an area of 1.1 ha is expected to capture 98% of the microbial diversity in the experimental area. Spatial variability has important implications for future investigations of cryptic insect microbiome.
Composition and the predicted functions of fungal communities and the key drivers in acidic soils of Jiaodong Peninsula, China
Authors: Liu Jing , Wazir Zafran Gul , Hou Guoqin , Wang Guizhen , Rong Fangxu , Xu Yuzhi , Liu Kai , Li Mingyue , Liu Aiju , Liu Hongliang , Sun Hongwen
Published: January 2025

Introduction

Soil acidification imperils soil health and hinders the agricultural sustainability. As being more tolerant than bacteria to soil acidification, so it would be more meaningful for agricultural management and crop yield to characterize fungal community in acidic soils and manifest its key drivers.

Method

This study investigated the composition and diversity of fungal communities and its key driving factors by collecting 90 soil samples from the acidic region of Jiaodong Peninsula China, spanning 3 × 104 km2.

Results

The results indicated that most soil pH values ranged from 5.01 to 6.42, and the exchangeable acidity (EA) content raised significantly (p < 0.01) along with soil acidic degree increasing. However, no significant differences were found in fungal community diversity and composition among various soil samples, which were all predominantly habited with the phyla of Ascomycota and Basidiomycota. Results of the linear discriminant analysis effect size (LEfSe) analysis revealed that saprophytic fungi were biomarkers of the slightly acidic soil (pH 6.0–6.5), including Nectriaceae, Thielavia, Nectria, Haematonectria, and unclassified Microascaceae, while plant pathogenic fungi, such as Didymellaceae, were biomarkers of the soils pH < 5.5. Similarly, the FUNGuild results also indicated that saprophytic fungi and pathogenic fungi were the dominant functional guilds in the investigated acidic soils, accounting for 66% of the total fungal communities. Redundancy analysis (RDA) revealed that soil pH as well as nitrate nitrogen (NO3−-N) and total nitrogen (TN) significantly associated with fungal community at the phylum level, whilst soil pH was the only factor significantly linked to individual fungal classes (p < 0.01 or 0.05). The further Mantel test analysis and structural equation modeling (SEM) suggested that, in contrast to the negative and directive driving of soil pH on fungal communities' variation, the specific plant pathogenic fungi, Gibberella and Didymellaceae, were significantly and positively associated with soil acidic characteristics (p < 0.05).

Discussion

These findings highlighted that, in addition to modulating the variation of soil fungal community, soil acidification might prime some plant pathogens development. So that, more attentions should be focused on impact of soil acidification on fungal ecology, as well as plant pathogenic fungi.
High prevalence of fecal carriage of extended-spectrum beta-lactamase producing Enterobacterales among patients with urinary tract infections in rural Tanzania
Authors: Macha Magreth Erick , Qi Weihong , Seiffert Salome N. , Bösch Anja , Kohler Philipp , Urassa Honorathy Msami , Haller Sabine , West Erin , Rohacek Maja Weisser , Babouee Flury Baharak
Published: January 2025

Introduction

The global rise of extended-spectrum beta-lactamase-producing Enterobacterales (ESBL-PE) challenges resource-limited countries with insufficient laboratory infrastructure. This study investigates fecal carriage and risk factors for ESBL-PE and carbapenemase-producing organisms among patients with urinary tract infection (UTI) in rural Tanzania.

Methods

This cross-sectional study was conducted at St. Francis Regional Referral Hospital, Ifakara, Tanzania, from October 2021 to August 2023, involving 326 UTI patients. Demographic data and resistance risk factors were collected via structured questionnaires. Stool samples collected pre-antibiotic treatment were screened for ESBL-PE and carbapenemase locally. Positive samples underwent further analysis in Switzerland using MALDI-ToF, Vitek MS, and whole-genome sequencing. Multivariable analysis assessed predictors associated with ESBL-PE carriage for risk factors with p < 0.05.

Results

We enrolled 326 UTI patients (median age: 35.5 years, range: 25–52) and 189 (58.0%) were females. Fecal ESBL-PE colonization was detected in 70.9% of patients, predominantly E. coli (62.8%) and K. pneumoniae (33.0%). Whole-genome sequencing identified diverse phylogroups and sequence types, with CTX-M-15 being the most common ESBL gene. IncF plasmids were the primary carriers. Younger age (aOR: 0.98, 95% CI: 0.97–0.99; p = 0.0239) and inpatient status (aOR: 1.77, 95% CI: 1.08–2.91; p = 0.0036) were significant risk factors for ESBL-PE carriage.

Conclusion

The high prevalence of ESBL-PE fecal carriage in rural Tanzania highlights the need for improved infection control and further research into community transmission dynamics.
Exploring the causal role of plasma metabolites and metabolite ratios in prostate cancer: a two-sample Mendelian randomization study
Authors: Feng Changzhou , Li Haining , Zhang Chu , Zhou Ying , Zhang Huanhuan , Zheng Ping , Zhao Shaolin , Wang Lei , Yang Jin
Published: January 2025

Background

Prostate cancer (PCa), the most prevalent malignant neoplasm in males, involves complex biological mechanisms and risk factors, many of which remain unidentified. By employing a novel two-sample Mendelian randomization (MR) approach, this study aims to elucidate the causal relationships between the circulating metabolome and PCa risk, utilizing comprehensive data on genetically determined plasma metabolites and metabolite ratios.

Methods

For the MR analysis, we utilized data from the GWAS Catalog database to analyze 1,091 plasma metabolites and 309 ratios in relation to PCa outcomes within two independent GWAS datasets. The inverse variance weighted (IVW) method was the primary approach for determining the existence of the causal relationship, supplemented by additional MR methods for heterogeneity, pleiotropy, and cross-validation. The false discovery rate (FDR) and Bonferroni correction were applied to identify the most significant causative associations. Additionally, reverse MR and Steiger filtering were conducted to ascertain whether PCa influenced the observed metabolite levels. Furthermore, metabolic pathway analysis was conducted with MetaboAnalyst 6.0 software.

Results

In the MR analysis, our findings reveal three overlapped metabolite ratios (arginine to glutamate, phosphate to uridine, and glycerol to mannitol/sorbitol) inversely associated with PCa risk. Following FDR correction (FDR < 0.05), cysteinylglycine disulfide was identified as a potential reducer of PCa risk, whereas Uridine and N-acetyl-L-glutamine (NAG) were pinpointed as potential risk factors. Notably, NAG (OR 1.044; 95% CI 1.025–1.063) emerged as a metabolite with significant causal influence, as confirmed by stringent Bonferroni correction (P < 0.05/1400). Steiger’s directionality test (P < 0.001) and reverse MR confirmed the proposed causal direction. Furthermore, metabolic pathway analysis revealed a significant association between the “Glutathione Metabolism” pathway and PCa development.

Conclusion

This study provides novel insights into the potential causal effects of plasma metabolites and metabolite ratios on PCa. The identified metabolites and ratios could serve as candidate biomarkers, contributing to the elucidation of PCa’s biological mechanisms.
Urine kidney injury molecule-1 predicts subclinical kidney disease among persons living with HIV initiating tenofovir disoproxil fumarate-based ART in Zambia
Authors: Chabala Freeman W. , Siew Edward D. , Wester C. William , Brennan Alana T. , Phiri Masauso M. , Vinikoor Michael J. , Masenga Sepiso K. , Aliyu Muktar H.
Published: January 2025

Introduction

Antiretroviral therapy (ART) increases the life expectancy of persons living with HIV (PLWH), but not without potentially serious adverse effects. Tenofovir disoproxil fumarate (TDF) can cause nephrotoxicity, manifesting as acute kidney injury (AKI) that may persist after treatment discontinuation. Kidney injury biomarkers such as kidney injury molecule-1 (KIM-1), retinol-binding protein-4 (RBP-4), interleukin-18 (IL-18), and neutrophil gelatinase-associated lipocalin (NGAL) can aid early diagnosis and predict TDF-associated nephrotoxicity. This study aimed to determine whether the change from baseline in urine KIM-1 (δKIM-1) and NGAL (δNGAL) following 2 weeks of TDF use could predict subclinical TDF-associated nephrotoxicity before the overt manifestation as acute kidney disease after 3 months.

Methods

A prospective cohort study of 205 PLWH was conducted at the Adult Center for Infectious Disease Research (AIDC) in Lusaka, Zambia. ART-naïve PLWH who were starting treatment with TDF with intact kidney function [estimated glomerular filtration rate (eGFR)> 60 mL/min/1.73m2] were followed at initiation, 2 weeks, and approximately 3 months to determine the incidence of TDF-associated nephrotoxicity. We measured urine KIM-1 and NGAL at baseline and after 2 weeks of treatment to determine if it predicted subclinical nephrotoxicity. The presence of TDF-associated nephrotoxicity was defined according to the established acute kidney disease and disorders criteria (AKD) as having either 1) one or more episodes of eGFR< 60ml/min/1.73m2 within 3 months, 2) a reduction in eGFR of greater than 35% (from baseline) within 3 months, and/or 3) an increase in serum creatinine of more than 50% (from baseline) within 3 months.

Results

The incidence of TDF-associated nephrotoxicity was 22%. Baseline eGFR, creatinine, age, female sex, and BMI predicted the risk of overt TDF-associated nephrotoxicity. The median baseline KIM-1-to-creatinine and NGAL-1-to-creatinine ratios of the participants who developed overt TDF-associated nephrotoxicity and those who did not were not significantly different. However, every 1 pg/mg increase in δKIM-1 was associated with a 41% higher risk of TDF-associated nephrotoxicity. No association was observed with δNGAL.

Conclusions

The incidence of TDF-associated nephrotoxicity was high. Change in KIM-1 level within 2 weeks of the initiation of TDF treatment predicted subclinical TDF-associated nephrotoxicity before overt manifestation as acute kidney disease while δNGAL within the same period did not predict subclinical TDF-associated nephrotoxicity.
Ankle joint position sense acuity differences among stroke survivors at three walking ability levels: a cross-sectional study
Authors: Xu Jinyao , Witchalls Jeremy , Preston Elisabeth , Pan Li , Zhang Gengyuan , Waddington Gordon , Adams Roger David , Han Jia
Published: January 2025

Background

Despite the importance of lower limb sensation in walking highlighted in systematic reviews, there is limited research investigating the effect of proprioceptive deficits after stroke and any relationship with walking ability.

Objectives

With stroke survivors of different walking ability, this study aimed to (1) explore side (affected/unaffected) and movement direction (inversion/plantar flexion) effects in ankle joint position sense (JPS) acuity, and (2) compare ankle JPS acuity between groups of stroke survivors with different walking ability.

Methods

Seventy subacute stroke survivors were recruited and divided into three groups based on walking ability, as determined by their gait speed on the 10-Meter Walking Test: household (<0.4 m/s), limited community (0.4–0.8 m/s) and community (>0.8 m/s). Ankle JPS acuity was measured by the active movement extent discrimination apparatus (AMEDA).

Results

A significant difference was found between sides, with the AMEDA scores for the unaffected side significantly higher than for the affected side (F1.67 = 22.508, p < 0.001). The mean AMEDA scores for plantar flexion were significantly higher than for inversion (F1.67 = 21.366, p < 0.001). There was a significant linear increase in ankle JPS acuity with increasing walking ability among stroke survivors (F1.67 = 17.802, p < 0.001).

Conclusion

After stroke, ankle JPS acuity on the affected side was lower than the unaffected side. Stroke survivors had higher ankle JPS acuity in plantar-flexion movements, compared with inversion movements. Overall, stroke survivors with higher ankle JPS acuity tended to have higher walking ability, highlighting the importance of ankle JPS acuity in walking ability after stroke. These findings provide new insights into proprioceptive deficits after stroke and their relevance in neurorehabilitation.
Clinical and analytical monitoring of patients with multiple sclerosis on anti-CD20 therapeutics: a real-world safety profile study
Authors: Fernandes André Aires , Neves Ana Lídia , Ferro Daniela , Seabra Mafalda , Mendonça Teresa , dos Reis Ricardo Soares , Sá Maria José , Guimarães Joana , Abreu Pedro
Published: January 2025

Background

Anti-CD20 monoclonal antibodies are a class of immunosuppressive drugs widely used in the treatment of central nervous system (CNS) inflammatory diseases, with well-established efficacy and safety. Although rare, these therapies can be associated with serious adverse events including hematological and infectious complications. This study aims to evaluate their safety and tolerability profile in real-world clinical practice.

Methods

We conducted a retrospective cohort study comprising patients diagnosed with multiple sclerosis (MS) treated with anti-CD20 drugs since 2016 followed in the Demyelinating Diseases clinic of a tertiary center. Clinical and paraclinical parameters were evaluated, including complete blood count and immunoglobulins measurements.

Results

A total of 160 with multiple sclerosis (pwMS) were included in our study, of whom 110 (68.8%) were female and 147 are currently receiving anti-CD20 therapies. Half of the patients were diagnosed with relapsing–remitting MS, while the remaining had progressive forms, including 23 with primary-progressive MS and 57 with secondary-progressive MS. Eighty-three patients were on ocrelizumab, 48 on rituximab, and 29 on ofatumumab. The mean follow-up duration from the start of anti-CD20 therapy was 30.5 ± 21.3 months. During this period, serious adverse events were observed in 9 patients, including SARS-CoV-2 infection (resulting in one death), urinary tract infection, febrile neutropenia, severe diarrhea, and acute hepatitis. The rate of serious infections in the ocrelizumab subgroup was consistent with the literature, although a higher rate was observed in the rituximab subgroup. A positive correlation was found between serious infectious complications and lower IgG levels. Additionally, longer exposure to anti-CD20 therapy in our cohort was associated with an increased risk of IgG deficiency and a higher incidence of serious infections. Lymphopenia was detected in 25 patients, though it was not directly linked to the occurrence of serious infections.

Conclusion

Our work confirms the tolerability and safety of anti-CD20 drugs in a real-world clinical practice MS cohort, despite their frequent association with analytical changes such as lymphopenia and hypogammaglobulinemia. To better understand the clinical significance of hypogammaglobulinemia secondary to anti-CD20 treatment and to develop strategies for mitigating the associated potential infection risk, future studies with larger populations are essential.
Association between serum albumin and severe impairment of activities of daily living in patients with stroke: a cross-sectional study
Authors: Bi Ranran , Shi Yupeng , Li Manrong , Liu Xiaochen , Ma Zhenchao , Huang Yiqing , Liang Bingyin , Cui Fang
Published: January 2025

Purpose

The relationship between serum albumin levels and severe limitations in ADLs among stroke patients remains unclear. Specifically, the dose–response relationship between the two needs further exploration. This study aims to provide further results.

Materials and methods

This study examined cross-sectional data from patients aged 18 years or older with a diagnosis of stroke confirmed by cranial CT or MRI within 24 h of admission, gathered from January 2020 to August 2022. Data included serum albumin levels, Barthel Index scores recorded after admission, and other essential variables.

Results

The study comprised 2,393 stroke patients. After adjusting for confounding factors, the multivariate analysis revealed a 7% decrease in severe impairment of ADL after stroke for every unit (g/L) increase in serum albumin levels. Compared with individuals with lower serum albumin levels (Q1: ≤ 37.4 g/L), the adjusted odds ratios (OR) for severe of ADL impairment among stroke patients in Q2 (37.4–40.21 g/L), Q3 (40.21–42.80 g/L), and Q4 (≥42.8 g/L) were 0.68 (95% CI: 0.4–1.15, p = 0.148), 0.55 (95% CI: 0.32–0.97, p = 0.04), and 0.64 (95% CI: 0.37–1.15, p = 0.139), respectively. The relationship between serum albumin and severe impairment of ADLs in stroke patients showed an L-shaped curve (non-linear, p = 0.002), with an inflection point at 38.0 g/L. The OR for significant impairment of ADLs was 0.680 (95% CI: 0.568–0.814, p < 0.001) in participants with serum albumin levels <38.0 g/L. However, when serum albumin levels were greater than or equal to 38.0 g/L, the severe impairment of ADLs no longer decreased with rising serum albumin levels.

Conclusion

In summary, an L-shaped connection with an approximate inflection point of 38.0 g/L was found between blood albumin levels and significant ADL impairment in stroke patients. The results of this study suggest that increasing serum albumin levels can significantly help improve the severity of ADL impairment in stroke patients, particularly those with serum albumin levels below 38.0 g/L.
Immediate effects of Vojta Therapy on gait ability in down syndrome patients: a pilot study
Authors: Qian Guoping , Perzanowska Ewelina , Kozakiewicz Mirela , Ewertowska Paulina , Yu Hongli , Ossowski Zbigniew
Published: January 2025

Background

Vojta Therapy (VT) is a neurorehabilitation approach that targets ontogenetic postural function and automatic body posture control. Research has shown its potential to enhance gait ability. However, limited evidence exists regarding its immediate effects on individuals with Down syndrome (DS).

Objectives

This study aimed to assess the immediate effects of one session VT on spatiotemporal gait parameters in individuals with DS.

Design

A non-randomized pilot study was conducted.

Methods

Sixteen individuals with DS (mean age: 17.88 ± 4.57 years, 8 males) participated in this study. Each received a single VT session administered by an experienced physiotherapist. Spatiotemporal gait parameters before and after VT were analyzed using the Vicon motion capture system.

Results

Significant improvements were observed in walking speed (m/s), cadence (steps/min), right step time (s), step length (cm), stride length (cm), and double support time (%GC) following the VT session (P < 0.05). These findings suggest that VT may offer immediate benefits in improving gait parameters for individuals with DS.

Conclusions

Future large-scale studies with more robust designs are necessary to explore the long-term effects of extended VT programs.
Emulation of the subjective experience of visual dorsal stream dysfunction: a description of three in depth case studies
Authors: St Clair Tracy Helen , McDowell Nicola , Dutton Gordon N. , Ravenscroft John , Hay Isobel , Blaikie Andrew
Published: January 2025

These case studies explore the subjective visual experiences of individuals with cerebral visual impairment (CVI), specifically dorsal stream dysfunction (DSD) characterized by simultanagnosia. Through three in-depth case studies, this work documents the challenges these individuals face when navigating cluttered environments. The individuals were asked to describe their visual experiences while watching videos of varying complexity, with the future aim of creating a simulation of simultanagnosia. This process revealed a dynamic constriction of their attentional visual fields as scene complexity increased, and vice versa. Notably, the volunteers experienced a phenomenon where their vision could “get stuck” on specific items, with an apparent concurrent reduction in their ability to perceive and describe visual information as visual clutter increased. These consistent observations indicate that the symptoms of simultanagnosia are not simply limited to perceiving one or two objects at a time but can vary dynamically in response to environmental complexity. They enhance our understanding of how DSD impacts visual search and perceptual experiences, prompting us to propose the term “simultanagnostic vision” to describe this more nuanced and dynamic manifestation of CVI. The results are critical for developing effective interventions and optimizing support strategies for individuals affected by DSD, particularly children at sensitive developmental stages. Furthermore, we recommend deeper investigation into how different visual processing streams in the brain interconnect and influence each other, which may open new avenues for targeted therapeutic interventions.
Change in mineral composition and cooking quality in legumes grown on semi-arid alfisols due to elevated CO2 and temperature
Authors: Shankar K. Sreedevi , Vanaja M. , Shankar Mekala , Siddiqua Asma , Sharma K. L. , Girijaveni V. , Singh V. K.
Published: January 2025

This study aimed to determine the effects of elevated carbon dioxide (eCO2) and temperature (eT) on the phytochemical and nutritional parameters of legumes. Field experiments were conducted using black gram (Vigna mungo L.), green gram (Vigna radiate L.), and pigeonpea (Cajanus cajan L.) genotypes under the Free Air Temperature Elevation (FATE) facility, with three treatments (Ac, eT, and eCO2 + eT) at ICAR-CRIDA, Hyderabad. The results revealed that the negative impact on both phytochemical and nutritional quality was greater under eT compared to eCO2 + eT. Specifically, protein content decreased by 25.6% under eT + eCO2, while the ash content increased by 38.19%. Carbohydrate levels also decreased by 5.53% under these conditions. The reduction in micronutrients (Zn, Fe, Mn, and Cu) was more pronounced than in macronutrients (P, Ca, and Mg) across the three crops. Moreover, principal component analysis (PCA) revealed that the major contributors to PC1 were Mg, crude fiber, cooking time, phosphorus, hydration capacity, ash content, and Mn. The primary contributors to PC2 included swelling capacity, Cu, Mn, carbohydrate, hydration capacity, and Zn. In contrast, the major contributors to PC3 were Ca, Fe, Zn, protein, carbohydrate, swelling index, and ash content. The eigenvalues of principal components, calibrated through different parameters, ranged from 1.052 to 4.755 in black gram and from 1.073 to 6.267 in green gram. This study provides insights into nutritional quality under changing global climate conditions.
Pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections and gut microbiota composition: what do we know?
Authors: Tagi Veronica Maria , Tosi Martina , Greco Ilenia Pia , Stucchi Eliana , Verduci Elvira , Zuccotti Gianvincenzo
Published: January 2025

Post-streptococcal autoimmune neuropsychiatric disorders (PANDAS) are a group of pathological condition characterized by sudden-onset obsessive-compulsive and tic disorders following beta-hemolytic Streptococcus group A (GAS) infection, hypothesized to be caused by autoimmune mechanisms targeting the basal ganglia. Scant literature is available regarding the microbiota composition in children with PANDAS, however few studies support the hypothesis that streptococcal infections may alter gut microbiota composition in these patients, leading to chronic inflammation that may impact the brain function and behavior. Notable changes include reduced microbial diversity and shifts in bacterial populations, which affect metabolic functions crucial for neuroinflammation. Elevated serum levels of sNOX2-dp and isoprostanes indicate oxidative stress, while the presence of lipopolysaccharides (LPS) may contribute to neuroinflammation. The aim of this narrative review is to explore the link between PANDAS and gut microbiota composition. The potential connection between gut microbiota and neuropsychiatric symptoms in PANDAS might suggest the importance of dietary interventions, such as promoting the Mediterranean diet and fiber intake, to reduce the inflammatory state of this patients and therefore improve their outcome.
Case report: a 3-year follow-up on nodal marginal zone lymphoma coexisting with disseminated Talaromyces marneffei infection in a non-endemic area
Authors: Yu Xiping , Xu Houyun , Zhou Junjie , Zhu Zhiqiang , Li Baizhou
Published: January 2025

This case report presents the details of an elderly man in Zhejiang Province of China, who tested human immunodeficiency virus (HIV) negative and subsequently developed Nodal Marginal Zone Lymphoma (NMZL) along with T. marneffei disseminated infection. The study focuses on analyzing the distinct clinical symptoms and pathological manifestations in order to offer precise diagnosis and effective treatment for patients. A 76-year-old male patient was admitted to our hospital due to recurrent fever. An enhanced CT of the abdomen revealed bilateral renal and adrenal mass, along with multiple enlarged lymph nodes in the retroperitoneum. A chest un-enhanced CT showed flaky high-density shadows in the left lung, along with multiple enlarged lymph nodes in the lung hilar, mediastinal regions, and the left supraclavicular side. Subsequently, we conducted a biopsy of the left supraclavicular lymph node and confirmed the NMZL combined with T. marneffei infection. Over 3 years follow-up, there was no recurrence of T. marneffei infection and the lymphoma remained stable. Clinicians and pathologists should remain vigilant about the possibility of T.marneffei infection in non-prone areas. When encountering patients with unexplained fever, swollen lymph nodes, and multiple systems involvement, it is crucial to consider the possibility of lymphoma and fungal infections coexisting.