bluuebunny/crossref_metadata_2025 huggingface dataset:
Sequence-structure based prediction of pathogenicity for amino acid substitutions in proteins associated with primary immunodeficiencies
Authors: Porfireva Ekaterina S. , Zadorozhny Anton D. , Rudik Anastasia V. , Filimonov Dmitry A. , Lagunin Alexey A.
Published: February 2025

Introduction

Primary immunodeficiencies (PIDs) are a group of rare genetic disorders characterized by dysfunction of the immune system components. Early diagnosis and treatment are essential to prevent severe or life-threatening complications. PIDs are manifested by diverse clinical symptoms, posing challenges for accurate diagnosis. A key aspect of PID diagnosis is identifying specific amino acid substitutions in the proteins related with heritable diseases. In this study, we have developed classification sequence-structure-property relationships (SSPR) models for predicting the pathogenicity of amino acid substitutions (AAS) in 25 proteins associated with the most important and genetically studied PIDs and encoded genes: IL2RG, JAK3, RAG1, RAG2, ADA, DCLRE1C, CD40LG, WAS, ATM, STAT3, KMT2D, BTK, FOXP3, AIRE, FAS, ELANE, ITGB2, CYBB, G6PD, GATA2, STAT1, IFIH1, NLRP3, MEFV, and SERPING1.

Methods

The data on 4825 pathogenic and benign AASs in the selected proteins were extracted from ClinVar and gnomAD. SSPR models were created for each protein using the MultiPASS software based on the Bayesian algorithm and different levels of MNA (Multilevel Neighborhoods of Atoms) descriptors for the representation of structural formulas of protein fragments including AAS.

Results

The accuracy of prediction was assessed through a 5-fold cross-validation and compared to other bioinformatics tools, such as SIFT4G, Polyphen2 HDIV, FATHMM, MetaSVM, PROVEAN, ClinPred, and Alpha Missense. The best SSPR models demonstrated high accuracy, with an average ROC AUC of 0.831 ± 0.037, a Balanced accuracy of (0.763 ± 0.034), MCC (0.457 ± 0.06), and F-measure (0.623 ± 0.07) across all genes, outperforming the most popular bioinformatics tools.

Conclusions

The best created SSPR models for the prediction of pathogenicity of amino acid substitutions related with PIDs have been implemented in a freely available web application SAV-Pred (Single Amino acid Variants Predictor, http://www.way2drug.com/SAV-Pred/), which may be a useful tool for medical geneticists and clinicians. The use of SAV-Pred for some clinical cases of PIDs are provided.
Memory B cells and their transcriptomic profiles associated with belimumab resistance in systemic lupus erythematosus in the maintenance phase
Authors: Iwasaki Takeshi , Yoshifuji Hajime , Kitagori Koji , Sumitomo Shuji , Akizuki Shuji , Nakashima Ran , Tsuji Hideaki , Hiwa Ryosuke , Shirakashi Mirei , Murakami Kosaku , Onishi Akira , Onizawa Hideo , Tanaka Masao , Matsuda Fumihiko , Morinobu Akio , Ohmura Koichiro
Published: February 2025

The factors contributing to the treatment efficacy of belimumab in patients with systemic lupus erythematosus (SLE) in the maintenance phase are unknown. Here, we collected blood samples from patients with SLE (n=44) treated with belimumab before and three and six months after treatment. RNA-Seq of whole blood was performed, and gene expression was quantified. Immune cell type enrichment analysis estimated immune cell subtype proportions and gene expression in each subtype. The Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) < 4 at six months was set as the primary efficacy criterion. Non-responders exhibited upregulated B cell proliferation signals before treatment, associated with an increased number of memory B cells. A higher proportion of memory B cells before treatment predicted poor response (p=5.1×10-4). This was also associated with changes in disease activity and glucocorticoid dose at six months compared with baseline. Belimumab did not affect memory B cell proportion during the treatment time course, in contrast to naïve B cells. Higher memory B cell proportion was associated with higher type-I interferon (IFN) scores and lower white blood cell and complement C4 levels. Transcriptomic analysis of memory B cells in non-responders revealed significant upregulation of immunoglobulin genes (Ig). Memory B cells and high Ig expression in them were identified as a treatment-resistant factor of belimumab in SLE patients. Lower C4 and white blood cell counts may serve as clinical markers of higher memory B cells.
Understanding HLA-DQ in renal transplantation: a mini-review
Authors: Das Rajdeep , Greenspan Neil S.
Published: February 2025

Human leukocyte antigen (HLA) mismatching, particularly with HLA-DQ, significantly impacts the development of donor-specific antibodies (DSA) and transplant outcomes. HLA-DQ antibodies are highly immunogenic and detrimental, necessitating advanced high-resolution HLA typing to improve mismatch assessment and clinical risk evaluation. Traditional serological or low-resolution typing often misclassifies mismatches, leading to inaccuracies in assessing immunogenicity and predicting outcomes. Emerging molecular mismatch algorithms refine immunogenicity assessments by analyzing amino acid differences and structural interactions. These tools show promise for personalizing transplant protocols but have limitations, such as variability in predicting individual patient outcomes. Immunogenicity of mismatches also depends on evolutionary divergence and specific amino acid differences, with studies revealing that certain evolutionary lineages and polymorphisms influence T-cell alloreactivity and DSA development. Complexities in HLA-DQ protein expression, including combinatorial diversity of heterodimers and inter-isotypic heterodimers, further complicate risk evaluation. Expression levels, influenced by tissue specificity and inflammatory stimuli, and alternative splicing of HLA-DQ transcripts add additional layers of variability. Future clinical applications, enabled by high-resolution HLA typing, may include refined graft selection, improved DSA monitoring, and individualized therapy. However, understanding the precise mechanisms of HLA-DQ immunogenicity remains a priority for advancing transplantation science and enhancing patient outcomes.
IFNβ drives ferroptosis through elevating TRIM22 and promotes the cytotoxicity of RSL3
Authors: Dong Huiyue , Zhu Ling , Sun Jingjing , Chen Qiuyan , Liu Pengyang , Zhang Wei , Zeng Huajing , Lin Rong , Yu Zongyang , Lu Jun
Published: February 2025

Background

Cyclic GMP-AMP synthase (cGAS)-stimulator-of-interferon genes (STING) pathway is a cytosolic DNA sensor system. The production of this pathway, interferon-β (IFNβ), could suppress the growth of tumor cells, yet it is unclear whether ferroptosis is involved in IFNβ-induced cell death.

Methods

The effects of IFNβ on ferroptosis were analyzed in HT1080, 4T1, HCT116 and 786-O cells. HT1080 and 4T1 cells treated with IFNβ were subjected to RNA-Seq analysis. STAT1, STAT3, TRIM21, and TRIM22 were silenced by siRNAs to examine their effects on IFNβ-induced ferroptosis. The cGAS-STING signaling pathway-activated mice were used to evaluate the effects of IFNβ on ferroptosis in vivo. HT1080 cells, three-dimensional (3D) spheroids, and the xenograft mouse models were treated with IFNβ, RSL3, or IFNβ combination with RSL3 to analyze whether IFNβ enhances RSL3-induced ferroptosis.

Results

Here, we found that IFNβ could promote intracellular Fe2+ and lipid peroxidation levels, and decrease GSH levels in tumor cells. RNA sequencing data revealed that IFNβ induced a transcriptomic disturbance in ferroptosis-related genes. Knockdown of tripartite motif-containing 22 (TRIM22) suppressed the levels of intracellular Fe2+ and lipid ROS. It also reduced heme oxygenase (HMOX1) protein levels and increased ferroptosis suppressor protein 1 (FSP1) levels in HT1080 cells treated with IFNβ. Furthermore, our results illustrated that IFNβ enhanced the RAS-selective lethal 3 (RSL3)-induced ferroptosis and the inhibitory effect of RSL3 on GPX4. Meanwhile, compared to the groups treated with either IFNβ or RSL3 alone, the combination treatment of IFNβ and RSL3 significantly inhibited the growth of HT1080 three-dimensional (3D) spheroids and tumor in a mouse xenograft model.

Conclusions

Our work reveals a role for IFNβ in promoting ferroptosis and provides evidence that IFNβ could be used with RSL3 to increase cytotoxic effects in tumor cells.
Development and assessment of an intestinal tri-cellular model to investigate the pro/anti-inflammatory potential of digested foods
Authors: Ramal-Sanchez Marina , Bravo-Trippetta Chiara , D’Antonio Veronica , Corvaglia Elena , Kämpfer Angela A. M. , Schins Roel P. F. , Serafini Mauro , Angelino Donato
Published: February 2025

Introduction

Immunonutrition, defined as the potential of foods, nutrients and dietary patterns to modulate the immune system activity, has been proposed as a strategy to enhance the immune response in both metabolic and immune-mediated diseases. However, the anti-/pro-inflammatory role of foods and diets is far to be fully ascertained, and thus there is a continued needed for appropriate in vitro cell-culture models to investigate the role of foods in modulating cell-mediated inflammatory processes. This study aims to develop and test an in vitro tri-culture model, simulating the complexity of the intestinal tract and its multiple cell interactions.

Methods

To achieve this, the intestinal epithelial barrier was established by co-culturing human Caco-2 enterocyte-like and HT29-MTX-E12 mucus producing goblet-like colon cells, then adding human monocyte THP-1 cells to the basolateral compartment. The integrity and stability of the epithelial barrier were monitored and the inflammatory response of the model was assessed using various stressors at different concentrations, both individually and in combination (phorbol-12- myristate-13-acetate or PMA, and lipopolysaccharide or LPS), in terms of cytokines production. To test the model, different concentrations of in vitro digested broccoli (BD) were added to the apical section of the model.

Results

Supernatants from the basolateral compartment were collected and analyzed for cytokines production (IL-6, TNF-α, IL-12p70, IL-18 and IL-8) using automated ELISA (ELLA). Additionally, ZO-1 protein from the tight junctions of epithelial cells was analyzed by flow cytometry. The results indicated that 100 nM PMA added to the whole model for 20 h was the best stressor to simulate a mild-inflammatory status of the gut. Following treatment with BD, IL-6, TNF-α, IL-8 and IL-18 were significantly reduced compared to the control group, while ZO-1 expression increased at the lowest BD concentration.

Conclusions

These findings confirm the feasibility of the model for assessing the effects of food digesta on specific cytokines and permeability markers, representing a valuable strategy for investigating the role of foods in modulating the inflammatory response. The results obtained may support dietary strategies aimed at promoting wellbeing and preventing inflammatory-related metabolic diseases.
Advancements in cellular immunotherapy: overcoming resistance in lung and colorectal cancer
Authors: Qin Lijuan , Li Yuan , Liu Juan , An Xiaoqin
Published: February 2025

Immunotherapy has revolutionized cancer treatment, offering hope for patients with otherwise treatment-resistant tumors. Among the most promising approaches are cellular therapies, particularly chimeric antigen receptor T-cell (CAR-T) therapy, which has shown remarkable success in hematologic malignancies. However, the application of these therapies to solid tumors, such as lung and colorectal cancers, has faced significant challenges. Tumor resistance mechanisms—ranging from immune evasion, antigen loss, and immune checkpoint upregulation, to tumor microenvironment immunosuppression—remain major obstacles. This mini-review highlights the latest advancements in tumor immunotherapy, with a focus on cellular therapies, and addresses the resistance mechanisms that hinder their effectiveness in lung and colorectal cancers. We examine the evolution of CAR-T cell therapy, as well as the potential of engineered natural killer (NK) cells and macrophages in solid tumor treatment. The review also explores cutting-edge strategies aimed at overcoming resistance, including combination therapies, gene editing technologies, and nanotechnology for targeted drug delivery. By discussing the molecular, cellular, and microenvironmental factors contributing to resistance, we aim to provide a comprehensive overview of how these challenges can be overcome, paving the way for more effective, personalized immunotherapies in lung and colorectal cancer treatment.
The impact of L1 literacy on the production of Spanish verbal passives by school-age Spanish heritage speakers
Authors: Armstrong Andrew , Montrul Silvina
Published: February 2025

Acquiring literacy contributes to monolingual children's language development, especially with the oral production of complex sentences. However, less is known about how written language exposure impacts first language (L1) morphosyntactic growth in Spanish-speaking children in the U.S., who are educated in their second language (L2) and have little opportunities to develop L1 literacy. To investigate this, we evaluated 8–12-year-old Spanish heritage speakers' (HSs) L1 production accuracy of grammatical gender and full verbal passives using picture description and elicited imitation (EI) tasks. One group of HSs attended bilingual (English-Spanish) schools and had developed strong L1 literacy skills; the other group attended English-only schools and had weaker L1 literacy skills, confirmed with standardized literacy tasks. The children receiving literacy instruction and textual exposure in Spanish (the L1) outperformed those attending schools in English only, producing gender agreement more accurately and full passives more accurately. They also outperformed the children in English-only schools in literacy and cognitive measures. These findings indicate that experience with textual input via L1 literacy development is an effective way to aid the acquisition and production of complex linguistic forms in HSs during the school-age period.
The effects of vessel speed and size on the lethality of strikes of large whales in U.S. waters
Authors: Garrison Lance P. , Lisi Niki E. , Gahm Meghan , Patterson Eric M. , Blondin Hannah , Good Caroline P.
Published: February 2025

Vessel strikes are a substantial source of mortality for large whales worldwide and may pose conservation threats for small populations. Model-based estimates of mortality rates, which inform management strategies to reduce vessel strike mortality, typically assume a reduced likelihood that a whale-vessel collision will be lethal to the whale at slower vessel speeds. In this study, we reviewed and updated available data on observed whale-vessel interactions in U.S. waters and developed a new model characterizing the probability that an interaction will be lethal to the whale as a function of vessel speed, length (as a proxy for mass), and whale taxon. We found a significant effect of vessel size class on the probability of lethality. In addition, decreasing vessel speeds reduced the likelihood of a lethal outcome for all vessel size classes, but this effect was strongest for vessels less than 108m in length. The probability that a strike by a very large ocean-going vessel will be lethal exceeded 0.80 at all speeds above 5 knots. Whale taxon also affected both the likelihood of a lethal strike and the effect of vessel speed. Humpback whales (Megaptera novaeangliae) had significantly lower rates of lethal strikes compared to other large whales. This difference may be associated with data limitations, differing behavioral responses between species, varying vessel types between regions or differences in body composition and blubber thickness. The model is consistent with biophysical models that demonstrate a high rate of strike lethality for large vessels with high masses. Vessel speed restrictions are one of the primary approaches to reduce the risk of vessel strikes to whales in the face of continued industrialization of the oceans, and the model presented here will help better inform management efforts.
Rockfish abundance, recruitment, and community structure trends in the western Strait of Juan de Fuca, Washington, 2005-2023
Authors: Larson Shawn E. , Shelledy Katie , Escontrela Dieguez Daniela , Christiansen Jeff , Olsen Amy Y. , Randell Zachary , Williams Megan H. , VanDamme Chris , Lowry Dayv , Jasper William
Published: February 2025

Rockfish, Sebastes spp., are bottomfish that come in a variety of shapes, sizes and colors with 28 species recognized in the Salish Sea. Based on increasing concern over the long-term stability of rockfish populations in Washington by state and federal agencies, the Seattle Aquarium formalized a benthic monitoring program starting in 2005 on rocky reefs west and east of Neah Bay, Washington. Diver-operated video (DOV) surveys were conducted annually to quantify patterns in bottomfish (rockfish and other species associated with rocky reefs) abundance and stability over time. Divers performed 100-meter video transects devised to be both non-invasive and repeatable, for assessing both relatively sessile bottomfish and for schooling, transitory rockfish species. Strip transects were conducted annually in August from 2005 through 2023 at five permanently marked index sites. Species-specific relative abundance data for bottomfish were later extracted by biologists from archived video. Notably, over the 19-year study period, bottomfish abundance was stable or increased at all sites, driven by significant increases in eight rockfish species: Black/Deacon, Canary, China, Copper, Quillback, Tiger, and Yellowtail. Relatively few Puget Sound, Vermillion, Widow, and Yelloweye Rockfish individuals were documented, and their abundance did not increase throughout the study. Boccaccio where never encountered during the 19 year monitoring period. All sites displayed relative stability in fish community structure over time. We documented low levels of young-of-the-year (YOY) rockfish recruitment over the years with one major recruitment event in 2016. Despite an increase in abundance across eight rockfish species, recruitment events remained infrequent. Furthermore, Boccaccio and Yelloweye rockfish, both protected species, were either never or rarely encountered, respectively, underscoring the need for sustained conservation efforts and expanded long-term monitoring for species with long generation times such as rockfish.
Impact of anthropogenic activities on the biodiversity of macrobenthos and benthic ecological quality in the mudflats of Hwangdo Island, South Korea: field surveys and remote sensing assessments
Authors: Liang Jian , Ma Chae-Woo
Published: February 2025

Introduction

As coastal urbanization progresses, anthropogenic activities have significantly impacted mudflats. In South Korea, land reclamation and aquaculture have drastically altered mudflat ecosystems.

Methods

In our study, we utilized five remote sensing indices to assess the impact of anthropogenic activities on Hwangdo Island. We supplemented this with field surveys to evaluate macrobenthic biodiversity and benthic ecological quality, investigating their relationship to anthropogenic activities.

Results and discussion

Spearman’s correlation analysis revealed that terrestrial ecological quality influences macrobenthic biodiversity. The abundance of the predominant species, Pirenella sp., was primarily influenced by normalized differential build-up and bare soil index (NDBSI). Furthermore, biota-environment matching (BIO-ENV) analysis, distance-based multivariate analysis for a linear model (DisLM), and distance-based redundancy analysis (dbRDA) all pinpointed NDBSI as the predominant factor impacting macrobenthic communities in the mudflats of Hwangdo Island. Seasonal changes in NDBSI were mainly attributed to variations in bare soil area resulting from agricultural activities on Hwangdo Island. Overall, macrobenthic communities in the mudflats of Hwangdo Island are mainly indirectly affected by agricultural activities. Moreover, our study offers a fresh perspective on the conservation of Hwangdo Island’s mudflats and provides critical references for the South Korean government in crafting and implementing mudflat protection policies.
Case report: The value of early application of mNGS technology in the diagnosis and treatment of severe Legionnaires’ disease: reports of two cases with different outcomes
Authors: Fang Jianqing , Wang Zhe , Shen Yu , Wu Xuenong , Fang Hao , Sun Xiaokui , Yu Ting , Zhang Qingqing
Published: February 2025

Background

Legionnaires’ disease has a high clinical mortality rate, and early diagnosis and treatment are critical. Increasing evidence shows that metagenomic next-generation sequencing (mNGS) has excellent potential for the early identification of pathogens. To help clinicians better recognize Legionnaires’ disease in its early stage and to illustrate the diagnostic value of mNGS technology, we reviewed and summarized two cases of severe Legionnaires’ disease.

Methods and analysis

We selected two patients with severe Legionnaires’ disease who were admitted to our department in recent years. We discuss experience with them and the shortcomings in their treatment by summarizing their medical history, disease evolution, tests, and diagnostic and therapeutic processes.

Results

In both patients, the diagnosis of Legionnaires’ disease was confirmed through analysis of the bronchoalveolar lavage fluid (BALF). The middle-aged male patient was cured and discharged due to early detection and diagnosis. The elderly immunocompromised patient died due to a delay in diagnosis.

Conclusion

This study highlights the importance of the early recognition and diagnosis of severe Legionnaires’ disease and the advantages of mNGS in identifying the pathogen.
Association of dietary niacin intake with osteoporosis in the postmenopausal women in the US: NHANES 2007–2018
Authors: Li Li , Liang Wankun , Deng Bing , Jiang Yue , Huang Xiaomin , Zhang Yanlin , Lu Tianrui , Wang Lu , Xu Yunxiang , Chen Guizhen
Published: February 2025

Background

Elderly individuals with inadequate vitamin B level are at increased risk of degenerative conditions, notably cardiovascular disorders, cognitive impairments, and osteoporosis. The relationship between niacin (vitamin B3) consumption and osteoporosis risk remains a subject of debate. This study aimed to clarify the relationship between dietary niacin intake and the incidence of osteoporosis in postmenopausal women aged ≥50 years.

Methods

In this study, we gathered details on participants’ bone mineral density, osteoporosis status, dietary niacin intake, and several other critical variables. Multivariate logistic regression models were constructed to determine the association between dietary niacin intake and the incidence of osteoporosis. Restricted cubic splines were employed to further assess the linearity and explore the shape of the dose-response associations. Additionally, we performed stratified and interaction analyses to illustrate the stability of the observed relationships across different subgroups.

Results

After adjusting for all covariates, there was a significant inverse association with osteoporosis (OR = 0.87; 95% CI: 0.77–0.97; p = 0.016). A negative relationship was observed between dietary niacin intake and the risk of osteoporosis (nonlinear: p = 0.672). While stratified analyses revealed some differences in the association between dietary niacin intake and osteoporosis risk, these differences were not statistically significant.

Conclusion

Dietary niacin intake exhibited an inverse correlation with the incidence of osteoporosis. The risk of osteoporosis was significantly reduced by 13% with every 10 mg/day increase in daily dietary niacin consumption among postmenopausal women.
Case report: Primary cardiac synovial sarcoma with suspected connective tissue disease diagnosed by EBUS-TBMB
Authors: Feng Yanmei , Wu Chunxia , Chi Jing , Li Linying , Wang Pu , Guo Rui
Published: February 2025

Primary cardiac synovial sarcoma (PCSS) most commonly originates in the right atrium of the heart and is exceptionally rare. Although biomarkers of autoimmune diseases, such as antinuclear antibodies (ANAs), have been reported as potential indicators of certain tumors, the association between PCSS and ANAs remains unclear. Herein, we describe a case of pleural effusion that was initially considered to be due to connective tissue disease (CTD) but was finally diagnosed as PCSS through endobronchial ultrasound-guided transbronchial mediastinum biopsy (EBUS-TBMB). Clinicians need to update their knowledge regarding the potential association between PCSS and ANAs. This case report also emphasizes the importance of EBUS-TBMB, under the guidance of positron emission tomography/computed tomography (PET/CT), in the diagnosis of this rare tumor in an unusual location.
Does quercetin affect tendon healing? An experimental study in a rat model of Achilles tendon injury
Authors: Yurteri Ahmet , Mercan Numan , Çelik Zeliha Esin , Yaykaşlı Hakan , Yıldırım Ahmet
Published: February 2025

Purpose

The objective of this study was to investigate the impact of quercetin, a potent antioxidant, on tendon healing utilizing a rat Achilles tendon injury model.

Materials and methods

The study involved 32 male Wistar-Albino rats, randomly split into experimental (quercetin) and control groups, each with 16 rats. A bilateral Achilles tenotomy model was applied, with the experimental group receiving quercetin and the control group receiving corn oil via oral gavage from surgery until sacrifice. One Achilles tendon per rat underwent histopathological and immunohistochemical evaluations, while the other underwent biomechanical analysis.

Results

Tendons were evaluated histopathologically in terms of tenocyte, ground substance, collagen, and vascularity, and quercetin was observed to significantly increase tendon healing in the experimental group (p-values = 0.0232, 0.0128, 0.0272, 0.0307, respectively). In the immunohistochemical analysis, type I collagen, type III collagen, alpha smooth muscle actin (SMA), and Galectin-3 were evaluated, and it was observed that quercetin increased tendon healing (p-values = 0.0166, 0.0036, 0.0323, 0.0295, respectively). In the biomechanical analysis, the rupture strength was evaluated with six parameters (failure load, maximum energy, displacement, stiffness, ultimate stress, and strain), and it was observed that quercetin significantly increased the rupture strength (p-values = 0.032, 0.014, 0.026, 0.025, 0.045, 0.012, respectively).

Conclusion

Quercetin significantly enhanced tendon healing both biomechanically and immunohistochemically. However, further clinical studies are needed to understand its effects on human tendon healing, as this is the first study of its kind.
Impact of pre-pregnancy body mass index on preeclampsia
Authors: Mao Jing , Sun Hanxiang , Shen Qinxin , Zou Chang , Yang Yuanyuan , Du Qiaoling
Published: February 2025

Background

It remains unclear how pre-pregnancy body mass index (BMI) affects preeclampsia in the Chinese population, primarily due to insufficient large-scale research on this topic.

Objective

The study aimed to determine the relationship between pre-pregnancy BMI and (severe) preeclampsia in the Chinese population, providing a detailed description of the findings.

Methods

The retrospective study included a total of 75,773 pregnant women registered between 2016 and 2020. These participants were categorized into four groups based on their pre-pregnancy BMI: underweight (BMI < 18.5 kg/m2), normal weight (BMI 18.5–<24 kg/m2), overweight (BMI 24–<28 kg/m2), and obese (BMI ≥ 28 kg/m2). The relationship between risks of preeclampsia or severe preeclampsia and pre-pregnancy BMI were further explored, with an evaluation of potential modification by maternal age.

Results

A lower risk of developing preeclampsia was observed in the underweight population, with an OR of 0.604 (95%CI, 0.507–0.719). In contrast, women who were overweight or obese during the pre-pregnancy period demonstrated a significantly higher risk of preeclampsia, with ORs of 2.211 (95%CI, 1.967–2.486) and 3.662 (95%CI, 3.026–4.431), respectively. After adjusting for confounding factors, the elevated risk of preeclampsia persisted, showing ORs of 2.152(95%CI, 1.911–2.425) for the overweight population and 3.493 (95%CI, 2.874–4.245) for those who were obese, while the risk for underweight women remained lower, with an OR of 0.609(95%CI, 0.511–0.727). For severe preeclampsia, the risk was also higher in the overweight and obese participants after adjusting for confounders, demonstrating ORs of 1.652(95%CI, 1.364–2.001) and 2.762(95%CI, 2.014–3.788), respectively. The underweight population exhibited a lower risk of severe preeclampsia, with an OR of 0.720(95%CI, 0.565–0.919). In addition, these risks were not significantly associated with maternal age.

Conclusion

Regardless of adjustment for confounders, underweight women demonstrated a lower risk of preeclampsia, whereas the overweight/obese population exhibited a higher occurrence of both preeclampsia and severe preeclampsia. These associations were not influenced by maternal age.
Multidrug resistance of Pseudomonas aeruginosa: do virulence properties impact on resistance patterns?
Authors: Saha Poulomi , Kabir Rubaiya Binte , Ahsan Chowdhury Rafiqul , Yasmin Mahmuda
Published: February 2025

Introduction

Patients with nosocomial infections are at risk of multidrug-resistant (MDR) Pseudomonas aeruginosa since these bacteria slow down the entire treatment process, increasing the morbidity and mortality of patients staying in hospital. The purpose of the research was to assess the simultaneous presence of multidrug resistance and virulence factors among nosocomial strains of P. aeruginosa to evaluate significant association among them.

Methods

One hundred and eight clinical isolates of P. aeruginosa were found in a variety of samples taken from patients having nosocomial infection, including wound swabs, pus, sputum, tracheal aspirate, and urine. An antibiogram was performed to investigate the pathogen’s antibiotic sensitivity pattern against 14 widely used antibiotics in Bangladesh. Virulence factors were evaluated, and the presence of ten β-lactamase and six virulence genes was analyzed by performing PCR. By using a binary logistic regression test with a 95% confidence interval, the relationship between MDR phenotypes and the virulence attributes was assessed.

Results

The susceptibility rate among the isolates was 70–75% for aminoglycosides (amikacin, gentamicin, netilmicin), 15–20% for cephalosporins (ceftazidime, ceftriaxone), 30–35% for quinolones (ciprofloxacin, levofloxacin), 10–15% for tetracyclines (tigecycline, doxycycline), 15–20% for carbapenem (meropenem), 10–15% for sulfonamide (co-trimoxazole), 5–10% for amoxiclav, and 30–35% for piperacillin/tazobactam. A total of 74.1% of the strains carried metallo-β-lactamase (MBL) genes. Among the isolates, 89% showed hemolytic activity, 80–90% produced different pigments such as fluorescein and pyoverdine, 46% were strong biofilm producers, and all the isolates presented different types of motilities (swimming, swarming, and twitching). The virulence genes (lasB, exoS, toxA, aprA, algD, and plcH) were detected within a range of 60–80% of the isolates.

Discussion

Only the toxA gene and twitching motility showed a significant correlation (p-value = 0.001 and 0.028, respectively) with multidrug resistance in the clinical P. aeruginosa isolates which indicates that it can be used as a drug target to combat these organisms. The high prevalence of MDR strains and their association with virulence factors revealed the potential of the pathogen to cause an infection. The current study advocates for immediate epidemiological surveillance of MDR P. aeruginosa strains in Bangladesh to impede the rapid dissemination of this opportunistic pathogen.
Genomic characterization and evolutionary analysis of a Getah virus variant from piglets in central China
Authors: Guo Zhenhua , Jiang Yao , Li Peng , Zhang Gaiping
Published: February 2025

Introduction

As a re-emerging mosquito-borne virus, Getah virus (GETV) has been found in more than 10 countries surrounded by the Pacific Ocean and shows a broadly host tropism, raising concerns for the potential risk to public health. Horses and pigs are susceptible to GETV and play pivotal roles to the GETV adaptive evolution.

Methods

Here, we reported a GETV outbreak in a pig farm with 20% suckling piglets losses. The genomic characteristics and evolutionary relationship of the pathogenic viral strain were also analyzed.

Results

The isolate GETV-HeN202309 shared the highest nucleotide identity of 99.8% with strains from Guangdong and Sichuan province, suggesting it is an imported transmission. Although the phylogenetic analysis divided GETV into four groups (groups I–IV), only strains in group III were dominant and widely circulating in the fields. Furthermore, several amino acid substitutions in E2 protein were identified among different GETV groups and the substitution at D262th N site led to an additional glycosylation modification. Besides, six amino acid sites were under positive selection of E2 protein. Most of these special sites were distributed in domain A, B, and C of E2 protein, which are usually associated with the GETV infection and immune response.

Discussion

Our study expands knowledge of GETV pathogenicity and deepens understanding of GETV genetic and adaptive evolution, which would be valuable for the development of diagnosis and prevention for GETV.
Decoding the anomalies: a genome-based analysis of Bacillus cereus group strains closely related to Bacillus anthracis
Authors: Magome Thuto Gomolemo , Surleac Marius , Hassim Ayesha , Bezuidenhout Cornelius Carlos , van Heerden Henriette , Lekota Kgaugelo Edward
Published: February 2025

Introduction

The Bacillus cereus group encompasses a complex group of closely related pathogenic and non-pathogenic bacterial species. Key members include B. anthracis, B. cereus, and B. thuringiensis organisms that, despite genetic proximity, diverge significantly in morphology and pathogenic potential. Taxonomic challenges persist due to inconsistent classification methods, particularly for B. cereus isolates that resemble B. anthracis in genetic clustering.

Methods

This study investigated B. cereus group isolates from blood smears of animal carcasses in Kruger National Park, uncovering an unusual isolate with B. cereus features based on classical microbiological tests yet B. anthracis-like genomic similarities with an Average Nucleotide Identity (ANI) of ≥95%. Using comparative genomics, pan-genomics and whole genome Single Nucleotide Polymorphism (wgSNP) analysis, a total of 103 B. cereus group genomes were analyzed, including nine newly sequenced isolates from South Africa and a collection of isolates that showed some classification discrepancies, thus classified as “anomalous.”

Results and discussion

Of the 36 strains identified as B. anthracis in GenBank, 26 clustered phylogenetically with the four confirmed B. anthracis isolates from South Africa and shared 99% ANI. Isolates with less than 99% ANI alignment to B. anthracis exhibited characteristics consistent with B. cereus and/or B. thuringiensis, possessing diverse genetic profiles, insertion elements, resistance genes, and virulence genes features, contrasting with the genetic uniformity of typical B. anthracis. The findings underscore a recurrent acquisition of mobile genetic elements within B. cereus and B. thuringiensis, a process infrequent in B. anthracis.

Conclusion

This study highlights the pressing need for standardized taxonomic criteria in B. cereus group classification, especially as anomalous isolates emerge. This study supports the existing nomenclature framework which offers an effective solution for classifying species into genomospecies groups. We recommend isolates with ANI ≥99% to standard reference B. anthracis be designated as typical B. anthracis in GenBank to maintain taxonomic clarity and precision.
A comprehensive method on black-legged tick larvae and nymph feeding on mice to study Lyme disease transmission and acquisition
Authors: Scholl Aaron , Li Bingjie , Dennis John , De Sandip
Published: February 2025

Tick-borne diseases are a growing public health concern in the United States, with cases rising steadily each year. Lyme borreliosis, or Lyme disease, remains the most prevalent, affecting approximately 476,000 individuals annually. Human-driven changes in climate and ecosystems have expanded the habitat of pathogen-carrying ticks, facilitating the spread of these infections. Additionally, increased instances of tick-borne diseases transmission through human tissues have been reported. Despite ongoing efforts to manage these infections, their incidence continues to rise. To develop effective control measures against these diseases and prevent the transmission of tick-borne infections through human and animal tissues, it is very important to develop detection assays and understand the transmission mechanisms of tick-borne infections. In this study, we provide detailed descriptions and visual references for larval and nymphal tick feeding on mice, focusing on the transmission and acquisition of Borrelia burgdorferi (sensu stricto). These methodologies can be applied to study other tick-borne diseases, tick vectorial capacity, and tick biology, aiding in the development of detection strategies to combat these infections.
Comparison of self-collected and healthcare worker-collected rectovaginal swabs for group B streptococcus detection in pregnancy using PCR with a commercial collection-enrichment device
Authors: Kukovica Iva , Omahen Neža , Klobučar Nika , Bučar Martina , Franko Rutar Anita , Perme Tina , Lučovnik Miha , Jeverica Samo
Published: February 2025

Introduction

Universal screening for the detection of group B streptococcus (GBS) colonization in pregnant women was recently introduced in Slovenia. The aim of our study was to determine whether self-collection of rectovaginal swabs is a valid alternative to collection by healthcare workers (HCWs).

Methods

A prospective, multicenter study was conducted between June and November 2023. A total of 227 pregnant women (aged 20 to 44 years) from the University Medical Center Ljubljana (n = 136), the Novo mesto Community Health Center (n = 48) and the Trebnje Community Health Center (n = 43) were included. Two swabs were taken: swab A by the HCWs using standard semi-solid Amies transport medium (Meus; current standard) and swab B by the pregnant woman following visual instructions using a commercial LIM Broth (Copan). Swabs were inoculated onto ChromID Strepto B (STRB) agars directly and after overnight enrichment in LIM broth. The NeuMoDx GBS assay was performed from the enrichment broth. A self-assessment questionnaire was completed after sampling. Performance characteristics were calculated and compared between different diagnostics test algorithms using McNemar’s test for paired samples.

Results

Overall, GBS was detected in 18% (95% CI 13–23%; n = 40) of swabs A and 19% (95% CI 14–25%; n = 43) of swabs B. PCR was superior in both groups. In the group of swabs collected by HCWs, 4 (40 vs. 36; 11.1% difference; p = 0.046) and 3 (40 vs. 37; 8.1% difference; p = 0.083) additional positives were detected with PCR compared to direct and enrichment culture, respectively; in the group of self-collected swabs, 4 (43 vs. 39; 10.3% difference; p = 0.046) and 6 (43 vs. 36; 16.2% difference; p = 0.014) additional positives were detected with PCR compared to direct and enrichment culture, respectively. Self-collection showed a trend towards a higher diagnostic yield. PCR after enrichment from self-collected samples was found to be the most sensitive method overall. 58.5% (n = 124/212; 95% CI 52–65%) of women would prefer the swabs taken by HCWs.

Discussion

Self-collection of rectovaginal swabs during pregnancy is a good alternative to HCW-collected swabs. PCR from enrichment broth was better for the detection of GBS compared to enrichment culture. Majority of women preferred swabs taken by HCWs.
A systematic review of the efficacy of repetitive transcranial magnetic stimulation in treating dysarthria in patients with Parkinson's disease
Authors: Chen Kerong , Zhou Sitong , Lu Shiyu , Qin Yuliang , Li Xinyao , Li Yi , Liu Tianyun , Zhang Mei , Xu Kun , Shi Hongping , Lv Xiaoman , Yuan Kai , Shi Hongling , Qin Dongdong
Published: February 2025

Objective

To analyze the literature on the efficacy of repetitive transcranial magnetic stimulation (rTMS) in treating dysarthria in patients with Parkinson's disease (PD) and provide a reference for targeted clinical treatment of dysarthria in PD patients.

Methods

A systematic search was conducted in English and Chinese databases, including Embase, Cochrane, Medline, PubMed, CNKI, Wanfang, Chinese Biomedical Literature Database, and VIP Database, for relevant literature on rTMS treatment for dysarthria in PD patients. The search timeframe was from the inception of each database to October 2023. Literature was screened according to inclusion and exclusion criteria. Two researchers extracted information on study subjects, age, intervention methods, intervention duration, intervention frequency, evaluation indicators, and intervention results from the included literature. The modified Jadad scale was used to evaluate the quality of the literature.

Results

A total of seven studies were included, mainly focusing on the frequency, duration, and stimulation site of rTMS for dysarthria in PD patients. Six studies indicated that rTMS treatment improved dysarthria in PD patients.

Conclusion

Repetitive transcranial magnetic stimulation has a positive effect on improving dysarthria in PD patients, but further research is needed to determine its efficacy.
Role of visual function and performance of activities of daily living in cognitive function in patients with mild cognitive impairment: a cross-sectional study
Authors: Zhou Chunhui , Yang Ganfeng , Theeboom Marc , Yang Hua , Zhu Ruiting , Zhou Zijian , Zhu Dong
Published: February 2025

Background

Mild cognitive impairment (MCI) is a precursor to dementia, with many patients showing early decline in activities of daily living (ADLs). However, the role of visual impairment in this process is underexplored despite evidence suggesting it may accelerate cognitive decline. Current research does not understand how visual dysfunction affects cognitive abilities and how ADLs might moderate this relationship. This gap is crucial because early interventions targeting visual impairments could potentially delay progression to dementia, offering new avenues for supporting MCI patients.

Objective

This study investigates the relationship between visual function and cognitive abilities in patients with MCI. Specifically, it seeks to determine how different aspects of visual function, such as visual field indices and visual acuity, correlate with various cognitive domains measured by standardized assessments. Additionally, the study aims to examine the role of ADLs as a potential moderating factor in this relationship. By analyzing how ADL performance influences the strength and direction of the association between visual impairments and cognitive function, this research intends to identify key areas where visual deficits may contribute to cognitive decline in MCI.

Methods

This is a cross-sectional study. Two hundred and seventy four elderly patients were diagnosed with MCI from various communities in Taicang City, Jiangsu Province, China. Most participants were women (68.6%), and the average age was 69 years. Notable comorbidities included hypertension (41.6%) and diabetes (33.2%), indicating a higher burden of health conditions than typical older adult populations. Visual function, Montreal Cognitive Assessment (MoCA), and the ADLs were measured. Pearson's correlation coefficients were used to examine the unadjusted associations between visual function measures and cognitive performance. Multivariable linear regression models were employed to further explore these relationships and to assess the moderating role of ADLs.

Results

Significant positive correlations were found between visual function and cognitive performance, particularly with Visual Function Index (VFI) showing a strong initial correlation with the total MoCA score (r = 0.61, p < 0.001), which was attenuated after adjusting for ADL (β = 0.06, p = 0.23). Maximum Visual Field (Max VF) was positively correlated with language skills (r = 0.13, p < 0.05). The negative correlation of Minimum Visual Field (Min VF) with cognitive performance became positive after ADL adjustment (β = 0.12, p = 0.04).

Conclusions

These findings suggest that visual function plays a crucial role in the cognitive and functional abilities of patients with MCI. Early interventions targeting visual impairments may help mitigate cognitive decline and improve the quality of life for these patients.
Modeling dynamics on the dance floor with directional swarmalators
Authors: Toiviainen Petri , Bamford Joshua S. , Thompson Marc R.
Published: February 2025

Understanding collective behavior in both biological and social contexts, such as human interactions on dance floors, is a growing field of interest. Spatiotemporal dynamics of collective behavior have previously been modeled, for instance, with swarmalators, which are dynamical units that exhibit both swarming behavior and synchronization, combining spatial movement and entrainment. In our current study, we have expanded the swarmalator concept to encompass gaze direction as a representation of visual attention. We employ the newly developed directional swarmalator model for simulating the complex spatiotemporal dynamics observed on dance floors. Our model aims to reflect the complex dynamics of collective movement, as well as rhythmic synchronization and gaze alignment. It establishes a quantitative framework to dissect how individuals on dance floors self-organize and generate emergent patterns in response to both musical stimuli and visual perception of other dancers. The inclusion of gaze direction allows for the simulation of realistic scenarios on dance floors, mirroring the dynamic interplay of human movement in rhythm-driven environments. The model is initially tested against motion capture recordings of two groups dancing in a silent disco, however, it is theoretically adaptable to a variety of scenarios, including varying group sizes, adjustable degrees of auditory and visual coupling, as well as modifiable interaction ranges, making it a generic tool for exploring collective behavior in musical settings. The development of the directional swarmalator model contributes to understanding social dynamics in shared music and dance experiences.