bluuebunny/crossref_metadata_2025_split huggingface dataset:
Characterization and genomic analysis of a Herelleviridae bacteriophage UHP46 infecting mastitis-causing Staphylococcus aureus
Authors: Najeeb Sara , Khan Imran , Muhammad Javed , Jahangir Muhammad , Alvi Iqbal Ahmad , Abbas Anza , Ullah Aman , Ullah Arif , Sajjad Wajiha , Khan Hashir , Khan Amjad 
Published: February 2025

BackgroundMastitis is a widespread disease on a global scale, significantly impacting the dairy industry. Mastitis in dairy cattle is caused by over 150 different bacteria, with Staphylococcus aureus (S. aureus) playing a significant role in financial losses, problems with animal welfare, and challenges with food safety. Phage treatment is thus being investigated as an effective replacement for reducing contaminants and illnesses caused by bacteria. In this study, we identified a phage UHP46, that effectively targets mastitis-causing S. aureus.MethodsS. aureus S46 was used to screen for the wastewater lytic phages. The isolated lytic phage UHP46, which formed clear plaques and spots, was further characterized.ResultsPhage UHP46, belonging to the Herelleviridae family, forms clear, circular plaques in bacterial lawn. UHP46 showed stability under various range of temperature and pH levels, with maximum activity observed at pH 7 and temperature 37°C. Genomic analysis revealed that phage UHP46 is a dsDNA virus with an approximate genome size of 139,731 bp, and it encodes 72 proteins with known functions and 136 hypothetical proteins. One-step growth curve analysis indicated latent period of approximately 20 mins and burst size of about 27 progeny/cell. In organic stability test, UHP46 showed stability in DMSO and acetone. Furthermore, it effectively inhibited S. aureus growth for up to 16 h, suggesting its suitability for therapeutic applications against S. aureus infections.ConclusionThese findings suggest that phage UHP46 could serve as a promising alternative to antibiotics for managing S. aureus- induced mastitis, contributing to dairy production and improved animal health.
Whole genomic analysis uncovers high genetic diversity of rifampicin-resistant Mycobacterium tuberculosis strains in Botswana
Authors: Mogashoa Tuelo , Loubser Johannes , Choga Ontlametse T. , Ngom Justice Tresor , Choga Wonderful T. , Mbulawa Mpaphi B. , Molefi Tuduetso , Stephen One , Makhondo Topo , Seru Kedumetse , Motshosi Patience , Zuze Boitumelo , Makhema Joseph , Musonda Rosemary M. , Otukile Dimpho , Modongo Chawangwa , Kgwaadira Botshelo T. , Fane Keabetswe , Gaseitsiwe Simani , Warren Rob M. , Moyo Sikhulile , Dippenaar Anzaan , Streicher Elizabeth M. 
Published: February 2025

BackgroundThe emergence of drug-resistant Mycobacterium tuberculosis (M. tb) strains remains a threat to tuberculosis (TB) prevention and care. Understanding the drug resistance profiles of circulating strains is crucial for effective TB control. This study aimed to describe the genetic diversity of rifampicin-resistant M. tb strains circulating in Botswana using whole genome sequencing (WGS).MethodsThis study included 202 stored M. tb isolates from people diagnosed with rifampicin-resistant TB (RR-TB) between January 2016 and June 2023. Genomic DNA was extracted using the cetyltrimethylammonium bromide (CTAB) method. Library preparation was performed using the Illumina DNA prep kit following the manufacturer's instructions. Sequencing was done on Illumina NextSeq2000. TBProfiler software was used to identify known M. tb lineages and drug resistance profiles. Statistical analyses were performed on STATA version 18.ResultsWGS analysis revealed multidrug resistance (57.9%: 95% CI; 50.7–64.8), Pre-XDR (16.8%, 95% CI: 11.9–22.7), RR-TB (20.2%: 95% CI: 14.98–26.5), and HR-TB (0.5%, 95% CI; 0.01–2.7). We identified a high genetic diversity with three predominant lineages: lineage 4 (60.9%, 95% CI; 53.8–67.7), lineage 1 (22.8%: 95% CI; 17.2–29.2), and lineage 2 (13.9%, 95% CI: 9.4–19.4). The most frequently observed drug resistance mutations for rifampicin, isoniazid, ethambutol, streptomycin, pyrazinamide, and fluoroquinolones were rpoB S450L (28.6%), katG S315T (60.5%), embA_c.-29_-28delCT, embB Q497R (31.7%), rrs_n.517C&gt;T (47.1%), pncA_c.375_389delCGATGAGGTCGATGT (36.0%) and gyrA A90V (79.4%), respectively. No bedaquiline and delamanid resistance-associated mutations were detected.ConclusionsThis study highlights the high genetic diversity of M. tb strains, with a predominance of lineage 4 among people with RR-TB in Botswana. It provides valuable insights into the genetic diversity of rifampicin-resistant M. tb strains circulating in Botswana.
IL-6/GATA2/SERPINE1 pathway is implicated in regulating cellular senescence after acute kidney injury
Authors: Su Hongshuang , Lin Xiaoxi , Paredong Ayinuer , Yao Congcong , Zhang Yan , Geng Mengke , Guan Yuqian , Gong Lichao , Jiang Feng , Lv Qi , Shou Songtao , Jin Heng 
Published: February 2025

PurposeAcute kidney injury (AKI) secondary to Rhabdomyolysis syndrome represents a life-threatening complication, characterized by notably high incidence and mortality rates. The role of cellular senescence in the progression of AKI has increasingly garnered attention in recent years. Our previous research has demonstrated that remote ischemic postconditioning (RIPC) can attenuate renal cellular senescence and elevation of serum level of interleukin-6 (IL-6) induced by ischemia-reperfusion injury following crush injury. The objective of this study is to investigate the specific role of IL-6 in Rhabdomyolysis-induced AKI (RM-AKI).MethodsWe established a mouse model of RM-AKI by intramuscular injection of glycerol and simulated RM-AKI at the cellular level by treating Hk-2 cells with myoglobin. Tocilizumab (TCZ), a humanized monoclonal antibody against the interleukin-6 (IL-6) receptor, is a key substance. IL-6, a multifunctional cytokine, plays a crucial role in the occurrence and development of various kidney diseases. It can promote inflammatory responses, cell proliferation, fibrosis, and other processes. TCZ exerts a protective effect on the kidneys by specifically binding to the IL-6 receptor and blocking the signal transduction of IL-6. Additionally, the levels of IL-6 were detected by employing ELISA kits. RNA sequencing analysis was performed on cells treated with myoglobin and tocilizumab. Flow cytometry was utilized to assess cell cycle distribution and the percentage of senescent cells. The expression levels of SERPINE1, GATA2, p53, and p21 were determined by real-time quantitative PCR and Western blot. Additionally, a dual-luciferase reporter gene assay was conducted to validate the binding effect of SERPINE1 and GATA2.ResultsTranscriptome Analysis revealed that genes including GATA2 and SERPINE1 were downregulated in HK-2 cells following tocilizumab treatment. Inhibition of the IL-6 receptor by tocilizumab in these cells led to a reduction in cellular senescence, accompanied by decreased of the cell cycle regulatory proteins P53 and P21 in mRNA and protein levels, while alleviating cell cycle arrest. Additionally, a dual-luciferase reporter assay confirmed that GATA2 binds to the promoter of SERPINE1 (PAI-1), thereby initiating its transcription.ConclusionThe IL-6/GATA2/SERPINE1 pathway mediates cellular senescence after acute kidney injury, and inhibiting IL-6 can alleviate AKI-induced cellular senescence, providing an important basis for exploring new therapeutic strategies.
Bidirectional relationship between depression and activities of daily living and longitudinal mediation of cognitive function in patients with Parkinson’s disease
Authors: Xu Yue , Chen Durong , Dong Meiqi , Zhang Yun , Yu Hongmei , Han Yanqing 
Published: February 2025

ObjectiveTo investigate the bidirectional relationship between depression and activities of daily living (ADL) in Parkinson’s disease (PD) patients and explore the mediating role of cognitive function over time.MethodsData from 892 PD patients from the Parkinson’s Progression Markers Initiative (PPMI) database were included in this study, and depression, cognitive function, and ADL were measured using the Geriatric Depression Scale (GDS-15), Montreal Cognitive Assessment Scale (MoCA), and Unified Parkinson’s Disease Rating Scale, Part II (UPDRS II) respectively. The cross-lagged panel model (CLPM) was employed to analyze the reciprocal relationship between depression and ADL. Then, we explored the mediating role of cognitive function in the bidirectional relationship between depression and ADL in patients with PD, and the mediation effect test was carried out using a bias-corrected nonparametric percentile bootstrap approach.ResultsDepression in patients with PD predicted their subsequent ADL (β = 0.079, p &lt; 0.01), and ADL also predicted their subsequent depression (β = 0.069, p &lt; 0.05), In addition, Bootstrap analysis showed that cognitive function played a significant mediating role in prediction of depression to ADL in patients with PD (β = 0.006, p = 0.074, 95%CI = 0.001 ~ 0.014), and cognitive function also played a significant mediating role in prediction of depression to ADL (β = 0.006, p = 0.067, 95%CI = 0.001 ~ 0.013).ConclusionThere is a bidirectional relationship between depression and ADL in patients with PD. Furthermore, we found that cognitive function mediates the relationship that exists between depression and ADL in patients with PD. Interventions aimed at enhancing cognitive function could potentially lessen the vicious cycle of depression and ADL in PD, thus improving patient quality of life (QOL).
Quantification and correlation of amyloid-β plaque load, glial activation, GABAergic interneuron numbers, and cognitive decline in the young TgF344-AD rat model of Alzheimer’s disease
Authors: Futácsi Anett , Rusznák Kitti , Szarka Gergely , Völgyi Béla , Wiborg Ove , Czéh Boldizsár 
Published: February 2025

BackgroundAnimal models of Alzheimer’s disease (AD) are essential tools for investigating disease pathophysiology and conducting preclinical drug testing. In this study, we examined neuronal and glial alterations in the hippocampus and medial prefrontal cortex (mPFC) of young TgF344-AD rats and correlated these changes with cognitive decline and amyloid-β plaque load.MethodsWe compared TgF344-AD and non-transgenic littermate rats aged 7–8 months of age. We systematically quantified β-amyloid plaques, astrocytes, microglia, four different subtypes of GABAergic interneurons (calretinin-, cholecystokinin-, parvalbumin-, and somatostatin-positive neurons), and newly generated neurons in the hippocampus. Spatial learning and memory were assessed using the Barnes maze test.ResultsYoung TgF344-AD rats had a large number of amyloid plaques in both the hippocampus and mPFC, together with a pronounced increase in microglial cell numbers. Astrocytic activation was significant in the mPFC. Cholecystokinin-positive cell numbers were decreased in the hippocampus of transgenic rats, but calretinin-, parvalbumin-, and somatostatin-positive cell numbers were not altered. Adult neurogenesis was not affected by genotype. TgF344-AD rats had spatial learning and memory impairments, but this cognitive deficit did not correlate with amyloid plaque number or cellular changes in the brain. In the hippocampus, amyloid plaque numbers were negatively correlated with cholecystokinin-positive neuron and microglial cell numbers. In the mPFC, amyloid plaque number was negatively correlated with the number of astrocytes.ConclusionPronounced neuropathological changes were found in the hippocampus and mPFC of young TgF344-AD rats, including the loss of hippocampal cholecystokinin-positive interneurons. Some of these neuropathological changes were negatively correlated with amyloid-β plaque load, but not with cognitive impairment.
Prediction models for cognitive impairment in middle-aged patients with cerebral small vessel disease
Authors: Zheng Wei , Qin Xiaoyan , Mu Ronghua , Yang Peng , Huang Bingqin , Song Zhixuan , Zhu Xiqi 
Published: February 2025

PurposeThis study aims to develop hippocampal texture model for predicting cognitive impairment in middle-aged patients with cerebral small vessel disease (CSVD).MethodsThe dataset included 145 CSVD patients (Age, 52.662 ± 5.151) and 99 control subjects (Age, 52.576±4.885). An Unet-based deep learning neural network model was developed to automate the segmentation of the hippocampus. Features were extracted for each subject, and the least absolute shrinkage and selection operator (LASSO) method was used to select radiomic features. This study also included the extraction of total intracranial volume, gray matter, white matter, cerebrospinal fluid, white matter hypertensit, and hippocampus volume. The performance of the models was assessed using the areas under the receiver operating characteristic curves (AUCs). Additionally, decision curve analysis (DCA) was conducted to justify the clinical relevance of the study, and the DeLong test was utilized to compare the areas under two correlated receiver operating characteristic (ROC) curves.ResultsNine texture features of the hippocampus were selected to construct radiomics model. The AUC values of the brain volume, radiomics, and combined models in the test set were 0.593, 0.843, and 0.817, respectively. The combination model of imaging markers and hippocampal texture did not yield improved a better diagnosis compared to the individual model (p &gt; 0.05).ConclusionThe hippocampal texture model is a surrogate imaging marker for predicting cognitive impairment in middle-aged CSVD patients.
Behavioral representations within the endogenous dual attentional pathways during audiovisual integration processing
Authors: Guan Zhongtian , Yan Mingli , He Miao , Liu Yubo , Zhang Zhixi , Li Chunlin 
Published: February 2025

IntroductionAudiovisual integration processes are modulated by top-down attention and may involve different neural mechanisms under spatial, temporal, and neutral properties, which are externally manifested by subjects adopting different cognitive strategies. Composite behavioral indicators are able to assess the balance between speed and accuracy when subjects perform a task, thus further revealing behavioral representations of cognitive tasks. However, the cognitive strategies and neural mechanisms involved in audiovisual integration under endogenous attentional modulation are unclear, and in particular, the functional relationship between the dorsal and ventral pathways still needs to be thoroughly investigated.MethodsWe design only auditory (A), only visual (V), and audiovisual attention (VA) tasks based on the classical Posner paradigm with spatial, temporal and neutral cues for behavioral indicators, brain activation, and their correlations.ResultsOur results showed significant differences in behavioral performance between tasks, with weaker performance on the dual-channel task than on the single-channel task. The brain showed consistent activation in the frontal eye field, inferior parietal lobule, supplementary motor area, superior temporal gyrus, middle occipital gyrus and cuneus. The dorsal pathway is mainly associated with spatial processing and executive control, while the ventral pathway is involved in object recognition and semantic processing. In correlation analyses, proportions of correct responses (PC) showed a wider range of results. Spatio-temporal attention mobilized more cognitive resources than neutral attention in the audiovisual task and influenced execution strategies. Inverse efficiency score (IES) revealed endogenous attentional modulation of energy expenditure in the dual-channel task, whereas rate-correct score (RCS) revealed inter-task differences in correct response efficiency. Linear integrated speed–accuracy score (LISAS) and balanced integration score (BIS) showed different speed-accuracy balance in our task.ConclusionOur findings emphasize the synergy of functions and the dynamic synergy of cognitive processes in dorsal and ventral attentional pathways, which contribute to the management of cognitive flexibility and efficiency.
Disproportionality analysis of upadacitinib-related adverse events in inflammatory bowel disease using the FDA adverse event reporting system
Authors: Wang Shiyi , Wang Xiaojian , Ding Jing , Zhang Xudong , Zhu Hongmei , Fan Yihong , Sun Changbo 
Published: February 2025

BackgroundUpadacitinib, a Janus kinase inhibitor, has been increasingly used over the past few years to treat moderate to severe ulcerative colitis and Crohn’s disease in patients who are insufficiently responsive or intolerant to tumor necrosis factor (TNF) antibodies, demonstrating notable clinical efficacy. The long-term safety of upadacitinib in extensive populations remains unexplored. This study evaluates upadacitinib-related adverse events (AEs) utilizing data from the US Food and Drug Administration Adverse Event Reporting System (FAERS).MethodsWe employed disproportionality analyses, including the proportional reporting ratio (PRR), reporting odds ratio (ROR), Bayesian confidence propagation neural network (BCPNN), and empirical Bayesian geometric mean (EBGM) algorithms to identify signals of upadacitinib-associated AEs for treating inflammatory bowel disease (IBD).ResultsFrom a total of 7,037,004 adverse event reports sourced from the FAERS database, 37,822 identified upadacitinib as the primary suspect drug in adverse drug events (ADEs), including 1,917 reports specifically related to the treatment of inflammatory bowel disease (IBD). The most commonly reported AEs were acne, product residue present, haematochezia, frequent bowel movements, flatulence, blood cholesterol increased, aligning with clinical trial outcomes. Notably, significant but unexpected AEs, such as rosacea, proctalgia, polyp, were also reported. Subgroup analysis indicated that the most prevalent AEs among the elderly included pulmonary embolism, cataract, and sepsis, whereas the 18–65 age group most frequently reported acne, abdominal pain, and nasopharyngitis. The median onset time for AEs related to upadacitinib was 41.00 days (interquartile range [IQR] 10–141.5 days), with the majority occurring within 3 months of treatment initiation (n = 269, 66.09%), particularly in the first month (n = 171, 42.01%).ConclusionOur findings affirm clinical observations and reveal potential new AE signals for upadacitinib, underscoring the need for prospective clinical studies to verify these results and clarify their clinical relevance. This study contributes valuable evidence for ongoing safety evaluations of upadacitinib.
Post-treatment of rat aflatoxicosis by camel milk and silymarin
Authors: Hassaneen Nahla H. , Hemeda Shabaan A. , El Nahas Abeer F. , Albadrani Ghadeer M. , Al-Ghadi Muath Q. , Mohammedsaleh Zuhair M. , Fadl Sabreen E. , El-Diasty Eman M. , Sakr Hader I. 
Published: February 2025

BackgroundAflatoxins are highly potent mycotoxins that can seriously harm the health of humans and a variety of animal species. On the other hand, camel milk and silymarin offer a variety of positive effects for many animal species. In addition, camel milk and silymarin reduce the impact of AFB1 on the hematology, serum biochemical markers, histopathology of the liver and testes, and expression of the inflammatory, antioxidant, and male reproductive genes.Methods40 rats were used to evaluate the beneficial effect of silymarin and camel milk against aflatoxin B1 (AFB1) toxicity in rats. The classified treatments were the control negative (no treatment) and the control positive (supplied with 1.4 mg aflatoxin/kg diet) for 28 days. Camel milk group (supplied with 1.4 mg aflatoxin/kg diet) for 28 days and camel milk (1 milliliter of camel milk per kilogram of body weight) orally, from day 29 to day 43). Silymarin (supplied with 1.4 mg aflatoxin/kg diet) for 28 days and silymarin (20 mg silymarin/kg b.wt), orally, from day 29 to day 43). The evaluation was done through measuring leukocyte count, liver function tests, carcinoembryonic antigen (CEA), alpha-fetoprotein (AFP), ferritin, and testosterone. Moreover, the histopathology of the liver and testes was done along with expression levels of specific genes in the liver and testes.ResultsThe outcomes showed that the post-treatment with silymarin and camel milk improved biochemical markers in serum and ability to reproduce.ConclusionIn conclusion, post-treatment with camel milk and silymarin could mitigate the negative effect of AFB1 on rats.
Future anxiety and the motives for postponing parenthood: generational time perspective and life satisfaction as mediators
Authors: Szcześniak Małgorzata , Timoszyk-Tomczak Celina , Łoś Julia , Grzeczka Monika 
Published: February 2025

IntroductionResearch to date has focused largely on the consequences of delayed parenting. However, little is known about the reasons and relevant mechanisms that are involved in people’s decisions to delay parenthood. The aim of our study was to verify how anxiety about the future relates to the motives for deferred parenthood and how this relationship is mediated by generational time perspective and life satisfaction.MethodsA total of 203 Polish adults between 18 and 40 years of age participated in the study. All of them were of reproductive age but did not yet have children. Respondents completed the following questionnaires: The Dark Future Scale, The Multidimensional Scale of Motives for Postponing Parenthood, The Generational Time Perspective Questionnaire, and The Riverside Life Satisfaction Scale.ResultsThe results obtained in the study show that future anxiety correlates significantly and positively with all six motives for postponing parenthood, postponed parenthood overall, and generational affectivity. It is also associated with the generational cognitive perspective at the level of tendency, and negatively with life satisfaction. According to our findings, in all seven models, at least one of the factors mediated the relationship between future anxiety and motives for postponing parenthood/its total score.ConclusionThe current study advances the understanding of how the subjective future time perspective is related to delayed parenthood through generational concern and reduced life satisfaction. Our findings may indicate that despite the importance of sociodemographic variables in postponing parenthood (e.g., lack of housing, financial instability, acquiring knowledge, education, etc.), variables related to personality and time perspective play a very important role in postponing the decision to have a child.
The multiple self and psychological openness
Authors: Suszek Hubert , Kopera Maciej , Jakubczyk Andrzej 
Published: February 2025

IntroductionThis research identifies and explores two distinct modes of self-experience and their influence on psychological openness. We distinguish between the unitary self-mode, where individuals perceive themselves as cohesive, stable entities, and the multiple self-mode, where they recognize their diverse, context-dependent aspects. These modes represent fundamentally different ways of experiencing and organizing self-knowledge that can be situationally activated. While both modes of self-experience have been theoretically described, their influence on psychological functioning remains empirically unexplored.MethodsThrough five experiments (N = 989), we tested whether activation of the multiple self-mode increases psychological openness compared to activation of the unitary self-mode using different experimental manipulations and measures.ResultsInduction of the multiple self enhanced psychological openness compared to induction of the unitary self. This effect was consistently observed across various domains of openness: openness as a state (Study 1, N = 204), openness to change (Studies 3 and 4, N = 230 and N = 184), range of values (Studies 2 and 3, N = 212 and N = 230), psychological mindedness and decentering (Study 5, N = 159). Results consistently showed moderate effect sizes (d = 0.31–0.44) across different operationalizations of both the multiple self-induction and openness measures.DiscussionThese findings indicate that the way in which individuals organize their self-knowledge has important implications for their cognitive and experiential flexibility, contributing to our understanding of personality plasticity and development.