bluuebunny/crossref_metadata_2025_split huggingface dataset:
Association of dementia with the 28-day mortality of sepsis: an observational and Mendelian randomization study
Authors: Lan Ying , Zhu Junchen , Pu Peng , Ni Wentao , Yang Qilin , Chen Lvlin 
Published: November 2024

BackgroundObservational research suggests that individuals with dementia who have sepsis face a higher likelihood of death. However, whether there is a causal relationship between the two remains unknown.MethodsWe analyzed data from patients diagnosed with sepsis and dementia, extracted from the Medical Information Mart for Intensive Care IV (MIMIC-IV) database. To examine the correlation between dementia and 28-day mortality in sepsis, we utilized Cox proportional hazards models. Following this, we performed a Mendelian randomization (MR) study with two samples to investigate the potential link between dementia and mortality within 28 days in sepsis.ResultsThis study included a total of 22,189 patients diagnosed with sepsis, among whom 1,346 cases (6.1%) had dementia. After adjusting for multiple confounding factors, dementia was associated with an increased risk of 28-day mortality in sepsis (HR = 1.25, 95% CI = 1.12–1.39, p &lt; 0.001). In the MR analysis, there appeared to be a causal relationship between genetically predicted dementia with Lewy bodies (DLB) (OR = 1.093, 95% CI = 1.016–1.177, p = 0.017) and 28-day mortality in sepsis. However, there was no evidence of causality between any dementia (OR = 1.063, 95% CI = 0.91–1.243, p = 0.437), Alzheimer’s disease (AD) (OR = 1.126, 95% CI = 0.976–1.299, p = 0.103), vascular dementia (VD) (OR = 1.008, 95% CI = 0.93–1.091, p = 0.844), and the risk of 28-day mortality in sepsis.ConclusionIn the observational analysis, dementia was associated with an increased risk of 28-day mortality in septic patients. However, in the MR analysis, only DLB was associated with increased 28-day mortality in septic patients, with no observed correlation for other dementia subtypes.
The novel estrogen receptor beta agonist EGX358 and APOE genotype influence memory, vasomotor, and anxiety outcomes in an Alzheimer’s mouse model
Authors: Schwabe M. R. , Fleischer A. W. , Kuehn R. K. , Chaudhury S. , York J. M. , Sem D. S. , Donaldson W. A. , LaDu M. J. , Frick K. M. 
Published: November 2024

IntroductionAlzheimer’s disease (AD) prevalence and severity are associated with increased age, female sex, and apolipoprotein E4 (APOE4) genotype. Although estrogen therapy (ET) effectively reduces symptoms of menopause including hot flashes and anxiety, and can reduce dementia risk, it is associated with increased risks of breast and uterine cancer due to estrogen receptor alpha (ERα)-mediated increases in cancer cell proliferation. Because ERβ activation reduces this cell proliferation, selective targeting of ERβ may provide a safer method of improving memory and reducing hot flashes in menopausal women, including those with AD. APOE genotype influences the response to ET, although it is unknown whether effects of ERβ activation vary by genotype.MethodsHere, we tested the ability of long-term oral treatment with a novel highly selective ERβ agonist, EGX358, to enhance object recognition and spatial recognition memory, reduce drug-induced hot flashes, and influence anxiety-like behaviors in female mice expressing 5 familial AD mutations (5xFAD-Tg) and human APOE3 (E3FAD) or APOE3 and APOE4 (E3/4FAD). Mice were ovariectomized at 5 months of age and were then treated orally with vehicle (DMSO) or EGX358 (10 mg/kg/day) via hydrogel for 8 weeks. Spatial and object recognition memory were tested in object placement (OP) and object recognition (OR) tasks, respectively, and anxiety-like behaviors were tested in the open field (OF) and elevated plus maze (EPM). Hot flash-like symptoms (change in tail skin temperature) were measured following injection of the neurokinin receptor agonist senktide (0.5 mg/kg).ResultsEGX358 enhanced object recognition memory in E3FAD and E3/4FAD mice but did not affect spatial recognition memory. EGX358 also reduced senktide-induced tail temperature elevations in E3FAD, but not E3/4FAD, females. EGX358 did not influence anxiety-like behaviors or body weight.DiscussionThese data indicate that highly selective ERβ agonism can facilitate object recognition memory in both APOE3 homozygotes and APOE3/4 heterozygotes, but only reduce the magnitude of a drug-induced hot flash in APOE3 homozygotes, suggesting that APOE4 genotype may blunt the beneficial effects of ET on hot flashes. Collectively, these data suggest a potentially beneficial effect of selective ERβ agonism for memory and hot flashes in females with AD-like pathology, but that APOE genotype plays an important role in responsiveness.
Causal associations of ischemic stroke, metabolic factors, and related medications with epilepsy: a Mendelian randomization study
Authors: Wang Wencai , Liu Menghao , Liu Fengling , Wang Zun , Ye Wei , Li Xianfeng 
Published: November 2024

BackgroundEarlier researches have demonstrated that ischemic stroke, metabolic factors, and associated medications may influence the risk of epilepsy. Nevertheless, the causality between these elements and epilepsy remains inconclusive. This study aims to examine whether ischemic stroke, metabolic factors, and related medications affect the overall risk of epilepsy.MethodsWe used single nucleotide polymorphisms associated with ischemic stroke, hypothyroidism, hypertension, blood glucose levels, high cholesterol, serum 25-Hydroxyvitamin D levels, testosterone, HMG CoA reductase inhibitors, and beta-blocking agents as instrumental variables in a Mendelian randomization technique to investigate causality with epilepsy. Multiple sensitivity methods were performed to evaluate pleiotropy and heterogeneity.ResultsThe IVW analysis revealed positive associations between ischemic stroke (OR = 1.29; p = 0.020), hypothyroidism (OR = 1.05; p = 0.048), high blood pressure (OR = 1.10; p = 0.028), high cholesterol (OR = 1.10; p = 0.024), HMG CoA reductase inhibitors (OR = 1.19; p = 0.003), beta-blocking agents (OR = 1.20; p = 0.006), and the risk of epilepsy. Conversely, blood glucose levels (OR = 0.79; p = 0.009), serum 25-Hydroxyvitamin D levels (OR = 0.75; p = 0.020), and testosterone (OR = 0.62; p = 0.019) exhibited negative associations with the risk of epilepsy. Sensitivity analyses confirmed the robustness of these findings (p &gt; 0.05).ConclusionOur research suggests that ischemic stroke, hypothyroidism, high blood pressure, high cholesterol, HMG CoA reductase inhibitors, and beta-blockers may increase the risk of epilepsy, whereas serum 25-Hydroxyvitamin D levels and blood glucose levels may reduce the risk.
Association between platelet-to-high-density lipoprotein cholesterol ratio and future stroke risk: a national cohort study based on CHARLS
Authors: Hou Xin , Zhu Meibao , Zhu Zhenghao , Li Yanhui , Chen Xinmin , Zhang Xiaohong 
Published: November 2024

BackgroundAccording to recent research, there is a considerable correlation between the severity of coronary artery disease and the platelet-to-high-density lipoprotein cholesterol ratio (PHR), which suggests that PHR is a potentially valuable inflammatory biomarker. However, the body of current research offers insufficiently strong evidence to clarify the connection between PHR and the incidence of stroke. Therefore, this study aims to elucidate any potential associations between PHR and stroke risk.MethodsThis study employed data from the China Health and Retirement Longitudinal Study (CHARLS) covering the period from 2011 to 2018. It included 5,872 participants who did not have a history of stroke in 2011. These patients were separated into four groups according to their baseline PHR quartiles. The main goal of the study was to focus on stroke outcomes. Stroke was defined as an occurrence of a cerebrovascular accident confirmed by a physician. We employed Cox proportional hazards regression models to investigate the association between PHR and the likelihood of experiencing a stroke. Furthermore, we conducted restricted cubic spline regression analysis and subgroup analysis.ResultsThe average follow-up period was 77.5 months, during which 390 participants experienced a stroke. In comparison to the lowest quartile group, participants in the highest quartile of PHR had a 49% increased risk of stroke (HR 1.49, 95% CI 1.13–1.96, p = 0.004). The adjusted multivariable Cox regression analysis maintained the statistical significance of this association (aHR 1.42, 95% CI 1.06–1.90, p = 0.019). After adjustment, a positive linear relationship between stroke risk and PHR was identified through restricted cubic spline regression analysis (nonlinear p &gt; 0.05). Additionally, the impact of stroke was consistent across a variety of subgroups, as evidenced by subgroup analysis.ConclusionOur study indicates that higher PHR levels are significantly associated with an increased risk of stroke and that these levels can be used to identify groups that are at high risk of stroke.
Impact of sports vision training on visuomotor skills and shooting performance in elite skeet shooters
Authors: Guo Yuqiang , Yuan Tinggang , Peng Jian , Deng Liwei , Chen Chao 
Published: November 2024

IntroductionVision serves as a critical channel for athletes to acquire information during competitions and constitutes a vital component of their competitive ability. Through scientifically designed sports visual training, specific visual skills can be enhanced, thereby assisting athletes in achieving optimal performance in competitive settings. This study aim to explore the visuomotor abilities and shooting performance of skeet shooters through Sports Vision Training (SVT).MethodsTwenty elite skeet shooters were recruited and randomly assigned to an experimental group (EXP, n = 10) and a control group (CON, n = 10). The EXP underwent 6-week of SVT on Senaptec Seneory Station, twice a week, while the CON completed an equivalent workload of target-tracking training.ResultVisuomotor skills testing showed significant improvements in Near- Far Quickness, Perception Span, and Eye-hand Coordination in the EXP (p &lt; 0.05), with no changes in the CON. Comparative post-test results between the two groups showed significant differences in N/F Q, Target Capture, Perception Span, Eye-hand Coordination, and Go/ No Go (p &lt; 0.05). In shooting performance indicators, EXP shooters showed a highly significant improvement in hit accuracy (p &lt; 0.01), with a similar difference compared to the CON. Additionally, they exhibited a highly significant improvement in shotgun-mounting reaction time (p &lt; 0.01). Kinematic indicators of shotgun movement during the firing process for shot 2 showed significant differences in peak velocity (p &lt; 0.01), X-axis (p = 0.033) and Y-axis (p = 0.001) displacement.ConclusionSVT can enhance visuomotor abilities in skeet shooters and has a positive impact on their shooting technique. This is primarily manifested in shorter shotgun-mounting reaction time and improved efficiency in action at shot 2, effectively improving their shooting accuracy.
Eye movement characteristics of emotional face recognizing task in patients with mild to moderate depression
Authors: Yang Qian , Fu Yanyan , Yang Qiuli , Yin Dongqing , Zhao Yanan , Wang Hao , Zhang Han , Sun Yanran , Xie Xinyi , Du Jian 
Published: November 2024

ObjectiveDepression is a complex affective disorder characterized by high prevalence and severe impact, commonly presenting with cognitive impairment. The objective diagnosis of depression lacks precise standards. This study investigates eye movement characteristics during emotional face recognition task (EFRT) in depressive patients to provide empirical support for objective diagnosis.MethodsWe recruited 43 patients with depression (Depressive patients, DP) from a psychiatric hospital and 44 healthy participants (Healthy Control, HC) online. All participants completed an EFRT comprising 120 trials. Each trial presented a gray screen for 800 ms followed by a stimulus image for judgment. Emotions were categorized as positive, neutral, or negative. Eye movement trajectories were recorded throughout the task. Latency of First Fixation (LFF), Latency of First Fixation for Eye AOI, and Latency of First Fixation for Mouth AOI were used as representative indicators of early attention, Proportion of Eye AOI, and Proportion of Mouth AOI as measures of intermediate attention, Accuracy (ACC) and Reaction Time (RT) as behavioral indicators of late-stage attention. In this study, these metrics were employed to explore the differences between patients with depression and healthy individuals.ResultsCompared to healthy participants, individuals with depression exhibit longer first fixation latencies on the eyes and mouth during the early attention stage of emotional face recognition, indicating an avoidance tendency toward key facial recognition cues. In the mid-to-late attention stages, depressive individuals show an increased fixation ratio on the eyes and a decreased fixation ratio on the mouth, along with lower accuracy and longer response times. These findings suggest that, relative to healthy individuals, individuals with depression have deficits in facial recognition.ConclusionThis study identified distinct attention patterns and cognitive deficits in emotional face recognition among individuals with depression compared to healthy individuals, providing an attention-based approach for exploring potential clinical diagnostic markers for depression.
Low-dose trimethoprim-sulfamethoxazole treatment for Pneumocystis pneumonia: a systematic review and meta-analysis
Authors: Huang Hui-Bin , Zhu Yi-Bing , Yu Da-Xing 
Published: November 2024

BackgroundThe recommended standard treatment for Pneumocystis jirovecii pneumonia (PJP) is high-dose trimethoprim-sulfamethoxazole (TMP-SMX) (15–20 mg/kg/d TMP). However, the standard regimen may cause a high incidence of dose-related adverse events (AEs). Therefore, we aimed to conduct a systematic review and meta-analysis to evaluate the efficacy and safety of low-dose TMP-SMX regimens (&lt;15 mg/kg/d of TMP) compared with the standard regimen in patients with PJP.MethodsWe searched PubMed, Embase, and the Cochrane database for relevant articles from inception to 10 March 2024. Studies were included if they focused on PJP patients receiving a low-dose TMP-SMX regimen compared with a standard regimen. The primary outcome was mortality. We assessed study quality and performed subgroup analysis and sensitivity analysis to explore potential heterogeneity among the included studies.ResultsSeven studies were included. Overall, the low-dose regimen significantly reduced the risk of mortality (odds ratio [OR] = 0.49; 95% CI, 0.30–0.80; I2 = 16%; P = 004). This finding was confirmed in further sensitivity and subgroup analyses. The low-dose regimen also significantly reduced total AEs (OR = 0.43; 95% CI, 0.29–0.62; I2 = 0%; P &lt; 0.0001), and improved the incidence of most specific AEs (ORs ranged from 0.13 to 0.89). In addition, the low-dose regimen had significantly more patients completing the initial regimen (P = 0.002), fewer patients requiring dose reductions (P = 0.04), and almost significantly fewer patients requiring a switch to a second-line regimen (P = 0.06).ConclusionThe limited available evidence suggests that a low-dose TMP-SMX regimen significantly reduced mortality and total AEs in PJP patients. Thus, it is one of the potentially promising therapies to PJP and more high-quality and multi-center randomized trials should be conducted in the future.
Risks of malignancies related to disease-modifying antirheumatic drugs in rheumatoid arthritis: a pharmacovigilance analysis using the FAERS database
Authors: Xiong Wan , Li Yilin , Hu Lin , He Gefei , Huang Juanjuan 
Published: November 2024

ObjectivesOver the years when disease-modifying antirheumatic drugs (DMARDs) have been used in rheumatoid arthritis patients, reports of malignancies have emerged. This study aims to investigate the association between malignancies and DMARDs by using data extracted from the Food and Drug Administration Adverse Event Reporting System (FAERS).MethodsFAERS data (January 2019 to December 2023) were reviewed. For each drug-event pair, the disproportionality analysis was conducted to evaluate the risk of malignancy. Multivariate logistic regression was implemented to mitigate potential biases. Moreover, the time to onset of malignancy was also evaluated.ResultsWe conducted a detailed search for rheumatoid arthritis indications and identified a total of 17,412 adverse event reports associated with malignancies, with selective DMARDs designated as the role code “primary suspect”. At the preferred term level, there were 198 positive signals, among which the lower limit of the 95% confidence interval for the information component is 3.55 for squamous cell carcinoma of the skin, 2.39 for breast cancer, and 2.27 for lymphoproliferative disorder. In comparison to other DMARDs, targeted synthetic DMARDs were associated with a broader range of malignancies at both preferred term and Standardized MedDRA Queries levels. The number of adverse events reported in female patients is approximately 2–3 times higher than men, and the median age across the population was approximately 62 years. In terms of onset time, the conventional synthetic DMRADs exhibited a relatively longer median time, ranging from 3.58 to 7.08 years, while the targeted synthetic DMARDs demonstrated a shorter median time of 0.83–1.67 years.ConclusionOur study uncovers varying degrees of malignancy risks related to DMARDs, with a significantly higher risk observed in targeted synthetic DMARDs. Additionally, novel malignancy signals, not documented in product labels, have been detected. In the future, further research will be necessary to validate our findings.
First transcriptome analysis of the venom glands of the scorpion Hottentotta zagrosensis (Scorpions: Buthidae) with focus on venom lipolysis activating peptides
Authors: Salabi Fatemeh , Jafari Hedieh , Mahdavinia Masoud , Azadnasab Reza , Shariati Saeedeh , Baghal Mahsa Lari , Tebianian Majid , Baradaran Masoumeh 
Published: November 2024

IntroductionScorpion venom is a rich source of biological active peptides and proteins. Transcriptome analysis of the venom gland provides detailed insights about peptide and protein venom components. Following the transcriptome analysis of different species in our previous studies, our research team has focused on the Hottentotta zagrosensis as one of the endemic scorpions of Iran to obtain information about its venom proteins, in order to develop biological research focusing on medicinal applications of scorpion venom components and antivenom production. To gain insights into the protein composition of this scorpion venom, we performed transcriptomic analysis.MethodsTranscriptomic analysis of the venom gland of H. zagrosensis, prepared from the Khuzestan province, was performed through Illumina paired-end sequencing (RNA-Seq), Trinity de novo assembly, CD-Hit-EST clustering, and annotation of identified primary structures using bioinformatics approaches.ResultsTranscriptome analysis showed the presence of 96.4% of complete arthropod BUSCOs, indicating a high-quality assembly. From total of 45,795,108 paired-end 150 bp trimmed reads, the clustering step resulted in the generation of 101,180 de novo assembled transcripts with N50 size of 1,149 bp. 96,071 Unigenes and 131,235 transcripts had a significant similarity (E-value 1e-3) with known proteins from UniProt, Swissprot, Animal toxin annotation project, and the Pfam database. The results were validated using InterProScan. These mainly correspond to ion channel inhibitors, metalloproteinases, neurotoxins, protease inhibitors, protease activators, Cysteine-rich secretory proteins, phospholipase A enzymes, antimicrobial peptides, growth factors, lipolysis-activating peptides, hyaluronidase, and, phospholipase D. Our venom gland transcriptomic approach identified several biologically active peptides including five LVP1-alpha and LVP1-beta isoforms, which we named HzLVP1_alpha1, HzLVP1_alpha2, HzLVP1_alpha3, HzLVP1_beta1, and HzLVP1_beta and have extremely characterized here.DiscussionExcept for HzLVP1_beta1, all other identified LVP1s are predicted to be stable proteins (instability index &lt;40). Moreover, all isoform of LVP1s alpha and beta subunits are thermostable, with the most stability for HzLVP1_alpha2 (aliphatic index = 71.38). HzLVP1_alpha2 has also the highest half-life. Three-dimensional structure of all identified proteins compacts with three disulfide bridges. The extra cysteine residue may allow the proteins to form a hetero- or homodimer. LVP1 subunits of H. zagrosensis potentially interact with adipose triglyceride lipase (ATGL) and hormone-sensitive lipase (HSL), two key enzymes in regulation of lipolysis in adipocytes, suggesting pharmacological properties of these identified proteins.
Tracing the historical foundations of infliximab in Crohn’s disease treatment: a cited reference analysis
Authors: Yeung Andy Wai Kan 
Published: November 2024

IntroductionThe use of infliximab to treat Crohn’s disease patients has been evaluated for decades. The current work aimed to identify the historical roots of this research topic.MethodsThe literature database Web of Science Core Collection was searched to identify relevant papers. Cited reference analysis on the identified literature set was performed using CRExplorer, a dedicated bibliometric software. The disruption index was computed with an automated routine described by Leydesdorff and Bornmann, which is freely available online. Based on data from citation count and reference list, the disruption index can range from −1 to +1, with −1 meaning a continuity from existing research and +1 meaning a disruption.ResultsThis analysis successfully identified key references dealing with infliximab use on Crohn’s disease patients, such as the original report that introduced the Crohn’s Disease Activity Index (CDAI) in 1976, the first case series reporting a favourable outcome of infliximab infusion on 10 patients published in 1995, the first randomized controlled trial published in 1997, the ACCENT I and ACCENT II trials published in 1999 and 2002, and a couple of European consensus guidelines on the diagnosis and management of Crohn’s disease.ConclusionCited reference analysis could reveal the historical origins of the use of infliximab in treating Crohn’s disease. Highly cited references included CDAI, important early clinical studies, and European consensus guidelines. The important cited references identified by the analysis provided solid foundation to support subsequent research.