bluuebunny/crossref_metadata_2025_split huggingface dataset:
Association Between Blood Pressure Variation During Dialysis and Cardio‐Cerebrovascular Events
Authors: Fan Zhenliang , Ye Rujia , Yang Qiaorui , Yang Mengfan , Yin Riping , Zhao Dongxue , Fan Junfen , Ma Hongzhen , Shen Yiwei , Xia Hong , Jiang Wenze , Lu Keda 
Published: December 2024

ABSTRACTIn hemodialysis patients, blood pressure variability (BPV) is associated with cardiovascular events and all‐cause mortality. However, previous research has predominantly concentrated on the predialysis BPV. In contrast, intradialytic BPV, reflecting the cardiovascular regulatory function during the process of rapid clearance of volume overload, holds greater relevance to the prognosis of patients. In this study, a latent category trajectory model was used to identify the patterns of intradialytic BPV and analyze the association between intradialytic BPV and the cardio‐cerebrovascular events and other clinical outcomes. We found the variation of intradialytic systolic blood pressure (SBP) was associated with the risk of cardio‐cerebrovascular events in hemodialysis patients. Patients in “SBP Class 4” and “SBP Class 3” subgroups were associated with the occurrence of cardio‐cerebrovascular events and the number of cardio‐cerebrovascular event hospitalizations during the follow‐up period. This indicates that the variation pattern of intradialytic SBP results from the comprehensive action of various BP regulatory mechanisms in the body, which can reflect the level of cardiovascular regulatory function in hemodialysis patients and serve as a predictor of recent adverse cardio‐cerebrovascular events.
Effectiveness and Safety of Using Standardized Treatment Protocols for Hypertension Compared to Usual Care: A Meta‐Analysis of Randomized Clinical Trials
Authors: Satheesh Gautam , Dhurjati Rupasvi , Jha Vivekanand , Schutte Aletta E. , Banigbe Bolanle , Prabhakaran Dorairaj , Moran Andrew E. , Salam Abdul 
Published: December 2024

ABSTRACTLarge gaps persist in the diagnosis, awareness, treatment, and control of hypertension globally. Standardized treatment protocols (STPs) have been widely proposed to guide hypertension treatment, particularly in primary healthcare settings. However, there has been no review that quantifies the effects of hypertension STPs on blood pressure (BP) reduction and control. We conducted a systematic review of randomized clinical trials (RCTs) among adults with hypertension, comparing hypertension STPs (intervention) with usual care (comparator) for effects on BP. Relevant RCTs were identified by searching multiple electronic databases. Random‐effects meta‐analyses were conducted to evaluate between‐group differences in systolic BP reduction (primary outcome), diastolic BP reduction, BP control, and adverse events (AEs). Sixteen RCTs involving 59,945 participants (baseline mean BP: 149/91 mmHg) were included. Reductions in systolic and diastolic BP with STPs compared to usual care were 6.7 (95% CI 3.7–9.8) mmHg and 2.6 (1.2–4.1) mmHg, respectively (p < 0.001 for both). BP control achieved was 57% in the STP group compared to 24% in the usual care group (p < 0.001). The overall incidence of any AEs was 14.5% versus 13.5% (RR 1.27 [0.88–1.82]) with STPs and usual care, respectively. In summary, interventions involving hypertension STPs significantly reduce systolic and diastolic BP and improve BP control compared to usual care. STPs can, therefore, be an efficient strategy to implement evidence‐based treatments and upscale treatment coverage, given the large untreated and uncontrolled hypertension burdens globally.
The kinase LRRK2 is required for the physiological function and expression of the glial glutamate transporter EAAT2 (SLC1A2)
Authors: Di Iacovo Angela , D'Agostino Chiara , Bhatt Manan , Romanazzi Tiziana , Giovannardi Stefano , Cinquetti Raffaella , Roseti Cristina , Bossi Elena 
Published: December 2024

AbstractNeurotransmitter transporters (NTTs) control synaptic responses by modulating the concentration of neurotransmitters at the synaptic cleft. Glutamate is the most abundant excitatory neurotransmitter in the brain and needs to be finely tuned in time and space to maintain a healthy brain and precise neurotransmission. The glutamate transporter EAAT2 (SLC1A2) is primarily responsible for glutamate clearance. EAAT2 impairment has been associated with Alzheimer's disease (AD), Huntington's disease (HD), amyotrophic lateral sclerosis (ALS), and Parkinson's disease (PD). Mutations in leucine‐rich repeat kinase 2 (LRRK2) contribute to both monogenic and sporadic forms of PD, of which the common substitution Gly2019Ser is associated with a significant deficit in EAAT2 expression. The role of pathological mutants of the LRRK2 is intensively studied and reviewed. Here we have focused the attention on the physiological role of LRRK2 on EAAT2, comparing the activity of NTTs with or without the LRRK2 kinase. By heterologous expression in Xenopus laevis oocytes and two‐electrode voltage clamp, the current amplitudes of the selected NTTs and kinetic parameters have been collected in the presence and absence of LRRK2. The results show that EAAT2 expression and function are impaired in the absence of the kinase and also under its pharmacological inhibition via MLi‐2 treatment. LRRK2 stabilizes EAAT2 expression increasing the amount of transporter at the plasma membrane. Interestingly, the LRRK2 action is EAAT2‐specific, as we observed no significant changes in the transport current amplitude and kinetic parameters obtained for the other excitatory and inhibitory NTTs studied. This study, for the first time, demonstrates the physiological importance of LRRK2 in EAAT2 function, highlighting the specificity of LRRK2‐mediated modulation of EAAT2 and suggesting a potential role for the kinase as a checkpoint for preserving neurons from excitotoxicity. In brain conditions associated with impaired glutamate clearance, targeting LRRK2 for EAAT2 regulation may offer novel therapeutic opportunities.image
Identification of Alzheimer's disease susceptibility genes by integrating eight human brain single‐cell transcriptomes with genome‐wide association studies
Authors: He Yijie , Zhu Ping , Gao Shan , Wu Shiyang , Li Xuan , Huang Chen , Chen Yan , Liu Guiyou 
Published: December 2024

AbstractTo date, several studies have integrated genome‐wide association studies (GWAS) and expression quantitative trait loci (eQTL) data from bulk tissues to identify novel Alzheimer's disease (AD) genetic variants and susceptibility genes. However, there is highly cell‐type‐specific nature in different bulk eQTL data. Until now, eQTL data from different brain single cells have been reported. Therefore, integrating eQTL data from different brain single‐cell types along with AD GWAS data makes biological sense for studying the potential biological explanations of AD. Here, we utilized the summary‐data‐based Mendelian randomization (SMR) method to integrate AD GWAS data with eQTL data from eight brain single‐cell types. We identified a larger number of significant genes compared to previous SMR study based on bulk eQTL. Notably, microglia exhibited the highest number of significant genes. Moreover, we conducted validation‐phase SMR analysis, single‐cell analysis, protein–protein interaction (PPI), druggability evaluation, functional enrichment analyses, and colocalization analysis of the top 20 SMR significant genes in microglia. We found that most genes passed the validation and were significantly enriched in microglia. PPI analysis uncovered interactions among PICALM, BIN1, RIN3, CD2AP, CASS4, and MS4A6E. Five most significant SMR genes were further validated through colocalization analysis. RIN3 is the only significant gene across all mentioned analyses and is a novel AD susceptibility gene at the genome‐wide significance level. Druggability evaluation identified KCNQ3, HLA‐DQB1, and RABEP1 as known genes previously targeted for drug development in neurological disorders, suggesting their potential therapeutic relevance in AD.image
Nurses' Perspectives on the Use of Prophylactic Dressings to Prevent Pressure Injury: A Qualitative Study
Authors: McMahon Jake , McInnes Elizabeth , Wan Ching Shan , Straiton Nicola , Lam Louisa , Rodgers Jane , Fulbrook Paul 
Published: December 2024

ABSTRACTAimTo understand, from a nursing perspective, factors affecting the use of prophylactic dressings to prevent pressure injuries in acute hospitalised adults.BackgroundPressure injury causes harm to patients and incurs significant costs to health services. Significant emphasis is placed on their prevention. Relatively recently, prophylactic dressings have been promoted to reduce pressure injury development. However, in the acute care setting, information about the clinical use of these dressing is lacking.DesignQualitative, descriptive.MethodsNineteen medical and surgical nurses participated. Semi‐structured interviews were conducted and transcribed verbatim. Thematic analysis was performed using an inductive approach using NVivo software.ResultsThree themes were identified, reflecting factors that influenced and perpetuated indiscriminate use of prophylactic dressings: False sense of security; Convenience and task prioritisation; and Navigating challenges in evidence‐based pressure injury prevention.ConclusionsThe findings indicate inconsistent prevention practices, with prophylactic dressings often applied without justification or referral to research‐based evidence to guide clinical decision‐making. There was a prevailing attitude of ‘job done’ when a prophylactic dressing was applied.ImpactThis study has identified several factors that perpetuate the inappropriate use of prophylactic dressings for pressure injury prevention that may be amenable to organisational change. The findings indicate that nurses often rely on these dressings as a shortcut due to time constraints, which led to missed skin assessments and low‐value care. The research can be used to inform the development of clear guidelines on dressings within hospital settings which encourage assessment‐based selection for their use, and process‐based guidance for their application, skin surveillance, dressing inspection and removal.Reporting MethodThe Consolidated Criteria for Reporting Qualitative Research (COREQ) reporting guideline was followed.Patient or Public ContributionNeither patients nor the public were directly involved in this study.
Severe bupropion intoxication successfully treated with resin adsorber haemoperfusion
Authors: Wannakittirat Anyarin , Wipattanakitcharoen Aschariya , Tosamran Somjet , Yimsangyad Khanittha , Chaijamorn Weerachai , Lumlertgul Nuttha , Peerapornratana Sadudee , Limotai Chusak , Srisawat Nattachai 
Published: December 2024

AbstractBupropion is used as smoking cessation drug and antidepressant. Drug overdose has multi‐system involvement including neurotoxicity and cardiovascular collapse. Use of haemoperfusion in bupropion toxicity is generally not useful, however in life‐threatening condition it could be a life saver. We reported a case of 30s male with bupropion overdose who ingested 29 tablets of 300‐mg extended‐release bupropion. The patient had status epilepticus with prolonged QTc interval. He remained unconscious with abnormal jerky movements despite multiple high dose antiepileptic drugs. A 4‐h session of resin adsorber haemoperfusion was done with rapid improvement of consciousness within 24 h and seizure control confirmed by electroencephalogram. In severe cases with early presentation, haemoperfusion may be useful to prevent further toxicity.
MtNAD1 associates with the autophagy complex to contribute to the degradation of immunity‐related proteins in Medicago truncatula nodules
Authors: Dong Ru , Wang Weiyun , Luo Na , Li Haoxing , Liu Jiahui , Wang Yanan , Ye Ying , Zhu Hui , Li Faqiang , Yu Haixiang , Cao Yangrong 
Published: December 2024

Summary
Plant immunity is suppressed in the symbiotic nodule cells, thereby facilitating rhizobial infection. Medicago truncatula NODULES WITH ACTIVATED DEFENSE1 (MtNAD1) is crucial for suppressing immunity in nodules; however, its molecular function is unclear.
We explored the molecular basis of the role of MtNAD1 in suppressing innate immunity in M. truncatula nodules.
Medicago truncatula mutants lacking MtATG7 produced defective nodules, sharing some similarities with the Mtnad1 mutant nodules. Furthermore, MtNAD1 interacted with several immunity‐related proteins, including BAX‐inhibitor1a (MtBI‐1a), two Lysin‐motif proteins (MtLYM1/2), Pathogenesis‐related10 (MtPR10c/d), MtMPK3/6, and two Lysin‐motif receptor kinases (MtLYK8/9). In addition, MtNAD1 and the autophagy pathway contributed to the reduction of MtBI‐1, MtPR10c/d, and MtLYM1/2 protein levels in planta. Knocking out either the MtBI‐1 or MtLYM1/2 gene in the M. truncatula nad1 mutant can partially restore the defective nodules of the nad1 mutant.
Our results demonstrate that MtNAD1 associates with the autophagy pathway by interacting with MtATG8, contributing to the degradation of several immunity‐related proteins in M. truncatula nodules during rhizobial colonization and thereby supporting the development of a successful symbiosis.
Stability of performance monitoring with prolonged task performance: A study of error‐related negativity and error positivity
Authors: Clayson Peter E. , Baldwin Scott A. , Larson Michael J. 
Published: December 2024

AbstractThe use of forced‐choice response tasks to study indices of performance monitoring, such as the error‐related negativity (ERN) and error positivity (Pe), is common, and such tasks are often used as a part of larger batteries in experimental research. ERN amplitude typically decreases over the course of a single task, but it is unclear whether amplitude changes persist beyond a single task or whether Pe amplitude changes over time. This preregistered study examined how prolonged task performance affects ERN and Pe amplitude across two study batteries, each with three different tasks. We predicted ERN amplitude would show unique, nonlinear reductions over an individual task and over the task battery, and exploratory analyses were conducted on Pe. Electrophysiological data were recorded during two studies: 156 participants who completed three versions of the flanker task and 161 participants who completed flanker, Go/NoGo, and Stroop tasks. ERN showed unique nonlinear reductions over each flanker task and over the battery of flanker tasks. However, ERN showed a linear reduction in amplitude over the battery of three different tasks, and within‐task changes were only observed during the Go/NoGo task, such that ERN increased. Pe generally linearly decreased with prolonged task performance. Variability in ERN and Pe scores generally increased with time, indicating decreases in data quality. Findings suggest that studying ERN and Pe early in a task battery with short tasks is optimal to avoid bias from prolonged performance. Identifying factors affecting ERN and Pe during prolonged performance can help develop optimized paradigms.
Polymorphisms in the type A
blaZ
gene as determinants of the cefazolin inoculum effect in
Staphylococcus aureus
Authors: Lee Shinwon , Park Sohee , Kim Jeong Nam , Lee Soon Ok , Lee Jeong Eun , Lee Sun Hee 
Published: December 2024

ABSTRACT

Plasmids containing the wild-type (WT) or mutant type A
blaZ
(
blaZ
A
) gene (mutations at codons 226, 229, or both 226 and 229) were constructed and transformed into
Staphylococcus aureus
RN4220, yielding the strains WT-blaZ, M226-blaZ, M229-blaZ, and MB-blaZ. The high-inoculum cefazolin MIC was significantly lower in MB-blaZ and M226-blaZ than in WT-blaZ but not in M229-blaZ, suggesting that the single nucleotide polymorphism at codon 226 in
blaZ
A
contributes to the cefazolin inoculum effect.
Ex vivo
assessment of sulbactam-durlobactam clearance during continuous renal replacement therapy to guide dosing recommendations
Authors: Abouelhassan Yasmeen , Shen Yuwei , Chen April , Ye Xiaoyi , Nicolau David P. , Kuti Joseph L. 
Published: December 2024

ABSTRACT

Sulbactam-durlobactam is approved for the treatment of hospital-acquired and ventilator-associated bacterial pneumonia caused by susceptible isolates of
Acinetobacter baumannii-calcoaceticus
complex. Patients with serious
Acinetobacter
infections may require support with continuous renal replacement therapy (CRRT), which presents challenges for optimal dosing of antibiotics. Sulbactam-durlobactam dosing regimens were derived for this population using an
ex vivo
CRRT model and Monte Carlo simulation (MCS). Transmembrane clearance (CL
TM
) was determined in hemofiltration (CVVH) and hemodialysis (CVVHD) modes using the Prismaflex M100 and HF1400 hemofilter sets and with effluent rates of 1, 2, and 3 L/h. Pre-filter, post-filter blood, and effluent samples were collected over 60 min to calculate sieving (SC) and saturation (SA) coefficients for CVVH and CVVHD, respectively. An established population pharmacokinetic model was integrated with the CL
TM
; then, a 1,000 patient MCS was conducted to determine exposures of potential dosing regimens. Adsorption and degradation in the
ex vivo
CRRT model were negligible. The overall mean ± standard deviation SC/SA was 1.14 ± 0.12 and 0.93 ± 0.08 for sulbactam and durlobactam, respectively. In multivariable regression analyses, effluent rate was the primary driver of CL
TM
for both drugs. For effluent rates <3 L/h, sulbactam-durlobactam 1 g-1g q8h as 3 h infusion achieved a high probability of pharmacodynamic target attainment while retaining area under the curve exposures consistent with the standard dose in non-CRRT patients. For effluent rates ≥3 to 5 L/h, the optimal regimen was 1 g-1g q6h 3 h infusion. Sulbactam-durlobactam regimens that provide optimum drug exposures for efficacy and safety were identified for CRRT based on the prescribed effluent rate.
Third intracellular loop of HCMV US28 is necessary for signaling and viral reactivation
Authors: Medica Samuel , Denton Michael , Diggins Nicole L. , Kramer-Hansen Olivia , Crawford Lindsey B. , Mayo Adam T. , Perez Wilma D. , Daily Michael A. , Parkins Christopher J. , Slind Luke E. , Pung Lydia J. , Weber Whitney C. , Jaeger Hannah K. , Streblow Zachary J. , Sulgey Gauthami , Kreklywich Craig N. , Alexander Timothy , Rosenkilde Mette M. , Caposio Patrizia , Hancock Meaghan H. , Streblow Daniel N. 
Published: December 2024

ABSTRACT

The human cytomegalovirus (HCMV) encoded chemokine receptor US28 plays a critical role in viral pathogenesis, mediating several processes such as cellular migration, differentiation, transformation, and viral latency and reactivation. Despite significant research examining the signal transduction pathways utilized by US28, the precise mechanism by which US28 activates these pathways remains unclear. We performed a mutational analysis of US28 to identify signaling domains that are critical for functional activities. Our results indicate that specific residues within the third intracellular loop (ICL3) of US28 are major determinants of G-protein coupling and downstream signaling activity. Alanine substitutions at positions S218, K223, and R225 attenuated US28-mediated activation of MAPK and RhoA signal transduction pathways. Furthermore, we show that mutations at positions S218, K223, or R225 result in impaired coupling to multiple Gα isoforms. However, these substitutions did not affect US28 plasma membrane localization or the receptor internalization rate. Utilizing CD34
+
HPC models, we demonstrate that attenuation of US28 signaling
via
mutation of residues within the ICL3 region results in an inability of the virus to efficiently reactivate from latency. These results were recapitulated
in vivo
, utilizing a humanized mouse model of HCMV infection. Together, our results provide new insights into the mechanism by which US28 manipulates host signaling networks to mediate viral latency and reactivation. The results reported here will guide the development of targeted therapies to prevent HCMV-associated disease.

IMPORTANCE

Human cytomegalovirus (HCMV) is a β-herpesvirus that infects between 44% and 100% of the world population. Primary infection is typically asymptomatic and results in the establishment of latent infection within CD34
+
hematopoietic progenitor cells (HPCs). However, reactivation from latent infection remains a significant cause of morbidity and mortality in immunocompromised individuals. The viral chemokine receptor US28 influences various cellular processes crucial for viral latency and reactivation, yet the precise mechanism by which US28 functions remains unclear. Through mutational analysis, we identified key residues within the third intracellular loop (ICL3) of US28 that govern G-protein coupling, downstream signaling, and viral reactivation
in vitro
and
in vivo
. These findings offer novel insights into how US28 manipulates host signaling networks to regulate HCMV latency and reactivation and expand our understanding of HCMV pathogenesis.
Rapid diagnosis of bacterial vaginosis using machine-learning-assisted surface-enhanced Raman spectroscopy of human vaginal fluids
Authors: Wen Xin-Ru , Tang Jia-Wei , Chen Jie , Chen Hui-Min , Usman Muhammad , Yuan Quan , Tang Yu-Rong , Zhang Yu-Dong , Chen Hui-Jin , Wang Liang 
Published: December 2024

ABSTRACT

Bacterial vaginosis (BV) is an abnormal gynecological condition caused by the overgrowth of specific bacteria in the vagina. This study aims to develop a novel method for BV detection by integrating surface-enhanced Raman scattering (SERS) with machine learning (ML) algorithms. Vaginal fluid samples were classified as BV positive or BV negative using the BVBlue Test and clinical microscopy, followed by SERS spectral acquisition to construct the data set. Preliminary SERS spectral analysis revealed notable disparities in characteristic peak features. Multiple ML models were constructed and optimized, with the convolutional neural network (CNN) model achieving the highest prediction accuracy at 99%. Gradient-weighted class activation mapping (Grad-CAM) was used to highlight important regions in the images for prediction. Moreover, the CNN model was blindly tested on SERS spectra of vaginal fluid samples collected from 40 participants with unknown BV infection status, achieving a prediction accuracy of 90.75% compared with the results of the BVBlue Test combined with clinical microscopy. This novel technique is simple, cheap, and rapid in accurately diagnosing bacterial vaginosis, potentially complementing current diagnostic methods in clinical laboratories.

IMPORTANCE
The accurate and rapid diagnosis of bacterial vaginosis (BV) is crucial due to its high prevalence and association with serious health complications, including increased risk of sexually transmitted infections and adverse pregnancy outcomes. Although widely used, traditional diagnostic methods have significant limitations in subjectivity, complexity, and cost. The development of a novel diagnostic approach that integrates SERS with ML offers a promising solution. The CNN model’s high prediction accuracy, cost-effectiveness, and extraordinary rapidity underscore its significant potential to enhance the diagnosis of BV in clinical settings. This method not only addresses the limitations of current diagnostic tools but also provides a more accessible and reliable option for healthcare providers, ultimately enhancing patient care and health outcomes.