bluuebunny/crossref_metadata_2025_split huggingface dataset:
The three-dimensional structure of the EBV genome plays a crucial role in regulating viral gene expression in EBVaGC
Authors: Maestri Davide , Napoletani Giorgia , Kossenkov Andrew , Preston-Alp Sarah , Caruso Lisa B , Tempera Italo 
Published: October 2023

Abstract
Epstein–Barr virus (EBV) establishes lifelong asymptomatic infection by replication of its chromatinized episomes with the host genome. EBV exhibits different latency-associated transcriptional repertoires, each with distinct three-dimensional structures. CTCF, Cohesin and PARP1 are involved in maintaining viral latency and establishing episome architecture. Epstein–Barr virus-associated gastric cancer (EBVaGC) represents 1.3–30.9% of all gastric cancers globally. EBV-positive gastric cancers exhibit an intermediate viral transcription profile known as ‘Latency II’, expressing specific viral genes and noncoding RNAs. In this study, we investigated the impact of PARP1 inhibition on CTCF/Cohesin binding in Type II latency. We observed destabilization of the binding of both factors, leading to a disrupted three-dimensional architecture of the episomes and an altered viral gene expression. Despite sharing the same CTCF binding profile, Type I, II and III latencies exhibit different 3D structures that correlate with variations in viral gene expression. Additionally, our analysis of H3K27ac-enriched interactions revealed differences between Type II latency episomes and a link to cellular transformation through docking of the EBV genome at specific sites of the Human genome, thus promoting oncogene expression. Overall, this work provides insights into the role of PARP1 in maintaining active latency and novel mechanisms of EBV-induced cellular transformation.
Paralysed Governments: How Political Constraints Elicit Cabinet Termination
Authors: Improta Marco 
Published: October 2023

Abstract
A crucial feature of the democratic life cycle, government stability, has prompted the interest of many scholars across the globe. As a result, research on this matter has established itself as one of the most developed agendas in comparative politics. However, despite the abundance of studies on the drivers of government stability, the ruling parties’ capacity to promote policy change when in government remains unexplored. This study aims to fill this lacuna by testing the effect of political constraints on the premature end of cabinets. It does so by leveraging an original longitudinal multilevel dataset comprising information on 429 governments in 20 Western European countries on which event history analyses are performed. The study’s findings show that high political constraints significantly increase the risk of cabinet termination, indicating that seeking to survive in office without governing can be an impassable road for ruling parties.
Association between serum interleukin-17 levels and ectopic bone formation in OPLL patients with DISH
Authors: He Zhongyuan , Tung Nguyen Tran Canh , Yahara Yasuhito , Makino Hiroto , Yasuda Taketoshi , Seki Shoji , Suzuki Kayo , Futakawa Hayato , Kamei Katsuhiko , Kawaguchi Yoshiharu 
Published: October 2023

Abstract

Objective
To investigate the relationship between the severity and morphology of heterotopic ossification in the spinal ligaments including sacroiliac (SI) joints, and serum interleukin-17 (IL-17) levels in patients with ossification of the posterior longitudinal ligament (OPLL) with or without diffuse idiopathic skeletal hyperostosis (DISH), as well as a non-OPLL group.

Methods
A total of 103 patients with OPLL [DISH (−), n = 50; DISH (+), n = 53] and 53 age- and gender-matched controls were included. The serum levels of IL-17 were analysed, and the severity of ectopic ossification and the morphology of ectopic bone formation were evaluated. The SI joint morphological variations were categorized into four types.

Results
No significant differences were found in serum IL-17 levels between the OPLL and control groups. However, the DISH (+) group showed higher IL-17 levels than the DISH (−) group, especially in female patients (P = 0.003). Additionally, IL-17 levels were positively correlated with the number of flat vertebral units, this being one of the characteristic DISH ossification types (R2 = 0.199, P = 0.012). IL-17 levels in the type showing bridging osteophyte and bone fusion were significantly higher in the DISH (+) group than in the DISH (−) group.

Conclusion
The morphological characteristics of paravertebral bone formation in the entire spine, including the SI joint, are likely associated with serum IL-17 levels in OPLL. These findings provide pathological and serological evidence of local inflammation contributing to paravertebral ossification of OPLL patients.
Public perception of scientific advisory bodies: the case of France’s Covid-19 Scientific Council
Authors: Schultz Émilien , Ward Jeremy K , Atlani-Duault Laëtitia 
Published: October 2023

AbstractDuring the Covid-19 pandemic, many governments have resorted to scientific advisory bodies to aid in public health decision-making. What then has been the public’s perception of those new structures of scientific advice? In this article, we draw on a survey conducted in November 2020 among a representative sample of the French adult population (n = 1,004) designed specifically to explore public perceptions of the dedicated Covid-19 Scientific Council created in March 2020 and of scientific advice in general. After only 8 months, three-quarters of French people said they had heard of it, but only a quarter had a positive opinion about its usefulness. Despite the diversity of perceptions of what scientific advice is and should be, it appeared that scientific advice bodies are perceived as useful mainly by a public already largely supportive of the delegation of the management of public life to the government and public institutions.
Foxk1 stimulates adipogenic differentiation via a peroxisome proliferator‐activated receptor gamma 2‐dependent mechanism
Authors: Zhang Shan , You Yanru , Li Yachong , Yuan Hairui , Zhou Jie , Tian Lijie , Liu Ying , Wang Baoli , Zhu Endong 
Published: October 2023

AbstractAdipogenesis is a tightly regulated process, and its dysfunction has been linked to metabolic disorders such as obesity. Forkhead box k1 (Foxk1) is known to play a role in the differentiation of myogenic precursor cells and tumorigenesis of different types of cancers; however, it is not clear whether and how it influences adipocyte differentiation. Here, we found that Foxk1 was induced in mouse primary bone marrow stromal cells (BMSCs) and established mesenchymal progenitor/stromal cell lines C3H/10T1/2 and ST2 after adipogenic treatment. In addition, obese db/db mice have higher Foxk1 expression in inguinal white adipose tissue than nonobese db/m mice. Foxk1 overexpression promoted adipogenic differentiation of C3H/10T1/2, ST2 cells and BMSCs, along with the enhanced expression of CCAAT/enhancer binding protein‐α, peroxisome proliferator‐activated receptor γ (Pparγ), and fatty acid binding protein 4. Moreover, Foxk1 overexpression enhanced the expression levels of lipogenic factors during adipogenic differentiation in both C3H/10T1/2 cells and BMSCs. Conversely, Foxk1 silencing impaired these cells from fully differentiating. Furthermore, adipogenic stimulation induced the nuclear translocation of Foxk1, which depended on the mTOR and PI3‐kinase signaling pathways. Subsequently, Foxk1 is directly bound to the Pparγ2 promoter, stimulating its transcriptional activity and promoting adipocyte differentiation. Collectively, our study provides the first evidence that Foxk1 promotes adipocyte differentiation from progenitor cells by promoting nuclear translocation and upregulating the transcriptional activity of the Pparγ2 promoter during adipogenic differentiation.
Severe Acute Respiratory Syndrome Coronavirus 2 Pneumonia in Critically Ill Patients: A Cluster Analysis According to Baseline Characteristics, Biological Features, and Chest CT Scan on Admission
Authors: Grapin Kévin , De Bauchene Romain , Bonnet Benjamin , Mirand Audrey , Cassagnes Lucie , Calvet Laure , Thouy François , Bouzgarrou Radhia , Henquell Cécile , Evrard Bertrand , Adda Mireille , Souweine Bertrand , Dupuis Claire 
Published: October 2023

BACKGROUND:
Inconsistent results from COVID-19 studies raise the issue of patient heterogeneity.

OBJECTIVE:
The objective of this study was to identify homogeneous subgroups of patients (clusters) using baseline characteristics including inflammatory biomarkers and the extent of lung parenchymal lesions on CT, and to compare their outcomes.

DESIGN:
Retrospective single-center study.

SETTING:
Medical ICU of the University Hospital of Clermont-Ferrand, France.

PATIENTS:
All consecutive adult patients aged greater than or equal to 18 years, admitted between March 20, 2020, and August 31, 2021, for COVID-19 pneumonia.

INTERVENTIONS:
Characteristics at baseline, during ICU stay, and outcomes at day 60 were recorded. On the chest CT performed at admission the extent of lung parenchyma lesions was established by artificial intelligence software.

MEASUREMENTS AND MAIN RESULTS:
Clusters were determined by hierarchical clustering on principal components using principal component analysis of admission characteristics including plasma interleukin-6, human histocompatibility leukocyte antigen-DR expression rate on blood monocytes (HLA-DR) monocytic-expression rate (mHLA-DR), and the extent of lung parenchymal lesions. Factors associated with day 60 mortality were investigated by univariate survival analysis. Two hundred seventy patients were included. Four clusters were identified and three were fully described. Cluster 1 (obese patients, with moderate hypoxemia, moderate extent of lung parenchymal lesions, no inflammation, and no down-regulation of mHLA-DR) had a better prognosis at day 60 (hazard ratio [HR] = 0.27 [0.15–0.46], p < 0.01), whereas cluster 2 (older patients with comorbidities, moderate extent of lung parenchyma lesions but significant hypoxemia, inflammation, and down-regulation of mHLA-DR) and cluster 3 (patients with severe parenchymal disease, hypoxemia, inflammatory reaction, and down-regulation of mHLA-DR) had an increased risk of mortality (HR = 2.07 [1.37–3.13], p < 0.01 and HR = 1.52 [1–2.32], p = 0.05, respectively). In multivariate analysis, only clusters 1 and 2 were independently associated with day 60 death.

CONCLUSIONS:
Three clusters with distinct characteristics and outcomes were identified. Such clusters could facilitate the identification of targeted populations for the next trials.
The evolution of pharmacovigilance: the contributions of Michael D Rawlins
Authors: Routledge Philip A. 
Published: October 2023

Summary
In the last 175 years, pharmacovigilance has evolved, albeit sometimes in response to serious incidents. The late Professor Sir Michael D Rawlins made major contributions to pharmacovigilance internationally. He proposed a widely used classification of adverse drug reactions (ADRs). He highlighted the importance of post-marketing surveillance immediately after a medicine's launch, and the strengths and weaknesses of existing spontaneous suspected ADR reporting systems. He encouraged the broadening of pharmacovigilance to involve all health professional groups, as well as patients. He highlighted the value of all sources of evidence and of judgement in making risk-benefit assessments. He was a strong early advocate of greater use of databases and registries, and of continuing surveillance throughout the lifespan of medicines as therapeutic agents.
Reliability of systolic blood pressure measured by parents in young children at home using a hand held doppler device and aneroid sphygmomanometer
Authors: Newton Joanna , Haseler Emily , Higgins Colin , Futcher Charlotte , Singh Cheentan , Sinha Manish D. 
Published: October 2023

Objective:
We report data regarding systolic BP monitoring in children aged <5 years performed over a 2-week period by parents at home using a hand-held doppler device and aneroid sphygmomanometer for SBP measurements (HDBPM). Our objectives were to compare health professional measured office systolic BP by doppler device (Office-SBPDoppler) with parent measured home systolic BP using the same doppler device (Home-SBPDoppler). We also report data evaluating reliability and optimal number of days of measurement required.

Design and Methods:
We taught parents to measure systolic BP and assessed their technique using a hand-held doppler device and aneroid sphygmomanometer. We requested parents to perform three consecutive BP measurements twice daily (ideally morning and evening around similar times) when the child was awake, settled and cooperative.

Results:
Over a 3-year period, data from 48 of 62 children who underwent HDBPM measurements were evaluated with median (IQR) age of 1.9 (0.9, 3.6) years, 27 (56%) boys and 14 (29%) on antihypertensive medication. Office-SBPDoppler was 2.9 ± 8.9 mmHg [95% confidence interval (CI), −14.4 to 20.4, P = 0.026] higher than Home-SBPDoppler. Mean Home-SBPDoppler between Week-1 and Week-2 monitoring was similar −0.45 ± 3.5 mmHg (95% CI, −7.35 to 6.45, P = 0.41). Morning HDBPM measurements were lower than evening with a mean difference of -2.77 ± 3.92 mmHg, P < 0.001). Over Week-1, mean Home-SBPDoppler was closer to mean Office-SBPDoppler with increasing cumulative days of monitoring and with smaller standard deviations suggesting that readings become more reliable from day 4 onwards.

Conclusions:
HDBPM is a reliable method for measuring systolic BP in young children with BP levels measured by parents comparable to those performed by health professional in clinic. HDBPM technique described here and performed by parents over a 7-day period with a minimum of 4-days, offers a reliable and reproducible technique to measure blood pressure at home.
Inflammation, lipid dysregulation, and transient receptor potential cation channel subfamily V member 4 signaling perpetuate chronic vulvar pain
Authors: Bekauri Tamari , Fischer Sarah , Honn Kenneth V. , Maddipati Krishna Rao , Love Tanzy , Little Chantelle , Wood Ronald W. , Bonham Adrienne D. , Linder Mitchell A. , Yule David I. , Emanuelle Chrysilla , Falsetta Megan L. 
Published: October 2023

Abstract
Localized provoked vulvodynia is characterized by chronic vulvar pain that disrupts every aspect of the patient's life. Pain is localized to the vulvar vestibule, a specialized ring of tissue immediately surrounding the vaginal opening involved in immune defense. In this article, we show inflammation is the critical first step necessary for the generation of pain signals in the vulva. Inflammatory stimuli alone or combined with the transient receptor potential cation channel subfamily V member 4 (TRPV4) agonist 4α-phorbol 12,13-didecanoate stimulate calcium flux into vulvar fibroblast cells. Activity is blocked by the TRPV4 antagonist HC067047, denoting specificity to TRPV4. Using lipidomics, we found pro-resolving lipids in the vulvar vestibule were dysregulated, characterized by a reduction in pro-resolving mediators and heightened production of inflammatory mediators. We demonstrate specialized pro-resolving mediators represent a potential new therapy for vulvar pain, acting on 2 key parts of the disease mechanism by limiting inflammation and acutely inhibiting TRPV4 signaling.
Race differences in ambulatory blood pressure monitoring parameters
Authors: Sakhuja Swati , Jaeger Byron C. , Yano Yuichiro , Shimbo Daichi , Lewis Cora E. , Clark III Donald , Tajeu Gabriel S. , Hardy Shakia T. , Allen Norrina B. , Shikany James M. , Schwartz Joseph E. , Viera Anthony J. , Muntner Paul 
Published: October 2023

Background
Mean systolic and diastolic blood pressure (SBP and DBP) on ambulatory blood pressure (BP) monitoring (ABPM) are higher among Black compared with White adults. With 48 to 72 BP measurements obtained over 24 h, ABPM can generate parameters other than mean BP that are associated with increased risk for cardiovascular events. There are few data on race differences in ABPM parameters other than mean BP.

Methods
To estimate differences between White and Black participants in ABPM parameters, we used pooled data from five US-based studies in which participants completed ABPM (n = 2580). We calculated measures of SBP and DBP level, including mean, load, peak, and measures of SBP and DBP variability, including average real variability (ARV) and peak increase.

Results
There were 1513 (58.6%) Black and 1067 (41.4%) White participants with mean ages of 56.1 and 49.0 years, respectively. After multivariable adjustment, asleep SBP and DBP load were 5.7% (95% CI: 3.5–7.9%) and 2.7% (95% CI: 1.1–4.3%) higher, respectively, among Black compared with White participants. Black compared with White participants also had higher awake DBP ARV (0.3 [95%CI: 0.0–0.6] mmHg) and peak increase in DBP (0.4 [95% CI: 0.0–0.8] mmHg). There was no evidence of Black:White differences in awake measures of SBP level, asleep peak SBP or DBP, awake and asleep measures of SBP variability or asleep measures of DBP variability after multivariable adjustment.

Conclusion
Asleep SBP load, awake DBP ARV and peak increase in awake DBP were higher in Black compared to White participants, independent of mean BP on ABPM.
Kidney disease hotspots and water balance in a warming world
Authors: Contreras Nieves Marimar , Powers Angelina , Anand Shuchi , Vlahos Penny 
Published: October 2023

Purpose of review
Geographically localized areas with a high prevalence of kidney disease exist currently in several regions of the world. Although the exact cause is unclear, environmental exposures accelerated by climate change, particularly heat exposure and ground water contamination, are hypothesized as putative risk factors. Aiming to inform investigations of water-related exposures as risk factors for kidney disease, we excavate the history of major water sources in three regions that are described as hotspots of kidney disease: the low-lying coastal regions in El Salvador and Nicaragua, the dry central region in Sri Lanka, and the Central Valley of California.

Recent findings
Historic data indicate that these regions have experienced water scarcity to which several human-engineered solutions were applied; these solutions could be hypothesized to increase residents’ exposure to putative kidney toxins including arsenic, fluoride, pesticides, and cyanobacteria. Combined with heat stress experienced in context of climate change, there is potential for multistressor effects on kidney function. Climate change will also amplify water scarcity, and even if regional water sources are not a direct risk factor for development of kidney disease, their scarcity will complicate the treatment of the relatively larger numbers of persons with kidney disease living in these hotspots.

Summary
Nephrologists and kidney disease researchers need to engage in systematic considerations of environmental exposures as potential risk factors for kidney disease, including water sources, their increasing scarcity, and threats to their quality due to changing climate.
Early Prelicensure Nursing Students' Perceptions of Case Studies Through the Lens of the Clinical Judgment Measurement Model
Authors: Robinson Laurie , Mulvey Bridget K. , Aller Loretta 
Published: October 2023

Background:
Research indicates new nursing graduates struggle with clinical reasoning, despite some related skill development throughout their education. The question remains, “Could an earlier focus on clinical reasoning in nursing programs enhance nursing students' clinical reasoning?”

Purpose:
This pilot study investigated how first-semester nursing students perceive the use of case studies in clinical reasoning skill development and the perceived benefits of case studies related to the NCSBN Clinical Judgment Measurement Model (NCJMM).

Methods:
Case studies and written reflections were introduced to a convenience sample (n = 45) of first-semester nursing students. Qualitative analysis was conducted on written reflections.

Results:
Students found case studies enhanced their knowledge and prepared them for clinical practice as a nurse.

Conclusions:
Findings suggest early introduction of case studies is a meaningful teaching strategy to develop clinical reasoning aligned with the NCJMM.
Impact of Nursing Clinical Elective Courses on New Graduate Nurses' Clinical Practice
Authors: Lewis Lisa S. , Hartman A. Michelle , Leonard Christina , Cadavero Allen , Reynolds Staci S. 
Published: October 2023

Background:
Clinical elective courses provide additional specialty knowledge for prelicensure nursing students; however, it is unknown how these courses impact nurses' clinical practice after graduation.

Purpose:
To describe how clinical nursing electives impact graduates' clinical practice.

Methods:
A mixed-methods descriptive design was used. Students who graduated from a prelicensure nursing program were sent an electronic survey and participated in qualitative interviews.

Results:
Thirty-three graduates completed the survey, with 9 participating in interviews. Sixteen graduates worked in the clinical practice areas that were the same, or related to, the clinical elective they took. Many graduates felt that taking the elective course improved their confidence in the clinical setting and provided increased knowledge that put them at an advantage over their peers.

Conclusion:
Clinical electives may offer a means to meet health care system needs by preparing a more confident, knowledgeable new graduate in specialty areas in which nurses are needed most.
The Tenacious Treponema: A Retrospective Examination of Syphilis Treatment Disparities in Washington, DC
Authors: Liroff Kaitlin , Kassaye Seble G. , Spence Amanda B. , Kumar Princy N. , Natarajan Madhuri , Harold Rachel , Dorsey Kerri , Doshi Rupali K. , Visconti Adam J. 
Published: October 2023

AbstractBackgroundSince 2000 there have been rising rates of syphilis infections nationally with higher incidence among minorities and persons living with HIV (PLWH). The purpose of this study was to determine syphilis treatment adequacy and factors associated with treatment delay.MethodsThis was a retrospective academic-public health collaboration with the District of Columbia Department of Public Health reviewing surveillance data of all primary, secondary, and early latent syphilis cases diagnosed between 1/1/2015 and 12/31/2019. Data were analyzed using multivariable logistic regression to identify factors associated with delayed treatment >14 days from diagnosis.ResultsAmong 1852 individuals diagnosed with early syphilis, 93% (1730/1852) were male; 48% (893/1852) were co-infected with HIV; 43% (n = 796/1852) were African American/Black, 27% (n = 492/1852) were White, and race/ethnicity was unknown for 17% (n = 318/1852) of cases. Among 679 PLWH for whom viral load (VL) was known, 41% (278/679) had a viral load (VL) < 20 copies/mL, and 18% (123/679) had VL >10,000 copies/mL. Treatment adequacy overall was 96.5%. Median time to syphilis treatment was 6 days [IQR = 4,7]. Factors associated with delay of treatment included refused/unknown race (aOR = 1.95; CI = 1.00, 3.79), reporting provider veterans/military (aOR = 5.26; (CI = 1.51-18.28),and HIV VL > 10,000 copies/mL (aOR = 1.97; CI = 1.08-3.58).ConclusionsThe factors we identified associated with delayed treatment may reflect systemic factors contributing to the increased rates of infection among key populations. This highlights the importance of targeted public health efforts with the goal of reducing transmission of both HIV and syphilis.