bluuebunny/crossref_metadata_2025_split huggingface dataset:
The rapid activation of cPKCβII by progesterone results in the negative regulation of Ca2+ influx in human resting T cells
Authors: Lin Veronica Hui-Chen , Chien Angela , Chien Eileen Jea 
Published: July 2023

Background:
Progesterone-stimulated rapid suppression of phytohemagglutinin (PHA)-activated sustained membrane Ca2+ influx is revealed by Mn2+ quenching fura-2 fluorescence. Ca2+ influx suppression results in immunosuppression of T-cell proliferation. Downregulation of protein kinase C (PKC) activity by phorbol 12-myristate 13-acetate (PMA) enhances the PHA-activated increase in sustained intracellular Ca2+ concentration ([Ca2+]i) via Ca2+ influx in T cells. Conventional PKC (cPKC) inhibitors also enhance the [Ca2+]i increase in resting T cells caused by progesterone. This study explores whether cPKC activation by progesterone results in suppression of Ca2+ influx in resting T cells.

Methods:
Progesterone, its analogs (R5020/Org OD 02-0), and plasma membrane-impermeable progesterone-bovine serum albumin conjugate were used to stimulate human resting T cells. Inhibitors and PKC downregulation by PMA were used to investigate whether cPKC affects Ca2+ influx.

Results:
Progesterone and analogs dose-dependently suppressed Ca2+ influx in T cells. One cPKC inhibitor, Ro318220, attenuated Ca2+ influx suppression, and enhanced the increase in [Ca2+]i caused by progesterone and analogs. U73122 did not affect Ca2+ influx suppression but did decrease the [Ca2+]i increase. Ca2+ influx suppression was not attenuated by the cPKCα/βI isoform-selective inhibitor, Go6976, nevertheless, a cPKCβI/βII isoform-selective inhibitor, LY333531 did. Ca2+ influx suppression was attenuated by the cPKCβII-specific inhibitor CGP53353. After PKC downregulated by PMA, Ca2+ influx suppression by progesterone and analogs was almost abolished in parallel with a massive reduction in cPKCβII expression. This suggests cPKCβII activation by progesterone and analogs mediate Ca2+ influx suppression in resting T cells.

Conclusion:
Nongenomic membrane activation of cPKCβII by progesterone causes immunosuppression via negative regulation of Ca2+ influx into human resting T cells. This prevents resting T-cell activation and proliferation, which protects the fetus from maternal immune attack while decreasing maternal autoimmune disease flare-ups during pregnancy. Thus, cPKCβII modulators might provide a new therapeutic approach to balancing T-cell tolerance and immunity.
Dynamic evaluation based on acute-on-chronic liver failure predicts survival of patients after liver transplantation: a cohort study
Authors: Zhang Wei , Jin Pingbo , Liu Junfang , Wu Yue , Wang Rongrong , Zhang Yuntao , Shen Yan , Zhang Min , Bai Xueli , Fung John , Liang Tingbo 
Published: July 2023

Background & Aims:
Dynamic evaluation of critically ill patients is the key to predicting their outcomes. Most scores based on Model for End-stage Liver Disease (MELD) and acute-on-chronic liver failure (ACLF) utilize point-in-time assessment. This study mainly aimed to investigate the impact of dynamic clinical course change on post-liver transplantation survival.

Methods
This study included 637 adults (overall cohort) with benign end-stage liver diseases. We compared the MELD scores and our ACLF-based dynamic evaluation scores. Patients enrolled or transplanted with ACLF3 were defined as ACLF-3 cohort (n = 158). The primary outcome was 1-year mortality. ΔMELD and ΔCLIF-OF represented the respective dynamic changes in liver transplant function. Discrimination was assessed using the area under the curve (AUC). Cox regression analysis identified independent risk factors for specific organ failure and 1-year mortality.

Results:
Patients were grouped as deterioration group, stable group, and improvement group. The deterioration group (ΔCLIF-OF ≥ 2) was more likely to receive national liver allocation (P=0.012) but experienced longer cold ischemia time (P=0.006) than other groups. The AUCs for ΔCLIF-OF were 0.752 for the entire cohort and 0.767 for ACLF-3 cohorts, both superior to ΔMELD (P<0.001 for both). Compared to the improvement group, the 1-year mortality hazard ratios (HR) of deterioration group were 12.57 (6.72–23.48) for overall cohort and 7.00 (3.73–13.09) for ACLF-3 cohort. Extrahepatic organs subscore change (HR=1.783 (1.266-2.512) for neurologic; 1.653 (1.205-2.269) for circulation; 1.906 (1.324-2.743) for respiration; 1.473 (1.097-1.976) for renal) were key to transplantation outcomes in the ACLF-3 cohort. CLIF-OF at LT (HR=1.193), ΔCLIF-OF (HR=1.354), and cold ischemia time (HR=1.077) were independent risk factors of mortality for the overall cohort, while ΔCLIF-OF (HR=1.384) was the only independent risk factor for the ACLF-3 cohort. Non-ACLF3 patients showed a higher survival rate than patients with ACLF-3 in all groups (P=0.002 for I, P=0.005 for S and P=0.001 for D).

Conclusion:
This was the first ACLF-based dynamic evaluation study. ΔCLIF-OF was a more powerful predictor of post-LT mortality than ΔMELD. Extrahepatic organ failures were core risk factors for ACLF-3 patients. CLIF-OF at LT, ΔCLIF-OF, and cold ischemia time were independent risk factors for post-LT mortality. Patients with a worse baseline condition and deteriorating clinical course had the worst prognosis. Dynamic evaluation was important in risk stratification and recipient selection.
Bicuspid aortic valve and its ascending aortopathy
Authors: Dunne Emma C. , Lacro Ronald V. , Flyer Jonathan N. 
Published: July 2023

Purpose of review
To synthesize and critically assess recent clinical and research advancements in pediatric bicuspid aortic valve (BAV) and its associated aortopathy.

Recent findings
In pediatric patients with BAV, progressive aortic dilation (i.e. bicuspid aortopathy) is commonly present and associated with increased risk for aortic aneurysm, dissection, and surgery in adulthood. Ongoing research explores the cause, incidence, and progression of bicuspid aortopathy to promote earlier diagnosis and improve preventive management. Recent findings include: high familial incidence and need for improved familial screening; safety of recreational physical activity in most affected children; potential for medical management to slow aortic growth; feasibility of pediatric registries to evaluate longitudinal outcomes; and potential genetic and hemodynamic biomarkers for disease risk stratification.

Summary
Pediatric bicuspid aortopathy is an important area for investigation and preventive management to improve long-term cardiovascular outcomes. Recent literature promotes familial screening, recreational exercise, medical prophylaxis, registry-based longitudinal evaluation, and continued scientific inquiry.
Population-Level Disparities in Exposure to COVID-19 Mitigation Policies, April 2020-April 2021
Authors: Douglas Megan D. , Li Chaohua , Josiah Willock Robina , Baltrus Peter , Caplan Lee , Immergluck Lilly , McKinney Tonyka , Hopkins Jammie , Mack Dominic , Gaglioti Anne H. 
Published: July 2023

Context:
Studies have found that COVID-19 stay-at-home orders (SHOs) and face mask policies (FMPs) were associated with reduced COVID-19 transmission and deaths. But it is unknown whether exposure to these policies varied by sociodemographic characteristics across the US population.

Objective:
The goal of this study was to quantify and characterize the sociodemographic characteristics and geographic distribution of populations exposed to evidence-based COVID-19 mitigation policies.

Design:
We obtained statewide SHOs and FMPs for all US counties from April 10, 2020, to April 10, 2021, calculated median policy lengths, and categorized counties into 4 groups based on length of policy exposure: low SHO-low FMP, high SHO-low FMP, low SHO-high FMP, and high SHO-high FMP. We described exposure groups by COVID-19 cumulative case/death and vaccination rates and county sociodemographic characteristics.

Setting:
In total, 3142 counties from all 50 states and Washington, District of Columbia, were included in the analysis.

Main Outcome Measures:
County-level sociodemographic factors and county cumulative rates for COVID-19 cases, deaths, and vaccinations.

Results:
The largest percentage of the US population lived in counties with high exposure to SHOs and FMPs. However, populations living in high SHO-high FMP counties had the lowest percent non-Hispanic Black (NHB) and highest percent non-Hispanic White (NHW) populations. Populations living in high SHO-low FMP counties had the highest percent NHB and Hispanic populations and the lowest percent NHW population.

Conclusion:
This study identified county-level racial, ethnic, and sociodemographic disparities in exposure to evidence-based statewide COVID-19 mitigation policies.

Policy Implications:
Exposure to evidence-based policies is an important consideration for studies evaluating the root causes of health inequities.
Community-Dwelling Adults' Perceived Versus Actual Risk of Cardiovascular Disease, Body Mass Index, and Physical Activity Levels and Related Factors
Authors: Gözüm Sebahat , Dağıstan Akgöz Ayşe 
Published: July 2023

Context:
The difference between actual and perceived risk levels shows distorted risk perception. Unrealistic perceptions of cardiovascular disease (CVD) risks and insufficient knowledge about CVD risk factors can not only hinder the adoption of a positive lifestyle change but also obstruct preventive efforts.

Objective:
The aim of this study was to evaluate the concordance between perceived and actual risks, body mass index (BMI), and physical activity levels.

Design:
This descriptive study included 522 community-dwelling adults in 2 different regions of Antalya/Turkey. The actual CVD risk level of the participants was determined using the “HeartScore program,” actual body weight was determined according to BMI, and actual activity levels were found using the “International Physical Activity Questionnaire Short Form (IPAQ-SF).” The perceived risks were measured with the CVD Risk and Risk Factors Perception Determination Questionnaire. CVD Risk Factors Knowledge Level (CARRF-KL) Scale was used to calculate the participants' level of knowledge about the risk factors.

Results:
There was no concordance between the participants' actual and perceived CVD risks. A below-average agreement was found between the participants' actual and perceived BMI levels. In terms of actual measurements, it was seen that slightly obese individuals have a realistic perception. There was a weak agreement between the actual and perceived physical activity levels of the adults. Knowledge about the CVD risk factors of adults does not affect the perception of CVD risk and BMI and physical activity.

Conclusions:
Adults have an optimistic risk perception regarding CVD risk, BMI, and physical activity levels. It may be beneficial to periodically assess actual risks to change skewed perceptions of CVD and risk factors. These findings will inform the development of tailored intervention strategies and policies for these adults.
A Strategy for Strengthening: Implementation of the Capabilities Opportunities Assessment Tool for the Public Health Workforce
Authors: Hughes Monica J. , Kuehnert Paul , Swider Susan M. 
Published: July 2023

Context:
Strengthening the national public health infrastructure is crucial to ensure provision of necessary public health services in all jurisdictions. Public health agencies and their governing bodies need an evidence-based understanding of workforces' capabilities to operationalize this effort.

Program:
The Capabilities Opportunities Assessment Tool for the Public Health Workforce (COAT-PH) is an assessment of workforce foundational capabilities (FCs), based on the Foundational Public Health Services (FPHS) framework. The COAT-PH provides data on employees' capabilities to health departments to help them improve and operationalize the FPHS.

Implementation:
This article describes the development and pilot testing of the COAT-PH in a convenience sample of 8 health departments in Texas of various sizes and accreditation statuses. Participating leadership teams were provided easily interpretable reports to deliver clear evidence of division and organization-level workforce capability gaps and strengths. Follow-up semistructured interviews were conducted with leaders to capture insights into the tool and the usefulness of the findings.

Evaluation:
Eighty-eight percent of pilot health departments reported successfully appraising employee capability deficits, and 83% of small and medium health departments successfully assessed division or organizational FC strengths and gaps. All participating departments identified ways they could use their findings in future improvement efforts. Instrument psychometrics included the Cronbach α of internal reliability using a small test-retest sample (n = 6) of 0.956. Item test-retest reliability using Cohen's κ revealed 89% of items demonstrated at least slight reliability and 43% demonstrated moderate to substantial reliability. Content validity was established through review by 15 subject matter experts in the field of public health.

Discussion:
To provide the FPHS, health department leadership teams need a strong, prepared workforce and an effective method to demonstrate employee capabilities and provide evidence of health department workforce strengths and gaps to their governing bodies in the form of data that are clear and easy to understand. Early results demonstrated the usefulness of the COAT-PH in this effort.
The Juvenile Spondyloarthritis Disease Activity Index Is a Useful Tool in Enthesitis-Related Arthritis
Authors: Polat Merve Cansu , Ekici Tekin Zahide , Çelikel Elif , Güngörer Vildan , Kurt Tuba , Kaplan Melike Mehveş , Tekgöz Nilüfer , Sezer Müge , Karagöl Cüneyt , Coşkun Serkan , Öner Nimet , Sezer Serdar , Çelikel Acar Banu 
Published: July 2023

Objective
To compare enthesitis-related arthritis (ERA) patients with active and inactive disease at 6 months and define baseline predictors for disease inactivity. In addition, to evaluate the demographic, clinical, and laboratory characteristics of ERA patients and to identify the real-life impact of the Juvenile Spondyloarthritis Disease Activity Index (JSpADA) in predicting active disease in ERA.

Methods
This medical record review study was conducted with 56 patients who were diagnosed with ERA at our clinic between June 2009 and June 2022. Demographic and clinical characteristics, laboratory parameters, treatment, and JSpADA were recorded.

Results
The patients were divided into 2 groups as active (n = 34) and inactive (n = 22) according to their disease activity at month six. Sex, age at diagnosis, number and type of affected joints, and presence of sacroiliitis were similar in both groups. There was no difference in baseline erythrocyte sedimentation rate, but there was a significant difference in erythrocyte sedimentation rate at the third month (p = 0.52 and p = 0.018, respectively). The median JSpADA values at disease onset were 3.5 (interquartile range [IQR], 3.0–4.5) and 3.3 (IQR, 2.5–4.0) in the active and inactive groups, respectively (p = 0.27). At the third month, the median JSpADA values were 1.5 (IQR, 0.5–2.1) in the active group and 0.5 (IQR, 0.5–1.5) in the inactive group (p = 0.037). The cutoff value for JSpADA at the third month for active disease persisting at the month six was determined as 1 point (area under the curve, 0.662 ± 0.06; p = 0.042; 95% confidence interval, 0.51–0.80) by receiver operating characteristic curve analysis.

Conclusion
In ERA patients, a persistently high JSpADA value at follow-up is a predictive factor for active disease at the sixth month.
Congenital Midline Cervical Cleft and Thyroglossal Duct Fibrous Cord-Like, is There a Mixed Presentation?
Authors: Kruschewsky Leonardo de Souza , Matos Leandro Luongo de , Alonso Nivaldo , Seidler Cariline da Silva , Lisboa Sonyara Rauedys Oliveira , Silva Roberto Cintra Lomanto Santos , Goldenberg Dov Charles , Silva Tatiana Valeria Novais 
Published: July 2023

Introduction:
Congenital midline cervical cleft is a rare condition and is frequently misdiagnosed as thyroglossal duct cyst. Otherwise, the combination of congenital midline cervical cleft and thyroglossal duct fibrosis in the same patient is as rare as important to be registered with the intention to inform and offer specific managements details for the literature.

Case Presentation:
Eight-year-old boy with simultaneous congenital midline cervical cleft and a thyroglossal duct fibrosis. The anatomic, clinical, radiologic, and pathologic characteristics of the congenital midline cervical cleft are described as well as surgical technique for removal and repair with Z-plasty.

Conclusion:
Congenital midline cervical cleft is a rare condition and when diagnosed must be surgically treated as early as possible. Its differential diagnosis is a clinical challenge.
A Transcriptomic Approach to Understand Patient Susceptibility to Pneumonia After Abdominal Surgery
Authors: Torrance Hew D , Zhang Ping , Longbottom E Rebecca , Mi Yuxin , Whalley Justin P , Allcock Alice , Kwok Andrew J , Cano-Gamez Eddie , Geoghegan Cyndi G , Burnham Katie L , Antcliffe David B , Davenport Emma E , Pearse Rupert M , O’Dwyer Michael J , Hinds Charles J , Knight Julian C , Gordon Anthony C 
Published: July 2023

Objective:
To describe immune-pathways and gene-networks altered following major-abdominal surgery and identify transcriptomic patterns associated with postoperative pneumonia.

Summary Background Data:
Nosocomial infections are a major healthcare challenge, developing in over 20% of patients aged 45 or over undergoing major-abdominal surgery, with postoperative pneumonia associated with an almost five-fold increase in 30-day mortality.

Methods:
From a prospective consecutive cohort (n=150) undergoing major-abdominal surgery whole-blood RNA was collected preoperatively and at three time-points postoperatively (2-6, 24 and 48hrs). Twelve patients diagnosed with postoperative pneumonia and 27 matched patients remaining infection-free were identified for analysis with RNA-sequencing.

Results:
Compared to preoperative sampling, 3,639 genes were upregulated and 5,043 downregulated at 2-6hrs. Pathway-analysis demonstrated innate-immune activation with neutrophil-degranulation and Toll-like-receptor signalling upregulation alongside adaptive-immune suppression. Cell-type deconvolution of preoperative RNA-sequencing revealed elevated S100A8/9-high neutrophils alongside reduced naïve CD4 T-cells in those later developing pneumonia. Preoperatively, a gene-signature characteristic of neutrophil-degranulation was associated with postoperative pneumonia acquisition (P=0.00092). A previously reported Sepsis Response Signature (SRSq) score, reflecting neutrophil-dysfunction and a more dysregulated host response, at 48hrs postoperatively, differed between patients subsequently developing pneumonia and those remaining infection-free (P=0.045). Analysis of the novel neutrophil gene-signature and SRSq scores in independent major-abdominal surgery and polytrauma cohorts indicated good predictive performance in identifying patients suffering later infection.

Conclusions:
Major-abdominal surgery acutely upregulates innate-immune pathways while simultaneously suppressing adaptive-immune pathways. This is more prominent in patients developing postoperative pneumonia. Preoperative transcriptomic signatures characteristic of neutrophil-degranulation and postoperative SRSq scores may be useful predictors of subsequent pneumonia risk.
Brief PROMIS Assessment Screens for Frailty and Predicts Hospitalizations in Liver Transplant Candidates
Authors: Thuluvath Avesh J. , Duarte-Rojo Andres , Lai Jennifer C. , Peipert John , Dietch Zachary C. , Siddiqui Osama , Morrissey Sheila , Belfanti Kimberly , Zhao Lihui , Guo Kexin , Nizamuddin Mohammad , Polineni Praneet , Levitsky Josh , Flores Ann-Marie , Ladner Daniela P. 
Published: July 2023

Background.
Frailty is prevalent in patients with end-stage liver disease and predicts waitlist mortality, posttransplant mortality, and frequency of hospitalizations. The Liver Frailty Index (LFI) is a validated measure of frailty in liver transplant (LT) candidates but requires an in-person assessment.

Methods.
We studied the association between patient-reported physical function and LFI in a single-center prospective study of adult patients with cirrhosis undergoing LT evaluation from October 2020 to December 2021. Frailty was assessed with the LFI and 4-m gait speed. Patient-reported physical function was evaluated using a brief Patient-Reported Outcomes Measurement Information System (PROMIS) survey.

Results.
Eighty-one LT candidates were enrolled, with a mean model of end-stage liver disease–sodium of 17.6 (±6.3). The mean LFI was 3.7 (±0.77; 15% frail and 59% prefrail) and the mean PROMIS Physical Function score was 45 (±8.6). PROMIS Physical Function correlated with LFI (r = –0.54, P < 0.001) and 4-m gait speed (r = 0.48, P < 0.001). The mean hospitalization rate was 1.1 d admitted per month. After adjusting for age, sex, and model of end-stage liver disease–sodium, patient-reported physical function–predicted hospitalization rate (P = 0.001).

Conclusions.
This study suggests that a brief patient-reported outcome measure can be used to screen for frailty and predict hospitalizations in patients with cirrhosis.
Hyperexcitability and translational phenotypes in a preclinical model ofSYNGAP1mutations
Authors: Fenton Timothy A , Haouchine Olivia Y , Hallam Elizabeth L , Smith Emily M , Jackson Kiya C. , Rahbarian Darlene , Canales Cesar , Adhikari Anna , Nord Alexander S. , Ben-Shalom Roy , Silverman Jill L 
Published: July 2023

AbstractSYNGAP1is a critical gene for neuronal development, synaptic structure, and function. Although rare, the disruption ofSYNGAP1directly causes a genetically identifiable neurodevelopmental disorder (NDD) called SYNGAP1-related intellectual disability. Without functional SynGAP1 protein, patients present with intellectual disability, motor impairments, and epilepsy. Previous work using mouse models with a variety of germline and conditional mutations has helped delineate SynGAP1’s critical roles in neuronal structure and function, as well as key biochemical signaling pathways essential to synapse integrity.Homozygous loss ofSYNGAP1is embryonically lethal. Heterozygous mutations ofSynGAP1result in a broad range of phenotypes including increased locomotor activity, impaired working spatial memory, impaired cued fear memory, and increased stereotypic behavior. Ourin vivofunctional data, using the original germline mutation mouse line from the Huganir laboratory, corroborated robust hyperactivity and learning and memory deficits. Here, we describe impairments in the translational biomarker domain of sleep, characterized using neurophysiological data collected with wireless telemetric electroencephalography (EEG). We discoveredSyngap1+/-mice exhibited elevated spike trains in both number and duration, in addition to elevated power, most notably in the delta power band. Primary neurons fromSyngap1+/-mice displayed increased network firing activity, greater spikes per burst, and shorter inter-burst intervals between peaks using high density micro-electrode arrays (HD-MEA). This work is translational, innovative, and highly significant as it outlines functional impairments inSyngap1mutant mice. Simultaneously, the work utilized untethered, wireless neurophysiology that can discover potential biomarkers of Syngap1R-ID, for clinical trials, as it has done with other NDDs. Our work is substantial forward progress toward translational work for SynGAP1R-ID as it bridgesin-vitroelectrophysiological neuronal activity and function within vivoneurophysiological brain activity and function. These data elucidate multiple quantitative, translational biomarkersin vivoandin vitrofor the development of treatments for SYNGAP1-related intellectual disability.