bluuebunny/crossref_metadata_2025_split huggingface dataset:
TWEAK/FN14 promotes profibrogenic pathway activation in Prominin-1-expressing hepatic progenitor cells in biliary atresia
Authors: Short Celia , Zhong Allen , Xu Jiabo , Mahdi Elaa , Glazier Alison , Malkoff Nicolas , Noriega Nicolas , Yeo Theresa , Asahina Kinji , Wang Kasper S. 
Published: March 2023

Background and Aims:
Biliary atresia (BA), a congenital cholestatic liver disease, commonly culminates in end-stage liver disease. We previously demonstrated in BA that Prominin-1 (Prom1)-expressing hepatic progenitor cells (HPCs) expand within regions of developing fibrosis, giving rise to cholangiocytes within biliary ductular reactions. Null mutation of Prom1 or ablation of cells expressing Prom1 significantly diminishes fibrogenesis. FN14, the receptor for TNF-like weak inducer of apoptosis (TWEAK), is expressed by HPCs. TWEAK/FN14 signaling promotes fibrosis in multiple organ systems. Therefore, we hypothesized that TWEAK/FN14 signaling mediates Prom1-expressing HPC proliferation leading to profibrogenic ductular reactions in BA.

Approach and Results:
The experimental mouse model of BA mediated by perinatal rhesus rotavirus (RRV) infection resulted in increased co-expression of Fn14 in Prom1-expressing HPCs within regions of ductular reactions. FN14 antagonist L524-0366 decreased ductular reactions, biliary fibrosis and periportal fibroblast activation in RRV injury. L524-0366 inhibition also demonstrated loss of downstream noncanonical NF-kB signaling expression in RRV injury. Murine HPC organoids demonstrated accelerated organoid growth and proliferation when treated with recombinant TWEAK. Increased organoid proliferation with recombinant TWEAK was lost when also treated with L524-0366. Analysis of a large publicly available RNA sequencing database of BA and normal control patients revealed significant increases in expression of PROM1, FN14, and genes downstream of TNF signaling and noncanonical NF-κB signaling pathways in BA infants. Infants who failed to achieve bile drainage after hepatoportoenterostomy had higher relative levels of FN14 expression.

Conclusion:
TWEAK/FN14 signaling activation in Prom1-expressing HPCs contributes to proliferation of profibrogenic ductular reactions in BA.
HBV with precore and basal core promoter mutations exhibits a high replication phenotype and causes ER stress-mediated cell death in humanized liver chimeric mice
Authors: Uchida Takuro , Imamura Michio , Hayes C. Nelson , Suehiro Yosuke , Teraoka Yuji , Ohya Kazuki , Aikata Hiroshi , Abe-Chayama Hiromi , Ishida Yuji , Tateno Chise , Hara Yuichi , Hino Keisuke , Okamoto Toru , Matsuura Yoshiharu , Aizaki Hideki , Wake Kenjiro , Kohara Michinori , Liang T. Jake , Oka Shiro , Chayama Kazuaki 
Published: March 2023

Background and Aims:
Mutations within the precore (PC) and basal core promoter (BCP) regions of the HBV genome are associated with fulminant hepatitis and HBV reactivation. These mutations may enhance viral replication, but little is known about whether they directly induce damage to the liver. We investigated mechanisms of direct cytopathic effects induced by the infection with PC/BCP mutants in the absence of immune response in vitro and in vivo.

Approach and Results:
Mice with humanized livers and hepatocytes derived from humanized mice were infected with either wild-type or mutant-type PC/BCP HBV, and the HBV replication and human hepatocyte damage were evaluated. HBV proliferated vigorously in mice with PC/BCP-mutant infection, and the severe loss of human hepatocytes with a slight human ALT elevation subsequently occurred only in PC/BCP mutant mice. In PC/BCP mutant infection, the accumulation of HBsAg in humanized livers colocalized with the endoplasmic reticulum, leading to apoptosis through unfolded protein response in HBV-infected hepatocytes. RNA-sequencing revealed the molecular characteristics of the phenotype of PC/BCP mutant infection in a humanized mouse model. Reduced ALT elevation and higher HBV DNA levels in this model are consistent with characteristics of HBV reactivation, indicating that the hepatocyte damage in this model might mimic HBV reactivation followed by hepatocyte damage under immunosuppressive conditions.

Conclusion:
PC and BCP mutations were associated with enhanced viral replication and cell death induced by ER stress using HBV infection models. These mutations might be associated with liver damage in patients with fulminant hepatitis or HBV reactivation.
Quantifying the benefit of nonselective beta-blockers in the prevention of hepatic decompensation: A Bayesian reanalysis of the PREDESCI trial
Authors: Rowe Ian A. , Villanueva Càndid , Shearer Jessica E. , Torres Ferran , Albillos Agustín , Genescà Joan , Garcia-Pagan Joan C. , Tripathi Dhiraj , Hayes Peter C. , Bosch Jaume , Abraldes Juan G. ,   for the PREDESCI trial investigators
Published: March 2023

Background and Aims:
Beta-blockers have been studied for the prevention of variceal bleeding and, more recently, for the prevention of all-cause decompensation. Some uncertainties regarding the benefit of beta-blockers for the prevention of decompensation remain. Bayesian analyses enhance the interpretation of trials. The purpose of this study was to provide clinically meaningful estimates of both the probability and magnitude of the benefit of beta-blocker treatment across a range of patient types.

Approach and Results:
We undertook a Bayesian reanalysis of PREDESCI incorporating 3 priors (moderate neutral, moderate optimistic, and weak pessimistic). The probability of clinical benefit was assessed considering the prevention of all-cause decompensation. Microsimulation analyses were done to determine the magnitude of the benefit. In the Bayesian analysis, the probability that beta-blockers reduce all-cause decompensation was >0.93 for all priors. The Bayesian posterior hazard ratios (HR) for decompensation ranged from 0.50 (optimistic prior, 95% credible interval 0.27–0.93) to 0.70 (neutral prior, 95% credible interval 0.44–1.12). Exploring the benefit of treatment using microsimulation highlights substantial treatment benefits. For the neutral prior derived posterior HR and a 5% annual incidence of decompensation, at 10 years, an average of 497 decompensation-free years per 1000 patients were gained with treatment. In contrast, at 10 years 1639 years per 1000 patients were gained from the optimistic prior derived posterior HR and a 10% incidence of decompensation.

Conclusions:
Beta-blocker treatment is associated with a high probability of clinical benefit. This likely translates to a substantial gain in decompensation-free life years at the population level.
Short-chain acyl-CoA dehydrogenase is a potential target for the treatment of vascular remodelling
Authors: Zhong Xiaoyi , Li Zhonghong , Xu Qingping , Peng Huan , Su Yongshao , Le Kang , Shu Zhaohui , Liao Yingqin , Ma Zhichao , Pan Xuediao , Xu Suowen , Zhou Sigui 
Published: March 2023

Objectives:
Short-chain acyl-CoA dehydrogenase (SCAD), a key enzyme in the fatty acid oxidation process, is not only involved in ATP synthesis but also regulates the production of mitochondrial reactive oxygen species (ROS) and nitric oxide synthesis. The purpose of this study was to investigate the possible role of SCAD in hypertension-associated vascular remodelling.

Methods:
In-vivo experiments were performed on spontaneously hypertensive rats (SHRs, ages of 4 weeks to 20 months) and SCAD knockout mice. The aorta sections of hypertensive patients were used for measurement of SCAD expression. In-vitro experiments with t-butylhydroperoxide (tBHP), SCAD siRNA, adenovirus-SCAD (MOI 90) or shear stress (4, 15 dynes/cm2) were performed using human umbilical vein endothelial cells (HUVECs).

Results:
Compared with age-matched Wistar rats, aortic SCAD expression decreased gradually in SHRs with age. In addition, aerobic exercise training for 8 weeks could significantly increase SCAD expression and enzyme activity in the aortas of SHRs while decreasing vascular remodelling in SHRs. SCAD knockout mice also exhibited aggravated vascular remodelling and cardiovascular dysfunction. Likewise, SCAD expression was also decreased in tBHP-induced endothelial cell apoptosis models and the aortas of hypertensive patients. SCAD siRNA caused HUVEC apoptosis in vitro, whereas adenovirus-mediated SCAD overexpression (Ad-SCAD) protected against HUVEC apoptosis. Furthermore, SCAD expression was decreased in HUVECs exposed to low shear stress (4 dynes/cm2) and increased in HUVECs exposed to 15 dynes/cm2 compared with those under static conditions.

Conclusion:
SCAD is a negative regulator of vascular remodelling and may represent a novel therapeutic target for vascular remodelling.

Supplemental Graphical abstract:

http://links.lww.com/HJH/C151
Impact of atrial fibrillation on the accuracy of oscillometric blood pressure monitoring in ICU patients from a large real-world database
Authors: Li Yuxi , Wang Beining , Fan Fangfang , Weng Haoyu , Zhang Long , Jiang Jie , Zheng Bo , Zhang Yan , Li Jianping 
Published: March 2023

Objectives:
Oscillometric blood pressure (BP) measurement in atrial fibrillation patients is controversial due to stroke volume variation. Here, we performed a cross-sectional study to investigate the impact of atrial fibrillation on the accuracy of oscillometric BP in the ICU setting.

Methods:
Adult patients with atrial fibrillation or sinus rhythm records were enrolled from Medical Information Mart for Intensive Care-III database. Concurrently recorded noninvasive oscillometric BPs (NIBPs) and intra-arterial BPs (IBPs) were classified as atrial fibrillation or sinus rhythm group according to heart rhythm. Bland–Altmann plots assessed bias and limits of agreement of NIBP to IBP. Pairwise comparison was performed on NIBP/IBP bias between atrial fibrillation and sinus rhythm. Linear mixed-effect model was used to assess the impact of heart rhythm on NIBP/IBP bias after adjusting confounders.

Results:
Two thousand, three hundred and thirty-five patients (71.95 ± 11.23 years old, 60.90% were men) were included. Systolic, diastolic, and mean NIBP/IBP biases were not clinically different between atrial fibrillation and sinus rhythm circumstances (SBP bias: 0.66 vs. 1.21 mmHg, P = 0.002; DBP: −5.29 vs. −5.17, P = 0.1; mean BP: −4.45 vs. −4.19, P = 0.01). After adjusting for age, sex, heart rate, arterial BP, and vasopressor usage, the effect of heart rhythm on NIBP/IBP bias was within ±5 mmHg for SBP and DBP [effect on SBP bias: 3.32 mmHg (95% confidence interval (CI) 2.89–3.74), P < 0.001; DBP: −0.89 (−1.17 to −0.60), P < 0.001], while the effect on mean BP bias was not significant [0.18 mmHg (−0.10 to 0.46), P = 0.2].

Conclusion:
Atrial fibrillation would not influence the agreement of oscillometric BP to IBP in ICU patients compared with sinus rhythm.
A qualitative study of patients’ and carers’ perspectives on factors influencing access to hypertension care and compliance with treatment in Nigeria
Authors: Ukoha-Kalu Blessing O. , Adibe Maxwell O. , Ukwe Chinwe V. 
Published: March 2023

Objective:
We explored patients’ and carers’ perspectives on factors influencing access to hypertension care and compliance with treatment.

Methods:
This was a qualitative study using in-depth interviews with hypertensive patients and/or family carers receiving care at a government-owned hospital in north-central Nigeria. Eligible participants were patients who had hypertension, receiving care in the study setting, were aged 55 years and over and had given their written/thumbprint consent to participate in the study. An interview topic guide was developed from the literature and through pretesting. All the interviews were held face-to-face by a member of the research team. This study was conducted between December 2019 and February 2020. NVivo version 12 was used to analyse the data.

Results:
A total of 25 patients and 13 family carers participated in this study. To understand the barriers to compliance with hypertension self-management practices, three themes were explored, namely: personal factors, family/societal factors and clinic/organization factors. Support was the key enabling factor for self-management practices, which were categorized to emerge from three sources namely: family members, community and government. Participants reported that they do not receive lifestyle management advice from healthcare professionals, and do not know the importance of eating low-salt diets/engaging in physical activities.

Conclusion:
Our findings show that study participants had little or no awareness of hypertension self-management practices. Providing financial support, free educational seminars, free blood pressure checks, and free medical care for the elderly could improve hypertension self-management practices among patients living with hypertension.
Deep Learning-Based Classification of Subtypes of Primary Angle-Closure Disease With Anterior Segment Optical Coherence Tomography
Authors: Eslami Yadollah , Mousavi Kouzahkanan Zahra , Farzinvash Zahra , Safizadeh Mona , Zarei Reza , Fakhraie Ghasem , Vahedian Zakieh , Mahmoudi Tahereh , Fadakar Kaveh , Beikmarzehei Alireza , Tabatabaei Seyed Mehdi 
Published: March 2023

Précis:
We developed a deep learning-based classifier that can discriminate primary angle closure suspects (PACS), primary angle closure (PAC)/primary angle closure glaucoma (PACG), and also control eyes with open angle with acceptable accuracy.

Purpose:
To develop a deep learning-based classifier for differentiating subtypes of primary angle closure disease, including PACS and PAC/PACG, and also normal control eyes.

Materials and Methods:
Anterior segment optical coherence tomography images were used for analysis with 5 different networks including MnasNet, MobileNet, ResNet18, ResNet50, and EfficientNet. The data set was split with randomization performed at the patient level into a training plus validation set (85%), and a test data set (15%). Then 4-fold cross-validation was used to train the model. In each mentioned architecture, the networks were trained with original and cropped images. Also, the analyses were carried out for single images and images grouped on the patient level (case-based). Then majority voting was applied to the determination of the final prediction.

Results:
A total of 1616 images of normal eyes (87 eyes), 1055 images of PACS (66 eyes), and 1076 images of PAC/PACG (66 eyes) eyes were included in the analysis. The mean ± SD age was 51.76 ± 15.15 years and 48.3% were males. MobileNet had the best performance in the model, in which both original and cropped images were used. The accuracy of MobileNet for detecting normal, PACS, and PAC/PACG eyes was 0.99 ± 0.00, 0.77 ± 0.02, and 0.77 ± 0.03, respectively. By running MobileNet in a case-based classification approach, the accuracy improved and reached 0.95 ± 0.03, 0.83 ± 0.06, and 0.81 ± 0.05, respectively. For detecting the open angle, PACS, and PAC/PACG, the MobileNet classifier achieved an area under the curve of 1, 0.906, and 0.872, respectively, on the test data set.

Conclusion:
The MobileNet-based classifier can detect normal, PACS, and PAC/PACG eyes with acceptable accuracy based on anterior segment optical coherence tomography images.
Retinal Nerve Fiber Layer Defect Associated With Progressive Myopia
Authors: Song Ji Eun , Wy Seoyoung , Kim Ji-Ah , Lee Eun Ji 
Published: March 2023

Purpose:
The purpose of this study was to report a case with bilateral paravascular inner retinal defects (PIRDs) enlarging with progressive myopia, which had different structural characteristics from the glaucomatous retinal nerve fiber layer (RNFL) defect.

Patients and Methods:
A 10-year-old girl with high myopia was referred to a glaucoma clinic for evaluation of RNFL defects shown in color fundus photographs. Fundus photographs and optical coherence tomography examinations were serially reviewed to examine the changes in the RNFL.

Results:
Cleavage of inner retinal layers involving the layers deeper than the RNFL was identified in optical coherence tomography, which appeared and enlarged in both eyes along with progressive myopia and axial elongation during the follow-up period of 8 years.

Conclusions:
PIRD developed and enlarged with progressive myopia and axial elongation in childhood. It should be differentiated from the widening of RNFL defect shown with glaucoma progression.
High-Throughput Drug Screening on Borrelia garinii and Borrelia afzelii Identified Hypocrellin A as an Active Drug Candidate Against Borrelia Species
Authors: Li Tingting , Xin Yuxian , Liu Dongxia , Sun Jingrong , Li Jingwei , Zhang Ying , Feng Jie 
Published: March 2023

Abstract
Lyme disease (LD) is a tick-transmitted infection caused by Borrelia burgdorferi sensu lato species, which include B. burgdorferi, Borrelia afzelii and Borrelia garinii. The majority of patients with early LD can be cured by the standard treatment, yet some still suffer from posttreatment LD syndrome. The presence of Borrelia persisters has been proposed as a contributing factor, because they cannot be completely eradicated by the currently used antibiotics for LD. Finding new pharmaceuticals targeting Borrelia persisters is crucial for developing more effective treatments. Here, we first confirmed the existence of persisters in B. garinii and B. afzelii cultures and then conducted a high-throughput screening of a custom drug library against persister-rich stationary-phase B. garinii and B. afzelii cultures. Among 2427 compounds screened, hypocrellin A (HA), anthracycline class of drugs and topical antibiotics along with some other natural compounds were identified to have strong potential for killing persisters of B. garinii and B. afzelii. HA was the most active anti-Borrelia compound, capable of eradicating stationary-phase Borrelia persisters, in particular when combined with doxycycline and/or ceftriaxone. Liposoluble antioxidant vitamin E was found to antagonize the activity of HA, indicating HA’s target is the cell membrane where HA triggers the generation of reactive oxygen species in the presence of light. HA was found to have distinct bactericidal activity against Borrelia species but had poor or no activity against gram-positive and gram-negative bacteria. Identification of the abovementioned drug candidates may help develop more effective therapies for LD.
Sense of Security Mediates the Relationship Between Self-care Behavior and Health Status of Patients With Heart Failure
Authors: Ingadottir Brynja , Jaarsma Tiny , Norland Kristján , Ketilsdóttir Auður 
Published: March 2023

Background
Promoting patients' sense of security is among the goals of nursing care within heart failure management.

Objective
The aim of this study was to examine the role of sense of security in the relationship between self-care behavior and health status of patients with heart failure.

Methods
Patients recruited from a heart failure clinic in Iceland answered a questionnaire about their self-care (European Heart Failure Self-care Behavior Scale; possible scores, 0–100), their sense of security (Sense of Security in Care–Patients' Evaluation; possible scores, 1–100), and their health status (Kansas City Cardiomyopathy Questionnaire, including symptoms, physical limitations, quality of life, social limitations, and self-efficacy domains; possible scores, 0–100). Clinical data were extracted from electronic patient records. Regression analysis was used to examine the mediation effect of sense of security on the relationship between self-care and health status.

Results
The patients (N = 220; mean [SD] age, 73.6 [13.8] years; 70% male, 49% in New York Heart Association functional class III) reported a high sense of security (mean [SD], 83.2 [15.2]) and inadequate self-care (mean [SD], 57.2 [22.0]); their health status, as assessed by all domains of the Kansas City Cardiomyopathy Questionnaire, was fair to good except for self-efficacy, which was good to excellent. Self-care was associated with health status (P < .01) and sense of security (P < .001). Regression analysis confirmed the mediating effect of sense of security on the relationship between self-care and health status.

Conclusions
Sense of security in patients with heart failure is an important part of daily life and contributes to better health status. Heart failure management should not only support self-care but also aim to strengthen sense of security through positive care interaction (provider-patient communication) and the promotion of patients' self-efficacy, and by facilitating access to care.
Application of a new frailty care model
Authors: Siegmund Lee Anne , Novosel Lorraine 
Published: March 2023

ABSTRACT
Frailty is an age-related physiological deterioration that results in weakness, slowness of movement, fatigue, weight loss, and multimorbidity. These limitations lead to an inability to respond to stressors, which ultimately increase risk for poor outcomes including falls, disability, hospitalization, and mortality. Although many medical and physiology-based frailty screening tools and associated theories exist, none are specific to advanced practice nurses and the care of the older adult. For this reason, the authors present the case of a frail older adult and the application of the Frailty Care Model. The authors developed the Frailty Care Model which illustrates a theory that states: Frailty is a fluid condition of aging that will respond to interventions and will progress in the absence of interventions. It is an evidence-based model that helps the nurse practitioner (NP) screen for frailty; apply important nutritional, psychosocial, and physical frailty interventions; and evaluate the care provided to the older adult. The purpose of this article is to present the case of Maria, an 82-year-old woman with frailty, and demonstrate how the NP can apply the Frailty Care Model to inform care of the older adult. The Frailty Care Model is designed so that it can be easily integrated into the workflow of the medical encounter and require little additional time or resources. This case study describes specific examples of using the model to avoid, stabilize, and reverse frailty.
Effects of acupuncture and pelvic floor muscle training on bladder dysfunction after spinal cord injury: A meta-analysis
Authors: Zang Y.T. , Bai M.J. , Wang L. , Zhang M.X. , Li L. 
Published: March 2023

Objective:
We aimed to systematically review and quantify the association between acupuncture and pelvic floor muscle exercise and bladder dysfunction rehabilitation in individuals with spinal nerve injury.

Methods:
A meta-analysis was conducted using an evidence-based nursing analysis method based on clinical evidence. China National Knowledge Infrastructure, PubMed, VIP database, Wan Fang database, Cochrane Library, and other databases were searched by computer from January 1, 2000 to January 1, 2021. The literature was searched for clinical randomized controlled trials on acupuncture stimulation, pelvic floor muscle function training, and bladder function recovery training after spinal cord nerve injury. Two reviewers independently used The Cochrane Collaboration recommended randomized controlled trial risk of bias assessment tool to evaluate the quality of the literature. Then, the meta-analysis was performed using RevMan 5.3 software.

Results:
A total of 20 studies were included, with a total sample size of 1468 cases, including 734 patients in the control group and 734 patients in the experimental group. The results of our meta-analysis showed that acupuncture treatment [OR = 3.98, 95% CI (2.77, 5.72), Z = 7.49, P < .001] and pelvic floor muscle treatment [OR = 7.63, 95% CI (4.47, 13.04), Z = 7.45, P < .001] was statistically significant.

Conclusion:
Acupuncture and pelvic floor muscle exercise are effective intervention and treatment methods, which have obvious effects on rehabilitation treatment of bladder dysfunction after spinal nerve injury.