bluuebunny/crossref_metadata_2025_split huggingface dataset:
Toll‐like receptor‐2 in cardiomyocytes and macrophages mediates isoproterenol‐induced cardiac inflammation and remodeling
Authors: Qian Jinfu , Liang Shiqi , Wang Qinyan , Xu Jiachen , Huang Weijian , Wu Gaojun , Liang Guang 
Published: December 2022

AbstractHeart failure (HF) is the leading cause of morbidity and mortality worldwide. Activation of the innate immune system initiates an inflammatory response during cardiac remodeling induced by isoproterenol (ISO). Here, we investigated whether Toll‐like receptor‐2 (TLR2) mediates ISO‐induced inflammation, hypertrophy, and fibrosis. TLR2 was found to be increased in the heart tissues of mouse with HF under ISO challenge. Further, cardiomyocytes and macrophages were identified as the main cellular sources of the increased TLR2 levels in the model under ISO stimulation. The effect of TLR2 deficiency on ISO‐induced cardiac remodeling was determined using TLR2 knockout mice and bone marrow transplantation models. In vitro studies involving ISO‐treated cultured cardiomyocytes and macrophages showed that TLR2 knockdown significantly decreased ISO‐induced cell inflammation and remodeling via MAPKs/NF‐κB signaling. Mechanistically, ISO significantly increased the TLR2‐MyD88 interaction in the above cells in a TLR1‐dependent manner. Finally, DAMPs, such as HSP70 and fibronectin 1 (FN1), were found to be released from the cells under ISO stimulation, which further activated TLR1/2‐Myd88 signaling and subsequently activated pro‐inflammatory cytokine expression and cardiac remodeling. In summary, our findings suggest that TLR2 may be a target for the alleviation of chronic adrenergic stimulation‐associated HF. In addition, this paper points out the possibility of TLR2 as a new target for heart failure under ISO stimulation.
Entrustable Professional Activities for the Training of Postgraduate Primary Care Pediatricians
Authors: Villaizán Pérez Carmen , Aparicio Rodrigo María , Kovacs Akos , Barak Shimon , Calamita Patrizia , Dejak Gornik Katja , Jaeger-Roman Elke , Kartousova Beata , Katz Manuel , Rafele Innocenza , Reali Laura , Reingold Stephen , Sauseng Werner , Fehr Folkert 
Published: December 2022

Problem
Competency-based training is a model of medical education program that uses an organized framework of competencies to develop entrustable professional activities (EPAs) for each specialty. Implementation of EPAs varies by medical specialty and country. Although national models for primary care pediatrics have been suggested in the past, standardized EPAs have not been established.

Approach
The authors, all members of the curriculum working group of the European Confederation of Primary Care Paediatricians, describe the development and design of a training model based on EPAs specifically for pediatricians in primary care. The objective was to facilitate and disseminate a training model that standardizes and improves training in primary care pediatrics. They aimed to make the model flexible enough so that it can be adapted to different training models and different European health systems.

Outcomes
Between May 2017 and December 2019, the authors developed a framework that includes 7 domains of competencies for the training in pediatric primary care and a set of 11 core EPAs to guide the learning process. They structured each EPA as follows: title, activity profile, domains of competence, competencies within each domain, required knowledge and skills, learning objectives described in terms of outcomes, and a 3-stage rating supervision scale to evaluate the level of performance.

Next Steps
The next step is the progressive implementation of these EPAs into the postgraduate primary care pediatrics training programs of European health systems. To support this implementation, the authors intend to develop training videos to assist in daily teaching of the EPAs. The authors will also develop a pan-European online resident forum designed specifically to facilitate EPA learning by sharing and discussing clinical cases. They plan to launch a pilot study on the use of the EPAs in primary care health centers in 6 European countries.
From surgery to endoscopy: the evolution of the bariatric discipline
Authors: Wei Yongqiu , Li Peng , Zhang Shutian 
Published: December 2022

Abstract
Obesity, with its increasing morbidity and prevalence, is now a worldwide public health problem. Obesity and its related comorbidities impose a heavy burden on societal health and the economy. The practice of bariatric surgery has evolved from its early surgical procedures, many of which are no longer routine operations. With clinical practice, research, and experience, bariatric surgery has gradually become an important last resort for the control of weight and obesity-related metabolic diseases in moderately and severely obese patients. However, there is still room for further improvements in bariatric surgical procedures, especially with regard to long-term issues and complications. Endoscopic weight loss technology has developed rapidly in recent years. The advantages of this technology include minimal invasiveness, an obvious weight loss effect, and few complications, thus filling the gap between medications and lifestyle adjustments and surgical treatment of obesity. Endoscopic weight loss technology may even replace surgical bariatric procedures. This review summarized the current status of bariatric metabolic surgery and newly developed bariatric endoscopic procedures.
Adrenomedullin in paraventricular nucleus attenuates adipose afferent reflex and sympathoexcitation via receptors mediated nitric oxide–gamma-aminobutyric acid A type receptor pathway in rats with obesity-related hypertension
Authors: Wang Fang-Zheng , Qian Pei , Liu Mu-Yue , Ding Lei , Wang Hong-Yu , Wang Qian , Ding Zi-Yang , Jin Fei-Yu , Li Rui-Gang , Zhou Ye-Bo 
Published: December 2022

Background:
Hypothalamic paraventricular nucleus (PVN) is an important central site for the control of the adipose afferent reflex (AAR) that increases sympathetic outflow and blood pressure in obesity-related hypertension (OH).

Method:
In this study, we investigated the effects of nitric oxide (NO) and cardiovascular bioactive polypeptide adrenomedullin (ADM) in the PVN on AAR and sympathetic nerve activity (SNA) in OH rats induced by a high-fat diet.

Results:
The results showed that ADM, total neuronal NO synthase (nNOS) and phosphorylated-nNOS protein expression levels in the PVN of the OH rats were down-regulated compared to the control rats. The enhanced AAR in OH rats was attenuated by PVN acute application of NO donor sodium nitroprusside (SNP), but was strengthened by the nNOS inhibitor nNOS-I, guanylyl cyclase inhibitor (1H-[1,2,4]Oxadiazolo[4,3-a]quinoxalin-1-one, ODQ) and gamma-aminobutyric acid A type receptor (GABAA) antagonist Bicuculline. Moreover, PVN ADM microinjection not only decreased basal SNA but also attenuated the enhanced AAR in OH rats, which were effectively inhibited by ADM receptor antagonist ADM22–52, nNOS-I, ODQ or Bicuculline pretreatment. Bilateral PVN acute microinjection of ADM also caused greater increases in NO and cyclic guanosine monophosphate (cGMP) levels, and nNOS phosphorylation. Adeno-associated virus vectors encoding ADM (AAV-ADM) transfection in the PVN of OH rats not only decreased the elevated AAR, basal SNA and blood pressure (BP), but also increased the expression and activation of nNOS. Furthermore, AAV-ADM transfection improved vascular remodeling in OH rats.

Conclusion:
Taken together, our data highlight the roles of ADM in improving sympathetic overactivation, enhanced AAR and hypertension, and its related mechanisms associated with receptors mediated NO–cGMP–GABAA pathway in OH condition.
Reproductive Safety of Trazodone After Maternal Exposure in Early Pregnancy
Authors: Dao Kim , Shechtman Svetlana , Diav-Citrin Orna , George Nathan , Richardson Jonathan Luke , Rollason Victoria , Pistelli Alessandra , Eleftheriou Georgios , Berlin Maya , Ekobena Pierre , Rousson Valentin , Addor Marie-Claude , Baud David , Buclin Thierry , Panchaud Alice , Winterfeld Ursula 
Published: December 2022

Abstract

Purpose/Background
Trazodone is indicated for the treatment of major depressive disorder, but more frequently prescribed off-label at lower doses for insomnia in women of childbearing age. The aim of this study was to assess the risks linked to trazodone exposure during pregnancy for which limited safety data are available.

Methods/Procedures
This multicenter, observational prospective cohort study compared pregnancy outcomes in women exposed to trazodone in early pregnancy against those in a reference group of women exposed to a selective serotonin reuptake inhibitors (SSRIs) between 1996 and 2021.

Findings/Results
The sample included 221 trazodone and 869 SSRI-exposed pregnancies. Exposure to trazodone in the first trimester was not associated with a significant difference in the risk of major congenital anomalies (trazodone [1/169, 0.6%]; SSRI [19/730, 2.6%]; adjusted odds ratio, 0.2; 95% confidence interval, 0.03–1.77). The cumulative incidences of live birth were 61% and 73% in the trazodone and reference group, respectively (25% vs 18% for pregnancy loss and 14% vs 10% for pregnancy termination). Trazodone exposure was not associated with a significantly increased risk of pregnancy termination and pregnancy loss. The rate of small for gestational age infants did not differ between the groups.

Implications/Conclusions
This study did not reveal a significant difference in the risk of major congenital anomalies after first trimester exposure to trazodone, compared with SSRI exposure. Although this study is the largest so far, these results call for confirmation through further studies.
A Structured Rounding Proforma in the Hyper Acute Stroke Unit (HASU): A Quality Improvement Project
Authors: Ludley Alistair , Bahk Anna , Al-Shihabi Ahmed 
Published: December 2022

ABSTRACT
Strokes affect 100,000 patients annually in the United Kingdom. These patients are often complex and require multidisciplinary team input, hence why they are often treated within dedicated and highly specialized “hyper acute stroke units”. However, such specialist care can prove challenging to recently qualified or more junior doctors, who may miss pertinent aspects of the history or examination within the daily patient rounding documentation. Building on evidence-based practice using structured rounds and checklists, this quality improvement aimed to improve adherence of documentation for 20 predetermined key components of a stroke round by introducing a structured daily stroke rounding proforma. Adherence to documentation for the 20 components improved with the introduction of the stroke rounding proforma, with seven components demonstrating statistically significant positive changes in documentation rates, p < .05. Qualitative feedback was collected to aid in the development and acceptability of the proforma. Our study concluded a structured daily stroke rounding proforma can improve adherence to documentation in stroke care. Chiefly, the proforma was of greatest benefit to junior members of the medical team, particularly as an aid memoire.
Transcriptome analysis of the impact of diabetes as a comorbidity on tuberculosis
Authors: Liu Tao , Wang Yaguo , Gui Jing , Fu Yu , Ye Chunli , Hong Xiangya , Chen Ling , Li Yuhua , Zhang Xilin , Hong Wenxu 
Published: December 2022

Background:
Diabetes mellitus patients with pulmonary tuberculosis (DMTB) comorbidity has been recognized as a major obstacle towards achieving the World Health Organization goal of reducing the tuberculosis incidence rate by 90% in 2035. Host immune responses affected by diabetes can lead to increased susceptibility, severity and poor treatment outcomes in DMTB patients, and the underlying mechanisms have not yet been fully elucidated. This study aimed to identify key immunological and cellular components that contribute to increased morbidity and mortality in DMTB cases.

Methods:
We performed RNA-Seq of total RNA isolated from peripheral blood mononuclear cells from 3 TB, 3 diabetes mellitus, and 3 DMTB patients and healthy controls, and analyzed differential expression, pathway enrichment and clustering of differentially-expressed genes (DEGs) to identify biological pathways altered specifically in DMTB patients.

Results:
Bioinformatic analysis of DEGs suggested that enhanced inflammatory responses, small GTPases, the protein kinase C signaling pathway, hemostasis and the cell cycle pathway are likely implicated in the pathogenesis of the DMTB comorbidity.

Conclusion:
The DMTB comorbidity is associated with an altered transcriptome and changes in various biological pathways. Our study provides new insights on the pathological mechanism that may aid the development of host-directed therapies for this increasingly prevalent disease in high TB burden countries.
Clinical efficacy of moluodan in the treatment of chronic atrophic gastritis: A protocol for systematic review and meta-analysis
Authors: Yu Yunfeng , Yang Xinyu , Hu Gang , Yin Shuang , Zhang Fei , Wen Yandong , Zhu Ying , Liu Zhenjie 
Published: December 2022

Background:
Chronic atrophic gastritis (CAG) is an important stage of precancerous lesions of gastric cancer, and also a key period of drug intervention. However, there is still a lack of drugs to maintain the treatment of CAG until the advent of moluodan.

Objective:
This study was conducted to assess the clinical efficacy of moluodan in the treatment of CAG by meta-analysis and trial sequential analysis.

Methods:
China National Knowledge Infrastructure, China Biology Medicine, VIP, Wanfang, Embase, PubMed, the Cochrane Library, and Web of Science databases were searched, all with the time limit from database establishment to July 2022. The published randomized controlled trials of moluodan for CAG were conducted for meta-analysis and trial sequential analysis.

Results:
7 studies with a total sample size of 1143 cases were included. Compared to folic acid/vitamins, moluodan alone significantly increased the effective rate of pathological detection (relative risk [RR] = 1.73, 95% confidence interval [95%CI] = [1.48,2.02], P < .00001), and moluodan in combination with folic acid/vitamins significantly increased the effective rates of pathological detection (RR = 1.37, 95%CI = [1.23,1.52], P < .00001), gastroscopy (RR = 1.37, 95%CI = [1.18,1.60], P < .0001) and symptoms (RR = 1.25, 95%CI = [1.13,1.38], P < .0001). Harbord regression showed no publication bias (P = .22). Quality of evidence evaluation demonstrated moderate quality of evidence for all indicators.

Conclusions:
Moluodan can improve the effective rates of pathological examination, gastroscopy and symptoms in patients with CAG, and play a role in slowing down the disease progression and reducing clinical symptoms. It may be a potential drug for the treatment of CAG and has the value of further exploration.
The risks of hematological toxicities of nivolumab in cancer patients: A PRISMA-compliant meta-analysis
Authors: Shi Zuolin , Liu Xiyu , Chen Mengjia , Zhang Na , Guan Hongna , Ye Dongyang 
Published: December 2022

Background:
Nivolumab is the human programmed cell death-1 (PD-1)-blocking antibody showing significant effect in many refractory cancers. However, little is known about its risks of hematological toxicities, rare but clinically serious and potentially life-threatening adverse events. We want to explore whether nivolumab can increase the risks of hematological toxicities compared with other immunotherapy or chemotherapy drugs.

Method:
The databases of PubMed, Embase, Web of science, and CNKI were searched. We used the medical subject heading terms “Nivolumab” plus keyword “Nivolumab” to search studies published from August 1990 to October 2021. For the included articles, we calculated the relative risks and the corresponding 95% confidence intervals (CIs) for the risks of anemia, neutropenia, and leukopenia in patients treated with nivolumab versus control drugs.

Results:
Five original articles on the nivolumab trials were identified with 2399 patients enrolled in this meta-analysis. The relative risks of anemia, neutropenia, and leukopenia were 0.343 (95% CI: 0.177–0.663; P = .001), 0.020 (95% CI: 0.008–0.053; P = .000), and 0.054 (95% CI: 0.015–0.191; P = .000), respectively.

Conclusion:
The PD-1 inhibitor-nivolumab did not increase the risk of anemia, neutropenia and leukopenia. It may enhance awareness about lower risks of hematological toxicities when choosing nivolumab as PD-1 inhibitor among clinicians.
Brain natriuretic peptide as a biomarker for predicting contrast-induced nephropathy in patients undergoing coronary angiography/intervention: A systematic review and meta-analysis
Authors: Wu Xuefeng , Yang Xili , Xu Zhaoyan , Li Jianming 
Published: December 2022

Background:
Contrast-induced nephropathy (CIN) is associated with adverse events. As there are no effective treatments, the early identification of high-risk patients is required. Individual studies have suggested the utility of brain natriuretic peptide in predicting CIN. Therefore, this meta-analysis aimed to systematically investigate the value of brain natriuretic peptide in predicting CIN in patients undergoing coronary angiography (CAG) or percutaneous coronary intervention (PCI).

Methods:
We searched PubMed, Embase, Cochrane Central Register of Controlled Trials Library, and Web of Science from inception date to March 9, 2022. Studies that evaluated the predictive value of brain natriuretic peptide for CIN outcomes in patients after CAG or PCI were included. The quality of the included studies was assessed using the QUADAS-2 tool. Diagnostic accuracy estimates were calculated using a random-effects model. Subgroup and meta-regression analyses were performed to identify the potential sources of heterogeneity.

Results:
Twelve studies with 7789 patients were included in the meta-analysis. The pooled sensitivity and specificity of brain natriuretic peptide for the prediction of CIN were 0.73 (95% CI: 0.67–0.78) and 0.77 (95% CI: 0.71–0.82), respectively. The area under the summary receiver operating characteristic curve was 0.80 (95% CI: 0.77–0.84). Meta-regression analysis indicated that the sources of sensitivity heterogeneity may be the country, mean age, and study population. Additionally, country, study population, study design, and index text contributed to the specificity heterogeneity.

Conclusion:
This study demonstrated that brain natriuretic peptide could function as a novel potential marker for the early detection of CIN in patients undergoing CAG or PCI.
LncRNA LOXL1-AS1 expression in cancer prognosis: A meta-analysis
Authors: Wang Xuhua , Chen Zhaoyuan , Zhou Huaqiang , Liu Wuyang , Luo Jiaquan 
Published: December 2022

Background:
Several studies showed that LncRNA LOXL1 antisense RNA 1 (LOXL1-AS1) is overexpressed in a variety of cancers and plays a role as an oncogene in cancer. The present meta-analysis aims to elucidate the relationship between LOXL1-AS1 expression and prognosis and clinicopathological features among cancer patients.

Methods:
PubMed, Web of Science, Cochrane Library, and EMBASE database were comprehensively and systematically searched. Pooled odds ratios (ORs) and hazard ratios with a 95% confidence interval (CI) were employed to assess the relationship between LOXL1-AS1 expression and clinical outcomes and clinicopathological features in cancer patients.

Results:
The present study finally enrolled 8 studies which included 657 cancer patients. The combined results indicated that the overexpression of LOXL1-AS1 was significantly associated with shorter overall survival (pooled hazard ratio = 1.99, 95% CI 1.49–2.65, P < .00001). Meanwhile, regarding clinicopathology of cancer patients, the upregulation of LOXL1-AS1 expression was closely related to lymph node metastasis (yes vs no OR = 4.01, 95% CI: 2.02–7.96, P < .0001) and distant metastasis (yes vs no OR = 3.04, 95% CI: 1.82–5.06, P < .0001), respectively.

Conclusion:
High expression of LOXL1-AS1 in some cancers predicts shorter overall survival, distant metastasis, and lymph node metastasis. LOXL1-AS1 shows great promise as a prognostic biomarker in cancer patients.
Tislelizumab combined with anlotinib in the second-line treatment of malignant pleural mesothelioma
Authors: Zhang Dandan , Liang Jianping , Lv Yanhua , Huang Xikun , Guo Weihong 
Published: December 2022

Rationale:
Malignant pleural mesothelioma (MPM) is a malevolent tumor originated from pleura and often leads to poor prognosis. Chemotherapy of pemetrexed and cisplatin combined with antiangiogenic therapy of bevacizumab is recommended as the first-line regimen by guidelines. However, there are few sustainable second-line anti-tumor theraies that bring distinct survival benefit after the occurrence of drug resistance as the reported mPFS (median progression-free survival) scarcely exceeds 6 months. Immune checkpoint inhibitors are extensively investigated in pan-cancer, and dual immunotherapy has been listed in the first-line recommendation of MPM in several guidelines, while MPM patients benefit modestly from immune checkpoint inhibitors combination or monotherapy in second-line practice.

Patient concerns and diagnosis:
We report a 59-year-old male patient who was diagnosed with unresectable MPM in April 2021.

Interventions:
He received firstly pemetrexed combined with platinum and bevacizumab, which barely curbed disease progression; When the first line treatment failed, he was switched to tislelizumab combined with anlotinib.

Outcomes:
Tislelizumab combined with anlotinib significantly relieved his clinical symptoms, and imaging examination further validated the improvement. Until present, the second-line treatment PFS is more than 10 months.

Lessons:
The case firstly demonstrated the efficacy of tislelizumab combined with anlotinib in the second-line management of MPM. Thus, immunotherapy combined with small-molecule multi-target anti-angiogenic medication may be alternative for the second-line schemes of MPM.
Efficacy and safety of radiofrequency ablation and surgery for hepatocellular carcinoma in patients with cirrhosis: A meta-analysis
Authors: Zhang Tong , Hu He , Jia Yushan , Gao Yang , Hao Fene , Wu Jing , Yang Zhenxing , Ren Jialiang , Li Zhihao , Liu Aishi , Wu Hui 
Published: December 2022

Background:
The aim of this study was to compare the efficacy and safety of surgical resection (RES) and radiofrequency ablation (RFA) in hepatocellular carcinoma (HCC) patients with cirrhosis and to evaluate short- and long-term clinical outcomes.

Methods:
The EMBASE, Cochrane Central Register of Control Trials and Medline databases were searched for comparative studies of RES and RFA in HCC patients with cirrhosis from inception until 30 April 2021. Overall survival (OS), disease-free survival (DFS), local recurrence rate, complication rate, hospitalization duration and operation time were compared between the 2 groups. Begg’s funnel plot and Egger’s test were performed to assess publication bias.

Results:
A total of 16 studies met our inclusion criteria, including 1 randomized controlled trial. A total of 3760 patients were included, of which 2007 received RES and 1753 received RFA. The results showed that the 3-year OS rate, 5-year OS rate, 1-year DFS rate and 3-year DFS rate in the RFA group compared with the RES treatment group were significantly lower, and the local recurrence rate in the RFA group was significantly higher than that in the RES group. Compared with the RES group, the RFA group had lower postoperative complication rates, shorter operative times, and no significant difference in hospitalization duration. Subgroup analysis of laparoscopic RFA showed that there was no significant difference in 1- and 5-year OS rates and 3-year and 5-year DFS rates between the 2 groups, while the 3-year OS rates and 1-year DFS rates in the RES group were better than those in the laparoscopic RFA group.

Conclusion:
Surgery is widely applied among HCC patients with cirrhosis, providing acceptable short- and long-term results.