bluuebunny/crossref_metadata_2025_split huggingface dataset:
Simplified Pediatric Index of Mortality 3 Score by Explainable Machine Learning Algorithm
Authors: Baloglu Orkun , Nagy Matthew , Ezetendu Chidiebere , Latifi Samir Q. , Nazha Aziz 
Published: October 2021

OBJECTIVES:
Pediatric Index of Mortality 3 is a validated tool including 11 variables for the assessment of mortality risk in PICU patients. With the recent advances in explainable machine learning algorithms, we aimed to assess feasibility of application of these machine learning models to simplify the Pediatric Index of Mortality 3 scoring system in order to decrease time and labor required for data collection and entry for Pediatric Index of Mortality 3.

DESIGN:
Single-center, retrospective cohort study. Data from the Virtual Pediatric Systems for patients admitted to Cleveland Clinic Children`s PICU between January 2008 and December 2019 was obtained. Light Gradient Boosting Machine Regressor (a gradient boosting decision tree algorithm) was used for building the machine learning models. Variable importance was analyzed by SHapley Additive exPlanations. All of the 11 Pediatric Index of Mortality 3 variables were used as input variables in the machine learning models to predict Pediatric Index of Mortality 3 risk of mortality as the outcome variable. Mean absolute error, root mean squared error, and R-squared were calculated for each of the 11 machine learning models as model performance parameters.

SETTING:
Quaternary children’s hospital.

PATIENTS:
PICU patients.

INTERVENTIONS:
None.

MEASUREMENTS AND MAIN RESULTS:
Five-thousand sixty-eight patients were analyzed. The machine learning models were able to maintain similar predictive error until the number of input variables decreased to four. The machine learning model with five input variables (mechanical ventilation in the first hour of PICU admission, very-high-risk diagnosis, surgical recovery from a noncardiac procedure, low-risk diagnosis, and base excess) produced lowest mean root mean squared error of 1.49 (95% CI, 1.05–1.93) and highest R-squared of 0.73 (95% CI, 0.6–0.86) with mean absolute error of 0.43 (95% CI, 0.35–0.5) among all the 11 machine learning models.

CONCLUSIONS:
Explainable machine learning methods were feasible in simplifying the Pediatric Index of Mortality 3 scoring system with similar risk of mortality predictions compared to the original Pediatric Index of Mortality 3 model tested in a single-center dataset.
Use of Antifibrinolytics in Pediatric Life-Threatening Hemorrhage: A Prospective Observational Multicenter Study
Authors: Spinella Philip C. , Leonard Julie C. , Gaines Barbara A. , Luther James F. , Wisniewski Stephen R. , Josephson Cassandra D. , Leeper Christine M. ,   for the MAssive Transfusion epidemiology and outcomes In Children (MATIC) Investigators and BloodNet
Published: October 2021

OBJECTIVES:
To assess the impact of antifibrinolytics in children with life-threatening hemorrhage.

DESIGN:
Secondary analysis of the MAssive Transfusion epidemiology and outcomes In Children study dataset, a prospective observational study of children with life-threatening bleeding events.

SETTING:
Twenty-four children’s hospitals in the United States, Canada, and Italy.

PATIENTS:
Children 0–17 years old who received greater than 40 mL/kg of total blood products over 6 hours or were transfused under activation of massive transfusion protocol.

Intervention/Exposure:
Children were compared according to receipt of antifibrinolytic medication (tranexamic acid or aminocaproic acid) during the bleeding event.

MEASUREMENTS AND MAIN RESULTS:
Patient characteristics, medications administered, and clinical outcomes were analyzed using Cox proportional hazard and Kaplan-Meier survival analysis. The primary outcome was 24-hour mortality. Of 449 patients analyzed, median age was 7 years (2–15 yr), and 55% were male. The etiology of bleeding was 46% traumatic, 34% operative, and 20% medical. Twelve percent received antifibrinolytic medication during the bleeding event (n = 54 unique subjects; n = 18 epsilon aminocaproic acid, n = 35 tranexamic acid, and n = 1 both). The antifibrinolytic group was comparable with the nonantifibrinolytic group on baseline demographic and physiologic parameters; the antifibrinolytic group had longer massive transfusion protocol duration, received greater volume blood products, and received factor VII more frequently. In the antifibrinolytic group, there was significantly less 6-hour mortality overall (6% vs 17%; p = 0.04) and less 6-hour mortality due to hemorrhage (4% vs 14%; p = 0.04). After adjusting for age, bleeding etiology, Pediatric Risk of Mortality score, and plasma deficit, the antifibrinolytic group had decreased mortality at 6- and 24-hour postbleed (adjusted odds ratio, 0.29 [95% CI, 0.09–0.93]; p = 0.04 and adjusted odds ratio, 0.45 [95% CI, 0.21–0.98]; p = 0.04, respectively).

CONCLUSIONS:
Administration of antifibrinolytic medications during the life-threatening event was independently associated with improved 6- and 24-hour survivals in bleeding children. Consideration should be given to use of antifibrinolytics in pediatric patients with life-threatening hemorrhage.
Resistance mechanisms to osimertinib and emerging therapeutic strategies in nonsmall cell lung cancer
Authors: Zeng Yue , Yu Danlei , Tian Wentao , Wu Fang 
Published: October 2021

Purpose of review
This review aims to introduce the resistance mechanisms to osimertinib, discuss the therapeutic strategies, and make clinical updates in overcoming resistance to osimertinib.

Recent findings
Osimertinib has shown favorable efficacy on second-line and first-line treatments in EGFR-mutant advanced nonsmall cell lung cancer (NSCLC). However, the presence of primary and acquired resistance to osimertinib restricts its clinical benefits. The primary resistance mainly consists of BIM deletion polymorphism and EGFR exon 20 insertions. Meanwhile, the heterogeneous mechanisms of acquired resistance include EGFR-dependent (on-target) and EGFR-independent (off-target) mechanisms. EGFR C797S mutation, MET amplification, HER2 amplification, and small cell lung cancer transformation were identified as frequent resistance mechanisms. Recently, more novel mechanisms, including rare EGFR point mutations and oncogenic fusions, were reported. With the results of completed and on-going clinical trials, the emerging therapeutic strategies of postosimertinib progression are summarized.

Summary
The resistance mechanisms to osimertinib are heterogeneous and gradually perfected. The combination of osimertinib with bypass targeted therapy and other therapeutic approaches emerge as promising strategies.
Mild Renal Dysfunction and Risk of Thromboembolism and Bleeding in Patients with Atrial Fibrillation: The Chinese Atrial Fibrillation Registry Study
Authors: Li Jingye , Li Sitong , Jiang Chao , Du Jing , Guo Xueyuan , Li Songnan , Jiang Chenxi , Tang Ribo , Sang Caihua , Long Deyong , Du Xin , Dong Jianzeng , Ma Changsheng 
Published: October 2021

Abstract

Objective:
Previous studies indicated that patients with atrial fibrillation (AF) and moderate-to-severe chronic kidney disease (CKD) are at a higher risk of thromboembolism and bleeding during anticoagulation. Whether mild CKD is associated with an increased risk of thromboembolism and bleeding in AF patients remains unknown. This study aimed to evaluate the impact of mild CKD on thromboembolism and major bleeding among patients with AF.

Methods:
Baseline serum creatinine was available in 17,559 of 25,512 patients enrolled in the China-AF study between August 2011 and December 2018. After excluding those who underwent AF ablation or with moderate-to-severe CKD, 7191 non-valvular AF patients (2059 with mild CKD and 5132 with normal renal function) with regular follow-up for at least 6 months were included. Primary outcomes were the time to the first occurrence of thromboembolic and major bleeding events.

Results:
Over a mean follow-up of (44.4 ± 23.4) months, 639 thromboembolism and 231 major bleeding events occurred. The crude incidence rates of thromboembolism were higher in the mild CKD group than that of the normal renal function group (3.0/100 person-years vs. 2.2/100 person-years, P < 0.0001), while the crude incidence rates of major bleeding were comparable between the two groups (1.0/100 person-years vs. 0.8/100 person-years, P = 0.076). After multivariate analyses, mild CKD was not associated with an increased risk of thromboembolism (HR = 1.05, 95% CI: 0.89–1.25, P = 0.547) or major bleeding (HR = 1.11, 95% CI: 0.84–1.47, P = 0.476).

Conclusions:
Mild CKD was not an independent risk factor of thromboembolism or major bleeding in patients with AF.
Antiviral Abidol is Associated with the Reduction of In-Hospital Mortality in COVID-19 Patients
Authors: Zeng Hesong , He Xingwei , Liu Wanjun , Kan Jing , He Liqun , Zhao Jinhe , Chen Cynthia , Zhang Junjie , Chen Shaoliang 
Published: October 2021

Abstract

Objective:
Coronavirus disease 2019 (COVID-19) is a global public health crisis. There are no specific antiviral agents for the treatment of SARS-CoV-2. Information regarding the effect of Abidol on in-hospital mortality is scarce. The present study aimed to evaluate the treatment effect of Abidol for patients with COVID-19 before and after propensity score matching (PSM).

Methods:
This retrospective cohort study analyzed 1019 patients with confirmed COVID-19 in China from December 22, 2019 to March 13, 2020. Patients were divided to Abidol (200 mg, tid, 5–7 days, n = 788, 77.3%) and No-Abidol (n = 231, 22.7%) groups. The primary outcome was the mortality during hospitalization.

Results:
Among 1019 COVID-19 patients, the age was (60.4 ± 14.5) years. Abidol-treated patients, compared with No-Abidol-treated patients, had a shorter duration from onset of symptoms to admission, less frequent renal dysfunction, lower white blood cell counts (lymphocytes <0.8) and erythrocyte sending rate, lower interleukin-6, higher platelet counts and plasma IgG and oxygen saturation, and less frequent myocardial injury. The mortality during hospitalization before PSM was 17.9% in Abidol group and 34.6% in No-Abidol (hazard ratio (HR) = 2.610, 95% confident interval (CI): 1.980–3.440), all seen in severe and critical patients. After PSM, the in-hospital death was 13.6% in Abidol and 28.6% in No-Abidol group (HR = 2.728, 95% CI: 1.598–4.659).

Conclusions:
Abidol-treatment results in less in-hospital death for severe and critical patients with COVID-19. Further randomized study is warranted to confirm the findings from this study.
Upregulation of Cartilage Oligomeric Matrix Protein and Bone Morphogenetic Protein-2 May Associate with Calcific Aortic Valve Disease
Authors: Xu Yueyue , Cao Yide , Liu Yafeng , Wang Jingsong , Chen Ganyi , Tao Zhonghao , Yao Yiwei , Cai Yuchen , Wu Yunzhang , Chen Wen 
Published: October 2021

Abstract

Objective:
Calcific aortic valve disease (CAVD) affects millions of elderly people, and there is currently no effective way to stop or slow down its progression. Therefore, exploring the pathogenesis of CAVD is very important for prevention and treatment. Cartilage oligomeric matrix protein (COMP) have important role in cell phenotype change. This study is aimed to confirm whether COMP participate in CAVD and try to find the possible mechanisms.

Methods:
Human aortic valve tissues from Nanjing First Hospital (CAVD group, n = 20; control group, n = 11) were harvested. The expression level of COMP was tested by western blot and immunohistochemistry. Dual immunofluorescence staining was used for locating COMP. Bone morphogenetic protein-2 (BMP2) signalling were tested by western blot. The animal model was also used to detect COMP level by immunohistochemistry.

Results:
The results showed that the expression level of COMP was significantly increased in the calcific valve samples when compared with that of the control valve (P < 0.05); COMP was expressed near the calcific nodules and co-localized with α-smooth muscle actin (α-SMA). The protein levels of BMP2 and p-Smads 1/5/9 were markedly more highly expressed in the CAVD group than the control group (P < 0.05). Furthermore, immunofluorescence detection showed that COMP and BMP2 were co-located in calcific valves.

Conclusions:
The above results suggested that upregulation of COMP and BMP2 may be associated with aortic valve calcification and that COMP may become a potential therapeutic target in human CAVD.
Bivalirudin in Primary PCI: Can Its Glory Being Restored?
Authors: Li Yang , Li Yi , Stone Gregg W. , Han Yaling 
Published: October 2021

Abstract
Intravenous anticoagulant therapy is critical to prevent ischemic recurrences and complications without increasing the risk of bleeding in patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PPCI). It includes the indirect thrombin inhibitor heparins and the direct thrombin inhibitor bivalirudin. However, the ideal anticoagulant for patients undergoing PPCI remains controversial. In this review, we provide an overview of currently available anticoagulant therapies used in STEMI patients undergoing PPCI, including describing the rationale for their use, pivotal clinical trial data, and treatment recommendations of guidelines, providing much-needed clarity to guide the selection of the safest and most effective anticoagulant regimens for PPCI.
Surgical Treatment of Left Atrial Dissection and Severe Mitral Valve Obstruction
Authors: Chen Antian , Ma Guotao , Yang Deyan , Wang Chenyu , Liu Yingxian 
Published: October 2021

Abstract
Left atrial dissection is a rare complication of mitral valve replacement surgery. Here, a case of left atrial dissection followed by mitral valvular obstruction was presented. It is suspected that the dissection was caused by trematodiases infection. Cardiac surgery was finally performed, which not only confirmed the diagnosis but also acted as an effective treatment. Especially, surgery is of essential value to confirm the perforation locating at the basal posterior wall of the left ventricle, to repair the atrial dissection, and to relieve the mitral valvular obstruction.
Rationale and Design of a Randomized Controlled Trial on Intensive Management of Blood PRESSure and Cholesterol in Elderly Chinese with Hypertension and Atrial FibrillatION (IMPRESSION)
Authors: Zhang Wei , Chen Yi , Huang Qifang , Wang Ji-Guang 
Published: October 2021

Abstract
Hypertension significantly increases the risk of embolic stroke and systemic embolism in patients with atrial fibrillation, while statin therapy can improve long-term outcomes in hypertensive patients at high risk. However, it is still unclear whether patients with both hypertension and atrial fibrillation can benefit from intensive management of blood pressure and cholesterol. IMPRESSION is a 3-year prospective, randomized, open-label, blinded-endpoint investigation. A total of 1200 hypertensive patients with atrial fibrillation from about 40 clinical centers nationwide will be included upon confirming the presence of both hypertension and atrial fibrillation and will be randomly assigned to groups for intensive or standard management of blood pressure and cholesterol. Patients in all groups will have office and home blood pressure measured by the end of the first month and every 3 months thereafter. The effects of blood pressure and cholesterol management strategies in patients with hypertension and atrial fibrillation on fatal and non-fatal stroke, acute myocardial infarction, and cardiovascular death at 3 years will be assessed. The IMPRESSION study protocol has received approval from the Ethics Committee of Ruijin Hospital, Shanghai Jiaotong University School of Medicine. The procedures set out in this protocol are in accordance with the principles of the Declaration of Helsinki and Good Clinical Practice guidelines. The results will be published following the CONSORT statement in a peer-reviewed scientific journal (Trial registration number: NCT04111419).
Upregulation of miR-345-5p suppresses cell growth of lung adenocarcinoma by regulating ras homolog family member A (RhoA) and Rho/Rho associated protein kinase (Rho/ROCK) pathway
Authors: Zhou Qiao-Yun , Gui Shu-Yu , Zhang Peng , Wang Mei 
Published: October 2021

Abstract

Background:
Microribose nucleic acids (miRNAs) are implicated in the progression of lung adenocarcinoma. MicroRNA-345-5p (miR-345-5p) is a recently identified anti-oncogene in some human cancers, but its functional role and possible molecular mechanism in lung adenocarcinoma remain unknown. This study aimed to identify the biological function and underlying mechanism of miR-345-5p in lung adenocarcinoma cells.

Methods:
In this study, lung adenocarcinoma tissues and adjacent tissues were collected in the First Affiliated Hospital of Anhui Medical University between April 2016 and February 2017. The expression of miR-345-5p and ras homolog family member A (RhoA) in lung adenocarcinoma tissues and human lung adenocarcinoma cell lines (A549, H1650, PC-9, and H441) was detected by reverse transcription quantitative polymerase chain reaction analysis. Functional assays including colony formation, flow cytometry analysis, wound healing, and transwell assays were performed to assess the proliferation, apoptosis, migration, and invasion of lung adenocarcinoma cells. In addition, RNA pulldown and luciferase reporter assays were conducted to evaluate the relationship between miR-345-5p and RhoA. Difference between the two groups was analyzed with Student's t test, while that among multiple groups was analyzed with one-way analysis of variance.

Results:
MiR-345-5p expression displayed lower level in lung adenocarcinoma tissues (0.241 ± 0.095 vs.1.000 ± 0.233, t = 19.247, P < 0.001) and cell lines (F = 56.992, P < 0.001) than control tissues and cells. Functional experiments demonstrated that upregulation of miR-345-5p inhibited the malignant phenotypes of lung adenocarcinoma cells via suppressing cell proliferation, migration, invasion, and facilitating cell apoptosis. Additionally, RhoA was verified to be the downstream target of miR-345-5p. Expression of RhoA was downregulated by overexpression of miR-345-5p in PC-9 (0.321 ± 0.047 vs. 1.000 ± 0.127, t = 8.536, P < 0.001) and H1650 (0.398 ± 0.054 vs. 1.000 ± 0.156, t = 4.429, P = 0.011) cells. Rescue assays revealed that overexpression of RhoA rescued the suppressive effects of miR-345-5p upregulation on proliferation, migration, and invasion of lung adenocarcinoma cells. Further, miR-345-5p was found to regulate the Rho/Rho-associated protein kinase (ROCK) signaling pathway by downregulation of RhoA in lung adenocarcinoma cells.

Conclusions:
MiR-345-5p plays a tumor suppressor role in lung adenocarcinoma cells by downregulating RhoA to inactivate the Rho/ROCK pathway.
Risk factors associated with osteoporosis and fracture in psoriatic arthritis
Authors: Wang Yu , Song Zhi-Bo , Deng Xue-Rong , Zhang Xiao-Hui , Zhang Zhuo-Li 
Published: October 2021

Abstract

Background:
Although there are few studies mentioned there may be some relationship between psoriatic arthritis (PsA) and osteoporosis, clinical data in real world still need to be clarified in China. The aim of this study was to assess the areal and volumetric bone mineral density (BMD), frequency of fracture, and risk factors in patients with PsA.

Methods:
A total of one hundred PsA patients who visited Peking University First Hospital and one hundred age- and sex-matched healthy controls with DXA data were enrolled in the study. Patients with clinical fractures confirmed by X-ray during follow-up were also recorded. Clinical characteristics of the patients were recorded and compared between the abnormal BMD group and the normal BMD group, as well as between the fracture and non-fracture groups. Risk factors for fracture and low BMD were analyzed.

Results:
Mean BMD at the total hip and femoral neck was significantly lower in PsA patients than that in healthy controls (0.809 ± 0.193 vs. 0.901 ± 0.152 g/cm2, P
= 0.041; 0.780 ± 0.146 vs. 0.865 ± 0.166 g/cm2, P
= 0.037, respectively). Moreover, lumbar spine BMD was negatively correlated with psoriasis duration, swollen joint count and DAS28-CRP (r = –0.503, –0.580, –0.438; P < 0.05). Total hip BMD and femoral neck BMD were negatively correlated with HAQ (r = –0.521, –0.335; P < 0.05). Fractures occurred in 29 patients during the follow-up period. Logistic regression analysis showed that older age (OR 1.132 [95%CI: 1.026–1.248), P < 0.05], higher HAQ score (OR 1.493, 95%CI: 1.214–1.836, P < 0.01), higher disease activity index for psoriatic arthritis (OR 1.033, 95% CI: 1.002–1.679, P < 0.05) and hip joint involvement (OR 6.401, 95% CI: 4.012–44.180, P < 0.05) were risk factors for fracture in the multivariate model.

Conclusions:
Increased risks of osteoporosis and fracture were found in PsA patients compared to healthy controls. Besides age, high disease activity and hip joint involvement were risk factors for decreased BMD and fracture.
Role of Pericytes in Diabetic Angiogenesis
Authors: Wang Tianyou , Zang Guangyao , Zhang Lili , Sun Zhen , Liu Jia , Hou Lina , Wang Zhongqun 
Published: October 2021

Abstract:
In the context of diabetes mellitus, various pathological changes cause tissue ischemia and hypoxia, which can lead to the compensatory formation of neovascularization. However, disorders of the internal environment and dysfunctions of various cells contribute to the dysfunction of neovascularization. Although the problems of tissue ischemia and hypoxia have been partially solved, neovascularization also causes many negative effects. In the process of small blood vessel renewal, pericytes are extremely important for maintaining the normal growth and maturation of neovascularization. Previously, our understanding of pericytes was very limited, and the function of pericytes was not yet clear. Recently, multiple new functions of pericytes have been identified, affecting various processes in angiogenesis and relating to various diseases. Therefore, the importance of pericytes has gradually become apparent. This article presents the latest research progress on the role of pericytes in diabetic angiogenesis, characterizes pericytes, summarizes various potential therapeutic targets, and highlights research directions for the future treatment of various diabetes-related diseases.
Catalpol Alleviates Ang II-Induced Renal Injury Through NF‐κB Pathway and TGF-β1/Smads Pathway
Authors: Cong Cong , Yuan Xiaohong , Hu Ying , Chen Wenjing , Wang Yong , Tao Lei 
Published: October 2021

Abstract:
Catalpol is an iridoid glycoside obtained from Rehmannia glutinosa, which in previous studies showed various pharmacological properties, including anti-inflammatory, antioxidant, antidiabetic, antitumor, and dopaminergic neurons protecting effects. Here, we examined the effect of catalpol on renal injury induced by angiotensin II (Ang II) and further to explore its latent molecular mechanisms. We used an in vivo model of Ang II-induced renal injury mice; catalpol (25, 50, and 100 mg/kg) was administered for 28 days. Mouse glomerular mesangial cells (SV40 MES 13), rat kidney interstitial fibroblasts cells (NRK-49F), and human proximal tubular epithelial cells (HK-2) were induced by Ang II (10 µM) in the presence or absence of catalpol (1, 5, and 10 µM) and incubated for 48 hours in vitro. In our study, periodic acid-Schiff and Masson staining of renal tissue showed that catalpol reduced Ang II-induced renal injury in a concentration-dependent manner. The positive expressions of collagen IV and TGF-β1 were observed to decrease sharply after catalpol treatment. In renal tissue, the levels of pro-inflammatory cytokines tumor necrosis factor α and interleukin 6 were evidently decreased after catalpol intervention. Catalpol can relieve Ang II-induced renal injury by inactivating NF‐κB and TGF-β1/Smads signaling pathways. Therefore, catalpol may act as a potential drug to treat Ang II-induced renal injury.