bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effectiveness and mechanism of metformin in animal models of pulmonary fibrosis: A preclinical systematic review and meta-analysis
Authors: Wu Xuanyu , Xiao Xiang , Chen Xinyu , Yang Maoyi , Hu Zhipeng , Shuai Sijia , Fu Qinwei , Yang Han , Du Quanyu 
Published: September 2022

Background: Pulmonary fibrosis (PF) is a lung disease with no curative drug, characterized by a progressive decrease in lung function. Metformin (MET) is a hypoglycemic agent with the advantages of high safety and low cost and has been used in several in vivo trials to treat fibrotic diseases.Objective: This study aimed to explore the efficacy and safety of MET in treating PF and elaborate on its mechanism.Methods: Eight databases were searched for in vivo animal trials of MET for PF from the time of database creation until 1 March 2022. The risk of bias quality assessment of the included studies was conducted using SYRCLE’s risk of bias assessment. Pulmonary inflammation and fibrosis scores were the primary outcomes of this study. Hydroxyproline (HYP), type I collagen (collagen I), α-smooth muscle actin (α-SMA), transforming growth factor-β (TGF-β), Smad, AMP-activated protein kinase (AMPK), and extracellular signal–regulated kinase (ERK) protein expression in lung tissues and animal mortality were secondary outcomes. Effect magnitudes were combined and calculated using Revman 5.3 and Stata 16.0 to assess the efficacy and safety of MET in animal models of PF. Inter-study heterogeneity was examined using the I2 or Q test, and publication bias was assessed using funnel plots and Egger’s test.Results: A total of 19 studies involving 368 animals were included, with a mean risk of bias of 5.9. The meta-analysis showed that MET significantly suppressed the level of inflammation and degree of PF in the lung tissue of the PF animal model. MET also reduced the content of HYP, collagen I, α-SMA, and TGF-β and phosphorylation levels of Smad2, Smad3, p-smad2/3/smad2/3, ERK1/2, and p-ERK1/2/ERK1/2 in lung tissues. MET also elevated AMPK/p-AMPK levels in lung tissues and significantly reduced animal mortality.Conclusion: The results of this study suggest that MET has a protective effect on lung tissues in PF animal models and may be a potential therapeutic candidate for PF treatment.Systematic Review Registration:https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=327285, identifier CRD42022327285.
Literature review of the clinical characteristics of metformin-induced hepatotoxicity
Authors: Wang Chunjiang , Deng Hongyi , Xu Yunfei , Liu Ying 
Published: September 2022

Background: Knowledge of metformin-induced hepatotoxicity is based on case reports. The aim of this study was to investigate the clinical features of metformin-induced hepatotoxicity.Methods: We collected relevant literature on metformin-induced hepatotoxicity published from January 1994 to February 2022 by searching Chinese and English databases.Results: Thirty patients (19 males and 11 females) from 29 articles were included, with a median age of 61 years (range 29–83). The median time to onset of liver injury was 4 weeks (range 0.3–648) after metformin administration. Clinical symptoms occurred in 28 patients, including gastrointestinal reactions (56.7%), jaundice (50.0%), fatigue (36.7%), anorexia (23.3%), pruritus (13.3%), dark urine (13.3%), and clay-colored stools (10.0%). Serum alanine transaminase, aspartate transaminase, γ-glutamyl transferase, total bilirubin and alkaline phosphatase were elevated to varying degrees. Liver imaging in 26 patients showed hepatic steatosis (6 cases, 23.1%) and gallbladder wall thickening (11.5%). Liver biopsies from 13 patients showed portal phlebitis (61.5%), cholestatic hepatitis (38.5%), and parenchymal inflammation (38.5%). After metformin discontinuation, liver function returned to normal levels at a median of 6 weeks (range 2–16).Conclusions: Metformin-induced hepatotoxicity is a rare adverse reaction. Physicians and patients should be alert to metformin-induced hepatotoxicity.
Development of a UPLC-MS/MS method for the determination of orelabrutinib in rat plasma and its application in pharmacokinetics
Authors: Liu Ya-nan , Hu Yingying , Wang Jing , Chen Chaojie , Cai Jianping , Xu Ren-ai , Lu Zhongqiu 
Published: September 2022

The aim of the present study was to establish an ultra performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) method for the determination of orelabrutinib in rat plasma using futibatinib as internal standard (IS), and to apply it for a pharmacokinetic study in rats. Orelabrutinib was extracted from plasma by protein precipitation and quantitatively analyzed by UPLC-MS/MS. An Acquity UPLC BEH C18 column was used for rapid separation by gradient elution using 0.1% formic acid and acetonitrile as mobile phases. The validation results of bioanalytical methodology showed that the linearity of orelabrutinib in plasma samples was good within the concentration range of 1–2000 ng/ml. The lower limit of quantification (LLOQ) was 1 ng/ml. The precision of orelabrutinib ranged from 1.4% to 11.5%, with intra-day and inter-day accuracy ranging from −5.7% to 7.7% and −0.2% to 12.5%, respectively. The selectivity, stability, matrix effect and recovery of the method all met the requirements of quantitative analysis of biological samples. The method was simple, sensitive, accurate and specific, and had high recovery rate. It also could be successfully applied to the pharmacokinetic study of rats.
High speed two-photon laser scanning stereomicroscopy for three-dimension tracking multiple particles simultaneously in three-dimension
Authors: Chen Xun , Li Yang , Chen Peng , Yao Hai , Ye Tong 
Published: September 2022

In this paper, we will describe a video rate two-photon laser scanning stereomicroscopy for imaging-based three-dimensional particle tracking. Using a resonant galvanometer, we have now achieved 30 volumes per second (frame size 512 × 512) in volumetric imaging. Owing to the pulse multiplexing and demultiplexing techniques, the system does not suffer the speed loss for taking two parallax views of a volume. The switching time between left and right views is reduced to several nanoseconds. The extremely fast view switching and high volumetric imaging speed allow us to track fast transport processes of nanoparticles in deep light-scattering media. For instance, in 1%-intralipid solution and fibrillar scaffolds, the tracking penetration depth can be around 400 µm.
A comparison of muscle activation and concomitant intermuscular coupling of antagonist muscles among bench presses with different instability degrees in untrained men
Authors: Wang Lejun , Qiao Minjie , Tao Haifeng , Song Xiaoqian , Shao Qineng , Wang Ce , Yang Hua , Niu Wenxin , Chen Yiqing 
Published: September 2022

The aim of this study was to analyze and compare the muscle activation and concomitant intermuscular coupling of antagonist muscles among bench presses with different instability degrees. Twenty-nine untrained male college students performed bench press exercises at an intensity of 60% 1 RM on three conditions: small unstable bench press with Smith machine (SBP), medium unstable bench press of free weight (FWBP), and large unstable bench press with increased instability by suspending the load with elastic bands (IIBP). One-way repeated measures analysis of variance was used to compare integrated EMG activity values of the biceps brachii (BB), posterior deltoid (PD), long head of the triceps brachii (TB), anterior deltoid (AD), upper portion of the pectoralis major (PM) muscles, and phase synchronization index (PSI) of BB-TB and PD-AD antagonist muscle pairs. A higher integrated EMG of BB muscle was found during bench press with a more unstable condition. IIBP showed a higher integrated EMG of prime movers (TB, AD, and PM) and stabilizing of BB than SBP and FWBP. PSI between muscle pairs of BB-TB in the gamma frequency band was higher in SBP than the other bench presses with unstable conditions, which may be related to the optimal “internal model” for antagonist muscles during bench press exercise. Therefore, IIBP training may be an effective accessory exercise to maintain a higher level of muscle activation across primary and stabilizing muscles with a lighter load for untrained men, while SBP may be a suitable bench press exercise for untrained participants who have not developed the neuromuscular adaptations necessary for correct stabilization of the elbow joint.
The impacts of COVID-19 on eating disorders and disordered eating: A mixed studies systematic review and implications
Authors: McLean Courtney P. , Utpala Ranjani , Sharp Gemma 
Published: September 2022

PurposeThe unique constraints to everyday life brought about by the COVID-19 pandemic have been suggested to negatively impact those with pre-existing mental health issues such as eating disorders. While individuals with eating disorders or disordered eating behaviors likely represent a vulnerable group to the COVID-19 pandemic, the impact of the pandemic is yet to be fully established.MethodsWe systematically examined the impact of the COVID-19 pandemic on eating disorders and disordered eating behaviors. We searched electronic databases MEDLINE, PsycINFO, CINAHL, and EMBASE for literature published until October 2021. Eligible studies were required to report on individuals with or without a diagnosed eating disorder or disordered eating behaviors who were exposed to the COVID-19 pandemic.FindingsSeventy-two studies met eligibility criteria with the majority reporting an increase in eating disorder or disordered eating behaviors associated with the COVID-19 pandemic. Specifically, it appears children and adolescents and individuals with a diagnosed eating disorder may present vulnerable groups to the impacts of the COVID-19 pandemic.DiscussionThis mixed systematic review provides a timely insight into COVID-19 eating disorder literature and will assist in understanding possible future long-term impacts of the pandemic on eating disorder behaviors. It appears that the role of stress in the development and maintenance of eating disorders may have been intensified to cope with the uncertainty of the COVID-19 pandemic. Future research is needed among understudied and minority groups and to examine the long-term implications of the COVID-19 pandemic on eating disorders and disordered eating behaviors.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/display_record.php?RecordID=284749, PROSPERO [CRD42021284749].
The therapeutic alliance in cognitive-behavioral therapy for obsessive-compulsive disorder: A systematic review and meta-analysis
Authors: Strappini Francesca , Socci Valentina , Saliani Angelo Maria , Grossi Giuseppe , D’Ari Giulia , Damato Titti , Pompili Nicole , Alessandri Guido , Mancini Francesco 
Published: September 2022

BackgroundThe therapeutic alliance has been recognized as one of the most researched key elements of treatment across different therapeutic approaches and diagnostic domains. Despite its importance, our current understanding of its clinical relevance in patients with obsessive-compulsive disorder (OCD) is still debated. This study aimed to examine empirical evidence on the effect of alliance on treatment outcomes in Cognitive Behavioral Therapy (CBT) in patients with OCD in a systematic review and meta-analysis.MethodsOriginal peer-reviewed articles until March 2022 were included if they were (1) written in English; (2) included a clinical group with a current primary OCD diagnosis; (3) involved individual CBT; (4) used a validated therapeutic alliance scale that was related to the outcome measurement; (5) reported an effect size.ResultsThirteen studies were included, six of which contained sufficient statistical information to be included in the meta-analysis. A total of 897 patients took part in all reviewed studies. We found a modest effect of alliance on post-treatment outcome [Tau2 = −0.1562 (C.I. 95%: −0.2542 to −0.0582)].DiscussionThe results show the existence of considerable variability and methodological inconsistencies across studies. We discuss the role of methodological factors that could account for this divergence, the research limitations, and the implications for current research.Systematic review registration[https://osf.io/dxez5/?view_only=bc2deaa7f0794c8dbef440255b2d4b3b].
Magnetic resonance imaging T2* of the pancreas value using an online software tool and correlate with T2* value of myocardium and liver among patients with transfusion-dependent thalassemia major
Authors: Hoe Han Guan , Git Kim-Ann , Loh C-Khai , Abdul Latiff Zarina , Hong Joyce , Abdul Hamid Hamzaini , Wan Sulaiman Wan Noor Afzan , Mohd Zaki Faizah 
Published: September 2022

ObjectivePatients with thalassemia major do require lifetime blood transfusions that eventually result in iron accumulation in different organs. We described the usefulness of using magnetic resonance imaging (MRI) T2*imaging values for the evaluation of pancreatic iron load in these patients, and we correlated it with MRI T2* haemosiderosis of the myocardium and liver that has been recognized as a non-invasive assessment of iron overload among patients with thalassemia major.Materials and methodsWe conducted a cross-sectional study on 39 patients with thalassemia major in one of the tertiary university hospitals for a 1-year period. Demographic data were collected from the patient's history. MRI T2* of the pancreas, liver, and heart were executed on all patients in the same setting. Objective values of iron overload in these organs were obtained using the MRI post-processing software from online software.ResultsA total of 32 (82.1%) patients had pancreatic iron overload including 2 patients (5.1%) with severe iron overload and 15 patients (38.5%) with moderate and mild iron overload, respectively. Nine patients (23.1%) had myocardial iron overload, which included 3 patients (7.7%) who had severe cardiac haemosiderosis. Notably, 37 patients (94.9%) had liver iron overload, which included 15 patients (38.5%) who had severe liver haemosiderosis. There was a moderate positive correlation between the relaxation time of the pancreas and heart haemosiderosis (r = 0.504, P &lt; 0.001). No significant correlation was found between the relaxation time of the pancreas with the liver and the heart with the liver.ConclusionPancreatic haemosiderosis precedes cardiac haemosiderosis, which establishes a basis for initiating earlier iron chelation therapy to patients with thalassemia major.
Classification of expert-level therapeutic decisions for degenerative cervical myelopathy using ensemble machine learning algorithms
Authors: Park Dougho , Cho Jae Man , Yang Joong Won , Yang Donghoon , Kim Mansu , Oh Gayeoul , Kwon Heum Dai 
Published: September 2022

BackgroundTherapeutic decisions for degenerative cervical myelopathy (DCM) are complex and should consider various factors. We aimed to develop machine learning (ML) models for classifying expert-level therapeutic decisions in patients with DCM.MethodsThis retrospective cross-sectional study included patients diagnosed with DCM, and the diagnosis of DCM was confirmed clinically and radiologically. The target outcomes were defined as conservative treatment, anterior surgical approaches (ASA), and posterior surgical approaches (PSA). We performed the following classifications using ML algorithms: multiclass, one-versus-rest, and one-versus-one. Two ensemble ML algorithms were used: random forest (RF) and extreme gradient boosting (XGB). The area under the receiver operating characteristic curve (AUC-ROC) was the primary metric. We also identified the variable importance for each classification.ResultsIn total, 304 patients were included (109 conservative, 66 ASA, 125 PSA, and 4 combined surgeries). For multiclass classification, the AUC-ROC of RF and XGB models were 0.91 and 0.92, respectively. In addition, ML models showed AUC-ROC values of &gt;0.9 for all types of binary classifications. Variable importance analysis revealed that the modified Japanese Orthopaedic Association score and central motor conduction time were the two most important variables for distinguishing between conservative and surgical treatments. When classifying ASA and PSA, the number of involved levels, age, and body mass index were important contributing factors.ConclusionML-based classification of DCM therapeutic options is valid and feasible. This study can be a basis for establishing generalizable ML-based surgical decision models for DCM. Further studies are needed with a large multicenter database.
Case Fatality Rate of COVID-19 and its Relationship to Sociodemographic Characteristics in Ecuador, 2020
Authors: Flores Sacoto Karla Margarita , Sanchez Del Hierro Galo Antonio , Moreno-Piedrahita Hernández Felipe Gonzalo , Jarrin Estupiñan Jose Xavier 
Published: September 2022

Objective: To analyze sociodemographic factors’ influence on COVID-19 case fatality rate (CFR) in Ecuador on a subnational level.Methods: Publicly available register-based observational study. A retrospective cohort of COVID-19 infections between epidemiological weeks 8–53 in the Ecuadorian public healthcare system was determined from available records. Statistical analyses were conducted to evaluate CFR trends according to factors such as sex, age, location, and healthcare provider.Results: Overall CFR was 9.4%; by canton, median CFR was 5.2%, with some cantons with much higher rates, like Santa Elena (39.1%). Overall CFR decreased during the period, from 16.6% (week 8) to 2.63% (week 53). Being in a rural area was an independent protective factor. Patients over 65 had a hazard ratio of 11.38 (95% CI [11.05, 11.72]). Sex, ethnicity, and treatment from public facilities were also associated with death risk.Conclusion: CFR is a proxy indicator of COVID-19 impact in Ecuador, and this location-based analysis provides new information on the disease’s specific impact subnationally. Overall COVID-19 CFR during the entire period was high, suggesting the need to improve COVID-19 care in Ecuador.
The Pathologic Complete Response Ratio of Liver Metastases Represents a Valuable Prognostic Indicator
Authors: Xu Yanbo , He Jiarui , Li Weihao , Zhang Weili , Liu Songran , He Jiahua , Pan Zhizhong , Lu Zhenhai , Peng Jianhong , Lin Junzhong 
Published: September 2022

Background and Objectives: The aim of this study was to evaluate the role of the pathologic complete response ratio of liver metastases (PCRRLM) in predicting the prognosis and recurrence of colorectal cancer liver metastases (CRLM).Methods: A total of 305 CRLM patients who underwent preoperative chemotherapy followed by hepatectomy were included. PCRRLM was defined as the number of liver metastases exhibiting pathologic complete response (PCR) divided by the number of total resected liver metastases. The Kaplan–Meier method was used to calculate survival, and differences were examined by the log-rank test. Univariate and multivariate analyses were performed to identify the predictors of PCRRLM, recurrence-free survival (RFS) and overall survival (OS).Results: Among the 305 included patients, 44 (14.4%) achieved a PCRRLM ≥0.50 (including PCRRLM = 1), and 261 (85.6%) achieved a PCRRLM &lt;0.50 (including PCRRLM = 0). Patients of an older age (≥55 years old) and those with higher carcinoembryonic antigen (CEA) levels (≥5 ng/ml) were less likely to achieve a PCRRLM ≥0.50. In the multivariate analysis, PCRRLM≥ 0.50 (vs. &lt; 0.50, HR [95% CI]: 0.67 [0.46–0.99], p = 0.043) was associated with better RFS. Positive lymph node status (vs. negative, HR [95% CI]: 1.46 [1.04–2.05], p = 0.028) and TBS ≥5 (vs. &lt; 5, HR [95% CI]: 1.44 [1.02–2.04], p = 0.038) were associated with worse RFS.Conclusion: PCRRLM was significantly associated with long-term RFS after preoperative chemotherapy and CRLM resection. Thus, it may be a valuable indicator of recurrence in CRLM patients.
An Optimized Solution for Fault Detection and Location in Underground Cables Based on Traveling Waves
Authors: Tariq Rizwan , Alhamrouni Ibrahim , Rehman Ateeq Ur , Tag Eldin Elsayed , Shafiq Muhammad , Ghamry Nivin A. , Hamam Habib 
Published: September 2022

Faults in the power system affect the reliability, safety, and stability. Power-distribution systems are familiar with the different faults that can damage the overall performance of the entire system, from which they need to be effectively cleared. Underground power systems are more complex and require extra accuracy in fault detection and location for optimum fault management. Slow processing and the unavailability of a protection zone for relay coordination are concerns in fault detection and location, as these reduce the performance of power-protection systems. In this regard, this article proposes an optimized solution for a fault detection and location framework for underground cables based on a discrete wavelet transform (DWT). The proposed model supports area detection, the identification of faulty sections, and fault location. To overcome the abovementioned facts, we optimize the relay coordination for the overcurrent and timing relays. The proposed protection zone has two sequential stages for the current and time at which it optimizes the current and time settings of the connected relays through Newton–Raphson analysis (NRA). Moreover, the traveling times for the DWT are modeled, which relate to the protection zone provided by the relay coordination, and the faulty line that is identified as the relay protection is not overlapped. The model was tested for 132 kV/11 kV and 16-node networks for underground cables, and the obtained results show that the proposed model can detect and locate the cable’s faults speedily, as it detects the fault in 0.01 s, and at the accurate location. MATLAB/Simulink (DigSILENT Toolbox) is used to establish the underground network for fault location and detection.
Genome-Wide Identification and Expression Analysis of the NAC Gene Family in Alfalfa Revealed Its Potential Roles in Response to Multiple Abiotic Stresses
Authors: He Fei , Zhang Lixia , Zhao Guoqing , Kang Junmei , Long Ruicai , Li Mingna , Yang Qingchuan , Chen Lin 
Published: September 2022

NAC (NAM, ATAF1/2, and CUC2) transcription factors compose one of the largest families of plant-specific transcription factors; they are widely involved in plant growth and development and have especially important roles in improving stress resistance in plants. However, NAC gene family members in alfalfa (Medicago sativa L.) have not been systematically identified and analyzed genome-wide due to the complexity of the alfalfa reference genome. In this study, a total of 421 M. sativa NAC genes (MsNACs) were identified from the alfalfa “Xinjiangdaye” reference genome. Basic bioinformatics analysis, including characterization of sequence length, protein molecular weight and genome position and conserved motif analysis, was conducted. Expression analysis showed that 47 MsNACs had tissue-specific expression, and 64 MsNACs were expressed in all tissues. The transcriptomic profiles of the genes were very different, indicating that these MsNACs have various functions in alfalfa growth and development. We identified 25, 42 and 47 MsNACs that respond to cold, drought and salt stress based on transcriptome data analysis and real-time quantitative PCR (RT–qPCR). Furthermore, 22 MsNACs were found to respond to both salt and drought stress, and 15 MsNACs were found to respond to cold, salt and drought stress. The results of this study could provide valuable information for further functional analysis of MsNACs and for the improvement of stress resistance in alfalfa.