bluuebunny/crossref_metadata_2025_split huggingface dataset:
Protocatechuic Aldehyde Alleviates d-Galactose–Induced Cardiomyocyte Senescence by Regulating the TCF3/ATG5 Axis
Authors: Wang Pengjun , Zhang Qingxiang 
Published: January 2023

Abstract:
Cardiomyocyte senescence is an independent risk factor for cardiovascular diseases. Protocatechuic aldehyde (PCA) is a natural chemical in the Chinese medicinal herb Salvia miltiorrhiza. PCA could protect against oxidative stress and inflammation in the cardiovascular system. In present study, we treated H9C2 cells with d-galactose to establish an in vitro model of cardiomyocyte senescence and investigated the role and underlying mechanisms of PCA in myocardial cell senescence. It was found that d-galactose induced transcription factor 3 (TCF3) expression and decreased autophagy-related genes 5 (ATG5) expression. Meanwhile, inflammation and senescence were exacerbated by d-galactose. TCF3 transcriptionally inhibited ATG5 expression. TCF3 knockdown abolished the effects of d-galactose on H9C2 by activating ATG5-mediated autophagy. PCA hindered TCF3 and inflammation to alleviate the d-galactose–induced senescence of H9C2 cells in a dose-dependent manner. Whereas, the anti-inflammation and anti-senescence effects of PCA were reversed by TCF3 knockdown. Furthermore, absence of ATG5 partially eliminated the impacts of PCA on H9C2 cells treated with d-galactose. Conclusively, PCA alleviated d-galactose–induced senescence by downregulating TCF3, promoting ATG5-mediated autophagy, and inhibiting inflammation in H9C2 cells. These results elucidated the potential mechanism by which PCA alleviated cardiomyocyte senescence and enabled its application in treating cardiomyocyte senescence.
circNFXL1 Modulates the Kv2.1 Channel Function in Hypoxic Human Pulmonary Artery Smooth Muscle Cells via Sponging miR-29b-2-5p as a Competitive Endogenous RNA
Authors: Li Shan-Shan , Liang Shuang , Li Lu , Yang Houzhi , Long Yao , Zhuo Donghai , Chen Xu , Jin Xin 
Published: January 2023

Abstract:
Pulmonary arterial hypertension is characterized by abnormal pulmonary vasoconstriction and vascular remodeling caused by the dysregulation of K+ channels in PA smooth muscle cells (PASMCs). However, how the K+ channels are dysregulated is still unclear. Circular RNAs (circRNAs) are noncoding RNAs with a closed-loop structure capable of sponging microRNAs (miRs), thus regulating gene expression at the post-transcriptional level. Our previous studies have demonstrated the importance of one novel circRNA (hsa_circNFXL1_009, circNFXL1) in pulmonary arterial hypertension patients, playing as a critical regulator for K+ channel activation in hypoxic human PASMCs (hPASMCs). Here, we explore the mechanisms underlying circNFXL1-regulated K+ channel expression and functions in hypoxic hPASMCs. In cultured hPASMCs, the reduction of Kv current induced by hypoxia was significantly recovered by delivering exogenous circNFXL1. Moreover, luciferase, quantitative reverse transcription-quantitative polymerase chain reaction, western blot, and mutagenesis studies confirmed that circNFXL1 reversed hypoxia-induced inhibitory effects on the Kv2.1 channel via sponging hsa-miR-29b-2-5p (miR-29b-2). Furthermore, we found that circNFXL1 reversed the miR-29b-induced Kv2.1 channel dysfunction at the whole-cell and single-channel level in HEK cells using a patch-clamp. Finally, calcium imaging revealed that hypoxia also triggered a substantial rise in the cytosolic calcium concentration ([Ca2
+
]cyt) in hPASMCs, and this hypoxia-induced elevation of [Ca2
+
]cyt was reduced by circNFXL1 through miR-29b-2. These data suggested that circNFXL1-mediated regulation of the Kv2.1 channel activation and the related intracellular calcium concentration may contribute to the effects of hypoxic pulmonary vasoconstriction.
Quantification of the Conjugated Forms of Dichlorobisphenol A (3,3′-Cl2BPA) in Rat and Human Plasma Using HPLC-MS/MS
Authors: Plattard Noemie , Gnanasegaran Riciga , Krekesheva Aida , Carato Pascal , Dupuis Antoine , Migeot Virginie , Albouy Marion , Haddad Sami , Venisse Nicolas 
Published: January 2023

Background:
Bisphenol A (BPA) is a ubiquitous contaminant that has endocrine-disrupting effects. Chlorinated derivatives of BPA are formed during chlorination of drinking water and have higher endocrine-disrupting activity. Dichlorobisphenol A (Cl2BPA) is the most abundant chlorinated BPA derivative found in several human biological matrices. Recent in vitro experiments have shown that Cl2BPA is metabolized in sulpho- and glucuro-conjugated compounds. To date, no assay has been developed to quantify the sulfo- and glucuro-conjugates of 3,3′-Cl2BPA (3,3′-Cl2BPA-S and 3,3′-Cl2BPA-G, respectively).

Methods:
A high-performance liquid chromatography-tandem mass spectrometry assay for the determination of 3,3′-Cl2BPA conjugated forms in plasma samples was developed and validated according to the European Medicines Agency guidelines. Quantification was performed in the multiple reaction monitoring mode for all target analytes using a SCIEX 6500 + tandem mass spectrometer with an electrospray source operating in the negative ionization mode. Chromatographic separation was achieved using a C18 column maintained at 40°C and a binary mobile phase delivered in the gradient mode at a flow rate of 0.35 mL/min. Sample was prepared via simple precipitation using acetonitrile. The assay was validated and applied to rat and human plasma samples.

Results:
Linearity was demonstrated over the range of 0.006–25 ng/mL for 3,3′-Cl2BPA-G and 0.391–100 ng/mL for 3,3′-Cl2BPA-S. Intraday and interday bias values were in the 95%–109% range, and the imprecision <9%. Internal standard corrected matrix effects were also investigated. This method enabled quantification of the conjugated forms of 3,3′-Cl2BPA in plasma samples.

Conclusions:
This is the first report on the development and validation of an analytical method for the quantification of 3,3′-Cl2BPA-G and 3,3′-Cl2BPA-S in the plasma matrix. This study is also the first report on the in vivo occurrence of these metabolites.
The impact of right atrial pressure on outcomes in patients undergoing TIPS, an ALTA group study
Authors: Bommena Shoma , Mahmud Nadim , Boike Justin R. , Thornburg Bartley G. , Kolli Kanti P. , Lai Jennifer C. , German Margarita , Morelli Giuseppe , Spengler Erin , Said Adnan , Desai Archita P. , Junna Shilpa , Paul Sonali , Frenette Catherine , Verna Elizabeth C. , Goel Aparna , Gregory Dyanna , Padilla Cynthia , VanWagner Lisa B. , Fallon Michael B. ,   on behalf of Advancing Liver Therapeutic Approaches (ALTA) Study Group
Published: January 2023

Background and Aims:
Single-center studies in patients undergoing TIPS suggest that elevated right atrial pressure (RAP) may influence survival. We assessed the impact of pre-TIPS RAP on outcomes using the Advancing Liver Therapeutic Approaches (ALTA) database.

Approach and Results:
Total 883 patients in ALTA multicenter TIPS database from 2010 to 2015 from 9 centers with measured pre-TIPS RAP were included. Primary outcome was mortality. Secondary outcomes were 48-hour post-TIPS complications, post-TIPS portal hypertension complications, and post-TIPS inpatient admission for heart failure. Adjusted Cox Proportional hazards and competing risk model with liver transplant as a competing risk were used to assess RAP association with mortality. Restricted cubic splines were used to model nonlinear relationship. Logistic regression was used to assess RAP association with secondary outcomes.
Pre-TIPS RAP was independently associated with overall mortality (subdistribution HR: 1.04 per mm Hg, 95% CI, 1.01, 1.08, p=0.009) and composite 48-hour complications. RAP was a predictor of TIPS dysfunction with increased odds of post-90-day paracentesis in outpatient TIPS, hospital admissions for renal dysfunction, and heart failure. Pre-TIPS RAP was positively associated with model for end-stage liver disease, body mass index, Native American and Black race, and lower platelets.

Conclusions:
Pre-TIPS RAP is an independent risk factor for overall mortality after TIPS insertion. Higher pre-TIPS RAP increased the odds of early complications and overall portal hypertensive complications as potential mechanisms for the mortality impact.
The association between hepatic steatosis and incident cardiovascular disease, cancer, and all-cause mortality in a US multicohort study
Authors: Ahmed Heidi S. , Wang Na , Carr J. Jeffrey , Ding Jingzhong , Terry James G. , VanWagner Lisa B. , Hou Lifang , Huo Yuankai , Palmisano Joseph , Zheng Yinan , Benjamin Emelia J. , Long Michelle T. 
Published: January 2023

Background and Aims:
NAFLD strongly associates with cardiovascular disease (CVD) risk factors; however, the association between NAFLD and incident CVD, CVD-related mortality, incident cancer, and all-cause mortality is unclear.

Approach and Results:
We included 10,040 participants from the Framingham Heart Study, the Coronary Artery Risk Development in Young Adults Study, and the Multi-ethnic Study of Atherosclerosis to assess the longitudinal association between liver fat (defined on CT) and incident CVD, CVD-related mortality, incident cancer, and all-cause mortality. We performed multivariable-adjusted Cox regression models including age, sex, diabetes, systolic blood pressure, alcohol use, smoking, HDL, triglycerides, and body mass index at baseline or time-varying covariates. The average age was 51.3±3.3 years and 50.6% were women. Hepatic steatosis was associated with all-cause mortality after 12.7 years of mean follow-up when adjusting for baseline CVD risk factors, including body mass index (HR: 1.21, 1.04–1.40); however, the results were attenuated when utilizing time-varying covariates. The association between hepatic steatosis and incident CVD was not statistically significant after we accounted for body mass index in models considering baseline covariates or time-varying covariates. We observed no association between hepatic steatosis and CVD-related mortality or incident cancer.

Conclusions:
In this large, multicohort study of participants with CT-defined hepatic steatosis, accounting for change in CVD risk factors over time attenuated associations between liver fat and overall mortality or incident CVD. Our work highlights the need to consider concurrent cardiometabolic disease when determining associations between NAFLD and CVD and mortality outcomes.
Improvement of clinical outcomes in patients undergoing peritoneal dialysis using hydroxymethylglutaryl-CoA reductase inhibitors: A systematic review and meta-analysis
Authors: Lee Dan-Ying , Huang Chi-Jung , Yeh Wan-Yu , Sung Shih-Hsien , Chen Chen-Huan , Cheng Hao-Min 
Published: January 2023

Background:
It is unclear whether hydroxymethylglutaryl-CoA reductase inhibitor (statin) therapy decreases the risk of mortality and cardiovascular disease (CVD) in patients undergoing peritoneal dialysis (PD).

Methods:
We performed a literature search of PubMed, Cochrane Library, Embase, and other databases for research publications up to June 2022. The outcomes of interest were fatal and nonfatal CVDs, all-cause mortality, and changes in the biochemical profiles. Hazard ratios (HRs) with 95% confidence intervals (CIs) were pooled and synthesized using a random-effects model. The certainty of the evidence was determined using Grading of Recommendations, Assessment, Development, and Evaluation.

Results:
Nine studies, including 2,933 patients undergoing PD, were included. Among them, three studies, including 2,099 patients, reported all-cause mortality, and three, including 1,571 patients, reported CVDs. In these patients, pooling results of two observational studies (very low-certainty evidence) showed that statin therapy significantly reduced CVDs (HR = 0.67; 95% CI = 0.54–0.84; p = 0.0004). Moreover, statin therapy was associated with significantly reduced low-density lipoprotein cholesterol, total cholesterol, and C-reactive protein levels (very low certainty of evidence). However, the effects of statin therapy on triglyceride, high-density lipoprotein, and albumin levels were not statistically significant.

Conclusion:
Although statin therapy was associated with significantly reduced low-density lipoprotein cholesterol, total cholesterol, and C-reactive protein levels, the probable beneficial effect of statins on CVD risk in patients undergoing PD could not be concluded firmly. Additional high-quality studies are required to assess the potential beneficial effects of statin therapy in PD patients.
Freezing nitrogen ethanol composite reduces periprosthetic infection caused by Staphylococcus aureus contaminated metal implants: An animal study
Authors: Chen Kuan-Lin , Chen Chao-Ming , Chen Yi-Chung , Wang Jir- You , Chen Cheng-Fong , Wu Po-Kuei , Chen Wei-Ming 
Published: January 2023

Background:
Implant-associated infection remains a major complication of orthopedic surgery. The treatment of such infection is complicated by bacterial biofilm formation on the metal surfaces of implants. Biofilm surrounds and protects the bacteria against the organism’s endogenous defense system and from external agents such as antibiotics and mechanical debridement. This study aims to evaluate whether freezing nitrogen ethanol composite (FNEC), the combination of liquid nitrogen and 95% ethanol in a 3 to 1 ratio, used frequently in bone tumor surgery, is capable of disinfecting Staphylococcus aureus contaminated implants.

Methods:
The femurs of six New Zealand white rabbits were implanted with S. aureus-contaminated screws, half of which were treated with FNEC before implantation. The femurs were harvested 14 days after implantation. Histological analysis and TUNEL assay were conducted. The autoclaved screw, contaminated screw, and FNEC-treated contaminated screw were investigated using scanning electron microscopy to evaluate the biofilm structure.

Results:
The FNEC-treated group had significantly lower relative C-reactive protein levels. An obvious periosteal reaction at the implant site was observed in all rabbits in the non-FNEC group but none was observed in the FNEC-treated group. The FNEC-treated group exhibited fewer empty lacunae, less inflammatory infiltration, and less bone necrosis. Immunohistochemical analysis showed no S. aureus in bone tissue from the FNEC-treated group. Scanning electron microscopy showed disruption of the biofilm on the contaminated screw treated with FNEC.

Conclusion:
FNEC showed potential in disinfecting S.aureus-contaminated implants. Further investigation is warranted, such as the effect on the implant-cement-bone interface, for FNEC to be used clinically in treating implant-associated infection.
Bone age assessment: Large-scale comparison of Greulich-Pyle method and Tanner-Whitehouse 3 method for Taiwanese children
Authors: Yuh Yeong-Seng , Chou Ting Ywan , Tung Tao-Hsin 
Published: January 2023

Background:
The Greulich-Pyle (GP) and Tanner-Whitehouse 3 (TW3) methods are two common methods for assessing bone age (BA). The applicability of these methods for populations other than those in the United States and Europe has been questioned. Thus, this study tested the applicability of these methods for Taiwanese children.

Methods:
In total, 1476 radiographs (654 boys, 822 girls) were analyzed. A subset of 200 radiographs was evaluated to determine intrarater and interrater reliability and the time required to yield a BA assessment. BA was determined by two reviewers using the GP method and two of the TW3 methods (the Radial-Ulnar-Short bones [RUS] method and the carpals method [Carpal]). The GP and TW3 methods were directly compared using statistical techniques. A subgroup analysis by age was performed to compare BA and chronological age using a paired t test for each age group.

Results:
The average times required to yield an assessment using the GP and TW3-RUS methods were 0.79 ± 0.14 and 3.01 ± 0.84 min (p < 0.001), respectively. Both the intrarater and interrater correlation coefficients were higher for the GP method (0.993, 0.992) than the TW3-RUS (0.985, 0.984) and TW3-Carpal (0.981, 0.973) methods. The correlation coefficient for the GP and TW3-RUS methods was highest in the pubertal stage (0.898 for boys and 0.909 for girls). The mean absolute deviations for the GP and TW3-RUS methods in the pubertal stage were 0.468 years (boys) and 0.496 years (girls). Both the GP and TW3-Carpal methods underestimated BA for boys in the prepubertal stage. Both the GP and TW3-RUS methods overestimated BA for girls in the pubertal and postpubertal stages.

Conclusion:
The GP and TW3-RUS methods exhibit strong agreement in the pubertal and postpubertal stages for both sexes. With appropriate adjustments based on Taiwanese data, both methods are applicable to our children.
Validity Properties of a Self-reported Modified Frailty Phenotype Among People With HIV in Clinical Care in the United States
Authors: Ruderman Stephanie A. , Webel Allison R. , Willig Amanda L. , Drumright Lydia N. , Fitzpatrick Annette L. , Odden Michelle C. , Cleveland John D. , Burkholder Greer , Davey Christine H. , Fleming Julia , Buford Thomas W. , Jones Raymond , Nance Robin M. , Whitney Bridget M. , Mixson L. Sarah , Hahn Andrew W. , Mayer Kenneth H. , Greene Meredith , Saag Michael S. , Kamen Charles , Pandya Chintan , Lober William B. , Kitahata Mari M. , Crane Paul K. , Crane Heidi M. , Delaney Joseph A. C. 
Published: January 2023

Abstract
Modifications to Fried's frailty phenotype (FFP) are common. We evaluated a self-reported modified frailty phenotype (Mod-FP) used among people with HIV (PWH). Among 522 PWH engaged in two longitudinal studies, we assessed validity of the four-item Mod-FP compared with the five-item FFP. We compared the phenotypes via receiver operator characteristic curves, agreement in classifying frailty, and criterion validity via association with having experienced falls. Mod-FP classified 8% of PWH as frail, whereas FFP classified 9%. The area under the receiver operator characteristic curve for Mod-FP classifying frailty was 0.93 (95% CI = 0.91–0.96). We observed kappa ranging from 0.64 (unweighted) to 0.75 (weighted) for categorizing frailty status. Both definitions found frailty associated with a greater odds of experiencing a fall; FFP estimated a slightly greater magnitude (i.e., OR) for the association than Mod-FP. The Mod-FP has good performance in measuring frailty among PWH and is reasonable to use when the gold standards of observed assessments (i.e., weakness and slowness) are not feasible.
Experiences of Underrepresented Racial Minorities in the Entry-Level Physical Therapy Education Application Process: A Conceptual Framework
Authors: Yeung Melissa 
Published: January 2023

Introduction.
The purpose of this study was to explore the experiences of Black and Latinx students as they navigate the entry-level physical therapy education program (PTEP) admissions process and how they made meaning of their experiences.

Review of Literature.
Existing literature is focused on quantitative aspects of the admissions process and on the applicant's potential for success within an entry-level PTEP. There is currently not enough evidence to provide the applicant perspective when navigating the entry-level physical therapy education admissions process.

Subjects.
A total of 11 participants were recruited from all entry-level PTEPs through social media sites and national student organizations for Black and Latinx students enrolled in entry-level PTEPs.

Methods.
Three interviews were conducted for each participant. Their responses were combined with a demographic survey received before the first. Interviews were then transcribed and coded with deductive and inductive processes.

Results.
The study yields a conceptual model for recruitment of Black and Latinx students. Factors for programs to consider include introduction to the profession, challenges and factors of support within the application process, and factors influencing enrollment decisions.

Discussion and Conclusion.
This exploratory study provides a roadmap to better understand the experiences and journey of Black and Latinx students to the field of physical therapy. Findings could be used by entry-level PTEPs to provide better access to information for prospective students.
Mirtazapine-induced Acute Pancreatitis in Patients With Depression: A Systematic Review
Authors: Milosavljević Miloš N. , Janković Slobodan M. , Kostić Marina J. , Pejčić Ana V. 
Published: January 2023

Objective:
Antidepressant-induced pancreatitis is a rare, albeit serious, adverse effect, with a frequency of occurrence that is not equally distributed among antidepressant drugs. The goal of this study was to investigate the association and causal relationship between mirtazapine treatment of patients with depression and pancreatitis.

Methods:
The study was designed as a systematic review of the literature, accompanied by the description of a new case of mirtazapine-associated acute pancreatitis.

Results:
Nine cases of mirtazapine-associated pancreatitis have been reported, involving 7 female patients and 2 male patients with a mean age of 46.4 years (range: 26 to 83 y of age). All of the patients were hospitalized, with an average length of stay of 16.2 days (range: 3 to 34 d). In 6 cases, “de-challenge” followed by improvement was reported. The patients for whom the outcome was reported (7 of 9) recovered completely.

Conclusion:
Although a rare adverse effect, mirtazapine-induced pancreatitis should be considered when patients taking mirtazapine report abdominal discomfort.
Using the Generic Analysis Method to Analyze Sentinel Event Reports Across Hospitals: A Retrospective Cross-Sectional Study
Authors: Baartmans Mees C. , Van Schoten Steffie M. , Smit Bert J. , Wagner Cordula 
Published: January 2023

Objectives
Improving patient safety by investigating sentinel events (SEs) is hampered by the focus on isolated events within hospitals and a narrow scope of traditional root cause analysis methods. We aimed to examine if performing cross-hospital aggregate analysis of SEs applying a novel generic analysis method (GAM) bearing a human factor perspective can enhance learning from SEs.

Methods
A retrospective cross-sectional review of SE reports from 28 Dutch general hospitals using the GAM to reanalyze events was performed. A qualitative approach was used to identify contributing factors and system issues. Findings were discussed with a patient safety expert panel. Descriptive statistics and measures of associations between domains were calculated.

Results
Sixty-nine SE reports were reviewed. Applying the GAM provided a more holistic SE analysis than a traditional method. Of the 405 identified contributing factors in all SEs, the majority was related to the persons involved (patients and professionals, n = 146 [36.2%]) and the organization (n = 121 [30%]). The most frequently recurring pattern was the combination of factors related to the persons involved, the technology used, the tasks of professionals, and organizational factors influencing the event. Cross-hospital aggregate GAM analysis of SEs helped to identify system issues and propose more system-oriented overarching recommendations.

Conclusions
This study found that applying the GAM to analyze SEs across hospitals can help to improve learning from SEs and may result in proposing stronger recommendations. The method can support hospitals, working together in a network of hospitals, to jointly learn from SEs.