bluuebunny/crossref_metadata_2025_split huggingface dataset:
miR-146a-5p Promotes Chondrocyte Apoptosis and Inhibits Autophagy of Osteoarthritis by Targeting NUMB
Authors: Zhang Hongjun , Zheng Wendi , Li Du , Zheng Jia 
Published: July 2021

Objective miR-146a-5p was found to be significantly upregulated in cartilage tissue of patients with osteoarthritis (OA). NUMB was shown to be involved in the autophagy regulation process of cells. We aimed to learn whether NUMB was involved in the apoptosis or autophagy process of chondrocytes in OA and related with miR-146a-5p. Methods QRT-PCR was used to detect miR-146a-5p level in 22 OA cartilage tissues and 22 controls. The targets of miR-146a-5p were analyzed using software and the luciferase reporter experiment. The apoptosis and autophagy, and related proteins were detected in chondrocytes treated with miR-146a-5p mimic/inhibitor or pcDNA3.1-NUMB/si-NUMB and IL-1β, respectively. In vivo experiment, intra-articular injection of miR-146a-5p antagomir/NC was administered at the knee of OA male mice before and after model construction. Chondrocyte apoptosis and the expression of apoptosis and autophagy-related proteins were also detected. Results miR-146a-5p was highly expressed in knee cartilage tissue of patients with OA, while NUMB was lowly expressed and negatively regulated by miR-146a-5p. Upregulation of miR-146a-5p can promote cell apoptosis and reduce autophagy of human and mouse chondrocytes by modulating the levels of cleaved caspase-3, cleaved PARP, Bax, Beclin 1, ATG5, p62, LC3-I, and LC3-II. Increasing the low level of NUMB reversed the effects of miR-146a-5p on chondrocyte apoptosis and autophagy. Intra-articular injection of miR-146a-5p antagomir can also reverse the effects of miR-146a-5p on the apoptosis and autophagy of knee joint chondrocytes in OA mice. Conclusion Downregulation of miR-146a-5p suppresses the apoptosis and promotes autophagy of chondrocytes by targeting NUMB in vivo and in vitro.
Utility of St. George’s respiratory questionnaire in predicting clinical recurrence in chronic pulmonary aspergillosis
Authors: Bongomin Felix , Otu Akaninyene 
Published: July 2021

Background and Aims: Patients with chronic pulmonary aspergillosis (CPA) who discontinue antifungal therapy commonly exhibit disease recurrence. We aimed to evaluate the utility of the St. George’s respiratory questionnaire (SGRQ) in predicting the likelihood of clinical recurrence of CPA in patients who come off antifungal therapy. Methods: This audit included CPA patients for whom antifungal therapy was discontinued for at least 1 month. Comparisons were made between the quality of life scores at the time of discontinuation of treatment and at the time of diagnosis of clinical recurrence. The change in patients’ self-assessment scores was also compared. Results: There were 33 cases and 44 controls. Of the 33 cases, 22 (67%) were males with a mean age of 62 ± 13 years. The median for the symptom component of quality of life (QoL) changed from 78.4 at the time of discontinuation of therapy to 83.1 units at the time of diagnosis of clinical failure ( p = 0.043), whereas that of the impact and activity components changed from 62.7 to 59.1 units ( p = 0.387) and 85.0 to 85.9 units ( p = 0.153), respectively. At 12 months, the symptoms domain of SGRQ was able to discriminate between cases of clinical recurrence and controls [area under the curve (AUC) 0.7, 95% confidence interval (CI): 0.6–0.8, p = 0.009]. The proportion of patients in very poor health status increased from 3/11 (9.1%) to 11/33 (33.3%) ( p = 0.046). Conclusion: A deteriorating symptoms component of the SGRQ and a worsening of patients’ self-assessment are associated with clinical recurrence. Failure to improve by >8 units in the symptoms domain appear to be a marker of disease recurrence. We propose that the clinical approach to diagnose recurrent CPA would be a combination of clinical history, SGRQ scoring, chest imaging and a workup to exclude other causes of the patients’ symptoms.
The utility of a dual-phase, dual-energy CT protocol in patients presenting with overt gastrointestinal bleeding
Authors: Mohammadinejad Payam , Kwapisz Lukasz , Fidler Jeff L , Sheedy Shannon P , Heiken Jay P , Khandelwal Ashish , Wells Michael L , Froemming Adam T , Hansel Stephanie L , Lee Yong S , Inoue Akitoshi , Halaweish Ahmed F , McCollough Cynthia H , Bruining David H , Fletcher Joel G 
Published: July 2021

Background Due to their easy accessibility, CT scans have been increasingly used for investigation of gastrointestinal (GI) bleeding. Purpose To estimate the performance of a dual-phase, dual-energy (DE) GI bleed CT protocol in patients with overt GI bleeding in clinical practice and examine the added value of portal phase and DE images. Materials and Methods Consecutive patients with GI bleeding underwent a two-phase DE GI bleed CT protocol. Two gastroenterologists established the reference standard. Performance was estimated using clinical CT reports. Three GI radiologists rated confidence in GI bleeding in a subset of 62 examinations, evaluating first mixed kV arterial images, then after examining additional portal venous phase images, and finally after additional DE images (virtual non-contrast and virtual monoenergetic 50 keV images). Results 52 of 176 patients (29.5%) had GI bleeding by the reference standard. The overall sensitivity, specificity, and positive and negative predictive values of the CT GI bleed protocol for detecting GI bleeding were 65.4%, 89.5%, 72.3%, and 86.0%, respectively. In patients with GI bleeding, diagnostic confidence of readers increased after adding portal phase images to arterial phase images ( p = 0.002), without additional benefit from dual energy images. In patients without GI bleeding, confidence in luminal extravasation appropriately decreased after adding portal phase, and subsequently DE images ( p = 0.006, p = 0.018). Conclusion A two-phase DE GI bleed CT protocol had high specificity and negative predictive value in clinical practice. Portal venous phase images improved diagnostic confidence in comparison to arterial phase images alone. Dual-energy images further improved radiologist confidence in the absence of bleeding.
Elderly Patients in Primary Care are Still at Risks of Receiving Potentially Inappropriate Medications
Authors: Vatcharavongvan Pasitpon , Puttawanchai Viwat 
Published: July 2021

Background Most older adults with comorbidities in primary care clinics use multiple medications and are at risk of potentially inappropriate medications (PIMs) prescription. Objective This study examined the prevalence of polypharmacy and PIMs using Thai criteria for PIMs. Methods This study was a retrospective cross-sectional study. Data were collected from electronic medical records in a primary care clinic in 2018. Samples were patients aged ≥65 years old with at least 1 prescription. Variables included age, gender, comorbidities, and medications. The list of risk drugs for Thai elderly version 2 was the criteria for PIMs. The prevalence of polypharmacy and PIMs were calculated, and multiple logistic regression was conducted to examine associations between variables and PIMs. Results Of 2806 patients, 27.5% and 43.7% used ≥5 medications and PIMs, respectively. Of 10 290 prescriptions, 47% had at least 1 PIM. The top 3 PIMs were anticholinergics, proton-pump inhibitors, and nonsteroidal anti-inflammatory drugs (NSAIDs). Polypharmacy and dyspepsia were associated with PIM prescriptions (adjusted odds ratio 2.48 [95% confident interval or 95% CI 2.07-2.96] and 3.88 [95% CI 2.65-5.68], respectively). Conclusion Prescriptions with PIMs were high in the primary care clinic. Describing unnecessary medications is crucial to prevent negative health outcomes from PIMs. Computer-based clinical decision support, pharmacy-led interventions, and patient-specific drug recommendations are promising interventions to reduce PIMs in a primary care setting.
Clinical and Radiographic Outcomes of Total Shoulder Arthroplasty With a Nonspherical Humeral Head and Inlay Glenoid in Elite Weight Lifters: A Prospective Case Series
Authors: Yalcin Sercan , Scarcella Michael , Everhart Joshua , Samuel Linsen , Miniaci Anthony 
Published: July 2021

Background: Weight lifting after total shoulder arthroplasty (TSA) can place significant stresses on implants that could lead to instability, loosening, and increased wear. A TSA system with nonspherical humeral head resurfacing and inlay glenoid—which improves the biomechanics and thus reduces instability, wear, and potential loosening—may be able to tolerate repetitive loads from weight lifting. Purpose: To determine clinical and radiographic outcomes after TSA in weight lifters. Study Design: Case series; Level of evidence, 4. Methods: We prospectively enrolled 16 weight lifters (mean ± SD age, 57.2 ± 7.8 years; 15 male) undergoing primary anatomic TSA (n = 17 shoulders, 1 staged bilateral) with nonspherical humeral head resurfacing and inlay glenoid replacement for glenohumeral osteoarthritis between February 2015 and February 2019. Exclusion criteria were rotator cuff deficiency, revision TSA, post-traumatic arthritis, and inflammatory arthritis. Outcome measures included the rate of return to weight lifting, results of patient-reported outcome measures (Penn Shoulder Score, Kerlan-Jobe Orthopaedic Clinic, and 12-Item Veterans RAND Health Survey), radiographic outcomes, and complication rate. Results: Follow-up was obtained on all patients at a mean of 38 months (range, 14-63 months). All patients returned to competitive weight lifting at 15.6 ± 6.9 weeks. Compared to the preoperative weight lifting level, at last follow-up patients reported performance at the following level: lighter weight, 1 (6%); same weight, 8 (50%); heavier weight, 7 (44%). Preoperative eccentric posterior glenoid wear was common (71% Walch B2 classification; 12/17), but posterior humeral subluxation improved at follow-up according to the Walch index (mean, 55.5% preoperative vs 48.5% postoperative; P < .001) and contact point ratio (mean, 63.9% preoperative vs 50.1% postoperative; P < .001). Pre- to postoperative improvements were seen in Penn Shoulder Score (44.3 vs 82.6; P < .001), Kerlan-Jobe Orthopaedic Clinic (50.6 vs 91.1; P < .001), and 12-Item Veterans RAND Health Survey physical component score but not mental component score. No signs of radiographic loosening were detected in follow-up images, nor were there any postoperative instability episodes or revision surgeries. Conclusion: There were substantial improvements in shoulder function and a high rate of return to weight lifting after TSA with a nonspherical humeral head resurfacing and inlay glenoid component. Radiographically, the humeral head centralized on the glenoid after surgery, and there was no evidence of component loosening at a mean 38-month follow-up.
Using Visual Aids to Supplement Medical Instructions, Health Education, and Medical Device Instructions
Authors: Lee Katherine , Nathan-Roberts Dan 
Published: July 2021

Objective: To review the effects of visual aids on adherence, comprehension, and recall when used to supplement written or spoken information in medical instructions, health education, and medical device instructions and the effects on patients with low literacy levels. Method: Review of studies from medical instructions, health education, and medical device instructions to measure adherence, comprehension, and recall of written or spoken instructions, with or without visual aids. Results: The addition of visual aids to written or spoken instructions can positively impact adherence, comprehension, and recall, which can lead to better patient outcomes. Simpler, larger, quantitative, regional, and reinforcing visual aids provided the largest improvements, especially with patients with low literacy.
Privacy, or the Lack Thereof, and Its Implications for Dignity in Mobile COVID-19 Testing
Authors: Neely Jennifer , Eddins Amani , Lesure Naomi , Dee Danielle , Real Raquel , Singer Rebecca , Crooks Natasha , Singer Randi B. 
Published: July 2021

Introduction Chicago’s COVID-19 Rapid Response Team (CRRT) is a decentralized, interprofessional group of nurses, residents, students, and faculty who provide free COVID-19 testing for those living or working in congregate settings (i.e., shelters, long term care facilities, prisons and encampments) due to their increased risk. Individuals within these vulnerable populations regularly experience stigma, a lack of privacy, and healthcare discrimination as they are often in low-income and underserved communities. The CRRT tests in settings that are necessarily large (cafeterias, meeting areas, gymnasiums, recreation rooms), and provide little physical privacy. Regardless of patient circumstances, respecting patient dignity is a professional standard of care, and patient privacy is consistent with that standard. Methods Guided by trauma-informed care techniques, emancipatory nursing practice, and cultural safety methodology, student members of the CRRT initiated a project focused on expanding physical privacy protection for those undergoing COVID-19 testing. Conclusion Though the introduction of a portable privacy screen started as an initiative to safeguard the dignity for underserved populations, this call to action implores current and future health care providers to prioritize the ethical treatment of those most vulnerable by advocating for patient dignity and privacy.
Genome-wide DNA methylation pattern in systemic sclerosis microvascular endothelial cells: Identification of epigenetically affected key genes and pathways
Authors: Nada Shadia , Kahaleh Bashar , Altorok Nezam 
Published: July 2021

Background: The etiology of systemic sclerosis is not clear, but there is evidence suggesting a critical role for epigenetic alterations in disease pathogenesis and clinical expression. We sought, in this study, to characterize the genome-wide DNA methylation signature in systemic sclerosis microvascular endothelial cells. Methods: We performed a genome-wide DNA methylation study in microvascular endothelial cells derived from seven diffuse cutaneous systemic sclerosis patients compared to seven age-, sex-, and ethnicity-matched healthy controls. We paired matched samples on Illumina HumanMethylation450 (three diffuse cutaneous systemic sclerosis microvascular endothelial cells and three controls), and reproduced the results in an independent set of matched patient and controls using Illumina Infinium MethylationEPIC (four diffuse cutaneous systemic sclerosis patients and four controls) to identify differentially methylated genes. Results: We identified 71,353 differentially methylated CpG sites in systemic sclerosis microvascular endothelial cells using Infinium MethylationEPIC microarray in the first group (0.081% of representative probes) and 33,170 CpG sites in the second group using HumanMethylation450 microarray (0.073% of representative probes) in diffuse cutaneous systemic sclerosis microvascular endothelial cells. Among the two groups of subjects, we identified differential methylation of 2455 CpG sites, representing 1301 genes. Most of the differentially methylated CpG sites were hypermethylated (1625 CpG), corresponding to 910 genes. Common hypermethylated genes in systemic sclerosis microvascular endothelial cells include NOS1, DNMT3A, DNMT3B, HDAC4, and ANGPT2. We also identified hypomethylation of IL17RA, CTNNA3, ICAM2, and SDK1 in systemic sclerosis microvascular endothelial cells. Furthermore, we demonstrate significant inverse correlation between DNA methylation status and gene expression in the majority of genes evaluated. Gene ontology analysis of hypermethylated genes demonstrated enrichment of genes involved in angiogenesis ( p = 0.0006). Pathway analysis of hypomethylated genes includes genes involved in vascular smooth muscle contraction ( p = 0.014) and adherens junctions ( p = 0.013). Conclusion: Our data suggest the presence of significant genome-wide DNA methylation aberrancies in systemic sclerosis microvascular endothelial cells, and identify novel affected genes and pathways in systemic sclerosis microvascular endothelial cells.
Resistance to Bruton tyrosine kinase inhibitors: the Achilles heel of their success story in lymphoid malignancies
Authors: Stephens Deborah M. , Byrd John C. 
Published: July 2021

Abstract
Bruton tyrosine kinase inhibitors (BTKi) have significantly changed the treatment landscape for patients with B-cell malignancies, including chronic lymphocytic leukemia, Waldenstrom macroglobulinemia, mantle cell lymphoma, and marginal zone lymphoma. Unfortunately, patients with BTKi-resistant disease have shortened survival. Clinical and molecular risk factors, such as number of prior therapies and presence of TP53 mutations, can be used to predict patients at the highest risk of developing BTKi resistance. Many mechanisms of BTKi resistance have been reported with mutations in BTK and phospholipase C γ2 supported with the most data. The introduction of venetoclax has lengthened the survival of patients with BTKi-resistant disease. Ongoing clinical trials with promising treatment modalities, such as next-generation BTKi and chimeric antigen receptor T-cell therapy, have reported promising efficacy in patients with BTKi-resistant disease. Continued research focusing on resistance mechanisms and methods of how to circumvent resistance is needed to further prolong the survival of patients with BTKi-resistant B-cell malignancies.
Comparisons within the Rice GA 2-Oxidase Gene Family Revealed Three Dominant Paralogs and a Functional Attenuated Gene that Led to the Identification of Four Amino Acid Variants Associated with GA Deactivation Capability
Authors: Hsieh Kun-Ting , Chen Yi-Ting , Hu Ting-Jen , Lin Shih-Min , Hsieh Chih-Hung , Liu Su-Hui , Shiue Shiau-Yu , Lo Shuen-Fang , Wang I-Wen , Tseng Ching-Shan , Chen Liang-Jwu 
Published: July 2021

Abstract
Background
GA 2-oxidases (GA2oxs) are involved in regulating GA homeostasis in plants by inactivating bioactive GAs through 2β-hydroxylation. Rice GA2oxs are encoded by a family of 10 genes; some of them have been characterized, but no comprehensive comparisons for all these genes have been conducted.

Results
Rice plants with nine functional GA2oxs were demonstrated in the present study, and these genes not only were differentially expressed but also revealed various capabilities for GA deactivation based on their height-reducing effects in transgenic plants. Compared to that of wild-type plants, the relative plant height (RPH) of transgenic plants was scored to estimate their reducing effects, and 8.3% to 59.5% RPH was observed. Phylogenetic analysis of class I GA2ox genes revealed two functionally distinct clades in the Poaceae. The OsGA2ox3, 4, and 8 genes belonging to clade A showed the most severe effect (8.3% to 8.7% RPH) on plant height reduction, whereas the OsGA2ox7 gene belonging to clade B showed the least severe effect (59.5% RPH). The clade A OsGA2ox3 gene contained two conserved C186/C194 amino acids that were crucial for enzymatic activity. In the present study, these amino acids were replaced with OsGA2ox7-conserved arginine (C186R) and proline (C194P), respectively, or simultaneously (C186R/C194P) to demonstrate their importance in planta. Another two amino acids, Q220 and Y274, conserved in OsGA2ox3 were substituted with glutamic acid (E) and phenylalanine (F), respectively, or simultaneously to show their significance in planta. In addition, through sequence divergence, RNA expression profile and GA deactivation capability analyses, we proposed that OsGA2ox1, OsGA2ox3 and OsGA2ox6 function as the predominant paralogs in each of their respective classes.

Conclusions
This study demonstrates rice has nine functional GA2oxs and the class I GA2ox genes are divided into two functionally distinct clades. Among them, the OsGA2ox7 of clade B is a functional attenuated gene and the OsGA2ox1, OsGA2ox3 and OsGA2ox6 are the three predominant paralogs in the family.
Dose approach matter? A meta-analysis of outcomes following transfemoral versus transapical transcatheter aortic valve replacement
Authors: Guo Ruikang , Xie Minghui , Yim Wai Yen , Wu Wenconghui , Jiang Weiwei , Wang Yin , Hu Xingjian 
Published: July 2021

Abstract
Background
Transcatheter aortic valve replacement (TAVR) has gained increasing acceptance for patients with aortic disease. Both transfemoral (TF-TAVR) and transapical (TA-TAVR) approach were widely adopted while their performances are limited to a few studies with controversial results. This meta-analysis aimed to compare the mortality and morbidity of complications between TF- versus TA-TAVR based on the latest data.

Methods
Electronic databases were searched until April 2021. RCTs and observational studies comparing the outcomes between TF-TAVR versus TA-TAVR patients were included. Heterogeneity assumption was assessed by an I2 test. The pooled odds ratios(OR) or mean differences with corresponding 95% confidence intervals (CI) were used to evaluate the difference for each end point using a fixed-effect model or random-effect model based on I2 test.

Results
The meta-analysis included 1 RCT and 20 observational studies, enrolling 19,520 patients (TF-TAVR, n = 11,986 and TA-TAVR, n = 7,534). Compared with TA-TAVR, TF-TAVR patients showed significantly lower rate of postoperative in-hospital death (OR = 0.67, 95% CI 0.59–0.77, P < 0.001) and 1-year death (OR = 0.53, 95% CI 0.41–0.69, P < 0.001). Incidence of major bleeding and acute kidney injury were lower and length of hospital stay was shorter, whereas those of permanent pacemaker and major vascular complication were higher in TF-TAVR patients. There were no significant differences between TF-TAVR versus TA-TAVR for stroke and mid-term mortality.

Conclusions
There were fewer early deaths in patients with transfemoral approach, whereas the number of mid-term deaths and stroke was not significantly different between two approaches. TF-TAVR was associated with lower risk of bleeding, acute kidney injury as well as shorter in-hospital stay, but higher incidence of vascular complication and permanent pacemaker implantation.