bluuebunny/crossref_metadata_2025_split huggingface dataset:
Analysis of Return to Play After Modified Broström Lateral Ankle Ligament Reconstruction
Authors: May Nolan R. , Driscoll Matthew , Nguyen Shawn , Ferkel Richard D. 
Published: February 2022

Background: Despite marked improvements in stability after lateral ankle ligament repair, many patients do not return to their preinjury activity level. There are few studies addressing athletes’ assessment of their ability to return to play after lateral ankle ligament reconstruction for recurrent instability. Purpose: To determine the rate of return to the preinjury activity level among physically active patients after the modified Broström procedure (MBP) for recurrent lateral ankle instability. Study Design: Case series; Level of evidence, 4. Methods: Included were patients who had undergone a primary MBP by a single surgeon over a 6-year period and had a minimum 24 months of follow-up. A telephone questionnaire was conducted to ascertain the patient’s ability to return to sport and/or work activity at final follow-up. Activity levels were evaluated utilizing the Tegner activity score. Outcome scores and other measured variables were compared between patients who returned to their preinjury level and those who did not. The reasons for failing to return were also documented. Results: Of the 59 patients who met the inclusion criteria, 41 (69%; 20 men and 21 women) participated in the telephone interview. Results indicated that 22 (54%) returned to their prior level of activity (returners). The mean age of returners was 27.2 years; for nonreturners, the mean age was 27.1 years. Most patients (36/41; 88%) were satisfied with surgery and the overall outcome. Of the 19 nonreturners, 7 (37%) noted ankle-related reasons for not returning (pain: 57%; residual instability: 29%; decreased range of motion: 14%), and 12 (63%) cited non–ankle-related reasons. The mean preinjury and postoperative Tegner score for returners was 6.8. Moreover, 7 of 14 (50%) high-level athletes with preinjury Tegner scores ≥8 returned to their preinjury activity level. For high-level athletes who did not return to their previous level, the mean postoperative Tegner score was 6.6, and only 1 (7%) cited an ankle-related reason for not returning. Conclusion: A high patient satisfaction rate was reported after the MBP for recurrent lateral ankle instability. The majority of patients who did not return to their preinjury level cited a non–ankle-related factor as the reason for not returning to sport. This was especially true for the higher level athletes.
Scheduled administration of virus-specific T cells for viral prophylaxis after pediatric allogeneic stem cell transplant
Authors: Rubinstein Jeremy D. , Lutzko Carolyn , Leemhuis Thomas , Zhu Xiang , Pham Giang , Ray Lorraine , Thomas Shawn , Dourson Celeste , Wilhelm Jamie , Lane Adam , Cancelas Jose A. , Lipps Dakota , Ferrell Justin , Hanley Patrick J. , Keller Michael D. , Bollard Catherine M. , Wang YunZu M. , Davies Stella M. , Nelson Adam S. , Grimley Michael S. 
Published: February 2022

Abstract
Infections with double-stranded DNA viruses are a significant cause of morbidity and mortality in pediatric patients following allogeneic hematopoietic stem cell transplantation (HSCT). Virus-specific T-cell therapies (VSTs) have been shown to be an effective treatment for infections with adenovirus, BK virus, cytomegalovirus (CMV), and Epstein-Barr virus (EBV). To date, prophylactic regimens to prevent or mitigate these infections using conventional antiviral medications provide suboptimal response rates. Here we report on a clinical trial (NCT03883906) performed to assess the feasibility of rapid manufacturing and early infusion of quadrivalent VSTs generated from stem cell donors (“donor-derived VSTs”) into allogeneic HSCT recipients with minimal or absent viremia. Patients were eligible to receive scheduled VSTs as early as 21 days after stem cell infusion. Twenty-three patients received scheduled VSTs. Twenty of 23 patients had no viremia at the time of infusion, while 3 patients had very low-level BK viremia. Two developed clinically significant graft-versus-host disease (GVHD), although this incidence was not outside of expected incidence early after HSCT, and both were successfully treated with systemic corticosteroids (n = 2). Five patients were deemed treatment failures. Three developed subsequent significant viremia/viral disease (n = 3). Eighteen patients did not fail treatment, 7 of whom did not develop any viremia, while 11 developed low-level, self-limited viremia that resolved without further intervention. No infusion reactions occurred. In conclusion, scheduled VSTs appear to be safe and potentially effective at limiting serious complications from viral infections after allogeneic transplantation. A randomized study comparing this scheduled approach to the use of VSTs to treat active viremia is ongoing.
An input–output analysis of unit labour cost developments of the German manufacturing sector since the mid-1990s
Authors: Albu Nora , Joebges Heike , Zwiener Rudolf 
Published: February 2022

AbstractAccording to empirical studies, a statistically significant factor for German exports success is high cost (or price) competitiveness. Studies by Deutsche Bundesbank recommend correcting the nominal effective exchange rate by broad cost (or price) indicators (Deutsche Bundesbank, 1998, 2016a). This would call for total economy unit labour costs. In contrast to these findings, Dustmann et al. (2014) suggest using refined unit labour costs for the exporting manufacturing sector only, corrected for inputs from other sectors and from abroad in an Input–Output (IO) analysis framework. According to these authors’ novel calculation, the export-oriented manufacturing sector of Germany experienced a decrease in unit labour costs by 25% between the mid-1990s and 2007. We try to replicate their findings. Following standard approaches in calculating sectoral unit labours costs, correcting for inputs from other sectors and from abroad, and using consistent input–output data from the Federal Statistical Office and from the World Input–Output Database, nominal unit labour costs of the manufacturing sector did not decrease over the period of analysis, and developed similarly to total unit labour costs. The similarity to total economy costs is also confirmed for a more recent period. In contrast to these authors’ claim, our findings are in line with recommendations of Deutsche Bundesbank for using total economy unit labour costs.
RNA secondary structure prediction with convolutional neural networks
Authors: Saman Booy Mehdi , Ilin Alexander , Orponen Pekka 
Published: February 2022

Abstract
Background
Predicting the secondary, i.e. base-pairing structure of a folded RNA strand is an important problem in synthetic and computational biology. First-principle algorithmic approaches to this task are challenging because existing models of the folding process are inaccurate, and even if a perfect model existed, finding an optimal solution would be in general NP-complete.

Results
In this paper, we propose a simple, yet effective data-driven approach. We represent RNA sequences in the form of three-dimensional tensors in which we encode possible relations between all pairs of bases in a given sequence. We then use a convolutional neural network to predict a two-dimensional map which represents the correct pairings between the bases. Our model achieves significant accuracy improvements over existing methods on two standard datasets, RNAStrAlign and ArchiveII, for 10 RNA families, where our experiments show excellent performance of the model across a wide range of sequence lengths. Since our matrix representation and post-processing approaches do not require the structures to be pseudoknot-free, we get similar good performance also for pseudoknotted structures.

Conclusion
We show how to use an artificial neural network design to predict the structure for a given RNA sequence with high accuracy only by learning from samples whose native structures have been experimentally characterized, independent of any energy model.
SPL9 mediates freezing tolerance by directly regulating the expression of CBF2 in Arabidopsis thaliana
Authors: Zhao Junli , Shi Min , Yu Jing , Guo Changkui 
Published: February 2022

Abstract
Background
Freezing stress inhibits plant development and causes significant damage to plants. Plants therefore have evolved a large amount of sophisticated mechanisms to counteract freezing stress by adjusting their growth and development correspondingly. Plant ontogenetic defense against drought, high salt, and heat stresses, has been extensively studied. However, whether the freezing tolerance is associated with ontogenetic development and how the freezing signals are delivered remain unclear.

Results
In this study, we found that the freezing tolerance was increased with plant age at the vegetative stage. The expressions of microRNA156 (miR156) and SQUAMOSA PROMOTER BINDING PROTEIN-LIKE 9 (SPL9), playing roles in regulation of ontogenetic development, were induced by cold stress. Overexpression of SPL9 (rSPL9) promoted the expression of C-REPEAT BINDING FACTOR 2 (CBF2) and hereafter enhanced the freezing tolerance. Genetic analysis indicated that the effect of rSPL9 on freezing tolerance is partially restored by cbf2 mutant. Further analysis confirmed that SPL9 directly binds to the promoter of CBF2 to activate the expression of CBF2, and thereafter increased the freezing tolerance.

Conclusions
Therefore, our study uncovers a new role of SPL9 in fine-tuning CBF2 expression and thus mediating freezing tolerance in plants, and implies a role of miR156-SPL pathway in balancing the vegetative development and freezing response in Arabidopsis.
MiR-138-5p targets RUNX2 to inhibit osteogenic differentiation of aortic valve interstitial cells via Wnt/β-catenin signaling pathway
Authors: Yan Fei , Huo Qiang , Zhang Weimin , Wu Tingting , Dilimulati Daniyaer , Shi Lin 
Published: February 2022

Abstract
Background
Human aortic valve interstitial cells (hAVICs) are a key factor in the pathogenesis of calcific aortic valve disease (CAVD). This research examines the role and mechanism of microRNA miR-138-5p in osteogenic differentiation of hAVICs.

Methods
RT-qPCR analysis was applied for detecting miR-138-5p and RUNX2 expression in valve tissues of CAVD patients and controls. On completion of induction of osteogenic differentiation of hAVICs, and after overexpression or interference of miR-138-5p expression, the condition of osteogenic differentiation and calcification of hAVICs was confirmed using alkaline phosphatase staining and alizarin red staining. Subsequently, western blot was utilized to detect the expression of osteogenesis-related proteins OPN and ALP, and Wnt/β-catenin signaling pathway-related proteins. Finally, the relationship between miR-138-5p and RUNX2 was validated by dual-luciferase reporter assay and Pearson’s correlation test.

Results
Down-regulation of miR-138-5p was found in CAVD patients and during osteogenic differentiation of hAVICs. Overexpression of miR-138-5p contribute to the inhibition of osteoblast differentiation and calcium deposition in hAVICs, and of ALP and OPN protein expression. RUNX2 was a target gene of miR-138-5p, and it was negatively correlated with miR-138-5p in CAVD. Additionally, overexpression of RUNX2 could reverse the inhibitory effect of miR-138-5p on osteogenic differentiation of hAVICs.

Conclusion
miR-138-5p can act as a positive regulator of osteogenic differentiation in CAVD patients to involve in inhibiting valve calcification, which is achieved through RUNX2 and Wnt/β-catenin signaling pathway.
Secondary prevention of rheumatic heart disease in Ethiopia: a multicenter study
Authors: Belay Wubishet , Dessie Azene , Ahmed Hayat , Gedlu Etsegenet , Mariyo Abinet , Shehibo Abdulkadir , Tigabu Zemene , Aliyu Muktar H. , Soslow Jonathan 
Published: February 2022

Abstract
Background
Ethiopia has a high acute rheumatic fever (ARF) and rheumatic heart disease (RHD) prevalence, and to our knowledge, there are no data on the status of secondary prevention in children with RHD. This study describes the status of secondary RHD prevention.

Methods
A multicenter, prospective study was performed on children aged 5–17 years with RHD in Ethiopia. Good adherence was defined as at least 80% completion of benzathine penicillin (BPG) or oral Amoxicillin within the previous year. The primary outcome measure was adherence to prophylaxis, expressed as a proportion. Socio-demographics, severity of RHD, and ARF recurrence were evaluated.

Results
A total of 337 children with a mean age of 12.9 ± 2.6 years were included. The majority (73%) had severe aortic/mitral disease. Participants were on BPG (80%) or Amoxicillin (20%) prophylaxis. Female sex (P = 0.04) use of BPG (0.03) and shorter mean duration of prophylaxis in months (48.5 ± 31.5 vs. 60.7 ± 33, respectively, P < 0.008) predicted good adherence. Running out of medications (35%), interrupted follow-up (27%), and the COVID-19 pandemic (26%) were the most common reasons for missing prophylaxis. Recurrence of ARF was higher in participants on Amoxicillin compared with BPG (40% vs. 16%, P < 0.001) and in those with poor adherence compared with good adherence (36.8% vs. 17.9%, respectively, P = 0.005). Type and duration of prophylaxis (OR 0.5, CI = 0.24, 0.9, P = 0.02; OR = 1.1, CI = 1.1, 1.2, P = 0.04, respectively), and sex (OR = 1.9, CI = 1.1, 3.4, P = 0.03) were independent predictors of poor adherence.

Conclusion
Poor adherence is prevalent in Ethiopian children living with RHD. Amoxicillin is a suboptimal option for prophylaxis as its use is associated with lower adherence and a higher rate of ARF recurrence.
Predicting hand washing, mask wearing and social distancing behaviors among older adults during the covid-19 pandemic: an integrated social cognition model
Authors: Duan Yanping , Shang Borui , Liang Wei , Lin Zhihua , Hu Chun , Baker Julien Steven , Wang Yanping , He Jiali 
Published: February 2022

AbstractBackgroundOlder adults are at a higher risk from COVID-19. Individual preventive behaviors including frequent hand washing, mask wearing, and social distancing play important roles in reducing the transmission of COVID-19 in the community. This study aimed to identify the determinants of three preventive behaviors of older adults during the COVID-19 pandemic by using an Integrated Social Cognition Model.MethodsUsing a prospective study design, 516 Chinese older adults from Hubei province of China (mean age = 67.55 years, SD = 6.60, 57.9% females) completed two online questionnaire surveys. The demographics, social cognition constructs (motivational self-efficacy, risk perception, attitude, subjective norm, health knowledge, intention, volitional self-efficacy, planning, action control) and three preventive behaviors were measured during the first-wave online survey from 18 May 2020 to 7 June 2020. One month later, three preventive behaviors were measured again during the second-wave online survey. Data were analyzed by structural equation modelling.ResultsModels showed attitude, motivational self-efficacy and subjective norm were consistent predictors of intention, motivational self-efficacy was a consistent predictor of volitional self-efficacy, planning and volitional self-efficacy were consistent predictors of action control, and health knowledge was a consistent predictor of behaviors across all three preventive behaviors. In addition, mediating relationships were found in the model of hand washing behavior. In particular, planning (β = .109,p= .042) and action control (β = .056,p= .047) mediated between volitional self-efficacy and hand washing respectively. Action control also mediated between planning and hand washing (β = .087,p= .044). Moreover, the inclusion of past behaviors in three models attenuated most of the structural relations.ConclusionsThe current study’s findings basically supported the Integrated Social Cognition Model and identified key modifiable determinants of preventive behaviors. Based on this model, future interventions aiming to promote COVID-19 preventive behaviors among older adults are warranted.
Identifying solutions to meet unmet needs of family caregivers using human-centered design
Authors: Termglinchan Vittavat , Daswani Samira , Duangtaweesub Paricha , Assavapokee Taweevat , Milstein Arnold , Schulman Kevin 
Published: February 2022

AbstractBackgroundGiven the rapidly aging society, shrinking workforce, and reducing dependency ratio, there is an increasing challenge for family members to provide care for older adults. While a broad understanding of caregiver burden and its consequences have been studied across various contexts, there is a need to better understand this challenge among family caregivers in Asian societies.MethodsThis study is a cross-sectional observational study. A total of 20 dyads of community-based older adults, who required assistance with at least one activities of daily living, and family caregivers in Thailand participated in the study. We used the first three stages out of five stages of human-centered design: empathize, define, and ideate.ResultsOn average caregivers were 59.2 years old, with 43% still employed. Of the older adult participants, 10 were interviewed, the others had moderate-to-severe cognitive impairment. Based on the analysis, six caregiver personas (i.e. semi-fictional characters) are identified. Caregiver personas of “The 2-Jober” and “My Life Purpose” has the highest caregiver burden score whereas “The Spouse” has the lowest. Based on the specific needs of the caregiver persona “My Life Purpose”, the team brainstormed more than 80 potential solutions which were classified into three categories of solutions that satisfied the metrics of desirability, feasibility and viability: distributed medical care system, technology-charged care network, and community gathering for rest and recuperation.ConclusionsThese solutions are culturally sensitive given that they are built around established behavioral patterns. This is an illustration of a method of innovation that can be applied to bring a culturally specific understanding, and to develop products and services to enable further independent aging.
Longitudinal monitoring of mRNA levels of regulatory T cell biomarkers by using non-invasive strategies to predict outcome in renal transplantation
Authors: Canossi Angelica , Iesari Samuele , Lai Quirino , Ciavatta Simone , Del Beato Tiziana , Panarese Alessandra , Binda Barbara , Tessitore Alessandra , Papola Franco , Pisani Francesco 
Published: February 2022

Abstract
Background
Acute T-cell mediated rejection (aTCMR) is still an issue in kidney transplantation, for it is associated with chronic rejection, graft loss, and overall worse outcomes. For these reasons, a standard non-invasive molecular tool to detect is desirable to offer a simpler monitoring of kidney transplant recipients (KTRs). The purpose of our study was to examine, in peripheral blood before and after transplantation, the expression patterns of regulatory T cell (Treg)-related genes: the forkhead box P3 (FOXP3) and the two CTLA-4 isoforms (full-length and soluble) to predict acute rejection onset, de novo donor-specific antibodies (DSA) development and renal dysfunction 1 year after transplantation.

Methods
We profiled by using a relative quantification analysis (qRT-PCR) circulating mRNA levels of these biomarkers in peripheral blood of 89 KTRs within the first post-transplant year (at baseline and 15, 60 and 365 days, and when possible at the acute rejection) and compared also the results with 24 healthy controls.

Results
The three mRNA levels drastically reduced 15 days after transplantation and gradually recovered at 1 year in comparison with baseline, with very low levels at the time of aTCMR for FOXP3 (RQ = 0.445, IQR = 0.086–1.264, p = 0.040), maybe for the pro-apoptotic role of FOXP3 during inflammation. A multivariate Cox regression analysis evidenced a significant relation between aTCMR onset and thymoglobuline induction (HR = 6.749 p = 0.041), everolimus use (HR = 7.017, p = 0.007) and an increased risk from the solCTLA-4 expression at 15 days, mainly considering recipients treated with Mycophelolic acid (HR = 13.94 p = 0.038, 95%CI:1.157–167.87). Besides, solCTLA-4 also predisposed to graft dysfunction (eGFR< 60 mL/min/1.73m2) at 1 year (AOR = 3.683, 95%CI = 1.145–11.845, p = 0.029). On the other hand, pre-transplant solCTLA-4 levels showed a protective association with de novo DSAs development (HR = 0.189, 95%CI = 0.078–0.459, p < 0.001).

Conclusions
mRNA levels of Treg-associated genes, mainly for solCTLA-4, in peripheral blood could put forward as candidate non-invasive biomarkers of cellular and humoral alloreactivity in clinical transplantation and might help shape immunosuppression, tailor monitoring and achieve better long-term outcomes of kidney transplantation in the wake of “precision medicine”.
Pre-clinical and clinical studies on the role of RBM3 in muscle-invasive bladder cancer: longitudinal expression, transcriptome-level effects and modulation of chemosensitivity
Authors: Wahlin Sara , Boman Karolina , Moran Bruce , Nodin Björn , Gallagher William M. , Karnevi Emelie , Jirström Karin 
Published: February 2022

Abstract
Background
The response to neoadjuvant cisplatin-based chemotherapy (NAC) in muscle-invasive bladder cancer (MIBC) is impaired in up to 50% of patients due to chemoresistance, with no predictive biomarkers in clinical use. The proto-oncogene RNA-binding motif protein 3 (RBM3) has emerged as a putative modulator of chemotherapy response in several solid tumours but has a hitherto unrecognized role in MIBC.

Methods
RBM3 protein expression level in tumour cells was assessed via immunohistochemistry in paired transurethral resection of the bladder (TURB) specimens, cystectomy specimens and lymph node metastases from a consecutive cohort of 145 patients, 65 of whom were treated with NAC. Kaplan-Meier and Cox regression analyses were applied to estimate the impact of RBM3 expression on time to recurrence (TTR), cancer-specific survival (CSS), and overall survival (OS) in strata according to NAC treatment. The effect of siRNA-mediated silencing of RBM3 on chemosensitivity was examined in RT4 and T24 human bladder carcinoma cells in vitro. Cellular functions of RBM3 were assessed using RNA-sequencing and gene ontology analysis, followed by investigation of cell cycle distribution using flow cytometry.

Results
RBM3 protein expression was significantly higher in TURB compared to cystectomy specimens but showed consistency between primary tumours and lymph node metastases. Patients with high-tumour specific RBM3 expression treated with NAC had a significantly reduced risk of recurrence and a prolonged CSS and OS compared to NAC-untreated patients. In high-grade T24 carcinoma cells, which expressed higher RBM3 mRNA levels compared to RT4 cells, RBM3 silencing conferred a decreased sensitivity to cisplatin and gemcitabine. Transcriptomic analysis revealed potential involvement of RBM3 in facilitating cell cycle progression, in particular G1/S-phase transition, and initiation of DNA replication. Furthermore, siRBM3-transfected T24 cells displayed an accumulation of cells residing in the G1-phase as well as altered levels of recognised regulators of G1-phase progression, including Cyclin D1/CDK4 and CDK2.

Conclusions
The presented data highlight the potential value of RBM3 as a predictive biomarker of chemotherapy response in MIBC, which could, if prospectively validated, improve treatment stratification of patients with this aggressive disease.