bluuebunny/crossref_metadata_2025 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.
Student Evaluation Using an Intellectual Standards Rubric for Critical Thinking
Authors: Johnson David , Kakar Rishtya , Zahrndt Robin , Walton Pete
Published: February 2022

Development of critical thinking skills is an important outcome in education, though pedagogies to both promote and evaluate critical thinking present challenges and vary greatly. In this article, we describe the development and use of a formative and generalizable rubric that leverages the Paul-Elder model for critical thinking, and in particular, Intellectual Standards. When used consistently, this Intellectual Standards Rubric for Critical Thinking (ISRCT) provides regular and specific insight to students about strengths and weaknesses, related to critical thinking, that are reflected in their work. The ISRCT can also be used to assess multiple components of the same assignment, which allows instructors to measure critical thinking competency development in greater detail and provide this feedback to students. Though Public Health is the discipline and context for the development and application of this evaluation methodology, the ISRCT is adapted from an agnostic critical thinking framework and model, and thus, could be utilized for a variety of disciplines and diverse assignments.
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

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

According 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

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

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

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

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

Background

Older 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.

Methods

Using 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.

Results

Models 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.

Conclusions

The 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

Background

Given 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.

Methods

This 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.

Results

On 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.

Conclusions

These 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

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

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.
Initial and ten-year treatment patterns among 11,000 breast cancer patients undergoing breast surgery—an analysis of German claims data
Authors: Heinig Miriam , Heinze Franziska , Schwarz Sarina , Haug Ulrike
Published: February 2022

Background

We aimed to explore the potential of German claims data for describing initial and long-term treatment patterns of breast cancer patients undergoing surgery.

Methods

Using the German Pharmacoepidemiological Research Database (GePaRD, ~ 20% of the German population) we included patients with invasive breast cancer diagnosed in 2008 undergoing breast surgery and followed them until 2017. We described initial and long-term treatment patterns and deaths. Analyses were stratified by stage (as far as available in claims data), age at diagnosis, and mode of detection (screen-detected vs. interval vs. unscreened cases).

Results

The cohort comprised 10,802 patients. The proportion with neoadjuvant therapy was highest in patients < 50 years (19% vs. ≤ 8% at older ages). The proportion initiating adjuvant chemotherapy within four months after diagnosis decreased with age (< 50 years: 63%, 50–69: 46%, 70–79: 27%, 80 + : 4%). Among women < 69 years, ~ 30% had two breast surgeries in year one (70–79: 21%, 80 + : 14%). Treatment intensity was lower for screen-detected compared to interval or unscreened cases, both in year one (e.g., proportion with mastectomy ~ 50% lower) and within 2–10 years after surgery (proportions with radiotherapy or chemotherapy about one third lower each).

Conclusions

This study illustrates the potential of routine data to describe breast cancer treatment and provided important insights into differences in initial and long-term treatment by mode of detection and age.
Treatment responses for branch retinal vein occlusion predicted by semi-automated fluorescein angiography quantification
Authors: Huang Pei-Wei , Lai Chi-Chun , Hwang Yih-Shiou , Wu Wei-Chi , Wu Cheng-Hsiu , Huang Jerry Chien-Chieh , Chen Yen-Po , Liu Laura , Chen Kuan-Jen , Yeung Ling
Published: February 2022

Backgrounds

Branch retinal vein occlusion (BRVO) is one of the most important causes of visual loss in retinal vascular diseases. The aim of this study is to predict the treatment response of anti-vascular endothelial growth factor (anti-VEGF) therapy in BRVO using semi-automated quantified fluorescein angiography (FA) features.

Methods

This retrospective case-control study enrolled patients with BRVO who are receiving anti-VEGF therapy and have been followed up for > 1 year. Those receiving < 5 anti-VEGF injections in the first year were classified as the responsive group, while those receiving ≥5 injections were the refractory group. The FA images were subjected to semi-automated pre-processing. Fluorescein leakages at the 5-min image were represented by mean gray value over parafoveal and perifoveal regions. FA leakages and central retinal thickness (CRT) on optical coherence tomography (OCT) were used for predicting the treatment response and compared using area under receiver operating characteristic curve (AUC).

Results

Eighty-nine patients (56 males, 33 females, mean age 62.5 ± 10.9 years) with BRVO were enrolled. Of the 89 eyes, 47 (53%) were in the responsive group and 42 (47%) were in the refractory group. The refractory group had a significantly higher number of anti-VEGF injections in the first year (5.9 ± 1.6 versus 2.4 ± 1.2,p < 0.001) when compared with that of the responsive group. It had thicker pre-treatment CRT (p = 0.011), post-treatment best CRT (p < 0.001) and CRT at 1-year (p < 0.001). It also had a higher mean gray value over the parafoveal (p < 0.001) and the perifoveal (p < 0.001) regions. The mean gray value over perifoveal (AUC 0.846) and parafovel (AUC 0.818) had significantly larger AUC than that of the pre-treatment OCT (AUC 0.653;p = 0.005 andp = 0.016, respectively) when predicting treatment response.

Conclusion

The refractory group had a more severe fluorescein leakage over the parafoveal and the perifoveal regions than the responsive group had. Semi-automated quantified FA leakage can be used as a biomarker for the prediction of anti-VEGF treatment response in macular edema due to BRVO.
Ocular biometry with swept-source optical coherence tomography-based optical biometer in Japanese patients with EYS-related retinitis pigmentosa: a retrospective study
Authors: Sakai Daiki , Yokota Satoshi , Maeda Akiko , Hirami Yasuhiko , Nakamura Makoto , Kurimoto Yasuo
Published: February 2022

Background

This study aimed to identify the features of ocular biometry in patients with EYS-related retinitis pigmentosa using IOLMaster 700.

Methods

We retrospectively reviewed the medical records of patients with retinitis pigmentosa. Patients with records of the following were included: (1) ocular biometry measurements using the IOLMaster 700 and (2) genetic diagnostic tests. Axial length, keratometry, anterior chamber depth, aqueous depth, lens thickness, central corneal thickness (CCT), and corneal diameter (white to white) measurements were extracted. Based on keratometry measurements, (1) standard keratometric astigmatism, (2) posterior corneal astigmatism, and (3) total corneal astigmatism were obtained. Demographics and biometric parameters were compared between patients with EYS-related retinitis pigmentosa and other patients with retinitis pigmentosa.

Results

A total of 86 eyes of 44 patients (23 females and 21 males; mean age: 47.7 years) with retinitis pigmentosa were included. Of these, 18 were identified as having EYS variants. CCT was significantly thinner (P < 0.001) and the posterior corneal curvature at the steepest meridian was significantly smaller (P = 0.024) in patients with EYS-related retinitis pigmentosa than in other patients with retinitis pigmentosa. The magnitudes of all corneal astigmatism measurements was higher in patients with EYS-related RP, although these differences were not statistically significant.

Conclusion

Patients with EYS-related retinitis pigmentosa had unique features in ocular biometry, such as thinner central corneal thickness and smaller posterior corneal curvature radius at the steepest meridian compared with other patients with retinitis pigmentosa. The findings suggest that patients with retinitis pigmentosa have different ocular dimension features among the different causative genes.
The essential conditions needed to implement the Indigenous Youth Mentorship Program: a focused ethnography
Authors: Sobierajski Frances , Lévesque Lucie , McGavock Jonathan , Beardy Tamara , Montemurro Genevieve ,   the IYMP National Team, Sobierajski Frances , Lévesque Lucie , McGavock Jonathan , Beardy Tamara , Storey Kate , Storey Kate
Published: February 2022

Background

The Indigenous Youth Mentorship Program (IYMP) is a 20-week communal, relationship-based afterschool healthy living program for Indigenous youth in Canada. IYMP embraces the Anishnaabe/Nehiyawak concepts of Mino-Bimaadiziwin/miyo-pimâtisiwin (“living in a good way”) via its core components of physical activities/games, healthy snacks, and relationship-building. A strength of IYMP is that it values autonomy, adaptability, and the school community context. However, this presents challenges when evaluating its implementation, given that traditional implementation science methods tend to oversimplify the process. In response, essential conditions for the implementation of school-based healthy living programs across diverse contexts have been developed. The purpose of this research was to understand the applicability of these essential conditions within the context of IYMP.

Methods

15 participants (n = 10 Young Adult Health Leaders; n = 5 coordinators) with experience implementing IYMP in the provinces of Alberta, Saskatchewan, Manitoba, and Quebec were purposefully sampled. Focused ethnography was the guiding method and one-on-one semi-structured interviews were used as the data generation strategy. The purpose of the interviews was to understand what conditions are needed to implement IYMP. The interview guide was based on previously established essential conditions developed by the research team. Interviews were audio-recorded and transcribed, and content analysis was used to identify patterns in the data.

Results

The overarching theme that emerged from the interviews was the applicability of the essential conditions when implementing IYMP. Participants felt the eight core conditions (students as change agents, school/community-specific autonomy, demonstrated administrative leadership, higher-level support, dedicated champion(s) to engage school community, community support, quality and use of evidence, and professional development) and four contextual conditions (time, funding and project support, readiness and understanding, and prior community connectivity) were necessary, but made suggestions to modify two conditions (youth led and learning opportunities) to better reflect their experiences implementing IYMP. In addition, a new core condition, rooted in relationship, emerged as necessary for implementation.

Conclusions

This research adds to the literature by identifying and describing what is needed in practice to implement a communal, relationship-based afterschool healthy living program. The essential conditions may support other researchers and communities interested in implementing and rippling similar programs.
Surgical interventions for Bertolotti’s syndrome: case report and review of unsatisfactory cases in the literature
Authors: Chang Chun-Jen , Chiu You-Pen , Ji Hui-Ru , Chu Chang-Hung , Chiu Cheng-Di
Published: February 2022

Background

Bertolotti’s syndrome (BS) is characterized by the enlargement of transverse processes in caudal lumbar segments, causing chronic and persistent low back pain or sciatica. The present study aimed to describe our surgical technique for BS treatment and to review existing literature describing unsatisfactory outcomes.

Case presentation

We report a patient who complained of lower back pain and soreness that intermittently radiated to his left leg for longer than 10 years. Based on an examination of his symptoms and signs, including imaging and electrical physiology assessments, in addition to the report of temporary pain relief after a local steroid injection to a diagnostic trigger site (articulation between the transverse process and the sacral ala or iliac crest), the patient was diagnosed with BS. The applied surgical techniques included minimally invasive, three-dimensional C-arm guidance, a tubing approach, and microscopic and bone cavitron ultrasonic surgical aspirator–assisted operations. After surgery, improvements were reported on the visual analog scale (from 8 to 2 points on a 10-point scale) and the straight leg raising test for the left leg (20° to 90°) within 3 days. The patient gained an ordinary life and returned to work within one week of surgery, with no observed postoperative complications.

Conclusions

Minimally invasive tubular microscopic decompression and disarticulation is an effective method for treating BS. However, to achieve a successful outcome, it is recommended to use physician-proficient techniques that are in line with the patient’s diagnosis.
A patient with 47, XYY mosaic karyotype and congenital absence of bilateral vas deferens: a case report and literature review
Authors: Zou Ci , Yu Dexin , Geng Hao , Lan Xiaofeng , Sun Wei
Published: February 2022

Background

The incidence of 47, XYY syndrome in live-born male infants is 1/1000. Due to its variable clinical symptoms, the diagnosis is easy to miss. The incidence of congenital bilateral absence of the vas deferens (CBAVD) in infertile men is 1–2%. The main cause is the mutation of CFTR and ADGAG2 genes.

Case presentation

The patient was a 33-year-old man who visited a doctor 5 years ago due to infertility. The investigation revealed that the patient’s secondary sexual characteristics, testicular, and penis development were normal, and there was no gynecomastia, but the bilateral vas deferens and epididymis were not palpable. Transrectal ultrasound showed that the left seminal vesicle was missing, and the right seminal vesicle was atrophied. No abnormality was observed in Y chromosome microdeletion. Karyotype analysis indicated that the patient was 46, XY/47, XYY mosaic. Genetic testing found heterozygous mutations at two sites of CFTR (c263T > G and c2249C > T).

Conclusions

Herein, we report the rare case of a male patient with clinical manifestations of infertility, chromosome 46, XY/47, XXY mosaic type, simultaneously manifested as the absence of bilateral vas deferens. Two pathogenic heterozygous CFTR gene mutations were found. Given the low genetic risk of the disease, we recommend that patients undergo intracytoplasmic sperm injection (ICSI) for fertility assessment.
Rapid prototyping-assisted tooth autotransplantation is associated with a reduced root canal treatment rate: a retrospective cohort study
Authors: Hwang Lisa Alice , Chang Chi-Yuan , Su Wei-Chia , Chang Chi-Wha , Huang Chien-Yu
Published: February 2022

Background

Autotransplantation is a beneficial treatment with a high success rate for young patients. However, most adult patients require root canal treatment (RCT) of the donor teeth after the autotransplantation procedure, which causes a prolonged treatment time and additional expenses and increases the rate of future tooth fracture. Rapid prototyping (RP)-assisted autotransplantation shortens the extra-alveolar time and enables a superior clinical outcome. However, no cohort studies of the application of this method on adult populations have been reported.

Methods

This study is a retrospective cohort study. All patients underwent autotransplantation from 2012 to 2020 in the Kaohsiung and Chia-Yi branches of Chang Gung Memorial Hospital, and the procedure and clinical outcomes were analysed. Differences in clinical outcomes, age, sex, extra-alveolar time, fixation method, and RCT rate were compared between the two groups.

Results

We enrolled 21 patients, 13 treated using the conventional method and 8 treated using the RP-based technique. The RCT rates of the conventional group and RP group were 92.3% and 59%, respectively. The mean age of the two groups was significantly different (28.8 ± 10 vs. 21.6 ± 2.1); after performing subgroup analysis by excluding all of the patients aged > 40 years, we found that the RCT rates were still significantly different (91.0% vs. 50%). The mean extra-alveolar time was 43 s in the RP group, and the autotransplantation survival rate in both groups was 100%.

Conclusions

Rapid prototyping-assisted autotransplantation was successfully adopted for all patients in our study population. By shortening the extra-alveolar time, only 50% of the patients required a root canal treatment with a 100% autotransplantation survival rate.

Trial Registration : Retrospectively registered.
Internal medicine residents’ perceptions and experiences in palliative care: a qualitative study in the United Arab Emirates
Authors: Harhara Thana , Abdul Hay Dana , Almansoori Dalal S. , Ibrahim Halah
Published: February 2022

Background

Palliative medicine is a newly developing field in the United Arab Emirates (UAE). The purpose of this study was to gain a deeper understanding of the experiences of internal medicine residents providing end-of-life care to patients and their families, and how those experiences shape their learning needs.

Method

Nine focus groups were conducted with internal medicine residents and recent graduates from two large academic health centers in the UAE between 2019 and 2020. Through an iterative process, data were collected and examined using constant comparison to identify themes and explore their relationships.

Results

Fifty-two residents and graduates participated. Residents frequently care for terminally ill patients and their families, but lack confidence in their skills and request more structured education and training. Cultural and system related factors also impact palliative care education and patient care. Five main themes and associated subthemes were identified: (1) clinical management of palliative patients, (2) patient and family communication skills, (3) religion, (4) barriers to end-of-life education, and (5) emotional impact of managing dying patients.

Conclusion

Our findings can help guide program development and curricular changes for internal medicine residents in the region. Structured education in end-of-life care, with a focus on fostering culturally sensitive communication skills and spirituality, can improve resident education and patient care. Clear and transparent policies at the institution level are necessary. Programs are also needed to assist residents in developing effective coping strategies and emotionally navigating experiences with patient death.
Network pharmacology and in vitro studies reveal the pharmacological effects and molecular mechanisms of Shenzhi Jiannao prescription against vascular dementia
Authors: Tian Danfeng , Gao Qiang , Chang Ze , Lin Jingfeng , Ma Dayong , Han Zhenyun
Published: February 2022

Background

Shenzhi Jiannao (SZJN) prescription is a type of herbal formula adopted in the management of cognitive impairment and related disorders. However, its effects and related regulatory mechanisms on vascular dementia (VD) are elusive. Herein, network pharmacology prediction was employed to explore the pharmacological effects and molecular mechanisms of SZJN prescription on VD using network pharmacology prediction, and validated the results through in vitro experiments.

Methods

Through a search in the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) database, chemical composition and targets for SZJN prescription were retrieved. The potential targets for VD were then obtained from the GeneCards and DisGeNET databases. The network was constructed that depicted the interactions between putative SZJN prescription and known therapeutic targets for VD using Cytoscape 3.7.1. Analysis of protein-protein interaction was achieved via STRING 11.0 software, followed by Gene Ontology (GO) functional enrichment and Kyoto Gene and Genome Encyclopedia (KEGG) pathway analyses. To validate the computer-predicted results, in vitro experiments based on an excitotoxic injury model were designed using glutamate-exposed PC12 cells, and treated with varying concentrations (low, 0.05; medium, 0.1 and high, 0.2 mg/mL) of SZJN prescription. Cell viability and cell death were detected using the IncuCyte imaging system. Moreover, the expression profiles of Caspase-3 were analyzed through qRT-PCR.

Results

Twenty-eight potentially active ingredients for SZJN prescription, including stigmasterol, beta-sitosterol, and kaempferol, plus 21 therapeutic targets for VD, including PTGS2, PTGS1, and PGR were revealed. The protein-protein interaction network was employed for the analysis of 20 target proteins, including CASP3, JUN, and AChE. The enrichment analysis demonstrated candidate targets of SZJN prescription were more frequently involved in neuroactive ligand-receptor interaction, calcium, apoptosis, and cholinergic synaptic signaling pathways. In vitro experiments revealed that SZJN prescription could significantly reverse glutamate-induced cell viability loss and cell death, and lower the levels of Caspase-3 mRNA in glutamate-induced PC12 cells.

Conclusions

Collectively, this study demonstrated that SZJN prescription exerted the effect of treating VD by regulating multi-targets and multi-channels with multi-components through the method of network pharmacology. Furthermore, in vitro results confirmed that SZJN prescription attenuated glutamate-induced neurotoxicity.
DNMT1 facilitates growth of breast cancer by inducing MEG3 hyper-methylation
Authors: Zhu Xiaotao , Lv Lin , Wang Mingzheng , Fan Chen , Lu Xiaofeng , Jin Miaomiao , Li Shuguang , Wang Fan
Published: February 2022

Background

To understand the effect of DNMT1-mediated MEG3 promoter methylation on breast cancer progression.

Methods

Expression of DNMT1, MEG3 and miR-494-3p was assayed by qRT-PCR and western blot. Methylation-specific PCR was used to examine MEG3 promoter methylation level. ChIP, RNA binding protein immunoprecipitation assay and dual-luciferase reporter gene assay were applied to verify interaction between DNMT1 and MEG3, miR-494-3p and MEG3 and OTUD4. CCK-8, wound healing and Transwell assays were used to detect biological functions of breast cancer cells. Tumor growth was observed by tumor xenograft model.

Results

DNMT1 and miR-494-3p were highly expressed while MEG3 and OTUD4 were lowly expressed in breast cancer cells. Knockdown of DNMT1 inhibited progression of breast cancer cells by enhance MEG3 expression through demethylation. MEG3 could downregulate miR-494-3p expression, and OTUD4 was a target of miR-494-3p. Upregulation of MEG3 and downregulation of miR-494-3p both inhibited malignant behavior of cells in vitro. In addition, high MEG3 expression restrained growth of breast cancer in vivo.

Conclusion

Briefly, our results demonstrated that, DNMT1 induced methylation of MEG3 promoter, and played a key role in breast cancer growth throughmiR-494-3p/OTUD4 axis. These findings provide new insights into molecular therapeutic targets for breast cancer.