bluuebunny/crossref_metadata_2025_split huggingface dataset:
Foot and Ankle Injections in Athletes
Authors: Ochoa Jonathan K. , Gross Christopher E. , Anderson Robert B. , Hsu Andrew R. 
Published: March 2021

Context: Injections are commonly used by health care practitioners to treat foot and ankle injuries in athletes despite ongoing questions regarding efficacy and safety. Evidence Acquisition: An extensive literature review was performed through MEDLINE, Google Scholar, and EBSCOhost from database inception to 2021. Keywords searched were injections, athletes, sports, foot and ankle, corticosteroids, platelet-rich plasma, and placental tissue. Search results included articles written in the English language and encompassed reviews, case series, empirical studies, and basic science articles. Study Design: Clinical review. Level of Evidence: Level 4. Results: Corticosteroids, platelet-rich plasma/autologous blood, anesthetic, and placental tissue injections are commonly used in the treatment of foot and ankle injuries. Primary indications for injections in athletes include plantar fasciitis, Achilles tendinosis, isolated syndesmotic injury, and ankle impingement with varying clinical results. Conclusions: Despite promising results from limited case series and comparative studies, the data for safety and efficacy of injections for foot and ankle injuries in athletes remain inconclusive.
Review of the role of big data and digital technologies in controlling COVID-19 in Asia: Public health interest vs. privacy
Authors: Nageshwaran Gopinath , Harris Rebecca C , Guerche-Seblain Clotilde El 
Published: March 2021

Background Asia has been at the forefront of leveraging big data and digital technologies to strengthen measures against SARS-CoV-2 spread. Understanding strengths and challenges of these new approaches is important to inform improvements and implementation. In this review, we aimed to explore how these tools were utilized in four countries in Asia to facilitate COVID-19 preventative control measures. Methods We conducted a pragmatic review of English-language literature and web-based information in Pubmed, MedRxiv, national and international public health institution websites and media sources between 1st January-3rd August 2020 to identify examples of big data and digital technologies to facilitate COVID-19 preventative control measures in Taiwan, South Korea, Hong Kong, and Singapore. Results were summarized narratively by common technological themes, and examples of integration highlighted. Results Digital tools implemented included real-time epidemiological dashboards, interactive maps of case location, mobile apps for tracing patients’ contacts and geofencing to monitor quarantine compliance. Examples of integration of tools included linkage of national health and immigration databases to identify high-risk individuals in Taiwan, and the use of multiple digital surveillance sources to map patients’ movements in South Korea. Challenges in balancing privacy and public good were identified. Conclusions Digital technologies have facilitated and strengthened traditional public health measures for prevention of SARS-CoV-2 spread in Asia. Resolving issues around privacy concerns would improve future preparedness, implementation speed and uptake of digital measures. The significant technological advances and lessons learned can be adopted or adapted by other countries to ensure public health preparedness for future waves of COVID-19 and other pandemics.
Determinants of Workforce Preparedness during Pandemics Among Healthcare Workers at the U.S. Department of Veterans Affairs
Authors: Balut Michelle D. , Der-Martirosian Claudia , Dobalian Aram 
Published: March 2021

Objective: An infectious disease outbreak can place a significant burden on healthcare systems, however, our understanding of the broader healthcare workforce’s preparedness during a pandemic is limited. This study examines factors that influence perceived workforce preparedness at the U.S. Department of Veterans Affairs (VA) during a pandemic. Methods: The VA Preparedness Survey was a random, anonymous, web-based survey fielded nationwide October to December 2018. Multivariate statistical analyses examined the effects of study relevant factors (sociodemographic, work-related, general health, and household-related characteristics of VA employees) on perceptions of workforce preparedness, including institutional readiness and understanding of individual roles during a pandemic. Results: Four thousand and twenty-six VA employees responded. Overall, 55% were confident in their VA medical facility’s ability to respond; 49% understood their role; and 68% reported their role to be important during a pandemic. After controlling for study-relevant factors, household preparedness, having plans that address the health care needs of family members, and higher self-reported health status were associated with all 3 workforce preparedness variables. Clinical staff (compared to non-clinical staff) were less likely (OR:0.80, 95% CI:0.68-0.94, P < .01) to have confidence in their medical facility’s ability to respond but more likely (OR:1.77, 95% CI:1.49-2.10, P < .001) to believe their role was important. Employees who have been at the VA longer (OR:1.07, 95% CI:1.01-1.14, P < .05) or have experienced a disaster while working at the VA (OR:1.29, 95% CI:1.04-1.59, P < .05) were more likely to understand their role during a pandemic. Conclusion: The findings from this study suggest the need for identifying ways to increase VA employees’ confidence in their medical facility’s ability to respond to a pandemic; develop trainings to improve understanding of their different yet critical roles, for both clinical and non-clinical staff, during a pandemic; create different workforce trainings for newly hired employees; and identify ways to improve household preparedness for a pandemic outbreak.
Incidence of venous thromboembolism in Asian patients undergoing anterior cruciate ligament reconstruction without the use of mechanical or chemical prophylaxis
Authors: Liu Xuan , Tan Andrew Hwee Chye 
Published: March 2021

Background: Venous thromboembolism (VTE) is a clinically relevant complication of major orthopedic surgeries. The prevalence of VTE and the indications for VTE thromboprophylaxis in Asian patients undergoing arthroscopic anterior cruciate ligament (ACL) reconstruction are not clear. This study aims to evaluate the prevalence of clinically significant venous thromboembolic events (VTE) in Asian patients undergoing arthroscopic ACL reconstruction without mechanical or chemical thromboprophylaxis. Methods: All patients who underwent ACL reconstruction by a single surgeon from 2006 to 2018 in a single tertiary institution were reviewed. The inclusion criteria for the study included Asian patients of common ethnic groups in Singapore (Chinese, Malay, Indian) and underwent primary or revision ACL reconstruction, or ACL reconstruction combined with meniscal surgery. The exclusion criteria were patients with incomplete medical records, pre-existing anticoagulant treatment within 1 year prior to the surgery and additional procedures that altered the standard rehabilitation protocol, less than 6 months of follow-up duration. All patients received general anesthesia. The single-bundle ACL technique with autologous hamstring tendon reconstruction was performed. No chemical DVT prophylaxis was given. The patients were screened for clinically for VTE. Symptomatic patients were referred for ultrasonography. Results: Of the 581 patients reviewed, 3 patients had a clinical suspicion of deep vein thrombosis, but subsequent ultrasonography showed no thrombosis. Hence, the prevalence of clinically significant VTE was 0%. Conclusion: Given the low prevalence of clinically significant VTE, there is no need for routine mechanical or chemical thromboprophylaxis or radiologic screening in Asian patients undergoing arthroscopic ACL reconstruction.
Clinical outcomes after intracorneal ring segment implantation for keratoconus management in corneas with mild apical haze
Authors: Elalfy Mohamed , Maqsood Sundas , Reinhold Aja , Panos Georgios D. , Khine Aye , Lake Damian , Hamada Samer , Gatzioufas Zisis 
Published: March 2021

Purpose: The implantation of intracorneal ring segments represents an effective and safe therapeutic option for visual improvement in patients with keratoconus. The presence of corneal opacities is considered an exclusion criterion for this operation. Methods: This is a retrospective cohort study of six eyes of six keratoconus patients at Queen Victoria Hospital, East Grinstead, UK, between January 2012 and December 2016. Femtosecond laser-assisted intracorneal ring segment implantation was performed in six eyes with apical corneal haze. Preoperative and postoperative visual acuity, keratometry readings, as well as corneal pachymetry were compared at 6-month follow-up. Results: Uncorrected visual acuity (UCVA) [LogMAR] improved significantly from median 1.05 [95% confidence interval (CI): 0.83–0.13] preoperatively to 0.9 (95% CI: 0.63–1.00) at 6 months postoperatively ( p = 0.03). Corrected visual acuity (CDVA) also improved significantly from median 0.75 (95% CI: 0.43–1.00) preoperatively to 0.4 (95% CI: 0.23–0.50) at 6 months postoperatively ( p = 0.03). Keratometric readings, K-max (diopters) and K-mean (diopters), decreased significantly from 54.5 and 47.85 preoperatively to 53.45 and 46.42 postoperatively, respectively ( p = 0.03). Corneal pachymetry showed no significant changes postoperatively. Conclusion: The results of this study show that the presence of apical haze should not exclude the implantation of intracorneal ring segments in patients with keratoconus.
Natural variability in the disease course of SSc-ILD: implications for treatment
Authors: Vonk Madelon C. , Walker Ulrich A. , Volkmann Elizabeth R. , Kreuter Michael , Johnson Sindhu R. , Allanore Yannick 
Published: March 2021

Interstitial lung disease (ILD) affects approximately 50% of patients with systemic sclerosis (SSc) and is the leading cause of death in SSc. Our objective was to gain insight into the progression of SSc-associated ILD (SSc-ILD). Using data from longitudinal clinical trials and observational studies, we assessed definitions and patterns of progression, risk factors for progression, and implications for treatment.SSc-ILD progression was commonly defined as exceeding specific thresholds of lung function worsening and/or increasing radiographic involvement. One definition used in several studies is decline in forced vital capacity (FVC) of ≥10%, or ≥5–10% plus a decline in diffusing capacity of the lung for carbon monoxide ≥15%. Based on these criteria, 20–30% of patients in observational cohorts develop progressive ILD, starting early in the disease course and progressing at a highly variable rate.Risk factors such as age, FVC, extent of fibrosis and presence of anti-topoisomerase I antibodies can help predict progression of SSc-ILD, though composite risk scores may offer greater predictive power. Whilst the variability of the disease course in SSc-ILD makes risk stratification of patients challenging, the decision to initiate, change or stop treatment should be based on a combination of the current disease state and the speed of progression.
Estimates of the mean difference in orthopaedic randomized trials: obligatory yet obscure
Authors: Raittio Lauri , Launonen Antti , Mattila Ville M. , Reito Aleksi 
Published: March 2021

Abstract
Background
Randomized controlled trials in orthopaedics are powered to mainly find large effect sizes. A possible discrepancy between the estimated and the real mean difference is a challenge for statistical inference based on p-values. We explored the justifications of the mean difference estimates used in power calculations. The assessment of distribution of observations in the primary outcome and the possibility of ceiling effects were also assessed.

Methods
Systematic review of the randomized controlled trials with power calculations in eight clinical orthopaedic journals published between 2016 and 2019. Trials with one continuous primary outcome and 1:1 allocation were eligible. Rationales and references for the mean difference estimate were recorded from the Methods sections. The possibility of ceiling effect was addressed by the assessment of the weighted mean and standard deviation of the primary outcome and its elaboration in the Discussion section of each RCT where available.

Results
264 trials were included in this study. Of these, 108 (41 %) trials provided some rationale or reference for the mean difference estimate. The most common rationales or references for the estimate of mean difference were minimal clinical important difference (16 %), observational studies on the same subject (8 %) and the ‘clinical relevance’ of the authors (6 %). In a third of the trials, the weighted mean plus 1 standard deviation of the primary outcome reached over the best value in the patient-reported outcome measure scale, indicating the possibility of ceiling effect in the outcome.

Conclusions
The chosen mean difference estimates in power calculations are rarely properly justified in orthopaedic trials. In general, trials with a patient-reported outcome measure as the primary outcome do not assess or report the possibility of the ceiling effect in the primary outcome or elaborate further in the Discussion section.
Questionnaire-based detection of immune-related adverse events in cancer patients treated with PD-1/PD-L1 immune checkpoint inhibitors
Authors: Griewing Luisa Maria , Schweizer Claudia , Schubert Philipp , Rutzner Sandra , Eckstein Markus , Frey Benjamin , Haderlein Marlen , Weissmann Thomas , Semrau Sabine , Gostian Antoniu-Oreste , Müller Sarina K. , Traxdorf Maximilian , Iro Heinrich , Zhou Jian-Guo , Gaipl Udo S. , Fietkau Rainer , Hecht Markus 
Published: March 2021

Abstract
Background
Immune checkpoint inhibitors (ICI) have become standard treatment in different tumor entities. However, safe treatment with ICI targeting the PD-1/PD-L1 axis requires early detection of immune-related adverse events (irAE). There exist different questionnaires of drug manufacturers for the detection of irAE that have not been validated so far.

Methods
The prospective non-interventional ST-ICI trial studied treatment with PD-1/PD-L1 ICI alone or combined with radiotherapy. In the current analysis, the detection rate of self-reported irAE with a patient questionnaire containing 41 different questions was compared to clinician-reported irAE.

Results
Between April 2017 and August 2019, a total of 104 patients were prospectively enrolled. NSCLC (44%) and HNSCC (42%) were the most frequent tumor entities. A total of 784 questionnaires were collected. A total of 29 irAE were reported by clinicians. The most frequent irAE was hypothyroidism (9%), followed by skin reactions (5%), hepatitis (4%), diarrhea (3%), and pneumonitis (3%). Questions that became significantly more often positive at time points of clinician-reported irAE were “weight change”, “difficulty to grip things”, “bloody or mucous stool” and “insomnia”. Self-reported organ-specific questions detected at least 50% of clinician-reported irAE of gastrointestinal, lung, endocrine, and skin irAE. It was not possible to detect hepatic irAE with the questionnaire.

Conclusion
Questionnaires can help to detect gastrointestinal, lung, endocrine, or skin irAE, but not hepatic irAE. Questions on “weight change” and “insomnia” may help to increase the detection rate of irAE, besides organ-specific questions. These results are a valuable contribution to the future development of a specific and practicable questionnaire for early self-reported detection of irAE during ICI therapy in cancer patients.

Trial registration
ClinicalTrials.gov, NCT03453892. Registered on 05 March 2018.
Severe obesity in a specialist type 2 diabetes outpatient clinic: an Australian retrospective cohort study
Authors: Thakur Arunav , Sharma Dharmesh , Gupta Bhavya , Kramadhari Nikitha , Rajagopal Rohit , Simmons David , Piya Milan Kumar 
Published: March 2021

Abstract
Background
Obesity is a major risk factor for the development of type 2 diabetes (T2DM) and its complications. Significant weight loss has been shown to improve glycaemia in people with T2DM and obesity. National and international guidelines recommend considering bariatric surgery for body mass index (BMI) ≥ 35 kg/m2. We assessed the proportion of people with T2DM meeting criteria for surgery, how many had been offered a bariatric/obesity service referral, and compared the characteristics of people with BMI ≥ 35 kg/m2 and BMI < 35 kg/m2.

Methods
Retrospective data were collected for all people with T2DM aged ≥18 years, attending a hospital specialist diabetes outpatient service over three calendar years, 2017–2019.

Results
Of 700 people seen in the service, 291 (42%) had BMI ≥ 35 kg/m2 (the “BMI ≥ 35 group”) and met criteria for bariatric surgery, but only 54 (19%) of them were offered referral to an obesity service. The BMI ≥ 35 group was younger than those with a BMI < 35 kg/m2 (56.1 ± 14.8 vs 61.4 ± 14.6 years, p < 0.001) (mean ± SD), with similar diabetes duration (11.0 ± 9.0 vs 12.3 ± 8.9 years, p = 0.078), and there was no significant difference in initial HbA1c (75 ± 27 vs 72 ± 26 mmol/mol, p = 0.118) (9.0 ± 2.5 vs 8.7 ± 2.4%) or proportion treated with insulin (62% vs 58%). There was more GLP1 agonist use in the BMI ≥ 35 group (13% vs 7%, p = 0.003) but similar rates of SGLT2 inhibitor use (25% vs 21%, p = 0.202). The BMI ≥ 35 group received more new medication and/or dose adjustments (74% vs 66%, p = 0.016). Only 29% in the BMI ≥ 35 kg group achieved HbA1c < 53 mmol/mol (7.0%).

Conclusions
In spite of frequently meeting the criteria for bariatric surgery and not achieving glycaemic targets, people with T2DM in this specialist clinic received limited medical or surgical management of their obesity. This study suggests opportunities for improvement in care of people with T2DM at several levels including increased referrals from T2DM services to weight management/bariatric services, as well as an increased use of GLP1 agonists and SGLT2 inhibitors where appropriate. Our data support the need to prioritise obesity management in the treatment of type 2 diabetes.
Presence and activation of pro-inflammatory macrophages are associated with CRYAB expression in vitro and after peripheral nerve injury
Authors: Lim Erin-Mai F. , Hoghooghi Vahid , Hagen Kathleen M. , Kapoor Kunal , Frederick Ariana , Finlay Trisha M. , Ousman Shalina S. 
Published: March 2021

AbstractBackgroundInflammation constitutes both positive and negative aspects to recovery following peripheral nerve injury. Following damage to the peripheral nervous system (PNS), immune cells such as macrophages play a beneficial role in creating a supportive environment for regrowing axons by phagocytosing myelin and axonal debris. However, a prolonged inflammatory response after peripheral nerve injury has been implicated in the pathogenesis of negative symptoms like neuropathic pain. Therefore, the post-injury inflammation must be carefully controlled to prevent secondary damage while allowing for regeneration. CRYAB (also known as alphaB-crystallin/HSPB5) is a small heat shock protein that has many protective functions including an immunomodulatory role in mouse models of multiple sclerosis, spinal cord injury, and stroke. Because its expression wanes and rebounds in the early and late periods respectively after PNS damage, and CRYAB null mice with sciatic nerve crush injury display symptoms of pain, we investigated whether CRYAB is involved in the immune response following PNS injury.MethodsSciatic nerve crush injuries were performed in age-matchedCryabknockout (Cryab−/−) and wildtype (WT) female mice. Nerve segments distal to the injury site were processed by immunohistochemistry for macrophages and myelin while protein lysates of the nerves were analyzed for cytokines and chemokines using Luminex and enzyme-linked immunosorbent assay (ELISA). Peritoneal macrophages from the two genotypes were also cultured and polarized into pro-inflammatory or anti-inflammatory phenotypes where their supernatants were analyzed for cytokines and chemokines by ELISA and protein lysates for macrophage antigen presenting markers using western blotting.ResultsWe report that (1) more pro-inflammatory CD16/32+macrophages are present in the nerves ofCryab−/−mice at days 14 and 21 after sciatic nerve crush-injury compared to WT counterparts, and (2) CRYAB has an immunosuppressive effect on cytokine secretion [interleukin (IL)-β, IL-6, IL-12p40, tumor necrosis factor (TNF)-α] from pro-inflammatory macrophages in vitro.ConclusionsCRYAB may play a role in curbing the potentially detrimental pro-inflammatory macrophage response during the late stages of peripheral nerve regeneration.
Caveolin-1 is involved in encephalomyocarditis virus replication in BHK-21 cells
Authors: Li Qiongyi , Liu Yang , Xu Shujuan , Zhao Kexue , Ling Ying , Liu Rongxiu , Ali Amjad , Bai Jialin 
Published: March 2021

Abstract
Background
Encephalomyocarditis virus, member of Cardiovirus genus within Picornaviridae family, is an important pathogen that infects different domestic and wild animals. However, the molecular mechanism of its entry remains unclear. In this study, we investigated the mechanism of EMCV infectivity in relation to endocytic pathway using BHK-21 cells.

Methods
The function of numerous cellular key factors implicated in the various endocytic mechanisms were systematically explored using chemical inhibitors. Furthermore, RNA interference (RNAi) as well as the overexpression of dominant protein combined to virus infectivity assays, and confocal microscopy was used to examine EMCV infection in details.

Results
The results indicated that the EMCV entry into BHK-21 cells depends on caveolin, dynamin, and actin but not clathrin nor macropinocytosis pathways. The effects of overexpression and knockdown of caveolin-1, one components of the caveolae, was examined on EMCV infection. The results showed that EMCV infection was positive correlation with caveolin-1 expression. Confocal microscopy analysis and internalization assay showed that caveolin-1 is required at the early stage of EMCV infection.

Conclusions
Caveolin-1, dynamin, and actin-dependent endocytosis pathways are necessary for EMCV infection in vitro.