bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effectiveness of early versus delayed rehabilitation following rotator cuff repair: systematic review and meta-analyses
Authors: Mazuquin Bruno , Moffatt Maria , Gill Peter , Selfe James , Rees Jonathan , Drew Steve , Littlewood Chris 
Published: February 2021

ABSTRACTObjectiveTo investigate the effectiveness of early rehabilitation compared with delayed/standard rehabilitation after rotator cuff repair for pain, function, range of movement, strength, and repair integrity.DesignSystematic review and meta-analyses.MethodsWe searched databases and included randomised controlled trials (RCTs) comparing early with delayed/standard rehabilitation for patients undergoing rotator cuff repair surgery. We assessed risk of bias of the RCTs using the Cochrane RoB 2 tool.ResultsTwenty RCTs, with 1841 patients, were included. The majority of the RCTs were of high or unclear risk of overall bias. We found substantial variations in the rehabilitation programmes, time in the sling and timing of exercise progression. We found no statistically significant differences for pain and function at any follow-up except for the outcome measure Single Assessment Numeric Evaluation at six months (MD: 6.54; 95%CI: 2.24-10.84) in favour of early rehabilitation. We found statistically significant differences in favour of early rehabilitation for shoulder flexion at six weeks (MD: 7.36; 95%CI: 2.66-12.06), three (MD: 8.45; 95%CI: 3.43-13.47) and six months (MD: 3.57; 95%CI: 0.81-6.32) and one year (MD: 1.42; 95%CI: 0.21-2.64) and similar differences for other planes of movement. In terms of repair integrity at one year, regarding early mobilisation, the number needed to harm was 651.DiscussionCurrent approaches to early mobilisation, based largely on early introduction of passive movement, did not demonstrate significant differences in most clinical outcomes, although we found statistically significant differences in favour of early rehabilitation for range of movement. Importantly, there were no differences in repair integrity between early and delayed/standard rehabilitation. Most rehabilitation programmes did not consider early active movement as soon as the patient feels able. With ongoing variation in rehabilitation protocols there remains a need for large high quality RCT to inform the optimal approach to rehabilitation after rotator cuff repair surgery.
ACTIVE SURVEILLANCE OF THE SPUTNIK V VACCINE IN HEALTH WORKERS
Authors: Pagotto Vanina , Ferloni Analia , Soriano María Mercedes , Díaz Morena , Golde Manuel Braguisnky , González María Isabel , Asprea Valeria , Staneloni Inés , Vidal Gustavo , Silveira Martin , Zingoni Paula , Aliperti Valeria , Michelangelo Hernan , Figar Silvana 
Published: February 2021

AbstractIntroductionThe World Health Organization (WHO) recommends vaccination against Sars Cov-2 coronavirus to mitigate COVID-19 pandemic. On December 29th, the Argentine Ministry of Health started a vaccination plan with the Sputnik V vaccine emphasizing the registration of the Events Supposedly Attributed to Vaccines and Immunizations (ESAVI) in the National Surveillance System. The aim of this study is to determine the safety of this vaccine.MethodsIn an ongoing cohort study, health professionals from Hospital Italiano de Buenos Aires vaccinated with the first component of the Sputnik V vaccine (a rAd26 vector-based) were followed up. Safety at 72 hs was analysed from a self-report form. Local and systemic reactions were characterized as mild, moderate and severe. Incident rates were calculated per 1000 person-hours by age groups and gender. Adjusted hazard ratio and 95% Confidence Interval (HR; 95%CI) is obtained by Cox Regression Model.Results707 health professionals (mean age 35, 67% female) were vaccinated, response rate was 96,6% and 71,3% reported at least one ESAVI. Rate was 6.3 per 1.000 person-hours. Among local reactions, 54% reported pain at the injection site, 11% redness and swelling. Among systemic reactions 40% reported fever, 5% diarrhea and 68% new or worsened muscle pain. Five percent had serious adverse events that required medical evaluation and one inpatient.ESAVI rate was higher among females (65.4% vs 50%; HR 1.38, 95%CI 1.13-5.38) and in younger than 55 years-old (72.8% vs 32%; HR 2.66, 95%CI 1.32-1.68).ConclusionActive surveillance on safety for vaccines with emergency approval is mandatory. This study shows high rates of local and systemic reactions however early serious events were rare. Short term safety is supported by these preliminary findings. Studies on long term safety and efficacy, accoding sex and age, are needed.
Prophylactic post-operative high flow nasal oxygen versus conventional oxygen therapy in obese patients undergoing bariatric surgery (OXYBAR study): a pilot randomised controlled trial
Authors: Fulton Rachel , Millar Jonathan E , Merza Megan , Johnston Helen , Corley Amanda , Faulke Daniel , Rapchuk Ivan L , Tarpey Joe , Fanning Jonathon P , Lockie Philip , Lockie Shirley , Fraser John F 
Published: February 2021

SummaryObesity has become a global pandemic, as a result surgical intervention for weight loss has increased in popularity. Obese patients undergoing operative intervention pose several challenges in respect of their peri-operative care. A prominent feature is the alteration in respiratory mechanics and physiology evident in the obese. These combine to predispose individuals to a reduction in end expiratory lung volume (EELV) and atelectasis after anaesthesia. Consequently, the incidence of post-operative pulmonary complications (PPC) in this cohort has been reported to be in excess of 35%. High flow nasal oxygen (HFNO) has been suggested as a means of increasing EELV in post-operative patients, reducing the likelihood of PPC. We conducted a single centre, pilot, randomised controlled trial (RCT) of conventional oxygen therapy versus HFNO in patients after bariatric surgery. The aim of the study was to investigate the feasibility of using Electrical Impedance Tomography (EIT) as a means of assessing respiratory mechanics and to inform the design of larger, definitive RCT. Fifty patients were randomised during a 10-month period (conventional O2 n=25 vs. HFNO n = 25). One patient crossed over from conventional O2 to HFNO. There was no loss to follow-up. and analyses were performed on an intention-to-treat basis. Delta EELI was higher at 1 hour in patients receiving HFNO (mean difference = 831 Au (95% CI -1636 – 3298), p = 0.5). Continuous EIT beyond 1 hour was poorly tolerated. At 6 hours, there were no differences in PaO2/FiO2 ratio or PaCO2. ICU and hospital LOS were comparable. Only one patient developed a PPC (in the HFNO group). In a secondary analysis, delta EELI was positively correlated with increasing BMI. These data suggest that a large-scale randomised controlled trial of HFNO after bariatric surgery in an ‘all-comers’ population is likely infeasible. Furthermore, while EIT is a useful tool for assessing respiratory mechanics in this group it could not be considered a patient-centred outcome in a larger study. Similarly, the infrequency of PPC precludes its use as a primary outcome in a definitive trial. Future studies should focus on identifying patients most at risk for post-operative pulmonary complications and those in whom HFNO is likely to confer greatest benefit.
Machine learning to predict retention and viral suppression in South African HIV treatment cohorts
Authors: Maskew M , Sharpey-Schafer K , Voux L De , Bor J , Rennick M , Crompton T , Majuba P , Sanne I , Pisa PT , Miot J 
Published: February 2021

AbstractBackgroundTo optimize South Africa’s HIV response and reach PEPFAR’s 95:95:95 targets require same day initiations and patients successfully remaining on antiretroviral therapy, and remaining virally suppressed. Much effort and resources with HIV programmes have centred on tracking and tracing for those lost to follow-up (LTFU), through various back to care strategies to ensure retention of patients. However, programmes have noted the need for targeted, data driven and predictive approaches for identifying most at risk of patients for LTFU and viral unsuppression outcomes using available phenotypic data.MethodsWe applied predictive machine learning algorithms to anonymised, patient-level HIV programmatic data from two districts in South Africa, January 2016 - July 2019. We developed patient risk scores for two outcomes: 1) visit attendance within 28 days of next scheduled clinic visit and 2) suppression of next HIV viral load (VL). Demographic, clinical, behavioural (e.g. visit patterns) and laboratory data were investigated in multiple models as potential predictor variables of attending next scheduled visit and VL result at next visit.FindingsLongitudinal data was analysed using combinations of predictor features and classification algorithms. 445,636 Patients were included in the retention model and 363,977 in the VL model. Predictive accuracy, summarized by Area Under the Curve (AUC), ranged from 0.69 for attendance at next scheduled visit to 0.76 for VL suppression, suggesting the model correctly classified patients to whether a scheduled visit would be attended in 2 out of 3 patients and whether the VL result at next test would be suppressed in approximately 3 out of 4 patients. Key predictors for both retention & VL suppression include metrics on prior late or LTFU visits, the number of prior VL tests, the time since their last visit, the number of visits on their current regimen, the patients’ age, and their time on treatment. For retention, the number of visits at the current facility and the details of the next appointment date were also predictors. For VL suppression, other predictors included the range of thee previous VL value.ConclusionMachine learning can be used to identify HIV patients at risk for defaulting on treatment and not being virally suppressed. Predictive modelling can improve targeting of interventions through differentiated models of care, increasing cost-effectiveness and improving patient outcomes.
The SARS-CoV-2 transcriptome and the dynamics of the S gene furin cleavage site in primary human airway epithelia
Authors: Zou Wei , Xiong Min , Hao Siyuan , Zhang-Chen Elizabeth Yan , Baumlin Nathalie , Kim Michael D. , Salathe Matthias , Yan Ziying , Qiu Jianming 
Published: February 2021

AbstractThe novel severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) caused the devastating ongoing coronavirus disease-2019 (COVID-19) pandemic which poses a great threat to global public health. The spike (S) polypeptide of SARS-CoV-2 consists of the S1 and S2 subunits and is processed by cellular proteases at the S1/S2 boundary. The inclusion of the 4 amino acids (PRRA) at the S1/S2 boundary forms a furin cleavage site (FCS),682RRAR↓S686, distinguishing SARS-CoV-2 from its closest relative, the SARS-CoV. Various deletions surrounding the FCS have been identified in patients. When SARS-CoV-2 propagated in Vero cells, the virus acquired various deletions surrounding the FCS. In the present study, we studied the viral transcriptome in SARS-CoV-2 infected primary human airway epithelia (HAE) cultured at an air-liquid interface (ALI) with an emphasis on the viral genome stability at the S1/S2 boundary using RNA-seq. While we found overall the viral transcriptome is similar to that generated from infected Vero cells, we identified a high percentage of mutated viral genome and transcripts in HAE-ALI. Two highly frequent deletions were found at the S1/S2 boundary of the S gene: one is a deletion of 12 amino acids,678TNSPRRAR↓SVAS689, which contains the FCS, another is a deletion of 5 amino acids,675QTQTN679, which is two amino acids upstream of the FCS. Further studies on the dynamics of the FCS deletions in apically released virions revealed that the selective pressure for the FCS maintains the S gene stability in HAE-ALI but with exceptions, in which the FCS deletions are remained at a high rate. Thus, our study presents evidence for the role of unique properties of human airway epithelia in the dynamics of the FCS region during infection of human airways, which is donor-dependent.
Low doses of the organic insecticide spinosad trigger lysosomal defects, ROS driven lipid dysregulation and neurodegeneration in flies
Authors: Martelli Felipe , Zhongyuan Zuo , Wang Julia , Wong Ching-On , Karagas Nicholas E. , Roessner Ute , Rupasinghe Thusitha , Venkatachalam Kartik , Perry Trent , Batterham Philip , Bellen Hugo J. 
Published: February 2021

AbstractThe plight of insect populations around the world and the threats it poses to agriculture and ecosystems has thrown insecticide use into the spotlight. Spinosad is an organic insecticide, considered less harmful to beneficial insects than synthetic insecticides, but its mode of action remains unclear. Using Drosophila, we show that low doses of spinosad reduce cholinergic response in neurons by antagonizing Dα6 nAChRs. Dα6 nAChRs are transported to lysosomes that become enlarged and accumulate upon spinosad treatment. Oxidative stress is initiated in the central nervous system, and spreads to midgut and disturbs lipid storage in metabolic tissues in a Dα6-dependent manner. Spinosad toxicity was ameliorated with the antioxidant N-Acetylcysteine amide (NACA). Chronic exposures lead to mitochondrial defects, severe neurodegeneration and blindness in adult animals. The many deleterious effects of low doses of this insecticide reported here point to an urgent need for rigorous investigation of its impacts on beneficial insects.
Conserved Cdk inhibitors show unique structural responses to tyrosine phosphorylation
Authors: Swadling Jacob B. , Warnecke Tobias , Morris Kyle L. , Barr Alexis R. 
Published: February 2021

AbstractBalanced proliferation-quiescence decisions are vital during normal development and in tissue homeostasis and their dysregulation underlies tumorigenesis. Entry into proliferative cycles is driven by Cyclin/Cyclin-dependent kinases (Cdks). Conserved Cdk inhibitors (CKIs), p21Cip1/Waf1, p27Kip1and p57Kip2, bind to Cyclin/Cdks and inhibit Cdk activity. p27 tyrosine phosphorylation, in response to mitogenic signalling, promotes activation of CyclinD/Cdk4 and CyclinA/Cdk2. Tyrosine phosphorylation is conserved in p21 and p57, although the number of sites differs. We use molecular dynamics simulations to compare the structural changes in Cyclin/Cdk/CKI trimers induced by single and multiple tyrosine phosphorylation in CKIs and their impact on CyclinD/Cdk4 and CyclinA/Cdk2 activity. Despite shared structural features, CKI binding induces distinct structural responses in Cyclin/Cdks and the predicted effects of CKI tyrosine phosphorylation on Cdk activity are not conserved across CKIs. Our analyses suggest how CKIs may have evolved to be sensitive to different inputs to give context-dependent control of Cdk activity.
Pharmacological rescue of the brain cortex phenotype ofTbx1mouse mutants: significance for 22q11.2 deletion syndrome
Authors: Favicchia Ilaria , Flore Gemma , Cioffi Sara , Lania Gabriella , Baldini Antonio , Illingworth Elizabeth 
Published: February 2021

ABSTRACTObjectivesTbx1mutant mice are a widely used model of 22q11.2 deletion syndrome (22q11.2DS) because they manifest a broad spectrum of physical and behavioral abnormalities that is similar to that found in 22q11.2DS patients. InTbx1mutants, brain abnormalities include changes in cortical cytoarchitecture, hypothesized to be caused by the precocious differentiation of cortical progenitors. The objectives of this research are to identify drugs that have efficacy against the brain phenotype, and through a phenotypic rescue approach, gain insights into the pathogenetic mechanisms underlyingTbx1haploinsufficiency.Experimental approachDisease modelTbx1heterozygous and homozygous embryos. We tested the ability of two FDA-approved drugs, the LSD1 inhibitor Tranylcypromine and Vitamin B12, to rescue theTbx1mutant cortical phenotype. Both drugs have proven efficacy against the cardiovascular phenotype, albeit at a much reduced level compared to the rescue achieved in the brain.Methodsin situhybridization and immunostaining of histological brain sections using a subset of molecular markers that label specific cortical regions or cell types. Appropriate quantification and statistical analysis of gene and protein expression were applied to identify cortical abnormalities and to determine the level of phenotypic rescue achieved.ResultsCortical abnormalities observed inTbx1mutant embryos were fully rescued by both drugs. Intriguingly, rescue was obtained with both drugs inTbx1homozygous mutants, indicating that they function through mechanisms that do not depend uponTbx1function. This was particularly surprising for Vitamin B12, which was identified through its ability to increaseTbx1gene expression.ConclusionsTo our knowledge, this is only the second example of drugs to be identified that ameliorate phenotypes caused by the mutation of a single gene from the 22q11.2 homologous region of the mouse genome. This one drug-one gene approach might be important because there is evidence that the brain phenotype in 22q11.2DS patients is multigenic in origin, unlike the physical phenotypes, which are overwhelmingly attributable toTbx1haploinsufficiency. Therefore, effective treatments will likely involve the use of multiple drugs that are targeted to the function of specific genes within the deleted region.
Increased abundance of nuclear HDAC4 impairs neuronal development and long-term memory
Authors: Main Patrick , Tan Wei Jun , Wheeler David , Fitzsimons Helen L 
Published: February 2021

AbstractDysregulation of the histone deacetylase HDAC4 is associated with both neurodevelopmental and neurodegenerative disorders, and a feature common to many of these disorders is impaired cognitive function. HDAC4 shuttles between the nucleus and cytoplasm in both vertebrates and invertebrates and alterations in the amounts of nuclear and/or cytoplasmic HDAC4 have been implicated in these diseases. InDrosophila, HDAC4 also plays a critical role in the regulation of memory however the mechanisms through which it acts are unknown. Nuclear and cytoplasmically-restricted HDAC4 mutants were expressed in theDrosophilabrain to investigate a mechanistic link between HDAC4 subcellular distribution, transcriptional changes and neuronal dysfunction. Deficits in mushroom body morphogenesis, eye development and long-term memory correlated with increased abundance of nuclear HDAC4 but were associated with minimal transcriptional changes. Although HDAC4 sequesters MEF2 into punctate foci within neuronal nuclei, no alteration in MEF2 activity was observed on overexpression ofHDAC4, and knockdown ofMEF2had no impact on long-term memory, indicating that HDAC4 is likely not acting through MEF2. Similarly, deletion of the MEF2 binding site also had no impact on HDAC4-induced impairments in eye development, however it did significantly reduce the mushroom body deficits, thus nuclear HDAC4 acts through MEF2 to disrupt mushroom body development. These data provide insight into the mechanisms through which dysregulation of HDAC4 subcellular distribution impairs neurological function and provides new avenues for further investigation.
Direct acetylation of the conserved threonine of an immune regulator by bacterial effectors activates RPM1-dependent immunity inArabidopsis
Authors: Choi Sera , Prokchorchik Maxim , Lee Hyeonjung , Gupta Ravi , Lee Yoonyoung , Cho Buhyeon , Kim Min-Sung , Kim Sun Tae , Sohn Kee Hoon 
Published: February 2021

AbstractPlant pathogenic bacteria deliver effectors into plant cells to suppress immunity and promote pathogen survival (Buttner, 2016; Deslandes and Rivas, 2012); however, these effectors can be recognised by plant disease resistance (R) proteins to activate innate immunity (Jones and Dangl, 2006; Spoel and Dong, 2012). The bacterial acetyltransferase effectors HopZ5 and AvrBsT trigger immunity inArabidopsis thalianagenotypes lackingSUPPRESSOR OF AVRBST-ELICITED RESISTANCE 1(SOBER1) (Choi et al., 2018; Jayaraman et al., 2017),. Using anArabidopsisaccession, Tscha-1, that naturally lacks functionalSOBER1but is unable to recognise HopZ5, we demonstrate thatRESISTANCE TO P. SYRINGAE PV MACULICOLA 1(RPM1) andRPM1-INTERACTING PROTEIN 4(RIN4) are indispensable for HopZ5- or AvrBsT-triggered immunity. Remarkably, T166 of RIN4, the phosphorylation of which is induced by AvrB and AvrRpm1, was directly acetylated by HopZ5 and AvrBsT. Furthermore, we demonstrate that acetylation of RIN4 T166 is required and sufficient for activation of HopZ5- or AvrBsT-triggered defence. Finally, we show that SOBER1 interferes with HopZ5- or AvrBsT-triggered immunity by deacetylating RIN4 T166. Our findings indicate that multiple pathogen effectors with distinct biochemical properties modify a single residue in a guardee protein and activate a plant NLR immune receptor. We have thus elucidated detailed molecular mechanisms underlying the activation and suppression of plant innate immunity triggered by bacterial acetyltransferases.
Future profitability and stock returns of innovative firms: a pitch
Authors: Bedford Anna , Vojvoda Kristina , Ma Le , Ma Nelson 
Published: February 2021

Purpose
This research letter outlines the “AFAANZ shark pitch 2020” research journey and reflects on the application of the pitch template to the authors’ research topic on innovation, future profitability and stock returns.

Design/methodology/approach
This study begins by outlining how the research started, followed by the choice of authors’ replication study. This study then outlines the authors’ interactions with the corresponding author of the original study and the journal editor. The authors also detail their personal journey of using the pitch template.

Findings
The pitch template facilitated the identification of a replication study that has significant impact in informing Australian policy decisions. It allowed the authors to succinctly articulate and refine their research ideas.

Originality/value
This research letter highlights authors’ mistakes in using the pitch template and what they learned from interacting with the original authors and journal editor.
Preserving transferable skills in the accounting curriculum during the COVID-19 pandemic
Authors: Ng Frederick , Harrison Julie 
Published: February 2021

Purpose
The purpose of this paper is to provide a first-hand, critical reflection on the rapid redesign of a New Zealand university accounting course in response to the COVID-19 pandemic. The authors reflect on their experience of redesigning a course for online delivery, while preserving its focus on transferable skills.

Design/methodology/approach
This paper presents the authors’ commentary on and self-evaluation of the teaching of a final year accounting paper during the COVID-19 pandemic.

Findings
The authors provide lessons for developing transferable skills when pivoting to digital learning under extreme conditions. The authors found a multi-modal approach to course delivery that helped facilitate the development of transferable skills and self-reflection journals were particularly useful for motivating students in an online teaching environment. The authors also identified the efficacy of designing and evaluating online course delivery using a “transferable skills first” template to identify gaps in learning activities and assessments.

Originality/value
The pressures of rapidly pivoting to digital learning threatened the authors’ ability to maintain a focus on transferable skills. The authors provide a design method for maintaining and developing transferable skills in a digital environment using a “transferable-skills first” teaching philosophy.