bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pediatric Non‐Alcoholic Fatty Liver Disease Is Affected by Genetic Variants Involved in Lifespan/Healthspan
Authors: Crudele Annalisa , Dato Serena , Re Oriana Lo , Maugeri Andrea , Sanna Paola , Giallongo Sebastiano , Oben Jude , Panera Nadia , De Rango Francesco , Mosca Antonella , Rose Giuseppina , Passarino Giuseppe , Alisi Anna , Vinciguerra Manlio 
Published: March 2021

ABSTRACTObjectives:Non‐alcoholic fatty liver disease (NAFLD) is the leading cause of chronic liver disease in both adults and children. Along with obesity and metabolic syndrome, genetic predisposition influences the progression of NAFLD. Here, we investigated the effect of lifespan/healthspan‐related single nucleotide polymorphisms (SNPs) on metabolically associated fatty liver disease in children.Methods:We evaluated the impact of 10 SNPs involved in both human liver/metabolic diseases and healthspan (interleukin‐6 [IL‐6] rs1800795, antisense non coding RNA in the INK4 locus (ANRIL) rs1556516, SH2B3/ATXN2 rs7137828, FURIN rs17514846, TP53 rs1042522, APOC3 rs2542052, KL rs9536314, KL rs9527025, SIRT6 rs107251, FOXO3 rs2802292) on NAFLD‐related metabolic and liver features in 177 pediatric patients with biopsy‐proven NAFLD, by comparing them to 146 healthy controls. We then applied a multidimensional reduction (MDR) case–control analysis of SNP–SNP interactions, to identify the joint effect of analyzed SNPs in predicting NAFLD and associated features.Results:Discrete SNPs were significantly associated with individual metabolic NAFLD features, but none of them significantly associated with NAFLD diagnosis. By testing potential synergies using the MDR approach, the best combination to diagnose NAFLD (P = 0.0011) resulted in the one encompassing IL‐6 rs1800795 and ANRIL rs1556516. Consistently, the risk combinations suggested by SNP–SNP analysis strongly associated with a higher level of fasting plasma blood glucose level (P = 0.024).Conclusion:In conclusion, here we demonstrated a synergic interaction between IL‐6 rs1800795 and ANRIL rs1556516 in the diagnosis of NAFLD, and NAFLD‐associated hyperglycemia in children. Larger studies are required to confirm our findings and to elucidate mechanisms by which the genetic interaction between these two genes influences healthspan in pediatric NAFLD.
Fixation Using Alternative Implants for the Treatment of Hip Fractures
Authors: Sprague Sheila , Bhandari Mohit , Bzovsky Sofia , Scott Taryn , Thabane Lehana , Heels-Ansdell Diane , O’Toole Robert V. , Howe Andrea , Gaski Greg E. , Hill Lauren C. , Brown Krista M. , Viskontas Darius , Zomar Mauri , Della Rocca Gregory J. , Slobogean Gerard P. 
Published: March 2021

Abstract

Objectives:
To conduct a pilot trial for the Fixation using Alternative Implants for the Treatment of Hip Fractures (FAITH-2) protocol to assess feasibility of a definitive trial.

Design:
Pilot trial.

Setting:
Twenty-five clinical sites across North America and Australia were initiated, but enrolment occurred in only 15 North American sites.

Patients/Participants:
Ninety-one randomized adults aged 18 to 60 years with a femoral neck fracture requiring surgical fixation.

Intervention:
Eligible patients were randomized to receive surgical treatment (sliding hip screw or cancellous screws) AND nutritional supplementation (4000 IU of vitamin D or placebo) for 6 months postfracture.

Main Outcome Measurements:
Feasibility outcomes included: clinical site initiation, participant enrolment rate, proportion of participants with complete 12-month follow-up, level of data quality, and rate of protocol adherence (number of randomization errors, crossovers between treatment groups, and daily supplementation adherence).

Results:
Eighty-six of 91 participants randomized into the pilot trial from 15 North American hospitals were deemed eligible. Four of five primary feasibility criteria were not achieved as we were unable to initiate clinical sites outside of North America and Australia due to feasibility constraints, slow participant enrolment (60 participants recruited over 36 mo), low adherence with daily nutritional supplementation at the 6-week (72.1%), 3-month (60.5%), and 6-month (54.7%) follow-up visits, and a high loss to follow-up rate of 22.1% at 12 months.

Conclusions:
Despite not meeting key feasibility criteria, we increased our knowledge on the logistics and anticipated barriers when conducting vitamin D supplementation trials in this trauma population, which can be used to inform the design and conduct of future trials on this topic.
Orthopaedic trauma care during a pandemic: initial responses in the United States and Canada
Authors: Swenning Todd , Coles Chad P. 
Published: March 2021

Abstract
As in other countries, COVID-19 had a significant impact on the delivery of Orthopaedic trauma care in North America. Both Canada and the United States had similar experiences and responses to the pandemic, while the burden of disease was significantly greater in the United States. There was significant uncertainty in the early phases of the pandemic, fueled by a lack of knowledge of the pathophysiology and spread of COVID-19, questions surrounding screening protocols, lack of guidelines for managing infected patients, and concern over limited supplies of personal protective equipment. As we gained knowledge and experience, changes were implemented to optimize the delivery of trauma care, some of which may have lasting effects. In this article, we share the experiences and lessons learned in Canada and the United States in response to the pandemic.
Orthopaedic trauma care during the COVID-19 Pandemic: the Latin American perspective
Authors: Padilla-Rojas Luis G. , López-Cervantes Roberto E. , López-Almejo Leonardo , Gutiérrez-Mendoza Israel , Amadei-Enghelmayer Rafael E. , Pesciallo César A. , Osma-Rueda José L. , Triana-Quijano Miguel A. , Santos-Silva Jorge Dos 
Published: March 2021

Abstract
At first glance, the COVID-19 pandemic and the field of orthopaedics and traumatology do not appear to be related. Although orthopaedists are not considered front-line personnel in the fight against the pandemic, the role of the surgeon as part of the overall health care team is crucial. The specialty of orthopaedics and orthopaedic trauma, due to its extraordinary scope, affects individuals of all ages and timely care affects patients’ long-term function and quality of life. Therefore, positioning the type and timing of care for musculoskeletal injuries and conditions, while maintaining the safety of the patient and healthcare providers, is essential. This article reviews the initial approaches to orthopaedic trauma care during the COVID-19 pandemic as established by 4 representative countries in Latin America: Mexico, Argentina, Colombia, and Brazil.
Orthopaedic trauma care: initial global approaches to management during a pandemic
Authors: Miclau Theodore 
Published: March 2021

Abstract
The coronavirus disease 2019 (COVID-19) has significantly affected the treatment of patients with surgical conditions, including those with acute and chronic musculoskeletal issues. While different global regions experienced different levels of COVID-19 activity and had different resources with which to deal with the pandemic, there were many consistent approaches to injury care and musculoskeletal trauma management. Understanding these approaches is necessary to improve current and future strategies to taking care of orthopaedic trauma patients in an infectious disease outbreak. This supplement focuses on approaches to musculoskeletal trauma care during the first months of the COVID-19 pandemic in 19 countries from 6 continents. This work represents a collaborative work of member societies of the International Orthopaedic Trauma Association (IOTA), an international association of orthopaedic societies dedicated to the promotion of musculoskeletal trauma care through advancements in patient care, research, and education. The information in these reports will aid efforts to understand and ultimately better address musculoskeletal trauma care worldwide during the first waves of the pandemic.
No-Charge Nonsurgical Facial Aesthetic Clinic in a Residency Program
Authors: Kaplan Jordan , Huyhn Anh , Izaddoost Shayan , Grome Luke , Reece Edward , Winocour Julian , Davis Matthew J. , Winocour Sebastian 
Published: March 2021

Background
In 2014, the Accreditation Council for Graduate Medical Education set minimum case requirements for injectable procedures as a surrogate for procedural competency. Despite the implementation of resident-run aesthetic surgery clinics, evidence suggests that many feel inadequately prepared as they go into practice even after meeting this requirement. To address this issue, our institution has implemented a separate resident clinic dedicated to neurotoxin and filler injections.

Objective
The authors discussed the logistics and benefits of how residents, faculty, clinic staff, and industry representatives together have created a no-cost, volunteer patient-based resident injectable clinic.

Description
Two half-day, no-cost clinics per week were established, with 1 clinic day coinciding with the chief resident aesthetic clinic. Designated staff coordinate patient visits and allocate specific rooms for this clinic. Industry representatives have provided injectable products at no cost through resident injectable education programs. Residents in postgraduation years 4 to 6 provide their own patients and perform procedures under direct faculty supervision. All encounters are documented in the electronic health record. To assess the utility of this clinic, a survey was sent to all recent graduates, some of whom participated in this program. Since its inception in May 2018, this injectable clinic has been running successfully with overwhelmingly positive feedback from all eligible residents who participated. To date, there have been no adverse events from these injections.

Conclusions
At our institution, the no-cost, volunteer patient-based resident injectable clinic has provided regular educational opportunities for plastic surgery residents to increase their experience with injectable procedures.
Unexpected, mystifying but simple three-dimensional dynamic fracture phenomena
Authors: Uenishi Koji 
Published: March 2021

This contribution addresses what can be learnt from our recent experimental observations of dynamic fracture development in brittle solid materials with real three-dimensional configurations. It is pointed out that the three-dimensional dynamic behaviour of (quasi-)brittle solids is essentially different not only from the one-dimensional dynamic one but also from the three-dimensional static one. The experimental observations include those of cylindrical concrete columns pressurized by deflagration at the centre and ice spheres subjected to dynamic impact at the bottom. Surprisingly, plain fracture patterns can be found through these experiments, but it does not seem simple to describe or predict the involved physical process by conventional analytical treatment or numerical simulations. Indeed, our understanding of mechanical details of actual three-dimensional fracture is still limited, especially in dynamic cases where the length scale of fracture and relevant waves is of the order of the size of solids under consideration. Although a more sophisticated physical interpretation including the dynamic interaction of waves in a relatively high-frequency range is required, the discussed dynamics of three-dimensional fracture development will assist in generating precisely controlled dynamic fracture networks that can be used for practical purposes of dismantling solid structural components and mitigating risks of catastrophic failures.
This article is part of the theme issue ‘Fracture dynamics of solid materials: from particles to the globe’.
Earthquake physics beyond the linear fracture mechanics: a discrete approach
Authors: Dȩbski W. , Klejment P. 
Published: March 2021

Fast development of seismology and related disciplines like seismic prospecting observed in recent decades has its roots in efficient applications of ideas of continuum media mechanics to describe seismic wave propagation through the Earth. Using the same approach enhanced by fracture mechanics methods to describe physical processes leading to nucleation, development and finally arresting of earthquake ruptures has also advanced our understanding of earthquake physics. However, in this case, we can talk only about a partial success since many aspects of earthquake processes are still very poorly understood if at all. We argue that to progress with seismic source analysis we need to turn our attention to a complementary approach, namely a ‘discrete’ one. We demonstrate here that taking into account discreteness of solid materials we are able not only to incorporate classical ‘continuum’ solutions but also reveal many details of fracture processes whose analysis is beyond the classical fracture mechanics. In this paper, we analyse tensional processes encountered in rock mechanics laboratory experiments, mining seismology and sometimes in realistic inter-plate seismic episodes. The ‘discreteness’ principle is implemented through the discrete element method—the numerical method entirely based on the discrete representation of the medium. Special attention is paid to energy accumulation and transformation during loading and relaxation phases of fragmentation processes.
This article is part of the theme issue ‘Fracture dynamics of solid materials: from particles to the globe’.
Early prediction of preeclampsia in pregnancy with circulating cell-free RNA
Authors: Moufarrej Mira N. , Vorperian Sevahn K. , Wong Ronald J. , Campos Ana A. , Quaintance Cecele C. , Sit Rene V. , Tan Michelle , Detweiler Angela M. , Mekonen Honey , Neff Norma F. , Druzin Maurice L. , Winn Virginia D. , Shaw Gary M. , Stevenson David K. , Quake Stephen R. 
Published: March 2021

AbstractLiquid biopsies that measure circulating cell-free RNA (cfRNA) offer an unprecedented opportunity to noninvasively study the development of pregnancy-related complications and to bridge gaps in clinical care. Here, we used 404 blood samples from 199 pregnant mothers to identify and validate cfRNA transcriptomic changes that are associated with preeclampsia (PE), a multi-organ syndrome which is the second largest cause of maternal death globally. We find that changes in cfRNA gene expression between normotensive (NT) and preeclamptic mothers are striking and stable early in gestation, well before the onset of symptoms. These changes are enriched for genes specific to neuromuscular, endothelial, and immune cell types and tissues that reflect important aspects of PE physiology and suggest new hypotheses for disease progression. This enabled identification and independent validation of a panel of 18 genes whose measurement between 5–16 weeks of gestation can form the basis of a liquid biopsy test that would identify mothers at risk of PE well before the clinical symptoms manifest themselves. Finally, we demonstrate that cfRNA changes reflect the multifactorial nature of PE and provide a means to non-invasively monitor maternal organ health. Tests based on these observations could help predict and manage who is at risk for PE, an important and until now unachieved objective for obstetric care.
COVID-19 Underreporting and its Impact on Vaccination Strategies
Authors: Albani Vinicius , Loria Jennifer , Massad Eduardo , Zubelli Jorge P. 
Published: March 2021

AbstractWe present a novel methodology for the stable rate estimation of hospitalization and death related to the Corona Virus Disease 2019 (COVID-19) using publicly available reports from various distinct communities. These rates are then used to estimate underreported infections on the corresponding areas by making use of reported daily hospitalizations and deaths. The impact of underreporting infections on vaccination strategies is estimated under different disease-transmission scenarios using a Susceptible-Exposed-Infective-Removed-like (SEIR) epidemiological model.One sentence SummaryUsing a novel methodology, we estimate COVID-19 underreporting from public data, quantifying its impact on vaccination.
Effective Connectivity and Dopaminergic Function of Fronto-Striato-Thalamic Circuitry in First-Episode Psychosis, Established Schizophrenia, and Healthy Controls
Authors: Sabaroedin Kristina , Razi Adeel , Chopra Sidhant , Tran Nancy , Pozaruk Andrii , Chen Zhaolin , Finlay Amy , Nelson Barnaby , Allott Kelly , Alvarez-Jimenez Mario , Graham Jessica , Baldwin Lara , Tahtalian Steven , Yuen Hok P , Harrigan Susy , Cropley Vanessa , Sharma Sujit , Saluja Bharat , Williams Robert , Pantelis Christos , Wood Stephen J. , O’Donoghue Brian , Francey Shona , McGorry Patrick , Aquino Kevin , Fornito Alex 
Published: March 2021

AbstractDysfunction of fronto-striato-thalamic (FST) circuits is thought to contribute to dopaminergic dysfunction and symptom onset in psychosis, but it remains unclear whether this dysfunction is driven by aberrant bottom-up subcortical signaling or impaired top-down cortical regulation. Here, we used spectral dynamic causal modelling (DCM) of resting-state functional magnetic resonance imaging (fMRI) to characterize the effective connectivity of dorsal and ventral FST circuits in a sample of 46 antipsychotic-naïve first-episode psychosis (FEP) patients and 23 controls and an independent sample of 36 patients with established schizophrenia (SCZ) patients and 100 controls. We found that midbrain and thalamic connectivity were implicated across both patient groups. Dysconnectivity in FEP patients was mainly restricted to the subcortex, with positive symptom severity being associated with midbrain connectivity. Dysconnectivity between the cortex and subcortical systems was only apparent in SCZ patients. In another independent sample of 33 healthy individuals who underwent concurrent fMRI and [18F]DOPA positron emission tomography, we found that striatal dopamine synthesis capacity was associated with the effective connectivity of nigrostriatal and striatothalamic pathways, implicating similar circuits as those associated with psychotic symptom severity in patients. Our findings thus indicate that subcortical dysconnectivity is salient in the early stages of psychosis, that cortical dysfunction may emerge later in the illness, and that nigrostriatal and striatothalamic signaling are closely related to striatal dopamine synthesis capacity, which is a robust risk marker for psychosis.
Determinants of losses in the latent tuberculosis infection cascade of care in Brazil: a prospective multicenter cohort study
Authors: Souza Alexandra Brito , B. Arriaga María , Amorim Gustavo , Araújo-Pereira Mariana , M. F. Nogueira Betânia , Queiroz Artur T. L. , Figueiredo Marina C. , Rocha Michael S. , Benjamin Aline , Moreira Adriana S. R. , de Oliveira Jamile G. , Rolla Valeria C. , Durovni Betina , Lapa e Silva José R. , Kritski Afrânio L. , Cavalcante Solange , Sterling Timothy R. , Andrade Bruno B. , Cordeiro-Santos Marcelo ,   for the RePORT Brazil consortium
Published: March 2021

ABSTRACTBackgroundFactors associated with losses in the latent tuberculosis infection (LTBI) cascade of care in contacts of tuberculosis (TB) patients were investigated in a multicenter prospective cohort from highly endemic regions in Brazil.MethodsClose contacts of 1,187 culture-confirmed pulmonary TB patients were prospectively studied between 2015 and 2019, with follow-up between 6 and 24 months. Data on TB screening by clinical investigation, radiographic examination and interferon-gamma release assay (IGRA) were collected. Stepwise multivariable models were used to identify determinants of losses in the LTBI cascade.ResultsAmong 4,145 TB contacts initially identified, 1,901 were examined (54% loss). Within those individuals, 933 were people living with HIV, ≤5 years-old and/or had positive IGRA results, therefore having recommendation to start TB preventive treatment (TPT). Of those, 454 (23%) initiated treatment, and 247 (6% of all TB contacts) completed TPT. Multivariable regression analysis revealed that living with HIV, illiteracy, and black/pardo (brown) race were independently associated with losses in cascade.ConclusionThere were losses at all LTBI cascade stages, but particularly at the initial screening and examination steps. Close contacts who are socially vulnerable and living with HIV were at heightened risk of not completing the LTBI cascade of care in Brazil.40-word summary of the article’s main pointWe investigated factors associated with losses in the latent tuberculosis infection cascade of care in a large cohort of contacts in Brazil. Social vulnerability and HIV infection were the most relevant determinants of losses in the LTBI cascade of care.
Outcome Reporting bias in Exercise Oncology trials (OREO): a cross-sectional study
Authors: Singh Benjamin , Fairman Ciaran M , Christensen Jesper F , Bolam Kate A , Twomey Rosie , Nunan David , Lahart Ian M 
Published: March 2021

AbstractBackgroundDespite evidence of selective outcome reporting across multiple disciplines, this has not yet been assessed in trials studying the effects of exercise in people with cancer. Therefore, the purpose of our study was to explore prospectively registered randomised controlled trials (RCTs) in exercise oncology for evidence of selective outcome reporting.MethodsEligible trials were RCTs that 1) investigated the effects of at least partially supervised exercise interventions in people with cancer; 2) were preregistered (i.e. registered before the first patient was recruited) on a clinical trials registry; and 3) reported results in a peer-reviewed published manuscript. We searched the PubMed database from the year of inception to September 2020 to identify eligible exercise oncology RCTs clinical trial registries. Eligible trial registrations and linked published manuscripts were compared to identify the proportion of sufficiently preregistered outcomes reported correctly in the manuscripts, and cases of outcome omission, switching, and silently introduction of non-novel outcomes.ResultsWe identified 31 eligible RCTs and 46 that were ineligible due to retrospective registration. Of the 405 total prespecified outcomes across the 31 eligible trials, only 6.2% were preregistered complete methodological detail. Only 16% (n=148/929) of outcomes reported in published results manuscripts were linked with sufficiently preregistered outcomes without outcome switching. We found 85 total cases of outcome switching. A high proportion (41%) of preregistered outcomes were omitted from the published results manuscripts, and many published outcomes (n=394; 42.4%) were novel outcomes that had been silently introduced (median, min-max=10, 0-50 per trial). We found no examples of preregistered efficacy outcomes that were measured, assessed, and analysed as planned.ConclusionsWe found evidence suggestive of widespread selective outcome reporting and non-reporting bias (outcome switching, omitted preregistered outcomes, and silently introduced novel outcomes). The existence of such reporting discrepancies has implications for the integrity and credibility of RCTs in exercise oncology.Preregistered protocolhttps://osf.io/dtkar/ (posted: November 19, 2019)