bluuebunny/crossref_metadata_2025_split huggingface dataset:
Role of biomarkers and emerging technologies in defining and assessing neurobiological recovery after sport-related concussion: a systematic review
Authors: Tabor Jason B , Brett Benjamin L , Nelson Lindsay , Meier Timothy , Penner Linden C , Mayer Andrew R. , Echemendia Ruben J , McAllister Thomas , Meehan William P , Patricios Jon , Makdissi Michael , Bressan Silvia , Davis Gavin A , Premji Zahra , Schneider Kathryn J , Zetterberg Henrik , McCrea Michael 
Published: June 2023

ObjectiveDetermine the role of fluid-based biomarkers, advanced neuroimaging, genetic testing and emerging technologies in defining and assessing neurobiological recovery after sport-related concussion (SRC).DesignSystematic review.Data sourcesSearches of seven databases from 1 January 2001 through 24 March 2022 using keywords and index terms relevant to concussion, sports and neurobiological recovery. Separate reviews were conducted for studies involving neuroimaging, fluid biomarkers, genetic testing and emerging technologies. A standardised method and data extraction tool was used to document the study design, population, methodology and results. Reviewers also rated the risk of bias and quality of each study.Eligibility criteria for selecting studiesStudies were included if they: (1) were published in English; (2) represented original research; (3) involved human research; (4) pertained only to SRC; (5) included data involving neuroimaging (including electrophysiological testing), fluid biomarkers or genetic testing or other advanced technologies used to assess neurobiological recovery after SRC; (6) had a minimum of one data collection point within 6 months post-SRC; and (7) contained a minimum sample size of 10 participants.ResultsA total of 205 studies met inclusion criteria, including 81 neuroimaging, 50 fluid biomarkers, 5 genetic testing, 73 advanced technologies studies (4 studies overlapped two separate domains). Numerous studies have demonstrated the ability of neuroimaging and fluid-based biomarkers to detect the acute effects of concussion and to track neurobiological recovery after injury. Recent studies have also reported on the diagnostic and prognostic performance of emerging technologies in the assessment of SRC. In sum, the available evidence reinforces the theory that physiological recovery may persist beyond clinical recovery after SRC. The potential role of genetic testing remains unclear based on limited research.ConclusionsAdvanced neuroimaging, fluid-based biomarkers, genetic testing and emerging technologies are valuable research tools for the study of SRC, but there is not sufficient evidence to recommend their use in clinical practice.PROSPERO registration numberCRD42020164558.
Clinical recovery from concussion–return to school and sport: a systematic review and meta-analysis
Authors: Putukian Margot , Purcell Laura , Schneider Kathryn J , Black Amanda Marie , Burma Joel S , Chandran Avinash , Boltz Adrian , Master Christina L , Register-Mihalik Johna K , Anderson Vicki , Davis Gavin A , Fremont Pierre , Leddy John J , Maddocks David , Premji Zahra , Ronksley Paul E , Herring Stanley , Broglio Steven 
Published: June 2023

ObjectiveTo define the time frames, measures used and modifying factors influencing recovery, return to school/learn (RTL) and return to sport (RTS) after sport-related concussion (SRC).DesignSystematic review and meta-analysis.Data sources8 databases searched through 22 March 2022.Eligibility criteriaStudies with diagnosed/suspected SRC and interventions facilitating RTL/RTS or investigating the time and modifying factors for clinical recovery. Outcomes included days until symptom free, days until RTL and days until RTS. We documented study design, population, methodology and results. Risk of bias was evaluated using a modified Scottish Intercollegiate Guidelines Network tool.Results278 studies were included (80.6% cohort studies and 92.8% from North America). 7.9% were considered high-quality studies, while 23.0% were considered high risk of bias and inadmissible. The mean days until symptom free was 14.0 days (95% CI: 12.7, 15.4; I2=98.0%). The mean days until RTL was 8.3 (95% CI: 5.6, 11.1; I2=99.3%), with 93% of athletes having a full RTL by 10 days without new academic support. The mean days until RTS was 19.8 days (95% CI: 18.8, 20.7; I2=99.3%), with high heterogeneity between studies. Several measures define and track recovery, with initial symptom burden remaining the strongest predictor of longer days until RTS. Continuing to play and delayed access to healthcare providers were associated with longer recovery. Premorbid and postmorbid factors (eg, depression/anxiety, migraine history) may modify recovery time frames. Though point estimates suggest that female sex or younger age cohorts take longer to recover, the heterogeneity of study designs, outcomes and overlap in CIs with male sex or older age cohorts suggests that all have similar recovery patterns.ConclusionMost athletes have full RTL by 10 days but take twice as long for an RTS.PROSPERO registration numberCRD42020159928.
Targeted interventions and their effect on recovery in children, adolescents and adults who have sustained a sport-related concussion: a systematic review
Authors: Schneider Kathryn J , Critchley Meghan L , Anderson Vicki , Davis Gavin A , Debert Chantel T , Feddermann-Demont Nina , Gagnon Isabelle , Guskiewicz Kevin M , Hayden K Alix , Herring Stanley , Johnstone Corson , Makdissi Michael , Master Christina L , Moser Rosemarie Scolaro , Patricios Jon S , Register-Mihalik Johna K , Ronksley Paul E , Silverberg Noah D , Yeates Keith Owen 
Published: June 2023

ObjectivesWe evaluated interventions to facilitate recovery in children, adolescents and adults with a sport-related concussion (SRC).DesignSystematic review including risk of bias (modified Scottish Intercollegiate Guidelines Network tool).Data sourcesMEDLINE(R) and Epub Ahead of Print, In-Process & Other Non-Indexed Citations, Embase, APA PsycINFO, Cochrane Central Register of Controlled Trials, CINAHL Plus with Full Text, SPORTDiscus and Scopus searched until March 2022.Study eligibility criteria(1) Original research including randomised controlled trials (RCTs), quasi-experimental designs, cohort, comparative effectiveness studies; (2) focus on SRC; (3) English; (4) peer-reviewed and (5) evaluated treatment.Results6533 studies were screened, 154 full texts reviewed and 13 met inclusion (10 RCTs, 1 quasi-experimental and 2 cohort studies; 1 high-quality study, 7 acceptable and 5 at high risk of bias). Interventions, comparisons, timing and outcomes varied, precluding meta-analysis. For adolescents and adults with dizziness, neck pain and/or headaches >10 days following concussion, individualised cervicovestibular rehabilitation may decrease time to return to sport compared with rest followed by gradual exertion (HR 3.91 (95% CI 1.34 to 11.34)) and when compared with a subtherapeutic intervention (HR 2.91 (95% CI 1.01 to 8.43)). For adolescents with vestibular symptoms/impairments, vestibular rehabilitation may decrease time to medical clearance (vestibular rehab group 50.2 days (95% CI 39.9 to 60.4) compared with control 58.4 (95% CI 41.7 to 75.3) days). For adolescents with persisting symptoms >30 days, active rehabilitation and collaborative care may decrease symptoms.ConclusionsCervicovestibular rehabilitation is recommended for adolescents and adults with dizziness, neck pain and/or headaches for >10 days. Vestibular rehabilitation (for adolescents with dizziness/vestibular impairments >5 days) and active rehabilitation and/or collaborative care (for adolescents with persisting symptoms >30 days) may be of benefit.
When should an athlete retire or discontinue participating in contact or collision sports following sport-related concussion? A systematic review
Authors: Makdissi Michael , Critchley Meghan L , Cantu Robert C , Caron Jeffrey G , Davis Gavin A , Echemendia Ruben J , Fremont Pierre , Hayden K Alix , Herring Stanley A , Hinds Sidney R , Jordan Barry , Kemp Simon , McNamee Michael , Maddocks David , Nagahiro Shinji , Patricios Jon , Putukian Margot , Turner Michael , Sick Stacy , Schneider Kathryn J 
Published: June 2023

ObjectiveTo systematically review the scientific literature regarding factors to consider when providing advice or guidance to athletes about retirement from contact or collision sport following sport-related concussion (SRC), and to define contraindications to children/adolescent athletes entering or continuing with contact or collision sports after SRC.Data sourcesMedline, Embase, SPORTSDiscus, APA PsycINFO, CINAHL and Cochrane Central Register of Controlled Trials were searched systematically.Study eligibility criteriaStudies were included if they were (1) original research, (2) reported on SRC as the primary source of injury, (3) evaluated the history, clinical assessment and/or investigation of findings that may preclude participation in sport and (4) evaluated mood disturbance and/or neurocognitive deficits, evidence of structural brain injury or risk factors for increased risk of subsequent SRC or prolonged recovery.ResultsOf 4355 articles identified, 93 met the inclusion criteria. None of the included articles directly examined retirement and/or discontinuation from contact or collision sport. Included studies examined factors associated with increased risk of recurrent SRC or prolonged recovery following SRC. In general, these were low-quality cohort studies with heterogeneous results and moderate risk of bias. Higher number and/or severity of symptoms at presentation, sleep disturbance and symptom reproduction with Vestibular Ocular Motor Screen testing were associated with prolonged recovery and history of previous concussion was associated with a risk of further SRC.ConclusionNo evidence was identified to support the inclusion of any patient-specific, injury-specific or other factors (eg, imaging findings) as absolute indications for retirement or discontinued participation in contact or collision sport following SRC.PROSPERO registration numberCRD42022155121.
Examining later-in-life health risks associated with sport-related concussion and repetitive head impacts: a systematic review of case-control and cohort studies
Authors: Iverson Grant L , Castellani Rudolph J , Cassidy J David , Schneider Geoff M , Schneider Kathryn J , Echemendia Ruben J , Bailes Julian E , Hayden K Alix , Koerte Inga K , Manley Geoffrey T , McNamee Michael , Patricios Jon S , Tator Charles H , Cantu Robert C , Dvorak Jiri 
Published: June 2023

ObjectiveConcern exists about possible problems with later-in-life brain health, such as cognitive impairment, mental health problems and neurological diseases, in former athletes. We examined the future risk for adverse health effects associated with sport-related concussion, or exposure to repetitive head impacts, in former athletes.DesignSystematic review.Data sourcesSearch of MEDLINE, Embase, Cochrane, CINAHL Plus and SPORTDiscus in October 2019 and updated in March 2022.Eligibility criteriaStudies measuring future risk (cohort studies) or approximating that risk (case-control studies).ResultsTen studies of former amateur athletes and 18 studies of former professional athletes were included. No postmortem neuropathology studies or neuroimaging studies met criteria for inclusion. Depression was examined in five studies in former amateur athletes, none identifying an increased risk. Nine studies examined suicidality or suicide as a manner of death, and none found an association with increased risk. Some studies comparing professional athletes with the general population reported associations between sports participation and dementia or amyotrophic lateral sclerosis (ALS) as a cause of death. Most did not control for potential confounding factors (eg, genetic, demographic, health-related or environmental), were ecological in design and had high risk of bias.ConclusionEvidence does not support an increased risk of mental health or neurological diseases in former amateur athletes with exposure to repetitive head impacts. Some studies in former professional athletes suggest an increased risk of neurological disorders such as ALS and dementia; these findings need to be confirmed in higher quality studies with better control of confounding factors.PROSPERO registration numberCRD42022159486.
Faster, higher, stronger – together? A bibliometric analysis of author distribution in top medical education journals
Authors: Wondimagegn Dawit , Whitehead Cynthia Ruth , Cartmill Carrie , Rodrigues Eloy , Correia Antónia , Salessi Lins Tiago , Costa Manuel João 
Published: June 2023

IntroductionMedical education and medical education research are growing industries that have become increasingly globalised. Recognition of the colonial foundations of medical education has led to a growing focus on issues of equity, absence and marginalisation. One area of absence that has been underexplored is that of published voices from low-income and middle-income countries. We undertook a bibliometric analysis of five top medical education journals to determine which countries were absent and which countries were represented in prestigious first and last authorship positions.MethodsWeb of Science was searched for all articles and reviews published between 2012 and 2021 withinAcademic Medicine,Medical Education,Advances in Health Sciences Education,Medical Teacher, andBMC Medical Education. Country of origin was identified for first and last author of each publication, and the number of publications originating from each country was counted.ResultsOur analysis revealed a dominance of first and last authors from five countries: USA, Canada, UK, Netherlands and Australia. Authors from these five countries had first or last authored 70% of publications. Of the 195 countries in the world, 43% (approximately 83) were not represented by a single publication. There was an increase in the percentage of publications from outside of these five countries from 23% in 2012 to 40% in 2021.ConclusionThe dominance of wealthy nations within spaces that claim to be international is a finding that requires attention. We draw on analogies from modern Olympic sport and our own collaborative research process to show how academic publishing continues to be a colonised space that advantages those from wealthy and English-speaking countries.
The cigarette market in Brazil: new evidence on illicit practices from the 2019 National Health Survey
Authors: Szklo André Salem , Drope Jeffrey 
Published: June 2023

ObjectiveTo explore new evidence on illicit practices, such as selling legal brands below the minimum legal price (MLP), and smugglers selling illicit brands at or above the MLP.MethodsFor the first time in Brazil, self-reported information on cigarette brand name and price paid per pack in smokers’ last purchase from a nationally representative survey conducted in 2019 was used to distinguish the illicit and the legal markets. We estimated the proportion of illicit cigarette consumption, using the combination of brand and price.ResultsThe proportion of smuggled illicit cigarette consumption based on brands not approved on the Brazilian market was estimated at 38.6% (95% CI: 35.8% to 41.5%). When we added legal brands not paying taxes, it increased to 47.1% (95% CI: 44.2% to 49.9%). Around 25% of illicit brand cigarettes were sold at or above MLP.ConclusionsIn Brazil, since 2017 there is a lack of adjustment in tobacco taxes and the MLP for inflation and income growth. The increase in cigarette affordability and the presence on the market of a segment of ‘higher-priced’ illicit brands suggest patterns of illicit brand loyalty and/or perceived ‘brand quality’ among smokers of illicit cigarettes. The evidence also shows that a sizeable proportion of legal brand cigarettes were sold below the MLP. This study offers insight into what happened in circumstances in which a government failed to keep current with tax policies and the monitoring of domestic manufacturing. Brazil has been a world leader in the monitoring of the tobacco epidemic, and this study also offers an innovative use of data that an increasing number of countries are collecting.
Epidemiology of C2 fractures and determinants of surgical management: analysis of a national registry
Authors: Salottolo Kristin , Betancourt Alejandro , Banton Kaysie L , Acuna David , Panchal Ripul , Bar-Or David , Palacio Carlos H 
Published: June 2023

ObjectiveOperative management of axis fractures (C2) usually depend on the stability and location of the break and individual patient characteristics. We sought to describe the epidemiology of C2 fractures and hypothesized that determinants for surgery would differ by fracture diagnosis.MethodsPatients with C2 fractures were identified from the US National Trauma Data Bank from January 1, 2017, to January 1, 2020. Patients were classified by C2 fracture diagnosis: odontoid type II, odontoid types I and III, and non-odontoid fracture (hangman’s fracture or fractures through base of the axis). The primary comparison was C2 fracture surgery versus non-operative management. Multivariate logistic regression was used to identify independent associations with surgery. Decision tree-based models were developed to identify determinants for surgery.ResultsThere were 38 080 patients; 42.7% had an odontoid type II fracture; 16.5% had an odontoid type I/III fracture; and 40.8% had a non-odontoid fracture. All examined patient demographics, clinical characteristics, outcomes, and interventions differed by C2 fracture diagnosis. Overall, 5292 (13.9%) were surgically managed (17.5% odontoid type II, 11.0% odontoid type I/III, and 11.2% non-odontoid; p<0.001). The following covariates increased odds of surgery for all three fracture diagnoses: younger age, treatment at a level I trauma center, fracture displacement, cervical ligament sprain, and cervical subluxation. Determinants of surgery differed by fracture diagnosis: for odontoid type II, age ≤80 years, a displaced fracture, and cervical ligament sprain were determinants; for odontoid type I/III, age ≤85 years, a displaced fracture, and cervical subluxation were determinants; for non-odontoid fractures, cervical subluxation and cervical ligament sprain were the strongest determinants for surgery, by hierarchy.ConclusionsThis is the largest published study of C2 fractures and current surgical management in the USA. Odontoid fractures, regardless of type, had age and fracture displacement as the strongest determinants for surgical management, whereas associated injuries were determinants of surgery for non-odontoid fractures.Level of evidenceIII.
FDA Approval Summary: Tucatinib with Trastuzumab for Advanced Unresectable or Metastatic, Chemotherapy Refractory, HER2-Positive RAS Wild-Type Colorectal Cancer
Authors: Casak Sandra J. , Horiba M. Naomi , Yuan Mengdie , Cheng Joyce , Lemery Steven J. , Shen Yuan Li , Fu Wentao , Moore Jason N. , Li Yangbing , Bi Youwei , Auth Doris , Fesenko Nataliya , Kluetz Paul G. , Pazdur Richard , Fashoyin-Aje Lola A. 
Published: June 2023

Abstract
On January 19, 2023, the FDA granted accelerated approval to tucatinib in combination with trastuzumab for the treatment of patients with unresectable or metastatic RAS wild-type, HER2-positive colorectal cancer who have received prior treatment with fluoropyrimidine, oxaliplatin, and irinotecan. Approval was based on the pooled analysis of patients receiving tucatinib in combination with trastuzumab in MOUNTAINEER (NCT03043313), an open-label, multicenter trial. The primary endpoint was overall response rate (ORR) by RECIST 1.1 as per blinded central review committee (BIRC) assessment. The main secondary endpoint was duration of response (DOR) per BIRC assessment. Eighty-four eligible patients received the combination tucatinib and trastuzumab. With a median follow-up of 16 months, the ORR was 38% [95% confidence interval (CI): 28–49] and median DOR was 12.4 months (95% CI: 8.5–20.5); 81% of responders had a response lasting more than 6 months. The most common adverse reactions observed in at least 20% of patients receiving tucatinib in combination with trastuzumab were diarrhea, fatigue, rash, nausea, abdominal pain, infusion-related reactions, and fever. FDA concluded that the magnitude of ORR and durable responses observed in patients treated with tucatinib in combination with trastuzumab in the MOUNTAINEER trial are clinically meaningful, particularly in the context of a disease with estimated survival of 6–7 months with available therapy. This is the first approval for the subset of patients with HER2-positive colorectal cancer. This article summarizes the FDA's thought process and review of the data supporting this accelerated approval.
Cytokine-Mediated Degradation of the Transcription Factor ERG Impacts the Pulmonary Vascular Response to Systemic Inflammatory Challenge
Authors: Schafer Christopher M. , Martin-Almedina Silvia , Kurylowicz Katarzyna , Dufton Neil , Osuna-Almagro Lourdes , Wu Meng-Ling , Johnson Charmain F. , Shah Aarti V. , Haskard Dorian O. , Buxton Andrianna , Willis Erika , Wheeler Kate , Turner Sean , Chlebicz Magdalena , Scott Rizaldy P. , Kovats Susan , Cleuren Audrey , Birdsey Graeme M. , Randi Anna M. , Griffin Courtney T. 
Published: June 2023

BACKGROUND:
During infectious diseases, proinflammatory cytokines transiently destabilize interactions between adjacent vascular endothelial cells (ECs) to facilitate the passage of immune molecules and cells into tissues. However, in the lung, the resulting vascular hyperpermeability can lead to organ dysfunction. Previous work identified the transcription factor ERG (erythroblast transformation-specific–related gene) as a master regulator of endothelial homeostasis. Here we investigate whether the sensitivity of pulmonary blood vessels to cytokine-induced destabilization is due to organotypic mechanisms affecting the ability of endothelial ERG to protect lung ECs from inflammatory injury.

METHODS:

Cytokine-dependent ubiquitination and proteasomal degradation of ERG were analyzed in cultured HUVECs (human umbilical vein ECs). Systemic administration of TNFα (tumor necrosis factor alpha) or the bacterial cell wall component lipopolysaccharide was used to cause a widespread inflammatory challenge in mice; ERG protein levels were assessed by immunoprecipitation, immunoblot, and immunofluorescence. Murine
Erg
deletion was genetically induced in ECs (

Erg
fl/fl
;Cdh5[PAC]-Cre
ERT2

), and multiple organs were analyzed by histology, immunostaining, and electron microscopy.

RESULTS:

In vitro, TNFα promoted the ubiquitination and degradation of ERG in HUVECs, which was blocked by the proteasomal inhibitor MG132. In vivo, systemic administration of TNFα or lipopolysaccharide resulted in a rapid and substantial degradation of ERG within lung ECs but not ECs of the retina, heart, liver, or kidney. Pulmonary ERG was also downregulated in a murine model of influenza infection.

Erg
fl/fl
;Cdh5(PAC)-Cre
ERT2

mice spontaneously recapitulated aspects of inflammatory challenges, including lung-predominant vascular hyperpermeability, immune cell recruitment, and fibrosis. These phenotypes were associated with a lung-specific decrease in the expression of
Tek
—a gene target of ERG previously implicated in maintaining pulmonary vascular stability during inflammation.

CONCLUSIONS:
Collectively, our data highlight a unique role for ERG in pulmonary vascular function. We propose that cytokine-induced ERG degradation and subsequent transcriptional changes in lung ECs play critical roles in the destabilization of pulmonary blood vessels during infectious diseases.