bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Electronic Health Record as the Primary Data Source in a Pragmatic Trial: A Case Study
Authors: Russell Louise B. , Huang Qian , Lin Yuqing , Norton Laurie A. , Zhu Jingsan , Iannotte L. G. , Asch David A. , Mehta Shivan J. , Tanna Monique S. , Troxel Andrea B. , Volpp Kevin G. , Goldberg Lee R. 
Published: January 2022

Introduction. Pragmatic clinical trials test interventions in patients representative of real-world medical practice and reduce data collection costs by using data recorded in the electronic health record (EHR) during usual care. We describe our experience using the EHR to measure the primary outcome of a pragmatic trial, hospital readmissions, and important clinical covariates. Methods. The trial enrolled patients recently discharged from the hospital for treatment of heart failure to test whether automated daily monitoring integrated into the EHR could reduce readmissions. The study team used data from the EHR and several data systems that drew on the EHR, supplemented by the hospital admissions files of three states. Results. Almost three-quarters of enrollees’ readmissions over the 12-mo trial period were captured by the EHRs of the study hospitals. State data, which took 7 mo to more than 2 y from first contact to receipt of first data, provided the remaining one-quarter. Considerable expertise was required to resolve differences between the 2 data sources. Common covariates used in trial analyses, such as weight and body mass index during the index hospital stay, were available for >97% of enrollees from the EHR. Ejection fraction, obtained from echocardiograms, was available for only 47.6% of enrollees within the 6-mo window that would likely be expected in a traditional trial. Discussion. In this trial, patient characteristics and outcomes were collected from existing EHR systems, but, as usual for EHRs, they could not be standardized for date or method of measurement and required substantial time and expertise to collect and curate. Hospital admissions, the primary trial outcome, required additional effort to locate and use supplementary sources of data. Highlights Electronic health records are not a single system but a series of overlapping and legacy systems that require time and expertise to use efficiently. Commonly measured patient characteristics such as weight and body mass index are relatively easy to locate for most trial enrollees but less common characteristics, like ejection fraction, are not. Acquiring essential supplementary data—in this trial, state data on hospital admission—can be a lengthy and difficult process.
Secular Improvements in Cognitive Aging: Contribution of Education, Health, and Routine Activities
Authors: Beller Johannes , Kuhlmann Beatrice G. , Sperlich Stefanie , Geyer Siegfried 
Published: January 2022

Objectives Limited evidence exists regarding the reasons for secular changes in cognitive functioning over historical time. Thus, we examined potential explanatory factors for changes in cognitive speed, a central dimension of cognitive functioning. Methods Population-based data of middle-aged and older adults from Germany ( N = 5443) was used with baseline participants from 2002 to 2014, comparing the time periods 2002–2014. Results Cognitive speed improved in middle-aged adults (40–65) and older adults (66+). In both age groups, increases were partly explained by education, employment status, volunteering status, routine activities, and physical functioning. Changes in education were more important in explaining increases in older than in middle-aged adults, whereas changes in health were more important for explaining increases in middle-aged adults. Conclusions Cognitive speed increased in both age groups over historical time. Education, employment, volunteering, routine activities, and health were all important in explaining these changes, but their importance differed between age groups.
Medication Changes and Diagnosis of New Chronic Illnesses in COVID-19 Intensive Care Unit Survivors
Authors: Mohammad Rima A. , Nguyen Cynthia T. , Costello Patrick G. , Poyant Janelle O. , Yan Amy Yeung Siu , Landolf Kaitlin , Kim Andy , Artman Katherine L. , Taylor Dakota C. , Kenes Michael T. , Alkhateeb Tuqa , Stollings Joanna L. 
Published: January 2022

Background Currently, there is limited literature on the impact of the COVID-19 infection on medications and medical conditions in COVID-19 intensive care unit (ICU) survivors. Our study is, to our knowledge, the first multicenter study to describe the prevalence of new medical conditions and medication changes at hospital discharge in COVID-19 ICU survivors. Objective To determine the number of medical conditions and medications at hospital admission compared to at hospital discharge in COVID-19 ICU survivors. Methods Retrospective multicenter observational study (7 ICUs) evaluated new medical conditions and medication changes at hospital discharge in patients with COVID-19 infection admitted to an ICU between March 1, 2020, to March 1, 2021. Patient and hospital characteristics, baseline and hospital discharge medication and medical conditions, ICU and hospital length of stay, and Charlson comorbidity index were collected. Descriptive statistics were used to describe patient characteristics and number and type of medical conditions and medications. Paired t-test was used to compare number of medical conditions and medications from hospital discharge to admission. Results Of the 973 COVID-19 ICU survivors, 67.4% had at least one new medical condition and 88.2% had at least one medication change. Median number of medical conditions (increased from 3 to 4, P < .0001) and medications (increased from 5 to 8, P < .0001) increased from admission to discharge. Most common new medical conditions at discharge were pulmonary disorders, venous thromboembolism, psychiatric disorders, infection, and diabetes. Most common therapeutic categories associated with medication change were cardiology, gastroenterology, pain, hematology, and endocrinology. Conclusion and Relevance Our study found that the number of medical conditions and medications increased from hospital admission to discharge. Our results provide additional data to help guide providers on using targeted approaches to manage medications and diseases in COVID-19 ICU survivors after hospital discharge.
Canadian monitoring program of the surface contamination with 11 antineoplastic drugs in 122 centers
Authors: Delafoy Clémence , Roussy Claudine , Hudon Anny-France , Cirtiu Ciprian Mihai , Caron Nicolas , Bussières Jean-François , Tanguay Cynthia 
Published: January 2022

Introduction Occupational exposure to antineoplastic drugs can lead to long-term adverse effects on workers’ health. Environmental monitoring is conducted once a year, as part of a Canadian monitoring program. The objective was to describe contamination with 11 antineoplastic drugs measured on surfaces. Methods Six standardized sites in oncology pharmacy and six in outpatient clinic were sampled in each hospital. Samples were analyzed by ultra-performance liquid chromatography coupled with tandem mass spectrometry (non-platinum drugs) and by inductively coupled plasma mass spectrometry (platinum-based drugs). The limits of detection (in ng/cm2) were: 0.0006 for cyclophosphamide; 0.001 for docetaxel; 0.04 for 5-fluorouracil; 0.0004 for gemcitabine; 0.0007 for irinotecan; 0.0009 for methotrexate; 0.004 for paclitaxel, 0.009 for vinorelbine, 0.02 for doxorubicine, 0.0037 for etoposide and 0.004 for the platinum. Sub-analyses were done with a Kolmogorov-Smirnov test Results 122 Canadian hospitals participated. Cyclophosphamide (451/1412, 32% of positive samples, 90th percentile of concentration 0.0160 ng/cm2) and gemcitabine (320/1412, 23%, 0.0036 ng/cm2) were most frequently measured on surfaces. The surfaces most frequently contaminated with at least one drug were the front grille inside the biological safety cabinet (97/121, 80%) and the armrest of patient treatment chair (92/118, 78%).The distribution of cyclophosphamide concentration was higher for centers that prepared ≥ 5000 antineoplastic drug preparations/year (p < 0.0001). Conclusions This monitoring program allowed centers to benchmark their contamination with pragmatic contamination thresholds derived from the Canadian 90th percentiles. Problematic areas need corrective measures such as decontamination. The program helps to increase the workers’ awareness.
Does fear mediate the neuroticism-psychopathology link for adults living through the COVID-19 pandemic?
Authors: Lee Sherman A. , Jobe Mary C. 
Published: January 2022

Background COVID-19 has globally increased psychological distress. Although research has shown a clear link between neuroticism and psychopathology, pandemic fears—manifesting as fear of death and coronavirus anxiety, have not been examined as mediating factors for explaining this connection during the pandemic. Methods Therefore, to fill this void in the literature, this study examined 259 U.S. MTurk adult workers in May 2020 using an online questionnaire. The study used the Patient Health Questionnaire, the 8-item Big Five Inventory neuroticism subscale, a single-item fear of death measure, and the Coronavirus Anxiety Scale as well as collected demographic information to perform correlational and meditation analyses. Results The results showed that both coronavirus anxiety and fear of death partially mediated the relationship between neuroticism and symptoms of depression and generalized anxiety. The results also found that those high in trait neuroticism who were fearful of death or had coronavirus anxiety showed heightened levels of depression and general anxiety. Conclusion This study’s findings were consistent with previous research and current work on pandemic-related distress. In addition, the results of these findings can help bring to light the connectedness of these psychopathological constructs with fears surrounding the pandemic—which can be useful to both researchers and mental health professionals alike.
The COVID-19 experience of orthodontists in the UK
Authors: Sabbagh Yana , Lewis Benjamin RK , Chadwick Stephen M , Abu Alhaija Elham S 
Published: January 2022

Objective: To understand and compare the perceived impact and ongoing effects of the COVID-19 pandemic on orthodontic clinical services in the UK. Design: Descriptive cross-sectional survey. Setting: Online electronic questionnaire. Participants: Members of the British Orthodontic Society (BOS). Methods: Electronic questionnaires were circulated between March and June 2021. The UK survey was distributed via emails from the BOS, Orthodontic Managed Clinical Networks and WhatsApp groups. Results: A total of 560 unique responses were received. There were more respondents who were aged over 50 years (52%) then respondents who were aged below 50 years (48%) with the median age range being 50–54 years (20%). The main causes of disruption to clinical practice were felt to be national restrictions (85%), increased cross-infection measures (84%), social distancing (80%) and professional guidance (80%). Respondents felt more negatively in their opinions regarding dentistry’s preparedness for the pandemic (5%) and how dentistry coped in the crisis (35%), when compared to orthodontic services specifically (8% and 58%, respectively). The respondents were not confident about the potential beneficial effects of a vaccination programme on orthodontic clinical service provision (21%). Telephone consultations (84%) and video consultations (61%) were the main adaptations used by the respondents during the pandemic. Conclusions: Respondents felt that COVID-19 will have long-term societal, clinical and professional implications. The majority of our respondents supported the vaccination and weekly testing of the orthodontic team. Respondents felt that during the pandemic there had been a deterioration in care provision and were not optimistic about a vaccination programme restoring services to pre-pandemic levels of activity. During the pandemic, patients in active orthodontic treatment have been prioritised but at the expense of new and review patients, and as services recover respondents were concerned about the difficulty of arranging dental extractions.
Exploiting the Transformation Temperature to Reform an Infolded Nitinol Self-Expanding Peripheral Stent
Authors: Medranda Giorgio A. , Forrestal Brian J. , Case Brian C. , Waksman Ron , Bernardo Nelson L. 
Published: January 2022

Purpose: Nickel-titanium (nitinol) alloys possess a special set of properties that allow for a wide range of applications. Specifically, the transformation temperature for self-expanding nitinol peripheral stents allows for easy crimping at or below room temperature and reformation at body temperature becoming superelastic. Case Report: We report the case of an elderly man with iliac stenting 1 month prior, who presented several weeks after recovering from coronavirus disease 2019 with recurrent anterior-wall ST-elevation myocardial infarction. This was complicated by deformation and infolding of the previously implanted nitinol self-expanding stent in his right common iliac artery (CIA). Understanding nitinol’s specific properties, we proceeded with rapid injections of iced saline to cool the nitinol stent to its transformation temperature while nudging the distal end of the stent with a partially inflated balloon. This maneuver softened the nitinol stent, allowing us to “unfold” and reappose it against the wall of the right CIA, resulting in successful restoration of the original shape of the nitinol self-expanding stent. Conclusion: This represents the first reported case describing treatment of an infolded nitinol self-expanding peripheral stent by exploiting the transformation temperature of nitinol using iced cold saline to successfully restore the stent’s original shape and structure.
Optimal timing of anticoagulation after acute ischemic stroke with atrial fibrillation (OPTIMAS): Protocol for a randomized controlled trial
Authors: Best Jonathan G , Arram Liz , Ahmed Norin , Balogun Maryam , Bennett Kate , Bordea Ekaterina , Campos Marta G , Caverly Emilia , Chau Marisa , Cohen Hannah , Dehbi Hakim-Moulay , Doré Caroline J , Engelter Stefan T , Fenner Robert , Freemantle Nick , Hunter Rachael , James Martin , Lip Gregory YH , Murray Macey L , Norrving Bo , Sprigg Nikola , Veltkamp Roland , Zaczyk Iwona , Werring David J ,   the OPTIMAS investigators
Published: January 2022

Rationale Atrial fibrillation causes one-fifth of ischemic strokes, with a high risk of early recurrence. Although long-term anticoagulation is highly effective for stroke prevention in atrial fibrillation, initiation after stroke is usually delayed by concerns over intracranial hemorrhage risk. Direct oral anticoagulants offer a significantly lower risk of intracranial hemorrhage than other anticoagulants, potentially allowing earlier anticoagulation and prevention of recurrence, but the safety and efficacy of this approach has not been established. Aim Optimal timing of anticoagulation after acute ischemic stroke with atrial fibrillation (OPTIMAS) will investigate whether early treatment with a direct oral anticoagulant, within four days of stroke onset, is as effective or better than delayed initiation, 7 to 14 days from onset, in atrial fibrillation patients with acute ischemic stroke. Methods and design OPTIMAS is a multicenter randomized controlled trial with blinded outcome adjudication. Participants with acute ischemic stroke and atrial fibrillation eligible for anticoagulation with a direct oral anticoagulant are randomized 1:1 to early or delayed initiation. As of December 2021, 88 centers in the United Kingdom have opened. Study outcomes The primary outcome is a composite of recurrent stroke (ischemic stroke or symptomatic intracranial hemorrhage) and systemic arterial embolism within 90 days. Secondary outcomes include major bleeding, functional status, anticoagulant adherence, quality of life, health and social care resource use, and length of hospital stay. Sample size target A total of 3478 participants assuming event rates of 11.5% in the control arm and 8% in the intervention arm, 90% power and 5% alpha. We will follow a non-inferiority gatekeeper analysis approach with a non-inferiority margin of 2 percentage points. Discussion OPTIMAS aims to provide high-quality evidence on the safety and efficacy of early direct oral anticoagulant initiation after atrial fibrillation-associated ischemic stroke. Trial registrations: ISRCTN: 17896007; ClinicalTrials.gov: NCT03759938
The Most Dangerous Game: A Review of Head and Neck Injuries in American Football and Rugby
Authors: Richardson Jordan , Stanbouly Dani , Moynihan Harrison , Reynolds Renée M. , Recker Matthew J. , Markiewicz Michael R. 
Published: January 2022

Study Design The investigators designed and implemented a 20-year cross-sectional study using the National Electronic Injury Surveillance System database. Objective The purpose of this study is to estimate and compare hospital admission (danger) rates between rugby and football of those who presented to the emergency department with head and neck injuries after playing these sports. Methods The primary predictor variable was sport played. The primary outcome variable was danger, measured by hospital admission rates. Results Over the past 20 years, there has been a trend of decreasing incidence of injuries presenting to the emergency department in both sports. There was no difference in the rate of hospital admission when comparing football and rugby (OR, 1.2; P = .1). Male gender was associated with an increased risk of admission. Other variables associated with hospital admission included white racial group, injury taking place in the fall, being either young (15–24 years old) or senior (65 years of age and over), and being injured at school or at a sport/recreational facility. Conclusions There is no difference in danger as measured by admission rates between American football and rugby. There exists, however, several variables that are associated with admission when sustaining injury to the head and neck, when playing these two sports.
A Review of Strategies to Improve Biomechanical Fixation in the Cervical Spine
Authors: Oitment Colby , Thornley Patrick , Koziarz Frank , Jentzsch Thorsten , Bhanot Kunal 
Published: January 2022

Study Design Systematic review. Objectives Review the surgical techniques and construct options aimed at improving the biomechanical strength of cervical constructs. Methods A systematic review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A search of the MEDLINE, Embase, and Cochrane Library databases was performed to identify all studies examining biomechanical strategies utilized in the osteoporotic cervical spine. Screening was performed in duplicate for all stages of the review process. Results An initial search returned 3887 articles. After deletion of duplications and review of abstracts and full text, 39 articles met inclusion criteria. Overall, the surgical techniques reviewed aimed at obtaining rigid fixation in the setting of poor bone quality, or dispersing the forces at the bone-implant interface. We identified 6 key techniques to improve biomechanical fixation. These include bicortical fixation, appropriate screw selection (size and trajectory), PMMA augmentation, load sharing techniques, consideration of ancillary fixation around the occipitocervical junction, and supplementing the construct with post-operative collar or halo. Conclusion The summation of the literature highlights a framework of modalities available to surgeons to improve biomechanical fixation in the cervical spine. While these may improve construct strength in the setting of osteoporosis, there is a paucity of evidence available to make recommendations in this patient population.
Tcf1 is essential for initiation of oncogenic Notch1-driven chromatin topology in T-ALL
Authors: Antoszewski Mateusz , Fournier Nadine , Ruiz Buendía Gustavo A. , Lourenco Joao , Liu Yuanlong , Sugrue Tara , Dubey Christelle , Nkosi Marianne , Pritchard Colin E. J. , Huijbers Ivo J. , Segat Gabriela C. , Alonso-Moreno Sandra , Serracanta Elisabeth , Belver Laura , Ferrando Adolfo A. , Ciriello Giovanni , Weng Andrew P. , Koch Ute , Radtke Freddy 
Published: January 2022

Abstract
NOTCH1 is a well-established lineage specifier for T cells and among the most frequently mutated genes throughout all subclasses of T cell acute lymphoblastic leukemia (T-ALL). How oncogenic NOTCH1 signaling launches a leukemia-prone chromatin landscape during T-ALL initiation is unknown. Here we demonstrate an essential role for the high-mobility-group transcription factor Tcf1 in orchestrating chromatin accessibility and topology, allowing aberrant Notch1 signaling to convey its oncogenic function. Although essential, Tcf1 is not sufficient to initiate leukemia. The formation of a leukemia-prone epigenetic landscape at the distal Notch1-regulated Myc enhancer, which is fundamental to this disease, is Tcf1-dependent and occurs within the earliest progenitor stage even before cells adopt a T lymphocyte or leukemic fate. Moreover, we discovered a unique evolutionarily conserved Tcf1-regulated enhancer element in the distal Myc-enhancer, which is important for the transition of preleukemic cells to full-blown disease.
Location of eosinophils in the airway wall is critical for specific features of airway hyperresponsiveness and T2 inflammation in asthma
Authors: Al-Shaikhly Taha , Murphy Ryan C. , Parker Andrew , Lai Ying , Altman Matthew C. , Larmore Megan , Altemeier William A. , Frevert Charles W. , Debley Jason S. , Piliponsky Adrian M. , Ziegler Steven F. , Peters Michael C. , Hallstrand Teal S. 
Published: January 2022

BackgroundEosinophils are implicated as effector cells in asthma, but the functional implications of the precise location of eosinophils in the airway wall is poorly understood. We aimed to quantify eosinophils in the different compartments of the airway wall and associate these findings with clinical features of asthma and markers of airway inflammation.MethodsIn this cross-sectional study, we utilised design-based stereology to accurately partition the numerical density of eosinophils in both the epithelial compartment and the subepithelial space (airway wall area below the basal lamina including the submucosa) in individuals with and without asthma and related these findings to airway hyperresponsiveness (AHR) and features of airway inflammation.ResultsIntraepithelial eosinophils were linked to the presence of asthma and endogenous AHR, the type that is most specific for asthma. In contrast, both intraepithelial and subepithelial eosinophils were associated with type 2 (T2) inflammation, with the strongest association betweenIL5expression and intraepithelial eosinophils. Eosinophil infiltration of the airway wall was linked to a specific mast cell phenotype that has been described in asthma. We found that interleukin (IL)-33 and IL-5 additively increased cysteinyl leukotriene (CysLT) production by eosinophils and that the CysLT LTC4along with IL-33 increasedIL13expression in mast cells and altered their protease profile.ConclusionsWe conclude that intraepithelial eosinophils are associated with endogenous AHR and T2 inflammation and may interact with intraepithelial mast cellsviaCysLTs to regulate airway inflammation.