bluuebunny/crossref_metadata_2025_split huggingface dataset:
Epidemiology of Lower Leg Fractures at a Colorado Ski Resort
Authors: Hunt Kenneth J. , Cogburn Jennifer , Pierpoint Lauren , Kordell Jennifer R. , Saeedi Anahita , Spittler Jack , Khodaee Morteza 
Published: November 2022

Category: Trauma; Ankle; Sports Introduction/Purpose: Lower extremity fractures are relatively common among winter sports participants. The purpose of this study is to evaluate the demographics, injury mechanisms and environmental features among patients evaluated for lower leg fractures at a high-volume Colorado ski resort during five consecutive ski seasons. Methods: We conducted a retrospective descriptive analysis of patients with lower leg fractures at the Denver Health Winter Park Medical Center during the 2012/13 to 2016/17 ski seasons. We included all fractures below the knee (excluding tibial plateau and isolated fibular head fractures) sustained by skiing or snowboarding. Chart review was performed on the patient cohort, confirming diagnosis and evaluating factors associated with these fractures. Results: There were 346 lower leg, ankle, and/or foot fractures (5.4% of all clinic visits) during the study period. The average age was 33.1 years (range 4-74) with the majority being male (60.7%) and mainly as a result of skiing (84.7%). The majority of fractures were sustained among skiers and snowboarders who self-identified as beginner or intermediate skill level (64.8%), and on easy (green) or intermediate (blue) runs (64.9%). The most common fractures sustained were complete tibia-fibula fractures (30.9%) and lateral malleolus fractures (27.5%). More than half (57.0%) of complete tibia-fibula fractures were classified and boot top (mid- shaft just above the ski boot) fractures. The most common type of lateral malleolus fractures was Danis-Weber B (72.0%) with only 5.4% being Weber C fractures. Foot fractures were rare with only 12 total cases (3.5%). Conclusion: Skiers are much more likely to sustain lower leg fractures compared to snowboarders. Men were much more likely than women to sustain lower leg fractures. Most fractures occurred in mild or moderately difficult ski runs relative to advanced runs. Fractures appear to be more common with advancing age. Complete tibia-fibula fractures were the most common fractures sustained in all riders with lateral malleolus fractures being the second most common. Foot fractures are very rare in this population. Given the frequency of these injuries, additional education around prevention may be warranted.
Horizontal Cleavage Meniscus Tear Repaired Using a Cerclage Technique
Authors: MacLean Ian S. , Diduch David R. 
Published: November 2022

Background: Horizontal meniscal cleavage tears often occur in older individuals and have a degenerative component. Commonly, these are managed with partial meniscectomy. However, this results in significantly decreased contact area and increased peek contact forces. Arthroscopic repair has shown comparable results with repairs of other tear types. Indications: Cerclage repair is performed for a horizontal cleavage tear in individuals without significant arthritis and in whom partial meniscectomy would remove an unacceptably large portion of meniscal tissue. Technique Description: Using standard arthroscopy portals, a self-retrieving suture passing device is used to pass a #0 high-strength suture through the periphery of the meniscus. Arthroscopic knots are tied on the superior surface of the meniscus and pushed as far posteriorly as possible. A small 1-cm incision is made just through skin on the proximal, posteromedial border of the tibia. Through this a spinal needle is placed percutaneously to pass a Chia into the joint just posterior to the knot. A curved spinal needle from an outside-in meniscal repair kit may be used as this provides a better trajectory to tears closer to the root attachment. The Chia and suture limbs are retrieved out the front of the knee, and then the suture tails are shuttled out the back of the knee. This is repeated until the repair is complete. The suture limbs are then cut below skin. Results: After arthroscopic all-inside repair of horizontal cleavage tears, patients do well. Outcomes are similar to repairs of other meniscal tear types. In all, 80% of patients are satisfied with their results, and there is an 11% to 12% failure rate which is comparable to other types of tear repairs. Discussion: All-inside cerclage repair should be considered for individuals sustaining a horizontal cleavage tear. This preserves meniscal tissue compared to partial meniscectomy and yields good healing rates and outcomes. The author(s) attests that consent has been obtained from any patient(s) appearing in this publication. If the individual may be identifiable, the author(s) has included a statement of release or other written form of approval from the patient(s) with this submission for publication.
Low toxicity and excellent outcomes in patients with DLBCL without residual lymphoma at the time of CD19 CAR T-cell therapy
Authors: Wudhikarn Kitsada , Tomas Ana Alarcon , Flynn Jessica R. , Devlin Sean M. , Brower Jamie , Bachanova Veronika , Nastoupil Loretta J. , McGuirk Joseph P. , Maziarz Richard T. , Oluwole Olalekan O. , Schuster Stephen J. , Porter David L. , Bishop Michael R. , Riedell Peter A. , Perales Miguel-Angel 
Published: November 2022

Abstract
CD19 chimeric antigen receptor (CAR) T-cell therapy represents a breakthrough for patients with relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL), inducing sustained remissions in these patients. However, CAR T cells can result in significant toxicities. Preinfusion disease burden is associated with toxicities and outcomes after CAR T-cell therapy. We identified 33 patients with R/R DLBCL treated at 8 academic centers who had no detectable disease at the time of CAR T-cell therapy. The median time from leukapheresis to CAR T-cell infusion was 48 (19-193) days. Nine patients received axicabtagene ciloleucel, and 24 received tisagenlecleucel. There was no severe (grade ≥3) cytokine release syndrome, and only 1 patient developed severe neurotoxicity (grade 4). After a median follow-up of 16 months, 13 patients relapsed (39.4%) and 6 died (18.1%). One-year event-free survival and overall survival were 59.6% and 81.3%, respectively. Our findings suggest that, in patients with R/R DLBCL who have an indication for CAR T-cell therapy, treating patients in complete remission at the time of infusion is feasible, safe, and associated with favorable disease control. Further exploration in a larger clinical trial setting is warranted.
Respective roles of non-pharmaceutical interventions in bronchiolitis outbreaks: an interrupted time-series analysis based on a multinational surveillance system
Authors: Lenglart Lea , Ouldali Naim , Honeyford Kate , Bognar Zsolt , Bressan Silvia , Buonsenso Danilo , Da Dalt Liviana , De Tisham , Farrugia Ruth , Maconochie Ian K. , Moll Henriette A. , Oostenbrink Rianne , Parri Niccolo , Roland Damian , Rose Katy , Akyüz Özkan Esra , Angoulvant François , Aupiais Camille , Barber Clarissa , Barrett Michael , Basmaci Romain , Castanhinha Susana , Chiaretti Antonio , Durnin Sheena , Fitzpatrick Patrick , Fodor Laszlo , Gomez Borja , Greber-Platzer Susanne , Guedj Romain , Hey Florian , Jankauskaite Lina , Kohlfuerst Daniela , Mascarenhas Ines , Musolino Anna Maria , Pučuka Zanda , Reis Sofia , Rybak Alexis , Salamon Petra , Schaffert Matthias , Shahar-Nissan Keren , Supino Maria Chiara , Teksam Ozlem , Turan Caner , Velasco Roberto , Nijman Ruud G. , Titomanlio Luigi ,   the EPISODES Study Group
Published: November 2022

BackgroundBronchiolitis is a major source of morbimortality among young children worldwide. Non-pharmaceutical interventions (NPIs) implemented to reduce the spread of severe acute respiratory syndrome coronavirus 2 may have had an important impact on bronchiolitis outbreaks, as well as major societal consequences. Discriminating between their respective impacts would help define optimal public health strategies against bronchiolitis. We aimed to assess the respective impact of each NPI on bronchiolitis outbreaks in 14 European countries.MethodsWe conducted a quasi-experimental interrupted time-series analysis based on a multicentre international study. All children diagnosed with bronchiolitis presenting to the paediatric emergency department of one of 27 centres from January 2018 to March 2021 were included. We assessed the association between each NPI and change in the bronchiolitis trend over time by seasonally adjusted multivariable quasi-Poisson regression modelling.ResultsIn total, 42 916 children were included. We observed an overall cumulative 78% (95% CI −100– −54%; p<0.0001) reduction in bronchiolitis cases following NPI implementation. The decrease varied between countries from −97% (95% CI −100– −47%; p=0.0005) to −36% (95% CI −79–7%; p=0.105). Full lockdown (incidence rate ratio (IRR) 0.21 (95% CI 0.14–0.30); p<0.001), secondary school closure (IRR 0.33 (95% CI 0.20–0.52); p<0.0001), wearing a mask indoors (IRR 0.49 (95% CI 0.25–0.94); p=0.034) and teleworking (IRR 0.55 (95% CI 0.31–0.97); p=0.038) were independently associated with reducing bronchiolitis.ConclusionsSeveral NPIs were associated with a reduction of bronchiolitis outbreaks, including full lockdown, school closure, teleworking and facial masking. Some of these public health interventions may be considered to further reduce the global burden of bronchiolitis.
Single-cell RNA-seq uncovers cellular heterogeneity and provides a signature for paediatric sleep apnoea
Authors: Cortese Rene , Adams Taylor S. , Cataldo Kylie H. , Hummel Justin , Kaminski Naftali , Kheirandish-Gozal Leila , Gozal David 
Published: November 2022

BackgroundObstructive sleep apnoea (OSA) is a highly prevalent disease and a major cause of systemic inflammation leading to neurocognitive, behavioural, metabolic and cardiovascular dysfunction in children and adults. However, the impact of OSA on the heterogeneity of circulating immune cells remains to be determined.MethodsWe applied single-cell transcriptomics analysis (scRNA-seq) to identify OSA-induced changes in transcriptional landscape in peripheral blood mononuclear cell (PBMC) composition, which uncovered severity-dependent differences in several cell lineages. Furthermore, a machine-learning approach was used to combine scRNAs-seq cell-specific markers with those differentially expressed in OSA.ResultsscRNA-seq demonstrated OSA-induced heterogeneity in cellular composition and enabled the identification of previously undescribed cell types in PBMCs. We identified a molecular signature consisting of 32 genes, which distinguished OSA patients from various controls with high precision (area under the curve 0.96) and accuracy (93% positive predictive value and 95% negative predictive value) in an independent PBMC bulk RNA expression dataset.ConclusionOSA deregulates systemic immune function and displays a molecular signature that can be assessed in standard cellular RNA without the need for pre-analytical cell separation, thereby making the assay amenable to application in a molecular diagnostic setting.
Nontuberculous mycobacterial infections during cancer therapy with immune checkpoint inhibitors: a systematic review
Authors: Lombardi Andrea , Gramegna Andrea , Ori Margherita , Azzarà Cecilia , Blasi Francesco , Gori Andrea 
Published: November 2022

Immune checkpoint inhibitors (ICIs) are drugs growingly employed in the treatment of cancers, but there are still uncertainties about their possible role in the risk of developing nontuberculous mycobacteria (NTM) infections. To understand this, we performed a systematic review of the literature including studies published between 20 June 2012 and 20 June 2022 which described the occurrence of NTM infections among patients treated with ICIs. Overall, we included seven studies describing nine patients with NTM infection occurring during ICIs therapy.NTM infections occurring during ICIs therapy are mainly caused by germs belonging to theMycobacterium avium complex, involve primarily the lungs, on average 1 year after the start of treatment, and are not associated with immunosuppressive treatments.
AV-101, a novel inhaled dry-powder formulation of imatinib, in healthy adult participants: a phase 1 single and multiple ascending dose study
Authors: Gillies Hunter , Niven Ralph , Dake Benjamin T. , Chakinala Murali M. , Feldman Jeremy P. , Hill Nicholas S. , Hoeper Marius M. , Humbert Marc , McLaughlin Vallerie V. , Kankam Martin 
Published: November 2022

BackgroundOral imatinib has been shown to be effective, but poorly tolerated, in patients with advanced pulmonary arterial hypertension (PAH). To maintain efficacy while improving tolerability, AV-101, a dry powder inhaled formulation of imatinib, was developed to deliver imatinib directly to the lungs.MethodsThis phase 1, placebo-controlled, randomised single ascending dose (SAD) and multiple ascending dose (MAD) study evaluated the safety/tolerability and pharmacokinetics of AV-101 in healthy adults. The SAD study included five AV-101 cohorts (1 mg, 3 mg, 10 mg, 30 mg, 90 mg) and placebo, and a single-dose oral imatinib 400-mg cohort. The MAD study included three AV-101 cohorts (10 mg, 30 mg, 90 mg) and placebo; dosing occurred twice daily for 7 days.Results82 participants (SAD n=48, MAD n=34) were enrolled. For the SAD study, peak plasma concentrations of imatinib occurred within 3 h of dosing with lower systemic exposure compared to oral imatinib (p<0.001). For the MAD study, systemic exposure of imatinib was higher after multiple doses of AV-101 compared to a single dose, but steady-state plasma concentrations were lower for the highest AV-101 cohort (90 mg) compared to simulated steady-state oral imatinib at day 7 (p=0.0002). Across AV-101 MAD dose cohorts, the most common treatment-emergent adverse events were cough (n=7, 27%) and headache (n=4, 15%).ConclusionsAV-101 was well tolerated in healthy adults, and targeted doses of AV-101 significantly reduced the systemic exposure of imatinib compared with oral imatinib. An ongoing phase 2b/phase 3 study (IMPAHCT; clinicaltrials.gov identifierNCT05036135) will evaluate the safety/tolerability and clinical benefit of AV-101 for PAH.
Molecular assessment of mycobacterial burden in the treatment of nontuberculous mycobacterial disease
Authors: Ellis Huw C. , Moffatt Miriam F. , Churchward Colin , Cuthbertson Leah , Cookson William O.C. , Loebinger Michael R. 
Published: November 2022

IntroductionNontuberculous pulmonary disease causes significant morbidity and mortality. Efforts to tackle infections are hampered by the lack of reliable biomarkers for diagnosis, assessment and prognostication. The aim of this study was to develop molecular assays capable of identifying and quantifying multiple nontuberculous mycobacterial (NTM) species and to examine their utility in following individual patients’ clinical courses.MethodsDNA was extracted from 410 sputum samples obtained longitudinally from a cohort of 38 patients who were commencing treatment for eitherMycobacterium abscessusorMycobacterium aviumcomplex or who were patients with bronchiectasis who had never had positive cultures for mycobacteria. NTM quantification was performed with quantitative PCR assays developed in-house.ResultsThe molecular assays had highin vitrosensitivity and specificity for the detection and accurate quantification of NTM species. The assays successfully identified NTM DNA from human sputum samples (in vivosensitivity: 0.86–0.87%; specificity: 0.62–0.95%; area under the curve: 0.74–0.92). A notable association between NTM copy number and treatment (Friedman ANOVA (df)=22.8 (3), p≤0.01 forM. abscessustreatment group) was also demonstrated.ConclusionThe quantitative PCR assays developed in this study provide affordable, real-time and rapid measurement of NTM burden, with significant implications for prompt management decisions.
Association between metabolic syndrome and colorectal cancer incidence and all-cause mortality: a hospital-based observational study
Authors: Chung Kuan-Chih , Juang Sin-Ei , Chen Hong-Hwa , Cheng Kung-Chuan , Wu Kuen-Lin , Song Ling-Chiao , Lee Ko-Chao 
Published: November 2022

Abstract
Background
Metabolic syndrome (MetS) is a worldwide pandemic and complex disorder associated with colorectal cancer (CRC). This study aims to identify the influence of number of MetS components on CRC incidence and mortality, using a national, longitudinal dataset of hospital care in Taiwan.

Methods
Patient data from the Taiwan National Health Insurance Research Database (NHIRD) from 2001 to 2008 were extracted. Individuals with at least one inpatient diagnosis or 2 outpatient visits with any MetS component found within one year were identified and included. Subjects died within 12 months after the presence of MetS components or had any prior cancer were excluded. The study cohort were then divided into two groups: subjects who had more (i.e., 3 to 4) MetS components and those who had fewer (i.e., 1 to 2) MetS components. An 2:1 propensity score (PS) matching were performed to balance the baseline characteristics between the groups. Cox regression analyses were conducted to compare the CRC incidence and all-cause mortality at follow-up between subjects with more MetS components versus fewer components.

Results
After matching, a total of 119,843 subjects (78,274 with 1–2 and 41,569 with 3–4 MetS components) were analyzed. After adjusting for confounders, subjects with 3–4 MetS components had a significantly higher risk of CRC [adjusted hazard ratio (aHR), 1.28; 95% confidence interval (CI), 1.15–1.43, p < 0.001) and all-cause mortality (aHR, 1.13; 95% CI, 1.08–1.17, p < 0.001) than those with only 1–2 MetS components. In stratified analyses, the greatest increased risk of CRC incidence that 3–4 MetS components posed as compared to 1–2 MetS components was seen in subjects without CHD history (aHR, 1.41, 95% CI, 1.23–1.62, p < 0.001). In addition, 3–4 MetS components (vs. 1–2) led to greater all-cause mortality among the subjects < 65y, both genders, with or without CHD, subjects without CKD hisotry, both aspirin users and non-users, users of nonsteroidal anti-inflammatory drugs (NSAIDs), and users of statin.

Conclusion
Compared with 1–2 components, subjects with 3–4 MetS components are at greater risk of CRC and death at follow-up. This study also demonstrates the risks for CRC and all-cause mortality in certain subgroups of individuals with 3–4 MetS components compared to 1–2 components. These findings may help clinicians on the CRC risk stratification according to individuals’ characteristics, as well as to optimize the strategy of MetS surveillance and control in order to prevent CRC.
Professional and academic profile of the Brazilian research ethics committees
Authors: de Veras Santos Eugênio Pacelli , Guerriero Iara Coelho Zito 
Published: November 2022

Abstract
Background
Brazil is among the sixteen countries that conducts the most clinical trials in the world. It has a system to review research ethics with human beings made up by the National Commission on Research Ethics (CONEP) and 779 Research Ethics Committees (RECs), in 2017. The RECs are supposed to follow the same rules regarding their membership, although the RECs that review Social Science and Humanities (SSH) researches must respect Resolution 510/16. There are Brazilian RECs that review SSH and clinical trials. This study aimed to analyze the academic professional profile of the members of the CONEP and Brazilian RECs, their adequacy to the norms, and the challenges faced by the REC’s Chairs to compose their membership.

Methods
All 779 Brazilian RECs’ chairs are invited to fill in a questionnaire informing academic and professional background of the RECs members, and 92 answered. However, eight were excluded for having sent an incomplete questionnaire, leaving a total of 84 participants. The variables were described by absolute and relative frequency. The Chi-square test and ANOVA was used to analyze regional differences related difficulties to compose the committee. The significance level was 95%.

Results
The results showed a predominance of members from the biomedical area (57%), while 33% were members of the Social Sciences and Humanities and 5.5% were community representatives. As for the academic degree, there were (45.2%) PhD and (27.9%) masters. The divergences in relation to the guidelines result from the difficulties of having participants in some areas and the little interest in the work carried out by the committees.

Conclusion
The RECs are partially adequate to the norms and their performance may be compromised by the low participation of community representatives. The organization of REC’s specifics to review biomedical research could improve the ethical review process, ensuring a membership more qualified for these protocols.
Polish immigrants’ access to colorectal cancer screening in Norway – a qualitative study
Authors: Bhargava Sameer , Czapka Elżbieta , Hofvind Solveig , Kristiansen Maria , Diaz Esperanza , Berstad Paula 
Published: November 2022

AbstractBackgroundThe Norwegian colorectal cancer (CRC) screening programme started in May 2022. Inequities in uptake of CRC screening is a concern, and we expect that immigrants are at risk of non-uptake. Immigrants from Poland are the most populous immigrant group in Norway. The purpose of this study was to identify and explore factors that may facilitate Polish immigrants’ access to the Norwegian CRC screening programme.Material and methodsThis study was based on qualitative interviews with ten Polish immigrants in Norway. The participants represented a convenience sample that varied in terms of gender, education, employment, time in Norway, place of residence, Norwegian language skills and ties to the Norwegian-Polish community. We performed thematic content analysis to understand CRC screening from the perspective of Polish immigrants, using transnationalism and Levesque’s conceptualization of accessibility as theoretical frameworks.ResultsWe grouped our findings into three themes; “understanding of CRC development and the need to access health care”, “binationalism” and “improving accessibility through information”. Within these themes, various factors influenced the participants’ accessibility to CRC screening, namely knowledge about the screening and about causes, development and prevention of the disease, language, choice of screening country, trust in health personnel’s competence, information needs, methods and sources, as well as participants’ perception of the faecal immunochemical test screening user manual. These factors were further influenced by communication between the Polish community in Norway and Poland, as well as travel between the countries.ConclusionWe identified several factors that can be targeted with an aim to increase Polish immigrants’ access to the Norwegian CRC screening programme. Effective measures could include increasing cultural competence among health care providers and providing information in Polish through Polish-speaking health care professionals, general practitioners and internet portals used by the Polish-speaking community. Focusing on accessibility in a transnational setting, our findings may be of interest for policy makers and service providers planning preventive health measures for immigrants.