bluuebunny/crossref_metadata_2025_split huggingface dataset:
Zanubrutinib Versus Ibrutinib in Relapsed/Refractory Chronic Lymphocytic Leukemia and Small Lymphocytic Lymphoma: Interim Analysis of a Randomized Phase III Trial
Authors: Hillmen Peter , Eichhorst Barbara , Brown Jennifer R. , Lamanna Nicole , O'Brien Susan M. , Tam Constantine S. , Qiu Lugui , Kazmierczak Maciej , Zhou Keshu , Šimkovič Martin , Mayer Jiří , Gillespie-Twardy Amanda , Shadman Mazyar , Ferrajoli Alessandra , Ganly Peter S. , Weinkove Robert , Grosicki Sebastian , Mital Andrzej , Robak Tadeusz , Österborg Anders , Yimer Habte A. , Salmi Tommi , Ji Meng , Yecies Jessica , Idoine Adam , Wu Kenneth , Huang Jane , Jurczak Wojciech 
Published: November 2022

PURPOSE Zanubrutinib is a potent, irreversible next-generation Bruton tyrosine kinase (BTK) inhibitor designed to maximize BTK occupancy and minimize off-target kinase inhibition. We hypothesized that complete/sustained BTK occupancy may improve efficacy outcomes and increased BTK specificity may minimize off-target inhibition-related toxicities. PATIENTS AND METHODS ALPINE (ClinicalTrials.gov identifier: NCT03734016 ) is a global, randomized, open-label phase III study of zanubrutinib versus ibrutinib in patients with relapsed/refractory chronic lymphocytic leukemia. The primary end point was investigator-assessed overall response rate (ORR). The preplanned interim analysis was scheduled approximately 12 months after the first 415 patients were enrolled. RESULTS Between November 1, 2018, and December 14, 2020, 652 patients were enrolled. We present the interim analysis of the first 415 enrolled patients randomly assigned to receive zanubrutinib (n = 207) or ibrutinib (n = 208). At 15 months of median follow-up, ORR (partial or complete response) was significantly higher with zanubrutinib (78.3%; 95% CI, 72.0 to 83.7) versus ibrutinib (62.5%; 95% CI, 55.5 to 69.1; two-sided P < .001). ORR was higher with zanubrutinib versus ibrutinib in subgroups with del(17p)/ TP53 mutations (80.5% v 50.0%) and del(11q) (83.6% v 69.1%); 12-month progression-free survival in all patients was higher with zanubrutinib (94.9%) versus ibrutinib (84.0%; hazard ratio, 0.40; 95% CI, 0.23 to 0.69). Atrial fibrillation rate was significantly lower with zanubrutinib versus ibrutinib (2.5% v 10.1%; two-sided P = .001). Rates of cardiac events, major hemorrhages, and adverse events leading to treatment discontinuation/death were lower with zanubrutinib. CONCLUSION Zanubrutinib had a significantly higher ORR, lower atrial fibrillation rate, and improved progression-free survival and overall cardiac safety profile versus ibrutinib. These data support improved efficacy/safety outcomes with selective BTK inhibition.
Use of Machine Learning and Lay Care Coaches to Increase Advance Care Planning Conversations for Patients With Metastatic Cancer
Authors: Gensheimer Michael F. , Gupta Divya , Patel Manali I. , Fardeen Touran , Hildebrand Rachel , Teuteberg Winifred , Seevaratnam Briththa , Asuncion Mary Khay , Alves Nina , Rogers Brian , Hansen Jennifer , DeNofrio Jan , Shah Nigam H. , Parikh Divya , Neal Joel , Fan Alice C. , Moore Kaidi , Ruiz Shann , Li Connie , Khaki Ali Raza , Pagtama Judy , Chien Joanne , Brown Tiffany , Tisch Alison Holmes , Das Millie , Srinivas Sandhya , Roy Mohana , Wakelee Heather , Myall Nathaniel J. , Huang Jane , Shah Sumit , Lee Howard , Ramchandran Kavitha 
Published: November 2022

PURPOSE: Patients with metastatic cancer benefit from advance care planning (ACP) conversations. We aimed to improve ACP using a computer model to select high-risk patients, with shorter predicted survival, for conversations with providers and lay care coaches. Outcomes included ACP documentation frequency and end-of-life quality measures. METHODS: In this study of a quality improvement initiative, providers in four medical oncology clinics received Serious Illness Care Program training. Two clinics (thoracic/genitourinary) participated in an intervention, and two (cutaneous/sarcoma) served as controls. ACP conversations were documented in a centralized form in the electronic medical record. In the intervention, providers and care coaches received weekly e-mails highlighting upcoming clinic patients with < 2 year computer-predicted survival and no prior prognosis documentation. Care coaches contacted these patients for an ACP conversation (excluding prognosis). Providers were asked to discuss and document prognosis. RESULTS: In the four clinics, 4,968 clinic visits by 1,251 patients met inclusion criteria (metastatic cancer with no prognosis previously documented). In their first visit, 28% of patients were high-risk (< 2 year predicted survival). Preintervention, 3% of both intervention and control clinic patients had ACP documentation during a visit. By intervention end (February 2021), 35% of intervention clinic patients had ACP documentation compared with 3% of control clinic patients. Providers' prognosis documentation rate also increased in intervention clinics after the intervention (2%-27% in intervention clinics, P < .0001; 0%-1% in control clinics). End-of-life care intensity was similar in intervention versus control clinics, but patients with ≥ 1 provider ACP edit met fewer high-intensity care measures ( P = .04). CONCLUSION: Combining a computer prognosis model with care coaches increased ACP documentation.
How do reputation and conformity promote cooperation in the prisoner's dilemma?
Authors: Liu C. , Wang H. , Dai Y. 
Published: November 2022

Abstract
In evolutionary games, many mechanisms have been proposed to promote cooperation between individuals and the heterogeneity of these mechanisms has been widely investigated. However, the joint effects and heterogeneity of multiple mechanisms have not been adequately studied. Here, we introduce different neighborhoods and global tags to denote different reputation and conformity types, respectively, and discuss the joint effects and heterogeneity of reputation and conformity mechanisms on promoting cooperation in the prisoner's dilemma game. Simulation results show that the joint effects of reputation and conformity mechanisms can promote cooperation effectively and the heterogeneity of these two mechanisms promotes cooperation only in certain circumstances.
Low Skeletal Muscle Mass Accompanied by Abdominal Obesity Additively Increases the Risk of Incident Type 2 Diabetes
Authors: Jun Ji Eun , Lee Seung-Eun , Lee You-Bin , Kim Gyuri , Jin Sang-Man , Jee Jae Hwan , Kim Jae Hyeon 
Published: November 2022

AbstractContextLow skeletal muscle mass often accompanies abdominal obesity in the aging process.ObjectiveWe aimed to investigate the effect of reduced skeletal muscle mass and its interaction with abdominal obesity on incident type 2 diabetes.MethodsThis retrospective longitudinal study included 36 304 diabetes-free Koreans who underwent 2 or more health checkups annually or biannually. Appendicular skeletal muscle mass was measured by bioelectrical impedance analysis and was presented as a skeletal muscle mass index (SMI) adjusted for body weight. Presarcopenia was defined as an SMI less than 1 SD of the sex-specific mean for a healthy young reference group. Abdominal obesity was defined using waist circumference greater than or equal to 90 cm for men and greater than or equal to 85 cm for women. Participants were classified into 4 groups of normal, presarcopenia alone, abdominal obesity alone, and presarcopenic obesity according to initial body composition.ResultsThe cumulative incidence of diabetes was 9.1% during the 7-year follow-up. Compared with the highest tertile, the lowest sex-specific SMI tertile was significantly associated with a greater risk of incident type 2 diabetes (adjusted hazard ratio [HR] = 1.31; 95% CI, 1.18-1.45) in a fully adjusted model. Presarcopenic obesity significantly increased incident diabetes risk (adjusted HR = 1.57; 95% CI, 1.42-1.73) compared with normal body composition, presarcopenia alone, or abdominal obesity alone.ConclusionLow skeletal muscle mass and its coexistence with abdominal obesity additively increased the risk of incident type 2 diabetes independent of the glycometabolic parameters.
Clinical picture and treatment of myasthenia gravis in the adult population
Authors: Swatko Tomasz , Marzeda Magdalena , Blicharz Agnieszka , Małek Anna , Sygacz Oliwer 
Published: November 2022

Introduction and purpose: Myasthenia gravis (MG, myasthenia gravis ) is a classic example of an autoimmune disease caused by antibodies against acetylcholine receptors ( AChR) , muscle-specific kinase (MuSK) or other AChR-related proteins in the postsynaptic muscle membrane leading to characteristic muscle weakness.
Description of the state of knowledge: It is not fully known why the body begins to produce antibodies that act against its own acetylcholine receptors. The main role in producing these antibodies is played by the thymus gland, a gland located in the chest. The thymus gland is normally present in children, while it atrophies in adults. In about 60% of myasthenia gravis patients, however, it is present (we say they have a persistent thymus), and 15% of patients have a thymic neoplasm called a thymoma.
Summary: Myasthenia gravis is the most common neuromuscular junction disorder. Myasthenia gravis is a rare disease that involves muscle weakness of the eyes, pharynx, larynx, respiratory muscles and limbs. Clinical manifestations vary depending on the type of autoantibody and the presence of thymoma. The diagnosis of the disease should be confirmed by electrodiagnostic and laboratory tests in addition to the typical symptoms. Myasthenia gravis can manifest at any age, both in men ( peak incidence 50-60 years of age) and women ( peak incidence 20-30 years of age). Muscle fatigue intensifies after any exercise, even small ones. The patient feels best in the morning hours, right after waking up. As time passes, the symptoms of muscle fatigue intensify and the patient becomes less and less fit. For this reason, patients should rest frequently.
Wound fluid ceftriaxone concentrations after local application with calcium sulphate as carrier material in the treatment of orthopaedic device-associated hip infections
Authors: Wiesli Matthias G. , Livio Françoise , Achermann Yvonne , Gautier Emanuel , Wahl Peter 
Published: November 2022

Aims There is a considerable challenge in treating bone infections and orthopaedic device-associated infection (ODAI), partly due to impaired penetration of systemically administrated antibiotics at the site of infection. This may be circumvented by local drug administration. Knowledge of the release kinetics from any carrier material is essential for proper application. Ceftriaxone shows a particular constant release from calcium sulphate (CaSO4) in vitro, and is particularly effective against streptococci and a large portion of Gram-negative bacteria. We present the clinical release kinetics of ceftriaxone-loaded CaSO4 applied locally to treat ODAI. Methods A total of 30 operations with ceftriaxone-loaded CaSO4 had been performed in 28 patients. Ceftriaxone was applied as a single local antibiotic in 21 operations and combined with vancomycin in eight operations, and in an additional operation with vancomycin and amphotericin B. Sampling of wound fluid was performed from drains or aspirations. Ceftriaxone concentrations were measured by liquid chromatography with tandem mass spectrometry (LC-MS/MS). Results A total of 37 wound fluid concentrations from 16 operations performed in 14 patients were collected. The ceftriaxone concentrations remained approximately within a range of 100 to 200 mg/l up to three weeks. The median concentration was 108.9 mg/l (interquartile range 98.8 to 142.5) within the first ten days. No systemic adverse reactions were observed. Conclusion Our study highlights new clinical data of locally administered ceftriaxone with CaSO4 as carrier material. The near-constant release of ceftriaxone from CaSO4 observed in vitro could be confirmed in vivo. The concentrations remained below known local toxicity thresholds. Cite this article: Bone Joint Res 2022;11(11):835–842.
Diabetes medications and associations with Covid-19 outcomes in the N3C database: A national retrospective cohort study
Authors: Bramante Carolyn T. , Johnson Steven G. , Garcia Victor , Evans Michael D. , Harper Jeremy , Wilkins Kenneth J. , Huling Jared D. , Mehta Hemalkumar , Alexander Caleb , Tronieri Jena , Hong Stephenie , Kahkoska Anna , Alamgir Joy , Koraishy Farrukh , Hartman Katrina , Yang Kaifeng , Abrahamsen Trine , Stürmer Til , Buse John B. ,   N3C core authors
Published: November 2022

Background
While vaccination is the most important way to combat the SARS-CoV-2 pandemic, there may still be a need for early outpatient treatment that is safe, inexpensive, and currently widely available in parts of the world that do not have access to the vaccine. There are in-silico, in-vitro, and in-tissue data suggesting that metformin inhibits the viral life cycle, as well as observational data suggesting that metformin use before infection with SARS-CoV2 is associated with less severe COVID-19. Previous observational analyses from single-center cohorts have been limited by size.

Methods
Conducted a retrospective cohort analysis in adults with type 2 diabetes (T2DM) for associations between metformin use and COVID-19 outcomes with an active comparator design of prevalent users of therapeutically equivalent diabetes monotherapy: metformin versus dipeptidyl-peptidase-4-inhibitors (DPP4i) and sulfonylureas (SU). This took place in the National COVID Cohort Collaborative (N3C) longitudinal U.S. cohort of adults with +SARS-CoV-2 result between January 1 2020 to June 1 2021. Findings included hospitalization or ventilation or mortality from COVID-19. Back pain was assessed as a negative control outcome.

Results
6,626 adults with T2DM and +SARS-CoV-2 from 36 sites. Mean age was 60.7 +/- 12.0 years; 48.7% male; 56.7% White, 21.9% Black, 3.5% Asian, and 16.7% Latinx. Mean BMI was 34.1 +/- 7.8kg/m2. Overall 14.5% of the sample was hospitalized; 1.5% received mechanical ventilation; and 1.8% died. In adjusted outcomes, compared to DPP4i, metformin had non-significant associations with reduced need for ventilation (RR 0.68, 0.32–1.44), and mortality (RR 0.82, 0.41–1.64). Compared to SU, metformin was associated with a lower risk of ventilation (RR 0.5, 95% CI 0.28–0.98, p = 0.044) and mortality (RR 0.56, 95%CI 0.33–0.97, p = 0.037). There was no difference in unadjusted or adjusted results of the negative control.

Conclusions
There were clinically significant associations between metformin use and less severe COVID-19 compared to SU, but not compared to DPP4i. New-user studies and randomized trials are needed to assess early outpatient treatment and post-exposure prophylaxis with therapeutics that are safe in adults, children, pregnancy and available worldwide.
Incidence of HIV infection and associated factors among female sex workers in Côte d’Ivoire, results of the ANRS 12361 PrEP-CI study using recent infection assays
Authors: Nouaman Marcellin N. , Becquet Valentine , Plazy Mélanie , Coffie Patrick A. , Zébago Clémence , Montoyo Alice , Anoma Camille , Eholié Serge , Dabis François , Larmarange Joseph ,   for the ANRS 12361 PrEP-CI Study group
Published: November 2022

Background
This study aimed to estimate, using an HIV Recent Infection Testing Algorithm (RITA), the HIV incidence and its associated factors among female sex workers (FSW) in Côte d’Ivoire.

Methods
A cross-sectional study was conducted in 2016–2017 in Abidjan and San Pedro’s region among FSW aged ≥ 18 years. In addition, a sociodemographic questionnaire, HIV screening was carried out by two rapid tests. In the event of a positive result, a dried blood spot sample was taken to determine, using a RITA adapted to the Ivorian context, if it was a recent HIV infection.

Results
A total of 1000 FSW were surveyed with a median age of 25 years (interquartile range: 21–29 years). 39 (3.9%) tested positive for HIV. The incidence of HIV was estimated to be 2.3 per 100 person-years, with higher incidence rates among those 24 years old or less (3.0% vs. 1.9%), non-Ivorian FSW (3.2% vs. 1.9%) and those with the lowest education level (4.6% in FSW who never went to school vs. 2.6%). The incidence seemed to be associated with the sex work practice conditions: higher incidence among FSW whose usual price was less than 3.50$ (4.3% vs.1.0%), FSW who had a larger number of clients on the last day of work (6.1% in those with 7 clients or more vs. 1.8%), FSW who reported not always using condoms with their clients (8.5% vs. 1.5%) and FSW who reported agreeing to sex without a condom in exchange for a large sum of money (10.1% vs. 1.2%).

Conclusion
This study confirms that FSW remain highly exposed to HIV infection. Exposure to HIV is also clearly associated with certain sex-work factors and the material conditions of sex work. Efforts in the fight against HIV infection must be intensified to reduce new infections among FSW.
Starting the SToP trial: Lessons from a collaborative recruitment approach
Authors: McRae Tracy , Walker Roz , Jacky John , Katzenellenbogen Judith M. , Coffin Juli , Christophers Ray , Carapetis Jonathan , Bowen Asha C. 
Published: November 2022

Objective
Recruitment in research can be challenging in Australian Aboriginal contexts. We aimed to evaluate the SToP (See, Treat, Prevent skin infections) trial recruitment approach for Aboriginal families to identify barriers and facilitators and understand the utility of the visual resource used.

Methods
This qualitative participatory action research used purposive sampling to conduct six semi-structured interviews with staff and five yarning sessions with Aboriginal community members from the nine communities involved in the SToP trial that were audio recorded and transcribed verbatim before thematic analysis.

Findings
Community members valued the employment of local Aboriginal facilitators who used the flipchart to clearly explain the importance of healthy skin and the rationale for the SToP trial while conducting recruitment. A prolonged process, under-developed administrative systems and stigma of the research topic emerged as barriers.

Conclusion
Partnering with a local Aboriginal organisation, employing Aboriginal researchers, and utilising flip charts for recruitment was seen by some as successful. Strengthening governance with more planning and support for recordkeeping emerged as future success factors.

Implications for public health
Our findings validate the importance of partnership for this critical phase of a research project. Recruitment strategies should be co-designed with Aboriginal research partners. Further, recruitment rates for the SToP trial provide a firm foundation for building partnerships between organisations and ensuring Aboriginal perspectives determine recruitment methods.
A focused multi-state model to estimate the pediatric and adolescent HIV epidemic in Thailand, 2005–2025
Authors: Desmonde Sophie , Lolekha Rangsima , Costantini Sydney , Siraprapasiri Taweesap , Frank Simone , Bakkali Taoufik , Benjarattanaporn Patchara , Hou Taige , Jantaramanee Supiya , Kuttiparambil Beena , Sethaputra Chuenkamol , Ross Jeremy , Ciaranello Andrea 
Published: November 2022

Background
We estimated the magnitude of the HIV epidemic among children and youth living with HIV (CYHIV) aged 0–25 years in Thailand, projecting forward from 2005 to 2025, and identified underreported input parameters that influence epidemic projections, in order to inform future public health and research priorities.

Methods
We developed a focused multi-state transition model incorporating perinatally-acquired HIV and non-perinatally-acquired HIV, stratified by population, including men who have sex with men (MSM), female sex workers (FSW), people who inject drugs (PWID), and the remainder of the population (“other”). We populated the model with published and programmatic data from the Thai national AIDS program when available. We projected the period from 2005–2025 and compared model results to programmatic data and projections from other models. In a scenario analysis, we projected the potential impact of pre-exposure prophylaxis (PrEP) for MSM from 2018–2025.

Results
The initial 2005 cohort was comprised of 66,900 CYHIV; 8% CYHIV were <5 years, 21% were 5–14 years, and 71% were 15–25 years of age. By 2020, 94% were projected to be >15 years and infections among MSM constituted 83% of all new HIV infections. The numbers of CYHIV decreased over time, projected to reach 30,760 by 2020 (-54%) and 22,640 by 2025 (-66%). The proportion of all CYHIV aged 0–25 who were diagnosed and on ART increased from 37 to 60% over the 2005–2025 period. Projections were sensitive to variations in assumptions about initial HIV prevalence and incidence among MSM, PWID, and “other” youth.

Conclusions
More data on incidence rates among sexual and gender minority youth and PWID are needed to characterize the role of specific exposures and key populations in the adolescent HIV epidemic. More accurate estimates will project shifts in population and inform more targeted interventions to prevent and care for Thai CYHIV.
Recognition of knowledge translation practice in Canadian health sciences tenure and promotion: A content analysis of institutional policy documents
Authors: Sibley Kathryn M. , Khan Masood , Banner Davina , Driedger S. Michelle , Gainforth Heather L. , Graham Ian D. , Plamondon Katrina 
Published: November 2022

Background and objective
There has been growing emphasis on increasing impacts of academic health research by integrating research findings in healthcare. The concept of knowledge translation (KT) has been widely adopted in Canada to guide this work, although lack of recognition in tenure and promotion (T&P) structures have been identified as barrier to researchers undertaking KT. Our objective was to explore how KT is considered in institutional T&P documentation in Canadian academic health sciences.

Methods
We conducted content analysis of T&P documents acquired from 19 purposively sampled research-intensive or largest regional Canadian institutions in 2020–2021. We coded text for four components of KT (synthesis, dissemination, exchange, application). We identified clusters of related groups of documents interpreted together within the same institution. We summarized manifest KT content with descriptive statistics and identified latent categories related to how KT is considered in T&P documentation.

Results
We acquired 89 unique documents from 17 institutions that formed 48 document clusters. Most of the 1057 text segments were categorized as dissemination (n = 851, 81%), which was included in 47 document clusters (98%). 15 document clusters (31%) included all four KT categories, while one (2%) did not have any KT categories identified. We identified two latent categories: primarily implicit recognition of KT; and an overall lack of clarity on KT.

Conclusions
Our analysis of T&P documents from primarily research-intensive Canadian universities showed a lack of formal recognition for a comprehensive approach to KT and emphasis on traditional dissemination. We recommend that institutions explicitly and comprehensively consider KT in T&P and align documentation and procedures to reflect these values.