bluuebunny/crossref_metadata_2025_split huggingface dataset:
An opportunity to be grateful for? Exploring discourses about international medical graduates from India and Pakistan to the UK between 1960 and 1980
Authors: Arfeen Zakia , Diaz Brett , Whitehead Cynthia Ruth , Rashid Mohammed Ahmed 
Published: June 2024

IntroductionFollowing India and Pakistan gaining independence from British colonial rule, many doctors from these countries migrated to the UK and supported its fledgling National Health Service (NHS). Although this contribution is now widely celebrated, these doctors often faced hardship and hostility at the time and continue to face discrimination and racism in UK medical education. This study sought to examine discursive framings about Indian and Pakistani International Medical Graduates (IPIMGs) in the early period of their migration to the UK, between 1960 and 1980.MethodsWe assembled a textual archive of publications relating to IPIMGs in the UK during this time period inThe BMJ. We employed critical discourse analysis to examine knowledge and power relations in these texts, drawing on postcolonialism through the contrapuntal approach developed by Edward Said.ResultsThe dominant discourse in this archive was one of opportunity. This included the opportunity for training, which was not available to IPIMGs in an equitable way, the missed opportunity to frame IPIMGs as saviours of the NHS rather than ‘cheap labour’, and the opportunity these doctors were framed to be held by being in the ‘superior’ British system, for which they should be grateful. Notably, there was also an opportunity to oppose, as IPIMGs challenged notions of incompetence directed at them.ConclusionAs IPIMGs in the UK continue to face discrimination, we shed light on how their cultural positioning has been historically founded and engrained in the imagination of the British medical profession by examining discursive trends to uncover historical tensions and contradictions.
Association between profiles of accelerometer-measured daily movement behaviour and mortality risk: a prospective cohort study of British older adults
Authors: Yerramalla Manasa Shanta , Chen Mathilde , Dugravot Aline , van Hees Vincent T , Sabia Severine 
Published: June 2024

ObjectivesWe identified profiles of wake-time movement behaviours (sedentary behaviours, light intensity physical activity and moderate-to-vigorous physical activity) based on accelerometer-derived features among older adults and then examined their association with all-cause mortality.MethodsData were drawn from a prospective cohort of 3991 Whitehall II accelerometer substudy participants aged 60–83 years in 2012–2013. Daily movement behaviour profiles were identified using k-means cluster analysis based on 13 accelerometer-assessed features characterising total duration, frequency, bout duration, timing and activity intensity distribution of movement behaviour. Cox regression models were used to assess the association between derived profiles and mortality risk.ResultsOver a mean follow-up of 8.1 (SD 1.3) years, a total of 410 deaths were recorded. Five distinct profiles were identified and labelled as ‘active’ (healthiest), ‘active sitters’, ‘light movers’, ‘prolonged sitters’, and ‘most sedentary’ (most deleterious). In model adjusted for sociodemographic, lifestyle, and health-related factors, compared with the ‘active’ profile, ‘active sitters’ (HR 1.57, 95% CI 1.01 to 2.44), ‘light movers’ (HR 1.75, 95% CI 1.17 to 2.63), ‘prolonged sitters’ (HR 1.67, 95% CI 1.11 to 2.51), ‘most sedentary’ (HR 3.25, 95% CI 2.10 to 5.02) profiles were all associated with a higher risk of mortality.ConclusionGiven the threefold higher mortality risk among those with a ‘most sedentary’ profile, public health interventions may target this group wherein any improvement in physical activity and sedentary behaviour might be beneficial.
Sanctioned illegal high tackles significantly increase concussion risk to both tacklers and ball carriers in elite men’s Rugby Union
Authors: Tucker Ross , Hester Ben , Hendricks Sharief , Brown James , Falvey Éanna C 
Published: June 2024

ObjectivesTackles making contact above the sternum increase concussion and head injury assessment (HIA) risk in Rugby Union. The sport has introduced harsher sanctions to change tackler behaviours to reduce this risk. This increased high tackle sanction numbers, though it is unknown whether sanction severity is associated with injury risk.MethodsThe sanction decision made by match officials for tackles resulting in 157 HIA1 removals, of which 91 were confirmed concussions, was evaluated. The propensity of sanction types, ranging from no foul play to red card, was compared after calculating concussion and HIA1 numbers per 1000 tackles of each sanction, using total tackle number of each sanction type from one season of two elite professional competitions.ResultsHIA1 removal and concussion risk increased as sanction severity increased. Red-carded tackles were 271.5 (95% CI 143.8 to 512.6) times more likely to result in concussions than legal tackles. Tacklers and ball carriers were more likely to experience concussions from sanctioned high tackles, with tackler risk 28.5 (95% CI 13.5 to 59.9) times higher for sanctioned high tackles compared with legal tackles, and ball carrier risk elevated 133.7-fold (95% CI 65.5 to 272.8) after sanctioned high tackles.ConclusionSanctioned high tackles significantly increase concussion and HIA1 risk to both tacklers and ball carriers. Current decision-making frameworks that guide sanction decisions do identify tackle behaviours that elevate clinical risk. Both tacklers and ball carriers would be less likely to experience concussions and head injuries if the frequency of illegal high tackles is decreased.
Obesity is associated with muscle atrophy in rotator cuff tear
Authors: Herzberg Simone D , Zhao Zhiguo , Freeman Thomas H , Prakash Ravi , Kuhn John E , Khazzam Michael S , Matzkin Elizabeth G , Baumgarten Keith M , Bishop Julie Y , Brophy Robert H , Carey James L , Dunn Warren R , Jones Grant L , Ma C Benjamin , Marx Robert G , McCarty Eric C , Poddar Sourav K , Smith Matthew V , Spencer Edwin E , Vidal Armando F , Wolf Brian R , Wright Rick W , Jain Nitin B , Giri Ayush 
Published: June 2024

ObjectiveThe primary goal of this study is to evaluate the relationship between Body Mass Index (BMI) and muscle atrophy in individuals with rotator cuff tears.MethodsThis study consists of patients with rotator cuff tears identified by MRI from two independent cohorts, the Rotator Cuff Outcomes Workgroup (ROW) and the Multicenter Orthopaedic Outcomes Network (MOON). Presence of atrophy (yes/no) and severity of atrophy (as an ordinal variable) were assessed on MRI by expert physicians. We used multivariable regression models to evaluate the relationship between BMI and muscle atrophy while adjusting for age and sex in each study, conducted sensitivity analyses for full-thickness tear and combined results using inverse variance-weighted meta-analysis.ResultsA total of 539 patients (MOON=395, ROW=144) from the combined cohorts had MRI data available on muscle atrophy. Among these patients, 246 (46%) had atrophy of at least one of the muscles of the rotator cuff and 282 (52%) had full-thickness tears. In meta-analysis across both cohorts, each 5 kg/m2increase in BMI was associated with a 21% (aOR=1.21, 95% CI=1.02, 1.43) increased odds of having muscle atrophy among individuals with any tear size, and 36% (aOR=1.36, 95% CI=1.01–1.81) increased odds among individuals with full-thickness tear.ConclusionsHigher BMI was associated with significantly higher odds of muscle atrophy in patiens with rotator cuff tears. More study is needed to unders1tand why and how this relationship exists, as well as whether interventions to reduce BMI may help improve outcomes for these patients.Level of EvidenceIII.
Anti-dsDNA IgE: a potential non-invasive test for prediction of lupus nephritis relapse
Authors: Himbert Marie , Jourde-Chiche Noémie , Chapart Léa , Charles Nicolas , Baumstarck Karine , Daugas Eric 
Published: June 2024

ObjectivesDiscontinuation or continuation of maintenance immunosuppressive therapy (MIST) after a severe lupus nephritis (LN) requires measuring the risk of relapse but reliable clinical and biological markers are lacking. The WIN-IgE study assesses the value of serum anti-dsDNA IgE autoantibodies as a biomarker for the prediction of relapse in severe LN.MethodsWIN-IgE is an ancillary study of the WIN-Lupus study (NCT01284725), a prospective controlled clinical trial which evaluated the discontinuation of MIST after 2–3 years in class III or IV±V LN with active lesions. WIN-IgE included all patients with available serum collected at randomisation for continuation or discontinuation of MIST. In these sera, anti-dsDNA antibodies, IgE and IgG, were quantified by ELISA and compared between patients who experienced LN relapse and those who did not during the 24 months of follow-up.Results52 patients were included, 25 in the MIST continuation group and 27 in the MIST discontinuation group, 12 experienced a biopsy-proven relapse of LN. Initial anti-dsDNA IgE antibodies levels were higher in patients with subsequent LN relapse. Anti-dsDNA IgG was not associated with relapse. Survival without LN relapse was lower in patients with anti-dsDNA IgE levels above vs below a threshold of 1.9 arbitrary units (p=0.019), particularly in the subgroup of patients randomised to discontinue MIST (p=0.002). In all patients, anti-dsDNA IgE above 1.9 arbitrary units had a positive predictive value of 0.8 for severe LN relapse.ConclusionsThese results suggest blood anti-dsDNA IgE as a non-invasive predictive marker of LN relapse.
Nipocalimab, an anti-FcRn monoclonal antibody, in participants with moderate to severe active rheumatoid arthritis and inadequate response or intolerance to anti-TNF therapy: results from the phase 2a IRIS-RA study
Authors: Taylor Peter C , Schett Georg , Huizinga Tom WJ , Wang Qingmin , Ibrahim Fowzia , Zhou Bei , Liva Sophia G , Shaik Jafar Sadik B , Xiong Yuan , Leu Jocelyn H , Panchakshari Rohit A , Loza Matthew J , Ma Keying , Dhatt Harman , Rojo Cella Ricardo , Karyekar Chetan S , Cuff Carolyn A , Gao Sheng , Fei Kaiyin 
Published: June 2024

ObjectivesTo investigate the efficacy, safety, pharmacokinetics and pharmacodynamics of nipocalimab in participants with moderate to severe active rheumatoid arthritis (RA) and inadequate response or intolerance to ≥1 antitumour necrosis factor agent.MethodsIn this phase 2a study, participants with RA seropositive for anticitrullinated protein antibodies (ACPA) or rheumatoid factors were randomised 3:2 to nipocalimab (15 mg/kg intravenously every 2 weeks) or placebo from Weeks 0 to 10. Efficacy endpoints (primary endpoint: change from baseline in Disease Activity Score 28 using C reactive protein (DAS28-CRP) at Week 12) and patient-reported outcomes (PROs) were assessed through Week 12. Safety, pharmacokinetics and pharmacodynamics were assessed through Week 18.Results53 participants were enrolled (nipocalimab/placebo, n=33/20). Although the primary endpoint did not reach statistical significance for nipocalimab versus placebo, a numerically higher change from baseline in DAS28-CRP at Week 12 was observed (least squares mean (95% CI): –1.03 (–1.66 to –0.40) vs –0.58 (–1.24 to 0.07)), with numerically higher improvements in all secondary efficacy outcomes and PROs. Serious adverse events were reported in three participants (burn infection, infusion-related reaction and deep vein thrombosis). Nipocalimab significantly and reversibly reduced serum immunoglobulin G, ACPA and circulating immune complex levels but not serum inflammatory markers, including CRP. ACPA reduction was associated with DAS28-CRP remission and 50% response rate in American College of Rheumatology (ACR) criteria; participants with a higher baseline ACPA had greater clinical improvement.ConclusionsDespite not achieving statistical significance in the primary endpoint, nipocalimab showed consistent, numerical efficacy benefits in participants with moderate to severe active RA, with greater benefit observed for participants with a higher baseline ACPA.Trial registration numberNCT04991753.
Nonmetric geometric flows and quasicrystalline topological phases for dark energy and dark matter in $$f(Q)$$ cosmology
Authors: Bubuianu Laurenţiu , Nurlan Erik , Seti Julia O. , Vacaru Sergiu I. , Veliev Elşen Veli 
Published: June 2024

AbstractWe elaborate on nonmetric geometric flow theory and metric-affine gravity with applications in modern cosmology. Two main motivations for our research follow from the facts that (1) cosmological models for f(Q) modified gravity theories, MGTs, are efficient for describing recent observational data provided by the James Webb Space Telescope; and (2) the statistical thermodynamic properties of such nonmetric locally anisotropic cosmological models can be studied using generalizations of the concept of G. Perelman entropy. We derive nonmetric distorted R. Hamilton and Ricci soliton equations in such canonical nonholonomic variables when corresponding systems of nonlinear PDEs can be decoupled and integrated in general off-diagonal forms. This is possible if we develop and apply the anholonomic frame and connection deformation method involving corresponding types of generating functions and generating sources encoding nonmetric distortions. Using such generic off-diagonal solutions (when the coefficients of metrics and connections may depend generically on all spacetime coordinates), we model accelerating cosmological scenarios with quasi-periodic gravitational and (effective) matter fields; and study topological and nonlinear geometric properties of respective dark energy and dark matter, DE and DM, models. As explicit examples, we analyze some classes of nonlinear symmetries defining topological quasicrystal, QC, phases which can modified to generate other types of quasi-periodic and locally anisotropic structures. The conditions when such nonlinear systems possess a behaviour which is similar to that of the Lambda cold dark matter ($$\Lambda $$
Λ
CDM) scenario are stated. We conclude that nonmetric geometric and cosmological flows can be considered as an alternative to the $$\Lambda $$
Λ
CDM concordance models and speculate on how such theories can be elaborated. This is a partner work with generalizations and applications of the results published by Bubuianu, Vacaru et all. EPJC 84 (2024) 211; 80 (2020) 639; 78 (2018) 393; 78 (2018) 969; and CQG 35 (2018) 245009.
Profile update: the effects of identity disclosure on network connections and language
Authors: Choi Minje , Romero Daniel M. , Jurgens David 
Published: June 2024

AbstractOur social identities determine how we interact and engage with the world surrounding us. In online settings, individuals can make these identities explicit by including them in their public biography, possibly signaling a change in what is important to them and how they should be viewed. While there is evidence suggesting the impact of intentional identity disclosure in online social platforms, its actual effect on engagement activities at the user level has yet to be explored. Here, we perform the first large-scale study on Twitter that examines behavioral changes following identity disclosure on Twitter profiles. Combining social networks with methods from natural language processing and quasi-experimental analyses, we discover that after disclosing an identity on their profiles, users (1) tweet and retweet more in a way that aligns with their respective identities, and (2) connect more with users that disclose similar identities. We also examine whether disclosing the identity increases the chance of being targeted for offensive comments and find that in fact (3) the combined effect of disclosing identity via both tweets and profiles is associated with a reduced number of offensive replies from others. Our findings highlight that the decision to disclose one’s identity in online spaces can lead to substantial changes in how they express themselves or forge connections, with a lesser degree of negative consequences than anticipated.
Neural intelligent approach for heat transfer applications of trihybrid cross bio-nanofluid over wedge geometry
Authors: Ayub Assad , Iqbal Zahoor , Shah Syed Zahir Hussain , Al Samman Fathia M. , Wahab Hafiz Abdul , Dalam Mhassen E. E. , Gargouri Ameni 
Published: June 2024

Significance: Heat transport in the blood within a wedge-shaped artery is significant in biomedical engineering field like develop therapeutic strategies, drug delivery to specific regions of the artery, vicinity of narrowed or blocked arteries and catheter-based treatments such as angioplasty or thermal ablation. Motive: This study investigates the heat transport analysis of trihybrid nanofluid (blood) over wedge-shaped artery with mathematical model of Cross fluid. This study incorporates three nanoparticles, graphene oxide (GO), titanium dioxide (TiO2), and aluminum oxide (Al2O3) in base fluid blood. The wedge-shaped artery is chosen due to its relevance to biomedical applications and it reflects the nature of blood flow in real vascular structures. Heat transport is scrutinized through thermal radiations and flow rate is inspected through inclined magnetic field. Methodology: The bvp4c and Levenberg–Marquardt Neural Network (LM-NN) supervised neural scheme is used to predict the numerical outcome of this study. Findings: Incorporation of nanoparticles made rapid heat transport of blood in wedge-shaped artery. Velocity of blood is decreased with high Weissenberg number and magnetic force. The temperature of a blood in a wedge-shaped artery increases with positive non-uniform heat source/sink parameters and decreases with negative non-uniform heat source/sink parameters.
A Phase I/II Study of Valemetostat (DS-3201b), an EZH1/2 Inhibitor, in Combination with Irinotecan in Patients with Recurrent Small-Cell Lung Cancer
Authors: Choudhury Noura J. , Lai W. Victoria , Makhnin Alex , Heller Glenn , Eng Juliana , Li Bob , Preeshagul Isabel , Santini Fernando C. , Offin Michael , Ng Kenneth , Paik Paul , Larsen Christina , Ginsberg Michelle S. , Lau Yvonne , Zhang Xinyuan , Baine Marina K. , Rekhtman Natasha , Rudin Charles M. 
Published: June 2024

Abstract

Purpose:
Recurrent small-cell lung cancer (SCLC) has few effective treatments. The EZH2-SLFN11 pathway is a driver of acquired chemoresistance that may be targeted.

Patients and Methods:
This phase I/II trial investigated valemetostat, an EZH1/2 inhibitor, with fixed-dose irinotecan in patients with recurrent SCLC. Phase I primary objectives were to assess safety, tolerability, and a recommended phase II dose (RP2D). The phase II primary objective was overall response rate (ORR), with secondary objectives of determining duration of response (DoR), progression-free survival (PFS), and overall survival (OS). Correlative analyses included immunohistochemistry of pretreatment and on-treatment tumor biopsies and pharmacokinetics analysis.

Results:
Twenty-two patients were enrolled (phase I, n = 12; phase II, n = 10); one withdrew consent prior to treatment. Three dose-limiting toxicities (DLT) in dose-escalation resulted in valemetostat 100 mg orally daily selected as RP2D. Among 21 evaluable patients, the most frequent (≥20%) treatment-related adverse events were diarrhea, fatigue, nausea, and rash; three patients discontinued treatment for toxicity. Three of the first 10 patients in phase II experienced DLTs triggering a stopping rule. The ORR was 4/19 or 21% [95% confidence interval (CI), 6%–46%]. The median DoR, PFS, and OS were 4.6 months, 2.2 months (95% CI, 1.3–7.6 months), and 6.6 months (95% CI, 4.3 to not reached), respectively. SLFN11/EZH2 expression and SCLC subtyping markers did not correlate with response, but MHC-I expression did increase with treatment. Two responders demonstrated subtype switching on treatment.

Conclusions:
Combination valemetostat and irinotecan was not tolerated but demonstrated efficacy in recurrent SCLC. Valemetostat, combined with agents without overlapping toxicity, warrants further investigation in SCLC.
FZ-AD005, a Novel DLL3-Targeted Antibody–Drug Conjugate with Topoisomerase I Inhibitor, Shows Potent Antitumor Activity in Preclinical Models
Authors: Guo Qingsong , Gao Bei , Song Ruiwen , Li Weinan , Zhu Shulei , Xie Qian , Lou Sensen , Wang Lei , Shen Jiafei , Zhao Teng , Zhang Yifan , Wu Jinsong , Lu Wei , Yang Tong 
Published: June 2024

Abstract
Delta-like ligand 3 (DLL3) is overexpressed in small cell lung cancer (SCLC) and has been considered an attractive target for SCLC therapy. Rovalpituzumab tesirine was the first DLL3-targeted antibody–drug conjugate (ADC) to enter clinical studies. However, serious adverse events limited progress in the treatment of SCLC with rovalpituzumab tesirine. In this study, we developed a novel DLL3-targeted ADC, FZ-AD005, by using DXd with potent cytotoxicity and a relatively better safety profile to maximize the therapeutic index. FZ-AD005 was generated by a novel anti-DLL3 antibody, FZ-A038, and a valine–alanine (Val–Ala) dipeptide linker to conjugate DXd. Moreover, Fc-silencing technology was introduced in FZ-AD005 to avoid off-target toxicity mediated by FcγRs and showed negligible Fc-mediated effector functions in vitro. In preclinical evaluation, FZ-AD005 exhibited DLL3-specific binding and demonstrated efficient internalization, bystander killing, and excellent in vivo antitumor activities in cell line–derived xenograft and patient-derived xenograft models. FZ-AD005 was stable in circulation with acceptable pharmacokinetic profiles in cynomolgus monkeys. FZ-AD005 was well tolerated in rats and monkeys. The safety profile of FZ-AD005 was favorable, and the highest nonseverely toxic dose was 30 mg/kg in cynomolgus monkeys. In conclusion, FZ-AD005 has the potential to be a superior DLL3-targeted ADC with a wide therapeutic window and is expected to provide clinical benefits for the treatment of patients with SCLC.