bluuebunny/crossref_metadata_2025_split huggingface dataset:
REKOVER study protocol: a pRospective patient treatment rEgistry of tramadol and dexKetoprofen trometamol oral fixed-dose combination (SKUDEXA) in mOderate to seVere acutE pain in Real-world setting in Asia
Authors: Ho Kok Yuen , Gyanwali Bibek , Dimayuga Cesar , Eufemio Edgar Michael , Bernardo Edwin , Raju Gopinathan , Chong Keen Wai , Waithayayothin Kritsadakorn , Ona Leonardo , Castro Marc Anthony L , Sawaddiruk Passakorn , Salvador Roehl C , Roohi Sharifah Ahmad , Tangwiwat Suwimon , Wilairatana Vajara , Oon Zhi Hao , Gupta Ankur , Nagrale Dinesh 
Published: March 2024

IntroductionSatisfactory management of acute pain remains a major medical challenge despite the availability of multiple therapeutic options including the fixed-dose combination (FDC) drugs. Tramadol and dexketoprofen trometamol (TRAM/DKP) 75/25 mg FDC was launched in 2018 in Asia and is widely used in the management of moderate to severe acute pain. There are limited data on its effectiveness and safety in Asian patients, and therefore, a need to better understand its usage patterns in clinical practice. We aim to understand the usage pattern of TRAM/DKP FDC, its effectiveness and tolerability in patients with moderate to severe acute pain in Asia.Methods and analysisREKOVER is a phase-IV, multicountry, multicentre, prospective, real-world observational study. A total of 750 postsurgical and non-surgical patients (male and female, aged 18–80 years) will be recruited from 13 tertiary-care hospitals (15 sites) in Singapore, Thailand, the Philippines and Malaysia. All patients prescribed with TRAM/DKP FDC and willing to participate in the study will be enrolled. The recruitment duration for each site will be 6 months. The severity of pain will be collected using Numeric Pain Rating Scale through the treatment period from day 1 to day 5, while satisfaction with the treatment will be evaluated using Patient Global Evaluation Scale at the end of treatment. Any adverse event reported during the study duration will be recorded for safety analysis (up to day 6). The study data will be entered into the ClaimIt portal and mobile application (app) (ObvioHealth, USA). All the inpatient data will be entered into the portal by the study site and for outpatient it will be done by patients through an app.Ethics and disseminationThe study has been approved by the local ethics committee from each study sites in Singapore, Thailand, the Philippines and Malaysia. Findings will be disseminated through local and global conference presentations, publications in peer-reviewed scientific journals and continuing medical education.
Can glycated haemoglobin (HbA1c) be used as a predictor of left ventricular diastolic dysfunction in non-hypertensive patients with newly diagnosed type 2 diabetes mellitus: a cross-sectional study at a tertiary care centre in Eastern India
Authors: Porel Rajdeep , Shyama Shyama , Ahmad Shaheen , Kumar Neeraj , Ahmad Shamshad , Biswas Ratnadeep , Ojha Vishnu Shankar 
Published: March 2024

ObjectivesThis study was conducted to establish the association between glycated haemoglobin (HbA1c) and left ventricular diastolic dysfunction (LVDD) in non-hypertensive patients with newly diagnosed type 2 diabetes mellitus (DM) and determine the cut-off value of HbA1c for detecting LVDD.DesignCross-sectional study.SettingThis study was conducted in General Medicine Department in collaboration with the Cardiology Department at All India Institute of Medical Sciences, Patna.ParticipantsThe study population comprised patients with newly diagnosed type 2 DM within the past 3 months, aged between 18 years and 80 years, who were not hypertensive and without any systemic diseases and who presented to the General Medicine Department.Primary and secondary outcome measuresThe presence of LVDD was the primary outcome measure.ResultsAmong the total of 60 participants, it was observed that age (adjusted odds ratio (AOR): 1.169, 95% CI: 1.066 to 1.283) and HbA1c (AOR: 2.625, 95% CI: 1.264 to 5.450) were found to be independent predictors for the presence of LVDD. Receiver operating characteristic analysis identified a cut-off value of HbA1c at 9.5% (80 mmol/mol) for detecting LVDD, with a specificity of 96.43%, a sensitivity of 37.5% and a positive predictive value (PPV) of 91.62%.ConclusionsThis study demonstrated that age and HbA1c levels are independent predictors of LVDD in patients with newly diagnosed type 2 DM without hypertension. A cut-off value of 9.5% for HbA1c was identified with a high specificity and PPV for predicting LVDD in patients with newly diagnosed type 2 diabetes. This underscores the importance of conducting echocardiography in patients with newly diagnosed asymptomatic type 2 diabetes with HbA1c 9.5% or more to assess LVDD, allowing for prompt interventions if necessary and to decelerate the progression towards heart failure.
SCALE-UP II: protocol for a pragmatic randomised trial examining population health management interventions to increase the uptake of at-home COVID-19 testing in community health centres
Authors: Del Fiol Guilherme , Orleans Brian , Kuzmenko Tatyana V , Chipman Jonathan , Greene Tom , Martinez Anna , Wirth Jennifer , Meads Ray , Kaphingst Kimberly K , Gibson Bryan , Kawamoto Kensaku , King Andy J , Siaperas Tracey , Hughes Shlisa , Pruhs Alan , Pariera Dinkins Courtney , Lam Cho Y , Pierce Joni H , Benson Ryzen , Borsato Emerson P , Cornia Ryan , Stevens Leticia , Bradshaw Richard L , Schlechter Chelsey R , Wetter David W 
Published: March 2024

IntroductionSCALE-UP II aims to investigate the effectiveness of population health management interventions using text messaging (TM), chatbots and patient navigation (PN) in increasing the uptake of at-home COVID-19 testing among patients in historically marginalised communities, specifically, those receiving care at community health centres (CHCs).Methods and analysisThe trial is a multisite, randomised pragmatic clinical trial. Eligible patients are >18 years old with a primary care visit in the last 3 years at one of the participating CHCs. Demographic data will be obtained from CHC electronic health records. Patients will be randomised to one of two factorial designs based on smartphone ownership. Patients who self-report replying to a text message that they have a smartphone will be randomised in a 2×2×2 factorial fashion to receive (1) chatbot or TM; (2) PN (yes or no); and (3) repeated offers to interact with the interventions every 10 or 30 days. Participants who do not self-report as having a smartphone will be randomised in a 2×2 factorial fashion to receive (1) TM with or without PN; and (2) repeated offers every 10 or 30 days. The interventions will be sent in English or Spanish, with an option to request at-home COVID-19 test kits. The primary outcome is the proportion of participants using at-home COVID-19 tests during a 90-day follow-up. The study will evaluate the main effects and interactions among interventions, implementation outcomes and predictors and moderators of study outcomes. Statistical analyses will include logistic regression, stratified subgroup analyses and adjustment for stratification factors.Ethics and disseminationThe protocol was approved by the University of Utah Institutional Review Board. On completion, study data will be made available in compliance with National Institutes of Health data sharing policies. Results will be disseminated through study partners and peer-reviewed publications.Trial registration numberClinicalTrials.gov:NCT05533918andNCT05533359.
Growth trajectory of full-term small-for-gestational-age infants: a 3-year longitudinal study in China
Authors: Zhang Jianwei , He Xinyu , Ma Lujia , Li Ziqiao , Shen Wenxia , Hua Mengdi , Sun Lidan , Bai Guannan 
Published: March 2024

ObjectiveSmall-for-gestational-age (SGA) infants are at risk of impaired growth and developmental outcomes, even for those who were born at full term. The growth trajectory of full-term SGA infants remains unknown. Therefore, this study aimed to evaluate the growth trajectory of full-term SGA infants from birth to 3 years old in East China.MethodsFull-term SGA infants were followed up from birth to 3 years old. The weight and length were measured at 3, 6, 12, 18, 24, 30 and 36 months. Rate of catch-up growth and rates of growth deviations including short stature, emaciation, underweight, overweight and obesity, were calculated at different time points. Latent class analysis was applied to describe growth trajectories from birth to 36 months.ResultsA total of 816 full-term SGA infants were enrolled in this study and 303 had complete follow-up data at 3, 6, 12, 18, 24, 30 and 36 months. At 24 months, the rate of catch-up growth was 42.4% in girls and 48.6% in boys; while at 36 months, this rate was 43.3% in girls and 52.1% in boys. The latent class analysis identified two trajectories of weight and length in boys and girls. Girls showed different growth trajectories of weight since 12 months compared with boys.ConclusionsOur study reported a relatively low rate of catch-up growth in full-term SGA infants and has identified different growth trajectories of length and weight in boys and girls. We call for attention from health professionals on the growth trajectory of full-term SGA infants to eventually promote their health potentials.
Pain sensitisation and joint inflammation in patients with active rheumatoid arthritis
Authors: Chaabo Khaldoun , Chan Estee , Garrood Toby , Rutter-Locher Zoe , Vincent Alex , Galloway James , Norton Sam , Kirkham Bruce W 
Published: March 2024

IntroductionDespite better therapies and strategies, many people with rheumatoid arthritis (RA) have persistent pain, often from abnormal pain processing, now termed nociplastic pain. However, RA patients with fibromyalgia (FM), a central nociplastic pain syndrome, also have power doppler ultrasound (PDUS+) joint inflammation. To understand the complex causes of pain, we performed clinical examination and patient-reported outcome measures (PROMs) plus comprehensive PDUS evaluation not previously combined.MethodsIn a cross-sectional study of sequential RA patients with at least moderate DAS28 erythrocyte sedimentation rate disease activity, we assessed 66/68 joints for swelling and tenderness, respectively, FM American College of Rheumatology 2010 diagnostic criteria, completed PROMs for function, quality of life and mood, alongside PDUS examination of 44 joints. Statistical analysis included logistic regression modelling and regularised (lasso) logistic regression methods.ResultsFrom 158 patients, 72 (46%) patients met FM criteria, with significantly worse tender joint counts and PROMs, but no differences in PDUS compared with the non-FM group. Categorising patients by PDUS+ joint presence and/or FM criteria, we identified four distinct groups: 43 (27.2%) patients with −FM−PD, 43 (27.2%) with −FM+PD, 42 (26.6%) with +FM−PD and 30 (19%) with +FM+PD. Both FM+ groups had worse PROMs for fatigue, mood and pain, compared with the FM− groups. We were unable to develop algorithms to identify different groups.ConclusionThe unexpected group −FM−PD group may have peripheral nociplastic pain, not commonly recognised in rheumatology. Only 46% of patients demonstrated PDUS+ inflammation. However clinical examination and PROMs did not reliably differentiate groups, emphasising PDUS remains an important tool.
Impact of national commissioning of pre-exposure prophylaxis (PrEP) on equity of access in England: a PrEP-to-need ratio investigation
Authors: Coukan Flavien , Sullivan Ann , Mitchell Holly , Jaffer Sajjida , Williams Andy , Saunders John , Atchison Christina , Ward Helen 
Published: March 2024

ObjectivesHIV pre-exposure prophylaxis (PrEP) is highly effective in preventing HIV acquisition. In England, NHS availability was limited to participants of the PrEP Impact Trial until late 2020. Some key populations at greater risk of HIV were under-represented in the trial suggesting inequities in trial PrEP access. We used the PrEP-to-need ratio (PnR; number of PrEP users divided by new HIV diagnoses) to investigate whether PrEP access improved following routine commissioning in October 2020 and identify populations most underserved by PrEP.MethodsAggregated numbers of people receiving ≥1 PrEP prescription and non-late new HIV diagnoses (epidemiological proxy for PrEP need) were taken from national surveillance data sets. We calculated the PnR across socio-demographics during Impact (October 2017 to February 2020; pre-COVID-19 pandemic) and post-commissioning PrEP era (2021) in England.ResultsPnR increased >11 fold, from 4.2 precommissioning to 48.9 in 2021, due to a fourfold reduction in non-late new HIV diagnoses and near threefold increase in PrEP users. PnR increased across genders, however, the men’s PnR increased 12-fold (from 5.4 precommissioning to 63.9 postcommissioning) while the women’s increased sevenfold (0.5 to 3.5). This increasing gender-based inequity was observed across age, ethnicity and region of residence: white men had the highest PnR, increasing >13 fold (7.1 to 96.0), while Black African women consistently had the lowest PnR, only increasing slightly (0.1 to 0.3) postcommissioning, suggesting they were the most underserved group. Precommissioning, the PnR was 78-fold higher among white men than Black women, increasing to 278-fold postcommissioning.ConclusionsDespite the overall increase in PrEP use, substantial PrEP Impact trial inequities widened postcommissioning in England, particularly across gender, ethnicity and region of residence. This study emphasises the need to guide HIV combination prevention based on equity metrics relative to the HIV epidemic. The PnR could support the optimisation of combination prevention to achieve zero new HIV infections in England by 2030.
Prevalence of lung cysts in adolescents and adults with a germlineDICER1pathogenic/likely pathogenic variant: a report from the National Institutes of Health and International Pleuropulmonary Blastoma/DICER1Registry
Authors: Nelson Alexander T , Vasta Lauren M , Watson Dave , Kim Jung , Harris Anne K , Best Ana F , Harney Laura A , Carr Ann G , Frederickson Nicole , Dehner Louis P , Kratz Christian P , Hagedorn Kelly N , Mize William A , Ling Alexander , Messinger Yoav H , Hill D Ashley , Schultz Kris Ann P , Stewart Douglas R 
Published: March 2024

BackgroundPleuropulmonary blastoma (PPB), the hallmark tumour associated withDICER1-related tumour predisposition, is characterised by an age-related progression from a cystic lesion (type I) to a high-grade sarcoma with mixed cystic and solid features (type II) or purely solid lesion (type III). Not all cystic PPBs progress; type Ir (regressed), hypothesised to represent regressed or non-progressed type I PPB, is an air-filled, cystic lesion lacking a primitive sarcomatous component. This study aims to evaluate the prevalence of non-progressed lung cysts detected by CT scan in adolescents and adults with germlineDICER1pathogenic/likely pathogenic (P/LP) variants.MethodsIndividuals were enrolled in the National Cancer Institute Natural History ofDICER1Syndrome study, the International PPB/DICER1Registry and/or the International Ovarian and Testicular Stromal Tumor Registry. Individuals with a germlineDICER1P/LP variant with first chest CT at 12 years of age or older were selected for this analysis.ResultsIn the combined databases, 110 individuals with a germlineDICER1P/LP variant who underwent first chest CT at or after the age of 12 were identified. Cystic lung lesions were identified in 38% (42/110) with a total of 72 cystic lesions detected. No demographic differences were noted between those with lung cysts and those without lung cysts. Five cysts were resected with four centrally reviewed as type Ir PPB.ConclusionLung cysts are common in adolescents and adults with germlineDICER1variation. Further study is needed to understand the mechanism of non-progression or regression of lung cysts in childhood to guide judicious intervention.
Probing the magnetic field strength dependence of the chiral magnetic effect
Authors: Christakoglou Panos 
Published: March 2024

AbstractThe article presents a study aimed at probing the dependence of the Chiral Magnetic Effect (CME) on the magnetic field strength using the Anomalous Viscous Fluid Dynamics (AVFD) model in Pb–Pb at LHC energies. The results demonstrate the quadratic dependence of the correlators used for the study of the CME in heavy ion collisions on the number of spectators, a proxy of the magnitude of the magnetic field. The article also presents the extension of this approach to a two dimensional space, formed by both the aforementioned proxy of the magnetic field strength but also a proxy of the final state ellipticity, a key ingredient of the background in these measurements, for each centrality interval. This provides an exciting possibility to experiments to isolate the background contributions from the potential CME signal.
Collisions and dynamics of particles with magnetic dipole moment and electric charge near magnetized rotating Kerr black holes
Authors: Jumaniyozov Shokhzod , Khan Saeed Ullah , Rayimbaev Javlon , Abdujabbarov Ahmadjon , Ahmedov Bobomurat 
Published: March 2024

AbstractAnalysis of test magnetized and charged particles around black holes immersed in external magnetic fields may help to explain the observed astrophysical phenomena related to black holes, such as the acceleration of particles up to high energies. In this sense, we studied the circular motion of test-charged particles with magnetic dipole orbiting around magnetized rotating Kerr black holes. First, we derive the effective potential for the circular motion of such particles, including interactions between the external magnetic field and the electric charge, and the magnetic interaction between the magnetic dipole. In addition, we analyze the angular momentum and energy of particles corresponding to circular orbits. The effects of magnetic interaction and coupling parameters on the position of innermost stable circular orbits (ISCOs), the energy and angular momentum of the particles at ISCO, and the energy efficiency from the Novikov-Thorne accretion disc have been investigated. We also find cases of degeneracy between magnetic dipole interaction and magnetic coupling parameters, giving the same ISCO radius. Finally, we studied various cases of collisions of neutral, magnetized, and electrically charged particles near rotating Kerr black holes in the presence of external magnetic fields. The critical angular momentum of spinning charged particles is found in which the particles can collide. We also analyze the effects of both magnetic interactions on the center-of-mass energy of the colliding particles.
Weyl quadratic gravity as a gauge theory and non-metricity vs torsion duality
Authors: Condeescu C. , Ghilencea D. M. , Micu A. 
Published: March 2024

AbstractWe review (non-supersymmetric) gauge theories of four-dimensional space-time symmetries and their quadratic action. The only true gauge theory of such a symmetry (with a physical gauge boson) that has an exact geometric interpretation, generates Einstein gravity in its spontaneously broken phase and is anomaly-free, is that of Weyl gauge symmetry (of dilatations). Gauging the full conformal group does not generate a true gauge theory of physical (dynamical) associated gauge bosons. Regarding the Weyl gauge symmetry, it is naturally realised in Weyl conformal geometry, where it admits two different but equivalent geometric formulations, of same quadratic action: one non-metric but torsion-free, the other Weyl gauge-covariant and metric (with respect to a new differential operator). To clarify the origin of this intriguing result, a third equivalent formulation of this gauge symmetry is constructed using the standard, modern approach on the tangent space (uplifted to space-time by the vielbein), which is metric but has vectorial torsion. This shows an interesting duality vectorial non-metricity vs vectorial torsion of the corresponding formulations, related by a projective transformation. We comment on the physical meaning of these results.
The origin of the cosmological constant in unimodular gravity
Authors: Álvarez Enrique , Anero Jesús , Sánchez-Ruiz Irene 
Published: March 2024

AbstractIt is well-known that in unimodular gravity (UG) the cosmological constant is not sourced by a constant energy density, but rather appears as some sort of integration constant. In this work we try to flesh this out by studying in some detail a couple of examples, one from cosmology and the other from gravitational collapse.
The CDK4/6 Inhibitor Palbociclib Synergizes with ATRA to Induce Differentiation in AML
Authors: Hu Linhui , Li Qian , Wang Jiyu , Wang Huiping , Ren Xiyang , Huang Keke , Wang Yangyang , Liang Xue , Pu Lianfang , Xiong Shudao , Zhai Zhimin 
Published: March 2024

Abstract
Differentiation therapy based on ATRA almost cured acute promyelocytic leukemia (APL). However, it is disappointing that ATRA is not effective against other acute myeloid leukemia (AML) subtypes. Developing new and effective anti-AML therapies that promote leukemia differentiation is necessary. The CDK4/6-cyclin D pathway is a key initiator of the G1–S phase transition, which determines cell fate. Herein, we investigated whether the CDK4/6 inhibitor palbociclib would synergize with ATRA to promote leukemia differentiation in vitro and in vivo. Our findings revealed that CDK4/6-cyclin D pathway genes were aberrantly expressed in AML, and we observed that palbociclib sensitized AML cells to ATRA-induced morphologic, biochemical, and functional changes indicative of myeloid differentiation. The combination of palbociclib and ATRA attenuated AML cell expansion in vivo. These enhanced differentiation effects may be associated with the regulation of transcription factors, including RARα, E2F1, and STAT1. Overall, our findings demonstrate that CDK4/6 inhibition sensitizes AML cells to ATRA and could guide the development of novel therapeutic strategies for patients with AML.
Regional Variation in Cardiovascular Genes Enables a Tractable Genome Editing Strategy
Authors: Krysov Vikki A. , Wilson Rachel H. , Ten Nicholas S. , Youlton Nathan , De Jong Hannah N. , Sutton Shirley , Huang Yong , Reuter Chloe M. , Grove Megan E. , Wheeler Matthew T. , Ashley Euan A. , Parikh Victoria N. 
Published: March 2024

BACKGROUND:
To realize the potential of genome engineering therapeutics, tractable strategies must be identified that balance personalized therapy with the need for off-the-shelf availability. We hypothesized that regional clustering of pathogenic variants can inform the design of rational prime editing therapeutics to treat the majority of genetic cardiovascular diseases with a limited number of reagents.

METHODS:
We collated 2435 high-confidence pathogenic/likely pathogenic (P/LP) variants in 82 cardiovascular disease genes from ClinVar. We assessed the regional density of these variants by defining a regional clustering index. We then combined a highly active base editor with prime editing to demonstrate the feasibility of a P/LP hotspot-directed genome engineering therapeutic strategy in vitro.

RESULTS:
P/LP variants in cardiovascular disease genes display higher regional density than rare variants found in the general population. P/LP missense variants displayed higher average regional density than P/LP truncating variants. Following hypermutagenesis at a pathogenic hotspot, mean prime editing efficiency across introduced variants was 57±27%.

CONCLUSIONS:
Designing therapeutics that target pathogenic hotspots will not only address known missense P/LP variants but also novel P/LP variants identified in these hotspots as well. Moreover, the clustering of P/LP missense rather than truncating variants in these hotspots suggests that prime editing technology is particularly valuable for dominant negative disease. Although prime editing technology in relation to cardiac health continues to improve, this study presents an approach to targeting the most impactful regions of the genome for inherited cardiovascular disease.