bluuebunny/crossref_metadata_2025_split huggingface dataset:
Metformin in the prevention of type 2 diabetes after gestational diabetes in postnatal women (OMAhA): a UK multicentre randomised, placebo-controlled, double-blind feasibility trial with nested qualitative study
Authors: Bolou Angeliki , Drymoussi Zoe , Lanz Doris , Amaefule Chiamaka Esther , Gonzalez Carreras Francisco Jose , Pardo Llorente Maria del Carmen , Dodds Julie , Pizzo Elena , Thomas Amy , Heighway James , Harden Angela , Sanghi Anita , Hitman Graham , Zamora Javier , Pérez Teresa , Huda Mohammed S B , Thangaratinam Shakila 
Published: November 2023

ObjectiveTo determine the feasibility of a definitive trial of metformin to prevent type 2 diabetes in the postnatal period in women with gestational diabetes.DesignA multicentre, placebo-controlled, double-blind randomised feasibility trial with qualitative evaluation.SettingThree inner-city UK National Health Service hospitals in London.ParticipantsPregnant women with gestational diabetes treated with medication.Interventions2 g of metformin (intervention) or placebo (control) from delivery until 1 year postnatally.Primary outcome measuresRates of recruitment, randomisation, follow-up, attrition and adherence to the intervention.Secondary outcome measuresPreliminary estimates of glycaemic effects, qualitative exploration, acceptability of the intervention and costs.ResultsOut of 302 eligible women, 57.9% (175/302) were recruited. We randomised 82.3% (144/175) of those recruited, with 71 women in the metformin group and 73 women in the placebo group. Of the participants remaining in the study and providing any adherence information, 54.1% (59/109) took at least 75% of the target intervention dose; the overall mean adherence was 64% (SD 33.6). Study procedures were found to be acceptable to women and healthcare professionals. An increased perceived risk of developing type 2 diabetes, or a positive experience of taking metformin during pregnancy, encouraged participation and adherence to the intervention. Barriers to adherence included disruption to the medication schedule caused by the washout periods ahead of each study visit or having insufficient daily reminders.ConclusionsIt is feasible to run a full-scale definitive trial on the effectiveness of metformin to prevent type 2 diabetes in women with gestational diabetes, during the early postnatal period. Adherence and engagement with the study could be improved with more regular reminders and potentially the addition of ongoing educational or peer support to reinforce messages around type 2 diabetes prevention.Trial registration numberISRCTN20930880.
Comparison of drug-coated balloon angioplasty versus standard medical therapy on recurrent stroke and mortality rates among patients with symptomatic intracranial atherosclerotic stenosis: protocol for a systematic review and meta-analysis
Authors: Sun Yixin , Luo Jichang , Gong Haozhi , Xu Ran , Zhang Xiao , Yang Bin , Ma Yan , Wang Tao , Jiao Liqun 
Published: November 2023

IntroductionStroke remains the second leading cause of death worldwide, a common cause of which is intracranial atherosclerotic stenosis (ICAS). Medical treatment is recommended as first-line therapy for treating ICAS, but the recurrence rate remains high. Drug-coated balloon (DCB) angioplasty has been designed to lower the risk of recurrent stenosis, holding therapeutic promise in the treatment of ICAS. However, the benefits of DCB require further evaluation.Methods and analysisThe Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols was followed to develop this protocol. We will systematically search online databases including Cochrane Central Register of Controlled Trials, PubMed, Web of Science, EMBASE, China Biological Medicine Database, ClinicalTrials.gov and WHO ICTRP from 1 January 2011 to the date of search. This will be supplemented by a manual search of unpublished and ongoing trials to manually select articles for inclusion. Inclusion criteria are randomised or quasi-randomised clinical trials and observational studies that investigated DCB or medical treatment for patients with a symptomatic ICAS of 50%–99%. The primary outcome is short-term composite safety including death of any cause, or non-fatal stroke. Secondary outcomes include long-term death or stroke, restenosis, neurological rehabilitation, quality of life and other complications. The available data will be analysed using meta-analysis, if appropriate. The evaluation of heterogeneity and biases will be guided by the Cochrane Handbook for Systematic Reviews of Interventions.Ethics and disseminationThis systematic review does not require ethical approval as all available data from eligible studies will be anonymous with no concerns regarding privacy. Our findings will be disseminated through international conferences and peer-reviewed publications. Additional data from the study are available on request to corresponding authors via email.PROSPERO registration numberCRD42022341607.
High-dose versus low-dose intravenous nitroglycerine for sympathetic crashing acute pulmonary edema: a randomised controlled trial
Authors: Siddiqua Naazia , Mathew Roshan , Sahu Ankit Kumar , Jamshed Nayer , Bhaskararayuni Jyothiswaroop , Aggarwal Praveen , Kumar Akshay , Khan Maroof Ahmad 
Published: November 2023

ObjectivesSympathetic crashing acute pulmonary edema (SCAPE) is a subset of heart failure with a dramatic presentation. The unique physiology of this condition requires a different management strategy from the conventional practice. The trial objective was to compare the efficacy of high-dose and low-dose GTN in patients with SCAPE.MethodsThis was an open-label randomised control trial conducted in a tertiary care teaching hospital in India from 11 November 2021 to 30 November 2022. Consenting participants were randomised to high-dose GTN or conventional low-dose GTN. The primary outcome was symptom resolution at 6 hours and 12 hours. Secondary outcomes included intubation rates, admission rates, length of hospital stay, and any short-term adverse effects of GTN and major adverse cardiac events (MACE) at 30 days.ResultsFifty-four participants were included (26 high-dose GTN, 26 low-dose GTN). At 6 hours, symptom resolution was seen in 17 patients (65.4%) in the 'high-dose' group, compared with 3 (11.5%) in the 'low-dose' group (p<0.001). At 12 hours, 88.5% of patients had a clinical resolution in the 'high-dose' arm versus 19.5% in 'low-dose' arm . The low-dose group had longer median hospital stay (12 hours vs 72 hours), more frequent MACE (3.8% vs 26.9%, p=0.02) and a higher intubation rate (3.8% vs 19.2%, p=0.08). The only short-term adverse effect seen was a headache in both the groups.ConclusionIn SCAPE, patients receiving high-dose GTN (>100 mcg/min) had earlier symptom resolution compared with the conventional ‘low dose’ GTN without any significant adverse effects.Trial registrationClinical trial registry of India (CTRI/2021/11/037902).
Sexual orientation, gender expression and socioeconomic status in the National Longitudinal Study of Adolescent to Adult Health
Authors: Hernandez Stephanie M. , Halpern Carolyn T. , Conron Kerith J. 
Published: November 2023

BackgroundSocioeconomic status (SES) is a fundamental contributor to health, yet it is rarely examined relative to gender expression, particularly gender non-conformity and sexual orientation.MethodsWe use data from 11 242 Wave V respondents (aged 33–44) in the National Longitudinal Study of Adolescent to Adult Health (2016–2018) to examine associations between socially assigned gender expression, sexual orientation and SES, in logistic and multinomial regression models stratified by sex assigned at birth.ResultsAmong both women and men a general pattern of heightened risk for lower SES among gender non-conforming sexual minorities relative to gender conforming heterosexuals was observed. Gender non-conforming heterosexuals were also at elevated risk of lower SES compared with their conforming heterosexual peers.ConclusionSocioeconomic differences by sexual orientation and gender expression have important implications for understanding health disparities among gender non-conforming sexual minorities and their gender conforming heterosexual counterparts.
Randomized, open-label, phase II, biomarker study of immune-mediated mechanism of action of neoadjuvant subcutaneous trastuzumab in patients with locally advanced, inflammatory, or early HER2-positive breast cancer—Immun-HER trial (GOIRC-01-2016)
Authors: Pellegrino Benedetta , Tommasi Chiara , Serra Olga , Gori Stefania , Cretella Elisabetta , Ambroggi Massimo , Frassoldati Antonio , Bisagni Giancarlo , Casarini Chiara , Bria Emilio , Carbognin Luisa , Fiorio Elena , Mura Antonella , Zamagni Claudio , Gianni Lorenzo , Zambelli Alberto , Montemurro Filippo , Tognetto Michele , Todeschini Renata , Missale Gabriele , Campanini Nicoletta , Silini Enrico Maria , Maglietta Giuseppe , Musolino Antonino 
Published: November 2023

BackgroundIt is possible to induce immunomodulation in HER2-positive breast cancer (BC) by modifying the route of administration of trastuzumab.MethodsIn this multicenter randomized phase II trial, all enrolled patients (pts) with T2–T4d HER2-positive BC received 3 cycles of neoadjuvant treatment (NAT) with fluorouracil, epirubicin and cyclophosphamide every 3 weeks (q21), followed by docetaxel/pertuzumab plus intravenous trastuzumab (arm A) or, docetaxel/pertuzumab plus subcutaneous (SC) trastuzumab (arm B) q21x4 cycles. After surgical operation, each pt was treated with trastuzumab q21x14 cycles using the same SC or intravenous formulation of NAT. Primary endpoint was the proportion of subjects with high stromal tumor-infiltrating lymphocytes (sTILs) in postneoadjuvant residual disease (RD).ResultsSixty-three pts (31 (arm A) and 32 (arm B)) were enrolled. Pathological complete response was obtained by 20/31 pts (64.5%; 95% CI 45.4% to 80.1%) in arm A and 19/32 pts (59.4%; 95% CI 40.1% to 76.3%) in arm B. High sTILs were observed in 27% and 46% of postneoadjuvant residual tumors in arms A and B, respectively. CD8+ T cells increased significantly in RDs of both arms (p=0.014 and 0.002 for arm A and B, respectively), whereas a significant decline in the level of CD4+ FoxP3+ regulatory T cells was observed only in arm B (p=0.016). A significant upregulation of PD-1 on sTILs was found in RD of pts enrolled in arm B (p=0.012), while programmed death-ligand 1 (PD-L1) was significantly overexpressed in residual tumors of arm A (p=0.02). A strong negative correlation was reported in arm B between expression of PD-L1 on pretreatment sTILs and CD3 expression on sTILs in RD (τ: −0.73). Grade≥3 AE incidence rates were similar between the two arms.ConclusionsSC trastuzumab induced relevant sTILs enrichment, with favorable variations of immune parameters in HER2-positive BC pts with RD after NAT. Novel immunotherapy strategies should be tested to achieve SC-specific, antitumor immune response.Trial registration numberNCT03144947, and EudraCT number: 2016-000435-41.
Assessment and predictive ability of the absolute neutrophil count in peripheral blood for in vivo CAR T cells expansion and CRS
Authors: Zhang Man , Long Xiaolu , Xiao Yi , Jin Jin , Chen Caixia , Meng Jiao , Liu Wanying , Liu Aichun , Chen Liting 
Published: November 2023

BackgroundChimeric antigen receptor (CAR) T cell therapy is an advanced and effective immunotherapy for relapsed or refractory B-cell malignancies. High expansion of CAR T cells in vivo and durable antitumor activity indicate a persistent therapeutic response. However, this treatment is linked to a high frequency of adverse events, such as cytokine release syndrome (CRS), which affects its efficacy and can even be life-threatening. At present, a variety of markers associated with clinical response and treatment toxicity after CAR T cells infusion have been reported. Although these biomarkers can act as effective indicators reflecting CAR T cells expansion as well as CRS, they fail to predict the expansion rate of CAR T cells. Hence, further investigation is urgent to find a new biomarker to fill this void.MethodsWe analyzed the association between the absolute neutrophil count (ANC) and CAR expansion and CRS in 45 patients with B-cell malignancies from two clinical trials. We proposed that ANC could be a practical biomarker for CAR T cells expansion and CRS, and conducted a feasibility analysis on its predictive ability.ResultsIn this study, 17 B-cell hematological malignancy patients with anti-B-cell maturation antigen CAR-treated and 28 with CAR19/22 T-cell-treated were enrolled and divided into an ANC-absence group and an ANC-presence group. The results showed that ANC absence correlated positively with CAR expansion and the expansion rate. The ANC can be used as a predictive marker for CAR T cells expansion. Moreover, the patients with ANC absence experienced a more severe CRS, and ANC performed a predictive ability for CRS. In addition, the peak serum concentration of several cytokines involved in CRS was higher in patients with ANC absence.ConclusionThus, we suggest ANC as an evaluative and predictive biomarker for CAR expansion and CRS during CAR T cell therapy, which can help to maximize clinical efficacy, reduce treatment-related toxicity and prolong survival.
Cardiovascular risk assessment in patients with antiphospholipid syndrome: a cross-sectional performance analysis of nine clinical risk prediction tools
Authors: Drosos George C , Konstantonis George , Sfikakis Petros P , Tektonidou Maria G 
Published: November 2023

ObjectivesThis study aimed to assess the performance of cardiovascular risk (CVR) prediction models reported by European Alliance of Associations for Rheumatology and European Society of Cardiology recommendations to identify high-atherosclerotic CVR (ASCVR) patients with antiphospholipid syndrome (APS).MethodsSix models predicting the risk of a first cardiovascular disease event (first-CVD) (Systematic Coronary Risk Evaluation (SCORE); modified-SCORE; Framingham risk score; Pooled Cohorts Risk Equation; Prospective Cardiovascular Münster calculator; Globorisk), three risk prediction models for patients with a history of prior arterial events (recurrent-CVD) (adjusted Global APS Score (aGAPSS); aGAPSSCVD; Secondary Manifestations of Arterial Disease (SMART)) and carotid/femoral artery vascular ultrasound (VUS) were used to assess ASCVR in 121 APS patients (mean age: 45.8±11.8 years; women: 68.6%). We cross-sectionally examined the calibration, discrimination and classification accuracy of all prediction models to identify high ASCVR due to VUS-detected atherosclerotic plaques, and risk reclassification of patients classified as non high-risk according to first-CVD/recurrent-CVD tools to actual high risk based on VUS.ResultsSpiegelhalter’s z-test p values 0.47–0.57, area under the receiver-operating characteristics curve (AUROC) 0.56–0.75 and Matthews correlation coefficient (MCC) 0.01–0.35 indicated moderate calibration, poor-to-acceptable discrimination and negligible-to-moderate classification accuracy, respectively, for all risk models. Among recurrent-CVD tools, SMART and aGAPSSCVD(for non-triple antiphospholipid antibody-positive patients) performed better (z/AUROC/MCC: 0.47/0.64/0.29 and 0.52/0.69/0.29, respectively) than aGAPSS. VUS reclassified 34.2%–47.9% and 40.5%–52.6% of patients classified as non-high-ASCVR by first-CVD and recurrent-CVD prediction models, respectively. In patients aged 40–54 years, >40% VUS-guided reclassification was observed for first-CVD risk tools and >50% for recurrent-CVD prediction models.ConclusionClinical CVR prediction tools underestimate actual high ASCVR in APS. VUS may help to improve CVR assessment and optimal risk factor management.
Vector—towards quantum key distribution with small satellites
Authors: Miller Alexander V. , Pismeniuk Liubov V. , Duplinsky Alexey V. , Merzlinkin Vitaly E. , Plukchi Aleksandr A. , Tikhonova Kseniia A. , Nesterov Ivan S. , Sevryukov Dmitry O. , Levashov Sergey D. , Fetisov Vladimir V. , Krasnopejev Sergei V. , Bakhshaliev Ruslan M. 
Published: November 2023

AbstractA satellite-constellation based global quantum network could allow secure quantum communication between remote users worldwide. Such a constellation could be formed of micro- or even nanosatellites, which have the advantage of being more cost-effective than larger expensive spacecrafts. At the same time, the features of quantum communication impose a number of technical requirements that are more difficult to meet when using small satellites. Full-fledged quantum communication has been demonstrated with neither a micro- nor a nanosatellite so far. The authors took up this challenge and have developed a 6U CubeSat weighting 9.5 kg. The satellite is to be launched in 2023 and has already successfully passed all the pre-flight tests. The mission is not yet intended for fully quantum communication. Nevertheless, the authors are testing such key functional elements as polarization reference-frame synchronization and acquisition, pointing and tracking system on it. Besides that, the payload accommodates a full-duplex telecommunication system operating at a bit rate of 50 Mbit/s: an up- and a downlink at wavelengths of 808 and 850 nm. After the satellite is launched, the main goal to be achieved is to demonstrate stable connection between it and an optical ground station and carry out multiple communication sessions. In quantum communication, generating secret keys from raw measurement data implies two-way exchange of significant amount of information and therefore availability of a classical communication channel with a high bandwidth is one of the crucial things. In the following mission, which envisages an overall quantum key distribution system, we plan to use the free-space optical link for such an exchange of data, whereas the RF link will only be used for telemetry and telecommand.
Data-driven Analysis of the Cost-Performance Trade-off of Reconfigurable Intelligent Surfaces in a Production Network
Authors: Rossanese Marco , Garcia-Saavedra Andres , Lutu Andra Elena , Costa Perez Xavier 
Published: November 2023

This paper presents a comprehensive study on the deployment of Reconfigurable Intelligent Surfaces (RIS) in urban environments with poor radio coverage. We focus on the city of London, a large metropolis where radio network planning presents unique challenges due to diverse geographical and structural features. Using crowd-sourced datasets, we analyze the Reference Signal Received Power (RSRP) from end-user devices to understand the existing radio coverage landscape of a major Mobile Network Operator (MNO). Our study identifies areas with poor coverage and proposes the deployment of RIS to enhance signal strength and coverage. We selected a set of potential sites for RIS deployment and, combining data from the MNO, data extracted from a real RIS prototype, and a ray-tracing tool, we analyzed the gains of this novel technology with respect to deploying more conventional technologies in terms of RSRP, coverage, and cost-efficiency.
To the best of our knowledge, this is the first data-driven analysis of the cost-efficiency of RIS technology in the production of urban networks. Our findings provide compelling evidence about the potential of RIS as a cost-efficient solution for enhancing radio coverage in complex urban mobile networks. More specifically, our results indicate that large-scale RIS technology, when applied in real-world urban mobile network scenarios, can achieve 72% of the coverage gains attainable by deploying additional cells with only 22% of their Total Cost of Ownership (TCO) over a 5-year timespan. Consequently, RIS technology offers around 3x higher cost-efficiency than other more conventional coverage-enhancing technologies.
Decline in the Incidence of Distant Recurrence of Breast Cancer: A Population-Based Health Record Linkage Study, Australia 2001–2016
Authors: Lord Sarah J. , Daniels Benjamin , O'Connell Dianne L. , Kiely Belinda E. , Beith Jane , Smith Andrea L. , Pearson Sallie-Anne , Chiew Kim-Lin , Bulsara Max K. , Houssami Nehmat 
Published: November 2023

Abstract

Background:
We investigated differences in cumulative incidence of first distant recurrence (DR) following non-metastatic breast cancer over a time period when new adjuvant therapies became available in Australia.

Methods:
We conducted a health record linkage study of females with localized (T1–3N0) or regional (T4 or N+) breast cancer in the New South Wales Cancer Registry in 2001 to 2002 and 2006 to 2007. We linked cancer registry records with administrative records from hospitals, dispensed medicines, radiotherapy services, and death registrations to estimate the 9-year cumulative incidence of DR and describe use of adjuvant treatment.

Results:
The study included 13,170 women (2001–2002 n = 6,338, 2006–2007 n = 6,832). The 9-year cumulative incidence of DR was 3.6% [95% confidence interval (CI), 2.3%–4.9%] lower for 2006–2007 diagnoses (15.0%) than 2001–2002 (18.6%). Differences in the annual hazard of DR between cohorts were largest in year two. DR incidence declined for localized and regional disease. Decline was largest for ages &lt;40 years (absolute difference, 14.4%; 95% CI, 8.3%–20.6%), whereas their use of adjuvant chemotherapy (2001–2002 49%, 2006–2007 75%) and HER2-targeted therapy (2001–2002 0%, 2006–2007 16%) increased. DR did not decline for ages ≥70 years (absolute difference, 0.9%; 95% CI, −3.6%–1.8%) who had low use of adjuvant chemotherapy and HER2-targeted therapy.

Conclusions:
This whole-of-population study suggests that DR incidence declined over time. Decline was largest for younger ages, coinciding with changes to adjuvant breast cancer therapy.

Impact:
Study findings support the need for trials addressing questions relevant to older people and cancer registry surveillance of DR to inform cancer control programs.
Modeling Molecular Pathogenesis of Idiopathic Pulmonary Fibrosis-Associated Lung Cancer in Mice
Authors: Barravecchia Ivana , Lee Jennifer M. , Manassa Jason , Magnuson Brian , Ferris Sarah F. , Cavanaugh Sophia , Steele Nina G. , Espinoza Carlos E. , Galban Craig J. , Ramnath Nithya , Frankel Timothy L. , Pasca di Magliano Marina , Galban Stefanie 
Published: November 2023

Abstract

Idiopathic pulmonary fibrosis (IPF) is characterized by progressive, often fatal loss of lung function due to overactive collagen production and tissue scarring. Patients with IPF have a sevenfold-increased risk of developing lung cancer. The COVID-19 pandemic has increased the number of patients with lung diseases, and infection can worsen prognoses for those with chronic lung diseases and disease-associated cancer. Understanding the molecular pathogenesis of IPF-associated lung cancer is imperative for identifying diagnostic biomarkers and targeted therapies that will facilitate prevention of IPF and progression to lung cancer. To understand how IPF-associated fibroblast activation, matrix remodeling, epithelial-to-mesenchymal transition (EMT), and immune modulation influences lung cancer predisposition, we developed a mouse model to recapitulate the molecular pathogenesis of pulmonary fibrosis–associated lung cancer using the bleomycin and Lewis lung carcinoma models. We demonstrate that development of pulmonary fibrosis–associated lung cancer is likely linked to increased abundance of tumor-associated macrophages and a unique gene signature that supports an immune-suppressive microenvironment through secreted factors. Not surprisingly, preexisting fibrosis provides a pre-metastatic niche and results in augmented tumor growth, and tumors associated with bleomycin-induced fibrosis are characterized by a dramatic loss of cytokeratin expression, indicative of EMT.

Implications:
This characterization of tumors associated with lung diseases provides new therapeutic targets that may aid in the development of treatment paradigms for lung cancer patients with preexisting pulmonary diseases.