bluuebunny/crossref_metadata_2025_split huggingface dataset:
Assessing the safety, tolerability and efficacy of PLGA-based immunomodulatory nanoparticles in patients with advanced NY-ESO-1-positive cancers: a first-in-human phase I open-label dose-escalation study protocol
Authors: Creemers Jeroen H A , Pawlitzky Inka , Grosios Konstantina , Gileadi Uzi , Middleton Mark R , Gerritsen Winald R , Mehra Niven , Rivoltini Licia , Walters Ian , Figdor Carl G , Ottevanger Petronella B , de Vries I Jolanda M 
Published: November 2021

IntroductionThe undiminished need for more effective cancer treatments stimulates the development of novel cancer immunotherapy candidates. The archetypical cancer immunotherapy would induce robust, targeted and long-lasting immune responses while simultaneously circumventing immunosuppression in the tumour microenvironment. For this purpose, we developed a novel immunomodulatory nanomedicine: PRECIOUS-01. As a PLGA-based nanocarrier, PRECIOUS-01 encapsulates a tumour antigen (NY-ESO-1) and an invariant natural killer T cell activator to target and augment specific antitumour immune responses in patients with NY-ESO-1-expressing advanced cancers.Methods and analysisThis open-label, first-in-human, phase I dose-escalation trial investigates the safety, tolerability and immune-modulatory activity of increasing doses of PRECIOUS-01 administered intravenously in subjects with advanced NY-ESO-1-expressing solid tumours. A total of 15 subjects will receive three intravenous infusions of PRECIOUS-01 at a 3-weekly interval in three dose-finding cohorts. The trial follows a 3+3 design for the dose-escalation steps to establish a maximum tolerated dose (MTD) and/or recommended phase II dose (RP2D). Depending on the toxicity, the two highest dosing cohorts will be extended to delineate the immune-related parameters as a readout for pharmacodynamics. Subjects will be monitored for safety and the occurrence of dose-limiting toxicities. If the MTD is not reached in the planned dose-escalation cohorts, the RP2D will be based on the observed safety and immune-modulatory activity as a pharmacodynamic parameter supporting the RP2D. The preliminary efficacy will be evaluated as an exploratory endpoint using the best overall response rate, according to Response Evaluation Criteria in Solid Tumors V.1.1.Ethics and disseminationThe Dutch competent authority (CCMO) reviewed the trial application and the medical research ethics committee (CMO Arnhem-Nijmegen) approved the trial under registration number NL72876.000.20. The results will be disseminated via (inter)national conferences and submitted for publication to a peer-reviewed journal.Trial registration numberNCT04751786.
Evaluation of the effects of high-level laser and electrocautery in lingual frenectomy surgeries in infants: protocol for a blinded randomised controlled clinical trial
Authors: Mazzoni Adriana , Navarro Ricardo Scarparo , Fernandes Kristianne Porta Santos , Horliana Anna Carolina Ratto Tempestini , Mesquita-Ferrari Raquel Agnelli , Motta Pamella Barros , Silva Tamiris , Gomes Andréa Oliver , Martimbianco Ana Luiza Cabrera , Sobral Ana Paula Taboada , Santos Elaine Marcilio , Motta Lara Jansiski , Bussadori Sandra Kalil 
Published: November 2021

IntroductionAnkyloglossia (tongue-tie) is an anomaly characterised by an abnormally short, thick or small lingual frenulum that restricts tongue movements. This condition is considered one of the factors that can interfere with breast feeding by diminishing the ability of the newborn to latch adequately. According to the Brazilian Health Ministry, the prevalence of this anomaly among newborns is 3%–16%. Frenectomy is the most suitable surgical procedure for the treatment of ankyloglossia. The aim of this study is to compare the performance of electrocautery and high-power diode laser as forms of frenectomy.Methods and analysisThe proposed study will be a randomised, controlled, blind clinical trial involving the participation of healthy infants 0–3 months of age with breastfeeding difficulty and a diagnosis of tongue-tie with an indication for lingual frenectomy. The guardians will receive clarifications regarding the procedures and will authorise the participation of the infants by signing a statement of informed consent. A non-blinded researcher will perform the screening and procedures and a blinded researcher will perform the postoperative evaluations. Fifty-six infants will be randomly allocated into two groups (n=28): the electrocautery group or the high-power laser group. The preparation of the patients, asepsis and infection control procedures will rigorously follow biosafety norms. For both groups, patient histories will be taken, clinical evaluations will be performed and a standardised photograph of the lingual frenulum will be taken before surgery. The Bristol Tongue Assessment Tool will be used. We will evaluate pain in the mother during breast feeding before, immediately after, and 15 days after surgery.Ethics and disseminationThis protocol was submitted to the Research Ethics Committee of Nove de Julho University, having been given a favourable opinion (Number: 4387769). Results will be submitted to international peer-reviewed journals and presented at international conferences.Trial registration numberNCT04487418.
Outcomes after perioperative SARS-CoV-2 infection in patients with proximal femoral fractures: an international cohort study
Authors:   COVIDSurg Collaborative
Published: November 2021

ObjectivesStudies have demonstrated high rates of mortality in people with proximal femoral fracture and SARS-CoV-2, but there is limited published data on the factors that influence mortality for clinicians to make informed treatment decisions. This study aims to report the 30-day mortality associated with perioperative infection of patients undergoing surgery for proximal femoral fractures and to examine the factors that influence mortality in a multivariate analysis.SettingProspective, international, multicentre, observational cohort study.ParticipantsPatients undergoing any operation for a proximal femoral fracture from 1 February to 30 April 2020 and with perioperative SARS-CoV-2 infection (either 7 days prior or 30-day postoperative).Primary outcome30-day mortality. Multivariate modelling was performed to identify factors associated with 30-day mortality.ResultsThis study reports included 1063 patients from 174 hospitals in 19 countries. Overall 30-day mortality was 29.4% (313/1063). In an adjusted model, 30-day mortality was associated with male gender (OR 2.29, 95% CI 1.68 to 3.13, p<0.001), age >80 years (OR 1.60, 95% CI 1.1 to 2.31, p=0.013), preoperative diagnosis of dementia (OR 1.57, 95% CI 1.15 to 2.16, p=0.005), kidney disease (OR 1.73, 95% CI 1.18 to 2.55, p=0.005) and congestive heart failure (OR 1.62, 95% CI 1.06 to 2.48, p=0.025). Mortality at 30 days was lower in patients with a preoperative diagnosis of SARS-CoV-2 (OR 0.6, 95% CI 0.6 (0.42 to 0.85), p=0.004). There was no difference in mortality in patients with an increase to delay in surgery (p=0.220) or type of anaesthetic given (p=0.787).ConclusionsPatients undergoing surgery for a proximal femoral fracture with a perioperative infection of SARS-CoV-2 have a high rate of mortality. This study would support the need for providing these patients with individualised medical and anaesthetic care, including medical optimisation before theatre. Careful preoperative counselling is needed for those with a proximal femoral fracture and SARS-CoV-2, especially those in the highest risk groups.Trial registration numberNCT04323644
Best-BRA (Is subpectoral or prepectoral implant placement best in immediate breast reconstruction?): a protocol for a pilot randomised controlled trial of subpectoral versus prepectoral immediate implant-based breast reconstruction in women following mastectomy
Authors: Roberts Kirsty , Mills Nicola , Metcalfe Chris , Lane Athene , Clement Clare , Hollingworth William , Taylor Jodi , Holcombe Chris , Skillman Joanna , Fairhurst Katherine , Whisker Lisa , Cutress Ramsey , Thrush Steven , Fairbrother Patricia , Potter Shelley 
Published: November 2021

BackgroundImplant-based breast reconstruction (IBBR) is the most commonly performed reconstructive procedure following mastectomy. IBBR techniques are evolving rapidly, with mesh-assisted subpectoral reconstruction becoming the standard of care and more recently, prepectoral techniques being introduced. These muscle-sparing techniques may reduce postoperative pain, avoid implant animation and improve cosmetic outcomes and have been widely adopted into practice. Although small observational studies have failed to demonstrate any differences in the clinical or patient-reported outcomes of prepectoral or subpectoral reconstruction, high-quality comparative evidence of clinical or cost-effectiveness is lacking. A well-designed, adequately powered randomised controlled trial (RCT) is needed to compare the techniques, but breast reconstruction RCTs are challenging. We, therefore, aim to undertake an external pilot RCT (Best-BRA) with an embedded QuinteT Recruitment Intervention (QRI) to determine the feasibility of undertaking a trial comparing prepectoral and subpectoral techniques.Methods and analysisBest-BRA is a pragmatic, two-arm, external pilot RCT with an embedded QRI and economic scoping for resource use. Women who require a mastectomy for either breast cancer or risk reduction, elect to have an IBBR and are considered suitable for both prepectoral and subpectoral reconstruction will be recruited and randomised 1:1 between the techniques.The QRI will be implemented in two phases: phase 1, in which sources of recruitment difficulties are rapidly investigated to inform the delivery in phase 2 of tailored interventions to optimise recruitment of patients.Primary outcomes will be (1) recruitment of patients, (2) adherence to trial allocation and (3) outcome completion rates. Outcomes will be reviewed at 12 months to determine the feasibility of a definitive trial.Ethics and disseminationThe study has been approved by the National Health Service (NHS) Wales REC 6 (20/WA/0338). Findings will be presented at conferences and in peer-reviewed journals.Trial registration numberISRCTN10081873.
Evaluating the role of orange juice, HESPERidin in vascular HEALTH benefits (HESPER-HEALTH study): protocol for a randomised controlled trial
Authors: Verny Marie-Anne , Milenkovic Dragan , Macian Nicolas , Pereira Bruno , Evrard Rémy , Gilcher Caroline , Steingass Christof B , Mosoni Pascale , Gladine Cécile , Monfoulet Laurent-Emmanuel , Schweiggert Ralf , Pickering Gisèle , Morand Christine 
Published: November 2021

IntroductionAlthough epidemiological studies associate the consumption of sugary beverages with adverse health effects, human experimental studies have demonstrated substantially different metabolic responses when 100% fruit juices are compared with artificial beverages. Fruit juices do not just provide sugars and associated calories, but they are also rich in bioactive compounds. Flavanones are bioactives specifically and abundantly found in citrus foods, with hesperidin as the major representative in sweet oranges. Flavanone intake has been associated with a lower incidence of mortality from cardiovascular disease (CVD). However, clinical evidence are too scarce to confirm the vasculoprotective effects of 100% orange juice (OJ) presumably mediated by flavanones and thereby do not allow firm conclusions to be drawn about their efficacy.Methods and analysisThe HESPER-HEALTH study aims to assess the efficacy of OJ in improving vascular function and the contribution of hesperidin to these effects. This double-blind, randomised, controlled, crossover study will be carried out in 42 volunteers predisposed to CVD, based on age and on overweight. It includes three 6-week periods of consumption of 330 mL/d of OJ versus control drinks with and without hesperidin at a dose in agreement with a daily OJ serving (approx. 200–215 mg). The primary outcome is endothelial function, assessed by flow mediated dilation, with measurements performed at fasting and postprandially in response to a challenge meal. The secondary outcomes include bioavailability and metabolism of flavanones, changes in other markers of vascular function, systemic biomarkers of cardiovascular risk, endothelial dysfunction and inflammation, vitamin C and carotenoids status, anthropometry and body composition, gut microbiota composition, nutrigenomic response and in oxylipin profiling.Ethics and disseminationThis ongoing study was approved by the Ethics committee Sud-Est III, Bron, France on 17 November 2020. The trial is registered on ClinicalTrials.gov. The results will be disseminated in peer-reviewed journals.Trial registration numberNCT04731987; Pre-results.
A risk-adjusted and anatomically stratified cohort comparison study of open surgery, endovascular techniques and medical management for juxtarenal aortic aneurysms—the UK COMPlex AneurySm Study (UK-COMPASS): a study protocol
Authors: Patel Shaneel R , Ormesher David C , Smith Samuel R , Wong Kitty H F , Bevis Paul , Bicknell Colin D , Boyle Jonathan R , Brennan John A , Campbell Bruce , Cook Andrew , Crosher Alastair P , Duarte Rui V , Flett Murray M , Gamble Carrol , Jackson Richard J , Juszczak Maciej T , Loftus Ian M , Nordon Ian M , Patel Jai V , Platt Kellie , Psarelli Eftychia-Eirini , Rowlands Peter C , Smyth John V , Spachos Theodoros , Taggart Leigh , Taylor Claire , Vallabhaneni Srinivasa Rao 
Published: November 2021

IntroductionIn one-third of all abdominal aortic aneurysms (AAAs), the aneurysm neck is short (juxtarenal) or shows other adverse anatomical features rendering operations more complex, hazardous and expensive. Surgical options include open surgical repair and endovascular aneurysm repair (EVAR) techniques including fenestrated EVAR, EVAR with adjuncts (chimneys/endoanchors) and off-label standard EVAR. The aim of the UK COMPlex AneurySm Study (UK-COMPASS) is to answer the research question identified by the National Institute for Health Research Health Technology Assessment (NIHR HTA) Programme: ‘What is the clinical and cost-effectiveness of strategies for the management of juxtarenal AAA, including fenestrated endovascular repair?’Methods and analysisUK-COMPASS is a cohort study comparing clinical and cost-effectiveness of different strategies used to manage complex AAAs with stratification of physiological fitness and anatomical complexity, with statistical correction for baseline risk and indication biases. There are two data streams. First, a stream of routinely collected data from Hospital Episode Statistics and National Vascular Registry (NVR). Preoperative CT scans of all patients who underwent elective AAA repair in England between 1 November 2017 and 31 October 2019 are subjected to Corelab analysis to accurately identify and include every complex aneurysm treated. Second, a site-reported data stream regarding quality of life and treatment costs from prospectively recruited patients across England. Site recruitment also includes patients with complex aneurysms larger than 55 mm diameter in whom an operation is deferred (medical management). The primary outcome measure is perioperative all-cause mortality. Follow-up will be to a median of 5 years.Ethics and disseminationThe study has received full regulatory approvals from a Research Ethics Committee, the Confidentiality Advisory Group and the Health Research Authority. Data sharing agreements are in place with National Health Service Digital and the NVR. Dissemination will be via NIHR HTA reporting, peer-reviewed journals and conferences.Trial registration numberISRCTN85731188.
Predictors of relapse in MOG antibody associated disease: a cohort study
Authors: Huda Saif , Whittam Daniel , Jackson Richard , Karthikeayan Venkatraman , Kelly Patricia , Linaker Sam , Mutch Kerry , Kneen Rachel , Woodhall Mark , Murray Katy , Hunt David , Waters Patrick , Jacob Anu 
Published: November 2021

ObjectiveTo identify factors predictive of relapse risk and disability in myelin oligodendrocyte glycoprotein associated disease (MOGAD).SettingPatients were seen by the neuromyelitis optica spectrum disorders (NMOSD) service in Liverpool, UK, a national referral centre for adult patients with MOGAD, NMOSD and related conditions.ParticipantsPatients with MOGAD=76 from England, Northern Ireland and Scotland were included in this cohort study.ResultsRelapsing disease was observed in 55% (42/76) of cases. Steroid treatment>1 month (OR 0.2, 95% CI 0.05 to 0.80; p=0.022), transverse myelitis (TM) at first attack (OR 0.03, 95% CI 0.004 to 0.23; p=0.001) and male sex (OR 0.16, 95% CI 0.04 to 0.68; p=0.014) were associated with monophasic disease (area under the curve=0.85). Male sex (HR 0.46, 95% CI 0.24 to 0.89; p=0.011) and TM at disease onset (HR 0.42, 95% CI 0.22 to 0.82; p=0.011) were also associated with an increased latency to first relapse. 45% (32/71) of patients became MOG-antibody negative and in relapsing patients negative seroconversion was associated with a lower relapse risk (relative risk 0.11 95% CI 0.05 to 0.26; p<0.001). No specific factors were predictive of visual or overall disability.ConclusionsMale patients with spinal cord involvement at disease onset have a lower risk of relapsing disease and longer latency to first relapse. Steroid treatment for at least 1 month at first attack was also associated with a monophasic disease course. MOG-antibody negative seroconversion was associated with a lower risk of relapse and may help inform treatment decisions and duration.
A qualitative study of abortion care providers’ perspectives on telemedicine medical abortion provision in the context of COVID-19
Authors: Reynolds-Wright John Joseph , Boydell Nicola , Cameron Sharon , Harden Jeni 
Published: November 2021

BackgroundTelemedicine for medical abortion care was rapidly introduced in Great Britain in response to the COVID-19 pandemic. A growing body of literature demonstrates that telemedicine abortion care is safe, effective and highly acceptable to patients. Less is known about the perspectives of abortion care providers (ACPs).MethodsQualitative research within the telemedicine abortion service in Lothian (Edinburgh and surrounding region), UK. We conducted qualitative in-depth interviews with ACPs between May and July 2020 (doctors, n=6; nurses, n=10) and analysed the data thematically.ResultsWe present three themes from our qualitative analysis: (1) Selective use of ultrasound – the move away from routine ultrasound for determination of gestational age was generally viewed positively. Initial anxiety about non-detection of ectopic pregnancy and later gestations was expressed by some ACPs, but concerns were addressed through clinical practice and support structures within the clinic. (2) Identifying safeguarding issues – in the absence of visual cues some ACPs reported concerns about their ability to identify safeguarding issues, specifically domestic violence. Conversely it was acknowledged that teleconsultations may improve detection of this in some situations. (3) Provision of information during the consultation – telephone consultations were considered more focused than in-person consultations and formed only part of the overall ‘package’ of information provided to patients, supplemented by online and written information.ConclusionsACPs providing telemedicine abortion care value this option for patients and believe it should remain beyond the COVID-19 pandemic. Safeguarding patients and the selective use of ultrasound can be initially challenging; however, with experience, staff confidence improves.
Scaling behaviors of heavy flavor meson suppression and flow in different nuclear collision systems at the LHC
Authors: Li Shu-Qing , Xing Wen-Jing , Wu Xiang-Yu , Cao Shanshan , Qin Guang-You 
Published: November 2021

AbstractWe explore the system size dependence of heavy-quark-QGP interaction by studying the heavy flavor meson suppression and elliptic flow in Pb–Pb, Xe–Xe, Ar–Ar and O–O collisions at the LHC. The space-time evolution of the QGP is simulated using a $$(3+1)$$

(
3
+
1
)

-dimensional viscous hydrodynamic model, while the heavy-quark-QGP interaction is described by an improved Langevin approach that includes both collisional and radiative energy loss inside a thermal medium. Within this framework, we provides a reasonable description of the D meson suppression and flow coefficients in Pb–Pb collisions, as well as predictions for both D and B meson observables in other collision systems yet to be measured. We find a clear hierarchy for the heavy meson suppression with respect to the size of the colliding nuclei, while their elliptic flow coefficient relies on both the system size and the geometric anisotropy of the QGP. Sizable suppression and flow are predicted for both D and B mesons in O–O collisions, which serve as a crucial bridge of jet quenching between large and small collision systems. Scaling behaviors between different collision systems are shown for heavy meson suppression factor and the bulk-eccentricity-rescaled heavy meson elliptic flow as functions of the number of participant nucleons in heavy-ion collisions.
Revisiting the role of CP-conserving processes in cosmological particle–antiparticle asymmetries
Authors: Ghosh Avirup , Ghosh Deep , Mukhopadhyay Satyanarayan 
Published: November 2021

AbstractWe point out qualitatively different possibilities on the role of CP-conserving processes in generating cosmological particle–antiparticle asymmetries, with illustrative examples from models in leptogenesis and asymmetric dark matter production. In particular, we consider scenarios in which the CP-violating and CP-conserving processes are either both decays or both scatterings, thereby being naturally of comparable rates. This is in contrast to the previously considered CP-conserving processes in models of leptogenesis in different see-saw mechanisms, in which the CP-conserving scatterings typically have lower rates compared to the CP-violating decays, due to a Boltzmann suppression. We further point out that the CP-conserving processes can play a dual role if the asymmetry is generated in the mother sector itself, in contrast to the conventional scenarios in which it is generated in the daughter sector. This is because, the CP-conserving processes initially suppress the asymmetry generation by controlling the out-of-equilibrium number densities of the bath particles, but subsequently modify the ratio of particle antiparticle yields at the present epoch by eliminating the symmetric component of the bath particles through pair-annihilations, leading to a competing effect stemming from the same process at different epochs. We find that the asymmetric yields for relevant particle–antiparticle systems can vary by orders of magnitude depending upon the relative size of the CP-conserving and violating reaction rates.