bluuebunny/crossref_metadata_2025_split huggingface dataset:
Intensive care with extracorporeal membrane oxygenation rewarming in accident severe hypothermia (ICE-CRASH) study: a protocol for a multicentre prospective, observational study in Japan
Authors: Takauji Shuhei , Hayakawa Mineji 
Published: October 2021

IntroductionAccidental hypothermia (AH) is a rare but critical disease, leading to death in severe cases. In recent decades, extracorporeal membrane oxygenation (ECMO) has been successfully used to rewarm hypothermic patients with cardiac arrest or circulation instability. However, data on the efficacy of rewarming using ECMO for patients with AH are limited. Therefore, a large-scale, multicentre, prospective study is warranted. The primary objective of this study will be to clarify the effectiveness of rewarming using ECMO for patients with AH. Our secondary objectives will be to compare the incidence of adverse effects between ECMO rewarming and non-ECMO rewarming and to identify the most appropriate management of ECMO for AH.Methods and analysesThe Intensive Care with ExtraCorporeal membrane oxygenation Rewarming in Accidentally Severe Hypothermia study is taking place in 35 tertiary emergency medical facilities in Japan. The inclusion criteria are patients ≥18 years old with a body temperature ≤32°C. We will include patients with AH who present to the emergency department from December 2019 to March 2022. The research personnel at each hospital will collect several variables, including patient demographics, rewarming method, ECMO data and complications. Our primary outcome is to compare the 28-day survival rate between the ECMO and non-ECMO (other treatments) groups among patients with severe AH. Our secondary outcomes are to compare the following values between the ECMO and non-ECMO groups: length of stay in the intensive-care unit and complications. Furthermore, in patients with cardiac arrest, the Cerebral Performance Category score at discharge will be compared between both groups.Ethics and disseminationThis study received research ethics approval from Asahikawa Medical University (18194 and 19115). The study was approved by the institutional review board of each hospital, and the requirement for informed consent was waived due to the observational nature of the study.Trial registration numberUMIN000036132.
Protocol of BRICS: Brazilian multicentric pragmatic randomised trial of surgical interventions for displaced diaphyseal clavicle fracture study: MIPO versus ORIF for the treatment of displaced midshaft clavicle fractures
Authors: Mendes Jr. Adriano Fernando , Curado Rodrigo Fleury , Dias Jr. Jair Moreira , Mota Neto José Da , Carrazzone Oreste Lemos , Pagan Alexandre Rosa , Labronici Pedro José , Labronici Gustavo José , Goes Matheus Pires De Araújo , Mouraria Guilherme Grisi , Zogbi Daniel Romano , Brigatto Rafael Mulatti , Uehara Anderson , Parro Otávio Costa , Hisano Fernando Mitsuo , Teixeira Bruno De Souza , Silva Rafael Waldolato , Lazarini Rafael Fuchs , Godinho André Couto , Godinho Pedro Couto , França Flavio De Oliveira , Godinho Glaydson Gomes , Freitas José Marcio Alves , Mariosa Carlos Alberto Menezes , Souza Bruno Gonçalves Schröder e , De Oliveira Valdeci Manoel , De Simoni Leandro Furtado , Pereira Camila Corrêa , Antunes Filho Jurandir , Matsunaga Fabio Teruo , Belloti João Carlos , Tamaoki Marcel Jun Sugawara 
Published: October 2021

IntroductionFractures of the diaphysis of the clavicle are common; however, treatment guidelines for this condition are lacking. Surgery is associated with a lower risk of non-union and better functional outcomes but a higher risk of complications. Open reduction and internal fixation with plates and screws are the most commonly performed techniques, but they are associated with paraesthesia in the areas of incisions, extensive surgical exposure and high rates of implant removal. Minimally invasive techniques for treating these fractures have a lower rate of complications. The aim of this study is to evaluate which surgical treatment option (minimally invasive osteosynthesis or open reduction and internal fixation) has better prognosis in terms of complications and reoperations.Methods and analysisThe study proposed is a multicentric, pragmatic, randomised, open-label, superiority clinical trial between minimally invasive osteosynthesis and open reduction and internal fixation for surgical treatment of patients with displaced fractures of the clavicle shaft. In the proposed study, 190 individuals with displaced midshaft clavicle fractures, who require surgery as treatment, will be randomised. The assessment will occur at 2, 6, 12, 24 and 48 weeks, respectively. The primary outcome of the study will be the number of complications and reoperations. For sample size calculation, a moderate effective size between the techniques was considered in a two-tailed test, with 95% confidence and 90% power. Complications include cases of infection, hypertrophic scarring, non-union, refracture, implant failure, hypoesthesia, skin irritation and shoulder pain. Reoperations are defined as the number of surgeries for pseudoarthrosis, implant failure, infection and elective removal of the implant.Ethics and disseminationStudy approved by the institutional ethics committee (number 34249120.9.0000.5505—V.3). The results will be disseminated by publications in peer-reviewed journals and presentations in medical meetings.Trial registration numberRBR-3czz68)/UTN U1111-1257-8953.
Study protocol: a pilot randomised waitlist-controlled trial of a dyadic mobile health intervention for black sexual-minority male couples with HIV in the USA
Authors: Kim Hyunjin Cindy , Pollack Lance M , Saberi Parya , Neilands Torsten B , Arnold Emily A , Bright Darius Jovon , Williams Robert W , Kegeles Susan M , Tan Judy Y 
Published: October 2021

IntroductionHIV care engagement is lower among black sexual-minority men relative to other racial/ethnic groups of sexual-minority men. Being in a primary relationship is generally associated with more successful HIV care engagement across various populations. However, among black sexual-minority men, the association between primary relationship status and HIV-related outcomes is inconsistent across the HIV care continuum. Given the ubiquity of mobile technology access and use among racial/ethnic minority communities, leveraging mobile technology for HIV care engagement appears a promising intervention strategy. This paper outlines the protocol of the LetSync study, a pilot randomised controlled trial of a mobile health app intervention developed using the Framework of Dyadic HIV Care Engagement to improve care-engagement outcomes among black sexual-minority male couples living with HIV.Methods and analysisEighty black sexual-minority men in couples (n=160) will be enrolled to pilot test the LetSync app. At least one member of each dyad must be both HIV-positive and self-identify as black/African-American. Couples will be randomised to either a waitlist-control arm or an intervention that uses relationship-based approach to improve HIV care engagement. We will assess feasibility and acceptability of trial procedures and intervention protocols based on predefined metrics of feasibility and acceptability. Execution of the study will yield the opportunity to conduct analyses to test the measurement and analysis protocol on antiretroviral therapy adherence by comparing the intervention and waitlist-control arms on self-reported and biological (hair sample) measures of adherence.Ethics and disseminationStudy staff will obtain electronic consent from all participants. This study has been approved by the University of California (UCSF) Institutional Review Board. Study staff will work with the Community Advisory Board at the UCSF Center for AIDS Prevention Studies Board to disseminate results to participants and the community via open discussions, presentations, journal publications and/or social media.Trial registration numberNCT04951544.
Peptide vaccine targeting mutatedGNAS: a potential novel treatment for pseudomyxoma peritonei
Authors: Flatmark Kjersti , Torgunrud Annette , Fleten Karianne G , Davidson Ben , Juul Hedvig V , Mensali Nadia , Lund-Andersen Christin , Inderberg Else Marit 
Published: October 2021

BackgroundPseudomyxoma peritonei (PMP) is a rare, slow-growing abdominal cancer with no efficacious treatment options in non-resectable and recurrent cases. Otherwise, rare activating mutations in theGNASoncogene are remarkably frequent in PMP and the mutated gene product, guanine nucleotide-binding protein α subunit (Gsα), is a potential tumor neoantigen, presenting an opportunity for targeting by a therapeutic cancer vaccine.MethodsTumor and blood samples were collected from 25 patients undergoing surgery for PMP (NCT02073500).GNASmutation analysis was performed by next-generation targeted sequencing or digital droplet PCR. Responses to stimulation with Gsα mutated (point mutations R201H and R201C) 30 mer peptides were analyzed in peripheral blood T cells derived from patients with PMP and healthy donors. Fresh PMP tumor samples were analyzed by mass cytometry using a panel of 35 extracellular markers, and cellular subpopulations were clustered and visualized using the visual stochastic network embedding analysis tool.ResultsGNASmutations were detected in 22/25 tumor samples (88%; R201H and R201C mutations detected in 16 and 6 cases, respectively). Strong T cell proliferation against Gsα mutated peptides was observed in 18/24 patients with PMP. Mass cytometry analysis of tumor revealed infiltration of CD3 +T cells in most samples, with variable CD4+:CD8 + ratios. A large proportion of T cells expressed immune checkpoint molecules, in particular programmed death receptor-1 and T cell immunoreceptor with Ig and ITIM, indicating that these T cells were antigen experienced.ConclusionThese findings point to the existence of a pre-existing immunity in patients with PMP towards mutated Gsα, which has been insufficient to control tumor growth, possibly because of inhibition of antitumor T cells by upregulation of immune checkpoint molecules. The results form a rationale for exploring peptide vaccination with Gsα peptides in combination with immune checkpoint inhibiton as a possible curative treatment for PMP and otherGNASmutated cancers.
Primary vulvar squamous cell carcinomas with high T cell infiltration and active immune signaling are potential candidates for neoadjuvant PD-1/PD-L1 immunotherapy
Authors: Kortekaas Kim E , Santegoets Saskia J , Tas Liselotte , Ehsan Ilina , Charoentong Pornpimol , van Doorn Helena C , van Poelgeest Mariette I E , Mustafa Dana A M , van der Burg Sjoerd H 
Published: October 2021

BackgroundA profound insight into the immune landscape of vulvar squamous cell carcinoma (VSCC) is lacking. Here, an in-depth interrogation of T cell infiltration, local immune contexture, signaling pathways and checkpoint molecule expression was performed in early-stage and late-stage VSCC.MethodsThe type, location, and infiltration pattern of T cells were studied in 109 patients with primary VSCC FIGO stage I–III. RNA expression of genes involved in immune oncology and oncogenic signaling pathways was analyzed in 40 VSCC, matched for prognostic clinicopathological variables, analyzed for HPV and p53 status, and selected based on T cell infiltration.ResultsHigh intraepithelial infiltration with CD4 or CD8 T cells was associated with longer overall and recurrence-free survival and formed an independent prognostic factor, outperforming molecular subtype and stage of the disease. Strong T cell infiltrated VSCC displayed a coordinated immune response reflected by a positive association between T cells and different lymphocyte and myeloid cell subsets. The expression of genes involved in the migration of T cells and myeloid cells, T cell activation and costimulation, interferon (IFN)-γ signaling, cytotoxicity and apoptosis was higher than in low infiltrated tumors. An active immune signaling profile was observed in all inflamed, part of the altered-excluded and not in altered-immunosuppressed or deserted VSCC. While several checkpoint molecules were overexpressed, only PD-L1 expression displayed discriminatory ability and clinical usefulness. High PD-L1 expression was detected in all inflamed and ~60% of the altered-excluded VSCC.ConclusionAn active immune signaling profile is present in 35% of primary FIGO I–III VSCCs, suggesting potential responsiveness to neoadjuvant PD-1/PD-L1 immunotherapy.
Predictors of incomplete aneurysm occlusion after treatment with the Pipeline Embolization Device: PREMIER trial 1 year analysis
Authors: Hanel Ricardo A , Monteiro Andre , Nelson Peter K , Lopes Demetrius K , Kallmes David F 
Published: October 2021

BackgroundFlow diverters have revolutionized the treatment of intracranial aneurysms. Nevertheless, some aneurysms fail to occlude with flow diversion. The Prospective Study on Embolization of Intracranial Aneurysms with the Pipeline Device (PREMIER) was a prospective, multicenter and single-arm trial of small and medium wide-necked unruptured aneurysms. In the current study, we evaluate the predictors of treatment failure in the PREMIER cohort.MethodsWe analyzed PREMIER patients who had incomplete occlusion (Raymond-Roy >1) at 1 year angiographic follow-up and compared them with those who achieved Raymond-Roy 1, aiming to identify predictors of treatment failure.Results25 aneurysms demonstrated incomplete occlusion at 1 year. There was a median reduction of 0.9 mm (IQR 0.41–2.43) in maximum diameter between pre-procedure and 1 year measurements, with no aneurysmal hemorrhage. Patients with incomplete occlusion were significantly older than those with complete occlusion (p=0.011). Smoking (p=0.045) and C6 segment location (p=0.005) were significantly associated with complete occlusion, while location at V4 (p=0.01) and C7 (p=0.007) and involvement of a side branch (p<0.001) were significantly associated with incomplete occlusion. In multivariable logistic regression, significant predictors of incomplete occlusion were non-smoker status (adjusted OR 4.49, 95% CI 1.11 to 18.09; p=0.03) and side branch involvement (adjusted OR 11.68, 95% CI 3.84 to 35.50; p<0.0001), while C6 location had reduced odds of incomplete occlusion (adjusted OR 0.29, 95% CI 0.10 to 0.84; p=0.02).ConclusionsThe results of our study are consistent with previous retrospective series and warrant consideration for technique adaptations to achieve higher occlusion rates. Further follow-up is needed to assess progression of aneurysm occlusion and clinical behavior in these cases.
Work functioning among young adults: the role of mental health problems from childhood to young adulthood
Authors: de Groot Samira , Veldman Karin , Amick III Benjamin C , Bültmann Ute 
Published: October 2021

ObjectivesMental health problems (MHPs) during childhood and adolescence are negatively associated with having a paid job in young adulthood. Yet, little is known about how young adults function at work, that is, do they experience difficulties in meeting their job demands given their health state. This longitudinal study aims to examine the impact of MHPs from childhood to young adulthood on young adults’ work functioning (WF).MethodsData were used from 1004 participants in the TRacking Adolescents’ Individual Lives Survey, a Dutch prospective cohort study with 18-year follow-up. MHP trajectories, including 11, 13.5, 16, 19, 22 and 26 age points, were identified using growth mixture models. WF was assessed at age 29 with the Work Role Functioning Questionnaire 2.0 (WRFQ). Regression analyses were conducted to examine the association between MHP trajectories and WF.ResultsYoung adults with high-stable trajectories of internalising and externalising problems reported lower WF (mean WRFQ scores of 70.5 and 70.7, respectively) than those with low-stable trajectories (78.4 and 77.2), that is, they experience difficulties in meeting the work demands for more than one work day per full-time work week. Young adults with moderate-stable or decreasing MHP trajectories reported lower WF scores compared with those with low-stable trajectories.ConclusionsBoth persistent high and elevated levels of MHPs from childhood to young adulthood are associated with lower WF scores in young adulthood compared with low-level MHPs. Occupational healthcare professionals should support young workers with a history of MHPs to optimise their work functioning.
Multi-Tier Stack of Block Chain with Proxy Re-Encryption Method Scheme on the Internet of Things Platform
Authors: Rawal Bharat S. , M. Poongodi , Manogaran Gunasekaran , Hamdi Mounir 
Published: October 2021

Block chain provides an innovative solution to information storage, transaction execution, security, and trust building in an open environment. The block chain is technological progress for cyber security and cryptography, with efficiency-related cases varying in smart grids, smart contracts, over the IoT, etc. The movement to exchange data on a server has massively increased with the introduction of the Internet of Things. Hence, in this research, Splitting of proxy re-encryption method (Split-PRE) has been suggested based on the IoT to improve security and privacy in a private block chain. This study proposes a block chain-based proxy re-encryption program to resolve both the trust and scalability problems and to simplify the transactions. After encryption, the system saves the Internet of Things data in a distributed cloud. The framework offers dynamic, smart contracts between the sensor and the device user without the intervention of a trustworthy third party to exchange the captured IoT data. It uses an efficient proxy re-encryption system, which provides the owner and the person existing in the smart contract to see the data. The experimental outcomes show that the proposed approach enhances the efficiency, security, privacy, and feasibility of the system when compared to other existing methods.
Gene-Level Germline Contributions to Clinical Risk of Recurrence Scores in Black and White Patients with Breast Cancer
Authors: Patel Achal , García-Closas Montserrat , Olshan Andrew F. , Perou Charles M. , Troester Melissa A. , Love Michael I. , Bhattacharya Arjun 
Published: October 2021

AbstractContinuous risk of recurrence scores (CRS) based on tumor gene expression are vital prognostic tools for breast cancer. Studies have shown that Black women (BW) have higher CRS than White women (WW). Although systemic injustices contribute substantially to breast cancer disparities, evidence of biological and germline contributions is emerging. In this study, we investigated germline genetic associations with CRS and CRS disparity using approaches modeled after transcriptome-wide association studies (TWAS). In the Carolina Breast Cancer Study, using race-specific predictive models of tumor expression from germline genetics, we performed race-stratified (N = 1,043 WW, 1,083 BW) linear regressions of three CRS (ROR-S: PAM50 subtype score; proliferation score; ROR-P: ROR-S plus proliferation score) on imputed tumor genetically regulated tumor expression (GReX). Bayesian multivariate regression and adaptive shrinkage tested GReX-prioritized genes for associations with tumor PAM50 expression and subtype to elucidate patterns of germline regulation underlying GReX-CRS associations. At FDR-adjusted P &lt; 0.10, 7 and 1 GReX prioritized genes among WW and BW, respectively. Among WW, CRS were positively associated with MCM10, FAM64A, CCNB2, and MMP1 GReX and negatively associated with VAV3, PCSK6, and GNG11 GReX. Among BW, higher MMP1 GReX predicted lower proliferation score and ROR-P. GReX-prioritized gene and PAM50 tumor expression associations highlighted potential mechanisms for GReX-prioritized gene to CRS associations. Among patients with breast cancer, differential germline associations with CRS were found by race, underscoring the need for larger, diverse datasets in molecular studies of breast cancer. These findings also suggest possible germline trans-regulation of PAM50 tumor expression, with potential implications for CRS interpretation in clinical settings.Significance:This study identifies race-specific genetic associations with breast cancer risk of recurrence scores and suggests mediation of these associations by PAM50 subtype and expression, with implications for clinical interpretation of these scores.
Phase I Dose-Escalation Trial of MIW815 (ADU-S100), an Intratumoral STING Agonist, in Patients with Advanced/Metastatic Solid Tumors or Lymphomas
Authors: Meric-Bernstam Funda , Sweis Randy F. , Hodi F. Stephen , Messersmith Wells A. , Andtbacka Robert H.I. , Ingham Matthew , Lewis Nancy , Chen Xinhui , Pelletier Marc , Chen Xueying , Wu Jincheng , Dubensky Thomas W. , McWhirter Sarah M. , Müller Thomas , Nair Nitya , Luke Jason J. 
Published: October 2021

Abstract

Purpose:
This phase I study assessed the safety, pharmacokinetics (PKs), and efficacy of MIW815 (ADU-S100), a novel synthetic cyclic dinucleotide that activates the stimulator of IFN genes (STING) pathway, in patients with advanced/metastatic cancers.

Patients and Methods:
Patients (n = 47) received weekly i.t. injections of MIW815, 50 to 6,400 μg, on a 3-weeks-on/1-week-off schedule.

Results:
A maximum tolerated dose was not reached. Most common treatment-related adverse events were pyrexia (17%), chills, and injection-site pain (each 15%). MIW815 was rapidly absorbed from the injection site with dose-proportional PK, a rapid terminal plasma half-life (approximately 24 minutes), and high interindividual variability. One patient had a partial response (PR; Merkel cell carcinoma); two patients had unconfirmed PR (parotid cancer, myxofibrosarcoma). Lesion size was stable or decreased in 94% of evaluable, injected lesions. RNA expression and immune infiltration assessments in paired tumor biopsies did not reveal significant on-treatment changes. However, increases in inflammatory cytokines and peripheral blood T-cell clonal expansion suggested systemic immune activation.

Conclusions:
MIW815 was well tolerated in patients with advanced/metastatic cancers. Clinical activity of single-agent MIW815 was limited in this first-in-human study; however, evidence of systemic immune activation was seen.