bluuebunny/crossref_metadata_2025_split huggingface dataset:
Efficacy of prothrombin complex concentrate (PCC) versus fresh frozen plasma (FFP) in reducing perioperative blood loss in cardiac surgery: study protocol for a non-inferiority, randomised controlled trial
Authors: Pei Lijian , Sun Chen , Lv Hong , Zhang Yuelun , Shi Jia 
Published: February 2022

ObjectiveTo explore whether prothrombin complex concentrate (PCC) is not inferior to fresh frozen plasma (FFP) with regard to reducing perioperative blood loss in patients undergoing cardiac surgery under cardiopulmonary bypass (CPB).SettingFu Wai Hospital, and Peking Union Medical College Hospital in China.ParticipantsPatients undergoing elective coronary artery bypass grafting, valve replacement or valvuloplasty under CPB, between 18 and 80 years old, will be included.DesignThis study is a non-inferiority, randomised controlled clinical trial. A total of 594 subjects will be randomly assigned to two groups (group PCC and group FFP) and given corresponding interventions when at least one of the following criteria is met: (1) international normalised ratio >1.7 measured 20 min after CPB, (2) prolonged prothrombin time or activated partial thromboplastin time (>1.5 times baseline) measured 20 min after CPB and (3) excessive bleeding observed. 4-factor PCC (15 IU/kg) and FFP (10 mL/kg) will be given to group PCC and group FFP, respectively. Preoperative management, anaesthetic and surgical techniques will be standardised for both groups.Primary and secondary outcome measuresThe primary outcome is the volume of blood loss during and within 24 hours after surgery. The secondary outcomes include (1) the total units of allogeneic red blood cells transfused during and within 7 days after surgery, (2) re-exploration due to postoperative bleeding within 7 days after surgery, (3) adverse events and serious adverse events within 30 days after surgery and (4) length of intensive care unit stay and hospital stay.Trial registration numberRegistered underNCT04244981at ClinicalTrials.gov on 28 January 2020,https://clinicaltrials.gov/ct2/show/NCT04244981?cond=NCT04244981&draw=2&rank=1.Ethics and disseminationThis study has been approved by the Institutional Review Board of Peking Union Medical College Hospital (ZS-2242).
Efficacy and safety of transcutaneous electrical nerve stimulation (TENS) for acute and chronic pain in adults: a systematic review and meta-analysis of 381 studies (the meta-TENS study)
Authors: Johnson Mark I. , Paley Carole A. , Jones Gareth , Mulvey Matthew R. , Wittkopf Priscilla G. 
Published: February 2022

ObjectiveTo investigate the efficacy and safety of transcutaneous electrical nerve stimulation (TENS) for relief of pain in adults.DesignSystematic review and meta-analysis.Data sourcesMedline, Cochrane Central, Embase (and others) from inception to July 2019 and updated on 17 May 2020.Eligibility criteria for study selectionRandomised controlled trials (RCTs) comparing strong non-painful TENS at or close to the site of pain versus placebo or other treatments in adults with pain, irrespective of diagnosis.Data extraction and synthesisReviewers independently screened, extracted data and assessed risk of bias (RoB, Cochrane tool) and certainty of evidence (Grading and Recommendations, Assessment, Development and Evaluation). Mean pain intensity and proportions of participants achieving reductions of pain intensity (≥30% or >50%) during or immediately after TENS. Random effect models were used to calculate standardised mean differences (SMD) and risk ratios. Subgroup analyses were related to trial methodology and characteristics of pain.ResultsThe review included 381 RCTs (24 532 participants). Pain intensity was lower during or immediately after TENS compared with placebo (91 RCTs, 92 samples, n=4841, SMD=−0·96 (95% CI −1·14 to –0·78), moderate-certainty evidence). Methodological (eg, RoB, sample size) and pain characteristics (eg, acute vs chronic, diagnosis) did not modify the effect. Pain intensity was lower during or immediately after TENS compared with pharmacological and non-pharmacological treatments used as part of standard of care (61 RCTs, 61 samples, n=3155, SMD = −0·72 (95% CI −0·95 to –0·50], low-certainty evidence). Levels of evidence were downgraded because of small-sized trials contributing to imprecision in magnitude estimates. Data were limited for other outcomes including adverse events which were poorly reported, generally mild and not different to comparators.ConclusionThere was moderate-certainty evidence that pain intensity is lower during or immediately after TENS compared with placebo and without serious adverse events.PROSPERO registration numberCRD42019125054.
What factors have influenced quality of life in people with dementia and their family carers during the COVID-19 pandemic: a qualitative study
Authors: Daley Stephanie , Akarsu Nazire , Armsby Elise , Farina Nicolas , Feeney Yvonne , Fine Bethany , Hughes Laura , Pooley Joanna , Tabet Naji , Towson Georgia , Banerjee Sube 
Published: February 2022

ObjectivesThe COVID-19 pandemic has led to significant disruption to health and social care services. For people with dementia and their family carers this is problematic, as a group who rely on timely and responsive services to live well with the condition. This study has sought to understand how COVID-19 has affected the quality of life of people diagnosed with dementia and their family carers.DesignOur mixed-methods study was nested in a larger cohort study of an education programme, Time for Dementia.SettingThe study took place in the South-East of England.ParticipantsExisting study participants, family carers were approached about the COVID-19 nested study. A purposeful sample of participants were invited to take part in in-depth qualitative interview. The sample included family carers in a range of different caring situations.MeasurementInterviews were undertaken remotely by telephone. Interviews sought to understand quality of life before the pandemic, impact of the restrictions on both the person with dementia and family carer, role of services and other agencies as well as supportive factors. Data were analysed using thematic analysis.Results16 family carers were interviewed. Seven themes were identified from our analysis: (1) decreased social interaction; (2) reduced support; (3) deteriorating cognitive and physical health for the person with dementia; (4) decreased carer well-being; (5) difficulties understanding COVID-19 restrictions; (6) limited impact for some and (7) trust and relationship with care home. There was little change between themes during the first and second wave of national lockdowns.ConclusionsOur study provides an understanding the short-term impact of COVID-19 on the quality of life of people with dementia and their family carers. Our findings suggest that recovery between the first and second wave of the restrictions did not automatically take place.
Using provider–parent strategies to improve influenza vaccination in children and adolescents with special risk medical conditions: a randomised controlled trial protocol
Authors: Tuckerman Jane , Harper Kelly , Sullivan Thomas R , Fereday Jennifer , Couper Jennifer , Smith Nicholas , Tai Andrew , Kelly Andrew , Couper Richard , Friswell Mark , Flood Louise , Danchin Margaret , Blyth Christopher C , Marshall Helen 
Published: February 2022

IntroductionInfluenza immunisation is a highly cost-effective public health intervention. Despite a comprehensive National Immunisation Program, influenza vaccination in children and adolescents with special risk medical conditions (SRMCs) is suboptimal. Flutext-4U is an innovative, multi-component strategy targeting paediatric hospitals, general practice and parents of children and adolescents with SRMC. The Flutext-4U study aims to assess the impact of Flutext-4U to increase influenza immunisation in children and adolescents with SRMC.Methods and analysisThis is a randomised controlled trial involving parents of children and adolescents (aged >6 months to <18 years) with SRMC receiving tertiary care at the Women’s and Children’s Hospital (WCH), Adelaide, South Australia, who are eligible for funded influenza immunisation with a hospital appointment between the start of the seasonal influenza vaccination season and 31 July 2021, their treating general practitioners (GPs), and WCH paediatric specialists.Parents (of children/adolescents with SRMC) are randomised (1:1 ratio) to standard care plus intervention (SMS reminder messages to parents; reminders (written correspondence) for their child’s GP from the hospital’s Paediatric Outpatients Department) or standard care (hospital vaccine availability, ease of access and reminders for WCH subspecialists) with randomisation stratified by age-group (<5, 5–14, >14 to <18 years).The primary outcome is influenza vaccination, as confirmed by the Australian Immunisation Register.The proportion vaccinated (primary outcome) will be compared between randomised groups using logistic regression, with adjustment made for age group at randomisation. The effect of treatment will be described using an OR with a 95% CI.Ethics and disseminationThe protocol and all study materials have been reviewed and approved by the Women’s and Children’s Health Network Human Research Ethics Committee (HREC/20/WCHN/5). Results will be disseminated via peer-reviewed publication and at scientific meetings, professional and public forums.Trial registration numberAustralian New Zealand Clinical Trials Registry (ACTRN12621000463875).
Who is engaging with lateral flow testing for COVID-19 in the UK? The COVID-19 Rapid Survey of Adherence to Interventions and Responses (CORSAIR) study
Authors: Smith Louise E , Potts Henry WW , Amlôt Richard , Fear Nicola T , Michie Susan , Rubin G James 
Published: February 2022

ObjectivesTo investigate uptake of lateral flow testing, reporting of test results and psychological, contextual and socio-demographic factors associated with testing.DesignA series of four fortnightly online cross-sectional surveys.SettingData collected from 19 April 2021 to 2 June 2021.ParticipantsPeople living in England and Scotland, aged 18 years or over, excluding those who reported their most recent test was a polymerase chain reaction (PCR) test (n=6646, n≈1600 per survey).Main outcome measuresHaving completed at least one lateral flow test (LFT) in the last 7 days.ResultsWe used binary logistic regressions to investigate factors associated with having taken at least one LFT. Increased uptake of testing was associated with being vaccinated (adjusted ORs (aORs)=1.52–2.45, 95% CI 1.25 to 3.07, analysed separately by vaccine dose), employed (aOR=1.94, 95% CI 1.63 to 2.32), having been out to work in the last week (aOR=2.30, 95% CI 1.94 to 2.73) and working in a sector that adopted LFT early (aOR=2.54, 95% CI 2.14 to 3.02) . Uptake was higher in people who reported cardinal COVID-19 symptoms in the last week (aOR=1.89, 95% CI 1.34 to 2.66). People who had heard more about LFTs (aOR=2.28, 95% CI 2.06 to 2.51) and knew they were eligible to receive regular LFTs (aOR=2.98, 95% CI 2.35 to 3.78) were also more likely to have tested. Factors associated with not taking a test included agreeing that you do not need to test for COVID-19 unless you have come into contact with a case (aOR=0.51, 95% CI 0.47 to 0.55).ConclusionsUptake of lateral flow testing is low. Encouraging testing through workplaces and places of study is likely to increase uptake, although care should be taken not to pressurise employees and students. Increasing knowledge that everyone is eligible for regular asymptomatic testing and addressing common misconceptions may drive uptake.
Impact of one and two human papillomavirus (HPV) vaccine doses on community-level HPV prevalence in South African adolescent girls: study protocol and rationale for a pragmatic before–after design
Authors: Machalek Dorothy , Rees Helen , Chikandiwa Admire , Munthali Richard , Travill Danielle , Mbulawa Zizipho , Petoumenos Kathy , Delany-Moretlwe Sinead , Kaldor John 
Published: February 2022

IntroductionVaccines against human papillomavirus (HPV) are the key to controlling cervical cancer in low/middle-income countries (LMICs) where incidence is highest, but there have been limited data from these settings on programme impact on HPV prevalence, and none in a population with endemic HIV infection. Furthermore, for many LMICs, the currently recommended two-dose schedule is difficult to deliver at scale, so there is mounting interest in a single-dose schedule.Methods and analysisThe Human Papillomavirus One and Two-Dose Population Effectiveness Study is a hybrid impact evaluation of the national South African HPV vaccination programme, which has targeted grade 4 girls aged at least 9 years in public schools with two doses of vaccine since 2014, and a single-dose vaccine ‘catch-up’ programme delivered in one district in 2019. Impacts of both schedules on the prevalence of type-specific HPV infection will be measured using repeat cross-sectional surveys in adolescent girls and young women aged 17–18 years recruited at primary healthcare clinics in the four provinces. A baseline survey in 2019 measured HPV prevalence in the cohort who were ineligible for vaccination because they were already above the target age or grade under either the national programme or the single-dose programme in the selected district. HPV prevalence surveys are repeated in 2021 in the selected district, and in 2023 in all four provinces. We will calculate prevalence ratios to compare the prevalence of HPV types 16 and 18 in the single-dose (2021) and two-dose (2023) cohorts, with the vaccine-ineligible (2019) cohort.Ethics and disseminationThe project was approved by the University of the Witwatersrand Human Research Ethics Committee (HREC #181005), and the University of New South Wales HREC (#181-005). Findings will be disseminated through peer-reviewed journals, scientific meetings, reports and community forums.
Thermoregulation by Bullsnakes (Pituophis catenifer sayi): do burrows make life easier on the prairies?
Authors: Johnson Noah B. , Poulin Ray G. , Somers Christopher M. 
Published: February 2022

Reptiles living in the grasslands of Western Canada cope with extremely variable environmental temperatures. We studied body temperatures (Tb) and operative environmental temperatures (Te) for Bullsnakes (Pituophis catenifer sayi (Schlegel, 1837)) to address uncertainties regarding challenges posed by the thermal environments of northern grasslands, and to evaluate conflicting hypotheses regarding thermoregulatory strategies. Despite potentially extreme surface temperatures (meanmin. = 9.3 °C, meanmax. = 31.4 °C), mammal burrows remained within voluntary limits (15–35 °C) for 93% of the active season and created thermal gradients (up to 27.2 °C) which may facilitate thermoregulation by creating high thermal heterogeneity. This evidence suggests that grasslands may actually be less challenging for thermoregulation than comparable forests. Fifty-eight percent (57.8%) of the variation in observed Tb (meanmin. = 20.1 °C, meanmax. = 29.1 °C) was explained by three simple variables: time of day, day of year, and bare ground Te. Bullsnakes thermoregulated by conforming to Te near their preferred range (21–27 °C), selecting locations that enabled heating up below this range and avoiding warmth above this range. Our results support broad hypotheses of reptilian thermoregulation that predict increased thermoregulation when (i) environmental temperatures deviate farther from preferred ranges and (ii) costs of thermoregulation are lower due to thermal heterogeneity.
Seismic geomorphology of submarine landslides in the Chalk Group of the Danish Central Graben: implications for reservoir potential
Authors: Smit Florian W. H. , Stemmerik Lars 
Published: February 2022

Abstract

This study documents a variety of deposits created by submarine landslides within the Upper Cretaceous to lowermost Paleocene Chalk Group in the Danish Central Graben and investigates the impact of remobilization on porosity. Improved visualization of the landslides in 3D seismic data compared with previous studies was facilitated by better seismic data quality for the Chalk Group, the availability of a large stack of stratigraphy-consistent horizons and the use of spectral decomposition data. The illustrated examples are chosen to reflect the spectrum of deformation styles seen in the chalk and all have a well penetrating the affected succession. They include a large collapse (375 km
2
) of an inversion ridge within the Kraka and Gorm formations, a field of large slide blocks (100–1000 m, 10–26 m) of likely lowermost Danian age embedded in the uppermost Ekofisk Formation, a debris flow system within the uppermost Tor Formation probably originating from the Ringkøbing–Fyn High and fine-grained bottom current sediment waves within the lowermost Danian Ekofisk Formation. In general, porosities are higher (10–25 porosity units) in the remobilized chalk compared with time-equivalent pelagic chalk in nearby reference wells. In earlier studies this has been linked to lack of bioturbation (resulting in limited grain repacking) in the remobilized chalks owing to high sedimentation rates, resulting in a relatively open fabric during initial burial. In contrast, surrounding and covering pelagic deposits could be much more effectively bioturbated, leading to tighter grain packing during burial. The insights of this study help in the seismic characterization of mud-grade carbonate oozes and have important applications in the reservoir modelling of mud-grade carbonate reservoirs (also in light of carbon capture and storage), and in palaeo-reconstructions of pelagic seafloors since submarine landslides provide kinematic indicators.
ARES: Persistently Secure Non-Volatile Memory with Processor-transparent and Hardware-friendly Integrity Verification and Metadata Recovery
Authors: Zou Yu , Zubair Kazi Abu , Alwadi Mazen , Shadab Rakin Muhammad , Gandham Sanjay , Awad Amro , Lin Mingjie 
Published: February 2022

Emerging byte-addressable Non-Volatile Memory (NVM) technology, although promising superior memory density and ultra-low energy consumption, poses unique challenges to achieving persistent data privacy and computing security, both of which are critically important to the embedded and IoT applications. Specifically, to successfully restore NVMs to their working states after unexpected system crashes or power failure, maintaining and recovering all the necessary security-related metadata can severely increase memory traffic, degrade runtime performance, exacerbate write endurance problem, and demand costly hardware changes to off-the-shelf processors.
In this article, we designed and implemented ARES, a new FPGA-assisted processor-transparent security mechanism that aims at efficiently and effectively achieving all three aspects of a security triad—confidentiality, integrity, and recoverability—in modern embedded computing. Given the growing prominence of CPU-FPGA heterogeneous computing architectures, ARES leverages FPGA’s hardware reconfigurability to offload performance-critical and security-related functions to the programmable hardware without microprocessors’ involvement. In particular, recognizing that the traditional Merkle tree caching scheme cannot fully exploit FPGA’s parallelism due to its sequential and recursive function calls, we (1) proposed a Merkle tree cache architecture that partitions a unified cache into multiple levels with parallel accesses and (2) further designed a novel Merkle tree scheme that flattened and reorganized the computation in the traditional Merkle tree verification and update processes to fully exploit the parallel cache ports and to fully pipeline time-consuming hashing operations. Beyond that, to accelerate the metadata recovery process, multiple parallel recovery units are instantiated to recover counter metadata and multiple Merkle sub-trees.
Our hardware prototype of the ARES system on a Xilinx U200 platform shows that ARES achieved up to 1.4× lower latency and 2.6× higher throughput against the baseline implementation, while metadata recovery time was shortened by 1.8 times. When integrated with an embedded processor, neither hardware changes nor software changes are required. We also developed a theoretical framework to analytically model and explain experimental results.
Resolving the Heterogeneous Tumor-Centric Cellular Neighborhood through Multiplexed, Spatial Paracrine Interactions in the Setting of Immune Checkpoint Blockade
Authors: Maus Rachel L.G. , Leontovich Alexey A. , Moore Raymond M. , Becher Laura , Nevala Wendy K. , Flotte Thomas J. , Guo Ruifeng , Schimke Jill M. , Dicke Betty A. , Yan Yiyi , Markovic Svetomir N. 
Published: February 2022

Direct interactions between tumor and immune cells mediate the antitumor effect of all modern cancer immunotherapeutic agents. Simultaneously, tumor cells have evolved mechanisms of evasion, including the downregulation of HLA-I, potentially disrupting the mechanism of action employed by many immune checkpoint inhibitors. And yet, the in situ interplay between these cells within the tumor immune microenvironment (TIME) remains elusive. Recent advances in histologic multiplex bioimaging platforms have enabled in-depth molecular characterization of single cells within spatially preserved and clinically archived tumor tissues. Herein, we applied multiplex immunofluorescence to excisional lymph node biopsies from 14 patients with metastatic melanoma who experienced clear objective responses to immunotherapy (7 complete response; 7 progressive disease) to determine distinguishing features of the TIME in the pretreatment setting. Distinct regions of the TIME were evaluated using 35 proteins probing tumor, immune, and vasculature components across 323 fields of view. Single-cell compositional analysis confirmed established prognostic immune cell types including increased prevalence of cytotoxic T cells within the tumor core fields of view of responders. Integrating single-cell quantification with the spatial arrangement of cellular neighborhoods surrounding tumor cells revealed novel, spatial immune signatures capable of stratifying TIME based on clinical response. Our analysis revealed dynamic cellular composition of the tumor-centric cellular neighborhood (TCCN) based on anatomic subregion, functional expression of HLA-I by the index tumor cell and ultimately clinical response to immunotherapy. Overall, this study provides an analytic framework to resolve the cellular complexity of the TIME, increasingly relevant to the outcomes of modern cancer immunotherapy.

Significance:
Findings from this work propose a novel approach to resolving clinical heterogeneity of the TIME by objectively quantifying the cellular interactions occurring in metastatic melanoma lymph node tissue utilizing multiplex immunofluorescence. This study provides an analytic and biologically derived unit of measure, the TCCN which is customizable for studying critical paracrine interactions within spatially preserved tissue of various cancers and across the spectrum of multiplex imaging modalities.