bluuebunny/crossref_metadata_2025_split huggingface dataset:
Reproductive choices and intrafamilial communication in neurogenetic diseases with different self-estimated severities
Authors: Pierron Lucie , Tezenas du Montcel Sophie , Heinzmann Anna , Coarelli Giulia , Héron Delphine , Heide Solveig , Herson Ariane , Hennessy Juliette , Petit Elodie , Gargiulo Marcela , Durr Alexandra 
Published: October 2022

BackgroundLow uptake of presymptomatic testing and medically assisted reproduction in families impacted by neurogenetic diseases prompted us to investigate how reproductive options are considered and whether there is a relationship with perceived severity of the disease. We hypothesised that self-estimated severity would influence opinion on reproductive options and that prenatal/preimplantation diagnosis would be a motivation to inform relatives about their risk.MethodsWe invited people impacted by neurogenetic diseases to evaluate the severity of their familial disease using analogic visual scales and to answer questionnaires about reproductive choices and intrafamilial communication. We compared answers between diseases and with the perceived severity of each disease.ResultsWe analysed 562 questionnaires. Participants were impacted by Huntington disease (n=307), spinocerebellar ataxias (n=114), Steinert myotonic dystrophy (n=82) and amyotrophic lateral sclerosis/frontotemporal dementia (n=59). Self-estimated severity differed between pathologies (p<0.0001). Overall, participants considered prenatal diagnosis (78.0±34.4 out of 100) and preimplantation diagnosis (75.2±36.1 out of 100) justified more than termination of pregnancy (68.6±38.5 out of 100). They were less in favour of gamete donation (48.3±39.8 out of 100) or pregnancy abstention (43.3±40.3 out of 100). The greater the perceived severity of the disease, the more reproductive options were considered justified, except for gamete donation. Prenatal/preimplantation diagnosis was a motivation to inform relatives for only 55.3% of participants (p=0.01).ConclusionSelf-estimated severity minimally impacts opinions towards reproductive options. Medically assisted reproduction procedures are rarely sought and do not motivate familial communication.
Intracranial hemorrhage in large vessel occlusion patients receiving endovascular thrombectomy with or without intravenous alteplase: a secondary analysis of the DIRECT-MT trial
Authors: Hu Xiaowei , Zhou Yu , Ospel Johanna , Yao Feirong , Liu Yizhi , Wang Hui , Li Bo , Hui Pinjing , Yang Pengfei , Zhang Yongwei , Zhang Lei , Li Zifu , Xing Pengfei , Shi Huaizhang , Han Hongxing , Wang Shouchun , Fang Qi , Liu Jianmin 
Published: October 2022

BackgroundAlteplase before thrombectomy for patients with large vessel occlusion stroke raises concerns regarding an increased risk of intracranial hemorrhage (ICH), but the details of this relationship are not well understood.MethodsThis was a secondary analysis of the DIRECT-MT trial. ICH and its subtypes were independently reviewed and classified according to the Heidelberg Bleeding Classification. The effects of alteplase before thrombectomy on ICH and ICH subtypes occurrence were evaluated using logistic regression. Clinical and imaging characteristics that may modify these effects were exploratorily tested.ResultsAmong 591 patients, any ICH occurred in 254 (43.0%), including hemorrhagic infarction type 1 in 12 (2.1%), hemorrhagic infarction type 2 in 127 (21.7%), parenchymal hematoma type 1 in 34 (5.8%), parenchymal hematoma type 2 in 50 (8.6%), and other hemorrhage types (3a-3c) in 24 (4.1%). Similar ICH frequencies were observed with combined alteplase and thrombectomy versus thrombectomy only (134/292 (45.9%) vs 120/299 (40.1%); OR 1.27, 95% CI 0.91 to 1.75, P=0.16), but patients treated with alteplase had a higher parenchymal hematoma rate (51/287 (17.8%) vs 33/297 (11.1%); OR 1.75, 95% CI 1.08 to 2.85, P=0.024). In the adjusted model, difference in parenchymal hematoma occurrence between groups remained significant (adjusted OR 1.71, 95% CI 1.00 to 2.92, P=0.049). Patients with history of diabetes (Pinteraction=0.048), hypertension (Pinteraction=0.02), antiplatelet therapy (Pinteraction=0.02), anticoagulation therapy (Pinteraction=0.04), and statin administration (Pinteraction=0.02) harbored a higher ICH rate when they received combination therapy.ConclusionsOur data showed that in the DIRECT-MT trial, alteplase did not increase overall ICH for large vessel occlusion patients treated with thrombectomy, but it increased the parenchymal hematoma rate.
‘Why They Laugh At Us?’: the functions and ethics of humour in Singaporean theatrical depictions of stigmatised illness
Authors: Hyder Sophia 
Published: October 2022

While humour in the context of illness might be perceived to be insensitive or inappropriate, it is used frequently in the medical setting and discussions of illness. This paper strives to answer why humour is used despite these feelings it might elicit, and attempts to outline conditions that inform the ethics of humour in an illness context.This paper analyses two Singaporean theatrical depictions of chronic and stigmatised illnesses: Haresh Sharma’sOff Centre(1993), which is about schizophrenia and depression, and Paddy Chew’s monologueCompletely With/Out Character(1999), on HIV and AIDS. In these plays, humour functions to: first, dispense information on stigmatised illnesses through mediation; second, implicate audiences in stigma-making through defamiliarisation; and third, to exert discursive control for feelings of empowerment. Furthermore, analysing these plays within their contexts demonstrate that humour is crucial for providing a more nuanced understanding of the stigmatised illness experience, since humour can illuminate culturally held notions of sickness and health.While humour is necessary for patients who are routinely misunderstood and alienated, it must be used with discretion to prevent abuse. As this paper demonstrates, the ethics of humour is more nuanced than simply possessing certain identity markers that provide the illusion of exoneration or inclusion. It is also affected by multiple axes of privilege and discrimination. In my conclusion, I argue that the ethics of humour in the illness context is contingent on whether imbalanced power relations and systems of oppression were employed and/or reproduced under the guise of non-seriousness.
Impact of 12 weeks of basic military training on testosterone and cortisol responses
Authors: L Tait Jamie , M Bulmer S , M Drake J , R Drain J , C Main L 
Published: October 2022

IntroductionMilitary personnel train and operate in challenging multistressor environments, which can affect hormonal levels, and subsequently compromise performance and recovery. The aims of this project were to evaluate concentrations of cortisol and testosterone and subjective perceptions of stress and recovery across basic military training (BMT).Methods32 male recruits undergoing BMT were tracked over a 12-week course. Saliva samples were collected weekly, on waking, 30 min postwaking and bedtime. Perceptions of stress and recovery were collected weekly. Daily physical activity (steps) were measured via wrist-mounted accelerometers across BMT. Physical fitness was assessed via the multistage fitness test and push-ups in weeks 2 and 8.ResultsConcentrations of testosterone and cortisol, and the testosterone:cortisol ratio changed significantly across BMT, with variations in responses concurrent with programmatic demands. Perceptions of stress and recovery also fluctuated according to training elements. Recruits averaged 17 027 steps per day between weeks 2 and 12, with week-to-week variations. On average, recruits significantly increased predicted VO2max(3.6 (95% CI 1.0 to 6.1) mL/kg/min) and push-ups (5. 5 (95% CI 1.4 to 9.7) repetitions) between weeks 2 and 8.ConclusionsRecruit stress responses oscillated over BMT in line with programmatic demands indicating that BMT was, at a group level, well-tolerated with no signs of enduring physiological strain or overtraining. The sensitivity of cortisol, testosterone and the testosterone:cortisol ratio to the stressors of military training, suggest they may have a role in monitoring physiological strain in military personnel. Subjective measures may also have utility within a monitoring framework to help ensure adaptive, rather than maladaptive (eg, injury, attrition), outcomes in military recruits.
Medication burden in young adults with juvenile idiopathic arthritis: data from a multicentre observational study
Authors: Montag Laura J , Horneff Gerd , Hoff Paula , Klein Ariane , Kallinich Tilmann , Foeldvari Ivan , Seipelt Eva , Tatsis Stefanie , Peer Aries MD , Niewerth Martina , Klotsche Jens , Minden Kirsten 
Published: October 2022

ObjectiveTo assess the medication and disease burden of young adults with juvenile idiopathic arthritis (JIA).MethodsYoung adults with JIA prospectively followed in the Juvenile Arthritis Methotrexate/Biologics long-term Observation reported on their health status and medication use. All medications taken (disease-modifying antirheumatic drugs (DMARDs)/prescription/over-the-counter drugs, but excluding most local therapies) classified according to the Anatomical Therapeutic Chemical Classification System were included in this analysis. Medication use at last follow-up was evaluated by sex, JIA category and time from symptom onset to the first biological DMARD (bDMARD) start.ResultsA total of 1306 young adults (68% female) with JIA and a mean disease duration of 13.6±6 years were included in the study. Patients reported using on average 2.4±2.1 medicines and 1.5±1.7 non-DMARD medicines, respectively, at the last follow-up. Almost a quarter of the patients reported polypharmacy. The higher the number of medications used was, the higher the disease activity, pain and fatigue, and the lower the quality of life of patients. Medication usage differed significantly between sexes and JIA categories, being highest in patients with rheumatoid factor-positive polyarthritis and systemic JIA. The number of medications used was significantly associated with the time from symptom onset to bDMARD start. Patients taking opioids or antidepressants had a particularly high disease burden and had received bDMARDs an average of 2 years later than patients not taking these medications.ConclusionMedication use in adults with JIA varies depending on sex, JIA category, and the time between symptom onset and initiation of treatment with bDMARD.
Live Feedback for Training Through Real-Time Data Visualizations: A Study with League of Legends
Authors: Rijnders Frans , Wallner Günter , Bernhaupt Regina 
Published: October 2022

With competitive gaming on the rise, players have developed an increased interest in data-driven feedback of their in-game performance. In many cases, this feedback is presented visually post-play but live companions that provide real-time analytics are gaining more and more attention. However, the design of such systems poses different requirements which have been little explored from a scholarly point of view.
In this paper, we report on a study of two visualizations - a physical and digital one - providing live feedback to League of Legends players designed based on a community survey (N= 175) and expert input. We further discuss results of a qualitative evaluation with 13 players and an expert, touch upon potential benefits and drawbacks of physical and digital implementations, and present derived design considerations and challenges for such real-time data visualizations, revolving around issues of information density, contextualization, representation, and a diverse range of user needs.
Model checking for a multi-execution memory model
Authors: Moiseenko Evgenii , Kokologiannakis Michalis , Vafeiadis Viktor 
Published: October 2022

Multi-execution memory models, such as Promising and Weakestmo, are an advanced class of weak memory
consistency models that justify certain outcomes of a concurrent program by considering multiple candidate executions collectively. While this key characteristic allows them to support effective compilation to hardware models and a wide range of compiler optimizations, it makes reasoning about them substantially more difficult. In particular, we observe that Promising and Weakestmo inhibit effective model checking because they allow some suprisingly weak behaviors that cannot be generated by examining one execution at a time.
We therefore introduce Weakestmo2, a strengthening of Weakestmo by constraining its multi-execution
nature, while preserving the important properties of Weakestmo: DRF theorems, compilation to hardware models, and correctness of local program transformations. Our strengthening rules out a class of surprisingly weak program behaviors, which we attempt to characterize with the help of two novel properties: load buffering race freedom and certification locality. In addition, we develop WMC, a model checker for Weakestmo2 with performance close to that of the best tools for per-execution models.
BFF: foundational and automated verification of bitfield-manipulating programs
Authors: Zhu Fengmin , Sammler Michael , Lepigre Rodolphe , Dreyer Derek , Garg Deepak 
Published: October 2022

Low-level systems code often needs to interact with data, such as page table entries or network packet headers, in which multiple pieces of information are packaged together as bitfield components of a single machine integer and accessed via bitfield manipulations (e.g., shifts and masking). Most existing approaches to verifying such code employ SMT solvers, instantiated with theories for bit vector reasoning: these provide a powerful hammer, but also significantly increase the trusted computing base of the verification toolchain.
In this work, we propose an alternative approach to the verification of bitfield-manipulating systems code, which we call BFF. Building on the RefinedC framework, BFF is not only highly automated (as SMT-based approaches are) but also foundational---i.e., it produces a machine-checked proof of program correctness against a formal semantics for C programs, fully mechanized in Coq. Unlike SMT-based approaches, we do not try to solve the general problem of arbitrary bit vector reasoning, but rather observe that real systems code typically accesses bitfields using simple, well-understood programming patterns: the layout of a bit vector is known up front, and its bitfields are accessed in predictable ways through a handful of bitwise operations involving bit masks. Correspondingly, we center our approach around the concept of a structured bit vector---i.e., a bit vector with a known bitfield layout---which we use to drive simple and predictable automation. We validate the BFF approach by verifying a range of bitfield-manipulating C functions drawn from real systems code, including page table manipulation code from the Linux kernel and the pKVM hypervisor.
Puppeteer: A Random Forest Based Manager for Hardware Prefetchers Across the Memory Hierarchy
Authors: Eris Furkan , Louis Marcia , Eris Kubra , Abellán José , Joshi Ajay 
Published: October 2022

Over the years, processor throughput has steadily increased. However, the memory throughput has not increased at the same rate, which has led to the memory wall problem in turn increasing the gap between effective and theoretical peak processor performance. To cope with this, there has been an abundance of work in the area of data/instruction prefetcher designs. Broadly, prefetchers predict future data/instruction address accesses and proactively fetch data/instructions in the memory hierarchy with the goal of lowering data/instruction access latency. To this end, one or more prefetchers are deployed at each level of the memory hierarchy, but typically, each prefetcher gets designed in isolation without comprehensively accounting for other prefetchers in the system. As a result, individual prefetchers do not always complement each other, and that leads to lower average performance gains and/or many negative outliers. In this work, we propose Puppeteer, which is a hardware prefetcher manager that uses a suite of random forest regressors to determine at runtime which prefetcher should be ON at each level in the memory hierarchy, such that the prefetchers complement each other and we reduce the data/instruction access latency. Compared to a design with no prefetchers, using Puppeteer we improve IPC by 46.0% in 1 one-core, 25.8% in four-core, and 11.9% in eight-core processors on average across traces generated from SPEC2017, SPEC2006, and Cloud suites with ~11-KB overhead. Moreover, we also reduce the number of negative outliers by more than 89%, and the performance loss of the worst-case negative outlier from 25% to only 5% compared to the state of the art.
Too Much Fuel on the Fire? Linking Obesity, Metabolism, and Melanoma Outcomes
Authors: Smalley Keiran S.M. 
Published: October 2022

SummaryPatients with metastatic melanoma who are overweight or obese have improved outcomes when treated with immunotherapies or targeted therapies. A recent study provides the first evidence that the host metabolic state influences the tumor metabolic phenotype, with implications for tumor progression and therapeutic response.See related article by Hahn et al., p. 154
A Novel Engineered AAV-Based Neoantigen Vaccine in Combination with Radiotherapy Eradicates Tumors
Authors: Huang Kevin Chih-Yang , Lai Chia-Ying , Hung Wei-Ze , Chang Hsin-Yu , Lin Pei-Chun , Chiang Shu-Fen , Ke Tao-Wei , Liang Ji-An , Shiau An-Cheng , Yang Pei-Chen , Chen William Tzu-Liang , Chao K.S. Clifford 
Published: October 2022

Abstract

The potency of tumor-specific antigen (TSA) vaccines, such as neoantigen (neoAg)-based cancer vaccines, can be compromised by host immune checkpoint inhibitory mechanisms, such as programmed cell death protein 1 (PD-1)/programmed death ligand 1 (PD-L1), that attenuate neoAg presentation on dendritic cells (DC) and hinder T cell–mediated cytotoxicity. To overcome PD-1/PD-L1 inhibition in DCs, we developed a novel adeno-associated virus (meAAV) neoAg vaccine, modified with TLR9 inhibitory fragments, PD-1 trap, and PD-L1 miRNA, which extend the persistence of meAAV and activate neoAg-specific T-cell responses in immune-competent colorectal and breast cancer murine models. Moreover, we found that in combination with radiotherapy, the meAAV-based neoAg cancer vaccine not only elicited higher antigen presentation ability, but also maintained neoAg-specific cytotoxic T lymphocyte (CTL) responses. These functional PD-1 traps and PD-L1 miRNAs overcome host PD-1/PD-L1 inhibitory mechanisms and boost the therapeutic efficacy of radiotherapy. More importantly, combined radiotherapy and meAAV neoAg cancer vaccines significantly enhanced neoAg-specific CTL responses, increased CTL infiltration in tumor microenvironment, and decreased tumor-associated immunosuppression. This process led to the complete elimination of colorectal cancer and delayed tumor growth of breast cancer in tumor-bearing mice. Taken together, our results demonstrated a novel strategy that combines neoAg cancer vaccine and radiotherapy to increase the therapeutic efficacy against colorectal and breast cancers.
Single High-Sensitivity Point-of-Care Whole-Blood Cardiac Troponin I Measurement to Rule Out Acute Myocardial Infarction at Low Risk
Authors: Apple Fred S. , Smith Stephen W. , Greenslade Jaimi H. , Sandoval Yader , Parsonage William , Ranasinghe Isuru , Gaikwad Niranjan , Schulz Karen , Stephensen Laura , Schmidt Christian W. , Okeson Brynn , Cullen Louise , Brownlee Emily , Fincher Gavin , Hall Emma , Hancock Rebecca , Gangathimmaiah Vinay , Hamilton-Craig Christian , Hobbins-King Andrew , Keijzers Gerben , Bayat Maryam Khorramshahi , McCormick Ellyse , Mahmoodi Ehsan , Perez Siegfried , Staib Andrew , Zournazi Anna , Than Martin 
Published: October 2022

Background:
High-sensitivity cardiac troponin (hs-cTn) laboratory assays are used to rule out myocardial infarction (MI) on presentation, but prolonged result turnaround times can delay patient management. Our primary aim was to identify patients at low risk of index MI using a rapid point-of-care (POC) whole-blood hs-cTnI assay at presentation with potential early patient discharge.

Methods:
Consecutive patients presenting to the emergency department from 2 prospective observational studies with suspected acute coronary syndrome were enrolled. A POC hs-cTnI assay (Atellica VTLi) threshold using whole blood at presentation, which resulted in a negative predictive value of ≥99.5% and sensitivity of >99% for index MI, was derived (SEIGE [Safe Emergency Department Discharge Rate]) and validated with plasma (SAMIE [Suspected Acute Myocardial Infarction in Emergency]). Event adjudications were established with hs-cTnI assay results from routine clinical care. The primary outcome was MI at 30 days.

Results:
A total of 1086 patients (8.1% with MI) were enrolled in a US derivation cohort (SEIGE) and 1486 (5.5% MI) in an Australian validation cohort (SAMIE). A derivation whole-blood POC hs-cTnI concentration of <4 ng/L provided a sensitivity of 98.9% (95% CI, 93.8%–100%) and negative predictive value of 99.5% (95% CI, 97.2%–100%) for ruling out MI. In the validation cohort, the sensitivity was 98.8% (95% CI, 93.3%–100%), and negative predictive value was 99.8% (95% CI, 99.1%–100%); 17.8% and 41.8%, respectively, were defined as low risk for discharge. The 30-day adverse cardiac events were 0.1% (n=1) for SEIGE and 0.8% (n=5) for SAMIE.

Conclusions:
A POC whole-blood hs-cTnI assay permits accessible, rapid, and safe exclusion of MI and may expedite discharge from the emergency department.

Registration:

URL:
https://www.clinicaltrials.gov
; Unique identifier: NCT04772157. URL:
https://www.australianclinicaltrials.gov.au/anzctr_feed/form
; Unique identifier: 12621000053820.