bluuebunny/crossref_metadata_2025_split huggingface dataset:
Study design, rationale and methods of the Revitalising Informal Settlements and their Environments (RISE) study: a cluster randomised controlled trial to evaluate environmental and human health impacts of a water-sensitive intervention in informal settlements in Indonesia and Fiji
Authors: Leder Karin , Openshaw John J , Allotey Pascale , Ansariadi Ansariadi , Barker S Fiona , Burge Kerrie , Clasen Thomas F , Chown Steven L , Duffy Grant A , Faber Peter A , Fleming Genie , Forbes Andrew B , French Matthew , Greening Chris , Henry Rebekah , Higginson Ellen , Johnston David W , Lappan Rachael , Lin Audrie , Luby Stephen P , McCarthy David , O"Toole Joanne E , Ramirez-Lovering Diego , Reidpath Daniel D , Simpson Julie A , Sinharoy Sheela S , Sweeney Rohan , Taruc Ruzka R , Tela Autiko , Turagabeci Amelia R , Wardani Jane , Wong Tony , Brown Rebekah 
Published: January 2021

IntroductionIncreasing urban populations have led to the growth of informal settlements, with contaminated environments linked to poor human health through a range of interlinked pathways. Here, we describe the design and methods for the Revitalising Informal Settlements and their Environments (RISE) study, a transdisciplinary randomised trial evaluating impacts of an intervention to upgrade urban informal settlements in two Asia-Pacific countries.Methods and analysisRISE is a cluster randomised controlled trial among 12 settlements in Makassar, Indonesia, and 12 in Suva, Fiji. Six settlements in each country have been randomised to receive the intervention at the outset; the remainder will serve as controls and be offered intervention delivery after trial completion. The intervention involves a water-sensitive approach, delivering site-specific, modular, decentralised infrastructure primarily aimed at improving health by decreasing exposure to environmental faecal contamination. Consenting households within each informal settlement site have been enrolled, with longitudinal assessment to involve health and well-being surveys, and human and environmental sampling. Primary outcomes will be evaluated in children under 5 years of age and include prevalence and diversity of gastrointestinal pathogens, abundance and diversity of antimicrobial resistance (AMR) genes in gastrointestinal microorganisms and markers of gastrointestinal inflammation. Diverse secondary outcomes include changes in microbial contamination; abundance and diversity of pathogens and AMR genes in environmental samples; impacts on ecological biodiversity and microclimates; mosquito vector abundance; anthropometric assessments, nutrition markers and systemic inflammation in children; caregiver-reported and self-reported health symptoms and healthcare utilisation; and measures of individual and community psychological, emotional and economic well-being. The study aims to provide proof-of-concept evidence to inform policies on upgrading of informal settlements to improve environments and human health and well-being.EthicsStudy protocols have been approved by ethics boards at Monash University, Fiji National University and Hasanuddin University.Trial registration numberACTRN12618000633280; Pre-results.
Population-based study on the prevalence and clinical profile of adults with cerebral palsy in Northern Ireland
Authors: McConnell Karen , Livingstone Emma , Perra Oliver , Kerr C 
Published: January 2021

ObjectivesThis study aimed to report the prevalence and clinical characteristics of adults with cerebral palsy (CP) in a geographically defined region of the UK.Design and settingCross-sectional study using the Northern Ireland Cerebral Palsy Register (NICPR).ParticipantsAll validated cases known to the NICPR, born 1981–2001 and alive and resident in Northern Ireland at age 19 years were included.ResultsThe study included 1218 persons with CP aged 19–39 years, 46 of whom died in adulthood. The prevalence of CP was 2.38 per 1000. The majority of cases had spastic CP (n=1132/1218, 93%) and could walk (n=949/1218, 78%). Those that died in adulthood typically had bilateral spastic CP (n=39/46) and used a wheelchair (n=40/46).ConclusionThe prevalence of CP in adults is similar to other common neurological conditions such as multiple sclerosis and Parkinson’s disease. The needs of adults with CP vary widely with almost half having two or more associated impairments that may require multiprofessional and multiagency coordination. Results from this study can be used to inform transformation of health and care services for adults with CP.
Reduced foveal cone density in early idiopathic macular telangiectasia
Authors: Song Hongxin , Rossi Ethan A , Williams David R 
Published: January 2021

ObjectiveIdiopathic macular telangiectasia (MacTel) is considered primarily a vascular disease affecting juxtafoveal retinal capillaries. However, recent evidence suggests that neuronal changes may occur early in disease development. We used high-resolution adaptive optics retinal imaging to elucidate the foveal cone photoreceptor changes at a cellular level in patients with MacTel.Methods and analysisWe used adaptive optics scanning light ophthalmoscopy (AOSLO) to evaluate the foveal cone photoreceptors in the less-affected eye of patients with asymmetric MacTel. AOSLO images of cone photoreceptors were obtained in a 4°×4° area centred on the foveola. Individual cone positions were identified within a 2°×2° area centred on the fovea, using semiautomatic cone marking software with manual correction, permitting calculation of a map of cone density.ResultsIn all participants, one eye was affected with MacTel, the fellow eye was clinically normal or near normal, with visual acuity of 20/25 or better and subtle angiographic leakage. The foveal cone mosaics were continuous with tight packing and cones exhibited normal reflectivity. However, cone density was significantly lower for all participants (mean=80 733 cones/mm2) within 0.5° than the cone density previously reported for normal eyes.ConclusionsFoveal cone density is lower than normal in the clinically less-affected eyes of patients with asymmetric MacTel. This suggests that cone photoreceptor loss may precede classic obvious vascular changes in idiopathic MacTel.
Therapeutic thoracentesis symptoms and activity: a qualitative study
Authors: Twose Chloe , Ferris Rebecca , Wilson Andrew , Rahman Najib , Farquhar Morag , Mishra Eleanor 
Published: January 2021

IntroductionMalignant pleural effusions (MPEs) commonly occur in patients with advanced cancer. Drainage of fluid is used to relieve symptoms and improve quality of life.ObjectiveTo improve our understanding of how therapeutic aspiration affects symptoms and activities in patients with MPE.MethodsPatients presenting to the Pleural Clinic at Norfolk and Norwich University Hospital with a confirmed or suspected MPE participated in up to three semistructured interviews during their diagnostic/therapeutic pathway. Interviews were analysed using framework analysis by two researchers independently.ResultsSixteen patients participated. Symptoms reported before drainage included breathlessness, cough, chest pain, fatigue and anorexia. Symptoms affected their activities, including walking, bending over and socialisation. Patients described anxiety about the underlying diagnosis and fear of over-reliance on others. Expectations of drainage outcome varied, with some hoping for a cure and others hoping for any improvement. After drainage, breathlessness, chest pain and cough improved in some patients. They reported feeling and sleeping better, but fatigue and poor appetite remained. Participants were more active after aspiration, but the duration of improvement was a few days only. Despite this, patients still felt the procedure worthwhile.ConclusionOverall health and respiratory symptoms improved following drainage, but constitutional symptoms did not improve. This may be because constitutional symptoms are caused by the underlying cancer. This study suggests that clinicians should consider a range of symptoms, rather than just breathlessness, in planning outcomes for clinical trials. These results are important to inform patients about the potential benefits and duration of symptom improvement after therapeutic aspiration.
Early palliative intervention: effects on patient care satisfaction in advanced cancer
Authors: Mah Kenneth , Swami Nadia , O'Connor Brenda , Hannon Breffni , Rodin Gary , Zimmermann Camilla 
Published: January 2021

ObjectiveIn a cluster-randomised controlled trial of early palliative care (EPC) in advanced cancer, EPC was robustly associated with increased patient satisfaction with care. The present study evaluated mediational mechanisms underlying this EPC effect, including improved physical and psychological symptoms and quality of life, as well as relationships with healthcare providers and preparation for end of life.MethodParticipants with advanced cancer (n=461) completed measures at baseline and then monthly to 4 months. Mediational analyses, using a robust bootstrapping approach, focused on 3-month and 4-month follow-up data.ResultsAt 3 months, EPC decreased psychological symptoms, which resulted in greater satisfaction either directly (βindirect effect=0.05) or through greater quality of life (βindirect effect=0.02). At 4 months, EPC increased satisfaction through improved quality of life (βindirect effect=0.08). Physical symptom management showed no significant mediational effects at either time point. Better relationships with healthcare providers consistently mediated the EPC effect on patient satisfaction at 3 and 4 months, directly (βindirect effect=0.13–0.16) and through reduced psychological symptoms and/or improved quality of life (βindirect effect=0.00–0.02). At 4 months, improved preparation for end-of-life mediated EPC effects on satisfaction by enhancing quality of life (βindirect effect=0.01) or by reducing psychological symptoms and thereby increasing quality of life (βindirect effect=0.02).ConclusionEPC increases satisfaction with care in advanced cancer by attending effectively to patients’ emotional distress and quality of life, enhancing collaborative relationships with healthcare providers, and addressing concerns about preparation for end-of-life.Trial registration numberNCT01248624
Experiences, challenges and lessons learnt in medical staff redeployment during response to COVID-19
Authors: Sykes Anny , Pandit Meghana 
Published: January 2021

BackgroundThe response to the COVID-19 pandemic required redeployment of large numbers of staff to avoid acute services being overwhelmed. This unprecedented, previously unplanned redeployment occurred in a rapidly changing environment. This paper describes the process of redeployment at a teaching hospital and assessment of this by the redeployed doctors and redeployment team.ObjectiveIdentify key lessons from the redeployment process to inform resilience and future planning for further COVID-19 peaks.MethodsRedeployment team experiences and challenges were documented in real time and formal structured feedback obtained. All redeployed doctors were asked for quantitative and qualitative feedback regarding their experiences in two distinct acute areas with different approaches to staffing.Results63 redeployed staff and five members of the redeployment team completed feedback questionnaires. Most redeployed doctors (76%) were satisfied and had adequate support and training. Redeployment was associated with self-reported stress and anxiety in 95% with 59% describing this as moderate or greater. This was reduced by adequate communication, supervision and a sense of belonging to a firm with access to simple information making a significant difference. Awareness of and satisfaction with well-being support services was also high (71%).The redeployment team identified having a well-mixed team who met daily, an online portal and engagement with leads as the key factors for being successful.ConclusionRedeployment in response to COVID-19 was associated with reported stress and anxiety in most redeployed doctors. Communication, local induction and feeling valued and being part of a team helped reduce this.
Incidence and outcomes of intracerebral haemorrhage with mechanical compression hydrocephalus
Authors: Owen Bryce , Akbik Omar , Torbey Michel , Davis Herbert , Carlson Andrew P 
Published: January 2021

IntroductionIntracerebral haemorrhage (ICH) within deep structures adjacent to the third ventricle is associated with worse outcomes when compared with lobar ICH due to the critical role of deep nuclei in normal neurological functioning. New evidence suggests another contributing factor to poor outcome is obstruction of cerebrospinal fluid outflow by clot burden causing mechanical compression of the third ventricle. The authors reviewed the incidence and outcomes of mechanical compression ICH in order to identify this high-risk group which may potentially benefit from minimally invasive evacuation.MethodsPatients with spontaneous, non-traumatic, supratentorial ICH were identified retrospectively over a 30-month period. CT imaging was reviewed to assess location of the ICH, volume of the ICH, presence of hydrocephalus requiring external ventricular drain (EVD) placement, and time to clearing of the third ventricle. Hydrocephalus was then categorised as due to ‘primarily intraventricular haemorrhage (IVH)’, ‘primarily mechanical compression’ or ‘mixed’. Functional outcomes at discharge were assessed using the modified Rankin Score (mRS).Results287 patients met inclusion criteria, of which 39 (13.5%) patients developed hydrocephalus that required EVD. EVD patients had significantly higher mRS at discharge (p≤0.001) when compared with the non-EVD group. Lobar location was associated with lower odds of poor outcome compared with thalamic location (OR 0.107–0.560). Mechanical compression hydrocephalus was associated with poor outcome when compared with the primary IVH hydrocephalus subgroup (p=0.037) as well as longer time to clearing of the third ventricle (p=0.006).ConclusionsMechanical obstruction requiring EVD occurs in approximately (21/287) 7.3% of all patients with spontaneous supratentorial ICH. It is unknown if the worse morbidity in these subjects is purely related to damage to deep structures surrounding the third ventricle or if secondary damage from hydrocephalus could be mitigated with targeted minimally invasive clot evacuation.
Heterogeneity and incidence of non-response for changes in cardiorespiratory fitness following time-efficient sprint interval exercise training
Authors: Metcalfe Richard S , Vollaard Niels BJ 
Published: January 2021

Interindividual variability for training-induced changes in maximal oxygen uptake (VO2max) is well described following continuous aerobic and high-intensity interval training. Whether similar variability is observed following time-efficient sprint interval training with minimal training volume (i.e., reduced-exertion high-intensity interval training; REHIT) is unknown. We conducted a pooled analysis of n=117 (68 men) training participants (mean±SD: age: 30±10 y; VO2max: 34.8±7.5 ml·kg-1·min-1), who completed a VO2max assessment before and 3 days after 6 weeks of REHIT comprising of two 10-20 second ‘all-out’ cycling sprints per session, and n=40 no-intervention control participants (age: 30±13 y; VO2max: 31.5±6.5 ml·kg-1·min-1) who completed repeated VO2max tests over a comparable timeframe. Individual responses estimated using 50% confidence intervals derived from the technical error were interpreted against a smallest worthwhile change (SWC) of 1.75 ml·kg-1·min-1. The standard deviation of individual responses was 2.39 ml·kg-1·min-1 demonstrating clinically meaningful heterogeneity in training-induced changes in VO2max following REHIT that exceed the technical, biological and random within-subjects variability of VO2max assessment. The likely (75% probability) non-response rate was 18% (21/117), and 49% (57/117) of individuals demonstrated increases in VO2max likely higher than the SWC. We conclude that the well-described increase in VO2max following REHIT at the group level is subject to substantial variability in magnitude at an individual level. This has important implications for exercise prescription and can be harnessed to elucidate mechanisms of adaptation. Novelty: • There is substantial heterogeneity in VO2max responses following time-efficient sprint interval training • Proportion of non-response was 18% and ∽50% of individuals show clinically meaningful increases in VO2max
Lattice study of QCD at finite chiral density: topology and confinement
Authors: Astrakhantsev Nikita , Braguta V. V. , Kotov A. Yu. , Kuznedelev D. D. , Nikolaev A. A. 
Published: January 2021

AbstractIn this paper we study the properties of QCD at nonzero chiral density $$\rho _5$$

ρ
5

, which is introduced through chiral chemical potential $$\mu _5$$

μ
5

. The study is performed within lattice simulation of QCD with dynamical rooted staggered fermions. We first check that $$\rho _5$$

ρ
5

is generated at nonzero $$\mu _5$$

μ
5

and in the chiral limit observe $$\rho _5 \sim \varLambda _{QCD}^2 \mu _5$$

ρ
5

∼

Λ

QCD

2

μ
5

. We also test the possible connection between confinement and topological fluctuations. To this end, we measured the topological susceptibility $$\chi _{\mathrm{top}}$$

χ
top

and string tension $$\sigma $$
σ
for various values of $$\mu _5$$

μ
5

. We observed that string tension grows with $$\mu _5$$

μ
5

. It seems that topological susceptibility also rises with $$\mu _5$$

μ
5

, but to state this more reliably the uncertainties should be reduced. We believe that our results indicate possible connection between topological fluctuations and the strength of confinement.
SSD-based Workload Characteristics and Their Performance Implications
Authors: Yadgar Gala , Gabel MOSHE , Jaffer Shehbaz , Schroeder Bianca 
Published: January 2021

Storage systems are designed and optimized relying on wisdom derived from analysis studies of file-system and block-level workloads. However, while SSDs are becoming a dominant building block in many storage systems, their design continues to build on knowledge derived from analysis targeted at hard disk optimization. Though still valuable, it does not cover important aspects relevant for SSD performance. In a sense, we are “searching under the streetlight,” possibly missing important opportunities for optimizing storage system design.
We present the first I/O workload analysis designed with SSDs in mind. We characterize traces from four repositories and examine their “temperature” ranges, sensitivity to page size, and “logical locality.” We then take the first step towards correlating these characteristics with three standard performance metrics: write amplification, read amplification, and flash read costs. Our results show that SSD-specific characteristics strongly affect performance, often in surprising ways.
HDAC5 Loss Impairs RB Repression of Pro-Oncogenic Genes and Confers CDK4/6 Inhibitor Resistance in Cancer
Authors: Zhou Yingke , Jin Xin , Ma Jian , Ding Donglin , Huang Zhenlin , Sheng Haoyue , Yan Yuqian , Pan Yunqian , Wei Ting , Wang Liguo , Wu Heshui , Huang Haojie 
Published: January 2021

Abstract

The tumor-suppressor protein RB acts as a transcription repressor via interaction of its pocket domain with an LXCXE motif in histone deacetylase (HDAC) proteins such as HDAC1. Here, we demonstrate that HDAC5 deficient for the LXCXE motif interacts with both RB-N (via an FXXXV motif) and RB-C segments, and such interactions are diminished by phosphorylation of RB serine-249/threonine-252 and threonine-821. HDAC5 was frequently downregulated or deleted in human cancers such as prostate cancer. Loss of HDAC5 increased histone H3 lysine 27 acetylation (H3K27-ac) and circumvented RB-mediated repression of cell-cycle–related pro-oncogenic genes. HDAC5 loss also conferred resistance to CDK4/6 inhibitors such as palbociclib in prostate and breast cancer cells in vitro and prostate tumors in vivo, but this effect was overcome by the BET-CBP/p300 dual inhibitor NEO2734. Our findings reveal an unknown role of HDAC5 in RB-mediated histone deacetylation and gene repression and define a new mechanism modulating CDK4/6 inhibitor therapeutic sensitivity in cancer cells.

Significance:
This study defines a previously uncharacterized role of HDAC5 in tumor suppression and provides a viable strategy to overcome CDK4/6 inhibitor resistance in HDAC5-deficent cancer.
Targeting Oxidative Phosphorylation to Increase the Efficacy of Radio- and Immune-Combination Therapy
Authors: Boreel Daan F. , Span Paul N. , Heskamp Sandra , Adema Gosse J. , Bussink Johan 
Published: January 2021

AbstractAs tumors grow, they upregulate glycolytic and oxidative metabolism to support their increased and altered energetic demands. These metabolic changes have major effects on the tumor microenvironment. One of the properties leading to this aberrant metabolism is hypoxia, which occurs when tumors outgrow their often-chaotic vasculature. This scarcity of oxygen is known to induce radioresistance but can also have a disrupting effect on the antitumor immune response. Hypoxia inhibits immune effector cell function, while immune cells with a more suppressing phenotype become more active. Therefore, hypoxia strongly affects the efficacy of both radiotherapy and immunotherapy, as well as this therapy combination. Inhibition of oxidative phosphorylation (OXPHOS) is gaining interest for its ability to combat tumor hypoxia, and there are strong indications that this results in a reactivation of the immune response. This strategy decreases oxygen consumption, leading to better oxygenation of hypoxic tumor areas and eventually an increase in immunogenic cell death induced by radio-immunotherapy combinations. Promising preclinical improvements in radio- and immunotherapy efficacy have been observed by the hypoxia-reducing effect of OXPHOS inhibitors and several compounds are currently in clinical trials for their anticancer properties. Here, we will review the pharmacologic attenuation of tumor hypoxia using OXPHOS inhibitors, with emphasis on their impact on the intrinsic antitumor immune response and how this affects the efficacy of (combined) radio- and immunotherapy.
Association of Level and Increase in D‐Dimer With All‐Cause Death and Poor Functional Outcome After Ischemic Stroke or Transient Ischemic Attack
Authors: Hou Huiqing , Xiang Xianglong , Pan Yuesong , Li Hao , Meng Xia , Wang Yongjun 
Published: January 2021

Background
D‐dimer is involved in poor outcomes of stroke as a coagulation biomarker. We aimed to investigate the associations of the level and increase in D‐dimer between baseline and 90 days with all‐cause death or poor functional outcome in patients after ischemic stroke or transient ischemic attack.

Methods and Results

We collected data from the CNSRIII (Third China National Stroke Registry) study. The present substudy included 10 518 patients within 7 days (baseline) of ischemic stroke or transient ischemic attack and 6268 patients at 90 days. Poor functional outcome at 1 year was assessed on the basis of the modified Rankin Scale (≥3). Multivariable Cox regression or logistic regression was used to assess the association of D‐dimer levels with all‐cause death or poor functional outcome. D‐dimer levels at 90 days were lower than those at baseline (1.4 µg/mL versus 1.7 µg/mL;
P
<0.001). Higher baseline D‐dimer level was associated with all‐cause death (adjusted hazard ratio [HR], 1.77; 95% CI, 1.25–2.52;
P
=0.001) and poor functional outcome (adjusted odds ratio [OR], 1.49; 95% CI, 1.23–1.80;
P
<0.001) during 1‐year follow‐up. Higher D‐dimer level at 90 days was also associated with poor outcomes independently. Furthermore, an increase in D‐dimer levels between baseline and 90 days was associated with all‐cause death (since 90 days to 1 year after index event) (adjusted HR, 1.99; 95% CI, 1.12–3.53;
P
=0.019) but not with poor functional outcome (adjusted OR, 1.08; 95% CI, 0.82–1.41).

Conclusions
Our study shows that high level and an increase in D‐dimer between baseline and 90 days are associated with poor outcomes in patients after ischemic stroke or transient ischemic attack.