bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clinical outcomes associated with prostate cancer conspicuity on biparametric and multiparametric MRI: a protocol for a systematic review and meta-analysis of biochemical recurrence following radical prostatectomy
Authors: Morka Naomi , Simpson Benjamin S , Ball Rhys , Freeman Alex , Kirkham Alex , Kelly Daniel , Whitaker Hayley C , Emberton Mark , Norris Joseph M 
Published: May 2021

IntroductionThere is an increasing body of evidence to suggest that visibility of prostate cancer on magnetic resonance (MRI) may be related to likelihood of adverse pathological outcomes. Biochemical recurrence (BCR) after radical prostatectomy remains a significant clinical challenge and a means of predicting likelihood of this prior to surgery could inform treatment choice. It appears that MRI could be a potential candidate strategy for BCR prediction, and as such, there is a need to review extant literature on the prognostic capability of MRI. Here, we describe a protocol for a systematic review and meta-analysis of the utility of biparametric MRI (bpMRI) and multiparametric MRI (mpMRI) in predicting BCR following radical prostatectomy for prostate cancer treatment.Methods and analysisPubMed, MEDLINE, Embase and Cochrane databases will be searched and screening will be guided by the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. In order to meet the inclusion criteria, papers must be English-language articles involving patients who have had bpMRI or mpMRI for suspected prostate cancer and have undergone radical prostatectomy as definitive therapy. Patients must have had prostate-specific antigen monitoring before and after surgery. All relevant papers published from July 1977 to October 2020 will be eligible for inclusion. The Newcastle-Ottawa score will be used to determine the quality and bias of the studies. This protocol is written in-line with the PRISMA protocol 2015 checklist.Ethics and disseminationThere are no relevant ethical concerns. Dissemination of this protocol will be via peer-reviewed journals as well as national and international conferences.PROSPERO registration numberCRD42020206074.
LIVES for families psychological first aid training programme to address COVID-19 psychological distress: a mixed methods acceptability and feasibility protocol
Authors: Kimber Melissa , Harms Sheila , Soreni Noam , Inrig Maggie , Acai Anita , Lipman Ellen Louise , Sassi Roberto , Streiner David L , MacMillan Harriet L 
Published: May 2021

IntroductionBest practice approaches for addressing COVID-19-related psychological distress among young people (<25 years) and their families remain unclear. Psychological first aid (PFA) is promoted by public health authorities to provide psychological support in the context of extreme events; however, there is limited evidence for its effectiveness. As a prerequisite to conducting a randomised controlled trial to examine programme effectiveness, this project is evaluating the acceptability and feasibility of implementing and evaluating a PFA training programme (‘LIVES for Families’) for mental health (MH) practitioners to improve their ability to recognise and respond to COVID-19-related psychological distress among their clients.Methods and analysisWe are using a triangulation mixed methods research design; complementary strands of quantitative and qualitative data are being collected in parallel and will be merged at the interpretation phase of the project. The quantitative strand uses a repeated measures design; a consecutive sample of MH practitioners (n=80) providing MH support to young people or their families are being recruited to participate in the LIVES for Families PFA training programme and complete quantitative measures at baseline (pretraining), 2-week and 6-month follow-up time points. The qualitative strand uses fundamental description and semistructured interviews with a subset of practitioners (n=30), as well as managers of MH agencies (n=20). A mixed methods joint display and associated narrative will generate a comprehensive understanding regarding acceptability and feasibility.Ethics and disseminationThe Hamilton Integrated Research Ethics Board approved the study (project number: 11295). Results will be shared broadly with the policy and practice community through publications, presentations and public webinars. As a brief, evidence-informed intervention, the LIVES for Families PFA training programme is suitable in its mode of delivery across care settings. The outcomes of this study could have international implications for mitigating the MH impacts of viral pandemics.
Nationwide study on trends in unplanned hospital attendance and deaths during the 7 weeks after the onset of the COVID-19 pandemic in Denmark
Authors: Bogh Søren Bie , Fløjstrup Marianne , Nissen Søren Kabell , Hanson Stine , Bech Mickael , Johnsen Søren Paaske , Kristensen Mette Rahbek , Laugesen Line Emilie , Søndergaard Jens , Folkestad Lars , Christensen Erika Frischknecht , Henriksen Daniel Pilsgaard , Hsia Renee Y , Graham Colin A , Lindskou Tim Alex , Byg Keld-Erik , Søvsø Morten Breinholt , Laugesen Henrik , Hallas Peter , Mikkelsen Søren , Olsen Kim Rose , Thygesen Lau Caspar , Gamst-Jensen Hejdi , Brabrand Mikkel 
Published: May 2021

BackgroundThe impact of a pandemic on unplanned hospital attendance has not been extensively examined. The aim of this study is to report the nationwide consequences of the COVID-19 pandemic on unplanned hospital attendances in Denmark for 7 weeks after a ‘shelter at home’ order was issued.MethodsWe merged data from national registries (Civil Registration System and Patient Registry) to conduct a study of unplanned (excluding outpatient visits and elective surgery) hospital-based healthcare and mortality of all Danes. Using data for 7 weeks after the ‘shelter at home’ order, the incidence rate of unplanned hospital attendances per week in 2020 was compared with corresponding weeks in 2017–2019. The main outcome was hospital attendances per week as incidence rate ratios. Secondary outcomes were general population mortality and risk of death in-hospital, reported as weekly mortality rate ratios (MRRs).ResultsFrom 2 438 286 attendances in the study period, overall unplanned attendances decreased by up to 21%; attendances excluding COVID-19 were reduced by 31%; non-psychiatric by 31% and psychiatric by 30%. Out of the five most common diagnoses expected to remain stable, only schizophrenia and myocardial infarction remained stable, while chronic obstructive pulmonary disease exacerbation, hip fracture and urinary tract infection fell significantly. The nationwide general population MRR rose in six of the recorded weeks, while MRR excluding patients who were COVID-19 positive only increased in two.ConclusionThe COVID-19 pandemic and a governmental national ‘shelter at home’ order was associated with a marked reduction in unplanned hospital attendances with an increase in MRR for the general population in two of 7 weeks, despite exclusion of patients with COVID-19. The findings should be taken into consideration when planning for public information campaigns.
Joint Advisory Group on Gastrointestinal Endoscopy (JAG) framework for managing underperformance in gastrointestinal endoscopy
Authors: Ravindran Srivathsan , Thomas-Gibson Siwan , Siau Keith , Smith Geoff V , Coleman Mark , Rees Colin , Healey Chris 
Published: May 2021

Underperformance can be defined as performance which persistently falls below a desired minimum standard considered acceptable for patient care. Within gastrointestinal endoscopy, underperformance may be multifactorial, related to an individual’s knowledge, skills, attitudes, health or external factors. If left unchecked, underperformance has the potential to impact on care and ultimately patient safety. Managing underperformance should be a key attribute of high-quality endoscopy service, as recognised in the Joint Advisory Group on Gastrointestinal Endoscopy (JAG) accreditation process. However, it is recognised that not all services have robust mechanisms to do this.This article provides the JAG position on managing underperformance in endoscopy, defined through a practical framework. This follows a stepwise process of detecting underperformance, verification, identification of additional causative factors, providing support and reassessment. Detection and verification of issues may require use of multiple evidence sources, including performance data, feedback and appraisal reports. Where technical underperformance is identified, this should be risk stratified by potential risk to patient safety. Support should be tailored to each individual case based on the type of underperformance detected, any causative factors with an action plan developed. Support may include coaching, mentoring, training and upskilling. Wider support from the medical director’s office or external services may also be required. Monitoring and reassessment is a crucial part of the overall process.
Effectiveness of a multidisciplinary clinical pathway for women with systemic lupus erythematosus and/or antiphospholipid syndrome
Authors: Wind Merlijn , Hendriks Maike , van Brussel Bernadette T J , Eikenboom Jeroen , Allaart Cornelia F , Lamb Hildo J , Siebelink Hans-Marc J , Ninaber Maarten K , van Geloven Nan , van Lith Jan M M , Huizinga Tom W J , Rabelink Ton J , Sueters Marieke , Teng Y K Onno 
Published: May 2021

ObjectivesSLE and/or antiphospholipid syndrome (SLE/APS) are complex and rare systemic autoimmune diseases that predominantly affect women of childbearing age. Women with SLE/APS are at high risk of developing complications during pregnancy. Therefore, clinical practice guidelines recommend that patients with SLE/APS should receive multidisciplinary counselling before getting pregnant. We investigated the clinical effectiveness of implementing a multidisciplinary clinical pathway including prepregnancy counselling of patients with SLE/APS.MethodsA clinical pathway with specific evaluation and prepregnancy counselling for patients with SLE/APS was developed and implemented in a tertiary, academic hospital setting. Patients were prospectively managed within the clinical pathway from 2014 onwards and compared with a retrospective cohort of patients that was not managed in a clinical pathway. Primary outcome was a combined outcome of disease flares for SLE and thromboembolic events for APS. Secondary outcomes were maternal and fetal pregnancy complications.ResultsSeventy-eight patients with 112 pregnancies were included in this study. The primary combined outcome was significantly lower in the pathway cohort (adjusted OR (aOR) 0.20 (95% CI 0.06 to 0.75)) which was predominantly determined by a fivefold risk reduction of SLE flares (aOR 0.22 (95% CI 0.04 to 1.09)). Maternal and fetal pregnancy complications were not different between the cohorts (respectively, aOR 0.91 (95% CI 0.38 to 2.17) and aOR 1.26 (95% CI 0.55 to 2.88)).ConclusionsThe outcomes of this study suggest that patients with SLE/APS with a pregnancy wish benefit from a multidisciplinary clinical pathway including prepregnancy counselling.
Clopidogrel with aspirin in High-risk patients with Acute Non-disabling Cerebrovascular Events II (CHANCE-2): rationale and design of a multicentre randomised trial
Authors: Wang Yongjun , Johnston Claiborne , Bath Philip M , Meng Xia , Jing Jing , Xie Xuewei , Wang Anxin , Pan Yuesong , Xu Anding , Dong Qiang , Wang Yilong , Zhao Xingquan , Li Zixiao , Li Hao 
Published: May 2021

BackgroundIn patients with a minor ischaemic stroke or transient ischaemic attack (TIA), separate trials have shown that dual antiplatelet therapy with clopidogrel plus aspirin (clopidogrel–aspirin) or ticagrelor plus aspirin (ticagrelor–aspirin) are more effective than aspirin alone in stroke secondary prevention. However, these two sets of combination have not been directly compared. Since clopidogrel was less effective in stroke patients who wereCYP2C19loss-of-function (LOF) allele carriers, whether ticagrelor–aspirin is clinically superior to clopidogrel–aspirin in this subgroup of patients with stroke is unclear.AimTo describe the rationale and design considerations of the Clopidogrel in High-risk patients with Acute Non-disabling Cerebrovascular Events (CHANCE-2) trial.DesignCHANCE-2 is a randomised, double-blind, double-dummy, placebo-controlled, multicentre trial that compares two dual antiplatelet strategies for minor stroke or TIA patients who areCYP2C19 LOFallele carriers: ticagrelor (180 mg loading dose on day 1 followed by 90 mg twice daily on days 2–90) or clopidogrel (300 mg loading dose on day 1 followed by 75 mg daily on days 2–90), plus open-label aspirin with a dose of 75–300 mg on day 1 followed by 75 mg daily on day 2–21. All will be followed for 1 year.Study outcomesThe primary efficacy outcome is any stroke (ischaemic or haemorrhagic) within 3 months and the primary safety outcome is any severe or moderate bleeding event within 3 months.DiscussionThe CHANCE-2 trial will evaluate whether ticagrelor–aspirin is superior to clopidogrel–aspirin for minor stroke or TIA patients who areCYP2C19LOF allele carriers.Trial registration numberNCT04078737.
The effect of muscle blood flow restriction on hemodynamics, cerebral oxygenation and activation at rest
Authors: Cherouveim Evgenia D. , Miliotis Panagiotis G. , Dipla Konstantina , Koskolou Maria D. , Vrabas Ioannis S. , Geladas Nikolaos D. 
Published: May 2021

This study tested the hypothesis that muscle blood flow restriction reduces muscle and cerebral oxygenation at rest. In 26 healthy males, aged 33 ± 2 yrs, physiological variables were continuously recorded during a 10-min period in 2 experimental conditions: a) with muscle blood flow restriction through thigh cuffs application inflated at 120 mm Hg (With Cuffs, WC) and b) without restriction (No Cuffs, NC). Muscle and cerebral oxygenation were reduced by muscle blood flow restriction as suggested by the increase in both muscle and cerebral deoxygenated hemoglobin (Δ[HHb]; p < 0.01) and the decrease of muscle and cerebral oxygenation index (Δ[HbDiff]; p < 0.01). Hemodynamic responses were not affected by such muscle blood flow restriction, whereas baroreflex sensitivity was reduced (p = 0.009). The perception of leg discomfort was higher (p < 0.001) in the WC than in the NC condition. This study suggests that thigh cuffs application inflated at 120 mm Hg is an effective method to reduce muscle oxygenation at rest. These changes at the muscular level seem to be sensed by the central nervous system, evoking alterations in cerebral oxygenation and baroreflex sensitivity. Novelty: Thigh cuffs application inflated at 120 mm Hg effectively reduces muscle oxygenation at rest. Limiting muscle oxygenation appears to reduce cerebral oxygenation, and baroreflex sensitivity, at rest. Even in healthy subjects, limiting muscle oxygenation, at rest, affects neural integration.
Universal method for fabricating PDMS microfluidic device using SU8, 3D printing and soft lithography
Authors: Chande Charmi , Riaz Nida , Harbour Victoria , Noor Hathija , Torralba Monica , Cheng Yu-Hsuan , Li Zhenglong , Tong Anh , Voronov Roman , Basuray Sagnik 
Published: May 2021

Microfluidic devices are constructed from polydimethylsiloxane (PDMS) due to their biocompatibility, fabrication ease, well-established protocols, and simplicity. PDMS-based microfluidic devices are constructed by (i) applying liquid PDMS to a negative mold (usually a silicon or 3D-printed mold) and (ii) curing the PDMS with heat exposure over a set time period. Unreacted resin monomers in 3D-printed molds prevent PDMS from fully curing, resulting in improper channel formation in PDMS and reducing the PDMS device’s efficacy. An in-house protocol that uses SU-8 as a “non-stick” coating on 3D-printed molds facilitates the successful casting of PDMS. Contact angle, surface profile, optical profile, and force testing prove that PDMS cast from SU-8-treated molds resembles pristine PDMS, unlike PDMS cast from untreated molds. Further, this method is generalized to commercial 3D prints using different 3D printing resins. To demonstrate this technique’s viability in microfluidic devices, a microfluidic tree using PDMS from treated 3D prints shows vibrant colors and clear lines. This is absent from an untreated PDMS.
Tumor-Associated Stromal Cellular Density as a Predictor of Recurrence and Mortality in Breast Cancer: Results from Ethnically Diverse Study Populations
Authors: Abubakar Mustapha , Zhang Jing , Ahearn Thomas U. , Koka Hela , Guo Changyuan , Lawrence Scott M. , Mutreja Karun , Figueroa Jonine D. , Ying Jianming , Lissowska Jolanta , Lyu Ning , Garcia-Closas Montserrat , Yang Xiaohong Rose 
Published: May 2021

Abstract

Purpose:
Tumor-associated stroma is comprised of fibroblasts, tumor-infiltrating lymphocytes (TIL), macrophages, endothelial cells, and other cells that interactively influence tumor progression through inflammation and wound repair. Although gene-expression signatures reflecting wound repair predict breast cancer survival, it is unclear whether combined density of tumor-associated stromal cells, a morphologic proxy for inflammation and wound repair signatures on routine hematoxylin and eosin (H&E)-stained sections, is of prognostic relevance.

Methods:
By applying machine learning to digitized H&E-stained sections for 2,084 breast cancer patients from China (n = 596; 24–55 years), Poland (n = 810; 31–75 years), and the United States (n = 678; 55–78 years), we characterized tumor-associated stromal cellular density (SCD) as the percentage of tumor–stroma that is occupied by nucleated cells. Hazard ratios (HR) and 95% confidence intervals (CI) for associations between SCD and clinical outcomes [recurrence (China) and mortality (Poland and the United States)] were estimated using Cox proportional hazard regression, adjusted for clinical variables.

Results:
SCD was independently predictive of poor clinical outcomes in hormone receptor–positive (luminal) tumors from China [multivariable HR (95% CI)fourth(Q4) vs. first(Q1) quartile = 1.86 (1.06–3.26); Ptrend = 0.03], Poland [HR (95% CI)Q4 vs. Q1 = 1.80 (1.12–2.89); Ptrend = 0.01], and the United States [HR (95% CI)Q4 vs. Q1 = 2.42 (1.33–4.42); Ptrend = 0.002]. In general, SCD provided more prognostic information than most classic clinicopathologic factors, including grade, size, PR, HER2, IHC4, and TILs, predicting clinical outcomes irrespective of menopausal or lymph nodal status. SCD was not predictive of outcomes in hormone receptor–negative tumors.

Conclusions:
Our findings support the independent prognostic value of tumor-associated SCD among ethnically diverse luminal breast cancer patients.

Impact:
Assessment of tumor-associated SCD on standard H&E could help refine prognostic assessment and therapeutic decision making in luminal breast cancer.
TREM (Triggering Receptor Expressed on Myeloid Cells)-1 Inhibition Attenuates Neuroinflammation via PKC (Protein Kinase C) δ/CARD9 (Caspase Recruitment Domain Family Member 9) Signaling Pathway After Intracerebral Hemorrhage in Mice
Authors: Lu Qin , Liu Rui , Sherchan Prativa , Ren Reng , He Wei , Fang Yuanjian , Huang Yi , Shi Hui , Tang Lihui , Yang Shuxu , Zhang John H. , Tang Jiping 
Published: May 2021

Background and Purpose:
Intracerebral hemorrhage (ICH) is a devastating subtype of stroke with high mortality and disability. Inflammatory response promotes secondary brain injury after ICH. TREM (triggering receptor expressed on myeloid cells)-1 is a key regulator of inflammation. The aim of this study was to evaluate the role of TREM-1 in neuroinflammatory response after ICH in mice.

Methods:
CD1 mice (n=275) were used in this study. Mice were subjected to ICH by autologous blood injection. TREM-1 knockout CRISPR was administered intracerebroventricularly to evaluate the role of TREM-1 after ICH. A selective TREM-1 inhibitor, LP17, was administered intranasally 2 hours after ICH. To elucidate TREM-1 signaling pathway, CARD9 (caspase recruitment domain family member 9) activation CRISPR was administered with LP17 and TREM-1 activating anti-mouse TREM-1 monoclonal antibody (mAb) was administered with Rottlerin, a specific PKC (protein kinase C) δ inhibitor. Lastly, to evaluate the role of HMGB1 (high-mobility group box 1) in TREM-1 mediated microglia activation, glycyrrhizin, an inhibitor of HMBG1 was administered with TREM-1 activating mAb. Neurobehavioral test, brain water content, Western blot, immunofluorescence staining, and coimmunoprecipitation was performed.

Results:
TREM-1 knockout reduced ICH-induced neurobehavioral deficits and neuroinflammatory response. The temporal expression of HMGB1, TREM-1, PKC δ, and CARD9 increased after ICH. TREM-1 was expressed on microglia. Intranasal administration of LP17 significantly decreased brain edema and improved neurobehavioral outcomes at 24 and 72 hours after ICH. LP17 promoted M2 microglia polarization and reduced proinflammatory cytokines after ICH, which was reversed with CARD9 activation CRISPR. TREM-1 mAb increased neurobehavior deficits, proinflammatory cytokines, and reduced M2 microglia after ICH, which was reversed with Rottlerin. HMBG1 interaction with TREM-1 increased after ICH, and glycyrrhizin reduced neuroinflammation and promoted M2 microglia which was reversed with TREM-1 mAb.

Conclusions:
This study demonstrated that TREM-1 enhanced neuroinflammation by modulating microglia polarization after ICH, and this regulation was partly mediated via PKC δ/CARD9 signaling pathway and increased HMGB1 activation of TREM-1.
Neural OCR Post-Hoc Correction of Historical Corpora
Authors: Lyu Lijun , Koutraki Maria , Krickl Martin , Fetahu Besnik 
Published: May 2021

Abstract
Optical character recognition (OCR) is crucial for a deeper access to historical collections. OCR needs to account for orthographic variations, typefaces, or language evolution (i.e., new letters, word spellings), as the main source of character, word, or word segmentation transcription errors. For digital corpora of historical prints, the errors are further exacerbated due to low scan quality and lack of language standardization.
For the task of OCR post-hoc correction, we propose a neural approach based on a combination of recurrent (RNN) and deep convolutional network (ConvNet) to correct OCR transcription errors. At character level we flexibly capture errors, and decode the corrected output based on a novel attention mechanism. Accounting for the input and output similarity, we propose a new loss function that rewards the model’s correcting behavior.
Evaluation on a historical book corpus in German language shows that our models are robust in capturing diverse OCR transcription errors and reduce the word error rate of 32.3% by more than 89%.
Impact of SARS-CoV-2 on Aquaria: An Italian Perspective
Authors: Gili Claudia , Vasconi Mauro , Gagliardi Flavio 
Published: May 2021

Abstract
Aquatic animals have been maintained by humans in confined spaces since very ancient times. In the last century both, the need to implement seafood productions and the popularity of aquatic exhibits, have facilitated professional scientific development of live fish management techniques. In this context, aquatic animal welfare has therefore become an important standpoint to guarantee good and safe quality of seafood and sustainable aquaria and zoological collections. At the end of 2019, SARS-CoV-2 severely affected human health in China and shortly became pandemic, hence influencing globally most types of businesses. All animal industries fully dependent on human daily activities and resources, have been severely impacted by human distancing and isolation protocols. During this world crisis, extensive changes in aquarium management procedures had to be applied. Specific contingency plans were developed to protect humans and to guarantee animal care, in order to avoid the risk for aquaria fading away.