bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dataset for Pathology Reporting of Colorectal Cancer
Authors: Loughrey Maurice B. , Webster Fleur , Arends Mark J. , Brown Ian , Burgart Lawrence J. , Cunningham Chris , Flejou Jean-Francois , Kakar Sanjay , Kirsch Richard , Kojima Motohiro , Lugli Alessandro , Rosty Christophe , Sheahan Kieran , West Nicholas P. , Wilson Richard H. , Nagtegaal Iris D. 
Published: July 2021

Objective:
The aim of this study to describe a new international dataset for pathology reporting of colorectal cancer surgical specimens, produced under the auspices of the International Collaboration on Cancer Reporting (ICCR).

Background:
Quality of pathology reporting and mutual understanding between colorectal surgeon, pathologist and oncologist are vital to patient management. Some pathology parameters are prone to variable interpretation, resulting in differing positions adopted by existing national datasets.

Methods:
The ICCR, a global alliance of major pathology institutions with links to international cancer organizations, has developed and ratified a rigorous and efficient process for the development of evidence-based, structured datasets for pathology reporting of common cancers. Here we describe the production of a dataset for colorectal cancer resection specimens by a multidisciplinary panel of internationally recognized experts.

Results:
The agreed dataset comprises eighteen core (essential) and seven non-core (recommended) elements identified from a review of current evidence. Areas of contention are addressed, some highly relevant to surgical practice, with the aim of standardizing multidisciplinary discussion. The summation of all core elements is considered to be the minimum reporting standard for individual cases. Commentary is provided, explaining each element's clinical relevance, definitions to be applied where appropriate for the agreed list of value options and the rationale for considering the element as core or non-core.

Conclusions:
This first internationally agreed dataset for colorectal cancer pathology reporting promotes standardization of pathology reporting and enhanced clinicopathological communication. Widespread adoption will facilitate international comparisons, multinational clinical trials and help to improve the management of colorectal cancer globally.
Beyond the RCT: When are Randomized Trials Unnecessary for New Therapeutic Devices, and What Should We Do Instead?
Authors: Páez Arsenio , Rovers Maroeska , Hutchison Katrina , Rogers Wendy , Vasey Baptiste , McCulloch Peter 
Published: July 2021

Objective:
The aim of this study was to develop an evidence-based framework for evaluation of therapeutic devices, based on ethical principles and clinical evidence considerations

Summary Background Data:
Nearly all medical products which do not work solely through chemical action are regulated as medical devices. Their huge range of purposes, mechanisms of action and risks pose challenges for regulation. High-profile implantable device failures have fuelled concerns about the level of clinical evidence needed for market approval. Calls for more rigorous evaluation lack clarity about what kind of evaluation is appropriate, and are commonly interpreted as meaning more randomized controlled trials (RCTs). These are valuable where devices are genuinely new and claim to offer measurable therapeutic benefits. Where this is not the case, RCTs may be inappropriate and wasteful.

Methods:
Starting with a set of ethical principles and basic precepts of clinical epidemiology, we developed a sequential decision-making algorithm for identifying when an RCT should be performed to evaluate new therapeutic devices, and when other methods, such as observational study designs and registry-based approaches, are acceptable.

Results:
The algorithm clearly defines a group of devices where an RCT is deemed necessary, and the associated framework indicates that an IDEAL 2b study should be the default clinical evaluation method where it is not.

Conclusions:
The algorithm and recommendations are based on the principles of the IDEAL-D framework for medical device evaluation and appear eminently practicable. Their use would create a safer system for monitoring innovation, and facilitate more rapid detection of potential hazards to patients and the public.
Is tactical combat casualty care in terrorist attacks suitable for civilian first responders?
Authors: Borgers Felix , Van Boxstael Sam , Sabbe Marc 
Published: July 2021

INTRODUCTION
Prehospital management of intentional mass casualty incidents is a unique challenge to Emergency Medical Services. Tactical Combat Casualty Care (TCCC) and the use of tourniquets for extremity hemorrhage have already proven to reduce mortality on the battlefield. This literature review aims to determine the place of these military concepts in a civilian high-threat prehospital setting.

METHODS
The PubMed database was searched for articles published between January 1, 2000, and December 1, 2019, containing descriptions, discussions, or experiences of the application of tourniquets or other TCCC-based interventions in the civilian prehospital setting. Data extraction focused on identifying important common themes in the articles.

RESULTS
Of the 286 identified articles, 30 were selected for inclusion. According to the Oxford Centre for Evidence-based Medicine Levels of Evidence, overall level of evidence was low. Most articles were observational, retrospective cohort studies without a nontourniquet control group. Outcome measures and variables were variably reported. Two articles specifically analyzed tourniquet use during high-threat situations, and three described their application by law enforcement personnel. Overall, tourniquets were found to be effective in stopping major limb bleeding. Reported mortality was low and related complications appeared to be infrequent. Only four articles mentioned the application of other TCCC-based maneuvers, such as airway and respiratory management.

CONCLUSION
This literature review shows that tourniquets appear to be safe tools associated with few complications and might be effective in controlling major bleeding in civilian limb trauma. For example, during mass casualty incidents, their use could be justified. Training and equipping ambulance and police services to deal with massive bleeding could likewise improve interoperability and victim survival in a civilian high-threat prehospital setting. More qualitative research is needed to further evaluate the effects of hemorrhage control training for first responders on patient outcomes. Literature describing the application of other TCCC-based principles is limited, which makes it difficult to draw conclusions regarding their use in a civilian setting.

LEVEL OF EVIDENCE
Systematic review, level III.
Paracentral Acute Middle Maculopathy in Pregnancy
Authors: Scott Rachel A. , Bhat Nita , Bindiganavile Shruthi H. , Li Helen K. , Lee Andrew G. 
Published: July 2021

Abstract:
A 31-year-old previously healthy, pregnant woman presented with acute, unilateral, painless paracentral vision loss in the left eye. The results of neuroimaging studies were normal. Hypercoagulable workup was negative, and fundus examination showed no retinal emboli and no retinal vascular abnormalities. The patient had well-controlled blood pressure and did not have eclampsia/preeclampsia. Although a presumptive referral diagnosis of “optic neuritis” was made, optical coherence tomography (OCT) of the macula showed a hyperreflective band involving the inner nuclear layer, consistent with paracentral acute middle maculopathy (PAMM). Furthermore, OCT angiography (OCT-A) showed flow attenuation of the outer retinal capillary plexus, further supporting a diagnosis of PAMM in pregnancy. Clinicians should be aware of the benefit of OCT-A as a complement to macular OCT in the evaluation of acute monocular vision loss mimicking retrobulbar optic neuropathy, particularly when signs and findings of other retinal vasculopathy are absent. PAMM should be considered in pregnant patients with acute visual changes.
Is photosynthetic enhancement sustained through three years of elevated CO2exposure in 175-year oldQuercus robur?
Authors: Gardner A , Ellsworth DS , Crous KY , Pritchard J , MacKenzie AR 
Published: July 2021

AbstractCurrent carbon cycle models attribute rising atmospheric CO2as the major driver of the increased terrestrial carbon sink, but with substantial uncertainties. The photosynthetic response of trees to elevated atmospheric CO2is a necessary step, but not the only one, for sustaining the terrestrial carbon uptake, but can vary diurnally, seasonally and with duration of CO2exposure. Hence we sought to quantify the photosynthetic response of the canopy-dominant species,Quercus robur, in a mature deciduous forest to elevated CO2(eCO2) (+150 μmol mol-1CO2) over the first three years of a long-term free air CO2enrichment facility at the Birmingham Institute of Forest Research in central England (BIFoR FACE). Over three thousand measurements of leaf gas exchange and related biochemical parameters were conducted in the upper canopy to assess the diurnal and seasonal responses of photosynthesis during the 2ndand 3rdyear of eCO2exposure. Measurements of photosynthetic capacity via biochemical parameters, derived from CO2response curves, (VcmaxandJmax) together with leaf nitrogen concentrations from the pre-treatment year to the 3rdyear of eCO2exposure, were examined. We hypothesized an initial enhancement in light-saturated net photosynthetic rates (Asat) with CO2enrichment of ≈37% based on theory but also expected photosynthetic capacity would fall over the duration of the study. Over the three-year period, Asatof upper-canopy leaves was 33 ± 8 % higher (mean and standard error) in trees grown in eCO2compared with ambient CO2(aCO2), and photosynthetic enhancement decreased with decreasing light. There were no significant effects of CO2treatment onVcmaxorJmax, nor leaf nitrogen. Our results suggest that matureQ. roburmay exhibit a sustained, positive response to eCO2without photosynthetic downregulation, suggesting that, with adequate nutrients, there will be sustained enhancement in C assimilated by these mature trees. Further research will be required to understand the location and role of the additionally assimilated carbon.
Early initiation of corticosteroids in patients hospitalized with COVID-19 not requiring intensive respiratory support: cohort study
Authors: Crothers Kristina , DeFaccio Rian , Tate Janet , Alba Patrick R. , Goetz Matthew , Jones Barbara , King Joseph T. , Marconi Vincent , Ohl Michael E. , Rentsch Christopher T. , Rodriguez-Barradas Maria C. , Shahrir Shahida , Justice Amy C. , Akgün Kathleen M. ,   Veterans Aging Cohort Study Clinical COVID-19 Working Group
Published: July 2021

ABSTRACTObjectivesTo determine whether early oral or parenteral corticosteroids compared to no corticosteroids are associated with decreased mortality in patients hospitalized with coronavirus disease 2019 (COVID-19) who are not on intensive respiratory support (IRS) within 48 hours of admission.DesignObservational cohort studySettingNationwide cohort of patients receiving care in the Department of Veterans Affairs, a large integrated US national healthcare systemParticipants9,058 patients admitted to a Veterans Affairs Medical Center between June 7, 2020-December 5, 2020 within 14-days after SARS-CoV-2 positive test; exclusion criteria include less than a 48 hour stay, receipt of prior systemic corticosteroids, and no indication of acute medical care for COVID-19.Main outcome measure90-day all-cause mortalityResultsOf 9,058 total patients (95% men, median age 71 years, 27% black), 6,825 (75%) were not on IRS within 48 hours. Among the 3,025 patients on no oxygen, 598 (20%) received corticosteroids and 283 (9%) died; of 3,800 patients on low-flow nasal cannula oxygen (NC), 2,808 (74%) received corticosteroids and 514 (13%) died. In stratified, inverse probability weighted Cox proportional hazards models comparing those who did and did not receive corticosteroids, patients on no oxygen experienced an 89% increased risk for 90-day mortality (hazard ratio [HR] 1.89, 95% confidence interval [CI] 1.33 to 2.68); there was weak evidence of increased mortality among patients on NC (HR 1.21, 95% CI 0.94 to 1.57). Results were robust in subgroup analyses including restricting corticosteroids to dexamethasone, and in sensitivity analyses employing different modeling approaches.ConclusionsIn patients hospitalized with COVID-19, we found no evidence of a mortality benefit associated with early initiation of corticosteroids among those on no oxygen or NC in the first 48 hours, though there was evidence of potential harm. These real-world findings support that clinicians should consider withholding corticosteroids in these populations and further clinical trials may be warranted.
Single Cell Transcriptomics Reveals Cell Type Specific Diversification in Human Heart Failure
Authors: Koenig Andrew L. , Shchukina Irina , Andhey Prabhakar S , Zaitsev Konstantin , Lai Lulu , Amrute Junedh , Bajpai Geetika , Bredemeyer Andrea , Smith Gabriella , Jones Cameran , Terrebonne Emily , Rentschler Stacey L. , Artyomov Maxim N. , Lavine Kory J. 
Published: July 2021

AbstractHeart failure represents a major cause of morbidity and mortality worldwide. Single cell transcriptomics have revolutionized our understanding of cell composition and associated gene expression across human tissues. Through integrated analysis of single cell and single nucleus RNA sequencing data generated from 45 individuals, we define the cell composition of the healthy and failing human heart. We identify cell specific transcriptional signatures of heart failure and reveal the emergence of disease associated cell states. Intriguingly, cardiomyocytes converge towards a common disease associated cell state, while fibroblasts and myeloid cells undergo dramatic diversification. Endothelial cells and pericytes display global transcriptional shifts without changes in cell complexity. Collectively, our findings provide a comprehensive analysis of the cellular and transcriptomic landscape of human heart failure, identify cell type specific transcriptional programs and states associated with disease, and establish a valuable resource for the investigation of human heart failure.
Neural Fragility of the Intracranial EEG Network Decreases after Surgical Resection of the Epileptogenic Zone
Authors: Li Adam , Myers Patrick , Warsi Nebras , Gunnarsdottir Kristin M. , Kim Sarah , Jirsa Viktor , Ochi Ayako , Otusbo Hiroshi , Ibrahim George M. , Sarma Sridevi V. 
Published: July 2021

AbstractOver 15 million patients with epilepsy worldwide do not respond to medical therapy and may benefit from surgical treatment. In focal epilepsy, surgical treatment requires complete removal or disconnection of the epileptogenic zone (EZ). However, despite detailed multimodal pre-operative assessment, surgical success rates vary and may be as low as 30% in the most challenging cases. Here we demonstrate that neural fragility, a dynamical networked-system biomarker of epileptogenicity, decreases following successful surgical resection. Moreover, neural fragility increases or remains constant when seizure-freedom is not achieved. We demonstrate this retrospectively in a virtual patient with epilepsy using the Virtual Brain neuroinformatics platform, and subsequently on six children with epilepsy with pre- and post-resection intra-operative recordings. Finally, we compare neural fragility as a putative biomarker of epileptogenicity against established spectral metrics, such as high frequency oscillations and find that neural fragility is a superior biomarker of epileptogenicity.
Androgen receptor pathway activity assay for sepsis diagnosis and prediction of favorable prognosis
Authors: Bouwman Wilbert , Verhaegh Wim , van de Stolpe Anja 
Published: July 2021

AbstractIntroductionSepsis is a life-threatening complication of a bacterial infection. It is hard to predict which patients with a bacterial infection will develop sepsis, and accurate and timely diagnosis, as well as assessment of prognosis, is difficult. Aside from antibiotics-based treatment of the causative infection and circulation-supportive measures, treatment options remain limited. Better understanding of the immuno-pathophysiology of sepsis may lead to improved diagnostic and therapeutic solutions.Functional activity of the innate (inflammatory) and adaptive immune response is controlled by a dedicated set of cellular signal transduction pathways in the various immune cell types. To develop an immune response-based diagnostic assay for sepsis and provide novel therapeutic targets, signal transduction pathway activities were analyzed in whole blood samples from patients with sepsis.MethodsA validated and previously published set of signal transduction pathway (STP) assays, determining immune cell function, was used to analyze public Affymetrix expression microarray data from clinical studies containing data from pediatric and adult patients with sepsis. STP assays enable quantitative measurement of STP activity on individual patient sample data, and were used to calculate activity of androgen receptor (AR), estrogen receptor (ER), JAK-STAT1/2, JAK-STAT3, Notch, Hedgehog, TGFβ, FOXO-PI3K, MAPK-AP1, and NFκB signal transduction pathways.ResultsActivity of AR and TGFβ pathways was increased in children and adults with sepsis. Using the mean plus two standard deviations of normal pathway activity (in healthy individuals) as threshold, diagnostic assay parameters were determined. For diagnosis of pediatric sepsis, the AR pathway assay showed high sensitivity (77%) and specificity (97%), with a PPV of 99% and NPV of 50%. For prediction of favorable prognosis (survival), PPV was 95%, NPV was 21%. The TGFβ pathway activity assay performed slightly less for diagnosing sepsis, with a sensitivity of 64% and specificity of 98% (PPV 99%, NPV 39%).ConclusionThe AR and TGFβ pathways have an immunosuppressive role, suggesting a causal relation between increased pathway activity and sepsis immunopathology. STP assays have been converted to qPCR assays for further evaluation of clinical utility for sepsis diagnosis and prediction of prognosis, as well as for prediction of risk at developing sepsis in patients with a bacterial infection. STPs may present novel therapeutic targets in sepsis.
Screening power of STIR muscle MRI in Critical illness myo-neuropathy and GBS in the ICU
Authors: Maramattom Boby Varkey 
Published: July 2021

AbstractIntroductionCritical illness myo-neuropathy [CIMN] or ICU acquired weakness [CIMN] is a common cause of weakness in ICU patients. It is diagnosed by clinical features, nerve conduction studies and muscle/nerve biopsies.MethodsThe MRI muscle STIR images of 7 patients with suspected CIMN and 7 GBS patients were reviewed.ResultsAll 7 patients with CIMN showed diffuse muscle edema, predominating in the lower limbs. Only one patient with GBS showed abnormal MRI changes (14%) and MRI was normal in 86%. The sensitivity of MRI to detect CIMN was 100%, whereas the specificity was 85.7%. Thus, the positive predictive value of MRI in this situation was 87.5% and the negative predictive value was 100%.ConclusionsMuscle STIR imaging may help to differentiate between CIMN and GBS and can modify the diagnostic algorithm of CIMN.
Image and structured data analysis for prognostication of health outcomes in patients presenting to the Emergency Department during the COVID-19 pandemic
Authors: Butler Liam , Karabayir Ibrahim , Tootooni Mohammad Samie , Afshar Majid , Goldberg Ari , Akbilgic Oguz 
Published: July 2021

AbstractBackgroundPatients admitted to the emergency department (ED) with COVID-19 symptoms are routinely required to have chest radiographs and computed tomography (CT) scans. COVID-19 infection has been directly related to development of acute respiratory distress syndrome (ARDS) and severe infections lead to admission to intensive care and can also lead to death. The use of clinical data in machine learning models available at time of admission to ED can be used to assess possible risk of ARDS, need for intensive care unit (ICU) admission as well as risk of mortality. In addition, chest radiographs can be inputted into a deep learning model to further assess these risks.PurposeThis research aimed to develop machine and deep learning models using both structured clinical data and image data from the electronic health record (EHR) to adverse outcomes following ED admission.Materials and MethodsLight Gradient Boosting Machines (LightGBM) was used as the main machine learning algorithm using all clinical data including 42 variables. Compact models were also developed using 15 the most important variables to increase applicability of the models in clinical settings. To predict risk of the aforementioned health outcome events, transfer learning from the CheXNet model was implemented on our data as well. This research utilized clinical data and chest radiographs of 3571 patients 18 years and older admitted to the emergency department between 9th March 2020 and 29th October 2020 at Loyola University Medical Center.Main FindingsOur research results show that we can detect COVID-19 infection (AUC = 0.790 (0.746-0.835)) and predict the risk of developing ARDS (AUC = 0.781 (0.690-0.872), ICU admission (AUC = 0.675 (0.620-0.713)), and mortality (AUC = 0.759 (0.678-0.840)) at moderate accuracy from both chest X-ray images and clinical data.Principal ConclusionsThe results can help in clinical decision making, especially when addressing ARDS and mortality, during the assessment of patients admitted to the ED with or without COVID-19 symptoms.
Anxiety and depression symptoms after COVID-19 infection: results from the COVID Symptom Study app
Authors: Klaser Kerstin , Thompson Ellen J. , Nguyen Long H. , Sudre Carole H. , Antonelli Michela , Murray Benjamin , Canas Liane S. , Molteni Erika , Graham Mark S. , Kerfoot Eric , Chen Liyuan , Deng Jie , May Anna , Hu Christina , Guest Andy , Selvachandran Somesh , Drew David A , Modat Marc , Chan Andrew T. , Wolf Jonathan , Spector Tim D. , Hammers Alexander , Duncan Emma L. , Ourselin Sebastien , Steves Claire J. 
Published: July 2021

SummaryBackgroundMental health issues have been reported after SARS-CoV-2 infection. However, comparison to prevalence in uninfected individuals and contribution from common risk factors (e.g., obesity, comorbidities) have not been examined. We identified how COVID-19 relates to mental health in the large community-based COVID Symptom Study.MethodsWe assessed anxiety and depression symptoms using two validated questionnaires in 413,148 individuals between February and April 2021; 26,998 had tested positive for SARS-CoV-2. We adjusted for physical and mental pre-pandemic comorbidities, BMI, age, and sex.FindingsOverall, 26.4% of participants met screening criteria for general anxiety and depression. Anxiety and depression were slightly more prevalent in previously SARS-CoV-2 positive (30.4%) vs. negative (26.1%) individuals. This association was small compared to the effect of an unhealthy BMI and the presence of other comorbidities, and not evident in younger participants (≤40 years). Findings were robust to multiple sensitivity analyses. Association between SARS-CoV-2 infection and anxiety and depression was stronger in individuals with recent (<30 days) vs. more distant (>120 days) infection, suggesting a short-term effect.InterpretationA small association was identified between SARS-CoV-2 infection and anxiety and depression symptoms. The proportion meeting criteria for self-reported anxiety and depression disorders is only slightly higher than pre-pandemic.FundingZoe Limited, National Institute for Health Research, Chronic Disease Research Foundation, National Institutes of Health, Medical Research Council UK