bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ocular manifestations of congenital insensitivity to pain: a long-term follow-up
Authors: Elsana Baker , Gradstein Libe , Imtirat Ahed , Yagev Ronit , Barrett Chiya , Ling Galina , Abu Tailakh Muhammad , Baidousi Amjad , Tsumi Erez 
Published: March 2021

AimTo describe ocular manifestations in children with congenital insensitivity to pain with and without anhidrosis (CIPA and CIP).MethodsWe reviewed records of eye examinations of 39 children diagnosed with CIPA or CIP. We collected clinical data, with particular attention to ocular surface findings. Corneal sensitivity was tested by presence of a blink reflex upon touching the cornea. Statistical analysis assessed differences in manifestations between the two conditions, and relationships among corneal sensitivity, presence of corneal opacities and visual acuity (VA).ResultsCIPA was diagnosed in 32 children and CIP in 7. The median follow-up periods were 50 months (CIPA group) and 94 months (CIP group). Corneal opacities were present in 23% of CIPA eyes and in 57% of CIP eyes. A blink reflex was positive in 52% of CIPA eyes and in 33% of CIP eyes. We recorded VA ≥20/25 in 36% of CIPA eyes, whereas all patients with CIP had VA ≤20/30. For the whole cohort, we found a negative correlation between a preserved blink reflex and the presence of corneal opacities, and a positive correlation between a preserved blink reflex and VA ≥20/25.ConclusionChildren with congenital insensitivity to pain are prone to develop corneal scarring. Patients with CIP tend to have more severe ocular surface disease than those with CIPA, probably due to more prevalent loss of corneal sensation. In both groups, a preserved blink reflex correlated with good vision. Affected children should have close follow-up to promptly treat ocular surface disease and prevent vision loss.
COVID-19 illness in relation to sleep and burnout
Authors: Kim Hyunju , Hegde Sheila , LaFiura Christine , Raghavan Madhunika , Luong Eric , Cheng Susan , Rebholz Casey M , Seidelmann Sara B 
Published: March 2021

BackgroundSleep habits and burnout have been shown to be associated with increase in infectious diseases, but it is unknown if these factors are associated with risk of COVID-19. We assessed whether sleep and self-reported burnout may be risk factors for COVID-19 among high-risk healthcare workers (HCWs).MethodsFrom 17 July to 25 September 2020, a web-based survey was administered to HCWs in six countries (France, Germany, Italy, Spain, UK, USA) with a high frequency of workplace exposure. Participants provided information on demographics, sleep (number of sleep hours at night, daytime napping hours, sleep problems), burnout from work and COVID-19 exposures. We used multivariable linear and logistic regression models to evaluate the associations between sleep, burnout and COVID-19.ResultsAmong 2884 exposed HCWs, there were 568 COVID-19 cases and 2316 controls. After adjusting for confounders, 1-hour longer sleep duration at night was associated with 12% lower odds of COVID-19 (p=0.003). Daytime napping hours was associated with 6% higher odds, but the association varied by countries, with a non-significant inverse association in Spain. Compared with having no sleep problems, having three sleep problems was associated with 88% greater odds of COVID-19. Reporting burnout ‘every day’ was associated with greater odds of COVID-19 (OR: 2.60, 95% CI 1.57 to 4.31, p trend across categories=0.001), longer duration (OR: 2.98, 95% CI 1.10 to 8.05, p trend=0.02) and severity (OR: 3.26, 95% CI 1.25 to 8.48, p trend=0.02) compared with reporting no burnout. These associations remained significant after adjusting for frequency of COVID-19 exposures.ConclusionsIn six countries, longer sleep duration was associated with lower odds of COVID-19, but the association with daytime nap may not be consistent across countries. Greater sleep problems and high level of burnout were robustly associated with greater odds of COVID-19. Sleep and burnout may be risk factors for COVID-19 in high-risk HCWs.
FOOTPRINTS study protocol: rationale and methodology of a 3-year longitudinal observational study to phenotype patients with COPD
Authors: Crapo James , Gupta Abhya , Lynch David A , Vogel-Claussen Jens , Watz Henrik , Turner Alice M , Mroz Robert M , Janssens Wim , Ludwig-Sengpiel Andrea , Beck Markus , Langellier Bérengère , Ittrich Carina , Risse Frank , Diefenbach Claudia 
Published: March 2021

IntroductionA better understanding is needed of the different phenotypes that exist for patients with chronic obstructive pulmonary disease (COPD), their relationship with the pathogenesis of COPD and how they may affect disease progression. Biomarkers, including those associated with emphysema, may assist in characterising patients and in predicting and monitoring the course of disease. The FOOTPRINTS study (study 352.2069) aims to identify biomarkers associated with emphysema, over a 3-year period.Methods and analysisThe FOOTPRINTS study is a prospective, longitudinal, multinational (12 countries), multicentre (51 sites) biomarker study, which has enrolled a total of 463 ex-smokers, including subjects without airflow limitation (as defined by the 2015 Global Initiative for Chronic Obstructive Lung Disease (GOLD) strategy report), patients with COPD across the GOLD stages 1–3 and patients with COPD and alpha1-antitrypsin deficiency. The study has an observational period lasting 156 weeks that includes seven site visits and additional phone interviews. Biomarkers in blood and sputum, imaging data (CT and magnetic resonance), clinical parameters, medical events of special interest and safety are being assessed at regular visits. Disease progression based on biomarker values and COPD phenotypes are being assessed using multivariate statistical prediction models.Ethics and disseminationThe study protocol was approved by the authorities and ethics committees/institutional review boards of the respective institutions where applicable, which included study sites in Belgium, Canada, Denmark, Finland, Germany, Japan, Korea, Poland, Spain, Sweden, UK and USA; written informed consent has been obtained from all study participants. Ethics committee approval was obtained for all participating sites prior to enrolment of the study participants. The study results will be reported in peer-reviewed publications.Trial registration numberNCT02719184.
Ultrasound and surgical inspection of plantaris tendon involvement in chronic painful insertional Achilles tendinopathy: a case series
Authors: Alfredson Håkan , Masci Lorenzo , Spang Christoph 
Published: March 2021

ObjectivesChronic painful insertional Achilles tendinopathy is known to be difficult to manage. The diagnosis is not always easy because multiple different tissues can be involved. The plantaris tendon has recently been described to frequently be involved in chronic painful mid-portion Achilles tendinopathy. This study aimed to evaluate possible plantaris tendon involvement in patients with chronic painful insertional Achilles tendinopathy.MethodsNinety-nine consecutive patients (74 males, 25 females) with a mean age of 40 years (range 24–64) who were surgically treated for insertional Achilles tendinopathy, were included. Clinical examination, ultrasound (US)+Doppler examination, and surgical findings were used to evaluate plantaris tendon involvement.ResultsIn 48/99 patients, there were clinical symptoms of plantaris tendon involvement with pain and tenderness located medially at the Achilles tendon insertion. In all these cases, surgical findings showed a thick and wide plantaris tendon together with a richly vascularised fatty infiltration between the plantaris and Achilles tendon. US examination suspected plantaris involvement in 32/48 patients.ConclusionPlantaris tendon involvement can potentially be part of the pathology in chronic painful insertional Achilles tendinopathy and should be considered for diagnosis and treatment when there is distinct and focal medial pain and tenderness.Level of evidenceIV case series.
Advance directives and real-world end-of-life clinical practice: a case–control study
Authors: Dalmau-Bueno Albert , Saura-Lazaro Anna , Busquets Josep Ma , Bullich-Marín Ingrid , García-Altés Anna 
Published: March 2021

BackgroundAdvance directives (ADs) have been legally regulated to promote autonomy over health decisions among patients who later lose decision-making capacity.Aims and objectivesTo analyse the differences in clinical practice at end of life among people who had completed an AD versus those who had not.MethodsRetrospective case–control study (1:2), matched by age, sex, year, cause of death and region of residence. The data sources used were the ADs registry, central registry of insured persons, hospital discharge, pharmacy and billing databases, and the mortality registry. Conditional logistic regression models (crude and adjusted by socioeconomic level) were performed. The outcome variable was the frequency of medical procedures performed during the last year of life.Results1723 people with ADs who died in Catalonia during 2014–2015 were matched with 3446 dead controls (without ADs). Thoracentesis was the procedure with the greatest reduction among women with an AD (adjusted OR (ORadj) 0.54, 95% CI: 0.32 to 0.89) in conjunction with artificial nutrition (ORadj0.54, 95% CI: 0.31 to 0.95). Intubation was the procedure with the greatest reduction (ORadj0.56, 95% CI: 0.33 to 0.94) among men. Slight differences could be seen in the case of cancer deaths. There were no relevant differences when adjusting by socioeconomic level.ConclusionsADs are an effective tool to adjust the realisation of some procedures at end of life. These results can help better plan for the treatment of patients with ADs, as well as increase the awareness among clinical personnel, families and the general population.
Long-term outcomes after endoscopic treatment for Barrett’s neoplasia with radiofrequency ablation ± endoscopic resection: results from the national Dutch database in a 10-year period
Authors: van Munster Sanne , Nieuwenhuis Esther , Weusten Bas L A M , Alvarez Herrero Lorenza , Bogte Auke , Alkhalaf Alaa , Schenk B E , Schoon Erik J , Curvers Wouter , Koch Arjun D , van de Ven Steffi Elisabeth Maria , de Jonge Pieter Jan Floris , Tang Tjon J , Nagengast Wouter B , Peters Frans T M , Westerhof Jessie , Houben Martin H M G , Bergman Jacques JGHM , Pouw Roos E 
Published: March 2021

ObjectiveRadiofrequency ablation (RFA)±endoscopic resection (ER) is the preferred treatment for early neoplasia in Barrett’s oesophagus (BE). We aimed to report short-term and long-term outcomes for all 1384 patients treated in the Netherlands (NL) from 2008 to 2018, with uniform treatment and follow-up (FU) in a centralised setting.DesignEndoscopic therapy for early BE neoplasia in NL is centralised in nine expert centres with specifically trained endoscopists and pathologists that adhere to a joint protocol. Prospectively collected data are registered in a uniform database. Patients with low/high-grade dysplasia or low-risk cancer, were treated by ER of visible lesions followed by trimonthly RFA sessions of any residual BE until complete eradication of BE (CE-BE). Patients with ER alone were not included.ResultsAfter ER (62% of cases; 43% low-risk cancers) and median 1 circumferential and 2 focal RFA (p25-p75 0–1; 1–2) per patient, CE-BE was achieved in 94% (1270/1348). Adverse events occurred in 21% (268/1386), most commonly oesophageal stenosis (15%), all were managed endoscopically. A total of 1154 patients with CE-BE were analysed for long-term outcomes. During median 43 months (22–69) and 4 endoscopies (1–5), 38 patients developed dysplastic recurrence (3%, annual recurrence risk 1%), all were detected as endoscopically visible abnormalities. Random biopsies from a normal appearing cardia showed intestinal metaplasia (IM) in 14% and neoplasia in 0%. A finding of IM in the cardia was reproduced during further FU in only 33%, none progressed to neoplasia. Frequent FU visits in the first year of FU were not associated with recurrence risk.ConclusionIn a setting of centralised care, RFA±ER is effective for eradication of Barrett’s related neoplasia and has remarkably low rates of dysplastic recurrence. Our data support more lenient FU intervals, with emphasis on careful endoscopic inspection. Random biopsies from neosquamous epithelium and cardia are of questionable value.Netherlands trial register numberNL7039.
Nitrogen and phosphorus distribution in plant, soil, and leachate as affected by liquid hog manure and chemical fertilizers
Authors: Kokulan Vivekananthan , Wadu Mihiri C.W. Manimel , Akinremi Olalekan O. , Buckley K.E. 
Published: March 2021

A 2 yr field study was conducted on a coarse-textured soil in Manitoba, Canada, to investigate the effects of liquid hog manure (LHM) and chemical fertilizer application on barley (2005) and red spring wheat (2006) yields, crop nutrient uptake, and nitrogen (N) and phosphorus (P) movement to the environment. The treatments were LHM applied at two rates as 22 000 L·ha−1 (2500 gal·ac−1, abbreviated as M2500) and 43 000 L·ha−1 (5000 gal·ac−1, abbreviated as M5000) and two rates of chemical fertilizer to match total N and P in LHM treatments, F2500 and F5000, along with an unamended control. The M5000 and M2500 treatments showed similar grain yield and N and P uptake. However, M5000 and M2500 significantly increased grain yield by 67% and 78%, respectively, compared with the control in 2005. In 2006, wheat grain yields from M2500 and M5000 were 71% and 86% greater than the control. In 2005, leachate NO3-N concentrations and leaching loads were higher with chemical fertilizers than M2500. In 2005, the apparent recovery of applied N as leachate was 35% and 23% in F5000 and F2500 treatments, whereas it was 6% and 7% of applied N in M5000 and M2500 plots, respectively. However, the application of M5000 resulted in P accumulation near the surface and may increase the potential risk of P loss with runoff. Our results show that applying LHM at moderate rates (M2500) may ensure desirable crop yields comparable to higher rates of nutrient application with minimal potential losses relative to higher rates.
Hudson Strait Platform and Basins Tectono-Sedimentary Element, Northeast Canada
Authors: Pinet Nicolas , Lavoie Denis , Zhang Shunxin 
Published: March 2021

Abstract
The Hudson Strait Platform and basins Tectono-Sedimentary Element (HSPB TSE) is part of a major topographical feature that connects Hudson Bay and Foxe Basin with the Labrador Sea in the Canadian Arctic. The Paleozoic succession (Ordovician–Silurian) unconformably overlies the Precambrian basement and reaches a maximum preserved thickness of less than 600 m on the islands. High-resolution marine seismic data indicate that the offshore part of the Hudson Strait is underlain by several fault-controlled sub-basins with a half-graben geometry. The sedimentary succession in the sub-basins is thicker than the one preserved in nearby islands, and includes an upper sedimentary package for which the nature and age remain poorly constrained. Upper Ordovician source rocks have been mapped onshore. Known potential reservoir rocks consist of Ordovician clastics and Ordovician–Silurian reefs and dolostones.
Palaeomycology: a modern mycological view of fungal palynomorphs
Authors: Nuñez Otaño Noelia B. , Bianchinotti M. Virginia , Saparrat Mario C. N. 
Published: March 2021

Abstract
Fungal spores are increasingly used as reliable proxies in palaeoenvironmental reconstructions; however, little attention is paid to the ecological tolerances of the fungi themselves and the signal the fungi provide. This chapter provides a much-needed background in fungal biology and ecology of monophyletic Dikarya (Ascomycota and Basidiomycota), as well as taphonomic considerations which could be included in any use as palaeoecological indicators. It is intended to help those who are interested in using fungal spores as palaeoecological indicators to make more informed interpretations. A recapitulation of spore dispersal strategies and distances is presented for a better understanding of the transport mechanisms of fungal spores. Likewise, pigmentation is discussed, as it results in significant taphonomic bias in fossil fungal assemblages and, as some dark-coloured pigmentation is authigenic while some develops during taphonomy. A key element of this chapter is discussion of the environmental role of fungi, including modern v. palaeo-approaches to fungal ecology, fungal assemblages, and diversity patterns as diagnostic tools to infer palaeoenvironments.
Evaluation of the Use of Real-time 3D Graphics to Augment Therapeutic Music Sessions for Young People on the Autism Spectrum
Authors: Mcgowan John J. , Mcgregor Iain , Leplatre Gregory 
Published: March 2021

The present research evaluates the effectiveness of CymaSense, a real-time 3D visualisation application developed by the authors, as a means of improving the communicative behaviours of autistic participants through the addition of a visual modality within therapeutic music sessions. Autism spectrum condition (ASC) is a lifelong neurodevelopmental disorder that can affect people in a number of ways, commonly through difficulties in communication. A multi-sensory approach within music sessions encourages people with ASC to engage more with the act of creating music, and with the therapists, increasing their level of communication and social interaction beyond the sessions.This article presents a study evaluating the use of CymaSense within a series of therapeutic music sessions, and a follow-up series of semi-structured interviews. Eight adults with ASC participated in 12 sessions using a single case experimental design approach over a total period of 19 weeks. Using qualitative and quantitative data, the results show an increase in communicative behaviour, for both verbal and non-verbal participants, resulting from the use of CymaSense. Qualitative feedback from interviews provided insight into the factors that contribute to the successful use of the application, as well as aspects that could be improved.
Comprehensive Molecular Profiling of Desmoplastic Small Round Cell Tumor
Authors: Slotkin Emily K. , Bowman Anita S. , Levine Max F. , Dela Cruz Filemon , Coutinho Diego F. , Sanchez Glorymar I. , Rosales Nestor , Modak Shakeel , Tap William D. , Gounder Mrinal M. , Thornton Katherine A. , Bouvier Nancy , You Daoqi , Gundem Gunes , Gerstle Justin T. , Heaton Todd E. , LaQuaglia Michael P. , Wexler Leonard H. , Meyers Paul A. , Kung Andrew L. , Papaemmanuil Elli , Zehir Ahmet , Ladanyi Marc , Shukla Neerav 
Published: March 2021

AbstractDesmoplastic small round cell tumor (DSRCT) is characterized by the EWSR1–WT1 t(11;22) (p13:q12) translocation. Few additional putative drivers have been identified, and research has suffered from a lack of model systems. Next-generation sequencing (NGS) data from 68 matched tumor-normal samples, whole-genome sequencing data from 10 samples, transcriptomic and affymetrix array data, and a bank of DSRCT patient-derived xenograft (PDX) are presented. EWSR1–WT1 fusions were noted to be simple, balanced events. Recurrent mutations were uncommon, but were noted in TERT (3%), ARID1A (6%), HRAS (5%), and TP53 (3%), and recurrent loss of heterozygosity (LOH) at 11p, 11q, and 16q was identified in 18%, 22%, and 34% of samples, respectively. Comparison of tumor-normal matched versus unmatched analysis suggests overcalling of somatic mutations in prior publications of DSRCT NGS data. Alterations in fibroblast growth factor receptor 4 (FGFR4) were identified in 5 of 68 (7%) of tumor samples, whereas differential overexpression of FGFR4 was confirmed orthogonally using 2 platforms. PDX models harbored the pathognomic EWSR1–WT1 fusion and were highly representative of corresponding tumors. Our analyses confirm DSRCT as a genomically quiet cancer defined by the balanced translocation, t(11;22)(p13:q12), characterized by a paucity of secondary mutations but a significant number of copy number alterations. Against this genomically quiet background, recurrent activating alterations of FGFR4 stood out, and suggest that this receptor tyrosine kinase, also noted to be highly expressed in DSRCT, should be further investigated. Future studies of DSRCT biology and preclinical therapeutic strategies should benefit from the PDX models characterized in this study.Implications:These data describe the general quiescence of the desmoplastic small round cell tumor (DSRCT) genome, present the first available bank of DSRCT model systems, and nominate FGFR4 as a key receptor tyrosine kinase in DSRCT, based on high expression, recurrent amplification, and recurrent activating mutations.
AP-2α Regulates S-Phase and Is a Marker for Sensitivity to PI3K Inhibitor Buparlisib in Colon Cancer
Authors: Beck Anna C. , Cho Edward , White Jeffrey R. , Paemka Lily , Li Tiandao , Gu Vivian W. , Thompson Dakota T. , Koch Kelsey E. , Franke Christopher , Gosse Matthew , Wu Vincent T. , Landers Shannon R. , Pamatmat Anthony J. , Kulak Mikhail V. , Weigel Ronald J. 
Published: March 2021

Abstract

Activating protein 2 alpha (AP-2α; encoded by TFAP2A) functions as a tumor suppressor and influences response to therapy in several cancer types. We aimed to characterize regulation of the transcriptome by AP-2α in colon cancer. CRISPR-Cas9 and short hairpin RNA were used to eliminate TFAP2A expression in HCT116 and a panel of colon cancer cell lines. AP-2α target genes were identified with RNA sequencing and chromatin immunoprecipitation sequencing. Effects on cell cycle were characterized in cells synchronized with aphidicolin and analyzed by FACS and Premo FUCCI. Effects on invasion and tumorigenesis were determined by invasion assay, growth of xenografts, and phosphorylated histone H3 (PHH3). Knockout of TFAP2A induced significant alterations in the transcriptome including repression of TGM2, identified as a primary gene target of AP-2α. Loss of AP-2α delayed progression through S-phase into G2–M and decreased phosphorylation of AKT, effects that were mediated through regulation of TGM2. Buparlisib (BKM120) repressed in vitro invasiveness of HCT116 and a panel of colon cancer cell lines; however, loss of AP-2α induced resistance to buparlisib. Similarly, buparlisib repressed PHH3 and growth of tumor xenografts and increased overall survival of tumor-bearing mice, whereas, loss of AP-2α induced resistance to the effect of PI3K inhibition. Loss of AP-2α in colon cancer leads to prolonged S-phase through altered activation of AKT leading to resistance to the PI3K inhibitor, Buparlisib. The findings demonstrate an important role for AP-2α in regulating progression through the cell cycle and indicates that AP-2α is a marker for response to PI3K inhibitors.

Implications:
AP-2α regulated cell cycle through the PI3K cascade and activation of AKT mediated through TGM2. AP-2α induced sensitivity to Buparlisib/BKM120, indicating that AP-2α is a biomarker predictive of response to PI3K inhibitors.