bluuebunny/crossref_metadata_2025_split huggingface dataset:
Improved quantitative detection of biotin‐labeled red blood cells by flow cytometry
Authors: Donnenberg Albert D. , Kanias Tamir , Triulzi Darrell J. , Dennis Catherine J. , Meyer E. Michael , Gladwin Mark 
Published: June 2019

BACKGROUNDBiotin‐labeled red blood cells (BioRBC) can be tracked after transfusion, providing a convenient and safe way to measure RBC survival in vivo. RBC survival is of interest for determining optimal blood storage conditions and for assessing the impact of genetic and biologic variants in blood donors on the survival of transfused RBCs. Here we present an improved, platform‐independent assay for quantifying biotin on BioRBC. This approach is also useful for detecting BioRBC in peripheral blood samples as rare events.STUDY DESIGN AND METHODSWe optimized the signal‐to‐noise ratio of the detecting reagent (phycoerythrin‐conjugated streptavidin [SA‐PE]) by determining the SA‐PE concentration yielding the greatest separation index between BioRBC and unlabeled RBCs. We calibrated the fluorescence intensity measurements to molecules of equivalent soluble fluorochrome (MESF), a quantitative metric of fluorochrome binding and therefore of biotin bound per RBC. We then characterized the limit of blank and limit of quantification (LoQ) for BioRBC labeled at different densities.RESULTSBiotin‐labeled RBCs at sulfo‐NHS‐biotin concentrations of 3 to 30 μg/mL (27‐271 nmol/mL RBCs) ranged from approximately 32,000 to 200,000 MESF/RBC. The LoQ ranged from one in 274,000 to one in 649,000, depending on biotin‐labeling density.CONCLUSIONIncreased sensitivity to detect BioRBC may facilitate tracking over longer periods and/or reduction of the BioRBC dose. Total RBC‐bound biotin dose has been shown to correlate with the likelihood of developing antibodies to BioRBC. Lowering the dose of labeled cells may help avoid this eventuality.
Healthy Public Policy Options to Promote Physical Activity for Chronic Disease Prevention: Understanding Canadian Policy Influencer and General Public Preferences
Authors: McGetrick Jennifer Ann , Kongats Krystyna , Raine Kim D. , Voyer Corinne , Nykiforuk Candace I.J. 
Published: June 2019

Background: Attitudes and beliefs of policy influencers and the general public toward physical activity policy may support or impede population-level action, requiring improved understanding of aggregate preferences toward policies that promote physical activity. Methods: In 2016, the Chronic Disease Prevention Survey was administered to a census sample of policy influencers (n = 302) and a stratified random sample of the public (n = 2400) in Alberta and Québec. Using net favorable percentages and the Nuffield Council on Bioethics’ intervention ladder framework to guide analysis, the authors examined support for evidence-based healthy public policies to increase physical activity levels. Results: Less intrusive policy options (ie, policies that are not always the most impactful) tended to have higher levels of support than policies that eliminated choice. However, there was support for certain types of policies affecting influential determinants of physical activity such as the built environment (ie, provided they enabled rather than restricted choice) and school settings (ie, focusing on children and youth). Overall, the general public indicated stronger levels of support for more physical activity policy options than policy influencers. Conclusions: The authors’ findings may be useful for health advocates in identifying support for evidence-based healthy public policies affecting more influential determinants of physical activity.
‘I have no love for such people, because they leave us to suffer’: a qualitative study of health workers’ responses and institutional adaptations to absenteeism in rural Uganda
Authors: Tweheyo Raymond , Reed Catherine , Campbell Stephen , Davies Linda , Daker-White Gavin 
Published: June 2019

BackgroundAchieving positive treatment outcomes and patient safety are critical goals of the healthcare system. However, this is greatly undermined by near universal health workforce absenteeism, especially in public health facilities of rural Uganda. We investigated the coping adaptations and related consequences of health workforce absenteeism in public and private not-for-profit (PNFP) health facilities of rural Uganda.MethodsAn empirical qualitative study involving case study methodology for sampling and principles of grounded theory for data collection and analysis. Focus groups and in-depth interviews were used to interview a total of 95 healthcare workers (11 supervisors and 84 frontline workers). The NVivo V.10 QSR software package was used for data management.ResultsThere was tolerance of absenteeism in both the public and PNFP sectors, more so for clinicians and managers. Coping strategies varied according to the type of health facility. A majority of the PNFP participants reported emotion-focused reactions. These included unplanned work overload, stress, resulting anger directed towards coworkers and patients, shortening of consultation times and retaliatory absence. On the other hand, various cadres of public health facility participants reported ineffective problem-solving adaptations. These included altering weekly schedules, differing patient appointments, impeding absence monitoring registers, offering unnecessary patient referrals and rampant unsupervised informal task shifting from clinicians to nurses.ConclusionHigh levels of absenteeism attributed to clinicians and health service managers result in work overload and stress for frontline health workers, and unsupervised informal task shifting of clinical workload to nurses, who are the less clinically skilled. In resource-limited settings, the underlying causes of absenteeism and low staff morale require attention, because when left unattended, the coping responses to absenteeism can be seen to compromise the well-being of the workforce, the quality of healthcare and patients’ access to care.
Mortality and cancer incidence among underground uranium miners in the Czech Republic 1977–1992
Authors: Kelly-Reif Kaitlin , Sandler Dale P , Shore David , Schubauer-Berigan Mary , Troester Melissa A , Nylander-French Leena , Richardson David B 
Published: June 2019

ObjectivesUranium miners in Příbram, Czech Republic were exposed to low and moderate levels of radon gas and other hazards. It is unknown whether these hazards increase the risk of mortality or cancer incidence when compared with the general Czech population.MethodsA cohort of 16 434 male underground miners employed underground for at least 1 year between 1946 and 1976, and alive and residing in the Czech Republic in 1977, were followed for mortality and cancer incidence through 1992. We compared observed deaths and cancer incidence to expectation based on Czech rates. Standardised mortality ratios (SMRs), standardised incidence ratios (SIRs) and causal mortality ratios were calculated.ResultsUnderground workers in the Příbram mines had higher rates of death than expected due to all causes (SMR=1.23, 95% CI 1.20 to 1.27), all cancers (SMR=1.52, 95% CI 1.44 to 1.60), lung cancer (SMR=2.12, 95% CI 1.96 to 2.28) and extrathoracic cancer (SMR=1.41, 95% CI 1.15 to 1.77). Similar excess was observed in cancer incidence analyses, with the addition of stomach cancer (SIR=1.37, 95% CI 1.11 to 1.63), liver cancer (SIR=1.70, 95% CI 1.16 to 2.25) and rectal cancer (SIR=1.41, 95% CI 1.16 to 1.66). The SIR was elevated for all leukaemias (SIR=1.51, 95% CI 1.08 to 2.07) and for lymphatic and haematopoietic cancers combined (SIR=1.31, 95% CI 1.05 to 1.61), but results for specific subtypes were imprecise. Deaths due to hazardous mining conditions resulted in 0.33 person-years of life lost per miner.ConclusionsOccupational exposure to the Příbram mines resulted in excess cancers at several sites, including sites previously linked to radon and uranium exposure. Incidence analyses showed relative excess of several additional cancer subtypes.
Ability of a bovine transrectal palpation objective structured clinical examination to predict veterinary students’ pregnancy diagnosis accuracy
Authors: Annandale Annett , Fosgate Geoffrey T , Bok Harold , Holm Dietmar E 
Published: June 2019

Bovine pregnancy diagnosis (PD) by transrectal palpation (TRP) is one of the most frequently performed procedures in bovine practice, and an important competency for veterinary graduates. It is currently not known if pre‐existing TRP skills on non‐pregnant cows can be used to predict students’ future PD accuracy. The study objective was to evaluate if TRP objective structured clinical examination (OSCE) scores can predict students’ future PD accuracy.Fourth year (of a six‐year programme) veterinary students (n=128) received TRP and PD training on Breed'n Betsy (BB) simulators and live cows. Students’ TRP skills were assessed using a live cow TRP OSCE after completion of the fourth year training. The same students received additional TRP (BB and live cows) and PD (BB) training sessions in the first semester of their fifth year. PD accuracy was assessed after the additional TRP and PD training, five months after the TRP OSCE assessment and measured as sensitivity and specificity (the ability to correctly identify the presence and absence of pregnancy, respectively). Each student palpated six cows transrectally to diagnose pregnancy status and stage for the PD assessment. The TRP OSCE results were analysed as predictors for students’ PD accuracy.Students with ‘competent palpation skills’ on the TRP OSCE had higher PD specificity. The individual OSCE components that were predictive of higher PD accuracy were students’ ability to estimate ovarian size, identify uterine position and exclude intrauterine fluid. It was concluded that a TRP OSCE has the ability to predict students’ future PD accuracy.
Prevalence of and risk factors for acute laminitis in horses treated with corticosteroids
Authors: Potter Katya , Stevens Kim , Menzies‐Gow Nicola 
Published: June 2019

A retrospective treated versus untreated study (study 1) and multicentre prospective cohort study (study 2) were undertaken to determine the prevalence of, and risk factors associated with, acute laminitis in horses treated with corticosteroids. All old treated with corticosteroids January–December 2014 (study 1) and January 2015–February 2017 (study 2) by two first opinion and referral hospitals in UK were included. Additionally, an untreated animal was identified for each treated animal (study one). Signalment, body condition (study 2 only), relevant medical history, primary condition, corticosteroid therapy prescribed and occurrence of acute laminitis during or within 14 days of cessation of corticosteroid treatment were recorded.For study 1, 205 cases and 205 controls were identified; two animals within each group (1 per cent) developed laminitis. In total, 1565 animals were included in study 2; laminitis period prevalence was 0.6 per cent (95 per cent CI 0.4 per cent to 1.2 per cent), with 10 cases in 1565 treated animals. There were significant associations between laminitis and breed (pony vs horse; p=0.01; univariable analysis only), the presence of a laminitis risk factor (history of laminitis or an underlying endocrinopathy; p<0.001; OR (95 per cent CI) 18.23 (5.05 to 65.87)) and body condition (overweight/obese vs not; p=0.04; OR (95 per cent CI) 4.0 (1.09 to 14.75)).
Clinical Genomic Sequencing of Pediatric and Adult Osteosarcoma Reveals Distinct Molecular Subsets with Potentially Targetable Alterations
Authors: Suehara Yoshiyuki , Alex Deepu , Bowman Anita , Middha Sumit , Zehir Ahmet , Chakravarty Debyani , Wang Lu , Jour George , Nafa Khedoudja , Hayashi Takuo , Jungbluth Achim A. , Frosina Denise , Slotkin Emily , Shukla Neerav , Meyers Paul , Healey John H. , Hameed Meera , Ladanyi Marc 
Published: June 2019

Abstract

Purpose:
Although multimodal chemotherapy has improved outcomes for patients with osteosarcoma, the prognosis for patients who present with metastatic and/or recurrent disease remains poor. In this study, we sought to define how often clinical genomic sequencing of osteosarcoma samples could identify potentially actionable alterations.
Experimental Design: We analyzed genomic data from 71 osteosarcoma samples from 66 pediatric and adult patients sequenced using MSK-IMPACT, a hybridization capture-based large panel next-generation sequencing assay. Potentially actionable genetic events were categorized according to the OncoKB precision oncology knowledge base, of which levels 1 to 3 were considered clinically actionable.

Results:
We found at least one potentially actionable alteration in 14 of 66 patients (21%), including amplification of CDK4 (n = 9, 14%: level 2B) and/or MDM2 (n = 9, 14%: level 3B), and somatic truncating mutations/deletions in BRCA2 (n = 3, 5%: level 2B) and PTCH1 (n = 1, level 3B). In addition, we observed mutually exclusive patterns of alterations suggesting distinct biological subsets defined by gains at 4q12 and 6p12-21. Specifically, potentially targetable gene amplifications at 4q12 involving KIT, KDR, and PDGFRA were identified in 13 of 66 patients (20%), which showed strong PDGFRA expression by IHC. In another largely nonoverlapping subset of 14 patients (24%) with gains at 6p12-21, VEGFA amplification was identified.

Conclusions:
We found potentially clinically actionable alterations in approximately 21% of patients with osteosarcoma. In addition, at least 40% of patients have tumors harboring PDGFRA or VEGFA amplification, representing candidate subsets for clinical evaluation of additional therapeutic options. We propose a new genomically based algorithm for directing patients with osteosarcoma to clinical trial options.
Three-Dimensional Nanoscale Nuclear Architecture Mapping of Rectal Biopsies Detects Colorectal Neoplasia in Patients with Inflammatory Bowel Disease
Authors: Uttam Shikhar , Hashash Jana G. , LaFace Justin , Binion David , Regueiro Miguel , Hartman Douglas J. , Brand Randall E. , Liu Yang 
Published: June 2019

Abstract
Patients with inflammatory bowel disease (IBD) colitis are at an increased risk of developing colorectal cancer and are currently recommended to undergo extensive annual or biennial colonoscopy, a costly and invasive procedure. Most surveillance colonoscopies are negative with no existing objective measures for assessing their risk of developing cancer. We have recently developed a less invasive, cost-effective and objective method to assess cancer risk by detecting the presence of colonic neoplasia via 3-dimensional (3D) nanoscale nuclear architecture mapping (nanoNAM) of normal-appearing rectal biopsies. To establish its translational relevance, we prospectively recruited 103 patients with IBD colitis undergoing surveillance colonoscopy and measured submicroscopic alterations in aberrant intrinsic nuclear architecture of epithelial cells from normal-appearing rectal biopsies with nanoNAM. The results were correlated with the histologic diagnoses from all random biopsies obtained during initial and follow-up colonoscopy within 3 years. Using nanoNAM-based structural characterization as input features into a soft margin–based ν-SVM risk classifier, we show that nanoNAM detects colonic neoplasia with AUC of 0.87 ± 0.04, sensitivity of 0.81 ± 0.09, and specificity of 0.82 ± 0.07 in the independent validation set. In addition, projecting nanoNAM features onto a 2-sphere reveals patients with low-risk and high-risk IBD colitis existing on separate hemispheres. Finally, we show that this ability to assess cancer risk translates to clinically-relevant estimation of individual-patient likelihood of being truly at risk. We demonstrate the potential of nanoNAM to identify patients with IBD at higher risk of developing cancer from normal-appearing rectum tissue, which may aid clinicians in patients with personalized IBD colitis surveillance.
Mushroom Consumption and Risk of Total and Site-Specific Cancer in Two Large U.S. Prospective Cohorts
Authors: Lee Dong Hoon , Yang Meng , Keum NaNa , Giovannucci Edward L. , Sun Qi , Chavarro Jorge E. 
Published: June 2019

Abstract
Several case–control studies have reported that mushroom consumption may be associated with reduced risk of certain cancers. However, epidemiologic studies have not yet prospectively examined the association of mushroom consumption with total and various site-specific cancer risks. This prospective cohort study included 68,327 women (Nurses' Health Study, 1986–2012) and 44,664 men (Health Professionals Follow-up Study, 1986–2012) who were free of cancer at baseline. Mushroom consumption was assessed at baseline using a validated food frequency questionnaire. Covariates were assessed using biennial questionnaires during the follow-up. We used Cox proportional hazards models to estimate hazard ratios (HR) and 95% confidence intervals (CI) of total and 17 site-specific cancers associated with mushroom consumption. During up to 26 years of follow-up, we documented 22,469 incident cancer cases (15,103 in women and 7,366 in men). In the pooled multivariable analysis, participants who consumed five or more servings of mushrooms per week had no significantly different risk of total cancer (HR, 1.06; 95% CI, 0.98–1.14) than participants who almost never consumed mushrooms. We consistently found no association between mushroom consumption and risk of 16 site-specific cancers. However, there was a marginal positive association between mushroom consumption and risk of lung cancer (Ptrend = 0.05). In conclusion, we found no association between mushroom consumption and total and site-specific cancers in U.S. women and men. More prospective cohort studies are needed to examine the associations for specific cancer types in diverse racial/ethnic groups.
Sistema aquífero Alter do Chão a oeste da cidade de Manaus (AM): processos hidrogeoquímicos, origem da salinidade e relações com aquíferos adjacentes
Authors: Pita Renato Cosme dos Santos , Silva Júnior Gerson Cardoso da , Rosário Fátima Ferreira do , Silva Márcio Luiz da 
Published: June 2019

O aquífero associado à Formação Alter do Chão (FAC) — subsistema aquífero Alter do Chão (AAC) — é o mais conhecido da região amazônica. Estudos recentes indicam sua possível conexão com o subsistema aquífero cretáceo Tikuna, que possui continuidade por todas as bacias amazônicas, ambos integrando o grande Sistema Aquífero Amazônico (SAA). O objetivo do presente trabalho foi o aperfeiçoamento do modelo conceitual de funcionamento do AAC a oeste de Manaus. A metodologia incluiu medidas do nível d’água, de parâmetros físico-químicos in situ em poços e amostragem para análises químicas e isotópicas das águas subterrâneas. Realizou-se o levantamento das características geológicas e limites do aquífero, baseado em dados de poços de petróleo e de abastecimento de água existentes. Os resultados revelaram que as águas do AAC a oeste de Manaus possuem duas origens principais: 1) origem meteórica, pouco mineralizadas, situadas nas camadas aquíferas superiores, em um sistema livre, com recarga local; 2) origem remota, mais mineralizadas, com maior tempo de residência no aquífero, armazenadas nas camadas mais profundas em um sistema provavelmente confinado, originadas possivelmente em áreas de recarga do bordo oeste do SAA. As análises isotópicas calibradas sugerem uma idade média de 21.380 anos para águas subterrâneas mais mineralizadas e profundas dos municípios de Manacapuru e Careiro. Essa água é, provavelmente, resultado de uma mescla de águas mais antigas com águas de recarga mais recente. Por conta dessa diferenciação hidrogeoquímica, correlacionada com a geologia local, o AAC foi subdividido em uma porção superior, livre e menos mineralizada, e outra inferior, mais antiga e mineralizada, ambas misturadas a leste do Arco de Purus, com progressiva diluição pela chuva.
The Messianic Kingship of Augustin Bader as Anti-Habsburg Polemic: Prophecy and Politics in Reformation Germany
Authors: Bast Robert 
Published: June 2019

Abstract
This paper explores the genesis, self-understanding and significance of a small messianic commune operating in the late 1520s in southern Germany under the headship of Augustin Bader, an Augsburg weaver and erstwhile Anabaptist. It traces the unique convergence of Christian and Jewish messianic expectation in the 1520s that unexpectedly linked Bader to the kabbalistic prognostications of Abraham Halevi and the pseudo-military campaign of David Reuveni. Finally, it argues that Bader’s messianism was specifically crafted as a counter-hegemonic measure against the Habsburgs, whose persecution of Anabaptists such as Bader and his associates made a mockery of that dynasty’s heavy reliance on the imperial messianic ideology of the Last World Emperor.
Life in the Egyptian Valley under Ikhshīdid and Fāṭimid Rule: Insights from Documentary Sources
Authors: Livingston Daisy 
Published: June 2019

Abstract
Offering a micro-historical reading of extant legal deeds from Ashmūnayn in Upper Egypt, this article investigates the history of the diverse communities living in the Egyptian valley during the Ikhshīdid and Fāṭimid periods. It reveals the varied nature of settlements, the large extent of interconnections between towns and villages of different size and character, and the implications these had on legal and documentary practice. It presents a re-evaluated concept of centres and peripheries within the context of the Egyptian valley which highlights the varied pace at which developments taking place in central areas impacted on more remote regions, and argues for an understanding of the history of the Egyptian valley that looks beyond periodisation based on dynastic change.
A Hymn to God Assigned to Gregory of Nazianzus and Its Neoplatonic Context
Authors: Timotin Andrei 
Published: June 2019

AbstractThe paper deals with an anonymous Hymn to God, which is attributed to Gregory of Nazianzus by some authors, but was most probably composed by a Christian Neoplatonist such as Pseudo-Dionysius the Areopagite. The paper explores the hymn’s relation to Neoplatonic theories of prayer and shows that these affinities are broader in scope than has previously been recognised. Some Pagan and Christian Neoplatonists, including the author of the Hymn to God, seem to have shared the idea of a cosmic prayer by which all beings tend towards God, a prayer founded on the knowledge of the ‘signatures’ (synthemata) that God rooted in our souls.
Thou Shalt Not Enter the Bazaar on Rainy Days! Zemmi Merchants in Safavid Isfahan: Shiʿite Feqh Meeting Social Reality
Authors: Kiyanrad Sarah 
Published: June 2019

Abstract
Many Muslim and non-Muslim merchants from East and West were attracted to Safavid Isfahan, the new “center of the world,” a city that also played host to its own mercantile communities, among them many zemmi traders—Christians, Jews, and Zoroastrians. As representatives of the newly-established Twelver Shiʿite theology, Safavid religious scholars felt the need to offer commentary on evolving issues on a theoretical level, sometimes writing not in Arabic but in New Persian. How did they regard the activities of zemmi merchants? Were zemmi traders subject to religiously-motivated restrictions? Or did they, on the other hand, enjoy exclusive rights? While my paper focusses on these questions, it will also compare the legal opinions of selected Safavid foqahāʾ on the social reality as reflected in travelogues and through historiography.