bluuebunny/crossref_metadata_2025_split huggingface dataset:
Treating Hernias in Ottoman Crete (c. 1670–1760): The Legal Imprint of a Medical Procedure
Authors: Anastasopoulos Antonis , Kyriakopoulos Christos 
Published: May 2019

Summary
In Crete, as in the rest of the Ottoman Empire, patients who suffered from hernias and other diseases that required surgery made statements to the court of law that absolved the surgeons of liability in case of death as a result of the operation. These statements also included information about the medical condition concerned, the surgeon, the medical procedure and the fee to be paid. In this article, we discuss such statements of the period 1670–1760 from the town of Kandiye (mod. Heraklion). On one hand, we demonstrate that a critical analysis of the statements reveals a dynamic society, which actively overcomes its ideology of submission to God and religious prejudices when it comes to dealing with health issues. On the other hand, we argue that, as the statements were made before the official court of law, they constitute a facet of the Ottomanisation of Cretan society and its practices.
Defining Hospital Catchment Areas Using Multiscale Community Detection: A Case Study for Planned Orthopaedic Care in England
Authors: Clarke Jonathan M , Barahona Mauricio , Darzi Ara W 
Published: May 2019

AbstractBackgroundThe English National Health Service 5-year Forward View emphasises the importance of integration of hospital and community services. Understanding the population a hospital serves is critical to formulating strategies for community engagement and determining their accountability for populations. Existing methods to define catchment areas are unable to adapt to dilute health care markets in urban areas where populations may interact with several different hospitals. Formulating catchment areas which permit the inclusion of more than one hospital based upon patient behaviour allows for collaboration between hospitals to reach out into the communities they collectively share.MethodThe proportion of presentations from all census Middle Super Output Areas (MSOAs) to every hospital trust providing orthopaedic care in England were calculated. The cosine similarity of all MSOAs to one another was computed from these proportions. Multiscale community detection was applied to planned orthopaedic surgical admissions in England from 1st April 2011 to 31st March 2015. Stable community configurations were identified and the proportion of patients presenting to hospitals located within the catchment area in which they resided was calculated. The performance of these catchment areas was compared to conventional methods for assigning mutually exclusive catchment areas.Results2,602,066 planned orthopaedic surgical admissions were identified for patients resident in 6,791 MSOAs in England attending 140 different hospital trusts. Markov multiscale community detection revealed five stable catchment area configurations consisting of 127, 51, 26, 15 and 11 catchment areas. Between 78% (127 catchments) and 93% (11 catchments) of clinical presentations were to hospitals within a patient’s allocated catchment area compared to 76% for the “first past the post” method.ConclusionsMultiscale community detection is a novel and effective, data-driven method for defining mutually exclusive, collectively exhaustive catchment areas in secondary care. In urban areas with dilute healthcare markets, the model favours collaboration between hospitals in covering a clearly delineated but shared catchment, and thereby produces simplified and more representative catchment areas.
Structural integrity following focused ultrasound thalamotomy and its correlation with tremor relief
Authors: Zur Gil , Lesman-Segev Orit , Schlesinger Ilana , Goldsher Dorith , Sinai Alon , Zaaroor Menashe , Assaf Yaniv , Eran Ayelet , Kahn Itamar 
Published: May 2019

AbstractBackgroundMagnetic-resonance-guided focused ultrasound ablation of ventral intermediate nucleus of the thalamus is a new treatment for tremor disorders.ObjectivesWe sought to evaluate the white matter integrity prior to and following focused ultrasound ablation and its correlation with clinical outcome.Methods22 patients with essential tremor and 17 patients with Parkinson’s disease underwent tremor and quality-of-life assessments prior to and at one and six months following focused ultrasound ablation. All patients underwent MRI including T1, T2-FLAIR and diffusion weighted imaging before treatment and at one day, 7–10 days, 1–3 months, and 6 months or more following it. Diffusivity parameters were calculated and fiber tractography measures were extracted. Change in diffusivity parameters were assessed inside the ablated core, in the motor thalamus and throughout the dentato-rubro-thalamo-cortical tract.ResultsWe found short-term changes in the motor thalamus and in the tract between the thalamus and regions within the dentato-rubro-thalamo-cortical tract. Long term damage was found in the ablated core and in the tract connecting the thalamus and red-nucleus. Inverse correlation was found between fractional anisotropy in the motor thalamus one day following ablation and tremor improvement in both patient groups, with lower values before treatment associated with better outcome (tremor relief) in essential tremor patients.ConclusionsShort-and long-term changes in white matter integrity are present following focused ultrasound thalamotomy. Regions demonstrating long-term white matter changes may be responsible for the tremor relief seen in patients, implicating these regions in the disorder’s pathogenesis.
Genome-wide association study of plasma triglycerides, phospholipids and relation to cardio-metabolic risk factors
Authors: Demirkan Ayşe , Pool Rene , Deelen Joris , Beekman Marian , Liu Jun , Harms Amy C. , Vaarhorst Anika , Hagenbeek Fiona A , Willemsen Gonneke , Verhoeven Aswin , Amin Najaf , van Dijk Ko Willems , Hankemeier Thomas , Boomsma Dorret I. , Slagboom Eline , van Duijn Cornelia M. 
Published: May 2019

AbstractThere is continuous interest in the genetic determinants of plasma triglycerides (TGs) and phospholipids and their role in the etiology of cardiovascular disease (CVD). Here, we report the results of a Dutch genome wide association study (GWAS) of an in-house developed lipidomics platform, focusing on 90 plasma lipids. Lipids were assessed by liquid chromatography mass spectrometry in participants from the Leiden Longevity Study, the Netherlands Twin Register and the Erasmus Rucphen Family (ERF) study and meta-analysed, resulting in a sample size of 5537 participants. In addition, we performed genetic correlation analyses between the 90 plasma lipids and markers of metabolic health, as well as vascular pathology and CVD combining our GWAS results with publicly available GWAS outputs. We replicated previously known associations between 34 lipids and 10 lipid quantitative trait loci (lipQTL) (GCKR, APOA1, FADS1, SGPP1,TMEM229B, LIPC, PDXDC1, CETP, CERS4andSPTLC3) with metabolome-wide (P < 1.61 × 10−9) significance. Moreover, we report 6 novel phospholipid-related and 5 triglyceride (TG)-related loci:SGGP1(SM21:0),SPTLC3(SM21:0 and SM25:1),FADS1(LPCO16:1, PC38:2, PEO36:5, PEO38:5, TG56:5, TG56:6, and TG56:7),TMEM229(LPCO16:1),GCKR(TG50:2), andAPOA1(TG54:4). In addition, we report suggestively significant (P < 5 × 10−8) associations mapping to eleven novel lipid quantitative trait loci (lipQTLs), three of which are supported by mining previous GWAS data:MAU(PC34:4),LDLR(SM16:0), andMLXIPL(TG48:1 and TG50:1)). Genetic correlation analysis indicates that one specific specific sphingomyelin, SM22:0, shares common genetic background with CVD. Levels of SM22:0 also positively associate with carotid artery intima-media thickness in the ERF study, and this observation is independent of LDL-C level. Our findings yield higher resolution of plasma lipid species and new insights in the biology of circulating phosholipids and their relation to CVD risk.
The effect of number of healthcare visits on study sample selection and prevalence estimates in electronic health record data
Authors: Rasmussen-Torvik Laura J. , Furmanchuk Al’ona , Stoddard Alexander J. , Osinski Kristen I. , Meurer John R. , Smith Nicholas , Chrischilles Elizabeth , Black Bernard S. , Kho Abel 
Published: May 2019

AbstractIntroductionFew studies have addressed how to select a study sample when using electronic health record (EHR) data.MethodsYear 2016 EHR data from three health systems was used to examine how alternate definitions of the study sample, based on number of healthcare visits in one year, affected measures of disease period prevalence. Curated collections of ICD-9, ICD-10, and SNOMED codes were used to define three diseases.ResultsAcross all health systems, increasing the minimum required number of visits to be included in the study sample monotonically increased crude period prevalence estimates. The rate at which prevalence estimates increased with number of visits varied across sites and across diseases.ConclusionsWhen using EHR data authors must carefully describe how a study sample is identified and report outcomes for a range of sample definitions, so that others can assess the sensitivity of reported results to sample definition in EHR data.
Genomic and physiological analyses reveal that extremely thermophilicCaldicellulosiruptor changbaiensisdeploys unique cellulose attachment mechanisms
Authors: Khan Asma M.A.M. , Mendoza Carl , Hauk Valerie J. , Blumer-Schuette Sara E. 
Published: May 2019

ABSTRACTThe genusCaldicellulosiruptorare extremely thermophilic, heterotrophic anaerobes that degrade plant biomass using modular, multifunctional enzymes. Prior pangenome analyses determined that this genus is genetically diverse, with the current pangenome remaining open, meaning that new genes are expected with each additional genome sequence added. Given the high biodiversity observed among the genusCaldicellulosiruptor, we have sequenced and added a 14thspecies,Caldicellulosiruptor changbaiensis, to the pangenome. The pangenome now includes 3,791 ortholog clusters, 120 of which are unique toC. changbaiensisand may be involved in plant biomass degradation. Comparisons betweenC. changbaiensisandCaldicellulosiruptor besciion the basis of growth kinetics, cellulose solubilization and cell attachment to polysaccharides highlighted physiological differences between the two species which are supported by their respective gene inventories. Most significantly, these comparisons indicated thatC. changbaiensispossesses unique cellulose attachment mechanisms not observed among the other strongly cellulolytic members of the genusCaldicellulosiruptor.
In vivomicrostructural heterogeneity of white matter lesions in Alzheimer’s disease using tissue compositional analysis of diffusion MRI data
Authors: Mito Remika , Dhollander Thijs , Xia Ying , Raffelt David , Salvado Olivier , Churilov Leonid , Rowe Christopher C , Brodtmann Amy , Villemagne Victor L , Connelly Alan 
Published: May 2019

AbstractWhite matter hyperintensities (WMH) are commonly observed in elderly individuals, and are typically more prevalent in Alzheimer’s disease subjects than in healthy subjects. These lesions can be identified on fluid attenuated inversion recovery (FLAIR) MRI, on which they are hyperintense compared to their surroundings. These MRI-visible lesions appear homogeneously hyperintense despite known heterogeneity in their pathological underpinnings, and are commonly regarded as surrogate markers of small vessel disease inin vivostudies. Consequently, the extent to which these lesions contribute to Alzheimer’s disease remains unclear, likely due to the somewhat limited way in which these lesions are assessedin vivo. Diffusion MRI is sensitive to white matter microstructure, and might thus be used to investigate microstructural changes within WMH. In this study, we applied a method called single-shell 3-tissue constrained spherical deconvolution, which models white matter microstructure while also accounting for other tissue compartments, to investigate WMHin vivo. Diffusion MRI data and FLAIR images were obtained from Alzheimer’s disease (n= 48) and healthy elderly control (n= 94) subjects from the Australian Imaging, Biomarkers and Lifestyle study of ageing. WMH were automatically segmented and classified as periventricular or deep lesions from FLAIR images based on their continuity with the lateral ventricles, and the 3-tissue profile of different classes of WMH was characterised by three metrics, which together characterised the relative tissue profile in terms of the white matter-, grey matter-, and fluid-like characteristics of the diffusion signal. Our findings revealed that periventricular and deep lesion classes could be distinguished from one another, and from normal-appearing white matter based on their 3-tissue profile, with substantially higher free water content in periventricular lesions than deep. Given the higher lesion load of periventricular lesions in Alzheimer’s disease patients, the 3-tissue profile of these WMH could be interpreted as reflecting the more deleterious pathological underpinnings that are associated with disease. However, when alternatively classifying lesion sub-regions in terms of distance contours from the ventricles to account for potential heterogeneity within confluent lesions, we found that the highest fluid content was present in lesion areas most proximal to the ventricles, which were common to both Alzheimer’s disease subjects and healthy controls. We argue that whatever classification scheme is used when investigating WMH, failure to account for heterogeneity within lesions may result in classification-scheme dependent conclusions. Future studies of WMH in Alzheimer’s Disease would benefit from inclusion of microstructural information when characterising lesions.
Mitochondrial glycerol phosphate oxidation is modulated by adenylates through allosteric regulation of cytochromecoxidase activity in mosquito flight muscle
Authors: Gaviraghi Alessandro , Correa Soares Juliana B.R. , Mignaco Julio A. , L. Fontes Carlos Frederico , Oliveira Marcus F. 
Published: May 2019

AbstractThe huge energy demand posed by insect flight activity is met by an efficient oxidative phosphorylation process that takes place within flight muscle mitochondria. In the major arbovirus vectorAedes aegypti, mitochondrial oxidation of pyruvate, proline and glycerol 3 phosphate (G3P) represent the major energy sources of ATP to sustain flight muscle energy demand. Although adenylates exert critical regulatory effects on several mitochondrial enzyme activities, the potential consequences of altered adenylate levels to G3P oxidation remains to be determined. Here, we report that mitochondrial G3P oxidation is controlled by adenylates through allosteric regulation of cytochrome c oxidase (COX) activity inA. aegyptiflight muscle. We observed that ADP significantly activated respiratory rates linked to G3P oxidation, in a protonmotive force-independent manner. Kinetic analyses revealed that ADP activates respiration through a slightly cooperative mechanism. Despite adenylates caused no effects on G3P-cytochromecoxidoreductase activity, COX activity was allosterically activated by ADP. Conversely, ATP exerted powerful inhibitory effects on respiratory rates linked to G3P oxidation and on COX activity. We also observed that high energy phosphate recycling mechanisms did not contribute to the regulatory effects of adenylates on COX activity or G3P oxidation. We conclude that mitochondrial G3P oxidation byA. aegyptiflight muscle is regulated by adenylates essentially through the allosteric modulation of COX activity, underscoring the bioenergetic relevance of this novel mechanism and the potential consequences for mosquito dispersal.
Parsing out the variability of transmission at central synapses using optical quantal analysis
Authors: Soares Cary , Trotter Daniel , Longtin André , Béïque Jean-Claude , Naud Richard 
Published: May 2019

ABSTRACTProperties of synaptic release dictates the core of information transfer in neural circuits. Despite decades of technical and theoretical advances, distinguishing bona fide information content from the multiple sources of synaptic variability remains a challenging problem. Here, we employed a combination of computational approaches with cellular electrophysiology, two-photon uncaging of MNI-Glutamate and imaging at single synapses. We describe and calibrate the use of the fluorescent glutamate sensor iGluSnFR and found that its kinetic profile is close to that of AMPA receptors, therefore providing several distinct advantages over slower methods relying on NMDA receptor activation (i.e., chemical or genetically encoded Calcium indicators). Using an array of statistical methods, we further developed, and validated on surrogate data, an expectation-maximization algorithm that, by biophysically constraining release variability, extracts the quantal parameters n (maximum number of released vesicles) and p (unitary probability of release) from single-synapse iGluSnFR-mediated transients. Together, we present a generalizable mathematical formalism which, when applied to optical recordings, paves the way to an increasingly precise investigation of information transfer at central synapses.
Single cell transcriptomics reveals involution mimicry during the specification of the basal breast cancer subtype
Authors: Valdes-Mora Fatima , Salomon Robert , Gloss Brian , Law Andrew MK. , Castillo Lesley , Murphy Kendelle J. , Venhuizen Jeron , Magenau Astrid , Papanicolau Michael , de la Fuente Laura Rodriguez , Roden Daniel L. , Colino-Sanguino Yolanda , Kikhtyak Zoya , Farbehi Nona , Conway James RW. , Oakes Samantha R. , Sikta Neblina , O’Donoghue Seán I. , Cox Thomas R , Timpson Paul , Ormandy Christopher J. , Gallego-Ortega David 
Published: May 2019

AbstractBoth luminal and basal breast cancer subtypes originate in the mammary luminal progenitor cell compartment. Basal breast cancer is associated with younger age, early relapse, and high mortality rate. Here we used unbiased droplet-based single-cell RNAseq to elucidate the cellular basis of tumour progression during the specification of the basal breast cancer subtype from the luminal progenitor population. Basal–like cancer cells resembled the alveolar lineage that is specified upon pregnancy and showed molecular features indicative of an interaction with the tumour microenvironment (TME) including epithelial-to-mesenchymal transition (EMT), hypoxia, lactation and involution. Involution signatures in luminal breast cancer tumours with alveolar lineage features were associated with worse prognosis and features of basal breast cancer. Our high-resolution molecular characterisation of the tumour ecosystem also revealed a highly interactive cell-cell network reminiscent of an involution process. This involution mimicry involves malignant education of cancer-associated fibroblasts and myeloid cell recruitment to support tissue remodelling and sustained inflammation. Our study shows how luminal breast cancer acquires an aberrant post-lactation developmental program that involves both cancer cells and cells from the TME, to shift molecular subtype and promote tumour progression, with potential to explain the increased risk and poor prognosis of breast cancer associated to childbirth.
Reassessing the Evidence for Universal School-age Bacillus Calmette Guerin (BCG) Vaccination in England and Wales
Authors: Abbott Sam , Christensen Hannah , Brooks-Pollock Ellen 
Published: May 2019

AbstractBackgroundIn 2005, England and Wales switched from universal BCG vaccination against tuberculosis (TB) disease for school-age children to targeted vaccination of neonates. We assessed the quantitative evidence that informed this policy change.MethodsWe recreated a previous approach for estimating the impact of ending the BCG schools’ scheme in England and Wales, updating the model with parameter uncertainty. We investigated scenarios considered by the UK’s Joint Committee on Vaccination and Immunisation, and explored new approaches using notification data. We estimated the number of vaccines needed to prevent a single notification, and the average annual additional notifications caused by ending the BCG schools’ scheme.ResultsWe found a 1.9% annual decrease in TB incidence rates best matched notification data. We estimate that 1600 (2.5-97.5% Quantiles (Q): 1300 - 2100) vaccines would have been required to prevent a single notification in 2004. If the scheme had ended in 2001, 302 (2.5-97.5% Q: 238 - 369) additional annual notifications would have occurred compared to if the scheme had continued. If the scheme ended in 2016, 120 (2.5-97.5% Q: 88 - 155) additional annual notifications would have occurred.ConclusionsOur estimates of the impact of ending the BCG schools’ scheme were highly sensitive to the annual decrease in incidence rates. The impact of ending the BCG schools’ scheme was found to be greater than previously thought when parameter values were updated and notification data were used. Our results highlight the importance of including uncertainty when forecasting the impact of changes in vaccination policy.What is already known on this subjectTargeted Bacillus Calmette Guerin (BCG) vaccination against TB is recommended in low incidence countries over universal vaccination.The impact of replacing universal BCG vaccination in England and Wales with a targeted programme in 2005 was assessed under the assumption of static declines in TB rates.The BCG Guerin vaccine was shown to be effective in the UK born in England, regardless of the age at which it was given. School-age vaccination maybe more beneficial in this population than in other settings.What this study addsUsing notification data from England and Wales from 1973 to 2015, we estimate that the ending the BCG schools’ scheme likely resulted in more additional cases than was predicted.The inclusion of parameter uncertainty, and measurement error, allowed the uncertainty in the final estimates to be presented. Previously published estimates may have been spuriously precise.This study highlights the need for a more detailed evaluation of the 2005 change in BCG policy. In particular, the impact of including the introduction of targeted neonatal vaccination and capturing the long term, indirect, effects needs further study.
Triphenyl phosphate is a selective PPARγ modulator that does not induce brite adipogenesis in vitro and in vivo
Authors: Kim Stephanie , Rabhi Nabil , Blum Benjamin C. , Hekman Ryan , Wynne Kieran , Emili Andrew , Farmer Stephen , Schlezinger Jennifer J. 
Published: May 2019

AbstractTriphenyl phosphate (TPhP) is an environmental PPARγ ligand, and growing evidence suggests that it is a metabolic disruptor. We have shown previously that the structurally similar ligand, tributyltin, does not induce brite adipocyte gene expression. Here, using in vivo and in vitro models, we tested the hypothesis that TPhP is a selective PPARγ ligand, which fails to induce brite adipogenesis. C57BL/6J male mice were fed either a low or very high fat diet for 13 weeks. From weeks 7-13, mice were injected intraperitoneally, daily, with vehicle, rosiglitazone (Rosi), or TPhP (10 mg/kg). Compared to Rosi, TPhP did not induce expression of browning-related genes (e.g. Elovl3, Cidea, Acaa2, CoxIV) in mature adipocytes isolated from inguinal adipose. To determine if this resulted from an effect directly on the adipocytes, 3T3-L1 cells and primary human preadipocytes were differentiated into adipocytes in the presence of Rosi or TPhP. Rosi, but not TPhP, induced expression of brite adipocyte genes, mitochondrial biogenesis and cellular respiration. Further, Rosi and TPhP induced distinct proteomes and phosphoproteomes; Rosi enriched more regulatory pathways related to fatty acid oxidation and mitochondrial proteins. We assessed the role of phosphorylation of PPARγ in these differences in 3T3-L1 cells. Only Rosi protected PPARγ from phosphorylation at Ser273. TPhP gained the ability to stimulate brite adipocyte gene expression in the presence of the CDK5 inhibitor and in 3T3-L1 cells expressing alanine at position 273. We conclude that TPhP is a selective PPARγ modulator that fails to protect PPARγ from phosphorylation at ser273.