bluuebunny/crossref_metadata_2025_split huggingface dataset:
Hyperosmolar environment and salivary gland epithelial cells increase extra-cellular matrix remodeling and lymphocytic infiltration in Sjögren’s syndrome
Authors: Rivière Elodie , Chivasso Clara , Pascaud Juliette , Bechara Rami , Ly Bineta , Delporte Christine , Mariette Xavier , Nocturne Gaetane 
Published: February 2023

AbstractSalivary gland epithelial cells (SGECs) play an active role in primary Sjogren’s syndrome (pSS) pathogenesis. Quantitative and qualitative abnormalities of saliva might expose SGECs to chronic hyperosmolarity. We aimed to decipher the links between hyperosmolar stimulation of SGECs and lymphocytic infiltration of the salivary glands (SG) observed in pSS. RNAseq was performed on NS-SV-AC cells stimulated with hyperosmolar media containing NaCl (100 mM) or sucrose (200 mM), or with iso-osmolar (Iso) medium. RNAseq was performed on primary cultured SGECs from pSS and controls, in the presence or not of B cells. Hyperosmolar stimulation of NS-SV-AC-cells identified an upregulation of interferon-induced (MX1, IFIT2) and MMPs genes. Enrichment analysis revealed an over-representation of fibrosis pathway. In parallel, RNAseq of SGECs comparing pSS to controls identified an over-representation of a pathway involving MMPs. Given the unexpected upregulation of collagen (COL3A1, COL1A2) and ADAMTS genes in pSS SGECs, we hypothesized that SGECs might undergo epithelial–mesenchymal transition. ZEB2 was upregulated and SLUG was down regulated in SGECs from pSS versus controls. MMP24 and ZEB2 were higher in SGECs from pSS with a focus score ≥1 versus &lt;1. Lastly, SGECs cocultured with B cells expressed higher levels of COL1A2. These results suggest the existence of a vicious circle. Alteration of SGECs in pSS participates in the establishment of a hyperosmolar microenvironment, which in turn promotes SGECs transcriptomic modifications. These modifications include extracellular matrix remodeling and promote SG lymphocytic infiltration.
Examination of common and unique brain regions for atypical reading and math: a meta-analysis
Authors: Martinez-Lincoln Amanda , Fotidzis Tess S , Cutting Laurie E , Price Gavin R , Barquero Laura A 
Published: February 2023

Abstract
The purpose of this study is to identify consistencies across functional neuroimaging studies regarding common and unique brain regions/networks for individuals with reading difficulties (RD) and math difficulties (MD) compared to typically developing (TD) individuals. A systematic search of the literature, utilizing multiple databases, yielded 116 functional magnetic resonance imaging and positron emission tomography studies that met the criteria. Coordinates that directly compared TD with either RD or MD were entered into GingerALE (Brainmap.org). An activation likelihood estimate (ALE) meta-analysis was conducted to examine common and unique brain regions for RD and MD. Overall, more studies examined RD (n = 96) than MD (n = 20). Across studies, overactivation for reading and math occurred in the right insula and inferior frontal gyrus for atypically developing (AD) &gt; TD comparisons, albeit in slightly different areas of these regions; however, inherent threshold variability across imaging studies could diminish overlying regions. For TD &gt; AD comparisons, there were no similar or overlapping brain regions. Results indicate there were domain-specific differences for RD and MD; however, there were some similarities in the ancillary recruitment of executive functioning skills. Theoretical and practical implications for researchers and educators are discussed.
Value of screening for the risk of sudden cardiac death in young competitive athletes
Authors: Sarto Patrizio , Zorzi Alessandro , Merlo Laura , Vessella Teresina , Pegoraro Cinzia , Giorgiano Flaviano , Graziano Francesca , Basso Cristina , Drezner Jonathan A , Corrado Domenico 
Published: February 2023

AbstractAimsThis study aimed to report the long-term findings of the Italian programme of cardiovascular preparticipation screening (PPS) in young, competitive athletes.Methods and resultsThe study assessed the diagnostic yield for diseases at risk of sudden cardiac death (SCD), the costs of serial evaluations, and the long-term outcomes of PPS in a large population of Italian children (age range, 7–18 years). The PPS was repeated annually and included medical history, physical examination, resting electrocardiogram, and stress testing; additional tests were reserved for athletes with abnormal findings. Over an 11-year study period, 22 324 consecutive children [62% males; mean age, 12 (interquartile range, 10–14) years at first screening] underwent a total of 65 397 annual evaluations (median 2.9/child). Cardiovascular diseases at risk of SCD were identified in 69 children (0.3%) and included congenital heart diseases (n = 17), channelopathies (n = 14), cardiomyopathies (n = 15), non-ischaemic left ventricular scar with ventricular arrhythmias (n = 18), and others (n = 5). At-risk cardiovascular diseases were identified over the entire age range and more frequently in children ≥12 years old (n = 63, 91%) and on repeat evaluation (n = 44, 64%). The estimated cost per diagnosis was 73 312€. During a follow-up of 7.5 ± 3.7 years, one child with normal PPS findings experienced an episode of resuscitated cardiac arrest during sports activity (event rate of 0.6/100.000 athletes/year).ConclusionThe PPS programme led to the identification of cardiovascular diseases at risk of SCD over the whole study age range of children and more often on repeat evaluations. Among screened children, the incidence of sport-related cardiac arrest during long-term follow-up was low.
Public perceptions of responsibility for recommended food policies in seven countries
Authors: Pinho-Gomes Ana-Catarina , Booth Leon , Pettigrew Simone 
Published: February 2023

AbstractBackgroundFood policy is important to promote healthy and sustainable diets. However, who is responsible for developing and implementing food policy remains contentious. Therefore, this study aimed to investigate how the public attributes responsibility for food policy to governments, individuals and the private sector.MethodsA total of 7559 respondents from seven countries [Australia (n = 1033), Canada (n = 1079), China (n = 1099), India (n = 1086), New Zealand (n = 1090), the UK (n = 1079) and the USA (n = 1093)] completed an online survey assessing perceived responsibility for 11 recommended food policies.ResultsOverall, preferred responsibility for the assessed food policies was primarily attributed to governments (62%), followed by the private sector (49%) and individuals (31%). Respondents from New Zealand expressed the highest support for government responsibility (70%) and those from the USA the lowest (50%). Respondents from the USA and India were most likely to nominate individuals as responsible (both 37%), while those from China were least likely (23%). The private sector had the highest attributed responsibility in New Zealand (55%) and the lowest in China and the USA (both 47%). Support for government responsibility declined with age and was higher among those on higher incomes, with a university degree, and who perceived themselves to consume a healthy diet or be in poor health.ConclusionsAcross seven diverse countries, results indicate the public considers government should take primary responsibility for the assessed food policies, with modest contribution from the private sector and minority support for individual responsibility.
Regulation of trehalose metabolism in insects: from genes to the metabolite window
Authors: Tellis Meenakshi B , Kotkar Hemlata M , Joshi Rakesh S 
Published: February 2023

AbstractTrehalose is a major circulatory sugar in the haemolymph of insects. It provides instant energy and protection against stress. Trehalose metabolism is associated with insect growth and development. The architecture and spatio-temporal expression dynamics of trehalose metabolism and transport genes are key for regulation. These genes are controlled by various transcription factors, largely linked to nutrition, insect development, and metamorphosis. Also, trehalose levels are affected by substrate affinities and modifications of enzymes involved in the pathway. A feedback mechanism involving the precursors and products can regulate trehalose metabolism. Further, the neuroendocrine system controls trehalose levels under normal and stressed conditions by producing different hormones. Hypotrehalosemic hormones work under surplus energy conditions to activate haemolymph trehalose uptake and degradation. In contrast, hypertrehalosemic hormones stimulate trehalose production in the fat body and its transport to the haemolymph. However, trehalose metabolism regulation in insects needs to be studied in detail. This review discusses aspects of trehalose synthesis, transport, and degradation dynamics in developmental transition and stress response. Unraveling the epigenetic factors, transcriptional control and chemical or genetic modulators can provide further insights into the intricate regulation of trehalose in a development- and tissue-specific manner. This molecular information about effectors and regulators of trehalose metabolism can be applied in developing diverse biotechnological applications.
Varied Patterns of Decay of Intact Human Immunodeficiency Virus Type 1 Proviruses Over 2 Decades of Antiretroviral Therapy
Authors: Gandhi Rajesh T , Bosch Ronald J , Mar Hanna , Laird Gregory M , Halvas Elias K , Hovind Laura , Collier Ann C , Riddler Sharon A , Martin Albine , Ritter Kristen , McMahon Deborah K , Eron Joseph J , Cyktor Joshua C , Mellors John W ,   AIDS Clinical Trials Group A5321 Team, Hogg Evelyn , LeBlanc Rebecca , Scello Christine , Palm David , Gandhi Monica , Fletcher Courtney , Podany Anthony , Aweeka Fran , Joseph Jeymohan , Pederson Susan , Rubin Leah , Smith Davey , Spudich Serena , Tsibris Athe 
Published: February 2023

Abstract
Fourteen people with human immunodeficiency virus type 1 had longitudinal measurements of intact, defective, and total proviral DNA over the course of two decades of antiretroviral therapy. Three patterns of intact proviral DNA decay were revealed: (1) biphasic decline with markedly slower second-phase decline, (2) initial decline that transitions to a zero-slope plateau, and (3) initial decline followed by later increases in intact proviral DNA. Defective proviral DNA levels were essentially stable. Mechanisms of slowing or reversal of second-phase decay of intact proviral DNA may include the inability to clear cells with intact but transcriptionally silent proviruses and clonal expansion of cells with intact proviruses.
The (Dis-)Appearance of Race in the United Kingdom’s Institutionalization and Implementation of the Women, Peace and Security Agenda
Authors: Achilleos-Sarll Columba 
Published: February 2023

Abstract
In contrast to earlier, more celebratory accounts, more recent scholarship on the United Nations Security Council's Women, Peace and Security (WPS) agenda reveals the racial–colonial logics deeply woven into the very fabric of the agenda that contribute to reproducing hierarchies, inequalities, and exclusions. Building on this body of literature, this article investigates in more detail how race shapes the United Kingdom's engagement with and institutionalization of the WPS agenda, reinforcing particular domestic identities. Drawing from a rich body of new empirical material, including documentary sources and interview data, the analysis excavates four interlinked racial–colonial practices: (1) the erasure of Britain's imperial and colonial history; (2) the production of new geographies of empire; (3) the construction of cultural inferiority of the “other”; and (4) nation branding efforts that construct the UK as the repository of leadership and expertise. I argue that the UK serves as an illustrative case that yields significant empirical and theoretical insights regarding how race is central to the institutionalization and implementation of the WPS agenda by national governments in the Global North and how, in turn, the WPS agenda enables those governments to identify as morally and culturally superior, thereby justifying racialized hierarchies in international relations.
Development and validation of a dosing nomogram for continuous infusion cloxacillin in infective endocarditis
Authors: Bellouard Ronan , Rambaud Antoine , Delaunay Clarisse , Dailly Éric , Lecomte Raphaël , Deschanvres Colin , Leroy Anne-Gaëlle , Boutoille David , Le Turnier Paul , Grégoire Matthieu ,   the Nantes Anti-Microbial Agents PK/PD (NAMAP) study group, Boutoille David , Gaborit Benjamin Jean , Le Turnier Paul , Deschanvres Colin , Lecomte Raphaël , Grégoire Matthieu , Bellouard Ronan , Deslandes Guillaume , Dailly Eric , Leroy Anne-Gaëlle , Corvec Stéphane , Morio Florent , Huon Jean-François , Navas Dominique 
Published: February 2023

AbstractBackgroundCloxacillin is the first-line treatment for methicillin-susceptible staphylococcal infective endocarditis (IE). The recommended dose is 12 g per day regardless of the patient characteristics, despite the importance of renal function on its pharmacokinetics.ObjectivesWe sought to build a population pharmacokinetics model of continuous infusion cloxacillin in IE patients to evaluate the influence of multiple covariates and then develop a nomogram based on significant covariates for individual adaptation.Patients and methodsWe included patients of a local IE cohort who were treated with cloxacillin administered by continuous infusion, excluding those who received intermittent or continuous dialysis, extracorporeal membrane oxygenation or extracorporeal circulation. The population pharmacokinetic analysis was performed using Pmetrics. The influence of weight, ideal weight, height, body mass index, body surface area, glomerular filtration rate (GFR) calculated with the Chronic Kidney Disease Epidemiology Collaboration formula (both expressed in mL/min/1.73 m² and in mL/min) and serum protein level on cloxacillin pharmacokinetics was assessed. Accounting for relevant covariates, a dosing nomogram was developed to determine the optimal daily dose required to achieve a steady-state plasma concentration range of 20–50 mg/L with a probability ≥0.9.ResultsA total of 114 patients (331 plasma concentrations) were included. A one-compartment model including GFR expressed in mL/min as a covariate was chosen. Using the nomogram, achieving the cloxacillin concentration target requires a daily dose ranging from 3.5 to 13.1 g for a GFR ranging from 20 to 125 mL/min.ConclusionsThis work provided a practical tool for cloxacillin dose adjustment in IE according to renal function.
A platform for phenotyping disease progression and associated longitudinal risk factors in large-scale EHRs, with application to incident diabetes complications in the UK Biobank
Authors: Kim Do Hyun , Jensen Aubrey , Jones Kelly , Raghavan Sridharan , Phillips Lawrence S , Hung Adriana , Sun Yan V , Li Gang , Reaven Peter , Zhou Hua , Zhou Jin J 
Published: February 2023

Abstract

Objective
Modern healthcare data reflect massive multi-level and multi-scale information collected over many years. The majority of the existing phenotyping algorithms use case–control definitions of disease. This paper aims to study the time to disease onset and progression and identify the time-varying risk factors that drive them.

Materials and Methods
We developed an algorithmic approach to phenotyping the incidence of diseases by consolidating data sources from the UK Biobank (UKB), including primary care electronic health records (EHRs). We focused on defining events, event dates, and their censoring time, including relevant terms and existing phenotypes, excluding generic, rare, or semantically distant terms, forward-mapping terminology terms, and expert review. We applied our approach to phenotyping diabetes complications, including a composite cardiovascular disease (CVD) outcome, diabetic kidney disease (DKD), and diabetic retinopathy (DR), in the UKB study.

Results
We identified 49 049 participants with diabetes. Among them, 1023 had type 1 diabetes (T1D), and 40 193 had type 2 diabetes (T2D). A total of 23 833 diabetes subjects had linked primary care records. There were 3237, 3113, and 4922 patients with CVD, DKD, and DR events, respectively. The risk prediction performance for each outcome was assessed, and our results are consistent with the prediction area under the ROC (receiver operating characteristic) curve (AUC) of standard risk prediction models using cohort studies.

Discussion and Conclusion
Our publicly available pipeline and platform enable streamlined curation of incidence events, identification of time-varying risk factors underlying disease progression, and the definition of a relevant cohort for time-to-event analyses. These important steps need to be considered simultaneously to study disease progression.
Inhibitory machinery for the functional dystroglycan glycosylation
Authors: Kondo Yuji , Okajima Tetsuya 
Published: February 2023

Abstract
Dystroglycan (DG), a muscular transmembrane protein, plays a critical role in transducing extracellular matrix-derived signals to the cytoskeleton and provides physical strength to skeletal muscle cell membranes. The extracellular domain of DG, α-DG, displays unique glycosylation patterns. Fully functional glycosylation is required for this domain to interact with components of extracellular matrices, including laminin. One of the unique sugar compositions found in such functional glycans on DG is two ribitol phosphates that are transferred by the sequential actions of fukutin (FKTN) and fukutin-related protein (FKRP), which use CDP-ribitol as a donor substrate. These are then further primed for matriglycan biosynthesis. A recent in vitro study reported that glycerol phosphate could be similarly added to α-DG by FKTN and FKRP if they used CDP-glycerol (CDP-Gro) as a donor substrate. However, the physiological relevance of these findings remains elusive. Imae et al. addressed the knowledge gap regarding whether CDP-Gro is present in mammals and how CDP-Gro is synthesized and functions in mammals.
Thermodynamic stability of human lipocalin-type prostaglandin D synthase under various pH conditions
Authors: Iida Tsukimi , Nakatsuji Masatoshi , Teraoka Yoshiaki , Goto Yuji , Yamamura Takaki , Inui Takashi 
Published: February 2023

Abstract
Lipocalin-type prostaglandin D synthase (L-PGDS) binds various hydrophobic small molecules. Since we aim to use human L-PGDS as a carrier in a drug delivery system (DDS) for poorly water-soluble drugs, quality control of the protein is indispensable. In this study, we investigated the thermodynamic stability of human L-PGDS under various pH conditions. Differential scanning calorimetry revealed that the thermal unfolding of L-PGDS was an almost-reversible two-state transition between the native and unfolded states over the pH range from 2.5 to 7.4. The linear relationship of ΔH(Tm) to Tm in this pH range gave a heat capacity change (ΔCp) of 4.76 kJ/(K·mol), which was small compared to those commonly found in globular proteins. The temperature-dependent free energy of unfolding, ΔG(T), specified by Tm, ΔH(Tm) and ΔCp, showed a pH dependence with the highest value at pH 7.4 closest to the isoelectric point of 8.3. The small value of Cp resulted in a large value of ΔG(T), which contributed to the stability of the protein. Taken together, these results demonstrated that human L-PGDS is sufficiently thermostable for storage and practical use and can be useful as a delivery vehicle of protein-based DDS.
Testing for Alpha in Linear Factor Pricing Models with a Large Number of Securities
Authors: Pesaran M Hashem , Yamagata Takashi 
Published: February 2023

Abstract
This article considers tests of alpha in linear factor pricing models when the number of securities, N, is much larger than the time dimension, T, of the individual return series. We focus on class of tests that are based on Student’s t-tests of individual securities which have a number of advantages over the existing standardized Wald type tests, and propose a test procedure that allows for non-Gaussianity and general forms of weakly cross-correlated errors. It does not require estimation of an invertible error covariance matrix, it is much faster to implement, and is valid even if N is much larger than T. We also show that the proposed test can account for some limited degree of pricing errors allowed under Ross’s arbitrage pricing theory condition. Monte Carlo evidence shows that the proposed test performs remarkably well even when T = 60 and N = 5000. The test is applied to monthly returns on securities in the S&P 500 at the end of each month in real time, using rolling windows of size 60. Statistically significant evidence against Sharpe–Lintner capital asset pricing model and Fama–French three and five factor models are found mainly during the period of Great Recession (2007M12–2009M06).
Preexisting evidence and outcome of phase III trials in gastrointestinal oncology: a systematic review
Authors: Bregni Giacomo , Trevisi Elena , Saúde Conde Rita , Vanhooren Michele , Akin Telli Tugba , Assaf Irene , Hendlisz Alain , Di Maio Massimo , Sclafani Francesco 
Published: February 2023

Abstract

Background
A minority of phase III trials in gastrointestinal oncology are positive. We assessed the association between their outcome and the level and characteristics of preexisting evidence.

Methods
EMBASE, PubMed, and proceedings from international meetings were searched for phase III gastrointestinal cancer trials (gastroesophageal, hepatocellular, biliary tract, pancreatic, small bowel, colorectal, anal, stromal, and neuroendocrine) between January 2000 and June 2020. Trials investigating anticancer drugs for advanced disease, with superiority design and standard treatments as control were eligible. The highest level of preexisting evidence was retrieved from the main study report.

Results
A total of 193 phase III trials were included, and 69 (35.8%) met their primary endpoint. Positivity rates were as follows: gastroesophageal 37%, colorectal 48%, pancreatic 17.1%, hepatocellular 20%, neuroendocrine 75%, and both biliary tract and GIST 60%. No information about preexisting evidence was found for 44 trials (22.8%). For the remaining 149, preexisting evidence consisted of phase II studies in 123 cases (82.6%) and phase I studies in 26 cases (17.4%). The probability of success was 34.1%, 35.8%, and 35.7%, respectively (P = .934). No parameter from prior studies predicted the outcome of phase III trials except β &lt; .2 (P = .048). A numerically increased success rate was observed for phase III trials preceded by positive phase II studies (41.9% vs 18.5%, P = .2).

Conclusions
There does not appear to be an association between level of prior evidence and success of phase III gastrointestinal cancer trials. These data, along with the high phase III failure rate, highlight the need to improve the drug development process in this setting.
Does it pay to park in front of a fire hydrant?
Authors: Andrade Chris , Auerbach Jonathan , Bacelar Icaro , Lee Hane , Tan Angela , Vazquez Mariana , Ward Owen 
Published: February 2023

Abstract
You’re a New York motorist, running horribly late, and there’s an empty space beckoning right outside your destination. Problem is, it’s in front of a fire hydrant. Should you risk getting a ticket? Take some advice from Chris Andrade, Jonathan Auerbach, Icaro Bacelar, Hane Lee, Angela Tan, Mariana Vazquez, and Owen Ward