bluuebunny/crossref_metadata_2025_split huggingface dataset:
Increasing severity of early‐onset atopic dermatitis, but not late‐onset, associates with development of aeroallergen sensitization and allergic rhinitis in childhood
Authors: Schoos Ann‐Marie Malby , Chawes Bo Lund , Bønnelykke Klaus , Stokholm Jakob , Rasmussen Morten Arendt , Bisgaard Hans 
Published: September 2021

AbstractBackgroundEarly exposure to allergens through a defect skin barrier has been proposed as a mechanism for inducing sensitization and development of allergic diseases. We hypothesized that early‐onset, severe atopic dermatitis (AD) is associated with development of aeroallergen sensitization and allergic rhinitis.MethodsWe included 368 children from the Copenhagen Prospective Studies on Asthma in Childhood2000 (COPSAC2000) at‐risk mother‐child cohort. AD was diagnosed prospectively based on Hanifin&Rajka's criteria and severity assessed using the Scoring Atopic Dermatitis (SCORAD) index. Early‐onset AD was defined as debut ≤1 year, late‐onset as debut from 1–6 years. Aeroallergen sensitization and allergic rhinitis were diagnosed at ages 6–7 and 12 years. Associations between early‐onset and late‐onset AD and allergy endpoints were calculated using general estimating equations (GEE) models to compute the overall odds ratios (OR) for both time points.ResultsEarly‐onset AD (yes/no) and severity (SCORAD) were associated with development of aeroallergen sensitization during childhood; GEE OR = 1.68 [1.08; 2.62], p = .02 and 1.08 [1.03; 1.12], p < .001, whereas late‐onset AD showed a borderline significant association and late‐onset severity showed no association; GEE OR = 1.65 [0.92; 2.94], p = .08 and 1.01 [0.97; 1.06], p = .55. The same trend was seen for allergic rhinitis with significant association between early‐onset AD and allergic rhinitis; GEE OR = 1.56 [1.01; 2.41], p = .04 and severity; GEE OR = 1.09 [1.05; 1.13], p < .001, whereas late‐onset AD showed no association. The effects on sensitization and rhinitis of early‐onset versus late‐onset AD severity were significantly different: p‐interactionsensitization = .03 and p‐interactionrhinitis < .01.ConclusionIncreasing severity of early‐onset AD, but not late‐onset AD, associates with aeroallergen sensitization and allergic rhinitis later in childhood.
Characterization of pottery from the Neolithic Huadizui site, Henan province, China by using a multi‐analytical approach
Authors: Yuan Chao , Wang Fen , Yuan Shiling 
Published: September 2021

AbstractThis paper represents the first study on the Xinzhai Culture pottery from Huadizui site, China using X‐ray diffraction (XRD), X‐ray fluorescence spectrometry (XRF), and petrographic. Huadizui pottery is considered to be produced locally, and the raw materials for making pottery come from the Xiaoqinling‐Xiong'er Mountain and Songshan Mountain chain. There are at least two or three clay sources or workshops in the Huadizui site, which is evidenced by petrographic characteristics and the chemical composition of samples. All of the investigated samples were mainly related to quartz and feldspar pellets. The corresponding relationship between the characteristics of the matrix and pottery categories reflects potters pursuing the function of vessels at that time. The range of firing temperature of almost all vessels is between 750 and 950°C.
The impact of family physicians in rural maternity care
Authors: Deutchman Mark , Macaluso Francesca , Bray Emily , Evans David , Boulger James , Quinn Kathleen , Pierce Carrie , Onello Emily , Porter Jana , Warren Wendy , Erickson Jay S. , Bright Patrick , Maness Philip , Luke Shanon , James Katherine A. 
Published: September 2021

AbstractBackgroundReduced access to maternity care in rural areas of the United States presents a significant burden to pregnant persons and infants. The objective of this study was to estimate the impact of family physicians (FPs) on access to maternity care in rural United States hospitals, especially where other providers may not be available.MethodsWe administered a survey to 216 rural hospitals in 10 US states inquiring about the number of babies delivered from 2013 to 2017, the types of delivering physicians, and the maternity services offered. We calculated the percentage of rural hospitals in our sample where FPs performed vaginal deliveries, cesareans, and vaginal births after cesarean (VBACs), and the percentage of all babies delivered by FPs. We estimated the distance patients would have to travel for care if FPs were not providing care locally.ResultsThe final study population consisted of 185 rural hospitals. FPs delivered babies in 67% of these hospitals and were the only physicians who delivered babies in 27% of these hospitals. FPs provided VBAC at 18% and cesarean birth services at 46% of the rural hospitals, but with wide geographic differences. Many patients would have to drive an average of 86 miles round‐trip to access care if those FPs were to stop delivering.ConclusionsFamily physicians are essential providers of maternity care in the rural United States. Family Medicine residency programs should ensure that trainees who intend to practice in rural locations have adequate maternity care training to maintain and expand access to maternity care for rural patients and their families.
First‐in‐human study of milvexian, an oral, direct, small molecule factor XIa inhibitor
Authors: Perera Vidya , Wang Zhaoqing , Luettgen Joseph , Li Danshi , DeSouza Mary , Cerra Michael , Seiffert Dietmar 
Published: September 2021

AbstractMilvexian (BMS‐986177/JNJ‐70033093) is a small molecule, active‐site inhibitor of factor XIa (FXIa) being developed to prevent and treat thrombotic events. The safety, tolerability, pharmacokinetics (PKs), and pharmacodynamics (PDs) of milvexian were assessed in a two‐part, double‐blind, placebo‐controlled, sequential single ascending dose (SAD) and multiple ascending dose (MAD) study in healthy adults. Participants in SAD panels (6 panels of 8 participants; n = 48) were randomized (3:1) to receive milvexian (4, 20, 60, 200, 300, or 500 mg) or placebo. The 200‐ and 500‐mg panels investigated the pharmacokinetic impact of a high‐fat meal. Participants in MAD panels (7 panels of 8 participants; n = 56) were randomized (3:1) to receive milvexian (once‐ or twice‐daily) or placebo for 14 days. All milvexian dosing regimens were safe and well‐tolerated, with only mild treatment‐emergent adverse events and no clinically significant bleeding events. In SAD panels, maximum milvexian plasma concentration occurred 3 h postdose in all fasted panels. The terminal half‐life (T1/2) ranged from 8.3 to 13.8 h. In fasted panels from 20 to 200 mg, absorption was dose‐proportional; results at higher doses (300 and 500 mg) were consistent with saturable absorption. Food increased milvexian bioavailability in a dose‐dependent fashion. In MAD panels, steady‐state milvexian plasma concentration was reached within 3 and 6 dosing days with once‐ and twice‐daily dosing, respectively. Renal excretion was less than 20% in all panels. Prolongation of activated partial thromboplastin time was observed and was directly related to drug exposure. These results suggest that the safety, tolerability, PK, and PD properties of milvexian are suitable for further clinical development.
Cardiovascular risk factors early in the course of treatment in people with type 2 diabetes without established cardiovascular disease: A population‐based observational retrospective cohort study
Authors: Khunti Kamlesh , Hertz Christin L. , Husemoen Lise Lotte N. , Mocevic Emina , Nordsborg Rikke B. , Piltoft Johanne S. , Bain Stephen C. 
Published: September 2021

AbstractAimsTo characterise the cardiovascular risk of people with type 2 diabetes without established cardiovascular disease but with risk factors, relative to those with established cardiovascular disease, to provide information on which patients could benefit from early use of glucose‐lowering therapies that also reduce cardiovascular risk.MethodsData from people with type 2 diabetes initiating second‐line glucose‐lowering medication were retrieved from the UK Clinical Practice Research Datalink GOLD database and linked with Hospital Episode Statistics and Office for National Statistics (2001–2016). Cox proportional hazards models were used to estimate relative risks of major adverse cardiovascular events within groups defined by the presence of selected risk factors in people without versus with established cardiovascular disease.ResultsOf 53,182 individuals, 19.4% had established cardiovascular disease (i.e. a prior cardiovascular event). Over 5–7 years’ follow‐up, the rate of major adverse cardiovascular events was 14.0 and 49.6 events/1000 person‐years without and with established cardiovascular disease, respectively (hazard ratio [HR] 0.28, 95% confidence interval [CI] 0.26, 0.29). Compared with a reference HR 1.0 for participants with established cardiovascular disease, estimated glomerular filtration rate <60 mL/min was the single factor associated with the highest risk of major adverse cardiovascular events (HR 0.75, 95% CI 0.70, 0.81) and mortality (HR 1.12, 95% CI 1.07, 1.18) in people with type 2 diabetes without established cardiovascular disease. The combination of chronic kidney disease with older age, smoking and/or dyslipidaemia was associated with a similarly high risk of cardiovascular events in people with type 2 diabetes and without cardiovascular disease compared with those having established cardiovascular disease.ConclusionsThese analyses provide important information to identify people who may benefit from primary prevention of cardiovascular disease. Modifiable cardiovascular risk factors should be controlled early in all individuals with type 2 diabetes (as well as in all individuals with cardiovascular disease).
A real‐world study of alemtuzumab in a cohort of Italian patients
Authors: Russo Cinzia Valeria , Saccà Francesco , Frau Jessica , Annovazzi Pietro , Signoriello Elisabetta , Bonavita Simona , Grasso Roberta , Clerico Marinella , Cordioli Cinzia , Laroni Alice , Capobianco Marco , Torri Clerici Valentina , Sartori Arianna , Cavalla Paola , Maniscalco Giorgia Teresa , La Gioia Sara , Caleri Francesca , Giugno Alessia , Iodice Rosa , Carotenuto Antonio , Cocco Eleonora , Fenu Giuseppe , Zaffaroni Mauro , Baroncini Damiano , Lus Giacomo , Gallo Antonio , De Mercanti Stefania Federica , Lapucci Caterina , Di Francescantonio Valeria , Brambilla Laura , Sormani Maria Pia , Signori Alessio 
Published: September 2021

AbstractBackground and purposeReal‐world data on alemtuzumab are limited and do not provide evidence of its effectiveness after various disease‐modifying therapies (DMTs). Our aim was to provide real‐world data on the impact of clinical variables and previous DMTs on clinical response to alemtuzumab.MethodsSixteen Italian multiple sclerosis centers retrospectively included patients who started alemtuzumab from January 2015 to December 2018, and recorded demographics, previous therapies, washout duration, relapses, Expanded Disability Status Scale (EDSS) score, and magnetic resonance imaging data. Negative binomial regression models were used to assess the effect of factors on annualized relapse (ARR) after alemtuzumab initiation.ResultsWe studied 322 patients (mean age 36.8 years, median EDSS score 3, median follow‐up 1.94 years). Previous treatments were: fingolimod (106), natalizumab (80), first‐line oral agents (56), first‐line injectables (interferon/glatiramer acetate; 30), and other drugs (15). Thirty‐five patients were treatment‐naïve. The pre‐alemtuzumab ARR was 0.99 and decreased to 0.13 during alemtuzumab treatment (p < 0.001). The number of previous‐year relapses was associated with alemtuzumab ARR (adjusted risk ratio [RR] 1.38, p = 0.009). Progression‐free survival was 94.5% after 1 year, and 89.2% after 2 years of alemtuzumab treatment. EDSS score improvement occurred in 13.5% after 1 year, and 20.6% after 2 years. Re‐baselining patients after 6 months of alemtuzumab treatment, led to no evidence of disease activity status in 71.6% after 1 year and 58.9% after 2 years.ConclusionsAlemtuzumab decreases ARR independent of previous therapy, including patients with disease activity during natalizumab treatment. Overall, 90% of patients showed no disease progression, and 20% an improvement after 2 years of alemtuzumab.
Atmospheric brightening counteracts warming‐induced delays in autumn phenology of temperate trees in Europe
Authors: Wu Zhaofei , Chen Shouzhi , De Boeck Hans J. , Stenseth Nils Christian , Tang Jing , Vitasse Yann , Wang Shuxin , Zohner Constantin , Fu Yongshuo H. 
Published: September 2021

AbstractAimOngoing climate warming has been widely reported to delay autumn phenology, which in turn impacts carbon, water, energy and nutrient balances at regional and global scales. However, the underlying mechanisms of autumn phenology responses to climate change have not been fully elucidated. The aims of this study were to determine whether brightening that was defined as the increase of surface solar radiation and warming during recent decades affect autumn phenology in opposite directions and explore the underlying mechanisms.LocationCentral Europe.Time period1950–2016.Major taxa studiedFour dominant European tree species in central Europe: Aesculus hippocastanum, Betula pendula, Fagus sylvatica and Quercus robur.MethodsWe investigated the temporal trends of leaf senescence, preseason temperature and radiation by separating the period of 1950–2016 into two sub‐periods (1950–1982 and 1983–2016) and determined the relationship between temperature, radiation and leaf senescence using partial correlation analysis.ResultsWe found a significant warming and brightening trend after the 1980s in central Europe, yet this led to only slight delays in leaf senescence that cannot be explained by the well‐known positive correlation between leaf senescence and autumn warming. Interestingly, we found opposite effects between warming (partial correlation coefficient, r = .37) and brightening (r = −.23) on leaf senescence. In addition, the temperature sensitivity of leaf senescence decreased with increasing radiation (−5.08 days/℃/108 J/m2).Main conclusionsThe results suggested that brightening accelerated the leaf senescence dates, counteracting the warming‐induced delays in leaf senescence, which may be attributed to photooxidative stress and/or sink limitation. This emphasizes the need to consider radiation to improve the performance of autumn phenology models.
Age and paleoclimatic implication of middle to upper Miocene plant‐bearing strata in the southern Kanazawa area, Ishikawa Prefecture, Central Japan, based on refined Neogene palynostratigraphy in the Hokuriku district
Authors: Teduka Shota , Yamada Toshihiro 
Published: September 2021

Abstract13–8 Ma (middle to late Miocene) is a key period for understanding how the unique vegetation was established in Japan. Palynostratigraphy is useful for estimating the ages of plant‐bearing strata deposited in shallow‐marine and non‐marine environments, but has low temporal resolution for this key period in Japan. We compiled Neogene and early Quaternary palynological records for the Hokuriku district of Central Japan to clarify palynostratigraphic events that may improve the temporal resolution. Our results showed that palynoassemblages changed considerably during 10–6.4 Ma in the Hokuriku district, following a relatively stable period during 13–10 Ma. We found that evergreen Quercus abundance increased at 11.5–10 Ma. We used these palynostratigraphic signatures, along with other biostratigraphic markers, to infer the ages of the Miocene plant‐bearing Saikawa and Koderayama Formations in the southern Kanazawa area of Ishikawa Prefecture in the Hokuriku district. The ages of the Saikawa and Koderayama Formations were inferred as ~13 and 10–6.4 Ma, respectively. The palynoflora of the Koderayama Formation shows floristic similarity to that of present south China, implying that the unique flora of Japan established after the age of the Koderayama Formation.
Rethinking trade union density: A new index for measuring union strength
Authors: Metten Anne 
Published: September 2021

AbstractAlthough trade union density is the most influential and most commonly used indicator to map trade union strength, comparing between countries and time, the author argues that trade union density is lacking both specificity and comparability. Additionally, many studies on industrial relations neglect developing countries. Therefore, the paper offers a new concept based on a combination of different theoretical approaches that identify determinants of trade union strength involving developing countries. On that basis, the author creates a novel, composite index that is better at capturing trade union strength than previous indices. First evaluations of this collective labour force index, which covers the years 2000 to 2016 in 72 countries, show that it is quite capable of doing so.
Antimicrobial protein REG3A and signaling networks are predictive of stroke outcomes
Authors: Sands Madison , Frank Jacqueline A. , Maglinger Benton , McLouth Christopher J. , Trout Amanda L. , Turchan‐Cholewo Jadwiga , Stowe Ann M. , Fraser Justin F. , Pennypacker Keith R. 
Published: September 2021

AbstractRegenerating Family Member 3 Alpha (REG3A) is a multifunctional protein with antimicrobial activity, and primarily secreted by the intestine and pancreas. Studies have shown an increased expression of REG3A in systemic inflammatory responses to acute injury and infection, but studies investigating REG3A during the pathogenesis of ischemic stroke are limited. The aims of this study were to examine the associations between arterial expression of REG3A and other arterial inflammatory proteins implicated in stroke pathogenesis, as well as associations between REG3A and markers of poor outcome for ischemic stroke. The University of Kentucky Blood and Clot Thrombectomy Registry and Collaboration (BACTRAC) protocol (clinicaltrials.gov NCT03153683) utilizes thrombectomy to isolate intracranial arterial blood (i.e. distal to thrombus) and systemic arterial blood (i.e. carotid). Samples were analyzed by Olink Proteomics for N = 42 subjects. Statistical analyses of plasma proteins included 2‐sample t‐tests, spearman and biserial correlations, and robust regression models to elucidate network signaling and association to clinical outcomes. Results indicated that levels of systemic REG3A were positively correlated with inflammatory proteins interleukin IL6 (R = 0.344, p = 0.030) and IL17C (R = 0.468, p = 0.002). 2‐sided t‐ tests examining differences of systemic REG3A within quartiles of NIHSS admission score depicted significant differences between quartiles. Those with NIHSS scores corresponding to moderate and moderate‐severe neurofunctional deficits had significantly higher levels of systemic REG3A compared to those with NIHSS scores corresponding to mild and mild‐moderate neurofunctional deficits (p = 0.016). STRING analyses of proteins in each robust regression model demonstrated substantial networking between REG3A and other systemic proteins highly relevant to ischemic stroke. The present study provides novel data on systemic REG3A in the context of ischemic stroke. These results demonstrate the influential role of REG3A regarding surrogate functional and radiographic outcomes of stroke severity. Additionally, they provide novel insight into the role of REG3A and related proteins during the complex neuroinflammatory process of ischemic stroke. These data provide a foundation for future studies to investigate REG3A and related networking proteins as potential biomarkers with prognostic potential, as well as potential therapeutic targets.
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Expression profiles of tRNA‐derived small RNA and their potential roles in oral submucous fibrosis
Authors: Zeng Liujun , Peng Hui , Yu Huiqiao , Wang Weiming , Duan Chaojun , Fang Changyun , Wu Yingfang 
Published: September 2021

AbstractBackgroundAlthough transfer RNA (tRNA) has been found to be the main source of a rich class of noncoding RNA, the tRNA‐derived small RNA (tsRNA) has been proved to play an irreplaceable role in the human body, and its dynamic imbalance could affect the progress of the disease. However, the research on tsRNA in oral submucous fibrosis (OSF) is still scarce.MethodsWe sequenced the OSF and validated it by PCR. We found that there were significant differences in their expression levels in OSF. Furthermore, bioinformatic analysis was performed to explore the roles of these fragments in oral submucous fibrosis.ResultsOf 126 tsRNAs in OSF were dysregulated, including 73 upregulated tsRNAs and 53 downregulated tsRNAs. The downregulated tiRNA‐Val‐CAC‐002, tRF‐Asn‐GTT‐005, tRF‐Trp‐CCA‐007 and upregulated tRF‐Gly‐TCC‐016, tRF‐Pro‐TGG‐009 showed significant differences by qRT‐PCR validation, which were consistent with the results of RNA sequencing. Gene ontology and pathway analysis revealed that tRF‐Gly‐TCC‐016 would possibly promote the formation and progress of OSF through cytokine‐cytokine receptor interaction and cAMP signal pathway, while tiRNA‐Val‐CAC‐002 could be primarily concerned with the transition from OSF to oral squamous cell carcinoma (OSCC).ConclusiontRNA‐derived fragments are dysregulated and could be involved in the pathogenesis of oral submucous fibrosis. tRF‐Gly‐TCC‐016 and tiRNA‐Val‐CAC‐002 may be new regulatory molecules that could affect the process of OSF by regulating signal pathways through interacting with multiple genes.
Pharmacokinetics of butorphanol in male neutered cats anesthetized with isoflurane
Authors: Pypendop Bruno H. , Shilo‐Benjamini Yael 
Published: September 2021

AbstractThis study characterized the pharmacokinetics of butorphanol in cats anesthetized with isoflurane. Six young healthy male neutered cats were used. Cats were anesthetized with isoflurane in oxygen. Catheters were placed in a jugular vein for blood sampling and in a medial saphenous vein for butorphanol and lactated Ringer's solution administration. Butorphanol tartrate (1 mg/kg over 5 min) was administered intravenously. Blood samples were collected prior to butorphanol administration and at various times up to 365 min following administration. Plasma butorphanol concentration was measured using liquid chromatography/tandem mass spectrometry. Compartment models were fitted to the time‐concentration data using nonlinear mixed effect modeling. A three‐compartment model best fitted the data. Typical value (% interindividual variability) for the three volumes of distribution, the metabolic clearance, and the two distribution clearances were 230 (72), 1095 (not estimated), and 2596 (not estimated) ml/kg, and 18.4 (72), 169.6 (52), and 55.0 (43), respectively. Pharmacokinetic simulation suggested that a loading dose (µg/kg) calculated as 0.287 × target plasma concentration in ng/ml (CT) followed by intravenous infusions (µg/kg/min) of 0.098 × CT for 20 min, 0.049 × CT for 40 min, and 0.022 × CT thereafter would rapidly achieve and maintain CT ± 10% for up to 6.5 h.