bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pharmacogenetics of trough serum anti‐TNF levels in paediatric inflammatory bowel disease
Authors: Salvador‐Martín Sara , Pujol‐Muncunill Gemma , Bossacoma Ferran , Navas‐López Víctor Manuel , Gallego‐Fernández Carmen , Segarra Oscar , Clemente Susana , Muñoz‐Codoceo Rosana , Viada Javier , Magallares Lorena , Martínez‐Ojinaga Eva , Moreno‐Álvarez Ana , Solar‐Boga Alfonso , Loverdos Inés , Merino‐Bohórquez Vicente , Balboa‐Vega María Jesús , Rodriguez‐Martinez Alejandro , Alvarez‐Vayo Concepción , Sanchez Cesar , Tolin Mar , Blanca‐García José Antonio , García‐Romero Ruth , Eizaguirre Francisco Javier , Sánchez‐Hernandez José Germán , de Caldas Rafael Gonzalez , Millán‐Jimenez Antonio , Aznal Elena , Abarca‐Zabalía Judith , Sanjurjo‐Sáez María , López‐Fernández Luis Andrés 
Published: June 2020

AimsIdentifying DNA variants associated with trough serum anti‐tumour necrosis factor (TNF) levels could predict response to treatment in inflammatory bowel disease (IBD). To date, no specific studies have been performed in children. The aim of this study was to identify genetic variants associated with trough serum anti‐TNF levels and whether these variants are differential markers for infliximab and adalimumab.MethodsWe included 154 children (age < 18 years) from 17 hospitals who had been diagnosed with IBD and actively treated with infliximab or adalimumab. Twenty‐one polymorphisms were genotyped using real‐time PCR. Trough serum anti‐TNF levels were measured using enzyme‐linked immunosorbent assay (ELISA). The association between DNA polymorphisms and the therapeutic range or the absolute values of anti‐TNF drugs was analysed by Fisher exact test, student's t‐test and logistic regression.ResultsThe variants rs5030728 (TLR4) and rs11465996 (LY96) were associated with subtherapeutic infliximab levels. rs1816702 (TLR2) was associated with supratherapeutic levels and rs3397 (TNFRSF1B) with subtherapeutic levels of adalimumab (P < .05). In addition, rs1816702 (TLR2) and rs2569190 (CD14) were associated with absolute values of trough serum adalimumab, and rs2569190 (CD14) was associated with absolute values of trough serum adalimumab and infliximab (P < .05).ConclusionGenotyping of these DNA variants before starting treatment may help to select the best anti‐TNF drug in paediatric patients. The SNP rs1816702 is the most promising marker for tailoring the anti‐TNF regimen in children with IBD. For the first time, DNA variants are associated with trough serum anti‐TNF levels.
Environmental conditions at the Last Interglacial (Eemian) site Neumark‐Nord 2, Germany inferred from stable isotope analysis of freshwater mollusc opercula
Authors: Milano Stefania , Pop Eduard , Kuijper Wim , Roebroeks Wil , Gaudzinski‐Windheuser Sabine , Penkman Kirsty , Kindler Lutz , Britton Kate 
Published: June 2020

Mollusc biogenic carbonates are valuable records of past environmental conditions. In particular, carbonate oxygen (δ18O) and carbon (δ13C) stable isotopes can be used to reconstruct different physical and chemical parameters, according to the different genera used (marine, freshwater or terrestrial). The Last Interglacial (early Eemian) palaeolake of Neumark‐Nord 2 (NN2), Germany provides an excellent example of a Neanderthal archaeological site with abundant freshwater carbonate remains. As in other European contexts, one of the most abundant species is Bithynia tentaculata. In order to provide a robust regional baseline for the interpretation of the archaeological data, this study includes a calibration phase on modern B. tentaculata opercula. The results indicate that these calcitic structures are likely to be subjected to a growth slowdown/cessation during summer, which influences their geochemistry, reflecting mainly the water properties of the rest of the year. This modern calibration, together with the existing palaeoenvironmental reconstructions developed for NN2 (e.g. pollen data), represents a valuable opportunity to establish B. tentaculata opercula as reliable environmental proxies applicable to several other freshwater contexts. The isotope data of the NN2 opercula, in agreement with the pollen record, indicate that the major archaeological horizon was formed during a rather wet period and potentially in a semi‐forested environment. However, human occupation occurred also during drier phases at the site and within a wide temperature range, indicating the absence of restricted environmental preferences by the local Neanderthal groups.
Morphometry of lower cheek teeth of cave bears (Carnivora, Ursidae) and general remarks on the dentition variability
Authors: Baryshnikov Gennady F. , Puzachenko Andrey Y. 
Published: June 2020

The variability of lower 6776 cheek teeth of spelaeoid (Ursus spelaeus,U. kanivetz,U. deningeri,U. kudarensis,U. saviniandU. rossicus) and arctoid lineages (extant and extinctU. arctos) recovered from 176 palaeontological localities was analysed by methods of univariate and multivariate statistics. For comparison, teeth ofU. minimusandU. etruscusspecies, which are ancestral taxa for cave bears and brown bear, were studied. The performed analyses indicate great variability of tooth crown in lower cheek teeth; no distinct general trend was identified in the changes, except for an increase in p4 roundness and in m3 size fromU. minimusto big cave bears. Centroids ofU. minimusandU. etruscusare at a great distance from those of cave bears;U. arctosoccupies an intermediate position between the two groups. Molar characteristics in general are close inU. saviniandU. rossicus. The bear species are differentiated in the morphospaces by morphometric variations in the lower cheek teeth but less markedly than in the morphospaces of the upper cheek teeth. A test of the inhibitory developmental cascade model showed that a linear relationship between lower molar dimensions became clear only after premolar p4 was included in the model. Evolutionary trends were found in the tooth changes with time (differently expressed in individual species and in different teeth) depending on environments, in particular on the elevation of the locality above the sea level. The allometric pattern differentiation does not always coincide with phylogenetic relationships between taxa, being most often revealed at the subspecies level. There is a dominant covariance between the upper and lower rows of teeth in accordance with the occlusion scheme. It may vary in manifestation depending on the particular species.
Utilization of speech‐language, occupational and physical therapy by diagnosis of autism spectrum disorder
Authors: Yingling Marissa E. , Bell Bethany A. 
Published: June 2020

AbstractBackgroundAlthough Medicaid coverage of treatment for children with autism spectrum disorder (ASD) is expanding, we know little about when children receive speech‐language, occupational and/or physical therapy. The objective of this study was to examine the relationships between predisposing, enabling and need characteristics and utilization of speech‐language, occupational and physical therapy by diagnosis of ASD.MethodsWe integrated administrative, Medicaid and Census data using a large sample of children with ASD who enrolled in a 1915(c) Home and Community Based Medicaid waiver in a south‐eastern state (N= 1,968) to explore (1) the percent of treatment utilization by ASD diagnosis, (2) the type of therapy utilized and (3) the predisposing, enabling and need characteristics associated with utilization.ResultsThe percent of utilization was 71%; 65.8% utilized SLT, 33.4% utilized OT and 18.4% utilized PT. Enabling (i.e., urbanicity, age of diagnosis and early intervention programme enrolment) and need (i.e., intellectual disability) characteristics were associated with utilization whereas predisposing social characteristics (i.e., sex and child race‐ethnicity and neighbourhood racial composition, poverty and affluence) were not associated with utilization.ConclusionsFindings highlight the value in monitoring when children begin treatment. As governments in the United States and globally work to maximize children's potential, additional research that can inform efforts to facilitate earlier utilization will be key to promoting optimal outcomes.
Land rental markets and labor productivity: Evidence from rural China
Authors: Zhang Jian , Mishra Ashok K. , Zhu Peixin 
Published: June 2020

AbstractThis study investigates the impact of the land rental market on labor productivity in rural China. Particular attention is given to farm and nonfarm labor productivity. Using 2012 household‐level data and a multinomial endogenous switching treatment regression technique, we find that rural households renting in farmland increased labor productivity in the farm sector by about 55%, whereas labor productivity in the nonfarm sector decreased by about 6%. We also find that rural households renting out farmland had lower labor productivity in both the farm and nonfarm sectors by 13% and 9%, respectively. More family labor transferred from the farm to the nonfarm sector after renting out land.
IT Outsourcing and Vendor Cost Improvement Strategies under Asymmetric Information
Authors: Jain Tarun , Hazra Jishnu , Cheng T.C. Edwin 
Published: June 2020

ABSTRACTIn this article, we study the scenario under which two information technology (IT) vendor firms compete for the outsourcing requirements of a client firm. The vendors' cost structures are private information. In addition, the vendors can improve their unit costs through learning‐by‐doing and by making investments in process improvement, that is, induced learning. We study the impacts of vendor‐based learning and process improvement in the asymmetric cost setting on the client firm's outsourcing strategy and the vendor firms' process improvement investments. Our analysis reveals that the client firm may adopt the single‐sourcing strategy or a combination of dual and single‐sourcing strategies depending on the learning efficiency of the vendor base. We also find that high heterogeneity in the vendor cost structure increases the first‐period outsourcing requirements of the client firm. Our findings provide interesting managerial implications for the IT outsourcing industry.
Role of Analytics for Operational Risk Management in the Era of Big Data
Authors: Araz Ozgur M , Choi Tsan‐Ming , Olson David L , Salman F. Sibel 
Published: June 2020

ABSTRACTOperational risk management (ORM) is critical for any organization, and in the big data era, analytical tools for operational risk management are evolving faster than ever. This paper examines recent developments in academic ORM literature from the data analytics perspective. We focus on identifying present trends in ORM related to various types of natural and man‐made disasters that have been challenging all aspects of life. Although we examine the broader operations management (OM) literature, we keep the focus on the articles published in the well‐regarded OM journals, including both empirical and analytical outlets. We highlight how the use of data analytics tools and methods have facilitated ORM. We discuss the need for data monitoring and the integration of various analytical tools into decision making processes by classifying the literature on application fields, analytics techniques, and the strategies used for implementation. We summarize our findings and propose a process to implement data‐driven ORM with future research directions.
Glucagon‐like peptide‐1 receptor agonists and sodium‐glucose co‐transporter‐2 inhibitors as combination therapy for type 2 diabetes: A systematic review and meta‐analysis
Authors: Mantsiou Chrysanthi , Karagiannis Thomas , Kakotrichi Panagiota , Malandris Konstantinos , Avgerinos Ioannis , Liakos Aris , Tsapas Apostolos , Bekiari Eleni 
Published: June 2020

AbstractAimTo assess the efficacy and safety of combination therapy with a glucagon‐like peptide‐1 receptor agonist (GLP‐1 RA) and a sodium‐glucose co‐transporter‐2 inhibitor (SGLT2i) in patients with type 2 diabetes.MethodsWe searched Medline, Embase, the Cochrane Library and grey literature sources up to 2 December 2019 for randomized controlled trials in adults with type 2 diabetes assessing the combination of GLP‐1RA and SGLT2i, either as co‐initiation therapy or as add‐on to each other, against placebo or an active comparator. The primary outcome was change in HbA1c. Secondary outcomes included change in body weight, blood pressure and estimated glomerular filtration rate, and incidence of severe hypoglycaemia, all‐cause mortality, cardiovascular mortality, myocardial infarction, stroke and hospitalization for heart failure. We pooled data using random effects meta‐analyses.ResultsSeven trials (1913 patients) were eligible. Compared with GLP‐1RA, GLP‐1RA/SGLT2i combination therapy was associated with a greater reduction in HbA1c (weighted mean difference −0.61%, 95% CI −1.09% to −0.14%, four studies), body weight (−2.59 kg, −3.68 to −1.51 kg, three studies) and systolic blood pressure (−4.13 mmHg, −7.28 to −0.99 mmHg, four studies). Compared with SGLT2i, GLP‐1RA/SGLT2i combination therapy reduced HbA1c (−0.85%, −1.19% to −0.52%, six studies) and systolic blood pressure (−2.66 mmHg, −5.26 to −0.06 mmHg, six studies), but not body weight (−1.46 kg, −2.94 to 0.03 kg, five studies). After excluding data for one trial that had a considerably longer duration than the remaining studies, body weight was also reduced versus SGLT2i (−1.79 kg, −2.99 to −0.59 kg, five studies). Combination therapy did not increase the incidence of severe hypoglycaemia. Data for mortality and cardiovascular outcomes were scarce.ConclusionsGLP‐1RA/SGLT2i combination therapy seems to reduce HbA1c, body weight and systolic blood pressure without increasing the risk of severe hypoglycaemia compared with either GLP‐1RA or SGLT2i. No conclusions can be made regarding long‐term effectiveness or the effect on cardiovascular outcomes.
The impact of tocilizumab on anxiety and depression in patients with rheumatoid arthritis
Authors: Tiosano Shmuel , Yavne Yarden , Watad Abdulla , Langevitz Pnina , Lidar Merav , Feld Joy , Tishler Moshe , Aamar Suhail , Elkayam Ori , Balbir‐Gurman Alexandra , Molad Yair , Ehrlich Sharon , Abu‐Shakra Mahmoud , Amital Daniela , Amital Howard 
Published: June 2020

AbstractBackgroundMood disorders, such as anxiety and depression, are extremely prevalent among patients with rheumatoid arthritis (RA). In this study, we assessed the impact of treatment with tocilizumab (TCZ), an IL‐6 antagonist, upon anxiety and depressive symptoms in a cohort of RA patients.Materials and MethodsStudy participants were adults diagnosed with RA who received a weekly subcutaneous injection of tocilizumab for 24 weeks. We used the Hamilton Depression (HDRS) and Anxiety (HAMA) scores in order to assess the severity of depression and anxiety, respectively. RA disease activity indices and depression and anxiety levels were assessed at baseline, 4 weeks and study completion.ResultsUltimately, 91 patients were included in the study. The mean age was 54 years, and the majority were female (79%). The mean score in all disease activity indices as well as depression and anxiety levels decreased dramatically from baseline to study completion. Sixty patients (66%) demonstrated a significant decrease in anxiety and/or depression levels. When logistic regression was performed, an HDRS score indicative of depression at study baseline demonstrated an independent association with a significant psychiatric response whilst older age and increased baseline weight were negatively associated. HAMA and HDRA scores correlated with the following RA disease activity parameters, respectively; HAQ‐DI (r = .4, .42), DAS28 (r = .29, .32) and CDAI (0.28 and 0.33), all of them were statistically significant (P < .01).ConclusionsThis study has demonstrated a favourable impact of TCZ therapy on parameters reflecting depression and anxiety severity in patients with RA.
How community adaptation affects biodiversity–ecosystem functioning relationships
Authors: Aubree Flora , David Patrice , Jarne Philippe , Loreau Michel , Mouquet Nicolas , Calcagno Vincent 
Published: June 2020

AbstractEvidence is growing that evolutionary dynamics can impact biodiversity–ecosystem functioning (BEF) relationships. However the nature of such impacts remains poorly understood. Here we use a modelling approach to compare random communities, with no trait evolutionary fine‐tuning, and co‐adapted communities, where traits have co‐evolved, in terms of emerging biodiversity–productivity, biodiversity–stability and biodiversity–invasion relationships. Community adaptation impacted most BEF relationships, sometimes inverting the slope of the relationship compared to random communities. Biodiversity–productivity relationships were generally less positive among co‐adapted communities, with reduced contribution of sampling effects. The effect of community‐adaptation, though modest regarding invasion resistance, was striking regarding invasion tolerance: co‐adapted communities could remain very tolerant to invasions even at high diversity. BEF relationships are thus contingent on the history of ecosystems and their degree of community adaptation. Short‐term experiments and observations following recent changes may not be safely extrapolated into the future, once eco‐evolutionary feedbacks have taken place.
Psychoacoustics and neurophysiological auditory processing in patients with Charcot‐Marie‐Tooth disease types 1A and 2A
Authors: Choi J. E. , Seol H. Y. , Seok J. M. , Hong S. H. , Choi B.‐O. , Moon I. J. 
Published: June 2020

Background and purposeHidden hearing loss has been reported in patients with Charcot‐Marie‐Tooth (CMT) disease; however, the auditory‐processing deficits have not been widely explored. We investigated the psychoacoustic and neurophysiological aspects of auditory processing in patients with CMT disease type 1A (CMT1A) and type 2A (CMT2A).MethodsA total of 43 patients with CMT1A and 15 patients with CMT2A were prospectively enrolled. All patients with CMT disease had normal sound‐detection ability by using pure‐tone audiometry. Spectral‐ripple discrimination, temporal modulation detection and auditory frequency‐following response were compared between CMT1A, CMT2A and control groups.ResultsAlthough all participants had normal audiograms, patients with CMT disease had difficulty understanding speech in noise. The psychoacoustic auditory processing was somewhat different depending on the underlying pathophysiology of CMT disease. Patients with CMT1A had degraded auditory temporal and spectral processing. Patients with CMT2A had no reduced spectral resolution, but they showed further reduced temporal resolution than the patients with CMT1A. The amplitudes of the frequency‐following response were reduced in patients with CMT1A and CMT2A, but the neural timing remained relatively intact.ConclusionsWhen we first assessed the neural representation to speech at the brainstem level, the grand average brainstem responses were reduced in both patients with CMT1A and CMT2A compared with healthy controls. As the psychoacoustic aspects of auditory dysfunctions in CMT1A and CMT2A were somewhat different, it is necessary to consider future auditory rehabilitation methods based on their pathophysiology.
Discovery of lipophilic two‐pore channel agonists
Authors: Gerndt Susanne , Krogsaeter Einar , Patel Sandip , Bracher Franz , Grimm Christian 
Published: June 2020

Two‐pore channels (TPCs) have been a hot topic in recent literature. Their involvement in various diseases such as viral infections and cancer is of great interest for drug research. Due to their localization in the endolysosomal system and the lack of cell‐permeable activators, complex techniques were required for studying channel functions. Here, we review the first published lipophilic small‐molecule activators of TPCs. In independent high‐throughput screens, several new agonists were discovered, which now allow simple and fast investigation of TPCs in more detail in intact cells and in vivo. Zhang et al. identified tricyclic and phenothiazine antidepressants as TPC1 and TPC2 activators by screening a library of approved drugs. In contrast, Gerndt et al. screened an extensive compound library with mostly new chemotypes and drug structures. The latter resulted in two structurally distinct high‐affinity agonists, which are able to selectively activate TPC2 in either an NAADP‐ or PI(3,5)P2‐like manner. Here, we discuss the advantages and drawbacks of the identified molecules and their structural features. The versatility by which TPCs can be activated indicates many opportunities for future studies.
A reply to the ‘critical evaluation of the Oscillayers methods and dataset’
Authors: Gamisch Alexander 
Published: June 2020

AbstractBrown, Hill & Haywood (2020) offered a critical evaluation of the theory and methods of the Oscillayers approach and attempted to test its utility by reproducing global circulation model (GCM)‐based palaeoclimatic reconstructions of two variables (Bio1 and Bio12) for four different time points (130 ka, 787 ka, 3.2 Ma and 3.3 Ma). They concluded that Oscillayers show poor agreement with independent GCMs and thus do not provide a robust approximation of palaeoclimate throughout the Plio‐Pleistocene. Here, I demonstrate that the authors underestimated the ability of Oscillayers to reproduce independent GCMs by not taking into account inter‐framework differences between the models used to generate the Oscillayers and PaleoClim datasets. However, upon correcting this systematic error, differences in Bio1 and Bio12 between Oscillayers and PaleoClim GCMs are less than ± 1°C or ± 50 mm, on average, in 35.9% (range: 11.8–59.0%) or 46.7% (20.8–66.0%) of values, respectively. Thus, the agreement between Oscillayers and PaleoClim is, on average, c. 1.5–2 times higher than estimated by Brown et al. (2020) and mostly well above the inter‐model agreement between two commonly used GCMs (CCSM and MIROC) for the Last Glacial Maximum. Consequently, I conclude that the Oscillayers approach does provide reasonably robust approximations of palaeoclimate throughout the Plio‐Pleistocene. Some clarifications are given.
Proximity and distance: Think tanks handling the independence paradox
Authors: Jezierska Katarzyna , Sörbom Adrienne 
Published: June 2020

AbstractThe credibility of think tanks is grounded in their image as independent experts. In order to gain authority to act, think tanks must be seen as independent, but in order to exert influence and gain funding, think tanks are forced to compromise this independent image. We focus on how think tanks handle this independence paradox. How do think tanks use different resources to construct an independent image? The aim of the article is conceptual, as we develop a theoretical model of the independence paradox. This conceptual work is based on empirical analysis of attempts by think tanks in Poland and Sweden to create independence while maintaining influence. The two desirables central for think tanks, independence and influence, force them to make strategic choices about their relations with various actors. We conclude that the processes of keeping distance and arranging proximity are at the core of the independence paradox.