bluuebunny/crossref_metadata_2025_split huggingface dataset:
A missense variant Arg611Cys inLIPEwhich encodes hormone sensitive lipase decreases lipolysis and increases risk of type 2 diabetes in American Indians
Authors: Muller Yunhua L. , Sutherland Jeff , Nair Anup K. , Koroglu Cigdem , Kobes Sayuko , Knowler William C. , Van Hout Cristopher V. ,   Regeneron Genetics Center, Shuldiner Alan R. , Hanson Robert L. , Bogardus Clifton , Baier Leslie J. 
Published: October 2021

AbstractAimsHormone sensitive lipase (HSL), encoded by theLIPEgene, is involved in lipolysis. Based on prior animal and human studies,LIPEwas analysed as a candidate gene for the development of type 2 diabetes (T2D) in a community‐based sample of American Indians.Materials and methodsWhole‐exome sequence data from 6782 participants with longitudinal clinical measures were used to identify variation inLIPE.ResultsAmongst the 16 missense variants identified, an Arg611Cys variant (rs34052647; Cys‐allele frequency = 0.087) significantly associated with T2D (OR [95% CI] = 1.38 [1.17–1.64],p = 0.0002, adjusted for age, sex, birth year, and the first five genetic principal components) and an earlier onset age of T2D (HR = 1.22 [1.09–1.36],p = 0.0005). This variant was further analysed for quantitative traits related to T2D. Amongst non‐diabetic American Indians, those with the T2D risk Cys‐allele had increased insulin levels during an oral glucose tolerance test (0.07 SD per Cys‐allele,p = 0.04) and a mixed meal test (0.08 log10µU/ml per Cys‐allele,p = 0.003), and had increased lipid oxidation rates post‐absorptively and during insulin infusion (0.07 mg [kg estimated metabolic body size {EMBS}]−1 min−1per Cys‐allele for both,p = 0.01 and 0.009, respectively), compared to individuals with the non‐risk Arg‐allele.In vitrofunctional studies showed that cells expressing the Cys‐allele had a 17.2% decrease in lipolysis under isoproterenol stimulation (p = 0.03) and a 21.3% decrease in lipase enzyme activity measured by usingp‐nitrophenyl butyrate as a substrate (p = 0.04) compared to the Arg‐allele.ConclusionThe Arg611Cys variant causes a modest impairment in lipolysis, thereby affecting glucose homoeostasis and risk of T2D.
Irreproducibility in searches of scientific literature: A comparative analysis
Authors: Pozsgai Gábor , Lövei Gábor L. , Vasseur Liette , Gurr Geoff , Batáry Péter , Korponai János , Littlewood Nick A. , Liu Jian , Móra Arnold , Obrycki John , Reynolds Olivia , Stockan Jenni A. , VanVolkenburg Heather , Zhang Jie , Zhou Wenwu , You Minsheng 
Published: October 2021

Abstract

Repeatability is the cornerstone of science, and it is particularly important for systematic reviews. However, little is known on how researchers’ choice of database, and search platform influence the repeatability of systematic reviews. Here, we aim to unveil how the computer environment and the location where the search was initiated from influence hit results.

We present a comparative analysis of time‐synchronized searches at different institutional locations in the world and evaluate the consistency of hits obtained within each of the search terms using different search platforms.

We revealed a large variation among search platforms and showed that PubMed and Scopus returned consistent results to identical search strings from different locations. Google Scholar and Web of Science's Core Collection varied substantially both in the number of returned hits and in the list of individual articles depending on the search location and computing environment. Inconsistency in Web of Science results has most likely emerged from the different licensing packages at different institutions.

To maintain scientific integrity and consistency, especially in systematic reviews, action is needed from both the scientific community and scientific search platforms to increase search consistency. Researchers are encouraged to report the search location and the databases used for systematic reviews, and database providers should make search algorithms transparent and revise access rules to titles behind paywalls. Additional options for increasing the repeatability and transparency of systematic reviews are storing both search metadata and hit results in open repositories and using Application Programming Interfaces (APIs) to retrieve standardized, machine‐readable search metadata.
LDL‐cholesterol and PCSK9 in patients with familial hypercholesterolemia: influence of PCSK9 variants under lipid‐lowering therapy
Authors: Hamasaki Masato , Sakane Naoki , Hara Kazuo , Kotani Kazuhiko 
Published: October 2021

AbstractBackgroundFamilial hypercholesterolemia (FH), an autosomal dominant genetic disease with the elevated levels of low‐density lipoprotein (LDL) cholesterol (LDL‐C), increases the risk of coronary artery disease (CAD). The proprotein convertase subtilisin/kexin type 9 (PCSK9) gene is associated with FH. There is a positive relationship between circulating LDL‐C and PCSK9 levels, a potential CAD condition, without lipid‐lowering therapy (LLT); however, we do not know whether their correlation exists in FH patients under LLT.MethodsThis study compared the correlation of PCSK9 variants among patients with FH under LLT (n = 70; mean age, 53 years; male, 63%). LDLR, PCSK9 and APOB variants were analyzed using next‐generation sequencing.ResultsThe LDL‐C and PCSK9 levels in patients with gain‐of‐function (GOF) variants of PCSK9 (n = 7) were mostly similar to those in patients with LDLR variants (n = 17) or variant‐negative patients (n = 46). A significant positive correlation was observed between LDL‐C and PCSK9 levels in patients with GOF variants of PCSK9 (r = 0.79, p = 0.04), but not in patients with LDLR variants or variant‐negative patients.ConclusionThe LDL‐C‐PCSK9 correlation is suggested to be retained in FH patients with GOF variants of PCSK9 even under LLT, and these variants can be used as molecular markers for additional treatment with statins in FH patients.
Improved Tricuspid Valve Function, Preload Recruitment and Ventricular Efficiency During Submaximal Exercise in Patients with Unoperated Ebstein's Anomaly: An MRI Study
Authors: Ferrari Irene , Shehu Nerejda , Nagdyman Nicole , Martinoff Stefan , Ewert Peter , Stern Heiko , Meierhofer Christian 
Published: October 2021

BackgroundAdolescents and adults with native Ebstein's anomaly (EA) are at the benign part of the Ebstein spectrum, having survived infancy without surgery. In this population, surgical indication and timing remain objects of controversy and depend, among other factors, on exercise capacity.PurposeTo better understand the pathophysiology of exercise adaptation in native EA.Study TypeRetrospective.PopulationTen patients with unoperated EA (age range 18–61 years) and 13 healthy subjects as controls.Field Strength/SequenceBalanced steady‐state free precession cine and phase contrast flow sequences at 1.5 T.AssessmentWe measured volumes and flows at rest and during submaximal exercise. Hemodynamic parameters including stroke volume (SV), cardiac index (CI), ejection fraction (EF), and tricuspid regurgitation (TR) were calculated.Statistical TestsWe used nonparametric Mann–Whitney U‐test and Wilcoxon signed‐rank test. A P‐value of <0.05 was considered statistically significant.ResultsRest CI and SV were significantly higher in controls; rest heart rate (HR) was similar in the two groups (median 71 bpm by patients and 65 bpm by controls, P = 0.448). During exercise, CI increased significantly in both groups: from 2.40 to 3.35 L/min/m2 in the patient group and from 3.60 to 4.20 L/min/m2 in controls; HR increased significantly in both groups. SV increased significantly in the patient group, whereas it remained stable in controls (P = 0.5284). Patients' median TR decreased significantly: median 42% at rest and 30% during exercise; concomitantly, left ventricular (LV) preload increased significantly (+3% indexed LV end‐diastolic volume) as did LVEF (median 59% at rest vs. 65% during exercise).Data ConclusionDuring submaximal exercise, patients with mild to moderate EA improved their cardiovascular system's total efficiency by increasing CI; this was obtained by an increase in HR and by the recruitment of volume, as shown by an increased LV end‐diastolic volume and SV, with simultaneous decrease in TR. This was different from healthy subjects in which CI increased only due to HR increase.Level of Evidence3Technical Efficacy Stage3
Prenatal diagnosis of combined methylmalonic acidemia and homocystinuria cobalamin C type using clinical exome sequencing and targeted gene analysis
Authors: Hwang Narae , Jang Ja‐Hyun , Cho Eun‐Hae , Choi Rihwa , Choi Suk‐Joo , Park Hyung‐Doo 
Published: October 2021

AbstractBackgroundCombined methylmalonic acidemia and homocystinuria is a rare inherited disorder of intracellular cobalamin metabolism caused by biallelic variants in one of the following genes: MMACHC (cblC), MMADHC (cblD), LMBRD1 (cblF), ABCD4 (cblJ), THAP11 (cblX‐like), and ZNF143 (cblX‐like), or a hemizygous variant in HCFC1 (cblX). Prenatal diagnosis of combined methylmalonic acidemia with homocystinuria is crucial for high‐risk couples since the disorder can be life‐threatening for offspring. We would like to describe two infant deaths both of which are likely attributable to cblC despite not having a genetic confirmation, and subsequent pregnancy and prenatal genetic testing.MethodsParental clinical exome sequencing and targeted Sanger sequencing of MMACHC gene in amniotic fluid was performed to check the carrier status of the fetus.ResultsParental clinical exome sequencing revealed a heterozygous pathogenic variant [NM_015506.2:c.217C>T (p.Arg73*)] in the MMACHC gene of the mother and [NM_015506.2:c.609G>A (p.Trp203*)] in the MMACHC gene of the father. Targeted Sanger sequencing of MMACHC gene in amniotic fluid revealed that the fetus carried only one nonsense variant [NM_015506.2:c.609G>A (p.Trp203*)], which was inherited from the father. The mother delivered a healthy baby and the neonate did not show any symptoms or signs of combined methylmalonic acidemia and homocystinuria after birth.ConclusionWe present a case of prenatal diagnosis with parental exome sequencing, which successfully diagnosed the carrier status of the fetus and parents in a combined methylmalonic acidemia and homocystinuria family.
Enhancement of sorghum grain yield and nutrition: A role for arbuscular mycorrhizal fungi regardless of soil phosphorus availability
Authors: Watts‐Williams Stephanie J. , Gill Alison R. , Jewell Nathaniel , Brien Christopher J. , Berger Bettina , Tran Binh T. T. , Mace Emma , Cruickshank Alan W. , Jordan David R. , Garnett Trevor , Cavagnaro Timothy R. 
Published: October 2021

Societal Impact StatementSorghum is an important cereal crop that provides calories and nutrients for much of the world's population, and it is often grown with low fertiliser input. Optimising the yield, nutritive content and bioavailability of sorghum grain with minimal input is of importance for human nutrition, and arbuscular mycorrhizal (AM) fungi have previously shown potential to assist in this. Across sorghum genetic diversity, AM fungi improved the yield, nutrition and zinc and iron bioavailability of grain in a low phosphorus soil. Thus, food production systems that effectively manage AM fungi may improve consumer outcomes.Summary

Sorghum is a C4 cereal crop that is an important source of calories and nutrition across the world, predominantly cultivated and consumed in low‐ and middle‐income countries. Sorghum can be highly colonised by arbuscular mycorrhizal (AM) fungi, and the plant‐fungal association can lead to improvements in biomass and nutrient uptake. High‐throughput phenotyping allows us to non‐destructively interrogate the ‘hidden’ effects of AM fungi on sorghum growth and phenology.
Eight genetically diverse sorghum genotypes were grown in a soil amended with 2 or 20 mg P kg−1 and inoculated with an AM fungal culture of Rhizophagus irregularis. High‐throughput phenotyping uncovered the ‘hidden’ effects of AM fungi on growth and phenology, while grain biomass, nutrition, Zn and Fe bioavailability and root AM colonisation was determined after destructive harvest.
Sorghum plants colonised by AM fungi generally performed better than non‐AM control plants, with greater yield, harvest indices, and grain P, Zn and Fe contents. During the early growth stages, AM colonisation led to temporary growth depressions. There were also AM fungal and P fertilisation effects on sorghum time‐of‐flowering. The sorghum genotype with the highest AM colonisation could barely produce grain when non‐inoculated.
The two genotypes that failed to mature had very low AM colonisation. Generally, the genetically diverse sorghum genotypes were highly responsive to AM colonisation and produced more grain of greater nutritive quality when colonised, without adverse consequences for micronutrient bioavailability.
NADH Regeneration Promoted by Solar Light Using Gold Nanoparticles/Layered Double Hydroxides as Novel Photocatalytic Nanoplatforms
Authors: Grosu Elena‐Florentina , Girardon Jean‐Sébastien , Carja Gabriela , Froidevaux Renato 
Published: October 2021

AbstractNicotinamide adenine dinucleotide NAD(P)H is a prolific cofactor in oxidoreductases biochemistry, but its high cost and the stoichiometric amounts motivates significant research for establishing efficient solutions for regenerating NAD(P)H from NAD(P)+. This study presents nanoparticles of gold/layered double hydroxides (AuNPs/LDH) as nanoplatforms with highly efficient photocatalytic response for solar‐light promoted NADH regeneration. The novel photocatalysts are obtained via self‐assembling of ZnAlLDH and AuNPs by using the manifestation of the “structural memory” of the anionic clay in gold salt solution. The chemical composition, structural, optical and nanotextural features of AuNPs/LDH have been assessed by transmission electron microscopy (TEM), energy dispersive X‐Ray Spectroscopy (EDX), powder X‐ray diffraction (XRD), and UV‐Vis Spectroscopy (UV‐Vis). It was found that, at pH 8 and in the presence of flavin mononucleotide (FMN) as a mediator and using water as an electron donor, the regeneration the NADH under solar light is defined by a rate of 20.5 μM/h. Furthermore, the regenerated NADH cofactor is tested in presence of Horseradish Peroxidase (HRP) enzyme to promote the hydrogen peroxide reduction.
Odd entanglement entropy and logarithmic negativity for thermofield double states
Authors: Ghasemi Mostafa , Naseh Ali , Pirmoradian Reza 
Published: October 2021

Abstract
We investigate the time evolution of odd entanglement entropy (OEE) and logarithmic negativity (LN) for the thermofield double (TFD) states in free scalar quantum field theories using the covariance matrix approach. To have mixed states, we choose non-complementary subsystems, either adjacent or disjoint intervals on each side of the TFD. We find that the time evolution pattern of OEE is a linear growth followed by saturation. On a circular lattice, for longer times the finite size effect demonstrates itself as oscillatory behavior. In the limit of vanishing mass, for a subsystem containing a single degree of freedom on each side of the TFD, we analytically find the effect of zero-mode on the time evolution of OEE which leads to logarithmic growth in the intermediate times. Moreover, for adjacent intervals we find that the LN is zero for times t < β/2 (half of the inverse temperature) and after that, it begins to grow linearly. For disjoint intervals at fixed temperature, the vanishing of LN is observed for times t < d/2 (half of the distance between intervals). We also find a similar delay to see linear growth of ∆S = SOEE− SEE. All these results show that the dynamics of these measures are consistent with the quasi-particle picture, of course apart from the logarithmic growth.
Learning and generalising object extraction skill for contact-rich disassembly tasks: an introductory study
Authors: Serrano-Muñoz Antonio , Arana-Arexolaleiba Nestor , Chrysostomou Dimitrios , Bøgh Simon 
Published: October 2021

AbstractRemanufacturing automation must be designed to be flexible and robust enough to overcome the uncertainties, conditions of the products, and complexities in the planning and operation of the processes. Machine learning methods, in particular reinforcement learning, are presented as techniques to learn, improve, and generalise the automation of many robotic manipulation tasks (most of them related to grasping, picking, or assembly). However, not much has been exploited in remanufacturing, in particular in disassembly tasks. This work presents the state of the art of contact-rich disassembly using reinforcement learning algorithms and a study about the generalisation of object extraction skills when applied to contact-rich disassembly tasks. The generalisation capabilities of two state-of-the-art reinforcement learning agents (trained in simulation) are tested and evaluated in simulation, and real world while perform a disassembly task. Results show that at least one of the agents can generalise the contact-rich extraction skill. Besides, this work identifies key concepts and gaps for the reinforcement learning algorithms’ research and application on disassembly tasks.
Genetic and epigenetic characterization of posterior pituitary tumors
Authors: Schmid Simone , Solomon David A. , Perez Eilis , Thieme Anne , Kleinschmidt-DeMasters Bette K. , Giannini Caterina , Reinhardt Annekathrin , Asa Sylvia L. , Mete Ozgur , Stichel Damian , Siewert Christin , Dittmayer Carsten , Hasselblatt Martin , Paulus Werner , Nagel Christoph , Harter Patrick N. , Schittenhelm Jens , Honegger Jürgen , Rushing Elisabeth , Coras Roland , Pfister Stefan M. , Buslei Rolf , Koch Arend , Perry Arie , Jones David T. W. , von Deimling Andreas , Capper David , Lopes M. Beatriz 
Published: October 2021

AbstractPituicytoma (PITUI), granular cell tumor (GCT), and spindle cell oncocytoma (SCO) are rare tumors of the posterior pituitary. Histologically, they may be challenging to distinguish and have been proposed to represent a histological spectrum of a single entity. We performed targeted next-generation sequencing, DNA methylation profiling, and copy number analysis on 47 tumors (14 PITUI; 12 GCT; 21 SCO) to investigate molecular features and explore possibilities of clinically meaningful tumor subclassification. We detected two main epigenomic subgroups by unsupervised clustering of DNA methylation data, though the overall methylation differences were subtle. The largest group (n = 23) contained most PITUIs and a subset of SCOs and was enriched for pathogenic mutations within genes in the MAPK/PI3K pathways (12/17 [71%] of sequenced tumors:FGFR1(3),HRAS(3),BRAF(2),NF1(2),CBL(1),MAP2K2(1),PTEN(1)) and two with accompanyingTERTpromoter mutation. The second group (n = 16) contained most GCTs and a subset of SCOs, all of which mostly lacked identifiable genetic drivers. Outcome analysis demonstrated that the presence of chromosomal imbalances was significantly associated with reduced progression-free survival especially within the combined PITUI and SCO group (p = 0.031). In summary, we observed only subtle DNA methylation differences between posterior pituitary tumors, indicating that these tumors may be best classified as subtypes of a single entity. Nevertheless, our data indicate differences in mutation patterns and clinical outcome. For a clinically meaningful subclassification, we propose a combined histo-molecular approach into three subtypes: one subtype is defined by granular cell histology, scarcity of identifiable oncogenic mutations, and favorable outcome. The other two subtypes have either SCO or PITUI histology but are segregated by chromosomal copy number profile into a favorable group (no copy number changes) and a less favorable group (copy number imbalances present). Both of the latter groups have recurrent MAPK/PI3K genetic alterations that represent potential therapeutic targets.
Absenteeism and associated labour costs according to depressive symptom severity in the German general population: why preventive strategies matter
Authors: Eßl-Maurer Roland , Flamm Maria , Hösl Katharina , Osterbrink Jürgen , van der Zee-Neuen Antje 
Published: October 2021

Abstract
Purpose
Depression is a highly prevalent mental health condition with substantial individual, societal and economic consequences. This study focussed on the association of depressive symptom severity with absenteeism duration and employer labour costs.

Methods
Using cross-sectional data from the German Health Update 2014/2015, multivariable zero-inflated Poisson regression (ZIP) models explored the association of depressive symptom severity (8-item depression patient health questionnaire—PHQ-8), with absenteeism weeks during 12 months in men and women working full- or part-time. The predicted sick leave weeks were multiplied by mean average labour costs.

Results
The sample consisted of 12,405 persons with an average sick leave of 1.89 weeks (SD 4.26). Fifty-four % were women and 57% were between 40 and 59 years of age. In men and women, mild, moderate, moderately severe and severe depressive symptoms were associated with a significant factor increase in sick leave weeks compared to persons with no or minimal symptoms. Labour costs increased with increasing symptom severity from € 1468.22 for men with no or minimal depressive symptoms to € 7190.25 for men with severe depressive symptoms and from € 1045.82 to € 4306.30 in women, respectively.

Conclusion
The present results indicate that increasing depressive symptom severity is associated with increasing absenteeism and employer costs. They emphasize the need for implementation, realignment or extension of professional work-site health promotion programmes aiming at the improvement and maintenance of employee health and the reduction of labour costs associated with depression-related sick leave.
Regional accents modulate perspective in geographical space
Authors: García-Marco Enrique , Branca Itatí , Castillo Dolores , León Inmaculada , Beltrán David , de Vega Manuel 
Published: October 2021

AbstractIn this study, participants listened to first-person statements that mentioned a character who was approaching a geographical location close to (Tenerife, Canary Islands) or distant from the participant (Madrid, Spanish peninsula), pronounced with either the participants' local or a distal regional accent. Participants more often judged approaching statements as coherent when they refer to a close place pronounced with local accent or refer to a distant place with distal accent, rather than when they refer to a close place with distal accent or to a distant place with local accent. These results strongly suggest that the local accent induces listeners to keep their own geographical perspective, whereas the distal accent determines shifting to another’s perspective. In sum, a subtle paralinguistic cue, the speaker’s regional accent, modulates the participants’ geographic perspective when they listen to identical first-person sentences with approaching deictic verbs.