bluuebunny/crossref_metadata_2025_split huggingface dataset:
The WNT1G177C mutation specifically affects skeletal integrity in a mouse model of osteogenesis imperfecta type XV
Authors: Vollersen Nele , Zhao Wenbo , Rolvien Tim , Lange Fabiola , Schmidt Felix Nikolai , Sonntag Stephan , Shmerling Doron , von Kroge Simon , Stockhausen Kilian Elia , Sharaf Ahmed , Schweizer Michaela , Karsak Meliha , Busse Björn , Bockamp Ernesto , Semler Oliver , Amling Michael , Oheim Ralf , Schinke Thorsten , Yorgan Timur Alexander 
Published: November 2021

AbstractThe recent identification of homozygous WNT1 mutations in individuals with osteogenesis imperfecta type XV (OI-XV) has suggested that WNT1 is a key ligand promoting the differentiation and function of bone-forming osteoblasts. Although such an influence was supported by subsequent studies, a mouse model of OI-XV remained to be established. Therefore, we introduced a previously identified disease-causing mutation (G177C) into the murine Wnt1 gene. Homozygous Wnt1G177C/G177C mice were viable and did not display defects in brain development, but the majority of 24-week-old Wnt1G177C/G177C mice had skeletal fractures. This increased bone fragility was not fully explained by reduced bone mass but also by impaired bone matrix quality. Importantly, the homozygous presence of the G177C mutation did not interfere with the osteoanabolic influence of either parathyroid hormone injection or activating mutation of LRP5, the latter mimicking the effect of sclerostin neutralization. Finally, transcriptomic analyses revealed that short-term administration of WNT1 to osteogenic cells induced not only the expression of canonical WNT signaling targets but also the expression of genes encoding extracellular matrix modifiers. Taken together, our data demonstrate that regulating bone matrix quality is a primary function of WNT1. They further suggest that individuals with WNT1 mutations should profit from existing osteoanabolic therapies.
Circ-SIRT1 inhibits cardiac hypertrophy via activating SIRT1 to promote autophagy
Authors: Wang Weichen , Wang Longlong , Yang Mengyue , Wu Chunwei , Lan Rui , Wang Weiwei , Li Yuze 
Published: November 2021

AbstractMounting studies have substantiated that abrogating autophagy contributes to cardiac hypertrophy (CH). Sirtuin 1 (SIRT1) has been reported to support autophagy and inhibit CH. However, the upstream regulation mechanism behind the regulation of SIRT1 level in CH remains unclear. Circular RNAs (circRNAs) are vital modulators in diverse human diseases including CH. This study intended to investigate the regulatory mechanism of circRNA on SIRT1 expression in CH. CH model was established by angiotensin II (Ang II) fusion or transverse aortic constriction (TAC) surgery and Ang II treatment on hiPSC-CMs and H9c2 cells in vitro. Our results showed that circ-SIRT1 (hsa_circ_0093884) expression was downregulated in Ang II-treated hiPSC-CMs, and confirmed that its conserved mouse homolog circ-Sirt1 (mmu_circ_0002354) was expressed at low levels in Ang II-treated H9c2 cells and TAC-induced mice model. Functionally, circ-SIRT1/circ-Sirt1 attenuated Ang II-induced CH and induced autophagy in hiPSC-CMs and H9c2 cardiomyocytes. Mechanistically, circ-SIRT1 could upregulate its host gene SIRT1 at the post-transcriptional level by sponging miR-3681-3p/miR-5195-3p and stabilized SIRT1 protein at the post-translational level by recruiting USP22 to induce deubiquitination on SIRT1 protein. Further, SIRT1 knockdown could rescue the effect of circ-SIRT1 upregulation on Ang II-induced CH and autophagy in vitro and in vivo. In conclusion, we first uncovered that circ-SIRT1 restrains CH via activating SIRT1 to promote autophagy, indicating circ-SIRT1 as a promising target to alleviate CH.
Swiprosin-1 deficiency in macrophages alleviated atherogenesis
Authors: Tong Ling-Chang , Wang Zhi-Bin , Zhang Jia-Qi , Wang Yue , Liu Wei-Ye , Yin Hao , Li Jia-Cheng , Su Ding-Feng , Cao Yong-Bing , Zhang Li-Chao , Li Ling 
Published: November 2021

AbstractMacrophages play a vital role in the development of atherosclerosis. Previously, we have found that swiprosin-1 was abundantly expressed in macrophages. Here, we investigated the role of swiprosin-1 expressed in macrophages in atherogenesis. Bone marrow transplantation was performed from swiprosin-1-knockout (Swp−/−) mice and age-matched ApoE−/− mice. Atherosclerotic lesion, serum lipid, and interleukin-β (IL-β) levels were detected. In vitro, the peritoneal macrophages isolated from Swp−/− and wild-type mice were stimulated with oxidized low-density lipoprotein (ox-LDL) and the macrophage of foam degree, cellular lipid content, apoptosis, inflammatory factor, migration, and autophagy were determined. Our results showed that swiprosin-1 was mainly expressed in macrophages of atherosclerotic plaques in aorta from ApoE−/− mice fed with high-cholesterol diet (HCD). The expression of swiprosin-1 in the foaming of RAW264.7 macrophages gradually increased with the increase of the concentration and time stimulated with ox-LDL. Atherosclerotic plaques, accumulation of macrophages, collagen content, serum total cholesterol, LDL, and IL-β levels were decreased in Swp−/− → ApoE−/− mice compared with Swp+/+ → ApoE−/− mice fed with HCD for 16 weeks. The macrophage foam cell formation and cellular cholesterol accumulation were reduced, while the lipid uptake and efflux increased in macrophages isolated from Swp−/− compared to wild-type mice treated with ox-LDL. Swiprosin-1 deficiency in macrophages could inhibit apoptosis, inflammation, migration, and promote autophagy. Taken together, our results demonstrated that swiprosin-1 deficiency in macrophages could alleviate the development and progression of AS. The role of swiprosin-1 may provide a promising new target for ameliorating AS.
Elevated circulating follistatin associates with an increased risk of type 2 diabetes
Authors: Wu Chuanyan , Borné Yan , Gao Rui , López Rodriguez Maykel , Roell William C. , Wilson Jonathan M. , Regmi Ajit , Luan Cheng , Aly Dina Mansour , Peter Andreas , Machann Jürgen , Staiger Harald , Fritsche Andreas , Birkenfeld Andreas L. , Tao Rongya , Wagner Robert , Canouil Mickaël , Hong Mun-Gwan , Schwenk Jochen M. , Ahlqvist Emma , Kaikkonen Minna U. , Nilsson Peter , Shore Angela C. , Khan Faisel , Natali Andrea , Melander Olle , Orho-Melander Marju , Nilsson Jan , Häring Hans-Ulrich , Renström Erik , Wollheim Claes B. , Engström Gunnar , Weng Jianping , Pearson Ewan R. , Franks Paul W. , White Morris F. , Duffin Kevin L. , Vaag Allan Arthur , Laakso Markku , Stefan Norbert , Groop Leif , De Marinis Yang 
Published: November 2021

AbstractThe hepatokine follistatin is elevated in patients with type 2 diabetes (T2D) and promotes hyperglycemia in mice. Here we explore the relationship of plasma follistatin levels with incident T2D and mechanisms involved. Adjusted hazard ratio (HR) per standard deviation (SD) increase in follistatin levels for T2D is 1.24 (CI: 1.04–1.47, p < 0.05) during 19-year follow-up (n = 4060, Sweden); and 1.31 (CI: 1.09–1.58, p < 0.01) during 4-year follow-up (n = 883, Finland). High circulating follistatin associates with adipose tissue insulin resistance and non-alcoholic fatty liver disease (n = 210, Germany). In human adipocytes, follistatin dose-dependently increases free fatty acid release. In genome-wide association study (GWAS), variation in the glucokinase regulatory protein gene (GCKR) associates with plasma follistatin levels (n = 4239, Sweden; n = 885, UK, Italy and Sweden) and GCKR regulates follistatin secretion in hepatocytes in vitro. Our findings suggest that GCKR regulates follistatin secretion and that elevated circulating follistatin associates with an increased risk of T2D by inducing adipose tissue insulin resistance.
Deep Bayesian local crystallography
Authors: Kalinin Sergei V. , Oxley Mark P. , Valleti Mani , Zhang Junjie , Hermann Raphael P. , Zheng Hong , Zhang Wenrui , Eres Gyula , Vasudevan Rama K. , Ziatdinov Maxim 
Published: November 2021

AbstractThe advent of high-resolution electron and scanning probe microscopy imaging has opened the floodgates for acquiring atomically resolved images of bulk materials, 2D materials, and surfaces. This plethora of data contains an immense volume of information on materials structures, structural distortions, and physical functionalities. Harnessing this knowledge regarding local physical phenomena necessitates the development of the mathematical frameworks for extraction of relevant information. However, the analysis of atomically resolved images is often based on the adaptation of concepts from macroscopic physics, notably translational and point group symmetries and symmetry lowering phenomena. Here, we explore the bottom-up definition of structural units and symmetry in atomically resolved data using a Bayesian framework. We demonstrate the need for a Bayesian definition of symmetry using a simple toy model and demonstrate how this definition can be extended to the experimental data using deep learning networks in a Bayesian setting, namely rotationally invariant variational autoencoders.
Rare phenotype: Hand preaxial polydactyly associated with LRP6-related tooth agenesis in humans
Authors: Zhang Liutao , Yu Miao , Sun Kai , Fan Zhuangzhuang , Liu Haochen , Feng Hailan , Liu Yang , Han Dong 
Published: November 2021

AbstractLow-density lipoprotein receptor-related protein 6 (LRP6) is a pathogenic gene of selective tooth agenesis-7 (OMIM#616724). Although the malformation of the digits and fore- and hindlimbs has been reported inLrp6-deficient mice, it has been rarely discovered in humans withLRP6mutations. Here, we demonstrate an unreported autosomal dominantLRP6heterozygous mutation (c.2840 T > C;p.Met947Thr) in a tooth agenesis family with hand polydactyly, and another unreported autosomal dominantLRP6heterozygous mutation (c.1154 G > C;p.Arg385Pro) in a non-syndromic tooth agenesis family. Bioinformatic prediction demonstrated the deleterious effects of the mutations, and LRP6 structure changes suggested the corresponding functional impairments. Analysis on the pattern ofLRP6-related tooth agenesis demonstrated the maxillary lateral incisor was the most affected. Our study report thatLRP6mutation might be associated with hand preaxial polydactyly in humans, which broaden the phenotypic spectrum ofLRP6-related disorders, and provide valuable information on the characteristics ofLRP6-related tooth agenesis.
Universal size-dependent nonlinear charge transport in single crystals of the Mott insulator Ca2RuO4
Authors: Avallone G. , Fermin R. , Lahabi K. , Granata V. , Fittipaldi R. , Cirillo C. , Attanasio C. , Vecchione A. , Aarts J. 
Published: November 2021

AbstractThe surprisingly low current density required for inducing the insulator to metal transition has made Ca2RuO4 an attractive candidate material for developing Mott-based electronics devices. The mechanism driving the resistive switching, however, remains a controversial topic in the field of strongly correlated electron systems. Here we probe an uncovered region of phase space by studying high-purity Ca2RuO4 single crystals, using the sample size as principal tuning parameter. Upon reducing the crystal size, we find a four orders of magnitude increase in the current density required for driving Ca2RuO4 out of the insulating state into a non-equilibrium phase which is the precursor to the fully metallic phase. By integrating a microscopic platinum thermometer and performing thermal simulations, we gain insight into the local temperature during simultaneous application of current and establish that the size dependence is not a result of Joule heating. The findings suggest an inhomogeneous current distribution in the nominally homogeneous crystal. Our study calls for a reexamination of the interplay between sample size, charge current, and temperature in driving Ca2RuO4 towards the Mott insulator to metal transition.
The Spanish gut microbiome reveals links between microorganisms and Mediterranean diet
Authors: Latorre-Pérez Adriel , Hernández Marta , Iglesias Jose Ramón , Morán Javier , Pascual Javier , Porcar Manuel , Vilanova Cristina , Collado Luis 
Published: November 2021

AbstractDespite the increasing evidence of links between human gut and health, the number of gut microbiomes that have been studied to date at a country level are surprisingly low. Mediterranean countries, including some of the most long-lived and healthy countries in the world, have not been considered so far in those studies at a large scale. The main objective of this work is to characterize the gut microbiome of a healthy adult population of a Mediterranean, paradigmatically healthy country: Spain. Stool samples from 530 healthy volunteers were collected, total metagenomic DNA extracted, and the microbial profiles determined through 16S rRNA metataxonomic sequencing. Our results confirm the associations between several microbial markers and different variables, including sex, age, BMI and diet choices, and bring new insights into the relationship between microbiome and diet in the Spanish population. Remarkably, some of the associations found, such as the decrease of Faecalibacterium with age or the link of Flavonifractor with less healthy dietary habits, have been barely noticed in other large-scale cohorts. On the other hand, a range of links between microorganisms, diet, and lifestyle coincide with those reported in other populations, thus increasing the robustness of such associations and confirming the importance of these microbial markers across different countries. Overall, this study describes the Spanish “normal” microbiome, providing a solid baseline for future studies investigating the effects of gut microbiome composition and deviations in the adherence to the Mediterranean diet.
Animal models of Parkinson’s disease: a guide to selecting the optimal model for your research
Authors: Lama Joana , Buhidma Yazead , Fletcher Edward J.R. , Duty Susan 
Published: November 2021

Abstract
Parkinson’s disease (PD) is a complex, multisystem disorder characterised by α-synuclein (SNCA) pathology, degeneration of nigrostriatal dopaminergic neurons, multifactorial pathogenetic mechanisms and expression of a plethora of motor and non-motor symptoms. Animal models of PD have already been instructive in helping us unravel some of these aspects. However, much remains to be discovered, requiring continued interrogation by the research community. In contrast with the situation for many neurological disorders, PD benefits from of a wide range of available animal models (pharmacological, toxin, genetic and α-synuclein) but this makes selection of the optimal one for a given study difficult. This is especially so when a study demands a model that displays a specific combination of features. While many excellent reviews of animal models already exist, this review takes a different approach with the intention of more readily informing this decision-making process. We have considered each feature of PD in turn – aetiology, pathology, pathogenesis, motor dysfunctions and non-motor symptoms (NMS) – highlighting those animal models that replicate each. By compiling easily accessible tables and a summary figure, we aim to provide the reader with a simple, go-to resource for selecting the optimal animal model of PD to suit their research needs.
A transformer generative adversarial network for multi‐track music generation
Authors: Jin Cong , Wang Tao , Li Xiaobing , Tie Chu Jie Jiessie , Tie Yun , Liu Shan , Yan Ming , Li Yongzhi , Wang Junxian , Huang Shenze 
Published: November 2021

AbstractThis study proposes a new generation network based on transformers and guided by the music theory to produce high‐quality music work. In this study, the decoding block of the transformer is used to learn the internal information of single‐track music, and cross‐track transformers are used to learn the information amongst the tracks of different musical instruments. A reward network based on the music theory is proposed, which optimizes the global and local loss objective functions while training and discriminating the network so that the reward network can provide a reliable adjustment method for the generation of the network. The method of combining the reward network and cross entropy loss is used to guide the training of the generator and produce high‐quality music work. Compared with other multi‐track music generation models, the experimental results verify the validity of the model.
Risk Patterns of Distant Metastases in Follicular, Papillary and
Medullary Thyroid Cancer
Authors: Machens Andreas , Lorenz Kerstin , Weber Frank , Dralle Henning 
Published: November 2021

AbstractThis study of 542 patients with follicular thyroid cancer, 366 patients with the
follicular variant and 1452 patients with the classical variant of papillary
thyroid cancer, and 819 patients with sporadic medullary thyroid cancer operated
at a tertiary referral center aimed to determine risk patterns of distant
metastasis for each tumor entity, which are ill-defined. On multivariable
logistic regression analyses, lymph node metastasis consistently emerged as an
independent risk factor of distant metastasis, yielding odds ratios (ORs) of 2.4
and 2.8 for follicular thyroid cancer and the follicular variant of papillary
thyroid cancer, and ORs of 5.9 and 6.4 for the classical variant of papillary
thyroid cancer and sporadic medullary thyroid cancer. Another independent risk
factor consistently associated with distant metastasis, most strongly in
follicular thyroid cancer and the follicular variant of papillary thyroid cancer
(OR 3.5 and 4.0), was patient age >60 years. Altogether, 2 distinct risk
patterns of distant metastasis were identified, which were modulated by other
cancer type-dependent risk factors: one with lymph node metastasis as leading
component (classical variant of papillary thyroid cancer and sporadic medullary
thyroid cancer), and another one with age as leading component (follicular
thyroid cancer and the follicular variant of papillary thyroid cancer). Distant
metastasis was exceptional in node-negative patients with sporadic medullary
thyroid cancer (1.7%) and the classical variant of papillary thyroid
cancer (1.4%), and infrequent in node-negative patients with the
follicular variant of papillary thyroid cancer (4.4%). These findings
delineate windows of opportunity for early surgical intervention before distant
metastasis has occurred.
An Important Potential Anti-Epileptic/Anticonvulsant Active
Group: A Review of 1,2,4-Triazole Groups and Their Action
Authors: Wang Ying , Liu Dachuan 
Published: November 2021

AbstractEpilepsy is one of the most common encountered neurological disorders. Many
individuals continue to have seizures despite medical and surgical treatments,
suggesting new antiepileptic/anticonvulsant drugs are required. Triazole
compounds are widely used in pharmaceuticals and have gained significant
importance in medicinal chemistry. This article is an attempt to systematically
review the research of triazole derivatives in the design and development of
anticonvulsant agents during the past two decades through extensive literature
research. The results show that triazole occupy a distinct niche in heterocyclic
chemistry and represent a key motif in medicinal chemistry because of their
capability to exhibit an array of properties and bioactivities, Therefore,
1,2,4-triazole seems to be an important pharmacophore, especially in the field
of antiepileptic, which is of great explored potentiality and utilized value.
Through in-depth research on this type of structure, it is believed that more
1,2,4-triazole compounds will be developed as anti-epileptic drugs for clinical
use.
Single Ophthalmology Program Trends in Resident Surgical and Research Productivity by Gender, Underrepresented Minority Status, and Welcoming a Child
Authors: Kong Alan W. , Schallhorn Julie M. , Ou Yvonne 
Published: November 2021

Abstract
Objective The aim of the study is to identify differences for cataract surgery, total procedural volume, and publication rates between residents by gender, underrepresented minority (URM) status, and welcoming a child during ophthalmology residency.
Design This is a retrospective, cross-sectional study.
Participants A total of 89 residents graduating from 2002 to 2020 at a single program were included.
Methods A multiple linear regression model was created to determine factors predictive of the number of cataract surgeries performed as the primary surgeon, total procedural volume, number of publications, or first author publications. Independent variables included resident gender, URM status, PhD degree, welcoming a child during residency, and graduation year.
Results Of the 89 graduating residents included in this study, identifying as female (45 women, 50.6%) and as URM (eight identifying as URM, 9.0%) was not associated with a difference in surgical or research volume. Female residents performed a mean (SD) of 240.1 (55.1) cataract surgeries while male residents performed 210.6 (46.1) cataract surgeries. Residents identifying as URM completed 228.1 (41.9), while non-URM residents completed 234.8 (51.9) cataract surgeries. Since 2008, eight female residents (22.2%) and two male residents (6.9%) added children to their families. Welcoming a child to the family was also not associated with decreased surgical or publication volume. Number of cataract surgeries, total procedures, and number of publications did increase over time (p <0.001), as each graduation year was associated with 5.4 (95% CI: 3.9, 7.1) more cataract surgeries and 30.5 (95% CI: 25.7, 36.9) more procedures. Each year was also associated with 0.24 (95% CI: 0.09, 0.38) more publications and 0.18 (95% CI: 0.08, 0.28) more first author publications.
Conclusion Surgical and research productivity has increased, and female residents and residents who identify as URM did not have fewer cataract surgeries or procedures. Welcoming a child also did not correlate with differences in surgical or procedural volume. Programs should continue to promote equitable surgery and procedural distributions as well as identify more targeted strategies to encourage and recruit underrepresented medical students into ophthalmology.
Secondary Dentin as an Aid in Gender Predilection: A Forensic Study
Authors: Singh Himanshu , Patel Vedant , Razdan Rahul A. , Jha Deepak , Nayak Prachi , Nayak Sushruth 
Published: November 2021

Abstract
Background Forensic odontology deals with age, sex, and race determination of the deceased at crime scenes, disasters, or natural calamities. Studies regarding the role of secondary dentin in age estimation have been documented on a several occasions in the literature but use of secondary dentin in gender predilection has not yet been documented. So, the present study was aimed at using the secondary dentin as a diagnostic tool in gender predilection.
Materials and Methods The study included a total of 20 samples (10 males and 10 females). Extracted teeth were collected and placed in 10% neutral buffered formalin solution. The sections were ground on Arkansas stone until the appropriate thickness of the ground sections was achieved. The freshly prepared ground section was mounted on a slide using DPX mounting media. Ground sections were visualized under a microscope and the thickness of secondary dentine was measured using the image analysis software.
Results The data were collected and subjected to group statistics. The secondary dentin thickness of all the samples, males and females, was measured. It was observed in our study that the mean thickness of secondary dentin was more in male samples (0.2970) with the standard deviation of 0.01494, as compared with that of females where the mean thickness was found to be 0.1970 with the standard deviation of 0.02058.
Conclusion This study has shown that variation in secondary dentin thickness does exist between male and female groups. This criterion can be considered as an aid for gender determination in the future.