bluuebunny/crossref_metadata_2025_split huggingface dataset:
Shared Genetic Loci For Body Fat Storage And Adipocyte Lipolysis In Humans
Authors: Kulyté Agné , Lundbäck Veroniqa , Arner Peter , Strawbridge Rona J. , Dahlman Ingrid 
Published: September 2021

Abstract
Background. Total body fat and central fat distribution are heritable traits and well-established predictors of adverse metabolic outcomes. Lipolysis is the process responsible for the hydrolysis of triacylglycerols stored in adipocytes. To increase our understanding of the genetic regulation of body fat distribution and total body fat, we set out to determine if genetic variants associated with body mass index (BMI) or waist-hip-ratio adjusted for BMI (WHRadjBMI) in genome-wide association studies (GWAS) mediate their effect by influencing adipocyte lipolysis.Methods. We utilized data from the recent GWAS of spontaneous and isoprenaline-stimulated lipolysis in the unique GENetics of Adipocyte Lipolysis (GENiAL) cohort. GENiAL consists of 939 participants who have undergone abdominal subcutaneous adipose biopsy for the determination of spontaneous and isoprenaline-stimulated lipolysis in adipocytes. Results. We report 11 BMI and 15 WHRadjBMI loci with SNPs displaying nominal association with lipolysis and allele-dependent gene expression in adipose tissue according to in silico analysis. Functional evaluation of candidate genes in these loci by small interfering RNAs (siRNA)-mediated knock-down in adipose-derived stem cells identified ZNF436 and NUP85 as intrinsic regulators of lipolysis consistent with the associations observed in the clinical cohorts. Furthermore, candidate genes in another BMI-locus (STX17) and two more WHRadjBMI loci (NID2, GGA3, GRB2) control lipolysis alone, or in conjunction with lipid storage, and may hereby be involved in genetic control of body fat.Conclusions. The findings expand our understanding of how genetic variants mediate their impact on the complex traits of fat storage and distribution.
CompoNet: Toward Incorporating Human Perspective in Automatic Music Generation Using Deep Learning
Authors: HekmatiAthar SeyyedPooya , Anwar Mohd 
Published: September 2021

Abstract
The art nature of music makes it difficult, if not impossible, to extract solid rules from composed pieces and express them mathematically. This has led to the lack of utilization of music expert knowledge in the AI literature for automation of music composition. In this study, we employ intervals, which are the building blocks of music, to represent musical data closer to human composers’ perspectives. Based on intervals, we developed and trained OrchNet which translates musical data into and from numerical vector representation. Another model called CompoNet is developed and trained to generate music. Using intervals and a novel monitor-and-inject mechanism, we address the two main limitations of the literature: lack of orchestration and lack of long-term memory. The music generated by CompoNet is evaluated by Turing Test: whether human judges can tell the difference between the music pieces composed by humans versus. generated by our system. The Turing test results were compared using Mann-Whitney U Test, and there was no statistically significant difference between human-composed music versus what our system has generated.
A Comprehensive Study of Microsatellite Instability Testing And Its Comparison With Immunohistochemistry In Gastric And Colorectal Cancers
Authors: Park Yujun , Nam Soo Kyung , Seo Soo Hyun , Park Kyoung Un , Ahn Sang-Hoon , Oh Heung-Kwon , Kim Duck-Woo , Park Do Joong , Kang Sung-Bum , Kim Hyung-Ho , Lee Hye Seung 
Published: September 2021

Abstract
Background Microsatellite instability (MSI) testing was comprehensively analyzed and compared with immunohistochemistry (IHC) for the mismatch repair (MMR) protein in gastric cancer (GC) and colorectal cancer (CRC). Methods PCR-based MSI testing was performed to compare the tumor and non-neoplastic normal tissues using five microsatellites consisting of two mononucleotide (BAT-26, BAT-25) and three dinucleotide (D5S346, D2S123, and D17S250) in 5,676 GC and 2,553 CRC cases. IHC for the MMR protein MLH1 was done in GCs, and IHC for four MMR proteins (MLH1, MSH2, MSH6, and PMS2) was performed in CRCs. Reviews were carried out for discordant or indeterminate IHC cases (such as focal loss of expression, equivocal expression, or abnormal expression patterns). Results MSI-high (MSI-H) and MMR-deficient (dMMR) expression was observed in 521 (9.2%) GC and 171 (6.7%) CRC cases. Discordance between MSI testing and IHC as well as indeterminate IHC cases accounted for 54 (0.9%) and 29 (1.1%) cases out of all GC and CRC cases, respectively, but accounted for 9.4% and 14.1% out of 575 GC and 205 CRC cases, respectively, excluding unequivocal microsatellite stable/MSI-low and MMR-proficient (pMMR) expression cases. pMMR expression was observed in most of the MSI-H GCs and CRCs consisting of only one unstable BAT-25 mononucleotide marker or solely of dinucleotide markers. ConclusionsConsidering the low incidence of MSI-H or dMMR expression, discordant or indeterminate IHC and/or MSI results were occasionally identified in GC and CRC cases, requiring complementary testing. These findings provide evidence for MSI testing and MMR IHC in routine clinical practice.
Deep learning methods improve polygenic risk analysis and prediction for Alzheimer’s disease
Authors: Zhou Xiaopu , Chen Yu , Ip Fanny , Jiang Yuanbing , Cao Han , Zhong Huan , Chen Jiahang , Ye Tao , Chen Yuewen , Zhang Yulin , Ma Shuangshuang , Lo Ronnie , Tong Estella , Initiative Alzheimer’s Disease Neuroimaging Initiative Alzheimer’s Dise , Mok Vincent , Kwok Timothy , Guo Qihao , Mok Kin , Shoai Maryam , Hardy John , Chen Lei , Fu Amy , Ip Nancy 
Published: September 2021

Abstract
Recent advances in genetic sequencing have enabled comprehensive genetic analyses of human diseases, resulting in the identification of numerous genetic risk factors for heritable disorders including Alzheimer’s disease (AD). Such analyses enable AD risk prediction well before disease onset, which is critical for early interventions. However, current analytical approaches have limited ability to accurately estimate the risk effects of genetic variants owing to epistatic effects, which have been overlooked in most previous studies, resulting in unsatisfactory disease risk prediction. Herein, we modeled AD polygenic risk using deep learning methods, which outperformed existing models (i.e., weighted polygenic risk score and lasso models) for classifying disease risk. Moreover, by examining the associations between the outcomes from deep learning methods and multi-omics data obtained from our in-house Chinese AD cohorts, we identified the pathways that are potentially regulated by AD polygenic risk, including immune-associated signaling pathways. Thus, our results demonstrate the utility of deep learning methods for modeling the genetic risks of human diseases, which can facilitate both disease risk classification and the study of disease mechanisms.
Post-traumatic Peripheral Vestibular Disorders (Excluding Positional Vertigo): Institutional Experience from University Health Network’s Workplace Safety and Insurance Board Head-Injury Program
Authors: Misale Priyanka , hassannia fatemeh , Dabiri Sasan , Brandstaetter Tom , Rutka John 
Published: September 2021

Abstract
Purpose: Benign paroxysmal positional vertigo has typically been reported to be the most common cause of post-traumatic dizziness. There is however paucity in the literature about other peripheral vestibular disorders post-head injury. This article provides an overview of other causes of non-positional dizziness post-head trauma from our large institutional experience.Methods: The UHN WSIB Neurotology database (n=4,291) between 1998 and 2018 was retrospectively studied for those head-injured workers presenting with non-positional peripheral vestibular disorders. All subjects had a detailed neurotological history and examination and vestibular testing including video nystagmography, video head impulse testing (or a magnetic scleral search coil study), vestibular-evoked myogenic potentials, and audiometry. Imaging studies included routine brain and high-resolution temporal bone CT scans and/or brain MRI.Results: Based on a database of 4,291 head-injured workers with dizziness, 244 were diagnosed with non-positional peripheral vertigo. Recurrent vestibulopathy (RV) was the most common cause of non-positional post-traumatic vertigo. The incidence of Meniere’s disease in the post-traumatic setting did not appear greater than found in the general population. Conclusion: The clinical spectrum pertaining to recurrent vestibulopathy, Meniere’s disease, delayed endolymphatic hydrops, drop attacks, superior semicircular canal dehiscence syndrome, and uncompensated peripheral vestibular loss are discussed.
Machine Learning-based Model for Prediction of Clinical Deterioration in Hospitalized Patients by COVID-19.
Authors: Garcia-Gutierrez Susana , Esteban-Aizpiri Cristobal , Lafuente Iratxe , Barrio Irantzu , Quiros Raul , Quintana Jose M , Uranga Ane , Group. COVID-REDISSEC Working 
Published: September 2021

Abstract
Background

Despite the publication of great number of tools to aid decisions in COVID-19 patients, there is a lack of good instruments to predict clinical deterioration.
Methods

COVID19-Osakidetza is a prospective cohort study recruiting COVID-19 patients. We collected information from baseline to discharge on: sociodemographic characteristics, comorbidities and associated medications, vital signs, treatment received and lab test results. Outcome was need for intensive ventilatory support (with at least standard high-flow oxygen face mask with a reservoir bag for at least 6 hours and need for more intensive therapy afterwards or Optiflow™ high-flow nasal cannula or noninvasive or invasive mechanical ventilation) and/or admission to a critical care unit and/or death during hospitalization. We developed a Catboost model summarizing the findings using Shapley Additive Explanations. Performance of the model was assessed using area under the receiver operating characteristic and prediction recall curves (AUROC and AUPRC respectively) and calibrated using the Hosmer-Lemeshow test.
Results

Overall, 1568 patients were included in the derivation cohort and 956 in the (external) validation cohort. The percentages of patients who reached the composite endpoint were 23.3% vs 20% respectively. The strongest predictors of clinical deterioration were arterial blood oxygen pressure, followed by age, levels of several markers of inflammation (procalcitonin, LDH, CRP) and alterations in blood count and coagulation. Some medications, namely, ATC AO2 (antiacids) and N05 (neuroleptics) were also among the group of main predictors, together with C03 (diuretics). In the validation set, the CatBoost AUROC was 0.79, AUPRC 0.21 and Hosmer-Lemeshow test statistic 0.36.
Conclusions

We present a machine learning-based prediction model with excellent performance properties to implement in EHRs. Our main goal was to predict progression to a score of 5 or higher on the WHO Clinical Progression Scale before patients required mechanical ventilation. Future steps are to externally validate the model in other settings and in a cohort from a different period and to apply the algorithm in clinical practice.
Tocilizumab in Hospitalized Patients with Severe COVID-19: An Open Label, Prospective Study
Authors: Karampitsakos Theodoros , Malakounidou Elli , Papaioannou Ourania , Dimakopoulou Vasilina , Zarkadi Eirini , Katsaras Matthaios , Tsiri Panagiota , Tsirikos Georgios , Georgiopoulou Vasiliki , Oikonomou Ioanna , Davoulos Christos , Velissaris Dimitrios , Sampsonas Fotios , Marangos Markos , Akinosoglou Karolina , Tzouvelekis Argyris 
Published: September 2021

Abstract
Background: Data on the safety and efficacy profile of tocilizumab in patients with severe COVID-19 needs to be enriched.Methods: In this open label, prospective study, we evaluated clinical outcomes in consecutive patients with COVID-19 and PaO2/FiO2<200 receiving tocilizumab plus usual care versus usual care alone. The primary outcome was 28-day mortality. Secondary outcomes included time to discharge, change in PaO2/FiO2 at day 5 and change in WHO progression scale at day 10.Findings: Overall, 114 patients were included in the analysis (tocilizumab plus usual care: 56, usual care: 58). Allocation to usual care was associated with significant increase in 28-day mortality compared to tocilizumab plus usual care [Cox proportional-hazards model: HR: 3.34, (95%CI: 1.21 to 9.30), (p=0.02)]. There was not a statistically significant difference with regards to hospital discharge over the 28-day period for patients receiving tocilizumab compared to usual care [11.0 days (95%CI: 9.0 to 16.0) vs 14.0 days (95%CI: 10.0 to 24.0), HR: 1.32 (95%CI: 0.84 to 2.08), p=0.21]. ΔPaO2/FiO2 at day 5 was significantly higher in the tocilizumab group compared to the usual care group [42.0 (95%CI: 23.0 to 84.7) vs 15.8 (95%CI: -19.4 to 50.3), p=0.03]. ΔWHO scale at day 10 was significantly lower in the tocilizumab group compared to the usual care group (-0.5±2.1 vs 0.6±2.6, p=0.005). Conclusion: This is the first study administrating tocilizumab in patients with COVID-19 based on PaO2/FiO2. Tocilizumab improved survival and other clinical outcomes in hospitalized patients with COVID-19 and PaO2/FiO2<200 irrespective of systemic inflammatory markers levels.
Medical Educators’ Experiences On Medically Unexplained Symptoms and Intercultural Communication—An Expert Focus Group Study
Authors: Sallay Viola , Martos Tamás , Lucza Lilla , Weiland Anne , Stegers‐Jager Karen M. , Vermeir Peter , Mariman An Noelle Margareta , Csabai Márta 
Published: September 2021

Abstract
Background

Medically unexplained symptoms (MUS) are highly prevalent and remain challenging in healthcare and medical education, along with the increase in the importance of intercultural issues regarding MUS. However, less is known about the challenges of professionally addressing patients with MUS in the interprofessional and intercultural contexts. Thus, the present study aims to provide the first exploration of the experiences of medical specialists regarding treating MUS in intercultural contexts and inputs for training development on the intercultural aspects of MUS.
Methods

Three focus groups (total n = 13) consisting of medical specialists from a Hungarian university who were teaching at the medical faculty in intercultural settings and also worked for the university health services were interviewed. The topics covered the participants' personal experiences on addressing MUS and the challenges of intercultural communication and the intercultural educational context. Thematic analysis was used to yield a qualitative account of the interviews as guided by the research questions.
Results

Representing the different aspects of medical specialists, the study identified three main themes in the experiences of medical specialists, namely, 1) the need to adapt to the personal world of patients and search for common frames to understand MUS, 2) the need to discover methods for adapting to cultural differences and 3) the need to enhance the interprofessional coordination of knowledge and practices.
Conclusions

The results are in line with the distinct conclusions of previous studies. Moreover, an integrated educational program on the intercultural aspects of MUS may address the main themes separately and, subsequently, support their integration. Therefore, the study discusses the manner in which an integrated educational program on the intercultural aspects of MUS may address the needs recognized in these aspects.
Topological phase transition and charge-spin coupling in the kagome metal YMn6Sn6
Authors: Siegfried Peter , Bhandari Hari , Jones D , Ghimire Madhav , Dally Rebecca , Poudel L , Bleuel M , Lynn Jeffrey , Mazin Igor , Ghimire Nirmal 
Published: September 2021

Abstract
The Fermi surface (FS) is essential for understanding the properties of metals. It can change under both conventional symmetry-breaking phase transitions and Lifshitz transitions (LTs), where the FS, but not the crystal symmetry, changes abruptly. Magnetic phase transitions involving uniformly rotating spin textures are conventional in nature, requiring strong spin-orbit coupling (SOC) to influence the FS topology and generate measurable properties. LTs driven by a continuously varying magnetization are rarely discussed. Here we present two such manifestations in the magnetotransport of the kagome magnet YMn6Sn6; one caused by changes in the magnetic structure and another by a magnetization-driven LT. The former yields a 10% magnetoresistance enhancement without a strong SOC, while the latter a 45% reduction in the resistivity. These phenomena offer a unique view into the interplay of magnetism and electronic topology, crucial for understanding the rare-earth counterparts, such as TbMn6Sn6, recently shown to harbor novel correlated topological physics.
Effective Capacity Analysis of Reconfigurable Intelligent Surfaces Aided NOMA Network
Authors: Li Geng , Liu Huiling , Huang Gaojian , Li Xingwang , Raj Bichu , Kara Ferdi 
Published: September 2021

Abstract
The future sixth generation (6G) is going to face the significant challenges of massive connections and green communication. Recently, reconfigurable intelligent surfaces (RIS) and non-orthogonal multiple access (NOMA) have been proposed as two key technologies to address the above problems. Motivated by this fact, we consider a downlink RIS-aided NOMA system, where the base station seeks to communicate with two NOMA users with the aid of a RIS. Considering future network supporting real-time service, we investigate the system performance with the view of effective capacity (EC), which is an important evaluation metric of sensitive to delay sensitive system. Based on this basis, we derive the analytical expressions of the EC of the near and far users. To obtain more useful insights, we deduce the analytical approximation expressions of the EC in the low signal-to-noise-ratio (SNR) approximation by utilizing Taylor expansion. In order to compare, we provide the results of orthogonal multiple access (OMA). It is found that 1) The number of RIS components and the transmission power of the base station have important effects on the performance of the considered system model. 2) Compared with OMA, NOMA system has higher effective capacity due to the short transmission time.
Integrated Halo Model And Hydrodynamic Simulation For Optimization Oil Production In Crystalline Fractured Reservoirs
Authors: Thanh Hung Vo , Lee Kang-Kun 
Published: September 2021

Abstract
Basement formation is known as the unique reservoir in the world. The fractured basement reservoir was contributed a large amount of oil and gas for Vietnam petroleum industry. However, the geological modelling and optimization of oil production is still a challenge for fractured basement reservoirs. Thus, this study aims to introduce the efficient workflow construction reservoir models for proposing the field development plan in a fractured crystalline reservoir. First, the Halo method was adapted for building the petrophysical model. Then, Drill stem history matching is conducted for adjusting the simulation results and pressure measurement. Next, the history-matched models are used to conduct the simulation scenarios to predict future reservoir performance. The possible potential design has four producers and three injectors in the fracture reservoir system. The field prediction results indicate that this scenario increases approximately 8 % oil recovery factor compared to the natural depletion production. This finding suggests that a suitable field development plan is necessary to improve sweep efficiency in the fractured oil formation. The critical contribution of this research is the proposed modelling and simulation with less data for the field development plan in fractured crystalline reservoir. This research's modelling and simulation findings provide a new solution for optimizing oil production that can be applied in Vietnam and other reservoirs in the world.
Expression of the Laminin-5γ2 Chain Is Associated With Acquisition of Malignant Traits in Ovarian Serous and Mucinous Tumors.
Authors: Tajika Yosuke , Imura Johji , Noguchi Akira , Orita Megumi , Nakajima Yuki , Minamisaka Takashi , Takagi Kohji , Tanaka Shinichi , Shima Tomoko , Nakashima Akitoshi 
Published: September 2021

Abstract
BackgroundOvarian tumors are predominantly of epithelial origin and are currently divided into three groups: Adenoma, borderline tumor, and adenocarcinoma by the presence or absence of invasion and cellular atypia. However, it is difficult to assess invasion, so a more objective biomarker would be desirable. Laminin-5 (Lam5) is a protein that constitutes the extracellular matrix of the basement membrane, and it is composed of three short-chain subunits. One of them, the Lam5γ2 chain (Lam5γ2), has been reported to be expressed in some malignant tumors and is suggested to be related to tumor cell invasion. Against this background, we investigated immunohistologically whether the Lam5γ2 would be useful as a marker to predict invasion in ovarian serous and mucinous tumors.MethodsImmunohistochemistry for Lam5γ2 was performed on a total of 80 cases of serous and mucinous tumor adenomas, borderline tumors, and adenocarcinomas, and the differences in the localization of Lam5γ2 expression were observed.ResultsThe basement membrane expression of Lam5γ2 tended to be preserved or had disappeared in half of the adenomas and borderline serous tumors. In all cases of adenocarcinoma, the expression on the basement membrane had disappeared. The frequency of expression in tumor cells increased in the order of adenoma, borderline tumor, adenocarcinoma. In particular, in most adenocarcinoma cases a cytoplasmic expression was observed. The same tendency was noted in mucinous tumors, and the basement membrane expression tended to disappear in the order of adenoma, borderline tumor and adenocarcinoma. Many cases of adenocarcinoma were observed among the tumor cells. In adenocarcinoma cases of both types of tumor, many tumor cells showed prominent cytoplasmic expression particularly in the microinvasive foci and in the invasive front.ConclusionsThe disappearance of Lam5γ2 from the basement membrane and its aberrant expression in serous and mucinous tumor cells may serve as a phenotype for invasiveness.