bluuebunny/crossref_metadata_2025_split huggingface dataset:
Machine learning in Huntington's disease: exploring the Enroll-HD dataset for prognosis &amp; driving capability prediction
Authors: Ouwerkerk Jasper , Feleus Stephanie , Zwaan Kasper van der , Li Yunlei , Roos Marco , Roon-Mom Willeke van , de Bot Susanne , Wolstencroft Katherine , Mina Eleni 
Published: March 2023

Abstract
Background: In biomedicine, machine learning (ML) has proven beneficial for the prognosis and diagnosis of different diseases, including cancer and neurodegenerative disorders. For rare diseases, however, the requirement for large datasets often prevents this approach. Huntington’s disease (HD) is a rare neurodegenerative disorder caused by a CAG repeat expansion in the coding region of the huntingtin gene. The world’s largest observational study for HD, Enroll-HD, describes over 21,000 participants. As such, Enroll-HD is amenable to ML methods. In this study, we pre-processed and imputed Enroll-HD with ML methods to maximise the inclusion of participants and variables. With this dataset we developed models to improve the prediction of the age at onset (AAO) and compared it to the well-established Langbehn formula. In addition, we used recurrent neural networks (RNNs) to demonstrate the utility of ML methods for longitudinal datasets, assessing driving capabilities by learning from previous participant assessments.
Results: Simple pre-processing imputed around 42% of missing values in Enroll-HD. Also, 167 variables were retained as a result of imputing with ML. We found that multiple ML models were able to outperform the Langbehn formula. The best ML model (light gradient boosting machine) improved the prognosis of AAO compared to the Langbehn formula by 9.2%, based on root mean squared error in the test set. In addition, our ML model provides more accurate prognosis for a wider CAG repeat range compared to the Langbehn formula. Driving capability was predicted with an accuracy of 85.2%. The resulting pre-processing workflow and code to train the ML models are available to be used for related HD predictions at: https://github.com/JasperO98/hdml/tree/main.
Conclusions: Our pre-processing workflow made it possible to resolve the missing values and include most participants and variables in Enroll-HD. We show the added value of a ML approach, which improved AAO predictions and allowed for the development of an advisory model that can assist clinicians and participants in estimating future driving capability.
Single Center Outcomes from Parenchymal-sparing Resections and Microwave Ablations for Neuroendocrine Tumor Liver Metastases
Authors: Lee Frances T. , Williams Jelani , Nordgren Rachel , Schwarz Jason L. , Setia Namrata , Roggin Kevin , Polite Blase , Rangrass Govind , Liao Chih-Yi , Millis J. Michael , Keutgen Xavier M. 
Published: March 2023

Abstract
Background: Surgical debulking of neuroendocrine tumor (NET) is used as a therapeutic approach for metastatic NETs in selected centers. Reported outcomes after parenchymal-sparing liver resections (PSR) in NET patients with high numbers of liver metastases are sparse.
Methods: NET patients that underwent surgical debulking from 2019 to 2021 were reviewed. Trends in perioperative liver function was examined, as well as symptom response, complications, and progression free survival.
Results: 1069 liver lesions (median=17) were debulked from 53 patients with a combination of PSR (45%) and ultrasound-guided microwave ablations (MWA) (55%). Post-operative transaminitis was proportional to the number of lesions debulked: Median POD1 AST was 681 IU/L for 1-15 lesions vs. 1396 IU/L for >15 lesions, p=0.01 (R2=0.271, p<0.001) and ALT was 596 IU/L vs 1149 IU/L, respectively, p=0.01 (R2=0.221, p<0.001). Thrombocytopenia occurred in 75% of patients and severity correlated with increasing number of lesions (median POD2 platelets 157 x 109/L for 1-15 lesions vs. 109 x 109/L for >15 lesions, p=0.04; R2=0.163, p=0.003). Synthetic liver function measured by postoperative INR (median POD1 INR 1.3 vs 1.4, p=0.21) and total bilirubin (median POD 2 TB 1.35 vs 0.95 mg/dL; p=0.67) did not differ according to number of lesions debulked. 13% of patients sustained a Clavien-Dindo grade 3/4 complication which was not associated with the number of lesions targeted. All patients with preoperative symptoms had improvement after surgery. Median time to recurrence was 10.9 months.
Conclusions: PSR with MWA for large numbers of NET liver metastases is safe and effective for symptom control and does not affect synthetic liver function. Transaminitis and thrombocytopenia are proportionate to the amount of liver lesions debulked.
Whole genome and RNA sequencing analyses for 254 Taiwanese hepatocellular carcinomas
Authors: Chang Ya-Sian , Tu Siang-Jyun , Chen Hong-Da , Chung Chin-Chun , Hsu Ming-Hon , Chou Yu-Pao , Lee Ya-Ting , Yen Ju-Chen , Jeng Long-Bin , Chang Jan-Gowth 
Published: March 2023

Abstract
Background
Comprehensive and integrative analysis of hepatocellular carcinoma (HCC) is important. In this study, we explored Taiwanese HCCs using multi-omics analyses.
Methods
We analyzed 254 HCCs by whole genome sequencing and total RNA sequencing, and then used bioinformatic tools to analyze genomic and transcriptomic alterations in coding and non-coding sequences to explore the clinical importance of each sequence.
Results
The frequencies of the five most commonly mutated cancer-related genes were TERT, TP53, CTNNB1, RB1, and ARID1A. Genetic alteration frequencies influenced the etiology of HCC; some alterations were also correlated with clinicopathological conditions. Many cancer-related genes had copy number alterations (CNAs) and structure variants (SVs) that changed according to etiology and exhibited potential associations with survival. We also identified several alterations in histone-related genes, HCC-related long non-coding RNAs, and non-coding driver genes that may contribute to the onset and progression of HCC. Transcriptomic analysis revealed that 229 differentially expressed and 148 novel alternative splicing (AS) genes, as well as the presence of fusion genes, were associated with patient survival. Moreover, somatic mutations, CNAs, and SVs were associated with immune checkpoint gene expression and tumor microenvironment. Finally, we identified relationships among AS, immune checkpoint gene expression and tumor microenvironment.
Conclusions
This study shows that genomic alterations are associated with survival, including DNA-based and RNA-based data. Moreover, genomic alterations and their associations with immune checkpoint genes and the tumor microenvironment may provide novel insights for the diagnosis and treatment of HCC.
Development of a machine learning-based prediction model for systemic inflammatory response syndrome after percutaneous nephrolithotomy and comparison with nomogram model
Authors: Zhang Tianwei , Zhu Ling , Wang Xinning , Zhang Xiaofei , Wang Zijie , Jiao Wei 
Published: March 2023

Abstract
The objective of this study was to develop and compare the performance of nomogram model and machine learning models for predicting the possibility of systemic inflammatory response syndrome (SIRS) following percutaneous nephrolithotomy (PCNL). We retrospectively reviewed the clinical data of 337 patients who received PCNL between May 2020 and June 2022. Eighty percent of the data were used as the training set, and the remaining data were used as the testing set. The nomogram and machine learning (ML) models were created using the training set and were validated using the testing set. Based on the areas under the receiver operating characteristic curve (AUC) and the calibration curve, we evaluated the predictive ability of the nomogram. The predictive performance of six machine learning models was determined by the AUC and accuracy. Multivariate logistic regression analysis revealed four independent risk factors associated with SIRS, including preoperative monocyte, serum fibrinogen, serum prealbumin, and preoperative SII. The above independent related factors were used as variables to construct the nomogram model. Among the six machine learning algorithms, the support vector machine (SVM) delivered the best performance with accuracy of 0.926, AUC of 0.952 [95% Confidence Interval (CI): 0.906–0.999], while the nomogram showed an AUC of 0.818. Compared with the nomogram model, the SVM model can provide more reliable prognostic information about the possibility of SIRS after PCNL, which can assist surgeons in clinical decision-making.
RETRACTED: Blood–Brain Barrier Disruption in Ischemic Stroke is associated with Perivenous-Enhanced Cortical Veins Detected by Contrast-Enhanced Black-Blood Magnetic Resonance Imaging.
Authors: Zhang Xiaoxia , Wang Tianle , Bai Yingnan , Li Zhiyu , Zhu Dan , Cheng Ailan , Li Yue-hua , Lu Qing 
Published: March 2023

Abstract

The authors have requested that this preprint be removed from Research Square.
Integrating Semantic Web into Context-Aware Mobile Application based on Cloud Computing
Authors: Lai Ting-Yan , Hsu I-Ching 
Published: March 2023

Abstract

The current context-aware mobile application approach lacks a standardized method for knowledge representation that can handle intelligence effects, such as automatic, dynamic, and intelligent support for mobile context-awareness applications. To tackle these intelligence issues, this research introduces the Semantic-aware Service into Cloud Computing Architecture (SSCCA) as a common scheme to enable intelligent context-aware mobile applications using a fundamental cloud service model. SSCCA combines Cloud Computing and Semantic Web research to facilitate the development of intelligent cloud computing applications. To validate the proposed approach, a Smart Context-aware Invoice Platform (SCIP), an intelligent cloud computing application built on SSCCA, is implemented to gather personal electronic invoices and offer context-aware mobile services on demand.
Mycelium material in interior design. Acceptance level amongst future users of new eco-aesthetics
Authors: Bonenberg Agata , Sydor Maciej , Doczekalska Beata , Cofta Grzegorz , Grygorowicz-Kosakowska Klaudia 
Published: March 2023

Abstract

Mycelium-based composites (MBCs) show great potential as a sustainable alternative to conventional biopolymers in the production of environmentally-friendly furniture and interior decor. While these innovative biocomposites have numerous ecological benefits, they pose a new challenge in aesthetics and consumer acceptance. Furniture made from mycelium and lignocellulosic substrates has a porous texture, uneven surface, and unpredictable coloring due to the natural growth patterns of mycelium. Although production methods can be improved and imperfections reduced, the inherent randomness of mycelium growth cannot be eliminated. These factors and the natural provenance of such materials can be a challenge in interior design. For these reasons, it is justified to measure the level of acceptance of such materials as objectively as possible. The article presents and justifies three complementary consumer tests suitable for MBC materials and product acceptance level measuring. The proposed set of consumer tests includes (1) an organoleptic evaluation of the material, using three senses simultaneously, (2) a product acceptance and desirability evaluation, and (3) comparative tests of products with the same function, dimensions, and shape, made of two different materials. The results of these tests are complementary and demonstrate to which extent products made of MBC are potentially acceptable to the public. All of these methods support current and future applications of MBC for manufacturing items where enhanced aesthetics are required.
The Self-Organized Criticality and Periodicity of Temporal Sequences of Earthquakes
Authors: Ida Yoshiaki 
Published: March 2023

Abstract

A new cellular automaton model has been developed to examine the nature of temporal sequences of earthquakes. The model takes the space dependence of strength on inhomogeneous faults into account and assumes that an earthquake produces a continuously connected area with uniform stress drop. In the model viscous slip is also introduced so that earthquakes may be realizable only when the applied stress accumulates faster than the viscous relaxation. The analysis reveals that the sequences of earthquakes commonly satisfy the power law relation between the intensity and frequency of earthquakes so that earthquakes may be in the state of self-organized criticality. On the other hand, periodicity appears in some sequences that consist of the groups of high seismic activity repeated between calm intervals at an almost constant period. Therefore, self-organized criticality and periodicity coexist in these sequences and the claim that earthquakes are unpredictable because of self-organized criticality may be inadequate.
Optimization of intracranial electrical stimulation to improve mood states
Authors: Cao Dan , Liu Qihong , Li Jin , Jiang Tianzi 
Published: March 2023

Abstract
Intracranial electrical stimulation (iES) is a promising tool for refractory mood disorders. Lack of efficacy in some iES studies raises questions about the optimal anatomical target, the timing of the stimulation, and the related neural mechanisms. Here, we combined iES with intracranial electroencephalography (iEEG) recordings to address the following questions: 1) Where to stimulate? We studied the effects of stimulation on brain regions in the emotional network and found that only orbitofrontal cortex (OFC) stimulation improved mood and induced related changes in neural activity. 2) When to stimulate? We tested the hypothesis that the effect of iES was state-dependent and investigated the brain state that facilitated the iES effect on mood states. We trained multivariate classifiers to discriminate neural activity that predicted mood states during natural mood fluctuations and then decoded the neural activity in later sessions when delivering stimulation. Stimulation suppressed the delta-theta power in the OFC if it was delivered when the brain was classified as being in a low mood state but had no effect when the brain was classified as being in a high mood state. 3) What are we modulating? OFC stimulation induced decreased delta-theta activity, increased gamma activity, and increased effective connectivity between areas in the emotional network. These findings suggest that the OFC is a promising new iES target and provided proof of concept for state-specific stimulation in mood improvement.
Pharmacogenomic Analysis of Medial Temporal Lobe Epilepsy with Hippocampal Sclerosis in Humans and Animal Models
Authors: Guo Jia , Liu Ruihan , Kong Yu , Xiao Xiangyu , Lv Shaomin , Lv Jiahua , Wang Xinyu , Yao Lei , Wang Xingchen , Li Xuebin , Wen Limin , Guo Yafeng , Shi Yaru , Tan Xinlu , Qiao Qicheng , Kong Qingxia 
Published: March 2023

Abstract
Background
Epilepsy is a neurological disorder caused by abnormal brain discharges. In recent years, genome-wide expression studies (GES) have been conducted using human patient samples and experimental models of epilepsy. Numerous molecular targets for epileptogenesis and treatment have been identified. However, there is still an urgent need to identify new biomarkers for epilepsy.
Methods
We performed a meta-analysis and convergence analysis of GES available from human samples and mouse and rat models to identify differentially expressed genes. Functional and pathway enrichment analysis of differentially expressed genes was performed using Sangerbox 3.0. Protein–protein interaction networks were mapped using STRING and subsequently visualized using Cytoscape. Disease gene–drug interactions were explored using the Comparative Toxicology Database and the Drug Gene Interaction Database.
Results
The ten most highly differentially expressed genes were, LRRTM1, STX1A, SNAP25, SYNPR, STXBP1, NRXN1, CPLX1, SYT4, SYT13 and GABRG2, which were supported by multi-lineage genomic evidence. A functional enrichment analysis identified several important classifications, including regulation of neuronal differentiation and regulation of vesicle-mediated transport. Potential druggable genes were also identified (e.g., LRRTM1, GABRG2, CYP4X1, CHGB and TMEM130).
Conclusions
We performed a meta-analysis and convergence analysis of GES from human samples and multiple animal models of epileptogenesis by integrating the results of several studies. We identified the top ten candidate genes and pathways for epileptogenesis. Among them, LRRTM1 and GABRG2 have been validated to have high druggable value. The other eight genes require further study to explore their potential as therapeutic targets in medial temporal lobe epilepsy with hippocampal sclerosis.
Comprehensive genetic screening of early-onset dementia patients in an Austrian Cohort-Suggesting new disease-contributing genes
Authors: Silvaieh Sara , König Theresa , Wurm Raphael , Parvizi Tandis , Berger-Sieczkowski Evelyn , Goeschl Stella , Hotzy Christoph , Wagner Matias , Berutti Riccardo , Sammler Esther , Stögmann Elisabeth , Zimprich Alexander 
Published: March 2023

Abstract
Early-onset dementia (EOD), with symptom onset before age 65, has a strong genetic burden. Due to genetic and clinical overlaps between different types of dementia, whole-exome sequencing (WES) has emerged as an appropriate screening method for diagnostic testing and novel gene-finding approaches. We performed WES and C9orf72 repeat testing in 60 well-defined Austrian EOD patients. Seven patients (12%) carried likely disease-causing variants in monogenic genes, PSEN1, MAPT, APP, and GRN. Five patients (8%) were APOE4 homozygote carriers. Definite and possible risk variants were detected in the genes TREM2, SORL1, ABCA7 and TBK1. In an explorative approach, we cross-checked rare gene variants in our cohort with a curated neurodegeneration candidate gene list and identified DCTN1, MAPK8IP3, LRRK2, VPS13C and BACE1 as promising candidate genes. Conclusively, 12 cases (20%) carried variants relevant to patient counseling, comparable to previously reported studies. Reduced penetrance, oligogenic inheritance and not yet identified high-risk genes might explain the high number of unresolved cases. To address this issue, we provide complete genetic and phenotypic information (uploaded to the European Genome-phenome Archive), enabling other researchers to cross-check variants. Thereby, we hope to increase the chance of independently finding the same gene/variant-hit in other well-defined EOD patient cohorts, thus confirming new genetic risk variants or variant combinations.
Facilitators and Barriers Faced by Women With Severe Mental Illness in Gaining Employment- a Qualitative Study From Rural India
Authors: Meera J , Sivakumar Thanapal , Shanivaram Reddy K , Kumar Devvarta , Chandra Prabha S 
Published: March 2023

Abstract

Background:Women with severe mental illness (SMI) in India endure various psychosocial issues besides the burden of mental illness. It becomes more challenging in rural areas due to difficulties accessing services and limited employment opportunities. Among various constraints, lack of employment opportunities is quite pressing as being employed helps women with SMI to have a better quality of life and a sense of independence. Given this, we tried to understand the facilitators and barriers women with SMI from rural areas face in gaining and continuing employment.
Methods: In-depth qualitative interviews were conducted to identify facilitators and barriers to employment opportunities for women with SMI in rural areas. Fifteen women with SMI receiving treatment from a community-based rehabilitation program run at an agrarian rural block in South India and other stakeholders, namely the caregivers of patients, a social worker, and a community program coordinator from a non-governmental organisation, were interviewed to understand the facilitators and barriers experienced by women with SMI in rural areas. Audio recordings of the interviews were transcribed, translated, and coded. Thematic analysis was used to identify emerging themes.
Results:Findings of the thematic analyses indicate that facilitators in getting employed are medication adherence, work experience, support from family and co-workers, and financial gain from employment. Barriers that restricted women with SMI from getting employed were lack of motivation, social exclusion, medication side-effects, default in previous loans (mainly taken for agriculture purposes), lack of proof of identity, stigma from the community, lack of empowerment, and a patriarchal mindset.
Conclusion:Employment is an essential part of recovery for women with SMI. The findings indicate the need to address systemic and personal barriers and promote work-related training and family support
Numerical approximations of one-point large deviations of stochastic differential equations with small noise
Authors: Hong Jialin , Jin Diancong , Sheng Derui 
Published: March 2023

Abstract
This paper studies the numerical approximation of the one-point large deviation of nonlinear stochastic differential equations (SDEs) with small noise via the stochastic θ-method. We first prove that the numerical method satisfies the one-point large deviations principle with a discrete rate function for sufficiently small step-size. It turns out that similar to the continuous case, the discrete rate function is also implicitly determined by the minimum of an action functional, which brings difficulty in the convergence analysis of the discrete rate functions. This is overcome by the error estimates between the numerical and original action functionals, the coerciveness of action functionals, and the continuity of the original rate function. As a result, we obtain that the convergence orders of the discrete rate function in the cases of multiplicative and additive noises are 1/2 and 1 respectively. Our results provide an effective approach to numerically approximating the asymptotical behavior of probabilities that exact solutions of SDEs with small noise deviate from their deterministic counterparts.
Large Deviations For Stochastic Volterra Equations With Reflection In Hölderian Norm
Authors: RANDRIANOMENJANAHARY R.A , RABEHERIMANANA T. J. 
Published: March 2023

Abstract
In this paper, we study the large deviations principle (LDP) of the Volterra process with reflection in Hölderian norm by the Azencott method. As an application, we obtain the large deviations principle (LDP) of a perturbed diffusion process driven by the Fractional Brownian Motion with Hurst parameter H ∈ (0, 1)
Bioproduction platform using a novel cane toad (Rhinella marina) N-methyltransferase for psychedelic-inspired drug discovery
Authors: Chen Xue , Li Jing , Yu Lisa , Dhananjaya D , Maule Francesca , Cook Sarah , Chang Limei , Gallant Jonathan , Press David , Bains Jaideep S , Raithatha Sheetal , Hagel Jillian , Facchini Peter 
Published: March 2023

Abstract
Psychedelic indolethylamines have emerged as potential medicines to treat several psychiatric pathologies. Natural sources of these compounds include ‘magic mushrooms’, plants used to prepare ahayuasca, and toads. Owing to the occurrence of indolethylamines such as N,N-dimethyltryptamine, toad skin and parotid gland preparations have a history of ceremonial use, yet their biosynthesis remains uncharacterized. We report the isolation of an indolethylamine N-methyltransferase (RmNMT) from cane toad (Rhinella marina). Unlike functionally similar mammalian and fungal enzymes, the efficiency and promiscuity of RmNMT made it suitable for the bioproduction of new-to-nature indolethylamine derivatives. N,N-Dimethylated indolethylamines showed reduced affinity and engagement at 5-HT1A and 5-HT2A receptors respectively, compared with primary amine equivalents. Despite reduced 5-HT2A receptor engagement of tertiary amines, only these molecules induced hallucinogenic behavior in mice underscoring the importance of metabolic stability. The discovery of RmNMT facilitated the establishment of a bioproduction platform for the isolation and pharmacological screening of novel indolethylamines.