Multiple Tools Research Articles

Serine Protease 27, a Prognostic Biomarker in Pan-cancer and Associated with the Aggressive Progression of Breast Cancer.

To create effective medicines, researchers must first identify the common or unique genes that drive oncogenic processes in human cancers. Serine protease 27 (PRSS27) has been recently defined as a possible driver gene in esophageal squamous cell carcinoma. However, no thorough pan-cancer study has been performed to date, including breast cancer. Using the TCGA (The Cancer Genome Atlas), the GEO (Gene Expression Omnibus) dataset, and multiple bioinformatic tools, we investigated the function of PRSS27 in 33 tumor types. In addition, prognosis analysis of PRSS27 in breast cancer was carried out, as well as in vitro experiments to verify its role as an oncogene. We first explored the expression of PRSS27 in over 10 tumors and then we looked into PRSS27 genomic mutations. We discovered that PRSS27 has prognostic significance in breast cancer and other cancers' survival, and we developed a breast cancer prognostic prediction model by combining a defined set of clinical factors. Besides, we confirmed PRSS27 as an oncogene in breast cancer using some primary in vitro experiments. Our pan-cancer survey has comprehensively reviewed the oncogenic function of PRSS27 in various human malignancies, suggesting that it may be a promising prognostic biomarker and tumor therapeutic target in breast cancer.

Predictive Power of Dependence and Clinical-Social Fragility Index and Risk of Fall in Hospitalized Adult Patients: A Case-Control Study.

Accidental falls are among the leading hospitals' adverse events, with incidence ranging from 2 to 20 events per 1.000 days/patients. The objective of this study is to assess the relationship between in-hospital falls and the score of 3 DEPendence and Clinical-Social Fragility indexes. A monocentric case-control study was conducted by retrieving data of in-hospital patients from the electronic health records. Significant differences between the mean scores at the hospital admission and discharge were found. The BRASS scale mean (SD) values at the admission and at the discharge were also significantly higher in cases of in-hospital falls: at the admission 10.2 (±7.7) in cases versus 7.0 (±8.0) in controls ( P = 0.003); at the discharge 10.0 (±6.4) versus 6.7 (±7.5) ( P = 0.001). Barthel index mean (SD) scores also presented statistically significant differences: at the admission 60.3 (±40.6) in cases versus 76.0 (±34.8) in controls ( P = 0.003); at discharge 51.3 (±34.9) versus 73.3 (±35.2) ( P = 0.000).Odds ratios were as follows: for Barthel index 2.37 (95% CI, 1.28-4.39; P = 0.003); for Index of Caring Complexity 1.45 (95% CI, 0.72-2.91, P = 0. 255); for BRASS index 1.95 (95% CI, 1.03-3.70, P = 0.026). With BRASS index, the area under the curve was 0.667 (95% CI, 0.595-0.740), thus indicating a moderate predictive power of the scale. The use of only Conley scale-despite its sensitivity and specificity-is not enough to fully address this need because of the multiple and heterogeneous factors that predispose to in-hospital falls. Therefore, the combination of multiple tools should be recommended.

Comparison of the performance of multiple whole-genome sequence-based tools for the identification of Bacillus cereus sensu stricto biovar Thuringiensis.

The Bacillus cereus sensu stricto (s.s.) species comprises strains of biovar Thuringiensis (Bt) known for their bioinsecticidal activity, as well as strains with foodborne pathogenic potential. Bt strains are identified (i) based on the production of insecticidal crystal proteins, also known as Bt toxins, or (ii) based on the presence of cry, cyt, and vip genes, which encode Bt toxins. Multiple bioinformatics tools have been developed for the detection of crystal protein-encoding genes based on whole-genome sequencing (WGS) data. However, the performance of these tools is yet to be evaluated using phenotypic data. Thus, the goal of this study was to assess the performance of four bioinformatics tools for the detection of crystal protein-encoding genes. The accuracy of sequence-based identification of Bt was determined in reference to phenotypic microscope-based screening for the production of crystal proteins. A total of 58 diverse B. cereus sensu lato strains isolated from clinical, food, environmental, and commercial biopesticide products underwent WGS. Isolates were examined for crystal protein production using phase contrast microscopy. Crystal protein-encoding genes were detected using BtToxin_Digger, BTyper3, IDOPS (identification of pesticidal sequences), and Cry_processor. Out of 58 isolates, the phenotypic production of crystal proteins was confirmed for 18 isolates. Specificity and sensitivity of Bt identification based on sequences were 0.85 and 0.94 for BtToxin_Digger, 0.97 and 0.89 for BTyper3, 0.95 and 0.94 for IDOPS, and 0.88 and 1.00 for Cry_processor, respectively. Cry_processor predicted crystal protein production with the highest specificity, and BtToxin_Digger and IDOPS predicted crystal protein production with the highest sensitivity. Three out of four tested bioinformatics tools performed well overall, with IDOPS achieving high sensitivity and specificity (>0.90).IMPORTANCEStrains of Bacillus cereus sensu stricto (s.s.) biovar Thuringiensis (Bt) are used as organic biopesticides. Bt is differentiated from the foodborne pathogen Bacillus cereus s.s. by the production of insecticidal crystal proteins. Thus, reliable genomic identification of biovar Thuringiensis is necessary to ensure food safety and facilitate risk assessment. This study assessed the accuracy of whole-genome sequencing (WGS)-based identification of Bt compared to phenotypic microscopy-based screening for crystal protein production. Multiple bioinformatics tools were compared to assess their performance in predicting crystal protein production. Among them, identification of pesticidal sequences performed best overall at WGS-based Bt identification.

66 Effect of copper oxide wire particles on parasitism and growth in Katahdin lambs divergently selected for fecal egg count estimated breeding value

Abstract Internal parasites are one of the greatest threats to small ruminant production across the United States and parasitic resistance to anthelmintics continues to increase. Genetic selection and copper oxide wire particles (COWP) are two tools that could help reduce effects of parasites in small ruminants. The objective of this project was to determine the effects and interactions of COWP and genetic selection based on fecal egg count (FEC) estimated breeding value (EBV) on gastrointestinal nematode (GIN) infection and performance in naturally infected Katahdin lambs. Spring-born Katahdin ram lambs (n = 52) selected for extremely high FEC EBV (HighFEC, PFEC EBV = +100%) or low FEC EBV (LowFEC, PFEC EBV = -81%) were managed on a fescue-based pasture at the Southwest Virginia Agricultural Research and Extension Center (Glade Spring, VA). At weaning (June 29), lambs were dewormed with a three-combination treatment and rested for 21 d. At the start of the project (July 18), a random subset of lambs (HighFEC, n = 11; LowFEC, n = 15) were given a 2 g copper oxide wire particle bolus, while an equal number of remaining lambs were managed as controls without a copper bolus. All lambs were managed as one contemporary group. Fecal egg counts, FAMACHA scores, body weights, and packed cell volume (PCV) were measured bi-weekly for 10 weeks. Statistical analysis was performed using PROC Mixed Procedure of SAS (SAS Institute, Cary, NC) and FEC data were log transformed for normality. There were no effects of COWP treatment on FEC (P = 0.18). However, LowFEC-selected lambs had less FEC than HighFEC-selected lambs (230 vs. 565 eggs/g, respectively; P < 0.01). There was no interaction of COWP treatment and FEC genotype (P = 0.37). Copper oxide wire particle treatment had no effect on lamb body weight (P = 0.21), PCV (P = 0.69), FAMACHA score (P = 0.41), or overall ADG (P = 0.12). Lamb FEC genotype did not affect FAMACHA score or overall ADG (P = 0.10 and P = 0.22, respectively). LowFEC-selected lambs had lighter body weights (27.7 vs. 30.6 kg, respectively) and PCV (29.2% vs. 30.4%, respectively) than the HighFEC-selected lambs (P < 0.05). None of the 52 lambs met the requirement for deworming (FAMACHA ≥ 3) during the study. These results indicate that lamb FEC genotype may have a greater effect on parasitism than COWP treatment when given once during the post-weaning period. Even so, multiple tools should be considered, in addition to selection, for an integrated parasite management plan.

Guideline directed medical therapy induced nephrotoxicity in HFrEF patients; an insight to its mechanism

Guideline Directed Medical Therapy (GDMT) has been the standard pharmacotherapy for the treatment of Heart Failure patients with reduced Ejection Fraction (HFrEF) recommended by the European Society of Cardiology (ESC). However, patients on GDMT are likely to possess nephrotoxicity as an adverse effect. We utilized multiple system biology tools like ADVER-Pred, gene enrichment analysis, molecular docking, molecular dynamic simulations, and MMPBSA analysis to predict a possible molecular mechanism of how selected combinations of GDMT may cause nephrotoxicity. As per the ACC/AHA/ESC guidelines, we categorized the drugs as category 1 including β-blockers (BB), angiotensin receptor blockers (ARB), and sodium-glucose cotransporter-2 inhibitors (SGLT2I), category 2 includes BB’s, SGLT2I, and angiotensin receptor-neprilysin inhibitors (ARNI), and category 3 includes BB’s, SGLT2I, and angiotensin-converting enzyme (ACE) inhibitors. Enrichment analysis predicted category 2 drugs to possess the highest number of proteins to be involved in the development of nephrotoxicity i.e. 79.41%. The targets HBA1, CBR1, ATG5, and SLC6A3 were the top hub genes with an edge count of 7 followed by GPX1 with an edge count of 6. Molecular docking studies revealed candesartan-SLC6A3 to possess the highest binding affinity of −10.2 kcal/mol. In addition, simulation studies displayed empagliflozin-CBR1 to possess the highest stability followed by candesartan-ATG5. A combination of β-blockers, ARBs, and SGLT2I are predicted to likely possess nephrotoxicity which may be due to the modulation of HBA1, CBR1, ATG5, and GPX1. In conclusion, candesartan and empagliflozin are most likely to cause nephrotoxicity via the modulation of HBA1, CBR1, ATG5, and GPX1. Communicated by Ramaswamy H. Sarma

4 Utilizing SmartFeed Pro and SuperSmart Feeders for applied beef cattle research

Abstract Designing research for applied beef cattle production systems has always presented challenges for Land Grant University and USDA Scientist. Specifically, creating study designs that have enough replication for statistical inference has often prompted scientists to use designs that do not closely replicate actual production systems. Past research has often used multiple replications (pens/paddocks/pastures) that utilize replication (group averages; 4 – 8 animals) means as the experimental unit. While effective in measuring average treatment responses, these types of study designs do little to describe the actual individual animal behavior and performance in a more practical production environments. Approaches to increasing statistical observations in actual production environments will be discussed in this presentation. Embracing new technologies such as GPS, activity monitors, EID tags, and feed intake monitors (C-Lock Inc, GrowSafe) combined with multiple regression modeling tools can aid in designing and publishing beef cattle production research in actual beef production environments. Research at Montana State University has utilized SmartFeed Pro and SuperSmart Feeders for strategic supplementation research on extensive rangelands and dry-land pastures for the past seven years. Results of these studies have evaluated self-fed (salt-limited; loose, pelleted, and baked molasses blocks) as well as hand-fed supplements where daily intakes are limited by the locking gate on the feeder. This presentation will summarize these studies with a focus on research designs that were successful and/or unsuccessful in respect to characterizing beef cattle performance in production settings. Our goal will be to assist the audience in the application of feed intake technology in designing future applied beef cattle research.

Assessing habitat connectivity of rare species to inform urban conservation planning.

Urbanization is commonly associated with biodiversity loss and habitat fragmentation. However, urban environments often have greenspaces that can support wildlife populations, including rare species. The challenge for conservation planners working in these systems is identifying priority habitats and corridors for protection before they are lost. In a rapidly changing urban environment, this requires prompt decisions informed by accurate spatial information. Here, we combine several approaches to map habitat and assess connectivity for a diverse set of rare species in seven urban study areas across southern Michigan, USA. We incorporated multiple connectivity tools for a comprehensive appraisal of species-habitat patterns across these urban landscapes. We observed distinct differences in connectivity by taxonomic group and site. The three turtle species (Blanding's, Eastern Box, and Spotted) consistently had more habitat predicted to be suitable per site than other evaluated species. This is promising for this at-risk taxonomic group and allows conservation efforts to focus on mitigating threats such as road mortality. Grassland and prairie-associated species (American Bumble Bee, Black and Gold Bumble Bee, and Henslow's Sparrow) had the least amount of habitat on a site-by-site basis. Kalamazoo and the northern Detroit sites had the highest levels of multi-species connectivity across the entire study area based on the least cost paths. These connectivity results have direct applications in urban planning. Kalamazoo, one of the focal urban regions, has implemented a Natural Features Protection (NFP) plan to bolster natural area protections within the city. We compared our connectivity results to the NFP area and show where this plan will have an immediate positive impact and additional areas for potential consideration in future expansions of the protection network. Our results show that conservation opportunities exist within each of the assessed urban areas for maintaining rare species, a key benefit of this multi-species and multi-site approach.

A novel mutation in GTPBP3 causes combined oxidative phosphorylation deficiency 23 by affecting pre-mRNA splicing

BackgroundCombined Oxidative Phosphorylation Deficiency 23 (COXPD23) is a rare mitochondrial disease caused by mutations in the GTPBP3 gene. The rare incidence of the disease and the high clinical heterogeneity pose challenges in making a precise diagnosis. Investigations into the rare COXPD23 patients are of pathophysiological and etiological value. In this study, we investigated the genotype-phenotype relationship in a COXPD23 patient from a Manchu family, with GTPBP3 mutations. MethodsRoutine physical examinations, laboratory assays and imaging analyses were performed. The metabolic profiles of amino acids in blood, acylcarnitine in blood and organic acids in urine were used to determine the presence of inherited metabolic diseases. Genetic variations in the family were investigated using whole-exome sequencing and Sanger sequencing. Splicing disruption by a mutation was predicted and verified using a minigene assay. ResultsThe patient presented with severe lactic acidosis, neurological symptoms, multiple symmetrical lesions in the brain and serious mitochondrial energy metabolism disturbances. The c.689A > C (p.Q230P) and c.809-1_809delinsA compound heterozygous mutations were detected in GTPBP3. The novel c.809-1_809delinsA mutation was located at the splicing site of exon 7 and intron 6 and multiple tools predicted that it would disrupt the normal splicing. The minigene assay proved that the novel mutation resulted in two aberrant transcripts that created premature termination codons. ConclusionsThe clinical manifestations, brain imaging change, mitochondrial metabolism disturbances and the detection and validation of the GTPBP3 mutations expand the profile of COXPD23 and the pathogenic mutation spectrum. Our study improves the understanding of the pathophysiology and etiology of COXPD23.

Epitope Identification of an mGlu5 Receptor Nanobody Using Physics-Based Molecular Modeling and Deep Learning Techniques.

The world has witnessed a revolution in therapeutics with the development of biological medicines such as antibodies and antibody fragments, notably nanobodies. These nanobodies possess unique characteristics including high specificity and modulatory activity, making them promising candidates for therapeutic applications. Identifying their binding mode is essential for their development. Experimental structural techniques are effective to get such information, but they are expensive and time-consuming. Here, we propose a computational approach, aiming to identify the epitope of a nanobody that acts as an agonist and a positive allosteric modulator at the rat metabotropic glutamate receptor 5. We employed multiple structure modeling tools, including various artificial intelligence algorithms for epitope mapping. The computationally identified epitope was experimentally validated, confirming the success of our approach. Additional dynamics studies provided further insights on the modulatory activity of the nanobody. The employed methodologies and approaches initiate a discussion on the efficacy of diverse techniques for epitope mapping and later nanobody engineering.

Investigation of a novel TBC1D24 variation causing autosomal dominant non-syndromic hearing loss.

Hearing loss is considered one of the most common sensory neurological defects, with approximately 60% of cases attributed to genetic factors. Human pathogenic variants in the TBC1D24 gene are associated with various clinical phenotypes, including dominant nonsyndromic hearing loss DFNA65, characterized by progressive hearing loss after the development of language. This study provides an in-depth analysis of the causative gene and mutations in a family with hereditary deafness. We recruited a three-generation family with autosomal dominant nonsyndromic hearing loss (ADNSHL) and conducted detailed medical histories and relevant examinations. Next-generation sequencing (NGS) was used to identify genetic variants in the proband, which were then validated using Sanger sequencing. Multiple computational software tools were employed to predict the impact of the variant on the function and structure of the TBC1D24 protein. A series of bioinformatics tools were applied to determine the conservation characteristics of the sequence, establish a three-dimensional structural model, and investigate changes in molecular dynamics. A detailed genotype and phenotype analysis were carried out. The family exhibited autosomal dominant, progressive, postlingual, and nonsyndromic sensorineural hearing loss. A novel heterozygous variant, c.1459C>T (p.His487Tyr), in the TBC1D24 gene was identified and confirmed to be associated with the hearing loss phenotype in this family. Conservation analysis revealed high conservation of the amino acid affected by this variant across different species. The mutant protein showed alterations in thermodynamic stability, elasticity, and conformational dynamics. Molecular dynamics simulations indicated changes in RMSD, RMSF, Rg, and SASA of the mutant structure. We computed the onset age of non-syndromic hearing loss associated with mutations in the TBC1D24 gene and identified variations in the hearing progression time and annual threshold deterioration across different frequencies. The identification of a new variant associated with rare autosomal dominant nonsyndromic hereditary hearing loss in this family broadens the range of mutations in the TBC1D24 gene. This variant has the potential to influence the interaction between the TLDc domain and TBC domain, thereby affecting the protein's biological function.

Measures for Persons with Spinal Cord Injury to Monitor Their Transitions in Care, Health, Function, and Quality of Life Experiences and Needs: A Protocol for Co-Developing a Self-Evaluation Tool.

Evaluating the experiences of persons with spinal cord injury (PwSCI) regarding their transitions in care and changes in health, function, and quality of life is complex, fragmented, and involves multiple tools and measures. A staged protocol was implemented with PwSCI and relevant expert stakeholders initially exploring and selecting existing measures or tools through a modified Delphi process, followed by choosing one of two options. The options were to either support the use of the 10 selected tools from the Delphi method or to co-develop one unique condensed tool with relevant measures to evaluate all four domains. The stakeholders chose to co-develop one tool to be used by persons with SCI to monitor their transition experiences across settings and care providers. This includes any issues with care or support they needed to address at the time of discharge from acute care or rehabilitation and in the community at 3, 6, and 12 months or longer post-discharge. Once developed, the tool was made available online for the final stage of the protocol, which proposes that the tool be reliability tested prior to its launch, followed by validation testing by PwSCI.

Whole-exome sequencing identifies ADGB as a novel causative gene for male infertility in humans: from motility to fertilization.

In male mice, adgb-knockout has been reported to cause male infertility with spermatogenesis defects involving flagella and acrosome. However, this remains unclear for humans. Sequencing studies were conducted in a research hospital on samples from three unrelated infertile men with severe asthenoteratozoospermia from Han Chinese families. Data were collected through rigorous in silico analysis. Sanger sequencing were performed to identify pathogenic mutations. Sperm cells from patients were characterized using electron microscopy and used to verify the pathogenicity of the genetic factors through functional assays. Intracytoplasmic sperm injections (ICSI) assays were performed in ADGB-affected males. Herein, in a cohort of 105 Han Chinese men with idiopathic asthenoteratozoospermia, we reported the identification of bi-allelic deleterious variants of ADGB in three infertile men from unrelated families using whole-exome sequencing. We found one homozygous frameshift ADGB variant (NM_024694.4: c.2801_2802del:p.K934Rfs*33), one homozygous missense ADGB variant (NM_024694.4: c.C3167T:p.T1056I), and one compound heterozygous ADGB variant (NM_024694.4: c.C3167T:p.T1056I; c.C3197T:p.A1066V). These variants were rare in general population and were predicted to be damaging by multiple bioinformatics tools. Further, the spermatozoa from patients harboring ADGB variants showed multiple acrosome and flagellum malformations under light and electron microscopy. Functional assays revealed the structural defects associated with dysregulation of ADGB and multiple spermatogenesis proteins. Notably, the fertilization success via ICSI treatment in all three patients, as well as the normal expression of PLCζ but CaM deficiency in the spermatozoa, suggesting that ICSI other than in vitro fertilization (IVF) is an optimal treatment for ADGB-deficient patients. Our findings provide new information for the molecular diagnosis of asthenoteratozoospermia and valuable reference for personalized genetic counselling and clinical treatment for these patients. The underlying risk of IVF failure behind sperm defects was highlighted.

Benchmarking informatics approaches for virus discovery: caution is needed when combining in silico identification methods.

The identification of viruses from environmental metagenomes using informatics tools has offered critical insights in microbial ecology. However, it remains difficult for researchers to know which tools optimize viral recovery for their specific study. In an attempt to recover more viruses, studies are increasingly combining the outputs from multiple tools without validating this approach. After benchmarking combinations of six viral identification tools against mock metagenomes and environmental samples, we found that these tools should only be combined cautiously. Two to four tool combinations maximized viral recovery and minimized non-viral contamination compared with either the single-tool or the five- to six-tool ones. By providing a rigorous overview of the behavior of in silico viral identification strategies and a pipeline to replicate our process, our findings guide the use of existing viral identification tools and offer a blueprint for feature engineering of new tools that will lead to higher-confidence viral discovery in microbiome studies.

Factors of BPD Deposit Interest Rate, Government Bank Deposit Interest Rate, Inflation Rate, Economic Growth (GDP) and Money Supply to the Rupiah Exchange Rate per US dollar in Indonesia for the Period 2004 - 2021

The study aims to analyze the effect of the BPD Deposit Interest Rate Factor, Government Bank Deposit Interest Rate, Inflation Rate, economic growth, and money supply affecting the exchange rate of the rupiah per US dollar in 2004-2021 partially and simultaneously. The research method uses secondary data in the form of panel data and cross section for 18 years (quarterly data on 26 provinces in Indonesia). Literature survey research from BI, BPD, and BPS Center. Quantitative analysis method using multiple linear regression analysis tools. The results showed that (1) partially, the interest rate factor of Government Bank deposits, the money supply has a positive but insignificant effect on the exchange rate of the rupiah per US dollar. Regional Development Bank deposit interest rates, inflation rates, and economic growth have a negative but significant effect on the exchange rate of the rupiah per US dollar; and (2) simultaneously, the factors of interest rates on deposits of BPD, interest rates on deposits of Government Banks, inflation rates, economic growth, money supply have a significant effect on the exchange rate of rupiah per US dollar. An increase in interest rates on deposits of Government Banks and money supply, a decrease in interest rates on deposits of BPD, inflation rates, and economic growth will increase the exchange rate of rupiah (depreciated).

New reference genomes to distinguish the sympatric malaria parasites, Plasmodium ovale curtisi and Plasmodium ovale wallikeri

Despite Plasmodium ovale curtisi (Poc) and wallikeri (Pow) being important human-infecting malaria parasites that are widespread across Africa and Asia, little is known about their genome diversity. Morphologically identical, Poc and Pow are indistinguishable and commonly misidentified. Recent rises in the incidence of Poc/Pow infections have renewed efforts to address fundamental knowledge gaps in their biology, and to develop diagnostic tools to understand their epidemiological dynamics and malaria burden. A major roadblock has been the incompleteness of available reference assemblies (PocGH01, PowCR01; ~ 33.5 Mbp). Here, we applied multiple sequencing platforms and advanced bioinformatics tools to generate new reference genomes, Poc221 (South Sudan; 36.0 Mbp) and Pow222 (Nigeria; 34.3 Mbp), with improved nuclear genome contiguity (> 4.2 Mbp), annotation and completeness (> 99% Plasmodium spp., single copy orthologs). Subsequent sequencing of 6 Poc and 15 Pow isolates from Africa revealed a total of 22,517 and 43,855 high-quality core genome SNPs, respectively. Genome-wide levels of nucleotide diversity were determined to be 2.98 × 10–4 (Poc) and 3.43 × 10–4 (Pow), comparable to estimates for other Plasmodium species. Overall, the new reference genomes provide a robust foundation for dissecting the biology of Poc/Pow, their population structure and evolution, and will contribute to uncovering the recombination barrier separating these species.

Gastroesophageal reflux disease with 6 neurodegenerative and psychiatric disorders: Genetic correlations, causality, and potential molecular mechanisms

The comorbidities between gastroesophageal reflux disease (GERD) and various neurodegenerative and psychiatric disorders have been widely reported. However, the genetic correlations, causal relationships, and underlying mechanisms linking GERD to these disorders remain largely unknown. Here, we conducted a bidirectional Mendelian randomization (MR) analysis to determine the causality between GERD and 6 neurodegenerative and psychiatric disorders. Sensitivity analyses and multivariable MR were performed to test the robustness of our findings. Linkage disequilibrium score regression was used to assess the genetic correlation between these diseases as affected by heredity. Multiple bioinformatics tools combining two machine learning algorithms were applied to further investigate the potential mechanisms underlying these diseases. We found that genetically predicted GERD significantly increased the risk of Alzheimer's disease, major depressive disorder, and anxiety disorders. There might be a bidirectional relationship between GERD and insomnia. GERD has varying degrees of genetic correlations with AD, ALS, anxiety disorders, insomnia, and depressive disorder. Bioinformatics analyses revealed the hub shared genes and the common pathways between GERD and 6 neurodegenerative and psychiatric disorders. Our findings demonstrated the complex nature of the genetic architecture across these diseases and clarified their causality, highlighting that treatments for the cure or remission of GERD may serve as potential strategies for preventing and managing neurodegenerative and psychiatric disorders.

Gut microbiome-metabolome interactions predict host condition

BackgroundThe effect of microbes on their human host is often mediated through changes in metabolite concentrations. As such, multiple tools have been proposed to predict metabolite concentrations from microbial taxa frequencies. Such tools typically fail to capture the dependence of the microbiome-metabolite relation on the environment.ResultsWe propose to treat the microbiome-metabolome relation as the equilibrium of a complex interaction and to relate the host condition to a latent representation of the interaction between the log concentration of the metabolome and the log frequencies of the microbiome. We develop LOCATE (Latent variables Of miCrobiome And meTabolites rElations), a machine learning tool to predict the metabolite concentration from the microbiome composition and produce a latent representation of the interaction. This representation is then used to predict the host condition. LOCATE’s accuracy in predicting the metabolome is higher than all current predictors. The metabolite concentration prediction accuracy significantly decreases cross datasets, and cross conditions, especially in 16S data. LOCATE’s latent representation predicts the host condition better than either the microbiome or the metabolome. This representation is strongly correlated with host demographics. A significant improvement in accuracy (0.793 vs. 0.724 average accuracy) is obtained even with a small number of metabolite samples (∼50\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$\\sim 50$$\\end{document}).ConclusionThese results suggest that a latent representation of the microbiome-metabolome interaction leads to a better association with the host condition than any of the two separated or the simple combination of the two.65xPsFnnFGsq3M5WjZwrxcVideo

How Shifting Focus from Register to Data Functionality Can Enhance Register and Bus Management

Bus and register management is one of the crucial aspects of application-specific integrated circuit-, system-on-chip-, or field-programmable gate array-based designs. The problems related to it are well known, and multiple tools or approaches are already trying to solve or mitigate them. However, all available solutions share the same register-centric paradigm. A user defines registers and then manually lays out the data into the registers. Such an approach has its limitations. A description does not contain information on data spanning multiple registers or data forming a broader context, for example, procedure arguments. It also does not contain information on the purpose of the data. As a result, the generated access code is low-level and usually needs an extra wrapper, which leaves room for potential human mistakes. For instance, it is the user’s responsibility to guarantee proper access order to registers or to provide an atomic change of data wider than a single register width. This article proposes a new approach, the functionality-centric approach. In the functionality-centric approach, the user defines the data with the type of their functionality. The registers and bus hierarchy are later implicitly inferred. By defining the functionality of the data placed in the registers, it is possible to generate more access code, increase code robustness, improve system design readability, and shorten the implementation process.

Performance is Reviewed from Motivation, Competency, Discipline and Organizational Culture of UPT PLDPI Employees of the Surakarta City Education Service

This research uses a quantitative descriptive approach. In this quantitative descriptive research, the author focuses research on Motivation, Ability and Work Discipline which influence the performance of UPT PLDPI Employees at the Surakarta City Education Service. This research was used to see the influence of motivation, ability and work discipline on the performance of UPT PLDPI employees at the Surakarta City Education Service by collecting data using questionnaires, observation and documentation. Research Location UPT PLDPI Office Surakarta City Education Service Jl, Agung Timur 6A Ngemplak Sutan, Mojosongo Jebres Surakarta. In conducting this research, the time required is 6 months from March – September 2023, starting from observation to producing data results and research conclusions. The population in this study were employees of the UPT PLDPI Surakarta City Education Service, totaling 41 employees. The samples taken in this research were 41 employees of the UPT PLDPI Surakarta City Education Service. Questionnaire collection results using multiple linear regression analysis tools with the help of the SPSS 23 application.Based on the results of the analysis that has been carried out, thenMotivation, Competence, Discipline, Organizational culture influence employee performance at UPT PLDPI Surakarta City Education Service.

Measuring Employee Performance Post Pandemi Covid-19 View From Motivation, Competence, Discipline and Work Environment at Palang Merah Indonesia (PMI) Klaten Regency

This study used a quantitative descriptive approach. The author chooses to use this quantitative descriptive method to determine the amount of influence and significance between the variables of competence, motivation, work discipline, culture and work environment on employee performance. The research was conducted at the Indonesian Red Cross Office (PMI) Klaten Regency which is located at Jalan Veteran No. 80 North Klaten, Klaten - Central Java 57431, Indonesia, the research time was carried out for 6 (six) months. The population in this study is all PMI employees of Klaten Regency totaling 60 people. The sample taken in this study was as many as 60 respondents The sampling technique used in this study was a census technique. The census method is a sampling technique when all members of the population are used as samples. After getting answers from respondents, the data is then processed using multiple linear regression analysis tools with the help of SPSS 23 software. Based on the results of the discussion above, the following conclusions can be drawn that have a significant effect on the performance of PMI Employees of Klaten Regency after the Covid-19 Pandemic. However, it did not have a significant effect on the performance of PMI Employees of Klaten Regency after the Covid-19 Pandemic