Heifer conception rate to the first service (HCR1) is defined as the number of heifers that become pregnant to the first breeding service compared to the heifers bred. This study aimed to identify loci associated and gene sets enriched for HCR1 for heifers that were bred by artificial insemination (AI, n = 2829) or were embryo transfer (ET, n = 2086) recipients, by completing a genome-wide association analysis and gene set enrichment analysis using SNP data (GSEA-SNP). Three unique loci, containing four positional candidate genes, were associated (p < 1 × 10-5) with HCR1 for ET recipients, while the GSEA-SNP identified four gene sets (NES ≥ 3) and sixty-two leading edge genes (LEGs) enriched for HCR1. While no loci were associated with HCR1 bred by AI, one gene set and twelve LEGs were enriched (NES ≥ 3) for HCR1 with the GSEA-SNP. This included one gene (PKD2) shared between HCR1 AI and ET services. Identifying loci associated or enriched for HCR1 provides an opportunity to use them as genomic selection tools to facilitate the selection of cattle with higher reproductive efficiency, and to better understand embryonic loss.

Phylogenetic analysis has entered the genomics (multilocus) era. For less experienced researchers, conquering the large number of software programs required for a multilocus-based phylogenetic reconstruction can be somewhat daunting and time-consuming. PhyloSuite, a software with a user-friendly GUI, was designed to make this process more accessible by integrating multiple software programs needed for multilocus and single-gene phylogenies and further streamlining the whole process. In this protocol, we aim to explain how to conduct each step of the phylogenetic pipeline and tree-based analyses in PhyloSuite. We also present a new version of PhyloSuite (v1.2.3), wherein we fixed some bugs, made some optimizations, and introduced some new functions, including a number of tree-based analyses, such as signal-to-noise calculation, saturation analysis, spurious species identification, and etc. The step-by-step protocol includes background information (i.e., what the step does), reasons (i.e., why do the step), and operations (i.e., how to do it). This protocol will help researchers quick-start their way through the multilocus phylogenetic analysis, especially those interested in conducting organelle-based analyses.

BACKGROUND: Theory and correlational research indicate organizational leadership and climate are important for successful implementation of evidence-based practices (EBPs) in healthcare settings; however, experimental evidence is lacking. We addressed this gap using data from the WISDOM (Working to Implement and Sustain Digital Outcome Measures) hybrid type III effectiveness-implementation trial. Primary outcomes from WISDOM indicated the Leadership and Organizational Change for Implementation (LOCI) strategy improved fidelity to measurement-based care (MBC) in youth mental health services. In this study, we tested LOCI\'s hypothesized mechanisms of change, namely: (1) LOCI will improve implementation and transformational leadership, which in turn will (2) mediate LOCI\'s effect on implementation climate, which in turn will (3) mediate LOCI\'s effect on MBC fidelity.
METHODS: Twenty-one outpatient mental health clinics serving youth were randomly assigned to LOCI plus MBC training and technical assistance or MBC training and technical assistance only. Clinicians rated their leaders\' implementation leadership, transformational leadership, and clinic implementation climate for MBC at five time points (baseline, 4-, 8-, 12-, and 18-months post-baseline). MBC fidelity was assessed using electronic metadata for youth outpatients who initiated treatment in the 12 months following MBC training. Hypotheses were tested using longitudinal mixed-effects models and multilevel mediation analyses.
RESULTS: LOCI significantly improved implementation leadership and implementation climate from baseline to follow-up at 4-, 8-, 12-, and 18-month post-baseline (all ps < .01), producing large effects (range of ds = 0.76 to 1.34). LOCI\'s effects on transformational leadership were small at 4 months (d = 0.31, p = .019) and nonsignificant thereafter (ps > .05). LOCI\'s improvement of clinic implementation climate from baseline to 12 months was mediated by improvement in implementation leadership from baseline to 4 months (proportion mediated [pm] = 0.82, p = .004). Transformational leadership did not mediate LOCI\'s effect on implementation climate (p = 0.136). Improvement in clinic implementation climate from baseline to 12 months mediated LOCI\'s effect on MBC fidelity during the same period (pm = 0.71, p = .045).
CONCLUSIONS: LOCI improved MBC fidelity in youth mental health services by improving clinic implementation climate, which was itself improved by increased implementation leadership. Fidelity to EBPs in healthcare settings can be improved by developing organizational leaders and strong implementation climates.
BACKGROUND: ClinicalTrials.gov identifier: NCT04096274. Registered September 18, 2019.

OBJECTIVE: Measurement-based care (MBC), which collects session-by-session symptom data from patients and provides clinicians with feedback on treatment response, is a highly generalizable evidence-based practice with significant potential to improve the outcomes of mental health treatment in youth when implemented with fidelity; however, it is rarely used in community settings. This study tested whether an implementation strategy targeting organizational leadership and organizational implementation climate could improve MBC fidelity and clinical outcomes for youth in outpatient mental health clinics.
METHODS: In a cluster randomized trial, 21 clinics were assigned to the Leadership and Organizational Change for Implementation strategy plus training and technical assistance in MBC (k = 11, n = 117) or training and technical assistance only (k = 10, n = 117). Primary outcomes of MBC fidelity (assessed via electronic metadata) and youth symptom improvement (assessed via caregiver-reported change on the Shortform Assessment for Children Total Problem Score) were collected for consecutively enrolled youths (ages 4-18 years) who initiated treatment in the 12 months following MBC training. Outcomes of each youth were assessed for 6 months following baseline.
RESULTS: A total of 234 youths were enrolled and included in intent-to-treat analyses. At baseline, there were no significant differences by condition in clinic, clinician, or youth characteristics. Youths in clinics using the Leadership and Organizational Change for Implementation strategy experienced significantly higher MBC fidelity compared with youths in control clinics (23.1% vs 3.4%, p = .014), and exhibited significantly greater reductions in symptoms from baseline to 6 months (d = 0.31, 95% CI: 0.04-0.58, p = .023).
CONCLUSIONS: Implementation strategies targeting organizational leadership and focused implementation climate can improve fidelity to evidence-based practices and clinical outcomes of youth mental health services.
BACKGROUND: Working to Implement and Sustain Digital Outcome Measures (WISDOM); https://clinicaltrials.gov/; NCT04096274.

BACKGROUND: Genome-wide association studies (GWAS) are important for the acceleration of crop improvement through knowledge of marker-trait association (MTA). This report used DArT SNP markers to successfully perform GWAS on agro-morphological traits using 270 bambara groundnut [Vigna subterranea (L.) Verdc.] landraces sourced from diverse origins. The study aimed to identify marker traits association for nine agronomic traits using GWAS and their candidate genes. The experiment was conducted at two different locations laid out in alpha lattice design. The cowpea [Vigna unguiculata (L.) Walp.] reference genome (i.e. legume genome most closely related to bambara groundnut) assisted in the identification of candidate genes.
RESULTS: The analyses showed that linkage disequilibrium was found to decay rapidly with an average genetic distance of 148 kb. The broadsense heritability was relatively high and ranged from 48.39% (terminal leaf length) to 79.39% (number of pods per plant). The GWAS identified a total of 27 significant marker-trait associations (MTAs) for the nine studied traits explaining 5.27% to 24.86% of phenotypic variations. Among studied traits, the highest number of MTAs was obtained from seed coat colour (6) followed by days to flowering (5), while the least is days to maturity (1), explaining 5.76% to 11.03%, 14.5% to 19.49%, and 11.66% phenotypic variations, respectively. Also, a total of 17 candidate genes were identified, varying in number for different traits; seed coat colour (6), days to flowering (3), terminal leaf length (2), terminal leaf width (2), number of seed per pod (2), pod width (1) and days to maturity (1).
CONCLUSIONS: These results revealed the prospect of GWAS in identification of SNP variations associated with agronomic traits in bambara groundnut. Also, its present new opportunity to explore GWAS and marker assisted strategies in breeding of bambara groundnut for acceleration of the crop improvement.

<b>Background and Objective:</b> Indonesia consists of various ethnic groups with diverse cultures. However, research on allele frequencies and genetic variations of each ethnic group in Indonesia has not been well established. Therefore, a study was conducted on 13 STR loci panels to analyze the mentawai population as an enhancement of the Indonesian population\'s genetic data library and genetic variation. Mentawai is one of the Indonesian tribes who live on Mentawai Island, West Sumatera. <b>Materials and Methods:</b> The PrepFiler kit to extract DNA from blood and the GlobalFiler kit for amplifying the 13 loci were used. The genetic analyzer ABI PRISM 3500 was used to detect PCR products. Data were processed and analyzed by EasyDNA and FORSTAT software. <b>Results:</b> The allele frequency data for 13 autosomal loci in Mentawai populations were obtained. Expected heterozygosity was found with a minimum of 0.607 for TPOX and a maximum of 0.866 for FGA. Power of discrimination (PD) values ranges from TPOX (0.792) to FGA (0.968). Polymorphic information content (PIC) values for all loci were high, ranging from 0.642 for TPOX to 0.921 for vWA. Three off-ladder alleles in these findings were detected. Allele 6.3 at the TH01 loci and allele 14.2 at the D18S51 loci are exquisite. The mean expected heterozygosity and mean power of discrimination value across the 13 loci were 75.9 and 90.1%, indicating striking gene diversity. <b>Conclusion:</b> These 13 STR loci can be used for population genetic studies and forensic identification.

The GlobalFiler™ PCR Amplification Kit is one of the most sensitive kits that exist today that makes the PCR amplification of human DNA possible. PCR amplification using this specific kit makes millions of copies of 24 specific target sequences in the DNA, called markers or loci. This kit is a 6-dye, short tandem repeat (STR) multiplex assay kit that has a synthetic mix of primers and single-stranded oligonucleotides that are combined with DNA samples and then subjected to 29 or 30 cycles of denaturing, annealing, and extension, as per laboratory protocol. Methods for instrument operation will vary depending on the thermal cycler instrument model that is used. Nevertheless, the GlobalFiler™ PCR Amplification Kit has proven to be a very useful tool to DNA analysts, amplifying extremely low quantities of DNA, making it possible to detect partial, if not full, genetic profiles from a wide range of sample types. This chapter discusses the typical preparation and PCR amplification of human forensic DNA samples, using the GlobalFiler™ PCR Amplification Kit.

Autosomal dominant non-syndromic hearing loss (HL) typically occurs when only one dominant allele within the disease gene is sufficient to express the phenotype. Therefore, most patients diagnosed with autosomal dominant non-syndromic HL have a hearing-impaired parent, although de novo mutations should be considered in all cases of negative family history. To date, more than 50 genes and 80 loci have been identified for autosomal dominant non-syndromic HL. DFNA22 (MYO6 gene), DFNA8/12 (TECTA gene), DFNA20/26 (ACTG1 gene), DFNA6/14/38 (WFS1 gene), DFNA15 (POU4F3 gene), DFNA2A (KCNQ4 gene), and DFNA10 (EYA4 gene) are some of the most common forms of autosomal dominant non-syndromic HL. The characteristics of autosomal dominant non-syndromic HL are heterogenous. However, in most cases, HL tends to be bilateral, post-lingual in onset (childhood to early adulthood), high-frequency (sloping audiometric configuration), progressive, and variable in severity (mild to profound degree). DFNA1 (DIAPH1 gene) and DFNA6/14/38 (WFS1 gene) are the most common forms of autosomal dominant non-syndromic HL affecting low frequencies, while DFNA16 (unknown gene) is characterized by fluctuating HL. A long audiological follow-up is of paramount importance to identify hearing threshold deteriorations early and ensure prompt treatment with hearing aids or cochlear implants.

Alzheimer\'s disease (AD) is the most common neurodegenerative disease in the world. It is classified as familial and sporadic. The dominant familial or autosomal presentation represents 1-5% of the total number of cases. It is categorized as early onset (EOAD; <65 years of age) and presents genetic mutations in presenilin 1 (PSEN1), presenilin 2 (PSEN2), or the Amyloid precursor protein (APP). Sporadic AD represents 95% of the cases and is categorized as late-onset (LOAD), occurring in patients older than 65 years of age. Several risk factors have been identified in sporadic AD; aging is the main one. Nonetheless, multiple genes have been associated with the different neuropathological events involved in LOAD, such as the pathological processing of Amyloid beta (Aβ) peptide and Tau protein, as well as synaptic and mitochondrial dysfunctions, neurovascular alterations, oxidative stress, and neuroinflammation, among others. Interestingly, using genome-wide association study (GWAS) technology, many polymorphisms associated with LOAD have been identified. This review aims to analyze the new genetic findings that are closely related to the pathophysiology of AD. Likewise, it analyzes the multiple mutations identified to date through GWAS that are associated with a high or low risk of developing this neurodegeneration. Understanding genetic variability will allow for the identification of early biomarkers and opportune therapeutic targets for AD.

Brugada syndrome (BrS) is a rare hereditary arrhythmia disorder, with a distinctive ECG pattern, correlated with an increased risk of ventricular arrhythmias and sudden cardiac death (SCD) in young adults. BrS is a complex entity in terms of mechanisms, genetics, diagnosis, arrhythmia risk stratification, and management. The main electrophysiological mechanism of BrS requires further research, with prevailing theories centered on aberrant repolarization, depolarization, and current-load match. Computational modelling, pre-clinical, and clinical research show that BrS molecular anomalies result in excitation wavelength (k) modifications, which eventually increase the risk of arrhythmia. Although a mutation in the SCN5A (Sodium Voltage-Gated Channel Alpha Subunit 5) gene was first reported almost two decades ago, BrS is still currently regarded as a Mendelian condition inherited in an autosomal dominant manner with incomplete penetrance, despite the recent developments in the field of genetics and the latest hypothesis of additional inheritance pathways proposing a more complex mode of inheritance. In spite of the extensive use of the next-generation sequencing (NGS) technique with high coverage, genetics remains unexplained in a number of clinically confirmed cases. Except for the SCN5A which encodes the cardiac sodium channel NaV1.5, susceptibility genes remain mostly unidentified. The predominance of cardiac transcription factor loci suggests that transcriptional regulation is essential to the Brugada syndrome\'s pathogenesis. It appears that BrS is a multifactorial disease, which is influenced by several loci, each of which is affected by the environment. The primary challenge in individuals with a BrS type 1 ECG is to identify those who are at risk for sudden death, researchers propose the use of a multiparametric clinical and instrumental strategy for risk stratification. The aim of this review is to summarize the latest findings addressing the genetic architecture of BrS and to provide novel perspectives into its molecular underpinnings and novel models of risk stratification.