Biomarkers.

Background: The burden of Alzheimer's disease and related dementias is growing fast in Africa. The Recruitment and Retention for Alzheimer's Disease Diversity Genetic Cohorts in the Alzheimer's Disease Sequencing Project (READD-ADSP) has commenced recruitment of 5000 African participants (AD and cognitively unimpaired individuals) to generate genomic and biomarker data to better characterize AD genetic architecture in Africa. Participating countries, part of the African Dementia Consortium (AfDC) include Nigeria, Ghana, Benin, Cameroon, Uganda, Kenya, Ethiopia, Tanzania, and Mozambique.

Public Health.

Background: Understanding the genetic underpinnings of Alzheimer's disease is crucial for advancing research and developing targeted interventions. Genomic research in dementia in Africa is of utmost importance based on recent reports from studies in African Americans that African ancestral gene is associated with lower risk effect for developing AD. However, dementia related genetic study is an evolving research in sub-Saharan Africa with peculiar challenges influencing participant recruitment.

Highly Diastereoselective Access to Densely Functionalized Piperidine Cores of Influenza Endonuclease Inhibitors via a Metal-Free S1 Approach.

A novel, highly diastereoselective, and metal-free synthesis of multisubstituted piperidines via an S1 approach is reported in this study. The method allows for the preparation of highly functionalized compounds with exceptional diastereomeric selectivities and consistently reproducible yields. These compounds are of significant interest due to their remarkable biological activities toward influenza endonuclease.

Eleven Grand Challenges for Inflammatory Bowel Disease Genetics and Genomics.

The past 2 decades have witnessed extraordinary advances in our understanding of the genetic factors influencing inflammatory bowel disease (IBD), providing a foundation for the approaching era of genomic medicine. On behalf of the NIDDK IBD Genetics Consortium, we herein survey 11 grand challenges for the field as it embarks on the next 2 decades of research utilizing integrative genomic and systems biology approaches. These involve elucidation of the genetic architecture of IBD (how it compares across populations, the role of rare variants, and prospects of polygenic risk scores), in-depth cellular and molecular characterization (fine-mapping causal variants, cellular contributions to pathology, molecular pathways, interactions with environmental exposures, and advanced organoid models), and applications in personalized medicine (unmet medical needs, working toward molecular nosology, and precision therapeutics).

Binary vector copy number engineering improves Agrobacterium-mediated transformation.

The copy number of a plasmid is linked to its functionality, yet there have been few attempts to optimize higher-copy-number mutants for use across diverse origins of replication in different hosts. We use a high-throughput growth-coupled selection assay and a directed evolution approach to rapidly identify origin of replication mutations that influence copy number and screen for mutants that improve Agrobacterium-mediated transformation (AMT) efficiency. By introducing these mutations into binary vectors within the plasmid backbone used for AMT, we observe improved transient transformation of Nicotiana benthamiana in four diverse tested origins (pVS1, RK2, pSa and BBR1).

Inno4Vac Workshop Report Part 1: Controlled Human Influenza Virus Infection Model (CHIVIM) Strain Selection and Immune Assays for CHIVIM Studies, November 2021, MHRA, UK.

Controlled human infection models (CHIMs) are a critical tool for the understanding of infectious disease progression, characterising immune responses to infection and rapid assessment of vaccines or drug treatments. There is increasing interest in using CHIMs for vaccine development and an obvious need for widely available and fit-for-purpose challenge agents. Inno4Vac is a large European consortium working towards accelerating and de-risking the development of new vaccines, including the development of CHIMs for influenza, respiratory syncytial virus and Clostridioides difficile.

Outcomes After Osteochondral Allograft Transplantation of the Medial Femoral Condyle in Patients With Varus and Nonvarus Alignment.

Background: Fresh osteochondral allograft (OCA) transplantation is an effective technique for the treatment of focal chondral and osteochondral defects in the knee. Coronal-plane malalignment leads to increased contact forces within a compartment and subsequently the cartilage repair site and may lead to higher failure rates. However, the magnitude of the effect of coronal-plane malalignment on graft survivorship and clinical outcomes has not been well characterized.

Peer Intervention to Link Overdose Survivors to Treatment (PILOT): Protocol for a Multisite, Randomized Controlled Trial Conducted Within the National Institute on Drug Abuse Clinical Trials Network.

Background: The increase in opioid-related overdoses has caused a decrease in average life expectancy, highlighting the need for effective interventions to reduce overdose risk and prevent subsequent overdoses. Peer support specialists (PSSs) offer an appealing strategy to engage overdose survivors and reduce overdose risk, but randomized controlled trials are needed to formalize peer-led interventions and evaluate their effectiveness.

Objective: This National Institute on Drug Abuse Clinical Trials Network (CTN) study is a multisite, prospective, pilot randomized (1:1) controlled trial (CTN protocol 0107) that aims to evaluate the effectiveness of an emergency department (ED)-initiated, peer-delivered intervention tailored for opioid overdose survivors (Peer Intervention to Link Overdose survivors to Treatment [PILOT]), compared with treatment as usual (TAU).

Ancestral Diversity in Pharmacogenomics Affects Treatment for Hispanic/Latine Populations With Inflammatory Bowel Disease.

Background And Aims: The prevalence of inflammatory bowel disease among Hispanic/Latine communities is increasing. Pharmacogenomic studies reveal genetic markers that influence treatment decisions. The aim of our study was to examine the frequency and impact of genetic polymorphisms on thiopurine-associated leukopenia (NUDT15, TPMT) and anti-tumor necrosis factor (TNF) immunogenicity (HLA-DQA1∗05) in a cohort of Hispanic patients of diverse ancestral backgrounds.

Electronic Health Record-Based Screening for Intimate Partner Violence: A Cluster Randomized Clinical Trial.

Importance: Intimate partner violence (IPV) is a significant public health issue, with a 25% lifetime prevalence. Screening for IPV in primary care is a recommended practice whose effectiveness is debated.

Objective: To assess the effect of an electronic health record (EHR)-based multifactorial intervention screening on the detection of IPV risk in primary care practice.

Novel Pan-Coronavirus 3CL Protease Inhibitor MK-7845: Biological and Pharmacological Profiling.

Severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) continues to be a global threat due to its ability to evolve and generate new subvariants, leading to new waves of infection. Additionally, other coronaviruses like Middle East respiratory syndrome coronavirus (MERS-CoV, formerly known as hCoV-EMC), which first emerged in 2012, persist and continue to present a threat of severe illness to humans. The continued identification of novel coronaviruses, coupled with the potential for genetic recombination between different strains, raises the possibility of new coronavirus clades of global concern emerging.

Trajectories of positive affect in autistic individuals during the transition to adulthood.

Recent research has revealed informative patterns about health, mental health, self-help skills, autism symptoms, and social skills during the transition to adulthood for autistic individuals. This study expands on these findings by examining how positive affect (e.g.

Bioinformatic Prediction and High Throughput In Vivo Screening to Identify Cis-Regulatory Elements for the Development of Algal Synthetic Promoters.

Algae biotechnology holds immense promise for revolutionizing the bioeconomy through the sustainable and scalable production of various bioproducts. However, their development has been hindered by the lack of advanced genetic tools. This study introduces a synthetic biology approach to develop such tools, focusing on the construction and testing of synthetic promoters.

Corrigendum: Understanding profound autism: implications for stigma and supports.

[This corrects the article DOI: 10.3389/fpsyt.2024.

Who Benefits from Manipulation under Anesthesia Following Total Knee Arthroplasty?

Arthrofibrosis is a multifactorial process that results in decreased knee range of motion (ROM). Manipulation under anesthesia (MUA) is commonly regarded as the preferred initial treatment of arthrofibrosis following total knee arthroplasty (TKA). There have been no well-controlled studies demonstrating that MUA effectively increases ROM in patients who develop arthrofibrosis after TKA when compared with routine care.

Opportunities and challenges for T cell-based influenza vaccines.

Vaccination remains our main defence against influenza, which causes substantial annual mortality and poses a serious pandemic threat. Influenza virus evades immunity by rapidly changing its surface antigens but, even when the vaccine is well matched to the current circulating virus strains, influenza vaccines are not as effective as many other vaccines. Influenza vaccine development has traditionally focused on the induction of protective antibodies, but there is mounting evidence that T cell responses are also protective against influenza.

Integrated high performance microfluidic organic analysis instrument for planetary and space exploration.

The exploration of our solar system to characterize the molecular organic inventory will enable the identification of potentially habitable regions and initiate the search for biosignatures of extraterrestrial life. However, it is challenging to perform the required high-resolution, high-sensitivity chemical analyses in space and in planetary environments. To address this challenge, we have developed a microfluidic organic analyzer (MOA) instrument that consists of a multilayer programmable microfluidic analyzer (PMA) for fluidic processing at the microliter scale coupled with a microfabricated glass capillary electrophoresis (CE) wafer for separation and analysis of the sample components.

Characterization of peer support services for substance use disorders in 11 US emergency departments in 2020: findings from a NIDA clinical trials network site selection process.

Introduction: Emergency departments (ED) are incorporating Peer Support Specialists (PSSs) to help with patient care for substance use disorders (SUDs). Despite rapid growth in this area, little is published regarding workflow, expectations of the peer role, and core components of the PSS intervention. This study describes these elements in a national sample of ED-based peer support intervention programs.

Participation in Sports or Recreational Activities After Osteochondral Allograft Transplantation of the Talus.

Background: Fresh osteochondral allograft (OCA) transplantation is a viable treatment option for osteochondral defects of the talus. However, sufficient data are not available on patients' participation in sports or recreational activities after the procedure.

Purpose: To assess whether patients undergoing OCA transplantation of the talus participated in sports or recreational activities postoperatively.

Enhanced phenotypes for identifying opioid overdose in emergency department visit electronic health record data.

Background: Accurate identification of opioid overdose (OOD) cases in electronic healthcare record (EHR) data is an important element in surveillance, empirical research, and clinical intervention. We sought to improve existing OOD electronic phenotypes by incorporating new data types beyond diagnostic codes and by applying several statistical and machine learning methods.

Materials And Methods: We developed an EHR dataset of emergency department visits involving OOD cases or patients considered at risk for an OOD and ascertained true OOD status through manual chart reviews.