Haploinsufficiency of ITSN1 is associated with a substantial increased risk of Parkinson's disease.

Despite its significant heritability, the genetic basis of Parkinson's disease (PD) remains incompletely understood. Here, in analyzing whole-genome sequence data from 3,809 PD cases and 247,101 controls in the UK Biobank, we discover that protein-truncating variants in ITSN1 confer a substantially increased risk of PD (p = 6.1 × 10; odds ratio [95% confidence interval] = 10.

Safety and immunogenicity in humans of enterotoxigenic Escherichia coli double mutant heat-labile toxin administered intradermally.

Enterotoxigenic Escherichia coli (ETEC) diarrhea is associated with a high burden of disease globally, for which no licensed vaccine is available. A Phase 1, double-blind, dose-escalation (0.1-2.

A single-cell transcriptomic map of the developing Atoh1 lineage identifies neural fate decisions and neuronal diversity in the hindbrain.

Proneural transcription factors establish molecular cascades to orchestrate neuronal diversity. One such transcription factor, Atonal homolog 1 (Atoh1), gives rise to cerebellar excitatory neurons and over 30 distinct nuclei in the brainstem critical for hearing, breathing, and balance. Although Atoh1 lineage neurons have been qualitatively described, the transcriptional programs that drive their fate decisions and the full extent of their diversity remain unknown.

Optimizing the measurement of sample entropy in resting-state fMRI data.

Introduction: The complexity of brain signals may hold clues to understand brain-based disorders. Sample entropy, an index that captures the predictability of a signal, is a promising tool to measure signal complexity. However, measurement of sample entropy from fMRI signals has its challenges, and numerous questions regarding preprocessing and parameter selection require research to advance the potential impact of this method.

Recombinant Full-length Plasmodium falciparum Circumsporozoite Protein-Based Vaccine Adjuvanted With Glucopyranosyl Lipid A-Liposome Quillaja saponaria 21: Results of Phase 1 Testing With Malaria Challenge.

Background: Malaria is preventable yet causes >600 000 deaths annually. RTS,S, the first marketed malaria vaccine, has modest efficacy, but improvements are needed for eradication.

Methods: We conducted an open-label, dose escalation phase 1 study of a full-length recombinant circumsporozoite protein vaccine (rCSP) administered with adjuvant glucopyranosyl lipid A-liposome Quillaja saponaria 21 formulation (GLA-LSQ) on days 1, 29, and 85 or 1 and 490 to healthy, malaria-naive adults.

Interpersonal communication, cultural norms, and community perceptions associated with care-seeking for fever among children under age five in Magoé district, Mozambique.

Background: Malaria is endemic throughout Mozambique, contributing significantly to the country's burden of disease. Prompt and effective treatment for fevers in children can limit the mortality and morbidity impacts of the disease but many children in the country are not taken for formal care when ill. Using an ideational model of behaviour, this study assesses the magnitude of the relationships for potential drivers of care-seeking, including interpersonal communication, malaria messaging, and knowledge and attitudes about malaria, with actual care-seeking behaviours for under-five children with fever in Magoé district, Mozambique.

drives the heterogeneity of the pontine nuclei neurons and promotes their differentiation.

Pontine nuclei (PN) neurons mediate the communication between the cerebral cortex andthe cerebellum to refine skilled motor functions. Prior studies showed that PN neurons fall into two subtypes based on their anatomic location and region-specific connectivity, but the extent of their heterogeneity and its molecular drivers remain unknown. encodes a transcription factor that is expressed in the PN precursors.

Malaria-Related Psychosocial Factors, Past Antenatal Care-Seeking Behaviors, and Future Antenatal Care-Seeking Intentions by Maternal Age in Malawi and Democratic Republic of the Congo.

Young women in sub-Saharan Africa are a group at increased risk for malaria in pregnancy. Early antenatal care (ANC) seeking makes it more likely that women will receive the recommended doses of intermittent preventive treatment of malaria in pregnancy. This study used data from national Malaria Behavior Surveys conducted in Malawi and the Democratic Republic of the Congo (DRC) in 2021 to explore the association between intention to attend ANC in the first trimester for a future pregnancy (early ANC intention) and psychosocial factors among women aged 15-49 years.

Ideational factors and their association with insecticide treated net use in Magoe District, Mozambique.

Background: Insecticide treated bed nets (ITN) are considered a core malaria vector control tool by the WHO and are the main contributor to the large decline in malaria burden in sub-Saharan Africa over the past 20 years, but they are less effective if they are not broadly and regularly used. ITN use may depend on factors including temperature, relative humidity, mosquito density, seasonality, as well as ideational or psychosocial factors including perceptions of nets and perceptions of net use behaviours.

Methods: A cross-sectional household survey was conducted as part of a planned randomized controlled trial in Magoe District, Mozambique.

Histopathologic Features of Breast Tissue From Transgender Men and Their Associations With Androgen Therapy.

Objectives: To assess the histopathologic features of breast tissue of transgender men (TM) undergoing gender-affirming bilateral mastectomies in relation to androgen therapy (AT).

Methods: We reviewed 374 transgender bilateral mastectomy cases from 2017 to 2020. Of these, 314 (84.

Evaluation of a Geographic Screening Protocol for Chronic Parasitic Infections Before Kidney Transplant: An Institutional Experience in Minnesota.

Pretransplant recommendations advise risk-based screening for strongyloidiasis, schistosomiasis, and Chagas disease. We evaluated the implementation of a chronic parasite screening protocol at a health system in a nonendemic region serving a large foreign-born population. Candidates listed for kidney transplant at Hennepin Healthcare (Minneapolis, MN) between 2010 and 2020 were included.

Hospital pharmacy acquisition of nonstocked antimicrobials-current processes and areas for improvement.

Background: The delivery of prompt and appropriate antimicrobial therapy for life-threatening infections is an important antimicrobial stewardship measure and a priority for hospitals.

Objectives: To better understand U.S.

A genetically engineered parasite vaccine provides protection from controlled human malaria infection.

Genetically engineered live sporozoites constitute a potential platform for creating consistently attenuated, genetically defined, whole-parasite vaccines against malaria through targeted gene deletions. Such genetically attenuated parasites (GAPs) do not require attenuation by irradiation or concomitant drug treatment. We previously developed a (Pf) GAP with deletions in , , and genes (PfGAP3KO) and demonstrated its safety and immunogenicity in humans.

Passive Clearing and 3D Lightsheet Imaging of the Intact and Injured Spinal Cord in Mice.

The spinal cord contains a diverse array of sensory and motor circuits that are essential for normal function. Spinal cord injury (SCI) permanently disrupts neural circuits through initial mechanical damage, as well as a cascade of secondary injury events that further expand the spinal cord lesion, resulting in permanent paralysis. Tissue clearing and 3D imaging have recently emerged as promising techniques to improve our understanding of the complex neural circuitry of the spinal cord and the changes that result from damage due to SCI.

Implementing a Physical Activity Consultation Clinic during a Global Pandemic.

Ten percent of all premature deaths and 117 billion dollars in annual health care costs are attributable to physical inactivity in America. The positive impact exercise can have on overall health is irrefutable. While it is the responsibility of health care providers to assess and counsel for exercise, there are logistical, structural, and educational barriers preventing this counseling.

Axial elongation of caudalized human organoids mimics aspects of neural tube development.

Axial elongation of the neural tube is crucial during mammalian embryogenesis for anterior-posterior body axis establishment and subsequent spinal cord development, but these processes cannot be interrogated directly in humans as they occur post-implantation. Here, we report an organoid model of neural tube extension derived from human pluripotent stem cell (hPSC) aggregates that have been caudalized with Wnt agonism, enabling them to recapitulate aspects of the morphological and temporal gene expression patterns of neural tube development. Elongating organoids consist largely of neuroepithelial compartments and contain TBXT+SOX2+ neuro-mesodermal progenitors in addition to PAX6+NES+ neural progenitors.

Low back pain in youth: Recognizing red flags.

Although low back pain in children and teens is usually benign, recognizing red flags that indicate the need for imaging, referral, bracing, or surgery is critical.

School-Based Serosurveys to Assess the Validity of Using Routine Health Facility Data to Target Malaria Interventions in the Central Highlands of Madagascar.

Background: In low-malaria-transmission areas of Madagascar, annual parasite incidence (API) from routine data has been used to target indoor residual spraying at subdistrict commune level. To assess validity of this approach, we conducted school-based serological surveys and health facility (HF) data quality assessments in 7 districts to compare API to gold-standard commune-level serological measures.

Methods: At 2 primary schools in each of 93 communes, 60 students were randomly selected with parents and teachers.

Author Correction: V2a interneuron differentiation from mouse and human pluripotent stem cells.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

V2a interneuron differentiation from mouse and human pluripotent stem cells.

V2a interneurons are located in the hindbrain and spinal cord, where they provide rhythmic input to major motor control centers. Many of the phenotypic properties and functions of excitatory V2a interneurons have yet to be fully defined. Definition of these properties could lead to novel regenerative therapies for traumatic injuries and drug targets for chronic degenerative diseases.

Evaluating the quality of routinely reported data on malaria commodity stocks in Guinea, 2014-2016.

Background: Ensuring malaria commodity availability at health facilities is a cornerstone of malaria control. Since 2013, the Guinea National Malaria Control Programme has been routinely collecting data on stock levels of key malaria commodities through a monthly routine malaria information system (RMIS). In parallel, biannual end-user verification (EUV) surveys have also assessed malaria commodity availability at a subset of health facilities, potentially representing a duplication of efforts.