Basic Science and Pathogenesis.

The Alzheimer's Disease Sequencing Project (ADSP) has used whole genome sequencing, computational approaches, and epidemiological and statistical expertise to accelerate understanding of the fundamental mechanisms of Alzheimer disease and related disorders (ADRD). Going forward, the ADSP will continue growing to over 110,000 participants to further dissect the risk for AD. To move towards novel insights, the ADSP is adopting new approaches while leveraging the rich existing data.

Basic Science and Pathogenesis.

Background: The "Recruitment and Retention for Alzheimer's Disease Diversity Genetic Cohorts in the ADSP (READD-ADSP)" is developing a resource to expand ancestral diversity in Alzheimer disease (AD) studies to dissect the genetic architecture of AD across different populations. In addition to US sites, READD-ADSP includes four US sites and nine countries in sub-Saharan Africa through the Africa Dementia Consortium (AfDC). The overall goal of READD-ADSP is to identify genetically driven targets in diverse groups including African Americans and Hispanic/Latinos in US, and Africans.

Basic Science and Pathogenesis.

As part of the goal of the ADSP to develop effect therapeutic for AD, it has become imperative to develop therapeutic targets for APOE4. The Apolipoprotein E4 gene (APOE4) strongest genetic risk factor for AD and is present in 64% of sporadic, late-onset AD, with a recent prevalence estimate of 245 million carriers worldwide. A key question is whether APOE4 is a toxic or gain of function allele or alternatively if its effect is due to a loss or partial loss of function.

Clinical Manifestations.

Background: The Clinical Dementia Rating Scale (CDR) is a gold standard metric for staging the nature and severity of global cognitive and functional impairment in Alzheimer's disease (AD) and other dementias. Prior evidence from older and/or smaller samples suggests that The Quick Dementia Rating System (QDRS) informant questionnaire provides results comparable to the CDR and can be completed in just 3-5 minutes, sans a trained clinician or rater. This study aimed to: 1) investigate concordance between the QDRS-derived global CDR ("QDRS-global"; Galvin, 2015) and CDR-global scores; 2) examine item-level QDRS/CDR agreement; and (3) evaluate QDRS-global/CDR-global concordant/discordant groups against concurrent Preclinical Alzheimer's Cognitive Composite (PACC3) performance.

Clinical Manifestations.

Background: Evidence suggests that mindfulness practice may reduce the risk of dementia by enhancing cognitive reserve. However, it's unclear whether APOE ε4 carrier status influences the link between mindfulness and cognitive reserve. This study examined whether associations between mindfulness and memory, language, executive and speed reserve differed by APOE ε4 carrier status.

Clinical Manifestations.

Background: The utility of neuropsychological measures commonly used to diagnose individuals with suspected MCI or AD was recently explored in European cohorts, however their utility in Caribbean Hispanic (CH) populations is not well understood.

Method: Our sample consisted of 507 CH individuals from ongoing studies of Puerto Rican and Cuban American older adults (74%% Female, mean age = 74.1, mean education = 12.

Clinical Manifestations.

Background: Gait and balance deficiencies may be important indicators of cognitive impairment, distinguishing dementia from normal cognition (NC). It is unclear whether this extends to pre-dementia stages of disease. Study goals were to: assess patterns of mobility across early stages of disease and identify specific measures that distinguish individuals with subjective cognitive impairment (SCI) and mild cognitive impairment (MCI).

Clinical Manifestations.

Background: When performing a picture description task, healthy individuals tend to look only briefly at a target before beginning its description, after which they move promptly onto the next target. This sequence may be disrupted in those with cognitive impairment. Just as cognitively impaired individuals produce greater numbers of disfluencies and pauses, those with mild cognitive impairment (MCI) may delay speech production by extending their gaze behavior towards a target before beginning its description.

Clinical Manifestations.

Background: Age-related cognitive decline (ARCD) refers to the cognitive changes that occur in individuals because of aging. Research suggests that the underlying mechanism behind ARCD is a loss of synaptic plasticity and altered dendritic spine morphology. Similarly, the cognitive changes in Alzheimer's Disease (AD) are also thought to arise from impaired synaptic plasticity and dendritic spine loss.

Clinical Manifestations.

Background: Over 13,000 individuals from both domestic and African sites will be collected for the READD-ADSP study. Adjudicating this number of individuals is challenging, so we evaluated knowledge-based decision tree algorithms to predict clinical diagnoses using nationally representative norms and standard cut-offs. Additional models were constructed using culturally adjusted cut-offs, domain average cut-offs, and exclusion of the Trail Making Test (TMT) which performed poorly.

Investigating Moral Distress in Clinical Research Professionals-A Deep Dive into Troubled Waters.

Moral distress occurs when professionals are constrained from taking what they believe to be ethically appropriate actions or are forced to take actions they believe are ethically inappropriate, challenging their professional identities and representing systems-level issues within organizations. Moral distress has been recognized in a variety of health care-related fields; however, the phenomenon is still comparatively unexplored among clinical research professionals (CRPs). In this qualitative study, we interviewed ten CRPs to unearth root causes of moral distress in this ethically unique profession.

The African Initiative for Bioinformatics Online Training in Neurodegenerative Diseases (AI-BOND): Investing in the next generation of African neuroscientists.

Unlabelled: Neurodegenerative disorders, including Alzheimer's disease and AD-related dementias (AD/ADRD), pose significant challenges to health care systems globally, particularly in Africa. With the advances in medical technology and research capabilities, especially in next-generation sequencing and imaging, vast amounts of data have been generated from AD/ADRD research. Given that the greatest increase in AD/ADRD prevalence is expected to occur in Africa, it is critical to establish comprehensive bioinformatics training programs to help African scientists leverage existing data and collect additional information to untangle AD/ADRD heterogeneity in African populations.

Genome sequencing reveals novel variants in a diverse population with congenital anterior segment anomalies.

Congenital anterior segment anomalies are disorders that affect the development of the eye and cause severe visual impairment. The molecular basis of congenital anterior segment anomalies is not well known. In this study, genome sequencing was performed on 27 families from diverse ethnicities with congenital anterior segment anomalies and 11 variants were identified, most of which were novel and family specific.

Single-nuclei sequencing reveals a robust corticospinal response to nearby axotomy but overall insensitivity to spinal injury.

The ability of neurons to sense and respond to damage is crucial for maintaining homeostasis and facilitating nervous system repair. For some cell types, notably dorsal root ganglia (DRG) and retinal ganglion cells (RGCs), extensive profiling has uncovered a significant transcriptional response to axon injury, which influences survival and regenerative outcomes. In contrast, the injury responses of most supraspinal cell types, which display limited regeneration after spinal damage, remain mostly unknown.

Mutation Causing Pediatric Macular Chorioretinal Atrophy Associated With Stickler Syndrome.

To report a case of macular chorioretinal atrophy associated with Stickler syndrome in a pediatric patient with a genetically confirmed mutation. A single case was evaluated. A 3-year-old girl was found to have macular chorioretinal atrophy in the right eye and a retinal detachment in the left eye.

Accuracy of warm ischemia time measurement using a surgical intelligence software in partial nephrectomies: A validation study.

Objectives: The objectives of this study are to compare the accuracy of warm ischemia times (WITs) derived by a surgical artificial intelligence (AI) software to those documented in surgeon operative reports during partial nephrectomy procedures and to assess the potential of this technology in evaluating postoperative renal function.

Patients And Methods: A surgical AI software (Theator Inc., Palo Alto, CA) was used to capture and analyse videos of partial nephrectomies performed between October 2023 and April 2024.

hnRNPLL regulates MYOF alternative splicing and correlates with early metastasis in pancreatic ductal adenocarcinoma.

Pancreatic ductal adenocarcinoma (PDAC) is a deadly cancer known for its high rate of early metastasis, necessitating the discovery of the underlying mechanisms. Herein, we report that heterogeneous nuclear ribonucleoprotein L-like (hnRNPLL) expression significantly increases at the invasion forefront in PDAC and is associated with early metastasis and poor prognosis. Our findings revealed that hnRNPLL knockdown resulted in extensive exon skipping (ES) events.

Brain Metastasis in Triple-Negative Breast Cancer.

Background: Breast cancer is an important cause of cancer-related death in women worldwide and represents the second most frequent cause of brain metastases after lung cancer. The aim of this study was to determine the characteristics and outcomes of triple-negative breast cancer (TNBC) patients with brain metastasis (BM).

Methods: We retrospectively reviewed a cohort of patients diagnosed with TNBC at the "Instituto Nacional de Enfermedades Neoplasicas" (period 2000-2014) to evaluate patients who developed BM.

Characteristics and Guardianship Status of Children Undergoing Forensic Medical and Psychological Evaluation for Asylum in Miami.

To add to the limited evidence on forensic medical and psychological evaluations of children experiencing distress migration and seeking asylum in the United States, this paper describes the sociodemographic characteristics, nature of human rights violations, and guardianship status of the children served by the Human Rights Clinic of Miami from 2010 to 2021. Through a retrospective study of affidavits, we identified trends among sociodemographic characteristics and types of human rights violations and used bivariate analysis to determine factors associated with guardianship. Children constituted 17% of all evaluations conducted during this period.

Congenital urinary tract anomalies are a variable finding associated with nevoid basal cell carcinoma syndrome.

Introduction: Nevoid basal cell carcinoma syndrome (NBCCS) is a rare autosomal dominant disorder classically associated with multiple basal cell carcinomas, odontogenic keratocysts and skeletal anomalies. However, its significant phenotypic heterogeneity often delays the diagnosis. Here, we undertake the first comprehensive characterisation of NBCCS and congenital urinary tract anomalies.

Systematic Review and Meta-Analysis of OCT measurements in patients with chronic kidney disease.

Purpose: To assess neurodegeneration and chorioretinal thickness in subjects with and without chronic kidney disease (CKD).

Methods: PubMed, Web of Science, Scopus and Embase were searched using proper keywords for articles published in the English language from their inception until January 2024. Publications were included if they reported optical coherence tomography (OCT) measurements of retinal or choroidal layers in patients with CKD compared to healthy or non-CKD controls.

Willingness to Use Oral and Long-Acting Injectable PrEP in Substance-Using Men who have Sex with Men (SU-MSM) in High HIV Incidence Southern U.S. Cities: A NIDA Clinical Trials Network Study.

In Southern U.S. states with high HIV incidence and low HIV Pre-Exposure Prophylaxis (PrEP) uptake, enhanced efforts to increase interest in and willingness to use PrEP are needed.

Cervical spinal decompression and fusion in the setting of Wolcott-Rallison Syndrome: a rare pediatric indication and its surgical considerations.

Wolcott-Rallison Syndrome is an extremely rare syndrome characterized by infantile non-autoimmune diabetes, extensive skeletal dysplasia, and multi-organ failure requiring transplant. Prognosis is very poor, and as such, surgical intervention for symptomatic cervical spine compromise in pediatric patients has not been widely reported in part due to their high fragility. We report a complex case of Wolcott-Rallison Syndrome that presented with cervical myelopathy due to cervicomedullary compression and the exceptional surgical considerations required for successful intervention.