Clinical Trial: Study to Investigate the Efficacy and Safety of the Alpha-2-Delta Ligand PD-217,014 in Patients With Irritable Bowel Syndrome.

Introduction: Despite the emergence of drugs to treat irritable bowel syndrome (IBS), improving abdominal pain can still be challenging. αδ ligands, such as gabapentin and pregabalin, are sometimes used off-label to tackle this problem. However, evidence for efficacy is limited, and no large-scale studies have been published.

Assessing Clinical Improvement of Infants Hospitalized for Respiratory Syncytial Virus-Related Critical Illness.

Background: Pediatric respiratory syncytial virus (RSV)-related acute lower respiratory tract infection (LRTI) commonly requires hospitalization. The Clinical Progression Scale Pediatrics (CPS-Ped) measures level of respiratory support and degree of hypoxia across a range of disease severity, but it has not been applied in infants hospitalized with severe RSV-LRTI.

Methods: We analyzed data from a prospective surveillance registry of infants hospitalized for RSV-related complications across 39 U.

Socioeconomic Disparities in Exposures to PFAS and Other Unregulated Industrial Drinking Water Contaminants in US Public Water Systems.

Background: Unregulated contaminants in drinking water, such as per- and polyfluoroalkyl substances (PFAS), can contribute to cumulative health risks, particularly in overburdened and less-advantaged communities. To our knowledge, there has been no nationwide assessment of socioeconomic disparities in exposures to unregulated contaminants in drinking water.

Objective: The goals of this study were to identify determinants of unregulated contaminant detection among US public water systems (PWSs) and evaluate disparities related to race, ethnicity, and socioeconomic status.

Critical reflection and action in response to an anti-immigration context: What we can learn from migrant young adults from Latin America.

Migrant youth from Latin America who arrive in the United States are faced with a social and political context that dehumanizes migrants of color. These anti-immigrant sentiments become reflected in federal and state policies that deny migrants rights to freedom and safety. The present paper examined how the U.

Enhanced sampling of robust molecular datasets with uncertainty-based collective variables.

Generating a dataset that is representative of the accessible configuration space of a molecular system is crucial for the robustness of machine-learned interatomic potentials. However, the complexity of molecular systems, characterized by intricate potential energy surfaces, with numerous local minima and energy barriers, presents a significant challenge. Traditional methods of data generation, such as random sampling or exhaustive exploration, are either intractable or may not capture rare, but highly informative configurations.

Health Care Resource Utilization With Dronedarone Versus Sotalol Following Catheter Ablation in Adults With Atrial Fibrillation.

Background: Clinical trials support dronedarone use for atrial fibrillation (AF) following catheter ablation (CA); however, comparative data on health care resource utilization (HCRU) with other antiarrhythmic drugs are lacking.

Methods: Retrospective analysis of Merative MarketScan databases (January 01, 2012-March 31, 2020) comparatively assessed HCRU in US adults with AF who received dronedarone or sotalol post-CA. Patients with ≥ 12-months' pre-CA data were followed from post-CA index treatment to disenrollment, death, or study end.

White Matter Tract Crossing and Bottleneck Regions in the Fetal Brain.

There is a growing interest in using diffusion MRI to study the white matter tracts and structural connectivity of the fetal brain. Recent progress in data acquisition and processing suggests that this imaging modality has a unique role in elucidating the normal and abnormal patterns of neurodevelopment in utero. However, there have been no efforts to quantify the prevalence of crossing tracts and bottleneck regions, important issues that have been investigated for adult brains.

Synthesis of Chiral Saturated Heterocycles Bearing Quaternary Centers via Enantioselective β-C(sp)-H Activation of Lactams.

The development of catalytic methods for the synthesis of enantiopure saturated heterocycles has been a long-standing challenge in asymmetric catalysis. We describe the first highly enantioselective palladium-catalyzed βC(sp)-H arylation and olefination of lactams for the preparation of various chiral N-heterocycles bearing quaternary carbon centers. The presence of strongly electron-withdrawing groups on the chiral bifunctional MPAThio ligand is crucial to the reactivity of weakly coordinating lactams.

RNA Translocation through Protein Nanopores: Interlude of the Molten RNA Globule.

Direct translocation of RNA with secondary structures using single-molecule electrophoresis through protein nanopores shows significant fluctuations in the measured ionic current, in contrast to unstructured single-stranded RNA or DNA. We developed a multiscale model combining the oxRNA model for RNA with the 3-dimensional Poisson-Nernst-Planck formalism for electric fields within protein pores, aiming to map RNA conformations to ionic currents as RNA translocates through three protein nanopores: α-hemolysin, CsgG, and MspA. Our findings reveal three distinct stages of translocation (pseudoknot, melting, and molten globule) based on contact maps and current values.

Olfactory Cleft Opacification Improves With Intranasal Steroid Treatment and Is Correlated With Objective and Patient-Reported Olfactory Outcomes.

In patients with severe olfactory and gustatory dysfunction, olfactory cleft opacification improves with expanded intranasal steroid treatment (EDS-FLU) relative to placebo. This is directly associated with objective and patient-reported taste/smell improvement.

EV-idence uncovered: kidney-on-chip study links circulating EVs of cardiorenal syndrome to renal pathology.

The intertwined nature of cardiac and renal failure, where dysfunction in one organ predicts a poor outcome in the other, has long driven the interest in uncovering the exact molecular links between the two. Elucidating the mechanisms driving Cardiorenal Syndrome (CRS) will enable the development of targeted therapies that disrupt this detrimental cycle, potentially improving outcomes for patients. A recent study by Chatterjee .

Identifying cognitive test scores associated with early tau burden in Alzheimer's disease.

Introduction: This study aimed to identify cognitive tests that optimally relate to tau positron emission tomography (PET) signal in the inferior temporal cortex (ITC), a neocortical region associated with early tau accumulation in Alzheimer's disease (AD).

Methods: We analyzed cross-sectional data from the harvard aging brain study (HABS) (= 128) and the Anti-Amyloid Treatment in Asymptomatic Alzheimer's (A4) study (= 393). We used elastic net regression to identify the most robust cognitive correlates of tau PET signal in the ITC.

Computerized cognitive testing to capture cognitive decline in Alzheimer's disease: Longitudinal findings from the ARMADA study.

Introduction: Timely detection and tracking of Alzheimer's disease (AD) -related cognitive decline has become a public health priority. We investigated whether the NIH Toolbox for Assessment of Neurological and Behavioral Function-Cognition Battery (NIHTB-CB) detects AD-related cognitive decline.

Methods:  = 171 participants (age 76.

Validating and utilizing dried blood spots for family screening: Screening Programme Providing Outreach for Testing Hereditary Angioedema (SPPOT-HAE).

Background: Hereditary angioedema (HAE) is a rare genetic disorder with potentially life-threatening consequences, traditionally diagnosed by conventional laboratory methods that can be resource intensive and inconvenient. Incorporating dried blood spot (DBS) tests may be a promising alternative for diagnosing HAE and family screening.

Objective: This study aimed to validate DBS with conventional laboratory assays among confirmed C1 esterase inhibitor (C1-INH) HAE patients and assess the utility of DBS in a Screening Programme Providing Outreach for Testing Hereditary Angioedema (SPPOT-HAE).

Development of a latency model for HIV-1 subtype C and the impact of long terminal repeat element genetic variation on latency reversal.

Sub-Saharan Africa accounts for almost 70 % of people living with HIV (PLWH) worldwide, with the greatest numbers centred in South Africa where 98 % of infections are caused by subtype C (HIV-1C). However, HIV-1 subtype B (HIV-1B), prevalent in Europe and North America, has been the focus of most cure research and testing despite making up only 12 % of HIV-1 infections globally. Development of latency models for non-subtype B viruses is a necessary step to address this disproportionate focus.

Does fragmented sleep mediate the relationship between deficits in sleep spindles and memory consolidation in schizophrenia?

Study Objectives: Sleep spindles, defining electroencephalographic oscillations of nonrapid eye movement (NREM) stage 2 sleep (N2), mediate sleep-dependent memory consolidation (SDMC). Spindles are also thought to protect sleep continuity by suppressing thalamocortical sensory relay. Schizophrenia is characterized by spindle deficits and a correlated reduction of SDMC.

Pivotal Trial Toward Effectiveness of Self-administered OCT in Neovascular Age-related Macular Degeneration. Report 2-Artificial Intelligence Analytics.

Purpose: To validate the performance of the Notal OCT Analyzer (NOA) in processing self-administered OCT images from an OCT system designed for home use (home OCT [HOCT]) as part of a pivotal study aimed at achieving de novo United States Food and Drug Admininstration marketing authorization.

Design: A prospective quantitative cross-sectional artificial intelligence study.

Participants: The study enrolled adults aged ≥55 years diagnosed with neovascular age-related macular degeneration (nAMD) in ≥1 eligible eye with a best-corrected visual acuity of 20/320 or better.

Visual Acuity, Full-field Stimulus Thresholds, and Electroretinography for 4 Years in The Rate of Progression of USH2A-related Retinal Degeneration (RUSH2A) Study.

Purpose: To describe progression of best-corrected visual acuity (BCVA), full-field stimulus thresholds (FST), and electroretinography (ERG) over 4 years in the -related Retinal Degeneration study and to assess their suitability as clinical trial endpoints.

Design: Prospective natural history study.

Participants: Participants (n = 105) with biallelic disease-causing sequence variants in USH2A and BCVA letter scores of ≥54 were included.

N-Arylsulfonylated C-Homoaporphines as a New Class of Antiplatelet and Antimicrobial Agents.

A series of novel N-arylsulfonylated C-homoaporphine alkaloids were synthesized under microwave irradiation and evaluated for their antiplatelet and antimicrobial activities. Among the series, compounds , , , , , , , , and demonstrated highly potent (∼3-fold) platelet aggregation inhibitory activity than acetylsalicylic acid (IC = 21.34 μg/mL).

Advanced Restriction Imaging and Reconstruction Technology for Prostate Magnetic Resonance Imaging (ART-Pro): A Study Protocol for a Multicenter, Multinational Trial Evaluating Biparametric Magnetic Resonance Imaging and Advanced, Quantitative Diffusion Magnetic Resonance Imaging for the Detection of Prostate Cancer.

Multiparametric magnetic resonance imaging (mpMRI) is strongly recommended by current clinical guidelines for improved detection of clinically significant prostate cancer (csPCa). However, the major limitations are the need for intravenous (IV) contrast and dependence on reader expertise. Efforts to address these issues include use of biparametric magnetic resonance imaging (bpMRI) and advanced, quantitative magnetic resonance imaging (MRI) techniques.

Multimodal fluorescence-optoacoustic imaging of the near-infrared calcium ion indicator NIR-GECO2G.

Measuring whole-brain distributed functional activity is an important unmet need in neuroscience, requiring high temporal resolution and cellular specificity across large volumes. Functional optoacoustic neuro-tomography (FONT) with genetically encoded calcium ion indicators is a promising approach towards this goal. However, it has not yet been applied in the near-infrared (NIR) range that provides deep penetration and low vascular background optimal for neuroimaging.

Deep learning model to diagnose cardiac amyloidosis from haematoxylin/eosin-stained myocardial tissue.

Aims: Amyloid deposition in myocardial tissue is a definitive feature for diagnosing cardiac amyloidosis, though less invasive imaging modalities such as bone tracer cardiac scintigraphy and cardiac magnetic resonance imaging have been established as first steps for its diagnosis. This study aimed to develop a deep learning model to support the diagnosis of cardiac amyloidosis from haematoxylin/eosin (HE)-stained myocardial tissue.

Methods And Results: This single-centre retrospective observational study enrolled 166 patients who underwent myocardial biopsies between 2008 and 2022, including 76 patients diagnosed with cardiac amyloidosis and 90 with other diagnoses.