Multicenter Expanded Access Protocol for Research Through Access to Trehalose in People With Amyotrophic Lateral Sclerosis.

Introduction/aims: Expanded access protocols (EAPs) allow individuals ineligible for clinical trials to receive investigational products. EAP data can be collected in parallel to randomized clinical trials (RCTs) and serve as a source of evidence in clinical practice. Here, we present the results of a National Institutes of Health (NIH)-funded EAP for amyotrophic lateral sclerosis (ALS).

Stable two-year longitudinal clinical outcomes in LRRK2 G2019S non-manifest carriers in a remote nationwide study.

Background: Interest in Parkinson's disease (PD) prevention trials is growing, and genetically at-risk individuals may be ideal candidates. LRRK2 G2019S is the most common autosomal dominant genetic cause of PD and exhibits incomplete penetrance.

Objective: In a remote, prospective cohort study of LRRK2 G2019S carriers without PD, we examined change over time to better understand the natural history of LRRK2 PD.

Mapping Macaque to Human Cortex with Natural Scene Responses.

Neuroscience has long relied on macaque studies to infer human brain function, yet identifying functionally corresponding brain regions across species and measurement modalities remains a fundamental challenge. This is especially true for higher-order cortex, where functional interpretations are constrained by narrow hypotheses and anatomical landmarks are often non-homologous. We present a data-driven approach for mapping functional correspondence across species using rich, naturalistic stimuli.

Probing into Intraband Transitions Enabled Charge Carrier Dynamics of THz Response Generated in Graphene/MoS Heterostructures.

The engineering of terahertz phonons is challenging due to difficulties in achieving sub-nanometer material precision and in facilitating efficient phonon coupling at terahertz frequencies region. The effective generation, detection, and manipulation of terahertz phonons via the integration of atomically thin layers in van der Waals heterostructures can enable new designs for next-generation optoelectronic quantum devices, offering new avenues for thermal engineering in the terahertz regime. Here, optical pump terahertz probe and terahertz time-domain experiments are used to reveal the behavior of charge carrier transfer in real time at heterostructure interfaces of single-layer graphene and monolayer MoS upon photoexcitation and plausible mechanism has been put forward.

Structural visualization of small molecule recognition by CXCR3 uncovers dual-agonism in the CXCR3-CXCR7 system.

Chemokine receptors are critically involved in multiple physiological and pathophysiological processes related to immune response mechanisms. Most chemokine receptors are prototypical GPCRs although some also exhibit naturally-encoded signaling-bias toward β-arrestins (βarrs). C-X-C type chemokine receptors, namely CXCR3 and CXCR7, constitute a pair wherein the former is a prototypical GPCR while the latter exhibits selective coupling to βarrs despite sharing a common natural agonist: CXCL11.

A Multisite Demonstration of Shared Access to Older Adults' Patient Portals.

Importance: The patient portal has a growing role in health care. Many health systems have implemented shared access functionality in which patients may register a care partner with unique identity credentials to access their portal. Uptake of shared access has been limited.

Molecular basis of promiscuous chemokine binding and structural mimicry at the C-X-C chemokine receptor, CXCR2.

Selectivity of natural agonists for their cognate receptors is a hallmark of G-protein-coupled receptors (GPCRs); however, this selectivity often breaks down at the chemokine receptors. Chemokines often display promiscuous binding to chemokine receptors, but the underlying molecular determinants remain mostly elusive. Here, we perform a comprehensive transducer-coupling analysis, testing all known C-X-C chemokines on every C-X-C type chemokine receptor to generate a global fingerprint of the selectivity and promiscuity encoded within this system.

Return of individual research results to participants with and at risk for Parkinson's disease.

In a prospective, remote natural history study of 277 individuals with (60) and genetically at risk for (217) Parkinson's disease (PD), we examined interest in the return of individual research results (IRRs) and compared characteristics of those who opted for versus against the return of IRRs. Most ( = 180, 65%) requested sharing of IRRs with either a primary care provider, neurologist, or themselves. Among individuals without PD, those who requested sharing of IRRs with a clinician reported more motor symptoms than those who did not request any sharing (mean (SD) 2.

Face cells encode object parts more than facial configuration of illusory faces.

Humans perceive illusory faces in everyday objects with a face-like configuration, an illusion known as face pareidolia. Face-selective regions in humans and monkeys, believed to underlie face perception, have been shown to respond to face pareidolia images. Here, we investigated whether pareidolia selectivity in macaque inferotemporal cortex is explained by the face-like configuration that drives the human perception of illusory faces.

Molecular mechanism of distinct chemokine engagement and functional divergence of the human Duffy antigen receptor.

The Duffy antigen receptor is a seven-transmembrane (7TM) protein expressed primarily at the surface of red blood cells and displays strikingly promiscuous binding to multiple inflammatory and homeostatic chemokines. It serves as the basis of the Duffy blood group system in humans and also acts as the primary attachment site for malarial parasite Plasmodium vivax and pore-forming toxins secreted by Staphylococcus aureus. Here, we comprehensively profile transducer coupling of this receptor, discover potential non-canonical signaling pathways, and determine the cryoelectron microscopy (cryo-EM) structure in complex with the chemokine CCL7.

Barriers to participation in clinical trials of rural older adult cancer survivors: A qualitative study.

Background: Currently, 64% of cancer survivors are aged 65+. Older cancer survivors have unique complications after chemotherapy and are often excluded from cancer clinical trials. Although there is research on barriers to clinical trial participation of older adult cancer survivors, to date no research has explored barriers to clinical trial participation unique to rural older adult cancer survivors.

Feature-selective responses in macaque visual cortex follow eye movements during natural vision.

In natural vision, primates actively move their eyes several times per second via saccades. It remains unclear whether, during this active looking, visual neurons exhibit classical retinotopic properties, anticipate gaze shifts or mirror the stable quality of perception, especially in complex natural scenes. Here, we let 13 monkeys freely view thousands of natural images across 4.

Development and Evaluation of a Multisource Approach to Extend Mortality Follow-Up for Older Adults With Advanced Cancer Enrolled in Randomized Trials.

Purpose: Mortality data can complement primary end points from cancer clinical trials. Yet, identifying deaths after trial completion is challenging, as timely and comprehensive vital status data are unavailable in the United States. We developed and evaluated a multisource approach to capture death data after clinical trial completion.

Structure-guided engineering of biased-agonism in the human niacin receptor via single amino acid substitution.

The Hydroxycarboxylic acid receptor 2 (HCA2), also known as the niacin receptor or GPR109A, is a prototypical GPCR that plays a central role in the inhibition of lipolytic and atherogenic activities. Its activation also results in vasodilation that is linked to the side-effect of flushing associated with dyslipidemia drugs such as niacin. GPR109A continues to be a target for developing potential therapeutics in dyslipidemia with minimized flushing response.

Polyacrylonitrile as a versatile matrix for gold nanoparticle-based SERS substrates.

As an effective and ultrasensitive molecule detection technique, surface-enhanced Raman spectroscopy (SERS) needs efficient and highly responsive substrates to further enhance its sensitivity and utility. In this work, the preparation and characterisation of polyacrylonitrile/gold nanoparticle (PAN/AuNPs) composite porous films have been described for SERS-based detection of methylene blue (MB) dye. The PAN/AuNPs composite films were prepared with a simple dip coating technique, yielding a highly porous structure with uniformly dispersed Au nanoparticles (AuNPs).

Intrinsic functional clustering of the macaque insular cortex.

The functional organization of the primate insula has been studied using a variety of techniques focussing on regional differences in either architecture, connectivity, or function. These complementary methods offered insights into the complex organization of the insula and proposed distinct parcellation schemes at varying levels of detail and complexity. The advent of imaging techniques that allow non-invasive assessment of structural and functional connectivity, has popularized data-driven connectivity-based parcellation methods to investigate the organization of the human insula.

No Evidence for Cross-Modal fMRI Adaptation in Macaque Parieto-Premotor Mirror Neuron Regions.

To probe the presence of mirror neurons in the human brain, cross-modal fMRI adaptation has been suggested as a suitable technique. The rationale behind this suggestion is that this technique allows making more accurate inferences about neural response properties underlying fMRI voxel activations, beyond merely showing shared voxels that are active during both action observation and execution. However, the validity of using cross-modal fMRI adaptation to demonstrate the presence of mirror neurons in parietal and premotor brain regions has been questioned given the inconsistent and weak results obtained in human studies.

When the whole is only the parts: non-holistic object parts predominate face-cell responses to illusory faces.

Humans are inclined to perceive faces in everyday objects with a face-like configuration. This illusion, known as face pareidolia, is often attributed to a specialized network of 'face cells' in primates. We found that face cells in macaque inferotemporal cortex responded selectively to pareidolia images, but this selectivity did not require a holistic, face-like configuration, nor did it encode human faceness ratings.

Cancer survivorship challenges of rural older adults: a qualitative study.

Background: Although research has advanced the field of oncologic geriatrics with survivors to assess their cancer-related needs and devise patient-centered interventions, most of that research has excluded rural populations. This study aimed to understand the survivorship challenges and recommendations in the perspective of rural older adults.

Methods: This was a qualitative study that explored the survivorship challenges and recommendations of rural older adults who have completed curative intent chemotherapy for a solid tumor malignancy in the 12 months prior to enrollment in the present study.

Correction: study of the electronic states of VSi in momentum space.

[This corrects the article DOI: 10.1039/D3RA04535H.].