Targeted deep brain stimulation of the motor thalamus improves speech and swallowing motor functions after cerebral lesions.

Speech and swallowing are complex motor acts that depend upon the integrity of input neural signals from motor cortical areas to control muscles of the head and neck. Lesions damaging these neural pathways result in weakness of key muscles causing dysarthria and dysphagia, leading to profound social isolation and risk of aspiration and suffocation. Here we show that Deep Brain Stimulation (DBS) of the motor thalamus improved speech and swallowing functions in two participants with dysarthria and dysphagia.

Uncovering the hidden effects of repetitive subconcussive head impact exposure: A mega-analytic approach characterizing seasonal brain microstructural changes in contact and collision sports athletes.

Repetitive subconcussive head impacts (RSHI) are believed to induce sub-clinical brain injuries, potentially resulting in cumulative, long-term brain alterations. This study explores patterns of longitudinal brain white matter changes across sports with RSHI-exposure. A systematic literature search identified 22 datasets with longitudinal diffusion magnetic resonance imaging data.

DNA fork remodeling proteins, Zranb3 and Smarcal1, are uniquely essential for aging hematopoiesis.

Over a lifetime, hematopoietic stem and progenitor cells (HSPCs) are forced to repeatedly proliferate to maintain hematopoiesis, increasing their susceptibility to DNA damaging replication stress. However, the proteins that mitigate this stress, protect HSPC replication, and prevent aging-driven dysregulation are unknown. We report two evolutionarily conserved, ubiquitously expressed chromatin remodeling enzymes with similar DNA replication fork reversal biochemical functions, Zranb3 and Smarcal1, have surprisingly specialized roles in distinct HSPC populations.

Respiratory Syncytial Virus-Associated Hospitalizations in Children <5 Years: 2016-2022.

Background: The coronavirus disease 2019 pandemic disrupted respiratory syncytial virus (RSV) seasonality resulting in early, atypical RSV seasons in 2021 and 2022, with an intense 2022 peak overwhelming many pediatric healthcare facilities.

Methods: We conducted prospective surveillance for acute respiratory illness during 2016-2022 at 7 pediatric hospitals. We interviewed parents, reviewed medical records, and tested respiratory specimens for RSV and other respiratory viruses.

Strain concentration drives the anatomical distribution of injury in acute and chronic traumatic brain injury.

Brain tissue injury caused by mild traumatic brain injury (mTBI) disproportionately concentrates in the midbrain, cerebellum, mesial temporal lobe, and the interface between cortex and white matter at sulcal depths . The bio-mechanical principles that explain why physical impacts to different parts of the skull translate to common foci of injury concentrated in specific brain structures are unknown. A general and longstanding idea, which has not to date been directly tested in humans, is that different brain regions are differentially susceptible to strain loading.

Facilitating knowledge transfer to policy makers and front-line workers during a pandemic: Implementation, impact and lessons learned.

Background: Stakeholders working on the COVID-19 pandemic response needed access to evidence, requiring a systematic approach to identify and disseminate relevant research.

Objectives: Outline the stages of development of a COVID-19 Literature Digest; demonstrate the impact the Digest had on decision-making and knowledge gain; identify the lessons learned.

Methods: A standardised process was developed to identify and select papers.

Reciprocal interactions among parietal and occipito-temporal representations support everyday object-directed actions.

Everyday interactions with common manipulable objects require the integration of conceptual knowledge about objects and actions with real-time sensory information about the position, orientation and volumetric structure of the grasp target. The ability to successfully interact with everyday objects involves analysis of visual form and shape, surface texture, material properties, conceptual attributes such as identity, function and typical context, and visuomotor processing supporting hand transport, grasp form, and object manipulation. Functionally separable brain regions across the dorsal and ventral visual pathways support the processing of these different object properties and, in cohort, are necessary for functional object use.

EUS-guided thrombin injection and coil implantation for gastric varices: feasibility, safety, and outcomes.

Background And Aims: Gastric varices (GVs) are reported in up to 20% of patients with portal hypertension, and bleeding is often more severe and challenging than esophageal variceal bleeding. Data are limited on prophylaxis of GV bleeding or management in the acute setting, and different techniques are used. This study evaluated outcomes after EUS-guided placement of coils in combination with thrombin to manage GVs.

Conformational states of the microtubule nucleator, the γ-tubulin ring complex.

Microtubules (MTs) perform essential functions in the cell, and it is critical that they are made at the correct cellular location and cell cycle stage. This nucleation process is catalyzed by the γ-tubulin ring complex (γ-TuRC), a cone-shaped protein complex composed of over 30 subunits. Despite recent insight into the structure of vertebrate γ-TuRC, which shows that its diameter is wider than that of a MT, and that it exhibits little of the symmetry expected for an ideal MT template, the question of how γ-TuRC achieves MT nucleation remains open.

Comparative genomic analysis of PIK3R1-mutated and wild-type breast cancers.

Purpose: The PIK3R1 gene encodes the regulatory subunit-p85a-of the PI3K signaling complex. Prior studies have found that pathogenic somatic alterations in PIK3R1 are enriched in human breast cancers but the genomic landscape of breast cancer patients harboring PIK3R1 mutations has not been extensively characterized.

Methods: We retrospectively analyzed 6,009 patient records that underwent next-generation sequencing (NGS) using the Tempus xT solid tumor assay.

Technical and clinical outcomes following EUS-guided thrombin injection and coil implantation for parastomal varices.

Background And Aims: Bleeding from parastomal varices causes significant morbidity and mortality. Treatment options are limited, particularly in high-risk patients with significant underlying liver disease and other comorbidities. The use of EUS-guided embolisation coils combined with thrombin injection in gastric varices has been shown to be safe and effective.

Spatial determination and prognostic impact of the fibroblast transcriptome in pancreatic ductal adenocarcinoma.

Pancreatic ductal adenocarcinoma has a poor clinical outcome and responses to immunotherapy are suboptimal. Stromal fibroblasts are a dominant but heterogenous population within the tumor microenvironment and therapeutic targeting of stromal subsets may have therapeutic utility. Here, we combine spatial transcriptomics and scRNA-Seq datasets to define the transcriptome of tumor-proximal and tumor-distal cancer-associated fibroblasts (CAFs) and link this to clinical outcome.

Meaningful coproduction with clinicians: establishing a practice-based research network with physiotherapists in regional Australia.

Background: The disconnect between research and clinical practice leads to research evidence that is often not useful for clinical practice. Practice-based research networks are collaborations between researchers and clinicians aimed at coproducing more useful research. Such networks are rare in the physiotherapy field.

COVID-19 Surveillance After Expiration of the Public Health Emergency Declaration - United States, May 11, 2023.

On January 31, 2020, the U.S. Department of Health and Human Services (HHS) declared, under Section 319 of the Public Health Service Act, a U.

Integrated model of the vertebrate augmin complex.

Accurate segregation of chromosomes is required to maintain genome integrity during cell division. This feat is accomplished by the microtubule-based spindle. To build a spindle rapidly and with high fidelity, cells take advantage of branching microtubule nucleation, which rapidly amplifies microtubules during cell division.

Partnering with patients and families living with chronic conditions to coproduce diagnostic safety through OurDX: a previsit online engagement tool.

Objective: Patients and families are key partners in diagnosis, but methods to routinely engage them in diagnostic safety are lacking. Policy mandating patient access to electronic health information presents new opportunities. We tested a new online tool ("OurDX") that was codesigned with patients and families, to determine the types and frequencies of potential safety issues identified by patients/families with chronic health conditions and whether their contributions were integrated into the visit note.

Tissue-Resident Memory T Cells in Pancreatic Ductal Adenocarcinoma Coexpress PD-1 and TIGIT and Functional Inhibition Is Reversible by Dual Antibody Blockade.

Pancreatic ductal adenocarcinoma (PDAC) has a poor clinical outlook. Responses to immune checkpoint blockade are suboptimal and a much more detailed understanding of the tumor immune microenvironment is needed if this situation is to be improved. Here, we characterized tumor-infiltrating T-cell populations in patients with PDAC using cytometry by time of flight (CyTOF) and single-cell RNA sequencing.