Transscleral Pars Plana Choroid Ablation Using the Iridex Laser System Yields Improvements for Surgical Insertion of the Port Delivery Implant in a Minipig Model.

Purpose: To evaluate an alternative surgical approach for Port Delivery System with ranibizumab (PDS) implant and a novel application of Iridex laser system in Gottingen minipig model.

Methods: A total of seventeen male minipigs (Part 1: 9 animals in non-recovery and Part 2: 8 animals observed for 8-days post-surgery Part 2) received PDS implant insertion into each eye. The effect of Iridex 810 nm infrared diode laser with varying energy (power or duration) on transscleral pars plana ablation, surrounding ocular tissue and postsurgical vitreous hemorrhage (VH) was investigated.

Abundant and active community members respond to diel cycles in hot spring phototrophic mats.

Photosynthetic microbial mats in hot springs can provide insights into the diel behaviors of communities in extreme environments. In this habitat, photosynthesis dominates during the day, leading to super-oxic conditions, with a rapid transition to fermentation and anoxia at night. Multiple samples were collected from two springs over several years to generate metagenomic and metatranscriptomic datasets.

Quantifying the Detection Sensitivity and Precision of qPCR and ddPCR Mechanisms for eDNA Samples.

Environmental DNA (eDNA) detection employing quantitative PCR (qPCR) and droplet digital PCR (ddPCR) offers a non-invasive and efficient approach for monitoring aquatic organisms. Accurate and sensitive quantification of eDNA is crucial for tracking rare and invasive species and understanding the biodiversity abundance and distribution of aquatic organisms. This study compares the sensitivity and quantification precision of qPCR and ddPCR for eDNA surveys through Bayesian inference using latent parameters from both known concentration (standards) and environmental samples across three teleost fish species assays.

Questionnaires of self-perception poorly correlate with instability elicited by walking balance perturbations.

Rehabilitation to prevent falls should not only directly address intrinsic and extrinsic factors, but also the neuropsychology of falls to promote safe and independent mobility in our aging population. The purpose of this study was to determine the relation between falls self-efficacy and objective responses to a series of walking balance perturbations. 29 healthy younger adults and 28 older adults completed four experimental trials, including unperturbed walking and walking while responding to three perturbations: mediolateral optical flow, treadmill-induced slips, and lateral waist-pulls; and three self-reported questionnaires: Activity-specific Balance Confidence, Falls Efficacy Scale, and the Fear of Falling Questionnaire-Revised.

IN VIVO CELL-TYPE AND BRAIN REGION CLASSIFICATION VIA MULTIMODAL CONTRASTIVE LEARNING.

Current electrophysiological approaches can track the activity of many neurons, yet it is usually unknown which cell-types or brain areas are being recorded without further molecular or histological analysis. Developing accurate and scalable algorithms for identifying the cell-type and brain region of recorded neurons is thus crucial for improving our understanding of neural computation. In this work, we develop a multimodal contrastive learning approach for neural data that can be fine-tuned for different downstream tasks, including inference of cell-type and brain location.

Pilot Study: Behavioral and Medical Clinical Partnership for Optimization of Positive Airway Pressure Therapy in Pediatric Patients.

Background: To assess the effectiveness of a structured algorithm for pediatric positive airway pressure (PAP) initiation for the treatment of obstructive sleep apnea (OSA).

Methods: An algorithm was created to support pediatric PAP use and identify patients who could benefit from early behavioral consultation and education. Sleep providers implemented a unified introduction to PAP therapy with the PAP therapy toolkit.

A clinical-translational review of sleep problems in neurodevelopmental disabilities.

Sleep disorders are very common across neurodevelopmental disorders and place a large burden on affected children, adolescents, and their families. Sleep disturbances seem to involve a complex interplay of genetic, neurobiological, and medical/environmental factors in neurodevelopmental disorders. In this review, we discuss animal models of sleep problems and characterize their presence in two single gene disorders, Rett Syndrome, and Angelman Syndrome and two more commonly occurring neurodevelopmental disorders, Down Syndrome, and autism spectrum disorders.

Combination of dual JAK/HDAC inhibitor with regorafenib synergistically reduces tumor growth, metastasis, and regorafenib-induced toxicity in colorectal cancer.

Background: Treatment with regorafenib, a multiple-kinase inhibitor, to manage metastatic colorectal cancers (mCRCs) shows a modest improvement in overall survival but is associated with severe toxicities. Thus, to reduce regorafenib-induced toxicity, we used regorafenib at low concentration along with a dual JAK/HDAC small-molecule inhibitor (JAK/HDACi) to leverage the advantages of both JAK and HDAC inhibition to enhance antitumor activity. The therapeutic efficacy and safety of the combination treatment was evaluated with CRC models.

Advancing clinical trial equity through integration of telehealth and decentralized treatment.

Innovative strategies to increase clinical trial accessibility and equity are needed. We conducted a retrospective review of a phase II investigator-initiated trial to determine whether the modification of clinical trial design to decentralize study treatment can improve trial accessibility among underrepresented groups. Sociodemographic characteristics, including area deprivation indices, as well as study site travel distance, time, and costs were compared between enrolled participants who received chemotherapy locally and participants who did not.

Translational PK/PD and the first-in-human dose selection of a PD1/IL15: an engineered recombinant targeted cytokine for cancer immunotherapy.

Introduction: Interleukin 15 (IL-15) is a potential anticancer agent and numerous engineered IL-15 agonists are currently under clinical investigation. Selective targeting of IL-15 to specific lymphocytes may enhance therapeutic effects while helping to minimize toxicities.

Methods: We designed and built a heterodimeric targeted cytokine (TaCk) that consists of an anti-programmed cell death 1 receptor antibody (anti-PD-1) and an engineered IL-15.

The effects of plantarflexor weakness and reduced tendon stiffness with aging on gait stability.

Falls among older adults are a costly public health concern. Such falls can be precipitated by balance disturbances, after which a recovery strategy requiring rapid, high force outputs is necessary. Sarcopenia among older adults likely diminishes their ability to produce the forces necessary to arrest gait instability.

Trans-lesion synthesis and mismatch repair pathway crosstalk defines chemoresistance and hypermutation mechanisms in glioblastoma.

Almost all Glioblastoma (GBM) are either intrinsically resistant to the chemotherapeutical drug temozolomide (TMZ) or acquire therapy-induced mutations that cause chemoresistance and recurrence. The genome maintenance mechanisms responsible for GBM chemoresistance and hypermutation are unknown. We show that the E3 ubiquitin ligase RAD18 (a proximal regulator of TLS) is activated in a Mismatch repair (MMR)-dependent manner in TMZ-treated GBM cells, promoting post-replicative gap-filling and survival.

The dementia care study (D-CARE): Recruitment strategies and demographic characteristics of participants in a pragmatic randomized trial of dementia care.

Introduction: Pragmatic research studies that include diverse dyads of persons living with dementia (PLWD) and their family caregivers are rare.

Methods: Community-dwelling dyads were recruited for a pragmatic clinical trial evaluating three approaches to dementia care. Four clinical trial sites used shared and site-specific recruitment strategies to enroll health system patients.

Draft genome of s sp. MS-CIW-1, of the sp. MS-G group from Mushroom Spring, Yellowstone National Park.

sp. MS-CIW-1 was isolated from a phototrophic mat in Mushroom Spring, an alkaline hot spring in Yellowstone National Park, WY, USA. We report the draft genome of 4.

Prejudicial findings regarding suitability for intended purpose during pre-purchase examinations in a mixed horse population-A retrospective observational study in the United Kingdom.

Background: Pre-purchase examinations (PPEs) are performed for prospective purchasers of horses to identify prejudicial findings that could make animals unsuitable for an intended use. Although this examination process is often standardised, PPEs remain, in large parts, a subjective procedure. In the United Kingdom, PPEs generally consist of either a two stage (two stage vetting [2SV], i.

Modeling ocean distributions and abundances of natural- and hatchery-origin Chinook salmon stocks with integrated genetic and tagging data.

Background: Considerable resources are spent to track fish movement in marine environments, often with the intent of estimating behavior, distribution, and abundance. Resulting data from these monitoring efforts, including tagging studies and genetic sampling, often can be siloed. For Pacific salmon in the Northeast Pacific Ocean, predominant data sources for fish monitoring are coded wire tags (CWTs) and genetic stock identification (GSI).

Does the effect of walking balance perturbations generalize across contexts?

Balance perturbations are used to study locomotor instability. However, these perturbations are designed to provoke a specific context of instability that may or may not generalize to a broader understanding of falls risk. The purpose of this study was to determine if the effect of balance perturbations on instability generalizes across contexts.

Trans-Lesion Synthesis and Mismatch Repair Pathway Crosstalk Defines Chemoresistance and Hypermutation Mechanisms in Glioblastoma.

Almost all Glioblastoma (GBM) are either intrinsically resistant to the chemotherapeutical drug temozolomide (TMZ) or acquire therapy-induced mutations that cause chemoresistance and recurrence. The genome maintenance mechanisms responsible for GBM chemoresistance and hypermutation are unknown. We show that the E3 ubiquitin ligase RAD18 (a proximal regulator of TLS) is activated in a Mismatch repair (MMR)-dependent manner in TMZ-treated GBM cells, promoting post-replicative gap-filling and survival.

Trans-Lesion Synthesis and Mismatch Repair Pathway Crosstalk Defines Chemoresistance and Hypermutation Mechanisms in Glioblastoma.

Almost all Glioblastoma (GBM) are either intrinsically resistant to the chemotherapeutical drug temozolomide (TMZ) or acquire therapy-induced mutations that cause chemoresistance and recurrence. The genome maintenance mechanisms responsible for GBM chemoresistance and hypermutation are unknown. We show that the E3 ubiquitin ligase RAD18 (a proximal regulator of TLS) is activated in a Mismatch repair (MMR)-dependent manner in TMZ-treated GBM cells, promoting post-replicative gap-filling and survival.

A multifaceted architectural framework of the mouse claustrum complex.

Accurate anatomical characterizations are necessary to investigate neural circuitry on a fine scale, but for the rodent claustrum complex (CLCX), this has yet to be fully accomplished. The CLCX is generally considered to comprise two major subdivisions, the claustrum (CL) and the dorsal endopiriform nucleus (DEn), but regional boundaries to these areas are debated. To address this, we conducted a multifaceted analysis of fiber- and cytoarchitecture, genetic marker expression, and connectivity using mice of both sexes, to create a comprehensive guide for identifying and delineating borders to CLCX, including an online reference atlas.

Glioma Stem Cells Are Sensitized to BCL-2 Family Inhibition by Compromising Histone Deacetylases.

Glioblastoma (GBM) remains an incurable disease with an extremely high five-year recurrence rate. We studied apoptosis in glioma stem cells (GSCs) in response to HDAC inhibition (HDACi) combined with MEK1/2 inhibition (MEKi) or BCL-2 family inhibitors. MEKi effectively combined with HDACi to suppress growth, induce cell cycle defects, and apoptosis, as well as to rescue the expression of the pro-apoptotic BH3-only proteins BIM and BMF.

Ultra-high density electrodes improve detection, yield, and cell type identification in neuronal recordings.

To understand the neural basis of behavior, it is essential to sensitively and accurately measure neural activity at single neuron and single spike resolution. Extracellular electrophysiology delivers this, but it has biases in the neurons it detects and it imperfectly resolves their action potentials. To minimize these limitations, we developed a silicon probe with much smaller and denser recording sites than previous designs, called Neuropixels Ultra ().