Association between DNA damage repair alterations and outcomes to Lu-PSMA-617 in advanced prostate cancer.

Background: Lu-prostate-specific membrane antigen (PSMA)-617 (LuPSMA) is a radionuclide therapy approved for patients with PSMA-avid metastatic castrate-resistant prostate cancer (mCRPC). We evaluated whether alterations in the DNA damage repair (DDR) pathway were associated with outcomes to LuPSMA.

Patients And Methods: We identified an institutional cohort of men (n = 134) treated with ≥2 cycles of LuPSMA who had panel-based germline and/or tumor genomic sequencing.

Structural and functional analysis of the Nipah virus polymerase complex.

Nipah virus (NiV) is a bat-borne, zoonotic RNA virus that is highly pathogenic in humans. The NiV polymerase, which mediates viral genome replication and mRNA transcription, is a promising drug target. We determined the cryoelectron microscopy (cryo-EM) structure of the NiV polymerase complex, comprising the large protein (L) and phosphoprotein (P), and performed structural, biophysical, and in-depth functional analyses of the NiV polymerase.

Spontaneous oxycodone withdrawal disrupts sleep, diurnal, and electrophysiological dynamics in rats.

Opioid dependence is defined by an aversive withdrawal syndrome upon drug cessation that can motivate continued drug-taking, development of opioid use disorder, and precipitate relapse. An understudied but common opioid withdrawal symptom is disrupted sleep, reported as both insomnia and daytime sleepiness. Despite the prevalence and severity of sleep disturbances during opioid withdrawal, there is a gap in our understanding of their interactions.

Cementless fixation in total joint arthroplasty: Factors impacting osseointegration.

•The success of cementless fixation in TJA depends on a multitude of factors including biological, mechanical, implant, surgical, and material properties.•Biologic fixation has become the primary mode of fixation for the majority of primary total hip arthroplasty (THA) surgeries done today in the United States (US) due to its low complication rate and superior longevity compared to cemented fixation.•Cementless fixation has yet to gain wider acceptance in total knee arthroplasty (TKA) and hip hemiarthroplasty due to several factors including host bone quality, implant design, and surgical technique.

In vivo calcium imaging reveals directional sensitivity of C-low threshold mechanoreceptors.

C-low threshold mechanoreceptors (C-LTMRs) in animals (termed C-tactile (CT) fibres in humans) are a subgroup of C-fibre primary afferents, which innervate hairy skin and respond to low-threshold punctate indentations and brush stimuli. These afferents respond to gentle touch stimuli and are implicated in mediating pleasant/affective touch. These afferents have traditionally been studied using low-throughput, technically challenging approaches, including microneurography in humans and teased fibre electrophysiology in other mammals.

Reverse transcriptase inhibitors diminish systemic proinflammatory responses to bacterial pathogens.

Bacterial infections can induce exuberant immune responses that can damage host tissues. Previously, we demonstrated that systemic infection in mice causes tissue damage in the liver. This liver necrosis is associated with the expression of endogenous retroviruses, chromosomally integrated retroviruses that encode a reverse transcriptase.

Molecular basis for shifted receptor recognition by an encephalitic arbovirus.

After decades of inactivity throughout the Americas, western equine encephalitis virus (WEEV) recently re-emerged in South America, causing a large-scale outbreak in humans and horses. WEEV binds protocadherin 10 (PCDH10) as a receptor; however, nonpathogenic strains no longer bind human or equine PCDH10 but retain the ability to bind avian receptors. Highly virulent WEEV strains can also bind the very low-density lipoprotein receptor (VLDLR) and apolipoprotein E receptor 2 (ApoER2) as alternative receptors.

Clinical Problem Solving: Two Patients With Gait Instability and Difficulty With Hand Coordination.

Subacute-to-chronic gait instability has a broad differential diagnosis. The neurological exam can help elucidate the localization and suggest an underlying etiology of the symptomatology, which can lead to a more focused diagnostic approach. Two patients are described - 1 with a month of worsening difficulty with ambulation that evolved to bilateral hand discoordination and another with 18 months of progressive difficulty with ambulation that also then progressed to involve her bilateral hands.

Sleep macro-architecture and dementia risk in adults: Meta-analysis of 5 cohorts from the Sleep and Dementia Consortium.

Study Objectives: Poor sleep may play a role in the risk of dementia. However, few studies have investigated the association between polysomnography (PSG)-derived sleep architecture and dementia incidence. We examined the relationship between sleep macro-architecture and dementia incidence across five US-based cohort studies from the Sleep and Dementia Consortium (SDC).

Joint Associations of Sedentary Time and Intensity-Specific Physical Activity With Cancer Mortality: A Device-Based Cohort Study of 72,458 UK Adults.

Background: There are no studies examining the prospective joint association of device-based measures of sedentary time and physical activity (PA) with cancer mortality. We examined the joint associations of sedentary time and intensity-specific PA with cancer mortality in 72,458 adults from UK Biobank.

Methods: Participants wore an Axivity AX3 accelerometer on their dominant wrist for at least 3 days (with at least 1 weekend day).

WS/MHS PdTe/Si Mixed-Dimensional Heterojunction as Ultra-Broadband Photodetector for Health and Safety Monitoring.

Ultra-broadband photodetectors (UB-PDs) are essential in medical applications, public safety monitoring, and various other fields. However, developing UB-PDs covering multiple bands from ultraviolet to medium infrared remains a challenge due to material limitations. Here, a mixed-dimensional heterojunction composed of 2D WS/monodisperse hexagonal stacking (MHS) 3D PdTe particles on 3D Si is proposed, capable of detecting light from 365 to 9600 nm.

Host-microbe multiomic profiling identifies distinct COVID-19 immune dysregulation in solid organ transplant recipients.

Coronavirus disease 2019 (COVID-19) poses significant risks for solid organ transplant recipients, who have atypical but poorly characterized immune responses to infection. We aim to understand the host immunologic and microbial features of COVID-19 in transplant recipients by leveraging a prospective multicenter cohort of 86 transplant recipients age- and sex-matched with 172 non-transplant controls. We find that transplant recipients have higher nasal SARS-CoV-2 viral abundance and impaired viral clearance, and lower anti-spike IgG levels.

Use of Financial Hardship as a Metric for Assessing Financial Toxicity in Surgical Trauma Patients.

Background: Financial toxicity is the detrimental impact of health care costs that must be mitigated to achieve universal health coverage. Catastrophic health expenditure (CHE) is widely used to measure financial toxicity but does not capture patient perspectives of unaffordable health care costs. Financial hardship (FH), a patient-reported outcome measure, is currently underutilized but may be an important adjunct metric.

Gene signatures derived from transcriptomic-causal networks stratify colorectal cancer patients for effective targeted therapy.

Background: Gene signatures derived from transcriptomic-causal networks offer potential for tailoring clinical care in cancer treatment by identifying predictive and prognostic biomarkers. This study aimed to uncover such signatures in metastatic colorectal cancer (CRC) patients to aid treatment decisions.

Methods: We constructed transcriptomic-causal networks and integrated gene interconnectivity into overall survival (OS) analysis to control for confounding genes.

Evaluating an ICD-10 Based Proxy for Date of Birth in Electronic Health Record Data.

Purpose: To comply with the Health Insurance Portability and Accountability Act of 1996 (HIPAA) Privacy Rule, many real-world data providers mask a patient's date of birth by supplying only year of birth to data users. The lack of granularity around patient age is a challenge when using RWD, especially for pediatric research studies. In this study, a proxy for patient date of birth is evaluated using electronic health record (EHR) data.

Synthesis and Characterization of a Nanoclay Reinforced Gelatin-Based Hybrid Hydrogel.

Bentonite clay nanoparticles assume a pivotal role in 3D bioprinting and tissue engineering by augmenting the mechanical rigidity and biological efficacy of hydrogels. In this investigation, Span80 was employed as a surfactant to facilitate the synthesis of uniformly sized bentonite nanoparticles measuring approximately 700 nm in diameter. The resultant hybrid hydrogel displaced a marked increase in compressive modulus, achieving a peak value of 17.

Engaging dystonia networks with subthalamic stimulation.

Deep brain stimulation is an efficacious treatment for dystonia. While the internal pallidum serves as the primary target, recently, stimulation of the subthalamic nucleus (STN) has been investigated. However, optimal targeting within this structure and its surroundings have not been studied in depth.

Comparison of PREMM5 and PREMMplus Risk Assessment Models to Identify Lynch Syndrome.

Purpose: Clinical risk assessment models can identify patients with hereditary cancer susceptibility, but it is unknown how multigene cancer syndrome prediction models compare with syndrome-specific models in assessing risk for individual syndromes such as Lynch syndrome (LS). Our aim was to compare PREMMplus (a 19-gene cancer risk prediction model) with PREMM5 (a LS gene-specific model) for LS identification.

Methods: We analyzed data from two cohorts of patients undergoing germline testing from a commercial laboratory (n = 12,020) and genetics clinic (n = 6,232) with personal and/or family histories of LS-associated cancer.

High prevalence of reverse transcriptase inhibitors associated resistance mutations among people living with HIV on dolutegravir-based antiretroviral therapy in Francistown, Botswana.

Objectives: We assessed HIV-1 drug resistance profiles among people living with HIV (PLWH) with detectable viral load (VL) and on dolutegravir-based antiretroviral therapy (ART) in Botswana.

Methods: The study utilised available 100 residual HIV-1 VL samples from unique PLWH in Francistown who had viraemia at-least 6 months after initiating ART in Botswana's national ART program from November 2023 to January 2024. Viraemia was categorized as low-level viraemia (LLV) (VL: 200-999 copies/mL) or virologic failure (VF) (VL ≥1000 copies/mL).