Inactivation of cytidine triphosphate synthase 1 prevents fatal auto-immunity in mice.

De novo synthesis of the pyrimidine, cytidine triphosphate (CTP), is crucial for DNA/RNA metabolism and depends on the CTP synthetases, CTPS1 and -2. Partial CTPS1 deficiency in humans has previously been shown to lead to immunodeficiency, with impaired expansion of T and B cells. Here, we examine the effects of conditional and inducible inactivation of Ctps1 and/or Ctps2 on mouse embryonic development and immunity.

Robot-assisted laparoscopic nephrectomy: early outcome measures with the implementation of multimodal analgesia and intrathecal morphine via the acute pain service.

Purpose: The objective of this study was to perform a retrospective cohort analysis, in which we measured the association of an acute pain service (APS)-driven multimodal analgesia protocol that included preoperative intrathecal morphine (ITM) compared to historic controls (i.e., surgeon-driven analgesia protocol without ITM) with postoperative opioid use.

Differences in Baseline Physical Function and Mental Health PROM Scores in Patients With Foot and Ankle Conditions.

Background: This study sought to establish normative values for baseline physical and mental health by foot and ankle diagnosis using validated PROMIS scores and to compare the correlation between these 2 outcomes across common diagnoses. Additionally, it investigated the effects associated with chronic vs acute conditions and specific diagnoses on mental health.

Methods: We reviewed baseline PROMIS Physical Function 10a (PF10a) and PROMIS Global-Mental (PGM) scores of 14,245 patients with one of the 10 most common foot and ankle diagnoses seen at our institution between 2016 and 2021.

Interim Estimates of 2023-24 Seasonal Influenza Vaccine Effectiveness - United States.

In the United States, annual influenza vaccination is recommended for all persons aged ≥6 months. Using data from four vaccine effectiveness (VE) networks during the 2023-24 influenza season, interim influenza VE was estimated among patients aged ≥6 months with acute respiratory illness-associated medical encounters using a test-negative case-control study design. Among children and adolescents aged 6 months-17 years, VE against influenza-associated outpatient visits ranged from 59% to 67% and against influenza-associated hospitalization ranged from 52% to 61%.

Prevention of life-threatening bleeding complication from splenic venous ectasia by B-mode-, color Doppler- and contrast-enhanced ultrasound in a patient with ALL.

Aim Of The Study: Spontaneous splenic rupture is a serious complication of pathologically altered spleen tissue, associated with a high mortality rate.

Case Description: We describe a spontaneous splenic rupture in a patient with acute lymphoblastic leukemia undergoing chemotherapy. Ultrasound revealed splenomegaly, and diffuse splenic acute lymphoblastic leukemia-infiltration was suspected.

ITRUSST Consensus on Standardised Reporting for Transcranial Ultrasound Stimulation.

As transcranial ultrasound stimulation (TUS) advances as a precise, non-invasive neuromodulatory method, there is a need for consistent reporting standards to enable comparison and reproducibility across studies. To this end, the International Transcranial Ultrasonic Stimulation Safety and Standards Consortium (ITRUSST) formed a subcommittee of experts across several domains to review and suggest standardised reporting parameters for low intensity TUS, resulting in the guide presented here. The scope of the guide is limited to reporting the ultrasound aspects of a study.

The DizzyQuest Combined with Accelerometry: Daily Physical Activities and Limitations among Patients with Bilateral Vestibulopathy Due to DFNA9.

Background: DFNA9 is a genetic disease of the inner ear, causing progressive bilateral sensorineural deafness and bilateral vestibulopathy (BV). In this study, DizzyQuest, a mobile vestibular diary, and the MOX accelerometer were combined to assess the daily life functional limitations and physical activity of patients with DFNA9 suffering from BV. These parameters might be appropriate as potential candidacy criteria and outcome measures for new therapeutic interventions for BV.

Primary Care Physician Preferences Regarding Communication from Orthopaedic Surgeons.

Background: Musculoskeletal consultations constitute a growing portion of primary care physician (PCP) referrals. Optimizing communication between PCPs and orthopaedists can potentially reduce time spent in the electronic medical record (EMR) as well as physician burnout. Little is known about the preferences of PCPs regarding communication from orthopaedic surgeons.

Supplemental oxygen requirement after tonsillectomy in children >3 years of age.

Introduction: The indications for postoperative admission after tonsillectomy in children >3 years of age are less well defined than for children <3 years old, and typically include severe obstructive sleep apnea (OSA), obesity, comorbidities, or behavioral factors. Inpatient care after tonsillectomy typically consists of respiratory monitoring and support, as respiratory compromise is the most common complication after pediatric tonsillectomy. We aim to evaluate risk factors associated with postoperative oxygen supplementation and to identify high risk populations within the admitted population who use additional resources or require additional interventions.

Face shape and motion are perceptually separable: Support for a revised model of face processing.

A recent model of face processing proposes that face shape and motion are processed in parallel brain pathways. Although tested in neuroimaging, the assumptions of this theory remain relatively untested through controlled psychophysical studies until now. Recruiting undergraduate students over the age of 18, we test this hypothesis using a tight control of stimulus factors, through computerized three-dimensional face models and calibration of dimensional discriminability, and of decisional factors, through a model-based analysis using general recognition theory (GRT).

A modular microfluidic platform to study how fluid shear stress alters estrogen receptor phenotype in ER breast cancer cells.

Metastatic breast cancer leads to poor prognoses and worse outcomes in patients due to its invasive behavior and poor response to therapy. It is still unclear what biophysical and biochemical factors drive this more aggressive phenotype in metastatic cancer; however recent studies have suggested that exposure to fluid shear stress in the vasculature could cause this. In this study a modular microfluidic platform capable of mimicking the magnitude of fluid shear stress (FSS) found in human vasculature was designed and fabricated.

Chromosome-level assembly of the gray fox (Urocyon cinereoargenteus) confirms the basal loss of PRDM9 in Canidae.

Reference genome assemblies have been created from multiple lineages within the Canidae family; however, despite its phylogenetic relevance as a basal genus within the clade, there is currently no reference genome for the gray fox (Urocyon cinereoargenteus). Here, we present a chromosome-level assembly for the gray fox (U. cinereoargenteus), which represents the most contiguous, non-domestic canid reference genome available to date, with 90% of the genome contained in just 34 scaffolds and a contig N50 and scaffold N50 of 59.

A retroviral link to vertebrate myelination through retrotransposon-RNA-mediated control of myelin gene expression.

Myelin, the insulating sheath that surrounds neuronal axons, is produced by oligodendrocytes in the central nervous system (CNS). This evolutionary innovation, which first appears in jawed vertebrates, enabled rapid transmission of nerve impulses, more complex brains, and greater morphological diversity. Here, we report that RNA-level expression of RNLTR12-int, a retrotransposon of retroviral origin, is essential for myelination.

A metabolic signature for NADSYN1-dependent congenital NAD deficiency disorder.

Nicotinamide adenine dinucleotide (NAD) is essential for embryonic development. To date, biallelic loss-of-function variants in 3 genes encoding nonredundant enzymes of the NAD de novo synthesis pathway - KYNU, HAAO, and NADSYN1 - have been identified in humans with congenital malformations defined as congenital NAD deficiency disorder (CNDD). Here, we identified 13 further individuals with biallelic NADSYN1 variants predicted to be damaging, and phenotypes ranging from multiple severe malformations to the complete absence of malformation.

Psychosis superspectrum II: neurobiology, treatment, and implications.

Alternatives to traditional categorical diagnoses have been proposed to improve the validity and utility of psychiatric nosology. This paper continues the companion review of an alternative model, the psychosis superspectrum of the Hierarchical Taxonomy of Psychopathology (HiTOP). The superspectrum model aims to describe psychosis-related psychopathology according to data on distributions and associations among signs and symptoms.

Experiences and impact of a rural Australian high-risk foot service: A multiple-methods study.

Objective: Most podiatry-led high-risk foot services (HRFS) in Australia are located in metropolitan areas or large regional centres. In rural areas, where there are limited specialist services, individuals with diabetes-related foot ulceration are more likely to undergo amputation. This study aimed to explore clinicians' perceptions of a recently implemented HRFS in rural New South Wales, Australia, and compare trends of amputation and hospitalisation prior to and post-implementation of the service.

Effect of Evobrutinib on Slowly Expanding Lesion Volume in Relapsing Multiple Sclerosis: A Post Hoc Analysis of a Phase 2 Trial.

Background And Objectives: Chronic active lesions (CALs) are demyelinated multiple sclerosis (MS) lesions with ongoing microglia/macrophage activity, resulting in irreversible neuronal damage and axonal loss. Evobrutinib is a highly selective, covalent, CNS-penetrant, Bruton tyrosine kinase inhibitor. This post hoc analysis evaluated the effect of evobrutinib on slowly expanding lesion (SEL) volume, an MRI marker of CALs, assessed baseline-week 48 in a phase 2, double-blind, randomized trial (NCT02975349) in relapsing MS (RMS).

Exotic Dark Matter Search with the Majorana Demonstrator.

With excellent energy resolution and ultralow-level radiogenic backgrounds, the high-purity germanium detectors in the Majorana Demonstrator enable searches for several classes of exotic dark matter (DM) models. In this work, we report new experimental limits on keV-scale sterile neutrino DM via the transition magnetic moment from conversion to active neutrinos ν_{s}→ν_{a}. We report new limits on fermionic dark matter absorption (χ+A→ν+A) and sub-GeV DM-nucleus 3→2 scattering (χ+χ+A→ϕ+A), and new exclusion limits for bosonic dark matter (axionlike particles and dark photons).

Avoiding ecosystem and social impacts of hydropower, wind, and solar in Southern Africa's low-carbon electricity system.

The scale at which low-carbon electricity will need to be deployed to meet economic growth, electrification, and climate goals in Africa is unprecedented, yet the potential land use and freshwater impacts from this massive build-out of energy infrastructure is poorly understood. In this study, we characterize low-impact onshore wind, solar photovoltaics, and hydropower potential in Southern Africa and identify the cost-optimal mix of electricity generation technologies under different sets of socio-environmental land use and freshwater constraints and carbon targets. We find substantial wind and solar potential after applying land use protections, but about 40% of planned or proposed hydropower projects face socio-environmental conflicts.

Geological evidence of extensive N-fixation by volcanic lightning during very large explosive eruptions.

Most of the nitrogen (N) accessible for life is trapped in dinitrogen (N), the most stable atmospheric molecule. In order to be metabolized by living organisms, N has to be converted into biologically assimilable forms, so-called fixed N. Nowadays, nearly all the N-fixation is achieved through biological and anthropogenic processes.