Humanized Candida and NanoBiT Assays Expedite Discovery of Bdf1 Bromodomain Inhibitors With Antifungal Potential.

The fungal Bromodomain and Extra-Terminal (BET) protein Bdf1 is a potential antifungal target against invasive fungal infections. However, the need to selectively inhibit both Bdf1 bromodomains (BDs) over human orthologs and the lack of molecular tools to assess on-target antifungal efficacy hamper efforts to develop Bdf1 BD inhibitors as antifungal therapeutics. This study reports a phenyltriazine compound that inhibits both Bdf1 BDs from the human fungal pathogen Candida glabrata with selectivity over the orthologous BDs from the human BET protein Brd4.

Psychological mechanisms underlying the biased interpretation of numerical scientific evidence.

Do people use their statistical expertise selectively to reach preferred conclusions when evaluating scientific evidence, with those more expert showing more preferential bias? We investigated this motivated numeracy account of evidence evaluation but came to a different account for biased evaluation. Across three studies ( = 2,799), participants interpreted numerical data from gun control intervention studies. In Studies 1 and 2, participants reached accurate conclusions more frequently from scientific data when those data aligned with their political preferences than when they did not, an attitude congeniality effect.

Association Between the Sequence of β-lactam and Vancomycin Administration and Mortality in Patients with Suspected Sepsis.

Background: Timely antibiotic initiation is critical to sepsis management, but there are limited data on the impact of giving β-lactams first vs vancomycin first amongst patients prescribed both agents.

Methods: We retrospectively analyzed all adults admitted to 5 US hospitals from 2015-2022 with suspected sepsis (blood culture collected, antibiotics administered, and organ dysfunction) treated with vancomycin and a broad-spectrum β-lactam within 24h of arrival. We estimated associations between β-lactam vs vancomycin first strategies and in-hospital mortality using inverse probability weighting (IPW) to adjust for potential confounders.

Loss of DOT1L function disrupts neuronal transcription, animal behavior, and leads to a novel neurodevelopmental disorder.

Individuals with monoallelic pathogenic variants in the histone lysine methyltransferase DOT1L display global developmental delay and varying congenital anomalies. However, the impact of monoallelic loss of remains unclear. Here, we present a largely female cohort of 11 individuals with variants with developmental delays and dysmorphic facial features.

Multistate outbreak of Oranienburg infections linked to bulb onions imported from Mexico - United States, 2021.

In 2021, the U.S. Food and Drug Administration (FDA), the Centers for Disease Control and Prevention (CDC), and state and local health and regulatory partners investigated an outbreak of serovar Oranienburg infections linked to bulb onions from Mexico, resulting in 1040 illnesses and 260 hospitalizations across 39 states, the District of Columbia, and Puerto Rico.

Gene model for the ortholog of in .

Gene model for the ortholog of Phosphatase and tensin homolog ( ) in the Apr. 2013 (UC Berkeley DroMir_2.2/DmirGB2) Genome Assembly (GenBank Accession: GCA_000269505.

Assessment of Racial, Ethnic, and Sex-Based Disparities in Time-to-Antibiotics and Sepsis Outcomes in a Large Multihospital Cohort.

Objectives: To characterize associations between race/ethnicity/sex, time-to-antibiotics, and mortality in patients with suspected sepsis or septic shock.

Design: Retrospective cohort study, with race/ethnicity/sex as the exposure, and time-to-antibiotics (relative to emergency department arrival) and in-hospital mortality as the outcome.

Setting: Five Massachusetts hospitals.

Surgery and postoperative definitive radiotherapy for management of canine soft tissue sarcoma: a multi-institutional retrospective study of 272 dogs (2010-2020).

Objective: To report local progression and survival in dogs following surgery and postoperative definitive radiotherapy (dRT) for management of soft tissue sarcoma (STS) and to evaluate risk factors for local progression and survival.

Methods: Records were retrospectively reviewed at 9 referral hospitals for dogs managed with postoperative dRT between January 1, 2010, and January 1, 2020, following surgery for STS. Data related to presentation, surgery, dRT, systemic therapy, and outcome were abstracted.

Validation of a semi-quantitative scoring system and workflow for analysis of fluorescence quantification in companion animals.

Significance: Many commercially available near-infrared (NIR) fluorescence imaging systems lack algorithms for real-time quantifiable fluorescence data. Creation of a workflow for clinical assessment and analysis may provide clinical researchers with a method for intraoperative fluorescence quantification to improve objective outcome measures.

Aim: Scoring systems and verified image analysis are employed to determine the amount and intensity of fluorescence within surgical specimens both intra and postoperatively.

Best practices for recruitment in veterinary clinical trials.

A successful clinical trial requires participants, but many factors can impede effective study recruitment. To better recruit for quality veterinary clinical trials in client-owned animals that lead to improved evidence-based patient care and outcomes, there is a collective need to share and implement current best practices for recruitment strategies. These strategies should utilize a holistic view of recruitment, encompassing study design and logistics, representative participation, incentives, personnel resources, advertising, and participant retention.

Morbidity and Mortality of Hospital-Onset SARS-CoV-2 Infections Due to Omicron Versus Prior Variants : A Propensity-Matched Analysis.

Background: Many hospitals have scaled back measures to prevent nosocomial SARS-CoV-2 infection given large decreases in the morbidity and mortality of SARS-CoV-2 infections for most people. Little is known, however, about the morbidity and mortality of nosocomial SARS-CoV-2 infections for hospitalized patients in the Omicron era.

Objective: To estimate the effect of nosocomial SARS-CoV-2 infection on hospitalized patients' outcomes during the pre-Omicron and Omicron periods.

Prospective assessment of canine thyroid cancer-part I: nodal metastatic rate and impact of nodal immunohistochemistry in 70 dogs.

Objective: To determine the rate of nodal metastasis in dogs with thyroid cancer and evaluate whether immunohistochemistry (IHC) identifies additional metastases beyond evaluation with H&E.

Animals: 70 prospectively enrolled client-owned dogs with thyroid cancer managed with thyroidectomy.

Methods: Dogs underwent thyroidectomy with concurrent elective bilateral medial retropharyngeal (MRP) ± deep cervical lymphadenectomy.

Intramuscular diacylglycerol accumulates with acute hyperinsulinemia in insulin-resistant phenotypes.

Elevated skeletal muscle diacylglycerols (DAGs) and ceramides can impair insulin signaling, and acylcarnitines (acylCNs) reflect impaired mitochondrial fatty acid oxidation, thus, the intramuscular lipid profile is indicative of insulin resistance. Acute (i.e.

Canine preclinical safety evaluation of a multimodal nanoparticle agent (Nanotrast-CF800) for image-guided cancer surgery.

Surgical oncology often requires the use of contrast-enhanced cross-sectional imaging preoperatively to characterize solitary tumours and identify sentinel lymph nodes. Intraoperative optical guidance can effectively aid tissue-sparing tumour excision and locate sentinel lymph nodes. Nanotrast-CF800 (CF800) is a novel dual-modality contrast agent, which co-encapsulates iohexol and indocyanine green (ICG) within a liposomal nanoparticle.

Modifying the Basicity of the dNTP Leaving Group Modulates Precatalytic Conformational Changes of DNA Polymerase β.

The catalytic function of DNA polymerase β (pol β) fulfills the gap-filling requirement of the base excision DNA repair pathway by incorporating a single nucleotide into a gapped DNA substrate resulting from the removal of damaged DNA bases. Most importantly, pol β can select the correct nucleotide from a pool of similarly structured nucleotides to incorporate into DNA in order to prevent the accumulation of mutations in the genome. Pol β is likely to employ various mechanisms for substrate selection.

Comparative aspects of targeted sentinel lymph node mapping in veterinary and human medicine: opportunities for future research.

There is a significant overlap in the genetic, metabolic and epigenetic alterations between human and companion animal cancers, including those of the oral cavity, breast, bladder, skin, lungs and pancreas. In many cancer types, the identification and removal of affected lymph nodes are essential for accurate cancer management, including treatment and prognosis. Historically, lymphadenectomy and subsequent radical resection based on regional anatomy, palpation and lymph node aspirates were considered sufficient; however, modern approaches with sentinel lymph node mapping (SLN) mapping have increased the accuracy of surgical decision-making.