Identification of a novel nuclease activity in human DDX49 helicase.

Human DDX49 is an emerging target in cancer progression and retroviral diseases through its essential roles in nucleolar RNA processing. Here, we identify nuclease activity of human DDX49, which requires active site aspartate residues within a conserved region of metazoan DDX49s that is absent from yeast and archaeal DDX49 homologues. We provide evidence that DDX49 nuclease activity is facilitated by its helicase activity.

Pharmacokinetics of Tarlatamab, a Delta-Like Ligand-3 (DLL3) Targeted Half-Life Extended Bispecific T-Cell Engager (BiTE) Immunotherapy in Adult Patients with Previously Treated Small-Cell Lung Cancer: Results from DeLLphi-300, a Phase I Multiple-Dose-Escalation Study.

Background: Tarlatamab binds to delta-like ligand 3 on cancer cells and cluster of differentiation-3 on T cells, leading to T-cell-mediated tumor lysis, and has demonstrated a promising safety and efficacy profile in patients with previously treated small-cell lung cancer (SCLC). Here, we present pharmacokinetic results from DeLLphi-300 (NCT03319940), an ongoing international, open-label, first-in-human study in previously treated adult patients with SCLC.

Methods: Multiple escalating doses of tarlatamab were administered every 2 weeks (Q2W; 0.

Evaluating experimental, knowledge-based and computational cocrystal screening methods to advance drug-drug cocrystal fixed-dose combination development.

Fixed-dose combinations (FDCs) offer significant advantages to patients and the pharmaceutical industry alike through improved dissolution profiles, synergistic effects and extended patent lifetimes. Identifying whether two active pharmaceutical ingredients have the potential to form a drug-drug cocrystal (DDC) or interact is an essential step in determining the most suitable type of FDC to formulate. The lack of coherent strategies to determine if two active pharmaceutical ingredients that can be co-administered can form a cocrystal, has significantly impacted DDC commercialisation.

transformants expressing oxacillinases and metallo-β-lactamases that confer resistance to meropenem: new tools for anti- drug development and AMR preparedness.

Antimicrobial resistance (AMR) in is an unmet medical need. Multiple drug-resistant/extremely drug-resistant strains of do not display growth well in models, and consequently, their response to antibacterial therapy is inconsistent. We addressed this issue by engineering carbapenem resistance motifs into the highly virulent genetic background of AB5075.

Anaphylaxis to Patent Blue V Dye With Clinical Deterioration Following Administration of Suxamethonium and Sensitisation on Skin Testing to Methylene Blue, Patent Blue V Dye and Suxamethonium.

Neuromuscular blocking drugs (NMBAs) and Patent Blue V dye sodium salt 2.5% (Guerbet, Roissy, France) are frequently implicated in perioperative allergic immunoglobulin E (IgE) mediated anaphylaxis. Most cases of anaphylaxis during surgery occur at induction of anaesthesia, although reactions to vital dyes injected into soft tissues often show a delayed onset.

Classification of osteoarthritic and healthy cartilage using deep learning with Raman spectra.

Raman spectroscopy is a rapid method for analysing the molecular composition of biological material. However, noise contamination in the spectral data necessitates careful pre-processing prior to analysis. Here we propose an end-to-end Convolutional Neural Network to automatically learn an optimal combination of pre-processing strategies, for the classification of Raman spectra of superficial and deep layers of cartilage harvested from 45 Osteoarthritis and 19 Osteoporosis (Healthy controls) patients.

Ergonomic interventions to reduce upper limb musculoskeletal pain during robotic surgery: a narrative review.

There is a high prevalence of upper limb musculoskeletal pain among robotic surgeons. Poor upper limb ergonomic positioning during robotic surgery occurs when the shoulders are abducted, and the elbows are lifted off the console armrest. The validated rapid upper limb assessment can quantify ergonomic efficacy.

Evaluation of the Healthy Start voucher scheme on maternal vitamin use and child breastfeeding: a natural experiment using data linkage.

Background: Having a good start in life during pregnancy and infancy has been shown to be important for living both a healthy life and a longer life. Despite the introduction of many policies for the early-years age group, including voucher schemes, with the aim of improving nutrition, there is limited evidence of their impact on health.

Objectives: To assess the effectiveness of the Healthy Start voucher scheme on infant, child and maternal outcomes, and to capture the lived experiences of the Healthy Start voucher scheme for low-income women.

A Midwest Stakeholder Evaluation of an Adolescent and Young Adult Cancer Survivor Needs Assessment Survey.

Over 87,000 adolescents and young adults (AYAs) are diagnosed with cancer in the United States each year. Improvement in outcomes in the AYA population has lagged that of both younger and older patients. This decrement may be attributable to several factors, including insufficient supportive care services.

Archaeal Hel308 suppresses recombination through a catalytic switch that controls DNA annealing.

Hel308 helicases promote genome stability in archaea and are conserved in metazoans, where they are known as HELQ. Their helicase mechanism is well characterised, but it is unclear how they specifically contribute to genome stability in archaea. We show here that a highly conserved motif of Hel308/HELQ helicases (motif IVa, F/YHHAGL) modulates both DNA unwinding and a newly identified strand annealing function of archaeal Hel308.

Multi-objective topology optimisation for acoustic porous materials using gradient-based, gradient-free, and hybrid strategies.

When designing passive sound-attenuation structures, one of the challenging problems that arise is optimally distributing acoustic porous materials within a design region so as to maximise sound absorption while minimising material usage. To identify efficient optimisation strategies for this multi-objective problem, several gradient, non-gradient, and hybrid topology optimisation strategies are compared. For gradient approaches, the solid-isotropic-material-with-penalisation method and a gradient-based constructive heuristic are considered.

Spatial characterization and quantification of CD40 expression across cancer types.

Background: CD40, a TNF receptor family member, is expressed by a variety of immune cells and is involved in the activation of both adaptive and innate immune responses. Here, we used quantitative immunofluorescence (QIF) to evaluate CD40 expression on the tumor epithelium of solid tumors in large patient cohorts of lung, ovarian, and pancreatic cancers.

Methods: Tissue samples from nine different solid tumors (bladder, breast, colon, gastric, head and neck, non-small cell lung cancer (NSCLC), ovarian, pancreatic and renal cell carcinoma), constructed in tissue microarray format, were initially assessed for CD40 expression by QIF.

Benefit of Interdisciplinary Care in Resource Identification in an Adolescent and Young Adult Oncology Care Model.

There are limited data to identify the best care model to support the vulnerable adolescent and young adult (AYA) oncology population. We sought to compare the impact of AYA physician visits versus interdisciplinary team (IDT) care on AYA-specific resource identification and utilization, as well as to provide a model of AYA oncology care implementation. We identified AYA-aged patients 15-39 years with a current or prior history of cancer seen by the University of Wisconsin Carbone Cancer Center (UWCCC) AYA Oncology Program between January 21, 2021 and May 27, 2021.

The Impact of TSC-1 and -2 Mutations on Response to Therapy in Malignant PEComa: A Multicenter Retrospective Analysis.

Background: Perivascular epithelioid cell neoplasms (PEComas) are a diverse family of mesenchymal tumors with myomelanocytic differentiation that disproportionately affect women and can be associated with tuberous sclerosis (TS). Although mTOR inhibition is widely used as first-line treatment, it is unclear what genomic alterations exist in these tumors and how they influence the response to therapy.

Methods: This was a multicenter study conducted at five sites within the US.

NCCN Guidelines® Insights: Gastrointestinal Stromal Tumors, Version 2.2022.

Gastrointestinal stromal tumors (GIST) are the most common type of soft tissue sarcoma that occur throughout the gastrointestinal tract. Most of these tumors are caused by oncogenic activating mutations in the KIT or PDGFRA genes. The NCCN Guidelines for GIST provide recommendations for the diagnosis, evaluation, treatment, and follow-up of patients with these tumors.

Does past offending behaviors catch up with you? A study examining the relationship between traffic offending history and fatal crash involvement.

Objective: The aim of the current study was to compare the traffic histories of drivers fatally injured in a road traffic crash, to alive drivers of the same age and gender in order to determine if key markers of increased fatality-risk could be identified.

Methods: The case sample comprised 1,139 (82% male) deceased drivers, while the control sample consisted of 1,139 registered Queensland drivers (who were individually matched to the case sample on age and gender).

Results: Using a logistic regression model, and adjusting for age and gender, it was found that a greater number of offenses predicted greater odds of fatal crash involvement, with each increase in offense frequency category increasing ones' odds by 1.

Soft Tissue Sarcoma, Version 2.2022, NCCN Clinical Practice Guidelines in Oncology.

Soft tissue sarcomas (STS) are rare malignancies of mesenchymal cell origin that display a heterogenous mix of clinical and pathologic characteristics. STS can develop from fat, muscle, nerves, blood vessels, and other connective tissues. The evaluation and treatment of patients with STS requires a multidisciplinary team with demonstrated expertise in the management of these tumors.

Incidence and outcome of anaphylaxis in cardiac surgical patients.

Introduction: Anaphylaxis is a rare but serious and potentially fatal complication of anesthesia. Little is known about the incidence and outcome of anaphylaxis in cardiac surgical patients, which we aimed to investigate.

Methods: This was a 21-year retrospective study of cardiac surgical patients at Manchester Royal Infirmary, Manchester Foundation Trust, Manchester, UK.

Disparities in Treatment Satisfaction and Supportive Care Receipt for Young Adult Oncology Patients on the Basis of Residential Location.

Purpose: Adolescent and young adult oncology programs are critical but exist primarily in academic centers, prompting potential disparities in care on the basis of patient residence. We studied the impact of residential location on supportive care receipt and treatment satisfaction in young adults (YAs) with cancer age 19-39 years treated at the University of Wisconsin Carbone Cancer Center (UWCCC).

Methods: YA patients with cancer age 19-39 years seen at UWCCC from March 30, 2019, to March 29, 2020, were sent a survey assessing supportive care receipt and satisfaction.

Standardizing Research Training: a Pilot Curriculum Within a Hematology/Oncology Fellowship Program.

While scholarly activity is recognized as critical in cancer education, there is an outstanding need for methods to define research learning competencies and tools for formal research productivity and competency assessment. We piloted and studied a novel educational initiative within the University of Wisconsin Hematology/Oncology fellowship program, establishing a professional learning community (PLC) of research mentors and developing a formative evaluation tool, a research portfolio. We developed a PLC engaged in reflective conversations about intended learning outcomes and effective instructional strategies.

Versatile, but not focused, traffic offenders are more likely to be at fault for a fatal crash.

Introduction: The aim of this study was to determine whether drivers who had received more traffic infringements were more likely to be at fault for the crash in which they were killed.

Method: The current dataset was derived from the crash and traffic history records provided by the Queensland Department of Transport and Main Roads and Coroner's Court for every driver, with available records, who was killed in a crash in Queensland, Australia, between 2011 and 2019 (N = 1,136). The most common traffic offenses in the current sample were speeding, disobeying road rules, driving under the influence of drugs and alcohol, and unlicensed driving.

Pregnancy outcomes related to the treatment of sarcomas with anthracyclines and/or ifosfamide during pregnancy.

Background: Sarcomas are rare diagnoses but are seen with relative frequency in adolescents and young adults and thus can present in pregnancy. We sought to study the administration of anthracyclines and/or ifosfamide in pregnancy-associated sarcomas.

Patients And Methods: We conducted a multi-institutional retrospective study, identifying sarcoma patients who received anthracyclines and/or ifosfamide during pregnancy.