Tracheal tuft cells release ATP and link innate to adaptive immunity in pneumonia.

Tracheal tuft cells shape immune responses in the airways. While some of these effects have been attributed to differential release of either acetylcholine, leukotriene C4 and/or interleukin-25 depending on the activating stimuli, tuft cell-dependent mechanisms underlying the recruitment and activation of immune cells are incompletely understood. Here we show that Pseudomonas aeruginosa infection activates mouse tuft cells, which release ATP via pannexin 1 channels.

Plasma cell-free DNA chromatin immunoprecipitation profiling depicts phenotypic and clinical heterogeneity in advanced prostate cancer.

Cell phenotype underlies prostate cancer presentation and treatment resistance and can be regulated by epigenomic features. However, the osteotropic tendency of prostate cancer limits access to metastatic tissue, meaning most prior insights into prostate cancer chromatin biology are from preclinical models that do not fully represent disease complexity. Noninvasive chromatin immunoprecipitation of histones in plasma cell-free in humans may enable capture of disparate prostate cancer phenotypes.

Randomized Phase II Study of Durvalumab with or without Tremelimumab in Patients with Metastatic Castration-Resistant Prostate Cancer.

Purpose: PD-L1 is overexpressed by dendritic cells in patients with metastatic castration-resistant prostate cancer (mCRPC) progressing on androgen receptor pathway inhibitors. We tested whether checkpoint blockade could enhance antitumor activity in mCRPC.

Patients And Methods: In a multicenter open-label noncomparative randomized phase II study, patients with mCRPC treated with ≤1 prior cytotoxic chemotherapy, with measurable disease and progression on abiraterone and/or enzalutamide, were randomized to durvalumab 1,500 mg intravenously every 4 weeks ±4 doses of tremelimumab 75 mg intravenously.

Ultrafast photochemical processes in 1,2-dichloroethene measured with a universal XUV probe.

The presence of two chlorine atoms in 1,2-dichloroethene allows for isomerization around the double bond. This isomerization can lead to rich photochemistry. We present a time-resolved pump-probe photoelectron spectroscopy measurement on both the - and - isomers of 1,2-dichloroethene.

Review of clinical trials and guidelines for children and youth with mucopolysaccharidosis: outcome selection and measurement.

Background: To inform the development of a core outcome set (COS) for children and youth with mucopolysaccharidoses (MPS), we aimed to identify all outcomes and associated outcome measurement instruments that are reported in recent clinical trials and recommended as measurements in clinical management guidelines.

Methods: To identify English-language clinical trials and guidelines pertaining to MPS published between 2011 and mid-2021, we applied a comprehensive peer-reviewed search strategy to relevant databases and registers on May 16, 2021. Two reviewers independently screened retrieved citations and then full-text articles to determine eligibility for inclusion.

Plasma ctDNA as a Treatment Response Biomarker in Metastatic Cancers: Evaluation by the RECIST Working Group.

Early indicators of metastatic cancer response to therapy are important for evaluating new drugs and stopping ineffective treatment. The RECIST guidelines based on repeat cancer imaging are widely adopted in clinical trials, are used to identify active regimens that may change practice, and contribute to regulatory approvals. However, these criteria do not provide insight before 6 to 12 weeks of treatment and typically require that patients have measurable disease.

A Targeted Methylation-Based Multicancer Early Detection Blood Test Preferentially Detects High-Grade Prostate Cancer While Minimizing Overdiagnosis of Indolent Disease.

Purpose: Indolent prostate cancer (PCa) is prevalent in the intended use population (adults age 50-79 years) for blood-based multicancer early detection (MCED) tests. We examined the detectability of PCa by a clinically validated, targeted methylation-based MCED test.

Methods: Detectability by Gleason grade group (GG), clinical stage, association of detection status with tumor methylated fraction (TMeF), and overall survival (OS) were assessed in substudy 3 of Circulating Cell-Free Genome Atlas (CCGA; ClinicalTrials.

Rapid morphological change in UK populations of Impatiens glandulifera.

The highly invasive Impatiens glandulifera (Himalayan balsam) is one of the most prolific and widespread invasive plants in the British Isles. Introduced in the early nineteenth century, it has now been reported in almost every vice county across the UK and is a fierce competitor that has adverse effects on the local community structure. Despite the negative impacts that invaders like I.

Ocean weather, biological rates, and unexplained global ecological patterns.

As on land, oceans exhibit high temporal and spatial temperature variation. This "ocean weather" contributes to the physiological and ecological processes that ultimately determine the patterns of species distribution and abundance, yet is often unrecognized, especially in tropical oceans. Here, we tested the paradigm of temperature stability in shallow waters (<12.

Precision symptom phenotyping identifies early clinical and proteomic predictors of distinct COVID-19 sequelae.

Background: Post-COVID conditions (PCC) are difficult to characterize, diagnose, predict, and treat due to overlapping symptoms and poorly understood pathology. Identifying inflammatory profiles may improve clinical prognostication and trial endpoints.

Methods: 1,988 SARS-CoV-2 positive U.

Capturing and managing genetic diversity in ex situ collections of threatened tropical trees: A case study in .

Premise: Although ex situ collections of threatened plants are most useful when they contain maximal genetic variation, the conservation and maintenance of genetic diversity in collections are often poorly known. We present a case study using population genomic analyses of an ex situ collection of , a critically endangered tropical tree from Tanzania. Only ~43 individuals are known in two wild populations, and ex situ collections containing 34 individuals were established in two sites from wild-collected seed.

Access to the full three-dimensional Brillouin zone with time resolution, using a new tool for pump-probe angle-resolved photoemission spectroscopy.

Here, we report the first time- and angle-resolved photoemission spectroscopy (TR-ARPES) with the new Fermiologics "FeSuMa" analyzer. The new experimental setup has been commissioned at the Artemis laboratory of the UK Central Laser Facility. We explain here some of the advantages of the FeSuMa for TR-ARPES and discuss how its capabilities relate to those of hemispherical analyzers and momentum microscopes.

A heterogeneous pharmaco-transcriptomic landscape induced by targeting a single oncogenic kinase.

Over-activation of the epidermal growth factor receptor (EGFR) is a hallmark of glioblastoma. However, EGFR-targeted therapies have led to minimal clinical response. While delivery of EGFR inhibitors (EGFRis) to the brain constitutes a major challenge, how additional drug-specific features alter efficacy remains poorly understood.

Toward Informed Selection and Interpretation of Clinical Genomic Tests in Prostate Cancer.

Clinical genomic testing of patient germline, tumor tissue, or plasma cell-free DNA can enable a personalized approach to cancer management and treatment. In prostate cancer (PCa), broad genotyping tests are now widely used to identify germline and/or somatic alterations in and other DNA damage repair genes. Alterations in these genes can confer cancer sensitivity to poly (ADP-ribose) polymerase inhibitors, are linked with poor prognosis, and can have potential hereditary cancer implications for family members.

Multiregion sampling of de novo metastatic prostate cancer reveals complex polyclonality and augments clinical genotyping.

De novo metastatic prostate cancer is highly aggressive, but the paucity of routinely collected tissue has hindered genomic stratification and precision oncology. Here, we leveraged a rare study of surgical intervention in 43 de novo metastatic prostate cancers to assess somatic genotypes across 607 synchronous primary and metastatic tissue regions plus circulating tumor DNA. Intra-prostate heterogeneity was pervasive and impacted clinically relevant genes, resulting in discordant genotypes between select primary restricted regions and synchronous metastases.

Music in medical education: A critical interpretive synthesis.

Introduction: While many have championed the value of music in medical education, research specific to how and why music has been offered in medical education is sparse and there have been few attempts to synthesise the literature.

Methods: A Critical Interpretive Synthesis (CIS) of 56 texts including published articles, correspondence, abstracts and one thesis published between 1977 and 2022 was undertaken to explore the evidence basis for offering music in medical education.

Results: A total of 52 music-focused programmes/activities were described, encompassing both curricular and extra-curricular, receptive and participatory music activities and a wide range of musical genres.

Phase 1b study of enzalutamide plus CC-115, a dual mTORC1/2 and DNA-PK inhibitor, in men with metastatic castration-resistant prostate cancer (mCRPC).

Background: CC-115, a dual mTORC1/2 and DNA-PK inhibitor, has promising antitumour activity when combined with androgen receptor (AR) inhibition in pre-clinical models.

Methods: Phase 1b multicentre trial evaluating enzalutamide with escalating doses of CC-115 in AR inhibitor-naive mCRPC patients (n = 41). Primary endpoints were safety and RP2D.