Stronger El Niños reduce tropical forest arthropod diversity and function.

There is ongoing debate about the vulnerability of arthropods to climate change. Long-term impacts of climate change on arthropod communities could manifest through short-term weather patterns. Arthropods in the tropics are hyper-diverse and contribute many crucial ecosystem functions, but are comparatively less studied than in temperate regions.

Novel Therapeutic Strategies for Metastatic Prostate Cancer Care.

Background And Objective: The elucidation of prostate cancer biology and genomics has led to new therapies improving disease outcomes with novel androgen receptor (AR) pathway inhibitors (ARPIs), taxanes, and targeted therapeutics that require disease molecular stratification.

Methods: We are presenting a narrative and qualitative synthesis based on a systematic search. Medline (PubMed) and Embase (OvidSP) were searched (October 1, 2024, covering 2019-2024) using keywords and Medical Subject Headings terms; ClinicalTrials.

Treatment-related adverse events of antibody drug-conjugates in clinical trials.

Background: Antibody-drug conjugates (ADCs) aim to enhance the therapeutic index of cytotoxic agents but can cause unexpected toxicities. This study evaluated adverse events (AEs) from phase 1 trials at The Royal Marsden Drug Development Unit (DDU) over a decade and pivotal phase 2 and 3 trials leading to FDA registration, correlating AEs with ADC components such as target, antibody, linker, payload, and Drug-to-Antibody Ratio (DAR).

Methods: We performed a retrospective cohort analysis of patients treated with ADCs in phase 1 trials (January 2014 to January 2024) compared to published phase 2-3 trials of FDA-approved ADCs.

Defactinib with avutometinib in patients with solid tumors: the phase 1 FRAME trial.

Use of signal transduction inhibitors as single agents to treat cancer leads to resistance because of the plasticity of intracellular signaling, and combination therapy can overcome this. We describe the first-in-human trial of avutometinib (RAF-MEK clamp) and defactinib (focal adhesion kinase inhibitor) in patients with solid tumors. The trial met its primary endpoint and recommended a phase 2 dose and schedule.

PERSEUS1: An Open-label, Investigator-initiated, Single arm, Phase 2 Trial Testing the Efficacy of Pembrolizumab in Patients with Metastatic Castration-resistant Prostate Cancer with Mismatch Repair Deficiency and Other Immune-sensitive Molecular Subtypes.

Background And Objective: Some metastatic castration-resistant prostate cancers (mCRPCs) present mismatch repair deficiency (MMRd) and other molecular subtypes potentially sensitive to immune checkpoint inhibitors (ICIs). The PERSEUS1 trial evaluated the response to pembrolizumab in these subtypes.

Methods: This open-label, investigator-initiated, single-arm, phase 2 trial used a two-stage Simon minimax design.

BH3 mimetics targeting BCL-XL have efficacy in solid tumors with RB1 loss and replication stress.

BH3 mimetic drugs that inhibit BCL-2, BCL-XL, or MCL-1 have limited activity in solid tumors. Through assessment of xenograft-derived 3D prostate cancer models and cell lines we find that tumors with RB1 loss are sensitive to BCL-XL inhibition. In parallel, drug screening demonstrates that disruption of nucleotide pools by agents including thymidylate synthase inhibitors sensitizes to BCL-XL inhibition, together indicating that replication stress increases dependence on BCL-XL.

Cost-effectiveness of early noninvasive cardiac testing for suspected acute coronary syndrome.

Background: Early noninvasive cardiac testing (NIT) is often performed in the initial workup of patients who present to the emergency department (ED) with suspected acute coronary syndrome (ACS). Our study objective was to calculate the cost-effectiveness of adopting early NIT for risk stratification to avoid future nonfatal acute myocardial infarction (MI) or death.

Methods: To obtain the incremental difference in cost and clinical outcomes, we first conducted a multicenter retrospective cohort study within the member population of the Kaiser Permanente Southern California integrated health care delivery system.

Association of Early Noninvasive Cardiac Stress Testing With Acute Myocardial Infarction and Mortality.

Study Objective: The evaluation for suspected acute coronary syndrome is a common and high-risk presentation in emergency departments (EDs). After exclusion of acute myocardial infarction (MI), patients often undergo early (within 72 hours) noninvasive cardiac testing. We evaluated the association between early noninvasive testing and death/acute MI in ED patients suspected of acute coronary syndrome.

NXP800 Activates the Unfolded Protein Response, Altering AR and E2F Function to Impact Castration-Resistant Prostate Cancer Growth.

Purpose: Advanced prostate cancer is invariably fatal, with the androgen receptor (AR) being a major therapeutic target. AR signaling inhibitors have improved overall survival for men with advanced prostate cancer, but treatment resistance is inevitable and includes reactivation of AR signaling. Novel therapeutic approaches targeting these mechanisms to block tumor growth is an urgent unmet clinical need.

On the identity of Opopaea euphorbicola Strand, 1909 and first records of three other non-native goblin spiders from Ascension Island (Araneae: Oonopidae).

N/A.

Impact of California's naloxone co-prescription law on emergency department visits, 30-day mortality, and prescription patterns.

Objective: Opioid overdose is a public health epidemic adversely impacting individuals and communities. To combat this, California passed a law mandating that prescribers offer a naloxone prescription in certain circumstances. Our objective was to evaluate associations with California's naloxone prescription mandate and emergency department (ED) overdose visits/hospitalizations, opioid and naloxone prescribing, and 30-day mortality.

SRSF6 modulates histone-chaperone HIRA splicing to orchestrate AR and E2F activity in prostate cancer.

Despite novel therapeutic strategies, advanced-stage prostate cancer (PCa) remains highly lethal, pointing out the urgent need for effective therapeutic strategies. While dysregulation of the splicing process is considered a cancer hallmark, the role of certain splicing factors remains unknown in PCa. This study focuses on characterizing the levels and role of SRSF6 in this disease.

AR coactivators, CBP/p300, are critical mediators of DNA repair in prostate cancer.

Castration resistant prostate cancer (CRPC) remains an incurable disease stage with ineffective treatments options. Here, the androgen receptor (AR) coactivators CBP/p300, which are histone acetyltransferases, were identified as critical mediators of DNA damage repair (DDR) to potentially enhance therapeutic targeting of CRPC. Key findings demonstrate that CBP/p300 expression increases with disease progression and selects for poor prognosis in metastatic disease.

Emerging frontiers in androgen receptor research for prostate Cancer: insights from the 2nd international androgen receptor Symposium.

Continued exploration of the androgen receptor (AR) is crucial, as it plays pivotal roles in diverse diseases such as prostate cancer (PCa), serving as a significant therapeutic focus. Therefore, the Department of Urology Dresden hosted an international meeting for scientists and clinical oncologists to discuss the newest advances in AR research. The 2nd International Androgen Receptor Symposium was held in Dresden, Saxony, Germany, from 26-27.

RNASEH2B loss and PARP inhibition in advanced prostate cancer.

BACKGROUNDClinical trials have suggested antitumor activity from PARP inhibition beyond homologous recombination deficiency (HRD). RNASEH2B loss is unrelated to HRD and preclinically sensitizes to PARP inhibition. The current study reports on RNASEH2B protein loss in advanced prostate cancer and its association with RB1 protein loss, clinical outcome, and clonal dynamics during treatment with PARP inhibition in a prospective clinical trial.

AR coactivators, CBP/p300, are critical mediators of DNA repair in prostate cancer.

Castration resistant prostate cancer (CRPC) remains an incurable disease stage with ineffective treatments options. Here, the androgen receptor (AR) coactivators CBP/p300, which are histone acetyltransferases, were identified as critical mediators of DNA damage repair (DDR) to potentially enhance therapeutic targeting of CRPC. Key findings demonstrate that CBP/p300 expression increases with disease progression and selects for poor prognosis in metastatic disease.

Inter- and Intra-Patient Repeatability of Radiomic Features from Multiparametric Whole-Body MRI in Patients with Metastatic Prostate Cancer.

(1) Background: We assessed the test-re-test repeatability of radiomics in metastatic castration-resistant prostate cancer (mCPRC) bone disease on whole-body diffusion-weighted (DWI) and T1-weighted Dixon MRI. (2) Methods: In 10 mCRPC patients, 1.5 T MRI, including DWI and T1-weighted gradient-echo Dixon sequences, was performed twice on the same day.

Computable phenotype for diagnostic error: developing the data schema for application of symptom-disease pair analysis of diagnostic error (SPADE).

Objectives: Diagnostic errors are the leading cause of preventable harm in clinical practice. Implementable tools to quantify and target this problem are needed. To address this gap, we aimed to generalize the Symptom-Disease Pair Analysis of Diagnostic Error (SPADE) framework by developing its computable phenotype and then demonstrated how that schema could be applied in multiple clinical contexts.

An all-inclusive model for predicting invasive bacterial infection in febrile infants age 7-60 days.

Background: Invasive bacterial infections (IBIs) in febrile infants are rare but potentially devastating. We aimed to derive and validate a predictive model for IBI among febrile infants age 7-60 days.

Methods: Data were abstracted retrospectively from electronic records of 37 emergency departments (EDs) for infants with a measured temperature >=100.

Thio-2 Inhibits Key Signaling Pathways Required for the Development and Progression of Castration-resistant Prostate Cancer.

Therapies that abrogate persistent androgen receptor (AR) signaling in castration-resistant prostate cancer (CRPC) remain an unmet clinical need. The N-terminal domain of the AR that drives transcriptional activity in CRPC remains a challenging therapeutic target. Herein we demonstrate that BCL-2-associated athanogene-1 (BAG-1) mRNA is highly expressed and associates with signaling pathways, including AR signaling, that are implicated in the development and progression of CRPC.