Trastuzumab Plus Pertuzumab Versus Cetuximab Plus Irinotecan in Patients With Wild-Type, HER2-Positive, Metastatic Colorectal Cancer (S1613): A Randomized Phase II Trial.

Purpose: overexpression/amplification in wild-type (WT) metastatic colorectal cancer (mCRC; human epidermal growth factor receptor 2 [HER2]-positive mCRC) appears to be associated with limited benefit from anti-EGFR antibodies and promising responses to dual-HER2 inhibition; however, comparative efficacy has not been investigated. We conducted a randomized phase II trial to evaluate efficacy and safety of dual-HER2 inhibition against standard-of-care anti-EGFR antibody-based therapy as second/third-line treatment in HER2-positive mCRC.

Methods: Patients with -WT mCRC after central confirmation of HER2 positivity (immunohistochemistry 3+ or 2+ and in situ hybridization amplified [HER2/CEP17 ratio >2.

Prostate Cancer Risk Prediction Model Using Clinical and Magnetic Resonance Imaging-Related Findings: Impact of Combining Lesions' Locations and Apparent Diffusion Coefficient Values.

Objectives: The aims of the study are to develop a prostate cancer risk prediction model that combines clinical and magnetic resonance imaging (MRI)-related findings and to assess the impact of adding Prostate Imaging-Reporting and Data System (PI-RADS) ≥3 lesions-level findings on its diagnostic performance.

Methods: This 3-center retrospective study included prostate MRI examinations performed with clinical suspicion of clinically significant prostate cancer (csPCa) between 2018 and 2022. Pathological diagnosis within 1 year after the MRI was used to diagnose csPCa.

Diabetes, Subclinical Myocardial Injury or Stress and Risk of Heart Failure Subtypes: The Jackson Heart Study.

Objective: To assess the extent to which the concomitant presence of subclinical myocardial injury or stress and diabetes affects the risk of heart failure (HF) subtypes.

Research Design And Methods: The Jackson Heart Study included Black adults, categorized based on diabetes status, high-sensitivity cardiac troponin I (hs-cTnI), and brain natriuretic peptide (BNP) levels. Subclinical myocardial injury was defined as hs-cTnI ≥4 ng/L in women and ≥6 ng/L in men, and subclinical myocardial stress as BNP ≥35 pg/mL.

Completion of lunar magma ocean solidification at 4.43 Ga.

Crystallization of the lunar magma ocean yielded a chemically unique liquid residuum named KREEP. This component is expressed as a large patch on the near side of the Moon and a possible smaller patch in the northwest portion of the Moon's South Pole-Aitken basin on the far side. Thermal models estimate that the crystallization of the lunar magma ocean (LMO) could have spanned from 10 and 200 My, while studies of radioactive decay systems have yielded inconsistent ages for the completion of LMO crystallization covering over 160 My.

Sampling Mars: Geologic context and preliminary characterization of samples collected by the NASA Mars 2020 Perseverance Rover Mission.

The NASA Mars 2020 Perseverance Rover Mission has collected samples of rock, regolith, and atmosphere within the Noachian-aged Jezero Crater, once the site of a delta-lake system with a high potential for habitability and biosignature preservation. Between sols 109 and 1,088 of the mission, 27 sample tubes have been sealed, including witness tubes. Each sealed sample tube has been collected along with detailed documentation provided by the Perseverance instrument payload, preserving geological and environmental context.

The value of returning a sample of the Martian atmosphere.

The elemental and isotopic abundances of major species in the Martian atmosphere have been determined, but analyses often lack sufficient precision, and those of minor and trace species are frequently not well known. Many important questions about the evolution and current state of Mars require the kind of knowledge that can be gained from analysis of a returned sample of the Martian atmosphere. Key target species include the noble gases, nitrogen, and various species containing carbon, hydrogen, and oxygen, such as methane.

High organofluorine concentrations in municipal wastewater affect downstream drinking water supplies for millions of Americans.

Wastewater receives per- and polyfluoroalkyl substances (PFAS) from diverse consumer and industrial sources, and discharges are known to be a concern for drinking water quality. The PFAS family includes thousands of potential chemical structures containing organofluorine moieties. Exposures to a few well-studied PFAS, mainly perfluoroalkyl acids (PFAA), have been associated with increased risk of many adverse health outcomes, prompting federal drinking water regulations for six compounds in 2024.

Influenza vaccine effectiveness against medically attended outpatient illness, United States, 2023-24 season.

Background: The 2023-24 U.S. influenza season was characterized by a predominance of A(H1N1)pdm09 virus circulation with co-circulation of A(H3N2) and B/Victoria viruses.

Memory enhancement by transcranial radiofrequency wave treatment occurs without appreciably increasing brain temperature.

We have previously shown in small studies that full brain Transcranial Radiofrequency Wave Treatment (TRFT) to subjects with Alzheimer's Disease could stop and reverse their cognitive decline. An 8-emitter head device, the "MemorEM", was used in these studies to provide TRFT at 915 MHz frequency and power level of 1.6 W/kg Specific Absorption Rate (SAR) during daily 1-hour treatments.

Ethical Considerations in the Use of Artificial Intelligence in Pain Medicine.

Although the integration of artificial intelligence (AI) into medicine and healthcare holds transformative potential, significant challenges must be necessarily addressed. This technological innovation requires a commitment to ethical principles. Key issues concern autonomy, reliability, and bias.

Groundwater Ages in Intertill and Buried Valley Aquifers in Saskatchewan, Canada.

Continental glaciations during the Pleistocene Epoch created complex systems of aquifers and aquitards across many northern regions of the Earth. The low hydraulic conductivities of glacial till aquitards suggest that limited recharge will reach the underlying aquifers, potentially preserving old groundwaters. Here, we characterize the recharge history in intertill and buried valley aquifers in Saskatchewan, Canada using C, H, He δH, δO, and major ions.

Approaches for extracting daily dosage from free-text prescription signatures in heart failure with reduced ejection fraction: a comparative study.

Objective: To compare various methods for extracting daily dosage information from prescription signatures (sigs) and identify the best performers.

Materials And Methods: In this study, 5 daily dosage extraction methods were identified. Parsigs, RxSig, Sig2db, a large language model (LLM), and a bidirectional long short-term memory (BiLSTM) model were selected.

Addressing the unmet need in NSCLC progression with advances in second-line therapeutics.

Lung cancer is the leading cause of cancer mortality globally, with non-small cell lung cancer (NSCLC) accounting for 85% of cases. Despite advancements in first-line treatments such as immunotherapy and targeted therapies, resistance to these treatments is common, creating a significant unmet need for effective second-line therapies. This review evaluates current and emerging second-line therapeutic options for advanced or metastatic NSCLC, focusing on their efficacy and potential to improve patient outcomes.

The role of MEK inhibition in pediatric low-grade gliomas.

Pediatric low-grade gliomas (pLGGs) are the most common brain tumors in children. Many patients with unresectable tumors experience recurrence or long-term sequelae from standard chemotherapeutics. This mini-review explores the emerging role of MEK inhibitors in the management of pLGGs, highlighting their potential to transform current treatment paradigms.

Trends and Outcomes in Sarcomatoid Renal Cell Carcinoma: Analysis of the National Cancer Data Base.

Background And Objective: Our aim was to determine the clinical characteristics, temporal trends, and survival outcomes for sarcomatoid-dedifferentiated renal cell carcinoma (sRCC), as sRCC has historically had poor prognosis and a contemporary cohort has not been well characterized in a population-based study.

Methods: Data for 302 630 RCC cases from 2010 to 2019 were extracted from the National Cancer Data Base, of which 4.1% (12 329) were sRCC.

Changing Treatment and Metastatic Disease Patterns in Patients with EGFR Mutated NSCLC: An Academic Thoracic Medical Investigator's Consortium Registry Analysis.

Introduction: Osimertinib is now a standard first-line (1L) therapy for EGFR-mutated (EGFRm) advanced NSCLC. We aimed to characterize patterns of therapy and longitudinal risk of brain and liver metastasis in a cohort of EGFRm NSCLC.

Methods: Patients with metastatic EGFRm NSCLC who received 1L systemic therapy at sites within the Academic Thoracic Medical Investigator's Consortium were included; demographic and clinical data including treatment patterns were described.

Polygenic risk for epigenetic aging and adverse life experiences interact to predict growth in adolescent depression in a racially/ethnically diverse sample.

Introduction: Research has yet to examine the interplay between indices of environmental risk and resilience processes and genetic predisposition for epigenetic aging in predicting early adolescent depressive symptoms. In the current study we examine whether adverse life events and parental acceptance moderate polygenic predisposition for GrimAge epigenetic aging in predicting trajectories of depressive symptoms across early adolescence.

Method: Using data from the Adolescent Brain Development Study (ABCD, N = 11,875), we created polygenic scores for GrimAge, and examined whether exposure to adverse life events and parental acceptance moderated the relation between genetic risk and depressive symptom trajectories from age 10/11 to 12/13 using growth mixture modelling.

Wyburn-Mason disease: Management of a Spetzler-Martin grade 5 arteriovenous malformation with predominant thalamic involvement.

Wyburn-Mason disease (WMD) is a rare congenital phakomatosis known for its complex arteriovenous malformations (AVMs) predominantly affecting the brain and ocular structures. We present the case of a 19-year-old female with an unruptured Spetzler-Martin grade 5 left thalamic AVM, who initially exhibited progressive visual impairment and migraines. Following diagnosis, she was treated with trametinib, a MEK inhibitor; however, nine months later, she developed acute complications, including left monocular blindness and right hemisensory loss.