Retrieval Augmented Therapy Suggestion for Molecular Tumor Boards: Algorithmic Development and Validation Study.

Background: Molecular tumor boards (MTBs) require intensive manual investigation to generate optimal treatment recommendations for patients. Large language models (LLMs) can catalyze MTB recommendations, decrease human error, improve accessibility to care, and enhance the efficiency of precision oncology.

Objective: In this study, we aimed to investigate the efficacy of LLM-generated treatments for MTB patients.

Improving quality control procedures for the measurement of total daily energy expenditure using the two-point doubly labeled water method.

Rationale: The precision of the doubly labeled water (DLW) method is determined by the precision and accuracy of the isotopic measurements. Quality control (QC) procedures to mitigate sample variability require additional measurements if sample duplicates differ more than a factor of instrument precision. We explored the effect of widening QC ranges on total daily energy expenditure (TDEE) determined using the two-point sampling method.

Integration of 3D bioprinting and multi-algorithm machine learning identified glioma susceptibilities and microenvironment characteristics.

Glioma, with its heterogeneous microenvironments and genetic subtypes, presents substantial challenges for treatment prediction and development. We integrated 3D bioprinting and multi-algorithm machine learning as a novel approach to enhance the assessment and understanding of glioma treatment responses and microenvironment characteristics. The bioprinted patient-derived glioma tissues successfully recapitulated molecular properties and drug responses of native tumors.

US oil and gas system emissions from nearly one million aerial site measurements.

As airborne methane surveys of oil and gas systems continue to discover large emissions that are missing from official estimates, the true scope of methane emissions from energy production has yet to be quantified. We integrate approximately one million aerial site measurements into regional emissions inventories for six regions in the USA, comprising 52% of onshore oil and 29% of gas production over 15 aerial campaigns. We construct complete emissions distributions for each, employing empirically grounded simulations to estimate small emissions.

Brain Functional Connectivity and Anatomical Features as Predictors of Cognitive Behavioral Therapy Outcome for Anxiety in Youths.

Background: Because pediatric anxiety disorders precede the onset of many other problems, successful prediction of response to the first-line treatment, cognitive-behavioral therapy (CBT), could have major impact. However, existing clinical models are weakly predictive. The current study evaluates whether structural and resting-state functional magnetic resonance imaging can predict post-CBT anxiety symptoms.

Normalization of Fronto-Parietal Activation by Cognitive-Behavioral Therapy in Unmedicated Pediatric Patients With Anxiety Disorders.

Objective: Anxiety disorders are prevalent among youths and are often highly impairing. Cognitive-behavioral therapy (CBT) is an effective first-line treatment. The authors investigated the brain mechanisms associated with symptom change following CBT.

Evaluating the development and well-being assessment (DAWBA) in pediatric anxiety and depression.

Enhancing screening practices and developing scalable diagnostic tools are imperative in response to the increasing prevalence of youth mental health challenges. Structured lay psychiatric interviews have emerged as one such promising tool. However, there remains limited research evaluating structured psychiatric interviews, specifically their characterization of internalizing disorders in treatment-seeking youth.

The effects of inflammation and acidosis on placental blood vessels reactivity.

Introduction: Inflammation and acidosis are two stress stimuli that correspond to pathophysiological processes occurring in placental-mediated vascular disorders. We aimed to investigate the effects of these stimuli on placental chorionic blood vessels reactivity using the ex-vivo placental perfusion model.

Methods: Term placentas were obtained immediately after cesarean deliveries, and selected cotyledons were cannulated and dually perfused ex-vivo.

Akinetopsia: A Systematic Review.

Selective motion blindness, also known as akinetopsia, is infrequently reported in the literature. Hence, little is known about the condition including its causes, time course, pathophysiology, and current diagnostic methods. In this investigation, we comprehensively surveyed the literature using a systematic review to identify each reported case of the condition.

Placental disposition of cannabidiol: An ex vivo perfusion study.

Objective: In the absence of safety data in humans, the use of cannabidiol (CBD) is not recommended during pregnancy. Yet >50% of pregnancies in women with epilepsy are unintended, making fetal exposure to CBD possible. As a small-molecule, highly lipid-soluble drug, CBD is likely to be distributed into the placenta and cross it.

Prospective analysis to determine barriers to allogeneic hematopoietic cell transplantation in patients with acute leukemia.

Allogeneic hematopoietic cell transplantation (allo-HCT) is a potentially curative treatment for patients with acute leukemia. Despite this, studies have shown that only a minority of patients ultimately proceed to allo-HCT. The primary objective of this prospective, observational study was to identify the rate of allo-HCT in patients for whom it was recommended, and reasons why patients deemed appropriate and eligible for HCT did not subsequently undergo transplant.

Patient-Specific Pharmacokinetics and Dasatinib Nephrotoxicity.

Background: Dasatinib has been associated with nephrotoxicity. We sought to examine the incidence of proteinuria on dasatinib and determine potential risk factors that may increase dasatinib-associated glomerular injury.

Methods: We examined glomerular injury through urine albumin-creatinine ratio (UACR) in 82 patients with chronic myelogenous leukemia who were on tyrosine-kinase inhibitor therapy for at least 90 days.

Interaction between myelodysplasia-related gene mutations and ontogeny in acute myeloid leukemia.

Accurate classification and risk stratification are critical for clinical decision making in patients with acute myeloid leukemia (AML). In the newly proposed World Health Organization and International Consensus classifications of hematolymphoid neoplasms, the presence of myelodysplasia-related (MR) gene mutations is included as 1 of the diagnostic criteria for AML, AML-MR, based largely on the assumption that these mutations are specific for AML with an antecedent myelodysplastic syndrome. ICC also prioritizes MR gene mutations over ontogeny (as defined in the clinical history).

Family Planning and Pregnancy in Patients with Chronic Myeloid Leukemia.

Purpose Of Review: The goal of this review is to summarize what is known about pregnancy in women with chronic myeloid leukemia (CML): there are very few guidelines regarding how to treat women who are pregnant at the time of CML diagnosis, and similarly, few guidelines regarding family planning for women already on tyrosine kinase inhibitor therapy who might want to start family planning.

Recent Findings: Most patients with CML achieve excellent control with first line tyrosine kinase inhibitor therapy that includes either imatinib, dasatinib, nilotinib, or bosutinib. For men, tyrosine kinase inhibitor (TKI) therapy does not affect sperm number or function, and female partners of men on therapy who become pregnant do not have an increased risk of miscarriage or babies with fetal malformation.

Lacosamide effects on placental carriers of essential compounds in comparison with valproate: Studies in perfused human placentas.

Objective: Lacosamide is increasingly being prescribed to pregnant women, although its effects on the developing fetus have not been fully clarified yet. Previously, we have shown that several antiseizure medications, particularly valproate, can affect the expression of carriers of essential compounds in placental cells. Here, our aim was to assess the effect of short ex vivo exposure of human placentas to lacosamide on the expression of carriers of essential nutrients required by the human fetus.

Is the Critical Care Resuscitation Unit Sustainable: A 5-Year Experience of a Beneficial and Novel Model.

Background: The 6-bed critical care resuscitation unit (CCRU) is a unique and specialized intensive care unit (ICU) that streamlines the interhospital transfer (IHT-transfer between different hospitals) process for a wide range of patients with critical illness or time-sensitive disease. Previous studies showed the unit successfully increased the number of ICU admissions while reducing the time of transfer in the first year of its establishment. However, its sustainability is unknown.

Quantifying Regional Methane Emissions in the New Mexico Permian Basin with a Comprehensive Aerial Survey.

Limiting emissions of climate-warming methane from oil and gas (O&G) is a major opportunity for short-term climate benefits. We deploy a basin-wide airborne survey of O&G extraction and transportation activities in the New Mexico Permian Basin, spanning 35 923 km, 26 292 active wells, and over 15 000 km of natural gas pipelines using an independently validated hyperspectral methane point source detection and quantification system. The airborne survey repeatedly visited over 90% of the active wells in the survey region throughout October 2018 to January 2020, totaling approximately 98 000 well site visits.

Retrospective analysis of arterial occlusive events in the PACE trial by an independent adjudication committee.

Background: The phase 2 PACE (Ponatinib Ph+ ALL and CML Evaluation) trial of ponatinib showed robust long-term benefit in relapsed Philadelphia chromosome-positive (Ph+) leukemia; arterial occlusive events (AOEs) occurred in ≥ 25% of patients based on investigator reporting. However, AOE rates vary depending on the definitions and reporting approach used.

Methods: To better understand clinically relevant AOEs with ponatinib, an independent cardiovascular adjudication committee reviewed 5-year AOE data from the PACE trial according to a charter-defined process and standardized event definitions.

Not your usual drug-drug interactions: Monoclonal antibody-based therapeutics may interact with antiseizure medications.

Therapeutic monoclonal antibodies (mAbs) have emerged as the fastest growing drug class. As such, mAbs are increasingly being co-prescribed with other drugs, including antiseizure medications (ASMs). Although mAbs do not share direct targets or mechanisms of disposition with small-molecule drugs (SMDs), combining therapeutics of both types can increase the risk of adverse effects and treatment failure.