Return of Clinically Actionable Pharmacogenetic Results From Molecular Tumor Board DNA Sequencing Data: Workflow and Estimated Costs.

Pharmacogenetic testing can prevent severe toxicities from several oncology drug therapies; it also has the potential to improve the outcomes from supportive care drugs. Paired tumor and germline sequencing is increasingly common in oncology practice; these include sequencing of pharmacogenes, but the germline pharmacogenetic variants are rarely included in the clinical reports, despite many being clinically actionable. We established an informatics workflow to evaluate the clinical sequencing results for pharmacogenetic variants.

Deception and Fraud in the Justification of "Pediatric Drug Development": A Challenge at the Interface of Medicine and Law.

United States and European Union laws demand separate clinical studies in children as a condition for drugs' marketing approval. Justified by carefully framed pseudo-scientific wordings, more so the European Medicines Agency than the United States Food and Drug Administration, "Pediatric Drug Development" is probably the largest abuse in medical research in history. Preterm newborns are immature and vulnerable, but they grow.

Mesenchymal stromal cells promote the formation of lung cancer organoids via Kindlin-2.

Background: Patient-derived lung cancer organoids (PD-LCOs) demonstrate exceptional potential in preclinical testing and serve as a promising model for the multimodal management of lung cancer. However, certain lung cancer cells derived from patients exhibit limited capacity to generate organoids due to inter-tumor or intra-tumor variability. To overcome this limitation, we have created an in vitro system that employs mesenchymal stromal cells (MSCs) or fibroblasts to serve as a supportive scaffold for lung cancer cells that do not form organoids.

Secreted LGALS3BP facilitates distant metastasis of breast cancer.

Background: Patients with estrogen receptor (ER)-positive breast cancer (BC) can be treated with endocrine therapy targeting ER, however, metastatic recurrence occurs in 25% of the patients who have initially been treated. Secreted proteins from tumors play important roles in cancer metastasis but previous methods for isolating secretory proteins had limitations in identifying novel targets.

Methods: We applied an in situ secretory protein labeling technique using TurboID to analyze secretome from tamoxifen-resistant (TAMR) BC.

Plasma S100β is a predictor for pathology and cognitive decline in Alzheimer's disease.

Background: Blood-brain barrier dysfunction is one characteristic of Alzheimer's disease (AD) and is recognized as both a cause and consequence of the pathological cascade leading to cognitive decline. The goal of this study was to assess markers for barrier dysfunction in postmortem tissue samples from research participants who were either cognitively normal individuals (CNI) or diagnosed with AD at the time of autopsy and determine to what extent these markers are associated with AD neuropathologic changes (ADNC) and cognitive impairment.

Methods: We used postmortem brain tissue and plasma samples from 19 participants: 9 CNI and 10 AD dementia patients who had come to autopsy from the University of Kentucky AD Research Center (UK-ADRC) community-based cohort; all cases with dementia had confirmed severe ADNC.

Histamine N-methyltransferase (HNMT) as a potential auxiliary biomarker for predicting adaptability to anti-HER2 drug treatment in breast cancer patients.

Background: Up to 23% of breast cancer patients recurred within a decade after trastuzumab treatment. Conversely, one trial found that patients with low HER2 expression and metastatic breast cancer had a positive response to trastuzumab-deruxtecan (T-Dxd). This indicates that relying solely on HER2 as a single diagnostic marker to predict the efficacy of anti-HER2 drugs is insufficient.

Concerns Regarding the Use of Kirchhoff's Laws in Pharmacokinetics.

Over the last two years the idea that the principles presented in Kirchhoff's circuit and voltage laws also pertain to pharmacokinetics (1-3). It is claimed that these principles make the elimination in the liver and kidney more straight forward to model and provide a rationale for understanding why sometimes during bioavailability studies one arrives at bioavailability values greater than 100%. In this paper it will be shown that these claims are based on incorrect translations of the Kirchhoff's Laws to pharmacokinetics.

Magnetic nano-sized solid acid catalyst bearing sulfonic acid groups for biodiesel synthesis and oxidation of sulfides.

In this study, the AlFeO@n-Pr@Et-SOH heterogeneous catalyst was successfully synthesized and utilized to produce biodiesel from oleic acid through an esterification process and to oxidize sulfides. To examine the physicochemical characteristics of the AlFeO@n-Pr@Et-SOH nanomaterial, a variety of advanced techniques were employed, including Fourier Transform infrared spectroscopy (FT-IR), Field emission scanning electron microscopy (FE-SEM), Energy dispersive X-ray spectroscopy (EDX), Vibrating sample magnetometer (VSM), Elemental Mapping, Transmission electron microscopy (TEM), Inductively coupled plasma (ICP), and X-ray diffraction (XRD). The AlFeO@n-Pr@Et-SOH materials demonstrated excellent performance in both the esterification of oleic acid and the oxidation of sulfides.

Pyrene functionalized organic cation receptor-based "turn-on" fluorescence approach for monitoring of chlorpyrifos in food, soil, and water samples.

Background: The unregulated use of pesticides by farmers, for crop productivity results in widespread contamination of organophosphates in real environmental samples, which is a growing societal concern about their potential health effects. The conventional approaches for the monitoring these organophosphate-based pesticides which include immunoassays, electrochemical methods, immunosensors, various chromatography techniques, along with some spectroscopic methods, are either costly, sophisticated, or involves the use of different metal complexes. Therefore, there is an urgent need for sensitive, quick, and easy-to-use detection techniques for the screening of widely used organophosphate-based pesticides.

Serially coupled columns enhance rapid separation and predictive interaction understanding of 93 fentanyl analogs.

Background: The simplicity of synthesis methods has facilitated the illegal manufacture of various fentanyl analogs, leading to numerous fatal overdoses worldwide, particularly in North America. Fentanyl analogs with similar structures are difficult to distinguish due to their fragmentation patterns, making separation using chromatography essential. Additionally, because fentanyl analogs are lethal even in trace amounts, they are easily smuggled, and commonly used fentanyl test strips often fail to detect them due to their low sensitivity.

Effectiveness of shared decision making strategies for stroke prevention among patients with atrial fibrillation: cluster randomized controlled trial.

Objective: To evaluate the effectiveness of multiple decision aid strategies in promoting high quality shared decision making for prevention of stroke in patients with non-valvular atrial fibrillation.

Design: Cluster randomized controlled trial.

Setting: Six academic medical centers in the United States.

Bibliometric analysis: A few suggestions (Part Two).

This manuscript serves as a follow-up to our previous work, "Bibliometric Analysis: A Few Suggestions," where we highlighted key aspects of bibliometric research and offered recommendations for improving its rigor. In this draft, we expand on those ideas and provide additional suggestions aimed at enhancing the depth and scope of bibliometric analysis. By analyzing 36 randomly selected bibliometric studies, we identified common practices and gaps in the field, which informed the inclusion of new recommendations not covered in our earlier paper.

Review of porous microspheres for enzyme immobilization: Strategies, applications, and prospects.

Enzymes are natural biocatalysts with the advantages such as high catalytic efficiency, and strong substrate selectivity. However, the features of structure instability and low reusability rates have limited the industrial applications of enzyme. Fortunately, advancements in technology have made enzyme immobilization possible.

Event-driven PrEP beyond cisgender men who have sex with men.

Despite advancements in existing antiretroviral-based prevention strategies, including daily oral, locally acting, and injectable options, there is a pressing need for more inclusive and flexible event-driven pre-exposure prophylaxis (PrEP) strategies for all. Event-driven or intermittent dosing of PrEP in populations beyond cisgender men who have sex with men would offer a promising alternative by fitting prevention into the diverse lifestyles of affected populations and thereby advancing health equity. Evidence from PrEP clinical trials, pharmacokinetic studies, modelling studies, and real-world observational research suggests that event-driven PrEP could be a flexible and inclusive option, yet optimal dosing has not been established across sex and gender spectrums.

Targeting JNK3 for Alzheimer's disease: Design and synthesis of novel inhibitors with aryl group diversity utilizing wide pocket.

JNK3, a brain-specific stress-activated protein kinase, plays a critical role in Alzheimer's disease pathogenesis through phosphorylation of Tau and APP. This study aimed to develop selective JNK3 inhibitors based on a pyrazole scaffold, focusing on (E)-1-(2-aminopyrimidin-4-yl)-4-styryl-1H-pyrazole-3-carboxamide derivatives. Through systematic structural modifications and extensive SAR analysis, we identified compounds 24a and 26a as highly potent JNK3 inhibitors, with IC values of 12 and 19 nM, respectively.

Portable and real-time detection for tetracycline antibiotics using europium-doped LDH gel intercalated graphene quantum dots.

Tetracyclines (TCs) residues pose a significant threat to the aquatic environment and human health, therefore this study aims to develop a simple, rapid, and sensitive TCs detection method. Herein, a dual-responsive gel probe (LDH-CES@N) was designed, consisting of the intercalation of graphene quantum dots into europium-doped layered double hydroxide (LDH). In the presence of TCs, the as-prepared probe exhibited dual emission fluorescence at 504 nm and 616 nm due to the synergistic effect of aggregation-induced emission and antenna effect.

The MYB-bHLH-NRAMP module modulates the cadmium sensitivity of quinoa by regulating cadmium transport and absorption.

Cadmium (Cd) is one of the most dangerous environmental pollutants and is easily absorbed by food crops. Quinoa is a kind of coarse grain crop with rich nutrition and strong stress resistance, which is easy to accumulate Cd. The increasingly serious soil Cd pollution poses a serious threat to the food safety of quinoa.

Post-marketing safety of antiseizure medications: Focus on serious adverse effects including drug reaction with eosinophilia and systemic symptoms (DRESS).

Purpose: On November 28, 2023, the U.S. FDA issued a Drug Safety Communication, warning that antiseizure medications (ASMs) levetiracetam and clobazam can cause a rare but serious reaction, drug reaction with eosinophilia and systemic symptoms (DRESS).

ACNO hydrogel enhances diabetic wound healing by modulating the Bcl-2/Bax/Caspase-3/PARP pathway.

Centella asiatica (L.) Urban, one of the authentic medicinal materials from Guizhou Province in China, has been traditionally applied for the treatment of contusions and fractures, as well as for promoting wound healing. Preliminary research suggests that asiaticoside-nitric oxide hydrogel (ACNO) exhibits the potential to enhance the healing of diabetic wounds (DWs); however, the underlying molecular mechanisms require further elucidation.

Integrative physiological, biochemical, and proteomic analysis of the leaves of two cotton genotypes under heat stress.

Cotton (Gossypium hirsutum L.), a crucial global fibre and oil seed crop faces diverse biotic and abiotic stresses. Among these, temperature stress strongly influences its growth, prompting adaptive physiological, biochemical, and molecular changes.

An interprofessional model to improve LGBTQ+ specific cultural competence in dental and pharmacy students.

Background: Disproportionate access to healthcare services among the Lesbian, Gay, Bisexual, Transgender, Queer or Questioning and others (LGBTQ+) population can be partially attributed to the lack of cultural competence among healthcare providers. The aim of this study was to evaluate the impact of an interprofessional model in improving cultural competence and clinical preparedness among dental and pharmacy students for providing LGBTQ+ specific care.

Methodology: This study is a retrospective observational study which used a novel interprofessional model of three different LGBTQ+ focused educational interventions within a group of dental and pharmacy students.

Longer Total Interhospital Transfer Times for Rural Sepsis Patients Not Associated with Increased Mortality.

Objectives: Sepsis is a time-sensitive condition, and many rural emergency department (ED) sepsis patients are transferred to tertiary hospitals. The objective of this study was to determine whether longer transport times during interhospital transfer are associated with higher sepsis mortality or increased hospital length-of-stay (LOS).

Methods: A cohort of rural adult (age ≥ 18y) sepsis patients transferred between hospitals were identified in the TELEmedicine as a Virtual Intervention for Sepsis Care in Emergency Departments (TELEVISED) parent study.

Identification of Naloxone in Emergency Medical Services Data Substantially Improves by Processing Unstructured Patient Care Narratives.

Objectives: Structured data fields, including medication fields involving naloxone, are routinely used to identify opioid overdoses in emergency medical services (EMS) data; between January 2021 and March 2024, there were approximately 1.2 million instances of naloxone administration. in the United States.

Integrating machine learning and structural dynamics to explore B-cell lymphoma-2 inhibitors for chronic lymphocytic leukemia therapy.

Chronic lymphocytic leukemia (CLL) is a malignancy caused by the overexpression of the anti-apoptotic protein B-cell lymphoma-2 (BCL-2), making it a critical therapeutic target. This study integrates computational screening, molecular docking, and molecular dynamics to identify and validate novel BCL-2 inhibitors from the ChEMBL database. Starting with 836 BCL-2 inhibitors, we performed ADME and Lipinski's Rule of Five (RO5) filtering, clustering, maximum common substructure (MCS) analysis, and machine learning models (Random Forest, SVM, and ANN), yielding a refined set of 124 compounds.