Heart Failure Part 3: Diuretic Management in Older People.

Heart failure is a common condition in the older population. As severity progresses, fluid accumulates resulting in congestive symptoms. Loop diuretics are the cornerstone of managing fluid overload and dosing should target euvolemia and congestive symptoms.

Use of Essential Medicines for Pain Relief and Palliative Care: A Global Consensus Process.

Context: The WHO Model List of Essential Medicines includes 24 medications under the section Medicines for Pain and Palliative Care (EML). The Lancet Commission on Pain and Palliative Care developed the Lancet Essential Package (LEP), including 35 medications designed to alleviate serious health-related suffering worldwide.

Objectives: This study aims to provide recommendations on the appropriate use of essential of medicines in palliative care.

Mobocertinib antagonizes multidrug resistance in ABCB1- and ABCG2-overexpressing cancer cells: In vitro and in vivo studies.

Overexpression of ATP-binding cassette (ABC) transporters, particularly ABCB1 and ABCG2, strongly correlates with multidrug resistance (MDR), rendering cancer chemotherapy ineffective. Exploration and identification of novel inhibitors targeting ABCB1 and ABCG2 are necessary to overcome the related MDR. Mobocertinib is an approved EGFR/HER2 inhibitor for non-small cell lung cancer (NSCLC) with EGFR exon 20 insertion mutations.

The workshops on computational applications in secondary metabolite discovery (CAiSMD).

We report the outcomes of the second session of the free online open-access workshop "Computational Applications in Secondary Metabolite Discovery (CAiSMD) 2022" that took place from 09 to 11 March 2022. The first session was held from 08 to 10 March 2021 and drew the attention of many early career scientists from academia and industry. The 23 invited speakers of this year's workshop also came from academia and industry and 222 registered participants from five continents (Africa, Asia, Europe, South, and North America) took part in the workshop.

Randomized Trial of Self-Guided, Internet-Based, Cognitive Behavior Therapies for Migraine.

Background: Self-guided Internet-based cognitive behavior therapy (iCBT) for migraine interventions could improve access to care, but there is poor evidence of their efficacy.

Methods: A three-arm randomized controlled trial compared: iCBT focused on psychoeducation, self-monitoring and skills training (SPHERE), iCBT focused on identifying and managing personal headache triggers (PRISM) and a waitlist control. The primary treatment outcome was a ≥ 50% reduction in monthly headache days at 4 months post-randomization.

Repurposing of c-MET Inhibitor Tivantinib Inhibits Pediatric Neuroblastoma Cellular Growth.

Dysregulation of receptor tyrosine kinase c-MET is known to promote tumor development by stimulating oncogenic signaling pathways in different cancers, including pediatric neuroblastoma (NB). NB is an extracranial solid pediatric cancer that accounts for almost 15% of all pediatric cancer-related deaths, with less than a 50% long-term survival rate. In this study, we analyzed a large cohort of primary NB patient data and revealed that high expression strongly correlates with poor overall survival, disease progression, relapse, and high levels in NB patients.

Scrolling Your Sleep Away: The Effects of Bedtime Device Use on Sleep Among Young Adults with Poor Sleep.

Background: Many young adults report sleep problems, including insufficient sleep and poor sleep quality. Young adults are heavily reliant on electronic devices, even using them during bedtime with adverse effects on sleep. Given the importance of adequate sleep, the present study examined the daily association between using electronic devices during bedtime and sleep in a diverse sample of young adults with poor sleep.

State of the Science: The Hierarchical Taxonomy of Psychopathology (HiTOP).

The Hierarchical Taxonomy of Psychopathology (HiTOP) is a dimensional framework for psychopathology advanced by a consortium of nosologists. In the HiTOP system, psychopathology is grouped hierarchically from super-spectra, spectra, and subfactors at the upper levels to homogeneous symptom components and maladaptive traits and their constituent symptoms, and maladaptive behaviors at the lower levels. HiTOP has the potential to improve clinical outcomes by planning treatment based on symptom severity rather than heterogeneous diagnoses, targeting treatment across different levels of the hierarchy, and assessing distress and impairment separately from the observed symptom profile.

Predictive immunoinformatics reveal promising safety and anti-onchocerciasis protective immune response profiles to vaccine candidates (Ov-RAL-2 and Ov-103) in anticipation of phase I clinical trials.

Onchocerciasis (river blindness) is a debilitating tropical disease that causes significant eye and skin damage, afflicting millions worldwide. As global efforts shift from disease management to elimination, vaccines have become crucial supplementary tools. The Onchocerciasis Vaccine for Africa (TOVA) Initiative was established in 2015, to advance at least one vaccine candidate initially targeting onchocerciasis in infants and children below 5 years of age, through Phase I human trials by 2025.

Transformer-based active learning for multi-class text annotation and classification.

Objective: Data-driven methodologies in healthcare necessitate labeled data for effective decision-making. However, medical data, particularly in unstructured formats, such as clinical notes, often lack explicit labels, making manual annotation challenging and tedious.

Methods: This paper introduces a novel deep active learning framework designed to facilitate the annotation process for multiclass text classification, specifically using the SOAP (subjective, objective, assessment, plan) framework, a widely recognized medical protocol.

Necrotizing Pancreatitis Due to Very High Triglyceride Level: A Case Report.

In the United States, acute pancreatitis is one of the most common gastrointestinal conditions that results in hospital admission. Necrotizing pancreatitis is a form of acute pancreatitis that can lead to various local and systemic complications. It is also associated with a high risk of mortality and morbidity without prompt intervention.

The identification of essential cellular genes is critical for validating drug targets.

Accurately identifying biological targets is crucial for advancing treatment options. Essential genes, vital for cell or organism survival, hold promise as potential drug targets in disease treatment. Although many studies have sought to identify essential genes as therapeutic targets in medicine and bioinformatics, systematic reviews on their relationship with drug targets are relatively rare.

Cell-Based Screen Identifies a Highly Potent and Orally Available ABCB1 Modulator for Treatment of Multidrug Resistance.

Targeting ABCB1 is a promising strategy in combating multidrug resistance. Our cell-based phenotypic screening led to the discovery of novel triazolo[1,5-]pyrimidone-based ABCB1 modulators. Notably, was identified as a significant contributor to heightened sensitization of human colorectal adenocarcinoma cells (SW620/Ad300) to paclitaxel (IC = 5 nM).

Synthesis and evaluation of novel tetrahydroisoquinoline-benzo[h]chromen-4-one conjugates as dual ABCB1/CYP1B1 inhibitors for overcoming MDR in cancer.

The emergence of multidrug resistance (MDR) in malignant tumors is one of the major threats encountered currently by many chemotherapeutic agents. Among the various mechanisms involved in drug resistance, P-glycoprotein (P-gp, ABCB1), a member of the ABC transporter family that significantly increases the efflux of various anticancer drugs from tumor cells, and the metabolic enzyme CYP1B1 are widely considered to be two critical targets for overcoming MDR. Unfortunately, no MDR modulator has been approved by the FDA to date.

The Role of the Extracellular Matrix in the Pathogenesis and Treatment of Pulmonary Emphysema.

Pulmonary emphysema involves progressive destruction of alveolar walls, leading to enlarged air spaces and impaired gas exchange. While the precise mechanisms responsible for these changes remain unclear, there is growing evidence that the extracellular matrix plays a critical role in the process. An essential feature of pulmonary emphysema is damage to the elastic fiber network surrounding the airspaces, which stores the energy needed to expel air from the lungs.

Nrf2/Keap1/ARE regulation by plant secondary metabolites: a new horizon in brain tumor management.

Brain cancer is regarded as one of the most life-threatening forms of cancer worldwide. Oxidative stress acts to derange normal brain homeostasis, thus is involved in carcinogenesis in brain. The Nrf2/Keap1/ARE pathway is an important signaling cascade responsible for the maintenance of redox homeostasis, and regulation of anti-inflammatory and anticancer activities by multiple downstream pathways.

The correlation between cancer stem cells and epithelial-mesenchymal transition: molecular mechanisms and significance in cancer theragnosis.

The connections between cancer stem cells (CSCs) and epithelial-mesenchymal transition (EMT) is critical in cancer initiation, progression, metastasis, and therapy resistance, making it a focal point in cancer theragnosis. This review provides a panorama of associations and regulation pathways between CSCs and EMT, highlighting their significance in cancer. The molecular mechanisms underlined EMT are thoroughly explored, including the involvement of key transcription factors and signaling pathways.

The interplay between popularity and aggression in adolescence: Focusing the lens on sense of power and prestige.

There is accumulating longitudinal evidence that popularity predicts relative increases in adolescents' aggression. Yet, we know very little about the conditions that motivate popular youth to engage in coercive behaviors. In this study, we evaluated whether popular adolescents would show elevated levels of aggression over time when they felt powerless and had low prestige (respect and admiration) among their peers.