Larotrectinib Treatment for Patients With TRK Fusion-Positive Salivary Gland Cancers.

Background: Larotrectinib is a first-in-class, highly selective, and central nervous system-active tropomyosin receptor kinase (TRK) inhibitor approved for the treatment of adult and pediatric patients with TRK fusion cancer. We report the efficacy and safety of larotrectinib in patients with TRK fusion-positive salivary gland cancers.

Patients And Methods: Patients with TRK fusion-positive salivary gland cancer treated with larotrectinib were identified from two clinical trials (NCT02122913 and NCT02576431).

Variation in Survival and Gut Microbiome Composition of Hatchery-Grown Native Oysters at Various Locations within the Puget Sound.

The Olympia oyster () of the Puget Sound suffered a dramatic population crash, but restoration efforts hope to revive this native species. One overlooked variable in the process of assessing ecosystem health is association of bacteria with marine organisms and the environments they occupy. Oyster microbiomes are known to differ significantly between species, tissue type, and the habitat in which they are found.

Cavitating Lung Disease Associated With Sudden Death.

A 16-year-old boy presented with 6 days of left iliac fossa pain. He had a medical history of right subtalar dislocation and appendicitis requiring laparotomy 3 years earlier, complicated by wound dehiscence. His family history was significant for his brother's sudden death 3 weeks prior after a 12-month illness with intermittent epigastric pain, weight loss, and hemoptysis.

An Exploratory Study of a New Vancomycin Eye Drops Formulation for Extemporaneous Compounding.

Purpose: Compounded eye drop solutions of vancomycin hydrochloride have important clinical applications, such as postoperative antimicrobial prophylaxis and bacterial keratitis. There exists a plethora of data to support the use of various liquid vehicles to compound vancomycin hydrochloride eye drops. However, there are a number of limitations for implementation, especially the frequent shortage or discontinuation of the vehicle products.

Effects of 'Healthy' Fecal Microbiota Transplantation against the Deterioration of Depression in Fawn-Hooded Rats.

Depression is a recurrent, heterogeneous mood disorder occurring in more than 260 million people worldwide. Gut microbiome dysbiosis is associated with the development of depressive-like behaviors by modulating neuro-biochemical metabolism through the microbiome-gut-brain (MGB) axis. Fecal microbiota transplantation (FMT) has been proposed as a potential therapeutic solution for depression, but the therapeutic efficiency and mechanism are unknown.

Effect of encapsulated protein on the dynamics of lipid sponge phase: a neutron spin echo and molecular dynamics simulation study.

Lipid membranes are highly mobile systems with hierarchical, time and length scale dependent, collective motions including thickness fluctuations, undulations, and topological membrane changes, which play an important role in membrane interactions. In this work we have characterised the effect of encapsulating two industrially important enzymes, β-galactosidase and aspartic protease, in lipid sponge phase nanoparticles on the dynamics of the lipid membrane using neutron spin echo (NSE) spectroscopy and molecular dynamics (MD) simulations. From NSE, reduced membrane dynamics were observed upon enzyme encapsulation, which were dependent on the enzyme concentration and type.

Cyclooxygenase-Inhibiting Platinum(IV) Prodrugs with Potent Anticancer Activity.

Platinum(IV) prodrugs of the [Pt(P)(A)(COXi)(OH)] type scaffold (where P is 1,10-phenanthroline or 5,6-dimethyl-1,10-phenanthroline, A is 1,2-diaminocyclohexane, and COXi is a COX inhibitor, either indomethacin or aspirin) were synthesised and characterised, and their biological activity was explored. MTT assays showed that these complexes exhibit outstanding activity against a range of cancer cell lines, and nanomolar activities were observed. The most potent complex, , exhibited a GI of 3 nM in the Du145 prostate cancer cell line and was observed to display a 1614-fold increased activity against the HT29 colon cancer cell line relative to cisplatin.

Safety and Efficacy of Avelumab in Small Bowel Adenocarcinoma.

Introduction: Small bowel adenocarcinomas (SBAs) are rare and frequently treated like large intestinal adenocarcinomas. However, SBAs have a very different microenvironment and could respond differently to the same therapies. Our previous data suggested that SBAs might benefit from targeting the PD-1/PD-L1 axis based on PD-L1 staining in almost 50% of SBA tissue samples tested.

Multi-qubit entanglement and algorithms on a neutral-atom quantum computer.

Gate-model quantum computers promise to solve currently intractable computational problems if they can be operated at scale with long coherence times and high-fidelity logic. Neutral-atom hyperfine qubits provide inherent scalability owing to their identical characteristics, long coherence times and ability to be trapped in dense, multidimensional arrays. Combined with the strong entangling interactions provided by Rydberg states, all the necessary characteristics for quantum computation are available.

The impact of maternal asthma on the preterm infants' gut metabolome and microbiome (MAP study).

Preterm infants are at a greater risk for the development of asthma and atopic disease, which can lead to lifelong negative health consequences. This may be due, in part, to alterations that occur in the gut microbiome and metabolome during their stay in the Neonatal Intensive Care Unit (NICU). To explore the differential roles of family history (i.

Phylogeny-Aware Analysis of Metagenome Community Ecology Based on Matched Reference Genomes while Bypassing Taxonomy.

We introduce the operational genomic unit (OGU) method, a metagenome analysis strategy that directly exploits sequence alignment hits to individual reference genomes as the minimum unit for assessing the diversity of microbial communities and their relevance to environmental factors. This approach is independent of taxonomic classification, granting the possibility of maximal resolution of community composition, and organizes features into an accurate hierarchy using a phylogenomic tree. The outputs are suitable for contemporary analytical protocols for community ecology, differential abundance, and supervised learning while supporting phylogenetic methods, such as UniFrac and phylofactorization, that are seldom applied to shotgun metagenomics despite being prevalent in 16S rRNA gene amplicon studies.

A Predictive Coding Framework for Understanding Major Depression.

Predictive coding models of brain processing propose that top-down cortical signals promote efficient neural signaling by carrying predictions about incoming sensory information. These "priors" serve to constrain bottom-up signal propagation where prediction errors are carried via feedforward mechanisms. Depression, traditionally viewed as a disorder characterized by negative cognitive biases, is associated with disrupted reward prediction error encoding and signaling.

Long-term fretting corrosion performance of modular head-neck junctions with self-reinforced composite gaskets from PEEK and UHMWPE.

Soft gasket-like polymer films may provide multiple advantages in inhibiting fretting corrosion between metal-hard surfaces in total joint implants. Self-reinforced composites (SRC's) made from either poly(ether ether ketone), SRC-PEEK, or ultra high molecular weight polyethylene, SRC-PE, were fabricated and tested to investigate their ability to limit or prevent mechanically assisted corrosion in modular taper devices. Hot compaction was used to create nominally 100 μm thick unidirectional composite gaskets.

The development of interprofessional education and collaborative practice in Latin America and the Caribbean: preliminary observations.

The Pan-American Health Organization (PAHO) and World Health Organization have encouraged countries across Latin America and the Caribbean (LAC) to incorporate interprofessional education and collaborative practice (IPECP) into policies on the health workforce, and support policymakers in expanding its use. PAHO recommend countries to promote the development of interprofessional teams in integrated health services networks using IPECP. The creation of the Regional Network for Interprofessional Education in the Americas, the mobilization of a series of IPECP regional meetings, and the development of national IPECP action plans are the most promising results achieved thus far.

Postradioiodine Graves' management: The PRAGMA study.

Objective: Thyroid status in the months following radioiodine (RI) treatment for Graves' disease can be unstable. Our objective was to quantify frequency of abnormal thyroid function post-RI and compare effectiveness of common management strategies.

Design: Retrospective, multicentre and observational study.

Benefits of GLP-1 (Glucagon-Like Peptide 1) Receptor Agonists for Stroke Reduction in Type 2 Diabetes: A Call to Action for Neurologists.

People living with diabetes are at higher risk for stroke and have a poorer prognosis following a stroke event than those without diabetes. Data from cardiovascular outcome trials and meta-analyses indicate that GLP-1RAs (glucagon-like peptide 1 receptor agonists) reduce the risk of stroke in individuals with type 2 diabetes. Accordingly, many guidelines now recommend the addition of GLP-1RAs to ongoing antihyperglycemic regimens to lower the risk of stroke in type 2 diabetes.

Activate Your Health: impact of a real-life programme promoting healthy lifestyle habits in Canadian workers.

The workplace has been suggested as a good setting for the promotion of healthy lifestyles. This article examines the impact of Activate Your Health programme, provided over an average of 1.35 years, on employee health and lifestyle habits (actual and intention to improve).

Intrathecal Delivery of Therapeutic Oligonucleotides for Potent Modulation of Gene Expression in the Central Nervous System.

Therapeutic oligonucleotides hold tremendous potential for treating central nervous system (CNS) disorders. The route of administration of oligonucleotides significantly impacts both distribution and silencing efficiency. Here, we describe a technically simple, clinically relevant method to administer oligonucleotide compounds into the CNS via direct intrathecal injections.

Improvement Predictors in a Workplace Program Promoting Healthy Lifestyle Habits.

Background: The baseline characteristics of employees to predict improvements in healthy lifestyle habits (LHs) following workplace health promotion programs are underexplored. This study sought to identify predictors of improvements in physical activity (PA), eating habits, sleep habits, and stress management, and health risk factors resulting from healthy LHs.

Methods: The Activate Your Health program included 3 packages of an increasing number of interventions: light, moderate, and high.

Conceptual strategies for characterizing interactions in microbial communities.

Understanding the sets of inter- and intraspecies interactions in microbial communities is a fundamental goal of microbial ecology. However, the study and quantification of microbial interactions pose several challenges owing to their complexity, dynamic nature, and the sheer number of unique interactions within a typical community. To overcome such challenges, microbial ecologists must rely on various approaches to distill the system of study to a functional and conceptualizable level, allowing for a practical understanding of microbial interactions in both simplified and complex systems.

Gestational Insulin Resistance Is Mediated by the Gut Microbiome-Indoleamine 2,3-Dioxygenase Axis.

Background & Aims: Normal gestation involves a reprogramming of the maternal gut microbiome (GM) that contributes to maternal metabolic changes by unclear mechanisms. This study aimed to understand the mechanistic underpinnings of the GM-maternal metabolism interaction.

Methods: The GM and plasma metabolome of CD1, NIH-Swiss, and C57 mice were analyzed with the use of 16S rRNA sequencing and untargeted liquid chromatography-mass spectrometry throughout gestation.

Machine learning for emerging infectious disease field responses.

Emerging infectious diseases (EIDs), including the latest COVID-19 pandemic, have emerged and raised global public health crises in recent decades. Without existing protective immunity, an EID may spread rapidly and cause mass casualties in a very short time. Therefore, it is imperative to identify cases with risk of disease progression for the optimized allocation of medical resources in case medical facilities are overwhelmed with a flood of patients.