Super pan-genome reveals extensive genomic variations associated with phenotypic divergence in Actinidia.

Kiwifruit is an economically and nutritionally important horticultural fruit crop worldwide. The genomic data of several kiwifruit species have been released, providing an unprecedented opportunity for pan-genome analysis to comprehensively investigate the inter- and intra-species genetic diversity and facilitate utilization for kiwifruit breeding. Here, we generated a kiwifruit super pan-genome using 15 high-quality assemblies of eight Actinidia species.

Role of Hb to RDW ratio in metastatic renal cell carcinoma patients treated with first-line immunotherapy combinations.

Background: The present study aimed to investigate the prognostic and predictive roles of Hb/RDW ratio in patients with mRCC treated with first-line immunotherapy combinations (TKI plus ICI or ICI plus ICI).

Materials And Methods: We performed a sub-analysis of a multicenter retrospective observational study (ARON-1 project) involving patients with mRCC treated with first-line immunotherapy combinations.

Results: Three hundred and twenty-nine patients were enrolled, 244 males and 85 females.

Advancing Principled Pharmacoepidemiologic Research to Support Regulatory and Healthcare Decision Making: The Era of Real-World Evidence.

A compilation of factors over the past decade-including the availability of increasingly large and rich healthcare datasets, advanced technologies to extract unstructured information from health records and digital sources, advancement of principled study design and analytic methods to emulate clinical trials, and frameworks to support transparent study conduct-has ushered in a new era of real-world evidence (RWE). This review article describes the evolution of the RWE era, including pharmacoepidemiologic methods designed to support causal inferences regarding treatment effects, the role of regulators and other health authorities in establishing distributed real-world data networks enabling analytics at scale, and the many global guidance documents on principled methods of producing RWE. This article also highlights the growing opportunity for RWE to support decision making by regulators, health technology assessment groups, clinicians, patients, and other stakeholders and provides examples of influential RWE studies.

Double trouble: two retrotransposons triggered a cascade of invasions in Drosophila species within the last 50 years.

Horizontal transfer of genetic material in eukaryotes has rarely been documented over short evolutionary timescales. Here, we show that two retrotransposons, Shellder and Spoink, invaded the genomes of multiple species of the melanogaster subgroup within the last 50 years. Through horizontal transfer, Spoink spread in D.

Denosumab and clinical outcomes among men with osteoporosis: a retrospective cohort study.

Unlabelled: Most subjects in osteoporosis clinical trials were women with postmenopausal osteoporosis and while bridging studies (BMD endpoint) provide an expectation that osteoporosis medications will reduce fracture risk in men. This real-world study shows direct evidence of fracture risk reduction among men with osteoporosis (36% of hip fracture reduction with denosumab).

Purpose: Direct evidence for fracture risk reduction of medications used among men with osteoporosis is very limited.

Extreme hot weather events and risk of hospitalisation for cardiovascular and respiratory diseases in older people in Hong Kong in 2012 to 2018.

Background: The older population is more vulnerable to the impact of extreme hot weather events (EHWEs), while the impact on the frailer institutionalised older population was seldom assessed. Our objective was to assess the relationship between EHWEs and hospitalisation risks among institutionalised and community-dwelling older people.

Methods: We used territory-wide hospitalisation record of Hong Kong from year 2012 to 2018 to assess the associations between EHWEs and cardiovascular and respiratory disease hospitalisations in the population aged 65 or above.

Glucagon-Like Peptide 1 Receptor Agonists and Risk of Thyroid Cancer: An International Multisite Cohort Study.

Concerns have been raised that glucagon-like peptide 1 receptor agonists (GLP1-RAs) may increase the risk of thyroid cancer, but evidence remains conflicting. We therefore investigated if GLP1-RA use, compared with use of dipeptidyl peptidase-4 inhibitors (DPP-4is), was associated with thyroid cancer risk in patients with type 2 diabetes. This multisite cohort study with subsequent meta-analysis included six population-based databases from Canada (Ontario), Denmark, Norway, South Korea, Sweden, and Taiwan.

Encapsulation of Nanocrystals in Mannitol-Based Inhalable Microparticles via Spray-Drying: A Promising Strategy for Lung Delivery of Curcumin.

Background/objectives: Curcumin is well known for its great anti-inflammatory and antioxidant efficacy, representing a potential strategy for the treatment of respiratory disorders. However, several drawbacks, such as chemical instability, poor water solubility and rapid metabolism, result in low bioavailability, limiting its clinical applications. In this study, curcumin nanocrystals were incorporated into mannitol-based microparticles to obtain an inhalable dry powder.

Genome of root celery and population genomic analysis reveal the complex breeding history of celery.

Celery (Apium graveolens L.) is an important vegetable crop in the Apiaceae family. It comprises three botanical varieties: common celery with solid and succulent petioles, celeriac or root celery with enlarged and fleshy hypocotyls and smallage or leaf celery with slender, leafy and usually hollow petioles.

Desorption of pharmaceutical hydrochlorides from transition metal oxide nanoparticles - investigation by capillary electrophoresis.

The binding affinity of pharmaceutical hydrochlorides onto transition metal oxide nanoparticles (TMONPs) was investigated through a consecutive process of adsorption and desorption. Mexiletine (MEX) was chosen as a model pharmaceutical hydrochloride that bound onto TMONPs' surface through electrostatic interactions and coordination bonding. Response surface methodology was applied for their optimal separation by capillary electrophoresis to achieve accurate quantitation.

Noncanonical role of ALAS1 as a heme-independent inhibitor of small RNA-mediated silencing.

microRNAs (miRNAs) and small interfering RNAs (siRNAs) are 21- to 22-nucleotide RNAs that guide Argonaute-class effectors to targets for repression. In this work, we uncover 5-aminolevulinic acid synthase 1 (ALAS1), the initiating enzyme for heme biosynthesis, as a general repressor of miRNA accumulation. Although heme is known to be a positive cofactor for the nuclear miRNA processing machinery, ALAS1-but not other heme biosynthesis enzymes-limits the assembly and activity of Argonaute complexes under heme-replete conditions.

Lithium Use During Pregnancy in 14 Countries.

Importance: In pregnancy, the benefits of lithium treatment for relapse prevention in psychiatric conditions must be weighed against potential teratogenic effects. Currently, there is a paucity of information on how and when lithium is used by pregnant women.

Objective: To examine lithium use in the perinatal period.

Comparison of Intraoperative Fentanyl Usage and Waste After Transition from 100-μg Vials to 50-μg Preloaded Syringes: A Single-Center Retrospective Study.

Background: The rapidly acting opioid fentanyl commonly used in the perioperative setting, has traditionally been packaged in 100 or 250-μg vials. In September 2021, our institution implemented a change from fentanyl 100-μg vials to 50-μg preloaded syringes in our operating rooms. The objective of this study was aimed at assessing the association of the fentanyl product change on reducing medication waste and the amount of fentanyl administered during surgery.

Development and Validation of Prognostic Model for Metastatic Castration-Resistant Prostate Cancer Patients Treated With First-Line Abiraterone or Enzalutamide.

Introduction: Over the years, several prognostic models were developed in patients receiving chemotherapy for metastatic castration resistant prostate cancer (mCRPC), while data on androgen-receptor signaling inhibitors (ARSI) in a real-world setting are limited.

Patients And Methods: We compared a consecutive series of 565 mCRPC patients receiving first-line ARSI at 4 high-volume Italian Centers (development set) to an external series of 180 patients receiving the same treatment at another Italian high-volume Center (training set), between 2011 and 2022. Sixteen clinical and baseline laboratory variables were selected to develop a prognostic model.

Design and Bottom-up Production of an Aerosolizable Cannabidiol Nanosuspension.

Cannabidiol (CBD), a small nonpsychoactive molecule derived from , exerts a variety of therapeutic actions, such as anti-inflammatory, antioxidant, and antibacterial. Epidiolex is the only FDA-approved medicine containing pure CBD as an oral solution for seizure-controlling therapy. Nevertheless, the oral bioavailability of CBD is challenging due to its physical-chemical properties such as low solubility in water and high first-pass metabolism.

Safety and effectiveness of methylphenidate ER multi-unit pellet system in ADHD patients: An open label study.

Background: Attention deficit hyperactive disorder (ADHD) is a neurodevelopmental disorder occurring in children and adults. Pharmacotherapy remains the cornerstone of ADHD treatment. Stimulants such as methylphenidate are effective and have been one of the best studied and most frequently used treatment for ADHD.

Mapping the microRNA landscape in the older adult brain and its genetic contribution to neuropsychiatric conditions.

MicroRNAs (miRNAs) play a crucial role in regulating gene expression and influence many biological processes. Despite their importance, understanding of how genetic variation affects miRNA expression in the brain and how this relates to brain disorders remains limited. Here we investigated these questions by identifying microRNA expression quantitative trait loci (miR-QTLs), or genetic variants associated with brain miRNA levels, using genome-wide small RNA sequencing profiles from dorsolateral prefrontal cortex samples of 604 older adult donors of European ancestry.

Parent coaching to target language outcomes for Chinese-learning autistic preschoolers: A preliminary study.

Purpose: The present study evaluates the preliminary effectiveness of a parent-implemented support program to enhance language outcomes in Chinese-learning preschoolers with a confirmed diagnosis or at elevated likelihood of autism, a lifelong neurodevelopmental condition. The program is delivered entirely online with the option of a group format. Because of cross-cultural differences in adult learning and parent-child interaction and because parent coaching programs for autism that are delivered online are only emerging, a specific study to evaluate the effectiveness of online support for Chinese families is warranted.

Early onset metastatic colorectal cancer patients as a distinctive clinical and molecular phenomenon.

Background: Despite a reduction of both incidence and mortality from CRC, recent studies have shown an increase in the incidence of early-onset CRC (EO-CRC). Data on this setting are limited. The aim of our study was to evaluate the clinical and molecular profiles of metastatic EO-CRC patients in order to identify differences compared to a late-onset CRC (LO-CRC) control group.

Fall risk-increasing drugs and associated health outcomes among community-dwelling older patients: A cross-sectional study in Croatian cohort of the EuroAgeism H2020 project.

Our study aimed to assess the prevalence of fall risk-increasing drugs (FRIDs) in a sample of community-residing older patients in Croatia and its association with negative health outcomes. An observational, cross-sectional study was conducted on older patients (65+) visiting community pharmacies in three regionally different study sites in Croatia. Data were collected using a questionnaire developed for that purpose and included components of comprehensive geriatric assessment.