Reanalysis of Urothelial Cancer Chemoimmunotherapy Trials With Differential Censoring.

Importance: Three similar phase 3 randomized clinical trials have investigated PD-1/PD-L1 (programmed cell death 1 protein/programmed cell death 1 ligand 1) inhibitors in combination with platinum-based chemotherapy vs chemotherapy alone as first-line treatment for advanced urothelial carcinoma (IMvigor130, atezolizumab; KEYNOTE-361, pembrolizumab; and CheckMate901, nivolumab). Only CheckMate901 reported overall survival (OS) benefit for the combination. The reason for these inconsistent results is unclear.

Depressive Symptoms and Amyloid Pathology.

Importance: Depressive symptoms are associated with cognitive decline in older individuals. Uncertainty about underlying mechanisms hampers diagnostic and therapeutic efforts. This large-scale study aimed to elucidate the association between depressive symptoms and amyloid pathology.

Polygenic Risk Score Added to Conventional Case Finding to Identify Undiagnosed Chronic Obstructive Pulmonary Disease.

Importance: Chronic obstructive pulmonary disease (COPD) is often undiagnosed. Although genetic risk plays a significant role in COPD susceptibility, its utility in guiding spirometry testing and identifying undiagnosed cases is unclear.

Objective: To determine whether a COPD polygenic risk score (PRS) enhances the identification of undiagnosed COPD beyond a case-finding questionnaire (eg, the Lung Function Questionnaire) using conventional risk factors and respiratory symptoms.

Novel pain management strategy for uterine fibroid embolization.

Background: Uterine fibroid embolization can be associated with significant pain due to fibroid ischemia and interventions of the procedure itself. Fentanyl and midazolam are commonly provided for sedation and pain relief, but are not tolerated by all patients. This report outlines a novel pain management strategy for uterine fibroid embolization in a patient who could not receive either opioids or benzodiazepines.

Attenuated cardiac autonomic function in patients with long-COVID with impaired orthostatic hemodynamics.

Purpose: Long-coronavirus disease (long-COVID) is associated with initial orthostatic hypotension and postural orthostatic tachycardia syndrome. Whether altered autonomic tone underlies these abnormalities is unknown. We compared autonomic function between patients with long-COVID and healthy controls, and within patients with long-COVID with different orthostatic hemodynamic phenotypes.

The Use of Bone Biomarkers, Imaging Tools, and Genetic Tests in the Diagnosis of Rare Bone Disorders.

Rare bone diseases are clinically and genetically heterogenous. Despite those differences, the underlying pathophysiology is not infrequently different. Several of these diseases are characterized by abnormal bone metabolism and turnover with subsequent abnormalities in markers of bone turnover, rendering them useful adjuncts in the diagnostic process.

Primary diffuse leptomeningeal atypical teratoid/rhabdoid tumours (ATRT) of childhood: a molecularly characterised case report and literature review.

Background: Atypical teratoid/rhabdoid tumours (ATRTs) are malignant central nervous system tumours, typically presenting in the posterior fossa of very young children. Prognosis remains poor despite current therapy, while tumorigenesis implicates both genomic and epigenetic dysregulation. Primary diffuse leptomeningeal (PDL) ATRT, characterised by the absence of an intraparenchymal mass lesion, is seldom reported but appears associated with a dismal outcome.

The arabidopsis phytoglobin 1 (Pgb1) involvement in somatic embryogenesis is linked to changes in ethylene and the class VII ethylene transcription factor HRE2.

Phytoglobin1 promotes Arabidopsis somatic embryogenesis through the mediation of ethylene and the ERFVII HRE2. Generation of somatic embryos in Arabidopsis (Arabidopsis thaliana) is a two-step process, encompassing an induction phase where embryogenic tissue (ET) is formed followed by a developmental phase encouraging the growth of the embryos. Using previously characterized transgenic lines dysregulating the class 1 Phytoglobin (Pgb1) we show that suppression of Pgb1 decreases somatic embryogenesis (SE).

The anti-dyskinetic effect of the clinic-ready mGluRpositive allosteric modulator AZD8529 in the 6-OHDA-lesioned rat.

L-3,4-dihydroxyphenylalanine (L-DOPA) remains the main treatment for motor symptoms of Parkinson's disease (PD). However, chronic use is associated with the development of complications such as L-DOPA-induced dyskinesia. We previously demonstrated that LY-487,379, a highly selective metabotropic glutamate receptor 2 (mGluR2) positive allosteric modulator (PAM), reduces the severity of L-DOPA-induced abnormal involuntary movements (AIMs) in the 6-hydroxydopamine (6-OHDA)-lesioned rat model of PD, without interfering with the anti-parkinsonian action of L-DOPA.

The association between pain, analgesia, and delirium among critically ill adults: a systematic review and meta-analysis.

Purpose: We performed a systematic review with meta-analysis examining the relationship between pain or pain medications and delirium occurence, duration, and severity.

Methods: We searched MEDLINE, EMBASE, CINAHL and the Cochrane Central Register of Controlled Trials from inception to May 15, 2023. We included randomised or observational studies among critically ill adults, that reported data on pain or exposure to analgesics, and reported delirium presence, duration, or severity with no language or region restrictions.

A dihydrochalcone-specific O-methyltransferase from leaf buds of Populus trichocarpa implicated in bud resin formation.

Production of secreted leaf bud resin is a mechanism for temperate trees to protect dormant leaf buds against frost damage, dehydration, and insect herbivory. Bud resins contain a wide variety of special metabolites including terpenoids, benzenoids, and phenolics. The leaf bud resins of Populus trichocarpa and P.

Divergence in genetic (co)variances and the alignment of gmax with phenotypic divergence.

To better understand the sources of biological diversity in nature, we need information on the mechanisms underlying population divergence. Biological systems with patterns of naturally occurring adaptive variation among populations can provide insight into the genetic architecture of diverging traits and the influence of genetic constraints on responses to selection. Using a system of reproductive character displacement in the North American mushroom-feeding fly Drosophila subquinaria, we assessed patterns of genetic (co)variance among a suite of chemical signaling traits and divergence in this pattern among populations.

A systematic review to determine the effect of strategies to sustain chronic disease prevention interventions in clinical and community settings.

This review assessed the effect of strategies designed to sustain the delivery of evidenced based interventions (EBIs) which target behavioural risk factors linked to leading causes of chronic disease in clinical and community settings. Seven electronic databases were searched for randomised controlled studies published from earliest record to November 2022. Studies were included if they tested a strategy to sustain the delivery of an EBI within clinical or community settings.

The role of alternative oxidase in the maintenance of cellular redox balance under hypoxia via participation in nitric oxide turnover.

Alternative oxidase (AOX) regulates the level of reactive oxygen species and nitric oxide (NO) in plants. While under normoxic conditions it alleviates NO formation, there are several indications that in the conditions of low oxygen such as during seed germination before radicle protrusion, in meristematic stem cells, and in flooded roots AOX can be involved in the production of NO from nitrite. Whereas the first reports considered this role as indirect, more evidence is accumulated that AOX can act as a nitrite: NO reductase.

Dual ligand functionalized pH-sensitive liposomes for metastatic breast cancer treatment: and assessment.

This research demonstrates the design and development of a novel dual-targeting, pH-sensitive liposomal (pSL) formulation of 5-Fluorouracil (5-FU), , (5-FU-iRGD-FA-pSL) to manage breast cancer (BC). The motivation to explore this formulation is to overcome the challenges of systemic toxicity and non-specific targeting of 5-FU, a conventional chemotherapeutic agent. The proposed formulation also combines folic acid (FA) and iRGD peptides as targeting ligands to enhance tumor cell specificity and penetration, while the pH-sensitive liposomes ensure the controlled drug release in the acidic tumor microenvironment.

A double dissociation between semantic and spatial cognition in visual to default network pathways.

Processing pathways between sensory and default mode network (DMN) regions support recognition, navigation, and memory but their organisation is not well understood. We show that functional subdivisions of visual cortex and DMN sit at opposing ends of parallel streams of information processing that support visually mediated semantic and spatial cognition, providing convergent evidence from univariate and multivariate task responses, intrinsic functional and structural connectivity. Participants learned virtual environments consisting of buildings populated with objects, drawn from either a single semantic category or multiple categories.

Effect of repeated sprint training in hypoxia on acute and chronic redox balance modulation.

Little is known regarding the effects high-intensity training performed in hypoxia on the oxidative stress and antioxidant systems. The aim of this study was to assess the potential effect of 4 weeks of repeated sprint training in hypoxia (RSH) on the redox balance. Forty male well-trained cyclists were matched into two different interventions (RSH,  = 20) or in normoxia, RSN,  = 20) and tested twice (before (Pre-) and after (Post-) a 4-week of training) for performance (repeated sprint ability (RSA) test), oxidative stress, and antioxidant status.

Evaluation of the effect of 2-borneol on the model through oxidative stress and acute toxicity tests.

Borneol, a compound found in resin-rich plants, is known for its aromatic and therapeutic properties. Widely used in countries, such as China, Japan, and Southeast Asia, borneol has also demonstrated efficacy in nanodrug administration. The primary objective of this study is to understand how borneol induces oxidative stress, its impact on the attraction and repulsion of , and its acute toxicity.

The Relationships Between Body-Related Emotion Intolerance and Restrictive Eating as a Function of Multidimensional Perfectionism.

Objective: Emotion intolerance and perfectionism are two maintaining mechanisms to eating disorder symptomology. However, it is unclear how these mechanisms relate to one another. This study explored whether perfectionism is a vulnerability factor for facets of restrictive eating in the context of body-related emotions.

Associations Between Coparenting Quality, the Home Food Environment, and Child's Body Mass Index.

Although positive coparenting, or how parents relate during childrearing, is known to support children's socioemotional development, the role of coparenting in supporting children's healthy eating and growth is poorly understood. This study examined associations between coparenting quality, the home food environment, and young children's body mass index (BMI). Cross-sectional data were obtained from 290 mothers and their 3-year-old children who participated in the Sprout study.

Tracking Physical Activity and Nutrition Policies and Practices in Early Childhood Education and Care: Five Years Post-Implementation of a Provincial-Level Active Play Standard.

Early childhood education and care (ECEC) settings are key for improving health behaviors, including physical activity (PA) and nutrition. In 2017, the province of British Columbia (BC) implemented a provincial-level Active Play policy supported by a capacity-building intervention. Significant improvements in all PA policies and practices and the majority of nutrition policies were observed post-implementation.

FLT3 is genetically essential for ITD-mutated leukemic stem cells but dispensable for human hematopoietic stem cells.

Leukemic stem cells (LSCs) fuel acute myeloid leukemia (AML) growth and relapse, but therapies tailored towards eradicating LSCs without harming normal hematopoietic stem cells (HSCs) are lacking. FLT3 is considered an important therapeutic target due to frequent mutation in AML and association with relapse. However, there has been limited clinical success with FLT3 drug targeting, suggesting either that FLT3 is not a vulnerability in LSC, or that more potent inhibition is required, a scenario where HSC toxicity could become limiting.

Evaluation of antimicrobial susceptibility testing methods for complex isolates from people with and without cystic fibrosis.

The complex (BCC) is a group of Gram-negative bacteria that cause opportunistic infections, most notably in people with cystic fibrosis (CF), and have been associated with outbreaks caused by contaminated medical products. Antimicrobial susceptibility testing (AST) is often used to guide treatment for BCC infections, perhaps most importantly in people with CF who are being considered for lung transplant. However, recent studies have highlighted problems with AST methods.