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The TWIK-related acid-sensitive K+ channel 3 (TASK3) belongs to the two-pore domain (K2P) potassium channel family, which regulates cell excitability by mediating a constitutive "leak" potassium efflux in the nervous system. Extracellular acidification inhibits TASK3 channel, but the molecular mechanism by which channel inactivation is coupled to pH decrease remains unclear. Here, we report the cryo-electron microscopy structures of human TASK3 at neutral and acidic pH. Structural comparison revealed selectivity filter (SF) rearrangements upon acidification, characteristic of C-type inactivation, but with a unique structural basis...

Characterizing the relationship between disease testing behaviors and infectious disease dynamics is of great importance for public health. Tests for both current and past infection can influence disease-related behaviors at the individual level, while population-level knowledge of an epidemic's course may feed back to affect one's likelihood of taking a test. The COVID-19 pandemic has generated testing data on an unprecedented scale for tests detecting both current infection (PCR, antigen) and past infection (serology); this opens the way to characterizing the complex relationship between testing behavior and infection dynamics...

We present an experiment on the immediate and lasting effects of reminder nudges in a complex environment. In the study, 1,542 subjects face a setting where, within a brief time frame, they have to pay attention to and perform multiple actions in a computer game. The experiment investigates i) the effect of reminders on the reminded actions and their spillovers on nonreminded actions; ii) spillovers between multiple nudges when the number of reminded actions is increased; and iii) intertemporal spillovers from having been exposed to reminders on actions after reminders are withdrawn...

Improving equity in undergraduate STEM is a national imperative. Although there is a rapidly growing body of research in this area, there is still a need to generate empirical evidence for equitable teaching techniques. We ground our work in Complex Instruction, an extensively researched pedagogical approach based on sociological theories and the malleability of status. This approach has been applied primarily in K-12 classrooms. In this manuscript, we explore the application of one strategy from Complex Instruction-assigning competence-to undergraduate STEM classrooms...

Diabetes mellitus adversely affects the contractile ability of the small intestine. However, there is a paucity of studies investigating the impact of garlic oil on small intestinal motility. This study aimed to evaluate the potential beneficial effects of garlic oil on type 2 diabetes mellitus in rats. Thirty-six adult female Wistar rats (n = 36) were divided into four groups: control, non-diabetic rats supplemented with garlic oil, diabetic rats, and diabetic rats treated with garlic oil. The rats were anesthetized using pentobarbitone (40 mg/kg BW); various motility parameters and oxidative markers were determined in small intestinal segments...

BACKGROUND: Observational evidence suggests the 4CMenB meningococcal vaccine may partially protect against gonorrhea, with one dose being two-thirds as protective as two. We examined the cost-effectiveness of vaccinating men-who-have-sex-with-men (MSM) in England, with one- or two-dose primary vaccination. METHODS: Integrated transmission-dynamic health-economic modeling explored the effects of targeting strategy, first- and second-dose uptake levels, and duration of vaccine protection, using observational estimates of vaccine protection...

ZCCHC17 is a master regulator of synaptic gene expression and has recently been shown to play a role in splicing of neuronal mRNA. We previously showed that ZCCHC17 protein declines in Alzheimer's disease (AD) brain tissue before there is significant gliosis and neuronal loss, that ZCCHC17 loss partially replicates observed splicing abnormalities in AD brain tissue, and that maintenance of ZCCHC17 levels is predicted to support cognitive resilience in AD. Here, we assessed the functional consequences of reduced ZCCHC17 expression in primary cortical neuronal cultures using siRNA knockdown...

BACKGROUND: Current tobacco smoking is independently associated with decreased overall survival (OS) among patients with metastatic renal cell carcinoma (mRCC) treated with targeted monotherapy (VEGF-TKI). Herein, we assess the influence of smoking status on the outcomes of patients with mRCC treated with the current first-line standard of care of immune checkpoint inhibitor (ICI)-based regimens. MATERIALS AND METHODS: Real-world data from the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) were collected retrospectively...

IMPORTANCE: Autism spectrum disorder (ASD) is a neurodevelopmental disorder more prevalent in males than in females. The cause of ASD is largely genetic, but the association of genetics with the skewed sex ratio is not yet understood. To our knowledge, no large population-based study has provided estimates of heritability by sex. OBJECTIVE: To estimate the sex-specific heritability of ASD. DESIGN, SETTING, AND PARTICIPANTS: This was a population-based, retrospective analysis using national health registers of nontwin siblings and cousins from Sweden born between January 1, 1985, and December 31, 1998, with follow-up to 19 years of age...

IMPORTANCE: Unlike medications, procedural interventions are rarely trialed against placebo prior to becoming accepted in clinical practice. When placebo-controlled trials are eventually conducted, procedural interventions may be less effective than previously believed. OBJECTIVE: To investigate the importance of including a placebo arm in trials of surgical and interventional procedures by comparing effect sizes from trials of the same procedure that do and do not include a placebo arm...

IMPORTANCE: Treatment of erythema and flushing in rosacea is challenging. Calcitonin gene-related peptide (CGRP) has been associated with the pathogenesis of rosacea, raising the possibility that inhibition of the CGRP pathway might improve certain features of the disease. OBJECTIVE: To examine the effectiveness, tolerability, and safety of erenumab, an anti-CGRP-receptor monoclonal antibody, for the treatment of rosacea-associated erythema and flushing. DESIGN, SETTING, AND PARTICIPANTS: This single-center, open-label, single-group, nonrandomized controlled trial was conducted between June 9, 2020, and May 11, 2021...

Herein, we have investigated the unexplored thermoelectric properties of Zintl-phase KCaBi using first-principles calculation and the solution of the Boltzmann transport equation. KCaBi shows intrinsically very low lattice thermal conductivities ( κ l ) along the ( x ( y ), and z )-directions of (1.78, 0.68) and (1.15, 0.43) W m-1 K-1 at 300 and 800 K, respectively. Along with the effect of very low κ l , the high figure of merit ( ZT ) for p-type KCaBi results from the high Seebeck coefficients ( S ) and optimal electrical conductivities ( σ ), which originate from the high and steep total density of state (TDOS) at the valence band edge and the less dispersed multi-valley nature of the valence band edge in the band structure...

PURPOSE: Diversity, equity, and inclusion (DEI) have become an important priority for academic medicine. However, several barriers challenge the effective implementation of DEI-related pedagogy. An exploration of the barriers to and enablers of DEI-related pedagogy-as they relate to professional contexts-can inform how to advance DEI in medical education. Shulman's notion of signature pedagogies offers a foundation for understanding and exploring the influence of such contexts on teaching and learning...

ConspectusImplantable neurotechnology enables monitoring and stimulating of the brain signals responsible for performing cognitive, motor, and sensory tasks. Electrode arrays implanted in the brain are increasingly used in the clinic to treat a variety of sources of neurological diseases and injuries. However, the implantation of a foreign body typically initiates a tissue response characterized by physical disruption of vasculature and the neuropil as well as the initiation of inflammation and the induction of reactive glial states...

Porous solids with highly microporous structures for effective carbon dioxide uptake and separation from mixed gases are highly desirable. Here we present the use of polyethylene glycol (20,000 g/mol) as a soft template for the simple and rapid synthesis of a highly microporous Cu-BTC (denoted as HKUST-1). The polyethylene glycol-templated HKUST-1 obtained at room temperature in 10 min exhibited a very high Brunauer-Emmett-Teller (BET) surface area of 1904 m2 /g, pore volume of 0.87 cm3 /g, and average micropore size of 0...

PURPOSE: The impact of age on optimal management of glioblastoma remains unclear. A recent combined analysis of two randomised trials, GEINO14-01 and EX-TEM, found no benefit from extending post-radiation temozolomide in newly diagnosed glioblastoma. Here, we explore the impact of age. METHODS: Relevant intergroup statistics were used to identify differences in tumour, treatment and outcome characteristics based on age with elderly patients (EP) defined as age 65 years and over...

INTRODUCTION: Patients with pediatric low-grade gliomas (pLGGs), the most common primary brain tumors in children, can often benefit from MAPK inhibitor (MAPKi) treatment. However, rapid tumor regrowth, also referred to as rebound growth, may occur once treatment is stopped, constituting a significant clinical challenge. METHODS: Four patient-derived pediatric glioma models were investigated to model rebound growth in vitro based on viable cell counts in response to MAPKi treatment and withdrawal...

PURPOSE: To investigate sex-related differences in the clinical presentation of multiple system atrophy (MSA) through a literature review and an analysis of a retrospective cohort. METHODS: The PubMed database was searched for articles including sex-related information in MSA. In a retrospective Innsbruck cohort, we investigated the baseline to last available follow-up clinical-demographic differences between men and women with MSA in a univariate fashion, followed by multivariable binary regression analysis...

Chronic, non-communicable diseases present a major barrier to living a long and healthy life. In many cases, early diagnosis can facilitate prevention, monitoring, and treatment efforts, improving patient outcomes. There is therefore a critical need to make screening techniques as accessible, unintimidating, and cost-effective as possible. The association between ocular biomarkers and systemic health and disease (oculomics) presents an attractive opportunity for detection of systemic diseases, as ophthalmic techniques are often relatively low-cost, fast, and non-invasive...

In this study, the degree of accumulation of biogenic element and heavy metal contents of different parts and edible layers of leeks cultivated in Konya in Turkey was revealed. The amounts of P and K of leek were determined from 154.69 (leaf top of leek) and 985.05 mg/kg (root of leek) to 1377.63 (onion part of leek) and 2688.50 mg/kg (root of leek), respectively. P and K contents of leek layers changed from 139.45 (1st layer) and 446.63 mg/kg (7th layer) to 1596.69 (2nd layer) and 2201.53 mg/kg (4th layer), respectively...