The trait-specific timing of accelerated genomic change in the human lineage.

Humans exhibit distinct characteristics compared to our primate and ancient hominin ancestors. To investigate genomic bursts in the evolution of these traits, we use two complementary approaches to examine enrichment among genome-wide association study loci spanning diseases and AI-based image-derived brain, heart, and skeletal tissue phenotypes with genomic regions reflecting four evolutionary divergence points. These regions cover epigenetic differences among humans and rhesus macaques, human accelerated regions (HARs), ancient selective sweeps, and Neanderthal-introgressed alleles.

Deep learning based phenotyping of medical images improves power for gene discovery of complex disease.

Electronic health records are often incomplete, reducing the power of genetic association studies. For some diseases, such as knee osteoarthritis where the routine course of diagnosis involves an X-ray, image-based phenotyping offers an alternate and unbiased way to ascertain disease cases. We investigated this by training a deep-learning model to ascertain knee osteoarthritis cases from knee DXA scans that achieved clinician-level performance.

The genetic architecture and evolution of the human skeletal form.

The human skeletal form underlies bipedalism, but the genetic basis of skeletal proportions (SPs) is not well characterized. We applied deep-learning models to 31,221 x-rays from the UK Biobank to extract a comprehensive set of SPs, which were associated with 145 independent loci genome-wide. Structural equation modeling suggested that limb proportions exhibited strong genetic sharing but were independent of width and torso proportions.

Observation of high-energy neutrinos from the Galactic plane.

The origin of high-energy cosmic rays, atomic nuclei that continuously impact Earth's atmosphere, is unknown. Because of deflection by interstellar magnetic fields, cosmic rays produced within the Milky Way arrive at Earth from random directions. However, cosmic rays interact with matter near their sources and during propagation, which produces high-energy neutrinos.

The genetic architecture of the human skeletal form.

The human skeletal form underlies our ability to walk on two legs, but unlike standing height, the genetic basis of limb lengths and skeletal proportions is less well understood. Here we applied a deep learning model to 31,221 whole body dual-energy X-ray absorptiometry (DXA) images from the UK Biobank (UKB) to extract 23 different image-derived phenotypes (IDPs) that include all long bone lengths as well as hip and shoulder width, which we analyzed while controlling for height. All skeletal proportions are highly heritable (∼40-50%), and genome-wide association studies (GWAS) of these traits identified 179 independent loci, of which 102 loci were not associated with height.

Strong Constraints on Neutrino Nonstandard Interactions from TeV-Scale ν_{μ} Disappearance at IceCube.

We report a search for nonstandard neutrino interactions (NSI) using eight years of TeV-scale atmospheric muon neutrino data from the IceCube Neutrino Observatory. By reconstructing incident energies and zenith angles for atmospheric neutrino events, this analysis presents unified confidence intervals for the NSI parameter ε_{μτ}. The best-fit value is consistent with no NSI at a p value of 25.

Search for Relativistic Magnetic Monopoles with Eight Years of IceCube Data.

We present an all-sky 90% confidence level upper limit on the cosmic flux of relativistic magnetic monopoles using 2886 days of IceCube data. The analysis was optimized for monopole speeds between 0.750c and 0.

[Influenza vaccination: pros and cons? Views of general practitioners and the general population].

Unlabelled: Összefoglaló. Bevezetés: A magyar felnőtt lakosság heterogén attitűdje folytán az influenza elleni átoltottság elmarad az nemzetközi ajánlásoktól. A háziorvosok meggyőző potenciálja jelentős, ezért fontos szerepük van a felnőtt lakosság oltással kapcsolatos döntéseinek befolyásolásában.

MEK inhibitor resistance mechanisms and recent developments in combination trials.

The mitogen-activated protein kinase (MAPK) pathway plays a vital role in cellular processes such as gene expression, cell proliferation, cell survival, and apoptosis. Also known as the RAS-RAF-MEK-ERK pathway, the MAPK pathway has been implicated in approximately one-third of all cancers. Mutations in RAS or RAF genes such as KRAS and BRAF are common, and these mutations typically promote malignancies by over-activating MEK and ERK downstream, which drives sustained cell proliferation and uninhibited cell growth.

The Role of GDF15 in Regulating the Canonical Pathways of the Tumor Microenvironment in Wild-Type p53 Ovarian Tumor and Its Response to Chemotherapy.

Background: The standard treatment of ovarian cancer is surgery followed by a chemotherapeutic combination consisting of a platinum agent, such as cisplatin and a taxane-like paclitaxel. We previously observed that patients with ovarian cancer wild-type for had a poorer survival rate than did those with mutations. Thus, a better understanding of the molecular changes of epithelial ovarian cancer cells with wild-type in response to treatment with cisplatin could reveal novel mechanisms of chemoresistance.

Clay-Polymer Nanocomposites Prepared by Reactive Melt Extrusion for Sustained Drug Release.

Clay-polymer nanocomposites have exhibited a great potential as carriers for controlled release drug delivery. This study aims to prepare exfoliated montmorillonite-Eudragit RS nanocomposites using reactive melt extrusion and investigate the influence of claying loading, clay types (sodium montmorillonite (Cloisite Na) vs. organomodified montmorillonite (Cloisite 20)) on clay-polymer interactions and drug release properties.

[Vaccine hesitancy among primary healthcare professionals in Hungary].

The attitude to immunization and the issue of vaccine hesitancy in health care workers (HCWs) have been studied in a former survey performed by ECDC (European Centre for Disease Prevention and Control). Our aim was to study the immunization attitude of primary care paediatricians, general practitioners and primary care nurses in Hungary. : We studied vaccine hesitancy in HCWs by way of a questionnaire, developed on the basis of a recent similar survey by ECDC in four countries.

[Infrequent systemic drug interaction: repeated syncope caused by combined treatment with timolol-containing eye drops and lercanidipine tablet].

The control and planning of the treatment of hypertensive patients need specific attention. As regards concomitant diseases and treatments, glaucoma and the use of eye drops should be taken into consideration. The ingredients of the administered eye drops get through the nasolacrimal canal and can be absorbed by the nasal mucosa.

[Patient Journey in Schizophrenia - Lessons of a Hungarian Survey].

The disorder-related experiences of schizophrenic patients are an important basis for personalized treatment. This illness experience is now described with the concept of patient journey. The patient journey shows how the symptoms and treatment interfere with the patient's personal existence and how they affect the optimal functionality.

Clinical presentation, treatment and outcome of Takayasu's arteritis in southern Chinese: a multicenter retrospective study.

To study the clinical presentation, treatment and outcome of southern Chinese patients with Takayasu's arteritis (TA). This is a retrospective chart review study of 78 patients managed in 14 public hospitals in Hong Kong between the years 2000 and 2010. Patients were identified from the hospital registry using the ICD-10 diagnostic code of the disease.

Effect of Achieving Minimal Disease Activity on the Progression of Subclinical Atherosclerosis and Arterial Stiffness: A Prospective Cohort Study in Psoriatic Arthritis.

Objective: To investigate the effects of achieving minimal disease activity (MDA) on the progression of subclinical atherosclerosis and arterial stiffness in patients with psoriatic arthritis (PsA).

Methods: A total of 101 consecutive patients with PsA were recruited for this prospective cohort study. All patients received protocolized treatment targeting MDA for a period of 2 years.

Bone Mass, Microstructure, and Strength Can Discriminate Vertebral Fracture in Patients on Long-Term Steroid Treatment.

Context: Measurement of areal bone mineral density (aBMD) by dual-energy x-ray absorptiometry (DXA) was able to predict fracture risk. High-resolution peripheral quantitative computed tomography (HR-pQCT) yields additional information about volumetric bone mineral density (vBMD), microarchitecture, and strength that may increase our understanding of fracture susceptibility.

Objective: To ascertain whether vBMD, microarchitecture, and estimated bone strength derived from HR-pQCT can discriminate vertebral fractures in patients with glucocorticoid-induced osteoporosis (GIOP) independent of aBMD.

Influence of lidocaine forms (salt vs. freebase) on properties of drug-eudragit® L100-55 extrudates prepared by reactive melt extrusion.

This study examines the preparation of sustained-release lidocaine polyelectrolyte complex using reactive melt extrusion. Eudragit L100-55 was selected as the ionic polymer. The influence of drug forms (freebase vs.

Effect of Treat-to-target Strategies Aiming at Remission of Arterial Stiffness in Early Rheumatoid Arthritis: A Randomized Controlled Study.

Objective: To determine the efficacy of 2 tight control treatment strategies aiming at Simplified Disease Activity Score (SDAI) remission (SDAI ≤ 3.3) compared to 28-joint count Disease Activity Score (DAS28) remission (DAS28 < 2.6) in the prevention of arterial stiffness in patients with early rheumatoid arthritis (RA).