Multi-Targeting Macrocyclic Peptides as Nanomolar Inhibitors of Self- and Cross-Seeded Amyloid Self-Assembly of α-Synuclein.

Amyloid self-assembly of α-synuclein (αSyn) is linked to the pathogenesis of Parkinson's disease (PD). Type 2 diabetes (T2D) has recently emerged as a risk factor for PD. Cross-interactions between their amyloidogenic proteins may act as molecular links.

ECG-Gated Cardiac Multidetector CT Evaluation of the Normal Pulmonary Valve and Right Ventricular Outflow Tract in Dogs.

With the advancement in imaging technology, ECG-gated cardiac multidetector computed tomography (MDCT) has emerged as a tool for the anatomic evaluation of the pulmonary valve and right ventricular outflow tract (RVOT) in human medicine. Currently, the evaluation of the pulmonary valve relies primarily on echocardiographic examination. However, the bi-dimensional nature of this technique and the location/orientation of the pulmonary valve in the thoracic cavity can pose challenges.

Lanmodulin-Decorated Microbes for Efficient Lanthanide Recovery.

Rare earth elements (REEs) are essential for many clean energy technologies. Yet, they are a limited resource currently obtained through carbon-intensive mining. Here, bio-scaffolded proteins serve as simple, effective materials for the recovery of REEs.

Atypical Atrial Flutter: Electrophysiological Characterization and Effective Catheter Ablation.

Atrial flutter (AFL), defined as macro-re-entrant atrial tachycardia, is associated with debilitating symptoms, stroke, heart failure, and increased mortality. AFL is classified into typical, or cavotricuspid isthmus (CTI)-dependent, and atypical, or non-CTI-dependent. Atypical AFL is a heterogenous group of re-entrant atrial tachycardias that most commonly occur in patients with prior heart surgery or catheter ablation.

Reversal of Roux-en-Y Gastric Bypass: A Multi-Centric Analysis of Indications, Techniques, and Surgical Outcomes.

Background: Roux-en-Y gastric bypass may present long-term complications that require revisional surgery or even reversal to normal anatomy. Data on the indications, surgical technique, and outcomes of RYGB reversal remain scarce.

Methods: We identified 48 cases of RYGB reversals with complete 90-day follow-up within a multi-centric international retrospective database of elective secondary bariatric surgery.

Chronic Endometritis and Endometriosis: Two Sides of the Same Coin?

Both chronic endometritis and endometriosis are common entities in infertile patients. The association and the co-existence of these two entities are poorly evaluated. The aim of this systematic review and meta-analysis was to examine the association between chronic endometritis and endometriosis and to find the prevalence of chronic endometritis in women with endometriosis.

Predicting work ability impairment in post COVID-19 patients: a machine learning model based on clinical parameters.

The Post COVID-19 condition (PCC) is a complex disease affecting health and everyday functioning. This is well reflected by a patient's inability to work (ITW). In this study, we aimed to investigate factors associated with ITW (1) and to design a machine learning-based model for predicting ITW (2) twelve months after baseline.

Improving timing resolution of BGO for TOF-PET: a comparative analysis with and without deep learning.

Background: The renewed interest in BGO scintillators for TOF-PET is driven by the improved Cherenkov photon detection with new blue-sensitive SiPMs. However, the slower scintillation light from BGO causes significant time walk with leading edge discrimination (LED), which degrades the coincidence time resolution (CTR). To address this, a time walk correction (TWC) can be done by using the rise time measured with a second threshold.

Treatment of Venous Thromboembolism with Edoxaban over 18 Months: Results from ETNA-VTE Europe.

Background:  The benefits and risks of extending anticoagulant treatment beyond the first 3 to 6 months in patients with venous thromboembolism (VTE) in clinical practice are not well understood.

Methods:  ETNA-VTE Europe is a prospective, noninterventional, post-authorization study in unselected patients with VTE treated with edoxaban in eight European countries for up to 18 months. Recurrent VTE, major bleeding, and all-cause death were the primary study outcomes.

Individualization of piperacillin dosage based on therapeutic drug monitoring with or without model-informed precision dosing: a scenario analysis.

Background: Model-informed precision dosing (MIPD) combines population pharmacokinetic knowledge with therapeutic drug monitoring (TDM) to optimize dosage adjustment. It could improve target concentration attainment over empirical TDM, still widely practised for broad-spectrum antibiotics.

Objectives: To evaluate the respective performance of TDM and MIPD in achieving target piperacillin exposure.

Parosmia: Pathophysiology and Management.

Purpose Of Review: Parosmia is a qualitative olfactory disorder in which there is a mismatch between the memory of an odor and the actual experience triggered by an odor. There has been a surge in parosmia-related publications since the COVID-19 pandemic. This review summarizes the latest clinical findings, theories on pathophysiology and potential treatment options.

Locally Specific Genome-Wide Signatures of Adaptation to Environmental Variation at High Resolution in an Alpine Plant.

Microevolutionary processes shape adaptive responses to heterogeneous environments, where these effects vary both among and within species. However, it remains largely unknown to which degree signatures of adaptation to environmental drivers can be detected based on the choice of spatial scale and genomic marker. We studied signatures of local adaptation across two levels of spatial extents, investigating complementary types of genomic variants-single-nucleotide polymorphisms (SNPs) and polymorphic transposable elements (TEs)-in populations of the alpine model plant species Arabis alpina .

TRPM4 contributes to cell death in prostate cancer tumor spheroids, and to extravasation and metastasis in a zebrafish xenograft model system.

Transient receptor potential melastatin-4 (TRPM4) ion channel expression is upregulated in prostate cancer (PCa), contributing to increased cell proliferation, migration, adhesion, epithelial-to-mesenchymal transition, cell cycle shift, and alterations of intracellular Ca signaling. GEO2R platform analysis of messenger RNA (mRNA) expression of ~ 6350 genes in normal and malignant prostate tissue samples from 15 PCa patients demonstrates that TRPM4 expression is upregulated sixfold and is among the most significantly upregulated genes in PCa. We find that absence of TRPM4 reduced PCa tumor spheroid size and decreased PCa tumor spheroid outgrowth.

Phytonanoparticles as novel drug carriers for enhanced osteogenesis and osseointegration.

Phytonanoparticles have emerged as a promising class of biomaterials for enhancing bone regeneration and osseointegration, offering unique advantages in biocompatibility, multifunctionality, and sustainability. This comprehensive review explores the synthesis, characterization, and applications of phytonanoparticles in bone tissue engineering. The green synthesis approach, utilizing plant extracts as reducing and stabilizing agents, yields nanoparticles with intrinsic bioactive properties that can synergistically promote osteogenesis.

Brain-wide neuronal circuit connectome of human glioblastoma.

Glioblastoma (GBM) infiltrates the brain and can be synaptically innervated by neurons, which drives tumor progression. Synaptic inputs onto GBM cells identified so far are largely short-range and glutamatergic. The extent of GBM integration into the brain-wide neuronal circuitry remains unclear.

Sex-based analysis of status epilepticus management and outcome: A cohort study.

Status epilepticus (SE) is a neurological emergency with significant morbidity and mortality. The role of sex as a factor influencing the characteristics, treatment, and outcomes of SE has been scarcely addressed. This study investigates this variable regarding the clinical management and outcome among adult patients with SE.

Tests for diagnosis of postpartum haemorrhage at vaginal birth.

Background: Postpartum haemorrhage (PPH) is the leading cause of maternal mortality worldwide. Accurate diagnosis of PPH can prevent adverse outcomes by enabling early treatment.

Objectives: What is the accuracy of methods (index tests) for diagnosing primary PPH (blood loss ≥ 500 mL in the first 24 hours after birth) and severe primary PPH (blood loss ≥ 1000 mL in the first 24 hours after birth) (target conditions) in women giving birth vaginally (participants) compared to weighed blood loss measurement or other objective measurements of blood loss (reference standards)?

Search Methods: We searched CENTRAL, MEDLINE, Embase, Web of Science Core Collection, ClinicalTrials.

Microenvironmental Regulation of Dormancy in Breast Cancer Metastasis: "An Ally that Changes Allegiances".

Breast cancer remission after treatment is sometimes long-lasting, but in about 30% of cases, there is a relapse after a so-called dormant state. Cellular cancer dormancy, the propensity of disseminated tumor cells (DTCs) to remain in a nonproliferative state for an extended period, presents an opportunity for therapeutic intervention that may prevent reawakening and the lethal consequences of metastatic outgrowth. Therefore, identification of dormant DTCs and detailed characterization of cancer cell-intrinsic and niche-specific [i.

Hormone Signaling in Breast Development and Cancer.

Hormones control normal breast development and function. They also impinge on breast cancer (BC) development and disease progression in direct and indirect ways. The major ovarian hormones, estrogens and progesterone, have long been established as key regulators of mammary gland development in rodents and linked to human disease.

N-methyl-d-aspartate receptor hypofunction causes recurrent and transient failures of perceptual inference.

Perception integrates external sensory signals with internal predictions that reflect prior knowledge about the world. Previous research suggests that this integration is governed by slow alternations between an external mode, driven by sensory signals, and an internal mode, shaped by prior knowledge. Using a double-blind, placebo-controlled, cross-over experiment in healthy human participants, we investigated the effects of the N-Methyl-D-aspartate receptor (NMDAR) antagonist S-ketamine on the balance between external and internal modes.