Deoxygenative photochemical alkylation of secondary amides enables a streamlined synthesis of substituted amines.

Secondary amines are vital functional groups in pharmaceuticals, agrochemicals, and natural products, necessitating efficient synthetic methods. Traditional approaches, including N-monoalkylation and reductive amination, suffer from limitations such as poor chemoselectivity and complexity. Herein, we present a streamlined deoxygenative photochemical alkylation of secondary amides, enabling the efficient synthesis of α-branched secondary amines.

Genomics yields biological and phenotypic insights into bipolar disorder.

Bipolar disorder is a leading contributor to the global burden of disease. Despite high heritability (60-80%), the majority of the underlying genetic determinants remain unknown. We analysed data from participants of European, East Asian, African American and Latino ancestries (n = 158,036 cases with bipolar disorder, 2.

Applications of Artificial Intelligence in Dental Medicine: A Critical Review.

Introduction: Artificial intelligence (AI), including its subfields of machine learning and deep learning, is a branch of computer science and engineering focused on creating machines capable of tasks requiring human-like intelligence, such as visual perception, decision-making, and natural language processing. AI applications have become increasingly prevalent in dental medicine, generating high expectations as well as raising ethical and practical concerns.

Methods: This critical review evaluates the current applications of AI in dentistry, identifying key perspectives, challenges, and limitations in ongoing AI research.

Measuring the impact of hospitalisation for infectious diseases on the quality of life of older patients in four European countries: the AEQUI longitudinal matched cohort study (2020-2023).

Objectives: To evaluate the impact of hospitalisation for infectious diseases on the Health-Related Quality of life (HRQOL), multidimensional frailty, and functioning of older patients, we conducted a longitudinal matched cohort study in four European countries.

Methods: HRQOL, frailty, and functioning were assessed using validated questionnaires at inclusion, at discharge, and up to six months later (M6) in patients aged over 65 years hospitalised for severe acute respiratory or bloodstream infections, and matched controls hospitalised for non-infectious conditions. Comparative analyses employed multilevel mixed-effect linear or logistic models to assess changes from inclusion.

Phase I trial of ATR inhibitor elimusertib with FOLFIRI in advanced or metastatic gastrointestinal malignancies (ETCTN 10406).

Background: ATR is an apical DDR kinase activated at damaged replication forks. Elimusertib is an oral ATR inhibitor and potentiates irinotecan in human colorectal cancer models.

Methods: To establish dose and tolerability of elimusertib with FOLFIRI, a Bayesian Optimal Interval trial design was pursued.

What Are the Implications of Choosing a TAVR-First Strategy in the Lifetime Management of Aortic Stenosis?: A Critical Review of TAVR-Explant- and Redo-TAVR.

Some patients with aortic stenosis may require multiple valve interventions in their lifetime, and choosing transcatheter aortic valve replacement (TAVR) as the initial intervention may be appealing to many. If their transcatheter heart valve degenerates later in life, most will hope to undergo redo-TAVR. However, if redo-TAVR is not feasible, some may have to undergo surgical explantation of their transcatheter heart valve (TAVR-explant).

First Report of causing crown rot on (Olive) in Pakistan.

Crown rot impacted olive plants (cv. Koroneiki) in an orchard in Chakwal, Punjab, Pakistan (32° N, 72° E), with a prevalence of 60%. Observable symptoms included leaf chlorosis, defoliation, wilting, and twig dieback in 6-8-year-old plants, ultimately resulting in their demise (Fig.

Pembrolizumab and chemotherapy in high-risk, early-stage, ER/HER2 breast cancer: a randomized phase 3 trial.

Addition of pembrolizumab to neoadjuvant chemotherapy followed by adjuvant pembrolizumab improved outcomes in patients with high-risk, early-stage, triple-negative breast cancer. However, whether the addition of neoadjuvant pembrolizumab to chemotherapy would improve outcomes in high-risk, early-stage, estrogen receptor-positive/human epidermal growth factor receptor 2-negative (ER/HER2) breast cancer remains unclear. We conducted a double-blind, placebo-controlled phase 3 study (KEYNOTE-756) in which patients with previously untreated ER/HER2 grade 3 high-risk invasive breast cancer (T1c-2 (≥2 cm), cN1-2 or T3-4, cN0-2) were randomly assigned (1:1) to neoadjuvant pembrolizumab 200 mg or placebo Q3W given with paclitaxel QW for 12 weeks, followed by four cycles of doxorubicin or epirubicin plus cyclophosphamide Q2W or Q3W.

A hydrodynamic antenna: novel lateral line system in the tail of myliobatid stingrays.

Eagle rays, cownose rays and manta rays (order Myliobatiformes) have a slender tail that can be longer than the animal's body length, but its function and structure are unknown. Using histology, immunohistochemistry and three-dimensional imaging with micro-computed tomography scans, we describe the anatomy and function of the tail in , the cownose ray. The tail is an extension of the vertebral column with unique morphological specializations.

Personalized auricular vagus nerve stimulation: beat-to-beat deceleration dominates in systole-gated stimulation during inspiration - a pilot study.

Neuromodulation comes into focus as a non-pharmacological therapy with the vagus nerve as modulation target. The auricular vagus nerve stimulation (aVNS) has emerged to treat chronic diseases while re-establishing the sympathovagal balance and activating parasympathetic anti-inflammatory pathways. aVNS leads still to over and under-stimulation and is limited in therapeutic efficiency.

Coplanar Dimeric Acceptors with Bathochromic Absorption and Torsion-Free Backbones through Precise Fluorination Enabling Efficient Organic Photovoltaics with 18.63% Efficiency.

Giant dimeric acceptors (GDAs), a sub-type of acceptor materials for organic solar cells (OSCs), have garnered much attention due to the synergistic advantages of their monomeric and polymeric acceptors, forming a well-defined molecular structure with a giant molecular weight for high efficiency and stability. In this study, for the first time, two new GDAs, DYF-V and DY2F-V are designed and synthesized for OSC operation, by connecting one vinylene linker with the mono-/di-fluorinated end group on two Y-series monomers, respectively. After fluorination, both DYF-V and DY2F-V exhibit bathochromic absorption and denser packing modes due to the stronger intramolecular charge transfer effect and torsion-free backbones.

Machine learning-driven prediction of medical expenses in triple-vessel PCI patients using feature selection.

Revascularization therapies, such as percutaneous coronary intervention (PCI) and coronary artery bypass grafting (CABG), alleviate symptoms and treat myocardial ischemia. Patients with multivessel disease, particularly those undergoing 3-vessel PCI, are more susceptible to procedural complications, which can increase healthcare costs. Developing efficient strategies for resource allocation has become a paramount concern due to tightening healthcare budgets and the escalating costs of treating heart conditions.

Triple-attentions based salient object detector for strip steel surface defects.

Accurate detection of surface defects on strip steel is essential for ensuring strip steel product quality. Existing deep learning based detectors for strip steel surface defects typically strive to iteratively refine and integrate the coarse outputs of the backbone network, enhancing the models' ability to express defect characteristics. Attention mechanisms including spatial attention, channel attention and self-attention are among the most prevalent techniques for feature extraction and fusion.

Longitudinal associations of flare and damage accrual in patients with systemic lupus erythematosus.

Objective: To estimate the prevalence of organ damage (damage) and flare and to examine longitudinal associations between flares and subsequent damage accrual, in patients with systemic lupus erythematosus (SLE).

Methods: Patients enrolled in the Asia Pacific Lupus Collaboration cohort with ≥3 years of prospectively captured data were studied. Flares were assessed at routine visits, while damage ((Systemic Lupus International Collaborating Clinics/American College of Rheumatology) Damage Index) was assessed annually.

Deep anterior chamber depth may be a risk factor for axial length growth in children.

Objective: To investigate and evaluate the progression of myopia and associated factors of axial length (AL) growth among children in Chongqing.

Methods: This six-month prospective study was conducted on students in grades 1 to 8 at a school in Chongqing, China. All participants underwent a standard ophthalmologic examination including uncorrected visual acuity (UCVA), noncycloplegic refraction, AL, and corneal topography in March 2023.

Structural insights into human topoisomerase 3β DNA and RNA catalysis and nucleic acid gate dynamics.

Type IA topoisomerases (TopoIAs) are present in all living organisms. They resolve DNA/RNA catenanes, knots and supercoils by breaking and rejoining single-stranded DNA/RNA segments and allowing the passage of another nucleic acid segment through the break. Topoisomerase III-β (TOP3B), the only RNA topoisomerase in metazoans, promotes R-loop disassembly and translation of mRNAs.

Foliar application of 24-epibrassinolide enhances leaf nicotine content under low temperature conditions during the mature stage of flue-cured tobacco by regulating cold stress tolerance.

Background: Low temperatures disrupt nitrogen metabolism in tobacco, resulting in lower nicotine content in the leaves. 24-epibrassinolide (EBR) is a widely used plant growth regulator known for its roles in enhancing cold tolerance and nitrogen metabolism. Nevertheless, it remains unclear whether EBR enhances leaf nicotine content under low temperature conditions during the mature stage of flue-cured tobacco.

Supramolecular Interface Buffer Layer for Stable Zinc Anode.

The aqueous zinc ion batteries (AZIBs) are chronically plagued by the inevitable side-reaction and uneven Zn planets stack. Through regulating the water activity and Zn crystal dynamics could effectively relieve those anode/electrolyte interface problems. The (2-hydroxypropyl)-β-cyclodextrin (HBCD), characterized by the excluded-volume and mitigating zinc-flux aggregation effect, is chosen as the electrolyte additive to tail the anode/electrolyte interface.

Acceptor Elongation Boosted Intersystem Crossing Affords Efficient NIR Type-I and AIE-Active Photosensitizers for Targeting Ferroptosis-Based Cancer Therapy.

Photosensitizers (PSs) featuring type I reactive oxygen species (ROS) generation and aggregation-induced emission (AIE) activity offer a promising solution to achieve non-invasive and precise theranostics. However, the reported AIE luminogens (AIEgens) with both AIE characteristic and strong type-I ROS generation are still scarce and the structure-property relationship is still unclear. Herein, an innovative acceptor elongation boosted intersystem crossing (AEBIC) design strategy has been proposed to endow the AIEgen strong type-I ROS producibility.

The ANFIS-RSM based multi-objective optimization and modelling of ultrasound-assisted extraction of polyphenols from jamun fruit (Syzygium cumini).

Given their potential as natural substitutes for artificial additives and their health advantages, the extraction of bioactive substances like polyphenols from plant sources is becoming more and more significant. Nevertheless, it is still difficult to achieve effective extraction with minimal time and energy. In order to optimize polyphenol extraction from ripe jamun fruit pulp, including traditional and ultrasound-assisted methods, this study assessed the prediction power of response surface methodology (RSM) and adaptive neuro-fuzzy inference systems (ANFIS).

Impact of Varicocele on The Expression of Testicular Enzymes Involved in The Transsulfuration Pathway.

Background: Oxidative aggression is a hallmark of varicocele and may depend on decreased reactive ability of the endogenous antioxidant system following heat stress. We aimed to investigate the underlying mechanisms. Therefore, the expression of the main enzyme proteins involved in the generation of endogenous antioxidant power, cystathionine beta-synthase (CBS), cystathionine gamma-lyase (CSE), heme oxygenase (HO-1), and also, some of the metabolites (methionine, homocysteine, taurine and vitamin B6) reporting on their activity was investigated using a surgical varicocele model in rats.

The GeoTox Package: open-source software for connecting spatiotemporal exposure to individual and population-level risk.

Background: Comprehensive environmental risk characterization, encompassing physical, chemical, social, ecological, and lifestyle stressors, necessitates innovative approaches to handle the escalating complexity. This is especially true when considering individual and population-level diversity, where the myriad combinations of real-world exposures magnify the combinatoric challenges. The GeoTox framework offers a tractable solution by integrating geospatial exposure data from source-to-outcome in a series of modular, interconnected steps.

The Interplay between Metabolic Reprogramming, Mitochondrial Impairment, and Steroid Response in Proliferative Vitreoretinopathy.

Proliferative vitreoretinopathy (PVR) is a major cause of rhegmatogenous retinal detachment repair failure. Despite many attempts to find therapeutics for PVR, no pharmacotherapy has been proven effective. Steroids, as the epitome, show uncertain clinical effectiveness, which lacks an explanation and hints at unappreciated mechanisms of PVR.

FadA antigen of Fusobacterium nucleatum: implications for ceRNA network in colorectal cancer and adenomatous polyps progression.

Introduction: Colorectal cancer (CRC) is the second most common cause of cancer-related deaths globally. The gut microbiota, along with adenomatous polyps (AP), has emerged as a plausible contributor to CRC progression. This study aimed to scrutinize the impact of the FadA antigen derived from Fusobacterium nucleatum on the expression levels of the ANXA2 ceRNA network and assess its relevance to CRC advancement.