Genetically proxied impaired GIPR signaling and risk of 6 cancers.

Preclinical and genetic studies suggest that impaired glucose-dependent insulinotropic polypeptide receptor (GIPR) signaling worsens glycemic control. The relationship between GIPR signaling and the risk of cancers influenced by impaired glucose homeostasis is unclear. We examined the association of a variant in , rs1800437 (E354Q), shown to impair long-term GIPR signaling and lower circulating glucose-dependent insulinotropic peptide concentrations, with risk of 6 cancers influenced by impaired glucose homeostasis (breast, colorectal, endometrial, lung, pancreatic, and renal) in up to 235,698 cases and 333,932 controls.

Fully Automated Flow Protocol for C(sp)-C(sp) Bond Formation from Tertiary Amides and Alkyl Halides.

Herein, we present a novel C(sp)-C(sp) bond-forming protocol via the reductive coupling of abundant tertiary amides with organozinc reagents prepared from their corresponding alkyl halides. Using a multistep fully automated flow protocol, this reaction could be used for both library synthesis and target molecule synthesis on the gram-scale starting from bench-stable reagents. Additionally, excellent chemoselectivity and functional group tolerance make it ideal for late-stage diversification of druglike molecules.

Cardiorespiratory Monitoring Data to Predict Respiratory Outcomes in Extremely Preterm Infants.

Immature control of breathing is associated with apnea, periodic breathing, intermittent hypoxemia, and bradycardia in extremely preterm infants. However, it is not clear if such events independently predict worse respiratory outcome. To determine if analysis of cardiorespiratory monitoring data can predict unfavorable respiratory outcomes at 40 weeks postmenstrual age (PMA) and other outcomes, such as bronchopulmonary dysplasia at 36 weeks PMA.

Recognizing Ethyl Chloride Neurotoxicity: Inhalant Abuse Hidden in Plain Sight.

Ethyl chloride is a common topical anesthetic. However, when abused as an inhalant, effects can range from headaches and dizziness to debilitating neurotoxicity requiring intubation. While previous case reports describe the short-term reversible neurotoxicity of ethyl chloride, ours show chronic morbidity and mortality outcome.

Symptoms of dry eye related to the relative humidity of living places.

Purpose: To investigate the impact of relative humidity (RH) and climate variables of the place of residence on symptoms of dry eye disease (DED) in primary eye care practice.

Methods: A cross-sectional analysis of the Ocular Surface Disease Index (OSDI) dry eye classification of 1.033 patients [classified as non-DED (OSDI ≤22) and DED (OSDI >22)] was conducted in a multicentre study in Spain.

Association between circulating inflammatory markers and adult cancer risk: a Mendelian randomization analysis.

Background: Tumour-promoting inflammation is a "hallmark" of cancer and conventional epidemiological studies have reported links between various inflammatory markers and cancer risk. The causal nature of these relationships and, thus, the suitability of these markers as intervention targets for cancer prevention is unclear.

Methods: We meta-analysed 6 genome-wide association studies of circulating inflammatory markers comprising 59,969 participants of European ancestry.

Microbial peptides activate tumour-infiltrating lymphocytes in glioblastoma.

Microbial organisms have key roles in numerous physiological processes in the human body and have recently been shown to modify the response to immune checkpoint inhibitors. Here we aim to address the role of microbial organisms and their potential role in immune reactivity against glioblastoma. We demonstrate that HLA molecules of both glioblastoma tissues and tumour cell lines present bacteria-specific peptides.

Comparison of the PROMIS and iHOT-12 in Determining Satisfaction Levels After Hip Arthroscopy for FAIS.

Background: The Patient-Reported Outcomes Measurement Information System (PROMIS) has not been fully evaluated for outcomes assessment after hip arthroscopy to correct femoroacetabular impingement syndrome (FAIS).

Purpose/hypothesis: The purpose of this study was to compare the accuracy of the PROMIS Physical Function (PF) and Pain Interference (PI) subscales with the 12-Item International Hip Outcome Tool (iHOT-12) to define patients with 3 unique substantial clinical benefit (SCB) scores-patients who reported ≥80%, ≥90%, and 100% satisfaction at 1 year after hip arthroscopy for FAIS. We hypothesized that the iHOT-12 would be more accurate than the PROMIS-PF and PROMIS-PI subscales in identifying these 3 patient groups.

Cross-reactive EBNA1 immunity targets alpha-crystallin B and is associated with multiple sclerosis.

Multiple sclerosis (MS) is an inflammatory disease of the central nervous system, for which and Epstein-Barr virus (EBV) infection is a likely prerequisite. Due to the homology between Epstein-Barr nuclear antigen 1 (EBNA1) and alpha-crystallin B (CRYAB), we examined antibody reactivity to EBNA1 and CRYAB peptide libraries in 713 persons with MS (pwMS) and 722 matched controls (Con). Antibody response to CRYAB amino acids 7 to 16 was associated with MS (OR = 2.

Cu-Catalyzed C(sp) Amination of Unactivated Secondary Alkyl Iodides Promoted by Diaryliodonium Salts.

Herein, we describe the development of a copper-catalyzed C(sp) amination of unactivated secondary alkyl iodides mediated by diaryliodonium salts. Our protocol is enabled by the intermediacy of aryl radical species that undergo halogen atom transfer prior to interfacing with copper catalysts, thus setting the basis for a C-N bond formation at sp-hybridized carbons. The method is characterized by its mild reaction conditions, excellent regioselectivity, and wide substrate scope.

ODNA: identification of organellar DNA by machine learning.

Motivation: Identifying organellar DNA, such as mitochondrial or plastid sequences, inside a whole genome assembly, remains challenging and requires biological background knowledge. To address this, we developed ODNA based on genome annotation and machine learning to fulfill.

Results: ODNA is a software that classifies organellar DNA sequences within a genome assembly by machine learning based on a predefined genome annotation workflow.

Addressing uncertainties in correlative imaging of exogenous particles with the tissue microanatomy with synchronous imaging strategies.

Exposure to exogenous particles is of increasing concern to human health. Characterizing the concentrations, chemical species, distribution, and involvement of the stimulus with the tissue microanatomy is essential in understanding the associated biological response. However, no single imaging technique can interrogate all these features at once, which confounds and limits correlative analyses.

Hypoxemia events in preterm neonates are associated with urine oxidative biomarkers.

Background: Intermittent hypoxemia (IH) events are common in preterm neonates and are associated with adverse outcomes. Animal IH models can induce oxidative stress. We hypothesized that an association exists between IH and elevated peroxidation products in preterm neonates.

Plasma serotonergic biomarkers are associated with hypoxemia events in preterm neonates.

Background: Hypoxemia is a physiological manifestation of immature respiratory control in preterm neonates, which is likely impacted by neurotransmitter imbalances. We investigated relationships between plasma levels of the neurotransmitter serotonin (5-HT), metabolites of tryptophan (TRP), and parameters of hypoxemia in preterm neonates.

Methods: TRP, 5-HT, 5-hydroxyindoleacetic acid (5-HIAA), and kynurenic acid (KA) were analyzed in platelet-poor plasma at ~1 week and ~1 month of life from a prospective cohort of 168 preterm neonates <31 weeks gestational age (GA).

Reduction of neutrophil extracellular traps accelerates inflammatory resolution and increases bone formation on titanium implants.

Neutrophils are the most abundant immune cells in the blood and the first cells to be recruited to the biomaterial implantation site. Neutrophils are fundamental in recruiting mononuclear leukocytes to mount an immune response at the injury site. Neutrophils exert significant pro-inflammatory effects through the release of cytokines and chemokines, degranulation and release of myeloperoxidase (MPO) and neutrophil elastase (NE), and the production of large DNA-based networks called neutrophil extracellular traps (NETs).

Neutrophil elastase decreases SARS-CoV-2 spike protein binding to human bronchial epithelia by clipping ACE-2 ectodomain from the epithelial surface.

Patients with cystic fibrosis (CF) have decreased severity of severe acute respiratory syndrome-like coronavirus-2 (SARS-CoV-2) infections, but the underlying cause is unknown. Patients with CF have high levels of neutrophil elastase (NE) in the airway. We examined whether respiratory epithelial angiotensin-converting enzyme 2 (ACE-2), the receptor for the SARS-CoV-2 spike protein, is a proteolytic target of NE.

A theoretical and experimental investigation on a volume coil with slotted end-rings for rat MRI at 7 T.

Objective: A volume coil with squared slots-end ring was developed to attain improved sensitivity for imaging of rat's brain at 7 T.

Material And Methods: The principles of the high cavity resonator for the low-pass case and the law of Biot-Savart were used to derive a theoretical expression of [Formula: see text]. The slotted-end ring resonator showed a theoretical 2.

Seven-colour multiplex immunochemistry/immunofluorescence and whole slide imaging of frozen sections.

Multiplex Immunochemistry/Immunofluorescence (mIHC/IF) aims to visualise multiple biomarkers in a single tissue section and is especially powerful when used on slide scanners coupled with digital analysis tools. mIHC/IF is commonly employed in immuno-oncology to characterise features of the tumour microenvironment (TME) and correlate them with clinical parameters to guide prognostication and therapy. However, mIHC/IF can be applied to a wide range of organisms in any physiological or disease context.

Foliar functional and genetic variation in a keystone Hawaiian tree species estimated through spectroscopy.

Imaging spectroscopy has the potential to map closely related plant taxa at landscape scales. Although spectral investigations at the leaf and canopy levels have revealed relationships between phylogeny and reflectance, understanding how spectra differ across, and are inherited from, genotypes of a single species has received less attention. We used a common-garden population of four varieties of the keystone canopy tree, Metrosideros polymorpha, from Hawaii Island and four F1-hybrid genotypes derived from controlled crosses to determine if reflectance spectra discriminate sympatric, conspecific varieties of this species and their hybrids.

Genetically proxied glucose-lowering drug target perturbation and risk of cancer: a Mendelian randomisation analysis.

Aims/hypothesis: Epidemiological studies have generated conflicting findings on the relationship between glucose-lowering medication use and cancer risk. Naturally occurring variation in genes encoding glucose-lowering drug targets can be used to investigate the effect of their pharmacological perturbation on cancer risk.

Methods: We developed genetic instruments for three glucose-lowering drug targets (peroxisome proliferator activated receptor γ [PPARG]; sulfonylurea receptor 1 [ATP binding cassette subfamily C member 8 (ABCC8)]; glucagon-like peptide 1 receptor [GLP1R]) using summary genetic association data from a genome-wide association study of type 2 diabetes in 148,726 cases and 965,732 controls in the Million Veteran Program.

Structural and functional analysis of the cerato-platanin-like protein Cpl1 suggests diverging functions in smut fungi.

Plant-pathogenic fungi are causative agents of the majority of plant diseases and can lead to severe crop loss in infected populations. Fungal colonization is achieved by combining different strategies, such as avoiding and counteracting the plant immune system and manipulating the host metabolome. Of major importance are virulence factors secreted by fungi, which fulfil diverse functions to support the infection process.

Effects of dietary extrusion on rumen fermentation, nutrient digestibility, performance and milk composition of dairy cattle: a meta-analysis.

Objective: The present study aimed to evaluate the effects of extruded and unextruded feeding on the performance, milk composition, digestibility and ruminal fermentation of dairy cows through a meta-analysis.

Methods: The database was compiled from 53 studies in Scopus and PubMed. The data were analyzed using a random effects model in OpenMEE software.

Addressing Gendered Racism Against Black Girls Using a Strengths-Based Empowerment-Intersectional Framework for Sexual Health and Substance Use Prevention Programming.

Although Black girls use substances at lower rates than boys and girls from various other racial groups, they tend to have worse health outcomes associated with substance use that can also impact their sexual health. The association between substance use and sexual risk behaviors is usually attributed to lack of access to quality health care and lack of culturally specific prevention programming and treatment options tailored to this group. Accordingly, the theoretical frameworks for health promotion for Black girls often focus on addressing deficits, ignoring the powerful and intersecting social forces that can impact identity, agency, and behavioral options.