A diazirine's central carbon is sp-hybridized, facilitating conjugation to dye molecules.

Diazirines are versatile carbene precursors that are extensively used in biological target identification experiments. However, their photo-activation wavelength ( 365 nm) precludes their use in living organisms. Here we show that a reconceptualization of the diazirine hybridization state leads to conjugation of the diazirine motif to longer-wavelength chromophores.

Development and validation of an interpretable machine learning-based calculator for predicting 5-year weight trajectories after bariatric surgery: a multinational retrospective cohort SOPHIA study.

Background: Weight loss trajectories after bariatric surgery vary widely between individuals, and predicting weight loss before the operation remains challenging. We aimed to develop a model using machine learning to provide individual preoperative prediction of 5-year weight loss trajectories after surgery.

Methods: In this multinational retrospective observational study we enrolled adult participants (aged ≥18 years) from ten prospective cohorts (including ABOS [NCT01129297], BAREVAL [NCT02310178], the Swedish Obese Subjects study, and a large cohort from the Dutch Obesity Clinic [Nederlandse Obesitas Kliniek]) and two randomised trials (SleevePass [NCT00793143] and SM-BOSS [NCT00356213]) in Europe, the Americas, and Asia, with a 5 year follow-up after Roux-en-Y gastric bypass, sleeve gastrectomy, or gastric band.

The Atypical Chemerin Receptor GPR1 Displays Different Modes of Interaction with β-Arrestins in Humans and Mice with Important Consequences on Subcellular Localization and Trafficking.

Atypical chemokine receptors (ACKRs) have emerged as a subfamily of chemokine receptors regulating the local bioavailability of their ligands through scavenging, concentration, or transport. The biological roles of ACKRs in human physiology and diseases are often studied by using transgenic mouse models. However, it is unknown whether mouse and human ACKRs share the same properties.

Construction of an automatic score for the evaluation of speech disorders among patients treated for a cancer of the oral cavity or the oropharynx: The Carcinologic Speech Severity Index.

Background: Speech disorders impact quality of life for patients treated with oral cavity and oropharynx cancers. However, there is a lack of uniform and applicable methods for measuring the impact on speech production after treatment in this tumor location.

Objective: The objective of this work is to (1) model an automatic severity index of speech applicable in clinical practice, that is equivalent or superior to a severity score obtained by human listeners, via several acoustics parameters extracted (a) directly from speech signal and (b) resulting from speech processing and (2) derive an automatic speech intelligibility classification (i.

Gemcitabine plus nab-paclitaxel until progression or alternating with FOLFIRI.3, as first-line treatment for patients with metastatic pancreatic adenocarcinoma: The Federation Francophone de Cancérologie Digestive-PRODIGE 37 randomised phase II study (FIRGEMAX).

Background: Chemotherapy is effective in metastatic pancreatic adenocarcinoma (mPA), but new approaches are still needed to improve patients' survival and quality of life. We have previously published good efficacy and tolerability results on a sequential treatment strategy of gemcitabine followed by an intensified FOLFIRI (5FU+irinotecan) regimen. In the present study, we evaluated the same sequence but replaced gemcitabine by the new gemcitabine + nab-paclitaxel standard first-line combination.

Growth references for weight, height, and body mass index for Ecuadorian children and adolescents aged 5-19 years.

Introduction: The assessment of growth during childhood and adolescence is a critical component of health care at all levels, but it is also part of nutritional status diagnosis and the timely detection of related conditions. Ecuador lacks national growth references, so it has decided to adopt the international standards proposed by the World Health Organization. The objective of this study was to develop national references for weight, height, and body mass index for children and adolescents.

Rewards interact with repetition-dependent learning to enhance long-term retention of motor memories.

The combination of behavioral experiences that enhance long-term retention remains largely unknown. Informed by neurophysiological lines of work, this study tested the hypothesis that performance-contingent monetary rewards potentiate repetition-dependent forms of learning, as induced by extensive practice at asymptote, to enhance long-term retention of motor memories. To this end, six groups of 14 participants (n = 84) acquired novel motor behaviors by adapting to a gradual visuomotor rotation while these factors were manipulated.

Further refinement of COL4A1 and COL4A2 related cortical malformations.

Unlabelled: Mutations in COL4A1 have been reported in schizencephaly and porencephaly combined with microbleeds or calcifications, often associated with ocular and renal abnormalities, myopathy, elevated creatine kinase levels and haemolytic anaemia. In this study, we aimed to clarify the phenotypic spectrum of COL4A1/A2 mutations in the context of cortical malformations that include schizencephaly, polymicrogyria and/or heterotopia.

Methods: We screened for COL4A1/A2 mutations in 9 patients with schizencephaly and/or polymicrogyria suspected to be caused by vascular disruption and leading to a cerebral haemorrhagic ischaemic event.

Strong-Isospin-Breaking Correction to the Muon Anomalous Magnetic Moment from Lattice QCD at the Physical Point.

All lattice-QCD calculations of the hadronic-vacuum-polarization contribution to the muon's anomalous magnetic moment to date have been performed with degenerate up- and down-quark masses. Here we calculate directly the strong-isospin-breaking correction to a_{μ}^{HVP} for the first time with physical values of m_{u} and m_{d} and dynamical u, d, s, and c quarks, thereby removing this important source of systematic uncertainty. We obtain a relative shift to be applied to lattice-QCD results obtained with degenerate light-quark masses of δa_{μ}^{HVP,m_{u}≠m_{d}}=+1.

Structural Basis of Outstanding Multivalent Effects in Jack Bean α-Mannosidase Inhibition.

Multivalent design of glycosidase inhibitors is a promising strategy for the treatment of diseases involving enzymatic hydrolysis of glycosidic bonds in carbohydrates. An essential prerequisite for successful applications is the atomic-level understanding of how outstanding binding enhancement occurs with multivalent inhibitors. Herein we report the first high-resolution crystal structures of the Jack bean α-mannosidase (JBα-man) in apo and inhibited states.

Prospective validation of a lymphocyte infiltration prognostic test in stage III colon cancer patients treated with adjuvant FOLFOX.

Background: The prognostic value of lymphocyte infiltration (LI) of colorectal carcinoma (CC) has been demonstrated by several groups. However, no validated test is currently available for clinical practice. We previously described an automated and reproducible method for testing LI and aimed to validate it for clinical use.

The human gut microbiome and its dysfunctions through the meta-omics prism.

The microorganisms inhabiting the human gut are abundant (10(14) cells) and diverse (approximately 500 species per individual). It is now acknowledged that the microbiota has coevolved with its host to achieve a symbiotic relationship, leading to physiological homeostasis. The gut microbiota ensures vital functions, such as food digestibility, maturation of the host immune system, and protection against pathogens.

A Phylogenetically Conserved Group of Nuclear Factor-Y Transcription Factors Interact to Control Nodulation in Legumes.

The endosymbiotic association between legumes and soil bacteria called rhizobia leads to the formation of a new root-derived organ called the nodule in which differentiated bacteria convert atmospheric nitrogen into a form that can be assimilated by the host plant. Successful root infection by rhizobia and nodule organogenesis require the activation of symbiotic genes that are controlled by a set of transcription factors (TFs). We recently identified Medicago truncatula nuclear factor-YA1 (MtNF-YA1) and MtNF-YA2 as two M.

Short-range inversions: rethinking organelle genome stability: template switching events during DNA replication destabilize organelle genomes.

In the organelles of plants and mammals, recent evidence suggests that genomic instability stems in large part from template switching events taking place during DNA replication. Although more than one mechanism may be responsible for this, some similarities exist between the different proposed models. These can be separated into two main categories, depending on whether they involve a single-strand-switching or a reciprocal-strand-switching event.

Two CCAAT-box-binding transcription factors redundantly regulate early steps of the legume-rhizobia endosymbiosis.

During endosymbiotic interactions between legume plants and nitrogen-fixing rhizobia, successful root infection by bacteria and nodule organogenesis requires the perception and transduction of bacterial lipo-chitooligosaccharidic signal called Nod factor (NF). NF perception in legume roots leads to the activation of an early signaling pathway and of a set of symbiotic genes which is controlled by specific early transcription factors (TFs) including CYCLOPS/IPD3, NSP1, NSP2, ERN1 and NIN. In this study, we bring convincing evidence that the Medicago truncatula CCAAT-box-binding NF-YA1 TF, previously associated with later stages of rhizobial infection and nodule meristem formation is, together with its closest homolog NF-YA2, also an essential positive regulator of the NF-signaling pathway.

Brain morphology in children with 47, XYY syndrome: a voxel- and surface-based morphometric study.

The neurocognitive and behavioral profile of individuals with 47,XYY is increasingly documented; however, very little is known about the effect of a supernumerary Y-chromosome on brain development. Establishing the neural phenotype associated with 47,XYY may prove valuable in clarifying the role of Y-chromosome gene dosage effects, a potential factor in several neuropsychiatric disorders that show a prevalence bias toward males, including autism spectrum disorders. Here, we investigated brain structure in 10 young boys with 47,XYY and 10 age-matched healthy controls by combining voxel-based morphometry (VBM) and surface-based morphometry (SBM).

Childhood adversity as a risk for cancer: findings from the 1958 British birth cohort study.

Background: To analyse whether Adverse Childhood Experiences (ACE) are associated with an increased risk of cancer.

Methods: The National child development study (NCDS) is a prospective birth cohort study with data collected over 50 years. The NCDS included all live births during one week in 1958 (n=18558) in Great Britain.

Estimating controlled direct effects in the presence of intermediate confounding of the mediator-outcome relationship: Comparison of five different methods.

In mediation analysis between an exposure X and an outcome Y, estimation of the direct effect of X on Y by usual regression after adjustment for the mediator M may be biased if Z is a confounder between M and Y, and is also affected by X Alternative methods have been described to avoid such a bias: inverse probability of treatment weighting with and without weight truncation, the sequential g-estimator and g-computation. Our aim was to compare the usual linear regression adjusted for M to these methods when estimating the controlled direct effect between X and Y in the causal structure and to explore the size of the potential bias. Estimations were computed in several simulated data sets as well as real data.

[Application of detecting and taking overdispersion into account in Poisson regression model].

Background: Researchers often use the Poisson regression model to analyze count data. Overdispersion can occur when a Poisson regression model is used, resulting in an underestimation of variance of the regression model parameters. Our objective was to take overdispersion into account and assess its impact with an illustration based on the data of a study investigating the relationship between use of the Internet to seek health information and number of primary care consultations.

Refractory bleeding from gastroduodenal ulcers: arterial embolization in high-operative-risk patients.

Goals And Background: We evaluated the efficacy and medium-term outcomes of transcatheter embolization to control massive bleeding from gastroduodenal ulcers after failed endoscopic treatment in high-operative-risk patients.

Study: Retrospective study of 35 consecutive emergency embolization procedures in hemodynamically unstable patients (24 men, 11 women, mean age 71+/-11.6 y) referred from 1999 to 2006 for selective angiography after failed endoscopic treatment.