Sensory-motor systems can extract statistical regularities in dynamic uncertain environments, enabling quicker responses and anticipatory behavior for expected events. Anticipatory smooth pursuit eye movements (aSP) have been observed in primates when the temporal and kinematic properties of a forthcoming visual moving target are fully or partially predictable. To investigate the nature of the internal model of target kinematics underlying aSP, we tested the effect of varying the target kinematics and its predictability.
View Article and Find Full Text PDFIn amyotrophic lateral sclerosis (ALS), early mitochondrial dysfunction may contribute to progressive motor neuron loss. Remarkably, the ectopic expression of the Orthobornavirus bornaense type 1 (BoDV-1) X protein in mitochondria blocks apoptosis and protects neurons from degeneration. Therefore, this study examines the neuroprotective effects of X protein in an ALS mouse model.
View Article and Find Full Text PDFProvence rosé wines have gained global popularity, making them vulnerable to fraud. This study aimed to identify specific chemical markers to detect counterfeit Provence rosé wines. An untargeted LC-MS-based metabolomics analysis was performed on a set of 30 wines classified as "Provence," "Non-Provence," and "Provence imitations.
View Article and Find Full Text PDFPI3Kα, consisting of the p110α isoform of the catalytic subunit of PI 3-kinase (encoded by PIK3CA) and the p85α regulatory subunit (encoded by PI3KR1) is activated by growth factor receptors. The identification of common oncogenic mutations in PIK3CA has driven the development of many inhibitors that bind to the ATP-binding site in the p110α subunit. Upon activation, PI3Kα undergoes conformational changes that promote its membrane interaction and catalytic activity, yet the effects of ATP-site directed inhibitors on the PI3Kα membrane interaction are unknown.
View Article and Find Full Text PDFBackground: Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is an autoimmune disease of the peripheral nervous system that can lead to severe disability from muscle weakness and sensory disturbances. Around a third of patients do not respond to currently available treatments, and many patients with a partial response have residual neurological impairment, highlighting the need for effective alternatives. Efgartigimod alfa, a human IgG1 antibody Fc fragment, has demonstrated efficacy and safety in patients with generalised myasthenia gravis.
View Article and Find Full Text PDFBackground And Objective: The Yorkshire Kidney Screening Trial (YKST) assessed the feasibility of adding abdominal noncontrast computed tomography (NCCT) to lung cancer screening to screen for kidney cancer and other abdominal pathology.
Methods: A prospective diagnostic study offered abdominal NCCT to 55-80-yr-old ever-smokers attending a UK randomised lung cancer screening trial (May 2021 to October 2022). The exclusion criteria were dementia, frailty, previous kidney/lung cancer, and computed tomography (CT) of the abdomen and thorax within previous 6 and 12 mo, respectively.
Age at menopause (AOM) has a substantial impact on fertility and disease risk. While many loci with variants that associate with AOM have been identified through genome-wide association studies (GWAS) under an additive model, other genetic models are rarely considered. Here through GWAS meta-analysis under the recessive model of 174,329 postmenopausal women from Iceland, Denmark, the United Kingdom (UK; UK Biobank) and Norway, we study low-frequency variants with a large effect on AOM.
View Article and Find Full Text PDFBackground: Mycosis fungoides (MF) usually has an indolent course. However, some patients develop more aggressive disease and few prognostic parameters have been identified. Isolated cases of pustular MF (pMF) suggest an unfavourable prognosis.
View Article and Find Full Text PDFAutoimmune thyroid disease (AITD) is a common autoimmune disease. In a GWAS meta-analysis of 110,945 cases and 1,084,290 controls, 290 sequence variants at 225 loci are associated with AITD. Of these variants, 115 are previously unreported.
View Article and Find Full Text PDFObjectives: The Yorkshire Kidney Screening Trial (YKST) is a feasibility study of adding non-contrast abdominal CT scanning to screen for kidney cancer and other abdominal malignancies to community-based CT screening for lung cancer within the Yorkshire Lung Screening Trial (YLST). This study explored the acceptability of the combined screening approach to participants and healthcare professionals (HCPs) involved in the trial.
Methods: We conducted semi-structured interviews with eight HCPs and 25 participants returning for the second round of scanning within YLST, 20 who had taken up the offer of the additional abdominal CT scan and five who had declined.
Background: The initiation of early non-invasive ventilation (NIV) often involves a careful balance between tolerance and effectiveness. In amyotrophic lateral sclerosis (ALS) patients, the establishment of a strategy, including the decision to focus on adhering to a cut-off, setting specific targets, or correcting all events, is crucial.
Objective: To identify factors at 1 month after early at-home NIV initiation that are associated with improved survival in ALS patients.
Background: Performing large randomized trials in anesthesiology is often challenging and costly. The clinically integrated randomized trial is characterized by simplified logistics embedded into routine clinical practice, enabling ease and efficiency of recruitment, offering an opportunity for clinicians to conduct large, high-quality randomized trials under low cost. Our aims were to (1) demonstrate the feasibility of the clinically integrated trial design in a high-volume anesthesiology practice and (2) assess whether trial quality improvement interventions led to more balanced accrual among study arms and improved trial compliance over time.
View Article and Find Full Text PDFThe radical Truce-Smiles rearrangement is a straightforward strategy for incorporating aryl groups into organic molecules for which asymmetric processes remains rare. By employing a readily available and non-expensive chiral auxiliary, we developed a highly efficient asymmetric photocatalytic acyl and alkyl radical Truce-Smiles rearrangement of α-substituted acrylamides using tetrabutylammonium decatungstate (TBADT) as a hydrogen atom-transfer photocatalyst, along with aldehydes or C-H containing precursors. The rearranged products exhibited excellent diastereoselectivities (7 : 1 to >98 : 2 d.
View Article and Find Full Text PDFAn electrocatalytic synthesis of 2-pyrazolines dehydrogenative and defluorinative cross-coupling reactions between (hetero)arylaldehyde-derived ,-dialkylhydrazones and fluoromalonates is disclosed. Salient features of this work include (i) readily available starting materials, (ii) practical reaction conditions, and (ii) a formal oxidative (4 + 1)-cycloaddition triple C-H bond functionalization. Cyclic voltammetry analyses support the electrocatalytic formation of an α-fluoromalonyl radical.
View Article and Find Full Text PDFA cascade radical cyclization of alkenyl -cyanamides with aromatic aldehydes has been achieved for an expeditious synthesis of keto-methylated dihydropyrrolo-quinazolinones. Benzoyl radicals, generated from aryl aldehydes in the presence of di--butyl peroxide (DTBP), promoted the domino annulations leading to distinctive functionalized quinazolinones in good yields. In addition, the robustness of the present protocol is validated by employing heterocyclic and natural product-based aldehydes.
View Article and Find Full Text PDFAn electrochemical radical Truce Smiles rearrangement of N-allylbenzamides is documented herein. The selective 1,4-aryl migration was triggered by the radical fluoromethylation of the alkene providing a direct route to fluoro derivatives of the highly privileged β-arylethylamine pharmacophore. This practical transformation utilizes readily available starting materials and employs an electrical current to drive the oxidative process under mild reaction conditions.
View Article and Find Full Text PDFPurpose: In response to a nationwide fentanyl shortage, our institution assessed whether changing our first-line postoperative intravenous opioid from fentanyl to hydromorphone impacted patient outcomes. The primary research aim was to evaluate the association between first-line opioid and rapidity of recovery.
Design: The study team retrospectively obtained data on all consecutive patients extracted from the electronic medical record.
Xenotransplantation could be an inexhaustible source of organs and change the life of end-stage kidney disease patients with reduction of morbidity and mortality. Through genetic engineering it is now possible to reduce the risk of hyperacute and acute graft rejection and improve the overall immune compatibility between two different species. Some experiments have already brought promising perspectives.
View Article and Find Full Text PDF