Could London Dispersion Force Control Regioselective (2 + 2) Cyclodimerizations of Benzynes? YES: Application to the Synthesis of Helical Biphenylenes.

In recent years, London dispersion interactions, which are the attractive component of the van der Waals potential, have been found to play an important role in controlling the regio- and/or stereoselectivity of various reactions. Particularly, the dispersion interactions between substrates and catalysts (or ligands) are dominant in various selective catalyzes. In contrast, repulsive steric interactions, rather than the attractive dispersion interactions, between bulky substituents are predominant in most of the noncatalytic reactions. Herein, we demonstrate the first example of London dispersion-controlled noncatalytic (2 + 2) cyclodimerization of substituted benzynes to selectively afford proximal biphenylenes in high yields and regioselectivities, depending on the extent of dispersion interactions in the substituents. This method can be applied for the synthesis of novel helical biphenylenes, which would be fascinating for chemists as these compounds are potential skeletons for ligands, catalysts, and medicines.

Optimal length of R-R interval segment window for Lorenz plot detection of paroxysmal atrial fibrillation by machine learning.

BACKGROUND: Heartbeat interval Lorenz plot (LP) imaging is a promising method for detecting atrial fibrillation (AF) in long-term monitoring, but the optimal segment window length for the LP images is unknown. We examined the performance of AF detection by LP images with different segment window lengths by machine learning with convolutional neural network (CNN). LP images with a 32 × 32-pixel resolution of non-overlapping segments with lengths between 10 and 500 beats were created from R-R intervals of 24-h ECG in 52 patients with chronic AF and 58 non-AF controls as training data and in 53 patients with paroxysmal AF and 52 non-AF controls as test data. For each segment window length, discriminant models were made by fivefold cross-validation subsets of the training data and its classification performance was examined with the test data. RESULTS: In machine learning with the training data, the averages of cross-validation scores were 0.995 and 0.999 for 10 and 20-beat LP images, respectively, and > 0.999 for 50 to 500-beat images. The classification of test data showed good performance for all segment window lengths with an accuracy from 0.970 to 0.988. Positive likelihood ratio for detecting AF segments, however, showed a convex parabolic curve linear relationship to log segment window length and peaked at 85 beats, while negative likelihood ratio showed monotonous increase with increasing segment window length. CONCLUSIONS: This study suggests that the optimal segment window length that maximizes the positive likelihood ratio for detecting paroxysmal AF with 32 × 32-pixel LP image is 85 beats.

Low Phase Angle Is Correlated With Worse General Condition in Patients with Advanced Cancer.

OBJECTIVES: Phase angle (PA) is a poor prognostic factor in patients with advanced cancer. This study aimed to identify possible correlations between PA and symptoms, quality of life, fluid retention, and laboratory data in cancer patients in palliative care settings. METHODS: Individuals who visited the outpatient clinic or were admitted to the palliative care unit were eligible. Patients with a performance status of 4 and/or those unable to complete questionnaires were excluded. PA was evaluated using a bioanalyzer device. The correlation coefficient between PA and the variables of interest was analyzed. RESULTS: A total of 102 patients were analyzed. PA was weakly correlated with age (ρ = -0.22), performance status (ρ = -0.30), functional well-being (ρ = 0.20), anorexia/cachexia subscale (ρ = 0.22), and Functional Assessment of Anorexia/Cachexia Therapy trial outcome index (ρ = 0.26). PA was also correlated with fluid retention (ρ = -0.34) and albumin (ρ = 0.32), C-reactive protein (ρ = -0.31), and hemoglobin (ρ = 0.41) levels. Sub-analysis stratified according to sex revealed that males demonstrated the same results; however, female sex demonstrated a correlation between PA and social well-being (ρ = -0.43). CONCLUSIONS: PA was correlated with physical condition, but not with psychological well-being.

The Saccharomyces cerevisiae AMPK, Snf1, Negatively Regulates the Hog1 MAPK Pathway in ER Stress Response.

Accumulation of unfolded proteins in the lumen of the endoplasmic reticulum (ER) causes ER stress. Snf1, the Saccharomyces cerevisiae ortholog of AMP-activated protein kinase (AMPK), plays a crucial role in the response to various environmental stresses. However, the role of Snf1 in ER stress response remains poorly understood. In this study, we characterize Snf1 as a negative regulator of Hog1 MAPK in ER stress response. The snf1 mutant cells showed the ER stress resistant phenotype. In contrast, Snf1-hyperactivated cells were sensitive to ER stress. Activated Hog1 levels were increased by snf1 mutation, although Snf1 hyperactivation interfered with Hog1 activation. Ssk1, a specific activator of MAPKKK functioning upstream of Hog1, was induced by ER stress, and its induction was inhibited in a manner dependent on Snf1 activity. Furthermore, we show that the SSK1 promoter is important not only for Snf1-modulated regulation of Ssk1 expression, but also for Ssk1 function in conferring ER stress tolerance. Our data suggest that Snf1 downregulates ER stress response signal mediated by Hog1 through negatively regulating expression of its specific activator Ssk1 at the transcriptional level. We also find that snf1 mutation upregulates the unfolded protein response (UPR) pathway, whereas Snf1 hyperactivation downregulates the UPR activity. Thus, Snf1 plays pleiotropic roles in ER stress response by negatively regulating the Hog1 MAPK pathway and the UPR pathway.

Ultrasonography for Eating and Swallowing Assessment: A Narrative Review of Integrated Insights for Noninvasive Clinical Practice.

Dysphagia is a syndrome of abnormal eating function resulting from a variety of causative diseases, and is associated with malnutrition. To date, the swallowing function has been difficult to examine without the use of invasive and expensive methods, such as the videofluorographic swallowing study or fiberoptic endoscopic evaluation of swallowing. In recent years, progress has been made in the clinical application of ultrasound equipment for the evaluation of body compositions near the body surface, including the assessment of nutritional status. Ultrasound examination is a noninvasive procedure and relatively inexpensive, and the equipment required is highly portable thanks to innovations such as wireless probes and tablet monitoring devices. The process of using ultrasound to visualize the geniohyoid muscle, digastric muscle, mylohyoid muscle, hyoid bone, tongue, masseter muscle, genioglossus muscle, orbicularis oris muscle, temporalis muscle, pharynx, esophagus, and larynx, and the methods used for evaluating these structures, are provided in this study in detail. This study also aims to propose a protocol for the assessment of swallowing-related muscles that can be applied in real-world clinical practice for the diagnosis of sarcopenic dysphagia, which can occur in elderly patients with sarcopenia, and has received much attention in recent years.