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Online meetings have become increasingly prevalent, especially during the coronavirus disease 2019 pandemic. Although they offer convenience and effectiveness in various contexts, there is a pertinent question about whether they truly replicate the richness of in-person communication. This study delves into the distinctions between online and face-to-face interactions, with a particular focus on the synchronization of brain activity. Previous research has indicated a connection between synchronization and the quality of communication. Therefore, our hypothesis posits that face-to-face interactions lead to greater brain synchronization compared to online interactions, which often lack certain social cues. To investigate this, we conducted a study using functional near-infrared spectroscopy hyperscanning during an eye-contact task involving 28 male participants organized into 14 pairs. We assessed brain signal synchronization using wavelet coherence analysis. After comparing face-to-face and online conditions, our findings revealed significantly higher synchronization in face-to-face scenarios, particularly within the right temporoparietal region. These results align with the outcomes of other hyperscanning studies and suggest that face-to-face communication elicits a higher level of brain synchronization compared with online communication. In the future, this approach holds promise for evaluating the effectiveness of online meeting tools in achieving a more authentic virtual communication experience.

How do large-bodied frugivores contribute to seed dispersal of large-diaspore plants? This study examined seed dispersal effectiveness for two large-diaspore tree species, Astrotrichilia asterotricha ( AA ) and Abrahamia deflexa ( AD ), in a Madagascan forest. I evaluated fruit removal rates through focal tree observations and factors affecting seedling recruitment up to the 2-year-old seedling stage. I confirmed brown lemur ( Eulemur fulvus ) as the sole disperser, removing 58.8% and 26.0% of fruits produced by AA and AD . Brown lemurs frequently visited large-crowned AA trees with high density of fallen fruits and more adjacent fruiting trees during seasons with low fruit diversity. Most AA seedlings were removed by predators, although canopy openness slightly improved seedling establishment. Although AD seeds were severely attacked by predators under mother trees, the seedlings survived under dispersal conditions distant from the mother trees, and with low density of diaspores. AD had a higher cumulative probability from fruit removal to seedling recruitment (6.5%) than AA (1.5%) in the first rainy season. This study clarifies the significance of seed dispersal to tree recruitment strategies, which vary among different combinations of tree species and large frugivores, i.e. quantitative dispersal to reach suitable microhabitats, and qualitative dispersal to escape from dangerous zones near mother trees.

Nivolumab, an immune checkpoint inhibitor, is beneficial to patients with platinum-refractory recurrent or metastatic head and neck squamous cell carcinoma (R/M-HNSCC). However, platinum-sensitive R/M-HNSCC has not yet been studied. Hence, in this prospective study, we evaluated the efficacy and safety of nivolumab in patients with platinum-sensitive R/M-HNSCC. This prospective single-arm study was conducted in a single institution in Japan. Patients with platinum-sensitive R/M-HNSCC (defined as head and neck cancer that recurred or metastasized at least 6 months after platinum-based chemotherapy or chemoradiotherapy) were enrolled. The primary endpoint was overall survival (OS). The secondary endpoints were progression-free survival (PFS), overall response rate (ORR), immune-related adverse events (irAEs), and quality of life (QOL). This study was registered at the University Hospital Medical Information Network Clinical Trials Registry (UMIN000031324). Twenty-two patients with platinum-sensitive R/M-HNSCC were enrolled. The median OS was 17.4 months, and the 1-year OS rate was 73%. The median PFS was 9.6 months, 1-year PFS rate was 48%, and ORR was 36%. Sixteen irAEs were recorded in 12 patients; however, no grade 4 or 5 irAEs were observed. The QOL assessments revealed that nivolumab did not decrease the QOL of patients. Nivolumab is effective against platinum-sensitive R/M-HNSCC with acceptable safety.

BackgroundPeroral endoscopic myotomy (POEM) is a novel, minimally invasive treatment for esophageal achalasia. We retrospectively examined and evaluated the results following POEM to verify the technique’s efficacy and safety.MethodsWe retrospectively analyzed data for patients who underwent POEM at eight Japanese facilities between September 2008 and October 2015. Pre- and postoperative assessments 3 months and 1 year after POEM included patient interviews, endoscopy, and manometry.ResultsA total of 1346 patients underwent POEM during the study period. Achalasia was the straight type in 1105 patients (82%) and the sigmoid type in 241 patients (18%). The average patient age was 47.2 years (range 3–95 years); 617 patients (46%) were men and 729 (54%) were women. Previous treatment included balloon dilatation in 381 patients (28%) and Heller–Dor operation in 43 patients (3%). The average operation time was 99.6 min. The mean length of the myotomy in the esophageal body was 10.8 cm, and the myotomy extended into the stomach a mean of 2.8 cm. The response rate (Eckardt score ≤ 3) was 95.1% 3 months postoperatively and 94.7% 1 year postoperatively. We noted 50 adverse events (3.7%) of Clavien–Dindo classification grade ≤ IIIa, and all resolved with conservative treatment. There were no Clavien–Dindo classification grade ≥ IIIb adverse events. After POEM, erosive esophagitis according to the Los Angeles classification was absent in 37% of the patients, grade A in 33%, B in 24%, C in 6%, and D in 0.2%. Symptomatic gastroesophageal reflux disease after POEM was confirmed in 14.8% of the patients; both erosive esophagitis and symptomatic gastroesophageal reflux disease responded to treatment with a proton-pump inhibitor.ConclusionOur results confirmed the safety and efficacy of POEM in a large patient series and support POEM as the first-line and standard treatment for esophageal achalasia.

Activation of hepatocyte growth factor (HGF) by proteolytic processing is triggered in cancer microenvironments, and subsequent signaling through the MET receptor is involved in cancer progression. However, the structure of HGF remains elusive, and few small/medium-sized molecules can modulate HGF. Here, we identified HiP-8, a macrocyclic peptide consisting of 12 amino acids, which selectively recognizes active HGF. Biochemical analysis and real-time single-molecule imaging by high-speed atomic force microscopy demonstrated that HiP-8 restricted the dynamic domains of HGF into static closed conformations, resulting in allosteric inhibition. Positron emission tomography using HiP-8 as a radiotracer enabled noninvasive visualization and simultaneous inhibition of HGF–MET activation status in tumors in a mouse model. Our results illustrate the conformational change in proteolytic activation of HGF and its detection and inhibition by a macrocyclic peptide, which may be useful for diagnosis and treatment of cancers. A potent inhibitor for hepatocyte growth factor was identified that utilizes an allosteric mode of inhibition revealed by atomic force microscopy imaging. The inhibitor could be used for positron emission tomography imaging of mouse tumors.

BackgroundAchalasia has been reported to be associated with esophageal cancers (ECs). However, owing to the rarity of achalasia, details of achalasia-related ECs are not well investigated.MethodThe incidence of ECs in Japanese patients with achalasia and achalasia-related esophageal motility disorders (EMDs) was estimated, and risk factors for achalasia-related ECs were determined. Characteristics of ECs and treatment courses were also analyzed.ResultsBetween 2010 and 2019, 2714 Japanese patients with achalasia and achalasia-related EMDs were recorded in 7 high-volume centers; 24 patients (21 men, 3 women) developed ECs. The incidence of ECs was estimated at 0.078 and 0.28 per 100 person-years from the onset and the diagnosis of disease, respectively. Kaplan–Meier estimate suggested that, in addition to a long history of achalasia, advanced age, male sex, and regular alcohol consumption were statistically significant risk factors for EC development. A prevalence of 40 ECs (12.5% multiple lesions, and 22.7% metachronal lesions) was also noted, predominantly distributed over the thoracic esophagus. All were histologically diagnosed as squamous cell carcinoma. Superficial ECs were successfully treated with endoscopic treatment in all cases, except one. Achalasia-related Barret esophagus was extremely rare, and Barret adenocarcinoma was not detected in our cohort.ConclusionThe high relative risk of ECs was clarified in Japanese achalasia patients, although the absolute risk remained low. Therefore, surveillance endoscopy may be recommended in limited patients with several aforementioned risk factors determined. Superficial cancer can be treated with endoscopic treatment. Multiple and metachronal ECs should be screened.

Social media platforms offer unprecedented opportunities to study cultural evolution by analyzing digital traces. This study presents a methodological framework for analyzing the temporal dynamics of cultural modules in hashtag co-occurrence networks. We address the inherent challenges of analyzing dense, skewed, and highly variable cultural networks by introducing a perturbation ensemble clustering approach that distinguishes stable from unstable structural elements. By applying the Leiden algorithm to a perturbed ensemble of hashtag networks, we identify robust core modules and their stable periphery, and distinguish them from floating elements with unstable associations. Analysis of four years of data from a major photo-sharing platform reveals complex patterns in the evolution of cultural modules, including both stable associations and dynamic reorganizations. Our findings demonstrate how ensemble clustering techniques can effectively capture the interplay between stability and change in evolving cultural systems.

DNMT1 is an essential enzyme that maintains genomic DNA methylation, and its function is regulated by mechanisms that are not yet fully understood. Here, we report the cryo-EM structure of human DNMT1 bound to its two natural activators: hemimethylated DNA and ubiquitinated histone H3. We find that a hitherto unstudied linker, between the RFTS and CXXC domains, plays a key role for activation. It contains a conserved α-helix which engages a crucial “Toggle” pocket, displacing a previously described inhibitory linker, and allowing the DNA Recognition Helix to spring into the active conformation. This is accompanied by large-scale reorganization of the inhibitory RFTS and CXXC domains, allowing the enzyme to gain full activity. Our results therefore provide a mechanistic basis for the activation of DNMT1, with consequences for basic research and drug design. DNMT1 is an essential for maintaining genomic DNA methylation. Here, we report the cryo-EM structure of DNMT1 bound to ubiquitinated H3 and hemimethylated DNA, revealing structural insight into the activation mechanism of DNMT1.

Background Chronic low back pain (CLBP) is associated with significant disability and reductions in health related quality of life (HRQoL), which can negatively impact overall function and productivity. Depression is also associated with painful physical symptoms, and is often present in patients with chronic pain. However, the incremental burden associated with depression or symptoms of depression among CLBP patients is not well understood. The objective of this study was to investigate the impact of depression on HRQoL in CLBP and to assess the relationship between depression and work impairment and healthcare use among CLBP patients in Japan. Methods Data were extracted from the 2014 Japan National Health and Wellness Survey ( N  = 30,000). CLBP was defined by report of diagnosed low back pain ≥3 months duration. Depression was assessed using the Patient Health Questionnaire (PHQ-9). Measurements assessed included pain, HRQoL, labor force participation, work productivity and healthcare utilization. Patients with depression (PHQ-9 ≥ 10) were compared to patients without depression (PHQ-9 < 10) using t-tests for continuous and count variables and chi-square for categorical variables, which were followed by generalized linear models adjusted for covariates. The association between presenteeism and other patient outcomes and characteristics was analysed using nonparametric correlations (Spearman’s rho). Results Depressed CLBP patients had significantly more severe pain and higher levels of pain compared with patients without depression ( P  < 0.001). Depression was associated with worse HRQoL in CLBP patients. Presenteeism, overall work impairment and activity impairment were 1.8, 1.9 and 1.7 times as high, respectively, among those with depression relative to those without depression. CLBP patients with depression had almost twice as many healthcare provider visits in 6 months than those without depression. The pattern of results remained consistent after adjustment for sociodemographic and general health characteristics. Analysis also indicated presenteeism was closely related to overall work impairment (rho = 0.99). Conclusions Depression among CLBP patients in Japan was associated with higher pain scores and lower HRQoL scores, as well as lower labor productivity and increased healthcare use. Screening for depression in CLBP patients should be an essential part of CLBP patient care.

The Grignard reaction has a storied place in the development of organic chemistry. Recognized by the Nobel Prize more than a century ago, this coupling of organomagnesium halides with carbonyl compounds remains a widely used route to carbon-carbon bonds. Nguyen et al. review an emerging alternative protocol that replaces the sensitive magnesium reagent with a catalytically activated olefin and a reductant such as hydrogen or an alcohol. In addition to safety and efficiency considerations, this class of reactions benefits from the high abundance and low cost of the olefins. Science , this issue p. 300 Metal-catalyzed reductive coupling of olefin-derived nucleophiles: Reinventing carbonyl addition α-Olefins are the most abundant petrochemical feedstock beyond alkanes, yet their use in commodity chemical manufacture is largely focused on polymerization and hydroformylation. The development of byproduct-free catalytic C–C bond–forming reactions that convert olefins to value-added products remains an important objective. Here, we review catalytic intermolecular reductive couplings of unactivated and activated olefin-derived nucleophiles with carbonyl partners. These processes represent an alternative to the longstanding use of stoichiometric organometallic reagents in carbonyl addition.