Explore the vast range of titles available.

Forward head posture (FHP) is a serious problem causing head and neck disability, but the characteristics of muscle activity during long-term postural maintenance are unclear. This study aimed to investigate a comparison of electromyography (EMG) activation properties and subjective fatigue between young adults with and without habitual FHP. In this study, we examined the changes in the spatial and temporal distribution patterns of muscle activity using high-density surface EMG (HD-SEMG) in addition to mean frequency, a conventional measure of muscle fatigue. Nineteen male participants were included in the study (FHP group (n = 9; age = 22.3 ± 1.5 years) and normal group (n = 10; age = 22.5 ± 1.4 years)). Participants held three head positions (e.g., forward, backward, and neutral positions) for a total of 30 min each, and the EMG activity of the trapezius pars descendens muscle during posture maintenance was measured by HD-SEMG. The root mean square (RMS), the modified entropy, and the correlation coefficient were calculated. Additionally, the visual analogue scale (VAS) was evaluated to assess subjective fatigue. The RMS, VAS, modified entropy, and correlation coefficients were significantly higher in the FHP group than in the normal group ( p  < 0.001). With increasing postural maintenance time, the modified entropy and correlation coefficient values significantly decreased, and the mean frequency and VAS values significantly increased ( p  < 0.001). Furthermore, the forward position had significantly higher RMS, correlation coefficient, modified entropy, and VAS values than in the neutral position ( p  < 0.001). The HD-SEMG potential distribution patterns in the FHP group showed less heterogeneity and greater muscle activity in the entire muscle and subjective fatigue than those in the normal group. Excess muscle activity even in the neutral/comfortable position in the FHP group could potentially be a mechanism of neuromuscular conditions in this population.

Endovascular therapy for stroke is generally avoided if the cerebral infarction is large. In a trial conducted in Japan, the percentage of patients who had a good functional outcome at 90 days was higher with endovascular therapy than with medical care, but there were more cerebral hemorrhages with endovascular therapy.

Malaria infection elicits both protective and pathogenic immune responses, and IL‐27 is a critical cytokine that regulate effector responses during infection. Here, we identified a critical window of CD4 + T cell responses that is targeted by IL‐27. Neutralization of IL‐27 during acute infection with Plasmodium chabaudi expanded specific CD4 + T cells, which were maintained at high levels thereafter. In the chronic phase, Plasmodium‐ specific CD4 + T cells in IL‐27‐neutralized mice consisted mainly of CD127 + KLRG1 − and CD127 − KLRG1 + subpopulations that displayed distinct cytokine production, proliferative capacity, and are maintained in a manner independent of active infection. Single‐cell RNA‐seq analysis revealed that these CD4 + T cell subsets formed independent clusters that express unique Th1‐type genes. These IL‐27‐neutralized mice exhibited enhanced cellular and humoral immune responses and protection. These findings demonstrate that IL‐27, which is produced during the acute phase of malaria infection, inhibits the development of unique Th1 memory precursor CD4 + T cells, suggesting potential implications for the development of vaccines and other strategic interventions. Synopsis IL‐27 inhibits the generation of parasite‐specific memory CD4 + T cells in a malaria infection model. Transient blockade of IL‐27 elicits high levels of unique CD127 + and KLRG1 + memory CD4 + T cells, elevates antibody production, and enhances protective immunity against secondary infection. IL‐27 produced during the acute phase of malaria infection is inhibitory for the generation of parasite‐specific memory CD4 + T cells. Two types of unique memory CD4 + T cells are generated in the absence of IL‐27: CD127 + and KLRG1 + cells expressing high levels of Ifng and Tbx21, respectively. Memory CD4 + T cells induced in the absence of IL‐27 can be maintained in the absence of persistent malaria infection. The absence of IL‐27 during the acute phase of malaria infection generates memory immune responses that are protective against challenge infection. Graphical Abstract IL‐27 inhibits the generation of parasite‐specific memory CD4 + T cells in a malaria infection model. Transient blockade of IL‐27 elicits high levels of unique CD127 + and KLRG1 + memory CD4 + T cells, elevates antibody production, and enhances protective immunity against secondary infection.

In political philosophy, reflective equilibrium is a standard method used to systematically reconcile intuitive judgments with theoretical principles. In this paper, we propose that survey experiments and a model selection method—i.e., the Akaike Information Criterion (AIC)-based model selection method—can be viewed together as a methodological means of satisfying the epistemic desiderata implicit in reflective equilibrium. To show this, we conduct a survey experiment on two theories of distributive justice, prioritarianism and sufficientarianism. Our experimental test case and AIC-based model selection method demonstrate that the refined sufficientarian principle, a widely accepted principle of distributive justice, is no more plausible than the prioritarian principle. This tells us that some changes of certain intuitions revolving around sufficientarianism should be examined (separately) based on the findings of the survey experiment and AIC model selection. This shows the potential of our approach—both practically and methodologically—as a novel way of applying reflective equilibrium in political philosophy.

Difficulty in performing ureteroscopic lithotripsy (URSL) depends on endoscopic findings surrounding calculi. In this multicentre prospective cohort study of 185 patients with a single ureteral stone who underwent ureteroscopic lithotripsy registered in the SMART study between January 2014 and February 2017, we established a classification of endoscopic findings and analysed risk factors for ureteral changes. We evaluated endoscopic findings (oedema, polyps, ureteral mucosa-stone adherence, and distal ureteric tightness) based on the SMART classification. Operative time and ureteral injuries were significantly correlated with endoscopic finding grades. Multivariate analyses revealed that mucosa-stone adherence (MSA) was strongly affected by hydronephrosis grade (odds ratio, 12.4; p  = 0.022) and the interval before surgery (odds ratio, 1.10; p  = 0.012). The cutoff value for MSA was 98 days, with a predictive accuracy of 0.78. Risk factors for distal ureteric tightness were age (odds ratio, 0.96; p  = 0.004) and early intervention (odds ratio, 0.90; p  = 0.023). The cutoff value was 34 days, with a predictive accuracy of 0.72. In conclusion, appropriate intervention around 34 days (limited to 98 days) after symptom onset is necessary for treating ureteral calculi. Even if intervention passed 98 days post-symptom onset, staged URSL, alternative procedures, and detailed informed consent should be planned in advance, assuming strong MSA.

To conduct a retrospective multicenter trial to determine the significance of metastatic site as a predictor of nivolumab efficacy in patients with advanced non-small cell lung cancer. This study was conducted across three medical centers in Japan. We retrospectively reviewed all patients who commenced nivolumab treatment at these centers between December 17, 2015 and July 31, 2016. Clinical data were collected, including age, sex, smoking status, Eastern Cooperative Oncology Group performance status, and metastatic site (lymph nodes, liver, brain, bone, lungs [intrapulmonary metastasis], and malignant pleural effusion) at the time of commencing nivolumab treatment. Patients were followed-up until March 31, 2017. Two hundred and one patients were enrolled. The median age at the time of commencing nivolumab treatment was 68 (range, 27-87) years. One hundred and thirty-five patients were male, 157 patients had a history of smoking, 153 patients had a performance status of 0-1, and 42 patients had squamous cell carcinoma. The median progression-free survival of all patients was 2.5 months. In the univariate analysis, a performance status of ≥2 (hazard ratio [HR]: 1.89, 95.0% confidence interval [CI]: 1.33-2.69; p < 0.001) and liver (HR: 2.09, 95.0% CI: 1.35-3.25; p < 0.001) and lung (HR: 1.57, 95.0% CI: 1.14-2.16; p < 0.01) metastases correlated with a significantly shorter progression-free survival in nivolumab-treated patients. In the multivariate analysis, a performance status of ≥2 (HR: 1.54, 95.0% CI: 1.05-2.25; p < 0.05) and liver (HR: 1.90, 95.0% CI: 1.21-2.98; p < 0.01) and lung (HR: 1.41, 95.0% CI: 1.00-1.99; p < 0.05) metastases were independently correlated with a significantly shorter progression-free survival in nivolumab-treated patients. Liver and lung metastases and a poor performance status are independent predictors of nivolumab efficacy in patients with advanced non-small cell lung cancer.

Nucleosomes are dynamic entities that are repositioned along DNA by chromatin remodeling processes. A nucleosome repositioned by the switch-sucrose nonfermentable (SWI/SNF) remodeler collides with a neighbor and forms the intermediate “overlapping dinucleosome.” Here, we report the crystal structure of the overlapping dinucleosome, in which two nucleosomes are associated, at 3.14-angstrom resolution. In the overlapping dinucleosome structure, the unusual “hexasome” nucleosome, composed of the histone hexamer lacking one H2A-H2B dimer from the conventional histone octamer, contacts the canonical “octasome” nucleosome, and they intimately associate. Consequently, about 250 base pairs of DNA are left-handedly wrapped in three turns, without a linker DNA segment between the hexasome and octasome moieties. The overlapping dinucleosome structure may provide important information to understand how nucleosome repositioning occurs during the chromatin remodeling process.

It has been suggested that non-fasting triglyceride (TG) concentrations may be useful in predicting various diseases. However, current epidemiological evidence focuses mainly on the effects of fasting TG concentrations. The aim of this study was to investigate the effect of fasting and non-fasting TG levels on new-onset hyperuricemia (HUA) in the general Japanese population. This is a population-based retrospective cohort study (ISSA-CKD study); it included 5,576 participants without HUA at baseline between 2008 and 2019. Participants were categorized into gender-specific tertile groups of serum TG levels: group 1 (< 83 mg/dL [0.94 mmol/l] in male and < 77 mg/dL [0.87mmol/l] in female), group 2 (83-129mg/dL [0.94–1.46mmol/l] in male and 77-114 mg/dL [0.87–1.29mmol/l in female), and group 3 (≥ 130mg/dL [1.47 mmol/l] in male and ≥ 115 mg/dL [1.30mmol/l] in female). Outcome of this study was new-onset HUA (serum uric acid > 7 mg/dL [0.42 mmol/l]). During the 5.4-year follow-up period, 552 male and 146 female participants developed new-onset HUA. Incidence rates (per 1,000 person-years) of HUA were 18.2 in group 1, 21.9 in group 2 and 31.0 in group 3 among male, and 2.1 in group 1, 4.0 in group 2 and 7.4 group 3 among female. These associations remained significant after adjustment for confounders (p trend < 0.0001 among male and 0.0004 for female). There was no clear difference in effect of non-fasting and fasting TG levels on the development of new HUA (P interaction = 0.546 for male and 0.886 for female). Non-fasting and fasting TG concentrations were significantly associated with new-onset HUA among general Japanese men and women.

Genotyping of EGFR (epidermal growth factor receptor) mutations is indispensable for making therapeutic decisions regarding whether to use EGFR tyrosine kinase inhibitors (TKIs) for lung cancer. Because some cases might pose challenges for biopsy, noninvasive genotyping of EGFR in circulating tumor DNA (ctDNA) would be beneficial for lung cancer treatment. We developed a detection system for EGFR mutations in ctDNA by use of deep sequencing of plasma DNA. Mutations were searched in >100 000 reads obtained from each exon region. Parameters corresponding to the limit of detection and limit of quantification were used as the thresholds for mutation detection. We conducted a multi-institute prospective study to evaluate the detection system, enrolling 288 non-small cell lung cancer (NSCLC) patients. In evaluating the performance of the detection system, we used the genotyping results from biopsy samples as a comparator: diagnostic sensitivity for exon 19 deletions, 50.9% (95% CI 37.9%-63.9%); diagnostic specificity for exon 19 deletions, 98.0% (88.5%-100%); sensitivity for the L858R mutation, 51.9% (38.7%-64.9%); and specificity for L858R, 94.1% (83.5%-98.6%). The overall sensitivities were as follows: all cases, 54.4% (44.8%-63.7%); stages IA-IIIA, 22.2% (11.5%-38.3%); and stages IIIB-IV, 72.7% (60.9%-82.1%). Deep sequencing of plasma DNA can be used for genotyping of EGFR in lung cancer patients. In particular, the high specificity of the system may enable a direct recommendation for EGFR-TKI on the basis of positive results with plasma DNA. Because sensitivity was low in early-stage NSCLC, the detection system is preferred for stage IIIB-IV NSCLC.

γδ T cells facilitate the CD4 + T helper 1 (Th1) cell response against Plasmodium infection by activating conventional dendritic cells (cDCs), although the underlying mechanism remains elusive. Our study revealed that γδ T cells promote the complete maturation and production of interleukin-12 and CXCR3-ligands specifically in type 1 cDCs (cDC1), with minimal impact on cDC2 and monocyte derived DCs (Mo-DCs). During the initial infection phase, γδ T cell activation and temporal accumulation in the splenic white pulp, alongside cDC1, occur via CCR7-signaling. Furthermore, cDC1/γδ T cell interactions in the white pulp are amplified through CXCR3 signaling in γδ T cells, optimizing Th1 cell priming by cDC1. We also demonstrated how transitional Th1 cells arise in the white pulp before establishing their presence in the red pulp as fully differentiated Th1 cells. Additionally, we elucidate the reciprocal activation between γδ T cells and cDC1s. These findings suggest that Th1 cell priming is orchestrated by this reciprocal activation in the splenic white pulp during the early phase of blood-stage Plasmodium infection.