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Background: Pulmonary sarcomatoid carcinoma is a rare tumor that is resistant to cytotoxic agents. This observational study aimed to evaluate the detection rate of driver gene alteration and the efficacy of targeted therapy for pulmonary sarcomatoid carcinoma. Methods: We established a database of patients with pulmonary sarcomatoid carcinoma and their clinical information, including EGFR mutation, ALK fusion gene, ROS1 fusion gene, BRAF mutation, and MET exon 14 skipping mutation. The present study retrieved and analyzed the data of patients with pulmonary sarcomatoid carcinoma in whom driver gene alterations were evaluated, and the survival duration after the initiation of treatment with targeted therapy was examined. Results: A total of 44 patients were included in the present study. The EGFR mutation, ALK fusion gene, and MET exon 14 skipping mutation were detected in 2/43 patients (4.7%), 2/34 patients (5.9%), and 2/16 patients (12.5%), respectively. The ROS1 fusion gene (0/18 patients) and BRAF mutation (0/15 patients) were not detected. Female patients (P = 0.063, Fisher's exact test) and patients without smoking history (P = 0.025, Fisher's exact test) were the dominant groups in which any driver mutation was detected. Five patients with driver gene alterations were treated with targeted therapy. Progression-free survival (PFS) was 1.3 months and 1.6 months in 2 of the patients treated with gefitinib. Two patients with the ALK fusion gene showed 2.1 and 14.0 months of PFS from the initiation of treatment with crizotinib, and a patient with the MET exon 14 skipping mutation showed 9.7 months of PFS from the initiation of treatment with tepotinib. Conclusion: The EGFR mutation, ALK fusion gene, and MET exon 14 skipping mutation were detected in patients with pulmonary sarcomatoid carcinoma in clinical practice, and some patients achieved long survival times after receiving targeted therapy. Further investigation is necessary to evaluate the efficacy of targeted therapy for pulmonary sarcomatoid carcinoma. [ABSTRACT FROM AUTHOR]

While there is a large body of studies on reading motivation conducted in Western countries, little research compared college students' reading motivation between Western and Eastern Asian countries. It is unclear whether previous findings can be expanded from Western contexts to Eastern Asian contexts. This quantitative study explored the country and gender differences in reading motivation among 228 American (114 males and 114 females) and 228 Chinese (114 males and 114 females) college students. Our results showed that Chinese college students showed higher scores in two dimensions of reading motivation (reading as part of self and reading for recognition) than American students. We also found that there were similar scores in two other dimensions (reading efficacy and reading to do well in other realms), suggesting cross-cultural differences and similarities in reading motivation. Additionally, we found that male students exhibited higher scores than female students for reading efficacy while other dimensions remained invariant. This pioneer study highlights the important effects of country and gender on reading motivation. [ABSTRACT FROM AUTHOR]

The benefits of short-term inhalation of conifer aromas are well known, and their effects on the human body and mind in indoor work environments were evaluated. While physiological and mental health care is a major concern for many workers, and stress-coping interventions have been explored, there are few studies on the effects of stress reduction in the work environment by using conifer aroma. Therefore, this study aimed to investigate the effects of aroma use on psychophysiological stress reduction and work efficiency, focusing on the aromas of trees from the Cupressaceae. Two commercial essential oils were used in this experiment, and chemical compounds in the oils and volatile compounds in the experimental room air with and without each essential oil were analyzed by gas chromatography–mass spectrometer. The stress response scale was measured as a psychological indicator, while autonomic nervous system activity by heart rate variability analysis, and salivary oxytocin levels were measured as physiological indicators along with subjective questionnaires. In total, five simulated work tasks were used. The results showed that the components and their content in the air were different in the experimental room air with each essential oil. Furthermore, the aromas of one essential oil significantly reduced the helplessness scores psychologically, increased parasympathetic nervous system activity physiologically, and the other one significantly created a subjective impression that the aromas of the essential oils were pleasant. These results suggest that experimental participants became psychophysiologically relaxed while engaging in work. Therefore, the use of essential oils made mainly from Cupressaceae trees in the work environment may be useful in stress relief and promoting health benefits among workers. [ABSTRACT FROM AUTHOR]

This study aimed to examine whether Japanese participants condition spoken words' meanings to written pseudowords. In Survey 1, we selected spoken words associated with negative (α =.91) and positive (α =.79) features for Experiment 1 and passive (α =.90) and active (α =.80) features for Experiment 2. In Experiment 1, participants evaluated four written pseudowords' emotional valence using a 7-point semantic differential scale (1: negative; 7: positive) before and after conditioning spoken words with negative, neutral, or positive features to each pseudoword. In the conditioning phase, participants read each pseudoword, listened to a spoken word, and verbally repeated each spoken word. The results showed that a pseudoword was conditioned to spoken words with positive and negative features. In Experiment 2, participants evaluated four pseudowords' activeness using a 7-point semantic differential scale (1: passive; 7: active) before and after conditioning spoken words of passive, neutral, and active features to each written pseudoword. In the conditioning phase, the participants read each written pseudoword, listened to a spoken word, and repeated the spoken word. The results showed that the activeness evaluations were more increased for pseudowords conditioned to spoken words of active and neutral features after conditioning than before conditioning but were unchanged for a pseudoword conditioned to those with passive features before and after conditioning. Additonally, Survey 2's results showed that although the positiveness and activeness responses of the words used in Experiments 1 and 2 were controlled well, the lack of significant differences among positiveness responses of words may influence the evaluative conditioning in Experiment 2. That is, when participants condition passive (low arousal) words' activeness (arousal) ratings to those of pseudowords, words' positiveness (valence) ratings would be important in the evaluative conditioning. Our findings suggest that participants can condition spoken word meanings of preference and activeness to those of written pseudowords. It also indicates that linguistically evaluative conditioning's effects are robust in a non-alphabetic language. [ABSTRACT FROM AUTHOR]

Immune checkpoint inhibitors have significantly improved the prognosis in patients with non-small cell lung cancer, compared with cytotoxic agents. However, the prediction of treatment response is often difficult, even after assessing the tumor programmed death-ligand 1 expression. We conducted this observational study to analyze the association between the differentiation of peripheral CD4 + T cells and the efficacy of immune checkpoint inhibitor therapy. We enrolled patients who were diagnosed with non-small cell lung cancer and received immune checkpoint inhibitor therapy between 2020 and 2022. Blood samples were collected at the start of immune checkpoint inhibitor therapy, and the expressions of PD-1, CCR7, and CD45RA in peripheral CD4 + T cells were analyzed by flow cytometry. The association between the findings of flow cytometry and survival after the initiation of the immune checkpoint inhibitor therapy was evaluated. Forty patients with non-small cell lung cancer were enrolled. The Cox proportional hazards model showed that an increased proportion of CD45RA-CD4 + T cells was associated with a reduced risk of progression after adjustment for performance status, tumor programmed death-ligand 1 expression level, mutation status of the epidermal growth factor receptor gene, and combined therapy with cytotoxic agents. The present study showed that the proportion of peripheral CD45RA- CD4 + T cells was associated with progression-free survival after the initiation of immune checkpoint inhibitor therapy, independent of several clinical factors. [ABSTRACT FROM AUTHOR]

Long-acting injectable regimens for HIV treatment have been developed which are less frequent, more discreet, and more desirable for some people living with HIV (PLHIV) and may help reduce stigma-related barriers to HIV treatment. However, there is little information on the relationship between reported stigma and preference for these newer treatments. We characterized anticipated, experienced, and internalized HIV stigma and examined the associations with treatment preferences among an international sample of PLHIV. Data came from the international, web-based, cross-sectional study called "Positive Perspectives" conducted among PLHIV aged ≥ 18 years in 25 geographic locations during 2019 (n = 2389). Descriptive analyses were stratified among East Asian (n = 230) vs. non-Asian (n = 2159) participants. Results showed that prevalence of anticipated stigma was significantly higher among East Asian than non-Asian participants (72.2%[166/230] vs. 63.8%[1377/2159], p = 0.011). A significantly higher percentage of East Asian (68.7%[158/230]) than non-Asian participants (43.3%[935/2159] indicated that someone finding their HIV pills would cause them much "stress or anxiety" (p < 0.001). Actions taken by some PLHIV to prevent unwanted disclosure included restricting who they shared their HIV status with, hiding their HIV pills, or even skipping a dose altogether because of privacy concerns. Overall, 50.0%[115/230] East Asian participants believed HIV would reduce their lifespan and 43.0%[99/230] no longer planned for their old age because of HIV. Anticipated stigma was strongly associated with receptivity to non-daily regimens. Concerted efforts to reduce stigma and deliver flexible treatment options that address the unmet treatment needs of PLHIV, including confidentiality concerns, may improve their health-related quality of life. [ABSTRACT FROM AUTHOR]

Water recovery from Pt/Al2O3 catalyst combustion assisted by hydrogen is studied in two different systems. The hydrogen conversion rate and the resulting Pt-catalyst combustion temperature are measured over the reaction time. The Pt-catalyst combustion experiment is also performed using the hydrogen and oxygen produced by a PEM water electrolyzer. The recovered water is compared with the acceptable levels of elements in drinking water as defined by the World Health Organization (WHO). The hydrogen conversion rate reaches 100% after 20 min, and the maximum temperature increases with an increased H2/air feeding flow rate. Ion chromatographic analysis of the water resulting from the H2/air mixture contains four species (Li+, NH4+, K+, NO2−) with concentrations higher than the WHO standards. Moreover, the cation and anion analyses of the Pt-catalyst combustion using the PEM water electrolysis experiment agree with the WHO standards, except for lithium. [ABSTRACT FROM AUTHOR]

Non-infectious pulmonary complications (NIPCs) after allogeneic hematopoietic stem cell transplantation (HSCT) are associated with poor outcomes. It is important to maximize the effectiveness of primary treatment because secondary treatment has not been established. We analyzed data from 393 patients who underwent allogeneic HSCT during a 10-year period. Thirty-seven were diagnosed with NIPCs, which consisted of idiopathic pneumonia syndrome, bronchiolitis obliterans, and interstitial lung disease including cryptogenic organizing pneumonia. Among these, 18 died (Dead group) while 19 remained alive (Alive group) during the study period. The median time between NIPC diagnosis and first administration of ≥ 1 mg/kg/day corticosteroids (prednisolone dose equivalent) was significantly longer in the Dead group than the Alive group, at 9 days versus 4 days (p = 0.01). We further divided these cases into those who received prednisolone within seven days and after 8 days. We found that the ≤ 7 days group were more likely to survive after their NIPC diagnosis compared to the ≥ 8 days group (p = 0.06). Our analysis showed that early initiation of corticosteroid therapy is associated with long-term survival in NIPCs. [ABSTRACT FROM AUTHOR]

Spatial transcriptome analysis of formalin-fixed paraffin-embedded (FFPE) tissues using RNA-sequencing (RNA-seq) provides interactive information on morphology and gene expression, which is useful for clinical applications. However, despite the advantages of long-term storage at room temperature, FFPE tissues may be severely damaged by methylene crosslinking and provide less gene information than fresh-frozen tissues. In this study, we proposed a sensitive FFPE micro-tissue RNA-seq method that combines the punching of tissue sections (diameter: 100 μm) and the direct construction of RNA-seq libraries. We evaluated a method using mouse liver tissues at two years after fixation and embedding and detected approximately 7000 genes in micro-punched tissue-spots (thickness: 10 μm), similar to that detected with purified total RNA (2.5 ng) equivalent to the several dozen cells in the spot. We applied this method to clinical FFPE specimens of lung cancer that had been fixed and embedded 6 years prior, and found that it was possible to determine characteristic gene expression in the microenvironment containing tumor and non-tumor cells of different morphologies. This result indicates that spatial gene expression analysis of the tumor microenvironment is feasible using FFPE tissue sections stored for extensive periods in medical facilities. [ABSTRACT FROM AUTHOR]

Late-onset noninfectious pulmonary complications (LONIPC) are a major cause of morbidity and mortality after allogeneic hematopoietic stem cell transplantation (HSCT). However, the clinical impact of lung function deterioration itself in long-term adult survivors of HSCT remains to be fully investigated. This retrospective, longitudinal study aimed to investigate pulmonary function following HSCT in terms of its change and the clinical significance of its decline. We examined 167 patients who survived for at least 2 years without relapse. The median follow-up period was 10.3 years. A linear mixed-effects model showed that the slope of pulmonary function tests values, including percent vital capacity (%VC), percent forced expiratory volume in one second (%FEV1), and FEV1/forced VC ratio (FEV1%), decreased over time. The cumulative incidence of newly obstructive and restrictive lung function impairment (LFI) at 10 years was 15.7% and 19.5%, respectively. Restrictive LFI was a significant, independent risk factor for overall survival (hazard ratio 7.11, P = 0.007) and non-relapse mortality (hazard ratio 12.19, P = 0.003). Our data demonstrated that lung function declined over time after HSCT and that the decline itself had a significant impact on survival regardless of LONIPC. [ABSTRACT FROM AUTHOR]

Bites by elapid snakes (e.g. cobras) can result in life-threatening paralysis caused by venom neurotoxins blocking neuromuscular nicotinic acetylcholine receptors. Here, we determine the cryo-EM structure of the muscle-type Torpedo receptor in complex with ScNtx, a recombinant short-chain α-neurotoxin. ScNtx is pinched between loop C on the principal subunit and a unique hairpin in loop F on the complementary subunit, thereby blocking access to the neurotransmitter binding site. ScNtx adopts a binding mode that is tilted toward the complementary subunit, forming a wider network of interactions than those seen in the long-chain α-Bungarotoxin complex. Certain mutations in ScNtx at the toxin-receptor interface eliminate inhibition of neuronal α7 nAChRs, but not of human muscle-type receptors. These observations explain why ScNtx binds more tightly to muscle-type receptors than neuronal receptors. Together, these data offer a framework for understanding subtype-specific actions of short-chain α-neurotoxins and inspire strategies for design of new snake antivenoms. Bites by elapid snakes can result in life-threatening paralysis caused by α-neurotoxins blocking the neuromuscular nicotinic acetylcholine receptor. Here, the authors determine the cryo-EM structure of this receptor in complex with a short-chain α-neurotoxin. [ABSTRACT FROM AUTHOR]

Aging societies are a global problem, necessitating the promotion of well-being in healthy older adults. However, the evidence regarding psychological interventions in this population is unclear. Therefore, we conducted a systematic review and metaanalysis to clarify the effects of psychological interventions on the well-being of healthy older adults. A systematic literature search was performed using PubMed, PsycINFO, and CiNii. Included studies were randomized controlled trials of psychological interventions designed to improve psychological well-being in healthy older adults. The search yielded 1,047 articles, out of which five qualitative and four quantitative studies were selected. A meta-analysis was performed using a random effects model. We found a large effect size (Hedges' g = 0.87) and heterogeneity among the studies (I2 = 94.4%, τ2 = 0.556, p = 0.00). Most studies were evaluated as being of a low quality. There were five types of interventions: an isolation prevention program, outdoor activities, art therapy through participating in theater workshops, animal-assisted activity, and an encounter group. The results indicated that healthy older adults' psychological well-being can be promoted through interventions. The evaluated studies had no theoretical commonality; however, all research involved interaction with other people or animals. Thus, we recommend increased interaction with people or animals to promote well-being in older adults. Heterogeneity is a limitation of the study, and there is a need for more high-quality studies on well-being in healthy older adults. [ABSTRACT FROM AUTHOR]

Self-construal refers to how individuals view themselves independently from others (Independent self-construal) or interdependently with others (Interdependent self-construal). Although the self-construal theory claimed a connection between self-construal and motivation, none of studies explored the relation between self-construal and reading motivation. To bridge the gap, this study examined country and gender differences in self-construal and reading motivation of 236 Hispanic American and 114 Japanese college students. Additionally, we investigated the relation between self-construal and reading motivation. Our data indicated that country and gender modulated reading motivation, particularly reading efficacy. Furthermore, self-construal significantly predicted reading motivation regardless of country or gender. Specifically, Hispanic American and Japanese students with higher independence showed higher reading efficacy, whereas students with higher interdependence exhibited lower reading efficacy. This is the first study to reveal the close relation between self-construal and reading motivation in the field of education. [ABSTRACT FROM AUTHOR]

We examined satisfaction and perceived challenges with antiretroviral therapy (ART) among people living with HIV (PLHIV) in Japan vs three other Asian countries (China, Taiwan, South Korea), and 21 non-Asian countries, using data from the 2019 Positive Perspectives Study (pooled sample size from all 25 countries = 2389). Participants in other Asian countries were more likely than those in Japan to report they missed ART ≥ 1 time in the past month because they were depressed/overwhelmed (57.4%[89/155] vs 32.0%[24/75]), had privacy concerns (56.8%[88/155] vs 30.7%[23/75]), were concerned about the potential long-term negative impacts of ART (46.5%[72/155] vs 26.7%[20/75]), or just wanted to forget about HIV (45.8%[71/155] vs 22.7%[17/75]). ART satisfaction however did not differ significantly between surveyed PLHIV in Japan (54.7%[41/75]) vs those in other Asian countries (47.7%[74/155]). The percentage who felt that daily ART dosing limited their lives was 36.0%[27/75] among participants from Japan, 48.4%[75/155] among participants from other Asian countries, and 27.3%[589/2159] among those from non-Asian countries. Within a structural equation model using pooled data from all 25 countries, positive correlations were seen between ART satisfaction and "provider engagement" (β = 0.35), high perceived control over ART dosing schedule (β = 0.28), and the belief that ART prevents HIV transmission (β = 0.16). Conversely, negative correlations were seen between ART satisfaction and experience of ART side-effects (β = − 0.24), high "ART anxiety" (β = − 0.20); and being on multi-tablet regimens (β = − 0.13). Those ART-satisfied reported higher self-rated health and greater ART adherence. These findings underscore the need for patient-centered care to enhance treatment satisfaction and improve ART adherence. [ABSTRACT FROM AUTHOR]

Background: The patients with ruptured vertebral artery dissecting aneurysm (rVADA) should be treated as early as possible because VADA carries extremely high risk of rebleeding in the acute phase. We have established a mobile endovascular strategy for the patients with rVADA between our flagship center and its affiliated local hospitals. We introduced and reviewed our mobile endovascular therapy in this study. Methods: We retrospectively evaluated 98 consecutive patients who underwent endovascular surgery for rVADA from 2000 to 2018 at our institution or five affiliated hospitals. When each patient was initially transported to the local affiliated hospitals, neuroendovascular surgeons traveled directly to the affiliated hospital from the flagship center in order to treat the patient there. Clinical outcomes using modified Rankin Scale at 6 months after treatment, radiological results, and procedure-related complications were reviewed to justify our mobile endovascular strategy. Results: All aneurysms were cured successfully by internal trapping. Favorable outcome was achieved in 61 patients (62.2%) even though 53 patients (54.1%) had presented with severe subarachnoid hemorrhage. Overall mortality rate, treatment-related mortality rate, and treatment related complication rate were 18.4% (18/98), 0%, and 16% (16/98), respectively. There were no differences in clinical and radiological outcomes between the patients treated in the flagship center and those who treated in the affiliated hospitals. Treatment in the affiliated hospital was not a predictive factor of unfavorable outcome in our multivariate analysis, and elderly age (≥ 60) was negatively associated with favorable outcome. Conclusions: Our results prove the efficacy and safety of mobile endovascular therapy for the treatment of rVADA in the ultra-acute stage. Mobile endovascular therapy may work well in the acute treatment of rVADAs in the certain circumstance. [ABSTRACT FROM AUTHOR]

Background: Bronchiolitis obliterans syndrome (BOS) remains one of the most devastating manifestations of chronic graft-versus-host disease in hematopoietic cell transplantation (HCT). Recent findings of BOS after lung transplantation indicate that donor (lung)-derived lung-resident macrophages contribute to BOS, suggesting that differences in the origin of immune cells and localized antigen-presenting cells cause the onset of BOS. Methods: We identified the phenotype and origin of infiltrating macrophages using immunohistochemistry and fluorescence in situ hybridization in eight sex-mismatched HCT recipients who underwent lung transplantation for BOS after HCT. Results: Most of the infiltrating macrophages appeared to be derived from donor (hematopoietic) cells in patients who developed BOS following HCT. Macrophages observed in the early-stage region of BOS were positive for cluster of differentiation (CD)68 and inducible nitric oxide synthase (iNOS) and negative for CD163 and CD206, suggesting an M1 phenotype. In the late-stage region, macrophages were negative for CD68 and iNOS in all patients, but also positive for CD163 and CD206 in some patients. Conclusions: Donor-derived M1-macrophages may be involved in the pathogenesis of the early-stage region of BOS. In addition, some macrophages in the late-stage region showed M2 polarization that might be involved in fibrosis. [ABSTRACT FROM AUTHOR]

Background: Emergency appendectomy is often performed for de Garengeot hernia. However, in some cases, there may be a chance to perform an appendix-preserving elective surgery. Case description: A 76-year-old woman presented to our hospital with complaints of a right inguinal swelling, which we diagnosed as a de Garengeot hernia using computed tomography (CT). B-mode ultrasonography (US) of the mass showed an appendix 4–6 mm in diameter with a clear wall structure; color Doppler US showed pulsatile blood flow signal in the appendiceal wall. Twenty-eight days later, herniorrhaphy with transabdominal preperitoneal repair (TAPP) was performed without appendectomy. Another 70-year-old woman presented to our hospital with complaints of a painful bulge in the right inguinal region. The diagnosis of de Garengeot hernia was made using CT. B-mode US showed an appendix 5 mm in diameter with a clear wall structure. Color Doppler US showed a pulsatile blood signal in the appendiceal wall. Seven days later, herniorrhaphy with TAPP was performed without appendectomy. Conclusion: De Garengeot hernia is often associated with appendicitis; however, an appendix-preserving elective herniorrhaphy can be performed if US and intraoperative findings do not suggest appendicitis or circulatory compromise in the appendix. [ABSTRACT FROM AUTHOR]

Candida albicans is the most common cause of fungal sepsis. Inhibition of inflammasome activity confers resistance to polymicrobial and LPS-induced sepsis; however, inflammasome signaling appears to protect against C. albicans infection, so inflammasome inhibitors are not clinically useful for candidiasis. Here we show disruption of GSDMD, a known inflammasome target and key pyroptotic cell death mediator, paradoxically alleviates candidiasis, improving outcomes and survival of Candida-infected mice. Mechanistically, C. albicans hijacked the canonical inflammasome-GSDMD axis-mediated pyroptosis to promote their escape from macrophages, deploying hyphae and candidalysin, a pore-forming toxin expressed by hyphae. GSDMD inhibition alleviated candidiasis by preventing C. albicans escape from macrophages while maintaining inflammasome-dependent but GSDMD-independent IL-1β production for anti-fungal host defenses. This study demonstrates key functions for GSDMD in Candida's escape from host immunity in vitro and in vivo and suggests that GSDMD may be a potential therapeutic target in C. albicans-induced sepsis. Inflammasome signalling has been shown to protect Candida albicans during infection and as such limits inflammasome inhibitors in this context. Here the authors implicate Gasdermin D in C.ablicans immune evasion and suggests its targeting therapeutically. [ABSTRACT FROM AUTHOR]

Si nanowires/nanorods are known to enhance the cycle performance of the lithium-ion batteries. However, viable high throughput production of Si nanomaterials has not yet attained as it requires in general expensive gas source and low-rate and multiple-step approach. As one of the potential approaches, in this work, we report the fast-rate Si nanorod synthesis from low-cost powder source by the modified plasma flash evaporation and the fundamental principle of structural formation during gas co-condensation. In this process, while Si vapors are formed in high temperature plasma jet, molten copper droplets are produced separately at the low temperature region as catalysts for growth of silicon nanorods. Si rods with several micrometers long and a few hundred of nanometers in diameter were produced in a single process at rates up to 40 µm s−1. The growth of the Si nanorods from powder source is primarily characterized by the vapor–liquid–solid growth which is accelerated by the heat extraction at the growth point. The battery cells with the Si nanorods as the anode have shown that a higher capacity and better cyclability is achieved for the nanorods with higher aspect ratios. [ABSTRACT FROM AUTHOR]

Purpose: To examine the incidence of and risk factors for deep vein thrombosis (DVT) among different types of osteotomies around the knee. It was hypothesized that DVT would be detected at a substantial rate after the osteotomy, and there would be differences in the incidences among the different osteotomy procedures. Methods: Consecutive patients who underwent knee osteotomies for varus osteoarthritis and met the inclusion criteria were included in the study. Ultrasonographic evaluation was performed to detect DVT on bilateral whole leg at 1 month before and 7 days after surgery. Statistical comparison of the demographic and clinical parameters between the patients with and without DVT as well as multivariate analysis using logistic regression was conducted to identify risk factors related to the incidence of postoperative DVT. Results: The study subjects comprised 159 knees in 135 patients with medial opening wedge high tibial osteotomy (MOW-HTO), 93 knees in 78 patients with lateral closed wedge high tibial osteotomy (LCW-HTO), and 74 knees in 54 patients with double level osteotomy (DLO). In the postoperative evaluation, DVT was detected in 19 of 159 knees (11.9%) in MOW-HTO, 21 of 93 knees (22.6%) in LCW-HTO, and 5 of 74 knees (6.8%) in DLO. The incidence of DVT was significantly higher after LCW-HTO than after MOW-HTO and DLO (p < 0.01). DVT at a level above the knee was noted in one case after MOW-HTO, while DVT in the remaining cases developed at a level below the knee. No cases of symptomatic pulmonary embolism were encountered during the study period. Among the potential risk factors assessed for correlation with the incidence of DVT, LCW-HTO was identified as a significant risk factor (odds ratio: 2.54; 95% CI 1.334–4.836; p < 0.01). Conclusions: This study demonstrated that DVT occurred at a substantial rate (overall incidence of 13.8%) after osteotomy around the knee even with the use of prophylactic anticoagulant. Among the different osteotomy types, the DVT rate was significantly higher after LCW-HTO than after MOW-HTO and DLO. Level of evidence: Prospectively designed observational cohort study, Level III. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of this study was to examine the radiological features of hinge fracture occurring at the distal medial femoral cortex in knees undergoing biplanar lateral closed-wedge distal femoral osteotomy (LCW-DFO) in double-level osteotomy (DLO) based on pre- and postoperative CT image analyses. It was hypothesised that medial hinge fractures in LCW-DFO would occur with a similar incidence to that in high tibial osteotomy, and its occurrence would affect the clinical/radiological outcomes and induce unintended change in alignment depending on the fracture type (direction of the fracture). Methods: A consecutive series of 36 knees (31 patients) with primary varus osteoarthritis undergoing DLO comprised the study population. The mean age at surgery was 62.0 ± 5.9 years. Presence of hinge fracture was assessed on radiographs and CT images at 1 week. The fracture type was classified depending on the direction of the fracture line: crack propagation in line with the osteotomy (type 1) and fractures extending proximally (type 2) or distally (type 3) from the tip of the wedge. Computer-assisted assessments of bony limb alignment and bony geometry were conducted on a full-length weight-bearing radiograph and CT images using image analysis software. In addition, subjective clinical results were evaluated using the Knee Injury and Osteoarthritis Outcome Score (KOOS). Radiological and clinical follow-up results at 1 and 2 years were compared to the preoperative data, while comparative analysis was made between the subjects with and without a hinge fracture. Results: Postoperative image examinations revealed type 1 and 2 medial femoral hinge fractures in 4 and 7 knees, while no type 3 fracture was identified in the study population. Consequently, the overall incidence of the hinge fracture was 30.6% (11 of the 36 knees). Four of those 11 fractures (36.4%) could not be detected on plain radiographs. CT image analysis for three-dimensional bony geometry showed greater increase in internal rotation of the distal bony segment (increased femoral antetorsion by 9.5° on average) after surgery compared to the knees without a hinge fracture (P = 0.01). Clinical evaluation using the KOOS at 2 years showed no significant difference between the groups with and without hinge fractures. Conclusion: In LCW-DFO, medial femoral hinge fractures occurred in 30.6% of the cases. Knees with type 1 hinge fracture exhibited significantly greater increase in femoral antetorsion as compared to those without hinge fracture. In this case series, postoperative weight-bearing protocol was delayed for knees with hinge fracture. Consequently, surgical results were not affected by the occurrence of hinge fracture for up to 2 years. Level of evidence: IV (case series) [ABSTRACT FROM AUTHOR]

Sound symbolic words consist of inevitable associations between sounds and meanings. We aimed to identify differences in familiarity, visual imageability, auditory imageability, tactile imageability, emotional valence, and arousal between Japanese sound symbolic words with voiced initial consonants (VCs; dakuon in Japanese; e.g., biribiri) and Japanese sound symbolic words with semi-voiced initial consonants (SVCs; handakuon in Japanese; e.g., piripiri), and between VCs (e.g., daradara) and Japanese sound symbolic words with voiceless initial consonants (VLCs; seion in Japanese; e.g., taratara). First, auditory imageability and arousal were significantly higher in VCs than SVCs, whereas familiarity, tactile imageability, and positive emotion (emotional valence) were significantly higher in SVCs than VCs. Second, visual imageability was higher in VCs than VLCs, while familiarity and positive emotion were higher in VLCs than VCs. Initial consonants in Japanese sound symbolic words could be associated with specific subjective evaluations such as familiarity, visual imageability, auditory imageability, tactile imageability, emotional valence, and arousal. [ABSTRACT FROM AUTHOR]

This correction notice is for an article titled "The molecular mechanism of snake short-chain α-neurotoxin binding to muscle-type nicotinic acetylcholine receptors" published in Nature Communications. The correction addresses an omission in the Acknowledgements section, where two funding sources were mistakenly left out. The correction has been made in both the PDF and HTML versions of the article. The authors of the article are Mieke Nys, Eleftherios Zarkadas, Marijke Brams, Aujan Mehregan, Kumiko Kambara, Jeroen Kool, Nicholas R. Casewell, Daniel Bertrand, John E. Baenziger, Hugues Nury, and Chris Ulens. [Extracted from the article]

Previous studies have found that rumination involves thoughts that usually occur during and influence affect after experiencing failure. However, little is known about how rumination directly affects approach behavior beyond that point. Therefore, we investigated the effects of rumination on approach behavior after failure. Forty-nine university students were allocated to one of either an abstract or concrete processing mode of rumination or a control condition. A failure experience was induced through a creative thinking task, and rumination was either manipulated or not depending on the group. The students then performed a task that was similar to the failure-inducing creative thinking task. Our analysis revealed that only the concrete processing mode of rumination improved participants' negative affect and that the manipulation of rumination ultimately did not influence approach behavior after experiencing failure. [ABSTRACT FROM AUTHOR]

The transmission performance of spatial multiplexing cross-polarized MIMO is studied to determine how to increase the capacity of digital terrestrial broadcasting and make it more robust. In this paper, the performance was evaluated in laboratory experiments and large-scale field experiments in central Tokyo under three deployment scenarios. The results showed that the required received power can be improved by 7.3 dB when MIMO is introduced to enhance transmission robustness, i.e., maintaining the same transmission capacity as SISO. Alternatively, the transmission capacity can be doubled by introducing MIMO for the same robustness as SISO, requiring a slight increase in received power of 0.9 dB compared with SISO. The field experiments were performed by using a prototype transmission system for advanced digital terrestrial TV broadcasting in Japan, but the results obtained are also valid for 5G broadcasting. Regarding the feasibility of the advanced terrestrial broadcasting system operating at a target bit rate of about 60 Mbps to distribute a VVC-based 8 K program within a 6-MHz channel bandwidth, an increased received power of 3.7 dB compared with SISO was required for MIMO to achieve a higher transmission capacity in the worst case for 28 reception points evaluated in urban areas. [ABSTRACT FROM AUTHOR]

In Pseudomonas aeruginosa the alp system encodes a programmed cell death pathway that is switched on in a subset of cells in response to DNA damage and is linked to the virulence of the organism. Here we show that the central regulator of this pathway, AlpA, exerts its effects by acting as an antiterminator rather than a transcription activator. In particular, we present evidence that AlpA positively regulates the alpBCDE cell lysis genes, as well as genes in a second newly identified target locus, by recognizing specific DNA sites within the promoter, then binding RNA polymerase directly and allowing it to bypass intrinsic terminators positioned downstream. AlpA thus functions in a mechanistically unusual manner to control the expression of virulence genes in this opportunistic pathogen. In Pseudomonas aeruginosa, the protein AlpA activates the expression of the alp locus in response to DNA damage, leading to lysis in a subset of cells and enhancing virulence of other, surviving cells. Here, the authors show that AlpA acts as an antiterminator rather than a transcriptional activator. [ABSTRACT FROM AUTHOR]

The left prefrontal cortex is essential for verbal communication. It remains uncertain at what timing, to what extent, and what type of phrase initiates left-hemispheric dominant prefrontal activation during comprehension of spoken sentences. We clarified this issue by measuring event-related high-gamma activity during a task to respond to three-phrase questions configured in different orders. Questions beginning with a wh-interrogative deactivated the left posterior prefrontal cortex right after the 1st phrase offset and the anterior prefrontal cortex after the 2nd phrase offset. Left prefrontal high-gamma activity augmented subsequently and maximized around the 3rd phrase offset. Conversely, questions starting with a concrete phrase deactivated the right orbitofrontal region and then activated the left posterior prefrontal cortex after the 1st phrase offset. Regardless of sentence types, high-gamma activity emerged earlier, by one phrase, in the left posterior prefrontal than anterior prefrontal region. Sentences beginning with a wh-interrogative may initially deactivate the left prefrontal cortex to prioritize the bottom-up processing of upcoming auditory information. A concrete phrase may obliterate the inhibitory function of the right orbitofrontal region and facilitate top-down lexical prediction by the left prefrontal cortex. The left anterior prefrontal regions may be recruited for semantic integration of multiple concrete phrases. [ABSTRACT FROM AUTHOR]

Purpose: We hypothesized that patient treated with OWHTO who participate in high-impact sports would attain satisfactory outcome. The purpose of this study was to examine the clinical and radiological outcomes in a consecutive series of opening-wedge high tibial osteotomy (OWHTO) in highly active patients. Methods: Seventy-seven consecutive patients who underwent OWHTO with varus osteoarthritic knees were included in the study. The mean age of the study population was 56.1 years. All patients were followed for a minimum of 2 years. Clinical and radiological evaluations were performed at 12 and 24 months after surgery. The clinical results were evaluated using the Knee Injury and Osteoarthritis Outcome Score (KOOS) and the International Knee Documentation Committee (IKDC) Subjective Score. In regards to radiological assessment, the following parameters were measured in full-length weightbearing radiographs both pre- and postoperatively; mechanical tibiofemoral angle (mTFA), mechanical lateral distal femoral angle (mLDFA), and weight bearing line (WBL) ratio. Results: Fifty-eight patients (75.3%) returned to the same high-impact sports activities as before surgery, with a mean time to return of 8.7 ± 2.7 months (6–14 months). In the clinical assessments, the IKDC subjective score and KOOS both improved from the mean preoperative scores of 38.4 and 217.4 points to the mean postoperative scores of 74.5 and 421.6 points, respectively. The mean pre-symptomatic Tegner activity scale was 5.3 ± 0.6 and significantly decreased to 4.8 ± 1.2 at 2 years postoperative (p < 0.05). In the radiological evaluation, the postoperative mTFA, mMPTA, and WBL ratio values averaged 1.3° ± 2.2° valgus, 90.7° ± 2.9°, and 51.6% ± 8.4°, respectively, at 24 months after surgery. Conclusions: Clinical outcomes based on postoperative patient-reported outcome measures and rate of return to high-impact sports activities were favorable after OWHTO in patients with knee OA who desired to continue sporting activities with the Tegner activity score of ≥ 5 points. Level of evidence: Retrospective case series, IV. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of this study was to examine the results of meniscal repair performed for symptomatic degenerative medial meniscal tears. Methods: Twenty-four knees in 24 patients with symptomatic degenerative medial meniscal tears (mostly complex horizontal tears) who underwent isolated arthroscopic repair combined with autologous fibrin clot implantation were included in this study. The patients were followed up for a minimum of 2 years. The overall clinical outcome was evaluated using the Lysholm score, while the activity level was graded on the Tegner Activity Scale. The assessment of healing status at the repair site was based on clinical signs/symptoms and follow-up MRI examination results. In addition, the effects of the patient's clinical and radiological factors on healing of the repaired menisci were analyzed. Results: The mean age of the study subjects was 47.0 ± 8.1 years with a mean follow-up period of 39.3 ± 11.6 months. The Lysholm score significantly improved after surgery (P < 0.01). During the follow-up period, meniscal repairs were deemed to have failed in 6 of the 24 knees (25%). In the analysis of factors influencing meniscal healing, varus deformity (% of mechanical axis < 30%) was identified in all knees in the repair failure group, and the presence of varus deformity was shown to be a significant risk factor correlated with repair failure, while other factors did not significantly influence the healing status. Conclusions: The short-term follow-up results showed that arthroscopic repair of degenerative medial meniscal tears combined with fibrin clot implantation attained clinical healing in 18 of 24 knees (75%) of patients, while 6 of the 24 knees (25%) of patients experienced clinical failure. The presence of varus deformity negatively affects the healing rate. In well-aligned knees, degenerative medial meniscal tears are successfully treated by isolated repair with fibrin clot implantation. Level of evidence: IV. [ABSTRACT FROM AUTHOR]

People occasionally use filler phrases or pauses, such as "uh", "um", or "y'know," that interrupt the flow of a sentence and fill silent moments between ordinary (non-filler) phrases. It remains unknown which brain networks are engaged during the utterance of fillers. We addressed this question by quantifying event-related cortical high gamma activity at 70–110 Hz. During extraoperative electrocorticography recordings performed as part of the presurgical evaluation, patients with drug-resistant focal epilepsy were instructed to overtly explain, in a sentence, 'what is in the image (subject)', 'doing what (verb)', 'where (location)', and 'when (time)'. Time–frequency analysis revealed that the utterance of fillers, compared to that of ordinary words, was associated with a greater magnitude of high gamma augmentation in association and visual cortex of either hemisphere. Our preliminary results raise the hypothesis that filler utterance would often occur when large-scale networks across the association and visual cortex are engaged in cognitive processing, including lexical retrieval as well as verbal working memory and visual scene scanning. [ABSTRACT FROM AUTHOR]

Background: Factor-Xa inhibitors (FXaIs) are widely used for the treatment of non-valvular atrial fibrillation (NVAF). Although we have previously reported the distribution of the anti-factor Xa activity (AXA) values of three different FXaIs in NVAF patients, the differences in the distribution of AXA values among the different FXaIs in patients with renal impairment (RI) have not been fully elucidated. Methods: Trough and peak AXA values were measured in 94 patients taking rivaroxaban, 124 patients taking apixaban, and 66 patients taking edoxaban. Of them, we identified 26 patients with moderate RI [creatinine clearance (CrCl) 30–49 mL/min] and 17 patients with severe RI (CrCl 15–29 mL/min) in the rivaroxaban cohort, 37 patients with moderate RI and 17 patients with severe RI in the apixaban cohort, and 21 patients with moderate RI and 9 patients with severe RI in the edoxaban cohort. AXA values were measured using chromogenic AXA assays. Both trough and peak AXA values were compared between patients with moderate RI and those with severe RI in each cohort, and differences in the peak-to-trough ratio among the different drugs were assessed. Results: In the rivaroxaban cohort, the peak AXA value was significantly higher in patients with severe RI than in those with moderate RI. In the apixaban cohort, neither the trough nor peak AXA values significantly differed between patients with moderate RI and those with severe RI. In the edoxaban cohort, the trough AXA value was significantly higher in patients with severe RI than in those with moderate RI, and peak AXA tended to be higher in patients with severe RI. The peak-to-trough ratio of AXA values was significantly lower in patients taking apixaban than in those taking rivaroxaban and edoxaban. Conclusion: Among Japanese NVAF patients with RI, the peak or trough AXA values were higher in patients with severe RI than in those with moderate RI when taking rivaroxaban and edoxaban, whereas both the peak and trough AXA values were similar between patients with severe RI and those with moderate RI when taking apixaban. The peak-to-trough ratio of AXA values was the lowest in patients taking apixaban. [ABSTRACT FROM AUTHOR]

Background: Increased expression of programmed cell death 1 ligand 1 (PD-L1) by tumor cells is thought to be a mechanism through which solid cancers promote immune tolerance. However, the association between PD-L1 expression and the prognosis of upper urinary tract urothelial carcinoma (UTUC) remains unknown. Methods: We examined immunohistochemical PD-L1 expression and the tumor-infiltrating lymphocyte density (TILD) in 79 patients with UTUC who underwent nephroureterectomy. We classified the tumors into four types based on the combination of PD-L1 expression and TILD, and studied the clinicopathological characteristics of these four tumor types. Results: Elevated expression of PD-L1 by tumor cells and a higher TILD were associated with a worse histological grade, higher pT stage, and higher peripheral blood neutrophil-to-lymphocyte ratio. Elevated expression of PD-L1 by tumor cells, a higher TILD, and type I, III, or IV tumors with elevated expression of either PD-L1 or TILD showed a positive correlation with poorer differentiation and local invasion. These three variables were associated with shorter progression-free survival and overall survival in univariate analysis, but only the latter was an independent determinant according to multivariate analysis. The patients who had type II tumors with lower PD-L1 expression and a lower TILD showed more favorable survival than the other three groups. Conclusions: These findings suggest that PD-L1 expression and TILs in the tumor microenvironment influence the progression of UTUC. Accordingly, it is important to understand the immunologic characteristics of the tumor microenvironment to develop more effective treatment strategies for this cancer. [ABSTRACT FROM AUTHOR]

Background: Previous studies indicated inverse relationships between body mass index (BMI), diabetes and prostate-specific antigen (PSA) concentration besides an established positive relationship between age and PSA. Other causal relationships between clinical parameters including hypertension, hepatic function, tests, lipid profile and PSA were also suggested. Thus, we incorporated these parameters all together into the analysis to identify possible determinants of PSA concentration to improve the accuracy of PSA tests. Methods: Associations between PSA and the above-mentioned clinical parameters were examined among 14,486 men who visited our hospital for a routine health checkup, using linear regression analyses. Results: Total of 1403 (9.7%) and 784 (5.4%) men were classified as diabetes and obesity, respectively. After adjusting age, significant PSA reductions were found in diabetic men, especially for men taking antidiabetics. Such association was seen when the diabetic status was represented by hemoglobin A1c (HbA1c) and fasting blood sugar (FBS) levels. That is, PSA levels were significantly reduced in men with higher HbA1c and FBS levels. Obesity was also associated with a reduction in PSA levels. Moreover, PSA levels were significantly decreased with increased ALT levels. Conclusions: PSA test results should be carefully interpreted especially for men with diabetes and obesity, in whom a substantial reduction in PSA concentration is likely to occur. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of this study was to examine early radiological and clinical outcomes following minimally invasive double level osteotomy (DLO) procedure performed for osteoarthritic knees with severe varus deformity.Methods: Twenty consecutive patients who underwent DLO for varus osteoarthritic knees were included in the study. All patients could be tracked for a minimum of 1 year. Periodical radiological and clinical evaluations were performed at 6 and 12 months after surgery. In the radiological assessment, the following parameters were measured on full-length weight-bearing radiographs both pre- and postoperatively: mechanical tibiofemoral angle (mTFA), mechanical lateral distal femoral angle (mLDFA), mechanical medial proximal tibial angle (mMPTA), and joint-line convergence angle (JLCA). In addition, subjective clinical results were evaluated using the Knee Injury and Osteoarthritis Outcome Score (KOOS) and the International Knee Documentation Committee (IKDC) Subjective Score.Results: The mean age of the study population was 62.5 ± 6.8 years (range 45-76 years). In the radiological evaluation, the preoperative mTFA, mLDFA, mMPTA, and JLCA values averaged 13.5° ± 3.1° varus, 91.1° ± 1.4°, 82.3° ± 2.0°, and 5.8° ± 2.3°, respectively. At 6 and 12 months, all of the radiological parameters significantly improved and corrected to the values within normal range. In the clinical assessments at the follow-up evaluations, both the KOOS and IKDC subjective scores significantly improved from the preoperative values. No significant changes were noted between the 6 and 12-month results in the radiological and clinical assessments.Conclusions: The minimally invasive DLO technique is a valuable surgical technique accomplishing restoration of physiologic knee joint alignment and orientation with significant improvement in patient-registered clinical outcomes in early postoperative evaluation. Although the follow-up period is still short, the excellent clinical and radiological outcomes shown in the present study support the efficacy of this procedure.Level Of Evidence: Retrospective case series, Level IV. [ABSTRACT FROM AUTHOR]

Humans can increase the endpoint stiffness of their arm to reduce self-generated movement variability and to reject unpredictable perturbations from the environment, like during handheld drilling, thereby increasing movement precision. Existing methods to estimate changes in the endpoint stiffness use robotic interfaces to apply position or force perturbations to measure the arm's dynamic response. We propose an alternative method of measuring changes in the power grasp force to estimate adaptations in the magnitude of the arm's endpoint stiffness. To validate our method, we examined how the strength of the power grasp, when holding onto a robotic manipulandum, affected the arm's endpoint stiffness in three different locations of the workspace. The endpoint stiffness magnitude increased linearly with the grasp force, and this linear relationship did not depend on the arm's posture or position in the workspace. The endpoint stiffness may have increased as a combination of greater grasp stiffness and greater arm stiffness, since larger co-contraction was observed in the elbow and shoulder with a stronger grasp. Changes in the grasp force could serve as a metric in assessing how humans adapt their endpoint stiffness magnitude. [ABSTRACT FROM AUTHOR]

Previous studies have shown that rumination has two processing modes: abstract processing mode and concrete processing mode. Abstract processing mode is associated with risk factors for depression. However, the effects of abstract processing mode on the tendency to avoid difficult situations, which is characteristic of major depression, are not clear. Our aim was to elucidate these effects, using laboratory-based methods. Thirty-four university students were recruited and divided into two group conditions abstract processing mode or concrete processing mode rumination. First, participants attempted a mathematics failure task. After the task, participants were interviewed in order to induce each processing mode. After the interview, they attempted the same task and were told that they could stop at any time. Results showed that the abstract processing mode rather than concrete processing mode group showed increased commitment for the second task. This indicated that rumination processing modes may increase the tendency to avoid difficult situations. [ABSTRACT FROM AUTHOR]

Aims: We investigated the changes in insulin requirements, and other relevant factors, in pregnant Japanese women with type 1 diabetes. Methods: This retrospective observational study was conducted on 77 singleton pregnant women with type 1 diabetes, treated with multiple daily injections of insulin. We examined changes in daily insulin dose during pregnancy and defined the increased insulin doses as the ratio of maximum dose to the pre-pregnancy dose. The relationship between the increased insulin doses and maternal features or pregnancy outcomes was investigated. Results: The insulin dose gradually increased during pregnancy, reaching a maximum dose that was 1.6 times of that prior to pregnancy, at 35 weeks of gestation. A negative significant correlation was observed between the insulin dose increases and duration of diabetes (p = 0.008). Greater increases in insulin doses were noted in women with multiparity, compared to nulliparity (p = 0.047). Multiple regression analyses revealed that shorter duration of diabetes was independently associated with the increases in insulin dose during pregnancy. Conclusions: Women with a longer duration of diabetes required smaller increases in insulin dose during pregnancy, suggesting that long diabetic duration may decrease placental function. Further investigations are needed to clarify the mechanisms that the duration of diabetes influences on insulin requirement during pregnancy. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of this study was to analyse the resultant stress induced by joint-line obliquity after HTO for varus knee deformity using a three-dimensional (3D) finite element model analysis.Methods: The geometrical bone data used in this study were derived from commercially available human bone digital anatomy media. The 3D knee models were developed using 3D computer-aided design software. The articular surface was overlaid with a 2-mm-thick cartilage layer for both femoral and tibial condyles. Ligament structures were simulated based on properties reported in previous anatomical studies. Regarding the loading condition, isolated axial loads of 1200 N with lateral joint-line inclinations of 2.5°, 5°, 7.5°, and 10° in reference to the horizontal axis were applied to the femur to simulate the mechanical environment in a knee with joint-line obliquity.Results: A steep rise of shear stress in the medial compartment was noted in the model with obliquity of 5° or more. This laterally directed shear stress exhibited an incremental increase in accordance with the obliquity angle. The maximum shear stress value in the medial cartilage increased from 1.6 MPa for the normal knee to 3.3, 5.2, and 7.2 MPa in the joint-line obliquity models with 5°, 7.5°, and 10° of obliquity, respectively.Conclusions: The effects of HTO for varus knee deformity on the amount/distribution of stresses in the articular cartilage were analysed using a 3D finite element model. It was shown that joint-line obliquity of more than 5° induced excessive shear stress in the tibial articular cartilage. A large amount of correction in OWHTO with a resultant joint-line obliquity of 5° or more may induce detrimental stress to the articular cartilage. Double-level osteotomy should be considered as a surgical option in this situation. [ABSTRACT FROM AUTHOR]

Background: Trastuzumab when combined with fluoropyrimidine and cisplatin was proven to improve survival in patients with human epidermal growth factor receptor 2 (HER2)-positive gastric cancer (GC) in the ToGA study. The safety and efficacy of trastuzumab in combination with docetaxel and S-1 have not yet been evaluated.Methods: This study was a multicenter, phase II study. Patients with chemotherapy-naïve HER2-positive advanced or metastatic GC were eligible. Trastuzumab was administered intravenously on day 1 of the first cycle at 8 and 6 mg/kg in subsequent cycles. Docetaxel was administered intravenously at 40 mg/m2 on day 1 of each cycle. S-1 was administered at a dosage based on body surface area for 14 days in a 3-weekly cycle. The primary endpoint was progression-free survival (PFS).Results: A total of 23 patients were enrolled. Median PFS was 6.7 months (95% CI 4.1-10.1). The response rate (RR) was 39.1%. Median overall survival (OS) and time to treatment failure (TTF) were 17.5 and 4.4 months, respectively. Major grade 3-4 adverse events were neutropenia (39.1%), leukopenia (30.4%), and febrile neutropenia (8.7%).Conclusion: Trastuzumab in combination with docetaxel and S-1 showed effective antitumor activity and manageable toxicities as first-line treatment for patients with HER2-positive GC. [ABSTRACT FROM AUTHOR]