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BACKGROUND: Recovery of walking independence in critically ill patients is required for safe discharge home. However, the pre-admission predictors affecting this outcome in this patient group are unknown. This study aimed to identify these predictors. METHODS: We included subjects who required mechanical ventilation for at least 48 h and could walk before admission. We investigated frailty, cognitive impairment, and malnutrition risk according to the pre-admission health status. Walking independence was defined as the ability to walk for at least 45 m on level ground. The primary outcome was the association between the time to event from an ICU discharge to walking independence, and pre-admission predictors were analyzed using a Fine-Gray proportional hazards regression. RESULTS: The rate of walking independence was 38.0 (100 cases/person-month; sample N = 144). In the proportional hazards regression model, adjusted for covariates, frailty (hazard ratio [HR] 0.08 [95% CI 0.01-0.67]), pre-frailty (HR 0.37 [95% CI 0.14-0.99]), cognitive impairment (HR 0.21 [95% CI 0.05-0.90]), and malnutrition risk (HR 0.20 [95% CI 0.07-0.58]) were associated with walking independence. CONCLUSIONS: Pre-admission frailty or pre-frailty, cognitive impairment, and malnutrition risk can help predict walking independence in critically ill patients who require mechanical ventilation. [ABSTRACT FROM AUTHOR]

Identifying patients who can be spared nonbeneficial surgery is crucial, as pancreatic cancer surgery is highly invasive, with substantial negative effects on quality of life. The study objective was to investigate a useful indicator of patients who do not gain prognostic benefit from radical surgery after neoadjuvant therapy for resectable and borderline resectable pancreatic cancer. We compared factors among 609 patients with resectable or borderline resectable pancreatic cancer receiving neoadjuvant therapy during 2005–2019. Patients were divided into a poor-prognosis group (no surgery or postresection recurrence within a year) and a good-prognosis group (no recurrence or recurrence >1 year after resection). Patients who experience a recurrence within a year of resection (poor-prognosis group) did no better than patients who received neoadjuvant therapy and progressed but never made it to surgery. The value of carbohydrate antigen 19-9 after neoadjuvant therapy was the most significant indicator to predict the poor prognosis group and the elevation of carbohydrate antigen 19-9 (>200 U/mL) identified only poor prognosis group with high specificity of 96.6%. The overall survival of patients with more than 200 of carbohydrate antigen 19-9 after neoadjuvant therapy was significantly very poor and their 2-year survival rate was only 41.4%. A striking elevation of carbohydrate antigen 19-9 after neoadjuvant therapy for resectable or borderline resectable pancreatic cancer is a good indicator of poor prognosis. Patients with carbohydrate antigen 19-9 >200 U/mL after neoadjuvant therapy should not undergo radical surgery. [ABSTRACT FROM AUTHOR]

Background: Predicting the origin of premature ventricular contraction (PVC) from the preoperative electrocardiogram (ECG) is important for catheter ablation therapies. We propose an explainable method that localizes PVC origin based on the semantic segmentation result of a 12‐lead ECG using a deep neural network, considering suitable diagnosis support for clinical application. Methods: The deep learning‐based semantic segmentation model was trained using 265 12‐lead ECG recordings from 84 patients with frequent PVCs. The model classified each ECG sampling time into four categories: background (BG), sinus rhythm (SR), PVC originating from the left ventricular outflow tract (PVC‐L), and PVC originating from the right ventricular outflow tract (PVC‐R). Based on the ECG segmentation results, a rule‐based algorithm classified ECG recordings into three categories: PVC‐L, PVC‐R, as well as Neutral, which is a group for the recordings requiring the physician's careful assessment before separating them into PVC‐L and PVC‐R. The proposed method was evaluated with a public dataset which was used in previous research. Results: The evaluation of the proposed method achieved neutral rate, accuracy, sensitivity, specificity, F1‐score, and area under the curve of 0.098, 0.932, 0.963, 0.882, 0.945, and 0.852 on a private dataset, and 0.284, 0.916, 0.912, 0.930, 0.943, and 0.848 on a public dataset, respectively. These quantitative results indicated that the proposed method outperformed almost all previous studies, although a significant number of recordings resulted in requiring the physician's assessment. Conclusions: The feasibility of explainable localization of premature ventricular contraction was demonstrated using deep learning‐based semantic segmentation of 12‐lead ECG. Clinical trial registration: M26‐148‐8. [ABSTRACT FROM AUTHOR]

Previous studies documented a relative scarcity of remote dynamic triggering of earthquakes in Japan and suggested that it could be related to Japan's predominantly compressive tectonic regime or the more frequent occurrence of large earthquakes in Japan. For example, remote triggering in California, characterized by extensional tectonics, occurs at levels of stress change as small as 0.1 kPa, whereas in Japan, transient stresses =30 kPa are required. However, the dynamic triggering threshold in Japan, following the 2016 Mw 7.0 Kumamoto earthquake, has been found to be of just a few kilopascals, significantly smaller than reported previously. It was proposed that a decrease in the triggering threshold may have taken place in Japan, in particular at volcanic and geothermal areas, after the 2011 Mw 9.0 Tohoku-Oki earthquake. In this study, we analyze the possible change in dynamic triggering conditions in five areas in northeast Japan, where swarm earthquakes have occurred immediately after the Tohoku-Oki earthquake. The triggering thresholds in these five areas have been estimated based on the analysis of waveform recordings of 49 teleseismic earthquakes that occurred between 2004 and 2020. A decrease of the triggering threshold (or triggering ability) is apparent in all but one region. However, a statistical significance Kolmogorov-Smirnov test could not reject, at a 5% level, the null hypothesis stating that "the distribution of dynamic stress changes for triggering earthquakes that occurred before and after the Tohoku-Oki event is the same." We interpret the changes in the triggering threshold to be related to the pore pressure increase (and thus a fault strength decrease) in the crust following the Tohoku-Oki earthquake. Our results also indicate that dynamic triggering in Japan is more common than reported previously. [ABSTRACT FROM AUTHOR]

Background: The Nordic hamstring exercise (NHE) is useful for preventing hamstring strain injuries. However, its adoption rates in the sports field are currently low, necessitating a safe and efficient introduction. Hypothesis/Purpose: The purpose was to examine the relationship between the eccentric force during the NHE and the one repetition maximum of deadlift. It was hypothesized that the eccentric force during the NHE would be correlated with the one repetition maximum (1RM) of the deadlift. Study design: Cross-sectional study. Methods: Healthy student rugby players with no history of hamstring tears were recruited to participate. The peak eccentric forces during the NHE, which is the vertical peak force on the part holding the leg, were measured in both legs, while gradually leaning forward to a prone position over three seconds. The 1RM of deadlift was calculated from the weight that could be raised three times during a deadlift (x kg) using the estimated formula (x kg / 0.93). The correlation between the left and right peak eccentric forces during the NHE, the total left and right forces, and the 1RM of the deadlift was examined using Spearman's rank correlation coefficient, with all values corrected for body mass. Results: During the NHE, the peak eccentric force of the right and left legs and the total peak eccentric force of both legs were 3.8 ± 1.1 N/BM, 3.8 ± 1.2 N/BM, and 7.6 ± 2.1 N/BM, respectively. The 1RM of deadlift was 1.9 ± 0.3 kg/BM. Weak correlations (r = 0.34–0.37) were found between the 1RM of the deadlift and the peak eccentric force in the right and left legs and the total peak eccentric force of both legs. Conclusion: The present study revealed a weak correlation between the peak eccentric force during the NHE and 1RM of deadlift Level of Evidence: 2c [ABSTRACT FROM AUTHOR]

Background Interventions using vibration stimulation have been recognized for their potential for increasing range of motion (ROM) without compromising muscle strength. Handheld vibration massagers can efficiently deliver vibration therapy to the shoulder joint and may be a potential treatment. Purpose To evaluate the effects of vibration massage using a handheld device on the soft tissues of the posterior shoulder joint, particularly on internal rotation (IR) passive ROM and external rotation (ER) muscle strength. Study Design Crossover study design. Methods A crossover study with a 5-min vibration massage and passive control condition was conducted in healthy male volunteers (mean age 20.5 ± 1.7 years). Vibration massage was applied to the posterior shoulder soft tissues of the dominant arm, with no intervention under control conditions. IR-ROM (vertebral level and in abduction) and strength of the external rotators (isometric and isokinetic) were measured before and immediately after the intervention. Vertebral levels were calculated as a ratio of lengths (ratio decreases with increased mobility). IR-ROM in abduction, the angle was measured. Statistical analysis was performed with two-way repeated measures ANOVA and paired t-test (Bonferroni correction). Results Vibration application decreased (improved) vertebral level IR ROM by -4.1% (p < 0.01, d = 0.445) and increased abduction position IR ROM by 11.4° (p < 0.01, d = 0.694). These changes exceeded the 95% confidence interval for the minimum detectable change. By contrast, the control condition produced no changes. IR-ROM (vertebral level and abduction) immediately after the intervention showed significant differences between the control and vibration conditions (p = 0.036, d = 0.273; p = 0.048, d = 0.483, respectively). Muscle strength did not show any interaction, time, or between-condition effects. Conclusions A massage using a handheld vibration massager applied to the posterior shoulder soft tissues increased IR-ROM without negatively affecting muscle strength, suggesting its potential use as a means of warming up. Level of Evidence Level 3 [ABSTRACT FROM AUTHOR]

• Older people with frailty are at high risk of developing pneumonia. • Pneumonia is associated with decreased cough strength. • Cough strength is related to inspiratory muscle strength. • Inspiratory muscle training improves cough strength in older people with frailty. • Inspiratory muscle training could prevent pneumonia in older people. To investigate the effect of inspiratory muscle training (IMT) on cough strength in older people with frailty. Single-blind randomized controlled trial. Day health care centers at 2 sites. Older people with frailty (N=60). Eligible people were randomly assigned to receive IMT program in addition to general exercise training (IMT group), or general exercise training alone (control group). The IMT group performed training using a threshold IMT device with the load set at 30% of maximum inspiratory mouth pressure in addition to the general exercise training program throughout the 8 weeks. The IMT took place twice a day and each session consisted of 30 breaths. Primary outcome was cough strength, measured as the cough peak flow (CPF), at the beginning and the end of the program. Data from 52 participants (26 in each group) were available for the analysis. The mean age was 82.6 years; 33% were men. The change in CPF at the end of the program was 28.7±44.4 L/min in the IMT group and −7.4±26.6 L/min in the control group. A linear regression model showed that the presence or absence of IMT was associated with changes in CPF (mean difference between groups, 36.3; 95% confidence interval, 16.7-55.9; effect size, 0.99). IMT may be a useful intervention to improve cough strength in frail older people. [Display omitted] [ABSTRACT FROM AUTHOR]

Temporomandibular joint (TMJ) disc displacement without reduction, often referred to as closed lock, is a debilitating condition characterized by a sudden decrease in mouth opening capacity, accompanied by TMJ pain. Over time, this closed lock can lead to the development of TMJ osteoarthritis (OA). While conservative treatments effectively alleviate TMJ pain and improve jaw function in most patients, they seldom restore normal TMJ structures. In this case report, we present a rare case of a 39-year-old woman who experienced the restoration of a normal disc-condyle-mandibular fossa relationship and the repair of OA changes following self-care for chronic TMJ closed lock with OA. She initially presented with a 7-month history of left TMJ pain and limited mouth opening persisting. Magnetic resonance imaging (MRI) of the left TMJ showed anterior disc displacement without reduction and OA changes including erosion, subchondral cyst, and sclerosis of the subchondral bone in the left condyle. Self-care, including parafunction control and stretching exercises, relieved the TMJ pain and increased the range of mouth opening. A follow-up MRI obtained 13 months following the initial MRI revealed a normal disc-condyle-mandibular fossa relationship and repair of the surface erosion with the subchondral cyst. Our clinical findings indicate that although rare, restoration of the normal disc-condyle-mandibular fossa relationship and condylar repair are possible through self-care for chronic closed lock with OA. [ABSTRACT FROM AUTHOR]

In the decommissioning of the Fukushima Daiichi Nuclear Power Station, understanding the distribution of radioactive substances and dose-equivalent rates is crucial to develop detailed decontamination plans and minimize worker exposure. In this study, we remotely visualized radioactive hotspots and dose-equivalent rate distribution in Unit 1 reactor building of the station using a Mecanum wheel robot equipped with a Compton camera, simultaneous localization and mapping device, and survey meter. We successfully visualized high-concentration radioactive hotspots on the U-shaped piping of the drywell humidity control system and the atmospheric control piping in the ceiling in front of the transverse in-core probe room. Furthermore, the hotspot location was identified in three dimensions using the Compton camera used to analyze the atmospheric control piping. By simultaneously analyzing the dose-equivalent rate data acquired by the survey meter and the hotspot locations visualized by the Compton camera, it was confirmed that the hotspots caused elevated dose-equivalent rates in the surrounding area. In the future, if this robotic system is used in unexplored areas, such as the upper floors of reactor buildings, it can provide information about the locations of radioactive hotspots and the distribution of dose-equivalent rates. [ABSTRACT FROM AUTHOR]

Background: The Medical Information Database Network (MID-NET®) in Japan is a vast repository providing an essential pharmacovigilance tool. Gastrointestinal perforation (GIP) is a critical adverse drug event, yet no well-established GIP identification algorithm exists in MID-NET®. Methods: This study evaluated 12 identification algorithms by combining ICD-10 codes with GIP therapeutic procedures. Two sites contributed 200 inpatients with GIP-suggestive ICD-10 codes (100 inpatients each), while a third site contributed 165 inpatients with GIP-suggestive ICD-10 codes and antimicrobial prescriptions. The positive predictive values (PPVs) of the algorithms were determined, and the relative sensitivity (rSn) among the 165 inpatients at the third institution was evaluated. Results: A trade-off between PPV and rSn was observed. For instance, ICD-10 code-based definitions yielded PPVs of 59.5%, whereas ICD-10 codes with CT scan and antimicrobial information gave PPVs of 56.0% and an rSn of 97.0%, and ICD-10 codes with CT scan and antimicrobial information as well as three types of operation codes produced PPVs of 84.2% and an rSn of 24.2%. The same algorithms produced statistically significant differences in PPVs among the three institutions. Combining diagnostic and procedure codes improved the PPVs. The algorithm combining ICD-10 codes with CT scan and antimicrobial information and 80 different operation codes offered the optimal balance (PPV: 61.6%, rSn: 92.4%). Conclusion: This study developed valuable GIP identification algorithms for MID-NET®, revealing the trade-offs between accuracy and sensitivity. The algorithm with the most reasonable balance was determined. These findings enhance pharmacovigilance efforts and facilitate further research to optimize adverse event detection algorithms. [ABSTRACT FROM AUTHOR]

Immune checkpoint inhibitors (ICIs) have been clinically used to treat various cancers. This has resulted in a paradigm shift in the treatment of cancers, including recurrent/metastatic oral squamous cell carcinoma (R/M OSCC); however, response rate to treatment with ICIs is limited to 20–30%, and the treatment efficacy varies among patients. Therefore, developing a stratification method to accurately select patients expected to respond to the treatment would be beneficial. Extracellular vesicles (EVs) are important mediators of intercellular communication. Notably, programmed death-ligand 1 (PD-L1) is expressed on the surface of EVs in several malignancies. Herein, we focused on the clinical significance of PD-L1-expressing EVs (PD-L1 EVs) circulating in the serum of patients with R/M OSCC treated with ICIs. Overall, 37 patients with R/M OSCC who were treated with ICIs at our institution were evaluated, and the optimum cutoff level of PD-L1 EVs was determined using a receiver operating characteristic analysis. Furthermore, we evaluated the association between PD-L1 EV levels and various clinicopathological features as well as the effects of PD-L1 EVs status on prognosis. The optimum cutoff level of PD-L1 EVs was 2.90 ng/mL. Further, Kaplan–Meier curve analysis revealed that high PD-L1 EV level was significantly associated with poor overall survival. Moreover, multivariate analysis indicated that high PD-L1 EV level was independently correlated with poor 5-year overall survival. These findings indicate that assessing levels of PD-L1 EVs in serum before treatment may be a valuable prognostic indicator for patients with R/M OSCC following ICIs treatment. [ABSTRACT FROM AUTHOR]

This systematic review and meta-analysis aimed to compare the effectiveness of selective neck dissection (SND) and comprehensive neck dissection (CND) in patients with oral squamous cell carcinoma N1 (Level I). Randomized controlled trials and prospective and retrospective non-randomized clinical studies were selected and evaluated for the certainty of evidence using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach. The statistical analysis was performed using Review Manager 5.4 software. We included one observational study. The analysis revealed no difference in survival rates (overall survival, disease-specific survival, and regional control) between SND and CND for oral squamous cell carcinoma N1 (level I) cases. In the included study, the risk of bias was high, total sample size was small, and certainty of evidence was rated as "very low.". This systematic review and analysis suggested no difference in effectiveness between SND and CND; however, a high certainty of evidence could not be determined. Such evidence needs to be established through future systematic reviews, including randomized controlled trials with larger sample sizes. [ABSTRACT FROM AUTHOR]

The Japan Atomic Energy Agency has been developing 9Cr-oxide dispersion strengthened (ODS) steel as a fuel cladding material for sodium-cooled fast reactors (SFRs). Previous studies have formulated the creep rupture equation for 650°C–850°C. However, little data have been obtained above 850°C, and no equation has been formulated. This study conducted creep tests to evaluate creep strength at 700°C–1000°C. Two creep test methods, the internal pressure and ring creep tests under development, were used, and the validation of the ring creep test method was conducted. The results showed that 9Cr-ODS steel undergoes almost no strength change due to the matrix's phase transformation, and a single equation can express a creep rupture strength from 700°C to 1000°C. In validating the ring creep test method, analysis clarified the effect of stress concentration on the specimen. Plastic deformation occurs at high initial stress and may lead to early rupture. The results will be essential for future creep testing and evaluation of neutron-irradiated 9Cr-ODS steel. [ABSTRACT FROM AUTHOR]

Hepatocellular carcinoma, historically, has had a poor prognosis with very few systemic options. Furthermore, most patients at diagnosis are not surgical candidates. Therefore, locoregional therapy (LRT) has been widely used, with strong data supporting its use. Over the last 15 years, there has been progress in the available systemic agents. This has led to the updated Barcelona Clinic Liver Cancer (BCLC) algorithm's inclusion of these new systemic agents, with advocacy of earlier usage in those who progress on LRT or have tumor characteristics that make them less likely to benefit from LRT. However, neither the adjunct of LRT nor the specific sequencing of combination therapies is addressed directly. This Research Consensus Panel sought to highlight research priorities pertaining to the combination and optimal sequencing of LRT and systemic therapy, assessing the greatest needs across BCLC stages. [Display omitted] [ABSTRACT FROM AUTHOR]

[Display omitted] • Outpatient cardiac rehabilitation (CR) is a promising tool to stroke survivors. • Outpatient CR improved motor function, but not emotional health after 3-month CR. • Some emotional health concerns may associate with outpatient CR to stroke survivors. Outpatient cardiac rehabilitation (CR) is a promising tool for improving functional outcome in stroke survivors, however, evidence for improving emotional health is limited. We aimed to clarify the effects of outpatient CR following in-hospital stroke rehabilitation on health-related quality of life (HRQOL) and motor function. Patients with acute ischemic stroke or transient ischemic attack discharged directly home were recruited, and 128 patients who fulfilled criteria for insurance coverage of CR were divided into the CR (+) group (n = 46) and CR (-) group (n = 82). All patients underwent in-hospital stroke rehabilitation, and within 2 months after stroke onset, patients in the CR (+) group started a 3-month outpatient CR program of supervised sessions. Changes of motor function and HRQOL assessed by the short form-36 version 2 (SF-36) from discharge to 3 months post-discharge were compared between the two groups. Twenty-six patients in the CR (+) group completed the program and 66 patients in the CR (-) group were followed up at a 3-month examination. Least-square mean changes in 6-minute walk distance and isometric knee extension muscle strength were significantly higher in the CR (+) group than the CR (-) group (52.6 vs. 16.3 m; 10.1 vs. 3.50 kgf/kg). Improvement of HRQOL at 3 months was not observed in the CR (+) group. Outpatient CR following in-hospital stroke rehabilitation within 2 months after stroke onset improved exercise tolerance and functional strength but not HRQOL assessed by the SF-36 after completion of CR in the present cohort. [ABSTRACT FROM AUTHOR]

This study evaluated the effectiveness of intra-arterial infusion chemoradiotherapy (IACRT) compared to surgery in patients with locally advanced oral squamous cell carcinoma (LAOSCC) as part of the process of updating the 2019 Japanese oral cancer clinical practice guidelines. We searched PubMed, Japana Centra Revuo Medicina Web, and the Cochrane Central Register of Controlled Trials (from 2019 to 2022) to identify articles that evaluated the effectiveness of IACRT and surgery in patients with LAOSCC. Because no randomized controlled trials were identified, we searched observational studies, such as cohort studies and case-control studies. A total of 337 articles were identified, and two studies were selected through the search. The only primary endpoint that was assessed was the locoregional recurrence rate. The hazard ratio for the locoregional recurrence rate was 1.03, with a 95 % confidence interval of 0.77–2.18, and the point estimate was slightly in favor of the control group. However, there were large discrepancies between the proportions of early-stage OSCC and LAOSCC in the two articles. The balance between the desirable and undesirable effects of the intervention was not known. The certainty of evidence was very low. In this systematic review, the evidence of a desirable effect was small, and the balance between effectiveness and harms was not known. Some Japanese hospitals have reported good outcomes with IACRT for patients with LAOSCC. We must therefore exercise caution in analyzing this result. [ABSTRACT FROM AUTHOR]

A few reports have demonstrated the additional survival benefit obtained from induction chemotherapy. However, some facilities have differing opinions regarding the suitability of induction chemotherapy. The aim of this systematic review was to investigate the effectiveness of induction chemotherapy in patients with unresectable oral cancers without distant metastases. A comprehensive search of randomized controlled trials was conducted specifically targeting patients with primary unresectable oral cancer, defined as an intervention group (induction chemotherapy followed by chemoradiotherapy) and a control group (chemoradiotherapy alone). The electronic databases PubMed, Cochrane Central Register of Controlled Trials, and Ichushi-Web database were searched for relevant papers. The primary outcome was overall survival, and the secondary outcomes were progression-free survival and treatment-related deaths, all of which were judged to be of critical importance. Data available for integration were subjected to a meta-analysis, and the certainty of evidence was assessed with the Grading of Recommendations Assessment, Development, and Evaluation approach. A search was conducted until February 2022, and four articles were included. The meta-analysis showed that the point estimates (95 % confidence interval) of the hazard ratios were 0.87 (0.74–1.01) for overall survival, 0.85 (0.75–0.97) for progression-free survival, and 0.98 (0.97–1.00) for treatment-related death. The certainty of the evidence for each item was very low. Little data are available to support the use of induction chemotherapy before chemoradiotherapy in patients with unresectable primary locally advanced oral cancer. [ABSTRACT FROM AUTHOR]

This systematic review (SR) and meta-analysis aimed to evaluate the outcomes of radiotherapy (RT) alone and chemoradiotherapy (CRT) in patients with primary unresectable locally advanced oral cancer without distant metastases. Searches were performed on PubMed, Cochrane Central Register of Controlled Trials (CENTRAL), and Ichushi-Web databases for articles published from inception until March 31, 2022. We selected clinical practice guidelines, SRs, and randomized controlled trials (RCTs) according to pre-established criteria. Prospective and retrospective observational clinical studies, case reports, and case series were included unless appropriate SRs or RCTs were not available. Outcomes were overall survival (OS), progression-free survival (PFS), and severe oral mucositis. We used Review Manager 5.4 software for statistical analysis and rated the certainty of the evidence using the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) approach. Two RCTs, with a total of 400 patients who received RT alone (205 patients) and CRT (195 patients), were eligible. The meta-analysis shows that CRT was favorably associated with OS compared with RT alone, and the certainty of the evidence was moderate. Additionally, CRT was also associated with favorable PFS compared to RT alone, and the certainty of evidence was low. Regarding side effects, CRT was associated with a higher incidence of grade ≥ 3 mucositis than RT alone, and the certainty of evidence was low. CRT was favorably associated with OS and PFS compared to RT alone in patients with primary unresectable locally advanced oral cancer without distant metastasis; however, the incidence of oral mucositis increased. [ABSTRACT FROM AUTHOR]

This systematic review and meta-analysis aimed to examine whether neoadjuvant chemotherapy (NAC) is useful against resectable oral squamous cell carcinomas. Three reviewers searched PubMed, Cochrane CENTRAL, and Ichushi-Web to identify clinical practice guidelines, systematic reviews (SRs), randomized controlled trials (RCTs), and prospective and retrospective non-randomized clinical (observational) studies according to pre-established eligibility and exclusion criteria. We systematically reviewed these selected articles and performed a meta-analysis of overall survival, disease-free survival, local recurrence, and distant metastasis. We used Review Manager 5.4 software for statistical analysis and rated the certainty of the evidence using the GRADE approach. Six RCTs (three studies) were eligible. The regimens involved were either PF (cisplatin+5-fluorouracil, 3 weekly, 3 cycles) or TPF (docetaxel+cisplatin+5-fluorouracil, 3 weekly, 2 cycles). The number of patients in the three studies were 198 (NAC-PF and Control group: 99 each), 256 (NAC-TPF and Control group: 128 each), and 68 (NAC-TPF and Control group: 34 each), respectively. The meta-analysis showed no difference between intervention and control groups in any of the outcomes of overall survival, disease-free survival, local recurrence, or distant metastases, and was considered at serious risk of bias, therefore the certainty of the evidence was 'very low' for all outcomes. NAC with multiple cytotoxic anticancer agents (PF/TPF) has very low efficacy and certainty of evidence for patients with resectable oral squamous cell carcinoma. Considering the risk of adverse events, we propose not performing NAC-PF/TPF. [ABSTRACT FROM AUTHOR]

The myotendinous junction (MTJ) is a vulnerable region at the interface of skeletal muscle and tendon that forms an integrated mechanical unit. This study presents a technique for the spatially restrictive co-culture of human embryonic stem cell (hESC)-derived skeletal myocytes and primary tenocytes for two-dimensional modeling of the MTJ. Micropatterned lanes of extracellular matrix and a 2-well culture chamber define the initial regions of occupation. On day 1, both lines occupy less than 20 % of the initially vacant interstitial zone, referred to henceforth as the junction. Myocyte–tenocyte interdigitations are observed by day 7. Immunocytochemistry reveals enhanced organization and alignment of patterned myocyte and tenocyte features, as well as differential expression of multiple MTJ markers. On day 24, electrically stimulated junction myocytes demonstrate negative contractile strains, while positive tensile strains are exhibited by mechanically passive tenocytes at the junction. Unpatterned tenocytes distal to the junction experience significantly decreased strains in comparison to cells at the interface. Unpatterned myocytes have impaired organization and uncoordinated contractile behavior. These findings suggest that this platform is capable of inducing myocyte–tenocyte junction formation and mechanical coupling similar to the native MTJ, showing transduction of force across the cell–cell interface. The myotendinous junction (MTJ) is an integrated structure that transduces force across the muscle-tendon boundary, making the region vulnerable to strain injury. Despite the clinical relevance, previous in vitro models of the MTJ lack the structure and mechanical accuracy of the native tissue and have difficulty transmitting force across the cell–cell interface. This study demonstrates an in vitro model of the MTJ, using spatially restrictive cues to inform human myocyte–tenocyte interactions and architecture. The model expressed MTJ markers and developed anisotropic myocyte–tenocyte integrations that resemble the native tissue and allow for force transduction from contracting myocytes to passive tenocyte regions. As such, this study presents a system capable of investigating development, injury, and pathology in the human MTJ. [Display omitted] [ABSTRACT FROM AUTHOR]