The effectiveness of a self-reported questionnaire on masticatory function in health examinations.

Periodontal diseases have been reported to be lifestyle-related and associated with metabolic syndrome (MetS). The introduction of dental checkups in a health checkup program may create a synergistic effect and aid the prevention of MetS. In Japan, a chewing function questionnaire has now been introduced into the national health checkup program. The purpose of this study was to investigate whether the questionnaire reflects dental and oral conditions and whether it helps improve general and oral health. A total of 6599 subjects who underwent health checkups or guidance specified by the National Health Insurance of Japan for two consecutive years were included. A single comprehensive question to evaluate masticatory function was asked. Medical and dental examinations and insurance data were collected and used for analysis. In terms of masticatory function during chewing, 82.3% of subjects experienced no problems, 17.3% experienced some difficulty, and 0.4% experienced severe problems. There was a significant relationship between the questionnaire response and dental examinations results for several items of examination. The overall dental consultation rate after health screening was 42.3%. Improvement in periodontal disease was achieved in those who reported some problems with chewing function. Improvement in blood pressure was also observed in those who reported some problem with chewing function and subsequently had a dental consultation. The results of this study indicate that questionnaires on masticatory function reflect the status of dental and oral health. In addition, the results suggested that questionnaire results are potentially linked to improvement in dental and oral health status, and improvement in MetS.

The lymphocyte/monocyte ratio predicts the efficacy of isatuximab plus pomalidomide in multiple myeloma patients.

BACKGROUND: Isatuximab, an anti-CD38 antibody, has been widely used in treatments for patients with relapsed/refractory multiple myeloma (MM). Despite its high efficacy, not all patients achieve a lasting therapeutic response with isatuximab. OBJECTIVE: We tried to identify biomarkers to predict the effectiveness of isatuximab by focusing on the host's immune status before treatment. METHODS: We retrospectively analyzed the cases of 134 relapsed/refractory MM patients in the Kansai Myeloma Forum database who had received only a first isatuximab treatment. RESULTS: Among the 134 patients, an isatuximab, pomalidomide and dexamethasone (Isa-PD) regimen, isatuximab, carfilzomib and dexamethasone (Isa-KD) regimen and isatuximab and/or dexamethasone (Isa-D) regimen were used in 112, 15 and 7 patients, respectively. The median age at treatment, number of prior treatment regimens, and progression-free survival (PFS) were 71, 6, and 6.54 months, respectively. Multivariate analysis showed that the PFS under the Isa-PD regimen was longer in patients with higher lymphocyte/monocyte ratio (LMR ≥ 4), fewer prior treatment regimens (< 6), and no use of prior daratumumab treatment. The OS under the Isa-PD regimen was longer in patients with higher white blood cell counts (WBC counts ≥ 3000/µL) and higher LMR. The PFS under the Isa-D regimen was longer in patients with fewer prior treatment regimens in univariate analysis, but no parameters were correlated with PFS/OS under the Isa-KD regimen. CONCLUSION: We found that the patients with higher LMR (≥ 4) could obtain longer PFS and OS under the Isa-PD regimen. Other cohort studies of isatuximab treatment might be necessary to substantiate our results.

Consensus Paper: Cerebellum and Reward.

Cerebellum is a key-structure for the modulation of motor, cognitive, social and affective functions, contributing to automatic behaviours through interactions with the cerebral cortex, basal ganglia and spinal cord. The predictive mechanisms used by the cerebellum cover not only sensorimotor functions but also reward-related tasks. Cerebellar circuits appear to encode temporal difference error and reward prediction error. From a chemical standpoint, cerebellar catecholamines modulate the rate of cerebellar-based cognitive learning, and mediate cerebellar contributions during complex behaviours. Reward processing and its associated emotions are tuned by the cerebellum which operates as a controller of adaptive homeostatic processes based on interoceptive and exteroceptive inputs. Lobules VI-VII/areas of the vermis are candidate regions for the cortico-subcortical signaling pathways associated with loss aversion and reward sensitivity, together with other nodes of the limbic circuitry. There is growing evidence that the cerebellum works as a hub of regional dysconnectivity across all mood states and that mental disorders involve the cerebellar circuitry, including mood and addiction disorders, and impaired eating behaviors where the cerebellum might be involved in longer time scales of prediction as compared to motor operations. Cerebellar patients exhibit aberrant social behaviour, showing aberrant impulsivity/compulsivity. The cerebellum is a master-piece of reward mechanisms, together with the striatum, ventral tegmental area (VTA) and prefrontal cortex (PFC). Critically, studies on reward processing reinforce our view that a fundamental role of the cerebellum is to construct internal models, perform predictions on the impact of future behaviour and compare what is predicted and what actually occurs.

Dental and oral management in the perioperative period of surgery: A scoping review.

Dental and oral management (DOM) is a long-established treatment modality. This scoping review aimed to narratively review previous studies, examine the effects of perioperative DOM, and identify the available evidence. A literature search was conducted using the PubMed electronic database for studies published between January 1, 2000, and March 8, 2022. The search yielded 43 studies, most of which were published in the last 10 years. The results of this study confirmed that improved perioperative oral hygiene is effective in preventing postoperative pneumonia. Our results also suggested that preoperative DOM is effective in preventing postoperative surgical site infections. Perioperative DOM is effective in reducing the incidence of postoperative pneumonia, SSI, and postsurgical complications. Further studies are needed to elucidate the various mechanism of DOM and to examine efficient intervention methods and timing.

Japanese survey of perioperative complications and ureteral stricture after ureteroscopy with laser lithotripsy for upper urinary tract stones in multicenter collaborative study.

OBJECTIVES: This study aimed to investigate perioperative complications and the details of postoperative ureteral stricture after ureteroscopy with laser lithotripsy (URS-L) for upper urinary tract stones in Japan. METHODS: Patient data on intra- and postoperative complications after ureteroscopy using URS-L were retrospectively collected from multiple centers in Japan between April 2017 and March 2020 with the cooperation of the Japanese Society of Endourology and Robotics. Data included the number of patients undergoing URS-L, number and type of intra- and postoperative complications, and detailed characteristics of postoperative ureteral stricture. RESULTS: In total, 14 125 patients underwent URS-L over 3 years at 82 institutions. Annual URS-L numbers gradually increased from 4419 in 2017, to 4760 in 2018, and 4946 in 2019. The total complication rate was 10.5%, which was divided into intra-operative complications in 1.40% and postoperative complications in 9.18%. The annual incidences of intra- and postoperative complications were not significantly different from year to year (p = 0.314 and p = 0.112). Ureteral perforation, ureteral avulsion, and the intra-operative conversion rate were 1.35%, 0.03%, and 0.02%, respectively. Fever >38°C, septic shock, blood transfusion, and postoperative mortality were 7.44%, 0.81%, 0.07%, and 0.04%, respectively. Ureteral stricture occurred in 0.8% of cases. The median length of stricture site was 10.0 mm and the success rate of stricture treatment was 54.6%. CONCLUSION: Although URS-L utilization has increased in Japan, the annual complication rate has remained steady. Although URS-L is a useful and less invasive procedure, devastating complications can still occur.

Depletion of Ppp6c in hematopoietic and vascular endothelial cells causes embryonic lethality and decreased hematopoietic potential.

Protein phosphatase 6 (PP6) is a serine/threonine (Ser/Thr) protein phosphatase, and its catalytic subunit is Ppp6c. PP6 forms the PP2A subfamily with PP2A and PP4. The diverse phenotypes observed following small interfering RNA (siRNA)-based knockdown of Ppp6c in cultured mammalian cells suggest that PP6 plays roles in cell growth and DNA repair. There is also evidence that PP6 regulates nuclear factor kappa B (NF-κB) signaling and mitogen-activated protein kinases and inactivates transforming growth factor-ß-activated kinase 1 (TAK1). Loss of Ppp6c causes several abnormalities, including those of T cell and regulatory T cell function, neurogenesis, oogenesis, and spermatogenesis. PP2A has been reported to play an important role in erythropoiesis. However, the roles of PP6 in other hematopoietic cells have not been investigated. We generated Ppp6cfl/fl;Tie2-Cre (Ppp6cTKO) mice, in which Ppp6c was specifically deleted in hematopoietic and vascular endothelial cells. Ppp6cTKO mice displayed embryonic lethality. Ppp6c deficiency increased the number of dead cells and decreased the percentages of erythroid and monocytic cells during fetal hematopoiesis. By contrast, the number of Lin-Sca-1+c-Kit+ cells, which give rise to all hematopoietic cells, was slightly increased, but their colony-forming cell activity was markedly decreased. Ppp6c deficiency also increased phosphorylation of extracellular signal-regulated kinase 1/2 and c-Jun amino (N)-terminal kinase in fetal liver hematopoietic cells.

Efficacy of elotuzumab for multiple myeloma deteriorates after daratumumab: a multicenter retrospective study.

Elotuzumab-based regimens are sometimes selected for multiple myeloma treatment after daratumumab-based regimens. However, there has been insufficient discussion on the efficacy of elotuzumab after daratumumab. We used Kansai Myeloma Forum registration data in a multicenter retrospective evaluation of the efficacy of elotuzumab after daratumumab. Overall survival (OS) rate and time to next treatment (TTNT) were significantly worse in the cohort given elotuzumab after daratumumab (Dara cohort, n = 47) than in the cohort with no history of daratumumab administration before elotuzumab (No-Dara cohort, n = 80, OS: P = 0.03; TTNT: P = 0.02; best response: P < 0.01). In the Dara cohort, OS and TTNT rates were worse with sequential elotuzumab use after daratumumab than with non-sequential (OS: P = 0.02; TTNT: P = 0.03). In patients given elotuzumab < 180 days after daratumumab, OS (P = 0.08) and best response (P = 0.21) tended to be worse, and TTNT was significantly worse (P = 0.01), than in those given elotuzumab after ≥ 180 days. These findings were confirmed by subgroup analyses and multivariate analyses. Monoclonal-antibody-free treatment might be preferable after daratumumab-based regimens. If possible, elotuzumab-based regimens should be considered only ≥ 180 days after daratumumab use.

[The Successful Reduction of Resected Lung Volume for Intralobar Pulmonary Sequestration with Infrared Thoracoscope].

A 59-year-old male patient was referred to our hospital for further examinations and treatment due to an abnormal shadow detected in his left lower lung lobe on computed tomography. The patient was diagnosed with intralobar pulmonary sequestration and scheduled for an operation. During the surgery, after resection of the aberrant artery, indocyanine green was intravenously injected, and the border between normal lung and sequestrated lung was clearly identified by an infrared thoracoscope. Subsequently, wedge resection was performed, and the patient was discharged on postoperative day 5. Spirometry performed 6 months after the surgery indicated that the patient's lung function was well-preserved compared to the preoperative status.

Educational inequalities in all-cause and cause-specific mortality in Japan: national census-linked mortality data for 2010-15.

BACKGROUND: Due to the lack of a national mortality inequality monitoring framework, the overall picture in Japan remains unclear. Here, we investigated educational inequalities in mortality and their cause-specific contribution in Japan. METHOD: Data were obtained by linking the 2010 Japanese population census and death records between 1 October 2010 and 30 September 2015. We included 7 984 451 Japanese people aged 30-79 years who had a unique 'matching key' generated by sex, birth year/month, address (municipality), marital status and age of spouse (9.9% of the total census population). We computed population-weighted all-cause and cause-specific age-standardized mortality rates (ASMRs) by education level. In addition, we calculated the slope index of inequality (SII), relative index inequality (RII) by education level, and population attributable fraction (PAF) referenced with the highest education (e.g. university graduation). RESULTS: Individuals with less education had higher all-cause and cause-specific ASMRs than highly educated individuals. All-cause SII (per 100 000 person-years) values were 433 (95% CI: 410-457) for men and 235 (95% CI: 217-252) for women. RII values were 1.48 (95% CI: 1.45-1.51) for men and 1.47 (95% CI: 1.43-1.51) for women. Estimated PAFs, excess premature deaths caused by educational inequalities, were 11.6% for men and 16.3% for women, respectively. Cerebrovascular diseases, ischaemic heart diseases and lung cancer were the major contributors to mortality inequalities for both sexes. CONCLUSIONS: This first census-based comprehensive report on cause-specific educational mortality inequalities suggested that differences in unfavourable health risk factors by educational background might be associated with these inequalities in Japan.

(R)-ketamine restores anterior insular cortex activity and cognitive deficits in social isolation-reared mice.

Chronic social isolation increases the risk of mental health problems, including cognitive impairments and depression. While subanesthetic ketamine is considered effective for cognitive impairments in patients with depression, the neural mechanisms underlying its effects are not well understood. Here we identified unique activation of the anterior insular cortex (aIC) as a characteristic feature in brain-wide regions of mice reared in social isolation and treated with (R)-ketamine, a ketamine enantiomer. Using fiber photometry recording on freely moving mice, we found that social isolation attenuates aIC neuronal activation upon social contact and that (R)-ketamine, but not (S)-ketamine, is able to counteracts this reduction. (R)-ketamine facilitated social cognition in social isolation-reared mice during the social memory test. aIC inactivation offset the effect of (R)-ketamine on social memory. Our results suggest that (R)-ketamine has promising potential as an effective intervention for social cognitive deficits by restoring aIC function.

Proposal of the novel predictive model for postoperative pancreatic fistula in distal pancreatectomy for pancreatic tumor based on preoperative imaging parameters and stapler handling.

BACKGROUND: Distal pancreatectomy (DP) using linear staplers is widely performed; however, postoperative pancreatic fistulas (POPF) remain an issue. This study aimed to analyze preoperative risk factors for POPF and assess stapler handling. METHODS: We retrospectively analyzed consecutive patients who underwent DP for pancreatic tumors using a linear stapler between 2014 and 2022. Preoperative measurements included pancreas-to-muscle signal intensity ratio (SIR) on fat-suppressed T1-weighted magnetic resonance imaging (MRI). The main outcome was clinically relevant POPF of the 2016 International Study Group of Pancreatic Fistulas definition. The predictive ability of the model was compared with the distal fistula risk score (D-FRS) by using the area under the receiver operating characteristic curve (AUROC). RESULTS: Among the 81 patients, POPF occurred in 31 (38.2%). Multivariate analysis identified computed tomography-measured pancreatic thickness (odds ratio [OR] 1.30, 95% confidence interval [CI] 1.05-1.61, p = 0.009) and SIR on T1-weighted MRI (OR 6.85, 95% CI 1.71-27.4, p = 0.002) as preoperative predictors. A novel preoperative model, "Thickness × MRI (TM)"-index, was established by multiplying these two variables. The TM-index exhibited the highest predictability preoperatively (AUROC 0.757, 95% CI 0.649-0.867). In the intraoperative variable analyses, TM-index (p < 0.001), thin cartridge application (p = 0.032), and short pre-firing compression (p = 0.047) were identified as significant risk factors for POPF. The model's AUROC combined with these two stapler handling methods was higher than D-FRS (0.851 vs. 0.660, p = 0.006). CONCLUSIONS: The novel preoperative model exhibited excellent predictability. Thick cartridge use and long pre-firing compression were protective factors against POPF. This model may facilitate preventive surgical strategy development to reduce POPF.

Impact of cytogenetic abnormalities in symptomatic multiple myeloma; a Japanese real-world analysis from Kansai Myeloma Forum.

To evaluate the specific prognostic value of CAs, we conducted an analysis of 923 symptomatic multiple myeloma patients. Among this cohort, 480 patients had complete data set of high-risk CAs by interphase fluorescent in situ hybridization at diagnosis. In the high-risk group analysis, the median OS of patients without CAs (n = 338, 72 %) was 6.5 years, patients with del(17p) (n = 42, 9 %) was 4.4 years, patients with t(4;14) or t(14;16) (n = 72, 15 %) was 4.4 years, and patients with double-positive CAs(del(17p) and t(4;14) or t(14;16)) (n = 18, 4 %) was 2.1 years (p = 0.032). Patients with double-positive CAs had a significantly worse prognosis.

Morphological and Functional Principles Governing the Plasticity Reserve in the Cerebellum: The Cortico-Deep Cerebellar Nuclei Loop Model.

Cerebellar reserve compensates for and restores functions lost through cerebellar damage. This is a fundamental property of cerebellar circuitry. Clinical studies suggest (1) the involvement of synaptic plasticity in the cerebellar cortex for functional compensation and restoration, and (2) that the integrity of the cerebellar reserve requires the survival and functioning of cerebellar nuclei. On the other hand, recent physiological studies have shown that the internal forward model, embedded within the cerebellum, controls motor accuracy in a predictive fashion, and that maintaining predictive control to achieve accurate motion ultimately promotes learning and compensatory processes. Furthermore, within the proposed framework of the Kalman filter, the current status is transformed into a predictive state in the cerebellar cortex (prediction step), whereas the predictive state and sensory feedback from the periphery are integrated into a filtered state at the cerebellar nuclei (filtering step). Based on the abovementioned clinical and physiological studies, we propose that the cerebellar reserve consists of two elementary mechanisms which are critical for cerebellar functions: the first is involved in updating predictions in the residual or affected cerebellar cortex, while the second acts by adjusting its updated forecasts with the current status in the cerebellar nuclei. Cerebellar cortical lesions would impair predictive behavior, whereas cerebellar nuclear lesions would impact on adjustments of neuronal commands. We postulate that the multiple forms of distributed plasticity at the cerebellar cortex and cerebellar nuclei are the neuronal events which allow the cerebellar reserve to operate in vivo. This cortico-deep cerebellar nuclei loop model attributes two complementary functions as the underpinnings behind cerebellar reserve.

Management of Patients Receiving Antiplatelet Therapy During Gastroenterological Surgery: A Multicenter Prospective Cohort Study (GSATT).

OBJECTIVE: This study aimed to evaluate the effect of continuing preoperative aspirin monotherapy on surgical outcomes in patients receiving antiplatelet therapy (APT). SUMMARY BACKGROUND DATA: The effectiveness of continuing preoperative aspirin monotherapy in patients undergoing APT in preventing thromboembolic consequences is mostly unknown. METHODS: This prospective multicenter cohort study on the Safety and Feasibility of Gastroenterological Surgery in Patients Undergoing Antithrombotic Therapy (GSATT study) conducted at 14 clinical centers enrolled and screened patients between October 2019 and December 2021. The participants (n=1,170) were assigned to the continued APT group, discontinued APT group, or non-APT group, and the surgical outcomes of each group were compared. Propensity score matching was performed between the continued and discontinued APT groups to investigate the effect of continuing preoperative aspirin therapy on thromboembolic complications. RESULTS: The rate of thromboembolic complications in the continued APT group was substantially lower than that in the non-APT or discontinued APT groups (0.5% vs. 2.6% vs. 2.9%; P=0.027). Multivariate investigation of the entire cohort revealed that discontinuation of APT (P<0.001) and chronic anticoagulant use (P<0.001) were independent risk factors for postoperative thromboembolism. The post-matching evaluation demonstrated that the rates of thromboembolic complications were significantly different between the continued and discontinued APT groups (0.6% vs. 3.3%; P=0.012). CONCLUSIONS: APT discontinuation following elective gastroenterological surgery increases the risk of thromboembolic consequences, whereas continuing preoperative aspirin greatly reduces this risk. The continuation of preoperative aspirin therapy in APT-received patients is considered one of the best alternatives for preventing thromboembolism during elective gastroenterological surgery.

Cetuximab Enhances the Efficacy of MRTX1133, a Novel KRASG12D Inhibitor, in Colorectal Cancer Treatment.

BACKGROUND/AIM: Kirsten Rat Sarcoma viral oncogene homolog (KRAS) has remained undruggable for decades. KRAS has predominantly been used to evaluate the applicability of anti-Epidermal Growth Factor Receptor (EGFR) antibody drugs. However, various KRAS inhibitors have recently emerged. Unfortunately, KRAS inhibitors have not been effective against colorectal cancer. Therefore, this study aimed to determine the effects of MRTX1133, a novel KRASG12D inhibitor, in combination with an anti-EGFR antibody, cetuximab, on signal transduction and cell proliferation. MATERIALS AND METHODS: The KRASG12D-mutated LS513 and KRAS wild-type CACO-2 human colon cancer cell lines were utilized. The KRASG12D mutation was stably transduced into the CACO-2 cells using a retrovirus. We evaluated the effects of the drugs using the CCK-8 assay and assessed the activity of proteins related to the MAPK pathway using western blotting. RESULTS: We demonstrated that the administration of MRTX1133, a novel KRASG12D inhibitor, to KRASG12D-mutated colorectal cancer cells led to feedback activation of the ERK pathway via EGFR activation, inducing drug resistance. Intriguingly, when MRTX1133 was used in combination with cetuximab, KRASG12D-mutant colorectal cancer growth was effectively inhibited, both in vitro and in vivo. CONCLUSION: The combination of MRTX1133 and cetuximab serves as a potential and promising therapeutic approach for colorectal cancer with KRASG12D mutation. KRASG12D is a frequent genetic mutation not only in colorectal cancer, but also in pancreatic and lung cancer, and the results of this study open new avenues for potential treatment of many cancer patients.

Real-world data on induction therapy in patients with transplant-ineligible newly diagnosed multiple myeloma: retrospective analysis of 598 cases from Kansai Myeloma Forum.

To investigate the real-world clinical outcomes and management of novel drug-containing therapies for newly diagnosed multiple myeloma (MM) patients, we retrospectively analyzed data on the first-line treatment for newly diagnosed transplant-ineligible MM patients from Kansai Myeloma Forum, a registry network in Japan. A total of 598 patients treated with novel drugs between March 2007 and February 2018 were analyzed. Regimens used were VD (n = 305), Rd (n = 103), VMP (n = 97), VCD (n = 71), and VRd (n = 22). Younger patients tended to receive VRd or VCD, whereas the regimen with the highest median patient age was Rd. More than three-quarters of patients in the Rd group received a reduced dose of lenalidomide. The Rd and VRd groups had a relatively high incidence of infection and skin complications, and the VMP group had the highest incidence of peripheral neuropathy. Overall response rate did not differ significantly between regimens. Multivariate analysis in all patients revealed several poor prognostic factors, such as poor performance status. Novel drug-containing regimens for newly diagnosed MM showed a durable response with manageable AEs in the real-world setting.

Multiple host targets of Pseudomonas effector protein HopM1 form a protein complex regulating apoplastic immunity and water homeostasis.

Bacterial type III effector proteins injected into the host cell play a critical role in mediating bacterial interactions with plant and animal hosts. Notably, some bacterial effectors are reported to target sequence-unrelated host proteins with unknown functional relationships. The Pseudomonas syringae effector HopM1 is such an example; it interacts with and/or degrades several HopM1-interacting (MIN) Arabidopsis proteins, including HopM1-interacting protein 2 (MIN2/RAD23), HopM1-interacting protein 7 (MIN7/BIG5), HopM1-interacting protein 10 (MIN10/14-3-3ĸ), and HopM1-interacting protein 13 (MIN13/BIG2). In this study, we purified the MIN7 complex formed in planta and found that it contains MIN7, MIN10, MIN13, as well as a tetratricopeptide repeat protein named HLB1. Mutational analysis showed that, like MIN7, HLB1 is required for pathogen-associated molecular pattern (PAMP)-, effector-, and benzothiadiazole (BTH)-triggered immunity. HLB1 is recruited to the trans-Golgi network (TGN)/early endosome (EE) in a MIN7-dependent manner. Both min7 and hlb1 mutant leaves contained elevated water content in the leaf apoplast and artificial water infiltration into the leaf apoplast was sufficient to phenocopy immune-suppressing phenotype of HopM1. These results suggest that multiple HopM1-targeted MIN proteins form a protein complex with a dual role in modulating water level and immunity in the apoplast, which provides an explanation for the dual phenotypes of HopM1 during bacterial pathogenesis.

Impact of the COVID-19 pandemic on mortality trends in Japan: a reversal in 2021? A descriptive analysis of national mortality data, 1995-2021.

OBJECTIVE: The COVID-19 pandemic led to an increase in mortality in most countries in 2020, deviating from prior decreasing trends. In Japan, however, mortality was suggested to decrease in 2020. This study investigated long-term mortality trends and cause-specific contributions, focusing on the period of the COVID-19 pandemic in Japan. DESIGN: We analysed Japanese age-standardised mortality rates (ASMRs) from 1995 to 2021 using vital statistics. MAIN OUTCOME MEASURES: The cause-specific annual ASMR changes were calculated in comparison with the previous year over the abovementioned period. RESULTS: There was a general downward trend in overall ASMR for both sexes until 2020 followed by a small increase in 2021. In men, the all-cause ASMR (per 100 000 persons) decreased from 1352.3 to 1328.8 in 2020 (-1.74% from 2019), and increased to 1356.3 in 2021 in men (+2.07% from 2020). In women, the all-cause ASMR decreased from 746.0 to 722.1 in 2020 (-3.20% from 2019), and increased to 737.9 (+2.19% from 2020) in 2021. ASMRs from malignant neoplasms, pneumonia, accidents and suicide (men only) continued to decrease during the COVID-19 pandemic while the trend of cardiovascular mortality increased in 2021. Analysis of ASMR changes revealed that COVID-19, senility, cardiovascular disease and 'other causes not classified as major causes' contributed to the all-cause mortality increase in 2021. CONCLUSIONS: In Japan, the decreasing trend in overall mortality continued in 2020 despite the COVID-19 pandemic. However, approximately 2% mortality increase was observed in 2021, which was attributable to COVID-19, senility, cardiovascular disease and 'other causes'. The year 2021 was a turning point of mortality trends in Japan, although continued monitoring is warranted.

Transition of deformation modes from bending to auxetic compression in origami-based metamaterials for head protection from impact.

For the protection of the human head by energy absorption structures, a soft mechanical response upon contact with the head is required to mitigate the effect of impact, while a hard mechanical response for highly efficient energy absorption is required to stop the movement of the head. This study realized the opposite mechanical properties during head protection by transitioning the deformation mode from bending to auxetic compression. First, non-linear finite element (FE) models were constructed to numerically reproduce the bending behavior. The calculated force responses agreed well with forces in bending tests. Using the FE models, the EA structures with proper transition of deformation modes were designed and installed in the seat headrests of real vehicles. Head protection was evaluated by dynamic loading in sled testing, in which the force on the head of the crash test dummy was measured. The head injury criterion improved from 274 to 155, indicating the superior performance of the tested structures compared to that achieved by energy absorption structures based on steel plates. Moreover, the deformation of auxetic structures prevented neck bending by holding the head. These findings present new possibilities for effectively protecting the human body by mitigating impact, facilitating energy absorption, and ensuring head stability.