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Background: Tumor cells (TC) participate in tumor progression by altering the immune responses in the tumor microenvironment. However, the clinical relevance and prognostic effect of PD‐L1 expression and tumor‐infiltrating lymphocytes (TILs) in esophageal squamous cell carcinoma (ESCC) are unknown. The purpose of this study was to investigate the interactions and clinical significance of PD‐L1 expression and TILs in ESCC. Methods: Tissue specimens were collected from 126 patients with ESCC who underwent curative esophagectomy. Immunohistochemical analysis and multiplex immunofluorescence for CD4, CD8, CD25, FOXP3, and PD‐L1 in the tumor were used to identify multiple tumor‐infiltrating immune cells (TIIC), Tregs, and TC. Results: PD‐L1 was expressed in tumor cells (PD‐L1 TC). PD‐L1 TIIC and PD‐L1 TC affected the biological behavior of TC. The positive expression rate of PD‐L1 TC and CD8+ TILs was 27.8% (35/126) and 31.7% (40/126), respectively. Kaplan–Meier analysis showed that overall survival (OS) was significantly associated with decreased CD8+ TILs and PD‐L1 TC‐positive expression, which promote ESCC progression and metastasis. Conclusion: Tumor depth, CD8, and PD‐L1 TC were independent prognostic factors in ESCC, and a predictive nomogram with these three risk factors improved the accuracy of predicting OS in patients with ESCC after surgical resection. The conjoint analysis of multiple immune‐related factors is beneficial for stratifying patient survival risk. [ABSTRACT FROM AUTHOR]

Background: Chemotherapy‐induced anorexia is a common occurrence in patients undergoing treatment for advanced lung cancer. However, the relationship between chemotherapy‐induced anorexia and weight loss during platinum‐based chemotherapy combined with immune checkpoint inhibitors is unclear. This study explored the relationship between chemotherapy‐induced anorexia and therapeutic outcomes in patients with stage IV non‐small‐cell lung cancer undergoing platinum‐based chemotherapy combined with immune checkpoint inhibitors. Methods: The study retrospectively reviewed the medical records of 106 patients with stage IV non‐small‐cell lung cancer treated with platinum‐based chemotherapy and immune checkpoint inhibitors between January 2019 and October 2022. The incidence of weight loss and its association with treatment efficacy was assessed in the chemotherapy‐induced anorexia group. Chemotherapy‐induced anorexia, nausea, and vomiting were evaluated using Common Terminology Criteria for Adverse Events v 5.0. Progression‐free and overall survival were used to measure treatment efficacy. Results: Chemotherapy‐induced anorexia was observed in 13.2% of patients. These patients exhibited significant weight loss at 6 and 9 weeks after treatment initiation compared to those in the non‐chemotherapy‐induced anorexia group. Progression‐free and overall survival were shorter in the chemotherapy‐induced anorexia group than in the non‐chemotherapy‐induced anorexia group, but the difference was not statistically significant. Conclusions: Chemotherapy‐induced anorexia was associated with significant weight loss and reduced treatment efficacy in patients with stage IV non‐small‐cell lung cancer. These results highlight the importance of implementing robust supportive care for chemotherapy‐induced anorexia to mitigate weight loss and uphold treatment effectiveness during platinum‐based chemotherapy combined with immune checkpoint inhibitors. [ABSTRACT FROM AUTHOR]

Summary: Leaf mould, caused by Fulvia fulva, is a devastating disease of tomato plants. In many commercial tomato cultivars, resistance to this disease is governed by the Cf‐9 locus, which encodes five paralogous receptor‐like proteins. Two of these proteins confer resistance: Cf‐9C recognises the previously identified F. fulva effector Avr9 and provides resistance during all plant growth stages, while Cf‐9B recognises the yet‐unidentified F. fulva effector Avr9B and provides mature plant resistance only. In recent years, F. fulva strains have emerged that can overcome the Cf‐9 locus, with Cf‐9C circumvented through Avr9 deletion. To understand how Cf‐9B is circumvented, we set out to identify Avr9B.Comparative genomics, transient expression assays and gene complementation experiments were used to identify Avr9B, while gene sequencing was used to assess Avr9B allelic variation across a world‐wide strain collection.A strict correlation between Avr9 deletion and resistance‐breaking mutations in Avr9B was observed in strains recently collected from Cf‐9 cultivars, whereas Avr9 deletion but no mutations in Avr9B were observed in older strains.This research showcases how F. fulva has evolved to sequentially break down the Cf‐9 locus and stresses the urgent need for commercial tomato cultivars that carry novel, stacked resistance genes active against this pathogen. [ABSTRACT FROM AUTHOR]

Automated crack sealing could significantly benefit the maintenance of road pavements, but there is difficulty in depositing the correct volume of sealant material into the hidden crack space. A simulated model of the material flow within a crack space would allow the development of a predictive control scheme, such that the repair robot can apply suitable trajectories and operational parameters to accomplish neatly sealed surfaces. For the first time, the position‐based fluid (PBF) method, a computationally cheap and fast but approximate model of fluid flows, is studied for its feasibility for sealant flow simulation in the robotic injection crack sealing scenario. A Real‐to‐Sim experiment is performed, in which a PBF simulation of sealant in a virtual robotic crack sealing environment is mirrored from the physical lab setup. The fluid simulation is tuned to match the real‐world dynamics through comparison with 132 simulation runs, varying the artificial viscosity parameters U (fluid–fluid viscous interaction) and D (fluid–wall viscous interaction). It was found that U had a varied three‐stage influence on the simulation error while D 's negative influence on the simulation error only effectively applied to fluids satisfying 11\unicode{x0003C}U\unicode{x0003C}100. Through comparing the physical and virtual crack sealing results, the simulation was validated with an average fluid level error of 1.26 mm along a 3.1 mm wide, 16 mm deep and 80 mm long artificial crack, which shows the usefulness of the PBF method for robotic injection sealing. The accuracy and computational requirements of the PBF method are also discussed. [ABSTRACT FROM AUTHOR]

Robotic chefs are a promising technology that can improve the availability of quality food by reducing the time required for cooking, therefore decreasing food's overall cost. This paper clarifies and structures design and benchmarking rules in this new area of research, and provides a comprehensive review of technologies suitable for the construction of cooking robots. The diner is an ultimate judge of the cooking outcome, therefore we put focus on explaining human food preferences and perception of taste and ways to use them for control. Mechanical design of robotic chefs at a practically low cost remains the challenge, but some recently published gripper designs as well as whole robotic systems show the use of cheap materials or off‐the‐shelf components. Moreover, technologies like taste sensing, machine learning, and computer vision are making their way into robotic cooking enabling smart sensing and therefore improving controllability and autonomy. Furthermore, objective assessment of taste and food palatability is a challenge even for trained humans, therefore the paper provides a list of procedures for benchmarking the robot's tasting and cooking abilities. The paper is written from the point of view of a researcher or engineer building a practical robotic system, therefore there is a strong priority for solutions and technologies that are proven, robust and self‐contained enough to be a part of a larger system. [ABSTRACT FROM AUTHOR]

It is often difficult to achieve adequate bone coverage of the cup in total hip arthroplasty in cases of severe developmental dysplasia of the hip (DDH). This study aimed to evaluate the relationship between subluxation percentage of Crowe classification and cup center‐edge (cup‐CE) angle to investigate whether subluxation percentage according to the Crowe classification is a useful indicator for cementless cup placement. Cementless cup placement was simulated in 77 women with DDH in 91 hips (Crowe I, 35 hips; Crowe II, 35 hips; and Crowe III, 21 hips) using computed tomography‐based computer simulation software. The cups were placed at the anatomic hip center (AHC) and 10‐mm high hip center (HHC). The relationship between the subluxation percentage and cup‐CE angle was evaluated using Spearman's rank correlation coefficient. In addition, the cutoff values for the subluxation percentage that satisfied a cup‐CE angle ≥0° were determined using the receiving operating characteristic curve. The cup‐CE angle was negatively correlated with the subluxation percentage in both AHC and 10‐mm HHC (correlation coefficient ρ = −0.542 [p < 0.01] and −0.704 [p < 0.01], respectively). The cutoff values for subluxation percentage that satisfied a cup‐CE angle ≥0° were 56.1% and 73.6% for AHC and 10‐mm HHC, respectively. Cementless cup placement in AHC is difficult in cases with the subluxation percentage ≥56.1%, and HHC reconstruction or femoral structural autograft technique should be considered as an alternative. Moreover, placement at 10 mm above AHC is difficult in cases with subluxation percentage ≥73.6%. [ABSTRACT FROM AUTHOR]

Aim: A new treatment interval for nivolumab administration at 480 mg every 4 weeks, in addition to 240 mg every 2 weeks, was approved in Japan in 2020. Using model‐based evaluation, it was speculated that the effects or safety of nivolumab do not differ between the two treatment intervals; however, real‐world data on nivolumab efficacy, safety, and economic impact are lacking. Accordingly, we aimed to examine the effects of nivolumab treatment intervals (2 weeks vs. 4 weeks) in terms of efficacy, safety, and economic impact in Japanese patients with cancer. Methods: We retrospectively analyzed 126 patients treated with nivolumab. The patients were divided into two groups depending on whether they received nivolumab at 240 mg every 2 weeks (2‐week group) or 480 mg every 4 weeks (4‐week group). Results: Efficacy results found no significant difference between the 4‐ and 2‐week groups considering median overall survival (p = 0.70) and median progression‐free survival (p = 0.57). The incidence of any grade and ≥ grade 3 immune‐related adverse events did not differ between the 4‐week and 2‐week groups (any grade, p = 0.13; ≥ grade 3, p = 0.36). Excluding drug costs, the 4‐week group had significantly lower medical costs than the 2‐week group (2‐week vs. 4‐week: mean, 94,659 JPY [679.0 USD] vs. 58,737 JPY [421.3 USD]; p < 0.05). Conclusion: Collectively, our findings suggest that nivolumab 480 mg every 4 weeks may be more effective than nivolumab 240 mg every 2 weeks in terms of economic impact. [ABSTRACT FROM AUTHOR]

Purpose: Hypertension (HT), dyslipidemia (DL), and diabetes mellitus (DM) are major risk factors for cardiovascular diseases. Despite the wide availability of medications to reduce this risk, poor adherence to medications remains an issue. The aim of this study is to evaluate medication adherence of prevalent users in these disease medications (HT, DL, DM) using claims data. Factors associated with non‐adherence were also examined. Methods: Of 7538 participants of the Tsuruoka Metabolomics Cohort Study, 3693 (HT: 2702, DL: 2112, DM: 661) were identified as prevalent users of these disease medications. Information on lifestyle was collected through a questionnaire. Adherence was assessed by a proportion of days covered (PDC) and participants with PDC ≥0.8 were defined as adherent. Predictors of non‐adherence were determined by performing multivariable logistic regression. Results: Medication adherence differed by treatment status. Among those without comorbidities, those with HT‐only showed the highest adherence (90.2%), followed by those with DM‐only (81.2%) and those with DL‐only (80.8%). Factors associated with non‐adherence in each medication group were skipping breakfast and poor understanding of medications among those with HT medications, females, having comorbidities, having a history of heart disease, and drinking habit among those with DL medications, and good sleep quality and skipping breakfast among those with DM medications. Conclusion: While participants showed high medication adherence, differences were observed across medication groups. The identified predictors of non‐adherence could help target those in need of adherence support. [ABSTRACT FROM AUTHOR]

Background/Purpose: To assess the diagnostic efficacy and safety of endoscopic ultrasound‐guided fine needle biopsy (EUS‐FNB) using a 19‐gauge Franseen needle for autoimmune pancreatitis (AIP). Methods: Twenty patients suspected of having type 1 AIP were prospectively enrolled and underwent EUS‐FNB with a 19‐gauge Franseen needle. Their data were compared with those of historical controls: a total of 29 type 1 AIP patients had EUS‐FNB with a 22‐gauge Franseen needle. Results: Specimens suitable for histological evaluation were obtained from 19 of the 20 patients (95%), and the median total tissue area was 11.9 mm2. The histological diagnosis rate of AIP was 65% (95% CI: 43.2%–82%). Adverse events were observed in three patients (15%), and a switch to 22‐gauge needles occurred during transduodenal puncture in two patients. Compared to those punctured with 22‐gauge needles, patients punctured with 19‐gauge needles had greater prevalence of each characteristic feature of lymphoplasmacytic sclerosing pancreatitis, but the difference was not statistically significant. Conclusions: EUS‐FNB using a 19‐gauge Franseen needle demonstrated favorable performance for the histological diagnosis of AIP and allowed for large tissue samples, potentially facilitating pathological diagnosis. However, during transduodenal puncture, maneuverability is reduced; therefore, the needle may need to be selected according to the puncture site. [ABSTRACT FROM AUTHOR]

Multiple myeloma (MM) is an incurable B‐cell malignancy often accompanied by profound immunodeficiency. Lenalidomide (Len) is an immunomodulatory drug that exerts promising therapeutic effects on MM through the immune system. However, predictive markers related to the effects of Len treatment are not fully understood. This study aimed to identify candidate biomarkers for predicting the clinical efficacy of Len and dexamethasone (Ld) therapy through a comprehensive analysis of serum cytokines. The levels of 48 cytokines in the serum of patients with MM just before Ld therapy (n = 77), at the time of best response (n = 56), and at disease progression (n = 49) were measured and evaluated. Patients with high IL‐18 and M‐CSF levels showed significantly shorter progression‐free survival and overall survival (OS). In contrast, patients with high PDGF‐BB levels had longer survival. Moreover, low levels of G‐CSF, IL‐7, IL‐8, and SDF‐1α were associated with shorter OS after Ld therapy. During Ld therapy, pro‐inflammatory cytokines such as IL‐2Rα, IL‐18, and TNF‐α were decreased, while IFN‐γ was increased. IL‐4 and IL‐6 levels increased during disease progression. In conclusion, this study provides a better understanding of the association between cytokines and the efficacy of Ld therapy as well as the unique changes in cytokines related to inflammatory and immune responses during Ld therapy. [ABSTRACT FROM AUTHOR]

Laparoscopic fenestration is the preferred treatment for symptomatic splenic cysts because it is curative and spleen‐sparing. We report a case of a 25‐year‐old female who underwent laparoscopic fenestration for a giant splenic cyst using a single‐incision plus one‐port approach. She presented to our hospital with repeated vomiting. Imaging showed a 23 × 18 cm splenic cyst with no solid components, strongly compressing the stomach to the right side. Laparoscopic fenestration was initiated through a 2.5‐cm umbilical incision, and a 5‐mm port was added in the left abdomen intraoperatively. The drain placement was deemed necessary to prevent abscess formation and post‐operative bleeding because of a thick cyst component and unexpectedly thick wall. Splenic cysts are typically benign and commonly develop in young people, hence, organ preservation and cosmetic results are crucial. Laparoscopic fenestration using single‐incision plus one‐port is considered to be an appropriate procedure for giant splenic cysts with non‐serous contents. [ABSTRACT FROM AUTHOR]

Aim: To evaluate the effectiveness of an individualized nutritional education program in promoting adequate nutrient intake in pregnant women. Methods: A stratified randomized controlled trial was conducted. Participants were stratified by factors affecting the primary outcome and randomly assigned to the intervention or control groups. Intervention group participants received an individualized 30‐min booklet‐based education program in their 2nd and 3rd trimesters; the control group received usual care. The primary outcome was protein intake after the intervention, which was compared between the intervention and control groups. Secondary outcomes included comparing the amount of increase of protein before and after the intervention. Nutrient intake was measured using a self‐administered short dietary history questionnaire, and analyses of covariance and t tests were performed. Results: Of the 130 participants, 66 were assigned to the intervention group and 64 to the control group. There was no difference in protein intake between the two groups after the intervention (p =.051, 95% CI [−0.021, 12.4]). Comparing the increase in protein intake before and after intervention, the intervention group was 7.4 g/day higher than that of the control group (p =.040; F = 4.31; effect size = 0.36). Conclusions: The primary outcome, a comparison of protein intake between the groups after the program, revealed no significant differences. However, on comparing the amount of protein increase before and after the intervention, the intervention group's increase was significantly higher than that of the control group. Results indicate the potential for individualized face‐to‐face interventions for pregnant women in Japan. [ABSTRACT FROM AUTHOR]

The APOE4 allele is recognized as a significant genetic risk factor to Alzheimer's disease (AD) and influences longevity. Nonetheless, some APOE4 carriers exhibit resistance to AD even in advanced age. Humanin, a mitochondrial‐derived peptide comprising 24 amino acids, has variants linked to cognitive resilience and longevity. Our research uncovered a unique humanin variant, P3S, specifically enriched in centenarians with the APOE4 allele. Through in silico analyses and subsequent experimental validation, we demonstrated a strong affinity between humanin P3S and APOE4. Utilizing an APOE4‐centric mouse model of amyloidosis (APP/PS1/APOE4), we observed that humanin P3S significantly attenuated brain amyloid‐beta accumulation compared to the wild‐type humanin. Transcriptomic assessments of mice treated with humanin P3S highlighted its potential mechanism involving the enhancement of amyloid beta phagocytosis. Additionally, in vitro studies corroborated humanin P3S's efficacy in promoting amyloid‐beta clearance. Notably, in the temporal cortex of APOE4 carriers, humanin expression is correlated with genes associated with phagocytosis. Our findings suggest a role of the rare humanin variant P3S, especially prevalent among individuals of Ashkenazi descent, in mitigating amyloid beta pathology and facilitating phagocytosis in APOE4‐linked amyloidosis, underscoring its significance in longevity and cognitive health among APOE4 carriers. [ABSTRACT FROM AUTHOR]

Unsaturated soil contains pore air, some of which becomes entrapped in the soil layer during the infiltration process. Such entrapped pore air in the soil layer inhibits infiltration, decreases hydraulic conductivity, and causes erroneous estimates of groundwater response. Experimental studies suggest an effect of compressed entrapped pore air on stream discharge. However, few studies have investigated the behaviour of pore air in the field, and no method for measurement of pore‐air behaviour has been established. We measured pore‐air pressure (Pair) with a simple handmade probe, combined with atmospheric pressure (Patm) and groundwater level. The entrapment and compression of pore air were detected based on the pressure difference (ΔP = Pair – Patm). Observations were conducted for approximately 1 year in two small headwater catchments (TC and HA, which have differences in soil depth and groundwater level dynamics) in Ibaraki Prefecture, Japan. Positive responses of ΔP during some rainfall events were confirmed at both TC and HA. Pore‐air entrapment occurred even during weak rainfall events with rainfall intensity of <10 mm/h. During a typhoon event in October 2019, a maximum ΔP of 3.9 kPa was observed at HA. The pore pressure increase recorded by the tensiometer was mostly explained by the increase in ΔP, which was supported by the soil moisture data. Therefore, we concluded that our handmade measurement system could successfully measure Pair and detect pore‐air entrapment in the field. This showed that Pair is not negligible. Total event rainfall was related to the maximum ΔP. It also showed that the rise in the groundwater level plays a significant role in pressurization of the entrapped pore air. We present the first field data demonstrating the effect of groundwater level rise on the pressurization of entrapped Pair. [ABSTRACT FROM AUTHOR]

Introduction: Hybrid total laparoscopic hysterectomy combines conventional laparoscopic surgery and robot‐assisted devices: the camera and assistant forceps are operated by a robotic device, whereas the surgeon performs laparoscopic procedures, enabling surgery with a completely fixed field of view and significantly reducing errors in forceps grasping and needle misalignment. Here, we examined whether using two arms of the Hugo™ robot‐assisted surgery system, one for the camera and one for the assistant, would improve surgical accuracy compared with conventional total laparoscopic hysterectomy. Materials and Surgical Technique: The surgical system reduced surgeon errors in grasping the forceps during training and stabilized forceps operation. Compared with conventional laparoscopic surgery, the use of the surgical system did not result in different operative durations. The stable surgical procedure was considered a major advantage. Discussion: This new technique involving new equipment can improve surgeon training and performance. In the future, we will develop new techniques to improve surgical performance. [ABSTRACT FROM AUTHOR]

Background: The da Vinci surgical systems (X and Xi) are fourth‐generation systems marketed by Intuitive Inc. The X system is less expensive than the Xi system. This study compared the surgical outcomes of patients who underwent hysterectomy using the X and Xi systems. Methods: Data from 172 patients who underwent robot‐assisted total hysterectomies by four surgeons between April 2019 and March 2023 were retrospectively analyzed in a single‐center study. The patients were divided into two groups based on the surgical system used. Approval was granted by the Institutional Review Board of the Tottori University Hospital (22A134). All patients provided opt‐out consent in accordance with the institutional guidelines. Results: Operative time (126.6 ± 29.5 for X, 138.2 ± 38.5 for Xi, p =.227) and console time (92.9 ± 27.0 for X, 105.5 ± 34.7 for Xi, p =.089) were insignificantly shorter in group X than in group Xi after propensity score matching for age, body mass index, nulliparity, previous history of abdominal or pelvic surgery, preoperative diagnosis, and surgical approach. No significant differences between X and Xi were observed in a subgroup analysis of patients who underwent robot‐assisted total laparoscopic hysterectomy without lymphadenectomy (operative time: 199.0 ± 26.5 for X, 221.5 ± 45.1 for Xi, p =.227; console time: 162.1 ± 25.0 for X, 178.3 ± 0.314 for Xi, p =.314). Conclusion: Perioperative outcomes for the X and Xi da Vinci surgical systems were equivalent. The cost‐effective X system may allow the widespread use of robotic surgeries. [ABSTRACT FROM AUTHOR]

Concurrent direct and indirect inguinal, femoral, and obturator hernias are rare. This case report describes a rare case treated using the laparoscopic approach. A 68‐year‐old female patient presented with a moving left inguinal lump and pain. Physical examination and abdominal computed tomography scan revealed the coexistence of a left inguinal hernia or Nuck canal hydrocele and a left femoral hernia. The patient underwent laparoscopic transabdominal preperitoneal repair, and all four orifices were covered with one mesh. The patient was discharged on the second postoperative day without any complications. The concurrent presence of four hernias on the same side is rare and has not been previously reported. The laparoscopic approach is useful in such cases because it allows visualization of multiple hernia orifices from the intra‐abdominal cavity. [ABSTRACT FROM AUTHOR]

Inter‐catchment groundwater flow (IGF) plays an essential role in streamflow generation and water quality in forested headwaters. Multiple factors are thought to contribute to IGF, including climate, topographical, and geological factors. However, studies have not clarified the relationships between IGF and catchment properties in the headwater catchments due to the lack of observational data at scales smaller than 100 ha. This study examined possible factors influencing IGF using random forest analysis based on annual water balance data from 152 forested catchments ranging from 0.09 to 9400 ha in Japan. The results showed that catchment scale had the greatest influence on IGF, and IGF tended to decrease with increasing catchment area at scales of less than 10 ha. The average IGF stabilized around zero in catchments greater than 10 ha. The averaged IGF trend with catchment scale indicated more outward groundwater flow in catchments smaller than 10 ha, but no relationship between IGF and catchment size in catchments larger than 10 ha. The variability in IGF decreased with catchment size and was lowest at 10–100 ha. The decrease in variability in catchments less than 100 ha was mainly due to river confluence and the increased variability in catchments larger than 100 ha indicated potential observation errors increase in catchments of this size. Plain Language Summary: Inter‐catchment groundwater flow (IGF) refers to groundwater flux across surface topographic boundaries. Recent studies have clarified that IGF significantly affects streamflow generation and water quality. However, direct observation of IGF is difficult, and the mechanisms underlying IGF are not fully understood. This study examined the factors influencing IGF, as well as its scale dependence and variability based on water balance data from 152 forested catchments ranging from 0.09 to 9400 ha in Japan. This showed that catchment area had the greatest influence on IGF. Groundwater tended to flow out of catchments smaller than 10 ha, and stabilized in those larger than 10 ha. Variability in the IGF decreased with catchment size at less than 100 ha. These results suggest that on the scale of hillslope and headwater catchments, IGF has a great influence on streamflow generation. Key Points: We examined the factors influencing inter‐catchment groundwater flow (IGF) using water balance data for 152 forest catchments in JapanCatchment scale was the factor with the greatest influence on the IGFGroundwater tends to flow out of catchments smaller than 10 ha and IGF approaches zero when the catchment area exceeds 10 ha [ABSTRACT FROM AUTHOR]

Aim: Advanced glycation end‐products (AGEs) are irreversibly and heterogeneously formed compounds during the non‐enzymatic modification of macromolecules, such as proteins. Aging and lifestyle habits, such as high‐fat and high‐protein diets, and smoking, promote AGEs accumulation. This study aimed to investigate the relationship between fall risk and AGEs in community‐dwelling older adults. Methods: This cross‐sectional study included patients from the 2022 Yakumo Study who were evaluated for fall risk index 5‐items version, locomotive syndrome stage and AGEs. AGEs were evaluated using Skin autofluorescence (SAF) measured by the AGE reader (DiagnOptics Technologies BV, Groningen, the Netherlands). We divided the participants into two groups according to the presence or absence of fall risk (fall risk index 5‐items version ≥6 or not), and investigated the factors associated with fall risk. Results: The fall risk group had a higher age and SAF, and a higher proportion of locomotive syndrome stage >2 than the without fall risk group in patients aged ≥65 years (P < 0.01). The multivariate logistic regression analysis after adjustment of age, sex and body mass index showed that locomotive syndrome stage ≥2 and SAF were independent associators of fall risk in older adults (odds ratio 3.26, P < 0.01, odds ratio 2.96, P < 0.05, respectively). The optimal cutoff value of the SAF for fall risk was 2.4 (area under the curve 0.631; 95% CI 0.53–0.733; sensitivity 0.415; specificity 0.814; P < 0.05). Conclusion: The accumulation of AGEs in skin tissues can be used to screen for fall risk comprehensively. Geriatr Gerontol Int 2024; 24: 517–522. [ABSTRACT FROM AUTHOR]

Key Clinical Message: Most Japanese patients naturally infected with COVID‐19 were infected after mRNA vaccination, and many maintained high antibody titers due to hybrid immunity. The significance of additional vaccination in hybrid‐immunized cases is highly questionable. Spontaneous infection with severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) after mRNA vaccination causes a marked increase in antibody titer because of the combined effect of vaccine and infection ("hybrid immunity"). In this study, we discuss the significance of the mRNA vaccine booster inoculation that has been repeatedly performed in Japan. We describe the temporal trends of antibody titers in cases in which antibody titers were markedly increased by hybrid immunization. The antibody titer increased with hybrid immunization and tended to decrease with time. However, several cases maintained high antibody titers for approximately 1 year after coronavirus disease 2019 (COVID‐19) diagnosis, even without booster vaccination. Most Japanese patients naturally infected with COVID‐19 were infected after mRNA vaccination, and many maintained high antibody titers due to hybrid immunity. The significance of additional vaccination in hybrid‐immunized cases is highly questionable regarding cost‐effectiveness and risk–benefit. [ABSTRACT FROM AUTHOR]

Evidence is accumulating that osteal macrophages, in addition to bone‐resorbing osteoclasts and bone‐forming osteoblasts, participate vitally in bone remodeling process. Oncostatin M (OSM), an inflammatory cytokine belonging to interleukin‐6 superfamily, is recognized as an essential factor secreted by osteal macrophages to orchestrate bone remodeling. Osteoprotegerin (OPG) produced by osteoblasts regulates osteoclastogenesis. We have reported that bone morphogenetic protein‐4 (BMP‐4) stimulates OPG synthesis in MC3T3‐E1 osteoblast‐like cells, and that SMAD1/5/8(9), p38 mitogen‐activated protein kinase (MAPK), and p70 S6 kinase are involved in the OPG synthesis. The present study aims to investigate the effect of OSM on the synthesis of OPG stimulated by BMP‐4 in osteoblasts. OSM suppressed the release and the mRNA expression of OPG upregulated by BMP‐4 in MC3T3‐E1 cells. Neither the BMP‐4‐induced phosphorylation of SMAD1/5/9 nor that of p38 MAPK was affected by OSM. On the other hand, the phosphorylation of p70 S6 kinase stimulated by BMP‐4 was considerably suppressed by OSM. These results strongly suggest that OSM suppresses the BMP‐4‐stimulated OPG synthesis via inhibition of the p70 S6 kinase‐mediated pathway in osteoblast‐like cells. Significance Statement: Oncostatin M (OSM), a cytokine of the interleukin‐6 superfamily, modulates bone remodeling. Osteoprotegerin (OPG) secreted from osteoblasts regulates osteoclastogenesis. We previously showed that bone morphogenetic protein‐4 (BMP‐4) activates SMAD1/5/8(9), p38 mitogen‐activated protein kinase, and p70 S6 kinase, resulting in OPG synthesis in osteoblast‐like MC3T3‐E1 cells. In the present study, we investigated the effects of OSM on the BMP‐4‐induced synthesis of OPG in these cells. Our results strongly suggest that OSM suppresses OPG synthesis by inhibiting the p70 S6 kinase‐mediated pathway in osteoblasts. [ABSTRACT FROM AUTHOR]

Aims: Non‐dilated left ventricular cardiomyopathy (NDLVC) was proposed as a new category of cardiomyopathy that included patients with non‐left ventricular (LV) dilatation, LV wall motion abnormality, or LV scar. However, the clinical background and event rates of NDLVC were unclear. The aim of this study was to examine the characteristics and event rates of patients with NDLVC and reduced LV ejection fraction (NDLVC–REF) in comparison with those with dilated cardiomyopathy (DCM). Methods and results: We retrospectively included 363 patients with newly diagnosed non‐ischaemic cardiomyopathy and reduced LV ejection fraction (<50%) between December 2004 and January 2018. Patients who did not have LV dilatation (LV dimension index of ≦31 mm/m2 in men and ≦34 mm/m2 in women) were categorized as NDLVC–REF (n = 80, 22.2%), and the remaining patients were categorized as DCM. Cardiac events were defined as sudden cardiac death and rehospitalization for heart failure. Patients with NDLVC–REF had a higher prevalence of atrial fibrillation and a higher LV ejection fraction than those with DCM at baseline. LV ejection fraction was higher and LV end‐diastolic diameter was smaller in patients with NDLVC–REF than in those with DCM at all time points after diagnosis. During the median follow‐up period of 68.8 months (interquartile range: 33.0–93.7 months), 44 patients experienced cardiac events. The Kaplan–Meier curves showed no significant differences in the probability of cardiac events among NDLVC–REF and DCM patients (P = 0.349). However, patients with NDLVC–REF and LV dilatation after diagnosis (14%) had a higher risk of cardiac events than those with NDLVC–REF without LV dilatation (P = 0.049). Conclusions: There was no significant difference in the incidence of cardiac events between NDLVC–REF and DCM. Among NDLVC–REF patients, 18% of patients who showed LV dilatation after diagnosis had poor outcomes. Therefore, both NDLVC–REF and DCM patients may require equivalent attention to follow‐up and regular assessment of LV function. [ABSTRACT FROM AUTHOR]

Background and Objective: Interstitial lung disease (ILD) is characterized by dyspnoea on exertion and exercise‐induced hypoxaemia. High‐flow nasal cannula (HFNC) therapy reduces the respiratory workload through higher gas flow and oxygen supplementation, which may affect exercise tolerance. This study aimed to examine the effects of oxygen and gas flow rates through HFNC therapy on exercise tolerance in ILD patients. Methods: We conducted three‐treatment crossover study. All ILD patients performed the exercises on room air (ROOM AIR setting: flow, 0 L/min; fraction of inspired oxygen [FiO2], 0.21), HFNC (FLOW setting: flow 40 L/min, FiO2 0.21), and HFNC with oxygen supplementation (FLOW + OXYGEN setting: flow 40 L/min, FiO2 0.6). The primary endpoint was the endurance time, measured using constant‐load cycle ergometry exercise testing at a peak work rate of 80%. Results: Twenty‐five participants (10 men, 71.2 ± 6.7 years) were enrolled. The increase in exercise duration between the ROOM AIR and FLOW was 46.3 s (95% CI, −6.1 to 98.7; p = 0.083), and the FLOW and FLOW + OXYGEN was 91.5 s (39.1–143.9; p < 0.001). The percutaneous oxygen saturation (SpO2) at rest was significantly higher with the FLOW + OXYGEN setting than with the ROOM AIR and FLOW settings, and the difference persisted during exercise. At equivalent time points during exercise, the SpO2 with the FLOW setting was significantly higher than that with the ROOM AIR setting. Conclusion: Oxygen supplementation in HFNC therapy improved exercise tolerance and SpO2. We found that gas flow alone did not improve exercise tolerance, but improved SpO2 during exercise. [ABSTRACT FROM AUTHOR]

A larger left bundle branch (LBB) potential or LBB current of injury (COI) indicates a low LBB capture threshold in LBB pacing. During LBB pacing in an 85‐year‐old woman, achieving a low LBB capture threshold did not initially present with a larger LBB potential or LBB COI, but rather with a new initial negative deflection in a ventricular electrogram. LBB COI gradually developed over 7 min thereafter, which suggested that the lead tip had reached the left ventricular subendocardium. Therefore, this negative deflection may be the first sign to avoid further lead rotation. [ABSTRACT FROM AUTHOR]

Hypoxia is a common feature of solid tumors. However, the impact of hypoxia on immune cells within tumor environments remains underexplored. Carbonic anhydrase 9 (CA9) is a hypoxia‐responsive tumor‐associated enzyme. We previously noted that regardless of human CA9 (hCA9) expression, hCA9‐expressing mouse renal cell carcinoma RENCA (RENCA/hCA9) presented as a "cold" tumor in syngeneic aged mice. This study delves into the mechanisms behind this observation. Gene microarray analyses showed that RENCA/hCA9 cells exhibited elevated mouse serpinB9, an inhibitor of granzyme B, relative to RENCA cells. Corroborating this, RENCA/hCA9 cells displayed heightened resistance to antigen‐specific cytotoxic T cells compared with RENCA cells. Notably, siRNA‐mediated serpinB9 knockdown reclaimed this sensitivity. In vivo tests showed that serpinB9 inhibitor administration slowed RENCA tumor growth, but this effect was reduced in RENCA/hCA9 tumors, even with adjunctive immune checkpoint blockade therapy. Further, inducing hypoxia or introducing the mouse CA9 gene upregulated serpinB9 expression, and siRNA‐mediated knockdown of the mouse CA9 gene inhibited the hypoxia‐induced induction of serpinB9 in the original RENCA cells. Supernatants from RENCA/hCA9 cultures had lower pH than those from RENCA, suggesting acidosis. This acidity enhanced serpinB9 expression and T cell apoptosis. Moreover, coculturing with RENCA/hCA9 cells more actively prompted T cell apoptosis than with RENCA cells. Collectively, these findings suggest hypoxia‐associated CA9 not only boosts serpinB9 in cancer cells but also synergistically intensifies T cell apoptosis via acidosis, characterizing RENCA/hCA9 tumors as "cold." [ABSTRACT FROM AUTHOR]

Advanced gastric and gastroesophageal junction cancers (GC/GEJCs) harbor diverse molecular signatures, highlighting the need for intricate evaluations to identify potential therapeutic targets. Although whole‐transcriptome sequencing (WTS) has emerged as a useful tool for understanding these molecular intricacies, its clinical implications have yet to be fully elucidated. This study evaluated the correlation between immunohistochemistry (IHC) and WTS, compared their clinical significance, and identified potential therapeutic targets undetectable through IHC alone. We enrolled 140 patients with advanced GC/GEJC and assessed them using IHC for six pivotal biomarkers: claudin‐18 (CLDN18), human epidermal growth factor receptor 2 (HER2), multiple receptor tyrosine kinases (RTKs), and programmed death ligand 1 (PD‐L1). Concurrently, WTS was employed as part of the analyses in MONSTAR‐SCREEN‐2, a multicenter multiomics study. IHC analysis revealed 16.4% HER2, 39.3% CLDN18 (2+/3 + ≥75%), and 15.8% PD‐L1 (combined positive score ≥ 10) positivity, among other molecular markers. Significant correlations were observed between IHC and WTS for all six pivotal biomarkers. Among nineteen HER2 IHC‐positive patients treated with anti‐HER2 therapeutics, ERBB2 status in WTS was significantly associated with progression‐free survival (ERBB2‐high vs. ‐low: median 9.0 vs. 5.6 months, log‐rank p = 0.046). IHC‐based molecular profiling revealed significantly high expression of CLDN18 in RTK‐negative patients, with 78.4% positive for either CLDN18 or PD‐L1. Additionally, WTS revealed elevated expression of pivotal biomarkers in patients displaying negative targetable biomarkers via IHC. Our findings highlighted the significant correlation between IHC and WTS, reinforcing the clinical utility of WTS. A subset with IHC‐negative but WTS‐positive status may benefit from specific biomarker‐targeted therapies. [ABSTRACT FROM AUTHOR]

Quizartinib is a potent, oral, second‐generation, selective type II FMS‐like receptor tyrosine kinase 3 (FLT3) inhibitor. It has shown improved overall survival in a randomized, multinational, Phase 3 (QuANTUM‐First) study in patients with FLT3‐internal tandem duplication (ITD)‐positive newly diagnosed acute myeloid leukemia. We conducted 2 Phase 1b studies in Japan and China to evaluate the safety, pharmacokinetics, and efficacy of quizartinib in combination with standard induction and consolidation chemotherapy in patients with newly diagnosed acute myeloid leukemia. Quizartinib was started at a dose level of 20 mg/day and then escalated to 40 mg/day, the dose used in the Phase 3 study. Seven patients were enrolled according to the 3 + 3 dose‐escalation method in each study, including 3 patients who were FLT3‐ITD positive. No dose‐limiting toxicities were observed at dose levels up to 40 mg/day in both studies. Grade 3 or higher, quizartinib‐related, treatment‐emergent adverse events included febrile neutropenia, hematologic toxicities, and infections. QT prolongation on electrocardiogram was observed in 5 patients. The pharmacokinetics of quizartinib and its metabolite AC886 were similar between the studies and consistent with previous findings in the United States. We confirmed the tolerability of Japanese and Chinese patients to the dose of quizartinib and chemotherapy regimens used in the QuANTUM‐First study. [ABSTRACT FROM AUTHOR]

Research Highlights A profound developmental experience is the emergence of adolescent romantic relationships and first feelings of love. However, the daily nature of feeling loved in adolescents’ everyday lives is poorly understood. We investigated how daily stress severity was associated with adolescents’ levels of feeling loved and whether romantic partner support moderated these associations. Furthermore, we investigated this for non‐interpersonal and interpersonal stressors. N = 97 mixed‐gender adolescent romantic couples (age M = 16.38, SD = 1.02) from an ethnically diverse sample (42.2% Hispanic/Latino/a/x, 44.7% White) participated in dyadic diary assessments twice a week for 12 consecutive weeks. Both partners independently completed open‐ended questions about a daily stressor, indicating stress severity, perceived partner support, and feeling loved. Daily stressors were coded for non‐interpersonal and various types of interpersonal stressors. Results from the dyadic multilevel model showed that days with lower than average support from a romantic partner amplify the adverse effects of stress severity on feeling loved, especially when the partner is involved in the stressor. We discuss the spillover of stress in romantic relationships and the stress‐buffering functions of adolescent romantic partner support. Adolescent romantic partners are potentially essential regulators of stress, increasing adolescents’ feelings of love. Romantic love is central in adolescents’ lives; we showed that adolescents generally feel loved by romantic partners. Feeling loved fluctuates daily as adolescents feel less loved on stressful days. However, when adolescents perceive their partner as supportive, there is no association between stress and feeling loved. Partner support is protective for feeling loved. The current study provides essential insights into when adolescents and why adolescents feel loved. [ABSTRACT FROM AUTHOR]

As the number of bariatric and metabolic surgeries being performed is increasing, the importance of revision surgeries is escalating. In this report, we describe a case of revision surgery performed 30 years after vertical banded gastroplasty (VBG), including a review of the surgical techniques. The patient was a male in his 50s who had previously undergone VBG for morbid obesity (body mass index of 72.6 kg/m2), resulting in gradual weight loss. Twenty‐eight years later, reflux symptoms due to stenosis of the mesh area developed. Despite conservative treatment, the symptoms recurred, and aspiration pneumonia developed. Gastrojejunal and Y‐anastomoses were performed laparoscopically. Postoperatively, the patient progressed well with no weight regain. In revision surgery, it is essential to accurately assess the patient's pathophysiology, as the surgical technique must consider improvement in symptoms, risk of weight regain, and the need for observation of the residual stomach. [ABSTRACT FROM AUTHOR]

Objectives: In this study we aimed to develop an artificial intelligence‐based model for predicting postendoscopic retrograde cholangiopancreatography (ERCP) pancreatitis (PEP). Methods: We retrospectively reviewed ERCP patients at Nagoya University Hospital (NUH) and Toyota Memorial Hospital (TMH). We constructed two prediction models, a random forest (RF), one of the machine‐learning algorithms, and a logistic regression (LR) model. First, we selected features of each model from 40 possible features. Then the models were trained and validated using three fold cross‐validation in the NUH cohort and tested in the TMH cohort. The area under the receiver operating characteristic curve (AUROC) was used to assess model performance. Finally, using the output parameters of the RF model, we classified the patients into low‐, medium‐, and high‐risk groups. Results: A total of 615 patients at NUH and 544 patients at TMH were enrolled. Ten features were selected for the RF model, including albumin, creatinine, biliary tract cancer, pancreatic cancer, bile duct stone, total procedure time, pancreatic duct injection, pancreatic guidewire‐assisted technique without a pancreatic stent, intraductal ultrasonography, and bile duct biopsy. In the three fold cross‐validation, the RF model showed better predictive ability than the LR model (AUROC 0.821 vs. 0.660). In the test, the RF model also showed better performance (AUROC 0.770 vs. 0.663, P = 0.002). Based on the RF model, we classified the patients according to the incidence of PEP (2.9%, 10.0%, and 23.9%). Conclusion: We developed an RF model. Machine‐learning algorithms could be powerful tools to develop accurate prediction models. [ABSTRACT FROM AUTHOR]

Generally, in vertebrates, the first step toward fertilization is the ovulation of mature oocytes, followed by their binding to sperm cells outside of the ovary. Exceptionally, the oocytes of poeciliid fish are fertilized by sperm cells within the follicle, and the developmental embryo is subsequently released into the ovarian lumen before delivery. In the present study, we aimed to identify the factor(s) responsible for intrafollicular fertilization in a viviparous teleost species, Poecilia reticulata (guppy). Sperm tracking analysis in this regard indicated that in this species, sperm cells reached immature oocytes including the germinal vesicle, and the insemination assay indicated that the immature oocytes robustly adhered to the sperm cells; similar binding was not observed in Danio rerio (zebrafish) and Oryzias latipes (medaka). We also identified the Ly6/uPAR protein bouncer as the factor responsible for the observed sperm binding activity of the immature oocytes in this species. The recombinant bouncer peptide acted as an inhibitory decoy for the sperm–oocyte binding in guppy. On the other hand, ectopic expression of guppy bouncer in zebrafish oocytes resulted in interspecific sperm–oocyte binding. These results argue that bouncer is responsible for sperm–immature oocyte binding. Our findings highlight the unique reproductive strategies of guppy fish and enhance our understanding of the diverse reproductive mechanisms in vertebrates. [ABSTRACT FROM AUTHOR]

Holonomic mobile micromanipulators driven by piezoelectric actuators offer precision and compact design. However, attaining both high speed and positioning repeatability with sufficient load capacity poses challenges, given that lightweight robots are susceptible to nonuniform driving surfaces and external forces. A holonomic beetle (HB) is proposed to realize a wide range, compact size, precise holonomic motion, automatic micromanipulation, and high‐speed movement simultaneously. Inspired by the biological makeup of a Rhinoceros Beetle, a length, weight, and load capacity of 8 cm, 74 g, and of 2000 g, respectively, are used. The HB is a two‐legged robot with a pseudoalternating tripod gait locomotion principle, with five piezoelectric actuators for XYθ displacement and switching of the contact leg. It achieves maximum walking velocities of 11.6 mm s−1 for translational motion and 19.3 deg s−1 for rotation, with a displacement resolution of 12 nm. Notably, under open‐loop control, the HB demonstrates high repeatability with a coefficient of variation of 0.3%. It exhibits the capability to climb 30°‐inclined surfaces, traverse flat surfaces with 0.1 mm bumps, and navigate 30 mm pits. Furthermore, the HB showcases practical automatic micromanipulation through visual servo control and machine learning, presenting potential applications in biomedical and microassembly fields. [ABSTRACT FROM AUTHOR]

Materials that intrinsically exhibit localized surface plasmon resonance (LSPR) in the visible region have been predominantly researched on nanoparticles (NPs) composed of coinage metals, namely Au, Ag, and Cu. Here, as a coinage metal‐free intermetallic NPs, colloidal PtIn2 NPs with a C1 (CaF2‐type) crystal structure are synthesized by the liquid phase method, which evidently exhibit LSPR at wavelengths similar to face‐centered cubic (fcc)‐Au NPs. Computational simulations pointed out differences in the electronic structure and photo‐excited electron dynamics between C1‐PtIn2 and fcc‐Au NPs; reduces interband transition and stronger screening with smaller number of bound d‐electrons compare with fcc‐Au are unique origins of the visible plasmonic nature of C1‐PtIn2 NPs. These results strongly indicate that the intermetallic NPs are expected to address the development of alternative plasmonic materials by tuning their crystal structure and composition. [ABSTRACT FROM AUTHOR]

Background: Brachycephalic dogs display sleep‐disordered breathing (SDB). The risk factors for SDB remain unknown. Objectives: To identify risk factors for SDB. We hypothesized that brachycephaly, increasing severity of brachycephalic obstructive airway syndrome (BOAS), excess weight, and aging predispose to SDB. Animals: Sixty‐three privately owned pet dogs were prospectively recruited: 28 brachycephalic and 35 normocephalic (mesaticephalic or dolicocephalic) dogs. Methods: Prospective observational cross‐sectional study with convenience sampling. Recording with the neckband was done over 1 night at each dog's home. The primary outcome measure was the obstructive respiratory event index (OREI). Body condition score (BCS) was assessed, and BOAS severity was graded for brachycephalic dogs. Results: Brachycephaly was a significant risk factor for high OREI value (ratio of the geometric means 5.6, 95% confidence interval [CI] 3.2‐9.9; P <.001) but aging was not (1.1, 95% CI 1.0‐1.2; P =.2). Excess weight, defined as a BCS of over 5/9, (3.5, 95% CI 1.8‐6.7; P <.001) was a significant risk factor. In brachycephalic dogs, BOAS‐positive class (moderate or severe BOAS signs) was a significant risk factor (2.5, 95% CI 1.1‐5.6; P =.03). Conclusions and Clinical Importance: Brachycephaly decreases welfare in a multitude of ways, including disrupting sleep. Brachycephaly, increasing severity of BOAS and excess weight are risk factors for obstructive SDB. [ABSTRACT FROM AUTHOR]

As differences in sex pheromones usually act as a barrier against interspecific mating, the fact that the closely related moths Xylena fumosa (Butler) and X. formosa (Butler) (Lepidoptera: Noctuidae: Xyleninae) are commonly attracted to the sex pheromone lure for Helicoverpa armigera (Hübner) (Lepidoptera: Noctuidae: Heliothinae) seems unlikely, suggesting that some mechanisms exist between them to mitigate a potential reproductive interference in pheromone communications. Thus, we examined the overlaps in ecological niches of the two species, and their attractiveness to commercial pheromone lures for other moths, through pheromone trap surveys and published reports. Long‐term field surveys using traps baited with five to six types of artificial sex pheromone lures including those designed for H. armigera, and information in published works revealed that there was a nonnegligible overlap between the two species in terms of seasonal timing of captures, geographic habitats and host plants. These factors, therefore, did not appear to provide conclusive evidence mitigating reproductive interference. However, there was a slight but significant difference between them in the trends of attraction to different artificial pheromone lures; X. formosa was attracted albeit in a small number to the lures for Plutella xylostella (Linnaeus) (Lepidoptera: Plutellidae), whereas X. fumosa was only attracted to those for H. armigera. This suggests that differences in pheromone composition, rather than differences in temporal and spatial distributions, between the two species could play a more significant role in premating reproductive isolations. [ABSTRACT FROM AUTHOR]

Clarifying the influence of disturbances by biotic and abiotic agents on long‐term changes in forest structure and demographic rates is an important task of forest ecology. Here, we investigated changes in forest structure and demographic rates and the effects of biotic and abiotic factors (sika deer, ambrosia beetle, neighborhood trees, and indices of strong wind and wetness) in a 4‐ha long‐term ecological study plot in a lowland warm temperate rain forest on Yakushima Island, Japan, from 1996 to 2019 for three regeneration groups related to gap dynamics (gap demander: GD, light shade tolerant: LS, and strong shade tolerant: SS). GD had relatively lower recruitment and survival than LS and/or SS. Changes in demographic rates were not significantly correlated with those in the index of strong wind in any regeneration group. The effects of sika deer on demographic rates did not differ among groups. Stems of Fagaceae species belonging to LS attacked by ambrosia beetles recorded in 2013 did not significantly differ in RGR and survival rates. Our results indicate that despite the relatively long monitoring period of 23 years, we did not detect significant effects of strong winds on demographic rates among regeneration groups, and shade‐tolerant species (LS and SS) showed better demographic performance than light‐demanding species (GD) and an increase in total basal area over time. We need longer monitoring of forest dynamics to understand forest responses to disturbances considering several factors, including the time lag of demographic responses to disturbances and the long‐term effects of disturbances. [ABSTRACT FROM AUTHOR]

PTPRF interacting protein alpha 1 (PPFIA1) encodes for liprin‐α1, a member of the leukocyte common antigen–related protein tyrosine phosphatase (LAR‐RPTPs)‐interacting protein family. Liprin‐α1 localizes to adhesive and invasive structures in the periphery of cancer cells, where it modulates migration and invasion in head and neck squamous cell carcinoma (HNSCC) and breast cancer. To study the possible role of liprin‐α1 in anticancer drug responses, we screened a library of oncology compounds in cell lines with high endogenous PPFIA1 expression. The compounds with the highest differential responses between high PPFIA1‐expressing and silenced cells across cell lines were inhibitors targeting mitogen‐activated protein kinase kinase (MEK)/extracellular signal‐regulated kinases (ERK) signaling. KRAS proto‐oncogene, GTPase (KRAS)‐mutated MDA‐MB‐231 cells were more resistant to trametinib upon PPFIA1 knockdown compared with control cells. In contrast, liprin‐α1‐depleted HNSCC cells with low RAS activity showed a context‐dependent response to MEK/ERK inhibitors. Importantly, we showed that liprin‐α1 depletion leads to increased p‐ERK1/2 levels in all our studied cell lines independent of KRAS mutational status, suggesting a role of liprin‐α1 in the regulation of MAPK oncogenic signaling. Furthermore, liprin‐α1 depletion led to more pronounced redistribution of RAS proteins to the cell membrane. Our data suggest that liprin‐α1 is an important contributor to oncogenic RAS/MAPK signaling, and the status of liprin‐α1 may assist in predicting drug responses in cancer cells in a context‐dependent manner. [ABSTRACT FROM AUTHOR]

The development of robotic combine for rice harvesting has garnered worldwide attention in recent years. The robotic combine is capable of running along a designated path; however, it still requires human operator supervision due to the lack of object detection sensors for safety purposes. To achieve a fully unmanned robotic combine, a real‐time paddy field object detection method is necessary. Typically, all paddy field objects are detected individually using multiple algorithms and sensors, which significantly increases the complexity and cost of the detection process. In this study, the deep learning (DL) based semantic segmentation (SS) method was employed to detect all paddy field objects simultaneously using only an RGB camera. Considering the environment of the paddy field, a new SS model called "The Robotic Combine Network (TRCNet)" was specifically designed for the robotic combine. And four state‐of‐the‐art lightweight convolutional neural networks were applied as the backbones of the TRCNet. To achieve real‐time detection, TensorRT (NVIDIA) was utilized for speeding up the prediction process. All models were trained and evaluated using paddy field images captured during the robotic combine's harvesting process. The results showed that the TRCNet can successfully detect all paddy field objects. The mean intersection over union, and frames per second (FPS) of the best two SS models were 0.823, 47.48, and 0.834, 32.44, respectively. The FPS values were obtained after speed acceleration and tested with an image size of 640 × 480 pixels on an embedded processor (Jetson TX2), enabling real‐time object detection in paddy fields for the robotic combine. [ABSTRACT FROM AUTHOR]

Objectives: This study validated the Japanese version of the Attention‐Deficit/Hyperactivity Disorder‐Rating Scale‐5 (ADHD‐RS‐5) and the Disruptive Behavior Disorders Rating Scale. We extended the ADHD‐RS‐5 by adding the oppositional defiant disorder and conduct disorder subscales to compare the two rating scales psychometrically. Methods: We examined the internal consistency, test‐retest reliability, construct validity and criterion validity of the two rating scales in 135 Japanese outpatients aged 6–18 years. Results: The internal consistency and test‐retest reliability were good for all the subscales of the two rating scales except for the conduct disorder subscale of the ADHD‐RS‐5 extended. Good construct validity was revealed by expected correlational patterns between subscales from the two rating scales and the Children Behavior Checklist. The criterion validity was good for all the subscales of the two rating scales rated by parents, while teacher‐ratings revealed substantially lower predictive ability for all the subscales. Agreement between parent‐ and teacher‐ratings of the two rating scales was generally moderate and using predictive ratings alone of both ratings showed the best predictive ability among the integration methods examined. Conclusion: The two rating scales have sound psychometric properties and will aid in screening and severity assessment of externalizing disorders in Japanese clinical settings. [ABSTRACT FROM AUTHOR]

Aim: Antiseptics used at surgical sites are vital to preventing surgical site infections (SSI). In this study, a comparative investigation of the novel antiseptics olanexidine gluconate (OG) and povidone‐iodine (PI) was conducted to determine whether OG is more effective than PI against SSI after gastrointestinal surgery. Methods: This prospective, randomized, single‐blind, interventional, single‐center study was conducted between August 2018 and February 2021. Patients scheduled for large‐scale gastrointestinal surgeries were randomized into two groups and administered OG (OG group) or PI (PI group) as preoperative antiseptics. The primary endpoint was the SSI occurrence rate within 30 days after surgery. Results: In total, 525 patients were enrolled in this study, of whom 256 and 254 were in the OG and PI groups, respectively. The total SSI occurrence rate in the OG group (10.8%; n = 26) and the PI group (13.0%; n = 33) was not significantly different (p = 0.335). The occurrence rate of superficial incisional SSI and organ/space SSI did not significantly differ between the groups; however, that of deep incisional SSI showed a significant difference, with 0.4% (n = 1) in the OG group and 4.3% (n = 11) in the PI group (p = 0.003). Conclusion: OG, as a preoperative skin antiseptic, did not reduce the occurrence rate of total SSI. However, deep incisional SSI may be reduced using OG. [ABSTRACT FROM AUTHOR]

Aim: When administering tacrolimus, therapeutic drug monitoring is recommended because nephrotoxicity, an adverse event, occurs at supra‐therapeutic whole‐blood concentrations of tacrolimus. However, some patients exhibit nephrotoxicity even at the recommended concentrations, therefore establishing a therapeutic range of tacrolimus concentration for the individual patient is necessary to avoid nephrotoxicity. This study aimed to develop a model for individualized prediction of nephrotoxicity in patients administered tacrolimus. Methods: We collected data, such as laboratory test data at tacrolimus initiation, concomitant drugs and tacrolimus whole‐blood concentration, from medical records of patients who received oral tacrolimus. Nephrotoxicity was defined as an increase in serum creatinine levels within 60 days of tacrolimus initiation. We built 13 prediction models based on different machine learning algorithms: logistic regression, support vector machine, gradient‐boosting trees, random forest and neural networks. The best performing model was compared with the conventional model, which classifies patients according to the tacrolimus concentration alone. Results: Data from 163 and 41 patients were used to construct models and evaluate the best performing one, respectively. Most of the patients were diagnosed with inflammatory or autoimmune diseases. The best performing model was built using a support vector machine; it showed a high F2 score of 0.750 and outperformed the conventional model (0.500). Conclusions: A machine learning model to predict nephrotoxicity in patients during tacrolimus treatment was developed using tacrolimus whole‐blood concentration and other patient data. This model could potentially assist in identifying high‐risk patients who require individualized target therapeutic concentrations of tacrolimus prior to treatment initiation to prevent nephrotoxicity. [ABSTRACT FROM AUTHOR]