Search

Background and Objectives: The impact of preinjury anticoagulation on coagulation parameters over time after traumatic brain injury (TBI) has remained unclear. Based on the hypothesis that preinjury anticoagulation significantly influences the progression and persistence of TBI-induced coagulopathy, we retrospectively examined the association of preinjury anticoagulation with various coagulation parameters during the first 24 hours postinjury in 5 periods., Methods: Data from the Japanese registry of patients with TBI aged ≥65 years admitted between 2019 and 2021 were used. Time since injury was classified into 5 categories through a graphical analysis of coagulation parameters. We examined the association between preinjury anticoagulation and the platelet count, prothrombin time-international normalized ratio (PT-INR), activated partial thromboplastin time (APTT), D-dimer level, and fibrinogen level during each period by analysis of covariance using 10 clinical factors as confounding factors., Results: Data from 545 patients and 795 blood tests were analyzed. The patients' mean age was 78.9 years, and 87 (16%) received anticoagulation therapy. The preinjury anticoagulation group had significantly greater Rotterdam computed tomography scores and poorer outcomes at discharge than the control group, with significantly lower D-dimer levels and higher fibrinogen levels. Analysis of covariance revealed significant associations between the D-dimer level and preinjury anticoagulation within 2 to 24 hours postinjury, APTT and preinjury anticoagulation within 1 to 24 hours, and PT-INR and preinjury anticoagulation throughout all periods up to 24 hours postinjury., Conclusion: Despite more severe TBI signs and poorer outcomes, the preinjury anticoagulation group had significantly lower D-dimer levels, especially within 2 to 24 hours postinjury. Thus, D-dimer levels during this period may not reliably represent TBI severity in patients receiving anticoagulation therapy before injury. Preinjury anticoagulation was also associated with an elevated PT-INR and prolonged APTT from early to 24 hours postinjury, highlighting the importance of aggressive anticoagulant reversal early after injury., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the Congress of Neurological Surgeons.)

Objective: To examine the association between adjuvant chemotherapy and survival outcomes in patients with stage I uterine leiomyosarcoma (uLMS)., Methods: This comprehensive systematic review and meta-analysis through December 31, 2023 (PROSPERO registration number: CRD42024504776) investigated studies that examined survival outcomes in patients with stage I uLMS using 4 public search engines (PubMed, Scopus, Web of Science, and the Cochrane Central Register of Controlled Trials). Two investigators searched the studies independently, and survival outcomes (overall survival [OS] and disease-free survival [DFS]) were compared between the adjuvant chemotherapy and observation groups. Utilization rate of adjuvant chemotherapy and the regimens used were also assessed. Kaplan-Meier survival curves in the two treatment groups were evaluated using ImageJ software., Results: From 1988 to 2022, 16 eligible studies including a total of 5690 patients met the inclusion criteria and evaluated the effect of adjuvant chemotherapy on survival outcomes in patients with stage I uLMS. Adjuvant chemotherapy was utilized in 38.5 % of patients (range, 14.8 % to 70.0 %). Eight studies from 2017 to 2022 compared the survival outcomes between adjuvant chemotherapy and observation. OS was comparable between the two groups in both unadjusted (n = 6, hazard ratio [HR] 1.02, 95 % confidence interval [CI] 0.77-1.35, P = 0.88) and adjusted (n = 4, HR 0.90, 95 %CI 0.56-1.43, P = 0.65) pooled analyses. DFS was also similar between adjuvant chemotherapy and observation in both unadjusted (n = 4, HR 0.78, 95 %CI 0.53-1.13, P = 0.18) and adjusted (n = 2, HR 1.14, 95 %CI 0.67-1.94, P = 0.64) pooled analyses. Adjuvant chemotherapy regimens utilized included doxorubicin, ifosfamide, cisplatin, gemcitabine, and docetaxel as monotherapies or combination therapies., Conclusions: In this contemporaneous systematic review and meta-analysis, less than 40 % of patients received adjuvant chemotherapy for stage I uLMS and adjuvant chemotherapy which was not associated with improved survival. These results support the current National Comprehensive Cancer Network clinical practice guidelines that recommends de-escalating adjuvant chemotherapy in stage I uLMS after complete resection., Competing Interests: Declaration of competing interest Research funding, MSD (S.M.); consultant, Cardiff Oncology, Nutcracker, participation in the Steering Committee for the Global Coalition of Adaptive Research (L.D.R.); consultant, research grant, Merck, royalties, UpToDate, honorarium, American College of Obstetrics and Gynecology (J.D.W.); none for others., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Glioblastomas (GBMs) are the most aggressive types of central nervous system tumors. Although certain genomic alterations have been identified as prognostic biomarkers of GBMs, the histomorphological features that predict their prognosis remain elusive. In this study, following an integrative diagnosis of 227 GBMs based on the 2021 World Health Organization classification system, the cases were histologically fractionated by cellular variations and abundance to evaluate the relationship between cellular heterogeneity and prognosis in combination with O-6-methylguanine-DNA methyltransferase gene promoter methylation (mMGMTp) status. GBMs comprised four major cell types: astrocytic, pleomorphic, gemistocytic, and rhabdoid cells. t-distributed stochastic neighbor embedding analysis using the histological abundance of heterogeneous cell types identified two distinct groups with significantly different prognoses. In individual cell component analysis, the abundance of gemistocytes showed a significantly favorable prognosis but confounding to mMGMTp status. Conversely, the abundance of epithelioid cells was correlated with the unfavorable prognosis. Linear model analysis showed the favorable prognostic utility of quantifying gemistocytic and epithelioid cells, independent of mMGMTp. The evaluation of GBM cell histomorphological heterogeneity is more effective for prognosis prediction in combination with mMGMTp analysis, indicating that histomorphological analysis is a practical and useful prognostication tool in an integrative diagnosis of GBMs., (© 2024. The Author(s).)

In African American adults, the strongest genetic predictor of pneumonia appears to be the A allele of rs334, a variant in the β-globin gene which in homozygous form causes sickle cell disease (SCD). No comparable studies have been done in African American children. We performed genome-wide association analyses of 482 African American children with documented pneumonia and 2048 African American controls using genotypes imputed from two reference panels: 1000 Genomes (1KG) (which contains rs334) and TOPMed (does not contain rs334). Using 1KG imputed genotypes, the most significant variant was rs334 (A allele (OR = 2.76 (2.21-3.74), p=5.9x10 -19 ); using TOPMed imputed genotypes the most significant variant was rs2226952, found in the β-globin locus control region (G allele (OR =2.14 (1.78-2.57), p = 5.1x10 -16 ). After conditioning on rs334, the most strongly associated variant in the β-globin locus was rs33930165, (allele T, 1KG: OR=4.09 (2.29-7.29), p=1.7x10 -6 ; TOPMed: OR=3.58 (2.18-5.90), p=4.7x10 -7 ), which as a compound heterozygote with rs334 A allele can cause SCD. To compare the power of different sample sets we developed a way to estimate the power of sample sets with different sample sizes, genotype arrays and imputation platforms. Our results suggest that in African American children the strongest genetic determinants of pneumonia are those that increase the risk of SCD., (Copyright © 2024. Published by Elsevier Inc.)

Background: The prevalence of wild-type transthyretin (ATTR) amyloidosis is increasing with advancements in diagnostic techniques and growing awareness of the disease worldwide. 99m Tc-labeled pyrophosphate ( 99m Tc-PYP) scintigraphy exhibits high performance in diagnosing ATTR cardiac amyloidosis. This study aimed to validate the characteristics of patients with positive 99m Tc-PYP scintigraphy results in a multicenter setting to provide more accurate case selection criteria., Methods and Results: In total, 180 patients with suspected ATTR amyloidosis underwent 99m Tc-PYP scintigraphy in participating institutions in Japan between January 2018 and July 2022. Of 135 patients included in the analysis, 62 were 99m Tc-PYP-positive. Logistic regression analysis was performed, and the following five factors were adopted to create a scoring system, with each weighted according to its odds ratio value; 1 point was scored for the absence of hypertension, existence of peripheral entrapment neuropathy (carpal tunnel syndrome or spinal canal stenosis), conduction disturbance (the presence of QRS complex ≥120 ms, first-degree atrioventricular block, higher degree of atrioventricular block, or presence of pacemaker implantation), and left ventricular hypertrophy and 2 points for troponin I/T ≥ 0.06 ng/mL. 99m Tc-PYP scintigraphy positivity rate in the 0-point group was 0 %, whereas that in the 6-point group was 100 %. The area under the curve of the criteria was 0.820 (95 % confidence interval, 0.752-0.888; P < 0.001)., Conclusions: The combination of clinical information, which is easily available in local clinics, can provide accurate pretest prediction of positive 99m Tc-PYP scintigraphy results. This will help clinicians to make an early diagnosis of ATTR amyloidosis., Competing Interests: Declaration of competing interest Yuya Matsue received an honorarium from Otsuka Pharmaceutical Co., Novartis Pharma K.K., Bayer Inc., and AstraZeneca, and a collaborative research grant from Pfizer Japan Inc., Otsuka Pharmaceutical Co., EN Otsuka Pharmaceutical Co., Ltd., and Nippon Boehringer Ingelheim Co., Ltd. Hidekazu Tanaka received remuneration from AstraZeneca plc, Ono Pharmaceutical Company, Limited. Pfizer Inc., Otsuka Pharmaceutical Co., Ltd., Daiichi Sankyo Company, Limited, Eli Lilly and Company, Boehringer Ingelheim GmbH, Abbott Japan LLC, and Novartis International AG., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Objective: Healthy dietary patterns have been linked to lower levels of chronic inflammation. The present study aimed to investigate the associations between food group intakes and high-sensitivity C-reactive protein (hsCRP) among community-dwelling adults., Design: Cross-sectional., Setting: Three areas in Japan (Shiga, Fukuoka, or Kyushu and Okinawa)., Participants: The present analysis included 13 648 participants (5126 males and 8522 females; age range, 35-69 years) who had been enrolled in the baseline survey of the Japan Multi-Institutional Collaborative Cohort Study. Food group intakes were estimated using a FFQ. Multiple linear regression was used to examine associations between the quartiles of each energy-adjusted food group intake and log-transformed hsCRP., Results: The following concentration ratios of hsCRP after comparing the highest and lowest quartiles of food group intake were significant: in males, 1·12 (95 % CI 1·02, 1·22) for processed meat, 1·13 (95 % CI 1·03, 1·24) for fish and 0·83 (95 % CI 0·76, 0·90) for nuts; in females, 0·89 (95 % CI 0·81, 0·97) for bread, 1·11 (95 % CI 1·03, 1·19) for processed meat, 0·86 (95 % CI 0·80, 0·92) for vegetables, 1·19 (95 % CI 1·11, 1·29) for fruit, 0·90 (95 % CI 0·84, 0·97) for nuts and 0·88 (95 % CI 0·82, 0·95) for green tea., Conclusions: Processed meat and nut intakes were associated with higher and lower hsCRP levels, respectively, in both sexes. However, for several food groups, including fish and fruit, previous findings from dietary pattern analyses were not supported by the present analyses at the food group level.

Background: The iPocc trial, a randomized, global phase 3 study that compared intraperitoneal (IP) and intravenous (IV) carboplatin with dose-dense paclitaxel chemotherapy in epithelial ovarian cancer (EOC) patients, demonstrated improved progression-free survival in patients who received IP chemotherapy. The present study aimed to investigate the role of preexisting tumor immunity in the clinical outcomes of patients receiving IP chemotherapy., Methods: This study involved analyzing patient data from the iPocc trial, selectively of those whose tumor specimens were preserved at the time of primary surgery. A total of 116 cases ((IP; n = 59), (IV; n = 57)) were subjected to microarray analysis. Single-sample gene set enrichment analyses were performed to evaluate the tumor immune microenvironment., Results: Patients with enhanced tumor infiltration of T cells, natural killer (NK) cells, and cytotoxic lymphocytes in the IP group had a longer overall survival (OS) than those in the IV group, but not in the group with low infiltration. IP therapy improved the OS of patients with high expression of immune-related genes such as CD8A and FOXP3. In patients' subdivided into "immune Hot" and "immune Cold" groups based on hierarchical clustering analysis using four parameters representing "Innate immunity," "T cells," "IFNG response" and "Inhibitory molecules," IP therapy significantly improved prognosis in the "immune Hot" group, but not in the "immune Cold" group compared to that of IV therapy., Conclusions: IP chemotherapy enhances the survival rates of patients with EOC with an immune-Hot phenotype in the tumor microenvironment prior to treatment. (Japan Registry of Clinical Trials number, jRCTs031180141.)., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Gout is a chronic disease that is caused by an innate immune response to deposited monosodium urate crystals in the setting of hyperuricemia. Here, we provide insights into the molecular mechanism of the poorly understood inflammatory component of gout from a genome-wide association study (GWAS) of 2.6 million people, including 120,295 people with prevalent gout. We detected 377 loci and 410 genetically independent signals (149 previously unreported loci in urate and gout). An additional 65 loci with signals in urate (from a GWAS of 630,117 individuals) but not gout were identified. A prioritization scheme identified candidate genes in the inflammatory process of gout, including genes involved in epigenetic remodeling, cell osmolarity and regulation of NOD-like receptor protein 3 (NLRP3) inflammasome activity. Mendelian randomization analysis provided evidence for a causal role of clonal hematopoiesis of indeterminate potential in gout. Our study identifies candidate genes and molecular processes in the inflammatory pathogenesis of gout suitable for follow-up studies., (© 2024. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Tosufloxacin tosilate is classified as a new quinolone antibacterial agent, which has been reported to cause crystal nephropathy. However, the origin of these crystal deposits has not yet been elucidated. We encountered a case of renal failure that progressed slowly owing to crystal-forming interstitial nephritis after long-term exposure to tosufloxacin. Mass spectrometry of the renal specimens revealed that tosufloxacin was deposited in the kidneys. The patient's renal function improved slowly with the withdrawal of tosufloxacin and steroid therapy. This is the first case to demonstrate the presence of crystal deposits consisting of tosufloxacin.

Synucleinopathies, including Parkinson's disease, dementia with Lewy bodies, and multiple system atrophy, are triggered by α-synuclein aggregation, triggering progressive neurodegeneration. However, the intracellular α-synuclein aggregation mechanism remains unclear. Herein, we demonstrate that RNA G-quadruplex assembly forms scaffolds for α-synuclein aggregation, contributing to neurodegeneration. Purified α-synuclein binds RNA G-quadruplexes directly through the N terminus. RNA G-quadruplexes undergo Ca 2+ -induced phase separation and assembly, accelerating α-synuclein sol-gel phase transition. In α-synuclein preformed fibril-treated neurons, RNA G-quadruplex assembly comprising synaptic mRNAs co-aggregates with α-synuclein upon excess cytoplasmic Ca 2+ influx, eliciting synaptic dysfunction. Forced RNA G-quadruplex assembly using an optogenetic approach evokes α-synuclein aggregation, causing neuronal dysfunction and neurodegeneration. The administration of 5-aminolevulinic acid, a protoporphyrin IX prodrug, prevents RNA G-quadruplex phase separation, thereby attenuating α-synuclein aggregation, neurodegeneration, and progressive motor deficits in α-synuclein preformed fibril-injected synucleinopathic mice. Therefore, Ca 2+ influx-induced RNA G-quadruplex assembly accelerates α-synuclein phase transition and aggregation, potentially contributing to synucleinopathies., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Purpose: Post-operative meniscal cyst formation occurs following all-inside device meniscal repair. This study aimed to compare the incidence of cysts in patients who underwent meniscal repair with and without all-inside suture devices., Methods: This retrospective study included 227 knees that underwent meniscal repair between 2021 and 2022. The incidence of post-operative meniscal cysts was compared between patients who underwent repair using an all-inside suture anchor device (Group SA) and those who did not use an anchor (Group NA), based on post-operative magnetic resonance imaging (MRI) findings. Risk factors, such as the number of anchors used, were investigated. Using a subgroup analysis, the incidence of meniscal cysts based on the type of device used was investigated., Results: Groups SA and NA comprised 125 and 102 knees, respectively. Group SA had 11 cases of cysts (9% incidence), whereas Group NA had 7 cases (7% incidence), and no statistically significant difference was observed ( p  = 0.63). Symptomatic cysts were observed in two patients (1.6%) in Group SA, whereas none was observed in Group NA (0%); the difference was not significant ( p  = 0.50). Factors such as the number of anchors and sutures used and MRI timing were not identified as risk factors. Cyst incidence varied according to anchor type: Stryker AIR+ (4 out of 55, 7%), Smith & Nephew Fast-Fix 360 (7 out of 56, 13%) and Arthrex Fiber Stitch (0 out of 26, 0%), with no significant difference found ( p  = 0.14)., Conclusion: The incidence of cysts in patients undergoing meniscal repair with an all-inside suture anchor device was 9%, showing no significant difference compared with Group NA. Cyst incidence was not affected by device type., Level of Evidence: Level III, retrospective comparative study., Competing Interests: The authors declare no conflict of interest., (© 2024 The Author(s). Journal of Experimental Orthopaedics published by John Wiley & Sons Ltd on behalf of European Society of Sports Traumatology, Knee Surgery and Arthroscopy.)

Observational and cohort studies using large databases have made important contributions to gynecologic oncology. Knowledge of the advantages and potential limitations of commonly used databases benefits both readers and reviewers. In this review, researchers familiar with National Cancer Database (NCDB), Surveillance, Epidemiology, and End Results Program (SEER), SEER-Medicare, MarketScan, Healthcare Cost and Utilization Project (HCUP), National Surgical Quality Improvement Program (NSQIP), and Premier, describe each database, its included data, access, management, storage, highlights, and limitations. A better understanding of these commonly used datasets can help readers, reviewers, and researchers to more effectively interpret and apply study results, evaluate new research studies, and develop compelling and practice-changing research., Competing Interests: Competing interests: None declared., (© IGCS and ESGO 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: Given limited real-world practice data evaluating the National Comprehensive Cancer Network clinical practice guidelines for possible post-operative chemotherapy omission as a treatment option for patients with stage IC grade 1 endometrioid ovarian carcinoma, this population-based study examined the association between post-operative chemotherapy and overall survival in this tumor group., Methods: The National Cancer Institute's Surveillance, Epidemiology, and End Results program was retrospectively queried. The study population was 1207 patients with stage IC grade 1-3 endometrioid ovarian carcinoma who received primary cancer-directed surgery from 2007 to 2020. Overall survival was assessed with multivariable Cox proportional hazard regression model., Results: The median age was 52, 54, and 55 years for grade 1, 2, and 3 groups, respectively (p=0.02). Grade 1 and 2 tumors were more common than grade 3 tumors (n=508 (42.1%), n=493 (40.8%), and n=206 (17.1%), respectively). Chemotherapy use rate for grade 1 tumors was lower compared with grade 2-3 tumors (67.9%, 76.5%, and 78.6%, respectively, p<0.001). When nodal evaluation was performed for grade 1 tumors, among patients who did not receive post-operative chemotherapy and among those who did, 5-year overall survival rate exceeded 90% (93.3% and 96.0%, respectively), with statistically non-significant hazard estimates (adjusted hazard ratio (aHR) 1.54, 95% CI 0.63 to 3.73). In contrast, post-operative chemotherapy omission for patients who did not undergo nodal evaluation was associated with decreased overall survival (5-year rates 82.3% vs 96.0%, aHR 5.41, 95% CI 1.95 to 15.06). Results were similar for node-evaluated grade 2 tumors (5-year overall survival rates, 94.6% and 94.4% for node-evaluated post-operative chemotherapy omission and administration, respectively), but not in grade 3 tumors., Conclusion: The results of this population-based study may partially support the current clinical practice guidelines for post-operative chemotherapy omission as a possible option for patients with stage IC grade 1 endometrioid adenocarcinoma of the ovary for those who had lymph node evaluation. Observed data were also supportive for node-evaluated grade 2 tumors, warranting further evaluation., Competing Interests: Competing interests: Consultant, AstraZeneca, CooperSurgical, Immunogen, and KLS Martin (MK); research grant, Merck, royalties, UpToDate, honorarium, American College of Obstetrics and Gynecology (JDW); consultant, Cardiff Oncology, Nutcracker, participation in the Steering Committee for the Global Coalition of Adaptive Research (LDR); none for others., (© IGCS and ESGO 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Emerging evidence suggests a link between salivary metabolite changes and neurodegenerative dementia, with antimicrobial peptides (AMPs) implicated in its pathogenesis., Objective: We investigated the effects of a clinical oral rehabilitation programme tailored for dementia patients on salivary flow rate, AMP levels and oral health-related quality of life (OHRQoL)., Methods: Eligible patients were randomly assigned to either the experimental group (EG; n = 28) or the control group (CG; n = 27). Both groups received a leaflet on oral health. In addition, the EG received an oral care intervention that included individual lessons on oral muscle exercises and oral self-care practices. Saliva samples and OHRQoL data were collected at baseline and follow-up visits. Generalised estimating equation models were used to analyse the changes over time., Results: At the 3-month follow-up, EG showed significantly lower histatin 5 (HTN-5) levels (β = -0.08; effect size [ES] = 0.72) than CG. At 6 months, EG exhibited improved salivary flow rate (β = 0.89; ES = 0.89) and OHRQoL (β = 6.99; ES = 1.31) compared to CG. Changes in salivary flow rate (β = 4.03), HTN-5 level (β = -0.78) and beta-defensin 2 level (BD-2) (β = -0.91) at 3 months predicted improved OHRQoL at 6 months (all p < 0.05)., Conclusions: Our clinical oral rehabilitation programme reduced the level of salivary HTN-5, increased salivary flow rate and enhanced OHRQoL in dementia patients. Furthermore, changes in salivary flow rate, HTN-5 level and BD-2 level were associated with improvements in patients' OHRQoL., (© 2024 John Wiley & Sons Ltd.)

Objectives: To evaluate changes in the age at menarche in Asian populations., Study Design: Retrospective cohort study., Methods: We included 548,830 women from six countries in Asia. The data were sourced from 20 cohorts participating in the Asia Cohort Consortium (ACC) and two additional cohort studies: Japan Multi-institutional Collaborative Cohorts (J-MICC), and Japan Nurse Health Study (JNHS) with data on age at menarche. Joinpoint regression was used to evaluate changes in age at menarche by birth year and by country., Results: The study includes data from cohorts in six Asian countries namely, China, Iran, Japan, Korea, Malaysia and Singapore. Birth cohorts ranged from 1873 to 1995. The mean age of menarche was 14.0 years with a standard deviation (SD) of 1.4 years, ranged from 12.6 to 15.5 years. Over 100 years age at menarche showed an overall decrease in all six countries. China showed a mixed pattern of decrease, increase, and subsequent decrease from 1926 to 1960. Iran and Malaysia experienced a sharp decline between about 1985 and 1990, with APC values of -4.48 and -1.24, respectively, while Japan, South Korea, and Singapore exhibited a nearly linear decline since the 1980s, notably with an APC of -3.41 in Singapore from 1993 to 1995., Conclusions: Overall, we observed a declining age at menarche, while the pace of the change differed by country. Additional long-term observation is needed to examine the contributing factors of differences in trend across Asian countries. The study could serve as a tool to strengthen global health campaigns., (Copyright © 2024 The Royal Society for Public Health. Published by Elsevier Ltd. All rights reserved.)

Family history of lung cancer (FHLC) has been widely studied but most prospective cohort studies have primarily been conducted in non-Asian countries. We assessed the association between FHLC with risk of lung cancer (LC) incidence and mortality in a population of East Asian individuals. A total of 478,354 participants from 11 population-based cohorts in the Asia Cohort Consortium were included. A Cox proportional hazards regression model was used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). A total of 7,785 LC incident cases were identified. FHLC (any LC subtype) was associated with an increased risk of LC incidence (HR = 1.45, 95% CI = 1.30-1.63). The positive association was observed in men and women (HR = 1.44, 95% CI = 1.26-1.66 in men; HR = 1.47, 95% CI = 1.22-1.79 in women), and in both never-smokers and ever-smokers (HR = 1.43, 95% CI = 1.18-1.73 in never-smokers; HR = 1.46, 95% CI =1.27-1.67 in ever-smokers). FHLC was associated with an increased risk of lung adenocarcinoma (HR = 1.63, 95% CI: 1.36-1. 94), squamous cell carcinoma (HR = 1.88, 95% CI: 1.46-2.44), and other non-small cell LC (HR = 1.94, 95% CI: 1.02-3.68). However, we found no evidence of significant effect modification by sex, smoking status, and ethnic groups. In conclusion, FHLC was associated with increased risk of LC incidence and mortality, and the associations remained consistent regardless of sex, smoking status and ethnic groups among the East Asian population., (© 2024 The Author(s). International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC.)

We identified two gall-inducing wasp species infesting eucalypts leaves, including an undescribed species, Ophelimus cracens sp. nov., and Epichrysocharis burwelli , which is a new record for Taiwan. The major hosts of O. cracens were Eucalyptus grandis , Eu. urophylla , and Eu. camaldulensis (Myrtaceae) . We observed failed galls of O. cracens at an early stage on Eu. amplifolia and Corymbia maculata . All O. cracens adults discovered on infected leaves were females, and four parasitoid species were identified in samples collected from two cities, three counties, and four municipalities across Taiwan. Epichrysocharis burwelli was exclusively found on C. citriodora in Hsinchu, Nantou, and Tainan Cities. This marks the first record of Ep. burwelli in Asia, accompanied by the identification of one parasitoid species. The adult longevity of adults which emerged from their major hosts, when provided with honey-water solution, was 5.5 days for O. cracens and 5.7 days for Ep. burwelli . Recognizing the potential damage by these wasps on Eucalyptus production areas in the absence of parasitoids, further investigations of their biology and control are warranted.

The current study exploited cheese whey supernatant (CWS) as a renewable resource for polyhydroxyalkanoates (PHAs) formation. Structure identification and investigating the influence of lipid membranes' chemistry on PHA structuration were detailed. Approximately 66 bacterial isolates from dairy products companies in Egypt were screened for PHA production, and the bacterial isolate AZU-A5, identified as Bacillus licheniformis strain AZU-A5, showed the highest production PHA 0.93 g L -1 ) using whey lactose. The highest PHA rate in the individual design was 1.59 g L -1 with a recovery yield of 33.08% (w w -1 ), while the production rate in the statistical design reached 1.75 g L -1 PHA and 51.60% PHA content. Structurally, the PHA was identified as polyhydroxy-3R-butyrate (R-PH3B). The fibrous texture by SEM highlighted the self-assembly of PHB. The CD analysis of the PHA films suggested favorable hydrophobic interactions between lipids and PHB. Higher lipid contents not only caused a decrement in the CD signal of PHB but also bathochromic effects occurred. The chain length of lipids exerted high impacts on interactions (CD) and structuration of PHB (Δλ). The unsaturation showed little influence on CD and negligible effect on Δλ, while the head group exerted no effect on CD with a considerable impact on Δλ., (© 2024 The Author(s). Chirality published by Wiley Periodicals LLC.)

α-Synuclein (αS) causes Parkinson's disease due to the structural alteration into amyloid fibrils that form after the interaction with synaptic membranes in neurons. To understand the alternation mechanism, the effect of salt (NaCl) on the interaction of αS with synaptic mimic membrane was characterized at the molecular level because salt triggered the amyloid fibril formation. The membrane-bound conformation (or the initial conformation before fibrillation) showed that NaCl decreased the number of helical structures and Tyr residues interacting with the membrane surface compared to when NaCl was absent, implying an increase in solvent-exposed regions. The N-terminal region of αS interacted with the membrane, forming the helical structures regardless of NaCl, while the C-terminal region formed a random structure with weak membrane interaction, but NaCl inhibited the interaction of its hydrophobic area, suggesting that salt promoted amyloid fibril formations by exposing the hydrophobic C-terminal region, which can intermolecularly interact with free αS.

Background: Second primary esophageal cancer often develops in patients with head and neck cancer, and esophagectomy in patients with a history of total pharyngolaryngectomy (TPL) is challenging. However, the clinical outcomes of these patients have yet to be examined in a multicenter setting., Methods: We evaluated the surgical outcomes of a nationwide cohort of 62 patients who underwent esophagectomy for esophageal cancer with a history of TPL., Results: Ivor-Lewis and McKeown esophagectomies were performed in 32 (51.6%) and 30 (48.4%) patients, respectively. Postoperatively, 23 patients (37.1%) developed severe complications, and 7 patients (11.3%) required reoperation within 30 days. Pneumonia and anastomotic leakage occurred in 13 (21.0%) and 16 (25.8%) patients, respectively. Anastomotic leakage occurred more frequently in the McKeown group than in the Ivor-Lewis group (46.7% vs. 6.2%, P < 0.001). The adjusted odds ratio for anastomotic leakage in the McKeown group was 9.64 (95% confidence intervals (CI), 2.11-70.82, P = 0.008). Meanwhile, the 5-year overall survival rates were comparable between the groups (41.8% for Ivor-Lewis and 42.7% for McKeown), and the adjusted hazard ratio of overall survival was 1.44 (95% CI, 0.64-3.29; P = 0.381; Ivor-Lewis as the reference)., Conclusions: In our cohort, anastomotic leakage occurred more frequently after McKeown than Ivor-Lewis esophagectomy, and almost half of patients in the McKeown group experienced leakage. Ivor-Lewis esophagectomy is preferred for decreasing anastomotic leakage when oncologically and technically feasible., (© 2024. The Author(s) under exclusive licence to The Japan Esophageal Society.)

This study aimed to investigate the effect of diagnosis and treatment of chronic endometritis (CE) on the outcome of assisted reproductive technology (ART) with or without repeated implantation failure (RIF). This retrospective analysis included patients who underwent pathological examination for diagnosis of CE at Yamagata University Hospital. The examination was performed for all patients planned for ART with or without RIF. Patients who were examined within 6 months of the first oocyte retrieval or embryo transfer were included. We counted the number of CD138-positive cells within the endometrial stroma in patients' specimens and analyzed the patients' clinical information. Clinical rates of pregnancy and implantation were determined. A total of 80 women met the inclusion criteria: 13 CE-negative patients (17.3%) and 67 CE-positive patients (83.7%). A significant decrease was noted in the CD138-positive cell count between the first biopsy and second biopsy after CE treatment (p < 0.001). In addition, no significant differences were noted in ongoing pregnancy rates between the CE-negative patients and those who underwent CE treatment. The CD138-positive cell counts at first biopsy tended to be lower in each pregnancy group than in the non-pregnancy group. For patients planned to undergo ART, examination for diagnosis of CE with or without RIF could be considered. Pathological CD138-positive cell counts were considered useful for CE diagnosis and treatment decision-making. The study findings suggest the efficacy of antimicrobial agents in CE treatment, contributing to improved pregnancy outcomes., (© 2024. The Author(s).)

Introduction: Intimate partner violence (IPV) is the leading cause of death in pregnant women. Although it can be difficult to identify patients experiencing IPV, injuries to the head, neck, or face due to an assault are known to correlate with intentional injury. The objective of this study is to assess the contemporary burden of IPV in pregnancy and describe the patient characteristics., Methods: The National Inpatient Sample was queried for all pregnant women between January 2016 and December 2019. Patients were divided into two groups: suspected IPV (SIPV) and no-SIPV groups. We defined SIPV as any pregnant patient with an identified head, neck, or face injuries categorized as intentional assault. Multivariable logistic regression analysis was performed to assess the association between SIPV and variables of interest., Results: A total of 28,540 pregnant patients presented with traumatic injuries with 530 (.02%) identified as SIPV. Suspected IPV patients were younger (25 vs 27 years, P = .012), more likely to be of Black race (46% vs 28%, P = .002), more likely to be in the lowest income quartile (51% vs 38%, P = .031), less likely to have private insurance (12% vs 34%, P < .001), and have higher rates of substance use disorder (35% vs 18%, P < .001). Black race and history of substance use disorder were associated with increased odds of SIPV-related injuries (odds ratio [OR]: 2.01, interquartile range [IQR]: 1.27-3.16, P = .003 and OR: 2.30, IQR 1.54-3.43, P < .001, respectively)., Conclusions: Our results suggest that there are significant racial and socioeconomic disparities in potential risk for IPV during pregnancy., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Purpose: Chordomas are malignant tumors that destroy bones, compress surrounding nerve tissues and exhibit phenotypes that recapitulate notochordal differentiation in the axial skeleton. Chordomas recur frequently, as they resist radio-chemotherapy and are difficult to completely resect, leading to repeated bone destruction and local expansion via unknown mechanisms. Here, using chordoma specimens and JHC7 chordoma cells, we asked whether chordoma cells possess bone-dissolving activity., Methods: CT imaging and histological analysis were performed to evaluate the structure and mineral density of chordoma-invaded bone and osteolytic marker expression. JHC7 cells were subjected to immunocytochemistry, imaging of cell fusion, calcium dynamics and acidic vacuoles, and bone lysis assays., Results: In patients, we found that the skull base invaded by chordoma was highly porous, showed low mineral density and contained brachyury-positive chordoma cells and conventional osteoclasts both expressing the osteolytic markers tartrate-resistant acid phosphatase (TRAP) and collagenases. JHC7 cells expressed TRAP and cathepsin K, became multinucleated via cell-cell fusion, showed spontaneous calcium oscillation, and were partly responsive to the osteoclastogenic cytokine RANKL. JHC7 cells exhibited large acidic vacuoles, and nonregulatory bone degradation without forming actin rings. Finally, bone-derived factors, calcium ions, TGF-β1, and IGF-1 enhanced JHC7 cell proliferation., Conclusion: In chordoma, we propose that in addition to conventional bone resorption by osteoclasts, chordoma cells possess bone-dissolving activity at the tumor-bone boundary. Furthermore, bone destruction and tumor expansion may occur in a positive feedback loop., (© 2024. The Author(s).)

This nationwide study retrospectively examined the center effect on allogeneic hematopoietic stem cell transplantation (allo-HSCT) for adult B-cell acute lymphoblastic leukemia. The cohort analyses were separated into Philadelphia chromosome (Ph)-positive and -negative cases. The patients were divided into low- and high-volume groups according to the number of allo-HSCTs at each facility. The primary endpoint was 5-year overall survival (OS). This study included 1156 low-volume and 1329 high-volume Ph-negative and 855 low-volume and 926 high-volume Ph-positive cases. In Ph-negative cases, 5-year OS was significantly higher in the high-volume centers at 52.7% (95% confidence interval [CI]: 49.9-55.5) versus 46.8% (95% CI: 43.8-49.7) for the low-volume centers (P < 0.01). Multivariate analysis identified high volume as a favorable prognostic factor (hazard ratio [HR]: 0.81 [95% CI: 0.72-0.92], P < 0.01). Subgroup analysis in Ph-negative cases revealed that the center effects were more evident in patients aged ≥40 years (HR: 0.72, 95% CI: 0.61-0.86, P < 0.01) and those receiving cord blood transplantation (HR: 0.62, 95% CI: 0.48-0.79, P < 0.01). In Ph-positive cases, no significant difference was observed between the high and low-volume centers for 5-year OS (59.5% [95% CI: 56.2-62.7] vs. 54.9% [95% CI: 51.3-58.3], P = 0.054). In multivariate analysis, center volume did not emerge as a significant prognostic indicator. This study showed center effects on survival in Ph-negative but not in Ph-positive cases, highlighting the heterogeneity of the center effect in allo-HSCT for B-cell acute lymphoblastic leukemia. Collaborative efforts among transplant centers and further validation are essential to improve outcomes., Competing Interests: Declaration of Competing Interest The authors declare no competing interests., (Copyright © 2024 International Society for Cell & Gene Therapy. Published by Elsevier Inc. All rights reserved.)

A set of arylazopyrazole-based inhibitors targeting the mitotic motor protein CENP-E was discovered through the chemical platform using the quantitative cyclization of 1,3-diketone intermediate with various hydrazines under mild conditions. Through this efficient platform, the structure-activity relationship pertaining to the pyrazole photoswitch in photoswitchable CENP-E inhibitors not only in vitro but also in cells was successfully clarified., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

This research identified a marine fungal isolate, Aspergillus sp. strain GAD7, which produces an acidic and sulfated extracellular polysaccharide (EPS) with notable anticoagulant and antioxidant properties. Six fungal strains from the Egyptian Mediterranean Sea were screened for EPS production, with Aspergillus sp. strain GAD7 (EPS-AG7) being the most potent, yielding ~5.19 ± 0.017 g/L. EPS-AG7 was characterized using UV-Vis and FTIR analyses, revealing high carbohydrate (87.5%) and sulfate (24%) contents. HPLC and GC-MS analyses determined that EPS-AG7 is a heterogeneous acidic polysaccharide with an average molecular weight (Mw¯) of ~7.34 × 10 3 Da, composed of mannose, glucose, arabinose, galacturonic acid, galactose, and lyxose in a molar ratio of 6.6:3.9:1.8:1.3:1.1:1.0, linked through α- and β-glycosidic linkages as confirmed by NMR analysis. EPS-AG7 adopted a triple helix-like conformation, as evidenced by UV-Vis (Congo Red experiment) and circular dichroism (CD) studies. This helical arrangement demonstrated stability under various experimental conditions, including concentration, ionic strength, temperature, and lipid interactions. EPS-AG7 exhibited significant anticoagulant activity, doubling blood coagulation time at a concentration of 3.0 mg/mL, and showed significant antioxidant activity, with scavenging activities reaching up to 85.90% and 58.64% in DPPH and ABTS + assays at 5.0 mg/mL, and EC50 values of 1.40 mg/mL and 3.80 mg/mL, respectively. These findings highlight the potential of EPS-AG7 for therapeutic applications due to its potent biological activities.

Background: Nonresectable gastric cancer develops rapidly; thus, monitoring disease progression especially in patients receiving nivolumab as late-line therapy is important. Biomarkers may facilitate the evaluation of nivolumab treatment response. Herein, we assessed the utility of serum-based inflammatory indicators for evaluating tumor response to nivolumab., Methods: This multicenter retrospective cohort study included 111 patients treated with nivolumab monotherapy for nonresectable advanced or recurrent gastric cancer from October 2017 to October 2021. We measured changes in the C-reactive protein (CRP)-to-albumin ratio (CAR), platelet-to-lymphocyte ratio (PLR), and neutrophil-to-lymphocyte ratio (NLR) in serum from baseline to after the fourth administration of nivolumab. Furthermore, we calculated the area under the receiver operating characteristic curves (AUC ROCs) for CAR, PLR, and NLR to identify the optimal cutoff values for treatment response. We also investigated the relationship between clinicopathologic factors and disease control (complete response, partial response, and stable disease) using the chi-squared test., Results: The overall response rate (complete and partial response) was 11.7%, and the disease control rate was 44.1%. The median overall survival (OS) was 14.0 (95% CI 10.7‒19.2) months, and the median progression-free survival (PFS) was 4.1 (95% CI 3.0‒5.9) months. The AUC ROCs for CAR, PLR, and NLR before nivolumab monotherapy for patients with progressive disease (PD) were 0.574 (95% CI, 0.461‒0.687), 0.528 (95% CI, 0.418‒0.637), and 0.511 (95% CI, 0.401‒0.620), respectively. The values for changes in CAR, PLR, and NLR were 0.766 (95% CI, 0.666‒0.865), 0.707 (95% CI, 0.607‒0.807), and 0.660 (95% CI 0.556‒0.765), respectively. The cutoff values for the treatment response were 3.0, 1.3, and 1.4 for CAR, PLR, and NLR, respectively. The PFS and OS were significantly longer when the treatment response values for changes in CAR, PLR, and NLR were below these cutoff values (CAR: OS, p < 0.0001 and PFS, p < 0.0001; PLR: OS, p = 0.0289 and PFS, p = 0.0302; and NLR: OS, p = 0.0077 and PFS, p = 0.0044)., Conclusions: Measurement of the changes in CAR, PLR, and NLR could provide a simple, prompt, noninvasive method to evaluate response to nivolumab monotherapy., Trial Registration: This study is registered with number K2023006., (© 2024. The Author(s).)

Competing Interests: Competing interests: LDR reports consulting for Cardiff Oncology, Nutcracker Therapeutics, and AXDEV as well as participation in the Steering Committee for the Global Coalition of Adaptive Research. The remaining authors do not report any relevant conflicts of interest. All authors guarantee the manuscript.

Objective: The objective of this study was to assess the oncologic outcome of surgically-treated patients with early-stage, intermediate-risk cervical cancer according to postoperative therapy modality., Methods: This retrospective cohort study queried the Japanese Gynecologic Oncology Group's nationwide surgical data platform. The study population was 1084 patients with stage IB cervical cancer who underwent primary radical hysterectomy and lymphadenectomy from 2004 to 2008. Histology type-incorporated intermediate-risk factor patterns were clustered into three groups based on recurrence risk. Oncologic outcomes were assessed per postoperative therapy: external beam radiotherapy alone, concurrent chemo-radiotherapy, chemotherapy alone, and no treatment., Results: Histology-incorporated intermediate-risk groups included: no lympho-vascular space invasion in any histology, or squamous cell carcinoma with lympho-vascular space invasion but no deep stromal invasion (n=559, 51.6%, group 1); squamous cell carcinoma with both lympho-vascular space invasion and deep cervical stromal invasion (n=281, 25.9%; group 2); and non-squamous histology with lympho-vascular space invasion (n=244, 22.5%; group 3). The 5-year disease-free survival rates were 93.3%, 89.3%, and 82.5% for group 1,-2, and -3, respectively (p<0.001), with group 3 exhibiting an almost three-fold increased recurrence risk compared with group 1 (adjusted-hazard ratio (aHR) 2.70, 95% confidence interval (CI) 1.70-4.32), followed by group 2 (aHR 1.67, 95% CI 1.01 to 2.75). Disease-free survival was similar across the postoperative therapy groups: 5 year rates for external beam radiotherapy alone, concurrent chemo-radiotherapy, chemotherapy alone, and no postoperative treatment, 94.8%, 87.2%, 93.6%, and 94.2% for group 1 (p=0.294); 85.0%, 93.3%, 87.3%, and 90.5% for group 2 (p=0.578); and 85.4%, 83.1%, 80.5%, and 83.3% for group 3 (p=0.876). The aHR for disease-free survival comparing no postoperative treatment to external beam radiotherapy alone was 1.10 (95% CI 0.37 to 3.28), 0.71 (95% CI 0.29 to 1.79), and 1.21 (95% CI 0.42 to 3.51) for group 1, group 2, and group 3, respectively. The observed exposure-outcome associations were similar for cause-specific survival (all, p>0.05)., Conclusion: In this retrospective investigation in Japan, active surveillance without postoperative therapy following radical hysterectomy and lymphadenectomy was not associated with oncologic outcome in early-stage, intermediate-risk cervical cancer., Competing Interests: Competing interests: Research grant, Bristol Myers Squibb, honorarium, AstraZenaca (MH); none for the other authors., (© IGCS and ESGO 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Developing long bones alter their shape while maintaining uniform cortical thickness via coordinated activity of bone-forming osteoblasts and bone-resorbing osteoclasts at periosteal and endosteal surfaces, a process we designate trans-pairing. Two types of trans-pairing shift cortical bone in opposite orientations: peri-forming trans-pairing (peri-t-p) increases bone marrow space and endo-forming trans-pairing (endo-t-p) decreases it, via paired activity of bone resorption and formation across the cortex. Here, we focused on endo-t-p in growing bones. Analysis of endo-t-p activity in the cortex of mouse fibulae revealed osteoclasts under the periosteum compressed by muscles, and expression of RANKL in periosteal cells of the cambium layer. Furthermore, mature osteoblasts were localized on the endosteum, while preosteoblasts were at the periosteum and within cortical canals. X-ray tomographic microscopy revealed the presence of cortical canals more closely associated with endo- than with peri-t-p. Sciatic nerve transection followed by muscle atrophy and unloading induced circumferential endo-t-p with concomitant spread of cortical canals. Such canals likely supply the endosteum with preosteoblasts from the periosteum under endo-t-p, allowing bone shape to change in response to mechanical stress or nerve injury., Competing Interests: Competing interests The authors declare no competing or financial interests., (© 2024. Published by The Company of Biologists Ltd.)

Background: Immune checkpoint inhibitors (ICIs) are widely adapted for recurrent or metastatic head and neck cancer (RM-HNC), and various studies on its prognostic factors have been reported. We aimed to elucidate the prognostic factors of ICI treatment for RM oral cancer (RM-OC) in a retrospective study., Methods: We retrospectively reviewed patients with RM-OC treated with ICIs (nivolumab and pembrolizumab) at our department from May 2017 to February 2023. The objective response rate (ORR) for ICI treatment and the relationship between several potential prognostic factors, progression-free survival (PFS), and overall survival (OS) were analyzed statistically., Results: The investigation enrolled 31 patients, 16 with nivolumab and 15 with pembrolizumab. There were no significant differences in the ORR or disease control rate between the nivolumab and pembrolizumab groups (p = 0.4578 and 0.2524). In multivariate analysis, the prognostic nutritional index (PNI) and C-reactive protein to albumin ratio (CAR) exhibited statistical correlations with PFS, whereas the use of antibiotics and proton pump inhibitors (PPIs), neutrophil to lymphocyte ratio (NLR), and PNI demonstrated statistical associations with OS., Conclusion: Our findings imply that the use of antibiotics and PPIs, which can modify the gut microbiota, may also serve as a prognostic determinant for ICI treatment in RM-OC, consistent with previous studies. Additionally, PNI may be essential in affecting the survival rates of both PFS and OS and could be an exceedingly valuable inflammatory biomarker for RM-OC., Competing Interests: Declaration of competing interest None declared., (Copyright © 2024 Elsevier Masson SAS. All rights reserved.)

Objective: Hospital treatment volume affects survival in patients with endometrial cancer; notably, initial treatment at high-volume centers improves survival outcomes. Our study assessed the effect of hospital treatment volume on cost-effectiveness and survival outcomes in patients with endometrial cancer in Japan., Methods: A decision-analytic model was evaluated using the following variables and their impact on cost-effectiveness: 1) hospital treatment volume (low-, intermediate-, and high-volume centers) and 2) postoperative recurrent risk factors based on pathological findings (high- and intermediate-risk or low-risk). Data were obtained from the Japan Society of Obstetrics and Gynecology database, systematic literature searches, and the Japanese Diagnosis Procedure Combination database. Quality-adjusted life years (QALY) was used as a measure of effectiveness. The model was built from a public healthcare perspective and the impact of uncertainty was assessed using sensitivity analyses., Results: A base-case analysis showed that the incremental cost-effectiveness ratio at high-volume centers was below a willingness-to-pay (WTP) threshold of ¥5,000,000 with a maximum of ¥3,777,830/4.28 QALY for the high- and intermediate-risk group, and ¥2,316,695/4.57 QALY for the low-risk group. Treatment at the high-volume centers showed better efficiency and cost-effectiveness in both strategies compared to intermediate- or low-volume centers. Sensitivity analyses showed that the model outcome was robust to changes in input values. With the WTP threshold, treatment at high-volume centers remained cost-effective in at least 73.6% and 78.2% of iterations for high- and intermediate-risk, and low-risk groups, respectively., Conclusion: Treatment at high-volume centers is the most cost-effective strategy for guiding treatment centralization in patients with endometrial cancer., Competing Interests: Honorarium, Bristol Myers Squibb (H.M) and none for others., (© 2024. Asian Society of Gynecologic Oncology, Korean Society of Gynecologic Oncology, and Japan Society of Gynecologic Oncology.)

Although previous polygenic risk score (PRS) studies for cardiovascular disease (CVD) focused on incidence, few studies addressed CVD mortality and quantified risks by environmental exposures in different genetic liability groups. This prospective study aimed to examine the associations of blood pressure PRS with all-cause and CVD mortality and to quantify the attributable risk by modifiable lifestyles across different PRS strata. 9,296 participants in the Japan Multi-Institutional Collaborative Cohort Study without hypertension at baseline were analyzed in this analysis. PRS for systolic blood pressure and diastolic blood pressure (PRS SBP and PRS DBP ) were developed using publicly available Biobank Japan GWAS summary statistics. CVD-related mortality was defined by the International Classification of Diseases 10th version (I00-I99). Cox-proportional hazard model was used to examine associations of PRSs and lifestyle variables (smoking, drinking, and dietary sodium intake) with mortality. During a median 12.6-year follow-up period, we observed 273 all-cause and 41 CVD mortality cases. Compared to the middle PRS group (20-80th percentile), adjusted hazard ratios for CVD mortality at the top PRS group ( > 90th percentile) were 3.67 for PRS SBP and 2.92 for PRS DBP . Attributable risks of CVD mortality by modifiable lifestyles were higher in the high PRS group ( > 80th percentile) compared with the low PRS group (0-80th percentile). In summary, blood pressure PRS is associated with CVD mortality in the general Japanese population. Our study implies that integrating PRS with lifestyle could contribute to identify target populations for lifestyle intervention even though improvement of discriminatory ability by PRS alone is limited., (© 2024. The Author(s), under exclusive licence to The Japanese Society of Hypertension.)

Purpose: Intraoral vertico-sagittal ramus osteotomy (IVSRO) was first reported by Choung in 1992 as a surgical procedure to decrease postoperative condylar dislocation. In 2017, Iwanaga et al. developed modified L-shaped IVSRO (mIVSRO) to reduce postoperative nerve dysfunction and achieved favorable outcomes. This study aimed to clarify the effect of mIVSRO on changes in temporomandibular joint (TMJ) symptoms and three-dimensional condylar position., Methods: We conducted a retrospective study of thirty sides in fifteen Japanese adults diagnosed with jaw deformities who underwent mIVSRO and sagittal split ramus osteotomy (SSRO). TMJ symptoms were assessed chronologically, and the condylar long axis and the condylar position were analyzed two- and three-dimensionally using axial cephalograms and cone-beam computed tomography., Results: Postoperative TMJ symptoms improved by 90% (9/10 sides) in the mIVSRO group and by 50% (7/14 sides) in the SSRO group. The mIVSRO group exhibited outward rotation of the condylar long axis, while the SSRO group exhibited inward rotation. Moreover, mIVSRO induced residual anteromedial-inferior deviation of the condyle. The inclination angle of the condylar process was not significantly different between the two procedures pre- and postoperatively., Conclusion: These results clearly demonstrated the effect of mIVSRO on symptomatic TMJ. Residual changes in the position of the condyle following mIVSRO may not affect jaw function., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objectives: This study aims to assess the effectiveness of super-resolution deep-learning-based reconstruction (SR-DLR), which leverages k-space data, on the image quality of lumbar spine magnetic resonance (MR) bone imaging using a 3D multi-echo in-phase sequence., Materials and Methods: In this retrospective study, 29 patients who underwent lumbar spine MRI, including an MR bone imaging sequence between January and April 2023, were analyzed. Images were reconstructed with and without SR-DLR (Matrix sizes: 960 × 960 and 320 × 320, respectively). The signal-to-noise ratio (SNR) of the vertebral body and spinal canal and the contrast and contrast-to-noise ratio (CNR) between the vertebral body and spinal canal were quantitatively evaluated. Furthermore, the slope at half-peak points of the profile curve drawn across the posterior border of the vertebral body was calculated. Two radiologists independently assessed image noise, contrast, artifacts, sharpness, and overall image quality of both image types using a 4-point scale. Interobserver agreement was evaluated using weighted kappa coefficients, and quantitative and qualitative scores were compared via the Wilcoxon signed-rank test., Results: SNRs of the vertebral body and spinal canal were notably improved in images with SR-DLR (p < 0.001). Contrast and CNR were significantly enhanced with SR-DLR compared to those without SR-DLR (p = 0.023 and p = 0.022, respectively). The slope of the profile curve at half-peak points across the posterior border of the vertebral body and spinal canal was markedly higher with SR-DLR (p < 0.001). Qualitative scores (noise: p < 0.001, contrast: p < 0.001, artifact p = 0.042, sharpness: p < 0.001, overall image quality: p < 0.001) were superior in images with SR-DLR compared to those without. Kappa analysis indicated moderate to good agreement (noise: κ = 0.56, contrast: κ = 0.51, artifact: κ = 0.46, sharpness: κ = 0.76, overall image quality: κ = 0.44)., Conclusion: SR-DLR, which is based on k-space data, has the potential to enhance the image quality of lumbar spine MR bone imaging utilizing a 3D gradient echo in-phase sequence., Clinical Relevance Statement: The application of SR-DLR can lead to improvements in lumbar spine MR bone imaging quality., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The blood-brain barrier is a unique function of the microvasculature in the brain parenchyma that maintains homeostasis in the central nervous system. Blood-brain barrier breakdown is a common pathology in various neurological diseases, such as Alzheimer's disease, stroke, multiple sclerosis, and Parkinson's disease. Traditionally, it has been considered a consequence of neuroinflammation or neurodegeneration, but recent advanced imaging techniques and detailed studies in animal models show that blood-brain barrier breakdown occurs early in the disease process and may precede neuronal loss. Thus, the blood-brain barrier is attractive as a potential therapeutic target for neurological diseases that lack effective therapeutics. To elucidate the molecular mechanism underlying blood-brain barrier breakdown and translate them into therapeutic strategies for neurological diseases, there is a growing demand for experimental models of human origin that allow for functional assessments. Recently, several human induced pluripotent stem cell-derived blood-brain barrier models have been established and various in vitro blood-brain barrier models using microdevices have been proposed. Especially in the Alzheimer's disease field, the human evidence for blood-brain barrier dysfunction has been demonstrated and human induced pluripotent stem cell-derived blood-brain barrier models have suggested the putative molecular mechanisms of pathological blood-brain barrier. In this review, we summarize recent evidence of blood-brain barrier dysfunction in Alzheimer's disease from pathological analyses, imaging studies, animal models, and stem cell sources. Additionally, we discuss the potential future directions for blood-brain barrier research., (Copyright © 2024 Copyright: © 2024 Neural Regeneration Research.)

Prognosis for patients undergoing hematopoietic cell transplantation (HCT) has been improving. Short-term survival information, such as crude survival rates that consider deaths immediately after the transplantation, may not be sufficiently useful for assessing long-term survival. Using the data of the Japanese HCT registry, the net survival rate of patients who survived for a given period was determined according to age, disease, and type of transplant. We included a total of 41,716 patients who received their first allogeneic hematopoietic cell transplantation between 1991 and 2015. For each disease, age group, graft source subcategory, net survival was calculated using the Pohar-Perme method, and 5-year conditional net survival (CS) was calculated. Ten-year net survivals of total patient cohort were 41.5% and 47.4% for males and females, respectively. Except for myelodysplastic syndrome, multiple myeloma, and adult T-cell leukemia/lymphoma, 5-year CS for 5-year transplant survivors exceeded 90%. CS was especially high for aplastic anemia, of which was over 100% for children and younger adults receiving cord blood, suggesting that these patients have similar longevity to an equivalent group from the general population. These findings provide useful information for long-term survival, and can serve as benchmark for comparisons among registries, including other cancers., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

There has been growing evidence suggesting that diabetes may be associated with increased liver cancer risk. However, studies conducted in Asian countries are limited. This project considered data of 968,738 adults pooled from 20 cohort studies of Asia Cohort Consortium to examine the association between baseline diabetes and liver cancer incidence and mortality. Cox proportional hazard model and competing risk approach was used for pooled data. Two-stage meta-analysis across studies was also done. There were 839,194 subjects with valid data regarding liver cancer incidence (5654 liver cancer cases [48.29/100,000 person-years]), follow-up time and baseline diabetes (44,781 with diabetes [5.3%]). There were 747,198 subjects with valid data regarding liver cancer mortality (5020 liver cancer deaths [44.03/100,000 person-years]), follow-up time and baseline diabetes (43,243 with diabetes [5.8%]). Hazard ratio (HR) (95% confidence interval [95%CI]) of liver cancer diagnosis in those with vs. without baseline diabetes was 1.97 (1.79, 2.16) (p < .0001) after adjusting for baseline age, gender, body mass index, tobacco smoking, alcohol use, and heterogeneity across studies (n = 586,072; events = 4620). Baseline diabetes was associated with increased cumulative incidence of death due to liver cancer (adjusted HR (95%CI) = 1.97 (1.79, 2.18); p < .0001) (n = 595,193; events = 4110). A two-stage meta-analytic approach showed similar results. This paper adds important population-based evidence to current literature regarding the increased incidence and mortality of liver cancer in adults with diabetes. The analysis of data pooled from 20 studies of different Asian countries and the meta-analysis across studies with large number of subjects makes the results robust., (© 2024 UICC.)

Background: Genetic polymorphisms of molecules are known to cause individual differences in the therapeutic efficacy of anticancer drugs. However, to date, germline mutations (but not somatic mutations) for anticancer drugs have not been adequately studied. The objective of this study was to investigate the association between germline polymorphisms of gemcitabine metabolic and transporter genes with carbohydrate antigen 19-9 (CA 19-9) response (decrease ≥50% from the pretreatment level at 8 weeks) and overall survival (OS) in patients with metastatic pancreatic cancer who receive gemcitabine-based chemotherapy., Methods: This multicenter, prospective, observational study enrolled patients with metastatic pancreatic cancer patients who were receiving gemcitabine monotherapy or gemcitabine plus nanoparticle albumin-bound paclitaxel combination chemotherapy. Thirteen polymorphisms that may be involved in gemcitabine responsiveness were genotyped, and univariate and multivariate logistic regression analyses were used to determine the association of these genotypes with CA 19-9 response and OS. The significance level was set at 5%., Results: In total, 180 patients from 11 hospitals in Japan were registered, and 159 patients whose CA 19-9 response could be assessed were included in the final analysis. Patients who had a CA 19-9 response had significantly longer OS (372 vs. 241 days; p = .007). RRM1 2464A>G and RRM2 175T>G polymorphisms suggested a weak association with CA 19-9 response and OS, but it was not statistically significant. COX-2 -765G>C polymorphism did not significantly correlate with CA 19-9 response but was significantly associated with OS (hazard ratio, 2.031; p = .019)., Conclusions: Genetic polymorphisms from the pharmacokinetics of gemcitabine did not indicate a significant association with efficacy, but COX-2 polymorphisms involved in tumor cell proliferation might affect OS., (© 2024 American Cancer Society.)

Epithelial ovarian cancer (EOC) is widely recognized as the most lethal gynecological malignancy; however, its early-stage detection remains a considerable clinical challenge. To address this, we have introduced a new method, named Comprehensive Serum Glycopeptide Spectral Analysis (CSGSA), which detects early-stage cancer by combining glycan alterations in serum glycoproteins with tumor markers. We detected 1712 glycopeptides using liquid chromatography-mass spectrometry from the sera obtained from 564 patients with EOC and 1149 controls across 13 institutions. Furthermore, we used a convolutional neural network to analyze the expression patterns of the glycopeptides and tumor markers. Using this approach, we successfully differentiated early-stage EOC (Stage I) from non-EOC, with an area under the curve (AUC) of 0.924 in receiver operating characteristic (ROC) analysis. This method markedly outperforms conventional tumor markers, including cancer antigen 125 (CA125, 0.842) and human epididymis protein 4 (HE4, 0.717). Notably, our method exhibited remarkable efficacy in differentiating early-stage ovarian clear cell carcinoma from endometrioma, achieving a ROC-AUC of 0.808, outperforming CA125 (0.538) and HE4 (0.557). Our study presents a promising breakthrough in the early detection of EOC through the innovative CSGSA method. The integration of glycan alterations with cancer-related tumor markers has demonstrated exceptional diagnostic potential., (© 2024. The Author(s).)

The Japanese Society of Mood Disorders (JSMD) published treatment guidelines of bipolar disorder in 2011. The present guidelines incorporating new findings were developed to comply to the guidelines of the National Academy of Medicine (NAM) by utilizing systematic reviews and meta-analysis and taking patient and family opinions as well as insights from multiple professional fields into account. They support combination therapy using mood stabilizers and second-generation antipsychotics in many aspects. They also have limitations, including the grouping of mood stabilizers and second-generation antipsychotics when meta-analysis was performed despite their distinct properties, due to the scarcity of drug-specific evidence. Despite the limitations, these guidelines provide clinical decision support for psychiatrists in Japan., (© 2024 The Author(s). Psychiatry and Clinical Neurosciences published by John Wiley & Sons Australia, Ltd on behalf of Japanese Society of Psychiatry and Neurology.)

Reversibly photoswitchable chemical tools have aided in the development of novel approaches in the biomedical field. The visible region of light should be ideal for the biological application of this approach because of its low phototoxicity and deep penetration depth compared to ultraviolet light. Herein, we report a photoswitchable centromere-associated protein E (CENP-E) inhibitor, which is controllable with low-energy blue-green light (around 500 nm) illumination. This photoswitchable tool enabled us to control CENP-E-driven chromosome movements and positioning at subcellular resolutions with low phototoxic effects. This study can contribute to the development of a unique technique for chromosome engineering., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Background: The da Vinci™ Surgical System, recognized as the leading surgical robotic platform globally, now faces competition from a growing number of new robotic surgical systems. With the expiration of key patents, innovative entrants have emerged, each offering unique features to address limitations and challenges in minimally invasive surgery. The hinotori™ Surgical Robot System (hinotori), developed in Japan and approved for clinical use in November 2022, represents one such entrant. This study demonstrates initial insights into the application of the hinotori in robot-assisted surgeries for patients with rectal neoplasms., Methods: The present study, conducted at a single institution, retrospectively reviewed 28 patients with rectal neoplasms treated with the hinotori from November 2022 to March 2024. The surgical technique involved placing five ports, including one for an assistant, and performing either total or tumor-specific mesorectal excision using the double bipolar method (DBM). The DBM uses two bipolar instruments depending on the situation, typically Maryland bipolar forceps on the right and Fenestrated bipolar forceps on the left, to allow precise dissection, hemostasis, and lymph node dissection., Results: The study group comprised 28 patients, half of whom were male. The median age was 62 years and the body mass index stood at 22.1 kg/m 2 . Distribution of clinical stages included eight at stage I, five at stage II, twelve at stage III, and three at stage IV. The majority, 26 patients (92.9%), underwent anterior resection using a double stapling technique. There were no intraoperative complications or conversions to other surgical approaches. The median operative time and cockpit time were 257 and 148 min, respectively. Blood loss was 15 mL. Postoperative complications were infrequent, with only one patient experiencing transient ileus. A median of 18 lymph nodes was retrieved, and no positive surgical margins were identified., Conclusions: The introduction of the hinotori for rectal neoplasms appears to be safe and feasible, particularly when performed by experienced robotic surgeons. The double bipolar method enabled precise dissection and hemostasis, contributing to minimal blood loss and effective lymph node dissection., (© 2024. The Author(s).)

Objective: Although obesity is an important risk factor for endometrial intraepithelial neoplasia (EIN) and uterine cancer, little is known about the trends in use of weight-loss therapy for patients with obesity with EIN and uterine cancer. We examined the use of weight-loss therapy among patients with obesity with EIN and uterine cancer., Methods: The Merative MarketScan Database was used to identify patients aged 18-70 years who were obese and diagnosed with EIN or uterine cancer. The primary treatment for EIN or uterine cancer was categorized as either primary hysterectomy or hormonal therapy. Nutrition counseling, bariatric surgeries, and weight-management medications were identified as weight-loss therapy. We analyzed trends in the use of any weight-loss therapies with Cochran-Armitage tests. A multivariable logistic regression model was developed to examine factors associated with weight-loss therapy use., Results: Overall, 15,374 patients were identified, including 5561 (36.2%) patients with EIN and obesity, and 9813 (63.8%) patients with uterine cancer and obesity. Weight-loss therapy was utilized within 1 year after diagnosis in 480 (8.6%) patients with EIN and in 802 (8.2%) patients with uterine cancer. Use of any weight-loss therapy after diagnosis of EIN increased from 4.1% in 2009 to 12.6% in 2020 (P < .001), and the use of any weight-loss therapy after diagnosis of uterine cancer increased from 4.9% in 2009 to 11.4% in 2020 (P < .001). In a multivariable regression model, younger age and patients with high comorbidity score were associated with a higher likelihood of using any weight-loss therapy., Conclusions: Use of weight-loss therapy has increased, however there is still a significant underuse of this adjunctive therapy in patients with obesity with EIN or uterine cancer., Competing Interests: Declaration of competing interest Dr. Wright has received royalties from UpToDate and the American College of Obstetricians and Gynecologistsand received research funding from Merck. All other authors declare no conflicts of interest. Dr. Suzuki reports receiving payment from The Japan Society for Menopause and Women's Health (JMWH Bayer Grant 2021), from Kanzawa Medical Research Foundation (Oversea Research Grant 2022), and from Mitsui & CO. (U.S.A), INC (Mitsui USA-JMSA Scholarship 2023). Dr. Elkin has received research support from Pfizer., (Copyright © 2024 Elsevier Inc. All rights reserved.)

The construction and utilization of dependable vascular access are essential for hemodialysis. Despite its importance, complications with vascular access are common, significantly impacting patient morbidity and mortality. This report presents a novel approach to treating chronic total occlusion (CTO) in hemodialysis vascular access using the "wire kissing technique" an "externalization and pull-through technique." An 82-year-old woman on hemodialysis had a thrombotic obstruction in her cephalic vein, which conventional methods failed to address. The wire kissing technique allowed the meeting of antegrade and retrograde wires within the CTO lesion, stabilizing the wire and facilitating balloon passage. The externalization and pull-through technique further enabled the balloon to cross the rigid CTO lesion, successfully completing percutaneous transluminal angioplasty (PTA). Post-procedure ultrasonography showed significant improvements in flow volume and resistance index. These techniques, commonly used in coronary and femoral arteries, have not been previously reported for dialysis vascular access. This case highlights a novel and effective solution for overcoming technical difficulties in crossing CTO lesions, potentially improving outcomes in vascular access for hemodialysis patients., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.