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Ventricular assist device (VAD) infections are frequent causes of hospital readmission. The risk factors and optimal preventive strategies for such, including chronic suppressive antibiotics (CSA), remain uncertain. We performed a single-center, retrospective, observational cohort study assessing continuous flow VAD recipients who underwent implantation between 2008 and 2018 in Japan. From primary VAD infection (VADI), we followed the patients for recurrent infection, defined as relapsing VAD-specific (e.g., localized infections) or VAD-related (e.g., bacteremia) infections requiring hospital readmission. CSA was defined as the use of oral antimicrobial agents continued beyond initial antibiotic use until transplantation, VAD withdrawal, VADI recurrence, or death. Survival analysis was performed to identify risk factors for recurrent infection accounting for competing risks (e.g., deaths and transplants). Among 163 eligible patients, 76 patients had VADIs. The main causative organism in primary VADI was Staphylococcus aureus (63%, 48/76). Among them, 41 had recurrent infections, whereas 35 had none during the follow-up period (median, 335 days). Thirty-six patients received CSA for a median of 478 days. Although CSA was associated with a decreased risk of recurrent infection [adjusted sub-distribution hazard ratio (SHR), 0.40; 95% confidence interval (CI), 0.18-0.89; P = 0.03], this protective effect was observed only after primary VAD-specific infection (SHR, 0.28; 95% CI, 0.12-0.64; P < 0.01) but not after VAD-related infection. Surgical procedures during primary VADI were associated with an increased risk (SHR, 2.00; 95% CI, 1.10-3.66; P = 0.02). One patient had an adverse drug reaction. CSA may be an effective approach to limit relapsing VADIs following a primary VAD-specific infection with minimal adverse events., Importance: Ventricular assist device infections (VADIs) are a significant complication leading to hospital readmissions. However, the risk factors and optimal preventive strategies for VADI remain unclear. This study investigated the effectiveness of chronic suppressive antibiotic therapy in patients with VADI. We found that the use of chronic suppressive antibiotic therapy was associated with a reduction in the risk of VADI recurrence with few adverse reactions. Our findings suggest the potential benefit of chronic suppressive antibiotics in preventing infections in selected cases. Our findings are relevant for the management of patients with ventricular assist devices awaiting heart transplantation, providing valuable insights for clinical practice., Competing Interests: H.K. reports receiving consultation fees from Mitsubishi-Tanabe Pharma Corporation, and EPS Corporation, and a speaker fee from Chugai Pharmaceutical Co., Ltd. He is affiliated with the Department of Health Quality Assessment at the University of Tokyo, a social collaboration department supported by the National Clinical Database, Johnson & Johnson K.K., Nipro Corporation, and Intuitive Surgical Sàrl. S.H. has received grants or contracts from Shinogi & Company Ltd., and received payments or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational activities from Shinogi & Co., Ltd., MSD, Daiichi Sankyo, and Nissui Pharmaceutical. No other competing financial interests declared.

Background: Ischemic priapism is a rare pathological condition, and delayed intervention can result in irreversible sequelae. Most cases are attributed to the use of antipsychotics. The blockade of α1-adrenergic receptors is thought to be associated with the disease onset, although data supporting this hypothesis are lacking. No consensus regarding the optimal choice of medication is available., Case Presentation: A 59-year-old man with schizophrenia, who had been receiving long-acting injections of risperidone, developed ischemic priapism after receiving paliperidone treatment. Following improvement in ischemic priapism, we administered a combination of aripiprazole and olanzapine, which improved his psychiatric symptoms. We did not observe any recurrence of ischemic priapism., Conclusions: Switching the antipsychotic drug causing ischemic priapism to patients having a relatively low affinity for α1-adrenergic receptors may enable the treatment of schizophrenia without recurrence of ischemic priapism. In addition to the affinity for α1-adrenergic receptor, differences in metabolic enzyme types and antipsychotic doses may be involved in the occurrence of ischemic priapism. Accumulating evidence is necessary to establish guidelines for selecting medication of patients with ischemic priapism., (© 2024 The Author(s). Neuropsychopharmacology Reports published by John Wiley & Sons Australia, Ltd on behalf of The Japanese Society of Neuropsychopharmacology.)

Silica polymorphs occur under various pressures and temperature conditions, and their characteristics can be used to better understand the complex metamorphic history of planetary materials. Here, we conducted isothermal heating experiments of silica polymorphs in basaltic eucrites to assess their formation and stability. We revealed that each silica polymorph exhibits different metamorphic responses: (1) Quartz recrystallizes into cristobalite when heated at ≥ 1040 °C. (2) Monoclinic (MC) tridymite recrystallizes into no other polymorphs when heated at ≤ 1070 °C. (3) Silica glass recrystallizes into quartz when heated at 900-1010 °C, and recrystallize into cristobalite when heated at ≥ 1040 °C. These results suggest that MC tridymite in eucrites does not recrystallize into other polymorphs during the reheating events, nor does it recrystallize from other silica phases below the solidus temperature of eucrite (~ 1060 °C). Additionally, we found that pseudo-orthorhombic (PO) tridymite crystallizes from quenched melts in the samples heated at ≥ 1070 °C. Previously, cristobalite has been considered as the initial silica phase, which crystallizes from eucritic magma. Our findings suggest that the first crystallizing silica minerals may not always be cristobalite. These require a reconsideration of the formation process of silica minerals in eucrites., (© 2024. The Author(s).)

Background/aim: Cancer-associated systemic inflammatory response is a pivotal indicator of tumor progression and prognosis in various cancers. "Lymphocyte × albumin (LA)" is a prognostic inflammatory marker in rectal cancer. This study examined the correlation between LA, complete adjuvant chemotherapy (ACT), and prognosis in patients with gastric cancer (GC) who underwent radical gastrectomy., Patients and Methods: We retrospectively evaluated 108 patients with stage II/III GC who underwent radical gastrectomy at our institute between January 2015 and December 2021. Survival was assessed using Kaplan-Meier and Cox regression analyses. Factors associated with complete ACT were identified using logistic regression analysis., Results: Of the 108 patients with GC, 60 (55.6%) and 41 (38.0%) initiated and completed ACT, respectively. In multivariate analysis, the pre-operative LA was an independent factor for complete ACT [hazard ratio (HR)=0.35, 95% confidence interval (CI)=0.121-0.995; p=0.049]. In addition, age, pre-operative creatinine clearance, neutrophil-to-lymphocyte ratio, modified Glasgow prognostic score, and poor overall survival were significantly associated with low LA (<7,474). LA was an independent prognostic factor for overall survival in univariate analysis (HR=2.29, 95%CI=1.020-5.145; p=0.045) but not in multivariate analysis (HR=2.00, 95%CI=0.882-4.552; p=0.097)., Conclusion: Pre-operative LA is a useful marker for predicting complete ACT and prognosis of patients with GC following radical gastrectomy., (Copyright © 2024 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Aim: Patient education is crucial for preventing chronic kidney disease (CKD) progression, but adequate educational time is not always available in standard nephrology outpatient clinics. However, usefulness of educational materials provided by healthcare providers in educational settings has been reported. This study aimed to compare the efficacy of pamphlet and video materials in increasing CKD knowledge at a nephrology clinic using waiting time., Materials and Methods: 44 CKD stage 3 - 5 patients were randomly assigned to either pamphlet or video education group, receiving a single session during an outpatient visit. We evaluated the objective CKD knowledge score, perceived kidney disease knowledge score, self-care scores, and amount of estimated salt intake before and after the educational intervention., Results: In both groups, the educational intervention significantly increased objective and perceived CKD knowledge scores (p < 0.001). No significant differences in increase in total knowledge scores between both groups were observed; however, different educational effects were observed in several individual knowledge items such as urinary protein and CKD stages. In both groups, self-care scores and amount of estimated salt intake did not change significantly before and after the intervention, but amount of estimated salt intake significantly decreased in patients with a history of dietary guidance (p = 0.044)., Conclusion: A single educational session with simple materials during outpatient waiting time at the nephrology clinic visit significantly improved patients' CKD knowledge, and suitable educational methods may differ according to knowledge items. Furthermore, patients who receive dietary guidance with specific instructions might exhibit salt reduction behavior through the use of educational materials.

Objectives: Some studies reported a relationship between life-space mobility (LSM) and frailty assessed by physical aspects; however, a more comprehensive discussion of frailty is underdeveloped. In addition, previous studies have focused only on older Euro-American people. Therefore, we aimed to examine LSM-frailty relationships in community-dwelling older Japanese persons using physical and comprehensive frailty indices., Design: A cross-sectional study., Setting and Participants: We used the data of 8898 older adults from a baseline survey of the Kyoto-Kameoka Study in Japan., Methods: The validated life-space assessment (LSA) was used to evaluate LSM and categorized it into quartiles. Two validated indices were used to evaluate frailty: the Kihon Checklist (KCL) and the simple Frailty Screening Index (FSI). Multivariable logistic regression was used to determine the relationships between LSM scores and frailty., Results: The mean age (SD) of the participants was 73.4 (6.3) years, and 53.3% were women. The mean LSM score of the study participants was 53.0. The prevalence of frailty by KCL and FSI was 40.7% and 16.8%, respectively. Significant differences between LSM score and frailty prevalence were observed [KCL: Q1, reference; Q2, odds ratio (OR) 0.53, 95% CI 0.45-0.62; Q3, OR 0.30, 95% CI 0.25-0.35; Q4: OR 0.22, 95% CI 0.18-0.26, P for trend <.001; FSI: Q1, reference; Q2, OR 0.57, 95% CI 0.48-0.68; Q3: OR 0.38, 95% CI 0.31-0.46; Q4: OR 0.35, 95% CI 0.28-0.42, P for trend <.001]. Similar results were observed when LSM scores were examined at 10-point intervals, with LSM and frailty exhibiting an L-shaped relationship. The LSM score dose-response curve at which the OR for frailty plateaued among older individuals was approximately 81-90 score., Conclusions and Implications: LSM score and frailty prevalence exhibited L-shaped relationships in community-dwelling older persons. This study's findings provide useful data for setting LSM targets for preventing frailty in community-dwelling older persons., Competing Interests: Disclosure The authors declare no conflicts of interest., (Copyright © 2024 Post-Acute and Long-Term Care Medical Association. Published by Elsevier Inc. All rights reserved.)

The aim of this study was to identify anatomical and clinical factors associated with limb-based patency (LBP) loss, major adverse limb events (MALEs), and poor amputation-free survival (AFS) after an infrapopliteal arterial bypass (IAB) surgery according to the Global Limb Anatomic Staging System. A retrospective analysis of patients undergoing IAB surgery between January 2010 and December 2021 at a single institution was performed. Two-year AFS, freedom from LBP loss, and freedom from MALEs were assessed using the Kaplan-Meier method. Anatomical and clinical predictors were assessed using multivariate analysis. The total number of risk factors was used to calculate risk scores for subsequent categorization into low-, moderate-, and high-risk groups. IABs were performed on 103 patients. The rates of two-year freedom from LBP loss, freedom from MALEs, and AFS were 71.3%, 76.1%, and 77.0%, respectively. The multivariate analysis showed that poor run-off beyond the ankle and a bypass vein caliber of < 3 mm were significantly associated with LBP loss and MALEs. Moreover, end-stage renal disease, non-ambulatory status, and a body mass index of < 18.5 were significantly associated with poor AFS. The rates of freedom from LBP loss and MALEs and the AFS rate were significantly lower in the high-risk group than in the other two groups (12-month low-risk rates: 92.2%, 94.8%, and 94.4%, respectively; 12-month moderate-risk rates: 58.6%, 84.6%, and 78.3%, respectively; 12-month high-risk rates: 11.1%, 17.6%, and 56.2%, respectively; p < 0.001, p < 0.001, and p < 0.001, respectively). IAB is associated with poor clinical outcomes in terms of LBP, MALEs, and AFS in high-risk patients. Risk stratification based on these predictors is useful for long-term prognosis., (© 2024. The Author(s).)

Invasive aspergillosis (IA) is a rare but fatal disease among liver transplant recipients (LiTRs). We performed a multicenter 1:2 case-control study comparing LiTRs diagnosed with proven/probable IA and controls with no invasive fungal infection. We included 62 IA cases and 124 matched controls. Disseminated infection occurred only in 8 cases (13%). Twelve-week all-cause mortality of IA was 37%. In multivariate analyses, systemic antibiotic usage (adjusted odds ratio [aOR], 4.74; P = .03) and history of pneumonia (aOR, 48.7; P = .01) were identified as independent risk factors associated with the occurrence of IA. Moreover, reoperation (aOR, 5.99; P = .01), systemic antibiotic usage (aOR, 5.03; P = .04), and antimold prophylaxis (aOR, 11.9; P = .02) were identified as independent risk factors associated with the occurrence of early IA. Among IA cases, Aspergillus colonization (adjusted hazard ratio [aHR], 86.9; P < .001), intensive care unit stay (aHR, 3.67; P = .02), disseminated IA (aHR, 8.98; P < .001), and dialysis (aHR, 2.93; P = .001) were identified as independent risk factors associated with 12-week all-cause mortality, while recent receipt of tacrolimus (aHR, 0.11; P = .001) was protective. Mortality among LiTRs with IA remains high in the current era. The identified risk factors and protective factors may be useful for establishing robust targeted antimold prophylactic and appropriate treatment strategies against IA., Competing Interests: Declaration of competing interest The authors of this manuscript have conflicts of interest to disclose as described by the American Journal of Transplantation. J. Hand reports research grant funding from Pfizer, Janssen, Scynexis, and GlaxoSmithKline. D. Neofytos has received research support from MSD and Pfizer and consulting fees from MSD, Pfizer, Basilea, and Gilead. N.J. Mueller is on the scientific advisory board of Takeda MSD, and Pfizer and has received travel support from Biotest. M. Luong is on the Scientific Advisory Board of Takeda and Merck. S. Husain reports grant funding from Merck, Astellas, ScynexisInc, Pulmocide, Ltd, and Gilead Sciences Inc, outside the submitted work. All other authors have no potential conflicts., (Copyright © 2024. Published by Elsevier Inc.)

Background: Co-infection with Klebsiella pneumoniae presents a significant concern in hospitalized patients with coronavirus disease (COVID-19), increasing the risk of severe disease progression. Hypervirulent (hv) and hypermucoviscous (hm) K. pneumoniae (Kp) has gained prominence in Asia due to its capacity to cause invasive community-acquired infections. However, recognition of hvKp/hmKp co-infections in the context of COVID-19 remains limited. We report a severe case of rapidly progressing co-infection with hmKp exhibiting "difficult-to-diagnose" phenotypes in a hospitalized patient with COVID-19., Case Presentation: A 61-year-old woman with COVID-19 initially exhibited mild symptoms resembling the common cold. However, her condition rapidly deteriorated over 7 days, leading to hospital admission with the development of dyspnea. The patient required supplemental oxygen, antibiotic treatment, and mechanical ventilation. Gram-negative bacteria with atypical phenotypes were isolated from alveolar lavage fluid and blood cultures. Both strains formed small, glossy, non-lactose-fermenting colonies on clinically relevant media and were susceptible to ampicillin. Conventional biochemical tests failed to identify the Enterobacteriales strains owing to the urease-negative phenotype. Consequently, the identification of K. pneumoniae was difficult until matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS) analysis was performed. A positive string test indicated mucoviscosity, but with variability in the material used for stretching colonies. Whole-genome sequencing performed on the MiSeq and GridION platforms revealed the blood-derived strain JARB-RN-0063 as belonging to serotype K1 and sequence type (ST) 82. The hvKp-associated genes rmpA and iroCD were located on a 5.0-Mb chromosome, and iucABCD-iutA was identified on a 217.9-kb IncFIB(K)/IncR-type plasmid. Therefore, JARB-RN-0063 was genetically classified as hvKp with a Kleborate virulence score of 3. The intrinsic penicillinase gene bla SHV was defective owing to an IS1F element insertion, resulting in the strain being atypically susceptible to ampicillin., Conclusions: This is the first case of severe COVID-19-associated co-infection with a difficult-to-diagnose K. penummoniae strain. Notably, co-infection by the hmKp K1-ST82 clone exhibited atypical phenotypes, including stunted growth, non-lactose fermentation, urease-negative reaction, ampicillin susceptibility, and abnormal mucoviscosity, posing diagnostic challenges for clinical laboratories and impedes the identification of hvKp/hmKp. Delayed identification may worsen patient outcomes, highlighting the need for increased clinical awareness of such difficult-to-diagnose clones to prevent deterioration., (© 2024. The Author(s).)

Background: Segmental absence of intestinal musculature (SAIM) is a partial defect of intestinal muscularis propria without diverticulum. Many reports indicate that the increase in intestinal pressure caused by enemas or endoscopic examinations leads to bowel perforation, but there are few reports involving malignant tumors. Moreover, few reports have had good outcomes after performing one-stage intestinal anastomosis., Case Presentation: A 60-year-old male came to the office with right-side abdominal pain, and was diagnosed with acute generalized peritonitis caused by ascending colon perforation. Emergency laparotomy was performed, and oval and smooth perforation at the ascending colon was observed, which caused ascites with feces. In addition, there was a tumor on the distal side. The terminal ileum was not dilated, so the cause of the perforation was more likely the SAIM-related thin intestinal wall rather than increased internal intestinal pressure due to obstruction of the tumor. Therefore, a right hemicolectomy with functional end-to-end anastomosis (FEEA) between the ascending colon and ileum was performed, rather than creating a stoma. On pathological examination, the resected bowel segments had a partial defect of intestinal muscularis propria around the perforation, leading to the diagnosis of SAIM. The patient had a favorable postoperative course without anastomotic issues and was discharged safely., Conclusions: This case implies that initial intestinal anastomosis can be performed without creating a stoma when SAIM is suspected from the shape of the perforation and proximal intestine. This case report suggests surgeons should keep SAIM in mind during operations for colon perforations., (© 2024. The Author(s).)

Background: Dexamethasone is currently administered for Coronavirus disease 2019(COVID-19); however, there are concerns about its effect on specific antibodies' production. The aim of this study was to evaluate whether specific antibodies were affected by COVID-19 severity and corticosteroid treatment., Methods: Of 251 confirmed COVID-19 patients admitted to our hospital between January 26 and August 10, 2020, the early period of the pandemic, 75 patients with sera within 1 month of onset and 1 month or longer were included in the research. A total of 253 serum samples from these patients were collected. The levels of specific antibodies for severe acute respiratory syndrome coronavirus 2(SARS-CoV-2), immunoglobulin G (IgG) and M (IgM), were measured retrospectively. The results were compared separately of each COVID-19 severity, and with or without corticosteroid treatment., Results: Among the 75 patients, 47, 18, and 10 had mild, moderate, and severe disease, respectively. The median age was 53.0 years and 22 (29%) were women. The most common comorbidities were hypertension and dyslipidemia. Corticosteroids were administered to 20 (27%) and 10 (53%), patients with moderate and severe disease, respectively. The positivity rates IgM increased first, and IgG was almost always positive after day 16, regardless of the severity of COVID-19. On days 6-10, both IgG and IgM positivity rates were higher in patients with moderate disease than in those with mild or severe disease. In patients with moderate disease, IgG positivity was similar over time, regardless of corticosteroid treatment., Conclusions: In COVID-19 patients, specific IgG is positive and maintained for a long period of time, even after corticosteroid treatment. The effect of corticosteroid treatment in a COVID-19 epidemiological study using specific IgG antibodies was considered minor. COVID-19 patients were more likely to receive oxygen if IgM was positive 1 week after onset, but not mechanical ventilation. IgM measurement 1 week after onset may predict COVID-19 severity., (© 2024. The Author(s).)

Autism Spectrum Disorder (ASD) is a developmental disorder characterized by impaired social communication and repetitive behaviors. In recent years, a pharmacological mouse model of ASD involving maternal administration of valproic acid (VPA) has become widely used. Newborn pups in this model show an abnormal balance between excitatory and inhibitory (E/I) signaling in neurons and exhibit ASD-like behavior. However, the molecular basis of this model and its implications for the pathogenesis of ASD in humans remain unknown. Using quantitative secretome analysis, we found that the level of leucine-rich repeat and immunoglobulin domain-containing protein 2 (Lingo2) was upregulated in the conditioned medium of VPA model neurons. This upregulation was associated with excitatory synaptic organizer activity. The secreted form of the extracellular domain of Lingo2 (sLingo2) is produced by the transmembrane metalloprotease ADAM10 through proteolytic processing. sLingo2 was found to induce the formation of excitatory synapses in both mouse and human neurons, and treatment with sLingo2 resulted in an increased frequency of miniature excitatory postsynaptic currents in human neurons. These findings suggest that sLingo2 is an excitatory synapse organizer involved in ASD, and further understanding of the mechanisms by which sLingo2 induces excitatory synaptogenesis is expected to advance our understanding of the pathogenesis of ASD., (© 2024. The Author(s).)

Conotruncal heart defects are severe congenital malformations of the outflow tract, including truncus arteriosus (TA) and double-outlet right ventricle (DORV). TA is a severe congenital heart disease (CHD) in which the main arterial outflow tract of the heart fails to separate. We recently reported TMEM260 (NM&#95;017799.4), c.1617del (p.Trp539Cysfs*9), as a major cause of TA in the Japanese population (TMEM260 Keio-Tohoku variant) comparable to the prevalence of the 22q11.2 deletion syndrome, which accounts for 12%-35% of TA. However, no other major causes of TA have not been identified. Here, we report a family that included a TA patient and a DORV patient, harboring the compound heterozygous variants of TMEM260, a 7066-bp deletion encompassing exons 6-7 and c.1393C > T, p.(Gln465*). The allele frequency of the 7066-bp deletion was particularly high in the Japanese population (0.17%). Based on the allele frequency of this deletion and c.1617del (0.36%) in the Japanese population, TMEM260 variants might be associated with more than half of the Japanese patients with TA. This study showed that TMEM260 pathogenic variants might be the most common cause of TA in the Japanese population and could explain the wide spectrum of phenotypes associated with TMEM260-related CHD, including DORV, demonstrating the usefulness of genetic testing in Japanese patients with TA., (© 2024 The Author(s). American Journal of Medical Genetics Part A published by Wiley Periodicals LLC.)

Doubly labeled water is gold standard for measuring total energy expenditure (TEE). Measurements using the method are sensitive to the isotope dilution space ratio (DSR). Accuracy and precision of the method might be improved if we could identify factors influencing DSR. We evaluated the potential associations of age, sex, ethnicity, anthropometry, body composition, turnover rates of the isotopes, and geographical elevation with DSR. We used univariate regression analysis to explore the relationships between the continuous variables and analysis of variance to test the relationships between the categorical variables with DSR. Subsequently, we used general linear model (GLM) and 1-way analysis of variance to evaluate the simultaneous associations of age, sex, ethnicity, fat-free mass (FFM) and fat mass (FM) on DSR. From 5678 measurements complied from studies around the world with diverse ethnicity and living at various elevations, the mean DSR was 1.0364 ± 0.0141. No meaningful physiologic effect of any of the continuous and categorical variable on DSR was detected. General linear model analysis revealed no effect of FFM and FM (P > 0.33) on DSR, but DSR decreased with age (P < 0.001) among those aged 60 y and older regardless of sex. Among the Whites who were younger than 60 y, DSR was not related to FFM and FM (P = 0.73) but was affected by both age and sex (P < 0.001). Previous estimates of age-related decline in TEE may have overestimated TEE at age 90 y. Validation studies on older participants are required to confirm this finding., Competing Interests: Conflict of interest WWW reports administrative support was provided by Baylor College of Medicine. JRS reports administrative support and article publishing charges were provided by University of Aberdeen. MLN is a Deputy Editor of the Journal of Nutrition but played no role in the Journal’s evaluation of the manuscript. The other authors report no conflicts of interest., (Copyright © 2024 American Society for Nutrition. Published by Elsevier Inc. All rights reserved.)

The fetal liver is a hematopoietic organ, hosting a diverse and evolving progenitor population. While human liver organoids derived from pluripotent stem cells (PSCs) mimic aspects of embryonic and fetal development, they typically lack the complex hematopoietic niche and the interaction between hepatic and hematopoietic development. We describe the generation of human Fetal Liver-like Organoids (FLOs), that model human hepato-hematopoietic interactions previously characterized in mouse models. Developing FLOs first integrate a yolk sac-like hemogenic endothelium into hepatic endoderm and mesoderm specification. As the hepatic and hematopoietic lineages differentiate, the FLO culture model establishes an autonomous niche capable of driving subsequent progenitor differentiation without exogenous factors. Consistent with yolk sac-derived waves, hematopoietic progenitor cells (HPCs) within FLOs exhibit multipotency with a preference for myeloid lineage commitment, while retaining fetal B and T cell differentiation potential. We reconstruct in FLOs the embryonic monocyte-to-macrophage and granulocyte immune trajectories within the FLO microenvironment and assess their functional responses in the liver niche. In vivo, FLOs demonstrate a liver engraftment bias of hematopoietic cells, recapitulating a key phenomenon of human hematopoietic ontogeny. Our findings highlight the intrinsic capacity of liver organoids to support hematopoietic development, establishing FLOs as a platform for modeling and manipulating human blood-liver niche interactions during critical stages of development and disease.

Background : Many studies have reported on the relationship between cognitive and masticatory functions. However, it remains unclear how the mandibular movements change during chewing in facility residents as dementia progresses. This study aimed to investigate the relationship between a kinematic analysis of mandibular movement during mastication and cognitive function in facility residents. Methods: Sixty-three participants were included from two long-term care facilities. The primary outcome variable was the kinematic data of mandibular movement during mastication. The participants chewed rice crackers, and their faces were recorded during this motion. The partial correlation coefficient between kinematic data and cognitive function was calculated. Furthermore, group comparisons were performed after dividing the participants into three groups based on their cognitive function. Results: Circular motion frequency was significantly correlated with the ABC dementia scale, even after adjusting for the appendicular skeletal muscle index, Eichner index, and short-form mini-nutritional assessment. The cycle and circular motion frequencies were markedly lower in the severe dementia group than in the mild dementia group. Conclusions: With declining cognitive function, mandibular movements during mastication decrease in circular motion and increase in linear motion. Additionally, our results suggested that residents with severe cognitive impairment had more linear mandibular motions during mastication than those with mild cognitive impairment. This may make it more difficult for residents with cognitive decline to ingest normal solid foods.

Treating disseminated cryptococcosis in people with human immunodeficiency virus (HIV) is challenging due to the limited availability of effective antifungals. Although isavuconazole has antifungal activity against Cryptococcus neoformans, clinical evidence is sparse because this new drug has not been approved for the treatment of cryptococcosis in the US or Europe. Here, we report a case of HIV-associated cryptococcal meningitis that relapsed during maintenance therapy with fluconazole. A Japanese man in his 20s was diagnosed with HIV-1 infection and cryptococcal meningitis. The patient was intolerant to flucytosine and was treated with liposomal amphotericin B monotherapy for 2 weeks as induction therapy, followed by fluconazole (400 mg/day) for 3 months as consolidation therapy. Four months after starting maintenance therapy with fluconazole (200 mg/day), the patient presented with fever and cough, leading to readmission to our hospital. Biopsies of a nodule in the left lung and a left cervical lymph node led to the diagnosis of disseminated cryptococcosis (pulmonary cryptococcosis and cryptococcal lymphadenitis). Although a combination of fluconazole and liposomal amphotericin B was ineffective, the patient was successfully treated with an induction therapy combining isavuconazole and liposomal amphotericin B, followed by a maintenance therapy with isavuconazole. The patient received isavuconazole orally except for loading doses, achieving stable blood concentration levels. Moreover, we observed that blood levels of amphotericin B increased gradually with repeated administration. Therefore, isavuconazole may have a potential role in the treatment of cryptococcosis, and clinical trials involving larger numbers of cases are needed to confirm its efficacy and safety., (Copyright © 2024 Japanese Society of Chemotherapy, Japanese Association for Infectious Diseases, and Japanese Society for Infection Prevention and Control. Published by Elsevier Ltd. All rights reserved.)

Purpose: Blood flow signals (BFSs) through the bone cortex on ultrasonography (US) and bone marrow lesions (BMLs) detected on magnetic resonance imaging (MRI) can be used to assess bone lesions; however, no studies have reported their relationship. Therefore, this study aimed to assess whether BFSs through the bone cortex on US can serve as a screening test for detecting BMLs on MRI in patients with early knee osteoarthritis (OA)., Methods: This study enrolled patients with knee joint pain who were diagnosed with early knee OA between January 2018 and January 2024. We targeted 77 patients who underwent MRI and in whom the presence or absence of BFSs through the bone cortex was confirmed on US. The association between BFSs and BMLs was evaluated using the chi-square test, and the sensitivity and specificity of BFSs for detecting BMLs on MRI were calculated., Results: The chi-square test showed that BFSs and BMLs were significantly associated in the femur and tibia (femur: χ 2 [1] = 52.9, p < 0.001; Tibia: χ 2 [1] = 44.8, p < 0.001). The sensitivity, specificity, positive predictive value, and negative predictive value of BFSs for detecting BMLs on MRI were 85.0%, 96.5%, 89.5%, and 94.8%, respectively, for the femur, and 84.0%, 92.3%, 84.0%, and 92.3%, respectively, for the tibia., Conclusion: BFSs through the bone cortex on US can be used as a screening test for detecting BMLs on MRI in patients with early knee OA., (© 2024. The Author(s), under exclusive licence to The Japan Society of Ultrasonics in Medicine.)

A compact, multi-channel ionic liquid-gated graphene field-effect transistor (FET) has been proposed and developed in our work for on-field continuous monitoring of nitrate nitrogen and other nitrogen fertilizers to achieve sustainable and efficient farming practices in agriculture. However, fabricating graphene FETs with easy filling of ionic liquids, minimal graphene defects, and high process yields remains challenging, given the sensitivity of these devices to processing conditions and environmental factors. In this work, two approaches for the fabrication of our graphene FETs were presented, evaluated, and compared for high yields and easy filling of ionic liquids. The process difficulties, major obstacles, and improvements are discussed herein in detail. Both devices, those fabricated using a 3 μm-thick CYTOP ® layer for position restriction and volume control of the ionic liquid and those using a ~20 nm-thick photosensitive hydrophobic layer for the same purpose, exhibited typical FET characteristics and were applicable to various application environments. The research findings and experiences presented in this paper will provide important references to related societies for the design, fabrication, and application of liquid-gated graphene FETs.

Background: Pulmonary vein isolation (PVI) employing cryoballoon (CB) or contact force-guided radiofrequency (CF-RF) catheter ablation has been established as an effective strategy for managing atrial fibrillation (AF). However, its efficacy in hypertrophic cardiomyopathy (HCM) remains to be further explored., Methods: This retrospective study analyzed 60 consecutive AF patients with HCM (average age 67 ± 10 years; 41 men) who were consecutively admitted to our hospital from January 2014 to December 2022 and underwent initial PVI., Results: The patients were treated with CB (26 patients) or CF-RF (34 patients). Successful PVI was achieved in both groups without significant complications. In the CF-RF group, additional ablations were performed on the cavotricuspid isthmus (14.7% of patients) and the anterior line (2.9%). The CB group benefited from reduced procedural times (93 ± 31 vs. 165 ± 60 min, p < 0.05) and decreased saline irrigation requirements (77.5 ± 31.4 vs. 870 ± 281.9 mL, p < 0.0001). Using a contrast medium was exclusive to the CB group (33.8 ± 4.2 mL). In a 12-month follow-up, the atrial tachyarrhythmia recurrence-free rates in the CB and CF-RF groups were comparable (77% and 76%, respectively; p = 0.63 according to the log-rank test). Notably, pulmonary vein reconnection was prevalent in most (7 out of 8) patients requiring a secondary ablation procedure., Conclusion: PVI is feasible as a strategy for AF in patients with HCM employing either CB or CF-RF techniques. While the recurrence-free rates were comparable in both groups, differences were noted in procedure duration, saline usage, and the need for a contrast medium., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Burkholderia cepacia complex (BCC) encompasses opportunistic pathogen with various clinical manifestations ranging from no symptoms to severe respiratory infections and septicemia. Central nervous system infections caused by BCC are rare. To the best of our knowledge, we present the first reported case of choroid plexitis caused by BCC after severe COVID-19. A 67-year-old woman who had been previously diagnosed with COVID-19 presented with a mild fever and headache. Gadolinium-enhanced T1-weighted brain magnetic resonance imaging showed contrast effects in the right choroid plexus and encapsulated abscess. Gram staining of cerebrospinal fluid revealed the presence of gram-negative rods. Broad-range polymerase chain reaction amplification of 16S ribosomal RNA from the cerebrospinal fluid, followed by sequence analysis, identified BCC; thus, choroid plexitis caused by BCC was diagnosed. After prolonged antimicrobial treatment with a multiantibiotic regimen, the patient recovered completely. This case highlights the importance of long-term therapy with a carefully selected multiantibiotic regimen to achieve complete recovery after BCC infection., Competing Interests: Declarations of competing interest The authors have no competing interests to declare., (Copyright © 2024. Published by Elsevier Ltd.)

Intracellular delivery of biomolecules is a prerequisite for genetic techniques such as recombinant engineering and genome editing. Realizing the full potential of this technology requires the development of safe and effective methods for delivering protein tools into cells. In this study, we demonstrated the spontaneous internalization of exogenous proteins into intact cells and root tissue of whole plants of Arabidopsis thaliana. We termed this internalization phenomenon as protein Delivery Independent of Vehicles or Equipment (DIVE), which efficiently delivered genome engineering proteins including Cre recombinase and zinc-finger nucleases (ZFN) into plant cells. Using protein DIVE, we achieved less toxic protein delivery than electroporation with up to 94% efficiency in Arabidopsis cell culture and 19% genome modification in Arabidopsis plants that was maintained in regenerated tissue. This work illustrates the potential of protein DIVE for a wide range of applications, including genome engineering in plants., (© 2024. The Author(s).)

Objective: Water is an essential nutrient for all organisms and is important for maintaining life and health. We aimed to develop a biomarker-calibrated equation for predicting water turnover (WT) and pre-formed water (PW) using the doubly labelled water (DLW) method., Design: Cross-sectional study., Setting: General older population from the Kyoto-Kameoka Study, Japan., Participants: The 141 participants aged ≥ 65 years were divided into a model developing ( n 71) and a validation cohort group ( n 70) using a random number generation. WT and PW was measured using the DLW method in May-June of 2012. In developing the cohort, equations for predicting WT and PW were developed by multivariate stepwise regression using all data from the questionnaires in the Kyoto-Kameoka study (including factors such as dietary intake and personal characteristics). WT and PW measured using the DLW method were compared with the estimates from the regression equations developed using the Wilcoxon signed-rank test and correlation analysis in validation cohort., Results: The median WT and PW for 141 participants were 2·81 and 2·28 l/d, respectively. In the multivariate model, WT ( R 2 = 0·652) and PW ( R 2 = 0·623) were moderately predicted using variables, such as height, weight and fluid intake from beverages based on questionnaire data. WT ( r = 0·527) and PW ( r = 0·477) predicted that using this model was positively correlated with the values measured by the DLW method., Conclusions: Our results showed factors associated with water requirement and indicated a methodological approach of calibrating the self-reported dietary intake data using biomarkers of water consumption.

Introduction: Lenvatinib (LEN) is the standard treatment for hepatocellular carcinoma (HCC). In clinical practice, gastrointestinal (GI) symptoms such as fatigue and loss of appetite often lead to dose reduction or treatment discontinuation. This study aimed to identify the predictors of patients who will experience dose reduction or treatment discontinuation owing to fatigue or GI symptoms during LEN treatment for HCC., Methods: We retrospectively identified 99 patients who received LEN at the Ogaki Municipal Hospital (Ogaki, Japan) between April 2018 and December 2023. To investigate the risk factors for treatment discontinuation or dose reduction due to fatigue or GI symptoms during LEN administration, patients were divided into two groups based on whether treatment discontinuation or dose reduction occurred due to fatigue or GI symptoms during LEN administration (37 patients) or not (62 patients). We compared baseline characteristics between the two groups., Results: Multivariate analysis revealed that body weight (odds ratio 4.310, 95% confidence interval 1.380-13.500; P = 0.002) was an independent risk factor that significantly contributed to treatment discontinuation or dose reduction owing to fatigue or GI symptoms during LEN administration. The cut-off value calculated using the body weight curve was 55.0 kg. Using this cutoff value, the sensitivity and specificity of body weight to detect treatment discontinuation or dose reduction due to fatigue or GI symptoms during LEN administration were 83.9% and 56.8%, respectively., Conclusion: In clinical practice, patients weighing less than 55 kg who start with a full dose will likely experience weight loss or discontinuation during treatment., Competing Interests: Declaration of conflicting interestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Schizophrenia often involves persecutory delusions, which cause psychological distress. Some patients use online gaming as a coping tool. However, excessive online gaming has raised concerns about internet gaming disorders (IGD), while any soothing effects of online gaming on psychological distress remain unclear. Herein, we report changes in anxiety and IGD severity, measured using rating scales, in a patient with schizophrenia who used online gaming as a coping strategy for psychological distress., Case Presentation: A 43-year-old woman diagnosed with schizophrenia had worsening persecutory delusions, including that of being targeted by snipers, and had difficulty going out because of anxiety. She coped with her psychological distress using online shooting games. We assessed her state and trait anxiety, social anxiety, avoidance behavior when alone, and IGD severity. There was a notable reduction in the state anxiety score after the introduction of online gaming. The scores for trait anxiety, social anxiety, and avoidance behavior when alone decreased noticeably after the acquisition of coping strategies. This case demonstrates the presence of IGD only during the acquisition of coping strategies., Conclusion: This case highlights the potential of online gaming as a coping strategy for schizophrenia-related anxiety. However, excessive gaming can lead to IGD and thus necessitates caution. Further research should explore the applicability and potential risks of using online gaming to cope with psychological distress among patients with schizophrenia., Competing Interests: The authors declare that they have no conflict of interest., (© 2024 The Author(s). Psychiatry and Clinical Neurosciences Reports published by John Wiley & Sons Australia, Ltd on behalf of Japanese Society of Psychiatry and Neurology.)

Background: Citrate-related hypocalcemia is the most common adverse event linked with peripheral blood progenitor cell apheresis. A previous retrospective study highlighted the prophylactic effectiveness of oral calcium drinks before apheresis, supplemented with intravenous calcium gluconate. Consequently, this study is a randomized controlled trial comparing oral calcium with placebo drinks STUDY DESIGN AND METHODS: Healthy donors were randomized to receive either oral calcium (Cohort A) or placebo (Cohort B) drinks. If symptoms emerged, all donors were given calcium drinks to counteract hypocalcemia. The primary endpoint centered on the incidence of Grade 1 or higher citrate-related symptoms. Analyses were performed using the crude model and doubly robust estimation., Results: Forty-two healthy donors participated from January 2021 to July 2022. Case distribution (Cohort A: Cohort B) stood at 3:7 (Grade 1), 2:2 (Grade 2), and 1:0 (Grade 3); no Grade 4 cases were identified. There was no statistical significance in the incidence of Grade 1 or higher and Grade 3 citrate-related symptoms., Discussion: The cumulative incidence of citrate-related side effects was less pronounced than in the previous research. This could stem from absence of blinding, and the decision to administer calcium drinks to the untreated group upon symptom detection. Although preemptive oral calcium intake before peripheral blood progenitor cell apheresis is not wholly effective, providing calcium-rich beverages to symptomatic donors may stave off symptom intensification., Competing Interests: Conflicts of interest The authors report no declarations of interest., (Copyright © 2024 Associação Brasileira de Hematologia, Hemoterapia e Terapia Celular. Published by Elsevier España, S.L.U. All rights reserved.)

Objective: Usage of time in range (TIR), measured by continuous glucose monitoring (CGM), has become common as a new index of glycemic control. Therefore, we compared points in range (PIR), measured by the self-monitoring of blood glucose (SMBG), with TIR., Methods: In this prospective observational study, 43 patients with diabetes wore FreeStyle Libre Pro and conducted SMBG at the same time. Time above range (TAR), TIR, time below range (TBR) and points above range (PAR), PIR, points below range (PBR) were compared, respectively., Results: The median PAR was 35.7%, while the median TAR was 20.8% for CGM. Conversely, the PIR was 64.3%, while the TIR was 74.9%; similarly, the PBR was 0%, while the TBR was 1.7%. A significant positive correlation was found between PIR and TIR (r = 0.784, P < 0.001). In the Bland-Altman analysis performed to assess the association between the two methods, PIR showed a -9.9% bias compared with TIR., Conclusions: PIR may be used in patients who find it difficult to use CGM as a substitute of TIR, however caution is needed when interpreting the data due to the difference between PIR and TIR.

Ryugu is the C-type asteroid from which material was brought to Earth by the Hayabusa2 mission. A number of individual grains and fine-grained samples analysed so far for noble gases have indicated that solar wind and planetary (known as P1) noble gases are present in Ryugu samples with concentrations higher than those observed in CIs, suggesting the former to be more primitive compared to the latter. Here we present results of analyses of three fine-grained samples from Ryugu, in one of which Xe concentration is an order of magnitude higher than determined so far in other samples from Ryugu. Isotopically, this Xe resembles P1, but with a much stronger isotopic fractionation relative to solar wind and significantly lower 36 Ar/ 132 Xe ratio than in P1. This previously unknown primordial noble gas component (here termed P7) provides clues to constrain how the solar composition was fractionated to form the planetary components., (© 2024. Crown.)

An 83-year-old woman presented with disturbance of consciousness and hand tremor. She had taken lithium carbonate 300 mg/day for bipolar disorder and magnesium oxide 660 mg/day for constipation. Blood tests revealed lithium poisoning, hypermagnesemia and acute kidney injury. Computed tomography showed colonic obstruction caused by cancer of the descending colon. In the outpatient section, her blood pressure decreased to 89/54 mmHg, and her heart rate dropped to 40 bpm. We considered that the obstructive ileus induced intravascular dehydration, which led to toxic serum concentrations of lithium and magnesium, triggering the emergence of severe arrythmia induced by sinus dysfunction. The patient was treated with fluid resuscitation and hemodialysis, followed by endoscopic stent replacement for the descending colon cancer obstruction. These treatments improved her general condition and alleviated the lithium poisoning, hypermagnesemia and colonic obstruction. Such a case is considered extremely rare., Competing Interests: We have no conflict of interest to declare., (© The Author(s) 2024. Published by Oxford University Press.)

Background Psychological state has been reported as one of the factors strongly related to a return to sports after anterior cruciate ligament (ACL) reconstruction. However, its relationship with the emotional state remains unclear. The aim of this study was to investigate whether patients who have undergone ACL reconstruction and have a higher preoperative psychological competitive ability have a better emotional status preoperatively and six months postoperatively. Methods Patients with a Tegner activity score of ≥6 who underwent ACL reconstruction between 2015 and 2020 were divided into two groups according to their grades on the Diagnostic Inventory of Psychological Competitive Ability for Athletes (DIPCA.3). The emotional states preoperatively and at six months postoperatively were assessed using the Profile of Mood States Second Edition (POMS2) and compared between the two groups. Furthermore, the possibility of returning to sports was compared between the groups based on participation in the entire practice at six months postoperatively. Results Eighty-four patients were included and divided into the high (DIPCA.3 grades ≥4, n = 23) and low (DIPCA.3 <4, n = 61) groups. Vigor-activity and friendliness were significantly higher in the high group than in the low group preoperatively. The difference was even greater at six months after ACL reconstruction. In addition, the high group showed significantly better results postoperatively for fatigue-inertia and total mood disturbance. Rates of return to sports did not differ significantly between the high and low groups (56.5% vs. 54.1%). Conclusions Those with a higher preoperative psychological competitive ability were in a positive emotional state preoperatively and six months after ACL reconstruction. However, the psychological competitive ability did not affect the rate of participation in the entire practice at six months postoperatively., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Ethics Review Committee of Kanazawa University issued approval 2015-058(1860). Animal subjects: All authors have confirmed that this study did not involve animal subjects or tissue. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Sengoku et al.)

Eight peaks of coronavirus disease 2019 (COVID-19) outbreak occurred in Japan, each associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern. The National Epidemiological Surveillance of Infectious Diseases (NESID) analyzed viral genome sequences from symptomatic patients and submitted the results to GISAID. Meanwhile, commercial testing services occasionally sequence samples from asymptomatic individuals. We compared a total of 1248 SARS-CoV-2 full-genome sequences obtained from the SB Coronavirus Inspection Center Corp. (SBCVIC) during Japan's seventh wave, which was dominated by Omicron variants, with 1764 sequences obtained in Japan from GISAID during the same period using chronological phylogenies and molecular transmission networks. The number of SBCVIC sequences was consistent with the number of cases reported by NESID. The SBCVIC detected a shift in the PANGO lineage from BA.2 to BA.5 earlier than that of GISAID. BA.2 lineages from the SBCVIC were distributed at different locations in the transmission network dominated by GISAID entries, whereas BA.5 lineages from SBCVIC and GISAID often formed distinct subclusters. Test-based sentinel surveillance of asymptomatic individuals may be a more manageable approach compared to notifiable disease surveillance; however, it may not necessarily capture all infection populations throughout Japan., (© 2024. The Author(s).)

Background: Pulsed field ablation (PFA), a novel treatment for atrial fibrillation (AF), has yet to be evaluated in a Japanese cohort., Methods: In this sub-analysis of the PULSED AF trial, 12-month outcomes of paroxysmal AF (PAF) and persistent AF (PsAF) patients treated with PFA in four Japan centers were assessed. After a 90-day blanking period, primary efficacy was determined via freedom from a composite endpoint of acute procedural failure, arrhythmia recurrence, or antiarrhythmic drug escalation over 1 year. Patient improvement was evaluated via two quality of life (QoL) surveys (AFEQT and EQ-5D) at baseline and 12 months., Results: The analysis included 32 patients, 16 PAF and 16 PsAF, with PAF patients averaging 61.1 ± 10.6 years and PsAF patients averaging 62.8 ± 11.5 years of age. Females made up 31% of PAF and 25% of PsAF cohorts. Acute pulmonary vein isolation was achieved in 100% of both cohorts. The primary efficacy success rate at 12 months was 75.0% for PAF and 56.3% for PsAF patients. No primary safety events occurred. The mean AFEQT score significantly increased for both PAF (25.9 points, p < 0.0001) and PsAF (13.2 points, p = 0.0002) patients, while the EQ-5D-5L score improved significantly for PAF (0.12 points, p = 0.048) patients but not for PsAF (0.04 points, p = 0.08) patients., Conclusions: Similar to outcomes in the global cohort, ablation with the PulseSelect™ PFA catheter was efficient, effective, and safe in a Japanese population, resulting in improved QoL for PAF and PsAF patients., Clinical Trial Registration: ClinicalTrials.gov Identifier: NCT04198701., (© 2024. The Author(s).)

Background/Objectives : The purpose of this study was to analyze relevant areas in acute-stage fluorescein angiography (FA) images, predicting the long-term visual prognosis of branch retinal vein occlusion (BRVO) based on gradient-weighted class activation mapping (Grad-CAM). Methods : This retrospective observational study included 136 eyes with BRVO that were followed up for more than a year post-FA. Cropped grayscale images centered on the fovea (200 × 200 pixels) were manually pre-processed from early-phase FA at the acute phase. Pairs of the cropped FA images and the best-corrected visual acuity (BCVA) in remission at least one year post-FA were used to train a 38-layer ResNet with five-fold cross-validation. Correlations between the ResNet-predicted and true (actually measured) logMAR BCVAs in remission, and between the foveal avascular zone (FAZ) area measured by ImageJ (version 1.52r) from FA images and true logMAR BCVA in remission were evaluated. The heat maps generated by Grad-CAM were evaluated to determine which areas were consumed as computational resources for BCVA prediction. Results : The correlation coefficient between the predicted and true logMAR BCVAs in remission was 0.47, and that between the acute-stage FAZ area and true logMAR BCVA in remission was 0.42 ( p < 0.0001 for both). The Grad-CAM-generated heat maps showed that retinal vessels adjacent to the FAZ and the FAZ per se had high selectivity (95.7% and 62.2%, respectively). Conclusions : The Grad-CAM-based analysis demonstrated FAZ-neighboring vessels as the most relevant predictor for the long-term visual prognosis of BRVO.

Bovine lactoferrin (bLF) is a 77 kDa glycoprotein that is abundant in bovine breast milk and exerts various bioactive functions, including antibacterial and antiviral functions. Few studies have explored bLF activity against parasites. We found that bLF affects hemozoin synthesis by binding to heme, inhibiting heme iron polymerization necessary for Plasmodium berghei ANKA survival in infected erythrocytes, and also binds to hemozoin, causing it to disassemble. In a challenge test, bLF administration inhibited the growth of murine malaria parasites compared to untreated group growth. To determine whether the iron content of bLF affects the inhibition of malaria growth, we tested bLFs containing different amounts of iron (apo-bLF, native-bLF, and holo-bLF), but found no significant difference in their effects. This indicated that the active sites were located within the bLFs themselves. Further studies showed that the C-lobe domain of bLF can inhibit hemozoin formation and the growth of P. berghei ANKA. Evaluation of pepsin degradation products of the C-lobe identified a 47-amino-acid section, C-1, as the smallest effective region that could inhibit hemozoin formation. This study highlights bLF's potential as a novel therapeutic agent against malaria, underscoring the importance of its non-iron-dependent bioactive sites in combating parasite growth., (© 2024. The Author(s).)

Introduction: This study aimed to evaluate the efficacy and safety of atezolizumab combined with bevacizumab (Atez/Bev) compared to lenvatinib (LEN) as first-line systemic therapy for patients with Barcelona Clinic Liver Cancer (BCLC) stage B hepatocellular carcinoma (HCC) exceeding the up-to-seven criteria threshold, who are typically unsuitable for transarterial chemoembolization (TACE)., Methods: A retrospective analysis was conducted on 49 consecutive patients with HCC treated at Tokyo Metropolitan Komagome Hospital between May 2018 and October 2023. The patients were divided into two groups: the Atez/Bev group (21 patients) and the LEN group (28 patients). Eligibility criteria included Child-Pugh A classification, no prior systemic therapy, and ineligibility for resection, ablation, or transplantation. Treatment outcomes were assessed through periodic imaging and laboratory tests, evaluating OS, PFS, ORR, and disease control rate (DCR)., Results: Both groups demonstrated comparable baseline characteristics, with a median follow-up of 15.4 months. No significant difference was observed in OS between the Atez/Bev and LEN groups (median OS: 19.80 vs. 22.20 months, p = 0.763). The median PFS was 10.23 months for Atez/Bev and 7.20 months for LEN (p = 0.343). There were no statistically significant differences in ORR or DCR between the two groups. Common adverse events included elevated AST and ALT levels, with no significant difference in the overall rate of adverse events between the groups., Conclusions: Atez/Bev and LEN demonstrated comparable efficacy and safety as first-line systemic treatments for patients with BCLC stage B HCC exceeding the up-to-seven criteria. Both therapeutic options are viable for this population, though further large-scale prospective studies are required to confirm these findings., (© 2024 The Author(s). Cancer Medicine published by John Wiley & Sons Ltd.)

Background: Short foot exercise (SFE) can be combined with dynamic functional tasks such as squats; however, it is unclear whether this combination increases intrinsic foot muscle activity., Research Question: This study aimed to investigate and compare the abductor hallucis muscle (AbdH) activity during SFE in static and dynamic functional tasks., Methods: The AbdH electromyography data of 17 healthy participants with and without SFE were analyzed during static tasks (sitting, double-leg standing, and single-leg standing) and dynamic tasks (double-leg squat, single-leg squat, split squat, and heel-raise). The static tasks were performed with SFE for 5 seconds, and the dynamic tasks were performed while performing SFE. AbdH activity with or without SFE during the task was compared using the Friedman and Wilcoxon signed-rank tests., Results: AbdH activity was significantly greater in conditions with SFE than in those without SFE for all tasks (P < 0.01) except for heel-raise (P = 0.163). AbdH activity during SFE in single-leg standing was significantly higher than that in sitting, double-leg standing, and double-leg squats (P < 0.05). AbdH activity during SFE in the single-leg squat was also significantly greater than that in the sitting position (P = 0.024). No significant differences were found in any other between-task comparisons of AbdH activity during SFE. AbdH activity during tasks without SFE revealed significantly lower levels for sitting and double-leg standing compared to single-leg squat, split squat, and heel-raise (P < 0.001). Additionally, the activity in double-leg squat was significantly lower than in both single-leg squat and heel-raise (P < 0.05)., Significance: Combining dynamic tasks, except for the heel-raise task, with SFE can increase AbdH activity more than dynamic tasks without SFE. However, clinicians should note that combining dynamic tasks with the SFE may not increase AbdH activity compared to combining static tasks with the SFE., Competing Interests: Declaration of Competing Interest None declared., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Dementia is a critical late-life health issue that occurs among members of aging societies. This study examined the relationships between eating out, dietary diversity, and mild cognitive impairment (MCI) among community-dwelling older adults., Methods: We analyzed data from 597 older adults (median age 73.0 years, interquartile range 69.0-78.0 years; 62.6% females). We applied the food frequency score to evaluate diet variety and the weekly consumption frequencies of ten food items were determined. The National Center for Geriatrics and Gerontology Functional Assessment Tool (NCGG-FAT) was used to evaluate MCI. Finally, we asked the participants how often they ate out each month; those who replied &quot;none&quot; were categorized into the &quot;non-eating out&quot; group., Results: The overall prevalence of MCI was 122 (20.4%), with a higher prevalence in the low dietary diversity group than in the high dietary diversity group (28.6% vs. 18.6%). After adjusting for covariates, the participants who self-described as not eating out were independently associated with low dietary diversity (odds ratio [OR]=1.97, 95% confidence interval [CI] 1.20-3.20), while low dietary diversity was associated with MCI (OR=1.72; 95% CI 1.02-2.87). Structural equation models revealed that not eating out had no direct effect on MCI but was associated with MCI via low dietary diversity (root mean square error of approximation=0.030, goodness-of-fit index=0.999, and adjusted goodness-of-fit index=0.984)., Conclusions: Although non-eating out may not have a direct effect on MCI, an indirect relationship may exist between eating-out habits and MCI via dietary diversity status.

Background: A left ventricular assist device (LVAD) is an effective therapeutic option for advanced heart failure. Late right heart failure (LRHF) is a complication after LVAD implantation that is associated with increasing morbidity and mortality; however, the assessment of right heart function, including right heart reserve function after LVAD implantation, has not been established. We focused on a fluid-loading test with right heart catheterization to evaluate right heart preload reserve function and investigate its impact on LRHF., Methods: Patients aged > 18 years who received a continuous-flow LVAD between November 2007 and December 2022 at our institution, and underwent right heart catheterization with saline loading (10 mL/kg for 15 minutes) 1 month after LVAD implantation, were included., Results: Overall, 31 cases of LRHF or death (right heart failure [RHF] group) occurred in 149 patients. In the RHF vs the non-RHF groups, the pulmonary artery pulsatility index (PAPi) at rest (1.8 ± 0.89 vs 2.5 ± 1.4, P = 0.02) and the right ventricular stroke work index (RVSWi) change ratio with saline loading (0.96 ± 0.32 vs 1.1 ± 0.20, P = 0.03) were significantly different. The PAPi at rest and the RVSWi change ratio with saline loading were identified as postoperative risks for LRHF and death. The cohort was divided into 3 groups based on whether the PAPi at rest and the RVSWi change ratio were low. The event-free curve differed significantly among the 3 groups (P < 0.001)., Conclusions: Hemodynamic assessment with saline loading can evaluate the right ventricular preload reserve function of patients with an LVAD. A low RVSWi change with saline loading was a risk factor for LRHF following LVAD implantation., (Copyright © 2024 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.)

The purpose of the study was to investigate the relationship between diffusion tensor imaging (DTI) and the clinical classification of cubital tunnel syndrome (CuTS). Ten patients with CuTS (7 men and 3 women; mean age: 52.7 years) and 5 patients without ulnar neuropathy (2 men and 3 women; mean age: 38.0 years) were enrolled in this retrospective study. Fifteen patients were clinically classified into three groups: "Normal", "1 and 2A", and "2B and 3" by an orthopedic surgeon using the modified McGowan stages. DTI was acquired using a 3.0-T MRI. Fractional anisotropy (FA) of the ulnar nerve was measured in slices covering 20 mm proximal to 20 mm distal to ulnar sulcus. Median FA values in each group were compared by Kruskal-Wallis and Steel-Dwass test (P < 0.05). Five patients with CuTS were classified as "1 and 2A" and five patients as "2B and 3". The FA values, proximal 12 mm to the ulnar sulcus were 0.486 ± 0.117, 0.425 ± 0.166 and 0.298 ± 0.0386 in the "Normal", "1 and 2A" and "2B and 3" groups, respectively. The FA values of patients classified as "Normal" were significantly higher than those classified as "2B and 3" (P = 0.0326 in Steel-Dwass test). FA proximal to the ulnar sulcus might be associated to the modified McGowan stages for the clinical classification of CuTS., (© 2024. The Author(s), under exclusive licence to Japanese Society of Radiological Technology and Japan Society of Medical Physics.)

The most common toxicities associated with cyclin-dependent kinase (CDK) 4/6 inhibitor therapy include decreased leukopenia and neutropenia due to the inhibition of CDK6 of leukocyte and neutrophil precursors in bone marrow. These hematological toxicities are more commonly observed with palbociclib administration than with abemaciclib administration, which is approximately 13 times more selective against CDK4 than CDK6. Thus, even though both successfully inhibit CDK4/6, the side effects of palbociclib and abemaciclib differ due to differences in selectivity. Recent reports have suggested an association between palbociclib and medication-related osteonecrosis of the jaw; however, reports on this association are inconsistent. This study investigated the potential association of palbociclib and abemaciclib with MRONJ using the FAERS. Signals of "Osteonecrosis of jaw" were detected only in females using palbociclib (cROR 025 : 2.08). Other signals detected included stomatitis-related adverse events with abemaciclib and intraoral soft tissue damage and infection with palbociclib. As previous exploratory studies have reported MRONJ signals for bisphosphonates and denosumab, we calculated the aROR for palbociclib-induced osteonecrosis of the jaw using concomitant bisphosphonates and denosumab as covariates. A signal was detected even after adjusting for sex, age, and concomitant medications as covariates (aROR0 025 : 5.74). A proper understanding of the differences in CDK selectivity is necessary for the appropriate use of CDK4/6 inhibitors. To the best of our knowledge, this is the first report on CDK4/6 inhibitors and drug-related osteonecrosis of the jaw. We believe that these results will offer new insights into adverse events related to the use of CDK4/6 inhibitors, and may aid in the proper use of CDK4/6 inhibitors., (© 2024 UICC.)

Competing Interests: The authors declare that they have no conflict of interest.

The effect of trivalent cation Fe 3+ on the gelation process of a sodium salt form of gellan (DG, deacylated gellan gum) was investigated by rheology and DSC studies. On addition of a fairly low concentration of Fe 3+ (1 mM), both the complex modulus (G*) of a 1.0 % DG solution in gel state and the sol-gel transition temperature (T gel ) slightly decreased. At higher Fe 3+ concentrations (2 and 3 mM), however, a slight increase in the G* and T gel was observed. In the coexisting monovalent cation (K + ) solutions, addition of Fe 3+ always improved the G* in gel state and the T gel in a concentration-dependent manner. Moreover, for all Fe 3+ DG solutions, the ordered structure formation temperature (T order ) was always lower than T gel and increased with increasing Fe 3+ concentration. This finding indicates that the network formation in the DG solutions should occur in advance of the ordered structure formation of the DG chains and that the presence of Fe 3+ unfavorably affected the conformational transition of DG. In coexisting cation solution, the presence of K + ion made a favorable contribution to the binding of Fe 3+ to the disordered DG chains and to the subsequent ordered structure formation of the DG chains., 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.)

Background: Appropriate adverse event (AE) management and maintenance of therapeutic intensity are necessary to achieve therapeutic benefits of CDK4/6 inhibitors (palbociclib and abemaciclib) in hormone receptor-positive, HER2-negative metastatic/recurrent breast cancer. Objective: This study was aimed at clarifying the effect of AEs associated with palbociclib and abemaciclib on treatment. Methods: A total of 62 and 49 patients were prescribed palbociclib and abemaciclib, respectively, at our hospital from January 1, 2018 to June 30, 2023. The rate and reasons for treatment discontinuation, interruption of administration, and changes in dose and dosing schedule, treatment duration, and relative dose intensity (RDI) were compared between the groups of patients prescribed the 2 treatments. Results: Treatment discontinuation due to AEs occurred more frequently with abemaciclib (12 patients) because of interstitial lung disease and hepatic and renal events than with palbociclib (5 patients; P = .008). Administration was interrupted in 57 (91.9%) and 35 (71.4%) patients treated with palbociclib and abemaciclib, respectively ( P = .004). Dose reduction occurred in 37 (67.3%) and 19 (47.5%) patients treated with palbociclib and abemaciclib, respectively ( P = .053). The median [range] treatment duration was 301 [21-1643] days for palbociclib and 238 [70-1526] days for abemaciclib (log-rank test, P = .581). The median RDI was 59.7% and 59.6% for palbociclib and abemaciclib, respectively ( P = .539). Although the AEs of palbociclib and abemaciclib affected the treatment considerably, the treatment duration and RDI were similar. Conclusion: CDK4/6 inhibitors should be selected based on the tolerability and manageability of each AE., 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.

Human granulocytic anaplasmosis (HGA) is a tick-borne infection caused by Anaplasma phagocytophilum. Only seven cases of HGA have been reported in Japan to date. We report the case of a 61-year-old female farmer who developed HGA with rash and rhabdomyolysis. The patient had fever and erythema covering the entire body, including the palms. An induration with an eschar was observed on the right leg, indicating that the patient had been bitten by a tick. Elevated serum creatinine and creatinine kinase levels and hematuria indicated rhabdomyolysis. We suspected Japanese spotted fever, a tick-borne illness caused by Rickettsia Japonica, and administered minocycline and ciprofloxacin for a week. Transient neutropenia and thrombocytopenia were observed, but the symptoms improved. Polymerase chain reaction (PCR) and antibody tests for R. japonica and Orientia tsutsugamushi, which causes scrub typhus, were both negative. The PCR test for severe fever with thrombocytopenia syndrome virus was also negative. Antibodies against A. phagocytophilum-related proteins were detected by western blotting, indicating seroconversion of IgG with paired serum samples, and the patient was diagnosed with HGA. HGA should be suspected in acute febrile patients with a history of outdoor activity and cytopenia, with or without a rash. A testing system and the accumulation of cases in Japan are necessary for the early diagnosis and appropriate treatment of HGA., (Copyright © 2024 Japanese Society of Chemotherapy, Japanese Association for Infectious Diseases, and Japanese Society for Infection Prevention and Control. Published by Elsevier Ltd. All rights reserved.)

Objectives: Long-term care (LTC) residents are susceptible to falling and the risk of subsequent morbidity and mortality may be compounded with concurrent anticoagulation use. Uncertainty exists around the benefit and harm of anticoagulation use for residents with a high risk for falls because of concerns of major bleeding complications. We aimed to examine if anticoagulant use increases mortality risk among LTC residents who fall., Design: A retrospective cohort study., Setting and Participants: Older adults (≥65 years) admitted to a LTC facility in Ontario, Canada between January 1, 2010, and December 1, 2019, who were transferred to emergency departments for fall-related injuries., Methods: The exposure was the use of an oral anticoagulant (OAC). The primary outcome was mortality within 30 days of transfer. Secondary outcomes were major hemorrhage and care utilization. We used hierarchical logistic regression models to examine the association between the use of OAC and 30-day mortality., Results: There were 56,419 residents transferred to the hospital for a fall, of whom 9611 (17.0%) were on an OAC. At 30 days, 5794 (10.3%) of the cohort had died: 12.0% (1151) on an OAC and 9.90% (4643) not on an OAC [risk difference (RD), 2.1%; 95% CI, 1.40%-2.82%]. There were 485 major hemorrhage cases: 1.3% (125) on an OAC and 0.8% (360) not on an OAC (RD, 0.5%; 95% CI, 0.26%-0.74%). Multivariable analysis found no significant association between OAC use and 30-day mortality [odds ratio (OR), 0.98; 95% CI, 0.90-1.06], but an increased risk of major hemorrhage (OR, 1.31; 95% CI, 1.04-1.66). Both groups had similar health system and neurosurgical care utilization., Conclusions and Implications: Among LTC residents transferred to the emergency department for fall-related injuries, OACs did not increase the risk of post-fall mortality. OAC prescribing for frail older adults who experience falls should consider their individual risk profile., Competing Interests: Disclosures The authors declare no conflicts of interest., (Copyright © 2024 Post-Acute and Long-Term Care Medical Association. Published by Elsevier Inc. All rights reserved.)

Most elements of filamentous fungi seen in human tissue by pathologists are hyphae, and encountering other elements may interfere with diagnosis. Sporangia and chlamydospores are such elements that have been described in only a few case reports. We present an autopsy case with the extremely rare coexistence of Mucorales sporangia and chlamydospores in the lung. These fungal elements must be recognized and identified accurately because they can easily be mistaken for other fungi, microorganisms, or degenerated tissue structures., (© 2024 Japanese Society of Pathology and John Wiley & Sons Australia, Ltd.)

In the case of adenosine-sensitive atrial tachycardia originating near the atrioventricular (AV) node, overdrive pacing from the anterior right atrium showed constant and progressive fusion, indicating that the pacing site is proximal to slow conduction. Shortening the pacing cycle length prolonged conduction times to the orthodromic capture sites; they remained unchanged at the antidromic capture sites. Limited decremental conduction property in the slow conduction zone supports the hypothesis that AV node-like tissue remnants along the AV annulus are involved., Competing Interests: Dr. Masaomi Kimura is an associate professor of the Department of Advanced Management of Cardiac Arrhythmias, which is an endowment department supported by Medtronic Japan Co., Ltd., and Fukuda Denshi Kita‐Tohoku Hanbai Co., Ltd. Dr. Hirofumi Tomita is a concurrent professor of the Department of Advanced Management of Cardiac Arrhythmias and also received a research grant from Abbott Medical Japan LLC. Other authors have no relevant disclosures., (© 2024 The Author(s). Journal of Arrhythmia published by John Wiley & Sons Australia, Ltd on behalf of Japanese Heart Rhythm Society.)

We investigate a physical characterization of the gradient flow structure of variational fracture models for brittle materials: a Griffith-type fracture model and an irreversible fracture phase field model. We derive the Griffith-type fracture model by assuming that the fracture energy in Griffith's theory is an increasing function of the crack tip velocity. Such a velocity dependence of the fracture energy is typically observed in polymers. We also prove an energy dissipation identity of the Griffith-type fracture model, in other words, its gradient flow structure. On the other hand, the irreversible fracture phase field model is derived as a unidirectional gradient flow of a regularized total energy. We have considered the time relaxation parameter a mathematical approximation parameter, which we should choose as small as possible. In this research, however, we reveal the physical origin of the gradient flow structure of the fracture phase field model (F-PFM) and show that the small time relaxation parameter is characterized as the rate of velocity dependence of the fracture energy. It is verified by comparing the energy dissipation properties of those two models and by analysing a travelling wave solution of the irreversible F-PFM. This article is part of the theme issue 'Non-smooth variational problems with applications in mechanics'.