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Electron transfers in multinuclear metal complexes are the origin of their unique functionalities both in natural and artificial systems. However, electron transfers in multinuclear metal complexes are generally complicated, and predicting and controlling these electron transfers is extremely difficult. Herein, we report the precise manipulation of the electron transfers in multinuclear metal complexes. The development of a rational synthetic strategy afforded a series of pentanuclear metal complexes which composed of metal ions and 3,5-bis(2-pyridyl)pyrazole (Hbpp) as a platform to probe the phenomena. Electrochemical and spectroscopic investigations clarified overall picture of the electron transfers in the pentanuclear complexes. In addition, unique electron transfer behaviors, in which the reduction of a metal center occurs during the oxidation of the overall complex, were identified. We also elucidated the two dominant factors that determine the manner of the electron transfers. Our results provide comprehensive guidelines for interpreting the complicated electron transfers in multinuclear metal complexes., (© 2024 The Authors. Angewandte Chemie International Edition published by Wiley-VCH GmbH.)

Background: Tailored, preventive cancer care requires the identification of pathogenic germline variants (PGVs) among potentially at-risk blood relatives (BRs). Cascade testing is carried out for BRs of probands who are positive for PGVs of an inherited cancer but not for negative probands. This study was conducted to examine the prevalence of PGVs for BRs of PGV-negative probands., Methods: PGV prevalence was assessed for 682 BRs of 281 probands with BRCA1/BRCA2 wild-type hereditary breast and ovarian cancer (HBOC) syndrome., Results: PGVs were discovered in 22 (45.8%) of the 48 BRs of the PGV-positive probands and in 14 (2.2%) of 634 BRs of the PGV-negative probands. Eleven PGVs on high-risk BRCA1, BRCA2, and TP53 genes were present only in BRs and not in the probands (probands vs BRs in Fisher exact test; p = 0.0104; odds ratio [OR] = 0.000 [0.000-0.5489 of 95% confidence interval]), partly due to the nature of the selection criteria. The enrichment of high-risk PGVs among BRs was also significant as compared with a non-cancer East Asian population (p = 0.0016; OR = 3.0791 [1.5521-5.6694]). PGV prevalence, risk class of gene, and genotype concordance were unaffected by the cancer history among BRs., Conclusion: These findings imply the necessity to construct a novel testing scheme to complement cascade testing., (© 2024. The Author(s).)

In recent years, reported cases of salmonellosis in cattle and horses in Hokkaido, Japan, have increased. To optimize antimicrobial therapy, we assessed the antimicrobial susceptibility of Salmonella isolates from these animals. Among 112 bovine isolates, high resistance rates were observed for streptomycin (92.0%), ampicillin (88.4%), and tetracycline (79.5%), while resistance rates for kanamycin (8.9%), ciprofloxacin (1.8%), gentamicin (0.0%), and colistin (0.0%) were low. Additionally, 18.8% of the bovine isolates were resistant to cefotaxime, and all of these cefotaxime-resistant isolates carried bla CMY-2 . Among 16 equine isolates, no resistance was observed to cefazolin, cefotaxime, gentamicin, nalidixic acid, ciprofloxacin, colistin, or chloramphenicol. Gentamicin and kanamycin are recommended as the first-line treatment for salmonellosis in cattle, with fluoroquinolones as the second choice.

Fear of cancer recurrence (FCR) is a common and distressing condition among adolescents and young adults (AYAs). This study aims to investigate the efficacy of digital interventions, including distress screening-based information provision and smartphone problem-solving therapy, on common psychological distress, especially FCR, in AYA patients with cancer. Participants will be 224 AYA outpatients with cancer aged 15-39 years who will be randomly assigned to either an 8-week smartphone-based intervention or a waitlist control group. This intervention includes smartphone-based distress screening, information provision, and psychotherapy (problem-solving therapy). The primary endpoint will be the Fear of Cancer Recurrence Inventory-Short Form score at week 8. This study will be conducted as a fully decentralized, randomized, and multicenter trial. The study protocol was approved by the Institutional Review Board of Nagoya City University on 19 April 2024 (ID: 46-23-0005). Trial registration: UMIN-CTR: UMIN000054583., (© The Author(s) 2024. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: This study aimed to clarify the effects of exercise-based cardiac rehabilitation (CR) on patients with heart failure., Methods and Results: Patients were divided into groups according to intervention duration (<6 and ≥6 months). We searched for studies published up to July 2023 in Embase, MEDLINE, PubMed, and the Cochrane Library, without limitations on data, language, or publication status. We included randomized controlled trials comparing the efficacy of CR and usual care on mortality, prehospitalization, peak oxygen uptake (V̇O 2 ), and quality of life. Seventy-two studies involving 8,495 patients were included in this review. It was found that CR reduced the risk of rehospitalization for any cause (risk ratio [RR] 0.80; 95% confidence interval [CI] 0.70-0.92) and for heart failure (RR 0.88; 95% CI 0.78-1.00). Furthermore, CR was found to improve exercise tolerance (measured by peak V̇O 2 and the 6-min walk test) and quality of life. A subanalysis performed based on intervention duration (<6 and ≥6 months) revealed a similar trend., Conclusions: Our meta-analysis showed that although CR does not reduce mortality, it is effective in reducing rehospitalization rates and improving exercise tolerance and quality of life, regardless of the intervention duration.

This study investigated the potential of the metaverse in providing psychological support for pediatric and AYA cancer patients, with a focus on those with rare cancers. The research involved ten cancer patients and survivors from four distinct regions in Japan, who participated in metaverse sessions using customizable avatars, facilitating interactions across geographical and temporal barriers. Surveys and qualitative feedback were collected to assess the psychosocial impact of the intervention. The results demonstrated that the metaverse enabled patients to connect with peers, share experiences, and receive emotional support. The anonymity provided by avatars helped reduce appearance-related anxiety and stigma associated with cancer treatment. A case study of a 19-year-old male with spinal Ewing's sarcoma highlighted the profound emotional relief fostered by metaverse interactions. The findings suggest that integrating virtual spaces into healthcare models can effectively address the unique needs of pediatric and AYA cancer patients, offering a transformative approach to delivering psychosocial support and fostering a global patient community. This innovative intervention has the potential to revolutionize patient care in the digital age.

The lateral amygdala (LA) encodes fear memories by potentiating sensory inputs associated with threats and, in the process, recruits 10-30% of its neurons per fear memory engram. However, how the local network within the LA processes this information and whether it also plays a role in storing it are still largely unknown. Here, using ex vivo 12-patch-clamp and in vivo 32-electrode electrophysiological recordings in the LA of fear-conditioned rats, in combination with activity-dependent fluorescent and optogenetic tagging and recall, we identified a sparsely connected network between principal LA neurons that is organized in clusters. Fear conditioning specifically causes potentiation of synaptic connections between learning-recruited neurons. These findings of synaptic plasticity in an autoassociative excitatory network of the LA may suggest a basic principle through which a small number of pyramidal neurons could encode a large number of memories., (© 2024. The Author(s).)

Background: Self-expandable metallic stent (SEMS) was introduced for the treatment of obstructive colorectal cancer (CRC) a few decades ago. However, its long-term outcomes remain controversial, especially for stage IV CRC. The aim of this study was to clarify the outcomes of SEMS as a "bridge to surgery" (BTS) for obstructive and symptomatic primary tumors in stage IV CRC by one-to-one propensity-score matching. Materials and Methods: This retrospective cohort study was conducted at a single center from January 2007 to December 2017. Patients with obstructive and symptomatic primary tumors of stage IV CRC underwent primary resection (PR) or placement of a SEMS as a BTS. They were divided into SEMS and PR groups, and their short- and long-term outcomes were compared. Results: In total, 52 patients were reviewed (SEMS group, 21; PR group, 31). Sixteen patients in both groups were matched using propensity scores. Patients in the SEMS group more frequently underwent laparoscopic surgery than those in the PR group (75% versus 19%, P  = .004). The two groups showed no significant differences in perioperative and pathological outcomes. The 5-year overall survival was not significantly different between groups (29% versus 20%, P  = .53). Conclusions: As a BTS, the use of SEMS for obstructive and symptomatic primary tumors in CRC stage IV can be a comparable option to PR in terms of short- and long-term outcomes, and would be less invasive with respect to surgical procedures.

The increasing number of treatment options for patients with mantle cell lymphoma (MCL) and chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) in Japan underscores the critical need to comprehend their treatment preferences. In this study, individual semi-structured interviews with 20 Japanese patients with diagnosis of MCL or CLL/SLL were conducted and qualitatively analyzed to elicit concepts important for patients regarding treatment selection. Although effectiveness and safety were imperative for treatment selection, convenience and quality of life were also reported as important attributes. Over the course of their disease journey, patients reported diverse and changing preferences in terms of treatment characteristics. Additionally, there was a discrepancy between their desired and actual levels of involvement in shared decision-making with physicians about treatment choices. Optimal personalized care for better outcomes of patients with MCL and CLL/SLL hinges on healthcare professionals acknowledging individual patient needs and preferences within their cultural, societal and personal context.

Purpose: This study investigated the effects of ice cream consumption on chyle leakage after left lateral neck dissection in patients with thyroid cancer., Methods: A total of 491 patients with thyroid cancer underwent left lateral neck dissection with identification of the thoracic duct following ice cream consumption. Before closing the wound, the anesthesiologist increased the intrathoracic pressure to observe chyle leakage. If chyle leakage occurred postoperatively, the drain was removed using the drain negative pressure release test., Results: Postoperative chyle leakage was observed in 18 of the 491 patients who underwent left lateral neck dissection. We treated 17 patients conservatively and 1 patient surgically. Drains were removed within five days in all patients. After the drain negative pressure release test had been performed in eight patients, the drainage volume significantly decreased from an average of 175 ml to 31 ml per day. The average number of days until the removal of the drainage tube was 3.2 days. No perioperative complications were associated with ice cream consumption., Conclusions: In left lateral neck dissection for thyroid cancer, performing surgery following ice cream consumption does not completely prevent chyle leakage; however, early drain removal is possible because there is only mild leakage., (© 2023. The Author(s).)

Introduction: Older patients with cancer are less likely to express their treatment preferences than younger patients. Question prompt lists (QPLs) facilitate communication between patients and physicians. Geriatric assessment (GA) is recommended when older patients with cancer make treatment decisions. This study estimated the effect size of a shared decision-making (SDM) support program combining QPLs with GA in terms of patients' subjective evaluation of the SDM process for a future definitive randomized controlled trial. We also evaluated the number and quality of aging-related communication during consultations, and feasibility and acceptability of the study for exploratory purposes., Materials and Methods: This is a pilot study with randomized allocation and blind evaluation. Patients aged 65 years or older at the National Cancer Center Hospital, Tokyo, Japan, scheduled to discuss the changes of their treatment, were randomly assigned in a 1:1 ratio to the SDM support program or usual care. This program consisted of 30-60 min of face-to-face coaching, with QPLs and GA provided before the coaching. As the primary endpoint, the decisional conflict scores given by the patients immediately after the consultation were compared between the two groups. For the secondary endpoints, the number and quality of aging-related communications during the consultations were assessed by evaluators (blinded) using audio-recordings. Adherence, burden, and usefulness were assessed for evaluating feasibility and acceptability of the SDM support program., Results: Forty patients were enrolled. All patients completed the GA questionnaire, for which 70% did not require any individual assistance. Answering the questionnaires took approximately 11 min. The decisional conflict scores were mean [standard deviation (SD)]: 19.3 [10.8] vs. 18.0 [11.1] (effect size: Cohen's d = 0.12) for the SDM support program and usual care groups, respectively. The number of aging-related communications during the consultation for the new treatment was higher in the SDM support program group than the usual care (mean [SD]: 3.3 [1.2] vs. 2.2 [1.5], effect size: cohen's d = 1.32). Patients felt that the SDM support program was useful but not burdensome or difficult., Discussion: The SDM support program was considered useful and feasible for older patients and able to facilitate communication regarding aging-related concerns., Trial Registration Number: The study protocol was registered on September 23, 2020, in the UMIN Clinical Trials Registry (UMIN000041867)., Competing Interests: Declaration of Competing Interest N. Boku received honorarium from Ono, Bristol Myers Squibb, Eli Lilly, Daiichi Sankyo, Taiho. Other authors declare that they have no known competing financial interests or personal relationships that could have influenced the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Salmonella enterica serovar Gallinarum ( S. gallinarum ) is an important host-specific pathogen that causes fowl typhoid, a severe systemic, septicemic, and fatal infection, in chickens. S. gallinarum causes high morbidity and mortality in chickens and poses a significant burden and economic losses to the poultry industry in many developing countries. However, the virulence factors and mechanisms of S. gallinarum -induced systemic infection in chickens remain poorly understood. In this study, we constructed a Salmonella pathogenicity island-14 (SPI-14) mutant strain (mSPI-14) of S. gallinarum and evaluated the pathogenicity of mSPI-14 in the chicken systemic infection model. The mSPI-14 exhibited the same level of bacterial growth and morphological characteristics but significantly reduced resistance to bile acids compared with the wild-type (WT) strain in vitro . The virulence of mSPI-14 was significantly attenuated in the chicken oral infection model in vivo . Chickens infected with WT showed typical clinical symptoms of fowl typhoid, with all birds succumbing to the infection within 6 to 9 days post-inoculation, and substantial increases in bacterial counts and significant pathological changes in the liver and spleen were observed. In contrast, all mSPI-14-infected chickens survived, the bacterial counts in the organs were significantly lower, and no significant pathological changes were observed in the liver and spleen. The expression of interleukin (IL)-1β, IL-12, CXCLi1, tumor necrosis factor (TNF)-α, and interferon (IFN)-γ in the liver of mSPI-14-infected chickens were significantly lower than those in the WT-infected chickens. These results indicate that SPI-14 is a crucial virulence factor in systemic infection of chickens, and avirulent mSPI-14 could be used to develop a new attenuated live vaccine to prevent S. gallinarum infection in chickens., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Hu, Ojima, Zhu, Yu, Sugiyama, Haneda, Okamura, Ono and Hu.)

The World Health Organization Regional Office for Africa (WHO/AFRO) faces members who encounter annual disease epidemics and natural disasters that necessitate immediate deployment and a trained health workforce to respond. The gaps in this regard, further exposed by the COVID-19 pandemic, led to conceptualizing the Strengthening and Utilizing Response Group for Emergencies (SURGE) flagship in 2021. This study aimed to present the experience of the WHO/AFRO in the stepwise roll-out process and the outcome, as well as to elucidate the lessons learned across the pilot countries throughout the first year of implementation. The details of the roll-out process and outcome were obtained through information and data extraction from planning and operational documents, while further anonymized feedback on various thematic areas was received from stakeholders through key informant interviews with 60 core actors using open-ended questionnaires. In total, 15 out of the 47 countries in WHO/AFRO are currently implementing the initiative, with a total of 1,278 trained and validated African Volunteers Health Corps-Strengthening and Utilizing Response Groups for Emergencies (AVoHC-SURGE) members in the first year. The Democratic Republic of Congo (DRC) has the highest number (214) of trained AVoHC-SURGE members. The high level of advocacy, the multi-sectoral-disciplinary approach in the selection process, the adoption of the one-health approach, and the uniqueness of the training methodology are among the best practices applauded by the respondents. At the same time, financial constraints were the most reported challenge, with ongoing strategies to resolve them as required. Six countries, namely Botswana, Mauritania, Niger, Rwanda, Tanzania, and Togo, have started benefiting from their trained AVoHC-SURGE members locally, while responders from Botswana and Rwanda were deployed internationally to curtail the recent outbreaks of cholera in Malawi and Kenya., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Conteh, Braka, Assefa, Daniel, Ngofa, Okeibunor, Omony, Hakizimana, Wondimagegnehu, Djingarey, Kobie, Kirigia, Mbasha, Fekadu, Aderinola, Ahmat, Asamani, Pallawo, Mpia, Diaw, Kourouma, Davi, Condé, Moakofhi, Balami, Okamura, De Wee, Joseph, Saguti, Andemichael, Abok, Avwerhota, Livinus, Okoronwanja, Makayoto, Rutagengwa, Ba, Kandako, Livinus, Diallo, Tengomo, Belizaire, Daizo, Muzi, Yam, Ramadan, D'khil, Bonkoungou, O'malley and Gueye.)

Objective: To describe patients' perceptions of the patient-centeredness of their communication with healthcare providers in Japan, and to examine factors associated with these perceptions., Methods: We analyzed the cross-sectional data from the INFORM Study 2020, which is a nationwide survey on health information access in Japan. A total of 3605 respondents completed the survey. Our primary outcome was the nine elements of the patient-centered communication scale (PCCS), which was compiled from 2703 respondents (75.0%) reporting at least one provider visit within 12 months. It was rated on a four-point Likert scale: always, usually, sometimes, and never. We used binary logistic regression to examine the association between sociodemographic and health-related variables, and each element of the PCCS., Results: For all elements, the percentage of respondents who agreed that their healthcare providers always communicated in a patient-centered way was low (17-31%). Patients with higher age, higher education, poorer general health status and a larger number of visits to providers in the previous 12 months were more likely to have positive perception., Conclusion: Patient-centered communication as reported in a national sample in Japan was low., Clinical Implications: Efforts are needed to improve the patient-centeredness of patient-provider communication in Japan to optimize health outcomes., 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 The Authors. Published by Elsevier B.V. All rights reserved.)

Objectives: Physical exercise is known to induce expression of the neuroprotective brain derived neurotrophic factor (BDNF) in the hippocampus. This study examined the effects of physical exercise on hippocampal BDNF expression and the potential benefits for preventing remote secondary hippocampal damage and neurological impairment following intracerebral hemorrhage (ICH)., Materials and Methods: Wistar rats were randomly assigned to sham-operated, ICH, and ICH followed by exercise (ICH/Ex) groups. The two ICH groups were injected with type IV collagenase into the left basal ganglia, while sham animals were injected with equal-volume saline. The ICH/Ex group rats ran on a treadmill at 11 m/min for 30 min/day from day 3 to 16 post-ICH. All animals were examined for neurological function on day 2 pretreatment and from day 3 to 15 posttreatment, for spontaneous motor activity in the open field on day 15, and for cognitive ability using the object location test on day 16. Animals were then euthanized and bilateral hippocampi collected for gene expression analyses., Results: Experimental ICH induced neurological deficits that were not reversed by exercise. In contrast, ICH did not alter spontaneous activity or object location ability. Expression of BDNF mRNA of the ICH group was significantly downregulated in the ipsilateral hippocampus compared to the SHAM group, but this downregulation was not shown in the ICH/Ex group. The ICH/Ex group showed the downregulation of caspase-3 mRNA expression in the contralateral hippocampus compared to the SHAM group, while neither ICH nor exercise influenced toll-like receptor 4 mRNA expression., Conclusions: ICH induced the secondary BDNF downregulation in the hippocampus remote from the lesion, whereas physical exercise might partially mitigate the downregulation., 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.)

Background & Aims: Nutritional status is a significant issue in an aging society; however, the impact of the nutritional status of older individuals using long-term care services on the caregiving burden remains unclear. This systematic review and meta-analysis aimed to investigate the impact of nutritional issues on adverse outcomes in older individuals using long-term care services., Methods: We used data from the Cochrane Central Register of Controlled Trials, MEDLINE, Embase, Web of Science, CINAHL, and Ichu-shi Web databases. Original articles published in English or Japanese between January 2000 and July 2022 were included. The inclusion criteria were interventional and observational studies on individuals using long-term care services with aged ≥65 years and a focus on body weight or weight loss. Data on adverse outcomes related to caregiving burden, including the number of people requiring care, mortality, complications, activities of daily living (ADL), and quality of life, were collected., Results: The literature search yielded 7873 studies, of which 35 were ultimately included. Seven observational studies investigated mortality outcomes, and seven examined ADL outcomes. The meta-analysis revealed significantly higher mortality rates in individuals classified as underweight (BMI <18.5 kg/m 2 ) than in those with BMI ≥18.5 kg/m 2 (risk ratio [RR] 1.49; 95 % confidence interval [CI] 1.31 to 1.73, 0.22; I 2 93 %). Further, on categorising the participants based on a BMI cutoff of 25 kg/m 2 , those with a BMI of <25 kg/m 2 had a significantly increased mortality rate (RR 1.21; 95 % CI 1.04-1.40; I 2  = 98 %). BMI and weight loss did not affect ADL., Conclusions: Our findings indicate that underweight and weight loss are significantly associated with increased mortality in older individuals using long-term care services. Therefore, appropriate weight management is recommended for this population. However, further research is necessary owing to the high heterogeneity observed in this study., Competing Interests: Declaration of competing interest We have no conflicts of interest to declare., (Copyright © 2023 European Society for Clinical Nutrition and Metabolism. Published by Elsevier Ltd. All rights reserved.)

Early mobilization of hospitalized patients is beneficial under certain circumstances. This has been applied in clinical practice for patients with acute heart failure (HF). However, its current definition, effectiveness, and safety are not well established. This review aimed to clarify the current definition of "early mobilization," and summarize its effectiveness and safety in acute HF. We conducted a scoping review to define early mobilization (Part 1) and a systematic review and meta-analysis (Part 2) to evaluate its effectiveness and safety. For Part 1, we searched MEDLINE (Ovid), and for Part 2, we searched the Cochrane Central Register of Controlled Trials, MEDLINE (Ovid), Embase (ProQuest Dialog), CINAHL, and PEDro. We included 12 studies in Part 1 and defined early mobilization as protocol-based interventions or walking within 3 days of admission. Based on this definition, two observational studies were included in Part 2, with no randomized controlled trials. Early mobilization may result in a large reduction in the readmission rate compared with that of the control (two studies, 283 participants: odds ratio 0.25, 95 % confidence interval 0.14 to 0.42; I 2  = 0 %; low certainty evidence). We could not define frequency, intensity, or quantity because many of the included studies did not describe them. In conclusions, our review suggests that early mobilization, defined as protocol-based interventions or walking within 3 days of admission, may be associated with a low readmission rate in patients with acute HF. Future studies are essential, to investigate the causal relationship between early mobilization and possible outcomes., Competing Interests: Declaration of competing interest The authors declare that there is no conflict of interest., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Epigenetic regulation is involved in post-stroke neuroplasticity. We investigated the effects of intracerebral hemorrhage (ICH) on histone acetylation and gene expression related to neuronal plasticity in the bilateral sensorimotor cortices, which may affect post-stroke sensorimotor function. Wistar rats were randomly divided into the SHAM and ICH groups. We performed ICH surgery stereotaxically based on the microinjection of a collagenase solution in the ICH group. Foot fault and cylinder tests were performed to evaluate motor functions at 4-time points, including pre-ICH surgery. The amount of acetyl histones and the mRNA expression of neurotrophic factors crucial to neuroplasticity in the bilateral sensorimotor cortices were analyzed approximately 2 weeks after ICH surgery. Sensorimotor functions of the ICH group were inferior to those of the SHAM group during 2 weeks post-ICH. ICH increased the acetylation of histone H3 and H4 over the sham level in the ipsilateral and contralateral cortices. ICH increased the mRNA expression of IGF-1, but decreased the expression of BDNF compared with the sham level in the ipsilateral cortex. The present study suggests that histone acetylation levels are enhanced in bilateral sensorimotor cortices after ICH, presenting an altered epigenetic platform for gene expressions related to neuronal plasticity.