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Introduction: the occurrence of breast cancer in men is an indication for genetic counseling and must be systematically sought. The objective of this work was to describe the histopathological and molecular aspects of human breast cancer. Material and Methods: This was a cross-sectional study with retrospective collection from January 2007 to September 2021, including all cases of male breast cancer diagnosed by histology with immunohistochemical examination. The variables studied were histopathological and molecular. The samples were fixed in 10% formalin and processed using the standard hematoxylin-eosin and immunohistochemistry technique. Results: A total of 8 cases of male breast cancer were collected. Each case underwent histological and immunohistochemical examination. Age ranged from 8 to 77 years with a mean age of 50.63±20.79. Consultation time of less than 12 months was common with the presence of a breast nodule as the reason. The left breast was as affected as the right breast. Tumor size T3 (5 cm and more) predominated with 3 cases. The nature of the sample received was: 04 biopsies and 04 lumpectomies. Infiltrative carcinoma of non-specific type was common: 7 cases (or 87.5%) with Elston and Ellis grade II in 75% of cases. Luminal A and triple negative were predominant with 3 cases each (37.5%). Conclusion: Breast cancer is increasingly diagnosed in men at all ages. [ABSTRACT FROM AUTHOR]

Abstract Randomized controlled trials are considered the “gold standard” for evaluating the effectiveness of an intervention. However, large-scale, cluster-randomized trials are complex and costly to implement. The generation of accurate, reliable, and high-quality data is essential to ensure the validity and generalizability of findings. Robust quality assurance and quality control procedures are important to optimize and validate the quality, accuracy, and reliability of trial data. To date, few studies have reported on study procedures to assess and optimize data integrity during the implementation of large cluster-randomized trials. The dearth of literature on these methods of trial implementation may contribute to questions about the quality of data collected in clinical trials. Trial protocols should consider the inclusion of quality assurance indicators and targets for implementation. Publishing quality assurance and control measures implemented in clinical trials should increase public trust in the findings from such studies. In this manuscript, we describe the development and implementation of internal and external quality assurance and control procedures and metrics in the Pneumococcal Vaccine Schedules trial currently ongoing in rural Gambia. This manuscript focuses on procedures and metrics to optimize trial implementation and validate clinical, laboratory, and field data. We used a mixture of procedure repetition, supervisory visits, checklists, data cleaning and verification methods and used the metrics to drive process improvement in all domains.

ABSTRACT Background Cancer cachexia complicates advanced non‐small cell lung cancer (NSCLC); however, it remains unclear how often cachexia occurs and how it affects the course of chemotherapy in patients receiving first‐line systemic therapy. Methods We conducted a multicentre, prospective observational study and enrolled previously untreated NSCLC patients with Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0–2 and cachexia between September 2020 and September 2021. The primary outcome measure was the trends in the Functional Assessment of Anorexia/Cachexia Treatment and Anorexia/Cachexia Subscale [FAACT (A/CS)] scores by cohort. Secondary outcome measures included the incidence of cachexia before the initiation of first‐line systemic therapy, quality of life (QOL) measures, body weight (BW) changes, and efficacy and safety of first‐line systemic therapy. Results A total of 887 consecutive patients with previously untreated advanced NSCLC and ECOG PS of 0–2 who were initiated on first‐line systemic therapy were evaluated. A total of 281 patients (31.7%) experienced BW loss consistent with the criteria of cachexia, and 186 were evaluated for QOL, BW and outcome measurements. Overall, 180/186 patients received first‐line systemic therapy. Cohort 1 (targeted therapy), cohort 2 [cytotoxic chemotherapy (CTx) ± immune checkpoint inhibitors (ICIs)] and cohort 3 (ICIs) included 42, 98 and 40 patients, respectively. There were significant variations in QOL trends by cohort, with chemotherapy‐associated emesis affecting early appetite‐related QOL. The change in the FAACT (A/CS) score at 1 week from baseline was worse in cohort 2 (the least square mean change ± standard error: −3.0 ± 0.9) than in cohorts 1 (1.6 ± 1.2, p = 0.003) and 3 (1.8 ± 1.0, p = 0.002); meanwhile, the change at 6 weeks was worse in cohort 1 (−1.5 ± 1.2) than in cohorts 2 (3.6 ± 0.9, p = 0.001) and 3 (3.5 ± 1.1, p = 0.004). BW reduction was observed in all cohorts within 6 weeks of therapy initiation. The targeted therapy cohort demonstrated superior progression‐free survival (PFS) and overall survival (OS) to CTx ± ICIs cohort or ICIs cohort (median PFS was 9.7 months, 6.3 months, 3.1 months, in cohort 1, 2, 3, respectively (cohort 1 vs. cohort 2: HR, 0.58, p = 0.018; cohort 1 vs. cohort 3: HR, 0.41, p = 0.001); median OS was not reached, 15.8 months, 9.9 months, respectively (cohort 1 vs. cohort 2: HR, 0.52, p = 0.033; cohort 1 vs. cohort 3: HR, 0.37, p = 0.003). Conclusions Approximately 1/3 patients with previously untreated advanced NSCLC have cachexia. Appetite‐related QOL trends vary based on the type of first‐line systemic therapy in cachectic NSCLC patients, and the PFS and OS of these patients seemed to be shorter.

Migratory birds carry ticks harboring various pathogens, including the zoonotic Yezo virus. In Hokkaido, Japan, we collected ticks from migratory birds during 2020–2021. Eight of 385 pools, comprising 2,534 ticks, tested positive for Yezo virus RNA, suggesting Yezo virus might be spread through the flyways of migratory birds.

Abstract Background In the context of cardiovascular surgery, the foremost concern lies in delayed functional recovery, as typified by the acquisition of independent walking after surgery, among older patients with decline in skeletal muscle mass and quality. Computed tomography (CT), which is typically employed for the preoperative assessment of pathological conditions in patients undergoing cardiovascular surgery, is also suitable for screening for potential decline in skeletal muscle mass and quality. The aim of this study was to examine the predictive capabilities of CT‐derived parameters such as muscle mass and muscle quality for the delayed acquisition of independent walking in the postoperative period. Methods This retrospective study enrolled consecutive Japanese patients who underwent elective cardiovascular surgery between May 2020 and January 2023. In total, 139 patients were included in the analyses. Based on the preoperative CT image, the psoas muscle volume index (PMVI) and psoas muscle attenuation (PMA) were calculated. Information on patient characteristics, including preoperative physical fitness such as handgrip strength/body mass index (GS/BMI), short physical performance battery (SPPB), and 6‐min walking distance (6MWD), were obtained from the medical records. We defined delayed acquisition of independent walking after surgery as the inability to walk 100 m within 4 days after surgery. Results The median age of the patients was 72 (interquartile: 64–78) years, and 74.8% (104/139) were men; 47.5% corresponded to the delayed group. The areas under the curves of SPPB, GS/BMI, 6MWD, PMVI, and PMA against delayed acquisition of independent walking after surgery were 0.68 [95% confidence interval (CI): 0.59 to 0.77], 0.72 (95% CI: 0.63 to 0.80), 0.73 (95% CI: 0.65 to 0.82), 0.69 (95% CI: 0.60 to 0.78), and 0.78 (95% CI: 0.70 to 0.85), respectively. In the multivariate logistic regression analysis, low PMA was significantly associated with delayed acquisition of independent walking even after adjustment for patient characteristics including physical fitness [model 1: SPPB (OR, 1.14; 95% CI: 1.03–1.25), model 2: GS/BMI (OR, 1.13; 95% CI: 1.03–1.25), and model 3: 6MWD (OR, 1.14; 95% CI: 1.03–1.25)], but PMVI was not. Conclusions Our study revealed a strong association between PMA, a marker of CT‐derived muscle quality, and the postoperative delay in achieving independent walking in patients who underwent cardiovascular surgery. The technique to obtain information on muscle quality during the time period before surgery may be an option for timely therapeutic intervention in patients who may have delayed acquisition of independent walking after surgery.

Abstract Background Rotavirus B (RVB) causes diarrhea in humans and pigs. Although various RVB strains were identified in humans and various animals globally, little is known about the epidemiology RVB infection in Africa. In this study, we attempted to examine the prevalence of RVB infection in pig populations in Zambia. Methods Metagenomic analyses were conducted on pig feces collected in Zambia to detect double stranded RNA viruses, including RVB. To clarify the prevalence of RVB infection in pig populations in Zambia, 147 fecal samples were screened for the RVB detection by RT-qPCR. Full genome sequence of a detected RVB was determined by Sanger sequencing and genetically analyzed. Results The metagenomic analyses revealed that RVB sequence reads and contigs of RVB were detected from one fecal sample collected from pigs in Zambia. RT-qPCR screening detected RVB genomes in 36.7% (54/147) of fecal samples. Among 54 positive samples, 13 were positive in non-diarrheal samples (n = 48, 27.1%) and 41 in diarrheal samples (n = 99, 41.4%). Genetic analyses demonstrated that all the segments of ZP18-18, except for VP4, had high nucleotide sequence identities (80.6–92.6%) with all other known RVB strains detected in pigs. In contrast, the VP4 sequence of ZP18-18 was highly divergent from other RVB strains (

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

Abstract Modification of guanosine to N7-methylguanosine (m7G) in the variable loop region of tRNA is catalyzed by the METTL1/WDR4 heterodimer and stabilizes target tRNA. Here, we reveal essential functions of Mettl1 in Drosophila fertility. Knockout of Mettl1 (Mettl1-KO) causes no major effect on the development of non-gonadal tissues, but abolishes the production of elongated spermatids and mature sperm, which is fully rescued by expression of a Mettl1-transgene, but not a catalytic-dead Mettl1 transgene. This demonstrates that Mettl1-dependent m7G is required for spermatogenesis. Mettl1-KO results in a loss of m7G modification on a subset of tRNAs and decreased tRNA abundance. Ribosome profiling shows that Mettl1-KO led to ribosomes stalling at codons decoded by tRNAs that were reduced in abundance. Mettl1-KO also significantly reduces the translation efficiency of genes involved in elongated spermatid formation and sperm stability. Germ cell-specific expression of Mettl1 rescues disrupted m7G tRNA modification and tRNA abundance in Mettl1-KO testes but not in non-gonadal tissues. Ribosome stalling is much less detectable in non-gonadal tissues than in Mettl1-KO testes. These findings reveal a developmental role for m7G tRNA modification and indicate that m7G modification-dependent tRNA abundance differs among tissues.

Oral health and general health are closely linked and dependent in humans. The total disappearance of teeth leads to the loss of proprioceptive control systems, the modification of the entire tissue system and therefore great psychological fragility. Pre-prosthetic surgery consists of restoring the osteo-mucosal tissues to allow the installation of a prosthesis. The objective: was to assess the need for pre-surgical prosthetic preparation for the totally edentulous at the CHU-CNOS of Bamako. Method and materials: This was a prospective, descriptive study extending over a period of 8 months (from January 1 to August 31, 2021). Patients seen at the removable prosthesis service for a consultation in whom a diagnosis of edentulism was made constituted the study population. We carried out an exhaustive recruitment of totally edentulous people received at the service for the completed removable prosthesis who agreed to participate in the study. The data were collected using an individual survey form and analyzed with SPSS version 20.0 software. Result: A total of 50 patients were registered, including 14 men or 28% and 36 women or 72%. The sex ratio was 0.38 in favor of women. The 60 to 69 age group was the most represented with 19% and the average age was 56 years. The demand for prosthetic restoration for aesthetic and functional purposes represented the reasons for consultation in 46%, 44% of cases and pain in 10% of cases the most expressed concern by patients. Oral hygiene was average 64%, good at 20% and poor at 16%. Tooth extraction represented 70% of cases, without surgery 20% of cases and osteotomy 10% of cases as pre-surgical prosthetic treatment. The ridge was poorly resorbed at 40%, moderately resorbed at 30%, very resorbed at 20% and the ridge was negative at 10%, 50% of patients did not wear a prosthesis, 34% of patients wore partial removable prostheses and 16% wore removable total prostheses. Among our patients 66% had normal frenulums, 22% had short frenulums and 12% had wide frenulums. Conclusion: This study made it possible to highlight the real needs in pre-surgical prosthetic preparation. Among these needs, multiple tooth extraction remains the most common pre-prosthetic surgical procedure.

The management of the aesthetic parameter represents an important factor in the integration of removable prostheses. The current major social interest in beauty has made patients more and more demanding with regard to their appearance. [1] The main objective of this study was to assess the aesthetic expectations of patients with removable prostheses at the CHU-CNOS in Bamako. Our prospective and descriptive study having collected 78 patients was carried out over a period from March 2, 2019 to March 9, 2020 at the removable prosthesis department of the CHU-CNOS in Bamako. The female sex represented 55.1% with a sex ratio of 0.65. Removable prosthetic rehabilitation mainly concerned young adults aged 21-41 (41%) Aesthetics was the main reason for rehabilitation most represented with 60.3% of cases. The white tooth was the most requested dental shade with 70.5% of cases Bonded teeth were the most represented in our patients with 71.79% of cases. Pink gum was the shade most requested by our patients with 43.6% of cases. Obtaining a personalized prosthesis in harmony with the facial framework, giving the illusion of naturalness and restoring the smile to patients is the objective to be achieved.

ABSTRACT The effects of sodium‐glucose cotransporter 2 (SGLT2) inhibitors on mesenchymal‐epithelial transition factor (MET) inhibitor‐induced edema remain unclear. In a patient with tepotinib‐induced edema and an N‐terminal pro‐brain natriuretic peptide (NTproBNP) level ≥ 300 pg/mL, the addition of empagliflozin to loop diuretics reduced the edema. This suggests that empagliflozin may be a treatment option for MET inhibitor‐induced edema.

ABSTRACT Grimontia hollisae, an uncommon cause of sepsis, was identified in a 9‐month‐old infant in Africa without confirmed seafood consumption. Prompt diagnosis through blood culture and targeted antibiotic therapy ensured recovery, emphasizing the need for increased awareness, enhanced diagnostic tools, and active monitoring of emerging pathogens in tropical and resource‐limited regions. We present a case report involving a 9‐month‐old infant who exhibited symptoms of acute gastroenteritis. The blood culture revealed G. hollisae . We treated the infant on empirical first‐line antibiotics of IV ceftriaxone, IV gentamicin, zinc tablets, and syrup paracetamol for 5 days after which the child was discharged on oral metronidazole following resolution of symptoms. This case highlights the importance of G. hollisae in causing sepsis in infants in tropical settings. It also emphasizes the need for blood culture investigation and administering the appropriate antibiotics in the diagnosis of children presenting with suspected sepsis.

In an increasingly digitalised and interconnected world, assessing the strength of interpersonal ties in social networks is crucial for fields such as business, marketing and sociology. Traditional methods for evaluating Tie Strength (TS), which often classify relationships as either ”strong” or ”weak”, fail to capture the uncertainty and ambiguity of human interactions. This study proposes a Fuzzy-based System for Assessment of Tie Strength (FSATS). We develop and evaluate two models: FSATSM1, which utilises three input parameters Interaction Time (IT), Level of Intimacy (LoI) and Emotional Intensity (EI); and FSATSM2, where we introduce Reciprocity (Rc) as an additional parameter. Through simulations, we compare the performance of both models for the assessment of TS. The simulation results show that for FSATSM1, when IT is 0.9 and EI is 0.7 for all values of LoI, the TS values are more than 0.5. While, for FSATSM2, when IT is 0.9, for EI 0.1 (Rc more than 0.8), EI 0.5 (Rc more than 0.5) and EI 0.9 (Rc more than 0.2), all values of TS are more than 0.5, indicating a strong relationship. The results suggest that FSATSM2 provides a more accurate reflection of real-world relationships, which can be applied in contexts such as Social Customer Relationship Management (SCRM), enabling businesses to enhance customer engagement strategies.

Summary: Background: Emergence of SARS-CoV-2 variants that escape neutralising antibodies hampers the development of vaccines and therapeutic antibodies against SARS-CoV-2. IGHV3-53/3-66-derived public antibodies, which are generally specific to the prototype virus and are frequently induced in infected or vaccinated individuals, show minimal affinity maturation and high potency against prototype SARS-CoV-2. Methods: Monoclonal antibodies isolated from a Delta breakthrough infection case were analysed for cross-neutralising activities against SARS-CoV-2 variants. The broadly neutralising antibody K4-66 was further analysed in a hamster model, and the effect of somatic hypermutations was assessed using the inferred germline precursor. Findings: Antibodies derived from IGHV3-53/3-66 showed broader neutralising activity than antibodies derived from IGHV1-69 and other IGHV genes. IGHV3-53/3-66 antibodies neutralised the Delta variant better than the IGHV1-69 antibodies, suggesting that the IGHV3-53/3-66 antibodies were further maturated by Delta breakthrough infection. One IGHV3-53/3-66 antibody, K4-66, neutralised all Omicron subvariants tested, including EG.5.1, BA.2.86, and JN.1, and decreased the viral load in the lungs of hamsters infected with Omicron subvariant XBB.1.5. The importance of somatic hypermutations was demonstrated by the loss of neutralising activity of the inferred germline precursor of K4-66 against Beta and Omicron variants. Interpretation: Broadly neutralising IGHV3-53/3-66 antibodies have potential as a target for the development of effective vaccines and therapeutic antibodies against newly emerging SARS-CoV-2 variants. Funding: This work was supported by grants from AMED (JP23ym0126048, JP22ym0126048, JP21ym0126048, JP23wm0125002, JP233fa627001, JP223fa627009, JP24jf0126002, and JP22fk0108572), and the JSPS (JP21H02970, JK23K20041, and JPJSCCA20240006).

Background: The establishment of a formal diagnosis of post-traumatic stress disorder (PTSD) for children and adolescents is the foundation for advancing pertinent clinical research and formulating proper treatment and management. However, a validated diagnostic tool for PTSD in children and adolescents is lacking in Japan.Objective: To examine the cross-cultural validity and reliability of the Japanese Clinician-Administered PTSD Scale for the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5), child and adolescent version (CAPS-CA-5-J).Method: Overall, 73 children who had experienced potentially traumatic events were recruited from three medical facilities. The linguistically validated CAPS-CA-5-J was conducted by trained psychiatrists and psychologists. Additionally, children and their caretakers completed questionnaires such as the UCLA PTSD reaction index for DSM-5 (PTSD-RI-5), Depression Self-Rating Scale for Children (DSRDC), and Strength and Difficulties Questionnaire (SDQ); 16 participants were randomly selected for the inter-rater reliability assessment.Results: Owing to missing values in the CAPS-CA-5-J and PTSD-RI-5, 68 children were included in the final analysis. Regarding reliability, the CAPS-CA-5-J showed excellent internal consistency (Cronbach’s alpha coefficient = 0.90) and interrater agreement (kappa coefficient = 0.88). Convergent validity was supported by a strong correlation between the total severity scale of the CAPS-CA-5-J and the PTSD-RI-5 scores (Pearson’s correlation coefficient = 0.82). Divergent validity was indicated by a moderate correlation between the CAPS-CA-5-J and DSRDC, and no correlation was found with the SDQ scores.Conclusions: This study is the first to validate a structured clinical interview for children and adolescents with PTSD in Japan. The psychometric properties of the CAPS-CA-5-J were good enough and comparable to those reported in previous validation studies. Therefore, the CAPS-CA-5-J can be considered reliable and valid for use in Japan.

Background: The survival benefit of adjuvant chemotherapy after surgical resection of oligometastases from colorectal cancer (CRC) remains unclear. The prognostic role of circulating-tumor DNA (ctDNA) was reported recently and a risk stratification strategy based on monitoring minimal/molecular residual disease (MRD) has been proposed, however, which drug regimen is most effective for ctDNA-positive patients is unknown. Methods/Design: Oligometastatic CRC patients planning to undergo surgery were registered in this study. After metastasectomy, the registered patients were enrolled in the treatment arm, in which 8 courses of modified-FOLFOXIRI (mFOLFOXIRI; irinotecan 150 mg/m2, oxaliplatin 85 mg/m2, l-leucovorin (l-LV) 200 mg/m2, and 46-h continuous infusion of 5-fluorouracil (5-FU) 2400 mg/m2 every 2 weeks) followed by 4 courses of 5-FU/l-LV are administered. The patients who did not meet the eligibility criteria for the treatment arm or did not consent to mFOLFOXIRI enrolled in the observation arm in which standard of care treatment is provided. Prospective blood collections for retrospective ctDNA analysis are scheduled pre-surgery, and at 28 days, 4 and 7 months after surgery. The primary endpoint is treatment compliance at 8 courses of mFOLFOXIRI and the key secondary endpoints are the ctDNA-positivity rate and survival outcomes in ctDNA-positive and -negative groups. A total of 85 patients will be enrolled from 11 institutions. First patient-in was on July 2020. Accrual completed in February 2024. Discussion: This study will potentially identify a better treatment strategy for patients with resectable oligometastatic CRC having postsurgical ctDNA positivity, compared to the current standard of care approaches.

Yezo virus (YEZV) is an emerging tick-borne virus that causes acute febrile illness. It has been continuously reported in patients and ticks in Japan and China since its first identification in Hokkaido, Japan. While serological tests have demonstrated that YEZV infections are prevalent in wild animals, such as raccoons (Procyon lotor), the determinants of infection in wild animals remain largely unknown. We examined the prevalence of YEZV in invasive raccoons, native tanukis (raccoon dogs, Nyctereutes procyonoides albus), and ticks in six study areas in Hokkaido between 2018 and 2023 to identify ecological factors underlying YEZV infection in wild animals. YEZV RNA fragments were detected in 0.22% of the 1,857 questing ticks. Anti-YEZV antibodies were detected in 32 of the 514 (6.2%) raccoon serum samples and in 5 of the 40 (12.5%) tanuki serum samples. Notably, the seroprevalence in raccoons varied significantly in one of the study areas over the years, that is, 0.0%, 60.0%, and 28.6% in 2021, 2022, and 2023, respectively, implying the temporary emergence of YEZV microfoci. By analyzing the tick load and YEZV seropositivity in raccoons in a field-based setting, we found a positive correlation between adult Ixodes ovatus load and YEZV-antibody positivity, highlighting the importance of I. ovatus in YEZV infection in wild animals. We also explored the environmental and host factors influencing YEZV seropositivity in raccoons and tanukis and found that landscape factors, such as the size of forest area around the trap site, were crucial for YEZV seropositivity in these animals. The significant variables for YEZV seropositivity in raccoons were partially different from those affecting tick infestation intensity in raccoons. The present results extend our understanding of tick-borne virus circulation in the field, emphasizing the unique ecology of the emerging YEZV.

Beiji nairovirus (BJNV), in the family Nairoviridae, the order Bunyavirales, was recently reported as a causative agent of an emerging tick-borne zoonotic infection in China. This study investigated the prevalence of BJNV in ticks in Japan. Screening of over 2,000 ticks from multiple regions revealed a widespread distribution of BJNV and BJNV-related viruses in Japan, particularly in the northern island, and in other high altitude areas with exclusive occurrence of Ixodes ticks. Phylogenetic analysis identified three distinct groups of nairoviruses in ticks in Japan: BJNV, Yichun nairovirus (YCNV) and a newly identified Mikuni nairovirus (MKNV). BJNV and YCNV variants identified in ticks in Japan exhibited high nucleotide sequence identities to those in China and Russia with evidence of non-monophyletic evolution among BJNVs, suggesting multiple cross-border transmission events of BJNV between the Eurasian continent and Japan. Whole genome sequencing of BJNV and MKNV revealed a unique GA-rich region in the S segment, the significance of which remains to be determined. In conclusion, the present study has shown a wide distribution and diversity of BJNV-related nairoviruses in Ixodes ticks in Japan and has identified unique genomic structures. The findings demonstrate the significance of BJNV as well as related viruses in Japan and highlight the necessity of monitoring emerging nairovirus infections and their potential risks to public health.

Revealing interactions between ticks and wild animals is vital for gaining insights into the dynamics of tick-borne pathogens in the natural environment. We aimed to elucidate the factors that determine tick infestation in wild animals by investigating ticks on invasive raccoons (Procyon lotor) in Hokkaido, Japan. We first examined the composition, intensity, and seasonal variation of ticks infesting raccoons in six study areas in Hokkaido from March 2022 to August 2023. In one study area, ticks infesting tanukis (raccoon dog, Nyctereutes procyonoides albus) were collected in May to July in both 2022 and 2023, and questing ticks were collected from the vegetation by flagging every other week in the same period. Next, we screened 17 environmental and host variables to determine factors that affect the number of ticks infesting raccoons using generalized linear (mixed) models. From 245 raccoons, we identified a total of 3,917 ticks belonging to eight species of two genera: the most prominent species were Ixodes ovatus (52.9 %), followed by Haemaphysalis megaspinosa (14.4 %), Ixodes tanuki (10.6 %), and Ixodes persulcatus (9.5 %). Ixodes ovatus was also predominant among questing ticks and ticks infesting tanukis. Although I. tanuki was frequently collected from raccoons and tanukis, it was rarely collected in the field. The variables that significantly affected the infestation on raccoons differed by genus, species and developmental stage of the tick. For instance, the infestation of adult I. ovatus was significantly affected by four variables: night-time temperature during nine days before capturing the raccoon, the size of forest area around the capture site, sex of the raccoon, and sampling season. The first two variables were also responsible for the infestation on raccoons of almost all species and stages of ticks. Our study revealed that the number and composition of ticks infesting raccoons can be affected not only by landscape of their habitats but also by weather conditions in several days before capturing.

Introduction: EGFR tyrosine kinase inhibitors have been the standard treatment for patients with NSCLC who have sensitive EGFR mutations. This study revealed final analysis survival data, biomarkers, and resistance mechanisms of osimertinib plus bevacizumab or osimertinib monotherapy in previously untreated patients with advanced EGFR-positive nonsquamous NSCLC. Methods: We previously reported the primary results of a randomized, open-label, phase 2 study comparing osimertinib plus bevacizumab with osimertinib monotherapy for this population. In this exploratory analysis using tissue and plasma samples, we evaluated gene profiles at baseline and disease progression or the last dose using targeted deep sequencing. Results: The median progression-free survival (PFS) by the blinded independent central reviewer was 22.1 months for the osimertinib plus bevacizumab arm and 20.2 months for the osimertinib arm (hazard ratio [HR] = 0.864, 95% confidence interval [CI]: 0.549–1.359). The 3-year overall survival was not different between the two arms (osimertinib plus bevacizumab: 57.1%; osimertinib monotherapy: 65.0%; HR 1.271, 95% CI: 0.727–2.223). A total of 94 patients had assessable plasma samples at baseline, and 40 had assessable pretreatment tissue samples. EGFR mutations (76.6%) and TP53 mutations (44.7%) were detected in plasma samples at baseline. In patients with plasma TP53 mutations (n = 42), the median PFS by blinded independent central reviewer was 19.8 months for the osimertinib plus bevacizumab arm and 20.2 months for the osimertinib arm (HR = 1.107, 95% CI: 0.534–2.297). Conclusions: There was also no significant difference in the PFS between the two arms, even in patients with TP53 mutations.

We present a genome assembly from an individual male Platypus cylindrus (the oak pinhole borer; Arthropoda; Insecta; Coleoptera; Curculionidae). The genome sequence is 147.5 megabases in span. Most of the assembly is scaffolded into 8 chromosomal pseudomolecules, including the X and Y sex chromosomes. The mitochondrial genome has also been assembled and is 19.29 kilobases in length. Gene annotation of this assembly on Ensembl identified 13,468 protein coding genes.

We present a genome assembly from an individual female Lochmaea capreae (the willow leaf beetle; Arthropoda; Insecta; Coleoptera; Chrysomelidae). The genome sequence is 534.7 megabases in span. Most of the assembly is scaffolded into 17 chromosomal pseudomolecules. The mitochondrial genome has also been assembled and is 18.85 kilobases in length. Gene annotation of this assembly on Ensembl identified 12,254 protein coding genes.

ABSTRACT Introduction Patients with Parkinson's disease (PD) may benefit from deep brain stimulation (DBS). Perifocal brain edema sometimes occurs after DBS surgery, but it is transient and does not affect the final prognosis. Transient deterioration of cognitive function has been reported in patients with frontal edema in the first postoperative week. This study aimed to investigate the effect of Goreisan in preventing edematous changes after DBS and determine the influence of edema on cognition. Methods We included 29 patients with PD who underwent bilateral subthalamic nucleus (STN) DBS and who were divided into 2 groups: those using (11 patients) and those not using Goreisan (18 patients). At 1 week postoperatively, all patients underwent magnetic resonance imaging. We measured the volume of edema either in the frontal white matter or STN on fluid‐attenuated inversion recovery (FLAIR) images. Finally, brain edema, motor function, and cognitive function were compared between the groups with and without Goreisan. Results In the FLAIR image 1 week postoperatively, the average postoperative frontal subcortical edema (FE) volume of the group with Goreisan was significantly lower than that without Goreisan (2249 ± 2186 mm3, 6261 ± 7213 mm3, respectively, p = 0.023). Multivariate analysis with age, preoperative Mini‐Mental State Examination (MMSE) score, FE, and peri‐STN edema (SE) as factors, and MMSE at 1 week postoperatively as the dependent variable showed that preoperative MMSE score and SE were significant as associated factors. Conclusions FE after DBS surgery may be alleviated using Goreisan. SE and preoperative MMSE scores were associated with MMSE scores 1 week postoperatively. Trial Registration Not applicable

Abstract Nonlinear gyroresonant acceleration is an essential mechanism for the formation of relativistic electrons in Earth's radiation belts, yet we still have only limited knowledge of how electron motion interacts nonlinearly with plasma waves. Here we demonstrate the compelling suppression of whistler‐mode chorus emissions as a resonant wave with energetic electrons by tuning an external transmitter signal in space plasmas. Through forcible modification of electron motions via phase trapping by the external waves, the nonlinear gyroresonant current is suppressed along with the electron hole deformation. Moreover, this can decrease the population of relativistic electrons due to the lack of coherent resonant waves seen by the phase‐organized electrons. Understanding such nonlinear wave suppression effects is crucial for a potential active control of Earth's plasma environment.

ABSTRACT Background Mutations in the epidermal growth factor receptor (EGFR) gene are the most common targetable gene alterations in non‐small cell lung cancer (NSCLC). In Japan, approximately 40% of patients who undergo surgical resection for non‐squamous NSCLC have EGFR mutations. However, no long‐term studies have been conducted including a large number of EGFR‐positive NSCLC patients with postoperative recurrence (PR). Methods We conducted a retrospective observational study of the data of EGFR‐positive NSCLC patients with PR who had undergone surgery at the Shizuoka Cancer Center between October 2002 and November 2017. We evaluated post‐recurrence overall survival (PRS) and postoperative overall survival (POS) using the Kaplan–Meier method and identify any associations between the clinical variables at recurrence and PRS using univariate and multivariate analysis. Results We enrolled 162 patients. The median observation time for PRS was 4.95 years (range, 0.82–13.25) and POS was 5.81 years (range, 2.84–16.71). The median PRS was 5.17 years (95% confidence interval [CI], 3.90–5.61) and POS was 7.07 years (95% CI, 5.88–8.01). Univariate analysis identified male sex (median PRS: 3.32 vs. 5.39 years; p

IMPORTANCE:. The relationship between post-hospital arrival factors and out-of-hospital cardiac arrest (OHCA) outcomes remains unclear. OBJECTIVES:. This study assessed the impact of post-hospital arrival factors on OHCA outcomes during the COVID-19 pandemic using a prediction model. DESIGN, SETTING, AND PARTICIPANTS:. In this cohort study, data from the All-Japan Utstein Registry, a nationwide population-based database, between 2015 and 2021 were used. A total of 541,781 patients older than 18 years old who experienced OHCA of cardiac origin were included. MAIN OUTCOMES AND MEASURES:. The primary exposure was trends in COVID-19 cases. The study compared the predicted proportion of favorable neurologic outcomes 1 month after resuscitation with the actual outcomes. Neurologic outcomes were categorized based on the Cerebral Performance Category score (1, good cerebral function; 2, moderate cerebral function). RESULTS:. The prediction model, which had an area under the curve of 0.96, closely matched actual outcomes in 2019. However, a significant discrepancy emerged after the pandemic began in 2020, where outcomes continued to deteriorate as the virus spread, exacerbated by both pre- and post-hospital arrival factors. CONCLUSIONS AND RELEVANCE:. Post-hospital arrival factors were as important as pre-hospital factors in adversely affecting the prognosis of patients following OHCA during the COVID-19 pandemic. The results suggest that the overall response of the healthcare system needs to be improved during infectious disease outbreaks to improve outcomes.

Abstract Nest-building behavior is a widely observed innate behavior. A nest provides animals with a secure environment for parenting, sleep, feeding, reproduction, and temperature maintenance. Since animal infants spend their time in a nest, nest-building behavior has been generally studied as parental behaviors, and the medial preoptic area (MPOA) neurons are known to be involved in parental nest-building. However, nest-building of singly housed male mice has been less examined. Here we show that male mice spent longer time in nest-building at the early to middle dark phase and at the end of the dark phase. These two periods are followed by sleep-rich periods. When a nest was removed and fresh nest material was introduced, both male and female mice built nests at Zeitgeber time (ZT) 6, but not at ZT12. Using Fos-immunostaining combined with double in situ hybridization of Vgat and Vglut2, we found that Vgat- and Vglut2-positive cells of the lateral preoptic area (LPOA) were the only hypothalamic neuron population that exhibited a greater number of activated cells in response to fresh nest material at ZT6, compared to being naturally awake at ZT12. Fos-positive LPOA neurons were negative for estrogen receptor 1 (Esr1). Both Vgat-positive and Vglut2-positive neurons in both the LPOA and MPOA were activated at pup retrieval by male mice. Our findings suggest the possibility that GABAergic and glutamatergic neurons in the LPOA are associated with nest-building behavior in male mice.

Background: Spatial and temporal heterogeneities of RAS and other molecular genes should be considered in the treatment of metastatic colorectal cancer (mCRC) treated with anti-epidermal growth factor receptor (EGFR) monoclonal antibodies (mAbs); acquired RAS mutation is sometimes observed at disease progression of treatment with the anti-EGFR mAb. At the same time, discrepancy of RAS status from tissues and circulating tumor DNA (ctDNA) in the same patient is sometimes observed. Based on this, we commenced two observational studies to clarify these heterogeneities of RAS and BRAF in mCRC, using next generation sequencing from liquid biopsy. Methods/Design: RAS-trace study is an observational study to monitor ctDNA RAS/BRAF/PIK3CA status every 4-12 weeks using the Plasma-SeqSensei™ CRC RUO Kit (Sysmex Inostics GmbH) in mCRC with RAS/BRAF wild-type (wt) on tumor tissue. The primary endpoint was the time to the acquired RAS mutations. A total of 42 patients has been accrued. RAS-trace-2 study is also an observational study aimed at comparing the efficacy of the anti-EGFR mAb in ctDNA RAS/BRAF wt with ctDNA RAS or BRAF mutant mCRC patients, whose RAS/BRAF are wt in tumor tissue. The primary endpoint was progression-free survival in patients with ctDNA RAS/BRAF wt and RAS or BRAF mutant. A total of 240 patients will be accrued over 2 years. Discussion: These trials will help us understanding the clinical significance of spatial and temporal heterogeneities of RAS, BRAF and other genes, while optimizing the anti-EGFR mAb treatment strategies in mCRC.

Abstract Ticks have a profound impact on public health. Haemaphysalis is one of the most widespread genera in Asia, including Japan. The taxonomy and genetic differentiation of Haemaphysalis spp. is challenging. For instance, previous studies struggled to distinguish Haemaphysalis japonica and Haemaphysalis megaspinosa due to the dearth of nucleotide sequence polymorphisms in widely used barcoding genes. The classification of H. japonica japonica and its related sub-species Haemaphysalis japonica douglasi or Haemaphysalis jezoensis is also confused due to their high morphological similarity and a lack of molecular data that support the current classification. We used mitogenomes and microbiomes of H. japonica and H. megaspinosa to gain deeper insights into the phylogenetic relationships and genetic divergence between two species. Phylogenetic analyses of concatenated nucleotide sequences of protein-coding genes and ribosomal DNA genes distinguished H. japonica and H. megaspinosa as monophyletic clades, with further subdivision within the H. japonica clade. The 16S rRNA and NAD5 genes were valuable markers for distinguishing H. japonica and H. megaspinosa. Population genetic structure analyses indicated that genetic variation within populations accounted for a large proportion of the total variation compared to variation between populations. Microbiome analyses revealed differences in alpha and beta diversity between H. japonica and H. megaspinosa: H. japonica had the higher diversity. Coxiella sp., a likely endosymbiont, was found in both Haemaphysalis species. The abundance profiles of likely endosymbionts, pathogens, and commensals differed between H. japonica and H. megaspinosa: H. megaspinosa was more diverse.

Abstract Aim The aim of this study was to clarify the significance of resection of ovarian metastases from colorectal cancer and to identify the clinicopathologic characteristics. Methods In this multicenter retrospective study, we evaluated data on ovarian metastases from colorectal cancer obtained from patients at 20 centers in Japan between 2000 and 2014. We examined the impact of resection on the prognosis of patients with ovarian metastases and examined prognostic factors. Results The study included 296 patients with ovarian metastasis. The 3‐y overall survival rate was 68.6% for solitary ovarian metastases. In all cases of this cohort, the 3‐y overall survival rates after curative resection, noncurative resection, and nonresection were 65.9%, 31.8%, and 6.1%, respectively (curative resection vs noncurative resection [P

Abstract We designed this multi-center prospective study with the following objectives: (1) the cross-sectional validation of extracellular vesicles (EV) mRNA markers to detect urothelial bladder cancer (UBC) before transurethral resection of bladder cancer (TURBT), and (2) the longitudinal validation of EV mRNA markers to monitor non-muscle invasive bladder cancer (NMIBC) recurrence after TURBT. EV mRNA markers evaluated in this study were KRT17, GPRC5A, and SLC2A1 in addition to two additional markers from literatures, MDK and CXCR2, and measured by quantitative RT-PCR with normalization by a reference gene (ALDOB). Diagnostic performances of EV mRNA markers were compared to conventional markers. Regarding the first objective, we confirmed that EV mRNA biomarkers in urine were higher in UBC patients, particularly those with higher stage/grade tumors, than in those without UBC (n = 278 in total) and the diagnostic performance of EV mRNA MDK and KRT17 outperformed conventional biomarkers with AUC 0.760 and 0.730, respectively. Concerning the second objective, we prospectively analyzed the time courses of EV mRNA markers while NMIBC patients (n = 189) (median follow-up 19 months). The expression of EV mRNA KRT17 was significantly high in patients with recurrence, while it gradually decreased over time in those without recurrence (p

Opportunistic networks are characterized by intermittent connectivity and dynamic topologies, which pose significant challenges for efficient message delivery, resource management, and routing decision-making. This paper introduces the Fuzzy Control Routing Protocol, a novel approach designed to address these challenges by leveraging fuzzy logic to enhance routing decisions and improve overall network performance. The protocol considers buffer occupancy, angle to destination, and the number of unique connections of the target nodes to make context-aware routing decisions. It was implemented and evaluated using the FuzzyC framework for simulations and the opportunistic network environment simulator for realistic network scenarios. Simulation results demonstrate that the Fuzzy Control Routing Protocol achieves competitive delivery probability, efficient resource utilization, and low overhead compared to the Epidemic and MaxProp protocols. Notably, it consistently outperformed the Epidemic protocol across all metrics and exhibited comparable delivery probability to MaxProp while maintaining significantly lower overhead, particularly in low-density scenarios. The results demonstrate the protocol’s ability to adapt to varying network conditions, effectively balance forwarding and resource management, and maintain robust performance in dynamic vehicular environments.