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Abstract Background It is widely recognized that periodontal disease is associated with diabetes mellitus. Periodontal disease is accompanied by inflammation of the periodontal tissue, impaired masticatory function, and the presence of periodontopathic bacteria, all of which may affect glycemic control. However, the exact relationship between these factors and glycemic control has not yet been established. In this study, we aimed to investigate the relationship between periodontal disease-related factors and glycemic control in Japanese community-dwelling individuals. Methods We conducted a cross-sectional study involving 671 participants aged 29–92 (65.3 ± 12.1) years, using data from the Nagasaki Islands Study. Participants underwent routine medical examinations, including body mass index (BMI) and hemoglobin A1c (HbA1c) levels. Information on the participants’ demographics (age and sex) and whether they were on diabetes medications, had an exercise habit, consumed alcohol, engaged in late-night eating, had regular dental checkups, and smoked was obtained using a self-administered questionnaire. Dental examinations were performed to examine dentition status, probing pocket depth, clinical attachment level (CAL), and bleeding on probing. Functional tooth units (FTUs), defined as pairs of occluding posterior teeth, were used as an indicator of occlusal support area. Saliva samples were collected and levels of two species of periodontopathic bacteria (Porphyromonas gingivalis and Aggregatibacter actinomycetemcomitans) were determined using real-time polymerase chain reaction. We analyzed the association between HbA1c levels and variables related to periodontal status, masticatory function, and salivary levels of periodontopathic bacteria. Results Bivariate analysis showed that HbA1c levels were significantly associated with age, sex, exercise habit, BMI, diabetes medications, CAL, salivary P. gingivalis level, number of teeth, and three FTU subcategories. In the multiple regression analysis, age, BMI, diabetes medications, and total FTU score (i.e., including natural teeth, implant-supported artificial teeth, fixed prostheses, and removable dentures) remained associated with HbA1c levels (B = 0.23, 0.14, 0.52, and − 0.12; p

Abstract Background The perioperative use of the Impella 5.5 has been increasing recently; however, the left ventricular perforation by this device during surgery has not been reported to date. Case presentation Postinfarction ventricular septal rupture in a 75-year-old man was successfully repaired with support of a single Impella 5.5 device used for consecutive 28 days perioperatively. The patient underwent surgery after 16 days of Impella support. During surgery, the Impella was left in place expecting its use for left ventricular unloading after the operation. After aortic cross-clamp, when the apex was carefully lifted, the tip of the Impella almost protruded from the posterior wall, and could be seen through the epicardium. The aorta was unclamped briefly, the Impella was pulled out several centimeters, and the aorta was cross-clamped again. The ventricular septal rupture was repaired by the double-layer patch technique via the right ventricle. Immediately before the chest closure, the free wall of the LV ruptured and blood rapidly flowed out. It was where the Impella almost protruded during cardiac arrest, and was repaired with a pledgeted monofilament mattress suture. Conclusions A single device can be used throughout perioperative periods; however, if used during surgery, possible risk of left ventricular perforation should be well recognized since the device has no soft pigtail part at its end, and its stiff tip can directly contact the decompressed, flaccid ventricular wall during cardiac arrest.

(1) Background: The number of patients with cancer undergoing cancer genome profiling is increasing; however, it remains unclear how accurately they understand the details of the tests and treatments. This study aimed to clarify the awareness of cancer genome profiling tests among patients with cancer who visited cancer genome medical clinics. (2) Methods: A questionnaire survey was conducted on awareness, anxiety, sources of information, and psychological states concerning cancer genome profiling tests. (3) Results: In total, 265 patients with cancer (117 men, 142 women, 6 no response, average age of 58.29 ± 11.9 years) were included in the study, of which 218 (82.3%) were aware of the term “cancer genomic medicine” and 90 (34.0%) were aware of its details. Thus, only a few respondents understood that cancer genome profiling tests facilitate the discovery of secondary findings and of genes associated with hereditary tumors. Regarding their psychological state when visiting the cancer genome clinic, the respondents were anxious about standard treatment and prognosis limits. (4) Conclusions: From the viewpoint of advance care planning, we suggest that medical professionals build a support system that links palliative care and cancer treatment and coordinates genetic counseling at an early stage.

Objective This article evaluates the ability of low-energy (40 keV) virtual monoenergetic images (VMIs) in the local diagnosis of cervical cancer compared with that of conventional computed tomography (C-CT) and magnetic resonance imaging (MRI), using clinicopathologic staging as a reference.

We isolated highly pathogenic avian influenza (HPAI) H5N5 and H5N1 viruses from crows in Hokkaido, Japan, during winter 2023–24. They shared genetic similarity with HPAI H5N5 viruses from northern Europe but differed from those in Asia. Continuous monitoring and rapid information sharing between countries are needed to prevent HPAI virus transmission.

Background: Molluscum contagiosum (MC) is a contagious viral skin infection. Berdazimer gel, 10.3% (SB206 12%) is approved in the United States as the first topical, at-home MC prescription medication. Objective: To assess safety and tolerability of SB206 12% in Japanese patients with MC. Methods: SKN15B01 (JRCT2031230123) was a phase 2, multicenter, single-group, open-label study in Japanese patients ≥2 years old with 3-70 baseline MC lesions. Patients with only periocular MC and/or immunosuppression were excluded. SB206 12% was applied once daily to lesions for 12 weeks. Safety endpoints included adverse events and local skin reactions. Exploratory efficacy endpoints included percentage of patients with complete lesion clearance and lesion count percent change from baseline. Results: Twenty patients (12 males, 8 females) with mean (range) age of 5.2 (3-13) years and mean (range) baseline lesion counts of 22.5 (8-44). Complete clearance and percent change from baseline at week 12 were 60% and −89.2%, respectively. The most common treatment-related adverse events were application site-erythema (25%, n = 5), -pain (25%, n = 5), -pruritis (25%, n = 5), and -dermatitis (20%, n = 4), all mild/moderate in severity. Limitations: Single-group study; small sample size. Conclusion: Safety and efficacy of berdazimer gel, 10.3% in Japanese patients were favorable and consistent with previous studies.

Mucosa-associated lymphoid tissue (MALT) lymphoma commonly arises from chronic inflammation or autoimmune diseases, such as Sjögren syndrome (SjS). Although rare, amyloid deposition in MALT lymphoma has been reported. We present a rare case of parotid gland MALT lymphoma in a 49-year-old woman, in whom preoperative diagnosis was challenging due to atypical imaging findings resulting from amyloid deposits. MRI showed T2-hypointense and T1-iso- to slightly hyperintense masses in the left parotid gland and right sublingual gland, with predominant marginal contrast enhancement and no significant diffusion restriction. Additionally, atrophy and fatty replacement of the parenchyma were noted in bilateral parotid glands, suggesting SjS. Left superficial parotidectomy was performed and pathological findings confirmed MALT lymphoma with extensive amyloid deposition. Histopathological findings of the resected parotid gland parenchyma also suggested SjS. MALT lymphoma should be considered in the differential diagnosis of multiple salivary gland masses in patients with suspected SjS. If MRI reveals atypical imaging findings for malignant lymphoma, particularly T2-hypointensity with no significant diffusion restriction, the possibility of amyloid deposition in MALT lymphoma should be considered.

Background /purpose: The standard treatment for medication-related osteonecrosis of the jaw (MRONJ) is surgery. However, reports on the appropriate extent of bone resection are few. We aimed to examine the relationship between the extent of bone resection and postoperative outcomes in patients with mandibular MRONJ. Materials and methods: The clinical and imaging findings and treatment outcomes of 206 patients (258 surgeries) with mandibular MRONJ undergoing surgery were reviewed. Imaging findings were evaluated using computed tomography (CT) to sequestrum, osteolysis, periosteal reaction, and mixed-type osteosclerosis, and determine the extent of resection. In some cases, samples were taken from within the bone, and real-time polymerase chain reaction was used to confirm the presence of bacteria and fungi. Results: The three-year cumulative cure rate was 81.7%. Patients with malignant tumors showing no osteolysis and undergoing sequestrum removal or marginal mandibulectomy had significantly worse prognosis than those with osteoporosis showing osteolysis and undergoing segmental mandibulectomy. Furthermore, patients with residual osteolysis, periosteal reactions, and mixed-type osteosclerosis on CT were more likely to develop recurrence. Eleven patients showed no osteolysis on CT images. Patients with cancer administered with high-dose denosumab had significantly poorer prognosis. Bacteria and fungi were also detected in samples obtained from gap-type periosteal reaction and mixed-type osteosclerosis. Conclusion: Surgery for MRONJ requires resection of the infected bone. Aside from the osteolysis area, the gap-/irregular-type periosteal reaction and mixed-type osteosclerosis must also be included in the resection area. Methods for determining the extent of bone resection in MRONJ without osteolysis are a future challenge.

There is a lack of data regarding the safety and effectiveness of implanting the Pipeline Embolization Device with Shield technology (PED-Shield) compared with the previous generation of Pipeline (PED-Flex). This retrospective single-center study aimed to compare treatment outcomes between the PED-Shield and PED-Flex for treating unruptured internal carotid artery aneurysms. The PED-Flex was used in 62 procedures (67 aneurysms, 59 patients) and the PED-Shield in 53 procedures (59 aneurysms, 58 patients). The mean aneurysm diameter was significantly lower in the PED-Shield group than in the PED-Flex group (11.9 ± 7.0 mm vs. 15.2 ± 6.9 mm, p < 0.001). At the 12-month follow-up, the complete angiographic occlusion rate was 72.1% and 72.3% in the PED-Flex and PED-Shield groups, respectively (p = 0.9808). Limited to aneurysms larger than 10 mm, 70.6% and 68.0%, respectively (p = 0.8175). The incidence of more than three high signal intensity areas on diffusion-weighted imaging after treatment was significantly lower in the PED-Shield group than in the PED-Flex group (27.7% vs. 67.7%; p < 0.001). Limited to aneurysms larger than 10 mm, 41.1% and 69.6%, respectively (p < 0.0117). Symptomatic ischemic complications occurred within 30 days of four PED-Flex procedures (6.5%) and one PED-Shield procedure (2.0%) (p = 0.2315). Limited to aneurysms larger than 10 mm, 1.8% and 3.2%, respectively (p = 0.6677). The incidence of mRS score worsening at 6 months was 3.2% and 1.9% in the PED-Flex and PED-Shield groups, respectively (p = 0.6534). The PED-Shield can achieve outcomes equivalent to or better than the PED-Flex. Further large-scale studies are warranted to confirm our findings.

Abstract The COVID-19 pandemic has increased germ aversion, an aversive affective response to a high likelihood of pathogen transmission. While psychological factors are associated with chronic pain, the relationship between germ aversion and chronic pain remains unexplored. This study aimed to examine the relationship between germ aversion and new-onset and prognosis of chronic pain using longitudinal data collected during the COVID-19 pandemic. We conducted web-based surveys of full-time workers at baseline and after three months. Data were collected on demographic characteristics, psychological factors, and chronic pain. Germ aversion was assessed using a modified Perceived Vulnerability to Disease scale. We analyzed responses from 1265 panelists who completed the survey twice. The prevalence of chronic low back pain (CLBP) and chronic neck and shoulder pain (CNSP) was associated with sex, short sleep duration, psychological distress, loneliness, and germ aversion. Stratified analyses showed that germ aversion was a risk factor for CLBP at three months in both individuals with and without CLBP at baseline, and for CNSP at three months in those with CNSP at baseline, even after adjustment for confounders. In conclusion, this preliminary study suggests that high germ aversion is a risk factor for CLBP and CNSP in young and middle-aged workers.

Abstract Unlike plants in the field, which experience significant temporal fluctuations in environmental conditions, plants in the laboratory are typically grown in controlled, stable environments. Therefore, signaling pathways evolved for survival in fluctuating environments often remain functionally latent in laboratory settings. Here, we show that TGA1 and TGA4 act as hub transcription factors through which the expression of genes involved in high-affinity nitrate uptake are regulated in response to shoot-derived phloem mobile polypeptides, CEP DOWNSTREAM 1 (CEPD1), CEPD2 and CEPD-like 2 (CEPDL2) as nitrogen (N) deficiency signals, and Glutaredoxin S1 (GrxS1) to GrxS8 as N sufficiency signals. CEPD1/2/CEPDL2 and GrxS1-S8 competitively bind to TGA1/4 in roots, with the former acting as transcription coactivators that enhance the uptake of nitrate, while the latter function as corepressor complexes together with TOPLESS (TPL), TPL-related 1 (TPR1) and TPR4 to limit nitrate uptake. Arabidopsis plants deficient in TGA1/4 maintain basal nitrate uptake and exhibit growth similar to wild-type plants in a stable N environment, but are impaired in regulation of nitrate acquisition in response to shoot N demand, leading to defective growth under fluctuating N environments where rhizosphere nitrate ions switch periodically between deficient and sufficient states. TGA1/4 are crucial transcription factors that enable plants to survive under fluctuating and challenging N environmental conditions.

Abstract Missed appointments, or no-shows, disrupt healthcare delivery, exacerbating chronic disease management and leading to worse health outcomes. Telehealth has surged as a viable solution to reduce no-shows and improve healthcare accessibility, especially during the COVID-19 pandemic. However, telehealth disparities and its long-term efficacy across various medical specialties remain understudied. To address this, we performed a retrospective analysis of electronic health records from a heterogenous network of hospitals in Illinois, examining telehealth use and no-shows across among 444,752 adult patients with 1,973,098 outpatient encounters across nine specialties during the sustained pandemic phase (i.e., January 1, 2021 to July 1, 2022). Among them, 84,290 (4.27%) were no-shows, and telehealth constituted 202,933 (10.3%) of the total encounters. Telehealth use during the sustained phase varied significantly by specialty type. Overall, telehealth encounters were associated with reduced no-show odds compared to in-person encounters (OR, 0.28; 95% CI, 0.26–0.29). Black and Hispanic patients, as well as those with Medicaid, had higher no-show odds relative to their counterparts, even when using telehealth. Mental health specialty had the highest telehealth usage rate and the highest no-show odds (OR, 2.99; 95% CI, 2.84–3.14) relative to other specialties included in the study. Moreover, specialty type had differential effects on no-shows for telehealth. These results underscore the variability in telehealth use by specialty type and pervasive disparities telehealth use and no-shows. As we move beyond the pandemic, our findings can inform policymakers to tailor policies and incentives to reach different patient groups as well as specialties, with varying needs, to promote equitable telehealth utilization.

Abstract Background Migrants are individuals who move to a different country from their usual place of residence. Japan’s migrant population, particularly technical interns and students, has been growing. Even before the pandemic, previous studies have highlighted difficulties faced by migrants in utilizing healthcare services. This study examined the uptake of COVID-19 vaccination, testing, and medical care among Myanmar migrants in Japan; identified the factors associated with this uptake; and described the difficulties encountered when utilizing these services. Methods A cross-sectional study was conducted between March and April 2023 targeting Myanmar migrants over 18 years residing in Japan for more than 6 months. An online self-administered questionnaire in Myanmar language covered socioeconomic characteristics; history of COVID-19 vaccination, testing, and medical care; and difficulties encountered while utilizing these services with multiple-choice questions. Multivariate logistic regression analysis was performed separately to identify the factors associated with the uptake of COVID-19 vaccination, testing, and medical care. Results Among the 207 participants, 52% (n = 108) were under 30 years, 30% (n = 62) were male, and 31% (n = 65) were low-skilled workers (technical interns and students). Overall, 91% (n = 189) had received the COVID-19 vaccination, 76% (n = 157) had been tested for COVID-19, and 43% (n = 68) tested positive. However, only 77% (n = 52) of COVID-19 patients sought medical care. Participants under 30 years of age were less likely to receive the COVID-19 vaccine compared to those aged 30 and older (adjusted odds ratio [aOR] 0.10, 95% confidence interval [CI] 0.01–0.88, p = 0.038). Low-skilled workers were less likely to seek medical care compared to those holding other categories of residential status (aOR 0.12, 95% CI 0.02–0.79, p = 0.027). Among service users, 5% faced difficulties with COVID-19 vaccination, 10% with testing, and 17% with receiving medical care. Long waiting times and complex reservation processes were the main difficulties encountered. Conclusions The uptake of COVID-19 vaccination, testing, and medical care in this sample was reasonably good. However, individuals under 30 years of age showed lower uptake of vaccination, while low-skilled workers had lower uptake of medical care. Strengthening education and support for young migrants and low-skilled workers regarding COVID-19 and other infectious diseases is essential, especially in workplaces and educational institutions.

Integrating autonomous vehicles (AVs) into public roads presents profound implications for pedestrian safety and the broader acceptance of this emerging technology. This work examines the complex interactions between AVs and pedestrians, a dynamic influenced by the variability of pedestrian behaviors and the absence of traditional communication mechanisms, such as eye contact and gestures, commonly relied upon in human-driven scenarios. Given the nascent stage of AV deployment, this research addresses the challenges of evaluating AV−pedestrian interactions amid safety concerns and technological limitations. We review and synthesize global research on pedestrian behavior in the context of AV technology to track changes in pedestrians’ acceptance over time and identify the factors driving these shifts. Additionally, this review incorporates insights from transportation authorities to highlight potential safety issues and the need for innovative communication strategies that ensure safe interactions between pedestrians and AVs. By analyzing these factors, the research aims to contribute to the development of guidelines and communication protocols that enhance pedestrian safety and facilitate the integration of AVs into urban environments.

Abstract Pathogens of the enterovirus genus, including poliovirus and coxsackieviruses, typically circulate in the summer months suggesting a possible positive association between warmer weather and transmission. Here we evaluate the environmental and demographic drivers of enterovirus transmission, as well as the implications of climate change for future enterovirus circulation. We leverage pre-vaccination era data on polio in the US as well as data on two enterovirus A serotypes in China and Japan that are known to cause hand, foot, and mouth disease. Using mechanistic modeling and statistical approaches, we find that enterovirus transmission appears positively correlated with temperature although demographic factors, particularly the timing of school semesters, remain important. We use temperature projections from Coupled Model Intercomparison Project Phase 6 (CMIP6) to simulate future outbreaks under late 21st-century climate change for Chinese provinces. We find that outbreak size increases with climate change on average, though results differ across climate models depending on the degree of wintertime warming. In the worst-case scenario, we project peak outbreaks in some locations could increase by up to 40%.

Abstract Background Among the oral antivirals used for treating patients with mild-to-moderate novel coronavirus disease 2019 (COVID-19), nirmatrelvir/ritonavir (NMV/RTV) and ensitrelvir (ESV) are inhibitors of cytochrome P450 (CYP) 3A, and therefore, can cause drug–drug interactions with concomitant medications. Tacrolimus (TAC), a substrate of CYP3A4/5, is administered for a long period to prevent rejection after kidney transplantation. TAC should be discontinued while using NMV/RTV because blood TAC levels significantly increase when these drugs are concomitantly administered. However, the influence of ESV on blood TAC levels has not yet been reported, and the management of TAC doses during the use of ESV remains unclear. Case presentation We experienced three kidney transplant recipients with COVID-19, whose blood trough levels of TAC increased by the concomitant use of NMV/RTV or ESV. In two patients administering NMV/RTV, blood trough levels of TAC increased more than tenfold after combination therapy, whereas in one patient administering ESV, TAC level increased approximately threefold. Conclusions These cases suggest that TAC administration should be discontinued during NMV/RTV treatment to maintain blood TAC levels within the therapeutic range, and a reduced TAC dose is sufficient during ESV treatment.

Objective: To demonstrate the effect of intraovarian injection of lyophilized platelet-rich plasma (PRP) in poor ovarian responders. Methods: This retrospective cohort study evaluated data for 262 women who underwent intraovarian injection of lyophilized PRP at two private fertility clinics. Women treated from December 2021 to September 2022 and who met the Bologna criteria were included. Intraovarian injection of lyophilized PRP prepared from 50[Formula: see text]mL of autologous peripheral blood was followed by two centrifugations and activation with 2% CaCl2, in which cells were removed with a filter and stored at room temperature. The differences in the follicle-stimulating hormone and antral follicle count (AFC), and the number of retrieved oocytes, mature oocytes, fertilized embryos, cleavage embryos, and blastocysts were measured before and 3 months after a single injection. A biological pregnancy with embryos generated after injection was also examined. Results: Patients’ median age and anti-Mullerian hormone (AMH) levels were 44 years and 0.38[Formula: see text]ng/mL, respectively. The number of retrieved oocytes or mature oocytes and fertilized embryos or cleavage embryos was higher after injection. The number of cleavage embryos in women [Formula: see text] years significantly increased after injection. Of the 262 patients who underwent intraovarian injection of lyophilized PRP, 71 underwent embryo transfers using embryos obtained 3 months after injection, and 14 had biological pregnancies. Seven of these patients were in their 40s. Out of 14, one had a live birth, six are ongoing pregnancies, six had chemical abortions, and one had a miscarriage. Conclusions: Intraovarian injection of lyophilized PRP improved egg retrieval results, especially in patients older than 40 years. Furthermore, this treatment may contribute to biological pregnancy in patient with poor ovarian response but needs to be further investigated in more cases in the future.

We determined the complete mitochondrial DNA sequence of a Biwa goby, Gymnogobius isaza (Tanaka, 1916) using next-generation sequencing methods. The composition of its mitogenome is the same as that observed in most other vertebrates, comprising of 13 protein-coding genes, 22 tRNA genes, two rRNA genes, and two control regions. Our molecular phylogenetic analysis confirmed the close phylogenetic relationship between G. isaza and G. petschiliensis. This mitogenome information will be useful for distribution surveys using environmental DNA and the development of conservation strategies for this species.

Abstract Memory T cells demonstrate superior in vivo persistence and antitumor efficacy. However, methods for manufacturing less differentiated T cells are not yet well-established. Here, we show that producing chimeric antigen receptor (CAR)-T cells using berbamine (BBM), a natural compound found in the Chinese herbal medicine Berberis amurensis, enhances the antitumor efficacy of CAR-T cells. BBM is identified through cell-based screening of chemical compounds using induced pluripotent stem cell-derived T cells, leading to improved viability with a memory T cell phenotype. Transcriptomics and metabolomics using stem cell memory T cells reveal that BBM broadly enhances lipid metabolism. Furthermore, the addition of BBM downregulates the phosphorylation of p38 mitogen-activated protein kinase and enhanced mitochondrial respiration. CD19-CAR-T cells cultured with BBM also extend the survival of leukaemia mouse models due to their superior in vivo persistence. This technology offers a straightforward approach to enhancing the antitumor efficacy of CAR-T cells.

Abstract Many slow slip events (SSEs) occur beneath the ocean, and continuous ocean‐bottom pressure gauge (OBP) observations provide useful data. OBPs record both oceanic variations and crustal movements, so we developed a multi‐channel singular spectrum analysis method to remove oceanic variations and applied our method to OBPs and oceanic model data. Then components of the oceanic model with good correlations to the OBP data were subtracted from the observed data. This method compensates for the incompleteness of the oceanic model and removes oceanic variations better than use of the original model. We applied the method to OBP data for the 2018 Boso, Japan, SSE to estimate its slip distribution. Comparing slip distributions obtained with and without the OBP data, we found that the distribution obtained using OBP data extended further offshore, and the offshore estimation error was smaller. Our study shows that offshore observations using OBPs are important for characterizing SSEs.

ABSTRACT In vivo imaging of bacterial infection models enables noninvasive and temporal analysis of individuals, enhancing our understanding of infectious disease pathogenesis. Conventional in vivo imaging methods for bacterial infection models involve the insertion of the bacterial luciferase LuxCDABE into the bacterial genome, followed by imaging using an expensive ultrasensitive charge-coupled device (CCD) camera. However, issues such as limited light penetration into the body and lack of versatility have been encountered. We focused on near-infrared (NIR) light, which penetrates the body effectively, and attempted to establish an in vivo imaging method to evaluate the number of lung-colonizing bacteria during the course of bacterial pneumonia. This was achieved by employing a novel versatile system that combines plasmid-expressing firefly luciferase bacteria, NIR substrate, and an inexpensive, scientific complementary metal-oxide semiconductor (sCMOS) camera. The D-luciferin derivative “TokeOni,” capable of emitting NIR bioluminescence, was utilized in a mouse lung infection model of Acinetobacter baumannii, an opportunistic pathogen that causes pneumonia and is a concern due to drug resistance. TokeOni exhibited the highest sensitivity in detecting bacteria colonizing the mouse lungs compared with other detection systems such as LuxCDABE, enabling the monitoring of changes in bacterial numbers over time and the assessment of antimicrobial agent efficacy. Additionally, it was effective in detecting A. baumannii clinical isolates and Klebsiella pneumoniae. The results of this study are expected to be used in the analysis of animal models of infectious diseases for assessing the efficacy of therapeutic agents and understanding disease pathogenesis.IMPORTANCEConventional animal models of infectious diseases have traditionally relied upon average assessments involving numerous individuals, meaning they do not directly reflect changes in the pathology of an individual. Moreover, in recent years, ethical concerns have resulted in the demand to reduce the number of animals used in such models. Although in vivo imaging offers an effective approach for longitudinally evaluating the pathogenesis of infectious diseases in individual animals, a standardized method has not yet been established. To our knowledge, this study is the first to develop a highly versatile in vivo pulmonary bacterial quantification system utilizing near-infrared luminescence, plasmid-mediated expression of firefly luciferase in bacteria, and a scientific complementary metal-oxide semiconductor camera. Our research holds promise as a useful tool for assessing the efficacy of therapeutic drugs and pathogenesis of infectious diseases.

Acidic oral environments may trigger systemic contact dermatitis via ionization of metals, including palladium. A patch test revealed a late delayed positive response to palladium, emphasizing the need for nuanced diagnostic approaches for allergy management.

Pectin, a soluble fiber, can induce elongation of the intestinal villi. However, the relationship between pectin-induced villus elongation and nutrient absorption remains unclear. Therefore, we investigated whether pectin could mitigate malnutrition by enhancing nutrient absorption. We specifically utilized Yuzu pectin side chains, which were chosen for their potential in preventing nutrient absorption inhibition, to examine their effects on elongation of the villus in protein-deficient, mildly malnourished mice. These side chains exerted contrasting effects on the spleen and liver, both of which atrophied owing to a low-protein diet, preventing a decrease in spleen weight. The administration of side chains suppressed liver lipid accumulation; however, triglyceride and cholesterol levels were increased. Although these side chains extended the jejunal villi, they could not completely alleviate malnutrition. This study establishes a crucial foundation for further elucidating the physiological relevance of the pectin-induced morphological alterations in the small intestinal villus and advancing its practical applications.

Although some Mendelian neurodevelopmental disorders have been shown to entail specific DNA methylation changes designated as epi-signatures, it remains unknown whether epi-signatures are consistent features of other genetic disorders. Here, we analyzed DNA methylation profiles of patients with hypogonadotropic hypogonadism (HH), a rare neuroendocrine disorder typically caused by monogenic or oligogenic mutations. First, we performed microarray-based genome-wide methylation analyses of nine patients with HH due to ANOS1, SOX2, or SOX10 variants and 12 control individuals. The results showed that 1118 probes were differentially methylated in one or more patients. The differentially methylated probes were highly variable among patients. No significant methylation changes were observed in genes functionally associated with ANOS1, SOX2, or SOX10. Then, we performed pyrosequencing of six selected CpG sites in the nine patients and 35 additional HH patients. The results of the patients were compared with those of 48 fertile men. There were no common methylation changes among these patients, with the exception of hypermethylation of two CpG sites in the ZNF245 promoter of three patients. Hypermethylation of the promoter has previously been reported as a very rare epigenetic polymorphism in the general population. These results indicate that genomes of HH patients have considerable DNA methylation changes; however, these changes are more likely to be physiological epigenetic variations than disease-specific epi-signatures. Our data suggest a possible association between hypermethylation of the ZNF254 promoter and HH, which needs to be examined in future studies.

High pathogenicity avian influenza viruses (HPAIVs) of the H5N1 and H5N2 subtypes were responsible for 84 HPAI outbreaks on poultry premises in Japan during October 2022–April 2023. The number of outbreaks during the winter of 2022–2023 is the largest ever reported in Japan. In this study, we performed phylogenetic analyses using the full genetic sequences of HPAIVs isolated in Japan during 2022–2023 and those obtained from a public database to identify their genetic origin. Based on the hemagglutinin genes, these HPAIVs were classified into the G2 group of clade 2.3.4.4b, whose ancestors were H5 HPAIVs that circulated in Europe in late 2020, and were then further divided into three subgroups (G2b, G2d, and G2c). Approximately one-third of these viruses were classified into the G2b and G2d groups, which also included H5N1 HPAIVs detected in Japan during 2021–2022. In contrast, the remaining two-thirds were classified into the G2c group, which originated from H5N1 HPAIVs isolated in Asian countries and Russia during the winter of 2021–2022. Unlike the G2b and G2d viruses, the G2c viruses were first detected in Japan in the fall of 2022. Importantly, G2c viruses caused the largest number of outbreaks throughout Japan over the longest period during the season. Phylogenetic analyses using eight segment genes revealed that G2b, G2d, and G2c viruses were divided into 2, 4, and 11 genotypes, respectively, because they have various internal genes closely related to those of avian influenza viruses detected in wild birds in recent years in Asia, Russia, and North America, respectively. These results suggest that HPAIVs were disseminated among migratory birds, which may have generated numerous reassortant viruses with various gene constellations, resulting in a considerable number of outbreaks during the winter of 2022–2023.

Abstract Epitope binning, an approach for grouping antibodies based on epitope similarities, is a critical step in antibody drug discovery. However, conventional methods are complex, involving individual antibody production. Here, we established Epitope Binning-seq, an epitope binning platform for simultaneously analyzing multiple antibodies. In this system, epitope similarity between the query antibodies (qAbs) displayed on antigen-expressing cells and a fluorescently labeled reference antibody (rAb) targeting a desired epitope is analyzed by flow cytometry. The qAbs with epitope similar to the rAb can be identified by next-generation sequencing analysis of fluorescence-negative cells. Sensitivity and reliability of this system are confirmed using rAbs, pertuzumab and trastuzumab, which target human epidermal growth factor receptor 2. Epitope Binning-seq enables simultaneous epitope evaluation of 14 qAbs at various abundances in libraries, grouping them into respective epitope bins. This versatile platform is applicable to diverse antibodies and antigens, potentially expediting the identification of clinically useful antibodies.

Abstract Background The COVID-19 pandemic, caused by SARS-CoV-2, was one of the greatest modern public health crises that the world has faced. Countries undertook sweeping public health and social measures (PHSM); including environmental actions such as disinfection and ventilation; surveillance and response, such as contact tracing and quarantine; physical, such as crowd control; and restrictions on travel. This study focuses on the public perceptions of PHSM in two countries, Japan and the United Kingdom (UK) as examples of high-income countries that adopted different measures over the course of the pandemic. Methods This study was conducted between November 2021 and February 2022, a period in which the Omicron variant of SARS-CoV-2 was predominant. Fourteen online focus group discussions were conducted in each country. Overall, 106 total participants (50 from the UK and 56 from Japan) participated in 23 focus groups (11 in the UK and 12 in Japan) with an average of three to six participants per group. Both countries were compared using a thematic analysis method. Results Both countries’ participants agreed that vaccination was an effective measure. However, they did not favor mandatory vaccination policies. Working from home was well accepted by both sides, but they reported that schools should have continued to be opened as before COVID-19. Both sides of participants expressed that temperature testing alone in indoor facilities was ineffective as a COVID-19 control measure. There were contrasting views on face covering rules in public spaces, international and domestic movement restrictions. High acceptance of mask-wearing was reflective of Japanese customs, while it was accepted as a strong recommendation for participants in the UK. Japanese participants favored quarantine for international travel, while the UK participants supported banning non-essential travel. Conclusion Similar and contrasting views on PHSM against COVID-19 between Japan and the UK demonstrated how policies in controlling an epidemic should be tailored by country with respect to its norms, cultures, economic and disease burden. Our findings may guide how policy makers can engage with the public through effective health communication and consider regulations that are aligned with the public’s views and capacities in changing their behavior for future pandemic preparedness.

Abstract This study performed three-dimensional (3D) magnetic resonance imaging (MRI)-based statistical shape analysis (SSA) by comparing patellofemoral instability (PFI) and normal femur models, and developed a machine learning (ML)-based prediction model. Twenty (19 patients) and 31 MRI scans (30 patients) of femurs with PFI and normal femurs, respectively, were used. Bone and cartilage segmentation of the distal femurs was performed and subsequently converted into 3D reconstructed models. The pointwise distance map showed anterior elevation of the trochlea, particularly at the central floor of the proximal trochlea, in the PFI models compared with the normal models. Principal component analysis examined shape variations in the PFI group, and several principal components exhibited shape variations in the trochlear floor and intercondylar width. Multivariate analysis showed that these shape components were significantly correlated with the PFI/non-PFI distinction after adjusting for age and sex. Our ML-based prediction model for PFI achieved a strong predictive performance with an accuracy of 0.909 ± 0.015, and an area under the curve of 0.939 ± 0.009 when using a support vector machine with a linear kernel. This study demonstrated that 3D MRI-based SSA can realistically visualize statistical results on surface models and may facilitate the understanding of complex shape features.

Abstract In gram-negative bacteria, IS26 often exists in multidrug resistance (MDR) regions, forming a pseudocompound transposon (PCTn) that can be tandemly amplified. It also generates a circular intermediate called the “translocatable unit (TU)”, but the TU has been detected only by PCR. Here, we demonstrate that in a Klebsiella pneumoniae MDR clone, mono- and multimeric forms of the TU were generated from the PCTn in a preexisting MDR plasmid where the inserted form of the TU was also tandemly amplified. The two modes of amplification were reproduced by culturing the original clone under antimicrobial selection pressure, and the amplified state was maintained in the absence of antibiotics. Mono- and multimeric forms of the circularized TU were generated in a RecA-dependent manner from the tandemly amplified TU, which can be generated in RecA-dependent and independent manners. These findings provide novel insights into the dynamic processes of genome amplification in bacteria.

Abstract Chronic obstructive pulmonary disease (COPD) is a progressive disease that is characterized by chronic airway inflammation. A Japanese herbal medicine, hochuekkito (TJ-41), is prominently used for chronic inflammatory diseases in Japan. This study aimed to analyze the anti-inflammatory effect of TJ-41 in vivo and its underlying mechanisms. We created a COPD mouse model using intratracheal administration of porcine pancreatic elastase and lipopolysaccharide (LPS) and analyzed them with and without TJ-41 administration. A TJ-41-containing diet reduced inflammatory cell infiltration of the lungs in the acute and chronic phases and body weight loss in the acute phase. In vitro experiments revealed that TJ-41 treatment suppressed the LPS-induced inflammatory cytokines in BEAS-2B cells. Furthermore, TJ-41 administration activated the AMP-activated protein kinase (AMPK) pathway and inhibited the mechanistic target of the rapamycin (mTOR) pathway, both in cellular and mouse experiments. We concluded that TJ-41 administration reduced airway inflammation in the COPD mouse model, which might be regulated by the activated AMPK pathway, and inhibited the mTOR pathway.

Abstract Plants initiate specific defense responses by recognizing conserved epitope peptides within the flagellin proteins derived from bacteria. Proteolytic cleavage of epitope peptides from flagellin by plant apoplastic proteases is thought to be crucial for the perception of the epitope by the plant receptor. However, the identity of the plant proteases involved in this process remains unknown. Here, we establish an efficient identification system for the target proteases in Arabidopsis apoplastic fluid; the method employs native two-dimensional electrophoresis followed by an in-gel proteolytic assay using a fluorescence-quenching peptide substrate. We designed a substrate to specifically detect proteolytic activity at the C-terminus of the flg22 epitope in flagellin and identified two plant subtilases, SBT5.2 and SBT1.7, as specific proteases responsible for the C-terminal cleavage of flg22. In the apoplastic fluid of Arabidopsis mutant plants deficient in these two proteases, we observe a decrease in the C-terminal cleavage of the flg22 domain from flagellin, leading to a decrease in the efficiency of flg22 epitope liberation. Consequently, defensive reactive oxygen species (ROS) production is delayed in sbt5.2 sbt1.7 double-mutant leaf disks compared to wild type following flagellin exposure.

Introduction We report a case of megaureter in a functional solitary kidney in which surgery was performed after bladder capacity was increased by home bladder cycling. Case presentation A 6‐day‐old girl with a left megaureter, a right multicystic dysplastic kidney, and bladder hypoplasia underwent percutaneous left nephrostomy for obstructive renal failure. At 8 months, home bladder cycling was initiated to increase bladder capacity before the planned ureterocystoneostomy. Surgery was performed after bladder capacity increased. The left ureter was compressed by the left umbilical ligament, so ureteral end‐to‐end anastomosis was performed at 1 year and 4 months. At 2 years and 8 months, cystometry showed age‐appropriate bladder capacity and improved bladder compliance. Conclusion To the best of our knowledge, this is the first report of bladder hypoplasia treated by home bladder cycling.

Abstract Coronary heart disease (CHD) risk is influenced by socioeconomic status-related parameters, particularly occupation. We investigated occupational gaps in CHD risk and how the introduction of remote work moderated the observed occupational differences in CHD risk during the coronavirus disease 2019 pandemic in Japan. Data from a web-based, nationwide cohort study, comprising 17,640 workers (aged 20–65 years) with baseline data from December 2020, were analyzed. Participants were grouped by occupation as upper-level nonmanual workers (managers/professionals) and others (reference group). The primary outcome was CHD (angina pectoris/myocardial infarction) onset retrospectively confirmed at the 1-year follow-up survey. Upper-level nonmanual workers exhibited a higher CHD incidence than others (2.3% vs. 1.7%). This association was pronounced in the younger (20–49 years) population, with a significant CHD risk (adjusted risk ratio = 1.88). Upper-level nonmanual workers exhibited nearly 15% higher remote work prevalence, with a significant remote work-related CHD risk (adjusted risk ratio = 1.92). The mediating effects of remote work explained an overall disparity of 32% among the younger population. Occupational gaps in CHD incidence in Japan differ from those in Western countries, where upper-level nonmanual workers have lower cardiovascular risk. In Japan, remote work can mediate CHD risk in the younger population of upper-level nonmanual workers.

Abstract Ehlers–Danlos syndrome spondylodysplastic type 3 (EDSSPD3, OMIM 612350) is an inherited recessive connective tissue disorder that is caused by loss of function of SLC39A13/ZIP13, a zinc transporter belonging to the Slc39a/ZIP family. We previously reported that patients with EDSSPD3 harboring a homozygous loss of function mutation (c.221G > A, p.G64D) in ZIP13 exon 2 (ZIP13 G64D ) suffer from impaired development of bone and connective tissues, and muscular hypotonia. However, whether ZIP13 participates in the early differentiation of these cell types remains unclear. In the present study, we investigated the role of ZIP13 in myogenic differentiation using a murine myoblast cell line (C2C12) as well as patient-derived induced pluripotent stem cells (iPSCs). We found that ZIP13 gene expression was upregulated by myogenic stimulation in C2C12 cells, and its knockdown disrupted myotubular differentiation. Myocytes differentiated from iPSCs derived from patients with EDSSPD3 (EDSSPD3-iPSCs) also exhibited incomplete myogenic differentiation. Such phenotypic abnormalities of EDSSPD3-iPSC-derived myocytes were corrected by genomic editing of the pathogenic ZIP13 G64D mutation. Collectively, our findings suggest the possible involvement of ZIP13 in myogenic differentiation, and that EDSSPD3-iPSCs established herein may be a promising tool to study the molecular basis underlying the clinical features caused by loss of ZIP13 function.

Background: Group B Streptococci (GBS) are common vaginal bacteria found in 20–30% of pregnant women and a significant cause of invasive infections in newborns. Recently, attention has been focused on the efficacy of probiotics during the perinatal period. However, the effect of probiotic intake on the mother-to-child transmission (MTCT) of GBS remains unknown. Methods: Pregnant women with positive GBS results from vaginal and rectal swab cultures at 35–37 weeks of gestation were randomly assigned to the probiotic group or the control group in an open-label manner at the Department of Obstetrics and Gynecology, San-ikukai Hospital, Tokyo, Japan. The probiotic group received Lactobacillus reuteri during antenatal checkups from 35 to 37-week gestation to 1 month after delivery. Rectal swabs were obtained from the newborns at 5 days and at 1 month of age. Whole-genome sequencing was performed to test for GBS strains in the mother, whose newborn carried GBS at the 1-month checkup. Multi-locus sequence typing and single nucleotide polymorphism analyses were performed to identify MTCT. Results: Overall, 67 mother-infant pairs were included, with 31 in the probiotic group and 36 in the control group. The positivity rate of GBS in newborns at 1 month of age was 10% (n = 3) in the probiotic group and 28% (n = 10) in the control group. In newborns carrying GBS at 1 month of age, genetic analysis revealed that the MTCT rate was 6% in the probiotic group and 22% in the control group, although the difference was not statistically significant (p = 0.0927). Conclusion: No statistically significant difference was found; however, the consumption of L. reuteri by women with GBS-positive pregnancies may inhibit the MTCT of GBS.

Abstract This study aimed to evaluate the prognostic impact and predictors of persistent renal dysfunction in acute kidney injury (AKI) after an emergency percutaneous coronary intervention (PCI) for acute myocardial infarction (AMI). A total of 877 patients who underwent emergency PCI for AMI were examined. AKI was defined as serum creatinine (SCr) ≥ 0.3 mg/dL or ≥ 50% from baseline within 48 h after PCI. Persistent AKI was defined as residual impairment of SCr ≥ 0.3 mg/dL or ≥ 50% from baseline 1 month after the procedure. The primary outcome was the composite endpoints of death, myocardial infarction, hospitalization for heart failure, stroke, and dialysis. AKI and persistent AKI were observed in 82 (9.4%) and 25 (2.9%) patients, respectively. Multivariate Cox proportional hazards analysis demonstrated that persistent AKI, but not transient AKI, was an independent predictor of primary outcome (hazard ratio, 4.99; 95% confidence interval, 2.30–10.8; P 75 years, left ventricular ejection fraction

Background Acute kidney injury (AKI) is a prevalent complication in critically ill patients that affects the timing of renal replacement therapy (RRT) initiation. This study aimed to develop and validate the SACrA score for predicting non-emergent initiations (BUN ≥112 mg/dL or oliguria for >72 h) of RRT in critically ill patients.Methods We conducted a retrospective cohort study using data from two cohorts. The derivation cohort included patients admitted to the ICU between November 2021 and December 2023, whereas the validation cohort included patients admitted between September 2019 and October 2021. The primary outcome was non-emergent RRT initiation. The multivariate logistic regression with stepwise selection based on the Akaike information criterion finalized the model, including the variables, such as sex, albumin (Alb), creatinine (Cr), and APACHE II score (SACrA).Results The derivation and validation cohorts comprised 470 and 476 patients, respectively. The SACrA score showed a strong predictive performance for non-emergent RRT initiation in both the cohorts. Cohort 1 had an ROC–AUC of 0.971, with a calibration slope of 0.982 and an intercept of 0.009, whereas cohort 2 had an ROC–AUC of 0.918, with a calibration slope of 0.988 and an intercept of 0.004.Conclusions The SACrA score is a robust tool for predicting non-emergent RRT initiation in critically ill patients using readily available clinical variables. Though additional data are needed to validate the SACrA score, our analysis suggests the tool may help clinicians make informed decisions, reduce unnecessary RRT, and thereby improve patient outcomes.

TCRαβ+ CD4− CD8− double-negative T (DNT) cells are minor populations in peripheral blood, and their roles have mostly been discussed in inflammation and autoimmunity. However, the functions of DNT cells in tumor microenvironment remain to be elucidated. We investigated their characteristics, possible origins and functions in colorectal cancer tissues as well as their corresponding tumor-draining lymph nodes. We found a significant enrichment of DNT cells in tumor tissues compared with their corresponding lymph nodes, especially in tumors with lower T cell infiltration. T cell receptor (TCR) sequence analysis of CD4+ T, CD8+ T and DNT cells indicated that TCR sequences detected in DNT cells were found in CD8+ T cells, but rarely in CD4+ T cells, suggesting that a part of DNT cells was likely to be originated from CD8+ T cells. Through a single-cell transcriptomic analysis of DNT cells, we found that a DNT cell cluster, which showed similar phenotypes to central memory CD8+ T cells with low expression of effector and exhaustion markers, revealed some specific gene expression patterns, including higher GZMK expression. Moreover, in flow cytometry analysis, we found that DNT cells lost production of cytotoxic mediators. These findings imply that DNT cells might function as negative regulators of anti-tumor immune responses in tumor microenvironment.

AbstractIntravascular large B-cell lymphoma (IVLBCL) is a rare subtype of malignant lymphoma (ML). Here, we present a case of IVLBCL initially suspected as invasive fungal rhinosinusitis (IFRS). A 64-year-old woman was referred to our hospital due to persistent fever, headache, and rhinorrhea. After admission, her overall condition rapidly deteriorated, leading to a diagnosis of septic shock. Blood examination revealed elevated serum lactate dehydrogenase and soluble interleukin 2 receptor levels suggestive of ML. Computed tomography revealed a high-density area with calcifications within the sinus cavity. Although IFRS was the primary suspicion, subsequent endoscopic sinus surgery disconfirmed this hypothesis based on histological findings. Unfortunately, the patient succumbed to multiple organ failure 12 days after admission, with an autopsy confirming IVLBCL. It is crucial to consider IVLBCL as a potential differential diagnosis in cases involving fever of unknown origin and progressive deterioration of the general condition.

Abstract Background and Aim Increased liver fibrosis scores (LFS), such as fibrosis‐4 index (FIB‐4) or non‐alcoholic fatty liver disease fibrosis score (NFS), and fatty liver are known risk factors for severe coronavirus disease 2019 (COVID‐19). The purpose of this study was to identify the best scores, which predict the prognosis of COVID‐19. Methods Participants comprised consecutive Japanese COVID‐19 patients admitted to our hospital between February 14, 2020, and April 14, 2021. Multivariate logistic regression analysis was performed to evaluate the relationships between LFS (FIB‐4, NFS, aspartate aminotransferase‐to‐platelet ratio index [APRI], BARD score, and hepatic steatosis index [HSI]) or fatty liver on computed tomography (CT), and severity of COVID‐19. Results Of the 415 patients (mean age, 59 years), 177 patients (42.7%) needed oxygen therapy, 90 patients (21.7%) worsened to severe COVID‐19, and 45 patients (10.8%) died during admission. Multivariate logistic regression analysis showed that increased FIB‐4 and NFS were risk factors for death, severe COVID‐19, and oxygen demand; that increased BARD was a risk factor for severe COVID‐19 and oxygen demand; and that increased APRI and HSI were not risk factors for any status of COVID‐19. Furthermore, increased NFS or BARD and fatty liver were independent risk factors for severe COVID‐19 and oxygen demand. Conclusions This study showed that FIB‐4 and NFS were the best liver fibrosis scores that predicted worse prognosis for COVID‐19, and that increased NFS or BARD and fatty liver evident on CT represented independent risk factors for severe COVID‐19 and oxygen demand.

Sesame (Sesamum indicum) is an oilseed crop which is increasingly recognised as a functional food by consumers due to its nutritional and nutraceutical components. Consequently, global demand for sesame has increased significantly over the last three decades. Sesame is an important export crop in producing countries, contributing to their socio-economic development. However, in recent years, major foodborne incidents have been associated with imported sesame seeds and products made with these seeds. Foodborne hazards are a potential risk to consumer health and hinder international trade due to border rejections and increased import controls. An insight into the routes of contamination of these hazards across the value chain and factors affecting persistence may lead to more focused intervention and prevention strategies. It was observed that Salmonella is a significant microbial hazard in imported sesame seeds and has been associated with several global outbreaks. Sesame is mainly cultivated in the tropical and subtropical regions of Africa and Asia by smallholder farmers. Agricultural and manufacturing practices during harvesting, storage, and processing before export may allow for the contamination of sesame seeds with Salmonella. However, only a few studies collect data on the microbiological quality of sesame across the value chain in producing countries. In addition, the presence of mycotoxins and pesticides above regulatory limits in sesame seeds is a growing concern. Eliminating foodborne hazards in the sesame value chain requires urgent attention from researchers, producers, processors, and regulators and suggestions for improving the safety of these foods are discussed.

Abstract Foraging plays a vital role in the survival of wildlife, and shifts in food availability can impact species fitness and survival. Ursids are known to consume a wide variety of foods and are known to be opportunistic omnivores. Consequently, seasonal shifts in diet, which correspond to temporal and spatial shifts in the availability of food resources, have long captivated researchers studying the foraging behavior of Ursidae. Nevertheless, comprehensive dietary studies encompassing both the population and individual levels remain scarce. In this study, we investigated the dietary patterns of Asiatic black bears (Ursus thibetanus) at both the population and individual levels, using data collected through GPS collars and field surveys of individual bear scat samples in Nagano Prefecture, Japan, from 2016 to 2020. From early April to late June, bears mainly foraged on green vegetation. During this period, male and large‐bodied female bears showed a strong preference for green vegetation. Small‐bodied female bears also ate mostly green vegetation but tended to consume more fruit than other bears towards the end of this period. From June to October, bears' diets included a substantial amount of fruit, with notable peaks in fruit consumption in late June and early September. During the summer months, female bears often incorporated social insects into their diet compared to the population‐level trend. In mid‐September, the consumption of seeds from the Fagaceae family surged, becoming the primary dietary component during this period. This trend was consistently observed across the population. These findings underscore the importance conducting in‐depth dietary analyses that take into account individual characteristics such as sex, age, and body weight.

IntroductionCampylobacter spp. are a public health concern, yet there is still no effective vaccine or medicine available.MethodsHere, we developed a Campylobacter jejuni-specific antibody and found that it targeted a menaquinol cytochrome c reductase complex QcrC.ResultsThe antibody was specifically reactive to multiple C. jejuni strains including clinical isolates from patients with acute enteritis and was found to inhibit the energy metabolism and growth of C. jejuni. Different culture conditions produced different expression levels of QcrC in C. jejuni, and these levels were closely related not only to the energy metabolism of C. jejuni but also its pathogenicity. Furthermore, immunization of mice with recombinant QcrC induced protective immunity against C. jejuni infection.DiscussionTaken together, our present findings highlight a possible antibody- or vaccination-based strategy to prevent or control Campylobacter infection by targeting the QcrC-mediated metabolic pathway.

IntroductionThe conventional method of placing transcranial direct current stimulation (tDCS) electrodes is just above the target brain area. However, this strategy for electrode placement often fails to improve motor function and modulate cortical excitability. We investigated the effects of optimized electrode placement to induce maximum electrical fields in the leg regions of both M1 and SMA, estimated by electric field simulations in the T1and T2-weighted MRI-based anatomical models, on motor performance and cortical excitability in healthy individuals.MethodsA total of 36 healthy volunteers participated in this randomized, triple-blind, sham-controlled experiment. They were stratified by sex and were randomly assigned to one of three groups according to the stimulation paradigm, including tDCS with (1) anodal and cathodal electrodes positioned over FCz and POz, respectively, (A-P tDCS), (2) anodal and cathodal electrodes positioned over POz and FCz, respectively, (P-A tDCS), and (3) sham tDCS. The sit-to-stand training following tDCS (2 mA, 10 min) was conducted every 3 or 4 days over 3 weeks (5 sessions total).ResultsCompared to sham tDCS, A-P tDCS led to significant increases in the number of sit-to-stands after 3 weeks training, whereas P-A tDCS significantly increased knee flexor peak torques after 3 weeks training, and decreased short-interval intracortical inhibition (SICI) immediately after the first session of training and maintained it post-training.DiscussionThese results suggest that optimized electrode placement of the maximal EF estimated by electric field simulation enhances motor performance and modulates cortical excitability depending on the direction of current flow.

Polycystic ovary syndrome (PCOS) is associated with an increased risk of psychological distress as well as enhanced responses to psychosocial stress. Recently, it was hypothesized that PCOS patients may be at high risk of novel COVID-19 infections and worse clinical presentations during such infections. Here, we evaluated the effects of PCOS on stress responses to bacterial and viral mimetics using dihydrotestosterone-induced PCOS model rats. Lipopolysaccharide (LPS; a bacterial mimetic) or polyinosinic-polycytidylic acid (Poly-IC; a viral mimetic) was injected into PCOS model rats (PCOS) and non-PCOS rats (control), and the rats' stress responses were evaluated. In the PCOS group, the rats’ anorectic and febrile responses to LPS injection were enhanced, whereas their anorectic and febrile responses to Poly-IC injection were unaltered. The PCOS group also exhibited greater changes in peripheral cytokine levels in response to LPS, but not Poly-IC. On the contrary, after the injection of Poly-IC depressed locomotor activity was more evident in the PCOS group, whereas no such changes were observed after LPS injection. These findings indicate that although the stress responses of PCOS model rats to infection may be enhanced, the patterns of change in stress responses and their underlying mechanisms may differ between bacterial and viral infections.

Recent studies have highlighted the indispensable role of oxidized lipids in inflammatory responses, cell death, and disease pathogenesis. Consequently, inhibitors targeting oxidized lipids, particularly lipid-derived radicals critical in lipid peroxidation, which are known as radical-trapping antioxidants (RTAs), have been actively pursued. We focused our investigation on nitroxide compounds that have rapid second-order reaction rate constants for reaction with lipid-derived radicals. A novel screening system was developed by employing competitive reactions between library compounds and a newly developed profluorescence nitroxide probe with lipid-derived radicals to identify RTA compounds. A PubMed search of the top hit compounds revealed their wide application as repositioned drugs. Notably, the inhibitory efficacy of methyldopa, selected from these compounds, against retinal damage and bilateral common carotid artery stenosis was confirmed in animal models. These findings underscore the efficacy of our screening system and suggest that it is an effective approach for the discovery of RTA compounds.

Abstract A 69‐year‐old ex‐smoker Japanese man presented with a left mediastinal lymph node and left upper lobe tumour. Bronchoscopic biopsy specimens from the enlarged left mediastinal lymph node and left upper lobe tumour revealed small cell lung carcinoma (SCLC). He was treated with first‐line chemotherapy with carboplatin, etoposide, and atezolizumab for four courses and subsequent atezolizumab maintenance therapy. However, his left upper lobe lung tumour only increased in size, and left upper lobectomy revealed combined SCLC (adenocarcinoma and chondrosarcoma‐like features). Four months after lobectomy, liver metastasis of chondrosarcoma‐like features (similar to pathological findings of the left upper lobe tumour) were observed. Combined SCLC, including sarcomatous components, is rare and poorly responds to chemotherapy. The metastases of combined SCLC in this patient were of only one type of histological component, making diagnosis and treatment difficult. If treatment for SCLC responds inadequately, considering combined SCLC and actively re‐examining histological diagnosis is necessary.

How the microbiome regulates responses of systemic innate immune cells is unclear. In the present study, our purpose was to document a novel mechanism by which the microbiome mediates crosstalk with the systemic innate immune system. We have identified a family of microbiome Bacteroidota-derived lipopeptides—the serine-glycine (S/G) lipids, which are TLR2 ligands, access the systemic circulation, and regulate proinflammatory responses of splenic monocytes. To document the role of these lipids in regulating systemic immunity, we used oral gavage with an antibiotic to decrease the production of these lipids and administered exogenously purified lipids to increase the systemic level of these lipids. We found that decreasing systemic S/G lipids by decreasing microbiome Bacteroidota significantly enhanced splenic monocyte proinflammatory responses. Replenishing systemic levels of S/G lipids via exogenous administration returned splenic monocyte responses to control levels. Transcriptomic analysis demonstrated that S/G lipids regulate monocyte proinflammatory responses at the level of gene expression of a small set of upstream inhibitors of TLR and NF-κB pathways that include Trem2 and Irf4. Consistent with enhancement in proinflammatory cytokine responses, decreasing S/G lipids lowered gene expression of specific pathway inhibitors. Replenishing S/G lipids normalized gene expression of these inhibitors. In conclusion, our results suggest that microbiome-derived S/G lipids normally establish a level of buffered signaling activation necessary for well-regulated innate immune responses in systemic monocytes. By regulating gene expression of inflammatory pathway inhibitors such as Trem2, S/G lipids merit broader investigation into the potential dysfunction of other innate immune cells, such as microglia, in diseases such as Alzheimer’s disease.