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COVID-19 has spread worldwide since December 2019. Among the mutated variants, some were designated by the World Health Organization as variants of concern because of their transmissibility or virulence (1). [...]

Background: We investigated the efficacy and safety of dupilumab in Japanese patients aged ≥6 months to

Abstract Primates must adapt to changing environments by optimizing their behavior to make beneficial choices. At the core of adaptive behavior is the orbitofrontal cortex (OFC) of the brain, which updates choice value through direct experience or knowledge-based inference. Here, we identify distinct neural circuitry underlying these two separate abilities. We designed two behavioral tasks in which two male macaque monkeys updated the values of certain items, either by directly experiencing changes in stimulus-reward associations, or by inferring the value of unexperienced items based on the task’s rules. Chemogenetic silencing of bilateral OFC combined with mathematical model-fitting analysis revealed that monkey OFC is involved in updating item value based on both experience and inference. In vivo imaging of chemogenetic receptors by positron emission tomography allowed us to map projections from the OFC to the rostromedial caudate nucleus (rmCD) and the medial part of the mediodorsal thalamus (MDm). Chemogenetic silencing of the OFC-rmCD pathway impaired experience-based value updating, while silencing the OFC-MDm pathway impaired inference-based value updating. Our results thus demonstrate dissociable contributions of distinct OFC projections to different behavioral strategies, and provide new insights into the neural basis of value-based adaptive decision-making in primates.

To determine the characteristics of pediatric patients 0–19 years of age who died after onset of SARS-CoV-2 infection in Japan during January 1–September 30, 2022, we reviewed multiple sources. We identified 62 cases, collected detailed information from medical records and death certificates, and conducted interviews, resulting in 53 patients with detailed information for our study. Among 46 patients with internal causes of death (i.e., not external causes such as trauma), 15% were

Abstract Background In patients with conjoined nerve roots, hemilaminectomy with sufficient exposure of the intervertebral foramen or lateral recess is required to prevent destabilization and ensure correct mobility of the lumbosacral spine. To the best of our knowledge, no case reports have detailed the long-term course of conjoined nerve roots after surgery. Case presentation We report the case of a 51-year-old Japanese man with a conjoined nerve root. The main symptoms were acute low back pain, radiating pain, and right leg muscle weakness. Partial laminectomy was performed with adequate exposure to the conjoined nerve root. The symptoms completely resolved immediately after surgery. However, the same symptoms recurred 7 years postoperatively. The nerve root was compressed because of foraminal stenosis resulting from L5–S disc degeneration. L5–S transforaminal lumbar interbody fusion was performed on the contralateral side because of an immobile conjoined nerve root. At 44 months after the second surgery, the patient had no low back pain or radiating pain, and the muscle weakness in the right leg had improved. Conclusions This is the first report of the long-term course of conjoined nerve root after partial laminectomy. When foraminal stenosis occurs after partial laminectomy, transforaminal lumbar interbody fusion from the contralateral side may be required because of an immobile conjoined nerve root.

Introduction This study intended to evaluate the medium-term effectiveness of a community-based medical education (CBME) program and to determine the program’s influence on the application rates of regional-quota students seeking to become residents in Tamba, Japan.Materials and Methods We conducted a cohort study of regional-quota students. Exposure factors included (1) experience compared to no experience of CBME in the Tamba area; (2) CBME experience compared to no experience in Tamba in the senior years (4–6 years of medical school) and experience in the junior years (1–3 years of medical school); and (3) experience in the senior years compared with those in the junior years. Outcome measures were applications to become a medical resident and actually becoming a medical resident at the Hyogo Prefectural Tamba Medical Center.Results Of 94 participants, 58 (61.7%) were male and 37 students (39.4%) had previous CBME experience in the Tamba area. In applying to become a resident at the Hyogo Prefectural Tamba Medical Center, students who had experienced CBME in the Tamba area in their senior years had significantly higher adjusted risk ratios compared to those who experienced it in their junior years. Regarding applications to become a resident, students who had experienced CBME in the Tamba area in their senior years had a significantly higher adjusted risk ratio than students who had not experienced CBME and students who had experienced CBME in their junior years.Conclusions There was a statistically significant application rate for residency programs among medical students who participated in the CBME program in their senior years compared with those who did not. This is the first study to confirm the medium-term effects of CBME after several years in short-term CBME programs of three days and two nights.

A 9-year-old boy was suspected of having acute myocardial infarction and emergency coronary angiogram was performed. No signs of flow limitation in either coronary artery was detected. We performed intravascular ultrasonography from the ascending aorta, which showed a ridge on the left main trunk acting like a valve, resulting in significant stenosis. Percutaneous coronary intervention with stent deployment was performed with good result.

Introduction: Concentrated growth factor (CGF) is a new-generation autologous platelet concentrate that promotes tissue regeneration and has anti-inflammatory properties. This randomized multicenter trial aimed to evaluate the effects of CGF on bone healing in combination with root-end microsurgery. Methods: Healthy adult patients indicated for root-end microsurgery were randomly assigned to either the CGF or control (no CGF implantation) groups. CGF was implanted into the bone cavity after root-end filling with mineral trioxide aggregate. Clinical and periapical radiographic evaluations were conducted at 1, 3, 6, and 12 months postoperatively, with follow-up cone-beam computed tomography (CBCT) at 6 months. The lesion volume reduction rate was calculated based on data from the preoperative and follow-up CBCT images. Results: A total of 24 patients were enrolled. The treatment success rate was 91.7% and 83.3% on 12-month periapical radiography and 6-month CBCT, respectively, without a significant difference between the two groups. The lesion volume reduction rate in the CGF group (75.6%) was significantly higher than that in the control (61.0%) group. Conclusions: Autologous CGF in conjunction with root-end microsurgery accelerated lesion reduction as observed on CBCT. Administering autologous blood products to stimulate healing in addition to removing the source of infection appears to be a promising treatment option for root-end microsurgery.

BackgroundIncreased levels of plasminogen activator inhibitor-1 (PAI-1) in tumors have been found to correlate with poor clinical outcomes in patients with cancer. Although abundant data support the involvement of PAI-1 in cancer progression, whether PAI-1 contributes to tumor immune surveillance remains unclear. The purposes of this study are to determine whether PAI-1 regulates the expression of immune checkpoint molecules to suppresses the immune response to cancer and demonstrate the potential of PAI-1 inhibition for cancer therapy.MethodsThe effects of PAI-1 on the expression of the immune checkpoint molecule programmed cell death ligand 1 (PD-L1) were investigated in several human and murine tumor cell lines. In addition, we generated tumor-bearing mice and evaluated the effects of a PAI-1 inhibitor on tumor progression or on the tumor infiltration of cells involved in tumor immunity either alone or in combination with immune checkpoint inhibitors.ResultsPAI-1 induces PD-L1 expression through the JAK/STAT signaling pathway in several types of tumor cells and surrounding cells. Blockade of PAI-1 impedes PD-L1 induction in tumor cells, significantly reducing the abundance of immunosuppressive cells at the tumor site and increasing cytotoxic T-cell infiltration, ultimately leading to tumor regression. The anti-tumor effect elicited by the PAI-1 inhibitor is abolished in immunodeficient mice, suggesting that PAI-1 blockade induces tumor regression by stimulating the immune system. Moreover, combining a PAI-1 inhibitor with an immune checkpoint inhibitor significantly increases tumor regression.ConclusionsPAI-1 protects tumors from immune surveillance by increasing PD-L1 expression; hence, therapeutic PAI-1 blockade may prove valuable in treating malignant tumors.

Abstract Objective To examine the significant events experienced by initial trainees during community medicine training, evaluate their impact on community medicine practice, and support improvements in rural community medicine training. Results Three faculty teachers independently evaluated the reports of 25 residents who had completed a four-week community medicine training in a rural area to analyze major events. The reports were analyzed using topics from the Model Core Curriculum for Medical Education that relate to rural medicine. The most frequently reported items were identified as follows: Primary care: 9 (36.0%); integrated community care systems: 8 (32.0%); medical care in the local community: 7 (28.0%); home health care and systems, patient-physician relationship, and end-of-life medical treatment and care: 6 each (24.0%). Reports from residents describing events related to home health care and systems and end-of-life medical treatment and care were related to more than one item.

Study Design Retrospective study. Purpose This research aimed to assess the clinical outcomes of patients with traumatic cervical spine dislocation who underwent closed reduction employing our approach. Overview of Literature Bedside closed reduction is the quickest procedure for repairing traumatic cervical spine dislocations; nevertheless, it also possesses the risk of neurological deterioration. Methods For closed reduction, the patient’s head was elevated on a motorized bed, the cervical spine was placed at the midline, traction of 10 kg was applied, the motorized bed was gradually returned to a flat position, the head was lifted off the bed, and the cervical spine was slowly adjusted to a flexed position. The weight of traction was elevated by 5-kg increments until the positional shift was attained. Subsequently, the bed was gradually tilted while traction was applied again to return the cervical spine to the midline position. Results Of the 43 cases of cervical spine dislocation, closed reduction was carried out in 40 cases, of which 36 were successful. During repositioning, three patients experienced a temporary worsening of their neck pain and neurological symptoms that enhanced when the cervical spine was flexed. Closed reduction was conducted while the patient was awake; nevertheless, sedation was needed in three cases. Among the 24 patients whose pretreatment paralysis had been characterized by American Spinal Injury Association Impairment Scale (AIS) grades A–C, seven patients (29.2%) demonstrated an enhancement of two or more AIS grades at the last observation. Conclusions Our closed reduction approach safely repaired traumatic cervical spine dislocations.

Abstract Background Adult spinal deformity has a substantially debilitating effect on older people’s physical and mental health. However, the impact of sagittal malalignment on locomotive syndrome (LS), sarcopenia, and physical function in community-dwelling older women has not yet been clarified. This study aimed to investigate the association between these factors in community-dwelling middle aged and older women. Methods A total of 361 women were recruited from participants performing aquatic exercises in a rural area of Japan. The body mass index, skeletal muscle mass index, trunk muscle mass, spinal inclination angle (SIA), grip strength, timed up-and-go test (TUG), maximum stride of the participants, and one-leg standing time were measured. Low back pain (LBP)- and health-related quality of life (HRQOL) were evaluated using the Oswestry Disability Index (ODI) and the Short-Form 8 questionnaire. Associations between the global sagittal alignment using SIA and investigating parameters were analyzed. Results The prevalence of sarcopenia was 3.6%. The prevalence of LS (stages 1, 2, and 3) was 43.8% (158 of 361), and the number of participants in each LS stage was 203 (stage 0), 95 (stage 1), 28 (stage 2), and 35 (stage 3). The SIA was significantly correlated with the 25-question geriatric locomotive function scale (r′ = 0.292, p

Abstract Background Intrathecal baclofen therapy can substantially improve symptoms in most patients with severe spasticity due to traumatic spinal cord injury, multiple sclerosis, or cerebral paresis. To the best of our knowledge, decompression surgeries at the intrathecal catheter insertion site in patients with a preexisting intrathecal pump for drug delivery have not been reported. Case presentation We report the case of a 61-year-old Japanese man with lumbar spinal stenosis who underwent intrathecal baclofen therapy. We performed decompression for lumbar spinal stenosis at the intrathecal catheter insertion site during intrathecal baclofen therapy. The yellow ligament was removed by partial resection of the lamina under a microscope to avoid damage to the intrathecal catheter. The dura mater was distended. No obvious cerebrospinal fluid leakage was observed. Postoperatively, lumbar spinal stenosis symptoms improved, and spasticity remained well controlled with intrathecal baclofen therapy. Conclusions This is the first reported case of lumbar spinal stenosis decompression at an intrathecal catheter insertion site during intrathecal baclofen therapy. Preoperative preparation is necessary, as the intrathecal catheter may be replaced during surgery. We performed surgery without removing or replacing the intrathecal catheter, taking care not to damage the spinal cord by migrating the intrathecal catheter.

Abstract Background Flavanone 3-hydroxylase (F3H), a key enzyme in the flavonoid biosynthetic pathway, plays an important role in the regulation of flavonols and anthocyanidins accumulation. Citrus fruit is a rich source of flavonoids with varied flavonoid compositions among different varieties. To date, the study on F3H is limited in citrus, and its roles in regulating flavonoid accumulation in citrus fruit are still unclear. Results In this study, we isolated a CitF3H from three different citrus varieties, Satsuma mandarin (Citrus unshiu Marc.), Ponkan mandarin (C. reticulata Blanco) and blood orange ‘Moro’ (C. sinensis Osbeck). Functional analysis showed that CitF3H encoded a functional flavanone 3-hydroxylase. It catalyzed the hydroxylation of naringenin to yield dihydrokaempferol, which was a precursor of anthocyanins in flavonoid biosynthetic pathway. In the juice sacs, CitF3H was differentially expressed among the three citrus varieties, and its expression level was positively correlated with the accumulation of anthocyanins during the ripening process. In the juice sacs of Satsuma mandarin and Ponkan mandarin the expression of CitF3H kept constant at an extremely low level, and no anthocyanin was accumulated during the ripening process. In contrast, the expression of CitF3H increased rapidly along with the accumulation of anthocyanin in the juice sacs of blood orange ‘Moro’ during the ripening process. In addition, we found that blue light irradiation was effective to up-regulate the expression of CitF3H and improve anthocyanin accumulation in the juice sacs of blood orange ‘Moro’ in vitro. Conclusion CitF3H was a key gene regulating anthocyanin accumulation in the juice sacs of citrus fruit. The results presented in this study will contribute to elucidating anthocyanin biosynthesis in citrus fruit, and provide new strategies to improve the nutritional and commercial values of citrus fruit.

Abstract Although the identification of late adolescents with subthreshold depression (StD) may provide a basis for developing effective interventions that could lead to a reduction in the prevalence of StD and prevent the development of major depressive disorder, knowledge about the neural basis of StD remains limited. The purpose of this study was to develop a generalizable classifier for StD and to shed light on the underlying neural mechanisms of StD in late adolescents. Resting-state functional magnetic resonance imaging data of 91 individuals (30 StD subjects, 61 healthy controls) were included to build an StD classifier, and eight functional connections were selected by using the combination of two machine learning algorithms. We applied this biomarker to an independent cohort (n = 43) and confirmed that it showed generalization performance (area under the curve = 0.84/0.75 for the training/test datasets). Moreover, the most important functional connection was between the left and right pallidum, which may be related to clinically important dysfunctions in subjects with StD such as anhedonia and hyposensitivity to rewards. Investigation of whether modulation of the identified functional connections can be an effective treatment for StD may be an important topic of future research.

Abstract Background There is increasing evidence that diagnostic salivary tests measuring inflammatory biomarkers are being developed to assess inflammatory status for early detection, prevention, and progression of periodontal disease. Therefore, the aim of the present study was to investigate and identify the salivary biomarker that can predict the inflammatory status of periodontal disease. Methods A total of 36 patients (28 women and 8 men) with an average age of 57 years were investigated. Unstimulated saliva was collected from the recruited subjects and analyzed using SillHa, a saliva-testing device that measures bacteria count, saliva buffer capacity, acidity, leukocyte esterase, protein, and ammonia. Periodontal parameters were then obtained by clinical examination and initial periodontal therapy was performed. Data obtained with SillHa were compared with clinical periodontal parameters at baseline, re-examination (three months from baseline), and final examination (six months from re-examination). Results Leukocyte esterase activity in saliva measured by SillHa; BOP and PCR measured by clinical examination showed a significant difference between baseline and final examination and between re-examination and final examination. Patients in the lower median group (group 1) had a significant difference in leukocyte esterase activity between baseline and final examination and re-examination and final examination. In addition, patients in Group 1 had significantly lower BOP between baseline and final examination. While patients in the higher median group (group 2) showed a modest decrease in leukocyte esterase activity, which was significant only between baseline and final examination, no significant changes were observed concerning BOP. Furthermore, the associated systemic disease was observed in 30% and 81.2% of group 1 and 2 patients, respectively. Conclusion The results suggest that leukocyte esterase activity in saliva measured by SillHa could serve as a reliable diagnostic marker for monitoring inflammatory status in periodontal disease.

Our current examples of transportation needs assessments focus on existing and established travel behaviors to predict the needs of a community, but there are populations that face additional burdens that are not captured outside of surveys and data collection efforts in academia. The goal of this research is to identify the best practices to collect data on the unmet travel needs of a neighborhood, particularly for disadvantaged populations. This project is a mixed-methods approach involving a literature review, open-ended interviews with academics and professionals with survey experience, and focus groups with community members in Downtown Huntington Park. This study finds that the ideal approach for collecting information on the travel needs of a neighborhood combines the benefits of active and passive data collection using smartphone-based surveys and thorough outreach to ensure that the survey instrument works for underrepresented populations. The current efforts to study the travel needs of disadvantaged populations in studies occur at a smaller scale, but with a focused effort in relationship building and community context. There are quality resources, examples, and guides for community needs assessments that can serve as a template for agencies seeking to explore the needs of their communities, such as the Mobility Equity Framework and the University of Kansas Community Tool Box. Community members in Downtown Huntington Park conveyed a willingness to participate in a smartphone-based travel survey, expressed their car-dependent nature, and provided valuable feedback on how outreach could be conducted in their neighborhood.

Our current examples of transportation needs assessments focus on existing and established travel behaviors to predict the needs of a community, but there are populations that face additional burdens that are not captured outside of surveys and data collection efforts in academia. The goal of this research is to identify the best practices to collect data on the unmet travel needs of a neighborhood, particularly for disadvantaged populations. This project is a mixed-methods approach involving a literature review, open-ended interviews with academics and professionals with survey experience, and focus groups with community members in Downtown Huntington Park. This study finds that the ideal approach for collecting information on the travel needs of a neighborhood combines the benefits of active and passive data collection using smartphone-based surveys and thorough outreach to ensure that the survey instrument works for underrepresented populations. The current efforts to study the travel needs of disadvantaged populations in studies occur at a smaller scale, but with a focused effort in relationship building and community context. There are quality resources, examples, and guides for community needs assessments that can serve as a template for agencies seeking to explore the needs of their communities, such as the Mobility Equity Framework and the University of Kansas Community Tool Box. Community members in Downtown Huntington Park conveyed a willingness to participate in a smartphone-based travel survey, expressed their car-dependent nature, and provided valuable feedback on how outreach could be conducted in their neighborhood.