An approach for the analysis of axonal neuroinflammation by measuring dual biomarkers of oligodendrocytes and inflammatory cytokine in human plasma.

The myelin sheath surrounding axons is vulnerable to mechanical stresses after head injuries, as well as autoimmune attacks and degeneration in neurological disorders. Unfortunately, there is currently no effective method to assess these axonal conditions in individual patients. We have developed a sandwich immunoassay detecting dual signals of myelin oligodendrocyte glycoprotein (MOG) and interleukin 1B (IL1B) in human plasma ([IL1B on MOG]). While IL1B is one of common inflammation markers, its lack of tissue specificity is addressed by identifying IL1B on extracellular vesicles from oligodendrocytes isolated using anti-MOG, suggesting inflammation around axons. In 77 control subjects, plasma levels of [IL1B on MOG] did not increase more than 2 fold from baseline. During the sports season, 14% (151 football players) and 22% (18 rugby players) exhibited a substantial 2-17 fold increase, despite the absence of traumatic brain injuries. This elevation demonstrated a non-random pattern, with some individuals gradually rising towards the season's end, followed by a decline. [IL1B on MOG] levels also correlated with the clinical course of a post-concussion syndrome case. These data indicate that [IL1B on MOG] blood test is a potential marker for assessing mild axonal neuroinflammation.

The Effect of Prior Creatine Intake for 28 Days on Accelerated Recovery from Exercise-Induced Muscle Damage: A Double-Blind, Randomized, Placebo-Controlled Trial.

Despite the known beneficial effects of creatine in treating exercise-induced muscle damage (EIMD), its effectiveness remains unclear. This study investigates the recovery effect of creatine monohydrate (CrM) on EIMD. Twenty healthy men (21-36 years) were subjected to stratified, randomized, double-blind assignments. The creatine (CRE) and placebo (PLA) groups ingested creatine and crystalline cellulose, respectively, for 28 days. They subsequently performed dumbbell exercises while emphasizing eccentric contraction of the elbow flexors. The EIMD was evaluated before and after exercise. The range of motion was significantly higher in the CRE group than in the PLA group 24 h (h) post exercise. A similar difference was detected in maximum voluntary contraction at 0, 48, 96, and 168 h post exercise (p = 0.017-0.047). The upper arm circumference was significantly lower in the CRE group than in the PLA group at 48, 72, 96, and 168 h post exercise (p = 0.002-0.030). Similar variation was observed in the shear modulus of the biceps brachii muscle at 96 and 168 h post exercise (p = 0.003-0.021) and in muscle fatigue at 0 and 168 h post exercise (p = 0.012-0.032). These findings demonstrate CrM-mediated accelerated recovery from EIMD, suggesting that CrM is an effective supplement for EIMD recovery.

Effects of human herpesvirus 6B reactivation on cognitive function in cord blood transplant recipients: a prospective multicenter study.

This prospective multicenter study aimed to determine the effects of human herpesvirus-6B (HHV-6B) reactivation on central nervous system (CNS) function in cord blood transplant (CBT) recipients. Our focus was to track HHV-6B reactivation and evaluate its association with delirium and cognitive function, specifically in the domains of verbal memory, attention/processing speed, and quality of life (QOL). A cohort of 38 patients participated in this study. Of the 37 patients evaluated, seven (18.9%) developed delirium, with six of these cases emerging after HHV-6B reactivation (median lag, 7 days). Evaluation of verbal memory showed that the final trial score for unrelated words at 70 days after transplantation was significantly lower than that before preconditioning (P = 0.004) among patients (n = 15) who experienced higher-level HHV-6B reactivation (median or higher maximum plasma HHV-6 DNA load for participating patients). Patients without higher-level reactivation did not show significant declines in verbal memory scores. QOL was assessed using the 36-item Short-Form Health Survey, and the social functioning score 1 year post-transplantation was significantly lower in patients who experienced higher-level HHV-6B reactivation than in those who did not. Our findings suggest that higher-level HHV-6B reactivation can detrimentally affect certain cognitive functions in CBT recipients.

Turning and sitting movements during timed up and go tests predict deterioration of physical function in middle-aged adults.

BACKGROUND: Deterioration of physical function in middle-aged adults is a significant challenge that can lead to increased risk of future falls. However, a screening method for the functional decline in middle-aged adults has not been established. RESEARCH QUESTION: To evaluate the relationship between biomechanical parameters assessed by the timed up and go test (TUG) and locomotive syndrome (LS) in middle-aged adults. METHODS: The inclusion criterion was: under 65 years of age. A total of 97 volunteers (mean age 51.1 years) participated in this study. An LS test was performed, including a 2-step test, a stand-up test, and a 25-question Geriatric Locomotive Function Scale. The TUG was measured using inertial measurement units (IMUs) at comfortable and fast speeds. We then determined the minimum values for anterior-posterior acceleration and angular velocity around the medial-lateral axis, as well as the maximum values of angular velocity around the vertical axis for the upper trunk and sacrum in a TUG phase. RESULTS: Angular velocity around the vertical axis for upper trunk and sacrum were significantly smaller in LS than non-LS in the turn phase of both speed conditions. For the fast speed condition, the minimum anterior-posterior acceleration for sacrum was greater in LS than in the non-LS condition for the stand-to-sit phase. Angular velocity around the vertical axis for turning and anterior-posterior acceleration from sitting were associated with detection of LS. SIGNIFICANCE: Turning and sitting movements during TUG should be observed using IMU to screen for physical function decline in middle aged adults.

Relationships between Changes in Muscle Shear Modulus, Urinary Titin N- Terminal Fragment, and Maximum Voluntary Contraction Torque after Eccentric Exercise of the Elbow Flexors.

The study aimed to investigate the relationships between the shear modulus of the biceps brachii (BB) and brachialis muscle (BA) and the total of the two (BB+BA), and urinary titin N-terminal fragment (UTF), maximum voluntary isometric contraction (MVC), and other indirect markers. Fifteen healthy men performed five sets of 10 eccentric contractions using a dumbbell corresponding to 50% of MVC at 90° measured at baseline. The elbow joint of the left arm was extended from 90° to 180° (180° = full extension) in 5 s in the exercise, and was returned with support from the examiner to prevent concentric contraction. Shear modulus of BB and BA were measured by ultrasound shear wave elastography, and UTF, MVC, and range of motion of the elbow joint (ROM) were recorded before; immediately after; and 1, 24, 48, 72, 96, and 168 h after the exercise. After calculating the shear modulus of BB and BA, two values were added (BB+BA). The shear modulus peaked at 48 h, UTF peaked at 96 h, MVC and ROM changed largest at immediately, and muscle soreness peaked at 48 h post-exercise. Significant (p < 0.05) relationships were found between changes in BB shear modulus and BA shear modulus (r = 0.874), BB+BA shear modulus (r = 0.977), UTF (r = 0.681), and MVC (r = -0.538). Significant (p < 0.05) relationships were also observed between changes in BA shear modulus and BB+BA shear modulus (r = 0.957), UTF (r = 0.682), MVC (r = -0.522), and ROM (r = -0.600). Moreover, significant (p < 0.05) relationships were observed between changes in BB+BA shear modulus and UTF (r = 0.703), MVC (r = -0.549), and ROM (r = -0.547). These results indicate that shear modulus of each muscle (i.e., BB and BA) provide more precise information about muscle damage than UTF, MVC and ROM.

Splenic sarcoid reaction mimicking metastases in patients after uterine cancer surgery: a report of two cases.

BACKGROUND: Tumor-associated sarcoid reactions have been observed with various tumors; however, they have not been reported with uterine cancer. We present two cases of splenic sarcoid reactions that mimicked metastases a few years after uterine cancer surgery. CASE PRESENTATION: Case 1 involved a 67-year-old female patient diagnosed with endometrial cancer (pT1aN0M0, pStage Ia, grade 1). The patient underwent open total abdominal hysterectomy and bilateral salpingo-oophorectomy with pelvic lymphadenectomy. Three years after the initial surgery, computed tomography (CT) and positron emission tomography CT showed multiple splenic masses with increasing numbers and sizes. Splenic metastases were diagnosed, and laparoscopic splenectomy was performed. The histopathological analysis revealed sarcoid reactions in the spleen. Case 2 involved a 47-year-old female patient diagnosed with endometrial cancer (pT1aN0M0, pStage Ia, grade 1). The patient underwent laparoscopic total abdominal hysterectomy and bilateral salpingo-oophorectomy with pelvic lymphadenectomy. Two years after the initial surgery, multiple splenic masses were observed. We performed laparoscopic splenectomy for the splenic metastases. Granuloma formations were identified in the splenic specimen and perisplenic lymph nodes that were removed simultaneously, resulting in a final diagnosis of sarcoid reaction. A review of the lymph nodes at the time of the previous uterine surgery revealed granuloma formation. Other than the presence of splenic masses, no findings suggestive of recurrence were observed in these cases. Uterine cancer and sarcoid reactions progressed without recurrence after splenectomy. CONCLUSIONS: To the best of our knowledge, this is the first report of the late development of splenic sarcoid reactions after uterine cancer surgery. Sarcoid reactions and metastases are difficult to diagnose based on preoperative imaging results. However, reviewing the specimen at the time of the initial resection, the number of lesions, and the clinical findings (other than imaging findings) may aid in the determination of the correct diagnosis.

Prognostic Value of Peritoneal Lavage Cytology in Potentially Resectable Pancreatic Cancer Stratified by Cytologic Status.

BACKGROUND/AIM: Patients with pancreatic ductal adenocarcinoma (PDAC) with positive peritoneal lavage cytology (CY) reportedly have poor prognoses. However, the value of diagnosis of suspicious for malignancy on CY is unknown. This study aimed to elucidate the prognostic impact of CY by focusing on CY subgroups. PATIENTS AND METHODS: Data were collected from 231 resectable PDAC patients who underwent curative-intent resection. Patients were divided into three CY-based groups: negative (CY0), suspicious for malignancy (CY-S), and positive (CY1). Clinicopathological characteristics and prognostic factors were analyzed. RESULTS: CY1 and CY-S were diagnosed in 7.8% and 3.9% of the patients, respectively. The CY1 group had significantly larger tumors and higher frequencies of distal tumors, anterior pancreatic tissue invasion, retropancreatic tissue invasion, and R1 resection than the CY0 group. Patient characteristics did not differ between the CY0 and CY-S groups. The CY1 group exhibited worse survival than the CY0 and CY-S groups (median survival time: 18.8 vs. 39.6 months, p=0.0021 and vs. 62.2 months, p=0.018). Multivariate analysis for survival indicated that a tumor size >2 cm, preoperative CA19-9 value >100 U/ml, CY1, lymph node metastasis, R1 resection, and lack of adjuvant chemotherapy were associated with poor prognosis. Both the CY1 and CY-S groups had higher frequencies of peritoneal recurrence than the CY0 group (50% vs. 11.8%, p<0.001 and 44.4% vs. 11.8%, p=0.019). CONCLUSION: The prognosis of the CY1 group was poor. Although CY-S was associated with a higher frequency of peritoneal recurrence than CY0, the long-term outcomes of patients with surgical treatment were acceptable.

Safety and efficacy of post-haematopoietic cell transplantation maintenance therapy with blinatumomab for relapsed/refractory CD19-positive B-cell acute lymphoblastic leukaemia: protocol for a phase I-II, multicentre, non-blinded, non-controlled trial (JPLSG SCT-ALL-BLIN21).

INTRODUCTION: Relapsed and refractory B-cell acute lymphoblastic leukaemia (R/R-B-ALL) is linked to a significant relapse rate after allogeneic haematopoietic cell transplantation (allo-HCT) in children, adolescents and young adults (CAYA). No standard treatment has been established to prevent relapse after allo-HCT for R/R-B-ALL, which is an unmet medical need. The administration of blinatumomab after allo-HCT is expected to enhance the antileukaemic effect on residual CD19-positive blasts by donor-derived CD3-positive T-cells. METHODS AND ANALYSIS: The goal of this multicentre, open-label, uncontrolled, phase I-II clinical trial is to assess the safety and effectiveness of post-transplant maintenance therapy with blinatumomab for CAYA patients (25 years old or younger) with CD19-positive R/R-B-ALL who have received allo-HCT beyond first complete remission (CR) and have CR with haematological recovery between 30 and 100 days after allo-HCT. Eighty-five paediatric institutions in Japan are participating in this study. Forty-one patients will enrol within 2.25-year enrolment period and follow-up period is 1 year. The primary endpoints are the treatment completion rate for phase I study and the 1-year graft-versus-host disease-free/relapse-free survival rate for phase II study, respectively. ETHICS AND DISSEMINATION: This research was approved by the Central Review Board at National Hospital Organization Nagoya Medical Center (Nagoya, Japan) on 21 January 2022 and was registered at the Japan Registry of Clinical Trials (jRCT) on 3 March 2022. Written informed consent is obtained from all patients and/or their guardians. The results of this study will be disseminated through peer-reviewed publications and conference presentations. TRIAL REGISTRATION NUMBER: jRCTs041210154.

Transduodenal ampullectomy for early ampullary cancer: Clinical management, histopathological findings and long-term outcomes at a single center.

BACKGROUND: Transduodenal ampullectomy has been attempted in ampullary tumors, including early ampullary cancer. However, the indication and extent of transduodenal ampullectomy with curative intent remain controversial. Herein, we address the perioperative and long-term outcomes of patients with early ampullary cancer who underwent transduodenal ampullectomy at a single center. METHODS: We retrospectively enrolled 10 early ampullary cancer patients who underwent transduodenal ampullectomy and 11 early ampullary cancer patients who underwent subtotal stomach-preserving pancreatoduodenectomy at Saitama Cancer Center between October 2008 and May 2021. Among this cohort, we analyzed the perioperative outcomes and long-term outcomes. RESULTS: In terms of the perioperative outcomes between the transduodenal ampullectomy and subtotal stomach-preserving pancreatoduodenectomy groups, the transduodenal ampullectomy group exhibited a shorter operating time (244 minutes vs 390 minutes, P = .003), less intraoperative blood loss (67.5 grams vs 774 grams, P = .006) and shorter length of postoperative hospital stay (15 days vs 33 days). With respect to the postoperative nutrition status, the transduodenal ampullectomy group exhibited less postoperative weight loss (0.67% vs 8.95%, P = .021), a better Controlling Nutritional Status score (1.0 vs 2.1, P = .011) and a better Prognostic Nutritional Index score (42.9 vs 40.9, P = .018). The 5-year survival in the adenoma with high-grade dysplasia and T1 ampullary cancer which invaded the mucosal layer groups was 100%, whereas the median survival time in the T1 ampullary cancer which invaded the sphincter of Oddi group was 20.7 months (P = .0028). CONCLUSION: Transduodenal ampullectomy is assumed to be a feasible and effective surgical procedure for the treatment of selected patients with early ampullary cancer, including patients with adenoma with high-grade dysplasia or T1 ampullary cancer which invaded the mucosal layer ampullary cancer.

Epidemiology conduction of paediatric rheumatic diseases based on the registry database of the Pediatric Rheumatology Association of Japan.

OBJECTIVES: Although epidemiological surveys of paediatric rheumatic diseases in Japan have been conducted, they were single surveys with no continuity. This is the first report of the Pediatric Rheumatology Association of Japan registry database, which was established to continuously collect data for paediatric rheumatic diseases. METHODS: Pediatric Rheumatology International Collaborate Unit Registry version 2 (PRICUREv2) is a registry database established by the Pediatric Rheumatology Association of Japan. The registry data were analysed for the age of onset, time to diagnosis, sex differences, seasonality, and other factors. RESULTS: Our data showed the same trend regarding rates of paediatric rheumatic diseases reported in Japan and other countries. The age of onset was lower in juvenile idiopathic arthritis (JIA) and juvenile dermatomyositis and higher in systemic lupus erythematosus and Sjögren's syndrome. The time to diagnosis was relatively short in JIA and systemic lupus erythematosus but longer in juvenile dermatomyositis and Sjögren's syndrome. Rheumatoid factor-positive polyarticular JIA showed a seasonality cluster with regard to onset. CONCLUSION: PRICUREv2 aided the retrieval and evaluation of current epidemiological information on patients with paediatric rheumatic diseases. It is expected that the data collection will be continued and will be useful for expanding research in Japan.

Plasma-derived factor VIIa and factor X mixture agent (MC710) prophylaxis in haemophilia B patients with inhibitors.

INTRODUCTION: Haemophilia B patients with factor IX inhibitors have particularly unmet needs for conventional therapy. AIM: Phase II/III clinical trial, multicentre, open-label, prospective, self-controlled study was conducted to assess MC710 prophylaxis in haemophilia B patients with inhibitors. METHODS: We enrolled haemophilia patients who had received episodic or prophylactic treatment with bypassing agents up to that time. The participants continued their conventional therapy for 24 weeks and then MC710 was prophylactically infused intravenously every 2 or 3 days at 60 to 120 µg as FVIIa per kilogram of body weight for 24 weeks. The primary endpoint was the annual bleeding rate (ABR) requiring bypassing agents, which was compared intraindividually between the conventional therapy period and the MC710 prophylaxis period. RESULTS: A total of 11 male haemophilia B patients were enrolled. The median ABR ratio for each participant (the prophylaxis period ABR divided by the conventional therapy period ABR) was .33 (2.1/6.5), range from .00 to 3.77. ABR ratios for 9 of the 11 patients ranged from .00 to .60, and 3 of the 9 patients had zero bleeding events during the prophylaxis period. Meanwhile, ABR ratios for the remaining two patients were 2.53 and 3.77, respectively. Although a fibrinogen decrease recovered by the dose reduction was reported for only one participant as the sole adverse drug reaction in this study, no thrombotic events or other safety concerns were reported. CONCLUSION: MC710 prophylaxis is considered to be decrease the bleeding rate in haemophilia B patients with inhibitors without safety concerns.

Changes in Muscle Shear Modulus and Urinary Titin N-Terminal Fragment after Eccentric Exercise.

This study aimed to investigate the relationship between the muscle shear modulus of the biceps brachii, urinary titin N-terminal fragment (UTF), and other damage markers after eccentric exercise. Seventeen healthy males performed five sets of ten eccentric exercises with dumbbells weighing 50% of the maximum voluntary contraction (MVC) at the elbow joint. Muscle shear modulus with range of interest set to only biceps brachii muscle measured by ultrasound shear wave elastography, UTF, MVC, range of motion (ROM), and soreness (SOR) were recorded before, immediately after, and 1, 24, 48, 72, 96, and 168 h after eccentric exercise. Each marker changed in a time course pattern, as found in previous studies. The peak shear modulus showed a moderate negative correlation with peak MVC (r = -0.531, P < 0.05) and a strong positive correlation with peak UTF (r = 0.707, P < 0.01). Our study results revealed a significant relationship between muscle strength, shear modulus measured by ultrasound SWE, and titin measured by UTF, as a non-invasive damage marker after eccentric exercise to track changes in EIMD.

Monitoring of Post-Brain Injuries By Measuring Plasma Levels of Neuron-Derived Extracellular Vesicles.

Background: Extracellular vesicles (EV) released from neurons into the blood can reflect the state of nervous tissue. Measurement of neuron derived EV (NDE) may serve as an indicator of brain injury. Methods: A sandwich immunoassay was established to measure plasma NDE using anti-neuron CD171 and anti-EV CD9 ([CD171 + CD9+]). Plasma samples were obtained from commercial sources, cross-country (n = 9), football (n = 22), soccer (n = 19), and rugby (n = 18) athletes over time. Plasma was also collected from patients undergoing total aortic arch replacement (TAR) with selective cerebral perfusion during cardiopulmonary bypass before and after surgery (n = 36). Results: The specificity, linearity, and reproducibility of NDE assay (measurement of [CD171 + CD9+]) were confirmed. By scanning electron microscopy and nanoparticle tracking, spherical vesicles ranging in size from 150 to 300 nm were confirmed. Plasma levels of NDE were widely spread over 2 to 3 logs in different individuals with a significant age-dependent decrease. However, NDE were very stable in each individual within a ± 50% change over time (cross-country, football, soccer), whereas rugby players were more variable over 4 years. In patients undergoing TAR, NDE increased rapidly in days post-surgery and were significantly (P = .0004) higher in those developing postoperative delirium (POD) (n = 13) than non-delirium patients (n = 23). Conclusions: The blood test to determine plasma levels of NDE was established by a sandwich immunoassay using 2 antibodies against neuron (CD171) and exosomes (CD9). NDE levels varied widely in different individuals and decreased with age, indicating that NDE levels should be considered as a normalizer of NDE biomarker studies. However, NDE levels were stable over time in each individual, and increased rapidly after TAR with greater increases associated with patients developing POD. This assay may serve as a surrogate for evaluating and monitoring brain injuries.

Three-dimensional simulation of the pancreatic parenchyma, pancreatic duct and vascular arrangement in pancreatic surgery using a deep learning algorithm.

Three-dimensional surgical simulation, already in use for hepatic surgery, can be used in pancreatic surgery. However, some problems still need to be overcome to achieve more precise pancreatic surgical simulation. The present study evaluates the performance of SYNAPSE VINCENT® (version 6.6, Fujifilm Medical Co., Ltd., Tokyo, Japan) in the semiautomated surgical simulation of the pancreatic parenchyma, pancreatic ducts, and peripancreatic vessels using an artificial intelligence (AI) engine designed with deep learning algorithms. One-hundred pancreatic cancer patients and a control group of 100 nonpancreatic cancer patients were enrolled. The evaluation methods for visualizing the extraction were compared using the Dice coefficient (DC). In the pancreatic cancer patients, tumor size, position, and stagewise correlations with the pancreatic parenchymal DC were analyzed. The relationship between the pancreatic duct diameter and the DC, and between the manually and AI-measured diameters of the pancreatic duct were analyzed. In the pancreatic cancer/control groups, the pancreatic parenchymal DC and pancreatic duct extraction were 0.83/0.86 and 0.84/0.77. The DC of the arteries (portal veins/veins) and associated sensitivity and specificity were 0.89/0.88 (0.89/0.88), 0.85/0.83 (0.85/0.82), and 0.82/0.81 (0.84/0.81), respectively. No correlations were observed between pancreatic parenchymal DC and tumor size, position, or stage. No correlation was observed between the pancreatic duct diameter and the DC. A positive correlation (r = 0.61, p<0.001) was observed between the manually and AI-measured diameters of the pancreatic duct. Extraction of the pancreatic parenchyma, pancreatic duct, and surrounding vessels with the SYNAPSE VINCENT® AI engine assumed to be useful as surgical simulation.

Ice slurry ingestion improves physical performance during high-intensity intermittent exercise in a hot environment.

Ice slurry ingestion enhances exercise performance by lowering the core body temperature. However, an operational issue related to this ingestion is the requirement for a high intake of 7.5 g·kg-1 to produce the desired effects. We investigated the effects of the intake of low amounts of ice slurry at -2°C on the tympanic temperature and exercise performance during repeated high-intensity intermittent exercises in a hot environment. This study was a randomized, crossover study, with a 6-day washout period. Twelve university rugby union players performed two 30-min sessions of high-intensity intermittent exercises separated by a 15-min half-time break on a cycle ergometer in a hot environment (28.8°C ± 0.1°C, 49.5% ± 0.6% relative humidity). The participants ingested 450 g of -2°C-ice slurry (ICE), or a 30°C-beverage (CON) having the same composition as ICE, or 30°C-water (WAT) during the half-time break. The tympanic temperature and skin temperature were measured as the physiological data, and the peak power and mean power as the exercise performance data. The tympanic temperature at the half-time break and beginning of the 2nd session was significantly lower in the ICE group as compared with the CON and WAT groups. The skin temperature at the half-time break was significantly lower in the ICE group as compared with the WAT group. While the peak power and mean power during the 2nd session were significantly greater in the ICE group as compared with the CON and WAT groups. Our findings suggest that even the intake of lower amounts, as compared with those used in previous studies, of low-temperature ice slurry can reduce the body temperature and improve the peak power. These results suggest that intake of low-temperature ice slurry as a strategy for internal body cooling is useful for improving endurance exercise performance in hot environments.

The gs3 allele from a large-grain rice cultivar, Akita 63, increases yield and improves nitrogen-use efficiency.

The Green Revolution allowed a large amount of nitrogen (N) fertilization to increase crop yield but has led to severe environmental pollution. Therefore, increasing the crop grain yield must be achieved without such considerable input of N fertilization. A large-grain japonica rice cultivar, Akita 63, significantly increased grain yield and improved N-use efficiency (NUE) for yield per amount of N absorbed by plants. This study found that the nonsense mutated GS3 gene, the gs3 allele of Akita 63, has a superior yield production with enlarged grain size. The gs3 allele increased the yield with improvements in harvest index and NUE for yields per plant N content by analyzing the near-isogenic line of rice plants with a large grain (LG-Notohikari), which was developed by introducing the gs3 allele of Akita 63 into normal-grain japonica cultivar, Notohikari. Thus, the gs3 allele would be promising for further yield increase without additional large input of N fertilization in non-gs3-allele rice varieties.

Conversion surgery for initially unresectable advanced biliary tract cancer treated with gemcitabine plus cisplatin combination chemotherapy: a case report and literature review.

Recently, the number of reports describing patients with initially unresectable biliary tract cancer (BTC) who underwent resection in the form of conversion surgery is increasing. Gemcitabine plus cisplatin (GC) combination therapy has been reported to significantly prolong the median survival time from 8.1 to 11.7 months compared with conventional gemcitabine therapy in patients with unresectable BTC. We report the case of a patient with unresectable BTC who underwent conversion surgery with a partial response to GC combination therapy. A 78-year-old woman was diagnosed with unresectable BTC with invasion of the right hepatic artery by lymph node metastasis and liver metastases. The patient received GC combination therapy. After 6 cycles of chemotherapy, the patient achieved a partial response. The radiological findings revealed a marked shrinkage in the primary lesion and the disappearance of lymph node and liver metastases. Therefore, the patient underwent conversion surgery, including biliary tract resection and regional lymph node dissection. For postoperative follow-up, the patient was monitored without receiving adjuvant chemotherapy. The patient had not exhibited recurrence during the 12-month follow-up period. We report the case of a patient with unresectable BTC who underwent conversion surgery with a partial response to GC combination therapy.

[Fecal microbiota transplantation for refractory Clostridioides difficile infection with Crohn's disease in an allogeneic bone marrow transplant recipient].

We report a case of a 15-year-old girl who developed refractory Clostridioides difficile infection (CDI) after allogeneic bone marrow transplantation (BMT). She was treated successfully with fecal microbiota transplantation (FMT). The patient who had aplastic anemia underwent allogeneic BMT from an HLA 1-locus-mismatched unrelated donor. Four months later, she developed gastrointestinal graft-versus-host disease (GVHD), and immunosuppressive treatment improved the GVHD. However, she developed CDI 5 months after BMT and experienced recurrence after that. Fifteen months after transplant, CDI relapsed despite discontinuation of immunosuppressive treatment; thus, she underwent FMT. Colonoscopy at the time of FMT revealed round aphthae, mainly in the ileocecum, and colonic biopsy revealed inflammatory cell infiltration and noncaseating epithelioid granuloma, which fulfilled the diagnostic criteria for Crohn's disease. Following FMT for CDI, she was treated with enteric budesonide and intravenous methotrexate for Crohn's disease. These interventions resulted in a marked improvement in both CDI and Crohn's disease. Twenty-eight months after FMT, both CDI and Crohn's disease remained in remission with oral mesalamine monotherapy.

Photosynthetic Enhancement, Lifespan Extension, and Leaf Area Enlargement in Flag Leaves Increased the Yield of Transgenic Rice Plants Overproducing Rubisco Under Sufficient N Fertilization.

BACKGROUND: Improvement in photosynthesis is one of the most promising approaches to increase grain yields. Transgenic rice plants overproducing Rubisco by 30% (RBCS-sense rice plants) showed up to 28% increase in grain yields under sufficient nitrogen (N) fertilization using an isolated experimental paddy field (Yoon et al. in Nat Food 1:134-139, 2020). The plant N contents above-ground sections and Rubisco contents of the flag leaves were higher in the RBCS-sense plants than in the wild-type rice plants during the ripening period, which may be reasons for the increased yields. However, some imprecise points were left in the previous research, such as contributions of photosynthesis of leaves below the flag leaves to the yield, and maintenance duration of high photosynthesis of RBCS-sense rice plants during ripening periods. RESULT: In this research, the photosynthetic capacity and canopy architecture were analyzed to explore factors for the increased yields of RBCS-sense rice plants. It was found that N had already been preferentially distributed into the flag leaves at the early ripening stage, contributing to maintaining higher Rubisco content levels in the enlarged flag leaves and extending the lifespan of the flag leaves of RBCS-sense rice plants throughout ripening periods under sufficient N fertilization. The higher amounts of Rubisco also improved the photosynthetic activity in the flag leaves throughout the ripening period. Although the enlarged flag leaves of the RBCS-sense rice plants occupied large spatial areas of the uppermost layer in the canopy, no significant prevention of light penetration to leaves below the flag leaves was observed. Additionally, since the CO2 assimilation rates of lower leaves between wild-type and RBCS-sense rice plants were the same at the early ripening stage, the lower leaves did not contribute to an increase in yields of the RBCS-sense rice plants. CONCLUSION: We concluded that improvements in the photosynthetic capacity by higher leaf N and Rubisco contents, enlarged leaf area and extended lifespan of flag leaves led to an increase in grain yields of RBCS-sense rice plants grown under sufficient N fertilization.