Trastuzumab deruxtecan in HER2-positive advanced gastric cancer: exploratory biomarker analysis of the randomized, phase 2 DESTINY-Gastric01 trial.

Trastuzumab deruxtecan (T-DXd) showed statistically significant clinical improvement in patients with human epidermal growth factor receptor 2-positive (HER2+) gastric cancer in the DESTINY-Gastric01 trial. Exploratory results from DESTINY-Gastric01 suggested a potential benefit in patients with HER2-low gastric cancer. Spatial and temporal heterogeneity in HER2 expression or gene alteration, an inherent characteristic of gastric cancer tumors, presents a challenge in identifying patients who may respond to T-DXd. Specific biomarkers related to therapeutic response have not been explored extensively. Exploratory analyses were conducted to assess baseline HER2-associated biomarkers in circulating tumor DNA and tissue samples, and to investigate mechanisms of resistance to T-DXd. Baseline HER2-associated biomarkers were correlated with objective response rate (ORR) in the primary cohort of patients with HER2+ gastric cancer. The primary cohort had 64% concordance between HER2 positivity and HER2 (ERBB2) plasma gene amplification. Other key driver gene amplifications, specifically MET, EGFR and FGFR2, in circulating tumor DNA were associated with numerically lower ORR. Among 12 patients with HER2 gain-of-function mutations, ORR was 58.3% (7 of 12). ORR was consistent regardless of timing of immunohistochemistry sample collection. Further investigations are required in larger studies.

Helicobacter cinaedi Infections in Emergency Departments: A Descriptive Study.

AIM: Helicobacter cinaedi, a Gram-negative spiral bacterium, is a rare cause of bacteremia in humans. Unfortunately, little is known about H. cinaedi infections in emergency departments (EDs). We aimed to describe the clinical features of H. cinaedi infections in the ED. METHODS: We conducted a descriptive study at the ED of Kobe City General Hospital (KCGH) in Japan between November 2011 and December 2020. We included all ED patients with H. cinaedi infections. We retrospectively obtained the patient data from electronic medical records and described the patient characteristics, clinical course, and management of H. cinaedi infections. RESULTS: A total of 22 patients in the ED were diagnosed with H. cinaedi infections, and all of them were detected through blood cultures. The chief complaints were vague: fever (18/22, 81.8%), chills (10/22, 45.5%), and localized pain or tenderness (8/22, 36.4%). Patients with complicated cases were also reported in the ED; three patients had vertebral osteomyelitis, two had infected aortic aneurysms, and another two had infected cysts (renal cyst and pancreatic cyst with concomitant empyema). Tetracycline (minocycline) was primarily prescribed and administered intravenously in five of 15 (33.3%) and orally in nine of 20 (45.0%) patients. Only one (4.5%) patient required surgical interventions. None of the patients died in the hospital. CONCLUSIONS: We reported the clinical features of H. cinaedi infections in the ED. Although some patients developed complicated infections, the prognosis was not poor under appropriate treatment, and most of them were successfully treated with antibiotics, primarily tetracycline.

The significance of information and communication technology education via tablets in college of physical therapy.

[Purpose] This study aimed to clarify whether collaborative learning could be promoted via information and communication technology education using tablets at college of physical therapy. [Participants and Methods] An online survey was conducted to evaluate collaborative learning among 81 first-year students at the Department of Physical Therapy actively using tablets in classes (six specific categories). [Results] The Friedman test had significant results, and a significant primary effect was observed between each questionnaire item. Following this, the Bonferroni test was performed for multiple comparisons, with significant differences were observed among certain items. [Conclusion] We reported employing tablets in the classroom positively impacted collaborative learning. Here, among the evaluations of collaborative learning, the items with the best results corresponded mainly to communication activation between students.

COVID-19-associated leukoencephalopathy in the absence of severe hypoxia with subsequent improvement: a case report.

BACKGROUND: Several cases of coronavirus disease 2019 (COVID-19)-associated leukoencephalopathy have been reported. Although most cases involve hypoxia, the pathophysiological mechanism and neurologic outcomes of COVID-19-associated leukoencephalopathy remain unclear. CASE PRESENTATION: We report a case of COVID-19-associated leukoencephalopathy without severe hypoxia in a 65-year-old woman diagnosed with pyelonephritis. After the initiation of intravenous ceftriaxone, her fever resolved, but she developed an altered state of consciousness with abnormal behavior and, subsequently, a relapse fever. She was diagnosed with COVID-19 pneumonia and was intubated. Lung-protective ventilation with deep sedation and neuromuscular blockade were used for treatment. After cessation of sedative administration, her mental status remained at a Glasgow Coma Scale score of 3. COVID-19 was assumed to have caused leukoencephalopathy due to the absence of severe hypoxia or other potential causes. She subsequently showed gradual neurologic improvement. Three months after the COVID-19 diagnosis, she regained alertness, with a Glasgow Coma Scale score of 15. CONCLUSION: Clinicians should consider leukoencephalopathy in the differential diagnosis of consciousness disorders in patients with severe COVID-19, even in the absence of severe hypoxia. Gradual neurologic improvement can be expected in such cases.

External validation of simplified out-of-hospital cardiac arrest and cardiac arrest hospital prognosis scores in a Japanese population: a multicentre retrospective cohort study.

BACKGROUND: The novel simplified out-of-hospital cardiac arrest (sOHCA) and simplified cardiac arrest hospital prognosis (sCAHP) scores used for prognostication of hospitalised patients have not been externally validated. Therefore, this study aimed to externally validate the sOHCA and sCAHP scores in a Japanese population. METHODS: We retrospectively analysed data from a prospectively maintained Japanese database (January 2012 to March 2013). We identified adult patients who had been resuscitated and hospitalised after intrinsic out-of-hospital cardiac arrest (OHCA) (n=2428, age ≥18 years). We validated the sOHCA and sCAHP scores with reference to the original scores in predicting 1-month unfavourable neurological outcomes (cerebral performance categories 3-5) based on the discrimination and calibration measures of area under the receiver operating characteristic curves (AUCs) and a Hosmer-Lemeshow goodness-of-fit test with a calibration plot, respectively. RESULTS: In total, 1985/2484 (82%) patients had a 1-month unfavourable neurological outcome. The original OHCA, sOHCA, original cardiac arrest hospital prognosis (CAHP) and sCAHP scores were available for 855/2428 (35%), 1359/2428 (56%), 1130/2428 (47%) and 1834/2428 (76%) patients, respectively. The AUCs of simplified scores did not differ significantly from those of the original scores, whereas the AUC of the sCAHP score was significantly higher than that of the sOHCA score (0.88 vs 0.81, p<0.001). The goodness of fit was poor in the sOHCA score (ν=8, χ2=19.1 and Hosmer-Lemeshow test: p=0.014) but not in the sCAHP score (ν=8, χ2=13.5 and Hosmer-Lemeshow test: p=0.10). CONCLUSION: The performances of the original and simplified OHCA and CAHP scores in predicting neurological outcomes in successfully resuscitated OHCA patients were acceptable. With the highest availability, similar discrimination and good calibration, the sCAHP score has promising potential for clinical implementation, although further validation studies to evaluate its clinical acceptance are necessary.

Rapid coupling between solid earth and ice volume during the Quaternary.

The solid earth plays a major role in controlling Earth's surface climate. Volcanic degassing of carbon dioxide (CO2) and silicate chemical weathering are known to regulate the evolution of climate on a geologic timescale (> 106 yr), but the relationship between the solid earth and the shorter (< 105 yr) fluctuations of Quaternary glacial-interglacial cycles is still under debate. Here we show that the seawater osmium isotope composition (187Os/188Os), a proxy for the solid earth's response to climate change, has varied during the past 300,000 years in association with glacial-interglacial cycles. Our marine Os isotope mass-balance simulation reveals that the observed 187Os/188Os fluctuation cannot be explained solely by global chemical weathering rate changes corresponding to glacial-interglacial climate changes, but the fluctuation can be reproduced by taking account of short-term inputs of (1) radiogenic Os derived from intense weathering of glacial till during deglacial periods and (2) unradiogenic Os derived from enhanced seafloor hydrothermalism triggered by sea-level falls associated with increases of ice sheet volume. Our results constitute the first evidence that ice sheet recession and expansion during the Quaternary systematically and repetitively caused short-term (< 105 yr) solid earth responses via chemical weathering of glacial till and seafloor magmatism. This finding implies that climatic changes on < 105 yr timescales can provoke rapid feedbacks from the solid earth, a causal relationship that is the reverse of the longer-term (> 106 yr) causality that has been conventionally considered.

Pre-existing psychiatric disorder is related to lower mortality from road traffic accident: A Japanese nationwide retrospective cohort study.

BACKGROUND: Previous studies have reported inconsistent results on the mortality from trauma among psychiatric patients comparing to non-psychiatric population, which may be partly explained by the inclusion of both suicidal and accidental trauma. This study aimed to investigate the association of psychiatric diagnoses on admission with the outcomes of hospitalized patients for accidental trauma, namely road traffic injury. METHODS: Detailed information of patients aged 15 years or older who were hospitalized for road traffic injury between 2004 and 2017 was extracted from the Japan Trauma Data Bank. The primary outcome was to compare in-hospital mortality between patients with and without a psychiatric disorder. We also conducted a subgroup analysis among patients with and without a serious head injury. RESULTS: Altogether, 85,069 patients were included. Of these, 3,895 patients (4.6%) had a psychiatric diagnosis. The in-hospital mortality rate was significantly lower among patients with a psychiatric diagnosis than those without (5.4% vs. 8.3%; adjusted odds ratio [OR] 0.57, 95% confidence interval [CI] 0.47-0.70, p<0.001). In a subgroup analysis of patients with a serious head injury, in-hospital mortality was significantly lower in patients with a psychiatric diagnosis than in those without (10.5% vs. 17.3%; adjusted OR 0.48, 95% CI 0.37-0.62, p<0.001); in-hospital mortality of patients without a serious head injury showed no differences between patients with or without a psychiatric diagnosis (2.8% vs. 3.5%; adjusted OR 0.84, 95% CI 0.61-1.16, p=0.295). CONCLUSIONS: In-hospital mortality from road traffic injury was significantly lower among patients with a psychiatric diagnosis than those without, which was primarily evident in a subgroup of patients with a serious head injury. While further replication is necessary, results might be indicative of the neuroprotective effect of psychotropic medications.

Critically ill patients with COVID-19 in Tokyo, Japan: A single-center case series.

INTRODUCTION: We reported, in our previous study, a patient with coronavirus disease 2019 (COVID-19) who was successfully treated with extracorporeal membrane oxygenation. Data on clinical courses and outcomes of critically ill patients with COVID-19 in Japan are limited in the literature. This study aimed to describe the clinical courses and outcomes of critically ill patients with COVID-19 in Tokyo, Japan. METHODS: This is a single-center case series study. Patients with COVID-19 treated with mechanical ventilation (MV) were reviewed retrospectively. Data on baseline characteristics, in-hospital treatment, and outcomes were collected. RESULTS: Between February 2, 2020, and June 30, 2020, 14 critically ill patients with COVID-19 were treated with MV. Most patients were male and had comorbidities, especially hypertension or diabetes; 35.7% were overweight and 21.4% were obese. The majority of the patients had dyspnea on admission. The median duration of MV was 10.5 days, and the 28-day mortality rate was 35.7%. In the four patients with COVID-19 who died, the cause of death was respiratory failure. CONCLUSIONS: As in previous reports from other countries, the mortality rate of patients with COVID-19 requiring intensive care remains high in Tokyo. Further study on the appropriate timing of MV initiation and specific treatments for critically ill patients with COVID-19 is needed.

Lower mortality from suicidal trauma among patients with a psychiatric diagnosis upon admission: Nationwide japanese retrospective cohort study.

Suicide and self-harm are major public health issues. Few studies have compared mortality from suicidal trauma between patients with and without contact with psychiatric services. This study aimed to compare the in-hospital mortality of suicidal trauma between patients with and without a psychiatric diagnosis upon hospital admission. Data on 15- to 90-year-old patients with suicidal trauma between 2004 and 2015 was extracted from the Japan Trauma Data Bank. In-hospital mortality were compared between patients with and without a psychiatric diagnosis. A total of 9,803 patients were included. The median age was 42 years (interquartile range: 29-59), and 5,010 patients (51.1%) were male. The most frequent method of injury was falling from a height (53.4%), followed by stabbing (32.3%) and burns (6.2%). In total, 4,878 patients (49.8%) had a psychiatric diagnosis upon admission. The proportion of patients with a psychiatric diagnosis was significantly lower among males, teenagers, and older people. In-hospital mortality was significantly lower among patients with a psychiatric diagnosis than those without (10.9%vs18.7%). Contact with psychiatric services might be protective among people with suicidal trauma. However, the proportion of psychiatric service use was generally low. These findings show the importance of delivering appropriate psychiatric services to high-risk patients.

Tension pneumoperitoneum caused by intestinal perforation from underlying colon cancer: a case report.

BACKGROUND: Tension pneumoperitoneum, a form of abdominal compartment syndrome, is an important clinical condition. Increased pressure in the intraperitoneal cavity leads to respiratory and circulatory instability. Most of the reported cases include complications due to active air infusion into the peritoneal cavity or trauma; however, few reports are available on tension pneumoperitoneum caused by perforation from colon cancer. We present a case of a patient with tension pneumoperitoneum caused by gastrointestinal perforation owing to colon cancer. CASE PRESENTATION: A 63-year-old Japanese man with altered mental state was brought to our emergency department. He was in shock, and an abdominal radiograph suggested gastrointestinal perforation. Despite rapid fluid infusion and inotropic support, his condition deteriorated. His abdomen was tensely distended; abdominal computed tomography showed significant intra-abdominal gas. Following immediate needle decompression, his circulatory status improved. Emergent laparotomy revealed an approximately 10-cm tumor (adenocarcinoma) in the colon, which caused the perforation. CONCLUSIONS: A perforated wall or the surrounding omental fat that acts as a one-way valve could lead to tension pneumoperitoneum without active air infusion. Although tension pneumoperitoneum is a life-threatening condition, it is reversible if prompt diagnosis and immediate decompression are performed. Physicians should always consider this condition as one of the causes of shock or cardiopulmonary arrest, even without an apparent medical history of active air infusion or trauma.

A sporadic COVID-19 pneumonia treated with extracorporeal membrane oxygenation in Tokyo, Japan: A case report.

INTRODUCTION: An ongoing outbreak of a novel coronavirus disease (coronavirus disease 2019, COVID-19) has become a global threat. While clinical reports from China to date demonstrate that the majority of cases remain relatively mild and recover with supportive care, it is also crucial to be well prepared for severe cases warranting intensive care. Initiating appropriate infection control measures may not always be achievable in primary care or in acute-care settings. CASE: A 45-year-old man was admitted to the intensive care unit due to severe pneumonia, later confirmed as COVID-19. His initial evaluation in the resuscitation room and treatments in the intensive care unit was performed under droplet and contact precaution with additional airborne protection using the N95 respirator mask. He was successfully treated in the intensive care unit with mechanical ventilation and extracorporeal membrane oxygenation for respiratory support; and antiretroviral treatment with lopinavir/ritonavir. His total intensive care unit stay was 15 days and was discharged on hospital day 24. CONCLUSIONS: Strict infection control precautions are not always an easy task, especially under urgent care in an intensive care unit. However, severe cases of COVID-19 pneumonia, or another novel infectious disease, could present at any moment and would be a continuing challenge to pursue appropriate measures. We need to be well prepared to secure healthcare workers from exposure to infectious diseases and nosocomial spread, as well as to provide necessary intensive care.

Private residence as a location of cardiac arrest may have a deleterious effect on the outcomes of out-of-hospital cardiac arrest in patients with an initial non-shockable cardiac rhythm: A multicentre retrospective cohort study.

AIM: We compared the outcomes between patients who experienced out-of-hospital cardiac arrest at private residences and public locations to investigate whether patient and bystander characteristics can explain the poorer outcomes of out-of-hospital cardiac arrests at private residences. METHODS: Adult patients with intrinsic out-of-hospital cardiac arrest (n = 6,191, age ≥18 years) were selected from a prospectively collected Japanese database (January 2012 and March 2013). Patients were grouped according to arrest location into private-residence or control (e.g., public station or road, workplace, school, and other public locations) groups. The primary outcome was a favourable neurological outcome 1 month after out-of-hospital cardiac arrest. RESULTS: The arrest location and initial cardiac rhythm had interaction effects on the outcome. After adjusting for patient and bystander characteristics and relative to the control group, a significantly poorer 1-month neurological outcome was observed in the private-residence group if the initial cardiac rhythm was non-shockable (odds ratio: 0.36, 95% confidence interval: 0.24-0.54), while it was not significant if the initial cardiac rhythm was shockable (odds ratio: 1.16, 95% confidence interval: 0.74-1.84). CONCLUSIONS: Patients with out-of-hospital cardiac arrest at private residences had poorer outcomes than those with out-of-hospital cardiac arrest at public locations, even after adjusting for patient and bystander characteristics, if the initial cardiac rhythm was non-shockable. Our results suggest that poorer patient and bystander characteristics do not completely explain the poorer outcomes of out-of-hospital cardiac arrests; there may be unknown mechanisms through which the location of cardiac arrest affect the outcomes.

Prehospital times and outcomes of patients who had hypotension at the scene after trauma: A nationwide multicentre retrospective study.

BACKGROUND: We aimed to investigate the association between prehospital times and outcomes of patients who had hypotension at the scene after trauma incidents. METHODS: We retrospectively analysed records from a nationwide database (2004-2017) of adults (aged ≥15 years) who were hypotensive (systolic blood pressure <90 mmHg) at the scene after trauma. The endpoint was in-hospital mortality. We used multivariable logistic regression analysis to adjust for confounding factors and to estimate the odds ratio (OR) of prehospital times for in-hospital mortality. Stratified analyses were performed based on patient age and type and severity of the trauma. RESULTS: Among 5,499 patients included, 906 (16.5%) died in the hospital. The median Injury Severity Score (ISS) was 17 (interquartile range, 9-29). There was a significant trend towards patients having higher in-hospital mortality and ISS when their prehospital times were shorter (P < 0.001). However, the association between prehospital times and in-hospital mortality was not significant after adjusting for confounding factors, with an adjusted odds ratio of 1.00 (95% confidence interval: 0.98-1.01) per 10 min increments in prehospital time. The association remained insignificant when patients were stratified according to age and type and severity of the trauma. CONCLUSIONS: Our analysis revealed that prehospital time was not significantly associated with in-hospital mortality among patients who had hypotension at the scene after trauma in the current emergency medical service system in Japan. Further studies are needed to validate our findings.

Epidemiological state, predictive model for mortality, and optimal management strategy for pancreatic injury: A multicentre nationwide cohort study.

BACKGROUND: Data for establishing the optimal management modalities for pancreatic injury are lacking. Herein, we aimed to describe the epidemiology, identify mortality predictors, and determine the optimal management strategy for pancreatic injury. METHODS: We identified patients with pancreatic injury between 2004 and 2017 recorded in the Japan Trauma Data Bank. The primary outcome was mortality. Multivariable logistic regression analyses were used to identify factors significantly associated with mortality and to develop a predictive model. Patients were also classified according to the Organ Injury Scaling of the American Association for the Surgery of Trauma (AAST grade I/II or III/IV). Outcomes were compared based on significant confounder-adjusted treatment strategy. RESULTS: Overall, 743 (0.25%) patients had pancreatic injury. Traffic accident was the most common aetiology. The overall mortality rate was 17.5%, while it was 4.7% for isolated pancreatic injury. AAST grade, Revised Trauma Scale score on arrival, age, and coexistence of severe abdominal injury aside from pancreatic injury were independently associated with mortality. A predictive model for mortality comprising these four variables showed excellent performance, with an area under the receiver operating characteristic curve of 0.89 (95% confidence interval [CI], 0.85-0.93). The in-hospital mortality was higher in patients who underwent celiotomy than in those who did not among those with AAST grade I/II (15.1% vs. 5.3%) and III/IV (13.8% vs. 12.3%). After adjusting for confounders, these differences were not significant with the adjusted odds ratios of 1.41 (95% CI, 0.55-3.60) and 0.54 (95% CI, 0.17-1.67) for AAST grade I/II and III/IV, respectively. CONCLUSIONS: AAST grade, Revised Trauma Scale score on arrival, age, and coexistence of severe abdominal injury aside from pancreatic injury were prognostic factors of mortality after pancreatic injury. Confounder-adjusted analysis did not show that operative management was superior to non-operative management for survival. Non-operative management may be a reasonable strategy for select pancreatic injury patients, especially in institutions where expertise in interventional endoscopy is available.

Effects of dispatcher-initiated telephone cardiopulmonary resuscitation after out-of-hospital cardiac arrest: A nationwide, population-based, cohort study.

AIM: This study aimed to investigate the effects of dispatcher-initiated telephone cardiopulmonary resuscitation (TCPR) in Japan using a nationwide population-based registry. METHODS: Adult Japanese patients with out-of-hospital cardiac arrest (OHCA; n = 582,483, age ≥18 years) were selected from a nationwide Utstein-style database (2010-2016) and divided into 3 groups: no bystander CPR (NCPR) before emergency medical service arrival (n = 448,606), bystander-initiated CPR (BCPR) performed without assistance (n = 46,964), and TCPR (n = 86,913). The primary outcome was a favourable neurological outcome 1 month after OHCA. RESULTS: After adjusting for potential confounders, and relative to the NCPR group, significantly better 1-month neurological outcomes were observed in the BCPR group (odds ratio: 2.25, 95% confidence interval: 2.15-2.36; P < 0.001) and in the TCPR group (odds ratio: 1.30, 95% confidence interval: 1.24-1.36; P < 0.001). The collapse-to-CPR time was independently associated with the 1-month outcomes, with a rate of <1% for 1-month favourable neurological outcomes if CPR was initiated >5 min after the collapse. CONCLUSION: Patients who received TCPR had significantly better outcomes than those who did not receive CPR. However, the TCPR outcomes were less favourable than those in the BCPR group. Better protocol development and enhanced education are needed to improve dispatcher instructions in Japan, which may help lessen the gap between the BCPR and TCPR outcomes and further improve the outcomes after OHCA.

Extracorporeal CPR for massive pulmonary embolism in a "hybrid 2136 emergency department".

AIM: Patients with massive pulmonary embolism (PE) have poor outcomes and their management remains challenging. An interventional radiology (IVR)-computed tomography (CT) system available in our emergency room (ER) allows immediate access to CT and extracorporeal membrane oxygenation (ECMO) with safe cannulation under fluoroscopy. We aimed to determine if initial treatment in this "hybrid ER" is helpful in patients with PE requiring extracorporeal cardiopulmonary resuscitation (ECPR). METHODS: The records of patients transferred to our hybrid ER between September 2014 and December 2017 who required ECPR for PE were reviewed. RESULTS: Nine consecutive patients (median age 50 [range 30-76] years) with PE requiring ECPR were identified in our hybrid ER. Five (55.6%) had at least one risk factor for PE. Six (66.7%) experienced an out-of-hospital cardiac arrest and 3 (33.3%) had a cardiac arrest in the hybrid ER. Right ventricular overload was detected on electrocardiography and bedside transthoracic echocardiography in all cases. The median pH, lactate, PaCO2, and HCO3 values on arterial blood gas analysis in the hybrid ER were 7.01 (6.68-7.26), 14 (8-22) mmol l-1, 44.7 (23.8-60.5) mmHg, and 10.4 (6.7-14.1), respectively. Four patients (44.4%) received monteplase for thrombolysis. No patient underwent surgical embolectomy. The median duration of ECMO was 69 (38-126) h. There were two ECMO-related bleeding complications. Eight patients (88.9%) survived and one died of post-resuscitation encephalopathy after weaning from ECMO. CONCLUSION: A hybrid ER may be useful for initial management of massive PE requiring ECPR and may help to improve outcomes.

Identification of potential genes involved in triterpenoid saponins biosynthesis in Gleditsia sinensis by transcriptome and metabolome analyses.

Gleditsia sinensis is widely used as a medicinal plant in Asia, especially in China. Triterpenes, alkaloids, and sterols were isolated from Gleditsia species. Among them, triterpenoid saponins are very important metabolites owing to their various pharmacological activities. However, the triterpenoid saponin biosynthesis pathway has not been well characterized. In the present study, we performed de novo transcriptome assembly for 14.3 Gbps of clean reads sequenced from nine tissues of G. sinensis. The results showed that 81,511 unique transcripts (unitranscripts) (47,855 unigenes) were constructed, of which 31,717 unigenes were annotated with Gene Ontology and EC numbers by Blast2GO against the NCBI-nr protein database. We also analyzed the metabolite contents in the same nine tissues by LS-MS/MS, and saponins including gleditsioside I were found in fruit at higher levels. Many of the genes with tissue-specific expression in fruit are involved in the flavonoid biosynthesis pathway, and many of those have UDP-glucosyltransferase (UGT) activity. We constructed a saponin biosynthesis pathway and identified two key enzyme families in the triterpenoid saponin biosynthesis pathway, cytochrome P450 and UDP-glucosyltransferase, that are encoded by 37 unigenes and 77 unigenes, respectively. CYP72A, CYP716A, and CYP88D, which are known as key enzymes for saponin biosynthesis, were also identified among the P450s. Our results provide insight into the secondary metabolite biosynthesis and serve as important resources for future research and cultivation of G. sinensis.

Light spectrum regulates cell accumulation during daytime in the raphidophyte Chattonella antiqua causing noxious red tides.

Most marine raphidophyte species cause noxious red tides in temperate coastal areas around the world. It is known that swimming abilities enable raphidophytes to accumulation of cells and to actively acquire light at surface layers and nutrients over a wide depth range. However, it remains unclear how the swimming behavior is affected by environmental conditions, especially light condition. In the present study, we observed the accumulation of the harmful red-tide raphidophyte Chattonella antiqua under various light conditions during the daytime in the laboratory. When exposed to ultraviolet-A/blue light (320-480nm) or red light (640-680nm) from above, cells moved downward. In the case of blue light (455nm), cells started to swim downward after 5-15min of irradiation at a photon flux density≥10µmolm(-2)s(-1). When exposed to monochromatic lights (400-680nm) from the side, cells moved away from the blue light source and then descended, but just moved downward under red light. However, mixing of green/orange light (520-630nm) diminished the effects of blue light. When exposed to a mixture of 30µmolm(-2)s(-1) of blue light (440nm) and ≥6µmolm(-2)s(-1) of yellow light (560nm) from above, cells did not move downward. These results indicate that blue light induces negative phototaxis and ultraviolet-A/blue and red lights induce descending, and green/orange light cancels out their effects in C. antiqua.

Gene expression analysis in the lung of the rasH2 transgenic mouse at week 4 prior to induction of malignant tumor formation by urethane and N-methylolacrylamide.

The rasH2 transgenic (Tg) mice are susceptible to genotoxic and some non-genotoxic carcinogens. In carcinogenicity studies carried out using rasH2 Tg mice, the carcinogenic potential of chemicals are evaluated over a 26-week experimental period. In the present study, we examined the comprehensive gene expressions in the lungs of Tg and non-Tg mice prior to the induction of malignant tumors. Urethane (UR), a mutagenic carcinogen, was administered for 4 weeks, and thereafter withdrawn for 22 weeks. N-methylolacrylamide (NMA), a non-mutagenic carcinogen, was administered for 26 weeks. At week 4, gene expression analysis of non-neoplastic part of the lungs demonstrated changes in the expressions of the cell-cycle and inflammation related genes following UR and NMA treatment, respectively, in both the Tg and non-Tg mice. The gene expressions of epireguline, aurora kinase B, and cyclin B1 increased in the UR-treated Tg mice. We also found an increase in the plasma carcinoembryonic antigen level in the UR-treated Tg mice. Although UR treatment induced the formation of adenomas or adenocarcinomas in the lungs in all mice, earlier induction was apparent in the Tg mice. NMA treatment was found to induce the formation of adenomas and adenocarcinomas at week 26 in the Tg mice, but not in the non-Tg mice, and no expressions of specific genes were apparent in either genotype of mice. Our results indicate that analysis of cancer-related gene expressions in the lungs and plasma biomarkers at week 4 in rasH2 Tg mice could be a screening tool for carcinogenicity, especially of mutagenic carcinogens.

Japan PGx Data Science Consortium Database: SNPs and HLA genotype data from 2994 Japanese healthy individuals for pharmacogenomics studies.

Japan Pharmacogenomics Data Science Consortium (JPDSC) has assembled a database for conducting pharmacogenomics (PGx) studies in Japanese subjects. The database contains the genotypes of 2.5 million single-nucleotide polymorphisms (SNPs) and 5 human leukocyte antigen loci from 2994 Japanese healthy volunteers, as well as 121 kinds of clinical information, including self-reports, physiological data, hematological data and biochemical data. In this article, the reliability of our data was evaluated by principal component analysis (PCA) and association analysis for hematological and biochemical traits by using genome-wide SNP data. PCA of the SNPs showed that all the samples were collected from the Japanese population and that the samples were separated into two major clusters by birthplace, Okinawa and other than Okinawa, as had been previously reported. Among 87 SNPs that have been reported to be associated with 18 hematological and biochemical traits in genome-wide association studies (GWAS), the associations of 56 SNPs were replicated using our data base. Statistical power simulations showed that the sample size of the JPDSC control database is large enough to detect genetic markers having a relatively strong association even when the case sample size is small. The JPDSC database will be useful as control data for conducting PGx studies to explore genetic markers to improve the safety and efficacy of drugs either during clinical development or in post-marketing.