2,2'-Tethered Binaphthyl-Embedded One-Handed Helical Ladder Polymers: Impact of the Tether Length on Helical Geometry and Chiroptical Property.

Synthetic breakthroughs diversify the molecules and polymers available to chemists. We now report the first successful synthesis of a series of optically-pure 2,2'-tethered binaphthyl-embedded helical ladder polymers based on quantitative and chemoselective ladderization by the modified alkyne benzannulations using the 4-alkoxy-2,6-dimethylphenylethynyl group as the alkyne source, inaccessible by the conventional approach lacking the 2,6-dimethyl substituents. Due to the defect-free helix formation, the circular dichroism signal increased by more than 6 times the previously reported value. The resulting helical secondary structure can be fine-tuned by controlling the binaphthyl dihedral angle in the repeating unit with variations in the 2,2'-alkylenedioxy tethering groups by one carbon atom at a time. The optimization of the helical ladder structures led to a strong circularly polarized luminescence with a high fluorescence quantum yield (28 %) and luminescence dissymmetry factor (2.6×10-3 ).

Utility of Blood Culture in Patients with Community-Acquired Pneumonia: A Propensity Score-Matched Analysis Based on a Japanese National Health Insurance Database.

Community-acquired pneumonia (CAP) is an acute pulmonary parenchymal infection acquired outside the hospital. The utility of blood cultures in inpatients with CAP to reduce mortality and length of hospital stay is controversial. This study aimed to determine the utility of blood cultures on the first day of hospitalization for CAP inpatients and its influence on mortality, length of hospital stay, and antibiotics use. We conducted a fact-finding survey on the implementation of blood culture in inpatients with CAP in Japan. A propensity score (PS)-matched analysis based on the National Database of Health Insurance Claims and Specific Health Check-ups of Japan database was conducted. Overall, 163173 patients were included in the analysis, and PS matching extracted 68104 pairs. The results of the comparison between the PS-matched blood culture group and PS-matched control group were as follows: mortality and length of hospital stay were significantly lower in the PS-matched blood culture group than in the control group. The adjusted odds ratio (OR) (95% confidence interval (CI)) for in-hospital mortality with blood culture test was 0.73 (0.68-0.79). Moreover, for days of antibiotic usage, number of antibiotics used were significantly higher in the PS-matched blood culture group than that in the control group. Our findings indicated that performing a blood culture on the first day of hospitalization for inpatients with CAP was associated with reduced mortality. To our knowledge, this is the largest epidemiological study to assess the utility of blood culture in Japanese inpatients with CAP. This testing method shows potential for application in clinical practice.

Preoperative respiratory intervention eliminated the operation cancelations of lobectomy surgery.

In Nagasaki University Hospital, the patients undergoing surgery with abnormal respiratory function have been automatically referred to specialized clinic by Medical Support Center (MSC) since July 2016 to reduce surgery cancellations due to insufficient preoperative evaluation. Whether the MSC system decreased post-hospital surgery cancellation, variance rate, or length of hospital stays in patients received "lobectomy" were retrospectively compared between Period A (n = 264, before MSC introduction) and Period B (n = 264, after MSC introduction). Four patients' operations were cancelled after hospitalization in Period A, while 0 patients in Period B (p < 0.05). The length of hospital stay, operation time, anesthesia time, and postoperative extubation oxygen administration time were all shorten in Period B significantly. "Period B", "operation time", and "postoperation oxygenation time" were independent factors for "hospital days", but chronic obstructive pulmonary disease or age were not. The preoperative intervention eliminated the operation cancellation. Preoperative MSC interventions may have contributed to the reduction in hospital days even for the patients with pulmonary dysfunction.

Coordination of hitting movement revealed in baseball tee-batting.

Baseball batters must react to pitches delivered to different locations within the strike zone by modulating their movements. In tee-batting practice, such batters place a ball on a tee stand at a location, where they intend to hit the ball, assuming a particular pitch's trajectory. In the present study, we analysed three-dimensional movements in tee-batting to identify characteristics of the batters' intended impact locations across the strike zone, thereby investigating spatiotemporal features of movement modulation. More specifically, 10 experienced baseball batters performed tee-batting at their preferred impact locations at nine different heights and courses within the strike zone. The distribution of impact locations showed regularity, i.e., the location shifted forward for balls placed high and inside, while it shifted backward for balls placed low and outside. Furthermore, trunk and arm movements showed systematic modulation as the impact locations changed. The duration of bat movement was also location dependent, i.e., hitting the inside ball took more time than hitting the outside ball. Our results indicate that even though movements among body segments were properly coordinated to adjust the bat swing for different impact locations, fine timing adjustments were also required to hit the ball at those preferred impact locations and therefore properly react to differences in flight paths.

An effective medical partnership in Nagasaki, Japan for patients with rheumatoid arthritis.

OBJECTIVES: A clear division of the roles of inpatient facilities and outpatient clinics treating patients with rheumatoid arthritis (RA) is needed. To address this, we created a medical partnership between a university hospital and 43 community clinics in Nagasaki, Japan. METHODS: We recruited the clinic physicians and compiled a list of the RA medications used (i.e. methotrexate [MTX], other disease-modifying antirheumatic drugs [DMARDs], and biologics). When a patient's low disease activity or remission was confirmed at the university hospital, the hospital/clinic partnership provided double follow-up/medical care with semiannual meetings between the hospital and clinic physicians. RESULTS: We enrolled 149 patients who maintained clinical remission at 43 clinics over a 54-month period, without rare serious events. Among the nine patients who returned to the university hospital due to relapse, 66.7% had exacerbated RA within 18 months. An average 8.8-9.6 mg/week (max. 14 mg/week) MTX dose was prescribed at the clinics. The biologic usage rate was 22.1%, with a yearly increase. Among the patients treated with biologics, the DAS28ESR at enrollment was 2.65, with 58% treated with an MTX/biologic combination. A significant reduced number of patients with RA per rheumatologist were observed. CONCLUSIONS: Maintenance of DAS remission without major adverse events was attained in the medical partnership.

First malaria in pregnancy followed in Philippine real-world setting: proof-of-concept of probabilistic record linkage between disease surveillance and hospital administrative data.

BACKGROUND: Although the Philippines targets malaria elimination by 2030, it remains to be a disease that causes considerable morbidity in provinces that report malaria. Pregnant women residing in endemic areas are a vulnerable population, because in addition to the risk of developing severe malaria, their pregnancy is not followed through, and the outcome of their pregnancy is unknown. This study determined the utility of real-world data integrated with disease surveillance data set as real-world evidence of pregnancy and delivery outcomes in areas endemic for malaria in the Philippines. METHODS: For the period of 2015 to 2019, electronic data sets of malaria surveillance data and Ospital ng Palawan hospital admission log of pregnant women residing in the four selected barangays of Rizal, Palawan were merged using probabilistic linkage. The source data for record linkage were first and last names, birth date, and address as the mutual variable. The data used for characteristics of the pregnant women from the hospital data set were admission date, discharge date, admitting and final diagnosis and body weight on admission. From the malaria surveillance data these were date of consultation, and malaria parasite species. The Levenshtein distance formula was used for a fuzzy string-matching algorithm. Chi-square test, and Mann-Whitney U test were used to compare the means of the two data sets. RESULTS: The prevalence of pregnant women admitted to the tertiary referral hospital, Ospital ng Palawan, was estimated to be 8.34/100 overall, and 11.64/100 from the four study barangays; that of malaria during pregnancy patients was 3.45/100 and 2.64/100, respectively. There was only one true-positive matched case from 238 women from the hospital and 54 women from the surveillance data sets. The overall Levenshstein score was 97.7; for non-matched cases, the mean overall score was 36.6 (35.6-37.7). The matched case was a minor who was hospitalized for severe malaria. The outcome of her pregnancy was detected from neither data set but from village-based records. CONCLUSIONS: This proof-of-concept study demonstrated that probabilistic record linkage could match real-world data in the Philippines with further validation required. The study underscored the need for more integrated and comprehensive database to monitor disease intervention impact on pregnancy and its outcome in the Philippines.

Cell death caused by excision of centromeric DNA from a chromosome in Saccharomyces cerevisiae.

If genetically modified organisms (GMOs) are spread through the natural environment, it might affect the natural environment. To help prevent the spread of GMOs, we examined whether it is possible to introduce conditional lethality by excising centromeric DNA from a chromosome by site-specific recombination in Saccharomyces cerevisiae as model organism. First, we constructed haploid cells in which excision of the centromeric DNA from chromosome IV can occur due to recombinase induced by galactose. By this excision, cell death can occur. In diploid cells, cell death can also occur by excision from both homologous chromosomes IV. Furthermore, cell death can occur in the case of chromosome V. A small number of surviving cells appeared with excision of centromeric DNA, and the diploid showed greater viability than the haploid in both chromosomes IV and V. The surviving cells appeared mainly due to deletion of a recombination target site (RS) from the chromosome.

A global transcriptome analysis of a dog model of congestive heart failure with the human genome as a reference.

BACKGROUND: The global molecular changes in cardiac tissue during congestive heart failure (CHF) have not been fully examined. Transcriptome analysis with the use of next-generation sequencers is a useful tool for elucidating the pathogenesis of CHF. Although there are some advantages in a dog CHF model, transcriptome analyses in dogs are limited by the relative lack of genomic information. METHODS AND RESULTS: The transcriptome analysis of hearts from dogs with CHF was conducted with the use of a genome analyzer and the Casava software. The mRNA sequence reads showed alignments with ∼800 of 1,019 genes from the dog reference database. On the other hand, the reads aligned with ∼15,000 of the 21,407 genes in the hg19 human reference database. The correlation of expressed genes was extremely high (r = 0.93; P < .0001) between the dog and human databases. A pathway analysis using the hg19 reference revealed increased expression of p53 pathway-related (P < 10(-10)) and inflammatory interleukin-related (P < 10(-10)) genes in the CHF model. CONCLUSIONS: The use of the human genome as a reference in global transcriptome analyses of dogs is a useful approach for investigating diseases such as CHF. Such an approach would also be useful for analyzing disease models in other experimental animals.

Public Interest and Accessibility of Telehealth in Japan: Retrospective Analysis Using Google Trends and National Surveillance.

BACKGROUND: Recently, the use of telehealth for patient treatment under the COVID-19 pandemic has gained interest around the world. As a result, many infodemiology and infoveillance studies using web-based sources such as Google Trends were reported, focusing on the first wave of the COVID-19 pandemic. Although public interest in telehealth has increased in many countries during this time, the long-term interest has remained unknown among people living in Japan. Moreover, various mobile telehealth apps have become available for remote areas in the COVID-19 era, but the accessibility of these apps in epidemic versus nonepidemic regions is unknown. OBJECTIVE: We aimed to investigate the public interest in telehealth during the first pandemic wave and after the wave in the first part of this study, and the accessibility of medical institutions using telehealth in the epidemic and nonepidemic regions, in the second part. METHODS: We examined and compared the first wave and after the wave with regards to severe cases, number of deaths, relative search volume (RSV) of telehealth and COVID-19, and the correlation between RSV and COVID-19 cases, using open sources such as Google Trends and the Japanese Ministry of Health, Labour and Welfare (JMHLW) data. The weekly mean and the week-over-week change rates of RSV and COVID-19 cases were used to examine the correlation coefficients. In the second part, the prevalence of COVID-19 cases, severe cases, number of deaths, and the telehealth accessibility rate were compared between epidemic regions and nonepidemic regions, using the JMHLW data. We also examined the regional correlation between telehealth accessibility and the prevalence of COVID-19 cases. RESULTS: Among the 83 weeks with 5 pandemic waves, the overall mean for the RSV of telehealth and COVID-19 was 11.3 (95% CI 8.0-14.6) and 30.7 (95% CI 27.2-34.2), respectively. The proportion of severe cases (26.54% vs 18.16%; P<.001), deaths (5.33% vs 0.99%; P<.001), RSV of telehealth (mean 33.1, 95% CI 16.2-50.0 vs mean 7.3, 95% CI 6.7-8.0; P<.001), and RSV of COVID-19 (mean 52.1, 95% CI 38.3-65.9 vs mean 26.3, 95% CI 24.4-29.2; P<.001) was significantly higher in the first wave compared to after the wave. In the correlation analysis, the public interest in telehealth was 0.899 in the first wave and -0.300 overall. In Japan, the accessibility of telehealth using mobile apps was significantly higher in epidemic regions compared to nonepidemic regions in both hospitals (3.8% vs 2.0%; P=.004) and general clinics (5.2% vs 3.1%; P<.001). In the regional correlation analysis, telehealth accessibility using mobile apps was 0.497 in hospitals and 0.629 in general clinics. CONCLUSIONS: Although there was no long-term correlation between the public interest in telehealth and COVID-19, there was a regional correlation between mobile telehealth app accessibility in Japan, especially for general clinics. We also revealed that epidemic regions had higher mobile telehealth app accessibility. Further studies about the actual use of telehealth and its effect after the COVID-19 pandemic are necessary.

Transcriptome analysis of a dog model of congestive heart failure shows that collagen-related 2-oxoglutarate-dependent dioxygenases contribute to heart failure.

Fibrosis is an important pathological mechanism in heart failure (HF) and is associated with poor prognosis. We analyzed fibrosis in HF patients using transcriptomic data. Genes differentially expressed between normal control and congestive HF (CHF) dogs included P3H1, P3H2, P3H4, P4HA2, PLOD1 and PLOD3, which belong to the 2-oxoglutarate-dependent dioxygenases (2OGD) superfamily that stabilizes collagen during fibrosis. Quantitative polymerase chain reaction analysis demonstrated 2OGD gene expression was increased in CHF samples compared with normal left ventricle (LV) samples. 2OGD gene expression was repressed in angiotensin converting enzyme inhibitor-treated samples. These genes, activated the hydroxylation of proline or lysin residues of procollagen mediated by 2-oxoglutaric acid and O2, produce succinic acid and CO2. Metabolic analysis demonstrated the concentration of succinic acid was significantly increased in CHF samples compared with normal LV samples. Fibrosis was induced in human cardiac fibroblasts by TGF-ß1 treatment. After treatment, the gene and protein expressions of 2OGD, the concentration of succinic acid, and the oxygen consumption rate were increased compared with no treatment. This is the first study to show that collagen-related 2OGD genes contribute to HF during the induction of fibrosis and might be potential therapeutic targets for fibrosis and HF.

The Impact for Medical Management of the Health Information Exchange Through Changes of the Number of the First Visit Patients and Admission Patients in Japan.

Recently Health Information Exchange (HIE) is gradually spreading in Japan. But there are few reports about the effect of the hospital management. So we examined the effect for hospital management through the number of the newly admitted patients from 2013 to 2017. In this study both the total number of the admitted patients who was reserved as first visit patients was higher than not reserved and the number of the admitted patients who visited with introduction letters was higher than without introduction letters. (p < 0.01) The total number of the admitted patients who had been registered to the Ajisai-net was 624 (41.2%) for the same 5 years, and was revealed to be significantly higher than the number of the admitted patients who was reserved first visit with introduction letters. (p < 0.01) In conclusion, use of the Japanese type of the HIE has a potential to increase the newly admitted patients finally.

The Evaluation of the Medical Information Exchange on 24-Hour Operation at North Kyushu Area in Japan.

We report on triage before transportation by sharing patient information between hospitals, making it possible to use the Ajisai-net for 24 hours. Fifty-six times hospital collaboration was conducted during the period from start of hospital cooperation operation until October 2018. Transportation cost reduction of 3,935,000 yen (34,620 dollars) was estimated. It is expected to contribute to improvement of efficiency of emergency medical care in North Kyushu.

[Case of domestically infected hepatitis E with marked thrombocytopenia].

A 52-year-old man was admitted to our hospital for fever, jaundice, and general malaise. Laboratory data revealed elevated serum liver enzyme levels (AST 2377IU/L, ALT 2756IU/L) and bilirubin (T-Bil 3.7 mg/dl). Blood count showed a marked decrease of platelets (2.0 x 10(4)/microl). Serological and virological analysis showed positive results for HEV IgM and HEV RNA, indicating a diagnosis of acute hepatitis E. The serum ferritin level was also markedly elevated (23200 ng/ml). A diagnosis of virus associated hemophagocytic syndrome (VAHS) was strongly suggested. This is the first report of hepatitis E most likely accompanied by VAHS.

Ketone bodies as a predictor of prognosis of hepatocellular carcinoma after transcatheter arterial chemoembolization.

OBJECTIVE: Arterial ketone bodies, which reflect liver function, have been investigated. However, the relationship between venous ketone bodies and hepatocellular carcinoma (HCC) is unclear. We investigated whether prognosis of patients with HCC after transcatheter arterial chemoembolization (TACE) was associated with venous blood ketone bodies. METHODS: Sixty-eight patients with HCC who underwent TACE were recruited for this study. The venous blood ketone body levels were measured 1 d before (pretreatment) and 7 d after TACE (posttreatment). Skeletal muscle quality was evaluated using the intramuscular adipose tissue content (IMAC). RESULTS: Of the 68 patients, 43 (63.2%) were male, with median age of 73.0 y, and the IMAC was -0.274 (range -0.82 to 0.24). The median ketone body levels pre- and posttreatment were 63.0 µmol/L (13-310) and 48.0 µmol/L (8-896), respectively. The cumulative survival rate of patients with total ketone body ratio ([TKBR]: posttreatment/pretreatment total ketone bodies) <1 was 86.6%. The rate with TKBR ≥1 was 59.0% at 300 d (P < 0.05). Cox regression analysis identified the TKBR (≥1, hazard ratio: 2.954, 95% confidence interval [CI]: 1.040-8.390, P = 0.030) that independently and significantly predicted the patients' prognoses. Logistic regression analysis revealed the IMAC (>-0.2745, odds ratio: 3.958, 95% CI: 1.137-13.779, P = 0.031) that predicted TKBR. TKBR and IMAC were positively correlated (rS = 0.358, P = 0.003). CONCLUSIONS: The changes in the venous ketone body were associated with the muscle status and predicted the prognosis of patients with HCC who underwent TACE. The venous ketone bodies could be a new predictor of the prognosis of HCC patients after TACE.

Two cases of hepatopulmonary syndrome with improved liver function following long-term oxygen therapy.

Hepatopulmonary syndrome (HPS) is a complication of liver disease that is characterized by hypoxemia and intrapulmonary vascular dilatations. The only established therapy for this disorder is liver transplantation. Here, we report two patients (a 63-year-old woman and a 72-year-old man) with HPS associated with hepatitis C virus-related cirrhosis. We gave the patients low-dose oxygen supplementation to improve their respiratory symptoms. Surprisingly, their liver function improved from Child Pugh class C to class A, and ascites disappeared after a year of oxygen supplementation. We believe that long-term oxygen therapy contributed to the improvement of liver function in these two cases. Long-term oxygen therapy might offer a new therapeutic approach to improve liver function in patients with cirrhosis with hypoxemia.

Production of single-chain variable fragment antibody (scFv) in fed-batch and continuous culture of Pichia pastoris by two different methanol feeding methods.

This study examined the effects of two methods of methanol feeding, DO-stat and methanol concentration control, in fed-batch and continuous cultures of Pichia pastoris on cell growth and single-chain variable fragment antibody (scFv) expression. By maintaining the methanol concentration at 3.9 g l(-1) in fed-batch culture, a scFv concentration of 198 mg l(-1) was obtained. In continuous culture using both methanol feeding methods, the scFv concentration in the fermentation broth increased with a decreasing dilution rate. A maximum scFv concentration of 810 mg l(-1) at a dilution rate of 0.0094 h(-1) was obtained by maintaining the methanol concentration at 3.9 g l(-1). Although the specific methanol consumption rate was the same for both methods, the specific productivity of scFv was higher in methanol concentration control from 0.0094 to 0.049 h(-1) than it was in DO-stat control. Therefore, continuous culture with methanol feeding by the concentration control method shows promise for the industrial scale production of recombinant proteins by Pichia pastoris.

A New Essential Functions Installed DWH in Hospital Information System: Process Mining Techniques and Natural Language Processing.

Several kinds of event log data produced in daily clinical activities have yet to be used for secure and efficient improvement of hospital activities. Data Warehouse systems in Hospital Information Systems used for the analysis of structured data such as disease, lab-tests, and medications, have also shown efficient outcomes. This article is focused on two kinds of essential functions: process mining using log data and non-structured data analysis via Natural Language Processing.

The Evaluation of the Health Information Exchange with the Number of Usage and the Introduction of Outpatient to the Hospitals at Nagasaki Japan.

Health Information Exchange (HIE) has been gradually spreading in Japan. But the effect and evaluation of these systems have not been proven. The aim of this study is to examine the effect of the Japanese HIE through the evaluation of the clinical activities in Nagasaki University Hospital. The electric medical records of 5335 patients were shared in the Ajisai-net, which was Japanese HIE in Nagasaki, from 2009 to 2015. And the number of shared patients increased every year, and the annual average number was 762.1. On the other hand, the number of the patients who was introduced from clinics to our hospital and whose medical records were shared in the Ajisai-net increased every year. In conclusion, the usage of Japanese HIE is useful for the clinical consultation and medical care, and these systems have the good effect on the hospital management in Japan.

Quality Requirements for Electronic Health Record Systems*. A Japanese-German Information Management Perspective.

BACKGROUND: For more than 30 years, there has been close cooperation between Japanese and German scientists with regard to information systems in health care. Collaboration has been formalized by an agreement between the respective scientific associations. Following this agreement, two joint workshops took place to explore the similarities and differences of electronic health record systems (EHRS) against the background of the two national healthcare systems that share many commonalities. OBJECTIVES: To establish a framework and requirements for the quality of EHRS that may also serve as a basis for comparing different EHRS. METHODS: Donabedian's three dimensions of quality of medical care were adapted to the outcome, process, and structural quality of EHRS and their management. These quality dimensions were proposed before the first workshop of EHRS experts and enriched during the discussions. RESULTS: The Quality Requirements Framework of EHRS (QRF-EHRS) was defined and complemented by requirements for high quality EHRS. The framework integrates three quality dimensions (outcome, process, and structural quality), three layers of information systems (processes and data, applications, and physical tools) and three dimensions of information management (strategic, tactical, and operational information management). CONCLUSIONS: Describing and comparing the quality of EHRS is in fact a multidimensional problem as given by the QRF-EHRS framework. This framework will be utilized to compare Japanese and German EHRS, notably those that were presented at the second workshop.

Increasing hepatitis C virus-associated hepatocellular carcinoma mortality and aging: Long term trends in Japan.

BACKGROUND: The incidence of hepatocellular carcinoma (HCC) in Japan has been increasing. The aim of the study was to determine the epidemiological trends in HCC mortality in Japan. METHODS: We reviewed the medical records of all patients whose death was caused by liver disease between 1981 and 2000 at two hospitals. The courses of death were separated based on presence or absence of HCC when death ensued. Additionally, cohorts of patients with HCC were analyzed in 5-year time periods. RESULTS: The number of deaths from hepatitis C virus (HCV)-associated HCC steadily increased 2.6 times from 49 to 128 during observation period. The mean age at death from HCV-associated HCC from 1996 to 2000 was significantly higher than that in the period from 1981 to 1985 (p<0.0001). INTERPRETATION: Deaths from HCV-associated HCC increased from 1981 to 2000, consistent with the aging of the population in Japan.