In this paper, we describe the first stereocontrolled synthesis and properties of boranophosphate DNA (PB-DNA), which contains all of the four nucleobases longer than 10mer. Synthesis was ...accomplished via an oxazaphospholidine approach combined with acid-labile protecting groups on nucleobases. It was demonstrated that there were significant differences between all-(Rp)- and all-(Sp)-PB-DNA in terms of the duplex-formation ability, nuclease resistance, and ribonuclease H (RNase H) activity. In particular, all-(Sp)-PB-DNA was demonstrated to show a duplex-formation ability with RNA and RNase H activity, both of which are necessary for antisense-type nucleic acid therapeutics.
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IJS, KILJ, NUK, PNG, UL, UM
Abstract
No previous study has ever explored the association between coastal exposure and the mental health of residents in a post-disaster context. Therefore, we aimed to confirm whether there was ...an association between sea visibility and coastal proximity and the mental health of coastal residents a devastating tsunami. We targeted 15 coastal municipalities located in the Miyagi Prefecture, and obtained data from a community-based cohort study. The baseline survey was initiated 2 years after the 2011 Great East Japan Earthquake and Tsunami and the secondary survey was initiated 6 years after the disaster. We applied multilevel mixed-effects models to the longitudinal data. Our outcome measure was the Kessler Psychological Distress Scale (K6) score. We assessed the data collected from 2,327 respondents on both surveys as of April 2018 for this ongoing cohort study. We found that neither sea visibility nor coastal proximity was significantly associated with the recovery of mental health after the disaster. However, we found a distinctive trend of mental health recovery in people who lived alone with a sea view, indicating that visibility of the sea had a negative effect on their mental health immediately after the GEJET, but that the negative effect was subsequently eliminated.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
It has been pointed out that eye-level greenery streetscape promotes leisure walking which is known to be a health -positive physical activity. Most previous studies have focused on the total amount ...of greenery in the eye-level streetscape to investigate its association with walking behaviour. While it is acknowledged that taller trees contribute to greener environments, providing enhanced physical and psychological comfort compared to lawns and shrubs, the examination of streetscape metrics specifically focused on greenery height remains largely unexplored. Therefore, this study examined the relationship between objective indicators of street greenery categorized by height from a pedestrian viewpoint and leisure walking time. We created streetscape indices of street greenery using Google Street View Images at 50-m intervals in an urban area in Sendai City, Japan. The indices were classified into four ranges according to the latitude of the virtual hemisphere centred on the viewer. We then investigated their relationship to self-reported leisure walking. Positive associations were identified between the street greenery in higher positions and leisure walking time, while there was no significant association between the greenery in lower positions. The findings indicated that streets with rich greenery in high positions may promote residents' leisure walking, indicating that greenery in higher positions contributes to thermally comfortable and aesthetic streetscapes, thus promoting leisure walking. Increasing the amount of greenery in higher positions may encourage residents to increase the time spent leisure walking.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
To evaluate the utility and safety of a short-type double-balloon endoscope (DBE) in the treatment of biliary disease in patients with surgically altered gastrointestinal (GI) anatomy.
This study was ...conducted as a multicenter, single-arm, prospective trial at five tertiary academic care centers and three community-based hospitals in Japan. Consecutive patients with biliary disease with altered GI anatomy were prospectively included in this study.
A total of 311 patients underwent double-balloon endoscopic retrograde cholangiography (ERC). The success rate of reaching the target site, the primary end point, was 97.7% (95% confidence interval (CI): 95.4-99.1). The success rate of biliary cannulation and contrast injection of the targeted duct, the secondary end point, was 96.4% (95% CI: 93.6-98.2), and the therapeutic success rate was 97.9% (95% CI: 95.4-99.2). Adverse events occurred in 33 patients (10.6%, 95% CI: 7.1-14.0) and were managed conservatively in all patients with the exception of 1 in whom a perforation developed, requiring emergency surgery.
ERC using a short-type DBE resulted in an excellent therapeutic success rate and a low rate of adverse events. This treatment can be a first-line treatment for biliary disease in patients with surgically altered GI anatomy.
8540 Background: Immune checkpoint inhibitor plus platinum-containing chemotherapy is the standard of care for patients with advanced non-small cell lung cancer (NSCLC). Pembrolizumab combined with ...pemetrexed and cisplatin/carboplatin is approved as first line treatment for patients with metastatic non-squamous NSCLC based on the results of KEYNOTE-189. However, data on the efficacy and safety of this regimen are limited for patients aged ≥75 years. In preclinical models, anti-PD-L1 antibody with pemetrexed enhanced the antitumor effect more than the combination of pemetrexed with carboplatin. These results suggest that pembrolizumab plus pemetrexed can be effective while potentially sparing severe side effects by omitting carboplatin. Methods: This multicenter, open-label, phase 2 trial was conducted at 42 institutions in Japan to evaluate the efficacy and safety of pemetrexed plus pembrolizumab. Eligible patients had metastatic/recurrent non-squamous NSCLC without sensitizing EGFR or ALK mutations, were aged ≥75 years, had a PD-L1 TPS of less than 50%, had received no prior systemic chemotherapy, and had an ECOG performance status of 0 or 1. Patients received pemetrexed (500 mg/m 2 ) plus pembrolizumab (200 mg/body) on day 1 of each 21-day cycle. Treatment continued until radiographic progression or unacceptable toxicity was observed. The primary endpoint was the objective response rate (ORR). Secondary endpoints included progression-free survival (PFS), overall survival (OS), and safety. This trial is registered with ClinicalTrials.gov (NCT04396457) and the Japan Registry of Clinical Trials (jRCTs041200012). Results: From July 2020 to May 2022, 49 patients were enrolled in this study. The median follow-up time was 15.4 months. The median age was 79.0 years (range 75-91), 77.6% of the patients were male, and 57.1% had a PD-L1 TPS ≥1%. The ORR was 36.7% (95% CI 23.4-51.7), and the disease control rate was 65.3% (95% CI 50.4-78.3%). The median PFS was 7.6 months (95% CI 4.8-16.2), and the median OS was 19.4 months (95% CI 11.8- not reached). The most common grade 3 or 4 adverse events were neutropenia (31.3%), leukopenia (20.8%), and anemia (12.5%). Serious adverse events were observed in 14 patients (4 with pneumonitis, 2 with decreased appetite, 2 with febrile neutropenia). No treatment-related deaths were observed. Conclusions: Pembrolizumab plus pemetrexed demonstrated an ORR of 36.7% and met the primary endpoint. The safety profile was tolerable and manageable. This combination therapy is a promising candidate as a novel first line treatment strategy for older patients with metastatic non-squamous NSCLC. Clinical trial information: NCT04396457 .
Background
Pectus excavatum is the most common congenital deformity of the chest, with a frequency of one in 300 to 500 births. Twenty-five percent of pectus excavatum patients are female. Different ...surgical methods are used to treat female patients, depending on the degree of their thorax’s deformity. For patients with mild deformity, fat transfer alone is often used to augment their breasts and improve appearance. This study aims to evaluate the thickness of the subdermal fat of adult female patients with pectus excavatum.
Methods
The thickness of subdermal fat of the central regions of the chest was measured by referring to computer tomographic data of 62 adult Japanese female patients with pectus excavatum and 64 intact Japanese adult females. The pectus excavatum patients have no other comorbidities. These two groups were defined as pectus group and intact group, respectively. The two groups showed no statistically significant differences in ages, BMI, and thoracic cage width. Fat thickness was measured for each person at the levels of the clavicle, middle-height of the sternum, nipples, and inframammary fold. The data for each level were compared between the two groups.
Results
Fat thickness presented statistically significant differences at the levels of nipples and inframammary fold between pectus group (17.8 ± 5.2 SD mm at the nipple level; 19.2 ± 4.9 SD mm at the inframammary fold level) and intact group (8.0 ± 2.6 SD mm at the nipple level; 10.2 ± 4.3SD mm at the inframammary fold level). Fat thickness presented no statistically significant differences between the two groups at the levels of clavicle and middle-height of the sternum.
Conclusions
The intramammary fat of female pectus excavatum patients is thicker than that of intact adult women. Because of the thick fat, the intramammary groove can appear shallow after the depressed sternum is elevated in the correction surgery for pectus excavatum. Accordingly, the breasts can look smaller. Removal or positional transfer of intramammary fat can remedy this esthetic complication.
Level of evidence: Level III, diagnostic study.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
We investigated the differences in the prevalence of ulnar nerve instability (UNI) by hand dominance and evaluated the relationship between UNI and morphologic changes in the ulnar nerve and the ...clinical findings and upper limb function.
This study examined 153 healthy participants (n = 306 elbows; 44 men, 112 women; mean age 65.4 years) who underwent ultrasonography to assess the ulnar nerve cross-sectional area (UNCSA) at three points of the bilateral cubital tunnel at 30° of elbow flexion. Participants were divided into three groups based on the ultrasonography findings of UNI: no instability (type N), subluxation (type S), and dislocation (type D). For the dominant and nondominant sides, we assessed the relationship between the UNCSA and clinical factors, including the age, gender, height, weight, body mass index, fat mass, grip strength, key pinch strength, UNCSA, and Patient-Rated Elbow Evaluation score.
We identified 75 cases without instability in both elbows and 78 cases with some instability. The prevalence of UNI was 51%. No significant difference was found between hand dominance and the prevalence of UNI. The UNCSA at 1 cm proximal to the medial epicondyle on the bilateral sides in type S was the most increased among three types.
UNI was identified in almost half of the participants, with no marked difference found in the hand dominance. The UNCSA at 1 cm proximal to the medial epicondyle was significantly increased the most in type S. UNI does not appear to be associated with elbow symptoms in the general population.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Several pre-clinical and clinical studies suggest a potential predictive role of epidermal growth factor receptor (EGFR) mutation in responsiveness to cytotoxic chemotherapy. The aim of this phase II ...study was to evaluate the efficacy and safety of pemetrexed-carboplatin combination as first-line chemotherapy in advanced non-squamous non-small cell lung cancer (NSCLC) limited to EGFR-wild-type cases.
In this single-arm, multicenter clinical trial, patients received pemetrexed (500 mg/m(2)) and carboplatin (area under the curve=6) intravenously on day 1 every 3 weeks for three to six cycles. The objective response rate (ORR) was the primary end-point; secondary end-points included the disease control rate (DCR), progression-free survival (PFS), overall survival (OS) and safety.
A total of 54 patients were enrolled and 53 patients received therapy. No complete response was observed and partial response was observed in 19 (35.8%) cases, resulting in an ORR of 35.8% 95% confidence interval (CI)=23.1-50.2%. Stable disease was observed in 20 (37.7%) patients and therefore the DCR was 73.6% (95% CI=59.7-84.7%). The median PFS was 5.4 months (95% CI=4.1-6.8 months) and the median OS was 12.7 months (95% CI=9.3-16.1 months). Treatment-related grade 3 or 4 hematological toxicities were neutropenia, leukopenia, anemia and thrombocytopenia in 35.8%, 11.3%, 30.2%, and 32.1% of patients, respectively. No grade 3 febrile neutropenia was observed, and grade 3 or 4 non-hematological toxicities were mild. There was no treatment-related death.
The pemetrexed-carboplatin combination was effective and well-tolerated in patients with EGFR-wild-type non-squamous NSCLC (UMIN-CTR number: UMIN000003393).
Stage IV symptomatic cervical metastasis is accompanied by progressing neurologic symptoms and neck pain. Typically, the goal of the treatment of this type of cancer is to improve the quality of life ...(QOL) of the patient. Indeed, function recovery is achieved by timely surgical treatment and radiosurgery that delivers high doses of radiation with very high accuracy. Here, we describe a case of symptomatic cervical metastasis that was treated by our multidisciplinary approach, which is imperative to restore the activities of daily living (ADL) of patients and improve their QOL. A 72-year-old man presented with paralysis of the left arm and neck pain that were caused by cervical metastasis of hepatocellular cancer. The patient was treated with an emergency tumor resection that was followed by posterior cervical spinal fusion. Beginning the next day, acute rehabilitation was provided, and the patient was able to perform ADLs. After three postoperative weeks, he returned home from the hospital. Fractionated radiation using Cyberknife was then administered for 4 days as adjuvant stereotactic radiosurgery. Three months after the first round of radiation treatment, cervical metastasis with muscular weakness of the right arm and pain emerged outside the irradiated field. Thus, fractionated radiosurgery was administered for 4 more days. After 13 months, thoracic spinal metastasis was identified, and the pain was treated with standard external-beam radiotherapy. These treatments resolved the symptoms and pain, and the patient has been able to perform ADLs at his home for more than 18 months. Restoration of daily activity that was decreased by symptomatic cervical metastasis was essential for improving the QOL of the patient. Considering the poor prognosis of the patient due to the disease progression, it was critical to perform prompt diagnosis, ensure appropriate treatment, and reduce the duration of therapy. Therefore, the results of this report suggest the importance of multidisciplinary team-oriented medicine, including emergency surgery, high-dose radiation with extreme accuracy, focused rehabilitation, coordinated home care, and comprehensive postoperative consultation.
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