Although previous reports have shown that sodium-glucose cotransporter-2 (SGLT2) inhibitors have a blood pressure (BP) lowering effect, relevant long-term data is limited. This study aimed to ...evaluate the effect of the SGLT2 inhibitor ipragliflozin on BP, and associations between BP reduction and changes in cardiometabolic variables in diabetic patients. This was a sub-analysis of the PROTECT trial, a multicenter, randomized, open-label study to assess if ipragliflozin delays carotid atherosclerosis in patients with type 2 diabetes. Participants were randomized to ipragliflozin and control groups. The primary endpoint of the present sub-analysis was the trajectory of systolic BP over 24 months. Correlations between systolic BP changes and cardiometabolic variables were also evaluated. A total of 232 eligible participants with well-balanced baseline characteristics were included in each study group. Throughout the 24-month study period, mean systolic BP was lower in the ipragliflozin group. At 24 months, a between-group difference (ipragliflozin minus control) in mean systolic BP change from baseline was -3.6 mmHg (95% confidence interval, -6.2 to -1.0 mmHg), and the reduction in systolic BP in the ipragliflozin group was consistent across subgroups examined. Changes in systolic BP significantly correlated with those in body mass index in the ipragliflozin group, while no significant correlations with other cardiometabolic variables tested were observed. In conclusion, ipragliflozin treatment was associated with BP reduction throughout the 24-month follow-up period as compared to control treatment. BP reduction correlated with weight loss, which might be one of the mechanisms for the BP lowering effect of SGLT2 inhibitors.
Background
The Response Evaluation Criteria in Solid Tumors (RECIST) for computed tomography (CT) is preoperatively used to evaluate therapeutic effects. However, it does not reflect the pathological ...treatment response (PTR) of pancreatic ductal adenocarcinoma (PDAC). The Positron Emission Tomography Response Criteria in Solid Tumors (PERCIST) for positron emission tomography (PET)/CT is effective in other cancers. This study aimed to confirm the usefulness of PERCIST and the prognostic utility of PET/CT for PDAC.
Methods
Forty‐two consecutive patients with PDAC who underwent neoadjuvant therapy (NAT) and pancreatectomy at our institution between 2014 and 2018 were retrospectively analyzed. We evaluated the treatment response and prognostic significance of PET/CT parameters and other clinicopathological factors.
Results
Twenty‐two patients who underwent PET/CT both before and after NAT with the same protocol were included. RECIST revealed stable disease and partial response in 20 and 2 cases, respectively. PERCIST revealed stable metabolic disease, partial metabolic response, and complete metabolic response in 8, 9, and 5 cases, respectively. The PTR was G3, G2, and G1 in 8, 12, and 2 cases, respectively. For comparing the concordance rates between PTR and each parameter, PERCIST (72.7% 16/22) was significantly superior to RECIST (36.4% 8/22) (P = .017). The area under the curve survival values of PET/CT parameters were 0.777 for metabolic tumor volume (MTV), 0.500 for maximum standardized uptake value, 0.554 for peak standardized uptake value corrected for lean body mass, and 0.634 for total lesion glycolysis. A 50% cut‐off value for the MTV reduction rate yielded the largest difference in survival between responders and nonresponders. On multivariate analysis, MTV reduction rates < 50% were independent predictors for relapse‐free survival (hazard ratio HR, 3.92; P = .044) and overall survival (HR, 14.08; P = .023).
Conclusions
PERCIST was more accurate in determining NAT’s therapeutic effects for PDAC than RECIST. MTV reduction rates were independent prognostic factors for PDAC.
18F‐fluorodeoxyglucose positron emission tomography/computed tomography (PET/CT) was more accurate in determining the therapeutic effects of neoadjuvant therapy for pancreatic ductal adenocarcinoma than CT, which detects anatomical changes. The reduction rate of the PET/CT parameter was an independent prognostic factor for pancreatic ductal adenocarcinoma.
Stress‐activated protein kinase/c‐Jun N‐terminal kinase (SAPK/JNK) responds to a variety of stress stimuli and controls cell fates such as cell cycle entrance, apoptosis and senescence. Stimuli such ...as ultraviolet irradiation and chemical reagents that damage genomic DNA induce the activation of the SAPK/JNK signaling pathway. However, it is unclear how the signal arising in the nucleus owing to DNA damage is transmitted to SAPK/JNK in the cytoplasm. Here, we report that the nuclear components Daxx and Ras‐association domain family 1C (RASSF1C) link DNA damage to SAPK/JNK activation in HeLa cells. In response to DNA damage, Daxx localized in promyelocytic leukaemia‐nuclear bodies (PML‐NBs) undergoes ubiquitination and degradation. RASSF1C, a tumor suppressor and newly identified binding partner of Daxx, is constitutively anchored by Daxx in PML‐NBs but is released from the nucleus when Daxx is degraded. This released RASSF1C translocates to cytoplasmic microtubules and participates in the activation of SAPK/JNK. Our data define a novel mechanism by which the Daxx–RASSF1C complex in PML‐NBs couples nuclear DNA damage to the cytoplasmic SAPK/JNK signaling pathway.
In this demonstration, we present FACTUS, a tag-based Twitter user search system using Twitter lists. FACTUS provides a faceted search over Twitter users. To this end, the system first extracts tags, ...such as “music” and “sports,” from Twitter lists, and assigns the tags to Twitter users. Then, facets are computed based on the tags, thereby enabling us to browse Twitter users using facets.
Scapulothoracic dissociation (STD) is a rare entity characterized by shoulder girdle and neurovascular disruption. It is not widely recognized in Japan even though it is a life-threatening injury. ...We report a case of multiple open fractures of the extremities associated with STD. A woman in her 40s presented with a head injury, multiple open fractures of the extremities, and right subclavian artery and vein disruption after being injured in a traffic accident. The patient underwent subclavian artery and vein ligation for the management of hemorrhagic shock. She received multidisciplinary treatment for multi-organ dysfunction and underwent surgery for fractures ; however, necrosis of the soft tissue of the right hand necessitated amputation of the upper arm. STD may lead to hemorrhagic shock ; physicians should rapidly establish a strategy for hemostasis, evaluate functional disorders, and make decisions regarding limb sparing for earlier recovery of the patient’s condition.
Patients with pruritus receiving hemodialysis frequently experience oppressive physical and psychiatric symptoms that directly affect their quality of life and increase mortality. However, treatment ...options are limited.
To determine the clinically recommended dose of difelikefalin, a κ-opioid receptor agonist, based on the efficacy, dose response, safety, and pharmacokinetics.
This randomized, double-blind, placebo-controlled, 4-arm phase 2 trial was conducted from February 1, 2019, to October 22, 2019, at 94 sites in Japan. Patients with moderate to severe pruritus receiving hemodialysis were enrolled.
Difelikefalin (0.25, 0.5, and 1.0 μg/kg) and placebo were intravenously administered 3 times a week at the end of each hemodialysis session for 8 weeks.
The primary end point was the change from baseline in the weekly mean Worst Itching Intensity Numerical Rating Scale (NRS) score at week 8. Secondary outcomes measured changes in itch-related quality-of-life score using the Skindex-16 and 5-D itch scale. Safety was assessed according to adverse events, laboratory tests, vital signs, body weight, and 12-lead electrocardiogram.
A total of 247 Japanese patients (186 male 75%; mean SD age, 64.5 11.7 years) were randomized to placebo (n = 63), 0.25 μg/kg of difelikefalin (n = 61), 0.5 μg/kg of difelikefalin (n = 61), or 1.0 μg/kg of difelikefalin (n = 62). The changes from baseline in the adjusted mean (SE) of the 24-hour Worst Itching Intensity NRS score at week 8 were -2.86 (0.29) in the placebo group, -2.97 (0.29) in the 0.25 μg/kg of difelikefalin group, -3.65 (0.30) in the 0.5 μg/kg of difelikefalin group, and -3.64 (0.30) in the 1.0 μg/kg of difelikefalin group. Significant differences were found in the 0.5 μg/kg of difelikefalin group (adjusted mean difference, -0.80; 95% CI, -1.55 to -0.04; P = .04) and the 1.0 μg/kg of difelikefalin group (adjusted mean difference, -0.78; 95% CI, -1.54 to -0.03; P = .04) compared with placebo. The Skindex-16 overall score and 5-D itch scale total score indicated an improvement with treatment with 0.5 and 1.0 μg/kg of difelikefalin (adjusted weekly mean SE Skindex-16 overall score at week 8, -27.79 2.05; 95% CI, -31.83 to -23.74 for 0.5 μg/kg of difelikefalin and -22.69 2.04; 95% CI, -26.71 to -18.68 for 1.0 μg/kg of difelikefalin; adjusted weekly mean SE 5-D itch scale total score at week 8, -6.5 0.4; 95% CI, -7.2 to -5.8 for 0.5 μg/kg of difelikefalin and -6.8 0.3; 95% CI, -7.5 to -6.2 for 1.0 μg/kg of difelikefalin). The incidence of adverse events was 67% (42 of 63 patients) in the placebo group, 72% (44 of 61 patients) in the 0.25 μg/kg of difelikefalin group, 77% (47 of 61 patients) in the 0.5 μg/kg of difelikefalin group, and 85% (53 of 62 patients) in the 1.0 μg/kg of difelikefalin group. No dependency was reported.
The findings of this phase 2 randomized clinical trial of difelikefalin suggest that 0.5 μg/kg of difelikefalin should be the clinically recommended dose as a new option for treating moderate to severe pruritus in patients undergoing hemodialysis because of its efficacy, acceptable tolerability, and manageable safety profile.
ClinicalTrials.gov Identifier: NCT03802617.
A number of nuclear complexes modify chromatin structure and operate as functional units. However, the in vivo role of each component within the complexes is not known. ATP-dependent chromatin ...remodeling complexes form several types of protein complexes, which reorganize chromatin structure cooperatively with histone modifiers. Williams syndrome transcription factor (WSTF) was biochemically identified as a major subunit, along with 2 distinct complexes: WINAC, a SWI/SNF-type complex, and WICH, an ISWI-type complex. Here, WSTF⁻/⁻ mice were generated to investigate its function in chromatin remodeling in vivo. Loss of WSTF expression resulted in neonatal lethality, and all WSTF⁻/⁻ neonates and almost equal to10% of WSTF⁺/⁻ neonates suffered cardiovascular abnormalities resembling those found in autosomal-dominant Williams syndrome patients. Developmental analysis of WSTF⁻/⁻ embryos revealed that Gja5 gene regulation is aberrant from E9.5, conceivably because of inappropriate chromatin reorganization around the promoter regions where essential cardiac transcription factors are recruited. In vitro analysis in WSTF⁻/⁻ mouse embryonic fibroblast (MEF) cells also showed impaired transactivation functions of cardiac transcription activators on the Gja5 promoter, but the effects were reversed by overexpression of WINAC components. Likewise in WSTF⁻/⁻ MEF cells, recruitment of Snf2h, an ISWI ATPase, to PCNA and cell survival after DNA damage were both defective, but were ameliorated by overexpression of WICH components. Thus, the present study provides evidence that WSTF is shared and is a functionally indispensable subunit of the WICH complex for DNA repair and the WINAC complex for transcriptional control.
Abstract Background and aims Disruption of atherosclerotic plaque and distal embolism often cause peri-procedural myocardial injury during percutaneous coronary intervention (PCI). In the present ...study, we evaluate the association between the characteristics of the target lesion and the amount of debris captured by the filter-type distal protection device. Methods We enrolled 120 consecutive patients with acute coronary syndrome, who underwent coronary stent implantation with a filter-type distal protection device after integrated backscatter intravascular ultrasound (IB-IVUS) analysis. The amount of debris captured by the protection filter was measured through microscopic evaluation. Results The lipid and fibrous volume evaluated with IB-IVUS was significantly correlated with the amount of the captured debris (r = 0.657, p < 0.01), (r = 0.322, p < 0.01). The lipid plaque fraction showed a positive correlation (r = 0.335, p < 0.01), while the fibrous plaque fraction was found to be inversely correlated (r = −0.375, p < 0.01) with the amount of captured debris. Multivariate regression analysis showed that lipid volume correlated independently with the amount of captured debris. Conclusion The volume of the lipid-rich plaque was associated with the amount of procedure-related debris released and captured by the filter-type distal protection device.
H-SPOOL Komamizu, Takahiro; Amagasa, Toshiyuki; Kitagawa, Hiroyuki
International journal of Web information systems,
08/2016, Letnik:
12, Številka:
3
Journal Article
Recenzirano
PurposeLinked data (LD) has promoted publishing information, and links published information. There are increasing number of LD datasets containing numerical data such as statistics. For this reason, ...analyzing numerical facts on LD has attracted attentions from diverse domains. This paper aims to support analytical processing for LD data.Design/methodology/approachThis paper proposes a framework called H-SPOOL which provides series of SPARQL (SPARQL Protocol and RDF Query Language) queries extracting objects and attributes from LD data sets, converts them into star/snowflake schemas and materializes relevant triples as fact and dimension tables for online analytical processing (OLAP).FindingsThe applicability of H-SPOOL is evaluated using exiting LD data sets on the Web, and H-SPOOL successfully processes the LD data sets to ETL (Extract, Transform, and Load) for OLAP. Besides, experiments show that H-SPOOL reduces the number of downloaded triples comparing with existing approach.Originality/valueH-SPOOL is the first work for extracting OLAP-related information from SPARQL endpoints, and H-SPOOL drastically reduces the amount of downloaded triples.
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