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The pathogenic variant (PV) or likely pathogenic variant (LPV) BRCA1/2 gene is strongly associated with hereditary breast or ovarian cancer. Therefore, it is important to screen blood relatives to establish preventive modalities and surveillance. This study evaluated the feasibility of targeted cascade genetic testing for family members of BRCA1/2 gene PV or LPV carriers. We screened 18 families for BRCA1/2 gene status via the conventional cascade genetic test (n = 9) and targeted cascade genetic test (n = 9), which targeted the exon region wherein the index patient showed PV or LPV. The pedigree and clinicopathologic characteristics were reviewed and analyzed. All index patients were diagnosed with breast cancer, while the third family members were all healthy. In the conventional cascade test group, 3 index patients and 3 family members had the BRCA1/2 gene PV or LPV. In the targeted cascade test group, 5 family members had same type of BRCA1/2 gene PV or LPV as their index patients. Two families had an identical string of BRCA1/2 gene PV or LPV. Although the targeted cascade genetic test cannot completely characterize the BRCA1/2 gene, it is sufficient for determining its PV or LPV status. This limited genetic test can be used for family members of PV or LPV carriers.Cause determination is challenging in fever or inflammation of unknown origin (FUO/IUO) despite today's diagnostic modalities. We evaluated the value of F-18 FDG PET/CT in an unselected patient collective. This retrospective nonrandomized single-center study enrolled 300 male and female patients with FUO/IUO. PET/CT findings were compared with final clinical outcomes to determine the sensitivity, specificity, clinical significance, etiological distribution of final diagnoses, impact on treatment, role of white-blood cell count (WBC), and C-reactive protein (CRP). In 54.0% (162/300) PET/CT was the decisive exanimation for establishing the final diagnosis, in 13.3% (40/300) the findings were equivocal and indecisive, in 3.3% (10/300) PET/CT findings were false positive, while in 29.3% (88/300) a normal F-18 FDG pattern was present. Statistical analysis showed a sensitivity of 80.2% and a specificity of 89.8% for the contribution of PET/CT to the final diagnosis. CRP levels and WBC were not associated with PET/CT outcome. PET/CT let to new treatment in 24.0% (72/300), treatment change in 18.0% (54/300), no treatment change in 49.6% (149/300), and in 8.3% (25/300) no data was available. Our study demonstrates the utility of F-18 FDG PET/CT for source finding in FUO/IUO if other diagnostic tools fail.Oncogenic protein E6 from Human Papilloma Virus 16 (HPV-16) mediates the degradation of Membrane-associated guanylate kinase with inverted domain structure-1 (MAGI-1), throughout the interaction of its protein binding motif (PBM) with the Discs-large homologous regions 1 (PDZ1) domain of MAG1-1. Generic variation in the E6 gene that translates to changes in the protein's amino acidic sequence modifies the interaction of E6 with the cellular protein MAGI-1. MAGI-1 is a scaffolding protein found at tight junctions of epithelial cells, where it interacts with a variety of proteins regulating signaling pathways. MAGI-1 is a multidomain protein containing two WW (rsp-domain-9), one guanylate kinase-like, and six PDZ domains. PDZ domains played an important role in the function of MAGI-1 and served as targets for several viral proteins including the HPV-16 E6. The aim of this work was to evaluate, with an in silico approach, employing molecular dynamics simulation and protein-protein docking, the interaction of the intragenic variants E-G350 (L83V), E-C188/G350 (E29Q/L83V), E-A176/G350 (D25N/L83V), E6-AAa (Q14H/H78Y/83V) y E6-AAc (Q14H/I27RH78Y/L83V) and E6-reference of HPV-16 with MAGI-1. We found that variants E-G350, E-C188/G350, E-A176/G350, AAa and AAc increase their affinity to our two models of MAGI-1 compared to E6-reference.This study aimed to verify the effects of congested fixture and matches' participation on internal and external workload indexes in professional Brazilian soccer players. Rate of perceived exertion-based training load (sRPE), distance- and accelerometry-based measures were daily monitored over 119 training sessions and 33 matches performed by 29 male outfield players. Weeks were classified as congested (n = 11, two or more matches within a 7-day period) and regular (n = 10, one match or less within a 7-day period). The players were divided based on the matches' participation (1) players who played ≥ 60 min (G1); (2) players who played  less then  60 min (G2); (3) players who did not participate of the match (G3). The findings showed that independent of the levels of participation during the matches, regular weeks presented greater acute, monotony, and strain indices for internal and external workload measures than congested weeks. The G1 presented the highest values for most of the workload indices in both regular and congested weeks, except for monotony indices (internal and external load) that G2 showed greater values than G1 and G3. Coaches and practitioners should plan the training "doses" to reduce disparities of these different match's participation and congested schedule weeks.Worldwide, communities are facing increasing flood risk, due to more frequent and intense hazards and rising exposure through more people living along coastlines and in flood plains. Nature-based Solutions (NbS), such as mangroves, and riparian forests, offer huge potential for adaptation and risk reduction. The capacity of trees and forests to attenuate waves and mitigate storm damages receives massive attention, especially after extreme storm events. However, application of forests in flood mitigation strategies remains limited to date, due to lack of real-scale measurements on the performance under extreme conditions. Experiments executed in a large-scale flume with a willow forest to dissipate waves show that trees are hardly damaged and strongly reduce wave and run-up heights, even when maximum wave heights are up to 2.5 m. It was observed for the first time that the surface area of the tree canopy is most relevant for wave attenuation and that the very flexible leaves limitedly add to effectiveness. Overall, the study shows that forests can play a significant role in reducing wave heights and run-up under extreme conditions. Currently, this potential is hardly used but may offer future benefits in achieving more adaptive levee designs.The human gut contains a complex microbiota dominated by bacteriophages but also containing other viruses and bacteria and fungi. There are a growing number of techniques for the extraction, sequencing, and analysis of the virome but currently no standardized protocols. This study established an effective workflow for virome analysis to investigate the virome of stool samples from two understudied ethnic groups from Malaysia the Jakun and Jehai Orang Asli. By using the virome extraction and analysis workflow with the Oxford Nanopore Technology, long-read sequencing successfully captured close to full-length viral genomes. The virome composition of the two indigenous Malaysian communities were remarkably different from those found in other parts of the world. Additionally, plant viruses found in the viromes of these individuals were attributed to traditional food-seeking methods. This study establishes a human gut virome workflow and extends insights into the healthy human gut virome, laying the groundwork for comparative studies.Sodium-glucose cotransporter 2 inhibitor (SGLT2i) treatment is a therapeutic approach for type 2 diabetes mellitus (T2DM). Some reports have shown that SGLT2i treatment improves insulin resistance; however, few studies have evaluated insulin resistance by the glucose clamp method. Hepatic insulin clearance (HIC) is a new pathophysiological mechanism of T2DM. The effect of SGLT2i treatment on hepatic insulin clearance and insulin resistance is not well known. We investigated the effect of SGLT2i treatment on insulin resistance, insulin secretion, incretin levels, body composition, and hepatic insulin clearance. We conducted a meal tolerance test (MTT) and a hyperinsulinemic-euglycemic clamp test in 9 T2DM patients. Ipragliflozin (50 mg/day) was administered, and the MTT and clamp test were performed after 4 months. We calculated HIC as the postprandial C-peptide AUC-to-insulin AUC ratio. We also measured GLP-1, GIP, and glucagon levels during the MTT. Body weight and HbA1c were decreased, although not significantly, after 4 months of treatment. Postprandial glucose, fasting insulin and postprandial insulin were significantly decreased. Insulin resistance with the glucose clamp was not changed, but the HOMA-IR and insulin sensitivity indices were significantly improved. Incretin and glucagon levels were not changed. Hepatic insulin clearance was significantly increased, but whole-body insulin clearance was not changed. [https://www.selleckchem.com/products/nsc-663284.html NSC 663284] The FIB-4 index and fatty liver index were significantly reduced. The HOMA-beta and insulinogenic indices were not changed, but the C-peptide index was significantly increased. Although the number of patients was small, these results suggested that SGLT2i treatment improved liver function, decreased hepatic insulin resistance, and increased hepatic insulin clearance, despite the small weight reduction.The development of simple and safe methods for recovering environmental pollutants, such as heavy metals, is needed for sustainable environmental management. Short elastin-like peptide (ELP) analogues conjugated with metal chelating agents are considered to be useful as metal sequestering agents as they are readily produced, environment friendly, and the metal binding domain can be selected based on any target metal of interest. Due to the temperature dependent self-assembly of ELP, the peptide-based sequestering agents can be transformed from the solution state into the particles that chelate metal ions, which can then be collected as precipitates. In this study, we developed a peptide-based sequestering agent, AADAAC-(FPGVG)4, by introducing the metal-binding sequence AADAAC on the N-terminus of a short ELP, (FPGVG)4. In turbidity measurements, AADAAC-(FPGVG)4 revealed strong self-assembling ability in the presence of metal ions such as Cd2+ and Zn2+. The results from colorimetric analysis indicated that AADAAC-(FPGVG)4 could capture Cd2+ and Zn2+. Furthermore, AADAAC-(FPGVG)4 that bound to metal ions could be readily recycled by treatment with acidic solution without compromising its metal binding affinity. The present study indicates that the fusion of the metal-binding sequence and ELP is a useful and powerful strategy to develop cost-effective heavy metal scavenging agents with low environmental impacts.Carbon ion radiotherapy (CIRT) has garnered interest for the treatment of locoregional rectal cancer recurrence. No study has compared CIRT and X-ray radiotherapy (XRT) for reirradiation (reRT) in such cases. We analyzed and compared the clinical outcomes such as local control, overall survival, and late toxicity rate between CIRT and XRT, for treating locoregional rectal cancer recurrence. Patients with rectal cancer who received reRT to the pelvis by CIRT or XRT from March 2005 to July 2019 were included. The CIRT treatment schedule was 70.4 Gy (relative biological effectiveness) in 16 fractions. For the XRT group, the median reRT dose was 50 Gy (range 25-62.5 Gy) with a median of 25 fractions (range 3-33). Thirty-five and 31 patients received CIRT and XRT, respectively. Tumour and treatment characteristics such as recurrence location and chemotherapy treatment differed between the two groups. CIRT showed better control of local recurrence (adjusted hazard ratio [HR] 0.17; p = 0.002), better overall survival (HR 0.