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AbstractObjective To compare the cumulative impact of sequential wear on mechanical properties and appearance of a composite resin (CR), Filtek Z250®, a glass ionomer GI, Fuji IX GP®, and a glass hybrid (GH), Equia Forte®.Material and Methods Six equally sized specimens of each material were subjected to wear tests, i.e., simulation of brushing, chewing and acidic liquid exposure, mimicking at least 6 months of clinical exposure. Surface roughness, hardness, substance loss and degree of shade lightness were determined.Results Following wear tests, significant increase in surface roughness and decrease in hardness values were observed for all materials (p < .05). Significantly larger substance loss was found in Equia Forte® specimens compared to Filtek Z250® (p < .05), while that of Fuji IX® exceeded the measurement capacity of the instrument. Opposite to the two other materials, the shade of Filtek Z250® became darker.Conclusions Sequential wear exposure mimicking abrasion, erosion and attrition to products representing CR, GI and GH, caused weakening and change in appearance of the materials. The composite resin was the most mechanically resistant to the sequential wear.

Abstract Introduction Flash glucose monitor (FGM) use is increasing. A set of Danish criteria for regulating the use has been released. We assessed their validity. Methods Patients with type 1 diabetes attending our clinic were offered Freestyle Libre Sensor for 12 months and stratified into fulfilling the Danish regional criteria (RC+) or not (RC−). Primary endpoint was achieving individualized target HbA1c. Secondary endpoints were HbA1c reduction ≥5%, time in range (TIR), time below range (TBR), daily scans, change in median HbA1c, and noted experiences. Results Two hundred seventy‐eight participants were included. Forty‐four participants met target HbA1c after 1 year. No difference between RC+ and RC− was observed (p = .136). Higher age was associated with probability to meet target HbA1c (RR = 3.15, [95% CI: 1.15, 8.62]) as was frequent scans (RR = 1.88, [95% CI: 0.99, 3.57]). One hundred twenty‐three participants met an HbA1c reduction ≥5%, the majority represented in RC+ (p = .023). Higher baseline HbA1c was associated with a reduction of HbA1c ≥5% after 1 year (RR = 1.97, [95% CI: 1.40, 2.78]). There was no difference between RC+ and RC− in TIR, TBR, and daily scans. Positive experiences dominated from both participants and healthcare professionals. More positive experiences were noted from healthcare professionals in RC− (p = .003) but no difference in reported experiences among participants in RC+ and RC− (p = .880). Conclusion The Danish Regional Criteria seems not a valid tool for regulation of FGM. Participants of older age and participants with more frequent daily scans might benefit more from FGM.

Background and aimsGlucagon-like peptide 1 (GLP-1) receptor agonists (GLP-1RA) are widely used for the treatment of type 2 diabetes, and recent studies indicate that they may be cardio- and neuroprotective. The safety and effect of a single dose of exenatide, a short-acting GLP-1RA, on cerebral and peripheral arterial function remain unknown.MethodsIn this randomized, double-blind pilot trial, we assigned elderly healthy volunteers without diabetes and no previous history of stroke to receive a single dose of subcutaneous exenatide (5 μg) or placebo. Primary outcome was immediate changes over time in blood flow velocity of the middle cerebral arteries (VMCA) assessed by repeated transcranial Doppler measurements. Secondary outcomes were changes in peripheral arterial function with finger plethysmography, ankle-brachial index (ABI), and inflammatory- and endothelial-specific biomarkers.ResultsHealthy volunteers (13 women and 17 men) were included: (mean ± standard deviation) age: 62 ± 8 years; body weight: 79.6 ± 12.7 kg; VMCA: 65.3 ± 10.7 cm/s; fasting plasma glucose: 5.5 ± 0.5 mmol/L; HbA1c: 33.9 ± 4.1 mmol/mol (5.3 ± 0.38%). No differences between exenatide and placebo group were seen regarding VMCA (p = 0.058), systolic ABI (p = 0.71), plethysmography (p = 0.45), tumor necrosis factor (p = 0.33), interleukin-6 (p = 0.11), interleukin-1β (p = 0.34), vascular cell adhesion molecule 1 (p = 0.73), intercellular adhesion molecule 1 (p = 0.74), or E-selectin (p = 0.31). No severe adverse events were observed.ConclusionA single dose of exenatide did not change cerebral blood flow velocity or peripheral vessel function in elderly healthy volunteers. The medication was safe to use in persons without diabetes allowing us to investigate this drug further in search of the neuroprotective mechanisms.Clinical Trial Registrationhttps://clinicaltrials.gov, Identifier NCT02838589.

Government Regulation Regarding Act or abbreviated as Perppu is a Legislation stipulated by the President in the case of crucial urges. The substance of Government Regulation Regarding Act is the same as the substance of the Act. It is based on the Constitution of the Republic of Indonesia Year 1945 Jo. Law No. 12 Year 2011 on the Establishment of Legislation. It studied in this paper that the position of regulation has in the Constitution of the Republic of Indonesia Year 1945 after the amendment and regulation has in the perspective of the concept of legal state. In interpreting the term "happenings crunch that forced" in the issuance of regulation has, then it should act in more detail translate the will of Section 22A of the Constitution of the Republic of Indonesia Year 1945. This research is descriptive and normative approach. The nature of "happenings crunch that forced" in the context of the state is only seen as an aspect of the prerogative of the President without judging cheks and balances system testing mechanism Perppu by Parliament.

Abstract Background Breast cancer is a heterogeneous disease at the clinical and molecular level. In this study we integrate classifications extracted from five different molecular levels in order to identify integrated subtypes. Methods Tumor tissue from 425 patients with primary breast cancer from the Oslo2 study was cut and blended, and divided into fractions for DNA, RNA and protein isolation and metabolomics, allowing the acquisition of representative and comparable molecular data. Patients were stratified into groups based on their tumor characteristics from five different molecular levels, using various clustering methods. Finally, all previously identified and newly determined subgroups were combined in a multilevel classification using a “cluster-of-clusters” approach with consensus clustering. Results Based on DNA copy number data, tumors were categorized into three groups according to the complex arm aberration index. mRNA expression profiles divided tumors into five molecular subgroups according to PAM50 subtyping, and clustering based on microRNA expression revealed four subgroups. Reverse-phase protein array data divided tumors into five subgroups. Hierarchical clustering of tumor metabolic profiles revealed three clusters. Combining DNA copy number and mRNA expression classified tumors into seven clusters based on pathway activity levels, and tumors were classified into ten subtypes using integrative clustering. The final consensus clustering that incorporated all aforementioned subtypes revealed six major groups. Five corresponded well with the mRNA subtypes, while a sixth group resulted from a split of the luminal A subtype; these tumors belonged to distinct microRNA clusters. Gain-of-function studies using MCF-7 cells showed that microRNAs differentially expressed between the luminal A clusters were important for cancer cell survival. These microRNAs were used to validate the split in luminal A tumors in four independent breast cancer cohorts. In two cohorts the microRNAs divided tumors into subgroups with significantly different outcomes, and in another a trend was observed. Conclusions The six integrated subtypes identified confirm the heterogeneity of breast cancer and show that finer subdivisions of subtypes are evident. Increasing knowledge of the heterogeneity of the luminal A subtype may add pivotal information to guide therapeutic choices, evidently bringing us closer to improved treatment for this largest subgroup of breast cancer.

The multi-party system is a system that consists of more than two dominant parties. Under the provisions of Article 6 and Article 6A the Constitution NRI 1945 Results Changes in the election of the President and Vice President of the Republic of Indonesia using the direct election system based on the proposals of the political party or coalition of political parties. If if adopted multi-party system, the presidential election will take place on the basis of a compromise between several parties contained therein. This was done because among the party that produced no outright majority. President elected in this way, would not want or desire should always pay attention to political parties that support it. The formulation of the problem is How the Implementation of the System Setup Multi Party in Indonesia? How to Influence System Against Multi Party Presidential Position In the presidential system of government in Indonesia? The research method is a normative juridical approach. Normative juridical approach method used to assess or analyze secondary data in the form of legal materials, especially primary law materials and secondary legal materials. Indonesia adheres to to multi-party presidential system. Multi-party system has been running since 1945 and runs until today even though some time has been changed the system of government. Post-reform, democratic system in Indonesia entered a new era, especially in an election in Indonesia. In a presidential system of government, multi-party system affect the difficulty of candidates for President and vice president produce a majority in the election.

Previously we have shown that our Healthy Eating Decisions school-based intervention can influence students’ selections of the healthiest foods available in their elementary school cafeterias through positive reinforcement techniques. Although effective, we recognized that students were missing fundamental nutrition knowledge necessary to understand why the Healthy Eating Decisions program identified particular beverages and foods as the healthiest in the cafeteria. Therefore, we developed the Boss’ Healthy Buddies nutrition education resource as a freely available curriculum matched with South Carolina education standards and designed for elementary school students from kindergarten through fourth grade. The current study implemented Boss’ Healthy Buddies and compared its efficacy to a commercially available nutrition program, CATCH. Elementary school students in Spartanburg, South Carolina, received weekly twenty-minute Boss’ Healthy Buddies lessons for eight weeks. Results from preassessment and postassessment surveys were compared with a positive control elementary school using the CATCH program and a negative control school receiving no nutrition education. Results show that Boss’ Healthy Buddies was equally effective as the CATCH program in improving the nutrition attitudes regarding healthiest beverages and food selections with the advantage of being freely available and minimizing the impact on classroom instruction time. In order to reduce most effectively the high prevalence of childhood overweight and obesity, it is crucial that children are taught nutrition education to support healthy eating habits at an early age. Both the Healthy Eating Decisions school-based intervention and the Boss’ Healthy Buddies nutrition education program are available online for use as free resources to aid in reducing childhood overweight and obesity within elementary schools.

The E-cadherin-catenin complex provides cell-cell adhesion. In order for a carcinoma to metastasize, cancer cells must let go of their hold of neighboring cells in the primary tumor. The presence of components of the E-cadherin-catenin complex in 246 rectal adenocarcinomas was examined by immunohistochemistry and compared to their presence in 219 colon carcinomas. The expression data were correlated to clinical information from the patients' records. There were statistically significant differences in protein expression between the rectal and the colon carcinomas regarding membranous 𝛽-catenin, 𝛾-catenin, p120-catenin, and E-cadherin, as well as nuclear 𝛽-catenin. In the rectal carcinomas, there was a significant inverse association between the expression of p120-catenin in cell membranes of the primary tumors and the occurrence of local recurrence, while membranous protein expression of 𝛽-catenin was inversely related to distant metastases.

Adenocarcinomas of rectum and colon may be different with regard to the cellular biological basis for cancer development. A material of 246 rectal cancers removed surgically at Akershus University Hospital in the years 1992–2000 was investigated and was compared to a material of 219 colon cancers operated on at Akershus University Hospital during the years 1988, 1990 and 1997–2000. There were highly significant differences between the rectal and the colon cancers in the protein expression of cyclin D1, cyclin D3, cyclin E, nuclear β-catenin, and c-Myc and in gene amplification of cyclin A2, cyclin B1, cyclin D1, and cyclin E. Gene amplification and protein expression in the rectal cancers correlated significantly for the cyclins B1, D3, and E. A statistically significant relation was observed between overexpression of cyclin A2 and local relapse of rectal carcinomas, as higher expression of cyclin A2 was associated with lower local recurrence rate.

Adult education centres provide a final opportunity for adult learners who have transitioned out of mainstream schools to earn a high school degree. These centers overwhelmingly serve low-income, African-American and Latinx students whose needs were not met by traditional schools. Adult Education Centers are underfunded, under-resourced and challenged with high attrition rates. Little is known about factors that promote adult education persistence in the adult education context. To address this, the authors conducted a cross-sectional study examining the relationship between social support, coping through emotional processing and expression, stigma consciousness and attitudes towards participation in adult education. Results indicate that higher levels of self-reported coping (via emotional processing) and social support improve attitudes towards adult education and higher levels of self-reported stigma consciousness increase negative attitudes towards adult education. Study findings have significant policy implications for constructing student centred supports for adult education students who experience multiple levels of social inequality.

The substituted tetrahydrofuran core is a structural motif in many biologically active and natural compounds. However, the scarcity of enantioselective methods developed towards its synthesis makes this field challenging and attractive to explore. Herein, the first Brønsted‐base catalyzed enantioselective (3+2) annulation of donor‐acceptor cyclopropanes with aldehydes and ketones affording enantioenriched 2,3,5‐substituted tetrahydrofurans is reported. The reaction concept is based on activation of racemic β‐cyclopropyl ketones by a chiral bifunctional Brønsted base which catalyzes the (3+2) annulation for a range of aldehydes and ketones. For aldehydes, the annulation furnished tetrahydrofurans in excellent yield, good diastereoselectivity and with excellent enantioselectivity up to >99 % ee. Surprisingly, aromatic aldehydes afforded the cis‐2,5‐substituted tetrahydrofurans as the major diastereoisomer, while for aliphatic aldehydes the trans‐cycloadduct was favored. The reaction also proceeds well for ketones affording spiro tetrahydrofurans in excellent yields and enantioselectivities (up to 99 % ee). Hammett studies have been conducted to elucidate the influence of the electronic nature of benzaldehydes on the stereoselectivity. Based on the diastereochemical outcome for the aldehydes, two reaction paths for aromatic and aliphatic aldehydes are proposed. Finally, two diastereoselective synthetic transformations have been conducted to demonstrate the synthetic potential of the obtained products. [ABSTRACT FROM AUTHOR]

Genome-wide association studies have identified numerous loci linked to breast cancer susceptibility, but the mechanism by which variations at these loci influence susceptibility is usually unknown. Some variants are only associated with particular clinical subtypes of breast cancer. Understanding how and why these variants influence subtype-specific cancer risk contributes to our understanding of cancer etiology. We conducted a genome-wide expression Quantitative Trait Locus (eQTL) study in a discovery set of 287 breast tumors and 97 normal mammary tissue samples and a replication set of 235 breast tumors. We found that the risk-associated allele of rs7716600 in the 5p12 estrogen receptor-positive (ER-positive) susceptibility locus was associated with elevated expression of the nearby gene MRPS30 exclusively in ER-positive tumors. We replicated this finding in 235 independent tumors. Further, we showed the rs7716600 risk genotype was associated with decreased MRPS30 promoter methylation exclusively in ER-positive breast tumors. In vitro studies in MCF-7 cells carrying the protective genotype showed that estrogen stimulation decreased MRPS30 promoter chromatin availability and mRNA levels. In contrast, in 600MPE cells carrying the risk genotype, estrogen increased MRPS30 expression and did not affect promoter availability. Our data suggest the 5p12 risk allele affects MRPS30 expression in estrogen-responsive tumor cells after tumor initiation by a mechanism affecting chromatin availability. These studies emphasize that the genetic architecture of breast cancer is context-specific, and integrated analysis of gene expression and chromatin remodeling in normal and tumor tissues will be required to explain the mechanisms of risk alleles.

Rice is the food source for the community, including in the South Sulawesi area. Consequently, proper management is needed to support optimal production results. Several farmers are currently starting to develop organic farming systems due to the shortcomings of the conventional farming system such as the use of chemical inputs, land degradation, and decreased production. This study aims to compare the organic farming developed by farmers with conventional farming systems in terms of land ownership, input, soil quality, and productivity. This research used a simple random sampling method to collect land and production data from 130 farmers (90 conventional, 40 organic).In general, in South Sulawesi, the organic farming system is better than conventional farming systems. The inputs in the conventional are certified seeds, chemical fertilizers, and pesticides, which will affect costs and have an effect in the long term. Meanwhile, in an organic farming system, seed needs are met independently by farmers, using organic materials (manure, compost, bokashi) and biopesticides. Productivity also shows that the organic farming system increases production than conventional farming. In the future, farmers can start to develop an organic farming system by adding various organic ingredients to support their field performance.

To compare the cumulative impact of sequential wear on mechanical properties and appearance of a composite resin (CR), Filtek Z250®, a glass ionomer GI, Fuji IX GP®, and a glass hybrid (GH), Equia Forte®. Six equally sized specimens of each material were subjected to wear tests, i.e., simulation of brushing, chewing and acidic liquid exposure, mimicking at least 6 months of clinical exposure. Surface roughness, hardness, substance loss and degree of shade lightness were determined. Following wear tests, significant increase in surface roughness and decrease in hardness values were observed for all materials (p <.05). Significantly larger substance loss was found in Equia Forte® specimens compared to Filtek Z250® (p <.05), while that of Fuji IX® exceeded the measurement capacity of the instrument. Opposite to the two other materials, the shade of Filtek Z250® became darker. Sequential wear exposure mimicking abrasion, erosion and attrition to products representing CR, GI and GH, caused weakening and change in appearance of the materials. The composite resin was the most mechanically resistant to the sequential wear. [ABSTRACT FROM AUTHOR]

Background We aimed to estimate XBB.1.5 vaccine effectiveness (VE) against COVID-19-related hospitalizations and deaths during BA.2.86/JN.1 predominance, among EU/EEA individuals with ≥65-years.Research design and methods We linked electronic health records to create historical cohorts in Belgium, Denmark, Italy, Navarre (Spain), Norway, Portugal and Sweden. We included individuals aged ≥65-years eligible for the autumnal 2023 COVID-19 vaccine. Follow-up started when ≥80% of country-specific sequenced viruses were BA.2.86/JN.1 (4/dec/23 to 08/jan/24) and ended 25 February 2024. At study site level, we estimated the vaccine confounder-adjusted hazard ratio (aHR) of COVID-19 hospitalizations and deaths between individuals with ≥14 days after vaccination versus unvaccinated in autumn 2023, overall, by time since vaccination and age groups. VE was estimated as (1-pooled aHR)x100 with a random-effects model.Results XBB.1.5 VE against COVID-19 hospitalizations was 50% (95%CI: 45 to 55) and 41% (95%CI: 35 to 46) in 65–79-year-olds and in ≥80-year-olds, respectively. VE against COVID19-related-death was 58% (95%CI: 42 to 69) and 48% (95%CI: 38 to 57), respectively, in both age groups. VE estimates against each outcome declined in all age groups over time.Conclusion Monovalent XBB.1.5 vaccine had a moderate protective effect against severe and fatal COVID-19 likely caused by BA.2.86/JN.1 during the 2023/2024 winter, among persons aged ≥65.

Abstract Circulating tumor DNA (ctDNA) has shown potential as a non-invasive tumor biomarker in neuroblastoma. Previous studies used generic assays for detection of selected predefined oncogenic variants as markers of ctDNA, which limits the sensitivity and excludes a subset of patients from analysis. Here we assessed patient-specific ctDNA analysis for treatment evaluation and detection of relapse in neuroblastoma. We generated personalized sequencing panels targeting 10 tumor-specific single nucleotide variants (SNVs) for each patient and performed ctDNA analysis of 136 plasma samples collected longitudinally in 13 children with neuroblastoma. ctDNA was detected using ultra-deep next generation sequencing with unique molecular identifiers to eliminate polymerase-induced errors. We found that the levels of ctDNA at diagnosis correlated with risk group and decreased gradually during effective treatment. All samples collected during follow-up in patients without disease relapse were ctDNA-negative. All four relapses were associated with elevated ctDNA levels, and a majority of the analyzed SNVs were detected at time of relapse. In one case, ctDNA became positive 78 days before the relapse was diagnosed with routine assessment and increased by over a thousandfold before the start of additional treatment. Overall, ctDNA was more uniformly elevated at diagnosis, showed less putative false positive results, and was more sensitive for detection of relapse compared to five serum or urine tumor markers used in clinical routine. In conclusion, personalized ctDNA analysis is suitable for clinical monitoring of tumor burden and may be used in all neuroblastoma patients regardless of risk group or tumor genetics.

This community service activity aims to increase the community's knowledge and skills in using chopping machines, which is a basic skill in managing litter and agricultural waste into compost and processing livestock forage into silage. Service activities were carried out in Tempurejo village, Kediri Regency with a total of 36 partners. The method used in this service is an empowerment based on collaborative participation. The activity stages follow the community empowerment implementation model, namely ODSIMED (Observation, Development, Socialisation, Implementation, Monitoring, Evaluation and Desemination). The instrument used to measure community knowledge and skills is a questionnaire and the data is analyzed quantitatively. The results of this service show that partners (1) are able to determine chopped materials for making compost or silage, achieving an average skill score of 3.27, (2) are able to differentiate the function of each part of the machine, achieving an average skill score of 3.30, (3) able to turn on and turn off the machine with a partner skill score reaching 3.20, (4) able to produce various forms of shreds both for compost and silage making purposes achieving an average score of 3.50, (5) able to calculate production capacity reaching the average skill score is 3.40, and (6) being able to carry out maintenance on machines reaches an average skill score of 2.80.

Introduction: Environmental temperature conditions might influence the composition of secondary metabolites in certain medicinal plants. This study aimed to examine how some of the phytochemicals and anticancer properties of Carpobrotus edulis may be impacted by temperature conditions. Methods: The plant specimens were kept in growth chambers at 15/10 °C and 45/35 °C (day/night), and harvested at 48-hour intervals (48, 96, and 144 hours). Control conditions were maintained at 25/15 °C. Standard phytochemical colour tests were used to determine the presence of eight phytochemicals. The anticancer activity against cervical cancer cell lines was determined using cell viability assay, cell morphology, Hoechst staining, and wound healing assays. Results: The phytochemical screening showed the presence of all tested phytochemicals (phenolics, flavonoids, terpenoids, saponins, tannins, steroids, and cardiac glycosides) in all treatments except for saponins in the 96- and 144-hour temperature treatments. A noteworthy IC50 value of 284.9 µg/mL was determined from the methanolic leaf extract exposed to high temperatures for 144 hours against cervical cancer. Treatment with this extract suggested changes in cancer cell morphology, signs of apoptosis, and cell migration inhibition. Conclusion: The preliminary results obtained suggest that the C. edulis methanolic extract has potential anticancer properties against cervical cancer. These observations may have implications for the indigenous plant use in treating various ailments and broaden the type of anticancer research involving this plant.

Abstract Background Rhabdomyosarcoma (RMS) is the most common pediatric soft tissue sarcoma, with embryonal (ERMS) and alveolar (ARMS) representing the two most common histological subtypes. ARMS shows poor prognosis, being often metastatic at diagnosis. Thus, the discovery of novel biomarkers predictive of tumor aggressiveness represents one of the most important challenges to overcome and may help the development of tailored therapies. In the last years, miRNAs carried in extracellular vesicles (EVs), small vesicles of endocytic origin, have emerged as ideal candidate biomarkers due to their stability in plasma and their tissue specificity. Methods EVs miRNAs were isolated from plasma of 21 patients affected by RMS and 13 healthy childrens (HC). We performed a miRNA profile using the Serum/Plasma Focus microRNA PCR panels (Qiagen), and RT-qPCR for validation analysis. Statistically significant (p

Abstract Development of new vaccines tailored for difficult-to-target diseases is hampered by a lack of diverse adjuvants for human use, and none of the currently available adjuvants induce Th17 cells. Here, we develop a liposomal adjuvant, CAF®10b, that incorporates Mincle and Toll-like receptor 9 agonists. In parallel mouse and non-human primate studies comparing to CAF® adjuvants already in clinical trials, we report species-specific effects of adjuvant composition on the quality and magnitude of the responses. When combined with antigen, CAF®10b induces Th1 and Th17 responses and protection against a pulmonary infection with Mycobacterium tuberculosis in mice. In non-human primates, CAF®10b induces higher Th1 responses and robust Th17 responses detectable after six months, and systemic and pulmonary Th1 and Th17 recall responses, in a sterile model of local recall. Overall, CAF®10b drives robust memory antibody, Th1 and Th17 vaccine-responses via a non-mucosal immunization route across both rodent and primate species.