Upaya Meningkatkan Keterampilan Membaca Aksara Jawa melalui Media Audio Visual pada Siswa Kelas IV SD Negeri 2 Gadingharjo Sanden Bantul

This study aimed to describe (1) students\u27 activities in the teaching of reading skills of Java letters through audio visual media and (2) the improvement of reading skills of Java letters through audio visual media among the fourth grade students of SD Negeri 2 Gadingharjo. The type of this study was classroom action research in the teaching of reading skills of Java letters. The subject of the research was the fourth grade students of SD Negeri 2 Gdaingharjo Sanden Bantul consisted of 39 students. The object of the research was reading skills of Java letters. Data collecting methods used test, observation, and documentation. This research used validity by using expert judgment. This study shows that (1) the use of audio visual could improve the students\u27 activities among the fourth grade students of SD Negeri 2 Gadingharjo. The students\u27 activities in pre cycle was 38.97%, cycle I was 67.69%, and cycle II was 89.74%. (2) The use of audio visual media could improve reading skill of Java letters among the fourth grade students of SD Negeri 2 Gadingharjo. The students\u27 reading skills show that there was an improvement from pre cycle until cycle II. The percentage of complete learning from pre cycle was 35.90% became 61.54% in cycle I and more improved in cycle II became 87.18%. It could be concluded that the use of audio visual media could improve learning activities and reading skills of Java letters

SOST Inhibits Prostate Cancer Invasion.

Inhibitors of Wnt signaling have been shown to be involved in prostate cancer (PC) metastasis; however the role of Sclerostin (Sost) has not yet been explored. Here we show that elevated Wnt signaling derived from Sost deficient osteoblasts promotes PC invasion, while rhSOST has an inhibitory effect. In contrast, rhDKK1 promotes PC elongation and filopodia formation, morphological changes characteristic of an invasive phenotype. Furthermore, rhDKK1 was found to activate canonical Wnt signaling in PC3 cells, suggesting that SOST and DKK1 have opposing roles on Wnt signaling in this context. Gene expression analysis of PC3 cells co-cultured with OBs exhibiting varying amounts of Wnt signaling identified CRIM1 as one of the transcripts upregulated under highly invasive conditions. We found CRIM1 overexpression to also promote cell-invasion. These findings suggest that bone-derived Wnt signaling may enhance PC tropism by promoting CRIM1 expression and facilitating cancer cell invasion and adhesion to bone. We concluded that SOST and DKK1 have opposing effects on PC3 cell invasion and that bone-derived Wnt signaling positively contributes to the invasive phenotypes of PC3 cells by activating CRIM1 expression and facilitating PC-OB physical interaction. As such, we investigated the effects of high concentrations of SOST in vivo. We found that PC3-cells overexpressing SOST injected via the tail vein in NSG mice did not readily metastasize, and those injected intrafemorally had significantly reduced osteolysis, suggesting that targeting the molecular bone environment may influence bone metastatic prognosis in clinical settings

Emergence of Epizootic Ulcerative Syndrome in Native Fish of the Murray-Darling River System, Australia: Hosts, Distribution and Possible Vectors

Epizootic ulcerative syndrome (EUS) is a fish disease of international significance and reportable to the Office International des Epizootics. In June 2010, bony herring Nematalosa erebi, golden perch Macquaria ambigua, Murray cod Maccullochella peelii and spangled perch Leiopotherapon unicolor with severe ulcers were sampled from the Murray-Darling River System (MDRS) between Bourke and Brewarrina, New South Wales Australia. Histopathology and polymerase chain reaction identified the fungus-like oomycete Aphanomyces invadans, the causative agent of EUS. Apart from one previous record in N. erebi, EUS has been recorded in the wild only from coastal drainages in Australia. This study is the first published account of A. invadans in the wild fish populations of the MDRS, and is the first confirmed record of EUS in M. ambigua, M. peelii and L. unicolor. Ulcerated carp Cyprinus carpio collected at the time of the same epizootic were not found to be infected by EUS, supporting previous accounts of resistance against the disease by this species. The lack of previous clinical evidence, the large number of new hosts (n = 3), the geographic extent (200 km) of this epizootic, the severity of ulceration and apparent high pathogenicity suggest a relatively recent invasion by A. invadans. The epizootic and associated environmental factors are documented and discussed within the context of possible vectors for its entry into the MDRS and recommendations regarding continued surveillance, research and biosecurity are made

Identification of a bone morphogenetic protein type 2 receptor neutralizing antibody

The bone morphogenetic protein (BMP) signaling pathway comprises the largest subdivision of the transforming growth factor (TGFβ) superfamily. BMP signaling plays essential roles in both embryonic development and postnatal tissue homeostasis. Dysregulated BMP signaling underlies human pathologies ranging from pulmonary arterial hypertension to heterotopic ossification. Thus, understanding the basic mechanisms and regulation of BMP signaling may yield translational opportunities. Unfortunately, limited tools are available to evaluate this pathway, and genetic approaches are frequently confounded by developmental requirements or ability of pathway components to compensate for one another. Specific inhibitors for type 2 receptors are poorly represented. Thus, we sought to identify and validate an antibody that neutralizes the ligand-binding function of BMP receptor type 2 (BMPR2) extracellular domain (ECD)

Homozygous NLRP1 gain-of-function mutation in siblings with a syndromic form of recurrent respiratory papillomatosis

© 2019 National Academy of Sciences. All rights reserved. Juvenile-onset recurrent respiratory papillomatosis (JRRP) is a rare and debilitating childhood disease that presents with recurrent growth of papillomas in the upper airway. Two common human papillomaviruses (HPVs), HPV-6 and -11, are implicated in most cases, but it is still not understood why only a small proportion of children develop JRRP following exposure to these common viruses. We report 2 siblings with a syndromic form of JRRP associated with mild dermatologic abnormalities. Whole-exome sequencing of the patients revealed a private homozygous mutation in NLRP1, encoding Nucleotide-Binding Domain Leucine-Rich Repeat Family Pyrin Domain-Containing 1. We find the NLRP1 mutant allele to be gain of function (GOF) for inflammasome activation, as demonstrated by the induction of inflammasome complex oligomerization and IL-1β secretion in an overexpression system. Moreover, patient-derived keratinocytes secrete elevated levels of IL-1β at baseline. Finally, both patients displayed elevated levels of inflammasome-induced cytokines in the serum. Six NLRP1 GOF mutations have previously been described to underlie 3 allelic Mendelian diseases with differing phenotypes and modes of inheritance. Our results demonstrate that an autosomal recessive, syndromic form of JRRP can be associated with an NLRP1 GOF mutation

Impact of age on NIS2+™ and other non-invasive blood tests for the evaluation of liver disease and detection of at-risk MASH

\ua9 2024 The Author(s)Background & Aims: Robust performance of non-invasive tests (NITs) across ages is critical to assess liver disease among patients with metabolic dysfunction-associated liver disease (MASLD). We evaluated the impact of age on the performance of NIS2+™ vs. other NITs. Methods: An analysis cohort (N = 1,926) with biopsy-proven MASLD was selected among individuals screened for the phase III RESOLVE-IT clinical trial and divided into ≤45, 46–55, 56–64, and ≥65 years groups. To avoid potential confounding effects, a well-balanced cohort (n = 708; n = 177/age group) was obtained by applying a propensity score-matching algorithm to the analysis cohort. Baseline values of biomarkers and NITs were compared across age groups using one-way ANOVA, and the impact of age and histology were compared through three-way ANOVA. The impact of age on NIT performance for the detection of at-risk metabolic dysfunction-associated steatohepatitis (MASH; MASLD activity score [MAS] ≥4 and fibrosis stage [F] ≥2) was also evaluated. Results: Age did not affect the distributions of NIS2+™ and APRI (aspartate aminotransferase-to-platelet ratio index), but significantly (p <0.0001) impacted those of NFS (NAFLD fibrosis score), FIB-4 (Fibrosis-4 index), and Enhanced Liver Fibrosis (ELF™) score. NIS2+™ was the only NIT on which fibrosis and MAS exerted a moderate to large effect. While the impact of fibrosis on APRI was moderate, that of MAS was low. The impact of age on FIB-4 and NFS was larger than that of fibrosis. NIS2+™ exhibited the highest AUROC values for detecting at-risk MASH across age groups, with stable performances irrespective of cut-offs. Conclusions: NIS2+™ was not significantly impacted by age and was sensitive to both fibrosis and MAS grade, demonstrating a robust performance to rule in/out at-risk MASH with fixed cut-offs. Impact and Implications: While metabolic dysfunction-associated steatotic liver disease (MASLD) can affect individuals of all ages, patient age could represent an important confounding factor when interpreting non-invasive test (NIT) results, highlighting the need for reliable and efficient NITs that are not impacted by age and that could be interpreted with fixed cut-offs, irrespective of patient age. We report the impact of age on different well-established NITs – among those tested, only two panels, NIS2+™ and APRI, were not impacted by age and can be used and interpreted independently of patient age. NIS2+™ was also sensitive to both fibrosis and MAS, further confirming its efficiency for the detection of the composite endpoint of at-risk MASH and its potential as a valuable candidate for large-scale implementation in clinical practice and clinical trials

A Smartphone App to Reduce Sugar-Sweetened Beverage Consumption Among Young Adults in Australian Remote Indigenous Communities: Design, Formative Evaluation and User-Testing

©Emma Tonkin, Lauren Jeffs, Thomas Philip Wycherley, Carol Maher, Ross Smith, Jonathon Hart, Beau Cubillo, Julie Brimblecombe. Originally published in JMIR Mhealth and Uhealth (http://mhealth.jmir.org), 12.12.2017. This is an open-access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work, first published in JMIR mhealth and uhealth, is properly cited. The complete bibliographic information, a link to the original publication on http://mhealth.jmir.org/, as well as this copyright and license information must be included.Background: The disproportionate burden of noncommunicable disease among Indigenous Australians living in remote Indigenous communities (RICs) is a complex and persistent problem. Smartphones are increasingly being used by young Indigenous adults and therefore represent a promising method to engage them in programs seeking to improve nutritional intake. Objective: This study aimed to consult RIC members to inform the content of a smartphone app that can be used to monitor and reduce sugar-sweetened beverage intake in RICs. Methods: The study was conducted in two phases. The formative phase involved a simulated grocery selection activity with think aloud (“think aloud shop”), a semistructured interview, a questionnaire outlining current smartphone and app use, and a paper prototyping activity. A preliminary end-user testing phase involved a think aloud prototype test and a semistructured interview regarding user satisfaction. Convenience sampling was used to recruit 20 18- to 35-year-old smartphone users for each phase from two RICs in the Northern Territory, Australia. Thematic analysis of transcribed audio recordings was used to identify determinants of food choice from the think aloud shop; themes related to the Theory of Planned Behavior (TPB) from the eating behaviors interview; and usability, comprehension, and satisfaction with the app from the preliminary end-user testing. Results: Smartphone use in RICs is currently different to that found in urban environments; in particular, extremely low use of Facebook, restricted variety of phone types, and limited Internet access. Findings regarding promoting app engagement indicate that utilizing an opt-in approach to social features such as leader boards and team challenges is essential. The inclusion of games was also shown to be important for satisfaction, as were the use of audio features, contextually embedded dissemination, and streamlined app design for comprehension in this target group. Conclusions: This research provides critical insights and concrete recommendations for the development of lifestyle improvement apps targeted toward disadvantaged young adults in nonurban settings, specifically RICs. It serves as a framework for future app development projects using a consultative user-centered design approach, supporting calls for the increased use of this strategy in app development