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Down-staging is commonly used to select patients with hepatocellular carcinoma (HCC) beyond Milan criteria (MC) for liver transplantation (LT), but outcomes are heterogenous. We aimed to estimate pooled down-staging success rates, HCC recurrence, and overall survival (OS), stratified by criteria used for baseline tumor burden.We searched Pubmed and EMBASE databases from inception until August 2021 for studies reporting down-staging success (reduction of tumor burden to within MC) and outcomes of adult HCC patients. In addition, we performed a pooled analysis using reconstructed individual participant data to obtain robust estimates for OS.We screened 1059 articles and included 25 articles involving 3997 patients. Overall, 55.16% (45.49%-64.46%) underwent successful down-staging, and 31.52% (24.03%-40.11%) received LT (by intention-to-treat analysis [ITT]). Among patients who received LT, 16.01% (11.80%-21.37%) developed HCC recurrence. Comparing studies that used the United Network for Organ Sharing Down-Staging (UNOS-DS) criteria versus studies beyond UNOS-DS or did not specify criteria, down-staging success (by ITT) was 83.21% versus 45.93%, P.001; the proportion who received LT (by ITT) was 48.61% vs 28.60%, P = .030; and HCC recurrence (among patients who received LT) occurred in 9.06% versus 20.42%, P.001. Among studies that used UNOS-DS criteria, ITT 1- and 5-year OS from the initiation of down-staging treatment was 86% and 58%, respectively, whereas 1- and 5-year post-LT OS was 94% and 74%, respectively.Among studies that adhered to UNOS-DS criteria, down-staging was successful in four-fifths of patients,50% received LT, and post-LT outcomes were excellent. These data provide clinical validation for the utilization of UNOS-DS criteria.

Background: Influenza vaccines have been demonstrated to effectively reduce the incidence of influenza infection and potentially associated risks of cardiovascular events in patients with cardiovascular disease (CVD). Despite strong guideline and public health endorsements, global influenza vaccination rates in patients with CVD are highly variable. This prespecified analysis of NUDGE-FLU (Nationwide Utilization of Danish Government Electronic Letter System for Increasing Influenza Vaccine Uptake) examined the effect of digital behavioral nudges on influenza vaccine uptake based on the presence of CVD. Methods: NUDGE-FLU was a randomized, pragmatic, nationwide, register-based trial that included Danish citizens 65 years of age or older during the 2022 to 2023 influenza season. Households were randomized in a 9:1:1:1:1:1:1:1:1:1 ratio to usual care or 9 electronic letters with designs based on behavioral concepts. Danish nationwide registers were used to collect baseline and outcome data. The primary end point was receipt of an influenza vaccine on or before January 1, 2023. The effects of the intervention letters were examined according to the presence of CVD and across cardiovascular subgroups that included heart failure, ischemic heart disease, and atrial fibrillation. Results: Of 964 870 NUDGE-FLU participants from 691 820 households, 264 392 (27.4%) had CVD. During follow-up, 83.1% of participants with CVD versus 79.2% of participants without CVD received an influenza vaccination ( P P for interaction=0.41). A repeated letter strategy with a reminder follow-up letter 14 days later was also effective in increasing influenza vaccination, irrespective of CVD (CVD: absolute difference, +0.80 percentage points [99.55% CI, –0.27 to 1.86]; no CVD: +0.67 percentage points [99.55% CI, –0.06 to 1.40]; P for interaction=0.77). Effectiveness of both nudging strategies was consistent across all major CVD subgroups. None of the other 7 nudging strategies were effective, regardless of CVD status. Conclusions: Electronic letter interventions emphasizing the potential cardiovascular benefits of influenza vaccination and using a reminder letter strategy were similarly beneficial in increasing influenza vaccination rates among older adults with and without CVD and across cardiovascular subgroups. Electronic nudges may improve influenza vaccine uptake in individuals with CVD. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT05542004.

This study aims to describe how the economic impact of the poor has on the quality of education, the implementation of the financing system in the system of dhuafa schools, as well as the supporting and inhibiting factors. The object of research is the MEKARSARI 01 Middle School. The sampling technique uses purposive sampling with the subject of the principal, teacher and parents of students. Data analysis techniques using Interactive Model Analysis. Methods of data collection using observation and interviews. Checking the validity of the data using data and source triangulation techniques. The results of the research indicate that elements of the government (especially the scope of education) and the organizations concerned provide assistance in the form of surplus funds so that the smooth running of the educational process can be maintained. The researcher hopes that further research will try to make or formulate an efficient practicum model for the poor.

The obesity epidemic is a global health concern with Asian countries facing one of the most rapid rises in obesity rates. However, given the underwhelming long-term efficacy of weight loss strategies, especially in Asia, this review aims to explore barriers and facilitators to weight management of patients with overweight and obesity in Asia.Medline, CINAHL, PsycINFO and Web of Science were searched for articles discussing barriers and facilitators of treatment to obesity from both healthcare professionals (HCPs) and patients. Qualitative and mixed method studies from Asia were included. Key quotes were extracted, coded, and thematically analysed with reference to Thomas and Harden's methodology.A total of 26 articles were included in this review. From the patients' perspective, three main themes were identified, factors influencing poor eating behaviour, inhibiting lifestyle modifications, and facilitating lifestyle modifications. Patients highlighted several barriers including the lack of social support, physiological limitations to exercise and low health literacy. Rigid sociocultural norms and lack of accessible healthcare services, exercise facilities and healthy food exacerbated the barriers. Facilitators to lifestyle modifications consisted of strong support systems and high health literacy. HCPs agreed that low health literacy, lack of social support and patient motivation impeded patients' weight loss attempts but were unaware of the other barriers they faced.There are discrepancies between ideas of barriers and facilitators of HCPs and patients. A mixture of population-level, primary care, and personal interventions are required to address this disparity and enhanced health literacy would improve weight loss outcomes.

OBJECTIVE Lumbar interbody cage subsidence has a multifactorial etiology. Cage material, although well studied after transforaminal lumbar interbody fusion, has not been investigated as a contributing factor to subsidence after lateral lumbar interbody fusion (LLIF). In this study the authors compared rates of subsidence and reoperation after LLIF between polyetheretherketone (PEEK) and 3D-printed porous titanium (pTi) in an institutional propensity score–matched and cost analysis. METHODS This is a retrospective observational cohort analysis of adult patients who underwent LLIF with pTi versus PEEK between 2016 and 2020. Demographic, clinical, and radiographic characteristics were collected. Propensity scores were calculated and 1:1 matching without replacement of surgically treated levels was performed. The primary outcome of interest was subsidence. The Marchi subsidence grade was determined at the time of last follow-up. Chi-square or Fisher’s exact tests were used to compare subsidence and reoperation rates between lumbar levels treated with PEEK versus pTi. Modeling and cost analysis were performed using TreeAge Pro Healthcare. RESULTS The authors identified a total of 192 patients; 137 underwent LLIF with PEEK (212 levels) and 55 had LLIF with pTi (97 levels). After propensity score matching, a total of 97 lumbar levels remained in each treatment group. After matching, there were no statistically significant differences between groups in baseline characteristics. Levels treated with pTi were significantly less likely to exhibit subsidence (any grade) compared to those treated with PEEK (8% vs 27%, p = 0.001). Five (5.2%) levels treated with PEEK required reoperation for subsidence, but only 1 (1.0%) level treated with pTi required reoperation for subsidence (p = 0.12). Given subsidence and revision rates experienced in the cohorts in this study, the pTi interbody device is economically superior to PEEK in a single-level LLIF as long as its cost is at least $1185.94 lower than that of PEEK. CONCLUSIONS The pTi interbody device was associated with less subsidence, but statistically similar revision rates after LLIF. pTi is potentially a superior economic choice at this study’s reported revision rate.

Increasing life expectancy and sedentary lifestyle in the elderly have an impact on physical changes, especially degenerative joint disease. Exercise is a modality that can provide physiological and therapeutic effects so that it can prevent, treat, and improve the quality of health. However, to find an exercise design that has the desired therapeutic effect requires a long journey and in-depth study. Many recent studies have shown that exercise initiates the secretion of proteins and tissue regeneration hormones which are very necessary for anti-aging in the elderly. The purpose of this study is to further enrich the exercise design which can be used as a reference for the high-risk elderly population and the elderly in general so that the quality of life and life expectancy are getting longer. The research method used pre and post design experimental studies through the purposive sampling technique method which was divided into 4 groups consisting of the control group, experimental group 1 and experimental group 2 which were carried out in August-October 2022 at Balai Warga RT 08 Kembangan Village, West Jakarta. Samples that met the inclusive and exclusion criteria were obtained by 18 respondents. To determine the range of motion and balance function assessment, the sample was measured with a range of motion and balance test instrument. Data were analyzed using a paired sample t-test to determine the effect of stabilization exercises on joint motion and balance function. Statistical test results p=0,001, (p0.05). The conclusion is that stabilization exercises affect the range of motion in degenerative joint pain.

Conventional randomized controlled trials (RCTs) can be expensive, time intensive, and complex to conduct. Trial recruitment, participation, and data collection can burden participants and research personnel. In the past two decades, there have been rapid technological advances and an exponential growth in digitized healthcare data. Embedding RCTs, including cardiovascular outcome trials, into electronic health record systems or registries may streamline screening, consent, randomization, follow-up visits, and outcome adjudication. Moreover, wearable sensors (i.e. health and fitness trackers) provide an opportunity to collect data on cardiovascular health and risk factors in unprecedented detail and scale, while growing internet connectivity supports the collection of patient-reported outcomes. There is a pressing need to develop robust mechanisms that facilitate data capture from diverse databases and guidance to standardize data definitions. Importantly, the data collection infrastructure should be reusable to support multiple cardiovascular RCTs over time. Systems, processes, and policies will need to have sufficient flexibility to allow interoperability between different sources of data acquisition. Clinical research guidelines, ethics oversight, and regulatory requirements also need to evolve. This review highlights recent progress towards the use of routinely generated data to conduct RCTs and discusses potential solutions for ongoing barriers. There is a particular focus on methods to utilize routinely generated data for trials while complying with regional data protection laws. The discussion is supported with examples of cardiovascular outcome trials that have successfully leveraged the electronic health record, web-enabled devices or administrative databases to conduct randomized trials.

This study aims to reduce heat gain and minimise cooling energy through building envelope material as a passive design intervention strategy to achieve thermal comfort. Integrated Learning Building in the Faculty of Engineering, Universitas Indonesia, is used as a case study due to its air conditioning setting. First, the material characteristic of the building envelope is calculated using the Overall Thermal Transmission Value (OTTV) calculation to determine heat gain and the EDGE (Excellence in Design for Greater Efficiencies), a software to estimate cooling energy consumption. Then, a passive design intervention strategy is performed by adding insulation (polyester, bagasse, and recycled textile and paper) and substituting window glazing (reflective, PVB laminated, and Clear IGU Low-E). The results show that the combination of recycled textile and paper insulation and clear IGU Low-E window glazing has an OTTV value of 24.89 W/m2 which is lower than the standard in Indonesia (35 W/m2). Meanwhile, the cooling energy usage shows an energy consumption of 1.14% lower, but it did not achieve the 5% reduction target. Therefore, further intervention on other parts of the building envelope, such as the roof and floor, should be observed to achieve higher energy-saving potential.

A number of different thermomechanical treatments of NiTi have been developed to overcome some of the drawbacks of the traditional NiTi alloy, namely, separation and distortion of instruments. The present study analyzes the data on nickel-titanium instruments and their cyclic fatigue resistance. Online electronic data base such as PubMed, Cochrane and Google scholar through 31 January 2000 to 31 January 2020 with only English language literature. Clinical study of 9 article review & stated that the Cyclic Fatigue Resistance Of Nickel Titanium Rotary Instruments tested in artificial blocks or canals ,tested with different NiTi rotary files between 200-500 rpm and accordingly torque under controled/uncntroled temperature in curved canls fracture occure. The findings of this systematic review and meta-analysis point to the possibility that the temperature at which the instruments are tested may affect the results of cyclic fatigue resistance on NiTi files with a different behavior depending on the heat treatment of the alloy and that an increase in the angle of curvature of artificial canals has a detrimental effect on the cyclic fatigue resistance. Reciprocal movement exhibited the best performance with regard to cyclic fatigue resistance. The thermal treatment of the instrument’s alloy, its cross section, and the glide path seem to influence the cyclic fatigue resistance. The cyclic fatigue resistance of instruments manufactured with the gold heat treatment is not influenced by room or intracanal temperature.

ImportanceGout is common in patients with heart failure (HF), and sodium-glucose cotransporter 2 inhibitors, a foundational treatment for HF, reduce uric acid levels.ObjectiveTo examine the reported prevalence of gout at baseline, the association between gout and clinical outcomes, and the effect of dapagliflozin in patients with and without gout and the introduction of new uric acid–lowering therapy and colchicine.Design, Setting, and ParticipantsThis post hoc analysis used data from 2 phase 3 randomized clinical trials conducted in 26 countries, DAPA-HF (left ventricular ejection fraction [LVEF] ≤40%) and DELIVER (LVEF >40%). Patients with New York Heart Association functional class II through IV and elevated levels of N-terminal pro–B-type natriuretic peptide were eligible. Data were analyzed between September 2022 and December 2022.InterventionAddition of once-daily 10 mg of dapagliflozin or placebo to guideline-recommended therapy.Main Outcomes and MeasuresThe primary outcome was the composite of worsening HF or cardiovascular death.ResultsAmong 11 005 patients for whom gout history was available, 1117 patients (10.1%) had a history of gout. The prevalence of gout was 10.3% (488 of 4747 patients) and 10.1% (629 of 6258 patients) in those with an LVEF up to 40% and greater than 40%, respectively. Patients with gout were more often men (897 of 1117 [80.3%]) than those without (6252 of 9888 [63.2%]). The mean (SD) age was similar between groups, 69.6 (9.8) years for patients with gout and 69.3 (10.6) years for those without. Patients with a history of gout had a higher body mass index, more comorbidity, and lower estimated glomerular filtration rate and were more often treated with a loop diuretic. The primary outcome occurred at a rate of 14.7 per 100 person-years (95% CI, 13.0-16.5) in participants with gout compared with 10.5 per 100 person-years (95% CI, 10.1-11.0) in those without (adjusted hazard ratio [HR], 1.15; 95% CI, 1.01-1.31). A history of gout was also associated with a higher risk of the other outcomes examined. Compared with placebo, dapagliflozin reduced the risk of the primary end point to the same extent in patients with (HR, 0.84; 95% CI, 0.66-1.06) and without a history of gout (HR, 0.79; 95% CI, 0.71-0.87; P = .66 for interaction). The effect of dapagliflozin use with other outcomes was consistent in participants with and without gout. Initiation of uric acid–lowering therapy (HR, 0.43; 95% CI, 0.34-0.53) and colchicine (HR, 0.54; 95% CI, 0.37-0.80) was reduced by dapagliflozin compared with placebo.Conclusions and RelevanceThis post hoc analysis of 2 trials found that gout was common in HF and associated with worse outcomes. The benefit of dapagliflozin was consistent in patients with and without gout. Dapagliflozin reduced the initiation of new treatments for hyperuricemia and gout.Trial RegistrationClinicalTrials.gov Identifiers: NCT03036124 and NCT03619213

This study aims to determine the relationship between social media marketing, brand awareness and purchasing decisions for somethinc products in the city of Padang, the population in this study was 150 with a sample of 150 respondents. Data obtained by conducting a questionnaire, then processed and tested using SmartPLS. From the research conducted, it is known that based on the results of hypothesis testing, it is known that directly social media marketing has a significant effect on brand awareness and social media marketing and brand awareness has a significant effect on purchasing decisions. And indirectly brand awareness has a role between social media marketing and purchasing decisions.

Background: Elderly is someone who is classified as old and is experiencing the aging process. The risk of falling and decreased function are two of the many geriatric syndromes, which are affected by various things, such as muscle weakness, imbalance, and poor posture. Objective: This study aimed to determine the difference in the effect of adding deep breathing exercises on postural training and only postural training on reducing the hyperkyphosis curve. Methods: This study is quasi-experimental with a pre-test and post-test group design, in which the thoracic kyphosis curve is measured with a flexible ruler. The total sample in this study was 22 people divided into two groups. Group 1 consisted of 11 people with the intervention given, namely postural training, and group 2 consisted of 11 people with the intervention given, namely postural training and deep breathing exercise. Results: Hypothesis testing I and II using the Paired sample t-test showed a value of p=0.000, with an average value before and after in group 1 of 54.17 ± 2.39 and 50.90 ± 2.43, while in group 2, it was 54.61 ± 2.07 and 50, 11±1.93. Furthermore, Hypothesis testing III used the Mann Whitney-u tried and obtained a value of p=0.000 with a difference in group 1 of 3.26 ± 0.57 and group 2 of 4.50 ± 0.41. Conclusion: There is a significant difference in effectiveness with the addition of breathing exercises in postural training and postural training alone in reducing the hyperkyphosis curve.

Background: How patient characteristics and outcomes vary according to the duration of heart failure (HF) is unknown in individuals with mildly reduced or preserved ejection fraction. We compared these, and the efficacy and safety of dapagliflozin, according to the time from diagnosis of HF in a prespecified analysis of the DELIVER trial (Dapagliflozin Evaluation to Improve the Lives of Patients With Preserved Ejection Fraction Heart Failure). Methods: HF duration was categorized as ≤6 months, >6 to 12 months, >1 to 2 years, >2 to 5 years, or >5 years. The primary outcome was the composite of worsening HF or cardiovascular death. The effect of treatment was examined by HF duration category. Results: The number of patients in each category was as follows: 1160 (≤6 months), 842 (>6 to 12 months), 995 (>1 to 2 years), 1569 (>2 to 5 years), and 1692 (>5 years). Patients with longer-duration HF were older and had more comorbidities with worse symptoms. The rate of the primary outcome (per 100 person-years) increased with HF duration: ≤6 months, 7.3 (95% CI, 6.3 to 8.4); >6 to 12 months, 7.1 (6.0 to 8.5); >1 to 2 years, 8.4 (7.2 to 9.7); >2 to 5 years, 8.9 (7.9 to 9.9); and >5 years, 10.6 (9.5 to 11.7). Similar trends were seen for other outcomes. The benefit of dapagliflozin was consistent across HF duration category: the hazard ratio for the primary outcome in the ≤6-month group was 0.67 (95% CI, 0.50 to 0.91); >6 to 12 months, 0.78 (0.55 to 1.12); >1 to 2 years, 0.81 (0.60 to 1.09); >2 to 5 years, 0.97 (0.77 to 1.22); and >5 years, 0.78 (0.64 to 0.96; P interaction =0.41). The absolute benefit was greatest in longest-duration HF; the number needed to treat for HF >5 years was 24 versus 32 for ≤6 months. Conclusions: Patients with longer-duration HF were older, had more comorbidities and symptoms, and had higher rates of worsening HF and death. The benefits of dapagliflozin were consistent across HF duration. Even patients with long-standing HF and generally mild symptoms are not stable, and it is not too late for such patients to benefit from a sodium–glucose cotransporter 2 inhibitor. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT03619213.

Pada tahun 2020, kanker menjadi penyebab kematian utama di dunia dan dalam kurung 5 tahun prevalensi kanker mengalami peningkatan di Indonesia. Kekurangan dari terapi kanker yaitu kurangnya selektif dalam mematikan sel kanker, sehingga dapat mematikan sel sehat maka dari itu pasien dapat merasakan efek samping yang cukup signifikan. Oleh karena itu, telah diteliti pencarian terapi alternatif dari daun pepaya. Tujuan dari artikel ini adalah mengetahui potensi daun pepaya sebagai antikanker. Artikel ilmiah yang dipublikasi 2010 – 2021 dari 2 database (Scopus dan PubMed) ditelaah dan didapatkan 38 artikel. Daun pepaya diketahui mengandung kandungan senyawa flavonoid, fenolat, steroid, alkaloid, terpenoid, fenolat, karotenoid, tannin, saponin, asam lemak, glikosida, glikosinalat, dan klorofil. Daun pepaya juga diketahui memiliki aktivitas antikanker terhadap kanker kulit, payudara, hepar, paru, pankreas, serviks, prostat, ovarium, mesothelioma, dan darah. Aktivitas antikanker daun pepaya dipengaruhi oleh karakteristik sel dan sampel uji. Pemilihan sel uji memengaruhi pengujian antiproliferasi, yaitu dengan doubling time yang singkat maka potensi antiproliferasi lebih tinggi. Kandungan senyawa pada daun pepaya memengaruhi aktivitas antikanker, dan perolehannya sangat berhubungan dengan pemilihan pelarut dan teknik ekstraksi yang tepat. Sistem penghantaran sampel dengan nanopartikel yang diformulasikan dengan daun pepaya juga membantu meningkatkan bioavaibilitas dari ekstrak daun pepaya, sehingga potensi antikanker meningkat.

Background: Black people have a higher incidence and prevalence of heart failure (HF) than White people, and once HF has developed, they may have worse outcomes. There is also evidence that the response to several pharmacologic therapies may differ between Black and White patients. Objectives: The authors sought to examine the outcomes and response to treatment with dapagliflozin according to Black or White race in a pooled analysis of 2 trials comparing dapagliflozin to placebo in patients with heart failure with reduced ejection fraction (DAPA-HF [Dapagliflozin and Prevention of Adverse Outcomes in Heart Failure]) and heart failure with mildly reduced ejection fraction/heart failure with preserved ejection fraction (DELIVER [Dapagliflozin Evaluation to Improve the Lives of Patients With Preserved Ejection Fraction Heart Failure]). Methods: Because most self-identified Black patients were enrolled in the Americas, the comparator group was White patients randomized in the same regions. The primary outcome was the composite of worsening HF or cardiovascular death. Results: Of the 3,526 patients randomized in the Americas, 2,626 (74.5%) identified as White and 381 (10.8%) as Black. The primary outcome occurred at a rate of 16.8 (95% CI: 13.8-20.4) in Black patients compared with 11.6 (95% CI: 10.6-12.7) per 100 person-years in White patients (adjusted HR: 1.27; 95% CI: 1.01-1.59). Compared with placebo, dapagliflozin decreased the risk of the primary endpoint to the same extent in Black (HR: 0.69; 95% CI: 0.47-1.02) and White patients (HR: 0.73 [95% CI: 0.61-0.88]; Pinteraction = 0.73). The number of patients needed to treat with dapagliflozin to prevent one event over the median follow-up was 17 in White and 12 in Black patients. The beneficial effects and favorable safety profile of dapagliflozin were consistent across the range of left ventricular ejection fractions in both Black and White patients. Conclusions: The relative benefits of dapagliflozin were consistent in Black and White patients across the range of left ventricular ejection fraction, with greater absolute benefits in Black patients.

BACKGROUND: Initiation and up-titration of guideline-directed medical therapies (GDMT) for heart failure with reduced ejection fraction (HFrEF) remains suboptimal, in part due to concerns regarding tolerability and adverse events (AE). OBJECTIVES: To compare rates of adverse events in patients randomized to GDMT medication vs placebo in a meta-analysis of landmark cardiovascular outcomes trials. METHODS: We assessed rates of reported AE in 17 landmark HFrEF clinical trials across each class of GDMT in the placebo and intervention arms. The overall rates of AE for each drug class, the absolute difference in frequency in AEs between the placebo and intervention arms, and the odds of each AE according based on randomization strata were calculated. RESULTS: AE were reported commonly in trials across each class of GDMT, with 75-85% of participants reporting at least one AE. There was no significant difference in the frequency of AE between the intervention and placebo arms, except for angiotensin converting enzyme (ACE) inhibitors (87.0% [85.0-88.8%] vs 82.0% [79.8-84.0%], absolute difference +5% with intervention, P

Aku Pintar adalah salah satu EdTech acuan yang bertujuan untuk meberdayakan ekosistem pendidikan dan meningkatkan kulaitas sumber daya manusia di Indonesia. Evaluasi kualitas sistem aplikasi Aku Pintar menjadi salah satu cara yang perlu dilakukan untuk menilai dan menguji tingkat kegunaan atau fungsionalitas dalam mengidentifikasi masalah secara spesifik pada sistem. Model pengukuran yang yang telah tervalidasi adalah ISO/IEC 25010 yang memiliki delapan indikator yang meliputi usability, portability, performance efficiency, functional suitability, maintainability, compatibility, reliability, dan security. Penelitian ini dilakukan dengan metode analisis data kuantitatif, uji validitas dan reliabilitas dengan menggunakan Statistical Package for the Social Sciences (SPSS). Metode sampel yang digunakan dalam penelitian ini adalah dengan metode simple random sampling dan dari perhitungal slovin dari jumlah pengguna aplikasi Aku Pintar populasi yang diambil sebanyak 100 responden. Hasil pengujian tingkat kualitas aplikasi dengan framework ISO/IEC 25010 model produuct quality didapatkan hasih layak dengan persentase berdasarkan yang terendah, 68% untuk indikator compatibility, indikator performance efficiency sebesar 71%, indikator security sebesar 74%, indikator realibility sebesar 75%, indikator maintanbility 81%, kemudian indikator funcitional suitibility dan usability memiliki persentase sama sebesar 82%, selanjutnya persentase terbesar portability sebesar 91%. Setelah didapatkan hasil persentase kualitas aplikasi Aku Pintar dibuat sebuah saran perbaikan untuk aplikasi agar kedepannya aplikasi lebih baik dalam meningkatkan kepuasan pengguna. Kata kunci : Aku Pintar, analisis, kualitas, iso/iec 25010, product quality

Eighteen nucleic acid therapeutics have been approved for treatment of various diseases in the last 25 years. Their modes of action include antisense oligonucleotides (ASOs), splice-switching oligonucleotides (SSOs), RNA interference (RNAi) and an RNA aptamer against a protein. Among the diseases targeted by this new class of drugs are homozygous familial hypercholesterolemia, spinal muscular atrophy, Duchenne muscular dystrophy, hereditary transthyretin-mediated amyloidosis, familial chylomicronemia syndrome, acute hepatic porphyria, and primary hyperoxaluria. Chemical modification of DNA and RNA was central to making drugs out of oligonucleotides. Oligonucleotide therapeutics brought to market thus far contain just a handful of first- and second-generation modifications, among them 2′-fluoro-RNA, 2′-O-methyl RNA and the phosphorothioates that were introduced over 50 years ago. Two other privileged chemistries are 2′-O-(2-methoxyethyl)-RNA (MOE) and the phosphorodiamidate morpholinos (PMO). Given their importance in imparting oligonucleotides with high target affinity, metabolic stability and favorable pharmacokinetic and -dynamic properties, this article provides a review of these chemistries and their use in nucleic acid therapeutics. Breakthroughs in lipid formulation and GalNAc conjugation of modified oligonucleotides have paved the way to efficient delivery and robust, long-lasting silencing of genes. This review provides an account of the state-of-the-art of targeted oligo delivery to hepatocytes.

Aims Ketone bodies (KB) are an important alternative metabolic fuel source for the myocardium. Experimental and human investigations suggest that KB may have protective effects in patients with heart failure. This study aimed to examine the association between KB and cardiovascular outcomes and mortality in an ethnically diverse population free from cardiovascular disease (CVD). Methods and results This analysis included 6796 participants (mean age 62 ± 10 years, 53% women) from the Multi-Ethnic Study of Atherosclerosis. Total KB was measured by nuclear magnetic resonance spectroscopy. Multivariable-adjusted Cox proportional hazard models were used to examine the association of total KB with cardiovascular outcomes. At a mean follow-up of 13.6 years, after adjusting for traditional CVD risk factors, increasing total KB was associated with a higher rate of hard CVD, defined as a composite of myocardial infarction, resuscitated cardiac arrest, stroke, and cardiovascular death, and all CVD (additionally included adjudicated angina) [hazard ratio, HR (95% confidence interval, CI): 1.54 (1.12–2.12) and 1.37 (1.04–1.80) per 10-fold increase in total KB, respectively]. Participants also experienced an 87% (95% CI: 1.17–2.97) increased rate of CVD mortality and an 81% (1.45–2.23) increased rate of all-cause mortality per 10-fold increase in total KB. Moreover, a higher rate of incident heart failure was observed with increasing total KB [1.68 (1.07–2.65), per 10-fold increase in total KB]. Conclusion The study found that elevated endogenous KB in a healthy community-based population is associated with a higher rate of CVD and mortality. Ketone bodies could serve as a potential biomarker for cardiovascular risk assessment.

A substantial proportion of patients with heart failure and kidney disease have poorly controlled blood pressures. This study aimed to evaluate patterns of blood pressure after initiation of an angiotensin receptor neprilysin inhibitor (ARNI) or an angiotensin-converting enzyme inhibitor (ACEI)/angiotensin receptor blocker (ARB) across the spectrum of kidney function.Between 2016 and 2020, we evaluated 26,091 patients admitted to a Veterans Affairs hospital for an acute heart failure exacerbation with reduced ejection fraction. We assessed patterns of systolic and diastolic blood pressure among those started on ARNI or ACEI/ARB over 6 months, overall and across estimated glomerular filtration rate (eGFR). To account for differential treatment factors, we applied 1:1 propensity score matching using 15 known baseline covariates.There were 13,781 individuals treated with an ACEI or ARB and 2589 individuals treated with an ARNI prescription. After propensity score matching, 839 patients were matched in each of the ARNI and ACEI/ARB groups. Mean baseline estimated glomerular filtration rate (eGFR) was 63.8 (standard deviation 21.6), and 10% had stage 4 or 5 chronic kidney disease. Patients in the ARNI group experienced greater systolic blood pressure reduction at month 3 (-5.2 mmHg vs -2.2 mmHg, ARNI vs ACEI/ARB; P0.001), and month 6 (-4.7 mmHg vs -1.85 mmHg, ARNI vs ACEI/ARB; P0.001). These differences in systolic blood pressure by 6 months did not vary by eGFR above and below 60 mL/min/1.73mThe use of ARNI was associated with significant reduction in blood pressure as compared to the ACEI/ARB group overall and across the eGFR spectrum, including in advanced chronic kidney disease.

This research work focuses on augmenting the power conversion efficiency of the polycrystalline silicon solar cell with the aid of antireflection coating (ARC) of synthesized molybdenum disulphide (MoS2). The sol-gel technique and electrospraying method were preferred for synthesizing and depositing MoS2 as transparent thin films on the surface of the solar cells. The optical, electrical, structural, and thermal properties of the coated solar cells were analyzed for understanding the influence of the MoS2 coating. Five different samples (A-II, A-III, A-IV, A-V, and A-VI) were coated with varying coating time. Among them, 120 min coated sample experienced a maximum power conversion efficiency (PCE) of 17.96% and 18.82% under direct sunlight and neodymium light with resistivity as low as 2.79 × 10 − 3 Ω − cm . The investigation of optical properties of the coated solar cells revealed a maximum transmittance of 93.6% and minimum reflectance of 6.3%, achieved for A-IV sample in the visible UV spectrum. Sample A-IV showed prominent results in the temperature analysis with temperatures as low as 38.9°C in uncontrolled and 43.2°C in controlled source environments. The results from various analyses proved that MoS2 was an appropriate material for an antireflection coating to enhance the performance of polycrystalline solar cell.

ImportanceThe expansion of sodium-glucose cotransporter-2 (SGLT-2) inhibitor use in patients with heart failure (HF) and left ventricular ejection fraction (LVEF) more than 40% following the EMPEROR-Preserved (Empagliflozin Outcome Trial in Patients with Chronic Heart Failure with Preserved Ejection Fraction) and the DELIVER (Dapagliflozin Evaluation to Improve the Lives of Patients with Preserved Ejection Fraction Heart Failure) trials have major implications in the US.ObjectiveTo quantify the estimated US population-level impact of reducing worsening HF events with SGLT-2 inhibitors in individuals with LVEF more than 40%.Design, Setting, and ParticipantsThis decision analytical model study used self-reported HF data from the National Health and Nutritional Examination Survey from 2015 to 2018, which was weighted across the entire US population and subsequently mapped onto newly eligible LVEF distributions from the Get With The Guidelines–Heart Failure registry. All patients older than 18 years with HF from the National Health and Nutritional Examination Survey were grouped into the following categories: all LVEF and LVEF more than 40%. Numbers needed to treat estimations over 3 years were obtained for outcome measures from the EMPEROR-Reduced (Empagliflozin Outcome Trial in Patients with Chronic Heart Failure with Reduced Ejection Fraction), EMPEROR-Preserved, DAPA-HF (Dapagliflozin and Prevention of Adverse Outcomes in Heart Failure), and DELIVER trials.Main Outcomes and MeasuresWorsening HF events (unplanned HF hospitalizations, urgent HF visits requiring intravenous therapy, or cardiovascular death).ResultsA projected 4 794 524 (95% CI, 3 997 363-5 591 684) adults (57% male; 67% White; mean age, 66 years) with HF would be eligible for SGLT-2 inhibitors. Of this total population, 2 619 248 (95% CI, 2 183 759-3 054 737) would be estimated as newly eligible with LVEF more than 40%. Based on estimates from the EMPEROR-Reduced/EMPEROR-Preserved and DAPA-HF/DELIVER trials, a projected 624 247 (95% CI, 520 457-728 037) to 627 124 (95% CI, 522 855-731 392) worsening HF events could be prevented across the LVEF spectrum with SGLT-2 inhibitors over 3 years, of which 232 589 (95% CI, 193 918-271 260) to 282 879 (95% CI, 235 846-329 912) events could be prevented in individuals with LVEF more than 40%. Moreover, an estimated 468 904 (95% CI, 390 942-546 867) to 499 110 (95% CI, 416 125-582 094) total HF hospitalizations could be prevented across the LVEF spectrum, of which 172 870 (95% CI, 144 128-201 613) to 231 018 (95% CI, 192 608-269 428) could be prevented in individuals with LVEF more than 40%.Conclusions and RelevanceIn addition to the proven benefit in HF with LVEF of 40% and less, optimal implementation of SGLT-2 inhibitor therapy for HF with LVEF more than 40% can potentially prevent/postpone an additional approximately 250 000 worsening HF events over 3 years in the US.

Purpose To determine if smartphone photography could be a useful adjunct to blindness prevalence surveys by providing an accurate diagnosis of corneal opacity. Methods A total of 174 patients with infectious keratitis who had undergone corneal culturing over the past 5 years were enrolled in a diagnostic accuracy study at an eye hospital in South India. Both eyes had an ophthalmologist-performed slit lamp examination, followed by anterior segment photography with a handheld digital single lens reflex (SLR) camera and a smartphone camera coupled to an external attachment that provided magnification and illumination. The diagnostic accuracy of photography was assessed relative to slit lamp examination. Results In total, 90 of 174 enrolled participants had a corneal opacity in the cultured eye and no opacity in the contralateral eye, and did not have a penetrating keratoplasty or missing photographs. Relative to slit lamp examination, the sensitivity of corneal opacity diagnosis was 68% (95%CI 58-77%) using the smartphone's default settings and 59% (95%CI 49-69%) using the SLR, and the specificity was 97% (95%CI 93-100%) for the smartphone and 97% (95%CI 92-100%) for the SLR. The sensitivity of smartphone-based corneal opacity diagnosis was higher for larger scars (81% for opacities 2 mm in diameter or larger), more visually significant scars (100% for eyes with visual acuity worse than 20/400), and more recent scars (85% for eyes cultured in the past 12 months). Conclusion The diagnostic performance of a smartphone coupled to an external attachment, while somewhat variable, demonstrated high specificity and high sensitivity for all but the smallest opacities.

Nonalcoholic fatty liver disease (NAFLD) is a leading cause of liver disease worldwide. The estimated global incidence of NAFLD is 47 cases per 1,000 population and is higher among males than females. The estimated global prevalence of NAFLD among adults is 32% and is higher among males (40%) compared to females (26%). The global prevalence of NAFLD has increased over time, from 26% in studies from 2005 or earlier to 38% in studies from 2016 or beyond. The prevalence of NAFLD varies substantially by world region, contributed by differing rates of obesity, and genetic and socioeconomic factors. The prevalence of NAFLD exceeds 40% in the Americas and South-East Asia. The prevalence of NAFLD is projected to increase significantly in multiple world regions by 2030 if current trends are left unchecked. In this review, we discuss trends in the global incidence and prevalence of NAFLD and discuss future projections.

BACKGROUND: Universal design (UD) is a beneficial concept for better accessible design to improve easy approachability and industry-standard products. Specifically, Indian household products require UD features in domains such as bathroom and toilet, furniture, kitchen utilities, and home appliances. Among household product design in India, a lack of understanding of the product’s universality might be a constraint for product designers. Also, there are no studies assessing the UD features of Indian household products. OBJECTIVE: (1) To examine the UD feature of Indian household products against the seven principles of UD; (2) To determine the most lacking UD feature among Indian household products; and (3) To find out the Indian household categories (i.e., bathroom and toilet, furniture, kitchen utilities, and home appliances) which are most lacking in UD performance. METHOD: The UD features were evaluated using a standardized questionnaire, which contains 29 questions on UD principles and general questions (gender, education level, age and house characteristics). Using statistical packages, the data were computed for mean and frequency distribution, as well as analyzed to achieve the objectives. The analysis of variance (ANOVA) was performed for comparative analyses. RESULTS: The results indicate that the “flexibility in use” and “perceptible information” principles were lacking among the Indian household products. Also, bathroom and toilet and furniture household products were most lacking in UD performance. CONCLUSION: The findings of this research will enlighten the insights into the usefulness, usability, safety, and marketability of Indian household products. In addition, they will be helpful in promoting UD features and obtaining financial benefits from the Indian market.

Nanotechnology has made a tremendous impact over a period of three decades in various facets of industrial and medical sectors and still find recent interests to exploit their characteristics for commercial applications. Nanobiotechnology is a field of using nanomaterials for biological applications. The preparation of nanomaterials from biological sources has been known as 'green' technology. Nanoparticles measure in the size range of 1-100 nm and possess unique characteristics than their bulk materials with potential applications in various biological, medical, industrial, agricultural and ecological fields. Using nanoparticles in antimicrobial applications has been explored since the early years of Nanotechnology development. However, few reports exist on the mechanisms of antimicrobial actions mediated by nanoparticles and their effects on environment and ecosystems. Several factors affect the antimicrobial properties of nanoparticles, which are quite important to understand the roles of their antimicrobial action. This review is aimed to discuss the antibacterial properties, the mechanisms and antimicrobial applications of Nanoparticles in medicine and allied areas. We have suggested that despite the several applications of nanomaterials, their production by biological methods and suitable applications also need to focus on the toxicity implications. Nanomaterial toxicity in the ecological niche is of significant concern and regulatory bodies should be organized to evaluate the successful use of nanomaterials for a wide variety of applications. The review significantly summarizes hot topics of interest in antibacterial activities, mode of action, biomedical applications of nanoparticles, their metabolic fate in vivo and toxicity effects in humans for further consideration of researches in Microbial Nanotechnology.

Background: Sodium-glucose cotransporter-2 inhibitors have emerged as a key pharmacotherapy in heart failure (HF) with both reduced and preserved ejection fraction. The benefit of other HF therapies may be modified by sex, but whether sex modifies the treatment effect and safety profile of sodium-glucose cotransporter-2 inhibitors remains unclear. Our analyses aim to assess the effect of sex on the efficacy and safety of dapagliflozin. Methods: In a prespecified patient-level pooled analysis of DAPA-HF (Dapagliflozin and Prevention of Adverse Outcomes in Heart Failure) and DELIVER (Dapagliflozin Evaluation to Improve the Lives of Patients With Preserved Ejection Fraction Heart Failure), clinical outcomes were compared by sex (including the composite of cardiovascular death or worsening HF events, cardiovascular death, all-cause death, total events [first and recurrent HF hospitalization and cardiovascular death], and Kansas City Cardiomyopathy Questionnaire scores) across the spectrum of left ventricular ejection fraction. Results: Of a total of 11 007 randomized patients, 3856 (35%) were women. Women with HF were older and had higher body mass index but were less likely to have a history of diabetes and myocardial infarction or stroke and more likely to have hypertension and atrial fibrillation compared with men. At baseline, women had higher ejection fraction but worse Kansas City Cardiomyopathy Questionnaire scores than men did. After adjustment for baseline differences, women were less likely than men to experience cardiovascular death (adjusted hazard ratio, 0.69 [95% CI, 0.60–0.79]), all-cause death (adjusted hazard ratio, 0.69 [95% CI, 0.62–0.78]), HF hospitalizations (adjusted hazard ratio, 0.82 [95% CI, 0.72–0.94]), and total events (adjusted rate ratio, 0.77 [95% CI, 0.71–0.84]). Dapagliflozin reduced the primary end point in both men and women similarly ( P interaction =0.77) with no sex-related differences in secondary outcomes (all P interaction >0.35) or safety events. The benefit of dapagliflozin was observed across the entire ejection fraction spectrum and was not modified by sex ( P interaction >0.40). There were no sex-related differences in serious adverse events, adverse events, or drug discontinuation attributable to adverse events. Conclusions: In DAPA-HF and DELIVER, the response to dapagliflozin was similar between men and women. Sex did not modify the treatment effect of dapagliflozin across the range of ejection fraction.

OBJECTIVE Epilepsy impacts 470,000 children in the United States. For patients with drug-resistant epilepsy (DRE) and unresectable seizure foci, vagus nerve stimulation (VNS) is a treatment option. Predicting response to VNS has been historically challenging. The objective of this study was to create a clinical VNS prediction tool for use in an outpatient setting. METHODS The authors performed an 11-year retrospective cohort analysis with 1-year follow-up. Patients < 21 years of age with DRE who underwent VNS (n = 365) were included. Logistic regressions were performed to assess clinical factors associated with VNS response (≥ 50% seizure frequency reduction after 1 year); 70% and 30% of the sample were used to train and validate the multivariable model, respectively. A prediction score was subsequently developed. Sensitivity, specificity, and area under the receiver operating characteristic curve (AUC) were calculated. RESULTS Variables associated with VNS response were < 4-year epilepsy duration before VNS (p = 0.008) and focal motor seizures (p = 0.037). The variables included in the clinical prediction score were epilepsy duration before VNS, age at seizure onset, number of pre-VNS antiseizure medications, if VNS was the patient’s first therapeutic epilepsy surgery, and predominant seizure semiology. The final AUCs were 0.7013 for the "fitted" sample and 0.6159 for the "validation" sample. CONCLUSIONS The authors developed a clinical model to predict VNS response in a large sample of pediatric patients treated with VNS. Despite the large sample size, clinical variables alone were not able to accurately predict VNS response. This score may be useful after further validation, although its predictive ability underscores the need for more robust biomarkers to predict treatment response.

Glycol nucleic acid (GNA) is an acyclic nucleic acid analog connected via phosphodiester bonds. Crystal structures of RNA–GNA chimeric duplexes indicated that nucleotides of the right-handed (S)-GNA were better accommodated in the right-handed RNA duplex than were the left-handed (R)-isomers. GNA nucleotides adopt a rotated nucleobase orientation within all duplex contexts, pairing with complementary RNA in a reverse Watson–Crick mode, which explains the inabilities of GNA C and G to form strong base pairs with complementary nucleotides. Transposition of the hydrogen bond donor and acceptor pairs using novel (S)-GNA isocytidine and isoguanosine nucleotides resulted in stable base-pairing with the complementary G and C ribonucleotides, respectively. GNA nucleotide or dinucleotide incorporation into an oligonucleotide increased resistance against 3′-exonuclease-mediated degradation. Consistent with the structural observations, small interfering RNAs (siRNAs) modified with (S)-GNA had greater in vitro potencies than identical sequences containing (R)-GNA. (S)-GNA is well tolerated in the seed regions of antisense and sense strands of a GalNAc-conjugated siRNA in vitro. The siRNAs containing a GNA base pair in the seed region had in vivo potency when subcutaneously injected into mice. Importantly, seed pairing destabilization resulting from a single GNA nucleotide at position 7 of the antisense strand mitigated RNAi-mediated off-target effects in a rodent model. Two GNA-modified siRNAs have shown an improved safety profile in humans compared with their non-GNA-modified counterparts, and several additional siRNAs containing the GNA modification are currently in clinical development.

Hepatic steatosis is a recognised risk factor for cardiovascular disease (CVD). However, its effect on patient outcomes following acute myocardial infarction (AMI) remains poorly understood. This study examines the prevalence and prognosis of hepatic steatosis and fibrosis in post-AMI patients.Patients presenting with AMI to a tertiary hospital were examined from 2014 to 2021. Hepatic steatosis and advanced hepatic fibrosis were determined using hepatic steatosis index and fibrosis-4 index respectively. The primary outcome was all-cause mortality. Cox regression models identified determinants of mortality after adjustments and Kaplan-Meier curves were constructed for all-cause mortality, stratified by hepatic steatosis and advanced fibrosis.Of 5,765 patients included, 24.8% had hepatic steatosis, of whom 41.7% were diagnosed with advanced fibrosis. The median follow-up duration was 2.7 years. Patients with hepatic steatosis tended to be younger, female, with elevated BMI and increased metabolic burden of diabetes, hypertension and hyperlipidemia. Patients with hepatic steatosis (24.6% vs 20.9% mortality, p0.001) and advanced fibrosis (45.6% vs 32.9% mortality, p0.001) had higher all-cause mortality rates compared to their respective counterparts. Hepatic steatosis (aHR 1.364, 95%CI 1.145-1.625, p=0.001) was associated with all-cause mortality after adjustment for confounders. Survival curves demonstrated excess mortality in patients with hepatic steatosis compared to those without (p=0.002).Hepatic steatosis and advanced fibrosis have a substantial prevalence among patients with AMI. Both are associated with mortality, with incrementally higher risk when advanced fibrosis ensues. Hepatic steatosis and fibrosis could help risk stratification of AMI patients beyond conventional risk factors. This article is protected by copyright. All rights reserved.