Class 2A Research Articles

Analysis of safety and outcome of use of NOAC in intracardiac thrombi over warfarin

Abstract Introduction Intracardiac clots occur in 15- 25% of patients post myocardial infarction and in patient with atrial fibrillation. It holds poor outcome if not treated with anticoagulation. Warfarin remains the drug of choice in such patients, however recently according to the newly published data, the European Society of Cardiology (ESC) has recommended non-vitamin K antagonist anticoagulant (NOAC) for intracardiac clots as a class 2A recommendation. There is no documented data in the region of the gulf regarding the use of NOAC in intracardiac clots. Aim We aim in this study to evaluate the use of NOAC in the treatment of intracardiac clots over warfarin, by studying the effectiveness, safety and associated complications. Methodology A retrospective cohort study from April 2017 to December 2023 was conducted of patient’s above 18 years old who have a documented intracardiac clot on echocardiography. The patient were grouped into patients discharged on NOAC and those discharged on warfarin. The participants were studied for resolution of clot and development of complication; death, bleeding and thrombosis. Results A total of 253 patients fulfilled the inclusion criteria. Out of which 45 ( 18%) patients were discharged on NOAC and 208 (82%) on warfarin. The two groups had similar demographics with equally mean age of 71 years old , 89% being males, 38% hypertensive and most common clot in the left ventricle in both groups. From those patients with documented follow up ( NOAC 45% average of 8 months, Warfarin 62% average of 7 months); 48% in the NOAC group had a documented resolution of the clot while 44% in the warfarin group had a documented resolution of the intracardiac clot.(p value of 0.7) The median resolution time in the NOAC group was 4 months while in the warfarin group 3.5 months. Bleeding occurred in 19% and mortality rate was 5% in NOAC group, while in the warfarin group 10% developed bleeding and mortality rate was 6%. Conclusion Our data pointed out the safety of NOAC as a reasonable alternative to warfarin inpatient with intracardiac clots emphasizing the ESC recommendation in this regards. We recommend a randomized studies to prove the superiority of NOAC as anticoagulation of choice in intracardiac thrombi.

Influence of Asparaginase on Acrylamide Content, Color, and Texture in Oat, Corn, and Rice Cookies.

The safety of cereal-based baked goods can be compromised by acrylamide, a processing contaminant and class 2A carcinogen. One method to prevent acrylamide formation is by converting asparagine to aspartic acid using asparaginases. Four different asparaginases were tested using two dough incubation temperatures and dosages for oat, corn, and rice cookies. To evaluate the impact of asparaginases on product quality, color and texture were measured. Acrylamide was reduced by up to 97, 95, and 92% for oat, corn, and rice cookies, respectively, compared to the control. Asparaginase treatment resulted in minor changes in color and texture. There was a strong correlation between acrylamide concentrations in cookies and the free asparagine content of the flour. By minimizing the formation of acrylamide while maintaining product quality, the use of asparaginases offers a promising approach to enhancing food safety standards and protecting public health, potentially influencing regulatory guidelines and consumer preferences.

High Salt-Resistant Urethanase Degrades Ethyl Carbamate in Soy Sauce.

Urethanase is a promising biocatalyst for degrading carcinogen ethyl carbamate (EC) in fermented foods. However, their vulnerability to high ethanol and/or salt and acidic conditions severely limits their applications. In this study, a novel urethanase from Alicyclobacillus pomorum (ApUH) was successfully discovered using a database search. ApUH shares 49.4% sequence identity with the reported amino acid sequences. It belongs to the Amidase Signature family and has a conserved "K-S-S" catalytic triad and the characteristic "GGSS" motif. The purified enzyme overexpressed in Escherichia coli exhibits a high EC affinity (Km, 0.306 mM) and broad pH tolerance (pH 4.0-9.0), with an optimum pH 7.0. Enzyme activity remained at 58% in 12% (w/v) NaCl, and 80% in 10% (v/v) ethanol or after 1 h treatment with the same ethanol solution at 37 °C. ApUH has no hydrolytic activity toward urea. Under 30 °C, the purified enzyme (200 U/L) degraded about 15.4 and 43.1% of the EC in soy sauce samples (pH 5.0, 6.0), respectively, in 5 h. Furthermore, the enzyme also showed high activity toward the class 2A carcinogen acrylamide in foods. These attractive properties indicate their potential applications in the food industry.

Predicting adjuvant radiation therapy benefit in cutaneous squamous cell carcinoma with the 40-gene expression profile.

Aim: To independently confirm that the 40-gene expression profile (40-GEP) test can identify patients with high-risk cutaneous squamous cell carcinoma who are more or less likely to benefit from adjuvant radiation therapy (ART).Materials & methods: Primary cutaneous squamous cell carcinoma tumors from two academic centers received retrospective 40-GEP testing and were analyzed for 5-year metastasis-free survival and projected time to event.Results: Random sampling of matched patient pairs (n=52 ART-treated; 371no ART) showed a median 50% decrease in 5-year progression rate for ART-treated patients (vs no ART) with 40-GEP Class 2B. Class 2A was associated with a modest ART benefit, but not Class 1.Conclusion: The 40-GEP identified patients most likely to benefit from ART (Class 2B) and those that can consider deferring treatment (Class 1).

Italian survey on the effectiveness of halotherapy administered via the Aerosal® system.

Over the years, halotherapy (HT) has shown promise in the treatment of respiratory and dermatological diseases. However, its widespread acceptance remains limited due to the absence of official guidelines and awareness among doctors and patients. Among the patented systems of administration of HT, Aerosal® is the only one consisting of 3 certified elements, all classified as Medical Devices Class 2A: a dry saline dispenser called Aerosalmed®, a 30 g salt dose named AeroNaCL®, and a confined environment in marine multilayered construction with walls coated in salt called Aerosal®. We conducted an online survey of subjects undergoing Aerosal® HT across 80 Italian centers. Participants provided demographic data, reasons for choosing HT, and perceptions of its effectiveness. Following 10 treatment sessions, they rated improvements in various aspects, such as skin condition, sleep quality, relaxation, and respiratory benefits. Most participants learned about HT through word of mouth rather than medical advice, suggesting a discrepancy between patient satisfaction and medical endorsement. Over 92% reported resolution of their health issues post-treatment, with significant improvements in sleep quality and relaxation, particularly in adults. The therapy showed promise in various conditions, including respiratory and skin disorders, possibly attributed to stress reduction and intrinsic therapeutic effects. Despite skepticism, HT administered through the Aerosal® system has shown therapeutic potential. The psycho-physical benefits observed in patients advocate for greater consideration of this therapy by clinicians, emphasizing its safety, tolerability, and absence of notable side effects. In this context, standardized systems like Aerosal® are crucial for ensuring treatment safety and efficacy.

Crystal structure of urethanase from Candida parapsilosis and insights into the substrate-binding through in silico mutagenesis and improves the catalytic activity and stability

Ethyl carbamate (EC) is classified as a Class 2A carcinogen, and is present in various fermented foods, posing a threat to human health. Urethanase (EC 3.5.1.75) can catalyze EC to produce ethanol, CO2 and NH3. The urethanase (cpUH) from Candida parapsilosis can hydrolyze EC, but its low affinity and poor stability hinder its application. Here, the structure of cpUH from Candida parapsilosis was determined with a resolution of 2.66 Å. Through sequence alignment and site-directed mutagenesis, it was confirmed that cpUH contained the catalytic triad Ser-cisSer-Lys of the amidase family. Then, the structure-oriented engineering mutant N194V of urethanase was obtained. Its urethanase activity increased by 6.12 %, the catalytic efficiency (kcat/Km) increased by 21.04 %, and the enzyme stability was also enhanced. Modeling and molecular docking analysis showed that the variant N194V changed the number of hydrogen bonds between the substrate and the catalytic residue, resulting in enhanced catalytic ability. MD simulation also demonstrated that the introduction of hydrophobic amino acid Val reduced the RMSD value and increased protein stability. The findings of this study suggest that the N194V variant exhibits significant potential for industrial applications due to its enhanced affinity for substrate binding, improved catalytic efficiency, and increased enzyme stability.

Immuno-targeting the ectopic phosphorylation sites of PDGFRA generated by MAN2A1-FER fusion in HCC.

HCC is one of the most lethal cancers for humans. Mannosidase alpha class 2A member 1 (MAN2A1)-FER is one of the most frequent oncogenic fusion genes in HCC. In this report, we showed that MAN2A1-FER ectopically phosphorylated the extracellular domains of PDGFRA, MET, AXL, and N-cadherin. The ectopic phosphorylation of these transmembrane proteins led to the activation of their kinase activities and initiated the activation cascades of their downstream signaling molecules. A panel of mouse monoclonal antibodies was developed to recognize the ectopic phosphorylation sites of PDGFRA. The analyses showed that these antibodies bound to the specific phosphotyrosine epitopes in the extracellular domain of PDGFRA with high affinity and specificity. The treatment of MAN2A1-FER-positive cancer HUH7 with one of the antibodies called 2-3B-G8 led to the deactivation of cell growth signaling pathways and cell growth arrest while having minimal impact on HUH7ko cells where MAN2A1-FER expression was disrupted. The treatment of 2-3B-G8 antibody also led to a large number of cell deaths of MAN2A1-FER-positive cancer cells such as HUH7, HEPG2, SNU449, etc., while the same treatment had no impact on HUH7ko cells. When severe combined immunodeficiency mice xenografted with HEPG2 or HUH7 were treated with monomethyl auristatin E-conjugated 2-3B-G8 antibody, it slowed the progression of tumor growth, eliminated the metastasis, and reduced the mortality, in comparison with the controls. Targeting the cancer-specific ectopic phosphorylation sites of PDGFRA induced by MAN2A1-FER may hold promise as an effective treatment for liver cancer.

Evaluation of Science Implementation in Mechanical Engineering Design Curriculum Class 2A State Polytechnic of Jakarta Pekalongan City Campus Academic Year 2023/2024

Evaluation of Science Implementation in Mechanical Engineering Design Curriculum Class 2A State Polytechnic of Jakarta Pekalongan City Campus Academic Year 2023/2024

#2613 Clinical spectrum and prognosis of the atypical polycystic kidney disease caused by monoallelic loss-of-function IFT140 variants

Abstract Background and Aims Monoallelic loss-of-function (LoF) variants in IFT140, which protein product is involved in retrograde ciliary trafficking and ciliary entry of membrane protein, have been recently linked to ADPKD spectrum, with 44 pedigrees reported so far [1]. The aim of this study was to characterize the disease presentation and renal outcome of individuals with monoallelic LoF variants of IFT140. Method Clinical information, family history and imaging data were collected for individuals with LoF IFT140-variants identified amongst 2800 individuals recruited in the Genkyst and Cystic ADPKD patients cohorts, and in different French, Spanish, and German centers. Targeted massive parallel sequencing of cystic genes or whole exome sequencing was performed. Newly identified and recently reported cases were combined to evaluate the influence of sex on eGFR using linear regression taking age into account. In addition, data of the Genome Aggregation (GnomAD) v4.0 and of the 100k Genomes project were respectively used to explore genetic prevalence and disease penetrance and expressivity. Results A total of 75 individuals from 61 pedigrees were identified (median age at last follow-up 56 years, 52% females). Forty-one different LoF IFT140-variants were identified: 14 nonsense, 7 splice-site, 14 frameshifting deletions or insertions and 6 large deletions, and no additional pathogenic variant was identified in any other gene. A majority of the individuals presented with large, exophytic cysts, median total kidney volume 688 (n = 35, range 201-4139) ml, and 90.9% were classified in Mayo Class 2A. Although 70.4% of the individuals had stage 1 or 2 chronic kidney disease (CKD) at the last follow up, proportion of CKD stage 3-5 was significantly higher (56.3% vs 7.7%, p < 0.00001) after 60 years of age. Adjusted for age, males exhibited lower eGFR (linear regression, p = 0.038, Fig. 1). Median age at diagnosis of hypertension was 63 years. Liver cysts were present in 12% of affected individuals with no case of symptomatic polycystic liver disease, and intracranial aneurysms in three of 10 screened patients. The genetic prevalence of monoallelic LoF IFT140 variants was estimated to be 19.56 (0.95 CI 18.60-20.53) per 10,000 in the entire GnomAD population (n = 280 in 807,162) and 29.4 (0.95 CI 25.4-33.8) per 10,000 in the 100kG (n = 190 in 64,185). Amongst the latter, kidney cysts were reported in 26.8% and diagnosis cystic kidney disease (Q61) was established in 18.4%. No obvious extra renal manifestations were identified, and out of total of 730 phenotype association tests conducted, only Q61 was associated with pLOF IFT140 variants (p = 2.9 × 10−9, OR = 5.6 (3.3-9.2)). Conclusion Individuals with monoallelic LoF variants of IFT140 are likely to develop kidney cysts and/or atypical forms of ADPKD. However, a large proportion may remain asymptomatic or undiagnosed. There is no evidence to recommend cascade screening using genetic testing in young at risk relatives. Follow-up of blood pressure and eGFR after 50 years of age should be advised.

Association of a 40-Gene Expression Profile With Risk of Metastatic Disease Progression of Cutaneous Squamous Cell Carcinoma and Specification of Benefit of Adjuvant Radiation Therapy

PurposeAdjuvant radiation therapy (ART) for cutaneous squamous cell carcinoma (cSCC) is recommended based on a number of wide-ranging clinicopathologic features, which encompass a broad array of patients. The 40-gene expression profile (40-GEP) test classifies cSCC tumors into low (Class 1) or higher (Class 2A) or highest (Class 2B) risk of nodal and/or distant metastasis. This study's hypotheses are 1) local recurrence is associated with metastatic disease progression, and 2) 40-GEP, by identifying high risk for metastasis, could predict a metastasis-specific benefit from ART. MethodsSamples were obtained from 920 patients (ART-untreated: 496 Class 1, 335 Class 2A, 33 Class 2B; ART-treated: 11 Class 1, 35 Class 2A, 10 Class 2B) who were matched on clinical risk factors and stratified by ART status, to create 49 matched patient strata. To control for the variety of characteristics and treatment selection bias, randomly sampled pairs of matched ART and non-ART patients comprising 10,000 resampled cohorts were each analyzed for 5-year metastasis-free survival and predicted time to metastatic event. ResultsOf 96 patients experiencing local recurrence, 56.3% experienced metastasis; of those experiencing both, 88.9% had local recurrence before (75.9%) or concurrently (13.0%) with metastasis. After matching for clinicopathological risk, median 5-year disease progression rates for resampled cohorts demonstrated approximately 50% improvement for Class 2B ART-treated as compared to ART-untreated cohorts. Class 2B ART-treated cohorts had a 5-fold delay in predicted time to metastatic event and deceleration of disease progression as compared to ART-untreated cohorts (Kolmogorov-Smirnov test, p<0.01); this was not observed for Class 1 or 2A patients (p>0.05 for each). No risk factor or staging system combined with ART status identified groups that would benefit from ART as well as 40-GEP. Conclusion40-GEP identifies patients at highest risk of nodal/distant metastasis who may derive greatest benefit from ART, as well as patients who may have clinical indications for ART but are at low risk of metastasis. Compared to current guidelines, 40-GEP could provide greater specificity concerning the benefit of ART in individual patients.

Integrating the 40-Gene Expression Profile (40-GEP) Test Improves Metastatic Risk-Stratification Within Clinically Relevant Subgroups of High-Risk Cutaneous Squamous Cell Carcinoma (cSCC) Patients.

The validated 40-gene expression profile (40-GEP) test independently stratifies risk of regional or distant metastasis for cutaneous squamous cell carcinoma (cSCC) tumors with high-risk clinicopathologic features. This study evaluated the stratification of risk by the 40-GEP test in a large cohort of tumors with one or more high-risk factors and in clinically relevant subgroups, including tumors within National Comprehensive Cancer Network (NCCN) high- and very-high-risk groups, lower-stage BWH T1 and T2a tumors, and patients > 65years old. This multicenter (n = 58) performance study of the 40-GEP included 897 patients. Kaplan-Meier analyses were performed to assess risk stratification profiles for 40-GEP Class 1 (low), Class 2A (higher) and Class 2B (highest) risk groups, while nested Cox regression models were used to compare risk prediction of clinicopathologic risk classification systems versus risk classification systems in combination with 40-GEP. Patients classified as 40-GEP Class 1, Class 2A, or Class 2B had significantly different metastatic risk profiles (p < 0.0001). Integrating 40-GEP results into models with individual clinicopathologic risk factors or risk classification systems (Brigham and Women's Hospital, American Joint Committee on Cancer Staging Manual, 8th Edition) and NCCN demonstrated significant improvement in accuracy for prediction of metastatic events (ANOVA for model deviance, p < 0.0001 for all models). The 40-GEP test demonstrates accurate, independent, clinically actionable stratification of metastatic risk and improves predictive accuracy when integrated into risk classification systems. The improved accuracy of risk assessment when including tumor biology via the 40-GEP test ensures more risk-aligned, personalized patient management decisions.

Considering the impact of shift working on health.

Shift work is necessary for the provision of health services, especially in hospitals as it is the only way to provide continuous care to patients. Working at night is inconsistent with the body's biological clock and night shift working hugely disrupts the circadian and sleep wake cycles. In 2020, the World Health Organization classified night shift working as being a 'probable' class 2A carcinogen and a number of independent cohort studies of both night workers and shift workers have observed increased incidence of certain cancers. Altered sleep timing, food timing and light exposure typical for shift workers leads to an acute circadian disruption and misalignment of regulatory hormones. This straying from synchronisation has been shown to result in individuals being more vulnerable to a number of chronic health conditions. Night shift work disrupts the normal sleep-wake cycle, often leading to shortened sleep duration and excessive fatigue and the results of this are far reaching. This article will explore the full impact of shift working, questioning if current practices employed within the NHS should continue.

Use of the 40-Gene Expression Profile (40-GEP) Test in Medicare-Eligible Patients Diagnosed with Cutaneous Squamous Cell Carcinoma (cSCC) to Guide Adjuvant Radiation Therapy (ART) Decisions Leads to a Significant Reduction in Healthcare Costs

Objective: Adjuvant radiation therapy (ART) is often recommended for high-risk cSCC patients but carries significant costs and risks. This study aims to determine if utilizing the 40-GEP test to guide ART can reduce healthcare costs in cSCC management. Methods: Medical claims data with new diagnoses of cSCC for the 12 months ending June 2022 in the Medicare (≥65 years) population (source: IQVIA claims database) were obtained and normalized to the general population for missingness. CPT codes associated with radiation therapy within one-year post diagnosis were used to establish adjuvant RT use (defined as ‘ART’). Average weighted direct costs for four major ART modalities were calculated from published studies and (IQVIA). Sensitivity analysis was used to assess the financial impact of ART treatment using varying distributions of 40-GEP Class results. Results: Normalized medical claims data identified 22,917 Medicare-eligible cSCC patients who received ART within the United States. The weighted average direct cost for ART, which includes the four most used CPT code-defined modalities (IGRT, IMRT, IMPT, and XRT), was $60,693 per patient, amounting to an annual projected ART cost of $1.4 billion. Using the distribution of 40-GEP results from published studies, utilization of a 40-GEP test result to avoid ART in these patients could save up to $972 million in Medicare-eligible population. Sensitivity analysis shows, depending upon the distribution of the 40-GEP results, that for every 10% of Class 2A test results omitting ART, an extra $38-66 million in annual savings is expected Limitations: Potential limitations include a need for more comprehensive patient information and the cost of ART-related complications. Conclusion: Utilizing the 40-GEP test results to guide ART decision-making would result in material savings to Medicare.

A ratiometric fluorescent “off-on” sensor for acrylamide detection in toast based on red-emitting copper nanoclusters stabilized by bovine serum albumin

Acrylamide, as a Class 2A carcinogen, poses serious threats to human health. To achieve rapid and accurate determination of acrylamide in food, a ratiometric fluorescent “off–on” sensor was designed by incorporating red-emitting copper nanoclusters and glutathione. Copper nanoclusters with bimodal emission at 395 nm and 650 nm (excited at 310 nm) were synthesized by using bovine serum albumin as the ligand and ascorbic acid as the reductant. With glutathione addition, the fluorescence intensity at 650 nm gradually decreased, while the case at 395 nm slightly increased. The quenched fluorescence at 650 nm was subsequently restored by acrylamide through thiol-ene Michael addition reaction between acrylamide and glutathione. The constructed sensor showed excellent performance towards acrylamide detection in the range of 5–300 μM with a detection limit of 1.48 μM, and was further applied to real-sample detection of acrylamide in toast and exhibited good recoveries (90.29–101.30 %), indicating potential applications of this sensor.

Analysis of Students' Listening Anxiety in English as EFL Learners (A Case Study at the 2nd Semester of English Education Department in the State Islamic University Sultan Maulana Hasanuddin Banten

Listening is a complex processing in which the listeners take the incoming data, an acoustic signal, and interprets it based on a wide variety of linguistic and non-linguistic knowledge. The objective of this research is to find out the factors causes students’ listening anxiety in English as EFL learners at the 2nd Semester of English Education Department in the State Islamic University Sultan Maulana Hasanuddin Banten. This research used a descriptive qualitative method. The participants of this research were 28 students in class 2A. The instrument which is used in this research were observation, questionnaire and interview. The result of this research show that in the listening material factors, the students’ listening anxiety was caused by the speed rate, it is showed from 28 students there are 89,3% chose strongly agree with the statement. In lectures’ factors, the students’ listening anxiety caused by the lecturer show their frustration if the students do not know the answer, it is showed from 28 students there are 32,1% chose strongly agree with the statement. The last, in the students’ factors, the students listening anxiety caused by the environment around the student, if the environment around them is noisy they would distract and will missed the important point, it is showed from 28 students there are 50% students chose strongly agree with the statement. It can be concluded that the listening material factors are the most influential factors causing students' listening anxiety. The next influential factors are student factors, followed by lecturer factors.&#x0D;

UPAYA MENINGKATKAN HASIL BELAJAR SISWA KELAS 2A MI MASYHUDIYAH PADA MUATAN MATEMATIKA MELALUI PENERAPAN MODEL PEMBELAJARAN CONTEXTUAL TEACHING AND LEARNING

This research aims to find out how the application of the contextual teaching and learning model can improve learning outcomes in mathematics content regarding sides, angles and edges of geometric shapes in class 2A MI Masyhudiyah students. This type of research is classroom action research or PTK. This research design uses the Kemmis and Mc. Taggart model which consists of 4 components, namely planning, implementing actions, observing and reflecting. The research subjects that will be used in this classroom action research are 25 students in class 2A MI Mashhudiyah, consisting of 15 male students and 10 female students. Data collection techniques in this research used interviews, observation and tests. This research data analysis technique uses quantitative descriptive. The criteria for success in this classroom action research are based on increasing student learning outcomes in each cycle. The criteria used to see the success of the action are in the form of increasing student learning outcomes. Students are declared to have improved if a minimum percentage of 70% of all students meet the KKM score of 70. The results of the research show that student learning completeness in the pre-test was 8% with an average score of 43.2%, then in cycle 1 it was 56% with an average score -an average of 68.8 and in the second cycle it was 64% with an average value of 69.2 then in the post test of third cycle it was 80% with an average value of 75. From these data it clearly shows that student learning outcomes have increased and indicators of success have been achieved

Risk-Stratification using the 40-Gene Expression Profile (40-GEP) Test Identifies Patients with Node Negative Cutaneous Squamous Cell Carcinoma (cSCC) at Higher Risk of Metastasis Who May Benefit from Adjuvant Radiation Therapy (ART)

ART is a standard treatment used to reduce the risk of metastasis and recurrence in moderate‒to‒high-risk cSCC patients. Indications for ART have been largely based on pathologic risk factors and informed by staging systems, and while radiation oncologists generally designate a >10% risk threshold for usage of ART, there is no consensus on which groups of tumors may benefit from ART. The 40-GEP test has been independently validated to predict a cSCC patient's risk for regional/distant metastasis in patients with one or more high-risk clinicopathologic factors and reports three biologic risk groups: Class 1 (low, ∼7%), Class 2A (moderate, 20-25%), and Class 2B (high risk, >50%) for metastasis. This study aims to evaluate whether a biomarker informed risk stratification approach using a 40-GEP result could refine the ability to select patients with node negative cSCC at higher risk of metastasis who are most likely to benefit from ART. In this retrospective study, all patients had primary cSCC tissue with verified clinicopathologic information of tumors with one or more high-risk factors, met clinical testing criteria, were comprehensively staged, and had outcomes data (n = 954). Patients with node positive disease, or those with nodal failure within 3 months of diagnosis were excluded (n = 19). From the n = 935, an intermediate risk population wherein ART is often considered was defined as Brigham and Women's Hospital (BWH) ≥T2a (n = 489). Kaplan-Meier survival analysis and log-rank test were used to assess metastasis free survival (MFS). Univariate Cox regression compared metastasis rates between 40-GEP results. The 3-year MFS rate for this eligible for ART cohort was 82.4% The 40-GEP demonstrated statistically significant risk stratification with MFS rates of 92.4%, 76.1% and 59.4% for Class 1, Class 2A and Class 2B, respectively (p<0.0001). Cox regression was significant for Class 2A and 2B compared to Class 1, with a 3.2-fold and 6.4-fold increase in metastasis, respectively (p<0.0001). 64% (59/92) of all metastases received a Class 2A result, and 44% (14/32) of Class 2B patients metastasized. 46% (223/489) of the cohort received a Class 1 result. Of patients staged BWH T1 (n = 446), those with a Class 2A and 2B had an 88.7% and 66.7% MFS rate, respectively. Within this eligible for ART population, patients with Class 2A or 2B 40-GEP results have inferior rates of MFS, while Class 1 patients have <10% risk of metastasis. Nearly half of this population received a 40-GEP Class 1 result and could be considered for treatment de-intensification trials. Conversely, patients with low-risk BWH T1 stage, who are traditionally not considered for ART, that received a Class 2A or 2B (>10% risk of metastasis) could be considered for adjuvant therapy.

Media Product of Let's Memorize Anima Film to Improve the Ability to Memorize Daily Prayers

Background. This study aims to determine the use of animated film media products let's memorize to improve the ability to memorize daily prayers. Because this research is motivated by the lack of interesting learning media in memorizing daily prayers Purpose. This study uses a research approach of Research and Development (R&amp;D). Method. In this study the population was class 2A students of SDN 2 CITALANG, and the sample taken consisted of 15 students. Results. , Thus, judging from the results of student research. Conclusion. it is effective by using animated films let's memorize in improving the memorization ability of class 2A students of SDN 2 CITALANG.

RNA damage: the forgotten target of clinical compounds

Unlike DNA, RNA can be found in every sub-cellular compartment, where it is used to impart the genetic code or perform essential catalytic activities. As a result, damage to RNA is more spatially pervasive than damage to DNA and can have profound effects on gene expression and RNA-dependent activities. The past decade has seen the pathways involved in detecting and responding to damage of specific RNAs defined. These studies largely used high concentrations of tool compounds or deletion of essential factors for the response to RNA damage to study its effects. RNA is damaged by both endogenous and exogenous agents, with the effect of exogenous agents administered as therapeutics the focus of this review. In an effort to formalise studies into clinical RNA damage biology we propose 4 types of RNA damaging drug that we divide into 2 broad classes. Class 1 drugs result from synthesis using non-canonical nucleotides, which are incorporated into RNA in place of the canonical nucleotides. This class is subdivided depending on the outcome of this misincorporation on the nascent transcript. Class 2 drugs result in covalent ligation of moieties that alter RNA structure. This class is subdivided according to the functionality of the covalent ligation—class 2a are monovalent while class 2b are divalent. We discuss the evidence for and mechanisms of RNA damage as well as highlighting the unknown factors that require further investigation to determine the molecular mechanisms of these drugs.

Development and Validation of a Simple and Sensitive ICP-MS Method for the Quantification of Elemental Impurities in Propafenone Hydrochloride Drug Substance

Elemental impurities are substances present in drug products, excipients, or drug formulations. They may be formed by the presence of catalysts and environmental contaminants. Elemental impurities can be detected by a sophisticated method such as Inductively Coupled Plasma Mass Spectrometry (ICP–MS). ICP-MS is an advanced method to detect elemental impurities in drug substances. In this study Propafenone hydrochloride drug was used, Propafenone Hydrochloride is an antiarrhythmic medication belonging to class 1C used to prevent supraventricular and ventricular arrhythmias. The present study was aimed to develop and validate inductively coupled plasma mass spectroscopic (ICP–MS) method for detection of elemental contaminants, i.e., Class 1, Cd, Pb, As, Class 2A, Hg, Co, V, and Class 2B impurities such as Ni, T1, Se, Ag, Au, Pd, Ir, Os, Rh, Ru, and Pt. Total 17 elemental impurities were detected in Propafenone Hydrochloride and this method was employed for the regular sample analysis of 17 elemental impurities in Propafenone Hydrochloride for pharmaceutical use. The instrument conditions were set using RF power of 1550 W, auxiliary gas of 0.5 L/min, and nebulizer flow of 1.01 L/min nebulizer pump pressure was 0.10 rps, spray chamber temperature was 2°C, and mode used was He, He flow rate was 4.3 mL/min and the energy discrimination rate was 3.0 V. The technique is sensitive and may identify desirable elemental impurities within permissible regulatory limits when additional elements are present. The proposed ICP-MS approach has been found to be accurate, precise, linear, rugged, robust, and convenient for the quality control of the drug substance propafenone hydrochloride. The linearity results for each impurity were 0.9990. The methods were validated according to USP requirements and International Council for Harmonization ICH guidelines. The suggested approach is an excellent quality control tool for the concurrent quantitative assessment and detection of elemental contaminants at low levels in the drug substance propafenone hydrochloride.