Class Ib Research Articles

HELIOS-expressing human CD8 T cells exhibit limited effector functions.

The transcription factor HELIOS is primarily known for its expression in CD4 regulatory T cells, both in humans and mice. In mice, HELIOS is found in exhausted CD8 T cells. However, information on human HELIOS+ CD8 T cells is limited and conflicting. In this study, we characterized by flow cytometry and transcriptomic analyses human HELIOS+ CD8 T cells. These T cells primarily consist of memory cells and constitute approximately 21% of blood CD8 T cells. In comparison with memory HELIOS- T-BEThigh CD8 T cells that displayed robust effector functions, the memory HELIOS+ T-BEThigh CD8 T cells produce lower amounts of IFN-γ and TNF-α and have a lower cytotoxic potential. We wondered if these cells participate in the immune response against viral antigens, but did not find HELIOS+ cells among CD8 T cells recognizing CMV peptides presented by HLA-A2 and HLA-B7. However, we found HELIOS+ CD8 T cells that recognize a CMV peptide presented by MHC class Ib molecule HLA-E. Additionally, a portion of HELIOS+ CD8 T cells is characterized by the expression of CD161, often used as a surface marker for identifying TC17 cells. These CD8 T cells express TH17/TC17-related genes encoding RORgt, RORa, PLZF, and CCL20. Our findings emphasize that HELIOS is expressed across various CD8 T cell populations, highlighting its significance beyond its role as a transcription factor for Treg or exhausted murine CD8 T cells. The significance of the connection between HELIOS and HLA-E restriction is yet to be understood.

An Ancestral Major Histocompatibility Complex Organization in Cartilaginous Fish: Reconstructing MHC Origin and Evolution.

Cartilaginous fish (sharks, rays, and chimeras) comprise the oldest living jawed vertebrates with a mammalian-like adaptive immune system based on immunoglobulins (Ig), T-cell receptors (TCRs), and the major histocompatibility complex (MHC). Here, we show that the cartilaginous fish "adaptive MHC" is highly regimented and compact, containing (i) a classical MHC class Ia (MHC-Ia) region containing antigen processing (antigen peptide transporters and immunoproteasome) and presenting (MHC-Ia) genes, (ii) an MHC class II (MHC-II) region (with alpha and beta genes) with linkage to beta-2-microglobulin (β2m) and bromodomain-containing 2, (iii) nonclassical MHC class Ib (MHC-Ib) regions with 450 million-year-old lineages, and (iv) a complement C4 associated with the MHC-Ia region. No MHC-Ib genes were found outside of the elasmobranch MHC. Our data suggest that both MHC-I and MHC-II genes arose after the second round of whole-genome duplication (2R) on a human chromosome (huchr) 6 precursor. Further analysis of MHC paralogous regions across early branching taxa from all jawed vertebrate lineages revealed that Ig/TCR genes likely arose on a precursor of the huchr9/12/14 MHC paralog. The β2m gene is linked to the Ig/TCR genes in some vertebrates suggesting that it was present at 1R, perhaps as the donor of C1 domain to the primordial MHC gene. In sum, extant cartilaginous fish exhibit a conserved and prototypical MHC genomic organization with features found in various vertebrates, reflecting the ancestral arrangement for the jawed vertebrates.

Heart failure: update of the ESC 2023 guidelines

The 2023 update of the European Society of Cardiology (ESC) guidelines recommends (classIA) the administration of sodium-glucose transporter 2inhibitors (SGLT2i) also for patients with heart failure with preserved ejection fraction (HFpEF) and mildly reduced EF (HFmrEF). Thus, SGLT2i are the only medication that should be given to all heart failure patients for improvement of prognosis independent of left ventricular EF. The rapid administration of the fantastic four drugs and their prompt titration after aheart failure decompensation is now included in the guidelines with a class IB recommendation. For patients with reduced EF (HFrEF) or HFmrEF and iron deficiency there is now a class IIa recommendation for intravenous administration of ferric carboxymaltose or ferric derisomaltose.

Evaluation of HLA-G 14 base-pair Insertion/ Deletion Polymorphism and Soluble HLA-G Level in Patients with Rheumatoid Arthritis in Mosul City: A Case-Control Study

Background: HLA-G antigens are unconventional “class Ib” entities that are found on human leukocytes; they are essential in immunomodulation and regulation of inflammatory processes. Studies on the effects of the gene variations of HLA-G on rheumatoid arthritis have inconsistent results. Objective: To estimate the potential relationship between soluble HLA-G and the rs66554220 14 base-pair insertion/deletion polymorphism of HLA-G with disease activity parameters of rheumatoid patients in Iraqi patients. Methods: Using a DNA extraction kit, the genomic DNA was retrieved from 190 rheumatoid cases and 190 control individuals. Using primers for the HLA-G gene, the polymerase chain reaction was utilized for the genotyping of HLA-G 14ֺ base-pair insertion/deletion variants. The levels of soluble HLA-G were assessed by means of an ELISA test. Results: The results did not show a link between polymorphic HLA-G 14 base-pair insertion/deletion alleles and the possibility of getting rheumatoid disease. Serum levels of soluble HLA-G were substantially lower than those of controls (median=1.548 vs. median=7.391 U/mL), respectively. sHLA-G has a statistically substantial adverse link with ESR (r= -0.245, p<0.05). Furthermore, there are statistically substantial differences between the DAS-28 activity score and the sHLA-G level. Conclusion: There is no link between the risk of developing RA and polymorphic HLA-G 14 base-pair insertion or deletion in Iraqi patients. However, sHLA-G might serve as a diagnostic predictor of disease activity.

Lamotrigine use and potential for adverse cardiac effects: A retrospective evaluation in a Veteran population

ObjectiveTo identify the impact of lamotrigine (LTG) on cardiac rhythm and conduction abnormalities for Veterans, an especially vulnerable population. BackgroundIn October 2020 the US Food and Drug Administration (FDA) added a new warning to the label of lamotrigine (Lamictal™) regarding its potential to cause cardiac rhythm and conduction abnormalities [1]. This warning came following in vitro data which suggested Class IB antiarrhythmic effects occurring at clinically achievable concentrations of lamotrigine [2]. However, it is unclear whether the in vitro findings will result in adverse clinical outcomes. Our objective was to assess for evidence for adverse clinical outcomes in a vulnerable population and examine for subtler signs of an association between lamotrigine and cardiac rhythm disturbances. MethodsA retrospective chart review was conducted using records between 10-01-2017 and 07-06-2021, identifying patients at the William S. Middleton Memorial Veterans Hospital who were prescribed lamotrigine. Data collected included: dates of lamotrigine initiation or discontinuation, lamotrigine dosing over the time of the prescription and maximum lamotrigine dose, any cardiac-related ICD-10-CM codes or a history of a cardiology appointment, EKGs with any abnormalities or changes, any concomitantly prescribed medications with known potential to cause cardiac abnormalities, any cardiac deaths. This retrospective chart review was approved by the University of Wisconsin-Madison Institutional Review Board. ResultsTwo hundred and thirty-three (189 male) patients with a lamotrigine prescription and 41.2 % (n = 96) of these patients had an EKG performed while prescribed lamotrigine. The average age of patients was 64.3 ± 13.0 (range 29 to 90) years and mean maximum lamotrigine daily dose was 250.8 ± 148.2 mg (range 25 to 800 mg). Nearly half (47.9 %, 46/96) of the patients were prescribed a concomitant sodium channel blocking medication in addition to lamotrigine. Eighty-four of the patients (87.5 %, 84/96) had a cardiac diagnosis, while 12 (12.5 %, 12/96) did not. A total of 12 deaths occurred within the review period, with two cardiac deaths from congestive heart failure. Four cases did not have information on cause of death. No LTG-associated cardiac adverse effects were noted as part of clinical care, though rash was noted in 5 cases. A total of 7 (7.3 %, 7/96) patients were found to have EKG abnormalities potentially related to lamotrigine, including 7.1 % (6/84) of those with a cardiac diagnosis and 8.3 % (1/12) of those without a cardiac diagnosis. ConclusionsWhile recent FDA warnings have suggested caution regarding cardiac complications associated with lamotrigine based on in vitro studies, the clinical implications are uncertain. Despite selecting a particularly vulnerable population, this retrospective chart review did not identify any deaths due to cardiac rhythm or conduction causes, nor demonstrate unambiguous cardiac complications related to lamotrigine. Even using permissive criteria (including any prolonged PR or QTc) to examine for subtle effects, only a low incidence (<10 %) of potential complications was found. Broader implications of this study are limited by the number of patients included and the retrospective nature of the study. Therefore, further studies are warranted to evaluate a link between cardiac complications and the use of lamotrigine, including the role of concomitant medications such as other sodium channel blocking agents and psychotropic medications.

Mexiletine: Antiarrhythmic mechanisms, emerging clinical applications and mortality.

Mexiletine, a class Ib antiarrhythmic drug, exhibits its major antiarrhythmic effect via inhibition of the fast and late Na+ currents in myocardial tissues that are dependent on the opening of Na+ channels for their excitation. Through a comprehensive examination of mexiletine's therapeutic benefits and potential risks, we aim to provide valuable insights that reinforce its role as a vital therapeutic option for patients with ventricular arrhythmias, long QT syndrome, and other heart rhythm disorders. This review will highlight the current understandings of the antiarrhythmic effects and rationales for recent off-label use and address the mortality and proarrhythmic effects of mexiletine utilizing published basic and clinical studies over the past five decades.

Lidocaine as an anti-arrhythmic drug: Are there any indications left?

Lidocaine is classified as a class Ib anti-arrhythmic that blocks voltage- and pH-dependent sodium channels. It exhibits well investigated anti-arrhythmic effects and has been the anti-arrhythmic of choice for the treatment of ventricular arrhythmias for several decades. Lidocaine binds primarily to inactivated sodium channels, decreases the action potential duration, and increases the refractory period. It increases the ventricular fibrillatory threshold and can interrupt life-threatening tachycardias caused by re-entrant mechanisms, especially in ischemic tissue. Its use was pushed into the background in the era of amiodarone and modern electric device therapy. Recently, lidocaine has come back into focus for the treatment of acute sustained ventricular tachyarrhythmias. In this brief overview, we review the clinical pharmacology including possible side effects, the historical course, possible indications, and current Guideline recommendations for the use of lidocaine.

Analysis of Providing Employee Performance Allowances at the Sambas Class IB Religious Court from an Islamic Economic Perspective

The purpose of this research is to determine and analyze the perceptions of Civil Servants at the Sambas Religious Court Class I B regarding the provision of performance allowances, the view of Islamic Economics towards the provision of performance allowances for Civil Servants at the Sambas Religious Court Class I B. This type of research uses field research. which uses qualitative descriptive data, namely research whose data is extracted through observations. The data sources in this research are Civil Servants of the Sambas Religious Court Class I B. The data collection methods used are interviews, documentation, reference searches. Data management and analysis collection techniques were carried out by conducting in-depth interviews with informants. The results of this research show that the provision of performance allowances to Civil Servants of the Sambas Class I B Religious Court has mostly experienced an increase in performance and level of discipline which can be seen from two aspects, namely attendance and monthly performance reports. And most of them are in accordance with Islamic views, this is because the allowances given are in accordance with employee performance. The implication of this research is that Civil Servants of the Sambas Religious Court Class I B should increase supervision of their employees so that they pay more attention to their duties and responsibilities so that the implementation of employees' main duties and functions can run well. Therefore, employees should use benefits as motivation for working.

Seizure and anatomical outcomes of repeat laser amygdalohippocampotomy for temporal lobe epilepsy: A single-institution case series

ObjectiveIn patients with treatment-refractory temporal lobe epilepsy (TLE), a single stereotactic laser interstitial thermotherapy (LITT) procedure is sometimes insufficient to ablate epileptogenic tissue, particularly the medial structures often implicated in TLE. In patients with seizure recurrence after initial ablation, the extent to which a second ablation may achieve improved seizure outcomes is uncertain. The objective of this study was to investigate the feasibility and potential efficacy of repeat LITT amygdalohippocampotomy as a worthwhile strategy for intractable temporal lobe epilepsy by quantifying changes to targeted mesial temporal lobe structures and seizure outcomes. MethodsPatients who underwent two LITT procedures for drug-resistant mesial TLE at our institution were included in the study. Lesion volumes for both procedures were calculated by comparing post-ablation intraoperative sequences to preoperative anatomy. Clinical outcomes after the initial procedure and repeat procedure were classified according to Engel scores. ResultsFive consecutive patients were included in this retrospective case series: 3 with right- and 2 with left-sided TLE. The median interval between LITT procedures was 294 days (range: 227–1918). After the first LITT, 3 patients experienced class III outcomes, 1 experienced a class IV, and 1 experienced a class IB outcome. All patients achieved increased seizure freedom after a second procedure, with class I outcomes (3 IA, 2 IB). ConclusionsRepeat LITT may be sufficient to achieve satisfactory seizure outcomes in some individuals who might otherwise be considered for more aggressive resection or palliative neuromodulation. A larger study to establish the potential value of repeat LITT amygdalohippocampotomy vs. other re-operation strategies for persistent, intractable temporal lobe epilepsy is worth pursuing.

The role of non-classical and chain-related human leukocyte antigen polymorphisms in laryngeal squamous cell carcinoma.

Laryngeal squamous cell carcinoma (LSCC) is the major pathological subtype of laryngeal cancer. It has been shown that alterations of the expression of non-classical human leukocyte antigens (HLA) and the chain-related MIC molecules by malignant cells can lead to escape from the immune system control and certain allele variants may participate in immune editing and therefore be associated with modulation of cancer risk. The aim of the present study was to investigate the role of non-classical HLA class Ib and chain-related MIC polymorphisms, determined at the allelic level by next-generation sequencing (NGS), in patients from the Bulgarian population, diagnosed with LSCC. In the present study DNA samples from 48 patients with LSCC were used. Data was compared to 63 healthy controls analysed in previous studies. HLA genotyping was performed by using the AlloSeq Tx17 early pooling protocol and the library preparation AlloSeq Tx17 kit (CareDx). Sequencing was performed on MiniSeq sequencing platform (Illumina) and HLA genotypes were assigned with the AlloSeq Assign analysis software v1.0.3 (CareDx) and the IPD-IMGT/HLA database 3.45.1.2. The HLA disease association tests revealed a statistically significant predisposing association of HLA-F*01:01:02 (Pc = 0.0103, OR = 24.0194) with LSCC, while HLA-F*01:01:01 (Pc = 8.21e-04, OR = 0.0485) has a possible protective association. Additionally we observed several haplotypes with statistically significant protective and predisposing associations. The strongest association was observed for F*01:01:01-H*01:01:01 (P = 0.0054, haplotype score=-2.7801). Our preliminary study suggests the involvement of HLA class Ib in cancer development and the possible role of the shown alleles as biomarkers of LSCC.

PENGARUH METODE SAS BERBANTUAN MEDIA GAMBAR TERHADAP KEMAMPUAN MEMBACA DAN MENULIS PERMULAAN SISWA KELAS I SD NEGERI 1 TAMBLANG

This study aims to analyze the effect of applying the synthetic structural analytic method (SAS) using image media on the reading and writing abilities of first grade students in elementary school using a quantitative approach. Quasi-experimental research design with a non-equivalent pretest posttest model. The study population was all students of class I SD Negeri 1 Tamblang, North Toraja Regency, totaling 59 students, divided into two study groups with each class IA, namely 29 students, while class IB consisted of 30 students. The sampling technique used the cluster random sampling technique and class IA as the experimental class while class IB as the control class. The data collection technique is using a performance test for writing and a preliminary reading test. based on the comparative analysis of the average reading ability at the beginning of the experimental class and the control class, the value of t = 7.495&gt; 1.69726 and sig. (2-tailed) = 0.001.69726 and sig. (2-tailed) = 0.00 &lt;0.05 this shows that the SAS method has a significant effect on the initial writing ability of class I students of SD Negeri 1 Tamblang

Investigation of cardiac arrhythmia events in patients treated with lamotrigine: FDA adverse event reporing system analysis.

In October 2020 and March 2021, the U.S. Food and Drug Administration (FDA) classified lamotrigine as a class IB antiarrhythmic, announcing an increased risk of heart rhythm problems. We sought to investigate the nature of the arrhythmia signal with lamotrigine use compared to anticonvulsants with sodium-blocking and non-sodium-blocking mechanisms. This retrospective pharmacovigilance case-non-case study used disproportionality analysis to detect signals of adverse reaction of interest reported with lamotrigine to the FDA Adverse Event Reporting System (FAERS) between 1998 and 2022. Our regression model adjusted for interacting concomitant medications. Sensitivity analyses included stratifying by indication and publication date. Overall, 2917 cases of heart rhythm problems with anticonvulsants were analyzed (1557 female [58.4%] and 1109 male [41.6%]). The mean age ± standard deviation (SD) was 43 ± 19, the groups did not differ significantly by age. Forty cases (7.91%) in the epileptic indication included more than one concomitant medication that influences cardiac conduction. The disproportionality signal for cardiac arrest did not differ for lamotrigine compared with other anticonvulsants, adjusted reporting odds ratio (adj.ROR, .88; 95% CI, .59-1.29) in the epileptic indication. A significantly lower reporting risk for bradyarrhythmia was identified with lamotrigine users in the epileptic population, (adj.ROR, .45; 95% confidence interval [CI], .29-.68). The psychiatric indication demonstrated a sixfold reporting risk for cardiac arrest compared to the epileptic indication. Concomitant medications that affect cardiac conduction, as well as reports on overdose and suicide attempts, were significant variables in psychiatric patients (ROR, 2.45; 95% CI, 2.21-2.71) and (ROR, 1.44; 95% CI, 1.34-1.55), respectively. Our results do not support a significant difference in the reporting risk for cardiac arrest, syncope, tachyarrhythmia, and bradyarrhythmia with lamotrigine in the epileptic indication. Signals of cardiac arrest in lamotrigine could be explained by confounding factors in the psychiatric indication, such as greater concomitant use of medications with cardiac adverse events, and greater reports on overdose and suicide attempts. We recommend that patients with polypharmacy undergo clinical and electrocardiographic monitoring. We illustrate the importance of examining signals for separate indications.

HLA-E-restricted SARS-CoV-2-specific T cells from convalescent COVID-19 patients suppress virus replication despite HLA class Ia down-regulation.

Pathogen-specific CD8+ T cell responses restricted by the nonpolymorphic nonclassical class Ib molecule human leukocyte antigen E (HLA-E) are rarely reported in viral infections. The natural HLA-E ligand is a signal peptide derived from classical class Ia HLA molecules that interact with the NKG2/CD94 receptors to regulate natural killer cell functions, but pathogen-derived peptides can also be presented by HLA-E. Here, we describe five peptides from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that elicited HLA-E-restricted CD8+ T cell responses in convalescent patients with coronavirus disease 2019. These T cell responses were identified in the blood at frequencies similar to those reported for classical HLA-Ia-restricted anti-SARS-CoV-2 CD8+ T cells. HLA-E peptide-specific CD8+ T cell clones, which expressed diverse T cell receptors, suppressed SARS-CoV-2 replication in Calu-3 human lung epithelial cells. SARS-CoV-2 infection markedly down-regulated classical HLA class I expression in Calu-3 cells and primary reconstituted human airway epithelial cells, whereas HLA-E expression was not affected, enabling T cell recognition. Thus, HLA-E-restricted T cells could contribute to the control of SARS-CoV-2 infection alongside classical T cells.

Implementasi Observasi Profiling Peserta Didik sebagai Persiapan Perencanaan Pembelajaran di Kelas IB SDN Gayamsari 02 Semarang

The aims of this study were (1) to map the learning styles of students in the learning design in class IB at SDN Gayamsari 02 Semarang (2) to design a learning design that is in accordance with the results of profiling observations of students in class IB at SD Negeri Gayamsari 02 Semarang. The research method used is descriptive qualitative. The population in this study were all grade 1 students at SD Negeri Gayamsari 02 Semarang, while the research sample was Class IB at SD Negeri Gayamsari 02 Semarang with a total of 26 students. There were 13 female students and 13 male students. The stages of this research are planning, implementation, and reflection. The observation results show that the designed learning has not been able to facilitate the diversity of the characteristics of students in the class. Preparation of the learning design begins with observing student profiling, followed by mapping learning styles, planning methods, models and approaches to be used in accordance with all student learning modalities. Learning design by making mapping. The use of the Teaching at The Right Level (TaRL) approach, the Problem Based Learning (PBL) learning model, and the Timeboard media in class IB SD Ngeri Gayamsari 02 Semarang. Reflection activities aim to identify and evaluate inappropriate learning designs.&#x0D; Keywords: Profiling, Learning Styles, Characteristics

THE EFFECT OF IMAGE MEDIA-ASSISTED SAS METHOD ON READING AND WRITING ABILITY IN BEGINNING OF THE FIRST GRADE STUDENTS OF SD NEGERI 1 SOPAI

The purpose of the research is to analyze The effect of the image media-assisted SAS method on reading and writing ability at the beginning of the first-grade students of SD Negeri 1 Sopai.This research uses a quantitative approach with a Quasi-experimental research design with a non-equivalent pretest-posttest model. The research population was all first-grade students of SD Negeri 1 Sopai, North Toraja Regency. The total population is 59 students, divided into two study groups, with each class IA being 29 students while class IB was 30 students. The sampling technique used random cluster sampling and class IA as the experimental class, while class IB was the control class. The data collection technique uses a performance test for writing and an initial reading test. Based on the comparative analysis of the average reading ability at the beginning of the experimental class and the control class, the value of t = 7.495&gt; 1.69726 and sig. (2-tailed) = 0.00&lt;0.05 states that the SAS method assisted by image media significantly affects the student's initial reading ability. For the students' initial writing ability, the t-value is 7.390&gt;1.69726 and sig. (2-tailed) = 0.00&lt;0.05, this shows that the SAS method significantly affects the writing ability of the first grader of SD Negeri 1 Sopai.

PENINGKATAN KREATIVITAS SISWA PADA MATERI BANGUN DATAR MENGGUNAKAN MODEL PROJECT BASED LEARNING (PJBL) DI KELAS 1 SDN PURWANTORO 1 KOTA MALANG

Creativity is a person's ability to find and create something new, new ways, new models, which are useful for himself and society. This research is one of the efforts of teachers or practitioners in the form of various activities carried out to improve funds or improve the quality of learning in the classroom through the application of project based learning learning methods which are expected to increase student creativity. The method used in CAR research (Classroom Action Research) uses the Kemmis and Mc Taggart Models, each cycle consisting of 4 stages in the PTK cycle, namely planning, acting, observing, and reflecting.The material used in this study is flat shape material which is applied to class 1B students at SDN Purwantoro 1 Malang. The research plan begins with observing learning problems that occur in class IB at SDN Purwantoro 1 Malang City. The results of the observational data analysis carried out during learning using the Project Based Learning learning method showed an increase in student creativity from cycle 1 and cycle 2. Where the highest percentage of using the PBL method on student creativity was 80% and was late for passing the KKM threshold that had been determined.

MR1 deficiency enhances IL-17-mediated allergic contact dermatitis.

Major histocompatibility complex (MHC) class Ib molecules present antigens to subsets of T cells primarily involved in host defense against pathogenic microbes and influence the development of immune-mediated diseases. The MHC class Ib molecule MHC-related protein 1 (MR1) functions as a platform to select MR1-restricted T cells, including mucosal-associated invariant T (MAIT) cells in the thymus, and presents ligands to them in the periphery. MAIT cells constitute an innate-like T-cell subset that recognizes microbial vitamin B2 metabolites and plays a defensive role against microbes. In this study, we investigated the function of MR1 in allergic contact dermatitis (ACD) by examining wild-type (WT) and MR1-deficient (MR1-/-) mice in which ACD was induced with 2,4-dinitrofluorobenzene (DNFB). MR1-/- mice exhibited exaggerated ACD lesions compared with WT mice. More neutrophils were recruited in the lesions in MR1-/- mice than in WT mice. WT mice contained fewer MAIT cells in their skin lesions following elicitation with DNFB, and MR1-/- mice lacking MAIT cells exhibited a significant increase in IL-17-producing αβ and γδ T cells in the skin. Collectively, MR1-/- mice displayed exacerbated ACD from an early phase with an enhanced type 3 immune response, although the precise mechanism of this enhancement remains elusive.

The Effect of Using Word Card Media on Beginning Reading Skills of Grade I Students of SD Inpres Barombong II, Tamalate District, Makassar City

This research uses a quantitative approach with the type of experimental research in the form of Quasi Experimental Design. This study aims to: (1) find out the description of the use of word cards in class 1 of SD Inpres Barombong II, Tamalate District, Makassar City, (2) find out how to describe initial reading skills using Word Card media for grade 1 SD Inpres Barombong II, Tamalate District. Makassar City, (3) found a significant effect of the use of word card media on the beginning reading skills of grade 1 Inpres Barombong II Elementary School, Tamalate District, Makassar City. The independent variable in this study was word card media while the dependent variable was reading skills. The population in this study were all grade 1 students of SD Inpres Barombong II, Tamalate District, Makassar City totaling 2 classes of 38 students, while the sample was class I A students totaling 21 students as an experimental class, then class IB as a control class totaling 17 students. The data collection technique used in this study was observation of the implementation of the learning process, reading tests were carried out twice, namely pretest and posttest and documentation in the form of learning tools and research documents. Research data analysis techniques using descriptive and inferential statistical analysis. Based on the results of the descriptive statistical analysis, it showed that the reading skills of the experimental class students differed from those of the control class. So it can be concluded that there is an effect of using word card media on students' initial reading skills. This is proven because there is a significant difference between the experimental class using word card media and the control class that does not use word card media.

Non-Classical HLA Class 1b and Hepatocellular Carcinoma.

A number of studies are underway to gain a better understanding of the role of immunity in the pathogenesis of hepatocellular carcinoma and to identify subgroups of individuals who may benefit the most from systemic therapy according to the etiology of their tumor. Human leukocyte antigens play a key role in antigen presentation to T cells. This is fundamental to the host's defense against pathogens and tumor cells. In addition, HLA-specific interactions with innate lymphoid cell receptors, such those present on natural killer cells and innate lymphoid cell type 2, have been shown to be important activators of immune function in the context of several liver diseases. More recent studies have highlighted the key role of members of the non-classical HLA-Ib and the transcript adjacent to the HLA-F locus, FAT10, in hepatocarcinoma. The present review analyzes the major contribution of these molecules to hepatic viral infection and hepatocellular prognosis. Particular attention has been paid to the association of natural killer and Vδ2 T-cell activation, mediated by specific HLA class Ib molecules, with risk assessment and novel treatment strategies to improve immunotherapy in HCC.

The Power of Trendy Flash Intro Builder 1.0 in the Teaching of Grammar

The purpose of the study was to look into the effectiveness of Trendy Flash Builder 1.0 software in teaching grammar. This study used a non-random sample of students from all demographics and a non-randomized pretest-posttest control group design. The subject of the study was implemented in the English department of UNIPA Blitar. The research subject for this study was a student from two classes, IA and IB, from which the treatment class was drawn at random. Class IB was the experimental group, receiving Trendy Flash Builder 1.0 software as a teaching medium, whereas Class IA was the control group, receiving no teaching media. As these groups differed on several parameters, ANCOVA was employed to try to reduce some of these disparities. As a result of data calculations, the research hypothesis was confirmed. It is possible to infer that Trendy Flash Builder 1.0 software as a teaching medium can have a significant impact on students' grammar achievement.