Composite Alginate Dialdehyde-Gelatin (ADA-GEL) Hydrogel Containing Short Ribbon-Shaped Fillers for Skeletal Muscle Tissue Biofabrication.

Skeletal muscle tissue can be severely damaged by disease or trauma beyond its ability to self-repair, necessitating the further development of biofabrication and tissue-engineering tools for reconstructive processes. Hence, in this study, a composite bioink of oxidized alginate (ADA) and gelatin (GEL) including cell-laden ribbon-shaped fillers is used for enhancing cell alignment and the formation of an anisotropic structure. Different plasma treatments combined with protein coatings were evaluated for the improvement of cell adhesion to poly(lactic-co-glycolic acid) (PLGA) ribbon surfaces. Oxygen plasma activation of 30 W for 5 min showed high immobilization of fibronectin as a protein coating on the PLGA ribbon surface, which resulted in enhanced cell adhesion and differentiation of muscle cells. Furthermore, the effect of various concentrations of CaCl2 solution, used for ionic cross-linking of ADA, on ADA-GEL physical and mechanical properties as well as encapsulated C2C12 cell viability and proliferation behavior was investigated. The pore area was measured via two approaches, cryofixation and lyophilization, which, in accordance with degradation tests and mechanical analysis, showed that 60 mM CaCl2 concentration is the optimum range for cross-linking of the formulation of ADA 2.5%w/v-GEL 3.75%w/v. These cross-linked hydrogels showed a compression modulus of 11.5 kPa (similar to the native skeletal muscle tissue), a high viability of C2C12 muscle cells (>80%), and a high proliferation rate during 7 days of culture. Rheological characterization of the ADA-GEL composite hydrogel containing short fillers (100 µm long) showed its suitability as a bioink with shear-thinning and flow behavior compared to ADA-GEL.

Diagnosis and Management of Tuberculous Pleural Effusion in a Patient With Chronic Obstructive Pulmonary Disease: A Case Report.

A 63-year-old man had been smoking bidis for 25 years and developed tubercular empyema, further complicated by pneumothorax and other pulmonary issues. Over a period of three weeks, the individual experienced a gradual onset of symptoms, including progressive shortness of breath, cough, fever, and chest pain. Radiographic examinations revealed significant left-sided pleural effusion with consolidation and evidence of pneumothorax. Other findings included anemia, hyponatremia, substantially increased lactate dehydrogenase, and adenosine deaminase (ADA), consistent with tubercular or chronic infection. The comprehensive treatment plan involved the administration of antibiotics, antitubercular drugs, draining of the pleural fluid, nebulized bronchodilators, corticosteroids, and broad-spectrum antibiotics. The patient exhibited a positive response, showing notable clinical improvement, which was closely monitored through sequential chest X-rays and ECGs. This would continue to highlight the vital need for early tuberculosis detection in patients with chronic obstructive pulmonary disease due to clinical overlap with other diseases. To diagnose and follow up on tuberculous pleural effusion cases, it was critical to integrate both clinical and radiographic findings with laboratory data. It emphasizes the necessity for a multidisciplinary approach to improve overall treatment outcomes.

Deficiency of Adenosine Deaminase 2

Adenosine deaminase 2 (ADA2) deficiency is an autosomal recessively inherited autoinflammatory disorder caused by loss-of-function mutations in the ADA2 gene. Although the pathogenesis involves the triggering of a proinflammatory cascade due to increased production of inflammatory cytokines such as tumor necrosis factor (TNF)-α and dysregulation of neutrophil extracellular trap formation resulting from an excess accumulation of extracellular adenosine, the pathogenetic mechanism still needs further clarification due to the broad clinical spectrum. In addition to the initially described vasculitis-related symptoms, hematological, immunological, and autoinflammatory symptoms are now well recognized. The diagnosis is made by demonstration of pathogenic variants of ADA2 with biallelic loss of function and identification of low plasma ADA2 catalytic activity. Currently, TNF-α inhibitors are the treatment of choice for controlling vasculitis manifestations and preventing strokes. However, in patients presenting with severe hematologic findings, TNF-α inhibitors are not the treatment of choice and hematopoietic stem cell transplantation has been shown to be successful in selected cases. Recombinant ADA2 protein and gene therapy are promising treatment modalities for the future. In conclusion, ADA2 deficiency has a broad phenotype and should be considered in the differential diagnosis of different clinical situations. In this review, we summarize the disease manifestations of ADA2 deficiency and available treatment options.

The SAGA acetyltransferase module is required for the maintenance of MAF and MYC oncogenic gene expression programs in multiple myeloma.

Despite recent advances in therapeutic treatments, multiple myeloma (MM) remains an incurable malignancy. Epigenetic factors contribute to the initiation, progression, relapse, and clonal heterogeneity in MM, but our knowledge on epigenetic mechanisms underlying MM development is far from complete. The SAGA complex serves as a coactivator in transcription and catalyzes acetylation and deubiquitylation. Analyses of data sets in the Cancer Dependency Map Project revealed that many SAGA components are selective dependencies in MM. To define SAGA-specific functions, we focused on ADA2B, the only subunit in the lysine acetyltransferase (KAT) module that specifically functions in SAGA. Integration of RNA sequencing (RNA-seq), assay for transposase-accessible chromatin with sequencing (ATAC-seq), and cleavage under targets and release using nuclease assay (CUT&RUN) results identified pathways directly regulated by ADA2B including MTORC1 signaling and oncogenic programs driven by MYC, E2F, and MM-specific MAF. We discovered that ADA2B is recruited to MAF and MYC gene targets, and that MAF shares a majority of its targets with MYC in MM cells. Furthermore, we found that the SANT domain of ADA2B is required for interaction with both GCN5 and PCAF acetyltransferases, incorporation into SAGA, and ADA2B protein stability. Our findings uncover previously unknown SAGA KAT module-dependent mechanisms controlling MM cell growth, revealing a vulnerability that might be exploited for future development of MM therapy.

Factors influencing accelerated aging in patients with type 2 diabetes mellitus and coronary heart disease.

Objective: To investigate the factors influencing accelerated aging in patients with type 2 diabetes mellitus (T2DM) and coronary heart disease (CHD). Methods: A total of 216 patients diagnosed with T2DM and CHD between August 2019 and August 2023 at Xuzhou Central Hospital were selected. Patients were divided into an aging group and a non-aging group, based on the positive or negative values of phenotypic age acceleration (PhenoAgeAccel). Logistic regression analysis was conducted. Variables that had a univariate analysis P< 0.05 were included in the multivariate analysis to identify factors influencing aging in patients with T2DM and CHD, and the area under the curve of the model was reported. Results: This study included 216 patients, with 89 in the accelerated aging group, and 127 in the non-accelerated aging group. The average age of patients was 70.40 (95% CI: 69.10-71.69) years, with 137 males (63.4%). Compared with the non-accelerated aging group, patients in the accelerated aging group were older, with a higher proportion of males, and a higher prevalence of hypertension, stable angina pectoris, and unstable angina pectoris. Multivariate Logistic regression analysis indicated that the absolute value of neutrophils (NEUT#), urea (UREA), adenosine deaminase (ADA), and the triglyceride-glucose index (TyG) were risk factors for accelerated aging, while cholinesterase (CHE) was a protective factor. For each unit increase in NEUT#, UREA, ADA, and TyG, the risk of aging increased by 64%, 48%, 10%, and 789%, respectively. The overall area under the receiver operating characteristic (ROC) curve of the model in the training set was 0.894, with a 95% confidence interval (CI) of 0.851-0.938. Conclusion: NEUT#, CHE, UREA, ADA, and TyG are predictors of accelerated aging in patients with T2DM and CHD, with the model showing favorable overall predictive performance.

The MYC-MAF-SAGA axis drives oncogenic gene expression in multiple myeloma.

The SAGA complex is an evolutionarily conserved histone acetyltransferase complex and transcription coactivator essential for development and disease. Dysregulation of SAGA is implicated in various human diseases, including cancer. In this issue of Genes & Development, Chen et al. (doi/10.1101/gad.351789.124) uncover a critical role for SAGA in multiple myeloma wherein SAGA's ADA2B component is required for the expression of mTORC1 pathway genes and targets of the MYC, E2F, and MAF (musculoaponeurotic fibrosarcoma) transcription factors. SAGA cooperates with MYC and MAF to sustain oncogenic gene expression programs vital for multiple myeloma survival and thus may serve as a therapeutic target for future cancer therapies.

A generic anti-drug antibody assay for monoclonal antibody therapeutics with broad dynamic range eliminates the need for titer evaluation in preclinical studies.

In preclinical protein therapeutic development studies, the emergence of anti-drug antibodies (ADA) can potentially impact drug pharmacokinetics and safety. While immunogenicity assessment is not mandatory in preclinical studies, banking samples can be valuable for interpreting unexpected pharmacological responses. Immunoassays that use generic reagents across different drug molecules can simplify ADA assessment and expedite sample evaluations. This work showcases the ability of the Gyrolab automated immunoassay platform to detect and quantify both drug-free and drug-bound (total) ADAs to monoclonal antibody (mAb) therapeutics in cynomolgus monkey preclinical studies. Compared to the previously reported total ADA ELISA, the Gyrolab assay exhibited a wider signal dynamic range and increased drug tolerance. Similar sensitivity, dynamic range and cut point factors were observed for four therapeutic mAbs of different isotypes using the Gyrolab assay. Here we present a comparison of ADA assays using bridging ELISA, total ADA ELISA and total ADA Gyrolab formats in a cynomolgus monkey study where the subjects were treated with a single dose of a mAb therapeutic. We demonstrate that the total ADA assays detected host ADA responses at earlier time points compared to the bridging ELISA. The Gyrolab assay has the best correlation between signal-to-noise (S/N) and titer over a wide ADA concentration range, highlighting the utility of Gyrolab in S/N reporting of ADA response to eliminate the need for secondary titer assays. Collectively, our results demonstrate that the generic ADA Gyrolab assay minimizes the necessity for extensive assay development and optimization for therapeutic mAbs, streamlining preclinical immunogenicity assessment to enable interpretation of pharmacological data.

Belimumab concentration measurements using a homologous anti-idiotype immunoassay.

Monitoring belimumab concentrations in patients can be a valuable tool for assessing treatment response and for personalizing drug doses. Various assay formats may be used to measure concentrations of therapeutic monoclonal antibodies. A particularly useful format involves the use of anti-idiotype monoclonal antibodies, selected to be highly specific to the antibody of interest. Here, we describe the development of a specific, high-affinity anti-idiotype antibody to belimumab, and the application of this antibody in a homologous sandwich ELISA to measure belimumab concentrations.

Low serum adrenic acid levels in infants and subsequent food-induced anaphylaxis.

Background: The dietary fat hypothesis links increases in allergic diseases to reduced consumption of n-3 polyunsaturated fatty acids from fish, for example, eicosapentaenoic acid, and increased intake of n-6 polyunsaturated fatty acids from vegetable oils, for example, arachidonic acid. Objective: Building upon the "fat hypothesis," we sought to investigate the association between 24 types of serum fatty acid levels in infants and the risk of subsequent food-induced anaphylaxis (FIA) by age 2 years as the primary outcome. Methods: This study was conducted as a prespecified supplemental analysis within the ABC randomized clinical trial. We measured levels of 24 fatty acids in residual serum samples collected from 268 infants at age 5 to 6 months using gas chromatography-mass spectrometry. Results: Among the 258 infants, 58 exhibited immediate-type food allergies, whereas 200 showed no food allergy. Of the 58 infants, 12 were diagnosed with FIA, whereas the remaining 46 had nonanaphylactic food allergy. Unexpectedly, among the 24 fatty acids, only adrenic acid, also known as docosatetraenoic acid, which is one of the n-6 polyunsaturated fatty acids, showed significantly lower levels in infants with FIA (median [interquartile range] (wt.%), 0.16 [0.14-0.17]), compared with those with no food allergy (0.19 [0.17-0.21]) (P = .0007). In contrast, adrenic acid levels in infants with nonanaphylactic food allergy were 0.19 [0.16-0.21] (wt.%), which did not differ significantly from those in infants with no food allergy (P = .69). Conclusions: This study generated a hypothesis suggesting that infants with low serum adrenic acid levels might be at greater risk of subsequent FIA. This unexpected result warrants further investigation.

Human ADA2 Deficiency: Ten Years Later.

PURPOSE OF REVIEW: In this review, an update is provided on the current knowledge and pending questions about human adenosine deaminase type 2 deficiency. Patients have vasculitis, immunodeficiency and some have bone marrow failure. Although the condition was described ten years ago, the pathophysiology is incompletely understood RECENT FINDINGS: Endothelial instability due to increased proinflammatory macrophage development is key to the pathophysiology. However, the physiological role of ADA2 is a topic of debate as it is hypothesized that ADA2 fulfils an intracellular role. Increasing our knowledge is urgently needed to design better treatments for the bone marrow failure. Indeed, TNFi treatment has been successful in treating DADA2, except for the bone marrow failure. Major advances have been made in our understanding of DADA2. More research is needed into the physiological role of ADA2.

Soluble CD26: From Suggested Biomarker for Cancer Diagnosis to Plausible Marker for Dynamic Monitoring of Immunotherapy.

Soluble CD26 (sCD26), a glycoprotein with dipeptidyl peptidase (DPP4) enzymatic activity, can contribute to early diagnosis of colorectal cancer and advanced adenomas and has been studied, including for prognostic purposes, across various other types of cancer and disease. The latest research in this field has confirmed that most, though not all, serum/plasma sCD26 is related to inflammation. The shedding and/or secretion of sCD26 from different immune cells are being investigated, and blood DPP4 activity levels do not correlate very strongly with protein titers. Some of the main substrates of this enzyme are key chemokines involved in immune cell migration, and both soluble and cell-surface CD26 can bind adenosine deaminase (ADA), an enzyme involved in the metabolism of immunosuppressor extracellular adenosine. Of note, there are T cells enriched in CD26 expression and, in mice tumor models, tumor infiltrating lymphocytes exhibited heightened percentages of CD26+ correlating with tumor regression. We employed sCD26 as a biomarker in the follow-up after curative resection of colorectal cancer for the early detection of tumor recurrence. Changes after treatment with different biological disease-modifying antirheumatic drugs, including Ig-CTLA4, were also observed in rheumatoid arthritis. Serum soluble CD26/DPP4 titer variation has recently been proposed as a potential prognostic biomarker after a phase I trial in cancer immunotherapy with a humanized anti-CD26 antibody. We propose that dynamic monitoring of sCD26/DPP4 changes, in addition to well-known inflammatory biomarkers such as CRP already in use as informative for immune checkpoint immunotherapy, may indicate resistance or response during the successive steps of the treatment. As tumor cells expressing CD26 can also produce sCD26, the possibility of sorting immune- from non-immune-system-originated sCD26 is discussed.

Knowledge and prescribing behaviour of Flemish general practitioners regarding novel glucose-lowering medications: Online cross-sectional survey.

AIMS: To determine the knowledge and prescribing behaviour regarding new type 2 diabetes medication in general practice. Physicians in Belgium are bound by the prescription criteria which do not always correspond to the international guidelines. DESIGN & METHOD: A mixed methods study with an online questionnaire was conducted in Flanders to collect data on demographic characteristics, theoretical knowledge, and prescribing behaviour, using ten theoretical questions and six clinical cases, based on the American Diabetes Association/European Association for the Study of Diabetes (ADA/EASD) guidelines and the Belgian reimbursement criteria. RESULTS: 201 GPs and GPs in training were included in this study with a median age of 30 years and 68 % female participants. On the knowledge questionnaire, the mean test result was 7.15/15 (= 48 %) with a median of 8. Further analysis showed that 90 % of the respondents correctly recommended a sodium-glucose cotransporter 2 (sglt2) inhibitor when the clinical case showed a comorbidity of heart failure, whereas only 42 % suggested correctly a glucagon-like peptide 1 (GLP-1) agonist if presence of cardiovascular disease. Subgroup analysis showed no statistically significant demographic differences in obtained test results. Regarding prescription behaviour, 23 % of the respondents would prescribe medication that did not match the reimbursement criteria in at least one of the 6 proposed clinical cases. CONCLUSION: This study highlights the need for enhanced knowledge and updated prescribing practices among Flemish GPs and Trainee GPs to effectively manage patients with T2DM.

Characterization of anti-drug antibody responses to the T-cell engaging bispecific antibody cibisatamab to understand the impact on exposure.

An appropriately designed pharmacokinetic (PK) assay that is sensitive for anti-drug antibody (ADA) impact on relevant exposure is an alternative strategy to understand the neutralizing potential of ADAs. However, guidance on how to develop such PK assays and how to confirm the functional ADA impact on exposure is missing. Here, the PK assay of a T-cell-engaging bispecific antibody, cibisatamab, was developed based on its mechanism of action (MoA). Using critical monoclonal anti-idiotypic (anti-ID) antibody positive controls as ADA surrogates, the impact on exposure was evaluated pre-clinically. In a phase I clinical trial (NCT02324257), initial data suggest that the combination of ADA and PK assays for correlation of the ADA response with cibisatamab exposure. To understand the neutralizing potential of patient-derived ADAs on drug activity, advanced ADA characterization has been performed. Structural binding analysis of ADAs to antibody domains of the drug and its impact on targeting were assessed. For this purpose, relevant patient ADA binding features were identified and compared with the specific monoclonal anti-ID antibody-positive controls. Comparable results of target binding inhibition and similar impacts on exposure suggest that the observed reduction of Cmax and Ctrough levels in patients is caused by the neutralizing potential of ADAs and allows a correlation between ADA response and loss of exposure. Therefore, the described study provides important functional aspects for the development of an appropriately designed PK assay for bispecific antibodies as an alternative option towards understanding the neutralizing ADA impact on exposure.

Dual release of daptomycin and BMP-2 from a composite of ß-TCP ceramic and ADA gelatin.

BACKGROUND: Antibiotic-containing carrier systems are one option that offers the advantage of releasing active ingredients over a longer period of time. In vitro sustained drug release from a carrier system consisting of microporous ß-TCP ceramic and alginate has been reported in previous works. Alginate dialdehyde (ADA) gelatin gel showed both better mechanical properties when loaded into a ß-TCP ceramic and higher biodegradability than pure alginate. METHODS: Dual release of daptomycin and BMP-2 was measured on days 1, 2, 3, 6, 9, 14, 21, and 28 by HPLC and ELISA. After release, the microbial efficacy of the daptomycin was verified and the biocompatibility of the composite was tested in cell culture. RESULTS: Daptomycin and the model compound FITC protein A (n = 30) were released from the composite over 28 days. A Daptomycin release above the minimum inhibitory concentration (MIC) by day 9 and a burst release of 71.7 ± 5.9% were observed in the loaded ceramics. Low concentrations of BMP-2 were released from the loaded ceramics over 28 days.

Gibberellin Signaling through RGA Suppresses GCN5 Effects on Arabidopsis Developmental Stages.

Histone acetyltransferases (HATs) modify the amino-terminal tails of the core histone proteins via acetylation, regulating chromatin structure and transcription. GENERAL CONTROL NON-DEREPRESSIBLE 5 (GCN5) is a HAT that specifically acetylates H3K14 residues. GCN5 has been associated with cell division and differentiation, meristem function, root, stem, foliar, and floral development, and plant environmental response. The flowers of gcn5 plants display a reduced stamen length and exhibit male sterility relative to the wild-type plants. We show that these effects may arise from gibberellin (GA)-signaling defects. The signaling pathway of bioactive GAs depends on the proteolysis of their repressors, DELLA proteins. The repressor GA (RGA) DELLA protein represses plant growth, inflorescence, and flower and seed development. Our molecular data indicate that GCN5 is required for the activation and H3K14 acetylation of genes involved in the late stages of GA biosynthesis and catabolism. We studied the genetic interaction of the RGA and GCN5; the RGA can partially suppress GCN5 action during the whole plant life cycle. The reduced elongation of the stamen filament of gcn5-6 mutants is reversed in the rga-t2;gcn5-6 double mutants. RGAs suppress the GCN5 effect on the gene expression and histone acetylation of GA catabolism and GA signaling. Interestingly, the RGA and RGL2 do not suppress ADA2b function, suggesting that ADA2b acts downstream of GA signaling and is distinct from GCN5 activity. In conclusion, we propose that the action of GCN5 on stamen elongation is partially mediated by RGA and GA signaling.

Chickpea production restored through upscaling crowdsourcing winner varieties and planting date adjustments in the Ada'a district, East Shoa zone, Ethiopia.

Chickpea is an important cash crop for Ada'a farmers as it does for farmers in Ethiopia and elsewhere in the world. Its production, however, has been dwindling due to biotic and abiotic stresses. According to participant farmers from Ada'a district, the production of chickpea in some Kebeles of Ada'a such as Gubasaye has been abandoned because of root rot and foliar diseases such as fusarium wilt. This paper presents the evaluation of upscaled varieties' performance assessed by metric data as well as through beneficiary farmers' self-assessment data. Recognizant to the problem, five varieties of chickpea tested in the Goro district of the Southwest Shoa zone, were introduced as part of the upscaling of crowdsourcing winner crop varieties in Ethiopia. Crowdsourcing is an approach of outsourcing variety evaluation, selection, and dissemination to volunteer crowds of farmers. The introduction of the winner varieties and adjustment of the planting time was found effective in the Ada'a district. Higher grain yield was obtained from the upscaled winner varieties in the range of 2.4-2.53 t/ha, with slight variations over varieties. Habru variety showed slightly higher performance than the others. Survey participant farmers have reported an increase in GY due to growing the winner varieties compared with varieties they used to grow before and gained higher annual income due to higher productivity, market demand of the upscaled varieties, and premium market price with 6-25 Ethiopian birr (ETB) per kilogram of sold grain of these varieties. High productivity is attributed to the genetic potential of the varieties, their response to farm management, and better adaptation to the local growing conditions. Participant farmers perceived that their livelihood has been improving because of the adoption of the upscaled varieties' productivity and market demand. The annual income of participant farmers is estimated to be 2500 to 181,000 ETB for growing the winner varieties. The results indicate that upscaling pre-tested chickpea varieties and delaying their planting time to early September are effective mechanisms for reducing yield loss to fusarium wilt and root rot diseases. It can be inferred that using the crowdsourcing approach for variety evaluation and selection for upscaling is a robust approach to improve the adoption and dissemination of improved agricultural technologies.

ADA/CD26 axis increases intra-tumor PD-1+CD28+CD8+ T-cell fitness and affects NSCLC prognosis and response to ICB.

Improving cancer immunotherapy efficacy hinges on identifying key T-cell populations critical for tumor control and response to Immune Checkpoint Blockade (ICB). We have recently reported that while the co-expression of PD-1 and CD28 is associated with impaired functionality in peripheral blood, it significantly enhances T-cell fitness in the tumor site of non-small cell lung cancer (NSCLC) patients. To uncover the underlying mechanisms, we explored the role of CD26, a key player in T-cell activation through its interaction with adenosine deaminase (ADA), a crucial intra/extracellular enzyme able to neutralize local adenosine (ADO). We found that an autocrine ADA/CD26 axis enhances CD8+PD-1+CD28+ T-cell function, particularly within an immunosuppressive environment marked by CD39 expression. Then, we interrogated the TCGA and OAK datasets to gain insight into the prognostic/predictive potential of our findings. We identified a signature predicting overall survival (OS) in LUAD patients and response to atezolizumab in advanced LUAD cases. These findings suggest promising avenues for therapeutic intervention targeting the ADA/CD26 axis.

A novel approach for melanoma detection utilizing GAN synthesis and vision transformer.

BACKGROUND AND OBJECTIVE: Melanoma, a malignant form of skin cancer, is a critical health concern worldwide. Early and accurate detection plays a pivotal role in improving patient's conditions. Current diagnosis of skin cancer largely relies on visual inspections such as dermoscopy examinations, clinical screening and histopathological examinations. However, these approaches are characterized by low efficiency, high costs, and a lack of guaranteed accuracy. Consequently, deep learning based techniques have emerged in the field of melanoma detection, successfully aiding in improving the accuracy of diagnosis. However, the high similarity between benign and malignant melanomas, combined with the class imbalance issue in skin lesion datasets, present a significant challenge in further improving the diagnosis accuracy. We propose a two-stage framework for melanoma detection to address these issues. METHODS: In the first stage, we use Style Generative Adversarial Networks with Adaptive discriminator augmentation synthesis to generate realistic and diverse melanoma images, which are then combined with the original dataset to create an augmented dataset. In the second stage, we utilize a vision Transformer of BatchFormer to extract features and detect melanoma or non-melanoma skin lesions on the augmented dataset obtained in the previous step, specifically, we employed a dual-branch training strategy in this process. RESULTS: Our experimental results on the ISIC2020 dataset demonstrate the effectiveness of the proposed approach, showing a significant improvement in melanoma detection. The method achieved an accuracy of 98.43%, an AUC value of 98.63%, and an F1 value of 99.01%, surpassing some existing methods. CONCLUSION: The method is feasible, efficient, and achieves early melanoma screening. It significantly enhances detection accuracy and can assist physicians in diagnosis to a great extent.

The Americans with Disabilities Act and Medication Assisted Treatment in Correctional Settings.

Studies estimate that least 65% of people incarcerated in the United States have Substance Use Disorder (SUD). Medication Assisted Treatment (MAT) is a proven effective treatment for Opioid Use Disorder (OUD). MAT reduces the number of people who die each year from OUD by fifty percent and ninety percent of individuals in recovery maintain sobriety after two years. Title II of the Americans with Disabilities Act (ADA) covers the programs and services provided by state and local governments including correctional facilities. Under the ADA, correctional facilities must make reasonable modification to policies and practice to allow inmates in recovery to have access to MAT. In this article, we discuss how the ADA applies to correctional facilities and the impact that MAT has for people who have OUD.