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AIMS: Diabetic Retinopathy (DR) is a significant cause of vision loss in diabetic patients, making early detection and accurate severity classification essential for effective management and prevention. This study aims to develop an enhanced DR severity classification approach using advanced model architectures and transfer learning to improve diagnostic accuracy and support better patient care. METHODS: We propose a novel model, Xception Squeeze-and-Excitation Sparse Lightweight Multi-Level Attention U-Net (XceSE_SparseLwMLA-UNet), designed to classify DR severity using fundus images from the Messidor 1 and Messidor 2 datasets. The XceSE_SparseLwMLA-UNet integrates several advanced mechanisms: the Squeeze-and-Excitation (SE) mechanism for adaptive feature recalibration, the Sparse Lightweight Multi-Level Attention (SparseLwMLA) mechanism for effective contextual information integration, and transfer learning from the Xception architecture to enhance feature extraction capabilities. The SE mechanism refines channel-wise feature responses, while SparseLwMLA enhances the model's ability to identify complex DR patterns. Transfer learning utilizes pre-trained weights from Xception to improve generalization across DR severity levels. RESULTS: The proposed XceSE_SparseLwMLA-UNet model demonstrates superior performance in DR severity classification, achieving higher accuracy and improved multi-class F1 scores compared to existing models. The model's color-coded segmentation outputs offer interpretable visual representations, aiding medical professionals in assessing DR severity levels. CONCLUSIONS: The XceSE_SparseLwMLA-UNet model shows promise for advancing early DR diagnosis and management by enhancing classification accuracy and providing valuable visual insights. Its integration of advanced architectural features and transfer learning contributes to better patient care and improved visual health outcomes.
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Mars' water history is fundamental to understanding Earth-like planet evolution. Water escapes to space as atoms, and hydrogen atoms escape faster than deuterium giving an increase in the residual D/H ratio. The present ratio reflects the total water Mars has lost. Observations with the Mars Atmosphere and Volatile Evolution (MAVEN) and Hubble Space Telescope (HST) spacecraft provide atomic densities and escape rates for H and D. Large increases near perihelion observed each martian year are consistent with a strong upwelling of water vapor. Short-term changes require processes in addition to thermal escape, likely from atmospheric dynamics and superthermal atoms. Including escape from hot atoms, both H and D escape rapidly, and the escape fluxes are limited by resupply from the lower atmosphere. In this paradigm for the escape of water, the D/H ratio of the escaping atoms and the enhancement in water are determined by upwelling water vapor and atmospheric dynamics rather than by the specific details of atomic escape.
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Introduction: Rapid and accurate point-of-care (POC) tuberculosis (TB) diagnostics are a key priority to close the TB diagnostic gap of 3.1 million people without a diagnosis. Leveraging the recent surge in COVID-19 diagnostic innovation, we explored the potential adaptation of commercially available SARS-CoV-2 tests for TB diagnosis, aligning with World Health Organization (WHO) target product profiles (TPPs). Methods: A scoping review was conducted following PRISMA-ScR guidelines to systematically map commercially available POC molecular and antigen SARS-CoV-2 diagnostic tests potentially meeting the TPPs for TB diagnostic tests for peripheral settings. Data were gathered from PubMed/MEDLINE, bioRxiv, and medRxiv, along with publicly accessible in vitro diagnostic test databases, and developer websites, up to November 23, 2022. Data on developer and test attributes, operational characteristics, pricing, and clinical performance were charted using standardized data extraction forms. Each identified test was evaluated using a standardized scorecard. A narrative synthesis of the charted data is presented. Results: Our database search yielded 2,003 studies, from which 408 were considered eligible. Among these, we identified 58 commercialized diagnostic devices, including 17 near-POC antigen tests, one POC molecular test, 29 near-POC molecular tests, and 11 low-complexity molecular tests. We summarized the detailed characteristics, regulatory status, and clinical performance data of these tests. The LumiraDx (Roche, Switzerland) emerged as the highest- scoring near-POC antigen platform, while Visby (Visby, USA) was the highest-performing near-POC molecular platform. The Lucira Check-It (Pfizer, USA) was noted as the sole POC molecular test. The Idylla TM (Biocartis, Switzerland) was identified as the leading low- complexity molecular test. Discussion: We highlight a diverse landscape of commercially available diagnostic tests suitable for potential adaptation to TB POC testing. This work aims to bolster global TB initiatives by fostering stakeholder collaboration, leveraging COVID-19 diagnostic technologies for TB diagnosis, and uncovering new commercial avenues to tackle longstanding challenges in TB diagnosis.
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BACKGROUND: The COVID-19 pandemic posed numerous obstacles to psychosocial wellbeing for children. We conducted a longitudinal study to evaluate child mental health and social risks during the pandemic. METHODS: Participants were 172 caregivers of children aged 6-11 years old who attended well child visits within 6 months before pandemic onset at an urban safety net hospital in the US. Prepandemic data was extracted from the electronic medical record, and surveys were administered at three time points between August 2020 and July 2021. We measured mental health symptoms with the Pediatric Symptom Checklist-17, social risks (e.g., food and housing insecurity) with the THRIVE questionnaire, and school modality (in-person, hybrid, remote). RESULTS: Compared to pre-pandemic, children had significantly higher PSC-17 total scores (overall mental health symptoms) and THRIVE total scores (total burden of social risks) at all three mid-pandemic waves. Using longitudinal mixed models accounting for time, social risks, and school modality, both social risks (B = 0.37, SE = 0.14, p < 0.01) and school modality were significantly associated with PSC-17 scores (B = - 1.95, SE = 0.63, p < 0.01). Children attending in-person school had fewer mental health symptoms than those attending remote or hybrid school. CONCLUSION: Mental health symptoms and social risks remained significantly higher fifteen months after the onset of the COVID-19 pandemic compared to prepandemic. In-person attendance at school appeared protective against persistently elevated mental health symptoms.
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Irrigation is one of the steps that is very crucial in a high-quality endodontic treatment. Hence, irrigant with good substantivity is essential which must not only be effective for the dissolution of the organic tissues but also effectively eliminate bacterial contamination. The aim of the study was to investigate and compare the antimicrobial efficacy of gentamicin, amoxicillin, and metronidazole (GAM) antibiotic solution, chitosan and their combination (GAMC), and analyze their sustained release property. Mueller-Hinton agar medium was inoculated with E. faecalis. The medicaments were then poured at the center of the plate in the prepared wells and incubated at 37°C. Antibacterial property of each medicament was evaluated by measuring the diameter of the zone of inhibition at the end of 48 hours. The substantivity of GAM antibiotic solution and the GAMC was checked using an ultraviolet spectrophotometer. The GAMC demonstrated the strongest antimicrobial activity and good sustained-release properties. Distilled water showed no activity, and chlorhexidine acted as the positive control. Conclusion: The combination of gentamicin, amoxicillin, and metronidazole (GAM) solution with chitosan (GAMC) can be used as an alternative intracanal irrigant as it was found to be a potent antibacterial agent.
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Background and objectives Lupus vulgaris is a chronic, progressive, paucibacillary form of cutaneous tuberculosis that occurs in persons with moderate to high immunity. Due to its varied clinical presentation, it can masquerade as different dermatological conditions. This study describes the demographic patterns and varieties of clinical manifestations that can be possible in this curable illness. Methods This study was conducted over two years and included 19 patients with histopathologically confirmed lupus vulgaris in Odisha, India. Demographic data, clinical features, and response to treatment are presented. Results Thirteen cases (68.4%) were seen in adults and six (31.6%) in pediatric patients. The lower limbs were the more affected (n=10), followed by the upper limb (6), the face (2), and the chest (1). All but one patient had plaque-type lesions. On histopathology, all showed a tuberculoid granuloma with no demonstration of acid-fast bacilli with Ziehl-Neelsen staining. Conclusion In the present study, the incidence was mostly observed in the young and higher activity age groups (5-40 years). Plaque-type lesions were most commonly encountered. In histopathology, all the cases had tubercular granuloma-type lesions without any incidence of malignant transformations. All the patients responded well to conventional multi-drug anti-tubercular chemotherapeutic regimens.
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BACKGROUND: Lichen planus (LP) is a chronic inflammatory disorder caused by an autoimmune attack by cytotoxic T-cells. The clinical course is variable, with episodes of remission and exacerbation. A clinicopathological scoring system for cutaneous LP is not available for effectively assessing disease severity and monitoring treatment response. This study was designed with the aim of proposing an objective and reproducible scoring system, comprising histopathological features of active and chronic disease, and to correlate these scores with clinical morphology groups. METHODOLOGY: This is a retrospective study of 200 cases of cutaneous LP, which were categorized into five clinical groups (I-V) at the time of biopsy. The corresponding histopathological feature was assigned a score based on feature of active and chronic disease. Individual scores were summated to calculate a histopathological index (index [AI] and chronicity index [CI]). The comparison of indices between various clinical groups was performed by Mann-Whitney U test. RESULTS: The median AI was lowest (1) for post-inflammatory hyperpigmentation (clinical group I) and highest (7) for the bullous group (clinical group IV). The median CI (7) was highest for the scarring group (clinical group V). The difference between median AI of clinical group I (post-inflammatory hyperpigmentation) and rest of the groups (clinical groups II, III, IV, and V) was statistically significant (p value <0.05). CONCLUSION: We present this clinico-histopathological scoring system as a reliable and facile method of assessing the activity and severity of LP.
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Hiperpigmentação , Líquen Plano , Humanos , Estudos Retrospectivos , Líquen Plano/patologia , Cicatriz/patologia , Doença CrônicaRESUMO
Infection-associated hemophagocytosis is a diagnostic challenge. The varied presentation makes timely diagnosis difficult. We report two cases with unusual presentation of well-established secondary triggers for hemophagocytic lymphohistiocytosis.
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Background: Remarkable diversity of skin tones among Indians ranging from pale pinkish to dark brown appears to be an ideal choice for the assessment of skin pigment variation. Aim: The present study was designed to assess the variation observed in melanin and erythema indices among north Indians. Material and Methods: Skin reflectance data (n = 574) was collected from six diverse populations of north India using DermaSpectrometer (DSM II ColorMeter) followed by statistical analysis to investigate the impact of geographical location and gender on constitutive skin pigmentation. Results: The melanin index (MI) varied between 17.93 and 56.92 (Mean (M) = 35.80 ± 6.26) whereas the erythema index (EI) varied between 4.92 and 18.82 (M = 10.48 ± 2.68). MI and EI of females were found to be significantly lower than males (P < 0.001). Geographical location exhibited a significant association with MI and EI (P < 0.001). Furthermore, we have noted a positive correlation between MI and EI (P < 0.001). Conclusion: The study has refined our understanding of skin pigmentation variation among north Indians in terms of significant association with geographical location {MI: F (5,568) = 31.07, P < 0.001; EI: F (5,568) = 73.37, P < 0.001} and gender {MI: t (386) = -4.06, P < 0.001; EI: t (386) = -11.96, P < 0.001} and rendered opportunities for further studies.
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Purpose: Aging is one of the most important risk factors for a number of human diseases. Epigenetic alterations, including changes in DNA methylation patterns, have been reported to be one of the hallmarks of aging. Being a malleable process, the role of site-specific DNA methylation in aging is being extensively investigated; however, much less attention has been given to alterations in global DNA methylation with aging at the population level. The present study aims to explore overall and sex-specific variations in global DNA methylation patterns with age. Methods: A total of 1,127 adult individuals (792 females) aged 30-75 years belonging to Haryana, North India, were recruited. Socio-demographic data was collected using a pretested interview schedule. Global DNA methylation analysis, of peripheral blood leucocyte (PBL) DNA, was performed using the ELISA-based colorimetric technique. Results: Though the overall correlation analysis revealed a weak inverse trend between global DNA methylation and age, the adjusted regression model showed no significant association between global DNA methylation and age. In age-stratified analysis, global DNA methylation levels were found to be fairly stable until 60 years of age, followed by a decline in the above-60 age group. Further, no significant difference in DNA patterns methylation pattern was observed between males and females. Conclusion: Overall, the study suggests a lack of association between global DNA methylation and age, especially until 60 years of age, and a similar DNA methylation pattern between males and females with respect to age.
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Microscopic traits and ultrastructure of hair such as cross-sectional shape, pigmentation, curvature, and internal structure help determine the level of variations between and across human populations. Apart from cosmetics and anthropological applications, such as determining species, somatic origin (body area), and biogeographic ancestry, the evidential value of hair has increased with rapid progression in the area of forensic DNA phenotyping (FDP). Individuals differ in the features of their scalp hair (greying, shape, colour, balding, thickness, and density) and facial hair (eyebrow thickness, monobrow, and beard thickness) features. Scalp and facial hair characteristics are genetically controlled and lead to visible inter-individual variations within and among populations of various ethnic origins. Hence, these characteristics can be exploited and made more inclusive in FDP, thereby leading to more comprehensive, accurate, and robust prediction models for forensic purposes. The present article focuses on understanding the genetics of scalp and facial hair characteristics with the goal to develop a more inclusive approach to better understand hair biology by integrating hair microscopy with genetics for genotype-phenotype correlation research.
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Cabelo , Couro Cabeludo , Humanos , Fenótipo , DNA/genética , Genética Forense , Polimorfismo de Nucleotídeo ÚnicoRESUMO
Variability in the Martian upper atmosphere is strongly linked to the lower atmosphere and much of it can be attributed to vertical wave propagation. Atmospheric tides in particular are a well-known phenomenon in the Martian atmosphere that play a key role in the transport of energy as they propagate to higher altitudes. Previous theoretical predictions and observations suggest that tides producing wavenumber-2 and wavenumber-3 patterns are strongest in a fixed local time at high altitudes, however, the energy they carry and the region of deposition are not well characterized. Given the availability of atmospheric observations from several spacecraft at the same time, in this paper, the nature and behavior of tides are studied concurrently at several altitudes. Here, six intervals are identified focused at fixed low latitudes utilizing simultaneous observations of the middle and upper atmosphere from in situ and remote sensing instruments on different spacecraft. In the middle atmosphere, strong wavenumber-2 signatures are identified in the intervals north of the equator whereas, in the south, wavenumber-3 signatures are strongest. Wave signatures observed in the upper atmosphere seem to be dominated by a mix of wavenumbers-2 and -3. Seasonal variation is observed in the northern intervals, with very little interannual variability in all intervals considered. Estimates of energy based on dominant wavenumber amplitude suggest that most of the energy dissipates below â¼90 km. Furthermore, model sampled output captures the dominant wavenumbers observed in the middle atmosphere as well as the energy dissipation characteristics.
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COVID-19 is arguably the biggest health crisis the world has faced in the 21st century. Therefore, two of the polyherbal formulations, Infuza and Kulzam were assessed for the prevention of COVID-19 infection as a repurposed medication. Four hundred seven high-risk subjects were recruited in the present open-label randomized controlled clinical trial for eligibility. After assessment for eligibility, remaining 251 subjects were randomized to the test and control groups. Further, 52 high-risk subjects in Infuza, 51 in Kulzam, 51 in Infuza & Kulzam and 53 in control group completed the 14 days of intervention/assessment. The phenotyping of lymphocytes at baseline (0 day) and after 14 days of treatment was carried out by flow cytometry assays. A total of 15.09% high-risk subjects in control group turned positive as compared to only 7.69% in Infuza, 3.92% in Kulzam and 1.96% in Infuza & Kulzam groups. The rate of conversion to COVID-19 infection in Infuza & Kulzam group was minimal and statistically significant as compared to control group (p0.017). No significant changes in phenotype of lymphocytes (T, B, NK cells), absolute lymphocyte count and cytokine levels were found in study groups. However, there was a decreasing trend of hs-CRP level in high-risk subjects after intervention of polyherbal formulations for 14 days. The combination of Infuza and Kulzam may synergistically prevent COVID-19 infection in high-risk subjects of COVID-19.
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Tratamento Farmacológico da COVID-19 , COVID-19 , COVID-19/prevenção & controle , Humanos , SARS-CoV-2 , Resultado do TratamentoRESUMO
INTRODUCTION: Forensic DNA Phenotyping (FDP) has provided better understanding of various phenotypic features (e.g., height, skin colour, eye colour, structure and shape of scalp hair, baldness, facial features etc.) and associated genetic variations. The current study was designed to investigate the genetic variants and their potential contribution towards accurate phenotype prediction systems. Short Tandem Repeat (STR) based DNA typing method can be uninformative or with little potential to solve a crime in absence of suspect DNA profile in the database. Forensic DNA Phenotyping (FDP), prediction of externally visible characteristics (EVCs) from the crime scene DNA would certainly provide a new dimension to personal identification. The aim of this review paper is to highlight the significance and future prospects of FDP. RESULTS: A comprehensive literature review was conducted using PubMed and similar e-databases with keywords from two main components-phenotype and the associated genetic variants. To ensure a thorough literature review, searches were extended using the snowballing technique from reference lists. Key data extracted were type of study, sample characteristics (sample size, age, geographical location and ancestry), details of SNPs studied and prediction accuracies. CONCLUSION: Phenotyping tools based on genotyping and statistical analysis for the prediction of human pigmentation are propitious in solving cold cases. This indicates the inevitability of future studies for the identification of new genetic markers for accurate prediction of phenotype or EVCs via genome-wide association study (GWAS) in diverse global populations.
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Genética Forense , Estudo de Associação Genômica Ampla , Crime , DNA/análise , Genética Forense/métodos , Humanos , Fenótipo , Polimorfismo de Nucleotídeo ÚnicoRESUMO
For nearly 50 years, the vision of using single molecules in circuits has been seen as providing the ultimate miniaturization of electronic chips. An advanced example of such a molecular electronics chip is presented here, with the important distinction that the molecular circuit elements play the role of general-purpose single-molecule sensors. The device consists of a semiconductor chip with a scalable array architecture. Each array element contains a synthetic molecular wire assembled to span nanoelectrodes in a current monitoring circuit. A central conjugation site is used to attach a single probe molecule that defines the target of the sensor. The chip digitizes the resulting picoamp-scale current-versus-time readout from each sensor element of the array at a rate of 1,000 frames per second. This provides detailed electrical signatures of the single-molecule interactions between the probe and targets present in a solution-phase test sample. This platform is used to measure the interaction kinetics of single molecules, without the use of labels, in a massively parallel fashion. To demonstrate broad applicability, examples are shown for probe molecule binding, including DNA oligos, aptamers, antibodies, and antigens, and the activity of enzymes relevant to diagnostics and sequencing, including a CRISPR/Cas enzyme binding a target DNA, and a DNA polymerase enzyme incorporating nucleotides as it copies a DNA template. All of these applications are accomplished with high sensitivity and resolution, on a manufacturable, scalable, all-electronic semiconductor chip device, thereby bringing the power of modern chips to these diverse areas of biosensing.
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Técnicas Biossensoriais/instrumentação , Eletrônica/instrumentação , Ensaios Enzimáticos/instrumentação , Análise de Sequência com Séries de Oligonucleotídeos/instrumentação , DNA , Desenho de Equipamento/instrumentação , Cinética , Dispositivos Lab-On-A-Chip , Miniaturização/instrumentação , Nanotecnologia/instrumentação , SemicondutoresRESUMO
The programmable nature of sequence-specific targeting by CRISPR-Cas nucleases has revolutionized a wide range of genomic applications and is now emerging as a method for nucleic acid detection. We explore how the diversity of CRISPR systems and their fundamental mechanisms have given rise to a wave of new methods for target recognition and readout. These cross-disciplinary advances found at the intersection of CRISPR biology and engineering have led to the ability to rapidly generate solutions for emerging global challenges like the COVID-19 pandemic. We further discuss the advances and potential for CRISPR-based detection to have an impact across a continuum of diagnostic applications.
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COVID-19 , Sistemas CRISPR-Cas , COVID-19/diagnóstico , Sistemas CRISPR-Cas/genética , Endonucleases/metabolismo , Edição de Genes/métodos , Humanos , PandemiasRESUMO
BACKGROUND: There is concern about the effect of the COVID-19 pandemic on psychosocial functioning among school-age children, who have faced unusual stressors during this time. Our goal was to assess mental health symptoms and social risks during COVID-19, compared to before the pandemic, for urban, racial and ethnic minority school-age children, and investigate the relationship between mental health and social risks. METHODS: We conducted a cohort study from September 2019 until January 2021 of children age 5-11 years old recruited from an urban safety net hospital-based pediatric primary care practice. We measured emotional and behavioral symptoms (including attention, internalizing, and externalizing symptoms) before and during the pandemic with the Pediatric Symptom Checklist (PSC-17). We measured social risks (including food and housing insecurity) before and during the pandemic with the THRIVE screener. We measured additional mid-pandemic COVID-related stressors with items on school participation, screens/media use, illness exposure, and caregiver mental health. We compared pre- and mid-pandemic PSC-17 symptom scores across 4 domains (total, attention, internalizing, and externalizing) and used path analysis to examine the relationship between mental health and social risks pre- and mid-pandemic. RESULTS: Caregivers of 168 children (54% non-Hispanic Black, 29% Hispanic, and 22% non-English speaking) completed the study. Children had significantly higher levels of emotional and behavioral symptoms midpandemic- vs. pre-pandemic in all domains. Significantly more children had a positive PSC-17 total score (18% vs. 8%, p < 0.01) and internalizing (depression and anxiety) score (18% vs. 5%, p < 0.001) during the pandemic vs. before, indicating clinical concerns in these areas. Caregivers reported significantly more social risks during vs. before the pandemic (p < 0.001). Mental health symptoms significantly correlated with number of social risks before the pandemic, but not during the pandemic. Less school assignment completion, increased screen time, and caregiver depression were all significantly associated with worse mid-pandemic mental health in children. CONCLUSION: The COVID-19 pandemic has led to a dramatic increase in depression/anxiety problems and social risks among urban, racial and ethnic minority school-age children compared to before the pandemic. More research is needed to understand if these changes will persist.
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Acromioclavicular joint tuberculosis is an extremely rare presentation with only 16 cases reported so far and has a relatively high propensity to be misdiagnosed. India being a tuberculosis endemic region accounts for almost 27% of cases worldwide (global index of 2018 was 10 million). With a higher index of suspicion an earlier diagnosis can be made. We report two patients of AC joint tuberculosis, treated with multidrug chemotherapy resulting in a good functional outcome.