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ChatGPT is a popular information system (over 1 billion visits in August 2023) that can generate natural language responses to user queries. It is important to study the quality and equity of its responses on health-related topics, such as vaccination, as they may influence public health decision-making. We use the Vaccine Hesitancy Scale (VHS) proposed by Shapiro et al.1 to measure the hesitancy of ChatGPT responses in English, Spanish, and French. We find that: (a) ChatGPT responses indicate less hesitancy than those reported for human respondents in past literature; (b) ChatGPT responses vary significantly across languages, with English responses being the most hesitant on average and Spanish being the least; (c) ChatGPT responses are largely consistent across different model parameters but show some variations across the scale factors (vaccine competency, risk). Results have implications for researchers interested in evaluating and improving the quality and equity of health-related web information.
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Aims: To determine demographic details, clinical profile, and underlying causes of limbal stem cell deficiency. Settings and Design: Descriptive cross-sectional study. Methods and Material: Patients visiting tertiary referral hospitals between January 2019 and December 2022 who satisfy the criteria for labeling limbal stem cell deficiency (LSCD) were enrolled. Parameters such as age, gender, region, duration, aetiology, and clinical features were noted. Descriptive statistics was applied. The student t-test was used. Results: A total of 731 eyes of 489 patients with LSCD were included in our study, with age ranging from 5 to 85 years (35.0 ± 19.4 years). The most common presenting complaints were a decrease in vision 473 (96.7%), most of them 342 (69.7%) are having history of gradual progression (>3 months), and 245 (50.1%) have bilateral involvement of eyes. Average corneal clarity was found to be grade 1.6 ± 1.2 and average corneal superficial neovascularization was found to be 7.9 ± 4.3 quadrants. Clinically, we found LSCD of about up to 90° in 57 eyes, 90 to 180° in 71 eyes, 215 eyes with 180 to 270°, and the rest of 388 eyes were having more than 270° of LSCD involvement. Out of 489 patients, 142 (29.0%) patients were of chemical injury, 125 (25.6%) patients were of Steven Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN), followed by 61 (12.5%) patients of vernal keratoconjunctivitis (VKC). Conclusions: The majority of patients were young males presented with more than 270° LSCD and vision <2/60. In our study, chemical injury was most common in unilateral LSCD and SJS/TEN in bilateral LSCD.
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The security of web applications in an enterprise is of paramount importance. To strengthen the security of applications, the identification and mitigation of vulnerabilities through appropriate countermeasures becomes imperative. The Open Web Application Security Project (OWASP) Top 10 API Security Risks, 2023 Edition, indicates the prominent vulnerabilities of API security risks. Broken authentication, however, is placed in second position with level-3 exploitability, level-2 prevalence, level-3 detectability, and level-3 technical impact. To mitigate this vulnerability, many mitigation strategies have been proposed by using the cryptographic primitives wherein two techniques, namely hashing and PUF, are used. Some of the proposals have integrated the concepts of hashing and PUF. However, the unnecessarily lengthy and complex mathematics used in these proposals makes them unsuitable for current API-based application scenarios. Therefore, in this paper, the authors propose a privacy-preserving authentication protocol that incorporates the capability of both mechanisms in an easy and low-complexity manner. In addition to overcoming existing limitations, the proposed protocol is tested to provide more security properties over existing schemes. Analysis of their performance has demonstrated that the proposed solutions are secure, efficient, practical, and effective for API-based web applications in an enterprise environment.
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Hair and nails are human biomarkers capable of providing a continuous assessment of the concentrations of elements inside the human body to indicate the nutritional status, metabolic changes, and the pathogenesis of various human diseases. Laser-induced breakdown spectroscopy (LIBS) and X-ray fluorescence (XRF) spectrometry are robust and multi-element analytical techniques able to analyze biological samples of various kinds for disease diagnosis. The primary objective of this review article is to focus on the major developments and advances in LIBS and XRF for the elemental analysis of hair and nails over the last 10-year period. The developments in the qualitative and quantitative analyses of human hair and nail samples are discussed in detail, with special emphasis on the key aspects of elemental imaging and distribution of essential and non-essential elements within the hair and nail tissue samples. Microchemical imaging applications by LIBS and XRF (including micro-XRF and scanning electron microscopy, SEM) are also presented for healthy as well as diseased tissue hair and nail samples in the context of disease diagnosis. In addition, main challenges, prospects, and complementarities of LIBS and XRF toward analyzing human hair and nails for disease diagnosis are also thoroughly discussed here.
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The success of assisted reproduction relies on functional competence of frozen-thawed semen. Heat stress affects protein folding leading to aggregation of mis-folded proteins. Hence, a total of 384 (32 ejaculates/bull/season) ejaculates from six matured Gir bulls were used to evaluate physico-morphological parameters, the expression of HSPs (70 and 90) and fertility of frozen-thawed semen. The mean percent individual motility, viability and membrane integrity were significantly (p < 0.01) higher in winter compared to summer. Out of 1200 Gir cows inseminated, 626 confirmed pregnant and the mean conception rate of winter (55.04 ± 0.35) was significantly (p < 0.001) higher than summer (49.33 ± 0.32). A significant (p < 0.01) difference in concentration of HSP70 (ng/mg of protein) but not HSP90was observed between the two seasons. The HSP70 expression in pre-freeze semen of Gir bulls had significant positive correlation with motility (p < 0.01, r = 0.463), viability (p < 0.01, r = 0.565), acrosome integrity (p < 0.05, r = 0.330) and conception rate (p < 0.01, r = 0.431). In conclusion, the season influences physico-morphological parameters and expression of HSP70 but not HSP90 in Gir bull semen. The HSP70 expression is positively correlated with motility, viability, acrosome integrity and fertility of semen. The semen expression of HSP70 may be utilized as biomarker for thermo-tolerance, semen quality and fertilizing capacity of Gir bull semen.
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Preservación de Semen , Semen , Embarazo , Femenino , Bovinos , Animales , Masculino , Análisis de Semen/veterinaria , Estaciones del Año , Espermatozoides , Proteínas de Choque Térmico , Preservación de Semen/veterinaria , Proteínas HSP70 de Choque Térmico/genética , Motilidad Espermática , Criopreservación/veterinariaRESUMEN
BACKGROUND: Approximately 1 in 5 American adults experience mental illness every year. Thus, mobile phone-based mental health prediction apps that use phone data and artificial intelligence techniques for mental health assessment have become increasingly important and are being rapidly developed. At the same time, multiple artificial intelligence-related technologies (eg, face recognition and search results) have recently been reported to be biased regarding age, gender, and race. This study moves this discussion to a new domain: phone-based mental health assessment algorithms. It is important to ensure that such algorithms do not contribute to gender disparities through biased predictions across gender groups. OBJECTIVE: This research aimed to analyze the susceptibility of multiple commonly used machine learning approaches for gender bias in mobile mental health assessment and explore the use of an algorithmic disparate impact remover (DIR) approach to reduce bias levels while maintaining high accuracy. METHODS: First, we performed preprocessing and model training using the data set (N=55) obtained from a previous study. Accuracy levels and differences in accuracy across genders were computed using 5 different machine learning models. We selected the random forest model, which yielded the highest accuracy, for a more detailed audit and computed multiple metrics that are commonly used for fairness in the machine learning literature. Finally, we applied the DIR approach to reduce bias in the mental health assessment algorithm. RESULTS: The highest observed accuracy for the mental health assessment was 78.57%. Although this accuracy level raises optimism, the audit based on gender revealed that the performance of the algorithm was statistically significantly different between the male and female groups (eg, difference in accuracy across genders was 15.85%; P<.001). Similar trends were obtained for other fairness metrics. This disparity in performance was found to reduce significantly after the application of the DIR approach by adapting the data used for modeling (eg, the difference in accuracy across genders was 1.66%, and the reduction is statistically significant with P<.001). CONCLUSIONS: This study grounds the need for algorithmic auditing in phone-based mental health assessment algorithms and the use of gender as a protected attribute to study fairness in such settings. Such audits and remedial steps are the building blocks for the widespread adoption of fair and accurate mental health assessment algorithms in the future.
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Laser-induced breakdown spectroscopy (LIBS) has been widely applied to material classification in various fields, and partial least squares-discriminant analysis (PLS-DA) is one of the frequently used classical multivariate statistics to construct classification models based on the LIBS spectra. However, classification accuracy of the PLS-DA model is sensitive to the number of classes and their similarities. Considering this characteristic of PLS-DA, we suggest a two-step PLS-DA modeling approach to improve the classification accuracy. This strategy was demonstrated for a six-class problem in which six commercial edible sea salts produced in Japan, South Korea, and France are classified using their LIBS spectra. At the first step, test spectra were sorted into four classes and one extended class, composed of the two other most confusing classes, and then the test spectra in the extended class were further classified into each of the two constituent classes which were modeled separately from the other four classes. This two-step classification has been found to remarkably improve the PLS-DA classification accuracy by maximizing the difference between the confusing classes in the second-step modeling.
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Rayos Láser , Sales (Química) , Análisis Discriminante , Análisis de los Mínimos Cuadrados , Análisis Espectral/métodosRESUMEN
Understanding the mode of gene action that controls seed yield and Sclerotinia stem rot resistance in Indian mustard is critical for boosting yield potential. In a line × tester mating design, ten susceptible lines and four resistant testers were used to conduct genetic analysis. The significance of general combining ability (GCA) and specific combining ability (SCA) variances revealed that both additive and non-additive gene actions were involved in the inheritance of Sclerotinia stem rot resistance and yield attributing traits. In addition to 1000-seed weight and number of primary and secondary branches/plant, the genotypes RH 1569 (line) and DRMR 2035 (tester) appeared to be the strongest general combiners for Sclerotinia stem rot resistance. RH 1657 × EC 597317 was the only cross among several that demonstrated a significant desired SCA value for Sclerotinia rot resistance. Regarding SCA effects for yield and component traits, the cross RH 1658 × EC 597328 performed best, with a non-significant but acceptable negative SCA effect for resistance. DRMR 2035, RH 1222-28, RH 1569, RH 1599-41, RH 1657, RH 1658, and EC 597328 are promising genotypes to use as parents in future heterosis breeding and for obtaining populations with high yield potential and greater resistance to Sclerotinia stem rot disease in Indian mustard, based on GCA effects of parents, per se performance, and SCA effects of hybrids. Days to 50% flowering, number of primary branches/plant, main shoot length, and 1000-seed weight all had a high genotypic coefficient of variability (GCV), broad-sense heritability (h2bs), and genetic advance as percent of the mean (GAM) values, as well as significant and desirable correlations and direct effects on seed yield. As a result, these traits have been recognized as the most critical selection criterion for Indian mustard breeding programs.
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As the impact of the COVID-19 pandemic grew in 2020, uncertainty surrounding its origins and nature led to widespread conspiracy-related theories (CRT). Use of technological platforms enabled the rapid and exponential dissemination of COVID-19 CRT. This study applies social contagion theory to examine how Google Autocomplete (GA) propagates and perpetuates these CRT. An in-house software program, Autocomplete Search Logging Tool (ASLT) captured a snapshot of GA COVID-19 related searches early in the pandemic (from March to May 2020) across 76 randomly-selected countries to gain insight into search behaviors around the world. Analysis identified 15 keywords relating to COVID-19 CRT predictions and demonstrate how searches across different countries received varying degrees of GA predictions. When grouped with similar keywords, two major categories were identified "Man-Made Biological Weapon" (42%, n = 2,111), and "Questioning Reality/Severity of COVID-19" (44%, n = 2,224). This investigation is also among the first to apply social contagion theory to autocomplete applications and can be used in future research to explain and perhaps mitigate the spread of CRT.
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Sclerotinia stem rot is one of the utmost important disease of mustard, causing considerable losses in seed yield and oil quality. The study of the genetic and proteomic basis of resistance to this disease is imperative for its effective utilization in developing resistant cultivars. Therefore, the genetic pattern of Sclerotinia stem rot resistance in Indian mustard was studied using six generations (P1, P2, F1, F2, BC1P1, and BC1P2) developed from the crossing of one resistant (RH 1222-28) and two susceptible (EC 766300 and EC 766123) genotypes. Genetic analysis revealed that resistance was governed by duplicate epistasis. Comparative proteome analysis of resistant and susceptible genotypes indicated that peptidyl-prolyl cis-trans isomerase (A0A078IDN6 PPIase) showed high expression in resistant genotype at the early infection stage while its expression was delayed in susceptible genotypes. This study provides important insight to mustard breeders for designing effective breeding programs to develop resistant cultivars against this devastating disease.
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Planta de la Mostaza/genética , Inmunidad de la Planta , Proteoma/genética , Ascomicetos/patogenicidad , Planta de la Mostaza/metabolismo , Planta de la Mostaza/microbiología , Isomerasa de Peptidilprolil/genética , Isomerasa de Peptidilprolil/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Proteoma/metabolismoRESUMEN
This is probably the first report characterizing an extraskeletal intranasal osteoma in a Gir cow through scanning electron microscopy and various spectroscopic techniques. Nasal obstruction in a 10-year-old Gir cow is investigated in this study. Skull radiograph demonstrated 174.12 mm × 81.97 mm sized well-circumscribed radiodense mass within the left nasal passage. The intranasal mass was excised completely through a rhinotomy incision. Grossly, intranasal mass was nonhyperemic, rock-hard, and calcified, 174.12 mm × 81.97 mm in size, and 650 g of weight. Excised intranasal mass was investigated through histopathologic, scanning electron microscopic (SEM), energy-dispersive X-ray (EDX) spectroscopic, X-ray fluorescence (XRF) spectroscopic, microwave plasma-atomic energy spectroscopic (MPAES), and Fourier-transform infrared (FTIR) spectroscopic techniques. A native bone of age-matched Gir cow, collected from a cadaver, was taken as a control. Microscopically, structures similar to cortical bone randomly coexisted with trabecular bone were observed. The EDX analysis of the intranasal mass indicated mean Ca/P weight ratio of 1.88, close to Ca/P weight ratio of the control. The XRF analysis revealed the presence of Ca, P, Sr, S, Zn, Cu, Fe, and Ni in the intranasal mass. Additionally, Mn was noted by MPAES analysis. Hence, the XRF and MPAES analyses confirmed a similar elemental composition of the intranasal mass and control. FTIR spectroscopic study confirmed the presence of inorganic ν1, ν3 PO4 3- , OH- in addition to organic collagen amide A, amide B, amide I, amide II, and amide III chemical functional groups in the intranasal mass. These findings of the intranasal mass were consistent with an osteoma having similar elemental and molecular compositions with the native bone.
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Huesos , Osteoma , Animales , Bovinos , Femenino , Microscopía Electrónica de Rastreo , Espectrometría por Rayos X , Espectroscopía Infrarroja por Transformada de FourierRESUMEN
Productivity of Indian mustard, an important oilseed crop of India, is affected by several pathogens. Among them, the hemibiotroph Sclerotinia sclerotiorum, which causes sclerotinia rot disease, is the most devastating fungal pathogen causing up to 90% yield losses. The availability of host resistance is the only efficient approach to control and understand the host-pathogen interaction. Therefore, the present investigation was carried out using six Indian mustard genotypes with contrasting behavior towards sclerotinia rot to study the antioxidant resistance mechanism against S. sclerotiorum. The plants at post-flowering stage were inoculated with five-day-old pure culture of S. sclerotiorum using artificial stem inoculation method. Disease evaluation revealed significant genotypic differences for mean lesion length among the tested genotypes, where genotype DRMR 2035 was found highly resistant, while genotypes RH 1569 and RH 1633 were found highly susceptible. The resistant genotypes had more phenolics and higher activities of peroxidase, catalase and polyphenol oxidase which provide them more efficient and strong antioxidant systems as compared with susceptible genotypes. Studies of antioxidative mechanisms validate the results of disease responses.
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Stone diseases (gallstones and kidney stones) are extremely painful and often cause death. The prime aim of biomedical research in this area has been determination of factors resulting in stone formation inside the gallbladder and urinary tract. Many theories have been put forward to explain the mechanism of stone formation and their growth; however, their complete cycle of pathogenesis is still under debate. Several factors are responsible for stone formation; however, much emphasis is placed on the determination of elemental and molecular composition of the stones. In the present review article, we describe different kinds of spectroscopic techniques such as Fourier transform infrared spectroscopy (FTIR), X-ray fluorescence (XRF) spectroscopy, time-of-flight secondary ion mass spectrometry (TOF-SIMS), and laser-induced breakdown spectroscopy (LIBS) and highlight their use in the analysis of stone diseases. We have summarized work done on gallstones and kidney stones using these advanced techniques particularly over the last 10 years. We have also briefly elaborated the basics of stone formations inside the human body and their complications for a better understanding of the subject.
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BACKGROUND: Caprine skin is a promising biomaterial for tissue-engineering applications. However, tissue processing is required before its xenogenic use. AIMS: Therefore, the purpose of this study was to evaluate the structural integrity and biocompatibility of the caprine skin after de-epithelialization, using sodium chloride (NaCl) and trypsin solutions, followed by de-cellularization using sodium dodecyl sulfate (SDS) solution. MATERIALS & METHODS: The caprine skin was de-epithelialized using NaCl (2-4 mol/L) and trypsin (0.25%-0.5%) followed by the treatment of SDS (1%-4%) solution over a period of time. Acellularity of the prepared matrix was confirmed histologically and characterized by appropriate staining, scanning electron microscopy (SEM), DNA quantification, and Fourier-transform infrared (FTIR) spectroscopy. The caprine acellular dermal matrix (CADM) was used for the repair of spontaneously occurring abdominal hernia in ten buffaloes. The biocompatibility of the CADM was evaluated using clinical, hematological, biochemical, and anti-oxidant parameters. RESULTS: Histologically, the skin treated with 0.25% trypsin in 4 mol/L NaCl for 8 hours resulted in complete de-epithelialization. Further treatment with 2% SDS for 48 hours demonstrated complete acellularity and orderly arranged collagen fibers. The SEM confirmed a preservation of collagen arrangement within CADM. The DNA content was significantly (P < .05) lower in CADM (46.20 ± 7.94 ng/mg) as compared to fresh skin (662.56 ± 156.11 ng/mg) indicating effective acellularity. The FTIR spectra showed characteristic collagen peaks of amide A, amide B, amide I, amide II, and amide III in CADM. All the 10 animals recovered uneventfully and remained sound. Hematological, biochemical, and anti-oxidants findings were unremarkable. CONCLUSION: Results indicated the acceptance and biocompatibility of the xenogenic caprine acellular dermal matrix for abdominal hernia repair in buffaloes without complications.
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Dermis Acelular , Hernia Abdominal/cirugía , Ingeniería de Tejidos , Trasplante Heterólogo , Animales , Materiales Biocompatibles , Búfalos , CabrasRESUMEN
Feasibility of a simple laser-induced breakdown spectroscopy (LIBS) device has been investigated for the analysis of Mg and Ca in edible salts. The LIBS spectrometer was assembled with a compact low-power diode-pumped solid-state laser (DPSSL) and a non-gated low-resolution handheld spectrometer. A simple sampling process was employed for on-site application. A piece of filter paper was dipped in the aqueous solution of a sample salt and dried for analysis using LIBS. Maintaining the sample surface height at the optimum position was critical to generate plasmas persistently due to the low pulse energy of the DPSSL. The varying height of the filter paper surface was monitored and compensated, while the sample stage was translated to collect spectra from different positions. The variation of line intensities of Mg and Ca could be attributed to the inhomogeneous distribution of dry residues. To correct this, the peak that consists of the Na(I) and C(II) lines at 568 nm was employed as a reference signal for intensity normalization of the analyte Mg(II) and Ca(II) lines. For edible salt products, the normalized Mg(II) and Ca(II) line intensities could be well correlated with the concentrations of Mg and Ca determined using inductively coupled plasma optical emission spectroscopy. Our results indicate that a simple LIBS device in combination with the simple sampling method is promising as an on-site salt quality assessment methodology.
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Mapping of element distributions and diffusion processes in plant tissue has great significance for understanding the systematic uptake, transport, and accumulation of nutrients and harmful elements in plants, and for studying the interaction between plants and the environment. In this work, we used laser-induced breakdown spectroscopy (LIBS) to study the elemental accumulation of Li and its diffusion in plant leaves. The spatially resolved information that LIBS offers, combined with its high sensitivity to light elements make this technology highly advantageous for the analysis of Li. Laser-induced breakdown spectroscopy mapping of Li-doped leaf samples is used to directly visualize the diffusion of Li in the plant leaf and study its distribution as a function of LiCl solution exposure time. Our findings demonstrate that diffusion of Li in plant leaves occurs though their veins (i.e., bundles of vascular tissue) and that Li concentration decreases as we move away from the LiCl exposure site. These results underline the importance of veins in transportation of toxic elements in plants, and mapping of their distribution can be instrumental in the development of possible remediation approaches for managing Li toxicity.
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With the advent of improved experimental techniques and enhanced precision, laser-induced breakdown spectroscopy (LIBS) offers a robust tool for probing the chemical constituents of samples of interest in biological sciences. As the interest continues to grow rapidly, the domain of study encompasses a variety of applications vis-à-vis biological species and microbes. LIBS is basically an atomic emission spectroscopy of plasma produced by the high-power pulsed laser which is tightly focused on the surface of any kinds of target materials in any phase. Due to its experimental simplicity, and versatility, LIBS has achieved its high degree of interest particularly in the fields of agricultural science, environmental science, medical science, forensic sciences, and biology. It has become a strong and sensitive elemental analysis tool as compared to the traditional gold standard techniques. As such, it offers a handy, rapid, and flexible elemental measurement of the sample compositions, together with the added benefits of less cumbersome sample preparation requirements. This technique has extensively been used to detect various microorganisms, extending the horizon from bacteria, molds, to yeasts, and spores on surfaces, while also being successful in sensing disease-causing viruses. LIBS-based probe has also enabled successful detection of bacteria in agriculture as well. In order for good quality processing of food, LIBS is also being used to detect and identify bacteria such as Salmonella enteric serovar typhimurium that causes food contamination. Differences in soil bacteria isolated from different mining sites are a very good indicator of relative environmental soil quality. In this connection, LIBS has effectively been employed to discriminate both the inter- and intra-site differences of the soil quality across varying mining sites. Therefore, this article summarizes the basic theory and use of LIBS for identifying microbes causing serious agricultural and environmental infectious diseases.
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BACKGROUND: Topical Betamethasone (BM) and Pimecrolimus (PC) are widely used drugs in the treatment of atopic dermatitis (AD). Though the biomolecules and biological pathways affected by the drugs are known, the causal inter-relationships among these pathways in the context of skin is not available. We aim to derive this insight by using transcriptomic data of AD skin samples treated with BM and PC using systems biology approach. METHODS: Transcriptomic datasets of 10 AD patients treated with Betamethasone and Pimecrolimus were obtained from GEO datasets. We used a novel computational platform, eSkIN ( www.persistent.com/eskin ), to perform pathway enrichment analysis for the given datasets. eSkIN consists of 35 skin specific pathways, thus allowing skin-centric analysis of transcriptomic data. Fisher's exact test was used to compute the significance of the pathway enrichment. The enriched pathways were further analyzed to gain mechanistic insights into the action of these drugs. RESULTS: Our analysis highlighted the molecular details of the mechanism of action of the drugs and corroborated the known facts about these drugs i.e. BM is more effective in triggering anti-inflammatory response but also causes more adverse effect on skin barrier than PC. In particular, eSkIN helped enunciate the biological pathways activated by these drugs to trigger anti-inflammatory response and its effect on skin barrier. BM suppresses pathways like TNF and TLRs, thus inhibiting NF-κB while PC targets inflammatory genes like IL13 and IL6 via known calcineurin-NFAT pathway. Furthermore, we show that the reduced skin barrier function by BM is due to the suppression of activators like AP1 transcription factors, CEBPs. CONCLUSION: We thus demonstrate the detailed mechanistic insight into drug action of AD using a novel computational approach.
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Dermatitis Atópica/tratamiento farmacológico , Dermatitis Atópica/genética , Biología de Sistemas , Administración Tópica , Betametasona/administración & dosificación , Fármacos Dermatológicos/administración & dosificación , Humanos , Tacrolimus/administración & dosificación , Tacrolimus/análogos & derivados , TranscriptomaRESUMEN
The present study aimed to investigate the perturbations in immuno-metabolic and redox status of buffaloes with trypanosomosis. Thirteen buffaloes suffering from clinical trypanosomosis and eight apparently healthy buffaloes were included in the present study. Buffaloes with trypanosomosis found to have markedly elevated levels of interleukin-10 (IL-10), nonesterified fatty acids (NEFA) and beta-hydroxybutyrate (BHBA) in comparison with healthy controls. Whereas, total antioxidant capacity (TAC) and haemoglobin levels of buffaloes with trypanosomosis were significantly lower than the healthy controls. Remarkable elevation in malondialdehyde (MDA) and protein carbonyls (PC) levels were also observed in the diseased buffaloes. Moreover, buffaloes with trypanosomosis were found to have markedly elevated levels of serum glucose, total proteins, globulins, urea and aspartate aminotransferase (AST) and markedly lowered levels of serum calcium, total cholesterol levels and albumin/globulin (A/G) ratio as compared to the controls. Findings of our study evidently suggest that Trypanosoma evansi induces remarkable immunosuppressive and pro-oxidative status with an increased catabolic activity and hyperglycemic condition like type-2 diabetes in naturally infected buffaloes. Therefore, immuno-metabolic and pro-oxidative predicaments should be addressed by the veterinary clinician while managing the clinical cases of trypanosomosis in buffaloes.
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Diabetes Mellitus Tipo 2/inmunología , Diabetes Mellitus Tipo 2/parasitología , Trypanosoma/inmunología , Tripanosomiasis/inmunología , Tripanosomiasis/fisiopatología , Ácido 3-Hidroxibutírico/sangre , Ácido 3-Hidroxibutírico/inmunología , Animales , Antioxidantes/análisis , Análisis Químico de la Sangre , Búfalos , Diabetes Mellitus Tipo 2/etiología , Diabetes Mellitus Tipo 2/fisiopatología , Ácidos Grasos no Esterificados/sangre , Ácidos Grasos no Esterificados/inmunología , Hemoglobina A/análisis , Hiperglucemia/etiología , Hiperglucemia/parasitología , Interleucina-10/sangre , Interleucina-10/inmunología , Malondialdehído/sangre , Carbonilación Proteica , Tripanosomiasis/parasitologíaRESUMEN
HIV-1 evades host defense through mutations and recombination events, generating numerous variants in an infected patient. These variants with an undiminished virulence can multiply rapidly in order to progress to AIDS. One of the targets to intervene in HIV-1 replication is the trans-activator of transcription (Tat), a major regulatory protein that transactivates the long terminal repeat promoter through its interaction with trans-activation response (TAR) RNA. In this study, HIV-1 infected patients (n = 120) from North India revealed Ser46Phe (20%) and Ser61Arg (2%) mutations in the Tat variants with a strong interaction toward TAR leading to enhanced transactivation activities. Molecular dynamics simulation data verified that the variants with this mutation had a higher binding affinity for TAR than both the wild-type Tat and other variants that lacked Ser46Phe and Ser61Arg. Other mutations in Tat conferred varying affinities for TAR interaction leading to differential transactivation abilities. This is the first report from North India with a clinical validation of CD4 counts to demonstrate the influence of Tat genetic variations affecting the stability of Tat and its interaction with TAR. This study highlights the co-evolution pattern of Tat and predominant nucleotides for Tat activity, facilitating the identification of genetic determinants for the attenuation of viral gene expression.