Correlation of severity & clinical outcomes of COVID-19 with virus variants: A prospective, multicentre hospital network study.

BACKGROUND OBJECTIVES: The clinical course of COVID-19 and its prognosis are influenced by both viral and host factors. The objectives of this study were to develop a nationwide platform to investigate the molecular epidemiology of SARS-CoV-2 (Severe acute respiratory syndrome Corona virus 2) and correlate the severity and clinical outcomes of COVID-19 with virus variants. METHODS: A nationwide, longitudinal, prospective cohort study was conducted from September 2021 to December 2022 at 14 hospitals across the country that were linked to a viral sequencing laboratory under the Indian SARS-CoV-2 Genomics Consortium. All participants (18 yr and above) who attended the hospital with a suspicion of SARS-CoV-2 infection and tested positive by the reverse transcription-PCR method were included. The participant population consisted of both hospitalized as well as outpatients. Their clinical course and outcomes were studied prospectively. Nasopharyngeal samples collected were subjected to whole genome sequencing to detect SARS-CoV-2 variants. RESULTS: Of the 4972 participants enrolled, 3397 provided samples for viral sequencing and 2723 samples were successfully sequenced. From this, the evolution of virus variants of concern including Omicron subvariants which emerged over time was observed and the same reported here. The mean age of the study participants was 41 yr and overall 49.3 per cent were female. The common symptoms were fever and cough and 32.5 per cent had comorbidities. Infection with the Delta variant evidently increased the risk of severe COVID-19 (adjusted odds ratio: 2.53, 95% confidence interval: 1.52, 4.2), while Omicron was milder independent of vaccination status. The independent risk factors for mortality were age >65 yr, presence of comorbidities and no vaccination. INTERPRETATION CONCLUSIONS: The authors believe that this is a first-of-its-kind study in the country that provides real-time data of virus evolution from a pan-India network of hospitals closely linked to the genome sequencing laboratories. The severity of COVID-19 could be correlated with virus variants with Omicron being the milder variant.

Post-COVID-19 rhino-orbito-cerebral mucormycosis-A clinico-mycological study from North India.

The second wave of coronavirus disease 2019 (COVID-19), during the early 2021, lead to a devastating outbreak of mucormycosis in India. This study aimed to determine the aetiology, clinical features, comorbidities, and risk factors of rhino-orbito-cerebral mucormycosis (ROCM) and antifungal susceptibility pattern for the isolates. The study included all suspected cases of ROCM in post-COVID-19 patients attending the hospital from May to December 2021. A total of 70 patients were diagnosed with mucormycosis during the study period. The commonest presentations were rhino-orbital and rhino-orbito-cerebral in 35.7% of cases each. Diabetes mellitus was the commonest associated risk factor in 95.7% of all patients, while 78.5% of the patients were treated with corticosteroids in the recent past, and 25.7% presented with active COVID-19 pneumonia. The commonest isolate was Rhizopus arrhizus n = 14, followed by Aspergillus flavus n = 16, A. fumigatus n = 4, A. niger n = 3, Fusarium oxysporumn = 1, and Apophysomyces variabilisn = 1. Fungal species identification was done by phenotypic methods for all the isolates and DNA sequence analysis of 18 isolates, and antifungal susceptibility testing of 30 isolates was performed by commercially prepared HiMIC plate (HiMedia, Mumbai, India) using broth microdilution for amphotericin B, isavuconazole, itraconazole, voriconazole, and posaconazole. The MIC50 and MIC90 of amphotericin B for R. arrhizus strains were 0.25 and 4 µg/ml, respectively; and the MIC50 and MIC90 results for itraconazole, posaconazole, and isavuconazole were 8 and 8, 2 and 2, and 2 and 8 µg/ml, respectively. In vitro data showed that amphotericin B was the most effective antifungal against most species. The commercially available ready-to-use minimum inhibitory concentration plates are user-friendly for performing antifungal susceptibility, which may be useful in choosing appropriate regimens and monitoring emerging resistance.

Conformational effects in the vibrational and electronic spectra of propionaldehyde: Experimental and theoretical studies.

We report here investigations on conformational effects in the vibrational and electronic spectra of the propionaldehyde (propanal) molecule using FTIR (600-3200 cm-1) and vacuum ultraviolet (VUV) synchrotron radiation photoabsorption (52 500-85 000 cm-1) spectroscopy respectively. Detailed theoretical calculations (using DFT and TDDFT methodologies) on ground and excited states of the cis and gauche conformers of propanal are performed; a comprehensive spectral analysis of the IR and VUV spectra is presented. A reinvestigation of the IR spectrum reveals several new bands assigned to the gauche conformer based on theoretical calculations. The VUV spectrum exhibits rich Rydberg series structure assigned to ns, np and nd series converging to the first ionization potentials of the two conformers. Earlier assignments of the 3s cis and gauche origins are revised in addition to extending Rydberg series analysis to several higher members. Vibronic bands accompanying the 3s, 4s and 4p Rydberg states are assigned using estimated vibrational frequencies of cis and gauche conformers in the cationic ground state. Simulated potential energy curves of the first few excited states (singlets and triplets) of cis and gauche conformers of propanal help in gaining insights into photodissociation mechanisms and possible conformational effects therein.

Trends of humoral immune responses to heterologous antigenic exposure due to vaccination & omicron SARS-CoV-2 infection: Implications for boosting.

Background & objectives: Vaccination and natural infection can both augment the immune responses against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), but how omicron infection has affected the vaccine-induced and hybrid immunity is not well studied in Indian population. The present study was aimed to assess the durability and change in responses of humoral immunity with age, prior natural infection, vaccine type and duration with a minimum gap of six months post-two doses with either ChAdOx1 nCov-19 or BBV152 prior- and post-emergence of the omicron variant. Methods: A total of 1300 participants were included in this observational study between November 2021 and May 2022. Participants had completed at least six months after vaccination (2 doses) with either ChAdOx1 nCoV-19 or an inactivated whole virus vaccine BBV152. They were grouped according to their age (≤ or ≥60 yr) and prior exposure of SARS-CoV-2 infection. Five hundred and sixteen of these participants were followed up after emergence of the Omicron variant. The main outcome was durability and augmentation of the humoral immune response as determined by anti-receptor-binding domain (RBD) immunoglobulin G (IgG) concentrations, anti-nucleocapsid antibodies and anti-omicron RBD antibodies. Live virus neutralization assay was conducted for neutralizing antibodies against four variants - ancestral, delta and omicron and omicron sublineage BA.5. Results: Before the omicron surge, serum anti-RBD IgG antibodies were detected in 87 per cent participants after a median gap of eight months from the second vaccine dose, with a median titre of 114 [interquartile range (IQR) 32, 302] BAU/ml. The levels increased to 594 (252, 1230) BAU/ml post-omicron surge (P<0.001) with 97 per cent participants having detectable antibodies, although only 40 had symptomatic infection during the omicron surge irrespective of vaccine type and previous history of infection. Those with prior natural infection and vaccination had higher anti-RBD IgG titre at baseline, which increased further [352 (IQR 131, 869) to 816 (IQR 383, 2001) BAU/ml] (P<0.001). The antibody levels remained elevated after a mean time gap of 10 months, although there was a decline of 41 per cent. The geometric mean titre was 452.54, 172.80, 83.1 and 76.99 against the ancestral, delta, omicron and omicron BA.5 variants in the live virus neutralization assay. Interpretation & conclusions: Anti-RBD IgG antibodies were detected in 85 per cent of participants after a median gap of eight months following the second vaccine dose. Omicron infection probably resulted in a substantial proportion of asymptomatic infection in the first four months in our study population and boosted the vaccine-induced humoral immune response, which declined but still remained durable over 10 months.

Oxidative stress specifically inhibits replication of dengue virus.

Reactive oxygen species (ROS) are chemically active species which are involved in maintaining cellular and signalling processes at physiological concentrations. Therefore, cellular components that regulate redox balance are likely to play a crucial role in viral life-cycle either as promoters of viral replication or with antiviral functions. Zinc is an essential micronutrient associated with anti-oxidative systems and helps in maintaining a balanced cellular redox state. Here, we show that zinc chelation leads to induction of reactive oxygen species (ROS) in epithelial cells and addition of zinc restores ROS levels to basal state. Addition of ROS (H2O2) inhibited dengue virus (DENV) infection in a dose-dependent manner indicating that oxidative stress has adverse effects on DENV infection. ROS affects early stages of DENV replication as observed by quantitation of positive and negative strand viral RNA. We observed that addition of ROS specifically affected viral titres of positive strand RNA viruses. We further demonstrate that ROS specifically altered SEC31A expression at the ER suggesting a role for SEC31A-mediated pathways in the life-cycle of positive strand RNA viruses and provides an opportunity to identify drug targets regulating oxidative stress responses for antiviral development.

Neem (Azadirachta Indica A. Juss) Capsules for Prophylaxis of COVID-19 Infection: A Pilot, Double-Blind, Randomized Controlled Trial.

CONTEXT: SARS-CoV-2 is a global public-health concern. Interventions to prevent infection are urgently needed. The anti-inflammatory and antiviral effects of neem make it a potential agent for COVID-19 prophylaxis. OBJECTIVE: The study intended to evaluate the prophylactic effects of neem capsules for persons at high risk of COVID-19 infection due to contact with COVID-19 positive patients. DESIGN: The research team designed a prospective, randomized, double-blind, placebo-controlled, parallel-design study. SETTING: The study was conducted at a single center in India. PARTICIPANTS: Participants were 190 healthcare workers at the hospital or relatives of patients with COVID-19 infection. INTERVENTION: Of the 190 participants, 95 were in the intervention group and 95 in the control group. Participants received 50 mg of a proprietary, patent-pending, neem-leaf extract or a placebo orally in capsules, twice a day for 28 days. OUTCOME MEASURES: The number of individuals positive for COVID-19 between baseline and follow-up on day 56 was the primary outcome measure. Secondary measures included an evaluation of neem's safety and its effects on quality of life (QOL) and changes in biomarkers. RESULTS: The mean age of participants was 36.97 years, and 68.42% were male. Total 13 subjects tested positive during the study. All were asymptomatic. Of the 154 participants who completed the study per-protocol, 11 tested positive, 3 in the intervention group and 8 in the control group. The probability of COVID-19 infection in participants receiving the intervention was 0.45 times that of participants receiving the placebo, a relative risk of 0.45, with the effectiveness of the intervention being around 55%. Treatment-emergent adverse events (TEAEs) in both groups were minimal and were of grade 1 or 2 in severity. Biomarkers and QOL remained stable in both groups. CONCLUSIONS: The study found a reduced risk of COVID-19 infection in participants receiving neem capsules, which demonstrates its potential as a prophylactic treatment for the prevention of COVID-19 infection. The findings warrant further investigation in clinical trials.

Small-world networks of prognostic genes associated with lung adenocarcinoma development.

The present study investigates the role of network topology in lung adenocarcinoma (LUAD) development. Analysis of sex- and stage-specific whole-genome expression data revealed that co-expressed and highly connected prognostic genes common to all cancer stages form a small-world network in each stage of LUAD. These small-world networks are present within stage-specific scale-free networks, conserved across the cancer stages, and linked to cancer-specific events. The presence of small-world networks across the cancer stages presents a synchronized system in the disordered environment of cancer, resulting in the evolution of malignancy. Our study reported that these small-world networks are resilient to random and systematic attacks, indicating the least opportunity to introduce perturbations by drugs as a therapeutic intervention. We concluded that highly clustered small-world networks could be controlled through transcriptional modulation for the improved treatment of LUAD.

Grade-specific diagnostic and prognostic biomarkers in breast cancer.

An integrative approach is presented to identify grade-specific biomarkers for breast cancer. Grade-specific molecular interaction networks were constructed with differentially expressed genes (DEGs) of cancer grade 1, 2, and 3. We observed that the molecular network of grade3 is predominantly associated with cancer-specific processes. Among the top ten connected DEGs in the grade3, the increase in the expression of UBE2C and CCNB2 genes was statistically significant across different grades. Along with UBE2C and CCNB2 genes, the CDK1, KIF2C, NDC80, and CCNB2 genes are also profoundly expressed in different grades and reduce the patient's survival. Gene set enrichment analysis of these six genes reconfirms their role in metastatic phenotype. Moreover, the coexpression network shows a strong association of these six genes promotes cancer specific biological processes and possibly drives cancer from lower to a higher grade. Collectively the identified genes can act as potential biomarkers for breast cancer diagnosis and prognosis.

Role of the ATP-dependent chromatin remodeling enzyme Fun30/Smarcad1 in the regulation of mRNA splicing.

The yeast ATP-dependent chromatin remodeling enzyme Fun30 has been shown to regulate heterochromatin silencing, DNA repair, transcription, and chromatin organization. Although chromatin structure has been proposed to influence splice site recognition and regulation, whether ATP-dependent chromatin remodeling enzyme plays a role in regulating splicing is not known. In this study, we find that pre-mRNA splicing efficiency is impaired and the recruitment of spliceosome is compromised in Fun30-depleted cells. In addition, Fun30 is enriched in the gene body of individual intron-containing genes. Moreover, we show that pre-mRNA splicing efficiency is dependent on the chromatin remodeling activity of Fun30. The function of Fun30 in splicing is further supported by the observation that, Smarcad1, the mammalian homolog of Fun30, regulates alternative splicing. Taken together, these results provide evidence for a novel role of Fun30 in regulating splicing.

Antibody-based biosensor to detect oncogenic splicing factor Sam68 for the diagnosis of lung cancer.

OBJECTIVE: The present work aimed to investigate the potential utility of Sam68 protein as a prognostic marker in lung cancer. Then an electrochemical immunosensor is fabricated that is sufficiently sensitive to detect Sam68. RESULTS: Analysis of stage-specific Lung cancer microarray data shows that differential expression of Sam68 is associated with cancer stage and monotonically increases from early tumor stage to advanced metastatic stage. Moreover, the higher expression of Sam68 results in reduced survival of lung cancer patients. Based on these observations, an electrochemical immunosensor was developed for the quantification of Sam68 protein. The target protein was captured by the Anti-Sam68 antibody that was immobilized on the modified Glassy carbon electrode. The stepwise assembly process was characterized by cyclic voltammetry and electrochemical impedance spectroscopy. This fabricated immunosensor displayed good analytical performance in comparison to commercial ELISA kit with good sensitivity, lower detection limit (LOD) of 10.5 pg mL-1, and wide linear detection range from 1 to 5 µg mL-1. This method was validated with satisfactory detection of Sam68 protein in lung adenocarcinoma cell line, NCI-H23. Besides, spike and recovery assay reconfirm that the sensor can precisely quantify Sam68 protein in a complex physiological sample. CONCLUSION: We conclude Sam68 as a valuable prognostic biomarker for early detection of lung cancer. Moreover, we report the first study on the development of an electrochemical immunosensor for the detection of Sam68. The fabricated immunosensor exhibit excellent analytical performance, which can accurately predict the lung cancer patient pathological state.

Disease association of human tumor suppressor genes.

The multifactorial disease, cancer, frequently emerges due to perturbations in tumor suppressor genes (TSGs). However, a growing number of noncanonical target genes of TSGs and the highly interconnected nature of the human interactome reveal that the functions of TSGs are not limited to cancer-specific events. The various functions of TSGs lead to the assumption that cancer is linked with other human disorders. Therefore, a disease-gene association network of TSGs (TSDN) was constructed by integrating protein-protein interaction networks of TSGs (TSN) with Morbid Map in Online Mendelian Inheritance in Man. The TSDN revealed links between TSGs and 22 different human disorders including cancer and indicated disease-disease associations. In addition, high-density functional protein clusters in the TSN showed cohesive and overlapping disease-TSG associations, which proved the prevalent role of TSGs in various human diseases beyond cancer. The presence of overlapping disease-gene modules and disease-disease associations via the TSN demonstrated that other diseases can serve as possible roots of the life-threatening disease cancer. Therefore, a disease association map of TSGs could be a promising tool for exploring intricate relationships between cancer and other diseases for the early prediction of cancer and the understanding of disease etiology.

Development of an experimental set-up for low-temperature spectroscopic studies of matrix-isolated molecules and molecular ices using synchrotron radiation.

An experimental set-up for studying photophysics and photochemistry of molecules in an inert gas medium (matrix-isolated) and in the ice phase at low temperatures has been developed and commissioned at the Photophysics beamline, Indus-1 synchrotron radiation source. This end-station uses an in-house-developed closed-cycle cryostat for achieving cryo-temperatures (∼10 K). Synchrotron radiation from the Photophysics beamline is used as the source of UV-VUV photons and the system is equipped with a Fourier transform infrared spectrometer for characterization of the molecular species formed at low temperature. Various individual components of the end-station like closed-cycle cryostat, experimental chamber, gas mixing and deposition systems are tested to ascertain that the desired performance criteria are satisfied. The performance of the composite system after integration with the Photophysics beamline is evaluated by recording IR and UV-VUV photoabsorption spectra of sulfur dioxide at low temperatures (10 K), both in the ice phase as well as isolated in argon matrices. Results obtained are in good agreement with earlier literature, thus validating the satisfactory performance of the system. As an off-shoot of the study, the VUV absorption spectrum of matrix-isolated SO2 in argon matrix up to 10.2 eV is reported here for the first time. This experimental end-station will provide new opportunities to study photon-induced reactions in molecules of environmental, astrochemical and industrial importance. Details of the design, development and initial experimental results obtained are presented.

Electronic spectroscopy of ethyl bromide probed by VUV photoabsorption and quantum chemical calculations.

The electronically excited states of ethyl bromide and its deuterated isotopologue (C2H5Br and C2D5Br) are studied using synchrotron radiation based photoabsorption spectroscopy in the wavenumber region 50 000-86 000 cm-1. A detailed spectral analysis supported by quantum chemical calculations is presented. A complex Rydberg series structure comprising of nsa1, npa1, npe, nda1 and nde series, converging to each of the two spin-orbit split components of the first ionization potential (2E3/2 and 2E1/2) is observed for both the isotopologues. Quantum defect values are consistent with excitation from Br lone pair orbitals. Rydberg series analysis is extended to several higher members as compared to earlier work and corroborates the dominance of the spin-orbit mechanism over the hyperconjugative effect. A few new Rydberg series members converging to the second and third ionization potentials are observed and assigned. The complete gas phase VUV photoabsorption spectrum of C2D5Br up to its first ionization limit and its infrared absorption spectrum in the liquid phase are reported for the first time. An extended vibronic analysis of bands accompanying the first few Rydberg series is reported along with several new assignments. DFT calculations on ground states of neutral and ionic species and TDDFT calculations on singlet and triplet excited states aid and support the spectral analysis. Potential energy curves with respect to the C-Br bond length and the C-C-Br bond angle provide further insights into the nature of the excited states. This work represents a comprehensive study of the electronic absorption spectrum of ethyl bromide and its deuterated counterpart.

Spectroscopy of N,N-dimethylformamide in the VUV and IR regions: Experimental and computational studies.

The electronic absorption spectrum of N,N-dimethylformamide (DMF) is studied in the 45 000-80 000 cm-1 (5.6-9.9 eV) region using synchrotron radiation. The vacuum ultraviolet (VUV) spectrum comprises mostly of Rydberg series of ns, np, and nd types converging to the first two ionization potentials (IPs). Quantum defect values obtained are consistent with excitation of an electron from the highest occupied molecular orbitals localized on nitrogen (4a″) and oxygen (16a'); in addition, the 3s Rydberg transition converging to the third IP (3a″) is observed at 8.95 eV. A reinvestigation of the infrared spectrum of DMF in the 500-4000 cm-1 region with the help of density functional theory (DFT) calculations establishes the planarity of the ground state and leads to revision of several vibrational assignments. Vertical excited state energies and their valence/Rydberg character are predicted using time dependent DFT calculations; excellent correlation is achieved between theoretical results and experimentally observed spectral features. Potential energy curves of the first few excited states give additional insights into the nature of the excited states and their role in photodissociation dynamics. The absorption spectrum of DMF in the region >63 400 cm-1 (7.85 eV) as well as a complete set of spectral assignments in the VUV region (45 000-80 000 cm-1) is reported for the first time. This work represents a comprehensive study of the absorption spectra of DMF in the VUV and infrared regions.

Assessment of maternal vascular stiffness indices in three trimesters of normal pregnancy.

Normal pregnancy is associated with intense alterations in the maternal cardiovascular system. The aim of the present study was, to assess the influence of normal pregnancy on maternal central aortic pressures, arterial stiffness, and arterial wave reflection using non-invasive PC based cardiovascular risk analysis system (Periscope). The current study was conducted on 137 women with, normotensive, healthy, singleton pregnancies at first trimester (n = 42), second trimester (n = 48), third trimester (n = 47) of pregnancy and 35 age matched non-pregnant controls. There was no significant correlation between the estimated means for age and systolic and diastolic blood pressure. There was progressive and significant increase in BMI as pregnancy progresses (p = 0.0001). Heart rate rose significantly from Pre-pregnant to second and second to third trimesters (P < 0.003). There were no significant changes observed in central aortic diastolic pressure (AoDiaBP) as pregnancy progressed (p = 0.235) however Post Hoc comparisons showed a significant increase in central aortic systolic blood pressure (AoSysBP) and central aortic pulse pressure (AoPP) during first trimester when compared with non pregnant control group (p = 0.039 and 0.048 respectively). There was significant increase in central aortic augmentation pressure (AoAugP) in first trimester compared to non pregnant control group (p = 0.024). All the parameters of central aortic pressures were increased in the first trimester but decreased in the second trimester and again increased in the third trimester of pregnancy. There was a significant drop in Brachial-Ankle Pulse wave Velocity (baPWV) during first trimester of pregnancy compared to non-pregnant control group (p = 0.0001) after that there is a progressive increase in baPWV in second and third trimester of pregnancy. In the third trimester baPWV is increased to more than non-pregnant control group but it was non significant (p = 0.562) however it was significantly higher than first trimester (p = 0.0001). Carotid-femoral Pulse wave velocity (cfPWV) also followed the same sequence as BaPWV but the drop in cfPWV during first trimester was not significant (P = 0.135). All of the variables of hemodynamic and arterial compliance differed between participants with various trimester of pregnancy and non-pregnant control group. A significant up and down changes in Augmentation index (Aix) was observed from control to first, second and third trimester of pregnancy (3.14 to 6.74 to 2.63 to 10.51 respectively, P < 0.0001). To summarize our report show that normal pregnancy is associated with a significant cardiovascular adaptation indicated by alteration in central aortic blood pressure, augmentation index and pulse wave velocity.

Uncovering the subtype-specific disease module and the development of drug response prediction models for glioma.

The poor prognosis of glioma patients brought attention to the need for effective therapeutic approaches for precision therapy. Here, we deployed algorithms relying on network medicine and artificial intelligence to design the framework for subtype-specific target identification and drug response prediction in glioma. We identified the driver mutations that were differentially expressed in each subtype of lower-grade glioma and glioblastoma multiforme and were linked to cancer-specific processes. Driver mutations that were differentially expressed were also subjected to subtype-specific disease module identification. The drugs from the drug bank database were retrieved to target these disease modules. However, the efficacy of anticancer drugs depends on the molecular profile of the cancer and varies among cancer patients due to intratumor heterogeneity. Hence, we developed a deep-learning-based drug response prediction framework using the experimental drug screening data. Models for 30 drugs that can target the disease module were developed, where drug response measured by IC50 was considered a response and gene expression and mutation data were considered predictor variables. The model construction consists of three steps: feature selection, data integration, and classification. We observed the consistent performance of the models in training, test, and validation datasets. Drug responses were predicted for particular cell lines derived from distinct subtypes of gliomas. We found that subtypes of gliomas respond differently to the drug, highlighting the importance of subtype-specific drug response prediction. Therefore, the development of personalized therapy by integrating network medicine and a deep learning-based approach can lead to cancer-specific treatment and improved patient care.

Utility of galactomannan diagnostic assay in rhino-orbito-cerebral mycosis in COVID-19 patients.

An increasing number of fungal infections were reported post COVID-19 and many of them were caused by fungi of mixed aetiologies. This study was carried out to assess the utility of serum galactomannan (GM) assay in establishing the etiology of acute rhino-orbito-cerebral mycosis caused by Aspergillus spp. Two serum samples were obtained from 41 suspected post COVID-19 rhino-orbito-cerebral mycosis patients to perform GM assay. Serum GM assay was positive in 68.7% of the cases of proven aspergillosis at cut off OD = 1.0. Serum GM assay can be used as a supplementary test in the diagnosis of rhino-orbito-cerebral mycosis caused by Aspergillus spp.

Assessment of myocardial mechanics in overweight and obese Indian subjects.

Obesity is associated with increased cardiovascular morbidity and mortality. A direct effect of isolated obesity on cardiac function is not well established. The study was designed to determine the direct effect of various grades of isolated obesity on Echocardiographic indices of systolic and diastolic left ventricular function. Forty five overweight & obese and 30 normal weight, serving personnel without any other pathological condition were studied. Group I (n = 23) consisted of subjects with normal weight and body mass index (BMI 18.5-22.9 kg/m2), Group II (n = 28) of overweight subjects (BMI 23-24.9 kg/m2) and Group III (n = 24) of obese subjects (BMI > or = 25 kg/m2). Echocardiographic indices of systolic and diastolic function were obtained and dysfunction was assumed when at least two values differed by > or = 2 SD from the normal weight group. Ejection fraction was increased (p = 0.001) in group II and III however fractional shortening was increased significantly in group III (< 0.001). Left ventricular dimensions (EDD & ESD) were increased (P < 0.001, 0.002) but relative wall thickness was unchanged in group II & III. Systolic dysfunction was not observed in any of the obese patients. The deceleration time was increased (P < 0.01) in overweight and obese subjects compared to normal group individuals. No difference was found between obesity subgroups. Subclinical diastolic dysfunction in the form of reduced E/A ratio and increased deceleration time was more prevalent among obese subjects. BMI correlated significantly with indices of left ventricular systolic and diastolic function. Subclinical left ventricular diastolic dysfunction was noted in all grades of obesity which correlates with BMI.

DeepAutoGlioma: a deep learning autoencoder-based multi-omics data integration and classification tools for glioma subtyping.

BACKGROUND AND OBJECTIVE: The classification of glioma subtypes is essential for precision therapy. Due to the heterogeneity of gliomas, the subtype-specific molecular pattern can be captured by integrating and analyzing high-throughput omics data from different genomic layers. The development of a deep-learning framework enables the integration of multi-omics data to classify the glioma subtypes to support the clinical diagnosis. RESULTS: Transcriptome and methylome data of glioma patients were preprocessed, and differentially expressed features from both datasets were identified. Subsequently, a Cox regression analysis determined genes and CpGs associated with survival. Gene set enrichment analysis was carried out to examine the biological significance of the features. Further, we identified CpG and gene pairs by mapping them in the promoter region of corresponding genes. The methylation and gene expression levels of these CpGs and genes were embedded in a lower-dimensional space with an autoencoder. Next, ANN and CNN were used to classify subtypes using the latent features from embedding space. CNN performs better than ANN for subtyping lower-grade gliomas (LGG) and glioblastoma multiforme (GBM). The subtyping accuracy of CNN was 98.03% (± 0.06) and 94.07% (± 0.01) in LGG and GBM, respectively. The precision of the models was 97.67% in LGG and 90.40% in GBM. The model sensitivity was 96.96% in LGG and 91.18% in GBM. Additionally, we observed the superior performance of CNN with external datasets. The genes and CpGs pairs used to develop the model showed better performance than the random CpGs-gene pairs, preprocessed data, and single omics data. CONCLUSIONS: The current study showed that a novel feature selection and data integration strategy led to the development of DeepAutoGlioma, an effective framework for diagnosing glioma subtypes.

Patterns and predictors of female sexual dysfunction in diabetes mellitus.

Background Sexual complications of people with diabetes mellitus (DM) are often neglected by the patients as well as clinicians. The neglect is more in women due to the associated stigma and taboo. Indian studies are scanty, varied and inconsistent, regarding the impact of DM on sexual functioning in women. We studied the patterns and predictors of sexual dysfunction in women with DM. Methods We did a cross-sectional questionnaire-based study comprising 50 participants in both the study (women with DM1 and DM2) and control groups (relatives/caregivers of patients and the hospital staff), selected randomly from the medicine outpatient department from May to August 2016. Approval from the institutional ethics committee was obtained. Clinical anxiety and depression were screened using the hospital anxiety and depression scale. Sexual dysfunction was assessed through female sexual function index scale (FSFI), and predictors were assessed by correlating FSFI scores with sociodemographic and clinical parameters. Results We found that 44% of women with DM had sexual dysfunction compared with 20% in the control group (p<0.01). The pattern of sexual dysfunction was seen across the domains of desire, arousal, lubrication and orgasm. High body mass index, higher age, duration of DM, treatment with insulin and complications of DM predicted a greater degree of sexual dysfunction among women. Conclusion Sexual dysfunction is common in women with DM, irrespective of the type of DM and coexisting psychological factors such as depression and anxiety.