Advanced Machine Learning-Based Analytics on COVID-19 Data Using Generative Adversarial Networks.

The domain of medical diagnosis and predictive analytics is one of the key domains of research with enormous dimensions whereby the diseases of different types can be predicted. Nowadays, there is a huge panic of impact and rapid mutation of the COVID-19 virus impression. The world is getting affected by this virus to a huge extent and there is no vaccine developed so far. India is also having more than 10,000 patients with than 300 deceased. The global human community is having around 20 lacs of Coronavirus patients. The Generative Adversarial Network (GAN) is the contemporary high-performance approach in which the use of advanced neural networks is done for the cavernous analytics of the images and multimedia data. In this research work, the analytics of key points from medical images of the COVID-19 dataset is to be presented using which the diagnosis and predictions can be done for the patients. The GANs are used for the generation, transformation as well as presentation of the dataset and key points using advanced deep learning models which can analyze the patterns in the medical images including X-Ray, CT Scan, and many others. Using such approaches with the integration of GANs, the overall predictive analytics can be made high performance aware as compared to the classical neural networks with multiple layers. In this research manuscript, the inscription of work is projected on the benchmark datasets with the advanced scripting so that the predictive mining and knowledge discovery can be done effectively with more accuracy.

Genetic Architecture of Parkinson's Disease in the Indian Population: Harnessing Genetic Diversity to Address Critical Gaps in Parkinson's Disease Research.

Over the past two decades, our understanding of Parkinson's disease (PD) has been gleaned from the discoveries made in familial and/or sporadic forms of PD in the Caucasian population. The transferability and the clinical utility of genetic discoveries to other ethnically diverse populations are unknown. The Indian population has been under-represented in PD research. The Genetic Architecture of PD in India (GAP-India) project aims to develop one of the largest clinical/genomic bio-bank for PD in India. Specifically, GAP-India project aims to: (1) develop a pan-Indian deeply phenotyped clinical repository of Indian PD patients; (2) perform whole-genome sequencing in 500 PD samples to catalog Indian genetic variability and to develop an Indian PD map for the scientific community; (3) perform a genome-wide association study to identify novel loci for PD and (4) develop a user-friendly web-portal to disseminate results for the scientific community. Our "hub-spoke" model follows an integrative approach to develop a pan-Indian outreach to develop a comprehensive cohort for PD research in India. The alignment of standard operating procedures for recruiting patients and collecting biospecimens with international standards ensures harmonization of data/bio-specimen collection at the beginning and also ensures stringent quality control parameters for sample processing. Data sharing and protection policies follow the guidelines established by local and national authorities.We are currently in the recruitment phase targeting recruitment of 10,200 PD patients and 10,200 healthy volunteers by the end of 2020. GAP-India project after its completion will fill a critical gap that exists in PD research and will contribute a comprehensive genetic catalog of the Indian PD population to identify novel targets for PD.

Indian consensus on gastroesophageal reflux disease in adults: A position statement of the Indian Society of Gastroenterology.

The Indian Society of Gastroenterology developed this evidence-based practice guideline for management of gastroesophageal reflux disease (GERD) in adults. A modified Delphi process was used to develop this consensus containing 58 statements, which were generated by electronic voting iteration as well as face-to-face meeting and review of the supporting literature primarily from India. These statements include 10 on epidemiology, 8 on clinical presentation, 10 on investigations, 23 on treatment (including medical, endoscopic, and surgical modalities), and 7 on complications of GERD. When the proportion of those who voted either to accept completely or with minor reservation was 80% or higher, the statement was regarded as accepted. The prevalence of GERD in India ranges from 7.6% to 30%, being < 10% in most population studies, and higher in cohort studies. The dietary factors associated with GERD include use of spices and non-vegetarian food. Helicobacter pylori is thought to have a negative relation with GERD; H. pylori negative patients have higher grade of symptoms of GERD and esophagitis. Less than 10% of GERD patients in India have erosive esophagitis. In patients with occasional or mild symptoms, antacids and histamine H2 receptor blockers (H2RAs) may be used, and proton pump inhibitors (PPI) should be used in patients with frequent or severe symptoms. Prokinetics have limited proven role in management of GERD.

Determination of genotoxic alkyl methane sulfonates and alkyl paratoluene sulfonates in lamivudine using hyphenated techniques.

Two highly sensitive methods for the determination of genotoxic alkyl methane sulfonates (AMSs) and alkyl paratoluene sulfonates (APTSs) in lamivudine using hyphenated techniques have been presented. AMSs were determined by GC-MS method using GSBP-INOWAX (30 m×0.25 mm×0.25 µm) column. Temperature program was set by maintaining at 100 °C initially for 3 min, then rised to 220 °C at the rate of 15 °C/min and maintained at 220 °C for 16 min. N,N-dimethyl formamide was used as diluent. APTSs were determined by LC-MS using Zorbax, Rx C8, 250 mm×4.6 mm, 5 µm column as stationary phase. 0.01 M ammonium acetate is used as buffer. The mixture of buffer and methanol in 75:25 (v/v) ratio was used as mobile phase A and mixture of buffer and methanol in 5:95 (v/v) ratio was used as mobile phase B. The gradient program (T/%B) was set as 0/28, 16/50, 17/100, 23/100, 27/28 and 40/28. Both the methods were validated as per International Conference on Harmonization guidelines. Limit of quantitation was found 1.5 µg/mL for AMSs and was in the range of 1.0-1.5 µg/mL for APTSs.

Strategies for the identification, control and determination of genotoxic impurities in drug substances: a pharmaceutical industry perspective.

Regulations alarmed the control of genotoxic impurities in drug substances at lower level based on the threshold of toxicological concern and daily dose. This review explores the details of various regulations and guidances, toxicology assessment, identification of structural alerts, synthetic origins, different synthetic approaches for elimination or control, various analytical determination strategies and pharmaceutical industry concern towards genotoxic impurities.

Determination of duloxetine hydrochloride in the presence of process and degradation impurities by a validated stability-indicating RP-LC method.

A stability-indicating gradient reverse phase liquid chromatographic purity and assay method for duloxetine hydrochloride (DUH) was developed and validated. DUH was subjected to the stress conditions and it is sensitive towards oxidative, acid and hydrolytic degradation. Successful separation of DUH from its two process impurities and one degradation impurity formed under stress conditions was achieved on a Symmetry C18, 250x4.6mm, 5microm column using a gradient mixture of solvent A (0.01M potassium dihydrogen orthophosphate having 0.2% triethyl amine, pH adjusted to 2.5 with orthophosphoric acid) and solvent B (20:80 v/v mixture of acetonitrile and methanol). The flow rate is 1ml/min and the detection wavelength is 230nm. The mass balance was found to be in the range of 99.2-99.7% in all the stressed conditions.

Development and validation of a stability-indicating RP-LC method for famciclovir.

A novel stability-indicating gradient reverse phase liquid chromatographic (RP-LC) method was developed for the determination of purity of famciclovir (FCV) in presence of its impurities and degradation products. The method was developed using Inertsil ODS 3 V (250 x 4.6 mm, 5 microm) column with mobile phase containing a gradient mixture of solvent A and B. 0.01 M potassium dihydrogen orthophosphate buffer, pH adjusted to 6.0 with 1% potassium hydroxide was used as buffer. Buffer and methanol in 80:20 (v/v) ratio was used as solvent A and buffer and methanol in 20:80 (v/v) ratio was used as solvent B. The gradient program (T/%B) was set as 0/5, 15/30, 25/50, 45/60, 55/5 and 60/5. The eluted compounds were monitored at 215 nm. FCV was subjected to the stress conditions of oxidative, acid, base, hydrolytic, thermal and photolytic degradation. FCV was found to degrade significantly in oxidative, acid and base degradation conditions and mildly in hydrolytic degradation conditions and stable in thermal and photolytic degradation conditions. The degradation products were well resolved from main peak and its impurities thus proved the stability-indicating power of the method. The developed method was validated as per International Conference on Harmonization (ICH) guidelines with respect to specificity, limit of detection, limit of quantitation, precision, linearity, accuracy, robustness and system suitability. This method is also suitable for the assay of famciclovir which ranged from 99.9% to 100.2%.

Development and validation of RP-HPLC method for the determination of genotoxic alkyl benzenesulfonates in amlodipine besylate.

The present paper describes a simple isocratic reverse phase HPLC method for the determination of four genotoxic alkyl benzenesulfonates (ABSs) viz. methyl, ethyl, n-propyl and isopropyl benzenesulfonates (MBS, EBS, NPBS and IPBS) in amlodipine besylate (ADB). Good resolution between benzene sulfonic acid (BSA), MBS, EBS, NPBS, IPBS and ADB was achieved with Inertsil ODS 3V (150 mmx4.6 mm, 5 microm) column using a 65:35 (v/v) mixture of 1% triethyl amine, pH adjusted to 3.0 with orthophosphoric acid and acetonitrile as mobile phase. The flow rate was 1.0 ml/min and the elution was monitored at 220 nm. The factors involved in the method development are discussed. This method was validated as per International Conference on Harmonization (ICH) guidelines and is able to quantitate MBS, EBS, NPBS and IPBS at 21, 32, 35 and 28 ppm levels, respectively with respect to 5 mg/ml of ADB. The method is linear in range of 75-180 ppm of ABSs, which matches the range of 50-120% of estimated permitted level (150 ppm) of ABSs. ABSs were not present in the three studied pure and tablet batches of ADB.

Development and validation of GC-MS method for the determination of methyl methanesulfonate and ethyl methanesulfonate in imatinib mesylate.

A gas chromatography-mass spectrometry (GC-MS) method has been developed for the identification and determination of two carcinogenic and genotoxic mesylate esters viz. methyl methanesulfonate (MMS) and ethyl methanesulfonate (EMS) in imatinib mesylate (INM). The method was optimized based on the peak shapes and resolution of MMS and EMS. The method was validated as per International Conference of Harmonization (ICH) guidelines in terms of limits of detection (LOD), limit of quantitation (LOQ), linearity, precision, accuracy, specificity and robustness. The LOD and LOQ values were found to be 0.3 and 1.0 microg/ml, respectively. The method is linear within the range of 1-15 microg/ml for both the compounds. These mesylate esters were not found in three different batches of pure and pharmaceutical formulations of INM.

Application of oxidative coupling reactions for the estimation of ritodrine hydrochloride in bulk sample and dosage forms.

Three simple and sensitive visible spectrophotometric methods (M(1), M(2) and M(3)) have been described for the estimation of ritodrine hydrochloride (RTH) in pure state and in unit dosage forms. These are based on the oxidative coupling reaction of RTH, with 3-methyl benzothiazolione hydrazone (MBTH) in the presence of cerium 1V (Ce IV) (Method M(1)), N,N-dimethylamino-paraphenylenediamine (DMPD) in the presence of chloramine-T (CAT) (Method M(2)) and 4-aminophenazone (4-AP) in the presence of [Fe(CN(6))](3-) (Method M(3)). The variable parameters in all these methods have been optimised and the chemical reactions involved are presented. The results obtained in the three methods are statistically validated and recoveries range from 99.7 to 101.3%.

Neck mestastasis from unknown origin-results of planned primary surgery and post-operative radiation therapy.

Ninety-two patients with metastasis of unknown origin were studied between 1986 and 1997 at Kidwai Memorial Institute of Oncology, India. Treatment included planned primary radical neck dissection followed by radiotherapy. Sixty-seven patients completed our multimodal therapy. Thirty-eight of these patients had a median follow-up pf 35.7 months. Nine patients had a median follow-up of 8.3 months. Twenty patients were lost in follow-up after completing the above protocol. Twenty-five patients did not comply with prescribed therapy. Of the followed up patients 78.9% were disease free. The failure rate was 21%, which comprised of regional failure in 16% and liver metastasis in 5%. Primary manifested at base of tongue in 2 patients. In a third world cancer center like ours, advanced neck disease and unreliable follow-up mandate multimodal therapy to be instituted at the first instance. Manifest primaries should be treated on individual basis.

Age related seroprevalence of antibodies to varicella in India.

OBJECTIVE: To determine the age related prevalence of Varicella Zoster Virus (VZV) antibodies in India. SETTING: This was a cross sectional multicentric study performed in 4 major cities of India: Calcutta (outpatients), Mumbai (outpatients), Lucknow (walk-in patients to a diagnostic laboratory, orphanage and factory workers) and Bangalore (outpatients and walk-in patients to a diagnostic laboratory). METHODS: A total of 1609 volunteers from birth to 40 years of age were included into the study. IgG antibodies against VZV were determined using commercial kits (ELISA-Enzygnost). RESULTS: Overall seroprevalence of anti VZV antibodies was 68. 22percnt. The age related seroprevalence rate of anti VZV antibodies was 29percnt in the age group of 1-5 years, 51.1percnt in 5-10 years, 71.7percnt in 11-15 years, 79.8percnt in 16-20 years, 88.1percnt in 21-30 years and 91.1percnt in 31-40 years. CONCLUSION: A significant proportion of adolescents and adults are susceptible to varicella in India, as in other tropical countries

Surgical speech restoration by tracheo-oesophageal puncture--Kidwai experience.

This paper addresses our experience with primary (15 patients) and secondary (8 patients) tracheo-oesophageal puncture (TEP) in the laryngectomee. Despite a success rate of 93.3 percent in the primary TEP and 62.5 percent in secondary TEP, in a follow-up period of one month to eight years, prosthesis related problems like maintenance and recurring expenses emerged as significant deterrent factors in adopting prosthetic speech rehabilitation. Successful oesophageal speech training, increased practice of Pearson's near total laryngectomy, prior tracheostomy and advanced disease mandating post-operative radiotherapy in majority of patients are some of the factors in addition to prosthesis after-care maintenance that makes TEP a less practiced option at our center.

Functional laryngeal surgery - critical determinants of successful rehabilitation.

This study addresses the functional outcome and rehabilitative process in 30 partial laryngectomies carried out for laryngeal (22) und hypoorpharyngeal (8) cancers at the department of H/N Surgery, The kidwai Memorial Institute of Oncology. Bangalore, India from 1985-1995, Special emphasis is directed towards post-surgical convalescence after various partial laryngeetomy techniques which include 6 vertical laryngectomies (V L / VPL). 17 supraglottic laryngectomies (SG L), and 7 supracricoid laryngectomies with Cricohyoidepexy (CHP). Rehabilitative success was measured with respect to the ease of dccannulation, resumption of normal deglutition and speech analysis - both objectively using standard speech analytical equipment in a speech laboratory and subjectively using the services of blinded judges to score recorded speech of patients. The speech analysis indicate that past SGL speech was the superior most followed by V L and C H P in that order. Aspiration was deemed as minimal and inconsequential after V L/VPL followed by CHP;and SGL, in the order of severity;the extended modifications to resect the arytenoid and / or basE of tongue and / or piriform fossa faring worse than classic standard technique.

Localization of corticotropin-releasing factor in primary and secondary lymphoid organs of the rat.

Cells of the immune system produce a variety of neuropeptides or peptide hormones, either constitutively or upon induction, and possess specific neuropeptide receptors that display ligand-receptor interactions similar to those described in the central nervous system (CNS). These findings suggest that specific subsets of lymphoid cells can produce and respond to peptides previously thought to be principally neural mediators. Recently, corticotropin releasing factor (CRF) mRNA was detected in the rat thymus and spleen, although the cells that synthesize CRF were not identified. We examined the localization of CRF and its mRNA in the rat spleen, thymus, and mesenteric lymph nodes using immunocytochemistry (ICC) and in situ hybridization (ISH), respectively. Immunoreactive CRF was present in cells in the marginal zone and red pulp of the spleen, in connective tissue septa and the subcapsular region of the thymus, and in the medullary cords and sinuses of the mesenteric lymph nodes. Dual ICC/ISH for CRF and its mRNA, respectively, demonstrated CRF mRNA over CRF-immunoreactive cells, suggesting CRF synthesis. Double-label ICC for CRF and markers for specific immunocyte subsets suggest that CRF+ cells in the spleen and thymus are macrophages. CRF+ cells in primary and secondary lymphoid organs reside in compartments that are innervated by sympathetic nerves, and some cells appears to be contacted by noradrenergic sympathetic nerve fibers, suggesting that CRF release may be influenced by the sympathetic nervous system, as it is in the hypothalamo-pituitary-adrenal axis. The presence of CRF in organs of the immune system suggests that this neuropeptide may modulate immune functions after paracrine release.

Vocal rehabilitation after gastric transposition. The critical overview.

Re-establishment of effective communication following laryngopharyngo esophagectomy and gastric transposition requires thorough knowledge and flexibility of introducing the entire range of communication options. This study describes our experience with eleven patients of gastric transposition who attended intensive speech therapy and developed gastric speech using different method of speech producing and attaining various levels of proficiency. Application of digital pressure is one of the most effective technique for production of satisfactory and intelligible voice in gastric transposition cases who fail to develop speech by inhalation method.