Deep temporal networks for EEG-based motor imagery recognition.

The electroencephalogram (EEG) based motor imagery (MI) signal classification, also known as motion recognition, is a highly popular area of research due to its applications in robotics, gaming, and medical fields. However, the problem is ill-posed as these signals are non-stationary and noisy. Recently, a lot of efforts have been made to improve MI signal classification using a combination of signal decomposition and machine learning techniques but they fail to perform adequately on large multi-class datasets. Previously, researchers have implemented long short-term memory (LSTM), which is capable of learning the time-series information, on the MI-EEG dataset for motion recognition. However, it can not model very long-term dependencies present in the motion recognition data. With the advent of transformer networks in natural language processing (NLP), the long-term dependency issue has been widely addressed. Motivated by the success of transformer algorithms, in this article, we propose a transformer-based deep learning neural network architecture that performs motion recognition on the raw BCI competition III IVa and IV 2a datasets. The validation results show that the proposed method achieves superior performance than the existing state-of-the-art methods. The proposed method produces classification accuracy of 99.7% and 84% on the binary class and the multi-class datasets, respectively. Further, the performance of the proposed transformer-based model is also compared with LSTM.

Chemotherapy and immune check point inhibitors in the management of cervical cancer.

Management of locally advanced cervix cancer underwent major change 2 decades back when concurrent chemotherapy (CCRT) (with cisplatin alone or in combination) along with definite radiation therapy (external + brachytherapy) was found to be superior compared to radiation alone in a series of randomized trials. Since then CCRT has been the standard treatment approach; this has resulted in 5-year overall survival rate of 66% and disease-free survival (DFS) of 58%. About 30% to 40% of patients with locally advanced cervical cancer continue to have treatment failure. Also, some patients experience early and late side effects of treatment with negative impact on quality of life. To improve the outcome further - recent approaches have explored use of weekly paclitaxel and carboplatin for 4 to 6 weeks as dose dense chemotherapy prior to CCRT, adjuvant chemotherapy after CCRT in high risk patients. For patients with early stage disease (IA2-IIA), short course chemotherapy prior to surgery is associated with improved outcome in many studies. Bevacizumab- an inhibitor of vascular endothelial growth factor - is associated with improved survival. More recently, addition of treatment with immune check inhibitors (to boost the ability of T cells to destroy cancer cells) have improved responses and survival in the treatment of recurrent and metastatic cervical cancer. Whether these and other similar novel agents targeting molecular pathways could be brought in front line treatment along with cytotoxic chemotherapy along with bevacizumab are potential areas of current research.

Early-Stage epithelial ovarian cancer: Predictors of survival.

Background: One fifth of patients with epithelial ovarian cancers (EOC) present at an early stage (FIGO stage I & II). However, there is scarcity of literature on the outcomes and its predictors. The aim of the study was to assess relapse free survival (RFS), overall survival (OS) and its predictors in early stage EOC. Patients and Methods: In this retrospectively study, we included all patients with early-stage EOC diagnosed between January 2010 and December 2018. Patients with synchronous malignancies were excluded. Clinical profile, clinico-pathological characteristics and treatment details were recorded. Patient underwent initial surgery followed by adjuvant chemotherapy in high-risk disease. Patients with stage IC, or stage II or clear cell histology or high-grade histology irrespective of stage/histological subtype were defined as high-risk disease. Fertility sparing surgery (FSS) [unilateral salpingo-oopherectomy with complete surgical staging] was performed in patient willing to preserve fertility. Primary objective was to assess RFS and OS in all patients with early stage EOC. Secondary objectives were to assess RFS and OS in early stage EOC with high-risk disease, predictors of RFS and OS, and outcomes of FSS. Survival probabilities were estimated according to Kaplan-Meier and compared by the log rank test. Cox's regression model was used to analyze the significance of various factors affecting relapse free survival (RFS) and overall survival (OS). Results: 195 patients with early stage EOC were recruited with median age of 47 years (range, 16-80 years). FIGO stage I and stage II were seen in 72 % and 18 % patients respectively. Serous subtype was reported in 58 % and high-grade histology in 66 %. 184 patients (94.0%) underwent optimal staging surgery, including 27 (14%) with fertility sparing surgery (FSS). 133 (91.7 %) of 145 patients with high-risk disease received adjuvant chemotherapy (paclitaxel and carboplatin), while 12 (8.3 %) patients opted to remain on observation. At median follow up of 56 months (95 % CI, 46-64 months), 49 (25 %) patients relapsed [including 3 of 27 (11.1 %) who underwent FSS], 18 patients died of progressive disease, while 31 patients were alive and disease free. Estimated OS at 5 years is 87.6 % (95 % CI 79.9-92.5) and RFS is 73.2 % (95 % CI 64.7-80.0). On multivariate analysis tumor grade was predictive of RFS (HR 2.9, p < 0.04) and OS (HR 9.4, p < 0.02). Conclusions: This study confirms the excellent outcome for patients with early stage EOC. Histological grade of tumor is a significant predictor of OS and RFS. FSS is feasible in selected patients with early EOC.

Trabectedin in Advanced Sarcomas-Experience at a Tertiary Care Center and Review of Literature.

Background There is sparse literature on trabectedin in advanced soft-tissue sarcomas from developing world. It would be interesting to know about use and outcomes of trabectedin in Indian patients. Method In a retrospective study, consecutive patients treated with trabectedin from 2016 to 2019 were analyzed. Patients with L-sarcomas were treated at a dose of 1.5 mg/m 2 , while those with translocation-related sarcomas were treated at a dose of 1.2 mg/m 2 as a 24-hour infusion through peripherally inserted central catheter line. From July 2019, infusions were administered through an ambulatory elastomeric pump, while before that patients were admitted for 24 hours. We used SPSS version 23.0 for statistical calculation. Result A total of 20 patients received trabectedin with a total of 116 infusions. The median age was 46 years (range: 22-73 years). The male ( n = 11, 55%) and female patients were almost equal ( n = 9, 45%). Thirteen patients (65%) had Eastern Cooperative Oncology Group Performance Status 1. Majority of the patients had leiomyosarcoma ( n = 8, 40%); remaining comprised of liposarcoma (3, 15%), translocation-related sarcomas excluding myxoid liposarcoma ( n = 8, 40%) and others ( n = 1,5%). Most common site was extremity ( n = 11, 55%) followed by retroperitoneal ( n = 3, 15%), visceral ( n = 3, 15%), and others ( n = 3,15%). Median number of previous lines received was 2 (range: 0-4). Median number of trabectedin cycles received was 4 (range: 1-17). Best response assessed was stable disease ( n = 10, 50%), progressive disease ( n = 6, 30%), partial response ( n = 1, 5%), and not assessed in 3 patients. After a median follow-up of 19 months, median progression-free survival was 4 months. Conclusion In this heavily treated population (composed of L-sarcomas and translocation-related sarcomas) with many patients with poor performance status, the outcome with trabectedin is in synchrony with literature. However, the need of 24-hour admission might deter quality of life. Elastomeric pump seems to be a reasonable alternative to admission and can be a breakthrough in administering trabectedin, especially in developing countries.

Effect of nutrition-sensitive agriculture interventions with participatory videos and women's group meetings on maternal and child nutritional outcomes in rural Odisha, India (UPAVAN trial): a four-arm, observer-blind, cluster-randomised controlled trial.

BACKGROUND: Almost a quarter of the world's undernourished people live in India. We tested the effects of three nutrition-sensitive agriculture (NSA) interventions on maternal and child nutrition in India. METHODS: We did a parallel, four-arm, observer-blind, cluster-randomised trial in Keonjhar district, Odisha, India. A cluster was one or more villages with a combined minimum population of 800 residents. The clusters were allocated 1:1:1:1 to a control group or an intervention group of fortnightly women's groups meetings and household visits over 32 months using: NSA videos (AGRI group); NSA and nutrition-specific videos (AGRI-NUT group); or NSA videos and a nutrition-specific participatory learning and action (PLA) cycle meetings and videos (AGRI-NUT+PLA group). Primary outcomes were the proportion of children aged 6-23 months consuming at least four of seven food groups the previous day and mean maternal body-mass index (BMI). Secondary outcomes were proportion of mothers consuming at least five of ten food groups and child wasting (proportion of children with weight-for-height Z score SD <-2). Outcomes were assessed in children and mothers through cross-sectional surveys at baseline and at endline, 36 months later. Analyses were by intention to treat. Participants and intervention facilitators were not blinded to allocation; the research team were. This trial is registered at ISRCTN, ISRCTN65922679. FINDINGS: 148 of 162 clusters assessed for eligibility were enrolled and randomly allocated to trial groups (37 clusters per group). Baseline surveys took place from Nov 24, 2016, to Jan 24, 2017; clusters were randomised from December, 2016, to January, 2017; and interventions were implemented from March 20, 2017, to Oct 31, 2019, and endline surveys done from Nov 19, 2019, to Jan 12, 2020, in an average of 32 households per cluster. All clusters were included in the analyses. There was an increase in the proportion of children consuming at least four of seven food groups in the AGRI-NUT (adjusted relative risk [RR] 1·19, 95% CI 1·03 to 1·37, p=0·02) and AGRI-NUT+PLA (1·27, 1·11 to 1·46, p=0·001) groups, but not AGRI (1·06, 0·91 to 1·23, p=0·44), compared with the control group. We found no effects on mean maternal BMI (adjusted mean differences vs control, AGRI -0·05, -0·34 to 0·24; AGRI-NUT 0·04, -0·26 to 0·33; AGRI-NUT+PLA -0·03, -0·3 to 0·23). An increase in the proportion of mothers consuming at least five of ten food groups was seen in the AGRI (adjusted RR 1·21, 1·01 to 1·45) and AGRI-NUT+PLA (1·30, 1·10 to 1·53) groups compared with the control group, but not in AGRI-NUT (1·16, 0·98 to 1·38). We found no effects on child wasting (adjusted RR vs control, AGRI 0·95, 0·73 to 1·24; AGRI-NUT 0·96, 0·72 to 1·29; AGRI-NUT+PLA 0·96, 0·73 to 1·26). INTERPRETATION: Women's groups using combinations of NSA videos, nutrition-specific videos, and PLA cycle meetings improved maternal and child diet quality in rural Odisha, India. These components have been implemented separately in several low-income settings; effects could be increased by scaling up together. FUNDING: Bill & Melinda Gates Foundation, UK AID from the UK Government, and US Agency for International Development.

Blast resistance gene Pi54 over-expressed in rice to understand its cellular and sub-cellular localization and response to different pathogens.

Rice blast resistance gene, Pi54 provides broad-spectrum resistance against different strains of Magnaporthe oryzae. Understanding the cellular localization of Pi54 protein is an essential step towards deciphering its place of interaction with the cognate Avr-gene. In this study, we investigated the sub-cellular localization of Pi54 with Green Fluorescent Protein (GFP) as a molecular tag through transient and stable expression in onion epidermal cells (Allium cepa) and susceptible japonica cultivar rice Taipei 309 (TP309), respectively. Confocal microscopy based observations of the onion epidermal cells revealed nucleus and cytoplasm specific GFP signals. In the stable transformed rice plants, GFP signal was recorded in the stomata, upper epidermal cells, mesophyll cells, vascular bundle, and walls of bundle sheath and bulliform cells of leaf tissues. These observations were further confirmed by Immunocytochemical studies. Using GFP specific antibodies, it was found that there was sufficient aggregation of GFP::Pi54protein in the cytoplasm of the leaf mesophyll cells and periphery of the epidermal cells. Interestingly, the transgenic lines developed in this study could show a moderate level of resistance to Xanthomonas oryzae and Rhizoctonia solani, the causal agents of the rice bacterial blight and sheath blight diseases, respectively. This study is a first detailed report, which emphasizes the cellular and subcellular distribution of the broad spectrum blast resistance gene Pi54 in rice and the impact of its constitutive expression towards resistance against other fungal and bacterial pathogens of rice.

An Unusual Case of Synovial Sarcoma with Breast Metastasis: Findings on Positron Emission Tomography-Computed Tomography.

Synovial sarcomas are aggressive soft-tissue tumors with the propensity for metastases at presentation or later course of disease. The most common site of metastases is lung, followed by lymph node and bone. It rarely metastasizes to the liver and to the brain. Breast metastases from extramammary tissue are extremely rare, more so from synovial sarcoma. 18F-fluorodeoxyglucose positron emission tomography-computed tomography (FDG PET/CT) plays a very important role in diagnosing occult metastasis in sarcomas. Histopathological diagnosis and translocation studies are important to confirm the diagnosis. We present a case of synovial sarcoma who underwent 18FDG PET/CT which showed occult metastasis to the breast.

Rare actinobacteria: a potential source of bioactive polyketides and peptides.

Polyketides and peptides obtained from actinobacteria are important therapeutic compounds which include front line antibiotics and anticancer drugs. Many screening programs are directed towards isolation of bioactive compounds from these organisms but the chances of finding novel antimicrobial leads among common actinobacteria are fast dwindling. As a result, the focus has shifted to the members of less exploited genera of rare actinobacteria. Three isolates, MMS8, MMS16 and KCR3 found to be potent polyketide and peptide producers were identified by 16S rRNA gene sequencing and their sequences deposited in the GenBank under the accession numbers MG407702, MG372012 and MG430204 respectively. MMS8 identified as Micromonospora auratinigra, yielded one potent compound determined to be chloroanthraquinone with an minimum inhibitory concentration (MIC) of 8 µg/ml against Bacillus subtilis and an IC50 value of 10 µg/ml and 4 µg/ml against HeLa and IMR cell lines respectively. This is the first report of the production of chloroanthraquinone by M. auratinigra. MMS16, identified as a member of the family Micromonosporaceae, yielded a potent compound MMS16B analyzed to be a novel bafilomycin analogue. The MIC of the compound was found to be 7 µg/ml against B.subtilis and IC50 value against HeLa and IMR was observed to be 9 µg/ml and 14 µg/ml respectively. MMS16B was also found to exhibit anti-quorum sensing (AQS) activity at sublethal concentrations. KCR3 identified as Kocuria kristinae yielded a novel antimicrobial peptide with antibacterial, antifungal and AQS activity. To the best of our knowledge, no antimicrobial activity has ever been reported from K. kristinae.

Protocol for the cost-consequence and equity impact analyses of a cluster randomised controlled trial comparing three variants of a nutrition-sensitive agricultural extension intervention to improve maternal and child dietary diversity and nutritional status in rural Odisha, India (UPAVAN trial).

BACKGROUND: Undernutrition causes around 3.1 million child deaths annually, around 45% of all child deaths. India has one of the highest proportions of maternal and child undernutrition globally. To accelerate reductions in undernutrition, nutrition-specific interventions need to be coupled with nutrition-sensitive programmes that tackle the underlying causes of undernutrition. This paper describes the planned economic evaluation of the UPAVAN trial, a four-arm, cluster randomised controlled trial that tests the nutritional and agricultural impacts of an innovative agriculture extension platform of women's groups viewing videos on nutrition-sensitive agriculture practices, coupled with a nutrition-specific behaviour-change intervention of videos on nutrition, and a participatory learning and action approach. METHODS: The economic evaluation of the UPAVAN interventions will be conducted from a societal perspective, taking into account all costs incurred by the implementing agency (programme costs), community and health care providers, and participants and their households, and all measurable outcomes associated with the interventions. All direct and indirect costs, including time costs and donated goods, will be estimated. The economic evaluation will take the form of a cost-consequence analysis, comparing incremental costs and incremental changes in the outcomes of the interventions, compared with the status quo. Robustness of the results will be assessed through a series of sensitivity analyses. In addition, an analysis of the equity impact of the interventions will be conducted. DISCUSSION: Evidence on the cost and cost-effectiveness of nutrition-sensitive agriculture interventions is scarce. This limits understanding of the costs of rolling out or scaling up programs. The findings of this economic evaluation will provide useful information for different multisectoral stakeholders involved in the planning and implementation of nutrition-sensitive agriculture programmes. TRIAL REGISTRATION: ISRCTN65922679 . Registered on 21 December 2016.

Culturable rare actinomycetes from Indian forest soils: Molecular and physicochemical screening for biosynthetic genes.

BACKGROUND AND OBJECTIVES: Rare actinomycetes are a promising source of novel metabolites of pharmaceutical importance. The current study focussed on selective isolation of specific genera of rare actinomycetes and screening the isolates for biosynthetic genes particularly polyketide synthases (PKS) and non ribosomal peptide synthetases (NRPS). MATERIALS AND METHODS: The soil samples were subjected to various pre-treatments like 1.5% phenol treatment, 0.3% chloramine T treatment, benzethonium chloride treatment, etc. and plated on selective media supplemented with specific antibiotics targeting rare genera of actinomycetes. The putative rare actinomycete isolates were screened for bioactivity using agar cross streak method and agar well diffusion method. The ability of the isolates to produce anti-quorum sensing compounds was tested against Serratia marcescens. The isolates were also screened for the presence of biosynthetic gene clusters associated with PKS-I, PKS-II and NRPS pathways using the degenerate primer sets K1F-M6R, KSα/KSß and A3FA7R, respectively. The expression of these gene clusters was tracked by physicochemical screening of the extracts of isolates using spectroscopic and chromatographic techniques. RESULTS: In this study, 1.5% phenol treatment was found to be the most promising followed by heat treatment and chloramine treatment. Our studies showed that ISP5 agar was the best for isolation of rare genera followed by ISP7, Starch Caesin agar and ISP2 supplemented with antibiotics like gentamicin, nalidixic acid and streptomycin. Micromonospora was the most abundant genus followed by Dactylosporangium. Actinomadura, Nocardiopsis and Actinoplanes were almost equal in number. Primary screening showed that 92% of the isolates were active against one of the test organisms. Thirty seven isolates were found to produce anti-quorum sensing (QS) compounds. NRPS sequences were detected in thirty nine isolates (42.8%), whereas PKS-I and PKS-II sequences were detected in seventeen and twenty eight strains (18.6% and 30.7%), respectively. CONCLUSION: Nine type I and type II polyketide-producing isolates as well as six peptide-producing isolates were found. The peptide extract of isolate KCR3 and a polyketide extract of isolate NCD10 were found to possess anti-tumor activity exhibiting an IC50 value of 3 µg/ml and 2.5 µg/ml against HeLa cells.

Novel aromatic polyketides from soil Streptomyces spp.: purification, characterization and bioactivity studies.

Aromatic polyketides are important therapeutic compounds which include front line antibiotics and anticancer drugs. Since most of the aromatic polyketides are known to be produced by soil dwelling Streptomyces, 54 Streptomyces strains were isolated from the soil samples. Five isolates, R1, B1, R3, R5 and Y8 were found to be potent aromatic polyketide producers and were identified by 16S rRNA gene sequencing as Streptomyces spectabilis, Streptomyces olivaceus, Streptomyces purpurascens, Streptomyces coeruleorubidus and Streptomyces lavendofoliae respectively. Their sequences have been deposited in the GenBank under the accession numbers KF468818, KF681280, KF395224, KF527511 and KF681281 respectively. The Streptomyces strains were cultivated in the media following critically optimised culture conditions. The resulting broth extracts were fractionated on a silica gel column and preparative TLC to obtain pure compounds. The pure compounds were tested for bioactivity and the most potent compound from each isolate was identified by UV-Vis, IR and NMR spectroscopic methods. Isolated S. spectabilis (R1), yielded one potent compound identified as dihydrodaunomycin with an MIC of 4 µg/ml against Bacillus cereus and an IC50 value of 24 µM against HeLa. S. olivaceus (B1), yielded a comparatively less potent compound, elloramycin. S. purpurascens (R3) yielded three compounds, rhodomycin, epelmycin and obelmycin. The most potent compound was rhodomycin with an MIC of 2 µg/ml against B. cereus and IC50 of 15 µM against HeLa. S. coeruleorubidus (R5), yielded daunomycin showing an IC50 of 10 µM and also exhibiting antimetastatic properties against HeLa. S. lavendofoliae (Y8), yielded a novel aclacinomycin analogue with IC50 value of 2.9 µM and potent antimetastatic properties at 1 µM concentration against HeLa. The study focuses on the characterization of aromatic polyketides from soil Streptomyces spp., which can serve as potential candidates for development of chemotherapeutic drugs in future.

Immunomodulatory potential of shatavarins produced from Asparagus racemosus tissue cultures.

Medicinal properties of Asparagus racemosus (vernacular name: Shatavari) are attributed to its steroidal saponins called shatavarins. This plant is facing the threat of being endangered due to several developmental, seasonal constrains and malpractices involved in its collection and storage. To support its conservation, a tissue culture protocol is standardized which produces 20 fold higher levels of shatavarin. Here we evaluate the bioactivity and immunomodulatory potential of in vitro produced shatavarins from cell cultures of AR using human peripheral blood lymphocytes. In vitro produced shatavarin stimulated immune cell proliferation and IgG secretion in a dose dependent manner. It stimulated interleukin (IL)-12 production and inhibited production of IL-6. It also had strong modulatory effects on Th1/Th2 cytokine profile, indicating its potential application for immunotherapies where Th1/Th2 balance is envisaged. Our study demonstrating the bioactivity of tissue cultured AR extracts supports further in vivo evaluation of its immunomodulatory efficacy.

Rhodomycin analogues from Streptomyces purpurascens: isolation, characterization and biological activities.

During a screening program for bioactive natural products, a potential Streptomyces sp was isolated from soil. On the basis of biochemical, cultural, physiological and 16S rRNA gene analysis, it was identified as Streptomyces purpurascens. The isolate was grown in liquid medium and the crude antibiotic complex was obtained by ethyl acetate extraction. Seven purified fractions were obtained by preparative Thin Layer Chromatography (TLC). Acid hydrolysis of each fraction and subsequent TLC led to the identification of aglycones and sugars indicating these compounds to be Rhodomycin and its analogues. The identity of these compounds was established on the basis of UV-visible and FT-IR spectra and comparison with published data. The compounds were active against Gram-positive bacteria. Compound E, identified as Rhodomycin B, was found to be the most potent compound with an MIC of 2 µg/ml against Bacillus subtilis. Compounds A and F identified as α2-Rhodomycin II and Obelmycin respectively, and Compound E exhibited an IC50 of 8.8 µg/ml against HeLa cell line but no cytotoxicity was found against L929.