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Abstract Creatine chemical exchange saturation transfer (CrCEST) MRI is an emerging high resolution and noninvasive method for measuring muscle specific oxidative phosphorylation (OXPHOS). However, CrCEST measurements are sensitive to changes in muscle pH, which might confound the measurement and interpretation of creatine recovery time (τCr). Even with the same prescribed exercise stimulus, the extent of acidification and hence its impact on τCr is expected to vary between individuals. To address this issue, a method to measure pH pre- and post-exercise and its impact on CrCEST MRI with high temporal resolution is needed. In this work, we integrate carnosine 1H- magnetic resonance spectroscopy (MRS) and 3D CrCEST to establish “mild” and “moderate/intense” exercise stimuli. We then test the dependence of CrCEST recovery time on pH using different exercise stimuli. This comprehensive metabolic imaging protocol will enable personalized, muscle specific OXPHOS measurements in both healthy aging and myriad other disease states impacting muscle mitochondria.

Abstract The ability to electrically manipulate antiferromagnetic magnons, essential for extending the operating speed of spintronic devices into the terahertz regime, remains a major challenge. This is because antiferromagnetic magnetism is challenging to perturb using traditional methods such as magnetic fields. Recent developments in spin-orbit torques have opened a possibility of accessing antiferromagnetic magnetic order parameters and controlling terahertz magnons, which has not been experimentally realised yet. Here, we demonstrate the electrical manipulation of sub-terahertz magnons in the α-Fe2O3/Pt antiferromagnetic heterostructure. By applying the spin-orbit torques in the heterostructure, we can modify the magnon dispersion and decrease the magnon frequency in α-Fe2O3, as detected by time-resolved magneto-optical techniques. We have found that optimal tuning occurs when the Néel vector is perpendicular to the injected spin polarisation. Our results represent a significant step towards the development of electrically tunable terahertz spintronic devices.

Advanced Non-Small Cell Lung Carcinoma (NSCLC) patients with ROS1 gene rearrangement have shown significant therapeutic responses to tyrosine kinase inhibitors approved by the US Food and Drug Administration, with approximately 40 fusion partners documented in the existing literature. Our report highlights a novel fusion partner of ROS1 that has demonstrated a conclusive response to the current standard of treatment.

Abstract Background We evaluated whether an abundance of first‐trimester plasma mitochondrial DNA (mtDNA) fragments could predict the risk for the development of gestational diabetes mellitus (GDM) by the late second or early third trimester. Methods It was a prospective study wherein we enrolled 150 women in their first trimester of gestation. Oral glucose tolerance test (OGTT) was administered both in the first and second trimesters to diagnose GDM. Results Among our cohort, 23 women were diagnosed with GDM in the first trimester and excluded from the study. Of the remaining 127, 29 women were diagnosed with GDM in the second trimester, and 98 women who did not develop GDM served as controls. We amplified blood drawn from each participant during the first trimester for three distinct mtDNA gene sequences: COX, ND4, and D‐loop. An abundance of each mtDNA sequence, estimated by the ΔCt method between mtDNA and 18S rRNA, correlated with GDM occurrence in the late second or early third trimester. There was a significant difference in ΔCt COX between controls and those with GDM occurrence in the second trimester (p = .006). These levels were not associated with age or fasting plasma glucose levels in the first trimester. ΔCt COX could predict GDM with a sensitivity of 90% and a specificity of 40%. Though ΔCt ND4 was higher in the GDM‐positive group, the levels did not reach statistical significance. ΔCt D‐loop was similar in GDM‐positive cases and controls who did not develop GDM during pregnancy. Conclusions These results were in plasma samples collected 3 to 4 months before overt hyperglycemia diagnosis suggestive of GDM. The abundance of plasma mtDNA fragments represents a promising cost‐effective, convenient early‐stage biomarker for predicting GDM development. Importantly, it can be administered irrespective of the fasting status of the subject. Further assessment of the predictive capacity of these biomarkers within large, diverse populations is needed for effective clinical utility.

In this paper, I intend to propound that Socrates’ choice of abstaining himself from writing not only leads to the “Socratic Problem” but also renders him vulnerable to misappropriations; a vulnerability he attributes to writing while substantiating his downright dismissal of it. The paper has been divided into three sections. In section one; effort is to contemplate “The Socratic Problem” which has been baffling scholars across centuries. Whether, for example, in Plato’s works, is it Plato’s or the historical Socrates’ views? Absence of Socrates’ own work has put his historical existence in a blurry picture and his character under shadows of doubts. In section two, there is an attempt to outline the debate between Phonocentrism and Oral tradition. Socrates is seen projecting phonocentric viewpoints in Plato’s Phaedrus, when he censures writing by invoking an Egyptian myth. In the last section, I have put forth a surmise that Plato’s Socrates must be an apotheosized and misappropriated version of the historical Socrates. And I question, if it can be taken as an insinuation that we need to consider possibility of misappropriation every time we read history without historicity.

Abstract Alzheimer's disease is a type of progressive neurological disorder which is irreversible and the patient suffers from severe memory loss. This disease is the seventh largest cause of death across the globe. As yet there is no cure for this disease, the only way to control it is its early diagnosis. Deep Learning techniques are mostly preferred in classification tasks because of their high accuracy over a large dataset. The main focus of this paper is on fine‐tuning and evaluating the Deep Convolutional Networks for Alzheimer's disease classification. An empirical analysis of various deep learning‐based neural network models has been done. The architectures evaluation includes InceptionV3, ResNet with 50 layers and 101 layers and DenseNet with 169 layers. The dataset has been taken from Kaggle which is publicly available and comprises of four classes which represents the various stages of Alzheimer's disease. In our experiment, the accuracy of DenseNet consistently improved with the increase in the number of epochs resulting in a 99.94% testing accuracy score better than the rest of the architectures. Although the results obtained are satisfactory, but for future research, we can apply transfer learning on other deep models like Inception V4, AlexNet etc., to increase accuracy and decrease computational time. Also, in future we can work on other datasets like ADNI or OASIS and use Positron emitted tomography, diffusion tensor imaging neuroimages and their combinations for better result.

The evaluation of different mango varieties was conducted during 2019-20 and 2020-21. The experiment was laid out in a randomized block design (RBD) with four varieties, namely, Ambika, Pusa Arunima, Kesar, and Dashehari-51, each replicated three times. The plants were spaced at 4x4 m intervals. The results obtained demonstrated significant variations in various parameters, ranging from minimum to maximum values. The canopy spread ranged from 1.77 to 7.49 m, stem girth from 16.67 to 40 cm, number of fruits per plant from 21 to 118, fruit length from 92.04 to 123.28 mm, fruit width from 56.02 to 77.41 mm, and fruit weight from 202 to 591 g. However, the number of primary branches (2-3) and plant height (1.54-4.35 m) were found to be nonsignificant. Based on the morpho-economic traits, Pusa Arunima appeared to be a superior variety in terms of tree morpho-economic traits, while others were considered moderate. Considering the average number of fruits per plant and fruit weight (g) over a two-year period, Pusa Arunima clearly outperformed the other three varieties in terms of yield. Furthermore, Pusa Arunima, Kesar, and Ambika exhibited more marketable fruit traits. These findings emphasize the significant diversity among the examined mango cultivars. Therefore, it is crucial to protect and preserve these valuable genetic resources for future breeding programs aimed at developing novel and commercially viable cultivars.

Non-invasive methods of detecting early-stage Alzheimer’s disease (AD) can provide valuable insight into disease pathology, improving the diagnosis and treatment of AD. Nuclear Overhauser enhancement (NOE) MRI is a technique that provides image contrast sensitive to lipid and protein content in the brain. These macromolecules have been shown to be altered in Alzheimer’s pathology, with early disruptions in cell membrane integrity and signaling pathways leading to the buildup of amyloid-beta plaques and neurofibrillary tangles. We used template-based analyzes of NOE MRI data and the characteristic Z-spectrum, with parameters optimized for increase specificity to NOE, to detect changes in lipids and proteins in an AD mouse model that recapitulates features of human AD. We find changes in NOE contrast in the hippocampus, hypothalamus, entorhinal cortex, and fimbria, with these changes likely attributed to disruptions in the phospholipid bilayer of cell membranes in both gray and white matter regions. This study suggests that NOE MRI may be a useful tool for monitoring early-stage changes in lipid-mediated metabolism in AD and other disorders with high spatial resolution.

This study reports the common problems of weed species that adversely affect the crop productivity of the agriculture crops at a large scale. The purpose of this study is to investigate the impact of dried application of Chenopodium murale and Coronopus didymus on seed germination and early growth of Hordeum vulgare. The experiment was performed in a randomised block design with three replications under the greenhouse condition in pot culture. Shoots and roots materials were separately dried in shade for 15–20 days, dry powdered shoot and root residues of C. murale and C. didymus were applied at 5 and 10g kg-1 doses to barley seeds in 6” pots with control for three weeks. C. didymus (10g) shoot residues were most inhibitive against germination (31.16%), GVI (0.85), SVI (4.90) and leaf area (3.94 cm2) of barley while 5 g root residues of the weed had least pronounced effect. Root length, shoot length, and dry biomass were most inhibited by C. murale 10 g in both shoot and root residue treatments. Shoot residues were more inhibitive of germination and growth than root residues of both weeds. Chlorophyll accumulation patterns showed mixed results with some treatments even stimulating their concentrations. Root treatments were in general more inhibitive than shoot treatments. All treated seedlings exhibited higher levels of proline accumulation compared to control. At lower dose, C. murale treatments were more inhibitive than C. didymus treatments. There is a great scope of research on these species to isolate and identify the active factors and also to understand their implication in the biocontrol of weeds apart from their potential negative effects on agricultural crops, especially cereal crops, which can be useful to increasing crop production in northern India, namely in Uttar Pradesh

Abstract Urbanization is expected to hold about 50% of the world population by 2050 and there will be stress on available resources including food and freshwater. Further, inefficient utilization of irrigation water possesses additional challenges and it is predicted that by 2050, India will face shortage of freshwater resources. Urban agriculture and Precision Agriculture are the possible solutions in smart cities for the predicted challenges providing food security and safety, sustainable life in cities. Internet of Things (IoT) and Machine Learning (ML) are the possible solutions to smart cities' farming. Agricultural activities such as irrigation of plants, rain and drought conditions monitoring supported by IoT and ML succour farmers to righteous decision on agriculture activities. A detailed study is carried out on the role, opportunities, and different aspects of smart cities, urban farming, communication technologies, IoT and ML with respect to agriculture. The article presents the design of intelligent irrigation system based on soil and weather conditions. The soil and weather parameters are selected through various research articles in Agriculture 4.0 and ML. The article also juxtapositions the designed weather station with the various patents developed. The system developed in this article provides a cost‐effective and state‐of‐the‐art solution to local weather monitoring.

Abstract Water decontamination became a priority-based focused area for environmental scientists and researchers these days. Several contaminants like pesticides (chlorpyrifos, endosulfan, aldrin, lindane, malathion) and heavy metals (As, Pb, Cd, Hg, Cu) are broadly reported in drinking water worldwide. Pesticides and heavy metals build up in drinking water is a danger to all consumers. These pollutants cause a number of deadly diseases like bone deformity, nerve disorder, liver damage and cancer. So, their elimination from drinking water is a must to do thing to save life of the living creatures. Several pollutant removal processes are applied for the eliminations of these contaminants from water, of which adsorption and photocatalysis are latest, effective and focused in this paper. Thus, this review will focused on the recent work done using zinc and iron oxides nanomaterials as adsorbent for the removal of different heavy metals and photocatalysts for the mineralization of various pesticides.

Purpose: To determine the incidence of vitreous loss and visual outcome after a vitreous loss during cataract surgery performed by surgeons with various levels of experience in adults >40 years of age at a tertiary eye care center in North India. Methods: The study was conducted at a tertiary eye care center in North India. This was an observational, retrospective, cross-sectional study of patients who underwent cataract surgery from August 1, 2011 to July 31, 2014. All adult cataract cases who were operated on from August 1, 2011 to July 31, 2014 and who experienced vitreous loss during their surgery were included in the study. The visual outcomes of these patients who experienced vitreous loss during cataract surgery in uncomplicated cataract and were managed using standard automated vitrectomy techniques were assessed for different cataract surgical techniques (extracapsular, small-incision, and phacoemulsification) as well as at different levels of skill of the operative surgeon (consultant, short term fellow, and long-term fellow). Details of the postoperative period and best-corrected visual acuity (BCVA) were collected from patient records by the principal investigator on day 1, 1 week, 4 weeks, 6 weeks, and 3 months post cataract surgery. Results: Vitreous loss occurred in 374 out of 18,430 patients who underwent cataract surgery from August 1, 2011 to July 31, 2014. The overall incidence of vitreous loss in our study was found to be 2.03% with consultants having a rate of 1.66%, short-term fellows at 5.19%, and long-term fellows at 2.02%. Two hundred eighty-eight patients of the 374 cases followed up for 3 months at the hospital and 75.69% of these patients had a final visual acuity of ≥6/18. Conclusion: In an institute with a structured training program for residents/trainees, the vitreous loss rate is low during cataract surgery. Early intervention and proper management with the standard microsurgical technique by experienced hands can improve the final visual outcome in eyes with vitreous loss. Cystoid macular edema and corneal edema were the most common causes of poor postoperative vision.

Background: Ayurveda, the indigenous medical system of India, has chemosensory property (rasa) as one of its major pharmacological metric. Medicinal plants have been classified in Ayurveda under six rasas/tastes—sweet, sour, saline, pungent, bitter and astringent. This study has explored for the first time, the use of Electronic tongue for studies of rasa-based classification of medicinal plants.Methods: Seventy-eight medicinal plants, belonging to five taste categories (sweet, sour, pungent, bitter, astringent) were studied along with the reference taste standards (citric acid, hydrochloric acid, caffeine, quinine, L-alanine, glycine, β-glucose, sucrose, D-galactose, cellobiose, arabinose, maltose, mannose, lactose, xylose). The studies were carried out with the potentiometry-based Electronic tongue and the data was analysed using Principle Component Analysis, Discriminant Function Analysis, Taste Discrimination Analysis and Soft Independent Modeling of Class Analogy.Results: Chemosensory similarities were observed between taste standards and the plant samples–citric acid with sour group plants, sweet category plants with sucrose, glycine, β-glucose and D-galactose. The multivariate analyses could discriminate the sweet and sour, sweet and bitter, sweet and pungent, sour and pungent plant groups. Chemosensory category of plant (classified as unknown) could also be identified.Conclusion: This preliminary study has indicated the possibility of fingerprinting the chemosensory-based ayurvedic classification of medicinal plants using E-tongue coupled with multivariate statistical analysis.

Small Cell Carcinoma of the Ovary-Hypercalcemic Type (SCCOHT) is an aggressive tumor that affects young females, typically in the second decade of life. The patients with SCCOHT harbor somatic or germline mutations in the SMARCA4 gene. Germline mutations cause Rhabdoid Tumor Predisposition Syndrome (RTPS) type 2. The median age of diagnosis of RTPS is four to seven months, and most cases of RTPS are diagnosed before reaching two years of age. RTPS2 predisposes the female carrier to an ill-defined risk of developing SCCOHT before attaining puberty. We report a case of SCCOHT in an 18-year-old female, considerably later than inherited SCCOHT, with a novel deleterious germline mutation in SMARCA4.

Background A mutation/deletion involving donor or acceptor sites for exon 14 results in splicing out of exon 14 of the mesenchymal epithelial transition (MET) gene and is known as “MET exon 14 skipping” (ΔMET14). The two recent approvals with substantial objective responses and improved progression-free survival to MET inhibitors namely capmatinib and tepotinib necessitate the identification of this alteration upfront. We herein describe our experience of ΔMET14 detection by an mRNA-based assay using polymerase chain reaction followed by fragment sizing. Methods This is a home brew assay which was developed with the concept that the transcripts from true ΔMET14 will be shorter by ~140 bases than their wild type counterparts. The cases which were called MET exon 14 skipping positive on next-generation sequencing (NGS) were subjected to this assay, along with 13 healthy controls in order to establish the validity for true negatives. Results Thirteen cases of ΔMET14 mutation were detected on NGS using RNA-based sequencing. Considering NGS as a gold standard, the sizing assay using both gel and capillary electrophoresis that showed 100% specificity for both with concordance rates of 84.6% and 88.2% with NGS, respectively, were obtained. Conclusions Owing to the cost-effective nature and easy to use procedures, this assay will prove beneficial for small- and medium-sized laboratories where skilled technical personnel and NGS platforms are unavailable.

Considering the economic significance of S. dorsalis in chilli crop, a study was carried out at the ICAR-Research Complex for Eastern Region, Farming System Research Centre for Hill and Plateau Region, Ranchi, Jharkhand during the spring season of 2019 and 2020 to find out the effective chemical molecules for managing this pest. Effectiveness of 8 modern insecticides against S. dorsalis and their effect on coccinellid predators was evaluated. Efficacy of insecticides was determined by comparing number of thrips, immature stages and adults of natural enemies, marketable yield in insecticide treated versus untreated control plots. Application of spinosad @70 g a.i./ha, Emamectin benzoate 5 sg @11 g a.i./ha, Imidacloprid 200 sl @40 g a.i./ha and Fipronil 5 sc @30 g a.i./ha were found to be effective against S. dorsalis in chilli. Other insecticides were inconsistent in effectiveness against S. dorsalis population. Fenpropathrin followed by Imidacloprid were found to cause maximum reduction and Spinosad and Emamectin benzoate caused lowest reduction of coccinellid population. Thus, based on the present study, Spinosad, Emamectin benzoate, Fipronil and Imidacloprid are recommended to manage S. dorsalis on rotational basis in chilli ecosystem.

Abstract Aims Skeletal muscle (SkM) abnormalities may impact exercise capacity in patients with heart failure with preserved ejection fraction (HFpEF). We sought to quantify differences in SkM oxidative phosphorylation capacity (OxPhos), fibre composition, and the SkM proteome between HFpEF, hypertensive (HTN), and healthy participants. Methods and results Fifty‐nine subjects (20 healthy, 19 HTN, and 20 HFpEF) performed a maximal‐effort cardiopulmonary exercise test to define peak oxygen consumption (VO2, peak), ventilatory threshold (VT), and VO2 efficiency (ratio of total work performed to O2 consumed). SkM OxPhos was assessed using Creatine Chemical‐Exchange Saturation Transfer (CrCEST, n = 51), which quantifies unphosphorylated Cr, before and after plantar flexion exercise. The half‐time of Cr recovery (t1/2, Cr) was taken as a metric of in vivo SkM OxPhos. In a subset of subjects (healthy = 13, HTN = 9, and HFpEF = 12), percutaneous biopsy of the vastus lateralis was performed for myofibre typing, mitochondrial morphology, and proteomic and phosphoproteomic analysis. HFpEF subjects demonstrated lower VO2,peak, VT, and VO2 efficiency than either control group (all P

Background: Although Electronic tongue is used in pharmaceutical, food and beverage industries for objective evaluation of taste, its use in medicinal plants from an ayurvedic perspective is novel. Control experiments are therefore necessary to standardise and optimise parameters. Objective: The aim is to optimise the use of solvent and standardise sample concentration for study of plants from an ayurvedic standpoint of rasa. The major objectives are two-fold: (i) evaluate sensor response to different types of solvent water (ii) explore use of E-tongue in taste ranking of medicinal plants used in ayurveda. Materials and methods: Single, double and triple distilled, reverse osmosis and milliQ waters were evaluated separately and as a medium for preparing plant extracts. For taste ranking, standard addition method using d-glucose as sweet taste standard was used for different brands of mango juices (case in point study) and eight medicinal plants from sweet category. The effect of sample concentration and taste standard on taste ranking were evaluated. Results: MQ and TD water demonstrated similar organoleptic properties whereas plant extracts prepared in DD and MQ water showed maximum taste-based differentiation. The mango juices were taste discriminated by E-tongue and ranked based on their sweetness scores. The relative ranking of plant samples showed concentration dependence and also varied with the concentration range of taste standard. Conclusion: Milli-Q and double distilled water can be used for E-tongue studies of medicinal plants. While the results open up the possibility of taste ranking of medicinal plants, they also demonstrate the importance of standardising and optimising the concentration of samples and taste standards in the context of ayurvedic rasa based studies.

There is growing interest in understanding how ayurveda, the indigenous medical system of India, uses plants for therapeutic purpose. The aim of this two parts article is to explore how the analytical technique of Electronic tongue (E-tongue) can be used for studying rasa, one of the major ayurvedic parameter in the study of medicinal and nutritional plants. Although E-tongue is widely used in pharmaceutical, food and beverage industries for objective evaluation of taste, its use in plants from an ayurvedic perspective is novel. This first of the two parts article introduces the technique of E-tongue, positioning it in context for the following part. The latter discusses crucial control experiments required prior using E-tongue for studies on medicinal plants from an ayurvedic standpoint.

Introduction: Perforation peritonitis is a fairly common surgical problem. Despite recent advances in surgical practice, postoperative minor and major complications are common in patients of peritonitis. Intraoperative peritoneal lavage is an important operative management and the choice of fluid can affect the outcome. Aim: To compare the outcomes of peritoneal lavage using normal saline versus metronidazole in cases of perforation peritonitis in patients undergoing laparotomy, with respect to surgical site infections, sepsis, wound dehiscence, hospital stay. Materials and Methods: The present study was a longitudinal study done on 80 patients, divided in two groups with 40 cases in each group. In one group, peritoneal cavity was lavaged with 2 L of normal saline and closed after putting drains. In the other group, peritoneal cavity was lavaged with 2 L normal saline mixed with 100 mL (500 mg) of metronidazole and abdomen was closed in layers after placing two drains, kept closed for one hour after abdominal closure. Chi-square test was used, and p

Abstract Background Concurrent chemoradiotherapy followed by brachytherapy is the standard of care in locally advanced carcinoma cervix. There is no prognostic factor at present to predict the outcome of disease in locally advanced carcinoma cervix. Aim Differential expression of microRNAs can be used as biomarkers to predict clinical response in locally advanced carcinoma cervix patients. Methods Thirty‐two patients of locally advanced carcinoma cervix with International Federation of Gynecology and Obstetrics Stage IB‐IVA were enrolled from 2017 to 2018. Expression of microRNA‐9 5p, ‐31 3p, ‐100 5p, ‐125a 5p, ‐125b‐5p, and –200a 5p in formalin‐fixed paraffin embedded (FFPE) biopsied tissue were analyzed by real time quantitative reverse transcriptase polymerase chain reaction (RT qPCR). Pretreatment evaluation was done with clinical examination and MRI pelvis. All patients received concurrent chemoradiotherapy followed by brachytherapy. Patients were evaluated for the clinical response after 3 months of treatment, with clinical examination and MRI pelvis scan using RECIST 1.1 criteria. Patients with no residual disease were classified as Complete responders (CR) and with residual or progressive disease were classified as Nonresponders (NR). Results were statistically analyzed using Mann Whiney U test to examine significant difference between the expression of microRNA between complete responders (CR) and nonresponders (NR). Results microRNA‐100 5p was upregulated in complete responders (CR) which showed a trend towards statistical significance (p value = 0.05). Conclusion microRNA‐100 5p can serve as a potential molecular biomarker in predicting clinical response to chemoradiation in locally advanced Carcinoma cervix. Its role should be further investigated in a larger study population.

Megakaryocytes (MKs), the largest cells in the bone marrow, are generated from hematopoietic stem cells (HSCs) in a sequential process called megakaryocytopoiesis in which HSCs undergo MK-progenitor (MP) commitment and maturation to terminally differentiated MK. Megakaryocytopoiesis is controlled by a complex network of bone marrow niche factors. Traditionally, the studies on megakaryocytopoiesis were focused on different cytokines, growth factors and transcription factors as the regulators of megakaryocytopoiesis. Over the past two decades many research groups have uncovered the key role of microRNAs (miRNAs) in megakaryocytopoiesis. miRNAs are a class of small length non-coding RNAs which play key regulatory role in cellular processes such as proliferation, differentiation and development and are also known to be involved in disease development. This review summarizes the current state of knowledge of miRNAs which have changed expression during megakaryocytopoiesis, also focuses on miRNAs which are differentially regulated during developmental maturation of MKs. Further, we aimed to discuss potential mechanisms of miRNAs-mediated regulation underlying megakaryocytopoiesis and developmental maturation of MKs.

Abstract We find the symmetry algebras of cosets which are generalizations of the minimal-model cosets, of the specific form SU N k × SU N ℓ SU N k + ℓ $$ \frac{\mathrm{SU}{(N)}_k\times \mathrm{SU}{(N)}_{\mathrm{\ell}}}{\mathrm{SU}{(N)}_{k+\mathrm{\ell}}} $$ . We study this coset in its free field limit, with k, ℓ → ∞, where it reduces to a theory of free bosons. We show that, in this limit and at large N, the algebra W ∞ e 1 $$ {\mathcal{W}}_{\infty}^e\left[1\right] $$ emerges as a sub-algebra of the coset algebra. The full coset algebra is a larger algebra than conventional W $$ \mathcal{W} $$ -algebras, with the number of generators rising exponentially with the spin, characteristic of a stringy growth of states. We compare the coset algebra to the symmetry algebra of the large N symmetric product orbifold CFT, which is known to have a stringy symmetry algebra labelled the ‘higher spin square’. We propose that the higher spin square is a sub-algebra of the symmetry algebra of our stringy coset.

H2B monoubiquitination is implicated in oncogenesis. Here, the authors show that UBR7 PHD finger is a H2BK120 monoubiquitin ligase that acts a tumour suppressor in breast cancer by suppressing gene expression for EMT, while promoting expression of CDH4 which restrain WNT/β-cat pathway.

Voltage control of spin-orbit torques (SOTs) provides additional degrees of freedom for spinmemory and -logic applications. Here the authors demonstrate a large voltage control of direction as well as amount of current-induced spin accumulation at the heavy metal/ferromagnet interface and effectively tune the SOTs in a Pt/Co/GdOx heterostructure.

Light chain myeloma (LCM) has a reported worldwide incidence of approximately 15%–20% among all multiple myeloma (MM) patients. Few western studies have shown strong correlation of LCM with anemia, higher International Staging System scores, proclivity to renal failure, elevated lactate dehydrogenase levels, raised serum-free light chain ratio, higher frequency of extramedullary plasmacytomas, and poorer overall survival, attributable probably to lack of differentiation and skeletal destruction. The primary aim of this retrospective observational study was to define the clinical and hematological characteristics as well as prognostic outcome of Indian LCM patients in comparison with the IgG and IgA subtypes. Patients were defined according to the International Myeloma Working Group diagnostic criteria 2016 and staged as per the International Staging System. Out of 104 patients of newly diagnosed MM in which results of serum immunofixation (IFE) were available, 65 were of IgG isotype (62.5%), 15 had IgA (14.4%), and 24 had light chain myelomas (LCMs) (23.1%). It was observed that LCM patients significantly correlated with hypercalcemia and higher serum-free light chain ratios, whereas IgA patients were strongly associated with anemia and lower serum albumin levels. However, no difference was found among the three subgroups in terms of serum lactate dehydrogenase levels, proclivity to renal failure, presence of lytic bone lesions, prognostic scoring, pretransplant chemosensitivity, and progession-free survival (1 year). Thus, it may be concluded that Indian LCM patients have significantly different clinico-hematological profile in comparison with other published studies worldwide. Also, their prognostic outcomes are not worse when compared with patients of other protein isotypes, probably due to standardized treatment regimens applied.

Quantitative MRI modalities, such as diffusion tensor imaging (DTI) or magnetization transfer imaging (MTI) are sensitive to the neuronal effects of aging of the cerebral white matter (WM), but lack the specificity for myelin content. Myelin water imaging (MWI) is highly specific for myelin and may be more sensitive for the detection of changes in myelin content inside the cerebral WM microstructure. In this multiparametric imaging study, we evaluated the performance of myelin water fraction (MWF) estimates as a marker for myelin alterations during normal-aging. Multiparametric MRI data derived from DTI, MTI and a novel, recently-proposed MWF-map processing and reconstruction algorithm were acquired from 54 healthy subjects (aged 18–79 years) and region-based multivariate regression analysis was performed. MWFs significantly decreased with age in most WM regions (except corticospinal tract) and changes of MWFs were associated with changes of radial diffusivity, indicating either substantial alterations or preservation of myelin content in these regions. Decreases of fractional anisotropy and magnetization transfer ratio were associated with lower MWFs in commissural fiber tracts only. Mean diffusivity had no regional effects on MWF. We conclude that MWF estimates are sensitive for the assessment of age-related myelin alterations in the cerebral WM of normal-aging brains.

Objective: Nucleophosmin-1 (NPM1) mutations have prognostic importance in acute myeloid leukemia (AML) patients with intermediate-risk karyotype at diagnosis. Approximately 30% of newly diagnosed cytogenetically normal AML (CN-AML) patients harbor the NPM1 mutation in India. In this study we compared the efficiency of three molecular techniques in detecting NPM1 mutation in peripheral blood and bone marrow samples. Materials and Methods: In a single-center cohort we analyzed 165 CN-AML bone marrow/peripheral blood samples for NPM1 mutation analysis. About 30% of the CN-AML samples revealed NPM1 mutations. For the detection, three methods were compared: Sanger sequencing, pyrosequencing, and real-time polymerase chain reaction (PCR). Results: NPM1 exon 12 mutations were observed in 52 (31.51%) of all CN-AML cases. The sensitivity of Sanger sequencing, pyrosequencing, and real-time PCR was 80%, 90%, and 95%, whereas specificity was 95%, 100%, and 100%, respectively. The minimum limit of mutation detection was 20%-30% for Sanger sequencing, 1%-5% for pyrosequencing, and 0.1%-1% for real-time PCR. Conclusion: The sequencing method, which is the reference method, has the lowest sensitivity and is sometimes difficult to interpret. Realtime PCR is a highly sensitive method for mutation detection but is limited for specific mutation types. In our study, pyrosequencing emerged as the most suitable technique for the detection of NPM1 mutations on the basis of its easy interpretation and less timeconsuming processes than Sanger sequencing.

Background: We share our experience of using droplet digital polymerase chain reaction (DdPCR) in liquid biopsy specimens for detecting primary and secondary epidermal growth factor receptor (EGFR) mutations among patients with nonsmall-cell lung cancer who had tissue biopsy initially analyzed for del19, L858R and T790M. Materials and Methods: Three groups of patients were chosen: Group 1: patients positive for EGFR mutation (del 19 or L858R) by conventional tissue biopsy that were treatment naïve, Group 2: patients positive for EGFR mutation (del 19 or L858R) by conventional tissue biopsy with acquired resistance to tyrosine kinase inhibitor (TKI) therapy, documented by radiology, and Group 3: no known EGFR mutation detected on primary tissue biopsy and treatment naive. Results: One hundred and thirty-three patients were included in the study. Group 1 had 40 cases, of which 21 (52.5%) and 19 (47.5%) were positive for del19 and L858R mutations, respectively, by tissue biopsy. DdPCR detected primary mutation in all but 5 cases. DdPCR additionally found four patients to have T790M mutation. Group 2 had 73 cases and DdPCR detected T790M mutation in 39 (53.4%) cases. Liquid biopsy also picked the original primary mutation in 56/73 cases. Secondary tissue biopsy for T790M mutation status was performed in 11 patients and while it detected mutation in 2 out of 11 cases, DdPCR detected the same in 7 cases, thus providing significantly superior yield (46% difference, McNemar's test, P value 0.063). Tissue biopsy additionally detected c-MET amplification in a patient who had T790M mutation on liquid biopsy. Group 3 had 20 patients and none were falsely positive for EGFR mutation on liquid biopsy. Overall, DdPCR had a Cohen's kappa of 0.82 (standard error 0.074, 95% CI 0.68–0.97) indicating “very good agreement” with conventional tissue biopsy. Conclusion: DdPCR demonstrated 87.5% sensitivity and 100% specificity in detecting primary EGFR mutations in patients who were treatment naïve with overall positive and negative predictive value of 100% and 80%, respectively. DdPCR demonstrated T790M mutation postprogression on TKI therapy in 53.4% patients.

Background: The frequency of ROS1 rearrangement in non-small cell lung cancers has been reported from 1.6% to 2.3%. Materials and Methods: We examined 105 lung adenocarcinoma patients for ROS1 rearrangement which were negative for EGFR and anaplastic lymphoma kinase. Clinical characteristics of ROS1 rearranged patients and their responses to crizotinib therapy were studied. Results: Of the 105 patients, three cases were positive for ROS1 rearrangement by fluorescence in situ hybridization analysis. All of them showed heterogeneous pattern. All the 3 ROS1-positive patients were females in their forties and started on crizotinib. All of them responded to treatment. One of them developed resistance after 3 months. Another one showed marked systemic response but central nervous system lesions progressed. The third case is doing well till date with inactive lesions on positron emission tomography scan. Conclusions: The frequency of ROS1 rearrangement is low in non-small cell lung carcinoma, but their diagnosis offers patients an opportunity to receive highly effective targeted therapies.

Aim: The present study was conducted to evaluate the antidiarrheal effect of ethanolic extract of Holarrhena antidysenterica (Family - Apocynaceae) seeds against induced diarrhea in Wistar albino rats. Materials and Methods: The extract was evaluated for castor oil and Escherichia coli induced diarrhea. Extract was given at 100, 200, 400 mg/kg body wt. orally in both protocols. Standard antidiarrheal Loperamide was used at 5 mg/kg body wt. orally in castor oil induced protocol, while standard antibiotic Gentamicin at 8 mg/kg body wt. intraperitoneally was used in E. coli induced diarrhea. In castor oil induced protocol, the percentage inhibition of defecation was calculated for each group, whereas in E. coli induced protocol, change in fecal consistency, and body weight was recorded for each individual rat for 3 days. Results: The severity of castor oil induced diarrhea was reduced significantly (p

Background: The herbal formulation consisting of Andrographis paniculata Nees., Cassia fistula L., Foeniculum vulgare Mill. and Cuminum cyminum L. is widely used by the local traditional practitioners in rural Northern Karnataka for spasmodic abdominal pain. Objective: The present study was undertaken to evaluate safety and spasmolytic effect of poly-herbal formulation. Materials and Methods: Acute toxicity studies were carried out in Swiss mice, as per the Organization for Economic Co-operation and Development (OECD) guidelines. The spasmolytic activity of the formulation was studied in isolated guinea pig ileum model using histamine and acetylcholine as agonists. The data were analyzed by one-way ANOVA, followed by Dunnetts post-hoc test and P ≤ 0.05 was considered as significant. Results: The formulation did not show any adverse toxic effects and found to be safe. It also showed significant (P < 0.05) relaxation in different agonist like histamine and acetylcholine-induced contractions in guinea pig ileum. Conclusions: Antispasmodic activity of the herbal formulation can be attributed to its atropine-like activity. The present findings, therefore, support its utility in spasmodic abdominal pain.

Background:The pastes prepared from roots of Plumbago zeylanica Linn. and barks of Holoptelea integrifolia Roxb. are widely used by traditional healers for the treatment of arthritis in rural northern Karnataka. Objective: The present study was undertaken to scientifically evaluate the safety and efficacy of traditionally used formulations in experimental animals.Materials and Methods: The study, approved by IAEC was carried out in male Wistar rats and dermal toxicity in rabbits. Carrageenan model was used to assess effect on acute inflammation. Paw volume were measured at 1, 2, 4, and 6 th hour postchallenge. Chronic inflammation was developed by using Complete Freund′s Adjuvant (CFA). Paw volume, ankle joint circumference, and body weight were assessed on 1 st , 4 th , 8 th , 14 th , 17 th , and 21 st day. Paste was applied once every day to the inflamed area of the paw of respective groups of animals, continuously for 14 days. Statistics: The data were analyzed by one way analysis of variance followed by Dunnett′s post hoc test. P ≤ 0.05 was considered as significant. Results: The formulations did not show any dermal toxicity and found to be safe. Both the pastes significantly (P < 0.05) suppressed, carrageenan-induced paw edema at 6 th hour and Holoptelea integrifolia appears to be more effective than Plumbago zeylanica. Significant reduction was observed in paw volume, ankle joint circumference and animal body weight gained. Conclusions: The tested formulations (P. zeylanica root and H. integrifolia bark pastes) showed significant antiinflammatory activity. The present findings therefore support its utility in arthritic pain, inflammation and the claim of traditional practitioners.

Introduction: Glycine max L. with Drakshasava, widely used by traditional healers as a formulation for the treatment of peptic ulcer in rural northern Karnataka in India, appears to be effective as assessed by patients and in our previously published research work of traditionally used formulation. Aim: The present study was undertaken to evaluate the safety and efficacy of the overnight water soaked G. max grains. This is one of the components of traditional formulation. The study, approved by Institutional Animal Ethics Committee was carried out in male Wistar rats after assessing its toxicity in mice. Materials and Methods: Four groups of rats (n = 6 in each group) were treated with aspirin 200 mg/kg oral. In addition to aspirin control group received normal saline, standard group received 20 mg/kg omeprazole and 3 rd and 4 th group received G. max 250 and 500 mg/kg, respectively. All treatments were administered orally every 24 h for 7 days. After 24 hours fasting, on the 8 th day stomach contents were aspirated under anesthesia to estimate free and total acidity. Stomachs were opened along the greater curvature to calculate ulcer index and subjected to histopathology studies. Statistics: The results were analyzed by one-way analysis of variance followed-by Dunnett′s post hoc test. P ≤0.05 was considered as significant. Results: The severity of aspirin induced ulceration was found significantly (P < 0.05) decreased in test groups compared with the control group. Free and total acidity was significantly reduced in 500 mg/kg treated group, compared with the control group and was inferior to omeprazole treated group. Conclusion: The grain of G. max was found to be effective against aspirin induced ulcers.

Introduction: Mutation detection from Formalin Fixed ParaffinEmbedding (FFPE) tissue in molecular lab became a necessary tool for defining potential targeted drug. Accurate quantification of DNA extracted from FFPE tissue is necessary for downstream applications like Polymerase Chain Reaction (PCR), sequencing etc. Aim: To check and define which method for FFPE DNA quantification is suitable for downstream processes. Materials and Methods: In this experimental experience study Biorad Smartspec Plus spectrophotomery, Qubit Fluorometer, and Qiagen Rotorgene qPCR was used to compare 20 FFPE DNA quantification in Rajiv Gandhi Cancer Institute and Research Centre, in 2015 and quantified amount of DNA used for PCR reaction. Results: The average concentration of DNA extracted from FFPE tissue measured using the spectrophotometer was much higher than the concentration measured using the Qubit Fluorometer and qPCR. Conclusion: Results varied depending upon the technique used. A fluorometric analysis may be more suitable for quantification of DNA samples extracted from FFPE tissue compared with spectrophotometric analysis. But qPCR is the best technique because it details DNA quantity along with quality of amplifiable DNA from FFPE tissue.

PurposeTo assess neuroprotection and remyelination in Multiple Sclerosis (MS), we applied a more robust myelin water imaging (MWI) processing technique, including spatial priors into image reconstruction, which allows for lower SNR, less averages and shorter acquisition times. We sought to evaluate this technique in MS-patients and healthy controls (HC).Materials and methodsSeventeen MS-patients and 14 age-matched HCs received a 3T Magnetic Resonance Imaging (MRI) examination including MWI (8 slices, 12 minutes acquisition time), T2w and T1mprage pre and post gadolinium (GD) administration. Black holes (BH), contrast enhancing lesions (CEL) and T2 lesions were marked and registered to MWI. Additionally, regions of interest (ROI) were defined in the frontal, parietal and occipital normal appearing white matter (NAWM)/white matter (WM), the corticospinal tract (CST), the splenium (SCC) and genu (GCC) of the corpus callosum in patients and HCs. Mean values of myelin water fraction (MWF) were determined for each ROI.ResultsSignificant differences (p≤0.05) of the MWF were found in all three different MS-lesion types (BH, CEL, T2 lesions), compared to the WM of HCs. The mean MWF values among the different lesion types were significantly differing from each other. Comparing MS-patients vs. HCs, we found a significant (p≤0.05) difference of the MWF in all measured ROIs except of GCC and SCC. The mean reduction of MWF in the NAWM of MS-patients compared to HCs was 37%. No age, sex, disability score and disease duration dependency was found for the NAWM MWF.ConclusionMWF measures were in line with previous studies and lesions were clearly visible in MWI. MWI allows for quantitative assessment of NAWM and lesions in MS, which could be used as an additional sensitive imaging endpoint for larger MS studies. Measurements of the MWF also differ between patients and healthy controls.

Background and Objectives: HER2 testing guideline of ASCO/CAP for interpretation and reporting has recently been revised. The study is aimed to measure the impact of 2013 CAP guideline on equivocal HER2 test outcome (immunohistochemistry [IHC] 2+) when tested by fluorescent in situ hybridization (FISH). The study also aims at finding the frequency of polysomy and monosomy of chromosome 17. Materials and Methods: Specimens were collected in Rajiv Gandhi Cancer Institute and Research Centre, New Delhi, India. IHC was performed in every case, and FISH was performed in IHC2+ cases. Results: In final analysis includes 557 subjects on the basis of CAP guideline 2007 and CAP guideline 2013. One hundred ninety-two subjects (34.4%) were HER2 amplified according to CAP scoring 2007, and 246 subjects (44%) according to 2013 CAP scoring. Conclusions: FISH results were evaluated (IHC2 + interpreted according to CAP 2007 guideline) with both 2007 and 2013 ASCO/CAP scoring criteria, we identified significantly more HER2 positive cases as compared to cases evaluated using the 2007 criteria (P < 0.05). We also found that in breast carcinoma, HER2 status in the presence of polysomy 17 may vary with the scoring criteria used. Evaluation of FISH result using 2013 ASCO/CAP criteria means that more patients with breast cancer may be appropriate for targeted treatment with trastuzumab, potentially improving their outcome.

The growth of pharma industries has slowed in recent years because of various reasons such as patent expiries, generic competition, drying pipelines, and increasingly stringent regulatory guidelines. Many blockbuster drugs will loose their exclusivity in next 5 years. Therefore, the current economic situation plus the huge generic competition shifted the focus of pharmaceutical companies from the essential medicines to the new business model - niche busters, also called orphan drugs. Orphan drugs may help pharma companies to reduce the impact of revenue loss caused by patent expiries of blockbuster drugs. The new business model of orphan drugs could offer an integrated healthcare solution that enables pharma companies to develop newer areas of therapeutics, diagnosis, treatment, monitoring, and patient support. Incentives for drug development provided by governments, as well as support from the FDA and EU Commission in special protocols, are a further boost for the companies developing orphan drugs. Although there may still be challenges ahead for the pharmaceutical industry, orphan drugs seem to offer the key to recovery and stability within the market. In our study, we have compared the policies and orphan drug incentives worldwide alongwith the challenges faced by the pharmaceutical companies. Recent developments are seen in orphan drug approval, the various drugs in orphan drug pipeline, and the future prospectives for orphan drugs and diseases.

OBJECTIVES: 1) To deduce T2, the inverse of the transverse relaxation rate (R2), in the hippocampus of healthy adults; 2) to investigate the brain iron deposition in Alzheimer's disease (AD) patients and age-matched healthy controls using T2-values. METHODS: T2-weighted data from the bilateral-hippocampi of ten AD patients and sixty healthy controls were collected at six echo time points using multi-slice multi-echo turbo spin echo (MSME-TSE) imaging on a 3.0 T MR-scanner, followed by the neuropsychological testing. The correlations between T2-values and Mini-Mental State Examination (MMSE) scores were investigated on group-wise basis (covariates in the group-wise analyses: gender, age, side and healthy/AD). RESULTS: There were no significant differences in hippocampal T2-values on intra-gender and inter-gender basis (P > 0.05). Hippocampal T2-values of both sides were similar (right: 85.2±2.4 milliseconds; left: 85.3±2.5 milliseconds). The bilateral hippocampal T2 values correlated moderately with age (right: r = -0.59; left: -0.58; P < 0.001). The AD-group had significantly lower T2-values in the hippocampus when compared to normal controls (P < 0.001) and such low T2-values had a strong positive correlation with the MMSE score (R (2) = 0.97; P < 0.05). CONCLUSION: Patients with AD showed significantly lower T2 values, which can be attributed to the increased iron depositions in the hippocampus. A positive correlation between T2-values and cognition scores suggests that quantitative T2 can be used in the early diagnosis of AD and in the monitoring of the treatment response.