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1. Prospects for Fundamental Physics with LISA

Author

Barausse, Enrico, Berti, Emanuele, Hertog, Thomas, Hughes, Scott A., Jetzer, Philippe, Pani, Paolo, Sotiriou, Thomas P., Tamanini, Nicola, Witek, Helvi, Yagi, Kent, Yunes, Nicolas, Abdelsalhin, T., Achucarro, A., Aelst, K. V., Afshordi, N., Akcay, S., Annulli, L., Arun, K. G., Ayuso, I., Baibhav, V., Baker, T., Bantilan, H., Barreiro, T., Barrera-Hinojosa, C., Bartolo, N., Baumann, D., Belgacem, E., Bellini, E., Bellomo, N., Ben-Dayan, I., Bena, I., Benkel, R., Bergshoefs, E., Bernard, L., Bernuzzi, S., Bertacca, D., Besancon, M., Beutler, F., Beyer, F., Bhagwat, S., Bicak, J., Biondini, S., Bize, S., Blas, D., Boehmer, C., Boller, K., Bonga, B., Bonvin, C., Bosso, P., Bozzola, G., Brax, P., Breitbach, M., Brito, R., Bruni, M., Brügmann, B., Bulten, H., Buonanno, A., Burke, A. O., Burko, L. M., Burrage, C., Cabral, F., Calcagni, G., Caprini, C., Cárdenas-Avendaño, A., Celoria, M., Chatziioannou, K., Chernoff, D., Clough, K., Coates, A., Comelli, D., Compère, G., Croon, D., Cruces, D., Cusin, G., Dalang, C., Danielsson, U., Das, S., Datta, S., de Boer, J., De Luca, V., De Rham, C., Desjacques, V., Destounis, K., Di Filippo, F., Dima, A., Dimastrogiovanni, E., Dolan, S., Doneva, D., Duque, F., Durrer, R., East, W., Easther, R., Elley, M., Ellis, J. R., Emparan, R., Ezquiaga, J. M., Fairbairn, M., Fairhurst, S., Farmer, H. F., Fasiello, M. R., Ferrari, V., Ferreira, P. G., Ficarra, G., Figueras, P., Fisenko, S., Foffa, S., Franchini, N., Franciolini, G., Fransen, K., Frauendiener, J., Frusciante, N., Fujita, R., Gair, J., Ganz, A., Garcia, P., Garcia-Bellido, J., Garriga, J., Geiger, R., Geng, C., Gergely, L. Á., Germani, C., Gerosa, D., Giddings, S. B., Gourgoulhon, E., Grandclement, P., Graziani, L., Gualtieri, L., Haggard, D., Haino, S., Halburd, R., Han, W. -B., Hawken, A. J., Hees, A., Heng, I. S., Hennig, J., Herdeiro, C., Hervik, S., Holten, J. v., Hoyle, C. J. D., Hu, Y., Hull, M., Ikeda, T., Isi, M., Jenkins, A., Julié, F., Kajfasz, E., Kalaghatgi, C., Kaloper, N., Kamionkowski, M., Karas, V., Kastha, S., Keresztes, Z., Kidder, L., Kimpson, T., Klein, A., Klioner, S., Kokkotas, K., Kolesova, H., Kolkowitz, S., Kopp, J., Koyama, K., Krishnendu, N. V., Kroon, J. A. V., Kunz, M., Lahav, O., Landragin, A., Lang, R. N., Poncin-Lafitte, C. Le, Lemos, J., Li, B., Liberati, S., Liguori, M., Lin, F., Liu, G., Lobo, F. S. N., Loll, R., Lombriser, L., Lovelace, G., Macedo, R. P., Madge, E., Maggio, E., Maggiore, M., Marassi, S., Marcoccia, P., Markakis, C., Martens, W., Martinovic, K., Martins, C. J. A. P., Maselli, A., Mastrogiovanni, S., Matarrese, S., Matas, A., Mavromatos, N. E., Mazumdar, A., Meerburg, P. D., Megias, E., Miller, J., Mimoso, J. P., Mittnacht, L., Montero, M. M., Moore, B., Martin-Moruno, P., Musco, I., Nakano, H., Nampalliwar, S., Nardini, G., Nielsen, A., Novák, J., Nunes, N. J., Okounkova, M., Oliveri, R., Oppizzi, F., Orlando, G., Oshita, N., Pappas, G., Paschalidis, V., Peiris, H., Peloso, M., Perkins, S., Pettorino, V., Pikovski, I., Pilo, L., Podolsky, J., Pontzen, A., Prabhat, S., Pratten, G., Prokopec, T., Prouza, M., Qi, H., Raccanelli, A., Rajantie, A., Randall, L., Raposo, G., Raymond, V., Renaux-Petel, S., Ricciardone, A., Riotto, A., Robson, T., Roest, D., Rollo, R., Rosofsky, S., Ruan, J. J., Rubiera-García, D., Ruiz, M., Rusu, M., Sabatie, F., Sago, N., Sakellariadou, M., Saltas, I. D., Sberna, L., Sathyaprakash, B., Scheel, M., Schmidt, P., Schutz, B., Schwaller, P., Shao, L., Shapiro, S. L., Shoemaker, D., Silva, A. d., Simpson, C., Sopuerta, C. F., Spallicci, A., Stefanek, B. A., Stein, L., Stergioulas, N., Stott, M., Sutton, P., Svarc, R., Tagoshi, H., Tahamtan, T., Takeda, H., Tanaka, T., Tantilian, G., Tasinato, G., Tattersall, O., Teukolsky, S., Tiec, A. L., Theureau, G., Trodden, M., Tolley, A., Toubiana, A., Traykova, D., Tsokaros, A., Unal, C., Unnikrishnan, C. S., Vagenas, E. C., Valageas, P., Vallisneri, M., Brand, J. Van den, Broeck, C. Van den, van de Meent, M., Vanhove, P., Varma, V., Veitch, J., Vercnocke, B., Verde, L., Vernieri, D., Vernizzi, F., Vicente, R., Vidotto, F., Visser, M., Vlah, Z., Vretinaris, S., Völkel, S., Wang, Q., Wang, Yu-Tong, Werner, M. C., Westernacher, J., Weygaert, R. v. d., Wiltshire, D., Wiseman, T., Wolf, P., Wu, K., Yamada, K., Yang, H., Yi, L., Yue, X., Yvon, D., Zilhão, M., Zimmerman, A., and Zumalacarregui, M.

Subjects
General Relativity and Quantum Cosmology
Abstract

In this paper, which is of programmatic rather than quantitative nature, we aim to further delineate and sharpen the future potential of the LISA mission in the area of fundamental physics. Given the very broad range of topics that might be relevant to LISA, we present here a sample of what we view as particularly promising directions, based in part on the current research interests of the LISA scientific community in the area of fundamental physics. We organize these directions through a "science-first" approach that allows us to classify how LISA data can inform theoretical physics in a variety of areas. For each of these theoretical physics classes, we identify the sources that are currently expected to provide the principal contribution to our knowledge, and the areas that need further development. The classification presented here should not be thought of as cast in stone, but rather as a fluid framework that is amenable to change with the flow of new insights in theoretical physics., Comment: 22 pages, 1 figure, to appear in General Relativity and Gravitation

Published
2020
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5. Synergistic Hypoxia and Apoptosis Conditioning Unleashes Superior Mesenchymal Stem Cells Efficacy in Acute Graft-versus-Host-Disease

Author

Mendiratta, Mohini, primary, Mendiratta, Meenakshi, additional, Ganguly, Shuvadeep Kumar, additional, Rai, Sandeep, additional, Gupta, Ritu, additional, Kumar, Lalit, additional, Bakhshi, Sameer, additional, Dadhwal, Vatsla, additional, Pushpam, Deepam, additional, Malik, Prabhat S, additional, Pramanik, Raja, additional, Aggarwal, Mukul, additional, Gupta, Aditya Kumar, additional, Dhawan, Rishi, additional, Seth, Tulika, additional, Mahapatra, Manoranjan, additional, Nayak, Baibaswata, additional, Singh, Thoudam Debraj, additional, Singla, Sachin Kumar, additional, Singh, Mayank, additional, Prasad, Chandra Prakash, additional, Prakash, Hridayesh, additional, Mohanty, Sujata, additional, and Sahoo, Ranjit Kumar, additional

Published
2024
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7. Analysis of miR-375-3p, miR-197-3p, and miR-15a-5p Expression and Their Clinical Relevance as Biomarkers in Lung Cancer

Author

Sachin Kumar PhD, Jyoutishman Saikia MCh, Surender K. Sharawat PhD, Prabhat S. Malik DM, Sunil Kumar MS, and Anant Mohan PhD

Subjects
Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract

Background: MicroRNAs (miRNAs) play an important regulatory role and serve as biomarkers in various human cancers. However, their role in the prognosis and predicting response to therapy in Indian lung cancer patients is not fully explored. Methods: We collected surgically resected tumors and paired adjacent normal lung tissues from 29 early-stage and tissue biopsies from 103 locally advanced and metastatic lung cancer patients in this prospective study. We quantified the expression levels of miR-375-3p, miR-197-3p, and miR-15a-5p using TaqMan Advanced miRNA Assays. We correlated miRNAs expression with response to therapy and survival outcomes. Results: The median age of lung cancer patients was 60 years. We found significant overexpression of miR-375-3p and miR-197-3p in the tumors compared to paired normal lung tissues. Higher expression of miR-375-3p was observed more frequently in responders compared to nonresponders. The expression of miR-375-3p and miR-197-3p was able to differentiate patients of lung adenocarcinoma from lung squamous cell carcinoma. We did not find any correlation between miRNAs expression and survival outcomes. Conclusion: Overexpression of miR-375-3p and miR-197-3p might contribute to lung carcinogenesis. The expression of miR-375-3p may assist in predicting therapeutic response. More prospective studies are warranted to evaluate the potential of miR-375-3p as a predictive biomarker of response to therapy.

Published
2022
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8. Stimulus-specific hypothalamic encoding of a persistent defensive state

Author

Kennedy, Ann, Kunwar, Prabhat S., Li, Ling-yun, Stagkourakis, Stefanos, Wagenaar, Daniel A., and Anderson, David J.

Subjects
Alarm reaction -- Analysis, Stimuli (Psychology) -- Physiological aspects, Hypothalamic hormones -- Control, Encoding (Memory) -- Psychological aspects, Environmental issues, Science and technology, Zoology and wildlife conservation
Abstract

Persistent neural activity in cortical, hippocampal, and motor networks has been described as mediating working memory for transiently encountered stimuli.sup.1,2. Internal emotional states, such as fear, also persist following exposure to an inciting stimulus.sup.3, but it is unclear whether slow neural dynamics are involved in this process. Neurons in the dorsomedial and central subdivisions of the ventromedial hypothalamus (VMHdm/c) that express the nuclear receptor protein NR5A1 (also known as SF1) are necessary for defensive responses to predators in mice.sup.4-7. Optogenetic activation of these neurons, referred to here as VMHdm.sup.SF1 neurons, elicits defensive behaviours that outlast stimulation.sup.5,8, which suggests the induction of a persistent internal state of fear or anxiety. Here we show that in response to naturalistic threatening stimuli, VMHdm.sup.SF1 neurons in mice exhibit activity that lasts for many tens of seconds. This persistent activity was correlated with, and required for, persistent defensive behaviour in an open-field assay, and depended on neurotransmitter release from VMHdm.sup.SF1 neurons. Stimulation and calcium imaging in acute slices showed that there is local excitatory connectivity between VMHdm.sup.SF1 neurons. Microendoscopic calcium imaging of VMHdm.sup.SF1 neurons revealed that persistent activity at the population level reflects heterogeneous dynamics among individual cells. Unexpectedly, distinct but overlapping VMHdm.sup.SF1 subpopulations were persistently activated by different modalities of threatening stimulus. Computational modelling suggests that neither recurrent excitation nor slow-acting neuromodulators alone can account for persistent activity that maintains stimulus identity. Our results show that stimulus-specific slow neural dynamics in the hypothalamus, on a time scale orders of magnitude longer than that of working memory in the cortex.sup.9,10, contribute to a persistent emotional state. Persistent neural activity in the mouse hypothalamus encodes aversive emotional states related to specific threatening stimuli., Author(s): Ann Kennedy [sup.1] , Prabhat S. Kunwar [sup.1] [sup.3] , Ling-yun Li [sup.1] , Stefanos Stagkourakis [sup.1] , Daniel A. Wagenaar [sup.1] , David J. Anderson [sup.1] [sup.2] Author [...]

Published
2020
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9. Discordance in Biomarker Expression in Breast Cancer After Metastasis: Single Center Experience in India

Author

Ajay Gogia, S. V. Suryanarayana Deo, Dayanand Sharma, Rakesh K. Phulia, Sanjay Thulkar, Prabhat S. Malik, and Sandeep Mathur

Subjects
Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract

PURPOSE: Biomarker—estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2/neu) —discordance plays an essential role in the management and prognosis of patients with metastatic breast cancer. Rates of discordance have been previously reported around 12% to 35%, 30% to 50%, and 5% to 15%, respectively, in Western literature. Data are sparse regarding the same from developing countries, such as India. METHODS: We performed an ambispective review of paired biomarker status in patients with breast cancer—stage I, II, and III as per American Joint Committee on Cancer, 7th edition—who developed metastasis at recurrence (N = 103 patients). Biomarker status and clinical and radiologic parameters were documented at baseline and subsequent follow-up. RESULTS: Discordance was present in 21.3% for ER, 29.1% for PR, and 15.5% for HER2/neu receptor. In our cohort, 7.8% had positive to negative ER and 13.6% negative to positive. Whereas 21.4% had positive to negative PR, 7.8% had negative to positive PR. Approximately 6.8% had positive to negative HER2/neu receptor and 8.7% negative to positive. In our cohort, 41 patients (40%) had single-site metastasis—bone, 15.5%; lung, 11.7%; nonregional lymph node, 7.8%; liver, 3.9%; and brain, 0.97%. More than one site of metastasis was present in 62 patients (60%). The most common sites of metastasis were visceral—lung and liver—followed by bone, nonregional lymph node, skin, and brain. CONCLUSION: The current study demonstrated that metastatic disease evolution in breast cancer is characterized by change in the tumor biology, which leads to discordance in receptor status. Repeat biomarker studies at metastatic recurrence is warranted, especially if treatment plans include hormone and targeted therapy.

Published
2019
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10. Clinicopathologic Characteristics and Treatment Outcomes of Patients With Up-Front Metastatic Breast Cancer: Single-Center Experience in India

Author

Ajay Gogia, Suryanarayana Vishnu S. Deo, Dayanand Sharma, Sanjay Thulkar, Rakesh Kumar, Prabhat S. Malik, and Sandeep Mathur

Subjects
Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract

PURPOSE: Approximately 5% to 10% of patients with breast cancer present with up-front metastasis and carry a poor prognosis (5-year survival rates of approximately 20%). To date, little is known about the long-term outcome of patients with metastatic breast cancer from developing nations. MATERIALS AND METHODS: We performed an ambispective review of approximately 1,800 patients who were registered in breast cancer clinics between January 2012 and August 2018. Approximately 410 (22.8%) patients presented with up-front metastasis. Out of 410, 375 were considered for additional analysis. Clinical, pathologic, and radiologic details were obtained from the medical records. RESULTS: Median age of presentation was 49 years (range, 22 to 80 years), and median duration of symptoms was 6 months (interquartile range, 3-12 months). Baseline receptor status suggested that 234 patients (62.4%) were hormone receptor (HR) positive, 145 (38.6%) were human epidermal growth factor receptor positive, and 69 (18.6%) had triple-negative breast cancer. Various sites of metastasis were: visceral 219 (58.4%), bone only 100 (26.7%), nonregional lymph node metastasis 21 (5.6%), brain 10 (2.7%), and others 25 (5.8%). Approximately 309 patients (82.4%) received up-front chemotherapy, 192 HR-positive patients (82.1%) received endocrine therapy, and 78 human epidermal growth factor receptor–positive patients (53.8%) received targeted agents. Median progression-free survival was 14.2 months (95% CI, 12.7 to 16.8 months), and median overall survival (OS) was 31.7 months (95% CI, 25.8 to 38.2 months) for the cohort. Median time of follow-up was 22.2 months. On multivariable Cox regression analysis, HR-positive disease, good performance status (0 or 1), and oligometastasis were associated with better OS, whereas triple-negative breast cancer and liver and brain metastasis were associated with inferior OS. CONCLUSION: This is the first comprehensive study, to our knowledge, of metastatic breast cancer from India. HR-positive status, oligometastasis, and good performance status were associated with better outcomes.

Published
2019
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11. Genetic dissection of an amygdala microcircuit that gates conditioned fear

Author

Haubensak, Wulf, Kunwar, Prabhat S, Cai, Haijiang, Ciocchi, Stephane, Wall, Nicholas R, Ponnusamy, Ravikumar, Biag, Jonathan, Dong, Hong-Wei, Deisseroth, Karl, Callaway, Edward M, Fanselow, Michael S, Lüthi, Andreas, and Anderson, David J

Subjects
Biomedical and Clinical Sciences, Neurosciences, 1.1 Normal biological development and functioning, Underpinning research, Neurological, Amygdala, Animals, Axonal Transport, Cells, Cultured, Conditioning, Classical, Fear, Female, Freezing Reaction, Cataleptic, Genetic Techniques, Humans, Male, Mice, Mice, Transgenic, Neural Inhibition, Neural Pathways, Neurons, Protein Kinase C-delta, Synapses, gamma-Aminobutyric Acid, General Science & Technology
Abstract

The role of different amygdala nuclei (neuroanatomical subdivisions) in processing Pavlovian conditioned fear has been studied extensively, but the function of the heterogeneous neuronal subtypes within these nuclei remains poorly understood. Here we use molecular genetic approaches to map the functional connectivity of a subpopulation of GABA-containing neurons, located in the lateral subdivision of the central amygdala (CEl), which express protein kinase C-δ (PKC-δ). Channelrhodopsin-2-assisted circuit mapping in amygdala slices and cell-specific viral tracing indicate that PKC-δ(+) neurons inhibit output neurons in the medial central amygdala (CEm), and also make reciprocal inhibitory synapses with PKC-δ(-) neurons in CEl. Electrical silencing of PKC-δ(+) neurons in vivo suggests that they correspond to physiologically identified units that are inhibited by the conditioned stimulus, called CEl(off) units. This correspondence, together with behavioural data, defines an inhibitory microcircuit in CEl that gates CEm output to control the level of conditioned freezing.

Published
2010

12. Multiple Myeloma: Impact of Time to Transplant on the Outcome

Author

Lalit Kumar, Mohammad Mir Hussain, Rajegowda Chethan, Ranjit Kumar Sahoo, Prabhat S. Malik, Om Dutt Sharma, Anisha Mathew, Ankit Jha, Ritu Gupta, Atul Sharma, Ahitagni Biswas, Rakesh Kumar, Sanjay Thulkar, Soumyaranjan Malik, and Ashish Dutt

Subjects
Adult, Male, Cancer Research, Hematopoietic Stem Cell Transplantation, Hematology, Middle Aged, Transplantation, Autologous, Disease-Free Survival, Young Adult, Treatment Outcome, Oncology, Antineoplastic Combined Chemotherapy Protocols, Humans, Female, Multiple Myeloma, Melphalan, Aged, Retrospective Studies
Abstract

Autologous stem cell transplant (ASCT) is a standard therapy for transplant eligible patients of multiple myeloma (MM). To evaluate impact of time to transplant on subsequent outcomes, we analyzed data on consecutive MM patients who received novel agents-based induction prior to transplant.Between 2006 and 2019, 363 MM patients underwent ASCT. Patients' median age was 52 years, ranging from 20 to 72 years, 233 (64.2%) were males. Median interval from diagnosis to transplant was 11.5 months (range, 4-67.5); 201 (55.4%) patients underwent ASCT within 12 months (early) and 162 (44.6%) beyond 12 months since diagnosis (delayed ASCT). Primary objective was progression-free survival. Secondary objectives were-response rate to transplant, overall survival (OS), and transplant-related mortality (TRM).Post-ASCT complete response (CR) (77.1% vs. 64.8%; P.025) and CR+ very good partial response rate (89% vs. 81.5%; P.03) was higher for early ASCT cohort. Engraftment characteristics, regimen-related toxicities, and day +100 TRM (3.5% vs 3.7%; P = .564) were similar in 2 cohorts. Median OS for early versus late cohort from date of diagnosis is 127.0 (95% CI, 98.9-155.1) versus 104.5 months (95% CI, 79.3-129.6; P = .356) and from date of transplant is 119.0 (95% CI, 93.4-144.6) versus 89.5 months (95% CI, 57.4-121.6), P.02. Median PFS is better for early transplant cohort; 69.5 (95% CI, 56.7-82.3) versus 50.0 months (95% CI, 35.6-64.4), P.05, respectively.Early transplant for myeloma is associated with higher response rate and better progression-free survival.

Published
2022

13. Tre1, a G protein-coupled receptor, directs transepithelial migration of Drosophila germ cells.

Author

Kunwar, Prabhat S, Starz-Gaiano, Michelle, Bainton, Roland J, Heberlein, Ulrike, and Lehmann, Ruth

Subjects
Germ Cells, Epithelium, Leukocytes, Embryo, Nonmammalian, Animals, Humans, Drosophila melanogaster, Inflammation, rho GTP-Binding Proteins, Drosophila Proteins, Receptors, G-Protein-Coupled, Receptors, Chemokine, RNA, Cell Transplantation, Immunohistochemistry, In Situ Hybridization, Cloning, Molecular, Crosses, Genetic, Evolution, Molecular, Phylogeny, Signal Transduction, Cell Movement, Gene Expression Regulation, Phenotype, Mutation, Models, Biological, Molecular Sequence Data, Female, Male, Embryo, Nonmammalian, Receptors, G-Protein-Coupled, Chemokine, Cloning, Molecular, Crosses, Genetic, Evolution, Models, Biological, Biological Sciences, Agricultural and Veterinary Sciences, Medical and Health Sciences, Developmental Biology
Abstract

In most organisms, germ cells are formed distant from the somatic part of the gonad and thus have to migrate along and through a variety of tissues to reach the gonad. Transepithelial migration through the posterior midgut (PMG) is the first active step during Drosophila germ cell migration. Here we report the identification of a novel G protein-coupled receptor (GPCR), Tre1, that is essential for this migration step. Maternal tre1 RNA is localized to germ cells, and tre1 is required cell autonomously in germ cells. In tre1 mutant embryos, most germ cells do not exit the PMG. The few germ cells that do leave the midgut early migrate normally to the gonad, suggesting that this gene is specifically required for transepithelial migration and that mutant germ cells are still able to recognize other guidance cues. Additionally, inhibiting small Rho GTPases in germ cells affects transepithelial migration, suggesting that Tre1 signals through Rho1. We propose that Tre1 acts in a manner similar to chemokine receptors required during transepithelial migration of leukocytes, implying an evolutionarily conserved mechanism of transepithelial migration. Recently, the chemokine receptor CXCR4 was shown to direct migration in vertebrate germ cells. Thus, germ cells may more generally use GPCR signaling to navigate the embryo toward their target.

Published
2003

14. Comprehensive Germline Genomic Profiling of Patients with Ovarian Cancer: A Cross-Sectional Study

Author

Raja Pramanik, Avinash Upadhyay, Sachin Khurana, Lalit Kumar, Prabhat S. Malik, Sunesh Kumar, M. D. Ray, S. V. S. Deo, Ritu Gupta, Deepshi Thakral, Sanjay Thulkar, and V. L. Ramprasad

Subjects
Oncology, Pediatrics, Perinatology and Child Health
Abstract

Introduction Ovarian cancer is the third most common cancer among Indian women. The data on the hereditary predisposition of these cancers and the clinical outcomes of those with pathogenic mutations is meager in India. Objective The aim of the current study was to analyze the germline-genetic profile, clinicopathological characteristics, and outcomes of patients with ovarian cancer who were referred for genetic counseling at our Institute. Materials and Methods It was a cross-sectional observational study. Patients with histological diagnosis of carcinoma ovary at our institute who were referred for genetic counseling from July 2017 to June 2020 were included in the study. All patients underwent pretest counseling. Most patients underwent multigene panel testing with reflex multiplication ligation-dependent probe amplification for large genomic rearrangements, while some received testing for BRCA1 and BRCA2 only. The variants were classified as pathogenic or benign based on American College of Medical Genetics (ACMG) guidelines. Data regarding the demographic profile, clinical characteristics, histopathological findings, family history, treatment received, and outcomes were extracted from the medical record system files. Results One hundred and one patients were referred to the genetic clinic and underwent genetic counseling. All patients were advised for genetic testing; however, only 72 (71%) underwent testing. A multigene panel testing was done in 51 (70%) patients, and only BRCA1 and BRCA2 genes were tested in 21 (30%). Among the 72 patients who underwent a genetic test, the median age was 47 years (range, 28–82). The most common histopathology was serous (90%), while 85% were diagnosed having stage 3 and 4 ovarian cancer. A pathogenic/likely pathogenic (P/LP) BRCA or non-BRCA mutation was detected in 32 (44%) patients. Six patients (8%) had a variant of unknown significance (VUS). Among P/LP mutations, 85% were in the BRCA gene (75% in BRCA1 and 10% in BRCA2), while 15% were in non-BRCA gene mutations (RAD51, PALB2, MER11, HMMR). Disease-free survival and overall survival were not different in mutation-positive and mutation-negative cohorts. Conclusions We report 44% P/LP mutations in this selected cohort of patients with carcinoma ovaries. BRCA mutations constituted 85% of all the mutations, while 15% of mutations were in non-BRCA genes.

Published
2022

15. Sixth Sense Jacket

Author

Pandey Prabhat S., Chakraborty Shreya S., Gaikwad Jay S., and Shah Divya K.

Subjects
Information technology, T58.5-58.64
Abstract

In a time when the entire world is going through a pandemic which can be curbed or substantially avoided and reduced by maintaining distance, it is crucial for every individual to follow the social distancing norms. However, it can be a challenging and daunting task to ensure safe distance all the time. Thus a Sixth Sense Jacket is a great way to keep the user mindful and alert of their surrounding without actually being alert all the time. It can not only alert the user but can also keep daily essentials such as keys and cards clean using dry sanitization. The jacket comes with a bunch of special features such as Pulse Oximeter which can be used to check vital health stats such as heart rate and blood saturation (SpO2) levels. The prime purpose of the Sixth Sense Jacket is to keep the user passively mindful of it's surrounding all the time and thus can be used in any field where it is crucial to stay alert in a given surrounding. The various domains this jacket can be used are women safety, battlefield and to add an extra sense to visually impaired people. The jacket can be a useful means to pre-empt any given danger that might befall the user and hence the name "Sixth Sense" Jacket.

Published
2021
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17. DeepMPS: Development and validation of a deep learning model for whole slide image base prognostic prediction of low grade Lung adenocarcinoma patients

Author

Akshay Jagajampi, Seema Khadirnaikar, Prabhat S Malik, Deepali Jain, MB Naveen, and Sudhanshu K Shukla

Abstract

Lung adenocarcinoma (LUAD) is one of the most common cancers, and patients’ prognostication is crucial for treatment decisions. Histopathological images are the most generally accessible clinical information, however they have not been employed in clinical settings for prognosis.In this study, we used WSIs and clinical data from TCGA (training and testing) and East Asian Cohort (EAS, Validation) to develop and validate DL-based prognosticator. To circumvent the need for manual ROI generation, WSIs from these patients were divided into smaller patches and scored. DeepMPS prediction model was built using the top scoring 226,383 patches. The DeepMPS model showed a C-index of 0.638 in the TCGA training cohort. The univariate and multivariate cox regression analysis identified DeepMPS as an independent predictor of survival (HR: 9.48, p-value: Author SummaryRight from the initial step of cancer diagnosis, histopathological images are the widely relied source of information for therapeutic decision making. Though these images carry a substantial amount of information, their use remains restricted to determining the grade of the tumor by pathologists. The advent of computational techniques has given rise to the ability to capture vital information besides the grade of the tumor, which humans might not be able to quantify visually. To this end, this work proposes a deep learning based model, Deep Multi-Modal Prognosis System (DeepMPS), to predict the prognosis of the patients based on the histopathological images to provide additional information to the pathologist which will aid in clinical decision making. DeepMPS predicts a risk score associated with each individual based on histopathological images and clinical factors. The risk score obtained from the proposed system is an independent predictor of survival. As the proposed system is independent of the manual region-of-interest (RoI) generation, it will ease the pathologist’s workload.

Published
2022

18. Autologous stem cell transplant for multiple myeloma: Impact of melphalan dose on the transplant outcome

Author

Lalit, Kumar, Ranjit Kumar, Sahoo, Sudhir, Kumar, Annie K, Baa, Ghazal, Tansir, Neha, Pathak, Prabhat S, Malik, Om Dutt, Sharma, Anisha, Mathew, Ankit, Jha, Ritu, Gupta, Atul, Sharma, Ahitagni, Biswas, Rakesh, Kumar, Sanjay, Thulkar, Soumyaranjan, Malik, and Ashish, Dutt

Subjects
Cancer Research, Oncology, Hematology
Abstract

We evaluated impact of melphalan dose on transplant outcomes for multiple myeloma. Between 1995 and 2019 459 consecutive patients received a transplant; 69(15%) received melphalan ≤150 mg/m2 (Mel 150 cohort) and 390 (85%) melphalan 200 mg/m2 (MEL 200 cohort). The primary outcome was overall survival (OS) from the date of transplant. Progression-free survival (PFS), engraftment, transplant response, and cumulative relapse at 2 years were secondary outcome measures. Patients in Mel 150 cohort had adverse clinical and laboratory parameters at base line. Transplant response was better for Mel 200 cohort (

Published
2022

21. Prospects for fundamental physics with LISA

Author

Barausse, E, Berti, E, Hertog, T, Hughes, S, Jetzer, P, Pani, P, Sotiriou, T, Tamanini, N, Witek, H, Yagi, K, Yunes, N, Abdelsalhin, T, Achucarro, A, van Aelst, K, Afshordi, N, Akcay, S, Annulli, L, Arun, K, Ayuso, I, Baibhav, V, Baker, T, Bantilan, H, Barreiro, T, Barrera-Hinojosa, C, Bartolo, N, Baumann, D, Belgacem, E, Bellini, E, Bellomo, N, Ben-Dayan, I, Bena, I, Benkel, R, Bergshoefs, E, Bernard, L, Bernuzzi, S, Bertacca, D, Besancon, M, Beutler, F, Beyer, F, Bhagwat, S, Bicak, J, Biondini, S, Bize, S, Blas, D, Boehmer, C, Boller, K, Bonga, B, Bonvin, C, Bosso, P, Bozzola, G, Brax, P, Breitbach, M, Brito, R, Bruni, M, Brügmann, B, Bulten, H, Buonanno, A, Burko, L, Burrage, C, Cabral, F, Calcagni, G, Caprini, C, Cárdenas-Avendaño, A, Celoria, M, Chatziioannou, K, Chernoff, D, Clough, K, Coates, A, Comelli, D, Compère, G, Croon, D, Cruces, D, Cusin, G, Dalang, C, Danielsson, U, Das, S, Datta, S, de Boer, J, De Luca, V, De Rham, C, Desjacques, V, Destounis, K, Filippo, F, Dima, A, Dimastrogiovanni, E, Dolan, S, Doneva, D, Duque, F, Durrer, R, East, W, Easther, R, Elley, M, Ellis, J, Emparan, R, Ezquiaga, J, Fairbairn, M, Fairhurst, S, Farmer, H, Fasiello, M, Ferrari, V, Ferreira, P, Ficarra, G, Figueras, P, Fisenko, S, Foffa, S, Franchini, N, Franciolini, G, Fransen, K, Frauendiener, J, Frusciante, N, Fujita, R, Gair, J, Ganz, A, Garcia, P, Garcia-Bellido, J, Garriga, J, Geiger, R, Geng, C, Gergely, L, Germani, C, Gerosa, D, Giddings, S, Gourgoulhon, E, Grandclement, P, Graziani, L, Gualtieri, L, Haggard, D, Haino, S, Halburd, R, Han, W, Hawken, A, Hees, A, Heng, I, Hennig, J, Herdeiro, C, Hervik, S, Holten, J, Hoyle, C, Hu, Y, Hull, M, Ikeda, T, Isi, M, Jenkins, A, Julié, F, Kajfasz, E, Kalaghatgi, C, Kaloper, N, Kamionkowski, M, Karas, V, Kastha, S, Keresztes, Z, Kidder, L, Kimpson, T, Klein, A, Klioner, S, Kokkotas, K, Kolesova, H, Kolkowitz, S, Kopp, J, Koyama, K, Krishnendu, N, Kroon, J, Kunz, M, Lahav, O, Landragin, A, Lang, R, Poncin-Lafitte, C, Lemos, J, Li, B, Liberati, S, Liguori, M, Lin, F, Liu, G, Lobo, F, Loll, R, Lombriser, L, Lovelace, G, Macedo, R, Madge, E, Maggio, E, Maggiore, M, Marassi, S, Marcoccia, P, Markakis, C, Martens, W, Martinovic, K, Martins, C, Maselli, A, Mastrogiovanni, S, Matarrese, S, Matas, A, Mavromatos, N, Mazumdar, A, Meerburg, P, Megias, E, Miller, J, Mimoso, J, Mittnacht, L, Montero, M, Moore, B, Martin-Moruno, P, Musco, I, Nakano, H, Nampalliwar, S, Nardini, G, Nielsen, A, Novák, J, Nunes, N, Okounkova, M, Oliveri, R, Oppizzi, F, Orlando, G, Oshita, N, Pappas, G, Paschalidis, V, Peiris, H, Peloso, M, Perkins, S, Pettorino, V, Pikovski, I, Pilo, L, Podolsky, J, Pontzen, A, Prabhat, S, Pratten, G, Prokopec, T, Prouza, M, Qi, H, Raccanelli, A, Rajantie, A, Randall, L, Raposo, G, Raymond, V, Renaux-Petel, S, Ricciardone, A, Riotto, A, Robson, T, Roest, D, Rollo, R, Rosofsky, S, Ruan, J, Rubiera-García, D, Ruiz, M, Rusu, M, Sabatie, F, Sago, N, Sakellariadou, M, Saltas, I, Sberna, L, Sathyaprakash, B, Scheel, M, Schmidt, P, Schutz, B, Schwaller, P, Shao, L, Shapiro, S, Shoemaker, D, Silva, A, Simpson, C, Sopuerta, C, Spallicci, A, Stefanek, B, Stein, L, Stergioulas, N, Stott, M, Sutton, P, Svarc, R, Tagoshi, H, Tahamtan, T, Takeda, H, Tanaka, T, Tantilian, G, Tasinato, G, Tattersall, O, Teukolsky, S, Tiec, A, Theureau, G, Trodden, M, Tolley, A, Toubiana, A, Traykova, D, Tsokaros, A, Unal, C, Unnikrishnan, C, Vagenas, E, Valageas, P, Vallisneri, M, Brand, J, Broeck, C, de Meent, M, Vanhove, P, Varma, V, Veitch, J, Vercnocke, B, Verde, L, Vernieri, D, Vernizzi, F, Vicente, R, Vidotto, F, Visser, M, Vlah, Z, Vretinaris, S, Völkel, S, Wang, Q, Wang, Y, Werner, M, Westernacher, J, Weygaert, R, Wiltshire, D, Wiseman, T, Wolf, P, Wu, K, Yamada, K, Yang, H, Yi, L, Yue, X, Yvon, D, Zilhão, M, Zimmerman, A, Zumalacarregui, M, Barausse, Enrico, Berti, Emanuele, Hertog, Thomas, Hughes, Scott A., Jetzer, Philippe, Pani, Paolo, Sotiriou, Thomas P., Tamanini, Nicola, Witek, Helvi, Yagi, Kent, Yunes, Nicolás, Abdelsalhin, T., Achucarro, A., van Aelst, K., Afshordi, N., Akcay, S., Annulli, L., Arun, K. G., Ayuso, I., Baibhav, V., Baker, T., Bantilan, H., Barreiro, T., Barrera-Hinojosa, C., Bartolo, N., Baumann, D., Belgacem, E., Bellini, E., Bellomo, N., Ben-Dayan, I., Bena, I., Benkel, R., Bergshoefs, E., Bernard, L., Bernuzzi, S., Bertacca, D., Besancon, M., Beutler, F., Beyer, F., Bhagwat, S., Bicak, J., Biondini, S., Bize, S., Blas, D., Boehmer, C., Boller, K., Bonga, B., Bonvin, C., Bosso, P., Bozzola, G., Brax, P., Breitbach, M., Brito, R., Bruni, M., Brügmann, B., Bulten, H., Buonanno, A., Burko, L. M., Burrage, C., Cabral, F., Calcagni, G., Caprini, C., Cárdenas-Avendaño, A., Celoria, M., Chatziioannou, K., Chernoff, D., Clough, K., Coates, A., Comelli, D., Compère, G., Croon, D., Cruces, D., Cusin, G., Dalang, C., Danielsson, U., Das, S., Datta, S., de Boer, J., De Luca, V., De Rham, C., Desjacques, V., Destounis, K., Filippo, F. Di, Dima, A., Dimastrogiovanni, E., Dolan, S., Doneva, D., Duque, F., Durrer, R., East, W., Easther, R., Elley, M., Ellis, J. R., Emparan, R., Ezquiaga, J. M., Fairbairn, M., Fairhurst, S., Farmer, H. F., Fasiello, M. R., Ferrari, V., Ferreira, P. G., Ficarra, G., Figueras, P., Fisenko, S., Foffa, S., Franchini, N., Franciolini, G., Fransen, K., Frauendiener, J., Frusciante, N., Fujita, R., Gair, J., Ganz, A., Garcia, P., Garcia-Bellido, J., Garriga, J., Geiger, R., Geng, C., Gergely, L. Á., Germani, C., Gerosa, D., Giddings, S. B., Gourgoulhon, E., Grandclement, P., Graziani, L., Gualtieri, L., Haggard, D., Haino, S., Halburd, R., Han, W. -B., Hawken, A. J., Hees, A., Heng, I. S., Hennig, J., Herdeiro, C., Hervik, S., Holten, J. v., Hoyle, C. J. D., Hu, Y., Hull, M., Ikeda, T., Isi, M., Jenkins, A., Julié, F., Kajfasz, E., Kalaghatgi, C., Kaloper, N., Kamionkowski, M., Karas, V., Kastha, S., Keresztes, Z., Kidder, L., Kimpson, T., Klein, A., Klioner, S., Kokkotas, K., Kolesova, H., Kolkowitz, S., Kopp, J., Koyama, K., Krishnendu, N. V., Kroon, J. A. V., Kunz, M., Lahav, O., Landragin, A., Lang, R. N., Poncin-Lafitte, C. Le, Lemos, J., Li, B., Liberati, S., Liguori, M., Lin, F., Liu, G., Lobo, F. S. N., Loll, R., Lombriser, L., Lovelace, G., Macedo, R. P., Madge, E., Maggio, E., Maggiore, M., Marassi, S., Marcoccia, P., Markakis, C., Martens, W., Martinovic, K., Martins, C. J. A. P., Maselli, A., Mastrogiovanni, S., Matarrese, S., Matas, A., Mavromatos, N. E., Mazumdar, A., Meerburg, P. D., Megias, E., Miller, J., Mimoso, J. P., Mittnacht, L., Montero, M. M., Moore, B., Martin-Moruno, P., Musco, I., Nakano, H., Nampalliwar, S., Nardini, G., Nielsen, A., Novák, J., Nunes, N. J., Okounkova, M., Oliveri, R., Oppizzi, F., Orlando, G., Oshita, N., Pappas, G., Paschalidis, V., Peiris, H., Peloso, M., Perkins, S., Pettorino, V., Pikovski, I., Pilo, L., Podolsky, J., Pontzen, A., Prabhat, S., Pratten, G., Prokopec, T., Prouza, M., Qi, H., Raccanelli, A., Rajantie, A., Randall, L., Raposo, G., Raymond, V., Renaux-Petel, S., Ricciardone, A., Riotto, A., Robson, T., Roest, D., Rollo, R., Rosofsky, S., Ruan, J. J., Rubiera-García, D., Ruiz, M., Rusu, M., Sabatie, F., Sago, N., Sakellariadou, M., Saltas, I. D., Sberna, L., Sathyaprakash, B., Scheel, M., Schmidt, P., Schutz, B., Schwaller, P., Shao, L., Shapiro, S. L., Shoemaker, D., Silva, A. d., Simpson, C., Sopuerta, C. F., Spallicci, A., Stefanek, B. A., Stein, L., Stergioulas, N., Stott, M., Sutton, P., Svarc, R., Tagoshi, H., Tahamtan, T., Takeda, H., Tanaka, T., Tantilian, G., Tasinato, G., Tattersall, O., Teukolsky, S., Tiec, A. L., Theureau, G., Trodden, M., Tolley, A., Toubiana, A., Traykova, D., Tsokaros, A., Unal, C., Unnikrishnan, C. S., Vagenas, E. C., Valageas, P., Vallisneri, M., Brand, J. Van den, Broeck, C. Van den, de Meent, M. van, Vanhove, P., Varma, V., Veitch, J., Vercnocke, B., Verde, L., Vernieri, D., Vernizzi, F., Vicente, R., Vidotto, F., Visser, M., Vlah, Z., Vretinaris, S., Völkel, S., Wang, Q., Wang, Yu-Tong, Werner, M. C., Westernacher, J., Weygaert, R. v. d., Wiltshire, D., Wiseman, T., Wolf, P., Wu, K., Yamada, K., Yang, H., Yi, L., Yue, X., Yvon, D., Zilhão, M., Zimmerman, A., Zumalacarregui, M., Barausse, E, Berti, E, Hertog, T, Hughes, S, Jetzer, P, Pani, P, Sotiriou, T, Tamanini, N, Witek, H, Yagi, K, Yunes, N, Abdelsalhin, T, Achucarro, A, van Aelst, K, Afshordi, N, Akcay, S, Annulli, L, Arun, K, Ayuso, I, Baibhav, V, Baker, T, Bantilan, H, Barreiro, T, Barrera-Hinojosa, C, Bartolo, N, Baumann, D, Belgacem, E, Bellini, E, Bellomo, N, Ben-Dayan, I, Bena, I, Benkel, R, Bergshoefs, E, Bernard, L, Bernuzzi, S, Bertacca, D, Besancon, M, Beutler, F, Beyer, F, Bhagwat, S, Bicak, J, Biondini, S, Bize, S, Blas, D, Boehmer, C, Boller, K, Bonga, B, Bonvin, C, Bosso, P, Bozzola, G, Brax, P, Breitbach, M, Brito, R, Bruni, M, Brügmann, B, Bulten, H, Buonanno, A, Burko, L, Burrage, C, Cabral, F, Calcagni, G, Caprini, C, Cárdenas-Avendaño, A, Celoria, M, Chatziioannou, K, Chernoff, D, Clough, K, Coates, A, Comelli, D, Compère, G, Croon, D, Cruces, D, Cusin, G, Dalang, C, Danielsson, U, Das, S, Datta, S, de Boer, J, De Luca, V, De Rham, C, Desjacques, V, Destounis, K, Filippo, F, Dima, A, Dimastrogiovanni, E, Dolan, S, Doneva, D, Duque, F, Durrer, R, East, W, Easther, R, Elley, M, Ellis, J, Emparan, R, Ezquiaga, J, Fairbairn, M, Fairhurst, S, Farmer, H, Fasiello, M, Ferrari, V, Ferreira, P, Ficarra, G, Figueras, P, Fisenko, S, Foffa, S, Franchini, N, Franciolini, G, Fransen, K, Frauendiener, J, Frusciante, N, Fujita, R, Gair, J, Ganz, A, Garcia, P, Garcia-Bellido, J, Garriga, J, Geiger, R, Geng, C, Gergely, L, Germani, C, Gerosa, D, Giddings, S, Gourgoulhon, E, Grandclement, P, Graziani, L, Gualtieri, L, Haggard, D, Haino, S, Halburd, R, Han, W, Hawken, A, Hees, A, Heng, I, Hennig, J, Herdeiro, C, Hervik, S, Holten, J, Hoyle, C, Hu, Y, Hull, M, Ikeda, T, Isi, M, Jenkins, A, Julié, F, Kajfasz, E, Kalaghatgi, C, Kaloper, N, Kamionkowski, M, Karas, V, Kastha, S, Keresztes, Z, Kidder, L, Kimpson, T, Klein, A, Klioner, S, Kokkotas, K, Kolesova, H, Kolkowitz, S, Kopp, J, Koyama, K, Krishnendu, N, Kroon, J, Kunz, M, Lahav, O, Landragin, A, Lang, R, Poncin-Lafitte, C, Lemos, J, Li, B, Liberati, S, Liguori, M, Lin, F, Liu, G, Lobo, F, Loll, R, Lombriser, L, Lovelace, G, Macedo, R, Madge, E, Maggio, E, Maggiore, M, Marassi, S, Marcoccia, P, Markakis, C, Martens, W, Martinovic, K, Martins, C, Maselli, A, Mastrogiovanni, S, Matarrese, S, Matas, A, Mavromatos, N, Mazumdar, A, Meerburg, P, Megias, E, Miller, J, Mimoso, J, Mittnacht, L, Montero, M, Moore, B, Martin-Moruno, P, Musco, I, Nakano, H, Nampalliwar, S, Nardini, G, Nielsen, A, Novák, J, Nunes, N, Okounkova, M, Oliveri, R, Oppizzi, F, Orlando, G, Oshita, N, Pappas, G, Paschalidis, V, Peiris, H, Peloso, M, Perkins, S, Pettorino, V, Pikovski, I, Pilo, L, Podolsky, J, Pontzen, A, Prabhat, S, Pratten, G, Prokopec, T, Prouza, M, Qi, H, Raccanelli, A, Rajantie, A, Randall, L, Raposo, G, Raymond, V, Renaux-Petel, S, Ricciardone, A, Riotto, A, Robson, T, Roest, D, Rollo, R, Rosofsky, S, Ruan, J, Rubiera-García, D, Ruiz, M, Rusu, M, Sabatie, F, Sago, N, Sakellariadou, M, Saltas, I, Sberna, L, Sathyaprakash, B, Scheel, M, Schmidt, P, Schutz, B, Schwaller, P, Shao, L, Shapiro, S, Shoemaker, D, Silva, A, Simpson, C, Sopuerta, C, Spallicci, A, Stefanek, B, Stein, L, Stergioulas, N, Stott, M, Sutton, P, Svarc, R, Tagoshi, H, Tahamtan, T, Takeda, H, Tanaka, T, Tantilian, G, Tasinato, G, Tattersall, O, Teukolsky, S, Tiec, A, Theureau, G, Trodden, M, Tolley, A, Toubiana, A, Traykova, D, Tsokaros, A, Unal, C, Unnikrishnan, C, Vagenas, E, Valageas, P, Vallisneri, M, Brand, J, Broeck, C, de Meent, M, Vanhove, P, Varma, V, Veitch, J, Vercnocke, B, Verde, L, Vernieri, D, Vernizzi, F, Vicente, R, Vidotto, F, Visser, M, Vlah, Z, Vretinaris, S, Völkel, S, Wang, Q, Wang, Y, Werner, M, Westernacher, J, Weygaert, R, Wiltshire, D, Wiseman, T, Wolf, P, Wu, K, Yamada, K, Yang, H, Yi, L, Yue, X, Yvon, D, Zilhão, M, Zimmerman, A, Zumalacarregui, M, Barausse, Enrico, Berti, Emanuele, Hertog, Thomas, Hughes, Scott A., Jetzer, Philippe, Pani, Paolo, Sotiriou, Thomas P., Tamanini, Nicola, Witek, Helvi, Yagi, Kent, Yunes, Nicolás, Abdelsalhin, T., Achucarro, A., van Aelst, K., Afshordi, N., Akcay, S., Annulli, L., Arun, K. G., Ayuso, I., Baibhav, V., Baker, T., Bantilan, H., Barreiro, T., Barrera-Hinojosa, C., Bartolo, N., Baumann, D., Belgacem, E., Bellini, E., Bellomo, N., Ben-Dayan, I., Bena, I., Benkel, R., Bergshoefs, E., Bernard, L., Bernuzzi, S., Bertacca, D., Besancon, M., Beutler, F., Beyer, F., Bhagwat, S., Bicak, J., Biondini, S., Bize, S., Blas, D., Boehmer, C., Boller, K., Bonga, B., Bonvin, C., Bosso, P., Bozzola, G., Brax, P., Breitbach, M., Brito, R., Bruni, M., Brügmann, B., Bulten, H., Buonanno, A., Burko, L. M., Burrage, C., Cabral, F., Calcagni, G., Caprini, C., Cárdenas-Avendaño, A., Celoria, M., Chatziioannou, K., Chernoff, D., Clough, K., Coates, A., Comelli, D., Compère, G., Croon, D., Cruces, D., Cusin, G., Dalang, C., Danielsson, U., Das, S., Datta, S., de Boer, J., De Luca, V., De Rham, C., Desjacques, V., Destounis, K., Filippo, F. Di, Dima, A., Dimastrogiovanni, E., Dolan, S., Doneva, D., Duque, F., Durrer, R., East, W., Easther, R., Elley, M., Ellis, J. R., Emparan, R., Ezquiaga, J. M., Fairbairn, M., Fairhurst, S., Farmer, H. F., Fasiello, M. R., Ferrari, V., Ferreira, P. G., Ficarra, G., Figueras, P., Fisenko, S., Foffa, S., Franchini, N., Franciolini, G., Fransen, K., Frauendiener, J., Frusciante, N., Fujita, R., Gair, J., Ganz, A., Garcia, P., Garcia-Bellido, J., Garriga, J., Geiger, R., Geng, C., Gergely, L. Á., Germani, C., Gerosa, D., Giddings, S. B., Gourgoulhon, E., Grandclement, P., Graziani, L., Gualtieri, L., Haggard, D., Haino, S., Halburd, R., Han, W. -B., Hawken, A. J., Hees, A., Heng, I. S., Hennig, J., Herdeiro, C., Hervik, S., Holten, J. v., Hoyle, C. J. D., Hu, Y., Hull, M., Ikeda, T., Isi, M., Jenkins, A., Julié, F., Kajfasz, E., Kalaghatgi, C., Kaloper, N., Kamionkowski, M., Karas, V., Kastha, S., Keresztes, Z., Kidder, L., Kimpson, T., Klein, A., Klioner, S., Kokkotas, K., Kolesova, H., Kolkowitz, S., Kopp, J., Koyama, K., Krishnendu, N. V., Kroon, J. A. V., Kunz, M., Lahav, O., Landragin, A., Lang, R. N., Poncin-Lafitte, C. Le, Lemos, J., Li, B., Liberati, S., Liguori, M., Lin, F., Liu, G., Lobo, F. S. N., Loll, R., Lombriser, L., Lovelace, G., Macedo, R. P., Madge, E., Maggio, E., Maggiore, M., Marassi, S., Marcoccia, P., Markakis, C., Martens, W., Martinovic, K., Martins, C. J. A. P., Maselli, A., Mastrogiovanni, S., Matarrese, S., Matas, A., Mavromatos, N. E., Mazumdar, A., Meerburg, P. D., Megias, E., Miller, J., Mimoso, J. P., Mittnacht, L., Montero, M. M., Moore, B., Martin-Moruno, P., Musco, I., Nakano, H., Nampalliwar, S., Nardini, G., Nielsen, A., Novák, J., Nunes, N. J., Okounkova, M., Oliveri, R., Oppizzi, F., Orlando, G., Oshita, N., Pappas, G., Paschalidis, V., Peiris, H., Peloso, M., Perkins, S., Pettorino, V., Pikovski, I., Pilo, L., Podolsky, J., Pontzen, A., Prabhat, S., Pratten, G., Prokopec, T., Prouza, M., Qi, H., Raccanelli, A., Rajantie, A., Randall, L., Raposo, G., Raymond, V., Renaux-Petel, S., Ricciardone, A., Riotto, A., Robson, T., Roest, D., Rollo, R., Rosofsky, S., Ruan, J. J., Rubiera-García, D., Ruiz, M., Rusu, M., Sabatie, F., Sago, N., Sakellariadou, M., Saltas, I. D., Sberna, L., Sathyaprakash, B., Scheel, M., Schmidt, P., Schutz, B., Schwaller, P., Shao, L., Shapiro, S. L., Shoemaker, D., Silva, A. d., Simpson, C., Sopuerta, C. F., Spallicci, A., Stefanek, B. A., Stein, L., Stergioulas, N., Stott, M., Sutton, P., Svarc, R., Tagoshi, H., Tahamtan, T., Takeda, H., Tanaka, T., Tantilian, G., Tasinato, G., Tattersall, O., Teukolsky, S., Tiec, A. L., Theureau, G., Trodden, M., Tolley, A., Toubiana, A., Traykova, D., Tsokaros, A., Unal, C., Unnikrishnan, C. S., Vagenas, E. C., Valageas, P., Vallisneri, M., Brand, J. Van den, Broeck, C. Van den, de Meent, M. van, Vanhove, P., Varma, V., Veitch, J., Vercnocke, B., Verde, L., Vernieri, D., Vernizzi, F., Vicente, R., Vidotto, F., Visser, M., Vlah, Z., Vretinaris, S., Völkel, S., Wang, Q., Wang, Yu-Tong, Werner, M. C., Westernacher, J., Weygaert, R. v. d., Wiltshire, D., Wiseman, T., Wolf, P., Wu, K., Yamada, K., Yang, H., Yi, L., Yue, X., Yvon, D., Zilhão, M., Zimmerman, A., and Zumalacarregui, M.

Abstract

In this paper, which is of programmatic rather than quantitative nature, we aim to further delineate and sharpen the future potential of the LISA mission in the area of fundamental physics. Given the very broad range of topics that might be relevant to LISA, we present here a sample of what we view as particularly promising directions, based in part on the current research interests of the LISA scientific community in the area of fundamental physics. We organize these directions through a "science-first" approach that allows us to classify how LISA data can inform theoretical physics in a variety of areas. For each of these theoretical physics classes, we identify the sources that are currently expected to provide the principal contribution to our knowledge, and the areas that need further development. The classification presented here should not be thought of as cast in stone, but rather as a fluid framework that is amenable to change with the flow of new insights in theoretical physics.

Published
2020

22. Caution towards spurious off-target signal in 10X Visium spatial transcriptomics assay from potential lncRNAs.

Author

Prakrithi, P, Juwayria, Jain, Deepali, Malik, Prabhat S, and Gupta, Ishaan

Subjects
LINCRNA, NON-coding RNA, GENOMICS, RNA
Abstract

The 10X Genomics spatial transcriptomics platform enables profiling of fresh-frozen (FF) and formalin-fixed paraffin-embedded (FFPE) tissues. FF analysis relies on PolyA capture of RNAs, whereas FFPE analysis uses predesigned probes to capture coding transcripts. While using FFPE spatial data as a 'negative control' for identifying novel noncoding RNAs in FF data, we found that some probes captured spurious signal from both the target gene and potential lncRNAs. The finding was validated across seven published datasets from 10X Genomics and an in-house dataset. We recommend excluding genes captured by the identified 'spurious' probes from further analyses since the off-target signals account for the reported counts, where some of those genes are known to play role in cancer. We further propose to use existing annotations of lncRNA to redesign FFPE capture probes with better specificity. [ABSTRACT FROM AUTHOR]

Published
2023
Full Text
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24. sj-pptx-1-tct-10.1177_15330338221080981 - Supplemental material for Analysis of miR-375-3p, miR-197-3p, and miR-15a-5p Expression and Their Clinical Relevance as Biomarkers in Lung Cancer

Author

Kumar, Sachin, Saikia, Jyoutishman, Sharawat, Surender K., Malik, Prabhat S., Kumar, Sunil, and Mohan, Anant

Subjects
110320 Radiology and Organ Imaging, FOS: Clinical medicine, Biochemistry, 111299 Oncology and Carcinogenesis not elsewhere classified
Abstract

Supplemental material, sj-pptx-1-tct-10.1177_15330338221080981 for Analysis of miR-375-3p, miR-197-3p, and miR-15a-5p Expression and Their Clinical Relevance as Biomarkers in Lung Cancer by Sachin Kumar, Jyoutishman Saikia, Surender K. Sharawat, Prabhat S. Malik, Sunil Kumar and Anant Mohan in Technology in Cancer Research & Treatment

Published
2022
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27. Ventromedial hypothalamic neurons control a defensive emotion state

Author

Prabhat S Kunwar, Moriel Zelikowsky, Ryan Remedios, Haijiang Cai, Melis Yilmaz, Markus Meister, and David J Anderson

Subjects
fear, emotion, defense, ventromedial hypothalamus, persistance, scalability, Medicine, Science, Biology (General), QH301-705.5
Abstract

Defensive behaviors reflect underlying emotion states, such as fear. The hypothalamus plays a role in such behaviors, but prevailing textbook views depict it as an effector of upstream emotion centers, such as the amygdala, rather than as an emotion center itself. We used optogenetic manipulations to probe the function of a specific hypothalamic cell type that mediates innate defensive responses. These neurons are sufficient to drive multiple defensive actions, and required for defensive behaviors in diverse contexts. The behavioral consequences of activating these neurons, moreover, exhibit properties characteristic of emotion states in general, including scalability, (negative) valence, generalization and persistence. Importantly, these neurons can also condition learned defensive behavior, further refuting long-standing claims that the hypothalamus is unable to support emotional learning and therefore is not an emotion center. These data indicate that the hypothalamus plays an integral role to instantiate emotion states, and is not simply a passive effector of upstream emotion centers.

Published
2015
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28. Autologous stem cell transplant for multiple myeloma: Impact of melphalan dose on the transplant outcome.

Author

Kumar, Lalit, Sahoo, Ranjit Kumar, Kumar, Sudhir, Baa, Annie K., Tansir, Ghazal, Pathak, Neha, Malik, Prabhat S., Sharma, Om Dutt, Mathew, Anisha, Jha, Ankit, Gupta, Ritu, Sharma, Atul, Biswas, Ahitagni, Kumar, Rakesh, Thulkar, Sanjay, Malik, Soumyaranjan, and Dutt, Ashish

Subjects
STEM cell transplantation, TREATMENT effectiveness, MULTIPLE myeloma, MELPHALAN, PROGRESSION-free survival
Abstract

We evaluated impact of melphalan dose on transplant outcomes for multiple myeloma. Between 1995 and 2019 459 consecutive patients received a transplant; 69(15%) received melphalan ≤150 mg/m2 (Mel 150 cohort) and 390 (85%) melphalan 200 mg/m2 (MEL 200 cohort). The primary outcome was overall survival (OS) from the date of transplant. Progression-free survival (PFS), engraftment, transplant response, and cumulative relapse at 2 years were secondary outcome measures. Patients in Mel 150 cohort had adverse clinical and laboratory parameters at base line. Transplant response was better for Mel 200 cohort (p < 0.024). Median OS at a median follow-up of 88 months was similar in the two cohorts; 100 Vs 102 months (Mel 200), p = 0.817. Median PFS (60.0 Vs 53 months, p = 0.746), relapse at two years (32.4% Vs 30.9%, p = 0.745) and grade 3-4 mucositis (p = 0.823) were similar. Initial treatment prepares patients better for subsequent similar transplant outcomes despite differences in baseline characteristics. [ABSTRACT FROM AUTHOR]

Published
2023
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30. Evaluation of the programmed death-ligand 1 mRNA expression and immunopositivity and their correlation with survival outcomes in Indian lung cancer patients

Author

Kumar, Sachin, primary, Pandey, Monu, additional, Mir, Ishfaq A., additional, Mukhopadhyay, Abhirup, additional, Sharawat, Surender K., additional, Jain, Deepali, additional, Saikia, Jyoutishman, additional, Malik, Prabhat S., additional, Kumar, Sunil, additional, and Mohan, Anant, additional

Published
2021
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31. Lung Cancer in India

Author

Singh, Navneet, primary, Agrawal, Sushma, additional, Jiwnani, Sabita, additional, Khosla, Divya, additional, Malik, Prabhat S., additional, Mohan, Anant, additional, Penumadu, Prasanth, additional, and Prasad, Kuruswamy Thurai, additional

Published
2021
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33. Case reports

Author

Kim, Mi Jin, Jang, Kee Taek, Choe, Yon Ho, Malik, Prabhat S., Broor, Shobha, Bakhshi, Sameer, Aggarwal, Mukul, Aggarwal, K. C., Karamchand, Aggarwal, Archana, Mundkur, Suneel C., Aroor, Shrikiran, Jayashree, K., Patra, P. K., Nayak, Uma S., Sushma, T. S., Shah, Ira, and Rahangdale, Aarti

Published
2011
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35. Hedgehog does not guide migrating Drosophila germ cells

Author

Renault, Andrew D., Ricardo, Sara, Kunwar, Prabhat S., Santos, Ana, Starz-Gaiano, Michelle, Stein, Jennifer A., and Lehmann, Ruth

Subjects
Phosphates, Coenzymes, Drosophila, Biological sciences
Abstract

To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.ydbio.2009.01.042 Byline: Andrew D. Renault, Sara Ricardo, Prabhat S. Kunwar, Ana Santos, Michelle Starz-Gaiano, Jennifer A. Stein, Ruth Lehmann Keywords: Primordial germ cells; Drosophila; Hedgehog; HMGCoA reductase; tout velu Abstract: In many species, the germ cells, precursors of sperm and egg, migrate during embryogenesis. The signals that regulate this migration are thus essential for fertility. In flies, lipid signals have been shown to affect germ cell guidance. In particular, the synthesis of geranylgeranyl pyrophosphate through the 3-hydroxy-3-methyl-glutaryl coenzyme A reductase (Hmgcr) pathway is critical for attracting germ cells to their target tissue. In a genetic analysis of signaling pathways known to affect cell migration of other migratory cells, we failed to find a role for the Hedgehog (Hh) pathway in germ cell migration. However, previous reports had implicated Hh as a germ cell attractant in flies and suggested that Hh signaling is enhanced through the action of the Hmgcr pathway. We therefore repeated several critical experiments and carried out further experiments to test specifically whether Hh is a germ cell attractant in flies. In contrast to previously reported findings and consistent with findings in zebrafish our data do not support the notion that Hh has a direct role in the guidance of migrating germ cells in flies. Author Affiliation: HHMI and Kimmel Center for Biology and Medicine of the Skirball Institute, Department of Cell Biology, New York University School of Medicine, New York, NY, 10016, USA Article History: Received 14 November 2008; Revised 28 January 2009; Accepted 28 January 2009

Published
2009

37. Stimulus-specific hypothalamic encoding of a persistent defensive state

Author

Ling-yun Li, David J. Anderson, Ann Kennedy, Daniel A. Wagenaar, Stefanos Stagkourakis, and Prabhat S. Kunwar

Subjects
Male, 0301 basic medicine, endocrine system, Time Factors, Hypothalamus, Stimulation, Anxiety, Optogenetics, Stimulus (physiology), Hippocampal formation, Biology, Article, Mice, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Calcium imaging, Animals, Computer Simulation, Neurotransmitter, Neurons, Neurotransmitter Agents, Multidisciplinary, Working memory, Fear, 030104 developmental biology, Acoustic Stimulation, chemistry, Predatory Behavior, Excitatory postsynaptic potential, Calcium, Cues, Neuroscience, 030217 neurology & neurosurgery
Abstract

Persistent neural activity in cortical, hippocampal, and motor networks has been described as mediating working memory for transiently encountered stimuli. Internal emotional states, such as fear, also persist following exposure to an inciting stimulus, but it is unclear whether slow neural dynamics are involved in this process. Neurons in the dorsomedial and central subdivisions of the ventromedial hypothalamus (VMHdm/c) that express the nuclear receptor protein NR5A1 (also known as SF1) are necessary for defensive responses to predators in mice. Optogenetic activation of these neurons, referred to here as VMHdm^(SF1) neurons, elicits defensive behaviours that outlast stimulation, which suggests the induction of a persistent internal state of fear or anxiety. Here we show that in response to naturalistic threatening stimuli, VMHdm^(SF1) neurons in mice exhibit activity that lasts for many tens of seconds. This persistent activity was correlated with, and required for, persistent defensive behaviour in an open-field assay, and depended on neurotransmitter release from VMHdm^(SF1) neurons. Stimulation and calcium imaging in acute slices showed that there is local excitatory connectivity between VMHdm^(SF1) neurons. Microendoscopic calcium imaging of VMHdm^(SF1) neurons revealed that persistent activity at the population level reflects heterogeneous dynamics among individual cells. Unexpectedly, distinct but overlapping VMHdm^(SF1) subpopulations were persistently activated by different modalities of threatening stimulus. Computational modelling suggests that neither recurrent excitation nor slow-acting neuromodulators alone can account for persistent activity that maintains stimulus identity. Our results show that stimulus-specific slow neural dynamics in the hypothalamus, on a time scale orders of magnitude longer than that of working memory in the cortex, contribute to a persistent emotional state.

Published
2020

38. The Drosophila actin regulator ENABLED regulates cell shape and orientation during gonad morphogenesis.

Author

Hiroko Sano, Prabhat S Kunwar, Andrew D Renault, Vitor Barbosa, Ivan B N Clark, Shuji Ishihara, Kaoru Sugimura, and Ruth Lehmann

Subjects
Medicine, Science
Abstract

Organs develop distinctive morphologies to fulfill their unique functions. We used Drosophila embryonic gonads as a model to study how two different cell lineages, primordial germ cells (PGCs) and somatic gonadal precursors (SGPs), combine to form one organ. We developed a membrane GFP marker to image SGP behaviors live. These studies show that a combination of SGP cell shape changes and inward movement of anterior and posterior SGPs leads to the compaction of the spherical gonad. This process is disrupted in mutants of the actin regulator, enabled (ena). We show that Ena coordinates these cell shape changes and the inward movement of the SGPs, and Ena affects the intracellular localization of DE-cadherin (DE-cad). Mathematical simulation based on these observations suggests that changes in DE-cad localization can generate the forces needed to compact an elongated structure into a sphere. We propose that Ena regulates force balance in the SGPs by sequestering DE-cad, leading to the morphogenetic movement required for gonad compaction.

Published
2012
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39. Prospects for fundamental physics with LISA

Author

Theoretical Physics, Sub NMR Spectroscopy, LS Immunologie, Afd Subatomic Physics (SAP), Afd OT Educatie en pedagogiek, Sub General Pharmaceutics, Sub RvdM overig, Sub String Theory Cosmology and ElemPart, Dep Natuurkunde, Sub Inorganic Chemistry and Catalysis, LS Wijsgerige Ethiek, Section Geography and Education, Barausse, Enrico, Berti, Emanuele, Hertog, Thomas, Hughes, Scott A., Jetzer, Philippe, Pani, Paolo, Sotiriou, Thomas P., Tamanini, Nicola, Witek, Helvi, Yagi, Kent, Yunes, Nicolas, Abdelsalhin, T., Achucarro, A., van Aelst, K., Afshordi, N., Akcay, S., Annulli, L., Arun, K. G., Ayuso, I., Baibhav, V., Baker, T., Bantilan, H., Barreiro, T., Barrera-Hinojosa, C., Bartolo, N., Baumann, D., Belgacem, E., Bellini, E., Bellomo, N., Ben-Dayan, I., Bena, I., Benkel, R., Bergshoefs, E., Bernard, L., Bernuzzi, S., Bertacca, D., Besancon, M., Beutler, F., Beyer, F., Bhagwat, S., Bicak, J., Biondini, S., Bize, S., Blas, D., Boehmer, C., Boller, K., Bonga, B., Bonvin, C., Bosso, P., Bozzola, G., Brax, P., Breitbach, M., Brito, R., Bruni, M., Bruegmann, B., Bulten, H., Buonanno, A., Burko, L. M., Burrage, C., Cabral, F., Calcagni, G., Caprini, C., Cardenas-Avendano, A., Celoria, M., Chatziioannou, K., Chernoff, D., Clough, K., Coates, A., Comelli, D., Compere, G., Croon, D., Cruces, D., Cusin, G., Dalang, C., Danielsson, U., Das, S., Datta, S., de Boer, J., De Luca, V., De Rham, C., Desjacques, V., Destounis, K., Filippo, F. Di, Dima, A., Dimastrogiovanni, E., Dolan, S., Doneva, D., Duque, F., Durrer, R., East, W., Easther, R., Elley, M., Ellis, J. R., Emparan, R., Ezquiaga, J. M., Fairbairn, M., Fairhurst, S., Farmer, H. F., Fasiello, M. R., Ferrari, V., Ferreira, P. G., Ficarra, G., Figueras, P., Fisenko, S., Foffa, S., Franchini, N., Franciolini, G., Fransen, K., Frauendiener, J., Frusciante, N., Fujita, R., Gair, J., Ganz, A., Garcia, P., Garcia-Bellido, J., Garriga, J., Geiger, R., Geng, C., Gergely, L. a., Germani, C., Gerosa, D., Giddings, S. B., Gourgoulhon, E., Grandclement, P., Graziani, L., Gualtieri, L., Haggard, D., Haino, S., Halburd, R., Han, W. -B., Hawken, A. J., Hees, A., Heng, I. S., Hennig, J., Herdeiro, C., Hervik, S., Holten, J. v., Hoyle, C. D., Hu, Y., Hull, M., Ikeda, T., Isi, M., Jenkins, A., Julie, F., Kajfasz, E., Kalaghatgi, C., Kaloper, N., Kamionkowski, M., Karas, V., Kastha, S., Keresztes, Z., Kidder, L., Kimpson, T., Klein, A., Klioner, S., Kokkotas, K., Kolesova, H., Kolkowitz, S., Kopp, J., Koyama, K., Krishnendu, N. V., Kroon, J. A. V., Kunz, M., Lahav, O., Landragin, A., Lang, R. N., Poncin-Lafitte, C. Le, Lemos, J., Li, B., Liberati, S., Liguori, M., Lin, F., Liu, G., Lobo, F. S. N., Loll, R., Lombriser, L., Lovelace, G., Macedo, R. P., Madge, E., Maggio, E., Maggiore, M., Marassi, S., Marcoccia, P., Markakis, C., Martens, W., Martinovic, K., Martins, C. J. A. P., Maselli, A., Mastrogiovanni, S., Matarrese, S., Matas, A., Mavromatos, N. E., Mazumdar, A., Meerburg, P. D., Megias, E., Miller, J., Mimoso, J. P., Mittnacht, L., Montero, M. M., Moore, B., Martin-Moruno, P., Musco, I., Nakano, H., Nampalliwar, S., Nardini, G., Nielsen, A., Novak, J., Nunes, N. J., Okounkova, M., Oliveri, R., Oppizzi, F., Orlando, G., Oshita, N., Pappas, G., Paschalidis, V., Peiris, H., Peloso, M., Perkins, S., Pettorino, V., Pikovski, I., Pilo, L., Podolsky, J., Pontzen, A., Prabhat, S., Pratten, G., Prokopec, T., Prouza, M., Qi, H., Raccanelli, A., Rajantie, A., Randall, L., Raposo, G., Raymond, V., Renaux-Petel, S., Ricciardone, A., Riotto, A., Robson, T., Roest, D., Rollo, R., Rosofsky, S., Ruan, J. J., Rubiera-Garcia, D., Ruiz, M., Rusu, M., Sabatie, F., Sago, N., Sakellariadou, M., Saltas, I. D., Sberna, L., Sathyaprakash, B., Scheel, M., Schmidt, P., Schutz, B., Schwaller, P., Shao, L., Shapiro, S. L., Shoemaker, D., Silva, A. d., Simpson, C., Sopuerta, C. F., Spallicci, A., Stefanek, B. A., Stein, L., Stergioulas, N., Stott, M., Sutton, P., Svarc, R., Tagoshi, H., Tahamtan, T., Takeda, H., Tanaka, T., Tantilian, G., Tasinato, G., Tattersall, O., Teukolsky, S., Tiec, A. L., Theureau, G., Trodden, M., Tolley, A., Toubiana, A., Traykova, D., Tsokaros, A., Unal, C., Unnikrishnan, C. S., Vagenas, E. C., Valageas, P., Vallisneri, M., Brand, J. Van den, Broeck, C. Van den, de Meent, M. van, Vanhove, P., Varma, V., Veitch, J., Vercnocke, B., Verde, L., Vernieri, D., Vernizzi, F., Vicente, R., Vidotto, F., Visser, M., Vlah, Z., Vretinaris, S., Voelkel, S., Wang, Q., Wang, Yu-Tong, Werner, M. C., Westernacher, J., Weygaert, R. v. d., Wiltshire, D., Wiseman, T., Wolf, P., Wu, K., Yamada, K., Yang, H., Yi, L., Yue, X., Yvon, D., Zilhao, M., Zimmerman, A., Zumalacarregui, M., Theoretical Physics, Sub NMR Spectroscopy, LS Immunologie, Afd Subatomic Physics (SAP), Afd OT Educatie en pedagogiek, Sub General Pharmaceutics, Sub RvdM overig, Sub String Theory Cosmology and ElemPart, Dep Natuurkunde, Sub Inorganic Chemistry and Catalysis, LS Wijsgerige Ethiek, Section Geography and Education, Barausse, Enrico, Berti, Emanuele, Hertog, Thomas, Hughes, Scott A., Jetzer, Philippe, Pani, Paolo, Sotiriou, Thomas P., Tamanini, Nicola, Witek, Helvi, Yagi, Kent, Yunes, Nicolas, Abdelsalhin, T., Achucarro, A., van Aelst, K., Afshordi, N., Akcay, S., Annulli, L., Arun, K. G., Ayuso, I., Baibhav, V., Baker, T., Bantilan, H., Barreiro, T., Barrera-Hinojosa, C., Bartolo, N., Baumann, D., Belgacem, E., Bellini, E., Bellomo, N., Ben-Dayan, I., Bena, I., Benkel, R., Bergshoefs, E., Bernard, L., Bernuzzi, S., Bertacca, D., Besancon, M., Beutler, F., Beyer, F., Bhagwat, S., Bicak, J., Biondini, S., Bize, S., Blas, D., Boehmer, C., Boller, K., Bonga, B., Bonvin, C., Bosso, P., Bozzola, G., Brax, P., Breitbach, M., Brito, R., Bruni, M., Bruegmann, B., Bulten, H., Buonanno, A., Burko, L. M., Burrage, C., Cabral, F., Calcagni, G., Caprini, C., Cardenas-Avendano, A., Celoria, M., Chatziioannou, K., Chernoff, D., Clough, K., Coates, A., Comelli, D., Compere, G., Croon, D., Cruces, D., Cusin, G., Dalang, C., Danielsson, U., Das, S., Datta, S., de Boer, J., De Luca, V., De Rham, C., Desjacques, V., Destounis, K., Filippo, F. Di, Dima, A., Dimastrogiovanni, E., Dolan, S., Doneva, D., Duque, F., Durrer, R., East, W., Easther, R., Elley, M., Ellis, J. R., Emparan, R., Ezquiaga, J. M., Fairbairn, M., Fairhurst, S., Farmer, H. F., Fasiello, M. R., Ferrari, V., Ferreira, P. G., Ficarra, G., Figueras, P., Fisenko, S., Foffa, S., Franchini, N., Franciolini, G., Fransen, K., Frauendiener, J., Frusciante, N., Fujita, R., Gair, J., Ganz, A., Garcia, P., Garcia-Bellido, J., Garriga, J., Geiger, R., Geng, C., Gergely, L. a., Germani, C., Gerosa, D., Giddings, S. B., Gourgoulhon, E., Grandclement, P., Graziani, L., Gualtieri, L., Haggard, D., Haino, S., Halburd, R., Han, W. -B., Hawken, A. J., Hees, A., Heng, I. S., Hennig, J., Herdeiro, C., Hervik, S., Holten, J. v., Hoyle, C. D., Hu, Y., Hull, M., Ikeda, T., Isi, M., Jenkins, A., Julie, F., Kajfasz, E., Kalaghatgi, C., Kaloper, N., Kamionkowski, M., Karas, V., Kastha, S., Keresztes, Z., Kidder, L., Kimpson, T., Klein, A., Klioner, S., Kokkotas, K., Kolesova, H., Kolkowitz, S., Kopp, J., Koyama, K., Krishnendu, N. V., Kroon, J. A. V., Kunz, M., Lahav, O., Landragin, A., Lang, R. N., Poncin-Lafitte, C. Le, Lemos, J., Li, B., Liberati, S., Liguori, M., Lin, F., Liu, G., Lobo, F. S. N., Loll, R., Lombriser, L., Lovelace, G., Macedo, R. P., Madge, E., Maggio, E., Maggiore, M., Marassi, S., Marcoccia, P., Markakis, C., Martens, W., Martinovic, K., Martins, C. J. A. P., Maselli, A., Mastrogiovanni, S., Matarrese, S., Matas, A., Mavromatos, N. E., Mazumdar, A., Meerburg, P. D., Megias, E., Miller, J., Mimoso, J. P., Mittnacht, L., Montero, M. M., Moore, B., Martin-Moruno, P., Musco, I., Nakano, H., Nampalliwar, S., Nardini, G., Nielsen, A., Novak, J., Nunes, N. J., Okounkova, M., Oliveri, R., Oppizzi, F., Orlando, G., Oshita, N., Pappas, G., Paschalidis, V., Peiris, H., Peloso, M., Perkins, S., Pettorino, V., Pikovski, I., Pilo, L., Podolsky, J., Pontzen, A., Prabhat, S., Pratten, G., Prokopec, T., Prouza, M., Qi, H., Raccanelli, A., Rajantie, A., Randall, L., Raposo, G., Raymond, V., Renaux-Petel, S., Ricciardone, A., Riotto, A., Robson, T., Roest, D., Rollo, R., Rosofsky, S., Ruan, J. J., Rubiera-Garcia, D., Ruiz, M., Rusu, M., Sabatie, F., Sago, N., Sakellariadou, M., Saltas, I. D., Sberna, L., Sathyaprakash, B., Scheel, M., Schmidt, P., Schutz, B., Schwaller, P., Shao, L., Shapiro, S. L., Shoemaker, D., Silva, A. d., Simpson, C., Sopuerta, C. F., Spallicci, A., Stefanek, B. A., Stein, L., Stergioulas, N., Stott, M., Sutton, P., Svarc, R., Tagoshi, H., Tahamtan, T., Takeda, H., Tanaka, T., Tantilian, G., Tasinato, G., Tattersall, O., Teukolsky, S., Tiec, A. L., Theureau, G., Trodden, M., Tolley, A., Toubiana, A., Traykova, D., Tsokaros, A., Unal, C., Unnikrishnan, C. S., Vagenas, E. C., Valageas, P., Vallisneri, M., Brand, J. Van den, Broeck, C. Van den, de Meent, M. van, Vanhove, P., Varma, V., Veitch, J., Vercnocke, B., Verde, L., Vernieri, D., Vernizzi, F., Vicente, R., Vidotto, F., Visser, M., Vlah, Z., Vretinaris, S., Voelkel, S., Wang, Q., Wang, Yu-Tong, Werner, M. C., Westernacher, J., Weygaert, R. v. d., Wiltshire, D., Wiseman, T., Wolf, P., Wu, K., Yamada, K., Yang, H., Yi, L., Yue, X., Yvon, D., Zilhao, M., Zimmerman, A., and Zumalacarregui, M.

Published
2020

41. Safety of osimertinib in adult patients with metastatic epidermal growth factor receptor T790M mutation‑positive non‑small cell lung cancer: Results from a Phase IV study in India.

Author

Malik, Prabhat S., Noronha, Vanita, Dabkara, Deepak, Maddu, Vamshi K., Rajappa, Senthil, Limaye, Sewanti, and Batra, Ullas

Subjects
*EPIDERMAL growth factor receptors, *NON-small-cell lung carcinoma, *CHEST pain, *OSIMERTINIB, *CREATINE kinase
Abstract

Background: A Phase IV, single‑arm study was conducted to assess the safety of osimertinib in Indian patients with epidermal growth factor receptor (EGFR) T790M mutation‑positive stage IV non‑small cell lung cancer (NSCLC). Methods: Enrolled patients received 80 mg osimertinib for six cycles or until disease progression or unacceptable toxicity or withdrawal. Primary safety variables included treatment‑emergent adverse events (TEAEs), serious adverse events(SAEs), and adverse events(AEs) leading to discontinuation/interruption/change (D/I/C) of drug dose, and AEs of special interest (AESIs). AEs were summarized by the percentage of patients experiencing at least one occurrence of each event. Results: Of the 60 enrolled patients (median age 58 [range: 34–81] years; 51.7% women) at eight sites, nine patients were discontinued prematurely due to disease progression (n = 7) and death (n = 2); median (range) duration of treatment was 126 (1–134) days. Median age of patients was 58 (34–81) years; 51.7% (n = 31) were women; 86.7% (n = 52) were nonsmokers; and most of them (98.3%) had adenocarcinoma. About 75% (n = 45) of patients experienced any of the TEAEs, with the most frequent being fatigue and creatine phosphokinase (CPK) increase (n = 6, 10% each). TEAEs in 11 (18.3%) patients were judged as study treatment related, with CPK increase being the most common (n = 4, 6.7%). TEAEs led to D/I/C of drug dose in eight (13.3%) patients, with one being study treatment related. Nine (15%) patients had AESIs of dyspnea (n = 6), chest pain (n = 2), and cardiorespiratory arrest (n = 1); two of them had a fatal outcome. One AESI (mild dyspnea) was considered study drug related. TEAEs of grade ≥3 were reported in seven (11.7%) patients, including dyspnea in two (3.3%), followed by diarrhea, mucosal inflammation, cardiorespiratory arrest, and others (n = 1, 1.7% each). None of the SAEs and fatal events were considered as study treatment related. Seven (11.7%) patients had abnormal electrocardiogram (ECG; not clinically significant) at the end of the study. Conclusion: Our study confirms the favorable safety profile of osimertinib without any new safety concerns in Indian patients with EGFR T790M mutation‑positive stage IV NSCLC. [ABSTRACT FROM AUTHOR]

Published
2022
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43. Prospects for fundamental physics with LISA

Author

Barausse, Enrico, primary, Berti, Emanuele, additional, Hertog, Thomas, additional, Hughes, Scott A., additional, Jetzer, Philippe, additional, Pani, Paolo, additional, Sotiriou, Thomas P., additional, Tamanini, Nicola, additional, Witek, Helvi, additional, Yagi, Kent, additional, Yunes, Nicolás, additional, Abdelsalhin, T., additional, Achucarro, A., additional, van Aelst, K., additional, Afshordi, N., additional, Akcay, S., additional, Annulli, L., additional, Arun, K. G., additional, Ayuso, I., additional, Baibhav, V., additional, Baker, T., additional, Bantilan, H., additional, Barreiro, T., additional, Barrera-Hinojosa, C., additional, Bartolo, N., additional, Baumann, D., additional, Belgacem, E., additional, Bellini, E., additional, Bellomo, N., additional, Ben-Dayan, I., additional, Bena, I., additional, Benkel, R., additional, Bergshoefs, E., additional, Bernard, L., additional, Bernuzzi, S., additional, Bertacca, D., additional, Besancon, M., additional, Beutler, F., additional, Beyer, F., additional, Bhagwat, S., additional, Bicak, J., additional, Biondini, S., additional, Bize, S., additional, Blas, D., additional, Boehmer, C., additional, Boller, K., additional, Bonga, B., additional, Bonvin, C., additional, Bosso, P., additional, Bozzola, G., additional, Brax, P., additional, Breitbach, M., additional, Brito, R., additional, Bruni, M., additional, Brügmann, B., additional, Bulten, H., additional, Buonanno, A., additional, Burko, L. M., additional, Burrage, C., additional, Cabral, F., additional, Calcagni, G., additional, Caprini, C., additional, Cárdenas-Avendaño, A., additional, Celoria, M., additional, Chatziioannou, K., additional, Chernoff, D., additional, Clough, K., additional, Coates, A., additional, Comelli, D., additional, Compère, G., additional, Croon, D., additional, Cruces, D., additional, Cusin, G., additional, Dalang, C., additional, Danielsson, U., additional, Das, S., additional, Datta, S., additional, de Boer, J., additional, De Luca, V., additional, De Rham, C., additional, Desjacques, V., additional, Destounis, K., additional, Filippo, F. Di, additional, Dima, A., additional, Dimastrogiovanni, E., additional, Dolan, S., additional, Doneva, D., additional, Duque, F., additional, Durrer, R., additional, East, W., additional, Easther, R., additional, Elley, M., additional, Ellis, J. R., additional, Emparan, R., additional, Ezquiaga, J. 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Published
2020
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44. Clinical predictors of response to EGFR-tyrosine kinase inhibitors in EGFR-mutated non-small cell lung cancer: A real-world multicentric cohort analysis from India

Author

Garg, Avneet, primary, Batra, Ullas, additional, Choudhary, Priyanshu, additional, Jain, Deepali, additional, Khurana, Sachin, additional, Malik, Prabhat S., additional, Muthu, Valliappan, additional, Prasad, K.T., additional, Singh, Navneet, additional, Suri, Tejas, additional, and Mohan, Anant, additional

Published
2020
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48. Tre1, a G protein-coupled receptor, directs transepithelial migration of Drosophila germ cells.

Author

Prabhat S Kunwar, Michelle Starz-Gaiano, Roland J Bainton, Ulrike Heberlein, and Ruth Lehmann

Subjects
Biology (General), QH301-705.5
Abstract

In most organisms, germ cells are formed distant from the somatic part of the gonad and thus have to migrate along and through a variety of tissues to reach the gonad. Transepithelial migration through the posterior midgut (PMG) is the first active step during Drosophila germ cell migration. Here we report the identification of a novel G protein-coupled receptor (GPCR), Tre1, that is essential for this migration step. Maternal tre1 RNA is localized to germ cells, and tre1 is required cell autonomously in germ cells. In tre1 mutant embryos, most germ cells do not exit the PMG. The few germ cells that do leave the midgut early migrate normally to the gonad, suggesting that this gene is specifically required for transepithelial migration and that mutant germ cells are still able to recognize other guidance cues. Additionally, inhibiting small Rho GTPases in germ cells affects transepithelial migration, suggesting that Tre1 signals through Rho1. We propose that Tre1 acts in a manner similar to chemokine receptors required during transepithelial migration of leukocytes, implying an evolutionarily conserved mechanism of transepithelial migration. Recently, the chemokine receptor CXCR4 was shown to direct migration in vertebrate germ cells. Thus, germ cells may more generally use GPCR signaling to navigate the embryo toward their target.

Published
2003
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49. Stimulus-specific neural encoding of a persistent, internal defensive state in the hypothalamus

Author

Ann Kennedy, David J. Anderson, Daniel A. Wagenaar, Prabhat S. Kunwar, and Li L

Subjects
0303 health sciences, education.field_of_study, Working memory, Population, Hippocampal formation, Stimulus (physiology), Biology, Optogenetics, 03 medical and health sciences, 0302 clinical medicine, Recurrent neural network, Neurochemical, Hypothalamus, education, Neuroscience, 030217 neurology & neurosurgery, 030304 developmental biology
Abstract

SummaryPersistent neural activity has been described in cortical, hippocampal, and motor networks as mediating short-term working memory of transiently encountered stimuli1–4. Internal emotion states such as fear also exhibit persistence following exposure to an inciting stimulus5,6, but such persistence is typically attributed to circulating stress hormones7–9; whether persistent neural activity also plays a role has not been established. SF1+/Nr5a1+ neurons in the dorsomedial and central subdivision of the ventromedial hypothalamus (VMHdm/c) are necessary for innate and learned defensive responses to predators10–13. Optogenetic activation of VMHdmSF1 neurons elicits defensive behaviors that can outlast stimulation11,14, suggesting it induces a persistent internal state of fear or anxiety. Here we show that VMHdmSF1 neurons exhibit persistent activity lasting tens of seconds, in response to naturalistic threatening stimuli. This persistent activity was correlated with, and required for, persistent thigmotaxic (anxiety-like) behavior in an open-field assay. Microendoscopic imaging of VMHdmSF1 neurons revealed that persistence reflects dynamic temporal changes in population activity, rather than simply synchronous, slow decay of simultaneously activated neurons. Unexpectedly, distinct but overlapping VMHdmSF1 subpopulations were persistently activated by different classes of threatening stimuli. Computational modeling suggested that recurrent neural networks (RNNs) incorporating slow excitation and a modest degree of neurochemical or spatial bias can account for persistent activity that maintains stimulus identity, without invoking genetically determined “labeled lines”15. Our results provide causal evidence that persistent neural activity, in addition to well-established neuroendocrine mechanisms, can contribute to the ability of emotion states to outlast their inciting stimuli, and suggest a mechanism that could prevent over-generalization of defensive responses without the need to evolve hardwired circuits specific for each type of threat.

Published
2019

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