Selection bias obfuscates the discovery of fast radio burst sources.

Fast radio bursts (FRBs) are a newly discovered class of extragalactic radio transients characterized by their high energy and short duration (from microseconds to milliseconds)1. The physical origin of these FRBs remains unknown and is a subject of ongoing research, with magnetars emerging as leading candidates2,3. Previous studies have used various methodologies to address the problem of FRB origin, including demographic analyses of FRB host galaxies and their local environments4-6, assessments of FRB rate evolution with redshift7-9 and searches for proposed multi-messenger FRB counterparts10. However, these studies are susceptible to substantial biases stemming from unaccounted radio and optical selection effects. Here we present empirical evidence for a substantial selection bias against detecting FRBs in galaxies with large inclination angles (edge-on) using a sample of hosts identified for FRBs discovered by untargeted surveys. This inclination-related bias probably leads to a significant underestimation (by about a factor of two) of the FRB rates reported in the literature and disfavours globular clusters as the dominant origin of FRB sources, as previously speculated6. These conclusions have important implications for FRB progenitor models and targeted FRB follow-up strategies. We further investigate the impact of this bias on the relative rate of FRBs in different host environments. Our analysis suggests that scattering in FRB hosts is probably responsible for the observed bias11,12. However, a larger sample of localized FRBs is required to robustly quantify the contribution of scattering to the inclination-related selection bias.

Sub-second periodicity in a fast radio burst.

Fast radio bursts (FRBs) are millisecond-duration flashes of radio waves that are visible at distances of billions of light years1. The nature of their progenitors and their emission mechanism remain open astrophysical questions2. Here we report the detection of the multicomponent FRB 20191221A and the identification of a periodic separation of 216.8(1) ms between its components, with a significance of 6.5σ. The long (roughly 3 s) duration and nine or more components forming the pulse profile make this source an outlier in the FRB population. Such short periodicity provides strong evidence for a neutron-star origin of the event. Moreover, our detection favours emission arising from the neutron-star magnetosphere3,4, as opposed to emission regions located further away from the star, as predicted by some models5.

Evaluation of medicinal herbs as a potential therapeutic option against SARS-CoV-2 targeting its main protease.

The COVID-19 disease caused by the SARS-CoV-2 has emerged as a worldwide pandemic and caused huge damage to the lives and economy of more than hundred countries. As on May 10, 2020, more than 4,153,300 people stand infected from the virus due to an unprecedented rate of transmission and 282,700 have lost their lives because of the disease. In this context, medicinal plants may provide a way to treat the disease by targeting specific essential proteins of the virus. We screened about 51 medicinal plants and found that Tea (Camellia sinensis) and Haritaki (Terminalia chebula) has potential against SARS-COV-2 3CLpro , with an IC50 for Green Tea as 8.9 ± 0.5 µg/ml and Haritaki 8.8 ± 0.5 µg/ml. The in-silico studies suggested that Tea component Thearubigins binds to the cysteine 145 of protease active site and could be a pharmacoactive molecule. We predict that the inhibition in protease activity may be able to halt the SARS-CoV-2 replication cycle and therefore, we propose Green Tea, Black Tea, and Haritaki plant extracts as potential therapeutic candidates for SARS-CoV-2 infection. Further investigation on role of bioactive constituents of extracts is needed to establish the molecular basis of inhibition and towards expedited drug discovery.

Three-way Philadelphia Translocation [t(46, XX, t(9;22;16) (q34;q11.2;q24)] in Chronic Myeloid Leukemia: A Report of Two Cases with Review of the Literature.

ABSTRACT: Chronic myeloid leukemia (CML) is a clonal myeloproliferative neoplasm that is genetically characterized by the presence of the Philadelphia (Ph) chromosome. Variant Ph translocation has been observed in 5% to 10% of the CML cases. In the previous studies, many different types of variant Ph translocations have been observed involving chromosomes 1p36, 3p21, 5q13, 6p21, 9q22, 11q13, 12p13, 17p13, and 10p15. According to the published literature, only two cases with the complex translocations involving long arm of chromosome 16 at band q24 have been reported. We report two female patients with complex translocation (three-way) involving chromosomes 9, 22, and 16 at breakpoint q24 and both patients responded well to Imatinib. The present study included 469 patients of clinically diagnosed CML patients who were referred for cytogenetic analysis to our laboratory. Cytogenetic analysis was performed by GTG banding, and the karyotype was designated according to the International System for Human Cytogenetic Nomenclature. Fluorescence in situ hybridization (FISH) analysis was performed for complex and variant BCR-ABL cases. Of total 469 cases, 248 patients showed classical Ph chromosome [t(9;22)(q34;q11.2)], 198 cases were normal, and 23 patients had variant and complex Ph chromosome translocation. Two patients showed three-way translocation involving long arm of chromosomes 9, 22, and 16 at band 9q34, 22q11.2, and 16q24. In this report, patients with variant Ph translocation did not have a significantly different outcome as compared to the classical translocation. Both cases responded well to Imatinib.

Awareness and Readiness To Implement the Pradhan Mantri Jan Arogya Yojana: A Cross-Sectional Study Among Healthcare Workers of a Tertiary Care Hospital in Eastern India.

Background The Indian government announced "Ayushman Bharat" for a New India 2022 during the 2018-19 parliament budget sessions, which includes the national health protection scheme presently known as "Pradhan Mantri Jan Arogya Yojana (PMJAY)" to facilitate access to secondary and tertiary healthcare services. This study aimed to see how well healthcare workers (HCWs) understood the PMJAY and how prepared they were to administer it. Materials and methods With an anticipated sample size of 411, this hospital-based analytical, cross-sectional study was done among treating faculty, resident doctors, and nursing officers as study participants. Participants completed a self-administered, pre-tested, semi-structured questionnaire to determine their level of awareness and readiness to adopt PMJAY. SPSS Version 22 software (SPSS Inc., Chicago, IL, USA) was used to analyze the data. Results The overall mean (SD) awareness score and mean readiness score among HCWs were found to be 5.52 (1.82) and 18.49 (4.5), respectively. There was a significantly high awareness score among doctors compared to nursing officers. The relation between awareness score and readiness score showed a weak positive significant correlation (r=0.174, p=0.001). The linear regression model demonstrated an increase of 0.432 units in readiness for every unit increase in awareness score. Conclusion The doctor's mean awareness score was little over half of the maximum attainable score. Faculty members were more aware of the scheme than the residents and nursing officers. The readiness to implement PMJAY improves as the awareness grows. Frequent workshops on PMJAY for stakeholders are required for better readiness.

Correlation of ROS1 (D4D6) Immunohistochemistry with ROS1 Fluorescence In Situ Hybridization Assay in a Contemporary Cohort of Pulmonary Adenocarcinomas.

Sambit K. MohantyObjective Repressor of Silencing ( ROS1 ) gene rearrangement in the lung adenocarcinomas is one of the targetable mutually exclusive genomic alteration. Fluorescence in situ hybridization (FISH), immunohistochemistry (IHC), next-generation sequencing, and reverse transcriptase polymerase chain reaction assays are generally used to detect ROS1 gene alterations. We evaluated the correlation between ROS1 IHC and FISH analysis considering FISH as the gold standard method to determine the utility of IHC as a screening method for lung adenocarcinoma. Materials and Methods A total of 374 advanced pulmonary adenocarcinoma patients were analyzed for ROS1 IHC on Ventana Benchmark XT platform using D4D6 rabbit monoclonal antibody. FISH assay was performed in parallel in all these cases using the Vysis ROS1 Break Apart FISH probe. Statistical Analysis The sensitivity, specificity, positive and negative likelihood ratios, positive and negative predictive values, and accuracy were evaluated. Results A total of 17 tumors were positive either by IHC or FISH analysis or both (true positive). Four tumors were positive by IHC (H-score range: 120-270), while negative on FISH analysis (false positive by IHC). One tumor was IHC negative, but positive by FISH analysis (false negative). The sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, positive predictive value, negative predictive value, and accuracy were 94.4% (confidence interval [CI]: 72.71-99.86%), 63.6% (CI: 30.79-89.07%), 2.6 (CI: 1.18-5.72), 0.09 (CI: 0.01-0.62), 80.95% (CI: 65.86-90.35%), 87.5% (CI: 49.74-98.02%), and 82.76%, respectively. Conclusion ROS1 IHC has high sensitivity at a cost of lower specificity for the detection of ROS1 gene rearrangement. All IHC positive cases should undergo a confirmatory FISH test as this testing algorithm stands as a reliable and economic tool to screen ROS1 rearrangement in lung adenocarcinomas.

Solitary Fibrous Tumor of the Adrenal Gland.

OBJECTIVES: Solitary fibrous tumor (SFT) is a mesenchymal neoplasm that can arise at various anatomic locations. It is characterized by inv12(q13q13)-derived NAB2::STAT6 fusion, resulting in the nuclear expression of STAT6. Primary SFT of the adrenal gland is rare. We launched a multi-institutional collaboration to comprehend the overarching demographics, clinical and follow-up, macroscopic, microscopic, IHC, and FISH features of 9 patients with SFT of the adrenal gland. METHODS: We added a series of 9 patients to the collection of adrenal SFTs where the clinicopathologic parameters, including clinical presentation, imaging, histopathology, IHC, molecular profiles, and management and follow-up data, were analyzed comprehensively. A modified 4-variable risk stratification model, including age, tumor size, and necrosis, was applied. RESULTS: Our series consisted of 6 male and 3 female patients, ranging in age from 19 to 64 years (mean, 49.3 years). Abdominal pain (4) and fever with abdominal pain (1) were the presenting symptoms in 5 patients. In the remaining 4 patients, the tumors were detected by abdominal imaging for hypertension and diabetes. The size of the tumor ranged from 2 cm to 10.5 cm in maximum dimension. All tumors exhibited the morphology of a spindle cell SFT with a patternless architecture; 3 had a focal storiform arrangement. STAT6 positivity was observed in all tumors, and 7 were positive for CD34. Surgical resection was the primary modality of treatment. No adjuvant therapy was administered. Follow-up ranging from 7 months to 23 months was available for 7 patients. All were alive without disease recurrence or metastasis. Risk stratification placed 8 (88.9%) patients into a low-risk category and 1 into an intermediate-risk category. CONCLUSIONS: This series is the largest of adrenal SFTs to date. These tumors of the adrenal gland are predominantly spindle cell neoplasms with indolent behavior, with a wide age distribution and a slight male preponderance. Combining our cohort with the previously published cases, the majority of tumors fall into the low-risk category for the propensity to develop metastases. Owing to the rarity and age distribution associated with these tumors, the differential diagnosis is wide and requires a systematic approach for ruling out key differential diagnoses aided by STAT6 IHC.

Antimicrobial resistance in patients with suspected urinary tract infections in primary care in Assam, India.

OBJECTIVES: We investigated the prevalence and diversity of antimicrobial resistance in bacteria isolated from urine samples of community-onset urinary tract infection (UTI) patients in southern Assam, India. METHODS: Freshly voided midstream urine samples were collected from patients attending primary healthcare centres, with the patients' epidemiological data also recorded. Species identification was confirmed using a VITEK 2 compact automated system. Phenotypic confirmation of ESBLs was performed using the combined disc diffusion method (CLSI 2017) and carbapenemase production was phenotypically characterized using a modified Hodge test. Common ESBLs and carbapenem-resistance mechanisms were determined in Escherichia coli isolates using PCR assays. Incompatibility typing of the conjugable plasmids was determined by PCR-based replicon typing; the phylotypes and MLSTs were also analysed. RESULTS: A total of 301 (59.7%) samples showed significant bacteriuria along with symptoms of UTI and among them 103 isolates were identified as E. coli of multiple STs (ST3268, ST3430, ST4671 and others). Among them, 26.2% (27/103) were phenotypically ESBL producers whereas 12.6% (13/103) were carbapenemase producers. This study describes the occurrence of diverse ESBL genes-bla CTX-M-15, bla SHV-148, bla PER-1 and bla TEM-and two E. coli isolates carrying the bla NDM-1 carbapenemase gene. ESBL genes were located within transconjugable plasmids of IncP and IncF type whereas bla NDM-1 was carried in an IncFrepB type plasmid. CONCLUSIONS: This study illustrates the high rate of MDR in E. coli causing UTI in primary care in rural Assam. UTIs caused by ESBL- or MBL-producing bacteria are very difficult to treat and can often lead to treatment failure. Thus, future research should focus on rapid diagnostics to enable targeted treatment options and reduce the treatment failure likely to occur with commonly prescribed antibiotics, which will help to combat antimicrobial resistance and the burden of UTIs.

Integrated solutions to manage new normals in healthcare-lessons from corona virus disease 2019.

Global outbreak of the corona virus disease 2019 (COVID19) has not only challenged the existing healthcare systems but is also a threat to the world economy and stability. In the recent times the world has seen the best healthcare systems collapsing due to the overwhelming burden. Thus, it shows that there have been major lacunae in the pandemic preparedness across the globe. Hence, there is an urgent need to identify the problems, learn from failures and to prepare for future pandemics to reduce the loss of lives and livelihood. In the modern era, blend of public healthcare systems, medical sciences and technology can be put to use to provide solutions. In this article, the authors propose a developmental model of international integrated database software which would connect all the players involved in the management of a pandemic. Better networking and warning system is a key to successful containment of a new viral outbreak.

Reappraisal of HER2 Amplification in High-Grade Urothelial Carcinoma Based on 2018 ASCO/CAP Clinical Practice Guidelines.

OBJECTIVES: To examine and compare human epidermal growth factor receptor 2 (HER2) amplification status in high-grade urothelial carcinoma (HGUCa), using both 2013 and 2018 HER2 reporting guidelines for breast carcinoma from the American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP). METHODS: HER2 status by fluorescence in situ hybridization (FISH) assay in 78 cases of HGUCa was compared using 2013 and 2018 HER2 reporting guidelines. RESULTS: HER2 amplification was observed in 22 (28.2%) of 78 tumors, of which 17 were in group 1, 1 in group 2, and 2 each in groups 3 and 4 (FISH assay, 2018). The remaining 14 HER2-amplified tumors (FISH assay, 2013) became negative, falling into group 2 (FISH assay, 2018) and were either negative or equivocal on immunohistochemistry (IHC, 2018). All FISH-negative tumors (n = 37) using 2013 criteria remained negative (group 5, 2018). FISH-equivocal tumors (2013) were further categorized into HER2 amplified (n = 1) and HER2 negative (n = 4) (2018). Overall, 20 (25.6%) tumors had discordant HER2 FISH results (2018 vs 2013). CONCLUSIONS: Implementing 2018 guidelines, HER2 amplification decreased from 36 to 22 cases. The group with a HER2/CEP17 ratio of 2 or more and average HER2 copy number less than 4 (group 2) were predominantly negative by IHC, suggesting a biologically distinct group of HGUCa that is different from HER2-amplified tumors, which may not respond to HER2-targeted therapy.

Screening and evaluation of approved drugs as inhibitors of main protease of SARS-CoV-2.

The COVID-19 pandemic caused by SARS-CoV-2 has emerged as a global catastrophe. The virus requires main protease for processing the viral polyproteins PP1A and PP1AB translated from the viral RNA. In search of a quick, safe and successful therapeutic agent; we screened various clinically approved drugs for the in-vitro inhibitory effect on 3CLPro which may be able to halt virus replication. The methods used includes protease activity assay, fluorescence quenching, surface plasmon resonance (SPR), Thermofluor® Assay, Size exclusion chromatography and in-silico docking studies. We found that Teicoplanin as most effective drug with IC50 ~ 1.5 µM. Additionally, through fluorescence quenching Stern-Volmer quenching constant (KSV) for Teicoplanin was estimated as 2.5 × 105 L·mol-1, which suggests a relatively high affinity between Teicoplanin and 3CLPro protease. The SPR shows good interaction between Teicoplanin and 3CLPro with KD ~ 1.6 µM. Our results provide critical insights into the mechanism of action of Teicoplanin as a potential therapeutic against COVID-19. We found that Teicoplanin is about 10-20 fold more potent in inhibiting protease activity than other drugs in use, such as lopinavir, hydroxychloroquine, chloroquine, azithromycin, atazanavir etc. Therefore, Teicoplanin emerged as the best inhibitor among all drug molecules we screened against 3CLPro of SARS-CoV-2.

Insecticidal and wormicidal plants from Aravalli hill range of India.

ETHNOPHARMACOLOGICAL RELEVANCE: Various plants are being used as ethnomedicines against insects and worms in Aravalli hill range of India. In this study, we are focusing upon intellectual traditional ecological knowledge with an objective of revaluation of ethnomedicinal data processing for the plants being utilized against insects and worms. These plants can be explored for drug discovery program against insects and worms. MATERIALS AND METHODS: An ethnobotanical survey was carried out to raise the information on plants against insects and worms from ethnic tribes. The information about the plant part used, dose & mode of administration was collected and verified by interviewing at different times, tribes and places within the study area. RESULTS: 67 remedies with 49 plants species belonging to 29 families are identified and reported with taxonomic description. Mitragyna parvifolia (Roxb.) Korth. is first time reported with ethnomedicinal claims (against insects and worms). CONCLUSION: These plants may specially be selected for the drug discovery program against insects and worms. Active ingredients from these plants may serve as novel drug molecules. Beside conservation efforts to these plants there is an urgent need to document the ethnomedicinal knowledge. The survey provides a veritable source of information for traditional medical practitioners and medicinal plant researchers and help in developing strategies for future conservation.