Recent advances in metal directed C-H amidation/amination using sulfonyl azides and phosphoryl azides.

Transition metal-catalyzed C-N bond formation reactions have gained popularity as a method for selectively transforming common C-H bonds into N-functionalized molecules. This approach is particularly useful for synthesizing aminated molecules, which require aminating reagents and amidated building blocks. Over the past two decades, significant advancements have been achieved in transition-metal-catalyzed C-H functionalization, with organic azides emerging as promising amino sources and internal oxidants. This review focuses on recent developments in utilizing sulfonyl and phosphoryl azides as building blocks for directed intra- and intermolecular C-H functionalization reactions. Specifically, it discusses methods for synthesizing sulfonamidates and phosphoramidates using sulfonyl and phosphoryl azides, respectively. The article highlights the potential of C-H functionalization reactions with organic azides for efficiently and sustainably synthesizing N-functionalized molecules, providing valuable insights into the latest advancements in this field.

Development of prospective hospital-based venous thromboembolism registry across India: a study protocol.

INTRODUCTION: Indian Council of Medical Research (ICMR), New Delhi has established a nationwide registry 'Indian Registry for Venous Thromoembolism Disorder (i-RegVeD)' for real-time analytics of sociodemographic profile of patients, disease patterns, management strategies, treatment choices and outcomes of patients with venous thromboemobolism (VTE). The purpose is to generate evidence on VTE in order to fill the gaps in the knowledge of the disease across various demographic regions. METHODS AND ANALYSIS: This prospective hospital-based registry will be a continuous data collection process on the occurrence and characteristics of VTE from the 16 hospital sites pan India. This process would include obtaining clinical profiles, risk factors, diagnostic tests, treatment and outcome information of patients collected from medical records through an active method of data abstraction and data capture mechanism guided by an online web-based tool. ETHICS AND DISSEMINATION: At centralised programme management unit, the study protocol was approved by the Institutional Ethics Committees (IEC) named ICMR-Central Ethics Committee on Human Research and similarly each of the participating site has obtained the ethical approval by their respective IECs. The results from this study will be disseminated publicly on the study website (https://iregved.icmr.org.in) as well as through scientific meetings and publications.

Subspecialization, Senior Residency, or Private Practice: The Dilemma of Final-Year Radiology Postgraduate Residents in India.

Background Radiology is among India's top five speciality choices pursued by meritorious medical graduates. With the advent of the subspecialization degree courses, fellowships, the requirement of senior residency as faculty eligibility criteria, and the lucrative option of private practice, the final-year postgraduates are given opportunities to choose from but with little guidance on what and how to choose. This study aims to analyze the views of the final-year radiology postgraduate residents in India regarding their understanding of how to proceed in their professional life with options available. Materials and Methods A cross-sectional, questionnaire-based study was conducted online via Google forms distributed via email and social media platforms. The questionnaire was prepared after going through previous literature, video blogs, and media available on the Internet and was further validated for content. Results About half (48%) of them wished to pursue higher studies in the form of Doctorate of Medicine (DM) degree courses or fellowships. Almost three-quarters of the participants preferred short-term subspecialization via fellowships over 3-year DM courses (28%). Regarding clinical practice, 61.9% preferred to take up senior residency, while slightly over one-third (35.7%) expressed their will to move on to private practice. Conclusion A relative conundrum was observed in the decision to take up senior residency or private practice or to go for DM but had to pursue a fellowship due to limited choice in topics and seats available in the country for subspecialization.

Expedited diagnosis of pediatric tuberculosis using Truenat MTB-Rif Dx and GeneXpert MTB/RIF.

Rapid, cost-effective, and sensitive diagnostic assays are essential for global tuberculosis (TB) control, especially in high TB burden, resource-limited settings. The current study was designed to evaluate diagnostic accuracy of Truenat MTB-Rif Dx (MolBio) in children less than 18 years of age, with symptoms suggestive of TB. Gastric aspirate, induced sputum, and broncho-alveolar lavage samples were subjected simultaneously to AFB-smear, GeneXpert MTB/RIF, liquid culture (MGIT-960) and Truenat MTB-Rif Dx. The index-test results were evaluated against microbiological reference standards (MRS). Truenat MTB-Rif Dx had a sensitivity of 57.1%, specificity of 92% against MRS. The sensitivity and specificity of the Truenat MTB-RIF Dx compared with liquid culture was 58.7% and 87.5% while GeneXpert MTB/RIF was 56% and 91.4%. The performance of both GeneXpert MTB/RIF and Truenat MTB-Rif Dx are comparable. Result of our study demonstrates that Truenat MTB-Rif can aid in early and efficient diagnosis of TB in children.

Reducing Perinatal Mortality in India: Two-Years Results of the IRIA Fetal Radiology Samrakshan Program.

Aim The aim of the study is to determine improvements in perinatal mortality at the end of the first 2 years from the initiation of the Samrakshan program of the Indian Radiological and Imaging Association. Methods Samrakshan is a screening program of pregnant women that uses trimester-specific risk assessment protocols including maternal demographics, mean arterial pressure, and fetal Doppler studies to classify women as high risk or low risk for preterm preeclampsia (PE) and fetal growth restriction (FGR). Low dose aspirin 150 mg daily once at bedtime was started for pregnant women identified as high risk in the 11-13 6/7 weeks screening. The third-trimester screening focused on the staging of FGR and protocol-based management for childbirth and risk assessment for PE. Outcomes of childbirth including gestational age at delivery, development of PE, and perinatal mortality outcomes were collected. Results Radiologists from 38 districts of 16 states of India participated in the Samrakshan program that screened 2,816 first trimester, 3,267 second trimester, and 3,272 third trimester pregnant women, respectively. At 2 years, preterm PE was identified in 2.76%, preterm births in 19.28%, abnormal Doppler study in 25.76% of third trimester pregnancies, and 75.32% of stage 1 FGR delivered at term. The neonatal mortality rate was 9.86/1,000 live births, perinatal mortality rate was 18.97/1,000 childbirths, and maternal mortality was 58/100,000 live births compared with 29.5, 36, and 113, respectively in 2016. Conclusion Fetal Doppler integrated antenatal ultrasound studies in Samrakshan led to a significant reduction in preterm PE rates, preterm birth rates, and a significant improvement in mean birth weights. Perinatal, neonatal, and maternal mortality rates are significantly better than the targets for 2030 set by the Sustainable Development Goals-3.

Noise Robust Detection of Fundamental Heart Sound using Parametric Mixture Gaussian and Dynamic Programming.

In this work, we propose an unsupervised algorithm for fundamental heart sound detection. We propose to detect the heart sound candidates using the stationary wavelet transforms and group delay. We further propose an objective function to select the candidates. The objective function has two parts. We model the energy contour of S1/S2 sound using the Gaussian mixture function (GMF). The goodness of fit for the GMF is used as the first part of the objective function. The second part of the objective function captures the consistency of the heart sounds' relative location. We solve the objective function efficiently using dynamic programming. We evaluate the algorithm on Michigan HeartSound and Murmur database. We also assess the algorithm's performance using the three different additive noises- white Gaussian noise (AWGN), Student-t noise, and impulsive noise. The experiments demonstrate that the proposed method performs better than baseline in both clean and noisy conditions. We found that the proposed method is robust in the case of AWGN noise and student-t distribution noise. But its performance reduces in case of impulsive noise.

Unsegmented Heart Sound Classification Using Hybrid CNN-LSTM Neural Networks.

Cardiac Auscultation, an integral part of the physical examination of a patient, is essential for early diagnosis of cardiovascular diseases (CVDs). The ability to accurately diagnose the heart sounds requires experience and expertise, which is lacking in doctors in the early years of clinical practice. Thus, there is a need for an automatic diagnostic tool that would aid medical practitioners with their diagnosis. We propose novel hybrid architectures for classification of unsegmented heart sounds to normal and abnormal classes. We propose two methods, with and without the conventional feature extraction step in the classification pipeline. We demonstrate that the F score using the approach with conventional feature extraction is 1.25 (absolute) more than using a baseline implementation on the Physionet dataset. We also introduce a mechanism to tag predictions as unsure and compare results with a varying threshold.

Trends in packaging material for food products: historical background, current scenario, and future prospects.

The commercial demand for food products and dietary supplements has increased drastically in the last few decades. The packed food products and nutritional supplements have made a profound impact on the modern human lifestyle. Since ancient times, storage and long-term use of food products remain a significant challenge for humans. There are different parameters for the evaluation of food products and dietary supplements broadly categorized as quality control and quality assurance. On an average million tons of food, materials get spoiled daily worldwide due to lack of storage and transportation point out packaging systems inequalities. To ensure the quality of packed food products and nutritional supplements among available measures, packaging remained an important event and had been refined from time to time to provide a standard. Over a period, the packaging industry has evolved using modern technology from the conventional methods of new generation packaging, including glass, wood, and paper to most new biodegradable materials. The ancient pattern of packaging; manual packaging has been taken over by an automated system of packing, resulting in enhanced output with minimal chance of damage to valuable products for humanity. The article will emphasize new insights into current packaging system not only provide the quality of these products but also in aiming new heights beyond conventional technologies and consumer opinions. In the present study, we have given more emphasis on novel methods of packaging, the packaging materials, quality of packed products, and their impacts of food products on the environment.

Reusable Nano-Zirconia-Catalyzed Synthesis of Benzimidazoles and Their Antibacterial and Antifungal Activities.

In this article, a zirconia-based nano-catalyst (Nano-ZrO2), with intermolecular C-N bond formation for the synthesis of various benzimidazole-fused heterocycles in a concise method is reported. The robustness of this reaction is demonstrated by the synthesis of a series of benzimidazole drugs in a one-pot method. All synthesized materials were characterized using 1HNMR, 13CNMR, and LC-MS spectroscopy as well as microanalysis data. Furthermore, the synthesis of nano-ZrO2 was processed using a standard hydrothermal technique in pure form. The crystal structure of nano-ZrO2 and phase purity were studied, and the crystallite size was calculated from XRD analysis using the Debye-Scherrer equation. Furthermore, the antimicrobial activity of the synthesized benzimidazole drugs was evaluated in terms of Gram-positive, Gram-negative, and antifungal activity, and the results were satisfactory.

Analyzing the Changes in Certain Infectious and Parasitic Diseases in Urban Population of India By Using Medical Certification of Cause of Death Data.

BACKGROUND: Infectious diseases are important causes of morbidity and mortality globally. At least 25% of about 60 million deaths that occur worldwide each year are estimated to be due to infectious diseases. In India, the burden of infectious diseases is enormous; although it has decreased as a result of overall socioeconomic progress and use of vaccines and antimicrobials, it is still a major health-care burden. Studying a disease trend over a certain time period is important in a country's public health system as it guides agencies to prioritize funds and other measures for its control. OBJECTIVES: The present study tries to understand its transition in an urban population of India. MATERIALS AND METHODS: "Medical Certification of Cause of Death" data for the period from 1989 to 2015 have been used. Deaths under the head "age not stated" have been distributed in all age groups in proportion to total deaths at those age groups for all the years, and the percentage of the cause of death to total deaths has been calculated. Three years' moving average of these percentages have been calculated. RESULTS: The overall age group analysis showed a downward trend in both males and females. However, age-segregated analysis showed that mortality is declining among children and youth population, specifically showing a steep decline among infants and under-five population. CONCLUSION: Infectious diseases are still a major public health problem in India.

In-Silico Drug Designing of Spike Receptor with Its ACE2 Receptor and Nsp10/Nsp16 MTase Complex Against SARS-CoV-2.

The realm Riboviria constitutes Coronaviruses, which led to the emergence of the pandemic COVID 19 in the twenty-first century affected millions of lives. At present, the management of COVID 19 largely depends on antiviral therapeutics along with the anti-inflammatory drug. The vaccine is under the final clinical phase, and emergency use is available. We aim at ACE2 and Nsp10/Nsp16 MTase as potential drug candidate in COVID 19 management in the present work. For drug designing, various computational simulation strategies have been employed like Swiss-Model, Hawk Dock, HDOCK, py Dock, and PockDrug for homology modeling, binding energies of the molecule with a target, simulate the conformation and binding poses, statistics of protein lock with target key and drug ability, respectively. The current in-silico screening depicts that the spike protein receptor is complementary to the target when bound to each other and forms a stable complex. The MMGBSA free energy binding property of receptor and ligand is critical. The intermolecular Statistics with the target Nsp10/Nsp16 MTase complex are plausible. We have also observed a high-affinity pocket binding site with the target. Therefore, the favorable intermolecular interactions and Physico-chemical properties emanate as a drug candidate treating COVID-19. This study has approached computational tools to analyze the conformation, binding affinity, and drug ability of receptor-ligand. Thus, the spike receptor with its ACE2 receptor with Nsp10/Nsp16 MTase complex would be a potent drug against SARS CoV-2 and can cure the infection as per consensus scoring.

Multicentric validation of indigenous molecular test Truenat™ MTB for detection of Mycobacterium tuberculosis in sputum samples from presumptive pulmonary tuberculosis patients in comparison with reference standards.

BACKGROUND & OBJECTIVES: : Early case detection is essential to interrupt transmission and to prevent further spread of tuberculosis (TB) in high endemic settings. Nucleic acid amplification tests (NAATs) with visual read-outs are ideal as point-of-care tests. Truenat™ MTB is an indigenous chip-based NAAT for detection of Mycobacterium tuberculosis, which involves extraction of DNA and real-time polymerase chain reaction (PCR) using portable, automated, battery-operated instruments. The current multicentric study was aimed to evaluate Truenat for detection of MTB in sputum samples obtained from patients with presumptive pulmonary TB with reference to culture as gold standard and Xpert as a comparator. METHODS: : The study was conducted at four sites, namely ICMR-National Institute for Research in Tuberculosis, Chennai; All India Institute of Medical Sciences, New Delhi; ICMR-National JALMA Institute for Leprosy and Other Mycobacterial Diseases, Agra; and National Institute of TB and Respiratory Diseases, New Delhi. Patients suspected to have TB were screened for eligibility. Two sputum samples were collected from each patient. Tests included smear, Xpert and Truenat directly from the sputum sample and culture by Lowenstein-Jensen (L-J) medium and MGIT960 from decontaminated pellets. Sample used for Truenat assay was coded. Resolution of Truenat false positives was done using an in-house PCR with TRC4 primers. RESULTS: : The study enrolled 2419 presumptive TB patients after screening 2465 patients, and 3541 sputum samples were collected from the enrolled patients. Results of 2623 samples were available for analysis. Truenat showed a positivity rate of 48.5 per cent as compared to 37.0 per cent by Xpert. The sensitivities of Truenat and Xpert were was 88.3 and 79.7 per cent, respectively in comparison with culture. INTERPRETATION & CONCLUSIONS: : Truenat MTB identified more positives among culture-confirmed samples than Xpert and had higher sensitivity. In addition, other advantageous operational features of Truenat MTB were identified which would be useful in field settings.

Lymphomatous Interstitial Nephritis Coexistent with Paraneoplastic Crescentic Membranoproliferative Glomerulonephritis in a Case of Mantle Cell Lymphoma.

Mantle cell lymphoma (MCL) is a rare aggressive lymphoproliferative disorders (LPD) of B-cell lymphoma, which usually presents in advanced stages at initial diagnosis. Renal involvement in MCL is very rare, especially the combined presence of both glomerular and interstitial disease. We report on a patient with lymphomatous interstitial nephritis (LIN) coexistent with paraneoplastic crescentic membranoproliferative glomerulonephritis (MPGN), subsequently diagnosed to have disseminated MCL with bone marrow and lymph nodal infiltration. He was treated with rituximab-based chemotherapy and went into complete renal remission at 6-months of follow up.

Two step convolutional neural network for automatic glottis localization and segmentation in stroboscopic videos.

Precise analysis of the vocal fold vibratory pattern in a stroboscopic video plays a key role in the evaluation of voice disorders. Automatic glottis segmentation is one of the preliminary steps in such analysis. In this work, it is divided into two subproblems namely, glottis localization and glottis segmentation. A two step convolutional neural network (CNN) approach is proposed for the automatic glottis segmentation. Data augmentation is carried out using two techniques :  1) Blind rotation (WB), 2) Rotation with respect to glottis orientation (WO). The dataset used in this study contains stroboscopic videos of 18 subjects with Sulcus vocalis, in which the glottis region is annotated by three speech language pathologists (SLPs). The proposed two step CNN approach achieves an average localization accuracy of 90.08% and a mean dice score of 0.65.

CRISPR-Cas9 mediated genome editing of drought and salt tolerance (OsDST) gene in indica mega rice cultivar MTU1010.

Development of abiotic stress tolerant rice cultivars is necessary for sustainable rice production under the scenario of global climate change, dwindling fresh water resources and increase in salt affected areas. Several genes from rice have been functionally validated by using EMS mutants and transgenics. Often, many of these desirable alleles are not available indica rice which is mainly cultivated, and where available, introgression of these alleles into elite cultivars is a time and labour intensive process, in addition to the potential introgression of non-desirable genes due to linkage. CRISPR-Cas technology helps development of elite cultivars with desirable alleles by precision gene editing. Hence, this study was carried out to create mutant alleles of drought and salt tolerance (DST) gene by using CRISPR-Cas9 gene editing in indica rice cv. MTU1010. We used two different gRNAs to target regions of DST protein that might be involved in protein-protein interaction and successfully generated different mutant alleles of DST gene. We selected homozygous dst mutant with 366 bp deletion between the two gRNAs for phenotypic analysis. This 366 bp deletion led to the deletion of amino acid residues from 184 to 305 in frame, and hence the mutant was named as dst ∆184-305 . The dst ∆184-305 mutation induced by CRISPR-Cas9 method in DST gene in indica rice cv. MTU1010 phenocopied EMS-induced dst (N69D) mutation reported earlier in japonica cultivar. The dst ∆184-305 mutant produced leaves with broader width and reduced stomatal density, and thus enhanced leaf water retention under dehydration stress. Our study showed that the reduction in stomatal density in loss of function mutants of dst is, at least, in part due to downregulation of stomatal developmental genes SPCH1, MUTE and ICE1. The Cas9-free dst ∆184-305 mutant exhibited moderate level tolerance to osmotic stress and high level of salt stress in seedling stage. Thus, dst mutant alleles generated in this study will be useful for improving drought and salt tolerance and grain yield in indica rice cultivars.

Seeing beyond the gut: An unusual cause of massive hematemesis.

We report the clinical details, imaging findings, and management of a 74-year-old male who had recurrent episodes of massive hematemesis secondary to rupture of a cavernous internal carotid artery (ICA) aneurysm. Ruptured ICA aneurysms may present with epistaxis. However, intracranial aneurysmal rupture with hematemesis as the presenting complaint has not been described previously in the literature. In this case report we describe the pathophysiology of cerebral aneurysm as a cause of hematemesis and its management.

DNA barcoding and genetic fidelity assessment of micropropagated Aenhenrya rotundifolia (Blatt.) C.S. Kumar and F.N. Rasm.: a critically endangered jewel orchid.

Aenhenrya rotundifolia is a critically endangered terrestrial jewel orchid. It is monotypic and endemic to evergreen forests of southern western ghats of India. In the present study, identification of this plant species is validated with DNA barcoding using matK and rbcL chloroplast markers. Further, germ-free juvenile axillary bud explants were cultured on Mitra medium supplemented with different kinds of cytokinins like 6-benzyladenine, 6-furfurylaminopurine, N6-(Δ2-isopentyl) adenine, thidiazuron, zeatin and meta-topolin as well as auxins such as α-naphthaleneacetic acid, indole-3-acetic acid and indole-3-butyric acid at different concentrations and combinations for successful proliferation and establishment in vitro. After 12 weeks of culture, axillary bud explants produced an average of 30.12 ± 0.71 shoots per explant, 3.87 ± 0.06 cm shoot length, 1671 ± 2.82 mg fresh mass of proliferated shoots with a proliferation frequency of 100% on Mitra medium supplemented with 6.20 µM meta-topolin and 2.25 µM thidiazuron. No root formation was observed in in vitro proliferated microshoots. However, tiny hair like projections were observed in some elongated shoots on Mitra medium pertaining to 5.37 µM NAA. The tiny hair like structure bearing plantlets were hardened and acclimatized with 100% survival rate in the polytunnel chamber. After 8-10 months of establishment ex vitro, flowering was observed. Additionally, the genetic fidelity of in vitro derived plants was tested with ISSR and SCoT marker profiling. The test results revealed that the plants derived from the protocol has 99% genetic similarity to that of the donor mother plant. This study can be applied in forensic interventions of this species, describes the maintenance of germplasm in vitro and establishment of new viable population in its original habitats by restoring existing sites of this critically endangered jewel orchid.

Validation of an indigenous assay for rapid molecular detection of rifampicin resistance in presumptive multidrug-resistant pulmonary tuberculosis patients.

BACKGROUND & OBJECTIVES: There is a need for an affordable, easy, high-sensitivity test usable at the peripheral health facility for diagnosis of drug-resistant (DR) tuberculosis (TB) to interrupt disease transmission. Nucleic acid amplification tests (NAATs) for early detection of DR-TB are ideal to bring testing near to the patient. TruenatTM MTB (Mycobacterium tuberculosis) and TruenatTM MTB-RIF (rifampicin) is an indigenous chip-based real-time polymerase chain reaction (PCR) based test for detection of multidrug-resistant (MDR) TB. The test involves extraction of DNA using automated, battery operated Trueprep instrument and real-time PCR performed on the Truelab analyzer. We report here multicentric validation of Truenat MTB-RIF for detection of DR-TB in suspected DR-TB patients. METHODS: Consecutive patients aged 18-65 yr, with symptoms suggestive of TB and with a history of previous treatment, reporting to the National TB Elimination Programme (NTEP) clinics under four national institutes, namely AIIMS (All India Institute of Medical Sciences, New Delhi), NITRD (National Institute of Tuberculosis and Respiratory Diseases, New Delhi), NIRT (National Institute for Research in Tuberculosis, Chennai) and ICMR-National JALMA Institute for Leprosy and other Mycobacterial Diseases, Agra, were included in the study. Two sputum samples (one spot and one morning) were collected from each patient, after obtaining informed written consent. The samples were subjected to smear, GeneXpert and MGIT 960 culture (and drug susceptibility testing to RIF) (surrogate for MDR-TB) to serve as reference tests. The samples were coded to ensure blinding and subjected to Truenat MTB-RIF. Truenat MTB-RIF Version 1.5 was used for testing 1084 samples for RIF resistance, while Version 2.0 was used to test another 1201 samples. RESULTS: Truenat MTB-RIF Version 1.5 in comparison with comprehensive laboratory reference standards yielded sensitivity and specificity of 76.2 and 94.7 per cent, respectively for the detection of RIF resistance in 1084 samples, collected across four sites. Based on the analysis of discordant samples, Version 2.0 of Truenat was developed by the manufacturer and this was further tested on additional 1201 samples, yielding a sensitivity of 87.5 per cent and specificity of 99.5 per cent. INTERPRETATION & CONCLUSIONS: Multicentric trial of TruenatTM MTB-RIF demonstrated a great potential of this point of care NAAT for detection of MDR-TB. The test would be useful in limited resource settings and inaccessible areas without need for any additional infrastructure.