PTFSpot: deep co-learning on transcription factors and their binding regions attains impeccable universality in plants.

Unlike animals, variability in transcription factors (TFs) and their binding regions (TFBRs) across the plants species is a major problem that most of the existing TFBR finding software fail to tackle, rendering them hardly of any use. This limitation has resulted into underdevelopment of plant regulatory research and rampant use of Arabidopsis-like model species, generating misleading results. Here, we report a revolutionary transformers-based deep-learning approach, PTFSpot, which learns from TF structures and their binding regions' co-variability to bring a universal TF-DNA interaction model to detect TFBR with complete freedom from TF and species-specific models' limitations. During a series of extensive benchmarking studies over multiple experimentally validated data, it not only outperformed the existing software by >30% lead but also delivered consistently >90% accuracy even for those species and TF families that were never encountered during the model-building process. PTFSpot makes it possible now to accurately annotate TFBRs across any plant genome even in the total lack of any TF information, completely free from the bottlenecks of species and TF-specific models.

miWords: transformer-based composite deep learning for highly accurate discovery of pre-miRNA regions across plant genomes.

Discovering pre-microRNAs (miRNAs) is the core of miRNA discovery. Using traditional sequence/structural features, many tools have been published to discover miRNAs. However, in practical applications like genomic annotations, their actual performance has been very low. This becomes more grave in plants where unlike animals pre-miRNAs are much more complex and difficult to identify. A huge gap exists between animals and plants for the available software for miRNA discovery and species-specific miRNA information. Here, we present miWords, a composite deep learning system of transformers and convolutional neural networks which sees genome as a pool of sentences made of words with specific occurrence preferences and contexts, to accurately identify pre-miRNA regions across plant genomes. A comprehensive benchmarking was done involving >10 software representing different genre and many experimentally validated datasets. miWords emerged as the best one while breaching accuracy of 98% and performance lead of ~10%. miWords was also evaluated across Arabidopsis genome where also it outperformed the compared tools. As a demonstration, miWords was run across the tea genome, reporting 803 pre-miRNA regions, all validated by small RNA-seq reads from multiple samples, and most of them were functionally supported by the degradome sequencing data. miWords is freely available as stand-alone source codes at https://scbb.ihbt.res.in/miWords/index.php.

Role of Transporters and Enzymes in Metabolism and Distribution of 4-Chlorokynurenine (AV-101).

4-Chlorokynurenine (4-Cl-KYN, AV-101) is a prodrug of a NMDA receptor antagonist and is in clinical development for potential CNS indications. We sought to further understand the distribution and metabolism of 4-Cl-KYN, as this information might provide a strategy to enhance the clinical development of this drug. We used excretion studies in rats, in vitro transporter assays, and pharmacogenetic analysis of clinical trial data to determine how 4-Cl-KYN and metabolites are distributed. Our data indicated that a novel acetylated metabolite (N-acetyl-4-Cl-KYN) did not affect the uptake of 4-Cl-KYN across the blood-brain barrier via LAT1. 4-Cl-KYN and its metabolites were found to be renally excreted in rodents. In addition, we found that N-acetyl-4-Cl-KYN inhibited renal and hepatic transporters involved in excretion. Thus, this metabolite has the potential to limit the excretion of a range of compounds. Our pharmacogenetic analysis found that a SNP in N-acetyltransferase 8 (NAT8, rs13538) was linked to levels of N-acetyl-4-Cl-KYN relative to 4-Cl-KYN found in the plasma and that a SNP in SLC7A5 (rs28582913) was associated with the plasma levels of the active metabolite, 7-Cl-KYNA. Thus, we have a pharmacogenetics-based association for plasma drug level that could aid in the drug development of 4-Cl-KYN and have investigated the interaction of a novel metabolite with drug transporters.

A Comparative Analysis of Low Dose Grafalon® Versus Thymoglobuline® as Serotherapy in Hematopoietic Stem Cell Transplant in Pediatric and Young Adult Population.

Anti-thymocyte globulin (ATG) forms an essential component of conditioning in hematopoietic stem cell transplantation (HSCT). Due to the shift of donor preference to alternate donors, reliance on rabbit-ATG (rATG) has increased. Two different forms of rATG (Thymoglobuline® and Grafalon®) are available for clinical use but data to support the use of one over the other is sparse. We retrospectively analyzed data of 144 patients who underwent allogenic-HSCT for benign hematological conditions at our center, from August 2019 to August 2023. Of these, 87 received Grafalon® and 57 received Thymoglobuline®. The majority (77.7%) underwent HSCT for hemoglobinopathies and all received pre-transplant immunosuppression. Engraftment kinetics was similar in 2 cohorts. Six patients had primary graft failure (PGF). There was no difference in the incidence of PGF stratified by serotherapy. Overall survival(OS) for the cohort was 74.9%. Kaplan-Meier estimate of OSand EFSwas significantly better in Grafalon® group than Thymoglobuline® (84.4 ± 0.04% vs 64.1% ±0.065%) (p-value= 0.04%) and (84.4 ± 0.04% and 61.2%±0.065% (p-value = 0.01)). Extensive chronic GVHD was (14%) higher in Thymoglobuline® group and (2.3%) in Grafalon®. Immune reconstitution at day + 100 was not statistically different between the two groups. On univariate analysis, Thymoglobuline® serotherapy (OR (95% CI) =4.665 (1.2-18.04))was associated with increased risk of acute grade III-IV GvHD. In our study, Grafalon® tended to have better OS, decreased incidence of acute grade III-IV GvHD, and extensive cGVHD. There was no difference in engraftment kinetics, PGF, and immune reconstitution between 2 cohorts of serotherapy.

Morphological, phytochemical, and transcriptome analyses provide insights into the biosynthesis of monoterpenes in Monarda citriodora.

MAIN CONCLUSION: Morphological, phytochemical, and transcriptome analyses revealed candidate genes involved in the biosynthesis of volatile monoterpenes and development of glandular trichomes in Monarda citriodora. Monarda citriodora Cerv. ex Lag. is a valuable aromatic plant due to the presence of monoterpenes as major constituents in its essential oil (EO). Thus, it is of sheer importance to gain knowledge about the site of the biosynthesis of these terpenoid compounds in M. citriodora, as well as the genes involved in their biosynthesis. In this study, we studied different types of trichomes and their relative densities in three different developmental stages of leaves, early stage of leaf development (L1), mid-stage of leaf development (L2), and later stage of leaf development (L3) and the histochemistry of trichomes for the presence of lipid and terpenoid compounds. Further, the phytochemical analysis of this plant through GC-MS indicated a higher content of monoterpenes (thymol, thymoquinone, γ-terpinene, p-cymene, and carvacrol) in the L1 stage with a substantial decrease in the L3 stage of leaf development. This considerable decrease in the content of monoterpenes was attributed to the decrease in the trichome density from L1 to L3. Further, we developed a de novo transcriptome assembly by carrying out RNA sequencing of different plant parts of M. citriodora. The transcriptome data revealed several putative unigenes involved in the biosynthesis of specialized terpenoid compounds, as well as regulatory genes involved in glandular trichome development. The data generated in the present study build a strong foundation for further improvement of M. citriodora, in terms of quantity and quality of its essential oil, through genetic engineering.

Approach to Di/Triorganotin(IV) Cations via Hydrolysis of Stannate Salts Bearing Alkanesulfonate Ligands.

An in-depth study of the class of organotin cations bearing weakly coordinating trifluoromethanesulfonate/arylsulfonate has led to key insights into their stability, structural aspects, and role as catalysts. Related chemistry with alkanesulfonate ligands remains a missing link due to the strong Sn-O bond. The study reported herein describes the scope of diorganostannates, [n-Bu4N][R2Sn(OSO2R1)3] (R = n-Bu, R1 = Me(1), Et(2); R = Ph, R1 = Me(3)), as reactive substrates in the presence of adventitious water to afford [n-Bu2SnOH(OSO2Me)] (4), [n-Bu2Sn(H2O)4][n-Bu4N][OSO2Et]3·H2O (5), and [Ph2Sn(H2O)4][n-Bu4N]2[OSO2Me]4 (6), respectively, the latter two being the first examples of salt cocrystals comprising tetra(aqua)diorganotin cations. Hydrolysis of 3 in the presence of 1,4-bis((1H-imidazol-1-yl)methyl)benzene (bix) as the N-donor ligand proceeds via disproportionation and yields [Ph3Sn(bix)](OSO2Me) (7) along with an insoluble solid, likely derived from the hydrolysis of PhSn(OSO2Me)3. Direct evidence of this phenomenon can be gleaned from ESI-MS of 3, which identifies mass clusters corresponding to [Ph3Sn(OSO2Me)2]- and [PhSn(OSO2Me)3-H+]-. X-ray crystallographic studies of 1-7 are reported to establish their structural identity and the role of alkanesulfonate anions in the formation of supramolecular assemblies.

Synthesis and site selective C-H functionalization of imidazo-[1,2-a]pyridines.

Imidazo[1,2-a]pyridine has attracted much interest in drug development because of its potent medicinal properties, therefore the discovery of novel methods for its synthesis and functionalization continues to be an exciting area of research. Although transition metal catalysis has fuelled the most significant developments, extremely beneficial metal-free approaches have also been identified. Even though pertinent reviews focused on imidazo[1,2-a]pyridine synthesis, properties (physicochemical and medicinal), and functionalization at the C3 position have been published, none of these reviews has focused on the outcomes obtained in the field of global ring functionalization. We wish here to describe a brief synthesis and an overview of all the functionalization reactions at each carbon atom, viz, C2, C3, C5, C6, C7 and C8 of this scaffold, divided into sections based on site-selectivity and the type of functionalization methods used.

Living with COPD: understanding patient experiences through the lens of photovoice.

BACKGROUND: Conventional quantitative or qualitative methodologies may not encompass the wide array of experiences of individuals living with Chronic Obstructive Pulmonary Disease (COPD). We used a novel approach - photovoice-to understand the impact of COPD on activities of daily living (ADLs) in a multicultural Asian country. METHODS: We recruited a purposive sample of eight patients from the outpatient clinics of the National University Health System, Singapore, between December 2020 and August 2021. We adopted a photovoice approach for data collection; participants were invited to take photos of how ADLs were impacted by COPD and attend a follow-up interview. An Interpretative Phenomenological Analysis method was used to analyze the data. Data saturation was reached by the seventh patient. RESULTS: COPD and the resulting breathlessness had a profound and diverse impact on our participants' lives. Living with COPD required substantial changes to how everyday tasks are performed, and participants learnt new strategies to deal with such tasks. A mixture of active and passive coping styles was evident. Feelings of frustration, anxiety and a sense of isolation were also reported. Contextual factors impacting ADLs included challenging climatic conditions and the local popularity of traditional or alternative medicine. CONCLUSION: The photovoice technique improved our understanding of the lived experiences of COPD patients and can benefit those who struggle to articulate their views by offering a different way to communicate beyond conventional interviewing.

DeepPlnc: Bi-modal deep learning for highly accurate plant lncRNA discovery.

We present here a bi-modal CNN based deep-learning system, DeepPlnc, to identify plant lncRNAs with high accuracy while using sequence and structural properties. Unlike most of the existing software, it works accurately even in conditions with ambiguity of boundaries and incomplete sequences. It scored consistently high for performance metrics while breaching accuracy of >98% when tested across a large number of validated instances. During multiple benchmarkings DeepPlnc consistently outperformed all the compared tools and maintained a highly significant lead in the range of 2.5%- 4.6% from the second best performing tool (p-value << 0.01). DeepPlnc was used to annotate a de novo assembled transcriptome of a himalayan species where again it suggested its much better suitability for genome and transcriptome annotation purposes than the existing tools. DeepPlnc has been made freely available as a web-server and stand-alone program at https://scbb.ihbt.res.in/DeepPlnc/.

Sustainable solid waste management system using technology-enabled end-of-pipe strategies.

Ever Increasing accumulation of solid waste, attributed to population growth and rapid urbanization, is a serious issue for all nations. This creates hindrance in implementing sustainable solid waste management systems (SWMS), which contribute to socio-economic-environmental-operational (SEEO) benefits for the nations and their citizens. Limited understanding of various solid waste management (SWM) practices, their operational sequence, and other system constraints pose numerous challenges for the concerned authorities and policymakers. This paper provides a framework depicting three broad categories of strategies for managing solid waste: preventive, end-of-pipe (EOP), and environmental restoration. Among these, the research emphasizes on EOP strategies, being suitable alternative as per current requirements, to deal with massive amounts of generated waste. It further adopts Grey-DEMATEL approach to models the causal relationship among EOP strategies to identify the most influential strategy, which influences other ones. The model suggests waste segregation to be the major enabler for other EOP strategies, as it has maximum overall significance value (R + C) between 1.18 and 1.41 and it is the only one with positive value in "net-effect" computation (R-C), compared to other strategies with negative (R-C) values. This would enable concerned authorities to understand and follow the sequence of actions. Finally, a comprehensive framework is proposed for effective, efficient, and sustainable methods of handling different types of solid waste using technology-enabled EOP strategies. A case study is performed to demonstrate the significance of waste segregation towards SEEO benefits. It indicates that technology-based solutions at decentralized depots and establishment of biogas plant in the vicinity of garbage collection point leads to reduction in transportation cost and energy saving in efficient manner. The ground level implementation of our research in an Indian city resulted in the reduction of daily vehicle requirement from 25 to 20 vehicles, leading to approx. 25% savings in overall transportation costs thereby cutting exchequer's bill by up to $ 2820/month. It also reveals that mechanized and decentralized solutions were not effective for inert waste, its disposal to landfill was more suited alternative.

Bimetal-oxide (Fe/Co) modified bagasse-waste carbon coated on lead oxide-battery electrode for metronidazole removal.

Current study covers the preparation and application of a commercial modified lead oxide battery electrode (LBE) in electrochemical oxidation (ECO) of metronidazole (MNZ) in an aqueous phase. Modified electrode is prepared by doping of bimetal-oxide (Fe and Zn) nanoparticles (NPs) & single metal-oxide (Fe/Zn) on bagasse-waste carbon (bwc) which is further coated on LBE. The modified LBE electrode surface was examined for metal-oxide NPs through X-ray diffraction analysis (XRD). Different electrodes are prepared by varying combinations of two metal-oxide based on molar ratio and tested for electrochemical characterization and MNZ removal test. Based on large oxygen evolution potential in a linear sweep volumetry (LSV) analysis and high MNZ removal rate, the best electrode has been represented as Fe1:Co2-bwc/LBE which contains Fe & Co molar ratio of 1:2. Moreover, equilibrium attained at faster rate in degradation process of MNZ, where pseudo first order kinetics of 2.29 × 10-2 min-1 was obtained under optimized condition of (MNZ:100 mg/L, pH:7, CD: 30 mA/cm2 and electrolyte: 0.05 M Na2SO4). Maximum MNZ removal, total organic carbon removal (TOC), mineralization current efficiency (MCE) & energy consumption (EC) of 98.7%, 85.3%, 62.2% & 96.143 kW h/kg-TOC removed are found in 180 min of treatment time for Fe1:Co2-bwc/LBE electrode. Accelerated service life test confirms that the stability of modified electrode is enhanced by 1.5 times compared to pristine LBE. Repeatability test confirms that modified LBE (Fe1:Co2-bwc/LBE) can be utilized up to 3 times.

A Response Surface Model to Predict and Experimentally Tune the Chemical, Magnetic and Optoelectronic Properties of Oxygen-Doped Boron Nitride.

Porous boron nitride (BN), a combination of hexagonal, turbostratic and amorphous BN, has emerged as a new platform photocatalyst. Yet, this material lacks photoactivity under visible light. Theoretical studies predict that tuning the oxygen content in oxygen-doped BN (BNO) could lower the band gap. This is yet to be verified experimentally. We present herein a systematic experimental route to simultaneously tune BNO's chemical, magnetic and optoelectronic properties using a multivariate synthesis parameter space. We report deep visible range band gaps (1.50-2.90 eV) and tuning of the oxygen (2-14 at.%) and specific paramagnetic OB3 contents (7-294 a.u. g-1 ). Through designing a response surface via a design of experiments (DOE) process, we have identified synthesis parameters influencing BNO's chemical, magnetic and optoelectronic properties. We also present model prediction equations relating these properties to the synthesis parameter space that we have validated experimentally. This methodology can help tailor and optimise BN materials for heterogeneous photocatalysis.

Impact of preoperative COVID infection on the outcomes of planned curative-intent cancer surgeries in the second wave of the pandemic from a tertiary care center in India.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic was an unforeseen calamity. Sudden disruption of nonemergency services led to disruption of treatment across all specialties. Oncology revolves around the tenet of timely detection and treatment. Disruption of any sort will jeopardize cure rates. The time interval between coronavirus infection and cancer surgery is variable and needs to be tailored to avoid the progression of the disease. METHODS: We analyzed the impact of preoperative coronavirus disease 2019 (COVID-19) infection on the planned cancer surgery, delay, disease progression, and change of intent of treatment from April 1 to May 31, 2021 at a tertiary care center. All preoperative positive patients were retested after 2 weeks and were considered for surgery if the repeat test was negative and asymptomatic. FINDINGS: Our study included 432 preoperative patients of which 91 (21%) were COVID-19 positive. Amongst this cohort, 76% were operated and the morbidity and mortality were comparable to the COVID-19 negative cohort. Around 10% of the COVID-19 positive were lost to follow up and 10% had disease progression and were deemed palliative INTERPRETATION: SARS-CoV-2 infection has adversely impacted cancer care and a 2-week waiting period postinfection seems to be a safe interval in asymptomatic individuals to consider radical cancer surgery.

Insight into the High Proton Conductivity of One-/Two-Dimensional Cadmium Phosphites.

The study describes the synthesis and structural attributes of two new cadmium phosphites, [Cd{OP(O)(OH)H}2(4,4'-bipy)] (1) and [H2pip][Cd(HPO3)2(H2O)]·H2O (2). The structure of 1 adopts a two-dimensional motif featuring alternate [Cd-µ2-O]2 and [Cd-O-P-O]2-cyclic rings, while the inorganic chains are held together by 4,4'-bipyridine. The presence of strong hydrogen bonding interactions between the appended H2PO3 groups (O---O = 2.55 Å) provides a facile proton conduction pathway and results in a proton conductivity of 3.2 × 10-3 S cm-1 at 75 °C under 77% relative humidity (RH). Compound 2 comprises an anionic framework formed by vertex-shared [Cd-O-P-O]2-cyclic rings, while the [H2pip] cations between the adjacent chains assist a well-directed O-H---O hydrogen-bonded network between coordinated water, lattice water, and phospite groups. The bulk proton conductivity value under conditions as in 1 reaches 4.3 × 10-1 S cm-1. For both 1 and 2, the proton conductivity remains practically unchanged under ambient temperatures (25-35 °C), suggesting their potential in low-temperature fuel cells.

Synthesis of 3-N-/O-/S-methyl-imidazo[1,2-a] pyridine derivatives for caspase-3 mediated apoptosis induced anticancer activity.

A library of 49 analogs of imidazo[1,2-a]pyridine with 2-halo, aryl, styryl and phenylethynyl-substitution at C-2 position and N-/O-/S-methyl linkage at C-3 position, have been synthesized and evaluated for their anti-proliferative activity against breast (MCF-7, MDA-MB-231), pancreatic (MiaPaca-2), lung (A549), prostate (PC-3) and colon (HCT-116) cancer cell lines and normal cells (HEK-293). Among the screened compounds, 5b exhibited best anticancer potential in all tested cancer cells with IC50 ranging from 3.5 to 61.1 µM and no toxicity in normal cells. Further, mechanistic study of 5b revealed concentration dependent increased generation of ROS, reduced mitochondrial membrane potential (MMP), surface and nuclear morphological alterations and inhibition of colony formation in HCT-116 cells. Western blot results had shown that the cell death in HCT-116 colon cancer cells was achieved through the induction of apoptosis via upregulation of the PTEN gene and downregulation of AKT pathway. Similarly, 5b treatment induced caspase-3 cleavage which is a hallmark of apoptosis. Molecular docking and binding energy (ΔG) studies of hit 5b with respect to three important cancer targets (EGFR, mTOR and PI3Kα) revealed strong binding of inhibitor with PI3Kα (docking score -6.932 and ΔG -56.297).

Cancer care continuum at a tertiary care centre in India during the Covid-19 pandemic and nationwide lockdown: Healthcare delivery through telemedicine.

Background The Covid-19 pandemic and subsequent lockdown in India caused disruptions in cancer treatment due to the restriction on movement of patients. We aimed to maintain continuity in cancer treatment during the lockdown through teleconsultations. We tried to reach out to our patients using telephonic consultations by establishing a Teleconsult Centre facility run by a team of doctors and patient navigators. Methods We telephonically contacted all patients who had outpatient appointments from 23 March to 30 April 2020 at our centre through the Teleconsult Centre to understand their current circumstances, feasibility of follow-up, local resources and offered best possible alternatives to continue cancer treatment, if required. Results Of the 2686 patients scheduled for follow-up during this period, we could contact 1783 patients in 9 working days. Through teleconsultations, we could defer follow-ups of 1034 patients (57.99%, 95% confidence interval [CI] 55.6%-60.3%), thus reducing the need for patients to travel to the hospital. Change in systemic therapy was made in 75 patients (4.2%, 95% CI 3.3%-5.2%) as per the requirements and available resources. Symptoms suggestive of disease progression were picked up in 12 patients (0.67%, 95% CI 0.35%-1.17%), who were advised to meet local physicians. Conclusion Our study suggests that the majority of patients on follow-up can be managed with teleconsultation in times of crisis. Teleconsultation has the potential of being one of the standard methods of patient follow-up even during periods of normalcy.

In-depth assembly of organ and development dissected Picrorhiza kurroa proteome map using mass spectrometry.

BACKGROUND: Picrorhiza kurroa Royle ex Benth. being a rich source of phytochemicals, is a promising high altitude medicinal herb of Himalaya. The medicinal potential is attributed to picrosides i.e. iridoid glycosides, which synthesized in organ-specific manner through highly complex pathways. Here, we present a large-scale proteome reference map of P. kurroa, consisting of four morphologically differentiated organs and two developmental stages. RESULTS: We were able to identify 5186 protein accessions (FDR < 1%) providing a deep coverage of protein abundance array, spanning around six orders of magnitude. Most of the identified proteins are associated with metabolic processes, response to abiotic stimuli and cellular processes. Organ specific sub-proteomes highlights organ specialized functions that would offer insights to explore tissue profile for specific protein classes. With reference to P. kurroa development, vegetative phase is enriched with growth related processes, however generative phase harvests more energy in secondary metabolic pathways. Furthermore, stress-responsive proteins, RNA binding proteins (RBPs) and post-translational modifications (PTMs), particularly phosphorylation and ADP-ribosylation play an important role in P. kurroa adaptation to alpine environment. The proteins involved in the synthesis of secondary metabolites are well represented in P. kurroa proteome. The phytochemical analysis revealed that marker compounds were highly accumulated in rhizome and overall, during the late stage of development. CONCLUSIONS: This report represents first extensive proteomic description of organ and developmental dissected P. kurroa, providing a platform for future studies related to stress tolerance and medical applications.

Studies on the Genesis and Proton Conductivity of Imidazole-Based Linear and Open-Framework Zinc Phosphites.

Three new zinc phosphites, [HIm]2[Zn3(HPO3)4] (1), [Zn2(HPO3)2Im2] (2), and [Zn(HPO3)Im] (3) (Im = imidazole), have been synthesized from the hydro/solvothermal reaction of zinc acetate, dimethyl phosphite, and imidazole by varying the temperature and solvent of the reaction medium. The structure of 1 is built from vertex-sharing of four HPO3-capped Zn3P3 units and adopts an open framework with 12-ring channels stabilized by HIm cations via N-H···O hydrogen bonds. For 2, the inorganic skeleton is comprised of alternating ZnO4 and HPO3 tetrahedra, while the coordinatively associated ZnN2O2 fragments occupy the 12-ring hexagonal channels. Compound 3 adopts a ladder-type one-dimensional structure and exhibits N-H···O hydrogen-bonding interactions to afford a supramolecular assembly. A plausible rationale on the genesis of 1-3 has been put forth by reacting the preformed inorganic zinc phosphites Zn{OP(O)(OMe)H}2 or [Zn2(HPO3)2(H2O)4]·H2O with imidazole as the structure-directing ligand. Alternating-current impedance measurements reveal that 1 and 3 exhibit proton conductivities on the order of 10-3-10-4 S cm-1 between 25 and 100 °C under 35 and 77% relative humidity in repeated impedance cycles (Ea = 0.22-0.35 eV). On the contrary, the conduction property is completely impaired in 2 under similar conditions.

Palladium(II) catalyzed site-selective C-H olefination of imidazo[1,2-a]pyridines.

Herein, we disclose an efficient Pd(II)-catalyzed site selective C8 alkenylation of imidazo[1,2-a]pyridines with electronically biased olefinic substrates. Notably, besides the presence of four C-H sites available, selective mono-alkenylation was achieved by N-chelation overriding O-chelation. The versatility and scalability of the catalysis enabled the selective late-stage functionalization of a marketed drug, zolimidine. Various substituted heteroaryl alkenes can be afforded with moderate to good yields with high C8 regioselectivity.

Taking on a pandemic's challenge: Emergent solutions from a single Hemophlia treatment center in North India.

INTRODUCTION: The global pandemic caused by SARS-COV-2 infection has raised several unique concerns in the bleeding disorders community. Although the risk of COVID-19 infection is not increased in patients with inherited bleeding disorders, the indirect effects of this infection are many. METHODS: A cross sectional survey was conducted among patients registered to our centre with inherited bleeding disorders. A web-based based questionnaire was developed and shared with patients and families. RESULTS: 120 patients/ families answered the questionnaire completely. During the period of lockdown, many had bleeds that were left untreated due to either difficulty in travel or unavailability of treatment. The time to treatment ranged from 8 h to 15 days in those who had a bleed. 36 % faced financial difficulties and 40 % families reported losing their job or source of income during this period. DISCUSSION: Few solutions that emerged while treating patients during this period and recommendations are discussed. Even though haemophilia has been included under the essential health services and states mandated to continue treatment for these patients despite the global crisis, patients still face challenges in terms of transport and finance.