Publications by authors named "Sandeep Kumar"

1,135 Publications

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Telemedicine trends in orthopaedics and trauma during the COVID-19 pandemic: A bibliometric analysis and review.

J Taibah Univ Med Sci 2021 Oct 18. Epub 2021 Oct 18.

Department of Orthopaedics, Hamdard Institute of Medical Sciences and Research, New Delhi, India.

Objectives: In the wake of recent widespread interest in telemedicine during the COVID-19 era, many orthopaedic surgeons may be unfamiliar with clinical examination skills, patients' safety, data security, and implementation-related concerns in telemedicine. We present a bibliometric analysis and review of the telemedicine-related publications concerning orthopaedics care during the COVID-19 pandemic. Such analysis can help orthopaedic surgeons become acquainted with the recent developments in telemedicine and its usage in regular orthopaedics practice.

Methods: We systematically searched the database of Thomson Reuters Web of Science for telemedicine-related articles in orthopaedics published during the COVID-19 pandemic. The selected articles were analysed for their source journals, corresponding authors, investigating institutions, countries of the corresponding authors, number of citations, study types, levels of evidence, and a qualitative review.

Results: Fifty-nine articles meeting the inclusion criteria were published in 28 journals. Three hundred forty-two authors contributed to these research papers. The United States (US) contributed the most number of articles to the telemedicine-related orthopaedics research during the COVID-19 era. All articles combined had a total of 383 citations and 66.1% were related to the Economic and Decision-making Analyses of telemedicine implementation. By and large, level IV evidence was predominant in our review.

Conclusion: Telemedicine can satisfactorily cover a major proportion of patients' visits to outpatient departments, thus limiting hospitals' physical workload. Telemedicine has a potential future role in emergency orthopaedics and inpatient care through virtual aids. The issues related to patient privacy, data security, medicolegal, and reimbursement-related aspects need to be addressed through precise national or regional guidelines. Lastly, the orthopaedic physical examination is a weak link in telemedicine and needs to be strengthened.
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http://dx.doi.org/10.1016/j.jtumed.2021.09.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8521392PMC
October 2021

Metastatic cluster 2-related pheochromocytoma/paraganglioma: a single-center experience and systematic review.

Endocr Connect 2021 Oct 1. Epub 2021 Oct 1.

T Bandgar, Department of Endocrinology, Seth GS Medical College and KEM Hospital, Mumbai, India.

Objective: Risk of metastatic disease in the cluster 2-related pheochromocytoma/paraganglioma (PPGL) is low. In MEN2 patients, identification of origin of metastases from pheochromocytoma (PCC) or medullary thyroid carcinoma (MTC) is challenging as both are of neuroendocrine origin. We aim to describe our experience and perform a systematic review to assess prevalence, demographics, biochemistry, diagnostic evaluation, management and predictors of cluster 2-related metastatic PPGL.

Design: Retrospective study with systematic review of literature.

Methods: Data of 3 cases from our cohort and 43 cases from world literature were analyzed. For calculation of prevalence, all reported patients (n=3063) of cluster 2 were included.

Results: The risk of metastasis in cluster 2-related PPGL was 2.6% (2% in RET, 5% in NF1, 4.8% in TMEM127 and 16.7% in MAX variation). In metastatic PCC in MEN2, median age was 39 years, bilateral tumors were present in 71% and median tumor size was 9.7 cm (range 4-19) with 43.5% mortality. All patients had primary tumor size ≥4cm. Origin of primary was diagnosed by histopathology of metastatic lesion in 11(57.9%), 131I-MIBG scan in 6(31.6%), and selective venous sampling and computed tomography in one (5.3%) each. In subgroup of NF1, median age was 46 years (range 14-59) with median tumor size 6cm and 57% mortality.

Conclusion: The risk of metastatic disease in cluster 2-related PPGL is 2.6%, being especially high in tumors with size ≥4cm and is associated with high mortality. One-third patients of NF1 with metastatic PPGL had presented in 2nd decade of life. Long-term studies are needed to formulate management recommendations.
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http://dx.doi.org/10.1530/EC-21-0455DOI Listing
October 2021

Isolation of Endothelial Cells from the Lumen of Mouse Carotid Arteries for Single-cell Multi-omics Experiments.

J Vis Exp 2021 10 4(176). Epub 2021 Oct 4.

Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University; Division of Cardiology, Georgia Institute of Technology and Emory University;

Atherosclerosis is an inflammatory disease of the arterial regions exposed to disturbed blood flow (d-flow). D-flow regulates the expression of genes in the endothelium at the transcriptomic and epigenomic levels, resulting in proatherogenic responses. Recently, single-cell RNA sequencing (scRNAseq) and single-cell Assay for Transposase Accessible Chromatin sequencing (scATACseq) studies were performed to determine the transcriptomic and chromatin accessibility changes at a single-cell resolution using the mouse partial carotid ligation (PCL) model. As endothelial cells (ECs) represent a minor fraction of the total cell populations in the artery wall, a luminal digestion method was used to obtain EC-enriched single-cell preparations. For this study, mice were subjected to PCL surgery to induce d-flow in the left carotid artery (LCA) while using the right carotid artery (RCA) as a control. The carotid arteries were dissected out two days or two weeks post PCL surgery. The lumen of each carotid was subjected to collagenase digestion, and endothelial-enriched single cells or single nuclei were obtained. These single-cell and single-nuclei preparations were subsequently barcoded using a 10x Genomics microfluidic setup. The barcoded single-cells and single-nuclei were then utilized for RNA preparation, library generation, and sequencing on a high-throughput DNA sequencer. Post bioinformatics processing, the scRNAseq and scATACseq datasets identified various cell types from the luminal digestion, primarily consisting of ECs. Smooth muscle cells, fibroblasts, and immune cells were also present. This EC-enrichment method aided in understanding the effect of blood flow on the endothelium, which could have been difficult with the total artery digestion method. The EC-enriched single-cell preparation method can be used to perform single-cell omics studies in EC-knockouts and transgenic mice where the effect of blood flow on these genes has not been studied. Importantly, this technique can be adapted to isolate EC-enriched single cells from human artery explants to perform similar mechanistic studies.
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http://dx.doi.org/10.3791/63128DOI Listing
October 2021

NMR-Based Metabolomics Revealed the Underlying Inflammatory Pathology in Reactive Arthritis Synovial Joints.

J Proteome Res 2021 Oct 18. Epub 2021 Oct 18.

Centre of Biomedical Research, Lucknow 226014, India.

Reactive arthritis (ReA) is an aseptic synovitis condition that often develops 2-4 weeks after a distant (extra-articular) infection with , , , , and species. The metabolic changes in the synovial fluid (SF) may serve as indicative markers to both improve the diagnostic accuracy and understand the underlying inflammatory pathology of ReA. With this aim, the metabolic profiles of SF collected from ReA ( = 58) and non-ReA, i.e., rheumatoid arthritis (RA, = 21) and osteoarthritis (OA, = 20) patients, respectively, were measured using NMR spectroscopy and compared using orthogonal partial least-squares discriminant analysis (OPLS-DA). The discriminatory metabolic features were further evaluated for their diagnostic potential using the receiver operating characteristic (ROC) curve analysis. Compared to RA, two (alanine and carnitine), and compared to OA, six (NAG, glutamate, glycerol, isoleucine, alanine, and glucose) metabolic features were identified as diagnostic biomarkers. We further demonstrated the impact of ReA synovitis condition on the serum metabolic profiles through performing a correlation analysis. The Pearson rank coefficient () was estimated for 38 metabolites (profiled in both SF and serum samples obtained in pair from ReA patients) and was found significantly positive for 71% of the metabolites ( ranging from 0.17 to 0.87).
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http://dx.doi.org/10.1021/acs.jproteome.1c00620DOI Listing
October 2021

Aberrant Promoter Hypermethylation of and Genes in Colorectal Cancer - Significance in Young Patients.

Indian J Surg Oncol 2021 Sep 24;12(3):454-459. Epub 2021 Apr 24.

Department of Biochemistry, Kidwai Memorial Institute of Oncology, Bengaluru, Karnataka 560029 India.

Objective: The clinical profile of colorectal cancers (CRC) in India is different from that described in western countries. Microsatellite instability and APC mutation explain the molecular biology of up to 50% of colorectal cancers. Global genome hypermethylation may be the cause in at least 20% of cases. Few studies from India have examined the epigenetic profile of colorectal cancers. This study was designed to study aberrant promoter hypermethylation of two select tumour suppressor genes () in patients with colorectal cancer and their association with clinicopathologic features.

Methods: A total of 41 samples including controls were collected from colorectal cancer patients. DNA was isolated from tumour tissue, and methylation-specific PCR was performed for the 2 genes.

Results: and promoter hypermethylation was found in 26% and 48% of CRC cases, respectively. promoter hypermethylation was more often seen in young CRC patients aged 40 years or less, and this was found to be statistically significant ( value = 0.037).

Conclusion: hypermethylation is peculiar to rectal cancers and left-sided colonic tumours in young patients. Large-scale population-based studies with extensive genetic and epigenetic characterization are required for a better understanding and further validation of our findings. For individuals diagnosed with sporadic CRC, these studies on specimen might help predict prognosis and response to therapy.
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http://dx.doi.org/10.1007/s13193-021-01325-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8490567PMC
September 2021

Characterization of Differentially Expressed miRNAs by CXCL12/SDF-1 in Human Bone Marrow Stromal Cells.

Biomol Concepts 2021 Oct 13;12(1):132-143. Epub 2021 Oct 13.

Department of Orthopedics, Augusta University, Augusta, GA.

Stromal cell-derived factor 1 (SDF-1) is known to influence bone marrow stromal cell (BMSC) migration, osteogenic differentiation, and fracture healing. We hypothesize that SDF-1 mediates some of its effects on BMSCs through epigenetic regulation, specifically via microRNAs (miRNAs). MiRNAs are small non-coding RNAs that target specific mRNA and prevent their translation. We performed global miRNA analysis and determined several miRNAs were differentially expressed in response to SDF-1 treatment. Gene Expression Omnibus (GEO) dataset analysis showed that these miRNAs play an important role in osteogenic differentiation and fracture healing. KEGG and GO analysis indicated that SDF-1 dependent miRNAs changes affect multiple cellular pathways, including fatty acid biosynthesis, thyroid hormone signaling, and mucin-type O-glycan biosynthesis pathways. Furthermore, bioinformatics analysis showed several miRNAs target genes related to stem cell migration and differentiation. This study's findings indicated that SDF-1 induces some of its effects on BMSCs function through miRNA regulation.
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http://dx.doi.org/10.1515/bmc-2021-0015DOI Listing
October 2021

Optical damage limit of efficient spintronic THz emitters.

iScience 2021 Oct 21;24(10):103152. Epub 2021 Sep 21.

Femtosecond Spectroscopy and Nonlinear Photonics Laboratory, Department of Physics, Indian Institute of Technology Delhi, New Delhi 110016, India.

THz pulses are generated from femtosecond pulse-excited ferromagnetic/nonmagnetic spintronic heterostructures via inverse spin Hall effect. The highest possible THz signal strength from spintronic THz emitters is limited by the optical damage threshold of the corresponding heterostructures at the excitation wavelength. For the thickness-optimized spintronic heterostructure, the THz generation efficiency does not saturate with the excitation fluence even up till the damage threshold. Bilayer (Fe, CoFeB)/(Pt, Ta)-based ferromagnetic/nonmagnetic (FM/NM) spintronic heterostructures have been studied for an optimized performance for THz generation when pumped by sub-50 fs amplified laser pulses at 800 nm. Among them, CoFeB/Pt is the best combination for an efficient THz source. The optimized FM/NM spintronic heterostructure having α-phase Ta as the nonmagnetic layer shows the highest damage threshold as compared to those with Pt, irrespective of their generation efficiency. The damage threshold of the Fe/Ta heterostructure on a quartz substrate is ∼85 GW/cm.
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http://dx.doi.org/10.1016/j.isci.2021.103152DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8496183PMC
October 2021

High sodium ionic conductivity in PEO/PVP solid polymer electrolytes with InAs nanowire fillers.

Sci Rep 2021 Oct 12;11(1):20180. Epub 2021 Oct 12.

Department of Physics, Central University of Rajasthan, Ajmer, 305817, India.

Solid-state sodium ion batteries are frequently referred to as the most promising technology for next-generation energy storage applications. However, developing a suitable solid electrolyte with high ionic conductivity, excellent electrolyte-electrode interfaces, and a wide electrochemical stability window, remains a major challenge. Although solid-polymer electrolytes have attracted great interest due to their low cost, low density and very good processability, they generally have significantly lower ionic conductivity and poor mechanical strength. Here, we report on the development of a low-cost composite solid polymer electrolyte comprised of poly(ethylene oxide), poly(vinylpyrrolidone) and sodium hexafluorophosphate, mixed with indium arsenide nanowires. We show that the addition of 1.0% by weight of indium arsenide nanowires increases the sodium ion conductivity in the polymer to 1.50 × 10 Scm at 40 °C. In order to explain this remarkable characteristic, we propose a new transport model in which sodium ions hop between close-spaced defect sites present on the surface of the nanowires, forming an effective complex conductive percolation network. Our work represents a significant advance in the development of novel solid polymer electrolytes with embedded engineered ultrafast 1D percolation networks for near-future generations of low-cost, high-performance batteries with excellent energy storage capabilities.
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http://dx.doi.org/10.1038/s41598-021-99663-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8511152PMC
October 2021

Frequency of osteoarthritis and functional outcome of operated tibial plateau fractures: A minimum of 5 years follow up.

J Pak Med Assoc 2021 Aug;71(Suppl 5)(8):S8-S12

Department of Orthopaedics, Jinnah Postgraduate Medical Centre, Karachi, Pakistan.

Objective: Tibial plateau is an important weight bearing surface and its fractures are the result of axial compressive forces. Post-traumatic osteoarthritis (PTOA) occurs despite anatomical joint reconstruction. In this study we determined the incidence of PTOA after primary management of tibial plateau fractures and determined the risk factors of PTOA of patients whose results were published at 24 months and now we present a five year follow up of the same patients.

Methods: In this study, we presented the prospective data of 109 patients who were managed for tibial plateau fractures, from August 2009 to June 2018 a Jinnah postgraduate medical centre. Data of patients regarding clinical and radiological, functional outcome (according to the American Knee Society criteria), post-procedural visual analogue scale (VAS) pain score was included. Incidence of development of PTOA was noted in each patient using the Ahlbäck classification.

Results: Out of 109 patients with tibial plateau fractures, 81 (74.3%) were male and 28 (25.7%) were female. Mean time lag from injury to surgery was 10.14±9.07 days. Overall incidence of osteoarthritis was 50 (45.9%). Advanced age >50 years (odds ratio 9.1 (3.7-22.1), p-value <0.0001), female gender (odds ratio; 3.40 (1.36-8.46), p-value 0.007), VAS score >4 ((odds ratio; 73.28 (15.7-341.5), p-value <0.001)), Articular depression (odds ratio; 35.25 (11.49-108.1), p-value <0.001) and degree of mal-alignment (odds ratio; 25.72 (9.30-71.12), p-value <0.001) were found to be the risk factors of PTOA. While excellent functional outcomes were protective for PTOA (odds ratio; 4.8, p-value <0.001). Thirty out of fifty patients (60%) suffering from secondary arthritis of the knee required knee replacement (TKR). Twenty-one patients (70%) were males that underwent TKR.

Conclusions: There is a high proportion of osteoarthritis following tibial plateau fixation. The risk factors that related to the development of secondary arthritis our cohorts were increased age, male gender, a decrease in AKSS and a higher VAS group. Knee arthroplasty is the only option for our cohorts with severe posttraumatic arthritis.
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August 2021

Coagulation factor IX gene transfer to non-human primates using engineered AAV3 capsid and hepatic optimized expression cassette.

Mol Ther Methods Clin Dev 2021 Dec 26;23:98-107. Epub 2021 Aug 26.

Department of Pediatrics, Herman B Wells Center for Pediatric Research, Indiana University, Indianapolis, IN, USA.

Hepatic gene transfer with adeno-associated viral (AAV) vectors shows much promise for the treatment of the X-linked bleeding disorder hemophilia B in multiple clinical trials. In an effort to further innovate this approach and to introduce alternative vector designs with potentially superior features into clinical development, we recently built a vector platform based on AAV serotype 3 because of its superior tropism for human hepatocytes. A vector genome with serotype-matched inverted terminal repeats expressing hyperactive human coagulation factor IX (FIX)-Padua was designed for clinical use that is optimized for translation using hepatocyte-specific codon-usage bias and is depleted of immune stimulatory CpG motifs. Here, this vector genome was packaged into AAV3 (T492V + S663V) capsid for hepatic gene transfer in non-human primates. FIX activity within or near the normal range was obtained at a low vector dose of 5 × 10 vector genomes/kg. Pre-existing neutralizing antibodies, however, completely or partially blocked hepatic gene transfer at that dose. No CD8 T cell response against capsid was observed. Antibodies against the human FIX transgene product formed at a 10-fold higher vector dose, albeit hepatic gene transfer was remarkably consistent, and sustained FIX activity in the normal range was nonetheless achieved in two of three animals for the 3-month duration of the study. These results support the use of this vector at low vector doses for gene therapy of hemophilia B in humans.
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http://dx.doi.org/10.1016/j.omtm.2021.08.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8476648PMC
December 2021

EEG Signal Feature Selection Algorithm and Support Vector Machine Model in Patient's Fatigue Recognition.

Arab J Sci Eng 2021 Oct 5:1-7. Epub 2021 Oct 5.

Department of Electronics and Communication Engineering, SR University, Warangal, India.

In March 2020, a cohort of 26 is treated critically ill hospitalized SARS-CoV-2 infected patients who received EEGs to assess unexplained altered mental status, loss of consciousness, or poor arousal and responsiveness. The objective of the present work is to develop a method that is able to automatically determine mental status of vigilance, i.e., a person's state of alertness. Such a task is relevant to diverse domains, where a person is expected or required to be in a particular state of mind. Aiming at the EEG feature selection and classification model in the identification of fatigue driving, the discretization algorithm using rough set theory is proposed to select the channel and EEG signal feature quantities. The support vector machine (SVM) is selected as the fatigue driving recognition model, and the risk of fatigue misjudgment is taken as SVM model parameters for model optimization. The experimental results of subjects show that compared with the principal component method, the rough set discretization algorithm selects fewer features, and the compatibility threshold 0.8. The number of features selected among the candidate features is 208. The features selected by different subjects are different and have an impact on the establishment of the support vector machine recognition model. Fatigue misjudgment risk control parameters can adjust the support vector machine recognition model error judgment risk. Even if the present approach is costly in computation time, it allows constructing a decision rule that provides an accurate and fast prediction of the alertness state of an unseen individual.
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http://dx.doi.org/10.1007/s13369-021-06206-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8490845PMC
October 2021

A 3-Dimensional Coculture Model to Visualize and Monitor Interaction Between Pancreatic Cancer and Islet β Cells.

Pancreas 2021 Aug;50(7):982-989

Centre for Cancer Biomarkers and Biotherapeutics, Barts Cancer Institute, Queen Mary University of London, London.

Objectives: To facilitate exploring a link between pancreatic ductal adenocarcinoma (PDAC) and diabetes mellitus, we constructed a novel 3-dimensional (3D) in vitro coculturing system for studying interactions between PDAC and islet cells.

Methods: Adopting a 3D rotary cell culture system, we have cocultured several PDAC cell lines and MIN6 islet β cells. The cellular morphology and viability of both cell types were investigated by time-lapse imaging, confocal and scanning electron microscopy, and immunohistochemistry.

Results: The developed coculture method enabled the formation of 3D PDAC and β-cell spheroids (pseudo islets). We showed that surface morphology and growth of cultured cells mimicked their in vivo appearance. In addition, the coculture demonstrated the affinity of the PDAC cells to grow around and invade the pseudo islets.

Conclusions: Using rotary cell culture system, we have established a simple in vitro 3D pancreatic model. It is a flexible culture system that can easily be expanded with the addition of various stromal/neural components to further mimic in vivo conditions, thus enabling holistic investigation of the endocrine and exocrine pancreas.
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http://dx.doi.org/10.1097/MPA.0000000000001865DOI Listing
August 2021

Tryptophan-Kynurenine Pathway in COVID-19-Dependent Musculoskeletal Pathology: A Minireview.

Mediators Inflamm 2021 5;2021:2911578. Epub 2021 Oct 5.

Department of Cell Biology and Anatomy, Augusta University, Augusta, GA, USA.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes coronavirus disease 2019 (COVID-19), affecting multiple organ systems, including the respiratory tract and lungs. Several studies have reported that the tryptophan-kynurenine pathway is altered in COVID-19 patients. The tryptophan-kynurenine pathway plays a vital role in regulating inflammation, metabolism, immune responses, and musculoskeletal system biology. In this minireview, we surmise the effects of the kynurenine pathway in COVID-19 patients and how this pathway might impact muscle and bone biology.
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http://dx.doi.org/10.1155/2021/2911578DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8492288PMC
October 2021

Responses of leached nitrogen concentrations and soil health to winter rye cover crop under no-till corn-soybean rotation in the Northern Great Plains.

J Environ Qual 2021 Oct 5. Epub 2021 Oct 5.

Department of Agronomy, Horticulture and Plant Science, South Dakota State University, Brookings, SD, 57007, USA.

Winter rye (Secale cereale L.) is an important cover crop (CC) in the Northern Great Plains (NGP); yet concerns over its establishment under variable weather conditions of this region is an important limitation for its widespread adoption. This study evaluates the impacts of no-till corn (Zea mays L.)-soybean (Glycine max L.) rotation with winter rye CC established in 2017 on 1) water quality (nitrate-N, NO -N; ammonia-N, NH -N; and total nitrogen, TN); and 2) soil health parameters at 0-15 cm depth. Data showed that rye CC biomass was 251 kg ha in 2018, 1213 kg ha in 2019, and 147 kg ha in 2020, coinciding with contrasting growing degree days for rye CC i.e., 1458, 2042, 794, respectively, as a consequence of variable weather conditions. Water quality was not affected for the periods where rye growth was <300 kg ha . In the season where rye CC had greater biomass (1213 kg ha ), significant reductions in leached NO -N (19-20%) and TN (8.5-16%) concentrations were observed, due to greater N uptake by rye CC (18.8 kg N ha ). Rye CC showed significantly (p≤0.05) higher microbially active carbon (MAC, ∼13%) and water-extractable organic nitrogen (WEON, ∼11%) than control treatment. Non-significant impacts on soil health indicators due to rye CC showed that study duration (3 years) may not be sufficient to see the beneficial impacts of cover crops on soils. However, significant reductions in leached NO -N and TN concentrations for one (2019) out of three study years suggest that rye with optimal growth has the potential of reducing nitrogen leaching and enhancing soil health for the NGP region. This article is protected by copyright. All rights reserved.
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http://dx.doi.org/10.1002/jeq2.20294DOI Listing
October 2021

Conventional fluoroscopic views are inadequate to predict the Tip Apex Distance and articular clearance of sliding screw devices: A computed tomography-based analysis.

Injury 2021 Sep 23. Epub 2021 Sep 23.

Department of Orthopaedics, Hamdard Institute of Medical Sciences and Research, New Delhi, IN, India. Electronic address:

Introduction: Tip-apex-distance (TAD) has been widely advocated as the index to predict the risk of screw cut out in hip fractures treated with sliding hip screw devices. The fluoroscopic extents of the femoral head can change with the slightest change in the limb position which includes internal and external rotations, adduction and abduction. These changes can affect the visible TAD and articular-clearance of the screw-tip. The purpose of this Computed-tomography(CT) based analysis is to analyze the variations of the radiographically visible articular-clearance and TAD measurements with limb positioning and to determine the appropriate fluoroscopic projections for different screw-positions within the femoral head.

Material And Methods: We retrospectively analysed CT studies of twenty healthy proximal femora. Spatial markers simulating screw tips were placed in the different combinations of anteroposterior(AP) and cephalocaudal(CC) positions. Software-based AP and lateral radiographs were developed for each screw position. Additional AP radiographs with femur in internal and external rotation, and lateral radiographs with the femur in adduction and abduction were developed. The variation of TAD and articular-clearance of the screw was measured among these radiographs for individual screw tip positions.

Results: Screw tip placed centrally in AP and CC planes position didn't show any significant variation in TAD and articular-clearance with modified AP and lateral radiographs. Significant differences were observed in TAD and articular-clearance values for other screw tip positions. Anteriorly placed screw tips had higher TAD and articular-clearance values with external rotation and similar changes were observed with posteriorly placed tips in internal rotation. Inferiorly placed tips had higher articular-clearance and TAD with limb abduction and similar changes were observed for superiorly placed tips with limb adduction.

Conclusions: For the sliding screws placed in non-central locations, the clearance of the screw tip from the articular margins can not be appropriately estimated with conventional AP and lateral views. Additional views with the limb in internal rotation and external rotation in AP view, and adduction-abduction in lateral view are required to safely place the sliding screw in the femoral head. The limb should be brought to a neutral alignment for the accurate estimation of TAD.
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http://dx.doi.org/10.1016/j.injury.2021.09.033DOI Listing
September 2021

Translation and Psychometric Validation of Belief about Medication Questionnaire in Parents of Children with Difficult-to-Treat Nephrotic Syndrome.

Indian J Pediatr 2021 Sep 30. Epub 2021 Sep 30.

Department of Pediatrics, LHMC and Kalawati Saran Children's Hospital, New Delhi, India.

Belief about Medications Questionnaire (BMQ) is a validated tool to assess the beliefs of patients about their medications. The objective was to translate the BMQ in Hindi, and to perform reliability and validity testing of Hindi version in Indian children (aged ≤ 12 y) with difficult-to-treat nephrotic syndrome (DTNS). The BMQ was first translated using the standard translation and back-translation procedure. The BMQ-Hindi was then applied to 110 children with DTNS. The Principal component analysis was performed, and Cronbach alpha (CA) was calculated. Construct validity was tested by assessing the correlation (Pearson r) between BMQ-Hindi scores and Reported Adherence to Medication (RAM-Hindi) scale. The BMQHindi displayed two-factorial (five-item each) structure similar to BMQ-English. The CA was 0.79 and 0.63 for 'necessity' and 'concerns' subscale, respectively and was comparable to BMQ-English. BMQ-Hindi is a valid and reliable tool for Indian children with DTNS to assess parental beliefs about their child's medications.
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http://dx.doi.org/10.1007/s12098-021-03907-1DOI Listing
September 2021

Alteration in Nasopharyngeal Microbiota Profile in Aged Patients with COVID-19.

Diagnostics (Basel) 2021 Sep 5;11(9). Epub 2021 Sep 5.

Department of Cellular Biology and Anatomy, Augusta University, Augusta, GA 30912, USA.

Severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2) is an infectious virus that causes coronavirus disease 2019 (COVID-19) transmitted mainly through droplets and aerosol affecting the respiratory tract and lungs. Little is known regarding why some individuals are more susceptible than others and develop severe symptoms. In this study, we analyzed the nasopharyngeal microbiota profile of aged patients with COVID-19 (asymptomatic vs. symptomatic) vs. healthy individuals. We examined the nasopharynx swab of 84 aged-matched patients, out of which 27 were negative asymptomatic (NegA), 30 were positive asymptomatic (PA), and 27 patients were positive symptomatic (PSY). Our analysis revealed the presence of abundant Cyanobacterial taxa at phylum level in PA (-value = 0.0016) and PSY (-value = 0.00038) patients along with an upward trend in the population of Litoricola, Amylibacter, Balneola, and Aeromonas at the genus level. Furthermore, to know the relationship between the nasal microbiota composition and severity of COVID-19, we compared PA and PSY groups. Our data show that the nasal microbiota of PSY patients was significantly enriched with the signatures of two bacterial taxa: Cutibacterium (-value = 0.045) and Lentimonas (-value = 0.007. Furthermore, we also found a significantly lower abundance of five bacterial taxa, namely: Prevotellaceae (-value = 7 × 10), Luminiphilus (-value = 0.027), Flectobacillus (-value = 0.027), Comamonas (-value = 0.048), and Jannaschia (-value = 0.012) in PSY patients. The dysbiosis of the nasal microbiota in COVID-19 positive patients might have a role in contributing to the severity of COVID-19. The findings of our study show that there is a strong correlation between the composition of the nasal microbiota and COVID-19 severity. Further studies are needed to validate our finding in large-scale samples and to correlate immune response (cytokine Strome) and nasal microbiota to identify underlying mechanisms and develop therapeutic strategies against COVID-19.
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http://dx.doi.org/10.3390/diagnostics11091622DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8467337PMC
September 2021

Assessment of the Relationship between Oral Health Behavior, Oral Hygiene, and Gingival Status of Adolescent Tobacco Consumers in Ranchi, Jharkhand: A Comparative Study.

Adv Prev Med 2021 9;2021:3548132. Epub 2021 Sep 9.

Department of Oral Medicine and Radiology, Saraswati Dental College, Lucknow 227105, India.

Background: Tobacco consumption is very prevalent in India and associated with a number of oral health problems. Good oral health behavior plays a significant role in improving oral hygiene status.

Objectives: To assess the relationship between the oral health behavior, oral hygiene, and gingival status of adolescent tobacco consumers (smoke/smokeless form) and to compare it with that of the nonconsumers of tobacco in the same age group, who were selected from the OPD of Dental Institute, RIMS.

Methods: This was a cross-sectional study carried out in Ranchi. The study included a total of 400 adolescents who were reported to be consumers of tobacco and 400 adolescents who were nonconsumers of tobacco. The oral health behavior was assessed using HU-DBI. The plaque and gingival scores were assessed using standardized indices. Data were analyzed using the Chi-square test, independent sample -test, and Pearson's correlation. The significance level was set at ≤ 0.05.

Results: The majority of tobacco consumers were found to have poor plaque scores as assessed using the plaque index. As assessed by the gingival index, the majority of the tobacco consumers were found to have a severe form of gingivitis. The mean plaque score (2.38 ± 0.51, value <0.001) and the mean gingival score (2.6 ± 0.63, value <0.001) were significantly higher in tobacco consumers. The mean HU-DBI score was significantly higher in non-tobacco consumers (8.3 ± 1.60, value <0.001). It was observed that the gingival and plaque scores have a significant negative correlation with the HU-DBI score. The majority of tobacco consumers were worried about the staining of teeth and bleeding from gums. A dental visit for a routine preventive check-up was reported to be rare in both groups.

Conclusion: The oral hygiene and gingival status were significantly poor in tobacco consumers compared to non-tobacco consumers. As the oral health behavior of the participants improved, the plaque and gingival scores reduced significantly.
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http://dx.doi.org/10.1155/2021/3548132DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8448612PMC
September 2021

Assessment of Anterior Loop of Inferior Alveolar Nerve and Its Anatomic Variations with Age, Gender, and Dentition Status in Indian Population: A CBCT Study.

Int J Dent 2021 31;2021:1813603. Epub 2021 Aug 31.

Department of Oral Medicine and Radiology, Saraswati Dental College, Lucknow 227105, India.

Background: The posterior region of the mandible is more often related to iatrogenic errors, but the interforaminal region is also not spared for neurovascular complications. This study aimed to use CBCT images to evaluate the prevalence of anterior nerve looping and its variations with age, gender, and dentition status.

Methods: This retrospective study was carried out by studying 600 CBCT scans retrieved from archival records of a CBCT center in Lucknow. The scans were inspected by two trained investigators. The length of the anterior loop was measured using the measuring tool of Carestream 3D imaging software. Descriptive and analytical tests were performed.

Results: The prevalence of the anterior loop of the inferior alveolar nerve was found to be 56%. The prevalence was found to be more on the right side (29.0%) compared to the left side (27.0%). The most common anterior looping of the inferior alveolar nerve was type 3 followed by type 1. Males were found to have significantly higher loops compared to females. The number of loops was found to decrease significantly with age. The mean length of the loop was found to vary from 1.14 to 1.61 mm.

Conclusion: The anterior looping of IAN is very much prevalent in the Lucknow population. The use of the CBCT technique and appropriate preplanning prior to surgery or implant placement should be performed to prevent nerve injury.
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http://dx.doi.org/10.1155/2021/1813603DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8424254PMC
August 2021

MAP4K4 promotes pancreatic tumorigenesis via phosphorylation and activation of mixed lineage kinase 3.

Oncogene 2021 Sep 13. Epub 2021 Sep 13.

Department of Surgery, Division of Surgical Oncology, the University of Illinois at Chicago, Chicago, IL, 60612, USA.

MAP4K4 is a Ste20 member and reported to play important roles in various pathologies, including in cancer. However, the mechanism by which MAP4K4 promotes pancreatic cancer is not fully understood. It is suggested that MAP4K4 might function as a cancer promoter via specific downstream target(s) in an organ-specific manner. Here we identified MLK3 as a direct downstream target of MAP4K4. The MAP4K4 and MLK3 associates with each other, and MAP4K4 phosphorylates MLK3 on Thr738 and increases MLK3 kinase activity and downstream signaling. The phosphorylation of MLK3 by MAP4K4 promotes pancreatic cancer cell proliferation, migration, and colony formation. Moreover, MAP4K4 is overexpressed in human pancreatic tumors and directly correlates with the disease progression. The MAP4K4-specific pharmacological inhibitor, GNE-495, impedes pancreatic cancer cell growth, migration, induces cell death, and arrests cell cycle progression. Additionally, the GNE-495 reduced the tumor burden and extended survival of the KPC mice with pancreatic cancer. The MAP4K4 inhibitor also reduced MAP4K4 protein expression, tumor stroma, and induced cell death in murine pancreatic tumors. These findings collectively suggest that MLK3 phosphorylation by MAP4K4 promotes pancreatic cancer, and therefore therapies targeting MAP4K4 might alleviate the pancreatic cancer tumor burden in patients.
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http://dx.doi.org/10.1038/s41388-021-02007-wDOI Listing
September 2021

Appraisal of contamination of heavy metals and health risk in agricultural soil of Jhansi city, India.

Environ Toxicol Pharmacol 2021 Sep 13;88:103740. Epub 2021 Sep 13.

Division of Environment Science, ICAR-Indian Agricultural Research Institute, New Delhi, 110012, India.

The accumulation of heavy metals (HMs) in soil is presently a significant threat to the environment. The Cu, Mn, Zn, Cd, Pb, Ni, and Co concentrations were assessed in the agricultural soil samples. The results of various contamination indices including contamination factor, geo-accumulation indices, and ecological risk indices revealed that Cd is responsible for moderate to high contamination of soil. The multivariate statistical analyses including PCA, HCA, and correlation matrix suggested the mixed origin of HMs in the soil. Ingestion was found to be a primary route of exposure while dermal and inhalation exposure was negligible. Overall, the non-carcinogenic health risks were well within the safe limit to human health. However, healthwise, children were likely to be at greater risk compared with adults, due to their generally increased exposure to toxic agents through hand/mouth ingestion. Moreover, no carcinogenic risks were determined through the inhalation exposure of Cd, Ni, and Co.
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http://dx.doi.org/10.1016/j.etap.2021.103740DOI Listing
September 2021

Intrinsic physicochemical profile of marketed antibody-based biotherapeutics.

Proc Natl Acad Sci U S A 2021 Sep;118(37)

Biotherapeutics Discovery, Boehringer Ingelheim, Ridgefield, CT 06877

Feeding biopharma pipelines with biotherapeutic candidates that possess desirable developability profiles can help improve the productivity of biologic drug discovery and development. Here, we have derived an in silico profile by analyzing computed physicochemical descriptors for the variable regions (Fv) found in 77 marketed antibody-based biotherapeutics. Fv regions of these biotherapeutics demonstrate significant diversities in their germlines, complementarity determining region loop lengths, hydrophobicity, and charge distributions. Furthermore, an analysis of 24 physicochemical descriptors, calculated using homology-based molecular models, has yielded five nonredundant descriptors whose distributions represent stability, isoelectric point, and molecular surface characteristics of their Fv regions. Fv regions of candidates from our internal discovery campaigns, human next-generation sequencing repertoires, and those in clinical-stages (CST) were assessed for similarity with the physicochemical profile derived here. The Fv regions in 33% of CST antibodies show physicochemical properties that are dissimilar to currently marketed biotherapeutics. In comparison, physicochemical characteristics of ∼29% of the Fv regions in human antibodies and ∼27% of our internal hits deviated significantly from those of marketed biotherapeutics. The early availability of this information can help guide hit selection, lead identification, and optimization of biotherapeutic candidates. Insights from this work can also help support portfolio risk assessment, in-licensing, and biopharma collaborations.
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http://dx.doi.org/10.1073/pnas.2020577118DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8449350PMC
September 2021

Sensing Molecules with Metal-Organic Framework Functionalized Graphene Transistors.

Adv Mater 2021 Oct 8;33(43):e2103316. Epub 2021 Sep 8.

Institute of Nanotechnology, Karlsruhe Institute of Technology, 76021, Karlsruhe, Germany.

Graphene is inherently sensitive to vicinal dielectrics and local charge distributions, a property that can be probed by the position of the Dirac point in graphene field-effect transistors. Exploiting this as a useful sensing principle requires selectivity; however, graphene itself exhibits no molecule-specific interaction. Complementarily, metal-organic frameworks can be tailored to selective adsorption of specific molecular species. Here, a selective ethanol sensor is demonstrated by growing a surface-mounted metal-organic framework (SURMOF) directly onto graphene field-effect transistors (GFETs). Unprecedented shifts of the Dirac point, as large as 15 V, are observed when the SURMOF/GFET is exposed to ethanol, while a vanishingly small response is observed for isopropanol, methanol, and other constituents of the air, including water. The synthesis and conditioning of the hybrid materials sensor with its functional characteristics are described and a model is proposed to explain the origin, magnitude, and direction of the Dirac point voltage shift. Tailoring multiple SURMOFs to adsorb specific gases on an array of such devices thus generates a versatile, selective, and highly sensitive platform for sensing applications.
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http://dx.doi.org/10.1002/adma.202103316DOI Listing
October 2021

Nonimmunogenic Hydrogel-Mediated Delivery of Antibiotics Outperforms Clinically Used Formulations in Mitigating Wound Infections.

ACS Appl Mater Interfaces 2021 Sep 7;13(37):44041-44053. Epub 2021 Sep 7.

Laboratory of Nanotechnology and Chemical Biology, Regional Centre for Biotechnology, NCR Biotech Science Cluster, 3rd Milestone, Faridabad-Gurgaon Expressway, Faridabad 121001, Haryana, India.

Treatment of chronic wound infections caused by Gram-positive bacteria such as is highly challenging due to the low efficacy of existing formulations, thereby leading to drug resistance. Herein, we present the synthesis of a nonimmunogenic cholic acid-glycine-glycine conjugate () that self-assembles into a supramolecular viscoelastic hydrogel ( gel) suitable for topical applications. The hydrogel can entrap different antibiotics with high efficacy without compromising its viscoelastic behavior. Activities against different bacterial species using a disc diffusion assay demonstrated the antimicrobial effect of the ciprofloxacin-loaded hydrogel (CPF-Gel). Immune profiling and gene expression studies after the application of the gel to mice confirmed its nonimmunogenic nature to host tissues. We further demonstrated that topical application of CPF-Gel clears -mediated wound infections more effectively than clinically used formulations. Therefore, cholic acid-derived hydrogels are an efficacious matrix for topical delivery of antibiotics and should be explored further.
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http://dx.doi.org/10.1021/acsami.1c12265DOI Listing
September 2021

Ambipolar Charge Transport Properties of Naphthophenanthridine Discotic Liquid Crystals.

J Phys Chem B 2021 Sep 6;125(36):10364-10372. Epub 2021 Sep 6.

Soft Condensed Matter Group, Raman Research Institute, C.V.Raman Avenue, Bengaluru 560080, India.

A series of novel naphthophenanthridine derivatives are synthesized via N-annulation of hexabutoxytriphenylene-1-amine with various aliphatic aldehydes through the Pictet-Spengler reaction. The synthesized derivatives have been found to self-assemble into a columnar hexagonal mesophase over a wide temperature range, as validated through polarized optical microscopy, differential scanning calorimetry and X-ray diffraction experiments. The photophysical properties of these compounds were studied using UV-visible and emission spectroscopy. The synthesized compounds exhibit ambipolar charge transport, showing temperature-independent electron and hole mobility on the order of 3 × 10 cm/V s, as evaluated by the time-of-flight technique. These novel N-annulated derivatives can be of immense potential toward semiconducting applications of self-assembling supramolecular systems.
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http://dx.doi.org/10.1021/acs.jpcb.1c06009DOI Listing
September 2021

A hydrogel-based implantable multidrug antitubercular formulation outperforms oral delivery.

Nanoscale 2021 Aug 30;13(31):13225-13230. Epub 2021 Jul 30.

Laboratory of Nanotechnology and Chemical Biology, Regional Centre for Biotechnology, NCR Biotech Science Cluster, 3rd Milestone, Faridabad-Gurgaon Expressway, Faridabad-121001, Haryana, India.

We present a non-immunogenic, injectable, low molecular weight, amphiphilic hydrogel-based drug delivery system (TB-Gel) that can entrap a cocktail of four front-line antitubercular drugs, isoniazid, rifampicin, pyrazinamide, and ethambutol. We showed that TB-Gel is more effective than oral delivery of the combination of four drugs in reducing the mycobacterial infection in mice. Results show that half the dose of chemotherapeutic drugs is sufficient to achieve a comparable therapeutic effect to that of oral delivery.
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http://dx.doi.org/10.1039/d0nr08806dDOI Listing
August 2021

Role of Zoledronic Acid Supplementation in Reducing Post-Surgical Recurrence of Giant Cell Tumor of Bone: A Meta-Analysis of Comparative Studies.

Cureus 2021 Jul 29;13(7):e16742. Epub 2021 Jul 29.

Orthopaedics, Hamdard Institute of Medical Sciences and Research, New Delhi, IND.

Zoledronic acid is a bisphosphonate that has recently gained interest in adjuvant therapy for giant cell tumor of bone (GCTB). It has an apoptotic effect on osteoclasts that are precursors of GCTB. However, the evidence suggesting the role of zoledronic acid in preventing GCTB recurrence is mixed, and therefore, a consensus is yet to be established. The purpose of the current meta-analysis was to analyze the impact of zoledronic acid supplementation on tumor recurrence in surgical treated GCTB. A systematic search was conducted on PubMed, Embase, and Web of Science databases to identify studies that analyzed the impact of local or systemic zoledronic acid supplementation on clinical outcomes in surgically treated GCTB. The data from the comparative studies were pooled and analyzed to investigate the association of zoledronic acid supplementation with tumor recurrence. Additionally, other factors such as age, gender, soft tissue extension, polymethyl methacrylate (PMMA) cement application, recurrent presentation, and extended curettage were also investigated for any association with tumor recurrence. Of the 271 results, 13 unique studies reported the clinical outcomes in GCTB. Seven studies compared the outcomes of zoledronic acid supplementation with control groups. Six studies presented the tumor recurrence-related data among the comparison groups. The zoledronic acid supplementation was associated with significantly lower tumor recurrence rates (p = 0.007). Additionally, a significant association of soft tissue extension and non-usage of PMMA cement with tumor recurrence were observed. The current meta-analysis suggests that zoledronic acid supplementation reduces tumor recurrence rates in surgically treated GCTB. We, therefore, recommend the use of zoledronic acid following aggressive extended curettage of the tumor. Further, well-planned randomized controlled trials will help strengthen this evidence.
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http://dx.doi.org/10.7759/cureus.16742DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8403108PMC
July 2021

Effect of charged mutation on aggregation of a pentapeptide: Insights from molecular dynamics simulations.

Proteins 2021 Aug 30. Epub 2021 Aug 30.

Protein Bioinformatics Laboratory, Department of Biotechnology, Indian Institute of Technology Madras, Chennai, India.

Aggregation of therapeutic monoclonal antibodies (mAbs) can negatively affect their chemistry, manufacturing, and control attributes and lead to undesirable immune responses in patients. Therefore, optimization of lead mAb drug candidates during discovery stages to mitigate aggregation is increasingly becoming an integral part of their developability assessments. The disruption of short sequence motifs called aggregation prone regions (APRs) found in amino acid sequences of mAb candidates can potentially mitigate their aggregation. In this work, we have performed molecular dynamics simulations to study the aggregation of an APR (VLVIY) found in λ light chains of human antibodies and its single point mutant KLVIY. Eighteen different multicopy peptide simulation systems of "VLVIY" and "KLVIY" were constructed by varying their concentrations, temperatures, termini capping, and flanking gate-keeper regions. Within 20 ns of the simulation, peptide "VLVIY" formed an aggregate of 100 peptides at ~0.1 M concentration with a 60% reduction in solvent accessible surface area (SASA). Furthermore, analysis of the SASA change, peptide cluster distribution, and water residence time demonstrated how Val ➔ Lys mutation resists aggregation and improves solubility. Presence of Lys slows down aggregation kinetics via charge-charge repulsions and by raising the kinetic barrier to formation of large oligomers. However, the effect of the Val ➔ Lys mutation is dependent on sequence and structural contexts around the APR. This mutation also alters the solvation shell around the peptide by favoring solute-solvent interactions, thereby increasing its solubility. This work has provided a detailed mechanistic explanation of how APR disruption can mitigate aggregation in biotherapeutics and improve their developability.
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http://dx.doi.org/10.1002/prot.26230DOI Listing
August 2021

Free Amine, Hydroxyl and Sulfhydryl Directed C-H Functionalization and Annulation: Application to Heterocycle Synthesis.

Chem Rec 2021 Aug 26. Epub 2021 Aug 26.

Chemical Technology Division, CSIR- Institute of Himalayan Bioresource Technology, Palampur, 176061, H.P.

Transition metal-catalyzed direct C-H bond functionalization is recognized as an efficient strategy to assemble heterocyclic frameworks. For this purpose, directing groups (DGs) installation on an organic molecule has remained a widely exploited strategy for the years. The installation of directing groups, especially for the amine, alcohol and thiol containing reactants and their removal after the reaction need additional steps. In this regard, the use of free amine, hydroxyl and sulfhydryl as directing groups in native form is advantageous and in recent times, these transformations have stirred undisputable advancements for applications to heterocycle synthesis. In this review, the aromatic sp -C attached free amine, hydroxyl and sulfhydryl as native functionalities are shown to be useful for the construction of five to seven-membered N-, O- and S-heterocycles.
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http://dx.doi.org/10.1002/tcr.202100171DOI Listing
August 2021
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