Publications by authors named "Sudhir Kumar"

491 Publications

MRI-Based Morphometric Study Regarding Operative Windows of Oblique Lumbar Interbody Fusion in Indian Population.

Indian J Orthop 2021 Jul 7;55(Suppl 2):366-373. Epub 2021 Apr 7.

Department of Orthopaedics, School of Medical Sciences and Research, Sharda University, Greater Noida, Uttar Pradesh India.

Background: The novel Oblique lumbar interbody fusion [OLIF] technique has been proposed as a solution to approach related complications of anterior lumbar interbody fusion [ALIF] and lateral lumbar interbody fusion [LLIF]. There exists no study concerning morphological evaluation of retroperitoneal oblique corridor for the Oblique lumbar interbody fusion (OLIF) technique in the Indian population. The aim of our study was (a) to measure magnetic resonance imaging (MRI) based anatomic parameters concerning OLIF operative windows from L2-L3 to L4-L5 level (b) to determine the feasibility of this technique following MRI-based morphometric evaluation in the Indian population.

Material And Methods: We did retrospective MRI analysis of 307 consecutive patients following our exclusion criteria. Bare window, psoas major window and psoas major width were measured from axial T2 MRI image taken at mid disc level from L2-L3 to L4-L5 levels.

Results: The mean bare window size was largest at L2-L3 (1.39 cm) level followed by L3-L4 and L4-L5 level (1.28 and 0.62 cm respectively), and differences between them were statistically significant ( < 0.001). Females had statistically significant larger bare windows at L2-L3 and L3-L4 level than males ( < 0.001). With increasing age, there was a significant increase in bare window size at each level ( < 0.001). The mean psoas major window (PM and mean psoas major width (PM were largest at L4-L5 level (PM = 1.27 cm, PM = 3.61 cm) followed by L3-L4 and L2-L3 level (L3-L4: PM = 1.19 cm, PM = 2.36 cm; L2-L3: PM = 0.88 cm, PM = 1.39 cm), and differences among each level concerning both parameters were statistically significant ( < 0.001). Both parameters (PM, PM) were significantly larger in males than females at each level ( < 0.001).

Conclusion: The OLIF technique is well suited for lumbar interbody fusion at L2 -L3 and L3-L4 level in the Indian population irrespective of age and sex. At L4-L5 level, overall 17.9 percent of the study population were unsuitable for this technique due to inaccessible bare window. In our opinion, this level may be better suited for OLIF approach in the elderly Indian population, especially for surgeons who are beginning to attempt this technique in their surgical practice. Preoperative MRI evaluation for the OLIF is important to assess its feasibility, as there exists significant age and gender differences in the Indian population for anatomic parameters concerning OLIF operative windows from L2-L3 to L4-L5 levels.

Supplementary Information: The online version contains supplementary material available at 10.1007/s43465-021-00393-7.
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http://dx.doi.org/10.1007/s43465-021-00393-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8275717PMC
July 2021

Data-driven speciation tree prior for better species divergence times in calibration-poor molecular phylogenies.

Bioinformatics 2021 07;37(Suppl_1):i102-i110

Institute for Genomics and Evolutionary Medicine, Temple University, Philadelphia, PA 19122, USA.

Motivation: Precise time calibrations needed to estimate ages of species divergence are not always available due to fossil records' incompleteness. Consequently, clock calibrations available for Bayesian dating analyses can be few and diffused, i.e. phylogenies are calibration-poor, impeding reliable inference of the timetree of life. We examined the role of speciation birth-death (BD) tree prior on Bayesian node age estimates in calibration-poor phylogenies and tested the usefulness of an informative, data-driven tree prior to enhancing the accuracy and precision of estimated times.

Results: We present a simple method to estimate parameters of the BD tree prior from the molecular phylogeny for use in Bayesian dating analyses. The use of a data-driven birth-death (ddBD) tree prior leads to improvement in Bayesian node age estimates for calibration-poor phylogenies. We show that the ddBD tree prior, along with only a few well-constrained calibrations, can produce excellent node ages and credibility intervals, whereas the use of an uninformative, uniform (flat) tree prior may require more calibrations. Relaxed clock dating with ddBD tree prior also produced better results than a flat tree prior when using diffused node calibrations. We also suggest using ddBD tree priors to improve the detection of outliers and influential calibrations in cross-validation analyses.These results have practical applications because the ddBD tree prior reduces the number of well-constrained calibrations necessary to obtain reliable node age estimates. This would help address key impediments in building the grand timetree of life, revealing the process of speciation and elucidating the dynamics of biological diversification.

Availability And Implementation: An R module for computing the ddBD tree prior, simulated datasets and empirical datasets are available at https://github.com/cathyqqtao/ddBD-tree-prior.
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http://dx.doi.org/10.1093/bioinformatics/btab307DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8275332PMC
July 2021

Bioleaching of metals from waste printed circuit boards using bacterial isolates native to abandoned gold mine.

Biometals 2021 Jul 2. Epub 2021 Jul 2.

Department of Biotechnology and Bioinformatics, Jaypee University of Information Technology, Himachal Pradesh, Waknaghat, Solan, 173234, India.

In the present study, native bacterial strains isolated from abandoned gold mine and Chromobacterium violaceum (MTCC-2656) were applied for bioleaching of metals from waste printed circuit boards (WPCBs). Toxicity assessment and dose-response analysis of WPCBs showed EC values of 128.9, 98.7, and 90.8 g/L for Bacillus sp. SAG3, Bacillus megaterium SAG1 and Lysinibacillus sphaericus SAG2, respectively, whereas, for C. violaceum EC was 83.70 g/L. This indicates the viable operation range and technological feasibility of metals bioleaching from WPCBs using mine isolates. The influencing factors such as pH, pulp density, temperature, and precursor molecule (glycine) were optimized by one-factor at a time method (OFAT). The maximum metal recovery occurred at an initial pH of 9.0, a pulp density of 10 g/L, a temperature of 30 °C and a glycine concentration of 5 g/L, except for L. sphaericus which showed optimum activity at initial pH of 8.0. Under optimal conditions the metals recovery of Cu and Au from WPCBs were recorded as 87.5 ± 8% and 73.6 ± 3% for C. violaceum and 72.7 ± 5% and 66.6 ± 6% for B. megaterium, respectively. Kinetic modeling results showed that the data was best described by first order reaction kinetics, where the rate of metal solubilization from WPCBs depended upon microbial lixiviant production. This is the first report on bioleaching of metals from e-waste using bacterial isolates from the gold mine of Solan, HP. Our study demonstrated the potential of bioleaching for resource recovery from WPCBs dust, aimed to be disposed at landfills, and its effectiveness in extraction of elements those are at high supply risk and demand.
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http://dx.doi.org/10.1007/s10534-021-00326-9DOI Listing
July 2021

Pronator Quadratus Hemangioma (PQH): A Rare Case Report and Review.

Indian J Orthop 2021 Aug 8;55(4):1056-1063. Epub 2021 Jan 8.

Department of Orthopaedics, School of Medical Sciences and Research, Sharda University, Greater Noida, Uttar Pradesh 201 306 India.

The intramuscular hemangioma is a rare clinical entity in the upper extremity. Pronator quadratus hemangioma poses a considerable morbidity in the functional quality of life of an individual. MRI remains the gold standard modality in diagnosing this rare entity. Additionally, histopathological examination of the lesion corroborates for the same. PQH follows an individualized protocol in the management of the tumour. A 35-year-old female presented with pain over her right wrist from past 1 year which was dull aching, non-radiating, localised to the palmar aspect of distal 1/3rd of the right forearm. There was no history of trauma or infection over the right wrist. Swelling was present over the palmar aspect of distal 1/3rd of right forearm, which was non-pulsatile, non-fluctuant, non-transilluminant, non-compressible, non-reducible and skin over the swelling was pinchable. The movements of the right wrist were painful and restricted. There was no distal neurovascular deficit. The MRI of her right wrist and hand suggested the presence of low flow vascular malformation within pronator quadratus muscle. The patient underwent excision biopsy of pronator quadratus in toto without any neurological complications. No recurrence was noted in the follow-up period for 12 months. The pronator quadratus hemangioma is a rare clinical entity where the natural course of disease and pathophysiology remains controversial. MRI serves as the gold standard in the diagnosis of intramuscular hemangioma. The management of such tumour has to be individualized based on the functional needs of the patient. The natural course of the disease has to be elicited to decrease the morbidity and enhance the functional quality of life of the patient.
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http://dx.doi.org/10.1007/s43465-020-00295-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8192677PMC
August 2021

Tibial Nerve Schwannoma: An Unexplained Cause of Lateral Foot Pain - A Rare Case Report and Review.

J Orthop Case Rep 2020 Dec;10(9):1-6

Department of Orthopaedics, School of Medical Sciences and Research, Sharda University, Greater Noida, Uttar Pradesh. India.

Introduction: Schwannoma is a benign tumor that arises from the peripheral nerve sheath. It presents as a discrete, often tender, and palpable nodule associated with neurogenic pain or paresthesia when compressed or traumatized. The growth rate is usually slow, and these lesions seldom exceed 2 cm in diameter.

Case Report: We report the case of a schwannoma arising from the tibial nerve located in the left popliteal fossa. The patient presented with the left foot pain in the lateral plantar region without any motor deficit. The pre-operative diagnosis was made with magnetic resonance imaging (MRI) scan. He was subjected for neurolysis and excision biopsy of the lesion. The surgical specimen consisted of encapsulated white-yellow mass with irregular contours, measuring 2 × 3 cm. The cut section revealed cystic degenerations with areas of hemorrhage and necrosis. The patient reported symptom free in the post-operative period and during follow-up. Marginal excision appears to be recommended therapy for this tumorous lesion, without any evidence of recurrence during follow-up.

Conclusion: A benign nerve sheath tumor of a peripheral nerve could be a possibility for long-standing neuropathic pain in the foot, ankle, and leg, wherein all other possibilities have been ruled out. The meticulous examination of the entire length of the tibial nerve including sciatic nerve by palpation and percussion was helpful in diagnosis which should be confirmed by MRI scan. The excision biopsy remains the gold standard treatment of choice for schwannoma of the peripheral nerve.
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http://dx.doi.org/10.13107/jocr.2020.v10.i09.1880DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8046459PMC
December 2020

Floodplains landforms, clay deposition and irrigation return flow govern arsenic occurrence, prevalence and mobilization: A geochemical and isotopic study of the mid-Gangetic floodplains.

Environ Res 2021 Jun 21;201:111516. Epub 2021 Jun 21.

Discipline of Earth Sciences, Indian Institute of Technology, Gandhinagar, India. Electronic address:

This article attempts to understand the evolution of groundwater chemistry in the mid Gangetic floodplain through the identification of hydrogeochemical processes including the impact of surface recharge and geological features. Isotopic investigations identified that irrigation return flow is partly responsible for arsenic (As) enrichment through preferential vertical recharge. Further, the floodplain geomorphological attributes and associated As hydrogeochemical behaviour traced through isotopes tracers highlighted that meandering and ox-bow like geomorphological features owing to clay deposition leads to the anoxic condition induced reductive microbial dissolution of As-bearing minerals causing the arsenic contamination in the investigated aquifer of the mid-Gangetic plain (MGP). To achieve the objectives, 146 water samples for water chemistry and 62 samples for the isotopic study were collected from Bhojpur district, Bihar (district bounded by the river Ganges in the north and Son in the east) located in MGP during the pre-monsoon season of 2018. The chemical results revealed high arsenic concentration (BDL to 206 μg.L, 32% samples are exceeding the 10 μg.L limit) in the Holocene recent alluviums which are characterized by various geomorphological features such as meander scars and oxbow lake (northern part of the district). Arsenic is more concentrated in the depth range of 15-40 m below ground surface. All other trace metals viz. Ni, Pb, Zn, Cd and Al were found in low concentration except Fe and Mn. The geochemical analyses suggest that rock-water interaction is controlling the hydro-geochemistry while the chemical constituent of the groundwater is mainly controlled by carbonate weathering with limited contribution from silicate weathering. The isotopic signatures revealed that the Son river is recharging groundwater while the groundwater is contributing to the Ganges river. A clear pattern of fast vertical recharge in the arsenic contaminated area is observed in the proximity to the river Ganges with an elevated nitrate concentration resulted from the reduced As dissolution. The origin of groundwater is local precipitation with low to high evaporation enrichment effect which is further indicating the vertical mixing of groundwater from the irrigation return flow and/or recharge from domestic discharge causing enhanced As mobilization through microbial assisted reductive dissolution of As-bearing minerals.
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http://dx.doi.org/10.1016/j.envres.2021.111516DOI Listing
June 2021

Hoffa Fracture in Skeletally Immature Patients: A Case Report and Review of Literature.

J Orthop Case Rep 2021 Feb;11(2):112-118

Department of Orthopaedics, School of Medical Sciences and Research, Sharda University, Greater Noida, Uttar Pradesh, India.

Introduction: Hoffa fractures are the fractures of the femoral condyles in the coronal planes. These are uncommon in adults and notably rarer in pediatric population. In this fracture, either one or both the femoral condyles may get involved following the injury. Such rare clinical entity warrants a high index of suspicion with apt radiological corroboration for meticulously diagnosing and planning out the treatment.

Case Report: We report a rare case of Hoffa fracture involving the medial femoral condyle of right knee and undisplaced right patella fracture in a 6-year-old girl. The radiological investigations (radiographs and computed tomography [CT] scan) were done and her leg was immobilized by above knee posterior slab. Our treatment plan included surgical intervention to do open reduction and internal fixation using k-wires and two 4.5 mm partially threaded cannulated cancellous screws and was done with due care to prevent any damage to epiphysis. No signs of osteonecrosis, heterotopic ossification or physeal growth arrest in radiograph taken at 10th month were noted. The child is still under follow-up.

Conclusion: Hoffa fracture is a rare variety and the diagnosis of the same warrant a higher index of suspicion with more watchful eye. CT-scan firmly establishes the missed diagnosis and notably provides with the detailed configuration of the fracture to guide the treatment plan. Surgical intervention (open reduction and fixation or arthroscopy based procedures) is essential over the non-operative treatment to alleviate complications.
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http://dx.doi.org/10.13107/jocr.2021.v11.i02.2050DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8180317PMC
February 2021

State of the Art and Prospects for Halide Perovskite Nanocrystals.

ACS Nano 2021 Jun 17. Epub 2021 Jun 17.

Department of Materials Science and Engineering, and Centre for Functional Photonics (CFP), City University of Hong Kong, 83 Tat Chee Avenue, Kowloon, Hong Kong S.A.R.

Metal-halide perovskites have rapidly emerged as one of the most promising materials of the 21st century, with many exciting properties and great potential for a broad range of applications, from photovoltaics to optoelectronics and photocatalysis. The ease with which metal-halide perovskites can be synthesized in the form of brightly luminescent colloidal nanocrystals, as well as their tunable and intriguing optical and electronic properties, has attracted researchers from different disciplines of science and technology. In the last few years, there has been a significant progress in the shape-controlled synthesis of perovskite nanocrystals and understanding of their properties and applications. In this comprehensive review, researchers having expertise in different fields (chemistry, physics, and device engineering) of metal-halide perovskite nanocrystals have joined together to provide a state of the art overview and future prospects of metal-halide perovskite nanocrystal research.
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http://dx.doi.org/10.1021/acsnano.0c08903DOI Listing
June 2021

The power and promise of genetic mapping from Plasmodium falciparum crosses utilizing human liver-chimeric mice.

Commun Biol 2021 06 14;4(1):734. Epub 2021 Jun 14.

Host Pathogen Interactions Program, Texas Biomedical Research Institute, San Antonio, TX, USA.

Genetic crosses are most powerful for linkage analysis when progeny numbers are high, parental alleles segregate evenly and numbers of inbred progeny are minimized. We previously developed a novel genetic crossing platform for the human malaria parasite Plasmodium falciparum, an obligately sexual, hermaphroditic protozoan, using mice carrying human hepatocytes (the human liver-chimeric FRG NOD huHep mouse) as the vertebrate host. We report on two genetic crosses-(1) an allopatric cross between a laboratory-adapted parasite (NF54) of African origin and a recently patient-derived Asian parasite, and (2) a sympatric cross between two recently patient-derived Asian parasites. We generated 144 unique recombinant clones from the two crosses, doubling the number of unique recombinant progeny generated in the previous 30 years. The allopatric African/Asian cross has minimal levels of inbreeding and extreme segregation distortion, while in the sympatric Asian cross, inbred progeny predominate and parental alleles segregate evenly. Using simulations, we demonstrate that these progeny provide the power to map small-effect mutations and epistatic interactions. The segregation distortion in the allopatric cross slightly erodes power to detect linkage in several genome regions. We greatly increase the power and the precision to map biomedically important traits with these new large progeny panels.
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http://dx.doi.org/10.1038/s42003-021-02210-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8203791PMC
June 2021

Fibrolipomatous Hamartoma (FLH) of Median Nerve: A Rare Case Report and Review.

Indian J Orthop 2021 May 1;55(Suppl 1):267-272. Epub 2020 Jun 1.

Department of Orthopaedics, School of Medical Sciences and Research, Sharda University, Greater Noida, Uttar Pradesh 201 306 India.

Introduction: Fibrolipomatous hamartoma (FLH) is a benign tumorous condition of adipose tissue. It is a slow growing, rare tumour involving peripheral nerves with uncertain aetiology. The clinical presentation varies as per presenting severity. The gold standard to diagnose this rare entity is MRI and its management is still controversial. In this report, we have described one such rare presentation of FLH involving Median Nerve in an adolescent male who successfully witnessed resolution of symptoms following our surgical intervention for the same.

Case Presentation: A 17-year-old male presented to our hospital with a history of swelling in his left hand since past 1 year. The detailed clinical evaluation revealed an irregular fusiform swelling extending from the ulnar aspect of wrist proximally to the thenar eminence along with involvement of the base of 2nd, 3rd and 4th fingers of left hand with consistency varying from soft to firm, tinel's sign positive and a terminal restriction of palmar and dorsiflexion movements. Notably, motor weakness and sensory loss were not elicited. The definitive diagnosis was established by MRI of the left hand. With due consent, the patient was undertaken for surgical intervention whereby his carpal tunnel was decompressed and biopsy of the lesion was sent for further histopathological evaluation as per the protocol. The absolute resolution in symptoms was reported by the patient following our intervention.

Conclusion: A meticulous clinical and radiological correlation is required to diagnose such rare clinical entity for improvising the functional quality of life. There is no definitive treatment for lipomatosis of nerve. However, a conservative approach is commonly advocated with successful results from decompression as in our patient.
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http://dx.doi.org/10.1007/s43465-020-00149-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8149561PMC
May 2021

Platelet derived growth factor receptor β (PDGFRβ) is a host receptor for the human malaria parasite adhesin TRAP.

Sci Rep 2021 May 31;11(1):11328. Epub 2021 May 31.

Seattle Children's Research Institute, Seattle, WA, USA.

Following their inoculation by the bite of an infected Anopheles mosquito, the malaria parasite sporozoite forms travel from the bite site in the skin into the bloodstream, which transports them to the liver. The thrombospondin-related anonymous protein (TRAP) is a type 1 transmembrane protein that is released from secretory organelles and relocalized on the sporozoite plasma membrane. TRAP is required for sporozoite motility and host infection, and its extracellular portion contains adhesive domains that are predicted to engage host receptors. Here, we identified the human platelet-derived growth factor receptor β (hPDGFRβ) as one such protein receptor. Deletion constructs showed that the von Willebrand factor type A and thrombospondin repeat domains of TRAP are both required for optimal binding to hPDGFRβ-expressing cells. We also demonstrate that this interaction is conserved in the human-infective parasite Plasmodium vivax, but not the rodent-infective parasite Plasmodium yoelii. We observed expression of hPDGFRβ mainly in cells associated with the vasculature suggesting that TRAP:hPDGFRβ interaction may play a role in the recognition of blood vessels by invading sporozoites.
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http://dx.doi.org/10.1038/s41598-021-90722-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8166973PMC
May 2021

How to Build a Super Predator: From Genotype to Phenotype.

Am Biol Teach 2021 Mar;83(3):138-146

Temple University, Philadelphia, PA 19122.

We present a drawing discovery lab that crosscuts multiple disciplines in biology and links concepts in genetics and evolutionary thinking to enhance understanding of the genotype-to-phenotype transformation. These combined concepts are also linked to ecological frameworks in nature through the model of biological plasticity. Students and teachers explore drawing skills to flesh out the future of a predator while engaging with the computational software MEGA, which introduces students and teachers to nucleotide changes, mutations, variation, phylogenetics, and molecular evolution.
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http://dx.doi.org/10.1525/abt.2021.83.3.138DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8130183PMC
March 2021

Scanning electron microscopy of Cysticercus fasciolaris (larval Taenia taeniaeformis Batsch, 1786) from the wild rat, Rattus rattus Linnaeus, 1758, morpho-physiology and risk to human health.

Ann Parasitol 2021 ;67(1):31-38

Department of Life Science, Chhatrapati Shahu Ji Maharaj University, Kanpur 208024, UP, India.

Autopsy of Rattus rattus (n=65) revealed 1-7 creamish to white cysts, 2-7 mm in diameter embedded in the liver parenchyma of 12 rats. Dissection yielded 45-65 mm×5 mm sized segmented strobilocercii of Cysticercus fasciolaris (larval Taenia taeniaeformis) coiled inside. Light microscopy indicated large scolices, the rostellum armed with four suckers and one row of taenoid type hooks having long blunt handle with sharp pointed blade, other row of hooks was in the developing stage. The strobila lacked genital organs and ended in a tail-bulb suggesting it was juvenile. SEM showed anterior crown of 19 hooks and poorly developed posterior crown. A collar (66.0-86.0 μm in width) armed with papillae (30.2-35.4 μm base and 12.5-14.5 μm tip) and pores (17.0-22.4 μm in diameter) surrounded the hooks. The body segments were 125-145 μm in diameter, at the tail bud, 380-410 μm in diameter. The segments were armed with pores, 11.5-14.5 μm in diameter. Netted (2.5-4.5 μm wide and of varying lengths) body segments provide flexibility to the worm during attachment. The tail bud was 2.4-2.7 mm in length and 1.5-1.71 mm in width. The SEM data presents a significant advancement over light microscopy and the morphological features generated herein can safely be utilized to correlate with the parasite's physiological functions. This is the first report of R. rattus as a natural intermediate host of T. taeniaeformis, and may pose serious risk to human health in urban areas of Bareilly, India and merits attention.
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http://dx.doi.org/10.17420/ap6701.309DOI Listing
May 2021

Ligand-assisted solid phase synthesis of mixed-halide perovskite nanocrystals for color-pure and efficient electroluminescence.

J Mater Chem C Mater 2021 Mar 25;9(17):5771-5778. Epub 2021 Mar 25.

Institute for Chemical and Bioengineering, Department of Chemistry and Applied Biosciences, ETH Zürich Vladimir Prelog Weg 1 CH-8093 Zürich Switzerland

Colloidal nanocrystals (NCs) of lead halide perovskites have generated considerable interest in the fabrication of optoelectronic devices, such as light emitting-diodes (LEDs), because of their tunable optical bandgap, narrow spectral width, and high defect tolerance. However, the inhomogeneous halide distribution within individual NCs remains a critical challenge in order to obtain color-stable electroluminescence in mixed-halide systems. Here, we demonstrate a new post-synthetic approach, ligand-assisted solid phase synthesis (LASPS), for the preparation of electroluminescent colloidal NCs of methylammonium (MA) lead halide perovskites, at room temperature. The slow reaction kinetics preserves the morphology, size, and shape in the resulting NCs whose emission covers the entire visible spectral region with photoluminescence (PL) quantum yields (QYs) of up to >90% and colloidal stability up to several months. The LEDs fabricated using the prepared mixed-halide NCs display narrowband electroluminescence (EL) ranging from 476 to 720 nm. The optimized red LEDs exhibit an external quantum efficiency, , of up to 2.65%, with the CIE 1931 color coordinates of (0.705, 0.290), nearly identical to those of the red primary in the recommendation (rec.) 2020 standard (0.708, 0.292).
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http://dx.doi.org/10.1039/d0tc04667aDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8101407PMC
March 2021

Molecular and morphological clocks for estimating evolutionary divergence times.

BMC Ecol Evol 2021 05 12;21(1):83. Epub 2021 May 12.

Institute for Genomics and Evolutionary Medicine, Temple University, Philadelphia, PA, 19122, USA.

Background: Matrices of morphological characters are frequently used for dating species divergence times in systematics. In some studies, morphological and molecular character data from living taxa are combined, whereas others use morphological characters from extinct taxa as well. We investigated whether morphological data produce time estimates that are concordant with molecular data. If true, it will justify the use of morphological characters alongside molecular data in divergence time inference.

Results: We systematically analyzed three empirical datasets from different species groups to test the concordance of species divergence dates inferred using molecular and discrete morphological data from extant taxa as test cases. We found a high correlation between their divergence time estimates, despite a poor linear relationship between branch lengths for morphological and molecular data mapped onto the same phylogeny. This was because node-to-tip distances showed a much higher correlation than branch lengths due to an averaging effect over multiple branches. We found that nodes with a large number of taxa often benefit from such averaging. However, considerable discordance between time estimates from molecules and morphology may still occur as  some intermediate nodes may show large time differences between these two types of data.

Conclusions: Our findings suggest that node- and tip-calibration approaches may be better suited for nodes with many taxa. Nevertheless, we highlight the importance of evaluating the concordance of intrinsic time structure in morphological and molecular data before any dating analysis using combined datasets.
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http://dx.doi.org/10.1186/s12862-021-01798-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8117668PMC
May 2021

Molecular Memories of a Cambrian Fossil.

Am Biol Teach 2020 Nov-Dec;82(9):586-595

Department of Biology and Director of the Institute for Genomics and Evolutionary Medicine, Temple, University, Philadelphia, PA 19122.

Evolutionary evidence is important scientific background for appreciating the theory of evolution. We describe a STEAM-based lesson plan that uses paleontological drawings and a modern evolutionary database to explore and understand fossil, morphological, and molecular evidence. Together, with a focus on arthropods and the Cambrian explosion, students experience a heuristic process common in scientific reasoning, guiding them toward practices that synthesize knowledge and invite questioning in the life sciences.
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http://dx.doi.org/10.1525/abt.2020.82.9.586DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8104914PMC
May 2021

and growth inhibitory, anti-ovarian & anti-lung carcinoma effects of 1,5 diarylpenta-1,4-dien-3-one as synthetically modified curcumin analogue.

J Biomol Struct Dyn 2021 May 6:1-18. Epub 2021 May 6.

Department of Zoology, Molecular Endocrinology Lab, University of Lucknow, Lucknow, India.

The synthesized 1,5 diarylpenta-1,4-dien-3-one derivatives (compounds 1-6) as synthetic curcumin analogues were tested for their potential anticancer activity against human ovarian and lung adenocarcinoma cells. The absorption, distribution, metabolism, excretion, and toxicity (ADMET/pharmacokinetic) parameters of all the compounds were predicted by admetSAR software. The pharmacokinetics, pharmacodynamics and bioactivity scores properties based on Lipinski rule and Ghose filter, calculated with the help of Molinspiration and ChemDraw. Molecular docking evaluation of all the compounds was also performed by using AutoDock Vina and iGEMDOCK against three most common human anticancer targets; epidermal growth factor receptor (EGFR), heat shock protein (Hsp 90-α), and vascular endothelial growth factor receptor-2 (VEGFR2). The obtained results were compared with the reference compound 7 and drugs 8-10 (7: GO-035; 8: Quinazolin; 9: Naquotinib and 10: Ribofuranuronamide). Finding indicates, all the compounds were potentially interacting with VEGFR2 through the average -9.1 binding energy (BE) with closer contact <5.0 Å deep in the active site of the ligand-receptor complex. All the compounds showed excellent oral bioavailability, bioactivity score, and none of the compounds are virtually found to be toxic. Compounds 1-6 were also successfully characterized by the physical properties as well as spectroscopic techniques (FT-IR and H-NMR). anti-proliferative activity was tested MTT method against human ovarian carcinoma (PA-1) and human lung adenocarcinoma (A549) cells and further screened for apoptotic parameters such as nuclear fragmentation and ROS generation. Compound 4 exhibits good dose-dependent anti-proliferative activity (IC 73 and 79.7 µM) against human ovarian carcinoma and human lung adenocarcinoma, respectively.Communicated by Ramaswamy H. Sarma.
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http://dx.doi.org/10.1080/07391102.2021.1914166DOI Listing
May 2021

An Evolutionary Portrait of the Progenitor SARS-CoV-2 and Its Dominant Offshoots in COVID-19 Pandemic.

Mol Biol Evol 2021 Jul;38(8):3046-3059

Institute for Genomics and Evolutionary Medicine, Temple University, Philadelphia, PA, USA.

Global sequencing of genomes of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has continued to reveal new genetic variants that are the key to unraveling its early evolutionary history and tracking its global spread over time. Here we present the heretofore cryptic mutational history and spatiotemporal dynamics of SARS-CoV-2 from an analysis of thousands of high-quality genomes. We report the likely most recent common ancestor of SARS-CoV-2, reconstructed through a novel application and advancement of computational methods initially developed to infer the mutational history of tumor cells in a patient. This progenitor genome differs from genomes of the first coronaviruses sampled in China by three variants, implying that none of the earliest patients represent the index case or gave rise to all the human infections. However, multiple coronavirus infections in China and the United States harbored the progenitor genetic fingerprint in January 2020 and later, suggesting that the progenitor was spreading worldwide months before and after the first reported cases of COVID-19 in China. Mutations of the progenitor and its offshoots have produced many dominant coronavirus strains that have spread episodically over time. Fingerprinting based on common mutations reveals that the same coronavirus lineage has dominated North America for most of the pandemic in 2020. There have been multiple replacements of predominant coronavirus strains in Europe and Asia as well as continued presence of multiple high-frequency strains in Asia and North America. We have developed a continually updating dashboard of global evolution and spatiotemporal trends of SARS-CoV-2 spread (http://sars2evo.datamonkey.org/).
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http://dx.doi.org/10.1093/molbev/msab118DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8135569PMC
July 2021

Cutaneous mucormycosis in a chronic lymphocytic leukemia patient on ibrutinib.

IDCases 2021 12;24:e01120. Epub 2021 Apr 12.

Division of Infectious Diseases, UnityPoint Health, Des Moines, IA, USA.

Background: Mucorales is a zygomycete fungi known to cause opportunistic infections in immunosuppressed hosts. Spores may be inhaled, causing rhinocerebral or pulmonary infections, or gastrointestinal infections if swallowed. Less often, cutaneous mucormycosis develops after inoculation via broken skin.

Presentation: A 72-year old male on ibrutinib and prednisone for chronic lymphocytic leukemia (CLL) presented with localized, right forearm cutaneous mucormycosis at the site of a dog-scratch sustained three weeks prior. The patient failed to respond to cephalexin as an outpatient, prompting biopsy showing ribbon-like pseudo septate hyphae and possible vascular invasion suggestive of Mucorales. Treatment course included liposomal amphotericin B 5 mg/kg IV every 24 h for ten days followed by a 90-day course of posaconazole 300 mg daily after general surgery consultation was sought.

Conclusion: We outline the second reported case of localized cutaneous mucormycosis arising in the setting of ibrutinib use. Because the combination of immunosuppressed states, ibrutinib and skin trauma may serve as a nidus for mucormycosis, practitioners should be vigilant of thorough skin evaluations in these patients and appropriate anti-fungal treatment. Although amphotericin B has been well studied as first line therapy, oral posaconazole has been shown as an efficacious second-line treatment.
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http://dx.doi.org/10.1016/j.idcr.2021.e01120DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8065302PMC
April 2021

MEGA11: Molecular Evolutionary Genetics Analysis Version 11.

Mol Biol Evol 2021 Jun;38(7):3022-3027

Institute for Genomics and Evolutionary Medicine, Temple University, Philadelphia, PA, USA.

The Molecular Evolutionary Genetics Analysis (MEGA) software has matured to contain a large collection of methods and tools of computational molecular evolution. Here, we describe new additions that make MEGA a more comprehensive tool for building timetrees of species, pathogens, and gene families using rapid relaxed-clock methods. Methods for estimating divergence times and confidence intervals are implemented to use probability densities for calibration constraints for node-dating and sequence sampling dates for tip-dating analyses. They are supported by new options for tagging sequences with spatiotemporal sampling information, an expanded interactive Node Calibrations Editor, and an extended Tree Explorer to display timetrees. Also added is a Bayesian method for estimating neutral evolutionary probabilities of alleles in a species using multispecies sequence alignments and a machine learning method to test for the autocorrelation of evolutionary rates in phylogenies. The computer memory requirements for the maximum likelihood analysis are reduced significantly through reprogramming, and the graphical user interface has been made more responsive and interactive for very big data sets. These enhancements will improve the user experience, quality of results, and the pace of biological discovery. Natively compiled graphical user interface and command-line versions of MEGA11 are available for Microsoft Windows, Linux, and macOS from www.megasoftware.net.
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http://dx.doi.org/10.1093/molbev/msab120DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8233496PMC
June 2021

Impact of geology and anthropogenic activities over the water quality with emphasis on fluoride in water scarce Lalitpur district of Bundelkhand region, India.

Chemosphere 2021 Sep 5;279:130496. Epub 2021 Apr 5.

Groundwater Department WAPCOS, New Delhi, India.

The Bundelkhand region of India is suffering from acute water scarcity, raising concern over the potability in the region. Therefore, to develop a baseline data set of groundwater quality, sampling was carried out from the 110 existing shallow hand pumps and tube wells covering the Lalitpur district. Groundwater samples were investigated for hydro-geochemical and isotopic signatures (δO and δH) to understand the driving factors leading to water quality and its contamination in the region. The results of Hierarchical cluster analysis revealed four different clusters according to their water quality. Cluster 1 and 2 water samples have a good quality of water and these samples fall in the vicinity of major or minor drainage networks of the area. Whereas, clusters 3 and 4 are of deteriorated water quality and located far-off from the drainage networks in the study area. The findings from chemical analysis and chemometric method suggest that the groundwater composition is mainly influenced by rock weathering and anthropogenic activities. Fluoride exposure dosage for the infant and children is twice that of adults in the study area, indicating a stronger impact of fluoride concentration in infants and children. The stable isotopic analysis shows that origin of groundwater is local precipitation, with evaporative enrichment in groundwater. The groundwater of cluster 3 and 4 shows evaporative nature along with high EC and Cl concentration. The variation of concentration of ions in the study area prevails along the groundwater flow direction and surface drainage reveals the control of hydrogeological attributes in the groundwater.
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http://dx.doi.org/10.1016/j.chemosphere.2021.130496DOI Listing
September 2021

Epistasis produces an excess of invariant sites in neutral molecular evolution.

Proc Natl Acad Sci U S A 2021 May;118(18)

Institute for Genomics and Evolutionary Medicine, Temple University, Philadelphia, PA 19122;

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http://dx.doi.org/10.1073/pnas.2018767118DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8106334PMC
May 2021

Continuous color tuning of single-fluorophore emission via polymerization-mediated through-space charge transfer.

Sci Adv 2021 Apr 7;7(15). Epub 2021 Apr 7.

Institute of Pharmaceutical Sciences, Department of Chemistry and Applied Biosciences, ETH Zurich, Vladimir-Prelog-Weg 1-5/10, 8093 Zurich, Switzerland.

Tuning emission color of molecular fluorophores is of fundamental interest as it directly reflects the manipulation of excited states at the quantum mechanical level. Despite recent progress in molecular design and engineering on single fluorophores, a systematic methodology to obtain multicolor emission in aggregated or solid states, which gives rise to practical implications, remains scarce. In this study, we present a general strategy to continuously tune the emission color of a single-fluorophore aggregate by polymerization-mediated through-space charge transfer (TSCT). Using a library of well-defined styrenic donor (D) polymers grown from an acceptor (A) fluorophore by controlled radical polymerization, we found that the solid-state emission color can be fine-tuned by varying three molecular parameters: (i) the monomer substituent, (ii) the end groups of the polymer, and (iii) the polymer chain length. Experimental and theoretical investigations reveal that the color tunability originates from the structurally dependent TSCT process that regulates charge transfer energy.
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http://dx.doi.org/10.1126/sciadv.abd1794DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8026123PMC
April 2021

Relative efficacy of veria and mastoidectomy techniques of cochlear implantation in preservation of sound-induced saccular responses.

Int J Audiol 2021 Apr 2:1-9. Epub 2021 Apr 2.

Department of Audiology, All India Institute of Speech and Hearing, Mysuru, India.

Objective: Cochlear implantation (CI) is a safe technique to give hearing sensation to a person with hearing impairment. The present study aimed to compare the two surgical approaches of CI, mastoidectomy and veria, for their effects on saccular function assessed using cervical vestibular-evoked myogenic potential (cVEMP).

Design: Multiple group time series design.

Study Sample: The study included 63 children (3-8 years old) who underwent CI using veria technique ( = 20) and mastoidectomy approach ( = 43). The 500-Hz tone-burst evoked cVEMP were recorded on three occasions- a day before CI surgery, a day after the device switch-on and 4 months after the switch-on.

Results: The post-implant results revealed the absence of cVEMP in nearly 40% of the participants. The amplitudes were significantly lower at the time of the switch-on and at the 4-months follow-up period ( < 0.05). Among the participants undergoing CI using mastoidectomy approach, amplitudes were significantly larger after surgery than those undergoing surgery using veria technique ( < 0.05).

Conclusions: The saccular responses are better preserved with the mastoidectomy technique than the veria technique for CI surgery.
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http://dx.doi.org/10.1080/14992027.2021.1905891DOI Listing
April 2021

Developmental toxicity of cadmium in infants and children: a review.

Environ Anal Health Toxicol 2021 Mar 4;36(1):e2021003-0. Epub 2021 Feb 4.

Forensic Science laboratory, Modinagar, Ghaziabad - 201204, India.

Several millions of people are exposed to cadmium worldwide due to natural and anthropogenic activities that led to their widespread distribution in the environment and have shown potential adverse effects on the kidneys, liver, heart and nervous system. Recently human and animal-based studies have been shown that In utero and early life exposure to cadmium can have serious health issues that are related to the risk of developmental disabilities and other outcomes in adulthood. Since, cadmium crosses the placental barrier and reaches easily to the fetus, even moderate or high-level exposure of this metal during pregnancy could be of serious health consequences which might be reflected either in the children's early or later stages of life. Mortality from various diseases including cancer, cardiovascular, respiratory, kidney and neurological problems, correlation with In utero or early life exposure to cadmium has been found in epidemiological studies. Animal studies with strong evidence of various diseases mostly support for the human studies, as well as suggested a myriad mechanism by which cadmium can interfere with human health and development. More studies are needed to establish the mechanism of cadmium-induced toxicity with environmentally relevant doses in childhood and later life. In this review, we provide a comprehensive examination of the literature addressing potential long- term health issues with In utero and early life exposure to cadmium, as well as correlating with human and animal exposure studies.
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http://dx.doi.org/10.5620/eaht.2021003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8207007PMC
March 2021

Primary Mediastinal B Cell Lymphoma: A Limited Institutional Experience with Uniform DAEPOCH-R Protocol.

Indian J Hematol Blood Transfus 2021 Jan 5;37(1):176-178. Epub 2020 Jun 5.

Department of Pathology, All India Institute of Medical Sciences (AIIMS), New Delhi, New Delhi, India.

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http://dx.doi.org/10.1007/s12288-020-01301-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7900323PMC
January 2021

Safety and Efficacy of Bendamustine-Rituximab in Treatment Naïve Symptomatic Follicular Lymphoma: An Institutional Analysis.

Indian J Hematol Blood Transfus 2021 Jan 9;37(1):169-170. Epub 2020 Jun 9.

Department of Pathology, All India Institute of Medical Sciences, New Delhi, India.

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http://dx.doi.org/10.1007/s12288-020-01294-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7900301PMC
January 2021

Co-morbid conditions in COVID-19 patients in Uttarakhand state of India.

J Glob Health 2021 Feb 15;11:03029. Epub 2021 Feb 15.

Department of Biotechnology, Hemvati Nandan Bahuguna Garhwal University, Srinagar (Garhwal), Uttarakhand, India.

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http://dx.doi.org/10.7189/jogh.11.03029DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7914403PMC
February 2021

Common Treatment, Common Variant: Evolutionary Prediction of Functional Pharmacogenomic Variants.

J Pers Med 2021 Feb 16;11(2). Epub 2021 Feb 16.

Coriell Institute for Medical Research, Camden, NJ 08003, USA.

Pharmacogenomics holds the promise of personalized drug efficacy optimization and drug toxicity minimization. Much of the research conducted to date, however, suffers from an ascertainment bias towards European participants. Here, we leverage publicly available, whole genome sequencing data collected from global populations, evolutionary characteristics, and annotated protein features to construct a new in silico machine learning pharmacogenetic identification method called XGB-PGX. When applied to pharmacogenetic data, XGB-PGX outperformed all existing prediction methods and identified over 2000 new pharmacogenetic variants. While there are modest pharmacogenetic allele frequency distribution differences across global population samples, the most striking distinction is between the relatively rare putatively neutral pharmacogene variants and the relatively common established and newly predicted functional pharamacogenetic variants. Our findings therefore support a focus on individual patient pharmacogenetic testing rather than on clinical presumptions about patient race, ethnicity, or ancestral geographic residence. We further encourage more attention be given to the impact of common variation on drug response and propose a new 'common treatment, common variant' perspective for pharmacogenetic prediction that is distinct from the types of variation that underlie complex and Mendelian disease. XGB-PGX has identified many new pharmacovariants that are present across all global communities; however, communities that have been underrepresented in genomic research are likely to benefit the most from XGB-PGX's in silico predictions.
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http://dx.doi.org/10.3390/jpm11020131DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7919641PMC
February 2021

The genome sequence of reveals adaptive evolution of drought tolerance mechanisms.

iScience 2021 Feb 21;24(2):102079. Epub 2021 Jan 21.

MetaBioSys Group, Department of Biological Sciences, Indian Institute of Science Education and Research Bhopal, Bhopal, Madhya Pradesh, India.

is a species from Asphodelaceae family having characteristics like drought resistance and numerous medicinal properties. However, the genetic basis of these phenotypes is yet unknown primarily due to unavailability of its genome sequence. Thus, we report the first genome sequence comprising of 12.93 Gbp and harboring 86,177 protein-coding genes. It is the first genome from Asphodelaceae family and the largest angiosperm genome sequenced and assembled till date. We also report the first genome-wide phylogeny of monocots including to resolve its phylogenetic position. The comprehensive comparative analysis of with other available high-quality monocot genomes revealed adaptive evolution in several genes of drought stress response, CAM pathway, and circadian rhythm and positive selection in DNA damage response genes in . This study provides clues on the genetic basis of evolution of drought stress tolerance capabilities of .
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http://dx.doi.org/10.1016/j.isci.2021.102079DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7889978PMC
February 2021
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