Publications by authors named "Paul D"

1,750 Publications

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Editorial: Advances in Microbial Biofuel Production.

Front Microbiol 2021 28;12:746216. Epub 2021 Sep 28.

Department of Biotechnology, School of Basic Sciences, Indian Institute of Information Technology, Una, India.

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http://dx.doi.org/10.3389/fmicb.2021.746216DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8506158PMC
September 2021

Phytoglobin-NO cycle and AOX pathway play a role in anaerobic germination and growth of deepwater rice.

Plant Cell Environ 2021 Oct 11. Epub 2021 Oct 11.

National Institute for Plant Genome Research, New Delhi, India.

An important and interesting feature of rice is that it can germinate under anoxic conditions. Though several biochemical adaptive mechanisms play an important role in the anaerobic germination of rice but the role of phytoglobin-nitric oxide cycle and alternative oxidase pathway is not known, therefore in this study we investigated the role of these pathways in anaerobic germination. Under anoxic conditions, deepwater rice germinated much higher and rapidly than aerobic condition and the anaerobic germination and growth were much higher in the presence of nitrite. The addition of nitrite stimulated NR activity and NO production. Important components of phytoglobin-NO cycle such as methaemoglobin reductase activity, expression of Phytoglobin1, NIA1 were elevated under anaerobic conditions in the presence of nitrite. The operation of phytoglobin-NO cycle also enhanced anaerobic ATP generation, LDH, ADH activities and in parallel ethylene levels were also enhanced. Interestingly nitrite suppressed the ROS production and lipid peroxidation. The reduction of ROS was accompanied by enhanced expression of mitochondrial alternative oxidase protein and its capacity. Application of AOX inhibitor SHAM inhibited the anoxic growth mediated by nitrite. In addition, nitrite improved the submergence tolerance of seedlings. Our study revealed that nitrite driven phytoglobin-NO cycle and AOX are crucial players in anaerobic germination and growth of deepwater rice.
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http://dx.doi.org/10.1111/pce.14198DOI Listing
October 2021

Prognostic factor for recurrence in esophagus cancer patients who underwent surgery for curative intent: A single-institution analysis.

J Cancer Res Ther 2021 Oct 1. Epub 2021 Oct 1.

Department of Medical Oncology, DMCH cancer center, Ludhiana, Punjab, India.

Objective: The purpose of this study is to analyze predisposing factors for a higher risk of recurrence in esophageal cancer patient who underwent surgery for curative intent and to do survival analysis of prognostic factors.

Materials And Methods: Between February 2018 and March 2020, we retrospectively identified 28 cases staged T1b to T4a managed electively at our institute as per multidisciplinary management plan. Demographic, clinical, radiological, operative, histopathological parameters, upfront surgery done or not, type of preoperative, and adjuvant treatment used and whether neoadjuvant or adjuvant therapy was planned along with waiting time for surgery, were assessed as potential risk factors. End point of study was to find potential risk factors for recurrence and to do their subgroup survival analysis.

Results: The recurrence rate in our study was 25% with a mean follow-up of 24 months. The median time of recurrence was 8.5 months, all recurrence occurred within 1 year. Overall DFS at 2 years was 72%. On univariate analysis, following prognostic factors were associated with high risk of recurrence, male sex X (1) =4.42, p = 0.035; histology subtype of adenocarcinoma X (1) = 7.07, p = 0.008; margin positive X (1) =3.76, p = 0.05; presence of lymph vascular invasion (LVI) X (1) =7.88, p = 0.005; presence of perineural invasion (PNI) X (1) =5.97, p = 0.015; postoperative T size >4 cm X (1) =3.86, p = 0.049; and nodal positivity X (3) =13.47, p = 0.004.

Conclusions: Male sex, adenocarcinoma histological subtype, positive resected margin, presence of LVI and PNI, postoperative T size >4 cm, and high postoperative nodal positivity and whether neoadjuvant versus adjuvant therapy given (on K. M analysis) were the identified predictors of recurrence which compromised DFS.
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http://dx.doi.org/10.4103/jcrt.JCRT_1702_20DOI Listing
October 2021

Ileal endometriosis: a rare cause of small bowel obstruction in the virgin abdomen.

ANZ J Surg 2021 Sep 29. Epub 2021 Sep 29.

Colorectal Unit, Dandenong Hospital, Monash Health, Melbourne, Victoria, Australia.

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http://dx.doi.org/10.1111/ans.17243DOI Listing
September 2021

Performance evaluation of automated chemiluminescence immunoassay based antigen detection - Moving towards more reliable ways to predict SARS-CoV-2 infection.

J Virol Methods 2021 12 22;298:114299. Epub 2021 Sep 22.

Department of Clinical Virology, Institute of Liver & Biliary Sciences, New Delhi, India. Electronic address:

Real-time reverse transcription- polymerase chain reaction (RT-PCR) has been the most reliable armoury for the diagnosis of COVID-19, considered to be the reference standard but fails to reproduce the correct predictability about the infectivity of the disease every time. Antigen detection however puts foothold in this aspect even though lacks in sensitivity, especially conventional Rapid Antigen Tests (RATs). Recently developed Chemiluminescence Immunoassay (CLIA) based antigen detection tests are promising and displayed better sensitivity. In the current study we have evaluated VITROS® SARS-CoV-2 Ag Test CLIA Kit, which was tested on 148 patient's samples attended to a tertiary care centre for testing of SARS-CoV-2. The performance of the kit was evaluated in comparison to RT-PCR and RAT and found to be a good test for antigen detection, best within the first few days of infection. The test has shown sensitivity of 94.3 % and specificity of 100 % in samples with corresponding Ct values of ≤25 by RT-PCR, which corresponds to high viral load and can predict ability of spreading the disease by the patients. With the results being semiquantitative along with improved sensitivity it can replace RATs for antigen detection for screening, provided good laboratory set up is included under consideration.
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http://dx.doi.org/10.1016/j.jviromet.2021.114299DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8457631PMC
December 2021

Syndromic approach to SARS-CoV-2 detection using QIAstat-Dx SARS-CoV-2 panel from clinical samples.

J Virol Methods 2021 12 22;298:114300. Epub 2021 Sep 22.

Department of Clinical Virology, Institute of Liver & Biliary Sciences, New Delhi, India. Electronic address:

The QIAstat-Dx SARS-CoV-2 panel is a multiplex cartridge based assay based on real time PCR which can detect 17 respiratory viruses, including the novel coronavirus SARS-CoV-2. A syndromic approach is the need of the hour for COVID-19 diagnostics among patients presenting with respiratory symptoms. The present study was done to evaluate 120 archived respiratory clinical specimens for SARS-CoV-2 on the SARS-CoV-2 panel. Further, 27 specimens were tested for other respiratory viruses, in comparison with the BioFire RP1.7 platform. The sensitivity and specificity for SARS-CoV-2 on SARS panel was found to be 90.00 % and 100 % respectively, indicating good diagnostic accuracy. The positive predictive value was found to be 100 %, negative predictive value was found to be 99.93 % and accuracy was 99.93 %. Detection of other respiratory viruses observed a concordance of 77.7 %. Despite advantages of speed, minimal expertise and accurate results; significant costs and discrepancies at Ct >35 remain important limitations of the SARS panel.
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http://dx.doi.org/10.1016/j.jviromet.2021.114300DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8457645PMC
December 2021

Liberating host-virus knowledge from biological dark data.

Lancet Planet Health 2021 10 23;5(10):e746-e750. Epub 2021 Sep 23.

Plazi, Bern, Switzerland.

Connecting basic data about bats and other potential hosts of SARS-CoV-2 with their ecological context is crucial to the understanding of the emergence and spread of the virus. However, when lockdowns in many countries started in March, 2020, the world's bat experts were locked out of their research laboratories, which in turn impeded access to large volumes of offline ecological and taxonomic data. Pandemic lockdowns have brought to attention the long-standing problem of so-called biological dark data: data that are published, but disconnected from digital knowledge resources and thus unavailable for high-throughput analysis. Knowledge of host-to-virus ecological interactions will be biased until this challenge is addressed. In this Viewpoint, we outline two viable solutions: first, in the short term, to interconnect published data about host organisms, viruses, and other pathogens; and second, to shift the publishing framework beyond unstructured text (the so-called PDF prison) to labelled networks of digital knowledge. As the indexing system for biodiversity data, biological taxonomy is foundational to both solutions. Building digitally connected knowledge graphs of host-pathogen interactions will establish the agility needed to quickly identify reservoir hosts of novel zoonoses, allow for more robust predictions of emergence, and thereby strengthen human and planetary health systems.
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http://dx.doi.org/10.1016/S2542-5196(21)00196-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8457912PMC
October 2021

Serum zinc level and its association with multidrug-resistant tuberculosis.

Int J Mycobacteriol 2021 Apr-Jun;10(2):177-181

Department of Public Health and Informatics, Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh.

Background: Zinc deficiency is evident in chronic diseases, but little is known about its association with multi-drug resistant tuberculosis (MDRTB). We aimed to measure serum zinc level in MDRTB patients and explore its association with MDRTB compared to drug-sensitive tuberculosis (DSTB).

Methods: We recruited 107 MDRTB and 87 DSTB patients from a tuberculosis referral hospital in Bangladesh. After overnight fasting, 5 ml venous blood was collected from each patient to measure serum zinc level through graphite furnace atomic absorption spectrophotometry method. Multivariate logistic regression was done to measure its association with MDRTB.

Results: The mean age of all patients was 36 years, where 70% were male. About 27% MDRTB patients and 2.3% DSTB patients had low serum zinc level (P < 0.0001). An inverse correlation was observed between serum zinc level and duration of anti-TB therapy (r-value: -0.252, P < 0.01). Reduced serum zinc level (odds ratio, 0.957; 95% confidence interval 0.923-0.992) was found as a significant associating factor for MDRTB after adjusted with age, sex, occupation, residence, tobacco consumption, Bacillus Calmette-Guérin-vaccination, and duration of anti-TB therapy.

Conclusion: A lower serum zinc level is significantly associated with MDRTB. The tuberculosis control program should address this in the MDRTB control strategy.
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http://dx.doi.org/10.4103/ijmy.ijmy_67_21DOI Listing
October 2021

Isolation and identification of carotenoid-producing yeast and evaluation of antimalarial activity of the extracted carotenoid(s) against P. falciparum.

Biol Futur 2021 Sep 19;72(3):325-337. Epub 2021 Mar 19.

Amity Institute of Biotechnology, Amity University, Uttar Pradesh (AUUP), Noida, 201313, India.

Plasmodial resistance to a variety of plant-based antimalarial drugs has led toward the discovery of more effective antimalarial compounds having chemical or biological origin. Since natural compounds are considered as safer drugs, in this study, yeast strains were identified and compared for the production of carotenoids that are well-known antioxidants and this metabolite was tested for its antiparasitic activity. Plasmodium falciparum 3D7 strain was selected as the target parasite for evaluation of antimalarial activity of yeast carotenoids using in vitro studies. Data were analyzed by FACS (fluorescence-activated cell sorter) and counted via gold standard Giemsa-stained smears. The extracted yeast carotenoids showed a profound inhibitory effect at a concentration of 10 µg/µl and 10 µg/µl when compared to β- carotene as control. SYBR Green1 fluorescent dye was used to confirm the decrease in parasitaemia at given range of concentration. Egress assay results suggested that treated parasite remained stalled at schizont stage with constricted morphology and were darkly stained. Non-toxicity of carotenoids on erythrocytes and on human liver hepatocellular carcinoma cells (HepG2 cells) was shown at a given concentration. This report provides strong evidence for antimalarial effects of extracted yeast carotenoids, which can be produced via a sustainable and cost-effective strategy and may be scaled up for industrial application.
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http://dx.doi.org/10.1007/s42977-021-00081-5DOI Listing
September 2021

Biologia Futura: use of biocides during COVID-19-global reshuffling of the microbiota.

Biol Futur 2021 Sep 1;72(3):273-280. Epub 2021 Feb 1.

Central Research Facility, Indian Institute of Technology Kharagpur, Kharagpur, 721302, India.

Aim The article reviews the current usage of biocides during this lockdown period for sanitizing our living areas due to the pandemic and discusses the pros and cons. Subject COVID-19 spread like wildfire to over 200 countries of the world across all continents. The causative agent, novel coronavirus (SARS-CoV-2) is being counter attacked by a thorough application of disinfectants and sterilants. However, the virus mutated over 30 times during this global pandemic, creating panic and leading to enhanced pathogenicity and consequently to more stringent sanitation measures for controlling it. However, excessive use of different types of biocides for disinfecting surfaces is highly alarming in several cases. Extensive application of biocides affects the microbial flora, leading to an abrupt decrease in the number and diversity of beneficial microbes that may directly affect the functioning of nutrient cycles. Results The increased concentration of biocides in agricultural land via surface water or pond water indirectly affect the soil and water ecosystem, soil aggregation and fertility. This will also lead to the flourishing of resistant strains due to loss of competition from the other species, which fail to persist after prolonged use of biocides. Conclusion It is necessary to realize the environmental impacts of biocides and sterilants. It is the right time to stop their entry into the agricultural ecosystem by following adequate management strategies and complete neutralization.
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http://dx.doi.org/10.1007/s42977-021-00069-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7848239PMC
September 2021

Identification of tyrosine kinase inhibitors from Panax bipinnatifidus and Panax pseudoginseng for RTK-HER2 and VEGFR2 receptors, by in silico approach.

Mol Divers 2021 Sep 23. Epub 2021 Sep 23.

Department of Biotechnology, National Institute of Technology Arunachal Pradesh, Yupia, Papum Pare, Arunachal Pradesh, 791112, India.

Breast and stomach cancer is reported as a leading cause for human mortality across the world. The overexpression of receptor tyrosine kinase (RTK) proteins, namely the human epidermal growth factor receptor2 (HER2) and the vascular endothelial growth factor receptor2 (VEGFR2), is reported to be responsible for development and metastasis of breast and stomach cancer. Although several synthetic tyrosine kinase inhibitors (TKIs) as drug candidates targeting RTK-HER2 and VEGFR2 are currently available in the market, these are expensive with the reported side effects. This confers an opportunity for development of alternative novel tyrosine kinase inhibitors (TKIs) for RTK-HER2 and VEGFR2 receptors from the botanical sources. In the present study, we characterized 47 bioactive phytocompounds from the methanol extracts of the rhizomes of Asiatic traditional medicinal herbs-Panax bipinnatifidus and Panax pseudoginseng, of Indian Himalayan landraces using HPLC, GC-MS and high-sensitivity LC-MS tools. We performed molecular docking and molecular dynamics simulation analysis using Schrödinger suite 2020-3 to confirm the TKI phytocompounds showing the best binding affinity towards RTK-HER2 and VEGFR2 receptors. The results of molecular docking studies confirmed that the phytocompound (ligand) luteolin 7-O-glucoside (IHP15) showed the highest binding affinity towards receptor HER2 (PDB ID: 3PP0) with docking score and Glide g score (G-Score) of - 13.272, while chlorogenic acid (IHP12) showed the highest binding affinity towards receptor VEGFR2 (PDB ID: 4AGC) with docking score and Glide g score (G-Score) of - 10.673. Molecular dynamics (MD) simulation analysis carried out for 100 ns has confirmed strong binding interaction between the ligand and receptor complex [luteolin 7-O-glucoside (IHP15) and HER2 (PDB ID: 3PP0)] and is found to be stabilized within 40 to 100 ns of MD simulation, whereas ligand-receptor complex [chlorogenic acid (IPH12) and VEGFR2 (PDB ID: 4AGC)] also showed strong binding interaction and is found to be stabilized within 18-30 ns but slightly deviated during 100 ns of MD simulation. In silico ADME-Tox study using SwissADME revealed that the ligands luteolin 7-O-glucoside (IHP15) and chlorogenic acid (IHP12) have passed majority parameters of the common drug discovery rules. The present study has confirmed luteolin 7-O-glucoside (IHP15) and chlorogenic acid (IHP12) as potential tyrosine kinase inhibitors (TKIs) which were found to inhibit RTKs-HER2 and VEGFR2 receptor proteins, and thus paving the way for development of alternative potential TKIs (drug molecules) for treatment of HER2- and VEGFR2-positive breast and stomach cancer.
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http://dx.doi.org/10.1007/s11030-021-10304-5DOI Listing
September 2021

Faceting of Si and Ge crystals grown on deeply patterned Si substrates in the kinetic regime: phase-field modelling and experiments.

Sci Rep 2021 Sep 22;11(1):18825. Epub 2021 Sep 22.

L-NESS and Department of Materials Science, University of Milano - Bicocca, 20125, Milan, Italy.

The development of three-dimensional architectures in semiconductor technology is paving the way to new device concepts for various applications, from quantum computing to single photon avalanche detectors. In most cases, such structures are achievable only under far-from-equilibrium growth conditions. Controlling the shape and morphology of the growing structures, to meet the strict requirements for an application, is far more complex than in close-to-equilibrium cases. The development of predictive simulation tools can be essential to guide the experiments. A versatile phase-field model for kinetic crystal growth is presented and applied to the prototypical case of Ge/Si vertical microcrystals grown on deeply patterned Si substrates. These structures, under development for innovative optoelectronic applications, are characterized by a complex three-dimensional set of facets essentially driven by facet competition. First, the parameters describing the kinetics on the surface of Si and Ge are fitted on a small set of experimental results. To this goal, Si vertical microcrystals have been grown, while for Ge the fitting parameters have been obtained from data from the literature. Once calibrated, the predictive capabilities of the model are demonstrated and exploited for investigating new pattern geometries and crystal morphologies, offering a guideline for the design of new 3D heterostructures. The reported methodology is intended to be a general approach for investigating faceted growth under far-from-equilibrium conditions.
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http://dx.doi.org/10.1038/s41598-021-98285-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8458435PMC
September 2021

Thrombocytopenia in COVID-19: Focused Summary of Current Understanding of Mechanisms and Clinical Implications.

J Pediatr Hematol Oncol 2021 10;43(7):243-248

Medical Oncology, Dayanand Medical College, Ludhiana, Punjab, India.

Thrombocytopenia is noted in corona virus disease-2019 (COVID-19) with a prevalence of 5% to 41%, and has been observed to be associated with inferior outcomes. The pathogenesis of thrombocytopenia in COVID-19 is unique and differs from other viral syndromes in terms of clinical presentation and causative mechanisms. Platelets act as both targets and the initial defense against severe acute respiratory syndrome-coronavirus 2 and work in concert with the underlying thrombophilic mechanisms to modulate the final disease phenotype. Understanding these mechanisms may possibly allow targeting of a key component of COVID-19 pathogenesis. We provide a focused review of the current mechanisms implicated in development of thrombocytopenia in COVID-19 and therapeutic implications of the same.
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http://dx.doi.org/10.1097/MPH.0000000000002264DOI Listing
October 2021

Risk Factors of Biochemical Failure in Locally Advanced Carcinoma Prostate Treated With Definitive External Beam Radiotherapy and Androgen Deprivation Therapy: Experience From Tertiary Care Center in North India.

Cureus 2021 Aug 4;13(8):e16895. Epub 2021 Aug 4.

Oncology, Dayanand Medical College & Hospital (DMCH), Ludhiana, IND.

Background Locally advanced prostate cancer (LACAP), despite external beam radiotherapy (EBRT) along with antiandrogen therapy (ADT) has risk of prostate-specific antigen (PSA) progression. Furthermore, number of studies have emphasized on different prognostic factors. The purpose of our study is to analyze risk factors for biochemical failure (BF) in these patients treated at our institute. Methods Our study is a single-institution retrospective observational done at a tertiary care center in North India. Between January 2018 and December 2020, we retrospectively identified 34 patients managed at our institute as per multidisciplinary board (MBD). Demographic, clinical, radiological, pathological and treatment-related parameters were assessed as potential risk factors. End-point of the study was to find significant risk factors for BF. Statistical analysis was done on SPSS, version 20 (IBM Corp., Armonk, NY). Results All eligible patients received EBRT with ADT as per institution policy. Mean follow-up period was 20 months during which two (5.9%) patients had BF at a mean of 30 months after EBRT. Four-year PSA-progression-free survival rate was 73%. On univariate analysis, prognostic factors associated with high risk of BF were Gleason score and clinical T stage. Conclusion In summary, prognostic factors for high risk of BF leading to clinical progression are Gleason score 9 or 10 and clinical T3b stage.
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http://dx.doi.org/10.7759/cureus.16895DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8412057PMC
August 2021

An automated method for thermal-optical separation of aerosol organic/elemental carbon for C analysis at the sub-μgC level: A comprehensive assessment.

Sci Total Environ 2021 Sep 1;804:150031. Epub 2021 Sep 1.

Centre for Isotope Research (CIO), Energy and Sustainability Research Institute Groningen (ESRIG), University of Groningen, Groningen 9747AG, the Netherlands. Electronic address:

We describe and thoroughly evaluate a method for C analysis in different fractions of carbonaceous aerosols, especially elemental carbon (EC). This method combines a Sunset thermal-optical analyzer and an isotope ratio mass spectrometer (IRMS) via a custom-built automated separation, purification, and injection system. Organic carbon (OC), EC, and other specific fractions from aerosol filter samples can be separated and analyzed automatically for C based on thermal-optical protocols (EUSAAR_2 in this study) at sub-μgC levels. The main challenges in isolating EC for C analysis are the possible artifacts during OC/EC separation, including the premature loss of EC and the formation of pyrolyzed OC (pOC) that is difficult to separate from EC. Since those artifacts can be accompanied with isotope fractionation, their influence on the stable isotopic composition of EC was comprehensively investigated with various test compounds. The results show that the thermal-optical method is relatively successful in OC/EC separation for C analysis. The method was further tested on real aerosols samples. For biomass-burning source samples, (partial) inclusion of pOC into EC has negligible influence on the C signature of EC. However, for ambient samples, the influence of pOC on the C signature of EC can be significant, if it is not well separated from EC, which is true for many current methods for measuring C on EC. A case study in Xi'an, China, where pOC is enriched in C compared to EC, shows that this can lead to an overestimate of coal and an underestimate of traffic emissions in isotope-based source apportionment.
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http://dx.doi.org/10.1016/j.scitotenv.2021.150031DOI Listing
September 2021

Genome-wide analysis of blood lipid metabolites in over 5000 South Asians reveals biological insights at cardiometabolic disease loci.

BMC Med 2021 09 10;19(1):232. Epub 2021 Sep 10.

Core Metabolomics and Lipidomics Laboratory, National Institute for Health Research, Cambridge Biomedical Research Centre, Cambridge, CB2 0QQ, UK.

Background: Genetic, lifestyle, and environmental factors can lead to perturbations in circulating lipid levels and increase the risk of cardiovascular and metabolic diseases. However, how changes in individual lipid species contribute to disease risk is often unclear. Moreover, little is known about the role of lipids on cardiovascular disease in Pakistan, a population historically underrepresented in cardiovascular studies.

Methods: We characterised the genetic architecture of the human blood lipidome in 5662 hospital controls from the Pakistan Risk of Myocardial Infarction Study (PROMIS) and 13,814 healthy British blood donors from the INTERVAL study. We applied a candidate causal gene prioritisation tool to link the genetic variants associated with each lipid to the most likely causal genes, and Gaussian Graphical Modelling network analysis to identify and illustrate relationships between lipids and genetic loci.

Results: We identified 253 genetic associations with 181 lipids measured using direct infusion high-resolution mass spectrometry in PROMIS, and 502 genetic associations with 244 lipids in INTERVAL. Our analyses revealed new biological insights at genetic loci associated with cardiometabolic diseases, including novel lipid associations at the LPL, MBOAT7, LIPC, APOE-C1-C2-C4, SGPP1, and SPTLC3 loci.

Conclusions: Our findings, generated using a distinctive lipidomics platform in an understudied South Asian population, strengthen and expand the knowledge base of the genetic determinants of lipids and their association with cardiometabolic disease-related loci.
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http://dx.doi.org/10.1186/s12916-021-02087-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8431908PMC
September 2021

The anthropometric assessment of body composition and nutritional status in children aged 2-15 years: A cross-sectional study from three districts in Bangladesh.

PLoS One 2021 9;16(9):e0257055. Epub 2021 Sep 9.

Department of Applied Nutrition and Food Technology, Islamic University, Kushtia, Bangladesh.

Background: Early life nutrition plays a critical role in the development of better health and nutrition in adulthood. However, assessing the nutritional status of Bangladeshi children and adolescents through measurement of body composition using skinfold thickness is barely studied. The current study aims to determine children's body composition and nutritional status, and contributing factors among children aged 2 to 15 years in the northern part of Bangladesh.

Methods: This is a descriptive cross-sectional study done in Bangladesh. Anthropometric methods, including multiple skinfold thickness and basic anthropometric and socio-demographic characteristics, were used. Body composition was calculated from multiple skinfold thicknesses using the standard regression equation. Nutritional status was measured using Z score according to WHO 2007 reference standard. A total of 330 children from Naogaon, Bogra and Kurigram districts in Bangladesh were examined from April 2019 to September 2019.

Results: The Nutritional status of 2-15 years old child is exceedingly poor in the northern part of Bangladesh. Fat mass and fat-free mass were higher among children from Kurigram district than from Bogra and Naogaon district. Body fat percentages and arm fat area were greater among female children than males. The overall prevalence of stunting, underweight and wasting was around 25%, 32% and 29%, respectively, and the rate was higher among girls and children aged 2-5 years. The average SD score for weight-for-age, height-for-age, and BMI-for-age was -1.295, -0.937 and -1.009. The median weight-for-age and height-for-age Z scores of boys and girls were below the WHO reference percentile rank. Girls were twice (OR:1.951, CI:1.150-3.331) as likely to suffer from being underweight than boys. Children who don't practice handwashing are three times (OR:3.531, CI:1.657-7.525) more likely to be underweight. Children become underweight and stunted when their family income is not sufficient to maintain their nutritional requirements.

Conclusions: The children of the three northern districts had a poor nutritional status, and family income was the potential contributing factor. Therefore, interventions like the promotion of income-generating activities and integrated approaches to ensuring food diversification could be an option to address the nutritional problem of children of the three northern districts of Bangladesh.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0257055PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8428712PMC
September 2021

Techno-economic process modelling and Monte Carlo simulation data of uncertainty quantification in field-grown plant-based manufacturing.

Data Brief 2021 Oct 21;38:107317. Epub 2021 Aug 21.

Department of Chemical Engineering, University of California, Davis, CA, USA.

This data article is related to the research article, M.J. McNulty, K. Kelada, D. Paul, S. Nandi, and K.A. McDonald, Introducing uncertainty quantification to techno-economic models of manufacturing field-grown plant-made products, Food Bioprod. Process. 128 (2021) 153-165." The raw and analyzed data presented are related to generation, analysis, and optimization of ultra-large-scale field-grown plant-based manufacturing of high-value recombinant protein under uncertainty. The data have been acquired using deterministic techno-economic process model simulation in SuperPro Designer integrated with stochastic Monte Carlo-based simulation in Microsoft Excel using the Crystal Ball plug-in. The purpose of the article is to make techno-economic and associated uncertainty data available to be leveraged and adapted for other research purposes.
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http://dx.doi.org/10.1016/j.dib.2021.107317DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8405912PMC
October 2021

Cross-Sectional Design: Link Between Parkinson's Pain and Restless Leg Syndrome.

J Geriatr Psychiatry Neurol 2021 Sep 1:8919887211036188. Epub 2021 Sep 1.

Rouge Valley Hospital, Toronto, Ontario, Canada.

Objective: Prior research suggests that restless leg syndrome (RLS) is prevalent in Parkinson's disease (PD) with insufficient evidence to support the relationship between RLS, PD, and pain. This study explored the relationship between pain in PD patients and its association with the prevalence and severity of RLS.

Method: 127 PD patients were assessed for PD and RLS using the U.K. Brain bank Criteria and the Restless Leg Syndrome diagnostic criteria, respectively. These patients were also assessed for pain perception and interference using the Brief Pain Inventory.

Results: The results demonstrated Parkinson's disease patients who reported pain scored 23 more Restless Leg Syndrome prevalence points ( < 0.05), and 8.5 counts higher for Restless Leg Syndrome severity ( < 0.05) compared to the group of Parkinson's disease patients denying pain.

Discussion: The presence of pain in PD patients indicated a higher RLS prevalence and an increased RLS severity. This finding suggests patients suffering from pain interference may experience more severe RLS symptoms. This demonstrates an inextricable link and association between pain in PD patients and RLS. Further robust investigations are required to elucidate any potential causative links, which can inform more holistic treatment principles.
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http://dx.doi.org/10.1177/08919887211036188DOI Listing
September 2021

Representation of Women and Underrepresented Groups in US Academic Medicine by Specialty.

JAMA Netw Open 2021 Aug 2;4(8):e2123512. Epub 2021 Aug 2.

Department of Neurosurgery, University of Rochester Medical Center, Rochester, New York.

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http://dx.doi.org/10.1001/jamanetworkopen.2021.23512DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8406079PMC
August 2021

Impact of DNA sequences on DNA 'opening' by the Rad4/XPC nucleotide excision repair complex.

DNA Repair (Amst) 2021 Nov 29;107:103194. Epub 2021 Jul 29.

Department of Chemistry and Biochemistry, Baylor University, Waco, TX, 76798, USA. Electronic address:

Rad4/XPC recognizes diverse DNA lesions to initiate nucleotide excision repair (NER). However, NER propensities among lesions vary widely and repair-resistant lesions are persistent and thus highly mutagenic. Rad4 recognizes repair-proficient lesions by unwinding ('opening') the damaged DNA site. Such 'opening' is also observed on a normal DNA sequence containing consecutive C/G's (CCC/GGG) when tethered to Rad4 to prevent protein diffusion. However, it was unknown if such tethering-facilitated DNA 'opening' could occur on any DNA or if certain structures/sequences would resist being 'opened'. Here, we report that DNA containing alternating C/G's (CGC/GCG) failed to be opened even when tethered; instead, Rad4 bound in a 180°-reversed manner, capping the DNA end. Fluorescence lifetime studies of DNA conformations in solution showed that CCC/GGG exhibits local pre-melting that is absent in CGC/GCG. In MD simulations, CGC/GCG failed to engage Rad4 to promote 'opening' contrary to CCC/GGG. Altogether, our study illustrates how local sequences can impact DNA recognition by Rad4/XPC and how certain DNA sites resist being 'opened' even with Rad4 held at that site indefinitely. The contrast between CCC/GGG and CGC/GCG sequences in Rad4-DNA recognition may help decipher a lesion's mutagenicity in various genomic sequence contexts to explain lesion-determined mutational hot and cold spots.
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http://dx.doi.org/10.1016/j.dnarep.2021.103194DOI Listing
November 2021

Multi-scale network targeting: A holistic systems-biology approach to cancer treatment.

Prog Biophys Mol Biol 2021 Oct 21;165:72-79. Epub 2021 Aug 21.

Department of Mathematics, University of California Irvine, Irvine, CA, 92697, USA. Electronic address:

The vulnerabilities of cancer at the cellular and, recently, with the introduction of immunotherapy, at the tissue level, have been exploited with variable success. Evaluating the cancer system vulnerabilities at the organismic level through analysis of network topology and network dynamics can potentially predict novel anti-cancer drug targets directed at the macroscopic cancer networks. Theoretical work analyzing the properties and the vulnerabilities of the multi-scale network of cancer needs to go hand-in-hand with experimental research that uncovers the biological nature of the relevant networks and reveals new targetable vulnerabilities. It is our hope that attacking cancer on different spatial scales, in a concerted integrated approach, may present opportunities for novel ways to prevent treatment resistance.
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http://dx.doi.org/10.1016/j.pbiomolbio.2021.08.004DOI Listing
October 2021

One Gene, Many Facets: Multiple Immune Pathway Dysregulation in SOCS1 Haploinsufficiency.

Front Immunol 2021 5;12:680334. Epub 2021 Aug 5.

Cambridge Institute of Therapeutic Immunology and Infectious Disease, Jeffrey Cheah Biomedical Centre, University of Cambridge, Cambridge, United Kingdom.

Background: Inborn errors of immunity (IEI) present with a large phenotypic spectrum of disease, which can pose diagnostic and therapeutic challenges. Suppressor of cytokine signaling 1 (SOCS1) is a key negative regulator of cytokine signaling, and has recently been associated with a novel IEI. Of patients described to date, it is apparent that haploinsufficiency has a pleiotropic effect in humans.

Objective: We sought to investigate whether dysregulation of immune pathways, in addition to STAT1, play a role in the broad clinical manifestations of haploinsufficiency.

Methods: We assessed impacts of reduced expression across multiple immune cell pathways utilizing patient cells and CRISPR/Cas9 edited primary human T cells.

Results: haploinsufficiency phenotypes straddled across the International Union of Immunological Societies classifications of IEI. We found that reduced SOCS1 expression led to dysregulation of multiple intracellular pathways in immune cells. STAT1 phosphorylation is enhanced, comparably with STAT1 gain-of-function mutations, and STAT3 phosphorylation is similarly reduced with concurrent reduction of Th17 cells. Furthermore, reduced SOCS1 E3 ligase function was associated with increased FAK1 in immune cells, and increased AKT and p70 ribosomal protein S6 kinase phosphorylation. We also found Toll-like receptor responses are increased in haploinsufficiency patients.

Conclusions: haploinsufficiency is a pleiotropic monogenic IEI. Dysregulation of multiple immune cell pathways may explain the variable clinical phenotype associated with this new condition. Knowledge of these additional dysregulated immune pathways is important when considering the optimum management for haploinsufficient patients.
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http://dx.doi.org/10.3389/fimmu.2021.680334DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8375263PMC
August 2021

Local Field Potential-Based Programming: A Proof-of-Concept Pilot Study.

Neuromodulation 2021 Aug 18. Epub 2021 Aug 18.

Krembil Brain Institute, University Health Network, Toronto, ON, Canada.

Objectives: Programming deep brain stimulation (DBS) is still based on a trial-and-error approach, often becoming a time-consuming process for both treating physicians and patients. Several strategies have been proposed to streamline DBS programming, most of which are preliminary and mainly address Parkinson's disease, a condition readily responsive to DBS adjustments. In the present proof-of-principle pilot study, we successfully demonstrate that local field potentials (LFP)-based programming can be an effective approach when used for DBS indications that have a delayed temporal onset of benefit.

Materials And Methods: A recently commercialized implantable pulse generator (IPG) with the capability to non-invasively and chronically stream live and/or record LFPs from DBS electrode after implantation was used to program one pediatric patient with generalized dystonia and an adult with seizures refractory to multiple medications and vagal nerve stimulation.

Results: The IPG survey function detected a peak in the delta range (1.95 Hz) in the left globus pallidus of first patient. This LFP was detected when recording in the brain area adjacent to contacts 9 and 10 and absent when recording from other areas. The chronic recording of the 1.95 Hz LFP with two sets of stimulation showed a greater power increase with the settings associated with a worsening of dystonia. Broadband LFP home recording of "absence seizure" and "focal/partial seizure" was used in the second patient and reviewer with the IPG "timeline" and "event" functions. The chronic recording of the 2.93 Hz and 8.79 Hz (spit sensing) showed a reduced power with the stimulation setting associated with seizure control.

Conclusions: The approach presented in this pilot proof-of-concept study may inform and streamline the DBS programming for conditions requiring clinicians and patients to wait weeks before appreciating any clinical benefit. Prospective studies on larger samples of patients are warranted.
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http://dx.doi.org/10.1111/ner.13520DOI Listing
August 2021

Mitigation of in-hospital risk of coronavirus disease 2019: Experience from a haematology-oncology and stem cell transplant setting.

Natl Med J India 2021 Jan-Feb;34(1):10-14

Department of Medical Oncology, Dayanand Medical College and Hospital, Ludhiana 141001, Punjab, India.

Background: . Coronavirus disease 2019 (Covid-19) was first described in December 2019 and has evolved into an ongoing global pandemic. Cancer patients on chemotherapy are immunocompromised and are at the highest risk of Covid-19-related complications. We describe our experience with the management of haematology-oncology and stem cell transplant (SCT) patients receiving curative chemotherapy in a hospital with a high influx of Covid-19 patients.

Methods: . We did a prospective observational study at a 99-bedded cancer centre of a tertiary care teaching hospital from April 2020 to September 2020. Preventive measures taken were categorized as follows: (i) staff: screening, mandatory use of personal protective equipment (PPE), risk stratification of potential exposure and testing and isolation as needed; (ii) patients: mandatory viral polymerase chain reaction testing, segregation of positive and untested patients and testing of family members; and (iii) environment: mandatory regular cleaning, visitor restriction, telemedicine services and reassignment of priority to clinic visits. Treatment of the underlying conditions was continued with added precautions.

Results: . A total of 54 patients were included in the analysis, including 48 with haematological malignancies and 6 for stem cell therapy. Preventive measures were universally applied, and chemotherapy with a curative intent was initiated as per protocol. Three patients were detected to have Covid-19 infection before admission and one after the institution of chemotherapy. Nine patients died after the first cycle of chemotherapy, 2 due to severe Covid-19-related illness and 7 due to complications of chemotherapy or disease progression.

Conclusions: . In the wake of the Covid-19 pandemic, treatment for haematological malignancies must continue while balancing the risk of Covid-19 infections. Our report emphasizes the effectiveness of measures such as hand hygiene, social isolation, patient segregation, use of masks and PPE and universal pre-treatment testing for Covid-19 in reducing the risk of infection in a high-risk clinical setting.
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http://dx.doi.org/10.4103/0970-258X.315901DOI Listing
August 2021

Use of Dental Bisphenol A-Glycidyl Methacrylate Composite to Repair Refractory Cerebrospinal Fluid Leaks Associated With Large-Scale Anterior Skull Base Defects.

J Craniofac Surg 2021 Jul-Aug 01;32(5):1805-1809

Department of Surgery, Faculty of Medicine and Biomedical Sciences, Yaounde Central Hospital, Yaounde, Cameroon.

Abstract: Treatment of refractory cerebrospinal fluid (CSF) leaks, particularly those associated with large skull base defects, is challenging. A variety of synthetic biomaterial-based systems have been investigated in experimental models and/or humans for reconstructing cranial base defects. A widely used dental composite (bisphenol A-glycidyl methacrylate [bis-GMA]) has been shown to be effective for reconstruction of anterior skull base defects in animal models. Here, we report 4 patients who underwent reconstruction of large anterior skull base defects (1405.8 ± 511 mm2) secondary to tumor resection and traumatic injury using the dental bis-GMA resin-based composite. A vascularized pericranial flap with fibrin glue was initially performed in all patients with concurrent use of dental bis-GMA during the primary surgery in 2 patients, and later use (in a repeat surgery) in other 2 cases. In these latter 2, CSF rhinorrhea persisted after the initial surgery (in the absence of bis-GMA use) despite external CSF drainage with lumbar drain. Following treatment with bis-GMA, rigid structural support and watertight closure of the defect were successfully achieved. At the follow-up, CSF leak did not recur and none of the patients had any complications related to the surgery or the composite. The results obtained from this series are promising, and dental bis-GMA resin seems to provide an effective and feasible material for the treatment and prevention of CSF leaks related to large-scale anterior skull base defects. However, further studies with longer clinical follow-up and larger number of patients are required to prove the safety and efficacy of this matrix in the long run.
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http://dx.doi.org/10.1097/SCS.0000000000007568DOI Listing
July 2021

Empty Sella Syndrome as a Window Into the Neuroprotective Effects of Prolactin.

Front Med (Lausanne) 2021 8;8:680602. Epub 2021 Jul 8.

Department of Neurosurgery, University of Rochester Medical Center, Rochester, NY, United States.

The goal of this study was to relate diffusion MR measures of white matter integrity of the retinofugal visual pathway with prolactin levels in a patient with downward herniation of the optic chiasm secondary to medical treatment of a prolactinoma. A 36-year-old woman with a prolactinoma presented with progressive bilateral visual field defects 9 years after initial diagnosis and medical treatment. She was diagnosed with empty-sella syndrome and instructed to stop cabergoline. Hormone testing was conducted in tandem with routine clinical evaluations over 1 year and the patient was followed with diffusion magnetic resonance imaging (dMRI), optical coherence tomography (OCT), and automated perimetry at three time points. Five healthy controls underwent a complementary battery of clinical and neuroimaging tests at a single time point. Shortly after discontinuing cabergoline, diffusion metrics in the optic tracts were within the range of values observed in healthy controls. However, following a brief period where the patient resumed cabergoline (of her own volition), there was a decrease in serum prolactin with a corresponding decrease in visual ability and increase in radial diffusivity ( < 0.001). Those measures again returned to their baseline ranges after discontinuing cabergoline a second time. These results demonstrate the sensitivity of dMRI to detect rapid and functionally significant microstructural changes in white matter tracts secondary to alterations in serum prolactin levels. The inverse relations between prolactin and measures of white matter integrity and visual function are consistent with the hypothesis that prolactin can play a neuroprotective role in the injured nervous system.
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http://dx.doi.org/10.3389/fmed.2021.680602DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8295462PMC
July 2021

Women's Rugby League: Positional Groups and Peak Locomotor Demands.

Front Sports Act Living 2021 29;3:648126. Epub 2021 Jun 29.

School of Science and Technology, University of New England, Armidale, NSW, Australia.

The aims of this study were to (a) use a data-based approach to identify positional groups within National Rugby League Women's (NRLW) match-play and (b) quantify the peak locomotor demands of NRLW match-play by positional groups. Microtechnology (Global Navigational Satellite System [GNSS] and integrated inertial sensors; = 142 files; = 76 players) and match statistics ( = 238 files; = 80 players) were collected from all NRLW teams across the 2019 season. Data-based clustering of match statistics was utilized to identify positional clusters through classifying individual playing positions into distinct positional groups. Moving averages (0.5, 1, 2, 3, 5, and 10 min) of peak running and average acceleration/deceleration demands were calculated via microtechnology data for each player per match. All analysis was undertaken in R (R Foundation for Statistical Computing) with positional differences determined via a linear mixed model and effect sizes (ES). Data-based clustering suggested that, when informed by match statistics, individual playing positions can be clustered into one of three positional groups. Based on the clustering of the individual positions, these groups could be broadly defined as backs (fullback, wing, and center), adjustables (halfback, five-eighth, and hooker), and forwards (prop, second-row, and lock). Backs and adjustables demonstrated greater running (backs: ES 0.51-1.00; < 0.05; adjustables: ES 0.51-0.74, < 0.05) and average acceleration/deceleration (backs: ES 0.48-0.87; < 0.05; adjustables: ES 0.60-0.85, < 0.05) demands than forwards across all durations. Smaller differences (small to trivial) were noted between backs and adjustables across peak running and average acceleration/deceleration demands. Such findings suggest an emerging need to delineate training programs in situations in which individual playing positions train in positional group based settings. Collectively, this work informs the positional groupings that could be applied when examining NRLW data and supports the development of a framework for specifically training female rugby league players for the demands of the NRLW competition.
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http://dx.doi.org/10.3389/fspor.2021.648126DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8276862PMC
June 2021

In Vivo Characterization of Endogenous Cardiovascular Extracellular Vesicles in Larval and Adult Zebrafish.

Arterioscler Thromb Vasc Biol 2021 09 15;41(9):2454-2468. Epub 2021 Jul 15.

School of Physiology, Pharmacology & Neuroscience, Faculty of Biomedical Sciences (A.S., M.B., C.T., J.L., D.P., R.J.R.).

Objective: Extracellular vesicles (EVs) facilitate molecular transport across extracellular space, allowing local and systemic signaling during homeostasis and in disease. Extensive studies have described functional roles for EV populations, including during cardiovascular disease, but the in vivo characterization of endogenously produced EVs is still in its infancy. Because of their genetic tractability and live imaging amenability, zebrafish represent an ideal but under-used model to investigate endogenous EVs. We aimed to establish a transgenic zebrafish model to allow the in vivo identification, tracking, and extraction of endogenous EVs produced by different cell types.

Approach And Results: Using a membrane-tethered fluorophore reporter system, we show that EVs can be fluorescently labeled in larval and adult zebrafish and demonstrate that multiple cell types including endothelial cells and cardiomyocytes actively produce EVs in vivo. Cell-type specific EVs can be tracked by high spatiotemporal resolution light-sheet live imaging and modified flow cytometry methods allow these EVs to be further evaluated. Additionally, cryo electron microscopy reveals the full morphological diversity of larval and adult EVs. Importantly, we demonstrate the utility of this model by showing that different cell types exchange EVs in the adult heart and that ischemic injury models dynamically alter EV production.

Conclusions: We describe a powerful in vivo zebrafish model for the investigation of endogenous EVs in all aspects of cardiovascular biology and pathology. A cell membrane fluorophore labeling approach allows cell-type specific tracing of EV origin without bias toward the expression of individual protein markers and will allow detailed future examination of their function.
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http://dx.doi.org/10.1161/ATVBAHA.121.316539DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8384253PMC
September 2021
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