Publications by authors named "Chowdhury S"

2,477 Publications

SyNC, a Computationally Extensive and Realistic Neural Net to Identify Relative Impacts of Synaptopathy Mechanisms on Glutamatergic Neurons and Their Networks in Autism and Complex Neurological Disorders.

Front Cell Neurosci 2021 20;15:674030. Epub 2021 Jul 20.

Independent Researcher, Kolkata, India.

Synaptic function and experience-dependent plasticity across multiple synapses are dependent on the types of neurons interacting as well as the intricate mechanisms that operate at the molecular level of the synapse. To understand the complexity of information processing at synaptic networks will rely in part on effective computational models. Such models should also evaluate disruptions to synaptic function by multiple mechanisms. By co-development of algorithms alongside hardware, real time analysis metrics can be co-prioritized along with biological complexity. The hippocampus is implicated in autism spectrum disorders (ASD) and within this region glutamatergic neurons constitute 90% of the neurons integral to the functioning of neuronal networks. Here we generate a computational model referred to as ASD interrogator (ASDint) and corresponding hardware to enable in silicon analysis of multiple ASD mechanisms affecting glutamatergic neuron synapses. The hardware architecture Synaptic Neuronal Circuit, SyNC, is a novel GPU accelerator or neural net, that extends discovery by acting as a biologically relevant realistic neuron synapse in real time. Co-developed ASDint and SyNC expand spiking neural network models of plasticity to comparative analysis of retrograde messengers. The SyNC model is realized in an ASIC architecture, which enables the ability to compute increasingly complex scenarios without sacrificing area efficiency of the model. Here we apply the ASDint model to analyse neuronal circuitry dysfunctions associated with autism spectral disorder (ASD) synaptopathies and their effects on the synaptic learning parameter and demonstrate SyNC on an ideal ASDint scenario. Our work highlights the value of secondary pathways in regard to evaluating complex ASD synaptopathy mechanisms. By comparing the degree of variation in the synaptic learning parameter to the response obtained from simulations of the ideal scenario we determine the potency and time of the effect of a particular evaluated mechanism. Hence simulations of such scenarios in even a small neuronal network now allows us to identify relative impacts of changed parameters and their effect on synaptic function. Based on this, we can estimate the minimum fraction of a neuron exhibiting a particular dysfunction scenario required to lead to complete failure of a neural network to coordinate pre-synaptic and post-synaptic outputs.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fncel.2021.674030DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8330424PMC
July 2021

Anthropogenic effects on the physiology and behaviour of chacma baboons in the Cape Peninsula of South Africa.

Conserv Physiol 2020 31;8(1):coaa066. Epub 2020 Jul 31.

Anthropology Program, Graduate Center, CUNY, New York, NY 10016, USA.

As animals increasingly occupy habitats in proximity to humans, with home ranges a mosaic of natural and anthropogenic landscapes, it becomes imperative from a conservation perspective to understand the impacts of human activities on wildlife. Many non-human primates share habitats with humans, an ability stemming largely from shared ecological needs due to our close evolutionary relationship. Such proximity, however, is often accompanied by direct conflict between humans and wildlife, leading to higher stress levels, injuries, mortality and behavioural changes, with detrimental effects on long-term health and fitness. Glucocorticoid (GC) hormones, which are released in response to ecological and social challenges, are increasingly employed to understand responses to anthropogenic disturbance. Here we investigate physiological and behavioural responses of female chacma baboons () to variation in spatial overlap and conflict with humans in their natural home range. The baboons resided in the Tokai Section of Table Mountain National Park in the Cape Peninsula of South Africa, where their home range included four types of habitats: protected, suburban, agricultural and mosaic areas. We studied the largest group of baboons in Tokai (70 individuals) and examined the effects of ranging in these different habitats on the faecal GCs and behaviour of all adult females in the troop ( = 16). We found time spent ranging in more anthropogenic habitats to be associated with higher levels of GCs, more aggression, less time socializing and shorter grooming bouts. Self-directed behaviour, however, varied and did not necessarily reflect physiological measures of stress. Taken together, the results of this study highlight the risks associated with ranging in anthropogenic environments and point to the need for a multifaceted approach to studying the negative impacts of human activities on animals so as to better inform conservation practices.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/conphys/coaa066DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7428446PMC
July 2020

Anthropogenic effects on the physiology and behaviour of chacma baboons in the Cape Peninsula of South Africa.

Conserv Physiol 2020 31;8(1):coaa066. Epub 2020 Jul 31.

Anthropology Program, Graduate Center, CUNY, New York, NY 10016, USA.

As animals increasingly occupy habitats in proximity to humans, with home ranges a mosaic of natural and anthropogenic landscapes, it becomes imperative from a conservation perspective to understand the impacts of human activities on wildlife. Many non-human primates share habitats with humans, an ability stemming largely from shared ecological needs due to our close evolutionary relationship. Such proximity, however, is often accompanied by direct conflict between humans and wildlife, leading to higher stress levels, injuries, mortality and behavioural changes, with detrimental effects on long-term health and fitness. Glucocorticoid (GC) hormones, which are released in response to ecological and social challenges, are increasingly employed to understand responses to anthropogenic disturbance. Here we investigate physiological and behavioural responses of female chacma baboons () to variation in spatial overlap and conflict with humans in their natural home range. The baboons resided in the Tokai Section of Table Mountain National Park in the Cape Peninsula of South Africa, where their home range included four types of habitats: protected, suburban, agricultural and mosaic areas. We studied the largest group of baboons in Tokai (70 individuals) and examined the effects of ranging in these different habitats on the faecal GCs and behaviour of all adult females in the troop ( = 16). We found time spent ranging in more anthropogenic habitats to be associated with higher levels of GCs, more aggression, less time socializing and shorter grooming bouts. Self-directed behaviour, however, varied and did not necessarily reflect physiological measures of stress. Taken together, the results of this study highlight the risks associated with ranging in anthropogenic environments and point to the need for a multifaceted approach to studying the negative impacts of human activities on animals so as to better inform conservation practices.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/conphys/coaa066DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7428446PMC
July 2020

Evaluation of Normothermic Machine Perfusion of Porcine Livers as a Novel Preclinical Model to Predict Biliary Clearance and Transporter-Mediated Drug-Drug Interactions Using Statins.

Drug Metab Dispos 2021 Sep 30;49(9):780-789. Epub 2021 Jul 30.

Department of Surgery, Leiden University Medical Centre (LUMC) Transplant Center, Leiden, The Netherlands (L.J.S., I.P.J.A.); The Netherlands Organization for Applied Scientific Research (TNO), Zeist, The Netherlands (L.J.S., J.M.D., W.H.J.V., E.v.d.S.); Quantitative Solutions (A.Z.X.Z.), Department of Drug Metabolism & Pharmacokinetic (P.P.C., S.K.C.), Takeda Pharmaceutical International, Cambridge, Massachusetts; Division of Systems Biomedicine and Pharmacology, Leiden Academic Centre for Drug Research (LACDR), Leiden, The Netherlands (C.A.J.K.); and Department of Clinical Pharmacy, St. Antonius Hospital, Nieuwegein and Utrecht, The Netherlands (C.A.J.K.)

There is a lack of translational preclinical models that can predict hepatic handling of drugs. In this study, we aimed to evaluate the applicability of normothermic machine perfusion (NMP) of porcine livers as a novel ex vivo model to predict hepatic clearance, biliary excretion, and plasma exposure of drugs. For this evaluation, we dosed atorvastatin, pitavastatin, and rosuvastatin as model drugs to porcine livers and studied the effect of common drug-drug interactions (DDIs) on these processes. After 120 minutes of perfusion, 0.104 mg atorvastatin ( = 3), 0.140 mg pitavastatin ( = 5), or 1.4 mg rosuvastatin ( = 4) was administered to the portal vein, which was followed 120 minutes later by a second bolus of the statin coadministered with OATP perpetrator drug rifampicin (67.7 mg). After the first dose, all statins were rapidly cleared from the circulation (hepatic extraction ratio > 0.7) and excreted into the bile. Presence of human-specific atorvastatin metabolites confirmed the metabolic capacity of porcine livers. The predicted biliary clearance of rosuvastatin was found to be closer to the observed biliary clearance. A rank order of the DDI between the various systems upon coadministration with rifampicin could be observed: atorvastatin (AUC ratio 7.2) > rosuvastatin (AUC ratio 3.1) > pitavastatin (AUC ratio 2.6), which is in good agreement with the clinical DDI data. The results from this study demonstrated the applicability of using NMP of porcine livers as a novel preclinical model to study OATP-mediated DDI and its effect on hepatic clearance, biliary excretion, and plasma profile of drugs. SIGNIFICANCE STATEMENT: This study evaluated the use of normothermic machine perfusion (NMP) of porcine livers as a novel preclinical model to study hepatic clearance, biliary excretion, plasma (metabolite) profile of statins, and OATP-mediated DDI. Results showed that NMP of porcine livers is a reliable model to study OATP-mediated DDI. Overall, the rank order of DDI severity indicated in these experiments is in good agreement with clinical data, indicating the potential importance of this new ex vivo model in early drug discovery.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1124/dmd.121.000521DOI Listing
September 2021

Omega-3 fatty acids are associated with blood-brain barrier integrity in a healthy aging population.

Brain Behav 2021 Aug 29;11(8):e2273. Epub 2021 Jul 29.

Department of Psychology, School of Behavioral Health, Loma Linda University, Loma Linda, California, USA.

In aging populations, omega-3 polyunsaturated fatty acids (PUFAs) have been associated with better cognitive function, slower rates of cognitive decline, and lower risk of developing dementia. Animal studies have shown that diets rich in omega-3 PUFAs reduce blood-brain barrier (BBB) disruption associated with aging, but this has yet to be observed in humans. Forty-five healthy subjects (mean age, 76 years) were recruited and underwent cognitive assessment (verbal learning and memory, language, processing speed, executive function, and motor control) and measurement of PUFAs. Forty of the same subjects also underwent magnetic resonance imaging (MRI) to measure BBB integrity (K using dynamic contrast-enhanced MRI). The long chain omega-3 score (DHA+EPA) was negatively correlated with K values in the internal capsule, indicating higher omega-3 levels were associated with greater BBB integrity in this region (r = -0.525, p = .004). Trends were observed for a positive correlation between the long chain omega-3 score and both memory and language scores, but not with executive function, speed, or motor control. The omega-6 score was not significantly correlated with any cognitive scores or K values. The significant correlations between long chain omega-3 levels and BBB integrity provide a possible mechanism by which omega-3 PUFAs are associated with brain health.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/brb3.2273DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8413753PMC
August 2021

Evaluating the impact of risk factors on in-hospital mortality for octogenarians undergoing cardiac surgery.

J Card Surg 2021 Oct 28;36(10):3996. Epub 2021 Jul 28.

Medical School, University of Liverpool, Liverpool, UK.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/jocs.15884DOI Listing
October 2021

Neutrophil Extracellular Traps in Colorectal Cancer Progression and Metastasis.

Int J Mol Sci 2021 Jul 6;22(14). Epub 2021 Jul 6.

Department of Clinical Sciences, Malmö, Section for Surgery, Lund University, 214 28 Malmö, Sweden.

Neutrophils form sticky web-like structures known as neutrophil extracellular traps (NETs) as part of innate immune response. NETs are decondensed extracellular chromatin filaments comprising nuclear and cytoplasmic proteins. NETs have been implicated in many gastrointestinal diseases including colorectal cancer (CRC). However, the regulatory mechanisms of NET formation and potential pharmacological inhibitors in the context of CRC have not been thoroughly discussed. In this review, we intend to highlight roles of NETs in CRC progression and metastasis as well as the potential of targeting NETs during colon cancer therapy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/ijms22147260DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8307027PMC
July 2021

Exocrine Pancreatic Insufficiency Following Gastric Resectional Surgery-is Routine Pancreatic Enzyme Replacement Therapy Necessary?

Indian J Surg Oncol 2021 Jun 5;12(2):391-396. Epub 2021 Apr 5.

Department of General Surgery and Upper GI Surgery, Christian Medical College Hospital, Vellore, 632004 India.

The data on exocrine pancreatic insufficiency (EPI) following gastric resectional surgery is variable, ranging from 26% to as high as 100%. This study aimed to document symptomatic EPI following gastric resectional surgery and to objectively document EPI, by fecal elastase (FE) testing. This was a cross-sectional study among patients undergoing gastric resection for adenocarcinoma of the stomach, at the Upper Gastrointestinal Surgical Unit at the Christian Medical College Hospital, Vellore, India. A detailed questionnaire was administered to the patients in the postoperative period, to evaluate clinical symptoms of EPI. Further, study participants were tested for FE pre- and postoperatively. Of the 60 patients in this study, the postoperative questionnaire administered to all patients during follow up. None showed symptoms suggestive of EPI. Pre- and post-operative FE testing were feasible in 27 of the 60 patients, which showed a 33% incidence of EPI. None of the patients had clinical symptoms of EPI, following gastric resectional surgery, on short-term follow-up. However, more than a third of the patients tested developed asymptomatic EPI after gastric resectional surgery, based on FE testing. This may be explained by the fact that in the early postoperative period, EPI following gastric resectional surgery perhaps has a mild, subclinical presentation. Therefore routine pancreatic supplementation after gastric resectional surgery may not be necessary. However, one needs to carefully look for worsening of symptoms of EPI on long-term follow-up, which may necessitate appropriate investigations followed by pancreatic enzyme replacement therapy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s13193-021-01315-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8272745PMC
June 2021

Cell-type-specific meQTLs extend melanoma GWAS annotation beyond eQTLs and inform melanocyte gene-regulatory mechanisms.

Am J Hum Genet 2021 09 21;108(9):1631-1646. Epub 2021 Jul 21.

Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD 20892, USA. Electronic address:

Although expression quantitative trait loci (eQTLs) have been powerful in identifying susceptibility genes from genome-wide association study (GWAS) findings, most trait-associated loci are not explained by eQTLs alone. Alternative QTLs, including DNA methylation QTLs (meQTLs), are emerging, but cell-type-specific meQTLs using cells of disease origin have been lacking. Here, we established an meQTL dataset by using primary melanocytes from 106 individuals and identified 1,497,502 significant cis-meQTLs. Multi-QTL colocalization with meQTLs, eQTLs, and mRNA splice-junction QTLs from the same individuals together with imputed methylome-wide and transcriptome-wide association studies identified candidate susceptibility genes at 63% of melanoma GWAS loci. Among the three molecular QTLs, meQTLs were the single largest contributor. To compare melanocyte meQTLs with those from malignant melanomas, we performed meQTL analysis on skin cutaneous melanomas from The Cancer Genome Atlas (n = 444). A substantial proportion of meQTL probes (45.9%) in primary melanocytes is preserved in melanomas, while a smaller fraction of eQTL genes is preserved (12.7%). Integration of melanocyte multi-QTLs and melanoma meQTLs identified candidate susceptibility genes at 72% of melanoma GWAS loci. Beyond GWAS annotation, meQTL-eQTL colocalization in melanocytes suggested that 841 unique genes potentially share a causal variant with a nearby methylation probe in melanocytes. Finally, melanocyte trans-meQTLs identified a hotspot for rs12203592, a cis-eQTL of a transcription factor, IRF4, with 131 candidate target CpGs. Motif enrichment and IRF4 ChIP-seq analysis demonstrated that these target CpGs are enriched in IRF4 binding sites, suggesting an IRF4-mediated regulatory network. Our study highlights the utility of cell-type-specific meQTLs.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ajhg.2021.06.018DOI Listing
September 2021

Development of antibacterial compounds that constrain evolutionary pathways to resistance.

Elife 2021 07 19;10. Epub 2021 Jul 19.

Department of Chemistry and Chemical Biology, Harvard University, Cambridge, United States.

Antibiotic resistance is a worldwide challenge. A potential approach to block resistance is to simultaneously inhibit WT and known escape variants of the target bacterial protein. Here, we applied an integrated computational and experimental approach to discover compounds that inhibit both WT and trimethoprim (TMP) resistant mutants of dihydrofolate reductase (DHFR). We identified a novel compound (CD15-3) that inhibits WT DHFR and its TMP resistant variants L28R, P21L and A26T with IC 50-75 µM against WT and TMP-resistant strains. Resistance to CD15-3 was dramatically delayed compared to TMP in in vitro evolution. Whole genome sequencing of CD15-3-resistant strains showed no mutations in the target folA locus. Rather, gene duplication of several efflux pumps gave rise to weak (about twofold increase in IC) resistance against CD15-3. Altogether, our results demonstrate the promise of strategy to develop evolution drugs - compounds which constrain evolutionary escape routes in pathogens.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.7554/eLife.64518DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8331180PMC
July 2021

Baseline characteristics of participants in the LANDMARC trial: A 3-year, -india, prospective, longitudinal study to assess management and real-world outcomes of diabetes mellitus.

Endocrinol Diabetes Metab 2021 Jul 8;4(3):e00231. Epub 2021 Feb 8.

Center for Diabetes & Endocrine Care Srinagar India.

Introduction: Longitudinal data on progression, complications, and management of type 2 diabetes mellitus (T2DM) across India are scarce. LANDMARC (CTRI/2017/05/008452), the first -India, longitudinal, prospective, observational study, aims to understand the management and real-world outcomes of T2DM over 3 years.

Methods: Adults (≥25 to ≤60 years old at T2DM diagnosis; diabetes duration ≥2 years at enrollment; controlled/uncontrolled on ≥2 anti-diabetic agents) were enrolled. Baseline characteristics were analyzed using descriptive statistics.

Results: Of the 6279 recruited participants, 6236 were eligible for baseline assessment (56.6% [/ = 3528/6236] men; mean ± SD age: 52.1 ± 9.2 years, diabetes duration: 8.6 ± 5.6 years). mean ± SD HbA1c, fasting plasma glucose, and postprandial glucose values were 64 ± 17 mmol/mol (8.1 ± 1.6%), 142.8 ± 50.4 mg/dl, and 205.7 ± 72.3 mg/dl, respectively. Only 25.1% (/ = 1122/6236) participants had controlled glycemia (HbA1c < 53 mmol/mol, <7%). Macrovascular and microvascular complications were prevalent in 2.3% (/ = 145/6236) and 14.5% (/ = 902/6236) participants, respectively. Among those with complications, non-fatal myocardial infarction (/ = 74/145, 51.0%) and neuropathy (/ = 737/902, 81.7%) were the most reported macrovascular and microvascular complication, respectively. Hypertension (/ = 2566/3281, 78.2%) and dyslipidemia (/ = 1635/3281, 49.8%) were the most reported cardiovascular risks. Majority (74.5%; / = 4643/6236) were taking oral anti-diabetic drugs (OADs) only, while 24.4% (/ = 1522/6236) participants were taking OADs+insulin. Biguanides (/ = 5796/6236, 92.9%) and sulfonylureas (/ = 4757/6236, 76.3%) were the most reported OADs. Basal (/ = 837/6236, 13.4%) and premix (/ = 684/6236, 11.0%) insulins were the most reported insulins.

Conclusions: Baseline data from LANDMARC help understand the clinical/medical profile of study participants and underscore the extent of suboptimal glycemic control and prevalence of associated complications in a vast majority of Indians with T2DM.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/edm2.231DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8279635PMC
July 2021

Incidence and Nature of Lower-Limb Deep Vein Thrombosis in Patients with Polytrauma on Thromboprophylaxis: A Prospective Cohort Study.

Vasc Health Risk Manag 2021 5;17:395-405. Epub 2021 Jul 5.

Department of Trauma, University Medical Center Utrecht, Utrecht, Netherlands.

Purpose: Deep vein thrombosis (DVT) is common among the severely injured and may lead to pulmonary embolism (PE), which can be life threatening. Thromboprophylaxis may reduce the incidence of venous thromboembolism (VTE); it does not guarantee complete protection. This study's primary aim was to determine the incidence and nature of lower-limb DVT in polytrauma patients taking prophylaxis. The secondary objective was to assess the incidence of DVT-related complications, including the development of PE and death.

Patients And Methods: This prospective observational study included patients age 18 years or older who presented with polytrauma directly from the scene and were admitted into the trauma unit between March 1, 2020 and August 31, 2020. All patients underwent lower-limb ultrasound during their hospital course to diagnose DVT.

Results: A total of 169 patients underwent extremity Doppler ultrasound to detect DVT. Of these, 69 patients (40.8%) were considered at the highest-risk for VTE development. For VTE prophylaxis, 115 patients (68%) received pharmacologic agents, and 54 patients (32%) had intermittent pneumatic compression on admission. Three patients (1.8%) developed DVT despite prophylaxis. Four patients (2.4%) developed PE during the index presentation and were diagnosed between days 3 and 13 after injury. Early DVT was not detected in any patients with diagnosed PE. Overall, nine patients (5.33%) died, but no in-hospital deaths were related to DVT and/or PE.

Conclusion: The incidence of DVT in polytrauma patients remains low in our small series, perhaps because of the mandatory VTE risk assessment for all hospitalized patients and the early initiation of prophylaxis. Using a trauma center registry to measure DVT and PE incidence regularly is recommended to improve trauma care quality.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2147/VHRM.S314951DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8275102PMC
August 2021

Difference in mortality among individuals admitted to hospital with COVID-19 during the first and second waves in South Africa: a cohort study.

Lancet Glob Health 2021 09 9;9(9):e1216-e1225. Epub 2021 Jul 9.

National Institute for Communicable Diseases of the National Health Laboratory Service, Johannesburg, South Africa; School of Public Health, Faculty of Health Sciences, University of Witwatersrand, Johannesburg, South Africa.

Background: The first wave of COVID-19 in South Africa peaked in July, 2020, and a larger second wave peaked in January, 2021, in which the SARS-CoV-2 501Y.V2 (Beta) lineage predominated. We aimed to compare in-hospital mortality and other patient characteristics between the first and second waves.

Methods: In this prospective cohort study, we analysed data from the DATCOV national active surveillance system for COVID-19 admissions to hospital from March 5, 2020, to March 27, 2021. The system contained data from all hospitals in South Africa that have admitted a patient with COVID-19. We used incidence risk for admission to hospital and determined cutoff dates to define five wave periods: pre-wave 1, wave 1, post-wave 1, wave 2, and post-wave 2. We compared the characteristics of patients with COVID-19 who were admitted to hospital in wave 1 and wave 2, and risk factors for in-hospital mortality accounting for wave period using random-effect multivariable logistic regression.

Findings: Peak rates of COVID-19 cases, admissions, and in-hospital deaths in the second wave exceeded rates in the first wave: COVID-19 cases, 240·4 cases per 100 000 people vs 136·0 cases per 100 000 people; admissions, 27·9 admissions per 100 000 people vs 16·1 admissions per 100 000 people; deaths, 8·3 deaths per 100 000 people vs 3·6 deaths per 100 000 people. The weekly average growth rate in hospital admissions was 20% in wave 1 and 43% in wave 2 (ratio of growth rate in wave 2 compared with wave 1 was 1·19, 95% CI 1·18-1·20). Compared with the first wave, individuals admitted to hospital in the second wave were more likely to be age 40-64 years (adjusted odds ratio [aOR] 1·22, 95% CI 1·14-1·31), and older than 65 years (aOR 1·38, 1·25-1·52), compared with younger than 40 years; of Mixed race (aOR 1·21, 1·06-1·38) compared with White race; and admitted in the public sector (aOR 1·65, 1·41-1·92); and less likely to be Black (aOR 0·53, 0·47-0·60) and Indian (aOR 0·77, 0·66-0·91), compared with White; and have a comorbid condition (aOR 0·60, 0·55-0·67). For multivariable analysis, after adjusting for weekly COVID-19 hospital admissions, there was a 31% increased risk of in-hospital mortality in the second wave (aOR 1·31, 95% CI 1·28-1·35). In-hospital case-fatality risk increased from 17·7% in weeks of low admission (<3500 admissions) to 26·9% in weeks of very high admission (>8000 admissions; aOR 1·24, 1·17-1·32).

Interpretation: In South Africa, the second wave was associated with higher incidence of COVID-19, more rapid increase in admissions to hospital, and increased in-hospital mortality. Although some of the increased mortality can be explained by admissions in the second wave being more likely in older individuals, in the public sector, and by the increased health system pressure, a residual increase in mortality of patients admitted to hospital could be related to the new Beta lineage.

Funding: DATCOV as a national surveillance system is funded by the National Institute for Communicable Diseases and the South African National Government.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/S2214-109X(21)00289-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8270522PMC
September 2021

Examining Experimental Raman Mode Behavior in Mono- and Bilayer 2H-TaSe via Density Functional Theory: Implications for Quantum Information Science.

ACS Appl Nano Mater 2021 ;4(2)

National Institute of Standards and Technology (NIST), Gaithersburg, Maryland 20899, United States.

Tantalum diselenide (TaSe) is a metallic transition metal dichalcogenide whose structure and vibrational behavior strongly depend on temperature and thickness, and this behavior includes the emergence of charge density wave (CDW) states at very low temperatures. In this work, observed Raman modes for mono- and bilayer are described across several spectral regions and compared to those seen in the bulk case. These modes, which include an experimentally observed forbidden Raman mode and low-frequency CDWs, are then matched to corresponding vibrations predicted by density functional theory (DFT). The reported match between experimental and computational results supports the presented vibrational visualizations of these modes. Support is also provided by experimental phonons observed in additional Raman spectra as a function of temperature and thickness. These results highlight the importance of understanding CDWs since they are likely to play a fundamental role in the future realization of solid-state quantum information platforms based on nonequilibrium phenomena.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/acsanm.0c03222DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8268966PMC
January 2021

Comprehensive Clinical and Molecular Characterization of -Mutant Colorectal Cancer.

JCO Precis Oncol 2021 6;5. Epub 2021 Apr 6.

Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX.

Purpose: p.G12C mutations occur in approximately 3% of metastatic colorectal cancers (mCRC). Recently, two allosteric inhibitors of p.G12C have demonstrated activity in early phase clinical trials. There are no robust studies examining the behavior of this newly targetable population.

Methods: We queried the MD Anderson Cancer Center data set for patients with colorectal cancer who harbored p.G12C mutations between January 2003 and September 2019. Patients were analyzed for clinical characteristics, overall survival (OS), and progression-free survival (PFS) and compared against nonG12C. Next, we analyzed several internal and external data sets to assess immune signatures, gene expression profiles, hypermethylation, co-occurring mutations, and proteomics.

Results: Among the 4,632 patients with comprehensive molecular profiling, 134 (2.9%) were found to have p.G12C mutations. An additional 53 patients with single gene sequencing were included in clinical data but excluded from prevalence analysis allowing for 187 total patients. Sixty-five patients had de novo metastatic disease and received a median of two lines of chemotherapy without surgical intervention. For the first three lines of chemotherapy, the median PFS was 6.4 months (n = 65; 95% CI, 5.0 to 7.4 months), 3.9 months (n = 47; 95% CI, 2.9 to 5.9 months), and 3.0 months (n = 21; 95% CI, 2.0 to 3.4 months), respectively. p.G12C demonstrated higher rates of basal EGFR activation compared with nonG12C. When compared with an internal cohort of nonG12C, p.G12C patients had worse OS.

Conclusion: PFS is poor for patients with p.G12C metastatic colorectal cancer. OS was worse in p.G12C compared with nonG12C patients. Our data highlight the innate resistance to chemotherapy for p.G12C patients and serve as a historical comparator for future clinical trials.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1200/PO.20.00256DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8232253PMC
April 2021

Non-adiabatic ring polymer molecular dynamics with spin mapping variables.

J Chem Phys 2021 May;154(18):184106

Department of Chemistry, University of Rochester, 120 Trustee Road, Rochester, New York 14627, USA.

We present a new non-adiabatic ring polymer molecular dynamics (NRPMD) method based on the spin mapping formalism, which we refer to as the spin mapping NRPMD (SM-NRPMD) approach. We derive the path-integral partition function expression using the spin coherent state basis for the electronic states and the ring polymer formalism for the nuclear degrees of freedom. This partition function provides an efficient sampling of the quantum statistics. Using the basic properties of the Stratonovich-Weyl transformation, we further justify a Hamiltonian that we propose for the dynamical propagation of the coupled spin mapping variables and the nuclear ring polymer. The accuracy of the SM-NRPMD method is numerically demonstrated by computing the nuclear position and population auto-correlation functions of non-adiabatic model systems. The results obtained using the SM-NRPMD method agree very well with the numerically exact results. The main advantage of using the spin mapping variables over the harmonic oscillator mapping variables is numerically demonstrated, where the former provides nearly time-independent expectation values of physical observables for systems under thermal equilibrium. We also explicitly demonstrate that SM-NRPMD provides invariant dynamics upon various ways of partitioning the state-dependent and state-independent potentials.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1063/5.0051456DOI Listing
May 2021

Indian Expert Review on Use of Teneligliptin in patients with Diabetes and its Safety and Efficacy (INTENSE).

J Assoc Physicians India 2021 Jan;69(1):61-70

Senior Consultant, Apollo Hospitals, Bhubaneswar, Orissa.

Introduction: Management of diabetes in India remains less than satisfactory despite a huge prevalence of type 2 diabetes (T2D). Associated obesity, inadequate lifestyle modifications and burden of treatment costs are certain major issues contributing to inadequate management of diabetes in India.

Aim: To evaluate the use of Teneligliptin in patients with diabetes and its safety, efficacy and cost effectiveness especially in Indian patients with T2D.

Methods: A detailed analysis of the best available scientific evidence (clinical trials, meta-analyses and real-world experience) was performed to create an evidence driven understanding of teneligliptin's efficacy, safety and cost effectiveness. Fourteen leading endocrinologists contributed as experts and the modified Delphi process was followed. Evidences and clinical questions were discussed over a series of web and in a live meeting. Final draft was created based on the opinions endorsed by the experts.

Results: Teneligliptin is the most commonly used gliptin in India and exhibits pharmacokinetic and pharmacodynamic advantages as well as greater cost effectiveness compared to other gliptins. It has been recognized as an efficacious and well tolerated antidiabetic agent both as monotherapy and in combination based on multiple clinical trials, meta-analyses and real world studies. Teneligliptin as add on therapy to other antidiabetic drugs (OADs) or insulin has provided significant reductions in HbA1c, fasting plasma glucose (FPG) and postprandial plasma glucose (PPG) levels and is generally well tolerated with low risk of hypoglycemia both in short term and long term. Studies have also proven its efficacy in ameliorating glucose fluctuations, reducing post prandial insulin requirement, increasing active incretin levels and improving pancreatic β cells function. Efficacy and safety has also been proven in all age groups, all stages of renal disease and mild to moderate hepatic disease. QT prolongation is not seen even with maximum recommended dose of 40 mg/day.

Conclusion: Teneligliptin has firmly positioned itself as a very important drug in the armamentarium for managing T2D. It offers efficacy, safety and cost-effective therapeutic choice in Indian patients with T2D.
View Article and Find Full Text PDF

Download full-text PDF

Source
January 2021

Assessing lodging damage of jute crop due to super cyclone Amphan using multi-temporal Sentinel-1 and Sentinel-2 data over parts of West Bengal, India.

Environ Monit Assess 2021 Jul 4;193(8):464. Epub 2021 Jul 4.

Agro-Ecosystem and Modeling Division, Agricultural Sciences and Applications Group, National Remote Sensing Centre, Indian Space Research Organization, Hyderabad, India.

The present study is a maiden attempt to assess jute crop lodging due to super cyclone Amphan (20 May 2020) by synergistic use of Sentinel-2 (optical) and Sentinel-1 (SAR) data over part of West Bengal, India. Pre-event Sentinel-2 data (9 April, 14 May) along with the ground information were used to map the jute crop of the affected districts with accuracy of 85%. The cross-polarized backscatter (σ) of Sentinel-1 was found to be sensitive to the sudden change in the canopy structure due to lodging and partial flooding. [Formula: see text](σ - σ) indicating post-event damage was > 2.5 dB over the affected jute crop and [Formula: see text] (σ - σ) representing post-event recovery showed > 1.5 dB for recovered crop, depending on the crop vigor/height. Decision matrix was prepared combining [Formula: see text] and [Formula: see text] for NDVI-based crop vigor strata (low, medium, and high) to classify the area into affected, marginally affected and normal. Overall accuracy of the classified map was found to be 84.12% with kappa coefficient of 0.74. Nearly, 12.5% of the jute area, i.e., 38,119 ha was found to be either affected or marginally affected due to Amphan and distributed in the southern part of Murshidabad, north-eastern Nadia, northern 24 Paraganas (N), and middle region of Hooghli district. Geospatial map of block-wise affected jute area was prepared to facilitate informed decision making. The study demonstrated an operational methodology for assessing crop lodging due to natural calamities to support relief management and crop insurance.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s10661-021-09220-wDOI Listing
July 2021

Pulmonary artery sarcoma or chronic pulmonary thromboembolism - A diagnostic dilemma and an anaesthetic challenge.

Indian J Anaesth 2021 May 20;65(5):410-411. Epub 2021 May 20.

Department of Cardiothoracic and Vascular Surgery, Rabindranath Tagore International Institute of Cardiac Sciences, Kolkata, West Bengal, India.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.4103/ija.IJA_1235_20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8202793PMC
May 2021

Prevalence and Risk Factors of Infection with High Risk Human Papilloma Viruses among HIV-Positive Women with Clinical Manifestations of Tuberculosis in a Middle-Income Country.

Biomedicines 2021 Jun 16;9(6). Epub 2021 Jun 16.

Department of Medicine, University of California San Francisco, San Francisco, CA 94143, USA.

Women living with HIV-1 are at high risk of infection with human papillomavirus of high carcinogenic risk (HR HPVs). (TB) promotes HPV infection and increases the risk to develop HPV-associated cancer. Our knowledge of persisting HR HPVs genotypes, and of the factors promoting HR HPV infection in people living with HIV-1 with clinical TB manifestations is sparse. Here, we analyzed 58 women living with HIV-1 with clinical TB manifestations (WLWH with TB) followed up in specialized centers in Russia, a middle income country endemic for HIV-1 and TB, for the presence in cervical smears of DNA of twelve HR HPV genotypes. DNA encoding HPV16 E5, E6/E7 was sequenced. Sociodemographic data of patients was collected by questionnaire. All women were at C2-C3 stages of HIV-infection (by CDC). The majority were over 30 years old, had secondary education, were unemployed, had sexual partners, experienced 2-3 pregnancies and at least one abortion, and were smokers. The most prevalent was HPV16 detected in the cervical smears of 38% of study participants. Altogether 34.5% of study participants were positive for HR HPV types other than HPV16; however, but none of these types was seen in more than 7% of tested samples. Altogether, 20.7% of study participants were positive for several HR HPV types. Infections with HPVs other than HPV16 were common among WLWH with generalized TB receiving combined ART/TB-therapy, and associated with their ability to work, indirectly reflecting both their health and lifestyle. The overall prevalence of HR HPVs was associated with sexual activity of women reflected by the number of pregnancies, and of HPV 16, with young age; none was associated to CD4+-counts, route of HIV-infection, duration of life with HIV, forms of TB-infection, or duration of ART, characterizing the immune status. Thus, WLWH with TB-especially young-were predisposed to infection with HPV16, advancing it as a basis for a therapeutic HPV vaccine. Phylogenetic analysis of HPV16 E5, E6/E7 DNA revealed no common ancestry; sequences were similar to those of the European and American HPV16 strains, indicating that HPV vaccine for WLWH could be the same as HPV16 vaccines developed for the general population. Sociodemographic and health correlates of HR HPV prevalence in WLWH deserve further analysis to develop criteria/recommendations for prophylactic catch-up and therapeutic HPV vaccination of this highly susceptible and vulnerable population group.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/biomedicines9060683DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8234035PMC
June 2021

A MEMS Ultra-Wideband (UWB) Power Sensor with a Fe-Co-B Core Planar Inductor and a Vibrating Diaphragm Capacitor.

Sensors (Basel) 2021 Jun 3;21(11). Epub 2021 Jun 3.

Electrical and Computer Engineering Department, University of Windsor, Windsor, ON N9B 3P4, Canada.

The design of a microelectromechanical systems (MEMS) ultra-wideband (UWB) RMS power sensor is presented. The sensor incorporates a microfabricated Fe-Co-B core planar inductor and a microfabricated vibrating diaphragm variable capacitor on adhesively bonded glass wafers in a footprint area of 970 × 970 µm to operate in the 3.1-10.6 GHz UWB frequency range. When exposed to a far-field UWB electromagnetic radiation, the planar inductor acts as a loop antenna to generate a frequency-independent voltage across the MEMS capacitor. The voltage generates a coulombic attraction force between the diaphragm and backplate that deforms the diaphragm to change the capacitance. The frequency-independent capacitance change is sensed using a transimpedance amplifier to generate an output voltage. The sensor exhibits a linear capacitance change induced voltage relation and a calculated sensitivity of 4.5 aF/0.8 µA/m. The sensor can be used as a standalone UWB power sensor or as a 2D array for microwave-based biomedical diagnostic imaging applications or for non-contact material characterization. The device can easily be tailored for power sensing in other application areas such as, 5G, WiFi, and Internet-of-Things (IoT). The foreseen fabrication technique can rely on standard readily available microfabrication techniques.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/s21113858DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8199788PMC
June 2021

cAMP binding to closed pacemaker ion channels is non-cooperative.

Nature 2021 Jul 30;595(7868):606-610. Epub 2021 Jun 30.

Department of Neuroscience, University of Wisconsin-Madison, Madison, WI, USA.

Electrical activity in the brain and heart depends on rhythmic generation of action potentials by pacemaker ion channels (HCN) whose activity is regulated by cAMP binding. Previous work has uncovered evidence for both positive and negative cooperativity in cAMP binding, but such bulk measurements suffer from limited parameter resolution. Efforts to eliminate this ambiguity using single-molecule techniques have been hampered by the inability to directly monitor binding of individual ligand molecules to membrane receptors at physiological concentrations. Here we overcome these challenges using nanophotonic zero-mode waveguides to directly resolve binding dynamics of individual ligands to multimeric HCN1 and HCN2 ion channels. We show that cAMP binds independently to all four subunits when the pore is closed, despite a subsequent conformational isomerization to a flip state at each site. The different dynamics in binding and isomerization are likely to underlie physiologically distinct responses of each isoform to cAMP and provide direct validation of the ligand-induced flip-state model. This approach for observing stepwise binding in multimeric proteins at physiologically relevant concentrations can directly probe binding allostery at single-molecule resolution in other intact membrane proteins and receptors.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41586-021-03686-xDOI Listing
July 2021

Electronic and thermal transport in novel carbon-based bilayer with tetragonal rings: a combined study using first-principles and machine learning approach.

Phys Chem Chem Phys 2021 Jul;23(27):14608-14616

Department of Physics, University of Calcutta, 92, A.P.C. Road, Kolkata 700 009, India.

In this article, the structural, electronic and thermal transport characteristics of bilayer tetragonal graphene (TG) are systematically explored with a combination of first-principles calculations and machine-learning interatomic potential approaches. Optimized ground state geometry of the bilayer TG structure is predicted and examined by employing various stability criteria. Electronic bandstructure analysis confirmed that bilayer TG exhibits a metallic band structure similar to the monolayer T-graphene structure. Thermal transport characteristics of the bilayer TG structure are explored by analysing thermal conductivity, the Seebeck coefficient, and electrical conductivity. The electronic part of the thermal conductivity shows linearly increasing behaviour with temperature, however the lattice part exhibits the opposite character. The lattice thermal conductivity part is investigated in terms of the three phonon scattering rates and weighted phase space. On the other hand, the Seebeck coefficient goes through a transition from negative to positive values with increasing temperature. The Wiedemann-Franz law regarding electrical transport of the bilayer TG is verified and confirms the universal Lorentz number. Specific heat of the bilayer TG structure follows the Debye model at low temperature and constant behaviour at high temperature. Moreover, the Debye temperature of the bilayer TG structure is verified by ab initio calculations as well as fitting the specific heat data using the Debye model.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1039/d1cp01423dDOI Listing
July 2021

A study of serum growth differentiation factor 15 in Indian women with and without gestational diabetes mellitus in the third trimester of pregnancy and its association with pro-inflammatory markers and glucose metabolism.

Diabetol Int 2021 Jul 21;12(3):254-259. Epub 2020 Nov 21.

Department of Endocrinology and Metabolism, IPGME&R and SSKM Hospital, 244 AJC Bose road, Kolkata, West Bengal India.

The pathogenesis of gestational diabetes mellitus (GDM) is multifactorial and it shares many features with type 2 diabetes mellitus. Growth differentiation factor 15 (GDF-15), a member of transforming growth factor-β superfamily, is expressed in a high amount in the placenta in addition to other organs. This cross-sectional study was performed to assess the difference of GDF-15 and pro-inflammatory cytokines between pregnant women with or without GDM, and to explore the possible association of GDF-15 with the parameters of dysglycemia (Serum insulin, HOMA-IR, fasting, 60 min, and 120 min post-75 gm oral glucose plasma glucose levels) and inflammation (IL-6 and TNF-α) in women with GDM at 24-28 weeks of gestation. Thirty-five women with GDM and 30 age-matched non-diabetic pregnant control (NDPC) subjects were recruited for the study. Mean serum GDF-15, IL-6, and TNF-α levels were significantly higher in GDM in comparison to the NDPC population. These differences persisted even after adjusting for the possible confounders like maternal age and BMI. GDF-15 level showed a positive correlation with parameters of dysglycemia (Serum insulin, HOMA-IR, fasting, 60 min, and 120 min post-75 gm oral glucose plasma glucose levels) but a variable correlation with the markers of inflammation. In conclusion, our study provides evidence that, in Indian women, serum GDF-15 level is higher in GDM in comparison to age-matched pregnant subjects without GDM in the early third trimester pregnancy. Moreover, in third trimester, GDF-15 level increases with increase in plasma glucose and insulin resistance.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s13340-020-00478-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8172661PMC
July 2021

Seasonal spatial dynamics of butterfly migration.

Ecol Lett 2021 Sep 18;24(9):1814-1823. Epub 2021 Jun 18.

School of Biological Sciences, The University of Queensland, Saint Lucia, Qld, Australia.

Understanding the seasonal movements of migratory species underpins ecological studies. Several hundred butterfly species show migratory behaviour, yet the spatial pattern of these migrations is poorly understood. We developed climatic niche models for 405 migratory butterfly species globally to estimate patterns of seasonal movement and the distribution of seasonal habitat suitability. We found strong seasonal variation in habitat suitability for most migratory butterflies with >75% of pixels within their distributions showing seasonal switching in predicted occupancy for 85% of species. The greatest rate of seasonal switching occurred in the tropics. Several species showed extreme range fluctuations between seasons, exceeding 10-fold for 53 species (13%) and more than 100-fold for nine species (2%), suggesting that such species may be at elevated extinction risk. Our results can be used to search for the ecological processes that underpin migration in insects, as well as to design conservation interventions for declining migratory insects.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/ele.13787DOI Listing
September 2021

Quantification of Human Epidermal Growth Factor Receptor 2 by Immunopeptide Enrichment and Targeted Mass Spectrometry in Formalin-Fixed Paraffin-Embedded and Frozen Breast Cancer Tissues.

Clin Chem 2021 Jul;67(7):1008-1018

Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.

Background: Conventional HER2-targeting therapies improve outcomes for patients with HER2-positive breast cancer (BC), defined as tumors showing HER2 protein overexpression by immunohistochemistry and/or ERBB2 gene amplification determined by in situ hybridization (ISH). Emerging HER2-targeting compounds show benefit in some patients with neither HER2 protein overexpression nor ERBB2 gene amplification, creating a need for new assays to select HER2-low tumors for treatment with these compounds. We evaluated the analytical performance of a targeted mass spectrometry-based assay for quantifying HER2 protein in formalin-fixed paraffin-embedded (FFPE) and frozen BC biopsies.

Methods: We used immunoaffinity-enrichment coupled to multiple reaction monitoring-mass spectrometry (immuno-MRM-MS) to quantify HER2 protein (as peptide GLQSLPTHDPSPLQR) in 96 frozen and 119 FFPE BC biopsies. We characterized linearity, lower limit of quantification (LLOQ), and intra- and inter-day variation of the assay in frozen and FFPE tissue matrices. We determined concordance between HER2 immuno-MRM-MS and predicate immunohistochemistry and ISH assays and examined the benefit of multiplexing the assay to include proteins expressed in tumor subcompartments (e.g., stroma, adipose, lymphocytes, epithelium) to account for tissue heterogeneity.

Results: HER2 immuno-MRM-MS assay linearity was ≥103, assay coefficient of variation was 7.8% (FFPE) and 5.9% (frozen) for spiked-in analyte, and 7.7% (FFPE) and 7.9% (frozen) for endogenous measurements. Immuno-MRM-MS-based HER2 measurements strongly correlated with predicate assay HER2 determinations, and concordance was improved by normalizing to glyceraldehyde-3-phosphate dehydrogenase. HER2 was quantified above the LLOQ in all tumors.

Conclusions: Immuno-MRM-MS can be used to quantify HER2 in FFPE and frozen BC biopsies, even at low HER2 expression levels.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/clinchem/hvab047DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8260184PMC
July 2021
-->