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Insomnia is a highly prevalent disorder that is seen across all age groups causing significant morbidity to the patients. Its prevalence has further risen during COVID-19 pandemic. It is widely acknowledged that untreated insomnia can lead to significant health risks and socio-occupational dysfunction.A narrative review was conducted following focused search of databases.Available guidelines mention two different approaches for the management of insomnia-pharmacological and non-pharmacological. Non-pharmacological therapies like multicomponent cognitive behavior therapy for insomnia (CBT-I) have been advocated for the management of acute as well as chronic insomnia in the literature as it has been found efficacious and useful. Multiple variants of CBT-I, e.g., digitally delivered CBT-I, brief CBT-I have been tested during pandemic owing to closure of clinics. However, there are certain issues to be considered while choosing CBT-I as therapy. For example, like other forms of psychotherapies, is there a need for assessing the candidature of patient before administering CBT-I; is CBT-I free of adverse effects as commonly thought; is CBT-I more efficacious than hypnotics; and at last, how to manage cases that are not candidate for CBT-I.This narrative review addresses the scientific robustness of evidence for issues related to adherence, efficacy and adverse effects of non-pharmacological therapies. Available literature suggests that data related to adherence and efficacy of CBT-I suffer from methodological shortcomings and careful selection of patient is important for the successful therapy. At the same time, attempts have been made to shed light to the areas where CBT-I can be helpful in the management of insomnia.

Objective: Awake proning is an intervention that is being advocated for COVID-19 patients and has been suggested to improve the oxygenation, thereby decreasing oxygen requirements. We performed this systematic review with the aim of appraising the latest published evidence on the clinical effectiveness of awake proning in COVID-19 patients. Data sources: PubMed, EMBASE, The Cochrane Central Register of Controlled Trials (CENTRAL), Web of Science, Google Scholar, and one trial registry were searched until September 23, 2020, for studies on the use of awake proning for nonintubated COVID-19 patients. Study selection: Published or in-press peer-reviewed randomized control trials, case-control trials, and prospective or retrospective cohort studies in English language only were sought, assessing the effectiveness of awake proning for nonintubated patients diagnosed with COVID-19. Data results: We included 21 published studies (19 single arm and 2 with comparison group). Twenty-three registered clinical trials were identified. No randomized clinical trial has been published so far. Conclusions: Awake proning is probably safe and effective in enhancing oxygenation in nonintubated COVID-19 patients; however, there is insufficient evidence. Further high-quality clinical trials are urgently needed to assess the effectiveness of awake proning on a variety of patient-centered outcomes. How to cite this article: Parashar S, Karthik AR, Gupta R, Malviya D. Awake Proning for Nonintubated Adult Hypoxic Patients with COVID-19: A Systematic Review of the Published Evidence. Indian J Crit Care Med 2021;25(8):906–916.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections were rising during early summer 2021 in many countries as a result of the Delta variant. We assessed reverse transcription polymerase chain reaction swab positivity in the Real-time Assessment of Community Transmission–1 (REACT-1) study in England. During June and July 2021, we observed sustained exponential growth with an average doubling time of 25 days, driven by complete replacement of the Alpha variant by Delta and by high prevalence at younger, less-vaccinated ages. Prevalence among unvaccinated people [1.21% (95% credible interval 1.03%, 1.41%)] was three times that among double-vaccinated people [0.40% (95% credible interval 0.34%, 0.48%)]. However, after adjusting for age and other variables, vaccine effectiveness for double-vaccinated people was estimated at between ~50% and ~60% during this period in England. Increased social mixing in the presence of Delta had the potential to generate sustained growth in infections, even at high levels of vaccination.

Neuroendocrine tumors (NETs) are rare entities. Most common among them are gastroenteropancreatic neuroendocrine tumors (GEP-NETs) and pulmonary NETs. Most of them are indolent in nature. Colonic NETs are rare among GEP-NETs and mostly present with large size and with metastasis. Emergency presentation with hematochezia is rare in colonic NETs. This case report discusses a rare emergency presentation of colonic NETs and highlights their poor biological nature.

Wound irrigation is described as the flow of a solution through an exposed fracture surface to reduce the microbial colonization, to remove apparent foreign particles and wound exudates. . While recent literature and various in-vitro and in-vivo trials have cleared some clouds of doubt from the mind, it still remains a topic of debate. Normal saline remains the standard irrigation solution as it is non tissue toxic and has the same tonicity as body fluids. The quantity and duration of washing though is not standardized and is the surgeon's choice. This adds to the dilemma in the minds of the surgeon, with the timing of the debridement and the duration of wound irrigation depending on the surgeon's discretion. Future studies should aim to regulate the duration of the wound irrigation besides guiding about the ideal fluid volume to be used for the irrigation. Further, secondary end-points like the duration of hospital stay, rate of infections and use of hospital resources, should be computed to know about the adequacy of the wound debridement and irrigation. Antimicrobial solutions can kill microorganisms in the wound but are toxic to the host tissues as well, which limits their use. In addition, pulsatile (high pressure) lavage has not been seen to increase overall effectiveness. Recent research trials have found cumulative use of innovative solutions like phenols and EDTA along with enzymes to be encouraging though large randomized controlled trials are lacking.

Major depressive disorder (MDD) is often linked with a number of coexisting disorders with a relation that is poorly understood. The aim of this study was to find out the role of obstructive sleep apnea (OSA) in metabolic syndrome (MS) in subjects with MDD and to develop a model for factors leading to MS.It was a cross-sectional study conducted on 119 subjects. They were evaluated on sociodemographic and clinical parameters, Berlin questionnaire, and Quick Inventory of Depressive Symptomatology. Comparisons were made using appropriate statistics. Binary logistic regression was used to find out the role of clinical parameters in the development of MS.A total of 34% with MDD had a high risk of developing OSA while 19% had metabolic syndrome. Among all clinical variables, antidepressant exposure in terms of total fluoxetine units, duration of treatment, and risk of developing OSA was found to be significantly more in patients with MS. A higher risk of OSA was found to have a higher likelihood to cause MS in patients with MDD.There is a high risk of MS and OSA in subjects with MDD. The increased risk of MS is contributed by an increased risk of developing OSA among patients with MDD. Cross-sectional design and limited generalizability are the major limitations of this study.

Rapid COVID-19 diagnosis in the hospital is essential, although this is complicated by 30%–50% of nose/throat swabs being negative by SARS-CoV-2 nucleic acid amplification testing (NAAT). Furthermore, the D614G spike mutant dominates the pandemic and it is unclear how serological tests designed to detect anti-spike antibodies perform against this variant. We assess the diagnostic accuracy of combined rapid antibody point of care (POC) and nucleic acid assays for suspected COVID-19 disease due to either wild-type or the D614G spike mutant SARS-CoV-2. The overall detection rate for COVID-19 is 79.2% (95% CI 57.8–92.9) by rapid NAAT alone. The combined point of care antibody test and rapid NAAT is not affected by D614G and results in very high sensitivity for COVID-19 diagnosis with very high specificity., Graphical Abstract, Highlights Combined rapid antibody + nucleic acid detection correctly diagnoses SARS-CoV-2 Rapid antibody tests detect immune responses against SARS-CoV-2 bearing D614G Rapid SARS-CoV-2 antibody tests do not cross-react with antibodies to seasonal CoV False positivity in SARS-CoV-2 finger prick blood antibody tests can be very low, Mlcochova et al. report that combined rapid nucleic acid amplification testing (NAAT) and finger prick blood antibody tests can substantially improve the diagnosis of COVID-19 as compared to NAAT alone and is able to detect the SARS-CoV-2 Spike D614G variant that dominates the pandemic.

The present study provides an integrated method for utilizing the wastewaters from second generation (2G) ethanol pretreatment plant for microalgal biomass and lipid production. The study was conducted using a mixture of wastewaters (referred as MW; pH 4.3) generated after washing of acidic and alkaline-soaked lignocellulosic biomass prior to pretreatment process. The growth studies indicated that the thermotolerant strain of Chlorella pyrenoidosa (C. pyrenoidosa) M18 exhibited higher cell proliferation in wastewater as compared to freshwater. About 20–25% enhancement in biomass (509 mg L(−1) d(−1) ± 3.09) and lipid productivity (146 mg L(−1) d(−1) ± 1.34) was observed in MW. The total chlorophyll content and variable fluorescence by maximum fluorescence (Fv/Fm) ratio of strain cultivated in MW were 10.32 µg mL(−1) and 0.75, respectively. The use of MW also enhanced the content of saturated and monounsaturated fatty acids in total lipid. The exhausted wastewater medium obtained after harvesting the auto-flocculated biomass was also reused up to three successive growth cycles. The recycled medium without any nutrient addition could be used for two subsequent rounds with enhanced biomass (520 mg L(−1) d(−1) ± 4.07) and lipid (157.71 mg L(−1) d(−1) ± 1.09) productivities. This synergistic approach of cultivating thermotolerant microalgae with wastewater from 2G pretreatment plant provides an economical setup for development of commercial algal biofuel technology.

There has been enormous growth in the energy sector in the new millennium, and it has enhanced energy demand, creating an exponential rise in the capital investment in the energy industry in the last few years. Regular monitoring of the health of industrial equipment is necessary, and thus, the concept of structural health monitoring (SHM) comes into play. In this paper, the purpose is to highlight the importance of SHM systems and various techniques primarily used in pipelining industries. There have been several advancements in SHM systems over the years such as Point OFS (optical fiber sensor) for Corrosion, Distributed OFS for physical and chemical sensing, etc. However, these advanced SHM technologies are at their nascent stages of development, and thus, there are several challenges that exist in the industries. The techniques based on acoustic, UAVs (Unmanned Aerial Vehicles), etc. bring in various challenges, as it becomes daunting to monitor the deformations from both sides by employing only one technique. In order to determine the damages well in advance, it is necessary that the sensor is positioned inside the pipes and gives the operators enough time to carry out the troubleshooting. However, the mentioned technologies have been unable to indicate the errors, and thus, there is the requirement for a newer technology to be developed. The purpose of this review manuscript is to enlighten the readers about the importance of structural health monitoring in pipeline and wind turbine industries.

Incessant downscaling of advance CMOS devices have led device engineers to consider their placement of SiO2 and SiON layers with high-k gate dielectrics like HFO2, TiO2, and HfSiO(N). Intensive research has been carried out so far to develop these oxides into high-quality electronic materials. As per the specifications required by International Technology Roadmap for semiconductors, these gate oxides have felicitated in drastically reducing the leakage current. However, major problem remains unsolved before the possible use of high-k gate dielectric-based devices. The purpose of this chapter is to provide an in-depth analysis of the challenges in conventional CMOS technology and various issues pertaining to high-k gate dielectrics-based devices. It covers several technical and scientific challenges like choice of oxides, oxide deposition, their metallurgical and structural behavior, interface structure, charge trapping, flat band voltage, carrier mobility degradation, electronic defects, threshold voltage control, and gate dielectric wear and breakdown to achieve the oxide thickness as thin as possible. The combination of metal gates with high-k gate dielectrics seems to be a promising viable solution for further downscaling of CMOS-based devices. Besides this, high-k gate dielectrics-based devices like Tunnel FET are also discussed at length.

BackgroundThe US Food and Drug Administration (FDA) plays a critical role in bolstering public confidence in vaccines and the vaccine review process. An important tool for enhancing transparency and public trust is the FDA’s Vaccine and Biological Related Products Advisory Committee (VRBPAC), a group of external experts that advises on scientific issues related to the licensure of vaccines.ObjectiveTo analyze key features of VRBPAC meetings convened over 20 years; estimate the probability of advisory committee review of newly approved vaccines, focusing on vaccines targeting emerging diseases; and examine the speed of and variance in approval times as a function of VRBPAC review.MethodsCross-sectional study of VRBPAC meetings convened and new vaccine licensure applications approved between January 1, 2000, and December 31, 2019. We analyzed the frequency of VRBPAC meetings and sessions; the percentage of newly licensed vaccines reviewed by VRBPAC; and the number of days between the submission of the licensure application and the date of FDA approval.ResultsBetween 2000 and 2019, VRBPAC convened for a mean of 4.1 sessions per year. One-quarter of sessions was devoted to the review of specific vaccine products. During the same period, 44 new vaccine licensures were approved, 20% of which were for vaccines targeting emerging diseases. Almost half (48%) of successful new vaccine applications were reviewed by VRBPAC (n=21), a rate lower than for therapeutic applications. Among new applications targeting emerging diseases, 29% of non-influenza vaccines were reviewed by VRBPAC. There was no difference in the median time to approval as a function of VRBPAC review (364 days with VRBAC review vs. 365 days with no review, p=0.870).ConclusionThe FDA has convened VRBPAC for reviews of about half of its vaccine products, less frequently for vaccines against non-influenza emerging diseases. There is considerable scope for the FDA to increase VRBPAC engagement in the vaccine review process.

Ginsenosides, a group of tetracyclic saponins, accounts for the nutraceutical and pharmaceutical relevance of the ginseng (Panax sp.) herb. Owing to the associated therapeutic potential of ginsenosides, their demand has been increased significantly in the last two decades. However, a slow growth cycle, low seed production, and long generation time of ginseng have created a gap between the demand and supply of ginsenosides. The biosynthesis of ginsenosides involves an intricate network of pathways with multiple oxidation and glycosylation reactions. However, the exact functions of some of the associated genes/proteins are still not completely deciphered. Moreover, ginsenoside estimation and extraction using analytical techniques are not feasible with high efficiency. The present review is a step forward in recapitulating the comprehensive aspects of ginsenosides including their distribution, structural diversity, biotransformation, and functional attributes in both plants and animals including humans. Moreover, ginsenoside biosynthesis in the potential plant sources and their metabolism in the human body along with major regulators and stimulators affecting ginsenoside biosynthesis have also been discussed. Furthermore, this review consolidates biotechnological interventions to enhance the biosynthesis of ginsenosides in their potential sources and advancements in the development of synthetic biosystems for efficient ginsenoside biosynthesis to meet their rising industrial demands.

Korean ginseng is one of the most valuable medicinal plants worldwide. However, our understanding of ginseng proteomics is largely limited due to difficulties in the extraction and resolution of ginseng proteins because of the presence of natural contaminants such as polysaccharides, phenols, and glycosides. Here, we compared four different protein extraction methods, namely, TCA/acetone, TCA/acetone–MeOH/chloroform, phenol–TCA/acetone, and phenol–MeOH/chloroform methods. The TCA/acetone–MeOH/chloroform method displayed the highest extraction efficiency, and thus it was used for the comparative proteome profiling of leaf, root, shoot, and fruit by a label-free quantitative proteomics approach. This approach led to the identification of 2604 significantly modulated proteins among four tissues. We could pinpoint differential pathways and proteins associated with ginsenoside biosynthesis, including the methylerythritol 4–phosphate (MEP) pathway, the mevalonate (MVA) pathway, UDP-glycosyltransferases (UGTs), and oxidoreductases (CYP450s). The current study reports an efficient and reproducible method for the isolation of proteins from a wide range of ginseng tissues and provides a detailed organ-based proteome map and a more comprehensive view of enzymatic alterations in ginsenoside biosynthesis.

Sleep disorders often disturb sleep. Daytime symptoms of disturb sleep mimic that of depression, somatoform disorder, fibromyalgia and chronic fatigue syndrome. We are presenting a case of depression who was not responding to antidepressant therapy. Based on clinical history, diagnosis was changed to chronic fatigue syndrome and in view of prominent sleep disturbances, polysomnography was done. Based on sleep study data, diagnosis of periodic limb movement disorder was made and he was started on ropinirole, that improved his symptoms.

Obstructive sleep apnea (OSA) co-occurring with Kleine–Levin Syndrome (KLS) is a rare condition. We present the case of a middle-aged woman who presented with short lasting episodes of hypersomnia, anorexia, irritability, crying and symptoms of derealization. She was given antidepressants considering depression earlier with which she was not responding. After ruling out other potential causes for the same, diagnosis of KLS was made. Oxcarbazepine 450 mg/day led to resolution of symptoms. However, daytime sleepiness and fatigue persisted. Polysomnography suggested the presence of severe OSA which resolved with use of CPAP. Addition of CPAP to oxcarbazepine resolved symptoms completely.

High Performance Liquid Chromatography is a technique in analytical chemistry used to separate, identify and quantify each component in a mixture. The HPLC is suitable for a variety of clinical applications, including pharmaceutical development, legal application such as detecting the Presence of illicit drugs in urine & blood. High-performance liquid chromatography is a technique introduced for the accurate diagnosis of hemoglobinopathies, thalassemias & estimation of glycosylated hemoglobin. The advantage of the HPLC system is the excellent resolution, reproducibility & quantification of several normal & abnormal hemoglobin resulting in accurate diagnosis of thalassemia syndromes. HPLC technique which is used to separate the component in across the two equivalents phases i.e. stationary phases is solid or liuqid supported on a solid which is packed into a column while sample moves in along with mobile phase is liuqid or gas. The purpose of this study is to evaluate the HPLC technique in diagnosis of thalassemia syndromes and also correlate it with clinicohematological profile in these cases.

Tonsillar carcinoma metastasis to the myocardium is undermined with detection rate often occurring at autopsy or advance stage. A 60-year-old male with a 1-month history of right-sided facial pain and failed antibiotics therapy underwent head and neck CT scan that revealed a tonsillar mass. Tonsillar biopsy revealed squamous cell carcinoma, HPV-16 positive. PET-CT scan showed a significant activity in the right tonsillar mass along with prominent right level 2 lymph nodes and no distant disease. Definite surgery was deferred and he underwent 7 weeks of radiation therapy with concurrent weekly Cisplatin. PET scan 8 weeks later showed significant improvement in large right palatine tonsil mass; however, a new FDG-avid cardiac mass of right ventricle. An echocardiogram showed an ejection fraction of 59% and a large mass in the apical portion of the right ventricle. Cardiac MRI confirmed a 9 cm right ventricular mass. Complete resection of the cardiac mass was unsuccessful; a partial tumor debulking provided adequate sample for pathologic examination, which was consistent with metastatic squamous cell cancer, p16+, clinical-stage T4aN1M1. Surgical intervention was not performed; instead, he received a palliative radiation therapy to his right-sided cardiac mass with concurrent Keytruda immunotherapy. Unfortunately, the evening of successfully completing his last therapy, he was found unresponsive and subsequently expired. Although tonsillar carcinoma metastasis to the myocardium is rarely coupled with its atypical presentations, clinicians should consider early echocardiogram evaluation for possible metastatic disease so as to provide early interventions.

The underrepresentation of non-Europeans in human genetic studies so far has limited the diversity of individuals in genomic datasets and led to reduced medical relevance for a large proportion of the world’s population. Population-specific reference genome datasets as well as genome-wide association studies in diverse populations are needed to address this issue. Here we describe the pilot phase of the GenomeAsia 100K Project. This includes a whole-genome sequencing reference dataset from 1,739 individuals of 219 population groups and 64 countries across Asia. We catalogue genetic variation, population structure, disease associations and founder effects. We also explore the use of this dataset in imputation, to facilitate genetic studies in populations across Asia and worldwide., Using whole-genome sequencing data from 1,739 individuals, the GenomeAsia 100K Project catalogues genetic variation, population structure and disease associations to facilitate genetic studies in Asian populations and increase representation in genetics studies worldwide.

Systemic Lupus Erythematosus (SLE) and ANCA-associated vasculitis are classically thought to be separate diseases with different pathophysiologies. An overlap of these diseases has been reported few times in the literature. We present a unique case of a Caucasian male in his third decade of life, without a previous personal or family history of autoimmune disease, with serological and biopsy findings of both diseases occurring simultaneously. ANCA, typically p-ANCA, can be detected in up to 30% of SLE patients and can be higher with renal involvement. Patients with overlap syndrome have increased complications and higher mortality rates than those with either disease alone. Our patient was found to have necrotizing and crescentic glomerulonephritis, most consistent with ANCA vasculitis, specifically microscopic polyangitis with MPO positive staining. The biopsy also revealed abundant immune-complex deposits consistent with WHO class V diffuse membranous lupus glomerulonephritis. These diseases are typically seen in young to middle aged females, and given the rarity of this case, biopsy findings were confirmed by two pathologists from separate institutions. Presentations of autoimmune diseases and vasculitis can be multi-systemic. Immediate action and appropriate work up with a multidisciplinary team is required for optimal patient care. Our patient displayed pulmonary-renal involvement in addition to systemic features such as fevers, myalgia and profound anemia. Considering overlap syndromes, especially in patients with underlying connective tissue disease or systemic vasculitis, is vital for the prevention of excess morbidity in this population.

Transient protein expression is a useful technique for investigating the protein localization and functional analysis of stress responses in rice plants. Currently, available methods for in planta transient expression analysis include Agrobacterium-mediated transformation, protoplast transformation using polyethylene glycol or electroporation, and biolistic bombardment expression which have several disadvantages and are not well suited for the rice. Therefore, development of a method for rapid and efficient analysis of protein expression, subcellular localization, pathogen effector screening, and protein–protein interaction in rice is required. We developed a protocol for in planta gene expression analysis in sliced rice sheath cells by modifying and optimizing the biolistic particle bombardment technique. By obtaining thin sections (~400 μm) of rice sheath cells, auto-fluorescence from chlorophyll was eliminated. This system was validated through the localization of marker genes specifically expressed in nuclei, plasma membranes, and tonoplast. In addition, high transformation efficiency of 30% was achieved. Therefore, this protocol provides a new and rapid method for transient gene expression assay in rice. Protein secretion was examined in rice sheath cells using predicted secretory proteins from rice blast fungus, indicating that this method is applicable to plant–microbe interaction studies. The transient expression protocol established here is well optimized for protein localization, secretion, and host–pathogen protein interaction studies in rice. A typical experiment can be completed in three days.

Introduction: The last decade has yielded significant developments in the field of proteomics, especially in mass spectrometry (MS) and data analysis tools. In particular, a shift from gel-based to MS-based proteomics has been observed, thereby providing a platform with which to construct proteome atlases for all life forms. Nevertheless, the analysis of plant proteomes, especially those of samples that contain high-abundance proteins (HAPs), such as soybean seeds, remains challenging. Areas covered: Here, we review recent progress in soybean seed proteomics and highlight advances in HAPs depletion methods and peptide pre-fractionation, identification, and quantification methods. We also suggest a pipeline for future proteomic analysis, in order to increase the dynamic coverage of the soybean seed proteome. Expert opinion: Because HAPs limit the dynamic resolution of the soybean seed proteome, the depletion of HAPs is a prerequisite of high-throughput proteome analysis, and owing to the use of two-dimensional gel electrophoresis-based proteomic approaches, few soybean seed proteins have been identified or characterized. Recent advances in proteomic technologies, which have significantly increased the proteome coverage of other plants, could be used to overcome the current complexity and limitation of soybean seed proteomics.

Chronically activated CD4+ T cells drive uncontrolled inflammation, leading to tissue damage in various autoimmune disorders, such as rheumatoid arthritis (RA). Investigation of the molecular mechanisms involved in RA and recent analysis of transcriptomic profiles has implicated members of the nuclear receptor (NR) superfamily in RA. NRs are required for the development, differentiation, and effector function of CD4+ T cells; therefore, it is thought that NRs are important in shaping the CD4+ T cell repertoire and associated inflammation in RA. Despite their relevance, the full potential of the NR superfamily in RA, either as biomarkers or disease targets, has not been harnessed. To gain insight on the NR members that are closely associated with RA disease activity, we generated an expression atlas for the NR superfamily in CD4+ T cells isolated either in a steady state or over the course of collagen-induced arthritis mouse model of RA. We observed discrete expression patterns among the NR superfamily during the disease stages. NRs that instigate anti-inflammatory programs underwent major downregulation during disease onset; however, during the fully developed disease stage we noticed that NRs that induce proinflammatory programs had reduced transcript levels. These animal findings corroborated well with the expression patterns of NRs in clinical samples obtained from RA patients. Furthermore, we observed that targeting NRs using synthetic ligands alleviates the progression of collagen-induced arthritis. Overall, our data demonstrates the potential of the NR superfamily as novel therapeutic targets for the treatment of autoimmune disorders.

Datura, a wild plant from solanaceae family is very well known for its poisonous and medicinal properties. It contains a wide variety of phytoconstituents such as alkaloids, essential oils, flavonoids, tannins, steroids, glycosides etc. They are responsible for various medicinal properties. Wide variety of pharmacological activities of different species of datura have been reported so far such as anti-inflammatory, anti-diarrhoeal, hypoglycemic activity, anti-viral activity etc. Daturastramonium has been used for curing various ailments including ulcer, wounds, gout, fever, asthma, toothache etc. The aim of present study is to investigate the anti-inflammatory activity of seed extract of Daturastramonium against carrageenan induced paw edema model in albino wistar rats. Keywords: Daturastramonium, Phytoconstituents, Hypoglycemic, Solanaceae, Anti-inflammatory activity.

Summary Introduction Aim of this study was to see the effect of quadruple hamstring tendon graft diameter on knee stability, functional outcome, and graft rupture risk after ACL reconstruction. Method This study had two parts retrospective part and prospective part. In retrospective part, 18 athletes who underwent revision ACL reconstruction surgery between years 2008 and 2015 were identified from the computerized database. In prospective part, 103 athletes who underwent primary ACL reconstruction were enrolled in the study and divided into two groups depending upon their quadruple hamstring tendon graft diameter – group A (graft diameter Results In retrospective study, l6/18 athletes who underwent revision ACL surgery had graft size 0.05). Conclusion Graft size of

Restless legs syndrome is a common condition affecting nearly 2% Indian population. Certain questionnaires for screening or diagnostic purpose have been developed in the West, and they were translated to Hindi. However, those questionnaires have been found to have limitations in Indian context considering the cultural effect on vocabulary for the description of symptoms. Based on the IRLSSG criteria, a 12-item questionnaire was developed. Most of the items had dichotomous responses. This questionnaire was tested in subjects having RLS. Control group consisted of subjects suffering from clinically significant anxiety, myalgia of legs, arthralgia in legs, burning feet syndrome, nocturnal leg cramps and somatic symptoms disorder persistent pain type; conditions that could mimic RLS. Face validity and content validity were examined. Internal consistency of the questionnaire was assessed. Diagnostic outcome from the new questionnaire was assessed against clinical diagnosis, which is considered as gold standard at present. This study included 49 cases of RLS and 44 subjects in control group. Female preponderance was noted in both groups (69.4% in RLS group and 63.6% in control group; P = 0.55). Mean age of subjects in both groups was comparable (38.1 ± 2.3 years in RLS and 40.1 ± 2.5 years in control group; P = 0.10). New diagnostic questionnaire had sensitivity of 73.4% (95% CI = 58.9–85.0) and specificity of 88.6% (95% CI = 75.4–96.2). Positive predictive value was 87.8% (95% CI = 75.6–94.3%) and negative predictive value was 75% (95% CI = 65–82.8) with the diagnostic accuracy of 80.6% (95% CI = 71.1–88.1). New questionnaire correlated well with clinical diagnosis (r = 0.62; P

ResumoFraturas acetabulares são lesões graves e desafiadoras para cirurgiões ortopédicos. As abordagens anterior e posterior foram descritas para a fixação dessas fraturas. A técnica de Stoppa modificada é considerada uma alternativa à abordagem anterior, que fornece acesso à pelve pelo interior da cavidade. O objetivo do presente artigo é revisar a literatura disponível sobre o uso da abordagem de Stoppa modificada em fraturas de acetábulo. Os dados disponíveis sugerem que a abordagem de Stoppa modificada é útil em fraturas anteriores de acetábulo e em algumas fraturas posteriores, especialmente aquelas nas quais o reforço da parede medial se faz necessário.

Previously, we reported a novel Magnaporthe oryzae- secreted protein MSP1, which triggers cell death and pathogen-associated molecular pattern (PAMP)-triggered immune (PTI) responses in rice. To investigate the MSP1 induced defense response in rice at the protein level, we employed a label-free quantitative proteomic approach, in parallel with flg22 treatment, which is a well-known elicitor. Exogenous application of MSP1 to rice leaves induced an oxidative burst, MAPK3/6 activation, and activation of pathogenesis-related genes (DUF26, PBZ, and PR-10). MaxQuant based label free proteome analysis led to the identification of 4167 protein groups of which 433 showed significant differences in response to MSP1 and/or flg22 treatment. Functional annotation of the differential proteins showed that majority of the proteins related to primary, secondary, and lipid metabolism were decreased, while proteins associated mainly with the stress response, post-translational modification and signaling were increased in abundance. Moreover, several peroxidases and receptor kinases were induced by both the elicitors, highlighting their involvement in MSP1 and flg22 induced signaling in rice. Taken together, the results reported here contribute to our understanding of MSP1 and flg22 triggered immune responses at the proteome level, thereby increasing our overall understanding of PTI signaling in rice. BIOLOGICAL SIGNIFICANCE: MSP1 is a M. oryzae secreted protein, which triggers defense responses in rice. Previous reports have shown that MSP1 is required for the pathogenicity of rice blast fungus, however, the exact mechanism of its action and its downstream targets in rice are currently unknown. Identification of the downstream targets is required in order to understand the MSP1 induced signaling in rice. Moreover, key proteins identified could also serve as potential candidates for the generation of disease resistance crops by modulating stress signaling pathways. Therefore, here we employed, for the first time, a label-free quantitative proteomic approach to investigate the MSP1 induced signaling in rice together with flg22. Functional annotation of the differential proteins showed that majority of the proteins related to primary, secondary, and lipid metabolism were decreased, while proteins related to the defense response, signaling and ROS detoxification were majorly increased. Thus, as an elicitor, recombinant MSP1 proteins could be utilized to inducing broad pathogen resistance in crops by priming the local immune responses.

Chitinases are glycosyl hydrolases which hydrolyse β-1,4-glycosidic bonds between N-acetylglucosamine residues of chitin. Seabuckthorn (Hippophae rhamnoides), a cold desert plant, is a storehouse of many cold-tolerant proteins including dual-functioning antifreeze proteins (AFPs) possessing both hydrolytic and antifreeze activities. Herein, we report the purification and characterization of antifreeze chitinases from seedlings grown in laboratory conditions. Chitin-affinity chromatography led to homogenous purification of two acidic chitinases HrS CHT1a (33 kDa) and HrS CHT1b (38 kDa) from seedlings. Antifreeze activity of purified AFPs was confirmed by the formation of hexagon-shaped ice crystals using nanolitre osmometer. Similarly, sucrose sandwich splat assay also confirmed their ice recrystallization inhibition activity (1.6-fold decrease in mean ice crystals). The chitinase activity of AFPs was confirmed by chitin hydrolytic assay where higher activity (1.8-fold) was observed in HrS CHT1b (500 U/mg) than HrS CHT1a (222 U/mg). MS identification showed homology of HrS CHT1b with provicilin while HrS CHT1a was identified as uncharacterized protein. In silico analysis showed that purified AFPs differ significantly in biochemical properties which suggests their different physiological roles. Protein association network analysis using string showed interaction of HrS CHT1b with enzymes involved majorly in pathogenic protection (pectinesterase, glycosyl hydrolase protein with chitinase domain). However, HrSCHT1a showed interaction with proteins associated with growth and energy regulation (glycine and purine synthesis, vitamin B metabolism) thereby indicating differential functional roles of both the chitinases. Conserved domain analysis also supported that these AFPs are multifunctional and exhibit differential regulatory roles in enabling the plant growth and defense responses. Further validation of these targets may open gates for commercial utilization of this plant growing abundantly in the Himalayan regions of India for protection of freeze-susceptible crops or biomedical applications.

Jerusalem artichoke (JA) tubers are an important bio-economy developing crop because of its invaluable bioproducts in both food and biofuel aspects. However, the molecular mechanism of its tuberization, and the differences among different cultivars have been little studied to date. Therefore, here we selected PJA, DJA, and HJA cultivars of JA tubers, showing variations in their tuber epidermal pigmentation, underground tuberization, and inulin content. A comparative proteome analysis led to the identification of 402 proteins in the tubers of which 114 were significantly modulated among different cultivars. Gene Ontology (GO) analysis showed proteins related to the biosynthesis of amino acids and carbohydrate metabolism were differentially modulated in the tubers of three cultivars. Results from the inulin content measurement and proteome analysis suggest that Sucrose:sucrose 1-fructosyltransferase (1-SST) prioritizes inulin biosynthesis rather than rate-limiting enzyme fructan:fructan 1-fructosyltransferases (1-FFT). Furthermore, we confirmed the relationship between transcript-protein expression levels was in discord within inulin biosynthesis enzymes 1-SST and 1-FFT with the terms in previous RT-qPCR results using the same tubers. Our data represent the first report of comparative tuber proteome profiling of different JA and provide the metabolic and molecular basis for understanding carbohydrate metabolism in the tuber tissue.

Background: Ginseng is one of the well-known medicinal plants, exhibiting diverse medicinal effects. Its roots possess anticancer and antiaging properties and are being used in the medical systems of East Asian countries. It is grown in low-light and low-temperature conditions, and its growth is strongly inhibited at temperatures above 25°C. However, the molecular responses of ginseng to heat stress are currently poorly understood, especially at the protein level. Methods: We used a shotgun proteomics approach to investigate the effect of heat stress on ginseng leaves. We monitored their photosynthetic efficiency to confirm physiological responses to a high-temperature stress. Results: The results showed a reduction in photosynthetic efficiency on heat treatment (35°C) starting at 48 h. Label-free quantitative proteome analysis led to the identification of 3,332 proteins, of which 847 were differentially modulated in response to heat stress. The MapMan analysis showed that the proteins with increased abundance were mainly associated with antioxidant and translation-regulating activities, whereas the proteins related to the receptor and structural-binding activities exhibited decreased abundance. Several other proteins including chaperones, G-proteins, calcium-signaling proteins, transcription factors, and transfer/carrier proteins were specifically downregulated. Conclusion: These results increase our understanding of heat stress responses in the leaves of ginseng at the protein level, for the first time providing a resource for the scientific community. Keywords: High temperature, Panax ginseng, Photosynthetic efficiency, Shotgun proteomics

Solid pseudopapillary neoplasm (SPN) is rare pancreatic neoplasm. Predominantly in young female, present with abdominal lump and pain. These tumors are indolent in nature. In our case series, 8 cases in 6 years period (2012 to 2018), with one of them is unusual site in retroperitoneum. Mean age of presentation was 25.6 years. Presenting symptom was dull aching pain (80%), lump in upper abdomen (65%). Mean size was 11.6 cm on imaging abdomen. All patients underwent surgery, one patient underwent preoperative FNAC due to unusual location. Mean postoperative hospital stay was 13.9 days with no mortality. By immunohistochemistry, all cases stained positive for vimentin, CD 10 and all were negative for cytokeratin and Ki67

The aim of the present work is to understand the carbon deposition during graphene growth in plasma enhanced chemical vapor deposition system containing Ar/C2H2/H2 gas mixture and to optimize the process parameters for the enhanced growth of graphene. In this regard, many numerical simulations have been carried out using two-dimensional axis-symmetrical inductively coupled plasma module in COMSOL multi physics 5.2a simulation software. From the simulation outcomes, it is found that the electron density, electron energy density, electric potential, and collisional power losses decrease with an increase in temperature. The number densities of various dominant ions were found to decrease and number densities of dominant neutrals were found to increase with an increase in temperature. During the carbon deposition, the formation of non-uniform horizontal graphene layer has been observed along the substrate and vertically oriented graphene sheet has been observed at the edges of the substrate. It is found that the thickness of horizontal graphene along the substrate and height of vertical graphene at the edges of the substrate increases with an increase in gas temperature. Moreover, the reduction in the carbon deposition on the substrate (growth of parallel graphene) and enhanced growth of vertical graphene sheet have been observed on applying substrate biasing. Our numerical simulation results are in good agreement with existing experimental observations and confirms the adequacy of the computational and simulation approach.

Background: Serum interleukin (IL)-6 has been found to be associated with sleep quality, mood, and survival in patients with solid tumors. Results in these studies were confounded by knowledge of diagnosis to study subjects. Moreover, such data among subjects with hematological malignancies and data regarding restless legs syndrome is limited. The present study was, therefore, conducted to assess the sleep quality, depression, and restless leg syndrome in hematological malignancies and to study if there is any role of IL6 associated with it. Methods: Sixty-six subjects having hematological malignancy were included in this study after excluding the potential confounders. Sleep quality was examined using Pittsburg Sleep Quality Index, depression by the Patient Health Questionnaire-9. Diagnosis of RLS was made through clinical examination. Serum for measurement of IL-6 was collected at baseline and after 1 month of initiation of chemotherapy. Patients were followed up for 6 months. Results: Average age of study subjects was 50.16 years with male predominance. Nearly 22.7% had clinical depression, 28.8% had poor quality sleep, and restless legs syndrome (RLS) was reported in 6.1% cases. Nearly 22.7% patients died at 6 months. Disturbed sleep at baseline was associated with depression (odds ratio [OR] =7.89) and poor 6 months survival. Serum IL-6 did not show any association with sleep quality, restless-legs-syndrome, and depression. However, baseline high level of serum IL-6 (OR = 26.06) and low level after chemotherapy (OR = 0.03) were associated with poor survival at 6 months. Conclusion: Poor quality sleep, depression, and RLS are prevalent among adult subjects with hematological malignancies. Sleep disturbance, high pretreatment inflammatory and lowering of inflammatory load after chemotherapy increase likelihood for poor prognosis. Serum IL-6 did not show any association with sleep quality, restless legs syndrome and depression.

Pathogen-associated molecular patterns (PAMPs) play a key role in triggering PAMPs triggered immunity (PTI) in plants. In the case of the rice-Magnaporthe oryzae pathosystem, fewer PAMPs and their pattern recognition receptors (PRRs) have been characterized. Recently, a M. oryzae snodprot1 homolog protein (MSP1) has been identified that functions as PAMP and triggering the PTI responses in rice. However, the molecular mechanism underlying MSP1-induced PTI is currently elusive. Therefore, we generated MSP1 overexpressed transgenic lines of rice, and a tandem mass tag (TMT)-based quantitative membrane proteomic analysis was employed to decipher the potential MSP1-induced signaling in rice using total cytosolic as well as membrane protein fractions. This approach led to the identification of 8033 proteins of which 1826 were differentially modulated in response to overexpression of MSP1 and/or exogenous jasmonic acid treatment. Of these, 20 plasma membrane-localized receptor-like kinases (RLKs) showed increased abundance in MSP1 overexpression lines. Moreover, activation of proteins related to the protein degradation and modification, calcium signaling, redox, and MAPK signaling was observed in transgenic lines expressing MSP1 in the apoplast. Taken together, our results identified potential PRR candidates involved in MSP1 recognition and suggested the overview mechanism of the MSP1-induced PTI signaling in rice leaves. SIGNIFICANCE: In plants, recognition of pathogen pathogen-derived molecules, such as PAMPs, by plant plant-derived PRRs has an essential role for in the activation of PTI against pathogen invasion. Typically, PAMPs are recognized by plasma membrane (PM) localized PRRs, however, identifying the PM-localized PRR proteins is challenging due to their low abundance. In this study, we performed an integrated membrane protein enrichment by microsomal membrane extraction (MME) method and subsequent TMT-labeling-based quantitative proteomic analysis using MSP1 overexpressed rice. Based on these results, we successfully identified various intracellular and membrane membrane-localized proteins that participated in the MSP1-induced immune response and characterized the potential PM-localized PRR candidates in rice.

Ginseng (Panax ginseng C. A. Meyer), due to its relatively longer cultivation time, is often exposed to environmental stresses such as heat, salt, and drought. Particularly, salt-stress-derived oxidative damages greatly affect photosynthetic efficiency and consequently cause reduction of growth, development, and yield of ginseng. Thus, efforts have been made to understand the salt-stress-induced changes at proteome levels; however, the overall understanding of possible salt-responsive proteins in ginseng is still limited because of their low-abundance. A growing body of evidence suggests that plants secrete various low-abundant proteins localized in the intra- and extracellular spaces during stress conditions, and those proteins may have a key role for salt tolerance. Therefore, here, we report the ginseng fluids proteome to identify the potential salt-responsive proteins. This approach led to the identification of 261 secreted fluid proteins, and functional categorization revealed that identified proteins were majorly associated with photosynthesis, protein synthesis, cell binding, and various metabolisms. Further validation using qRT-PCR analysis showed similar expression profiles of heat-shock protein 70, glycosyl hydrolase 17, and fructose-bisphosphate aldolase class-I with proteome results. Overall, ginseng fluid proteomic analysis successfully identified the potential salt-responsive proteins, which might be helpful for understanding of salt-tolerance mechanisms in ginseng.

Parkinson's disease (PD) is a genetically heterogeneous neurodegenerative disease with poorly defined environmental influences. Genomic studies of PD patients have identified disease-relevant monogenic genes, rare variants of significance, and polygenic risk-associated variants. In this study, whole genome sequencing data from 90 young onset Parkinson's disease (YOPD) individuals are analyzed for both monogenic and polygenic risk. The genetic variant analysis identifies pathogenic/likely pathogenic variants in eight of the 90 individuals (8.8%). It includes large homozygous coding exon deletions in PRKN and SNV/InDels in VPS13C, PLA2G6, PINK1, SYNJ1, and GCH1. Eleven rare heterozygous GBA coding variants are also identified in 13 (14.4%) individuals. In 34 (56.6%) individuals, one or more variants of uncertain significance (VUS) in PD/PD-relevant genes are observed. Though YOPD patients with a prioritized pathogenic variant show a low polygenic risk score (PRS), patients with prioritized VUS or no significant rare variants show an increased PRS odds ratio for PD. This study suggests that both significant rare variants and polygenic risk from common variants together may contribute to the genesis of PD. Further validation using a larger cohort of patients will confirm the interplay between monogenic and polygenic variants and their use in routine genetic PD diagnosis and risk assessment.

Among the causes of acute surgical abdomen intestinal perforation and mesenteric ischemia are some of the leading causes of morbidity and mortality. Gastric perforation has a mortality rate of 20-30% and mesenteric ischemia has a mortality of 60%. The presence of both pathologies in the same patient at the same time is a rare association and very few cases have been reported till now. This association has been described in cases of polyarteritis nodosa. Here we are presenting our case in which no such vascular pathology was identified. We have tried to hypothesize the reason behind this rare association.

Brassinosteroids (BRs) play crucial roles in various biological processes, including plant developmental processes and response to diverse biotic and abiotic stresses. However, no information is currently available about this gene family in wheat (Triticum aestivum L.). In the present investigation, we identified the BZR gene family in wheat to understand the evolution and their role in diverse developmental processes and under different stress conditions. In this study, we performed the genome-wide analysis of the BZR gene family in the bread wheat and identified 20 TaBZR genes through a homology search and further characterized them to understand their structure, function, and distribution across various tissues. Phylogenetic analyses lead to the classification of TaBZR genes into five different groups or subfamilies, providing evidence of evolutionary relationship with Arabidopsis thaliana, Zea mays, Glycine max, and Oryza sativa. A gene exon/intron structure analysis showed a distinct evolutionary path and predicted the possible gene duplication events. Further, the physical and biochemical properties, conserved motifs, chromosomal, subcellular localization, and cis-acting regulatory elements were also examined using various computational approaches. In addition, an analysis of public RNA-seq data also shows that TaBZR genes may be involved in diverse developmental processes and stress tolerance mechanisms. Moreover, qRT-PCR results also showed similar expression with slight variation. Collectively, these results suggest that TaBZR genes might play an important role in plant developmental processes and various stress conditions. Therefore, this work provides valuable information for further elucidate the precise role of BZR family members in wheat.

The preparation of microsomal membrane proteins (MPs) is critically important to microsomal proteomics. To date most research studies have utilized an ultracentrifugation-based approach for the isolation and solubilization of plant MPs. However, these approaches are labor-intensive, time-consuming, and unaffordable in certain cases. Furthermore, the use of sodium dodecyl sulfate (SDS) and its removal prior to a mass spectrometry (MS) analysis through multiple washing steps result in the loss of proteins. To address these limitations, this study introduced a simple micro-centrifugation-based MP extraction (MME) method from rice leaves, with the efficacy of this approach being compared with a commercially available plasma membrane extraction kit (PME). Moreover, this study assessed the subsequent solubilization of isolated MPs in an MS-compatible surfactant, namely, 4-hexylphenylazosulfonate (Azo) and SDS using a label-free proteomic approach. The results validated the effectiveness of the MME method, specifically in the enrichment of plasma membrane proteins as compared with the PME method. Furthermore, the findings showed that Azo demonstrated several advantages over SDS in solubilizing the MPs, which was reflected through a label-free quantitative proteome analysis. Altogether, this study provided a relatively simple and rapid workflow for the efficient extraction of MPs with an Azo-integrated MME approach for bottom-up proteomics.

Introduction: Traumatic dislocation of hip associated with ipsilateral femur neck and acetabulum fracture is a rare and devastating injury as a result of high-energy trauma, with potential complications of femur head aseptic necrosis and hip joint degenerative arthritis. Patients, postoperatively, may encounter decreased functional outcomes and serious challenge, during activities of daily living. Management guidelines lack clarity, with possible options including fracture fragments fixation or hip joint replacement. Case Report: A 45-year-old patient was diagnosed with posterior dislocation of hip with ipsilateral femur neck and acetabulum fracture. Plan for emergent hip reduction and primary surgical fixation of fracture fragments was made. Intraoperatively, posterior wall acetabulum fracture was found to be excessively comminuted and non-amenable for fixation and femoral head was found to be avascularized. Subsequently, plan was changed to total hip replacement with acetabular defect reconstruction. At 1-year follow-up, no aseptic loosening was observed on radiographic views of pelvis, with total Harris Hip Score of 91. Conclusion: Early operative management for such complex injuries is a necessity. Definitive management in the form of primary fracture fixation/arthroplasty should be decided intraoperatively. Keywords: Femur neck, hip dislocation, acetabulum fracture, ipsilateral, case report.

21 pags., 12 figs., 4 tabs., The See Change survey was designed to make z > 1 cosmological measurements by efficiently discovering high-redshift Type Ia supernovae (SNe Ia) and improving cluster mass measurements through weak lensing. This survey observed twelve galaxy clusters with the Hubble Space Telescope (HST) spanning the redshift range z = 1.13-1.75, discovering 57 likely transients and 27 likely SNe Ia at z ~ 0.8-2.3. As in similar previous surveys, this proved to be a highly efficient use of HST for supernova observations; the See Change survey additionally tested the feasibility of maintaining, or further increasing, the efficiency at yet higher redshifts, where we have less detailed information on the expected cluster masses and star formation rates. We find that the resulting number of SNe Ia per orbit is a factor of ~8 higher than for a field search, and 45% of our orbits contained an active SN Ia within 22 rest-frame days of peak, with one of the clusters by itself yielding 6 of the SNe Ia. We present the survey design, pipeline, and supernova discoveries. Novel features include fully blinded supernova searches, the first random forest candidate classifier for undersampled IR data (with a 50% detection threshold within 0.05 mag of human searchers), real-time forward-modeling photometry of candidates, and semi-automated photometric classifications and follow-up forecasts. We also describe the spectroscopic follow-up, instrumental in measuring host galaxy redshifts. The cosmology analysis of our sample will be presented in a companion paper. * Based on observations with the NASA/ESA Hubble Space Telescope, obtained at the Space Telescope Science Institute, which is operated by AURA, Inc., under NASA contract NAS 5-26555, under programs 13677, 14327., Based in part on observations obtained at the Gemini Observatory, which is operated by the Association of Universities for Research in Astronomy, Inc., under a cooperative agreement with the NSF on behalf of the Gemini partnership: the National Science Foundation (United States), National Research Council (Canada), CONICYT (Chile), Ministerio de Ciencia, Tecnología e Innovación Productiva (Argentina), Ministério da Ciência, Tecnologia e Inovação (Brazil), and Korea Astronomy and Space Science Institute (Republic of Korea). Based on observations collected at the Table 4. European Organisation for Astronomical Research in the Southern Hemisphere under ESO program(s) 294.A-5025(A), 095.A-0830(A, B, C), 096.A-0926(B, C), 097.A-0442(A, B, C), and 0100.A-0851(A). G.W. acknowledges support from the National Science Foundation through grant AST-1517863, by HST program numbers GO-13677/14327.01 and GO-15294, and by grant No. 80NSSC17K0019 issued through the NASA Astrophysics Data Analysis Program (ADAP). G.A. and R.G. acknowledge support from HST program NASA HST-GO14163.002-A, and by grant No. NNH16AC25I issued through NASA ADAP. M. J. J. acknowledges support for the current research from the National Research Foundation (NRF) of Korea under the programs 2017R1A2B2004644 and 2020R1A4A2002885. H. Hildebrandt is supported by a Heisenberg grant of the Deutsche Forschungsgemeinschaft (Hi 1495/5-1) as well as an ERC Consolidator Grant (No. 770935). Support for program numbers GO-13677/14327.01 and GO-15294 was provided by NASA through a grant from the Space Telescope Science Institute, which is operated by the Association of Universities for Research in Astronomy, Incorporated, under NASA contract NAS5-26555. This work was also partially supported by the Office of Science, Office of High Energy Physics, of the U.S. Department of Energy, under contract no. DE-AC02-05CH11231. Facilities: Hubble Space Telescope, Keck:I (LRIS), Keck:I (MOSFIRE), VLT, Gemini, GTC, Subaru. Software: astropy (Astropy Collaboration 2013), DrizzlePac (Gonzaga et al. 2012), iPython (Pérez & Granger 2007), Matplotlib (Hunter 2007), Numpy (van der Walt et al. 2011), SEP (Barbary 2016), scikit-learn (Pedregosa et al. 2011), SciPy