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1.
Braz. j. biol ; 83: e243874, 2023. graf
Artigo em Inglês | LILACS-Express | MEDLINE, LILACSEXPRESS | ID: biblio-1285606

RESUMO

Abstract In recent days, cheapest alternative carbon source for fermentation purpose is desirable to minimize production cost. Xylanases have become attractive enzymes as their potential in bio-bleaching of pulp and paper industry. The objective of the present study was to identify the potential ability on the xylanase production by locally isolated Bacillus pumilus BS131 by using waste fiber sludge and wheat bran media under submerged fermentation. Culture growth conditions were optimized to obtain significant amount of xylanase. Maximum xylanase production was recorded after 72 hours of incubation at 30 °C and 7 pH with 4.0% substrate concentration. In the nutshell, the production of xylanase using inexpensive waste fiber sludge and wheat-bran as an alternative in place of expensive xylan substrate was more cost effective and environment friendly.


Resumo Nos últimos dias, a fonte alternativa de carbono mais barata para fins de fermentação é desejável para minimizar o custo de produção. As xilanases têm se tornado enzimas atraentes como seu potencial no biobranqueamento da indústria de papel e celulose. O objetivo do presente estudo foi identificar a capacidade potencial na produção de xilanase por Bacillus pumilus BS131 isolado localmente usando lodo de fibra residual e farelo de trigo em meio de fermentação submersa. As condições de crescimento da cultura foram otimizadas para obter uma quantidade significativa de xilanase. A produção máxima de xilanase foi registrada após 72 horas de incubação a 30 °C e pH 7 com concentração de substrato de 4,0%. Resumindo, a produção de xilanase usando lodo de fibra residual de baixo custo e farelo de trigo como uma alternativa no lugar do substrato de xilano caro foi mais econômica e ecológica.

2.
Braz. j. biol ; 83: e250179, 2023. graf
Artigo em Inglês | LILACS-Express | MEDLINE, LILACSEXPRESS | ID: biblio-1339372

RESUMO

Abstract Diabetes mellitus (DM) is a non-communicable disease throughout the world in which there is persistently high blood glucose level from the normal range. The diabetes and insulin resistance are mainly responsible for the morbidities and mortalities of humans in the world. This disease is mainly regulated by various enzymes and hormones among which Glycogen synthase kinase-3 (GSK-3) is a principle enzyme and insulin is the key hormone regulating it. The GSK-3, that is the key enzyme is normally showing its actions by various mechanisms that include its phosphorylation, formation of protein complexes, and other cellular distribution and thus it control and directly affects cellular morphology, its growth, mobility and apoptosis of the cell. Disturbances in the action of GSK-3 enzyme may leads to various disease conditions that include insulin resistance leading to diabetes, neurological disease like Alzheimer's disease and cancer. Fluoroquinolones are the most common class of drugs that shows dysglycemic effects via interacting with GSK-3 enzyme. Therefore, it is the need of the day to properly understand functions and mechanisms of GSK-3, especially its role in glucose homeostasis via effects on glycogen synthase.


Resumo O diabetes mellitus (DM) é uma doença não transmissível em todo o mundo, na qual existe nível glicêmico persistentemente alto em relação à normalidade. O diabetes e a resistência à insulina são os principais responsáveis ​​pelas morbidades e mortalidades de humanos no mundo. Essa doença é regulada principalmente por várias enzimas e hormônios, entre os quais a glicogênio sintase quinase-3 (GSK-3) é uma enzima principal e a insulina é o principal hormônio que a regula. A GSK-3, que é a enzima-chave, normalmente mostra suas ações por vários mecanismos que incluem sua fosforilação, formação de complexos de proteínas e outras distribuições celulares e, portanto, controla e afeta diretamente a morfologia celular, seu crescimento, mobilidade e apoptose do célula. Perturbações na ação da enzima GSK-3 podem levar a várias condições de doença que incluem resistência à insulina que leva ao diabetes, doenças neurológicas como a doença de Alzheimer e câncer. As fluoroquinolonas são a classe mais comum de drogas que apresentam efeitos disglicêmicos por meio da interação com a enzima GSK-3. Portanto, é necessário hoje em dia compreender adequadamente as funções e mecanismos da GSK-3, principalmente seu papel na homeostase da glicose via efeitos na glicogênio sintase.

3.
Braz. j. biol ; 82: e243283, 2022. tab, graf
Artigo em Inglês | LILACS-Express | MEDLINE, LILACSEXPRESS | ID: biblio-1278505

RESUMO

ABSTRACT Infectious agents cause serious diseases in humans worldwide and are responsible for the high rate of morbidity and mortality. The prevalence and epidemiology of infectious disease (HCV) in the hospital visited patients referred by the physicians through the initial findings and their associated risk factors were studied in Swat. The data of 174 infected patients were collected during the period of 2015 to 2017 from two clinical laboratories of Tehsil Matta Swat. Inform consent form was taken before blood collection. After taking informed consent blood samples were collected and ICT test was performed and then ICT positive cases were conform through PCR. A total of 174 ICT positive samples [106 male and 68 females] were included in this study. Age was considered from 10 to 72 years. Of the 174 ICT strip positive, 99 [63 males, 36 females] were confirmed through PCR. The prevalence rate was recorded 56.89%. I.V/I.M injection was recorded in 100% of the individuals. Visits to the barber shop was reported in (58%) of the individuals, married individuals were (81.0), surgical operation was reported in (44.8%), sharing toothbrush was observed in (29.9%), piercing was reported in (39.7%), family history was reported in (26.4%), dental treatment was observed in (21.8%), jaundice were (13.2%) and tattooing was (1.7%). Blood transfusion, surgical operations, Jaundice, family history and dental treatment were found significant risk factors for acquiring HCV infection. It was concluded that proper implementation of precautionary measures should be needed to control the spread of HCV in far near future.


RESUMO Agentes infecciosos causam doenças graves em humanos em todo o mundo, e são responsáveis pelo alto índice de morbimortalidade. A prevalência e a epidemiologia das doenças infecciosas no hospital que atendeu pacientes encaminhados pelos médicos por meio dos achados iniciais e seus fatores de risco associados foram estudadas em Peshawar. Os dados de 174 pacientes infectados foram coletados durante o período de 2015 a 2017 oriundos de dois laboratórios clínicos de Tehsil Matta Swat. O formulário de consentimento informado foi obtido antes da coleta de sangue. Após a obtenção do consentimento informado, foram coletadas amostras de sangue e foi realizado o teste ICT e, em seguida, os casos ICT positivos foram confirmados por PCR. Um total de 174 amostras ICT positivas [106 homens e 68 mulheres] foi incluído neste estudo. A idade considerada foi de 10 a 72 anos. Das 174 tiras de ICT positivas, 99 casos [63 homens, 36 mulheres] foram confirmados por PCR. A taxa de prevalência foi de 56,89%. A injeção IV / IM foi registrada em 100% dos indivíduos. A visita à barbearia foi relatada em (58%) dos indivíduos, os números de casados foram (81,0%), e a operação cirúrgica foi relatada em (44,8%), o compartilhamento de escova de dente foi observado em (29,9%), o piercing foi relatado em (39,7%), antecedentes familiares foram relatados em (26,4%), tratamento odontológico em (21,8%), icterícia (13,2%) e tatuagem em (1,7%). Transfusão de sangue, operações cirúrgicas, icterícia, histórico familiar e tratamento odontológico foram fatores de risco significativos para adquirir infecção por Vírus da Hepatite C (VHC). Concluiu-se que a implementação adequada de medidas de precaução deve ser necessária para controlar a propagação do VHC em um futuro próximo.

4.
Neurosurg Rev ; 2021 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-34613526

RESUMO

The history of academic research on ependymoma is expansive. This review summarizes its history with a bibliometric analysis of the 100 most cited articles on ependymoma. In March 2020, we queried the Web of Science database to identify the most cited articles on ependymoma using the terms "ependymoma" or "ependymal tumors," yielding 3145 publications. Results were arranged by the number of times each article was cited in descending order. The top 100 articles spanned across nearly a century; the oldest article was published in 1924, while the most recent was in 2017. These articles were published in 35 unique journals, including a mix of basic science and clinical journals. The three institutions with the most papers in the top 100 were St. Jude Children's Research Hospital (16%), the University of Texas MD Anderson Cancer Center (6%), and the German Cancer Research Center (5%). We analyzed the publications that may be considered the most influential in the understanding and treatment management of ependymoma. Studies focused on the molecular classification of ependymomas were well-represented among the most cited articles, reflecting the field's current area of focus and its future directions. Additionally, this article also offers a reference for further studies in the ependymoma field.

5.
Artigo em Inglês | MEDLINE | ID: mdl-34613552

RESUMO

PURPOSE OF REVIEW: Recent efforts to characterize hematologic cancers with genetic and molecular detail have largely relied on mutational profiling via next-generation sequencing (NGS). The application of NGS-guided disease prognostication and clinical decision making requires a basic understanding of sequencing advantages, pitfalls, and areas where clinical care might be enhanced by the knowledge generated. This article identifies avenues within the landscape of adult acute lymphoblastic leukemia (ALL) where mutational data hold the opportunity to enhance understanding of disease biology and patient care. RECENT FINDINGS: NGS-based assessment of measurable residual disease (MRD) after ALL treatment allows for a sensitive and specific molecular survey that is at least comparable, if not superior, to existing techniques. Mutational assessment by NGS has unraveled complex signaling networks that drive pathogenesis of T-cell ALL. Sequencing of patients with familial clustering of ALL has also identified novel germline mutations whose inheritance predisposes to disease development in successive generations. While NGS-based assessment of hematopoietic malignancies often provides actionable information to clinicians, patients with acute lymphoblastic leukemia are left underserved due to a lack of disease classification and prognostication schema that integrate molecular data. Ongoing research is positioned to enrich the molecular toolbox available to clinicians caring for adult ALL patients and deliver new insights to guide therapeutic selection, monitor clinical response, and detect relapse.

6.
J Card Surg ; 2021 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-34628679

RESUMO

INTRODUCTION: Aortic stenosis (AS) is the most common degenerative valvular heart disease that can affect left ventricular functions. Tp-e interval and Tp-e/QT ratio is a novel repolarization marker which is associated with adverse cardiovascular events in several cardiovascular diseases. In our study, our aim is to investigate the prognostic effect of Tp-e interval, Tp-e/QT and Tp-e/QTc ratios on mortality in patients who underwent successful surgical aortic valve replacement (AVR). METHODS: A total of three hundred seventy-five patients undergoing successful surgical AVR were included in this study. Then, patients were divided into two groups according to mortality as group 1 without mortality (342 patients) and group 2 with mortality (33 patients). Tp-e interval, Tp-e/QT, and Tp-e/QTc ratios were calculated for both groups. RESULTS: Tp-e interval (71 (63.7-77); 86 (84-88), p < .001), Tp-e/QT ratio (0.19 (0.17-0.20); 0.23 (0.22-0.23), p < .001) and Tp-e/QTc ratio (0.17 ± 0.02; 0.21 ± 0.01, p < .001) were higher in group 2 compared to group 1. In multivariate logistic regression analyses Tp-e interval (odds ratio [OR]: 1.315, 95% confidence interval [CI]: 1.203-1.437, p < .001), Tp-e/QT ratio (OR: 7.334, 95% CI: 3.274-1.643, p < .001) and Tp-e/QTc ratio (OR: 2.567, 95% CI: 4.106-1.605, p < .001) were found to be independent predictors of mortality. Additionally, a Kaplan-Meier survival analysis also revealed that long term survival was found to be significantly decreased in patients with higher Tp-e/QT ratio (Log-Rank p < .001) and Tp-e/QTc ratio (Log-Rank p < .001). CONCLUSION: Tp-e interval, Tp-e dispersion, Tp-e/QT, and Tp-e/QTc ratios are associated with worse prognosis after surgical AVR in patients with severe AS. All of them are also independent predictors of mortality.

7.
J Neurosurg ; : 1-6, 2021 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-34624849

RESUMO

OBJECTIVE: The surgical management of large and complex tumors of the posterior fossa poses a formidable challenge in neurosurgery. The standard retrosigmoid craniotomy approach has been performed at most neurosurgical centers; however, the retrosigmoid approach may not provide enough working space without significant retraction of the cerebellum. The transsigmoid approach provides wider and shallower surgical fields; however, there have been few clinical and no cadaveric studies on its usefulness. In the present study, the authors describe the transsigmoid approach in clinical cases and cadaveric specimens. METHODS: For the clinical study, the authors retrospectively reviewed the medical records and operative charts of patients who had been surgically treated for parabrainstem tumors using the transsigmoid approach between 1997 and 2019. They analyzed patient demographic and clinical data, as well as surgical and clinical outcomes. In the cadaveric study, they compared the surgical views obtained in different approaches (retrosigmoid, presigmoid, retrolabyrinthine, and transsigmoid) and measured the sigmoid sinus width at the level of the endolymphatic sac and the distance between the anterior edge of the sigmoid sinus and the endolymphatic sac on 35 sides in 19 cadaveric specimens. RESULTS: A total of 21 patients (6 males and 15 females) with a mean age of 42.2 (range 15-67) years were included in the clinical study. Eleven patients had meningioma, 7 had vestibular schwannoma, 2 had hemangioblastoma, and 1 had epidermoid cyst. Gross-total, near-total, and subtotal removal were achieved in 7 (33.3%), 3 (14.3%), and 11 (52.4%) patients, respectively. In the cadaveric study, 19 cadaveric specimens were used. The sigmoid sinus was cut in the middle, and the incision was extended from the retrosigmoid to the presigmoid dura. The dura was then retracted upward and downward like opening a door. The results indicated that this technique can widen the operative field anteriorly by approximately 2 cm as compared to the retrosigmoid approach and provides a better view anterior to the brainstem. CONCLUSIONS: The transsigmoid approach is useful for complex parabrainstem tumors in the posterior fossa because it provides a wider and shallower operative view with less retraction of the cerebellum. This enables safer tumor removal with less damage to important structures in the posterior fossa, resulting in better operative and clinical outcomes.

8.
PLoS One ; 16(10): e0257997, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34648513

RESUMO

Conventional testing and diagnostic methods for infections like SARS-CoV-2 have limitations for population health management and public policy. We hypothesize that daily changes in autonomic activity, measured through off-the-shelf technologies together with app-based cognitive assessments, may be used to forecast the onset of symptoms consistent with a viral illness. We describe our strategy using an AI model that can predict, with 82% accuracy (negative predictive value 97%, specificity 83%, sensitivity 79%, precision 34%), the likelihood of developing symptoms consistent with a viral infection three days before symptom onset. The model correctly predicts, almost all of the time (97%), individuals who will not develop viral-like illness symptoms in the next three days. Conversely, the model correctly predicts as positive 34% of the time, individuals who will develop viral-like illness symptoms in the next three days. This model uses a conservative framework, warning potentially pre-symptomatic individuals to socially isolate while minimizing warnings to individuals with a low likelihood of developing viral-like symptoms in the next three days. To our knowledge, this is the first study using wearables and apps with machine learning to predict the occurrence of viral illness-like symptoms. The demonstrated approach to forecasting the onset of viral illness-like symptoms offers a novel, digital decision-making tool for public health safety by potentially limiting viral transmission.

9.
PLoS One ; 16(10): e0258084, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34662346

RESUMO

BACKGROUND: To mitigate the spread of the COVID-19 coronavirus, some countries have adopted more stringent non-pharmaceutical interventions in contrast to those widely used. In addition to standard practices such as enforcing curfews, social distancing, and closure of non-essential service industries, other non-conventional policies also have been implemented, such as the total lockdown of fragmented regions, which are composed of sparsely and highly populated areas. METHODS: In this paper, we model the movement of a host population using a mechanistic approach based on random walks, which are either diffusive or super-diffusive. Infections are realised through a contact process, whereby a susceptible host is infected if in close spatial proximity of the infectious host with an assigned transmission probability. Our focus is on a short-time scale (∼ 3 days), which is the average time lag time before an infected individual becomes infectious. RESULTS: We find that the level of infection remains approximately constant with an increase in population diffusion, and also in the case of faster population dispersal (super-diffusion). Moreover, we demonstrate how the efficacy of imposing a lockdown depends heavily on how susceptible and infectious individuals are distributed over space. CONCLUSION: Our results indicate that on a short-time scale, the type of movement behaviour does not play an important role in rising infection levels. Also, lock-down restrictions are ineffective if the population distribution is homogeneous. However, in the case of a heterogeneous population, lockdowns are effective if a large proportion of infectious carriers are distributed in sparsely populated sub-regions.

10.
Brain Struct Funct ; 2021 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-34687354

RESUMO

Establishing spatial correspondence between subject and template images is necessary in neuroimaging research and clinical applications such as brain mapping and stereotactic neurosurgery. Our anatomical fiducial (AFID) framework has recently been validated to serve as a quantitative measure of image registration based on salient anatomical features. In this study, we sought to apply the AFIDs protocol to the clinic, focusing on structural magnetic resonance images obtained from patients with Parkinson's disease (PD). We confirmed AFIDs could be placed to millimetric accuracy in the PD dataset with results comparable to those in normal control subjects. We evaluated subject-to-template registration using this framework by aligning the clinical scans to standard template space using a robust open preprocessing workflow. We found that registration errors measured using AFIDs were higher than previously reported, suggesting the need for optimization of image processing pipelines for clinical grade datasets. Finally, we examined the utility of using point-to-point distances between AFIDs as a morphometric biomarker of PD, finding evidence of reduced distances between AFIDs that circumscribe regions known to be affected in PD including the substantia nigra. Overall, we provide evidence that AFIDs can be successfully applied in a clinical setting and utilized to provide localized and quantitative measures of registration error. AFIDs provide clinicians and researchers with a common, open framework for quality control and validation of spatial correspondence and the location of anatomical structures, facilitating aggregation of imaging datasets and comparisons between various neurological conditions.

11.
Braz. j. biol ; 81(3): 601-610, July-Sept. 2021. tab, graf
Artigo em Inglês | LILACS-Express | LILACS | ID: biblio-1153382

RESUMO

Abstract The present study aimed to assess population structure and phylogenetic relationships of nine subspecies of Brassica rapa L. represented with thirty-five accessions cover a wide range of species distribution area using isozyme analysis in order to select more diverse accessions as supplementary resources that can be utilized for improvement of B. napus. Enzyme analysis resulted in detecting 14 putative polymorphic loci with 27 alleles. Mean allele frequency 0.04 (rare alleles) was observed in Cat4A and Cat4B in sub species Oleifera accession CR 2204/79 and in subspecies trilocularis accessions CR 2215/88 and CR 2244/88. The highest genetic diversity measures were observed in subspecies dichotoma, accession CR 1585/96 (the highest average of observed (H0) and expected heterozygosity (He), and number of alleles per locus (Ae)). These observations make this accession valuable genetic resource to be included in breeding programs for the improvement of oilseed B. napus. The average fixation index (F) is significantly higher than zero for the analysis accessions indicating a significant deficiency of heteozygosity. The divergence among subspecies indicated very great genetic differentiation (FST = 0.8972) which means that about 90% of genetic diversity is distributed among subspecies, while 10% of the diversity is distributed within subspecies. This coincides with low value of gene flow (Nm = 0.0287). B. rapa ssp. oleifera (turnip rape) and B. rapa ssp. trilocularis (sarson) were grouped under one cluster which coincides with the morphological classification.


Resumo O presente estudo teve como objetivo avaliar a estrutura populacional e as relações filogenéticas de nove subespécies de Brassica rapa L. representadas com 35 acessos, cobrindo uma ampla gama de áreas de distribuição de espécies usando análise isoenzimática, a fim de selecionar acessos mais diversos como recursos suplementares que podem ser utilizados para melhoria de B. napus. A análise enzimática resultou na detecção de 14 loci polimórficos putativos com 27 alelos. A frequência média de 0,04 alelo (alelos raros) foi observada em Cat4A e Cat4B, nas subespécies Oleifera CR 2204/79 e nas subespécies trilocularis CR 2215/88 e CR 2244/88. As maiores medidas de diversidade genética foram observadas na subespécie dicotômica CR 1585/96 (a média mais alta observada (H0) e heterozigosidade esperada (He) e número de alelos por locus (Ae). Essas observações tornam esse acesso um valioso recurso genético a ser incluído em programas de melhoramento de oleaginosas B. napus. O índice médio de fixação (F) é significativamente maior que 0 para os acessos à análise, indicando uma deficiência significativa de heterozigose. A divergência entre as subespécies indicou uma grande diferenciação genética (FST = 0,8972), o que significa que cerca de 90% da diversidade genética é distribuída entre as subespécies, enquanto 10% da diversidade é distribuída nas subespécies. Isso coincide com o baixo valor do fluxo gênico (Nm = 0,0287). B. rapa ssp. oleifera (nabo) e B. rapa ssp. trilocularis (sarson) foram agrupados conforme a classificação morfológica.

12.
Plast Reconstr Surg Glob Open ; 9(9): e3816, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34549006

RESUMO

Venous flaps are nonphysiologic flaps in which the venous system replaces the vascular circuit found in conventional flaps, serving as inflow as well as outflow. Although a main concern with venous flaps has been their reliability, this can be improved by manipulating their physiology using shunt restriction. The soft, pliable tissue provided by venous flaps coupled with the low donor site morbidity and ease of flap harvest make them ideal for coverage of moderate-sized facial defects, which may be too large for local options yet too small for conventional free flaps. We report the use of a large, 70 cm2 arterialized venous free flap to reconstruct a complex forehead deficit after basal cell carcinoma resection. Furthermore, we present the first report of the successful use of valvulotomes in the case of a large, reverse flow arterialized venous flap where several in-series valves were found to prevent adequate perfusion of the flap. Upon removal of the valves, complete perfusion of the flap was achieved.

13.
Phytopathology ; 2021 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-34579556

RESUMO

Shrub willows (Salix spp.) are emerging as a viable lignocellulosic, second-generation bioenergy crop with many growth characteristics favorable for marginal lands in New York State and surrounding areas. Willow rust, caused by members of the genus Melampsora, is the most limiting disease of shrub willow in this region and remains extremely understudied. In this study, genetic diversity, genetic structure, and pathogen clonality were examined in Melampsora americana over two growing seasons using genotyping-by-sequencing to identify single nucleotide polymorphism markers. In conjunction with this project, a reference genome of rust isolate R15-033-03 was generated to aid in variant discovery. Sampling between years allowed for regional and site-specific investigation into population dynamics, in the context of both wild and cultivated hosts within high density plantings. This work revealed that this pathogen is largely panmictic over the sampled areas with few sites showing moderate genetic differentiation. This data supports the hypothesis of sexual recombination between growing seasons as no genotype persisted across the two years of sampling. Additionally, clonality was determined as a driver of pathogen populations within cultivated fields and single shrubs, however there is also evidence of high genetic diversity of rust isolates in all settings. Together, this work provides a framework for M. americana population structure in the Great Lakes region, providing crucial information that can aid in future resistance breeding efforts.

14.
Artigo em Inglês | MEDLINE | ID: mdl-34516380

RESUMO

Optical coherence tomography (OCT) has been identified as a non-invasive and inexpensive imaging modality to discover potential biomarkers for Alzheimer's diagnosis and progress determination. Current hypotheses presume the thickness of the retinal layers, which are analyzable within OCT scans, as an effective biomarker for the presence of Alzheimer's. As a logical first step, this work concentrates on the accurate segmentation of retinal layers to isolate the layers for further analysis. This paper proposes a generative adversarial network (GAN) that concurrently learns to increase the image resolution for higher clarity and then segment the retinal layers. We propose a multi-stage \& multi-discriminatory generative adversarial network (MultiSDGAN) specifically for superresolution and segmentation of OCT scans of the retinal layer. The resulting generator is adversarially trained against multiple discriminator networks at multiple stages. We aim to avoid early saturation of generator model training leading to poor segmentation accuracies and enhance the process of OCT domain translation by satisfying all the discriminators in multiple scales. We also investigated incorporating the Dice loss and Structured Similarity Index Measure (SSIM) as additional loss functions to specifically target and improve our proposed GAN architecture's segmentation and superresolution performance, respectively. The ablation study results conducted on our data set suggest that the proposed MultiSDGAN with ten-fold cross-validation (10-CV) provides a reduced equal error rate with 44.24% and 34.09% relative improvements, respectively (p-values of the improvement level tests<.01). Furthermore, our experimental results also demonstrate that the addition of the new terms to the loss function improves the segmentation results significantly by relative improvements of 31.33% (p-value<.01).

15.
Front Neurosci ; 15: 716538, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34512250

RESUMO

Coordinate invariance of physical laws is central in physics, it grants us the freedom to express observations in coordinate systems that provide computational convenience. In the context of medical imaging there are numerous examples where departing from Cartesian to curvilinear coordinates leads to ease of visualization and simplicity, such as spherical coordinates in the brain's cortex, or universal ventricular coordinates in the heart. In this work we introduce tools that enhance the use of existing diffusion tractography approaches to utilize arbitrary coordinates. To test our method we perform simulations that gauge tractography performance by calculating the specificity and sensitivity of tracts generated from curvilinear coordinates in comparison with those generated from Cartesian coordinates, and we find that curvilinear coordinates generally show improved sensitivity and specificity compared to Cartesian. Also, as an application of our method, we show how harmonic coordinates can be used to enhance tractography for the hippocampus.

16.
Cancers (Basel) ; 13(18)2021 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-34572873

RESUMO

Despite considerable growth in our understanding of the heterogeneous biology and pathogenesis of acute myeloid leukemia (AML) in recent decades, for nearly forty years, little progress was gained in the realm of novel therapeutics. Since 2017, however, nine agents have been FDA-approved for patients with AML in both the upfront and relapsed/refractory (R/R) settings. Most of these compounds function as inhibitors of key cell cycle enzymatic pathways or mediators of leukemic proliferation and survival. They have been approved both as single agents and in combination with conventional or reduced-intensity conventional chemotherapeutics. In this article, we review the molecular landscape of de novo vs. R/R AML and highlight the potential translational impact of defined molecular disease subsets. We also highlight several recent agents that have entered the therapeutic armamentarium and where they fit in the AML treatment landscape, with a focus on FLT3 inhibitors, IDH1 and IDH2 inhibitors, and venetoclax. Finally, we close with a survey of two promising novel agents under investigation that are poised to enter the mainstream clinical arena in the near future.

17.
Brain Pathol ; : e13017, 2021 Sep 19.
Artigo em Inglês | MEDLINE | ID: mdl-34538024

RESUMO

Periventricular white matter hyperintensities (pvWMH) are neuroimaging abnormalities surrounding the lateral ventricles that are apparent on magnetic resonance imaging (MRI). They are associated with age, neurodegenerative disease, and cerebrovascular risk factors. While pvWMH ultimately represent a loss of white matter structural integrity, the pathological causes are heterogeneous in nature, and currently, cannot be distinguished using neuroimaging alone. pvWMH could occur because of a combination of small vessel disease (SVD), ependymal loss, blood-brain barrier dysfunction, and microgliosis. In this study we aimed to characterize microvascular stenosis, fibrinogen extravasation, and microgliosis within pvWMH with and without imaging evidence of periventricular infarction. Using postmortem neuroimaging of human brains (n = 20), we identified pvWMH with and without periventricular infarcts (PVI). We performed histological analysis of microvessel stenosis, perivascular spaces, microgliosis, and immunohistochemistry against fibrinogen as a measure of serum protein extravasation. Herein, we report distinctions between pvWMH with and without periventricular infarcts based on associations with microvessel stenosis, enlarged perivascular spaces, and fibrinogen IHC. Microvessel stenosis was significantly associated with PVI and with cellular deposition of fibrinogen in the white matter. The presence of fibrinogen was associated with PVI and increased number of microglia. These findings suggest that neuroimaging-based detection of infarction within pvWMH may help distinguish more severe lesions, associated with underlying microvascular disease and BBB dysfunction, from milder pvWMH that are a highly frequent finding on MRI.

18.
Braz J Biol ; 83: e250179, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34524376

RESUMO

Diabetes mellitus (DM) is a non-communicable disease throughout the world in which there is persistently high blood glucose level from the normal range. The diabetes and insulin resistance are mainly responsible for the morbidities and mortalities of humans in the world. This disease is mainly regulated by various enzymes and hormones among which Glycogen synthase kinase-3 (GSK-3) is a principle enzyme and insulin is the key hormone regulating it. The GSK-3, that is the key enzyme is normally showing its actions by various mechanisms that include its phosphorylation, formation of protein complexes, and other cellular distribution and thus it control and directly affects cellular morphology, its growth, mobility and apoptosis of the cell. Disturbances in the action of GSK-3 enzyme may leads to various disease conditions that include insulin resistance leading to diabetes, neurological disease like Alzheimer's disease and cancer. Fluoroquinolones are the most common class of drugs that shows dysglycemic effects via interacting with GSK-3 enzyme. Therefore, it is the need of the day to properly understand functions and mechanisms of GSK-3, especially its role in glucose homeostasis via effects on glycogen synthase.


Assuntos
Diabetes Mellitus , Resistência à Insulina , Glucose , Quinase 3 da Glicogênio Sintase , Homeostase , Humanos
20.
Artigo em Inglês | MEDLINE | ID: mdl-34400345

RESUMO

OBJECTIVES: To analyse nosocomial transmission in the early stages of the coronavirus 2019 (COVID-19) pandemic at a large multisite healthcare institution. Nosocomial incidence is linked with infection control interventions. METHODS: Viral genome sequence and epidemiological data were analysed for 574 consecutive patients, including 86 nosocomial cases, with a positive PCR test for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) during the first 19 days of the pandemic. RESULTS: Forty-four putative transmission clusters were found through epidemiological analysis; these included 234 cases and all 86 nosocomial cases. SARS-CoV-2 genome sequences were obtained from 168/234 (72%) of these cases in epidemiological clusters, including 77/86 nosocomial cases (90%). Only 75/168 (45%) of epidemiologically linked, sequenced cases were not refuted by applying genomic data, creating 14 final clusters accounting for 59/77 sequenced nosocomial cases (77%). Viral haplotypes from these clusters were enriched 1-14x (median 4x) compared to the community. Three factors implicated unidentified cases in transmission: (a) community-onset or indeterminate cases were absent in 7/14 clusters (50%), (b) four clusters (29%) had additional evidence of cryptic transmission, and (c) in three clusters (21%) diagnosis of the earliest case was delayed, which may have facilitated transmission. Nosocomial cases decreased to low levels (0-2 per day) despite continuing high numbers of admissions of community-onset SARS-CoV-2 cases (40-50 per day) and before the impact of introducing universal face masks and banning hospital visitors. CONCLUSION: Genomics was necessary to accurately resolve transmission clusters. Our data support unidentified cases-such as healthcare workers or asymptomatic patients-as important vectors of transmission. Evidence is needed to ascertain whether routine screening increases case ascertainment and limits nosocomial transmission.

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