Showing papers by "Case Western Reserve University published in 2016"
TL;DR: In this paper, the authors present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macro-autophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes.
Abstract: In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes.
For example, a key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process versus those that measure flux through the autophagy pathway (i.e., the complete process including the amount and rate of cargo sequestered and degraded). In particular, a block in macroautophagy that results in autophagosome accumulation must be differentiated from stimuli that increase autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. It is worth emphasizing here that lysosomal digestion is a stage of autophagy and evaluating its competence is a crucial part of the evaluation of autophagic flux, or complete autophagy.
Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. Along these lines, because of the potential for pleiotropic effects due to blocking autophagy through genetic manipulation, it is imperative to target by gene knockout or RNA interference more than one autophagy-related protein. In addition, some individual Atg proteins, or groups of proteins, are involved in other cellular pathways implying that not all Atg proteins can be used as a specific marker for an autophagic process. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular assays, we hope to encourage technical innovation in the field.
5,187 citations
TL;DR: The Global Burden of Diseases, Injuries, and Risk Factors Study 2015 (GBD 2015) as discussed by the authors was used to estimate the incidence, prevalence, and years lived with disability for diseases and injuries at the global, regional, and national scale over the period of 1990 to 2015.
5,050 citations
TL;DR: The Global Burden of Disease 2015 Study provides a comprehensive assessment of all-cause and cause-specific mortality for 249 causes in 195 countries and territories from 1980 to 2015, finding several countries in sub-Saharan Africa had very large gains in life expectancy, rebounding from an era of exceedingly high loss of life due to HIV/AIDS.
4,804 citations
TL;DR: A mesoporous carbon foam co-doped with nitrogen and phosphorus that has a large surface area and good electrocatalytic properties for both ORR and OER and is tested as an air electrode for primary and rechargeable Zn-air batteries.
Abstract: A co-doped carbon material, methods of making such materials, and electrochemical cells and devices comprising such materials are provided. The co-doped carbon material comprises a mesoporous carbon material doped with nitrogen and phoshporous (NPMC). The present NPMC exhibit catalytic activity for both oxygen reduction reaction and oxygen evolution reaction and may be useful as an electrode in an electrochemical cell and particularly as part of a battery. The present NPMC materials may be used as electrodes in primary zinc-air batteries and in rechargeable zinc-air batteries and many other energy systems.
2,425 citations
Boston University1, Cornell University2, Johns Hopkins University3, University of Miami4, University of California, San Francisco5, Texas A&M Health Science Center College of Medicine6, Centers for Disease Control and Prevention7, University of Washington8, Case Western Reserve University9, University of Pennsylvania10, Denver Health Medical Center11, University of Michigan12, University of California, Davis13, University of California, Los Angeles14, United States Department of Veterans Affairs15, Washington University in St. Louis16, Wake Forest University17, University of Utah18, Memorial Sloan Kettering Cancer Center19
TL;DR: These recommendations address the best approaches for antibiotic stewardship programs to influence the optimal use of antibiotics.
Abstract: Evidence-based guidelines for implementation and measurement of antibiotic stewardship interventions in inpatient populations including long-term care were prepared by a multidisciplinary expert panel of the Infectious Diseases Society of America and the Society for Healthcare Epidemiology of America. The panel included clinicians and investigators representing internal medicine, emergency medicine, microbiology, critical care, surgery, epidemiology, pharmacy, and adult and pediatric infectious diseases specialties. These recommendations address the best approaches for antibiotic stewardship programs to influence the optimal use of antibiotics.
1,969 citations
TL;DR: An efficient Co3 O4 -based OER electrocatalyst is designed by a plasma-engraving strategy, which not only produced higher surface area, but also generated oxygen vacancies on Co 3 O4 surface with more Co(2+) formed to improve the electronic conductivity and create more active defects for OER.
Abstract: Co3O4, which is of mixed valences Co2+ and Co3+, has been extensively investigated as an efficient electrocatalyst for the oxygen evolution reaction (OER). The proper control of Co2+/Co3+ ratio in Co3O4 could lead to modifications on its electronic and thus catalytic properties. Herein, we designed an efficient Co3O4-based OER electrocatalyst by a plasma-engraving strategy, which not only produced higher surface area, but also generated oxygen vacancies on Co3O4 surface with more Co2+ formed. The increased surface area ensures the Co3O4 has more sites for OER, and generated oxygen vacancies on Co3O4 surface improve the electronic conductivity and create more active defects for OER. Compared to pristine Co3O4, the engraved Co3O4 exhibits a much higher current density and a lower onset potential. The specific activity of the plasma-engraved Co3O4 nanosheets (0.055 mA cm−2BET at 1.6 V) is 10 times higher than that of pristine Co3O4, which is contributed by the surface oxygen vacancies.
1,641 citations
University of Sannio1, VU University Amsterdam2, University of São Paulo3, University of California, Santa Cruz4, Harvard University5, Khalifa University6, Columbia University7, University of Texas MD Anderson Cancer Center8, Henry Ford Hospital9, Henry Ford Health System10, Baylor College of Medicine11, Memorial Sloan Kettering Cancer Center12, Emory University13, Ohio State University14, Case Western Reserve University15, University of California, San Francisco16, Princess Margaret Cancer Centre17, Van Andel Institute18, University of Washington19
TL;DR: The complete set of genes associated with 1,122 diffuse grade II-III-IV gliomas were defined from The Cancer Genome Atlas and molecular profiles were used to improve disease classification, identify molecular correlations, and provide insights into the progression from low- to high-grade disease.
1,535 citations
Nicholas J Kassebaum1, Megha Arora1, Ryan M Barber1, Zulfiqar A Bhutta2 +679 more•Institutions (268)
TL;DR: In this paper, the authors used the Global Burden of Diseases, Injuries, and Risk Factors Study 2015 (GBD 2015) for all-cause mortality, cause-specific mortality, and non-fatal disease burden to derive HALE and DALYs by sex for 195 countries and territories from 1990 to 2015.
1,533 citations
Harvard University1, Broad Institute2, Howard Hughes Medical Institute3, University of California, Berkeley4, University of California, Los Angeles5, Chinese Academy of Sciences6, Max Planck Society7, Columbia University8, Massachusetts Institute of Technology9, Cayetano Heredia University10, University of Pennsylvania11, University College London12, University of Bern13, Leiden University14, Nanyang Technological University15, University of Chicago16, Estonian Biocentre17, National University of La Plata18, University of Oxford19, University of Bergen20, Novosibirsk State University21, Moscow Institute of Physics and Technology22, Sofia Medical University23, Armenian National Academy of Sciences24, Wellcome Trust Sanger Institute25, Raja Isteri Pengiran Anak Saleha Hospital26, Case Western Reserve University27, University of Tartu28, Estonian Academy of Sciences29, Stony Brook University30, Illumina31, Gladstone Institutes32, University of Helsinki33, University of Washington34, Bashkir State University35, Jaramogi Oginga Odinga University of Science and Technology36, Pompeu Fabra University37, University of Arizona38, University of Cambridge39, Leidos40, Université de Montréal41, University of Utah42, Altai State University43, Council of Scientific and Industrial Research44
TL;DR: It is demonstrated that indigenous Australians, New Guineans and Andamanese do not derive substantial ancestry from an early dispersal of modern humans; instead, their modern human ancestry is consistent with coming from the same source as that of other non-Africans.
Abstract: Here we report the Simons Genome Diversity Project data set: high quality genomes from 300 individuals from 142 diverse populations. These genomes include at least 5.8 million base pairs that are not present in the human reference genome. Our analysis reveals key features of the landscape of human genome variation, including that the rate of accumulation of mutations has accelerated by about 5% in non-Africans compared to Africans since divergence. We show that the ancestors of some pairs of present-day human populations were substantially separated by 100,000 years ago, well before the archaeologically attested onset of behavioural modernity. We also demonstrate that indigenous Australians, New Guineans and Andamanese do not derive substantial ancestry from an early dispersal of modern humans; instead, their modern human ancestry is consistent with coming from the same source as that of other non-Africans.
1,133 citations
Lars G. Fritsche1, Wilmar Igl2, Jessica N. Cooke Bailey3, Felix Grassmann2 +182 more•Institutions (58)
TL;DR: The results support the hypothesis that rare coding variants can pinpoint causal genes within known genetic loci and illustrate that applying the approach systematically to detect new loci requires extremely large sample sizes.
Abstract: Advanced age-related macular degeneration (AMD) is the leading cause of blindness in the elderly, with limited therapeutic options. Here we report on a study of >12 million variants, including 163,714 directly genotyped, mostly rare, protein-altering variants. Analyzing 16,144 patients and 17,832 controls, we identify 52 independently associated common and rare variants (P < 5 × 10(-8)) distributed across 34 loci. Although wet and dry AMD subtypes exhibit predominantly shared genetics, we identify the first genetic association signal specific to wet AMD, near MMP9 (difference P value = 4.1 × 10(-10)). Very rare coding variants (frequency <0.1%) in CFH, CFI and TIMP3 suggest causal roles for these genes, as does a splice variant in SLC16A8. Our results support the hypothesis that rare coding variants can pinpoint causal genes within known genetic loci and illustrate that applying the approach systematically to detect new loci requires extremely large sample sizes.
1,088 citations
Institute for Health Metrics and Evaluation1, University of Washington2, University College London3, Qatar Foundation4, Mashhad University of Medical Sciences5, Queen Elizabeth Hospital Birmingham6, University of Otago7, University of Melbourne8, Johns Hopkins Bayview Medical Center9, Universiti Sains Malaysia10, Burnet Institute11, George Mason University12, Dartmouth College13, Tehran University of Medical Sciences14, University of Bristol15, University of California, San Diego16, University of Texas Southwestern Medical Center17, Environment Agency18, University of Chicago19, Erasmus University Rotterdam20, Case Western Reserve University21, Cancer Treatment Centers of America22, Bayer23, Tufts Medical Center24, Stanford University25, National Research University – Higher School of Economics26, Centers for Disease Control and Prevention27, Jackson State University28, Wuhan University29, Mansoura University30, Imperial College London31
TL;DR: The enormous health loss attributable to viral hepatitis, and the availability of effective vaccines and treatments, suggests an important opportunity to improve public health.
TL;DR: It is reported that metal-free three-dimensional graphene nanoribbon networks (N-GRW) doped with nitrogen exhibited superb bifunctional electrocatalytic activities for both ORR and OER, with an excellent stability in alkaline electrolytes (for example, KOH).
Abstract: Oxygen reduction reaction (ORR) and oxygen evolution reaction (OER) are critical to renewable energy conversion and storage technologies. Heteroatom-doped carbon nanomaterials have been reported to be efficient metal-free electrocatalysts for ORR in fuel cells for energy conversion, as well as ORR and OER in metal-air batteries for energy storage. We reported that metal-free three-dimensional (3D) graphene nanoribbon networks (N-GRW) doped with nitrogen exhibited superb bifunctional electrocatalytic activities for both ORR and OER, with an excellent stability in alkaline electrolytes (for example, KOH). For the first time, it was experimentally demonstrated that the electron-donating quaternary N sites were responsible for ORR, whereas the electron-withdrawing pyridinic N moieties in N-GRW served as active sites for OER. The unique 3D nanoarchitecture provided a high density of the ORR and OER active sites and facilitated the electrolyte and electron transports. As a result, the as-prepared N-GRW holds great potential as a low-cost, highly efficient air cathode in rechargeable metal-air batteries. Rechargeable zinc-air batteries with the N-GRW air electrode in a two-electrode configuration exhibited an open-circuit voltage of 1.46 V, a specific capacity of 873 mAh g−1, and a peak power density of 65 mW cm−2, which could be continuously charged and discharged with an excellent cycling stability. Our work should open up new avenues for the development of various carbon-based metal-free bifunctional electrocatalysts of practical significance.
TL;DR: Carbon-based metal-free catalysts as discussed by the authors have been widely used as catalysts for materials production, clean energy generation and storage, and many other important industrial processes, but metal-based catalysts suffer from high cost, low selectivity, poor durability, susceptibility to gas poisoning and have a detrimental environmental impact.
Abstract: Metals and metal oxides are widely used as catalysts for materials production, clean energy generation and storage, and many other important industrial processes. However, metal-based catalysts suffer from high cost, low selectivity, poor durability, susceptibility to gas poisoning and have a detrimental environmental impact. In 2009, a new class of catalyst based on earth-abundant carbon materials was discovered as an efficient, low-cost, metal-free alternative to platinum for oxygen reduction in fuel cells. Since then, tremendous progress has been made, and carbon-based metal-free catalysts have been demonstrated to be effective for an increasing number of catalytic processes. This Review provides a critical overview of this rapidly developing field, including the molecular design of efficient carbon-based metal-free catalysts, with special emphasis on heteroatom-doped carbon nanotubes and graphene. We also discuss recent advances in the development of carbon-based metal-free catalysts for clean energy conversion and storage, environmental protection and important industrial production, and outline the key challenges and future opportunities in this exciting field. Reducing or even eliminating the need for precious-metal catalysts is crucial for the commercialization of clean energy technologies and various important industrial processes. Carbon materials have recently been shown to be cost-effective and efficient metal-free catalysts in clean energy generation and storage, environmental protection and chemical production.
Wake Forest University1, Veterans Health Administration2, University of Utah3, Boston University4, Medical University of South Carolina5, Stanford University6, Mayo Clinic7, University of California, San Diego8, Rutgers University9, Tulane University10, National Institutes of Health11, University of Alabama at Birmingham12, Vanderbilt University13, University of Florida14, United States Department of Veterans Affairs15, Medical College of Wisconsin16, Case Western Reserve University17
TL;DR: Among ambulatory adults aged 75 years or older, treating to an SBP target of less than 120 mm Hg compared with an SBp target of more than 140mm Hg resulted in significantly lower rates of fatal and nonfatal major cardiovascular events and death from any cause.
Abstract: Importance The appropriate treatment target for systolic blood pressure (SBP) in older patients with hypertension remains uncertain. Objective To evaluate the effects of intensive ( Design, Setting, and Participants A multicenter, randomized clinical trial of patients aged 75 years or older who participated in the Systolic Blood Pressure Intervention Trial (SPRINT). Recruitment began on October 20, 2010, and follow-up ended on August 20, 2015. Interventions Participants were randomized to an SBP target of less than 120 mm Hg (intensive treatment group, n = 1317) or an SBP target of less than 140 mm Hg (standard treatment group, n = 1319). Main Outcomes and Measures The primary cardiovascular disease outcome was a composite of nonfatal myocardial infarction, acute coronary syndrome not resulting in a myocardial infarction, nonfatal stroke, nonfatal acute decompensated heart failure, and death from cardiovascular causes. All-cause mortality was a secondary outcome. Results Among 2636 participants (mean age, 79.9 years; 37.9% women), 2510 (95.2%) provided complete follow-up data. At a median follow-up of 3.14 years, there was a significantly lower rate of the primary composite outcome (102 events in the intensive treatment group vs 148 events in the standard treatment group; hazard ratio [HR], 0.66 [95% CI, 0.51-0.85]) and all-cause mortality (73 deaths vs 107 deaths, respectively; HR, 0.67 [95% CI, 0.49-0.91]). The overall rate of serious adverse events was not different between treatment groups (48.4% in the intensive treatment group vs 48.3% in the standard treatment group; HR, 0.99 [95% CI, 0.89-1.11]). Absolute rates of hypotension were 2.4% in the intensive treatment group vs 1.4% in the standard treatment group (HR, 1.71 [95% CI, 0.97-3.09]), 3.0% vs 2.4%, respectively, for syncope (HR, 1.23 [95% CI, 0.76-2.00]), 4.0% vs 2.7% for electrolyte abnormalities (HR, 1.51 [95% CI, 0.99-2.33]), 5.5% vs 4.0% for acute kidney injury (HR, 1.41 [95% CI, 0.98-2.04]), and 4.9% vs 5.5% for injurious falls (HR, 0.91 [95% CI, 0.65-1.29]). Conclusions and Relevance Among ambulatory adults aged 75 years or older, treating to an SBP target of less than 120 mm Hg compared with an SBP target of less than 140 mm Hg resulted in significantly lower rates of fatal and nonfatal major cardiovascular events and death from any cause. Trial Registration clinicaltrials.gov Identifier:NCT01206062
Boston Children's Hospital1, Harvard University2, University of Calgary3, University of Manchester4, University of Edinburgh5, University of Alabama at Birmingham6, Rotunda Hospital7, Rutgers University8, Wayne State University9, University of Toronto10, University of Pennsylvania11, Oregon Health & Science University12, Utrecht University13, University of Pittsburgh14, Case Western Reserve University15, University College London16, University of Oslo17, VU University Amsterdam18, University of Groningen19
TL;DR: The group agreed on sets of uniform sampling criteria, placental gross descriptors, pathologic terminologies, and diagnostic criteria for placental lesions, which will assist in international comparability of clinicopathologic and scientific studies and assist in refining the significance of lesions associated with adverse pregnancy and later health outcomes.
Abstract: Context.—The value of placental examination in investigations of adverse pregnancy outcomes may be compromised by sampling and definition differences between laboratories. Objective.—To establish an agreed-upon protocol for sampling the placenta, and for diagnostic criteria for placental lesions. Recommendations would cover reporting placentas in tertiary centers as well as in community hospitals and district general hospitals, and are also relevant to the scientific research community. Data Sources.—Areas of controversy or uncertainty were explored prior to a 1-day meeting where placental and perinatal pathologists, and maternal-fetal medicine specialists discussed available evidence and subsequently reached consensus where possible. Conclusions.—The group agreed on sets of uniform sampling criteria, placental gross descriptors, pathologic terminologies, and diagnostic criteria. The terminology and microscopic descriptions for maternal vascular malperfusion, fetal vascular malperfusion, delayed villous m...
TL;DR: The rate of complete remission was higher with inotuzumab ozogamicin than with standard therapy, and a higher percentage of patients in the inotzumabozogamic in group had results below the threshold for minimal residual disease.
Abstract: BackgroundThe prognosis for adults with relapsed acute lymphoblastic leukemia is poor. We sought to determine whether inotuzumab ozogamicin, an anti-CD22 antibody conjugated to calicheamicin, results in better outcomes in patients with relapsed or refractory acute lymphoblastic leukemia than does standard therapy. MethodsIn this phase 3 trial, we randomly assigned adults with relapsed or refractory acute lymphoblastic leukemia to receive either inotuzumab ozogamicin (inotuzumab ozogamicin group) or standard intensive chemotherapy (standard-therapy group). The primary end points were complete remission (including complete remission with incomplete hematologic recovery) and overall survival. ResultsOf the 326 patients who underwent randomization, the first 218 (109 in each group) were included in the primary intention-to-treat analysis of complete remission. The rate of complete remission was significantly higher in the inotuzumab ozogamicin group than in the standard-therapy group (80.7% [95% confidence in...
TL;DR: This paper investigates concepts through seven unique DP tasks as use cases to elucidate techniques needed to produce comparable, and in many cases, superior to results from the state-of-the-art hand-crafted feature-based classification approaches.
Fox Chase Cancer Center1, University of Utah2, University of Texas MD Anderson Cancer Center3, University of California, San Diego4, University of South Florida5, Brigham and Women's Hospital6, University of Alabama at Birmingham7, Roswell Park Cancer Institute8, Case Western Reserve University9, Ohio State University10, University of Colorado Boulder11, University of Nebraska Medical Center12, Johns Hopkins University13, University of California, San Francisco14, University Of Tennessee System15, City of Hope National Medical Center16, University of Washington17, Duke University18, Northwestern University19, Memorial Sloan Kettering Cancer Center20
TL;DR: This portion of the NCCN Guidelines discusses general principles for the diagnosis, staging, and treatment of STS of the extremities, superficial trunk, or head and neck; outlines treatment recommendations by disease stage; and reviews the evidence to support the guidelines recommendations.
Abstract: Soft tissue sarcomas (STS) are rare solid tumors of mesenchymal cell origin that display a heterogenous mix of clinical and pathologic characteristics. STS can develop from fat, muscle, nerves, blood vessels, and other connective tissues. The evaluation and treatment of patients with STS requires a multidisciplinary team with demonstrated expertise in the management of these tumors. The complete NCCN Guidelines for STS provide recommendations for the diagnosis, evaluation, and treatment of extremity/superficial trunk/head and neck STS, as well as intra-abdominal/retroperitoneal STS, gastrointestinal stromal tumors, desmoid tumors, and rhabdomyosarcoma. This portion of the NCCN Guidelines discusses general principles for the diagnosis, staging, and treatment of STS of the extremities, superficial trunk, or head and neck; outlines treatment recommendations by disease stage; and reviews the evidence to support the guidelines recommendations.
TL;DR: It is shown that standard laboratory mouse husbandry has profound effects on the immune system and that environmental changes produce mice with immune systems closer to those of adult humans, and suggested that restoring physiological microbial exposure in laboratory mice could provide a relevant tool for modelling immunological events in free-living organisms, including humans.
Abstract: Our current understanding of immunology was largely defined in laboratory mice, partly because they are inbred and genetically homogeneous, can be genetically manipulated, allow kinetic tissue analyses to be carried out from the onset of disease, and permit the use of tractable disease models. Comparably reductionist experiments are neither technically nor ethically possible in humans. However, there is growing concern that laboratory mice do not reflect relevant aspects of the human immune system, which may account for failures to translate disease treatments from bench to bedside. Laboratory mice live in abnormally hygienic specific pathogen free (SPF) barrier facilities. Here we show that standard laboratory mouse husbandry has profound effects on the immune system and that environmental changes produce mice with immune systems closer to those of adult humans. Laboratory mice--like newborn, but not adult, humans--lack effector-differentiated and mucosally distributed memory T cells. These cell populations were present in free-living barn populations of feral mice and pet store mice with diverse microbial experience, and were induced in laboratory mice after co-housing with pet store mice, suggesting that the environment is involved in the induction of these cells. Altering the living conditions of mice profoundly affected the cellular composition of the innate and adaptive immune systems, resulted in global changes in blood cell gene expression to patterns that more closely reflected the immune signatures of adult humans rather than neonates, altered resistance to infection, and influenced T-cell differentiation in response to a de novo viral infection. These data highlight the effects of environment on the basal immune state and response to infection and suggest that restoring physiological microbial exposure in laboratory mice could provide a relevant tool for modelling immunological events in free-living organisms, including humans.
TL;DR: The pyrolyzed MPSA/GO acted as the first metal-free bifunctional catalyst with high activities for both oxygen reduction and hydrogen evolution and is a promising bifunctionsal catalyst for renewable energy technologies, particularly regenerative fuel cells.
Abstract: The high cost and scarcity of noble metal catalysts, such as Pt, have hindered the hydrogen production from electrochemical water splitting, the oxygen reduction in fuel cells and batteries. Herein, we developed a simple template-free approach to three-dimensional porous carbon networks codoped with nitrogen and phosphorus by pyrolysis of a supermolecular aggregate of self-assembled melamine, phytic acid, and graphene oxide (MPSA/GO). The pyrolyzed MPSA/GO acted as the first metal-free bifunctional catalyst with high activities for both oxygen reduction and hydrogen evolution. Zn-air batteries with the pyrolyzed MPSA/GO air electrode showed a high peak power density (310 W g(-1) ) and an excellent durability. Thus, the pyrolyzed MPSA/GO is a promising bifunctional catalyst for renewable energy technologies, particularly regenerative fuel cells.
Yasser Iturria-Medina, Roberto C. Sotero1, Paule-Joanne Toussaint, José María Mateos-Pérez +311 more•Institutions (60)
TL;DR: Imaging results suggest that intra-brain vascular dysregulation is an early pathological event during disease development, suggesting early memory deficit associated with the primary disease factors.
Abstract: Multifactorial mechanisms underlying late-onset Alzheimer's disease (LOAD) are poorly characterized from an integrative perspective. Here spatiotemporal alterations in brain amyloid-β deposition, metabolism, vascular, functional activity at rest, structural properties, cognitive integrity and peripheral proteins levels are characterized in relation to LOAD progression. We analyse over 7,700 brain images and tens of plasma and cerebrospinal fluid biomarkers from the Alzheimer's Disease Neuroimaging Initiative (ADNI). Through a multifactorial data-driven analysis, we obtain dynamic LOAD-abnormality indices for all biomarkers, and a tentative temporal ordering of disease progression. Imaging results suggest that intra-brain vascular dysregulation is an early pathological event during disease development. Cognitive decline is noticeable from initial LOAD stages, suggesting early memory deficit associated with the primary disease factors. High abnormality levels are also observed for specific proteins associated with the vascular system's integrity. Although still subjected to the sensitivity of the algorithms and biomarkers employed, our results might contribute to the development of preventive therapeutic interventions.
TL;DR: A Stacked Sparse Autoencoder, an instance of a deep learning strategy, is presented for efficient nuclei detection on high-resolution histopathological images of breast cancer and out-performed nine other state of the art nuclear detection strategies.
Abstract: Automated nuclear detection is a critical step for a number of computer assisted pathology related image analysis algorithms such as for automated grading of breast cancer tissue specimens. The Nottingham Histologic Score system is highly correlated with the shape and appearance of breast cancer nuclei in histopathological images. However, automated nucleus detection is complicated by 1) the large number of nuclei and the size of high resolution digitized pathology images, and 2) the variability in size, shape, appearance, and texture of the individual nuclei. Recently there has been interest in the application of “Deep Learning” strategies for classification and analysis of big image data. Histopathology, given its size and complexity, represents an excellent use case for application of deep learning strategies. In this paper, a Stacked Sparse Autoencoder (SSAE), an instance of a deep learning strategy, is presented for efficient nuclei detection on high-resolution histopathological images of breast cancer. The SSAE learns high-level features from just pixel intensities alone in order to identify distinguishing features of nuclei. A sliding window operation is applied to each image in order to represent image patches via high-level features obtained via the auto-encoder, which are then subsequently fed to a classifier which categorizes each image patch as nuclear or non-nuclear. Across a cohort of 500 histopathological images (2200 $\times$ 2200) and approximately 3500 manually segmented individual nuclei serving as the groundtruth, SSAE was shown to have an improved F-measure 84.49% and an average area under Precision-Recall curve (AveP) 78.83%. The SSAE approach also out-performed nine other state of the art nuclear detection strategies.
TL;DR: In this paper, an advanced bi-functional electrocatalyst for the oxygen reduction reaction (ORR) and oxygen evolution reaction (OER) was designed by simultaneously etching and doping a cobalt sulfides-graphene hybrid with NH3-plasma.
Abstract: Highly efficient electrocatalysts for the oxygen reduction reaction (ORR) and oxygen evolution reaction (OER) have been regarded as the core elements in a wide range of renewable energy technologies. Surface engineering of the electrocatalysts is one of the most popular strategies to improve their catalytic activity. Herein, we, for the first time, designed an advanced bi-functional electrocatalyst for the ORR and OER by simultaneously etching and doping a cobalt sulfides–graphene hybrid with NH3-plasma. The graphene supported Co9S8 nanoparticles were prepared (denoted as Co9S8/G) first, followed by the NH3-plasma treatment, which could not only lead to nitrogen doping into both Co9S8 and graphene, but also partially etch the surface of both Co9S8 and graphene. The heteroatom doping could efficiently tune the electronic properties of Co9S8 and graphene, and the surface etching could expose more active sites for electrocatalysis, which can contribute significantly to the enhanced electrocatalytic performance for ORR and OER. The electrochemical results revealed that the etched and N-doped Co9S8/G shows excellent ORR activity, which is close to that of the commercial Pt/C catalyst, and great OER activity. The strategy developed here provides a novel and efficient approach to prepare hybrid bi-functional electrocatalysts for ORR and OER.
TL;DR: This review discusses developments in computational image analysis tools for predictive modeling of digital pathology images from a detection, segmentation, feature extraction, and tissue classification perspective, and reflects on future opportunities for the quantitation of histopathology.
University of Texas MD Anderson Cancer Center1, Duke University2, University of South Florida3, Northwestern University4, City of Hope National Medical Center5, Fox Chase Cancer Center6, University of California, San Diego7, Seattle Cancer Care Alliance8, Brigham and Women's Hospital9, Memorial Sloan Kettering Cancer Center10, Case Western Reserve University11, University of Utah12, University of Michigan13, Roswell Park Cancer Institute14, Mayo Clinic15, Yale Cancer Center16, Johns Hopkins University17, University of California, San Francisco18, University of Colorado Boulder19, Vanderbilt University20, Washington University in St. Louis21, University of Nebraska Medical Center22, Ohio State University23, Stanford University24, University of Tennessee Health Science Center25, Harvard University26
TL;DR: The recommendations outlined in the NCCN Guidelines for staging, assessment of HER2 overexpression, systemic therapy for locally advanced or metastatic disease, and best supportive care for the prevention and management of symptoms due to advanced disease are discussed.
Abstract: Gastric cancer is the fifth most frequently diagnosed cancer and the third leading cause of death from cancer in the world. Several advances have been made in the staging procedures, imaging techniques, and treatment approaches. The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Gastric Cancer provide an evidence- and consensus-based treatment approach for the management of patients with gastric cancer. This manuscript discusses the recommendations outlined in the NCCN Guidelines for staging, assessment of HER2 overexpression, systemic therapy for locally advanced or metastatic disease, and best supportive care for the prevention and management of symptoms due to advanced disease.
TL;DR: A literature search and prospectively defined study selection sought systematic reviews, meta-analyses, randomized controlled trials, prospective-retrospective studies, and prospective comparative observational studies published from 2006 through 2014 to provide recommendations on appropriate use of breast tumor biomarker assay results to guide decisions on adjuvant systemic therapy for women with early stage invasive breast cancer as mentioned in this paper.
Abstract: PurposeTo provide recommendations on appropriate use of breast tumor biomarker assay results to guide decisions on adjuvant systemic therapy for women with early-stage invasive breast cancer.MethodsA literature search and prospectively defined study selection sought systematic reviews, meta-analyses, randomized controlled trials, prospective-retrospective studies, and prospective comparative observational studies published from 2006 through 2014. Outcomes of interest included overall survival and disease-free or recurrence-free survival. Expert panel members used informal consensus to develop evidence-based guideline recommendations.ResultsThe literature search identified 50 relevant studies. One randomized clinical trial and 18 prospective-retrospective studies were found to have evaluated the clinical utility, as defined by the guideline, of specific biomarkers for guiding decisions on the need for adjuvant systemic therapy. No studies that met guideline criteria for clinical utility were found to guide...
Nicholas J Kassebaum1, Ryan M Barber1, Zulfiqar A Bhutta2, Zulfiqar A Bhutta3 +613 more•Institutions (272)
TL;DR: In this article, the authors quantified maternal mortality throughout the world by underlying cause and age from 1990 to 2015 for ages 10-54 years by systematically compiling and processing all available data sources from 186 of 195 countries and territories.
TL;DR: In this paper, the authors provide an overview of carbon-based catalysts in terms of synthesis, structure/morphology, and catalytic activity and durability enhancement for ORR and OER.
TL;DR: Given its high rate of antibiotic resistance and abysmal outcomes (up to 70% mortality rate from infections caused by XDR strains in some case series), new preventative and therapeutic options for Acinetobacter spp.
Abstract: Acinetobacter is a complex genus, and historically, there has been confusion about the existence of multiple species. The species commonly cause nosocomial infections, predominantly aspiration pneumonia and catheter-associated bacteremia, but can also cause soft tissue and urinary tract infections. Community-acquired infections by Acinetobacter spp. are increasingly reported. Transmission of Acinetobacter and subsequent disease is facilitated by the organism's environmental tenacity, resistance to desiccation, and evasion of host immunity. The virulence properties demonstrated by Acinetobacter spp. primarily stem from evasion of rapid clearance by the innate immune system, effectively enabling high bacterial density that triggers lipopolysaccharide (LPS)-Toll-like receptor 4 (TLR4)-mediated sepsis. Capsular polysaccharide is a critical virulence factor that enables immune evasion, while LPS triggers septic shock. However, the primary driver of clinical outcome is antibiotic resistance. Administration of initially effective therapy is key to improving survival, reducing 30-day mortality threefold. Regrettably, due to the high frequency of this organism having an extreme drug resistance (XDR) phenotype, early initiation of effective therapy is a major clinical challenge. Given its high rate of antibiotic resistance and abysmal outcomes (up to 70% mortality rate from infections caused by XDR strains in some case series), new preventative and therapeutic options for Acinetobacter spp. are desperately needed.
TL;DR: The whole blood tuberculosis risk signature prospectively identified people at risk of developing active tuberculosis, opening the possibility for targeted intervention to prevent the disease.