tbuckley/cabot-search huggingface dataset:
Above and beyond the concrete: The diverse representational substrates of the predictive brain
Authors: Michael Gilead, Yaacov Trope, Nira Liberman
Journal: Behavioral and Brain Sciences (2019)

Abstract In recent years, scientists have increasingly taken to investigate the predictive nature of cognition. We argue that prediction relies on abstraction, and thus theories of predictive cognition need an explicit theory of abstract representation. We propose such a theory of the abstract representational capacities that allow humans to transcend the “here-and-now.” Consistent with the predictive cognition literature, we suggest that the representational substrates of the mind are built as a hierarchy , ranging from the concrete to the abstract; however, we argue that there are qualitative differences between elements along this hierarchy, generating meaningful, often unacknowledged, diversity. Echoing views from philosophy, we suggest that the representational hierarchy can be parsed into: modality-specific representations, instantiated on perceptual similarity; multimodal representations, instantiated primarily on the discovery of spatiotemporal contiguity; and categorical representations, instantiated primarily on social interaction. These elements serve as the building blocks of complex structure s discussed in cognitive psychology (e.g., episodes, scripts) and are the inputs for mental representations that behave like functions, typically discussed in linguistics (i.e., predicators ). We support our argument for representational diversity by explaining how the elements in our ontology are all required to account for humans’ predictive cognition (e.g., in subserving logic-based prediction; in optimizing the trade-off between accurate and detailed predictions) and by examining how the neuroscientific evidence coheres with our account. In doing so, we provide a testable model of the neural bases of conceptual cognition and highlight several important implications to research on self-projection, reinforcement learning, and predictive-processing models of psychopathology.
Intelligent gold nanostars for <i>in vivo</i> CT imaging and catalase-enhanced synergistic photodynamic &amp; photothermal tumor therapy
Authors: Lin Zhang, Xiao-Quan Yang, Jian-Shuang Wei, Xing Li, Huan Wang, Yuan-Di Zhao
Journal: Theranostics (2019)

Photodynamic therapy (PDT) is a clinically approved and minimally invasive form of cancer treatment. However, due to hypoxia at the tumor site and phototoxicity to normal tissues, monotherapies using photosensitizers remain suboptimal. This study aimed to develop a highly selective controlled catalase-enhanced synergistic photodynamic and photothermal cancer therapy based on gold nanostars. Methods: Gold nanostars (GNS) with high thermal conversion efficiency were used as the core for photothermal therapy (PTT) and the shell consisted of the photosensitizer Ce6-loaded mesoporous silicon. The shell was modified with catalase (E), which catalyzes the conversion of hydrogen peroxide to oxygen at the tumor site, alleviating hypoxia and increasing the effect of the photodynamic treatment. Finally, a phospholipid derivative with c(RGDyK) was used as the targeting moiety and the nanoparticle-encapsulating material. Results: The nanoprobe exhibited good dispersion, high stability, and high photothermal conversion efficiency (~28%) for PTT as well as a photodynamic "on-off" effect on Ce6 encapsulated in mesoporous channels. The "release" of Ce6 was only triggered under photothermal stimulation in vivo. Due to its targeting ability, 72 h after injection of the probe, the tumor site in mice showed an observable CT response. The combined treatment using photothermal therapy (PTT) and catalase-enhanced photo-controlled PDT exerted a superior effect to PTT or PDT monotherapies. Conclusion: Our findings demonstrate that the use of this intelligent nanoprobe for CT-targeted image-guided treatment of tumors with integrated photothermal therapy (PTT) and catalase-enhanced controlled photodynamic therapy (PDT) may provide a novel approach for cancer theranostics.
Pre-emptive pangenotypic direct acting antiviral therapy in donor HCV-positive to recipient HCV-negative heart transplantation: an open-label study
Authors: Emily D Bethea, Kerry Gaj, Jenna L Gustafson, Andrea Axtell, Taylor Lebeis, Mark Schoenike, Karen Turvey, Erin Coglianese, Sunu Thomas, Christopher Newton-Cheh, Nasrien Ibrahim, William Carlson, Jennifer E Ho, Ravi Shah, Matthew Nayor, Thais Gift, Sarah Shao, Amanda Dugal, James Markmann, Nahel Elias, Heidi Yeh, Karin Andersson, Daniel Pratt, Irun Bhan, Kassem Safa, Jay Fishman, Camille Kotton, Paul Myoung, Mauricio A Villavicencio, David D'Alessandro, Raymond T Chung, Gregory D Lewis
Journal: The Lancet. Gastroenterology & hepatology (2019)
ERS statement on tracheomalacia and bronchomalacia in children
Authors: Colin Wallis, Efthymia Alexopoulou, Juan L. Antón-Pacheco, Jayesh M. Bhatt, Andrew Bush, Anne B. Chang, Anne-Marie Charatsi, Courtney Coleman, Julie Depiazzi, Konstantinos Douros, Ernst Eber, Mark Everard, Ahmed Kantar, Ian B. Masters, Fabio Midulla, Raffaella Nenna, Derek Roebuck, Deborah Snijders, Kostas Priftis
Journal: European Respiratory Journal (2019)

Tracheomalacia and tracheobronchomalacia may be primary abnormalities of the large airways or associated with a wide variety of congenital and acquired conditions. The evidence on diagnosis, classification and management is scant. There is no universally accepted classification of severity. Clinical presentation includes early-onset stridor or fixed wheeze, recurrent infections, brassy cough and even near-death attacks, depending on the site and severity of the lesion. Diagnosis is usually made by flexible bronchoscopy in a free-breathing child but may also be shown by other dynamic imaging techniques such as low-contrast volume bronchography, computed tomography or magnetic resonance imaging. Lung function testing can provide supportive evidence but is not diagnostic. Management may be medical or surgical, depending on the nature and severity of the lesions, but the evidence base for any therapy is limited. While medical options that include bronchodilators, anti-muscarinic agents, mucolytics and antibiotics (as well as treatment of comorbidities and associated conditions) are used, there is currently little evidence for benefit. Chest physiotherapy is commonly prescribed, but the evidence base is poor. When symptoms are severe, surgical options include aortopexy or posterior tracheopexy, tracheal resection of short affected segments, internal stents and external airway splinting. If respiratory support is needed, continuous positive airway pressure is the most commonly used modality either via a face mask or tracheostomy. Parents of children with tracheobronchomalacia report diagnostic delays and anxieties about how to manage their child's condition, and want more information. There is a need for more research to establish an evidence base for malacia. This European Respiratory Society statement provides a review of the current literature to inform future study.
TOP: Time-to-Event Bayesian Optimal Phase II Trial Design for Cancer Immunotherapy
Authors: Ruitao Lin, Robert L Coleman, Ying Yuan
Journal: JNCI Journal of the National Cancer Institute (2019)

Immunotherapies have revolutionized cancer treatment. Unlike chemotherapies, immune agents often take longer to show benefit, and the complex and unique mechanism of action of these agents renders the use of multiple endpoints more appropriate in some trials. These new features of immunotherapy make conventional phase II trial designs, which assume a single binary endpoint that is quickly ascertainable, inefficient and dysfunctional.We propose a flexible and efficient time-to-event Bayesian optimal phase II (TOP) design. The TOP design is efficient in that it allows real-time "go/no-go" interim decision making in the presence of late-onset responses by using all available data and maximizes statistical power for detecting effective treatments. TOP is flexible in the number of interim looks and capable of handling simple and complicated endpoints under a unified framework. We conduct simulation studies to evaluate the operating characteristics of the TOP design.In the considered trial settings, compared to some existing Bayesian designs, the TOP design shortens the trial duration by 4-10 months and improves the power to detect effective treatment up to 90%, with well-controlled type I errors.The TOP design is transparent and easy to implement, as its decision rules can be tabulated and included in the protocol prior to the conduct of the trial. The TOP design provides a flexible, efficient, and easy-to-implement method to accelerate and improve the development of immunotherapies.
Association Between Plant-Based Dietary Patterns and Risk of Type 2 Diabetes
Authors: Frank Qian, Gang Liu, Frank B. Hu, Shilpa N. Bhupathiraju, Qi Sun
Journal: JAMA Internal Medicine (2019)

Accumulating epidemiologic evidence has suggested favorable associations between plant-based dietary patterns and risk of type 2 diabetes, although there is a lack of a quantitative summary of evidence substantiating this important association.To quantitatively synthesize available prospective observational evidence on the association between plant-based dietary patterns and risk of type 2 diabetes.A systematic search of PubMed and MEDLINE, Embase, Web of Science, and reference lists through February 15, 2019, was conducted. Data analysis was conducted between December 2018 and February 2019.All prospective observational studies that examined the association between adherence to plant-based dietary patterns and incidence of type 2 diabetes among adults 18 years or older were identified.Meta-analysis of Observational Studies in Epidemiology guidelines for data abstraction and reporting were followed, and a National Heart, Lung, and Blood Institute assessment tool was used to evaluate study quality. Two authors independently conducted full-text assessments and data abstraction. Meta-analysis was conducted using the random-effects method to calculate the overall relative risk (RR) and 95% CI.Level of adherence to a plant-based diet and incidence of type 2 diabetes.A total of 9 studies were identified, totaling 307 099 participants with 23 544 cases of incident type 2 diabetes. A significant inverse association was observed between higher adherence to a plant-based dietary pattern and risk of type 2 diabetes (RR, 0.77; 95% CI, 0.71-0.84) in comparison with poorer adherence, with modest heterogeneity across studies (I2 = 44.5%; P = .07 for heterogeneity). Similar findings were obtained when using the fixed-effects model (RR, 0.80; 95% CI, 0.75-0.84). Consistent associations were observed across predefined subgroups. This association was strengthened when healthy plant-based foods, such as fruits, vegetables, whole grains, legumes, and nuts, were included in the definition of plant-based patterns (RR, 0.70; 95% CI, 0.62-0.79). Most studies were deemed to have good quality in terms of dietary assessment, disease outcomes, and statistical adjustment for confounding factors. Using restricted cubic splines, a significant inverse linear dose-response association was identified between plant-based dietary indices and risk of type 2 diabetes.Plant-based dietary patterns, especially when they are enriched with healthful plant-based foods, may be beneficial for the primary prevention of type 2 diabetes.
Posttraumatic Stress Disorder and Cognitive Processing Therapy in Youth
Authors: Kendra B. Ferguson
Journal: JAMA Psychiatry (2019)

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Evaluating cancer treatment access in two community cancer centers in Brazil: When managerial tools turns into bad medicine
Authors: C. F. Pinto, G. B. Deboer, E. S. Marotta, M. Taborda, A. D. Mendes, G. R. Albino, G. L. Santos, L. Altoe, A. Mandolesi, C. F. Turci
Journal: Journal of Clinical Oncology (2006)

16036 Background: Despite great developments in cancer treatment, access to treatment is still an important variable that can affect individual prognosis. Phase II or III adjuvant treatment protocols require inclusion to treatment between four to eighth weeks (28 to 56 days) after the initial procedure. The “lead-time” outside clinical trials can be longer than usually recommended and the meaning of this bias over outcome cannot be measured effectively, but reduce this “gap” is considered appropriate. Methods: Two different public community cancer centers (CCC) were evaluated regarding access to a medical oncologist. Referred patients were included and different referral routines were used. Data was collected only for breast cancer patients submitted to adjuvant (or neoadjuvant) systemic therapy. Data included the date the attending physician referred the patient to the CCC and the date patient effectively went on a consultation with an oncologist. Center A referrals depends on “in Hospital” referral center, where all patients are referred and then scheduled to the “needed” specialist. Center B patients are referred promptly to a medical oncologist, regardless of indication, if, i.e., a surgical evaluation or intervention is needed, the oncologist will reschedule it. Results: 76 breast cancer patients were referred to center A and 60 to center B in 2003. Most patients received an adequate surgical intervention, more than 80% of patients were stage I or II. Median time from referral report to a medical oncologist consultation was ten (10) days in Center B and twenty eight (28) days in Center A. Table 1 show treatment variables. Conclusions: Reasons to an almost three times increase in lead-time to access a medical oncologist can be attributed to bureaucratic and managerial policies developed to grant and regulate access to public practice that, in effect, reduced access, created bottlenecks, increased patient expenditures and, potentially, can reduce the overall outcome. [Table: see text] [Table: see text]
Secular Trends in Pubertal Growth Acceleration in Swedish Boys Born From 1947 to 1996
Authors: Claes Ohlsson, Maria Bygdell, Jimmy Celind, Arvid Sondén, Anders Tidblad, Lars Sävendahl, Jenny M. Kindblom
Journal: JAMA Pediatrics (2019)

A secular trend for earlier menarcheal age has been established in girls but there are few studies of pubertal timing for boys.To determine if there is a secular trend for earlier pubertal timing among boys.For this population-based retrospective cohort study conducted in Gothenburg, Sweden, we collected heights and weights from school health records for boys born consecutively from January 1 and onwards in 1947 and every 5 years from 1951 to 1996 (n = 375 for each birth cohort from 1947-1991, n = 340 for the birth cohort in 1996, and n = 4090 for the total cohort). We estimated age at the peak height velocity (PHV), the maximum growth velocity during puberty, and childhood body mass index (BMI) at age 8 years for all study participants. The data were analyzed during 2018 and 2019. Boys were eligible if they had a complete personal identity number and data to calculate their age at PHV and childhood BMI. Approximately 2.4% of the original study population was excluded because they lacked a personal identity number, and in the remaining study population, 4090 (69%) had sufficient data to calculate childhood BMI and age at PHV.The exposure was birth year and a potential confounding factor was childhood BMI.The outcome was age at PHV.Of the 4090 participants, most were white and the mean (SD) age at PHV was 13.9 (1.1) years. A linear regression model revealed a significant association between year of birth and age at PHV. Age at PHV was 1.5 months earlier for every decade increase in birth year (95% CI, -1.72 to -1.19; P < .001). After adjusting for childhood BMI, age at PHV was 1.2 months earlier per decade increase in birth year (95% CI, -1.41 to -0.89). All analyses were repeated in the subgroup of boys born in Sweden and with parents born in Sweden with similar results, indicating that the secular trend was not explained by demographic changes in the population between 1947 and 1996.We provide evidence of a secular trend for earlier pubertal timing in boys that is partially explained by an increased childhood BMI, but other factors that are unknown contribute.
Diagnostic value of BAL lymphocytosis in patients with indeterminate for usual interstitial pneumonia imaging pattern
Authors: Vasilios Tzilas, Argyrios Tzouvelekis, Evangelos Bouros, Theodoros Karampitsakos, Maria Ntasiou, Mattheos Katsaras, Ulrich Costabel, Athol Wells, Demosthenes Bouros
Journal: European Respiratory Journal (2019)

The introduction of antifibrotic agents to clinical practice and the need to better define patient populations for future clinical trials highlight the importance of accurate diagnosis. The main unmet need lies within the population of patients with fibrotic interstitial lung disease (f-ILD) and indeterminate for usual interstitial pneumonia (UIP) pattern on high-resolution computed tomography (HRCT). The differential diagnosis mainly includes idiopathic pulmonary fibrosis (IPF), nonspecific interstitial pneumonia (NSIP), ILD associated with occult collagen tissue disease and, most notably, chronic hypersensitivity pneumonitis. BALF lymphocytosis is a valuable complementary tool in patients with fibrotic interstitial lung disease (f-ILD) and indeterminate-for-UIP pattern on HRCT <http://bit.ly/2nCTkOh>
Novel tumor markers in non-small cell lung cancer detected both in serology and tissue.
Authors: Saba Radhi, Raed Alalawi, Leonardo Mirandola, Yuefei Yu, Apurva Pandey, Ruth D'Cunha, Charles Saadeh, Diane Duyen Thuy Nguyen, Fred L. Hardwicke, Nicholas C. D'Cunha, Lukman Adeoju Tijani, Marjorie Jenkins, Cynthia A. Jumper, Maurizio Chiriva-Internati, Everardo Cobos
Journal: Journal of Clinical Oncology (2012)

e21105 Background: Cancer testis antigens (CTA) are a class of tumor associated antigens, showing a restricted expression in cancer, a strong immunogenicity and weak expression or absence in normal tissues. CTA are a growing family of proteins involved in signal transduction control. Sp17/AKAP4/PTTG1 have been previously investigated, showing promising results as a target antigens. Our aim was to investigate the expression of Sp17/AKAP4/PTTG1 in lung cancer patients. Methods: We analyzed 2 lung cancer cell lines, one normal bronchus cell line, a panel of normal tissues and patient’s cells by RT-PCR, flow-cytometry, immunocytochemistry (ICC), and immunofluorescence (IF). CTA immunogenicity was investigated by measuring circulating specific antibodies in the sera of lung cancer patients. PCR was performed by 35 amplification cycles. RNA integrity in each sample was checked by amplification of ß-actin. We studied the pattern of expression in patients with NSCLC according to histology, gender, and age. Results: Specimens from 11 patients were examined.CTA, Sp17, AKAP-4 and PTTG-1 are aberrantly expressed in lung cancer cell lines and primary cells from patients by RT-PCR, immunocytochemistry, and flow cytometry. ELISA analyses show the presence of circulating CTA-specific antibodies in the sera of lung cancer patients, indicating the immunogenicity of Sp17, AKAP-4 and PTTG-1. The mean age of patients was 60 years(range 57-76). Fifty eight percent were males(N=7). Seventy two percent (n=8) had adenocarcinoma. Six patients were stage IV at diagnosis. There was no difference in the pattern of expression between gender, stage or histology. Conclusions: We showed that CTA, Sp17, AKAP-4 and PTTG-1 can be detected in both sera and tissue of patients with NSCLC. They are potential therapeutic targets for immunotherapies. These may me useful in determining response to treatment as well as asses possible recurrence.
Temporal updating, temporal reasoning, and the domain of time
Authors: Christoph Hoerl, Teresa McCormack
Journal: Behavioral and Brain Sciences (2019)

Abstract We focus on three main sets of topics emerging from the commentaries on our target article. First, we discuss several types of animal behavior that commentators cite as evidence against our claim that animals are restricted to temporal updating and cannot engage in temporal reasoning. In doing so, we illustrate further how explanations of behavior in terms of temporal updating work. Second, we respond to commentators’ queries about the developmental process through which children acquire a capacity for temporal reasoning and about the relation between our account and accounts drawing similar distinctions in other domains of cognition. Finally, we address some broader theoretical issues arising from the commentaries, concerning in particular the question as to how our account relates to the phenomenology of experience in time, and the question as to whether our dichotomy between temporal reasoning and temporal updating is exhaustive, or whether there might be other forms of cognition or representation related to time not captured by it.
The Effect of Nonreversibility on Inferring Rooted Phylogenies
Authors: Svetlana Cherlin, Sarah E Heaps, Tom M W Nye, Richard J Boys, Tom A Williams, T Martin Embley
Journal: Molecular Biology and Evolution (2017)

Most phylogenetic models assume that the evolutionary process is stationary and reversible. In addition to being biologically improbable, these assumptions also impair inference by generating models under which the likelihood does not depend on the position of the root. Consequently, the root of the tree cannot be inferred as part of the analysis. Yet identifying the root position is a key component of phylogenetic inference because it provides a point of reference for polarizing ancestor-descendant relationships and therefore interpreting the tree. In this paper, we investigate the effect of relaxing the unrealistic reversibility assumption and allowing the position of the root to be another unknown. We propose two hierarchical models that are centered on a reversible model but perturbed to allow nonreversibility. The models differ in the degree of structure imposed on the perturbations. The analysis is performed in the Bayesian framework using Markov chain Monte Carlo methods for which software is provided. We illustrate the performance of the two nonreversible models in analyses of simulated data using two types of topological priors. We then apply the models to a real biological data set, the radiation of polyploid yeasts, for which there is robust biological opinion about the root position. Finally, we apply the models to a second biological alignment for which the rooted tree is controversial: the ribosomal tree of life. We compare the two nonreversible models and conclude that both are useful in inferring the position of the root from real biological data.