bluuebunny/crossref_metadata_2025_split huggingface dataset:
Preliminary Study of Hospital Wastewater Treatment with a Submerged Membrane Bioreactor (SMBR): Case Study of Songklanagarind Hospital – Thailand
Authors: Preecha U. , Sridang P. , Wanichapichart P. 
Published: November 2018

The objective of this research was to study hospital wastewater treatment using a submerged membrane bioreactor (SMBR). The lab scale unit of SMBR with a working volume of 20 liters was operated at a hydraulic retention time of 0.416 day and 0.208 day at F/M ratio of 0.18 day–1 and 0.29 day–1. The operating conditions were set up to provide good biological treatment without sludge extraction, and two different permeate flux values were studied. The performance of membrane was studied by monitoring the variation of transmenbrane pressure (TMP) during filtration runs. The efficiency of MBR was investigated according to the daily measurements of pH, dissolved oxygen and temperature. The COD, BOD5, NH4+–N, TKN, color, turbidity, SS and Escherichia coli (E.coli) in influent and effluent were analyzed. Membrane fouling intensity occurred slowly when the system operated with flux at 10 L/h/m2 and 20 L/h/m2, which induced high TMP at the initial period of filtration. The fouling rate was at about 0.3022 mbar/day for the permeation of flux at 10 L /h/m2. The fouling rate still remained at 0.2774 mbar/day for 20 L/h/m2. The results showed the great effect of membrane use for total biomass retention and the removal rate of COD, BOD5 and E.coli were over 90%. The characteristics of sludge in SMBR showed healthy floc formations with good settling. Although the ratio of MLVSS/MLSS was lower than the normal range (about 0.2), it was found that the average values of COD and NH4+–N in permeate were lower than 2–80 mg/L and 0.05–6.755 mg/L while the value of turbidity was also less than 3 NTU.
Ih contributes to increased motoneuron excitability in restless legs syndrome
Authors: Czesnik Dirk , Howells James , Bartl Michael , Veiz Elisabeth , Ketzler Rebecca , Kemmet Olga , Walters Arthur S. , Trenkwalder Claudia , Burke David , Paulus Walter 
Published: November 2018

Key points
Restless legs patients complain about sensory and motor symptoms leading to sleep disturbances. Symptoms include painful sensations, an urge to move and involuntary leg movements.
The responsible mechanisms of restless legs syndrome are still not known, although current studies indicate an increased neuronal network excitability. Reflex studies indicate the involvement of spinal structures. Peripheral mechanisms have not been investigated so far.
In the present study, we provide evidence of increased hyperpolarization‐activated cyclic nucleotide‐gated (HCN) channel‐mediated inward rectification in motor axons. The excitability of sensory axons was not changed.
We conclude that, in restless legs syndrome, an increased HCN current in motoneurons may play a pathophysiological role, such that these channels could represent a valuable target for pharmaceutical intervention.
AbstractRestless legs syndrome is a sensorimotor network disorder. So far, the responsible pathophysiological mechanisms are poorly understood. In the present study, we provide evidence that the excitability of peripheral motoneurons contributes to the pathophysiology of restless legs syndrome. In vivo excitability studies on motor and sensory axons of the median nerve were performed on patients with idiopathic restless legs syndrome (iRLS) who were not currently on treatment. The iRLS patients had greater accommodation in motor but not sensory axons to long‐lasting hyperpolarization compared to age‐matched healthy subjects, indicating greater inward rectification in iRLS. The most reasonable explanation is that hyperpolarization‐activated cyclic nucleotide‐gated (HCN) channels open at less hyperpolarized membrane potentials, a view supported by mathematical modelling. The half‐activation potential for HCN channels (Bq) was the single best parameter that accounted for the difference between normal controls and iRLS data. A 6 mV depolarization of Bq reduced the discrepancy between the normal control model and the iRLS data by 92.1%. Taken together, our results suggest an increase in the excitability of motor units in iRLS that could enhance the likelihood of leg movements. The abnormal axonal properties are consistent with other findings indicating that the peripheral system is part of the network involved in iRLS.
Uncovering the heterogeneity of disease impact in axial spondyloarthritis: bivariate trajectories of disease activity and quality of life
Authors: Imkamp Maike , Lima Passos Valéria , Boonen Annelies , Arends Suzanne , Dougados Maxime , Landewé Robert , Ramiro Sofia , Van den Bosch Filip , van der Heijde Desirée , Wink Freke R , Spoorenberg Anneke , van Tubergen Astrid 
Published: November 2018

ObjectiveThe goal of managing axial spondyloarthritis (axSpA) is to improve and maintain patients’ health-related quality of life (HRQoL), mainly through targeting towards low disease activity. Here, we aim to gain insight into the joint evolution of HRQoL and disease activity by identifying and characterising latent subgroups of patients with longstanding disease displaying similar trajectories throughout 8  years of follow-up.MethodsData from Outcome in Ankylosing Spondylitis (AS) International Study (n=161) and Groningen Leeuwarden AS cohort (n=264) were used. Biennially, HRQoL was assessed by AS Quality of Life (ASQoL) and disease activity by AS Disease Activity Score—C reactive protein (ASDAS-CRP). Bivariate trajectories of these outcomes were estimated by group-based trajectory modelling. Next, trajectories were profiled by comparing the latent groups with respect to baseline factors using analysis of variance and χ² test.ResultsFive bivariate trajectories were distinguished, in which ASQoL and ASDAS-CRP were tightly linked: (t1) low impact of disease; (t2) moderate impact; (t3) high impact with major improvement; (t4) high impact with some improvement; (t5) very high impact. Profiling revealed, for example, that (t1) was characterised by male gender and Human Leucocyte Antigen B27 positivity; (t3) by younger age, shorter symptom duration and biological intake and (t5) by the highest proportion of females.ConclusionsWe identified five bivariate trajectories of HRQoL and disease activity demonstrating a clear mutual relationship. The profiles revealed that both individual-related and disease-related features define the type of disease course in respect to HRQoL and disease activity in axSpA. This may provide clinicians insight into the differences among patients and help in the management of the disease.
PIK3CA Amplification Associates with Aggressive Phenotype but Not Markers of AKT-MTOR Signaling in Endometrial Carcinoma
Authors: Holst Frederik , Werner Henrica M.J. , Mjøs Siv , Hoivik Erling A. , Kusonmano Kanthida , Wik Elisabeth , Berg Anna , Birkeland Even , Gibson William J. , Halle Mari K. , Trovik Jone , Cherniack Andrew D. , Kalland Karl-Henning , Mills Gordon B. , Singer Christian F. , Krakstad Camilla , Beroukhim Rameen , Salvesen Helga B. 
Published: November 2018

Abstract

Purpose:
Amplification of PIK3CA, encoding the PI3K catalytic subunit alpha, is common in uterine corpus endometrial carcinoma (UCEC) and linked to an aggressive phenotype. However, it is unclear whether PIK3CA amplification acts via PI3K activation. We investigated the association between PIK3CA amplification, markers of PI3K activity, and prognosis in a large cohort of UCEC specimens.

Experimental Design:
UCECs from 591 clinically annotated patients including 83 tumors with matching metastasis (n = 188) were analyzed by FISH to determine PIK3CA copy-number status. These data were integrated with mRNA and protein expression and clinicopathologic data. Results were verified in The Cancer Genome Atlas dataset.

Results:
PIK3CA amplifications were associated with disease-specific mortality and with other markers of aggressive disease. PIK3CA amplifications were also associated with other amplifications characteristic of the serous-like somatic copy-number alteration (SCNA)–high subgroup of UCEC. Tumors with PIK3CA amplification also demonstrated an increase in phospho-p70S6K but had decreased levels of activated phospho-AKT1-3 as assessed by Reverse Phase Protein Arrays and an mRNA signature of MTOR inhibition.

Conclusions:
PIK3CA amplification is a strong prognostic marker and a potential marker for the aggressive SCNA-high subgroup of UCEC. Although PIK3CA amplification associates with some surrogate measures of increased PI3K activity, markers for AKT1-3 and MTOR signaling are decreased, suggesting that this signaling is not a predominant pathway to promote cancer growth of aggressive serous-like UCEC. Moreover, these associations may reflect features of the SCNA-high subgroup of UCEC rather than effects of PIK3CA amplification itself.
Advances in HER2-Targeted Therapy: Novel Agents and Opportunities Beyond Breast and Gastric Cancer
Authors: Meric-Bernstam Funda , Johnson Amber M. , Dumbrava Ecaterina E. Ileana , Raghav Kanwal , Balaji Kavitha , Bhatt Michelle , Murthy Rashmi K. , Rodon Jordi , Piha-Paul Sarina A. 
Published: November 2018

Abstract
The introduction of HER2-targeted therapy for breast and gastric patients with ERBB2 (HER2) amplification/overexpression has led to dramatic improvements in oncologic outcomes. In the past 20 years, five HER2-targeted therapies have been FDA approved, with four approved in the past 8 years. HER2-targeted therapy similarly was found to improve outcomes in HER2-positive gastric cancer. Over the past decade, with the introduction of next-generation sequencing into clinical practice, our understanding of HER2 biology has dramatically improved. We have recognized that HER2 amplification is not limited to breast and gastric cancer but is also found in a variety of tumor types such as colon cancer, bladder cancer, and biliary cancer. Furthermore, HER2-targeted therapy has signal of activity in several tumor types. In addition to HER2 amplification and overexpression, there is also increased recognition of activating HER2 mutations and their potential therapeutic relevance. Furthermore, there is a rapidly growing number of new therapeutics targeting HER2 including small-molecule inhibitors, antibody–drug conjugates, and bispecific antibodies. Taken together, an increasing number of patients are likely to benefit from approved and emerging HER2-targeted therapies.
The Clinical Impact of the Genomic Landscape of Mismatch Repair–Deficient Cancers
Authors: Germano Giovanni , Amirouchene-Angelozzi Nabil , Rospo Giuseppe , Bardelli Alberto 
Published: November 2018

AbstractThe mismatch repair (MMR) system which detects and corrects base mismatches and insertions and deletions that occur during DNA synthesis is deregulated in approximately 20% of human cancers. MMR-deficient tumors have peculiar properties, including early-onset metastatic potential but generally favorable prognosis, and remarkable response to immune therapy. The functional basis of these atypical clinical features has recently started to be elucidated. Here, we discuss how the biological and clinical features of MMR-deficient tumors might be traced back to their ability to continuously produce new somatic mutations, leading to increased levels of neoantigens, which in turn stimulate immune surveillance.Significance:Tumors carrying defects in DNA MMR accumulate high levels of mutations, a feature linked to rapid tumor progression and acquisition of drug resistance but also favorable prognosis and response to immune-checkpoint blockade. We discuss how the genomic landscape of MMR-deficient tumors affects their biological and clinical behaviors.
PPT1 Promotes Tumor Growth and Is the Molecular Target of Chloroquine Derivatives in Cancer
Authors: Rebecca Vito W. , Nicastri Michael C. , Fennelly Colin , Chude Cynthia I. , Barber-Rotenberg Julie S. , Ronghe Amruta , McAfee Quentin , McLaughlin Noel P. , Zhang Gao , Goldman Aaron R. , Ojha Rani , Piao Shengfu , Noguera-Ortega Estela , Martorella Alessandra , Alicea Gretchen M. , Lee Jennifer J. , Schuchter Lynn M. , Xu Xiaowei , Herlyn Meenhard , Marmorstein Ronen , Gimotty Phyllis A. , Speicher David W. , Winkler Jeffrey D. , Amaravadi Ravi K. 
Published: November 2018

Abstract

Clinical trials repurposing lysosomotropic chloroquine (CQ) derivatives as autophagy inhibitors in cancer demonstrate encouraging results, but the underlying mechanism of action remains unknown. Here, we report a novel dimeric CQ (DC661) capable of deacidifying the lysosome and inhibiting autophagy significantly better than hydroxychloroquine (HCQ). Using an in situ photoaffinity pulldown strategy, we identified palmitoyl-protein thioesterase 1 (PPT1) as a molecular target shared across monomeric and dimeric CQ derivatives. HCQ and Lys05 also bound to and inhibited PPT1 activity, but only DC661 maintained activity in acidic media. Knockout of PPT1 in cancer cells using CRISPR/Cas9 editing abrogates autophagy modulation and cytotoxicity of CQ derivatives, and results in significant impairment of tumor growth similar to that observed with DC661. Elevated expression of PPT1 in tumors correlates with poor survival in patients in a variety of cancers. Thus, PPT1 represents a new target in cancer that can be inhibited with CQ derivatives.

Significance:
This study identifies PPT1 as the previously unknown lysosomal molecular target of monomeric and dimeric CQ derivatives. Genetic suppression of PPT1 impairs tumor growth, and PPT1 levels are elevated in cancer and associated with poor survival. These findings provide a strong rationale for targeting PPT1 in cancer.
This article is highlighted in the In This Issue feature, p. 151
ESPINOSA E O CONHECIMENTO DO BEM E DO MAL
Authors: Scribano Emanuela 
Published: November 2018

As definições do bem e do mal que abrem a Parte iv da Ética parecem posicionar decididamente Espinosa entre os filósofos que consideraram poder defini-los por meio de proposições suscetíveis de verdade e falsidade, reconduzindo, portanto, à razão a origem destas noções. Por outro lado, a proposição 8 da mesma parte afirma de modo inequívoco que o conhecimento dos valores morais é inteiramente redutível a um estado emocional. Dado este aparente paradoxo, trata-se, então, de analisar se e como podem ser conciliadas as definições de bem e de mal e a proposição 8 da Parte IV. O artigo mostra que a filosofia de Espinosa busca produzir uma mutação dos conhecimentos e, portanto, dos desejos; em última instância, uma mutação da natureza do agente, da qual irá derivar, necessariamente, uma mutação na especificação dos bens e nas ações, porque, mudando a natureza da mente, serão diferentes as coisas que provocam alegria e que serão, desse modo, desejadas. Não por acaso, o supremo bem, o conhecimento de Deus, comporta um componente afetivo: a alegria. Trata-se de mostrar que o componente afetivo é intrínseco ao juízo de valor e, ao mesmo tempo, exprime a natureza do sujeito e motiva a sua ação. Por isso, o homem que usa a razão não poderá senão desejar o que lhe é verdadeiramente útil.
Georges Canguilhem et la construction du domaine de la Santé Collective brésilienne
Authors: Ayres José Ricardo de Carvalho Mesquita 
Published: November 2018

L ́épistémologie historique a joué un rôle remarqué dans le développement de la Santé collective brésilienne. Née comme un mouvement simultanément académique, de recherche de nouvelles bases conceptuelles pour un domaine scientifique engagé dans les causes sociales, et politique, de résistance contre la dictature civile et militaire implantée au Brésil en 1964, le dit Mouvement de réforme sanitaire brésilienne a trouvé dans l ́épistémologie historique française un allié puissant. Cet article cherche à revisiter les principaux traits de cette relation, en se focalisant principalement sur les travaux inauguraux de Sergio Arouca et Cecilia Donnangelo et la théorie du processus de travail dans la Santé, développée au sein du Département de médecine préventive de la Faculté de médecine de l ́Université de São Paulo. La discussion est centrée sur la manière selon laquelle, d ́un côté, les concepts philosophiques de Canguilhem, comme le caractère normatif de la vie et de sa connaissance, la discontinuité qualitative entre les phénomènes normaux et pathologiques, la définition de la santé orientée par la notion de valeur et, d ́un autre côté, la méthodologie historique de Canguilhem, focalisée sur le développement rationnel des concepts comme noyau de la recherche historico-épistémologique, la reconnaissance des influences “externes” sur les développements scientifiques, comme les conditions sociales et technologiques, et le rôle positif attribué aux obstacles, aux défaillances et accidents des progrès scientifiques, ont toutes été cruciaux pour promouvoir l ́articulation entre les intérêts politiques et académiques du Mouvement. Ils sont encore des éléments de défi pour les réflexions historiques et philosophiques de la Santé collective.
Social Conformity Effects on Trust in Simulation-Based Human-Robot Interaction
Authors: Volante William G. , Sosna Janine , Kessler Theresa , Sanders Tracy , Hancock P. A. 
Published: November 2018

Objective: We investigated the co-acting influences of communication and social conformity on trust in human-robot interaction. Background: Previous work has investigated aspects of the robot, the human, and the environment as influential factors in the human-robot relationship. Little work has examined the conjoint effects of social conformity and communication on this relationship. As social conformity and communication have been shown to affect human-human trust, there are a priori reasons to believe that they will play an influential role in human-robot trust also. Method: The experiment examined the influences of social conformity and robot communication on trust. A 2 × 2 (communication × social group) design was implemented with each variable having two levels (communication, no communication; positive social group, negative social group). Results: We created a communication manipulation which we then demonstrated to mediate the trust level between human and robot. However, this influence on trust was overcome by social information in which the subsequent trust level, attributed to the robot, was dominated by expressed social group attitudes to that robot. Conclusion: The results confirm the importance of human social assessments over direct robot communication in setting human-robot trust levels. When social opinions are expressed, observers appear to conform to the trust displayed by the group than relying on their own judgment. Application: In human-robot teams, the perceptions of the group may exert a greater impact than even robot communication. This may be especially important when new human members are introduced into such teams.
CT perfusion and diffusion-weighted MR imaging of pancreatic adenocarcinoma: can we predict tumor grade using functional parameters?
Authors: Kovač Jelena Djokić , Đurić-Stefanović Aleksandra , Dugalić Vladimir , Lazić Ljubica , Stanisavljević Dejana , Galun Danijel , Mašulović Dragan 
Published: November 2018

Background Pancreatic adenocarcinoma is a highly lethal disease even in initially resectable patients. Functional imaging procedures such as diffusion-weighted imaging (DWI) and computed tomography (CT)-perfusion might facilitate preoperative prediction of factors influencing prognosis in patients with pancreatic adenocarcinoma. Purpose To evaluate CT-perfusion and DWI quantitative parameters of pancreatic adenocarcinoma and to assess their correlation with clinicopathological features. Material and Methods Forty-four patients with histopathologically proven pancreatic adenocarcinoma underwent CT-perfusion and DWI for estimating blood volume (BV), blood perfusion (BF), mean transit time (MTT), time to peak (TTP), and apparent diffusion coefficient (ADC) values. The statistical analysis was performed using Wilcoxon matched-pairs test, t-test for independent samples, Spearman’s rank correlation coefficient (rs), and receiver operating characteristic analysis. Results The mean CT-perfusion parameters and ADCs were significantly different in pancreatic adenocarcinoma versus healthy parenchyma. BV (2.66 ± 0.98 mL/100g), BF (17.45 ± 4.06 mL/min/100g), and ADCs (0.91 ± 0.15 × 10−3mm/s2) in high-grade tumors were significantly lower in comparison to low-grade tumors (BV = 5.35 ± 1.36 mL/100g, BF = 28.51 ± 7.73 mL/min/100g, ADC = 1.07 ± 0.21 × 10−3mm/s2). For prediction of high-grade tumors, the sensitivity and specificity were 79.2% and 82.4% for BF and 87.5% and 88.2% for BV, respectively. A significant negative correlation was found between BV and tumor size (rs = −0.445, P = 0.029), MTT and tumor size (rs = −0.330, P = 0.043), BV and M-stage (rs = −0.286, P = 0.049), and ADC and M-stage (rs = −0.274, P = 0.038). Moreover, BF and BV values were significantly associated with ADCs. Conclusion CT-perfusion parameters and ADC values could improve preoperative assessment of pancreatic adenocarcinoma with possibility of tumor grade prediction.
Approach to the Assessment and Management of Adult Patients With Atopic Dermatitis: A Consensus Document
Authors: Gooderham Melinda J. , Hong Chih-ho , Albrecht Lorne , Bissonnette Robert , Dhadwal Gurbir , Gniadecki Robert , Grewal Parbeer , Kirchhof Mark G. , Landells Ian , Lansang Perla , Lynde Chuck W. , Papp Kim A. , Poulin Yves , Sussman Gordon , Turchin Irina , Wiseman Marni , Yeung Jensen 
Published: November 2018

Background: Atopic dermatitis (AD) is a chronic, relapsing, and remitting inflammatory skin disease with complex pathophysiology, primarily driven by type 2 inflammation. Existing guidelines often do not reflect all current therapeutic options and guidance on the practical management of patients with AD is lacking. Objectives: To develop practical, up-to-date guidance on the assessment and management of adult patients with AD. Methods: An expert panel of 17 Canadian experts, including 16 dermatologists and 1 allergist, with extensive clinical experience managing moderate-to-severe AD reviewed the available literature from the past 5 years using a defined list of key search terms. This literature, along with clinical expertise and opinion, was used to draft concise, clinically relevant reviews of the current literature. Based on these reviews, experts developed and voted on recommendations and statements to reflect the practical management of adult patients with AD as a guide for health care providers in Canada and across the globe, using a prespecified agreement cutoff of 75%. Results: Eleven consensus statements were approved by the expert panel and reflected 4 key domains: pathophysiology, assessment, comorbidities, and treatment. Conclusions: These statements aim to provide a framework for the assessment and management of adult patients with AD and to guide health care providers in practically relevant aspects of patient management.