bluuebunny/crossref_metadata_2025 huggingface dataset:
Fifteen-minute consultation: How to use an interpreter in a medical consultation
Authors: Sarfraz Sofia , Wacogne Ian D
Published: November 2018

The use of interpreters is essential in our multicultural society. The families and patients we treat come from differing backgrounds, cultures and spoken language. Many are not proficient in, or may even entirely lack, the ability to communicate effectively in English. As health professionals, we must meet their needs and manage the risks to provision of good quality care that language barriers may introduce. Use of an interpreter or interpreting service is an important skill, which is rarely formally taught in undergraduate or postgraduate curricula. Here, we present some of the pitfalls of using an interpreter, and offer some tips on getting the best out of their use.
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

Objective

The 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.

Methods

Data 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.

Results

Five 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.

Conclusions

We 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.
CO2 involved synthesis of quinazoline-2,4(1H,3H)-diones in water using melamine as a thermoregulated catalyst
Authors: Zhao Guo-Ying , Mu Ling-Ling , Ullah Latif , Wang Meng , Li Hong-Ping , Guan Xin-Xin
Published: November 2018

In this study, pharmaceutically relevant quinazoline-2,4(1H,3H)-diones were synthesized eco-efficiently by cycloaddition of CO2 and 2-aminobenzonitrile in water, catalyzed by melamine as a thermoregulated catalyst. Quinazoline-2,4(1H,3H)-dione was produced selectively with 92% yield at 120 °C, 4.2 MPa, and automatically separated from the hot catalytic aqueous solution, which was reused directly for several runs until its activity decreased in an obvious manner. Then, the catalyst melamine was recrystallized from the spent aqueous solution via simple cooling and reused for another several catalytic runs. The efficient valorization of CO2 and the straightforward stepwise recovery of the products and catalyst were important to save energy and minimize process waste for the practical industrial production.
A laboratory method for the visualization and quantification of hyporheic flow paths and velocities
Authors: Fruetel Christopher , Mumford Kevin G. , Ferreira da Silva Ana Maria , Rey Alexander , Bascom Kerri S.
Published: November 2018

Hyporheic flow, the flow of water through the permeable material immediately surrounding a river, is important for nutrient cycling, dissolved oxygen transport, and contaminant transport. In addition, there is recent concern regarding the role of hyporheic flow on the contamination of rivers following oil spills. To better understand hyporheic flow paths and velocities, it is important to measure hyporheic flow at high spatial and temporal resolution. A practical method to measure hyporheic flow in a laboratory flume based on dye injection, digital images, and moment analysis was developed. An experiment conducted using a single gravel bar demonstrated good agreement between observations and estimates based on image processing. The measured hyporheic flow field showed upstream and downstream flow that discharged downstream of the bar top, the presence of a flow divide and flow stagnation, and hyporheic flow velocities indicative of turbulent flow for which Darcy’s law is not applicable.
Forest edge-induced damage of cephalo- and cyanolichens in northern temperate rainforests of British Columbia
Authors: Gauslaa Yngvar , Bartemucci Paula , Solhaug Knut Asbjørn
Published: November 2018

Retention of trees after logging is a method of preserving epiphytic lichens; however, epiphytes’ responses to logging disturbance are insufficiently known. We aimed to characterize four viability measures — effective PSII yield (ΦPSII; a proxy for photosynthesis), maximal photosystem II efficiency (FV/FM; a proxy for photoinhibition), chlorophyll a content, and chlorophyll a/b ratio — and the functional parameter specific thallus mass (STM; a proxy for water storage) in sympatric populations of two old-growth lichens (Lobaria retigera (Bory) Trevisan and Lobaria oregana (Tuck.) Müll. Arg.) and the less old-growth dependent Lobaria pulmonaria (L.) Hoffm. along recently logged forest edge gradients within retained forest patches. All species experienced substantially reduced chlorophyll contents near edges, whereas ΦPSII was lower in the two old-growth lichens than in L. pulmonaria. STM, and thus lichen water storage, did not respond to logging, probably because chlorophyll degradation reduced the carbon gain required for necessary acclimation. Reported edge effects on lichen viability were so strong that most of the epiphytic lichens in the retained forest patches were affected. Measured viability variables improved linearly with distances up to ≈120 m from the edge. To avoid logging-induced adverse impacts on the threatened epiphytic lichens of these old-growth rainforests, there is a need to retain forest patches wider than 240 m.
A Simple WiMAX and RFID Band-Notched UWB Bandpass Filter and Its Susceptibility Study
Authors: Murmu Lakhindar , Koley Santasri , Bage Amit , Das Sushrut
Published: November 2018

An ultra-wideband (UWB) bandpass filter (BPF) with a fractional bandwidth (FBW) of about 110%, transmission zero at the high-frequency edge, and band notches at the worldwide interoperability for microwave access (WiMAX) and radio frequency identification (RFID) band is presented in this paper. The filter is based on single short-circuited stub, U-shaped defected ground structure (DGS) array, two U-shaped resonators and two stepped impedance resonators (SIRs). The filter is compact and exhibits a selective filtering characteristic equivalent to a three-pole Chebyshev filter. The design procedure has been described and verified by full-wave electromagnetic (EM) simulation and measurement. The proposed filter has low insertion loss, sharp rejection, and excellent in and out band performance. Due to its applications in WiMAX and RFID systems, the filter may be subjected to high EM radiation from the antenna and nearby sources. Therefore, susceptibility study of such a filter is very important. Hence, the susceptibility study of the band-notched UWB BPF has been carried out by subjecting the structure to an interference source.
Carpal Tunnel Syndrome and Flexor Tendon Rupture in the Wrist with Asymptomatic Scapholunate Advanced Collapse: A Case Report
Authors: Kamihata Satoshi , Oda Takashi , Wada Takuro
Published: November 2018

We experienced a rare case of carpal tunnel syndrome and rupture of the flexor digitorum profundus tendon to the index finger with a scapholunate advanced collapse wrist. We speculated that the lunate that had extruded into the carpal tunnel compressed the median nerve and caused wear of the flexor tendon following neglected perilunate subluxation. Carpal tunnel release, opponensplasty by palmaris longus tendon transfer, and a bridge graft by a half-slip of the flexor carpi radialis tendon resulted in recovery of pinch function and improvement in numbness of the hand.
Persisting Complaints after Carpal Tunnel Release: Nerve Compression by the Palmaris Profundus Muscle
Authors: Poelaert Filip , Van Geluwe Filiep , Van Holder Carlo
Published: November 2018

We present the case of a 66-year-old man who had persisting complaints after initial classical open carpal tunnel release. During revision a reversed palmaris profundus muscle was identified as being the cause of residual compression of the median nerve. Neurolysis with release of the palmaris profundus muscle was performed without resection of this anatomical variant and resulted in full resolution of the complaints.
Endoscopic Excision of Ganglion at Anterolateral Elbow: A Case Report
Authors: Lui Tun Hing
Published: November 2018

Ganglion of the anterolateral elbow is rare and may be associated with compression neuropathy of the radial nerve or its branches. Open ganglionectomy implies extensive soft tissue dissection. We present a case of anterolateral elbow ganglion without any compression neuropathy. This was successfully treated with endoscopic ganglionectomy.
What makes skeletal muscle striated? Discoveries in the endosarcomeric and exosarcomeric cytoskeleton
Authors: Rall Jack A.
Published: November 2018

One of the most iconic images in biology is the cross-striated appearance of a skeletal muscle fiber. The repeating band pattern shows that all of the sarcomeres are the same length. All of the A bands are the same length and are located in the middle of the sarcomeres. Furthermore, all of the myofibrils are transversely aligned across the muscle fiber. It has been known for 300 yr that skeletal muscle is striated, but only in the last 40 yr has a molecular understanding of the striations emerged. In the 1950s it was discovered that the extraction of myosin from myofibrils abolished the A bands, and the myofibrils were no longer striated. With the further extraction of actin, only the Z disks remained. Strangely, the sarcomere length did not change, and these “ghost” myofibrils still exhibited elastic behavior. The breakthrough came in the 1970s with the discovery of the gigantic protein titin. Titin, an elastic protein ~1 µm in length, runs from the Z disk to the middle of the A band and ensures that each sarcomere is the same length. Titin anchors the A band in the middle of the sarcomere and may determine thick-filament length and thus A-band length. In the 1970s it was proposed that the intermediate filament desmin, which surrounds the Z disks, connects adjacent myofibrils, resulting in the striated appearance of a skeletal muscle fiber.
Stability Evaluation of Fault Diagnosis Model Based on Elliptic Fourier Descriptor
Authors: Hu YanZhu , Hu Yu , Ai XinBo , Zhao HuiYang , Meng Zhen , Tian WenJia , Wang Jiao
Published: November 2018

The performance evaluation of fault diagnosis algorithm is an indispensable link in the development and acceptance of the fault diagnosis system. Aiming at the stability evaluation of the fault diagnosis model based on the characteristic clustering, an image edge detection method based on the Elliptic Fourier Descriptor (EFDSE) is proposed to evaluate the stability of the fault diagnosis model, which applies similarity measurement of image to effective evaluation of faulty diagnosis algorithm. The quantitative evaluation index of the diagnostic capability of characterization based cluster fault diagnosis model is used to provide reference for the acceptance and reliability of the diagnosis results. Finally, the effectiveness of the stability evaluation is verified by the fault data of the motor bearings.
Composition Analysis and Feature Selection of the Oral Microbiota Associated with Periodontal Disease
Authors: Chen Wen-Pei , Chang Shih-Hao , Tang Chuan-Yi , Liou Ming-Li , Tsai Suh-Jen Jane , Lin Yaw-Ling
Published: November 2018

Periodontitis is an inflammatory disease involving complex interactions between oral microorganisms and the host immune response. Understanding the structure of the microbiota community associated with periodontitis is essential for improving classifications and diagnoses of various types of periodontal diseases and will facilitate clinical decision-making. In this study, we used a 16S rRNA metagenomics approach to investigate and compare the compositions of the microbiota communities from 76 subgingival plagues samples, including 26 from healthy individuals and 50 from patients with periodontitis. Furthermore, we propose a novel feature selection algorithm for selecting features with more information from many variables with a combination of these features and machine learning methods were used to construct prediction models for predicting the health status of patients with periodontal disease. We identified a total of 12 phyla, 124 genera, and 355 species and observed differences between health- and periodontitis-associated bacterial communities at all phylogenetic levels. We discovered that the generaPorphyromonas,Treponema,Tannerella,Filifactor, andAggregatibacterwere more abundant in patients with periodontal disease, whereasStreptococcus,Haemophilus,Capnocytophaga,Gemella,Campylobacter, andGranulicatellawere found at higher levels in healthy controls. Using our feature selection algorithm, random forests performed better in terms of predictive power than other methods and consumed the least amount of computational time.
Predicting Shear Capacity of FRP‐Reinforced Concrete Beams without Stirrups by Artificial Neural Networks, Gene Expression Programming, and Regression Analysis
Authors: Jumaa Ghazi Bahroz , Yousif Ali Ramadhan
Published: November 2018

The shear strength prediction of fiber‐reinforced polymer‐ (FRP‐) reinforced concrete beams is one of the most complicated issues in structural engineering applications. Developing accurate and reliable prediction models is necessary and cost saving. This paper proposes three new prediction models, utilizing artificial neural networks (ANNs) and gene expression programming (GEP), as a recently developed artificial intelligent techniques, and nonlinear regression analysis (NLR) as a conventional technique. For this purpose, a large database including 269 shear test results of FRP‐reinforced concrete members was collected from the literature. The performance of the proposed models is compared with a large number of available codes and previously proposed equations. The comparative statistical analysis confirmed that the ANNs, GEP, and NLR models, in sequence, showed excellent performance, great efficiency, and high level of accuracy over all other existing models. The ANNs model, and to a lower level the GEP model, showed the superiority in accuracy and efficiency, while the NLR model showed that it is simple, rational, and yet accurate. Additionally, the parametric study indicated that the ANNs model defines accurately the interaction of all parameters on shear capacity prediction and have a great ability to predict the actual response of each parameter in spite of its complexity and fluctuation nature.
Evaluation of Tyrosinase Inhibitory, Antioxidant, Antimicrobial, and Antiaging Activities of Magnolia officinalis Extracts after Aspergillus niger Fermentation
Authors: Wu Lichun , Chen Chihyu , Cheng Chiuyu , Dai Hang , Ai Yazhao , Lin Chiahui , Chung Yingchien
Published: November 2018

This study intended to improve physiological characteristics of Magnolia officinalis bark (MOB) extracts by Aspergillus niger fermentation. M. officinalis bark was extracted using distilled water, 95% ethanol, and methanol, and it was then fermented by A. niger. The physiological characteristics of the fermented extracts, namely, tyrosinase inhibitory activity, antioxidant activity, antibacterial activity, and anti-skin-aging activity, were evaluated and compared with those of unfermented extracts. To determine the safety of the fermented extracts, their cytotoxicity was analyzed by measuring the cell viability of CCD-966SK and human epidermal melanocytes (HEMn) after exposure. The fermented methanol extract exhibited the highest antityrosinase activity, total phenolic content, and antioxidant activity. The total phenolic content of the extracts fermented by A. niger was 3.52 times greater than that of the unfermented extracts. The optimal IC50 values for tyrosinase inhibition and 2,2-diphenyl-1-picrylhydrazyl (DPPH) removal by the A. niger-fermented extracts were 30 and 12 μg/mL, respectively. The fermented methanol extracts inhibited skin-aging-related enzymes such as collagenase, elastase, MMP-1, and MMP-2. Compared with the unfermented extracts, the fermented extracts also contained greater antibacterial activity against tested stains including MRSA. These results could be attributed to an increase in the concentration of original active compounds and the biosynthesis of new compounds during fermentation. In cytotoxicity assays, the A. niger-fermented extracts were nontoxic to CCD-966SK cells, even at 500 μg/mL. Hence, in general, methanol-extracted M. officinalis fermented by A. niger for 72 h has the most active antioxidant, skincare, or antiaging compounds for healthy food or cosmetics applications.
Rock Stability Assessment Based on the Chronological Order of the Characteristic Acoustic Emission Phenomena
Authors: Zhang Penghai , Yang Tianhong , Xu Tao , Yu Qinglei , Zhou Jingren , Zhu Wancheng
Published: November 2018

Sudden inelastic deformations in rock are associated with acoustic emission (AE). Therefore, AE monitoring technique can be used to study the fracture processes of rock. In this paper, AE tests were conducted on the granitic gneiss specimens under the uniaxial compressive loading conditions. The temporal changes in AE hit parameters and spatial‐temporal evolution of AE events during the failure process of the granitic gneiss specimens were studied, and several characteristic AE phenomena (i.e., dramatic increase in dominant frequency, AE energy, and hit rate, the AE event with a high energy level, and the through‐going distribution of the AE events with intermediate energy levels) were statistically analyzed before the failure occurred. It was found that the chronological order of the characteristic AE phenomena was relatively certain and correspondingly had a close relationship with the crack development stage. Because of the difference of the stress level at each crack development stage, the stability at different crack development stages is different. Therefore, a rock stability assessment approach was established based on the chronological order of the characteristic AE phenomena, and then the rock stability was assessed using the proposed approach.
Thermoelasticity Coupling Transient Response of Composite‐Material Direction Pipe
Authors: Zhong Jian-lin , Ren Jie , Ma Da-wei
Published: November 2018

Based on the positive scheme method, the thermal load of the jet flow in an inner composite‐material direction pipe is obtained, and the thermoelasticity coupling transient response is investigated. The positive scheme method with second‐order accuracy is extended for solving the axisymmetric Euler equations, and the supersonic axisymmetric jet flow over a missile afterbody containing jet exhaust is simulated. The correctness of the development for the positive scheme method is verified. With the developed positive scheme method used to simulate the jet flow in the inner direction pipe, the thermal load is obtained. The thermoelasticity coupling finite element model of the composite‐material direction pipe is established, and the stress response under dynamic pressure, unsteady temperature, and coupling state is obtained. Results show that, at the beginning of engine ignition, the effect of dynamic pressure and temperature field on the coupling stress is basically the same, and after that, the contribution of the temperature field to the coupling stress increases, and the thermal stress is the main factor affecting the strength of the composite‐material direction pipe.
Lycium Barbarum Polysaccharides Improve Retinopathy in Diabetic Sprague‐Dawley Rats
Authors: Yao Qing , Yang Yi , Lu Xiaohong , Zhang Qian , Luo Mingxiu , Li P. Andy , Pan Yan
Published: November 2018

Diabetic retinopathy (DR) has become the most frequent cause of impaired visual acuity and blindness in working‐age population in developed countries. Here we use diabetic rats to clarify the role of Lycium barbarum polysaccharides (LBP) on DR. We treated diabetic rats with LBP (400 mg/kg/d or 200 mg/kg/d) orally for 20 weeks. Electroretinogram (ERGs) and Laser Doppler blood flow were measured to assess the retinal function, routine histology and ultrastructural studies were performed to evaluate the morphological alterations, and immunohistochemistry, western blotting, and RT‐PCR were conducted to detect the protein and mRNA levels of pro‐ and antiangiogenic factors. The results showed that diabetes suppressed the amplitudes of a‐wave, b‐wave, and oscillatory potential in ERG, reduced retinal blood flow, decreased the thickness of the retina, and increased the thickness of basement membrane of the retinal capillary. Furthermore, diabetes increased the mRNA and protein expressions of proangiogenic GFAP and VEGF and suppressed the levels of antiangiogenic PEDG. Treatment with LBP either completely or partially reversed the alterations caused by diabetes. It is concluded that the LBP protects retinal function and morphology in diabetic rats, probably through reinstallation of the balance between proangiogenic and antiangiogenic factors, which reduces neovascularization. LBP could be used as a therapeutic drug for DR.
Effect of Low-Calorie Pumpkin Jams Fortified with Soybean on Diabetic Rats: Study of Chemical and Sensory Properties
Authors: Alsuhaibani Amnah M. A. , Al-Kuraieef Amal N.
Published: November 2018

This research investigated the chemical analysis and sensory evaluation of low-calorie formulated pumpkin jams after storage for six months and the effects of the consumption of low-calorie jams on diabetic rats. Pumpkin jam with sucrose, fructose, stevia, and aspartame sweeteners and soybean was prepared and stored at 10°C for six months. Rats were divided into group 1 (negative control), group 2 (positive diabetic groups), and groups 3, 4, and 5 (diabetic groups treated with 10% sucrose, fructose, and stevia soybean jam, respectively). The results indicated that the contents of protein, fat, ash, and fibre were increased in the low-calorie formulated pumpkin jams. The highest sensory scores were recorded for sucrose and fructose soybean jams and then for stevia soybean jam, while the aspartame soybean jam showed significantly lower scores after storage for 3 and 6 months. Rat groups 4 and 5 showed significant decreases in the glucose level, and liver function enzymes activity showed significant increases in insulin and glycogen levels compared to group 2. Conclusion. Low-calorie pumpkin jams with soybean can be stored for 3 months at 10°C without any change. Stevia pumpkin jam with soybean has antidiabetic effects.
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

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

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

The 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

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
Modern Information Technology for Cancer Research: What’s in IT for Me? An Overview of Technologies and Approaches
Authors: Ahlbrandt Janko , Lablans Martin , Glocker Katrin , Stahl-Toyota Sophia , Maier-Hein Klaus , Maier-Hein Lena , Ückert Frank
Published: November 2018

Information technology (IT) can enhance or change many scenarios in cancer research for the better. In this paper, we introduce several examples, starting with clinical data reuse and collaboration including data sharing in research networks. Key challenges are semantic interoperability and data access (including data privacy). We deal with gathering and analyzing genomic information, where cloud computing, uncertainties and reproducibility challenge researchers. Also, new sources for additional phenotypical data are shown in patient-reported outcome and machine learning in imaging. Last, we focus on therapy assistance, introducing tools used in molecular tumor boards and techniques for computer-assisted surgery. We discuss the need for metadata to aggregate and analyze data sets reliably. We conclude with an outlook towards a learning health care system in oncology, which connects bench and bedside by employing modern IT solutions.
Visual Analogue Scales as a Tool for Initial Assessment of Tinnitus Severity: Psychometric Evaluation in a Clinical Population
Authors: Raj-Koziak Danuta , Gos Elzbieta , Swierniak Weronika , Rajchel Joanna J. , Karpiesz Lucyna , Niedzialek Iwona , Wlodarczyk Elzbieta , Skarzynski Henryk , Skarzynski Piotr H.
Published: November 2018

The aim of this study was to evaluate the psychometric properties of patient-reported visual analogue scale (VAS) ratings. All of the participants (100 Polish-speaking adults) completed a Tinnitus Functional Index (TFI) once and a 4-component VAS twice over a period of 3 days. Spearman’s correlation coefficients between the VAS score and global TFI ranged from ρ = 0.52 for VAS-coping (VAS-C) to ρ = 0.81 for VAS-annoyance (VAS-A). Using the Bland-Altman method, the agreement ranged from 93% for VAS-A to 96% for VAS-distress (VAS-D). Interclass correlation coefficients ranged from 0.67 for VAS-C to 0.90 for VAS-A. The VAS cutoff points representing significant tinnitus severity ranged from 45 points for VAS-C to 66 points for VAS-D. VAS scales are a valid and reliable brief screening tool for obtaining quick information about tinnitus.
Spontaneous Regression of Hodgkin Lymphoma: Case Report and Review of the Literature
Authors: Pasvolsky Oren , Berger Tamar , Bernstine Hanna , Hayman Lucille  , Raanani Pia , Vidal Liat
Published: November 2018

Spontaneous regression of Hodgkin lymphoma (HL) is a rare event. We describe a 32-year-old woman with spontaneous regression of HL and review the literature. The patient presented with cervical lymphadenopathy and was diagnosed with stage IIA classical HL. The patient refused to receive any treatment for her disease. Positron emission tomography/computed tomography carried out 2 years later showed complete regression of the lymphadenopathy, without pathological uptake of fluorodeoxyglucose. At the last follow-up, 3.5 years after the initial presentation, the patient is with no evidence of disease. During workup for the HL, concomitant papillary thyroid carcinoma was diagnosed, for which the patient refused treatment as well. The thyroid malignancy has remained stable throughout the follow-up.
IL-1α- und MMP-9-Konzentration in der Tränenflüssigkeit von Patienten mit aktiver okulärer Rosazea vor und nach Behandlung mit systemischem Azithromycin oder Doxycyclin
Authors: Lam-Franco Lorena , Perfecto-Avalos Yocanxochitl , Patiño-Ramirez Beatriz E. , Rodríguez García Alejandro
Published: November 2018

Ziele: Ziel der vorliegenden Arbeit war es, die Konzentration von IL-1α und MMP-9 in der Tränenflüssigkeit von Patienten mit aktiver okulärer Rosazea vor und nach einer systemischen Behandlung mit Azithromycin oder Doxycyclin zu ermitteln. Methoden: Nach vierwöchiger Therapie mit Azithromycin (500 mg/Tag oral an 3 Tagen pro Woche) oder Doxycyclin (200 mg/Tag oral) wurden Tränenflüssigkeitsproben mittels Multiplex-Enzyme-linked Immunosorbent Assay (ELISA) untersucht. Ergebnisse: Es fand sich ein signifikanter Unterschied bei den IL-1α- (37,9 pg/ml) und den MMP-9-Ausgangskonzentrationen (26,7 ng/ml) in der Tränenflüssigkeit zwischen den Augen mit Rosazea und den Kontrollen (0,001 pg/ml für IL-1α und 0,2 ng/ml für MMP-9) (p < 0,001). IL-1α nahm von 47,0 pg/ml vor der Azithromycin-Behandlung auf 23,5 pg/ml nach der Behandlung ab (p = 0,024), wohingegen nach der Doxycyclin-Therapie kein Rückgang zu beobachten war. Demgegenüber sanken die MMP-9-Ausgangskonzentrationen in der Tränenflüssigkeit (10,28 ng/ml) nach der Behandlung mit Doxycyclin (8,36 pg/ml) (p = 0,054), nicht jedoch nach Azithromycin. Es bestand eine starke klinische Korrelation von erhöhten IL-1α-Ausgangskonzentrationen in der Tränenflüssigkeit zwischen Patienten, die auf die Doxycyclin-Therapie angesprochen hatten, und jenen, die nicht darauf angesprochen hatten (p = 0,043). Patienten, die nicht auf Azithromycin angesprochen hatten, wiesen signifikant höhere Ausgangskonzentrationen von MMP-9 auf als Patienten, die nicht auf Doxycyclin angesprochen hatten (p = 0,040). Schlussfolgerungen: Während die IL-1α-Konzentrationen unter Azithromycin zurückgingen, war dies für die MMP-9-Konzentrationen unter Doxycyclin der Fall. Die Zytokin-Ausgangskonzentrationen in der Tränenflüssigkeit sind bei Patienten mit Antibiotika-Versagen deutlich erhöht, was eine mögliche Bedeutung als therapeutische Biomarker bei dieser Erkrankung vermuten lässt. Übersetzung aus Ophthalmic Res 2018;60:109-114 (DOI: 10.1159/000489092)
O léxico do português sob o olhar de Gaetano Osculati: elementos da fauna e flora
Authors: Schultz Benilde Socreppa
Published: November 2018

O Rio Amazonas e sua imensa bacia hidrográfica ladeada por imponentes florestas, sempre exerceram um fascínio imenso em todos que ouviram falar dele. Desde o seu descobridor Vicente Pinzón, que em 1500 denominou-o de Rio Santa Maria del Mar Dulce, até os dias de hoje, aventureiros, biólogos, cartógrafos, geógrafos, indianistas e muitos outros cientistas percorreram suas águas à procura de informações que pudessem explicar a grandiosidade dessa obra da natureza. O fascínio do Rio-mar atraiu também o viajante italiano Gaetano Osculati, que em 26 de outubro de 1847 começou a sua viagem em canoa pelo Rio Napo, cuja nascente está no Equador, nas proximidades do monte Cotopaxi, e foz no Rio Solimões. Gaetano Osculati, espelhando-se em Orellana, faz o mesmo e ao final da sua viagem de quatro anos, escreve Esplorazioni delle Regioni Equatoriali lungo il Napo ed il fiume delle Amazzoni, publicado em Milão no ano de 1854, o qual utilizamos para recolher o léxico português inserido incidentalmente ou voluntariamente na obra. Ao escrever sobre o que observava, na falta de termos em italiano, o explorador se apropria de novas palavras, transcrevendo-as da maneira como as ouviu. Normalmente, há, nas nomeações existentes no interior da narrativa, uma estreita ligação entre o nomear e o narrar: ao nomear, o narrador concentra na palavra uma série de sinais linguísticos, a sua carga cultural, o seu saber e sua capacidade expressiva. Pretendemos, neste artigo, à luz das teorias de Alves (1990; 2010), Klajn (1972) e Nunes (1996), recolher, registrar e classificar os empréstimos lexicais do português e do tupi, na obra de Gaetano Osculati, com o objetivo de contribuir para o estudo da Lexicologia histórica portuguesa e italiana, em especial recuperar os empréstimos lexicais portugueses utilizados pelo viajante italiano.
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.
CHAUI E O MODELO DA NATUREZA HUMANA NA ÉTICA DE ESPINOSA
Authors: Oliva Luís César Guimarães
Published: November 2018

Este artigo aborda uma das contribuições mais relevantes do livro A Nervura do Real, vol. 2, de Marilena Chaui: sua análise da noção de modelo da natureza humana apresentada no Prefácio da parte iv da Ética de Espinosa. Chaui entende este conceito como uma noção comum, afastando-se tanto dos intérpretes que o veem como uma construção puramente imaginária, quanto daqueles que o veem como um exemplo de racionalidade normativa.
CULTURA POLÍTICA NOVA: MARILENA CHAUI NA SECRETARIA MUNICIPAL DE CULTURA
Authors: Pereira Marinê De Souza
Published: November 2018

Homenagem a Marilena em forma de uma (ainda) breve pesquisa sobre o período em que ela esteve à frente da SMC-SP, tendo como referência, principalmente, os seus próprios textos e relatos a respeito dessa experiência institucional.
SER PARTE E TOMAR PARTE
Authors: Teixeira Ravena Olinda
Published: November 2018

O texto inicia seu trajeto no prefácio do Tratado Teológico Político, passa rapidamente pelos conceitos de liberdade e de felicidade da Ética, cita Que é a literatura? de Jean Paul Sartre para dizer que escrever e falar são maneiras de se engajar [tomar parte] no mundo. E, finalmente, homenageia a professora Marilena Chaui, uma intelectual engajada.
THE METAPHYSICS OF AUGUSTINE AND THE FOUNDATION OF THE CARTESIAN SCIENCE
Authors: Teixeira William De Jesus
Published: November 2018

The aim of this paper is to show to what extent Descartes can be situated within the Augustinian metaphysical tradition and to what extent he has departed from it. To this end, we will argue that Descartes has borrowed his main Meditations’ arguments from Augustine’s philosophy. However, in spite of all factual and textual evidence we will provide against the originality of Descartes’ metaphysical discussions, it will be stressed, on the other hand, that in borrowing not only the cogito argument, but also some general features of his philosophy from Augustine’s works, Descartes intends to frame a metaphysics which will be the ground on his new mechanistic physics. Having this in mind, we will hold that no claim can be put forward against the originality and far-reaching scope of Descartes’ philosophical intentions. Indeed, Descartes’ purpose is to build a new science under a metaphysics, even though this metaphysics is the Augustianian one.
MARILENA CHAUI, PENSADORA CONTEMPORÂNEA DO TEOLÓGICO-POLÍTICO
Authors: Barros Douglas Ferreira
Published: November 2018

o texto avalia a extensão do projeto de Marilena em relação ao tema da teologia política. Pretendemos mostrar que sua análise se estende da investigação interna da obra filosófica de Espinosa e chega à avaliação da atuação de grupos religiosos e sua relação com a mídia e o contexto político brasileiro na contemporaneidade. Pretendemos observar as linhas de força que amparam o projeto de Chauí em relação ao tema e quais são as bases de sua crítica ao teológico político.
CONATUS E DURAÇÃO NA ÉTICA DE ESPINOSA
Authors: Minkovicius Dani Barki
Published: November 2018

O artigo visa desenvolver a noção de duração na Ética de Espinosa, mostrando que seu entendimento passa pela discussão de uma outra noção, central na filosofia de Espinosa, qual seja, a noção de conatus. A partir, então, da análise aqui pretendida – análise essa que passará por um estudo sobre a existência, a essência, a substância e o modo, além da noção de definição – será possível uma compreensão positiva da indefinição, e um esclarecimento, enfim, do que Espinosa entende por duração, bem como por conatus.
SIDNEY E O DIREITO DE RESISTÊNCIA
Authors: Barros Alberto Ribeiro Gomes de
Published: November 2018

A intenção do artigo é examinar a reflexão de Algernon Sidney no que se refere ao direito de resistência do povo contra governos tirânicos. Amplamente discutido por autores das mais diversas vertentes políticas, o direito de resistência ocupou um lugar de destaque no debate jurídico, teológico e político no decorrer dos séculos XVI e XVII. Além dos tradicionais argumentos apresentados por huguenotes franceses, monarcômacos escoceses e defensores da causa parlamentar durante as guerras civis inglesas, a defesa de Sidney do direito do povo de julgar, combater e depor tiranos é feita também com base em princípios republicanos, como o império da lei, o bem comum e, principalmente, a liberdade.
A ONTOLOGIA POLÍTICA DE ESPINOSA NA LEITURA DE ANTONIO NEGRI
Authors: Visentin Stefano
Published: November 2018

O texto busca reconstituir alguns momentos fundamentais da leitura negriana de Espinosa, mostrando como ela se presta a uma releitura da modernidade filosófica bem como abre-se para a reflexão política contemporânea. Por fim, são apontados certos aspectos problemáticos da interpretação de Negri.
O ponto cego: o futuro na obra de Ricardo Piglia
Authors: Felippe Eduardo Ferraz
Published: November 2018

A intenção deste ensaio é analisar a articulação entre futuro, experiência e sentido nos escritos de Ricardo Piglia. A princípio proponho uma leitura intensiva da prosa de ficção Respiração Artificial entendendo como se dá a relação entre experiência e sentido no livro. Em um segundo momento, analiso o tema do futuro em suas mais diversas prosas de ficção e ensaios, especialmente como propõe uma noção de Utopia como crítica ao realismo histórico, por meio da leitura da tradição literária argentina e do pós-modernismo norte-americano, o que reafirma o futuro em aberto como uma marca da historicidade de sua escrita.
Que Brasil existe? Estrangeiros na literatura brasileira.
Authors: Chiarelli Stefania
Published: November 2018

O artigo traça breve panorama de autores que tematizam a imigração na literatura brasileira. Judeus, árabes, japoneses, italianos, alemães e afro-descendentes surgem como vozes dissonantes na teia discursiva da nação. Estabelecendo aproximações e contrastes, o texto busca pensar a relevância do enfoque dessas narrativas, que apresentam ângulo específico sobre a identidade nacional.
Entrevista com Milton Hatoum
Authors: Pinto Julio Pimentel , Iegelski Francine , Chiarelli Stefania
Published: November 2018

Entrevista realizada por Júlio Pimentel Pinto, Francine Iegelski e Stefania Chiarelli.
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.