bluuebunny/crossref_metadata_2025 huggingface dataset:
Two Can Play That Game
Authors: Shah Ankit , Sinha Arunesh , Ganesan Rajesh , Jajodia Sushil , Cam Hasan
Published: April 2020

Cyber-security is an important societal concern. Cyber-attacks have increased in numbers as well as in the extent of damage caused in every attack. Large organizations operate a Cyber Security Operation Center (CSOC), which forms the first line of cyber-defense. The inspection of cyber-alerts is a critical part of CSOC operations (defender or blue team). Recent work proposed a reinforcement learning (RL) based approach for the defender’s decision-making to prevent the cyber-alert queue length from growing large and overwhelming the defender. In this article, we perform a red team (adversarial) evaluation of this approach. With the recent attacks on learning-based decision-making systems, it is even more important to test the limits of the defender’s RL approach. Toward that end, we learn several adversarial alert generation policies and the
best response
against them for various defender’s inspection policy. Surprisingly, we find the defender’s policies to be quite robust to the best response of the attacker. In order to explain this observation, we extend the earlier defender’s RL model to a game model with adversarial RL, and show that there exist defender policies that can be robust against any adversarial policy. We also derive a competitive baseline from the game theory model and compare it to the defender’s RL approach. However, when we go further to exploit the assumptions made in the Markov Decision Process (MDP) in the defender’s RL model, we discover an attacker policy that overwhelms the defender. We use a
double oracle
like approach to retrain the defender with episodes from this discovered attacker policy. This made the defender robust to the discovered attacker policy and no further harmful attacker policies were discovered. Overall, the adversarial RL and double oracle approach in RL are general techniques that are applicable to other RL usage in adversarial environments.
Experimental and Modeling Studies of 2D Clay/PE Nanocomposites for High Voltage Applications
Authors: Zazoum Bouchaib
Published: April 2020

The exceptional properties of two-dimensional (2D) nanoclay fillers can alter the dielectric and thermo-mechanical properties of the thermoplastic materials and consequently extend its engineering applications. In this work, polyethylene (PE) was filled with 2D organo-modified montmorillonite nanolcay (O-MMT) to fabricate polyethylene/clay nanocomposites. The dielectric properties of neat PE and its nanocomposites were investigated. The results indicated that the dielectric permittivity and breakdown strength were increased by the incorporation of the 2D nanoclay filler. Based on the achieved experimental results, 2D finite element model (FEM) was performed to explain the physical mechanisms behind the improved breakdown strength of the nanocomposites.
Expression and Significance of Immune Checkpoints in Clear Cell Carcinoma of the Uterine Cervix
Authors: Zong Liju , Zhang Qianqian , Zhou Yuncan , Kong Yujia , Yu Shuangni , Chen Jie , Zhang Youzhong , Xiang Yang
Published: April 2020

The purpose of this study was to investigate the expression levels of the immune checkpoint proteins, programmed cell death-ligand 1 (PD-L1), B7-H3, B7-H4, and V-domain Ig suppressor of T cell activation (VISTA), as well as the significance thereof, in clear cell carcinoma (CCC) of the cervix (a rare histological subtype of cervical cancer). We also compared the expression statuses of these biomarkers in cervical CCCs with those in cervical squamous cell carcinomas (SCCs). We evaluated the expression of PD-L1, B7-H3, B7-H4, and VISTA in 50 cervical CCCs and 100 SCCs using immunohistochemical staining and investigated the associations between these markers, clinicopathologic features, and survival in patients with CCCs. Of the cervical CCC samples examined, 22%, 16%, 32%, and 34% were positive for PD-L1, B7-H3, B7-H4, and VISTA, respectively. Nineteen samples (38%) were negative for all 4 of these markers, whereas 31 (62%) expressed at least 1 marker. None of these markers was associated with the investigated clinicopathologic variables or patient survival. PD-L1, B7-H3, and VISTA were observed significantly more frequently in SCCs than in CCCs of the cervix. Our study confirmed the expression of immune checkpoint proteins in cervical CCCs and indicated their nonredundant and complementary roles. As such, our data suggest that monotherapeutic immune checkpoint blockade may not be sufficiently effective in patients with cervical CCC.
Influence of Patient-Specific Head Modeling on EEG Source Imaging
Authors: Céspedes-Villar Yohan , Martinez-Vargas Juan David , Castellanos-Dominguez G.
Published: April 2020

Electromagnetic source imaging (ESI) techniques have become one of the most common alternatives for understanding cognitive processes in the human brain and for guiding possible therapies for neurological diseases. However, ESI accuracy strongly depends on the forward model capabilities to accurately describe the subject’s head anatomy from the available structural data. Attempting to improve the ESI performance, we enhance the brain structure model within the individual-defined forward problem formulation, combining the head geometry complexity of the modeled tissue compartments and the prior knowledge of the brain tissue morphology. We validate the proposed methodology using 25 subjects, from which a set of magnetic-resonance imaging scans is acquired, extracting the anatomical priors and an electroencephalography signal set needed for validating the ESI scenarios. Obtained results confirm that incorporating patient-specific head models enhances the performed accuracy and improves the localization of focal and deep sources.
KIF15 Promotes Proliferation and Growth of Hepatocellular Carcinoma
Authors: Sun Yue-Feng , Wu Hong-Li , Shi Rui-Fang , Chen Lin , Meng Chao
Published: April 2020

Liver cancer is thought as the most common human malignancy worldwide, and hepatocellular carcinoma (HCC) accounts for nearly 90% liver cancer. Due to its poor early diagnosis and limited treatment, HCC has therefore become the most lethal malignant cancers in the world. Recently, molecular targeted therapies showed great promise in the treatment of HCC, and novel molecular therapeutic targets is urgently needed. KIF15 is a microtubule-dependent motor protein involved in multiple cell processes, such as cell division. Additionally, KIF15 has been reported to participate in the growth of various types of tumors; however, the relation between KIF15 and HCC is unclear. Herein, our study investigated the possible role of KIF15 on the progression of HCC and found that KIF15 has high expression in tumor samples from HCC patients. KIF15 could play a critical role in the regulation of cell proliferation of HCC, which was proved by in vitro and in vivo assays. In conclusion, this study confirmed that KIF15 could be a novel therapeutic target for the treatment of HCC.
Activation of a Subset of Evolutionarily Young Transposable Elements and Innate Immunity Are Linked to Clinical Responses to 5-Azacytidine
Authors: Ohtani Hitoshi , Ørskov Andreas D. , Helbo Alexandra S. , Gillberg Linn , Liu Minmin , Zhou Wanding , Ungerstedt Johanna , Hellström-Lindberg Eva , Sun Weili , Liang Gangning , Jones Peter A. , Grønbæk Kirsten
Published: April 2020

The DNA methyltransferase inhibitors (DNMTi) 5-azacytidine and 5-aza-2-deoxycytidine have been approved for the treatment of different types of hematologic malignancies. However, only about 50% of patients respond to treatment. Therefore, a more comprehensive understanding of the molecular changes in patients treated with DNMTi is needed. Here, we examined gene expression profiles in a total of 150 RNA samples from two adult cohorts and one pediatric cohort with hematologic cancers taken before, during, and after treatment with 5-azacytidine (40 patients; 15 nonresponders, 25 responders). Using each patient as their own control, malignant cells showed preferential activation of a subset of evolutionarily young transposable elements (TE), including endogenous retroviral long terminal repeats (LTR), short and long interspersed nuclear elements (SINE and LINE), and the type I IFN pathway in responders, all independent of disease classification. Transfection of eight upregulated LTRs into recipient human cells in culture showed robust and heterogenous activation of six genes in the type I IFN pathway. These results, obtained in diverse hematologic disease entities, show that common targets (TE) activated by the same drug (5-azacytidine) elicit an immune response, which may be important for patient's responses to DNMTi.

Significance:

Activation of specific classes of evolutionarily young transposable elements can lead to activation of the innate immune system.
Higher Serum Vitamin D Concentrations Are Longitudinally Associated with Better Global Quality of Life and Less Fatigue in Colorectal Cancer Survivors up to 2 Years after Treatment
Authors: Koole Janna L. , Bours Martijn J.L. , van Roekel Eline H. , Breedveld-Peters José J.L. , van Duijnhoven Fränzel J.B. , van den Ouweland Jody , Breukink Stéphanie O. , Janssen-Heijnen Maryska L.G. , Keulen Eric T.P. , Weijenberg Matty P.
Published: April 2020

Background:

Vitamin D status may be an important determinant of health-related quality of life of colorectal cancer survivors. The current study investigated longitudinal associations between serum 25-hydroxyvitamin D3 (25OHD3) concentrations and quality of life in stage I–III colorectal cancer survivors up to 2 years after treatment.

Methods:

Patients with colorectal cancer (n = 261) were included upon diagnosis. Home visits (including blood sampling) were performed at diagnosis and at 6 weeks, 6 months, 1 year, and 2 years after treatment. Serum 25OHD3 concentrations were measured using LC/MS-MS and adjusted for season. Validated questionnaires were used to assess global quality of life and cognitive functioning (EORTC-QLQ-C30), fatigue (EORTC-QLQ-C30 and Checklist Individual Strength, CIS), and depression and anxiety (Hospital Anxiety and Depression Scale). Statistical analyses were performed using linear mixed models and adjusted for sex, age, time since diagnosis, therapy, comorbidities, physical activity, and body mass index.

Results:

At diagnosis, 45% of patients were vitamin D deficient (<50 nmol/L). After treatment, 25OHD3 concentrations increased on average with 3.1 nmol/L every 6 months. In confounder-adjusted models, 20 nmol/L increments in 25OHD3 were longitudinally associated with increased global quality of life [β 2.9; 95% confidence interval (CI), 1.5–4.3] and reduced fatigue (EORTC-QLQ-C30 subscale: β −3.5; 95% CI, −5.3 to −1.8 and CIS: β −2.8; 95% CI, −4.7 to −0.9). Observed associations were present both within and between individuals over time.

Conclusions:

Higher concentrations of 25OHD3 were longitudinally associated with better global quality of life and less fatigue in colorectal cancer survivors.

Impact:

This study suggests that higher 25OHD3 concentrations may be beneficial for colorectal cancer survivors. Future intervention studies are needed to corroborate these findings.
Investigations of Associations between Seven Gene Polymorphisms and Gestational Diabetes Mellitus: Evidence From a Meta-Analysis
Authors: Wang Bi , Xue Xiuping
Published: April 2020

Background: Associations of polymorphisms in transcription factor 7 like 2 (TCF7L2), tumor necrosis factor-α (TNF-α), vitamin D receptor (VDR), and interleukin-10 with gestational diabetes mellitus (GDM) were already reported by several publications. Objectives: The aim of this meta-analysis was to better clarify associations between these polymorphisms and GDM by combing the results of all relevant publications. Methods: Eligible publications were searched from Pubmed, Embase, WOS, and CNKI. We used Review Manager to combine the results of individual studies. Results: Thirty-nine studies were included in this study. Combined results revealed that TCF7L2 rs290487, TCF7L2rs7901695, TCF7L2rs7903146, TCF7L2 rs12255372, TNF-α rs1800629, and VDR FokI rs2228570 polymorphisms were all significantly associated with susceptibility to GDM in the total population. In subgroup analyses, we obtained similar positive findings for rs290487, rs7903146, rs1800629, and rs2228570 polymorphisms in Asians, and positive results were also observed for rs7901695, rs7903146, and rs12255372 polymorphisms in Caucasians. Conclusions: Collectively, this meta-analysis proved that TCF7L2 rs290487, TCF7L2rs7901695, TCF7L2rs7903146, TCF7L2 rs12255372, TNF-α rs1800629, and VDR FokI rs2228570 polymorphisms may confer susceptibility to GDM in certain populations.
Stereotactic Radiotherapy in Recurrent Glioblastoma: A Valid Salvage Treatment Option
Authors: Yaprak Gokhan , Isık Naciye , Gemici Cengiz , Pekyurek Melike , Ceylaner Bıcakcı Beyhan , Demircioglu Fatih , Tatarlı Necati
Published: April 2020

Background: Glioblastoma (GBM) is a dismal disease. Recurrence is inevitable despite initial surgery and postoperative temozolomide (TMZ) and radiotherapy. Salvage surgery is the standard treatment in selected patients. Chemotherapy, biological agents, and re-irradiation are other treatment approaches available. Stereotactic radiotherapy (SRT) is nowadays a common treatment as a salvage treatment option. Materials and Methods: We reviewed the files of 132 GBM cases treated between 2010 and 2018. All patients received TMZ and radiotherapy after surgery or biopsy. Among the patients who had recurrence, we identified 42 cases treated with salvage SRT. The CyberKnife robotic system was used to administer SRT. Results: While the median follow-up time for all patients was 16 months (range 1–123), the median follow-up time for patients treated with SRT after initial diagnosis was 26.5 months (range 9–123). The median follow-up time after SRT was 10 months (range 2–107). SRT was performed in a median of 3 fractions (range 2–5). The median prescription dose was 20 Gy (range 18–30). While the median actuarial survival after initial diagnosis for patients treated with salvage SRT was 30 months (range 9–123), it was only 14 months (range 1–111) for patients who could not be treated with salvage SRT (p = 0.001). The median survival time after SRT was 12 months, and 1- and 2-year survival rates were 48 and 9%, respectively. The time to progression after SRT was 5 months (range 1–62), and 6-month and 1-year progression-free survival rates were 50 and 22%, respectively. Patients with longer time to recurrence >12 months had longer overall survival with respect to the ones having recurrence <12 months (p < 0.001). Salvage surgery had been performed in 7 out of 42 patients before SRT. These reoperated patients had significantly worse survival after SRT when compared to the patients who underwent SRT alone (p = 0.02). SRT was well tolerated and there was no grade III/IV toxicity. Conclusions: SRT is a viable salvage treatment option for recurrent GBM. SRT provides acceptable local control and survival benefit for recurrent GBM cases. SRT can be considered especially in patients with long time to recurrence.
Enriched Environment Ameliorates Cognitive Deficits and Locomotor Sensitization in Morphine-Withdrawn Rats Receiving Methadone Maintenance Treatment
Authors: Akbari Parastoo , Najafi Mahmoud , Rezaei Ali-Mohammad , Miladi-Gorji Hossein
Published: April 2020

Objective: This study was designed to examine whether enriched environments (EE) would attenuate object recognition and spatial learning and memory deficits and locomotor sensitization induced by methadone maintenance treatment (MMT) in morphine-withdrawn rats. Methods: Male Wistar rats (170 ± 10 g) were injected with bi-daily doses (10 mg/kg, 12-h intervals) of morphine for 14 days. Rats receiving MMT were reared in the standard environment (SE) or EE during 30 days of morphine withdrawal. Then, the rats were tested for object recognition (the object recognition memory test, ORMT) and spatial learning and memory (the water maze) and then challenged with morphine (1 mg/kg, i.p.) and evaluated for locomotor activity (open-field box). Results: The results revealed that the dependent/saline/EE (D/Sal/EE) and D/methadone/EE (D/Meth/EE) rats exhibited significant preference for the new object (p = 0.006 and p = 0.049), spent more time in the target zone (p = 0.045 and p = 0.005) on the water maze, and displayed a lower level of distance traveled (p = 0.002 and p = 0.0001) compared to their control groups reared in SE. Conclusions: We conclude that exposure to EE could ameliorate the object recognition and spatial memory deficits and also decrease locomotor sensitivity in morphine-withdrawn rats receiving MMT. Thus, EE may be beneficial in the treatment of addiction during MMT.
Healthcare Consumption and Cost Estimates Concerning Swedish Women with Endometriosis
Authors: Grundström  Hanna , Hammar Spagnoli Gabriel , Lövqvist Lena , Olovsson Matts
Published: April 2020

Introduction: Endometriosis is known for its substantial effect on women’s wellbeing and quality of life. In order to evaluate disease burden, treatments and health services, assessments of healthcare consumption and cost estimates are necessary. Objectives: The aim of this study was to estimate healthcare consumption and annual cost per woman with endometriosis in Sweden and to examine healthcare consumption and costs in different age groups. Methods: A questionnaire was distributed to 400 members of the Endometriosis Association and to 400 randomly selected women with surgically confirmed endometriosis. Official statistics were obtained via correspondence, publications, and database searches. Results: Analysis of the 431 returned questionnaires showed that women under 30 years utilized more inpatient and outpatient care than older women. The mean annual cost among all women was EUR 8,768/woman. The direct healthcare cost of managing the disease was EUR 4,282, while the indirect cost was EUR 4,486. Absence from work was reported by 32% of the women, while 36% reported reduced time at work because of endometriosis. Conclusion: Our results confirm the substantial negative effect of endometriosis upon women’s lives and their relatively high healthcare consumption.
Linguística de corpus: teoria, perspetivas metodológicas e ensino das línguas
Authors: Assunção Carlos , Araújo Carla
Published: April 2020

A palavra ‛corpus’ reveste-se de ambiguidade, uma vez que diz respeito, por um lado, a um conjunto de dados e, por outro, a um conjunto de métodos. Em relação ao sentido de conjunto de dados, verifica-se que todos os linguistas são potenciais utilizadores de corpora, já que a Linguística é uma disciplina empírica. Os métodos sobre corpora, construídos a partir de simples concordâncias, são especialmente estatísticos e/ou probabilísticos. O contexto contemporâneo de ensino-aprendizagem das línguas impõe o desenvolvimento e a disponibilização de recursos didáticos, como as bases de dados que sirvam de suporte às exigentes e rigorosas práticas pedagógicas da conjuntura educativa do século XXI. Simultaneamente, este recurso permite ainda ao professor obter as competências necessárias para fomentar junto dos alunos uma atitude crítica e reflexiva sobre a língua, tendo em vista o desenvolvimento da capacidade de observação e análise da língua num processo de descoberta do seu sistema de funcionamento.
Reticent Digital Diasporas in Times of Crisis
Authors: Turner Simon , Berckmoes Lidewyde
Published: April 2020

Based on fieldwork amongst Burundians in Rwanda, the Netherlands and Belgium, this article explores how information circulates transnationally in times of political and violent crisis and how ordinary members of the diaspora seek to manage these flows of information. Our main argument is that conflict in the homeland creates a massive flow of information across various digital platforms and that while members of the diaspora eagerly take part in consuming and sharing this information, they do so reticently. Rather than simply explore the information flows, their intensity, their ‘spread’ or their content, we explore how individuals in the diaspora engage in emotion work, as they struggle between being ‘hailed’ by the images and messages flowing with ever-increasing intensity, speed and urgency and their reticence towards getting too involved.
Maladera rugosa (Blanchard, 1850) new combination—a valid species and senior synonym of Maladera graeca Petrovitz, 1969 (Coleoptera: Scarabaeidae: Melolonthinae: Sericini)
Authors: AHRENS DIRK , PACHECO THAYNARA L.
Published: April 2020

Maladera Mulsant & Rey, 1871 occurs in the Palaearctic, Oriental and Afrotropical regions and comprises already more than 300 species only in the Palaearctic alone (Ahrens & Bezděk 2016). In the past years the species of eastern West Palaearctic including Iran has been exhaustively explored and many new taxa were added (e.g. Ahrens 2000a,b, 2006; Ahrens et al. 2016; Fabrizi et al. 2018; Keith & Ahrens 2002; Keith 2005, 2010; Sabatinelli 1977; Sehnal 2008; Sehnal & Simandl 2008; Montreuil & Keith 2009; Montreuil 2016). While new collecting activities focused principally on the Iranian fauna (Nikodyìm & Král 1998; Keith & Ahrens 2002; Keith 2005, 2010; Montreuil & Keith 2009; Montreuil 2016), from where practically no records before the 1980s were available, no recent data were published on Maladera species of Europe and Minor Asia since the last taxonomic revision of the West Palaearctic species of the genus (Petrovitz 1969).
Revision of fossil Bibionidae (Insecta: Diptera) from the Miocene of Radoboj, Croatia
Authors: SKARTVEIT JOHN , KRIZMANIĆ KATARINA
Published: April 2020

We revise the available material of fossil bibionid flies from Radoboj, Croatia, and redescribe the species of which we have been able to locate material. We have found material of the following species: Penthetria anthracina (Heer, 1849), Penthetria cimicoides (Heer, 1849), Penthetria gracilis (Unger, 1841), Penthetria longa (Heer, 1849), Penthetria murchisonii (Unger, 1841), Plecia lugubris Heer, 1849, Plecia lygaeoides (Heer, 1849), Bibio crassinervis Skartveit & Pika, 2014, Bibio enterodelus Unger, 1841, Bibio firmus Heer, 1849, Bibio giganteus Unger, 1841 and Dilophus pinguis (Heer, 1849). Two species are shared with the approximately contemporary site of Öhningen, Southern Germany. Plecia bucklandi Heer, 1849 and Plecia morio (Heer, 1849) were recorded both from the Oligocene site of Aix-en-Provence, France and from Radoboj in the original descriptions, however we did not find any specimens from Radoboj conforming with the types from Aix-en-Provence.
A new species of Sasajiscymnus Vandenberg (Coleoptera: Coccinellidae) from Pakistan
Authors: IQBAL ZAFAR , NASIR MUHAMMAD FAROOQ , BODLAH IMRAN
Published: April 2020

A new species of a ladybird beetle, Sasajiscymnus nigritus sp. nov., is described and illustrated from Pakistan. An identification key to Pakistani species of Sasajiscymnus Vandenberg is provided. A preliminary checklist of species of Sasajiscymnus in Asia is also included.
New species of Tingidae (Insecta: Heteroptera) from Madagascar
Authors: GUILBERT ERIC
Published: April 2020

Surveys of Madagascar discovered five species new to science, described herein. A key to all species within the genera of these new species is provided, and the distribution of Malagasy Tingidae species is discussed.
Contribution to the knowledge of Chinese Cerconychia Klapálek (Plecoptera: Pteronarcyoidea: Styloperlidae) with a new synonym
Authors: ZHAO MENG-YUAN , HUO QING-BO , DU YU-ZHOU
Published: April 2020

Cerconychia Klapálek, 1913 is a genus of the Asian family Styloperlidae that is included in the superfamily Pteronarcyoidea. The genus currently includes five species that mainly occur southern and northwestern China, with one species also found in Vietnam. We recently examined specimens from Yunnan, Hainan, and Taiwan provinces, China and determined them as C. flectospina Wu 1962, C. sinensis Yang & Yang, 1995, and C brunnea Klapálek, 1913. We place Cerconychia sapa Stark & Sivec, 2007 as a junior subjective synonym of C. flectospina. We provide new images of the three species to facilitate identification.
A Method of Using WRF-Simulated Surface Temperature to Estimate Daily Evapotranspiration
Authors: Wang Dakang , Liu Yan , Yu Tao , Zhang Yin , Liu Qixin , Chen Xinran , Zhan Yulin
Published: April 2020

Surface temperature is one of the key parameters for estimating regional evapotranspiration (ET) based on the Surface Energy Balance System (SEBS) model using remote sensing data. However, continuous daily remote sensing surface temperature data are often not available due to the weather and environmental conditions. This paper proposed a scheme to obtain reliable ET that estimating ET using WRF-simulated surface skin temperature (TSK) and then modifying the deviation using the normalized difference vegetation index (NDVI). This study aims to explore whether the model data can be a viable option when the continuous-time-series remote sensing surface temperature is missing for estimating ET. Comparison results show that the correlation between WRF TSK and the measured temperature of the 2-cm soil (Ts) is better than MODIS land surface temperature (LST) in the study area, while the correlation between MODIS LST and the measured surface radiation temperature (IRT) is better than WRF TSK. The MODIS LST is significantly higher than Ts, and the WRF TSK is closer to Ts than MODIS LST. However, the ET calculated using WRF TSK was not good, exhibiting relatively high ET in the whole area and a poor correlation with the measurements, whereby R2, RMSE, and the percent bias (PBIAS) were equal to 0.1256, 5.2783 mm, and −202.17%, respectively. According to the principle of land surface process simulation in WRF, this paper proposes using NDVI to modify ET calculated using TSK. The comparison between the modified ET and the measurements exhibited a relatively good correlation, with R2 = 0.7532, RMSE = 1.0993 mm, and PBIAS = −17.9%. Therefore, the model surface temperature data can be used to estimate continuous-time-series regional ET when NDVI is used to modify the deviation, which indicates the surface temperature data simulated by the WRF Model can become the optional data for estimating ET and compensate for the shortcoming of poor time continuity of remote sensing data, further expanding the application prospects of meteorological model data in the remote sensing field.
Impact of bedside lung ultrasound on physician clinical decision-making in an emergency department in Nepal
Authors: House Darlene R. , Amatya Yogendra , Nti Benjamin , Russell Frances M.
Published: April 2020

Background

Lung ultrasound is an effective tool for the evaluation of undifferentiated dyspnea in the emergency department. Impact of lung ultrasound on clinical decisions for the evaluation of patients with dyspnea in resource-limited settings is not well-known. The objective of this study was to evaluate the impact of lung ultrasound on clinical decision-making for patients presenting with dyspnea to an emergency department in the resource-limited setting of Nepal.

Methods

A prospective, cross-sectional study of clinicians working in the Patan Hospital Emergency Department was performed. Clinicians performed lung ultrasounds on patients presenting with dyspnea and submitted ultrasounds with their pre-test diagnosis, lung ultrasound interpretation, post-test diagnosis, and any change in management.

Results

Twenty-two clinicians participated in the study, completing 280 lung ultrasounds. Diagnosis changed in 124 (44.3%) of patients with dyspnea. Clinicians reported a change in management based on the lung ultrasound in 150 cases (53.6%). Of the changes in management, the majority involved treatment (83.3%) followed by disposition (13.3%) and new consults (2.7%).

Conclusions

In an emergency department in Nepal, bedside lung ultrasound had a significant impact on physician clinical decision-making, especially on patient diagnosis and treatment.
Further development of the 12-item EDE-QS: identifying a cut-off for screening purposes
Authors: Prnjak Katarina , Mitchison Deborah , Griffiths Scott , Mond Jonathan , Gideon Nicole , Serpell Lucy , Hay Phillipa
Published: April 2020

Background

The Eating Disorder Examination – Questionnaire Short (EDE-QS) was developed as a 12-item version of the Eating Disorder Examination Questionnaire (EDE-Q) with a 4-point response scale that assesses eating disorder (ED) symptoms over the preceding 7 days. It has demonstrated good psychometric properties at initial testing. The purpose of this brief report is to determine a threshold score that could be used in screening for probable ED cases in community settings.

Methods

Data collected from Gideon et al. (2016) were re-analyzed. In their study, 559 participants (80.86% female; 9.66% self-reported ED diagnosis) completed the EDE-Q, EDE-QS, SCOFF, and Clinical Impairment Assessment (CIA). Discriminatory power was compared between ED instruments using receiver operating characteristic (ROC) curve analyses.

Results

A score of 15 emerged as the threshold that ensured the best trade-off between sensitivity (.83) and specificity (.85), and good positive predictive value (.37) for the EDE-QS, with discriminatory power comparable to other ED instruments.

Conclusion

The EDE-QS appears to be an instrument with good discriminatory power that could be used for ED screening purposes.
Adaptive Fisher method detects dense and sparse signals in association analysis of SNV sets
Authors: Cai Xiaoyu , Chang Lo-Bin , Potter Jordan , Song Chi
Published: April 2020

Background

With the development of next generation sequencing (NGS) technology and genotype imputation methods, statistical methods have been proposed to test a set of genomic variants together to detect if any of them is associated with the phenotype or disease. In practice, within the set, there is an unknown proportion of variants truly causal or associated with the disease. There is a demand for statistical methods with high power in both dense and sparse scenarios, where the proportion of causal or associated variants is large or small respectively.

Results

We propose a new association test – weighted Adaptive Fisher (wAF) that can adapt to both dense and sparse scenarios by adding weights to the Adaptive Fisher (AF) method we developed before. Using simulation, we show that wAF enjoys comparable or better power to popular methods such as sequence kernel association tests (SKAT and SKAT-O) and adaptive SPU (aSPU) test. We apply wAF to a publicly available schizophrenia dataset, and successfully detect thirteen genes. Among them, three genes are supported by existing literature; six are plausible as they either relate to other neurological diseases or have relevant biological functions.

Conclusions

The proposed wAF method is a powerful disease-variants association test in both dense and sparse scenarios. Both simulation studies and real data analysis indicate the potential of wAF for new biological findings.
Pseudogene-gene functional networks are prognostic of patient survival in breast cancer
Authors: Smerekanych Sasha , Johnson Travis S. , Huang Kun , Zhang Yan
Published: April 2020

Background

Given the vast range of molecular mechanisms giving rise to breast cancer, it is unlikely universal cures exist. However, by providing a more precise prognosis for breast cancer patients through integrative models, treatments can become more individualized, resulting in more successful outcomes. Specifically, we combine gene expression, pseudogene expression, miRNA expression, clinical factors, and pseudogene-gene functional networks to generate these models for breast cancer prognostics. Establishing a LASSO-generated molecular gene signature revealed that the increased expression of genes STXBP5, GALP and LOC387646 indicate a poor prognosis for a breast cancer patient. We also found that increased CTSLP8 and RPS10P20 and decreased HLA-K pseudogene expression indicate poor prognosis for a patient. Perhaps most importantly we identified a pseudogene-gene interaction, GPS2-GPS2P1 (improved prognosis) that is prognostic where neither the gene nor pseudogene alone is prognostic of survival. Besides, miR-3923 was predicted to target GPS2 using miRanda, PicTar, and TargetScan, which imply modules of gene-pseudogene-miRNAs that are potentially functionally related to patient survival.

Results

In our LASSO-based model, we take into account features including pseudogenes, genes and candidate pseudogene-gene interactions. Key biomarkers were identified from the features. The identification of key biomarkers in combination with significant clinical factors (such as stage and radiation therapy status) should be considered as well, enabling a specific prognostic prediction and future treatment plan for an individual patient. Here we used our PseudoFuN web application to identify the candidate pseudogene-gene interactions as candidate features in our integrative models. We further identified potential miRNAs targeting those features in our models using PseudoFuN as well. From this study, we present an interpretable survival model based on LASSO and decision trees, we also provide a novel feature set which includes pseudogene-gene interaction terms that have been ignored by previous prognostic models. We find that some interaction terms for pseudogenes and genes are significantly prognostic of survival. These interactions are cross-over interactions, where the impact of the gene expression on survival changes with pseudogene expression and vice versa. These may imply more complicated regulation mechanisms than previously understood.

Conclusions

We recommend these novel feature sets be considered when training other types of prognostic models as well, which may provide more comprehensive insights into personalized treatment decisions.
Choroidal vascularity index as a biomarker of systemic inflammation in childhood Polyarteritis Nodosa and adenosine deaminase-2 deficiency
Authors: BAYTAROĞLU Ata , KADAYIFÇILAR Sibel , AĞIN Abdullah , DELİKTAŞ Özge , DEMİR Selcan , BİLGİNER Yelda , KARAKAYA Jale , ÖZEN Seza , ELDEM Bora
Published: April 2020

Background/purpose

To assess EDI-OCT (enhanced depth imaging optical coherence tomography) of choroid for inflammatory signs in children with polyarteritis nodosa (PAN) and adenosine deaminase-2 deficiency (DADA-2).

Methods

In this cross-sectional study conducted between June 2017 and September 2018, we evaluated children diagnosed with PAN (n = 11) and DADA-2 (n = 4) and an age- and sex-matched control group (n = 15). Demographic and laboratory data were retrospectively analyzed from patient charts. Disease activity was assessed using the pediatric vasculitis activity score (PVAS). Choroidal images were obtained with spectral domain-OCT to measure choroidal thickness (ChT) at 5 points (750 and 1500 μm from the foveal center in the temporal and nasal quadrants and beneath the fovea), and to calculate the total subfoveal choroidal area (TCA), luminal area (LA), stromal area (SA), and the choroidal vascularity index (CVI).

Results

The median (min-max) age was 8 (4–16) years in PAN patients, 6 (5–16) years in DADA-2 patients and 8 (8–10) years in control group at the OCT visit (p = 0.214). The ChT at 3 points and the TCA, LA, and SA were higher in children with both PAN and DADA-2 patients compared to those of the control group (p < 0.0001, p = 0.049, p = 0.007, p = 0.007, p = 0.006, p = 0.033, respectively). The CVI was similar in both groups. No association was observed between the OCT findings, PVAS, and the erythrocyte sedimentation rate, and serum leukocyte and C-reactive protein levels.

Conclusion

Similar CVI scores were obtained from PAN and DADA2 patients under treatment and from healthy controls. Increased subfoveal ChT without any other signs of ocular involvement may suggest choroidal thickening as a sign of mild subclinical inflammation.
A rare face of follicular lymphoma: reverse variant of follicular lymphoma
Authors: Maskey Ninu , Chen Qiongrong , Liu Fang , Liu Shangqin , Tian Sufang
Published: April 2020

Background

Reverse Variant of Follicular Lymphoma (RVFL) is one of the rare morphological variants of FL, characterized by dark staining small centrocytes in the center and pale staining large centroblasts at the periphery of the neoplastic follicles. Only rare cases of RVFL have been described to date. The histological appearance of this little known variant of FL may be misinterpreted if pathologists are unaware of its existence. The main purpose of this study is to draw pathologists’ attention to such an uncommon growth pattern of FL so that this variant can be correctly recognized and the clinical significance further studied in the future.

Methods

Four cases of FL with unusual morphologic features were evaluated for the expression pattern of CD20, CD10, BCL6, BCL2, CD21, CD23, CD3, CD5, Cyclin D1, IgD and Ki67 by immunohistochemistry. Fluorescence in situ hybridization (FISH) with break-apart probes was performed to detect BCL2 gene rearrangement.

Results

All four cases showed distinctive morphologic pattern of RVFL; in addition, each also exemplified unique morphological features. Immunohistochemical stains confirmed the cells in both the central areas and the peripheral cuffs had the same immunophenotypic profiles, contrasting to the FL with marginal zone differentiation in which only the center of the nodules showed expression of CD10. FISH demonstrated BCL2 gene rearrangement in all cases.

Conclusion

The growth pattern of this rare FL variant may mimic FL with marginal-zone differentiation and other entities including but not limited to marginal zone lymphoma (MZL), progressive transformation of germinal centers (PTGC) and nodular lymphocyte predominant Hodgkin lymphoma (NLPHL). Pathologists should be familiar with this unusual morphological variant to avoid diagnostic pitfalls.
A primary neuroendocrine tumor of the left ventricle presenting with diarrhea—an unusual experience and literature review
Authors: Li Chengfang , Huang Jiajia , Yang Xiaorong , Xia Jinhua , Xu Gaoqiang , Zheng Hong
Published: April 2020

Background

Neuroendocrine tumors (NETs) can secrete bioactive amines in the bloodstream, resulting in the carcinoid syndrome characterized by diarrhea and flushing. The frequency of occurrence of primary cardiac neuroendocrine neoplasms is lesser than that of metastases, and hence, metastases must be adequately ruled out before diagnosis. Cardiac tumors, both primary and metastatic, mainly result in heart-related symptoms, such as heart failure and acquired valvular dysfunction. Here, we report a unique case of a primary left ventricular neuroendocrine tumor presenting with diarrhea.

Case presentation

A 51-year-old female complaining of intermittent diarrhea for 2 years was admitted to our hospital. Enhancement of total abdominal computed tomography scan, echocardiography, and magnetic resonance imaging indicated a mass in the left ventricle. The indexes of myocardial enzymes were normal. Histologically, round cells with well-differentiated neuroendocrine morphology were arranged in typical pseudo-glandular, trabecular, ribbon-like, and solid nest patterns. Immunohistochemically, the tumor cells were positive for cytokeratin, chromogranin, synaptophysin, and CD56. However, they were negative for caudal type homeobox 2, S100, paired box gene 8, thyroid transcription factor 1, and CD20, which ruled out the origin of gastrointestinal, pancreatic, lung, and Merkel cell carcinomas. The symptoms of diarrhea disappeared after the operation. The patient was asymptomatic at the 9-month follow-up.

Conclusion

Cardiac neuroendocrine tumors with diarrhea are considerably rare and related clinical research is limited. We presented a case and reviewed related articles to improve the identification, diagnosis, and management of patients with cardiac neuroendocrine tumors. The site of origin of a neuroendocrine tumor is clinically vital, and identification of an occult primary tumor using imaging modalities is necessary. Immunohistochemistry is well-suited to indicate the origin of the tumor. Regular follow-up is necessary for both poorly differentiated and well-differentiated cardiac neuroendocrine tumors. It is suggested to detect some neuroendocrinal markers for patients with unexplained reasons of diarrhea.
Identification and characterization of an R-Smad homologue (Hco-DAF-8) from Haemonchus contortus
Authors: Li Fang-Fang , Gasser Robin B. , Liu Feng , Shan Jia-Nan , Di Wen-Da , He Li , Zhou Cai-Xian , Wang Chun-Qun , Fang Rui , Hu Min
Published: April 2020

Background

Smad proteins are essential cellular mediators within the transforming growth factor-β (TGF-β) superfamily. They directly transmit incoming signals from the cell surface receptors to the nucleus. In spite of their functional importance, almost nothing is known about Smad proteins in parasitic nematodes includingHaemonchus contortus, an important blood-sucking nematode of small ruminants.

Methods

Based on genomic and transcriptome data forH. contortusand using bioinformatics methods, a Smad homologue (calledHco-daf-8) was inferred fromH.contortusand the structural characteristics of this gene and its encoded proteinHco-DAF-8 established. Using real-time PCR and immunofluorescence assays, temporal transcriptional and spatial expression profiles ofHco-daf-8were studied. Gene rescue inCaenorhabditis eleganswas then applied to assess the function ofHco-daf-8and a specific inhibitor of human Smad3 (called SIS3) was employed to evaluate the roles ofHco-DAF-8 inH. contortusdevelopment.

Results

The features ofHco-DAF-8 (502 amino acids), including conserved R-Smad domains and residues of the L3-loop that determine pathway specificity, are consistent with a TGF-β type I receptor-activated R-Smad. TheHco-daf-8gene was transcribed in all developmental stages ofH. contortusstudied, with a higher level of transcription in the fourth-stage larval (L4) females and the highest level in adult males.Hco-DAF-8 was expressed in the platymyarian muscular cells, intestine and reproductive system of adult stages. Gene rescue experiments showed thatHco-daf-8was able to partially rescue gene function in adaf-8deficient mutant strain ofC. elegans, leading to a resumption of normal development. InH. contortus, SIS3 was shown to affectH. contortusdevelopment from the exsheathed third-stage larvae (L3s) to L4sin vitro.

Conclusions

These findings suggest thatHco-DAF-8, encoded by the geneHco-daf-8, is an important cellular mediator ofH. contortusdevelopmentviathe TGF-β signalling pathway. They provide a basis for future explorations ofHco-DAF-8 and associated pathways inH. contortusand other important parasitic nematodes.
Detection of DNA of Babesia canis in tissues of laboratory rodents following oral inoculation with infected ticks
Authors: Corduneanu Alexandra , Ursache Teodor Dan , Taulescu Marian , Sevastre Bogdan , Modrý David , Mihalca Andrei Daniel
Published: April 2020

Background

Babesia spp. are apicomplexan parasites which infect a wide range of mammalian hosts. Historically, most Babesia species were described based on the assumed host specificity and morphological features of the intraerythrocytic stages. New DNA-based approaches challenge the traditional species concept and host specificity in Babesia. Using such tools, the presence of Babesia DNA was reported in non-specific mammalian hosts, including B. canis in feces and tissues of insectivorous bats, opening questions on alternative transmission routes. The aim of the present study was to evaluate if B. canis DNA can be detected in tissues of laboratory rodents following oral inoculation with infected ticks.

Methods

Seventy-five questing adult Dermacentor reticulatus ticks were longitudinally cut in two halves and pooled. Each pool consisted of halves of 5 ticks, resulting in two analogous sets. One pool set (n = 15) served for DNA extraction, while the other set (n = 15) was used for oral inoculation of experimental animals (Mus musculus, line CD-1 and Meriones unguiculatus). Blood was collected three times during the experiment (before the inoculation, at 14 days post-inoculation and at 30 days post-inoculation). All animals were euthanized 30 days post-inoculation. At necropsy, half of the heart, lung, liver, spleen and kidneys were collected from each animal. The presence of Babesia DNA targeting the 18S rRNA gene was evaluated from blood and tissues samples. For histopathology, the other halves of the tissues were used. Stained blood smears were used for the light microscopy detection of Babesia.

Results

From the 15 pools of D. reticulatus used for the oral inoculation, six were PCR-positive for B. canis. DNA of B. canis was detected in blood and tissues of 33.3% of the animals (4 out of 12) inoculated with a B. canis-positive pool. No Babesia DNA was detected in the other 18 animals which received B. canis-negative tick pools. No Babesia was detected during the histological examination and all blood smears were microscopically negative.

Conclusions

Our findings demonstrate that B. canis DNA can be detected in tissues of mammalian hosts following ingestion of infected ticks and opens the question of alternative transmission routes for piroplasms.
Assessing the impact of limiting Indonesian palm oil exports to the European Union
Authors: Rifin Amzul , Feryanto  , Herawati  , Harianto
Published: April 2020

The latest challenge faced by the Indonesian palm oil industry concerns the Delegated Act that has been adopted to limit the use of palm oil in biofuels because palm oil is considered to not support the sustainable development program. The objective of this article is to assess the suspension of Indonesia’s palm exports to the European Union in terms of Indonesia’s economic conditions. The Global Trade Analysis Project (GTAP) model is used to assess the impact, and the results indicate that the suspension will not create significant impacts on the economic growth, GDP, macro-welfare, and exports and imports of Indonesia.
Favorable response to pembrolizumab after durvalumab failure in a stage III sarcomatoid carcinoma of the lung: a case report
Authors: Nishino Kazumi , Kunimasa Kei , Kimura Madoka , Inoue Takako , Tamiya Motohiro , Kuhara Hanako , Kumagai Toru
Published: April 2020

Background

Pulmonary sarcomatoid carcinoma is a rare non-small-cell lung cancer (NSCLC) subtype with a poor prognosis. In the phase III PACIFIC study, durvalumab significantly improved progression-free survival and overall survival versus placebo, in patients with stage III NSCLC who do not have disease progression after concurrent chemoradiotherapy. However, treatments for patients who discontinue durvalumab due to disease progression, are unknown.

Case presentation

We report a case of favorable response to pembrolizumab in a patient with disease progression during durvalumab consolidation therapy after chemoradiotherapy for stage III pulmonary sarcomatoid carcinoma with high programmed cell death ligand 1 (PD-L1) and PD-L2 expression.

Conclusion

Here, we present what, to the best of our knowledge, is the first reported case in which durvarumab resistance after definitive chemoradiotherapy in a patient with stage III pulmonary sarcomatoid carcinoma was overcome by pembrolizumab.