bluuebunny/crossref_metadata_2025 huggingface dataset:
Link between increased cellular senescence and extracellular matrix changes in COPD
Authors: Woldhuis Roy R. , de Vries Maaike , Timens Wim , van den Berge Maarten , Demaria Marco , Oliver Brian G. G. , Heijink Irene H. , Brandsma Corry-Anke
Published: May 2020

Chronic obstructive pulmonary disease (COPD) is associated with features of accelerated aging, including cellular senescence, DNA damage, oxidative stress, and extracellular matrix (ECM) changes. We propose that these features are particularly apparent in patients with severe, early-onset (SEO)-COPD. Whether fibroblasts from COPD patients display features of accelerated aging and whether this is also present in relatively young SEO-COPD patients is unknown. Therefore, we aimed to determine markers of aging in (SEO)-COPD-derived lung fibroblasts and investigate the impact on ECM. Aging hallmarks and ECM markers were analyzed in lung fibroblasts from SEO-COPD and older COPD patients and compared with fibroblasts from matched non-COPD groups ( n = 9–11 per group), both at normal culture conditions and upon Paraquat-induced senescence. COPD-related differences in senescence and ECM expression were validated in lung tissue. Higher levels of cellular senescence, including senescence-associated β-galactosidase (SA-β-gal)-positive cells (19% for COPD vs. 13% for control) and p16 expression, DNA damage (γ-H2A.X-positive nuclei), and oxidative stress ( MGST1) were detected in COPD compared with control-derived fibroblasts. Most effects were also different in SEO-COPD, with SA-β-gal-positive cells only being significant in SEO-COPD vs. matched controls. Lower decorin expression in COPD-derived fibroblasts correlated with higher p16 expression, and this association was confirmed in lung tissue. Paraquat treatment induced cellular senescence along with clear changes in ECM expression, including decorin. Fibroblasts from COPD patients, including SEO-COPD, display higher levels of cellular senescence, DNA damage, and oxidative stress. The association between cellular senescence and ECM expression changes may suggest a link between accelerated aging and ECM dysregulation in COPD.
Renal ischemia alters expression of mitochondria-related genes and impairs mitochondrial structure and function in swine scattered tubular-like cells
Authors: Farahani Rahele A. , Zhu Xiang-Yang , Tang Hui , Jordan Kyra L. , Lerman Lilach O. , Eirin Alfonso
Published: May 2020

Scattered tubular-like cells (STCs) are dedifferentiated surviving tubular epithelial cells that repair neighboring injured cells. Experimental renal artery stenosis (RAS) impairs STC reparative potency by inducing mitochondrial injury, but the exact mechanisms of mitochondrial damage remain unknown. We hypothesized that RAS alters expression of mitochondria-related genes, contributing to mitochondrial structural damage and dysfunction in swine STCs. CD24+/CD133+STCs were isolated from pig kidneys after 10 wk of RAS or sham ( n = 3 each). mRNA sequencing was performed, and nuclear DNA (nDNA)-encoded mitochondrial genes and mitochondrial DNA (mtDNA)-encoded genes were identified. Mitochondrial structure, ATP generation, biogenesis, and expression of mitochondria-associated microRNAs were also assessed. There were 96 nDNA-encoded mitochondrial genes upregulated and 12 mtDNA-encoded genes downregulated in RAS-STCs versus normal STCs. Functional analysis revealed that nDNA-encoded and mtDNA-encoded differentially expressed genes were primarily implicated in mitochondrial respiration and ATP synthesis. Mitochondria from RAS STCs were swollen and showed cristae remodeling and loss and decreased ATP production. Immunoreactivity of the mitochondrial biogenesis marker peroxisome proliferator-activated receptor-γ coactivator (PGC)-1α and expression of the mitochondria-associated microRNAs miR-15a, miR-181a, miR-196a, and miR-296-3p, which target several mtDNA genes, were higher in RAS-STCs compared with normal STCs, suggesting a potential modulation of mitochondria-related gene expression. These results demonstrate that RAS induces an imbalance in mtDNA- and nDNA-mitochondrial gene expression, impairing mitochondrial structure and function in swine STCs. These observations support development of gene gain- and loss-of-function strategies to ameliorate mitochondrial damage and preserve the reparative potency of STCs in patients with renal ischemia.
14-3-3γ, a novel regulator of the large-conductance Ca2+-activated K+ channel
Authors: Chen Shan , Feng Xiuyan , Chen Xinxin , Zhuang Zhizhi , Xiao Jia , Fu Haian , Klein Janet D. , Wang Xiaonan H. , Hoover Robert S. , Eaton Douglas C. , Cai Hui
Published: May 2020

14-3-3γ is a small protein regulating its target proteins through binding to phosphorylated serine/threonine residues. Sequence analysis of large-conductance Ca2+-activated K+ (BK) channels revealed a putative 14-3-3 binding site in the COOH-terminal region. Our previous data showed that 14-3-3γ is widely expressed in the mouse kidney. Therefore, we hypothesized that 14-3-3γ has a novel role in the regulation of BK channel activity and protein expression. We used electrophysiology, Western blot analysis, and coimmunoprecipitation to examine the effects of 14-3-3γ on BK channels both in vitro and in vivo. We demonstrated the interaction of 14-3-3γ with BK α-subunits (BKα) by coimmunoprecipitation. In human embryonic kidney-293 cells stably expressing BKα, overexpression of 14-3-3γ significantly decreased BK channel activity and channel open probability. 14-3-3γ inhibited both total and cell surface BKα protein expression while enhancing ERK1/2 phosphorylation in Cos-7 cells cotransfected with flag-14-3-3γ and myc-BK. Knockdown of 14-3-3γ by siRNA transfection markedly increased BKα expression. Blockade of the ERK1/2 pathway by incubation with the MEK-specific inhibitor U0126 partially abolished 14-3-3γ-mediated inhibition of BK protein expression. Similarly, pretreatment of the lysosomal inhibitor bafilomycin A1 reversed the inhibitory effects of 14-3-3γ on BK protein expression. Furthermore, overexpression of 14-3-3γ significantly increased BK protein ubiquitination in embryonic kidney-293 cells stably expressing BKα. Additionally, 3 days of dietary K+ challenge reduced 14-3-3γ expression and ERK1/2 phosphorylation while enhancing renal BK protein expression and K+ excretion. These data suggest that 14-3-3γ modulates BK channel activity and protein expression through an ERK1/2-mediated ubiquitin-lysosomal pathway.
Breast Implant-Associated Anaplastic Large Cell Lymphoma
Authors: Moori P. L. , Ibison F. , Jacob D. , Iddon J.
Published: May 2020

Breast implant-associated anaplastic large cell lymphoma (BIA-ALCL) is a rare, non-Hodgkin lymphoma which arises within the capsules of breast implants. These particular tumours have expression of CD30 and are negative for Anaplastic Lymphoma Kinase (ALK). Here, we report a case of BIA-ALCL in a 48-year-old woman post breast reconstruction. This case report is aimed at raising awareness and education on the significance of considering the development of BIA-ALCL in cases where cytology is negative and helping better understand this disease process.
Spatiotemporal Evolution of Population in Northeast China during 2012–2017: A Nighttime Light Approach
Authors: You Haolin , Jin Cui , Sun Wei
Published: May 2020

Population is one of the key problematic factors that are restricting China’s economic and social development. Previous studies have used nighttime light (NTL) imagery to calculate population density. This study analyzes the spatiotemporal evolution of the population in Northeast China based on linear regression analyses of NPP-VIIRS NTL imagery and statistical population data from 36 cities in Northeast China from 2012 to 2017. Based on a comparison of the estimation results in different years, we observed the following. (1) The population of Northeast China showed an overall decreasing trend from 2012–2017, with population changes of +31,600, −960,800, −359,800, −188,000, and −1,127,600 in the respective years. (2) With the overall population loss trend in Northeast China, the population increased in only three cities, namely, Shenyang, Dalian, and Panjin, with an average increase during the six-year period of 24,200, 6,500, and 2,000 people, respectively. (3) The four major urban agglomerations in Northeast China (the Harbin-Daqing-Qiqihar Industrial Corridor, Changjitu Pilot Zone, Liaoning Coastal Economic Belt, and Shenyang Economic Zone) have annual populations far exceeding 4 million people. A correct appreciation of the population dynamics is vital to resource management and comprehensive management efforts. Making full use of natural resources and regional advantages could effectively improve and potentially solve the urban population loss problem and would be of great innovative significance for supporting the realization of the Millennium Development Goals.
Evolutionary Dynamics of Stochastic SEIR Models with Migration and Human Awareness in Complex Networks
Authors: Zhang Yue , Li Yuxuan
Published: May 2020

In this paper, a stochastic SEIR (Susceptible-Exposed-Infected-Removed) epidemic dynamic model with migration and human awareness in complex networks is constructed. The awareness is described by an exponential function. The existence of global positive solutions for the stochastic system in complex networks is obtained. The sufficient conditions are presented for the extinction and persistence of the disease. Under the conditions of disease persistence, the distance between the stochastic solution and the local disease equilibrium of the corresponding deterministic system is estimated in the time sense. Some numerical experiments are also presented to illustrate the theoretical results. Although the awareness introduced in the model cannot affect the extinction of the disease, the scale of the disease will eventually decrease as human awareness increases.
Abatacept in the Treatment of Juvenile Dermatomyositis-Associated Calcifications in a 16-Year-Old Girl
Authors: Sukumaran Sukesh , Vijayan Vini
Published: May 2020

Calcinosis is a feared complication of JDM that may be seen in up to 40% of children with JDM. It is associated with negative impact on the patients’ quality of life due to weakness, functional disability, joint contractures, muscle atrophy, skin ulcers, and secondary infections. Calcinosis can present as superficial nodules or plaques, larger nodular deposits extending into deeper tissue layers, accumulation of calcifications along the fascial planes of muscles or tendons, or an exoskeleton of calcium leading to limitations in mobility and joint contractures. Currently, there are no known effective treatments for calcinosis and current therapy is based on anecdotal retrospective studies and cases series. We report the case of a child with JDM-associated calcinosis with extensive intramuscular calcifications who failed conventional therapies but demonstrated improvement as evident by decrease in calcinosis and improved physical function with use of abatacept. We found that use of abatacept was associated with improvement in functional outcome and recurrence did not occur. This case suggests use of abatacept as a safe and effective treatment option for calcinosis due to JDM. Furthermore, large-scale clinical studies are needed to validate our findings and to evaluate the long-term outcomes.
Special Object Recognition Based on Sparse Representation in Multisource Data Fusion Samples
Authors: Zha Changjun
Published: May 2020

Wireless sensor networks (WSNs) suffer from limited power and large amounts of redundant data. This paper describes a multisource data fusion method for WSNs that can be combined with the characteristics of a profile detection system. First, principal component analysis is used to extract sample features and eliminate redundant information. Feature samples from different sources are then fused using a method of superposition to reduce the amount of data transmitted by the network. Finally, a mathematical model is proposed. On the basis of this model, a novel method of special object recognition based on sparse representation is developed for multisource data fusion samples according to the distribution of nonzero coefficients under an overcomplete dictionary. The experimental results from numerical simulations show that the proposed recognition method can effectively identify special objects in the fusion samples, and the overall performance is better than that of traditional methods.
Some Topological Notations via Maki’s Λ-Sets
Authors: Azzam A. A. , Nasef A. A.
Published: May 2020

Our purpose is to present the notions of a β-Λ-set and a β-V-sets in topological space. We discuss the basic properties of β-Λ-sets and β-V-sets. Also, the achievement of the topology defined by these families of sets is obtained. Finally, these results are applied to the case of X,τ which is the digital n-space Zn,Kn (cf. Section 4).
Application of Taiwan’s Human Rights-Themed Cultural Assets and Spatial Information
Authors: Lin Shuhui
Published: May 2020

Cultural assets preserve the traces of people’s life history around the world. With an understanding of the historical context and meaning of cultural assets, people would cherish their value and then adopt appropriate cultural resource preservation strategies. Human rights as the universal value refer to the inalienable and basic rights of human beings. This article uses the National Cultural Assets Network to query Taiwan’s human rights-themed cultural assets, and I apply the spatial information technology of the DocuSky digital humanities academic research platform to draw the maps with GIS and visualization tools. Also, I apply spatial information to the academic research of human rights-themed cultural assets, aiming to deepen local cultural identity and unveiling that human studies influence spatial practice. Tourism is an important experience economy. Based on the value of Taiwan’s human rights-themed cultural assets, I plan to guide the human rights journey in Taipei to share Taiwan’s experience of happiness with the world, as well.
The Solvability of Fractional Elliptic Equation with the Hardy Potential
Authors: Gao Siyu , Huang Shuibo , Tian Qiaoyu , Ma Zhan-Ping
Published: May 2020

In this paper, we study the existence and nonexistence of solutions to fractional elliptic equations with the Hardy potential −Δsu−λu/x2s=ur−1+δgu,in Ω,ux>0,in Ω,ux=0,in ℝN∖Ω, where Ω⊂ℝN is a bounded Lipschitz domain with 0∈Ω, −Δs is a fractional Laplace operator, s∈0,1, N>2s, δ is a positive number, 2<r<rλ,s≡N+2s−2αλ/N−2s−2αλ+1, αλ∈0,N−2s/2 is a parameter depending on λ, 0<λ<ΛN,s, and ΛN,s=22sΓ2N+2s/4/Γ2N−2s/4 is the sharp constant of the Hardy–Sobolev inequality.
A New Volumetric CNN for 3D Object Classification Based on Joint Multiscale Feature and Subvolume Supervised Learning Approaches
Authors: Muzahid A. A. M. , Wan Wanggen , Hou Li
Published: May 2020

The advancement of low-cost RGB-D and LiDAR three-dimensional (3D) sensors has permitted the obtainment of the 3D model easier in real-time. However, making intricate 3D features is crucial for the advancement of 3D object classifications. The existing volumetric voxel-based CNN approaches have achieved remarkable progress, but they generate huge computational overhead that limits the extraction of global features at higher resolutions of 3D objects. In this paper, a low-cost 3D volumetric deep convolutional neural network is proposed for 3D object classification based on joint multiscale hierarchical and subvolume supervised learning strategies. Our proposed deep neural network inputs 3D data, which are preprocessed by implementing memory-efficient octree representation, and we propose to limit the full layer octree depth to a certain level based on the predefined input volume resolution for storing high-precision contour features. Multiscale features are concatenated from multilevel octree depths inside the network, aiming to adaptively generate high-level global features. The strategy of the subvolume supervision approach is to train the network on subparts of the 3D object in order to learn local features. Our framework has been evaluated with two publicly available 3D repositories. Experimental results demonstrate the effectiveness of our proposed method where the classification accuracy is improved in comparison to existing volumetric approaches, and the memory consumption ratio and run-time are significantly reduced.
Evolutionary Stability Analysis of the Coal Mine Safety Management System Governed by Delay and Impulsive Differential Equations
Authors: Bai Li , Wang Xinhua , Lu Rongwu , Yu Hao , Li Dan
Published: May 2020

Control of unsafe behaviors has always been a difficult point in Coal Mine Safety Management (CMSM). To study the regular pattern of behavior propagations in CMSM, a series of evolutionary dynamical system models are established by the delay and impulsive differential equations (DIDEs). The threshold constraints (TCs) and impulse responses in the models can accurately correspond to the actual inspection and supervision measures in safety management. Through the simulation analysis and comparison of the system stability, it can be concluded that some proper settings of the TCs and impulse responses bring satisfactory evolutionary stability. Based on the main results of this study, we put forward some decision-making suggestions on the control points and control strategies of unsafe behaviors in safety management.
Research on a Location Method for Complex Voltage Sag Sources Based on Random Matrix Theory
Authors: Wu Lizhen , Zhang Yongnian , Hao Xiaohong , Chen Wei
Published: May 2020

The precise location of voltage sag sources plays an important role in formulating a voltage sag governance plan and clarifying the responsibility for the accident. The traditional location method of voltage sag sources is difficult to establish a precise mathematical model and locate the complex voltage sag sources accurately in the complex distribution network. In order to solve these problems, a location method for complex voltage sag sources based on random matrix theory is proposed in this paper. Firstly, the augmented matrix is constructed based on the influence factor data and the operation state data of the distribution network as the data source matrix, and the statistical characteristics of each data are analyzed by using the random matrix theory to determine the suspicious area of voltage sag source. Then, the disturbance signal of each node in the suspicious area of voltage sag source is analyzed by using the atomic algorithm and disturbance active power method, and it can determine the location of each disturbance source in the complex voltage sag event and the cause of voltage sag at each node. Compared with the existing model-based methods, the proposed method in this paper is a data-driven approach, which does not need the physical model and topology information. Furthermore, it can reduce the amount of data and improve the analysis efficiency on the basis of determining the suspicious area of the voltage sag source. Finally, the examples are given to show that the proposed method can accurately locate the disturbance sources in complex voltage sag events.
The Diagnostic and Clinical Significance of TFE3 Immunohistochemical Nuclear Expression in Solitary Fibrous Tumour
Authors: Zhou Luting , Wang Anran , Yu Guoli , Zhou Jun , Xu Haimin , Wang Chaofu
Published: May 2020

The expression of TFE3 (transcription factor E3) in solitary fibrous tumours (SFTs) and their histologic mimickers was investigated, and the diagnostic value and clinical significance of TFE3 nuclear expression in SFTs were explored. Immunohistochemical analysis for TFE3 was performed on 50 cases of SFTs that were surgically resected. The controls were sample tissues from malignant peripheral nerve sheath tumour, synovial sarcoma, dedifferentiated liposarcoma, spindle cell lipoma, and dermatofibrosarcoma protuberans. The survival of patients with TFE3-positive and TFE3-negative expressions was assessed through the Kaplan-Meier analysis. In 44 of 50 (88%) SFTs, nuclear immunoreactivity for TFE3 was detected. The TFE3 expression was negative in all samples of synovial sarcoma, malignant peripheral nerve sheath tumour, dermatofibrosarcoma protuberans, and spindle cell lipoma and weakly positive in 2 of 10 cases of dedifferentiated liposarcoma. Fluorescence in situ hybridization (FISH) confirmed that the expression of the TFE3 protein is not caused by gene translocation. There was no statistical significance between the association of the TFE3 expression and SFT patient prognosis. Therefore, TFE3 is capable of enhancing the differential diagnosis of SFTs and their histologic mimickers and can be potentially used as a diagnostic marker. The findings also offer valuable insights into SFT diagnosis, aetiology, and associated molecular mechanisms.
The Unique Periodic Solution of Abel’s Differential Equation
Authors: Hua Ni
Published: May 2020

In this paper, the existence of a periodic solution for Abel’s differential equation is obtained first by using the fixed-point theorem. Then, by constructing the Lyapunov function, the uniqueness and stability of the periodic solution of the equation are obtained.
Insulin-Like Growth Factor-1 Receptor Expression and Disease Recurrence and Survival in Patients with Resected Pancreatic Ductal Adenocarcinoma
Authors: Du Chunxia , da Silva Annacarolina , Morales-Oyarvide Vicente , Dias Costa Andressa , Kozak Margaret M. , Dunne Richard F. , Rubinson Douglas A. , Perez Kimberly , Masugi Yohei , Hamada Tsuyoshi , Brais Lauren K. , Yuan Chen , Babic Ana , Ducar Matthew D. , Thorner Aaron R. , Aguirre Andrew , Kulke Matthew H. , Ng Kimmie , Clancy Thomas E. , Findeis-Hosey Jennifer J. , Chang Daniel T. , Hornick Jason L. , Fuchs Charles S. , Ogino Shuji , Koong Albert C. , Hezel Aram F. , Wolpin Brian M. , Nowak Jonathan A.
Published: May 2020

Background:

Insulin-like growth factor-1 receptor (IGF1R) signaling is important in pancreatic ductal adenocarcinoma (PDAC) biology, but little is known regarding IGF1R expression and patient characteristics and outcomes.

Methods:

In 365 patients with resected PDAC, we evaluated IGF1R protein expression using IHC on whole-slide sections and IGF1R genomic status using next-generation sequencing. Associations of IGF1R expression, measured by H-scores incorporating staining intensity and proportion of positive tumor cells, with disease-free survival (DFS) and overall survival (OS) were evaluated in 317 and 321 patients, respectively, using Cox regression adjusting for known prognostic factors.

Results:

Higher IGF1R expression in tumor cells was associated with worse DFS comparing highest versus lowest expression tertiles [median DFS, 10.8 vs. 16.1 months; adjusted hazard ratio (HR), 1.73; 95% confidence interval (CI), 1.24–2.44; Ptrend = 0.002] and worse OS (median OS, 17.4 vs. 25.8 months; HR, 1.39; 95% CI, 1.00–1.92; Ptrend = 0.046). The association between high IGF1R expression and reduced DFS was identified primarily among patients with a preoperative body mass index ≥25 kg/m2 (HR, 4.27; 95% CI, 2.03–8.96, comparing extreme tertiles; Pinteraction = 0.032). KRAS-mutant tumors had greater IGF1R expression, and IGF1R expression in tumor epithelium was inversely correlated with that in stromal cells. Mutations in IGF1R were infrequent, and no overt loss-of-function alterations were identified. Higher IGF1R expression was modestly associated with higher gene copy number (Pearson correlation coefficient = 0.26, P < 0.001).

Conclusions:

Higher IGF1R protein expression was associated with worse patient outcomes in resected PDAC.

Impact:

IGF1R expression in PDAC represents a potential biomarker to guide patient selection for more aggressive, multidrug regimens in the adjuvant setting.
Metabolic Syndrome, Physical Activity, and Inflammation: A Cross-Sectional Analysis of 110 Circulating Biomarkers in Japanese Adults
Authors: Van Alsten Sarah C. , Rabkin Charles S. , Sawada Norie , Shimazu Taichi , Charvat Hadrien , Yamaji Taiki , Inoue Manami , Kemp Troy J. , Pinto Ligia A. , Camargo M. Constanza , Tsugane Shoichiro , Song Minkyo
Published: May 2020

Background:

Metabolic syndrome (MetS) is a systemic inflammatory state. Low physical activity (PA) could modify this patho-physiology or act as an independent contributor to inflammation. Previous studies of both conditions have identified altered levels of inflammation- and immune-related proteins based on limited sets of candidate markers.

Methods:

We investigated associations of MetS and low PA with circulating inflammation markers in a stratified random sample of Japanese adults (N = 774, mean age 60.7 years) within the Japan Public Health Center-based Prospective Study (JPHC) Cohort II. AHA/NHLBI criteria were used to define MetS (19%) and the bottom quartile of PA was considered low. 110 circulating biomarkers, including cytokines, chemokines, and soluble receptors were measured by multiplex bead-based and proximity-extension assays. Associations of MetS and low PA with marker quantiles were adjusted for each other and for age, sex, study site, cigarette smoking, alcohol consumption, and blood sample fasting state by ordinal logistic regression. P values were corrected for FDR.

Results:

MetS was significantly associated with levels of six markers: IL18R1 [odds ratio 2.37; 95% confidence interval (CI), 1.45–3.87], CRP (2.07; 95% CI, 1.48–2.90), SAP (2.08; 95% CI, 1.47–2.95), CCL19/MIP3β (2.06; 95% CI, 1.48–2.88), CXCL12/SDF1α+β (0.48; 95% CI, 0.32–0.65), and CCL28 (0.44; 95% CI, 0.27–0.71). Low PA had no significant marker associations.

Conclusions:

Positively associated markers with MetS are mostly Th1 immune response–related and acute phase proteins, whereas negatively associated markers are generally Th2-related.

Impact:

MetS is associated with a broad range of alterations in immune and inflammatory biomarkers that may contribute to risks of various chronic diseases, independent of low PA.
A Systematic Literature Review of Whole Exome and Genome Sequencing Population Studies of Genetic Susceptibility to Cancer
Authors: Rotunno Melissa , Barajas Rolando , Clyne Mindy , Hoover Elise , Simonds Naoko I. , Lam Tram Kim , Mechanic Leah E. , Goldstein Alisa M. , Gillanders Elizabeth M.
Published: May 2020

The application of next-generation sequencing (NGS) technologies in cancer research has accelerated the discovery of somatic mutations; however, progress in the identification of germline variation associated with cancer risk is less clear. We conducted a systematic literature review of cancer genetic susceptibility studies that used NGS technologies at an exome/genome-wide scale to obtain a fuller understanding of the research landscape to date and to inform future studies. The variability across studies on methodologies and reporting was considerable. Most studies sequenced few high-risk (mainly European) families, used a candidate analysis approach, and identified potential cancer-related germline variants or genes in a small fraction of the sequenced cancer cases. This review highlights the importance of establishing consensus on standards for the application and reporting of variants filtering strategies. It also describes the progress in the identification of cancer-related germline variation to date. These findings point to the untapped potential in conducting studies with appropriately sized and racially diverse families and populations, combining results across studies and expanding beyond a candidate analysis approach to advance the discovery of genetic variation that accounts for the unexplained cancer heritability.
Comparison of Tissue-Based Molecular Markers in Younger versus Older Patients with Colorectal Neoplasia
Authors: Limburg Paul J. , Mahoney Douglas W. , Ahlquist David A. , Allawi Hatim T. , Johnson Scott C. , Kaiser Michael , Katerov Viatcheslav E. , Statz Sandra , Graham Rondell P. , Foote Patrick H. , Doering Karen A. , Burger Kelli N. , Lidgard Graham P. , Kisiel John B.
Published: May 2020

Background:

Emerging colorectal cancer trends demonstrate increased incidence and mortality in younger populations, prompting consideration of average-risk colorectal cancer screening initiation at age 45 versus 50 years. However, screening test performance characteristics in adults 45–49 years have been minimally described. To inform the biologic rationale for multi-target stool DNA (mt-sDNA) screening in younger patients, we analyzed and compared tissue levels of methylation (BMP3, NDRG4) and mutation (KRAS) markers included in the FDA-approved, mt-sDNA assay (Cologuard; Exact Sciences Corporation).

Methods:

Within 40–44, 45–49, and 50–64 year age groups, archived colorectal tissue specimens were identified for 211 sporadic colorectal cancer cases, 123 advanced precancerous lesions (APLs; adenomas >1 cm, high-grade dysplasia, ≥25% villous morphology, or sessile serrated polyp; 45–49 and 50–64 age groups only), and 204 histologically normal controls. Following DNA extraction, KRAS, BMP3, and NDRG4 were quantified using QuARTS assays, relative to ACTB (reference gene).

Results:

None of the molecular marker concentrations were significantly associated with age (P > 0.05 for all comparisons), with the exception of NDRG4 concentration in APL samples (higher in older vs. younger cases; P = 0.008). However, NDRG4 levels were also statistically higher in APL case versus normal control samples in both the 45–49 (P < 0.0001) and 50–64 (P < 0.0001) year age groups.

Conclusions:

Overall, these findings support the potential for earlier onset of average-risk colorectal cancer screening with the mt-sDNA assay.

Impact:

These novel data address an identified knowledge gap and strengthen the biologic basis for earlier-onset, average-risk screening with the mt-sDNA assay.
Menstrual Factors, Reproductive History, Hormone Use, and Urothelial Carcinoma Risk: A Prospective Study in the EPIC Cohort
Authors: Lujan-Barroso Leila , Botteri Edoardo , Caini Saverio , Ljungberg Börje , Roswall Nina , Tjønneland Anne , Bueno-de-Mesquita Bas , Gram Inger T. , Tumino Rosario , Kiemeney Lambertus A. , Liedberg Fredrik , Stocks Tanja , Gunter Marc J. , Murphy Neil , Cervenka Iris , Fournier Agnès , Kvaskoff Marina , Häggström Christel , Overvad Kim , Lund Eiliv , Waaseth Marit , Fortner Renée Turzanski , Kühn Tilman , Menéndez Virginia , Sánchez Maria-Jose , Santiuste Carmen , Perez-Cornago Aurora , Zamora-Ros Raul , Cross Amanda J. , Trichopoulou Antonia , Karakatsani Anna , Peppa Eleni , Palli Domenico , Krogh Vittorio , Sciannameo Veronica , Mattiello Amalia , Panico Salvatore , van Gils Carla H. , Onland-Moret N. Charlotte , Barricarte Aurelio , Amiano Pilar , Khaw Kay-Tee , Boeing Heiner , Weiderpass Elisabete , Duell Eric J.
Published: May 2020

Background:

Urothelial carcinoma is the predominant (95%) bladder cancer subtype in industrialized nations. Animal and epidemiologic human studies suggest that hormonal factors may influence urothelial carcinoma risk.

Methods:

We used an analytic cohort of 333,919 women from the European Prospective Investigation into Cancer and Nutrition Cohort. Associations between hormonal factors and incident urothelial carcinoma (overall and by tumor grade, tumor aggressiveness, and non–muscle-invasive urothelial carcinoma) risk were evaluated using Cox proportional hazards models.

Results:

During a mean of 15 years of follow-up, 529 women developed urothelial carcinoma. In a model including number of full-term pregnancies (FTP), menopausal status, and menopausal hormone therapy (MHT), number of FTP was inversely associated with urothelial carcinoma risk (HR≥5vs1 = 0.48; 0.25–0.90; Ptrend in parous women = 0.010) and MHT use (compared with nonuse) was positively associated with urothelial carcinoma risk (HR = 1.27; 1.03–1.57), but no dose response by years of MHT use was observed. No modification of HRs by smoking status was observed. Finally, sensitivity analyses in never smokers showed similar HR patterns for the number of FTP, while no association between MHT use and urothelial carcinoma risk was observed. Association between MHT use and urothelial carcinoma risk remained significant only in current smokers. No heterogeneity of the risk estimations in the final model was observed by tumor aggressiveness or by tumor grade. A positive association between MTH use and non–muscle-invasive urothelial carcinoma risk was observed.

Conclusions:

Our results support that increasing the number of FTP may reduce urothelial carcinoma risk.

Impact:

More detailed studies on parity are needed to understand the possible effects of perinatal hormone changes in urothelial cells.
Methodologic Considerations in Calculating and Analyzing Proportion of Time Covered as a Measure of Longitudinal Cancer Screening Adherence
Authors: Chubak Jessica , Anderson Melissa L. , Cook Andrea J. , Murphy Caitlin C. , Jackson Michael L. , Green Beverly B.
Published: May 2020

Background:

Proportion of time covered (PTC, or “covered time”) is a longitudinal measure of adherence to preventive health services, the use of which has increased in recent years. This measure is helpful for evaluating the success of delivering screening interventions over time. However, there are challenges and nuances in computing and interpreting PTC.

Methods:

In this manuscript, we describe some desired properties of PTC measures, challenges in achieving those, and potential solutions using hypothetical examples.

Results:

We propose a modified PTC measure (mPTC) to complement the standard, existing PTC measure. The mPTC measure focuses on screening completion rather than initiation when a screening modality requires more than one step; is affected less by loss to follow-up, death, or cancer during covered time than the standard PTC measure; and is not sensitive to screening episode results. We propose weighting strategies to ensure that the average PTC and mPTC are more heavily influenced by individuals who were observed for longer and are thus more informative. We further describe how PTC and mPTC measures can incorporate test indication to focus specifically on screening.

Conclusions:

We recommend that studies of covered time present ample descriptive information, calculate both PTC and mPTC, describe how symptoms and indication are handled, and present multiple complementary measures, such as the proportion never screened and the proportion in need of screening.

Impact:

Common approaches, terminology, and reporting practices for covered time measures have the potential to improve the study of longitudinal cancer screening adherence.
PRAS40 Phosphorylation Correlates with Insulin-Like Growth Factor-1 Receptor-Induced Resistance to Epidermal Growth Factor Receptor Inhibition in Head and Neck Cancer Cells
Authors: Dougherty Michael I. , Lehman Christine E. , Spencer Adam , Mendez Rolando E. , David Abel P. , Taniguchi Linnea E. , Wulfkuhle Julie , Petricoin Emanuel F. , Gioeli Daniel , Jameson Mark J.
Published: May 2020

EGFR inhibitors have shown poor efficacy in head and neck squamous cell carcinoma (HNSCC) with demonstrated involvement of the insulin-like growth factor-1 receptor (IGF1R) in resistance to EGFR inhibition. IGF1R activates the PI3K–Akt pathway, which phosphorylates proline-rich Akt substrate of 40 kDa (PRAS40) to cease mTOR inhibition resulting in increased mTOR signaling. Proliferation assays separated six HNSCC cell lines into two groups: sensitive to EGFR inhibition or resistant; all sensitive cell lines demonstrated reduced sensitivity to EGFR inhibition upon IGF1R activation. Reverse phase protein microarray analysis and immunoblot identified a correlation between increased PRAS40 phosphorylation and IGFR-mediated resistance to EGFR inhibition. In sensitive cell lines, PRAS40 phosphorylation decreased 44%–80% with EGFR inhibition and was restored to 98%–196% of control by IGF1R activation, while phosphorylation was unaffected in resistant cell lines. Possible involvement of mTOR in this resistance mechanism was demonstrated through a similar pattern of p70S6K phosphorylation. However, addition of temsirolimus, an mTORC1 inhibitor, was insufficient to overcome IGF1R-mediated resistance and suggested an alternative mechanism. Forkhead box O3a (FOXO3a), which has been reported to complex with PRAS40 in the cytoplasm, demonstrated a 6-fold increase in nuclear to cytoplasmic ratio upon EGFR inhibition that was eliminated with concurrent IGF1R activation. Transcription of FOXO3a-regulated TRAIL and PTEN-induced putative kinase-1 (PINK1) was increased with EGFR inhibition in sensitive cell lines; this effect was diminished with IGF1R stimulation.

Implications:

These data suggest PRAS40 may play an important role in IGF1R-based therapeutic resistance to EGFR inhibition, and this likely occurs via inhibition of FOXO3a-mediated proapoptotic gene transcription.
Inflammation-Induced Abnormal Expression of Self-molecules on Epithelial Cells: Targets for Tumor Immunoprevention
Authors: Jacqueline Camille , Lee Amanda , Frey Nolan , Minden Jonathan S. , Finn Olivera J.
Published: May 2020

Tumor-associated antigens (TAA) are self-molecules abnormally expressed on tumor cells, which elicit humoral and cellular immunity and are targets of immunosurveillance. Immunity to TAAs is found in some healthy individuals with no history of cancer and correlates positively with a history of acute inflammatory and infectious events and cancer risk reduction. This suggests a potential role in cancer immunosurveillance for the immune memory elicited against disease-associated antigens (DAA) expressed on infected and inflamed tissues that are later recognized on tumors as TAAs. To understand probable sources for DAA generation, we investigated in vitro the role of inflammation that accompanies both infection and carcinogenesis. After exposure of normal primary breast epithelial cells to proinflammatory cytokines IL1β, IL6, and TNFα, or macrophages producing these cytokines, we saw transient overexpression of well-known TAAs, carcinoembryonic antigen and Her-2/neu, and overexpression and hypoglycosylation of MUC1. We documented inflammation-induced changes in the global cellular proteome by 2D difference gel electrophoresis combined with mass spectrometry and identified seven new DAAs. Through gene profiling, we showed that the cytokine treatment activated NF-κB and transcription of the identified DAAs. We tested three in vitro–identified DAAs, Serpin B1, S100A9, and SOD2, and found them overexpressed in premalignant and malignant breast tissues as well as in inflammatory conditions of the colon, stomach, and liver. This new category of TAAs, which are also DAAs, represent a potentially large number of predictable, shared, immunogenic, and safe antigens to use in preventative cancer vaccines and as targets for cancer therapies.
Divinity, Noēsis, and Aristotelian Friendship
Authors: Houston John A.
Published: May 2020

Aristotle's NE X claim that the best human life is one devoted to contemplation (theoria) seems in tension with his emphasis elsewhere on our essentially political nature, and more specifically, his claim that friendship is necessary for our flourishing. For, if our good can be in principle realized apart from the human community, there seems little reason to suggest we 'need' friends, as he clearly does in NE VIII & IX. I argue that central to Aristotle's NE X discussion of contemplation is the claim that our chief good accords with whatever is 'most divine' in us, viz. our rational nature (NE 1177b2-18). Thus, the best human life involves the excellent exercise of our rational capacities. I distinguish two ways in which human beings flourish through exercising their rationality. The first is in the activity of theoria. The second, I argue, can be found in the virtuous activity of complete friendship (teleia philia). For Aristotle the truest form of friendship is an expression of rationality. It is characterized not merely by our living together, but conversing, and sharing one another's thoughts (NE 1170b12-14). Examining Aristotle's notion of a friend as 'another self (alios autos), I argue that through friendship human beings come to better know themselves and the world in which they live. Complete friendship involves a (uniquely human) second-order awareness of oneself in another, and through this awareness our understanding of ourselves and the world in which we live is enriched, confirmed, and enjoyed through the presence of other minds. Thus, the highest form of Aristotelian friendship is an intellectual activity through which we attain an analogue of the divine contemplation of the unmoved mover, thereby living with respect to what is most divine in us, but doing so in accordance with our uniquely rational-political nature.
COVID-19 publications: Database coverage, citations, readers, tweets, news, Facebook walls, Reddit posts
Authors: Kousha Kayvan , Thelwall Mike
Published: May 2020

The COVID-19 pandemic requires a fast response from researchers to help address biological, medical, and public health issues to minimize its impact. In this rapidly evolving context, scholars, professionals, and the public may need to identify important new studies quickly. In response, this paper assesses the coverage of scholarly databases and impact indicators during March 21, 2020 to April 18, 2020. The rapidly increasing volume of research is particularly accessible through Dimensions, and less through Scopus, the Web of Science, and PubMed. Google Scholar’s results included many false matches. A few COVID-19 papers from the 21,395 in Dimensions were already highly cited, with substantial news and social media attention. For this topic, in contrast to previous studies, there seems to be a high degree of convergence between articles shared in the social web and citation counts, at least in the short term. In particular, articles that are extensively tweeted on the day first indexed are likely to be highly read and relatively highly cited 3 weeks later. Researchers needing wide scope literature searches (rather than health-focused PubMed or medRxiv searches) should start with Dimensions (or Google Scholar) and can use tweet and Mendeley reader counts as indicators of likely importance.
Comparative home range size and habitat selection in provisioned and non-provisioned long-tailed macaques (Macaca fascicularis) in Baluran National Park, East Java, Indonesia
Authors: Hansen Malene F. , Ellegaard Signe , Moeller Maria M. , van Beest Floris M. , Fuentes Agustin , Nawangsari Ventie A. , Groendahl Carsten , Frederiksen Monica L. , Stelvig Mikkel , Schmidt Niels M. , Traeholt Carl , Dabelsteen Torben
Published: May 2020

The effect of food provisioning on ranging patterns of long-tailed macaques (Macaca fascicularis) in non-anthropogenic areas is largely unknown, as most published studies have focused on urban macaques. In this study, we quantified habitat selection, daily path length and home range size in long-tailed macaques in Baluran National Park, East Java, Indonesia, comparing a non-provisioned to a provisioned group. To track the groups, we deployed six GPS-collars on females in both groups, of which only two collected data. Home range size (90% Auto-correlated Kernel Density Estimate) was 23 times smaller for the provisioned group (10.62 ha) than the non-provisioned group (249.90 ha). Home range size and area changed from dry to wet season for the non-provisioned group. Provisioned group home range size correlated negatively with number of visitors in the national park. Daily path length was significantly higher for the non-provisioned group. The provisioned group preferred settlements, where most of the provisioning occurred, and avoided areas with invasive acacia (Acacia nilotica). The non-provisioned group also avoided invasive acacia, preferred secondary forest in the dry season and restored savannah in the wet season. Food provisioning can affect macaque spatial ecology, by shaping daily travel length and home range size, and changing patterns of habitat selection. Even tourism in a managed national park, where provisioning is strictly prohibited although not always enforced, has significant consequences for animal behaviour and their natural ecosystems.
Morpho-molecular characterization of two novel amphisphaeriaceous species from Yunnan, China

Authors: DISSANAYAKE LAKMALI S. , SAMARAKOON MILAN C. , MORTIMER PETER E. , LU YONG-ZHONG , LI QI-RUI , HYDE KEVIN D. , KANG JI-CHUAN
Published: May 2020

Amphisphaeria yunnanensis sp. nov. and Lepteutypa qujingensis sp. nov. are introduced in this study from dead twigs collected from an evergreen broadleaf forest area in Yunnan Province, China. Both species have immersed, sub-globose ascomata and overlapping uniseriate asci and multi-guttulate, fusiform, brown ascospores. Amphisphaeria yunnanensis is distinguished among similar taxa in having long and narrow ostiole and comparatively small fusiform ascospores. Lepteutypa qujingensis is characterized by smaller ascomata and ascospores compare to other Lepteutypa species. Based on LSU-ITS phylogeny and macro-micro morphology, both species are placed in Amphisphaeriaceae. Morphological comparisons of the accepted species in Amphisphaeria and Lepteutypa are provided.
Molecular phylogeny and diversification timing of the Chamaecrista sect. Absus subsect. Absus ser. Paniculatae, a newly circumscribed and predominantly endemic of the Cerrado Biome group

Authors: MENDES THAINARA POLICARPO , SOUZA ALESSANDRO OLIVEIRA DE , SILVA MARCOS JOSÉ DA
Published: May 2020

Chamaecrista is a monophyletic genus, comprises approximately 330 tropical species classified into six sections of which Chamaecrista sect. Absus is the largest of them with 190 species, four subsections, and 31 series. Series Paniculatae comprises seven species (13 taxa) mainly distributed in the Brazilian Savanna and has been pointed as a paraphyletic group in a preliminary study about Chamaecrista. We propose a phylogenetic reconstruction of Paniculatae in order to test its monophyly based on a larger sample, to verify its relationships with other series, and to better define its systematic position in the genus. We sampled 74 taxa: 68 species of Chamaecrista (including all species of the series Paniculatae), six of Senna, and one of Cassia. Phylogenetic relationships of this taxa were explored using Maximum Parsimony (MP) and Bayesian analyses of nuclear ITS and plastidial trnL-trnF sequences, and the divergence time was estimate. Paniculatae emerge as a paraphyletic group in all analyses. Consequently, we are herein redefining the series Paniculatae in a monophyletic group with 13 morphologically well-defined species, divided into two genetically and geographically structured subclades. Divergence time analyses suggested that the clade Paniculatae, as defined here, originated ca. 6.2 million years ago, and had two main diversification events consistent with the recovered subclades. We propose the ranking of the varieties belonging to Ch. claussenii, Ch. orbiculata and Ch. rigidifolia at the level of species supported by morphological characteristics and large ranges of distribution, as well as phylogenetic relationships observed. We believe that our results enhanced the understanding both origin of the species of Paniculatae series, as well as of local species distribution in the Cerrado Biome.
An annotated distributional checklist of Vespidae (Hymenoptera: Vespoidea) of India
Authors: GAWAS SANDESH M. , KUMAR P. GIRISH , PANNURE ARATI , GUPTA ANKITA , CARPENTER JAMES M.
Published: May 2020

This study presents a checklist of the vespid wasps (Hymenoptera: Vespidae) of India. A total of 288 species belonging to 60 genera and 5 subfamilies of Vespidae are known to occur within the political boundaries of India. A complete list of species, comprising valid scientific names, synonyms, geographical distribution within and outside India, along with references, is provided. One new synonymy is proposed.