bluuebunny/crossref_metadata_2025 huggingface dataset:
The Weisfeiler--Leman Dimension of Planar Graphs Is at Most 3
Authors: Kiefer Sandra , Ponomarenko Ilia , Schweitzer Pascal
Published: November 2019

We prove that the Weisfeiler--Leman (WL) dimension of the class of all finite planar graphs is at most 3. In particular, every finite planar graph is definable in first-order logic with counting using at most 4 variables. The previously best-known upper bounds for the dimension and number of variables were 14 and 15, respectively.

First, we show that, for dimension 3 and higher, the WL-algorithm correctly tests isomorphism of graphs in a minor-closed class whenever it determines the orbits of the automorphism group of every arc-colored 3-connected graph belonging to this class.

Then, we prove that, apart from several exceptional graphs (which have WL-dimension at most 2), the individualization of two appropriately chosen vertices of a colored 3-connected planar graph followed by the one-dimensional WL-algorithm produces the discrete vertex partition. This implies that the three-dimensional WL-algorithm determines the orbits of arc-colored 3-connected planar graphs.

As a byproduct of the proof, we get a classification of the 3-connected planar graphs with fixing number 3.
Network-based Fake News Detection
Authors: Zhou Xinyi , Zafarani Reza
Published: November 2019

Fake news gains has gained significant momentum, strongly motivating the need for fake news research. Many fake news detection approaches have thus been proposed, where most of them heavily rely on news content. However, networkbased clues revealed when analyzing news propagation on social networks is an information that has hardly been comprehensively explored or used for fake news detection. We bridge this gap by proposing a network-based pattern-driven fake news detection approach. We aim to study the patterns of fake news in social networks, which refer to the news being spread, spreaders of the news and relationships among the spreaders. Empirical evidence and interpretations on the existence of such patterns are provided based on social psychological theories. These patterns are then represented at various network levels (i.e., node-level, ego-level, triad-level, community-level and the overall network) for being further utilized to detect fake news. The proposed approach enhances the explainability in fake news feature engineering. Experiments conducted on real-world data demonstrate that the proposed approach can outperform the state of the arts.
Deficiency in ROS-sensing nuclear factor erythroid 2-like 2 causes altered glucose and lipid homeostasis following exercise training
Authors: Merry Troy L. , MacRae Caitlin , Pham Toan , Hedges Christopher P. , Ristow Michael
Published: November 2019

Oxidative stress induced by acute exercise may regulate exercise training-induced adaptations that improve metabolic health. One of the central transcription regulatory targets of reactive oxygen species (ROS) is Nrf2 (nuclear factor erythroid-derived 2-like 2, or NFE2L2). Here, we investigated whether global deficiency of Nrf2 in mice would impact exercise training-induced changes in glucose and lipid homeostasis. We report that following 6 wk of treadmill exercise training, Nrf2-deficient mice have elevated fasting plasma triglycerides and free fatty acids and higher blood glucose levels following a meal despite having a similar fat mass to wild-type controls. This impaired glucose homeostasis appears to be related to reduced insulin sensitivity primarily in adipose and liver tissue, and although a clear mechanism was not evident, Nrf2-deficient mice had increased markers of hepatic oxidative stress and stress-related kinase activation in white adipose tissue (WAT) without overt inflammation alteration in WAT or modulation of hepatic and WAT fibroblast growth factor 21 gene expression. Our results suggest that Nrf2 facilitates exercise training-induced improvements in glucose homeostasis; however, further research is required to determine whether this occurs through direct regulation of exercise adaptations or via the maintenance of redox balance during training.
Improved endothelial-dependent and endothelial-independent skin vasodilator responses following remote ischemic preconditioning
Authors: Kim Jahyun , Franke Warren D. , Lang James A.
Published: November 2019

One week of daily remote ischemic preconditioning (RIPC) improves cutaneous vasodilatory (VD) function. However, the underlying mechanisms and the number of sessions needed to optimize this adaptive response remain unclear. We hypothesized that the responses to localized heating of the skin will be greater after 2 wk as opposed to 1 wk of RIPC. Furthermore, 2 wk of repeated RIPC will augment cutaneous VD responses to thermal and pharmacological stimuli. In methods, twenty-four participants (24 ± 2 yr; 13 men, 11 women) performed repeated RIPC (7 daily sessions over 1 wk, n = 11; 12 sessions over 2 wk, n = 13), consisting of four repetitions of 5 min of arm blood flow occlusion separated by 5 min reperfusion. Laser speckle contrast imaging was used to measure skin blood flow responses, in perfusion units (PU), to local heating (Tloc = 42°C), acetylcholine (ACh), and sodium nitroprusside (SNP) before and after repeated RIPC. Data were expressed as cutaneous vascular conductance (CVC, in PU/mmHg). In results, the VD response to local heating increased after RIPC (∆CVC from baseline; 1 wk: 0.94 ± 0.11 to 1.19 ± 0.15, 2 wk: 1.18 ± 0.07 to 1.33 ± 0.10 PU/mmHg; P < 0.05) but the ∆CVC did not differ between weeks. SNP-induced VD increased after 2 wk of RIPC (∆CVC; 0.34 ± 0.07 to 0.63 ± 0.11 PU/mmHg; P < 0.05), but ACh-induced VD did not. In conclusion, repeated RIPC improves local heating- and SNP-mediated cutaneous VD. When compared with 1 wk of RIPC, 2 wk of RIPC does not induce further improvements in cutaneous VD function.

NEW & NOTEWORTHY Repeated RIPC increases the cutaneous vasodilatory response to local heating and to sodium nitroprusside but not to acetylcholine. Thus, endothelial-independent and local heating-mediated cutaneous vasodilation are improved following RIPC. However, 2 wk of RIPC sessions are not more effective than 1 wk of RIPC sessions in enhancing local heating-mediated cutaneous vasodilation.
Analysis of fibroblast migration dynamics in idiopathic pulmonary fibrosis using image-based scaffolds of the lung extracellular matrix
Authors: Tisler Marisa , Alkmin Samuel , Chang Hsin-Yu , Leet Jon , Bernau Ksenija , Sandbo Nathan , Campagnola Paul J.
Published: November 2019

Idiopathic pulmonary fibrosis (IPF) is characterized by a profound remodeling of the collagen in the extracellular matrix (ECM), where the fibers become both denser and more highly aligned. However, it is unknown how this reconfiguration of the collagen matrix affects disease progression. Here, we investigate the role of specific alterations in collagen fiber organization on cell migration dynamics by using biomimetic image-based collagen scaffolds representing normal and fibrotic lung, where the designs are derived directly from high-resolution second harmonic generation microscopy images. The scaffolds are fabricated by multiphoton-excited (MPE) polymerization, where the process is akin to three-dimensional printing, except that it is performed at much greater resolution (∼0.5 microns) and with collagen and collagen analogs. These scaffolds were seeded with early passaged primary human normal and IPF fibroblasts to enable the decoupling of the effect of cell-intrinsic characteristics (normal vs. IPF) versus ECM structure (normal vs. IPF) on migration dynamics. We found that the highly aligned IPF collagen structure promoted enhanced cell elongation and F-actin alignment along with increased cell migration speed and straightness relative to the normal tissues. Collectively, the data are consistent with an enhanced contact guidance mechanism on the aligned IPF matrix. Although cell intrinsic effects were observed, the aligned collagen matrix morphology had a larger effect on these metrics. Importantly, these biomimetic models of the lung cannot be synthesized by conventional fabrication methods. We suggest that the MPE image-based fabrication method will enable additional hypothesis-based testing studies of cell-matrix interactions in the context of tissue fibrosis.
The interactions between respiratory and cardiovascular systems in systolic heart failure
Authors: Cross Troy James , Kim Chul-Ho , Johnson Bruce D. , Lalande Sophie
Published: November 2019

Heart failure (HF) is a complex and multifaceted disease. The disease affects multiple organ systems, including the respiratory system. This review provides three unique examples illustrating how the cardiovascular and respiratory systems interrelate because of the pathology of HF. Specifically, these examples outline the impact of HF pathophysiology on 1) respiratory mechanics and the mechanical “cost” of breathing; 2) mechanical interactions of the heart and lungs; and on 3) abnormalities of pulmonary gas exchange during exercise, and how this may be applied to treatment. The goal of this review is to, therefore, raise the awareness that HF, though primarily a disease of the heart, is accompanied by marked pathology of the respiratory system.
Determinants of the esophageal-pleural pressure relationship in humans
Authors: Pasticci Iacopo , Cadringher Paolo , Giosa Lorenzo , Umbrello Michele , Formenti Paolo , Macri Matteo M. , Busana Mattia , Bonifazi Matteo , Romitti Federica , Vassalli Francesco , Cressoni Massimo , Quintel Michael , Chiumello Davide , Gattinoni Luciano
Published: November 2019

Esophageal pressure has been suggested as adequate surrogate of the pleural pressure. We investigate after lung surgery the determinants of the esophageal and intrathoracic pressures and their differences. The esophageal pressure (through esophageal balloon) and the intrathoracic/pleural pressure (through the chest tube on the surgery side) were measured after surgery in 28 patients immediately after lobectomy or wedge resection. Measurements were made in the nondependent lateral position (without or with ventilation of the operated lung) and in the supine position. In the lateral position with the nondependent lung, collapsed or ventilated, the differences between esophageal and pleural pressure amounted to 4.4 ± 1.6 and 5.1 ± 1.7 cmH2O. In the supine position, the difference amounted to 7.3 ± 2.8 cmH2O. In the supine position, the estimated compressive forces on the mediastinum were 10.5 ± 3.1 cmH2O and on the iso-gravitational pleural plane 3.2 ± 1.8 cmH2O. A simple model describing the roles of chest, lung, and pneumothorax volume matching on the pleural pressure genesis was developed; modeled pleural pressure = 1.0057 × measured pleural pressure + 0.6592 ( r2 = 0.8). Whatever the position and the ventilator settings, the esophageal pressure changed in a 1:1 ratio with the changes in pleural pressure. Consequently, chest wall elastance (Ecw) measured by intrathoracic (Ecw = ΔPpl/tidal volume) or esophageal pressure (Ecw = ΔPes/tidal volume) was identical in all the positions we tested. We conclude that esophageal and pleural pressures may be largely different depending on body position (gravitational forces) and lung-chest wall volume matching. Their changes, however, are identical.

NEW & NOTEWORTHY Esophageal and pleural pressure changes occur at a 1:1 ratio, fully justifying the use of esophageal pressure to compute the chest wall elastance and the changes in pleural pressure and in lung stress. The absolute value of esophageal and pleural pressures may be largely different, depending on the body position (gravitational forces) and the lung-chest wall volume matching. Therefore, the absolute value of esophageal pressure should not be used as a surrogate of pleural pressure.
The effects of forearm position and contraction intensity on cortical and spinal excitability during a submaximal force steadiness task of the elbow flexors
Authors: Yacyshyn Alexandra F. , Kuzyk Samantha , Jakobi Jennifer M. , McNeil Chris J.
Published: November 2019

Elbow flexor force steadiness is less with the forearm pronated (PRO) compared with neutral (NEU) or supinated (SUP) and may relate to neural excitability. Although not tested in a force steadiness paradigm, lower spinal and cortical excitability was observed separately for biceps brachii in PRO, possibly dependent on contractile status at the time of assessment. This study aimed to investigate position-dependent changes in force steadiness as well as spinal and cortical excitability at a variety of contraction intensities. Thirteen males (26 ± 7 yr; means ± SD) performed three blocks (PRO, NEU, and SUP) of 24 brief (~6 s) isometric elbow flexor contractions (5, 10, 25 or 50% of maximal force). During each contraction, transcranial magnetic stimulation or transmastoid stimulation was delivered to elicit a motor-evoked potential (MEP) or cervicomedullary motor-evoked potential (CMEP), respectively. Force steadiness was lower in PRO compared with NEU and SUP ( P ≤ 0.001), with no difference between NEU and SUP. Similarly, spinal excitability (CMEP/maximal M wave) was lower in PRO than NEU (25 and 50% maximal force; P ≤ 0.010) and SUP (all force levels; P ≤ 0.004), with no difference between NEU and SUP. Cortical excitability (MEP/CMEP) did not change with forearm position ( P = 0.055); however, a priori post hoc testing for position showed excitability was 39.8 ± 38.3% lower for PRO than NEU at 25% maximal force ( P = 0.006). The data suggest that contraction intensity influences the effect of forearm position on neural excitability and that reduced spinal and, to a lesser extent, cortical excitability could contribute to lower force steadiness in PRO compared with NEU and SUP.

NEW & NOTEWORTHY To address conflicting reports about the effect of forearm position on spinal and cortical excitability of the elbow flexors, we examine the influence of contraction intensity. For the first time, excitability data are considered in a force steadiness context. Motoneuronal excitability is lowest in pronation and this disparity increases with contraction intensity. Cortical excitability exhibits a similar pattern from 5 to 25% of maximal force. Lower corticospinal excitability likely contributes to relatively poor force steadiness in pronation.
Experimental Study on Normal Frost-Heave Force Generated from Loess upon Freezing considering Multiple Factors
Authors: Zhao Zai-kun , Wang Tie-hang , Jin Xin , Zhang Yu
Published: November 2019

An experimental study on the normal frost-heave force generated by loess was conducted by subjecting loess with various water contents and densities to different temperature conditions. The experimental results show that the interaction of the three factors has a significant effect on the normal frost-heaving force. Normal frost-heave force increases exponentially with an increase in dry density and linearly with a reduction in the freezing temperature or an increase in water content; of these factors, dry density has the greatest influence on frost-heave force, followed by water content then temperature. A frost-heave force model is developed that includes overall consideration of the interactions of water content, density, and temperature based on fitting of the test results. The value calculated with the model is in good agreement with values measured in verification tests, indicating that the model has high accuracy and can provide scientific guidance for engineering design in loess areas.
A Rare Case of Breast Implant-Associated Diffuse Large B-Cell Lymphoma
Authors: Larrimore Christopher , Jaghab Annmarie
Published: November 2019

This is a case of an elderly female who presented for follow-up ultrasound of the right breast after routine mammogram revealed a small benign mass. A subsequent ultrasound detected a small nodular mass that was described as benign in appearance. Although the patient was asymptomatic, a fine-needle biopsy was performed to rule out malignancy. Results from immunohistochemistry and FISH studies of the biopsy were positive for diffuse large B-cell lymphoma (DLBCL). The patient underwent surgery for lumpectomy and removal of breast implants. Intraoperative tissue samples were analyzed by pathology using both flow cytometry and microscopy, and results confirmed DLBCL. With total tumor resection and implant removal completed, the patient did not require additional treatments as the prognosis of DLBCL status post implant removal is excellent. She returned for follow-up six months later and has since had no signs of reoccurrence.
Synthesis and Characterization of CeGdZn-Ferrite Nanoparticles as Magnetic Hyperthermia Application Agents
Authors: Hayek Saleh S.
Published: November 2019

This study focuses on the synthesis and characterization of a magnetic nanomaterial used in magnetic hyperthermia. Cerium gadolinium zinc-iron (CeGdZnFe) magnetic nanoparticles were synthesized by a coprecipitation method for application as magnetic hyperthermia agents. Determination of phase purity and their identification was achieved by X-ray diffraction studies using a Phillips powder diffractometer with Cu Kα radiation. Typical TEM micrographs of the dispersion of CeGdZn-ferrite nanoparticles and CeGdZn-ferrite PEG-encapsulated nanoparticles in ethanol deposited over a Cu grid were taken as part of the characterization techniques to be used for newly developed materials. It was then fitted by a Gaussian distribution with mean diameter dm ±1.0 nm. The investigation of magnetic properties showed that adjusting, Gd and Zn contributes to the nanoparticles added to the adjustment of all magnetic properties of CeGdZnFe.
Palladium-Catalyzed C(sp3)-H Arylation of Benzo[b]thiophen-3(2H)-one 1,1-Dioxide
Authors: Liu Hailong , Li Wenjing , Fu Haiyan , Chen Hua , Li Ruixiang , Li Yu
Published: November 2019

A new concise synthesis route of 2-phenylbenzo[b]thiophen-3(2H)-one 1,1-dioxide from benzo[b]thiophen-3(2H)-one 1,1-dioxide was developed using palladium-catalyzed C(sp3)-H arylation. Compared with the traditional route, this protocol can effectively save many steps and combine with the current research hotspot, C(sp3)-H activation. Moreover, this catalytic system is easy to operate and a good yield can be achieved.
Design and Development of a Delta 3D Printer Using Salvaged E-Waste Materials
Authors: Simons Anthony , Avegnon Kossi L. M. , Addy Cyrus
Published: November 2019

The next phase of industrialization in the world is the use of 3D printing technology. Various 3D printing technologies are employed all over the world and for different purposes, from 3D printed houses to 3D printed food nutrients. Printer movement is achieved by carriages moving in a clearly defined X, Y, and Z orientation. The 3D printer has a lower work rate; subsequently, many printouts consume a lot of time due to their complexity. This paper elaborates on the design and development of a faster and fixed build platform 3D printer (Delta 3D printer) using locally available materials and e-waste. The Delta 3D printer movement is faster with a stable bed. Printer movement is achieved using three vertical axes placed 120° apart. Accuracy and speed are achieved with the use of NEMA 17 stepper motors to drive the various carriages on the vertical axes. Design calculations show that the least force delivered by the stepper motor is 1.73 N which exceeds 0.8334 N, the weight of the load to be carried. Furthermore, a stepper motor must turn 80 steps (rotational motion) in order to achieve 1 mm advance (linear motion). This ensures a higher printout resolution. In place of traditional linear rails, locally sourced square pipes were adopted coupled with bearings and a 3D printed carriage support, and a relatively cheaper but stable linear rail was developed. The goal of this research was to develop an alternative easy-to-build Delta 3D printer using locally sourced materials. This goal of this research was achieved, and the developed prototype was test-run under load conditions. It is recommended that salvaged e-waste should be properly managed for easy acquisition.
Fourier Series Analysis for Novel Spatiotemporal Pulse Waves: Normal, Taut, and Slippery Pulse Images
Authors: Peng Bo , Luo Ching-Hsing , Sinha Nilotpal , Tai Cheng-Chi , Xie Xiaohua , Xie Haiqing
Published: November 2019

In this article, a three-dimensional pulse image (3DPI) instead of a one-dimensional temporal pulse wave is studied to elucidate its spatiotemporal characteristics. To check the spatial and temporal properties of 3DPI, adopted is Fourier series, in which a ratio (r) is defined as one amplitude divided by the sum of the first three amplitudes of harmonics. A ratio sequence is constituted from 70 to 90 ratios in a heartbeat with 70–90 3DPIs by sampling. Twenty-four subjects (14 males and 10 females with age of 22.2 ± 3.7 years, 20.4 ± 1.4 BMI, and 112.1 ± 4.7 mmHg systolic blood pressure) are involved in this research. There are significant statistical differences in the groups of the normal, taut, and slippery 3DPIs by the first harmonic ratio average (r1¯) and ratio difference (Δr1) produced from the ratio sequence. The proposed method of this study gives us a novel viewpoint to clarify the spatiotemporal characteristics of pulse images, which can translate and quantize the pulse feeling in Chinese medicine texts.
Role of Resveratrol on Indoxyl Sulfate-Induced Endothelial Hyperpermeability via Aryl Hydrocarbon Receptor (AHR)/Src-Dependent Pathway
Authors: Assefa Eskedar Getachew , Yan Qiaoqiao , Gezahegn Siameregn Berhe , Salissou Maibouge Tanko Mahamane , He Shuiqing , Wu Nannan , Zuo Xuezhi , Ying Chenjiang
Published: November 2019

Resveratrol (RES), a dietary polyphenol compound, has been shown to possess health benefits due to its anti-inflammatory, antioxidative, and antiatherosclerosis properties. Tryptophan metabolite-derived indoxyl sulfate (IS) is identified as one of the uremic toxins and physiological endogenous ligand/activator of aryl hydrocarbon receptor (AHR), associated with atherosclerosis in chronic kidney disease (CKD) patients. Studies have shown that a high serum level of IS causes deleterious effects on health primarily by inducing oxidative stress and endothelial dysfunction. However, the precise mechanisms are still unclear. Here, we investigated the underlying mechanism of IS effect on endothelial permeability and the role of RES on IS-induced endothelial hyperpermeability via the AHR/Src-dependent pathway. Bovine aorta endothelial cells (BAECs) were cultured and incubated with IS in the presence or absence of RES, and transendothelial electrical resistance (TEER) and permeability of cells were measured. Alongside, AHR, Src kinase, and Vascular Endothelial Cadherin (VE-Cadherin) activation were examined. Our data showed that IS reduced TEER of cells resulting in increased permeability. VE-Cadherin, a vital regulator of endothelial permeability, was also significantly activated in response to IS, which appeared to be associated with changes of endothelial permeability and AHR/Src kinase. Interestingly, in this setting, RES reversed the effect of IS and inhibited the increased activation of Src induced by IS-activated AHR and modulated VE-Cadherin and permeability. CH223191, an inhibitor of AHR, significantly inhibits IS-induced endothelial hyperpermeability. Further analysis with treatment of PP2, an inhibitor of Src abolishing Src activation, suggests downstream factors. All our data indicated that IS upregulated the AHR/Src kinase pathway, and increased endothelial permeability and phosphorylation of VE-Cadherin may be represented and provide new strategies for addressing protective properties of RES against Src kinase involved in AHR-mediated endothelial hyperpermeability. The findings may be crucial for managing diseases in which endothelial permeability is compromised, and the dietary polyphenols are involved.
BTBD7 Downregulates E-Cadherin and Promotes Epithelial-Mesenchymal Transition in Lung Cancer
Authors: Shu Jie , Wang Lin , Han Fei , Chen Yubin , Wang Shunjun , Luo Fanyan
Published: November 2019

Metastasis is the leading cause of lung cancer-associated death. Downregulated expression of E-cadherin followed by epithelial-mesenchymal transition (EMT) is critical for metastasis initiation in lung cancer. BTBD7 plays essential roles in lung cancer metastasis, but the mechanisms remain unknown. This study aimed to investigate the relationship between BTBD7 and E-cadherin in lung cancer and explore the role of BTBD7 in EMT. Fresh lung cancer and paracancer tissue specimens were collected from 30 patients, and the expression of BTBD7, E-cadherin, N-cadherin, fibronectin, and vimentin was analyzed by qRT-PCR, western blotting, and immunohistochemistry. A549 and HBE cells were cultured and treated with TGF-β1 for 72 h to induce EMT. Western blotting and qRT-PCR were performed to evaluate the expression of BTBD7, E-cadherin, N-cadherin, fibronectin, and vimentin. Then, A549 cells were treated separately with the BTBD7-ENTER plasmid, BTBD7-siRNA, and paclitaxel. After TGF-β1-induced EMT, the abovementioned markers were analyzed by western blotting and qRT-PCR. Wound healing assays were applied to assess the migration ability of cells in different groups. For animal experiments, A549 cells transfected with the BTBD7-ENTER plasmid were transplanted into BALB/c nude mice. After 4 weeks, all nude mice were sacrificed, and tumor tissues were harvested for qRT-PCR, western blot, and immunohistochemical analyses of the abovementioned markers. All experimental results showed that the levels of BTBD7, N-cadherin, fibronectin, and vimentin were increased in lung cancer tissues and cells, while the E-cadherin level was decreased. Transfection experiments showed that BTBD7 inhibited E-cadherin expression and enhanced EMT. Moreover, the migration capacity of lung cancer cells was increased by the high level of BTBD7. We concluded that BTBD7 is highly expressed during lung cancer development and metastasis and can inhibit the expression of E-cadherin and promote EMT in lung cancer. BTBD7 may thus be a therapeutic target for lung cancer.
Evaluating a Semiautonomous Brain-Computer Interface Based on Conformal Geometric Algebra and Artificial Vision
Authors: Ramírez-Moreno Mauricio Adolfo , Gutiérrez David
Published: November 2019

In this paper, we evaluate a semiautonomous brain-computer interface (BCI) for manipulation tasks. In such a system, the user controls a robotic arm through motor imagery commands. In traditional process-control BCI systems, the user has to provide those commands continuously in order to manipulate the effector of the robot step-by-step, which results in a tiresome process for simple tasks such as pick and replace an item from a surface. Here, we take a semiautonomous approach based on a conformal geometric algebra model that solves the inverse kinematics of the robot on the fly, and then the user only has to decide on the start of the movement and the final position of the effector (goal-selection approach). Under these conditions, we implemented pick-and-place tasks with a disk as an item and two target areas placed on the table at arbitrary positions. An artificial vision (AV) algorithm was used to obtain the positions of the items expressed in the robot frame through images captured with a webcam. Then, the AV algorithm is integrated into the inverse kinematics model to perform the manipulation tasks. As proof-of-concept, different users were trained to control the pick-and-place tasks through the process-control and semiautonomous goal-selection approaches so that the performance of both schemes could be compared. Our results show the superiority in performance of the semiautonomous approach as well as evidence of less mental fatigue with it.
Gain-of-Function Mutant p53 R273H Interacts with Replicating DNA and PARP1 in Breast Cancer
Authors: Xiao Gu , Lundine Devon , Annor George K. , Canar Jorge , Ellison Viola , Polotskaia Alla , Donabedian Patrick L. , Reiner Thomas , Khramtsova Galina F. , Olopade Olufunmilayo I. , Mazo Alexander , Bargonetti Jill
Published: November 2019

Over 80% of triple-negative breast cancers (TNBC) express mutant p53 (mtp53) and some contain oncogenic gain-of-function (GOF) p53. We previously reported that GOF mtp53 R273H upregulates the chromatin association of mini chromosome maintenance (MCM) proteins MCM2-7 and PARP and named this the mtp53–PARP–MCM axis. In this study, we dissected the function and association between mtp53 and PARP using a number of different cell lines, patient-derived xenografts (PDX), tissue microarrays (TMA), and The Cancer Genome Atlas (TCGA) database. Endogenous mtp53 R273H and exogenously expressed R273H and R248W bound to nascent 5-ethynyl-2´-deoxyuridine-labeled replicating DNA. Increased mtp53 R273H enhanced the association of mtp53 and PARP on replicating DNA. Blocking poly-ADP-ribose gylcohydrolase also enhanced this association. Moreover, mtp53 R273H expression enhanced overall MCM2 levels, promoted cell proliferation, and improved the synergistic cytotoxicity of treatment with the alkylating agent temozolomide in combination with the PARP inhibitor (PARPi) talazoparib. Staining of p53 and PARP1 in breast cancer TMAs and comparison with the TCGA database indicated a higher double-positive signal in basal-like breast cancer than in luminal A or luminal B subtypes. Higher PARP1 protein levels and PAR proteins were detected in mtp53 R273H than in wild-type p53-expressing PDX samples. These results indicate that mtp53 R273H and PARP1 interact with replicating DNA and should be considered as dual biomarkers for identifying breast cancers that may respond to combination PARPi treatments.

Significance:

p53 gain-of-function mutant 273H and PARP1 interact with replication forks and could serve as potential biomarkers for breast cancer sensitivity to PARP inhibitors.
Transcriptional Profiles and Stromal Changes Reveal Bone Marrow Adaptation to Early Breast Cancer in Association with Deregulated Circulating microRNAs
Authors: Chiodoni Claudia , Cancila Valeria , Renzi Tiziana A. , Perrone Milena , Tomirotti Andrea M. , Sangaletti Sabina , Botti Laura , Dugo Matteo , Milani Matteo , Bongiovanni Lucia , Marrale Maurizio , Tripodo Claudio , Colombo Mario P.
Published: November 2019

The presence of a growing tumor establishes a chronic state of inflammation that acts locally and systemically. Bone marrow responds to stress signals by expanding myeloid cells endowed with immunosuppressive functions, further fostering tumor growth and dissemination. How early in transformation the cross-talk with the bone marrow begins and becomes detectable in blood is unknown. Here, gene expression profiling of the bone marrow along disease progression in a spontaneous model of mammary carcinogenesis demonstrates that transcriptional modifications in the hematopoietic compartment occurred as early as preinvasive disease stages. The transcriptional profile showed downregulation of adaptive immunity and induction of programs related to innate immunity and response to danger signals triggered by activating transcription factor 3. Transcriptional reprogramming was paralleled by the expansion of myeloid populations at the expense of erythroid and B lymphoid fractions. Hematopoietic changes were associated with modifications of the bone marrow stromal architecture through relocalization and increased density in the interstitial area of Nestin+ mesenchymal cells expressing CXCL12 and myeloid cells expressing CXCL12 receptor CXCR4. These early events were concomitant with deregulation of circulating miRNAs, which were predicted regulators of transcripts downregulated in the bone marrow and involved in lymphoid differentiation and activation. These data provide a link between sensing of peripheral cancer initiation by the bone marrow and hematopoietic adaptation to distant noxia through transcriptional rewiring toward innate/inflammatory response programs.

Significance:

The bone marrow senses distant tissue transformation at premalignant/preinvasive stages, suggesting that circulating messengers, intercepted in the blood, could serve as early diagnostic markers.
Serous Retinal Detachment in Dome-Shaped Macula Is Associated with Greater Central Choroidal Blood Flow Measured by Optical Coherence Tomography Angiography
Authors: Soudier Guillaume , Gaudric Alain , Gualino Vincent , Tadayoni Ramin , Speeg-Schatz Claude , Liu Xuanli , Gaucher David
Published: November 2019

Purpose: Dome-shaped macula (DSM) is characterized by an inward bulge in the macula, often associated with a myopic staphyloma. One complication of DSM is particularly studied: foveolar serous retinal detachment (SRD). This study analyzed the variations of optical coherence tomography angiography (OCT-A) decorrelation signal in cases of DSM with and without SRD. Methods: This was a retrospective study including twenty height eyes presenting with DSM. OCT-A scans were recorded, and the intensity of the choroidal decorrelation signal was quantified to analyze choroidal blood flow (CBF) in central, temporal, and nasal macular areas. The size of retinal pigment epithelium (RPE) atrophy was evaluated. Results: CBF in the central area was significantly greater in the SRD group than in the no-SRD group (7.00 × 105 vs. 2.58 × 105) (p = 0.0049). CBF appeared decreased in the subfoveal area compared with the periphery for patients without SRD (p = 0.0107). The size of RPE atrophy was 0.762 optic disc area ±0.87. RPE atrophy correlated very significantly with CBF (p = 0.0012). Conclusion: A greater retrofoveolar CBF intensity is associated with the presence of SRD. These changes could reflect variations of CBF, and may represent a potential explanation for the pathogenesis of SRD in DSM.
Effects of Dentifrices Differing in Fluoride Content on Remineralization Characteristics of Dentin in vitro
Authors: Wierichs Richard J. , Rupp Katharina , Meyer-Lueckel Hendrik , Apel Christian , Esteves-Oliveira Marcella
Published: November 2019

Objectives: The aim of this study was to compare the caries preventive effect of highly fluoridated dentifrices and gels on sound dentin as well as on artificial dentin caries-like lesions. Methods: Bovine dentin specimens (n = 240), with 2 different surfaces each (1 sound surface [sound treatment (ST)] and one caries lesion [demineralized treatment (DT)]), were prepared and randomly allocated to one highly (6 × 120 min demineralization/day [H]) and one lowly cariogenic (6 × 60 min demineralization/day [L]) pH-cycling model. Treatments during pH-cycling (28 days) were: brushing 2×/day with: 0 ppm F [H0/L0], 1,450 ppm F [H1,450/L1,450], 2,800 ppm F [H2,800/L2,800], 5,000 ppm F [H5,000/L5,000], 5,000 ppm F plus TCP [H5,000+TCP/L5,000+TCP], and 12,500 ppm F [H12,500/L12,500] containing dentifrices/gels. Dentifrice/gel slurries were prepared with deionized water (1:2 wt/wt). Differences in integrated mineral loss (∆∆Z) and ∆ lesion depth were calculated between values before and after pH-cycling using transversal microradiography. Results: The correlation between ΔΔZDT and F– was strong for the highly (rH = 0.691; p < 0.001) and moderate (rL = 0.500; p < 0.001) for the lowly cariogenic model, indicating a fluoride dose-response for both. Significant differences for ΔΔZDT and ΔΔZST could be found between H0, H1,450, H5,000, and H12,500 as well as L0, L5,000, and L125,000 (p ≤ 0.046; analysis of covariance [ANCOVA]). Except for 0 ppm F–, no significant difference in ΔΔZST and ΔΔZDT could be found between the highly and lowly cariogenic model (p ≥ 0.056; ANCOVA). Conclusion: For both pH-cycling conditions a dose-response for fluoride could be revealed. For elderly people with exposed root surfaces, the use of gels containing 12,500 ppm F instead of regularly (1,450 ppm F) or highly (5,000 ppm F) fluoridated dentifrices should be further investigated, as it offered higher caries-preventive effects in vitro.
Isolated Breast Relapse after Metastatic Alveolar Rhabdomyosarcoma in a Young Premenarcheal Girl: What Could Have Been Done?
Authors: Haddad Raymond N. , Ghattas Souad , Torbey Paul-Henri
Published: November 2019

Alveolar rhabdomyosarcoma (RMS) is one of the most common pediatric soft-tissue neoplasms. Breast involvement either as primary tumor or metastasis is extremely rare. Herein, we report a case of primary limb alveolar RMS with breast metastases in a young premenarcheal girl that relapsed only to the metastatic breast site after achieving complete response. Accordingly, we believe that investigations of the mammary glands should be part of the routine diagnostic workup in adolescent females with RMS. Local therapeutic measures to control breast disease, including surgery or radiotherapy has to be considered for better prognosis. Newer radiation modalities aiming at reducing side effects should be developed.
Surgical Management of Non-Malignant Esophageal Perforations: A Single-Center Analysis Over a 15-Year Period
Authors: Karstens Karl-Frederick , Bellon Eugen , Tachezy Michael , Izbicki Jakob R. , Ghadban Tarik , Duprée Anna , Uzunoglu Faik G. , Bachmann Kai , Koenig Alexandra , Reeh Matthias
Published: November 2019

Purpose: Esophageal perforations are associated with high morbidity and mortality. Different nonoperative and operative treatment options have been proposed. This study focuses on the impact of different surgical treatments in nonmalignant esophageal perforations and tries to identify predictors of mortality in a single tertiary center over a 15-year period. Methods: From 2002 to 2017, patients with surgically managed esophageal perforation were identified from our database. Patients with esophageal malignancies were excluded. Etiology, clinical data, treatment, and outcome were analyzed. A multivariate logistic regression analysis was performed to investigate the impact on mortality. Results: A total of 72 patients were identified. The majority of perforations were iatrogenic (54.2%) followed by Boerhaave’s syndrome (23.6%). Most ruptures were found in the distal third of the esophagus (59.7%) measuring <3 cm (61.1%). Patients were treated with exploration and drainage (8.3%), primary suture and patch reinforcement (36.1%), resection and restoration of continuity (25.0%), or resection without restoration of continuity (30.6%). Delayed therapy significantly correlated with sepsis (p < 0.0001) and mortality (p = 0.032). A correlation between an increasing perforation length with sepsis (p = 0.012) was observed. A higher Perforation Severity Score (PSS; OR 4.430; 95% CI 1.143–17.174; p = 0.031) and a higher American Society of Anesthesiologists (ASA) score (OR 2.923; 95% CI 1.011–8.448; p = 0.048) were associated with mortality in multivariate analysis. Conclusion: Esophageal perforations are associated with high mortality, and larger ruptures are associated with worse outcome. Rapid diagnosis and treatment are crucial for patient survival. Hence, PSS and ASA score help to identify high-risk patients. The advantage of surgical management lies in the rapid control of the septic focus in an already critically ill patient. Though, the kind of surgical technique needs to be adjusted to the individual situation.
Gallstone Disease is an Independent Predictor for Poststroke Cognitive Impairment in Young Patients with Acute Ischemic Stroke
Authors: Weng Xiongpeng , Fu Fangwang , Ling Yi , Sun Jing , Chen Weilai
Published: November 2019

Background: Poststroke cognitive impairment (PCI) is an important public health issue. Previous studies proved that gallstone disease (GD) was a predictor for cardiovascular and cerebrovascular disease. However, association between PCI and GD remains unclear. We aimed to investigate the predictive value of GD on cognitive impairment after acute ischemic stroke (AIS). Methods: We recruited 373 AIS patients, and the information on patient demographics and risk factors was collected. Cognitive function would be assessed 3-month after AIS. They would undergo gallbladder ultrasonographic examination and structured assessment during hospitalization. Patients were divided into young group (age <65 years) and elder group (age ≥65 years). Multivariate logistic regression models were used to identify the predictors of PCI. Results: PCI was identified in 176 (47.18%) AIS patients. Independent predictors of PCI were GD (p = 0.014), the National Institutes of Health Stroke Scale score and age. While carotid plaque (p = 0.058) seemed like a potential risk factor for PCI. In young group, GD (p = 0.027) was associated to PCI, in elder group, carotid plaque (p = 0.006), and age (p = 0.033) were significantly correlated to PCI. Conclusion: GD was an age-dependent predictor for PCI, particularly in the young AIS patients. Therefore, AIS patients with GD, especially the young, should be systematically evaluated for cognitive function.
Blood Pressure Variability and Cerebral Small Vessel Disease
Authors: Ma Yuan , Song Alex , Viswanathan Anand , Blacker Deborah , Vernooij Meike W. , Hofman Albert , Papatheodorou Stefania
Published: November 2019

Background and Purpose—

Blood pressure (BP) variability may increase the risk of stroke and dementia. It remains inconclusive whether BP variability is associated with cerebral small vessel disease, a common and potentially devastating subclinical disease that contributes significantly to both stroke and dementia.

Methods—

A systematic review and meta-analysis of prospective cohort studies that examined the association between BP variability and the presence or progression of established markers of cerebral small vessel disease, including white matter hyperintensities, lacunes, and microbleeds on magnetic resonance imaging. We searched MEDLINE, EMBASE, and Web of Science. Ten studies met the criteria for qualitative synthesis and 7 could be included in the meta-analysis. Data were synthetized using random-effect models.

Results—

These studies included a total of 2796 individuals aged 74 (mean) ±4 (SD) years, with a median follow-up of 4.0 years. A one SD increase in systolic BP variability was associated with increased odds of the presence or progression of white matter hyperintensities (odds ratio, 1.26 [95% CI, 1.06–1.50]). The association of systolic BP variability with the presence of lacunes (odds ratio, 0.93 [95% CI, 0.74–1.16]) and the presence of microbleeds (odds ratio, 1.13 [95% CI, 0.89–1.44]) were not statistically significant.

Conclusions—

A larger BP variability may be associated with a higher risk of having a higher burden of white matter hyperintensities. Targeting large BP variability has the potential to prevent cerebral small vessel disease and thereby reducing the risk of stroke and dementia. The potential issue of reverse causation and the heterogeneity in the assessment of cerebral small vessel disease markers should be better addressed in future studies.
The Frightful Hobgoblin against Empire
Authors: Drapeau Thierry
Published: November 2019

Karl Marx and the Chartist leader, writer and poet Ernest Jones developed a close intellectual and political partnership from the late 1840s through the late 1850s. Their friendship invites attention because it places Marx in the company of one of Chartism’s leading anti-colonial advocates, precisely at a time when he was simultaneously moving in that direction. This article explores the ways in which Marx and Jones converged in their estimation of the 1857 Indian uprising. It is argued that the shift in Marx’s thought, whereby the dialectics of colonialism and anti-colonialism are integrated within his materialist conception of history, was not independent of Jones’s influence.
Discordia, Concordia
Authors: Disselkamp Martin
Published: November 2019

Der Aufsatz untersucht, auf welche Weise sich frühneuzeitliche Türkenkriegsprojekte mit politischen Dissoziationserfahrungen auseinandersetzen. Auf der einen Seite entfalten solche Projekte das Bild eines politisch zersplitterten Europa, in dem ein allgemeines Interessendenken auf den Spuren von Machiavelli um sich gegriffen hat. Auf der anderen Seite muß jeder Aufruf, der türkischen Bedrohung massiv entgegenzutreten, die Frage berücksichtigen, wie die ‘discordierenden’ Staaten oder das zerstrittene deutsche Reich auf eine gemeinsame Operation verpflichtet werden können. Türkenkriegsprojekte liefem deshalb auch utopische Einigkeitsbilder mit unterschiedlichen Schwerpunkten, die schließlich die ‘Zwietracht’ heroisch überbieten wollen.
Neues vom alten Ernst Schwabe von der Heyde
Authors: Aurnhammer Achim
Published: November 2019

Martin Opitz zählte Ernst Schwabe von der Heyde zu seinen wichtigsten Vorbildern. Gleichwohl machte er mit nur wenigen Dichtungen Schwabes bekannt. Der glückliche Fund von drei unbemerkt gebliebenen Alexandrinersonetten, die anläßlich der Krönung von Kaiser Matthias im Jahre 1612 entstanden sind, erweitert unsere Kenntnisse über Schwabes dichterisches Werk und eröffnet neue Einblicke in die voropitzische Modernisierung der deutschen Literatur.
Leibniz-Rezeption uno Leibniz-Übersetzung im 18. Jahrhundert
Authors: Till Dietmar
Published: November 2019

Die Abhandlung untersucht die deutschen Übersetzungen der Théodicée (1710) und der Monadologie (1714) von Gottfried Wilhelm Leibniz. Dabei zeigt sich, daß es einen engen Zusammenhang zwischen der impliziten Übersetzungstheorie der jeweiligen Übersetzer und Christian Wolffs Programm einer deutschen Wissenschaftssprache gibt. Der Aufsatz zeigt am Beispiel der philosophischen Fachterminologie, wie die Übersetzer dieses Wissenschaftssprachprogramm in unterschiedlicher Weise realisieren. Der Begriff der ‘Leibniz-Wolffschen-Schulphilosophie’ gewinnt vor diesem Hintergrund neue Plausibilität: Leibniz wird von den ‘Wolffianischen’ Übersetzem als ein Autor konstruiert, der Leibniz auch philosophisch nahesteht. Die fachsprachliche Übersetzungspraxis spielt dabei eine zentrale Rolle.
Ancient DNA Analysis of the Thulamela Remains: Deciphering the Migratory Patterns of a Southern African Population
Authors: Bodiba Molebogeng , Steyn Maryna , Bloomer Paulette , Mosothwane Morongwa N. , Rühli Frank , Bouwman Abigail
Published: November 2019

Ancient DNA (aDNA) analysis was employed to obtain information on the population relationships of the two Thulamela individuals (AD 1400-1700) and six other skeletons from various archaeological sites of the southern African Iron Age – Tuli (Botswana), Nwanetsi, Makgope, Happy Rest and Stayt. Although sequences were short, it seems that the Thulamela female aligns somewhat more with eastern populations as opposed to the male who aligns more with western groups. This result is not surprising given that the two individuals were buried at the same site but their burials were hundreds of years apart. It was also possible to identify genetic links between the Iron Age individuals and modern southern African populations (e.g. some of the skeletons assessed showed maternal genetic similarities to present-day Sotho/Tswana groups) and to separate the samples into at least two genetic groups. Poor quality and quantity of DNA meant that only haplogroups, not subhaplogroups, of the individuals could be traced.