bluuebunny/crossref_metadata_2025 huggingface dataset:
Characterization of Host Responses during Pseudomonas aeruginosa Acute Infection in the Lungs and Blood and after Treatment with the Synthetic Immunomodulatory Peptide IDR-1002
Authors: Wuerth Kelli , Lee Amy H. Y. , Falsafi Reza , Gill Erin E. , Hancock Robert E. W.
Published: October 2018

Pseudomonas aeruginosa
is an opportunistic pathogen that causes nosocomial pneumonia and infects patients with cystic fibrosis.
P. aeruginosa
lung infections are difficult to treat due to bacterial resistance to antibiotics, and strains with multidrug resistance are becoming more prevalent.
Diffusely AdherentEscherichia coliStrains Isolated from Healthy Carriers Suppress Cytokine Secretions of Epithelial Cells Stimulated by Inflammatory Substances
Authors: Tanimoto Yoshihiko , Tamai Sayaka , Matsuzaki Takehiro , Takeuchi Narumi , Noju Takumi , Yanagida Saki , Kage-Nakadai Eriko , Yamaguchi Yoshihiro , Kodama Toshio , Nakamura Shota , Motooka Daisuke , Iida Tetsuya , Nishikawa Yoshikazu
Published: October 2018

Diarrheagenicity of diffusely adherentEscherichia coli(DAEC) remains controversial. Previously, we found that motile DAEC strains isolated from diarrheal patients induced high levels of interleukin 8 (IL-8) secretion via Toll-like receptor 5 (TLR5).
Hb Palencia: a novel δβδ-type two-way fusion variant with β-globin-like expression levels
Authors: Nieto Jorge M , González Fernando Ataúlfo , Alonso José María , Golvano Eva , Guerrero Lucia , Albarrán Beatriz , villegas Ana , Martínez Rafael B , Ropero Paloma
Published: October 2018

Aims

Fusion proteins of unequal recombination events at the β-globin locus have pathological effect. The haemoglobin (Hb) variants of type Lepore are fusion proteins characterised by β-like globin chains with a δ-globin (HBD) N-terminus and a β-globin (HBB) C-terminus, whereas reciprocal products of underlying crossover events hold aHBBN-terminus andHBDC-terminus instead. Finally, Hb Parchman contains a β-like globin chain with a centralHBBfragment andHBD-derived N-termini and C-termini, whereas reciprocal hybrid proteins are as yet unknown.

Methods

The propositus was an 80-year-old Caucasian man, whose HbA1c quantification by HPLC (Variant II turbo) for exclusion of type-2 diabetes revealed an abnormal peak. Haemoglobins were analysed by ion-exchange HPLC (Variant II) and capillary electrophoresis (Sebia Capillarys Flex) and DNA by automatic Sanger sequencing of δ-globin and β-globin genes.

Results

Sequencing showed anHBB-HBD-HBBhybrid gene, withHBD-derived central codons 9–31, andHBB-derived UTRs and complementary coding regions. The corresponding new hybrid haemoglobin (Hb Palencia) is represented at ≈40%, similar to HbA.

Conclusion

Hb Palencia contains the first globin variant with internalHBDsequences andHBB-derived N-terminal and C-terminal and regulatory sequences. Relative quantity of the new βδβ-type variant suggests transcriptional control byHBBelements and a half-life similar to normalHBB.
Axis dorsal laminotomy in dogs: a retrospective analysis of 10 cases
Authors: Barker David Anthony , Palus Viktor , Eminaga Salih , Cherubini Giunio Bruto
Published: October 2018

The aims of this study were to describe the surgical procedure, and procedure‐related postoperative outcomes after dorsal axis laminotomy. Ten client‐owned dogs with neurological signs due to pathology within the vertebral canal at the level of the axis were reviewed (2009–2018). Patients underwent dorsal laminotomy using a modification of the originally described technique. The axis dorsal lamina was repositioned and secured using absorbable suture material. Eight dogs had improved neurological function; one dog had static function while one dog was euthanased secondary to proposed persistence of the primary myelopathy. Postoperative radiographs confirmed maintained anatomic reduction and early bone healing in two dogs, one‐year postoperative radiographs and one‐month and two‐year postoperative CT confirmed osteosynthesis in one dog each. Medium/long‐term (4–82 months) follow‐up was reported in seven dogs. Mortality in this case series was 10 per cent. Delayed union of the laminotomy flap is a complication associated with this technique.
Presumptive malignant nerve sheath tumour affecting the cauda equina and caudal nerves of a dog
Authors: Lourinho Filipa , Trevail Raquel , Craig Andrew , Carrera Ines
Published: October 2018

A 13‐year‐old, male, entire cocker spaniel was presented with a history of progressive discomfort during defecation. The referring veterinary surgeon suspected anal sacculitis and treated accordingly; however, this was unsuccessful, and the dog was referred for further investigations. Examination revealed marked resentment to manipulation of the tail but was otherwise unremarkable. Radiographs revealed lytic lesions in the first three caudal vertebrae, and MRI of the lumbosacral and first caudal nerves revealed severe enlargement of the caudal nerves within the vertebral canal with extension into the right ventral branches. These findings were highly suggestive of a nerve sheath tumour. Histological and immunohistochemical analysis of sampled tissues supported the suspected diagnosis. The dog was euthanised based on the guarded prognosis and perceived poor quality of life. This report describes an infrequent location for nerve sheath tumour with tail pain and discomfort during defecation as the only clinical manifestations.
The initial-boundary value problem for the Schrödinger–Korteweg–de Vries system on the half-line
Authors: Cavalcante Márcio , Corcho Adán J.
Published: October 2018

We prove local well-posedness for the initial-boundary value problem (IBVP) associated to the Schrödinger–Korteweg–de Vries system on right and left half-lines. The results are obtained in the low regularity setting by using two analytic families of boundary forcing operators, one of these families being developed by Holmer to study the IBVP associated to the Korteweg–de Vries equation [The initial-boundary value problem for the Korteweg–de Vries equation, Comm. Partial Differential Equations 31 (2006) 1151–1190] and the other one was recently introduced by Cavalcante [The initial-boundary value problem for some quadratic nonlinear Schrödinger equations on the half-line, Differential Integral Equations 30(7–8) (2017) 521–554] in the context of nonlinear Schrödinger with quadratic nonlinearities.
Hardy’s inequality in a limiting case on general bounded domains
Authors: Byeon Jaeyoung , Takahashi Futoshi
Published: October 2018

In this paper, we study Hardy’s inequality in a limiting case: [Formula: see text] for functions [Formula: see text], where [Formula: see text] is a bounded domain in [Formula: see text] with [Formula: see text]. We study the attainability of the best constant [Formula: see text] in several cases. We provide sufficient conditions that assure [Formula: see text] and [Formula: see text] is attained, here [Formula: see text] is the [Formula: see text]-dimensional ball with center the origin and radius [Formula: see text]. Also, we provide an example of [Formula: see text] such that [Formula: see text] and [Formula: see text] is not attained.
Existence and concentration of solutions for singularly perturbed doubly nonlocal elliptic equations
Authors: Lü Dengfeng , Peng Shuangjie
Published: October 2018

We consider the existence and concentration of positive solutions to a singularly perturbed doubly nonlocal elliptic equation [Formula: see text] where [Formula: see text] is a parameter, [Formula: see text] are constants, [Formula: see text] and [Formula: see text] is an external potential, [Formula: see text] and [Formula: see text]. Under some suitable assumptions on [Formula: see text] and [Formula: see text], by using the penalization method, we prove that for [Formula: see text] small enough there exists a family of positive solutions which concentrate on the local minimum points of the potential [Formula: see text] as [Formula: see text].
Multiplicity and concentration results for a class of critical fractional Schrödinger–Poisson systems via penalization method
Authors: Ambrosio Vincenzo
Published: October 2018

We deal with the multiplicity and concentration of positive solutions for the following fractional Schrödinger–Poisson-type system with critical growth: [Formula: see text] where [Formula: see text] is a small parameter, [Formula: see text], [Formula: see text], [Formula: see text], with [Formula: see text], is the fractional Laplacian operator, [Formula: see text] is a continuous positive potential and [Formula: see text] is a superlinear continuous function with subcritical growth. Using penalization techniques and Ljusternik–Schnirelmann theory, we investigate the relation between the number of positive solutions with the topology of the set where the potential attains its minimum value.
Modeling ion permeation in wild-type and mutant human α7 nachr ion channels
Authors: Kucukkal Tugba G , Alsaiari Feras , Stuart Steven J
Published: October 2018

Molecular dynamics simulations of wild type and two mutant (T248F and L251T) human [Formula: see text]7 nicotinic acetylcholine receptors (nAChR) have been performed. The channel transmembrane domains were modeled from the closed channel structure from torpedo ray (PDB ID 2BG9) and embedded in DPPC lipid bilayers, surrounded by physiological saline solution. An external electric field was used to obtain stable open channel structures. The adaptive biasing force (ABF) method was used to obtain potential of mean force (PMF) profiles for Na[Formula: see text] ion translocation through the wild type and mutant receptors. Based on the geometry and PMF profiles, the channel gate was found to be at one of the two hydrophobic conserved regions (V249-L251) near the lower end of the channel. The L251T mutation reduced the energetic barrier by 1.9[Formula: see text]kcal/mol, consistent with a slight increase in the channel radius in the bottleneck region. On the other hand, the T248F mutation caused a significant decrease in the channel radius (0.4 Å) and a substantial increase of 3.9[Formula: see text]kcal/mol in the energetic barrier. Ion permeation in all three structures was compared and found to be consistent with barrier height values. Using an external field in an incrementally increasing manner was found to be an effective way to obtain stable open, conducting channel structures.
Bioinformatic analysis of nucleotide cyclase functional centers and development of ACpred webserver
Authors: Xu Nuo , Zhang Changjiang , Lim Leng Leng , Wong Aloysius
Published: October 2018

Cyclic mononucleotides, in particular 3',5'-cyclic guanosine monophosphate (cGMP) and 3',5'-cyclic adenosine monophosphate (cAMP), are molecular signals that mediate a myriad of biological responses in organisms across the tree of life. In plants, they transduce signals such as hormones and peptides perceived at receptors on the cell surface into the cytoplasm to orchestrate a cascade of biochemical reactions that enable them to grow and develop, and adapt to light, hormones, salt and drought stresses as well as pathogens. However, their generating enzymes (guanylyl cyclases, GCs and adenylyl cyclases, ACs) have just been recently discovered and are still poorly understood. Here, we employed a computational approach to probe the physicochemical properties of the catalytic centers of these enzymes and the knowledge of which, was used to create a web-based tool, ACPred (http://gcpred.com/acpred) for the prediction of AC functional centers from amino acid sequence. Understanding the nature of such catalytic centers have enabled the creation of predictive tools such as ACPred which will in turn, facilitate the discovery of novel cellular components across different systems.
An effective sequence structure representation for long non-coding RNA identification and cancer association using machine learning methods
Authors: Madhavan Manu , Nair Gopakumar Gopalakrishnan
Published: October 2018

The invent of high-throughput technologies and consequent developments in Bioinformatics research unveiled many important non-coding transcript molecules such as Long non-coding RNAs (lncRNAs). The available studies confirmed that lncRNAs play important genetic and epigenetic roles in higher-order species like the human and their differential expressions leads to complex diseases like cancer. Even though there are arrays of studies and related tools for the analysis, less conserved patterns in the sequences and intractable structural properties challenge the understanding of varying functionalities of lncRNAs. For the better approximation of these characteristics, higher quality feature representation is required. This paper proposes an extended hybrid sequence-structure feature set for machine learning based lncRNA analysis. Here, the sequence features are derived from various frequencies of
k
-mer patterns, GC content and molecular weight. The structure representations consider the context of different secondary structure elements which include stems, interior loops, multi-loops and hairpin loops. These features are used for the classification of lncRNA/mRNA and cancerous/non-cancerous lncRNAs. The classifications use machine learning algorithms such as LDA based topic model, Random Forest, SVM and Naïve Bayes. The results show that the proposed feature set is effective in classifying lncRNAs and provide a direction towards the analysis of the role of secondary structure elements in cancer-related lncRNAs.
Cystic Fibrosis: Emerging Understanding and Therapies
Authors: Rey Michael M. , Bonk Michael P. , Hadjiliadis Denis
Published: October 2018

Cystic fibrosis (CF) is the most common life-limiting genetic disease in Caucasian patients. Continued advances have led to improved survival, and adults with CF now outnumber children. As our understanding of the disease improves, new therapies have emerged that improve the basic defect, enabling patient-specific treatment and improved outcomes. However, recurrent exacerbations continue to lead to morbidity and mortality, and new pathogens have been identified that may lead to worse outcomes. In addition, new complications, such as CF-related diabetes and increased risk of gastrointestinal cancers, are creating new challenges in management. For patients with end-stage disease, lung transplantation has remained one of the few treatment options, but challenges in identifying the most appropriate patients remain.
Aberrant Thyroid-Stimulating Hormone Receptor Signaling Increases VEGF-A and CXCL8 Secretion of Thyroid Cancer Cells, Contributing to Angiogenesis and Tumor Growth
Authors: Song Young Shin , Kim Min Joo , Sun Hyun Jin , Kim Hwan Hee , Shin Hyo Shik , Kim Young A. , Oh Byung-Chul , Cho Sun Wook , Park Young Joo
Published: October 2018

Purpose:

Thyroid-stimulating hormone (TSH) suppression is widely used to treat well-differentiated thyroid cancer, whereas its role in poorly differentiated thyroid cancer (PDTC) is undetermined. Besides thyrocytes, TSH also binds to stromal cells, comprising tumor microenvironments. This study aimed to investigate the effects of TSH on tumor microenvironments in PDTC.

Experimental Design:

An ectopic tumor model using PDTC cells (BHP10-3SCp and FRO), which exhibit TSH/cAMP-independent cell growth, was treated with TSH. IHC was performed using tissue microarrays from 13 PDTCs.

Results:

TSH treatment significantly enhanced tumor growth of PDTCs with increased vascularity but not that of breast cancer cells, suggesting this effect is unique to thyroid cancer cells, not stromal cells. TSH significantly upregulated VEGF-A and CXCL8 expressions in BHP10-3SCp cells via AKT and ERK signaling, resulting in higher concentrations of VEGF-A and CXCL8 in conditioned medium of TSH-treated BHP10-3SCp cells (TSH-CM) compared with controls. TSH-CM treatment enhanced tube formation potentials of endothelial cells, and blocking VEGF and/or CXCL8 reduced them. Blocking VEGF and/or CXCL8 also reduced TSH-dependent tumor growth with reduced tumor vasculature in vivo. TSH-treated tumors showed increased macrophage densities, and macrophage inhibition reduced TSH-dependent tumor growth in vivo. In human PDTCs, preoperative TSH levels were positively associated with VEGF-A and tumor size, and the expression of VEGF-A was positively correlated with CD31, CD163, and CXCL8, and their clinical poor prognosis.

Conclusions:

Aberrant TSH receptor signaling modulates tumor angiogenesis by stimulating VEGF-A and CXCL8 secretion from PDTC cells and enhances tumor growth; thus, TSH suppression is beneficial for treating PDTCs.
Clinical Impact of a Restrictive Labor Induction Approval Process
Authors: Tolcher Mary Catherine , Hokenstad Alexis N. , Weaver Amy L. , McGree Michaela E. , Rose Carl H. , Famuyide Abimbola O. , Brost Brian C.
Published: October 2018

Background/Aims: The aim of this study was to evaluate the impact of a restrictive labor induction approval process on induction and primary cesarean delivery rates. Methods: A retrospective cohort study was conducted at a tertiary care academic center from 2006 through 2012. The cohort of deliveries before (pre-intervention) and after (post-intervention) the process included term, singleton pregnancies with no contraindication to vaginal delivery. The primary outcome was induction of labor rates, subgrouped on the basis of whether it was medically or nonmedically indicated. Secondary outcomes included the primary cesarean rate and other maternal and neonatal outcomes. Results: Of 13,753 deliveries, 6,746 met study inclusion criteria. There was a significant decrease in induction rates comparing the pre- and post-intervention periods (21.0 vs. 18.5%, p = 0.01). Nonmedically indicated induction rates also decreased significantly (2.9 vs. 0.6%, p < 0.001). No difference was observed in medically indicated induction (18.1 vs. 17.9%, p = 0.84), the primary cesarean rate (14.4 vs. 15.8%, p = 0.12), or any of the measured neonatal outcomes (p > 0.05). Conclusions: Implementation of a labor induction approval process was associated with a significant reduction in overall and non-indicated induction rates but did not affect the primary cesarean rate or neonatal outcomes.
Single-Fraction Stereotactic Body Radiotherapy for Oligometastatic Lymph Node Relapse in Prostate Cancer
Authors: Loi Mauro , Di Cataldo Vanessa , Francolini Giulio , Bonomo Pierluigi , Masi Laura , Simontacchi Gabriele , Detti Beatrice , Greto Daniela , Desideri Isacco , Livi Lorenzo
Published: October 2018

Background: Stereotactic body radiotherapy (SBRT) emerged as a treatment option in oligometastatic (≤3 metastases) patients experiencing lymph node relapse from treated prostate cancer. No recommendations are available concerning dose schedule, and available studies report the use of multiple-fraction regimens due to theoretical lower toxicity and higher cumulative dose delivered to the target. The aim of the present study was to evaluate the safety and efficacy of a dose-intensive, single-fraction SBRT regimen. Patients and Methods: Retrospective data on outcome and toxicity from 27 treatments on 23 consecutive patients were collected. Statistical analysis was performed. Results: Median follow-up was 22 months (range 6-63, interquartile range 15-28). Biochemical progression-free survival (bPFS) at 6 months, 1 year, and 2 years were 65%, 40%, and 26%, respectively. In 2 cases acute toxicity of grade 1 were observed. Conclusion: Single-fraction SBRT for lymph node relapse of oligometastatic prostate cancer resulted in promising biochemical control with minimal toxicity.
Hematological Toxicity of Hypofractionated Radiotherapy: A Review of the Available Evidence
Authors: Spałek Mateusz , Wyrwicz Lucjan
Published: October 2018

Hypofractionated radiotherapy is commonly used to treat many cancers. The number of indications for this fractionation schedule is increasing. Knowledge of the potential hematological toxicity arising from hypofractionated irradiation is vital since many patients receive further systemic treatment. This review analyzes the available evidence on the effect of hypofractionated radiotherapy on hematological toxicity. However, radiobiological data on bone marrow responses to high doses of radiation per fraction are sparse. Additional biological effects may also play an significant role in bone marrow function and recovery after hypofractionated radiotherapy. Clinical data show a good early hematological tolerance of hypofractionated radiotherapy (both large field and for stereotactic body radiotherapy). There are, however, no data available that assess late hematological toxicity. Evidence on acute hematological toxicity after hypofractionated radiotherapy does not suggest any significant impact of altered fractionation on early treatment tolerance, although further research to assess this problem is needed. The effect of hypofractionation on late hematological tolerance is unknown because the data are still lacking.
Radiotherapy Reduces Microhardness and Mineral and Organic Composition, and Changes the Morphology of Primary Teeth: An in vitro Study
Authors: Marangoni-Lopes Lenita , Rovai-Pavan Gabriela , Steiner-Oliveira Carolina , Nobre-dos-Santos Marinês
Published: October 2018

Objective: We aimed to evaluate whether radiotherapy causes changes in the mineral composition, hardness, and morphology of enamel and dentin of primary teeth. Materials and Methods: Thirty specimens of primary teeth were subjected to radiotherapy. At baseline and after 1,080, 2,160, and 3,060 cGy, the specimens were subjected to microhardness, FT-Raman spectroscopy, and scanning electron microscopy (SEM) analysis. The pH of artificial saliva was determined, as were the calcium and phosphate concentrations. The data were subjected to the Shapiro-Wilk normality test, showed a nonnormal distribution, and were compared by the Kruskal-Wallis test. Results: The results showed that the microhardness of the enamel surface decreased after 2,160 cGy (281.5 ± 58 kgf/mm2) when compared to baseline (323.6 ± 59.5 kgf/mm2) (p = 0.045). For dentin, the surface hardness decreased after 1,080 cGy (34.9 ± 11.4 kgf/mm2) and 2,160 cGy (26 ± 3.5 kgf/mm2) when compared to baseline (56.5 ± 7.7 kgf/mm2) (p < 0.0001). The mineral and organic contents of phosphate (p < 0.0001), carbonate (p < 0.0001), amide (p = 0.0002), and hydrocarbons (p = 0.0031) of enamel decreased after 3,060 cGy (5,178 ± 1,082, 3,868 ± 524, 999 ± 180, and 959 ± 168 kgf/mm2, respectively). For dentin, we noticed a growing increase in phosphate v2, amide, and hydrocarbon content after 1,080 cGy (8,210 ± 2,599, 5,730 ± 1,818, and 6,118 ± 1,807 kgf/mm2, respectively) and 2,160 cGy (1,0071 ± 2,547, 7,746 ± 1,916, and 8,280 ± 2,079 kgf/mm2, respectively) and a reduction after 3,060 cGy (6,782 ± 2,175, 3,558 ± 1,884, and 3,565 ± 1,867 kgf/mm2, respectively) (p < 0.0001). SEM images showed cracks on enamel and degradation of peritubular dentin. Conclusion: We concluded that radiotherapy caused a reduction in surface hardness, changed mineral and organic composition, and promoted morphological changes on the enamel and dentin of primary teeth.
Renal Cell Carcinoma with Venous Thrombus: Should Surgery Be Offered When Metastasis Is Present at Diagnosis?
Authors: Manso Margarida , Pacheco-Figueiredo Luís , Santos-Silva André , Silva João , Silva Carlos , Cruz Francisco
Published: October 2018

Introduction: Renal cell carcinoma (RCC) reveals a tendency towards venous invasion in its advanced stages, making clinical management challenging. Survival may be improved following surgery, but is less clear if it applies to patients with metastatic disease at diagnosis. Materials and Methods: Review of clinical files of patients submitted to surgery for RCC at our institution. Results: Twenty-one patients underwent radical nephrectomy and thrombectomy from 2000 to 2017, with a median follow-up of 25 months. Eighteen (85.7%) men and 3 (14.3%) women, with median age of 63 at the time of diagnosis, were included. The thrombus was in the renal vein in 10 (47.6%) patients and had extension to inferior vena cava (IVC) in 11 (52.4%). The level of involvement in IVC was grade II in 4 (19%) cases, grade III in 4 (19%) cases and grade IV in 3 (14.4%) cases. Surgery was successful in all but 1 patient. Ten patients died during the follow-up (47.6%), resulting in a 5-year overall survival of 34.8%. When considering the metastatic population at diagnosis, the overall survival at 5 years was 45.7%. Conclusion: Radical nephrectomy with removal of the venous thrombus remains the preferential treatment for patients with RCC with venous thrombus, even if they have metastatic disease at diagnosis.
High Glucose Induces VEGF-C Expression via the LPA1/3-Akt-ROS-LEDGF Signaling Axis in Human Prostate Cancer PC-3 Cells
Authors: Huang Yuan-Li , Lin Yueh-Chien , Lin Chu-Cheng , Chen Wei-Min , Chen Benjamin P.C. , Lee Hsinyu
Published: October 2018

Background/Aims: Hyperglycemia has been shown to increase the incidence and metastasis in various types of cancers. However, the correlation between hyperglycemia and lymphatic metastasis in prostate cancer (PCa) remains unclear. Our previous study demonstrated that lysophosphatidic acid (LPA) enhances vascular endothelial growth factor-C (VEGF-C) expression, a lymphangiogenic factor, through activating it receptors LPA1/3 in prostate cancer (PCa) cells. Moreover, hyperglycemia up-regulates autotaxin (ATX) expression, a LPA-generating enzyme. Therefore, we propose that high glucose promotes VEGF-C expression through LPA signaling in PCa cells. Methods: Pharmacological inhibitors and siRNAs were utilized to investigate the molecular mechanism of high glucose-induced VEGF-C expression. Real-time PCR and Western blot were used to determine the mRNA and protein expressions, respectively. Cellular bioenergetics analysis was performed to determine the glycolysis levels. Results: We demonstrated that the expressions of VEGF-C, ATX, and calreticulin were increased upon high glucose treatments in PC-3 cells. Moreover, high glucose-induced VEGF-C expression was mediated through the LPA1/3, PLC, Akt, ROS and LEDGF-dependent pathways. Additionally, high glucose enhanced the aerobic glycolysis via LPA1/3. Conclusion: These results indicated that hyperglycemia leads to LPA synthesis, and subsequent promoting pathological consequence of PCa. These novel findings could potentially provide new strategies for PCa treatments.
Clinical Presentation of Gastrointestinal Stromal Tumors
Authors: Menge Franka , Jakob Jens , Kasper Bernd , Smakic Armand , Gaiser Timo , Hohenberger Peter
Published: October 2018

Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal neoplasms of the gastrointestinal tract. They constitute 1-2% of all gastrointestinal neoplasms but are the most common subtype of soft tissue sarcomas, accounting for 20-25%. In the late 1990s, GISTs were more and more recognized as a particular tumor entity. The tumors are supposed to originate from the interstitial pacemaker cells of Cajal. They are usually well circumscribed and can be located in every part of the tubular gastrointestinal tract. Most often GISTs occur in the stomach, followed by the small bowel and colon/rectum. In contrast to epithelial tumors, GISTs grow transmurally and submucosal. GISTs can be found with highly variable growth features including tumors with intraluminal, intra- or transmural, and pedunculated appearance. Here we describe the most common clinical presentation of GISTs on the basis of our 809 patients managed from 2004 to 2017. The median age of our patients was 59 years and the average size of GIST was 75 mm (range: 4 mm to 35 cm). The clinical presentation is very heterogeneous, depending on tumor site, size, and growth pattern. GISTs of the stomach is the group with the lowest rate of acute or emergency symptoms with 31%, followed by GISTs of the duodenum with 42%, whereas GISTs of the small bowel show acute symptoms in more than 50% of the cases and have an emergency surgery rate of almost 15%. Many patients are diagnosed accidentally, through screening examinations, or with latent, unspecific symptoms.
LRP1 (Low-Density Lipoprotein Receptor–Related Protein 1) Regulates Smooth Muscle Contractility by Modulating Ca
2+
Signaling and Expression of Cytoskeleton-Related Proteins
Authors: Au Dianaly T. , Ying Zhekang , Hernández-Ochoa Erick O. , Fondrie William E. , Hampton Brian , Migliorini Mary , Galisteo Rebeca , Schneider Martin F. , Daugherty Alan , Rateri Debra L. , Strickland Dudley K. , Muratoglu Selen C.
Published: October 2018

Objective—

Mutations affecting contractile-related proteins in the ECM (extracellular matrix), microfibrils, or vascular smooth muscle cells can predispose the aorta to aneurysms. We reported previously that the LRP1 (low-density lipoprotein receptor–related protein 1) maintains vessel wall integrity, and
smLRP1
−/−
mice exhibited aortic dilatation. The current study focused on defining the mechanisms by which LRP1 regulates vessel wall function and integrity.

Approach and Results—

Isometric contraction assays demonstrated that vasoreactivity of LRP1-deficient aortic rings was significantly attenuated when stimulated with vasoconstrictors, including phenylephrine, thromboxane receptor agonist U-46619, increased potassium, and L-type Ca
2+
channel ligand FPL-64176. Quantitative proteomics revealed proteins involved in actin polymerization and contraction were significantly downregulated in aortas of
smLRP1
−/−
mice. However, studies with calyculin A indicated that although aortic muscle from
smLRP1
−/−
mice can contract in response to calyculin A, a role for LRP1 in regulating the contractile machinery is not revealed. Furthermore, intracellular calcium imaging experiments identified defects in calcium release in response to a RyR (ryanodine receptor) agonist in
smLRP1
−/−
aortic rings and cultured vascular smooth muscle cells.

Conclusions—

These results identify a critical role for LRP1 in modulating vascular smooth muscle cell contraction by regulating calcium signaling events that potentially protect against aneurysm development.
Endothelial Cell–Specific Inactivation of TSPAN12 (Tetraspanin 12) Reveals Pathological Consequences of Barrier Defects in an Otherwise Intact Vasculature
Authors: Zhang Chi , Lai Maria B. , Pedler Michelle G. , Johnson Verity , Adams Ralf H. , Petrash J. Mark , Chen Zhe , Junge Harald J.
Published: October 2018

Objective—

Blood-CNS (central nervous system) barrier defects are implicated in retinopathies, neurodegenerative diseases, stroke, and epilepsy, yet, the pathological mechanisms downstream of barrier defects remain incompletely understood. Blood-retina barrier (BRB) formation and retinal angiogenesis require β-catenin signaling induced by the ligand norrin (NDP [Norrie disease protein]), the receptor FZD4 (frizzled 4), coreceptor LRP5 (low-density lipoprotein receptor-like protein 5), and the tetraspanin TSPAN12 (tetraspanin 12). Impaired NDP/FZD4 signaling causes familial exudative vitreoretinopathy, which may lead to blindness. This study seeked to define cell type-specific functions of TSPAN12 in the retina.

Approach and Results—

A loxP-flanked
Tspan12
allele was generated and recombined in endothelial cells using a tamoxifen-inducible Cdh5-CreERT2 driver. Resulting phenotypes were documented using confocal microscopy. RNA-Seq, histopathologic analysis, and electroretinogram were performed on retinas of aged mice. We show that TSPAN12 functions in endothelial cells to promote vascular morphogenesis and BRB formation in developing mice and BRB maintenance in adult mice. Early loss of TSPAN12 in endothelial cells causes lack of intraretinal capillaries and increased VE-cadherin (CDH5 [cadherin5 aka VE-cadherin]) expression, consistent with premature vascular quiescence. Late loss of TSPAN12 strongly impairs BRB maintenance without affecting vascular morphogenesis, pericyte coverage, or perfusion. Long-term BRB defects are associated with immunoglobulin extravasation, complement deposition, cystoid edema, and impaired b-wave in electroretinograms. RNA-sequencing reveals transcriptional responses to the perturbation of the BRB, including genes involved in vascular basement membrane alterations in diabetic retinopathy.

Conclusions—

This study establishes mice with late endothelial cell–specific loss of
Tspan12
as a model to study pathological consequences of BRB impairment in an otherwise intact vasculature.
Impaired HDL (High-Density Lipoprotein)-Mediated Macrophage Cholesterol Efflux in Patients With Abdominal Aortic Aneurysm—Brief Report
Authors: Martínez-López Diego , Cedó Lídia , Metso Jari , Burillo Elena , García-León Annabel , Canyelles Marina , Lindholt Jes S. , Torres-Fonseca Monica , Blanco-Colio Luis Miguel , Vázquez Jesús , Blanco-Vaca Francisco , Jauhiainen Matti , Martín-Ventura Jose Luis , Escolà-Gil Joan Carles
Published: October 2018

Objective—

The ability of HDL (high-density lipoprotein) to promote macrophage cholesterol efflux is considered the main HDL cardioprotective function. Abdominal aortic aneurysm (AAA) is usually characterized by cholesterol accumulation and macrophage infiltration in the aortic wall. Here, we aim to evaluate the composition of circulating HDL particles and their potential for promoting macrophage cholesterol efflux in AAA subjects.

Approach and Results—

First, we randomly selected AAA and control subjects from Spain. The AAA patients in the Spanish cohort showed lower plasma apoA-I levels concomitantly associated with low levels of plasma HDL cholesterol and the amount of preβ-HDL particles. We determined macrophage cholesterol efflux to apoB-depleted plasma, which contains mature HDL, preβ-HDL particles and HDL regulatory proteins. ApoB-depleted plasma from AAA patients displayed an impaired ability to promote macrophage cholesterol efflux. Next, we replicated the experiments with AAA and control subjects derived from Danish cohort. Danish AAA patients also showed lower apoA-I levels and a defective HDL-mediated macrophage cholesterol efflux.

Conclusions—

AAA patients show impaired HDL-facilitated cholesterol removal from macrophages, which could be mechanistically linked to AAA.
Association Between Incomplete Circle of Willis and Carotid Vulnerable Atherosclerotic Plaques
Authors: Zhou Changwu , Yuan Chun , Li Rui , Wang Wei , Li Cheng , Zhao Xihai ,   on behalf of the CARE-II Study Collaborators
Published: October 2018

Objective—

Carotid high-risk plaque, characterized by intraplaque hemorrhage, fibrous cap rupture, and large lipid-rich necrotic core, is associated with cerebrovascular events. This study sought to investigate the relationship between high-risk carotid plaque and an incomplete circle of Willis (COW).

Approach and Results—

Patients were recruited from a multicenter study, Chinese Atherosclerosis Risk Evaluation (CARE-II) and underwent 3-dimensional time-of-flight magnetic resonance angiography for intracranial arteries and 2-dimensional multicontrast magnetic resonance vessel wall imaging for carotid arteries on a 3.0T magnetic resonance scanner. The integrity of the COW in anterior and posterior portions was evaluated. Characteristics of carotid plaques were assessed. Correlation between incomplete COW and carotid plaque features was determined. Of 482 eligible patients, patients with carotid intraplaque hemorrhage showed significantly higher prevalence of an incomplete anterior COW (52.7% versus 38.5%;
P
=0.022) compared with those without. An incomplete anterior COW was associated with intraplaque hemorrhage before (odds ratio, 1.781; 95% CI, 1.083–2.931;
P
=0.023) and after adjusted for clinical risk factors (odds ratio, 1.945; 95% CI, 1.139–3.321;
P
=0.015). The unilateral carotid artery stenosis showed no correlation with incomplete anterior COW and posterior COW (all
P
>0.025). No significant associations were found between other plaque features and any type of incomplete COW (all
P
>0.025).

Conclusions—

An incomplete COW is independently associated with intraplaque hemorrhage of carotid atherosclerotic plaques.

Clinical Trial Registration—

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT02017756.
To Turn Soybeans into Gold: a Case Study of Mortuary Documents from Ancient China
Authors: Wen Jiang
Published: October 2018

The Eastern Han period tomb-quelling text of Zhang Shujing 張叔敬, which dates to 173 CE, confirms that living people believed the dead could use soybeans and melon seeds (huangdou guazi 黃豆瓜子) to pay taxes in the underworld. The knowledge of this only came to light with the discovery of the tablet Taiyuan Has a Dead Man (*Taiyuan you sizhe 泰原有死者), which reveals a previously unknown Qin-Han belief that the dead regarded soybeans as gold. I suggest a direct association between the above two beliefs: soybeans and melon seeds were used as substitutes for small natural gold nuggets to pay taxes in the underworld because of their resemblance in shape and color. Furthermore, a huge quantity of painted clay balls shaped like large soybeans (dashu 大菽) are recorded in the Mawangdui 馬王堆 tomb inventories (qiance 遣策), which indirectly supports this interpretation.
Development of an Instrument to Assess Work Productivity in Individuals With Voice Disorders: The Work Hoarse
Authors: Zhu Qiubei , Hu Amanda , Giliberto John Paul , Carlson Samantha , Jensen Samantha , Tiu Ryan , Meyer Tanya K.
Published: October 2018

Objectives:

Vocal function is critical to employability in the modern era. Although research clearly demonstrates that a disordered voice affects quality of life, few studies have attempted to quantitate the effects of a disordered voice on work productivity. The Voice-Related Statements battery, which originally had 20 items, was previously developed to qualitatively describe how an individual’s dysphonia affects his or her job performance. The aim of this study was to refine and reduce the item number and provide preliminary validation of this shortened instrument.

Methods:

The Voice-Related Statements instrument was administered to employed patients with dysphonia in conjunction with 2 additional instruments: the Voice Handicap Index (VHI) and the Work Productivity and Activity Impairment questionnaire (WPAI). Response distributions and intercorrelations were examined for item reduction. Exploratory factor analysis was conducted on retained items. Correlations were performed with other voice-related instruments. Reliability was tested using a coefficient of stability.

Results:

One hundred seventy-four employed patients with dysphonia were enrolled in this study. Six items were removed because of redundancy, factor analysis, and cognitive interview results. Exploratory factor analysis revealed a 1-factor structure explaining 66.28% of the total variance. The final 8-item instrument demonstrated good internal consistency (Cronbach α = 0.93), with a moderately robust correlation with the VHI ( r = 0.68, P < .001) and WPAI work impairment measures ( r = 0.63, P < .001). The VHI showed a much weaker correlation with WPAI work impairment ( r = 0.48, P < .001). Test-retest reliability was good (0.83, P < .01).

Conclusions:

An 8-item instrument to qualitatively measure the impact of a disordered voice at work has been developed and is called the Work Hoarse. This instrument is a better measure of voice-related work productivity impairment than the VHI and will augment quantitative work productivity instruments that are currently available.
The Relation between Train Access Mode Attributes and Travelers’ Transport Mode-Choice Decisions in the Context of Medium- and Long-Distance Trips in the Netherlands
Authors: van der Waerden Peter , van der Waerden Jaap
Published: October 2018

This paper presents the findings of a study that investigated travelers’ transport mode-choice behavior in the context of medium- and long-distance trips, with special attention given to attributes of train access modes. The goal of the paper is to provide greater insight into the contribution of both access and main travel-mode attributes to the travelers’ decision to use the car or the train for medium- and long-distance trips. Based on data collected through a stated choice experiment, a mixed logit model is estimated to identify the contributions of all included attributes. In total, 32 attributes were included in the experiment describing the main transport modes, train and car, and the access modes: bicycle, bus, and drop-off/car. Based on a fractional factorial design, the attributes and corresponding levels were combined into 81 different mode-choice situations. The stated choice experiment was included in an online questionnaire that was distributed among members of a marketing panel. Panel members were invited to choose the preferred travel-mode for a medium- and long-distance trip given a detailed description of both main and access modes. Each member evaluated nine choice situations. In total, 415 panel members completed the questionnaire. Combined, panel members evaluated 3,735 choice situations. The mixed logit model analysis shows that time and cost-related attributes significantly contribute to the attractiveness of transport modes. However, these effects differ considerably between the investigated modes. Conversely, safety-related attributes, chance of delay, and transfer time from access mode to train platform play a minor role.
Effects of circular holes on the web warping of perforated blanks in flexible roll forming
Authors: Kang Pil Gyu , Woo Young Yun , Moon Young Hoon
Published: October 2018

To meet the demands of highly functional parts, high-precision manufacturing technology that can provide sound semifinal perforated components having variable cross sections is frequently required. When a relatively short blank is formed into a variable section by a flexible roll forming process, web warping such as longitudinal bows and crossbows can be generated in the formed products. In this study, the characteristic features of web warping occurring in the flexible roll forming of perforated blanks were investigated both numerically and experimentally. In order to investigate the cause of web warping, the stress and strain variations during flexible roll forming are examined in terms of the shapes of blank and hole orientations of perforated blanks. The results show that longitudinal bows and crossbows are primarily caused by the nonuniformity of longitudinal and transverse strains between the flange and the web. In addition, the degree of web warping is sensitive to the shapes of the blanks and the hole orientations. From the process analysis, a guideline for the perforation of holes in convex, concave and trapezoid blanks is proposed to reduce web warping.
Density estimation based on the Hounsfield unit value of cone beam computed tomography imaging of the jawbone system
Authors: Genisa Maya , Shuib Solehuddin , Rajion Zainul Ahmad , Arief Erry Mochamad , Hermana Maman
Published: October 2018

The aim of this study is to investigate the estimation of density from the Hounsfield unit of cone beam computed tomography data in dental imaging, especially for dental implant application. A jaw phantom with various known densities of anatomical parts (e.g. soft tissue, cortical bone, trabecular bone, tooth enamel, tooth dentin, sinus cavity, spinal cord and spinal disc) has been used to test the accuracy of the Hounsfield unit of cone beam computed tomography in estimating the mechanical density (true density). The Hounsfield unit of cone beam computed tomography data was evaluated via the MIMICS software using both two-dimensional and three-dimensional methods, and the results showed correlation with the true density of the object. In addition, the results revealed that the Hounsfield unit of cone beam computed tomography and bone density had a logarithmic relation, rather than a linear one. To this end, the correlation coefficient of logarithmic correlation (R2 = 0.95) is higher than the linear one (R2 = 0.77).
Decomposing the determinants of fathers’ parental leave use: Evidence from migration between Finland and Sweden
Authors: Mussino Eleonora , Tervola Jussi , Duvander Ann-Zofie
Published: October 2018

The use of parental leave by fathers varies notably between countries. However, the underlying reasons for cross-country differences have not been explicitly studied. We use migration between Finland and Sweden as an instrument to decompose the roles of policy design and social norms in the differences in take-up rates between these two countries. First, we inferred the role of policy by looking at fathers from the same country of origin in various policy contexts. Second, we deduced the role of norms by examining fathers who migrated at different ages and fathers with spouses of different origins. We find that the large cross-country differences in fathers’ use of parental leave between Finland and Sweden mainly stem from differences in policy design. Norms seem to play a smaller but still significant role.
Combined piezoelectric and flexoelectric effects in resonant dynamics of nanocantilevers
Authors: Moura Adriane G , Erturk Alper
Published: October 2018

We establish and analyze an analytical framework by accounting for both the piezoelectric and flexoelectric effects in bimorph cantilevers. The focus is placed on the development of governing electroelastodynamic piezoelectric–flexoelectric equations for the problems of resonant energy harvesting, sensing, and actuation. The coupled governing equations are analyzed to obtain closed-form frequency response expressions via modal analysis. The combined piezoelectric–flexoelectric coupling coefficient expression is identified and its size dependence is explored. Specifically, a typical atomistic value of the flexoelectric constant for barium titanate is employed in the model simulations along with its piezoelectric constant from the existing literature. It is shown that the effective electromechanical coupling of a piezoelectric material, such as barium titanate, is significantly enhanced for thickness levels below 100 nm. The electromechanical coupling coefficient of a barium titanate bimorph cantilever increases from the bulk piezoelectric value of 0.065 to the combined piezoelectric–flexoelectric value exceeding 0.3 toward nanometer thickness level. Electromechanical frequency response functions for resonant power generation and dynamic actuation also capture the size-dependent enhancement of the electromechanical coupling. The analytical framework given here can be used for parameter identification and design of nanoscale cantilevers that can be used as energy harvesters, sensors, and actuators.
Facilitating Course Connections and Transitions to Project Closure in Service Learning
Authors: Choi Eunhee , Raymond Jenna , Hentschel Margit
Published: October 2018

Background:The ability to forge connections between academic study and real-world experience is essential in service learning (SL). Furthermore, the transition out of SL projects can be emotionally charged for both students and service recipients; yet, little research has been conducted on this topic. Purpose: This study aimed (a) to compare students’ ability to forge connections between course content and service experience and (b) to compare the transition out of their SL project between the 2016 and 2017 cohorts. Methodology/Approach: Mixed methods were used for the comparison. T tests were conducted to compare differences in the exam scores between the two cohorts. Summative content analysis was used to compare students’ weekly reflection journals for the two cohorts. Findings/Conclusions: Students were better able to make such connections when they were explicitly guided with prompting questions based on each week’s lecture topics. Students also transitioned out of their projects more smoothly when provided with a lecture, abundant reflection opportunities, and more instructor coaching. Exam scores, however, showed no statistical differences between the cohorts. Implications: Intentional efforts must be made to ensure that students relate course content to their service experience. Providing guidance on transitioning to project closure would also benefit students.