bluuebunny/crossref_metadata_2025_split huggingface dataset:
Epigenetic Regulation of Dlg1, via Kaiso, Alters Mitotic Spindle Polarity and Promotes Intestinal Tumorigenesis
Authors: Young Madeleine A. , May Stephanie , Damo Angelos , Yoon Young So , Hur Man-Wook , Swat Wojiech , Parry Lee 
Published: December 2018

Abstract

Both alterations to the epigenome and loss of polarity have been linked to cancer initiation, progression, and metastasis. It has previously been demonstrated that loss of the epigenetic reader protein Kaiso suppresses intestinal tumorigenesis in the Apc+/min mouse model, in which altered polarity plays a key role. Thus, we investigated the link between Kaiso deficiency, polarity, and suppression of intestinal tumorigenesis. We used Kaiso-deficient mice to conditionally delete Apc within the intestinal epithelia and demonstrated upregulation of the spindle polarity genes Dlg1 and Dlgap1. To understand the role of Dlg1, we generated Villin-creApc+/minDlg1flx/flx Kaiso−/y mice to analyze gene expression, survival, tumor burden, and spindle orientation. In vivo analysis of the Dlg1-deficient intestine revealed improper orientation of mitotic spindles and a decreased rate of cellular migration. Loss of Dlg1 decreased survival in Apc+/min mice, validating its role as a tumor suppressor in the intestine. Significantly, the increased survival of Apc+/minKaisoy/− mice was shown to be dependent on Dlg1 expression. Taken together, these data indicate that maintenance of spindle polarity in the intestinal crypt requires appropriate regulation of Dlg1 expression. As Dlg1 loss leads to incorrect spindle orientation and a delay in cells transiting the intestinal crypt. We propose that the delayed exit from the crypt increase the window in which spontaneous mutations can become fixed, producing a “tumor-permissive” environment, without an increase in mutation rate.

Implications:
Loss of mitotic spindle polarity delays the exit of cells from the intestinal crypt and promotes a tumorigenic environment.
CCL2 Is a Vascular Permeability Factor Inducing CCR2-Dependent Endothelial Retraction during Lung Metastasis
Authors: Roblek Marko , Protsyuk Darya , Becker Paul F. , Stefanescu Cristina , Gorzelanny Christian , Glaus Garzon Jesus F. , Knopfova Lucia , Heikenwalder Mathias , Luckow Bruno , Schneider Stefan W. , Borsig Lubor 
Published: December 2018

Abstract

Increased levels of the chemokine CCL2 in cancer patients are associated with poor prognosis. Experimental evidence suggests that CCL2 correlates with inflammatory monocyte recruitment and induction of vascular activation, but the functionality remains open. Here, we show that endothelial Ccr2 facilitates pulmonary metastasis using an endothelial-specific Ccr2-deficient mouse model (Ccr2ecKO). Similar levels of circulating monocytes and equal leukocyte recruitment to metastatic lesions of Ccr2ecKO and Ccr2fl/fl littermates were observed. The absence of endothelial Ccr2 strongly reduced pulmonary metastasis, while the primary tumor growth was unaffected. Despite a comparable cytokine milieu in Ccr2ecKO and Ccr2fl/fl littermates the absence of vascular permeability induction was observed only in Ccr2ecKO mice. CCL2 stimulation of pulmonary endothelial cells resulted in increased phosphorylation of MLC2, endothelial cell retraction, and vascular leakiness that was blocked by an addition of a CCR2 inhibitor. These data demonstrate that endothelial CCR2 expression is required for tumor cell extravasation and pulmonary metastasis.

Implications:
The findings provide mechanistic insight into how CCL2–CCR2 signaling in endothelial cells promotes their activation through myosin light chain phosphorylation, resulting in endothelial retraction and enhanced tumor cell migration and metastasis.
Validation of Resting Diastolic Pressure Ratio Calculated by a Novel Algorithm and Its Correlation With Distal Coronary Artery Pressure to Aortic Pressure, Instantaneous Wave–Free Ratio, and Fractional Flow Reserve
Authors: Ligthart Jurgen , Masdjedi Kaneshka , Witberg Karen , Mastik Frits , van Zandvoort Laurens , Lemmert Miguel E. , Wilschut Jeroen , Diletti Roberto , de Jaegere Peter , Zijlstra Felix , Kardys Isabella , Van Mieghem Nicolas M , Daemen Joost 
Published: December 2018

Background:
Instantaneous wave–free ratio (iFR) offers a reliable non–hyperemic assessment of coronary physiology but requires dedicated proprietary software with a fully automated algorithm. We hypothesized that dPR (diastolic pressure ratio), calculated with novel universal software, has a strong correlation with iFR, similar diagnostic accuracy relative to resting distal coronary artery pressure/aortic pressure and fractional flow reserve (FFR).

Methods and Results:

The dPR study is an observational, retrospective, single-center cohort study including patients who underwent iFR or FFR. Dedicated software was used to calculate the dPR from Digital Imaging and Communications in Medicine (DICOM) pressure waveforms. The flat period on the pressure difference between sample (dP) to the time difference between the same sample points (dt) signal was used to detect automatically the period, where the resistance is low and constant, and to calculate the dPR, which is an average over 5 consecutive heartbeats. The software was validated by correlating iFR results with dPR. Software validation was done by comparing 78 iFR measurements in 44 patients who underwent iFR. Mean iFR and dPR were 0.91±0.10 and 0.92±0.10, respectively, with a significant linear correlation (
R
=0.997;
P
<0.001). Diagnostic accuracy was tested in 100 patients who underwent FFR. Mean FFR, resting distal coronary artery pressure/aortic pressure, and dPR were 0.85±0.09, 0.94±0.05, and 0.93±0.07, respectively. There was a significant linear correlation between dPR and FFR (
R
=0.77;
P
<0.001). Both distal coronary artery pressure/aortic pressure and dPR had good diagnostic accuracy in the identification of lesions with an FFR ≤0.80 (area under the curve, 0.84; 95% CI, 0.76–0.92 and 0.86; 95% CI, 0.78–0.93, respectively).

Conclusions:
dPR, calculated by a novel validated software tool, showed a strong linear correlation with iFR. dPR correlated well with FFR with a good diagnostic accuracy to identify positive FFR.
Revisiting the Optimal Fractional Flow Reserve and Instantaneous Wave-Free Ratio Thresholds for Predicting the Physiological Significance of Coronary Artery Disease
Authors: Modi Bhavik N. , Rahman Haseeb , Kaier Thomas , Ryan Matthew , Williams Rupert , Briceno Natalia , Ellis Howard , Pavlidis Antonis , Redwood Simon , Clapp Brian , Perera Divaka 
Published: December 2018

Background:
There has been a gradual upward creep of revascularization thresholds for both fractional flow reserve (FFR) and instantaneous wave-free ratio (iFR), before the clinical outcome trials for both indices. The increase in revascularization that has potentially resulted is at odds with increasing evidence questioning the benefits of revascularizing stable coronary disease. Using an independent invasive reference standard, this study primarily aimed to define optimal thresholds for FFR and iFR and also aimed to compare the performance of iFR, FFR, and resting distal coronary pressure (Pd)/central aortic pressure (Pa).

Methods and Results:

Pd and Pa were measured in 75 patients undergoing coronary angiography±percutaneous coronary intervention with resting Pd/Pa, iFR, and FFR calculated. Doppler average peak flow velocity was simultaneously measured and hyperemic stenosis resistance calculated as hyperemic stenosis resistance=Pa−Pd/average peak flow velocity (using hyperemic stenosis resistance >0.80 mm Hg/cm per second as invasive reference standard). An FFR threshold of 0.75 had an optimum diagnostic accuracy (84%), whereas for iFR this was 0.86 (76%). At these thresholds, the discordance in classification between indices was 11%. The accuracy of contemporary thresholds (FFR, 0.80; iFR, 0.89) was significantly lower (78.7% and 65.3%, respectively) with a 25% rate of discordance. The optimal threshold for Pd/Pa was 0.88 (77.3% accuracy). When comparing indices at optimal thresholds, FFR showed the best diagnostic performance (area under the curve, 0.91 FFR versus 0.79 iFR and 0.77 Pd/Pa,
P
=0.002).

Conclusions:
Contemporary thresholds provide suboptimal diagnostic accuracy compared with an FFR threshold of 0.75 and iFR threshold of 0.86 (cutoffs in derivation studies). Whether more rigorous thresholds would result in selecting populations gaining greater symptom and prognostic benefit needs assessing in future trials of physiology-guided revascularization.
At the Margins of Architectural and Landscape History: The Rajputs of South Asia
Authors: Fairchild Ruggles D. 
Published: December 2018

The Rajput princes of South Asia in the sixteenth to nineteenth centuries built beautiful palaces with gardens and commissioned manuscript paintings that rivaled those of their Mughal contemporaries. Although the Hindu Rajputs and Muslim Mughals were variously allies and foes, neither political relations nor religious faith prevented artistic exchanges from occurring between them. Just as the Mughals embraced and internalized Indic forms such as the chhatri, the Rajputs likewise appropriated forms such as the four-part garden known as the chahar bagh, not as a direct transfer but a reworking and renegotiation of form and expression. While the Rajput chahar baghs are the only ones to have attracted the attention of historians, most likely because they fit neatly into a recognized architectural type, Rajput patrons also built other kinds of gardens with rectilinear and curving parterres, deep pools with “floating” pavilions, lotus gardens, and orchards resembling sacred groves. Some of these appear in Mughal sites too, typically inserted into a chahar bagh. The essay looks at how typological forms were shared and adapted by the Mughals and Rajputs, and asks what such forms may have meant to their respective patrons. It concludes by proposing that the definition of art historical fields—divided along religious lines between Islam and Hinduism—often impedes such inquiries.
再論漢語方言的形態類型
Authors: Arcodia Giorgio Francesco 
Published: December 2018

提要
學者們通常認為漢語是典型的孤立語，詞綴較少，由來知根知底 (Sagart 2004)。本文首先對孤立語的概念進行“解構”。接著，基於山西、陝西、河南、河北以及山東方言的語料，說明漢語方言中似乎存在著地域上成片的具有能產性的形態現象，而這種現象似乎不該出現在孤立語中。本文認為，產生這類形態現象的動因包括語法化標記語音侵蝕的普遍傾向以及方言之間的互相影響。
From the Viewpoint of Historical Grammar: 從歷史語法的觀點論「乞」在閩語中的演變
Authors: Wu Rui-wen 
Published: December 2018

提要
本文從歷史語法的角度，探討「乞」在現代閩語方言中的演變，說明「乞」在閩語中具有的功能，包括實詞語義及功能詞用法，並嘗試從方言比較的角度建構「乞」在閩語語法史上的語法演變。根據漢語歷史文獻，「乞」有乞求義跟給予義兩個方向不同的動詞用法，並透過四聲別義的手段來區別。從現代閩語方言看來，閩東方言及局部閩南方言使用「乞」作為被動標記。本文結合早期閩語書面材料及實際調查所得的語料，探究「乞」在閩語中的音韻、詞彙及語法演變。本文的結論如下：1. 音韻方面，「乞」在共同閩語中的語音形式為*kʰɨt7，只有入聲而沒有去聲。2. 詞彙方面，閩語的「乞」同時存在乞求義與給予義兩種實詞用法。3. 就語法演變而言，閩語被動標記「乞」的虛化途徑是：給予義→容讓義→被動標記。
Frenotomy in Infants with Tongue-Tie and Breastfeeding Problems
Authors: Srinivasan Anjana , Al Khoury Alex , Puzhko Svetlana , Dobrich Carole , Stern Meira , Mitnick Howard , Goldfarb Lenore 
Published: December 2018

Background: Infant tongue-tie can cause breastfeeding problems, which may be improved by frenotomy. However, controversy exists among the medical community. Research aim: To examine the influence of frenotomy on infants with posterior ankyloglossia, by quantifying the changes in breastfeeding and maternal nipple pain using standardized tools. Methods: Newborns ( N = 30) below 12 weeks of age were recruited from the Herzl–Goldfarb Breastfeeding Clinic between April 2014 and April 2015. Diagnosis of posterior ankyloglossia was made clinically. Frenotomy was performed. Mothers received breastfeeding counseling before and after the procedure. Pain and breastfeeding were assessed before the procedure, immediately after the procedure, and after 2 days, 7 days and 14 days. Breastfeeding was assessed using the LATCH Tool and by subjective questioning. Maternal nipple pain was assessed using the Numeric Rating System. Results: No complications were reported with frenotomy. There was a significant improvement in LATCH score immediately post-frenotomy, with an increase in median scores from 7.5 to 8.5 ( p < .0001, Wilcoxon signed rank test). There was a significant decrease in median pain score immediately post-frenotomy, from 3.0 on the left nipple and 3.25 on the right nipple, to 0 bilaterally ( p < .0001, Wilcoxon signed rank test). Subjective improvement in breastfeeding was reported by 90% of mothers immediately after frenotomy and 83% of mothers at Day 14. Conclusion: Frenotomy for posterior ankyloglossia may improve breastfeeding and nipple pain.
Cross-Cultural Adaptation and Validation of the Finnish Version of the Michigan Hand Outcomes Questionnaire
Authors: Hulkkonen S. , Repo J. P. , Häkkinen A. , Karppinen J. , Ryhänen J. 
Published: December 2018

Background and Aims: Michigan Hand Outcomes Questionnaire is a widely used patient-reported outcome measure in hand surgery. The aim of this study was to translate and validate the Michigan Hand Outcomes Questionnaire into Finnish for Finnish patients with hand problems following international standards and guidelines. Material and Methods: The original English Michigan Hand Outcomes Questionnaire was translated into Finnish. Altogether, 115 patients completed the Finnish Michigan Hand Outcomes Questionnaire, and reference outcomes: Disabilities of the Arm and Shoulder, EQ-5D 3L and pain intensity on a visual analog scale. Grip and key pinch forces were measured. After 1–2 weeks, 63 patients completed the Finnish Michigan Hand Outcomes Questionnaire the second time. The Michigan Hand Outcomes Questionnaire was analyzed for internal consistency, repeatability, correlations with the reference outcomes, and factor analysis. Results: Cronbach’s alpha ranged from 0.90 to 0.97 in all the Michigan Hand Outcomes Questionnaire subscales, showing high internal consistency. The intraclass correlation coefficient showed good to excellent test–retest reliability ranging from 0.66 to 0.91 in all the Michigan Hand Outcomes Questionnaire subscales. In factor analysis, the structure with six subscales was not confirmed. All the subscales correlated with Disabilities of the Arm and Shoulder score, and five subscales correlated with EQ-5D index. Conclusion: The Finnish version of the Michigan Hand Outcomes Questionnaire showed similar properties compared to the original English version and thus can be used as patient-reported outcome measure for Finnish patients with hand problems.
Affimer proteins as a tool to modulate fibrinolysis, stabilize the blood clot, and reduce bleeding complications
Authors: Kearney Katherine J. , Pechlivani Nikoletta , King Rhodri , Tiede Christian , Phoenix Fladia , Cheah Ramsah , Macrae Fraser L. , Simmons Katie J. , Manfield Iain W. , Smith Kerrie A. , Spurgeon Benjamin E. J. , Naseem Khalid M. , Ariens Robert A. S. , McPherson Michael J. , Tomlinson Darren C. , Ajjan Ramzi A. 
Published: December 2018

AbstractBleeding complications secondary to surgery, trauma, or coagulation disorders are important causes of morbidity and mortality. Although fibrin sealants are considered to minimize blood loss, this is not widely adopted because of its high cost and/or risk for infection. We present a novel methodology employing nonantibody fibrinogen-binding proteins, termed Affimers, to stabilize fibrin networks with the potential to control excessive bleeding. Two fibrinogen-specific Affimer proteins, F5 and G2, were identified and characterized for their effects on clot structure/fibrinolysis, using turbidimetric and permeation analyses and confocal and electron microscopy. Binding studies and molecular modeling identified interaction sites, whereas plasmin generation assays determined effects on plasminogen activation. In human plasma, F5 and G2 prolonged clot lysis time from 9.8 ± 1.1 minutes in the absence of Affimers to 172.6 ± 7.4 and more than 180 minutes (P &lt; .0001), respectively, and from 7.6 ± 0.2 to 28.7 ± 5.8 (P &lt; .05) and 149.3 ± 9.7 (P &lt; .0001) minutes in clots made from purified fibrinogen. Prolongation in fibrinolysis was consistent across plasma samples from healthy control patients and individuals at high bleeding risk. F5 and G2 had a differential effect on clot structure and G2 profoundly altered fibrin fiber arrangement, whereas F5 maintained physiological clot structure. Affimer F5 reduced fibrin-dependent plasmin generation and was predicted to bind fibrinogen D fragment close to tissue plasminogen activator (tPA; residues γ312-324) and plasminogen (α148-160) binding sites, thus interfering with tPA–plasminogen interaction and representing 1 potential mechanism for modulation of fibrinolysis. Our Affimer proteins provide a novel methodology for stabilizing fibrin networks with potential future clinical implications to reduce bleeding risk.
RETRACTED ARTICLE: Propofol suppresses growth, migration and invasion of A549 cells by down-regulation of miR-372
Authors: Sun Hai , Gao Dengyu 
Published: December 2018

Abstract
Background
Propofol, a commonly used intravenous anesthetic during cancer resection surgery, has been found to exhibit tumor inhibitory effects in vitro and in vivo. The role of propofol in lung cancer has been previously reported, whereas its action mechanism remains unclear. This study further investigated the effects of propofol on lung cancer A549 cell growth, migration and invasion, as well as the underlying mechanisms.

Methods
Cell viability, proliferation, migration, invasion and apoptosis were assessed by CCK-8 assay, BrdU assay, two chamber transwell assay and flow cytometry, respectively. The regulatory effect of propofol on microRNA-372 (miR-372) expression in A549 cells was analyzed by qRT-PCR. Cell transfection was used to change the expression of miR-372. The protein expression of key factors involving in cell proliferation, apoptosis, migration and invasion, as well as Wnt/β-catenin and mTOR pathways were analyzed by western blotting.

Results
Propofol inhibited lung cancer A549 cell viability, proliferation, migration, and invasion, but promoted cell apoptosis. Moreover, miR-372 was down-regulated in propofol-treated A549 cells. Overexpression of miR-372 abrogated the effects of propofol on proliferation, migration, invasion and apoptosis of A549 cells. Knockdown of miR-372 had opposite effects. Furthermore, propofol suppressed Wnt/β-catenin and mTOR signaling pathways by down-regulating miR-372.

Conclusion
Propofol inhibits growth, migration and invasion of lung cancer A549 cells at least in part by down-regulating miR-372 and then inactivating Wnt/β-catenin and mTOR pathways.
Evidence for a southward autumn migration of nocturnal noctuid moths in central Europe
Authors: Dreyer David , el Jundi Basil , Kishkinev Dmitry , Suchentrunk Carina , Campostrini Lena , Frost Barrie J. , Zechmeister Thomas , Warrant Eric J. 
Published: December 2018

ABSTRACT
Insect migrations are spectacular natural events and resemble a remarkable relocation of biomass between two locations in space. Unlike the well-known migrations of daytime flying butterflies, such as the painted lady (Vanessa cardui) or the monarch butterfly (Danaus plexippus), much less widely known are the migrations of nocturnal moths. These migrations – typically involving billions of moths from different taxa – have recently attracted considerable scientific attention. Nocturnal moth migrations have traditionally been investigated by light trapping and by observations in the wild, but in recent times a considerable improvement in our understanding of this phenomenon has come from studying insect orientation behaviour, using vertical-looking radar. In order to establish a new model organism to study compass mechanisms in migratory moths, we tethered each of two species of central European Noctuid moths in a flight simulator to study their flight bearings: the red underwing (Catocala nupta) and the large yellow underwing (Noctua pronuba). Both species had significantly oriented flight bearings under an unobscured view of the clear night sky and in the Earth's natural magnetic field. Red underwings oriented south-southeast, while large yellow underwings oriented southwest, both suggesting a southerly autumn migration towards the Mediterranean. Interestingly, large yellow underwings became disoriented on humid (foggy) nights while red underwings remained oriented. We found no evidence in either species for a time-independent sky compass mechanism as previously suggested for the large yellow underwing.
Revised lectotypification of Lycopus europaeus (Lamiaceae)
Authors: Sennikov Alexander N. , Melnikov Denis G. 
Published: December 2018

AbstractThe current lectotype of Lycopus europaeus, Herb. Linnaeus No. 36.1 (LINN), consists of two plant fragments, which represent different species: L. europaeus (as currently applied) and L. exaltatus. The plant on the left, which represents L. europaeus, is designated as a new lectotype because it is the element that is in agreement with the validating diagnosis and the current usage of the name.
Stochastic Network Design for Planning Scheduled Transportation Services: The Value of Deterministic Solutions
Authors: Wang Xin , Crainic Teodor Gabriel , Wallace Stein W. 
Published: December 2018

We study the value of deterministic solutions, in particular their quality and upgradability, in addressing stochastic network design problems, by analyzing their time-dependent formulations known as scheduled service network design problems in freight transportation planning. We study several problem variants and models and investigate, for each case, the immediate quality of the deterministic solutions stemming from the 50th and the 75th percentile of the demand distributions. We then show that for all models, but in different ways, we are able to make effective use of parts of the deterministic solution, confirming the value of the deterministic solution in the stochastic environment, even when the deterministic solution itself performs badly. We also investigate what makes the optimal stochastic solution better in the stochastic environment than other feasible solutions, particularly those obtained by addressing deterministic versions of the problem. We do this by quantitatively analyzing the structures of different solutions. A measurement scheme is proposed to evaluate the level of potentially beneficial structural properties (multipath usage and path sharing) in different solutions. We show that these structural properties are important and correlated with the performance of a solution in the stochastic environment. Data and the online appendix are available at https://doi.org/10.1287/ijoc.2018.0819 .