bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of age and autism spectrum disorder on oxytocin receptor density in the human basal forebrain and midbrain
Authors: Freeman Sara M. , Palumbo Michelle C. , Lawrence Rebecca H. , Smith Aaron L. , Goodman Mark M. , Bales Karen L.
Published: November 2018

The prosocial hormone oxytocin (OXT) has become a new target for research on the etiology and treatment of autism spectrum disorder (ASD), a condition characterized by deficits in social function. However, it remains unknown whether there are alterations in OXT receptor (OXTR) levels in the ASD brain. This study quantified the density of OXTR and of the structurally related vasopressin 1a receptor (AVPR1a) in postmortem brain tissue from individuals with ASD and typically developing individuals. We analyzed two regions known to contain OXTR across all primates studied to date: the nucleus basalis of Meynert (NBM), which mediates visual attention, and the superior colliculus, which controls gaze direction. In the NBM specimens, we also analyzed the neighboring ventral pallidum (VP) and the external segment of the globus pallidus. In the superior colliculus specimens, we also analyzed the adjacent periaqueductal gray. We detected dense OXTR binding in the human NBM and VP and moderate to low OXTR binding in the human globus pallidus, superior colliculus, and periaqueductal gray. AVPR1a binding was negligible across all five regions in all specimens. Compared to controls, ASD specimens exhibited significantly higher OXTR binding in the NBM and significantly lower OXTR binding in the VP, an area in the mesolimbic reward pathway. There was no effect of ASD on OXTR binding in the globus pallidus, superior colliculus, or periaqueductal gray. We also found a significant negative correlation between age and OXTR binding in the VP across all specimens. Further analysis revealed a peak in OXTR binding in the VP in early childhood of typically developing individuals, which was absent in ASD. This pattern suggests a possible early life critical period, which is lacking in ASD, where this important reward area becomes maximally sensitive to OXT binding. These results provide unique neurobiological insight into human social development and the social symptoms of ASD.
Prebiotic plausibility and networks of paradox-resolving independent models
Authors: Benner Steven A.
Published: November 2018

The plausibility of any model in science comes from the extent of its interconnections to other models that are grounded in different premises and reasoning. Focusing research on paradoxes in those models, logic whereby they appear to generate unacceptable conclusions from seemingly indisputable premises, helps find those interconnections.
A semi-supervised approach for predicting cell-type specific functional consequences of non-coding variation using MPRAs
Authors: He Zihuai , Liu Linxi , Wang Kai , Ionita-Laza Iuliana
Published: November 2018

Predicting the functional consequences of genetic variants in non-coding regions is a challenging problem. We propose here a semi-supervised approach, GenoNet, to jointly utilize experimentally confirmed regulatory variants (labeled variants), millions of unlabeled variants genome-wide, and more than a thousand cell/tissue type specific epigenetic annotations to predict functional consequences of non-coding variants. Through the application to several experimental datasets, we demonstrate that the proposed method significantly improves prediction accuracy compared to existing functional prediction methods at the tissue/cell type level, but especially so at the organism level. Importantly, we illustrate how the GenoNet scores can help in fine-mapping at GWAS loci, and in the discovery of disease associated genes in sequencing studies. As more comprehensive lists of experimentally validated variants become available over the next few years, semi-supervised methods like GenoNet can be used to provide increasingly accurate functional predictions for variants genome-wide and across a variety of cell/tissue types.
Induction of immunosuppressive functions and NF-κB by FLIP in monocytes
Authors: Fiore Alessandra , Ugel Stefano , De Sanctis Francesco , Sandri Sara , Fracasso Giulio , Trovato Rosalinda , Sartoris Silvia , Solito Samantha , Mandruzzato Susanna , Vascotto Fulvia , Hippen Keli L. , Mondanelli Giada , Grohmann Ursula , Piro Geny , Carbone Carmine , Melisi Davide , Lawlor Rita T. , Scarpa Aldo , Lamolinara Alessia , Iezzi Manuela , Fassan Matteo , Bicciato Silvio , Blazar Bruce R. , Sahin Ugur , Murray Peter J. , Bronte Vincenzo
Published: November 2018

Immunosuppression is a hallmark of tumor progression, and treatments that inhibit or deplete monocytic myeloid-derived suppressive cells could promote anti-tumor immunity. c-FLIP is a central regulator of caspase-8-mediated apoptosis and necroptosis. Here we show that low-dose cytotoxic chemotherapy agents cause apoptosis linked to c-FLIP down-regulation selectively in monocytes. Enforced expression of c-FLIP or viral FLIP rescues monocytes from cytotoxicity and concurrently induces potent immunosuppressive activity, in T cell cultures and in vivo models of tumor progression and immunotherapy. FLIP-transduced human blood monocytes can suppress graft versus host disease. Neither expression of FLIP in granulocytes nor expression of other anti-apoptotic genes in monocytes conferred immunosuppression, suggesting that FLIP effects on immunosuppression are specific to monocytic lineage and distinct from death inhibition. Mechanistically, FLIP controls a broad transcriptional program, partially by NF-κB activation. Therefore, modulation of FLIP in monocytes offers a means to elicit or block immunosuppressive myeloid cells.
Calponin-3 is critical for coordinated contractility of actin stress fibers
Authors: Ciuba Katarzyna , Hawkes William , Tojkander Sari , Kogan Konstantin , Engel Ulrike , Iskratsch Thomas , Lappalainen Pekka
Published: November 2018

Contractile actomyosin bundles, stress fibers, contribute to morphogenesis, migration, and mechanosensing of non-muscle cells. In addition to actin and non-muscle myosin II (NMII), stress fibers contain a large array of proteins that control their assembly, turnover, and contractility. Calponin-3 (Cnn3) is an actin-binding protein that associates with stress fibers. However, whether Cnn3 promotes stress fiber assembly, or serves as either a positive or negative regulator of their contractility has remained obscure. Here, we applied U2OS osteosarcoma cells as a model system to study the function of Cnn3. We show that Cnn3 localizes to both NMII-containing contractile ventral stress fibers and transverse arcs, as well as to non-contractile dorsal stress fibers that do not contain NMII. Fluorescence-recovery-after-photobleaching experiments revealed that Cnn3 is a dynamic component of stress fibers. Importantly, CRISPR/Cas9 knockout and RNAi knockdown studies demonstrated that Cnn3 is not essential for stress fiber assembly. However, Cnn3 depletion resulted in increased and uncoordinated contractility of stress fibers that often led to breakage of individual actomyosin bundles within the stress fiber network. Collectively these results provide evidence that Cnn3 is dispensable for the assembly of actomyosin bundles, but that it is required for controlling proper contractility of the stress fiber network.
Graphene nanoplatelets as nanofillers in mesoporous silicon oxycarbide polymer derived ceramics
Authors: Sujith Ravindran , Chauhan Pawan Kumar , Gangadhar Jella , Maheshwari Ankur
Published: November 2018

Understanding the role of graphene in the thermal stability and pore morphology of polymer derived silicon oxycarbide is crucial for electrochemical energy storage and hydrogen storage applications. Here in this work, we report the synthesis of graphene nanoplatelets dispersed silicon oxycarbide ceramics by the polymer to ceramic synthesis route. Samples containing graphene and without graphene are subjected to different pyrolysis conditions and are characterized using FT-IR, XPS, Raman spectroscopy, XRD, FE-SEM, HR-TEM, and BET. The results show that the graphene dispersed in the ceramic has undergone structural distortions upon pyrolysis and resulted in the formation of nanoclusters of graphene and turbostratic graphene. The XRD results confirm that with the incorporation of higher wt.% of GNP there is resistance to crystallization even at an exceedingly high pyrolysis temperature. The pores are bimodal in nature with specific surface area ranging between 22 and 70 m2/g and are generated in-situ during the polymer to ceramic conversion. Our study confirms that upon adjusting the graphene content it is possible to tune the structure and pore morphology of the polymer derived ceramics as per the requirements.
Generation of a highly efficient and tissue-specific tryptophan hydroxylase 1 knockout mouse model
Authors: Kim Hyeongseok , Kim Yeong Gi , Choi Wonsuk , Moon Joon Ho , Hwang Inseon , Kim Kyuho , Yadav Vijay K. , Karsenty Gerard , Jeong Ji-Seon , Kim Hail
Published: November 2018

Recent studies on tissue-autonomous serotonin (5-hydroxytryptamine [5-HT]) function have identified new roles for 5-HT in peripheral organs. Most of these studies were performed by crossing mice carrying the Tph1tm1Kry allele with tissue specific Cre mice. In the present study, we found that 5-HT production was not completely abolished in Tph1tm1Kry KO mice. The residual 5-HT production in Tph1tm1Kry KO mice is attributed to the expression of a truncated form of TPH1 containing the catalytic domain. Hence, in an effort to obtain mice with a Tph1 null phenotype, we generated mice harboring a new Tph1 floxed allele, Tph1tm1c, targeting exons 5 and 6 which encode the catalytic domain of TPH1. By crossing the new Tph1 floxed mice with villin-Cre or insulin-Cre mice, we observed near-complete ablation of 5-HT production in the intestine and β cells. In conclusion, this improved Tph1 floxed mouse model will serve as useful and accurate tool for analyzing peripheral 5-HT system.
Stable factor structure of the Edinburgh Postnatal Depression Scale during the whole peripartum period: Results from a Japanese prospective cohort study
Authors: Kubota Chika , Inada Toshiya , Nakamura Yukako , Shiino Tomoko , Ando Masahiko , Aleksic Branko , Yamauchi Aya , Morikawa Mako , Okada Takashi , Ohara Masako , Sato Maya , Murase Satomi , Goto Setsuko , Kanai Atsuko , Ozaki Norio
Published: November 2018

Early detection of perinatal depression is an urgent issue. Our study aimed to examine the construct validity and factor structure of the Japanese version of the Edinburgh Postnatal Depression Scale (EPDS) from a prospective cohort study from pregnancy to postpartum. A total of 1075 women completed all items of the EPDS at four time points: early pregnancy, late pregnancy, 5 days postpartum and 1 month postpartum. The participants were randomly divided into two sample sets. The first sample set (n = 304) was used for exploratory factor analysis, and the second sample set (n = 771) was used for confirmatory factor analysis. As a result, the Cronbach’s alpha coefficients of the EPDS items were 0.762, 0.740, 0.765 and 0.772 at the four time points. From the confirmatory factor analysis of the EPDS in a sample set of Japanese women from pregnancy to postpartum, the following three factors were detected: depression (items 7, 9), anxiety (items 4, 5) and anhedonia (items 1, 2). In conclusion, the EPDS is a useful rating scale, and its factor structure is consistently stable during the whole peripartum period.
A critical review of anthropological studies on skeletons from European plague pits of different epochs
Authors: Bramanti B. , Zedda N. , Rinaldo N. , Gualdi-Russo E.
Published: November 2018

In historical times, plague epidemics intermittently ravaged Europe for more than 1,400 years, and still represent a threat in many countries all over the world. A debate is ongoing about the past plague, if it killed randomly in a population or discriminated among persons on the basis of their biological features. To address questions of plague lethality, we reviewed a large number of anthropological studies published in the last twenty years on victims of the past pestilences in Europe. In particular, we focused on data concerning demography (age at death and sex determination), and health status (skeletal biomarkers). We applied to these data a model system based on Multiple Linear Regression, which aimed to discern among possible predictors of sex-selective plague lethality in entire populations, in different periods and regions. Based on available data, we lack evidence for general trends of association between biological features. Differences in sex ratio are more likely due to the original population compositions or to distinct cultural behaviours of the two genders. We concluded that generalizations on biological evidence are not feasible for ancient plagues if we exclude that the infection possibly killed primarily persons between 5–10 and 20–35 years of age.
External temperature control of lymphatic drainage of thermo-sensitive nanomaterials
Authors: Zhang Mingming , Chen Wenjuan , Hong Yanhang , Chen Han , Wang Chun
Published: November 2018

External temperature control actively modulated the biodistribution of a thermo-sensitive nanomaterial among the injection site and the draining LNs.
Towards rapid prediction of drug-resistant cancer cell phenotypes: single cell mass spectrometry combined with machine learning
Authors: Liu Renmeng , Zhang Genwei , Yang Zhibo
Published: November 2018

The combination of single cell mass spectrometry with machine learning enables prediction of drug-resistant cell phenotypes based on metabolomic profiles.
Fe3O4–ZIF-8 assemblies as pH and glutathione responsive T2–T1 switching magnetic resonance imaging contrast agent for sensitive tumor imaging in vivo
Authors: Lin Jiaomin , Xin Pengyan , An Lu , Xu Yanjun , Tao Cheng , Tian Qiwei , Zhou Zhiguo , Hu Bing , Yang Shiping
Published: November 2018

Fe3O4 nanoparticles were assembled into a zeolitic-imidazole framework to form a pH- and glutathione-responsive T2–T1 switching contrast agent for sensitive tumor imaging.
Zr-MOF-808@MCM-41 catalyzed phosgene-free synthesis of polyurethane precursors
Authors: Rojas-Buzo Sergio , García-García Pilar , Corma Avelino
Published: November 2018

Zr-MOF-808@MCM-41 exhibited high catalytic activity, selectivity and stability for the synthesis of aromatic carbamates from aromatic amines and dimethyl carbonate.
Consumption of sheep milk compared to cow milk can affect trabecular bone ultrastructure in a rat model
Authors: Burrow Keegan , Young Wayne , Carne Alan , McConnell Michelle , Hammer Niels , Scholze Mario , Bekhit Alaa El-Din
Published: November 2018

Sheep milk contains a higher nutrient content compared to cow milk and is able to improve the structure of bone.
An expeditious synthetic route to proteomimetic foldamers
Authors: Karekar Vaibhav V. , Bhoge Bapurao A. , Saraogi Ishu
Published: November 2018

We report a method for rapid generation of an α-helix proteomimetic libraryviathe late stage modification of a protected oligobenzamide intermediate.
Scalable, large-area synthesis of heteroatom-doped few-layer graphene-like microporous carbon nanosheets from biomass for high-capacitance supercapacitors
Authors: Gopalakrishnan Arthi , Kong Chang Yi , Badhulika Sushmee
Published: November 2018

Ginger-derived biomass ultrathin graphene-like carbon nanosheets for supercapacitor applications
Synthetic approaches to natural products containing 2,3-dihydrobenzofuran skeleton
Authors: Chen Zhuang , Pitchakuntla Mallesham , Jia Yanxing
Published: November 2018

This review describes the synthetic approaches to natural products containing the 2,3-dihydrobenzofuran (2,3-DHB) skeleton.
In situ regulating aspect ratio of bamboo-like CNTs via CoxNi1−x-catalyzed growth to pursue superior microwave attenuation in X-band
Authors: Cheng Yan , Cao Jieming , Lv Hualiang , Zhao Huanqin , Zhao Yue , Ji Guangbin
Published: November 2018

Controlling aspect ratios of bamboo-like CNTs to achieve superior microwave absorption performance in X-band.
A stable zinc–organic framework with luminescence detection of acetylacetone in aqueous solution
Authors: Kang Xiao-Min , Fan Xi-Yu , Hao Peng-Yuan , Wang Wen-Min , Zhao Bin
Published: November 2018

A stable Zn-based MOF has been prepared, presenting the first example of a recyclable luminescent sensor for recognizing acetylacetone in aqueous solution.
Effect of double mutations T790M/L858R on conformation and drug-resistant mechanism of epidermal growth factor receptor explored by molecular dynamics simulations
Authors: Yan Fangfang , Liu Xinguo , Zhang Shaolong , Su Jing , Zhang Qinggang , Chen Jianzhong
Published: November 2018

The MM-GBSA method coupled with residue-based free energy decomposition method was performed to explore drug-resistant mechanisms of the mutated EGFR.
Interactions of a paracyclophane-based conjugated oligoelectrolyte with biological membranes
Authors: Limwongyut Jakkarin , Liu Yang , Chilambi Gayatri Shankar , Seviour Thomas , Hinks Jamie , Mu Yuguang , Bazan Guillermo C.
Published: November 2018

We report a non-planar conjugated oligoelectrolyte as a membrane permeabilizing material and its membrane interactions compared to the linear analog.
Amplified circularly polarized phosphorescence from co-assemblies of platinum(ii) complexes
Authors: Park Gyurim , Kim Hyungchae , Yang Hoichang , Park Kyung Ryoul , Song Inho , Oh Joon Hak , Kim Changsoon , You Youngmin
Published: November 2018

Co-assemblies of platinum(ii) complexes produce amplified circularly polarized phosphorescence emission.
Dual defect system of tellurium antisites and silver interstitials in off-stoichiometric Bi2(Te,Se)3+ycausing enhanced thermoelectric performance
Authors: Kim Cham , Lopez David Humberto , Kim Dong Hwan , Kim Hoyoung
Published: November 2018

Thermoelectric performance was significantly enhanced with off-stoichiometric Bi2(Te,Se)3+yhaving the dual defect system of Te antisites and Ag interstitials.
Metal-doped carbon nanoparticles with intrinsic peroxidase-like activity for colorimetric detection of H2O2 and glucose
Authors: Bao Yan-Wen , Hua Xian-Wu , Ran Huan-Huan , Zeng Jia , Wu Fu-Gen
Published: November 2018

We develop a general hydrothermal approach to fabricate new nanozymes with intrinsic peroxidase-like activity for H2O2 and glucose detection.
Peroxidase-like activity of acetylcholine-based colorimetric detection of acetylcholinesterase activity and an organophosphorus inhibitor
Authors: Han Ting , Wang Guangfeng
Published: November 2018

Colorimetric detection of acetylcholinesterase (AChE) and its inhibitor organophosphates (OPs) is attractive for its convenience, but the addition of exogenous catalyst to produce a chromogenic agent may result in complexity and interference.
Design of dual drug-loaded dendrimer/carbon dot nanohybrids for fluorescence imaging and enhanced chemotherapy of cancer cells
Authors: Li Dan , Fan Yu , Shen Mingwu , Bányai István , Shi Xiangyang
Published: November 2018

Dual drug-loaded dendrimer/CD nanohybrids can be developed for fluorescence imaging and enhanced chemotherapy of cancer cells.
Advanced electronic skin devices for healthcare applications
Authors: Ma Zhong , Li Sheng , Wang Huiting , Cheng Wen , Li Yun , Pan Lijia , Shi Yi
Published: November 2018

This review summarized recent progress in skin-inspired electronic devices and their applications in human health monitoring and therapy systems.
Photochromism of aminobenzopyrano-xanthene with different fluorescent behavior in solution and the crystal state
Authors: Ma Zhiyong , Li Aisen , Huang Lili , Qiu Yixin , Xu Shuping , Xu Weiqing , Jia Xinru
Published: November 2018

Herein, we report the unique photochromic properties of aminobenzopyrano-xanthene (named cis- and trans-RhRh) with different fluorescence behavior in solution and the crystal state.
Water-stable organic field-effect transistors based on naphthodithieno[3,2-b]thiophene derivatives
Authors: Li Chenyu , Zhang Ji , Li Zhaoguang , Zhang Weifeng , Wong Man Shing , Yu Gui
Published: November 2018

Water-stable organic field-effect transistors based on naphthodithieno[3,2-b]thiophene derivatives were fabricated and the possible mechanism for high water stability was proposed.
High-efficiency non-fullerene polymer solar cell fabricated by a simple process using new conjugated terpolymers
Authors: Hoang Mai Ha , Park Gi Eun , Choi Suna , Park Chang Geun , Park Su Hong , Nguyen Tuyen Van , Kim Sangjun , Kwak Kyungwon , Cho Min Ju , Choi Dong Hoon
Published: November 2018

A series of conjugated terpolymers bearing weak and strong accepting units were synthesized. Their optical and electrochemical properties and device performance can be easily tuned by controlling molar ratio of two accepting units.
Optimierungsansätze für stationäre Apotheken vor dem
Hintergrund der Kundenerwartungen und deren Erfüllung
Authors: Godbersen Hendrik , Kaupp Fiona
Published: November 2018

Ziel der Studie Vor dem Hintergrund eines gewachsenen Konkurrenzdrucks
durch Drogerien und Online-Apotheken und der heilberuflichen Verpflichtung von
stationären Apotheken ist es das Ziel der vorliegenden Untersuchung, die
Kundenerwartungen und deren Erfüllung differenziert abzubilden, um daraus
Optimierungsansätze für Apotheken zu entwickeln.

Methodik Die inhaltliche Grundlage für die Studie bildet ein
hierarchisches Beurteilungsmodell von Apotheken, das aus den Ebenen Apotheke
insgesamt, Apothekenleistungen und Qualitätseigenschaften von Apotheken besteht.
Zur Messung wird die Means-End Theory of Complex Cognitive Structures
herangezogen. Es wurden 293 Apothekenkunden befragt.

Ergebnisse Den Kunden sind die „klassischen“ Apothekenleistungen
Arzneimitteldistribution und Beratung, und die damit zusammenhängenden
Qualitätseigenschaften wichtiger als Extra-Services. Die stationären Apotheken
erfüllen die Erwartungen der Kunden in den beiden erstgenannten Bereichen mit
Ausnahme der Online-Bestellfunktion zu ca. 70 %, wohingegen die Extra-Services
eine Erwartungserfüllung von unter 50 % erreichen.

Schlussfolgerungen Auf der Grundlage der empirischen Ergebnisse sollten
sich stationäre Apotheken als erstes auf ihre Kernaufgaben konzentrieren und die
Qualität der Arzneimitteldistribution und Kundenberatung sichern und ausbauen.
Mit zweiter Priorität sollte die Qualität der Extra-Services aufgebaut
werden.
Use of Metformin and Platelet Reactivity in Diabetic Patients Treated with Dual Antiplatelet Therapy
Authors: Verdoia Monica , Pergolini Patrizia , Rolla Roberta , Ceccon Claudia , Caputo Marina , Aimaretti Gianluca , Suryapranata Harry , De Luca Giuseppe
Published: November 2018

Background Enhanced platelet reactivity represents one of the major determinants of cardiovascular risk among diabetic patients. The aim of the present study was to evaluate the impact of metformin use on platelet reactivity in diabetic patients receiving dual antiplatelet therapy (DAPT).

Methods We included diabetic patients treated with DAPT after an acute coronary syndrome or percutaneous coronary intervention. Platelet reactivity was assessed at 30–90 days by Multiple-electrode aggregometry. In an additional cohort of diabetic patients naïve to antiplatelet therapy, we assessed platelet reactivity by light transmission aggregometry, surface expression of P-selectin and plasma concentration of Thromboxane B2 (TxB2).

Results We included 219 diabetic patients, 117 (53.4%) treated with metformin. Metformin was associated with younger age (p=0.03), male gender (p=0.02), lower rate of hypertension (p=0.04), active smoker (p=0.002), previous MI (p<0.001) renal failure (p<0.001), fibrinogen (p<0.001) and C-reactive protein (p=0.04), larger use of diuretics (p=0.04) calcium antagonists (p=0.05), better glycemic control (p<0.001) and higher haemoglobin (p=0.003). The prevalence of HAPR did not significantly differ according to hypoglycemic treatment (p=0.73; adjusted OR[95%CI]=5.63[0.42-76], p=0.19). Moreover, no impact of metformin was observed for HRPR (p=0.77; adjusted OR[95%CI]=1.15[0.55-2.4], p=0.71). Among an additional cohort of 42 diabetic patients naïve to antiplatelet therapy, we confirmed no impact of metformin or insulin on aggregation.

Conclusions Our study found no apparent association in diabetic patients treated with DAPT, between the use of metformin and platelet reactivity or the rate of HPR.
Predictors of Outcome for Aortic Valve Reimplantation Including the Surgeon—A Single-Center Experience
Authors: Tkebuchava Sophie , Tasar Raphael , Lehmann Thomas , Faerber Gloria , Diab Mahmoud , Breuer Martin , Franke Ulrich , Kirov Hristo , Gummert Jan , Lichtenberg Artur , Wahlers Thorsten , Doenst Torsten
Published: November 2018

Introduction Aortic valve reimplantation is considered technically demanding. We searched for predictors of long-term outcome including the surgeon as risk factor.

Methods We selected all aortic valve reimplantations performed in our department between December 1999 and January 2017 and obtained a complete follow-up. The main indications were combined aortic aneurysm plus aortic valve regurgitation (AR), 69% and aortic dissections (15%). In 14%, valves were bicuspid. Cusp repair was performed in 27% of patients. One-third received additional procedures (coronary artery bypass grafting, mitral, or arch surgery). We performed multivariable analyses for independent risk factors of short- and long-term outcomes, including “surgeon” as variable. Twelve different surgeons operated on 193 patients. We created three groups: surgeons A and B with 84 and 64 procedures, respectively, and surgeon C (10 surgeons for 45 patients).

Results Cardiopulmonary bypass and clamp times were 176 ± 45 and 130 ± 24 minutes, respectively. In-hospital mortality was 2%. Postoperatively, 5% had mild and 0.5% had moderate AR. Kaplan–Meier's survival estimates, freedom from reoperation, and freedom from severe AR at 12 years were 97 ± 1, 93 ± 2, and 91 ± 3%, respectively. Age and chronic obstructive pulmonary disease appeared as risk factors for perioperative complications by univariate analysis. Age, coronary artery disease, and duration of cardiopulmonary bypass, but not surgeon, presented as risk factors by multivariable analysis.

Conclusion The results suggest that if a David procedure is performed successfully, long-term durability may be excellent. They also suggest that good and durable results are possible even with limited experience of the operating surgeon.
Maternal and Fetal Outcomes in Pregnancies affected by Bone and Soft Tissue Tumors
Authors: Figueiro-Filho Ernesto , Al-Sum Hythem , Parrish Jacqueline , Wunder Jay , Maxwell Cynthia
Published: November 2018

Objective This study was aimed to describe perinatal outcome of a cohort of pregnant patients with bone and soft tissue tumors and to compare the current series with our group's previously reported experience.

Methods Pregnant women diagnosed before and during pregnancy were identified, retrospectively, for the years 2004 to 2014. Relevant maternal and neonatal data were collected.

Results Forty-eight patients were identified. Ten cases were diagnosed during pregnancy. Pelvis, abdomen, and extremities were the most common tumor locations. Osteosarcoma, liposarcoma, and Ewing's sarcoma were the most common histological types and comprise more than 50% of the cases. Metastases occurred in nine cases. Most of the cases (60%) were treated surgically during pregnancy and delivery occurred at term. Chemotherapy was delayed until after delivery. There were no perinatal or infant deaths. Patients presented with advanced maternal disease in 18% in previous report (1983–2003) versus 40% in present report (2004–2014). Metastases were present in 40% and maternal death rate was approximately 20% in both cohorts.

Conclusion Pregnant women with bone and soft tissue tumors are candidates for standard surgical management during pregnancy. Other treatments, such as chemotherapy and radiotherapy must be evaluated for each woman on a case-by-case basis. Iatrogenic prematurity was common in our findings.
Going global: the adoption of the World Health Organization’s enabling recommendation on oral pre-exposure prophylaxis for HIV
Authors: Hodges-Mameletzis Ioannis , Dalal Shona , Msimanga-Radebe Busisiwe , Rodolph Michelle , Baggaley Rachel
Published: November 2018

In September 2015, the World Health Organization (WHO) launched evidence-based guidelines by recommending that any person at substantial HIV risk should be offered oral pre-exposure prophylaxis (PrEP) containing tenofovir disoproxil fumarate (TDF) as an additional prevention choice. Since 2017, PrEP medicines have also been listed in the WHO’s Essential Medicines List, including TDF/emtricitabine (FTC) and TDF in combination with lamivudine (3TC). A descriptive policy review and analysis of countries adopting WHO’s 2015 recommendation on oral PrEP was conducted. As of June 2018, we identified 35 countries that had some type of policy on oral PrEP, and an additional five countries where a specific policy on PrEP is currently pending. A total of 19 high-income countries (HICs) and 21 low- and middle-income countries (LMICs) have adopted or have a pending policy. Most countries that have adopted or pending PrEP are in the European (42.9%) or African (30.0%) region. TDF/FTC is the most commonly recommended PrEP drug in the guidelines reviewed, although seven countries, namely in sub-Saharan Africa (6/7), are also recommending the use of TDF/3TC for PrEP. In sum, by the end of 2018, at least 40 countries (20.6%) are anticipated to have adopted WHO’s oral PrEP recommendation. Nonetheless, policy uptake does not reflect broader programmatic coverage of PrEP services, which remain limited across all settings, irrespective of income status. Enhancing global partnerships is needed to support and track ongoing policy adoption and to ensure that policy is translated into meaningful implementation of PrEP services.
Cancer-associated fibroblasts suppress SOX2-induced dysplasia in a lung squamous cancer coculture
Authors: Chen Shuang , Giannakou Andreas , Wyman Sarah , Gruzas Janet , Golas Jonathon , Zhong Wenyan , Loreth Christine , Sridharan Latha , Yamin Ting-Ting , Damelin Marc , Geles Kenneth G.
Published: November 2018

Tumorigenesis depends on intricate interactions between genetically altered tumor cells and their surrounding microenvironment. While oncogenic drivers in lung squamous carcinoma (LUSC) have been described, the role of stroma in modulating tissue architecture, particularly cell polarity, remains unclear. Here, we report the establishment of a 3D coculture system of LUSC epithelial cells with cancer-associated fibroblasts (CAFs) and extracellular matrix that together capture key components of the tumor microenvironment (TME). Single LUSC epithelial cells develop into acinar-like structures with 0.02% efficiency, and addition of CAFs provides proper tumor−stromal interactions within an appropriate 3D architectural context. Using this model, we recapitulate key pathological changes during tumorigenesis, from hyperplasia to dysplasia and eventually invasion, in malignant LUSC spheroids that undergo phenotypic switching in response to cell intrinsic and extrinsic changes. Overexpression of SOX2 is sufficient to mediate the transition from hyperplasia to dysplasia in LUSC spheroids, while the presence of CAFs makes them invasive. Unexpectedly, CAFs suppress the activity of high SOX2 levels, restore hyperplasia, and enhance the formation of acinar-like structures. Taken together, these observations suggest that stromal factors can override cell intrinsic oncogenic changes in determining the disease phenotype, thus providing fundamental evidence for the existence of dynamic reciprocity between the nucleus and the TME of LUSC.
The adult oligodendrocyte can participate in remyelination
Authors: Duncan Ian D. , Radcliff Abigail B. , Heidari Moones , Kidd Grahame , August Benjamin K. , Wierenga Lauren A.
Published: November 2018

Significance

Remyelination of the CNS is a critical process in restoring function and protecting nerve fibers from degeneration in multiple sclerosis and other demyelinating diseases. It is currently thought that myelin can only be repaired by the generation of new oligodendrocytes from progenitor cells and that remaining mature cells are unable to participate. Here we show, using unique large animal models, including a nonhuman primate, that oligodendrocytes that are partially injured can participate in myelin repair. The capacity of mature oligodendrocytes to remyelinate in demyelinating disease remains unknown, yet it provides an additional cell source for recruitment for myelin repair.
Grammar is community-specific
Authors: Höder Steffen
Published: November 2018

Mainstream grammatical theory and traditional grammaticography concentrate on single languages or varieties, which are conceptualised as pre-existing, distinct entities and analysed in terms of coherent, static, ideally variation-free language systems. This is in stark contrast to actual language usage, where various kinds of structural contact phenomena are the rule rather than the exception. In line with recent insights from contact linguistics, Diasystematic Construction Grammar assumes that multilingual speakers and communities organise their grammatical knowledge on the basis of the available input via processes of interlingual identification, abstraction, generalisation, and categorisation, regardless of language boundaries. This results in a community-specific multilingual constructicon, comprising both language-specific constructions (restricted to certain communicative contexts associated with a particular language) and constructions unspecified for language.
The syntactic status of by-phrases in Korean and Japanese
Authors: Park Sang Doh
Published: November 2018

Traditional analyses of Japanese syntax make a distinction between ni passives and ni yotte passives depending on the type of by-phrases. These two patterns of passives correspond semantically to HI passives and CI passives in Korean respectively in that the subject in ni passives and HI passives typically bears an Affectee role whereas the subject in ni yotte passives and CI passives is not constrained by this semantic requirement. Despite the superficial similarities between Japanese and Korean passives, however, the by-phrases behave like arguments in both types of Korean passives whereas their Japanese counterparts demonstrate adjunct-like properties in ni yotte passives. While unveiling what mechanism operates in generating each type of passive construction, this chapter investigates the syntactic status of by-phrases and the origin that triggers the affectedness constraint observed in these East Asian languages.
Resultative and termination
Authors: Aldridge Edith , Meisterernst Barbara
Published: November 2018

This paper proposes an account of the reanalysis of the Chinese morpheme 已yǐ from an intransitive verb meaning ‘end, terminate’ into a functional category marking completive aspect. We posit that this grammaticalization was triggered by the loss of aspectual affixes, prompting YI to be reinterpreted from a lexical verb to a secondary predicate supplying the endpoint to an event expressed by a preceding predicate. The use of YI as a secondary predicate was made possible in part by changes in Chinese VP structure which allowed an endpoint-denoting secondary predicate to occupy a VP-internal position in this period.
Quantitative and qualitative restrictions on the distribution of lexical tones in Thai
Authors: Pittayaporn Pittayawat
Published: November 2018

In present-day Thai, contour tones show a more restricted distribution in comparison with level tones that cannot be explained by syllable structure alone. This diachronic study argues that both quantitative and qualitative restrictions are responsible for the puzzling gaps and accounts for them by positing Optimality-Theoretic constraints. In addition, it analyzes the tonal distribution in the early 19th and 20th centuries based on data from published materials. Furthermore, it discusses sound changes and lexical changes that gave rise to the tonal distribution.
Cardiorespiratory and perceptual responses of two interval training and a continuous training protocol in healthy young men
Authors: Naves João Pedro Araújo , Rebelo Ana Cristina Silva , Silva Lucas Raphael Bento E , Silva Maria Sebastiana , Ramirez‐Campillo Rodrigo , Ramírez‐Vélez Robinson , Gentil Paulo
Published: November 2018

High Intensity Interval Training (HIIT) can be performed with different effort to rest time‐configurations, and this can largely influence training responses. The purpose of the study was to compare the acute physiological responses of two HIIT and one moderate intensity continuous training (MICT) protocol in young men. A randomised cross‐over study with 10 men [age, 28.3 ± 5.5years; weight, 77.3 ± 9.3 kg; height, 1.8 ± 0.1 m; peak oxygen consumption (VO2peak), 44 ± 11 mL.kg−1.min−1]. Participants performed a cardiorespiratory test on a treadmill to assess VO2peak, velocity associated with VO2peak (vVO2peak), peak heart rate (HRpeak) and perceived exertion (RPE). Then participants performed three protocols equated by distance: Short HIIT (29 bouts of 30s at vVO2peak, interspersed by 30s of passive recovery, 29 min in total), Long HIIT (3 bouts of 4 min at 90% of vVO2peak, interspersed by 3 min of recovery at 60% of vVO2peak, 21 min in total) and MICT (21 min at 70% of vVO2peak). The protocols were performed in a randomised order with ≥48 h between them. VO2, HRpeak and RPE were compared. VO2peak in Long HIIT was significantly higher than Short HIIT and MICT (43 ± 11 vs 32 ± 8 and 37 ± 8 mL.kg−1.min−1, respectively, P < 0.05), as well as peak HR (181 ± 10 vs 168 ± 8 and 167 ± 11, respectively, P < 0.05), and RPE (17 ± 4 vs 14 ± 4 and 15 ± 4, respectively, P < 0.05), with no difference between Short HIIT and MICT. In conclusion, Long HIIT promoted higher acute increases in VO2, HR and RPE than Short HIIT and MICT, suggesting a higher demand on the cardiorespiratory system. Short HIIT and MICT presented similar physiologic and perceptual responses, despite Short HIIT being performed at higher velocities.
Loss of human ICOSL results in combined immunodeficiency
Authors: Roussel Lucie , Landekic Marija , Golizeh Makan , Gavino Christina , Zhong Ming-Chao , Chen Jun , Faubert Denis , Blanchet-Cohen Alexis , Dansereau Luc , Parent Marc-Antoine , Marin Sonia , Luo Julia , Le Catherine , Ford Brinley R. , Langelier Mélanie , King Irah L. , Divangahi Maziar , Foulkes William D. , Veillette André , Vinh Donald C.
Published: November 2018

Primary immunodeficiencies represent naturally occurring experimental models to decipher human immunobiology. We report a patient with combined immunodeficiency, marked by recurrent respiratory tract and DNA-based viral infections, hypogammaglobulinemia, and panlymphopenia. He also developed moderate neutropenia but without prototypical pyogenic infections. Using whole-exome sequencing, we identified a homozygous mutation in the inducible T cell costimulator ligand gene (ICOSLG; c.657C>G; p.N219K). Whereas WT ICOSL is expressed at the cell surface, the ICOSLN219K mutation abrogates surface localization: mutant protein is retained in the endoplasmic reticulum/Golgi apparatus, which is predicted to result from deleterious conformational and biochemical changes. ICOSLN219K diminished B cell costimulation of T cells, providing a compelling basis for the observed defect in antibody and memory B cell generation. Interestingly, ICOSLN219K also impaired migration of lymphocytes and neutrophils across endothelial cells, which normally express ICOSL. These defects likely contributed to the altered adaptive immunity and neutropenia observed in the patient, respectively. Our study identifies human ICOSLG deficiency as a novel cause of a combined immunodeficiency.
Cadmium opens GluK2 kainate receptors with cysteine substitutions at the M3 helix bundle crossing
Authors: Wilding Timothy J. , Huettner James E.
Published: November 2018

Kainate receptors are ligand-gated ion channels that have two major roles in the central nervous system: they mediate a postsynaptic component of excitatory neurotransmission at some glutamatergic synapses and modulate transmitter release at both excitatory and inhibitory synapses. Accumulating evidence implicates kainate receptors in a variety of neuropathologies, including epilepsy, psychiatric disorders, developmental delay, and cognitive impairment. Here, to gain a deeper understanding of the conformational changes associated with agonist binding and channel opening, we generate a series of Cys substitutions in the GluK2 kainate receptor subunit, focusing on the M3 helices that line the ion pore and form the bundle-crossing gate at the extracellular mouth of the channel. Exposure to 50 µM Cd produces direct activation of homomeric mutant channels bearing Cys substitutions in (A657C), or adjacent to (L659C), the conserved SYTANLAAF motif. Activation by Cd is occluded by modification with 2-aminoethyl MTS (MTSEA), indicating that Cd binds directly and specifically to the substituted cysteines. Cd potency for the A657C mutation (EC50 = 10 µM) suggests that binding involves at least two coordinating residues, whereas weaker Cd potency for L659C (EC50 = 2 mM) implies that activation does not require tight coordination by multiple side chains for this substitution. Experiments with heteromeric and chimeric channels indicate that activation by Cd requires Cys substitution at only two of the four subunits within a tetrameric receptor and that activation is similar for substitution within subunits in either the A/C or B/D conformations. We develop simple kinetic models for the A657C substitution that reproduce several features of Cd activation as well as the low-affinity inhibition observed at higher Cd concentrations (5–20 mM). Together, these results demonstrate rapid and reversible channel activation, independent of agonist site occupancy, upon Cd binding to Cys side chains at two specific locations along the GluK2 inner helix.
Computational functional genomics-based reduction of disease-related gene sets to their key components
Authors: Lippmann Catharina , Ultsch Alfred , Lötsch Jörn
Published: November 2018

Motivation

The genetic architecture of diseases becomes increasingly known. This raises difficulties in picking suitable targets for further research among an increasing number of candidates. Although expression based methods of gene set reduction are applied to laboratory-derived genetic data, the analysis of topical sets of genes gathered from knowledge bases requires a modified approach as no quantitative information about gene expression is available.

Results

We propose a computational functional genomics-based approach at reducing sets of genes to the most relevant items based on the importance of the gene within the polyhierarchy of biological processes characterizing the disease. Knowledge bases about the biological roles of genes can provide a valid description of traits or diseases represented as a directed acyclic graph (DAG) picturing the polyhierarchy of disease relevant biological processes. The proposed method uses a gene importance score derived from the location of the gene-related biological processes in the DAG. It attempts to recreate the DAG and thereby, the roles of the original gene set, with the least number of genes in descending order of importance. This obtained precision and recall of over 70% to recreate the components of the DAG charactering the biological functions of n=540 genes relevant to pain with a subset of only the k=29 best-scoring genes.

Conclusions

A new method for reduction of gene sets is shown that is able to reproduce the biological processes in which the full gene set is involved by over 70%; however, by using only ∼5% of the original genes.

Availability and implementation

The necessary numerical parameters for the calculation of gene importance are implemented in the R package dbtORA at https://github.com/IME-TMP-FFM/dbtORA.

Supplementary information

Supplementary data are available at Bioinformatics online.
Utility of machine learning algorithms in assessing patients with a systemic right ventricle
Authors: Diller Gerhard-Paul , Babu-Narayan Sonya , Li Wei , Radojevic Jelena , Kempny Aleksander , Uebing Anselm , Dimopoulos Konstantinos , Baumgartner Helmut , Gatzoulis Michael A , Orwat Stefan
Published: November 2018

Aims

To investigate the utility of novel deep learning (DL) algorithms in recognizing transposition of the great arteries (TGA) after atrial switch procedure or congenitally corrected TGA (ccTGA) based on routine transthoracic echocardiograms. In addition, the ability of DL algorithms for delineation and segmentation of the systemic ventricle was evaluated.

Methods and results

In total, 132 patients (92 TGA and atrial switch and 40 with ccTGA; 60% male, age 38.3 ± 12.1 years) and 67 normal controls (57% male, age 48.5 ± 17.9 years) with routine transthoracic examinations were included. Convolutional neural networks were trained to classify patients by underlying diagnosis and a U-Net design was used to automatically segment the systemic ventricle. Convolutional networks were build based on over 100 000 frames of an apical four-chamber or parasternal short-axis view to detect underlying diagnoses. The DL algorithm had an overall accuracy of 98.0% in detecting the correct diagnosis. The U-Net architecture model correctly identified the systemic ventricle in all individuals and achieved a high performance in segmenting the systemic right or left ventricle (Dice metric between 0.79 and 0.88 depending on diagnosis) when compared with human experts.

Conclusion

Our study demonstrates the potential of machine learning algorithms, trained on routine echocardiographic datasets to detect underlying diagnosis in complex congenital heart disease. Automated delineation of the ventricular area was also feasible. These methods may in future allow for the longitudinal, objective, and automated assessment of ventricular function.
The impact of mobile technology on teamwork and communication in hospitals: a systematic review
Authors: Martin Guy , Khajuria Ankur , Arora Sonal , King Dominic , Ashrafian Hutan , Darzi Ara
Published: November 2018

Objectives

Effective communication is critical to the safe delivery of care but is characterized by outdated technologies. Mobile technology has the potential to transform communication and teamwork but the evidence is currently uncertain. The objective of this systematic review was to summarize the quality and breadth of evidence for the impact of mobile technologies on communication and teamwork in hospitals.

Materials and Methods

Electronic databases (MEDLINE, PsycINFO, EMBASE, CINAHL Plus, HMIC, Cochrane Library, and National Institute of Health Research Health Technology Assessment) were searched for English language publications reporting communication- or teamwork-related outcomes from mobile technologies in the hospital setting between 2007 and 2017.

Results

We identified 38 publications originating from 30 studies. Only 11% were of high quality and none met best practice guidelines for mobile-technology-based trials. The studies reported a heterogenous range of quantitative, qualitative, and mixed-methods outcomes. There is a lack of high-quality evidence, but nonetheless mobile technology can lead to improvements in workflow, strengthen the quality and efficiency of communication, and enhance accessibility and interteam relationships.

Discussion

This review describes the potential benefits that mobile technology can deliver and that mobile technology is ubiquitous among healthcare professionals. Crucially, it highlights the paucity of high-quality evidence for its effectiveness and identifies common barriers to widespread uptake. Limitations include the limited number of participants and a wide variability in methods and reported outcomes.

Conclusion

Evidence suggests that mobile technology has the potential to significantly improve communication and teamwork in hospital provided key organizational, technological, and security challenges are tackled and better evidence delivered.