bluuebunny/crossref_metadata_2025_split huggingface dataset:
Blocking inflammation to improve immunotherapy of advanced cancer
Authors: Macciò Antonio , Madeddu Clelia 
Published: December 2019

AbstractThe ability to induce functional reprogramming of regulatory T (Treg) cells in the tumor microenvironment is an extremely important therapeutic opportunity. However, when discussing such an approach, the opposing effect that the activation of the Treg cell compartments may have in inducing the immune inflammatory response and its link with the efficacy of immunotherapy should be considered. In fact, Treg reprogramming has a dual effect: immediate, with mechanisms that activate immunosurveillance, and late, mediated by the macrophage activation that yields an inflammatory status that is deleterious for the antineoplastic efficiency of the immune system response. Persistence of the inflammatory response is associated with specific changes of oxidative and glycolytic metabolic pathways that interfere with conventional T‐cell activation and function and may be one of the reasons for the failure of immunotherapy in advanced cancer patients. Therefore, in addition to modulating Treg cell action, the combined use of drugs able to block chronic inflammation mediated mainly by macrophages, to counteract the oxidative stress, and to positively regulate the metabolic derangements, could improve the effectiveness of modern immunotherapy. In conclusion, reprogramming of Treg cells may be an appropriate strategy for treating early stages of neoplastic diseases, whereas other immunosuppressive mechanisms should be the target of a combined immunotherapy approach in more advanced phases of cancer.
Identification of dynamic signatures associated with smoking‐related squamous cell lung cancer and chronic obstructive pulmonary disease
Authors: Sun Xiaoru , Shang Jingzhe , Wu Aiping , Xia Jingyan , Xu Feng 
Published: December 2019

AbstractChronic obstructive pulmonary disease (COPD) is a risk factor for the development of lung cancer. The aim of this study was to identify early diagnosis biomarkers for lung squamous cell carcinoma (SQCC) in COPD patients and to determine the potential pathogenetic mechanisms. The GSE12472 data set was downloaded from the Gene Expression Omnibus database. Differentially co‐expressed links (DLs) and differentially expressed genes (DEGs) in both COPD and normal tissues, or in both SQCC + COPD and COPD samples were used to construct a dynamic network associated with high‐risk genes for the SQCC pathogenetic process. Enrichment analysis was performed based on Gene Ontology annotations and Kyoto Encyclopedia of Genes and Genomes pathway analysis. We used the gene expression data and the clinical information to identify the co‐expression modules based on weighted gene co‐expression network analysis (WGCNA). In total, 205 dynamic DEGs, 5034 DLs and one pathway including CDKN1A, TP53, RB1 and MYC were found to have correlations with the pathogenetic progress. The pathogenetic mechanisms shared by both SQCC and COPD are closely related to oxidative stress, the immune response and infection. WGCNA identified 11 co‐expression modules, where magenta and black were correlated with the “time to distant metastasis.” And the “surgery due to” was closely related to the brown and blue modules. In conclusion, a pathway that includes TP53, CDKN1A, RB1 and MYC may play a vital role in driving COPD towards SQCC. Inflammatory processes and the immune response participate in COPD‐related carcinogenesis.
Inhibition of bromodomain and extra‐terminal proteins increases sensitivity to venetoclax in chronic lymphocytic leukaemia
Authors: Carrà Giovanna , Nicoli Paolo , Lingua Marcello Francesco , Maffeo Beatrice , Cartellà Antonio , Circosta Paola , Brancaccio Mara , Parvis Guido , Gaidano Valentina , Guerrasio Angelo , Saglio Giuseppe , Taulli Riccardo , Morotti Alessandro 
Published: December 2019

AbstractThe development of drugs able to target BTK, PI3k‐delta and BCL2 has dramatically improved chronic lymphocytic leukaemia (CLL) therapies. However, drug resistance to these therapies has already been reported due to non‐recurrent changes in oncogenic pathways and genes expression signatures. In this study, we investigated the cooperative role of the BCL2 inhibitor venetoclax and the BRD4 inhibitor JQ1. In particular, we found that JQ1 shows additional activity with venetoclax, in CLL cell lines and in ex vivo isolated primary CD19+ lymphocytes, arguing in favour of combination strategies. Lastly, JQ1 is also effective in venetoclax‐resistant CLL cell lines. Together, our findings indicated that the BET inhibitor JQ1 could be a promising therapy in CLL, both as first‐line therapy in combination with venetoclax and as second‐line therapy, after the emergence of venetoclax‐resistant clones.
Proteomic and metabolomic profiling underlines the stage‐ and time‐dependent effects of high temperature on grape berry metabolism
Authors: Lecourieux David , Kappel Christian , Claverol Stéphane , Pieri Philippe , Feil Regina , Lunn John E. , Bonneu Marc , Wang Lijun , Gomès Eric , Delrot Serge , Lecourieux Fatma 
Published: December 2019

AbstractClimate change scenarios predict an increase in mean air temperatures and in the frequency, intensity, and length of extreme temperature events in many wine‐growing regions worldwide. Because elevated temperature has detrimental effects on berry growth and composition, it threatens the economic and environmental sustainability of wine production. Using Cabernet Sauvignon fruit‐bearing cuttings, we investigated the effects of high temperature (HT) on grapevine berries through a label‐free shotgun proteomic analysis coupled to a complementary metabolomic study. Among the 2,279 proteins identified, 592 differentially abundant proteins were found in berries exposed to HT. The gene ontology categories “stress,” “protein,” “secondary metabolism,” and “cell wall” were predominantly altered under HT. High temperatures strongly impaired carbohydrate and energy metabolism, and the effects depended on the stage of development and duration of treatment. Transcript amounts correlated poorly with protein expression levels in HT berries, highlighting the value of proteomic studies in the context of heat stress. Furthermore, this work reveals that HT alters key proteins driving berry development and ripening. Finally, we provide a list of differentially abundant proteins that can be considered as potential markers for developing or selecting grape varieties that are better adapted to warmer climates or extreme heat waves.
Activation of nicotinic acetylcholine receptors induces potentiation and synchronization within in vitro hippocampal networks
Authors: Djemil Sarra , Chen Xin , Zhang Ziyue , Lee Jisoo , Rauf Mikael , Pak Daniel T. S. , Dzakpasu Rhonda 
Published: December 2019

AbstractNicotinic acetylcholine receptors (nAChRs) are known to play a role in cognitive functions of the hippocampus, such as memory consolidation. Given that they conduct Ca2+ and are capable of regulating the release of glutamate and γ‐aminobutyric acid (GABA) within the hippocampus, thereby shifting the excitatory‐inhibitory ratio, we hypothesized that the activation of nAChRs will result in the potentiation of hippocampal networks and alter synchronization. We used nicotine as a tool to investigate the impact of activation of nAChRs on neuronal network dynamics in primary embryonic rat hippocampal cultures prepared from timed‐pregnant Sprague‐Dawley rats. We perturbed cultured hippocampal networks with increasing concentrations of bath‐applied nicotine and performed network extracellular recordings of action potentials using a microelectrode array. We found that nicotine modulated network dynamics in a concentration‐dependent manner; it enhanced firing of action potentials as well as facilitated bursting activity. In addition, we used pharmacological agents to determine the contributions of discrete nAChR subtypes to the observed network dynamics. We found that β4‐containing nAChRs are necessary for the observed increases in spiking, bursting, and synchrony, while the activation of α7 nAChRs augments nicotine‐mediated network potentiation but is not necessary for its manifestation. We also observed that antagonists of N‐methyl‐D‐aspartate receptors (NMDARs) and group I metabotropic glutamate receptors (mGluRs) partially blocked the effects of nicotine. Furthermore, nicotine exposure promoted autophosphorylation of Ca2+/calmodulin‐dependent kinase II (CaMKII) and serine 831 phosphorylation of the α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazolepropionic acid receptor (AMPAR) subunit GluA1. These results suggest that nicotinic receptors induce potentiation and synchronization of hippocampal networks and glutamatergic synaptic transmission. Findings from this work highlight the impact of cholinergic signaling in generating network‐wide potentiation in the form of enhanced spiking and bursting dynamics that coincide with molecular correlates of memory such as increased phosphorylation of CaMKII and GluA1.Open science badges

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The impact of surface alteration on epithelial tissue attachment after the mechanical cleaning of titanium or zirconia surface
Authors: Hu Jiangqi , Atsuta Ikiru , Ayukawa Yasunori , Zhou Xudiyang , Dwi Rakhmatia Yunia , Koyano Kiyoshi 
Published: December 2019

AbstractObjectiveMechanical plaque removal may alter the surface morphology of the gingival penetration part of the implant. We applied an air‐powered abrasive system (AP), titanium curette (TC), stainless curette (SC), ultrasound scaler (US), and titanium brush (TB) which are commonly used to remove plaque, to titanium or zirconia and the changes in surface morphology and the epithelial attach against substrata.Materials and Methods(a) The morphological changes of titanium and zirconia after mechanical cleaning were assessed by scanning electron microscopy and a roughness analyser. (b) Oral epithelial cells of rats were inoculated on the surface of the materials after mechanical cleaning, and the adherence of epithelial cells was observed. (c) The maxillary first molars were extracted from the rats and replaced by experimental titanium or zirconia implants. The length of the immunoreactive laminin‐332 band was observed at the implant‐peri‐implant epithelium interface.Results(a) The surface roughness increased in experimental groups except the AP group. (b) Among the experimental groups, the AP group showed the highest number of attached cells. (c) The length of the immunoreactive laminin‐332 band was longer in the control group than those in all five experimental groups. Among the experimental groups, the AP group showed the longest band.ConclusionAll mechanical cleaning methods increased the surface roughness of the materials except AP. AP did not cause distinct implant surface alterations. Surface alteration caused by mechanical cleaning may evoke inferior for epithelial attachment and reduce resistance against foreign infiltration.
The Role of Substance Use and Resiliency Factors on Suicidal Ideation among Middle School Students
Authors: Greene Naomi , Tomedi Laura , Reno Jessica , Green Dan 
Published: December 2019

ABSTRACTBACKGROUNDSuicidal ideation, an important risk factor for suicide, is strongly associated with substance use. Factors such as family cohesion, connection with friends, and social support can be protective against suicidal behaviors. The purpose of this study was to explore the association between suicidal ideation, substance use, and resiliency factors among middle school students.METHODSThe 2013 New Mexico Youth Risk and Resiliency Survey provided the data for this analysis. Suicidal ideation was defined as affirmative responses to questions about thoughts of killing oneself and/or making a suicide plan. We used logistic regression to explore the association between suicidal ideation, substance use, and resiliency factors.RESULTSOverall, 23% of students reported suicidal ideation. Among girls, having a caring friend was associated with lower odds of suicidal ideation only among those not using other drugs. Among boys, having a caring friend decreased the odds of suicidal ideation regardless of substance use.CONCLUSIONSSuicidal ideation is prevalent among middle school children. Substance abuse is associated with suicidal ideation; however, individual and community support can be protective. Interventions aimed at reducing suicidal behaviors among middle school students should account for the impact of substance use and help strengthen social support.
The importance of considering optimal government policy when social norms matter for the private provision of public goods
Authors: Meunier Guy , Schumacher Ingmar 
Published: December 2019

AbstractWe study optimal government policy in a reference model (Rege, 2004, Journal of Public Economic Theory, 6, 65–77) of public good provision and social approval in a dynamic setting. We show that even if complete adherence to the social norm maximizes social welfare it is by no means necessarily optimal to push society toward it. We stress the different roles of social externality and the public good problem. We discuss the problem with the standard crowding in and out argument and analyze the relationship with Pigouvian taxes. We discuss the role of the cost of public funds and show how it can create path dependency, the multiplicity of both optimal equilibria and optimal paths, and discuss the role of parameter instability.
PXR haplotype clusters will affect the pharmacokinetics of ciclosporin in Chinese renal transplant recipients
Authors: Li Danying , Zhu Huaijun , Luo Xuemei , Ge Weihong 
Published: December 2019

Abstract

Objective
PXR was reported to be the key nuclear receptor regulating the expression of metabolizing enzymes and transporters. The aim of this study was to evaluate the influence of PXR haplotype clusters on ciclosporin concentration in Chinese renal transplant recipients during the early stage after transplantation.

Methods
A total of 98 recipients receiving ciclosporin were genotyped by PCR-RFLP, and the ciclosporin concentration was determined by EMIT.

Key findings
The frequency of IVS2+55A&gt;G, IVS2+78A&gt;G, IVS6-17C&gt;T, 1792A&gt;G, 1944T&gt;C and 2654T&gt;C variant alleles was 0.343, 0.332, 0.378, 0.515, 0.520 and 0.393, which fitted Hardy–Weinberg equilibrium. Only the IVS6-17C&gt;T and 2654T&gt;C were significantly associated with the ciclosporin C2/D during the end of the first month. The mean ciclosporin C2/D level of the PXR*1B haplotype clusters was 1.3-fold and 1.2-fold higher compared with the *1A and *1C. No significant difference was observed in CsA C2/D between the PXR*1A and PXR*1C. We found no difference in C0/D among the six genotypes or the three haplotype clusters.

Conclusions
The PXR*1B in Chinese renal transplant patients was associated with ciclosporin concentration. Genetic polymorphisms and specific haplotype clusters in PXR could have significant contributory roles in affecting interethnic variations in drug disposition in the Chinese population.
Withanolides from the genus Physalis: a review on their phytochemical and pharmacological aspects
Authors: Huang Min , He Ji-Xiang , Hu Hui-Xin , Zhang Kan , Wang Xiao-Ning , Zhao Bao-Bing , Lou Hong-Xiang , Ren Dong-Mei , Shen Tao 
Published: December 2019

Abstract

Objectives
Withanolides are a group of modified C28 ergostane-type steroids with a C-22, C-26 δ-lactone side chain or a C-23, C-26 γ-lactone side chain. They enjoy a limited distribution in the plant kingdom and predominantly occur in several genera of Solanaceae. Of which, the genus Physalis is an important resource for this type of natural molecules. The present review aims to comprehensively illustrate the structural characteristics and classification of withanolides, and particularly focus on the progression on phytochemical and pharmacological aspects of withanolides from Physalis ranging from January 2015 to June 2019.

Key findings
Approximately 351 natural withanolides with novel and unique structures have so far been identified from genus Physalis, mainly isolated from the species of P. angulata and P. peruviana. Withanolides demonstrated diverse biological activity, such as anticancer, anti-inflammatory, antimicrobial, immunoregulatory, trypanocidal and leishmanicidal activity. Their observed pharmacological functions supported the uses of Physalis species in traditional or folk medicines.

Summary
Due to their unique structure skeleton and potent bioactivities, withanolides are regarded to be promising drug candidates, particularly for developing anticancer and anti-inflammatory agents. Further investigations for discovering novel withanolides of genus Physalis, exploiting their pharmacological values and evaluating their potency as therapeutic agents are significant work.
A new algorithm for optimization of rate‐adaptive pacing improves exercise tolerance in patients with HFpEF
Authors: Serova Maria , Andreev Denis , Giverts Ilya , Sazonova Yulia , Svet Aleksey , Kuklina Maria , Sedov Vsevolod , Syrkin Abram , Saner Hugo 
Published: December 2019

AbstractAimTo develop an algorithm for optimization of rate‐adaptive pacing settings in heart failure patients with preserved ejection fraction (HFpEF) and permanent cardiac pacing.MethodsThis is a prospective randomized controlled study. A total of 54 patients with HFpEF, permanent atrial fibrillation (AF), and VVIR pacing were randomized to an intervention group with optimization of rate‐adaptation parameters by using cardiopulmonary exercise testing (CPET) and pacemaker stress echocardiography (PASE), and to a control group with conventional programming. CPET, 6‐min walk test (6‐mwt), echocardiography (echo), Duke Activity Status Index (DASI), and Minnesota questionnaire (MLHFQ) were performed at baseline and after 3 months. PASE was used to exclude exercise‐induced ischemia and to determine safe upper sensor rate. Pacing parameters were corrected to achieve optimal heart rate increments of 3‐6 bpm for 1 mL/min/kg of VO2 (oxygen uptake).ResultsAfter 3 months, the intervention group demonstrated significant improvement of VO2 peak by 1.64 ± 1.6 mL/min/kg, anaerobic threshold by 1.33 ± 1.3 mL/min/kg, exercise time by 170 ± 98 s, 6‐mwt distance by 75 ± 63 m (P < .0001 for all), DASI by 5.23 points (P = .009), MLHFQ‐score (reduction by 9 points, P < .0001), and echo parameters (decrease in LA volume from 108 (84; 132) to 95 (85; 130) mL, P = .026; E/e’ from 11.7 ± 3.2 to 10.4 ± 2.9, P = .025; systolic pulmonary artery pressure (SPAP) from 44 ± 14 to 39 ± 12 mm Hg, P = .001) compared to the control group.ConclusionAn algorithm incorporating CPET and PASE for optimal programming of rate‐adaptation parameters is a valuable tool to improve exercise capacity in HFpEF patients with permanent AF and VVIR pacing who remain exercise intolerant after conventional programming.
Photodynamic Therapy for Cancer: What's Past is Prologue
Authors: Hamblin Michael R. 
Published: December 2019

AbstractThomas J Dougherty from Roswell Park Cancer Center played a major role in the progress of photodynamic therapy (PDT) from a laboratory science into a real‐world clinical therapy to treat patients with cancer. Nevertheless over the succeeding 45 years, it is fair to say that the overall progress of clinical PDT for cancer has been somewhat disappointing. The goal of this perspective article is to summarize some of the clinical trials run by various companies using photosensitizers with different structures that have been conducted for different types of cancer. While some have been successful, others have failed, and several are now ongoing. I will attempt to touch on some factors, which have influenced this checkered history and look forward to the future of clinical PDT for cancer.
Examination of jackass (Equus asinus) accessory sex glands by B‐mode ultrasound and of testicular artery blood flow by colour pulsed‐wave Doppler ultrasound: Correlations with semen production
Authors: Gacem Sabrina , Papas Marion , Catalan Jaime , Miró Jordi 
Published: December 2019

AbstractThe accessory sex glands play a major role in the production of seminal plasma, and testicular artery blood flow seems to strongly influence testicular function. However, very little ultrasound imaging of these organs has been undertaken in donkeys. The present work reports the results of such examinations in five jackasses along the year. The accessory glands were inspected by B‐mode ultrasound while the testicular artery blood flow was assessed by colour pulsed‐wave Doppler ultrasound. The testicular artery was examined at pampiniform plexus (PPT), supratesticular area (ST) and capsular artery (CA). Values were recorded for the total arterial blood flow (TABF), peak systolic velocity (PSV), end‐diastolic velocity (EDV), resistive index (RI), pulsatility index (PI) and time average maximum velocity (TAMV). Semen was obtained and assessed for sperm concentration, viability, abnormalities and motility using a CASA system. The bulbourethral glands, prostate and ductus deferens ampullae were relatively larger than in the stallion. Bulbourethral glands and ampullae sizes were inversely correlated with sperm motility. An reduction in blood flow between the level the PPP and the CA was observed, helping to reduce testis temperature and oxygen pressure. Blood flow at the CA showed the strongest correlation with semen production. PI and RI were positively correlated with the CASA motility variable STR (p = .02, p = .06) and sperm viability (p = .01), while sperm concentration (p = .05) correlated inversely with PSV, EDV, TAMV and TABF. EDV also correlated negatively with the CASA variables VSL, LIN, STR and VAP (p ≤ .05). PI and RI were also negatively correlated with testis length (p = .0093, p = −.0438).
The Lost Patriarchs Project: Recovering the Greek Fathers in the medieval Latin tradition
Authors: Bruce Scott G. 
Published: December 2019

AbstractThis article calls attention to an important, yet neglected, subset of medieval Latin sources: the dozens upon dozens of works of late antique and early Byzantine Christian Greek authors translated into Latin between the second and the thirteenth centuries. It also introduces a new initiative to study these sources: The Lost Patriarchs Project. The goal of this article is threefold. First, it presents a sample of the deep, virtually untouched reservoir of medieval Latin texts that have Greek origins, including patristics, hagiography, and apocrypha, and marshals evidence for their use among medieval readers. Second, it considers some of the reasons why this corpus of medieval Latin literature has not been subject to critical inquiry. Third, it announces plans for a new instrument of reference tentatively entitled The Lost Patriarchs: A Survey of the Greek Fathers in the Medieval Latin Tradition. A reference tool of this kind would gather all that is known about these texts in current scholarship, allowing future researchers to begin the work of creating critical editions of them and incorporating them into our understanding of medieval thought.