bluuebunny/crossref_metadata_2025_split huggingface dataset:
Predictive validation of qualitative fibrosis staging in patients with chronic hepatitis B on antiviral therapy
Authors: Lee Hye Won , Na Kiyong , Kim Seung Up , Kim Beom Kyung , Park Jun Yong , Nahm Ji Hae , Lee Jung Il , Kim Do Young , Ahn Sang Hoon , Han Kwang-Hyub , Park Young Nyun 
Published: October 2019

AbstractThe fibrosis in chronic hepatitis shows dynamic changes during antiviral therapy (AVT). We investigated whether P-I-R (progressive vs. indeterminate vs. regressive) staging is predictive of hepatocellular carcinoma (HCC) recurrence in patients with chronic hepatitis B (CHB) taking AVT who underwent resection. Patients with CHB-related HCC who underwent curative resection between 2004 and 2017 and had received ≥2 years AVT at the time of resection were eligible. Two pathologists performed P-I-R staging. In total, 104 patients with CHB-related HCC were enrolled. The mean age of the study population was 56.3 years. The mean duration of AVT at the time of resection was 62.6 months. During the follow-up period (mean, 45.5 months), 20 (19.2%) and 14 (13.5%) patients developed early and late recurrence of HCC, respectively. The cumulative incidence of late recurrence was significantly lower in patients with regressive patterns than in those with indeterminate and progressive patterns according to P-I-R staging (P = 0.015, log-rank test), although the cumulative incidence of overall recurrence according to P-I-R staging was similar. Hepatitis B virus DNA levels (hazard ratio [HR] = 3.200, P = 0.020) and the regressive P-I-R staging pattern (HR = 0.127, P = 0.047) independently predicted the risk of late recurrence. One-time assessment of the P-I-R staging at the time of curative resection in patients with CHB-related HCC receiving AVT independently predicted late HCC recurrence. Therefore, qualitative fibrosis assessment by P-I-R staging might be useful in predicting the outcomes of patients with CHB undergoing AVT.
Uremic serum residue decreases SN-38 sensitivity through suppression of organic anion transporter polypeptide 2B1 in LS-180 colon cancer cells
Authors: Ozawa Shoichi , Tsujimoto Masayuki , Uchiyama Hitoshi , Ito Natsuko , Morishita Satoe , Yamamoto Mizuki , Irie Ryosuke , Sakashita Tohko , Tachiki Hidehisa , Furukubo Taku , Izumi Satoshi , Yamakawa Tomoyuki , Minegaki Tetsuya , Nishiguchi Kohshi 
Published: October 2019

AbstractPharmacokinetics of SN-38 in patients with end-stage kidney disease (ESKD) is partially varied because of fluctuations in transporters expression and/or function by high protein bound-uremic toxins concentration. The fluctuations may induce variations in anticancer drugs sensitivity to cancer cells. We aimed to clarify the variations in sensitivity of SN-38 to cancer patients with ESKD and investigate this mechanism, by human colon cancer cells exposed to uremic serum residue. LS180 cells were exposed to normal or uremic serum residue (LS/NSR or LS/USR cells) for a month. IC50 values of SN-38 in LS/NSR or LS/USR cells were calculated from viability of each cells treated SN-38. mRNA expression and intracellular SN-38 accumulation was evaluated by RT-PCR and HPLC-fluorescence methods, respectively. The IC50 value in LS/USR cells was higher than that in LS/NSR cells. Organic anion transporter polypeptide (OATP) 2B1 mRNA expression was lower in LS/USR cells than in LS/NSR cells, and SN-38 accumulation in LS/USR cells was lower than that in LS/NSR cells. Only co-treatment baicalin, which is OATP2B1 inhibitor, almost negated the difference in SN-38 accumulation between LS/NSR and LS/USR. Anticancer effects of substrates of OATP2B1, such as SN-38, were reduced in ESKD patients at the same plasma substrate concentration.
Repeated buffered acidic saline infusion in the human masseter muscle as a putative experimental pain model
Authors: Louca Jounger Sofia , Eriksson Niklas , Lindskog Helena , Oscarsson Anna , Simonsson Vivian , Ernberg Malin , Christidis Nikolaos 
Published: October 2019

AbstractThis study investigated if repeated buffered acidic saline infusions into the masseter muscles induced muscle pain and mechanical sensitization. Fourteen healthy men participated in this double-blind, randomized, and placebo-controlled study. Two repeated infusions (day 1 and 3) were given in the masseter muscles with either a buffered acidic saline solution (pH 5.2) or an isotonic saline solution (pH 6) as control. After 10 days of wash-out, the experiment was repeated with the other substance. Pressure pain thresholds (PPT), pain intensity, maximum unassisted mouth opening (MUO), and pain drawings were assessed before, directly following, and after each infusion at 5, 15, and 30 min and on day 4 and 7. Fatigue and pain intensity were assessed after a one-minute chewing test 30 min after infusions and day 4 and 7. Acidic saline induced higher pain intensity than control day 3 up to 5 min after infusions, but did not affect PPT. The chewing test did not evoke higher fatigue during chewing or MUO or after acidic saline infusion compared to control. Repeated acidic saline infusions in the masseter muscles induced a short-lasting muscle pain without mechanical hyperalgesia or functional pain. Hence, this model might not be superior to already existing experimental muscle pain models.
Targeted deletion of NFAT-Interacting-Protein-(NIP) 45 resolves experimental asthma by inhibiting Innate Lymphoid Cells group 2 (ILC2)
Authors: Koch Sonja , Knipfer Lisa , Kölle Julia , Mirzakhani Hooman , Graser Anna , Zimmermann Theodor , Kiefer Alexander , Melichar Volker O. , Rascher Wolfgang , Papadopoulos Nikolaos G. , Rieker Ralf J. , Raby Benjamin A. , Weiss Scott T. , Wirtz Stefan , Finotto Susetta 
Published: October 2019

AbstractHere we investigated the role of NFAT-interacting protein (NIP)-45, an Interleukin (IL)-4 inducing Transcription Factor, and its impact on the differentiation of Group 2 Innate -Lymphoid -Cells (ILC2s) in the pathogenesis of asthma. NIP45, a transcription factor regulating NFATc1 activity, mRNA was found to be induced in the Peripheral Blood mononuclear cells (PMBCs) of asthmatic pre-school children with allergies and in the peripheral blood CD4+ T cells from adult asthmatic patients. In PBMCs of asthmatic and control children, NIP45 mRNA directly correlated with NFATc1 but not with T-bet. Targeted deletion of NIP45 in mice resulted in a protective phenotype in experimental asthma with reduced airway mucus production, airway hyperresponsiveness and eosinophils. This phenotype was reversed by intranasal delivery of recombinant r-IL-33. Consistently, ILC2s and not GATA3+ CD4+ T-cells were decreased in the lungs of asthmatic NIP45−/− mice. Reduced cell number spleen ILC2s could be differentiated from NIP45−/− as compared to wild-type mice after in vivo injection of a microcircle-DNA vector expressing IL-25 and decreased cytokines and ILC2 markers in ILC2 differentiated from the bone marrow of NIP45−/− mice. NIP45 thus emerges as a new therapeutic target for the resolution of the airway pathology, down-regulation of ILC2s and mucus production in asthma.
Monotherapy versus combination therapy for multidrug-resistant Gram-negative infections: Systematic Review and Meta-Analysis
Authors: Schmid Adrian , Wolfensberger Aline , Nemeth Johannes , Schreiber Peter W. , Sax Hugo , Kuster Stefan P. 
Published: October 2019

AbstractInfections caused by carbapenemase-producing, multidrug-resistant (MDR), or extensively drug-resistant (XDR) Gram-negative bacteria constitute a major therapeutic challenge. Whether combination antibiotic therapy is superior to monotherapy remains unknown. In this systematic review and meta-analysis OVID MEDLINE, EMBASE, PubMed, The Cochrane Library, and Scopus databases were searched for randomized controlled trials (RCTs) and observational studies published by December 2016 comparing mono- with combination antibiotic therapy for infections with carbapenemase-producing, MDR, or XDR Gram-negative bacteria. Mortality and clinical cure rates served as primary and secondary outcome measures, respectively. Of 8847 initially identified studies, 53 studies – covering pneumonia (n = 10 studies), blood stream (n = 15), osteoarticular (n = 1), and mixed infections (n = 27) - were included. 41% (n = 1848) of patients underwent monotherapy, and 59% (n = 2666) combination therapy. In case series/cohort studies (n = 45) mortality was lower with combination- vs. monotherapy (RR 0.83, CI 0.73–0.93, p = 0.002, I2 = 24%). Subgroup analysis revealed lower mortality with combination therapy with at least two in-vitro active antibiotics, in blood stream infections, and carbapenemase-producing Enterobacteriaceae. No mortality difference was seen in case-control studies (n = 6) and RCTs (n = 2). Cure rates did not differ regardless of study type. The two included RCTs had a high and unknown risk of bias, respectively. 16.7% (1/6) of case-control studies and 37.8% (17/45) of cases series/cohort studies were of good quality, whereas quality was poor in the remaining studies. In conclusion, combination antimicrobial therapy of multidrug-resistant Gram-negative bacteria appears to be superior to monotherapy with regard to mortality.
Diverging roles of the anterior insula in trauma-exposed individuals vulnerable or resilient to posttraumatic stress disorder
Authors: Jeong Hyeonseok , Chung Yong-An , Ma Jiyoung , Kim Jungyoon , Hong Gahae , Oh Jin Kyoung , Kim Myeongju , Ha Eunji , Hong Haejin , Yoon Sujung , Lyoo In Kyoon 
Published: October 2019

AbstractDistinct brain alterations in response to traumatic events may render trauma-exposed individuals either resilient or vulnerable to posttraumatic stress disorder (PTSD). This study compared regional cerebral metabolic rate of glucose (rCMRglu) among trauma-exposed individuals with current PTSD (PTSD group, n = 61), those without current PTSD (Resilience/Recovery group, n = 26), and trauma-unexposed controls (Control group, n = 54). All participants underwent brain [18F]-fluorodeoxyglucose positron emission tomography (FDG-PET) scans. Voxel-wise group differences in rCMRglu among the three groups were evaluated. Associations between rCMRglu and both PTSD severity and resilience were examined. The rCMRglu in the right anterior insula and adjacent prefrontal and striatal areas was lower in the PTSD group, while higher in the Resilience/Recovery group, compared to the Control group. In addition, the lower glucose metabolism of these areas was associated with higher severity and less improvement in PTSD symptoms in the PTSD group, while the higher levels of rCMRglu were correlated with stronger resilience in the Resilience/Recovery group. This study suggests distinct roles of the anterior insula in response to trauma between the PTSD and Resilience/Recovery groups. Heightened rCMRglu in the anterior insular regions may reflect an underlying mechanism of resilience against traumatic stress, while reduced rCMRglu may indicate vulnerability to PTSD.
Radiation-induced malignancies after intensity-modulated versus conventional mediastinal radiotherapy in a small animal model
Authors: Gomarteli Kaga , Fleckenstein Jens , Kirschner Stefanie , Bobu Vladimir , Brockmann Marc A. , Henzler Thomas , Meyer Mathias , Riffel Philipp , Schönberg Stefan O. , Veldwijk Marlon R. , Kränzlin Bettina , Hoerner Christian , Glatting Gerhard , Wenz Frederik , Herskind Carsten , Giordano Frank A. 
Published: October 2019

AbstractA long-standing hypothesis in radiotherapy is that intensity-modulated radiotherapy (IMRT) increases the risk of second cancer due to low-dose exposure of large volumes of normal tissue. Therefore, young patients are still treated with conventional techniques rather than with modern IMRT. We challenged this hypothesis in first-of-its-kind experiments using an animal model. Cancer-prone Tp53+/C273X knockout rats received mediastinal irradiation with 3 × 5 or 3 × 8 Gy using volumetric-modulated arc therapy (VMAT, an advanced IMRT) or conventional anterior-posterior/posterior-anterior (AP/PA) beams using non-irradiated rats as controls (n = 15/group, ntotal = 90). Tumors were assigned to volumes receiving 90–107%, 50–90%, 5–50%, and <5% of the target dose and characterized by histology and loss-of-heterozygosity (LOH). Irradiated rats predominantly developed lymphomas and sarcomas in areas receiving 50–107% (n = 26) rather than 5–50% (n = 7) of the target dose. Latency was significantly shortened only after 3 × 8 Gy vs. controls (p < 0.0001). The frequency (14/28 vs. 19/29; p = 0.29) and latency (218 vs. 189 days; p = 0.17) of radiation-associated tumors were similar after VMAT vs. AP/PA. LOH was strongly associated with sarcoma but not with treatment. The results do not support the hypothesis that IMRT increases the risk of second cancer. Thus the current practice of withholding dose-sparing IMRT from young patients may need to be re-evaluated.
Maladaptive alterations of resting state cortical network in Tinnitus: A directed functional connectivity analysis of a larger MEG data set
Authors: Paraskevopoulos Evangelos , Dobel Christian , Wollbrink Andreas , Salvari Vasiliki , Bamidis Panagiotis D. , Pantev Christo 
Published: October 2019

AbstractThe present study used resting state MEG whole-head recordings to identify how chronic tonal tinnitus relates to altered functional connectivity of brain’s intrinsic cortical networks. Resting state MEG activity of 40 chronic tinnitus patients and 40 matched human controls was compared identifying significant alterations in intrinsic networks of the tinnitus population. Directed functional connectivity of the resting brain, at a whole cortex level, was estimated by means of a statistical comparison of the estimated phase Transfer Entropy (pTE) between the time-series of cortical activations, as reconstructed by LORETA. As pTE identifies the direction of the information flow, a detailed analysis of the connectivity differences between tinnitus patients and controls was possible. Results indicate that the group of tinnitus patients show increased connectivity from right dorsal prefrontal to right medial temporal areas. Our results go beyond previous findings by indicating that the role of the left para-hippocampal area is dictated by a modulation from dmPFC; a region that is part of the dorsal attention network (DAN), as well as implicated in the regulation of emotional processing. Additionally, this whole cortex analysis showed a crucial role of the left inferior parietal cortex, which modulated the activity of the right superior temporal gyrus, providing new hypotheses for the role of this area within the context of current tinnitus models. Overall, these maladaptive alterations of the structure of intrinsic cortical networks show a decrease in efficiency and small worldness of the resting state network of tinnitus patients, which is correlated to tinnitus distress.
Broad North Atlantic distribution of a meiobenthic annelid – against all odds
Authors: Worsaae Katrine , Kerbl Alexandra , Vang Áki , Gonzalez Brett C. 
Published: October 2019

AbstractDNA barcoding and population genetic studies have revealed an unforeseen hidden diversity of cryptic species among microscopic marine benthos, otherwise exhibiting highly similar and simple morphologies. This has led to a paradigm shift, rejecting cosmopolitism of marine meiofauna until genetically proven and challenging the “Everything is Everywhere, but the environment selects” hypothesis that claims ubiquitous distribution of microscopic organisms. With phylogenetic and species delimitation analyses of worldwide genetic samples of the meiofaunal family Dinophilidae (Annelida) we here resolve three genera within the family and showcase an exceptionally broad, boreal, North Atlantic distribution of a single microscopic marine species with no obvious means of dispersal besides vicariance. With its endobenthic lifestyle, small size, limited migratory powers and lack of pelagic larvae, the broad distribution ofDinophilus vorticoidesseems to constitute a “meiofaunal paradox”. This species feasts in the biofilm among sand grains, but also on macroalgae and ice within which it can likely survive long-distance rafting dispersal due to its varying lifecycle stages; eggs encapsulated in cocoons and dormant encystment stages. Though often neglected and possibly underestimated among marine microscopic species, dormancy may be a highly significant factor for explaining wide distribution patterns and a key to solving this meiofaunal paradox.
Machine Friendly Machine Learning: Interpretation of Computed Tomography Without Image Reconstruction
Authors: Lee Hyunkwang , Huang Chao , Yune Sehyo , Tajmir Shahein H. , Kim Myeongchan , Do Synho 
Published: October 2019

AbstractRecent advancements in deep learning for automated image processing and classification have accelerated many new applications for medical image analysis. However, most deep learning algorithms have been developed using reconstructed, human-interpretable medical images. While image reconstruction from raw sensor data is required for the creation of medical images, the reconstruction process only uses a partial representation of all the data acquired. Here, we report the development of a system to directly process raw computed tomography (CT) data in sinogram-space, bypassing the intermediary step of image reconstruction. Two classification tasks were evaluated for their feasibility of sinogram-space machine learning: body region identification and intracranial hemorrhage (ICH) detection. Our proposed SinoNet, a convolutional neural network optimized for interpreting sinograms, performed favorably compared to conventional reconstructed image-space-based systems for both tasks, regardless of scanning geometries in terms of projections or detectors. Further, SinoNet performed significantly better when using sparsely sampled sinograms than conventional networks operating in image-space. As a result, sinogram-space algorithms could be used in field settings for triage (presence of ICH), especially where low radiation dose is desired. These findings also demonstrate another strength of deep learning where it can analyze and interpret sinograms that are virtually impossible for human experts.
In vitro potentiation of doxorubicin by unseeded controlled non-inertial ultrasound cavitation
Authors: Fant Cécile , Lafond Maxime , Rogez Bernadette , Castellanos Ivan Suarez , Ngo Jacqueline , Mestas Jean-Louis , Padilla Frédéric , Lafon Cyril 
Published: October 2019

AbstractUltrasound-generated non-inertial cavitation has the ability to potentiate the therapeutic effects of cytotoxic drugs. We report a novel strategy to induce and regulate unseeded (without nucleation agents) non-inertial cavitation, where cavitation is initiated, monitored and regulated using a confocal ultrasound setup controlled by an instrumentation platform and a PC programmed feedback control loop. We demonstrate, using 4T1 murine mammary carcinoma as model cell line, that unseeded non-inertial cavitation potentiates the cytotoxicity of doxorubicin, one of the most potent drugs used in the treatment of solid tumors including breast cancer. Combined treatment with doxorubicin and unseeded non-inertial cavitation significantly reduced cell viability and proliferation at 72 h. A mechanistic study of the potential mechanisms of action of the combined treatment identified the presence of cavitation as required to enhance doxorubicin efficacy, but ruled out the influence of changes in doxorubicin uptake, temperature increase, hydroxyl radical production and nuclear membrane modifications on the treatment outcome. The developed strategy for the reproducible generation and maintenance of unseeded cavitation makes it an attractive method as potential preclinical and clinical treatment modality to locally potentiate doxorubicin.
Transcriptome analysis reveals microvascular endothelial cell-dependent pericyte differentiation
Authors: Brandt Maarten M. , van Dijk Christian G. M. , Maringanti Ranganath , Chrifi Ihsan , Kramann Rafael , Verhaar Marianne C. , Duncker Dirk J. , Mokry Michal , Cheng Caroline 
Published: October 2019

AbstractMicrovascular homeostasis is strictly regulated, requiring close interaction between endothelial cells and pericytes. Here, we aimed to improve our understanding of how microvascular crosstalk affects pericytes. Human-derived pericytes, cultured in absence, or presence of human endothelial cells, were studied by RNA sequencing. Compared with mono-cultured pericytes, a total of 6704 genes were differentially expressed in co-cultured pericytes. Direct endothelial contact induced transcriptome profiles associated with pericyte maturation, suppression of extracellular matrix production, proliferation, and morphological adaptation. In vitro studies confirmed enhanced pericyte proliferation mediated by endothelial-derived PDGFB and pericyte-derived HB-EGF and FGF2. Endothelial-induced PLXNA2 and ACTR3 upregulation also triggered pericyte morphological adaptation. Pathway analysis predicted a key role for TGFβ signaling in endothelial-induced pericyte differentiation, whereas the effect of signaling via gap- and adherens junctions was limited. We demonstrate that endothelial cells have a major impact on the transcriptional profile of pericytes, regulating endothelial-induced maturation, proliferation, and suppression of ECM production.
Unfolding political attitudes through the face: facial expressions when reading emotion language of left- and right-wing political leaders
Authors: Fino Edita , Menegatti Michela , Avenanti Alessio , Rubini Monica 
Published: October 2019

AbstractSpontaneous emotionally congruent facial responses (ECFR) to others’ emotional expressions can occur by simply observing others’ faces (i.e., smiling) or by reading emotion related words (i.e., to smile). The goal of the present study was to examine whether language describing political leaders’ emotions affects voters by inducing emotionally congruent facial reactions as a function of readers’ and politicians’ shared political orientation. Participants read sentences describing politicians’ emotional expressions, while their facial muscle activation was measured by means of electromyography (EMG). Results showed that reading sentences describing left and right-wing politicians “smiling” or “frowning” elicits ECFR for ingroup but not outgroup members. Remarkably, ECFR were sensitive to attitudes toward individual leaders beyond the ingroup vs. outgroup political divide. Through integrating behavioral and physiological methods we were able to consistently tap on a ‘favored political leader effect’ thus capturing political attitudes towards an individual politician at a given moment of time, at multiple levels (explicit responses and automatic ECFR) and across political party membership lines. Our findings highlight the role of verbal behavior of politicians in affecting voters’ facial expressions with important implications for social judgment and behavioral outcomes.