bluuebunny/crossref_metadata_2025_split huggingface dataset:
Treatment of non-erosive reflux disease and dynamics of the esophageal microbiome: a prospective multicenter study
Authors: Park Chan Hyuk , Seo Seung In , Kim Joon Sung , Kang Sun Hyung , Kim Beom Jin , Choi Yoon Jin , Byun Hyo Joo , Yoon Jung-Ho , Lee Sang Kil 
Published: September 2020

AbstractNon-erosive reflux disease (NERD) pathogenesis has not been thoroughly evaluated. Here, we assessed the response of patients with NERD to proton pump inhibitor (PPI) therapy; changes in the microbiome and biologic marker expression in the esophageal mucosa were also evaluated. Patients with NERD (n = 55) received esomeprazole (20 mg) for eight weeks. The treatment response was evaluated at baseline, week four, and week eight. Esophageal mucosal markers and oropharyngeal and esophageal microbiomes were analyzed in patients who underwent upper gastrointestinal endoscopy at screening (n = 18). Complete and partial response rates at week eight were 60.0% and 32.7% for heartburn, and 61.8% and 29.1% for regurgitation, respectively. The expressions of several inflammatory cytokines, including IL-6, IL-8, and NF-κB, were decreased at week eight. Streptococcus, Haemophilus, Prevotella, Veillonella, Neisseria, and Granulicatella were prevalent regardless of the time-point (baseline vs. week eight) and organ (oropharynx vs. esophagus). The overall composition of oropharyngeal and esophageal microbiomes showed significant difference (P = 0.004), which disappeared after PPI therapy. In conclusion, half-dose PPI therapy for eight weeks could effectively control NERD symptoms. The expression of several inflammatory cytokines was reduced in the esophagus, and oropharyngeal and esophageal microbiomes in patients with NERD showed significant difference. However, the microbial compositions in the oropharynx and esophagus were not affected by PPI therapy in this study. Impact of PPI on the microbiome in patients with NERD should be more investigated in future studies.
A membrane transporter determines the spectrum of activity of a potent platinum–acridine hybrid anticancer agent
Authors: Yao Xiyuan , Watkins Noah H. , Brown-Harding Heather , Bierbach Ulrich 
Published: September 2020

AbstractCytotoxic drugs that are mechanistically distinct from current chemotherapies are attractive components of personalized combination regimens for combatting aggressive forms of cancer. To gain insight into the cellular mechanism of a potent platinum–acridine anticancer agent (compound 1), a correlation analysis of NCI-60 compound screening results and gene expression profiles was performed. A plasma membrane transporter, the solute carrier (SLC) human multidrug and toxin extrusion protein 1 (hMATE1, SLC47A1), emerged as the dominant predictor of cancer cell chemosensitivity to the hybrid agent (Pearson correlation analysis, p < 10–5) across a wide range of tissues of origin. The crucial role of hMATE1 was validated in lung adenocarcinoma cells (A549), which expresses high levels of the membrane transporter, using transporter inhibition assays and transient knockdown of the SLC47A1 gene, in conjunction with quantification of intracellular accumulation of compound 1 and cell viability screening. Preliminary data also show that HCT-116 colon cancer cells, in which hMATE1 is epigenetically repressed, can be sensitized to compound 1 by priming the cells with the drugs EPZ-6438 (tazemetostat) and EED226. Collectively, these results suggest that hMATE1 may have applications as a pan-cancer molecular marker to identify and target tumors that are likely to respond to platinum–acridines.
Extracellular vesicles produced by immunomodulatory cells harboring OX40 ligand and 4-1BB ligand enhance antitumor immunity
Authors: Semionatto Isadora Ferraz , Palameta Soledad , Toscaro Jéssica Marcelino , Manrique-Rincón Andrea Johanna , Ruas Luciana Pereira , Paes Leme Adriana Franco , Bajgelman Marcio Chaim 
Published: September 2020

AbstractGenetically modified tumor cells harboring immunomodulators may be used as therapeutic vaccines to stimulate antitumor immunity. The therapeutic benefit of these tumor vaccines is extensively investigated and mechanisms by which they boost antitumor response may be further explored. Tumor cells are large secretors of extracellular vesicles (EVs). These EVs are able to vehiculate RNA and proteins to target cells, and engineered EVs also vehiculate recombinant proteins. In this study, we explore immunomodulatory properties of EVs derived from antitumor vaccines expressing the TNFSF ligands 4-1BBL and OX40L, modulating immune response mediated by immune cells and eliminating tumors. Our results suggest that the EVs secreted by genetically modified tumor cells harboring TNFSF ligands can induce T cell proliferation, inhibit the transcription factor FoxP3, associated with the maintenance of Treg phenotype, and enhance antitumor activity mediated by immune cells. The immunomodulatory extracellular vesicles have potential to be further engineered for developing new approaches for cancer therapy.
Predominant synthesis of giant myofibrillar proteins in striated muscles of the long-tailed ground squirrel Urocitellus undulatus during interbout arousal
Authors: Popova Svetlana , Ulanova Anna , Gritsyna Yulia , Salmov Nikolay , Rogachevsky Vadim , Mikhailova Gulnara , Bobylev Alexander , Bobyleva Liya , Yutskevich Yana , Morenkov Oleg , Zakharova Nadezda , Vikhlyantsev Ivan 
Published: September 2020

AbstractMolecular mechanisms underlying muscle-mass retention during hibernation have been extensively discussed in recent years. This work tested the assumption that protein synthesis hyperactivation during interbout arousal of the long-tailed ground squirrel Urocitellus undulatus should be accompanied by increased calpain-1 activity in striated muscles. Calpain-1 is known to be autolysed and activated in parallel. Western blotting detected increased amounts of autolysed calpain-1 fragments in the heart (1.54-fold, p < 0.05) and m. longissimus dorsi (1.8-fold, p < 0.01) of ground squirrels during interbout arousal. The total protein synthesis rate determined by SUnSET declined 3.67-fold in the heart (p < 0.01) and 2.96-fold in m. longissimus dorsi (p < 0.01) during interbout arousal. The synthesis rates of calpain-1 substrates nebulin and titin in muscles did not differ during interbout arousal from those in active summer animals. A recovery of the volume of m. longissimus dorsi muscle fibres, a trend towards a heart-muscle mass increase and a restoration of the normal titin content (reduced in the muscles during hibernation) were observed. The results indicate that hyperactivation of calpain-1 in striated muscles of long-tailed ground squirrels during interbout arousal is accompanied by predominant synthesis of giant sarcomeric cytoskeleton proteins. These changes may contribute to muscle mass retention during hibernation.
Incidence of maternal near-miss in Kenya in 2018: findings from a nationally representative cross-sectional study in 54 referral hospitals
Authors: Owolabi Onikepe , Riley Taylor , Juma Kenneth , Mutua Michael , Pleasure Zoe H. , Amo-Adjei Joshua , Bangha Martin 
Published: September 2020

AbstractAlthough the Kenyan government has made efforts to invest in maternal health over the past 15 years, there is no evidence of decline in maternal mortality. To provide necessary evidence to inform maternal health care provision, we conducted a nationally representative study to describe the incidence and causes of maternal near-miss (MNM), and the quality of obstetric care in referral hospitals in Kenya. We collected data from 54 referral hospitals in 27 counties. Individuals admitted with potentially life-threatening conditions (using World Health Organization criteria) in pregnancy, childbirth or puerperium over a three month study period were eligible for inclusion in our study. All cases of severe maternal outcome (SMO, MNM cases and deaths) were prospectively identified, and after consent, included in the study. The national annual incidence of MNM was 7.2 per 1,000 live births and the intra-hospital maternal mortality ratio was 36.2 per 100,000 live births. The major causes of SMOs were postpartum haemorrhage and severe pre-eclampsia/eclampsia. However, only 77% of women with severe preeclampsia/eclampsia received magnesium sulphate and 67% with antepartum haemorrhage who needed blood received it. To reduce the burden of SMOs in Kenya, there is need for timely management of complications and improved access to essential emergency obstetric care interventions.
Changes in grassland management and linear infrastructures associated to the decline of an endangered bird population
Authors: Marques Ana Teresa , Moreira Francisco , Alcazar Rita , Delgado Ana , Godinho Carlos , Sampaio Hugo , Rocha Pedro , Sequeira Nuno , Palmeirim Jorge M. , Silva João Paulo 
Published: September 2020

AbstractEuropean grassland birds are experiencing major population declines, mainly due to changes in farmland management. We analyzed the role of habitat availability, grazing management and linear infrastructures (roads and power lines) in explaining spatial and temporal variation in the population density of little bustards (Tetrax tetrax) in Portugal, during a decade in which the species population size halved. We used data from 51 areas (totaling ca. 1,50,000 ha) that were sampled in two different periods (2003–2006 and 2016). In 2003–2006, when the species occurred at high densities, habitat availability was the only factor affecting spatial variation in bustard density. In the 2016 survey, variation in density was explained by habitat availability and livestock management, with reduced bird numbers in areas with higher proportions of cattle. Population declines across the study period were steeper in areas that initially held higher densities of bustards and in areas with a higher proportion of cattle in the total stocking rate. Areas with higher densities of power lines also registered greater density declines, probably due to avoidance behavior and to increased mortality. Overall, our results show little bustards are currently lacking high quality grassland habitat, whose persistence depends on extensive grazing regimes and low linear infrastructure densities.
Changes in the concentrations of trimethylamine N-oxide (TMAO) and its precursors in patients with amyotrophic lateral sclerosis
Authors: Chen Lu , Chen Yong , Zhao Mingming , Zheng Lemin , Fan Dongsheng 
Published: September 2020

AbstractTo compare the plasma concentrations of trimethylamine N-oxide (TMAO) and its precursors in amyotrophic lateral sclerosis (ALS) patients, their spouses and healthy controls and to find associations between gut microbiota metabolites and ALS. ALS patients were recruited at Peking University Third Hospital from January 2015 to December 2018. Information was collected from their spouses at the same time. Age and gender matched healthy controls were recruited from individuals who visited the physical examination center for health checkups. Blood samples were collected after at least 4 h of fasting. Concentrations of the metabolites were quantified using stable isotope dilution liquid chromatography–tandem mass spectrometry. Group differences were analyzed using parametric and nonparametric tests, as appropriate. In this study, 160 patients with ALS were recruited. In these patients, 63 were compared with their spouses, 148 were compared with age and gender matched controls, and 60 were compared with both their spouses and heathy controls in the same time. The carnitine concentration was significantly higher in patients than in their spouses, while there were no significant differences in the concentrations of other metabolites. The carnitine and betaine concentrations were higher, while the choline, TMAO and butyrobetaine concentrations were lower in ALS than in healthy controls. The concentrations of the metabolites in the spouses were more similar to the ALS patients rather than to the healthy controls. In the ALS group, the plasma concentrations of carnitine, betaine, choline and TMAO were inversely related to the severity of upper motor neuron impairment. The TMAO metabolic pathway of the gut microbiota is disturbed in both ALS patients and their spouses, which might suggest that the changes in the gut microbiota occurred before disease onset. The negative correlations between the involvement of UMNs and the concentrations of the metabolites might suggest that the inhibition of this metabolic pathway might lead to a better prognosis in ALS patients.
Improvement of nerve imaging speed with coherent anti-Stokes Raman scattering rigid endoscope using deep-learning noise reduction
Authors: Yamato Naoki , Niioka Hirohiko , Miyake Jun , Hashimoto Mamoru 
Published: September 2020

AbstractA coherent anti-Stokes Raman scattering (CARS) rigid endoscope was developed to visualize peripheral nerves without labeling for nerve-sparing endoscopic surgery. The developed CARS endoscope had a problem with low imaging speed, i.e. low imaging rate. In this study, we demonstrate that noise reduction with deep learning boosts the nerve imaging speed with CARS endoscopy. We employ fine-tuning and ensemble learning and compare deep learning models with three different architectures. In the fine-tuning strategy, deep learning models are pre-trained with CARS microscopy nerve images and retrained with CARS endoscopy nerve images to compensate for the small dataset of CARS endoscopy images. We propose using the equivalent imaging rate (EIR) as a new evaluation metric for quantitatively and directly assessing the imaging rate improvement by deep learning models. The highest EIR of the deep learning model was 7.0 images/min, which was 5 times higher than that of the raw endoscopic image of 1.4 images/min. We believe that the improvement of the nerve imaging speed will open up the possibility of reducing postoperative dysfunction by intraoperative nerve identification.
Association between dietary intake and the prevalence of tumourigenic bacteria in the gut microbiota of middle-aged Japanese adults
Authors: Watanabe Daiki , Murakami Haruka , Ohno Harumi , Tanisawa Kumpei , Konishi Kana , Tsunematsu Yuta , Sato Michio , Miyoshi Noriyuki , Wakabayashi Keiji , Watanabe Kenji , Miyachi Motohiko 
Published: September 2020

AbstractThe relative contribution of diet to colorectal cancer (CRC) incidence is higher than that for other cancers. Animal models have revealed that Escherichia coli containing polyketide synthase (pks+E. coli) in the gut participates in CRC development. The purpose of this cross-sectional study was to examine the relationship between dietary intake and the prevalence of pks+E. coli isolated from the microbiota in faecal samples of 223 healthy Japanese individuals. Dietary intake was assessed using a previously validated brief-type self-administered diet history questionnaire. The prevalence of pks+E. coli was evaluated using faecal samples collected from participants and specific primers that detected pks+E. coli. The prevalence of pks+E. coli was 26.9%. After adjusting for baseline confounders, the prevalence of pks+E. coli was negatively associated with the intake of green tea (odds ratio [OR], 0.59 [95% confidence interval (CI) 0.30–0.88] per 100 g/1,000 kcal increment) and manganese (OR, 0.43 [95% CI 0.22–0.85] per 1 mg/1,000 kcal increment) and was positively associated with male sex (OR, 2.27 [95% CI 1.05–4.91]). While futher studies are needed to validate these findings, these results provide insight into potential dietary interventions for the prevention of CRC.
Effects of wound dressings containing silver on skin and immune cells
Authors: Nešporová Kristina , Pavlík Vojtěch , Šafránková Barbora , Vágnerová Hana , Odráška Pavel , Žídek Ondřej , Císařová Natálie , Skoroplyas Svitlana , Kubala Lukáš , Velebný Vladimír 
Published: September 2020

AbstractWound dressings with silver have been shown to be cytotoxic in vitro. However, the extrapolation of this cytotoxicity to clinical settings is unclear. We applied dressings with various forms of silver on porcine skin ex vivo and investigated silver penetration and DNA damage. We assessed antimicrobial efficacy, cytotoxicity to skin cells, and immune response induced by the dressings. All dressings elevated the DNA damage marker γ-H2AX and the expression of stress-related genes in explanted skin relative to control. This corresponded with the amount of silver in the skin. The dressings reduced viability, induced oxidative stress and DNA damage in skin cells, and induced the production of pro-inflammatory IL-6 by monocytes. The oxidative burst and viability of activated neutrophils decreased. The amount of silver released into the culture medium varied among the dressings and correlated with in vitro toxicity. However, antimicrobial efficiencies did not correlate strongly with the amount of silver released from the dressings. Antimicrobial efficiency and toxicity are driven by the form of silver and the construction of dressings and not only by the silver concentration. The damaging effects of silver dressings in ex vivo skin highlight the importance of thorough in vivo investigation of silver dressing toxicity.
Video-assisted thoracoscopic lobectomy is feasible for selected patients with clinical N2 non-small cell lung cancer
Authors: Yun Jae Kwang , Lee Geun Dong , Choi Sehoon , Kim Hyeong Ryul , Kim Yong-Hee , Park Seung-Il , Kim Dong Kwan 
Published: September 2020

AbstractFew studies have evaluated the usefulness of video-assisted thoracoscopic surgery (VATS) for advanced-stage lung cancer. We aimed to evaluate the feasibility of VATS for treating clinical N2 (cN2) lung cancer. A retrospective cohort analysis was performed with data from 268 patients who underwent lobectomy for cN2 disease from 2007 to 2016. Using propensity score-based inverse probability of treatment weighting (IPTW), perioperative and long-term survival outcomes were compared. We performed VATS and open thoracotomy on 121 and 147 patients, respectively. Overall, VATS was preferred for patients with peripherally located tumors (p < 0.001). After IPTW-adjustment, all preoperative information became similar between the groups. Compared to thoracotomy, VATS was associated with shorter hospitalization (7.7 days vs. 9.1 days, p = 0.028), despite equivalent complete resection rates (92.6% vs. 90.5%, p = 0.488) and dissected lymph nodes (mean, 31.9 vs. 29.4, p = 0.100). On IPTW-adjusted analysis, overall survival (50.5% vs. 48.4%, p = 0.127) and recurrence-free survival (60.5% vs 44.6%, p = 0.069) at 5 years were also similar between the groups. Among selected patients with resectable cN2 disease and peripherally located tumors, VATS is feasible, associated with shorter hospitalization and comparable perioperative and long-term survival outcomes, compared with open thoracotomy.
Attenuating hypoxia driven malignant behavior in glioblastoma with a novel hypoxia-inducible factor 2 alpha inhibitor
Authors: Renfrow Jaclyn J. , Soike Michael H. , West James L. , Ramkissoon Shakti H. , Metheny-Barlow Linda , Mott Ryan T. , Kittel Carol A. , D’Agostino Ralph B. , Tatter Stephen B. , Laxton Adrian W. , Frenkel Mark B. , Hawkins Gregory A. , Herpai Denise , Sanders Stephanie , Sarkaria Jann N. , Lesser Glenn J. , Debinski Waldemar , Strowd Roy E. 
Published: September 2020

AbstractHypoxia inducible factor (HIFs) signaling contributes to malignant cell behavior in glioblastoma (GBM). We investigated a novel HIF2α inhibitor, PT2385, both in vitro, with low-passage patient-derived cell lines, and in vivo, using orthotopic models of glioblastoma. We focused on analysis of HIF2α expression in situ, cell survival/proliferation, and survival in brain tumor-bearing mice treated with PT2385 alone and in combination with standard of care chemoradiotherapy. HIF2α expression increased with glioma grade, with over half of GBM specimens HIF2α positive. Staining clustered in perivascular and perinecrotic tumor regions. Cellular phenotype including proliferation, viability, migration/invasion, and also gene expression were not altered after PT2385 treatment. In the animal model, PT2385 single-agent treatment did improve median overall survival compared to placebo (p = 0.04, n = 21) without a bioluminescence correlate (t = 0.67, p = 0.52). No difference in animal survival was seen in combination treatment with radiation (RT)/temozolomide (TMZ)/PT2385 (p = 0.44, n = 10) or mean tumor bioluminescence (t 1.13, p = 0.32). We conclude that HIF2α is a reasonable novel therapeutic target as expressed in the majority of glioblastomas in our cohort. PT2385 as a single-agent was efficacious in vivo, however, an increase in animal survival was not seen with PT2385 in combination with RT/TMZ. Further study for targeting HIF2α as a therapeutic approach in GBM is warranted.
Brimonidine-LAPONITE® intravitreal formulation has an ocular hypotensive and neuroprotective effect throughout 6 months of follow-up in a glaucoma animal model
Authors: Rodrigo M. J. , Cardiel M. J. , Fraile J. M. , Mendez-Martinez S. , Martinez-Rincon T. , Subias M. , Polo V. , Ruberte J. , Ramirez T. , Vispe E. , Luna C. , Mayoral J. A. , Garcia-Martin E. 
Published: September 2020

Brimonidine-LAPONITE® formulation is a potential intravitreal formulation for glaucoma treatment. It exhibits an early ocular hypotensive effect and functional and structural neuroretinal protection over 24 weeks of follow-up, after single injection.
Design of dual hormone blood glucose therapy and comparison with single hormone using MPC algorithm
Authors: Dias Cifha Crecil , Kamath Surekha , Vidyasagar Sudha 
Published: September 2020

The complete automated control and delivery of insulin and glucagon in type 1 diabetes is the developing technology for artificial pancreas. This improves the quality of life of a diabetic patient with the precise infusion. The amount of infusion of these hormones is controlled using a control algorithm, which has the prediction property. The control algorithm model predictive control (MPC) predicts one step ahead and infuses the hormones continuously according to the necessity for the regulation of blood glucose. In this research, the authors propose a MPC control algorithm, which is novel for a dual hormone infusion, for a mathematical model such as Sorenson model, and compare it with the insulin alone or single hormone infusion developed with MPC. Since they aim for complete automatic control and regulation, unmeasured disturbances at a random time are integrated and the performance evaluation is projected through statistical analysis. The blood glucose risk index (BGRI) and control variability grid analysis (CVGA) plot gives the additional evaluation for the comparative results of the two controllers claiming 88% performance by dual hormone evaluated through CVGA plot and 2.05 mg/dl average tracking error, 2.20 BGRI. The MPC developed for dual hormone significantly performs better and the time spent in normal glycaemia is longer while eliminating the risk of hyperglycaemia and hypoglycaemia.