bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effect of core materials for core fabrication for dental implants on in-vitro cytocompatibility of MC3T3-E1 cells
Authors: Park Jung-Hyun , Lee Hyun , Kang Seen-Young , Kim Junesun , Kim Ji-Hwan 
Published: December 2019

Abstract
Background
Despite the wide use of dental materials for CAD/CAM system in prosthetic treatment, the effect of the materials, which are used as dental implants core fabricated, on cells involved in dental implant osseointegration is uncertain. This study aimed to investigate and compare the effect of single core materials used for dental implants fabricated by the dental prostheses fabrication process and the CAD/CAM milling method on MC3T3-E1 cells.

Methods
The materials used for prostheses restoration in this experiment were Porcelain Fused Gold (P.F.G), Lithium disilicate glass ceramic (LiSi2), Zirconia (ZrO2), Nickel-Chromium (Ni-Cr) and Cobalt-Chromium (Co-Cr). MC3T3-E1 cells were cultured and used, the cell adhesion and morphology were observed and analyzed using confocal laser scanning microscopy (CLSM). Methoxyphenyl tetrazolium salt (MTS) and alkaline phosphatase (ALP) assay were used to observe the cell proliferation and differentiation.

Results
CLSM revealed irregular cell adhesion and morphology and the filopodia did not spread in the Ni-Cr specimen group. Significantly high cell proliferation was observed in the ZrO2 specimen group. The LiSi2 specimen group presented significantly high cell differentiation. Intergroup comparison of cell proliferation and differentiation between the Ni-Cr specimen group and all other specimen groups showed significant differences (p < .05).

Conclusion
Cell proliferation and differentiation were observed from the cores, which were fabricated with all specimen groups on cytocompatibility except the Ni-Cr specimen group.
Prognostic differences among patients with idiopathic interstitial pneumonias with acute exacerbation of varying pathogenesis: a retrospective study
Authors: Kato Motoyasu , Yamada Tomoko , Kataoka Shunichi , Arai Yuta , Miura Keita , Ochi Yusuke , Ihara Hiroaki , Koyama Ryo , Sasaki Shinichi , Takahashi Kazuhisa 
Published: December 2019

Abstract
Background
Acute exacerbation of chronic fibrosing idiopathic interstitial pneumonias (AE-IIPs) is associated with a high mortality rate. In 2016, an international working group proposed a revised diagnostic criteria for AE-IIPs, suggesting that it be classified as idiopathic or triggered. Many factors are known to trigger AE-IIPs, including surgery, infection, and drugs. However, it is unknown which AE-IIPs triggers have a worse prognosis. We aimed to investigate the prognosis of patients with various clinical types of AE-IIPs, particularly infection-triggered, non-infection triggered, and idiopathic AE-IIPs.

Methods
We retrospectively collected data from 128 chronic fibrosing IIPs (CF-IIPs) patients who were hospitalized by respiratory failure between April 2009 and March 2019 at Juntendo University Hospital. Among these patients, we evaluated 79 patients who developed AE-IIPs and 21 who developed pneumonia superimposed on CF-IIPs. Patients with AE-IIPs were classified into three types: idiopathic, infection-triggered, and non-infection-triggered AE-IIPs. We analyzed differences in patient characteristics, examination findings; level of serum markers, results of pulmonary function, and radiological findings, prior treatment for baseline CF-IIPs, and prognosis. We then evaluated the risk factor for early death (death within 30 days from the onset of AE-IIPs) associated with AE-IIPs.

Results
Among the patients who developed AE-IIPs, 34 were characterized as having idiopathic, 25 were characterized as having infection-triggered, and 20 were categorized as having non-infection-triggered AE-IIPs. Survival time for pneumonia superimposed on IIPs was significantly longer than that for any AE-IIPs. Survival time for bacterial pneumonia superimposed on CF-IIPs was significantly longer than that for AE-IIPs (for each idiopathic and all triggered IIPs). Thereafter, survival time for infection-triggered was significantly longer than for idiopathic or non-infection-triggered AE-IIPs. The mortality rate was significantly lower in infection-triggered AE-IIPs than in other types of AE-IIPs. Furthermore, the incidence of infection-triggered AE-IIPs in winter was significantly higher than that in other seasons. Moreover, the clinical AE-IIPs types and radiological findings at AE-IIP onset were significant risk factors for AE-IIPs-induced early death.

Conclusions
Our findings suggest that patients with infection-triggered AE-IIPs can expect a better prognosis than can patients with other clinical types of AE-IIPs.
Clinical characteristics and treatment outcomes of patients with macrolide-resistant Mycobacterium avium complex pulmonary disease: a systematic review and meta-analysis
Authors: Park Youngmok , Lee Eun Hye , Jung Inkyung , Park Goeun , Kang Young Ae 
Published: December 2019

Abstract
Background
Macrolide is a key drug in the treatment of Mycobacterium avium complex pulmonary disease (MAC-PD). Macrolide-resistant MAC is gaining importance, but there are little data in clinical characteristics and treatment outcomes of macrolide-resistant MAC-PD (MR-MAC-PD).

Methods
We performed a systematic review and meta-analysis of published studies reporting clinical characteristics and treatment outcomes of patients with MR-MAC-PD. Risk of bias was assessed using the modified Newcastle-Ottawa Scale.

Results
Nine studies (seven retrospective and two prospective) comprising 319 patients were identified through a database search. Around 73% were women, and 52% had the fibrocavitary form. Pooled sputum culture conversion rate after combined multiple antibiotics or surgical resection was 21% (95% confidence interval [CI], 14–30%), and the one-year all-cause mortality was 10% (95% CI, 5–20%). There was no significant difference in treatment outcomes between nodular bronchiectatic and fibrocavitary types.

Conclusions
Even combination therapy with fluoroquinolone, aminoglycoside, and surgical resection, the treatment outcomes of MR-MAC-PD were poor. The investigation of new treatment modalities is urgent.
Exchange protein directly activated by cAMP (Epac) protects against airway inflammation and airway remodeling in asthmatic mice
Authors: Chen Yi-fei , Huang Ge , Wang Yi-min , Cheng Ming , Zhu Fang-fang , Zhong Jin-nan , Gao Ya-dong 
Published: December 2019

Abstract
Background
β2 receptor agonists induce airway smooth muscle relaxation by increasing intracellular cAMP production. PKA is the traditional downstream signaling pathway of cAMP. Exchange protein directly activated by cAMP (Epac) was identified as another important signaling molecule of cAMP recently. The role of Epac in asthmatic airway inflammation and airway remodeling is unclear.

Methods
We established OVA-sensitized and -challenged acute and chronic asthma mice models to explore the expression of Epac at first. Then, airway inflammation and airway hyperresponsiveness in acute asthma mice model and airway remodeling in chronic asthma mice model were observed respectively after treatment with Epac-selective cAMP analogue 8-pCPT-2′-O-Me-cAMP (8pCPT) and Epac inhibitor ESI-09. Next, the effects of 8pCPT and ESI-09 on the proliferation and apoptosis of in vitro cultured mouse airway smooth muscle cells (ASMCs) were detected with CCK-8 assays and Annexin-V staining. Lastly, the effects of 8pCPT and ESI-09 on store-operated Ca2+ entry (SOCE) of ASMCs were examined by confocal Ca2+ fluorescence measurement.

Results
We found that in lung tissues of acute and chronic asthma mice models, both mRNA and protein expression of Epac1 and Epac2, two isoforms of Epac, were lower than that of control mice. In acute asthma mice model, the airway inflammatory cell infiltration, Th2 cytokines secretion and airway hyperresponsiveness were significantly attenuated by 8pCPT and aggravated by ESI-09. In chronic asthma mice model, 8pCPT decreased airway inflammatory cell infiltration and airway remodeling indexes such as collagen deposition and airway smooth muscle cell proliferation, while ESI-09 increased airway inflammation and airway remodeling. In vitro cultured mice ASMCs, 8pCPT dose-dependently inhibited, whereas ESI-09 promoted ASMCs proliferation. Interestingly, 8pCPT promoted the apoptosis of ASMCs, whereas ESI-09 had no effect on ASMCs apoptosis. Lastly, confocal Ca2+ fluorescence examination found that 8pCPT could inhibit SOCE in ASMCs at 100 μM, and ESI-09 promoted SOCE of ASMCs at 10 μM and 100 μM. In addition, the promoting effect of ESI-09 on ASMCs proliferation was inhibited by store-operated Ca2+ channel blocker, SKF-96365.

Conclusions
Our results suggest that Epac has a protecting effect on asthmatic airway inflammation and airway remodeling, and Epac reduces ASMCs proliferation by inhibiting SOCE in part.
Circulating tumor cells in precision oncology: clinical applications in liquid biopsy and 3D organoid model
Authors: Yang Chang , Xia Bai-Rong , Jin Wei-Lin , Lou Ge 
Published: December 2019

AbstractCirculating tumor cells (CTCs) are a rare subset of cells found in the blood of patients with solid tumors, which function as a seed for metastases. Cancer cells metastasize through the bloodstream either as single migratory CTCs or as multicellular groupings—CTC clusters. The CTCs preserve primary tumor heterogeneity and mimic tumor properties, and may be considered as clinical biomarker, preclinical model, and therapeutic target. The potential clinical application of CTCs is being a component of liquid biopsy. CTCs are also good candidates for generating preclinical models, especially 3D organoid cultures, which could be applied in drug screening, disease modeling, genome editing, tumor immunity, and organoid biobanks. In this review, we summarize current knowledge on the value and promise of evolving CTC technologies and highlight cutting-edge research on CTCs in liquid biopsy, tumor metastasis, and organoid preclinical models. The study of CTCs offers broad pathways to develop new biomarkers for tumor patient diagnosis, prognosis, and response to therapy, as well as translational models accelerating oncologic drug development.
Markers of sulfadoxine–pyrimethamine resistance in Eastern Democratic Republic of Congo; implications for malaria chemoprevention
Authors: van Lenthe Marit , van der Meulen Renske , Lassovski Maryvonne , Ouabo Adelaide , Bakula Edwige , Badio Colette , Cibenda Deogratias , Okell Lucy , Piriou Erwan , Grignard Lynn , Lanke Kjerstin , Rao Bhargavi , Bousema Teun , Roper Cally 
Published: December 2019

Abstract
Background
Sulfadoxine–pyrimethamine (SP) is a cornerstone of malaria chemoprophylaxis and is considered for programmes in the Democratic Republic of Congo (DRC). However, SP efficacy is threatened by drug resistance, that is conferred by mutations in the dhfr and dhps genes. The World Health Organization has specified that intermittent preventive treatment for infants (IPTi) with SP should be implemented only if the prevalence of the dhps K540E mutation is under 50%. There are limited current data on the prevalence of resistance-conferring mutations available from Eastern DRC. The current study aimed to address this knowledge gap.

Methods
Dried blood-spot samples were collected from clinically suspected malaria patients [outpatient department (OPD)] and pregnant women attending antenatal care (ANC) in four sites in North and South Kivu, DRC. Quantitative PCR (qPCR) was performed on samples from individuals with positive and with negative rapid diagnostic test (RDT) results. Dhps K450E and A581G and dhfr I164L were assessed by nested PCR followed by allele-specific primer extension and detection by multiplex bead-based assays.

Results
Across populations, Plasmodium falciparum parasite prevalence was 47.9% (1160/2421) by RDT and 71.7 (1763/2421) by qPCR. Median parasite density measured by qPCR in RDT-negative qPCR-positive samples was very low with a median of 2.3 parasites/µL (IQR 0.5–25.2). Resistance genotyping was successfully performed in RDT-positive samples and RDT-negative/qPCR-positive samples with success rates of 86.2% (937/1086) and 55.5% (361/651), respectively. The presence of dhps K540E was high across sites (50.3–87.9%), with strong evidence for differences between sites (p < 0.001). Dhps A581G mutants were less prevalent (12.7–47.2%). The dhfr I164L mutation was found in one sample.

Conclusions
The prevalence of the SP resistance marker dhps K540E exceeds 50% in all four study sites in North and South Kivu, DRC. K540E mutations regularly co-occurred with mutations in dhps A581G but not with the dhfr I164L mutation. The current results do not support implementation of IPTi with SP in the study area.
Moderate maternal separation mitigates the altered synaptic transmission and neuronal activation in amygdala by chronic stress in adult mice
Authors: Qin Xia , He Ye , Wang Na , Zou Jia-Xin , Zhang Yong-Mei , Cao Jun-Li , Pan Bing-Xing , Zhang Wen-Hua 
Published: December 2019

AbstractExposure to moderate level of stress during the perinatal period helps the organisms to cope well with stressful events in their later life, an effect known as stress inoculation. Amygdala is one of the kernel brain regions mediating stress-coping in the brain. However, little is known about whether early life stress may affect amygdala to have its inoculative effect. Here, we observed that moderate maternal separation (MS) from postnatal day 3 to day 21 (D3–21, 1 h per day) significantly alleviated the increased anxiety-like behavior induced by chronic social defeat stress (CSDS) in adulthood, suggesting an obvious inoculative effect of moderate MS. Further studies revealed that MS prevented CSDS-evoked augmentation of glutamatergic transmission onto principal neurons (PNs) in the basolateral amygdala (BLA) by inhibiting presynaptic glutamate release. By contrast, it did not affect GABAergic transmission in BLA PNs, as indicated by unaltered frequency and amplitude of miniature inhibitory postsynaptic currents (mIPSCs). Moreover, the CSDS-induced increase of neuronal excitability was also mitigated by MS in BLA PNs. In conclusion, our results suggest that MS may have its inoculative effect through alleviating the influences of later life stress on the glutamatergic transmission and neuronal activity in amygdala neurons.
Whole genome DNA sequencing provides an atlas of somatic mutagenesis in healthy human cells and identifies a tumor-prone cell type
Authors: Franco Irene , Helgadottir Hafdis T. , Moggio Aldo , Larsson Malin , Vrtačnik Peter , Johansson Anna , Norgren Nina , Lundin Pär , Mas-Ponte David , Nordström Johan , Lundgren Torbjörn , Stenvinkel Peter , Wennberg Lars , Supek Fran , Eriksson Maria 
Published: December 2019

AbstractBackgroundThe lifelong accumulation of somatic mutations underlies age-related phenotypes and cancer. Mutagenic forces are thought to shape the genome of aging cells in a tissue-specific way. Whole genome analyses of somatic mutation patterns, based on both types and genomic distribution of variants, can shed light on specific processes active in different human tissues and their effect on the transition to cancer.ResultsTo analyze somatic mutation patterns, we compile a comprehensive genetic atlas of somatic mutations in healthy human cells. High-confidence variants are obtained from newly generated and publicly available whole genome DNA sequencing data from single non-cancer cells, clonally expanded in vitro. To enable a well-controlled comparison of different cell types, we obtain single genome data (92% mean coverage) from multi-organ biopsies from the same donors. These data show multiple cell types that are protected from mutagens and display a stereotyped mutation profile, despite their origin from different tissues. Conversely, the same tissue harbors cells with distinct mutation profiles associated to different differentiation states. Analyses of mutation rate in the coding and non-coding portions of the genome identify a cell type bearing a unique mutation pattern characterized by mutation enrichment in active chromatin, regulatory, and transcribed regions.ConclusionsOur analysis of normal cells from healthy donors identifies a somatic mutation landscape that enhances the risk of tumor transformation in a specific cell population from the kidney proximal tubule. This unique pattern is characterized by high rate of mutation accumulation during adult life and specific targeting of expressed genes and regulatory regions.
Elucidating vaginal fistulas on CT and MRI
Authors: Tonolini Massimo 
Published: December 2019

AbstractVaginal fistulas (VF) represent abnormal communications between the vagina and either the distal portion of the digestive system or the lower urinary tract, but lack an accepted classification and standardised terminology. Regardless of the underlying cause, these uncommon disorders result in profound physical, psychological, sexual and social distress to the patients.Since diagnosis of VF is challenging at gynaecologic examination, ano-proctoscopy and urethro-cystoscopy, imaging is crucial to confirm the fistula, to visualise its site, course and involved organ, and to characterise the underlying disease. The traditional conventional radiographic studies provided limited cross-sectional information and are nowadays largely replaced by CT and MRI studies.Aiming to provide radiologists with an increased familiarity with VF, this pictorial paper summarises their clinical features, pathogenesis and therapeutic approach, and presents the appropriate CT and MRI acquisition and interpretation techniques that vary according to the anatomic site and termination of the fistula. The current role of state-of-the art CT and MRI is presented with examples regarding both entero- (involving the colon, rectum and anus) and urinary (connecting the bladder, distal ureter or urethra) VF. The resulting combined anatomic and functional cross-sectional information is crucial to allow a correct therapeutic choice and surgical planning.
PAMAM-cRGD mediating efficient siRNA delivery to spermatogonial stem cells
Authors: Li Tianjiao , Chen Qiwen , Zheng Yi , Zhang Pengfei , Chen Xiaoxu , Lu Junna , Lv Yinghua , Sun Shiguo , Zeng Wenxian 
Published: December 2019

Abstract
Background
Spermatogonial stem cells (SSCs) are the cornerstone of sperm production and thus perpetual male fertility. In clinics, transplantation of patient’s own SSCs into testes is a promising technique to restore fertility when male germ cells have been depleted by gonadotoxic therapies. Auto-transplantation of genetically modified SSCs even has the potential to treat male infertility caused by genetic mutations. However, SSCs are refractory to transfection approaches. Poly(amidoamine) (PAMAM) dendrimers have the unique three-dimensional architecture, surface charge, and high density of surface groups that are suitable for ligand attachment, thereby facilitating target delivery. The goal of this study was to elucidate whether PAMAM dendrimers can efficiently deliver short interfering RNAs (siRNAs) to SSCs.

Methods and results
We introduced cyclic arginine-glycine-aspartic acid (cRGD) peptides to the fifth generation of PAMAM dendrimers (G5) to generate PAMAM-cRGD dendrimers (G5-cRGD). The characterization of G5-cRGD was detected by Fourier transform infrared spectroscope (FTIR), transmission electron microscope (TEM), and the Cell Counting Kit-8 (CCK-8) assay. Confocal microscopy and flow cytometry were used to evaluate the delivery efficiency of siRNA by G5-cRGD to SSCs. The results showed that G5-cRGD encompassing siRNA could self-assemble into spherical structures with nanoscale size and possess high transfection efficiency, excellent endosomal escape ability, and low cytotoxicity, superior to a commercial transfection reagent Lipofectamine® 2000. Moreover, we demonstrated that G5-cRGD efficiently delivered siRNAs and triggered gene silencing.

Conclusions
This study thus provides a promising nanovector for siRNA delivery in SSCs, facilitating the future clinical application of SSC auto-transplantation with genetically modified cells with a hope to cure male infertility that is caused by genetic disorders.
A comprehensive proteomics profiling identifies NRP1 as a novel identity marker of human bone marrow mesenchymal stromal cell-derived small extracellular vesicles
Authors: Munshi Afnan , Mehic Jelica , Creskey Marybeth , Gobin Jonathan , Gao Jun , Rigg Emma , Muradia Gauri , Luebbert Christian C. , Westwood Carole , Stalker Andrew , Allan David S. , Johnston Michael J. W. , Cyr Terry , Rosu-Myles Michael , Lavoie Jessie R. 
Published: December 2019

Abstract
Background
Clinical applications have shown extracellular vesicles (EVs) to be a major paracrine effector in therapeutic responses produced by human mesenchymal stromal/stem cells (hMSCs). As the regenerative capacity of EVs is mainly ascribed to the transfer of proteins and RNA composing its cargo, and to the activity attributed by the protein surface markers, we sought to profile the protein composition of small EVs released from hMSCs to identify hMSC-EV biomarkers with potential clinical relevance.

Methods
Small EVs were produced and qualified from five human bone marrow MSC donors at low passage following a 48-h culture in exosome-depleted medium further processed by steps of centrifugation, filtration, and precipitation. Quantitative proteomic analysis comparing the protein profile of the EVs released from hMSCs and their parental cell was conducted using tandem mass tag labeling combined to mass spectrometry (LC-MS/MS) to identify enriched EV protein markers.

Results
Nanoparticle tracking analysis showed no differences in the EV concentration and size among the five hMSC donors (1.83 × 1010 ± 3.23 × 109/mL), with the mode particle size measuring at 109.3 ± 5.7 nm. Transmission electron microscopy confirmed the presence of nanovesicles with bilayer membranes. Flow cytometric analysis identified commonly found exosomal (CD63/CD81) and hMSC (CD105/CD44/CD146) markers from released EVs in addition to surface mediators of migration (CD29 and MCSP). Quantitative proteomic identified 270 proteins significantly enriched by at least twofold in EVs released from hMSCs as compared to parental hMSCs, where neuropilin 1 (NRP1) was identified among 21 membrane-bound proteins regulating the migration and invasion of cells, as well as chemotaxis and vasculogenesis. Validation by western blot of multiple batches of EVs confirmed consistent enrichment of NRP1 in the nanovesicles released from all five hMSC donors.

Conclusion
The identification and verification of NRP1 as a novel enriched surface marker from multiple batches of EVs derived from multiple hMSC donors may serve as a biomarker for the assessment and measurement of EVs for therapeutic uses.