bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effectiveness of a new sensorized videolaryngoscope for retraining on neonatal intubation in simulation environment
Authors: Covelli Alice , Bardelli Serena , Scaramuzzo Rosa T. , Sigali Emilio , Ciantelli Massimiliano , Del Pistoia Marta , Longo Alessia , Tognarelli Selene , Menciassi Arianna , Cuttano Armando 
Published: February 2020

Abstract
Background
In recent years, medical training has significantly increased the use of simulation for teaching and evaluation. The retraining of medical personnel in Italy is entrusted to the program of Continuous Education in Medicine, mainly based on theoretical training. The aim of this study is to assess whether the use of a new sensorized platform for the execution of the neonatal intubation procedure in simulation environment can complement theoretical retraining of experienced health professionals.

Methods
Neonatal intubation tests were performed using a commercial manikin and a modified video-laryngoscope by the addition of force and position sensors, which provide the user with feedback when the threshold is exceeded. Two categories carried out the simulation tests: anesthesiologists and pediatricians. The categories were divided into three groups each, and various configurations were tested: the first group of both specialists carried out the tests without feedback (i.e. control groups, gr. A and A1), the second groups received sound and visual feedback from the instrument (gr. B and B1) and the third ones had also the support of a physician expert in the use of the instrument (gr. C and C1). The instrumentation used by pediatricians was provided in a playful form, including a game with increasing difficulty levels.

Results
Both in the case with feedback only and in the case with humans support, anesthesiologists did not show a specific trend of improvement. Pediatricians, in comparison with anesthesiologists, showed a positive reaction to both the presence of feedback and that of experienced personnel. Comparing the performance of the two control groups, the two categories of experienced doctors perform similar forces. Pediatricians enjoyed the “Level Game”, through which they were able to test and confront themselves, trying to improve their own performance.

Conclusions
Our instrument is more effective when is playful and competitive, introducing something more than just a sound feedback, and allowing training by increasing levels. It is more effective if the users can adapt their own technique to the instrument by themselves, without any external help.
ESR1 mutations are frequent in newly diagnosed metastatic and loco-regional recurrence of endocrine-treated breast cancer and carry worse prognosis
Authors: Zundelevich Adi , Dadiani Maya , Kahana-Edwin Smadar , Itay Amit , Sella Tal , Gadot Moran , Cesarkas Karen , Farage-Barhom Sarit , Saar Efrat Glick , Eyal Eran , Kol Nitzan , Pavlovski Anya , Balint-Lahat Nora , Dick-Necula Daniela , Barshack Iris , Kaufman Bella , Gal-Yam Einav Nili 
Published: February 2020

Abstract
Background
Emerging mutations in the ESR1 gene that encodes for the estrogen receptor (ER) are associated with resistance to endocrine therapy. ESR1 mutations rarely exist in primary tumors (~ 1%) but are relatively common (10–50%) in metastatic, endocrine therapy-resistant cancers and are associated with a shorter progression-free survival. Little is known about the incidence and clinical implication of these mutations in early recurrence events, such as local recurrences or newly diagnosed metastatic disease.

Methods
We collected 130 archival tumor samples from 103 breast cancer patients treated with endocrine therapy prior to their local/metastatic recurrence. The cohort consisted of 41 patients having at least 1 sample from local/loco-regional recurrence and 62 patients with metastatic disease (of whom 41 newly diagnosed and 28 with advanced disease). The 5 most common ESR1 hotspot mutations (D538G, L536R, Y537S/N/C) were analyzed either by targeted sequencing or by droplet digital PCR. Progression-free survival (PFS), disease-free survival (DFS), and distant recurrence-free survival (DRFS) were statistically tested by Kaplan-Meier analysis.

Results
The prevalence of ESR1 mutations was 5/41 (12%) in newly diagnosed metastatic patients and 5/28 (18%) for advanced metastases, detected at allele frequency > 1%. All mutations in advanced metastases were detected in patients previously treated with both tamoxifen (TAM) and aromatase inhibitors (AI). However, in newly diagnosed metastatic patients, 4/5 mutations occurred in patients treated with TAM alone. PFS on AI treatment in metastatic patients was significantly shorter for ESR1 mutation carriers (p = 0.017). In the local recurrence cohort, ESR1 mutations were identified in 15/41 (36%) patients but only 4/41 (10%) were detected at allele frequency > 1%. Again, most mutations (3/4) were detected under TAM monotherapy. Notably, 1 patient developed ESR1 mutation while on neoadjuvant endocrine therapy. DFS and DRFS were significantly shorter (p = 0.04 and p = 0.017, respectively) in patients that had ESR1 mutations (> 1%) in their loco-regional recurrence tumor.

Conclusions
Clinically relevant ESR1 mutations are prevalent in newly diagnosed metastatic and local recurrence of endocrine-treated breast cancer. Since local recurrences are amenable to curative therapy, these mutations may inform the selection of subsequent endocrine therapies.
scAI: an unsupervised approach for the integrative analysis of parallel single-cell transcriptomic and epigenomic profiles
Authors: Jin Suoqin , Zhang Lihua , Nie Qing 
Published: February 2020

AbstractSimultaneous measurements of transcriptomic and epigenomic profiles in the same individual cells provide an unprecedented opportunity to understand cell fates. However, effective approaches for the integrative analysis of such data are lacking. Here, we present a single-cell aggregation and integration (scAI) method to deconvolute cellular heterogeneity from parallel transcriptomic and epigenomic profiles. Through iterative learning, scAI aggregates sparse epigenomic signals in similar cells learned in an unsupervised manner, allowing coherent fusion with transcriptomic measurements. Simulation studies and applications to three real datasets demonstrate its capability of dissecting cellular heterogeneity within both transcriptomic and epigenomic layers and understanding transcriptional regulatory mechanisms.
Bioconversion of ferulic acid attained from pineapple peels and pineapple crown leaves into vanillic acid and vanillin by Aspergillus niger I-1472
Authors: Tang Pei Ling , Hassan Osman 
Published: February 2020

AbstractThis study was conducted to evaluate the potential of pineapple peel (PP) and pineapple crown leaves (PCL) as the substrate for vanillic acid and vanillin production. About 202 ± 18 mg L−1 and 120 ± 11 mg L−1 of ferulic acid was produced from the PP and PCL respectively. By applied response surface methodology, the ferulic acid yield was increased to 1055 ± 160 mg L−1 by treating 19.3% of PP for 76 min, and 328 ± 23 mg L−1 by treating 9.9% of PCL for 36 min in aqueous sodium hydroxide solution at 120 °C. The results revealed that PP extract was better than PCL extract for vanillic acid and vanillin production. Furthermore, the experiment also proved that large volume feeding was more efficient than small volume feeding for high vanillic acid and vanillin yield. Through large volume feeding, about 7 ± 2 mg L−1 of vanillic acid and 5 ± 1 mg L−1 of vanillin was successfully produced from PP extract via Aspergillus niger fermentation.
Health coaching for promoting physical activity in low back pain patients: a secondary analysis on the usage and acceptance
Authors: Dejonghe Lea Anna Lisa , Rudolf Kevin , Becker Jennifer , Stassen Gerrit , Froboese Ingo , Schaller Andrea 
Published: February 2020

Abstract
Background
Multicomponent interventions combined with health coaching are widely recommended to improve a healthy lifestyle. The aim of the present study was to analyse the usage and acceptance of a multicomponent intervention (telephone, web and face-to-face coaching) for low back pain patients, and thereby gain an understanding of why this intervention was not as effective as expected.

Methods
A secondary analysis of a randomised controlled trial, aimed at promoting physical activity, was conducted. It was a cross-sectional study based on data of a multicomponent intervention group (baseline = 201 participants). For evaluating the usage and acceptance, descriptive statistics were applied.

Results
Over half (n = 118) of the patients participated at least once in the telephone coaching. Approximately half of the participants (44 of 90) rated the telephone coaching as “good”.
34 of 92 (37%) participants reported of visiting the web-platform. The web-platform was comprehensible for nearly one-quarter (n = 8 of 33) and very useful for one participant.
The face-to-face-contact was rated highly (range: 79.4–88.2 out of 100).

Conclusion
Usage of the telephone coaching approach was moderate with even fewer participants visiting the web-platform. In addition, these approaches were not rated as very useful. The acceptance of the face-to-face contact was high.
Since the usage and acceptance could influence the effectiveness, utilisation and acceptance studies might help to explain the reason for non-effective lifestyle interventions. Therefore, more studies analysing the usage and acceptance are needed. To improve the usage and acceptance, a stronger participatory orientation in the design of interventions and the integration of face-to-face contact could be helpful.
AICAR and nicotinamide treatment synergistically augment the proliferation and attenuate senescence-associated changes in mesenchymal stromal cells
Authors: Khorraminejad-Shirazi Mohammadhossein , Sani Mahsa , Talaei-Khozani Tahereh , Dorvash Mohammadreza , Mirzaei Malihe , Faghihi Mohammad Ali , Monabati Ahmad , Attar Armin 
Published: February 2020

Abstract
Background
Mesenchymal stromal cell (MSC) stemness capacity diminishes over prolonged in vitro culture, which negatively affects their application in regenerative medicine. To slow down the senescence of MSCs, here, we have evaluated the in vitro effects of 5-aminoimidazole-4-carboxamide ribonucleotide (AICAR), an AMPK activator, and nicotinamide (NAM), an activator of sirtuin1 (SIRT1).

Methods
Human adipose-derived MSCs were cultured to passage (P) 5. Subsequently, the cells were grown in either normal medium alone (control group), the medium supplemented with AICAR (1 mM) and NAM (5 mM), or in the presence of both for 5 weeks to P10. Cell proliferation, differentiation capacity, level of apoptosis and autophagy, morphological changes, total cellular reactive oxygen species (ROS), and activity of mTORC1 and AMPK were compared among different treatment groups.

Results
MSCs treated with AICAR, NAM, or both displayed an increase in proliferation and osteogenic differentiation, which was augmented in the group receiving both. Treatment with AICAR or NAM led to decreased expression of β-galactosidase, reduced accumulation of dysfunctional lysosomes, and characteristic morphologic features of young MSCs. Furthermore, while NAM administration could significantly reduce the total cellular ROS in aged MSCs, AICAR treatment did not. Moreover, AICAR-treated cells possess a high proliferation capacity; however, they also show the highest level of cellular apoptosis. The observed effects of AICAR and NAM were in light of the attenuated mTORC1 activity and increased AMPK activity and autophagy.

Conclusions
Selective inhibition of mTORC1 by AICAR and NAM boosts autophagy, retains MSCs’ self-renewal and multi-lineage differentiation capacity, and postpones senescence-associated changes after prolonged in vitro culture. Additionally, co-administration of AICAR and NAM shows an additive or probably a synergistic effect on cellular senescence.
Twenty years of research on the DFS70/LEDGF autoantibody-autoantigen system: many lessons learned but still many questions
Authors: Ortiz-Hernandez Greisha L. , Sanchez-Hernandez Evelyn S. , Casiano Carlos A. 
Published: February 2020

AbstractThe discovery and initial characterization 20 years ago of antinuclear autoantibodies (ANAs) presenting a dense fine speckled (DFS) nuclear pattern with strong staining of mitotic chromosomes, detected by indirect immunofluorescence assay in HEp-2 cells (HEp-2 IIFA test), has transformed our view on ANAs. Traditionally, ANAs have been considered as reporters of abnormal immunological events associated with the onset and progression of systemic autoimmune rheumatic diseases (SARD), also called ANA-associated rheumatic diseases (AARD), as well as clinical biomarkers for the differential diagnosis of these diseases. However, based on our current knowledge, it is not apparent that autoantibodies presenting the DFS IIF pattern fall into these categories. These antibodies invariably target a chromatin-associated protein designated as dense fine speckled protein of 70 kD (DFS70), also known as lens epithelium-derived growth factor protein of 75 kD (LEDGF/p75) and PC4 and SFRS1 Interacting protein 1 (PSIP1). This multi-functional protein, hereafter referred to as DFS70/LEDGF, plays important roles in the formation of transcription complexes in active chromatin, transcriptional activation of specific genes, regulation of mRNA splicing, DNA repair, and cellular survival against stress. Due to its multiple functions, it has emerged as a key protein contributing to several human pathologies, including acquired immunodeficiency syndrome (AIDS), leukemia, cancer, ocular diseases, and Rett syndrome. Unlike other ANAs, “monospecific” anti-DFS70/LEDGF autoantibodies (only detectable ANA in serum) are not associated with SARD and have been detected in healthy individuals and some patients with non-SARD inflammatory conditions. These observations have led to the hypotheses that these antibodies could be considered as negative biomarkers of SARD and might even play a protective or beneficial role. In spite of 20 years of research on this autoantibody-autoantigen system, its biological and clinical significance still remains enigmatic. Here we review the current state of knowledge of this system, focusing on the lessons learned and posing emerging questions that await further scrutiny as we continue our quest to unravel its significance and potential clinical and therapeutic utility.
Pre-test 68Ga-PSMA-ligand PET/CT positivity in early biochemical recurrent prostate cancer after radical prostatectomy—validation of a prediction model
Authors: Kraft Pia , Maurer Tobias , Gafita Andrei , Krönke Markus , Haller Bernhard , Weber Wolfgang A. , Eiber Matthias , Rauscher Isabel 
Published: February 2020

AbstractObjectivesThe aim of this study was the validation of a recently established comprehensive and compact prediction model for68Ga-PSMA-11-ligand positron-emission tomography (PET) positivity with an independent subsequent patient series.MethodsA total of 292 consecutive patients with early biochemical recurrence after radical prostatectomy and PSA values between 0.2 and 1 ng/ml who underwent68Ga-PSMA-11-ligand PET/computed tomography (CT) between January 2016 and June 2017 were retrospectively included. The cohort was divided into a very low PSA value (0.2–0.5 ng/ml,n= 151) and a low PSA value (> 0.5–1 ng/ml,n= 141) subgroup. First, pre-test positivity probabilities for each patient were calculated according to the previously published comprehensive prediction model using all clinical variables (PSA value, ISUP grade group, T- and N-stage, patient under androgen deprivation therapy (ADT), previous radiation therapy) and the compact model using just the most predictive factors PSA value, ADT, and grade group. Then, all68Ga-PSMA-11-ligand PET/CTs were analysed by one experienced nuclear medicine physician, and the results were correlated to the calculated pre-test probabilities.ResultsIn the very low PSA value subgroup, mean pre-test probability for positive findings in68Ga-PSMA-11-ligand PET/CT was 57% (95% CI 55–60%) according to the compact model and 59% (95% CI 56–61%) according to the comprehensive model. In the low PSA value subgroup, mean pre-test probability was 72% (95% CI 70–74%) in the compact model and 74% (95% CI 72–76%) in the comprehensive model. After image analysis, 59% (89/151) of the patients in the very low PSA value subgroup revealed positive imaging findings. Seventy-nine percent (112/141) of the patients in the low PSA value subgroup presented with positive findings in the68Ga-PSMA-11-ligand PET/CT. The accuracy (AUC) of the prediction models was 0.71 (95% CI 0.65–0.78) for the compact model and 0.74 (95% CI 0.68–0.80) for the comprehensive model.ConclusionExternal validation of the recently proposed prediction models showed a high concordance of the calculated pre-test probabilities and actual68Ga-PSMA-11-ligand PET/CT findings in the validation cohort confirming the prediction models’ ability to determine the presence of a positive lesion at68Ga-PSMA-11-ligand PET. However, the predictive accuracy of the nomogram itself is suboptimal and should be used with caution. Furthermore, the model’s generalizability may be hampered due to the study design (in-house validation). Nevertheless, given the limited health resources and the costs of hybrid imaging techniques, prediction models might be a benefit in patient selection.
MicroRNA gga-miR-200a-3p modulates immune response via MAPK signaling pathway in chicken afflicted with necrotic enteritis
Authors: Pham Thu Thao , Ban Jihye , Hong Yeojin , Lee Jiae , Vu Thi Hao , Truong Anh Duc , Lillehoj Hyun S. , Hong Yeong Ho 
Published: February 2020

AbstractMicroRNAs (miRNAs) are small non-coding RNAs that contribute to host immune response as post-transcriptional regulation. The current study investigated the biological role of the chicken (Gallus gallus) microRNA-200a-3p (gga-miR-200a-3p), using 2 necrotic enteritis (NE) afflicted genetically disparate chicken lines, 6.3 and 7.2, as well as the mechanisms underlying the fundamental signaling pathways in chicken. The expression of gga-miR-200a-3p in the intestinal mucosal layer of NE-induced chickens, was found to be upregulated during NE infection in the disease-susceptible chicken line 7.2. To validate the target genes, we performed an overexpression analysis of gga-miR-200a-3p using chemically synthesized oligonucleotides identical to gga-miR-200a-3p, reporter gene analysis including luciferase reporter assay, and a dual fluorescence reporter assay in cultured HD11 chicken macrophage cell lines. Gga-miR-200a-3p was observed to be a direct transcriptional repressor of ZAK, MAP2K4, and TGFβ2 that are involved in mitogen-activated protein kinase (MAPK) pathway by targeting the 3′-UTR of their transcripts. Besides, gga-miR-200a-3p may indirectly affect the expression of protein kinases including p38 and ERK1/2 at both transcriptional and translational levels, suggesting that this miRNA may function as an important regulator of the MAPK signaling pathway. Proinflammatory cytokines consisting of IL-1β, IFN-γ, IL-12p40, IL-17A, and LITAF belonging to Th1 and Th17-type cytokines, were upregulated upon gga-miR-200a-3p overexpression. These findings have enhanced our knowledge of the immune function of gga-miR-200a-3p mediating the chicken immune response via regulation of the MAPK signaling pathway and indicate that this miRNA may serve as an important biomarker of diseases in domestic animals.
CRISPR-PCDup: a novel approach for simultaneous segmental chromosomal duplication in Saccharomyces cerevisiae
Authors: Hassan Naim , Sasano Yu , Kimura Shunta , Easmin Farhana , Ekino Keisuke , Taguchi Hisataka , Harashima Satoshi 
Published: February 2020

AbstractIn our previous study, a novel genome engineering technology, PCR-mediated chromosome duplication (PCDup), was developed in Saccharomyces cerevisiae that enabled the duplication of any desired chromosomal region, resulting in a segmental aneuploid. From one round of transformation, PCDup can duplicate a single chromosomal region efficiently. However, simultaneous duplication of multiple chromosomal regions is not possible using PCDup technology, which is a serious drawback. Sequential duplication is possible, but this approach requires significantly more time and effort. Because PCDup depends upon homologous recombination, we reasoned that it might be possible to simultaneously create duplications of multiple chromosomal regions if we could increase the frequency of these events. Double-strand breaks have been shown to increase the frequency of homologous recombination around the break point. Thus, we aimed to integrate the genome editing tool CRISPR/Cas9 system, which induces double-strand breaks, with our conventional PCDup. The new method, which we named CRISPR-PCDup increased the efficiency of a single duplication by up to 30 fold. CRISPR-PCDup enabled the simultaneous duplication of long chromosomal segments (160 kb and 200 kb regions). Moreover, we were also able to increase the length of the duplicated chromosome by up to at least 400 kb, whereas conventional PCDup can duplicate up to a maximum of 300 kb. Given the enhanced efficiency of chromosomal segmental duplication and the saving in both labor and time, we propose that CRISPR-PCDup will be an invaluable technology for generating novel yeast strains with desirable traits for specific industrial applications and for investigating genome function in segmental aneuploid.
Effects of some flavonoids on the mycotoxin citrinin reduction by Monascus aurantiacus Li AS3.4384 during liquid-state fermentation
Authors: Wang Yanling , Gao Heng , Xie Jianhua , Li Xiujiang , Huang Zhibing 
Published: February 2020

AbstractMonascus can produce many beneficial metabolites; however, it can simultaneously also produce citrinin, which seriously limits its application. Therefore, reducing the production of citrinin is of great interest. Herein, Monascus aurantiacus Li AS3.4384 (MAL) was used to optimize the liquid-state fermentation process and investigate the effects of genistein and other flavonoids on citrinin, pigments, and biomass of MAL. Results showed that citrinin decreased by 80%, pigments and biomass increased by approximately 20% in 12 days with addition of 20.0 g/L rice powder as a carbon source and 2.0 g/L genistein during shaking liquid-state fermentation. Further, genistein, daidzein, luteolin, apigenin, quercetin, baicalein, kaempferol myricetin, and genistin exerted different effects on citrinin production by MAL, with genistein causing the highest reduction in citrinin production during liquid-state fermentation, possibly due to the presence of C5-OH, C4′-OH, and C7-OH. Therefore, genistein can be added to the fermentation process of Monascus to reduce citrinin.