bluuebunny/crossref_metadata_2025_split huggingface dataset:
Azoles resistance reversal by oridonin in Candida albicans
Authors: Shi Wenna , Chen Haisheng , Li Hui , Duan Cunxian , Song Chuanjie , Peng Zuoliang , Li Hui 
Published: April 2020

Abstract

Background

Candida albicans (C. albicans) is a yeast causing hazardous fungal infections with high mortality, especially accompanied by resistance to azole drugs (fluconazole, itraconazole and voriconazole). To overcome the azoles resistance of C. albicans, we explored the Oridonin (ORI) with three azole drugs mainly focused on the synergistic activity. In this study, C. albicans strains were obtained from cancer patients, and the reversal of drug resistance of azole-resistant C. albicans was further studied.
Methods

The synergistic antifungal activities of ORI and azoles were measured by checkerboard microdilution and time-kill assays. The resistance reversal mechanisms, inhibition of drug efflux and induction of apoptosis, were investigated by flow cytometry after Annexin V-FITC/PI co-staining. The expression levels of efflux pump related genes CDR1 and CDR2 were quantitatively detected by qRT-PCR.
Results

The azole-resistant isolates identified by checkerboard microdilution method and time-kill curves. The efflux pump inhibition assay with ORI showed that the MIC of fluconazole (128-fold), itraconazole (64-fold) and voriconazole (250-fold) decreased significantly. The upregulation of genes coding for CDR1 and CDR2 were confirmed by qPCR with respect to the housekeeping gene ACT1 in the resistant strain. The sensitizing effect of ORI on fluconazole in the treatment of C. albicans also includes promoting apoptosis. We demonstrated that the combination of azoles with ORI exerted potent synergism and further displayed that ORI could promote the sensitization to azoles for azoles-resistant C. albicans.
Conclusions

We speculate that the resistance to azoles depends on the overexpression of efflux pump and its related genes CDR1 and CDR2, which reduces the accessibility of antifungal agents to C. albicans. The discovery that ORI can effectively inhibit drug efflux and promote apoptosis may provide new insights and therapeutic strategies for overcoming the increasing azole resistance in C. albicans infections.
Simulated operation combined with patient-specific instrumentation technology is superior to conventional technology for supramalleolar osteotomy: A retrospective comparative study
Authors: Liu Hua , Wang Chenggong , Xu Can , Li Yusheng , Li Mingqing , Zhong Da , Wang Long 
Published: April 2020

Abstract

Background

Over the past seven years, our team has designed a simulated operation combined with patient-specific instrumentation (SO-PSI) assisted supramalleolar osteotomy (SMOT) method and applied it in the clinic. This study aimed to evaluate the differences between SO-PSI technology and conventional operation (CO) technology for SMOT in preoperative planning, intraoperative application, and postoperative curative effect.
Methods

We retrospectively analyzed SMOT data collected from our hospital between October 2014 and December 2018. Patients (n = 28) were enrolled and divided into CO (n = 17) and SO-PSI (n = 11) groups; mean follow-up time was 33.4 (range, 13 to 59) months. We statistically analyzed and compared perioperative data, accuracy of preoperative planning, and intraoperative application; difference between pre- and post-operative radiologic ankle angles; and changes in American Orthopaedic Foot & Ankle Society (AOFAS) score, visual analogue scale (VAS) score, range of ankle motion, and Takakura stage after surgery.
Results

All ankle alignments and positions were recovered for both groups. Compared with the CO group, the SO-PSI group had a shorter mean operating time and postoperative hospital stay, a decreased number of fluoroscopy examinations, lower albumin reduction, longer preoperative planning time and preoperative hospital stay, and increased hospitalization expenses. In the SO-PSI group, comparison of ankle angles at preoperative planning and postoperatively revealed good correlation, while this was not the case in the CO group. Mean tibial ankle center discrepancy for the SO-PSI group was 1.86 ± 1.06 mm. On follow-up, all radiologic parameters for the two groups improved significantly; however, the improvement of the tibial anterior surface angle and tibiotalar tilt angle for the SO-PSI group were more obvious than those for the CO group; AOFAS score, VAS score, ankle range of motion, and Takakura stage improved after surgery in both groups; however, the improvements in the SO-PSI group were greater than those in the CO group overall.
Conclusions

SO-PSI technology can facilitate accurate and rapid preoperative planning for SMOT. In general, compared with conventional technology, SO-PSI has advantages for preoperative planning, intraoperative application, and postoperative curative effect.
Global targetome analysis reveals critical role of miR-29a in pancreatic stellate cell mediated regulation of PDAC tumor microenvironment
Authors: Dey Shatovisha , Liu Sheng , Factora Tricia D , Taleb Solaema , Riverahernandez Primavera , Udari Lata , Zhong Xiaoling , Wan Jun , Kota Janaiah 
Published: April 2020

Abstract
Background
Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive forms of malignancies with a nearly equal incidence and mortality rates in patients. Pancreatic stellate cells (PSCs) are critical players in PDAC microenvironment to promote the aggressiveness and pathogenesis of the disease. Dysregulation of microRNAs (miRNAs) have been shown to play a significant role in progression of PDAC. Earlier, we observed a PSC-specific downregulation of miR-29a in PDAC pancreas, however, the mechanism of action of the molecule in PSCs is still to be elucidated. The current study aims to clarify the regulation of miR-29a in PSCs and identifies functionally important downstream targets that contribute to tumorigenic activities during PDAC progression.
Methods
In this study, using RNAseq approach, we performed transcriptome analysis of paired miR-29a overexpressing hPSC cells and controls. Enrichment analysis was performed with the identified differentially expressed genes (DEGs). miR-29a targets in the dataset were identified, which were utilized to create network interactions. Western blots were performed with the top candidate miR-29a targets in hPSC cells transfected with miR-29a mimic or scramble control.
Results
RNAseq analysis identified 202 differentially expressed genes, which included 19 downregulated direct miR-29a targets. Translational repression of eight key pro-tumorigenic and -fibrotic targets namely IGF-1, COL5A3, CLDN1, E2F7, MYBL2, ITGA6 and ADAMTS2 by miR-29a was observed in PSCs. Using pathway analysis, we find that miR-29a modulates effectors of IGF-1-p53 signaling in PSCs that may hinder carcinogenesis. We further observe a regulatory role of the molecule in pathways associated with PDAC ECM remodeling and tumor-stromal crosstalk, such as INS/IGF-1, RAS/MAPK, laminin interactions and collagen biosynthesis.
Conclusions
Together, our study presents a comprehensive understanding of miR-29a regulation of PSCs, and identifies essential pathways associated with PSC-mediated PDAC pathogenesis. The findings suggest an anti-tumorigenic role of miR-29a in the context of PSC-tumor cell crosstalk and advocates for the potential of the molecule in PDAC targeted therapies.
Metagenomic analysis reveals the shared and distinct features of the soil resistome across tundra, temperate prairie and tropical ecosystems
Authors: Qian Xun , Gunturu Santosh , Guo Jiarong , Chai Benli , Cole James R. , Gu Jie , Tiedje James 
Published: April 2020

Abstract
Background
Soil is likely the largest reservoir of antibiotic resistance genes (ARGs), but their distribution across soil resistomes of different ecosystems is unknown. We used a metagenomic approach to investigate ARG types and amounts in soil DNA of three native ecosystems: Alaskan tundra, US Midwestern prairie, and Amazon rainforest, as well as the effect of conversion of the latter two to agriculture and pasture, respectively.
Results
High diversity (242 ARG subtypes) and abundance (0.184–0.242 ARG copies per 16S rRNA gene copy) were observed irrespective of ecosystem, with multidrug resistance genes and efflux pump the dominant class and mechanism. We identified 55 “background ARGs” which were shared by all 26 soil metagenomes of all three ecosystems, which accounted for more than 81% of resistome abundance. No significant differences in both ARG diversity and abundance were observed between native prairie soil and adjacent long-term cultivated agriculture soil. Conversion of Amazon rainforest to pasture significantly increased soil ARG diversity, with eight ARGs significantly enriched. We chose 12 clinically important ARGs to evaluate at the sequence level and found them to be distinct from those in human pathogens, and when assembled they were even more dissimilar. Significant correlation was found between bacterial community structure and resistome profile, suggesting that variance in resistome profile was mainly driven by the bacterial community composition. There was also wide co-occurrence among ARGs in all samples.
Conclusions
Our results define common background ARGs, quantify resistance classes, provide sequence information suggestive of very low risk but also revealing resistance gene variants that might emerge in the future.
Dandelion Extract Relaxes Mouse Airway Smooth Muscle via the Blockade of VDLCC and NSCC Channels
Authors: Ping Zhao , Liu Jia , Ming Qian , Tian Di , He Jingwen , Yang Ziwei , Shen Jinhua , Liu Qinghua , Yang Xinzhou 
Published: April 2020

Abstract
Backgrond: Asthma is one of the intractable diseases recognized by the world medical community. The current widely used bronchodilators β2-adrenal receptor agonists for asthma have limited therapeutic effects, which make it necessary to develop novel drugs with increased efficacy but fewer side-effects for antiasthma treatments. In this study, we attempted to investigate the relaxing effects and mechanism of an ethyl acetate extract from dandelion (EAED) on mouse airway smooth muscle (ASM). Methods: The effects of EAED on the agonist-induced precontraction in mouse ASM were evaluated with force measurement. Mouse lung slices were conducted to study the effect of EAED on bronchial ASM. Intracellular Ca2+ concentration was measured using calcium imaging system. VDLCCs and NSCCs currents was measured by patch. Lung function of groups of healthy or asthmatic mice was assessed by forced oscillation technique (FOT). Results: EAED inhibits ACH-induced sustained contractions of the whole ASM by inhibiting VDLCC, NSCC and some unknown channels, decreases agonist-induced increasing cytosolic free Ca2+ concentration in ASMCs, blocks VDLCCs and NSCCs currents and relieve respiratory resistance of healthy and asthmatic mice. Conclusions: EAED may have potential beneficial effects on improving asthma attacks.
Time-restricted feeding and lower-extremity functioning in community-dwelling older adults
Authors: Estrada-DeLeón Daniela B. , Struijk Ellen A , Caballero Francisco Félix , Prieto Mercedes Sotos , Rodríguez-Artalejo Fernando , Lopez-Garcia Esther 
Published: April 2020

Abstract

Background: Time-restricted feeding, a specific form of intermittent fasting, has been associated with several possible health benefits including improved body composition, blood lipid levels and extended lifespan. However, it is unknown if time-restricted feeding confers a protective effect on the physical function of older adults. The aim of this study was to assess time-restricted feeding in association with performance-based lower-extremity function (LEF) in a large population of community-dwelling older adults.Methods: Cross-sectional study among 1,226 individuals ≥64 years from the Seniors-ENRICA-II cohort. In 2016-2017, habitual diet was assessed through a validated diet history. Fasting time was classified into the following categories: ≤9, 10-11, and ≥12hours/day, the latter being considered time-restricted feeding. Performance-based LEF was assessed with the Short Physical Performance Battery (SPPB).Results: After adjusting for potential confounders, a longer fasting period was associated with a higher likelihood of impaired LEF [odds ratio (OR) and 95% confidence intervals (CI) for the second and third categories: 2.27 (1.56-3.33); and 2.70 (1.80-4.04), respectively, considering the ≤9 hours/day fasting group as the reference category; p-trend <0.001]. When assessing each SPPB subtest separately, fasting time showed a significant association with balance impairment (OR for highest vs. lowest fasting time: 2.48; 95% CI: 1.51-4.08; p-trend= 0.001) and difficulty to rise from a chair (OR for highest vs. lowest fasting time: 1.47; 95% CI: 1.05-2.06; p-trend= 0.01).Conclusions: Time-restricted feeding was associated with a higher likelihood of impaired LEF, balance impairment, and difficulty to rise from a chair in older adults. These results need to be confirmed in further longitudinal studies.Trial registration: ClinicalTrials.gov NCT03541135. Registered 30 May 2018, retrospectively registered.
Predictors of School Students’ Leisure-Time Physical Activity: An Extended Trans-Contextual Model Using Bayesian Path Analysis
Authors: Polet Juho J. , Schneider Jekaterina , Hassandra Mary , Lintunen Taru , Laukkanen Arto , Hankonen Nelli , Hirvensalo Mirja , Tammelin Tuija H. , Hamilton Kyra , Hagger Martin S. 
Published: April 2020

Abstract
Background:The trans-contextual model (TCM) has been applied to identify the determinants of leisure-time physical activity participation in secondary school students. In the current study, the TCM was extended to include additional constructs that represent non-conscious, implicit processes that lead to leisure-time physical activity participation alongside the motivational and social cognition constructs from the TCM. The current study used baseline and follow-up data from an intervention study to test the extended TCM.Methods:The current study adopted a two-wave prospective design. Secondary-school students (N = 502) completed measures of perceived autonomy support from physical education (PE) teachers, autonomous motivation in PE and leisure-time contexts, social cognition constructs (attitudes, subjective norms, perceived behavioral control), intentions, trait self-control, habits, and past behavior all in a leisure-time physical activity context. Five weeks later, students (N = 298) completed a follow-up self-report measure of their leisure-time physical activity.Results:Bayesian path analyses supported two key premises of the model: perceived autonomous support predicted autonomous motivation in PE, and autonomous motivation in PE predicted autonomous motivation in leisure time. However, while both forms of autonomous motivation predicted social cognition constructs and intentions, they did not predict leisure-time physical activity participation. Trait self-control, attitudes, and past behavior were direct predictors of intentions and leisure-time physical activity participation. Specifying informative priors for key model relations using Bayesian analysis yielded greater precision for some of the estimates.Conclusions:Findings raise some questions on the efficacy of the original TCM, but highlight the value of extending the TCM to incorporate additional constructs representing non-conscious processes.
Currarino Syndrome in a China children’s health institute: on diagnosis and surgical treatment
Authors: Pang Wenbo , Chen Yajun , Peng Chunhui , Wang Kai , Qi Xiang , Wang Zengmeng , Wu Dongyang , Zhang Dan , Shen Qiulong 
Published: April 2020

Abstract
Background Currarino syndrome is a rare disease which needs multidisciplinary management. Misdiagnosis with mal-management is common in children. This study was to summarize the clinical features of children diagnosed with Currarino syndrome in a China institute, with an emphasis on diagnosis and surgical treatment, in order to aid in the diagnosis and determination of the optimal operative treatment. Results From 2016 to 2018, seven patients were diagnosed with Currarino syndrome in our department. One patient was male and six were female, with an admission age of 27.00(16.00, 44.00) months. In four patients, diagnosis of the presacral masses had been missed. Ultrasonography, plain sacral radiographs, contrast enemas and magnetic resonance imaging are necessary for the prompt diagnosis of this syndrome. The initial treatment involved a sagittal anorectoplasty and resection of the mass, followed by a defunctioning ostomy and closure of the stoma in a staged multidisciplinary approach. A limited sagittal route was chosen for the surgical treatment in this group. After closure of the ileostomy or colostomy, bowel function was satisfactory in all children. Conclusion Improved knowledge of the different clinical signs and symptoms of Currarino syndrome will result in appropriate imaging and prompt diagnosis. A protocol with rational timing of multidisciplinary surgical procedures may help to avoid undesirable outcomes. The limited sagittal route is available for effective operative treatment.
Sorafenib in the treatment of Hepatocellular carcinoma (HCC) patients with microvascular infiltration: a systematic review and meta-analysis
Authors: Gu Wang , Tong Zhong 
Published: April 2020

Abstract
Microvascular invasion has been shown to be an independent risk factor for liver cancer recurrence. Timely treatment can reduce the recurrence rate and prolong the total survival time. However, the effectiveness of sorafenib in treating HCC patients with microvascular invasion remains controversial. As of December 30, 2019, a comprehensive literature search has been conducted in PubMed, EMBASE, MEDLINE, web of science and Cochrane Library. A meta-analysis was conducted to assess the impact of sorafenib on mortality in HCC patients with microvascular involvement. Two researchers independently reviewed and cross-checked independent reports with sufficient information. Four studies were selected and reported 950 cancer events and 505 cancer deaths. The results showed that sorafenib could improve the survival rate of liver cancer patients with microvascular invasion (RR= 1.369;95% confidence interval (CI) ,1.193-1.570; P < 0.001). However, given the potential for residual confounding, the results should be interpreted with caution. Further prospective studies still need to confirm the prognostic benefits of sorafenib.
Beam complexity and monitor unit efficiency comparison in two different volumetric modulated arc therapy delivery using automated planning
Authors: Li Chengqiang , Tao Cheng , Bai Tong , Li Zhenjiang , Tong Ying , Zhu Jian , Yin Yong , Lu Jie 
Published: April 2020

Abstract
Background: To investigate the beam complexity and monitor unit（MU）efficiency issues for two different volumetric modulated arc therapy (VMAT) delivery technologies for patients with left-sided breast cancer (BC) and nasopharyngeal carcinoma (NPC). Methods: Twelve left-sided BC and seven NPC cases were enrolled in this study. Each delivered treatment plan was optimized in Pinnacle 3 treatment planning system with Auto-Planning module for Trilogy and Synergy systems. Similar planning dose objectives and beam configuration were used for each site in two different delivery systems to produce clinically acceptable plans. Beam complexity was evaluated in terms of segment area(SA), segment width(SW), leaf sequence variability(LSV), aperture area variability(AAV), modulation complexity score(MCS) based on MLC sequence and MU. Results: With similar plan quality, the average SAs for Trilogy plans were smaller than those for Synergy plans: 55.5 ± 21.3 cm 2 vs. 66.3 ± 17.9 cm 2 (p<0.05) for the NPC cases, and 100.7 ± 49.2 cm 2 vs. 108.5 ± 42.7 cm 2 (p<0.05) for BC cases, respectively. The SW was statistically significant for two delivery systems (NPC: 6.87±1.95cm vs.6.72±2.71cm, p < 0.05; BC: 8.84±2.56cm vs.8.09±2.63cm, p < 0.05). LSV was statistically significant smaller for Trilogy (NPC: 0.84±0.033 vs.0.86±0.033, p < 0.05; BC: 0.89±0.026 vs.0.90±0.26, p < 0.05). The mean AAV was statistically significant larger for Trilogy than Synergy (NPC: 0.18±0.064 vs.0.14±0.037, p < 0.05; BC: 0.46±0.15 vs.0.33±0.13, p < 0.05). The MCS values for the Trilogy were higher than those for the Synergy: 0.14 ± 0.016vs. 0.12 ± 0.017 (p<0.05) for the NPC cases, and 0.42 ± 0.106 vs. 0.30 ± 0.087(p<0.05) for the BC cases. Compared with Synergy plans, the average MU for Trilogy plans were larger: 828.6±74.1MU and 782.9±85.2MU (p>0.05) for the NPC cases, and 444.8±61.3MU and 393.8±75.3MU (p>0.05) for the BC cases. Conclusions: The pinnacle 3 Auto planning system can optimize BC and NPC plans to obtain the same plan quality using Trilogy and Synergy systems. We found that this two systems resulted in different SA, SW, LSV, AAV and MCS. As a result, we suggested that beam complexity should be considered in providing further methodologies while optimizing VMAT auto planning.
WITHDRAWN: Thoracic blockade in percutaneous hepatocellular carcinoma.
Authors: Glinka Lidia , Braczkowska Małgorzata , Kowalczyk Marek , Klepacki Łukasz , Zieliński Ewa , Batia Krzysztof , Osowiecka Karolina , Dyśko Łukasz , Iwanowski Maciej 
Published: April 2020

Abstract
Background Hepatocellular carcinoma (HCC) is a primary liver tumor that generally develops in a marsh-altered liver. Local ablation using radio frequency waves is the first-line treatment for patients with early onset of this cancer who cannot undergo radical surgery. This is a painful procedure and must be performed under deep intravenous analgosedation or general anesthesia. The method that appears to meet the anesthesiological and surgical requirements is thoracic paravertebral block.Aim of the study The main purpose of the study was to determine the efficacy and safety of paravertebral block compared to local perioperative anesthesia in patients who had percutaneous thermoablation as a treatment for HHC.Methods 30 patients enrolled in the treatment of hepatocellular carcinoma by percutaneous thermoablation were enrolled in the study. Two groups of patients were compared: group PVB - patients under paravertebral block anesthesia, group BB - patients under local anesthesia, without paravertebral block.Results The use of paravertebral blockade (PVB) did not significantly reduce the patient's concerns about the postoperative period, the ability to ask questions to the doctor, receive understandable information about anesthesia, reduce stress levels or increase the level of satisfaction with pain therapy in the postoperative period (p> 0.05). Patients significantly more often experienced pain during surgery without paravertebral block (p <0.001). Side effects of anesthesia occurred in both compared groups. They mainly concerned nausea and vomiting, which significantly more often occurred in the group without blockade (BB) and affected up to 60% of the respondents (p = 0.008). Significantly more often any painkillers were used among BB patients compared to PVB, respectively: immediately after surgery 53% vs 13% (p = 0.02), 1 hour after surgery 80% vs 27% (p = 0.003), 3h after surgery 80% vs 14% (p <0.001), 6h after surgery 60% vs 14% (p = 0.008), after 24h 47% vs 20% (p = 0.12).Conclusions The paravertebral block has proved to be a safe and well-tolerated and effective method of treating postoperative pain in patients with liver cancer treated by percutaneous thermoablation. Patients with PVB during the surgery and in the postoperative period had significantly less pain than in the control group.Trial Registration: NCT04241887 from January 27, 2020