bluuebunny/crossref_metadata_2025_split huggingface dataset:
The effects of combination treatments on drug resistance in chronic myeloid leukaemia: an evaluation of the tyrosine kinase inhibitors axitinib and asciminib
Authors: G. Lindström H. Jonathan , Friedman Ran 
Published: May 2020

Abstract
Background
Chronic myeloid leukaemia is in principle a treatable malignancy but drug resistance is lowering survival. Recent drug discoveries have opened up new options for drug combinations, which is a concept used in other areas for preventing drug resistance. Two of these are (I) Axitinib, which inhibits the T315I mutation of BCR-ABL1, a main source of drug resistance, and (II) Asciminib, which has been developed as an allosteric BCR-ABL1 inhibitor, targeting an entirely different binding site, and as such does not compete for binding with other drugs. These drugs offer new treatment options.

Methods
We measured the proliferation of KCL-22 cells exposed to imatinib–dasatinib, imatinib–asciminib and dasatinib–asciminib combinations and calculated combination index graphs for each case. Moreover, using the median–effect equation we calculated how much axitinib can reduce the growth advantage of T315I mutant clones in combination with available drugs. In addition, we calculated how much the total drug burden could be reduced by combinations using asciminib and other drugs, and evaluated which mutations such combinations might be sensitive to.

Results
Asciminib had synergistic interactions with imatinib or dasatinib in KCL-22 cells at high degrees of inhibition. Interestingly, some antagonism between asciminib and the other drugs was present at lower degrees on inhibition. Simulations revealed that asciminib may allow for dose reductions, and its complementary resistance profile could reduce the risk of mutation based resistance. Axitinib, however, had only a minor effect on T315I growth advantage.

Conclusions
Given how asciminib combinations were synergistic in vitro, our modelling suggests that drug combinations involving asciminib should allow for lower total drug doses, and may result in a reduced spectrum of observed resistance mutations. On the other hand, a combination involving axitinib was not shown to be useful in countering drug resistance.
LncRNA IGBP1-AS1/miR-24-1/ZIC3 loop regulates the proliferation and invasion ability in breast cancer
Authors: Chen Deqin , Fan Yangfan , Wan Fang 
Published: May 2020

Abstract
Background
Breast cancer (BC) is one of the malignant solid tumors with the highest morbidity in the world. Currently, the therapeutic outcome of different types of treatment can be unsatisfactory. Novel lncRNA biomarkers in BC remains to be further explored.

Methods
Different expression of lncRNAs among BC tissues and adjacent normal tissues were identified with microarray analyses. A series of in vivo and in vitro gain-of-function laboratory procedures were conducted to study the biological functions of IGBP1-AS1. The prognostic effects on IGBP1-AS1 survival were evaluated by using in situ hybridization and survival analysis. In addition, other experiments including RNA pull down analysis, RNA immunoprecipitation, luciferase reporter assays, and chromatin immunoprecipitation as well as validating assays conducted in vivo were applied to identify the target and regulatory mechanisms of IGBP1-AS1.

Results
Significant down-regulation of IGBP1-AS1 was discovered in the cell lines and tissues of BC. With respect to its biological function, overexpression of IGBP1-AS1 had inhibitory effects on the invasion and proliferation of BC cells in vivo as well as in vitro. Analysis of the samples obtained from BC patients indicated a positive effect of IGBP1-AS1 on survival outcomes. LncRNA IGBP1-AS1/miR-24-1/ZIC3 axis as a loop can regulate the proliferation and invasion of BC cells.

Conclusions
IGBP1-AS1 could have inhibitory impact on the invasion and proliferation of BC and may serve as a promising biomarker for BC.
Long non-coding RNA OIP5-AS1 suppresses multiple myeloma progression by sponging miR-27a-3p to activate TSC1 expression
Authors: Wang Yong , Wang Haibao , Ruan Jianwei , Zheng Wenbiao , Yang Zeyu , Pan Weiwei 
Published: May 2020

Abstract
Background
Multiple myeloma (MM) is a prevalent hematological malignancy. Long noncoding RNAs are correlated with the development of MM. In this project, the function of lncRNA opa interacting protein 5-antisense 1 (OIP5-AS1) in MM and the potential mechanistic pathway were explored.

Methods
The expression of OIP5-AS1, microRNA (miR)-27a-3p and tuberous sclerosis 1 (TSC1) was analyzed by quantitative real-time polymerase chain reaction (qRT-PCR) assay. Cell proliferation was assessed by Cell Counting Kit-8 (CCK-8) assay, colony formation assay and Bromodeoxyuridine (BrdU) staining. And cell apoptosis was evaluated by flow cytometry assay. Cell metastasis was assessed utilizing transwell assay. Western blot analysis was employed to detect protein level. The target relation between miR-27a-3p and OIP5-AS1 or TSC1 was confirmed via dual-luciferase reporter assay and RNA immunoprecipitation assay. Tumor xenograft assay was conducted to measure the function of OIP5-AS1 in vivo.

Results
The expression levels of OIP5-AS1 and TSC1 were decreased in MM, whereas miR-27a-3p was upregulated. High level of OIP5-AS1 could predict favourable prognosis of MM patients. Overexpression of OIP5-AS1 inhibited cell viability, colony formation ability, migration and invasion, induced cell cycle arrest in G1 phase and apoptosis of MM cells in vitro as well as repressed tumorigenesis in vivo. MiR-27a-3p was a target of OIP5-AS1, and reversed the impact of OIP5-AS1 on MM cells. MiR-27a-3p directly targeted TSC1. Silencing of miR-27a-3p repressed MM progression by elevating TSC1 expression. OIP5-AS1 upregulated TSC1 by sponging miR-27a-3p.

Conclusion
OIP5-AS1 repressed multiple myeloma progression by regulating miR-27a-3p/TSC1 axis.
Malaria in Venezuela: changes in the complexity of infection reflects the increment in transmission intensity
Authors: Pacheco M. Andreína , Forero-Peña David A. , Schneider Kristan A. , Chavero Melynar , Gamardo Angel , Figuera Luisamy , Kadakia Esha R. , Grillet María E. , Oliveira-Ferreira Joseli , Escalante Ananias A. 
Published: May 2020

AbstractBackgroundMalaria incidence has reached staggering numbers in Venezuela. Commonly, Bolívar State accounted for approximately 70% of the country cases every year. Most cases cluster in the Sifontes municipality, a region characterized by an extractive economy, including gold mining. An increase in migration to Sifontes, driven by gold mining, fueled a malaria spillover to the rest of the country and the region. Here samples collected in 2018 were compared with a previous study of 2003/2004 to describe changes in the parasites population structures and the frequency of point mutations linked to anti-malarial drugs.MethodsA total of 88Plasmodium falciparumand 94Plasmodium vivaxisolates were collected in 2018 and compared with samples from 2003/2004 (106P. falciparumand 104P. vivax). ForP. falciparum, mutations linked to drug resistance (Pfdhfr,Pfdhps, andPfcrt) and thePfk13gene associated with artemisinin delayed parasite clearance, were analysed. To estimate the multiplicity of infection (MOI), and performP. falciparumandP. vivaxpopulation genetic analyses, the parasites were genotyped by using eight standardized microsatellite loci.ResultsTheP. falciparumparasites are still harbouring drug-resistant mutations inPfdhfr,Pfdhps, andPfcrt. However, there was a decrease in the frequency of highly resistantPfdhpsalleles. Mutations associated with artemisinin delayed parasite clearance in thePfk13gene were not found. Consistent with the increase in transmission, polyclonal infections raised from 1.9% in 2003/2004 to 39% in 2018 inP. falciparumand from 16.3 to 68% inP. vivax. There is also a decrease in linkage disequilibrium. Bayesian clustering yields two populations linked to the time of sampling, showing that the parasite populations temporarily changed. However, the samples from 2003/2004 and 2018 have several alleles per locus in common without sharing multi-locus genotypes.ConclusionsThe frequency of mutations linked with drug resistance inP. falciparumshows only changes inPfdhps. Observations presented here are consistent with an increase in transmission from the previously circulating parasites. Following populations longitudinally, using molecular surveillance, provides valuable information in cases such as Venezuela with a fluid malaria situation that is affecting the regional goals toward elimination.
Characterisation of antibiotic resistance, virulence, clonality and mortality in MRSA and MSSA bloodstream infections at a tertiary-level hospital in Hungary: a 6-year retrospective study
Authors: Horváth Andrea , Dobay Orsolya , Sahin-Tóth Judit , Juhász Emese , Pongrácz Júlia , Iván Miklós , Fazakas Enikő , Kristóf Katalin 
Published: May 2020

Abstract
Background
Staphylococcus aureus bloodstream infections (BSI) cause significant morbidity and mortality due to the frequent antibiotic resistance, toxin and adhesin production of the bacterium. These characteristics differ significantly in methicillin resistant (MRSA) and methicillin sensitive S. aureus (MSSA) and also among isolates of different MRSA clones, contributing to the outcome of S. aureus bacteraemia.

Methods
In this study, all MRSA BSI isolates from Semmelweis University, Budapest, Hungary, isolated between 2011–2016 and the same number of matched MSSA (overall 306 isolates) were characterised in terms of antibiotic susceptibility, virulence genes, clonality and their association with all-cause 30-day mortality. Effect of patient related variables, such as age, gender and comorbidities were also investigated.

Results
ST22-MRSA-IV and ST5-MRSA-II were the most prevalent clones in our study. SCCmec I isolates showed the highest resistance rates and SCCmec II carried most virulence genes. Infections caused by SCCmec IV isolates were associated with the highest mortality rate (42.2%), despite the similar comorbidity rates of the different patient groups. All-cause 30-day mortality was 39.9% in the MRSA and 30.7% in the MSSA group. Increased teicoplanin MIC was associated with high mortality rate. Resistance to ciprofloxacin, erythromycin and clindamycin was common in MRSA, whereas MSSA isolates were more sensitive to all antibiotics with the exception of doxycycline. All MRSA isolates were sensitive to glycopeptides and linezolid; resistance to rifampicin and sulfamethoxazole-trimethoprim was low. MRSA isolates carried more adhesion genes, superantigens were more frequent in MSSA. Panton-Valentine leukocidin was found in 2.3% of the isolates.

Conclusion
This study provides insight into the clonal composition and associated mortality of BSI S. aureus isolates in Hungary. The results suggest that the outcome of the infection is determined by the antibiotic resistance, genotype of the bacterium, and patient-related factors; rather than the virulence factors carried by the bacteria.
Creation and validation of the 4-item BriefPCS-chronic through methodological triangulation
Authors: Walton David M. , Mehta Swati , Seo Wonjin , MacDermid Joy C. 
Published: May 2020

Abstract
Background
The Pain Catastrophizing Scale (PCS) is a widely used self-report tool to evaluate pain related catastrophizing. The PCS was developed using classical test theory and has been shown to be psychometrically sound among various populations. However, it’s current three subscales are rarely used in clinical practice, offering potential for an abbreviated version that reduces administrative burden and can be used to estimate full scale scores, yet is not bound by the inclusion of items from each subscale. Hence, the aim of the current study was to develop a unidimensional abbreviated version of the PCS through findings from qualitative, classical test theory, and newer Rasch analysis.

Methods
The current cross-sectional study used data from the Quebec Pain Registry (n = 5646) to obtain PCS scores of people seeking care at tertiary chronic pain centres. To develop an abbreviated unidimensional tool, items were removed based on triangulation of qualitative review of each item and response, corrected item-total correlations, and Rasch analysis. Confirmatory factor analysis was conducted on the final remaining items to confirm the tool was assessing a single latent construct (catastrophizing). Fit was assessed using the cumulative fit index (CFI), Tucker Lewis Index (TLI), and root-mean-squared error of approximation (RMSEA).

Results
After triangulation, a final abbreviated 4-item scale showed adequate model fit with a strong correlation (r > 0.95) with the original scale and properties that were stable across age, sex, cause, and medicolegal status. Additionally, the brief version addressed some problematic wording on some items on the original scale. Both the original and new abbreviated tool were associated with the Beck Depression Inventory and the Brief Pain Inventory at the same magnitude.

Conclusion
The abbreviated scale may allow for a decrease in administrator burden and greater clinical uptake when a quick screen for exaggerated negative orientation towards pain is needed.
Using Rasch measurement theory to assess the psychometric properties of a depressive symptoms scale in Norwegian adolescents
Authors: Kleppang Annette Løvheim , Steigen Anne Mari , Finbråten Hanne Søberg 
Published: May 2020

Abstract
Background
Scales measuring depressive symptoms in adolescents and adults are widely used for epidemiological purposes. The purpose of this study is to use Rasch measurement theory to examine the psychometric properties of a six-item scale intended to measure depressive symptoms in Norwegian adolescents.

Methods
The study is based on cross-sectional data from Ungdata, a survey conducted by the Norwegian Social Research Institute in cooperation with Regional Centres for Drug Rehabilitation in 2017. The target group comprised 13- to 19-years olds in Norway. Six items with four response categories, intended to measure depressive symptoms, were analysed. The analysis focused on invariance, including differential item functioning across gender and school levels. In addition, targeting, possible multidimensionality, response dependency, and the categorisation of the items were analysed.

Results
The scale measuring depressive symptoms shows good reliability and, on the whole, the items work well. However, one item, ‘had sleep problems’, clearly misfit and another, ‘worried too much about things’, works differently for males and females.

Conclusions
The scale has the potential to measure depressive symptoms in adolescents though there is room for improvement. To further improve the scale, the item concerning sleep problems should be rephrased.
A protective nesting association with native species counteracts biotic resistance for the spread of an invasive parakeet from urban into rural habitats
Authors: Hernández-Brito Dailos , Blanco Guillermo , Tella José L. , Carrete Martina 
Published: May 2020

Abstract
Background
Non-native species are often introduced in cities, where they take advantage of microclimatic conditions, resources provided by humans, and competitor/predator release to establish and proliferate. However, native communities in the surrounding rural or natural areas usually halt their spread through biotic resistance, mainly via top-down regulative processes (predation pressure). Here, we show an unusual commensal interaction between exotic and native bird species that favours the spread of the former from urban to rural habitats.

Results
We show how Monk parakeets Myiopsitta monachus, an invasive species often introduced in cities worldwide, associated for breeding with a much larger, native species (the white stork Ciconia ciconia) to reduce predation risk in central Spain, thus allowing their colonization of rural areas. Parakeets selected stork nests close to conspecifics and where breeding raptors were less abundant. Parakeets always flushed when raptors approached their nests when breeding alone, but stayed at their nests when breeding in association with storks. Moreover, when storks abandoned a nest, parakeets abandoned it in the following year, suggesting that storks actually confer protection against predators.

Conclusions
Our results show how a protective-nesting association between invasive and native species can counteract biotic resistance to allow the spread of an invasive species across non-urban habitats, where they may become crop pests. Monk parakeet populations are now growing exponentially in several cities in several Mediterranean countries, where they coexist with white storks. Therefore, management plans should consider this risk of spread into rural areas and favour native predators as potential biological controllers.
Longitudinal atherosclerotic changes after radio(chemo)therapy of hypopharyngeal carcinoma
Authors: Simonetto Cristoforo , Mayinger Michael , Ahmed Thamer , Borm Kai , Kundrát Pavel , Pigorsch Steffi , Kaiser Jan Christian , Combs Stephanie E. 
Published: May 2020

Abstract
Background
Radiotherapy treatment of head and neck cancer affects local arteries and increases the risk of stroke. This study aimed at a closer characterization of this damage and its development in time with a longitudinal study set up.

Methods
Male patients treated between 2011 and 2016 for hypopharyngeal carcinoma were identified from the in-house clinical data base. They were included into the study if besides the planning CT at least one additional CT image was available from follow-up (13 patients) or at least two MRI scans (16 patients of which 2 were already included). All patients received radiotherapy, and chemotherapy was administered to 16 patients. The time from the beginning of radiotherapy to the last available image ranged from 2 months to 4.5 years.
For six segments of the carotid arteries, the number and volume of atherosclerotic plaques were determined from the CT scans, and the intima media thickness from the MRI scans. Information on comorbid cardiovascular disease, hypertension and diabetes mellitus was retrieved from medical records.

Results
Total plaque volume rose from 0.25 cm3 before to 0.33 cm3 after therapy but this was not significant (p = 0.26). The mean number of plaques increased from 5.7 to 8.1 (p = 0.002), and the intima media thickened from 1.17 mm to 1.35 mm (p = 0.002). However, the mean intima media thickness practically did not change in patients with comorbid diabetes mellitus (p-value for homogeneity: 0.03). For patients without diabetes mellitus, dynamics of both plaque number and intima media thickness, was consistent with an increase until about one year after therapy and no further progression thereafter.

Conclusion
Our study confirmed the thickening of artery walls and the increase in the number of plaques. Results imply that definitive radiation damage to the artery walls can be determined not earlier than about one year after radiotherapy and there is no substantial deterioration thereafter. Reasons for the absence of an observable intima media thickening in patients with diabetes are unclear.
Furosemide stress test as a predictive marker of acute kidney injury progression or renal replacement therapy: a systemic review and meta-analysis
Authors: Chen Jia-Jin , Chang Chih-Hsiang , Huang Yen-Ta , Kuo George 
Published: May 2020

Abstract
Background
The use of the furosemide stress test (FST) as an acute kidney injury (AKI) severity marker has been described in several trials. However, the diagnostic performance of the FST in predicting AKI progression has not yet been fully discussed.

Methods
In accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, we searched the PubMed, Embase, and Cochrane databases up to March 2020. The diagnostic performance of the FST (in terms of sensitivity, specificity, number of events, true positive, false positive) was extracted and evaluated.

Results
We identified eleven trials that enrolled a total of 1366 patients, including 517 patients and 1017 patients for whom the outcomes in terms of AKI stage progression and renal replacement therapy (RRT), respectively, were reported. The pooled sensitivity and specificity results of the FST for AKI progression prediction were 0.81 (95% CI 0.74–0.87) and 0.88 (95% CI 0.82–0.92), respectively. The pooled positive likelihood ratio (LR) was 5.45 (95% CI 3.96–7.50), the pooled negative LR was 0.26 (95% CI 0.19–0.36), and the pooled diagnostic odds ratio (DOR) was 29.69 (95% CI 17.00–51.85). The summary receiver operating characteristics (SROC) with pooled diagnostic accuracy was 0.88. The diagnostic performance of the FST in predicting AKI progression was not affected by different AKI criteria or underlying chronic kidney disease. The pooled sensitivity and specificity results of the FST for RRT prediction were 0.84 (95% CI 0.72–0.91) and 0.77 (95% CI 0.64–0.87), respectively. The pooled positive LR and pooled negative LR were 3.16 (95% CI 2.06–4.86) and 0.25 (95% CI 0.14–0.44), respectively. The pooled diagnostic odds ratio (DOR) was 13.59 (95% CI 5.74–32.17), and SROC with pooled diagnostic accuracy was 0.86. The diagnostic performance of FST for RRT prediction is better in stage 1–2 AKI compared to stage 3 AKI (relative DOR 5.75, 95% CI 2.51–13.33).

Conclusion
The FST is a simple tool for the identification of AKI populations at high risk of AKI progression and the need for RRT, and the diagnostic performance of FST in RRT prediction is better in early AKI population.
Opposing needling for analgesia and rehabilitation after unilateral total knee arthroplasty: a randomized, sham-controlled trial protocol
Authors: Huang Hai , Song Xiuling , Zhao Ling , Zheng Lin , Xiao Lianbo , Chen Yuelai 
Published: May 2020

Abstract
Background
This randomized controlled clinical trial aims to evaluate the efficacy and safety of opposing needling in patients undergoing unilateral total knee arthroplasty (TKA). Opposing needling is one of the special needling methods used in acupuncture and moxibustion therapy. It involves needling acupoints on the contralateral side for pain management. Although, opposing needling is used for pain management in clinics, evidence to support its effectiveness as an analgesic after total knee arthroplasty is scant. We designed a randomized controlled clinical trial to evaluate efficacy and safety of opposing electroacupuncture (EA) in alleviating pain associated with unilateral total knee arthroplasty.

Methods/design
This is a protocol for a randomized controlled patient- and assessor-blinded trial with three parallel arms (A, opposing EA; B, operated side EA; C, sham EA). Yinlingquan (SP9), Yanglingquan (GB34), Futu (ST32), and Zusanli (ST36) acupoints are selected for all three groups. In group A, the healthy side will be treated with EA, while the operated side will be administered sham EA. In group B, the operated side will be treated with EA while on the healthy side sham EA will be used. For group C, sham EA will be used on both sides. All patients in the three groups will receive treatment once a day for 3 days. The post-operative pain measured using a visual analogue scale score (including pain while resting and being active) and the additional dose of the patient-controlled analgesic pump after operation will be recorded as the primary outcomes. Secondary outcomes such as knee function and swelling, range of motion (including active and passive range of motion), post-operative anxiety, and acupuncture tolerance will also be assessed.

Discussion
Opposing needling is a potential non-pharmacological treatment for relieving pain and improving functional rehabilitation after TKA, during which patients receive acupuncture on the healthy side rather than on the operated side. This sham controlled clinical trial, designed to evaluate efficacy and safety of opposing needling for patients after TKA, will provide evidence for pain management and functional rehabilitation after unilateral TKA.

Trial registration
ChiCTR, ChiCTR1800020297 (http://www.chictr.org.cn/edit.aspx?pid=34231&htm=4). Registered 22 December 2018.