bluuebunny/crossref_metadata_2025 huggingface dataset:
Latent structure, measurement invariance, and reliability of an Arabic version of the Short Health Anxiety Inventory
Authors: Alshayea Ahmad Kassab
Published: April 2020

The Short Health Anxiety Inventory (SHAI) is a well-established, self-report measure of health anxiety (HA). However, no psychometrically adequate Arabic-speaking version of this measure is yet available. This study was therefore designed to provide an Arabic version of the SHAI and assess its latent structure, measurement invariance across gender, and internal consistency reliability. Forty hundred and twenty-one Saudis completed the Arabic SHAI online (68.65% women), mean age 25.90, and standard deviation 6.65. Exploratory and confirmatory factor analyses in different subsamples suggested a 2-factor solution: (1) illness likelihood (IL) with 13 items and (2) negative consequences (NC) with 4 items. This structure was found invariant across gender. Cronbach’s α for the full scale, IL, and NC were .85, .83, and .77, respectively. Corrected item–total correlations for all items ranged from .35 to .68. Performance on the scale did not appear to correlate with gender, while age associated weakly but statistically significant with the total score and IL factor. The present Arabic SHAI appears to be a psychometrically promising tool for the assessment of HA. Further investigations of the scale psychometrics, particularly using a paper-and-pencil format, and clinical utility are warranted.
Study, Design, and Rationale of Noncommunicable Diseases in Nepal (NCD Nepal) Study: A Community-Based Prospective Epidemiological and Implementation Study in Rural Nepal
Authors: Neupane Gagan , Acharya Sameer , Bhattarai Manoj , Upadhyay Ashish , Belbase Bishal , Bhandari Manoj , Pandeya Drona , Pokharel Shatakshi , Ghimire Sulochana , Thapa Gorakh , Karmacharya Biraj , Bhatt Madan Raj , Spertus John A , Neupane Dinesh , Timsina Lava , Pokharel Yashashwi
Published: April 2020

Background

Noncommunicable diseases (NCDs) are the leading causes of deaths globally. Currently, there are limited high-quality data on the epidemiology and usefulness of community-based screening and treatment of NCDs in low-to-middle-income countries (LMIC), like Nepal. We describe the protocol of a community-based, longitudinal epidemiological study of screening and management of NCDs in rural Nepal.

Methods

We organize monthly mobile health clinics to screen NCDs among 40- to 75-year-old residents from municipal subdivision wards 3, 4, 6, and 7 of Ghorahi submetropolitan city, Dang, Nepal (approximately 406 km west of the capital, Kathmandu). We estimate a total of 7052 eligible participants. After obtaining informed consent, trained personnel will collect sociodemographic and lifestyle data, medical, medication, and family history using validated questionnaires, plus anthropometric measures and capillary glucose levels. We will screen for hypertension, diabetes, obesity, dyslipidemia, tobacco and alcohol use, self-reported physical activity, dietary habits, cardiovascular disease, stroke, chronic lung disease, cancer, and chronic kidney disease. We will also check hemoglobin A1C, lipid panel, serum creatinine, sodium, potassium, urine dipstick, and urine albumin-to-creatinine ratio in high-risk participants. We will offer lifestyle counseling, pharmacotherapy or refer to higher level care, where appropriate; routinely follow participants with NCDs for continuity of care; and follow individuals without NCDs but with elevated glucose, prehypertension or other risk factors every year, and those without risk factors every 2 years. We will monitor participants in the community to reduce attrition and to track all-cause and disease-specific mortality.

Discussion

Understanding the community burden of NCDs in resource-limited setting and testing effectiveness of community-based screening and management of NCDs will provide insights to develop national policy to address NCD burden in LMIC like Nepal.
Ulcerated Keloid Secondary to a Coexisting Complicated Epidermal Inclusion Cyst: A Sonographic Diagnosis
Authors: Pérez-Wilson Jaime , Whittle Carolina , García Viviana , Norris Frances , Castro Alex , Hitschfeld Mario
Published: April 2020

Keloid is a benign fibroblastic tumor that is most often secondary to tissue injury. The clinical presentation is a hard red or purple tumor, mostly itchy or painful. The clinical objectives are to report an ulcerated keloid secondary to a central or inner complicated epidermal inclusion cyst histologically proven and to describe the sonographic findings that permitted the diagnosis. A 29-year-old man with multiple large keloids on the chest wall presented with a two-day pain history, increased volume, and ulceration on one side. Physical examination showed a keloid with edema, peripheral erythema, and a 1-cm central ulcer with purulent discharge. On the sonogram, multiple solid dermal hypodermal pseudotumors were visualized. The lesions were well-defined hypoechogenic heterogeneous solid masses that were hypovascular with color Doppler, concordant with keloids. Within the ulcerated enlarged mass, a complicated epidermal inclusion cyst was discovered with inflammatory changes. The significance of this case lies in the very low frequency of ulceration of a keloid and the high diagnostic value of sonography to demonstrate the presence of a coexisting epidermal inclusion cyst. In the differential diagnosis of an ulcerated keloid, sonography can assist in achieving a better presurgical approach.
Cognitive aging in migraine sufferers is associated with more subjective complaints but similar age-related decline: a 5-year longitudinal study
Authors: Martins Isabel Pavão , Maruta Carolina , Alves Pedro Nacimento , Loureiro Clara , Morgado Joana , Tavares Joana , Gil-Gouveia Raquel
Published: April 2020

Objectives and background

The effect of headache on cognitive performance is controversial, due to conflicting results obtained from studies in clinical or population settings. We aimed to understand if migraine and other headaches modify the rates of decline on different cognitive measures, during a 5-year interval.

Design and method

A cohort of community dwelling adults (> 50 years) with migraine (MH), non-migraine headaches (NMH) and controls without headache (WoH), was assessed by a comprehensive neuropsychological battery with tests of memory, language and executive functions, repeated 5 years apart. Change in performance between baseline and reevaluation was compared between groups, and controlled for age, gender, literacy and depressive symptoms.

Results

A total of 275 participants (78.5% WoH, 12.7% MH, 8.7% NMH) were reevaluated (average age 70.40 + 8.34 years, 64% females). Cognitive decline or dementia occurred in 11.4%, with a similar proportion among the three groups. Although MH participants had significantly more subjective cognitive complaints (p = 0.030, 95%CI:]-3.929,-0.014[), both MH and NMH subjects showed an age-associated decline identical to controls. Furthermore, migraine features (disease and attack duration, frequency and aura) were unrelated with cognitive performance.

Conclusion

Migraine and non-migraine headache are not associated with increasing risk of dementia or cognitive decline at an older age although subjects with migraine have more cognitive complaints. Longer longitudinal studies are necessary to understand if this pattern persists for more than 5 years.
A Comparative Study on the Ferroelectric Performances in Atomic Layer Deposited Hf0.5Zr0.5O2 Thin Films Using Tetrakis(ethylmethylamino) and Tetrakis(dimethylamino) Precursors
Authors: Kim Baek Su , Hyun Seung Dam , Moon Taehwan , Do Kim Keum , Lee Young Hwan , Park Hyeon Woo , Lee Yong Bin , Roh Jangho , Kim Beom Yong , Kim Ho Hyun , Park Min Hyuk , Hwang Cheol Seong
Published: April 2020

The chemical, physical, and electrical properties of the atomic layer deposited Hf0.5Zr0.5O2 thin films using tetrakis(ethylmethylamino) (TEMA) and tetrakis(dimethylamino) (TDMA) precursors are compared. The ligand of the metal-organic precursors strongly affects the residual C concentration, grain size, and the resulting ferroelectric properties. Depositing Hf0.5Zr0.5O2 films with the TDMA precursors results in lower C concentration and slightly larger grain size. These findings are beneficial to grow more ferroelectric-phase-dominant film, which mitigates its wake-up effect. From the wake-up test of the TDMA-Hf0.5Zr0.5O2 film with a 2.8 MV/cm cycling field, the adverse wake-up effect was well suppressed up to 105 cycles, with a reasonably high double remanent polarization value of ~40 μC/cm2. The film also showed reliable switching up to 109 cycles with the 2.5 MV/cm cycling field without involving the wake-up effect but with the typical fatigue behavior.
Curcumin-Loaded Nanoparticles with Low-Intensity Focused Ultrasound-Induced Phase Transformation as Tumor-Targeted and pH-Sensitive Theranostic Nanoplatform of Ovarian Cancer
Authors: Guo Xiaoxia , Mei Jie , Jing Yong , Wang Shiguang
Published: April 2020

We have developed a simple and versatile nanoplatform using pH-sensitive ferritin nanocages co-loaded with the anticancer drug curcumin (Cur) and liquid fluorocarbon perfluorohexane (PFH) inside the core and conjugated tumor-targeting molecule FA outside the shell referred to as FA-FCP. The synthesized FA-FCP has an average particle diameter of 47 nm, with stable and favorable physicochemical properties in different media, and high biocompatibility and biosafety in vivo and in vitro. Under the conditions of low-intensity focused ultrasound (LIFU) and at pH = 5.0, FA-FCP released a large amount of drugs (53.2%) in 24 h. After 4 min of LIFU (7 W) treatment, FA-FCP provided contrast-enhanced ultrasound imaging capabilities at pH = 5.0. Due to FA receptor-mediated endocytosis, FA-FCP could efficiently enter the cells and further relocate to lysosomes. Eighteen hours after injection of FA-FCP, the tumor was stimulated by LIFU, resulting in a contrast-enhanced ultrasound image. In vivo and in vitro experiments showed that the combined use of FA-FCP and LIFU had significant tumor treatment effects. Based on the results, it was concluded that FA-FCP combined with the external LIFU and the endogenic acidic environment can have powerful theranostic functions and provide a novel type of non-invasive and integrated tumor theranostic option.
Synergistic Delamination Toughening of Glass Fiber-Aluminum Laminates by Surface Treatment and Graphene Oxide Interleaf
Authors: Wu Xiaopeng , Ning Huiming , Liu Yaolu , Hu Ning , Liu Feng , Wang Shu , Huang Kaiyan , Jiao Yudu , Weng Shayuan , Liu Qiang , Wu Liangke
Published: April 2020

The synergistic effects of surface treatment and interleaf on the interlaminar mechanical properties of glass fiber-aluminum laminates were studied. Aluminum sheets were treated with alkaline etching. Meanwhile, a graphene oxide (GO) interleaf was introduced between the aluminum sheet and the glass fiber-reinforced epoxy composite. Double cantilever beam and end-notched flexure tests were employed to evaluate the interlaminar fracture toughness of the glass fiber-aluminum laminates. The obtained results show that the toughening efficiency of the interleaf is dependent on the aluminum surface characteristics as well as the GO loading. Further comparison reveals that the highest mode-I and mode-II fracture toughnesses are obtained in the specimens with alkali etching treatment and addition of GO interleaf with 0.5 wt% of GO loading, which are 510% and 381% higher in comparison to the plain specimen. Fracture surfaces were observed to further uncover the reinforcement mechanisms.
The toxicity of lithium to human cardiomyocytes
Authors: Shen Junwei , Li Xin , Shi Xiujuan , Wang Wei , Zhou Hua , Wu Jiawen , Wang Xin , Li Jue
Published: April 2020

Background

Lithium is widely used in the electronic consumer market and electric vehicles and has a great contribution to the world economy, resulting in large quantities of lithium waste in the environment. The Yangtze River Basin is one of the most developed areas in China. However, the environmental influence of lithium in the Yangtze River Basin and its roles in cardiomyocytes have not yet been clarified.

Results

Here, we found that the concentration of lithium in the water environment is very high in Shanghai, as well as in tap water, which might be caused by the pollution of lithium batteries. Lithium inhibits cell viability and proliferation of human cardiomyocytes. Moreover, lithium promotes cell apoptosis significantly. And we found that lithium controls cardiomyocytes’ functions through regulating glycogen synthase kinase 3 beta signaling.

Conclusions

This study reveals that the water environment of Shanghai might be polluted by the lithium batteries; and the enrichment of lithium might cause damage to human cardiomyocytes. It is imperative to detect lithium concentration in the water environments (such as tap water and irrigation water) and effectively recycle lithium batteries in the future.
General trends in freshwater ecological restoration practice in China over the past two decades: the driving factors and the evaluation of restoration outcome
Authors: Wu Juan , Dai Yanran , Cheng Shuiping
Published: April 2020

Background

Although freshwater ecological restoration (FER) has undergone an immense development over the past two decades in China either in the number of projects or in the spatial scale of implementations, a dearth of clear and comprehensive trends in this field is still a particular concern. We conducted a literature survey through searching the database of Web of Science between 1997 and 2017 to investigate the driving force behind FER practice and to summarize the restoration outcomes.

Results

A total of 2047 publications were hit and 198 of them were finally retained after manual screening. The number of studies in this field has been steadily increasing in recent years and their provincial distribution is positively correlated with GDP growth and the investment to pollution control and environmental protection, suggesting that economic development is a key driving factor of FER practice. Among the remaining articles, nearly half (46.5%) focus on lake ecosystems, and 34.8% and 32.8% of the studies indicate that land reclamation and eutrophication are the predominant causes of freshwater ecosystem degradation. The overarching target of the restoration is biodiversity increase (31.4%), followed by water quality improvement (24.7%) and ecosystem services (23.9%). Revegetation is a dominant restoration approach (40.9%). Reference sites for assessment of restoration projects are normally control locations without intervention (60%), or the status of the targeted sites before the interventions. For the restoration outcome evaluation, 86% of the studies present positive outcomes in terms of water quality improvement, and 79% have improvement in biological features. The most frequently monitored organisms are macrophytes (31%), followed by benthos as indicators of ecological condition.

Conclusions

Economic growth, water pollution and investment into environmental protection are the main driving factors of FER practice in China. The effort of restoration and evaluation over the past two decades has not been limited to improving hydrological function and water quality, but also pay increasingly more attention to biological processes and ecological integrity, and further the ecosystem services in recent years. However, the lack of long-term monitoring and socioeconomic attributes considered in restoration success assessments are still particular issues that need to be addressed in the future FER researches and projects.
Distinguishing pleiotropy from linked QTL between milk production traits and mastitis resistance in Nordic Holstein cattle
Authors: Cai Zexi , Dusza Magdalena , Guldbrandtsen Bernt , Lund Mogens Sandø , Sahana Goutam
Published: April 2020

Background

Production and health traits are central in cattle breeding. Advances in next-generation sequencing technologies and genotype imputation have increased the resolution of gene mapping based on genome-wide association studies (GWAS). Thus, numerous candidate genes that affect milk yield, milk composition, and mastitis resistance in dairy cattle are reported in the literature. Effect-bearing variants often affect multiple traits. Because the detection of overlapping quantitative trait loci (QTL) regions from single-trait GWAS is too inaccurate and subjective, multi-trait analysis is a better approach to detect pleiotropic effects of variants in candidate genes. However, large sample sizes are required to achieve sufficient power. Multi-trait meta-analysis is one approach to deal with this problem. Thus, we performed two multi-trait meta-analyses, one for three milk production traits (milk yield, protein yield and fat yield), and one for milk yield and mastitis resistance.

Results

For highly correlated traits, the power to detect pleiotropy was increased by multi-trait meta-analysis compared with the subjective assessment of overlapping of single-trait QTL confidence intervals. Pleiotropic effects of lead single nucleotide polymorphisms (SNPs) that were detected from the multi-trait meta-analysis were confirmed by bivariate association analysis. The previously reported pleiotropic effects of variants within theDGAT1andMGST1genes on three milk production traits, and pleiotropic effects of variants inGHRon milk yield and fat yield were confirmed. Furthermore, our results suggested that variants inKCTD16,KCNK18andENSBTAG00000023629had pleiotropic effects on milk production traits. For milk yield and mastitis resistance, we identified possible pleiotropic effects of variants in two genes,GCandDGAT1.

Conclusions

Multi-trait meta-analysis improves our ability to detect pleiotropic interactions between milk production traits and identifies variants with pleiotropic effects on milk production traits and mastitis resistance. In particular, this should contribute to better understand the biological mechanisms that underlie the unfavorable genetic correlation between milk yield and mastitis.
Gut microbiota in children with juvenile idiopathic arthritis: characteristics, biomarker identification, and usefulness in clinical prediction
Authors: Qian Xubo , Liu Yong-Xin , Ye Xiaohong , Zheng Wenjie , Lv Shaoxia , Mo Miaojun , Lin Jinjing , Wang Wenqin , Wang Weihan , Zhang Xianning , Lu Meiping
Published: April 2020

Background

Recent studies have suggested that the gut microbiota is altered in children with juvenile idiopathic arthritis (JIA). However, age, sex, and body mass index (BMI) were not matched in the previous studies, and the results are inconsistent. We conducted an age-, sex-, and BMI-matched cross-sectional study to characterize the gut microbiota in children with JIA, and evaluate its potential in clinical prediction.

Methods

A total of 40 patients with JIA and 42 healthy controls, ranging from 1 to 16 years, were enrolled in this study. Fecal samples were collected for 16S rDNA sequencing. The data were analyzed using QIIME software and R packages. Specifically, the random forest model was used to identify biomarkers, and the receiver operating characteristic curve and the decision curve analysis were used to evaluate model performance.

Results

A total of 39 fecal samples from patients with JIA, and 42 fecal samples from healthy controls were sequenced successfully. The Chao 1 and Shannon–Wiener index in the JIA group were significantly lower than those in the control group, and the Bray-Curtis dissimilarity also differed significantly between the two groups. The relative abundance of 4 genera, Anaerostipes, Dialister, Lachnospira, and Roseburia, decreased significantly in the JIA group compared to those in the control group. The 4 genera included microbes that produce short-chain fatty acids (SCFAs) and were negatively correlated with some rheumatic indices. Moreover, 12 genera were identified as potential biomarkers by using the nested cross-validation function of the random forest. A random forest model constructed using these genera was able to differentiate the patients with JIA from the healthy controls, and the area under the receiver operating characteristic curve was 0.7975. The decision curve analysis indicated that the model had usefulness in clinical practice.

Conclusions

The gut microbiota in patients with JIA is altered and characterized by a decreased abundance of 4 SCFA-producing genera. The decreases in the 4 genera correlated with more serious clinical indices. Twelve genera could be used as biomarkers and predictors in clinical practice.

Trial registration

The study is registered online at the Chinese Clinical Trial Registry on 11 May 2018 (registration number: ChiCTR1800016110).
The barley stripe mosaic virus expression system reveals the wheat C2H2 zinc finger protein TaZFP1B as a key regulator of drought tolerance
Authors: Cheuk Arnaud , Ouellet Francois , Houde Mario
Published: April 2020

Background

Drought stress is one of the major factors limiting wheat production globally. Improving drought tolerance is important for agriculture sustainability. Although various morphological, physiological and biochemical responses associated with drought tolerance have been documented, the molecular mechanisms and regulatory genes that are needed to improve drought tolerance in crops require further investigation. We have used a novel 4-component version (for overexpression) and a 3-component version (for underexpression) of a barley stripe mosaic virus-based (BSMV) system for functional characterization of the C2H2-type zinc finger protein TaZFP1B in wheat. These expression systems avoid the need to produce transgenic plant lines and greatly speed up functional gene characterization.

Results

We show that overexpression of TaZFP1B stimulates plant growth and up-regulates different oxidative stress-responsive genes under well-watered conditions. Plants that overexpress TaZFP1B are more drought tolerant at critical periods of the plant’s life cycle. Furthermore, RNA-Seq analysis revealed that plants overexpressing TaZFP1B reprogram their transcriptome, resulting in physiological and physical modifications that help wheat to grow and survive under drought stress. In contrast, plants transformed to underexpress TaZFP1B are significantly less tolerant to drought and growth is negatively affected.

Conclusions

This study clearly shows that the two versions of the BSMV system can be used for fast and efficient functional characterization of genes in crops. The extent of transcriptome reprogramming in plants that overexpress TaZFP1B indicates that the encoded transcription factor is a key regulator of drought tolerance in wheat.
Internal ammonium excess induces ROS-mediated reactions and causes carbon scarcity in rice
Authors: Yang Shunying , Hao Dongli , Jin Man , Li Yi , Liu Zengtai , Huang Yanan , Chen Tianxiang , Su Yanhua
Published: April 2020

Background

Overuse of nitrogen fertilizers is often a major practice to ensure sufficient nitrogen demand of high–yielding rice, leading to persistent NH4+ excess in the plant. However, this excessive portion of nitrogen nutrient does not correspond to further increase in grain yields. For finding out the main constraints related to this phenomenon, the performance of NH4+ excess in rice plant needs to be clearly addressed beyond the well-defined root growth adjustment. The present work isolates an acute NH4+ excess condition in rice plant from causing any measurable growth change and analyses the initial performance of such internal NH4+ excess.

Results

We demonstrate that the acute internal NH4+ excess in rice plant accompanies readily with a burst of reactive oxygen species (ROS) and initiates the downstream reactions. At the headstream of carbon production, photon caption genes and the activity of primary CO2 fixation enzymes (Rubisco) are evidently suppressed, indicating a reduction in photosynthetic carbon income. Next, the vigorous induction of glutathione transferase (GST) genes and enzyme activities along with the rise of glutathione (GSH) production suggest the activation of GSH cycling for ROS cleavage. Third, as indicated by strong induction of glycolysis / glycogen breakdown related genes in shoots, carbohydrate metabolisms are redirected to enhance the production of energy and carbon skeletons for the cost of ROS scavenging. As the result of the development of these defensive reactions, a carbon scarcity would accumulatively occur and lead to a growth inhibition. Finally, a sucrose feeding cancels the ROS burst, restores the activity of Rubisco and alleviates the demand for the activation of GSH cycling.

Conclusion

Our results demonstrate that acute NH4+ excess accompanies with a spontaneous ROS burst and causes carbon scarcity in rice plant. Therefore, under overuse of N fertilizers carbon scarcity is probably a major constraint in rice plant that limits the performance of nitrogen.
Case report: postpartum cerebral venous thrombosis misdiagnosed as postdural puncture headache
Authors: Oh Mi K. , Ryu Jae H. , Jeon Woo J. , Lee Chang W. , Cho Sang Y.
Published: April 2020

Background

Cerebral venous thrombosis can be a fatal complication of the postpartum period. Pregnancy is known to be a risk factor for thromboembolism in itself.

Case presentation

A normal spontaneous vaginal delivery was planned for a 20-year-old primigravida patient with patient-controlled epidural analgesia. Next morning, the patient complained of an occipital headache. An epidural blood patch was performed for diagnostic and therapeutic purpose with 10 ml of autologous blood. That night, she had an episode of seizures. Endotracheal intubation was done to secure the airway. She was transferred to an intensive care unit. Brain CT angiography and MRI showed superior sagittal sinus thrombosis with acute infarct and mild subarachnoid haemorrhage. For cerebral venous thrombosis treatment, heparin was injected and for intracranial pressure control, a hypertonic solution was injected. Despite this medical treatment, intracranial pressure continued to rise. The next day, her mental state changed to stupor. Emergency decompressive craniectomy was performed. Her mental state improved rapidly after surgery. A week later, she was transferred to a general ward. Her health recovered and she was discharged.

Conclusions

We experienced postpartum cerebral venous thrombosis misdiagnosed as postdural puncture headache. We hope that this case report would be helpful in situation which a postpartum young woman complains severe headache in spite of management for headache including autologous epidural blood patch.
Anxiety and depression in patients who undergo a cerebrovascular procedure
Authors: Lombardo Lauren , Shaw Richard , Sayles Kathleen , Altschul Dorothea
Published: April 2020

Background

Observe the relationship of anxiety and depression on quality of life outcomes after open and endovascular cerebrovascular procedures.

Methods

We retrospectively analyzed 349 patients who underwent a procedure for aneurysm, arteriovenous malformation, intraparenchymal hemorrhage, carotid stenosis, acute stroke, and conventional catheter angiogram over three years at a community hospital. We correlated pre-procedural anxiety and depression with Global Physical Health, Global Mental Health, and Modified Rankin Scale scores. We performed univariate and multivariate linear and logistic regression analyses adjusting for past medical history and sociodemographic factors.

Results

Anxiety or depression occurred in 18 % of patients. Patients with anxiety or depression were more likely to be female (81% vs 60.8%; p = 0.002) and younger (54 vs. 59 years old; p = 0.025). The groups did not differ in type or urgency of procedure, smoking or history of diabetes. Patients with anxiety or depression reported lower mental health scores at 30 days (45.1 vs 48.2; p = 0.002) post-procedure. In multivariate analyses, anxious or depressed patients had worse mental health scores at 30 days (t = − 2.893; p = 0.008) than those who did not have a history of anxiety or depression. There was no difference between groups in length of stay, mortality, physical health t-scores, functionality scores, or six month quality of life outcomes.

Conclusions

Patients undergoing cerebrovascular procedures who self-reported anxiety or depression showed a significant difference in mental health outcomes at 30 days, but six month mental health and other medical and functional outcomes measures were similar to patients without these diagnoses.
Comprehensive routine diagnostic screening to identify predictive mutations, gene amplifications, and microsatellite instability in FFPE tumor material
Authors: Steeghs Elisabeth M. P. , Kroeze Leonie I. , Tops Bastiaan B. J. , van Kempen Leon C. , ter Elst Arja , Kastner-van Raaij Annemiek W. M. , Hendriks-Cornelissen Sandra J. B. , Hermsen Mandy J. W. , Jansen Erik A. M. , Nederlof Petra M. , Schuuring Ed , Ligtenberg Marjolijn J. L. , Eijkelenboom Astrid
Published: April 2020

Background

Sensitive and reliable molecular diagnostics is needed to guide therapeutic decisions for cancer patients. Although less material becomes available for testing, genetic markers are rapidly expanding. Simultaneous detection of predictive markers, including mutations, gene amplifications and MSI, will save valuable material, time and costs.

Methods

Using a single-molecule molecular inversion probe (smMIP)-based targeted next-generation sequencing (NGS) approach, we developed an NGS panel allowing detection of predictive mutations in 33 genes, gene amplifications of 13 genes and microsatellite instability (MSI) by the evaluation of 55 microsatellite markers. The panel was designed to target all clinically relevant single and multiple nucleotide mutations in routinely available lung cancer, colorectal cancer, melanoma, and gastro-intestinal stromal tumor samples, but is useful for a broader set of tumor types.

Results

The smMIP-based NGS panel was successfully validated and cut-off values were established for reliable gene amplification analysis (i.e. relative coverage ≥3) and MSI detection (≥30% unstable loci). After validation, 728 routine diagnostic tumor samples including a broad range of tumor types were sequenced with sufficient sensitivity (2.4% drop-out), including samples with low DNA input (< 10 ng; 88% successful), low tumor purity (5–10%; 77% successful), and cytological material (90% successful). 75% of these tumor samples showed ≥1 (likely) pathogenic mutation, including targetable mutations (e.g. EGFR, BRAF, MET, ERBB2, KIT, PDGFRA). Amplifications were observed in 5.5% of the samples, comprising clinically relevant amplifications (e.g. MET, ERBB2, FGFR1). 1.5% of the tumor samples were classified as MSI-high, including both MSI-prone and non-MSI-prone tumors.

Conclusions

We developed a comprehensive workflow for predictive analysis of diagnostic tumor samples. The smMIP-based NGS analysis was shown suitable for limited amounts of histological and cytological material. As smMIP technology allows easy adaptation of panels, this approach can comply with the rapidly expanding molecular markers.
Impact of alcohol marketing on drinkers with Alcohol use disorders seeking treatment: a mixed-method study protocol
Authors: Guillou-Landreat Morgane , Dany Antoine , Le Reste Jean Yves , Le Goff Delphine , Benyamina Amine , Grall-Bronnec Marie , Gallopel-Morvan Karine
Published: April 2020

Background

The marketing of alcohol influences patterns of alcohol consumption. Existing studies have focused, for the most part, on adolescents and the links between exposure to marketing and alcohol initiation. In France, the Evin law, a French exception, was set up in 1991 with the aim of regulating this exposure to marketing, but since 2009 it has been severely compromised. Alcohol consumption causes severe damage, which may be seenfrom 1 standard unit per day and mostly among adults who are regular users of alcohol. In this at-risk population, studies analysing the impact of marketing are sparse.

The specific objectives include (i) the evaluation of the perception of alcohol marketing by patients with an AUD (ii) gaining understanding of the links between alcohol marketing and patients with AUD behaviours (iii) the development of alcohol demarketing strategy in patients receiving AUD coaching.

Methods

Our main objective isto evaluate the impact of marketing on a population with an AUD. The methodology was in 4 steps: step 1 is a pre-test (N = 100) selecting type of alcohol consumed and type of marketing stimuli identified by patients aged 18 + with an AUD. Step 2 is a qualitative study (N = 20), with in-depth interview, to understand links between alcohol marketing and patients with AUD behaviours. Step 3 is a quantitative study(N = 600) to confirm these links and the impact of alcohol marketing on patients with AUD behaviours. Step 4 is an interventional step, including and testing the impact of demarketing intervention on patients with AUD while using the results of the three first steps (N = 120).

Discussion

This study will contribute to a better definition of the impact of alcohol marketing on patients with AUD and will enable identification of the determinants of this impact. These data will inform the development of interventions that take into account demarketingstrategies on patients under AUD management.

Trial registration

The Trial registrationregistration number is NCT03876132, and it was registered on the 15th march 2019.
The use of a synthetic shoulder patch for large and massive rotator cuff tears – a feasibility study
Authors: Cowling P. , Hackney R. , Dube B. , Grainger A. J. , Biglands J. D. , Stanley M. , Song D. , Conaghan P. G. , Kingsbury S. R.
Published: April 2020

Background

The aim of this study was to explore the feasibility of using a non-absorbable biocompatible polyester patch to augment open repair of massive rotator cuff tears (Patch group) and compare outcomes with other treatment options (Non-patch group).

Methods

Participants referred to orthopaedic clinics for rotator cuff surgery were recruited. Choice of intervention (Patch or Non-patch) was based on patient preference and intra-operative findings. Oxford Shoulder Score (OSS), Shoulder Pain and Disability Index (SPADI), and Constant score were completed at baseline and 6 months. Shoulder MRI was performed at baseline and 6 months to assess fat fraction and Goutallier classification pre- and post- treatment. Feasibility outcomes (including retention, consent and missing data) were assessed.

Results

Sixty-eight participants (29 in the Patch group, 39 in Non-patch group) were included (mean age 65.3 years). Conversion to consent (92.6%), missing data (0% at baseline), and attrition rate (16%) were deemed successful feasibility endpoints. There was significant improvement in the Patch group compared to Non-patch at 6 months in OSS (difference in medians 9.76 (95% CI 2.25, 17.29) and SPADI: 22.97 (95% CI 3.02, 42.92), with no substantive differences in Constant score. The patch group had a higher proportion of participants improving greater than MCID for OSS (78% vs 62%) and SPADI (63% vs 50%) respectively. Analysis of the 48 paired MRIs demonstrated a slight increase in the fat fraction for supraspinatus (53 to 55%), and infraspinatus (26 to 29%) at 6 months. These differences were similar and in the same direction when the participants were analysed by treatment group. The Goutallier score remained the same or worsened one grade in both groups equally.

Conclusions

This study indicates that a definitive clinical trial investigating the use of a non-absorbable patch to augment repair of massive rotator cuff tears is feasible. In such patients, the patch has the potential to improve shoulder symptoms at 6 months.

Trial registration

ISRCTN, ISRCTN79844053, Registered 15th October 2014 (retrospectively registered).
Influence of cavity depth and restoration of non-carious cervical root lesions on strain distribution from various loading sites
Authors: Du Je-Kang , Wu Ju-Hui , Chen Ping-Ho , Ho Pei-Shan , Chen Ker-Kong
Published: April 2020

Background

We aimed to investigate the load-induced strain variation in teeth with unrestored and resin-based composite restored non-carious cervical lesions (NCCLs).

Methods

Twelve extracted premolars were provided for measuring buccal-side root NCCLs. Strain gauges were fixed at four measuring sites of each tooth, two at the buccal surface and two at the lingual surface. NCCLs were prepared with occlusal margins at the cemento-enamel junction. A static 9-kg load was applied at seven occlusal loading points: buccal cusp tip (BC), inner inclination of the BC, lingual cusp tip (LC), inner inclination of the LC, center of the mesial marginal ridge or distal marginal ridge, and center of the central groove. The strain was detected at each site in teeth with NCCL depths of 0 (control), 0.5, 1.0, and 1.5 mm. Each NCCL was restored using an adhesive composite resin, and the strains were re-measured.

Results

The strains at the NCCL occlusal and gingival margins decreased with increasing defect depths, and the effect was significant when the depth of the defect was 1.5 mm. Loading on the buccal and lingual cusps induced prominent strain variation. The strains at all depth distribution recovered to nearly intact conditions when the NCCLs were restored.

Conclusions

NCCLs at 1.5 mm depth are detrimental, but they can be restored using resin composites.

Clinical significance

The existence of NCCLs should not be ignored. The depth of the NCCL may affect the progression of the lesion. Resin composite restoration is an appropriate method for preventing persistent NCCL deterioration.
Mapping clinical reasoning literature across the health professions: a scoping review
Authors: Young Meredith E. , Thomas Aliki , Lubarsky Stuart , Gordon David , Gruppen Larry D. , Rencic Joseph , Ballard Tiffany , Holmboe Eric , Da Silva Ana , Ratcliffe Temple , Schuwirth Lambert , Dory Valérie , Durning Steven J.
Published: April 2020

Background

Clinical reasoning is at the core of health professionals’ practice. A mapping of what constitutes clinical reasoning could support the teaching, development, and assessment of clinical reasoning across the health professions.

Methods

We conducted a scoping study to map the literature on clinical reasoning across health professions literature in the context of a larger Best Evidence Medical Education (BEME) review on clinical reasoning assessment. Seven databases were searched using subheadings and terms relating to clinical reasoning, assessment, and Health Professions. Data analysis focused on a comprehensive analysis of bibliometric characteristics and the use of varied terminology to refer to clinical reasoning.

Results

Literature identified: 625 papers spanning 47 years (1968–2014), in 155 journals, from 544 first authors, across eighteen Health Professions. Thirty-seven percent of papers used the term clinical reasoning; and 110 other terms referring to the concept of clinical reasoning were identified. Consensus on the categorization of terms was reached for 65 terms across six different categories: reasoning skills, reasoning performance, reasoning process, outcome of reasoning, context of reasoning, and purpose/goal of reasoning. Categories of terminology used differed across Health Professions and publication types.

Discussion

Many diverse terms were present and were used differently across literature contexts. These terms likely reflect different operationalisations, or conceptualizations, of clinical reasoning as well as the complex, multi-dimensional nature of this concept. We advise authors to make the intended meaning of ‘clinical reasoning’ and associated terms in their work explicit in order to facilitate teaching, assessment, and research communication.
Colorectal Cancer (CRC) treatment and associated costs in the public sector compared to the private sector in Johannesburg, South Africa
Authors: Herbst Candice-lee , Miot Jacqueline K. , Moch Shirra L. , Ruff Paul
Published: April 2020

Background

South Africa’s divided healthcare system is believed to be inequitable as the population serviced by each sector and the treatment received differs while annual healthcare expenditure is similar. The appropriateness of treatment received and in particular the cost of the same treatment between the sectors remains debatable and raises concerns around equitable healthcare. Colorectal cancer places considerable pressure on the funders, yet treatment utilization data and the associated costs of non-communicable diseases, in particular colorectal cancer, are limited for South Africa. Resources need to be appropriately managed while ensuring equitable healthcare is provided regardless of where the patient is able to receive their treatment. Therefore the aim of this study was to determine the cost of colorectal cancer treatment in a privately insured patient population in order to compare the costs and utilization to a previously published public sector patient cohort.

Methods

Private sector costs were determined using de-identified claim-based data for all newly diagnosed CRC patients between 2012 and 2014. The costs obtained from this patient cohort were compared to previously published public sector data for the same period. The costs compared were costs incurred by the relevant sector funder and didn’t include out-of-pocket costs.

Results

The comparison shows private sector patients gain access to more of the approved regimens (12 vs. 4) but the same regimens are more costly, for example CAPOX costs approximately €150 more per cycle. The cost difference between 5FU and capecitabine monotherapy is less than €30 per cycle however, irinotecan is cheaper in comparison to oxaliplatin in the private sector (FOLFOX approx. €500 vs. FOLFIRI aprox. €460). Administrative costs account for up to 45% of total costs compared to the previously published data of these costs totaling < 15% of the full treatment cost in South Africa’s public healthcare system.

Conclusion

This comparison highlights the disparities between sectors while illustrating the need for further research to improve resource management to attain equitable healthcare.
CREB1-induced miR-1204 promoted malignant phenotype of glioblastoma through targeting NR3C2
Authors: Zhao Xinli , Shen Fazheng , Ma Jiwei , Zhao Shupeng , Meng Lei , Wang Xiangyang , Liang Shufeng , Liang Jianing , Hu Chaoshuai , Zhang Xinzhong
Published: April 2020

Background

Glioblastoma (GBM) is a subclass of brain malignancy with unsatisfactory prognosis. MicroRNAs (miRNAs) are a group of non-coding RNAs (ncRNAs) that exert key function on tumorigenesis and tumor development.

Purposes

The purpose of this work was to unravel the biological behavior and mechanism of miR-1204 in GBM.

Methods

Expressions of miR-1204, NR3C2 and CREB1 were detected by RT-qPCR and western blot. Proliferation and apoptosis of GBM cells were detected by CCK-8, colony formation, caspase-3 activity and TUNEL assays. Molecular interplays were examined by ChIP, RIP, and luciferase reporter assays.

Results

MiR-1204 level was elevated in GBM cell lines. Functionally, miR-1204 aggravated cell proliferation whereas suppressed cell apoptosis in GBM cells. Mechanistically, cAMP Responsive Element Binding Protein 1 (CREB1) bound to the promoter of miR-1204 and activated the transcription of miR-1204. Furthermore, miR-1204 targeted and inhibited Nuclear receptor subfamily 3 group C member 2 (NR3C2), a tumor suppressor gene in GBM cells. Rescue assays indicated that NR3C2 participated in the regulation of miR-1204 on the malignant phenotype of GBM cells.

Conclusions

We observed for the first time that CREB1-induced miR-1204 promoted malignant phenotype of GBM through targeting NR3C2, indicating that miR-1204 acted as a novel oncogenic miRNA in GBM.
The predictive value of lncRNA MIR31HG expression on clinical outcomes in patients with solid malignant tumors
Authors: Tu Chao , Ren Xiaolei , He Jieyu , Li Shuangqing , Qi Lin , Duan Zhixi , Wang Wanchun , Li Zhihong
Published: April 2020

Background

Emerging studies have explored the prognostic value of MIR31HG in cancers, but its role remains elusive. Herein, we aimed to summarize the prognostic potential of MIR31HG in this study.

Methods

Several databases were searched for literature retrieval on Dec 5, 2019. Overall and subgroup analyses were conducted to measure the relationship between MIR31HG expression and clinical outcomes. Moreover, GEPIA was applied for validation of prognostic value of MIR31HG in tumor patients in TCGA dataset.

Results

Overall, seventeen studies with 2573 patients were enrolled. Compared to counterparts, those patients with high MIR31HG expression tended to have shorter RFS. Notably, MIR31HG overexpression predicted unfavorable OS in lung cancer. By contrast, gastrointestinal cancer patients with elevated MIR31HG expression predicted better OS and disease-free survival. Additionally, MIR31HG overexpression was significantly associated with worse clinicopathological features including advanced tumor stage and LNM in lung cancer, but favorable clinical characteristics in gastrointestinal cancer. Moreover, the positive association between MIR31HG and OS in lung cancer was further confirmed in TCGA dataset.

Conclusion

Overexpression of MIR31HG suggested remarkable association with poor prognosis in terms of OS, tumor stage, and LNM in lung cancer, but favorable prognosis in gastrointestinal cancer. Therefore, MIR31HG may serve as a promising prognostic biomarker in multiple cancers.
The yin and yang functions of extracellular ATP and adenosine in tumor immunity
Authors: Feng Li-li , Cai Yi-qing , Zhu Ming-chen , Xing Li-jie , Wang Xin
Published: April 2020

Extracellular adenosine triphosphate (eATP) and its main metabolite adenosine (ADO) constitute an intrinsic part of immunological network in tumor immunity. The concentrations of eATP and ADO in tumor microenvironment (TME) are controlled by ectonucleotidases, such as CD39 and CD73, the major ecto-enzymes expressed on immune cells, endothelial cells and cancer cells. Once accumulated in TME, eATP boosts antitumor immune responses, while ADO attenuates immunity against tumors. eATP and ADO, like yin and yang, represent two opposite aspects from immune-activating to immune-suppressive signals. Here we reviewed the functions of eATP and ADO in tumor immunity and attempt to block eATP hydrolysis, ADO formation and their contradictory effects in tumor models, allowing the induction of effective anti-tumor immune responses in TME. These attempts documented that therapeutic approaches targeting eATP/ADO metabolism and function may be effective methods in cancer therapy.