bluuebunny/crossref_metadata_2025_split huggingface dataset:
A panel of protein kinase high expression is associated with postoperative recurrence in cholangiocarcinoma
Authors: Padthaisong Sureerat , Thanee Malinee , Namwat Nisana , Phetcharaburanin Jutarop , Klanrit Poramate , Khuntikeo Narong , Titapun Attapol , Loilome Watcharin 
Published: February 2020

Abstract
Background
Cancer recurrence is one of the most concerning clinical problems of cholangiocarcinoma (CCA) patients after treatment. However, an identification of predictive factor on Opisthorchis viverrini (OV)-associated CCA recurrence is not well elucidated. In the present study, we aimed to investigate the correlation of twelve targeted protein kinases with CCA recurrence.

Methods
Twelve protein kinases, epidermal growth factor receptor (EGFR), human epidermal growth factor receptor 2, 3, 4 (HER2, HER3, HER4), vascular endothelial growth factor receptor 3 (VEGFR3), vascular endothelial growth factor-C (VEGF-C), erythropoietin-producing hepatocellular carcinoma receptor type-A3 (EphA3), EphrinA1, phosphor-serine/threonine kinase 1 (p-Akt1), serine/threonine kinase 1 (Akt1), beta-catenin and protein Wnt5a (Wnt5a) were examined using immunohistochemistry. Pre-operative serum tumor markers, CA19–9 and CEA were also investigated.

Results
Among twelve protein kinases, EGFR, HER4, and EphA3 were associated with tumor recurrence status, recurrence-free survival (RFS) and overall survival (OS). Multivariate cox regression demonstrated that EGFR, HER4, EphA3 or the panel of high expression of these proteins was an independent prognostic factor for tumor recurrence. The combination of high expression of these proteins with a high level of CA19–9 could improve the predictive ability on tumor recurrence. Moreover, the patients were stratified more accurately when analyzed using the combination of high expression of these proteins with primary tumor (T) or lymph node metastasis (N) status.

Conclusion
EGFR, HER4, EphA3 or the panel of high expression of these proteins is an independent prognostic factor for post-operative CCA recurrence.
Effects of the LASIK flap thickness on corneal biomechanical behavior: a finite element analysis
Authors: Fang Lihua , Wang Yan , Yang Ruizhi , Deng Sijing , Deng Jiahao , Wan Linsun 
Published: February 2020

Abstract
Background
It is well known that the biomechanical properties change after LASIK refractive surgery. One reason is the impact of flap creation on the residual stroma. The results have revealed that the change is closely related with the flap thickness in several studies. However, the quantitative relationships between the distributions of displacement and stress on the corneal surface and flap thickness have not been studied. The aim of the study was to quantify evaluate the biomechanical change caused by the LASIK flap.

Methods
By building a finite element model of the cornea, the displacement, the stress and the strain on the corneal surface were analyzed.

Results
The results showed that the corneal flap could obviously cause the deformation of the anterior corneal surface. For example, the displacement of the corneal vertex achieved 15 μm more than that without corneal flap, when the thickness of corneal flap was 120 μm thick. This displacement was enough to cause the change of aberrations in the human eyes. In the central part of the cornea, the stress on the anterior corneal surface increased with flap thickness. But the change in the stress on the posterior corneal surface was significantly less than that on the anterior surface. In addition, the stress in the central part of the anterior corneal surface increased significantly as the intra-ocular pressure (IOP) increase. Furthermore the increase of IOP had a clearly less effect on stress distribution at the edge of the cornea. Distributions of strain on the corneal surface were similar to those of stress.

Conclusions
The changes in the biomechanical properties of cornea after refractive surgery should not be ignored.
High-resolution iris and retinal imaging in multisystemic smooth muscle dysfunction syndrome due to a novel Asn117Lys substitution in ACTA2: a case report
Authors: Mc Glacken-Byrne Aisling B. , Prentice David , Roshandel Danial , Brown Michael R. , Tuch Philip , Yau Kyle S.-Y. , Sivadorai Padma , Davis Mark R. , Laing Nigel G. , Chen Fred K. 
Published: February 2020

Abstract
Background
Congenital mydriasis and retinal arteriolar tortuosity are associated with the life-threatening multisystemic smooth muscle dysfunction syndrome (MSMDS) due to mutations in the gene, ACTA2, which encodes alpha-smooth muscle actin (α-SMA). Previous reports attributed MSMDS-related congenital mydriasis to the absence of iris sphincter muscle. Similarly, it has been hypothesized that abnormal proliferation of the vascular smooth muscle cells causes the marked tortuosity of retinal arterioles in MSMDS. In this report, high-resolution ocular imaging reveals unexpected findings that reject previous hypotheses.

Case presentation
The proband is a 37-year-old female with a history of neonatal patent ductus arteriosus (PDA) ligation, left-sided choreiform movements at the age of 11 and a transient aphasia with right-sided weakness at the age of 30. Her older sister also had PDA ligation and congenital mydriasis but no neurological deficit up to age 41. Magnetic resonance angiogram demonstrated cerebrovascular lesions resembling but distinct from Moyamoya disease, characterised by internal carotid artery dilatation, terminal segment stenosis and absent basal collaterals. Their mother had poorly reactive pupils with asymptomatic cerebral arteriopathy resembling her daughters. All three had prominent retinal arteriolar tortuosity. The daughters were heterozygous and the mother was a somatic mosaic for a novel c.351C > G (p.Asn117Lys) transversion in ACTA2. Iris optical coherence tomography (OCT) showed a hyporeflective band anterior to the pigment epithelium indicating the presence of dysfunctional sphincter muscle. Adaptive optics retinal imaging showed no thickening of the arteriolar vessel wall whilst OCT angiography showed extreme corkscrew course of arterioles suggesting vessel elongation.

Conclusions
In addition to the known association between Met46, Arg179 and Arg258 substitutions and ACTA2-related arteriopathy, this case illustrates the possibility that Asn117 also plays an important role in α-SMA function within the cerebrovascular smooth muscle cell. MSMDS-related congenital mydriasis is due to reduced iris sphincter contractility rather than its absence. Retinal arteriolar tortuosity might be due to longitudinal proliferation of arteriolar smooth muscle cells. The described cerebrovascular and ocular signs are consistent with predicted effects of the novel Asn117Lys substitution in ACTA2.
Blood cell for the differentiation of airway inflammatory phenotypes in COPD exacerbations
Authors: Gao Jie , Chen Bida , Wu Sifang , Wu Feng 
Published: February 2020

Abstract
Background
Measurement of sputum is frequently used to define airway inflammatory subtypes. The venous blood cell is a reliable and simple biomarker, may be used as an alternative procedure to reflect the subtypes. For the aim of verifying the hypothesis that venous blood cell can quantify sputum inflammatory cell to access the airway subtypes in chronic obstructive pulmonary disease of acute exacerbations (AECOPD) and to ascertain the accuracy of the blood cell biomarker.

Methods
This study evaluated 287 patients with COPD exacerbations and all four tests were performed on the same day, which are lung function test, bronchodilator reversibility test, sputum cell analysis and blood routine examination.

Results
There was a correlation between sputum eosinophils and blood eosinophils, blood cells derived ratios. There was a weaker relationship to neutrophils between sputum and blood. Sputum neutrophils had not any association with neutrophil/macrophage ratio (NMR) and eosinophil/lymphocyte ratio (ELR) in blood. Blood eosinophils percentage was predictive for eosinophilic COPD exacerbations with an area under the curve (AUC) of 0.672 (p = 0.012). The optimum cutpoint for blood eosinophils percentage was 0.55%. Blood eosinophils absolute count was also predictive sputum eosinophilia at 0.35 × 109/L (AUC = 0.626, p = 0.025). ELR, eosinophil/monocyte ratio (EMR) and eosinophil/neutrophil ratio (ENR) in blood were higher in COPD exacerbations with mixed granulocytic and eosinophilic subtypes.

Conclusion
Eosinophils/neutrophils count parameters were relationship between blood and sputum. Eosinophils in blood and the ratios (ENR, EMR and ELR) may be utilized to assess eosinophilic airway inflammation in COPD exacerbations. Due to weak relationship and poor predictive ability, more researches should be required.
PrEvention of posttraumatic contractuRes with Ketotifen 2 (PERK 2) – protocol for a multicenter randomized clinical trial
Authors: Ademola Ayoola , Hildebrand Kevin A. , Schneider Prism S. , Mohtadi Nicholas G. H. , White Neil J. , Bosse Michael J. , Garven Alexandra , Walker Richard E. A. , Sajobi Tolulope T. 
Published: February 2020

Abstract
Background
Injuries and resulting stiffness around joints, especially the elbow, have huge psychological effects by reducing quality of life through interference with normal daily activities such as feeding, dressing, grooming, and reaching for objects. Over the last several years and through numerous research results, the myofibroblast-mast cell-neuropeptide axis of fibrosis had been implicated in post-traumatic joint contractures. Pre-clinical models and a pilot randomized clinical trial (RCT) demonstrated the feasibility and safety of using Ketotifen Fumarate (KF), a mast cell stabilizer to prevent elbow joint contractures. This study aims to evaluate the efficacy of KF in reducing joint contracture severity in adult participants with operately treated elbow fractures and/or dislocations.

Methods/design
A Phase III randomized, controlled, double-blinded multicentre trial with 3 parallel groups (KF 2 mg or 5 mg or lactose placebo twice daily orally for 6 weeks). The study population consist of adults who are at least 18 years old and within 7 days of injury. The types of injuries are distal humerus (AO/OTA type 13) and/or proximal ulna and/or proximal radius fractures (AO/OTA type 2 U1 and/or 2R1) and/or elbow dislocations (open fractures with or without nerve injury may be included). A stratified randomization scheme by hospital site will be used to assign eligible participants to the groups in a 1:1:1 ratio. The primary outcome is change in elbow flexion-extension range of motion (ROM) arc from baseline to 12 weeks post-randomization. The secondary outcomes are changes in ROM from baseline to 6, 24 & 52 weeks, PROMs at 2, 6, 12, 24 & 52 weeks and impact of KF on safety including serious adverse events and fracture healing. Descriptive analysis for all outcomes will be reported and ANCOVA be used to evaluate the efficacy KF over lactose placebo with respect to the improvement in ROM.

Discussion
The results of this study will provide evidence for the use of KF in reducing post-traumatic joint contractures and improving quality of life after joint injuries.

Trial registration
This study was prospectively registered (July 10, 2018) with ClinicalTrials.gov reference: NCT03582176.
Integration, abundance, and transmission of mutations and transgenes in a series of CRISPR/Cas9 soybean lines
Authors: Michno Jean-Michel , Virdi Kamaldeep , Stec Adrian O. , Liu Junqi , Wang Xiaobo , Xiong Yer , Stupar Robert M. 
Published: February 2020

AbstractBackgroundAs with many plant species, current genome editing strategies in soybean are initiated by stably transforming a gene that encodes an engineered nuclease into the genome. Expression of the transgene results in a double-stranded break and repair at the targeted locus, oftentimes resulting in mutation(s) at the intended site. As soybean is a self-pollinating species with 20 chromosome pairs, the transgene(s) in the T0 plant are generally expected to be unlinked to the targeted mutation(s), and the transgene(s)/mutation(s) should independently assort into the T1 generation, resulting in Mendellian combinations of transgene presence/absence and allelic states within the segregating family. This prediction, however, is not always consistent with observed results.ResultsIn this study, we investigated inheritance patterns among three different CRISPR/Cas9 transgenes and their respective induced mutations in segregating soybean families. Next-generation resequencing of four T0 plants and four T1 progeny plants, followed by broader assessments of the segregating families, revealed both expected and unexpected patterns of inheritance among the different lineages. These unexpected patterns included: (1) A family in which T0 transgenes and mutations were not transmitted to progeny; (2) A family with four unlinked transgene insertions, including two respectively located at paralogous CRISPR target break sites; (3) A family in which mutations were observed and transmitted, but without evidence of transgene integration nor transmission.ConclusionsGenome resequencing provides high-resolution of transgene integration structures and gene editing events. Segregation patterns of these events can be complicated by several potential mechanisms. This includes, but is not limited to, plant chimeras, multiple unlinked transgene integrations, editing of intended and paralogous targets, linkage between the transgene integration and target site, and transient expression of the editing reagents without transgene integration into the host genome.
The influence of cognitive schemas on the mixed anxiety-depressive symptoms of breast cancer patients
Authors: Bredicean Ana Cristina , Crăiniceanu Zorin , Oprean Cristina , Riviș Ioana Alexandra , Papavă Ion , Secoșan Ica , Frandeș Mirela , Giurgi-Oncu Cătălina , Grujic Daciana 
Published: February 2020

Abstract
Background
The surgical treatment of breast cancer involves various psychological consequences, which differ according to individual characteristics. Our study aimed to identify the role that cognitive schemas had in triggering anxiety and depressive symptoms in patients diagnosed with breast cancer that underwent oncological and plastic surgery treatment.

Methods
64 female patients, diagnosed with breast cancer from an Oncology and Plastic Surgery Hospital, were selected to participate in this study between March–June 2018. They were divided into two groups: I. 28 patients who underwent mastectomy surgery; II. 36 patients, who required mastectomy and, subsequently, also chose to undergo breast reconstruction surgery. For the purposes of evaluating a possible change in mental health status, we employed two assessment scales: the Young Cognitive Schema Questionnaire - Short Form 3 (YSQ-S3) and the Romanian version of the Depression Anxiety Stress Scale – 21 (DASS-21R).

Results
Participants who underwent mastectomy and subsequent breast reconstruction surgery employed cognitive schemas that did not generate symptoms of depression or anxiety. In contrast, the cognitive schemas found in women who refused reconstructive breast surgery were significantly correlated with the presence of anxiety-depressive symptoms. The cognitive schema domain of ‘disconnection and rejection’ correlated uncertainly with the presence of anxiety-depressive symptoms for the group with breast reconstruction (Spearman’s ρ = 0.091, p = 0.644), while for the other group the correlation was moderate-strong (Spearman’s ρ = 0.647, p <  0.01). Negative emotional schemas were significantly correlated with the presence of anxiety-depressive symptoms (Spearman’s ρ = 0.598, p <  0.01) in the group of participants without reconstructive surgery.

Conclusion
A correct identification of dysfunctional cognitive schemas and coping mechanisms at the commencement of the combined treatment in breast cancer patients could serve as an indicator for the evolution of their mental health, therefore assisting professionals in establishing the most suitable psychological, psychotherapeutic and psychiatric intervention plan.
Video-based feedback using real consultations for a formative assessment in communication skills
Authors: Dohms M. C. , Collares C. F. , Tibério I. C. 
Published: February 2020

AbstractBackgroundPre-recorded videotapes have become the standard approach when teaching clinical communication skills (CCS). Furthermore, video-based feedback (VF) has proven to be beneficial in formative assessments. However, VF in CCS with the use of pre-recorded videos from real-life settings is less commonly studied than the use of simulated patients.To explore: 1) perceptions about the potential benefits and challenges in this kind of VF; 2) differences in the CCC scores in first-year medical residents in primary care, before and after a communication program using VF in a curricular formative assessment.MethodWe conducted a pre/post study with a control group. The intervention consisted of VF sessions regarding CCS, performed in a small group with peers and a facilitator. They reviewed clinical consultations pre-recorded in a primary care setting with real patients. Before and after the intervention, 54 medical residents performed two clinical examinations with simulated patients (SP), answered quantitative scales (Perception of Patient-Centeredness and Jefferson Empathy Scale), and semi-structured qualitative questionnaires. The performances were scored by SP (Perception of Patient-Centeredness and CARE scale) and by two blind raters (SPIKES protocol-based and CCOG-based scale). The quantitative data analysis employed repeated-measures ANOVA. The qualitative analysis used the Braun and Clarke framework for thematic analysis.ResultsThe quantitative analyses did not reveal any significant differences in the sum scores of the questionnaires, except for the Jefferson Empathy Scale. In the qualitative questionnaires, the main potential benefits that emerged from the thematic analysis of the VF method were self-perception, peer-feedback, patient-centered approach, and incorporation of reflective practices. A challenging aspect that emerged from facilitators was the struggle to relate the VF with theoretical references and the resident’s initial stress to record and watch oneself on video.ConclusionVF taken from real-life settings seems to be associated with a significant increase in self-perceived empathy. The study of other quantitative outcomes related to this VF intervention needs larger sample sizes. VF with clinical patients from real healthcare settings appears to be an opportunity for a deeper level of self-assessment, peer-feedback, and reflective practices.
Member species of the Anopheles gambiae complex can be misidentified as Anopheles leesoni
Authors: Dahan-Moss Yael , Hendershot Allison , Dhoogra Minishca , Julius Henry , Zawada Jacek , Kaiser Maria , Lobo Neil F. , Brooke Basil D. , Koekemoer Lizette L. 
Published: February 2020

Abstract
Background
Accurate Anopheles species identification is key for effective malaria vector control. Identification primarily depends on morphological analysis of field samples as well as molecular species-specific identifications. During an intra-laboratory assessment (proficiency testing) of the Anopheles funestus group multiplex PCR assay, it was noted that Anopheles arabiensis can be misidentified as Anopheles leesoni, a zoophilic member of the An. funestus group. The aim of this project was, therefore, to ascertain whether other members of the Anopheles gambiae complex can also be misidentified as An. leesoni when using the standard An. funestus multiplex PCR.

Methods
The An. funestus multiplex PCR was used to amplify DNA from An. gambiae complex specimens. These included specimens from the laboratory colonies and field samples from the Democratic Republic of Congo. Amplified DNA from these specimens, using the universal (UV) and An. leesoni species-specific primers (LEES), were sequence analysed. Additionally, An. leesoni DNA was processed through the diagnostic An. gambiae multiplex PCR to determine if this species can be misidentified as a member of the An. gambiae complex.

Results
Laboratory-colonized as well as field-collected samples of An. arabiensis, An. gambiae, Anopheles merus, Anopheles quadriannulatus, Anopheles coluzzii as well as Anopheles moucheti produced an amplicon of similar size to that of An. leesoni when using an An. funestus multiplex PCR. Sequence analysis confirmed that the UV and LEES primers amplify a segment of the ITS2 region of members of the An. gambiae complex and An. moucheti. The reverse was not true, i.e. the An. gambiae multiplex PCR does not amplify DNA from An. leesoni.

Conclusion
This investigation shows that An. arabiensis, An. gambiae, An. merus, An. quadriannulatus, An. coluzzii and An. moucheti can be misidentified as An. leesoni when using An. funestus multiplex PCR. This shows the importance of identifying specimens using standard morphological dichotomous keys as far as possible prior to the use of appropriate PCR-based identification methods. Should there be doubt concerning field-collected specimens molecularly identified as An. leesoni, the An. gambiae multiplex PCR and sequencing of the internal transcribed spacer 2 (ITS2) can be used to eliminate false identifications.
Assessment of developmental neurotoxicity induced by chemical mixtures using an adverse outcome pathway concept
Authors: Pistollato Francesca , de Gyves Emilio Mendoza , Carpi Donatella , Bopp Stephanie K. , Nunes Carolina , Worth Andrew , Bal-Price Anna 
Published: February 2020

Abstract
Background
In light of the vulnerability of the developing brain, mixture risk assessment (MRA) for the evaluation of developmental neurotoxicity (DNT) should be implemented, since infants and children are co-exposed to more than one chemical at a time. One possible approach to tackle MRA could be to cluster DNT chemicals in a mixture on the basis of their mode of action (MoA) into ‘similar’ and ‘dissimilar’, but still contributing to the same adverse outcome, and anchor DNT assays to common key events (CKEs) identified in DNT-specific adverse outcome pathways (AOPs). Moreover, the use of human in vitro models, such as induced pluripotent stem cell (hiPSC)-derived neuronal and glial cultures would enable mechanistic understanding of chemically-induced adverse effects, avoiding species extrapolation.

Methods
HiPSC-derived neural progenitors differentiated into mixed cultures of neurons and astrocytes were used to assess the effects of acute (3 days) and repeated dose (14 days) treatments with single chemicals and in mixtures belonging to different classes (i.e., lead(II) chloride and methylmercury chloride (heavy metals), chlorpyrifos (pesticide), bisphenol A (organic compound and endocrine disrupter), valproic acid (drug), and PCB138 (persistent organic pollutant and endocrine disrupter), which are associated with cognitive deficits, including learning and memory impairment in children. Selected chemicals were grouped based on their mode of action (MoA) into ‘similar’ and ‘dissimilar’ MoA compounds and their effects on synaptogenesis, neurite outgrowth, and brain derived neurotrophic factor (BDNF) protein levels, identified as CKEs in currently available AOPs relevant to DNT, were evaluated by immunocytochemistry and high content imaging analysis.

Results
Chemicals working through similar MoA (i.e., alterations of BDNF levels), at non-cytotoxic (IC20/100), very low toxic (IC5), or moderately toxic (IC20) concentrations, induce DNT effects in mixtures, as shown by increased number of neurons, impairment of neurite outgrowth and synaptogenesis (the most sensitive endpoint as confirmed by mathematical modelling) and increase of BDNF levels, to a certain extent reproducing autism-like cellular changes observed in the brain of autistic children.

Conclusions
Our findings suggest that the use of human iPSC-derived mixed neuronal/glial cultures applied to a battery of assays anchored to key events of an AOP network represents a valuable approach to identify mixtures of chemicals with potential to cause learning and memory impairment in children.