bluuebunny/crossref_metadata_2025_split huggingface dataset:
EFNA3 as a predictor of clinical prognosis and immune checkpoint therapy efficacy in patients with lung adenocarcinoma
Authors: Deng Mingming , Tong Run , Zhang Zhe , Wang Tao , Liang Chaonan , Zhou Xiaoming , Hou Gang 
Published: October 2021

Abstract
Background
Ephrin receptors (Eph) and their ligands, called ephrins, function in various disease processes. However, the expression level and prognostic value of Eph/ephrins in lung adenocarcinoma (LUAD) are still unclear.

Methods
The Oncomine and GEPIA databases were used to explore the differential expression of Eph/ephrins in LUAD. Kaplan–Meier plotter was selected to explore the prognostic value of Eph/ephrins. The cBioPortal database was used to analyze the genetic variation of the EFNA3 gene. Immunohistochemistry was used to analyze the expression level and clinical value of ephrin-A3 protein in clinical LUAD tissue. Weighted coexpression network analysis (WGCNA) and gene set enrichment analysis (GSEA) identified the potential regulatory mechanism of EFNA3. CCK-8 assays and colony-forming experiments were used to investigate whether EFNA3 can regulate cell proliferation ability in LUAD. Analysis of lactate, ATP, and glucose uptake levels was used to explore the effect of EFNA3 on glycolysis ability. In addition, we investigated the relationship between EFNA3 and tumor infiltrating immune cells (TIICs). Finally, the potential immunotherapy response prediction value of EFNA3 was also explored.

Results
In this study, we found that EFNA3 expression was significantly correlated with both overall survival (OS) and progression-free survival (PFS) in LUAD patients based on a comprehensive analysis of the Eph/Ephrin family. Next, the expression of the EFNA3 protein was increased in LUAD tissues and was designated an independent prognostic risk factor. Mechanistically, EFNA3 may be involved in nuclear division, synaptic function, and ion channel activity-related pathways. In vitro experiments confirmed the role of EFNA3 in promoting LUAD cells and showed that it could regulate glycolytic capacity. Moreover, EFNA3 was negatively associated with immunity, stromal infiltration, and several TIICs. Finally, EFNA3 was found to be positively related to multiple immunotherapy biomarkers.

Conclusions
In conclusion, increased EFNA3 in LUAD patients predicted worse clinical prognosis, promoted LUAD cell proliferation and glycolysis ability, and was related to immunotherapy response.
Antibiotic heteroresistance in Mycobacterium tuberculosis isolates: a systematic review and meta-analysis
Authors: Ye Mao , Yuan Wen , Molaeipour Leila , Azizian Khalil , Ahmadi Alireza , Kouhsari Ebrahim 
Published: October 2021

Abstract
Background
Mycobacterium tuberculosis (MTB) is responsible for tuberculosis; that continues to be a public health threat across the globe. Furthermore, increasing heteroresistance (HR)-the presence of resistant and susceptible isolates among MTB strains- has been reported from around the world. This phenomenon can lead to full resistance development and treatment failure.

Methods
We systematically searched the relevant studies in PubMed, Scopus, and Embase (Until October 21, 2020). The study outcomes revealed the weighted pooled prevalence of antibiotic HR in MTB isolates with subgroup analysis by year, quality of study, and heteroresistance detection method.

Results
A total of 38 studies which had investigated MTB isolates were included in the meta-analysis. Geographically, the highest number of studies were reported from Asia (n  =  24), followed by Africa (n  =  5). Nineteen studies reported HR to isoniazid, with a weighted pooled prevalence of 5% (95% CI 0–12) among 11,761 MTB isolates. Also, there is no important trend for the subgroup analysis by the study period (2001–2014 vs 2015–2017 vs 2018–2020). HR to rifampin was reported in 17 studies, with a weighted pooled prevalence of 7% (95% CI 2–14) among 3782 MTB isolates. HR to fluoroquinolone and ethambutol were reported in 12 and 4 studies, respectively, with weighted pooled prevalence of 10% and 1% among 2153 and 1509 MTB isolates, correspondingly.

Conclusion
Based on our analysis, HR in MTB isolates with different frequency rate is present worldwide. Thus, the selection of appropriate and reliable methods for HR detection is crucial for TB eradication.
The theoretical model of spatial production for innovation
Authors: Olah Daniel , Alpek B. Levente 
Published: October 2021

AbstractThe overall aim of the study is to create the theoretical model of spatial production for innovation, which provides a measurement basis for later research as well as providing a measurement framework for the territorial indexation of innovation. In addition, it raises the question of what factors can hinder and which can help the formation and development of the spatial production of innovation. In the context of the above, based on a chronological, multidimensional review and analysis of literature research, it summarizes and presents the possibilities of interpreting the concept of innovation, paying attention to its territorial aspects. The model presented in our study builds on the literature on the external–internal divisions of innovation barriers, but also differs in that the model simultaneously displays the socio-economic space (innovation ecosystem), the regional scales as well as time. Presenting the typological barriers to innovation and summarizing the related factors, as well as developing a model to measure the issue, can help by specifically promoting the development of regions with less innovation capacity and potential in this field, at the same time providing a basis for assessing the territorial aspects of the phenomenon, which may also support the creation of development programmes to support the resolution of territorial disparities.
Diagnostic accuracy of B-mode ultrasound, ultrasound elastography and diffusion weighted MRI in differentiation of thyroid nodules (prospective study)
Authors: Latif Mahmoud Abdel , El Rakhawy Magdy Mohamed , Saleh Mohamed Fathy 
Published: October 2021

Abstract
Background
The incidence of the thyroid nodules and its detection is increasing rapidly. The most precise method for diagnosis of the nodules of the thyroid is FNAC. But, about 10–20% of specimens of FNAC are indeterminate and non-diagnostic. Therefore, there is a demand for another diagnostic method for evaluating thyroid nodules. Thyroid ultrasound elastography may improve the ability to differentiate malignant from benign thyroid nodules. Few articles were published about the results of DW MRI in thyroid nodules, with its results confirmed that malignant nodules have lower mean ADC values than benign nodules. This study aims to investigate and compare the accuracy of B-mode ultrasound, ultrasound elastography and diffusion-weighted MRI in characterization of the nodules of the thyroid.

Results
The study included 56 patients with thyroid nodules (36 benign and 20 malignant). Thyroid ultrasound, ultrasound elastography and DWI were done for all patients. Ultrasound-guided FNA Cytological examination (as the gold standard) was done for 48 patients and surgical histopathology was done to 8 patients with non-diagnostic FNAC. The results showed: TIRADS score had sensitivity 90%, specificity 77.8% and accuracy of 82.14%. The elastography score had sensitivity 80%, specificity 88.9% and accuracy 85.7%. The use of the strain ratio had 80% sensitivity, 94.4% specificity and 89.3% accuracy. DWI and ADC value had 100% sensitivity and 94.4% specificity and the accuracy was 96.4% for differentiating malignant from benign thyroid nodules. Multi-parametric analysis by TIRADS and ADC had 100% accuracy.

Conclusion
Ultrasound elastography add valuable data over ultrasound TIRADS. But, diffusion weighted MRI and ADC value has more accuracy in differentiating malignant from benign thyroid nodules. The best performance was achieved by the combination of ACR-TIRADS and ADC value.
Development of a theory-based video-game intervention to increase advance care planning conversations by healthcare providers
Authors: Mohan Deepika , MacMartin Meredith A. , Chelen Julia S. C. , Maezes Carolyn B. , Barnato Amber E. 
Published: October 2021

Abstract
Background
Hospitalization offers an opportunity for healthcare providers to initiate advance care planning (ACP) conversations, yet such conversations occur infrequently. Barriers to these conversations include attitudes, skill, and time. Our objective was to develop a theory-based, provider-level intervention to increase the frequency of ACP conversations in hospitals.

Methods
We followed a systematic process to develop a theory-based, provider-level intervention to increase ACP conversations between providers and their hospitalized patients. Using principles established in Intervention Mapping and the Behavior Change Wheel, we identified a behavioral target, a theory of behavior change, behavior change techniques, and a mode of delivery. We addressed a limitation of these two processes of intervention development by also establishing a framework of design principles to structure the selection of intervention components. We partnered with a game development company to translate the output into a video game.

Results
We identified willingness to engage in ACP conversations as the primary contributor to ACP behavior, and attitudes as a modifiable source of this willingness. We selected self-determination theory, and its emphasis on increasing autonomous motivation, as a relevant theory of behavior change and means of changing attitudes. Second, we mapped the components of autonomous motivation (i.e., autonomy, competence, and relatedness) to relevant behavior change techniques (e.g., identity). Third, we decided to deliver the intervention using a video game and to use the narrative engagement framework, which describes the use of stories to educate, model behavior, and immerse the user, to structure our selection of intervention components. Finally, in collaboration with a game development company, we used this framework to develop an adventure video game (Hopewell Hospitalist).

Conclusions
The systematic development of a theory-based intervention facilitates the mechanistic testing of the efficacy of the intervention, including the specification of hypotheses regarding mediators and moderators of outcomes. The intervention will be tested in a randomized clinical trial.
Measuring neuropsychiatric symptoms in patients with early cognitive decline using speech analysis
Authors: König Alexandra , Mallick Elisa , Tröger Johannes , Linz Nicklas , Zeghari Radia , Manera Valeria , Robert Philippe 
Published: October 2021

Abstract

Background
Certain neuropsychiatric symptoms (NPS), namely apathy, depression, and anxiety demonstrated great value in predicting dementia progression, representing eventually an opportunity window for timely diagnosis and treatment. However, sensitive and objective markers of these symptoms are still missing. Therefore, the present study aims to investigate the association between automatically extracted speech features and NPS in patients with mild neurocognitive disorders.

Methods
Speech of 141 patients aged 65 or older with neurocognitive disorder was recorded while performing two short narrative speech tasks. NPS were assessed by the neuropsychiatric inventory. Paralinguistic markers relating to prosodic, formant, source, and temporal qualities of speech were automatically extracted, correlated with NPS. Machine learning experiments were carried out to validate the diagnostic power of extracted markers.

Results
Different speech variables are associated with specific NPS; apathy correlates with temporal aspects, and anxiety with voice quality—and this was mostly consistent between male and female after correction for cognitive impairment. Machine learning regressors are able to extract information from speech features and perform above baseline in predicting anxiety, apathy, and depression scores.

Conclusions
Different NPS seem to be characterized by distinct speech features, which are easily extractable automatically from short vocal tasks. These findings support the use of speech analysis for detecting subtypes of NPS in patients with cognitive impairment. This could have great implications for the design of future clinical trials as this cost-effective method could allow more continuous and even remote monitoring of symptoms.
Approach to the Patient: Safety of Growth Hormone Replacement in Children and Adolescents
Authors: Bamba Vaneeta , Kanakatti Shankar Roopa 
Published: October 2021

Abstract
The use of recombinant human growth hormone (rhGH) in children and adolescents has expanded since its initial approval to treat patients with severe GH deficiency (GHD) in 1985. rhGH is now approved to treat several conditions associated with poor growth and short stature. Recent studies have raised concerns that treatment during childhood may affect morbidity and mortality in adulthood, with specific controversies over cancer risk and cerebrovascular events. We will review 3 common referrals to a pediatric endocrinology clinic, followed by a summary of short- and long-term effects of rhGH beyond height outcomes. Methods to mitigate risk will be reviewed. Finally, this information will be applied to each clinical case, highlighting differences in counseling and clinical outcomes. rhGH therapy has been used for more than 3 decades. Data are largely reassuring, yet we still have much to learn about pharmaceutical approaches to growth in children and the lifelong effect of treatment.
The Ends of Media Studies
Authors: Starosielski Nicole 
Published: October 2021

AbstractThis article poses the question: what are the ends of media studies? It discusses a turn to “nature” and the elements that has pushed media studies beyond its traditional objects and subjects. While the conceptualization of environments and bodies as communicative substrates offers new avenues for media research, mediation has also been taken up in a wide range of disciplinary and intellectual contexts. Rather than establishing limits or an essential core of media studies, the article suggests that media scholars take an etic orientation and attend to the questions whose invisibility is constitutive of the field. Using the example of undersea cable systems, the article describes some of the many conceptual, institutional, and pedagogical ends of media analysis.
Sense Experiences
Authors: Gill Denise 
Published: October 2021

AbstractThis article provides an account of how sense experiences are drawn into processes of contest over the boundaries of citizenship and belonging. Based on ethnographic research in Istanbul and Ankara, it examines the ruptures of the 2016 failed coup attempt in Turkey. Particular forms of listening emerged in Western urban centers, newly attuned to sounds of warfare commingled with Islamic melodic devotionals ordered by state officials. Unique and pronounced engagements with bodily liquids accompanied the handling and placement of the dead. The multi-sensory experiences of Muslim women municipal employees who wash and shroud the deceased elucidated the foundational roles of scent and body weight in constituting martyrdom. This article demonstrates how the body politic operates—with various forms of acquiescence and repudiation—through sound, smell, and touch.
Integrated In Silico Studies on the Role of Nicotinamide Adenine Dinucleotide (NADH) Binding in Activating C-Terminal Binding Protein 2 (CtBP2)
Authors: Aoyagi Tsukasa , Yoshino Ryunosuke , Mitsuta Yuki , Morita Rikuri , Harada Ryuhei , Shigeta Yasuteru 
Published: October 2021

Abstract
The C-terminal binding protein 2 (CtBP2) plays a role in apoptosis and embryogenesis. Genetic knockout studies have been demonstrated to cause severe developmental defects and embryonic lethality. CtBP2 has three key domains and dimerizes for a significant role by binding with nicotinamide adenine dinucleotide (NADH). However, the molecular mechanism of CtBP2 dimerization and the effect of NADH binding are unknown. In this study, we performed molecular dynamics (MD) and docking simulation to reveal the mechanism of C-terminal binding protein 2 (CtBP2) dimerization and the effect of NADH binding on the dimer formation. Our MD simulation results detected seven salt bridges that are important for CtBP2 dimerization. And docking simulation demonstrated that the holo-monomer gave a higher probability of correct docking pose than the apo-monomer. Moreover, in docking simulation using a PXDLS model peptide, that holo form gave more docking poses than that apo form. These results suggested that the holo form has a structure that facilitates the formation of dimers and the binding of PXDLS peptides.
One-step Preparation of N-Unprotected Aziridines from 2H-Azirines by Addition of Ketene Silyl Acetals Catalyzed by Lewis Acids
Authors: Suzuki Itaru , Takenaka Yuya , Morishita Yoshitaka , Shibata Ikuya 
Published: October 2021

Abstract
The nucleophilic addition of ketene silyl acetals 2 into 2H-azirines 1 proceeded in the presence of Lewis acids such as InX3 or Sc(OTf)3 to give N-unprotected aziridines 3. The mild Lewis acidity of the catalyst is important for the achievement of this coupling. The generated aziridine 3 could then be transformed into either oxazolines or γ–amino carbonyls.
Synthesis of Carbazole-containing 1,2-Azaborine Derivatives Using Bora-Friedel–Crafts Reaction and Their Photophysical Properties
Authors: Yamamoto Koji , Yamada Itsuki , Kameyama Masaru , Yamamoto Koji , Nakamura Yosuke 
Published: October 2021

Abstract
Carbazole-containing 1,2-azaborine derivatives bearing various substituents were synthesized using bora-Friedel–Crafts reactions of 1,8-diphenylcarbazole derivatives, and the substituent effects on their photophysical properties were investigated. Furthermore, three carbazole-containing azaborine dimers with different annulation manners between the azaborine and benzene moieties were also successfully synthesized, and the effects of dimerization and differences in the annulation manners on their photophysical properties were disclosed.
Stratos N. Dordanas and Nikos Papanastasiou, eds., Ο «μακρύς» ελληνογερμανικός εικοστός αιώνας: Οι μαύρες σκιές στην ιστορία των διμερών σχέσεων [The “long” Greek-German twentieth century: The dark shadows in the history of the bilateral relationships]
Authors: Vachtsevanou Chrysa 
Published: October 2021

Review of Stratos N. Dordanas and Nikos Papanastasiou, eds. Ο «μακρύς» ελληνογερμανικός εικοστός αιώνας: Οι μαύρες σκιές στην ιστορία των διμερών σχέσεων [The “long” Greek-German twentieth century: The dark shadows in the history of the bilateral relationships]. Thessaloniki: Epikentro, 2018. 488 pp.
Palliative care aspects of wound healing in complex patients: a case report
Authors: Allen Latricia L , Uphold Constance R , Koniaris-Rambaud Christine , House Kim , Gray Frances , Fitzgerald Linda , Vaughan Camille , Johnson Theodore M 
Published: October 2021

Symptom or palliative management for wound care has commonly been reported in the literature as being focused on end-of-life care with less emphasis on being an effective supportive option for any patient with a wound in whom symptom management is indicated. This case report describes a frail older patient with a hard-to-heal pressure injury and multiple comorbidities to highlight palliative symptom management as a viable option to enhance patient comfort. Wound care providers may consider a palliative approach for hard-to-heal wound management that incorporates the whole patient, family and/or caregiver when faced with management of a frail older adult with a hard-to-heal wound to enhance the relief of suffering and improve quality of life. All procedures were performed in compliance with relevant laws and institutional guidelines and the appropriate institutional committee has approved them. Declaration of interest: The authors have no conflicts of interest to declare.
Community-based prevalence of rheumatic heart disease in rural Ethiopia: Five-year follow-up
Authors: Gemechu Tadesse , Parry Eldryd H. O. , Yacoub Magdi H. , Phillips David I. W. , Kotit Susy 
Published: October 2021

Background
As little is known about the prevalence and clinical progression of subclinical (latent) rheumatic heart disease (RHD) in sub-Saharan Africa, we report the results of a 5 year follow-up of a community based, echocardiographic study of the disease, originally carried out in a rural area around Jimma, Ethiopia.

Methods
Individuals with evidence of RHD detected during the baseline study as well as controls and their family members were screened with a short questionnaire together with transthoracic echocardiography.

Results
Of 56 individuals with RHD (37 definite and 19 borderline) in the original study, 36 (26 definite and 10 borderline) were successfully located 57.3 (range 44.9–70.7) months later. At follow-up two thirds of the definite cases still had definite disease; while a third had regressed. Approximately equal numbers of the borderline cases had progressed and regressed. Features of RHD had appeared in 5 of the 60 controls. There was an increased risk of RHD in the family relatives of borderline and definite cases (3.8 and 4.0 times respectively), notably among siblings. Compliance with penicillin prophylaxis was very poor.

Conclusions
We show the persistence of echocardiographically demonstrable RHD in a rural sub-Saharan population. Both progression and regression of the disease were found; however, the majority of the individuals who had definite features of RHD had evidence of continuing RHD lesions five years later. There was an increased risk of RHD in the family relatives of borderline and definite cases, notably among siblings. The findings highlight the problems faced in addressing the problem of RHD in the rural areas of sub-Saharan Africa. They add to the evidence that community-based interventions for RHD will be required, together with appropriate ways of identifying active disease, achieving adequate penicillin prophylaxis and developing vaccines for primary prevention.