bluuebunny/crossref_metadata_2025_split huggingface dataset:
Human EVI2B acts as a Janus-faced oncogene/antioncogene by differently affecting as per cancer type neoplastic cells growth and immune infiltration
Authors: Zhang Fangyingnan , Wang Xinning , Zhang Xiaoqi , Waheed Saquib , Zhong Rong , Armato Ubaldo , Wu Jun , Chiarini Anna , Prà Ilaria Dal , Zhang Chao , Li Zhibin 
Published: June 2023

Abstract

Objectives
The EVI2B (Ecotropic Viral Integration Site 2B) gene encodes a transmembrane glycoprotein pivotal in immunocytes maturation. Recent evidence implicated EV12B’s expression with human colon cancer progression. However, EVI2B’s downstream pathways affecting tumor growth and tumor-infiltrating cells remain unclear.

Methods
We first studied the diagnostic and prognostic value of EVI2B in pan-cancers by utilizing a series of in silico tools and clinical samples. Then we identified the modulated transcriptional expression and DNA methylation in high EVI2B’s expression groups of the same three cancers. We verified via RT-PCR the effect of stable EVI2B knock-down on the expression of JAK/STAT-related genes in two immune cell lines and the acceleration of proliferation in four cancer cell lines. Finally, the regulation of leukocyte infiltration was studied using TIMER.

Results
In SKCM and LUAD a heightened EVI2B’s expression promoted a better prognosis. Conversely, in LGG EVI2B’s upregulation concurred with a worse prognosis. EVI2B silencing enhanced the proliferation of the tumor cell lines. The hypermethylated genome strengthened EVI2B’s Janus-like effect in high EVI2B expressing SKCM and LUAD tumors. While the total DNA methylation was lower in high EVI2B expressing LGG. Further analysis revealed that multiple EVI2B-involved down-stream JAK-STAT genes also exhibited the Janus-like feature in SKCM, LUAD and LGG progression. Correspondingly, anti-tumor leukocytes infiltrated EVI2B high expressing SKCM and LUAD while more pro-tumor ones penetrated into EVI2B heightened LGG.

Conclusions

EVI2B acts as a Janus-faced oncogene/antioncogene by differently affecting neoplastic cell proliferation rates and tumor-promoting or tumor-hindering immunocytes’ infiltration.
Epstein–Barr virus positive gastric adenocarcinoma with systemic EBV reactivation in a patient with persistently active systemic lupus erythematosus
Authors: Miskovic Rada , Miljanovic Danijela , Dimic Cumic Maja , Lazarevic Ivana , Banko Ana 
Published: June 2023

Abstract

Objectives
Epstein–Barr virus (EBV) has been associated with several types of cancers, most often with nasopharyngeal carcinomas and hematological malignancies. It is also suggested that EBV has significant role in the pathogenesis of different types of autoimmune diseases including systemic lupus erythematosus (SEL). The exact mechanisms behind these processes are not elucidated.

Case presentation
We present a case of a 52-years old female patients with moderately active SLE presenting with severe fatigue, purpuric lesions, alopecia, polyarthritis, mucosal ulcerations, and progressive thrombocytopenia over a period of 10 months. During the work-up, the patient was evaluated for several viral infections. Serology testing showed elevation of anti-EBV, anti-CMV and anti-HSV1/2 IgM antibodies with the presence of IgG antibodies against all mentioned viruses except HSV2. Corticosteroid therapy was escalated, and azathioprine was introduced. Due to the persistence of significant thrombocytopenia and monoclonal IgG sternal puncture was performed. Morphological and immunohistochemical analysis of bone marrow specimen presented infiltration with metastatic deposits of adenocarcinoma and monoclonal plasmacytosis. Esophagogastroduodenoscopy showed multiple prepyloric erosions of gastric mucosa, which were biopsied. Pathohistological analysis demonstrated infiltration of gastric mucosa with diffuse type adenocarcinoma. Further PCR testing of biopsied gastric adenocarcinoma revealed the presence of EBV DNA in carcinoma tissue. The patient was sent to the oncologist for further evaluation.

Conclusions
Assessment of SLE patients with persistently active disease should include the analysis of the herpesvirus infection status. Reactivations of EBV may be considered as possible trigger for lupus flares and the factor for increased risk of developing malignancies.
Wnt/β-catenin signaling activation by TIMP1 confers cisplatin-resistant gastric cancer cells to malignant behaviors and epithelial–mesenchymal transition
Authors: Zhu Feng , He Xiaogu , Shuang Fen , Fang Xiangming , Jiang Jinxia 
Published: June 2023

Abstract

Objectives
Cisplatin (DDP) remains to be commonly employed in treating gastric cancer (GC) patients, particularly advanced-stage ones. However, acquired resistance to DDP often occurs, which causes a poor prognosis. This study aimed to understand the potential contribution of tissue inhibitor of metalloproteinase 1 (TIMP1) in acquired resistance to DDP in GC.

Methods
Bioinformatics analysis was performed to explore the relation of TIMP1 expression with stages and survival rate in GC. The TIMP1 expression between the parental and DDP-resistant GC cell lines were detected by quantitative reverse-transcription polymerase chain reaction (qRT-PCR). The effect of TIMP1 on the ability of cells against DDP was elevated by CCK-8, wounding healing, and transwell assays after exposing DDP. The role of TIMP1 in stemness and EMT process was explored through spheres formation assay and detecting stem cell- and EMT-related markers. Finally, the regulation of TIMP1 in Wnt/β-catenin signaling in DDP-resistant GC cells was also analyzed by western blot.

Results
Bioinformatics analysis revealed that TIMP1 is highly expressed and closely related to tumor stage and poor survival in GC. The TIMP1 expression of DDP-resistant GC cell lines was significantly higher than that of the parental one. CCK-8, wounding healing, and transwell assays showed that the tolerance to DDP of DDP-resistant AGS (AGS/DDP) cells was significantly augmented compared with that of parental AGS cells, revealed by increased IC50 and enhanced migration and invasion when exposed to DDP. Stronger stemness and epithelial–mesenchymal transition could be also observed in AGS/DDP cells. These malignant phenotypes were eliminated by silencing TIMP1 but aggravated by overexpressing TIMP1 in AGS/DDP cells. The use of the Wnt/β-catenin inhibitor could effectively reverse the function of TMIP1 overexpression in AGS/DDP cells, which suggested that the role of TIMP1 in DDP resistance relied on the Wnt/β-catenin signaling.

Conclusions
TIMP1 is an essential regulator of DDP resistance in GC, which may be a potential therapeutic target for cases that are refractory to DDP.
Knockdown of pyruvate kinase M2 suppresses bladder cancer progression
Authors: Luo Guang-Cheng , Xu Ran , Zhang Xi , Xu Lin , Zhao Xiao-Kun , Wang Xin-Jun 
Published: June 2023

Abstract

Objectives
Bladder cancer (BCa) is one of the most frequently diagnosed cancers of the urinary tract and has a high mortality. The M2 splice isoform of pyruvate kinase (PKM2) is a key regulator of the Warburg effect in cancer cells. This study aimed to evaluate metabolic alterations and biological behaviours after knocking down PKM2.

Methods
In this study, 36 pairs of BCa tissues and adjacent normal tissues were collected to analyse the expression level of PKM2 and to explore the relationship between PKM2 level and tumour and patient status. After PKM2 knockdown in T24 cells, cell survival, migration, invasion, glucose uptake, lactate production, and apoptosis were detected. The tumour-forming ability of PKM2-reducing T24 cells was examined in vivo.

Results
The results showed that PKM2 expression correlates with BCa stage and grade. PKM2 knockdown decreases glucose consumption and lactate production and suppresses cell proliferation, migration, and invasion while increasing reactive oxygen species levels and apoptosis in T24 BCa cells in vitro. In nude mouse models, PKM2 knockdown reduced xenograft and orthotopic tumour size. Moreover, PKM2 knockdown decreased vimentin and fibronectin expression and increased E-cadherin expression. Analysis of high-throughput sequencing data revealed that PKM2 may also be associated with biological processes and diseases.

Conclusions
Overall, these results indicate that PKM2 may be a therapeutic target for BCa patients.
Hsa_circ_0079598 acts as a potential diagnostic and prognostic biomarker for gastric cancer
Authors: Xu Huiting , Cao Xiaoli , Zhang Xiaoxia , Xue Yajing , Chen Bingyan , Wang Feng , Sun Yajun 
Published: June 2023

Abstract

Objectives
The work discussed the expression level circular RNA (circRNA) hsa_circ_0079598 for gastric cancer (GC) patients as well as clinicopathological significance.

Methods
qRT-PCR was utilized for determining the expression level of hsa_circ_0079598 in GC cell lines, 40 GC tissue pairs and their paracancerous tissue specimens, 60 pairs of preoperative and postoperative plasma specimens of GC patients, 20 plasma specimens of patients with gastric polyps, and 60 plasma specimens of the healthy control group. Besides, the correlation with clinicopathological parameters was analyzed. Tumor indices glycan antigen 199 (CA199), glycan antigen 724 (CA724), and pepsinogen I (PGI) were combined to evaluate their auxiliary diagnostic value. The values of hsa_circ_0079598 in the prognosis of GC patients were analyzed using survival curves.

Results
The relative expression of hsa_circ_0079598 in the cancerous tissues of GC patients was lower than that of their paracancerous tissues (p=0.004). The relative expression of plasma hsa_circ_0079598 in GC patients was lower than that of the healthy control group (p<0.001) and patients with gastric polyps. Moreover, the relative expression of human gastric epithelial cell lines (GES-1) (p<0.05) was higher than that of hsa_circ_0079598 of HGC-27, AGS, and MGC-803 cancer cell lines in GC cell lines. The total survival time of the high-expression patient group (p=0.040) was higher than that of hsa_circ_0079598 in the low-expression patient group. The expression of hsa_circ_0079598 in patients with the tissues and plasma of GC was related to the differentiated degree of tumors and TNM staging (p<0.05). The auxiliary diagnostic value of hsa_circ_0079598 for GC was analyzed using ROC curves. When GC was distinguished from gastric polyps and the healthy control group, the areas under the ROC curve (AUCs) were 0.856 and 0.930, respectively. Hsa_circ_0079598 combined with tumor indices CA199, CA724, and PGI detection had higher specificity and accuracy than those of a single index.

Conclusions
Hsa_circ_0079598 was low-expression in cell lines, plasma, and GC tissues, which was related to the progress and prognosis of GC. Hsa_circ_0079598 combined with CA199, CA724, and PGI detection can improve the diagnosis of GC.
Individual differences in attention control and the processing of phonological contrasts in a second language
Authors: Mora Joan C. , Darcy Isabelle 
Published: June 2023

Abstract
This study investigated attention control in L2 phonological processing from a cognitive individual differences perspective, to determine its role in predicting phonological acquisition in adult L2 learning. Participants were 21 L1-Spanish learners of English, and 19 L1-English learners of Spanish. Attention control was measured through a novel speech-based attention-switching task. Phonological processing was assessed through a speeded ABX categorization task (perception) and a delayed sentence repetition task (production). Correlational analyses indicated that learners with more efficient attention switching skill and faster speed in correctly identifying the target phonetic features in the speech dimension under focus could perceptually discriminate L2 vowels at higher processing speed, but not at higher accuracy rates. Thus, attentional flexibility provided a processing advantage for difficult L2 contrasts but did not predict the extent to which precise representations for the target L2 vowels had been established. However, attention control was related to L2 learners’ ability to distinguish the contrasting L2 vowels in production. In addition, L2 learners’ accuracy in perceptually distinguishing between two contrasting vowels was significantly related to how much of a quality distinction between them they could make in production.
Was Schweizer Hausärztinnen und Hausärzte glauben und welchen Einfluss des Glaubens sie bei ihren Patientinnen und Patienten beobachten
Authors: Hefti Rene , Eglin Micha , Leiggener Christoph 
Published: June 2023

Zusammenfassung

Hintergrund: Über die Religiosität von Ärztinnen und Ärzten gibt es kaum empirische Daten. Die vorliegende Studie untersucht die religiösen Haltungen und Überzeugungen von Schweizer Hausärztinnen und Hausärzten (HÄÄ) und ihre Wahrnehmungen hinsichtlich der Bedeutung des Glaubens bei ihren Patientinnen und Patienten (PAA).

Methodik: Eine repräsentative Stichprobe von 105 HÄÄ in der Nordwestschweiz wurde mit einem validierten, webbasierten Fragebogen untersucht.

Ergebnisse: 76.2 % der HÄÄ ordneten sich dem Christentum zu und 18.1 % fühlten keiner Religionsgemeinschaft zugehörig. 20.0 % stuften sich als ziemlich bis sehr religiös ein. 41.9 % gaben an, oft bis sehr oft über religiöse Themen nachdenken und 58.1 % glauben an Gott, eine Gottheit oder etwas Göttliches.
48.6 % der HÄÄ waren der Meinung, dass Religiosität den PAA hilft, Krankheit und Leiden zu bewältigen. 41.9 % sahen aber auch, dass der Glaube Angst- und Schuldgefühle fördern und damit Leiden verstärken kann. Die Wahrnehmung der günstigen Wirkungen korrelierte signifikant mit der religiösen Haltung der HÄÄ.

Schlussfolgerung: Die vorliegende Studie erfasste erstmals empirische Daten zum „religiösen Profil“ von Schweizer Hausärztinnen und Hausärzten. Die HÄÄ zeigen eine Offenheit für die Religiosität ihrer PAA, insbesondere da, wo sich diese für die Krankheitsbewältigung als hilfreich erweist. Dies wäre ein möglicher Ausgangspunkt für die Implementierung von Spiritual Care in die Hausarztmedizin.
Die spirituelle Anamnese aus ärztlicher und patientenseitiger Sicht – eine Gegenüberstellung im Rahmen des Projekts HoPES3
Authors: Straßner Cornelia , Mächler Ruth , Sturm Noemi , Valentini Jan , Stolz Regina , Joos Stefanie , Frick Eckhard 
Published: June 2023

Zusammenfassung

Hintergrund: Im Rahmen der HoPES3-Studie wurde die Implementierung einer spirituellen Anamnese (SA) in hausärztlichen Praxen mittels einer cluster-randomisierten Studie untersucht. Es blieb bisher offen, wie stark die Diskrepanzen zwischen ärztlicher und patientenseitiger Sicht bei der Bewertung der SA im Einzelfall waren.

Forschungsfragen: Wie unterscheiden sich die Einschätzungen von Ärzt/innen und Patient/innen bezüglich der Fragen, ob die SA stattfand, wie lange sie dauerte und inwieweit sie nützlich bzw. belastend für die Patient/innen war? Welche Erklärungsgründe lassen sich für abweichende Einschätzungen identifizieren?

Methode: Die Hausärzt/innen der Interventionsgruppe boten den Studienteilnehmenden eine SA an. Beide wurden gebeten, jede spirituelle Anamnese mittels eines kurzen Fragebogens unabhängig voneinander zu bewerten. Für die Auswertung wurden die Antworten in jedem Einzelfall gegenübergestellt.

Ergebnisse: Ausgewertet wurden 133 Bewertungsbögen von 14 Hausärzten/Hausärztinnen sowie von 133 zugehörige Patienten/Patientinnen. Es bestand in mehreren Fällen Uneinigkeit darüber, ob eine SA stattgefunden hatte, wie lange sie gedauert hatte und wie belastend/hilfreich sie gewesen war. Meist waren die Einschätzungen der Patient/innen positiver als die der Ärzte/Ärtinnen. Die Freitextnennungen zeigen, dass nonverbale Kommunikation und ungeprüfte Annahmen hierbei eine Rolle spielten.

Diskussion und Schlussfolgerung: Die SA kann aus ärztlicher und patientenseitiger Sicht sehr unterschiedlich wahrgenommen werden. Häufige Gründe, die zu solchen Divergenzen und möglicherweise Missverständnissen führen, sollten in Schulungen thematisiert werden.
Properties and special phenomena of strain sensors made of carbon particle-filled elastomers
Authors: Mersch Johannes , Gerlach Gerald 
Published: June 2023

Abstract
Elastomers with a percolative network of carbon particles are a frequently studied class of materials for applications requiring high elongation and compliant sensors. For novel applications such as soft robots or smart textiles, these have some advantages over traditional strain gauges. However, their functionality is not fully understood. In this work, such materials are investigated as strain sensors in terms of their dynamic behavior, and their current limitations are demonstrated. It becomes clear that such sensors exhibit a non-monotonic behavior under dynamic loads that differs significantly from that observed in quasi-static tests. Two strategies for improving sensor characteristics are derived, modeled, and experimentally tested using the results and an electro-mechanical network model. First, a melt-spinning process that orients the carbon nanotube particles in the process direction creates different degrees of anisotropy. Second, to generate a local negative transverse contraction, an additional auxetic support structure is used. While the resulting anisotropy is insufficient to improve sensor properties, the auxetic structure can significantly improve strain sensitivity.
„Das Ethische ist kein Sachverhalt“
Authors: Vossenkuhl Wilhelm 
Published: June 2023

Abstract

“The ethical is no fact of the matter.” On Wittgenstein’s ethical paradox discusses Wittgenstein’s “Lecture on Ethics” of 1929. In this lecture to the Heretics Society at Cambridge he proposes an ethical paradox based on two incompatible types of facts, the natural facts offered by science and the supernatural facts, which he claims to be the core of ethics. The paradox is partly due to his Tractarian belief that ethics has no descriptive content. Yet, although it has no descriptive content the ethical is represented by a feeling which has a metaphysical and an undeniable factual character too, as Wittgenstein claims. This kind of fact is his personal, private if not solipsistic feeling. The paper tries to clarify this highly controversial type of feeling. It seems probable that the change from the Tractatus to the Philosophical Investigations resolves the ethical paradox along the new therapeutical lines of PU. It is argued that this is not the case. The content of the ethical paradox remains unchanged.
Análise dos Objetivos Educacionais de um Curso Técnico em Administração pela Taxonomia de Bloom Revisada
Authors: Marchesan Michele Roos , Kuhn Malcus Cassiano 
Published: June 2023

O artigo analisa os objetivos educacionais de um Curso Técnico em Administração, de um Instituto Federal, pela Taxonomia de Bloom Revisada. Realiza-se a análise dos objetivos das 21 disciplinas desse Curso, ministradas no segundo semestre de 2015, e dos objetivos do Curso como um todo, por meio de seu projeto pedagógico. A partir da Tabela Bidimensional da Taxonomia de Bloom Revisada, foram consideradas a dimensão do conhecimento e a dimensão do processo cognitivo. Verificou-se coerência dos objetivos na dimensão do conhecimento, com ênfase no conhecimento procedural e no conhecimento conceitual. Na dimensão do processo cognitivo, os objetivos contidos nos planos de ensino enfatizam as categorias de entender, aplicar e lembrar o conhecimento, enquanto os objetivos do projeto pedagógico concentram-se nas categorias aplicar e entender, nesta ordem.
A Novel Approach to Study Coherent γ-Band Oscillations in Hippocampal Brain Sections
Authors: Rodríguez Díaz Jean C. , Jenkins Paul M. , Pritchett Dominique L. , Jones Kevin S. 
Published: June 2023

Abstractγ-Band oscillations (GBOs) are generated by fast-spiking interneurons (FSIs) and are critical for cognitive functions. Abnormalities in GBOs are frequently observed in schizophrenia and bipolar disorder and are strongly correlated with cognitive impairment. However, the underlying mechanisms are poorly understood. Studying GBOs inex vivopreparations is challenging because of high energy demands and the need for continuous oxygen delivery to the tissue. As a result, GBOs are typically studied in brain tissue from very young animals or in experimental setups that maximize oxygen supply but compromise spatial resolution. Thus, there is a limited understanding of how GBOs interact within and between different brain structures and in brain tissue from mature animals. To address these limitations, we have developed a novel approach for studying GBOs inex vivohippocampal slices from mature animals, using 60-channel, perforated microelectrode arrays (pMEAs). pMEAs enhance oxygen delivery and increase spatial resolution in electrophysiological recordings, enabling comprehensive analyses of GBO synchronization within discrete brain structures. We found that transecting the Schaffer collaterals, a neural pathway within the hippocampus, impairs GBO coherence between CA1 and CA3 subfields. Furthermore, we validated our approach by studying GBO coherence in anAnk3mutant mouse model exhibiting inhibitory synaptic dysfunction. We discovered that GBO coherence remains intact in the CA3 subfield of these mutant mice but is impaired within and between the CA1 subfield. Overall, our approach offers significant potential to characterize GBOs inex vivobrain sections of animal models, enhancing our understanding of network dysfunction in psychiatric disorders.
Axon Fasciculation, Mediated by Transmembrane Semaphorins, Is Critical for the Establishment of Segmental Specificity of Corticospinal Circuits
Authors: Gu Zirong , Matsuura Ken , Letelier Agustin , Basista Mark , Craig Corey , Imai Fumiyasu , Yoshida Yutaka 
Published: June 2023

Axon fasciculation is thought to be a critical step in neural circuit formation and function. Recent studies have revealed various molecular mechanisms that underlie axon fasciculation; however, the impacts of axon fasciculation, and its corollary, defasciculation, on neural circuit wiring remain unclear. Corticospinal (CS) neurons in the sensorimotor cortex project axons to the spinal cord to control skilled movements. In rodents, the axons remain tightly fasciculated in the brain and traverse the dorsal funiculus of the spinal cord. Here we show that plexinA1 (PlexA1) and plexinA3 (PlexA3) receptors are expressed by CS neurons, whereas their ligands, semaphorin-5A (Sema5A) and semaphorin-5B (Sema5B) are expressed in the medulla at the decussation site of CS axons to inhibit premature defasciculation of these axons. In the absence of Sema5A/5B-PlexA1/A3 signaling, some CS axons are prematurely defasciculated in the medulla of the brainstem, and those defasciculated CS axons aberrantly transverse in the spinal gray matter instead of the spinal dorsal funiculus. In the absence of Sema5A/Sema5B-PlexA1/A3 signaling, CS axons, which would normally innervate the lumbar spinal cord, are unbundled in the spinal gray matter, and prematurely innervate the cervical gray matter with reduced innervation of the lumbar gray matter. In bothSema5A/5BandPlexA1/A3mutant mice (both sexes), stimulation of the hindlimb motor cortex aberrantly evokes robust forelimb muscle activation. Finally,Sema5A/5BandPlexA1/A3mutant mice show deficits in skilled movements. These results suggest that proper fasciculation of CS axons is required for appropriate neural circuit wiring and ultimately affect the ability to perform skilled movements.SIGNIFICANCE STATEMENTAxon fasciculation is believed to be essential for neural circuit formation and function. However, whether and how defects in axon fasciculation affect the formation and function of neural circuits remain unclear. Here we examine whether the transmembrane proteins semaphorin-5A (Sema5A) and semaphorin-5B (Sema5B), and their receptors, plexinA1 (PlexA1) and plexinA3 (PlexA3) play roles in the development of corticospinal circuits. We find that Sema5A/Sema5B and PlexA1/A3 are required for proper axon fasciculation of corticospinal neurons. Furthermore,Sema5A/5BandPlexA1/A3mutant mice show marked deficits in skilled motor behaviors. Therefore, these results strongly suggest that proper corticospinal axon fasciculation is required for the appropriate formation and functioning of corticospinal circuits in mice.