bluuebunny/crossref_metadata_2025_split huggingface dataset:
miRNome and Functional Network Analysis of PGRMC1 Regulated miRNA Target Genes Identify Pathways and Biological Functions Associated With Triple Negative Breast Cancer
Authors: Pedroza Diego A. , Ramirez Matthew , Rajamanickam Venkatesh , Subramani Ramadevi , Margolis Victoria , Gurbuz Tugba , Estrada Adriana , Lakshmanaswamy Rajkumar 
Published: July 2021

BackgroundIncreased expression of the progesterone receptor membrane component 1, a heme and progesterone binding protein, is frequently found in triple negative breast cancer tissue. The basis for the expression of PGRMC1 and its regulation on cellular signaling mechanisms remain largely unknown. Therefore, we aim to study microRNAs that target selective genes and mechanisms that are regulated by PGRMC1 in TNBCs.MethodsTo identify altered miRNAs, whole human miRNome profiling was performed following AG-205 treatment and PGRMC1 silencing. Network analysis identified miRNA target genes while KEGG, REACTOME and Gene ontology were used to explore altered signaling pathways, biological processes, and molecular functions.ResultsKEGG term pathway analysis revealed that upregulated miRNAs target specific genes that are involved in signaling pathways that play a major role in carcinogenesis. While multiple downregulated miRNAs are known oncogenes and have been previously demonstrated to be overexpressed in a variety of cancers. Overlapping miRNA target genes associated with KEGG term pathways were identified and overexpression/amplification of these genes was observed in invasive breast carcinoma tissue from TCGA. Further, the top two genes (CCND1 and YWHAZ) which are highly genetically altered are also associated with poorer overall survival.ConclusionsThus, our data demonstrates that therapeutic targeting of PGRMC1 in aggressive breast cancers leads to the activation of miRNAs that target overexpressed genes and deactivation of miRNAs that have oncogenic potential.
Extract From Tetrastigma hemsleyanum Leaf Alleviates Pseudomonas aeruginosa Lung Infection: Network Pharmacology Analysis and Experimental Evidence
Authors: Lou Tian-ling , Ji Tao , Peng Xin , Ji Wei-wei , Yuan Li-xia , Wang Juan , Li Shi-min , Zhang Shun , Shi Qiao-yun 
Published: July 2021

Tetrastigma hemsleyanum Diels &amp; Gilg (T. hemsleyanum) has attracted much attention due to its ability on pneumonia, bronchitis, and immune-related diseases, while its functional components and underlying mechanism of action on pneumonia have not been fully elucidated. Herein, we used a systematic network pharmacology approach to explore the action mechanism of T. hemsleyanum leaf in the treatment of pneumonia. In this study, the results of network pharmacology demonstrated that there were 34 active components and 80 drug–disease targets in T. hemsleyanum leaf, which were strongly in connection with signal transduction, inflammatory response, and the oxidation–reduction process. Subsequently, a mouse model of pneumonia induced by Pseudomonas aeruginosa (P. aeruginosa) was established to validate the predicted results of network pharmacology. In the animal experiments, aqueous extract of T. hemsleyanum leaf (EFT) significantly attenuated the histopathological changes of lung tissue in P. aeruginosa–induced mice and reduced the number of bacterial colonies in BALFs by 96.84% (p &lt; 0.01). Moreover, EFT treatment suppressed the increase of pro-inflammatory cytokines IL-17, IL-6, and TNF-α in lung tissues triggered by P. aeruginosa, which led to the increase of Th17 cells (p &lt; 0.05). High concentration of EFT treatment (2.0 g/kg) obviously increased the anti-inflammatory cytokine levels, accompanied by the enhancement of Treg proportion in a dose-dependent manner and a notable reversal of transcription factor RORγt expression. These findings demonstrated that network pharmacology was a useful tool for TCM research, and the anti-inflammatory effect of EFT was achieved by maintaining Th17/Treg immune homeostasis and thereby suppressing the inflammatory immune response.
Glucagon-Like Peptide-1 Analog Exendin-4 Ameliorates Cocaine-Mediated Behavior by Inhibiting Toll-Like Receptor 4 Signaling in Mice
Authors: Zhu Changliang , Tao Hong , Rong Shikuo , Xiao Lifei , Li Xinxiao , Jiang Shucai , Guo Baorui , Wang Lei , Ding Jiangwei , Gao Caibing , Chang Haigang , Sun Tao , Wang Feng 
Published: July 2021

Exendin-4 (Ex4), a long-lasting glucagon-like peptide-1 analog, was reported to exert favourable actions on inhibiting cocaine-associated rewarding and reinforcing effects of drug in animal models of addiction. However, the therapeutic potential of different dose of GLP-1 receptor agonist Ex4 in different behavioral paradigms and the underlying pharmacological mechanisms of action are incompletely understood. Herein, we firstly investigated the effects of Ex4 on cocaine-induced condition place preference (CPP) as well as extinction and reinstatement in male C57BL/6J mice. Additionally, we sought to elucidate the underlying pharmacological mechanism of these actions of Ex4. The paradigm of cocaine-induced CPP was established using 20 mg/kg cocaine or saline alternately during conditioning, while the reinstatement paradigm was modeled using 10 mg/kg cocaine on the reinstatement day. Different dose of Ex4 was administrated intraperitoneally either during conditioning or during extinction state or only on the test day. To elucidate the molecular mechanism underlying the potential effects of Ex4 on maladaptive behaviors of cocaine, the TLR4-related inflammation within the hippocampus was observed by immunofluorescence staining, and the expression levels of toll-like receptor 4 (TLR4), tumor necrosis factor (TNF)-α, and interleukin (IL)-1β were detected by Western blotting. As a consequence, systemic administration of different dose of Ex4 was sufficient to inhibit the acquisition and expression of cocaine-induced CPP, facilitate the extinction of cocaine-associated reward and attenuate reinstatement of cocaine-induced behavior. Furthermore, Ex4 treatment diminished expression levels of TLR4, TNF-α, and IL-1β, which were up-regulated by cocaine exposure. Altogether, our results indicated that Ex4 effectively ameliorated cocaine-induced behaviors likely through neurobiological mechanisms partly attributable to the inhibition of TLR4, TNF-α and IL-1β in mice. Consequently, our findings improved our understanding of the efficacy of Ex4 for the amelioration of cocaine-induced behavior and suggested that Ex4 may be applied as a drug candidate for cocaine addiction.
Pharmacotherapeutic Patterns and Patients’ Access to Pharmacotherapy for Some Rare Diseases in Bulgaria – A Pilot Comparative Study
Authors: Kamusheva Maria , Dimitrova Maria , Tachkov Konstantin , Petrova Guenka , Mitkova Zornitsa 
Published: July 2021

Provision of the latest innovative and advanced therapies for rare diseases (RDs) patients, following the international therapeutic recommendations, is crucial and necessary for both practitioners and patients. The goal is to assess the access of Bulgarian patients with the most cost-consuming RDs to medicines and to compare the pharmacotherapeutic patterns in Bulgaria and the relevant European professional associations. Pharmaco-therapeutic guidelines for treating the most cost-consuming RDs in Bulgaria were analyzed to assess their compliance with the European ones. Market entrance was evaluated through analysis of the availability of medicines in the Positive Drug List (PDL) and their date of inclusion since marketing authorization. Guidelines’ compliance index was calculated and patient access was analyzed through evaluation of the National Health Insurance Fund (NHIF) standards, which provide additional criteria for treatment initiation. The analyzed guidelines follow the adopted recommendations by the relevant European professional associations. NHIF have exclusion and inclusion criteria for initiating treatment with medicines for rare diseases and for continuation. The average time-lag between centralized procedure approval and inclusion in the Bulgarian PDL for orphan medicinal products (MPs) is 6.75 years (SD = 4.96) with the longest time observed for eptacog alfa (20 years) and the shortest for rurioctocog alfa pegol, octocog alfa and simoctocog alfa (1 year). Bulgarian patients with cystic fibrosis with pulmonary manifestation had a wait time of only 1.6 years to get access to innovative, centrally authorized medicines, whereas the period for access to acromegaly treatment was 8.2 years. The main factors influencing market entrance and patient access are the time to inclusion in the PDL and the NHIF criteria.
Exercise Intensity and Pacing Pattern During a Cross-Country Olympic Mountain Bike Race
Authors: Næss Steffan , Sollie Ove , Gløersen Øyvind Nøstdahl , Losnegard Thomas 
Published: July 2021

Objective: To examine the power profiles and pacing patterns in relation to critical power (CP) and maximal aerobic power (MAP) output during a cross-country Olympic (XCO) mountain bike race.Methods: Five male and two female national competitive XCO cyclists completed a UCI Cat. 1 XCO race. The races were 19 km and 23 km and contained five (female) and six (male) laps, respectively. Power output (PO) during the race was measured with the cyclists’ personal power meters. On two laboratory tests using their own bikes and power meters, CP and work capacity above CP (W') were calculated using three time trials of 12, 7, and 3 min, while MAP was established based on a 3-step submaximal test and the maximal oxygen uptake from the 7-min time trial.Results: Mean PO over the race duration (96 ± 7 min) corresponded to 76 ± 9% of CP and 63 ± 4% of MAP. 40 ± 8% of race time was spent with PO &gt; CP, and the mean duration and magnitude of the bouts &gt;CP was ~8 s and ~120% of CP. From the first to last lap, time &gt;CP and accumulated W' per lap decreased with 9 ± 6% and 45 ± 17%, respectively. For single &gt;CP bouts, mean magnitude and mean W' expended decreased by 25 ± 8% and 38 ± 15% from the first to the last lap, respectively. Number and duration of bouts did not change significantly between laps.Conclusion: The highly variable pacing pattern in XCO implies the need for rapid changes in metabolic power output, as a result of numerous separate short-lived &gt;CP actions which decrease in magnitude in later laps, but with little lap-to-lap variation in number and duration.
The Introduction of Medication-Free Mental Health Services in Norway: An Analysis of the Framing and Impact of Arguments From Different Standpoints
Authors: Nyttingnes Olav , Rugkåsa Jorun 
Published: July 2021

Introduction: Debates about coercive practices have challenged a traditional biomedical hegemony in mental health care. The perspectives of service user organizations have gained considerable ground, such as in the development of the Convention on the Rights of Persons with Disabilities. Such changes are often contested, and might in practice be a result of (implicit) negotiation between stakeholders with different discursive positions. To improve understanding of such processes, and how discursive positions may manifest and interact, we analyzed texts published over a 10 year period related to the introduction of medication-free inpatient services in Norway.Methods: We conducted qualitative analyses of 36 policy documents related to the introduction of medication-free services and 75 opinion pieces from a subsequent debate. We examined discursive practices in these texts as expressions of what is perceived as legitimate knowledge upon which to base mental health care from the standpoints of government, user organizations and representatives of the psychiatric profession. We paid particular attention to how standpoints were framed in different discourse surrounding mental health care, and how these interacted and changed during the study period (2008–2018).Results: The analysis shows how elements from the discourse promoted by service user organizations—most notably the legitimacy of personal experiences as a legitimate source of knowledge—entered the mainstream by being incorporated into public policy. Strong reactions to this shift, firmly based in biomedical discourse, endorsed evidence-based medicine as the authoritative source of knowledge to ensure quality care, although accepting patient involvement. Involuntary medication, and how best to help those with non-response to antipsychotic medication represented a point at which discursive positions seemed irreconcilable.Conclusion: The relative authorities of different sources of knowledge remain an area of contention, and especially in determining how best to help patients who do not benefit from antipsychotics. Future non-inferiority trials of medication-free services may go some way to break this discursive deadlock.
Cognitive Dysfunction in Insomnia Phenotypes: Further Evidence for Different Disorders
Authors: Olaithe Michelle , Ree Melissa , McArdle Nigel , Donaldson Sara , Pushpanathan Maria , Eastwood Peter R. , Bucks Romola S. 
Published: July 2021

Study Objectives: To determine cognitive profiles in individuals with short sleep duration insomnia (SSDI) and normal sleep duration insomnia (NSDI; also, paradoxical insomnia), compared to healthy sleepers.Method: Polysomnographic (PSG) and neuropsychological data were analysed from 902 community-based Raine Study participants aged 22 ± 0.6 years of whom 124 met criteria for insomnia (53 with NSDI and 71 with or SSDI) and 246 were classified as healthy with normal sleep (i.e., without insomnia or other sleep disorders). Measurements of self- report (attention and memory) and laboratory-assessed (attention, episodic memory, working memory, learning, and psychomotor function) cognition and mood, and PSG-based sleep stages (% total sleep time; %TST) were compared between these 3 groups.Results: In comparison to the healthy sleeper group, both insomnia groups had poorer self-reported attention, memory, mood, and sleep, and poorer laboratory-assessed attention (inconsistency). The NSDI group had less consistent working memory reaction time than healthy-sleepers or those with SSDI. The SSDI group had more inconsistency in executive function (shifting), and showed greater %TST in stage N1 and N3, and less REM sleep than either healthy-sleepers or those with NSDI.Conclusions: Individuals with NSDI demonstrated greater working memory inconsistency, despite no laboratory assessed sleep problems, implicating early signs of pathophysiology other than disturbed sleep. Those with SSDI demonstrated different sleep architecture, poorer attention (inconsistency), and greater executive function (inconsistency) compared to healthy-sleepers and those with NSDI, implicating sleep disturbance in the disease process of this phenotype.
Promising Anticancer Activities of Alismatis rhizome and Its Triterpenes via p38 and PI3K/Akt/mTOR Signaling Pathways
Authors: Jang Eungyeong , Lee Jang-Hoon 
Published: July 2021

The flowering plant genus Alisma, which belongs to the family Alismataceae, comprises 11 species, including Alisma orientale, Alisma canaliculatum, and Alisma plantago-aquatica. Alismatis rhizome (Ze xie in Chinese, Takusha in Japanese, and Taeksa in Korean, AR), the tubers of medicinal plants from Alisma species, have long been used to treat inflammatory diseases, hyperlipidemia, diabetes, bacterial infection, edema, oliguria, diarrhea, and dizziness. Recent evidence has demonstrated that its extract showed pharmacological activities to effectively reverse cancer-related molecular targets. In particular, triterpenes naturally isolated from AR have been found to exhibit antitumor activity. This study aimed to describe the biological activities and plausible signaling cascades of AR and its main compounds in experimental models representing cancer-related physiology and pathology. Available in vitro and in vivo studies revealed that AR extract possesses anticancer activity against various cancer cells, and the efficacy might be attributed to the cytotoxic and antimetastatic effects of its alisol compounds, such as alisol A, alisol B, and alisol B 23-acetate. Several beneficial functions of triterpenoids found in AR might be due to p38 activation and inhibition of the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR) signaling pathways. Moreover, AR and its triterpenes inhibit the proliferation of cancer cells that are resistant to chemotherapy. Thus, AR and its triterpenes may play potential roles in tumor attack, as well as a therapeutic remedy alone and in combination with other chemotherapeutic drugs.
Analisis Kualitas Aplikasi OrangeHRM Menggunakan WebQual 4.0 Dalam Mempengaruhi Kepuasan Karyawan dan Produktivitas Kerja
Authors: Wijonarko Gugus , Wirapraja Alexander 
Published: July 2021

Sumber daya manusia merupakan aspek vital dalam pengembangan bisnis perusahaan, utamanya untuk meningkatkan layanan kepada stakeholder termasuk pelanggan, maka hal yang diperlukan terlebih dahulu adalah membenahi aspek internal. Penggunaan pencatatan secara konvensional sudah dianggap tidak relevan dengan era digital saat ini. Bilamana perusahaan ingin meningkatkan daya saingnya maka diperlukan pemanfaatan teknologi dalam operasional pekerjaan yang mereka lakukan, salah satunya adalah mengembangan peran teknologi dan informasi dalam departemen manajemen sumber daya manusia dengan menerapkan aplikasi opensource berbasis web yaitu OrangeHRM. Dalam penelitian ini dilakukan dengan pendekatan terhadap pengguna aplikasi OrangeHRM dengan mengambil sampel pengguna yang bekerja pada departemen sumber daya manusia, untuk menguji hubungan antar variabel dengan menggunakan tiga variabel yaitu kualitas website (Webqual 4.0) sebagai variabel untuk mengukur persepsi kualitas dari aplikasi OrangeHRM terhadap pengguna melalui tiga indikator, yaitu kualitas informasi, interaksi layanan dan faktor penggunaan, variabel kepuasan karyawan sebagai bentuk perasaan karyawan dalam menggunakan aplikasi dan variabel produktivitas kerja yang merupakan tingkat perubahan yang dialami oleh karyawan setelah menggunakan OrangeHRM. Metode pengukuran menggunakan analisis SEM, sedangkan pengambilan sampel penelitian dilakukan dengan metode pengambilan sampel secara purposive sampling terhadap 120 responden. Hasil yang didapatkan adalah variabel Webqual 4.0 memiliki pengaruh terhadap kepuasan karyawan dan berdampak kepada meningkatnya efektivitas dan produktivitas pekerjaan yang dilakukan di departemen sumber daya manusia perusahaan setiap responden.
Dimeric aza-BODIPY and Dichloro-aza-BODIPY: A DFT Study
Authors: ÇINAR Mehmet Emin 
Published: July 2021

Density functional theory (DFT) computations were performed to unveil the electronic structures and the Kohn-Sham Molecular Orbitals (MOs) of the dimeric aza-BODIPY molecule and its chlorinated form. The optimized conformation of dimers is well in alignment with the one provided in the literature. The HOMO LUMO gap of dichloro-derivative is smaller than that of the dimeric aza-BODIPY molecule by 35.0 meV. The predicted HOMO energies of -6.40 and -6.60 eV point out the good stabilities of both compounds. They were reported to demonstrate bathochromic shifts of 40 and 57 nm compared to their monomers substituted by H and Cl, respectively. The intriguing photophysical behaviors of these molecules were investigated by conducting the Tamm-Dancoff density functional theory (TDA-DFT) calculations. The max values emerge from the HOMO-1 -&gt; LUMO+1 (83-86%) transitions, whereas the low energy transitions arise from HOMO -&gt; LUMO (89%). Therefrom predicted ELUMO-&gt;HOMO of the dimeric aza-BODIPY and dichloro-derivative are 1.89 and 1.87 eV, respectively, which are matching well with the reported literature values.
Experiencias en el uso del internet en estudiantes de enfermería de una universidad privada
Authors: Cabrejos Solis Sandra Nevenka , Guerrero Quiroz Elizabeth Soledad , Díaz Manchay Rosa Jeuna 
Published: July 2021

Objetivo: Describir y comprender las experiencias en el uso de internet de los estudiantes de la Escuela de Enfermería del I y II ciclo de una universidad privada de Chiclayo, 2019. Método: Esta investigación fue cualitativa con abordaje descriptivo exploratorio, lo conformaron todos los estudiantes universitarios pertenecientes al I y II ciclo 2019 II de la escuela de enfermería de la Universidad Católica Santo Toribio de Mogrovejo, quienes llevaron todos sus cursos de acuerdo a su plan de estudios, solteros, sus edades oscilaban entre 17-20 años, una población adolescente y joven. El tamaño de la muestra fue de 12 estudiantes regulares de enfermería, y fue determinada por la técnica de saturación y redundancia de datos. Para la obtención de datos se aplicó la entrevista semi-estructurada a profundidad, elaborada por la investigadora y fue validada por juicio de expertos. Los datos se procesaron con análisis de contenido, se guardó los principios éticos y de rigor científico. Resultados principales: Dos categorías: a) Uso de internet como soporte educativo: campus virtual, búsqueda de información y trabajos grupales y b) Uso de internet como medio de comunicación y entretenimiento: riesgos y repercusiones. Conclusión general: Los estudiantes de enfermería ven al internet como una herramienta muy importante en su formación, comunicación y entretenimiento universitario, pero al mismo tiempo vivenciaron repercusiones en su salud (trastornos del patrón del sueño como el insomnio, los ojos rojos y cansados, cansancio físico), como en lo social (ciberbullying).
Descriptores (indicando identificador único): Experiencia (D008016) Internet (D020407), estudiantes de enfermería (D013338).
Aplicación de la fenomenología de Amedeo Giorgi como sustento metodológico
Authors: Martínez Ávila Brenda , Alvarez Aguirre Alicia 
Published: July 2021

El método fenomenológico permite comprender el significado de las experiencias vividas de las personas acerca de un fenómeno en particular a investigar, tiene como interés volver a la esencia misma de las cosas es decir revivir la experiencia acontecida para en base a ello construir o reconstruir el conocimiento, pero ¿cómo se aplica la fenomenología de Amedeo Giorgi como sustento metodológico? Por ello, el objetivo del presente ensayo es explicar la aplicación de la fenomenología de Amedeo Giorgi como sustento metodológico del estudio de las experiencias de vida cotidiana en adolescentes, hijos de padres con consumo dependiente de alcohol. Se concluye, que al buscar las esencias y utilizar lo invariante e invariable del fenómeno particular de estudio, el investigador puede descubrir la experiencia concreta de los participantes y reflexionar sobre las diferentes posibilidades de significados de sus experiencias, es decir, intenta alcanzar lo esencial. El propósito del método de Giorgi es descubrir y articular los significados que el participante experimentó a través del fenómeno que se investiga. Finalmente, aplicar la fenomenología de Amedeo Giorgi como sustento metodológico en el estudio de las experiencias de la vida cotidiana permite comprender la perspectiva singular desde la cual los adolescentes ven el mundo real en el que viven, el cual se contextualiza en un ambiente de consumo dependiente de alcohol de sus padres donde las tipificaciones propias de la vida cotidiana de los actores clarificarán la interpretación que le dan a sus motivos y acciones.

Palabras clave: Fenomenología, metodología, alcoholismo, padres, adolescencia.