bluuebunny/crossref_metadata_2025_split huggingface dataset:
CDK12 inhibition enhances sensitivity of HER2+ breast cancers to HER2-TKI via suppressing PI3K/AKT
Authors: Li Hui , Wang Jinsong , Yi Zongbi , Li Chunxiao , Wang Haijuan , Zhang Jingyao , Wang Ting , Nan Peng , Lin Feng , Xu Dongkui , Zhan Qimin , Qian Haili , Ma Fei 
Published: May 2020

Abstract
Background : While anti-HER2 tyrosine kinase inhibitors (TKIs) have radically prolonged survival and improved prognosis in HER2-positive breast cancer patients, resistance to these therapies is a constant obstacle leading to TKIs treatment failure and tumor progression.Methods : To develop new strategies to enhance TKIs efficiency by combining synergistic gene targets, we performed panel library screening using CRISPR/Cas9 knockout technique based on data mining across TCGA datasets and verified the candidate target in pre-clinical models and breast cancer high-throughput sequencing datasets.Results : We identified that CDK12, co-amplified with HER2 in a high frequency, is powerful to sensitize or re-sensitize HER2-positive breast cancer to anti-HER2 TKIs lapatinib, evidenced by patient-derived organoids (PDO) in vitro and cell-derived xenograft (CDX) or patient-derived xenograft (PDX) in vivo. Exploring mechanisms, we found that inhibition of CDK12 attenuated PI3K/AKT signal, which usually serves as an oncogenic driver and is reactivated when HER2-positive breast cancers develop resistance to lapatinib. Combining CDK12 inhibition exerted additional suppression on p-AKT activation induced by anti-HER2 TKIs lapatinib treatment. Clinically, via DNA sequencing data for tumor tissue and peripheral blood ctDNA, we found that HER2-positive breast cancer patients with CDK12 amplification responded more insensitively to anti-HER2 treatment than those without accompanying CDK12 amplification by harboring a markedly shortened progression free survival (PFS) (median PFS: 4.3 months verse 6.9 months; HR 2.26 [95% CI 1.32-3.86]; P=0.0028).Conclusions : Dual inhibition of HER2/CDK12 will prominently benefit the outcomes of HER2-positive breast cancer patients by sensitizing or re-sensitizing the tumors to anti-HER2 TKIs treatment.
Investigating occupational stress of disaster and emergency medical management center 115 and the role of demographic variables
Authors: lebni Javad Yoosefi , Gheshlaghi Parvin Abdi , Toghroli Razie , Garosi Vahid Hatami , Abbas Jaffar , Kalhori Reza Pourmirza , Salahshoor Mohammad Reza , Kianipour Neda , Tharwani Munira , ziapour arash 
Published: May 2020

Abstract
Background: The first and one of the most important chains of providing care to patients is prehospital emergency medical services. The critical crisis put the Personnel employed in this sector at risk due to occupational stress confronted during on- job and at service. This can adversely affect the health of the personnel and the quality of services, which are being provided to patients. Therefore, the present study has been conducted to investigate the occupational stress of the personnel confronting disaster and emergency medical management center 115 along with the role of demographic variables in 2019.Methods: This is a descriptive-analytical study. 200 medical emergency personnel of Kermanshah province were selected through stratified sampling and according to inclusion criteria. A two-part questionnaire including demographic information and HSE standard questionnaire were used for collecting data. Finally, descriptive and inferential statistics (t-test and one-way ANOVA) were used for data analysis. Significance level was considered P<0.05. Results: The mean score of total occupational stress was 3.41±0.26. The highest and the lowest stress levels related to the role dimensions was calculated (4.34±0.35) and changes (2.72±0.86). It was evident through findings that there was a significant relationship between stress level with age, marital status, educational level, type of base of work place and hours of work per month, while there was no significant relationship between type of employment and work experience with stress level. Conclusion: Emergency medical personnel experience a high level of occupational stress in terms of handing of patients. Senior managers can apply the results for conducting similar studies, Moreover, this study can be useful to devise measures to reduce the experience of employees' stress.
Mental health among COVID-19 survivors and healthcare workers exposed to COVID-19 in Wuhan, China: a cross-sectional study
Authors: Chen Bin , Wang Yan , Yang Ting , Li Cheng , Sun Zhiling 
Published: May 2020

Abstract
Then novel coronavirus disease (COVID-19) epidemic was considered to be the worst and complex virus outbreak, which caused 56,985 deaths as of April 22, 2020 already. The epidemic infectious may cause mental health crisis. Meanwhile, little is known about the specific psychological status of the COVID-19 survivors and healthcare workers. This cross-sectional study surveyed the mental health among 20 COVID-19 survivors, 54 nurses, and 24 hygienists in Wuhan, China and analyze the possible impact factors using the Symptom Check List 90 - Revised (SCL90-R) questionnaire. 3 indices and 9 dimensions were compared among job, education level, gender, age, marriage classification. This study found that mental distress among participants was not very serious in general. The survivors presented a highest score, then the hygienists, and the lowest in nurses. Low-educated and women showed significant increase. No significant difference was noted in age and marriage classification. Our study indicated that the survivors need psychological support immediately. Meanwhile, healthcare workers warrant more attention, especially low-educated and women. Comprehensive emergency response plan was warranted.
FTO demethylates m6A modifications in HOXB13 mRNA and promotes endometrial cancer metastasis by activating the WNT signaling pathway
Authors: Zhang Lin , Wan Yicong , Zhang Zihan , Jiang Yi , Lang Jinghe , Cheng Wenjun , Zhu Lan 
Published: May 2020

Abstract
Background Abnormal FTO expression causes faulty m6A modifications in mRNA and affects tumor progression. However, the expression and function of FTO in endometrial cancer (EC) and the genes regulated by FTO remain unclear.Methods qPCR detected the FTO expression level in EC tissues, and IHC staining determined the FTO protein expression in tissue arrays. FTO was stably overexpressed or knocked down in EC cell lines by lentiviruses. The biological roles of FTO in cancer cell metastasis and invasion were evaluated by wound-healing, Transwell assays and mouse intra-abdominal implantation models. mRNA-seq, RIP-seq, and MeRIP-seq were combined to comprehensively map the genes regulated by FTO. RNA pull-down, dual-luciferase reporter and RNA stability experiments confirmed that YTHDF2 regulates the metabolism of HOXB13 mRNA via m6A. Western blot analysis confirmed that HOXB13 regulates EC cell metastasis and invasion through the WNT signaling pathway.Results FTO is more highly expressed in metastatic EC and can promote tumor metastasis and invasion in vivo and in vitro. By removing the m6A modification in the 3'UTR region of HOXB13, FTO abolishes m6A recognition by YTHDF2 and promotes the stability of HOXB13 mRNA and protein expression. High HOXB13 expression activates the WNT signaling pathway, promotes c-myc, snail, MMP2, MMP7, and MMP9 expression, and inhibits E-cadherin expression, leading to tumor metastasis and invasion.Conclusions FTO promotes HOXB13 expression through m6A, activates the WNT signaling pathway, and promotes EC invasion and metastasis. FTO is a new potential target for the treatment of tumor metastasis.
Trans-Sphenoidal Surgery in Prolactin Secreting Pituitary Tumors: A Long-Term Referral Center Experience.
Authors: Mattogno Pier Paolo , D’alessandris Quintino Giorgio , Chiloiro Sabrina , Bianchi Antonio , Giampietro Antonella , Marinis Laura De , Olivi Alessandro , Anile Carmelo , Lauretti Liverana 
Published: May 2020

Abstract
Backgrounds: Prolactin secreting pituitary tumors (PRL-omas) represent a unique challenge for endocrinologists and neurosurgeons. Considering recent innovations in surgical, we aimed to investigate the best management for PRL-omas. Methods: A retrospective, cross-sectional and monocentric study was designed. Consecutive patients affected for PRL-omas were enrolled if treated with first line treatment with dopamine-agonist (DA) or trans-sphenoidal surgery (TSS). Patients carried giant PRL-omas and those with a follow-up < 12 months were excluded. Results: 259 patients were enrolled. The first treatment was DA for 140 patients and TSS for 119 cases. 146 of 249 patients (58.6%) needed a second therapy. Mean follow up was 102.2 months (12-438 months). Surgery highly impacted on the cure rate, in particular in females (p=0.0021) and in micro- PRL-omas (p=0.0020). Considering multivariate analysis, female gender and surgical treatment in the course of clinical history were the only independent positive predictors of cure at the end of 5 years follow-up (p=0.0016, p=0.0005). The evaluation of serum prolactin (24 hours after TSS) revealed that 86.4% of patients with post-operative PRL≤10 ng/ml resulted cured at the end of follow-up (p< 0.0001). Conclusion: According to our experience, surgery allows a higher cure rate of PRL-omas, in particular in females with micro-PRL-omas, with a good safety profile. TSS for PRL-oma should be considered as first line therapy, in the management of patients, during the multidisciplinary evaluation, in center of reference for pituitary diseases, in order guarantee a valid surgical outcome and a safety profile.
LncRNA KCNQ1OT1 is a Key Factor in the Reversal Effect of Curcumin on Cisplatin Resistance in the Colorectal Cancer Cells
Authors: Zheng Zhi-hai , You He-yi , Feng Yu-jie , Zhang Zhong-tao 
Published: May 2020

Abstract
Context: The development of cisplatin resistance is a common cause of cancer recurrence in colorectal cancer (CRC). Long non-coding RNA KCNQ1OT1 has been proven to exert its oncogenic function in multiple cancers. Curcumin is a natural phenolic that could effectively suppress cisplatin resistance in CRC.Objective: To expound the role of KCNQ1OT1 in cisplatin resistance in CRC cells and whether KCNQ1OT1 participates in the reversal effect of curcumin on cisplatin resistance in CRC. Methods: Cell proliferation and apoptosis were evaluated by CCK-8 assay and flow cytometry assay, respectively. The interplay between KCNQ1OT1 and miR-497 was determined using RNA pull-down assay and dual-luciferase reporter gene assay. The combination of B-cell lymphoma 2 (Bcl-2) and miR-497 was confirmed using dual-luciferase reporter gene assay. Results: Compared with CRC cell line HCT8, the cisplatin-resistant CRC cell line HCT8/DDP exhibited a higher KCNQ1OT1 expression. Functionally, the silence of KCNQ1OT1 suppressed proliferation and promoted apoptosis in HCT8/DDP cells. KCNQ1OT1 could act as a sponge of miR-497 and removed the suppressive effect of miR-497 on Bcl-2 expression. Curcumin treatment suppressed proliferation and promote apoptosis in HCT8/DDP cells. While KCNQ1OT1 overexpression removed the effect of curcumin on HCT8/DDP cells via miR-497/ Bcl-2 axis. Finally, the in vivo experiments confirmed that the ectopic expression of KCNQ1OT1 reversed the suppressive effect of curcumin on the growth of cisplatin-resistant CRC cells.Conclusion: KCNQ1OT1 promoted cisplatin resistance in CRC cells via the miR-497/Bcl-2 axis. Administration of curcumin could effectively down-regulate KCNQ1OT1 expression, thus reversing cisplatin resistance in CRC cells.
Modeling and Simulation to Improve the Efficiency of Transportation Systems: A Tool for Decision Support
Authors: Suryani Erma , Hendrawan Rully Agus , Adipraja Philip Faster Eka , Indraswari Rarasmaya , Ahyudanari Ervina , Jauhari Achmad , Prambayanto Prasetyo 
Published: May 2020

Abstract
This paper addresses problem solving and complex decision making in the management of transportation operations under environmental dynamics through the use of models and scenarios. A system dynamics simulation was used to model and analyze the efficiency of transportation systems as a tool for decision support to improve efficiency. Transportation systems are complex because they involve a number of different stakeholders, resulting in feedback with different time lags between the responses of all entities. Data and information were collected from the Transportation Department of Surabaya city. Several scenarios to improve the efficiency of transportation systems were developed by modifying the structure and parameters of the model. Several factors influence the efficiency of transportation system: traffic network, conventional roadway, accessibility based transport planning, multi modal transport, planning efficiency, and resources efficient modes (economic category). By implementing a number of strategies (such as the improvement of planning efficiency; multimodal transport development; route-based performance improvement), transportation system efficiency in Surabaya was predicted to be improved from 56% in 2019 to 66% in 2040. The novel contributions of this research are: formulating relationships among several variables, modeling dynamic behavior of transportation system efficiency, and building scenario models to improve transportation operation efficiency. This research contributes to the literature by investigating these relationships through the use of models and experimental scenarios.
Transmission Dynamics of COVID-19 in Bangladesh- A Compartmental Modeling Approach&nbsp;
Authors: Muka Abul Mukid Md. , Sannyal Mridul 
Published: May 2020

Abstract
The coronavirus disease (COVID-19) was first identiﬁed in Bangldesh, on March 8, 2020. As of May 15, there are 20065 confirmed COVID-19 cases, including 3882 patients who have recovered and 298 related deaths. The objective of this study is to examine the transmission dynamics of COVID-19 and predict the growth of the infection in Bangladesh using the publicly available data though a mathematical model. The suscected-exposed-infectious-recoverd-dead (SEIRD) model is employed to describe the dynamics based on the kinematic parameters fitted on the data for the outbreak in Bangladesh up to May 15. The expression of basic reproduction number using the next generating matrix is derived and estimated. The kinematic parameters that describe transmission rate (0.045), recovery rate (0.03) and death rate (0.01) seems to be lower, respective of other countries. Based on the official counts for confirmed cases, the simulations suggest that the cumulative number of active infected follows an exponential trend. The mean reproduction number 2.25 (95% CI: 1.90-2.40) and transmission trends clearly indicates the outbreak of COVID-19 in Bangladesh. There is now breakneck concern regarding the capacity to respond to needs of infected patients effectively and to prevent this pandemic from further spreading in Bangladesh, one of the densest countries in the world.
Identification of phytochemical inhibitors against main protease of COVID-19 using molecular modeling approaches
Authors: Kumar Anuj , Choudhir Gourav , Shukla Sanjeev Kumar , Sharma Mansi , Tyagi Pankaj , Bhushan Arvind , Rathore Madhu 
Published: May 2020

Abstract
Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is a novel corona virus that causes corona virus disease 2019 (COVID-19). The COVID-19 rapidly spread across the nations with high mortality rate even as very little is known to contain the virus at present. In the current study, we report novel natural metabolites namely, ursolic acid, carvacrol and oleanolic acid as the potential inhibitors against main protease (Mpro) of COVID-19 by using integrated molecular modeling approaches. From a combination of molecular docking and molecular dynamic (MD) simulations, we found three ligands bound to protease during 50 ns of MD simulations. Furthermore, the molecular mechanic/generalized/Born/Poisson-Boltzmann surface area (MM/G/P/BSA) free energy calculations showed that these chemical molecules have stable and favourable energies causing strong binding with binding site of Mpro protein. All these three molecules, namely, ursolic acid, carvacrol and oleanolic acid, have passed the ADME (Absorption, Distribution, Metabolism, and Excretion) property as well as Lipinski’s rule of five. The study provides a basic foundation and suggests that the three phytochemicals, viz. ursolic acid, carvacrol and oleanolic acid could serve as potential inhibitors in regulating the Mpro protein's function and controlling viral replication.
The Effect of Oxidative Stress and Antioxidant Therapies on Pancreatic β-cell Dysfunction: Results from in Vitro and in Vivo Studies
Authors: Anastasiou Ioanna A. , Eleftheriadou Ioanna , Tentolouris Anastasios , Koliaki Chrysi , Kosta Ourania A. , Tentolouris Nikolaos 
Published: May 2020

Background:
Oxidative stress is a hallmark of many diseases. A growing body of
evidence suggests that hyperglycemia-induced oxidative stress plays an important role in pancreatic
β-cells dysfunction and apoptosis, as well as in the development and progression of
diabetic complications. Considering the vulnerability of pancreatic β-cells to oxidative damage,
the induction of endogenous antioxidant enzymes or exogenous antioxidant administration
has been proposed to protect pancreatic β-cells from damage.

Objectives:
The present review aims to provide evidence of the effect of oxidative stress and
antioxidant therapies on pancreatic β-cell function, based on in vitro and in vivo studies.

Methods:
The MEDLINE and EMBASE databases were searched to retrieve available data.

Results:
Due to poor endogenous antioxidant mechanisms, pancreatic β-cells are extremely
sensitive to Reactive Oxygen Species (ROS). Many natural extracts have been tested in vitro
in pancreatic β-cell lines in terms of their antioxidant and diabetes mellitus ameliorating effects,
and the majority of them have shown a dose-dependent protective role. On the other
hand, there is relatively limited evidence regarding the in vitro antioxidant effects of antidiabetic
drugs on pancreatic β -cells. Concerning in vivo studies, several natural extracts have
shown beneficial effects in the setting of diabetes by decreasing blood glucose and lipid levels,
increasing insulin sensitivity, and by up-regulating intrinsic antioxidant enzyme activity.
However, there is limited evidence obtained from in vivo studies regarding antidiabetic drugs.

Conclusion:
Antioxidants hold promise for developing strategies aimed at the prevention or
treatment of diabetes mellitus associated with pancreatic β-cells dysfunction, as supported by
in vitro and in vivo studies. However, more in vitro studies are required for drugs.
Performance Evaluation of Docking Programs- Glide, GOLD, AutoDock & SurflexDock, Using Free Energy Perturbation Reference Data: A Case Study of Fructose-1, 6-bisphosphatase-AMP Analogs
Authors: Reddy K. Kumar , Rathore R.S. , Srujana P. , Burri R.R. , Reddy C. Ravikumar , Sumakanth M. , Reddanna Pallu , Reddy M. Rami 
Published: May 2020

Background:
The accurate ranking of analogs of lead molecules with respect to their estimated
binding free energies to drug targets remains highly challenging in molecular docking due to
small relative differences in their free energy values.

Methods:
Free energy perturbation (FEP) method, which provides the most accurate relative binding
free energy values were earlier used to calculate free energies of many ligands for several important
drug targets including Fructose-1,6-BisphosPhatase (FBPase). The availability of abundant structural
and experimental binding affinity data for FBPase inhibitors provided an ideal system to evaluate four
widely used docking programs, AutoDock, Glide, GOLD and SurflexDock, distinct from earlier comparative
evaluation studies.

Results:
The analyses suggested that, considering various parameters such as docking pose, scoring
and ranking accuracy, sensitivity analysis and newly introduced relative ranking score, Glide provided
reasonably consistent results in all respects for the system studied in the present work. Whereas GOLD
and AutoDock also demonstrated better performance, AutoDock results were found to be significantly
superior in terms of scoring accuracy compared to the rest.

Conclusion:
Present analysis serves as a useful guide for researchers working in the field of lead optimization
and for developers in upgradation of the docking programs.
Procesos legales y tributarios de las mipymes del sector de confecciones de la ciudad de Ocaña
Authors: Quintero-Quintero Wilder , Peñaranda-Peñaranda Marta Milena , Rodríguez-Castilla Magda Mildred 
Published: May 2020

Las Mipymes, representan alrededor del 90% de las empresas existentes a nivel global, emplean el 50% de la mano de obra y participan en la creación del 50% de PIB mundial (Valdés & Sánchez, 2012), de igual manera según el Diario Económico (Portafolio, 2017), en Colombia, el 99,5% de las unidades de explotación económicas son Mipymes, lo que las convierte en el principal cimiento de la actividad productiva nacional; Así como también la Revista (Dinero, 2017) establece que “hoy en día las Mipymes generan el 80% del empleo en el país, lo que demuestra la importancia de trabajar por el desarrollo de estas empresas”. En la ciudad de Ocaña y su área de influencia las Microempresas y las pequeñas y medianas empresas “Mipymes” juegan un papel importante puesto que se constituye en la base de la economía local. Es así, como el sector empresarial de la ciudad de Ocaña Norte de Santander está constituido por 3.358 establecimientos de comercio, donde pertenece el sector de las confecciones el cual está constituido por “Mipymes” quienes desarrollan dentro de su objeto social la elaboración de prendas de vestir para dama, caballeros y niños, estas empresas en gran proporción no se encuentran legalmente constituidas como sociedades, perteneciendo a la informalidad. Teniendo en cuenta lo expuesto anteriormente el comerciante del sector de confecciones de la Ciudad de Ocaña Norte de Santander no tienen la cultura de la organización y control de las actividades que realizan, por esta razón no cuentan con estados financieros que les permitan conocer la realidad económica de sus actividades.
Medición de emisiones atmosféricas en hornos a cielo abierto en el municipio de Ocaña, Norte de Santander
Authors: Guerrero-Gómez Gustavo , Espinel-Blanco Edwin , Flórez-Solano Eder Norberto 
Published: May 2020

Se hizo una relación de las empresas ladrilleras dedicadas a la producción de materiales cerámicos en el municipio de Ocaña, identificando tipo de horno, capacidad y producción. Luego se seleccionó una muestra de siete empresas ladrilleras, a las que se les practicó un muestreo isocinético donde se determinó la concentración de emisiones reguladas por la resolución 909 de junio de 2008 (porcentajes de oxígeno, monóxido de carbono, dióxido de carbono y óxido de nitrógeno),finalmente se hace un análisis del cumplimiento de los requisitos establecidos en la normativa ambiental vigente para emisión por fuentes fijas en las ladrilleras a los hornos en mención ,de lo que se establece que las empresas seleccionadas cumplen con los requisitos establecidos en la normatividad ambiental Colombiana.