bluuebunny/crossref_metadata_2025_split huggingface dataset:
Nanomaterials induce different levels of oxidative stress, depending on the used model system: Comparison of in vitro and in vivo effects
Authors: Karkossa Isabel , Bannuscher Anne , Hellack Bryan , Wohlleben Wendel , Laloy Julie , Stan Miruna S. , Dinischiotu Anca , Wiemann Martin , Luch Andreas , Haase Andrea , von Bergen Martin , Schubert Kristin 
Published: August 2020

Abstract
Background The immense variety and constant development of nanomaterials (NMs) raise the demand for a facilitated risk assessment, for which knowledge on NMs mode of actions (MoAs) is required. For this purpose, a comprehensive data basis is of paramountcy that can be obtained using omics. Furthermore, the establishment of suitable in vitro test systems is indispensable to follow the 3R concept and to master the high number of NMs. In the present study, we aimed at comparing NM effects in vitro and in vivo using a multi-omics approach. We applied an integrated data evaluation strategy based on proteomics and metabolomics to four silica NMs and one titanium dioxide-based NM. For in vitro investigations, alveolar epithelial cells and alveolar macrophages were treated with different doses of NMs, and the results were compared to effects on rat lungs after short-term inhalations and instillations at varying doses with and without a recovery period.Results Since the production of reactive oxygen species (ROS) is described to be a critical biological effect of NMs, and enrichment analyses confirmed oxidative stress as a significant effect upon NM treatment in vitro in the present study, we focused on different levels of oxidative stress. Thus, we found opposite changes for proteins and metabolites that are related to the production of reduced glutathione in alveolar epithelial cells and alveolar macrophages, illustrating that NMs MoAs depend on the used model system. Interestingly, in vivo, pathways related to inflammation were affected to a greater extent than oxidative stress responses. Hence, the assignment of the observed effects to the levels of oxidative stress was different in vitro and in vivo as well. However, the overall classification of “active” and “passive” NMs was consistent in vitro and in vivo.Conclusions The consistent classification indicates both tested cell lines to be suitable for NM toxicity assessment even though the induced levels of oxidative stress strongly depend on the used model systems. Thus, the here presented results highlight that model systems need to be carefully revised to decipher the extent to which they can replace in vivo testing.
Fluid flow exposure promotes Epithelial-to-Mesenchymal Transition and adhesion of breast cancer cells to endothelial cells
Authors: Fuh Kenneth F. , Shepherd Robert D. , Withell Jessica S. , Kooistra Brayden K. , Rinker Kristina D 
Published: August 2020

Abstract
Background: Fluid forces are an integral part of the tumor microenvironment through all phases of development and progression. However, it is not well understood how these forces affect key steps in the progression of breast cancer of Epithelial-to-Mesenchymal Transition (EMT) and adhesion to vascular wall endothelial cells. EMT is associated with the progression of most carcinomas through induction of new transcriptional programs within affected epithelial cells, resulting in cells becoming more motile and adhesive to endothelial cells.Methods: MDA-MB-231, SK-BR-3, BT-474, and MCF-7 cells and normal Human Mammary Epithelial Cells (HMECs) were exposed to fluid flow in a parallel-plate bioreactor system. Changes in gene expression were quantified using microarrays and qPCR, gene-gene interactions were elucidated using network analysis, and key modified genes were examined in clinical datasets. Changes in protein expression of key EMT markers between chemically induced EMT and flow-exposed cells were compared in immunocytochemistry assays. Finally, the ability of flow-stimulated and unstimulated cancer cells to adhere to an endothelial monolayer was evaluated in flow and static adhesion experiments.Results: Fluid flow stimulation resulted in upregulation of EMT inducers and downregulation of repressors. Specifically, Vimentin and Snail were upregulated both at the gene and protein expression levels in flow stimulated HMECs, suggesting progression towards an EMT phenotype. Flow-induced overexpression of a panel of cell adhesion genes was also observed. Network analysis revealed genes involved in cell flow responses including FN1, PLAU, and ALCAM. When evaluated in clinical datasets, overexpression of FN1, PLAU, and ALCAM was observed in patients with most subtypes of breast cancer. We also observed increased adhesion of flow-stimulated breast cancer cells compared to unstimulated controls, suggesting an increased potential to form secondary tumors at metastatic sites. Conclusions: This study shows that prolonged fluid force exposure on the order of 1 Pa promotes EMT and adhesion of breast cancer cells to an endothelial monolayer. Further, identified biomarkers were distinctly expressed in patient populations. A better understanding of how biophysical forces such as shear stress affect cellular processes involved in metastatic progression of breast cancer is important for identifying new molecular markers for disease progression, and for predicting metastatic risk.
The Longitudinal Relationship Between Immune Cell Profiles and Frailty in Patients with Breast Cancer receiving Chemotherapy
Authors: Gilmore Nikesha , Mohile Supriya , Lei Lianlian , Culakova Eva , Mohamed Mostafa , Magnuson Allison , Loh Kah Poh , Maggiore Ronald , Belcher Elizabeth , Conlin Alison , Weiselberg Lora , Ontko Mary , Janelsins Michelle 
Published: August 2020

Abstract
Background: Frailty is associated with an increased risk of chemotherapy toxicity. Cellular markers of inflammation can help identify patients with frailty characteristics. However, the role of cellular markers of inflammation in identifying patients at risk of developing chemotherapy-induced frailty and their clinical utility are not fully understood.Methods: This study was a secondary analysis of a large nationwide cohort study of women with stage I-IIIC breast cancer (n=581, mean age 53.4; range 22-81). Measures were completed pre-chemotherapy (T1; ≤7 days before first cycle), post-chemotherapy (T2; ≤ 1 month after last cycle), and 6 months post-chemotherapy (T3). Frailty was assessed at all three time-points using a modified Fried score consisting of four self-reported measures (weakness, exhaustion, physical activity, and walking speed; 0-4, 1 point for each). Immune cell counts as well as neutrophil to lymphocyte ratio (NLR) and lymphocyte to monocyte ratio (LMR) were obtained at T1 and T2 time-points. Separate linear regressions were used to evaluate the associations of: 1) cell counts at T1 with frailty at T1, T2, and T3 and 2) change in cell counts (T2-T1) with frailty at T2 and T3. We controlled for relevant covariates and frailty at the T1 time-point. Results: From T1 to T2, the mean frailty score increased (1.3 vs 2.0; p<0.01) and returned to T1 levels by the T3 time-point (1.3 vs 1.3; p=0.85). At the T1 time-point, there was a positive association between cellular markers of inflammation and frailty: WBC (β=0.04; p<0.05), neutrophils (β=0.04; p<0.05), and NLR (β=0.04; p<0.01). From T1 to T2, a greater increase in cellular markers of inflammation was associated with frailty at T2 (WBC: β=0.02; p<0.05, neutrophils: β=0.03; p<0.05, NLR: β=0.03; p<0.01). These associations remained significant after controlling for the receipt of growth factors with chemotherapy. Conclusions: In patients with breast cancer undergoing chemotherapy, cellular markers of inflammation are associated with frailty. Immune cell counts may help clinicians identify patients at risk of frailty during chemotherapy. Trial Registration: ClinicalTrials.gov Identifier: NCT01382082
Subcutaneous Trastuzumab with Pertuzumab and Docetaxel in HER2-Positive Metastatic Breast Cancer: Final Analysis of MetaPHER, A Phase 3b Single-Arm Safety Study
Authors: Kümmel Sherko , Tondini Carlo Alberto , Abraham Jacinta , Nowecki Zbigniew , Itrych Bartosz , Hitre Erika , Karaszewska Bogusława , Juárez-Ramiro Alejandro , Morales-Vásquez Flavia , García Jose Manuel Pérez , Cardona-Huerta Servando , Monturus Estefania , Sequi Marco , Restuccia Eleonora , Benyunes Mark , Martín Miguel 
Published: August 2020

Abstract
BACKGROUND Intravenous trastuzumab, pertuzumab, and docetaxel is first-line standard of care for patients with HER2-positive metastatic breast cancer. Subcutaneous trastuzumab plus intravenous pertuzumab and chemotherapy has shown similar safety and tolerability to intravenous trastuzumab in patients with HER2-positive early and metastatic breast cancer; however, in the metastatic setting, this has yet to be shown globally.METHODS In this open-label, single-arm, multicenter phase 3b study, eligible patients were ≥18 years old with histologically/cytologically confirmed previously untreated HER2-positive metastatic breast cancer. All patients received ≥1 dose of subcutaneous trastuzumab (fixed-dose 600 mg) plus intravenous pertuzumab (loading dose: 840 mg/kg; maintenance dose: 420 mg/kg) and docetaxel (≥6 cycles; initial dose 75 mg/m2) every 3 weeks. The primary objective was safety and tolerability; secondary objectives included efficacy.RESULTS At clinical cutoff, 276 patients had completed the study; median duration of follow-up was 27 months. The most common any-grade adverse events were diarrhea, alopecia, and asthenia. The most common grade ≥3 adverse events were neutropenia, febrile neutropenia, and hypertension. There were no cardiac deaths and mean left ventricular ejection fraction was stable over time. Median investigator-assessed progression-free survival was 18.7 months; objective response rate was 75.6%.CONCLUSIONS Efficacy/safety results of subcutaneous trastuzumab plus intravenous pertuzumab and docetaxel in metastatic breast cancer are consistent with historical evidence of intravenous trastuzumab. These findings further support the body of evidence indicating that subcutaneous administration does not affect the safety and efficacy profile of trastuzumab in HER2-positive breast cancer. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT02402712 (date of registration: 30th March 2015)
Tamoxifen Suppresses Brain Metastasis of Estrogen Receptor-deficient Breast Cancer by Skewing Microglia Polarization and Enhancing Their Immune Functions
Authors: Wu Shih-Ying , Sharma Sambad , Wu Kerui , Tyagi Abhishek , Zhao Dan , Deshpande Ravindra Pramod , Watabe Kounosuke 
Published: August 2020

Abstract
Background: Brain metastasis of breast cancer exhibits exceedingly poor prognosis, and both triple negative and Her2+ subtypes have the highest incidence of brain metastasis. Although estrogen blockers are considered to be ineffective for their treatment, recent evidences indicate that estrogen blockade using tamoxifen showed certain efficacy. However, how estrogen affects brain metastasis of triple negative breast cancer (TNBC) remains elusive. Methods: To examine the effect of estrogen on brain metastasis progression, nude mice were implanted with brain metastatic cells and treated with either estrogen supplement, tamoxifen or ovariectomy for estrogen depletion. For clinical validation study, brain metastasis specimens from pre- and post-menopause breast cancer patients were examined for microglia polarization by immunohistochemistry. To examine the estrogen-induced M2 microglia polarization, microglia cells were treated with estrogen and the M1/M2 microglia polarization was detected by qRT-PCR and FACS. The estrogen receptor-deficient brain metastatic cells, SkBrM and 231BrM, were treated with conditioned medium (CM) derived from microglia that were treated with estrogen in the presence or absence of tamoxifen. The effect of microglia-derived CMs on tumor cells was examined by colony formation assay and sphere forming ability. Results: We found that M2 microglia were abundantly infiltrated in brain metastasis of pre-menopausal breast cancer patients. A similar observation was made in vivo, when we treated mice systemically with estrogen. Blocking of estrogen signaling either by tamoxifen treatment or surgical resection of mice ovaries suppressed M2 microglial polarization and decreased the secretion of C-C motif chemokine ligand 5, resulting in suppression of brain metastasis. The estrogen modulation also suppressed stemness in TNBC cells in vitro. Importantly, estrogen enhanced the expression of signal regulatory protein α on microglia and restricted their phagocytic ability. Conclusions: Our results indicate that estrogen promotes brain metastasis by skewing polarity of M2 microglia and inhibiting their phagocytic ability, while tamoxifen suppresses brain metastasis by blocking the M2 polarization of microglia and increasing their anti-tumor phagocytic ability. Our results also highlight a potential therapeutic utility of tamoxifen for treating brain metastasis of hormone receptor deficient breast cancer.
Manifestasi Teologi Tanah Hassan Hanafi Dalam Gerakan Reclaiming Petani Di Rotorejo-Kruwuk Blitar
Authors: Afifudin Ridho 
Published: August 2020

Abstract
This paper discusses the movement of farmer groups in Blitar in fighting for their rights to plantation land. The land is the company's land that has expired its contract (ex-HGU), so based on government regulations and existing laws, the position of the land may be claimed by residents. But the struggle of the farmers was not as smooth as expected. Various upheaval arose in the process. From this problem, the author sees this problem from the perspective of Hassan Hanafi’s concept of theology. Hanafi explained how human faith became the spirit of the movement to fight for justice. There are two principles stated; First, the principle of needs and benefits, is who most needs access to the land along with the large benefits that will be received. Second, the principle of agreement and understanding; This principle concerns the process of negotiation (deliberation) between the two parties, especially in terms of compensation (ta'widh) if there is a party harmed.
Keywords: Teologi, Hassan Hanafi, Gerakan Petani.

Abstrak
Artikel ini membahas pergerakan kelompok tani di Blitar dalam memperjuangkan hak mereka atas tanah perkebunan. Tanah tersebut adalah tanah perusahaan yang telah habis masa kontraknya (ex-HGU), jadi berdasarkan peraturan pemerintah dan undang-undang yang ada, posisi tanah tersebut dapat diklaim oleh penduduk. Namun perjuangan para petani itu tidak semulus yang diharapkan. Berbagai pergolakan muncul dalam prosesnya. Dari masalah ini, penulis melihat masalah ini dalam perspektif konsep teologi Hassan Hanafi. Seperti yang Hanafi jelaskan tentang bagaimana iman manusia menjadi semangat gerakan untuk memperjuangkan keadilan. Ada dua prinsip yang dinyatakan; Pertama, prinsip kebutuhan dan manfaat, adalah siapa yang paling membutuhkan akses ke tanah bersama dengan manfaat besar yang akan diterima. Kedua, prinsip kesepakatan dan pemahaman; Prinsip ini menyangkut proses negosiasi (musyawarah) antara kedua pihak, terutama dalam hal kompensasi (ta'widh) jika ada pihak yang dirugikan.
Kata Kunci: Teologi, Hassan Hanafi, Gerakan Petani.
Eupatilin Inhibits the Proliferation and Migration of Prostate Cancer Cells through Modulation of PTEN and NF-κB Signaling
Authors: Serttas Riza , Koroglu Cagla , Erdogan Suat 
Published: August 2020

Background:
Despite advances in the treatment of prostate cancer, side effects and the risks of developing
drug resistance require new therapeutic agents. Eupatilin is a secondary metabolite of Artemisia asiatica
and has shown potential anti-tumor activity in some cancers, but its potential in prostate cancer treatment has
not yet been evaluated.

Objective:
The aim of the study was to investigate the effectiveness of eupatilin on prostate cancer cell proliferation
and migration.

Methods:
Human prostate cancer PC3 and LNCaP cells were exposed to eupatilin and its efficacy on cell survival
was determined by the MTT test. Apoptosis and cell cycle phases were evaluated by an image-based cytometer.
Cell migration and invasion were evaluated by wound healing and matrigel migration assays; the expression
of mRNA and protein was assessed by RT-qPCR and Western blot, respectively.

Results:
Eupatilin time- and dose-dependently reduced the viability of prostate cancer cells. Exposure of PC3
cells to 12.5μM-50μM eupatilin resulted in apoptosis by upregulating the expression of caspase 3, Bax and
cytochrome c. Annexin V assessment also confirmed that eupatilin causes apoptosis. The treatment significantly
upregulated the mRNA expression of p53, p21, and p27, causing cell cycle arrest in the G1 phase. Administration
of eupatilin inhibited migration and invasion of the cells by downregulating the expression of Twist, Slug
and MMP-2, -7. In addition, the agent increased protein expression of tumor suppressor PTEN, while transcription
factor NF-κB expression was reduced.

Conclusion:
Eupatilin strongly prevents the proliferation of prostate cancer cells, and suppresses migration and
invasion. Due to its therapeutic potential, the clinical use of eupatilin in prostate cancer should also be supported
by in vivo studies.
Leaf Image Classification with the Aid of Transfer Learning: A Deep Learning Approach
Authors: Dammavalam Srinivasa Rao , Challagundla Ramesh Babu , Kiran Vangipuram Sravan , Nuvvusetty Rajasekhar , Baru Lalith Bharadwaj , Boddeda Rohit , Kanumolu Sai Vardhan 
Published: August 2020

Background:
Crop diseases are a primary hazard to nutrient safety, which proves to be a
serious problem in many places in the world due to the unavailability of essential aid. Typically agriculturalists
or specialists perceive the plants with a naked eye for detection and identification of
an illness. Machine vision models, in specific Convolutional Neural Networks (CNNs) have directed
an impact in feature extraction to a greater extent. Since 2015, numerous solicitations for the
automatic classification and recognition of crop illnesses have been established.

Methods:
In this paper, we proposed, analyzed, and assessed various state-of-the-art models proposed
over a decade. These models are pre-trained with the finest parameters where we modeled a
design-oriented method with numerous leaf-images and classified them into infection and healthy
class for each type of leaf independently.

Results:
Through our examination, we concluded that VGG models stand-alone with many cited
prototypes and give on par results. As declared, these VGG models (VGG16 and VGG19) are utilized
for feature extraction, and further, we augmented a set of dense layers and train them consequently
for classification. The performances of various machine vision prototypes were pictorially
perceived and their sophisticated architecture is not only capable of extracting detailed features but
also repressed many loop-holes. The performance is assessed and computed for several types of leaf
images and the accuracy scores attained were more than 97.5% for VGG16 and 96.72% for VGG19.

Conclusion:
AUC-ROC curves were portrayed to illustrate its inspiration in defining an accurate
classification where VGG16 and VGG19 have at least 96.6% and 95% area under the curve (AUC)
which resembles their robustness.
Views of Implementers and Nonimplementers of Internet-Administered Cognitive Behavioral Therapy for Depression and Anxiety: Survey of Primary Care Decision Makers in Sweden
Authors: Brantnell Anders , Woodford Joanne , Baraldi Enrico , van Achterberg Theo , von Essen Louise 
Published: August 2020

Background
Internet-administered cognitive behavioral therapy (ICBT) has been demonstrated to be an effective intervention for adults with depression and/or anxiety and is recommended in national guidelines for provision within Swedish primary care. However, the number and type of organizations that have implemented ICBT within primary care in Sweden is currently unclear. Further, there is a lack of knowledge concerning barriers and facilitators to ICBT implementation.

Objective
The two primary objectives were to identify and describe primary care organizations providing ICBT in Sweden and compare decision makers’ (ie, directors of primary care organizations) views on barriers and facilitators to implementation of ICBT among ICBT implementers (ie, organizations that offered ICBT) and nonimplementers (ie, organizations that did not offer ICBT).

Methods
An online survey based on a checklist for identifying barriers and facilitators to implementation was developed and made accessible to decision makers from all primary care organizations in Sweden. The survey consisted of background questions (eg, provision of ICBT and number of persons working with ICBT) and barriers and facilitators relating to the following categories: users, therapists, ICBT programs, organizations, and wider society.

Results
The participation rate was 35.75% (404/1130). The majority (250/404, 61.8%) of participants were health care center directors and had backgrounds in nursing. Altogether, 89.8% (363/404) of the participating organizations provided CBT. A minority (83/404, 20.5%) of organizations offered ICBT. Most professionals delivering ICBT were psychologists (67/83, 80%) and social workers (31/83, 37%). The majority (61/83, 73%) of organizations had 1 to 2 persons delivering ICBT interventions. The number of patients treated with ICBT during the last 12 months was 1 to 10 in 65% (54/83) of the organizations, ranging between 1 and 400 treated patients across the whole sample. There were 9 significant (P<.05) differences out of 37 possible between implementers and nonimplementers. For example, more implementers (48/51, 94%) than nonimplementers (107/139, 76.9%) perceived few technical problems (P<.001), and more implementers (53/77, 68%) than nonimplementers (103/215, 47.9%) considered that their organization has resources to offer ICBT programs (P<.001).

Conclusions
Despite research demonstrating the effectiveness of ICBT for depression and anxiety and national guidelines recommending its use, ICBT is implemented in few primary care organizations in Sweden. Several interesting differences between implementers and nonimplementers were identified, which may help inform interventions focusing on facilitating the implementation of ICBT.
PREDIKSI KONDISI FINANCIAL DISTRESS PADA PERUSAHAAN MANUFAKTUR PERUSAHAAN DI BURSA EFEK INDONESIA
Authors: Gandi Surya , Damayanti Damayanti , Supriyanto Supriyanto 
Published: August 2020

Being aware the signal of financial distress conditions is important because in the worst case scenario the company can be forced in to liquidation. This condition can be predicted using model that have been developed by many researchers. The purpose of this research is analyze and describe the effects of current asset to current liability, debt to total asset, total asset turnover, and net income to equity in predicting the condition of financial distress in manufacturing companies listed in Indonesian Stock Exchange in year 2012-2017. The data analiysis method is logit regression. The resecarch sample used purposive sampling tecnique. The result of wald test (partial) showed that current asset to current liability, debt to total asset and total asset turnover that have significant effects to predict the condition of financial distress in company, whilst net income to equity not significant to predict the condition of financial distress in the company. The result of G2/likehood showed that current asset liability, debt to total asset, total asset turnover and net income to equity simultaneously have significant influence to predict the condition of financial distress in company. Value of Mc fadden R-squared (R2) showed the relation among the variabels is in a very strong category.