bluuebunny/crossref_metadata_2025_split huggingface dataset:
Association between menopausal hormone therapy, mammographic density and breast cancer risk: results from the E3N cohort study
Authors: Fornili Marco , Perduca Vittorio , Fournier Agnès , Jérolon Allan , Boutron-Ruault Marie Christine , Maskarinec Gertraud , Severi Gianluca , Baglietto Laura 
Published: August 2020

Abstract
BACKGROUND: Menopausal hormone therapy (MHT) is a risk factor for breast cancer (BC). Evidence suggests that its effect on BC risk could be partly mediated by mammographic density. The aim of this study is to investigate the relationship between MHT, mammographic density and BC risk using data from a prospective study.METHODS: The data analyzed refer to a case-control study nested into the French cohort E3N and include 453 cases and 453 matched controls. A quantitative measure of mammographic density, a detailed history of MHT use during follow-up and information on potential confounders were available for all women. The association of mammographic density with MHT duration and time since last use was evaluated by linear regression models. Mediation modelling techniques were applied to estimate under the hypothesis of a causal model the proportion of the effect of MHT on BC risk mediated by percent mammographic density for BC overall and by ER/PR status.RESULTS: Mammographic density was higher in current (mean percent mammographic density 33%; 95% CI: 31–35%) than in former (29%; 95% CI 27% to 31) and never users (24%; 95% CI, 22–26%). Mammographic density increased with the duration of MHT within one year of therapy and reached a steady state thereafter. After discontinuation of the therapy, mammographic density decreased with time since last use and reached values similar to those of never users after 8 years. The OR of BC for current versus never MHT users, adjusted for age, year of birth, menopausal status at baseline and BMI, was 1.67 (95% CI, 1.04 to 2.68). The proportion of effect mediated by percent mammographic density was 34% on the log scale for any BC and became 48% when the correlation between BMI and percent mammographic density was accounted for. These results are limited to hormone receptor positive BCs.CONCLUSIONS: Our results suggest that under a causal model the effect of MHT on BC risk was partially mediated by MD that appeared to be modified by MHT for up to 8 years after MHT termination.
Differential kynurenine pathway metabolism in highly-metastatic aggressive breast cancer subtypes: beyond IDO1-induced immunosuppression
Authors: Heng Benjamin , Bilgin Ayse A. , Lovejoy David B , Tan Vanessa X , Milioli Heloisa Helena , Gluch Laurence , Moscato Pablo , Lim Chai K , Guillemin Gilles J 
Published: August 2020

Abstract
Background: Immunotherapy has recently been proposed as a promising treatment to stop breast cancer (BrCa) progression and metastasis. However, there has been limited success in the treatment of BrCa with immune checkpoint inhibitors. This implies that BrCa tumors have other mechanism(s) to escape immune surveillance. While the kynurenine pathway (KP) is known to be a key player mediating tumor immune evasion and while there are several studies on the roles of the KP in cancer, little is known about KP involvement in BrCa.Methods: To understand how KP is regulated in BrCa, we examined the KP profile in BrCa cell lines and clinical samples (n = 1,997) that represent major subtypes of BrCa (luminal, HER2, and triple-negative (TN)). We carried out qPCR, western blot/immunohistochemistry and ultra-high pressure liquid chromatography on these samples to quantify KP enzyme gene, protein and activity respectively.Results: We revealed that the KP is highly dysregulated in the HER2-enriched and TN BrCa subtype. Gene, protein expression and KP metabolomic profiling have shown that the downstream KP enzymes KMO and KYNU are highly upregulated in the HER2-enriched and TN BrCa subtypes, leading to increased production of the potent immunosuppressive metabolites anthranilic acid (AA) and 3-hydroxylanthranilic acid (3HAA).Conclusions: Our findings suggest that KMO and KYNU inhibitors may represent new promising therapeutic targets for BrCa. We also showed that KP metabolite profiling can be used as an accurate biomarker for BrCa subtyping, as we successfully discriminated TN BrCa from other BrCa subtypes.
Eribulin in combination with bevacizumab as second-line treatment for HER2–negative metastatic breast cancer progressing after first-line therapy with paclitaxel and bevacizumab: a multicenter, phase II, single arm trial (GIM11-BERGI)
Authors: DE ANGELIS CARMINE , Bruzzese Dario , Bernardo Antonio , Baldini Editta , Leo Luigi , Fabi Alessandra , Gamucci Teresa , De Placido Pietro , Poggio Francesca , Russo Stefania , Forestieri Valeria , Lauria Rossella , De Santo Irene , Michelotti Andrea , Mastro Lucia Del , De Laurentiis Michelino , Giuliano Mario , De Placido Sabino , Arpino Grazia 
Published: August 2020

Abstract
Background: Currently, there is no standard second-line chemotherapy-based treatment for patients with HER2-negative metastatic breast cancer (MBC). Continued VEGF inhibition with bevacizumab is an option in patients progressing to first-line bevacizumab and chemotherapy. Eribulin is a non-taxane microtubule dynamics inhibitor with a unique mechanism of action that has been shown to exert beneficial effects in the tumor microenvironment and on neoangiogenesis. We evaluated the efficacy and safety of eribulin plus bevacizumab in a novel second-line chemotherapy scheme in patients progressing after first-line paclitaxel and bevacizumab.Methods: This is a multicenter, single-arm, Simon's two-stage, phase II study. Patients with HER2-negative MBC progressing to paclitaxel and bevacizumab received eribulin (1.23 mg/m2 intravenously on days 1 and 8 of each 21-day cycle) plus bevacizumab (10 mg/kg every 2 weeks or 15 mg/kg every 3 weeks intravenously), as second-line chemotherapy. The primary endpoint was the overall response rate, considered as the sum of partial (PR) and complete response (CR) based on the best overall response (BORR).Results: Fifty-eight (95.1%) of the 61 patients enrolled in the study were evaluable for efficacy. The BORR was 24.6% (95% confidence intervals [CI], 14.5% to 37.3%). The CBR (i.e. the CR + PR + SD response that persisted for more than 24 weeks) was 32.8% (95% CI, 21.3% to 46.0%). The median progression-free survival was 6.2 months (95% CI, 4.0 to 7.8 months). Overall, adverse events (AEs) were clinically manageable and the most common were fatigue (9.9% of all AEs), paresthesia (6.5% of all AEs) and neutropenia (6.2% of all AEs). Moreover, 49.5% of AEs were related to eribulin, 7.7% to bevacizumab, and 11.8% to both drugs. Quality of life was well preserved in most patients.Conclusions: The results of this study suggest that continuing bevacizumab in combination with eribulin, beyond first line treatment with bevacizumab and paclitaxel is a reasonable therapeutic option for patients with HER2-negative MBC that exerts its effect without detrimentally affecting quality of life.Trial registration: clinicalTrial.gov: NCT02175446. Registered 26, June 2014. https://clinicaltrials.gov/ct2/show/NCT02175446
Activity Of Docetaxel, Carboplatin, And Doxorubicin In Patient-Derived Triple-Negative Breast Cancer Xenografts&nbsp;
Authors: Martin Miguel , Ramos-Medina Rocio , Bernat Rebeca , Saenz Jose Angel Garcia , Monte-Millan Maria Del , Alvarez Enrique , Cebollero Maria , Moreno Fernando , Haba Eva Gonzalez , Bueno Oscar , Romero Paula , Massarrah Tatiana , Echavarria Isabel , Jerez Yolanda , Herrero Blanca , Val Ricardo Gonzalez Del , Lobato Nerea , Rincon Patricia , Palomero Maria Isabel , Marquez-Rodas Ivan , Lizarraga Santiago , Asensio Fernando , Lopez-Tarruella Sara 
Published: August 2020

Abstract
Background: Triple-negative breast cancer (TNBC) is highly responsive to neoadjuvant polychemotherapy regimens including anthracyclines, taxanes, and, more recently, carboplatin. However, there is inadequate information on the individual contribution of each of these agents to the global activity of the combinations, and the use of combinations of up to four of these drugs is associated with relevant toxicity. Identifying single-drug activity in the clinical neoadjuvant setting is challenging. We developed patient-derived xenografts (PDXs) from several chemotherapy-naïve TNBC samples to assess the antitumor activity of single drugs and combinations of drugs. Methods: PDXs were established from chemotherapy-naïve TNBC samples. Nine TNBC PDX models (all of which corresponded to a basal-like phenotype according to the PAM50 classifier) were treated with carboplatin, docetaxel, and doxorubicin and the combination of docetaxel and carboplatin. Results: Only one of nine PDX models showed sensitivity to doxorubicin, while eight of nine PDX models showed sensitivity to docetaxel and carboplatin as single agents. All nine PDX models showed sensitivity to the combination of docetaxel and carboplatin. Conclusions: In the present study, docetaxel and carboplatin single agents were active drugs against basal-like TNBC, while doxorubicin monotherapy showed low activity. The combination of docetaxel and carboplatin was more effective than the drugs used as single agents.
The contribution of axillary lymph node volume to recurrence-free survival status in breast cancer patients with sub-stratification by molecular subtypes and pathological complete response
Authors: Kang James , Li Haifang , Cattell Renee , Talanki Varsha , Cohen Jules A , Bernstein Clifford S. , Duong Tim 
Published: August 2020

Abstract
Purpose This study sought to examine the contribution of axillary lymph node (LN) volume to recurrence-free survival (RFS) in breast cancer patients with sub-stratification by molecular subtypes, and full or nodal PCR.Methods The largest LN volumes per patient at pre-neoadjuvant chemotherapy on standard clinical breast 1.5-Tesla MRI, 3 molecular subtypes, full, breast, and nodal PCR, and 10-year RFS were tabulated (N = 110 patients from MRIs of I-SPY-1 TRIAL). A volume threshold of two standard deviations was used to categorize large versus small LNs for sub stratification. In addition, “normal” node volumes were determined from a different cohort of 218 axillary LNs.Results LN volume (4.07 ± 5.45 cm3) were significantly larger than normal axillary LN volumes (0.646 ± 0.657 cm3, P = 10− 16). Full and nodal pathologic complete response (PCR) was not dependent on pre-neoadjuvant chemotherapy nodal volume (P > .05). The HR+/HER2– group had smaller axillary LN volumes than the HER2 + and triple-negative groups (P < .05). Survival was not dependent on pre-treatment axillary LN volumes alone (P = .29). However, when substratified by PCR, the large LN group with full (P = .011) or nodal PCR (P = .0026) both showed better recurrence-free survival than the small LN group. There was significant difference in RFS when the small node group was separated by the 3 molecular subtypes (P = .036) but not the large node group (P = .97).Conclusions This study found an interaction of axillary lymph node volume, pathological complete responses, and molecular subtypes that inform recurrence-free survival status. Improved characterization of the axillary lymph nodes has the potential to improve the management of breast cancer patients.
Intraoperative radiation therapy for early stage breast cancer: experiences from Iran
Authors: Zangouri Vahid , Nasrollahi Hamid , Taheri Ali , Akrami Majid , Arasteh Peyman , Hamedi Seyed Hassan , Johari Masoumeh Ghoddusi , Karimaghaee Nazanin , Ranjbar Aliye , Tahmasebi Sedigheh , Mosalaei Ahmad , Talei Abdolrasoul 
Published: August 2020

Abstract
Background and objective Currently no definite guideline exists on the use of intraoperative radiation therapy (IORT) among patients with early stage BC. We report our experiences with IORT among breast cancer (BC) patients in our region.Methods All patient who received radical IORT from April 2014 on to March 2020 were included in the study. Patient selection criteria were as followed: age equal or older than 45 years old; all cases of invasive carcinomas, moreover in lobular carcinomas only after MRI and confirmation, and in cases with ductal carcinoma in-situ (DCIS) only those with low, intermediate grade, tumor size of equal or less than 2.5cm and a margin of 2-3mm; those between 45 and 50 years old with a tumor size of 0-2cm, those between 50 and 55 years old with a tumor size of 2-2.5cm, and those ≥55 years old with a tumor size of 2.5-3cm; those with invasive tumors a negative margin and in cases of DCIS a margin of 3mm; a negative nodal status (exception in patients with micrometastasis); and a positive estrogen receptor status. Results Overall, 252 patients entered the study. Mean (SD) age of patients was 56.43±7.79 years. In total, 32.9% of patients had a family history of BC. Mean tumor size was 1.56±0.55 cm. Median (IQR) follow-up of patients was 24 (13, 36) months. Overall, 6 patients (2.4%) experienced recurrence in follow-up visits, among which three (1.2%) were local recurrence, two (0.8%) were regional recurrence and one patients (0.4%) had metastasis.Median (IQR) time to recurrence was 23 (13, 36) among the six patient who had recurrence. Overall, 11 patients (4.3%) with DCIS in our study received IORT. All these patients had free margins in histopathology examination. None of these patients experience recurrence.Conclusion For the first time, we categorized patients according to age and tumor size and older patients with larger tumor sizes were considered appropriate candidates for IORT. Our series showed a successful experience with the use of IORT in a region where facilities for IORT are limited using our modified criteria for patient selection.
Influence of microbial fuel cell with porous anode on voltage generation, chemical oxygen demand, chloride content and total dissolved solids
Authors: Chaudhari Dhiraj , Dubey Harish , Kshirsagar Datta , Jadhav Vijay 
Published: August 2020

Abstract
Microbial fuel cells were developed using two different water sources: (1) unpolluted water (Kala Talao Lake) and (2) polluted water (Waldhuni River). The maximum output voltage provided by each source was compared, as was the cell voltage variation with anode porosity. The variation in power density of each cell with variation in anode porosity was also studied. The analysis of the MFCs' internal resistance (Rin) was also conducted and the variation with increased anode porosity was identified. The pH variation in both the MFCs is also reported. The cells' higher voltage output resulting in a lower pH was confirmed and variation of the pH gradient with increased porosity of anode was recorded. An analysis of the chemical oxygen demand (COD) values and water conductivity of the MFCs was also carried out. A significant drop in the COD values with increasing anode porosity occurred in both cells. The finding of increased porosity was also studied with decreased conductivity. In addition, variations in chloride content and total dissolved salts with porosity were performed.
Carica papaya in Cancer Prevention: An Overview
Authors: V.L. Maruthanila , Ramakrishnan Elancheran , Sankaran Mirunalini 
Published: August 2020

:
Carica papaya is an essential medicinal plant having anticancer activities through diverse mechanisms and is not
so far thoroughly investigated. In this review, we have summarized the systematic research outputs of different parts of the
papaya plant extracts and elaborated the role of its phytochemicals, anticancer activities, therapeutic targets and
mechanisms. Several phenolic compounds have been identified from this plant. Of these, Caffeic acid, Quinic acid and
Chlorogenic acid show significant properties and act as principal bioactive phytoconstituents among others. We have
explored the nutraceutical and functional aspects of Caffeic acid, Quinic acid and Chlorogenic acid along with the new
understanding of the mechanism and its action in diverse cancer models. Also, we have highlighted its bioavailability,
natural food additive properties and cost-effectiveness.
Association between Matrix Metalloproteinases, Their Tissue Inhibitor and White Matter Lesions in Mild Cognitive Impairment
Authors: Kimura Noriyuki , Aikawa Miki , Etou Kasumi , Aso Yasuhiro , Matsubara Etsuro 
Published: August 2020

Background:
White matter lesions are frequently found in mild cognitive impairments and
Alzheimer’s disease. Matrix metalloproteinases and the tissue inhibitor of metalloproteinases are implicated
in amyloid-β catabolism and blood brain barrier permeability. However, it remains unclear
whether they are associated with white matter lesions in Alzheimer’s disease.

Objective:
The aim of this study was to examine the association of matrix metalloproteinases and tissue
inhibitor of metalloproteinases with white matter degeneration in subjects with amyloid-positive mild
cognitive impairment.

Methods:
Thirty subjects with amnestic mild cognitive impairment (14 men and 16 women; mean age,
75.6 ± 5.8 years) underwent magnetic resonance imaging, 11C-Pittsburgh Compound B positron emission
tomography, and 18F-fluorodeoxyglucose positron emission tomography. Levels of plasma matrix
metalloproteinases and tissue inhibitor of metalloproteinases were measured using multiplex assays. All
subjects had an abnormal brain amyloid burden. Subjects were divided into two groups according to the
presence of white matter lesions using the Fazekas scale. Cognitive function testing results i.e., mean
11C-Pittsburgh Compound B and 18F-fluorodeoxyglucose uptake, concentrations of matrix metalloproteinases
and tissue inhibitor of metalloproteinases, and matrix metalloproteinases/tissue inhibitor of metalloproteinases
ratios were compared between the groups. Correlation analysis was conducted to investigate
the association between Fazekas scale score and clinical and neuroimaging variables as well as
concentrations of matrix metalloproteinases and tissue inhibitor of metalloproteinases.

Results:
Matrix metalloproteinases-2, -8, and -9 levels, matrix metalloproteinases-2/ tissue inhibitor of
metalloproteinases-2, matrix metalloproteinases-8/ tissue inhibitor of metalloproteinases-1, and matrix
metalloproteinases-9/tissue inhibitor of metalloproteinases-1 significantly increased and tissue inhibitor
of metalloproteinases-1 and-2 levels significantly decreased in the group with white matter lesions compared
with the group without white matter lesions. Matrix metalloproteinases-2, -8, and -9 levels correlated
positively and tissue inhibitor of metalloproteinases-1 and -2 levels correlated negatively with
Fazekas scale score.

Conclusion:
Plasma matrix metalloproteinases-2, -8, -9 and tissue inhibitor of metalloproteinases-1 and
-2 levels are associated with white matter lesions in the mild cognitive impairment stage of Alzheimer’s
disease.
Gut Alterations in Septic Patients: A Biochemical Literature Review
Authors: Longhitano Yaroslava , Zanza Christian , Thangathurai Duraiyah , Taurone Samanta , Kozel Daniela , Racca Fabrizio , Audo Andrea , Ravera Enrico , Migneco Alessio , Piccioni Andrea , Franceschi Francesco 
Published: August 2020

Background:
Sepsis is a life-threatening organ dysfunction with high mortality and morbidity
rate and with the disease progression many alterations are observed in different organs. The
gastrointestinal tract is often damaged during sepsis and septic shock and main symptoms are related
to increased permeability, bacterial translocation and malabsorption. These intestinal alterations
can be both cause and effect of sepsis.

Objective:
The aim of this review is to analyze different pathways that lead to intestinal alteration
in sepsis and to explore the most common methods for intestinal permeability measurement and, at
the same time to evaluate if their use permit to identify patients at high risk of sepsis and eventually
to estimate the prognosis.

Material and Methods:
The peer-reviewed articles analyzed were selected from PubMed databases
using the keywords “sepsis” “gut alteration”, “bowel permeability”, “gut alteration”, “bacterial
translocation”, “gut permeability tests”, “gut inflammation”. Among the 321 papers identified, 190
articles were selected, after title - abstract examination and removing the duplicates and studies on
pediatric population,only 105 articles relating to sepsis and gut alterations were analyzed.

Results:
Integrity of the intestinal barrier plays a key role in the preventing of bacterial translocation
and gut alteration related to sepsis. It is obvious that this dysfunction of the small intestine can
have serious consequences and the early identification of patients at risk - to develop malabsorption
or already malnourished - is very recommended to increase the survivor rate. Until now, in critical
patients, the dosage of citrullinemia is easily applied test in clinical setting, in fact, it is relatively
easy to administer and allows to accurately assess the functionality of enterocytes.

Conclusion:
The sepsis can have an important impact on the gastrointestinal function. In addition,
the alteration of the permeability can become a source of systemic infection. At the moment, biological
damage markers are not specific, but the dosage of LPS, citrulline, lactulose/mannitol test,
FABP and fecal calprotectin are becoming an excellent alternative with high specificity and sensitivity.
Application of Nanocellulose Derivatives as Drug Carriers; A Novel Approach in Drug Delivery
Authors: Khojastehfar Ali , Mahjoub Soleiman 
Published: August 2020

Background:
The production of nanocellulose for drug delivery systems has achieved increased attention in the past decade.
High capacity for swelling and absorption of the liquid phase, high flexibility in creating different derivatives, economical cost and ease
of access to the primary source, all of these properties have encouraged researchers to use nanocellulose and its derivatives as a highperformance drug carrier.

Objective:
We summarize the recent progresses of cellulose-based nanocarriers designing and practical approaches in
drug delivery.

Methods:
We conducted a literature review on the development of the nanocellulose and its derivatives as a highperformance drug carrier.

Results:
In this review, we have attempted to present the latest advances in cellulose modifications for the design of
pharmaceutical nanocarriers. at first, cellulose properties and structural classification of nanocellulose were introduced.
Then, focusing on medical applications, some efforts and laboratory trials in cellulose-based nano designing were also
discussed. The findings demonstrate the benefits of nanocellulose in drug delivery and its potential for modifying by
adding functional groups to enhance drug delivery efficiency. Due to the physical and chemical properties of cellulose and
its high flexibility to interact with other compounds, a broad perspective can be imagined in the diverse research and novel
forms of nanocarriers.

Conclusion:
The cellulose nanocarriers can be considered as an attractive platform for researchers to design new
structures of pharmaceutical carriers and increase the efficiency of these nanocarriers in drug delivery for the treatment of
diseases such as cancer.