bluuebunny/crossref_metadata_2025 huggingface dataset:
Dyslipidemia and Its Associated Factors in Women of the Bandare-Kong Cohort Study
Authors: Nikparvar Marzieh , Khaladeh Mohadeseh , Yousefi Hadi , Kheirandish Masoumeh
Published: August 2020

Background: Dyslipidemia, a major risk factor for cardiovascular diseases, has become a global issue. Due to geographic and demographic variations in the prevalence of dyslipidemia, this study aimed to evaluate dyslipidemia and its associated factors in women of the Bandare-Kong Cohort Study (BKNCD).Methods: This study was conducted on women from the population-based BKNCD, as part of the Prospective Epidemiological Research Studies in IrAN (PERSIAN). Sociodemographic data, medical history, and anthropometric indices were collected. Diastolic blood pressure, systolic blood pressure, fasting plasma glucose, serum triglyceride (TG), total cholesterol (TC), high-density lipoprotein (HDL), and low-density lipoprotein (LDL) were measured. Daily calorie intake and weekly metabolic equivalent of tasks were also recorded. Dyslipidemia was defined as any lipid abnormality based on the Adult Treatment Panel III criteria. Results: From the 2223 women in this study (mean age: 48.28±9.26 years), dyslipidemia was observed in 1884 (84.8%). High TC was the most common lipid abnormality (53.9%) followed by low HDL (50.8%). Dyslipidemia was most prevalent among women aged 65-70 years, the widowed, illiterate, unemployed, and overweight, with very low socioeconomic status, diabetes, and high waist circumference, hypertension, those using hookah and living in urban areas. Logistic regression revealed that only women with high WHR were at increased risk of dyslipidemia (OR=2.48, 95% CI:1.75-3.53, P<0.001). Having a high school diploma (OR=0.57, 95% CI:0.37-0.89, P=0.015) and living in rural areas (OR=0.68 95% CI:0.49-0.96, P=0.028) were protective.Conclusions: Dyslipidemia was highly prevalent in women of BKNCD. High WHR appears to be the only significant risk factor for dyslipidemia.
Morton Neuroma Surgery: Relation Clinical Results to Excised Sample Length
Authors: uzun metin , Tokat Fatma
Published: August 2020

Background:Morton’s neuroma (MN) is mechanical neuropathy of plantar interdigital nerve. It is one of the most common causes of forefoot pain. One of the most undesirable complications of MN surgery is recurrent neuroma. Excision level of MN is important to prevent recurrence. In this study, we aimed to find the relation resection lenght of MN to clinical results of MN surgery cases. Methods:76 samples sent with the diagnosis of Morton neuroma to the pathology department of our hospital between years 2010-2019. 66 patients whose clinical results were available were included in the study. Mean age was 41,5 (between 21 to 70). All of 66 patients were primary diagnosed 22 of them was left foot and the other 170 were right foot. 50 of them were female, and 16 were male. Recurrent neuromas, pathological sample more than one piece from one surgical site were excluded from the study. 72 of them were evaluated as a clinically and compare the sample lenght.Results:76 pathological specimens were prepared and examined by the same pathologist. Gross pathological appearance and histopathology findings were recorded. Mean sample length was 2,05 cm (between 0,7cm and 3,5 cm). 68 samples was smaller (89.5%) than 3 cm and only 8 sample (10.5%) was bigger than 3 cm. Average interdigital neuroma score improved from 20 to 62 points following the surgery (p<0.05).Conclusion:We recommend that, the common digital nerve should be cut from the proximal as much as possible to bury the proximal stump into the lumbrical muscles regardless of the sample size and using loupe magnification, careful and sharp dissection can be prevent injury to the PDNB.Level of Evidence: 2
Identification and integrated analysis of CircRNA and miRNA of Radiation-Induced lung injury in a mice model
Authors: Yang Xi , Li Yida , Zou Liqing , Chu Li , Ye Luxi , Ni Jianjiao , Chu Xiao , Guo Tiantian , Zhu Zhengfei
Published: August 2020

Radiation-induced lung injury (RILI) is a main threat to patients received thoracic radiotherapy, it is of great importance to understand the molecular mechanism of RILI. Circular RNAs (CircRNAs) have been found to act as the regulator of multiple biological processes and circRNA-miRNA-mRNA axis could play an important role in signaling pathway of many human diseases including radiation injury, here, we first investigate the circRNA and miRNA of radiation-induced lung injury in a mice model. The mice received 12 Gy thoracic irradiation and the irradiated lung tissues at 48 hours after irradiation were analyzed by RNA Sequencing (RNA-seq) technique compared with normal lung tissues. We identified 21 significantly up-regulated while significantly 33 down-regulated miRNAs. Among 27 differentially expressed circRNAs, 10 were down-regulated and 17 were up-regulated. We then performed circRNAs GO analysis of the target mRNAs of these significantly differently expressed circRNAs. These differentially expressed miRNAs took part in series of cellular processes such as positive regulation of alpha-beta T cell proliferation, interstitial matrix, collagen fibril organization, chemokine receptor activity, cellular defense response, and B cell receptor signaling pathway. Through this study, we found that immune-related molecular pathways play an important role in the early response after radiotherapy. In the future, research on the target mechanism and early intervention of circRNAs with associated miRNAs will benefit the treatment of RILI.
Deciphering the state of immune silence in fatal COVID-19 patients
Authors: Amit Ido , Bost Pierre , De Sanctis Francesco , Canè Stefania , Stefano Ugel , Donadello Katia , Castellucci Monica , David Eyal , Fiore Alessandra , Anselmi Cristina , Barouni Roza , Trovato Rosalinda , Caligola Simone , Lamolinara Alessia , Iezzi Manuela , Facciotti Federica , Mazzariol Anna , Gibellini Davide , De Nardo Pasquale , Tacconelli Evelina , Gottin Leonardo , Polati Enrico , Schwikowski Benno , Bronte Vincenzo
Published: August 2020

Since the beginning of the SARS-CoV-2 pandemic, COVID-19 has appeared as a unique disease with unconventional tissue and systemic immune features. While COVID-19 severe forms share clinical and laboratory aspects with various pathologies such as hemophagocytic lymphohistiocyto-sis, sepsis or cytokine release syndrome, their exact nature remains unknown. This is severely imped-ing the ability to treat patients facing severe stages of the disease. To this aim, we performed an in-depth, single-cell RNA-seq analysis of more than 150.000 immune cells isolated from matched blood samples and broncho-alveolar lavage fluids of COVID-19 patients and healthy controls, and integrated it with clinical, immunological and functional ex vivo data. We unveiled an immune sig-nature of disease severity that correlated with the accumulation of naïve lymphoid cells in the lung and an expansion and activation of myeloid cells in the periphery. Moreover, we demonstrated that myeloid-driven immune suppression is a hallmark of COVID-19 evolution and arginase 1 expression is significantly associated with monocyte immune regulatory features. Noteworthy, we found mon-ocyte and neutrophil immune suppression loss associated with fatal clinical outcome in severe pa-tients. Additionally, our analysis discovered that the strongest association of the patients clinical outcome and immune phenotype is the lung T cell response. We found that patients with a robust CXCR6+ effector memory T cell response have better outcomes. This result is line with the rs11385942 COVID-19 risk allel, which is in proximity to the CXCR6 gene and suggest effector memory T cell are a primary feature in COVID-19 patients. By systemically quantifying the viral landscape in the lung of severe patients, we indeed identified Herpes-Simplex-Virus 1 (HSV-1) as a potential opportunistic virus in COVID-19 patients. Lastly, we observed an unexpectedly high SARS-CoV-2 viral load in an immuno-compromised patient, allowing us to study the SARS-CoV-2 in-vivo life cycle. The development of myeloid dysfunctions and the impairment of lymphoid arm establish a condition of immune paralysis that supports secondary bacteria and virus infection and can progress to “immune silence” in patients facing death.
Congenital Muscular Dystrophy-Associated Inflammatory Chemokines Provide Axes for Effective Recruitment of Therapeutic Adult Stem Cell into Muscles
Authors: Alexeev Vitali , Olavarria Jacquelyn , Bonaldo Paolo , Merlini Luciano , Igoucheva Olga
Published: August 2020

Background: Congenital muscular dystrophies (CMD) are a clinically and genetically heterogeneous group of neuromuscular disorders characterized by muscle weakness. The two most prevalent forms of CMD, collagen VI-related myopathies (COL6RM) and laminin a2 deficient CMD type 1A (MDC1A), are both caused by deficiency or dysfunction of extracellular matrix proteins. Previously, we showed that an intramuscular transplantation of human adipose-derived stem cells (ADSC) into the muscle of the Col6a1-/- mice results in efficient stem cell engraftment, migration, long-term survival, and continuous production of the collagen VI protein, suggesting the feasibility of the systemic cellular therapy for COL6RM. In order for this therapeutic approach to work however, stem cells must be efficiently targeted to the entire body musculature. Thus, the main goal of this study is to test whether muscle homing of systemically transplanted ADSC can be enhanced by employing muscle-specific chemotactic signals originating from CMD-affected muscle tissue. Methods: Proteomic screens of chemotactic molecules were conducted in the skeletal muscles of COL6RM- and MDC1A-affected patients and CMD mouse models to define the inflammatory and immune activities, thus, providing potential markers of disease activity or treatment effect. Also using a pre-clinical animal model, recapitulating mild Ullrich congenital muscular dystrophy (UCMD), the therapeutic relevance of identified chemotactic pathways was investigated in vivo, providing a basis for future clinical investigations. Results: Comprehensive proteomic screens evaluating relevant human and mouse skeletal muscle biopsies offered chemotactic axes to enhance directional migration of systemically transplanted cells into CMD-affected muscles, including CCL5-CCR1/3/5, CCL2-CCR2, CXCL1/2-CXCR1,2 and CXCL7-CXCR2. Also, the specific populations of ADSC selected with an affinity for the chemokines being released by damaged muscle showed efficient migration to injured site and presented their therapeutic effect.Conclusions: Collectively, identified molecules provided insight into the mechanisms governing directional migration and intra-muscular trafficking of systemically infused stem cells, thus, permitting broad and effective application of the therapeutic adult stem cells for CMD treatment.
Uridine Diphosphate (UDP) Promotes Rheumatoid Arthritis Through P2Y6 Activation
Authors: Wang Hongxing , Wu Hui , Fang Kehua , Chang Xiaotian
Published: August 2020

Background: Uridine diphosphate (UDP) is an extracellular nucleotide signaling molecule implicated in diverse biological processes via specific activation of the metabotropic pyrimidine and purine nucleotide receptor pyrimidinergic receptor P2Y, G Protein-Coupled, 6 (P2Y6).Methods: This study used a quasi-targeted liquid chromatography-mass spectrometry (LC-MS) approach to investigate the unique expression of metabolites in rheumatoid arthritis (RA) synovial fluid (SF) (n=10) with samples from osteoarthritis (OA) as controls (n=10). RA fibroblast-like synoviocytes (FLSs) were collected from synovial tissues and cultured with UDP or MRS2578, P2Y6 antagonist, and FLSs from OA was used as controls. Rats with collagen-induced arthritis (CIA) were established and injected with UDP or MRS2578 or both. P2Y6 expression was examined using real-time PCR, Western blotting and Immunohistochemistry. Cell proliferation, apoptosis and migration of FLSs were measured using CCK-8 assay, real-time cell analysis, flow cytometry, the wound healing assay and transwell assay. The concentration of UDP in culture medium, synovial fluid and peripheral blood RA and CIA rats was measured using a Transcreener UDP Assay, IL-6 was measured using ELISA and flow assay, and other pro-inflammatory cytokines was measured using Th1/Th2 Subgroup Detection Kit. Results: LC-MS analysis showed that the UDP level is not only higher in RA SF than in OA SF but also positively correlated with anticyclic citrullinated peptide (anti-CCP) and rheumatoid factor (RF) levels in RA. The increased UDP concentration was verified in the plasma and SF samples of RA patients (n=36) and healthy volunteers (n=36), and the levels were significantly correlated with RF and anti-CCP level in the samples. The study also found that UDP stimulated the cell proliferation, migration and interleukin-6 (IL-6) secretion of RA FLSs and inhibited their apoptosis in the culture. The P2Y6 antagonist MRS2578 inhibited this effect of UDP in the culture. UDP injection accelerated the development of collagen-induced arthritis (CIA) in a rat model and stimulated IL-6 production, but simultaneous injection of MRS2578 suppressed these effects and alleviated CIA. P2Y6 expression was increased in RA and CIA synovial tissues and was unaltered by UDP treatment. UDP treatment and P2Y6 activity didn’t change levels of other proinflammatory cytokines in cultured FLSs and CIA rats.Conclusion: These results suggest that UDP is highly expressed in RA and stimulates RA pathogenesis by promoting P2Y6 activities to increase IL-6 production.
Spatiotemporal Prediction of COVID-19 Mortality and Risk Assessment
Authors: Torres-Signes Antoni , Frías M. Pilar , D.Ruiz-Medina María
Published: August 2020

This paper presents a multivariate functional data statistical approach, for spatiotemporal prediction of COVID-19 mortality counts. Specifically, spatial heterogeneous nonlinear parametric functional regression trend model fitting is first implemented. Classical and Bayesian infinite-dimensional log-Gaussian linear residual correlation analysis is then applied. The nonlinear regression predictor of the mortality risk is combined with the plug-in predictor of the multiplicative error term. An empirical model ranking, based on random K-fold validation, is established for COVID-19 mortality risk forecasting and assessment, involving Machine Learning (ML) models, and the adopted Classical and Bayesian semilinear estimation approach. This empirical analysis also determines the ML models favored by the spatial multivariate Functional Data Analysis (FDA) framework. The results could be extrapolated to other countries.
Estimation of drug-likeness properties of GC-MS separated bioactive compounds in rare medicinal Pleione maculata using molecular docking technique and SwissADME insilico tools
Authors: SYMPLI HAKANI D
Published: August 2020

The main aim of present paper is to determine bioactive compounds in Pleione maculata extracts using Gas chromatographic technique and to investigate their drug-likeness potential using molecular docking algorithm and ADME studies on the recent intractable disease for example; SARS-CoV-2. P. maculata sample was prepared for GC-MS analysis. The peak components are identified based on NIST Library. Molecular docking was performed using PatchDock and energy refinement was carried out using FireDock algorithm followed by drug-likeness analysis using Swiss ADME tool. Mass spectrum revealed various pharmacologically important compounds and novel compounds 8-oxatetracyclo{5.2.1.1(2,6). 1(4,10)}Dodecane, 7-tert-Butyl-1,9,9-Trimeth, Cholesterol Isocaproate, Docosane, 2,4-Dimethyl, 7.dehydrocholesterol isocaproate, Kryptogenin 2,4-dinitrophenyl hydrazine, N-decyl-Alpha,D-2-Deoxyglycoside, pyrimidine-2,4,6(1H,3H,5H)-Trione-1-octadecyl) which are reported for the first time. Molecular docking using PatchDock illustrates GC-MS compounds Nor-diazepam,3-{N-hydroxymethyl}aminocarbonyloxy a good docking and high binding affinity with Atomic contact energy -10.95 kcal/mol against SARS-CoV-2 Spike protein S2 subunit. ADME analysis predict Nor-diazepam,3-{N-hydroxymethyl}aminocarbonyloxy and andrographolide showed very high drug-likeness parameters with no metabolism disturbances. The random control anti-viral drug arabidiol revealed a lower binding energy and lower solubility compared to bioactive compounds of P. maculata. The study depicts the first and novel report on various pharmaceutical important GC-MS bioactive compounds and molecular docking study of Pleione maculata having potential against various intractable diseases.
Impact of Lockdown during COVID-19 on Annual Effective Dose Equivalent values of Natural Gamma Radiation
Authors: Jindal Manoj Kumar , Sar Santosh Kumar
Published: August 2020

The study aimed to find the impact of COVID-19 on values of Annual Effective Dose Equivalent of the natural Gamma dose rate from Balod, Durg and Bemetara districts of Chhattisgarh (India). COVID-19 is a severe problem for many countries and to control and prevent the spread of this problem implemented the lockdown approach in many countries, including India. In this lockdown situation, almost all people are staying at home for 24 hours. Due to the present status of COVID-19, the Indian government also fixed the 67 days lockdown and one day was already successfully done as Janta Curfew, which worked the same as a lockdown. The value of indoor gamma dose rates was reported higher in most places as compared to the outdoor gamma dose rate, but in this pandemic situation, occupancy factor values are not applicable as recommended by UNSCEAR for calculation of Annual Effective Dose Equivalent (AEDE). Therefore, the present study introduces the new equations, which can measure the extra AEDE value during the lockdown for adults, children and infants.
Artificial intelligence-based patient positioning for faster, more accurate and efficient CT imaging for COVID-19 patients
Authors: Gang Yadong , Chen Xiongfeng , Li Huan , Wang Hanlun , Li Jianying , Guo Ying , Zeng Junjie , Hu Qiang , Hu Jinxiang , Xu Haibo
Published: August 2020

Objective: To analyze and compare the imaging workflow, radiation dose and image quality for COVID-19 patients examined using either the conventional manual positioning method or an AI-based positioning method. Materials and Methods: 127 adult COVID-19 patients underwent chest CT scans on a CT scanner using the same scan protocol except with the manual positioning (MP group) for the initial scan and an AI-based positioning method (AP group) for the follow-up scan. Radiation dose, patient off-center distance, examination and positioning time of the two groups were recorded and compared. Image noise and signal-to-noise ratio (SNR) were assessed by three experienced radiologists and were compared between the two groups.Results: The AP group reduced the total positioning time and examination time by 28% and 8%, respectively compared with the MP group. Compared with the MP group, AP group had significantly less patient off-center distance (AP:1.56cm ± 0.83 vs. MP: 4.05cm ± 2.40, p<0.001) and higher proportion of positioning accuracy (AP: 99% vs. MP: 92%), resulted in 16% radiation dose reduction (AP: 6.1mSv ± 1.3 vs. MP: 7.3mSv ± 1.2, p<0.001) and 9% image noise reduction in erector spinae and lower noise and higher SNR for lesions in the pulmonary peripheral areas.Conclusion: The AI-based positioning and centering in CT imaging is a promising new technique for reducing radiation dose, optimizing imaging workflow and image quality in imaging the chest. This technique has important added clinical value in imaging COVID-19 patients to reduce the cross-infection risks.
Allergen Fragrance Molecules: A Potential Relief for COVID-19
Authors: Aydın Aslı Deniz , Altınel Faruk , Erdoğmuş Hüseyin , Son Cagdas Devrim
Published: August 2020

Background: The latest coronavirus SARS-CoV-2, discovered in China and rapidly spread Worldwide. COVID-19 affected millions of people and killed hundreds of thousands worldwide. There are many ongoing studies investigating drug(s) suitable for preventing and/or treating this pandemic; however, there are no specific drugs or vaccines available to treat or prevent SARS-CoV-2 as of today.Methods: 58 fragrance materials, which are classified as allergen fragrance molecules, were selected and used in this study. Docking simulations were carried out using four functional proteins; the Covid19 Main Protase (Mpro), Receptor binding domain (RBD) of spike protein, Nucleocapsid, and host Bromodomain protein (BRD2), as target macromolecules. Three different software, AutoDock, AutoDock Vina (Vina), and Molegro Virtual Docker (MVD), running a total of four different docking protocol with optimized energy functions were used. Results were compared with the five molecules reported in the literature as potential drugs against COVID-19. Virtual screening was carried out using Vina, molecules satisfying our cut-off (-6.5 kcal/mol) binding affinity was confirmed by MVD. Selected molecules were analyzed using the flexible docking protocol of Vina and AutoDock default settings. Results: Ten out of 58 allergen fragrance molecules were selected for further docking studies. Mpro and BRD2 are potential targets for the tested allergen fragrance molecules, while RBD and Nucleocapsid showed weak binding energies. According to AutoDock results, three molecules, Benzyl Cinnamate, Dihydroambrettolide, and Galaxolide, had good binding affinities to BRD2. While Dihydroambrettolide and Galaxolide showed the potential to bind to Mpro, Sclareol and Vertofix had the best calculated binding affinities to this target. When the flexible docking results analyzed, all the molecules tested had better calculated binding affinities as expected. Benzyl Benzoate and Benzyl Salicylate showed good binding affinities to BRD2. In the case of Mpro, Sclareol had the lowest binding affinity among all the tested allergen fragrance molecules. Conclusion: Allergen fragrance molecules are readily available, cost-efficient, and shown to be safe for human use. Results showed that several of these molecules had comparable binding affinities as the potential drug molecules reported in the literature to target proteins. Thus, these allergen molecules at correct doses could have significant health benefits.
Personal Protection with PBO-Pyrethroid Synergist Treated Nets After Two Years of Household Use Against Pyrethroid-Resistant Anopheles in Tanzania
Authors: Martin Jackline , Mosha Franklin W , Lukole Eliud , Rowland Mark , Todd Jim , Charlwood Jacques D , Mosha Jacklin F , Protopopoff Natacha
Published: August 2020

Background: The spread of pyrethroid resistance in malaria vectors threatens the effectiveness of standard long-lasting insecticidal nets (LLIN). Synergist nets combine pyrethroid (Py) and piperonyl-butoxide (PBO) to enhance potency against resistance mediated by mono-oxygenase mechanisms. Our project assessed personal protection of WHO first-in-class PBO-Py treated nets (Olyset Plus) versus standard LLIN (Olyset net) against pyrethroid resistant Anopheles gambiae and An. funestus in North West Tanzania after 20 months of household use.Methods: From household survey, 39 standard Olyset net and 39 Olyset Plus houses were selected, physical integrity and hole index (HI) of nets assessed, resting mosquitoes collected from inside nets and from room walls, indoor abundance estimated using CDC light traps and species identified using PCR. Residual bio-efficacy of PBO and standard LLINs was assessed using 30 min cylinder bioassays.Results: Of 2397 Anopheles collected, 8.9% (n=213) were resting inside standard Olyset nets while none were found inside Olyset Plus PBO-Py nets of any HI category. Resting density of blood fed mosquitoes was higher on walls of sleeping rooms with Olyset net compared to Olyset Plus (0.62 vs 0.10, density ratio: 0.03, 95% CI: 0.01-0.13, p<0.001). Mosquitoes were found inside Olyset nets of all WHO HI categories but more were collected inside the more damaged (HI≥ 643) nets than in less damaged (HI 0-64) nets (DR: 6.4, 95% CI: 1.1-36.0, p=0.037). In residual bioassay, mortality of An. gambiae s.l was higher with Olyset Plus than with Olyset net for new nets (76.8% vs 27.5%) and 20 months’ nets (56.8% vs 12.8%); similar trends were observed with An. funestus. Conclusion: The PBO-Py treated net provided improved protection after 20 months of household use, as demonstrated by the higher bioassay mortality and absence of pyrethroid resistant An. gambiae s.s. and An. funestus collected from inside Olyset Plus, irrespective of hole index category, as compared to Olyset nets.
Developmental Delay and Its Predictors Among Under-Five Uncomplicated Severe Acute Malnourished Children: a Cross-Sectional Study in Rural Areas of Pakistan
Authors: Saleem Javeria , Zakar Rubeena , Bukhari Gul Mehar Javaid , Fatima Aneela , Fischer Florian
Published: August 2020

Background: In developing countries, malnutrition in children and developmental delays are two major challenges for public health. To achieve the vision of the Sustainable Development Goals in the broader perspective of child health, an early identification of developmental delays and timely intervention is crucial. The aim of this study is to assess the prevalence of suspected developmental delay and their predictors in under-five uncomplicated severe acute malnourished children in rural areas of Pakistan.Methods: A multicentre cross-sectional study has been conducted among 185 uncomplicated severe acute malnourished children. We screened 6–59 months aged children for their nutritional status and clinical complications. Children fulfilling the inclusion criteria underwent the Denver Development Screening Tool II (DDSTII). The global developmental profile of children was calculated according to established protocols of DDSTII based on four important domains of development: personal and social behaviour, language, gross motor adaptive and fine motor adaptive skills. A pretested structured questionnaire on socio-demographic and nutritional factors was used for assessing predictors of developmental delay, which were analysed in a multivariate logistic regression model.Results: Out of 177 severe acute malnourished children, 69 (38.9%) had normal global development and 108 (61.1%) had delayed global development. Significant associations with global development delay were found for lower aged children (6-24 months vs. 25-59 month; AOR=4.53, 95% CI: 1.56–13.10, p<0.01), not exclusively breastfeed children (AOR=3.07, 95% CI: 1.24–7.56, p=0.01), and a history of contact with tuberculosis smear positive adult (AOR=2.67, 95% CI: 1.30–5.49, p<0.01). Conclusion: With about two thirds of study participants showing delayed or unstable global development, there is a high prevalence of suspected developmental delay among under-five uncomplicated severe acute malnourished children in rural areas Pakistan. Particularly children in their first two years of life with insufficient breastfeeding are at high risk. This emphasizes the need for providing adequate infrastructure and information to parents in remote areas.
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

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

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

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 
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

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

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

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.
Stakeholder approach to selecting enterprise-bank interaction strategies
Authors: M. Hutsaliuk Oleksii , V. Yaroshevska Oksana , M. Shmatko Nataliia , V. Kulko-Labyntseva Inna , S. Navolokina Alla
Published: August 2020

Stakeholder theory dominates in revealing the features of the stakeholders’ influence on various entities; however, only few studies rely on it in the field of enterprises that select banks as financial partners. Considering the enterprise-bank relationship from the stakeholder theory perspective, this paper represents an approach to selecting strategies for interaction with this stakeholder type.The proposed approach includes the following steps: determining the interaction objectives for enterprises and banks; specifying and comparing potential partners; ranking banks to justify the chosen partner/partners for interaction; and selecting interaction strategies and forming the content of the behavior patterns inherent in enterprises (offensive or negotiation strategies). The criteria for choosing a strategy include the objectives of the interaction between enterprises (providing comprehensive services or satisfying individual financial needs) and their financial status that determines the interest of banks in partnership.The application of the proposed methodology for calculating rating indicators and the respective bank ranking showed that 18% of the banks included in the studied list of reliable Ukrainian banks have a high level of innovation activity and an acceptable level of banking service costs for business customers (that is, they implement a customer-oriented policy). Therefore, to receive comprehensive banking services combined with high or medium levels of banks’ interest in interaction, the paper recommends enterprises to choose a large-scale offensive strategy or a large-scale negotiation strategy, respectively.The stakeholder theory, as well as consideration of the criteria defined in the paper, will allow enterprises to choose interaction strategies that meet their needs for financial services and harmonize the interests of partners.
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

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.