bluuebunny/crossref_metadata_2025_split huggingface dataset:
Vitamin D Regulates CXCL12/CXCR4 and Epithelial-to-Mesenchymal Transition in a Model of Breast Cancer Metastasis to Lung
Authors: Li Jiarong , Luco Aimée-Lee , Camirand Anne , St-Arnaud René , Kremer Richard 
Published: March 2021

Abstract
Vitamin D deficiency is associated with poor cancer outcome in humans, and administration of vitamin D or its analogs decreases tumor progression and metastasis in animal models. Using the mouse mammary tumor virus-polyoma middle T antigen (MMTV-PyMT) model of mammary cancer, we previously demonstrated a significant acceleration of carcinogenesis in animals on a low vitamin D diet and a reduction in spontaneous lung metastases when mice received vitamin D through perfusion. We investigate here the action mechanism for vitamin D in lung metastasis in the same non-immunodeficient model and demonstrate that it involves the control of epithelial to mesenchymal transition as well as interactions between chemokine C-X-C motif chemokine 12 (CXCL12) and its receptor C-X-C chemokine receptor type 4 (CXCR4). In vitro, 10−9M vitamin D treatment modifies the phenotype of MMTV-PyMT primary mammary tumor cells and significantly decreases their invasiveness and mammosphere formation capacity by 40% and 50%, respectively. Vitamin D treatment also inhibits phospho-signal transducer and activator of transcription 3 (p-STAT3), zinc finger E-box-binding homeobox 1 (Zeb1), and vimentin by 52%, 75%, and 77%, respectively, and increases E-cadherin by 87%. In vivo, dietary vitamin D deficiency maintains high levels of Zeb1 and p-STAT3 in cells from primary mammary tumors and increases CXCL12 expression in lung stroma by 64%. In lung metastases, vitamin D deficiency increases CXCL12/CXCR4 co-localization by a factor of 2.5. These findings indicate an involvement of vitamin D in mammary cancer ”seed” (primary tumor cell) and ”soil” (metastatic site) and link vitamin D deficiency to epithelial-to-mesenchymal transition (EMT), CXCL12/CXCR4 signaling, and accelerated metastasis, suggesting vitamin D repleteness in breast cancer patients could enhance the efficacy of co-administered therapies in preventing spread to distant organs.
Prolonged Low-Dose Dioxin Exposure Impairs Metabolic Adaptability to High-Fat Diet Feeding in Female but Not Male Mice
Authors: Matteo Geronimo , Hoyeck Myriam P , Blair Hannah L , Zebarth Julia , Rick Kayleigh R C , Williams Andrew , Gagné Rémi , Buick Julie K , Yauk Carole L , Bruin Jennifer E 
Published: March 2021

Abstract

Context
Human studies consistently show an association between exposure to persistent organic pollutants, including 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD, aka “dioxin”), and increased diabetes risk. We previously showed that a single high-dose TCDD exposure (20 µg/kg) decreased plasma insulin levels in male and female mice in vivo, but effects on glucose homeostasis were sex-dependent.

Objective
The current study assessed whether prolonged exposure to a physiologically relevant low-dose of TCDD impacts glucose homeostasis and/or the islet phenotype in a sex-dependent manner in chow-fed or high-fat diet (HFD)-fed mice.

Methods
Male and female mice were exposed to 20 ng/kg/d TCDD 2×/week for 12 weeks and simultaneously fed standard chow or a 45% HFD. Glucose homeostasis was assessed by glucose and insulin tolerance tests, and glucose-induced plasma insulin levels were measured in vivo. Histological analysis was performed on pancreas from male and female mice, and islets were isolated from females for TempO-Seq transcriptomic analysis.

Results
Low-dose TCDD exposure did not lead to adverse metabolic consequences in chow-fed male or female mice, or in HFD-fed males. However, TCDD accelerated the onset of HFD-induced hyperglycemia and impaired glucose-induced plasma insulin levels in females. TCDD caused a modest increase in islet area in males but reduced the percent beta cell area within islets in females. TempO-Seq analysis suggested abnormal changes to endocrine and metabolic pathways in female TCDDHFD islets.

Conclusion
Our data suggest that prolonged low-dose TCDD exposure has minimal effects on glucose homeostasis and islet morphology in chow-fed male and female mice but promotes maladaptive metabolic responses in HFD-fed females.
Humanin Alleviates Insulin Resistance in Polycystic Ovary Syndrome: A Human and Rat Model–Based Study
Authors: Wang Yingying , Zeng Zhengyan , Zhao Shuhua , Tang Li , Yan Jin , Li Nianyu , Zou Liping , Fan Xiaorong , Xu Chengcheng , Huang Jin , Xia Wei , Zhu Changhong , Rao Meng 
Published: March 2021

Abstract
Polycystic ovary syndrome (PCOS), the most common endocrine disorder in women of reproductive age, is characterized by hyperandrogenism and insulin resistance (IR); however, the pathogenesis of local ovarian IR in PCOS remains largely unclear. Humanin, a mitochondria-derived peptide, has been reported to be associated with IR. Our previous study confirmed that humanin is expressed in multiple cell types in the ovary and is present in follicular fluid. However, it remains unknown whether humanin participates in the pathogenesis of local ovarian IR or whether humanin supplementation can improve IR in PCOS patients. In this study, we compared humanin concentrations in follicular fluid from PCOS patients with and without IR. We further investigated the effect of humanin analogue (HNG) supplementation on IR in a rat model of dehydroepiandrosterone-induced PCOS. Humanin concentrations in the follicular fluid were found to be significantly lower in PCOS patients with IR than in those without IR. HNG supplementation attenuated both the increases in the levels of fasting plasma glucose and fasting insulin in rats with PCOS and the decreases in phosphorylation of IRS1, PI3K, AKT, and GLUT4 proteins in the granulosa cells of these rats. Combined supplementation with HNG and insulin significantly improved glucose consumption in normal and humanin-siRNA-transfected COV434 cells. In conclusion, downregulated humanin in the ovaries may be involved in the pathogenesis of IR in PCOS, and exogenous supplementation with HNG improved local ovarian IR through modulation of the IRS1/PI3K/Akt signaling pathway in a rat model. This finding supports the potential future use of HNG as a therapeutic drug for PCOS.
Considering Sex as a Biological Variable in Basic and Clinical Studies: An Endocrine Society Scientific Statement
Authors: Bhargava Aditi , Arnold Arthur P , Bangasser Debra A , Denton Kate M , Gupta Arpana , Hilliard Krause Lucinda M , Mayer Emeran A , McCarthy Margaret , Miller Walter L , Raznahan Armin , Verma Ragini 
Published: March 2021

AbstractIn May 2014, the National Institutes of Health (NIH) stated its intent to “require applicants to consider sex as a biological variable (SABV) in the design and analysis of NIH-funded research involving animals and cells.” Since then, proposed research plans that include animals routinely state that both sexes/genders will be used; however, in many instances, researchers and reviewers are at a loss about the issue of sex differences. Moreover, the terms sex and gender are used interchangeably by many researchers, further complicating the issue. In addition, the sex or gender of the researcher might influence study outcomes, especially those concerning behavioral studies, in both animals and humans. The act of observation may change the outcome (the “observer effect”) and any experimental manipulation, no matter how well-controlled, is subject to it. This is nowhere more applicable than in physiology and behavior. The sex of established cultured cell lines is another issue, in addition to aneuploidy; chromosomal numbers can change as cells are passaged. Additionally, culture medium contains steroids, growth hormone, and insulin that might influence expression of various genes. These issues often are not taken into account, determined, or even considered. Issues pertaining to the “sex” of cultured cells are beyond the scope of this Statement. However, we will discuss the factors that influence sex and gender in both basic research (that using animal models) and clinical research (that involving human subjects), as well as in some areas of science where sex differences are routinely studied. Sex differences in baseline physiology and associated mechanisms form the foundation for understanding sex differences in diseases pathology, treatments, and outcomes. The purpose of this Statement is to highlight lessons learned, caveats, and what to consider when evaluating data pertaining to sex differences, using 3 areas of research as examples; it is not intended to serve as a guideline for research design.
ER Stress in Cardiometabolic Diseases: From Molecular Mechanisms to Therapeutics
Authors: Ajoolabady Amir , Wang Shuyi , Kroemer Guido , Klionsky Daniel J , Uversky Vladimir N , Sowers James R , Aslkhodapasandhokmabad Hamid , Bi Yaguang , Ge Junbo , Ren Jun 
Published: March 2021

Abstract
The endoplasmic reticulum (ER) hosts linear polypeptides and fosters natural folding of proteins through ER-residing chaperones and enzymes. Failure of the ER to align and compose proper protein architecture leads to accumulation of misfolded/unfolded proteins in the ER lumen, which disturbs ER homeostasis to provoke ER stress. Presence of ER stress initiates the cytoprotective unfolded protein response (UPR) to restore ER homeostasis or instigates a rather maladaptive UPR to promote cell death. Although a wide array of cellular processes such as persistent autophagy, dysregulated mitophagy, and secretion of proinflammatory cytokines may contribute to the onset and progression of cardiometabolic diseases, it is well perceived that ER stress also evokes the onset and development of cardiometabolic diseases, particularly cardiovascular diseases (CVDs), diabetes mellitus, obesity, and chronic kidney disease (CKD). Meanwhile, these pathological conditions further aggravate ER stress, creating a rather vicious cycle. Here in this review, we aimed at summarizing and updating the available information on ER stress in CVDs, diabetes mellitus, obesity, and CKD, hoping to offer novel insights for the management of these cardiometabolic comorbidities through regulation of ER stress.
Use of Statins Among Patients Taking Levothyroxine: an Observational Drug Utilization Study Across Sites
Authors: Idrees Thaer , Prieto Wesley H , Casula Sabina , Ajith Aswathy , Ettleson Matthew , Narchi Flavia A Andreotti , Russo Pedro S T , Fernandes Fernando , Johnson Julie , Mayampurath Anoop , Maciel Rui M B , Bianco Antonio C 
Published: March 2021

Abstract

Context
Treatment with levothyroxine (LT4) that normalize serum thyrotropin (TSH) is expected to restore lipid metabolism.

Objective
To assess statin utilization in LT4-treated patients through an observational drug utilization study.

Methods
Three sites were involved: (1) 10 723 outpatients placed on LT4 during 2006-2019 identified from the Clinical Research Data Warehouse of the University of Chicago; (2) ~1.4 million LT4 prescriptions prepared by primary care physicians during January-December 2018, identified from the IQVIA™ database of medical prescriptions in Brazil; (30 ~5.4 million patient interviews during 2009-2019, including ~0.32 million patients on LT4, identified from the Fleury Group database in Brazil.

Results
On site 1, initiation of therapy with LT4 increased the frequency of statin utilization (19.1% vs 24.6%), which occurred ~1.5 years later (median 76 weeks) and, among those patients that were on statins, increased intensity of treatment by 33%, despite normalization of serum TSH levels; on site 2, after matching for sex and age, the frequency of statins prescription was higher for those patients using LT4: females, 2.1 vs 3.4% (odds ratio [OR] 1.656 [1.639-1.673]); males, 3.1 vs 4.4% (OR 1.435 [1.409-1.462]); and, on site 3, after matching for sex and age, the frequency of statin utilization was higher in those patients using LT4: females, 10 vs 18% (OR 2.02 [2.00-2.04]); males, 15 vs 25% (OR 1.92 [1.88-1.96]); all P values were &lt;.0001.

Conclusion
Prescription and utilization of statins were higher in patients taking LT4. The reasons for this association should be addressed in future studies.
Visual cues enhance obstacle avoidance in echolocating bats
Authors: Jones Te K. , Moss Cynthia F. 
Published: March 2021

ABSTRACTStudies have shown that bats are capable of using visual information for a variety of purposes, including navigation and foraging, but the relative contributions of visual and auditory modalities in obstacle avoidance has yet to be fully investigated, particularly in laryngeal echolocating bats. A first step requires the characterization of behavioral responses to different combinations of sensory cues. Here, we quantified the behavioral responses of the insectivorous big brown bat, Eptesicus fuscus, in an obstacle avoidance task offering different combinations of auditory and visual cues. To do so, we utilized a new method that eliminates the confounds typically associated with testing bat vision and precludes auditory cues. We found that the presence of visual and auditory cues together enhances bats' avoidance response to obstacles compared with cues requiring either vision or audition alone. Analyses of flight and echolocation behaviors, such as speed and call rate, did not vary significantly under different obstacle conditions, and thus are not informative indicators of a bat's response to obstacle stimulus type. These findings advance the understanding of the relative importance of visual and auditory sensory modalities in guiding obstacle avoidance behaviors.
Multi-Mode Switchable Luminescence of Tetranuclear Cubic Copper(I) Iodide Complexes with Tertiary Arsine Ligands
Authors: Kobayashi Ryosuke , Inaba Ryoto , Imoto Hiroaki , Naka Kensuke 
Published: March 2021

Abstract
Tetranuclear cubic copper(I) iodide (CuI) complexes were synthesized by utilizing tertiary arsine ligands such as triphenylarsine, tri(p-tolyl)arsine, 9-phenyl-9-arsafluorene, and 1-phenylarsolane; except for triphenylarsine, these ligands were prepared by the practical methods that we previously developed. The obtained complexes exhibited intense emission in the crystalline states even at room temperature. Their emission colors were drastically changed by mechanical stimulus, temperature, and excitation wavelength. These complexes are the first examples of cubic Cu4I4 complexes with arsenic ligands exhibiting stimuli-responsive and excitation wavelength-dependent luminescence.
Elucidation of Nitrogen Adsorption Behavior of AlMepO-α by In-Situ Powder X-ray Diffraction Study
Authors: Maeda Kazuyuki , Minta Hiroaki , Kondo Atsushi , Kawaguchi Shogo 
Published: March 2021

Abstract
In-situ powder X-ray diffraction study of AlMepO-α under varied nitrogen equilibrium pressures identifies two phases np and lp with the same space group and slightly different lattice constants and reveals their structures with different nitrogen contents. A crystallographically estimated adsorption isotherm fairly well simulates the measured two-step isotherm.
Zuotai (β-HgS)-containing 70 Wei Zhen-Zhu-Wan differs from mercury chloride and methylmercury on hepatic cytochrome P450 in mice
Authors: Nie Yu , Xu Shang-Fu , Lu Yan-Liu , Zhao Xiu-Rong , Li Cen , Wei Li-Xin , Liu Jie 
Published: March 2021

Background: Zuotai (mainly β-HgS)-containing 70 Wei-Zhen-Zhu-Wan (70W, Rannasangpei) is a famous Tibetan medicine for treating cardiovascular and gastrointestinal diseases. We have shown that 70W protected against CCl4 hepatotoxicity. CCl4 is metabolized via cytochrome P450 (CYP) to produce reactive metabolites. Whether 70W has any effect on CYPs is unknown and such effects should be compared with mercury compounds for safety evaluation. Methods: Mice were given clinical doses of 70W (0.15-1.5 g/kg, po), Zuotai (30 mg/kg, po), and compared to HgCl2 (33.6 mg/kg, po) and MeHg (3.1 mg/kg, po) for seven days. Liver RNA and protein were isolated for qPCR and Western-blot analysis. Results: 70W and Zuotai had no effects on hepatic mRNA expression of Cyp1a2, Cyp2b10, Cyp3a11, Cyp4a10 and Cyp7a1, and corresponding nuclear receptors [aryl hydrocarbon receptor (AhR), constitutive androstane receptor (CAR), pregnane X receptor (PXR), peroxisome proliferator-activated receptor-α (PPARα); farnesoid X receptor (FXR)]. In comparison, HgCl2 and MeHg increased mRNA expression of Cyp1a2, Cyp2b10, Cyp4a10 and Cyp7a1 except for Cyp3a11, and corresponding nuclear receptors except for PXR. Western-blot confirmed mRNA results, showing increases in CYP1A2, CYP2B1, CYP2E1, CYP4A and CYP7A1 by HgCl2 and MeHg only, and all treatments had no effects on CYP3A. Conclusions: Zuotai and Zuotai-containing 70W at clinical doses had minimal influence on hepatic CYPs and corresponding nuclear receptors, while HgCl2 and MeHg produced significant effects. Thus, the use of total Hg content to evaluate the safety of HgS-containing 70W is inappropriate.
Ormianie w Zamościu w pierwszych trzech dekadach istnienia miasta (1580-1610)
Authors: Majewski Marcin Łukasz 
Published: March 2021

Armenians in Zamość in the first three decades of the city’s existence
Armenian settlement in Zamość was legally based on the privilege issuedon April 30, 1585 in Belz by the Grand Chancellor of the Crown, Jan Zamoyski,acting as a private owner of the city. Most likely, however, the first Armeniansbegan to arrive in the city even before the official announcement of the privilege.The author presents the process of their settlement in Zamość in the years 1580-1610, discusses the activity of the first Armenian settlers in the city’s life, especiallyin trade, crafts and real estate, as well as the emergence of the representation of thisethnic group in the city authorities and their own community.
Uses and Properties of some Adverbs in Contemporary French and Spanish: honnêtement and sérieusement vs. honestamente, seriamente and en serio
Authors: Álvarez-Prendes Emma 
Published: March 2021

In this paper we propose to examine and contrast the functioning of five adverbs in contemporary French (sérieusement and honnêtement) and Spanish (honestamente, seriamente and en serio). Our aim is threefold:– To verify the different uses of honnêtement and sérieusement in French, and to compare them with the uses of honestamente, seriamente and en serio in Spanish.– To justify the existence of these uses in terms of their different properties.– To examine the origin and historical evolution of these uses and to explain their common origin as a result of a process of subjectification.
A diachronic analysis of visiblement/visiblemente: contemporary false-friends
Authors: Gómez-Jordana Sonia 
Published: March 2021

The aim of this paper is to establish how the French adverb visiblement has evolved, and to find the most accurate translations of this adverb in Spanish. Dictionaries tend to give literal translations, whereby visiblement is translated as visiblemente. A diachronic analysis of this adverb will enable us to see whether they are indeed false-friends. In Old French and in Pre-classical French, it was used as a clause element adverb, before being used as a disjunct adverb from the 17th century onwards. Eventually, it goes on to appear by itself, or, accompanying an affirmative, like oui, in the 20th century. We will demonstrate that the adverb undergoes a process of pragmaticalisation as described by Dostie (2004), with the adverb becoming more subjective, going from a literal sense, to a disjunct or pragmatic adverb. Nevertheless, in Spanish, since Old Spanish until nowadays, there are almost no examples other than its use as a clause element adverb. That’s the reason why we cannot propose a literal translation of the adverb.
Perubahan sebaran dan kerapatan hutan mangrove di Pesisir Pantai Bama, Taman Nasional Baluran menggunakan citra satelit SPOT 4 dan SPOT 6
Authors: Fudloly Andhika Rahmatullah Laksmana , Fuad Mochammad Arif Zainul , Purwanto Anang Dwi 
Published: March 2021

The condition of mangrove forests in the Baluran National Park area is always changing. Mapping changes of mangrove area and density is needed to find out areas that need attention for mangrove conservation. The study aimed to determine the distribution and the density of mangrove forests in coastal waters of Bama, Baluran National Park. The image data used were SPOT 4 acquisition in 2007 and SPOT 6 acquisition in 2017 as well as field data that have been collected on 23-25 January 2019. The method of separating mangrove and non-mangrove objects used supervised classification, whereas for estimating the density of mangrove using the Normalized Difference Vegetation Index (NDVI) algorithm. The results showed the distribution of mangrove forests in coastal waters of Bama, Baluran National Park from 2007-2017 decreased in area by 8.9 ha. In contrast, the condition of mangrove density increased significantly, where the changes in mangrove density were dominated in the high-density class. The results of the accuracy tests using the method confusion matrix obtained an overall accuracy of 88%, while the accuracy-test with the kappa method obtained an accuracy of 87.76%. The resulting accuracy value indicates a high level of accuracy (more than 85%) and according to the specified requirements.Keywords: Mangrove, NDVI, SPOT 4, SPOT 6, Baluran National Park ABSTRAKKondisi luasan hutan mangrove di kawasan Taman Nasional Baluran terus mengalami perubahan. Pemetaan perubahan luasan dan kerapatan mangrove sangat diperlukan untuk mengetahui area yang membutuhkan perhatian untuk pelestarian mangrove. Penelitian ini bertujuan untuk mengetahui sebaran dan kerapatan hutan mangrove di pesisir pantai Bama, Taman Nasional Baluran. Data yang digunakan dalam penelitian adalah citra SPOT 4 akuisisi tahun 2007 dan citra SPOT 6 akuisisi tahun 2017 dan data hasil survei lapangan yang telah dilakukan pada tanggal 23 - 25 Januari 2019. Metode pemisahan obyek mangrove dan non mangrove menggunakan klasifikasi terbimbing (supervised), sedangkan untuk pendugaan tingkat kerapatan mangrove menggunakan algoritma Normalized Difference Vegetation Index (NDVI). Hasil penelitian menunjukkan sebaran hutan mangrove di pesisir pantai Bama, Taman Nasional Baluran dari tahun 2007-2017 mengalami penurunan luasan sebesar 8,9 ha, sedangkan kondisi tingkat kerapatan mangrove mengalami peningkatan yang cukup signifikan dimana perubahan kerapatan mangrove didominasi pada kelas kerapatan rapat. Hasil uji akurasi menggunakan metode matriks kesalahan (confusion matrix) memperoleh overall accuracy sebesar 88%, sedangkan uji akurasi dengan metode kappa diperoleh tingkat akurasi sebesar 87,76%. Nilai akurasi yang dihasilkan menunjukkan tingkat ketelitian yang cukup tinggi (lebih dari 85%) dan telah memenuhi syarat yang ditetapkan.Kata kunci: Mangrove, NDVI, SPOT 4, SPOT 6, Taman Nasional Baluran