bluuebunny/crossref_metadata_2025 huggingface dataset:
Acute supplementation with beetroot juice improves endothelial function in HIV-infected individuals
Authors: Nogueira Soares Rogerio , Machado-Santos Ana Paula , Barros-Santos Elisa , Vieira De Oliveira Gustavo , Murias Juan Manuel , Alvares Thiago Silveira
Published: August 2020

Human immunodeficiency virus (HIV) is associated with lower nitric oxide (NO) bioavailability and vascular dysfunction. Nitrate-rich beetroot juice (BJ) has been shown to acutely increase NO availability and vascular function in healthy and individuals at high risk for cardiovascular disease. Thus, we tested the effects of BJ ingestion on flow-mediated dilation (FMD) and pulse wave velocity (PWV) measurements in healthy and HIV-infected patients. Thirteen HIV-infected individuals (age, 36 ± 10 years) and 18 healthy (age, 27 ± 8 years) participated in the study. Individuals were submitted to vascular tests such as FMD and pulse PWV at pre (T0) and at 120 min (T120) after BJ and placebo (PLA) ingestion. The %FMD at T0 of the control group was significantly higher than the %FMD at T0 of the HIV individuals in both interventions. BJ improved the %FMD at T120 when compared with T0 in the HIV and control groups. There was no change in %FMD after PLA ingestion in the control and HIV groups. There were no differences between groups (control vs HIV), time points (T0 vs T120), and interventions (BJ vs PLA) for PWV. Our findings showed that nitrate-rich BJ ingestion acutely improved vascular function in healthy and HIV-infected patients. Clinical Trials Registry no. NCT03485248.

Novelty: HIV is associated with lower NO bioavailability and vascular dysfunction. Acute supplementation with nitrate-rich BJ has been shown to acutely increases NO bioavailability. We showed for the first time that BJ acutely improves endothelial function in HIV-infected patients.
Are Type Ia supernova powerful tool to detect anisotropic expansion of the Universe?
Authors: Salehi A. , Farajollahi H. , Motahari M. , Pashamokhtari P. , Yarahmadi M. , Fathi S.
Published: August 2020

In this paper, we present a detailed analysis of the dark energy dipole using Union2, Pantheon and GRB dataset in Chameleon and Teleparallel dark energy models, in comparison with$$\Lambda $$ΛCDM. Both models are extensively studied in recent years and our result shows that with Union2 and Pantheon data, the preferred direction of the anisotropy in both models are very close to each other as well as with those obtained in some studies for$$\Lambda $$ΛCDM. However, when the models fitted with a combination of Union 2 and GRB, the statistical analysis slightly favors the Chameleon cosmology over Teleparallel gravity, with the maximum anisotropic direction of$$(l = 330^{+30}_{-28}$$(l=330-28+30,$$b = -15^{+23}_{-25})$$b=-15-25+23)in galactic coordinate system, comparable with$$\alpha $$α-dipole result in Keck-VLT data and LCDM.
Phenomenology of the Pauli exclusion principle violations due to the non-perturbative generalized uncertainty principle
Authors: Addazi Andrea , Belli Pierluigi , Bernabei Rita , Marcianò Antonino , Shababi Homa
Published: August 2020

New phenomenological implications of the Generalized Uncertainty Principle (GUP), a modification of the Heisenberg Uncertainty Principle (HUP) are explored in light of constraints arising from underground experiments. An intimate link intertwines the symplectic structure of a theory, which is at the very base of the formulation of the HUP and thus a pillar of quantum mechanics, with the symmetries of space-time and the spin-statistics. Within this wide framework, a large class of non-perturbative GUPs inevitably lead to energy-dependent violations of the total angular momentum conservation rules, and imply hence tiny Pauli Exclusion Principle (PEP) violating transitions. Exotic PEP violating nuclear transitions can be tested, for example, through extremely high precision data provided by the DAMA/LIBRA experiment. We show that several GUP violations are already ruled out up to the quantum gravity Planck scale.
Few Remarks on Quasi Quantum Quadratic Operators on 𝕄2(ℂ)
Authors: Mukhamedov Farrukh , Syam Sondos M. , Almazrouei Shamma A.Y.
Published: August 2020

The present paper deals with a connection between quantum quadratic operators (QQOs) and quasi QQOs on 𝕄2(ℂ). We show that QQOs and quasi QQOs on 𝕄2(ℂ) coincide in the class of Volterra type of operators. To establish this result, we first describe these two kind of operators on the commutative part of 𝕄2(ℂ). Furthermore, in the last section, we introduce a quantum analogue of Volterra operators and provide concrete examples of such kind of operators. It is established that the considered examples also satisfy quasiness condition as well. The obtained results will allow to produce (with explicit conditions) a class of unital, but not trace-preserving positive maps of 𝕄2(ℂ).
Quantum Error Correction in the Presence of Initial System-Environment Correlations
Authors: Türkmen A. , Verçin A.
Published: August 2020

Quantum error correction is studied in a framework consisting of an open quantum system and its environment, jointly subjected to a unitary action, and an interaction-free reference system. It has been shown that coherent information between the initially correlated open system and reference system is conserved in the transmission stage of any quantum communication process, provided that the tripartite input is any pure Markov state and the overall evolution preserves its form. This conservation constitutes the necessary and sufficient condition for accomplishment of perfect error correction by a recovery channel even in the presence of initial system-environment correlations. Explicit expressions of the recovery operators and examples of the joint unitary evolution preserving the form of inputs are given for all classes of pure Markov states.
Acquiring Labor
Authors: Ouimet Paige , Zarutskie Rebecca
Published: August 2020

We present evidence that some firms pursue mergers with an objective of acquiring and retaining the target firm’s employees. We identify such target firms by the language used to describe employees in their 10-K statements, focusing on references to “skilled” employees. We find a positive correlation between the use of the word “skilled” and post-merger employment outcomes. Moreover, we find that it is the target employees most valuable to the firm that are relatively more likely to be retained following an acquiring-labor-motivated acquisition. Acquirers appear to retain the high value employees in acquiring-labor-motivated acquisitions by providing these workers with relatively greater wage increases.
Software Needs Seatbelts and Airbags
Authors: Berger Emery D.
Published: August 2020

Like death and taxes, buggy code is an unfortunate fact of life. Nearly every program ships with known bugs, and probably all of them end up with bugs that are discovered only post-deployment. There are many reasons for this sad state of affairs.
All Your Database Are Belong to Us
Authors: Meijer Erik
Published: August 2020

In the database world, the raw physical data model is at the center of the universe, and queries freely assume intimate details of the data representation (indexes, statistics, metadata). This closed-world assumption and the resulting lack of abstraction have the pleasant effect of allowing the data to outlive the application. On the other hand, this makes it hard to evolve the underlying model independently from the queries over the model.
The Logic of Logging
Authors: Neville-Neil George
Published: August 2020

I work in a pretty open environment, and by open I mean that many people have the ability to become the root user on our servers so that they can fix things as they break.
überSpark
Authors: Vasudevan Amit , Maniatis Petros , Martins Ruben
Published: August 2020

Today's computing ecosystem, comprising commodity heterogeneous interconnected computing (CHIC) platforms, is increasingly being employed for critical applications, consequently demanding fairly strong end-to-end assurances. However, the generality and system complexity of today's CHIC stack seem to outpace existing tools and methodologies toward provable end-to-end guarantees. This paper describes our on-going research, and presents überSpark, a system architecture that argues for structuring the CHIC stack around Universal Object Abstractions (üobjects), a fundamental system abstraction and building block towards practical and provable end-to-end guarantees.
β-Cell-specific ablation of sirtuin 4 does not affect nutrient-stimulated insulin secretion in mice
Authors: Huynh Frank K. , Peterson Brett S. , Anderson Kristin A. , Lin Zhihong , Coakley Aeowynn J. , Llaguno Fiara M. S. , Nguyen Thi-Tina N. , Campbell Jonathan E. , Stephens Samuel B. , Newgard Christopher B. , Hirschey Matthew D.
Published: August 2020

Sirtuins are a family of proteins that regulate biological processes such as cellular stress and aging by removing posttranslational modifications (PTMs). We recently identified several novel PTMs that can be removed by sirtuin 4 (SIRT4), which is found in mitochondria. We showed that mice with a global loss of SIRT4 [SIRT4-knockout (KO) mice] developed an increase in glucose- and leucine-stimulated insulin secretion, and this was followed by accelerated age-induced glucose intolerance and insulin resistance. Because whole body SIRT4-KO mice had alterations to nutrient-stimulated insulin secretion, we hypothesized that SIRT4 plays a direct role in regulating pancreatic β-cell function. Thus, we tested whether β-cell-specific ablation of SIRT4 would recapitulate the elevated insulin secretion seen in mice with a global loss of SIRT4. Tamoxifen-inducible β-cell-specific SIRT4-KO mice were generated, and their glucose tolerance and glucose- and leucine-stimulated insulin secretion were measured over time. These mice exhibited normal glucose- and leucine-stimulated insulin secretion and maintained normal glucose tolerance even as they aged. Furthermore, 832/13 β-cells with a CRISPR/Cas9n-mediated loss of SIRT4 did not show any alterations in nutrient-stimulated insulin secretion. Despite the fact that whole body SIRT4-KO mice demonstrated an age-induced increase in glucose- and leucine-stimulated insulin secretion, our current data indicate that the loss of SIRT4 specifically in pancreatic β-cells, both in vivo and in vitro, does not have a significant impact on nutrient-stimulated insulin secretion. These data suggest that SIRT4 controls nutrient-stimulated insulin secretion during aging by acting on tissues external to the β-cell, which warrants further study.
Transcriptomic signature of fasting in human adipose tissue
Authors: Defour Merel , Michielsen Charlotte C. J. R. , O’Donovan Shauna D. , Afman Lydia A. , Kersten Sander
Published: August 2020

Little is known about gene regulation by fasting in human adipose tissue. Accordingly, the objective of this study was to investigate the effects of fasting on adipose tissue gene expression in humans. To that end, subcutaneous adipose tissue biopsies were collected from 11 volunteers 2 and 26 h after consumption of a standardized meal. For comparison, epididymal adipose tissue was collected from C57Bl/6J mice in the ab libitum-fed state and after a 16 h fast. The timing of sampling adipose tissue roughly corresponds with the near depletion of liver glycogen. Transcriptome analysis was carried out using Affymetrix microarrays. We found that, 1) fasting downregulated numerous metabolic pathways in human adipose tissue, including triglyceride and fatty acid synthesis, glycolysis and glycogen synthesis, TCA cycle, oxidative phosphorylation, mitochondrial translation, and insulin signaling; 2) fasting downregulated genes involved in proteasomal degradation in human adipose tissue; 3) fasting had much less pronounced effects on the adipose tissue transcriptome in humans than mice; 4) although major overlap in fasting-induced gene regulation was observed between human and mouse adipose tissue, many genes were differentially regulated in the two species, including genes involved in insulin signaling ( PRKAG2, PFKFB3), PPAR signaling ( PPARG, ACSL1, HMGCS2, SLC22A5, ACOT1), glycogen metabolism ( PCK1, PYGB), and lipid droplets ( PLIN1, PNPLA2, CIDEA, CIDEC). In conclusion, although numerous genes and pathways are regulated similarly by fasting in human and mouse adipose tissue, many genes show very distinct responses to fasting in humans and mice. Our data provide a useful resource to study adipose tissue function during fasting.
Prevention of Periodontal Pocket Formation after Mandibular Third Molar Extraction Using Dentin Autologous Graft: A Split Mouth Case Report
Authors: De Biase Alberto , Mazzucchi Giulia , Di Nardo Dario , Lollobrigida Marco , Serafini Giorgio , Testarelli Luca
Published: August 2020

Surgical extraction of the third molar can often result in the development of a periodontal pocket distal to the second molar that could delay the healing, and the socket could be colonized by bacteria and lead to secondary abscesses, or it may cause mobility or hypersensitivity. The aim of this case report is to assess the efficacy of a dentin autograft in the prevention of periodontal dehiscences after the surgical extraction of the third molar, obtained by the immediate grinding of the extracted tooth. A healthy 18-year-old male patient underwent surgery of both impacted mandibular molars: right postextractive socket was filled with grinded dentin; then, the left one was filled with fibrin sponge. The patient was followed up for six months, and clinical and radiographic assessment were performed: measurements of plaque index (PI), bleeding on probing (BOP), gingival index (GI), clinical attachment level (CAL), and probing pocket depth (PPD) were done before surgery and repeated at 90 and 180 days after the extractions. Measurements made at six months after the surgery revealed that the grafted site was characterized by a minor depth of the pocket if compared with the nongrafted site, with no clinical/radiographic signs of complications.
A Deep Reinforcement Learning Approach to the Optimization of Data Center Task Scheduling
Authors: Che Haiying , Bai Zixing , Zuo Rong , Li Honglei
Published: August 2020

With more businesses are running online, the scale of data centers is increasing dramatically. The task-scheduling operation with traditional heuristic algorithms is facing the challenges of uncertainty and complexity of the data center environment. It is urgent to use new technology to optimize the task scheduling to ensure the efficient task execution. This study aimed at building a new scheduling model with deep reinforcement learning algorithm, which integrated the task scheduling with resource-utilization optimization. The proposed scheduling model was trained, tested, and compared with classical scheduling algorithms on real data center datasets in experiments to show the effectiveness and efficiency. The experiment report showed that the proposed algorithm worked better than the compared classical algorithms in the key performance metrics: average delay time of tasks, task distribution in different delay time levels, and task congestion degree.
PD-1 Inhibitor Therapy in a Patient with Preexisting P-ANCA Vasculitis: A Case Report and Review of the Literature
Authors: Ramos Amanda , del Carmen Marcela , Yeku Oladapo
Published: August 2020

Background. Recurrent endometrial cancer after definitive therapy is a lethal disease. Recently, immune checkpoint inhibitors (ICI) have improved the management of mismatch repair-deficient (MSI-H) endometrial cancer. Autoimmune side effects are known to occur with ICI. As a result, patients with preexisting autoimmune diseases are excluded from studies involving these drugs. This has led to challenges in clinical practice regarding the use of ICI in otherwise eligible patients with underlying autoimmune disease. Case Presentation. We present the case of an 81-year-old woman with an underlying autoimmune vasculitis and recurrent, metastatic endometrial adenocarcinoma with microsatellite instability, who was treated with an immune checkpoint inhibitor. This patient received pembrolizumab, an immune checkpoint inhibitor that targets the programmed cell death-1 immune checkpoint. Ultimately, she was treated for 4 months with pembrolizumab and benefited from stable disease during this period. She remained asymptomatic from her underlying autoimmune P-ANCA vasculitis. A review of the scientific literature reveals several cases of the successful use of immune checkpoint inhibitors in patients with autoimmune diseases, including systemic lupus erythematosus, rheumatoid arthritis, and inflammatory bowel disease. Conclusion. This is one of the first reports of a patient with an underlying autoimmune vasculitis successfully treated with an immune checkpoint inhibitor without exacerbating her underlying autoimmune condition. Carefully selected patients with underlying autoimmune vasculitis can be safely treated with ICI.
Static Output Feedback Predictive Control for Cyber-Physical System under Denial of Service Attacks
Authors: Wang Zhiwen , Wang Xiaoping , Sun Hongtao , Xin Peng
Published: August 2020

This paper addresses the static output feedback predictive (SOFP) control problem with cyber-physical system (CPS) subject to Denial-of-Service (DoS) attacks. The effects of DoS attacks are reasonably assumed to the bounded consecutive packet dropouts by considering the energy constraints of an attacker. Then, a novel predictive control sequence, in which only the latest successfully received output is employed, is designed to compensate such packet dropouts caused by DoS attacks. Furthermore, the stability criterion and predictive control design are carefully derived by using the switching Lyapunov functional approach and linear matrix inequality. Compared with the previous works, the proposed predictive control strategy can compensate arbitrary packet dropouts under DoS attacks while only the latest successfully received output is available. At last, a simulation example illustrates the effectiveness of the SOFP control strategy.
Basic Framework and Main Methods of Uncertainty Quantification
Authors: Zhang Juan , Yin Junping , Wang Ruili
Published: August 2020

Since 2000, the research of uncertainty quantification (UQ) has been successfully applied in many fields and has been highly valued and strongly supported by academia and industry. This review firstly discusses the sources and the types of uncertainties and gives an overall discussion on the goal, practical significance, and basic framework of the research of UQ. Then, the core ideas and typical methods of several important UQ processes are introduced, including sensitivity analysis, uncertainty propagation, model calibration, Bayesian inference, experimental design, surrogate model, and model uncertainty analysis.
The Central Role and Possible Mechanisms of Bacterial DNAs in Sepsis Development
Authors: Cheng Zhenxing , Abrams Simon T. , Austin James , Toh Julien , Wang Susan Siyu , Wang Zhi , Yu Qian , Yu Weiping , Toh Cheng Hock , Wang Guozheng
Published: August 2020

The pathological roles of bacterial DNA have been documented many decades ago. Bacterial DNAs are different from mammalian DNAs; the latter are heavily methylated. Mammalian cells have sensors such as TLR-9 to sense the DNAs with nonmethylated CpGs and distinguish them from host DNAs with methylated CpGs. Further investigation has identified many other types of DNA sensors distributed in a variety of cellular compartments. These sensors not only sense foreign DNAs, including bacterial and viral DNAs, but also sense damaged DNAs from the host cells. The major downstream signalling pathways includeTLR-9-MyD88-IKKa-IRF-7/NF-κB pathways to increase IFN/proinflammatory cytokine production, STING-TBK1-IRF3 pathway to increase IFN-beta, and AIM2-ASC-caspas-1 pathway to release IL-1beta. The major outcome is to activate host immune response by inducing cytokine production. In this review, we focus on the roles and potential mechanisms of DNA sensors and downstream pathways in sepsis. Although bacterial DNAs play important roles in sepsis development, bacterial DNAs alone are unable to cause severe disease nor lead to death. Priming animals with bacterial DNAs facilitate other pathological factors, such as LPS and other virulent factors, to induce severe disease and lethality. We also discuss compartmental distribution of DNA sensors and pathological significance as well as the transport of extracellular DNAs into cells. Understanding the roles of DNA sensors and signal pathways will pave the way for novel therapeutic strategies in many diseases, particularly in sepsis.
Chinese Herbal Formula Xuefu Zhuyu for Stable Angina (CheruSA): Study Protocol for a Multicenter Randomized Controlled Trial
Authors: Liao Shaojun , Zhang Zhe , Li Geng , Zhou Li , Jiang Junwen , Zhang Ni , Wang Yang , Du Yi , Wen Zehuai
Published: August 2020

Introduction. Stable angina (SA) in coronary heart disease is a common ischemic heart disease endangering the patient’s quality of life and longevity. Clinical trials have demonstrated that the Chinese herbal formula Xuefu Zhuyu (XFZY) has benefits for SA patients. However, there remains a lack of high‐quality evidence to support clinical decision‐making. Therefore, we designed a randomized controlled trial (RCT) to evaluate the efficacy and safety of XFZY for SA. Methods and Analysis. This multicenter, double‐blinded RCT will be conducted in China. 152 eligible participants will be randomly assigned to either an XFZY group or a control group at a 1 : 1 ratio. Participants in the XFZY group will receive XFZY plus routine care, while those in the control group will receive placebo plus routine care. The study period is 26 weeks, including a 2‐week run‐in period, a 12‐week treatment period, and a 12‐week follow‐up. The primary outcome is the change in visual analogue scale score for angina pain intensity from baseline to 12 weeks. The secondary outcomes are the angina attack frequency and duration, the nitroglycerin dosage consumed, the Canadian Cardiovascular Society grading of effort angina, the Seattle Angina Questionnaire, the EuroQol‐5‐Dimensions‐5‐Level, the incidence of major adverse cardiac events, health cost evaluation, and overall assessment for study drugs. Ethics and Dissemination. The study has been approved by the ethics committee of Guangdong Provincial Hospital of Chinese Medicine (approval no. BF2019‐175‐01). Results will be submitted for publication in peer‐reviewed journals and disseminated at scientific conferences. This trial is registered with ChiCTR1900026899, registered on 26 October 2019.
A Four-Zone Model and Nonlinear Dynamic Analysis of Solution Multiplicity of Buoyancy Ventilation in Underground Building
Authors: Wang Yuxing , Wei Chunyu
Published: August 2020

The solution multiplicity of natural ventilation in buildings is very important to personnel safety and ventilation design. In this paper, a four-zone model of buoyancy ventilation in typical underground building is proposed. The underground structure is divided to four zones, a differential equation is established in each zone, and therefore, there are four differential equations in the underground structure. By solving and analyzing the equilibrium points and characteristic roots of the differential equations, we analyze the stability of three scenarios and obtain the criterions to determine the stability and existence of solutions for two scenarios. According to these criterions, the multiple steady states of buoyancy ventilation in any four-zone underground buildings for different stack height ratios and the strength ratios of the heat sources can be obtained. These criteria can be used to design buoyancy ventilation or natural exhaust ventilation systems in underground buildings. Compared with the two-zone model in (Liu et al. 2020), the results of the proposed four-zone model are more consistent with CFD results in (Liu et al. 2018). In addition, the results of proposed four-zone model are more specific and more detailed in the unstable equilibrium point interval. We find that the unstable equilibrium point interval is divided into two different subintervals corresponding to the saddle point of index 2 and the saddle focal equilibrium point of index 2, respectively. Finally, the phase portraits and vector field diagrams for the two scenarios are given.
Number of Remaining Teeth and Its Association with Educational Level in Chilean Adults: Data from the National Health Survey 2016-2017
Authors: Margozzini Paula , Berrios Rodrigo , García-Huidobro Rosario , Véliz Claudia , Valle Carolina del , Vargas Juan Pablo , Padilla Oslando , Ortuño Duniel
Published: August 2020

Introduction. Several population studies have addressed oral health inequalities. Edentulism, functional dentition, and number of remaining teeth have been associated with different socioeconomic level measurements. The aim of this study was to evaluate the association between educational level and tooth loss in the Chilean population aged 15 years and above, based on the 2016-2017 National Health Survey (ENS 2016-2017). Material and Methods. The sample for this cross-sectional study comprised 5473 subjects. The main independent variable was educational level (LEL: low, MEL: medium, and HEL: high). To measure tooth loss, we considered the variables number of remaining teeth, edentulism, and functional dentition. We used logistic regressions to assess the condition of dentition according to the subject’s EL. As to the number of teeth variable, linear regressions were conducted. The analyses were carried out considering the complex sampling design in SPSS 24.0. Results. When comparing LEL subjects with HEL subjects, the adjusted difference in number of remaining teeth was 3.11 for the maxilla and 1.72 for the mandible. An individual with LEL had a 7.51 [3.50–16.10] and 6.06 [2.68–13.68] times higher risk of upper edentulism and lower edentulism than a HEL individual, respectively. Regarding functional dentition, the adjusted OR in HEL subjects was 13.33 [8.02–22.15] and in MEL subjects was 2.81 [2.03–3.87], compared to LEL results. Conclusions. LEL was associated with a significant tooth loss in the Chilean population. Subjects with LEL obtained a lower mean of number of remaining teeth and higher prevalence of edentulism and nonfunctional dentition.
An Adolescent with a Rare De Novo Distal Trisomy 6p and Distal Monosomy 6q Chromosomal Combination
Authors: Peterman Leia A. , Vance Gail H. , Conboy Erin E. , Anderson Katelynn , Weaver David D.
Published: August 2020

We report on a 12-year-old female with both a partial duplication and deletion involving chromosome 6. The duplication involves 6p25.3p24.3 (7.585 Mb) while the deletion includes 6q27q27 (6.244 Mb). This chromosomal abnormality is also described as distal trisomy 6p and distal monosomy 6q. The patient has a Chiari II malformation, hydrocephalus, agenesis of the corpus callosum, microcephaly, bilateral renal duplicated collecting system, scoliosis, and myelomeningocele associated with a neurogenic bladder and bladder reflux. Additional features have included seizures, feeding dysfunction, failure to thrive, sleep apnea, global developmental delay, intellectual disability, and absent speech. To our knowledge, our report is just the sixth case in the literature with concomitant distal 6p duplication and distal 6q deletion. Although a majority of chromosomal duplication-deletion cases have resulted from a parental pericentric inversion, the parents of our case have normal chromosomes. This is the first reported de novo case of distal 6p duplication and distal 6q deletion. Alternate explanations for the origin of the patient’s chromosome abnormalities include parental gonadal mosaicism, nonallelic homologous recombination, or potentially intrachromosomal transposition of the telomeres of chromosome 6. Nonpaternity was considered but ruled out by whole exome sequencing analysis.
Targeting Obesity-Induced Macrophages during Preneoplastic Growth Promotes Mammary Epithelial Stem/Progenitor Activity, DNA Damage, and Tumor Formation
Authors: Chamberlin Tamara , Clack Megan , Silvers Caylee , Kuziel Genevra , Thompson Victoria , Johnson Haley , Arendt Lisa M.
Published: August 2020

Obesity enhances breast cancer risk in postmenopausal women and premenopausal women with genetic or familial risk factors. We have shown previously that within breast tissue, obesity increases macrophage-driven inflammation and promotes expansion of luminal epithelial cell populations that are hypothesized to be the cells of origin for the most common subtypes of breast cancer. However, it is not clear how these changes within the microenvironment of the breast alter cancer risk and tumor growth. Using a high-fat diet to induce obesity, we examined preneoplastic changes associated with epithelial cell-specific loss of Trp53. Obesity significantly enhanced the incidence of tumors of diverse histotypes and increased stromal cells within the tumor microenvironment. Obesity also promoted the growth of preneoplastic lesions containing elevated numbers of luminal epithelial progenitor cells, which were surrounded by macrophages. To understand how macrophage-driven inflammation due to obesity enhances tumor formation, mice were treated with IgG or anti-F4/80 antibodies to deplete macrophages during preneoplastic growth. Unexpectedly, depletion of macrophages in obese mice enhanced mammary epithelial cell stem/progenitor activity, elevated expression of estrogen receptor alpha, and increased DNA damage in cells. Together, these results suggest that in obesity, macrophages reduce epithelial cells with DNA damage, which may limit the progression of preneoplastic breast lesions, and uncovers complex macrophage function within the evolving tumor microenvironment. Understanding how obesity alters the function of macrophages during tumor formation may lead to chemoprevention options for at-risk obese women.

Significance:

Understanding how obesity impacts early tumor growth and response to macrophage-targeted therapies may improve therapeutics for obese patients with breast cancer and identify patient populations that would benefit from macrophage-targeted therapies.
Heritable Susceptibility to Breast Cancer among African-American Women in the Detroit Research on Cancer Survivors Study
Authors: Purrington Kristen S. , Raychaudhuri Sreejata , Simon Michael S. , Clark Julie , Ratliff Valerie , Dyson Gregory , Craig Douglas B. , Boerner Julie L. , Beebe-Dimmer Jennifer L. , Schwartz Ann G.
Published: August 2020

Background:

African-American women have high rates of breast cancer associated with hereditary features. However, no studies have reported the prevalence of inherited variation across all genes known to be breast cancer risk factors among African-American patients with breast cancer not selected for high-risk characteristics.

Methods:

We evaluated 182 African-American women diagnosed with invasive breast cancer in metropolitan Detroit via targeted capture and multiplex sequencing of 13 well-established breast cancer risk genes and five suggested breast cancer risk genes.

Results:

We identified 24 pathogenic variants in 23 women [12.6%; 95% confidence interval (CI), 8.2%–18.4%] and five genes (BRCA2, BRCA1, ATM, RAD50, CDH1). BRCA1 and BRCA2 accounted for 58.3% of all pathogenic variants. An additional six pathogenic variants were found in suggested breast cancer risk genes (MSH6, MUTYH, NF1, BRIP1).

Conclusions:

The prevalence of germline pathogenic variants is relatively high among African-American patients with breast cancer unselected for high-risk characteristics across a broad spectrum of genes.

Impact:

This study helps to define the genomic landscape of breast cancer susceptibility in African-American women who could benefit from enhanced surveillance and screening.
Maternal Mental Disorders before Delivery and the Risk of Dental Caries in Children
Authors: Auger Nathalie , Low Nancy , Lee Gaeun , Lo Ernest , Nicolau Belinda
Published: August 2020

Prevention of childhood caries is an ongoing public health challenge, but the possibility of an association with maternal mental disorders has received limited attention. We estimated the extent to which maternal mental disorders are associated with an increased risk of hospitalization due to dental caries. We conducted a longitudinal cohort study of 790,758 infants born in Quebec, Canada between 2006 and 2016, with follow-up extending to 2018. We identified women with mental disorders before or during pregnancy and computed the incidence of dental caries in their children. We estimated HR and 95% CI for the association of maternal mental disorders with the risk of dental caries, adjusted for personal characteristics. Infants of women with mental disorders before or during pregnancy had a higher incidence of dental caries compared to children of women with no mental disorder (56.1 vs. 27.2 per 10,000 person-years). Maternal stress and anxiety disorders (HR = 1.73; 95% CI 1.60–1.86), depression (HR = 1.81; 95% CI 1.60–2.03), schizophrenia and delusional disorders (HR = 1.69; 95% CI 1.29–2.22), and personality disorders (HR = 1.89; 95% CI 1.70–2.11) were associated with the risk of dental caries. The associations were present throughout childhood, including after 7 years (HR = 1.65; 95% CI 1.38–1.96). Maternal mental disorders were associated with caries of the enamel, dentin, and cementum and caries that reached the dental pulp. Maternal mental disorders before or during pregnancy, especially stress and anxiety, depression, schizophrenia, and personality disorders, are associated with the risk of childhood caries. Women with a history of mental disorders may benefit from enhanced strategies for prevention of dental caries in their children.
Topical Vitamin D Receptor Antagonist/Partial-Agonist Treatment Induces Epidermal Hyperproliferation via RARγ Signaling Pathways
Authors: Lucas Renata , Mihály Johanna , Gericke Janine , de Lera Angel R. , Alvarez Susana , Veleczki Zsuzsanna , Törőcsik Dániel , Rühl Ralph
Published: August 2020

Vitamin D and A derivatives are well-known endogenous substances responsible for skin homeostasis. In this study we topically treated shaved mouse skin with a vitamin D agonist (MC903) or vitamin D antagonist/partial agonist (ZK159222) and compared the changes with acetone (control treatment) treatment for 14 days. Topical treatment with ZK159222 resulted in increased expression of genes involved in retinoic acid synthesis, increased retinoic acid concentrations and increased expression of retinoid target genes. Clustering the altered genes revealed that heparin-binding epidermal growth factor-like growth factor, the main driver of epidermal hyperproliferation, was increased via RARγ-mediated pathways, while other clusters of genes were mainly decreased which were comparable to the changes seen upon activation of the RARα-mediated pathways. In summary, we conclude that epidermal hyperproliferation of mouse skin in response to a topically administered vitamin D receptor antagonist/partial agonist (ZK159222) is induced via increased retinoic acid synthesis, retinoic acid levels and increased RARγ-mediated pathways.
The Management of Myelomeningocele Study: Short-Term Neonatal Outcomes
Authors: Rintoul Natalie E. , Keller Roberta L. , Walsh William F. , Burrows Pamela K. , Thom Elizabeth A. , Kallan Michael J. , Howell Lori J. , Adzick N. Scott ,   for the MOMS Investigators
Published: August 2020

Introduction: The Management of Myelomeningocele Study was a multicenter randomized trial to compare prenatal and standard postnatal repair of myelomeningocele (MMC). Neonatal outcome data for 158 of the 183 randomized women were published in The New England Journal of Medicine in 2011. Objective: Neonatal outcomes for the complete trial cohort (N = 183) are presented outlining the similarities with the original report and describing the impact of gestational age as a mediator. Methods: Gestational age, neonatal characteristics at delivery, and outcomes including common complications of prematurity were assessed. Results: Analysis of the complete cohort confirmed the initial findings that prenatal surgery was associated with an increased risk for earlier gestational age at birth. Delivery occurred before 30 weeks of gestation in 11% of neonates that had fetal MMC repair. Adverse pulmonary sequelae were rare in the prenatal surgery group despite an increased rate of oligohydramnios. There was no significant difference in other complications of prematurity including patent ductus arteriosus, sepsis, necrotizing enterocolitis, periventricular leukomalacia, and intraventricular hemorrhage. Conclusion: The benefits of prenatal surgery outweigh the complications of prematurity.
An Acidic Environment Induces APOL1-Associated Mitochondrial Fragmentation
Authors: Li DengFeng , Snipes James A. , Murea Mariana , Molina Anthony J.A. , Divers Jasmin , Freedman Barry I. , Ma Lijun , Petrovic Snezana
Published: August 2020

Background: Apolipoprotein L1 gene (APOL1) G1 and G2 kidney-risk variants (KRVs) cause CKD in African Americans, inducing mitochondrial dysfunction. Modifying factors are required, because a minority of individuals with APOL1 high-risk genotypes develop nephropathy. Given that APOL1 function is pH-sensitive and the pH of the kidney interstitium is <7, we hypothesized the acidic kidney interstitium may facilitate APOL1 KRV-induced mitochondrial dysfunction. Methods: Human embryonic kidney (HEK293) cells conditionally expressing empty vector (EV), APOL1-reference G0, and G1 or G2 KRVs were incubated in media pH 6.8 or 7.4 for 4, 6, or 8 h. Genotype-specific pH effects on mitochondrial length (µm) were assessed using confocal microscopy in live cells and Fiji derivative of ImageJ software with MiNA plug-in. Lower mitochondrial length indicated fragmentation and early dysfunction. Results: After 6 h doxycycline (Dox) induction in pH 6.8 media, G2-expressing cells had shorter mitochondria (6.54 ± 0.40) than cells expressing EV (7.65 ± 0.72, p = 0.02) or G0 (7.46 ± 0.31, p = 0.003). After 8 h Dox induction in pH 6.8 media, both G1- (6.21 ± 0.26) and G2-expressing cells had shorter mitochondria (6.46 ± 0.34) than cells expressing EV (7.13 ± 0.32, p = 0.002 and p = 0.008, respectively) or G0 (7.22 ± 0.45, p = 0.003 and p = 0.01, respectively). Mitochondrial length in cells incubated in pH 7.4 media were comparable after 8 h Dox induction regardless of genotype. APOL1 mRNA expression and cell viability were comparable regardless of pH or genotype after 8 h Dox induction. Conclusion: Acidic pH facilitates early mitochondrial dysfunction induced by APOL1 G1 and G2 KRVs in HEK293 cells. We propose that the acidic kidney interstitium may play a role in APOL1-mediated mitochondrial pathophysiology and nephropathy.
A Educação em museus e os materiais educativos
Authors:   Universidade de São Paulo. Facudade de Educação, Marandino Martha , Monaco Luciana ,   Universidade de São Paulo. Facudade de Educação, Lourenço Marcia F. ,   Universidade de São Paulo. Facudade de Educação, Rodrigues Juliana ,   Universidade de São Paulo. Facudade de Educação, Ricci Fernanda Pardini ,   Universidade de São Paulo. Facudade de Educação
Published: August 2020

Para além das atividades de atendimento ao público nas exposições, de cursos e workshops, os museus – mais especificamente, os educadores dos museus – produzem materiais educativos. E produzem muito! Ao longo dos anos, a elaboração de materiais pelos setores educativos dos museus se ampliou, fazendo com que estes se estruturassem para realizar seu empréstimo e levando os educadores a se empenhar, cada vez mais, na produção de artefatos pedagógicos com a finalidade de divulgar, ensinar conteúdos, entreter e promover acesso ao conhecimento pelos visitantes. Em nossa experiência, nos deparamos com estes materiais o tempo todo, evidenciando essa produção singular desenvolvida pelos educadores dos museus. Esse livro é mais um passo na direção de dar visibilidade a mais uma faceta da educação em museus: os materiais educativos museais! É uma forma de valorizar o trabalho de educadores e educadoras que atuam no cotidiano das ações educativas, elaborando estratégias, propostas e materiais com a intenção de promover uma experiência prazerosa, mas também de aprendizado, para os variados públicos. Esperamos que este exemplar, que compõe a série de livros do GEENF voltados para educadores de museus, professores e interessados no tema, instigue esses profissionais a analisar suas ações educativas, principalmente aquelas voltadas à produção e ao uso de materiais educativos. Em especial, desejamos que esta publicação estimule os museus a produzirem mais e melhores materiais educativos para qualificar ainda mais sua atuação junto aos seus diferentes públicos.
Um olhar sobre a literatura comparada no Brasil
Authors:   Universidade de São Paulo. Instituto de Estudos Brasileiros, Nitrini Sandra
Published: August 2020

A partir da hipótese inicial, a autora chama a atenção para a relação fundadora do comparatismo com as cadeiras de literaturas estrangeiras (principalmente a que ela mais de perto conhece: a de Literatura Francesa na USP) e com a de literatura nacional, em tradução para outras línguas e em relação com outras literaturas. Depois, faz um percurso em que concilia dados históricos relevantes (como a criação da Abralic) com observações sobre a criação de um discurso comparatista brasileiro, ressaltando alguns nomes importantes do passado, como Antonio Candido e Silviano Santiago, e do presente, como João Cezar de Castro Rocha. Finalmente, com o intuito de fornecer evidências empíricas sobre o comparatismo, a professora Nitrini apresenta uma amostra do que se faz nos programas de pós-graduação em nosso país.
Altered Cardiovascular Defense to Hypotensive Stress in the Chronically Hypoxic Fetus
Authors: Allison Beth J. , Brain Kirsty L. , Niu Youguo , Kane Andrew D. , Herrera Emilio A. , Thakor Avnesh S. , Botting Kimberley J. , Cross Christine M. , Itani Nozomi , Shaw Caroline J. , Skeffington Katie L. , Beck Chritian , Giussani Dino A.
Published: August 2020

The hypoxic fetus is at greater risk of cardiovascular demise during a challenge, but the reasons behind this are unknown. Clinically, progress has been hampered by the inability to study the human fetus non-invasively for long period of gestation. Using experimental animals, there has also been an inability to induce gestational hypoxia while recording fetal cardiovascular function as the hypoxic pregnancy is occurring. We use novel technology in sheep pregnancy that combines induction of controlled chronic hypoxia with simultaneous, wireless recording of blood pressure and blood flow signals from the fetus. Here, we investigated the cardiovascular defense of the hypoxic fetus to superimposed acute hypotension. Pregnant ewes carrying singleton fetuses surgically prepared with catheters and flow probes were randomly exposed to normoxia or chronic hypoxia from 121±1 days of gestation (term ≈145 days). After 10 days of exposure, fetuses were subjected to acute hypotension via fetal nitroprusside intravenous infusion. Underlying in vivo mechanisms were explored by (1) analyzing fetal cardiac and peripheral vasomotor baroreflex function; (2) measuring the fetal plasma catecholamines; and (3) establishing fetal femoral vasoconstrictor responses to the α
1
-adrenergic agonist phenylephrine. Relative to controls, chronically hypoxic fetal sheep had reversed cardiac and impaired vasomotor baroreflex function, despite similar noradrenaline and greater adrenaline increments in plasma during hypotension. Chronic hypoxia markedly diminished the fetal vasopressor responses to phenylephrine. Therefore, we show that the chronically hypoxic fetus displays markedly different cardiovascular responses to acute hypotension, providing in vivo evidence of mechanisms linking its greater susceptibility to superimposed stress.
Heart Failure and Atrial Fibrillation Modify the Associations of Nocturnal Blood Pressure Dipping Pattern With Mortality in Hemodialysis Patients
Authors: Mayer Christopher C. , Schmaderer Christoph , Loutradis Charalampos , Matschkal Julia , Theodorakopoulou Marrieta , Lorenz Georg , Karpetas Antonios , Angermann Susanne , Bikos Athanasios , Braunisch Matthias C. , Raptis Vasilios , Baumann Marcus , Papagianni Aikaterini , Heemann Uwe , Wassertheurer Siegfried , Sarafidis Pantelis A.
Published: August 2020

Heart failure (HF), hypertension, and abnormal nocturnal blood pressure dipping are highly prevalent in hemodialysis patients. Atrial fibrillation (AF) and HF might be important mediators for the association of abnormal dipping patterns with worse prognosis. Thus, the aim of this study is to investigate the association of dipping with mortality in hemodialysis patients and to assess the influence of AF and HF. In total, 525 hemodialysis patients underwent 24-hour ambulatory blood pressure monitoring. All-cause and cardiovascular mortality served as end points. Patients were categorized according to their systolic dipping pattern (dipper, nondipper, and reverse dipper). Cox regression analysis was performed to determine the association between dipping pattern and study end points with dipping as reference. Subgroup analysis was performed for patients with and without AF or HF. In total, 185 patients with AF or HF and 340 patients without AF or HF were included. During a median follow-up of 37.8 months, 177 patients died; 81 from cardiovascular causes. Nondipping and reverse dipping were significantly associated with all-cause mortality in the whole cohort (nondipper: hazard ratio, 1.95 [1.22–3.14];
P
=0.006; reverse dipper: hazard ratio, 2.31 [1.42–3.76];
P
<0.001) and in patients without AF or HF (nondipper: hazard ratio, 2.78 [1.16–6.66];
P
=0.02; reverse dipper: hazard ratio, 4.48 [1.87–10.71];
P
<0.001) but not in patients with AF or HF. For cardiovascular mortality, associations were again significant in patients without AF or HF and in the whole cohort. The observed associations remained significant after adjustment for possible confounders. This study provides well-powered evidence for the association between abnormal dipping patterns and mortality in hemodialysis patients and suggests that HF or AF modifies this association.