bluuebunny/crossref_metadata_2025 huggingface dataset:
Programmed DNA Elimination in Vertebrates
Authors: Smith Jeramiah J. , Timoshevskiy Vladimir A. , Saraceno Cody
Published: September 2020

Over the last few decades, an increasing number of vertebrate taxa have been identified that undergo programmed genome rearrangement, or programmed DNA loss, during development. In these organisms, the genome of germ cells is often reproducibly different from the genome of all other cells within the body. Although we clearly have not identified all vertebrate taxa that undergo programmed genome loss, the list of species known to undergo loss now represents ∼10% of vertebrate species, including several basally diverging lineages. Recent studies have shed new light on the targets and mechanisms of DNA loss and their association with canonical modes of DNA silencing. Ultimately, expansion of these studies into a larger collection of taxa will aid in reconstructing patterns of shared/independent ancestry of programmed DNA loss in the vertebrate lineage, as well as more recent evolutionary events that have shaped the structure and content of eliminated DNA.
Glucagon-like peptide-1 alleviates diabetic kidney disease through activation of autophagy by regulating AMP-activated protein kinase-mammalian target of rapamycin pathway
Authors: Yang Shuangli , Lin Chuman , Zhuo Xiaoyun , Wang Jiyu , Rao Shitao , Xu Wen , Cheng Yanzhen , Yang Li
Published: September 2020

Glucagon-like peptide-1 (GLP-1) is a novel antidiabetic agent used in clinical practice. Recently, it was reported to exert a renoprotective effect in the human kidney-2 cells and kidneys of diabetic rats, which was induced by one type of GLP-1 analog, liraglutide, in the presence of high glucose. However, most of the previous findings mainly focused on its indirect effect in inhibiting the advanced glycation end products. Here, besides glycemic control, we also demonstrated a stimulatory role of liraglutide in promoting autophagy and relieving oxidative stress in Zucker diabetic fatty rats. The renoprotective effect of liraglutide has been demonstrated by significantly decreasing urinary albumin ( P < 0.01) and ameliorating renal pathological changes ( P < 0.001) in vivo. Besides that, proliferation of human epithelial kidney cell line HKC-8 and human embryonic kidney-293 cells has increased after treating with exendin-4, a GLP-1 receptor (GLP-1R) agonist. Moreover, GLP-1 could positively improve the progression of autophagy in vivo and in vitro through regulating the autophagy-related protein light chain 3 and p62 via AMP-activated protein kinase (AMPK)-mammalian target of rapamycin (mTOR) signaling pathway. Simultaneously, it could reverse NF-erythroid 2-related factor 2 (NRF2) translocation into the nuclei and suppress oxidative stress. In terms of mechanism, the renoprotective effect of GLP-1 would be exerted via the GLP-1R-AMPK-mTOR-autophagy-reactive oxygen species signaling axis. The present study not only illustrates the renoprotective effect of GLP-1 in diabetic kidney disease (DKD) rats, but also for the first time elucidates the underlying mechanism that is independent of controlling glucose, which implies that GLP-1 might be a novel therapeutic strategy for the prevention and treatment of DKD.
Mitochondria-associated ER membranes in glucose homeostasis and insulin resistance
Authors: Townsend Logan K. , Brunetta Henver S. , Mori Marcelo A. S.
Published: September 2020

Obesity and insulin resistance (IR) are associated with endoplasmic reticulum (ER) stress and mitochondrial dysfunction in several tissues. Although for many years mitochondrial and ER function were studied separately, these organelles also connect to produce interdependent functions. Communication occurs at mitochondria-associated ER membranes (MAMs) and regulates lipid and calcium homeostasis, apoptosis, and the exchange of adenine nucleotides, among other things. Recent evidence suggests that MAMs contribute to organelle, cellular, and systemic metabolism. In obesity and IR models, metabolic tissues such as the liver, skeletal muscle, pancreas, and adipose tissue present alterations in MAM structure or function. The purpose of this mini review is to highlight the MAM disruptions that occur in each tissue during obesity and IR and its relationship with glucose homeostasis and IR. We also discuss the current controversy that surrounds MAMs’ role in the development of IR.
Microcirculatory model predicts blood flow and autoregulation range in the human retina: in vivo investigation with laser speckle flowgraphy
Authors: Pappelis Konstantinos , Choritz Lars , Jansonius Nomdo M.
Published: September 2020

We describe and test a new approach to quantify retinal blood flow, based on standard clinical examinations and imaging techniques, linked together with a physiological model. We use these findings to generate individualized estimates of the autoregulation range. We provide evidence that healthy subjects are closer to the lower autoregulation limit than thought before. This suggests that some retinas are less prepared to withstand hypoperfusion, even after small intraocular pressure rises or blood pressure drops.
Climate Comfort Evaluation of National 5A TouristAttractions in the Mainland of China Based on Universal Thermal Climate Index
Authors: Hua Lei , Zhang Hailin , Liu Xiuyun , Yang Xiufeng , Duan He , Wu Tieniu , Nastos Panagiotis
Published: September 2020

Based on the daily climate data from 839 meteorological stations covering the 2014–2017 period in the mainland of China, the Universal Thermal Climate Indices (UTCI) were calculated and the UTCI of 247 national 5A tourist attractions in the mainland of China are obtained with ordinary kriging interpolation method. Then, a spatial analysis of all the attractions was carried out based on UTCI. The results showed that the mainland of China’s annual average UTCI is generally distributed as strip-belts along a latitudinal direction and the climate comfort level gradually decreases from south to north. Significant regional differences in climate comfort results are obtained between the southeast coastal areas and the northwest inland. It was found that the number of attractions with the best climate comfort level is relatively high in spring and autumn while it is less in summer and winter. Considering the climate comfort levels, the attractions are grouped into five categories of “comfortable during spring and autumn,” “comfortable during winter,” “comfortable during spring, autumn, and winter,” “comfortable during spring, summer, and autumn,” and “uncomfortable during the four seasons” to carry out the study for determining the most convenient period of the year in terms of climate comfort.
Dipteran Carboxymethyl Chitosan as an Inexhaustible Derivative with a Potential Antiproliferative Activity in Hepatocellular Carcinoma Cells
Authors: Abdel Rahman Rana M. , Ghaffar Hedayat Abdel , Alkhuriji Afrah F. , Khalil Mahmoud I. , Amaly Noha , El-Kott Attalla F. , Sultan Ahmed S.
Published: September 2020

Traditional folk therapies indicate that insects have diverse medicinal potentials. However, the therapeutic application of insect chitosan and its derivatives has not been explored. To investigate the application of chitosan and its derivatives, the carboxymethyl derivative of chitosan (CM‐Ch) was extracted from two dipteran larvae species, Chrysomya albiceps and Sarcophaga aegyptiaca. The degree of deacetylation (DD) and CM‐Ch functional groups were validated using Fourier‐transform infrared (FTIR) spectroscopy analysis and proton nuclear magnetic resonance spectroscopy (1H NMR), respectively. The molecular weight was estimated using MALDI‐TOF MS analysis. The effect of CM‐Ch on the morphology and proliferation of human liver HepG2 cancer cells was assessed. IC50 of CM‐Ch induced significant growth‐inhibitory effects in HepG2 cells. CM‐Ch treatment altered the morphology of HepG2 in a dose‐dependent manner and induced apoptosis in a caspase‐dependent manner. CM‐Ch treatment showed no signs of toxicity, and no alterations in liver and kidney biochemical markers were observed in albino rats. A CM‐Ch derivative from commercial crustacean chitosan was used to assess the efficacy of the insect‐derived CM‐Ch. The data presented here introduce insect CM‐Ch as a promising, inexhaustible, safe derivative of chitosan with antitumor potential in liver cancer. This is the first report highlighting the anticancer activity of insect CM‐Ch in hepatocellular carcinoma cells.
Effects of Mulch Type, Plant Cultivar, and Insecticide Use on Sweet Potato Whitefly Population in Chili Pepper
Authors: Nasruddin Andi , Agus Nurariaty , Saubil Alam , Jumardi Jumardi , Rasyid Burhanuddin , Siriniang Andry , Nasruddin Andi Dirham , Firdaus Firdaus , Said Ahwiyah Ekawaty , Kershaw David B.
Published: September 2020

One of the most devastating pests of chili pepper is the sweet potato whitefly (SPW), Bemisia tabaci (Gennadius) (Hemiptera: Aleyrodidae). It sucks plant sap, emits honeydew on which sooty mold fungi grow, and transmits the pepper yellow leaf curl Indonesia virus (PepYLCIV), the most damaging viral disease of chili in Indonesia. Farmers rely mainly on insecticide to control the insect with two to three sprays in a week. To reduce the insecticide use, an integrated approach needs to be developed. Therefore, the current study evaluated the effectiveness of the integration of reflective mulch, host plant resistance, and insecticide use for managing the sweet potato whitefly on the chili pepper. In 2018, a complete randomized block design was used in three separate trials to assess the effects of mulch, cultivar, or insecticide application frequency on the numbers of whitefly eggs, nymphs, and adults. In 2019, a split-split plot design was used to evaluate the effects of the integration of mulch, cultivar, and insecticide application frequency on the numbers of whitefly eggs, nymphs, and adults. The results showed that the reflective silver mulch had significantly lower numbers of whitefly eggs, nymphs, and adults, in comparison to the rice straw mulch and bare ground treatments. Chili plants cv. Bara was more resistant than Bhaskara against B. tabaci in the field; however, in the no-choice trial, no significant difference was detected between both cultivars. Insecticide applications twice per week and once per week were equally effective in controlling the whitefly on the susceptible cultivar (Bhaskara). Overall, the integration of reflective mulch, resistant cultivar, and insecticide application every two weeks effectively suppressed B. tabaci populations on the chili pepper. This approach could substantially reduce the number of insecticide applications from twice per week (commonly practiced by chili farmers in the area) to one application only in two weeks.
Alterations of Gut Microbiota in Type 2 Diabetes Individuals and the Confounding Effect of Antidiabetic Agents
Authors: Almugadam Babiker Saad , Liu Yinhui , Chen Shen-min , Wang Chun-hao , Shao Chen-yi , Ren Bao-wei , Tang Li , Hatziagelaki Erifili
Published: September 2020

Type 2 diabetes is a leading cause of morbidity and a common risk of several disorders. Identifying the microbial ecology changes is essential for disease prediction, therapy, and prevention. Thus, our study is aimed at investigating the intestinal microbiota among healthy and type 2 diabetes individuals and exploring the effect of antidiabetic agents on gut bacterial flora. 24 type 2 diabetes (metformin, glimepiride, and nontherapeutic subgroups;

N
=
8

) and 24 healthy control subjects were enrolled in this study, and intestinal bacterial microbiota was investigated by analyzing V3-V4 regions of 16S rRNA gene sequence. Numerous alterations were observed in the gut microbial community of diabetic individuals. These changes were characterized by a significant lowered abundance of Faecalibacterium, Fusobacterium, Dialister, and Elusimicrobium in the nontherapeutic subgroup compared to the healthy control group. Likewise, correlation analysis showed a substantial decline in gut microbiota richness and diversity with the duration of illness. Furthermore, antidiabetic agents restored to some extent the richness and diversity of gut microbiota and improved the abundance of many beneficial bacteria with a significant increase of Methanobrevibacter in the metformin subcategory compared to the nontherapeutic subgroup. In return, they decreased the abundance of some opportunistic pathogens. The findings of this study have added a novel understanding about the pathogenesis of the disease and the mechanisms underlying antidiabetic therapy, which are of potential interest for therapeutic lines and further studies.
Calcaneocuboid and Naviculocuneiform Dislocation: An Unusual Injury of the Midfoot
Authors: Kummer Anne , Crevoisier Xavier , Eudier Antoine , Di Cesare Paul E.
Published: September 2020

Introduction. Midfoot dislocations are rare traumatic injuries. The best known patterns involve the Lisfranc and Chopart joints, although some other types have been described. Dislocations that occur at the level of the naviculocuneiform and calcaneocuboid joints simultaneously represent a very rare configuration of dislocation. Case Presentation. A 34-year-old man sustained a crush injury to his left foot causing a complete dislocation through the naviculocuneiform and calcaneocuboid joints. Immediate closed reduction and percutaneous pinning were performed, followed by open reduction and stabilization of both joints two weeks later. Anatomical reduction was obtained, and the clinical outcome remained satisfactory 10 months after surgery. Discussion. Anatomical reduction is essential to obtain favorable outcomes in traumatic midfoot injuries. An unusual pattern of midfoot dislocation can be treated according to the same principles as those for classical Lisfranc or Chopart injuries.
Multi-Input-Multi-Output Continuous Swept-Sine Vibration Test Realization by Inverse Multistep Prediction Model
Authors: Zheng Wei , Chen Huaihai , Luo Zhengbo , Nassr Amr A.
Published: September 2020

As frequency-varying sine excitations in rotating machines are always emerging during run-ups and shutdowns, the multi-input-multi-output (MIMO) swept-sine test is of utter significance in product validation. At present, swept-sine vibration tests are mostly conducted with frequency-domain methods, where drive spectra are generated and updated by frequency response function (FRF), and drive signals are then generated with sinusoid oscillators. In this paper, a time-domain approach using an inverse system method based on a multistep prediction model is developed to realize the MIMO continuous swept-sine vibration test. First, the multistep prediction model of the original system is estimated in the time domain. Then, the inverse multistep prediction model is derived. After that, this model is truncated to guarantee the robustness of the inverse system and the smoothness of the generated drive signals. At last, the proposed method is validated by a simulation example with a cantilever beam and an actual test by using a three-axis shaker. The results show that the MIMO continuous swept-sine vibration test can be operated effectively by the proposed method.
High Dose of Intravenous Allogeneic Umbilical Cord-Derived Mesenchymal Stem Cells (CLV-100) Infusion Displays Better Immunomodulatory Effect among Healthy Volunteers: A Phase 1 Clinical Study
Authors: Chin Sze-Piaw , Mohd-Shahrizal Mohd-Yusoff , Liyana Mohd-Zuhar , Then Kong Yong , Cheong Soon Keng , Yong Kar Wey
Published: September 2020

Background. Mesenchymal stem cells (MSCs) express growth factors and other cytokines that stimulate repair and control the immune response. MSCs are also immunoprivileged with low risk of rejection. Umbilical cord-derived MSCs (UCMSCs) are particularly attractive as an off-the-shelf allogeneic treatment in emergency medical conditions. We aim to determine the safety and efficacy of intravenous allogeneic infusion of UCMSCs (CLV-100) by Cytopeutics® (Selangor, Malaysia) in healthy volunteers, and to determine the effective dose at which an immunomodulatory effect is observed. Methodology. Umbilical cord samples were collected after delivery of full-term, healthy babies with written consent from both parents. All 3 generations (newborn, parents, and grandparents) were screened for genetic mutations, infections, cancers, and other inherited diseases. Samples were transferred to a certified Good Manufacturing Practice laboratory for processing. Subjects were infused with either low dose (LD, 65 million cells) or high dose (HD, 130 million cells) of CLV-100 and followed up for 6 months. We measured cytokines using ELISA including anti-inflammatory cytokines interleukin 1 receptor antagonist (IL-1RA), interleukin 10 (IL-10), pro-/anti-inflammatory cytokine interleukin 6 (IL-6), and the proinflammatory cytokine tumor necrosis factor-alpha (TNF-α). Results. 11 healthy subjects (LD,

n
=
5

; HD,

n
=
6

; mean age of

55
±
13

years) were recruited. All subjects tolerated the CLV-100 infusion well with no adverse reaction throughout the study especially in vital parameters and routine blood tests. At 6 months, the HD group had significantly higher levels of anti-inflammatory markers IL1-RA (

705
±
160

vs.

306
±
36
 
pg
/
mL

;

p
=
0.02

) and IL-10 (

321
±
27

vs.

251
±
28
 
pg
/
m

L;

p
=
0.02

); and lower levels of proinflammatory marker TNF-α (

74
±
23

vs.

115
±
15
 
pg
/
mL

;

p
=
0.04

) compared to LD group. Conclusion. Allogeneic UCMSCs CLV-100 infusion is safe and well-tolerated in low and high doses. Anti-inflammatory effect is observed with a high-dose infusion.
Relapse and Clinical Characteristics of Patients with Bipolar Disorders in Central Ethiopia: A Cross-Sectional Study
Authors: Belete Habte , Ali Tilahun , Legas Getasew , Pavon Lenin
Published: September 2020

Background. Bipolar disorder is a severe mental illness and has huge morbidity and mortality. Relapse is a challenging treatment failure in patients with mental illness, especially in patients with bipolar which causes high economic and social burdens. In the mental health delivery system, relapse is common and can be defined as becoming ill again after apparent recovery and a worsening condition of psychiatric patients. Due to psychiatric patients that may stop medication on their own in contrary to the advice of mental health professionals, relapse of mood episodes, delayed remission, and residual symptoms usually leads to hospitalization, increased suicide risk, and/or impede psychosocial recover. Therefore, understanding the nature of relapse in patients in low-income countries helps to prevent recurrence and related health care expenses. Objective. The objective of this study was to assess the prevalence and factors associated with relapse among patients with bipolar disorders in central Ethiopia. Method. Facility-based cross-sectional study was conducted from May to June 2015 at Amanuel Mental Specialized Hospital. Relapse was calculated among 400 samples of people with bipolar disorder, and systematic random sampling was used to select the study participants. Oslo’s social support scale and ASSIST were used to identify factors with relapse, and a binary and multivariable logistic regression analysis model was performed to control the confounding factors. Odds ratios (OR) with the corresponding 95% confidence interval (95% CI) were determined to evaluate the strength of association. Results. The prevalence of relapse was 71% among patients with bipolar disorder. The longer morbidity (longer than 5 years) had a higher risk of relapse [

adjusted
 
odd
 
ratio
 

AOR

=
3.91

, 95% confidence interval (CI): 2.44 to 6.27], while good medication adherence found to be a protective factor for relapse [

AOR
=
0.39

, 95% CI: 0.22 to 0.72]. Conclusion. The prevalence of relapse was found pretty high among patients with bipolar disorders (71%). Working on treatment adherence and controlling the psychopathology is important to prevent relapse among bipolar patients.
AZD4320, A Dual Inhibitor of Bcl-2 and Bcl-xL, Induces Tumor Regression in Hematologic Cancer Models without Dose-limiting Thrombocytopenia
Authors: Balachander Srividya B. , Criscione Steven W. , Byth Kate F. , Cidado Justin , Adam Ammar , Lewis Paula , Macintyre Terry , Wen Shenghua , Lawson Deborah , Burke Kathleen , Lubinski Tristan , Tyner Jeffrey W. , Kurtz Stephen E. , McWeeney Shannon K. , Varnes Jeffrey , Diebold R. Bruce , Gero Thomas , Ioannidis Stephanos , Hennessy Edward J. , McCoull William , Saeh Jamal C. , Tabatabai Areya , Tavana Omid , Su Nancy , Schuller Alwin , Garnett Mathew J. , Jaaks Patricia , Coker Elizabeth A. , Gregory Gareth P. , Newbold Andrea , Johnstone Ricky W. , Gangl Eric , Wild Martin , Zinda Michael , Secrist J. Paul , Davies Barry R. , Fawell Stephen E. , Gibbons Francis D.
Published: September 2020

Purpose:

Targeting Bcl-2 family members upregulated in multiple cancers has emerged as an important area of cancer therapeutics. While venetoclax, a Bcl-2–selective inhibitor, has had success in the clinic, another family member, Bcl-xL, has also emerged as an important target and as a mechanism of resistance. Therefore, we developed a dual Bcl-2/Bcl-xL inhibitor that broadens the therapeutic activity while minimizing Bcl-xL–mediated thrombocytopenia.

Experimental Design:

We used structure-based chemistry to design a small-molecule inhibitor of Bcl-2 and Bcl-xL and assessed the activity against in vitro cell lines, patient samples, and in vivo models. We applied pharmacokinetic/pharmacodynamic (PK/PD) modeling to integrate our understanding of on-target activity of the dual inhibitor in tumors and platelets across dose levels and over time.

Results:

We discovered AZD4320, which has nanomolar affinity for Bcl-2 and Bcl-xL, and mechanistically drives cell death through the mitochondrial apoptotic pathway. AZD4320 demonstrates activity in both Bcl-2– and Bcl-xL–dependent hematologic cancer cell lines and enhanced activity in acute myeloid leukemia (AML) patient samples compared with the Bcl-2–selective agent venetoclax. A single intravenous bolus dose of AZD4320 induces tumor regression with transient thrombocytopenia, which recovers in less than a week, suggesting a clinical weekly schedule would enable targeting of Bcl-2/Bcl-xL–dependent tumors without incurring dose-limiting thrombocytopenia. AZD4320 demonstrates monotherapy activity in patient-derived AML and venetoclax-resistant xenograft models.

Conclusions:

AZD4320 is a potent molecule with manageable thrombocytopenia risk to explore the utility of a dual Bcl-2/Bcl-xL inhibitor across a broad range of tumor types with dysregulation of Bcl-2 prosurvival proteins.
A Randomized Placebo Controlled Phase II Trial Evaluating Exemestane with or without Enzalutamide in Patients with Hormone Receptor–Positive Breast Cancer
Authors: Krop Ian , Abramson Vandana , Colleoni Marco , Traina Tiffany , Holmes Frankie , Garcia-Estevez Laura , Hart Lowell , Awada Ahmad , Zamagni Claudio , Morris Patrick G. , Schwartzberg Lee , Chan Stephen , Gucalp Ayca , Biganzoli Laura , Steinberg Joyce , Sica Lorenzo , Trudeau Maureen , Markova Denka , Tarazi Jamal , Zhu Zhou , O'Brien Thomas , Kelly Catherine M. , Winer Eric , Yardley Denise A.
Published: September 2020

Purpose:

To determine whether the androgen receptor (AR) inhibitor, enzalutamide, improves effectiveness of endocrine therapy (ET) in hormone receptor–positive (HR+) breast cancer.

Patients and Methods:

In this phase II trial, patients with HR+/HER2 normal advanced/metastatic breast cancer were randomized 1:1 to exemestane 25 mg with placebo or exemestane 50 mg with enzalutamide 160 mg daily (NCT02007512). Two parallel cohorts enrolled patients with 0 (cohort 1) or 1 (cohort 2) prior ET for advanced disease. Progression-free survival (PFS) was the primary endpoint in the intent-to-treat (ITT) population of each cohort. Biomarkers were evaluated in an exploratory analysis.

Results:

Overall, 247 patients were randomized (cohort 1, n = 127 and cohort 2, n = 120). PFS was not improved in either cohort of the ITT population [HR, 0.82 (95% confidence interval (CI), 0.54–1.26); P = 0.3631 for cohort 1 and HR, 1.02 (95% CI, 0.66–1.59); P = 0.9212 for cohort 2]. In cohort 1, high levels of AR mRNA were associated with greater benefit of enzalutamide (Pinteraction = 0.0048). This effect was particularly apparent in patients with both high levels of AR mRNA and low levels of ESR1 mRNA [HR, 0.24 (95% CI, 0.10–0.60); P = 0.0011]. The most common any grade adverse events in the enzalutamide arms were nausea (39%) in cohort 1 and fatigue (37%) in cohort 2.

Conclusions:

Enzalutamide with exemestane was well tolerated. While PFS was not improved by the addition of enzalutamide to exemestane in an unselected population, ET-naïve patients with high AR mRNA levels, particularly in combination with low ESR1 mRNA levels, may benefit from enzalutamide with exemestane.
Clinical Outcome–Related Mutational Signatures Identified by Integrative Genomic Analysis in Nasopharyngeal Carcinoma
Authors: Dai Wei , Chung Dittman Lai-Shun , Chow Larry Ka-Yue , Yu Valen Zhuoyou , Lei Lisa Chan , Leong Merrin Man-Long , Chan Candy King-Chi , Ko Josephine Mun-Yee , Lung Maria Li
Published: September 2020

Purpose:

Investigation of biological mechanisms underlying genetic alterations in cancer can assist the understanding of etiology and identify the potential prognostic biomarkers.

Experimental Design:

We performed an integrative genomic analysis for a total of 731 nasopharyngeal carcinoma cases from five independent nasopharyngeal carcinoma cohorts to identify the genetic events associated with clinical outcomes.

Results:

In addition to the known mutational signatures associated with aging, APOBEC and mismatch repair (MMR), a new signature for homologous recombination deficiency (BRCAness) was discovered in 64 of 216 (29.6%) cases in the discovery set including three cohorts. This signature appeared more frequently in the recurrent and metastatic tumors and significantly correlated with shorter overall survival (OS) in the primary tumors. Independent prognostic value of MMR and BRCAness signatures was revealed by multivariable Cox analysis after adjustment for clinical parameters and stratification by studies. The cases with both signatures had much worse clinical outcome than those without these signatures [hazard ratio (HR), 12.4; P = 0.002]. This correlation was confirmed in the validation set (HR, 8.9; P = 0.003). The BRCAness signature is highly associated with BRCA2 pathogenic germline or somatic alterations (7.8% vs. 0%; P = 0.002). Targeted sequencing results from a prospective nasopharyngeal carcinoma cohort (N = 402) showed that the cases carrying BRCA2 germline rare variants are more likely to have poor OS and progression-free survival.

Conclusions:

Our study highlights importance of defects of DNA repair machinery in nasopharyngeal carcinoma pathogenesis and their prognostic values for clinical implications. These signatures will be useful for patient stratification to evaluate conventional and new treatment for precision medicine in nasopharyngeal carcinoma.
DNA Methylation Profiling of Premalignant Lesions as a Path to Ovarian Cancer Early Detection
Authors: Ishak Charles A. , De Carvalho Daniel D.
Published: September 2020

Genome-wide DNA methylation profiles of serous tubal intraepithelial carcinomas (STIC) resemble methylation profiles of high-grade serous ovarian carcinomas (HGSOC) more closely than normal fallopian tube epithelium. While STICs and HGSOCs share subsets of common hypermethylated regions, DNA methylation can distinguish STICs from HGSOCs to provide proof-of-principle that DNA methylation can identify HGSOC initiation.

See related article by Pisanic et al., p. 6310
A primeira vez a gente não esquece: conhecendo as drogas experimentadas por estudantes do ensino médio
Authors: Oliveira Eliany Nazaré , Nunes Joyce Mazza , Vasconcelos Maristela Inês Osawa , Viana Lorenna Saraiva , Moreira Roberta Magda Martins , Bezerra Mariana Rodrigues
Published: September 2020

Objetivo: investigar a prevalência do consumo de drogas em escolas de ensino médio de um município referência do estado do Ceará. Método: estudo exploratório descritivo com abordagem quantitativa. A coleta de dados foi realizada no período de março a julho de 2019 com 562 estudantes. Para tanto, utilizou-se o questionário para triagem do uso de álcool, tabaco e outras substâncias. Na análise, realizouse estatística analítica por meio do teste de qui-quadrado. Resultados: em relação as substâncias já experimentadas pelos estudantes, o álcool aparece em maior proporção. Além do álcool, os estudantes também já experimentaram outras substâncias psicoativas, em que maconha, tabaco e hipnóticos ou sedativos tiveram destaque entre as já experimentadas. Em relação aos parâmetros, para todas as substâncias, houve uma proporção variando entre (1,5% a 23,2%) de estudantes necessitando de intervenção breve. Conclusão: estes resultados apresentados contribuem para uma melhor compreensão do fenômeno no que diz respeito às substâncias mais consumidas e padrões de uso nocivo ou dependência, para que possa planejare implementar programas de prevenção primária e secundária no contexto escolar.
Epistemologia discursiva: a semiologia de Saussure e a semiótica de Greimas como terceira via do conhecimento
Authors:   Universidade de São Paulo. Faculdade de Filosofia, Letras e Ciências Humanas, Beividas Waldir
Published: September 2020

O presente estudo é uma sistematização concertada de argumentos aqui dispostos, em uma sequência de capítulos, elaborada de modo a justificar e demonstrar basicamente duas ideias centrais: - a Semiologia de Ferdinand de Saussure e a Semiótica de Algirdas Julien Greimas, que a evoluiu, detêm vocação e estatuto de verdadeira epistemologia discursiva (ou linguageira) do conhecimento do mundo e de si pelo homem, epistemologia de cunho “imanente” à linguagem, em condições de rivalizar com outras epistemologias ambientes; - o conceito de semiocepção, deduzido diretamente da Semiologia, será pleiteado e defendido como a poder rivalizar com o milenar conceito de percepção, com o recente conceito de enação (Francisco Varela) e com demais entendimentos neurobiológicos ou neurocientíficos, atuais, sobre o modo de captação do real do mundo pelo homem, entendimentos que o estudo propõe chamá-los neurocepção.
Almanaque da indumentarista Sophia Jobim: um guia de indumentária, moda, reflexões, imagens e anotações pessoais
Authors:   Universidade de São Paulo, Escola de Comunicações e Artes, Viana Fausto
Published: September 2020

A obra é um almanaque que traz parte da produção da professora de indumentária Sophia Jobim (1904-1968), uma curiosa por natureza e à qual vários temas interessavam. A proposta é apresentar textos pessoais, em verso e prosa, além de um glossário contendo anotações dela sobre temas ligados à indumentária e à moda. O livro também conta com material importante sobre costura e culinária, duas paixões da indumentarista que, juntas, retratavam um estilo de viver e pensar.
Uso corporativo de mídias sociais e o desempenho de mercado
Authors: Giordani Mikaéli da Silva , Lunardi Micheli Aparecida , Klann Roberto Carlos
Published: September 2020

As empresas estão sendo impulsionadas a usar as mídias sociais, entretanto, pouco se sabe sobre o impacto do uso de tais mídias no seu desempenho. Esta pesquisa objetivou verificar a relação entre o uso corporativo de mídias sociais e o desempenho de mercado de empresas brasileiras. Para isso utilizou-se regressão linear múltipla (OLS). O período de análise compreendeu os anos de 2013 a 2017 e a amostra constituiu-se de 225 empresas. O uso das mídias sociais correspondeu a utilização do Twitter para publicação de informações financeiras, enquanto o desempenho de mercado foi mensurado pelo retorno anormal das ações. Os resultados revelaram que o uso corporativo das mídias sociais apresenta relação positiva com o desempenho. Conclui-se que a publicação de tweets sobre informações financeiras pode maximizar os retornos, o que indica que as mídias sociais podem se configurar em mais uma fonte de informações para stakeholders. Como contribuições, os achados evidenciam benefícios reais obtidos com o uso das mídias sociais, ao demonstrar que o uso corporativo do Twitter influencia os participantes do mercado de capitais e, consequentemente, melhora o desempenho de mercado da organização. Tal evidência pode motivar a alta gerência das empresas a fornecer suporte inicial e contínuo para o uso de mídias sociais nas organizações.
Arterial Stiffness Preceding Diabetes
Authors: Zheng Mengyi , Zhang Xinyuan , Chen Shuohua , Song Yongjian , Zhao Quanhui , Gao Xiang , Wu Shouling
Published: September 2020

Rationale:

Previous studies on the relationship between diabetes and arterial stiffness were mostly cross-sectional. A few longitudinal studies focused on one single direction. Whether the association between arterial stiffness and diabetes is bidirectional remains unclear to date.

Objective:

To explore the temporal relationship between arterial stiffness and fasting blood glucose (FBG) status.

Methods and Results:

Included were 14 159 participants of the Kailuan study with assessment of brachial-ankle pulse wave velocity (baPWV) from 2010 to 2015, and free of diabetes, cardiovascular and cerebrovascular diseases, and chronic kidney disease at baseline. FBG and baPWV were repeatedly measured at baseline and follow-ups. Cox proportional hazard regression model was used to estimate hazard ratios and 95% confidence intervals (CIs) of incident diabetes across baseline baPWV groups: <1400 cm/s (ref), 1400≤ baPWV <1800 cm/s, and ≥1800 cm/s. Path analysis was used to analyze the possible temporal causal relationship between baPWV and FBG, among 8956 participants with repeated assessment of baPWV and FBG twice in 2010 to 2017. The mean baseline age of the observed population was 48.3±12.0 years. During mean 3.72 years of follow-up, 979 incident diabetes cases were identified. After adjusting for potential confounders, the hazard ratio (95% CI) for risk of diabetes was 1.59 (1.34–1.88) for the borderline arterial stiffness group and 2.11 (1.71–2.61) for the elevated arterial stiffness group, compared with the normal ideal arterial stiffness group. In the path analysis, baseline baPWV was associated with follow-up FBG (the standard regression coefficient was 0.09 [95% CI, 0.05–0.10]). In contrast, the standard regression coefficient of baseline FBG for follow-up baPWV (β=0.00 [95% CI, −0.02 to 0.02]) was not significant.

Conclusions:

Arterial stiffness, as measured by baPWV, was associated with risk of developing diabetes. Arterial stiffness appeared to precede the increase in FBG.
Confounding Factors in Renal Denervation Trials
Authors: Kandzari David E. , Mahfoud Felix , Bhatt Deepak L. , Böhm Michael , Weber Michael A. , Townsend Raymond R. , Hettrick Douglas A. , Schmieder Roland E. , Tsioufis Konstantinos , Kario Kazuomi
Published: September 2020

Recent randomized sham-controlled trials have demonstrated significant blood pressure reductions following renal denervation (RDN) in patients with hypertension, both in the presence and absence of antihypertensive therapy. These new data encouraged us to revisit previously published insights into potential clinical trial confounding factors that informed the design and conduct of forthcoming trials. Initially identified confounders related to procedural technique, medication variability, and selected patient subgroups have been addressed in contemporary trial design. Regarding procedural method and technology, blood pressure reductions may be improved by ensuring circumferential lesion creation in the distal renal arteries and branch vessels. Safety of the RDN procedure has been demonstrated in multiple independent meta-analyses including thousands of treated patients with low reported rates of renal vessel complications and maintenance of renal function. However, a newer generation of RDN trials has also introduced insights related to medication adherence, patient selection, and the definition of treatment response. Evolving evidence indicates that RDN therapy may be considered in higher risk populations of uncontrolled hypertension regardless of ethnicity and in patients expressing a strong preference for a nondrug therapy option. Despite advances in procedural technique and clinical trial conduct, inconsistent antihypertensive-drug adherence behavior remains perhaps the most critical clinical trial design issue for device-based hypertension therapies. As the balance in clinical equipoise increasingly favors RDN, justification of sham-controlled trial designs will be revisited, and novel study designs may be required to evaluate the safety and efficacy of novel devices and procedures intended to address the escalating prevalence of poorly controlled hypertension.
Severe Acute Respiratory Syndrome Coronavirus 2, COVID-19, and the Renin-Angiotensin System
Authors: Sparks Matthew A. , South Andrew M. , Badley Andrew D. , Baker-Smith Carissa M. , Batlle Daniel , Bozkurt Biykem , Cattaneo Roberto , Crowley Steven D. , Dell’Italia Louis J. , Ford Andria L. , Griendling Kathy , Gurley Susan B. , Kasner Scott E. , Murray Joseph A. , Nath Karl A. , Pfeffer Marc A. , Rangaswami Janani , Taylor W. Robert , Garovic Vesna D.
Published: September 2020

The coronavirus disease 2019 (COVID-19) pandemic is associated with significant morbidity and mortality throughout the world, predominantly due to lung and cardiovascular injury. The virus responsible for COVID-19—severe acute respiratory syndrome coronavirus 2—gains entry into host cells via ACE2 (angiotensin-converting enzyme 2). ACE2 is a primary enzyme within the key counter-regulatory pathway of the renin-angiotensin system (RAS), which acts to oppose the actions of Ang (angiotensin) II by generating Ang-(1–7) to reduce inflammation and fibrosis and mitigate end organ damage. As COVID-19 spans multiple organ systems linked to the cardiovascular system, it is imperative to understand clearly how severe acute respiratory syndrome coronavirus 2 may affect the multifaceted RAS. In addition, recognition of the role of ACE2 and the RAS in COVID-19 has renewed interest in its role in the pathophysiology of cardiovascular disease in general. We provide researchers with a framework of best practices in basic and clinical research to interrogate the RAS using appropriate methodology, especially those who are relatively new to the field. This is crucial, as there are many limitations inherent in investigating the RAS in experimental models and in humans. We discuss sound methodological approaches to quantifying enzyme content and activity (ACE, ACE2), peptides (Ang II, Ang-[1–7]), and receptors (types 1 and 2 Ang II receptors, Mas receptor). Our goal is to ensure appropriate research methodology for investigations of the RAS in patients with severe acute respiratory syndrome coronavirus 2 and COVID-19 to ensure optimal rigor and reproducibility and appropriate interpretation of results from these investigations.
Association of Albuminuria Levels With the Prescription of Renin-Angiotensin System Blockade
Authors: Qiao Yao , Shin Jung-Im , Chen Teresa K. , Sang Yingying , Coresh Josef , Vassalotti Joseph A. , Chang Alex R. , Grams Morgan E.
Published: September 2020

Multiple clinical guidelines recommend an ACE (angiotensin-converting enzyme) inhibitor or angiotensin II receptor blocker (ARB) in patients with elevated albuminuria, which can be measured through urine albumin-to-creatinine ratio (ACR), protein-to-creatinine ratio, or dipstick. However, how albuminuria test results relate to the prescription of ACE inhibitor/ARB is uncertain. We identified individuals with an ACR measurement between January 1, 2004, and June 30, 2018, and no contraindications or allergy to ACE inhibitor/ARB. We performed multivariable logistic regression analyses to evaluate the association between ACR level and prescription of ACE inhibitor/ARB within 6 months after the test. We applied similar methods to investigate the association of protein-to-creatinine ratio and dipstick measurement results with the prescription of ACE inhibitor/ARB. Among 67 237 individuals with an ACR measurement, 47.7% were already taking an ACE inhibitor or ARB at the time of first ACR measurement. Among the 35 138 individuals who were not on ACE inhibitor/ARB, those with higher ACR levels were more likely to be prescribed ACE inhibitor/ARB in the following 6 months, with steep increases in prescriptions until ACR 300 mg/g, after which the association plateaued. The majority (80.9%) of ACE inhibitor/ARB prescriptions were made by family medicine and internal medicine. A similar pattern held in the cohorts tested by protein-to-creatinine ratio and dipstick measurement. Our study provides evidence that albuminuria test results change patient care, suggesting that adherence to albuminuria testing is a key step in optimal medical management.
SURİYE’DE OYDAŞMACI DEMOKRASİ: OLASI RİSKLER VE FIRSATLAR
Authors: CANYURT Dilek , DALAR Mehmet
Published: September 2020

Siyaset biliminde yapılan yoğun tartışmalardan biri, farklı alt kültürlere sahip ülkelere, hangi demokrasi modellerinin uygun olabileceği konusudur. İçerisinde çok farklı alt kültürleri ve bunlara ait talepleri barındıran Suriye, 2011 yılından beri temelde yönetimsel sorunlarından kaynaklı patlak veren bir iç savaş yaşamaktadır. Ülkenin içinde bulunduğu durum aynı zamanda Suriye için demokrasi tartışmalarının da önünü açmıştır. Bu çalışmada da oydaşmacı demokrasi modeli, Suriye’nin toplumsal, siyasal ve tarihi yapısı üzerinden değerlendirilmiş ve modelin ülke için olası riskleri ve fırsatları ortaya konulmaya çalışılmıştır. Bu çalışmada, ilgili demokrasi teorisi öncelikle ayrıntılı olarak ele alınmış ve Suriye'nin tarihi yapısı incelenmiştir. Daha sonra Suriye'nin siyasal ve toplumsal dokusu analiz edilmiş, bunu genel olarak medya haberlerinin taranması ve ilgili kişisel görüşmelerin kullanılması yoluyla mevcut sürecin araştırılması takip etmiştir. Geleceğin Suriye’si için muhtemel bir model olan ‘consociational’ demokrasi modeli; nispi seçim sisteminin olduğu çok partili sistemde, federal ve ya merkezi olmayan yönetim, güçlü iki meclislilik ve diğer kurumlar ile geniş bir koalisyon kabinesinin temelinde güç paylaşımına vurgu yapan bir sistemi tarif etmektedir. Sonuç olarak modelin ülkedeki ayrılıkların daha bir derinleşmesi ve yeni kurulacak sistemin hantallığından kaynaklı işlevsiz kalması gibi oldukça riskli yönleri de bulunmaktadır. Bununla birlikte oydaşmacı modele ait, toplumun entelektüel kaynaklarını dikkate alarak, oydaşmacı araçları yerleştirmek kaçınılmazdır. Ülkedeki elitlerin etkili oldukları ve uzlaşmaya varabilmek için pazarlıkların yapılması gibi bazı özellikleri, geleceğin Suriye’sinde barış ve istikrarın devamı adına kullanılabileceği düşüncesine varılmıştır.
Courtship behaviour influences social partner choice in male guppies
Authors: Auld Heather L. , Godin Jean-Guy J.
Published: September 2020

Although male courtship displays have evolved primarily to sexually attract females, they also generate inadvertent public information that potentially reveals the courter’s relative sexual attractiveness and the perceived quality and sexual receptivity of the female being courted to nearby eavesdropping male competitors, who in turn may use this information to bias their social partner choices. We tested this hypothesis by first presenting individual eavesdropping male guppies (Poecilia reticulata) the opportunity to simultaneously observe two demonstrator males whose courtship behaviour was manipulated experimentally to differ, following which we tested them for their preference to associate socially with either demonstrator males. Test males preferentially associated with the demonstrator male who they had previously observed courting a female over the other (non-courting) demonstrator. This social association preference was not expressed in the absence of a female to court. Our findings highlight the potential for sexual behaviour influencing male-male social associations in nature.
First description of male and immatures in mite genus Dasythyreus (Acari:
Dasythyreidae)
Authors: KHAUSTOV ALEXANDER A.
Published: September 2020

The male and immatural Dasythyreus polytrichus Khaustov and Abramov, 2010 (Acari: Dasythyreidae), collected from spruce bark in Western Siberia, Russia are described for the first time in the genus. Sexual dimorphism and leg setal development in this species are discussed.
The Micro-situational Context of Sexual Offences Against Adult Women: Unpacking the Role of Guardianship Intensity in Disruption
Authors: Cook Alana , Leclerc Benoit , Reynald Danielle M. , Wortley Richard
Published: September 2020

The current study explores the way guardianship is perceived by offenders and the extent to which it affects the likelihood of disruption in sexual offences against adult females. Specifically, we compare the micro-situational contexts in which sexual offences against adult females are disrupted to those in which these offences are completed. Data on sexual crime events was collected from 138 adult males who were incarcerated for committing a sexual offence against a woman using a self-report questionnaire incorporating a crime-script framework. We found that the presence or availability of a guardian does not guarantee offence disruption. Rather, action taken by the guardian is the critical factor which determines a sexual offender’s decision to cease the offence.
The Junctional Epithelium Is Maintained by a Stem Cell Population
Authors: Yuan X. , Chen J. , Grauer J.A. , Xu Q. , Van Brunt L.A. , Helms J.A.
Published: September 2020

The most fundamental function of an epithelial tissue is to act as a barrier, regulating interactions between the external environment and the body. This barrier function typically requires a contiguous cell layer but since teeth penetrate the oral epithelium, a modified barrier has evolved, called the junctional epithelium (JE). In health, the JE attaches to the tooth, sealing the inside of the body against oral micro-organisms. Breakdown of the JE barrier results in periodontal ligament (PDL) disintegration, alveolar bone resorption, and ultimately tooth loss. Using lineage tracing and DNA pulse-chase analyses, we identified an anatomical location in the JE that supported both fast- and slow-cycling Wnt-responsive stem cells that contributed to self-renewal of the tissue. Stem cells produced daughter cells with an extraordinarily high rate of turnover that maintained JE integrity for 1.4 y in mice. Blocking cell proliferation via a chemotherapeutic agent 5-fluorouracil (5-Fu) eliminated fast-cycling stem cells, which caused JE degeneration, PDL destruction, and bone resorption. Upon removal of 5-Fu, slow-cycling stem cells regenerated both the structure and barrier function of the JE. Taken together, our studies identified a stem cell population in the JE and have potential clinical implications for prevention and treatment of periodontitis.
The Disclosure of Quality on Tourism Performance: Evidence from Top Tourist Cities in China
Authors: Gao Yanyan , Su Wei
Published: September 2020

This article takes advantage of the designation of top tourist cities in China to estimate the impact of quality disclosure on the city tourism economy. According to theories regarding quality disclosure and certification, we develop a tourism promotion hypothesis for the designation, which is then tested with panel data from China’s 284 prefectural-level cities between 2000 and 2015. The difference-in-differences approach shows that gaining the designation increases both domestic and inbound tourism revenues, which is robust to various specifications. Heterogeneity analysis shows that the tourism promotion effect only persists for about three years, decreases over time, is smaller in developed areas, and is less salient for multiple or county-level designations.