bluuebunny/crossref_metadata_2025 huggingface dataset:
Clinical Findings in Diabetes Mellitus Patients with COVID-19
Authors: Guo Ting , Shen Qinxue , Ouyang Xiaoli , Guo Wei , Li Jinhua , He Wenlong , Yu Bo , Wu Chenfang , Zhou Zhiguo , Luo Hong , Peng Hong
Published: January 2021

Backgrounds. Diabetes mellitus (DM) is one of the most common comorbidities in patients with coronavirus disease (COVID-19). We aim to summarize the clinical features of DM patients with COVID-19 and find out potential factors associated with severe disease. Methods. In this retrospective, single-center study, the medical records of patients with COVID-19 in Changsha, Hunan, China, from January 21, 2020, to February 19, 2020, were reviewed. Epidemiological information, clinical features, and outcomes were compared between DM patients admitted to the intensive care unit (ICU) or not. Results. A total of 241 patients confirmed with COVID-19 were enrolled, including 19 DM patients. There were more patients in DM group admitted to the ICU than non-DM group (36.8% vs. 15.8%,

P
=
0.045

). Compared with non-DM group in the ICU, there were more female patients from DM group in the ICU (85.7% vs. 31.4%,

P
=
0.024

). On admission, the mean level of glycated hemoglobin A1c (HbA1c) was higher in the ICU DM patients than that in the non-ICU DM patients (8.5% vs. 7.1%). There were more DM patients with proteinuria in the ICU group than the non-ICU group (57.1% vs. 33.3%). Twelve DM patients (63.2%) changed diabetic therapy during hospitalization, and all DM patients admitted to the ICU used insulin. As of March 14, all 19 DM patients have been discharged, and no death occurred. Conclusions. DM patients with COVID-19 are vulnerable to severe disease, especially for female patients. High levels of HbA1c and proteinuria could be potential risk factors for severe COVID-19 in DM patients. In addition to timely systemic therapy, the control of blood glucose and proper diabetic therapy is essential to improve the prognosis of severe DM patients with COVID-19.
Modern Health Service Utilization and Associated Factors among Adults in Southern Ethiopia
Authors: Bitew Workie Shimelash , Mekonen Niguse , Michael Mulugeta W. , Molla Getahun , Abrha Solomon , Zema Zewde , Tadesse Takele
Published: January 2021

Background. The Ethiopian government is striving to improve the health status of its population through the expansion and strengthening of primary health care services in both rural and urban settings of the country. The study aimed to measure modern health service utilization and associated factors in Wolaita Sodo town, Ethiopia. Method. A cross-sectional study design was implemented from May to June 2019 in Wolaita Sodo town, Ethiopia. All 786 study participants were selected by multistage systematic random sampling. Data were collected by face-to-face interviews using a pretested structured questionnaire. Data were collected by an open data kit. Stata window version 15.0 was also employed for statistical analysis. Multiple logistic regression was conducted, and a 95% confidence interval was considered for interpretation. Result. Health service utilization was 77.2% with (95% CI of 74.1%, 80.0%). In terms of health facilities in which they visit, first 50.6% were at the public health center and 25.5% of them were at Teaching and Referral Hospital. Respondents with marital status married and widowed have higher odds of utilizing health services compared to single marital status (AOR: 2.96; 95% CI: 1.7–5.2 and 9.0; 95% CI: 1.69–48.0), respectively. Respondents with middle and highest wealth status have higher odds of health service utilization than poor wealth status with AOR (1.75 95% CI 1.03–2.97 and 1.58 95% CI; 1.01, 2.77). Similarly, respondents who had chronic disease and perceived poor health status have higher odds of health service utilization. Conclusion. Modern health services utilization was found to be unsatisfactory. Being married, wealth status being middle and high, having chronic health conditions, and having poor perceived health status were found to have a statistically significant association with health service utilization.
Mesenchymal Stem Cells Enhance Therapeutic Effect and Prevent Adverse Gastrointestinal Reaction of Methotrexate Treatment in Collagen-Induced Arthritis
Authors: Zhai Qiming , Dong Jiayi , Zhang Xuesi , He Xiaoning , Fei Dongdong , Jin Yan , Li Bei , Jin Fang
Published: January 2021

Rheumatoid arthritis (RA) is a systemic autoimmune disease characterized by articular destruction and functional loss. Methotrexate (MTX) is effective in RA treatment. However, MTX induces several adverse events and 20%-30% of patients do not respond to MTX. Thus, it is urgent to enhance the therapeutic effects and reduce the side effects of MTX. Recent studies showed that mesenchymal stem cells (MSCs) were participants in anti-inflammation, immunoregulation, and tissue regeneration. However, whether the combined application of MSCs and MTX promotes the therapeutic effects and reduces the side effects of MTX has not been studied. In this study, we used bovine type II collagen to induce rheumatoid arthritis in mice (collagen-induced arthritis, CIA). Then, CIA mice were subjected to MTX or MSC treatment, or both. The therapeutic effect and adverse events of different treatments on RA were evaluated with micro-CT, HE staining, and immunohistochemistry in vivo. Apoptosis and proliferation of MODE-K cells were measured after treated with MTX or/and cocultured with UCs. To test M2 polarization, Raw264.7 macrophages were stimulated by MTX with different concentrations or cocultured with UCs. We found that the combined application of MSCs and MTX increased the therapeutic effects on RA, as evidenced by decreased arthritis score, inflammatory responses, and mortality. Moreover, in this combination remedy, MTX prefers to suppress inflammation by facilitating macrophage polarization to M2 type while UCs prefer to eliminate gastrointestinal side effects of MTX via mitigating the apoptosis of intestinal epithelial cells. Thus, a combination of MTX and UCs is a promising strategy for RA treatment.
[Retracted] Long Noncoding RNAs: New Regulators of Resistance to Systemic Therapies for Gastric Cancer
Authors: Sun Weihong , Jiang Changqing , Ji Ying , Xiao Chao , Song Haiping
Published: January 2021

Gastric cancer (GC) is the second leading cause of cancer mortality and the fourth most commonly diagnosed malignant disease, with approximately 951,000 new cases diagnosed and approximately 723,000 cases of mortality each year. The highest mortality rate of GC is in East Asia, and the lowest is in North America. A large number of studies have demonstrated that GC patients are characterized by higher morbidity, metastasis rates, and mortality and lower early diagnosis rates, radical resection rates, and 5‐year survival rates. All cases of GC can be divided into two important stages, namely, early‐ and advanced‐stage GC, and the stage mainly determines the treatment strategy for and the therapeutic effect in GC patients. Patients with early‐stage GC undergo radical surgery followed by chemotherapy, and the 5‐year survival rate can be as high as 90%. However, patients with advanced‐stage GC cannot undergo radical surgery because they are at risk for metastasis; therefore, they can choose only radiotherapy or chemotherapy and have a poor prognosis. Based on the lack of specific clinical manifestations and detection methods, most GC patients (>70%) are diagnosed in the advanced stage; therefore, continued efforts toward developing treatments have been focused on advanced‐stage GC patients and include molecular targeted therapy, immunotherapy, and small molecular therapy. Nevertheless, in recent years, accumulating evidence has indicated that small molecules, especially long noncoding RNAs (lncRNAs), are involved in the occurrence, development, and progression of GC, and their abundantly dysregulated expression has been identified in GC tissues and cell lines. Therefore, lncRNAs are considered easily detectable molecules and ideal biomarkers or target‐specific agents for the future diagnosis or treatment of GC. In this review, we primarily discuss the status of GC, the role of lncRNAs in GC, and the emerging systemic treatments for GC.
Prevalence and Associated Factors of Visual Hallucinations in Patients with Vascular Cognitive Impairment
Authors: Chen Chih-Lin , Hsu Min-Hsien , Hung Chao-Hsien , Chiu Pai-Yi , Liu Chung-Hsiang
Published: January 2021

Visual hallucinations (VHs) are striking features for dementia, especially dementia with Lewy bodies (DLB). We aimed to study the frequency and associated factors of VH in vascular cognitive impairment (VCI) and investigate the feasibility of clinically diagnosing the mixed pathology of VCI with DLB. This is a multicentre registration study. A consecutive series of VCI patients with and without dementia were enrolled. Frequency of VH and associated factors, including age, gender, education, disease severity, DLB clinical features, vascular risk factors, cognitive function, and neuropsychiatric symptoms, were compared between VCI with VH (VH+) and without VH (VH−). Among the 1281 patients analysed, 155 (12.1%) had VH. The VH+ group was older (

t
=
5.07

;

p
<
0.001

), was more likely to be female (

χ

2

=
13.46

;

p
<
0.001

), and has a higher clinical dementia rating (

χ

2

=
70.51

;

p
<
0.001

). After adjusting for age, gender, and disease severity, the VH+ group had poorer cognition and more severe neuropsychiatric symptoms. The VH+ group was more associated with DLB features in fluctuating cognition (

OR
=
2.48

;

p
<
0.001

), parkinsonism (

OR
=
1.85

;

p
=
0.001

), rapid eye movement (REM) behavioral disorder (

OR
=
4.56

;

p
<
0.001

), and ≧2 DLB core features (

OR
=
26.01

;

p
<
0.001

). VCI patients with VH tend to have more severe dementia, neuropsychiatric symptoms, and poorer cognitive function. Additionally, highly associated with clinical DLB features in VCI with VH raised the possibility of mixed pathology with DLB in this group. More than two core features in VCI might help in diagnosing a mixed pathology with DLB.
Synthesis, Characterization, and Photocatalytic Activity of g-C3N4/GaN-ZnO Composite
Authors: Trang Nguyen Ha , Ha Tran Thi Viet , Viet Nguyen Minh , Phuong Nguyen Minh
Published: January 2021

Recently, photocatalysis process has shown great potential as a low-cost, environmentally friendly, and sustainable method for the water/wastewater treatment. Among that, g-C3N4 is one of the most promising photocatalyst and widely used for a variety of applications. In spite of some unique features such as strong reduction ability, active under visible light, nontoxic, and high stability, g-C3N4 photocatalytic capability under visible light is limited due to fast recombination rate of reactive charges. To deal with this issue, in this study, g-C3N4 is combined with GaN-ZnO for reducing the recombination rate of charge carriers and increasing the active sites. The g-C3N4/GaN-ZnO composite was characterized by several methods such as SEM, EDX, XRD, FT-IR, UV-Vis, and BET. It is also observed that the composite with outstanding features can work effectively under visible light; thus, it is likely to be widely applied in environment treatment, especially in antibiotic residue with more than 90% of tetracycline was decomposed after 3 hours.
Tea Catechin Inhibits Biofilm Formation of Methicillin-Resistant S. aureus
Authors: Zhao Yanying , Qu Yun , Tang Junni , Chen Juan , Liu Ji
Published: January 2021

Staphylococcus aureus (S. aureus) is the most common pathogen causing infections from skin to systemic infections. The success of S. aureus infections can partially be attributed to its antibiotic resistance and to its ability to form biofilm. An increasing prevalence of methicillin-resistant S. aureus (MRSA) becomes a global public health problem in recent decades. Here, the effects of tea catechin extracts on the growth and biofilm formation of three MRSA strains were investigated. The results revealed that tea catechin extracts potently suppressed MRSA growth, and the minimal inhibitory concentration of tea catechin extracts against these MRSA strains was 0.1 g/L. Then, tea catechin extracts inhibited biofilm formation of these strains in a dose-dependent manner measured with a colorimetric method, and the inhibitory effect was also demonstrated by scanning electron microscopy assay. Moreover, adhesin genes biofilm-associated protein (bap), bone sialoprotein-binding protein (bbp), collagen-binding protein (cna), clumping factors A (clfA), fibronectin binding protein A and B (fnbA and fnbB), and intercellular adhesion gene BC (icaBC) were scanned, and the results shown that fnbA and icaBC were present in these three strains. Furthermore, tea catechin extracts depressed fnbA and icaBC expression in the strains. Therefore, inhibition of biofilm formation by tea catechin extracts probably was associated with downregulation of fnbA and icaBC expression in these strains.
Drivers’ Yielding Behavior in Different Pedestrian Crossing Configurations: A Field Survey
Authors: Bella Francesco , Ferrante Chiara
Published: January 2021

Although in recent years road victims have been reported to decrease, the growing number of pedestrians involved in road accidents still remains a social concern. This work analyzes the drivers’ behavior in approach to two different configurations of pedestrian zebra crossing: marked by (1) white stripes over the pavement (named “white zebra crossing”) and (2) white stripes on a red-colored pavement (named “red and white zebra crossing”). Even though the latter configuration is nowadays quite widespread on urban environment, there is no scientific evidence of its actual effectiveness in conditioning drivers’ yielding behavior. This study was aimed at verifying the effectiveness of the red and white zebra crossing on improving road safety at pedestrian crossings. A set of synchronized cameras were used to record drivers’ behavior while approaching the pedestrian crossings. By reconstructing the speed profile of each surveyed driver (309 in total), it was possible to analyze the driver-pedestrian interaction. Data were used to study the driver yielding behavior, to analyze how it is affected by vehicle dynamic constraints, and to identify the significant explanatory variables of a logistic regression model for predicting the drivers’ likelihood of yielding the pedestrian on the different crossing configurations. As a result, significant differences in terms of yielding behavior on the two pedestrian crossing configurations were observed: a higher yielding rate (about 20% higher) and a higher tendency to yield to the pedestrian were reported for the red and white zebra crossing, especially for the most critical conditions of driver-pedestrian interaction. Moreover, the analysis of yielding behavior with respect to vehicle dynamics constraints highlighted that drivers approaching the red and white zebra crossing experienced more opportunities to yield. As a confirmation, logistic regression model showed that the yielding likelihood is significantly and positively affected by the presence of the red and white zebra crossing configuration.
A Comprehensive Analysis Identified Hub Genes and Associated Drugs in Alzheimer’s Disease
Authors: Jing Qi , Zhang Hui , Sun Xiaoru , Xu Yaru , Cao Silu , Fang Yiling , Zhao Xuan , Li Cheng
Published: January 2021

Alzheimer’s disease (AD) is the most common neurodegenerative disease among the elderly and has become a growing global health problem causing great concern. However, the pathogenesis of AD is unclear and no specific therapeutics are available to provide the sustained remission of the disease. In this study, we used comprehensive bioinformatics to determine 158 potential genes, whose expression levels changed between the entorhinal and temporal lobe cortex samples from cognitively normal individuals and patients with AD. Then, we clustered these genes in the protein‐protein interaction analysis and identified six significant genes that had more biological functions. Besides, we conducted a drug‐gene interaction analysis of module genes in the drug‐gene interaction database and obtained 26 existing drugs that might be applied for the prevention and treatment of AD. In addition, a predictive model was built based on the selected genes using different machine learning algorithms to identify individuals with AD. These findings may provide new insights into AD therapy.
Cell-Intrinsic Tumorigenic Functions of PPARγ in Bladder Urothelial Carcinoma
Authors: Sanchez Danielle J. , Missiaen Rindert , Skuli Nicolas , Steger David J. , Simon M. Celeste
Published: January 2021

The role of PPAR gamma (PPARγ) has been well characterized in the developmental process of adipogenesis, yet its aberrant expression patterns and functions in cancer subtypes are less understood. Although PPARγ has been recently demonstrated to play non–cell-autonomous roles in promoting bladder urothelial carcinoma (UC) progression, underlying mechanisms of the cell-intrinsic oncogenic activity remain unknown. Here, we report robust expression and nuclear accumulation of PPARγ in 47% of samples of patients with UC, exceeding mRNA expression patterns published by The Cancer Genome Atlas. In vitro assays revealed for the first time that treatment of UC cells with PPARγ inverse agonist or PPARG knockout by CRISPR-Cas9 reduces proliferation, migration, and invasion of multiple established UC cell lines, most strongly in those characterized by PPARG genomic amplification or activating mutations of RXRA, the obligate heterodimer of PPARγ. Through genome-wide approaches including chromatin immunoprecipitation sequencing and RNA sequencing, we define a novel set of PPARγ-regulated genes in UC, including Sonic Hedgehog (SHH). Similar to PPARγ, genetic inhibition of SHH reduces proliferation and motility. Finally, we demonstrate the PPARγ dependency of UC tumors in vivo by genetic and pharmacologic PPARγ inhibition in subcutaneous xenografts. Collectively, our data indicate that PPARγ promotes UC progression in a subset of patients, at least in part, through cell-autonomous mechanisms linked to SHH signaling.

Implications:

Genome-wide analysis of DNA-binding sites for oncogenic factor PPARγ revealed SHH as a novel downstream target involved in UC progression, providing important insight into the tumorigenic nature and molecular mechanism of PPARγ signaling in UC.
Serine Biosynthesis Is a Metabolic Vulnerability in FLT3-ITD–Driven Acute Myeloid Leukemia
Authors: Bjelosevic Stefan , Gruber Emily , Newbold Andrea , Shembrey Carolyn , Devlin Jennifer R. , Hogg Simon J. , Kats Lev , Todorovski Izabela , Fan Zheng , Abrehart Thomas C. , Pomilio Giovanna , Wei Andrew , Gregory Gareth P. , Vervoort Stephin J. , Brown Kristin K. , Johnstone Ricky W.
Published: January 2021

Internal tandem duplication of the FMS-like tyrosine kinase 3 gene (FLT3-ITD) occurs in 30% of all acute myeloid leukemias (AML). Limited clinical efficacy of FLT3 inhibitors highlights the need for alternative therapeutic modalities in this subset of disease. Using human and murine models of FLT3-ITD–driven AML, we demonstrate that FLT3-ITD promotes serine synthesis and uptake via ATF4-dependent transcriptional regulation of genes in the de novo serine biosynthesis pathway and neutral amino acid transport. Genetic or pharmacologic inhibition of PHGDH, the rate-limiting enzyme of de novo serine biosynthesis, selectively inhibited proliferation of FLT3-ITD AMLs in vitro and in vivo. Moreover, pharmacologic inhibition of PHGDH sensitized FLT3-ITD AMLs to the standard-of-care chemotherapeutic cytarabine. Collectively, these data reveal novel insights into FLT3-ITD–induced metabolic reprogramming and reveal a targetable vulnerability in FLT3-ITD AML.

Significance:

FLT3-ITD mutations are common in AML and are associated with poor prognosis. We show that FLT3-ITD stimulates serine biosynthesis, thereby rendering FLT3-ITD–driven leukemias dependent upon serine for proliferation and survival. This metabolic dependency can be exploited pharmacologically to sensitize FLT3-ITD–driven AMLs to chemotherapy.

This article is highlighted in the In This Issue feature, p. 1307
Targeting the p300/CBP Axis in Lethal Prostate Cancer
Authors: Welti Jonathan , Sharp Adam , Brooks Nigel , Yuan Wei , McNair Christopher , Chand Saswati N. , Pal Abhijit , Figueiredo Ines , Riisnaes Ruth , Gurel Bora , Rekowski Jan , Bogdan Denisa , West William , Young Barbara , Raja Meera , Prosser Amy , Lane Jordan , Thomson Stuart , Worthington Jenny , Onions Stuart , Shannon Jonathan , Paoletta Silvia , Brown Richard , Smyth Don , Harbottle Gareth W. , Gil Veronica S. , Miranda Susana , Crespo Mateus , Ferreira Ana , Pereira Rita , Tunariu Nina , Carreira Suzanne , Neeb Antje J. , Ning Jian , Swain Amanda , Taddei David ,   SU2C/PCF International Prostate Cancer Dream Team, Schiewer Matthew J. , Knudsen Karen E. , Pegg Neil , de Bono Johann S.
Published: January 2021

Resistance to androgen receptor (AR) blockade in castration-resistant prostate cancer (CRPC) is associated with sustained AR signaling, including through alternative splicing of AR (AR-SV). Inhibitors of transcriptional coactivators that regulate AR activity, including the paralog histone acetyltransferase proteins p300 and CBP, are attractive therapeutic targets for lethal prostate cancer. Herein, we validate targeting p300/CBP as a therapeutic strategy for lethal prostate cancer and describe CCS1477, a novel small-molecule inhibitor of the p300/CBP conserved bromodomain. We show that CCS1477 inhibits cell proliferation in prostate cancer cell lines and decreases AR- and C-MYC–regulated gene expression. In AR-SV–driven models, CCS1477 has antitumor activity, regulating AR and C-MYC signaling. Early clinical studies suggest that CCS1477 modulates KLK3 blood levels and regulates CRPC biopsy biomarker expression. Overall, CCS1477 shows promise for the treatment of patients with advanced prostate cancer.

Significance:

Treating CRPC remains challenging due to persistent AR signaling. Inhibiting transcriptional AR coactivators is an attractive therapeutic strategy. CCS1477, an inhibitor of p300/CBP, inhibits growth and AR activity in CRPC models, and can affect metastatic CRPC target expression in serial clinical biopsies.

See related commentary by Rasool et al., p. 1011.

This article is highlighted in the In This Issue feature, p. 995
A Machine Learning Approach Yields a Multiparameter Prognostic Marker in Liver Cancer
Authors: Liu Xiaoli , Lu Jilin , Zhang Guanxiong , Han Junyan , Zhou Wei , Chen Huan , Zhang Henghui , Yang Zhiyun
Published: January 2021

A number of staging systems have been developed to predict clinical outcomes in hepatocellular carcinoma (HCC). However, no general consensus has been reached regarding the optimal model. New approaches such as machine learning (ML) strategies are powerful tools for incorporating risk factors from multiple platforms. We retrospectively reviewed the baseline information, including clinicopathologic characteristics, laboratory parameters, and peripheral immune features reflecting T-cell function, from three HCC cohorts. A gradient-boosting survival (GBS) classifier was trained with prognosis-related variables in the training dataset and validated in two independent cohorts. We constructed a 20-feature GBS model classifier incorporating one clinical feature, 14 laboratory parameters, and five T-cell function parameters obtained from peripheral blood mononuclear cells. The GBS model–derived risk scores demonstrated high concordance indexes (C-indexes): 0.844, 0.827, and 0.806 in the training set and validation sets 1 and 2, respectively. The GBS classifier could separate patients into high-, medium- and low-risk subgroups with respect to death in all datasets (P < 0.05 for all comparisons). A higher risk score was positively correlated with a higher clinical stage and the presence of portal vein tumor thrombus (PVTT). Subgroup analyses with respect to Child–Pugh class, Barcelona Clinic Liver Cancer stage, and PVTT status supported the prognostic relevance of the GBS-derived risk algorithm independent of the conventional tumor staging system. In summary, a multiparameter ML algorithm incorporating clinical characteristics, laboratory parameters, and peripheral immune signatures offers a different approach to identify patients with the greatest risk of HCC-related death.
SEC62 and SEC63 Expression in Hepatocellular Carcinoma and Tumor-Surrounding Liver Tissue
Authors: Casper Markus , Linxweiler Maximilian , Linxweiler Johannes , Zimmermann Richard , Glanemann Matthias , Lammert Frank , Weber Susanne N.
Published: January 2021

Introduction: The endoplasmic reticulum transmembrane proteins Sec61, Sec62, and Sec63 are responsible for the intracellular trafficking of precursor proteins and affect intracellular signaling. SEC62 overexpression has been linked to various human cancers. Our aim was to investigate SEC62 and SEC63 expression in hepatocellular carcinoma (HCC) and surrounding liver tissue. Patients and Methods: Primary liver tissue was collected from 11 consecutive patients (70 ± 9 years; 10 men) who underwent HCC resection. In the HCC and the tumor-surrounding liver tissue we investigated SEC62 und SEC63 mRNA expression using quantitative real-time PCR. For Sec62, immunohistochemistry was performed. Results: SEC62and SEC63 total mRNA contents were significantly (p = 0.001) higher in HCCs (CT 22.5 ± 0.4 and 22.6 ± 0.3) when compared to the surrounding tissue (CT 24.6 ± 0.6 and 25.1 ± 0.9). Using the comparative CTmethod, SEC62 and SEC63 expression in HCC was increased 5- and 8.1-fold, respectively, in comparison to surrounding tissue. For Sec62 immunohistochemistry, the mean immunoreactive scores (IRS) were 7.9 ± 2.9 for HCC and 4.8 ± 1.2 for non-tumorous liver (p = 0.027). The mean IRS in HCC were 5.7 ± 3.5 and 8.9 ± 2.3 for patients without (n = 3) and with tumor recurrence (n = 8), respectively. Conclusions: Overexpression of SEC62 and SEC63 is a common feature of HCC. The role of Sec62 as a prognostic marker for tumor recurrence after surgery and its potential role in treatment stratification must be addressed in future studies.
A evolução da arquitetura comercial no centro de São Paulo à luz das mudanças na legislação urbana
Authors: Sarra Sheila Regina , Mülfarth Roberta Consentino Kronka
Published: January 2021

Neste estudo discute-se o processo evolutivo da arquitetura comercial no centro da cidade de São Paulo, com ênfase no papel desempenhado pelo Estado por meio da legislação e das intervenções urbanísticas. O centro de São Paulo abrigou o primeiro polo de verticalização da cidade, exibindo edifícios comerciais que representam a evolução da arquitetura ao longo de mais de um século. Além de refletir diversos estilos arquitetônicos, as diferentes tipologias dos edifícios comerciais também são fruto das normas e incentivos legais vigentes na época de sua construção.
Palavras chave: Legislação urbana, centro antigo, evolução da arquitetura.
Urbanística, política e sociedade: gestão democrática para as cidades brasileiras
Authors: Silveira Luana Rodrigues Godinho , Costa Staël de Alvarenga Pereira , Teixeira Maria Cristina Villefort
Published: January 2021

O artigo apresenta reflexões teóricas sobre a produção e organização do espaço sob a influência do Estado. O espaço é entendido como o ambiente que sustenta as relações sociais ao mesmo tempo em que é modificado por elas, sendo compreendido como paisagem cultural. Por meio do sistema de regulação urbanística, o Estado intervém na produção e na organização da paisagem. O objetivo do artigo é discutir fundamentos para a construção da gestão democrática dos municípios brasileiros com o intuito de concretizar a noção de direito à cidade. A discussão é feita mediante pesquisa teórica que articula a formação da urbanística moderna, sua vinculação com a ciência moderna e sua ruptura com a política. A (re)vinculação da urbanística com a política, chave para a concretização do direito à cidade, pressupõe estruturas de gestão democrática. Essas estruturas necessitam de aberturas para a democracia direta, essa, exercida por meio da construção e reconstrução de verdades mediante o diálogo, pressupõe um Estado que provê os mínimos sociais para a redução das desigualdades das estruturas de poder e para a superação da distinção entre as atividades de planejamento e gestão.
Plano diretor de drenagem e sua influência no desenvolvimento: loteamento urbano em Fazenda Rio Grande, Paraná
Authors: Ferentz Larissa Maria da Silva , Garcias Carlos Mello , Fonseca Murilo Noli da
Published: January 2021

Os Planos Diretores de Drenagem objetivam a apresentação das áreas de inundação nos municípios, onde, por consequência, não é permitida a expansão imobiliária. O problema está na desatualização desses documentos, pois eles são utilizados como base de análise para tomada de decisões oficiais. A pesquisa tem como objetivo apresentar a influência que o Plano Diretor de Drenagem do Alto Iguaçu pode ocasionar sobre o desenvolvimento urbano. Com a realização de um estudo de caso na cidade de Fazenda Rio Grande foi possível confirmar que o Plano influencia não apenas na promoção de loteamentos, mas também no dia-a-dia das pessoas, com a ocupação da área para atividades ilícitas, despejo de resíduos e insegurança local. Tais problemas podem ser solucionados a partir do envolvimento do governo e da sociedade, buscando o equilíbrio entre as melhores condições do ambiente e o aumento da qualidade de vida da população local
Contribuições dos parâmetros urbanísticos para o urbanismo bioclimático
Authors: Melo Artur Paulo Schimbergui Sandes de , Freitas Ruskin Fernandes Marinho de
Published: January 2021

O atual processo de urbanização tem alterado o ambiente, negativamente. Os parâmetros urbanísticos podem contribuir para a redução dos impactos ambientais, promovendo a qualidade de vida e o conforto ambiental. Para se alcançar o conforto em clima tropical litorâneo quente e úmido, as principais estratégias são ventilação, sombreamento e proteção contra as chuvas. O objetivo deste artigo é analisar as contribuições da legislação urbana, em especial, do Plano Diretor Municipal, Lei Nº 16.176/1996, que dispõe sobre a produção e organização do espaço urbano, em Recife - PE, que promovam o solo natural, a vegetação e a permeabilidade aos ventos e, por conseguinte, o bioclimatismo, a sustentabilidade e o conforto ambiental.
Interactions Between Enhanced Polygenic Risk Scores and Lifestyle for Cardiovascular Disease, Diabetes, and Lipid Levels
Authors: Ye Yixuan , Chen Xi , Han James , Jiang Wei , Natarajan Pradeep , Zhao Hongyu
Published: January 2021

Background:

Both lifestyle and genetic factors confer risk for cardiovascular diseases, type 2 diabetes, and dyslipidemia. However, the interactions between these 2 groups of risk factors were not comprehensively understood due to previous poor estimation of genetic risk. Here we set out to develop enhanced polygenic risk scores (PRS) and systematically investigate multiplicative and additive interactions between PRS and lifestyle for coronary artery disease, atrial fibrillation, type 2 diabetes, total cholesterol, triglyceride, and LDL-cholesterol.

Methods:

Our study included 276 096 unrelated White British participants from the UK Biobank. We investigated several PRS methods (P+T, LDpred, PRS continuous shrinkage, and AnnoPred) and showed that AnnoPred achieved consistently improved prediction accuracy for all 6 diseases/traits. With enhanced PRS and combined lifestyle status categorized by smoking, body mass index, physical activity, and diet, we investigated both multiplicative and additive interactions between PRS and lifestyle using regression models.

Results:

We observed that healthy lifestyle reduced disease incidence by similar multiplicative magnitude across different PRS groups. The absolute risk reduction from lifestyle adherence was, however, significantly greater in individuals with higher PRS. Specifically, for type 2 diabetes, the absolute risk reduction from lifestyle adherence was 12.4% (95% CI, 10.0%–14.9%) in the top 1% PRS versus 2.8% (95% CI, 2.3%–3.3%) in the bottom PRS decile, leading to a ratio of >4.4. We also observed a significant interaction effect between PRS and lifestyle on triglyceride level.

Conclusions:

By leveraging functional annotations, AnnoPred outperforms state-of-the-art methods on quantifying genetic risk through PRS. Our analyses based on enhanced PRS suggest that individuals with high genetic risk may derive similar relative but greater absolute benefit from lifestyle adherence.
Perceived Versus Actual Risks of 30-Day Readmission in Patients With Cardiovascular Disease
Authors: Xu Hanzhang , Farmer Heather R. , Granger Bradi B. , Thomas Kevin L. , Peterson Eric D. , Dupre Matthew E.
Published: January 2021

Background:

Cardiovascular disease (CVD) is the leading cause of hospitalization in the United States, and patients with CVD are at a high risk of readmission after discharge. We examined whether patients’ perceived risk of readmission at discharge was associated with actual 30-day readmissions in patients hospitalized with CVD.

Methods:

We recruited 730 patients from the Duke Heart Center who were admitted for treatment of CVD between January 1, 2015, and August 31, 2017. A standardized survey was linked with electronic health records to ascertain patients’ perceived risk of readmission, and other sociodemographic, psychosocial, behavioral, and clinical data before discharge. All-cause readmission within 30 days after discharge was examined.

Results:

Nearly 1-in-3 patients perceived a high risk of readmission at index admission and those who perceived a high risk had significantly more readmissions within 30 days than patients who perceived low risks of readmission (23.6% versus 15.8%,
P
=0.016). Among those who perceived a high risk of readmission, non-White patients (odds ratio [OR], 2.07 [95% CI, 1.28–3.36]), those with poor self-rated health (OR, 2.30 [95% CI, 1.38–3.85]), difficulty accessing care (OR, 2.72 [95% CI, 1.24–6.00]), and prior hospitalizations in the past year (OR, 2.13 [95% CI, 1.21–3.74]) were more likely to be readmitted. Among those who perceived a low risk of readmission, patients who were widowed (OR, 2.69 [95% CI, 1.60–4.51]) and reported difficulty accessing care (OR, 1.89 [95% CI, 1.07–3.33]) were more likely to be readmitted.

Conclusions:

Patients who perceived a high risk of readmission had a higher rate of 30-day readmission than patients who perceived a low risk. These findings have important implications for identifying CVD patients at a high risk of 30-day readmission and targeting the factors associated with perceived and actual risks of readmission.
The Cardiovascular Quality Improvement and Care Innovation Consortium
Authors:   CV-QUIC Collaborators, Bradley Steven M. , Adusumalli Srinath , Amin Amit P. , Borden William B. , Das Sandeep R. , Downey William E. , Ebinger Joseph E. , Gelbman Joy , Gluckman Ty J. , Goyal Abhinav , Gupta Divya , Khot Umesh N. , Levy Andrew E. , Mutharasan R. Kannan , Rush Pam , Strauss Craig E. , Shreenivas Satya , Ho P. Michael
Published: January 2021

Despite decades of improvement in the quality and outcomes of cardiovascular care, significant gaps remain. Existing quality improvement strategies are often limited in scope to specific clinical conditions and episodic care. Health services and outcomes research is essential to inform gaps in care but rarely results in the development and implementation of care delivery solutions. Although individual health systems are engaged in projects to improve the quality of care delivery, these efforts often lack a robust study design or implementation evaluation that can inform generalizability and further dissemination. Aligning the work of health care systems and health services and outcomes researchers could serve as a strategy to overcome persisting gaps in cardiovascular quality and outcomes. We describe the inception of the Cardiovascular Quality Improvement and Care Innovation Consortium that seeks to rapidly improve cardiovascular care by (1) developing, implementing, and evaluating multicenter quality improvement projects using innovative care designs; (2) serving as a resource for quality improvement and care innovation partners; and (3) establishing a presence within existing quality improvement and care innovation structures. Success of the collaborative will be defined by projects that result in changes to care delivery with demonstrable impacts on the quality and outcomes of care across multiple health systems. Furthermore, insights gained from implementation of these projects across sites in Cardiovascular Quality Improvement and Care Innovation Consortium will inform and promote broad dissemination for greater impact.
Gaps in Evidence‐Based Therapy Use in Insured Patients in the United States With Type 2 Diabetes Mellitus and Atherosclerotic Cardiovascular Disease
Authors: Nelson Adam J. , Ardissino Maddalena , Haynes Kevin , Shambhu Sonali , Eapen Zubin J. , McGuire Darren K. , Carnicelli Anthony , Lopes Renato D. , Green Jennifer B. , O’Brien Emily C. , Pagidipati Neha J. , Granger Christopher B.
Published: January 2021

Background

Evidence‐based therapies are generally underused for cardiovascular risk reduction; however, less is known about contemporary patients with type 2 diabetes mellitus and atherosclerotic cardiovascular disease.

Methods and Results

Pharmacy and medical claims data from within Anthem were queried for patients with established atherosclerotic cardiovascular disease and type 2 diabetes mellitus. Using an index date of April 18, 2018, we evaluated the proportion of patients with a prescription claim for any of the 3 evidence‐based therapies on, or covering, the index date ±30 days: high‐intensity statin, angiotensin‐converting enzyme inhibitor or angiotensin receptor blocker, and sodium glucose cotransporter‐2 inhibitor or glucagon‐like peptide‐1 receptor agonist. The potential benefit of achieving 100% adoption of all 3 evidence‐based therapies was simulated using pooled treatment estimates from clinical trials. Of the 155 958 patients in the sample, 24.7% were using a high‐intensity statin, 53.1% were using an angiotensin‐converting enzyme inhibitor or angiotensin receptor blocker, and 9.9% were using either an sodium glucose cotransporter‐2 inhibitor or glucagon‐like peptide‐1 receptor agonists. Overall, only 2.7% of the population were covered by prescriptions for all 3 evidence‐based therapies, and 37.4% were on none of them. Over a 12‐month period, 70.6% of patients saw a cardiologist, while only 18% saw an endocrinologist. Increasing the use of evidence‐based therapies to 100% over 3 years of treatment could be expected to reduce 4546 major atherosclerotic cardiovascular events (myocardial infarction, stroke, or cardiovascular death) in eligible but untreated patients.

Conclusions

Alarming gaps exist in the contemporary use of evidence‐based therapies in this large population of insured patients with type 2 diabetes mellitus and atherosclerotic cardiovascular disease. These data provide a call to action for patients, providers, industry, regulators, professional societies, and payers to close these gaps in care.
Genetic Etiology of Left‐Sided Obstructive Heart Lesions: A Story in Development
Authors: Parker Lauren E. , Landstrom Andrew P.
Published: January 2021

Congenital heart disease is the most common congenital defect observed in newborns. Within the spectrum of congenital heart disease are left‐sided obstructive lesions (LSOLs), which include hypoplastic left heart syndrome, aortic stenosis, bicuspid aortic valve, coarctation of the aorta, and interrupted aortic arch. These defects can arise in isolation or as a component of a defined syndrome; however, nonsyndromic defects are often observed in multiple family members and associated with high sibling recurrence risk. This clear evidence for a heritable basis has driven a lengthy search for disease‐causing variants that has uncovered both rare and common variants in genes that, when perturbed in cardiac development, can result in LSOLs. Despite advancements in genetic sequencing platforms and broadening use of exome sequencing, the currently accepted LSOL‐associated genes explain only 10% to 20% of patients. Further, the combinatorial effects of common and rare variants as a cause of LSOLs are emerging. In this review, we highlight the genes and variants associated with the different LSOLs and discuss the strengths and weaknesses of the present genetic associations. Furthermore, we discuss the research avenues needed to bridge the gaps in our current understanding of the genetic basis of nonsyndromic congenital heart disease.
Thrombocytopenia and Clinical Outcomes in Intracerebral Hemorrhage
Authors: Mrochen Anne , Sprügel Maximilian I. , Gerner Stefan T. , Sembill Jochen A. , Lang Stefan , Lücking Hannes , Kuramatsu Joji B. , Huttner Hagen B.
Published: January 2021

Background and Purpose:

The impact of platelets on hematoma enlargement (HE) of intracerebral hemorrhage (ICH) is not yet sufficiently elucidated. Especially the role of reduced platelet counts on HE and clinical outcomes is still poorly understood. This study investigated the influence of thrombocytopenia on HE, functional outcome, and mortality in patients with ICH with or without prior antiplatelet therapy (APT).

Methods:

Individual participant data of multicenter cohort studies (multicenter RETRACE program [German-Wide Multicenter Analysis of Oral Anticoagulation-Associated Intracerebral Hemorrhage] and single-center UKER-ICH registry [Universitätsklinikum Erlangen Cohort of Patients With Spontaneous ICH]) were grouped into APT and non-APT ICH patients according to the platelet count, that is, with or without thrombocytopenia (cells <150×10
9
/L). Of all patients, 51.5% (1124 of 2183) were on vitamin K antagonist. Imbalances in baseline characteristics including proportions of vitamin K antagonist patients were addressed using propensity score matching. Outcome analyses included HE (>33%), as well as mortality and functional outcome, after 3 months using the modified Rankin Scale, dichotomized into favorable (modified Rankin Scale score, 0–3) and unfavorable (modified Rankin Scale score, 4–6).

Results:

Of overall 2252 ICH patients, 11.4% (52 of 458) under APT and 14.0% (242 of 1725) without APT presented with thrombocytopenia on admission. The proportion of patients with HE was not significantly different between patients with or without thrombocytopenia among APT and non-APT ICH patients after propensity score matching (HE: APT patients: 9 of 40 [22.5%] thrombocytopenia versus 27 of 115 [23.5%] nonthrombocytopenia,
P
=0.89; non-APT patients: 54 of 174 [31.0%] thrombocytopenia versus 106 of 356 [29.8%] nonthrombocytopenia,
P
=0.77). In both (APT and non-APT) propensity score matching cohorts, there were no significant differences regarding functional outcome. Mortality after 3 months did not differ among non-APT patients, whereas the mortality rate was significantly higher for APT patients with thrombocytopenia versus APT patients with normal platelet count (APT: 29 of 46 [63.0%] thrombocytopenia versus 58 of 140 [41.4%] nonthrombocytopenia,
P
=0.01; non-APT: 95 of 227 [41.9%] thrombocytopenia versus 178 of 455 [39.1%] nonthrombocytopenia,
P
=0.49).

Conclusions:

Our study implies that thrombocytopenia does not affect rates of HE and functional outcome among ICH patients, neither in patients with nor without APT. In light of increased mortality, the significance of platelet transfusions for ICH patients with thrombocytopenia and previous APT should be explored in future studies.
Age-dependent walking and feeding of the assassin bug Amphibolus venator
Authors: Matsumura Kentarou , Iwaya Mana , Nagaya Naohisa , Fujisawa Ryusuke , Miyatake Takahisa
Published: January 2021

Animal behaviours often dependent on age. In many insect species, walking shows an age-dependent decline, and food intake may also be dependent on age. However, few studies have investigated the relationship between age and walking or food intake. In the present study, we compared walking traits and food intake among individuals of different ages in the assassin bug Amphibolus venator (Hemiptera, Reduviidae). The present results showed an age-dependent decline in walking, similar to findings in many animal species. On the other hand, food intake showed a positive correlation with age. Therefore, the decline in walking did not lead to a decline in feeding. The positive relationship between food intake and age may be related to the type of predation, sit-and-wait, used by A. venator via alterations in investment in reproductive traits with age.
Catalogue of the Anthribidae (Coleoptera: Curculionoidea) of Panama, including new country records and a key to genera
Authors: ORELLANA K. SAMANTA , BARRIOS HÉCTOR
Published: January 2021

An updated catalogue of the Anthribidae of Panama is provided, including 134 species in 30 genera, 14 tribes and two subfamilies. A total of 44 species in the following genera are recorded for the first time in the country: Corrhecerus Schoenherr, Eugonus Schoenherr, Euparius Schoenherr, Gymnognathus Schoenherr, Nemotrichus Labram & Imhoff, Phaenithon Schoenherr, Piesocorynus Dejean, Anthiera Alonso-Zarazaga & Lyal, Ptychoderes Schoenherr, Stenocerus Schoenherr and Toxonotus Lacordaire. The genera Corrhecerus Schoenherr, Eugonus Schoenherr and Anthiera Alonso-Zarazaga & Lyal are recorded for the first time in Panama. Although more than 60 unnamed morphospecies were recognized in Panamanian and American collections, at this time no new taxa are described. An illustrated key to the genera of Anthribidae of Panama is included.
Quantifying the Uncertainty of the Future Hydrological Impacts of Climate Change: Comparative Analysis of an Advanced Hierarchical Sensitivity in Humid and Semiarid Basins
Authors: Ju Jiali , Dai Heng , Wu Chuanhao , Hu Bill X. , Ye Ming , Chen Xingyuan , Gui Dongwei , Liu Haifan , Zhang Jin
Published: January 2021

Comparison and quantification of different uncertainties of future climate change involved in the modeling of a hydrological system are highly important for both hydrological modelers and policy-makers. However, few studies have accurately estimated the relative importance of different sources of uncertainty at different spatiotemporal scales. Here, a hierarchical sensitivity analysis framework (HSAF) incorporated with a variance-based global sensitivity analysis is developed to quantify the spatiotemporal contributions of different uncertainties in hydrological impacts of climate change in two different climatic (humid and semiarid) basins in China. The uncertainty sources include three emission scenarios (ESs), 20 global climate models (GCs), three hydrological models (HMs), and the associated sensitive hydrological parameters (PAs) screened and sampled by the Morris and Latin hypercube sampling methods, respectively. The results indicate that the overall trend of uncertainty is PA > HM > GC > ES, but their uncertainties have discrepancies in projections of different hydrological variables. The HM uncertainty in annual and monthly discharge projections is generally larger than the PA uncertainty in the humid basin than semiarid basin. The PA has greater uncertainty in extreme hydrological event (annual peak discharge) projections than in annual discharge projections for both basins (particularly for the humid basin), but contributes larger uncertainty to annual and monthly discharge projections in the semiarid basin than humid basin. The GC contributes larger uncertainty in all the hydrological variables projections in the humid basin than semiarid basin, while the ES uncertainty is rather limited in both basins. Overall, our results suggest there is greater spatiotemporal variability of hydrological uncertainty in more arid regions.