bluuebunny/crossref_metadata_2025 huggingface dataset:
Characterizing Hotspots and Frontier Landscapes of Diabetes‐Specific Distress from 2000 to 2018: A Bibliometric Study
Authors: Li Dan , Dai Fu-Min , Xu Juan-Juan , Jiang Meng-Die
Published: January 2020

Objectives. This work aims to comprehensively characterize hotspots and frontier landscapes concerning diabetes‐specific distress from 2000 to 2018. Materials and Methods. Firstly, diabetes‐specific distress‐related literature was retrieved and downloaded from the Web of Science Core Collection (WoSCC). Secondly, WoSCC self‐contained toolkits and GraphPad Prism7 were conducted to analyze general characteristics, including literature products, countries, institutes, authors, and journal resource. Finally, CiteSpace V Toolkits was put forward to implement advanced analysis, consisting of keyword‐term frequency and co‐occurrence, references‐cited frequency and co‐occurrence, and burst detection for keyword terms and references cited, which uncovers the hotspots and frontiers of diabetes‐specific distress. Results. After preprocessing, our study included a total of 1051 papers concerning diabetes‐specific distress. Publication outputs increased smoothly year by year. Compared with other journals, diabetic medicine delivered the largest number of documents. The United States occupied the leading positions, and the most productive institution was the University of California System in terms of literature products. Fisher L. has the highest references‐cited frequency. Prevalence of diabetes‐specific distress, diabetes‐specific distress and glycemic control, diabetes‐specific distress and depression comorbidity, and diabetes‐specific distress and risk factors were the research hotspots, whereas the measure of diabetes‐specific distress and latent and serious/severe diabetes‐specific distress was the research frontiers. Conclusions. Overall, our study may inspire researchers to show great interest in diabetes‐specific distress in the next few years.
BAHK: Flexible Automated Binary Analysis Method with the Assistance of Hardware and System Kernel
Authors: Pan Jiaye , Zhuang Yi , Sun Binglin
Published: January 2020

To protect core functions, applications often utilize the countermeasure techniques such as antidebugging to avoid analysis by outsiders, especially the malware. Dynamic binary instrumentation is commonly used in the analysis of binary programs. However, it can be easily detected and has stability and applicability problems as it involves program rewriting and just-in-time compilation. This paper proposes a new lightweight analysis method for binary programs with the assistance of hardware features and the operating system kernel, named BAHK, which can automatically analyze the target program by stealth and has wide applicability. With the support of underlying infrastructures, this paper designs several optimization strategies and specific analysis approaches at instruction level to reduce the impact of fine-grained analysis on the performance of target program so that it can be well applied in practice. The experimental results show that the proposed method has good stealthiness, low memory consumption, and positive user experience. In some cases, it shows better analysis performance than the traditional dynamic binary instrumentation method. Finally, the real case studies further show its feasibility and effectiveness.
Activation of Canonical BMP4-SMAD7 Signaling Suppresses Breast Cancer Metastasis
Authors: Eckhardt Bedrich L. , Cao Yuan , Redfern Andrew D. , Chi Lap Hing , Burrows Allan D. , Roslan Suraya , Sloan Erica K. , Parker Belinda S. , Loi Sherene , Ueno Naoto T. , Lau Peter K. H. , Latham Bruce , Anderson Robin L.
Published: January 2020

Metastasis is the major cause of death in patients with cancer; with no therapeutic cure, treatments remain largely palliative. As such, new targets and therapeutic strategies are urgently required. Here, we show that bone morphogenetic protein-4 (BMP4) blocks metastasis in animal models of breast cancer and predicts improved survival in patients. In preclinical models of spontaneous metastasis, BMP4 acted as an autocrine mediator to modulate a range of known metastasis-regulating genes, including Smad7, via activation of canonical BMP-SMAD signaling. Restored BMP4 expression or therapeutically administered BMP4 protein, blocked metastasis and increased survival by sensitizing cancer cells to anoikis, thereby reducing the number of circulating tumor cells. Gene silencing of Bmp4 or its downstream mediator Smad7, reversed this phenotype. Administration of recombinant BMP4 markedly reduced spontaneous metastasis to lung and bone. Elevated levels of BMP4 and SMAD7 were prognostic for improved recurrence-free survival and overall survival in patients with breast cancer, indicating the importance of canonical BMP4 signaling in the suppression of metastasis and highlighting new avenues for therapy against metastatic disease.

Significance:

Targeting the BMP4–SMAD7 signaling axis presents a novel therapeutic strategy to combat metastatic breast cancer, a disease that has had no reduction in patient mortality over 20 years.
An ABC Transporter Drives Medulloblastoma Pathogenesis by Regulating Sonic Hedgehog Signaling
Authors: Wijaya Juwina , Vo BaoHan T. , Liu Jingjing , Xu Beisi , Wu Gang , Wang Yao , Peng Junmin , Zhang Jin , Janke Laura J. , Orr Brent A. , Yu Jiyang , Roussel Martine F. , Schuetz John D.
Published: January 2020

Mutations in Sonic hedgehog (SHH) signaling promote aberrant proliferation and tumor growth. SHH-medulloblastoma (MB) is among the most frequent brain tumors in children less than 3 years of age. Although key components of the SHH pathway are well-known, we hypothesized that new disease-modifying targets of SHH-MB might be identified from large-scale bioinformatics and systems biology analyses. Using a data-driven systems biology approach, we built a MB-specific interactome. The ATP-binding cassette transporter ABCC4 was identified as a modulator of SHH-MB. Accordingly, increased ABCC4 expression correlated with poor overall survival in patients with SHH-MB. Knockdown of ABCC4 expression markedly blunted the constitutive activation of the SHH pathway secondary to Ptch1 or Sufu insufficiency. In human tumor cell lines, ABCC4 knockdown and inhibition reduced full-length GLI3 levels. In a clinically relevant murine SHH-MB model, targeted ablation of Abcc4 in primary tumors significantly reduced tumor burden and extended the lifespan of tumor-bearing mice. These studies reveal ABCC4 as a potent SHH pathway regulator and a new candidate to target with the potential to improve SHH-MB therapy.

Significance:

These findings identify ABCC4 transporter as a new target in SHH-MB, prompting the development of inhibitors or the repurporsing of existing drugs to target ABCC4.
A Feedback Circuitry between Polycomb Signaling and Fructose-1, 6-Bisphosphatase Enables Hepatic and Renal Tumorigenesis
Authors: Liao Kun , Deng Shuye , Xu Liyan , Pan Wenfeng , Yang Shiyu , Zheng Fufu , Wu Xingui , Hu Hongrong , Liu Zhijun , Luo Junhang , Zhang Rui , Kuang Dong-Ming , Dong Jiajun , Wu Yi , Zhang Hui , Zhou Penghui , Bei Jin-Xin , Xu Yang , Ji Yin , Wang Peng , Ju Huai-Qiang , Xu Rui-Hua , Li Bo
Published: January 2020

Suppression of gluconeogenesis elevates glycolysis and is commonly observed in tumors derived from gluconeogenic tissues including liver and kidney, yet the definitive regulatory mechanism remains elusive. Here, we screened an array of transcription regulators and identified the enhancer of zeste homolog 2 (EZH2) as a key factor that inhibits gluconeogenesis in cancer cells. Specifically, EZH2 repressed the expression of a rate-limiting gluconeogenic enzyme fructose-1, 6-bisphosphatase 1 (FBP1) and promoted tumor growth primarily through FBP1 suppression. Furthermore, EZH2 was upregulated by genotoxins that commonly induce hepatic and renal tumorigenesis. Genotoxin treatments augmented EZH2 acetylation, leading to reduced association between EZH2 and its E3 ubiquitin ligase SMURF2. Consequently, EZH2 became less ubiquitinated and more stabilized, promoting FBP1 attenuation and tumor formation. Intriguingly, FBP1 physically interacted with EZH2, competed for EZH2 binding, and dissembled the polycomb complex. Therefore, FBP1 suppresses polycomb-initiated transcriptional responses and constitutes a double-negative feedback loop indispensable for EZH2-promoted tumorigenesis. Finally, EZH2 and FBP1 levels were inversely correlated in tumor tissues and accurately predicted patient survival. This work reveals an unexpected cross-talk between epigenetic and metabolic events, and identifies a new feedback circuitry that highlights EZH2 inhibitors as liver and kidney cancer therapeutics.

Significance:

A novel feedback loop involving EZH2 and suppression of the gluconeogenesis enzyme FBP1 promotes hepatocellular cancer growth.

See related commentary by Leithner, p. 657
SLC43A3 Is a Biomarker of Sensitivity to the Telomeric DNA Damage Mediator 6-Thio-2′-Deoxyguanosine
Authors: Mender Ilgen , Batten Kimberly , Peyton Michael , Vemula Aishwarya , Cornelius Crystal , Girard Luc , Gao Boning , Minna John D. , Shay Jerry W.
Published: January 2020

Cell membrane transporters facilitate the passage of nucleobases and nucleosides for nucleotide synthesis and metabolism, and are important for the delivery of nucleoside analogues used in anticancer drug therapy. Here, we investigated if cell membrane transporters are involved in the cellular uptake of the nucleoside analogue DNA damage mediator 6-thio-2′-deoxyguanosine (6-thio-dG). A large panel of non–small cell lung cancer (NSCLC) cell lines (73 of 77) were sensitive to 6-thio-dG; only four NSCLC lines were resistant to 6-thio-dG. When analyzed by microarray and RNA sequencing, the resistant NSCLC cell lines clustered together, providing a molecular signature for patients that may not respond to 6-thio-dG. Significant downregulation of solute carrier family 43 A3 (SLC43A3), an equilibrative nucleobase transporter, was identified as a candidate in this molecular resistance signature. High levels of SLC43A3 mRNA predicted sensitivity to 6-thio-dG and therefore SLC43A3 could serve as a promising biomarker for 6-thio-dG sensitivity in patients with NSCLC.

Significance:

These findings identify a biomarker of resistance to the telomeric DNA damage mediator 6-thio-2′-deoxyguanosine.
Towards Multidrug Adaptive Therapy
Authors: West Jeffrey , You Li , Zhang Jingsong , Gatenby Robert A. , Brown Joel S. , Newton Paul K. , Anderson Alexander R.A.
Published: January 2020

A new ecologically inspired paradigm in cancer treatment known as “adaptive therapy” capitalizes on competitive interactions between drug-sensitive and drug-resistant subclones. The goal of adaptive therapy is to maintain a controllable stable tumor burden by allowing a significant population of treatment-sensitive cells to survive. These, in turn, suppress proliferation of the less-fit resistant populations. However, there remain several open challenges in designing adaptive therapies, particularly in extending these therapeutic concepts to multiple treatments. We present a cancer treatment case study (metastatic castrate-resistant prostate cancer) as a point of departure to illustrate three novel concepts to aid the design of multidrug adaptive therapies. First, frequency-dependent “cycles” of tumor evolution can trap tumor evolution in a periodic, controllable loop. Second, the availability and selection of treatments may limit the evolutionary “absorbing region” reachable by the tumor. Third, the velocity of evolution significantly influences the optimal timing of drug sequences. These three conceptual advances provide a path forward for multidrug adaptive therapy.

Significance:

Driving tumor evolution into periodic, repeatable treatment cycles provides a path forward for multidrug adaptive therapy.
Targeting PD-1 or PD-L1 in Metastatic Kidney Cancer: Combination Therapy in the First-Line Setting
Authors: Aggen David H. , Drake Charles G. , Rini Brian I.
Published: January 2020

Recent FDA approvals of regimens targeting programmed death 1 (PD-1) in combination with anti-CTLA-4 or with VEGF tyrosine kinase inhibitors are reshaping front-line therapy for metastatic kidney cancer. In parallel, therapeutics specific for programmed death ligand 1 (PD-L1), one of the two major ligands for PD-1, are under continued investigation. Surprisingly, not all PD-1 and PD-L1 agents lead to similar clinical outcomes, potentially due to biological differences in the cellular expression and regulation of these targets. Here, we review current clinical data on combination immune checkpoint inhibitor therapy in metastatic kidney cancer and discuss the relevant biology of PD-1 and PD-L1. The design of future rational combination therapy trials in metastatic renal cell carcinoma will rely upon an understanding of this biology, along with an evolving understanding of immune cell populations and their functional states in the tumor microenvironment.
Combined Src/EGFR Inhibition Targets STAT3 Signaling and Induces Stromal Remodeling to Improve Survival in Pancreatic Cancer
Authors: Dosch Austin R. , Dai Xizi , Reyzer Michelle L. , Mehra Siddharth , Srinivasan Supriya , Willobee Brent A. , Kwon Deukwoo , Kashikar Nilesh , Caprioli Richard , Merchant Nipun B. , Nagathihalli Nagaraj S.
Published: January 2020

Lack of durable response to cytotoxic chemotherapy is a major contributor to the dismal outcomes seen in pancreatic ductal adenocarcinoma (PDAC). Extensive tumor desmoplasia and poor vascular supply are two predominant characteristics which hinder the delivery of chemotherapeutic drugs into PDAC tumors and mediate resistance to therapy. Previously, we have shown that STAT3 is a key biomarker of therapeutic resistance to gemcitabine treatment in PDAC, which can be overcome by combined inhibition of the Src and EGFR pathways. Although it is well-established that concurrent EGFR and Src inhibition exert these antineoplastic properties through direct inhibition of mitogenic pathways in tumor cells, the influence of this combined therapy on stromal constituents in PDAC tumors remains unknown. In this study, we demonstrate in both orthotopic tumor xenograft and Ptf1acre/+;LSL-KrasG12D/+;Tgfbr2flox/flox (PKT) mouse models that concurrent EGFR and Src inhibition abrogates STAT3 activation, increases microvessel density, and prevents tissue fibrosis in vivo. Furthermore, the stromal changes induced by parallel EGFR and Src pathway inhibition resulted in improved overall survival in PKT mice when combined with gemcitabine. As a phase I clinical trial utilizing concurrent EGFR and Src inhibition with gemcitabine has recently concluded, these data provide timely translational insight into the novel mechanism of action of this regimen and expand our understanding into the phenomenon of stromal-mediated therapeutic resistance.

Implications:

These findings demonstrate that Src/EGFR inhibition targets STAT3, remodels the tumor stroma, and results in enhanced delivery of gemcitabine to improve overall survival in a mouse model of PDAC.
Individualized Homeopathic Treatment in Women with Recurrent Cystitis: A Retrospective Case Series
Authors: Gaertner Katharina , von Ammon Klaus , Frei-Erb Martin
Published: January 2020

Background: Recurrent urinary tract infections are of importance for public health as most clinicians are faced with repeated and long-term administration of broad-spectrum antimicrobial agents leading to an increased risk of resistant bacteria. One encouraging treatment approach may be individualized homeopathy. Case Reports: Here, four female cases with recurrent urinary tract infections are reported. They were treated successfully with the homeopathic strategy after several conventional approaches revealed no improvement. The follow-up period was a minimum of 3 years and the frequency of episodes with urinary tract infection as well as of antibiotic treatment was documented. Additionally, the patients were asked to assess the treatment outcome retrospectively in a validated questionnaire. Results: The treatment resulted in a reduction of urinary tract infections and the need for antibiotics from monthly to less than 3 times a year. Three of the four women had no cystitis and related intake of antibiotics for more than 1.5 years. A relapse of symptoms could be treated efficiently with a repetition of the homeopathic remedy. All subjective outcome assessments resulted positive. Conclusion: This case series suggests a possible benefit of individualized homeopathic treatment for female patients with recurrent urinary tract infections. Larger observational studies and controlled investigations are warranted.
A Study of Morphological Changes in Renal Afferent Arterioles Induced by Angiotensin II Type 1 Receptor Blockers in Hypertensive Patients
Authors: Nagai Yohko , Yamabe Fumito , Sasaki Yosuke , Ishii Takamasa , Nakanishi Kazushige , Nakajima Koichi , Shibuya Kazutoshi , Mikami Tetsuo , Akasaka Yoshikiyo , Urita Yoshihisa , Yamanaka Nobuaki
Published: January 2020

Background: Renin-angiotensin-aldosterone system blockers are known to reduce hypertrophy of vascular smooth muscle cells (SMCs) in hypertensive cases. However, we have reported marked proliferative changes of renal afferent arteriolar SMCs in rats induced by a long-term administration of angiotensin II type 1 receptor blockers (ARBs) and an angiotensin-converting enzyme inhibitor (ACEI). In this study, we examined the morphological changes of afferent arteriolar walls in human kidneys with or without ARBs/ACEIs. Methods: Forty-four wedge resections were taken from patients aged 45–74 years from 92 nephrectomized kidneys due to malignancy at Toho University Omori Medical Center between 2013 and 2016. They were divided into the following three groups: 18 hypertensive patients treated with antihypertensive agents including ARBs or ACEIs (the HTARB group), 6 hypertensive patients treated with calcium channel blockers without ARBs/ACEIs (the HTCCB group), and 20 normotensive patients (the normotensive group) as a control. Cases expecting vascular changes such as diabetes were excluded. In each case renal arterioles were measured as the ratio of inner/outer arteriolar diameter, and pathologists estimated morphological abnormal changes, scoring each specimen independently. Results: The ratio in the HTARB group was 0.39 ± 0.05 (mean ± SD), and was significantly the lowest among the three groups (0.46 ± 0.02 in the HTCCB, 0.53 ± 0.02 in the normotensive group; p = 0.0107 vs. HTCCB, p = 0.00001 vs. normotensive). The ratio in the three groups significantly correlated with the estimated glomerular filtration rate (r = 0.4915, p < 0.0007). The afferent arteriolar SMCs in the HTARB group frequently showed marked proliferative and irregular changes. The score of SMC abnormalities estimated regarding the proliferation, irregularity of the arrangement, and size in hilar afferent arteriolar SMCs was highest in the HTARB group and showed statistical significance (p = 0.0088, p = 0.00001, and p = 0.025 versus other two groups). Conclusions: We consider that these morphological changes in arterioles are induced by ARBs/ACEIs. These changes could induce an important suppression of glomerular hyperfiltration and could lead to glomerular ischemia. However, the clinical consequences of these morphological changes in correlation with ARBs/ACEIs were not sufficiently clear and require further analysis. We should consider renal arteriolar morphological changes when using ARBs/ACEIs.
Fractures due to Aromatase Inhibitor Therapy for Breast Cancer: A Real-World Analysis of FAERS Data in the Past 15 Years
Authors: Song Yu , Xu Ya-li , Lin Yan , Zhao Bin , Sun Qiang
Published: January 2020

Introduction: The adverse effect of fractures by different aromatase inhibitor (AI) drugs has not been thoroughly assessed in real-world studies. Objective: To assess the adverse events of fractures of real-world breast cancer patients caused by AI therapy through the Food and Drug Administration Adverse Event Reporting System (FAERS) database. Methods: The FAERS data from January 2004 to December 2018 were sorted out and analyzed for correlations between fractures and AI use. Disproportionate analysis and Bayesian analysis were adopted to quantify the signal, the association between the AIs and fractures. The onset time and outcome of fractures after different AI regimens were also compared. Results: Out of 23,064 adverse reports, 657 fracture reports (2.85%) were analyzed. Anastrozole showed a positive association with 4 detection methods, while letrozole and exemestane did so with 2. More exemestane-related reports (44.62%) resulted in initial or prolonged hospitalization than anastrozole (30.12%, p = 0.013) and letrozole (29.43%, p = 0.006). The fracture onset time showed no significant difference among anastrozole, letrozole, and exemestane (median onset time: 46.95, 34.25, and 40.58 months, respectively; p = 0.236). Conclusions: Anastrozole should be prescribed with more medical care. Analysis of FAERS data identified fracture risk tendencies with AI regimens, which supported continuous monitoring, risk evaluations, and further comparative studies.
Next Generation Sequencing-Based Fetal ABO Blood Group Prediction by Analysis of Cell-Free DNA from Maternal Plasma
Authors: Rieneck Klaus , Egeberg Hother Christoffer , Clausen Frederik Banch , Jakobsen Marianne Antonius , Bergholt Thomas , Hellmuth Ellinor , Grønbeck Lene , Dziegiel Morten Hanefeld
Published: January 2020

Introduction: ABO blood group incompatibility between a pregnant woman and her fetus as a cause of morbidity or mortality of the fetus or newborn remains an important, albeit rare, risk. When a pregnant woman has a high level of anti-A or anti-B IgG antibodies, the child may be at risk for hemolytic disease of the fetus and newborn (HDFN). Performing a direct prenatal determination of the fetal ABO blood group can provide valuable clinical information. Objective: Here, we report a next generation sequencing (NGS)-based assay for predicting the prenatal ABO blood group. Materials and Methods: A total of 26 plasma samples from 26 pregnant women were tested from gestational weeks 12 to 35. Of these samples, 20 were clinical samples and 6 were test samples. Extracted cell-free DNA was PCR-amplified using 2 primer sets followed by NGS. NGS data were analyzed by 2 different methods, FASTQ analysis and a grep search, to ensure robust results. The fetal ABO prediction was compared with the known serological infant ABO type, which was available for 19 samples. Results: There was concordance for 19 of 19 predictable samples where the phenotype information was available and when the analysis was done by the 2 methods. For immunized pregnant women (n = 20), the risk of HDFN was predicted for 12 fetuses, and no risk was predicted for 7 fetuses; one result of the clinical samples was indeterminable. Cloning and sequencing revealed a novel variant harboring the same single nucleotide variations as ABO*O.01.24 with an additional c.220C>T substitution. An additional indeterminable result was found among the 6 test samples and was caused by maternal heterozygosity. The 2 indeterminable samples demonstrated limitations to the assay due to hybrid ABO genes or maternal heterozygosity. Conclusions: We pioneered an NGS-based fetal ABO prediction assay based on a cell-free DNA analysis from maternal plasma and demonstrated its application in a small number of samples. Based on the calculations of variant frequencies and ABO*O.01/ABO*O.02 heterozygote frequency, we estimate that we can assign a reliable fetal ABO type in approximately 95% of the forthcoming clinical samples of type O pregnant women. Despite the vast genetic variations underlying the ABO blood groups, many variants are rare, and prenatal ABO prediction is possible and adds valuable early information for the prevention of ABO HDFN.
Análise do Timi Risk score em pacientes com infarto agudo do miocárdio com supradesenvolvimento do segmento ST após 6 meses
Authors: Ketzer Bernardo Mazzini , Gil Érlon , Rodrigues Gustavo Reis , Kawata Marcelo Fukuhara , Gun Carlos , Luca Fábio Augusto de
Published: January 2020

Introdução: O escore de TIMI RISK (TR) para infarto agudo do miocárdio com supradesnivelamento do segmento ST (IAM) foi descrito originalmente por Morrow et al. (2000),baseado em 8 variáveis. Foi utilizado no estudo In TIME II como preditor de morte em 30m dias e diversos estudos têm relatado com sucesso o TR como índice prognóstico para IAM, no entanto poucos relatos avaliam a evolução tardia desses pacientes e relação como o escore. Objetivo: Avaliar a evolução em 6 meses dos pacientes internados em Hospital Escola com IAM e sua relação com a estradição do TR.Casuística e Método: Foram acompanhados ambulatorialmente em hospital escola, 89 pacientes, durante6 meses após determinação inicial do escore do TR realizado durante internação por IAM. Foram avaliados os seguintes parâmetros: óbito, reinternação por evento cardiovascular e necessidade de revascularização. Divididos em 3 grupos de acordo com o escore: Grupo I (0, 1, 2); Grupo II (3, 4, 5);Grupo III (> 5), foram submetidos à análise estatística pelo método de Qui-Quadrado. Resultados: Óbito, revascularização e reinternação respectivamente: GI- 4,1%, 20%, 25%; GII- 10%, 30% e GIII- 52%, 48%, 60%. Conclusão: O escore de TR manteve significativo aumento de eventos nos grupos II e III em relação ao grupo I; mostrando a possível aplicabilidade do escore também como preditor a longo prazo (6 meses).
O aprendizado baseado em problemas - PBL
Authors: Tibério Iolanda De F. L. Calvo , Atta José Antonio , Lichtenstein Arnaldo
Published: January 2020

O Aprendizado Baseado em Problemas (ou “Problem Based Learning – PBL”) é uma técnica de ensino que utiliza problemas (que podem ser casos clínicos, problemas epidemiólogicos, dilemas éticos etc) a serem discutidos em um grupo relativamente pequeno de alunos. Em aplicação em vários centros universitários desde a década de 1960, dois grandes centros são referência no mundo todo: asuniversidades de McMaster, no Canadá e a de Maastricht, na Holanda. Nesses grupos, chamados grupos tutoriais, todos dão sua contribuição e, ao final, objetivos de estudo são delimitados. Depois, fora do grupo tutorial, os objetivos são estudados utilizando os meios à disposição (biblioteca, consulta a especialistas, Internet) sendo rediscutidos em outro grupo tutorial. Currículos baseados nessa técnica deensino são habitualmente estruturados em blocos e não mais em disciplinas tradicionais, além de contarem com espaços livres na grade curricular para que o aluno possa estudar. Apesar das vantagens sobre os métodos tradicionais como por exemplo tornar o aluno mais independente na busca do conhecimento, permitir maior integração entre as disciplinas, implicar em capacitação constante do corpo docente,aparentemente os alunos formados por esse método não apresentam vantagens sobre os alunos de métodostradicionais nas provas e concursos realizados imediatamente ao final do curso médico, mas alguns estudos sugerem maior retenção do conhecimento após um ano.
Currículo do curso de medicina da Faculdade de Medicina da Universidade de São Paulo
Authors: Martins Milton Arruda
Published: January 2020

A primeira turma a ter tido contato com o currículo nuclear está se formando, e esse fato suscita vários questionamentos. Para respondê-los, ainda que em parte, uma avaliação está em curso. O currículo nuclear possibilitou aos estudantes oportunidade de ampliar e individualizar sua formaçãoacadêmica, sem, no entanto, deixar de atender alguns requisitos, como a ênfase na formação geral. Outros pontos considerados foram a centralização no aluno, a atividade didática, a relação professoraluno e a integração das áreas básica e clínica. Alguns foram sucedidos, outros não.
Major Adverse Cardiovascular Events Associated With Postoperative Atrial Fibrillation After Noncardiac Surgery
Authors: AlTurki Ahmed , Marafi Mariam , Proietti Riccardo , Cardinale Daniela , Blackwell Robert , Dorian Paul , Bessissow Amal , Vieira Lucy , Greiss Isabelle , Essebag Vidal , Healey Jeff S. , Huynh Thao
Published: January 2020

Background:

Postoperative atrial fibrillation (POAF) is a frequent occurrence after noncardiac surgery. It remains unclear whether POAF is associated with an increased risk of major adverse events. We aimed to elucidate the risk of stroke, myocardial infarction, and death associated with POAF following noncardiac surgery by a meta-analysis of randomized controlled studies and observational studies.

Methods:

We searched electronic databases from inception up to August 1, 2019 for all studies that reported stroke or myocardial infarction in adult patients who developed POAF following noncardiac surgery. We used random-effects models to summarize the studies.

Results:

The final analyses included 28 studies enrolling 2 612 816 patients. At 1-month (10 studies), POAF was associated with an ≈3-fold increase in the risk of stroke (weighted mean 2.1% versus 0.7%; odds ratio [OR], 2.82 [95% CI, 2.15–3.70];
P
<0.001). POAF was associated with ≈4-fold increase in the long-term risk of stroke with (weighted mean, 2.0% versus 0.6%; OR, 4.12 [95% CI, 3.32–5.11];
P
≤0.001) in 8 studies with ≥12-month follow-up. There was a significant overall increase in the risk of stroke and myocardial infarction associated with POAF (weighted mean, 2.5% versus 0.9%; OR, 3.44 [95% CI, 2.38–4.98];
P
<0.001) and (weighted mean, 12.6% versus 2.7%; OR, 4.02 [95% CI, 3.08–5.24];
P
<0.001), respectively. Furthermore, POAF was associated with a 3-fold increase in all-cause mortality at 30 days (weighted mean, 15.0% versus 5.4%; OR, 3.36 [95% CI, 2.13–5.31];
P
<0.001).

Conclusions:

POAF was associated with markedly higher risk of stroke, myocardial infarction, and all-cause mortality following noncardiac surgery. Future studies are needed to evaluate the impact of optimal cardiovascular pharmacotherapies to prevent POAF and to decrease the risk of major adverse events in these high-risk patients.
When Sinus Tachycardia Becomes Too Much
Authors: Stewart Julian M. , Medow Marvin S. , Visintainer Paul , Sutton Richard
Published: January 2020

Background:

Upright posture reduces venous return, stroke volume, and cardiac output (CO) while causing reflex sinus rate (heart rate [HR]) increase. Yet, in inappropriate sinus tachycardia (IST), postural tachycardia syndrome (POTS), and vasovagal syncope (VVS), symptomatic excessive HR occurs. We hypothesized that CO reaches maximum as function of HR in all.

Methods:

We recruited 12 healthy controls, 9 IST, 30 VVS, and 30 POTS patients (13-23years) selected randomly by disorder not by HR, each fulfilled appropriate diagnostic criteria. Subjects were instrumented for electrocardiography, beat-to-beat blood pressure, respiratory rate, CO-Modelflow algorithm, and central blood volume from impedance cardiography; 10-minute data were collected supine; subjects were tilted head-up for ≤10 minutes. We computed phase differences, ΔΦ, between fluctuations of HR (ΔHR) and CO (ΔCO) tabulating data when phases were synchronized, determined by a squared nonlinear phase synchronization index >0.5, describing extent/validity of CO/HR coupling. We graphed results supine, 1-minute post-tilt-up, mid-tilt, and pre-tilt-down using polar coordinates (HR—radius, ΔΦ—angle) plotting cos(ΔΦ) versus HR to determine if transition HR exists at which in-phase shifts to antiphase above which CO decreases when HR further increases.

Results:

At baseline HR, diastolic and mean arterial pressures in IST and POTS were higher versus controls. Upright HR increased most in POTS then IST and VVS, with diverse changes in CO, SVR, and central blood volume. Each patient grouping was separately and collectively analyzed for HR change showing transition from in-phase to anti-phase (ΔΦ) as HR increased: HR
transition
=115±6 (IST), 123±8 (POTS), 124±7 (VVS),
P
=ns. Controls never reached transitional HR.

Conclusions:

Excessive HR independently and equivalently reduces upright CO, in IST, POTS, and VVS.
Chronobiological Influence Over Cardiovascular Function
Authors: Rana Samir , Prabhu Sumanth D. , Young Martin E.
Published: January 2020

Essentially all biological processes fluctuate over the course of the day, observed at cellular (eg, transcription, translation, and signaling), organ (eg, contractility and metabolism), and whole-body (eg, physical activity and appetite) levels. It is, therefore, not surprising that both cardiovascular physiology (eg, heart rate and blood pressure) and pathophysiology (eg, onset of adverse cardiovascular events) oscillate during the 24-hour day. Chronobiological influence over biological processes involves a complex interaction of factors that are extrinsic (eg, neurohumoral factors) and intrinsic (eg, circadian clocks) to cells. Here, we focus on circadian governance of 6 fundamentally important processes: metabolism, signaling, electrophysiology, extracellular matrix, clotting, and inflammation. In each case, we discuss (1) the physiological significance for circadian regulation of these processes (ie, the good); (2) the pathological consequence of circadian governance impairment (ie, the bad); and (3) whether persistence/augmentation of circadian influences contribute to pathogenesis during distinct disease states (ie, the ugly). Finally, the translational impact of chronobiology on cardiovascular disease is highlighted.
Kakameganula, a new name for the preoccupied Kakamega Dawidowicz & Wesołowska, 2016 (Araneae: Salticidae)
Authors: WESOŁOWSKA WANDA
Published: January 2020

Dawidowicz & Wesołowska (2016) proposed the jumping spider genus Kakamega for the type species Kakamega holmi Dawidowicz & Wesołowska, 2016, probably endemic to the Kakamega Forest of Kenya, a remnant of the Guineo-Congolian tropical rainforest.
Chaetotaxy and morphometry of the head capsule and head appendages of the genus Derallus Sharp (Coleoptera: Hydrophilidae)
Authors: RODRIGUEZ GEORGINA , TORRES PATRICIA L. M. , ARCHANGELSKY MIGUEL
Published: January 2020

The primary and secondary chaetotaxy of the head capsule and head appendages of the three larval instars of the water scavenger beetle genus Derallus Sharp are described for the first time based on two species: D. angustus Sharp and D. paranensis Oliva. Morphometric characters derived from the head capsule and mouthparts are included, together with detailed illustrations of all characters. Chaetotaxy of these larvae is compared with that of Regimbartia attenuata (Fabricius), another species belonging to the Derallus-clade of Berosini.
Comparing the Rates of Misconduct Between Private and Public Prisons in Texas
Authors: El Sayed Sarah A. , Morris Robert G. , DeShay Rashaan A. , Piquero Alex R.
Published: January 2020

Mass incarceration has led to an increased reliance on private prisons. Yet, there is little evidence regarding the extent to which public safety and misconduct patterns differ across private versus public prisons. Combining data from prisoners in the State of Texas within a counterfactual research design, the current study examines differences in the likelihood of engaging in misconduct among comparable male inmates sentenced to a private over a public prison unit. Findings indicate there are no significant differences in the amount of misconduct committed by inmates in either public or private institutions—with the exception of physical violence. Inmates assigned to private facilities were 10% less likely to engage in institutional violence compared with similarly situated inmates assigned to public facilities.
The decentered translation of management ideas: Attending to the conditioning flow of everyday work practices
Authors: Hultin Lotta , Introna Lucas D , Mähring Magnus
Published: January 2020

Based on a study of Lean management practices at the Swedish Migration Board, we develop a novel theoretical understanding of the translation of management ideas. We show how translation, rather than being reduced to a network of human intentions and actions governing the transformation of organizational practices, can instead be understood as a historically contingent, situated flow of mundane everyday work practices through which social and material translators simultaneously become translated, conditioned to be and act in certain ways. We show how prior actor-centric accounts of translation of management ideas can be understood as performative consequences of a conceptual vocabulary inherited from Callon and Latour. Contrasting this, the non-actor-centric vocabulary of social anthropologist Tim Ingold allows us to background the intentional human actor and foreground the flow of mundane, situated practices. In adopting this vocabulary, we capture how the flow of practices conditions subjects and objects to become enacted as well as act, and develop an understanding of translation as occurring within, rather than distinct from, these practices. In essence, our novel view of translation emphasizes how management ideas are radically unstable, and subject to alteration through the flow of practices rather than as a result of deliberate implementation efforts.
Periodic impulse signal separation based on resonance-based sparse signal decomposition and its application to the fault detection of rolling bearing
Authors: Juan Du , Yan Lu , Xian Tao , Yu Zheng , Chu Chen Guo
Published: January 2020

The main purpose of the paper is to propose a new method to achieve separating periodic impulse signal among multi-component mixture signal and its application to the fault detection of rolling bearing. In general, as local defects occur in a rotating machinery, the vibration signal always consists of periodic impulse components along with other components such as harmonic component and noise; impulse component reflects the condition of rolling bearing. However, different components of multi-component mixture signal may approximately have same center frequency and bandwidth coincides with each other that is difficult to disentangle by linear frequency-based filtering. In order to solve this problem, the author introduces a proposed method based on resonance-based sparse signal decomposition integrated with empirical mode decomposition and demodulation that can separate the impulse component from the signal, according to the different Q-factors of impulse component and harmonic component. Simulation and application examples have proved the effectiveness of the method to achieve fault detection of rolling bearing and signal preprocessing.
France’s déclassement in the Eurozone
Authors: Giurlando Philip
Published: January 2020

In France, the adoption of the euro was partly motivated by the desire for equality with Germany, but asymmetry has increased in terms of economic prowess and international status, leading to a sense of déclassement. This paper identifies links between France’s status reduction, a consequent feeling of humiliation, and the foreign policy positions associated with that collective emotion. Evidence of France’s déclassement includes macroeconomic trends, semi-structured interviews with a sample of elites, the secondary literature, and the domestic political disputes that have emerged as a result of this reduction of national status. The paper also systematically compares France to Italy, as in many ways it is similar to that country, but with one key difference: the political forces which have been loudest about Italy’s humiliation vis-à-vis Germany obtained power and governed from May 2018 to August 2019. Their orientations and positions provide a peek into the kinds of international political decisions associated with both déclassement and humiliation, and provide further evidence on the links between status reduction, group-level emotion, and inter-group behaviour.
Reuse of open data in Quebec: from economic development to government transparency
Authors: Boudreau Christian
Published: January 2020

Based on the history of open data in Quebec, this article discusses the reuse of these data by various actors within society, with the aim of securing desired economic, administrative and democratic benefits. Drawing on an analysis of government measures and community practices in the field of data reuse, the study shows that the benefits of open data appear to be inconclusive in terms of economic growth. On the other hand, their benefits seem promising from the point of view of government transparency in that it allows various civil society actors to monitor the integrity and performance of government activities. In the age of digital data and networks, the state must be seen not only as a platform conducive to innovation, but also as a rich field of study that is closely monitored by various actors driven by political and social goals.

Points for practitioners

Although the economic benefits of open data have been inconclusive so far, governments, at least in Quebec, must not stop investing in opening up their data. In terms of transparency, the results of the study suggest that the benefits of open data are sufficiently promising to continue releasing government data, if only to support the evaluation and planning activities of public programmes and services.
Citizens’ Satisfaction with Government in a Highly Corrupt Public Life: Role of Trust in Democracy and Civil Society Participation in Somalia
Authors: Mishra Santap Sanhari , Abdullahi Mohamud Mohamed
Published: January 2020

Corruption is the biggest obstacle in the way of human development. In a highly corrupt public life, citizens’ satisfaction seems to be a mirage. But can citizens’ satisfaction be possible even if there is less chance of sounding the death knell for corruption? To investigate this, this study examines the mediating effect of trust in democracy and civil society participation in the relationship of corruption and citizens’ satisfaction in the context of Somalia, considered to be the most corrupt country in the world. Using a survey, a total of 205 valid responses from public service users in Somalia were put into confirmatory factor analysis. The empirical results show the partial mediation of civil society participation and trust in democracy; however, civil society participation is more effective than trust in democracy in mediating the relationship of corruption and citizens’ satisfaction, because of less negative indirect effect.
Dental RECUR Randomized Trial to Prevent Caries Recurrence in Children
Authors: Pine C.M. , Adair P.M. , Burnside G. , Brennan L. , Sutton L. , Edwards R.T. , Ezeofor V. , Albadri S. , Curnow M.M. , Deery C. , Hosey M.T. , Willis-Lake J. , Lynn J. , Parry J. , Wong F.S.L.
Published: January 2020

The purpose of this study was to determine the efficacy of a dental nurse–delivered intervention—the Dental RECUR Brief Negotiated Interview for Oral Health (DR-BNI)—in reducing the recurrence of dental caries in children who have a primary tooth extracted. It was based on a 2-arm multicenter randomized controlled trial with blinded outcome assessment. Participants were 5- to 7-y-old children ( n = 241) scheduled to have primary teeth extracted in 12 UK centers. Test intervention parents ( n = 119) received DR-BNI led by trained dental nurses. DR-BNI is a 30-min structured conversation informed by motivational interviewing with a forward focus to prevent future caries. Preventive goals are agreed, and a review appointment is made with child’s general dental practitioner, who is advised to treat the child as being at high caries risk. The control intervention ( n = 122) was a parent-nurse conversation about child’s future tooth eruption, with advice given to visit a general dental practitioner as usual. At baseline, the DR-BNI group’s mean dmft was 6.8, and the control group’s was 6.3. A median of 5 teeth were extracted, mainly under general anesthesia. Final dental assessments were conducted by a single examiner visiting 189 schools 2 y after intervention; 193 (80%) of 241 children were examined. In the control group, 62% developed new caries in teeth that were caries-free or unerupted at baseline, as compared with 44% in the test group, a significant reduction ( P = 0.021). The odds of new caries experience occurring were reduced by 51% in the DR-BNI group as compared with control. There was a 29% decrease in the relative risk of new caries experience in the DR-BNI group as compared with control. This single low-cost, low-intensity intervention was successful in significantly reducing the risk of recurrence of dental caries in children. This trial has implications for changing pediatric dental practice internationally. Training in and implementation of a motivational interviewing–informed brief intervention provides opportunities for dental nurses to facilitate behavior change improving the oral health of children at high caries risk (ISRCTN 24958829).
Oedipus Rex as a philosophical and political strategy
Authors: Moreno Pestaña José Luis
Published: January 2020

This article studies Michel Foucault’s interpretation of the tragedy Oedipus Rex. The analysis seeks to uncover the various intellectual strategies around his study. First, Foucault takes a position in the political debate about prisons in France in the early 1970s. Second, his analysis of the tragedy contributes to position his work in the field of the philosophical history of truth, by singularising his project and separating it from the dominant models of the history of philosophy. Third, Foucault aims to differentiate himself from the results of the historical work of the Paris School. This article analyses how Foucault depends on these interpretations and how it helps him to acquire philosophical relevance. Through the sociology of intellectual history’s perspective, the article elaborates the contributions and limits of Foucault’s perspective.
Community-driven disorder reduction: Crime prevention through a clean and green initiative in a legacy city
Authors: Pizarro Jesenia M. , Sadler Richard C. , Goldstick Jason , Turchan Brandon , McGarrell Edmund F. , Zimmerman Marc A.
Published: January 2020

This study examines the effects of a neighbourhood greening and beautification strategy called Clean & Green on crime prevention and reduction. Point level data for all Part I index crimes and Clean & Green efforts in the study area from 2005 to 2014 are analysed using spatial and linear regression with two key modifications: (1) controlling for temporal and spatial dependencies between points; and (2) allowing for potentially non-linear temporal trends in the effect of cumulative greening. To accommodate those modifications, generalised additive models (GAMs) were employed. The analyses of violent and property crimes suggest that greening efforts are increasingly protective over time. The findings demonstrate that the elimination of blight and disorder via neighbourhood greening and beautification efforts can be an effective tool for crime prevention and control in communities.
Formation Mechanisms of Stalinist Oil-Shale Mining and Industrial Towns in East Estonia: Soviet Nuclear Needs and Local Ambitions
Authors: Sultson Siim
Published: January 2020

Planning of oil-shale mining and industrial towns Kohtla-Järve, Jõhvi, Sillamäe, Ahtme, Sompa, Kukruse, Kiviõli, Kohtla-Nõmme, and Viivikonna was caused by Soviet Union’s need for mineral resources, nuclear arms race, army, industry, and economy. East Estonian region gained strategic importance for the Soviet Union already in 1940. Although these towns were planned mostly by nonlocal architects and stately architectural firms, for instance, Stalinist central gridlines and central urban ensembles of Kohtla-Järve and Sillamäe were designed under the guidance of local architect Harald Arman. As a head of the Department of Architecture of the Estonian SSR, he processed both masterplans and construction plans of those towns within ambitious planning of oil-shale region during the mid-1940s and early-1950s. Those factors established urban planning principles and a pattern of East Estonian oil-shale mining and industrial towns.