bluuebunny/crossref_metadata_2025 huggingface dataset:
Rational Application of First‐Line EGFR‐TKIs Combined with Antiangiogenic Inhibitors in Advanced EGFR‐Mutant Non‐Small‐Cell Lung Cancer: A Systematic Review and Meta‐Analysis
Authors: Ma Jie-Tao , Guo Yi-Jia , Song Jun , Sun Li , Zhang Shu-Ling , Huang Le-Tian , Jing Wei , Zhao Jian-Zhu , Han Cheng-Bo
Published: January 2021

Purpose. A meta‐analysis of randomized controlled trials (RCTs) was conducted to compare the difference in efficacy and safety between epidermal growth factor receptor‐tyrosine kinase inhibitors (EGFR‐TKIs) with antiangiogenic inhibitors (A + T) and EGFR‐TKI monotherapy in patients with treatment‐naïve advanced EGFR‐mutant non‐small‐cell lung cancer (NSCLC). Methods. PubMed, Embase, Web of Science, and Cochrane electronic databases were searched for relevant RCTs. Meeting abstracts were also reviewed to identify appropriate studies. The endpoints included progression‐free survival (PFS), overall survival (OS), 1‐ and 2‐year OS rates, objective response rate (ORR), and grade ≥ 3 adverse events. All pooled outcomes were expressed using hazard ratios (HRs) or relative risk ratios (RRs). Results. Data were collected from six eligible RCTs, which included 1,244 participants (619 in the A + T group and 625 in the TKI alone group). PFS was significantly improved with A + T compared to TKI alone (HR = 0.60; P < 0.01) regardless of EGFR mutation types (exon 19 deletion or L858R) and brain metastasis status (with or without brain metastases). There was no significant difference in median OS between the A + T and TKI alone groups (HR = 0.933; P = 0.551) regardless of EGFR mutation type. The ORR for A + T combination therapy was significantly increased compared to TKI monotherapy in exon 19 deletion subgroups (RR = 0.774; P = 0.008). There was no difference in the positive rates of acquired T790M mutation between the two groups (RR = 0.967; P = 0.846). More patients in the TKI alone group received a variety of subsequent systemic treatments than those in the A + T group (RR = 0.881; P = 0.002). Conclusion. Addition of antiangiogenic inhibitors to first‐line EGFR‐TKI therapy significantly reduced the risk of disease progression for patients with advanced EGFR‐mutant NSCLC regardless of EGFR mutation type and brain metastasis status. The lack of OS benefit may be explained by differences in subsequent treatments rather than drug resistance mechanisms.
A Description and Examination of Fluorescence in Nine North American Firefly Species (Coleoptera: Lampyridae)
Authors: Wilcox Aidan
Published: January 2021

Fluorescence across the family Lampyridae has been documented sporadically but not comprehensively in formal research. Fireflies (Coleoptera: Lampyridae), best known for their bioluminescence, are also fluorescent. This fluorescence has been documented in several genera within the clade but is still an often overlooked aspect of firefly physiology in the common understanding of the species. To this end, the purpose of this study was to document and describe the fluorescence in nine species of North American fireflies, across three genera. Each species was photographed and a description of the fluorescent pattern was provided, as well as measurements of the specific spectral sensitivity of the fluorescent excitation and emission wavelengths. These data are intended to provide an identification guide of sorts to different firefly fluorescence, as well as documenting definitively its presence in several firefly genera.
Research on the Influence of New Media Technology on Internet Short Video Content Production under Artificial Intelligence Background
Authors: Lu Zhiqin , Nam Inyong
Published: January 2021

With the rapid development of the Internet and smart phone technology, a large number of short videos are shared through social platforms. Therefore, video content analysis is a very important and popular work in machine learning and artificial intelligence currently. However, it is very difficult to analyze all aspects of video content originally produced by large‐scale users. How to screen out bad and illegal content from short videos published by a large number of users, select high‐quality videos to share with other users, and improve the quality of video on the distribution platform of the entire user is a top priority. Based on this background, this paper focuses on optimizing video auditing to provide basic features for algorithm judgment, supporting original content and increasing the distribution of new content, and strengthening manual intervention combining algorithm recommendation with manual recommendation. Four major aspects of the artificial training algorithm model discuss the optimization effect of artificial intelligence on the algorithm in order to provide some guidance for the sustainable and healthy development of mobile short video.
Is There a Role for Tranexamic Acid in Upper GI Bleeding? A Systematic Review and Meta-Analysis
Authors: Burke Eoghan , Harkins Patricia , Ahmed Ibrahim
Published: January 2021

Introduction. Upper gastrointestinal (GI) bleeding is associated with increased morbidity and mortality. Tranexamic acid (TXA) is an antifibrinolytic agent which is licensed in the management of haemorrhage associated with trauma. It has been suggested that tranexamic acid may be able to play a role in upper GI bleeding. However, there is currently no recommendation to support this. Aim. The aim of this study was to synthesise available evidence of the effect of TXA on upper GI bleeding. Methods and Materials. A systematic review was conducted. PubMed, EMBASE, and Cochrane Central Register of Controlled Trials (CENTRAL) were searched for relevant studies. A random effects meta-analysis was performed to determine the risk ratio of primary and secondary outcomes pertaining to the use of TXA in upper GI bleeding. Results. A total of 8 studies were included in this systematic review. The total number of patients in all studies was 12994 including 4550 females (35%) and 8444 males (65%). The mean age of participants in 6 of the studies was 59.3; however the mean age for either intervention or placebo group was not reported in two of the studies. All studies reported on the effect of TXA on mortality, and the risk ratio was 0.95; however, with the 95% CI ranging from 0.80 to 1.13, this was not statistically significant. 6 of the studies reported on rebleeding rate, the risk ratio was 0.64, and with a 95% CI ranging from 0.47 to 0.86, this was statistically significant. 3 of the studies reported on the risk of adverse thromboembolic events, and the risk ratio was 0.93; however, the 95% CI extended from 0.62 to 1.39 and so was not statistically significant. 7 of the studies reported on the need for surgery, and the risk ratio was 0.59 and was statistically significant with a 95% CI ranging from 0.38 to 0.94. Conclusion. In conclusion, the use of TXA in upper GI bleeding appears to have a beneficial effect in terms of decreasing the risk of re-bleeding and decreasing the need for surgery. However, we could not find a statistically significant effect on need for blood transfusions, risk of thromboembolic events, or effect on mortality. Future randomised controlled trials may elucidate these outcomes.
Improvement of the Communication between RFID Sensor Network Devices Used to Control and Monitor a Building
Authors: Bou-El-Harmel Abdelhamid , Benbassou Ali , Belkadid Jamal
Published: January 2021

In the RFID sensor network (RSN), the devices communicate with each other by RF waves using the antennas through a propagation channel. A poor communication between these devices results in either a significant economic loss or security threats. The communication problems can have several origins depending on the type of antenna used and the nature of the propagation channel. In this work, our objective is to limit the communication problems between the nodes of this network that are linked to the characteristics of an indoor propagation channel. The goal is to predict the channel characteristics using the 3D ray tracing method in order to select the appropriate transmission parameters such as transmission power and duration of a symbol. To achieve this, we have modeled a building that is sectioned as a propagation channel where network devices are deployed for control and monitoring. The communication was made at 915 MHz using the quasi‐isotropic 3D cubic antenna that we designed as well as a conventional dipole antenna in order to compare the results. We have found that the use of the 3D cubic antenna gives several advantages to the RFID sensor network compared to the most commonly used conventional dipole antenna, such as a transmission power of 0 dBm which automatically leads to an increase in the lifetime of the devices, as well as a minimum symbol duration of around 219.78 ns which gives a high bit rate.
Energy‐Efficient Virtual Network Embedding Algorithm Based on Hopfield Neural Network
Authors: He Mengyang , Zhuang Lei , Yang Sijin , Zhang Jianhui , Meng Huiping
Published: January 2021

To solve the energy‐efficient virtual network embedding problem, this study proposes an embedding algorithm based on Hopfield neural network. An energy‐efficient virtual network embedding model was established. Wavelet diffusion was performed to take the structural feature value into consideration and provide a candidate set for virtual network embedding. In addition, the Hopfield network was used in the candidate set to solve the virtual network energy‐efficient embedding problem. The augmented Lagrangian multiplier method was used to transform the energy‐efficient virtual network embedding constraint problem into an unconstrained problem. The resulting unconstrained problem was used as the energy function of the Hopfield network, and the network weight was iteratively trained. The energy‐efficient virtual network embedding scheme was obtained when the energy function was balanced. To prove the effectiveness of the proposed algorithm, we designed two experimental environments, namely, a medium‐sized scenario and a small‐sized scenario. Simulation results show that the proposed algorithm achieved a superior performance and effectively decreased the energy consumption relative to the other methods in both scenarios. Furthermore, the proposed algorithm reduced the number of open nodes and open links leading to a reduction in the overall power consumption of the virtual network embedding process, while ensuring the average acceptance ratio and the average ratio of the revenue and cost.
Worldwide Prevalence of Occupational Exposure to Needle Stick Injury among Healthcare Workers: A Systematic Review and Meta-Analysis
Authors: Mengistu Dechasa Adare , Tolera Sina Temesgen , Demmu Yohannes Mulugeta
Published: January 2021

Background. Healthcare workers are at high risk of occupational exposure to needle stick injury worldwide. Occupational exposure to needle stick injury represents the most common sources of infection such as hepatitis B virus, hepatitis C virus, and human immunodeficiency virus. Thus, this review aimed to determine the career time and previous one-year global pooled prevalence of occupational exposure to needle stick injury among healthcare workers. Methods. The review considered articles written in English language and published from 2012 to 2020. The articles were searched using nine electronic databases (PubMed, Google Scholar, CINAHL, MEDLINE, Cochrane library, Web of Science, SCOPUS, MedNar, and ScienceDirect) using a combination of Boolean logic operators (AND, OR, and NOT), Medical Subject Headings, and keywords. Quality assessment was performed to determine the relevance of the articles using Joanna Briggs Institute critical appraisal tools. Several steps of assessment and evaluation were taken to select and analyze the relevant articles. Results. The worldwide pooled prevalence of needle stick injuries among healthcare workers during career time and previous one year was 56.2% (95% CI: 47.1, 64.9) and 32.4% (95% CI: 22.0, 44.8), respectively. The career time pooled prevalence of needle stick injuries based on the socioeconomic development and study area was 54.8% and 55.1%, respectively, and one-year pooled prevalence of needle stick injury was 26.0% and 20.9%. Conclusion. The review found a high prevalence of occupational exposure to needle stick injury among healthcare workers and suggests the need to improve occupational health and safety services in the healthcare systems.
Predicting the Survival Probability of Neuroendocrine Tumor Populations: Developing and Evaluating a New Predictive Nomogram
Authors: Chen Jian-Xian , Lin Yan , Meng Yi-Liang , Zhao Ai-Xia , Huang Xiao-Juan , Liang Rong , Li Yong-Qiang , Liu Zhi-Hui
Published: January 2021

Purpose. The purpose of this study was to develop and initially validate a nomogram model in order to predict the 3‐year and 5‐year survival rates of neuroendocrine tumor patients. Methods. Accordingly, 348 neuroendocrine tumor patients were enrolled as study objects, of which 244 (70%) patients were included in the training set to establish the nomogram model, while 104 (30%) patients were included in the validation set to verify the robustness of the model. First, the variables related to the survival rate were determined by univariable analysis. In addition, variables that were sufficiently significant were selected for constructing the nomogram model. Furthermore, the concordance index (C‐index), receiver operating characteristic (ROC), and calibration curve analysis were used to evaluate the performance of the proposed nomogram model. The survival analysis was then used to evaluate the return to survival probability as well as the indicators of constructing the nomogram model. Results. According to the multivariable analysis, lymphatic metastasis, international normalized ratio (INR), prothrombin time (PT), tumor differentiation, and the number of tumor metastases were found to be independent predictors of survival rate. Moreover, the C‐index results demonstrated that the model was robust in both the training set (0.891) and validation set (0.804). In addition, the ROC results further verified the robustness of the model either in the training set (AUC = 0.823) or training set (AUC = 0.768). Furthermore, the calibration curve results showed that the model can be used to predict the 3‐year and 5‐year survival probability of neuroendocrine tumor patients. Meaningfully, five variables were found: lymphatic metastasis (p = 0.0095), international standardized ratio (p = 0.024), prothrombin time (p = 0.0036), tumor differentiation (p = 0.0026), and the number of tumor metastases (p = 0.00096), which were all significantly related to the 3‐year and 5‐year survival probability of neuroendocrine tumor patients. Conclusion. In summary, a nomogram model was constructed in this study based on five variables (lymphatic metastasis, international normalized ratio (INR), prothrombin time (PT), tumor differentiation, and number of tumor metastases), which was shown to predict the survival probability of patients with neuroendocrine tumors. Additionally, the proposed nomogram exhibited good ability in predicting survival probability, which may be easily adopted for clinical use.
Light at Night and Risk of Pancreatic Cancer in the NIH-AARP Diet and Health Study
Authors: Xiao Qian , Jones Rena R. , James Peter , Stolzenberg-Solomon Rachael Z.
Published: January 2021

Circadian disruption may play a role in carcinogenesis. Recent research suggests that light at night (LAN), a circadian disruptor, may be a risk factor for cancer. Moreover, LAN has been linked to obesity and diabetes, two risk factors for pancreatic ductal adenocarcinoma (PDAC). Here we examine the relationship between LAN and PDAC in an epidemiologic study of 464,371 participants from the NIH-AARP Diet and Health Study. LAN was estimated from satellite imagery at baseline (1996), and incident primary PDAC cases were ascertained from state cancer registries. Cox proportional hazards models were used to estimate HRs and two-sided 95% confidence intervals (CI) for the association between quintiles of LAN and PDAC in the overall population stratified by sex. Over up to 16.2 years of follow-up, a total of 2,502 incident PDAC were identified in the cohort. Higher estimated LAN exposure was associated with an elevated PDAC risk. Compared with those living in areas in the lowest LAN quintile, those in areas in the highest quintile had a 27% increase PDAC risk [HR (95% CI), 1.24 (1.03–1.49)], with similar risk for men [1.21 (0.96–1.53)] and women [1.28 (0.94–1.75)]. In addition, stronger associations were observed in normal and overweight groups compared with the obese group (Pinteraction = 0.03). Our results support the hypothesis that LAN and circadian disruption may be risk factors for PDAC.

Significance:

Our study suggests that higher LAN is a risk factor for pancreatic cancer, contributing to the growing literature that demonstrates the potentially adverse health effects of light pollution.
Estrogen Receptor β-Mediated Inhibition of Actin-Based Cell Migration Suppresses Metastasis of Inflammatory Breast Cancer
Authors: Thomas Christoforos , Karagounis Ilias V. , Srivastava Ratnesh K. , Vrettos Nicholas , Nikolos Fotis , Francois Noëlle , Huang Menggui , Gong Siliang , Long Qi , Kumar Sushil , Koumenis Constantinos , Krishnamurthy Savitri , Ueno Naoto T. , Chakrabarti Rumela , Maity Amit
Published: January 2021

Inflammatory breast cancer (IBC) is a highly metastatic breast carcinoma with high frequency of estrogen receptor α (ERα) negativity. Here we explored the role of the second ER subtype, ERβ, and report expression in IBC tumors and its correlation with reduced metastasis. Ablation of ERβ in IBC cells promoted cell migration and activated gene networks that control actin reorganization, including G-protein–coupled receptors and downstream effectors that activate Rho GTPases. Analysis of preclinical mouse models of IBC revealed decreased metastasis of IBC tumors when ERβ was expressed or activated by chemical agonists. Our findings support a tumor-suppressive role of ERβ by demonstrating the ability of the receptor to inhibit dissemination of IBC cells and prevent metastasis. On the basis of these findings, we propose ERβ as a potentially novel biomarker and therapeutic target that can inhibit IBC metastasis and reduce its associated mortality.

Significance:

These findings demonstrate the capacity of ERβ to elicit antimetastatic effects in highly aggressive inflammatory breast cancer and propose ERβ and the identified associated genes as potential therapeutic targets in this disease.
Heterogeneity and Clonal Evolution of Acquired PARP Inhibitor Resistance in TP53- and BRCA1-Deficient Cells
Authors: Färkkilä Anniina , Rodríguez Alfredo , Oikkonen Jaana , Gulhan Doga C. , Nguyen Huy , Domínguez Julieta , Ramos Sandra , Mills Caitlin E. , Pérez-Villatoro Fernando , Lazaro Jean-Bernard , Zhou Jia , Clairmont Connor S. , Moreau Lisa A. , Park Peter J. , Sorger Peter K. , Hautaniemi Sampsa , Frias Sara , D'Andrea Alan D.
Published: January 2021

Homologous recombination (HR)-deficient cancers are sensitive to poly-ADP ribose polymerase inhibitors (PARPi), which have shown clinical efficacy in the treatment of high-grade serous cancers (HGSC). However, the majority of patients will relapse, and acquired PARPi resistance is emerging as a pressing clinical problem. Here we generated seven single-cell clones with acquired PARPi resistance derived from a PARPi-sensitive TP53−/− and BRCA1−/− epithelial cell line generated using CRISPR/Cas9. These clones showed diverse resistance mechanisms, and some clones presented with multiple mechanisms of resistance at the same time. Genomic analysis of the clones revealed unique transcriptional and mutational profiles and increased genomic instability in comparison with a PARPi-sensitive cell line. Clonal evolutionary analyses suggested that acquired PARPi resistance arose via clonal selection from an intrinsically unstable and heterogenous cell population in the sensitive cell line, which contained preexisting drug-tolerant cells. Similarly, clonal and spatial heterogeneity in tumor biopsies from a clinical patient with BRCA1-mutant HGSC with acquired PARPi resistance was observed. In an imaging-based drug screening, the clones showed heterogenous responses to targeted therapeutic agents, indicating that not all PARPi-resistant clones can be targeted with just one therapy. Furthermore, PARPi-resistant clones showed mechanism-dependent vulnerabilities to the selected agents, demonstrating that a deeper understanding on the mechanisms of resistance could lead to improved targeting and biomarkers for HGSC with acquired PARPi resistance.

Significance:

This study shows that BRCA1-deficient cells can give rise to multiple genomically and functionally heterogenous PARPi-resistant clones, which are associated with various vulnerabilities that can be targeted in a mechanism-specific manner.
Association of Inflammatory and Insulinemic Potential of Diet and Lifestyle with Risk of Hepatocellular Carcinoma
Authors: Yang Wanshui , Sui Jing , Zhao Longgang , Ma Yanan , Tabung Fred K. , Simon Tracey G. , Lee Dong Hoon , Zeng Xufen , Nguyen Long H. , Meyerhardt Jeffrey A. , Chan Andrew T. , Giovannucci Edward L. , Zhang Xuehong
Published: January 2021

Background:

We prospectively examined the extent to which greater inflammatory and insulinemic potential of diet and lifestyle are associated with the risk of developing hepatocellular carcinoma (HCC) in two nationwide cohorts.

Methods:

Five kinds of pattern scores, including the empirical dietary inflammatory pattern (EDIP), empirical dietary index for hyperinsulinemia (EDIH) and insulin resistance (EDIR), empirical lifestyle pattern score for hyperinsulinemia (ELIH) and insulin resistance (ELIR) were calculated. Multivariable hazard ratios (HR) and 95% confidence intervals (CI) were estimated using Cox regression.

Results:

After an average follow-up of 25.6 years among 119,316 participants, 142 incident HCC cases were documented. Higher adherence to EDIP (HR by comparing extreme tertiles: 2.03; 95% CI, 1.31–3.16; Ptrend = 0.001), EDIH (HR, 1.61; 95% CI, 1.06–2.43; Ptrend = 0.02), and EDIR (HR, 1.62; 95% CI: 1.08–2.42; Ptrend = 0.02) was associated with increased risk of HCC. Likewise, participants with higher scores of ELIH (HR, 1.89; 95% CI, 1.25–2.87; Ptrend = 0.001) and ELIR (HR, 2.05; 95% CI, 1.34–3.14, Ptrend = 0.0004) had higher risk of developing HCC. Additional adjustment for diabetes mellitus and/or body mass index attenuated the magnitude of the associations, indicating that diabetes and/or adiposity may partly mediate the association of these patterns with HCC risk.

Conclusions:

Our findings suggest that inflammation and insulin resistance/hyperinsulinemia are potential mechanisms linking dietary or lifestyle factors and HCC development.

Impact:

Inflammation and insulin resistance/hyperinsulinemia may partly mediate the association of diet and other lifestyles with HCC development, and interventions to reduce the adverse effect of pro-inflammatory and hyperinsulinemic diet and lifestyle may reduce HCC risk.
Detection of Aneuploidy in Cerebrospinal Fluid from Patients with Breast Cancer Can Improve Diagnosis of Leptomeningeal Metastases
Authors: Angus Lindsay , Deger Teoman , Jager Agnes , Martens John W.M. , de Weerd Vanja , van Heuvel Irene , van den Bent Martin J. , Sillevis Smitt Peter A.E. , Kros Johan M. , Bindels Eric M.J. , Heitzer Ellen , Sleijfer Stefan , Jongen Joost L.M. , Wilting Saskia M.
Published: January 2021

Purpose:

Detection of leptomeningeal metastasis is hampered by limited sensitivities of currently used techniques: MRI and cytology of cerebrospinal fluid (CSF). Detection of cell-free tumor DNA in CSF has been proposed as a tumor-specific candidate to detect leptomeningeal metastasis at an earlier stage. The aim of this study was to investigate mutation and aneuploidy status in CSF-derived cell-free DNA (cfDNA) of patients with breast cancer with a clinical suspicion of leptomeningeal metastasis.

Experimental Design:

cfDNA was isolated from stored remnant CSF and analyzed by targeted next-generation sequencing (NGS; n = 30) and the modified fast aneuploidy screening test-sequencing system (mFAST-SeqS; n = 121). The latter method employs selective amplification of long interspaced nuclear elements sequences that are present throughout the genome and allow for fast and cheap detection of aneuploidy. We compared these results with the gold standard to diagnose leptomeningeal metastasis: cytology.

Results:

Leptomeningeal metastasis was cytology proven in 13 of 121 patients. Low DNA yields resulted in insufficient molecular coverage of NGS for the majority of samples (success rate, 8/30). The mFAST-SeqS method, successful in 112 of 121 (93%) samples, detected genome-wide aneuploidy in 24 patients. Ten of these patients had cytology-proven leptomeningeal metastasis; 8 additional patients were either concurrently diagnosed with central nervous system metastases by radiological means or developed these soon after the lumbar puncture. The remaining six cases were suspected of leptomeningeal metastasis, but could not be confirmed by cytology or imaging. Aneuploidy was associated with development of leptomeningeal metastasis and significantly worse overall survival.

Conclusions:

Aneuploidy in CSF-derived cfDNA may provide a promising biomarker to improve timely detection of leptomeningeal metastasis.
Phase I Trial of Encapsulated Rapamycin in Patients with Prostate Cancer Under Active Surveillance to Prevent Progression
Authors: Kemp Bohan Phillip M. , Chick Robert C. , O'Shea Anne E. , Vreeland Timothy J. , Hickerson Annelies T. , Cindass Jessica L. , Ensley Daniel C. , Hale Diane , Clifton Guy T. , Sohn Vance Y. , Thompson Ian M. , Peoples George E. , Liss Michael A.
Published: January 2021

No approved medical therapies prevent progression of low-grade prostate cancer. Rapamycin inhibits cell proliferation and augments immune responses, producing an antitumor effect. Encapsulated rapamycin (eRapa) incorporates rapamycin into a pH-sensitive polymer, ensuring consistent dosing. Here, we present results from a phase I trial evaluating the safety and tolerability of eRapa in patients with prostate cancer. Patients with Gleason ≤7 (3+4) disease (low and intermediate risk) under active surveillance were enrolled in a 3+3 study with three eRapa dosing cohorts (cohort 1, 0.5 mg/week; cohort 2, 1 mg/week; and cohort 3, 0.5 mg/day). Patients were treated for 3 months and followed for an additional 3 months to assess safety, pharmacokinetics, quality of life (QoL), immune response, and disease progression. Fourteen patients (cohort 1, n = 3; cohort 2, n = 3; and cohort 3, n = 8) were enrolled. In cohort 3, one dose-limiting toxicity (DLT; neutropenia) and two non-DLT grade 1–2 adverse events (AE) occurred that resulted in patient withdrawal. All AEs in cohorts 1 and 2 were grade 1. Peak serum rapamycin concentration was 7.1 ng/mL after a 1 mg dose. Stable trough levels (∼2 ng/mL) developed after 48–72 hours. Daily dosing mildly worsened QoL, although QoL recovered after treatment cessation in all categories, except fatigue. Weekly dosing increased naïve T-cell populations. Daily dosing increased central memory cell populations and exhaustion markers. No disease progression was observed. In conclusion, treatment with eRapa was safe and well-tolerated. Daily dosing produced higher frequencies of lower grade toxicities and transient worsening of QoL, while weekly dosing impacted immune response. Future studies will verify clinical benefit and long-term tolerability.

Prevention Relevance: There is an unmet medical need for a well-tolerated treatment capable of delaying progression of newly diagnosed low-grade prostate cancer. This treatment would potentially obviate the need for future surgical intervention and improve the perception of active surveillance as a more acceptable option among this patient population.
Germline Pathogenic Variants in the Ataxia Telangiectasia Mutated (ATM) Gene are Associated with High and Moderate Risks for Multiple Cancers
Authors: Hall Michael J. , Bernhisel Ryan , Hughes Elisha , Larson Katie , Rosenthal Eric T. , Singh Nanda A. , Lancaster Johnathan M. , Kurian Allison W.
Published: January 2021

Pathogenic variants (PVs) in ATM are relatively common, but the scope and magnitude of risk remains uncertain. This study aimed to estimate ATM PV cancer risks independent of family cancer history. This analysis included patients referred for hereditary cancer testing with a multi-gene panel (N = 627,742). Cancer risks for ATM PV carriers (N = 4,607) were adjusted for family history using multivariable logistic regression and reported as ORs with 95% confidence intervals (CIs). Subanalyses of the c.7271T>G missense PV were conducted. Moderate-to-high risks for pancreatic (OR, 4.21; 95% CI, 3.24–5.47), prostate (OR, 2.58; 95% CI, 1.93–3.44), gastric (OR, 2.97; 95% CI, 1.66–5.31), and invasive ductal breast (OR, 2.03; 95% CI, 1.89–2.19) cancers were estimated for ATM PV carriers. Notably, c.7271T>G was associated with higher invasive ductal breast cancer risk (OR, 3.76; 95% CI, 2.76–5.12) than other missense and truncating ATM PVs. Low-to-moderate risks were seen for ductal carcinoma in situ (OR, 1.80; 95% CI, 1.61–2.02), male breast cancer (OR, 1.72; 95% CI, 1.08–2.75), ovarian cancer (OR, 1.57; 95% CI, 1.35–1.83), colorectal cancer (OR, 1.49; 95% CI, 1.24–1.79), and melanoma (OR, 1.46; 95% CI, 1.18–1.81). ATM PVs are associated with multiple cancer risks and, while professional society guidelines support that carriers are eligible for increased breast and pancreatic cancer screening, increased screening for prostate and gastric cancer may also be warranted. c.7271T>G is associated with high risk for breast cancer, with a 3- to 4-fold risk increase that supports consideration of strategies for prevention and/or early detection.

Prevention Relevance:

This study estimated risks for multiple cancers associated with ATM pathogenic variants independent of family history. These results indicate that some common variants may be associated with higher breast cancer risks than previously appreciated and increased screening for prostate and gastric cancer may be warranted for carriers of ATM pathogenic variants.
Neurodevelopmental Outcomes following Prenatal Diagnosis of Isolated Corpus Callosum Agenesis: A Systematic Review
Authors: Bernardes da Cunha Sara , Carneiro Maria Carolina , Miguel Sa Maria , Rodrigues Andrea , Pina Carla
Published: January 2021

Abnormalities of corpus callosum are one of the most common brain anomalies. Fetuses with isolated corpus callosum agenesis (CCA) have a better prognosis than those with additional anomalies. However, unpredictable neurodevelopmental outcomes of truly isolated CCA make prenatal counseling a challenge. The aim of this review is to evaluate neurodevelopmental outcomes in children with prenatal diagnosis of isolated CCA. Controlled clinical trials published between May 23, 2009, and May 23, 2019, using the MeSH term “agenesis of corpus callosum” were reviewed. A total of 942 articles were identified, and 8 studies were included in the systematic review depending on the inclusion criteria. These studies included 217 fetuses with isolated CCA and no other anomalies at prenatal assessment. Neurodevelopmental outcome was reported to be normal in 83 children with a prenatal diagnosis of isolated CCA confirmed at birth within 128 completed assessments. About 45 children presented borderline, moderate, or severe neurodevelopmental outcome. In this review, neurodevelopment was favorable in two-thirds of the cases, but mild disabilities emerged in older children. Despite this, disabilities can occur later beyond school age and a low risk of severe cognitive impairment exists. Our study highlights the essential early diagnosis and proper supportive therapy.
Five-Year Results of a Prospective Multicenter Trial: AdVance XP for Postprostatectomy-Incontinence in Patients with Favorable Prognostic Factors
Authors: Mumm Jan-Niclas , Klehr Benedikt , Rodler Severin , Kretschmer Alexander , Vilsmaier Theresa , Westhofen Thilo , Chaloupka Michael , Schulz Gerald Bastian , Gozzi Christian , Rehder Peter , May Florian , Homberg Roland , Stief Christian G. , Grabbert Markus , Bauer Ricarda M.
Published: January 2021

Objective: The aim of this study was to assess the security, value, and efficacy of the second-generation AdVance male sling XP (Boston Scientific®), after implementation in 2010 with advantageous modifications in the sling structure and needle shape, in a prospective multicenter long-term follow-up study. Methods: In total, 115 patients were included. Exclusion criteria were earlier incontinence (UI) surgery, nocturnal UI, former radiotherapy, or night-time incontinence. We also excluded patients with a functional urethra <1 cm in a preoperatively performed repositioning test. A consistent 24-h pad test, International Quality of Life (IQOL) score, visual analog pain scale (VAS), International Consultation-Incontinence Questionnaire (ICIQ-UI SF), International Index of Erectile Function (IIEF-5), International Prostate Symptom Score (IPSS), and Patient Global Impression of Improvement (PGI-I) scores were requested postoperatively. Results: The 24-month follow-up (114 patients) revealed 64.0% cured and 28.8% improved patients. Mean urine loss was reduced significantly to 19.0 g (p < 0.001). A mean PGI score of 1.5 and a mean VAS score of 0.2 were obtained. The 60-month follow-up (59 patients) revealed 57.6% cured and 25.4% improved patients. Mean urine loss was reduced significantly to 18.3 g (p < 0.001). A mean PGI score of 1.6 and a mean VAS score of 0.2 were obtained. Conclusions: The AdVance XP displays excellent continence results and secure effectiveness over a 5-year period. Moreover, these data are demonstrating low complication rates and improved quality of life in the long-term use of AdVance XP.
Active Surveillance for Incidental (cT1a/b) Prostate Cancer: Long-Term Outcomes of the Prospective Noninterventional HAROW Study
Authors: Herden Jan , Schwarte Andreas , Boedefeld Edith A. , Weissbach Lothar
Published: January 2021

Introduction: Optimal treatment for incidental prostate cancer (IPC) after surgical treatment for benign prostate obstruction is still debatable. We report on long-term outcomes of IPC patients managed with active surveillance (AS) in a German multicenter study. Methods: HAROW (2008–2013) was designed as a noninterventional, prospective, health-service research study for patients with localized prostate cancer (≤cT2), including patients with IPC (cT1a/b). A follow-up examination of all patients treated with AS was carried out. Overall, cancer-specific, and metastasis-free survival and discontinuation rates were determined. Results: Of 210 IPC patients, 68 opted for AS and were available for evaluation. Fifty-four patients had cT1a category and 14 cT1b category. Median follow-up was 7.7 years (IQR: 5.7–9.1). Eight patients died of which 6 were still under AS or watchful waiting (WW). No PCa-specific death could be observed. One patient developed metastasis. Twenty-three patients (33.8%) discontinued AS changing to invasive treatment: 12 chose radical prostatectomy, 7 radiotherapy, and 4 hormonal treatment. Another 19 patients switched to WW. The Kaplan-Meier estimated 10-year overall, cancer-specific, metastasis-free, and intervention-free survival was 83.8% (95% CI: 72.2–95.3), 100%, 98.4% (95% CI: 95.3–99.9), and 61.0% (95% CI: 47.7–74.3), respectively. In multivariable analysis, age (RR: 0.97; p < 0.001), PSA density ≥0.2 ng/mL2 (RR: 13.23; p < 0.001), and PSA ≥1.0 ng/mL after surgery (RR: 5.19; p = 0.016) were significantly predictive for receiving an invasive treatment. Conclusion: In comparison with other AS series with a general low-risk prostate cancer population, our study confirmed the promising survival outcomes for IPC patients, whereas discontinuation rates seem to be lower for IPC. Thus, IPC patients at low risk of progression may be good candidates for AS.
A Fundação de Apoio e Mobilização Social (FAMFS), o esporte e a inclusão social
Authors: Rossi Junior Renildo , Pereira Antonino , Alencar Roselene de , Rossi Mariana Santiago , Azevêdo Paulo Henrique
Published: January 2021

O entendimento de que o esporte favorece a inclusão social, pode ser visto em um grande número de projetos esportivos. Apesar disso, este constitui um fenômeno multifacetado e complexo, que carece de ser compreendido na sua contribuição real ou potencial para os processos de desenvolvimento da humanidade. Ante ao exposto, a presente investigação objetivou analisar e discutir os contributos da Fundação de Apoio ao Cidadão e Mobilização Social (FAMFS), para a inclusão social no município de Feira de Santana, Estado da Bahia – Brasil, com ações relacionadas do esporte. O presente artigo justifica-se, ante a necessidade de estudos de impacto de projetos sociais nas comunidades, a partir da implementação de atividades esportivas. Para tanto, recorremos ao método qualitativo, de base etnográfica. As fontes de coleta de dados utilizadas foram entrevistas, documentos (base institucional, impressa e eletrônica), e notas de campo provenientes das atividades de observação-participante. A maioria dos resultados aponta que o projeto mais evidenciado envolveu a fabricação de materiais esportivos,através dos Programas “Pintando a Liberdade e Cidadania”, beneficiando as crianças, os adolescentes, mas também as suas famílias. O principal parceiro da FAMFS, na dinamização dos vários projetos esportivos sociais foi o poder público. As estratégias utilizadas pela fundação para cooperação e diálogo intersetorial na dinamização dos seus projetos esportivos sociais, envolveu a formalização de convênios com o poderpúblico, nos três níveis (municipal, estadual e federal). Em síntese, os dados evidenciam que as ações da FAMFS beneficiaram a inclusão social de crianças e adolescentes, e as suas famílias, com ações relacionadas ao esporte. Esta intervenção foi amplamente reconhecida e valorizada pelas autoridades públicas brasileiras e por diversas instituições nacionais e internacionais.
Slow Cities: uma experiência da contemporaneidade
Authors: Oliveira Eloisa Estrela de
Published: January 2021

Na modernidade o capitalismo é a ordem social em ascensão, o capital surge para desterritorializar e mudar a relação das pessoas e instituições com o tempo, com suas identidades e com o território. Num mundo globalizado, cidades caminham para homogeneização. “Fluidez”, velocidade e instabilidade (traços de uma sociedade líquida moderna) fazem surgir movimentos sociais contrários a esta lógica e que passam a questionar seus efeitos sobre os indivíduos, mostrando que existe alternativa para uma vida mais equilibrada e saudável, o slow movement é um deles e dentre suas vertentes, o movimento slow cities surge e traz para a reflexão a necessidade de repensar a vida nas cidades contemporâneas e a necessidade de humanização e de resgate das identidades nestes espaços.
Aspectos epidemiológicos e gastos em saúde por demências no Brasil
Authors: Zalli Marcelo , Farah Henrique Orefice , Antunes Mateus Dias
Published: January 2021

O envelhecimento em nosso país ocorre de forma progressiva. A demência é uma síndrome que se caracteriza pelo declínio cognitivo. O objetivo do estudo foi traçar os aspectos epidemiológicos e descrever os gastos em saúde por demências no Brasil. Trata-se de um estudo transversal, descritivo de abordagem quantitativa que utilizou dados sobre demência em 2018 a partir de fonte secundária do Ministério da Saúde. Os dados coletados foram sexo, idade, registros do número de autorização de internação hospitalar, valores por internamento, dias de internação, número de óbitos e taxa de mortalidade. Os dados foram tabulados no Microsoft Excel 2010 e apresentados por meio da estatística descritiva. Ocorreram 8.663 internações hospitalares por demências no Brasil, no âmbito do Sistema Único de Saúde. A maioria era do sexo masculino, 52,4%. A soma dos valores pagos por atendimentos de todas essas internações hospitalares foi de R$ 14.762.523,68 e o valor gasto por serviço hospitalar total foi de R$ 13.619.466,40. Quanto aos óbitos devidos à demência no Brasil, foi de 275 e a taxa de mortalidade foi de 9,51. Os valores de internação descritos no estudo refletem o montante elevado financeiro disposto para síndromes demenciais, tanto em internações, quanto em gastos com atendimentos. Os valores apesar de expressivos refletem parcialmente a realidade, uma vez que nem todos os casos são notificados pelos profissionais e instituições. Fica assim evidente a necessidade de incentivos à programas públicos com referência à síndrome demencial, objetivando o diagnóstico adequado, tratamento e cuidados e a busca por redução de custos.
Concepts of indirect calorimetry on metabolic disorders: a narrative review
Authors: San Martin Rocio , Brandao Camila Fernanda Cunha , Junqueira-Franco Marcia Varella Morandi , Junqueira Gizela Pedroso , Chueire Fernando Bahdur , Oliveira Joyce Cristina Santos de , Cunha Selma Freire Carvalho da , Suen Vivian Marques Miguel , Marchini Julio Sergio
Published: January 2021

Introduction: Indirect calorimetry remains a gold standard in measuring resting energy expenditure in the clinical field. Through its measurements, it is possible to offers a patient’s energy needs to maximize nutritional therapy benefits. However, the concepts and methodological basis of collected data can be difficult to be interpreted by users in clinical practice. Objective: To address the concepts of total daily energy expenditure and its components and present the methodological aspects of indirect calorimetry that can guide the clinical field. Method: Narrative bibliographic review using the electronic Pubmed (US National Library of Medicine), SCOPUS, and Scientific Electronic Library Online (SCIELO) databases. The research was carried out in the period between 1905-2019, using the following identifiers in Health Sciences Descriptors: Basal Metabolism, Energy Metabolism and Indirect Calorimetry. We selected 55 researches published that presented contents related to the objectives of this study. Result: The total daily energy expenditure (TDEE) is comprised of three main components, such as physical activity (PA), thermic effect of food (TEF) and basal metabolic rate (BMR) and/or resting energy expenditure (REE). The REE is generally evaluated by indirect calorimetry, which also provides information on the respiratory coefficient (RQ) or oxidation of substrates. Its result varies depending on the existence of some metabolic disorders such as obesity or malnutrition. Therefore, the proper management of the methodological aspects of indirect calorimetry and its subsequent interpretation in metabolic disorders is essential to guarantee the results’ quality. Conclusion: Energy expenditure concepts and the methodological basis of indirect calorimetry are relevant to providing individualized attention to patients with metabolic disorders. This review can be used as a practical guide, helping to understand the correct application of the indirect calorimetry technique in studies related to energy expenditure with an emphasis on metabolic disorders.
Ética das virtudes: em busca da excelência
Authors: Cruz Jorge Silva
Published: January 2021

A teoria ética das virtudes é o modelo mais antigo de filosofia moral, mas a partir do Renascimento foi relegada para segundo plano com o surgimento da ética kantiana do dever e do consequencialismo de Bentham e Mill. No âmbito da saúde, as teorias éticas centradas na virtude e no caráter continuaram a ser preponderantes até aos anos 70 do século passado, quando surgiu a bioética como uma nova área do saber, que procura refletir sobre as implicações éticas resultantes dos progressos científicos e tecnológicos na vida humana e animal, e no ambiente. Assistiu-se a uma mudança de paradigma na ética dos cuidados de saúde, de um modelo baseado na virtude e na inviolabilidade da vida humana, expresso no Juramento de Hipócrates, para um modelo cimentado na autonomia e qualidade de vida do paciente, para o que contribuiu a proposta da metodologia principialista de Beauchamp e Childress e da crescente influência do utilitarismo nas comissões de ética. Nos últimos anos, tem havido um interesse renovado pelas teorias éticas da virtude devido ao contributo de pensadores como Elizabeth Anscombe, Alasdair MacIntyre e Edmund D. Pellegrino. Foi realizada uma revisão sobre a teoria ética das virtudes a partir das obras de Edmund D. Pellegrino e David C. Thomasma, pioneiros da bioética e dos principais promotores da ética das virtudes na prática clínica, bem como após pesquisa do tema nas bases de dados NCBI/PubMed (National Center for Biotechnology Information) e SciELO (Scientific Eletronic Library Online). Após uma apresentação da história do conceito filosófico de virtude e dos aspetos mais representativos da teoria ética das virtudes, são destacadas oito virtudes particularmente relevantes para a atividade clínica: a fidelidade à promessa, a compaixão, a prudência, a justiça, a coragem, a moderação, a integridade e o altruísmo. Estas e outras virtudes são, em nossa opinião, essenciais para uma prática médica mais humanizada que tenha em conta o bem do paciente, e contribuirão também para contrabalançar a hegemonia do principialismo e de teorias éticas que desvalorizem o papel central do agente no debate bioético atual.
Turismo indígena, protagonismo e desenvolvimento local
Authors: Rosa Patricia Carvalho , Rosa Lana Mignone Viana , Nassar Pedro Meloni
Published: January 2021

Este artigo apresenta a experiência da elaboração do primeiro Plano de Visitação proposto na região do Médio Solimões, Amazonas, conduzido pelos moradores da Terra Indígena Jaquiri, sobreposta à Reserva Estadual de Desenvolvimento Sustentável Mamirauá. Buscou-se por objetivo discutir o Plano de Visitação como estratégia para o fortalecimento do turismo de base comunitária, desta forma, apresenta-se o interesse da aldeia em desenvolver através dele ações que valorizem e criem meios de visibilidade política e cultural ao coletivo indígena Kambeba, assim como uma alternativa sustentável de renda, operando concomitantemente como instrumento de fortalecimento, gestão e proteção de seu território.
Hospitalidade e enoturismo em Andradas (MG)
Authors: Silva Michele Cristina da Costa , Gimenes-Minasse Maria Henriqueta Sperandio Garcia
Published: January 2021

O enoturismo é uma modalidade do Turismo Gastronômico e consiste no deslocamento de pessoas motivadas pela degustação e elaboração de vinhos, bem como pela apreciação das tradições, da gastronomia, das paisagens naturais e das tipicidades das regiões produtoras. No Brasil os destinos enoturísticos mais consagrados se encontram no Rio Grande do Sul, embora iniciativas em outras localidades brasileiras estejam ganhando destaque no mercado nacional. Dentre estes novos destinos encontra-se Andradas (MG), que possui atualmente seis vinícolas abertas para visitação. Destas, por conta do volume de bebida produzida e pelos prêmios obtidos em premiações nacionais e internacionais, destaca-se a Vinícola Casa Geraldo. Este artigo objetiva analisar as atividades de visitação oferecidas pela Vinícola Casa Geraldo a partir dos conceitos de hospitalidade, acolhimento e comensalidade. Trata-se uma pesquisa de caráter qualitativo desenvolvida a partir de revisão bibliográfica, observação direta não participante e entrevista semiestruturada com o gestor da Vinícola em questão. Dentre os principais resultados, aponta-se: oferece boa estrutura e atendimento atencioso e amigável dos visitantes, incorporando aspectos de hospitalidade e acolhimento sem que haja um planejamento específico para isto; a comensalidade se materializa a partir das degustações que ocorrem em diferentes momentos da visitação e por meio dos serviços de seu restaurante; a hospitabilidade é priorizada em relação aos conhecimentos técnicos na contratação dos atendentes. Considerando a opções de visitação ofertadas, a Vinícola pertence à categoria “diferenciado” de programas de visitação (Castro et al., 2017) e parece estar orientada a atender turistas das categorias “interessado em vinho” e “novato no vinho” (Charters & Ali-Knight, 2002).