bluuebunny/crossref_metadata_2025 huggingface dataset:
How Cancer Risk SNPs May Contribute to Prostate Cancer Disparities
Authors: Mavura Mnaya Y. , Huang Franklin W.
Published: July 2021

Disparities in cancer incidence, prevalence, burden, and outcome exist among specific population groups in the United States. Researchers have identified germline genetic risk single-nucleotide polymorphisms (SNP) that differ by ancestry and may contribute to some of these differences. In this issue of Cancer Research, Han and colleagues found the prostate cancer risk SNP rs4713266 is associated with increased risk of patients with African ancestry. The authors investigated the functional role of the risk SNP, finding that it alters activity of a NEDD9 enhancer and increases NEDD9 expression. The study provides epidemiologic and mechanistic insight into factors that may drive prostate cancer disparities.

See related article by Han et al., p. 3766
Deletion of 16q22.2q23.3 in a Boy with a Phenotype Reminiscent of Silver-Russell Syndrome
Authors: Lengyel Anna , Pinti Éva , Eggermann Thomas , Fekete György , Haltrich Irén
Published: July 2021

A 15-month-old boy presented with growth and global developmental delay, feeding difficulties, sleep disturbance and several minor anomalies, including a large anterior fontanel, relative macrocephaly, and a triangular face. Clinical suspicion prompted genetic investigations for Silver-Russell syndrome and related disorders. SNP array analysis led to the diagnosis of an approximately 10-Mb large deletion of the long arm in chromosome 16q22.2q23.3. Interstitial deletions of 16q show a wide variability of related features; however, considering the differences in size and location of the deletions in the known patients, the phenotypic overlap is surprising. Here, we report a novel microdeletion, compare the proband with data from scientific literature and international databases, and discuss possible diagnostic implications.
Primary Cranial Vault Lymphoma Extending between Subcutaneous Tissue and Brain Parenchyma without Skull Destruction after Mild Head Trauma: A Case Report and Literature Review
Authors: Setta Kengo , Beppu Takaaki , Sato Yuichi , Saura Hiroaki , Nomura Junichi , Sugai Tamotsu , Ogasawara Kuniaki
Published: July 2021

Malignant lymphoma of the head rarely arises outside of the brain parenchyma as primary cranial vault lymphoma (PCVL). A case of PCVL that invaded from subcutaneous tissue into the brain, passing through the skull, and occurred after mild head trauma is reported along with a review of the literature. The patient was a 75-year-old man with decreased activity. One month before his visit to our hospital, he bruised the left frontal area of his head. Magnetic resonance imaging showed homogeneously enhanced tumors with contrast media in the subcutaneous tissue corresponding to the head impact area and the cerebral parenchyma, but no obvious abnormal findings in the skull. A biopsy with craniotomy was performed under general anesthesia. The pathological diagnosis was diffuse large B-cell lymphoma. On histological examination, tumor cells grew aggressively under the skin. Tumor cells invaded along the emissary vein into the external table without remarkable bone destruction and extended across the skull through the Haversian canals in the diploe. Tumor cells were found only at the perivascular areas in the dura mater and extended into the brain parenchyma. Considering the history of head trauma and the neuroimaging and histological findings, the PCVL in the present case arose primarily under the skin, passed though the skull and dura mater, and invaded along vessels and reached the brain.
Hepatic Arterial Infusion Chemotherapy Is a Feasible Treatment Option for Hepatocellular Carcinoma: A New Update
Authors: Hendi Maher , Mou Yiping , Lv Jiemin , Zhang Bin , Cai Xiujun
Published: July 2021

Background: Hepatic arterial infusion chemotherapy (HAIC) is one option for treating massive tumors and unresectable hepatocellular carcinoma (HCC). However, there is a lack of remedial treatment after these treatments are ineffective or failed. Summary: Some studies have discovered that HAIC has greater survival in patients with advanced HCC. A previous study has shown that HAIC is effective in the treatment of advanced HCC, and the data on randomized clinical trials are limited and unclear. Key Message: More clinical trials and research are needed in order to make HAIC a standard and recommended therapy for advanced HCC. Our review focuses on the clinical applications of hepatic artery infusion treatment.
Safety and Efficacy of Ibutilide for Acute Pharmacological Cardioversion of Rheumatic Atrial Fibrillation
Authors: Shenthar Jayaprakash , Banavalikar Bharatraj , Valappil Sanjai Pattu , Deshpande Saurabh , Nireshwalia Aparna , Padmanabhan Deepak , Reddy Sathish S.
Published: July 2021

Introduction: Ibutilide is indicated for acute cardioversion of nonvalvular atrial fibrillation (AF). However, its efficacy and safety in the pharmacological cardioversion of rheumatic AF are unknown. Methods: Patients with mild-to-moderate rheumatic mitral valve (MV) disease with symptomatic, paroxysmal, or persistent AF were included in the analysis. Intravenous ibutilide was administered at doses tailored to body weight (0.5–2.0 mg) for over 10 min. The primary end point was efficacy, assessed as the rate of conversion of AF to sinus rhythm. The secondary end point was safety, including arrhythmic events and death within 24 h of drug initiation. Results: From June 2016 to October 2018, 165 patients (94 with mitral stenosis, 23 with mitral regurgitation, 11 with mixed MV disease, and 37 with MV replacement) received ibutilide (mean dose 0.90 ± 0.54 mg). Ibutilide successfully converted AF to sinus rhythm in 127/165 (76.9%) patients, with a conversion time of 7.9 ± 4.1 min. The QTc increased from 419.9 ± 15.8 to 487.5 ± 34 ms after ibutilide administration (p < 0.001). The mean change in QTc after ibutilide administration (∆QTc) was 72.01 ± 36.03. There were no deaths, but 3 patients (1.8%) developed torsades de pointes (TdP) requiring defibrillation 55 ± 37 min after infusion. Conclusion: Ibutilide cardioverted 77% of rheumatic AF to sinus rhythm, indicating its potential as a clinically useful option for pharmacological cardioversion of rheumatic AF. TdP is a potentially serious adverse event that requires careful monitoring.
Rhamnazin Ameliorates Traumatic Brain Injury in Mice via Reduction in Apoptosis, Oxidative Stress, and Inflammation
Authors: Yang Boxiao , Zhang Rui , Sa Qire , Du Yanli
Published: July 2021

Background: Traumatic brain injury (TBI) is posing serious health challenges for people across the globe due to high morbidity and mortality. However, none of the agents prevents or limits the damage caused by TBI because of its multifactorial etiology. Thus, the discovery of novel agents which can act via several pathways could serve the purpose and afford favorable consequence against TBI. Therefore, in the present article, we intended to investigate the protective effect of rhamnazin (RMZ), a dimethoxyflavone against experimentally induced TBI in mice. Methods: The effect of RMZ was investigated on cerebral edema and grip test score after induction of experimental brain injury in rats. The effect of RMZ was also investigated on neuronal degeneration in brain tissues of the experimental mice via Nissl staining and flow cytometry analysis. The expression of Bax and Bcl-2 was also quantified using Western blot analysis. The level of inflammatory cytokines (TNF-α and IL-1β) and oxidative stress markers (malondialdehyde, superoxide dismutase, and glutathione peroxidase) was also determined using enzyme-linked immunosorbent assay. Results: RMZ showed a significant reduction in edema and improved grip strength. It also prevented neuronal degeneration via inhibition of neuronal apoptosis as shown by flow cytometry analysis. RMZ showed an antiapoptotic effect via reduction of Bax and increased the expression of Bcl-2 in Western blot analysis. It also showed to inhibit oxidative stress and inflammation compared to the TBI group. Conclusion: Collectively, our study is first to demonstrate the protective effect of RMZ against experimentally induced TBI in rats.
Pressurized Intraperitoneal Aerosol Chemotherapy-Related Clinical Trials in the Treatment of Peritoneal Metastases
Authors: Ukegjini Kristjan , Putora Paul Martin , Guidi Marisa , Süveg Krisztian , Cihoric Nikola , Widmann Bernhard , Steffen Thomas
Published: July 2021

Introduction: Pressurized intraperitoneal aerosol chemotherapy (PIPAC) is a treatment option for patients with peritoneal metastases. We evaluated the current status of ongoing prospective clinical trials investigating PIPAC to provide an overview and predict trends in this field. Methods: All 367,494 records of clinical trials registered at ClinicalTrials.gov were searched for trials dealing with PIPAC. Active or unpublished trials were further analyzed. Results: In total, 22 clinical trials were identified and selected for further analyses. Most trials had a single-arm design and were phase I or II. No phase III trials were registered. Academic centers were recorded as primary sponsors in the majority of trials (63.6%). Every year, between 2 and 5 new trials were initiated. In 17 trials (81.8%), PIPAC was used in a palliative setting only, 2 trials performed PIPAC in a neoadjuvant setting, and 2 trials performed PIPAC in an adjuvant setting. Six different drugs (doxorubicin, cisplatin, oxaliplatin, nab-paclitaxel, 5-fluorouracil, and docetaxel) were used in these clinical trials. Most trials investigated the efficacy (n = 15) or safety (n = 7) of PIPAC therapies. Conclusions: The results of ongoing clinical trials will bring specific information on indications for PIPAC as well as the impact of PIPAC on quality of life and overall survival.
Google Trends Data: A Potential New Tool for Monitoring the Opioid Crisis
Authors: Ghosh Abhishek , Bisaga Adam , Kaur Simranjit , Mahintamani Tathagata
Published: July 2021

Introduction: There is a need to strengthen the standard surveillance of the opioid overdose crisis in the USA. The role of Google Trends (GT) was explored in this context. Methods: In this study, a systemic GT search was done for a period from January 2004 to December 2018. “Naloxone” and “drug overdose” were chosen as search inputs. By using locally weighted scatterplot smoothing, we locally regressed and smoothed the relative search data generated by the GT search. We conducted a changepoint analysis (CPA) to detect significant statistical changes in the “naloxone” trend from 2004 to 2018. Cross-correlation function analyses were done to examine the correlation between 2 time series: year-wise relative search volume (RSV) for “naloxone” and “drug overdose” with the age-adjusted drug overdose mortality rate. Pearson’s correlation was performed for the state-wise age-adjusted mortality rate due to drug overdose and RSV for “naloxone” and “drug overdose.” Results: Smoothed and regressed GT of “naloxone” were similar to the “opioid overdose” trend published by the National Center for Health Statistics. The CPA showed 2 statistically significant points in 2011 and 2015. CPA of year-wise RSV for “naloxone” and “drug overdose” showed significantly positive correlation with the age-adjusted drug overdose mortality at lag zero. State-wise RSV for “naloxone” and “drug overdose” too showed a strong and significant positive correlation with the state-wise mortality data. Discussion/Conclusion: Inexpensive, publicly accessible, real-time GT data could supplement and strengthen the monitoring of opioid overdose epidemic if used in conjunction with the existing official data sources.
The Early Diagnostic and Prognostic Value of BIRC5 in Clear-Cell Renal Cell Carcinoma Based on the Cancer Genome Atlas Data
Authors: Wang Jingyuan , Chen Min , Dang Chengxue , Zhang Hao , Wang Xin , Yin Jianhao , Jia Rui , Zhang Yong
Published: July 2021

Purpose: The aim of this study was to investigate the role of BIRC5 for early diagnosis and prognosis in clear-cell renal cell carcinoma (ccRCC) by studying the expression of BIRC5 and the correlation between BIRC5 expression and clinicopathological parameters and prognosis in ccRCC. Methods: The BIRC5 expression in ccRCC tissues and normal kidney tissues was measured using the Cancer Genome Atlas database and the Human Protein Atlas database. The correlation between BIRC5 expression and clinicopathological parameters and prognosis in ccRCC was analyzed using UALCAN, the Kaplan-Meier plotter, GEPIA, and SurvExpress. Thirteen-paired ccRCC plasma samples were used to verify the BIRC5 early diagnosis value of ccRCC. Results: The BIRC5 expression is significantly higher in ccRCC than in normal kidney tissues, and is correlated with the clinical stage and pathological grade of ccRCC (p < 0.05). The result of analyzing the relationship between BIRC5 expression and outcomes in ccRCC indicates that a high BIRC5 expression is an independent prognostic factor affecting the overall survival and disease-free survival of ccRCC (p < 0.05). Compared with normal kidney tissues, the immunohistochemical test shows that BIRC5 is significantly upregulated in ccRCC tissues. mRNA expression levels of BIRC5 were significantly higher in the ccRCC plasma than normal (p < 0.05). Conclusions: The high expression of BIRC5 is an important indicator for the prognosis of ccRCC, which makes BIRC5 an effective biomarker for predicting the prognosis of patients in ccRCC. BIRC5 may be a great potential biomarker for early diagnosis of ccRCC.
Long-Term Risk of Ischemic Stroke among Elderly Survivors of Non-Traumatic Subarachnoid Hemorrhage
Authors: Parasram Melvin , Parikh Neal S. , Merkler Alexander E. , Ch’ang Judy H. , . Navi Babak B , Kamel Hooman , Zhang Cenai , Murthy Santosh B.
Published: July 2021

Introduction: Non-traumatic subarachnoid hemorrhage (SAH) is associated with poor long-term functional outcomes, but the risk of ischemic stroke among SAH survivors is poorly understood. Objectives: The aim of this study was to evaluate the risk of ischemic stroke among survivors of SAH. Methods: We performed a retrospective cohort study using claims data from Medicare beneficiaries from 2008 to 2015. The exposure was a diagnosis of SAH, while the outcome was an acute ischemic stroke, both identified using previously validated ICD-9-CM diagnosis codes. We used Cox regression analysis adjusting for demographics and stroke risk factors to evaluate the association between SAH and long-term risk of ischemic stroke. Results: Among 1.7 million Medicare beneficiaries, 912 were hospitalized with non-traumatic SAH. During a median follow-up of 5.2 years (IQR, 2.7–6.7), the cumulative incidence of ischemic stroke was 22 per 1,000 patients per year among patients with SAH, and 7 per 1,000 patients per year in those without SAH. In adjusted Cox models, SAH was associated with an increased risk of ischemic stroke (HR, 2.0; 95% confidence interval, 1.4–2.8) as compared to beneficiaries without SAH. Similar results were obtained in sensitivity analyses, when treating death as a competing risk (sub HR, 3.0; 95% CI, 2.8–3.3) and after excluding ischemic stroke within 30 days of SAH discharge (HR, 1.5; 95% CI, 1.1–2.3). Conclusions: In a large, heterogeneous national cohort of elderly patients, survivors of SAH had double the long-term risk of ischemic stroke. SAH survivors should be closely monitored and risk stratified for ischemic stroke.
Transporters, TBC1D4, and ARID5B Variants to Explain Glycated Hemoglobin Variability in Patients with Type 2 Diabetes
Authors: Gonzalez-Covarrubias Vanessa , Sánchez-Ibarra Héctor , Lozano-Gonzalez Karla , Villicaña Sergio , Texis Tomas , Rodríguez-Dorantes Mauricio , Cortés-Ramírez Sergio , Lavalle-Gonzalez Fernando , Soberón Xavier , Barrera-Saldaña Hugo
Published: July 2021

Introduction: Genetic variants could aid in predicting antidiabetic drug response by associating them with markers of glucose control, such as glycated hemoglobin (HbA1c). However, pharmacogenetic implementation for antidiabetics is still under development, as the list of actionable markers is being populated and validated. This study explores potential associations between genetic variants and plasma levels of HbA1c in 100 patients under treatment with metformin. Methods: HbA1c was measured in a clinical chemistry analyzer (Roche), genotyping was performed in an Illumina-GSA array and data were analyzed using PLINK. Association and prediction models were developed using R and a 10-fold cross-validation approach. Results: We identified genetic variants on SLC47A1, SLC28A1, ABCG2, TBC1D4, and ARID5B that can explain up to 55% of the interindividual variability of HbA1c plasma levels in diabetic patients under treatment. Variants on SLC47A1, SLC28A1, and ABCG2 likely impact the pharmacokinetics (PK) of metformin, while the role of the two latter can be related to insulin resistance and regulation of adipogenesis. Conclusions: Our results confirm previous genetic associations and point to previously unassociated gene variants for metformin PK and glucose control.
Evaluation of Emergency Health-Care Initiatives to Reduce Overcrowding in a Referral Medical Complex, Jeddah, Saudi Arabia
Authors: Alabbasi Khalid , Kruger Estie , Tennant Marc
Published: July 2021

Purpose: Excessive delays and emergency department (ED) overcrowding have become an increasingly major problem for public health worldwide. This study was to assess the key strategies adopted by an ED, at a public hospital in Jeddah, to reduce delays and streamline patient flow. Materials and Methods: This study was a service evaluation for a Saudi patient population of all age-groups who attended the ED of a public hospital for the period between June 2016 and July 2019. The Saudi initiative to reduce the ED visits at the King Abdullah Medical Complex hospital has started on August 7, 2018. The initiative was to apply an urgency transfer policy which outlines the procedures to follow when patients arrive to the ED where they are reviewed based on the Canadian Triage and Acuity Scale (CTAS). Patients with less-urgent conditions (category 4 and 5) are referred to a primary health-care practice (where a family medicine consultant is available). Patients with urgent conditions (category 1–3) are referred to a specialized health-care centre if the service is not currently provided. To test the effectiveness of ED initiative on reducing the overcrowd, data were categorized into before and after the initiative. The bivariate analysis χ2 tests and 2 sample t-tests were run to explore the relationship of gender and age with dependent variable emergency. Results: A total of 233,998 patients were included in this study, 61.8% of them were males and the average age of ED patients were 35.5 ± 18.6 years. The majority of cases were those classified as “less urgent” (CTAS 4), which accounted for 65.4%. Number of ED visits before and after the initiative was 67 and 33%, respectively. ED waiting times after the initiative have statistically significantly decreased across all acuity levels compared to ED waiting times before the initiative. Conclusion and Implication: The findings suggest that the majority of patients arrive to the ED with less-urgent conditions and arrived by walking-in. The number of cases attending the ED significantly decreased following the introduction of the urgency transfer policy. Referral for less-urgent patients to primary health-care centre may be an important front-end operational strategy to relieve congestion.
Diagnostic Accuracy of Trichoscopy in Inflammatory Scalp Diseases: A Systematic Review
Authors: Golińska Joanna , Sar-Pomian Marta , Rudnicka Lidia
Published: July 2021

Background: The common inflammatory scalp diseases, such as psoriasis, seborrheic dermatitis, lichen planopilaris, discoid lupus erythematosus, contact dermatitis, or pemphigus may share similar clinical features. Objective: To identify and systematically review the available evidence on the accuracy of trichoscopy in inflammatory scalp disorders. Methods: A systematic review was performed according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A total of 58 articles were included in the analysis. Results: The following trichoscopy features were found to show the highest specificity for the respective diseases: in psoriasis: diffuse scaling, simple and twisted red loops, red dots and globules, and glomerular vessels; in seborrheic dermatitis: atypical vessels, thin arborizing vessels, and structureless red areas; in discoid lupus erythematosus: follicular plugs and erythema encircling follicles; in lichen planopilaris: milky red areas or fibrotic patches; in contact dermatitis: twisted red loops; in pemphigus foliaceus: white polygonal structures and serpentine vessels; in pemphigus vulgaris: red dots with whitish halo and lace-like vessels; and in dermatomyositis: lake-like vascular structures. Limitations: Different nomenclature and variability in parameters, which were analyzed in different studies. Conclusion: This systemic analysis indicates that trichoscopy may be used with high accuracy in the differential diagnosis of inflammatory scalp diseases.
Influence of Breast Reduction Surgery on Long-Term Breast Cancer Risk in Austria
Authors: Niepel Albert , Schwake Sven , Zeichmann Mira , Noltze Ariel , König Viktoria , Sokullu Fuat , Schenk Clara , Pallikunnel Shanon , Hellekes Dirk , Koller Rupert , Steinkellner Lara
Published: July 2021

Introduction: Breast reduction surgery is one of the most frequently performed surgeries amongst plastic and reconstructive surgeons worldwide. Previous studies have shown decreased risk of breast cancer development in women undergoing breast reduction surgery of up to 28%. We aimed to evaluate the relative risk of breast cancer development in our patients after breast reduction surgery in relation to the general female population of Austria. Methods: A total of 637 women underwent breast reduction surgery between 2003 and 2017 at our department. From those women, 513 patients completed a follow-up assessment of breast cancer development and were included into the study sample. The age-specific incidence rate data of the general female population of Austria served as the control group and basis for the calculation of the standardized incidence ratio (SIR) and Poisson test. Results: Relative to 5.66 expected cases of breast cancer, our cohort showed 1 subject with breast cancer after breast reduction surgery (SIR = 0.1765). An exact Poisson test was carried out to determine the level of significance of the difference between the incidence rate observed in the sample compared to the expected rate based on the age-specific incidence rates of the general population (p = 0.023, α = 0.05). Discussion: Our study underlines the strong evidence of previous studies for significant breast cancer reduction in patients after reductive mammoplasty. In comparison to the general female population of Austria, our cohort showed a reduction in breast cancer incidence of about 82%. The authors believe that different techniques in reduction mammoplasty have different levels of safety regarding the prevention and risk reduction for breast cancer. Further investigation must be conducted to evaluate the reduction of breast cancer risk with different surgical techniques.
Building Change Detection in Myanmar using Image Processing
Authors: Win Ei Phyu Sin
Published: July 2021

Building change detection makes it is easy to locate buildings from a distance in the sky. They can also observe the development of rural, or urban areas between 10 decade and present. So, higher resolution satellite and aerial pictures are needed to detect buildings. Building shape varies from one to another over the world. Rural areas are sparsely populated, but densely and complexly populated in urban areas. And it is difficult to detect separate buildings from them. To solve obstacles, non-linear filter, line extracting and region thresholding method is used in this research. The test images from the last decade and images of current year are acquired by using google earth pro, and have different spatial resolutions. Detection area is Hlaingthaya Township, Yangon, Myanmar. This system is simulated with MATLAB programming language
Case Study on Road Accidents in a Motorcycle-Propelled Public Transport
Authors: Maming Jimmy Bernabe , Imbong Maria Fe Planco
Published: July 2021

The Philippines utilizes the motorcycle as informal transport services. Thus, the birth of the “habal-habal” motorcycle taxi that traverses not only in the secondary roads but also in the national highways. This case study intends to describe the experiences of the participants on the list of occurrences that ended in casualty and fatality and to identify problems in the policy implementations pertinent to road safety and management. This study utilizes interviews, observation, and data reviews in gathering the data while the Mayring (2002) approach was used in the data analysis procedure. Themes come out from the narratives of the participants like unlicensed driving involving minors, under-reporting of fatalities and non-use of safety gear during the flight. The output of the study is a proposed new Model on Malay Transportation Development and Management.
Atividade antifúngica de isolados clínicos de Candida não-albicans aos óleos essenciais de Syzygium aromaticum (cravo-da-índia) e Eucalyptus globulus (eucalipto-comum)
Authors: Santos Júnior Claudio José dos , Rodrigues Dálity Keffelen de Barros , Dantas Rita Dâmaris Soares , Souza Aryanna Kelly Pinheiro
Published: July 2021

Introdução: O gênero Candida infecta o ser humano com alta incidência, sendo a espécie Candida albicans a mais isolada em infecções invasivas e superficiais. Porém, tem sido relatado um aumento considerável de espécies de Candida não-albicans em infecções fúngicas. Os óleos essenciais, por serem voláteis, podem agir como sinais de comunicação química e arma de defesa. Objetivo: Avaliar a eficácia, in vitro, dos óleos essenciais de Syzygium aromaticum e Eucalyptus globulus na inibição do crescimento de espécies de Candida não-albicans. Métodos: Para avaliação da atividade antifúngica de S. aromaticum e de E. globulus e do efeito dos seus óleos essenciais sobre a micromorfologia das espécies Candida krusei, Candida parapsilosis e Candida glabrata, foram empregadas, nesta ordem, as técnicas de difusão em ágar e microcultivo para leveduras. Resultados: Na técnica de difusão, o óleo essencial de S. aromaticum apresentou formação de halo de inibição para Candida krusei, Candida parapsilosis e Candida glabrata. O óleo de E. globulus, por sua vez, não apresentou crescimento de halos de inibição em nenhuma das concentrações testadas frente as três espécies de Candida não-albicans. Todavia, com o microcultivo, ambos os óleos essenciais se provaram, in vitro, eficazes antimicrobianos tendo apresentado estruturas indicativas de atividade antifúngica na maior concentração dos óleos e diferentes graus de destruição celular nas demais concentrações. Conclusão: Nas condições deste estudo, concluiu-se que os produtos avaliados exerceram atividade antifúngica contra cepas de Candida não-albicans, destacando-se o óleo essencial de S. aromaticum que apresentou atividade antimicrobiana em ambas as metodologias.
Análise da hemoglobina como modelo de estudo de interação droga-proteína in vitro e in silico
Authors: Teixeira Kádima Nayara , Peiter Gabrielle Caroline , Mota Vitor Hugo Sales da , Groto Anderson Dillmann , Assis Bianca Luiza Melo de
Published: July 2021

Modelo do estudo: Trata-se de um estudo experimental in vitro com abordagem computacional. Objetivo: Analisar a existência de interação entre as drogas hidrofóbicas bezafibrato e hidroclorotiazida com a hemoglobina a fim de prever alterações na biodisponibilidade das drogas, bem como na função proteica. Metodologia: Testes de interação in vitro entre a hemoglobina bovina e bezafibrato ou hidroclorotiazida foram realizados por espectrofotometria; análises dos sítios de interação e extrapolações para a hemoglobina humana foram feitas por técnicas de bioinformática. Resultados: Os testes in vitro demonstraram diminuição de absorbância (k) em 405 nm igual a 8,75 x 10-4 min-1 para o bezafibrato e 6,25 x 10-4 min--1 para a hidroclorotiazida. A diminuição sugere interação das drogas com a hemoglobina, sendo que o bezafibrato parece interagir com afinidade ligeiramente maior. As análises in silico mostraram que as drogas se ligam à porção proteica da hemoglobina. A constante de afinidade de ligação obtida por ancoragem molecular para o bezafibrato com a hemoglobina bovina (-8,3 kcal/mol) corrobora com o valor experimental de k e com o maior número de interações observadas, em relação à hidroclorotiazida (-6,6 kcal/mol). O mesmo padrão é observado para a interação do bezafibrato (-7,6 kcal/mol) e da hidroclorotiazida (-6,7 kcal/mol) com a hemoglobina humana. Conclusão: As técnicas de espectrofotometria e bioinformática utilizadas sugerem a possibilidade de interação da hemoglobina com drogas de natureza hidrofóbica, como bezafibrato e hidroclorotiazida, sendo que essa interação pode afetar a função normal da hemoglobina e alterar a farmacodinâmica e farmacocinética das drogas prejudicando sua eficiência terapêutica.
Uso de acervos de imagens em pesquisas na Odontologia Legal: reflexões éticas, bioéticas e legais
Authors: Silva Ricardo Henrique Alves da , Guimarães Marco Aurélio , Machado Ana Luísa Rezende , Borges Bruna Saud , Pinto Paulo Henrique Viana
Published: July 2021

Objetivo: Realizar um levantamento dos artigos científicos que utilizaram acervos de imagem como fonte de pesquisa em Odontologia Legal e discutir essa utilização sob perspectivas éticas, bioéticas e legais. Material e Métodos: Foi realizada uma busca de artigos científicos nas bases de dados Lilacs, PubMed e Scielo entre os anos de 2015 e 2019 utilizando descritores nos idiomas português, inglês e espanhol. Foram incluídos apenas artigos da área de Odontologia Legal que utilizaram acervos de imagem como fonte de informação. Foram excluídos estudos laboratoriais ou clínicos, arqueológicos ou antropológicos, relatos de caso ou artigos de revisão, estudos prospectivos ou que utilizaram exames de imagem não pertencentes a acervos. Resultados: Foram selecionados 171 artigos científicos. Desses, 22,80% (n=39) foram realizados por autores vinculados a instituições brasileiras, e 77,19% (n=132) mencionaram aprovação por comitê de ética em pesquisa ou instituição correspondente com (ou sem) necessidade de Termo de Consentimento Livre e Esclarecido (TCLE). Conclusão: Os acervos de imagem compreendem uma importante fonte de informação para pesquisas em Odontologia Legal dada a quantidade de publicações realizadas no período avaliado. A maioria dos artigos mencionou aprovação ética e respeito à privacidade dos participantes, conforme os requisitos estabelecidos para dispensa do TCLE.
Perfil dos usuários vivendo com HIV/Aids atendidos em um Centro de Testagem e Aconselhamento no interior da Bahia: um estudo longitudinal retrospectivo
Authors: Takenami Iukary , Gois Luana Leandro , Palácio Maria Augusta Vasconcelos , Medeiros Daiana Alencar de
Published: July 2021

Objetivo: Caracterizar o perfil clínico e epidemiológico dos usuários vivendo com HIV/Aids atendidos em um Centro de Testagem e Aconselhamento (CTA) localizado no município de Paulo Afonso, no interior da Bahia. Casuística e métodos: Estudo retrospectivo, observacional, baseado em dados secundários obtidos mediante consulta aos registros dos usuários cadastrados no serviço durante o período de 2002 a 2019. Os dados foram tratados e analisados por estatística descritiva e inferencial. Resultados: Foram identificados 301 indivíduos vivendo com HIV/Aids, correspondendo a uma média de 12,4 ± 9,5 casos/ano; 58,4% eram do sexo masculino com idade média de 40,6 ± 13,8 anos. Os indivíduos mais afetados possuíam o ensino fundamental incompleto e eram provenientes de bairros periféricos. Dos 226 indivíduos avaliados laboratorialmente, 49 (21,7%) foram diagnosticados na fase de Aids. Diferenças significativas foram observadas na contagem de linfócitos T CD4+, razão entre os linfócitos T CD4+/CD8+ e linfócitos T CD45+ entre indivíduos vivendo com HIV e aqueles diagnosticados na fase de Aids (p<0,001). Conclusão: A taxa de detecção de pessoas vivendo com HIV/Aids aumentou nos últimos anos no município de Paulo Afonso, Bahia. Esse aumento no número de casos deve-se, possivelmente, aos avanços nos métodos diagnósticos, bem como da implementação do CTA na região. O perfil dos indivíduos avaliados segue a tendência nacional, com predomínio do sexo masculino, jovem, com ensino fundamental incompleto. Como esperado, indivíduos diagnosticados na fase Aids apresentam resultados laboratoriais diferentes dos indivíduos vivendo com HIV.
percepção do usuário de um Centro de Atenção Psicossocial sobre a assistência em saúde mental
Authors: Barros Alice Correia , Silva John Victor dos Santos , Tszesnioski Luise de Cássia , Silva Lucas Kayzan Barbosa da , Santos Maria Zélia de Araújo Lessa
Published: July 2021

Introdução: Os Centros de Atenção Psicossocial são serviços especializados na assistência de indivíduos com transtornos mentais graves e persistentes e tem como finalidade trabalhar o processo de reabilitação psicossocial. Objetivo: Identificar a opinião do usuário sobre a assistência recebida em um Centro de Atenção Psicossocial de Maceió–AL. Método: Trata-se de um estudo do tipo descritivo com abordagem qualitativa realizado com 08 usuários de um CAPS de Maceió-AL, no mês de fevereiro de 2017, por meio de entrevista para coleta de material e análise de conteúdo para discussão dos resultados. Resultado: A partir das falas dos sujeitos surgiram as categorias “O CAPS na visão do usuário” e “Desafios e possibilidades para melhoria no CAPS”.  Conclusão: O estudo aponta para uma importância significativa desses serviços na saúde mental dos usuários e reconhecimento da necessidade do investimento de políticas públicas para melhoria da qualidade da assistência.
Avaliação do luto familiar na perda gestacional e neonatal
Authors: Nisihara Renato Mitsunori , Okamoto Cristina , Reda Somaia , Maia Natália Trench , Mendes Gabriele Belniowski , Pucci Carolina Meira , Trintinalha Mariana de Oliveira
Published: July 2021

Objetivos: Avaliar o grau de luto causado pela perda gestacional ou neonatal em pais e mães, associando com variáveis sócio-demográficas. Adicionalmente, comparar o grau de luto de acordo com o momento da perda. Métodos: Estudo transversal, realizado com aplicação de questionário sociodemográfico e questionário validado (Escala de Luto Perinatal–ELP) em pais que tiveram perda de seu filho em qualquer perído gestacional ou no neonatal. Resultados: 542 pais e mães estavam aptos para participação do estudo e após serem convidados para responder à pesquisa, 104 (19,1%) concordaram em participar. Os 104 participantes foram divididos em dois grupos: perda no primeiro trimestre gestacional (76,9%), e demais trimestres somados ao período neonatal (23,1%). Evidenciou-se predomínio materno das respostas (89,4%) e idade média de 29,1±15,58 anos.  A mediana do escore na ELP foi de 90 pontos, não havendo diferença entre as pontuações de acordo com o momento da perda. Primigestas e mulheres com idade <25 anos apresentaram pontuações maiores que as demais (p=0,042 e p=0,047). Ideação suicida foi relatada por 15,4% e 32,7% das mães que se culpam pela morte do bebê têm escores significativamente maior do que aquelas que não tinham tal sentimento (p<0,0001). Estado civil, escolaridade, situação econômica, religião, realização de pré-natal, etnia e abortamento prévio não apresentaram associação significativa com os escores obtidos na ELP. Conclusão: O luto ocorreu independente da idade gestacional do momento da perda, sendo de maior intensidade nas mulheres mais jovens e naquelas com sentimento de culpa. Medidas devem ser tomadas para minimizar tal sofrimento.
Association of Plasma Branched-Chain Amino Acid With Biomarkers of Inflammation and Lipid Metabolism in Women
Authors: Hamaya Rikuta , Mora Samia , Lawler Patrick R. , Cook Nancy R. , Ridker Paul M. , Buring Julie E. , Lee I-Min , Manson JoAnn E. , Tobias Deirdre K.
Published: July 2021

Background:

Branched-chain amino acids (BCAAs; isoleucine, leucine, and valine) correlate with insulin resistance and poor glucose control, which may in part explain associations between type 2 diabetes and cardiovascular disease. However, the relationships of BCAAs with other cardiometabolic pathways, including inflammation and dyslipidemia, are unclear. We hypothesized that plasma BCAAs would correlate with multiple pathways of cardiometabolic dysfunction.

Methods:

We conducted a cross-sectional analysis among 19 472 participants (mean age=54.9 years, SD=7.2 years) in the Women’s Health Study without a history of type 2 diabetes, cardiovascular disease, or cancer. We quantified the concentrations of individual biomarkers of inflammation and lipids, across quartiles of BCAAs, adjusting for age, smoking, body mass index, physical activity, and other established cardiovascular disease risk factors at blood draw.

Results:

Women in the highest versus lowest quartiles of plasma BCAAs had higher inflammatory markers including high-sensitivity C-reactive protein (multivariable-adjusted means: 1.96 versus 1.43 mg/L), fibrinogen (367 versus 362 mg/dL), soluble intercellular cell adhesion molecule-1 (361 versus 353 ng/mL), and glycoprotein acetylation (407 versus 371 µmol/L;
P
trend=0.0002 for fibrinogen;
P
<0.0001 for others). Similarly for lipids, women with higher BCAAs had lower HDL-C (high-density lipoprotein cholesterol; 49.0 versus 55.0 mg/dL), and higher triglycerides (143 versus 114 mg/dL), LDL-C (low-density lipoprotein cholesterol; 133 versus 124 mg/dL), and lipoprotein insulin resistance score (52.6 versus 37.3; all:
P
<0.0001). Similar associations with these biomarkers were observed in isoleucine, leucine, and valine, respectively.

Conclusions:

Higher circulating BCAA concentrations are associated with adverse profiles of biomarkers of inflammation and dyslipidemia independent of established cardiovascular disease risk factors, and thus, may reflect poorer cardiometabolic health through multiple pathways.

Registration:

URL:
https://www.clinicaltrials.gov
; Unique identifier: NCT00000479.
A Neuroligin Isoform Translated by circNlgn Contributes to Cardiac Remodeling
Authors: Du William W. , Xu Jindong , Yang Weining , Wu Nan , Li Feiya , Zhou Le , Wang Sheng , Li Xiangmin , He Alina T. , Du Kevin Y. , Zeng Kaixuan , Ma Jian , Lyu Juanjuan , Zhang Chao , Zhou Chi , Maksimovic Katarina , Yang Burton B.
Published: July 2021

Background:

Fibrotic cardiac remodeling is a maladaptive response to acute or chronic injury that leads to arrhythmia and progressive heart failure. The underlying mechanisms remain unclear. We performed high-throughput RNA sequencing to analyze circular RNA profile in human cardiac disease and developed transgenic mice to explore the roles of circNlgn.

Methods and Results:

Using RNA sequencing, we found that circular neuroligin RNA (circNlgn) was highly upregulated in myocardial tissues of patients with selected congenital heart defects with cardiac overload. Back-splicing of the neuroligin gene led to the translation of a circular RNA–derived peptide (Nlgn173) with a 9-amino-acid nuclear localization motif. Binding of this motif to the structural protein LaminB1 facilitated the nuclear localization of Nlgn173. CHIP analysis demonstrated subsequent binding of Nlgn173 to both ING4 (inhibitor of growth protein 4) and C8orf44-SGK3 (serum and glucocorticoid-inducible kinase-3) promoters, resulting in aberrant collagen deposition, cardiac fibroblast proliferation, and reduced cardiomyocyte viability. Three-dimensional ultrasound imaging of circNlgn-transgenic mice showed impaired left ventricular function, with further impairment when subjected to left ventricular pressure overload compared with WT (wild type) mice. Nuclear translocation of Nlgn173, dysregulated expression of ING4 and C8orf44-SGK3, and immunohistochemical markers of cardiac fibrosis were detected in a panel of 145 patient specimens. Phenotypic changes observed in left ventricular pressure overload and transgenic mice were abrogated with silencing of circNlgn or its targets ING4 and SGK3.

Conclusions:

We show that a circular RNA can be translated into a novel protein isoform. Dysregulation of this process contributes to fibrosis and heart failure in cardiac overload–induced remodeling. This mechanism may hold therapeutic implications for cardiac disease.
Therapeutic Inhibition of Acid-Sensing Ion Channel 1a Recovers Heart Function After Ischemia–Reperfusion Injury
Authors: Redd Meredith A. , Scheuer Sarah E. , Saez Natalie J. , Yoshikawa Yusuke , Chiu Han Sheng , Gao Ling , Hicks Mark , Villanueva Jeanette E. , Joshi Yashutosh , Chow Chun Yuen , Cuellar-Partida Gabriel , Peart Jason N. , See Hoe Louise E. , Chen Xiaoli , Sun Yuliangzi , Suen Jacky Y. , Hatch Robert J. , Rollo Ben , Xia Di , Alzubaidi Mubarak A.H. , Maljevic Snezana , Quaife-Ryan Gregory A. , Hudson James E. , Porrello Enzo R. , White Melanie Y. , Cordwell Stuart J. , Fraser John F. , Petrou Steven , Reichelt Melissa E. , Thomas Walter G. , King Glenn F. , Macdonald Peter S. , Palpant Nathan J.
Published: July 2021

Background:

Ischemia–reperfusion injury (IRI) is one of the major risk factors implicated in morbidity and mortality associated with cardiovascular disease. During cardiac ischemia, the buildup of acidic metabolites results in decreased intracellular and extracellular pH, which can reach as low as 6.0 to 6.5. The resulting tissue acidosis exacerbates ischemic injury and significantly affects cardiac function.

Methods:

We used genetic and pharmacologic methods to investigate the role of acid-sensing ion channel 1a (ASIC1a) in cardiac IRI at the cellular and whole-organ level. Human induced pluripotent stem cell–derived cardiomyocytes as well as ex vivo and in vivo models of IRI were used to test the efficacy of ASIC1a inhibitors as pre- and postconditioning therapeutic agents.

Results:

Analysis of human complex trait genetics indicates that variants in the
ASIC1
genetic locus are significantly associated with cardiac and cerebrovascular ischemic injuries. Using human induced pluripotent stem cell–derived cardiomyocytes in vitro and murine ex vivo heart models, we demonstrate that genetic ablation of ASIC1a improves cardiomyocyte viability after acute IRI. Therapeutic blockade of ASIC1a using specific and potent pharmacologic inhibitors recapitulates this cardioprotective effect. We used an in vivo model of myocardial infarction and 2 models of ex vivo donor heart procurement and storage as clinical models to show that ASIC1a inhibition improves post-IRI cardiac viability. Use of ASIC1a inhibitors as preconditioning or postconditioning agents provided equivalent cardioprotection to benchmark drugs, including the sodium-hydrogen exchange inhibitor zoniporide. At the cellular and whole organ level, we show that acute exposure to ASIC1a inhibitors has no effect on cardiac ion channels regulating baseline electromechanical coupling and physiologic performance.

Conclusions:

Our data provide compelling evidence for a novel pharmacologic strategy involving ASIC1a blockade as a cardioprotective therapy to improve the viability of hearts subjected to IRI.
International Observational Analysis of Evolution and Outcomes of Chronic Stable Angina: The Multinational CLARIFY Study
Authors: Mesnier Jules , Ducrocq Gregory , Danchin Nicolas , Ferrari Roberto , Ford Ian , Tardif Jean-Claude , Tendera Michal , Fox Kim M. , Steg Philippe Gabriel ,   for the CLARIFY Investigators
Published: July 2021

Background:

Although angina is common in patients with stable coronary artery disease, limited data are available on its prevalence, natural evolution, and outcomes in the era of effective cardiovascular drugs and widespread use of coronary revascularization.

Methods:

Using data from 32 691 patients with stable coronary artery disease from the prospective observational CLARIFY registry (Prospective Observational Longitudinal Registry of Patients with Stable Coronary Artery Disease), anginal status was mapped each year in patients without new coronary revascularization or new myocardial infarction. The use of medical interventions in the year preceding angina resolution was explored. The effect of 1-year changes in angina status on 5-year outcomes was analyzed using multivariable analysis.

Results:

Among 7212 (22.1%) patients who reported angina at baseline, angina disappeared (without coronary revascularization) in 39.6% at 1 year, with further annual decreases. In patients without angina at baseline, 2.0% to 4.8% developed angina each year. During 5-year follow-up, angina was controlled in 7773 patients, in whom resolution of angina was obtained with increased use of antianginal treatment in 11.1%, with coronary revascularization in 4.5%, and without any changes in medication or revascularization in 84.4%. Compared to patients without angina at baseline and 1 year, persistence of angina and occurrence of angina at 1 year with conservative management were each independently associated with higher rates of cardiovascular death or myocardial infarction (adjusted hazard ratio, 1.32 [95% CI, 1.12−1.55] for persistence of angina; adjusted hazard ratio, 1.37 [95% CI, 1.11−1.70] for occurrence of angina) at 5 years. Patients whose angina had resolved at 1 year with conservative management were not at higher risk of cardiovascular death or myocardial infarction than those who never experienced angina (adjusted hazard ratio, 0.97 [95% CI, 0.82−1.15]).

Conclusions:

Angina affects almost one-quarter of patients with stable coronary artery disease but resolves without events or coronary revascularization in most patients. Resolution of angina within 1 year with conservative management predicted outcomes similar to lack of angina, whereas persistence or occurrence was associated with worse outcomes. Because most patients with angina are likely to experience resolution of symptoms, and because there is no demonstrated outcome benefit to routine revascularization, this study emphasizes the value of conservative management of stable coronary artery disease.

Registration:

URL:
https://www.isrctn.com
; Unique identifier: ISRCTN43070564.
Decoupling the Role of Data, Attention, and Losses in Multimodal Transformers
Authors: Hendricks Lisa Anne , Mellor John , Schneider Rosalia , Alayrac Jean-Baptiste , Nematzadeh Aida
Published: July 2021

Recently, multimodal transformer models have gained popularity because their performance on downstream tasks suggests they learn rich visual-linguistic representations. Focusing on zero-shot image retrieval tasks, we study three important factors that can impact the quality of learned representations: pretraining data, the attention mechanism, and loss functions. By pretraining models on six datasets, we observe that dataset noise and language similarity to our downstream task are important indicators of model performance. Through architectural analysis, we learn that models with a multimodal attention mechanism can outperform deeper models with modality-specific attention mechanisms. Finally, we show that successful contrastive losses used in the self-supervised learning literature do not yield similar performance gains when used in multimodal transformers.