bluuebunny/crossref_metadata_2025 huggingface dataset:
Multimodal Imaging Features of Bilateral Choroidal Ganglioneuroma
Authors: Jiang Zhaoxin , Zhang Ting , Liu Xing , Liang Dan , Zhong Yimin , Chan Chi-chao , Ding Xiaoyan
Published: May 2020

Purpose. Bilateral choroidal ganglioneuroma is extremely rare, and no cases have been described in the literature. Multimodal images are crucial for its diagnosis. Here, we evaluated multimodal images in the early stage of choroidal ganglioneuroma. Methods. A 6-year-old boy was recruited who had experienced gradually progressive vision loss and rapidly progressive myopia in both eyes over the past 2 years. His eyes were comprehensively evaluated via slit-lamp microscopy, ultrasound biomicroscopy, swept-source optical coherence tomography (SS-OCT), fundoscopy, fundus fluorescein angiography, indocyanine green angiography (ICGA), ultrasound B scanning, and magnetic resonance imaging. Electrophysiological examinations included electrooculography and electroretinography. Choroid biopsy and pathological examination were performed. Results. Over the past 2 years, the patient’s best-corrected visual acuity had gradually decreased to hand motions at 10 cm in the right eye and 20/63 in the left, with axial length growth to 25.89 mm in the right and 28.99 mm in the left. Diffuse thickening in bilateral eyewalls was depicted in B scanning and magnetic resonance imaging. Secondary exudative retinal detachment was evident in SS-OCT and B scanning. SS-OCT depicted low optical reflections in the choroidal layer, revealing a lack of choroidal vasculature. Diffuse hypofluorescence in ICGA photography confirmed extensive loss of choroidal vasculature. In electrophysiological function investigations, electrooculography revealed remarkable bilateral low Arden ratios, with almost extinguished electroretinogram in the right eye. Right-eye choroid biopsy was performed, resulting in a histological diagnosis of choroidal ganglioneuroma. Conclusion. Choroidal ganglioneuroma is rare. To our knowledge, no bilateral cases have been described in the literature. Major clinical features include a rapid increase in axial length, diffuse choroidal thickening, hyper-reflectivity in the choroid on optical coherence tomography, and loss of choroidal vasculature on ICGA. The current report provides multimodal imaging of choroidal ganglioneuroma for the first time and can be valuable for early diagnosis.
Chemical, Microbiological, and Functional Characterization of Kefir Produced from Cow’s Milk and Soy Milk
Authors: Gamba Raúl Ricardo , Yamamoto Shihori , Abdel-Hamid Mahmoud , Sasaki Tetsuya , Michihata Toshihide , Koyanagi Takashi , Enomoto Toshiki
Published: May 2020

Kefir is a functional beverage that contains lactic and acetic acid bacteria (LAB, AAB) and yeasts. This work’s aim was to study the chemical, microbial, and functional characteristics of kefir produced from cow’s milk and soy milk. After fermentation, free amino acids were 20.92 mg 100 mL−1and 36.20 mg 100 mL−1for cow’s milk and soy milk kefir, respectively. Glutamic acid was majority in both, suggesting that microbial proteolysis leads to an increase in free amino acids including glutamic acid. 108–109 CFU mL−1LAB, 106–107 CFU mL−1AAB, and 106–107 CFU mL−1yeasts were counted in cow’s milk kefir, whereas soy milk kefir contained greatly lower yeasts and AAB.Lactococcus lactis,Kazachstania unispora, andSaccharomyces cerevisiaewere isolated as major microorganisms in both kefirs.Acetobacter orientalisonly existed in cow’s milk kefir. Cow’s milk and soy milk showed ACE inhibitory activity, which significantly increased after fermentation. Both kefirs also exhibited antioxidant activity and bactericidal activity againstEscherichia coli,SalmonellaTyphimurium, andStaphylococcus aureus.
Modeling and Prediction Method for CNC Machine Tools’ Errors Based on Spatial Feature Points
Authors: Chen Guohua , Zhang Lin , Xiang Hua , Chen Yong
Published: May 2020

In order to improve the precision of CNC machine tools effectively, a method for modeling and predicting their spatial errors based on spatial feature points was proposed. Taking three‐axis vertical CNC machine tools as the research object, we think that the whole space formed by machine tools’ working can be seen as the combination of a number of cubes, whose vertices are considered to be feature points, and others in the cubes are called nonfeature points. So, each nonfeature point’s errors can be predicted by the cube’s eight vertices’ errors. Based on the above ideas, an approach including the installing instrument for measuring any spatial feature point’s errors was put forward. In this way, all data of the feature points’ errors could be obtained. Moreover, according to these error data, the prediction model of nonfeature points’ errors was established by using the internal division ratio method. The method has the advantages of small interpolation operation, easy integration in the numerical control system, and high compensation precision. Finally, an example was used to prove its effectiveness and feasibility.
Notch-Hes1 Signaling Regulates IL-17A+γδ+T Cell Expression and IL-17A Secretion of Mouse Psoriasis-Like Skin Inflammation
Authors: Wang Yanqin , Li Xinxin , Xing Xiaoyun , Xue Haibo , Qi Ruiqun , Ji Hong , Ma Lei
Published: May 2020

Purpose. To evaluate the regulating effect of Notch-Hes1 signaling on IL-17A+γδ+T cell expression and IL-17A secretion in mouse psoriasis-like skin inflammation. Materials and Methods. Experimental mice were randomly divided into control group, model group (5% imiquimod- (IMQ-) treated mice), and intervention group (IMQ and γ-secretase inhibitor DAPT cotreated mice). The severity of psoriasis-like skin inflammation was evaluated by target lesion score based on the clinical psoriasis area and severity index (PASI). Flow cytometry detected IL-17A+γδ+T cell percentage. Quantitative real-time RT-PCR detected Hes1 mRNA expression. Enzyme-linked immunosorbent assay and western blot measured IL-17A serum concentration and protein expression. Additionally, splenic single cells from model mice were treated by DAPT to further evaluate the inhibitory effect of blocking Notch-Hes1 signaling on IL-17A+γδ+T cell differentiation and IL-17A secretion. Results. The spleen index, IL-17A+γδ+T cell percentage, Hes1 mRNA expression, IL-17A serum concentration, and protein expression were all significantly higher in model mice than control mice, while dramatically reduced in intervention mice by DAPT treatment, which also obviously alleviated the target lesion score, epidermal hyperplasia, and dermal inflammatory cell infiltration of intervention mice. In vitro study demonstrated that DAPT treatment could result in dose-dependent decrease of IL-17A+γδ+T cell percentage and IL-17A secretion in splenic single cells of model mice.
A Least Cumulative Ventilation Cost Method for Urban Ventilation Environment Analysis
Authors: Xie Peng , Liu Dianfeng , Liu Yanfang , Liu Yaolin
Published: May 2020

The correct urban building layout is an important influencing factor in urban ventilation, and the heat island effect has become an important factor affecting the quality of urban life. Optimization of the urban building layout can play a role in mitigating the heat island effect. The traditional ventilation corridor analysis method, based on a least-cost path analysis, can only generate a few main ventilation corridors. It is difficult to obtain global ventilation results covering the whole study area using this method of analysis. On the basis of urban morphology and a least-cost path analysis, this study proposes a “least cumulative ventilation cost” method for analyzing urban ventilation. Taking Wuhan downtown as a research area, the urban ventilation environment under different wind directions and seasons was analyzed. This method can effectively express the ventilation conditions throughout the whole study area and can simultaneously express the quality of the generated corridors effectively. The results show that Wuhan has three levels of ventilation corridor. Moreover, the ventilation conditions in Wuchang (Wuchang, Qingshan, and Hongshan) are better than those in Hankou (Qiaokou, Jianghan, and Jiang’an).
Differentiation of Pelvic Osteosarcoma and Ewing Sarcoma Using Radiomic Analysis Based on T2‐Weighted Images and Contrast‐Enhanced T1‐Weighted Images
Authors: Dai Yi , Yin Ping , Mao Ning , Sun Chao , Wu Jiangfen , Cheng Guanxun , Hong Nan
Published: May 2020

Objective. To determine if osteosarcoma (OS) and Ewing sarcoma (EWS) of the pelvis based on MRI can be differentiated using radiomic analysis. Materials and Methods. In this study, 3.0 T magnetic resonance (MR) data of 66 patients (40 males and 26 females, mean age 27.6 ± 13.9 years) with pathologically confirmed OS or EWS of the pelvis (35 with OS and 31 with EWS) taken from April 2013 to December 2017 were retrospectively reviewed. T2‐weighted fat‐saturated (T2‐FS) and contrast‐enhanced T1‐weighted (CET1) images were manually segmented, and imaging features were extracted. Independent‐sample t‐test, Spearman’s test, and the least absolute shrinkage and selection operator (LASSO) method were used to select the most useful features from the original data set. The performance of radiomic analysis was investigated by the area under the receiver operating characteristic (ROC) curve (AUC) analysis. Results. 385 initial features were extracted from T2‐FS and CET1 MR data. Nine features from T2‐FS and 7 features from CET1 were selected by using the LASSO method. The radiomic analysis to differentiate OS and EWS of the pelvis based on T2‐FS and CET1 images using the aforementioned selected features achieved AUC values of 0.881 (95% confidence interval (CI): 0.799–0.963) and 0.765 (95% CI: 0.652–0.878), respectively. Conclusion. Radiomic analysis showed potential in differentiating OS from EWS of the pelvis, in which T2‐FS demonstrated better diagnostic value. To differentiate OS from EWS of the pelvis using our multiparametric MRI‐based radiomic analysis could preoperatively improve diagnostic accuracy and greatly contribute to therapy planning.
Food Hygiene Practices at the Ghana School Feeding Programme in Wa and Cape Coast Cities
Authors: Bigson Kate , Essuman Edward Ken , Lotse Comfort Worna
Published: May 2020

Objective. The integrity and the wholesomeness of the food served to school pupils cannot be overlooked, especially when one considers the magnitude of health and sanitation issues that are plaguing the West African nations. This study aimed to investigate some of the personal hygiene practices by the pupils and the hygienic conditions in which food is cooked and served to these school-going children under the Ghana School Feeding Programme (GSFP). Design. A cross-sectional and descriptive survey research designs were used in the study. Purposive and simple random sampling techniques were employed in selecting participants. Participants. There were 720 respondents for the study, comprising 600 pupils, 60 teachers, and 60 kitchen staff members from 20 schools. Information was obtained using questionnaire, observation, and unstructured interview instruments. Results. Findings from the study revealed that the majority of pupils (92% in Wa and 65% in Cape Coast) did not wash their hands with soap under running water. No hand washing centers for pupils were also seen in most of the schools studied. Majority of the cooks did not have health certificate, and neither had attended any in-service training in two years. In both Wa and Cape Coast municipal schools, none of the kitchen staff admitted that pupils and teachers ever complained about the meals they served to the pupils. Conclusion. The GSFP in basic schools forms part of the integral diet of the school children; hence, provision of good quality food can affect the health, learning, and physical activities of these children. Observational checklist revealed that most of the kitchen staff do not strictly adhere to basic food hygiene practices, and this affects the wholesomeness of the food served to the children. There is, therefore, a need for kitchen staff training on hygiene and food preparation practices.
Object Detection with the Addition of New Classes Based on the Method of RNOL
Authors: Fang Haiquan , Zhu Feijia
Published: May 2020

Object detection plays an important role in many computer vision applications. Innovative object detection methods based on deep learning such as Faster R-CNN, YOLO, and SSD have achieved state-of the-art results in terms of detection accuracy. There have been few studies to date on object detection with the addition of new classes, however, though this problem is often encountered in the industry. Therefore, this issue has important research significance and practical value. On the premise that the old class samples are available, a method of reserving nodes in advance in the output layer (RNOL) was established in this study. Experiments show that RNOL can achieve high detection accuracy in both new and old classes over a short training time while outperforming the traditional fine-tuning method.
Intelligent Diagnosis of Heart Murmurs in Children with Congenital Heart Disease
Authors: Wang Jiaming , You Tao , Yi Kang , Gong Yaqin , Xie Qilian , Qu Fei , Wang Bangzhou , He Zhaoming
Published: May 2020

Heart auscultation is a convenient tool for early diagnosis of heart diseases and is being developed to be an intelligent tool used in online medicine. Currently, there are few studies on intelligent diagnosis of pediatric murmurs due to congenital heart disease (CHD). The purpose of the study was to develop a method of intelligent diagnosis of pediatric CHD murmurs. Phonocardiogram (PCG) signals of 86 children were recorded with 24 children having normal heart sounds and 62 children having CHD murmurs. A segmentation method based on the discrete wavelet transform combined with Hadamard product was implemented to locate the first and the second heart sounds from the PCG signal. Ten features specific to CHD murmurs were extracted as the input of classifier after segmentation. Eighty-six artificial neural network classifiers were composed into a classification system to identify CHD murmurs. The accuracy, sensitivity, and specificity of diagnosis for heart murmurs were 93%, 93.5%, and 91.7%, respectively. In conclusion, a method of intelligent diagnosis of pediatric CHD murmurs is developed successfully and can be used for online screening of CHD in children.
The Effect of Helicobacter pylori Eradication in Patients with Gastroesophageal Reflux Disease: A Meta-Analysis of Randomized Controlled Studies
Authors: Zhao Yan , Li Yarui , Hu Junbi , Wang Xin , Ren Mudan , Lu Guifang , Lu Xinlan , Zhang Dan , He Shuixiang
Published: May 2020

Aim: Helicobacter pylori infection has been established as a definite risk factor for gastric cancer. However, the consequence of H. pylori eradication on the progression of gastroesophageal reflux disease (GERD) remains controversial. The purpose of our study was to investigate the relationship between H. pylori eradication and the development of GERD. Methods: A comprehensive, English literature search was performed from January 1990 to April 2019. Only randomized controlled trials (RCT) that evaluated the effect of H. pylori eradication on GERD were included. Meta-analysis of pooled OR was performed using Review Manger 5.1.7. Results: Seventeen articles with 6,889 subjects (intention-to-treat) that fulfilled the inclusion criteria were finally included in the analysis. Of them, 8 RCTs have the similar study design and inclusion criterion, which included patients with H. pylori infection but without GERD at baseline. The OR for the development of erosive GERD after H. pylori eradication was 1.67 (95% CI 1.12–2.48, p = 0.01). The OR for the development of GERD-related symptoms after H. pylori eradication in eradication group compared with control group was 1.04 (95% CI 0.84–1.29, p = 0.71). In addition, 9 RCTs included patients with both baseline H. pylori infection and GERD. The OR for the healing rates and relapse rates after H. pylori eradication in the H. pylori eradication group vs. control group was 0.92 (95% CI 0.47–1.82, p = 0.82) and 1.12 (95% CI 0.60–2.09, p = 0.71), respectively. Conclusions: Our meta-analyses showed H. pylori eradication may lead to the development of new erosive GERD. However, eradication of H. pylori may affect neither the healing rates nor relapse rates of preexisting GERD.
Cumulative Evidence for Association of Acetaminophen Exposure and Allergic Rhinitis
Authors: Zeng Yan , Song Bin , Gao Yang , Cao Wen , Li Jia , Liu Qianfang , Liu Jian
Published: May 2020

Background: Several studies have linked acetaminophen exposure to the risk of allergic rhinitis, with controversial results. Methods: A systematic search of PubMed, Embase, Cochrane Library, and Web of Science was conducted up to December 1, 2019. We included observational studies that examined the association between acetaminophen exposure and the risk of allergic rhinitis. Two reviewers independently extracted data and assessed study quality. Summary odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using random-effects meta-analysis. Results: Eighteen studies with 870,492 participants were included. Analysis showed that acetaminophen exposure was associated with an increased risk of allergic rhinitis (OR: 1.54, 95% CI: 1.41–1.69). Also, early exposure and exposure in the past year to acetaminophen was positively associated with risk of allergic rhinitis (OR: 1.34, 95% CI: 1.21–1.49 and OR: 1.74, 95% CI: 1.48–2.04, respectively). The risk of allergic rhinitis was greater for people who had acetaminophen exposure once per month over the past year (OR: 1.90, 95% CI: 1.60–2.26) compared to once per year (OR: 1.28, 95% CI: 1.11–1.48). Conclusion: With our meta-analysis, we provide the evidence that exposure to acetaminophen is associated with an increased risk of allergic rhinitis. In addition, acetaminophen exposure in early life and acetaminophen exposure in the past year are positively associated with the risk of allergic rhinitis. Future research is needed to evaluate whether the association is causal.
A Comparison of UK Preterm Anthropometric Charts and INTERGROWTH-21st: Is It Time to Change Growth Charts?
Authors: Bendor-Samuel Owen Martyn , Zivanovic Sanja , Odd David , Roehr Charles Christoph
Published: May 2020

Background: Current practice in the UK is to plot premature infant anthropometric measurements on Neonatal and Infant Close Monitoring (NICM) reference charts. These charts have several known limitations. The INTERGROWTH-21st Project has recently produced international ante- and postnatal growth standards. Exact knowledge of growth centiles allows clinicians to accurately assess infant nutritional requirements. Objective: To compare target centile measurements between INTERGROWTH-21st and UK NICM growth charts for premature infants. Method: Anthropometric measurements (weight and head circumference) of a convenience sample of neonates born between 24 and 32 weeks of gestation were analysed retrospectively. Measurements were collected across three time points and plotted on both the NICM and INTERGROWTH-21st growth charts. The respective centiles were compared and analysed by paired-sample t test, Wilcoxon rank test analysis, and multilevel mixed-effect linear regression models. Results: Centiles for weight and head circumference measurements of 96 infants plotted on INTERGROWTH-21st charts were significantly greater than their corresponding UK charts at all three time points. For weight, the average difference between the two charts varied from 9.1 to 16.4 centiles. The difference between the two charts was greater for female than male infants by up to 6.9 centiles (95% CI 10.1–3.8). Conclusion: Existing UK NICM reference charts are significantly different to the growth standards of INTERGROWTH-21st. The choice of which growth chart to adopt in the UK could have important consequences on premature infants’ future adult health and therefore requires further prospective observational studies with larger data sets including length measurements and more comprehensive population characteristics.
Exploring the Role of Piperacillin and Tazobactam in Combination with Vancomycin against Methicillin-Resistant Staphylococcus aureus
Authors: Dilworth Thomas J. , Sanchez Daniel , Anderson Beverly , DeAngelis Haedi , Mercier Renée-Claude
Published: May 2020

Previous studies have demonstrated synergy between piperacillin (PIP)-tazobactam (TAZ) (TZP) and vancomycin (VAN) against methicillin-resistant Staphylococcus aureus (MRSA). However, it is unknown whether PIP and/or TAZ synergizes with VAN against MRSA. We sought to determine whether PIP and/or TAZ synergizes with VAN against MRSA in vitro. The activity of PIP and/or TAZ with and without VAN (1/2 the minimum inhibitory concentration) was tested against 5 clinical MRSA isolates using a 24-h time-kill methodology. Antibiotic susceptibilities, accessory gene regulator (agr) operon functionality, and US strain type were also determined for the isolates. The combination of VAN and TZP was bactericidal against 3/5 isolates and synergistic against 4/5 isolates tested. Neither PIP nor TAZ alone combined with VAN demonstrated a significant reduction in bacterial growth. The combination of TZP and VAN was less active against the lone isolate with agr dysfunction. In summation, the combination of VAN with both PIP and TAZ was required for synergy against MRSA. This antibiotic combination may not be effective against unique MRSA strain types.
Variations in the Management of Cervical Thoracic Duct Cyst
Authors: Abelardo Edgardo , Shastri Priyanka , Prabhu Vinod
Published: May 2020

We present an uncomplicated case report of a cervical thoracic duct cyst (CTDC) in a 61-year-old woman treated with surgical excision. We reviewed 47 similar cases since it was first described in 1964 and evaluated the different diagnostic and management approaches. Previously believed to be the gold standard tool for evaluation, lymphangiography is now less popular due to advent of high-resolution imaging combined with aspiration techniques. CTDC treatment includes observation, low-fat diet, repeated aspirations, external pressure, sclerotherapy, embolisation, and surgical intervention. The preferred management of choice to date is surgical excision.
Challenges of New Approaches in Metastatic Merkel Cell Carcinoma
Authors: Monteiro Ana , Gouveia Emanuel , Garcez Daniela , Donato Sara , Martins-Branco Diogo , Marques Joana , Nunes Hugo , Passos Maria José , Clara Ana Isabel , Moreira António
Published: May 2020

Merkel cell carcinoma is a rare and aggressive cutaneous tumor, and the use of checkpoint inhibitors immunotherapy is a recent indication in its metastatic setting, both first and second line. However, the widespread use of immunotherapy is associated with an increase of acute and late immune-mediated adverse events. We present a case of an elderly fit patient with metastatic Merkel cell carcinoma treated with pembrolizumab who developed diabetic ketoacidosis, a severe immune-mediated adverse event. A multidisciplinary approach was crucial to overcome the life-threatening event. Even with early treatment stop, the patient had a significant and durable response to the treatment for 15 months. Meanwhile, a progressive pan-cerebellar syndrome emerged, possible due to a paraneoplastic syndrome with a negative onco-neuronal antibody panel, although an autoimmune etiology associated with immunotherapy could not be excluded. Unfortunately, the situation was irreversible and refractory to immunomodulatory treatment. Despite the unpredictable toxicity, it is important to note the efficacy profile, with a progression-free survival of 15 months, which is higher than the one reported in reference clinical trials in this setting.
Hemophagocytic Lymphohistiocytosis Secondary to PD-1 and IDO Inhibition in a Patient with Refractory Glioblastoma
Authors: Thummalapalli Rohit , Heumann Thatcher , Stein Julie , Khan Sarah , Priemer David S. , Duffield Amy S. , Laterra John , Couzi Rima , Lim Michael , Holdhoff Matthias
Published: May 2020

Immune checkpoint inhibition (ICI)-based approaches have transformed the treatment landscape of numerous solid tumors. Glioblastoma (GBM) is an aggressive and almost universally fatal disease which is in need of novel treatment options, and combinations of immune checkpoint inhibitors, including dual agent therapy, are starting to be explored in refractory GBM. Growing adoption of ICI-based approaches in solid tumors has been met with improved understanding of immune-related adverse events (IRAEs), including primary hematologic adverse events. Although management guidelines for multiple hematologic IRAEs have been established, the emergence of hemophagocytic lymphohistiocytosis (HLH) secondary to ICI therapy has only rarely been described, and its pathogenesis and optimal management are incompletely understood. We present the case of a 74-year-old male with a history of refractory GBM treated with PD-1 and indoleamine-pyrrole 2,3-dioxygenase (IDO) inhibition who experienced acute liver injury, followed by progressive fevers, altered mental status, and cytopenias. Serum studies and examination of spleen and bone marrow pathology were consistent with HLH, which was refractory to steroids and ultimately resulted in his rapid clinical decline. Here, we review prior cases of HLH secondary to ICI therapy across solid tumors, and explore potential mechanisms contributing to the rapid onset and refractory nature of our patient’s HLH syndrome. We hope to further highlight HLH as an emerging hematologic IRAE secondary to ICI therapy, and suggest that new practice guidelines begin to recognize HLH as a characteristic hematologic IRAE in patients treated with PD-1 and other immune checkpoint inhibitors.
Established and Novel Mechanisms Leading to de novo Genomic Rearrangements in the Human Germline
Authors: Hattori Atsushi , Fukami Maki
Published: May 2020

During gametogenesis, the human genome can acquire various de novo rearrangements. Most constitutional genomic rearrangements are created through 1 of the 4 well-known mechanisms, i.e., nonallelic homologous recombination, erroneous repair after double-strand DNA breaks, replication errors, and retrotransposition. However, recent studies have identified 2 types of extremely complex rearrangements that cannot be simply explained by these mechanisms. The first type consists of chaotic structural changes in 1 or a few chromosomes that result from “chromoanagenesis (an umbrella term that covers chromothripsis, chromoanasynthesis, and chromoplexy).” The other type is large independent rearrangements in multiple chromosomes indicative of “transient multifocal genomic crisis.” Germline chromoanagenesis (chromothripsis) likely occurs predominantly during spermatogenesis or postzygotic embryogenesis, while multifocal genomic crisis appears to be limited to a specific time window during oogenesis and early embryogenesis or during spermatogenesis. This review article introduces the current understanding of the molecular basis of de novo rearrangements in the germline.
Spatiotemporal Expression of Foxl2 and Dmrt1 before, during, and after Sex Determination in the Sea Turtle Lepidochelys olivacea
Authors: Díaz-Hernández Verónica , Dominguez-Mora Paloma , Chino-Palomo Luis , Marmolejo-Valencia Alejandro , Harfush Martha , Merchant-Larios Horacio
Published: May 2020

The sex of sea turtles is determined by temperature during egg incubation. Thus, climate change affects the sex ratio, exacerbating their vulnerability to extinction. Understanding spatiotemporal effects of temperature on sex determination at the gonadal level may facilitate the design of strategies to mitigate the effects of global warming. Here, we used qRT-PCR and immunofluorescence to analyze the spatiotemporal expression of Dmrt1 and Foxl2 in developing gonads of Lepidochelys olivacea incubated at male-producing temperature (MPT, 26°C) or female-producing temperature (FPT, 33°C). Although both transcription factors are expressed in bipotential gonads up to stage 25, the timing of their sexually dimorphic regulation differs. Whereas the dimorphic expression of Dmrt1 protein initiates at stage 24, Foxl2 protein was expressed specifically in females at stage 25. Interestingly, whereas Dmrt1 colocalizes with Sox9 in cell nuclei of primary medullary cords to form the testis cords, Foxl2 protein is first detected in Sox9-negative cells of primary medullary cords, prior to its substantial expression in the ovarian cortex. Thus, results suggest that the temperature-dependent regulation of sexual pathways is stochastic among the cells of primary medullary cords in undifferentiated bipotential gonads of the olive ridley.
Systemische Sklerose: Den prognostischen Wert von kardiopulmonalen Belastungstests erkennen
Authors: Krüger Stefan
Published: May 2020

Background: Systemic sclerosis (SSc) is a severe rheumatic disease of the interstitial tissue, in which heart and lung involvement can lead to disease-specific mortality. Our study tests the hypothesis that in addition to established prognostic factors, cardiopulmonary exercise testing (CPET) parameters, particularly peak oxygen uptake (peakVO2) and ventilation/carbon dioxide (VE/VCO2)-slope, can predict survival in patients with SSc. Subjects and methods: We retrospectively assessed 210 patients (80.9% female) in 6 centres over 10 years with pulmonary testing and CPET. Survival was analysed with Cox regression analysis (adjusted for age and gender) by age, comorbidity (Charlson-Index), body weight, body-mass index, extensive interstitial lung disease, pulmonary artery pressure (measured by echocardiography and invasively), and haemodynamic, pulmonary and CPET parameters. Results: Five- and ten-year survival of SSc patients was 93.8 and 86.9%, respectively. There was no difference in survival between patients with diffuse (dcSSc) and limited cutaneous manifestation (lcSSc; p = 0.3). Pulmonary and CPET parameters were significantly impaired. Prognosis was worst for patients with pulmonary hypertension (p = 0.007), 6-min walking distance < 413m (p = 0.003), peakVO2 < 15.6 mL•kg− 1•min− 1, and VE/VCO2-slope > 35. Age (hazard ratio HR = 1.23; 95% confidence interval CI: 1.14;1.41), VE/VCO2-slope (HR = 0.9; CI 0.82;0.98), diffusion capacity (Krogh factor, HR = 0.92; CI 0.86;0.98), forced vital capacity (FVC, HR = 0.91; CI 0.86;0.96), and peakVO2 (HR = 0.87; CI 0.81;0.94) were significantly linked to survival in multivariate analyses (Harrell’s C = 0.95). Summary: This is the first large study with SSc patients that demonstrates the prognostic value of peakVO2 < 15.6 mL•kg− 1•min− 1 (< 64.5% of predicted peakVO2) and VE/VCO2-slope > 35.
Prospective Evaluation of the Accuracy of A Training Program in Image Recognition by Narrow-Band Imaging Guided Hysteroscopy of Endometrial Neoplasms
Authors: Wang Wenli , Chen Fang , Kong Liang , Guo Yinshu , Cheng Jiumei , Zhang Ying
Published: May 2020

Introduction: Narrow-band imaging (NBI) hysteroscopy by experienced hysteroscopists (EH) is useful for diagnosing endometrial neoplasms. Objective: We investigated whether the diagnostic reliability of NBI could be improved by specific professional training. Methods: Three levels of trainees who were Surgeons at our hospital were selected. Level I: 6 trainees had no prior hysteroscopic experience; level II: 6 trainees had experience with <100 cases; and level III: 6 trainees had <500 cases. The two-hour training program for white light hysteroscopy (WLH) and NBI included information on the classifications of diseases of the uterine cavity and on the features of diagnostic images. Images from 529 patients were evaluated independently by trainees with 3 levels of before and after training, and by EH. Trainees and EHs had to analyze and arrive at a hysteroscopic diagnosis for each image that was compared to the pathological diagnosis for diagnostic accuracy. Results: After training, all levels achieved higher diagnostic accuracy with NBI than was seen with WLH. Level III trainees achieved diagnostic accuracy and kappa values for NBI that were equivalent to those of EH. Conclusions: Training can increase the diagnostic skill of all trainees using NBI, especially for trainees with prior hysteroscopic experience.
Improving Cost-effectiveness and Access to Cognitive Behavior Therapy for Depression: Providing Remote-Ready, Computer-Assisted Psychotherapy in Times of Crisis and Beyond
Authors: Thase Michael E. , McCrone Paul , Barrett Marna S. , Eells Tracy D. , Wisniewski Stephen R. , Balasubramani G.K. , Brown Gregory K. , Wright Jesse H.
Published: May 2020

Introduction: There is growing evidence that computer-delivered or computer-assisted forms of cognitive behavior therapy (CCBT) are helpful, but cost-effectiveness versus standard therapies is not well established. Objective: To evaluate the cost-effectiveness of a therapist-supported method for CCBT in comparison to standard cognitive behavior therapy (CBT). Methods: A total of 154 drug-free major depressive disorder outpatients were randomly assigned to either 16 weeks of standard CBT (up to twenty 50-min sessions) or CCBT using the Good Days Ahead program (including up to 5.5 h of therapist contact). Outcomes were assessed at baseline, weeks 8 and 16, and at 3 and 6 months post-treatment. Economic analyses took into account the costs of services received and work/social role impairment. Results: In the context of almost identical efficacy, a form of CCBT that used only about one third the amount of therapist contact as conventional CBT was highly cost-effective compared to conventional therapy and reduced the adjusted cost of treatment by USD 945 per patient. Conclusions: A method of CCBT that blended internet-delivered modules and abbreviated therapeutic contact reduced the cost of treatment substantially without adversely affecting outcomes. Results suggest that use of this approach can more than double the access to CBT. Because clinician support in CCBT can be provided by telephone, videoconference, and/or email, this highly efficient form of treatment could be a major advance in remote treatment delivery.
Venous Thromboembolism Complicated with COVID-19: What Do We Know So Far?
Authors: Tal Shir , Spectre Galia , Kornowski Ran , Perl Leor
Published: May 2020

Coronavirus disease (COVID-19) is caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and is responsible for the ongoing 2019–2020 pandemic. Venous thromboembolism (VTE), a frequent cardiovascular and/or respiratory complication among hospitalized patients, is one of the known sequelae of the illness. Hospitalized COVID-19 patients are often elderly, immobile, and show signs of coagulopathy. Therefore, it is reasonable to assume a high incidence of VTE among these patients. Presently, the incidence of VTE is estimated at around 25% of patients hospitalized in the intensive care unit for COVID-19 even under anticoagulant treatment at prophylactic doses. In this review, we discuss present knowledge of the topic, the unique challenges of diagnosis and treatment of VTE, as well as some of the potential mechanisms of increased risk for VTE during the illness. Understanding the true impact of VTE on patients with COVID-19 will potentially improve our ability to reach a timely diagnosis and initiate proper treatment, mitigating the risk for this susceptible population during a complicated disease.
Grãos detríticos de zircão do Grupo Itacolomi em sua área tipo, Quadrilátero Ferrífero, Minas Gerais: idades, proveniência e significado tectônico
Authors: Duque Tiago Rocha Faria , Alkmim Fernando Flecha , Lana Cristiano De Carvalho
Published: May 2020

O Grupo Itacolomi em sua localidade tipo, a serra homônima, situada na porção sudeste do Quadrilátero Ferrífero, Minas Gerais, caracteriza-se por uma sucessão de meta-arenitos, metaconglomerados e filitos. Nessa e demais ocorrências, o grupo é interpretado como uma associação de depósitos fluviais e de leques aluviais, acumulados em bacias intermontanas pós-orogênicas. As suas ocorrências na localidade tipo dão-se na forma de um bloco basal autóctone que jaz em discordância sobre rochas do Supergrupo Minas, e outro superior alóctone, lançado sobre o primeiro por uma falha de empurrão. O bloco autóctone corresponde à porção íntegra e internamente menos deformada do grupo e é constituído de um pacote de aproximadamente 400 m de meta-arenitos e metaconglomerados. No bloco alóctone, exposto no Pico do Itacolomi, meta-arenitos finos a médios com espessura de aproximadamente 145 m encontram-se, em geral, mais intensamente deformados. Os espectros de idades dos grãos de detríticos de zircão obtidos nos blocos autóctone e alóctone são ligeiramente diferentes. Os do primeiro são claramente unimodais, com picos em 2167, 2197 e 2203 Ma. Os do segundo são bimodais, com picos principais em 2156 e 2201 Ma. Eles indicam que as fontes principais do grupo devem ter sido, principalmente, os granitoides paleoproterozoicos do Cinturão Mineiro e do Complexo Mantiqueira, expostos respectivamente a sudoeste e leste da Serra do Itacolomi. A idade máxima de sedimentação do grupo pode ser estimada em 2129±11 Ma. Esses resultados, juntamente com outros disponíveis na literatura, indicam que o Grupo Itacolomi foi depositado em bacia de antepaís do orógeno paleoproterozoico que abarca o Quadrilátero Ferrífero e áreas adjacentes.
Metabolic Dysregulation of the Lysophospholipid/Autotaxin Axis in the Chromosome 9p21 Gene SNP rs10757274
Authors: Meckelmann Sven W. , Hawksworth Jade I. , White Daniel , Andrews Robert , Rodrigues Patricia , O’Connor Anne , Alvarez-Jarreta Jorge , Tyrrell Victoria J. , Hinz Christine , Zhou You , Williams Julie , Aldrovandi Maceler , Watkins William J. , Engler Adam J. , Lo Sardo Valentina , Slatter David A. , Allen Stuart M. , Acharya Jay , Mitchell Jacquie , Cooper Jackie , Aoki Junken , Kano Kuniyuki , Humphries Steve E. , O’Donnell Valerie B.
Published: May 2020

Background:

Common chromosome 9p21 single nucleotide polymorphisms (SNPs) increase coronary heart disease risk, independent of traditional lipid risk factors. However, lipids comprise large numbers of structurally related molecules not measured in traditional risk measurements, and many have inflammatory bioactivities. Here, we applied lipidomic and genomic approaches to 3 model systems to characterize lipid metabolic changes in common Chr9p21 SNPs, which confer ≈30% elevated coronary heart disease risk associated with altered expression of ANRIL, a long ncRNA.

Methods:

Untargeted and targeted lipidomics was applied to plasma from NPHSII (Northwick Park Heart Study II) homozygotes for AA or GG in rs10757274, followed by correlation and network analysis. To identify candidate genes, transcriptomic data from shRNA downregulation of ANRIL in HEK-293 cells was mined. Transcriptional data from vascular smooth muscle cells differentiated from induced pluripotent stem cells of individuals with/without Chr9p21 risk, nonrisk alleles, and corresponding knockout isogenic lines were next examined. Last, an in-silico analysis of miRNAs was conducted to identify how ANRIL might control lysoPL (lysophosphospholipid)/lysoPA (lysophosphatidic acid) genes.

Results:

Elevated risk GG correlated with reduced lysoPLs, lysoPA, and ATX (autotaxin). Five other risk SNPs did not show this phenotype. LysoPL-lysoPA interconversion was uncoupled from ATX in GG plasma, suggesting metabolic dysregulation. Significantly altered expression of several lysoPL/lysoPA metabolizing enzymes was found in HEK cells lacking ANRIL. In the vascular smooth muscle cells data set, the presence of risk alleles associated with altered expression of several lysoPL/lysoPA enzymes. Deletion of the risk locus reversed the expression of several lysoPL/lysoPA genes to nonrisk haplotype levels. Genes that were altered across both cell data sets were
DGKA, MBOAT2, PLPP1
, and
LPL.
The in-silico analysis identified 4 ANRIL-regulated miRNAs that control lysoPL genes as miR-186-3p, miR-34a-3p, miR-122-5p, and miR-34a-5p.

Conclusions:

A Chr9p21 risk SNP associates with complex alterations in immune-bioactive phospholipids and their metabolism. Lipid metabolites and genomic pathways associated with coronary heart disease pathogenesis in Chr9p21 and ANRIL-associated disease are demonstrated.
Association of an Acute Myocardial Infarction Readmission-Reduction Program With Mortality and Readmission
Authors: Wasfy Jason H. , Hidrue Michael K. , Ngo Jacqueline , Tanguturi Varsha K. , Cafiero-Fonseca Elizabeth T. , Thompson Ryan W. , Johnson Natalie , McDermott Susan T. , Singh Jagmeet P. , del Carmen Marcela G. , Ferris Timothy G.
Published: May 2020

Background:

Reducing hospital readmission after acute myocardial infarction (AMI) has the potential to both improve quality and reduce costs. As such, readmission after AMI has been a target of financial penalties through Medicare. However, substantial concern exists about potential adverse effects and efficacious readmission-reduction strategies are not well validated.

Methods and Results:

We started an AMI readmissions reduction program in November 2017. Between July 2016 and February 2019, hospital billing data were queried to detect all inpatient hospitalizations at the Massachusetts General Hospital for AMI. Thirty-day readmission was identified through hospital billing data, and mortality was extracted from our electronic health record. The data set was merged with claims data for patients in accountable care organizations to detect readmission at other hospitals. We performed segmented linear regression, adjusting for secular trend and case mix, to assess the independent association of our program on both outcome variables. After inclusion and exclusion criteria were applied, the study population included 2020 patients. The overall 30-day readmission rate was higher before the intervention than after the intervention (15.5% versus 10.7%,
P
=0.002). The overall 30-day mortality rate was similar in both time periods (1.8% versus 1.4%,
P
=0.457). The program was associated with initial reduction in 30-day readmission (−9.8%,
P
=0.0002) and 30-day mortality (−2.6%,
P
=0.041). The program did not change trend in 30-day readmission (+0.19% readmissions/mo,
P
=0.554) and trend in 30-day mortality (−0.21% deaths/mo,
P
=0.119).

Conclusions:

An AMI readmissions reduction program that increases outpatient and emergency department (ED) access to cardiology care is associated with reduced 30-day readmission and 30-day mortality. Similar statistical techniques can be used to conduct a rigorous, mechanistic program evaluation of other quality improvement initiatives.
Disparities and Impact of Medicaid Expansion on Left Ventricular Assist Device Implantation and Outcomes
Authors: Wang Xiaowen , Luke Alina A. , Vader Justin M. , Maddox Thomas M. , Joynt Maddox Karen E.
Published: May 2020

Background:

Left ventricular assist device (LVAD) therapy is an increasingly viable alternative for patients who are not candidates for heart transplantation or who are waiting for a suitable donor. We aimed to determine whether there is an association between sex, race/ethnicity, insurance coverage, and neighborhood income and access to/outcomes of LVAD implantation. We further analyzed whether access to LVAD improved in states that did versus did not expand Medicaid.

Methods and Results:

Retrospective cohort study using State Inpatient Databases to identify patients 18 to 85 years of age admitted for heart failure, cardiogenic shock, or LVAD implantation from 2012 to 2015. Logistic regression analyses adjusting for age, all the sociodemographic factors above, medical comorbidities, and a hospital random effect were used to quantify odds of receipt of LVADs, as well as outcomes conditional on receiving an LVAD, for the sociodemographic groups of interest. A total of 925 770 patients were included; 3972 (0.43%) received LVADs. After adjusting for age, comorbidities, and hospital effects, women (adjusted odds ratio [aOR], 0.45 [0.41–0.49]), black patients (aOR, 0.83 [0.74–0.92]), and Hispanic patients (aOR, 0.74 [0.64–0.87]) were less likely to receive LVADs than whites. Medicare (aOR, 0.79 [0.72–0.86]), Medicaid (aOR, 0.52 [0.46–0.58]), and uninsured patients (aOR, 0.17 [0.11–0.25]) were less likely to receive LVADs than the privately insured, and patients in low-income ZIP codes were less likely than those in higher income areas (aOR, 0.71 [0.65–0.77]). Among those who received LVADs, women (aOR, 1.78 [1.38–2.30]), patients of unknown race or race other than white, black, or Hispanic (aOR, 1.97 [1.42–2.74]), and uninsured patients (aOR, 4.86 [1.92–12.28]) had higher rates of in-hospital mortality. Medicaid expansion was not associated with an increase in LVAD implantation.

Conclusions:

There are meaningful sociodemographic disparities in access and outcomes for LVAD implantation. Medicaid expansion was not associated with an increase in LVAD rates.
Advancing Value-Based Models for Heart Failure
Authors: Joynt Maddox Karen , Bleser William K. , Crook Hannah L. , Nelson Adam J. , Hamilton Lopez Marianne , Saunders Robert S. , McClellan Mark B. , Brown Nancy ,   the American Heart Association Value-Based Models Learning Collaborative
Published: May 2020

Heart failure (HF) is a leading cause of hospitalizations and readmissions in the United States. Particularly among the elderly, its prevalence and costs continue to rise, making it a significant population health issue. Despite tremendous progress in improving HF care and examples of innovation in care redesign, the quality of HF care varies greatly across the country. One major challenge underpinning these issues is the current payment system, which is largely based on fee-for-service reimbursement, leads to uncoordinated, fragmented, and low-quality HF care. While the payment landscape is changing, with an increasing proportion of all healthcare dollars flowing through value-based payment models, no longitudinal models currently focus on chronic HF care. Episode-based payment models for HF hospitalization have yielded limited success and have little ability to prevent early chronic disease from progressing to later stages. The available literature suggests that primary care-based longitudinal payment models have indirectly improved HF care quality and cardiovascular care costs, but these models are not focused on addressing patients’ longitudinal chronic disease needs. This article describes the efforts and vision of the multi-stakeholder Value-Based Models Learning Collaborative of The Value in Healthcare Initiative, a collaboration of the American Heart Association and the Robert J. Margolis, MD, Center for Health Policy at Duke University. The Learning Collaborative developed a framework for a HF value-based payment model with a longitudinal focus on disease management (to reduce adverse clinical outcomes and disease progression among patients with stage C HF) and prevention (an optional track to prevent high-risk stage B pre-HF from progressing to stage C). The model is designed to be compatible with prevalent payment models and reforms being implemented today. Barriers to success and strategies for implementation to aid payers, regulators, clinicians, and others in developing a pilot are discussed.