bluuebunny/crossref_metadata_2025 huggingface dataset:
Ductal Carcinoma In Situ of the Breast: Perspectives on Tumor Subtype and Treatment
Authors: Liu Yufei , Shou Kangquan , Li Juanjuan , Wu Qi , Hu Yuchang , Wang Junjie , Cao Chunyu , Wang Qing
Published: May 2020

Objective. To evaluate ductal carcinoma in situ (DCIS) characteristics and the effect of different treatment strategies. Patients and Methods. Using data with known hormone receptor (HoR) and human epidermal growth factor receptor 2 (HER2) status obtained by the Surveillance, Epidemiology, and End Results (SEER) program from 2010‐2014, the study was conducted to investigate tumor subtype‐specific differences in various characteristics, overall survival (OS), and breast cancer‐specific mortality (BCSM). Results. A total of 3415 patients with DCIS were eligible. Compared with HoR+/HER‐ subgroup, patients with triple‐negative (TN) and HoR‐/HER+ were commonly higher in grade, larger in size, and tended to receive mastectomy (P < 0.05). The multivariate analysis revealed that patients with TN were more likely to have a poorer OS and show a higher breast cancer‐specific mortality compared with the HoR+/HER‐ subgroup (P < 0.05). Multivariate analysis on the history of local treatment and surgery showed patients receiving breast‐conserving surgery (BCS) plus radiotherapy (R) and BCS plus axillary lymph node dissection was likely to improve OS without affecting breast cancer‐specific mortality (P < 0.05). Conclusion. The results demonstrate that DCIS associated with TN subtype portends poor prognosis. Meanwhile, BCS plus R was a preferable option and resulted in survival rates better than those achieved with mastectomy, and SLNB should be considered as an appropriate assessment of axillary staging in patients with DCIS.
Lipin-1 Deficiency-Associated Recurrent Rhabdomyolysis and Exercise-Induced Myalgia Persisting into Adulthood: A Case Report and Review of Literature
Authors: Indika Neluwa Liyanage Ruwan , Vidanapathirana Dinesha Maduri , Jasinge Eresha , Waduge Roshitha , Shyamali Narangoda Liyanage Ajantha , Perera Poruthotage Pradeep Rasika
Published: May 2020

Phosphatidate phosphatase-1 (lipin-1) is encoded by LPIN1 gene. Lipin-1 deficiency has been reported as the second most common cause of early-onset rhabdomyolysis after primary fatty acid oxidation disorders. We report a case of a 32-year-old Sri Lankan female with a history of more than 10 episodes of rhabdomyolysis and exercise intolerance since childhood. These episodes were triggered by infections and exercise. A temporal relationship between the acute episodes and use of drugs such as theophylline, mefenamic acid, co-trimoxazole, and combined oral contraceptive pills was also noted. There was marked elevation of serum creatine kinase and transaminases during acute episodes. Family history revealed parental consanguinity and an affected sibling who died of an acute episode associated with muscle weakness, dark coloured urine, and cyanosis, at the age of 2 years. The histochemical findings of the patient under discussion were consistent with a metabolic myopathy affecting membrane integrity. A homozygous, likely pathogenic variant c.1684G>T encoding p.(Glu562∗) was identified by clinical exome sequencing. Even though the studies to date give no convincing evidence of a possible causal or contributory relationship between the drugs under discussion and lipin-1 related rhabdomyolysis, this case highlights the importance of pharmacovigilance and reporting adverse drug reactions in patients with lipin-1 deficiency.
Experimental Investigation of the Influence for Stoping Sequence and Granular Grading on Lateral Pressure during the Nonpillar Sublevel Caving Mining
Authors: Liu Yang , He Rongxing , Ren Fengyu , Cao Jianli , Zhang Dongjie , Zhou Yanjun , Liu Huan , Li Guanghui , Zhang Jing
Published: May 2020

In this study, a self‐designed scaled physical model was conducted to investigate the variation laws of lateral pressure under different stoping sequences and granular gradings, and drawing ore in the experiments was used to simulate the mining process. Under the limiting equilibrium state, the values of lateral pressure increased exponentially with the increasing depth of granular media, and the growth rate of lateral pressure gradually decreased as the depth of granular media increased. Then, the laboratory results indicated that the distribution laws of lateral pressure were divided into three parts, namely, the drawing influencing region, the upper descending zone, and the central growth area. As the height of the isolated extraction zone (IEZ) increased, the scope of the drawing influencing region and the upper descending zone increased, while the range of central growth area decreased. In the case of an invariable height of IEZ, more reduction ratio and the scope for drawing influencing region could be appeared in the lower wall. Increasing the space between the drawpoints and granular grading were an effective way to control the reduction rate of lateral pressure in the drawing influencing region, while the scope of the above parts kept stable. Moreover, the average values of lateral pressure showed an increasing trend as the granular grading decreased at the same number of drawing ore.
Automatic Detection of the Aortic Annular Plane and Coronary Ostia from Multidetector Computed Tomography
Authors: Astudillo Patricio , Mortier Peter , Bosmans Johan , De Backer Ole , de Jaegere Peter , Iannaccone Francesco , De Beule Matthieu , Dambre Joni
Published: May 2020

Anatomic landmark detection is crucial during preoperative planning of transcatheter aortic valve implantation (TAVI) to select the proper device size and assess the risk of complications. The detection is currently a time-consuming manual process influenced by the image quality and subject to operator variability. In this work, we propose a novel automatic method to detect the relevant aortic landmarks from MDCT images using deep learning techniques. We trained three convolutional neural networks (CNNs) with 344 multidetector computed tomography (MDCT) acquisitions to detect five anatomical landmarks relevant for TAVI planning: the three basal attachment points of the aortic valve leaflets and the left and right coronary ostia. The detection strategy used these three CNN models to analyse a single MDCT image and yield three segmentation volumes as output. These segmentation volumes were averaged into one final segmentation volume, and the final predicted landmarks were obtained during a postprocessing step. Finally, we constructed the aortic annular plane, defined by the three predicted hinge points, and measured the distances from this plane to the predicted coronary ostia (i.e., coronary height). The methodology was validated on 100 patients. The automatic landmark detection was able to detect all the landmarks and showed high accuracy as the median distance between the ground truth and predictions is lower than the interobserver variations (1.5 mm [1.1–2.1], 2.0 mm [1.3–2.8] with a paired difference −0.5 ± 1.3 mm and p value <0.001). Furthermore, a high correlation is observed between predicted and manually measured coronary heights (for both R2 = 0.8). The image analysis time per patient was below one second. The proposed method is accurate, fast, and reproducible. Embedding this tool based on deep learning in the preoperative planning routine may have an impact in the TAVI environments by reducing the time and cost and improving accuracy.
Colorectal Neoplasia among Patients with and without Human Immunodeficiency Virus
Authors: Faqih Adil , Singal Amit G. , Fullington Hannah M. , Hewitt Benjamin , Burstein Ezra , Gopal Purva , Wylie Annika , Abrams John , Murphy Caitlin C.
Published: May 2020

Background:

Increasing availability of highly active antiretroviral therapy (HAART) for human immunodeficiency virus (HIV) has led to prolonged survival and rising incidence of non-HIV–defining cancers among patients with HIV. Compared with the general population, risk of colorectal cancer may differ among those with HIV due to immunosuppression, oncogenic viral coinfections, and higher prevalence of risk factors.

Methods:

We identified patients (age ≥50 years) diagnosed with HIV, prescribed HAART for ≥6 months, and receiving care in two large health care systems in Dallas, TX. Patients received a first colonoscopy between January 2009 and December 2017. We calculated a standardized prevalence ratio as the ratio of observed to expected number of advanced neoplasia (high-risk adenoma or colorectal cancer) using an age- and sex-matched cohort of patients without HIV (n = 10,250).

Results:

Among patients with HIV (n = 839), about two thirds (60.1%) had normal findings at colonoscopy; 6.8% had hyperplastic polyps only, 20.4% had low-risk adenomas, 11.7% had high-risk adenomas, and 1.1% had colorectal cancer. Prevalence of advanced neoplasia was similar between patients with and without HIV, with a standardized prevalence ratio of 0.99 (95% confidence interval, 0.81–1.19).

Conclusions:

There was no difference in the prevalence of colorectal neoplasia between patients with and without HIV.

Impact:

Patients with HIV appear to have similar risk of colorectal neoplasia compared to those without HIV and can therefore follow average-risk colorectal cancer screening guidelines.
Cytokine Blood Filtration Responses in COVID-19
Authors: AL Shareef Khaled , Bakouri Mohsen
Published: May 2020

The real issue with the COVID-19 pandemic is that a rapidly increasing number of patients with life-threatening complications are admitted in hospitals and are not well-administered. Although a limited number of patients use the intensive care unit (ICU), they consume medical resources, safety equipment, and enormous equipment with little possibility of rapid recovery and ICU discharge. This work reviews effective methods of using filtration devices in treatment to reduce the level of various inflammatory mediators and discharge patients from the ICU faster. Extracorporeal technologies have been reviewed as a medical approach to absorb cytokines. Although these devices do not kill or remove the virus, they are a promising solution for treating patients and their faster removal from the ICU, thus relieving the bottleneck.
Bronchiolitis als mögliche unerwünschte Wirkung von Immuncheckpoint-Inhibitoren
Authors: Kahn Nicolas Carlos
Published: May 2020

Immune checkpoint inhibitors (ICIs) have been shown to improve overall and progression-free survival in various cancers but have been associated with various immune-related adverse events (IRAEs), including interstitial lung disease, especially organizing pneumonia. We report 2 cases of isolated severe airway disease attributable to ICIs, a rarely reported pattern of lung toxicity. The first patient received nivolumab with or without ipilimumab in a randomized double-blind trial for locoregional metastatic melanoma. The second patient was treated with nivolumab for lung adenocarcinoma. An IRAE was suspected in both cases due to a temporal relationship between ICI initiation and symptom onset. ICIs were stopped, and high-dose prednisone, inhaled corticosteroids, and bronchodilators were administered, allowing a rapid clinical and functional improvement in Patient 1. In Patient 2, despite prolonged high-dose prednisone, only a stabilization of forced expiratory volume in 1 s could be achieved, and the disease course was complicated by respiratory infections resulting in further loss of lung function. The patient died 1 year later due to progression of metastatic disease. These 2 cases suggest that pulmonary IRAEs secondary to ICIs may present as isolated bronchitis or bronchiolitis, with variable outcomes following ICI withdrawal and systemic corticosteroids.
Catch Neuter Release and Pet Overpopulation Management in Southern Italy
Authors: Friz Dorothea
Published: May 2020

A stray dog problem is not necessarily due to animals not owned. In fact, it can be caused by owned dogs allowed to roam and reproduce freely around the whole territory. And if the authorities limit themselves to the policy of catching the dogs and keeping them in shelters, the problem will never be solved. Instead, the shelters will soon be very overcrowded, with tremendous animal welfare issues for the imprisoned animals and at a very high cost for the public. Spay/neuter and return projects will instead reduce the number of dogs in the territory and are an essential way of keeping constant control. This is what my experience in Southern Italy taught me.
Instructional Expertise and Micropolitics: The Social Networks of Instrumental Music Teachers
Authors: Shaw Ryan D.
Published: May 2020

The purpose of this study was to understand the social networks of three instrumental music teachers in a midwestern school district. Research questions were (1) How do instrumental music teachers describe their formal/instructional networks? and (2) How do instrumental music teachers’ social networks differ by career stage? I used a qualitative ego network design to map social networks of information sharing with a focus on the flow of social capital. Data sources included a name-generating questionnaire to construct networks and two semistructured interviews focusing on the nature and significance of teachers’ ties. Findings suggest that social networks showed particularities in terms of number of ties and tie strength. On matters of instruction, participants sought out music teachers whom they respected or who possessed specialized knowledge. Participants spoke of the importance of forging micropolitical ties to secure needs related to resources and scheduling, using ties strategically. Finally, participants felt that networks differed by career stage with advice seeking decreasing over time and networks becoming more close-knit. Implications are offered for music teachers and music teacher educators.
Teaching Physical Education in an Urban Intensive Environment
Authors: R. Richards K. Andrew , Hemphill Michael A. , Shiver Victoria N. , Gaudreault Karen Lux , Ramsey Victor
Published: May 2020

The purpose of this study was to understand the unique stressors faced by physical educators working in New York City schools. Participants included 34 New York City physical educators who participated in semi-structured interviews about their experiences teaching in an urban context. Qualitative data analysis resulted in the construction of four themes: (a) working with limited and inconsistent infrastructure, (b) navigating student diversity, (c) coping with marginalization and advocating for quality practices, and (d) managing the sociopolitics of teaching. These themes highlight the intersection between discipline and teaching context and are discussed through the lens of occupational socialization theory.
Repair of iatrogenic tracheal injury in acute respiratory failure with veno-venous extracorporeal membrane oxygenation
Authors: Go Pauline H , Pai Albert , Larson Sharon B , Parekh Kalpaj
Published: May 2020

Iatrogenic tracheal injuries are rare but potentially serious complications of endotracheal intubation that frequently require lung isolation to repair. This is not tolerated in patients with severe respiratory failure. We describe a case in a patient with acute respiratory distress syndrome, repaired using veno-venous extracorporeal membrane oxygenation.
Adverse Events, Functional Decline, and Access to Allied Health Therapies for Patients With Dementia During Acute Hospitalization
Authors: Fox Amanda , MacAndrew Margaret , Wyles Katy , Yelland Catherine , Beattie Elizabeth
Published: May 2020

The number of patients attending acute care hospitals with a diagnosis of dementia is increasing. The impact of hospitalization on function and adverse events is perceived to be greater for patients with dementia than those without. This study compared adverse events (falls, wounds, delirium, medication errors, infections, and incontinence), functional decline, and allied health therapy for patients with and without dementia ( n = 240). Patients with dementia experienced significantly more adverse events and constant observation by staff, were more dependent with mobility, hygiene and feeding, more often nil by mouth, confused, and incontinent. Patients with dementia were significantly more likely to receive speech and physiotherapy, although they did not significantly improve in function during their hospital stay. Conversely, patients without dementia significantly improved in mobility and continence. The unique health care needs of patients with dementia need to inform models of care, policy, and practice to support safe health care delivery in this vulnerable population.
Congenital Heart Disease in Patients With Cleft Lip/Palate and Its Impact on Cleft Management
Authors: Azadgoli Beina , Munabi Naikhoba C. O. , Fahradyan Artur , Auslander Allyn , McCullough Meghan , Aflatooni Nikki , Davidson Ward Sally L. , Kumar S. Ram , Sanchez-Lara Pedro A. , Swanson Jordan , Magee William P.
Published: May 2020

Objective:

To evaluate characteristics of congenital heart disease (CHD) in patients with cleft lip and/or palate (CL/P) and assess potential associations with cleft outcomes.

Design:

Retrospective review of all patients with CL/P who underwent primary cleft treatment from 2009 to 2015.

Setting:

Children’s Hospital Los Angeles, a tertiary hospital.

Patients:

Exclusion criteria included microform cleft lip diagnosis, international patients, and patients presenting for secondary repair or revision after primary repair at another institution.

Main Outcomes Measured:

Patient demographics, prenatal and birth characteristics, CL/P characteristics, syndromic status, postoperative complications, and other outcomes were analyzed relative to CHD diagnoses and management. Patients with CL/P with (+CHD) were compared to those without (−CHD) CHD using χ2 tests and analysis of variance.

Results:

Among 575 patients with CL/P, 83 (14.4%) had CHD. Congenital heart disease rates were significantly higher in patients with cleft palate (CP) compared to other cleft types (χ2, P = .009). Eighty-one (97.6%) out of 83 +CHD patients were diagnosed prior to initial CL/P surgical assessment. Twenty-three (27.7%) +CHD patients required surgical repair of 10 cardiac anomalies prior to cleft care. Congenital heart disease was associated with delayed CP repair and increased rates of fistula in isolated patients with CP.

Conclusions:

Congenital heart disease is known to be more prevalent in patients with CL/P. These data suggest the condition is particularly increased in patients with CP. Severe forms of CHD are diagnosed and treated prior to cleft care however postoperative fistula may be more common in patients with CHD. Therefore, careful attention is required for patient optimization and palatal flap dissection in patients with coexisting CHD and CL/P.
Science Communication Efforts and Identity at Popular Culture Conventions
Authors: James Vaughan
Published: May 2020

Informal science communication efforts play a large role in individuals’ science learning. The present study sought to examine a nontraditional science communication environment: popular culture conventions. Utilizing the communication theory of identity, identity was examined to determine how participants expressed their identities when interacting with science in the convention environment. Qualitative interviews were held with audience members ( n = 14) and science communicators ( n = 13). Interviews were thematically analyzed using the constant comparative method. Results suggest that audience members could experience changes in their identity, shifting their views so they thought of themselves as users, learners, and consumers of science.
Architected functionally graded porous lattice structures for optimized elastic-plastic behavior
Authors: Mahbod Mahshid , Asgari Masoud , Mittelstedt Christian
Published: May 2020

In this paper, the elastic–plastic mechanical properties of regular and functionally graded additively manufactured porous structures made by a double pyramid dodecahedron unit cell are investigated. The elastic moduli and also energy absorption are evaluated via finite element analysis. Experimental compression tests are performed which demonstrated the accuracy of numerical simulations. Next, single and multi-objective optimizations are performed in order to propose optimized structural designs. Surrogated models are developed for both elastic and plastic mechanical properties. The results show that elastic moduli and the plastic behavior of the lattice structures are considerably affected by the cell geometry and relative density of layers. Consequently, the optimization leads to a significantly better performance of both regular and functionally graded porous structures. The optimization of regular lattice structures leads to great improvement in both elastic and plastic properties. Specific energy absorption, maximum stress, and the elastic moduli in x- and y-directions are improved by 24%, 79%, 56%, and 9%, respectively, compared to the base model. In addition, in the functionally graded optimized models, specific energy absorption and normalized maximum stress are improved by 64% and 56%, respectively, in comparison with the base models.
Outsourced ciphertext-policy attribute-based encryption with partial policy hidden
Authors: Yu Jinxia , He Guanghui , Yan Xixi , Tang Yongli , Qin Rongxia
Published: May 2020

Attribute-based encryption is an efficient and flexible fine-grained access control scheme. However, how to realize the attribute privacy concerns in the access policy and optimize the heavy computing overhead have been not adequately addressed. First, in view of the open-access policies formulated by data owners in the cloud environment and the linear growth of bilinear pairing operations with the number of attributes in the decryption process, a verifiable outsourced attribute-based encryption with partial policy hidden scheme is proposed, in which the attribute name of access policy can be sent while attribute value involving sensitive information can be hidden, so nobody can infer information from the access policy. Second, the bilinear pairing operation and modular power operation are outsourced to the cloud server, then users only need to perform constant exponential operation to decrypt. In addition, the proposed scheme is based on the composite order bilinear group and satisfies full secure under the standard model. Finally, compared with other schemes in term of function and performance, it shows that this scheme is more efficient and suitable for resource-constrained mobile devices in outsourcing environment.
Determinants of national drug products acceptance across patients, pharmacists, and manufacturers: A mixed method study
Authors: Ahmed Kawther Khalid , Al-Jumaili Ali Azeez , Mutlak Shihab Hattab , Hadi Mohammed Kamel
Published: May 2020

Introduction

The national pharmaceutical industry is pivotal for both the health sector and the national economy. This study aims to identify determinants of national drug products acceptance. The objectives of this study were to quantitatively measure the level of patient and community pharmacist acceptance of national drug products available in community pharmacies and to qualitatively explore the barriers facing national pharmaceutical companies and investigate the suggested solutions.

Methods

This cross-sectional study used an explanatory mixed method design. It was conducted in Baghdad, Iraq from July through October 2018. The study included two surveys (one for pharmacy customers and another for pharmacists) and thereafter semi-structured interviews of national pharmaceutical company owners/managers. The interview guide was developed based on preliminary quantitative results. Thematic analysis was used to analyze the interview findings.

Results

We received 123 patient surveys and 125 usable pharmacist surveys. We conducted seven interviews and stopped when we reached saturation. Integrated qualitative and quantitative findings showed that the main determinants of national drug product acceptance are product characteristics (namely price, packaging, brand, and availability), healthcare providers effect on product promotion and perceived effectiveness, and regulations enforced by authorities mainly the Ministry of Health.

Conclusions

Product price was the number one modulating factor in patient decision-making when purchasing a drug product. It appears that physicians and pharmacists are playing negative or at least neutral role in promoting national drug products and sustaining patients trust in national drug products. Current policies appeared to slow national drug industry growth and limit manufacturers’ ability to expand their share in the market. Manufacturer marketing efforts can help in gaining physicians and pharmacists support of the national drug product. Reforms to current drug policy and regulations were proposed by manufacturers.
Killing the joy, feeling the cruelty: Feminist geographies of nationalism in Azerbaijan
Authors: Militz Elisabeth
Published: May 2020

Feminist political geographies complicate our understanding of nationalisms, unraveling the gendered, racist, sexualized and classed logics that enable and legitimize nationalist projects and experiences. Scholarship on the “national intimate” usefully re-centers those feminized and trivialized mundane practices, bodily experiences, subjects and spaces that in fact powerfully reproduce nationalist sentiments. I draw on this reframing here, demonstrating the insights of a feminist geographic critique of national enjoyment in Azerbaijan. In particular, I mobilize Sara Ahmed’s figure of the feminist “killjoy” to unmask how national enjoyment obscures and yet reproduces patriarchal, heterosexist and racist narratives and mundane bodily encounters. Examining national enjoyment around men’s football, women’s beauty, smoking and heterosexual marriage, I attend to the oft-ignored but vital embodied sites and objects involved in reproducing enjoyment in national meaning. I show the conditions that are necessary for different bodies to gain access to national enjoyment, and the emotional, bodily and economic investments that are necessary to navigate heteronormative, patriarchal and racialized alignments in enjoying the nation. Feminist, critical race and queer theory has unequivocally demonstrated that nationalisms depend on—indeed cannot be separated from—the workings of patriarchy, misogyny, racism and heterosexism. As geographers, moving forward, it is vital that we attend to this work if we are to better understand the ordinary power of national enjoyment.
The metabolic profiles of different fiber type populations under the emergence of the slow component of oxygen uptake
Authors: Conde Alonso Sonia , Gajanand Trishan , Ramos Joyce S. , Antonietti Jean-Philippe , Borrani Fabio
Published: May 2020

To investigate the influence of different metabolic muscle fiber profiles on the emergence of the slow component of oxygen uptake ($${\dot{\text{V}}\text{O}}_{2}$$V˙O2SC), 12 habitually active males completed four sessions of different combinations of work-to-work transition exercises up to severe intensity. Each transition was modeled to analyze the different kinetic parameters. Using a new approach, combining Henneman’s principle and superposition principle, a reconstructed kinetics was built by temporally aligning the start of each new transition and summing them. The primary phase time constant significantly slowed and the gain at the end (GainEnd) significantly increased when transitions started from a higher intensity (p < 0.001). Kinetic parameters from the reconstructed curve ($${\dot{\text{V}}\text{O}}_{2} {\text{baseline}}$$V˙O2baseline, time delay of primary phase, $${\dot{\text{V}}\text{O}}_{2}$$V˙O2End and GainEnd) were not significantly different from one transition to severe exercise. These results suggest that the appearance of the $${\dot{\text{V}}\text{O}}_{2}$$V˙O2SC is at least related to, if not the result of, the different metabolic properties of muscle fibers.
Effect of baseline cognitive impairment on association between predicted propofol effect site concentration and Bispectral index or sedation score
Authors: Sieber Frederick , Neufeld Karin , Oh Esther S. , Gottschalk Allan , Wang Nae-Yuh
Published: May 2020

Background

This study determined whether the relationship between predicted propofol effect site concentration (Ce) and observer’s assessment of alertness/sedation scale (OAA/S) or Bispectral Index (BIS) was similar comparing cognitively intact vs impaired patients undergoing hip fracture repair with spinal anesthesia and sedation.

Methods

Following informed consent baseline mini-mental status exam (MMSE), Clinical Dementia Rating (CDR) and geriatric depression scale (GDS) were obtained. Intraoperatively OAA/S, BIS, and propofol (timing and exact amounts) administered were recorded. Cerebrospinal fluid was collected for Alzheimer’s (AD) biomarkers. Mean Ce level (AvgCe) during surgery was calculated using the area under the Ce measurement series from incision to closure, divided by surgical time. Average OAA/S (AvgOAA/S), and BIS (AvgBIS) were similarly calculated. Pearson correlations of AvgCe with AvgOAA/S and AvgBIS were calculated overall and by CDR. Nonparametric locally weighted scatterplot smoothing (LOWESS) fits of AvgOAA/S and AvgBIS on AvgCe were produced, stratified by CDR. Multivariable regression incorporating baseline cognitive measurements or AD biomarkers assessed AvgOAA/S or AvgBIS associations with AvgCe.

Results

In 186 participants AvgBIS and AvgOAA/S correlated with AvgCe (Pearson ρ = − 0.72; p < 0.0001 and Pearson ρ = − 0.81; p < 0.0001, respectively), and remained unchanged across CDR levels. Association patterns of AvgOAA/S or AvgBIS on AvgCe guided by LOWESS fits and modeled through regression, were similar when stratified by CDR (p = 0.16). Multivariable modeling found no independent effect on AvgBIS or AvgOAA/S by MMSE, CDR, GDS, or AD biomarkers after accounting for AvgCe.

Conclusions

When administering sedation in conjunction with spinal anesthesia, cognitive impairment does not affect the relationship between predicted propofol AvgCe and AvgOAA/S or AvgBIS.
A typology of useful evidence: approaches to increase the practical value of intervention research
Authors: Hasson Henna , Leviton Laura , von Thiele Schwarz Ulrica
Published: May 2020

Background

Too often, studies of evidence-based interventions (EBIs) in preventive, community, and health care are not sufficiently useful to end users (typically practitioners, patients, policymakers, or other researchers). The ways in which intervention studies are conventionally conducted and reported mean that there is often a shortage of information when an EBI is used in practice.

The paper aims to invite the research community to consider ways to optimize not only the trustworthiness but also the research’s usefulness in intervention studies. This is done by proposing a typology that provides some approaches to useful EBIs for intervention researchers. The approaches originate from different research fields and are summarized to highlight their potential benefits from a usefulness perspective.

Main message

The typology consists of research approaches to increase the usefulness of EBIs by improving the reporting of four features in intervention studies: (1) the interventions themselves, including core components and appropriate adaptations; (2) strategies to support–high-quality implementation of the interventions; (3) generalizations about the evidence in a variety of contexts; and (4) outcomes based on end users’ preferences and knowledge. The research approaches fall into three levels: Description, Analysis, and Design. The first level, Description, outlines what types of information about the intervention and its implementation, context, and outcomes can be helpful for end users. Research approaches under analysis offers alternative ways of analyzing data, increasing the precision of information provided to end users. Approaches summarized under design involve more radical changes and far-reaching implications for how research can provide more useful information. These approaches partly flip the order of efficacy and effectiveness, focusing not on whether an intervention works in highly controlled and optimal circumstances, but first and foremost whether an intervention can be implemented and lead to anticipated outcomes in everyday practice.

Conclusions

The research community, as well as the end users of research, are invited to consider ways to optimize research’s usefulness as well as its trustworthiness. Many of the research approaches in the typology are not new, and their contributions to quality have been described for generations – but their contributions to useful knowledge need more attention.
Docosahexaenoic acid in ARSACS: observations in two patients
Authors: Ricca Ivana , Tessa Alessandra , Trovato Rosanna , Bacci Giacomo Maria , Santorelli Filippo Maria
Published: May 2020

Background

Spastic ataxia of Charlevoix-Saguenay is a neurodegenerative condition due to mutations in the SACS gene and without a cure. Attempts to treatments are scarce and limited to symptomatic drugs.

Case presentation

Two siblings harboring biallelic variants in SACS underwent oral supplementation (600 mg/die) with docosahexaenoic acid (DHA), a well-tolerated dietary supplement currently used in SCA38 patients. We assessed over a 20 month-period clinical progression using disease-specific rating scales.

Conclusions

DHA was safe over a long period and well-tolerated by the two patients; both showed a stabilization of clinical symptoms, rather than the expected deterioration, warranting additional investigations in patients with mutations in SACS.
Diacylglycerol-evoked activation of PKC and PKD isoforms in regulation of glucose and lipid metabolism: a review
Authors: Kolczynska Katarzyna , Loza-Valdes Angel , Hawro Izabela , Sumara Grzegorz
Published: May 2020

Protein kinase C (PKC) and Protein kinase D (PKD) isoforms can sense diacylglycerol (DAG) generated in the different cellular compartments in various physiological processes. DAG accumulates in multiple organs of the obese subjects, which leads to the disruption of metabolic homeostasis and the development of diabetes as well as associated diseases. Multiple studies proved that aberrant activation of PKCs and PKDs contributes to the development of metabolic diseases. DAG-sensing PKC and PKD isoforms play a crucial role in the regulation of metabolic homeostasis and therefore might serve as targets for the treatment of metabolic disorders such as obesity and diabetes.
Incremental prognostic value of echocardiography of left ventricular remodeling and diastolic function in STICH trial
Authors: Kim Kyung-Hee , She Lilin , Lee Kerry L. , Dabrowski Rafal , Grayburn Paul A. , Rajda Miroslaw , Prior David L. , Desvigne-Nickens Patrice , Zoghbi William A. , Senni Michele , Stefanelli Guglielmo , Beghi Cesare , Huynh Thao , Velazquez Eric J. , Oh Jae K. , Lin Grace
Published: May 2020

Aims

We sought to determine which echocardiographic markers of left ventricular (LV) remodeling and diastolic dysfunction can contribute as incremental and independent prognostic information in addition to current clinical risk markers of ischemic LV systolic dysfunction in the Surgical Treatment for Ischemic Heart Failure (STICH) trial.

Methods and results

The cohort consisted of 1511 of 2136 patients in STICH for whom baseline transmitral Doppler (E/A ratio) could be measured by an echocardiographic core laboratory blinded to treatment and outcomes, and prognostic value of echocardiographic variables was determined by a Cox regression model. E/A ratio was the most significant predictor of mortality amongst diastolic variables with lowest mortality for E/A closest 0.8, although mortality was consistently low for E/A 0.6 to 1.0. Mortality increased for E/A < 0.6 and > 1.0 up to approximately 2.3, beyond which there was no further increase in risk. Larger LV end-systolic volume index (LVESVI) and E/A < 0.6 and > 1.0 had incremental negative effects on mortality when added to a clinical multivariable model, where creatinine, LVESVI, age, and E/A ratio accounted for 74% of the prognostic information for predicting risk. LVESVI and E/A ratio were stronger predictors of prognosis than New York Heart Association functional class, anemia, diabetes, history of atrial fibrillation, and stroke.

Conclusions

Echocardiographic markers of advanced LV remodeling and diastolic dysfunction added incremental prognostic value to current clinical risk markers. LVESVI and E/A ratio outperformed other markers and should be considered as standard in assessing risks in ischemic heart failure. E/A closest to 0.8 was the most optimal filling pattern.
Low doses of Bisphenol S affect post-translational modifications of sperm proteins in male mice
Authors: Řimnáčová Hedvika , Štiavnická Miriam , Moravec Jiří , Chemek Marouane , Kolinko Yaroslav , García-Álvarez Olga , Mouton Peter R. , Trejo Azalia Mariel Carranza , Fenclová Tereza , Eretová Nikola , Hošek Petr , Klein Pavel , Králíčková Milena , Petr Jaroslav , Nevoral Jan
Published: May 2020

Background

Bisphenol S (BPS) is increasingly used as a replacement for bisphenol A in the manufacture of products containing polycarbonates and epoxy resins. However, further studies of BPS exposure are needed for the assessment of health risks to humans. In this study we assessed the potential harmfulness of low-dose BPS on reproduction in male mice.

Methods

To simulate human exposure under experimental conditions, 8-week-old outbred ICR male mice received 8 weeks of drinking water containing a broad range of BPS doses [0.001, 1.0, or 100 μg/kg body weight (bw)/day, BPS1–3] or vehicle control. Mice were sacrificed and testicular tissue taken for histological analysis and protein identification by nano-liquid chromatography/mass spectrometry (MS) and sperm collected for immunodetection of acetylated lysine and phosphorylated tyrosine followed by protein characterisation using matrix-assisted laser desorption ionisation time-of-flight MS (MALDI-TOF MS).

Results

The results indicate that compared to vehicle, 100 μg/kg/day exposure (BPS3) leads to 1) significant histopathology in testicular tissue; and, 2) higher levels of the histone protein γH2AX, a reliable marker of DNA damage. There were fewer mature spermatozoa in the germ layer in the experimental group treated with 1 μg/kg bw (BPS2). Finally, western blot and MALDI-TOF MS studies showed significant alterations in the sperm acetylome and phosphorylome in mice treated with the lowest exposure (0.001 μg/kg/day; BPS1), although the dose is several times lower than what has been published so far.

Conclusions

In summary, this range of qualitative and quantitative findings in young male mice raise the possibility that very low doses of BPS may impair mammalian reproduction through epigenetic modifications of sperm proteins.
A novel NGS-based microsatellite instability (MSI) status classifier with 9 loci for colorectal cancer patients
Authors: Zheng Kai , Wan Hua , Zhang Jie , Shan Guangyu , Chai Ningning , Li Dongdong , Fang Nan , Liu Lina , Zhang Jingbo , Du Rong , Wu Qixi , Li Xichuan , Zhang Chunze
Published: May 2020

Background

With the recent emergence of immune checkpoint inhibitors, microsatellite instability (MSI) status has become an important biomarker for immune checkpoint blockade therapy. There are growing technical demands for the integration of different genomic alterations profiling including MSI analysis in a single assay for full use of the limited tissues.

Methods

Tumor and paired control samples from 64 patients with primary colorectal cancer were enrolled in this study, including 14 MSI-high (MSI-H) cases and 50 microsatellite stable (MSS) cases determined by MSI-PCR. All the samples were sequenced by a customized NGS panel covering 2.2 MB. A training dataset of 28 samples was used for selection of microsatellite loci and a novel NGS-based MSI status classifier, USCI-msi, was developed. NGS-based MSI status, single nucleotide variant (SNV) and tumor mutation burden (TMB) were detected for all patients. Most of the patients were also independently detected by immunohistochemistry (IHC) staining.

Results

A 9-loci model for detecting microsatellite instability was able to correctly predict MSI status with 100% sensitivity and specificity compared with MSI-PCR, and 84.3% overall concordance with IHC staining. Mutations in cancer driver genes (APC, TP53, and KRAS) were dispersed in MSI-H and MSS cases, while BRAF p.V600E and frameshifts in TCF7L2 gene occurred only in MSI-H cases. Mismatch repair (MMR)-related genes are highly mutated in MSI-H samples.

Conclusion

We established a new NGS-based MSI classifier, USCI-msi, with as few as 9 microsatellite loci for detecting MSI status in CRC cases. This approach possesses 100% sensitivity and specificity, and performed robustly in samples with low tumor purity.
Lipopolysaccharide-induced changes in the neurovascular unit in the preterm fetal sheep brain
Authors: Disdier Clémence , Awa Fares , Chen Xiaodi , Dhillon Simerdeep K. , Galinsky Robert , Davidson Joanne O. , Lear Christopher A. , Bennet Laura , Gunn Alistair J. , Stonestreet Barbara S.
Published: May 2020

Background

Exposure to inflammation during pregnancy can predispose to brain injury in premature infants. In the present study, we investigated the effects of prolonged exposure to inflammation on the cerebrovasculature of preterm fetal sheep.

Methods

Chronically instrumented fetal sheep at 103–104 days of gestation (full term is ~ 147 days) received continuous low-dose lipopolysaccharide (LPS) infusions (100 ng/kg over 24 h, followed by 250 ng/kg/24 h for 96 h plus boluses of 1 μg LPS at 48, 72, and 96 h) or the same volume of normal saline (0.9%, w/v). Ten days after the start of LPS exposure at 113–114 days of gestation, the sheep were killed, and the fetal brain perfused with formalin in situ. Vessel density, pericyte and astrocyte coverage of the blood vessels, and astrogliosis in the cerebral cortex and white matter were determined using immunohistochemistry.

Results

LPS exposure reduced (P < 0.05) microvascular vessel density and pericyte vascular coverage in the cerebral cortex and white matter of preterm fetal sheep, and increased the activation of perivascular astrocytes, but decreased astrocytic vessel coverage in the white matter.

Conclusions

Prolonged exposure to LPS in preterm fetal sheep resulted in decreased vessel density and neurovascular remodeling, suggesting that chronic inflammation adversely affects the neurovascular unit and, therefore, could contribute to long-term impairment of brain development.
Mental health and psychosocial well-being during the COVID-19 pandemic: the invisible elephant in the room
Authors: Otu Akaninyene , Charles Carlo Handy , Yaya Sanni
Published: May 2020

The novel SARS-CoV-2 coronavirus pandemic has emerged as a truly formidable threat to humankind’s existence. In the wake of the massively volatile global situation created by COVID-19, it is vital to recognize that the trauma it causes can affect people in different ways, at the individual and collective levels, resulting in mental health challenges for many. Although mental health problems account for about one-third of the world’s disability among adults, these issues tend to be under-addressed and overlooked in society and are closely associated with deadly disease outbreaks. In large scale outbreaks, the mental health problems experienced are not limited to infected persons but also extend to involve frontline health workers and community members alike. While it is crucial to limit the spread of infections during an outbreak, previous experience suggests that mental and behavioural health interventions should be fully included in public health response strategies.
Long non-coding RNA LINC00520 promotes the proliferation and metastasis of malignant melanoma by inducing the miR-125b-5p/EIF5A2 axis
Authors: Luan Wenkang , Ding Yuting , Yuan Haitao , Ma Shaojun , Ruan Hongru , Wang Jinlong , Lu Feng , Bu Xuefeng
Published: May 2020

Background

Long intergenic non-protein coding RNA 520 (LINC00520), a novel identified lncRNA, has been shown to modulate the malignant phenotype of tumor cells in some malignant tumors. However, the exact role and molecular mechanism of LINC00520 in malignant melanoma has not been studied.

Methods

The expression of LINC00520 in melanoma tissues were detected by using RNA-seq analysis and qRT-PCR. Melanoma cases from the public databases (The Cancer Genome Atlas (TCGA), GEO#GSE15605, GEO#GSE34460 and GEO#GSE24996) were included in this study. CCK-8 assay, EdU assay, transwell and scratch wound assay were used to explore the role of LINC00520 in melanoma cells. Luciferase reporter assays, MS2-RIP, RNA pull-down and RNA-ChIP assay were used to demonstrate the molecular biological mechanism of LINC00520 in melanoma.

Results

We found that LICN00520 was found to be overexpressed in melanoma tissue. High expression of LICN00520 is a risk factor for the prognosis of melanoma patients. LINC00520 promotes the proliferation, invasion and migration of melanoma cells. LICN00520 exerted its oncogenic role by competitive binding miR-125b-5p to promote Eukaryotic initiation factor 5A2 (EIF5A2) expression. We also showed that LICN00520 promotes the growth and metastasis of melanoma in vivo through regulating miR-125b-5p/EIF5A2 axis.

Conclusions

All results elucidated the role and molecular mechanism of LINC00520 in the malignant development of melanoma. LINC00520, a new oncogene in melanoma, maybe serve as a survival biomarkers or therapeutic target for melanoma patients.
Risk of early progression according to circulating ESR1 mutation, CA-15.3 and cfDNA increases under first-line anti-aromatase treatment in metastatic breast cancer
Authors: Clatot Florian , Perdrix Anne , Beaussire Ludivine , Lequesne Justine , Lévy Christelle , Emile George , Bubenheim Michael , Lacaille Sigrid , Calbrix Céline , Augusto Laetitia , Guillemet Cécile , Alexandru Cristina , Fontanilles Maxime , Sefrioui David , Burel Lucie , Guénot Sabine , Richard Doriane , Sarafan-Vasseur Nasrin , Di Fiore Frédéric
Published: May 2020

Background

Endocrine therapy is recommended as a first-line treatment for hormone receptor-positive metastatic breast cancer (HR+MBC) patients. No biomarker has been validated to predict tumor progression in that setting. We aimed to prospectively compare the risk of early progression according to circulating ESR1 mutations, CA-15.3, and circulating cell-free DNA in MBC patients treated with a first-line aromatase inhibitor (AI).

Methods

Patients with MBC treated with a first-line AI were prospectively included. Circulating biomarker assessment was performed every 3 months. The primary objective was to determine the risk of progression or death at the next follow-up visit (after 3 months) in case of circulating ESR1 mutation detection among patients treated with a first-line AI for HR+MBC.

Results

Overall, 103 patients were included, and 70 (68%) had progressive disease (PD). Circulating ESR1 mutations were detected in 22/70 patients with PD and in 0/33 patients without progression (p < 0.001). Among the ESR1-mutated patients, 18/22 had a detectable mutation prior to progression, with a median delay of 110 days from first detection to PD. The detection of circulating ESR1 mutations was associated with a 4.9-fold (95% CI 3.0–8.0) increase in the risk of PD at 3 months. Using a threshold value of 25% or 100%, a CA-15.3 increase was also correlated with progression (p < 0.001 and p = 0.003, respectively). In contrast to ESR1, the CA-15.3 increase occurred concomitantly with PD in most cases, in 27/47 (57%) with a 25% threshold and in 21/25 (84%) with a 100% threshold. Using a threshold value of either 25% or 100%, cfDNA increase was not correlated with progression.

Conclusion

The emergence of circulating ESR1 mutations is associated with a 4.9-fold increase in the risk of early PD during AI treatment in HR+MBC. Our results also highlighted that tracking circulating ESR1 mutations is more relevant than tracking CA-15.3 or cfDNA increase to predict progression in this setting.

Trial registration

ClinicalTrials.gov, NCT02473120. Registered 16 June 2015—retrospectively registered after one inclusion (first inclusion 1 June 2015)