bluuebunny/crossref_metadata_2025_split huggingface dataset:
DIRAS3, GPR171 and RAC2 were identified as the key molecular patterns associated with brain metastasis of breast cancer
Authors: Dai Ji , Chen Qi , Li Guoqing , Chen Mengze , Sun Haohang , Yan Meidi 
Published: September 2022

ObjectiveBrain metastasis is a primary cause of morbidity and mortality in breast cancer patients. Therefore, elucidation and understanding of the underlying mechanisms are essential for the development of new therapeutic strategies.MethodsDifferential gene analysis was performed for those with and without distant metastasis in The Cancer Genome Atlas (TCGA) database and those with and without recurrence in the brain in the dataset GSE12276. The differentially expressed genes procured from the two databases were intersected to obtain the intersecting genes associated with brain metastasis. Thereafter, the intersecting genes were subjected to LASSO model construction to screen for prognostic genes. The expression of the obtained genes in metastatic breast cancer was observed, and survival analysis was performed. Finally, GSEA analysis of the obtained genes was performed, and the relationship between them and immune cells was explored.ResultsA total of 335 differential genes for the occurrence of distant metastases were obtained based on the TCGA database. A total of 1070 differential genes for recurrence to the brain were obtained based on the dataset GSE12276. The Venn diagram showed 24 intersecting genes associated with brain metastasis. The LASSO prognostic model contained a total of five genes (GBP2, GPR171, DIRAS3, RAC2, and CACNA1D). Expression difference analysis showed that GBP2, GPR171, DIRAS3, and RAC2 were significantly down-regulated in expression in metastatic breast cancer compared with primary breast cancer tumors. Only GPR171, DIRAS3, and RAC2 were strongly correlated with the overall survival of breast cancer patients. Their correlation analysis with immune cells showed that the correlation coefficient between the expression levels of DIRAS3 and immune cells was low, and the expression levels of GPR171 and RAC2 were more closely correlated with B cells and macrophages.ConclusionsThe expression of DIRAS3, GPR171 and RAC2, genes associated with brain metastasis, was reduced in metastatic breast cancer, and GPR171 was found to promote brain metastasis of breast cancer cells by inducing B cells and thereby.
A review study of fetal circulatory models to develop a digital twin of a fetus in a perinatal life support system
Authors: van Willigen Bettine G. , van der Hout-van der Jagt M. Beatrijs , Huberts Wouter , van de Vosse Frans N. 
Published: September 2022

BackgroundPreterm birth is the main cause of neonatal deaths with increasing mortality and morbidity rates with decreasing GA at time of birth. Currently, premature infants are treated in neonatal intensive care units to support further development. However, the organs of, especially, extremely premature infants (born before 28 weeks of GA) are not mature enough to function optimally outside the womb. This is seen as the main cause of the high morbidity and mortality rates in this group. A liquid-filled incubator, a so-called PLS system, could potentially improve these numbers for extremely premature infants, since this system is designed to mimic the environment of the natural womb. To support the development and implementation of such a complex system and to interpret vital signals of the fetus during a PLS system operation, a digital twin is proposed. This mathematical model is connected with a manikin representing the digital and physical twin of the real-life PLS system. Before developing a digital twin of a fetus in a PLS system, its functional and technical requirements are defined and existing mathematical models are evaluated.Method and resultsThis review summarizes existing 0D and 1D fetal circulatory models that potentially could be (partly) adopted for integration in a digital twin of a fetus in a PLS system based on predefined requirements. The 0D models typically describe hemodynamics and/or oxygen transport during specific events, such as the transition from fetus to neonate. Furthermore, these models can be used to find hemodynamic differences between healthy and pathological physiological states. Rather than giving a global description of an entire cardiovascular system, some studies focus on specific organs or vessels. In order to analyze pressure and flow wave profiles in the cardiovascular system, transmission line or 1D models are used. As for now, these models do not include oxygen transport.ConclusionThis study shows that none of the models identified in literature meet all the requirements relevant for a digital twin of a fetus in a PLS system. Nevertheless, it does show the potential to develop this digital twin by integrating (parts) of models into a single model.
Automated identification of innocent Still's murmur using a convolutional neural network
Authors: Shekhar Raj , Vanama Ganesh , John Titus , Issac James , Arjoune Youness , Doroshow Robin W. 
Published: September 2022

BackgroundStill's murmur is the most prevalent innocent heart murmur of childhood. Auscultation is the primary clinical tool to identify this murmur as innocent. Whereas pediatric cardiologists routinely perform this task, primary care providers are less successful in distinguishing Still's murmur from the murmurs of true heart disease. This results in a large number of children with a Still's murmur being referred to pediatric cardiologists.ObjectivesTo develop a computer algorithm that can aid primary care providers to identify the innocent Still's murmur at the point of care, to substantially decrease over-referral.MethodsThe study included Still's murmurs, pathological murmurs, other innocent murmurs, and normal (i.e., non-murmur) heart sounds of 1,473 pediatric patients recorded using a commercial electronic stethoscope. The recordings with accompanying clinical diagnoses provided by a pediatric cardiologist were used to train and test the convolutional neural network-based algorithm.ResultsA comparative analysis showed that the algorithm using only the murmur sounds recorded at the lower left sternal border achieved the highest accuracy. The developed algorithm identified Still's murmur with 90.0% sensitivity and 98.3% specificity for the default decision threshold. The area under the receiver operating characteristic curve was 0.943.ConclusionsStill's murmur can be identified with high accuracy with the algorithm we developed. Using this approach, the algorithm could help to reduce the rate of unnecessary pediatric cardiologist referrals and use of echocardiography for a common benign finding.
Non-invasive estimation of QLV from the standard 12-lead ECG in patients with left bundle branch block
Authors: Melgaard Jacob , van Dam Peter M. , Sommer Anders , Fruelund Patricia , Nielsen Jens Cosedis , Riahi Sam , Graff Claus 
Published: September 2022

Background: Cardiac resynchronization therapy (CRT) is a treatment for patients with heart failure and electrical dyssynchrony, i.e., left bundle branch block (LBBB) ECG pattern. CRT resynchronizes ventricular contraction with a right ventricle (RV) and a left ventricle (LV) pacemaker lead. Positioning the LV lead in the latest electrically activated region (measured from Q wave onset in the ECG to LV sensing by the left pacemaker electrode [QLV]) is associated with favorable outcome. However, optimal LV lead placement is limited by coronary venous anatomy and the inability to measure QLV non-invasively before implantation. We propose a novel non-invasive method for estimating QLV in sinus-rhythm from the standard 12-lead ECG.Methods: We obtained 12-lead ECG, LV electrograms and LV lead position in a standard LV 17-segment model from procedural recordings from 135 standard CRT recipients. QLV duration was measured post-operatively. Using a generic heart geometry and corresponding forward model for ECG computation, the electrical activation pattern of the heart was fitted to best match the 12-lead ECG in an iterative optimization procedure. This procedure initialized six activation sites associated with the His-Purkinje system. The initial timing of each site was based on the directions of the vectorcardiogram (VCG). Timing and position of the sites were then changed iteratively to improve the match between simulated and measured ECG. Noninvasive estimation of QLV was done by calculating the time difference between Q-onset on the computed ECG and the activation time corresponding to centroidal epicardial activation time of the segment where the LV electrode is positioned. The estimated QLV was compared to the measured QLV. Further, the distance between the actual LV position and the estimated LV position was computed from the generic ventricular model.Results: On average there was no difference between QLV measured from procedural recordings and non-invasive estimation of QLV (ΔQLV=−3.0±22.5 ms, p=0.12). Median distance between actual LV pacing site and the estimated pacing site was 18.6 mm (IQR 17.3 mm).Conclusion: Using the standard 12-lead ECG and a generic heart model it is possible to accurately estimate QLV. This method may potentially be used to support patient selection, optimize implant procedures, and to simulate optimal stimulation parameters prior to pacemaker implantation.
Canadian aging and inactivity study: Spaceflight-inspired exercises during head-down tilt bedrest blunted reductions in muscle-pump but not cardiac baroreflex in older persons
Authors: Sadeghian Farshid , Divsalar Donya Naz , Fadil Rabie , Tavakolian Kouhyar , Blaber Andrew P. 
Published: September 2022

As part of the first Canadian aging and inactivity study (CAIS) we assessed the efficacy of space-based exercise countermeasures for maintenance of cardiac and muscle-pump baroreflex in older persons during bedrest. An initiative of the Canadian Space Agency, Canadian Institutes of Health Research and the Canadian Frailty Network, CAIS involved 14 days of 6-degree head-down tilt bedrest (HDBR) with (Exercise) or without (Control) combined upper and lower body strength, aerobic, and high-intensity interval training exercise countermeasures. Twenty healthy men and women aged 55 to 65, randomly divided into control and exercise groups (male control (MC, n = 5), male exercise (ME, n = 5), female control (FC, n = 6), female exercise (FE, n = 4)) (age: 58.7 ± 0.5 years, height: 1.67 ± 0.02 m, body mass: 70.2 ± 3.2 kg; mean ± SEM), completed the study. Cardiac and muscle-pump baroreflex activity were assessed with supine-to-stand tests. Wavelet transform coherence was used to characterise cardiac and muscle-pump baroreflex fraction time active (FTA) and gain values, and convergent cross-mapping was used to investigate causal directionality between blood pressure (BP) and heart rate, as well as BP and lower leg muscle electromyography (EMG). Seven of the twenty participants were unable to stand for 6 minutes after HDBR, with six of those being female. Our findings showed that 2 weeks of bedrest impaired skeletal muscle’s ability to return blood to the venous circulation differently across various sexes and intervention groups. Comparing values after bed rest with before bed rest values, there was a significant increase in heart rates (∆ of +25%; +17% in MC to +33% in FC; p &lt; 0.0001), beat-to-beat EMG decreased (∆ of −43%; −25% in ME to −58% in MC; p &lt; 0.02), while BP change was dependent on sex and intervention groups. Unlike their male counterparts, in terms of muscle-pump baroreflex, female participants had considerably decreased FTA after HDBR (p &lt; 0.01). All groups except female control demonstrated parallel decreases in cardiac active gain and causality, while the FC demonstrated an increase in cardiac causality despite a similar decline in cardiac active gain. Results showed that the proposed exercises may alleviate muscle-pump baroreflex declines but could not influence the cardiac baroreflex decline from 14 days of inactivity in older adults.
Early enzyme replacement therapy prevents dental and craniofacial abnormalities in a mouse model of mucopolysaccharidosis type VI
Authors: Nagpal Rohit , Georgi Gina , Knauth Sarah , Schmid-Herrmann Carmen , Muschol Nicole , Braulke Thomas , Kahl-Nieke Bärbel , Amling Michael , Schinke Thorsten , Koehne Till , Petersen Julian 
Published: September 2022

Mucopolysaccharidosis VI (MPS VI) is a hereditary lysosomal storage disease caused by the absence of the enzyme arylsulfatase B (ARSB). Craniofacial defects are common in MPS VI patients and manifest as abnormalities of the facial bones, teeth, and temporomandibular joints. Although enzyme replacement therapy (ERT) is the treatment of choice for MPS VI, the effects on the craniofacial and dental structures are still poorly understood. In this study, we used an Arsb-deficient mouse model (Arsbm/m) that mimics MPS VI to investigate the effects of ERT on dental and craniofacial structures and compared these results with clinical and radiological observations from three MPS VI patients. Using micro-computed tomography, we found that the craniofacial phenotype of the Arsbm/m mice was characterized by bone exostoses at the insertion points of the masseter muscles and an overall increased volume of the jaw bone. An early start of ERT (at 4 weeks of age for 20 weeks) resulted in a moderate improvement of these jaw anomalies, while a late start of ERT (at 12 weeks of age for 12 weeks) showed no effect on the craniofacial skeleton. While teeth typically developed in Arsbm/m mice, we observed a pronounced loss of tooth-bearing alveolar bone. This alveolar bone loss, which has not been described before in MPS VI, was also observed in one of the MPS VI patients. Interestingly, only an early start of ERT led to a complete normalization of the alveolar bone in Arsbm/m mice. The temporomandibular joints in Arsbm/m mice were deformed and had a porous articular surface. Histological analysis revealed a loss of physiological cartilage layering, which was also reflected in an altered proteoglycan content in the cartilage of Arsbm/m mice. These abnormalities could only be partially corrected by an early start of ERT. In conclusion, our results show that an early start of ERT in Arsbm/m mice achieves the best therapeutic effects for tooth, bone, and temporomandibular joint development. As the MPS VI mouse model in this study resembles the clinical findings in MPS VI patients, our results suggest enzyme replacement therapy should be started as early as possible.
Unfulfilled psychosocial needs of the adolescent siblings of patients with cancer and the identification of the related factors
Authors: Masoudifar Zeynab , Rassouli Maryam , Ashrafizadeh Hadis , Fathollah Zadeh Ensieh , Dadashi Nasrin , Khanali Mojen Leila 
Published: September 2022

BackgroundThe diagnosis of cancer in a child is a stressful experience for the entire family, particularly for adolescent or young adult siblings and their psychosocial needs (PSNs) may remain unfulfilled. The aim of the study was to assess the unfulfilled PSNs of the adolescent siblings of patients with cancer in Iran and examine the relationships between demographic and medical variables and PSNs.MethodsThis descriptive analytical study was conducted in 2019 in seven teaching hospitals in Tehran, Iran. Participants were 188 adolescent siblings of patients with cancer. Sampling was performed consecutively. Data were collected using a demographic and clinical characteristics questionnaire and the Sibling Cancer Needs Instrument (SCNI). To investigate the relationship between demographic variables and the mean score of PSNs subscales, first, the correlation was determined, and afterward, the significant variables were analyzed using multiple linear regression.ResultsIn total, 180 adolescent siblings completed the study. Their mean age was 15.66 ± 2.55 years and the mean summary score of their PSNs was 121.15 ± 32.73. Around 80.60% of adolescents indicated at least one unmet need related to each question. The most common unfulfilled needs of participants were related to the information about sibling’s cancer dimension (INFO) (mean: 2.94 ± 0.79) and the less common unfulfilled needs were related to the practical assistance dimension (UFAM) (mean: 2.38 ± 0.93). Based on the regression coefficients, a significant relationship was observed between the mean summary score of PSNs with the duration of cancer (β = –2.199, p = 0.006) and mother’s age (β = –2.805, p = 0.029).ConclusionThe adolescent siblings of patients with cancer have different unfulfilled PSNs, particularly respecting information about their siblings’ cancer and support for emotional coping. Family members and healthcare providers should provide these adolescents with strong informational support and fulfill their needs in order to promote their health and their emotional coping.
Prevalence and correlates of cannabis abuse among residents in the community of Fort McMurray, a city in Northern Alberta which had endured multiple natural disasters
Authors: Obuobi-Donkor Gloria , Eboreime Ejemai , Shalaby Reham , Agyapong Belinda , Agyapong Vincent I. O. 
Published: September 2022

BackgroundCannabis is one of the widely used drugs for relaxation and may be abuse among users. Researchers have given attention to cannabis use among the general population while vulnerable populations who have experience multiple traumas may be at risk of cannabis abuse. Other factors may influence cannabis abuse among people exposed to traumas.ObjectiveThe study aims to determine the prevalence and correlates of self-reported cannabis abuse among residents of Fort McMurray, a city in Northern Alberta, Canada.MethodsA cross-sectional survey was conducted using an online questionnaire. Sociodemographic data, trauma exposure, and clinical characteristics were collected to identify the possible risk factor of cannabis abuse. Data were analyzed with SPSS version 25 using a chi-square test and binary logistic regression analysis. Correlation analysis was also performed to ascertain likely cannabis abuse and the association with other mental health conditions.ResultsOverall, participants who completed the survey were one hundred and eighty-sixed out of the two hundred and forty-nine residents who accessed the online survey, giving a response rate of 74.7%. The prevalence of self-reported cannabis abuse among participants was 14%. Most of the participants were females (159, 85.5%), more than 40 years of age (98, 52.7%), employed (175, 94.1%), owned their house (145, 78.0%), and 103 (60.6%) reported being exposed to at least a trauma (COVID-19, flooding, or wildfire). Regarding regression analysis results, participants living in a rented accommodation were nearly four times more likely to abuse cannabis (OR = 3.86; 95% CI: 1.34–11.14) than those owning their houses. Similarly, male participants were more than 6-folds more likely to abuse cannabis than the female gender (OR= 6.25; 95% CI: 1.89–20), and participants in a relationship were six times more likely to abuse cannabis than participants not in a relationship (OR = 6.33; 95% CI: 1.67–24.39). The study also found significant association of depressive symptoms (X2 = 4.561; p = 0.033) and anxiety symptoms (X2 = 4.700; p = 0.030) with likely cannabis abuse.ConclusionDemographic factors significantly predicted likely cannabis abuse in the Fort McMurray population, and cannabis abuse significantly correlated with presence of moderate to high anxiety and depression symptoms. It is essential to mobilized resources to support vulnerable communities and manage cannabis abuse.
Development of a deep learning algorithm for myopic maculopathy classification based on OCT images using transfer learning
Authors: He Xiaoying , Ren Peifang , Lu Li , Tang Xuyuan , Wang Jun , Yang Zixuan , Han Wei 
Published: September 2022

PurposeTo apply deep learning (DL) techniques to develop an automatic intelligent classification system identifying the specific types of myopic maculopathy (MM) based on macular optical coherence tomography (OCT) images using transfer learning (TL).MethodIn this retrospective study, a total of 3,945 macular OCT images from 2,866 myopic patients were recruited from the ophthalmic outpatients of three hospitals. After culling out 545 images with poor quality, a dataset containing 3,400 macular OCT images was manually classified according to the ATN system, containing four types of MM with high OCT diagnostic values. Two DL classification algorithms were trained to identify the targeted lesion categories: Algorithm A was trained from scratch, and algorithm B using the TL approach initiated from the classification algorithm developed in our previous study. After comparing the training process, the algorithm with better performance was tested and validated. The performance of the classification algorithm in the test and validation sets was evaluated using metrics including sensitivity, specificity, accuracy, quadratic-weighted kappa score, and the area under the receiver operating characteristic curve (AUC). Moreover, the human-machine comparison was conducted. To better evaluate the algorithm and clarify the optimization direction, the dimensionality reduction analysis and heat map analysis were also used to visually analyze the algorithm.ResultsAlgorithm B showed better performance in the training process. In the test set, the algorithm B achieved relatively robust performance with macro AUC, accuracy, and quadratic-weighted kappa of 0.986, 96.04% (95% CI: 0.951, 0.969), and 0.940 (95% CI: 0.909–0.971), respectively. In the external validation set, the performance of algorithm B was slightly inferior to that in the test set. In human-machine comparison test, the algorithm indicators were inferior to the retinal specialists but were the same as the ordinary ophthalmologists. In addition, dimensionality reduction visualization and heatmap visualization analysis showed excellent performance of the algorithm.ConclusionOur macular OCT image classification algorithm developed using the TL approach exhibited excellent performance. The automatic diagnosis system for macular OCT images of MM based on DL showed potential application prospects.
Work climate in emergency health services during COVID-19 pandemic—An international multicenter study
Authors: Kosydar-Bochenek Justyna , Krupa Sabina , Religa Dorota , Friganovic Adriano , Oomen Ber , Williams Ged , Vollman Kathleen M. , Rogado Maria Isabelita C. , Goldsworthy Sandra , Lopez Violeta , Brioni Elena , Medrzycka-Dabrowska Wioletta 
Published: September 2022

IntroductionA good working climate increases the chances of adequate care. The employees of Emergency in Hospitals are particularly exposed to work-related stress. Support from management is very important in order to avoid stressful situations and conflicts that are not conducive to good work organization. The aim of the study was to assess the work climate of Emergency Health Services during COVID-19 Pandemic using the Abridged Version of the Work Climate Scale in Emergency Health Services.DesignA prospective descriptive international study was conducted.MethodsThe 24-item Abridged Version of the Work Climate Scale in Emergency Health Services was used for the study. The questionnaire was posted on the internet portal of scientific societies. In the study participated 217 women (74.5%) and 74 men (25.4%). The age of the respondents ranged from 23 to 60 years (SD = 8.62). Among the re-spondents, the largest group were Emergency technicians (85.57%), followed by nurses (9.62%), doctors (2.75%) and Service assistants (2.06%). The study was conducted in 14 countries.ResultsThe study of the climate at work shows that countries have different priorities at work, but not all of them. By answering the research questions one by one, we can say that the average climate score at work was 33.41 min 27.0 and max 36.0 (SD = 1.52).ConclusionThe working climate depends on many factors such as interpersonal relationships, remuneration or the will to achieve the same selector. In the absence of any of the elements, a proper working climate is not possible.