bluuebunny/crossref_metadata_2025_split huggingface dataset:
Tens of images can suffice to train neural networks for malignant leukocyte detection
Authors: Schouten Jens P. E. , Matek Christian , Jacobs Luuk F. P. , Buck Michèle C. , Bošnački Dragan , Marr Carsten 
Published: April 2021

AbstractConvolutional neural networks (CNNs) excel as powerful tools for biomedical image classification. It is commonly assumed that training CNNs requires large amounts of annotated data. This is a bottleneck in many medical applications where annotation relies on expert knowledge. Here, we analyze the binary classification performance of a CNN on two independent cytomorphology datasets as a function of training set size. Specifically, we train a sequential model to discriminate non-malignant leukocytes from blast cells, whose appearance in the peripheral blood is a hallmark of leukemia. We systematically vary training set size, finding that tens of training images suffice for a binary classification with an ROC-AUC over 90%. Saliency maps and layer-wise relevance propagation visualizations suggest that the network learns to increasingly focus on nuclear structures of leukocytes as the number of training images is increased. A low dimensional tSNE representation reveals that while the two classes are separated already for a few training images, the distinction between the classes becomes clearer when more training images are used. To evaluate the performance in a multi-class problem, we annotated single-cell images from a acute lymphoblastic leukemia dataset into six different hematopoietic classes. Multi-class prediction suggests that also here few single-cell images suffice if differences between morphological classes are large enough. The incorporation of deep learning algorithms into clinical practice has the potential to reduce variability and cost, democratize usage of expertise, and allow for early detection of disease onset and relapse. Our approach evaluates the performance of a deep learning based cytology classifier with respect to size and complexity of the training data and the classification task.
The kebab technique uses a bipolar pencil to retrieve a dropped nucleus of the lens via a small incision
Authors: Aso Hiroshi , Yokota Harumasa , Hanazaki Hirotsugu , Yamagami Satoru , Nagaoka Taiji 
Published: April 2021

AbstractWe developed a new method to retrieve a dropped nucleus of the lens via a small incision using bipolar pencils, the kebab technique, to solve the lack of small-gauge fragmatomes, and the expense and toxicity of perfluorocarbon liquids (PFCL). A total of 8 eyes in 6 patients underwent this technique and were reviewed. After vitrectomy, the dropped nucleus of the lens was lifted from the retina by adhesion with a bipolar pencil, and phacoemulsification was performed while rotating the lens. The outcome measures were best-corrected visual acuity (BCVA), intraocular pressure (IOP), and corneal endothelial cell density before and after surgery. Surgical indications included zonular weakness, trauma, acute angle closure attack, and phacolytic glaucoma. At 1 month, BCVA improved from a mean (standard deviation, SD) 1.67 logMAR (0.90) to 1.14 logMAR (1.01). The mean preoperative IOP was 24.5 (16.8) mmHg and postoperative IOP was 11.0 (2.8) mmHg. The mean preoperative corneal endothelial cell count was 2600 (322) cells/mm2 (one eye was unmeasurable) and postoperative corneal endothelial cell count was 2387 (431) cells/mm2. There were no postoperative complications. The retrieval of a dropped nucleus of the lens using a bipolar pencil enables small incisions without using PFCL.
Sustained high expression of multiple APOBEC3 cytidine deaminases in systemic lupus erythematosus
Authors: Perez-Bercoff Danielle , Laude Hélène , Lemaire Morgane , Hunewald Oliver , Thiers Valérie , Vignuzzi Marco , Blanc Hervé , Poli Aurélie , Amoura Zahir , Caval Vincent , Suspène Rodolphe , Hafezi François , Mathian Alexis , Vartanian Jean-Pierre , Wain-Hobson Simon 
Published: April 2021

AbstractAPOBEC3 (A3) enzymes are best known for their role as antiviral restriction factors and as mutagens in cancer. Although four of them, A3A, A3B, A3F and A3G, are induced by type-1-interferon (IFN-I), their role in inflammatory conditions is unknown. We thus investigated the expression of A3, and particularly A3A and A3B because of their ability to edit cellular DNA, in Systemic Lupus Erythematosus (SLE), a chronic inflammatory disease characterized by high IFN-α serum levels. In a cohort of 57 SLE patients, A3A and A3B, but also A3C and A3G, were upregulated ~ 10 to 15-fold (> 1000-fold for A3B) compared to healthy controls, particularly in patients with flares and elevated serum IFN-α levels. Hydroxychloroquine, corticosteroids and immunosuppressive treatment did not reverse A3 levels. The A3AΔ3B polymorphism, which potentiates A3A, was detected in 14.9% of patients and in 10% of controls, and was associated with higher A3A mRNA expression. A3A and A3B mRNA levels, but not A3C or A3G, were correlated positively with dsDNA breaks and negatively with lymphopenia. Exposure of SLE PBMCs to IFN-α in culture induced massive and sustained A3A levels by 4 h and led to massive cell death. Furthermore, the rs2853669 A > G polymorphism in the telomerase reverse transcriptase (TERT) promoter, which disrupts an Ets-TCF-binding site and influences certain cancers, was highly prevalent in SLE patients, possibly contributing to lymphopenia. Taken together, these findings suggest that high baseline A3A and A3B levels may contribute to cell frailty, lymphopenia and to the generation of neoantigens in SLE patients. Targeting A3 expression could be a strategy to reverse cell death and the generation of neoantigens.
Machine learning reveals that structural features distinguishing promiscuous and non-promiscuous compounds depend on target combinations
Authors: Feldmann Christian , Bajorath Jürgen 
Published: April 2021

AbstractCompounds with defined multi-target activity (promiscuity) play an increasingly important role in drug discovery. However, the molecular basis of multi-target activity is currently only little understood. In particular, it remains unclear whether structural features exist that generally characterize promiscuous compounds and set them apart from compounds with single-target activity. We have devised a test system using machine learning to systematically examine structural features that might characterize compounds with multi-target activity. Using this system, more than 860,000 diagnostic predictions were carried out. The analysis provided compelling evidence for the presence of structural characteristics of promiscuous compounds that were dependent on given target combinations, but not generalizable. Feature weighting and mapping identified characteristic substructures in test compounds. Taken together, these findings are relevant for the design of compounds with desired multi-target activity.
Decreased choroidal and scleral thicknesses in highly myopic eyes with posterior staphyloma
Authors: Park Un Chul , Lee Eun Kyoung , Kim Bo Hee , Oh Baek-Lok 
Published: April 2021

AbstractIn this cross-sectional study, we investigated choroidal thickness (CT) and scleral thickness (ST) in highly myopic eyes and their associations with ocular factors. Patients underwent widefield swept-source optical coherence tomography (OCT) to measure the CT and ST at the subfovea and 3000 μm superior, inferior, temporal, and nasal to the fovea and macular curvature. A total of 237 eyes (154 patients) were included. At all five measurement points, thinner CTs and STs were associated with longer axial lengths (r = − 0.548 to − 0.357, all P < 0.001) and greater macular curvatures (r = − 0.542 to − 0.305, all P < 0.001). The CT and ST were significantly thinner in eyes with posterior staphyloma than in those without at all measurement points (all P ≤ 0.006) but did not differ between eyes with the wide macular and narrow macular type of staphyloma. Eyes with myopic maculopathy of category ≥ 3 according to the International Meta-Analysis for Pathologic Myopia classification had significantly thinner CTs and STs than those with category ≤ 2 (all P ≤ 0.005). In highly myopic eyes, a decrease in the CT and ST was more pronounced in eyes with more structural changes, such as longer axial length, steeper macular curvature, and the presence of posterior staphyloma.
An efficient vector-based CRISPR/Cas9 system in an Oreochromis mossambicus cell line using endogenous promoters
Authors: Hamar Jens , Kültz Dietmar 
Published: April 2021

AbstractCRISPR/Cas9 gene editing is effective in manipulating genetic loci in mammalian cell cultures and whole fish but efficient platforms applicable to fish cell lines are currently limited. Our initial attempts to employ this technology in fish cell lines using heterologous promoters or a ribonucleoprotein approach failed to indicate genomic alteration at targeted sites in a tilapia brain cell line (OmB). For potential use in a DNA vector approach, endogenous tilapia beta Actin (OmBAct), EF1 alpha (OmEF1a), and U6 (TU6) promoters were isolated. The strongest candidate promoter determined by EGFP reporter assay, OmEF1a, was used to drive constitutive Cas9 expression in a modified OmB cell line (Cas9-OmB1). Cas9-OmB1 cell transfection with vectors expressing gRNAs driven by the TU6 promoter achieved mutational efficiencies as high as 81% following hygromycin selection. Mutations were not detected using human and zebrafish U6 promoters demonstrating the phylogenetic proximity of U6 promoters as critical when used for gRNA expression. Sequence alteration to TU6 improved mutation rate and cloning efficiency. In conclusion, we report new tools for ectopic expression and a highly efficient, economical system for manipulation of genomic loci and evaluation of their causal relationship with adaptive cellular phenotypes by CRISPR/Cas9 gene editing in fish cells.
Prevalence of lipase producer Aspergillus niger in nuts and anti-biofilm efficacy of its crude lipase against some human pathogenic bacteria
Authors: Yassein Asmaa S. , Hassan Mohamed M. , Elamary Rokaia B. 
Published: April 2021

AbstractNuts are the natural source of healthy lipids, proteins, and omega-3. They are susceptible to fungal and mycotoxins contamination because of their high nutritional value. Twenty-five species comprising 12 genera were isolated from 80 samples of dried fruits and nuts using the dilution plate method. Peanut recorded the highest level of contamination followed by coconut; almond and raisin were the lowest. Aspergillus was the most prevalent genus and A.niger, was the most dominant species. The morphological identification of the selected A.niger isolates as they were detected in high frequency of occurrence was confirmed by using 18SrRNA sequence. Ochratoxin biosynthesis gene Aopks was detected in the tested isolates. Lipase production by the selected A.niger isolates was determined with enzyme activity index (EAI) ranging from 2.02 to 3.28. A.niger-26 was the highest lipase producer with enzyme activity of 0.6 ± 0.1 U/ml by the trimetric method. Lip2 gene was also detected in the tested isolates. Finally, the antibacterial and antibiofilm efficiency of crude lipase against some human pathogens was monitored. Results exhibited great antibacterial efficacy with minimum bactericidal concentration (MBC) of 20 to 40 µl/100 µl against Escherichiacoli, Pseudomonasaeruginosa, Proteusmirabilis, and Methicillin-resistant Staphylococcusaureus (MRSA). Interestingly, significant anti-biofilm efficacy with inhibition percentages of 95.3, 74.9, 77.1 and 93.6% was observed against the tested pathogens, respectively.
Social and ethnic disparities in stillbirth and infant death in Denmark, 2005–2016
Authors: Damsted Rasmussen Trine , Villadsen Sarah Fredsted , Kragh Andersen Per , Smith Jervelund Signe , Nybo Andersen Anne-Marie 
Published: April 2021

AbstractEthnic disparity in stillbirth and infant death has been demonstrated in Europe. As the relation between migration and health change over time, this population based register study investigated the recent figures and explored if potential differences could be explained by the well-known educational and income inequalities in stillbirth and infant death using a novel approach. Stillbirth and infant mortality varied considerably according to country of origin, with only immigrants from China, Norway, and Poland having an overall lower risk than Danish women. Women of Pakistani, Turkish, and Somali origin had a particularly high risk of both outcomes. Women from recent high conflict areas displayed a pattern with increased stillbirth risk. An observed excess risks across generations was found, which is disturbing and rule out factors related to language barriers or newness. Differences in educational level and household income explained only part of the observed inequalities. Strengthening of the maternity care system to better understand and meet the needs of immigrant women seems needed to mitigate the disparities.
Comprehensive surgical treatment strategy for spinal metastases
Authors: Wagner Arthur , Haag Elena , Joerger Ann-Kathrin , Jost Philipp , Combs Stephanie E. , Wostrack Maria , Gempt Jens , Meyer Bernhard 
Published: April 2021

AbstractThe management of patients with spinal metastases (SM) requires a multidisciplinary team of specialists involved in oncological care. Surgical management has evolved significantly over the recent years, which warrants reevaluation of its role in the oncological treatment concept. Any patient with a SM was screened for study inclusion. We report baseline characteristics, surgical procedures, complication rates, functional status and outcome of a large consecutive cohort undergoing surgical treatment according to an algorithm. 667 patients underwent 989 surgeries with a mean age of 65 years (min/max 20–94) between 2007 and 2018. The primary cancers mostly originated from the prostate (21.7%), breast (15.9%) and lung (10.0%). Surgical treatment consisted of dorsoventral stabilization in 69.5%, decompression without instrumentation in 12.5% and kyphoplasty in 18.0%. Overall survival reached 18.4 months (95% CI 9.8–26.9) and the median KPS increased by 10 within hospital stay. Surgical management of SMs should generally represent the first step of a conclusive treatment algorithm. The need to preserve long-term symptom control and biomechanical stability requires a surgical strategy currently not supported by level I evidence.
The quantitative comparison between high wall shear stress and high strain in the formation of paraclinoid aneurysms
Authors: Kim Jung-Jae , Yang Hyeondong , Kim Yong Bae , Oh Je Hoon , Cho Kwang-Chun 
Published: April 2021

AbstractIn the hemodynamic study, computational fluid dynamics (CFD) analysis has shown that high wall shear stress (WSS) is an important parameter in cerebral aneurysm formation. However, CFD analysis is not more realistic than fluid–structure interaction (FSI) analysis given its lack of considering the involvement of vascular structures. To investigate the relationship between the hemodynamic parameters and the aneurysm formation, the locations of high WSS and high strain were extracted from the CFD and FSI analyses, respectively. Then the distances between the aneurysm formation site and the locations of high WSS or high strain were calculated. A total of 37 intracranial paraclinoid aneurysms were enrolled for quantitative comparison. Additionally, the dura mater was modeled to facilitate realistic results in FSI analysis. The average distance from the location of the aneurysm formation site to the high strain (1.74 mm $$\pm $$
±
1.04 mm) was smaller than the average distance to the high WSS (3.33 mm $$\pm $$
±
1.18 mm). The presence of dura mater also influenced the findings in the aneurysm formation site. High strain extracted by FSI analysis is an important hemodynamic factor related to the formation of cerebral aneurysms. Strain parameter could help to predict the formation of aneurysms and elucidate the appropriate treatment.
A combined RAD-Seq and WGS approach reveals the genomic basis of yellow color variation in bumble bee Bombus terrestris
Authors: Rahman Sarthok Rasique , Cnaani Jonathan , Kinch Lisa N. , Grishin Nick V. , Hines Heather M. 
Published: April 2021

AbstractBumble bees exhibit exceptional diversity in their segmental body coloration largely as a result of mimicry. In this study we sought to discover genes involved in this variation through studying a lab-generated mutant in bumble bee Bombus terrestris, in which the typical black coloration of the pleuron, scutellum, and first metasomal tergite is replaced by yellow, a color variant also found in sister lineages to B. terrestris. Utilizing a combination of RAD-Seq and whole-genome re-sequencing, we localized the color-generating variant to a single SNP in the protein-coding sequence of transcription factor cut. This mutation generates an amino acid change that modifies the conformation of a coiled-coil structure outside DNA-binding domains. We found that all sequenced Hymenoptera, including sister lineages, possess the non-mutant allele, indicating different mechanisms are involved in the same color transition in nature. Cut is important for multiple facets of development, yet this mutation generated no noticeable external phenotypic effects outside of setal characteristics. Reproductive capacity was reduced, however, as queens were less likely to mate and produce female offspring, exhibiting behavior similar to that of workers. Our research implicates a novel developmental player in pigmentation, and potentially caste, thus contributing to a better understanding of the evolution of diversity in both of these processes.
Blood pressure dipping during REM and non-REM sleep in patients with moderate to severe obstructive sleep apnea
Authors: BaHammam Ahmed S. , Alshahrani Mana , Aleissi Salih A. , Olaish Awad H. , Alhassoon Mohammed H. , Shukr Afnan 
Published: April 2021

AbstractA limited number of papers have addressed the association between non-dipping-blood pressure (BP) obstructive sleep apnea (OSA), and no study has assessed BP-dipping during rapid eye movement (REM) and non-REM sleep in OSA patients. This study sought to noninvasively assess BP-dipping during REM and non-REM (NREM)-sleep using a beat-by-beat measurement method (pulse-transit-time (PTT)). Thirty consecutive OSA patients (men = 50%) who had not been treated for OSA before and who had > 20-min of REM-sleep were included. During sleep, BP was indirectly determined via PTT. Patients were divided into dippers and non-dippers based on the average systolic-BP during REM and NREM-sleep. The studied group had a a median age of 50 (42–58.5) years and a body mass index of 33.8 (27.6–37.5) kg/m2. The median AHI of the study group was 32.6 (20.1–58.1) events/h (range: 7–124), and 89% of them had moderate-to-severe OSA. The prevalence of non-dippers during REM-sleep was 93.3%, and during NREM-sleep was 80%. During NREM sleep, non-dippers had a higher waist circumference and waist-hip-ratio, higher severity of OSA, longer-time spent with oxygen saturation < 90%, and a higher mean duration of apnea during REM and NREM-sleep. Severe OSA (AHI ≥ 30) was defined as an independent predictor of non-dipping BP during NREM sleep (OR = 19.5, CI: [1.299–292.75], p-value = 0.03). This short report demonstrated that BP-dipping occurs during REM and NREM-sleep in patients with moderate-to-severe OSA. There was a trend of more severe OSA among the non-dippers during NREM-sleep, and severe OSA was independently correlated with BP non-dipping during NREM sleep.
Detecting early onset of anthracyclines-induced cardiotoxicity using a novel panel of biomarkers in West-Virginian population with breast cancer
Authors: Lakhani Hari Vishal , Pillai Sneha S. , Zehra Mishghan , Dao Benjamin , Tirona Maria Tria , Thompson Ellen , Sodhi Komal 
Published: April 2021

AbstractCardiotoxic manifestation associated with breast cancer treatment by anthracycline regimen increases patients’ susceptibility to myocardial injury, reduction in left ventricular ejection fraction and complications associated with heart failure. There is currently no standardized, minimally invasive, cost effective and clinically verified procedure to monitor cardiotoxicity post-anthracycline therapy initiation, and to detect early onset of irreversible cardiovascular complications. This study aims to create a panel of novel biomarkers and circulating miRNAs associated with cardiotoxicity, further assessing their correlation with cardiac injury specific markers, troponin I and T, and demonstrate the development of cardiac dysfunction in breast cancer patients. Blood obtained from West Virginian females clinically diagnosed with breast cancer and receiving anthracyclines showed upregulated level of biomarkers and circulating miRNAs after 3 and 6 months of chemotherapy initiation with increased levels of cardiac troponin I and T. These biomarkers and miRNAs significantly correlated with elevated troponins. Following 6 months of anthracycline-regimens, 23% of the patient population showed cardiotoxicity with reduced left ventricular ejection fraction. Our results support the clinical application of plasma biomarkers and circulating miRNAs to develop a panel for early diagnosis of chemotherapy related cardiac dysfunction which will enable early detection of disease progression and management of irreversible cardiac damage.
Girls exhibit greater empathy than boys following a minor accident
Authors: Benenson Joyce F. , Gauthier Evelyne , Markovits Henry 
Published: April 2021

AbstractHundreds of studies find that girls and women report feeling greater empathy than boys and men in response to adverse events befalling others. Despite this, few non-self-report measures demonstrate similar sex differences. This produces the oft-cited conclusion that to conform to societal expectations of appropriate sex-typed behavior females report higher levels of empathy. Several studies of sex differences in areas of brain activation and on infants’ and young children’s behavior however provide suggestive findings that self-reports reflect actual underlying sex differences in experiencing concern about others. We demonstrate using behavioral indices that females experience more empathy than males after witnessing an adverse event befall a same-sex classmate. In our study, one member of a pair experienced a minor accident on the way to constructing a tower while a bystander observed. We measured whether bystanders ceased their ongoing activity, looked at the victim, waited for the victim to recover from the accident, and actively intervened to help the victim. Female more than male bystanders engaged in these activities. These behavioral results suggest that an adverse event produces different subjective experiences in females than males that motivate objectively different behaviors, consistent with findings from self-report measures of empathy.