Miracle-dz/UniFAR-FTUs huggingface dataset:
Compound computer vision workflow for efficient and automated immunohistochemical analysis of whole slide images

Aims Immunohistochemistry (IHC) assessment of tissue is a central component of the modern pathology workflow, but quantification is challenged by subjective estimates by pathologists or manual steps in semi-automated digital tools. This study integrates various computer vision tools to develop a fully automated workflow for quantifying Ki-67, a standard IHC test used to assess cell proliferation on digital whole slide images (WSIs). Methods We create an automated nuclear segmentation strategy by deploying a Mask R-CNN classifier to recognise and count 3,3′-diaminobenzidine positive and negative nuclei. To further improve automation, we replaced manual selection of regions of interest (ROIs) by aligning Ki-67 WSIs with corresponding H&E-stained sections, using scale-invariant feature transform (SIFT) and a conventional histomorphological convolutional neural networks to define tumour-rich areas for quantification. Results The Mask R-CNN was tested on 147 images generated from 34 brain tumour Ki-67 WSIs and showed a high concordance with aggregate pathologists’ estimates ( n = 3 assessors; y = 0.9712 x − 1.945 , r=0.9750). Concordance of each assessor’s Ki-67 estimates was higher when compared with the Mask R-CNN than between individual assessors (ravg=0.9322 vs 0.8703; p=0.0213). Coupling the Mask R-CNN with SIFT-CNN workflow demonstrated ROIs can be automatically chosen and partially sampled to improve automation and dramatically decrease computational time (average: 88.55–19.28 min; p<0.0001). Conclusions We show how innovations in computer vision can be serially compounded to automate and improve implementation in clinical workflows. Generalisation of this approach to other ancillary studies has significant implications for computational pathology.
Fine-grained calibrated double-attention convolutional network for left ventricular segmentation

Objective. Left ventricular (LV) segmentation of cardiac magnetic resonance imaging (MRI) is essential for diagnosing and treating the early stage of heart diseases. In convolutional neural networks, the target information of the LV in feature maps may be lost with convolution and max-pooling, particularly at the end of systolic. Fine segmentation of ventricular contour is still a challenge, and it may cause problems with inaccurate calculation of clinical parameters (e.g. ventricular volume). In order to improve the similarity of the neural network output and the target segmentation region, in this paper, a fine-grained calibrated double-attention convolutional network (FCDA-Net) is proposed to finely segment the endocardium and epicardium from ventricular MRI. Approach. FCDA-Net takes the U-net as the backbone network, and the encoder-decoder structure incorporates a double grouped-attention module that is constructed by a fine calibration spatial attention module (fcSAM) and a fine calibration channel attention module (fcCAM). The double grouped-attention mechanism enhances the expression of information in both spatial and channelwise feature maps to achieve fine calibration. Main Results. The proposed approach is evaluated on the public MICCAI 2009 challenge dataset, and ablation experiments are conducted to demonstrate the effect of each grouped-attention module. Compared with other advanced segmentation methods, FCDA-Net can obtain better LV segmentation performance. Significance. The LV segmentation results of MRI can be used to perform more accurate quantitative analysis of many essential clinical parameters and it can play an important role in image-guided clinical surgery.
In silico discovery of novel inhibitors from Northern African natural products database against main protease (Mpro) of SARS-CoV-2

Abstract The recent outbreak of COVID-19 (Coronavirus Disease 2019), caused by a novel SARS-CoV-2 virus, has led to public health emergencies worldwide where time is as important as equipment to save lives. Antimalarial drugs such as hydroxychloroquine and chloroquine derivatives are used in emergencies but they are not suitable for patients with high blood pressure, diabetes and heart problems. Since there are no approved drugs for this disease, science is challenged to find vaccines and new drugs. Therefore, as part of our Silico drug design strategy, we identified drug-like compounds that inhibit replication of the main protease (Mpro) of SARS-CoV-2 based on receptor-based virtual database screening, molecular docking, molecular dynamics, and drug-similarity profiling from the NANPDB natural products database available at North African. The two resulting hit compounds named 5- Chloro-Omega-hydroxy-1-O-methylemodin and cystodion E showed the highest binding energy with Mpro of SARS-CoV-2 and strong inhibitory activity compared with the previously published N3 inhibitor. The complexes of these two compounds were validated by molecular dynamics analysis (RMSD, RMSF, Rg, total number of hydrogen bonds and secondary structure fractions of the protein in the complex) as the best method to evaluate the biological stability of the system. Therefore, these molecules deserve more attention in drug development compared to COVID-19. Highlights A large database of natural compounds was screened against nCoV-2's Mpro. Molecular docking and Molecular dynamics were used as powerful methods. Two compounds were found are very attractive to inhibit Mpro of nCoV-2. ADME-Tox profiling is evaluated the active compounds are not cancerogenic. Communicated by Ramaswamy H. Sarma
Coronary Artery Bypass Grafting and Percutaneous Coronary Intervention in Patients With Chronic Total Occlusion and Multivessel Disease

Supplemental Digital Content is available in the text. Background: Percutaneous coronary intervention (PCI) has been used increasingly as an alternative means of revascularization for patients with chronic total occlusion and multivessel disease. We investigated 5-year clinical outcomes following coronary artery bypass grafting (CABG) and PCI in patients with chronic total occlusion and multivessel disease. Methods: In this single-center, retrospective cohort study, 4324 consecutive patients with ≥1 chronic total occlusion and multivessel disease were treated with either CABG (n=2264) or PCI (n=2060) between 2010 and 2013. The primary outcome was 5-year composite of death, myocardial infarction, or stroke. An inverse-probability-of-treatment weighting method was used adjusting for both patient and lesion characteristics. Results: The unadjusted 5-year composite outcomes were similar between CABG group and PCI group (12.1% [258/2264] versus 11.4% [218/2060]; P=0.52). After adjustment for baseline variables, PCI was associated with significantly higher risk of composite outcomes (adjusted hazard ratio: 1.21 [95% CI, 1.02–1.44]; P=0.03). The inferiority of PCI in 5-year composite outcome was significant in patients with CABG recommendation according to SYNTAX (Synergy Between Percutaneous Coronary Intervention With Taxus and Cardiac Surgery) score II (adjusted hazard ratio: 1.55 [95% CI, 1.14–2.09]; P=0.005) but not evident in patients with PCI or PCI/CABG equipoise recommendation according to SYNTAX score II (adjusted hazard ratio: 0.94 [95% CI, 0.75–1.17]; P=0.56). A similar risk of 5-year composite outcomes was observed between CABG and PCI with residual SYNTAX score ≤8. Conclusions: In this single-center retrospective study among patients with chronic total occlusion and multivessel disease, PCI was associated with higher risk of 5-year composite death, myocardial infarction, or stroke.
Dysregulated circulating miR-4429 serves as a novel non-invasive biomarker and is correlated with EGFR mutation in patients with non-small cell lung cancer

This study aimed to investigate the correlation between microRNA (miR)-4429 and epidermal growth factor receptor (EGFR), the expression, and clinical significance of miR-4429 in patients with non-small cell lung cancer (NSCLC), and the relationship between miR-4429 and EGFR mutation in NSCLC patients. Blood samples were collected from 122 NSCLC patients and 72 healthy volunteers. miR-4429 expression and EGFR mRNA expression were detected by real-time quantitative polymerase chain reaction. Correlation between miR-4429 and EGFR was evaluated by dual-luciferase reporter assay and the Pearson correlation analysis. The ability of serum miR4429 to discriminate between NSCLC patients and healthy controls, and to discriminate between EGFR wild-type (EGFR-W) and EGFR mutant-type (EGFR-M) patients was assessed using receiver operating characteristic analysis. The relationship between miR-4429 and NSCLC patients’ survival was identified by KaplanMeier survival curves and log-rank test. The prognostic value of miR-4429 in NSCLC patients was evaluated by Cox regression analysis. miR-4429 could directly bind to EGFR. Serum miR-4429, decreased in NSCLC patients, was negatively correlated with serum EGFR mRNA expression in NSCLC patients. In addition, miR-4429 had a high diagnostic value for screening NSCLC patients from healthy controls, and was independently correlated with survival prognosis of NSCLC patients. Moreover, miR4429 was decreased in EGFR-M patients, which had a certain screening ability for EGFRM patients. Our findings indicate that miR-4429 is negatively correlated with EGFR in NSCLC, and may function as a diagnostic and prognostic biomarker for NSCLC patients. Additionally, miR-4429 is associated with EGFR mutation in NSCLC patients.
Radiographic Comparison of Heterotopic Ossification After Primary Total Ankle Arthroplasty in Fourth-Generation Implants

Heterotopic ossification (HO) is a known sequela in total ankle arthroplasty. The purpose of this study was to determine the radiographic incidence of HO in fourth-generation total ankle implants including the INFINITY, CADENCE, and VANTAGE. Radiographs were assessed for the incidence and location of HO in each implant using the modified Brooker classification. Seventy-one patients were included. There were 41 INFINITY, 16 CADENCE, and 14 VANTAGE implants. The average radiographic follow-up was 19.7 months. The incidence of HO was 69.0%. Overall, the HO was Class I in 31 cases (63.3%); Class II in 7 cases (14.3%); Class III in 10 cases (20.4%); and Class IV in 1 case (2.0%). For INFINITY; n = 33 patients (80.5%), CADENCE; n = 8 patients (50%); VANTAGE n = 8 patients (57.1%). When comparing INFINITY with CADENCE/VANTAGE, there was a statistically significant difference in presence of HO (P = 0.01). When comparing INFINITY with CADENCE, there was a statistically significant difference in presence of HO (P = 0.04). In the 33 cases of INFINITY with HO, 30 had neutral or posterior coverage, and in 4 cases, the prosthesis did not extend to the posterior tibial cortex (P = 0.005). This study demonstrates a continued high rate of HO with 3 fourth-generation ankle implants in the short term, although many were Class 1 and posterior. The INFINITY had a higher overall incidence of HO. Adequate posterior cortical coverage did not play a role in radiographic presence of HO. Further research is warranted with longer-term follow-up to determine the clinical and radiographic significance of HO. Level of Evidence: Level III: Retrospective comparative
Bleb Analysis Using Anterior Segment Optical Coherence Tomography and Surgical Predictors of XEN Gel Stent

Purpose To determine the early predictors of surgical success 6 months after XEN surgery among clinical parameters, including anterior segment optical coherence tomography (AS-OCT). Methods A total of 31 eyes with medically uncontrolled primary open-angle glaucoma or pseudoexfoliation glaucoma was enrolled retrospectively. Using AS-OCT, XEN tip location was categorized into intraconjunctival, intratenon, or uviform at day 1 and blebs were classified into no or low, high sparse, high thick, cystic, or mixed walls at month 6. Using slit-lamp photography, blebs were classified into no or low, localized avascular, diffuse avascular, localized vascular, or diffuse vascular blebs at month 6. Surgical success was defined as an intraocular pressure (IOP) of less than 14 mm Hg. Results Intraconjunctival and intratenon locations of the tip mostly created a high sparse wall, whereas the uviform type mostly created no or low wall and no or low bleb. The uviform type was linked to pseudoexfoliation glaucoma. A high sparse wall and diffuse avascular bleb showed a lower mean IOP than a high thick wall and localized vascular bleb. In the multivariate analysis, female sex and IOP at week 1 were early predictors of surgical success (8.45 times and 33.1% per 1 mm Hg-decrease, respectively). Conclusions Bleb evaluation using AS-OCT is valuable to correlate tip location and bleb morphology with clinical profiles, considering that a lower early postoperative IOP is linked to surgical success. Translational Relevance Bleb analysis using AS-OCT on day 1 could help to predict bleb morphology after 6 months, which is important to maintain the functioning bleb in the longer term.
Human antibodies against noncircumsporozoite proteins block Plasmodium falciparum parasite development in hepatocytes

Sporozoite-based approaches currently represent the most effective vaccine strategies for induction of sterile protection against Plasmodium falciparum (Pf) malaria. Clinical development of subunit vaccines is almost exclusively centered on the circum-sporozoite protein (CSP), an abundantly expressed protein on the sporozoite membrane. Anti-CSP antibodies are able to block sporozoite invasion and development in human hepatocytes and subsequently prevent clinical malaria. Here, we have investigated whether sporozoite-induced human antibodies with specificities different from CSP can reduce Pf-liver stage development. IgG preparations were obtained from 12 volunteers inoculated with a protective immunization regime of whole sporozoites under chloroquine prophylaxis. These IgGs were depleted for CSP specificity by affinity chromatography. Recovered non-CSP antibodies were tested for sporozoite membrane binding and for functional inhibition of sporozoite invasion of a human hepatoma cell line and hepatocytes both in vitro and in vivo. Postimmunization IgGs depleted for CS specificity of 9 of 12 donors recognized sporozoite surface antigens. Samples from 5 of 12 donors functionally reduced parasite-liver cell invasion or development using the hepatoma cell line HC-04 and FRG-huHep mice containing human liver cells. The combined data provide clear evidence that non-CSP proteins, as yet undefined, do represent antibody targets for functional immunity against Pf parasites responsible for malaria.
Group B Streptococcal Neonatal Meningitis

Neonatal bacterial meningitis is a devastating disease, associated with high mortality and neurological disability, in both developed and developing countries. Streptococcus agalactiae, commonly referred to as group B Streptococcus (GBS), remains the most common bacterial cause of meningitis among infants younger than 90 days. Maternal colonization with GBS in the gastrointestinal and/or genitourinary tract is the primary risk factor for neonatal invasive disease. SUMMARY Neonatal bacterial meningitis is a devastating disease, associated with high mortality and neurological disability, in both developed and developing countries. Streptococcus agalactiae, commonly referred to as group B Streptococcus (GBS), remains the most common bacterial cause of meningitis among infants younger than 90 days. Maternal colonization with GBS in the gastrointestinal and/or genitourinary tracts is the primary risk factor for neonatal invasive disease. Despite prophylactic intrapartum antibiotic administration to colonized women and improved neonatal intensive care, the incidence and morbidity associated with GBS meningitis have not declined since the 1970s. Among meningitis survivors, a significant number suffer from complex neurological or neuropsychiatric sequelae, implying that the pathophysiology and pathogenic mechanisms leading to brain injury and devastating outcomes are not yet fully understood. It is imperative to develop new therapeutic and neuroprotective approaches aiming at protecting the developing brain. In this review, we provide updated clinical information regarding the understanding of neonatal GBS meningitis, including epidemiology, diagnosis, management, and human evidence of the disease's underlying mechanisms. Finally, we explore the experimental models used to study GBS meningitis and discuss their clinical and physiologic relevance to the complexities of human disease.
Habitatwahl des Uhus (Bubo bubo) im Südwesten Niederösterreichs und in den donaunahen Gebieten des Mühlviertels auf Basis radiotelemetrischer Untersuchungen

L e d it z n i g Ch., 1996: Die Auswertung des Lebensraum-Nutzung durch den Uhu erfolgte mittels eines speziell entwickelten „Wildokologischen Bestands­ typs“ auf der Basis radiotelemetrisch ermittelter Daten. Wesentlich fur das Home Range, das im Untersuchungsgebiet eine Grose von bis zu 138 km2 (keine geschlechtsspezifischen Unterschiede) aufweist, sind offene Flachen und Gewasser, die sowohl ein ausreichendes Arten- als auch Individuenspektrum an Beutetieren bieten. Je hoher im Home Range der Waldanteil wird, der unter den derzeitigen, im Untersuchungsgebiet vorherrschenden forstwirtschaftlichen Bedingungen fast ausschlieslich als Tageseinstand vom Uhu Verwendung findet, desto starker sinkt die Reproduktionsrate des Einzelpaares, und zwar vor allem deshalb, weil der Flachenanteil mit verfugbarer Beute sinkt. Der Brut­ erfolg wird besonders stark auch durch das Verhaltnis der Flugdistanz vom Brutplatz zum Jagdgebiet der Groseule und dem mittleren Beutetiergewicht bestimmt. Sinkt dieses Verhaltnis, das als Energiebilanzindex bezeichnet wird, auf 0,1 oder darunter, kann mit keiner erfolgreichen Brut mehr gerechnet werden. L e d it z n i g Ch., 1996: Habitat selection in the Eagle Owl (Bubo bubo) in southwestem Lower Austria and areas proximate to the Danube river in Muhlviertel using radio-telemetry. The home range analysis of the Eagle Owl (Bubo bubo) was carried out based on a radio-telemetry data collection method called "wildlife ecological popula­ tion type", which was developed specifically for this species. Important factors for home range which averaged 138 km2 and showed no size difference be­ tween <? <f and ? are open areas and waters which offer a sufficient spectrum of species and individual prey. The more wooded area in the home range, the lower is the reproductive success of single pairs primarily because of reduced prey abundance. To a large extent, these wooded areas are currently under the influence of forestry practices and are used by the owls almost exclusively during the day. The brood success is also influenced by the relation between flight distance from the breeding area to hunting area and the average prey weight. If this relation-, which is calculated as an energy index, falls to 0.1 or below, fledging success is unlikely.
Targeting IRE1 endoribonuclease activity alleviates cardiovascular lesions in a murine model of Kawasaki disease vasculitis

Kawasaki disease (KD) is the leading cause of noncongenital heart disease in children. Studies in mice and humans propound the NLRP3/IL-1β pathway as the principal driver of KD pathophysiology. Endoplasmic reticulum (ER) stress can activate the NLRP3 inflammasome, but the potential implication of ER stress in KD pathophysiology has not been investigated to our knowledge. We used human patient data and the Lactobacillus casei cell wall extract (LCWE) murine model of KD vasculitis to characterize the impact of ER stress on the development of cardiovascular lesions. KD patient transcriptomics and single-cell RNA sequencing of the abdominal aorta from LCWE-injected mice revealed changes in the expression of ER stress genes. Alleviating ER stress genetically, by conditional deletion of inositol-requiring enzyme 1 (IRE1) in myeloid cells, or pharmacologically, by inhibition of IRE1 endoribonuclease (RNase) activity, led to significant reduction of LCWE-induced cardiovascular lesion formation as well as reduced caspase-1 activity and IL-1β secretion. These results demonstrate the causal relationship of ER stress to KD pathogenesis and highlight IRE1 RNase activity as a potential new therapeutic target.
The Susceptibility of LNA(Low Noise Amplifier) Due To Front-Door Coupling Under Narrow-Band High Power Electromagnetic Wave

This study has examined susceptibility of LNA(Low Noise Amplifier) due to Front-Door Coupling under Narrow-Band high power electromagnetic wave. M/DFR(Malfunction/Destruction Failure Rate) was measured to investigate the diagnostic of IC test. In addition, decapsulation analysis was used to understand the inside of the chip state in LNA devices. The experiments is employed as an open-ended waveguide to study the destruction effects of LNA using a 2.45 GHz Magnetron as a high power electromagnetic wave. The susceptibility level of LNA was assessed by electric field strength, and its failure modes were observed. The malfunction of LNA device has showed as the type of self-reset and power-reset. The electric field strength of malfunction threshold is 524 V/m and 1150 V/m respectively. Also, he electric field of destruction threshold is 1530 V/m. Three types of damaged LNA were observed by decapsulation analysis: component, onchipwire, and bondwire destruction. Based on these results, the susceptibility of the LNA can be applied to a database to help elucidate the effects of microwaves on electronic equipment. 요 약 본 연구는 안테나에 커플링되는 협대역 고출력 전자기파에 대한 저 잡음 증폭기(LNA)의 민감성 특성을 알아보 았다. LNA 소자의 오동작/파괴는 MFR/DFR((Malfunction Failure Rate/Destruction Failure Rate)을 이용하여 소 자의 민감성을 확인하였다. 그리고 LNA 소자의 내부 칩 상태는 Decapsulation 분석을 이용하여 손상부위를 관찰 하였다. 협대역 고출력 전자기파 장치는 2.45 GHz 마그네트론을 사용하였고, LNA의 민간성 레벨은 협대역 고출 력 전자기파의 전계강도에 따라 오동작/파괴율을 평가하였다. 그 결과, LNA 소자의 오동작은 셀프리셋(Self Reset)과 파워리셋(Power Reset)의 형태로 나타내었고, 이때 오동작 임계 전계강도는 각각 524 V/m, 1150 V/m로 측정되었다. 그리고 LNA의 소자의 파괴 임계 전계강도는 1530 V/m이다. 협대역 고출력 전자기파에 의한 LNA 소자의 내부 칩 파괴는 본드와이어, 온칩와이어 그리고 컴포넌트 세가지 형태로 관찰되었다. 이 결과로, 협대역 고 출력 전자기파에 의한 반도체 전자회로의 내성평가 자료로 활용할 수 있을 것으로 판단된다.