Miracle-dz/UniFAR-FTUs huggingface dataset:
Bedside 3D Visualization of Lymphatic Vessels with a Handheld Multispectral Optoacoustic Tomography Device

Identification of lymphatics by Indocyanine Green (ICG) lymphography in patients with severe lymphedema is limited due to the overlying dermal backflow. Nor can the method detect deep and/or small vessels. Multispectral optoacoustic tomography (MSOT), a real-time three- dimensional (3D) imaging modality which allows exact spatial identification of absorbers in tissue such as blood and injected dyes can overcome these hurdles. However, MSOT with a handheld probe has not been performed yet in lymphedema patients. We conducted a pilot study in 11 patients with primary and secondary lymphedema to test whether lymphatic vessels could be detected with a handheld MSOT device. In eight patients, we could not only identify lymphatics and veins but also visualize their position and contractility. Furthermore, deep lymphatic vessels not traceable by ICG lymphography and lymphatics covered by severe dermal backflow, could be clearly identified by MSOT. In three patients, two of which had advanced stage lymphedema, only veins but no lymphatic vessels could be identified. We found that MSOT can identify and image lymphatics and veins in real-time and beyond the limits of near-infrared technology during a single bedside examination. Given its easy use and high accuracy, the handheld MSOT device is a promising tool in lymphatic surgery.
Finite-Horizon H∞ Bipartite Consensus Control of Cooperation–Competition Multiagent Systems With Round-Robin Protocols

This article focuses on the finite-horizon <inline-formula> <tex-math notation="LaTeX">$\mathcal {H}_{\infty }$ </tex-math></inline-formula> bipartite consensus control problem for a class of discrete time-varying cooperation–competition multiagent systems (DTV-CCMASs) with the round-robin (RR) protocol. The cooperation–competition relationship among agents is characterized by a signed graph, whose edges are with positive or negative connection weights. Specifically, a positive weight corresponds to an allied relationship between two agents and a negative one means an adversary relationship. The data exchange between each agent and its neighbors is orchestrated by an RR protocol, where only one neighboring agent is authorized to transmit the data packet at each time instant, and therefore, the data collision is prevented. This article aims to design a bipartite consensus controller for DTV-CCMASs with the RR protocol such that the predetermined <inline-formula> <tex-math notation="LaTeX">$\mathcal {H}_{\infty }$ </tex-math></inline-formula> bipartite consensus is satisfied over a given finite horizon. A sufficient condition is first established to guarantee the desired <inline-formula> <tex-math notation="LaTeX">$\mathcal {H}_{\infty }$ </tex-math></inline-formula> bipartite consensus by resorting to the completing square method. With the help of an auxiliary cost combined with the Moore–Penrose pseudoinverse method, a design scheme of the bipartite consensus controller is obtained by solving two coupled backward recursive Riccati difference equations (BRRDEs). Finally, a simulation example is given to verify the effectiveness of the proposed scheme of the bipartite consensus controller.
Optimizing COPD treatment in patients with lung- or head and neck cancer does not improve quality of life – a randomized, pilot, clinical trial

ABSTRACT Background: Chronic obstructive pulmonary disease (COPD) is a common comorbidity in patients with lung and head- and neck cancer. Patients with lung cancer who also suffer from COPD have a worse prognosis than patients with lung cancer and no COPD. It has previously been shown that diagnosis and treatment of concomitant COPD in patients with newly diagnosed lung- or head and neck cancer need optimization. In this randomized, controlled trial we aimed to assess if intervention directed at improving treatment for COPD in these patients improved health-related quality of life (QoL). Methods: During 2014, we randomized 114 patients referred for oncological treatment at a large university hospital in the Capital Region of Denmark, to either usual care or intervention regarding concomitant COPD. The intervention consisted of two visits in an out-patient clinic established at the oncological department and staffed with a pulmonary physician. At baseline, week 13 and week 25, all patients filled out the cancer- and COPD-specific QoL questionnaires CAT and EORTC, respectively. The primary outcome was change in CAT-score between control- and intervention group. The secondary outcome was change in EORTC. Results: There was no change in CAT-score by week 13 or 25 between the groups. For the EORTC there was a statistically significant improvement only in the fatigue domain at week 13 (p = 0.03), but not at week 25. There was a trend towards less dyspnea in the intervention group at week 13, measured by EORTC (p = 0.07). Mortality by week 25 was similar in both groups. Conclusion: In this population of severely ill cancer patients, we did not find that this intervention, focusing on inhaled COPD medication, for the management of COPD had any convincing positive impact on the patients’ perceived quality of life compared with usual care. Further studies are needed.
Collagen Turnover in Relation to Risk Factors and Hemodynamics in Human Intracranial Aneurysms

Supplemental Digital Content is available in the text. Background and Purpose— Determinants for molecular and structural instability, that is, impending growth or rupture, of intracranial aneurysms (IAs) remain uncertain. To elucidate this, we endeavored to estimate the actual turnover rates of the main molecular constituent in human IA (collagen) on the basis of radiocarbon (14C) birth dating in relation to IA hemodynamics. Methods— Collagen turnover rates in excised human IA samples were calculated using mathematical modeling of 14C birth dating data of collagen in relation to risk factors and histological markers for collagen maturity/turnover in selected IA. Hemodynamics were simulated using image-based computational fluid dynamics. Correlation, logistic regression, and receiver operating characteristic analyses were performed. Results— Collagen turnover rates were estimated in 46 IA (43 patients); computational fluid dynamics could be performed in 20 IA (20 patients). The mean collagen turnover rate (γ) constituted 126% (±1% error) per year. For patients with arterial hypertension, γ was greater than 2600% annually, whereas γ was distinctly lower with 32% (±1% error) per year for patients without risk factors, such as smoking and hypertension. There was a distinct association between histological presence of rather immature collagen in human IA and the presence of modifiable risk factors. Spatial-temporal averaged wall shear stress predicted rapid collagen turnover (odds ratio, 1.6 [95% CI, 1.0–2.7]). Receiver operating characteristic analysis demonstrated a good test accuracy (area under the curve, 0.798 [95% CI, 0.598–0.998]) for average wall shear stress with a threshold ≥4.9 Pa for rapid collagen turnover. Conclusions— Our data indicate that turnover rates and stability of collagen in human IA are strongly associated with the presence of modifiable risk factors and aneurysmal hemodynamics. These findings underline the importance of strict risk factor modification in patients with unruptured IA. Future should include more detailed risk factor data to establish a more causal understanding of hemodynamics and the rupture risk of individual IA.
Abscisic Acid and Jasmonate Metabolisms Are Jointly Regulated During Senescence in Roots and Leaves of Populus trichocarpa

Plant senescence is a highly regulated process that allows nutrients to be mobilized from dying tissues to other organs. Despite that senescence has been extensively studied in leaves, the senescence of ephemeral organs located underground is still poorly understood, especially in the context of phytohormone engagement. The present study focused on filling this knowledge gap by examining the roles of abscisic acid (ABA) and jasmonate in the regulation of senescence of fine, absorptive roots and leaves of Populus trichocarpa. Immunohistochemical (IHC), chromatographic, and molecular methods were utilized to achieve this objective. A transcriptomic analysis identified significant changes in gene expression that were associated with the metabolism and signal transduction of phytohormones, especially ABA and jasmonate. The increased level of these phytohormones during senescence was detected in both organs and was confirmed by IHC. Based on the obtained data, we suggest that phytohormonal regulation of senescence in roots and leaves is organ-specific. We have shown that the regulation of ABA and JA metabolism is tightly regulated during senescence processes in both leaves and roots. The results were discussed with respect to the role of ABA in cold tolerance and the role of JA in resistance to pathogens.
Identification of a master transcription factor and a regulatory mechanism for desiccation tolerance in the anhydrobiotic cell line Pv11

Water is essential for living organisms. Terrestrial organisms are incessantly exposed to the stress of losing water, desiccation stress. Avoiding the mortality caused by desiccation stress, many organisms acquired molecular mechanisms to tolerate desiccation. Larvae of the African midge, Polypedilum vanderplanki, and its embryonic cell line Pv11 tolerate desiccation stress by entering an ametabolic state, anhydrobiosis, and return to active life after rehydration. The genes related to desiccation tolerance have been comprehensively analyzed, but transcriptional regulatory mechanisms to induce these genes after desiccation or rehydration remain unclear. Here, we comprehensively analyzed the gene regulatory network in Pv11 cells and compared it with that of Drosophila melanogaster, a desiccation sensitive species. We demonstrated that nuclear transcription factor Y subunit gamma-like, which is important for drought stress tolerance in plants, and its transcriptional regulation of downstream positive feedback loops have a pivotal role in regulating various anhydrobiosis-related genes. This study provides an initial insight into the systemic mechanism of desiccation tolerance.
Deep Saliency Hashing for Fine-Grained Retrieval

In recent years, hashing methods have been proved to be effective and efficient for large-scale Web media search. However, the existing general hashing methods have limited discriminative power for describing fine-grained objects that share similar overall appearance but have a subtle difference. To solve this problem, we for the first time introduce the attention mechanism to the learning of fine-grained hashing codes. Specifically, we propose a novel deep hashing model, named deep saliency hashing (DSaH), which automatically mines salient regions and learns semantic-preserving hashing codes simultaneously. DSaH is a two-step end-to-end model consisting of an attention network and a hashing network. Our loss function contains three basic components, including the semantic loss, the saliency loss, and the quantization loss. As the core of DSaH, the saliency loss guides the attention network to mine discriminative regions from pairs of images. We conduct extensive experiments on both fine-grained and general retrieval datasets for performance evaluation. Experimental results on fine-grained datasets, including Oxford Flowers, Stanford Dogs, and CUB Birds demonstrate that our DSaH performs the best for the fine-grained retrieval task and beats the strongest competitor (DTQ) by approximately 10% on both Stanford Dogs and CUB Birds. DSaH is also comparable to several state-of-the-art hashing methods on CIFAR-10 and NUS-WIDE.
Perceived Dark Rim Artifact in First-Pass Myocardial Perfusion Magnetic Resonance Imaging Due to Visual Illusion

Objective To demonstrate that human visual illusion can contribute to sub-endocardial dark rim artifact in contrast-enhanced myocardial perfusion magnetic resonance images. Materials and Methods Numerical phantoms were generated to simulate the first-passage of contrast agent in the heart, and rendered in conventional gray scale as well as in color scale with reduced luminance variation. Cardiac perfusion images were acquired from two healthy volunteers, and were displayed by the same gray and color scales used in the numerical study. Before and after k-space windowing, the left ventricle (LV)-myocardium boarders were analyzed visually and quantitatively through intensity profiles perpendicular the boarders. Results k-space windowing yielded monotonically decreasing signal intensity near the LV-myocardium boarder in the phantom images, as confirmed by negative finite difference values near the board ranging −1.07 to −0.14. However, the dark band still appears, which is perceived by visual illusion. Dark rim is perceived in the in-vivo images after k-space windowing that removed the quantitative signal dip, suggesting that the perceived dark rim is a visual illusion. The perceived dark rim is stronger at peak LV enhancement than the peak myocardial enhancement, due to the larger intensity difference between LV and myocardium. In both numerical phantom and in-vivo images, the illusory dark band is not visible in the color map due to reduced luminance variation. Conclusion Visual illusion is another potential cause of dark rim artifact in contrast-enhanced myocardial perfusion MRI as demonstrated by illusory rim perceived in the absence of quantitative intensity undershoot.
Insights into Praziquantel metabolism and potential enantiomeric CYP-mediated drug-drug interaction

The active enantiomer R-Praziquantel (PZQ) shows clinically a lower relative exposure when administered enantiomerically pure compared to a racemic form. We investigated the hypothesis that enantiomer-enantiomer interactions on CYP enzymes could explain this observation and aimed to further deepen the understanding of PZQ metabolism. Firstly, in an in vitro metabolite profiling study, the formation of multiple metabolites per CYP, together with an observed interconversion of cis-4'-OH-PZQ to trans-4'-OH-PZQ in human hepatocytes, pointed out the inadequacy of measuring metabolite formation in kinetic studies. Thus, a substrate depletion approach to study PZQ enantiomeric interactions was applied. Secondly, an abundant CYP 3A4 metabolite found in previous studies was structurally characterized. Thirdly, substrate depletion methodologies were applied to determine CYP enzyme kinetics of PZQ and to further estimate enantiomer-enantiomer inhibitory parameters. A competitive inhibition between PZQ enantiomers for CYP2C9, 2C19, 3A4 and 3A5 was revealed. Analyses considering the clearance of only one or both enantiomers provided comparable enantiomer-enantiomer inhibition estimates. To conclude, this paper provides new insights into PZQ metabolic profile to enable a better understanding of enantioselective PK using substrate depletion-based methods. LC-MS/MS, ensuring the same final proportion of 25% (v/v) ACN for all samples. Calibration standard samples were prepared using a matrix consistent with experimental samples and were equally diluted. R-PZQ, S-PZQ and rac-PZQ were tested at 1.0 µM for CLint determination (N=3). Initial tests were performed to determine reaction linearity and protein binding effects. For the determination of the kinetic parameters, 10 concentrations log-scale distributed over a concentration range of 200-0.01 µM were used (N=2). Based on initial linearity experiments, measured time points were adjusted for rhCYP 1A2, 2C9, 2D6, 3A4, 3A5 to 0-5-10-20-30 min, for rhCYP 1A1 and 2C19 to 0-4-8-16-24 min; and for rhCYP 3A7 to 0-5-10-20-30-50-75 min. A selection of samples (1 and 10 µM, 0 and 30 min) were analyzed by LC-qTOF for metabolite profiling. For K i determination, R-PZQ and S-PZQ were incubated with selected rhCYPs in a 7 x 7 matrix ratio (N=2), at concentrations equivalent to 5, 2, 0.8, 0.32, 0.12, 0.05 and 0 K m values (where 0 K m are incubations with “substrate enantiomer” in the absence of “inhibitory enantiomer”). Parallel incubations with specific reference compounds for each CYP isoform were used as positive controls (1 µM, n=2), i.e. 7-ethoxycoumarin for CYP 1A1/2, efavirenz for CYP 2B6, amodiaquine for CYP 2C8, diclofenac for CYP 2C9, omeprazole for CYP 2C19, dextromethorphan for
Mechanisms underlying priapism in sickle cell disease: targeting and key innovations on the preclinical landscape

ABSTRACT Introduction: Priapism is prolonged penile erection in the absence of sexual arousal or desire and is a devastating condition affecting millions of patients with sickle cell disease (SCD) globally. Available drug treatments for SCD-related priapism remain limited and have been primarily reactive rather than preventive. Hence, there is an unmet need for new drug targets and pharmacologic therapies. Areas covered: We examine the molecular mechanisms underlying SCD-associated priapism evaluated mostly in animal models. In mouse models of SCD, molecular defects of priapism operating at the cavernous tissue level include reduced tonic NO/cGMP signaling, elevated oxidative/nitrosative stress, vascular adhesion molecule derangements, excessive adenosine and opiorphin signaling, dysregulated vasoconstrictive RhoA/ROCK signaling, and testosterone deficiency. We discuss the consequences of downregulated cGMP-dependent phosphodiesterase type 5 (PDE5) activity in response to these molecular signaling derangements, as the main effector mechanism causing unrestrained cavernous tissue relaxation that results in priapism. Expert opinion: Basic science studies are crucial for understanding the underlying pathophysiology of SCD-associated priapism. Understanding the molecular mechanisms could unearth new therapeutic targets for this condition based on these mechanisms. Treatment options should aim to improve deranged erection physiology regulatory signaling to prevent priapism and potentially restore or preserve erectile function.
Crohn's Disease Activity Quantified by Iodine Density Obtained From Dual-Energy Computed Tomography Enterography

Objective The objective of this study was to assess if bowel wall iodine density obtained from dual-source, dual-energy computed tomography enterography (DECTE) could be a biomarker of Crohn's disease activity. Methods Twenty-two patients with Crohn's disease imaged with DECTE from February 2016 to May 2018 were retrospectively identified by departmental report search. Iodine maps were created with commercial software (Syngovia). Iodine content was normalized to the aorta, and then manual dual-energy region-of-interest cursors were placed over the visibly assessed maximal and minimal iodine density within segments of involved as well as unaffected small bowel. The mixed Hounsfield unit value, maximum iodine density (Imax), and minimum iodine density (Imin) were recorded. The length of affected bowel demonstrating maximum disease activity as a percentage of overall involvement was subjectively assessed. A weighted iodine density (Iweighted) was calculated. The clinical assessment of disease activity using erythrocyte sedimentation rate, C-reactive protein, fecal calprotectin, colonoscopy/endoscopy, and surgery, if available, served as the reference standard. The Crohn's disease activity index was also used as a separate additional reference standard. Results Significant heterogeneity within the affected segments was present. The average Imax and Imin of affected bowel was 4.27 ± 1.11 (2.4–7.4) mg/mL and 2.71 ± 0.51 (2.2–3.9) mg/mL, respectively. Iodine density of normal-appearing small bowel was 1.40 ± 0.26 (0.9–1.9) mg/mL. The Imax and Imin of affected bowel differed significantly from normal bowel (P < 0.0001). Mixed Hounsfield unit (101.82 ± 27.5) also statistically differed (46.33 ± 19.62) (P < 0.0001). Using overall clinical assessment as the reference standard, all patients with Imin of greater than 2.6 mg/mL, Iweighted of greater than 3.3 mg/mL, or Imax of greater than 4.7 mg/mL had clinically active disease. Sixteen of 17 patients with Imin of greater than 2.2 mg/mL and 14/15 with Iweighted of greater than 3 mg/mL had clinically active disease. Using Crohn's disease activity index as the reference standard, all patients with Imin of greater than 2.7 mg/mL, Iweighted of greater than 3.6 mg/mL, or Imax of greater than 5.4 mg/mL had clinically active disease. The median effective dose was 4.64 ± 1.68 mSv (range, 2.03–8.12 mSv). Conclusions Iodine density obtained from DECTE highlights regions of maximal activity within affected bowel segments. An iodine density of 2 mg/mL appears to be a threshold between normal bowel segments and those with active Crohn's disease. Iodine density measurement thresholds Imin of greater than 2.6 mg/mL, Iweighted of greater than 3.3 mg/mL, and Imax of greater than 4.7 mg/mL correlate with established clinical markers of disease activity, with Imin seemingly most useful in daily clinical practice.
The Applicability of the New South Wales Quality Teaching Model to the Jordanian Primary School Context

هدفت الدراسة الحالية الى التحقق من مدى ملاءمة نموذج نيو ساوث ويلز لجودة التعليم لبيئة التعليم الابتدائي الأردني. كون طريقة البحث المستخدمة هي طريقة البحث النوعي، اقتصرت عينة الدراسة على سبع معلمين. لجمع بيانات البحث، استخدم الباحثان المقابلة والملاحظة وتحليل الوثائق. اشارت نتائج الدراسة إلى ان التعليم النوعي وصف بشكل متشابه في النموذج المشار اليه وكذلك في وثائق وزارة التربية والتعليم الأردنية. كذلك اشارت النتائج إلى ان معظم عناصر التعليم النوعي المشار اليها في النموذج كانت ظاهرة وواضحة داخل الغرف الصفية التي تمت ملاحظتها. بالرغم من هذا التشابه هناك فرق ما بين وزارة التربية والتعليم ونموذج نيو ساوث ويلز من جهة وبين المعلمين من جهة اخرى من حيث طريقة تفسير مفهوم معنى التعليم النوعي أو جودة التعليم.
Recent Applications of Three Dimensional Printing in Cardiovascular Medicine

Three dimensional (3D) printing, which consists in the conversion of digital images into a 3D physical model, is a promising and versatile field that, over the last decade, has experienced a rapid development in medicine. Cardiovascular medicine, in particular, is one of the fastest growing area for medical 3D printing. In this review, we firstly describe the major steps and the most common technologies used in the 3D printing process, then we present current applications of 3D printing with relevance to the cardiovascular field. The technology is more frequently used for the creation of anatomical 3D models useful for teaching, training, and procedural planning of complex surgical cases, as well as for facilitating communication with patients and their families. However, the most attractive and novel application of 3D printing in the last years is bioprinting, which holds the great potential to solve the ever-increasing crisis of organ shortage. In this review, we then present some of the 3D bioprinting strategies used for fabricating fully functional cardiovascular tissues, including myocardium, heart tissue patches, and heart valves. The implications of 3D bioprinting in drug discovery, development, and delivery systems are also briefly discussed, in terms of in vitro cardiovascular drug toxicity. Finally, we describe some applications of 3D printing in the development and testing of cardiovascular medical devices, and the current regulatory frameworks that apply to manufacturing and commercialization of 3D printed products.