Miracle-dz/UniFAR-FTUs huggingface dataset:
Head motion during cone-beam computed tomography: Analysis of frequency and influence on image quality

Purpose Image artifacts caused by patient motion cause problems in cone-beam computed tomography (CBCT) because they lead to distortion of the 3-dimensional reconstruction. This prospective study was performed to quantify patient movement during CBCT acquisition and its influence on image quality. Materials and Methods In total, 412 patients receiving CBCT imaging were equipped with a wireless head sensor system that detected inertial, gyroscopic, and magnetometric movements with 6 dimensions of freedom. The type and amplitude of movements during CBCT acquisition were evaluated and image quality was rated in 7 different anatomical regions of interest. For continuous variables, significance was calculated using the Student t-test. A linear regression model was applied to identify associations of the type and extent of motion with image quality scores. Kappa statistics were used to assess intra- and inter-rater agreement. Chi-square testing was used to analyze the impact of age and sex on head movement. Results All CBCT images were acquired in a 10-month period. In 24% of the investigations, movement was recorded (acceleration: >0.10 [m/s2]; angular velocity: >0.018 [°/s]). In all examined regions of interest, head motion during CBCT acquisition resulted in significant impairment of image quality (P<0.001). Movement in the horizontal and vertical axes was most relevant for image quality (R2>0.7). Conclusion Relevant head motions during CBCT imaging were frequently detected, leading to image quality loss and potentially impairing diagnosis and therapy planning. The presented data illustrate the need for digital correction algorithms and hardware to minimize motion artefacts in CBCT imaging.
Detection of COVID-19 Using Deep Learning Algorithms on Chest Radiographs

Purpose: To evaluate the performance of a deep learning (DL) algorithm for the detection of COVID-19 on chest radiographs (CXR). Materials and Methods: In this retrospective study, a DL model was trained on 112,120 CXR images with 14 labeled classifiers (ChestX-ray14) and fine-tuned using initial CXR on hospital admission of 509 patients, who had undergone COVID-19 reverse transcriptase-polymerase chain reaction (RT-PCR). The test set consisted of a CXR on presentation of 248 individuals suspected of COVID-19 pneumonia between February 16 and March 3, 2020 from 4 centers (72 RT-PCR positives and 176 RT-PCR negatives). The CXR were independently reviewed by 3 radiologists and using the DL algorithm. Diagnostic performance was compared with radiologists’ performance and was assessed by area under the receiver operating characteristics (AUC). Results: The median age of the subjects in the test set was 61 (interquartile range: 39 to 79) years (51% male). The DL algorithm achieved an AUC of 0.81, sensitivity of 0.85, and specificity of 0.72 in detecting COVID-19 using RT-PCR as the reference standard. On subgroup analyses, the model achieved an AUC of 0.79, sensitivity of 0.80, and specificity of 0.74 in detecting COVID-19 in patients presented with fever or respiratory systems and an AUC of 0.87, sensitivity of 0.85, and specificity of 0.81 in distinguishing COVID-19 from other forms of pneumonia. The algorithm significantly outperforms human readers (P<0.001 using DeLong test) with higher sensitivity (P=0.01 using McNemar test). Conclusions: A DL algorithm (COV19NET) for the detection of COVID-19 on chest radiographs can potentially be an effective tool in triaging patients, particularly in resource-stretched health-care systems.
How to Improve the Antioxidant Defense in Asphyxiated Newborns—Lessons from Animal Models

Oxygen free radicals have been implicated in brain damage after neonatal asphyxia. In the early phase of asphyxia/reoxygenation, changes in antioxidant enzyme activity play a pivotal role in switching on and off the cascade of events that can kill the neurons. Hypoxia/ischemia (H/I) forces the brain to activate endogenous mechanisms (e.g., antioxidant enzymes) to compensate for the lost or broken neural circuits. It is important to evaluate therapies to enhance the self-protective capacity of the brain. In animal models, decreased body temperature during neonatal asphyxia has been shown to increase cerebral antioxidant capacity. However, in preterm or severely asphyxiated newborns this therapy, rather than beneficial seems to be harmful. Thus, seeking new therapeutic approaches to prevent anoxia-induced complications is crucial. Pharmacotherapy with deferoxamine (DFO) is commonly recognized as a beneficial regimen for H/I insult. DFO, via iron chelation, reduces oxidative stress. It also assures an optimal antioxidant protection minimizing depletion of the antioxidant enzymes as well as low molecular antioxidants. In the present review, some aspects of recently acquired insight into the therapeutic effects of hypothermia and DFO in promoting neuronal survival after H/I are discussed.
Thyroid hormone receptor α in skeletal muscle is essential for T3‐mediated increase in energy expenditure

Thyroid hormones are important for homeostatic control of energy metabolism and body temperature. Although skeletal muscle is considered a key site for thyroid action, the contribution of thyroid hormone receptor signaling in muscle to whole‐body energy metabolism and body temperature has not been resolved. Here, we show that T3‐induced increase in energy expenditure requires thyroid hormone receptor alpha 1 (TRα1) in skeletal muscle, but that T3‐mediated elevation in body temperature is achieved in the absence of muscle‐TRα1. In slow‐twitch soleus muscle, loss‐of‐function of TRα1 (TRαHSACre) alters the fiber‐type composition toward a more oxidative phenotype. The change in fiber‐type composition, however, does not influence the running capacity or motivation to run. RNA‐sequencing of soleus muscle from WT mice and TRαHSACre mice revealed differentiated transcriptional regulation of genes associated with muscle thermogenesis, such as sarcolipin and UCP3, providing molecular clues pertaining to the mechanistic underpinnings of TRα1‐linked control of whole‐body metabolic rate. Together, this work establishes a fundamental role for skeletal muscle in T3‐stimulated increase in whole‐body energy expenditure.
Effects of Neuronic Shutter Observed in the EEG Alpha Rhythm

Abstract The posterior alpha (α) rhythm, seen in human electroencephalogram (EEG), is posited to originate from cycling inhibitory/excitatory states of visual relay cells in the thalamus. These cycling states are thought to lead to oscillating visual sensitivity levels termed the “neuronic shutter effect. ” If true, perceptual performance should be predictable by observed α phase (of cycling inhibitory/excitatory states) relative to the timeline of afferentiation onto the visual cortex. Here, we tested this hypothesis by presenting contrast changes at near perceptual threshold intensity through closed eyelids to 20 participants (balanced for gender) during times of spontaneous α oscillations. To more accurately and rigorously test the shutter hypothesis than ever before, α rhythm phase and amplitude were calculated relative to each individual’s retina-to-primary visual cortex (V1) conduction delay, estimated from the individual’s C1 visual-evoked potential (VEP) latency. Our results show that stimulus observation rates (ORs) are greater at a trough than a peak of the posterior α rhythm when phase is measured at the individual’s conduction delay relative to stimulus onset. Specifically, the optimal phase for stimulus observation was found to be 272.41°, where ORs are 20.96% greater than the opposing phase of 92.41°. The perception-phase relationship is modulated by α rhythm amplitude and is not observed at lower amplitude oscillations. Collectively, these results provide support to the “neuronic shutter” hypothesis and demonstrate a phase and timing relationship consistent with the theory that cycling excitability in the thalamic relay cells underly posterior α oscillations.
Immunization with dendritic cells loaded with α-galactosylceramide at priming phase, but not at boosting phase, enhances cytotoxic T-lymphocyte activity against infection by intracellular bacteria

We evaluated the effect of immunization with dendritic cells (DCs) pulsed with a galactosylceramide ( a GalCer) and listeriolysin O (LLO) 91-99 peptide, a dominant cytotoxic T lymphocyte (CTL) epitope of Listeria monocytogenes by observing the responses of speciﬁc CD8 1 T cells and in vivo CTL activity. DCs were pulsed with various combinations of a GalCer and LLO91-99 peptide and administered to BALB/c mice. Immunization with DCs pulsed with a GalCer and LLO91-99 at priming phase and with DCs pulsed with LLO91-99 alone at boosting phase induced stronger in vivo CTL activity, reduced the bacterial load in spleens of Listeria challenged mice and augmented CD62L 1 CD8 1 central memory T cells compared with other immunization protocols. The blockade of interferon- g (IFN- g ) at boosting phase reversed the induction of CD8 1 central memory T cells and reduced the bacterial load in spleens of Listeria -challenged mice immunized with DCs pulsed with a GalCer and LLO91-99 at both phases, suggesting that a GalCer at boosting phase has deleterious effects through IFN- g production. These results indicate that immunization with DCs pulsed with CTL epitope peptide together with a GalCer at priming phase, but not at boosting phase, is feasible for eliciting a speciﬁc CTL activity and protective immunity against infection of intracellular bacteria.
Idelalisib Rescues Natural Killer Cells from Monocyte-Induced Immunosuppression by Inhibiting NOX2-Derived Reactive Oxygen Species

Idelalisib, a PI3Kδ inhibitor, inhibits antibody-induced formation of ROS in human monocytes by preventing Akt-dependent phosphorylation of NOX2. By rescuing NK cells from immunosuppressive ROS, idelalisib promotes NK cell–mediated antibody-dependent cellular cytotoxicity against malignant B cells. The phosphatidylinositol-4,5-bisphosphate-3 kinase-δ (PI3Kδ) inhibitor idelalisib, used alone or in combination with anti-CD20, is clinically efficacious in B-cell lymphoma and chronic lymphocytic leukemia (CLL) by promoting apoptosis of malignant B cells. PI3K regulates the formation of reactive oxygen species (ROS) by the myeloid NADPH oxidase NOX2, but the role of PI3Kδ in myeloid cell–induced immunosuppression is unexplored. We assessed the effects of idelalisib on the spontaneous and IgG antibody–induced ROS production by human monocytes, on ROS-induced cell death of human natural killer (NK) cells, and on tumor cell clearance in an NK cell–dependent mouse model of metastasis. Idelalisib potently and efficiently inhibited the formation of NOX2-derived ROS from monocytes and rescued NK cells from ROS-induced cell death. Idelalisib also promoted NK cell cytotoxicity against anti–CD20-coated primary human CLL cells and cultured malignant B cells. Experiments using multiple PI3K inhibitors implicated the PI3Kδ isoform in regulating NOX2-induced ROS formation and immunosuppression. In B6 mice, systemic treatment with idelalisib significantly reduced the formation of lung metastases from intravenously injected melanoma cells but did not affect metastasis in B6.129S6-Cybbtm1Din (Nox2−/−) mice or in NK cell–deficient mice. Our results imply that idelalisib rescues NK cells from NOX2/ROS-dependent immunosuppression and thus exerts antineoplastic efficacy beyond B-cell inhibition.
Rice stripe virus coat protein induces the accumulation of jasmonic acid, activating plant defence against the virus while also attracting its vector to feed

Abstract The jasmonic acid (JA) pathway plays crucial roles in plant defence against pathogens and herbivores. Rice stripe virus (RSV) is the type member of the genus Tenuivirus. It is transmitted by the small brown planthopper (SBPH) and causes damaging epidemics in East Asia. The role(s) that JA may play in the tripartite interaction against RSV, its host, and vector are poorly understood. Here, we found that the JA pathway was induced by RSV infection and played a defence role against RSV. The coat protein (CP) was the major viral component responsible for inducing the JA pathway. Methyl jasmonate treatment attracted SBPHs to feed on rice plants while a JA‐deficient mutant was less attractive than wild‐type rice. SBPHs showed an obvious preference for feeding on transgenic rice lines expressing RSV CP. Our results demonstrate that CP is an inducer of the JA pathway that activates plant defence against RSV while also attracting SBPHs to feed and benefitting viral transmission. This is the first report of the function of JA in the tripartite interaction between RSV, its host, and its vector.
Premarital Counseling Practices among Christian and Muslim Lay Counselors in Ghana

We examined premarital counseling services offered by Christian and Muslim lay counselors in Ghana. Participants including clergy, Islamic clerics, and laity practicing in four urban centers were interviewed. Thematic analysis showed that common issues covered include medical screening, beliefs and values, expectations, partner knowledge, roles and duties, sex, parenthood, financial management, communication, and conflicts. The findings offer important insight into religious premarital counseling in Ghana and contribute to the global literature on premarital counseling.
The Efficacy of Lasmiditan for the Treatment of Migraine: A Meta-Analysis of Randomized Controlled Studies

Introduction The efficacy of lasmiditan is used to alleviate migraine. We conduct a systematic review and meta-analysis to explore the influence of lasmiditan versus placebo on pain control in patients with migraine. Methods We search the PubMed, EMbase, Web of science, EBSCO, and Cochrane library databases through June 2020 for randomized controlled trials (RCTs) assessing the effect of lasmiditan versus placebo on pain control in patients with migraine. This meta-analysis was performed using the random effects model. Results Four randomized controlled trials are included in the meta-analysis. Overall, compared with the control group, in patients with migraine, lasmiditan treatment shows positive impact on pain free at 2 hours [risk ratio (RR), 1.74; 95% confidence interval (CI), 1.47–2.07; P < 0.00001], headache response at 2 hours (RR, 1.38; 95% CI, 1.28–1.49; P < 0.00001), pain free at 24 hours (RR, 1.55; 95% CI, 1.16–2.07; P = 0.003), and no or mild disability level (RR, 1.20; 95% CI, 1.11–1.29; P < 0.00001), but has no obvious influence on nausea (RR, 2.22; 95% CI, 0.92–5.35; P = 0.08). In addition, lasmiditan seems to result in the increase in dizziness (RR, 6.36; 95% CI, 3.00–13.46; P < 0.0001) and paresthesia (RR, 5.10; 95% CI, 2.66–9.78; P < 0.00001). Conclusions Lasmiditan treatment provides additional benefits for pain control in patients with migraine.
Omega-3 fatty acids plus vitamin for women with gestational diabetes or prediabetes: a meta-analysis of randomized controlled studies

Abstract Introduction Omega-3 fatty acids plus vitamin (e.g. vitamin D and E) may be beneficial to treat gestational diabetes mellitus (GDM), and we aimed to study the influence of omega-3 fatty acids plus vitamin versus placebo on the treatment efficacy of GDM. Methods We searched the databases including PubMed, Embase, and the Cochrane Central Register of Controlled Trials, and randomized controlled trials (RCTs) assessing the influence of omega-3 fatty acids and vitamins combination supplementation versus placebo on metabolic status of GDM were included. Results Five RCTs were included in the meta-analysis. Compared with control intervention for women with GDM or prediabetes, omega-3 fatty acids plus vitamin substantially reduced fasting plasma glucose (FPG, mean difference [MD] = –11.25; 95% confidence intervals [CI] = –13.73 to −8.77; p < .00001), insulin (MD=–6.16; 95% CI=–7.92 to −4.39; p < .00001), homeostasis model of assessment-insulin resistance (HOMA-IR, MD = 173.51; 95% CI = 164.72 to 182.30; p < .00001) and triglycerides (MD = 173.51; 95% CI = 164.72 to 182.30; p < .00001), as well as increased total antioxidant capacity (TAC, MD = 173.51; 95% CI = 164.72 to 182.30; p < .00001), but revealed no significant impact on total cholesterol (MD = 173.51; 95% CI = 164.72 to 182.30; p < .00001), low‑density lipoprotein cholesterol (LDL-C, MD = 173.51; 95% CI = 164.72 to 182.30; p < .00001), preterm delivery (OR = 173.51; 95% CI = 164.72 to 182.30; p < .00001) or macrosomia > 4000 g (OR = 173.51; 95% CI = 164.72 to 182.30; p < .00001). Conclusions The supplementation of omega-3 fatty acids in combination with vitamin D or E can improve glycemic control, alleviate oxidative stress, and reduce triglycerides, but had no effects on total cholesterol, preterm delivery or macrosomia > 4000 g in women with GDM or prediabetes.
Mass Spectrometry Imaging for Reliable and Fast Classification of Non-Small Cell Lung Cancer Subtypes

Simple Summary Diagnostic subtyping of non-small cell lung cancer is paramount for therapy stratification. Our study shows that the subtyping into pulmonary adenocarcinoma and pulmonary squamous cell carcinoma by mass spectrometry imaging is rapid and accurate using limited tissue material. Abstract Subtyping of non-small cell lung cancer (NSCLC) is paramount for therapy stratification. In this study, we analyzed the largest NSCLC cohort by mass spectrometry imaging (MSI) to date. We sought to test different classification algorithms and to validate results obtained in smaller patient cohorts. Tissue microarrays (TMAs) from including adenocarcinoma (ADC, n = 499) and squamous cell carcinoma (SqCC, n = 440), were analyzed. Linear discriminant analysis, support vector machine, and random forest (RF) were applied using samples randomly assigned for training (66%) and validation (33%). The m/z species most relevant for the classification were identified by on-tissue tandem mass spectrometry and validated by immunohistochemistry (IHC). Measurements from multiple TMAs were comparable using standardized protocols. RF yielded the best classification results. The classification accuracy decreased after including less than six of the most relevant m/z species. The sensitivity and specificity of MSI in the validation cohort were 92.9% and 89.3%, comparable to IHC. The most important protein for the discrimination of both tumors was cytokeratin 5. We investigated the largest NSCLC cohort by MSI to date and found that the classification of NSCLC into ADC and SqCC is possible with high accuracy using a limited set of m/z species.
Trichostatin A regulates fibro/adipogenic progenitor adipogenesis epigenetically and reduces rotator cuff muscle fatty infiltration

Rotator cuff (RC) muscle fatty infiltration (FI) is an important factor that determines the clinical outcome of patients with RC repair. There is no effective treatment for RC muscle FI at this time. The goal of this study is to define the role Trichostatin A (TSA), a histone deacetylase (HDAC) inhibitor in regulating muscle fibro/adipogenic progenitors (FAPs) adipogenesis and treating muscle fatty degeneration after massive RC tears in a mouse model. We hypothesize that TSA reduces muscle FI after massive RC tears. HDAC activity was measured in FAPs in RC muscle after tendon/nerve transection or sham surgery. FAPs were treated with TSA for 2 weeks and FAP adipogenesis was evaluated with perilipin and Oil Red O staining, as well as reverse transcript‐polymerase chain reaction for adipogenesis‐related genes. About 0.5 mg/kg TSA or dimethyl sulfoxide was administered to C57B/L6 mice with massive rotator cuff tears through daily intraperitoneal injection for 6 weeks. Supraspinatus muscles were harvested for biochemical and histology analysis. We found that FAPs showed significantly higher HDAC activity after RC tendon/nerve transection. TSA treatment significantly reduced HDAC activity and inhibited adipogenesis of FAPs. TSA also abolished the role of bone morphogenetic protein‐7 in inducing FAP adipogenesis and promoted FAP brown/beige adipose tissue (BAT) differentiation. TSA injection significantly increased histone H3 acetylation and reduced FI of rotator cuff muscles after massive tendon tears. Results from this study showed that TSA can regulate FAP adipogenesis and promote FAP BAT differentiation epigenetically. HDAC inhibition may be a new treatment strategy to reduce muscle FI after RC tears and repair.
Mountain Pine Beetle (MPB; Dendroctonus ponderosae) Pheromone Component Biosynthesis, Cytochromes P450 and Monoterpene Metabolism in Bark Beetles

Bark beetles successfully attack host trees by metabolizing host monterpenes efficiently and producing aggregation pheromones. Investigating enzymes involved in pheromone biosynthesis and monoterpene metabolism may identify unique molecular targets and provide information for developing new means to deal with bark beetle infestations. The three major mountain pine beetle (MPB, Dendroctonus ponderosae) pheromone components are frontalin, exo-brevicomin and trans-verbenol. Although these components were identified several decades ago, none of their biosynthetic pathways are known in detail and none of the involved enzymes are identified or characterized. This dissertation explores biochemical details of two important MPB pheromone components: exo-brevicomin and trans-verbenol, and bark beetle monoterpene metabolism in the context of specific enzymes. In vivo assays revealed that exo-brevicomin was predominantly produced in male fat bodies, and not in other tissues or by females, and that fat bodies catalyzed the conversion of decanoic acid to nonen-2-one, confirming that (6Z)-non-6-en-2-one is likely derived from fatty acid. Fat bodies converted (6Z)-non-6-en-2-one to 6,7epoxynonan-2-one, the direct precursor of exo-brevicomin, and (6Z)-non-6-en-2-ol. The epoxide was stable under physiological conditions. These results implicate a cytochrome P450 and cyclase in the terminal steps of exo-brevicomin biosynthesis and (6Z)-non-6-en-2-ol may be the precursor of (6Z)-non-6-en-2-one. Two novel enzymes are implicated in exo-brevicomin production: a cytochrome P450, CYP6CR1, and a novel short chain dehydrogenase, ZnoDH. Their mRNA profiles were consistent with exo-brevicomin production suggests their coordinate regulation.
New soluble angiopoietin analog of Hepta‐ANG1 prevents pathological vascular leakage

Vascular leak is a key driver of organ injury in diseases, and strategies that reduce enhanced permeability and vascular inflammation are promising therapeutic targets. Activation of the angiopoietin‐1 (ANG1)‐Tie2 tyrosine kinase signaling pathway is an important regulator of vascular quiescence. Here we describe the design and construction of a new soluble ANG1 mimetic that is a potent activator of endothelial Tie2 in vitro and in vivo. Using a chimeric fusion strategy, we replaced the extracellular matrix (ECM) binding and oligomerization domain of ANG1 with a heptameric scaffold derived from the C‐terminus of serum complement protein C4‐binding protein α. We refer to this new fusion protein biologic as Hepta‐ANG1, which forms a stable heptamer and induces Tie2 phosphorylation in cultured cells, and in the lung following intravenous injection of mice. Injection of Hepta‐ANG1 ameliorates vascular endothelial growth factor‐ and lipopolysaccharide‐induced vascular leakage, in keeping with the known functions of Angpt1‐Tie2 in maintaining quiescent vascular stability. The new Hepta‐ANG1 fusion is easy to produce and displays remarkable stability with high multimericity that can potently activate Tie2. It could be a new candidate ANG1 mimetic therapy for treatments of inflammatory vascular leak, such as acute respiratory distress syndrome and sepsis.