Miracle-dz/UniFAR-FTUs huggingface dataset:
Prognostic analysis of hepatocellular carcinoma on the background of liver cirrhosis via contrast-enhanced ultrasound and pathology

The aim of this study was to analyze the correlation between the quantitative parameters of contrast-enhancement ultrasound for primary hepatocellular carcinoma (HCC) and biological manifestations of tumor (Ki-67), and to explore the related risk factors of primary hepatocellular carcinoma, so as to provide the theoretical basis for the further study on contrast-enhancement ultrasound manifestations, clinical features and prognosis of HCC. The patients with HCC confirmed by operation or puncture were collected, and those with the background of liver cirrhosis and immunohistochemical staining for tumor sample sections were selected. H&E staining sections of pathological tissues of tumor samples were observed, whether there was any microvessel invasion (MVI) was recorded, the microvessel density (MVD) was counted and the recurrence situations after liver cancer operation was followed up. The change in size of tumor at arterial phase in contrast-enhancement ultrasound, enhancement mode and form at arterial phase, and whether there were tortuous vessels inside or not, and the enhancement intensity, extinction time and extinction intensity at portal phase were observed. The relationship between the parameters of contrast-enhancement ultrasound and Ki-67, AFP, MVD, MVI, tissue differentiation degree of tumor samples and recurrence was analyzed. Under the background of liver cirrhosis, there were significant differences in different enhancement modes and quantification parameters of contrast-enhancement ultrasound for HCC with different expression of Ki-67. Those with obvious tumor enlargement, inhomogeneous enhancement at arterial phase and irregular enhancement form at arterial phase after contrast-enhancement ultrasound had a high incidence of positive Ki-67 and a high early recurrence rate. The inhomogeneous enhancement at arterial phase might predict the proliferative activity and recurrence time of tumor cells; irregular enhancement form at arterial phase might indicate tumor MVI; and the low enhancement of tumor at portal phase may predict a lower degree of tissue differentiation, a higher tumor malignancy and poor prognosis. The incidence of positive Ki-67 under the background of liver cirrhosis is high, indicating poor prognosis. The enhancement mode and parameters of contrast-enhancement ultrasound for HCC may help evaluate the clinical biological manifestations of HCC and predict the postoperative recurrence of HCC.
Mechanisms of Toxicity, Carcinogenesis, Cancer Prevention and Cancer Therapy

One of the major problems with treating cancer is that it is detected too late. Early lesions and transitions often occur ten to fifteen years prior to our ability to detect the disease by palpation or imaging. By the time many cancers are detected they have long since acquired the ability to generate micrometasases or populations of tumor cells that can develop drug resistance. Our best approach to treating or preventing cancer is early detection and an understanding of the earliest steps in the transition of normal cells to malignant ones. However, there are considerable obstacles to studying the early steps of cancer formation in vivo. For one, the multitude of random genetic aberrations that are generated during the carcinogenic process mask the specific non-random and mechanistically-related aberrations that would provide insights into how the lesion is initiated. Finding the critical alterations in a sea of changes is difficult. Furthermore, the premalignant lesions are small, sporadic and arise in a non-synchronized fashion, making detection difficult and analysis almost impossible. Finally, at the present time, these cells have not been successfully cultured in vitro. Our ignorance about the earliest molecular changes prevents studies that would identify individuals at risk or identify targets for prevention strategies. An in vitro model that mimics the transitions that occur as normal epithelial cells become malignant would provide major advances in several aspects of dealing with the disease. Early detection of lesions could be used for risk assessment and diagnosis of the disease at early stages. Additionally, and perhaps, the most significant advance would be the insights a model system may provide to the initiation of lesions and the transition of these lesions to malignancy allowing the translation of that information into preventive agents. It is for these reasons that we began studying human epithelial cells in vitro, focusing on mammary epithelial cells in particular. Recently, studies of human epithelial cells and fibroblasts from healthy individuals have been providing novel insights into how early epigenetic and genetic events affect genomic integrity and fuel carcinogenesis. Key epigenetic changes, such as the hypermethylation of the p16 promoter sequence, create a previously unappreciated pre-clonal phase of tumorigenesis in which a subpopulation of epithelial cells is positioned for progression to malignancy (Nature 409:636, 2001). These key changes generate epigenetic and genetic mosaicism, precede the clonal outgrowth of pre-malignant lesions and occur frequently in healthy, disease-free individuals (Caner Cell 5:263, 2004). Prior work from our laboratory has identified biomarkers that may be useful for risk assessment as well as provide targets for the elimination of these cells. Understanding more about these early events should provide novel molecular candidates for prevention and therapy of cancer.
Effect of Insulin Degludec vs Insulin Glargine U100 on Hypoglycemia in Patients With Type 1 Diabetes: The SWITCH 1 Randomized Clinical Trial

Importance Hypoglycemia, common in patients with type 1 diabetes, is a major barrier to achieving good glycemic control. Severe hypoglycemia can lead to coma or death. Objective To determine whether insulin degludec is noninferior or superior to insulin glargine U100 in reducing the rate of symptomatic hypoglycemic episodes. Design, Setting, and Participants Double-blind, randomized, crossover noninferiority trial involving 501 adults with at least 1 hypoglycemia risk factor treated at 84 US and 6 Polish centers (January 2014-January 12, 2016) for two 32-week treatment periods, each with a 16-week titration and a 16-week maintenance period. Interventions Patients were randomized 1:1 to receive once-daily insulin degludec followed by insulin glargine U100 (n = 249) or to receive insulin glargine U100 followed by insulin degludec (n = 252) and randomized 1:1 to morning or evening dosing within each treatment sequence. Main Outcomes and Measures The primary end point was the rate of overall severe or blood glucose-confirmed (<56 mg/dL) symptomatic hypoglycemic episodes during the maintenance period. Secondary end points included the rate of nocturnal symptomatic hypoglycemic episodes and proportion of patients with severe hypoglycemia during the maintenance period. The noninferiority criterion for the primary end point and for the secondary end point of nocturnal hypoglycemia was defined as an upper limit of the 2-sided 95% CI for a rate ratio of 1.10 or lower; if noninferiority was established, 2-sided statistical testing for superiority was conducted. Results Of the 501 patients randomized (mean age, 45.9 years; 53.7% men), 395 (78.8%) completed the trial. During the maintenance period, the rates of overall symptomatic hypoglycemia were 2200.9 episodes per 100 person-years’ exposure (PYE) in the insulin degludec group vs 2462.7 episodes per 100 PYE in the insulin glargine U100 group for a rate ratio (RR) of 0.89 (95% CI, 0.85-0.94; P < .001 for noninferiority; P < .001 for superiority; rate difference, −130.31 episodes per 100 PYE; 95% CI, −193.5 to −67.16). The rates of nocturnal symptomatic hypoglycemia were 277.1 per 100 PYE in the insulin degludec group vs 428.6 episodes per 100 PYE in the insulin glargine U100 group, for an RR of 0.64 (95% CI, 0.56-0.73; P < .001 for noninferiority; P < .001 for superiority; rate difference, −61.94 episodes per 100 PYE; 95% CI, −83.85 to −40.03). A lower proportion of patients in the insulin degludec than in the insulin glargine U100 group experienced severe hypoglycemia during the maintenance period (10.3%, 95% CI, 7.3%-13.3% vs 17.1%, 95% CI, 13.4%-20.8%, respectively; McNemar P = .002; risk difference, −6.8%; 95% CI, −10.8% to −2.7%). Conclusions and Relevance Among patients with type 1 diabetes and at least 1 risk factor for hypoglycemia, 32 weeks’ treatment with insulin degludec vs insulin glargine U100 resulted in a reduced rate of overall symptomatic hypoglycemic episodes. Trial Registration clinicaltrials.gov Identifier: NCT02034513
Boundary Control of Coupled Reaction-Advection-Diffusion Systems With Spatially-Varying Coefficients

Recently, the problem of boundary stabilization for unstable linear constant-coefficient coupled reaction-diffusion systems was solved by means of the backstepping method. The extension of this result to systems with advection terms and spatially-varying coefficients is challenging due to complex boundary conditions that appear in the equations verified by the control kernels. In this technical note we address this issue by showing that these equations are essentially equivalent to those verified by the control kernels for first-order hyperbolic coupled systems, which were recently found to be well-posed. The result therefore applies in this case, allowing us to prove $H^{1}$ stability for the closed-loop system. It also unveils a previously unknown connection between backstepping kernels for coupled parabolic and hyperbolic problems.
FcγRIIa defunctioning polymorphism in paediatric patients with renal allograft

Introduction Fc gamma receptor (FcγR) IIa is considered the most widely distributed of the three classes of Fc receptors, and it expresses an allelic polymorphism. This type of polymorphism may modify the immune response and may be an important factor for some diseases. The aim of the study reported herein was to evaluate the association between the FcγRIIa polymorphism and susceptibility to both end-stage renal disease (ESRD) and acute kidney graft rejection (AR) in children who have undergone renal transplantation. Material and methods The study evaluated 70 children who had undergone transplantation and 60 healthy subjects. AR was observed in 25 children. Results FcγRIIa genotypes and alleles were significantly different between transplantation patients and the control group. The assessment for FcγR of the groups in which AR was present showed that there was only a risk of having an acute rejection in homozygous genotype RR. Conclusions FcγRIIa RR genotype and allele frequency was increased in paediatric renal transplant recipients. The present findings showed that FcγRIIa genotype may be related to ESRD disease susceptibility, and FcγRIIa polymorphisms seemed to affect AR.
Mosquito bottlenecks alter viral mutant swarm in a tissue and time-dependent manner with contraction and expansion of variant positions and diversity

Abstract Viral diversity is theorized to play a significant role during virus infections, particularly for arthropod-borne viruses (arboviruses) that must infect both vertebrate and invertebrate hosts. To determine how viral diversity influences mosquito infection and dissemination Culex taeniopus mosquitoes were infected with the Venezuelan equine encephalitis virus endemic strain 68U201. Bodies and legs/wings of the mosquitoes were collected individually and subjected to multi-parallel sequencing. Virus sequence diversity was calculated for each tissue. Greater diversity was seen in mosquitoes with successful dissemination versus those with no dissemination. Diversity across time revealed that bottlenecks influence diversity following dissemination to the legs/wings, but levels of diversity are restored by Day 12 post-dissemination. Specific minority variants were repeatedly identified across the mosquito cohort, some in nearly every tissue and time point, suggesting that certain variants are important in mosquito infection and dissemination. This study demonstrates that the interaction between the mosquito and the virus results in changes in diversity and the mutational spectrum and may be essential for successful transition of the bottlenecks associated with arbovirus infection.
Mammalian target of rapamycin inhibition attenuates myocardial ischaemia–reperfusion injury in hypertrophic heart

Pathological cardiac hypertrophy aggravated myocardial infarction and is causally related to autophagy dysfunction and increased oxidative stress. Rapamycin is an inhibitor of serine/threonine kinase mammalian target of rapamycin (mTOR) involved in the regulation of autophagy as well as oxidative/nitrative stress. Here, we demonstrated that rapamycin ameliorates myocardial ischaemia reperfusion injury by rescuing the defective cytoprotective mechanisms in hypertrophic heart. Our results showed that chronic rapamycin treatment markedly reduced the phosphorylated mTOR and ribosomal protein S6 expression, but not Akt in both normal and aortic‐banded mice. Moreover, chronic rapamycin treatment significantly mitigated TAC‐induced autophagy dysfunction demonstrated by prompted Beclin‐1 activation, elevated LC3‐II/LC3‐I ratio and increased autophagosome abundance. Most importantly, we found that MI/R‐induced myocardial injury was markedly reduced by rapamycin treatment manifested by the inhibition of myocardial apoptosis, the reduction of myocardial infarct size and the improvement of cardiac function in hypertrophic heart. Mechanically, rapamycin reduced the MI/R‐induced iNOS/gp91phox protein expression and decreased the generation of NO and superoxide, as well as the cytotoxic peroxynitrite. Moreover, rapamycin significantly mitigated MI/R‐induced endoplasmic reticulum stress and mitochondrial impairment demonstrated by reduced Caspase‐12 activity, inhibited CHOP activation, decreased cytoplasmic Cyto‐C release and preserved intact mitochondria. In addition, inhibition of mTOR also enhanced the phosphorylated ERK and eNOS, and inactivated GSK3β, a pivotal downstream target of Akt and ERK signallings. Taken together, these results suggest that mTOR signalling protects against MI/R injury through autophagy induction and ERK‐mediated antioxidative and anti‐nitrative stress in mice with hypertrophic myocardium.
Kundt spacetimes

Kundt spacetimes are of great importance in general relativity in four dimensions and have a number of physical applications in higher dimensions in the context of string theory. The degenerate Kundt spacetimes have many special and unique mathematical properties, including their invariant curvature structure and their holonomy structure. We provide a rigorous geometrical kinematical definition of the general Kundt spacetime in four dimensions; essentially a Kundt spacetime is defined as one admitting a null vector that is geodesic, expansion-free, shear-free and twist-free. A Kundt spacetime is said to be degenerate if the preferred kinematic and curvature null frames are all aligned. The degenerate Kundt spacetimes are the only spacetimes in four dimensions that are not -non-degenerate, so that they are not determined by their scalar polynomial curvature invariants. We first discuss the non-aligned Kundt spacetimes, and then turn our attention to the degenerate Kundt spacetimes. The degenerate Kundt spacetimes are classified algebraically by the Riemann tensor and its covariant derivatives in the aligned kinematic frame; as an example, we classify Riemann type D degenerate Kundt spacetimes in which ∇(Riem), ∇(2)(Riem) are also of type D. We discuss other local characteristics of the degenerate Kundt spacetimes. Finally, we discuss degenerate Kundt spacetimes in higher dimensions.
Verification, validation and sensitivity studies in computational biomechanics

Computational techniques and software for the analysis of problems in mechanics have naturally moved from their origins in the traditional engineering disciplines to the study of cell, tissue and organ biomechanics. Increasingly complex models have been developed to describe and predict the mechanical behavior of such biological systems. While the availability of advanced computational tools has led to exciting research advances in the field, the utility of these models is often the subject of criticism due to inadequate model verification and validation (V&V). The objective of this review is to present the concepts of verification, validation and sensitivity studies with regard to the construction, analysis and interpretation of models in computational biomechanics. Specific examples from the field are discussed. It is hoped that this review will serve as a guide to the use of V&V principles in the field of computational biomechanics, thereby improving the peer acceptance of studies that use computational modeling techniques.
Variational Inference: A Review for Statisticians

ABSTRACT One of the core problems of modern statistics is to approximate difficult-to-compute probability densities. This problem is especially important in Bayesian statistics, which frames all inference about unknown quantities as a calculation involving the posterior density. In this article, we review variational inference (VI), a method from machine learning that approximates probability densities through optimization. VI has been used in many applications and tends to be faster than classical methods, such as Markov chain Monte Carlo sampling. The idea behind VI is to first posit a family of densities and then to find a member of that family which is close to the target density. Closeness is measured by Kullback–Leibler divergence. We review the ideas behind mean-field variational inference, discuss the special case of VI applied to exponential family models, present a full example with a Bayesian mixture of Gaussians, and derive a variant that uses stochastic optimization to scale up to massive data. We discuss modern research in VI and highlight important open problems. VI is powerful, but it is not yet well understood. Our hope in writing this article is to catalyze statistical research on this class of algorithms. Supplementary materials for this article are available online.
Phytosphingosine Prevents the Formation of Young Salivary Biofilms in vitro

Dental biofilms are formed in a multistep process that is initiated by the adhesion of oral bacteria to the dental hard surface. As dental biofilms are associated with oral diseases their control is necessary in order to maintain oral health. Recently, it was revealed that phytosphingosine (PHS)-treated hydroxyapatite discs showed anti-adhesive activity in a static in vitro biofilm model against Streptococcus mutans. The goal of the present study was to further unravel the anti-adhesive and anti-biofilm properties of PHS in both static and dynamic in vitro biofilm models against a full salivary inoculum. After 3 h under static conditions, bacterial adherence on PHS-treated cover glass slides was reduced by 60% compared to the untreated surface. After 6 and 24 h under static conditions, no significant differences in bacterial adherence were observed between PHS-treated and untreated cover glass slides. However, under dynamic conditions, i.e., the presence of shear forces, virtually no bacterial adherence was observed for up to 16 h on PHS-coated surfaces. Besides, PHS showed a strong bactericidal activity on salivary biofilms. Treatment of a 3- and 6-h statically grown biofilm resulted in a 99 and 94% reduction of viable cells, respectively, which was effectuated within minutes. In principle, these anti-adherence and anti-biofilm properties make PHS a promising candidate ingredient for use in oral care products aimed at oral microbial control.
Diagnostic Accuracy of Pediatric Teledermatology Using Parent-Submitted Photographs: A Randomized Clinical Trial

Importance Advances in smartphone photography (both quality and image transmission) may improve access to care via direct parent-to-clinician telemedicine. However, the accuracy of diagnoses that are reliant on parent-provided photographs has not been formally compared with diagnoses made in person. Objective To assess whether smartphone photographs of pediatric skin conditions taken by parents are of sufficient quality to permit accurate diagnosis. Design, Setting, and Participants A prospective study was conducted among 40 patient-parent dyads at a pediatric dermatology clinic at the Children’s Hospital of Philadelphia from March 1 to September 30, 2016, to assess concordance between diagnoses made by an independent pediatric dermatologist based on in-person examination and those based on parental photographs. Half of the patient-parent dyads were randomized for a secondary analysis to receive instructions on how best to take photographs with smartphones. Clinicians were blinded to whether parents had received photography instructions. Exposures Half of the patient-parent dyads received a simple, 3-step instruction sheet on how best to take photographs using a smartphone (intervention group); the other half did not (control group). Main Outcomes and Measures Concordance between photograph-based vs in-person diagnosis in the intervention vs control groups, as quantified using Cohen &kgr;, a measure of interrater agreement that takes into account the possibility of agreement occurring by chance. Results Among the 40 patient-parent dyads (22 female children and 18 male children; mean [SD] age, 6.96 [5.23] years), overall concordance between photograph-based vs in-person diagnosis was 83% (95% CI, 71%-94%; &kgr; = 0.81). Diagnostic concordance was 89% (95% CI, 75%-97%; &kgr; = 0.88) in a subgroup of 37 participants with photographs considered of high enough quality to make a diagnosis. No statistically significant effect of photography instructions on concordance was detected (group that received instructions, 85%; group that did not receive instructions, 80%; P = .68). In cases of diagnostic disagreement, appropriate follow-up was suggested. Conclusions and Relevance Parent-operated smartphone photography can accurately be used as a method to provide pediatric dermatologic care. Trial Registration clinicaltrials.gov Identifier: NCT03246945
Exposure to the World Trade Center Disaster and 9/11-Related Post-Traumatic Stress Disorder and Household Disaster Preparedness

Abstract Objective In a population with prior exposure to the World Trade Center disaster, this study sought to determine the subsequent level of preparedness for a new disaster and how preparedness varied with population characteristics that are both disaster-related and non-disaster-related. Methods The sample included 4496 World Trade Center Health Registry enrollees who completed the Wave 3 (2011-2012) and Hurricane Sandy (2013) surveys. Participants were considered prepared if they reported possessing at least 7 of 8 standard preparedness items. Logistic regression was used to determine associations between preparedness and demographic and medical factors, 9/11-related post-traumatic stress disorder (PTSD) assessed at Wave 3, 9/11 exposure, and social support. Results Over one-third (37.5%) of participants were prepared with 18.8% possessing all 8 items. The item most often missing was an evacuation plan (69.8%). Higher levels of social support were associated with being prepared. High levels of 9/11 exposure were associated with being prepared in both the PTSD and non-PTSD subgroups. Conclusions Our findings indicate that prior 9/11 exposure favorably impacted Hurricane Sandy preparedness. Future preparedness messaging should target people with low social support networks. Communications should include information on evacuation zones and where to find information about how to evacuate. (Disaster Med Public Health Preparedness. 2015;9:625–633)