Miracle-dz/UniFAR-FTUs huggingface dataset:
The role of immunohistochemistry in subclassification of diffuse large B-cell lymphoma with a vague nodular pattern

Background The aim of the current study was to elucidate the histology, immunophenotype, and differential diagnosis of diffuse large B-cell lymphoma (DLBCL) with a vague nodular pattern. The heterogeneity of DLBCL is widely acknowledged. T-cell/histiocyte-rich B-cell lymphoma (T/HRBCL) is an uncommon aggressive variant of DLBCL. It has both nodal and extranodal presentation. The diagnosis of T/HRBCL is difficult as it may share several morphological and immunophenotypic similarities to other lymphoid diseases, such as nodular lymphocytic predominance Hodgkin’s lymphoma (NLPHL) and classic Hodgkin’s lymphoma. Thus, histologic subclassification of DLBCL is useful to avoid the risk of treatment failure. Accurate diagnosis therefore requires a careful immunohistochemical analysis. Patients and methods A total of 332 cases diagnosed with DLBCL with vague nodularity were reviewed between 2009 and 2012. They were reclassified as DLBCL, T/HRBCL, or NLPHL according to the 2008 WHO classification of lymphoid neoplasms. Immunohistochemical studies were carried out on paraffin-embedded tissue to study the immunophenotype of the large neoplatic cells (CD20, CD15, CD30, EMA, Bcl-2) and the background of non-neoplastic cells (CD3, CD20). Results In total, 332 cases diagnosed with DLBCL with vague nodularity were reviewed. Of which 318 (95.7%) cases were diagnosed as DLBCL, whereas 12 (3.6%) were reclassified as T/HRBCL and two (0.6%) were reclassified as NLPHL. There was male predominance (75.0%) among cases of T/HRBCL. Most patients with T/HRBCL were diagnosed at a younger age in comparison with patients with DLBCL, with a mean age of 46.50±14.2 years. Cervical lymph nodes were the most frequently involved lymph node type in both DLBCL (56.6%) or in T/HRBCL (50.0%). In terms of disease stage, there was a statistically significant difference (P=0.031) between T/HRBCL and DLBCL patients. Most patients [eight (66.7%)] with T/HRBCL presented at an advanced stage. All patients with DLBCL were CD3− and showed a diffuse positive reaction for CD20. However, patients with T/HRBCL showed a positive reaction for CD3 in 80–90% of the reactive cells and showed a positive reaction for CD20 in 10–20% of the large neoplastic cells. In NLPHL cases, lymphocytic and/or histiocytic cells showed positivity for EMA and CD20 and were surrounded by reactive T cells positive for CD3. There was a statistically significant difference between patients with T/HRBCL and DLBCL in the mean Bcl-2 expression (16.3±7.1 and 43.2±18.2, respectively). Conclusion T/HRBCL is an uncommon clinicopathologic subtype of DLBCL. Careful attention must be paid at the time of diagnosis because it may be confused with other lymphoid neoplasms characterized by a marked host immune reaction such as Hodgkin’s disease (NLPHL). Immunophenotyping analysis is essential in establishing the diagnosis of T/HRBCL in all cases.
Increased activation of the fear neurocircuitry in children exposed to violence

Most studies investigating the effect of childhood trauma on the brain are retrospective and mainly focus on maltreatment, whereas different types of trauma exposure such as growing up in a violent neighborhood, as well as developmental stage, could have differential effects on brain structure and function. The current magnetic resonance imaging study assessed the effect of trauma exposure broadly and violence exposure more specifically, as well as developmental stage on the fear neurocircuitry in 8‐ to 14‐year‐old children and adolescents (N = 69). We observed reduced hippocampal and increased amygdala volume with increasing levels of trauma exposure. Second, higher levels of violence exposure were associated with increased activation in the amygdala, hippocampus, and ventromedial prefrontal cortex during emotional response inhibition. This association was specifically observed in children younger than 10 years. Finally, increased functional connectivity between the amygdala and brainstem was associated with higher levels of violence exposure. Based on the current findings, it could be hypothesized that trauma exposure during childhood results in structural changes that are associated with later risk for psychiatric disorders. At the same time, it could be postulated that growing up in an unsafe environment leads the brain to functionally adapt to this situation in a way that promotes survival, where the long‐term costs or consequences of these adaptations are largely unknown and an area for future investigations.
The MicroRNA397b-LACCASE2 Module Regulates Root Lignification under Water and Phosphate Deficiency1

A negative regulator of lignin deposition in root vascular tissue is post-transcriptionally regulated during water and phosphate limitation. Deficiency of water and phosphate induce lignin deposition in roots. LACCASEs, a family of cell wall-localized multicopper oxidases, are involved in lignin biosynthesis. We demonstrate here that LACCASE2 (LAC2) acts as a negative regulator of lignin deposition in root vascular tissues during water deficit. An Arabidopsis (Arabidopsis thaliana) transfer DNA insertion mutant of LAC2 displayed a short primary root and high lignin deposition in root vascular tissues. However, restoration of LAC2 expression rescued these phenotypes. LAC2 expression was significantly down-regulated under water deficit and posttranscriptionally regulated by microRNA397b (miR397b) in roots under normal and water-deficit conditions. Down-regulation of miR397b activity increased LAC2 expression and root length, and decreased lignin content in root vasculature. Similarly, phosphate (Pi) deficiency inversely affected miR397b and LAC2 expression. Lignin deposition in the root elongation zone under Pi-limited conditions was dependent on LAC2 expression. Localized iron accumulation and callose deposition in the root elongation zone under Pi deficiency increased with LAC2-dependent lignification, suggesting a direct relationship between these processes. Our study reveals a regulatory role for the miR397b-LAC2 module in root lignification during water and phosphate deficiency.
Eco-Friendly Estimation of Heavy Metal Contents in Grapevine Foliage Using In-Field Hyperspectral Data and Multivariate Analysis

Heavy metal monitoring in food-producing ecosystems can play an important role in human health safety. Since they are able to interfere with plants’ physiochemical characteristics, which influence the optical properties of leaves, they can be measured by in-field spectroscopy. In this study, the predictive power of spectroscopic data is examined. Five treatments of heavy metal stress (Cu, Zn, Pb, Cr, and Cd) were applied to grapevine seedlings and hyperspectral data (350–2500 nm), and heavy metal contents were collected based on in-field and laboratory experiments. The partial least squares (PLS) method was used as a feature selection technique, and multiple linear regressions (MLR) and support vector machine (SVM) regression methods were applied for modelling purposes. Based on the PLS results, the wavelengths in the vicinity of 2431, 809, 489, and 616 nm; 2032, 883, 665, 564, 688, and 437 nm; 1865, 728, 692, 683, and 356 nm; 863, 2044, 415, 652, 713, and 1036 nm; and 1373, 631, 744, and 438 nm were found most sensitive for the estimation of Cu, Zn, Pb, Cr, and Cd contents in the grapevine leaves, respectively. Therefore, visible and red-edge regions were found most suitable for estimating heavy metal contents in the present study. Heavy metals played a significant role in reforming the spectral pattern of stressed grapevine compared to healthy samples, meaning that in the best structures of the SVM regression models, the concentrations of Cu, Zn, Pb, Cr, and Cd were estimated with R2 rates of 0.56, 0.85, 0.71, 0.80, and 0.86 in the testing set, respectively. The results confirm the efficiency of in-field spectroscopy in estimating heavy metals content in grapevine foliage.
Serum Carnosinase-1 and Albuminuria Rather than the CNDP1 Genotype Correlate with Urinary Carnosinase-1 in Diabetic and Nondiabetic Patients with Chronic Kidney Disease

Background Carnosinase-1 (CN-1) can be detected in 24 h urine of healthy individuals and patients with type 2 diabetes (T2DM). We aimed to assess whether urinary CN-1 is also reliably measured in spot urine and investigated its association with renal function and the albumin/creatinine ratio (ACR). We also assessed associations between the CNDP1 (CTG)n genotype and CN-1 concentrations in serum and urine. Methods Patients with T2DM (n = 85) and nondiabetic patients with chronic kidney disease (CKD) (n = 26) stratified by albuminuria (ACR ≤ 300 mg/g or ACR > 300 mg/g) recruited from the nephrology clinic and healthy subjects (n = 24) were studied. Results Urinary CN-1 was more frequently detected and displayed higher concentrations in patients with ACR > 300 mg/g as compared to those with ACR ≤ 300 mg/g irrespective of the baseline disease (T2DM: 554 ng/ml [IQR 212-934 ng/ml] vs. 31 ng/ml [IQR 31-63 ng/ml] (p < 0.0001) and nondiabetic CKD: 197 ng/ml [IQR 112-739] vs. 31 ng/ml [IQR 31-226 ng/ml] (p = 0.015)). A positive correlation between urinary CN-1 and ACR was found (r = 0.68, p < 0.0001). Multivariate linear regression analysis revealed that ACR and serum CN-1 concentrations but not eGFR or the CNDP1 genotype are independent predictors of urinary CN-1, explaining 47% of variation of urinary CN-1 concentrations (R2 = 0.47, p < 0.0001). Conclusion These results confirm and extend previous findings on urinary CN-1 concentrations, suggesting that assessment of CN-1 in spot urine is as reliable as in 24 h urine and may indicate that urinary CN-1 in macroalbuminuric patients is primarily serum-derived and not locally produced.
Some convergent results for Backtracking Gradient Descent method on Banach spaces

Our main result concerns the following condition: {\bf Condition C. } Let $X$ be a Banach space. A $C^1$ function $f:X\rightarrow \mathbb{R}$ satisfies Condition C if whenever $\{x_n\}$ weakly converges to $x$ and $\lim _{n\rightarrow\infty}||\nabla f(x_n)||=0$, then $\nabla f(x)=0$. We assume that there is given a canonical isomorphism between $X$ and its dual $X^*$, for example when $X$ is a Hilbert space. {\bf Theorem. } Let $X$ be a reflexive, complete Banach space and $f:X\rightarrow \mathbb{R}$ be a $C^2$ function which satisfies Condition C. Moreover, we assume that for every bounded set $S\subset X$, then $\sup _{x\in S}||\nabla ^2f(x)||<\infty$. We choose a random point $x_0\in X$ and construct by the Local Backtracking GD procedure (which depends on $3$ hyper-parameters $\alpha ,\beta ,\delta _0$, see later for details) the sequence $x_{n+1}=x_n-\delta (x_n)\nabla f(x_n)$. Then we have: 1) Every cluster point of $\{x_n\}$, in the {\bf weak} topology, is a critical point of $f$. 2) Either $\lim _{n\rightarrow\infty}f(x_n)=-\infty$ or $\lim _{n\rightarrow\infty}||x_{n+1}-x_n||=0$. 3) Here we work with the weak topology. Let $\mathcal{C}$ be the set of critical points of $f$. Assume that $\mathcal{C}$ has a bounded component $A$. Let $\mathcal{B}$ be the set of cluster points of $\{x_n\}$. If $\mathcal{B}\cap A\not= \emptyset$, then $\mathcal{B}\subset A$ and $\mathcal{B}$ is connected. 4) Assume that $X$ is separable. Then for generic choices of $\alpha ,\beta ,\delta _0$ and the initial point $x_0$, if the sequence $\{x_n\}$ converges - in the {\bf weak} topology, then the limit point cannot be a saddle point.
Evaluation of UAV LiDAR for Mapping Coastal Environments

Unmanned Aerial Vehicle (UAV)-based remote sensing techniques have demonstrated great potential for monitoring rapid shoreline changes. With image-based approaches utilizing Structure from Motion (SfM), high-resolution Digital Surface Models (DSM), and orthophotos can be generated efficiently using UAV imagery. However, image-based mapping yields relatively poor results in low textured areas as compared to those from LiDAR. This study demonstrates the applicability of UAV LiDAR for mapping coastal environments. A custom-built UAV-based mobile mapping system is used to simultaneously collect LiDAR and imagery data. The quality of LiDAR, as well as image-based point clouds, are investigated and compared over different geomorphic environments in terms of their point density, relative and absolute accuracy, and area coverage. The results suggest that both UAV LiDAR and image-based techniques provide high-resolution and high-quality topographic data, and the point clouds generated by both techniques are compatible within a 5 to 10 cm range. UAV LiDAR has a clear advantage in terms of large and uniform ground coverage over different geomorphic environments, higher point density, and ability to penetrate through vegetation to capture points below the canopy. Furthermore, UAV LiDAR-based data acquisitions are assessed for their applicability in monitoring shoreline changes over two actively eroding sandy beaches along southern Lake Michigan, Dune Acres, and Beverly Shores, through repeated field surveys. The results indicate a considerable volume loss and ridge point retreat over an extended period of one year (May 2018 to May 2019) as well as a short storm-induced period of one month (November 2018 to December 2018). The foredune ridge recession ranges from 0 m to 9 m. The average volume loss at Dune Acres is 18.2 cubic meters per meter and 12.2 cubic meters per meter within the one-year period and storm-induced period, respectively, highlighting the importance of episodic events in coastline changes. The average volume loss at Beverly Shores is 2.8 cubic meters per meter and 2.6 cubic meters per meter within the survey period and storm-induced period, respectively.
Step-Change in Friction Under Electrovibration

Rendering tactile effects on a touch screen via electrovibration has many potential applications. However, our knowledge on tactile perception of change in friction and the underlying contact mechanics are both very limited. In this article, we investigate the tactile perception and the contact mechanics for a step change in friction under electrovibration during a relative sliding between a finger and the surface of a capacitive touch screen. First, we conduct magnitude estimation experiments to investigate the role of normal force and sliding velocity on the perceived tactile intensity for a step increase and decrease in friction, called rising friction (RF) and falling friction (FF). To investigate the contact mechanics involved in RF and FF, we then measure the frictional force, the apparent contact area, and the strains acting on the fingerpad during sliding at a constant velocity under three different normal loads using a custom-made experimental set-up. The results show that the participants perceived RF stronger than FF, and both the normal force and sliding velocity significantly influenced their perception. These results are supported by our mechanical measurements; the relative change in friction, the apparent contact area, and the strain in the sliding direction were all higher for RF than those for FF, especially for low normal forces. Taken together, our results suggest that different contact mechanics take place during RF and FF due to the viscoelastic behavior of fingerpad skin, and those differences influence our tactile perception of a step change in friction.
Live attenuated pertussis vaccine BPZE1 induces a broad antibody response in humans.

BACKGROUND The live attenuated BPZE1 vaccine candidate induces protection against B. pertussis and prevents nasal colonization in animal models. Here we report on the responses in humans receiving a single intranasal administration of BPZE1. METHODS We performed multiple assays to dissect the immune responses induced in humans (n=12) receiving BPZE1, with particular emphasis on the magnitude and characteristics of the antibody responses. Such responses were benchmarked to adolescents (n=12) receiving the complete vaccination program of the currently used acellular pertussis vaccine (aPV). Using immunoproteomics analysis, novel immunogenic B. pertussis antigens were identified. RESULTS All BPZE1 vaccinees showed robust B. pertussis-specific antibody responses with regard to significant increase in one or more of the parameters IgG, IgA and memory B cells to B. pertussis antigens. BPZE1-specific T cells showed a Th1 phenotype and the IgG exclusively consisted of IgG1 and IgG3. In contrast, all aPV vaccinees showed a Th2-biased response. Immunoproteomics profiling revealed that BPZE1 elicited broader and different antibody specificities to B. pertussis antigens as compared to the aPV that primarily induced antibodies to the vaccine antigens. Moreover, BPZE1 was superior at inducing opsonizing antibodies that stimulated reactive oxygen species (ROS) production in neutrophils and enhanced bactericidal function, which was in line with that antibodies against adenylate cyclase toxin were only elicited by BPZE1. CONCLUSIONS The breadth of the antibodies, the Th1-type cellular response and killing mechanisms elicited by BPZE1 may hold prospects of improving vaccine efficacy and protection against B. pertussis transmission. TRIAL REGISTRATION ClinicalTrials.gov NCT02453048, NCT00870350FUNDING. ILiAD Biotechnologies, Swedish Research Council (Vetenskapsrådet), Swedish Heart-lung Foundation.
Early Exposure to THC Alters M-Cell Development in Zebrafish Embryos

Cannabis is one of the most commonly used illicit recreational drugs that is often taken for medicinal purposes. The psychoactive ingredient in cannabis is Δ9-Tetrahydrocannabinol (Δ9-THC, hereafter referred to as THC), which is an agonist at the endocannabinoid receptors CB1R and CB2R. Here, we exposed zebrafish embryos to THC during the gastrulation phase to determine the long-term effects during development. We specifically focused on reticulospinal neurons known as the Mauthner cells (M-cell) that are involved in escape response movements. The M- cells are born during gastrulation, thus allowing us to examine neuronal morphology of neurons born during the time of exposure. After the exposure, embryos were allowed to develop normally and were examined at two days post-fertilization for M-cell morphology and escape responses. THC treated embryos exhibited subtle alterations in M-cell axon diameter and small changes in escape response dynamics to touch. Because escape responses were altered, we also examined muscle fiber development. The fluorescent labelling of red and white muscle fibers showed that while muscles were largely intact, the fibers were slightly disorganized with subtle but significant changes in the pattern of expression of nicotinic acetylcholine receptors. However, there were no overt changes in the expression of nicotinic receptor subunit mRNA ascertained by qPCR. Embryos were allowed to further develop until 5 dpf, when they were examined for overall levels of movement. Animals exposed to THC during gastrulation exhibited reduced activity compared with vehicle controls. Together, these findings indicate that zebrafish exposed to THC during the gastrula phase exhibit small changes in neuronal and muscle morphology that may impact behavior and locomotion.
Comparison of the accuracy of three diagnostic criteria and estimating the prevalence of metabolic syndrome: A latent class analysis

Background: Metabolic syndrome (MetS) is a growing public health problem with a worldwide distribution, and its prevalence is rapidly increasing worldwide. Hence, this study aimed to compare the prevalence of MetS based on the International Diabetes Federation (IDF), the National Cholesterol Education Program Expert Panel Adult Treatment Panel III (NCEP ATP III), and the American Association of Clinical Endocrinologists (AACE) diagnostic criteria. Materials and Methods: In this cross-sectional study, a total of 4737 people aged 45–69 years were enrolled in the 2nd phase of Shahroud Eye Cohort Study. We evaluated the prevalence of MetS with 95% confidence intervals by age and sex groups and according to MetS components. The accuracy (sensitivity and specificity) of these three methods was compared using latent class analysis. Finally, kappa statistic was used to determine the agreement between the diagnostic methods. Results: The prevalence of MetS varied from a minimum of 47.2% (as defined by the AACE) to a maximum of 60.0% (as defined by the IDF). The sensitivity of the three diagnostic methods of IDF, NCEP ATP III, and AACE was 98.9%, 94.4%, and 91.1%, respectively, and the specificity of these three methods was 94.6%, 97.0%, and 98.4%, respectively. Moreover, the highest agreement was found between the definition of the IDF and the NCEP ATP III. Conclusion: The IDF diagnostic method has a higher sensitivity for the diagnosis of MetS in Iranian middle-aged people. It is recommended to use this method for identifying more people at risk of MetS.
FGF14 Functions as a Tumor Suppressor through Inhibiting PI3K/AKT/mTOR Pathway in Colorectal Cancer

We identified that Fibroblast Growth Factor 14 (FGF14) was preferentially methylated in colorectal cancer (CRC). In this study, we aimed to investigate the epigenetic regulation, biological function and molecular mechanism of FGF14 in CRC. The expression of FGF14 in CRC cell lines, normal human colon epithelial cell line, CRC tissues and paired adjacent normal tissues was detected by PCR and Western blot. The biological function of FGF14 in CRC was interrogated by cell viability assay, colony formation, flow cytometry, cell invasion and migration assay, as well as in vivo study. We found FGF14 was downregulated or silenced in all (10/10) CRC cell lines, while it was expressed in normal colonic tissues and normal human colon epithelial cell line. The expression of FGF14 was lower in primary CRCs as compared to their adjacent normal tissues. Significant higher methylation of FGF14 was observed in CRCs than that in normal tissues based on the data from TCGA database. The loss of FGF14 gene expression was restored by treatment with DNA methyltransferase inhibitor 5-Aza. Re-expression of FGF14 in CRC cell lines inhibited cell viability and colony formation, and induced cell apoptosis. FGF14 induced mitochondrial apoptosis and inhibited PI3K/AKT/mTOR pathway. In xenograft mouse model, overexpression of FGF14 significantly reduced tumor growth (P<0.001). In conclusion, FGF14 is a novel tumor suppressor, which suppresses cell proliferation and induces cell apoptosis via mediating PI3K/AKT/mTOR pathway.