Miracle-dz/UniFAR-FTUs huggingface dataset:
Programmed Cell Death 1 and Programmed Cell Death Ligands in Extranodal Natural Killer/T Cell Lymphoma: Expression Pattern and Potential Prognostic Relevance

The programmed cell death 1/programmed cell death ligands (PD-1/PD-Ls) axis is a potential immune escape mechanism of cancers. However, data on the PD-1/PD-Ls pathway in EBV-associated extranodal natural killer/T cell lymphoma (ENKTL) and its clinical implication are limited. Herein, we characterized PD-1/PD-L expression and its prognosis relevance in 49 ENKTL patients in Thailand. PD-L1 was expressed frequently on both lymphoma cells (61.2%) and stroma (77.5%), whereas PD-L2 expression was more common on lymphoma (63.2%) than stromal cells. PD-1 was positive in 20.5% of stroma, but undetectable on lymphoma cells. There was no association between baseline clinical characteristics and the expression PD-1/PD-Ls. The survival of patients with PD-Ls on tumor cells was poor. For PD-L1-positive versus negative cases, the 2-year event-free survival (EFS) was 42.2 versus 71.8% (p = 0.03) and 2-year overall survival (OS) was 45.4 versus 78.9% (p = 0.02), respectively. Comparing between patients with PD-L2-positive and PD-L2-negative lymphoma, the 2-year EFS was 37.1 versus 82.4% (p = 0.02) and 2-year OS was 45.2 versus 82.4% (p = 0.03), respectively. Neither PD-1 nor PD-Ls expression in the stroma predicted outcomes. In conclusion, PD-Ls were frequently expressed on ENKTL cells and associated with inferior outcomes. Therefore, PD-Ls are potential prognostic biomarkers and the roles of immune checkpoint blockade therapy in ENKTL deserve further investigation.
Trans-endocytosis elicited by nectins transfers cytoplasmic cargo, including infectious material, between cells

ABSTRACT Here, we show that cells expressing the adherens junction protein nectin-1 capture nectin-4-containing membranes from the surface of adjacent cells in a trans-endocytosis process. We find that internalized nectin-1–nectin-4 complexes follow the endocytic pathway. The nectin-1 cytoplasmic tail controls transfer: its deletion prevents trans-endocytosis, while its exchange with the nectin-4 tail reverses transfer direction. Nectin-1-expressing cells acquire dye-labeled cytoplasmic proteins synchronously with nectin-4, a process most active during cell adhesion. Some cytoplasmic cargo remains functional after transfer, as demonstrated with encapsidated genomes of measles virus (MeV). This virus uses nectin-4, but not nectin-1, as a receptor. Epithelial cells expressing nectin-4, but not those expressing another MeV receptor in its place, can transfer infection to nectin-1-expressing primary neurons. Thus, this newly discovered process can move cytoplasmic cargo, including infectious material, from epithelial cells to neurons. We name the process nectin-elicited cytoplasm transfer (NECT). NECT-related trans-endocytosis processes may be exploited by pathogens to extend tropism. This article has an associated First Person interview with the first author of the paper. Highlighted Article: Characterization of a newly discovered nectin trans-endocytosis processes that not only transfers cell surface proteins but also cytoplasmic proteins. It can also transfer measles virus ribonucleocapsids, extending tropism to neurons.
White Matter Hyperintensity Regression: Comparison of Brain Atrophy and Cognitive Profiles with Progression and Stable Groups

Subcortical white matter hyperintensities (WMHs) in the aging population frequently represent vascular injury that may lead to cognitive impairment. WMH progression is well described, but the factors underlying WMH regression remain poorly understood. A sample of 351 participants from the Alzheimer’s Disease Neuroimaging Initiative 2 (ADNI2) was explored who had WMH volumetric quantification, structural brain measures, and cognitive measures (memory and executive function) at baseline and after approximately 2 years. Selected participants were categorized into three groups based on WMH change over time, including those that demonstrated regression (n = 96; 25.5%), stability (n = 72; 19.1%), and progression (n = 209; 55.4%). There were no significant differences in age, education, sex, or cognitive status between groups. Analysis of variance demonstrated significant differences in atrophy between the progression and both regression (p = 0.004) and stable groups (p = 0.012). Memory assessments improved over time in the regression and stable groups but declined in the progression group (p = 0.003; p = 0.018). WMH regression is associated with decreased brain atrophy and improvement in memory performance over two years compared to those with WMH progression, in whom memory and brain atrophy worsened. These data suggest that WMHs are dynamic and associated with changes in atrophy and cognition.
Periodically Time-Varying Memory State-Feedback Controller Synthesis for Uncertain Discrete-Time Linear Systems:The H2 Case

This study is concerned with the synthesis of periodically time-varying memory state-feedback controllers (PTVMSFCs) for discrete-time linear systems. In our preceding studies, we have already established a solid theoretical basis for the LMI-based (robust) H∞-PTVMSFCs synthesis, and the goal of this paper is to extend those results to the H2 performance criterion. In the H2 case, the main difficulty stems from the fact that we have to ensure the existence of common auxiliary variables for multiple LMI conditions that are related to the Lyapunov inequality and inequalities for bounding traces that characterze the H2 norm. We can indeed overcome this difficulty and derive a necessary and sufficient LMI condition for the optimal H2-PTVMSFC synthesis. Based on this result, we also consider robust H2-PTVMSFC synthesis for polytopic-type uncertain LTI systems.
Fatty acid and retinol-binding protein: A novel antigen for immunodiagnosis of human strongyloidiasis

The tenacious human parasitic helminth Strongyloides stercoralis is a significant health problem worldwide. The current lack of a definitive diagnostic laboratory test to rule out this infection necessitates designing more specific diagnostic methods. Fatty acid and retinol-binding protein (FAR) plays a crucial role in the development and reproduction of nematodes. We generated a recombinant form of this protein and determined its applicability for immunodiagnosis of S. stercoralis. The L3 form of S. stercoralis was harvested and used for RNA extraction and cDNA synthesis. The coding sequence of S. stercoralis FAR (SsFAR) was cloned into pET28a(+) vector, expressed in E. coli BL21 and purified. ELISA and immunoblotting were employed to determine the specificity and sensitivity of rSsFAR using a set of defined sera. In addition, we analyzed the phylogenetic relationship of SsFAR with different FAR sequences from other nematodes. The cloned SsFAR had an open reading frame of 447 bp encoding 147 amino acids, with a deduced molecular mass of 19 kD. The SsFAR amino acid sequence was 93% identical to FAR of S. ratti. For differential immunodiagnosis of strongyloidiasis, rSsFAR exhibited 100% sensitivity and 97% specificity. However, cross-reactivity with FAR proteins of other parasites, namely Toxocara canis and Echinococcus granulosus, was noted. Our results provide a novel approach for immunodiagnosis of S. stercoralis infections using rSsFAR with reliable sensitivity and specificity.
Association of dietary patterns and risk of cardiovascular disease events in the MASHAD cohort study.

BACKGROUND Cardiovascular disease (CVD) is the principal cause of mortality and disability in Iranian adults. We aimed to evaluate the relationship between dietary patterns and CVD incidence in a large sample of adults in northeastern Iran. METHODS The present study comprised a prospective study of 5706 CVD-free men and women aged 35-65 years who participated in a cohort study. All of the participants were followed up for a 6-year period. Dietary patterns were derived from a 65-item validated food frequency questionnaire and the factor analysis method was used to determine dietary patterns. RESULTS We identified two major dietary patterns: (i) a Balanced dietary pattern (a high intake of green leafy vegetables, other vegetables, fruits, dairy products, red meats, poultry, seafoods, legumes and nuts, as well as a low intake of sugar) and (ii) a Western dietary pattern (a high intake of sugar, tea, egg, snacks, fast foods, potato, carbonated beverages, pickled foods, organs meat and butter) by factor analysis. The hazard ratio (HR) and 95% confidence intervals (CIs) of total CVD in the highest versus lowest tertiles of the Balanced pattern were 1.29 (95% CI = 0.67-2.47; P = 0.44). The HR and 95% CIs of CVD in the highest versus lowest tertiles of Western pattern were 2.21 (95% CI = 1.08-4.45; P = 0.03). CONCLUSIONS During the 6-year follow-up, we found that adherence to a Balanced dietary pattern was not significantly associated with CVD events. However, adherence to a Western dietary pattern was associated with a significantly increased risk of CVD events and its associated risk.
The lymphoid-associated interleukin 7 receptor (IL7R) regulates tissue-resident macrophage development

ABSTRACT The discovery of a fetal origin for tissue-resident macrophages (trMacs) has inspired an intense search for the mechanisms underlying their development. Here, we performed in vivo lineage tracing of cells with an expression history of IL7Rα, a marker exclusively associated with the lymphoid lineage in adult hematopoiesis. Surprisingly, we found that Il7r-Cre labeled fetal-derived, adult trMacs. Labeling was almost complete in some tissues and partial in others. The putative progenitors of trMacs, yolk sac (YS) erythromyeloid progenitors, did not express IL7R, and YS hematopoiesis was unperturbed in IL7R-deficient mice. In contrast, tracking of IL7Rα message levels, surface expression, and Il7r-Cre-mediated labeling across fetal development revealed dynamic regulation of Il7r mRNA expression and rapid upregulation of IL7Rα surface protein upon transition from monocyte to macrophage within fetal tissues. Fetal monocyte differentiation in vitro produced IL7R+ macrophages, supporting a direct progenitor-progeny relationship. Additionally, blockade of IL7R function during late gestation specifically impaired the establishment of fetal-derived trMacs in vivo. These data provide evidence for a distinct function of IL7Rα in fetal myelopoiesis and identify IL7R as a novel regulator of trMac development. Highlighted Article: A mouse Il7r-Cre lineage-tracing model, together with blockade of IL7R function and germline deletion of IL7R, provide evidence for the interleukin 7 receptor as a regulator of fetal macrophage development during late gestation.
Stromal fibroblasts induce metastatic tumor cell clusters via epithelial–mesenchymal plasticity

This study highlights the cellular and molecular mechanisms by which stromal fibroblasts enable human breast cancer cells to form tumor cell clusters and acquire highly invasive and metastatic traits. Emerging evidence supports the hypothesis that multicellular tumor clusters invade and seed metastasis. However, whether tumor-associated stroma induces epithelial–mesenchymal plasticity in tumor cell clusters, to promote invasion and metastasis, remains unknown. We demonstrate herein that carcinoma-associated fibroblasts (CAFs) frequently present in tumor stroma drive the formation of tumor cell clusters composed of two distinct cancer cell populations, one in a highly epithelial (E-cadherinhiZEB1lo/neg: Ehi) state and another in a hybrid epithelial/mesenchymal (E-cadherinloZEB1hi: E/M) state. The Ehi cells highly express oncogenic cell–cell adhesion molecules, such as carcinoembryonic antigen-related cell adhesion molecule 5 (CEACAM5) and CEACAM6 that associate with E-cadherin, resulting in increased tumor cell cluster formation and metastatic seeding. The E/M cells also retain associations with Ehi cells, which follow the E/M cells leading to collective invasion. CAF-produced stromal cell-derived factor 1 and transforming growth factor-β confer the Ehi and E/M states as well as invasive and metastatic traits via Src activation in apposed human breast tumor cells. Taken together, these findings indicate that invasive and metastatic tumor cell clusters are induced by CAFs via epithelial–mesenchymal plasticity.
Genome Sequencing of the Japanese Eel (Anguilla japonica) for Comparative Genomic Studies on tbx4 and a tbx4 Gene Cluster in Teleost Fishes

Limbs originated from paired fish fins are an important innovation in Gnathostomata. Many studies have focused on limb development-related genes, of which the T-box transcription factor 4 gene (tbx4) has been considered as one of the most essential factors in the regulation of the hindlimb development. We previously confirmed pelvic fin loss in tbx4-knockout zebrafish. Here, we report a high-quality genome assembly of the Japanese eel (Anguilla japonica), which is an economically important fish without pelvic fins. The assembled genome is 1.13 Gb in size, with a scaffold N50 of 1.03 Mb. In addition, we collected 24 tbx4 sequences from 22 teleost fishes to explore the correlation between tbx4 and pelvic fin evolution. However, we observed complete exon structures of tbx4 in several pelvic-fin-loss species such as Ocean sunfish (Mola mola) and ricefield eel (Monopterus albus). More interestingly, an inversion of a special tbx4 gene cluster (brip1-tbx4-tbx2b- bcas3) occurred twice independently, which coincides with the presence of fin spines. A nonsynonymous mutation (M82L) was identified in the nuclear localization sequence (NLS) of the Japanese eel tbx4. We also examined variation and loss of hindlimb enhancer B (HLEB), which may account for pelvic fin loss in Tetraodontidae and Diodontidae. In summary, we generated a genome assembly of the Japanese eel, which provides a valuable genomic resource to study the evolution of fish tbx4 and helps elucidate the mechanism of pelvic fin loss in teleost fishes. Our comparative genomic studies, revealed for the first time a potential correlation between the tbx4 gene cluster and the evolutionary development of toxic fin spines. Because fin spines in teleosts are usually venoms, this tbx4 gene cluster may facilitate the genetic engineering of toxin-related marine drugs.
Cyclic Cell-Penetrating Peptides As Efficient Intracellular Drug Delivery Tools.

Cyclic cell-penetrating peptides are relatively a newer class of peptides that have a huge potential for the intracellular delivery of therapeutic agents aimed at treating challenging ailments like multidrug resistance bacterial diseases, cancer, and HIV infection. Although, cell-penetrating peptides (CPPs) have been extensively explored as intracellular delivery vehicles, however, they have some inherent limitations like poor stability, endosomal entrapment, toxicity, and suboptimal cell penetration. Owing to their favorable properties that avoid these limitations, cyclic CPPs can provide a good alternative to linear CPPs. Several reviews have been published in the last decade that cover CPPs and cyclic peptides independently. To the best of our knowledge, this is one of the first reviews that covers cyclic CPPs comprehensively in the light of studies published so far. In this review, we have detailed examples of cyclic CPPs, their structures, cyclization strategies followed by a detailed account of their advantages over their linear counterparts. A hot area in cyclic CPPs is the exploration of cell penetration mechanisms; this review highlights this topic in detail. Finally, we will review the applications of cyclic CPPs, followed by conclusions and future prospects.
Colocation of Tpm3.1 and myosin IIa heads defines a discrete subdomain in stress fibres

ABSTRACT Co-polymers of tropomyosin and actin make up a major fraction of the actin cytoskeleton. Tropomyosin isoforms determine the function of an actin filament by selectively enhancing or inhibiting the association of other actin binding proteins, altering the stability of an actin filament and regulating myosin activity in an isoform-specific manner. Previous work has implicated specific roles for at least five different tropomyosin isoforms in stress fibres, as depletion of any of these five isoforms results in a loss of stress fibres. Despite this, most models of stress fibres continue to exclude tropomyosins. In this study, we investigate tropomyosin organisation in stress fibres by using super-resolution light microscopy and electron microscopy with genetically tagged, endogenous tropomyosin. We show that tropomyosin isoforms are organised in subdomains within the overall domain of stress fibres. The isoforms Tpm3.1 and 3.2 (hereafter Tpm3.1/3.2, encoded by TPM3) colocalise with non-muscle myosin IIa and IIb heads, and are in register, but do not overlap, with non-muscle myosin IIa and IIb tails. Furthermore, perturbation of Tpm3.1/3.2 results in decreased myosin IIa in stress fibres, which is consistent with a role for Tpm3.1 in maintaining myosin IIa localisation in stress fibres. Summary: Super-resolution and electron microscopy are used to show that tropomyosin Tpm3.1 is periodically distributed along stress fibres and linked to the organisation of myosin II motors.
Droplet microfluidics: from proof-of-concept to real-world utility?

Droplet microfluidics constitutes a diverse and practical tool set that enables chemical and biological experiments to be performed at high speed and with enhanced efficiency when compared to conventional instrumentation. Indeed, in recent years, droplet-based microfluidic tools have been used to excellent effect in a range of applications, including materials synthesis, single cell analysis, RNA sequencing, small molecule screening, in vitro diagnostics and tissue engineering. Our 2011 Chemical Communications Highlight Article [Chem. Commun. , 2011, 47, 1936-1942] reviewed some of the most important technological developments and applications of droplet microfluidics, and identified key challenges that needed to be addressed in the short term. In the current contribution, we consider the intervening eight years, and assess the contributions that droplet-based microfluidics has made to experimental science in its broadest sense.
Locate and Detect Persons in Crowded Scenes Aided by Objectiveness Measure

Locating persons in crowded scenes is very difficult due to multi-resolution and complex environment. The other difficulty in pedestrian detection domain is the real time requirement, because the camera installed on the crossing road is in high definition. In this paper, we presented a multi-task pedestrian detection framework boosted by Bing feature. We firstly trained upright full-body, multi-person, half-body and head models, then we compute the object-ness score and generate 1000 proposals by Bing feature, and at last we apply different model to different aspect ratio of the detection proposals. The experiment results on the PASCAL VOC 2007 show that our method outperforms all the other methods and achieved lower miss rate than the state-of-the-art. The computation time cost is just the half of state-of-the-art method.
ToF-SIMS 3D Analysis of Thin Films Deposited in High Aspect Ratio Structures via Atomic Layer Deposition and Chemical Vapor Deposition

For the analysis of thin films, with high aspect ratio (HAR) structures, time-of-flight secondary ion mass spectrometry (ToF-SIMS) overcomes several challenges in comparison to other frequently used techniques such as electron microscopy. The research presented herein focuses on two different kinds of HAR structures that represent different semiconductor technologies. In the first study, ToF-SIMS is used to illustrate cobalt seed layer corrosion by the copper electrolyte within the large through-silicon-vias (TSVs) before and after copper electroplating. However, due to the sample’s surface topography, ToF-SIMS analysis proved to be difficult due to the geometrical shadowing effects. Henceforth, in the second study, we introduce a new test platform to eliminate the difficulties with the HAR structures, and again, use ToF-SIMS for elemental analysis. We use data image slicing of 3D ToF-SIMS analysis combined with lateral HAR test chips (PillarHall™) to study the uniformity of silicon dopant concentration in atomic layer deposited (ALD) HfO2 thin films.
ARCHES: A Randomized, Phase III Study of Androgen Deprivation Therapy With Enzalutamide or Placebo in Men With Metastatic Hormone-Sensitive Prostate Cancer

PURPOSE Enzalutamide, a potent androgen-receptor inhibitor, has demonstrated significant benefits in metastatic and nonmetastatic castration-resistant prostate cancer. We evaluated the efficacy and safety of enzalutamide in metastatic hormone-sensitive prostate cancer (mHSPC). METHODS ARCHES (ClinicalTrials.gov identifier: NCT02677896) is a multinational, double-blind, phase III trial, wherein 1,150 men with mHSPC were randomly assigned 1:1 to enzalutamide (160 mg/day) or placebo, plus androgen deprivation therapy (ADT), stratified by disease volume and prior docetaxel chemotherapy. The primary end point was radiographic progression-free survival. RESULTS As of October 14, 2018, the risk of radiographic progression or death was significantly reduced with enzalutamide plus ADT versus placebo plus ADT (hazard ratio, 0.39; 95% CI, 0.30 to 0.50; P < .001; median not reached v 19.0 months). Similar significant improvements in radiographic progression-free survival were reported in prespecified subgroups on the basis of disease volume and prior docetaxel therapy. Enzalutamide plus ADT significantly reduced the risk of prostate-specific antigen progression, initiation of new antineoplastic therapy, first symptomatic skeletal event, castration resistance, and reduced risk of pain progression. More men achieved an undetectable prostate-specific antigen level and/or an objective response with enzalutamide plus ADT (P < .001). Patients in both treatment groups reported a high baseline level of quality of life, which was maintained over time. Grade 3 or greater adverse events were reported in 24.3% of patients who received enzalutamide plus ADT versus 25.6% of patients who received placebo plus ADT, with no unexpected adverse events. CONCLUSION Enzalutamide with ADT significantly reduced the risk of metastatic progression or death over time versus placebo plus ADT in men with mHSPC, including those with low-volume disease and/or prior docetaxel, with a safety analysis that seems consistent with the safety profile of enzalutamide in previous clinical trials in castration-resistant prostate cancer.
Wavelet-Based Spectral–Spatial Transforms for CFA-Sampled Raw Camera Image Compression

Spectral–spatial transforms (SSTs) change a raw camera image captured using a color filter array (CFA-sampled image) from an RGB color space composed of red, green, and blue components into a decorrelated color space, such as YDgCbCr or YDgCoCg color space composed of luma, difference green, and two chroma components. This paper describes three types of wavelet-based SST (WSST) obtained by reorganizing all of the existing SSTs covered in this paper. First, we introduce three types of macropixel SST (MSST) implemented within each $2 \times 2$ macropixel. Next, we focus on two-channel Haar wavelet transforms, which are simple wavelet transforms, and three-channel Haar-like wavelet transforms in each MSST and replace the Haar and Haar-like wavelet transforms with Cohen–Daubechies–Feauveau (CDF) 5/3 and 9/7 wavelet transforms, which are customized on the basis of the original pixel positions in 2D space. Although the test data set is not big, in lossless CFA-sampled image compression based on JPEG 2000, the WSSTs improve the bitrates by about 1.67%–3.17% compared with not using a transform, and the WSSTs that use 5/3 wavelet transforms improve the bitrates by about 0.31%–0.71% compared with the best existing SST. Moreover, in lossy CFA-sampled image compression based on JPEG 2000, the WSSTs show about 2.25–4.40 dB and 26.04%–49.35% in the Bjøntegaard metrics (BD-PSNRs and BD-rates) compared with not using a transform, and the WSSTs that use 9/7 wavelet transforms improve the metrics by about 0.13–0.40 dB and 2.27%–4.80% compared with the best existing SST.