Miracle-dz/UniFAR-FTUs huggingface dataset:
TGF-β-Induced Endothelial to Mesenchymal Transition in Disease and Tissue Engineering

Endothelial to mesenchymal transition (EndMT) is a complex biological process that gives rise to cells with multipotent potential. EndMT is essential for the formation of the cardiovascular system during embryonic development. Emerging results link EndMT to the postnatal onset and progression of fibrotic diseases and cancer. Moreover, recent reports have emphasized the potential for EndMT in tissue engineering and regenerative applications by regulating the differentiation status of cells. Transforming growth factor β (TGF-β) engages in many important physiological processes and is a potent inducer of EndMT. In this review, we first summarize the mechanisms of the TGF-β signaling pathway as it relates to EndMT. Thereafter, we discuss the pivotal role of TGF-β-induced EndMT in the development of cardiovascular diseases, fibrosis, and cancer, as well as the potential application of TGF-β-induced EndMT in tissue engineering.
Gut Microbiota, Blood Metabolites, and Spleen Immunity in Broiler Chickens Fed Berry Pomaces and Phenolic-Enriched Extractives

This study evaluated the performance, gut microbiota, and blood metabolites in broiler chickens fed cranberry and blueberry products for 30 days. A total of 2,800 male day-old broiler Cobb-500 chicks were randomly distributed between 10 diets: control basal diet; basal diet with bacitracin (BACI); four basal diets with 1 and 2% of cranberry (CP1, CP2) and blueberry (BP1, BP2) pomaces; and four basal diets supplemented with ethanolic extracts of cranberry (COH150, COH300) or blueberry (BOH150, BOH300) pomaces. All groups were composed of seven replicates (40 birds per replicate). Cecal and cloacal samples were collected for bacterial counts and 16S rRNA gene sequencing. Blood samples and spleens were analyzed for blood metabolites and gene expressions, respectively. The supplementation of COH300 and BOH300 significantly increased the body weight (BW) during the starting and growing phases, respectively, while COH150 improved (P < 0.05) the overall cumulated feed efficiency (FE) compared to control. The lowest prevalence (P = 0.01) of necrotic enteritis was observed with CP1 and BP1 compared to BACI and control. Cranberry pomace significantly increased the quinic acid level in blood plasma compared to other treatments. At days 21 and 28 of age, the lowest (P < 0.05) levels of triglyceride and alanine aminotransferase were observed in cranberry pomace and blueberry product–fed birds, respectively suggesting that berry feeding influenced the lipid metabolism and serum enzyme levels. The highest relative abundance of Lactobacillaceae was found in ceca of birds fed CP2 (P < 0.05). In the cloaca, BOH300 significantly (P < 0.005) increased the abundances of Acidobacteria and Lactobacillaceae. Actinobacteria showed a significant (P < 0.05) negative correlation with feed intake (FI) and FE in COH300-treated birds, whereas Proteobacteria positively correlated with the BW but negatively correlated with FI and FE, during the growing phase. In the spleen, cranberry products did not induce the release of any pro-inflammatory cytokines but upregulated the expression of several genes (IL4, IL5, CSF2, and HMBS) involved in adaptive immune responses in broilers. This study demonstrated that feed supplementation with berry products could promote the intestinal health by modulating the dynamics of the gut microbiota while influencing the metabolism in broilers.
Development of an Improved Rotational Orthosis for Walking With Arm Swing and Active Ankle Control

Based on interlimb neural coupling, gait robotic systems should produce walking-like movement in both upper and lower limbs for effective walking restoration. Two orthoses were previously designed in our lab to provide passive walking with arm swing. However, an active system for walking with arm swing is desirable to serve as a testbed for investigation of interlimb neural coupling in response to voluntary input. Given the important function of the ankle joint during normal walking, this work aimed to develop an improved rotational orthosis for walking with arm swing, which is called ROWAS II, and especially to develop and evaluate the algorithms for active ankle control. After description of the mechanical structure and control schemes of the overall ROWAS II system, the closed-loop position control and adjustable admittance control algorithms were firstly deduced, then simulated in Matlab/Simulink and finally implemented in the ROWAS II system. Six able-bodied participants were recruited to use the ROWAS II system in passive mode, and then to estimate the active ankle mechanism. It was showed that the closed-loop position control algorithms enabled the ROWAS II system to track the target arm-leg walking movement patterns well in passive mode, with the tracking error of each joint <0.7°. The adjustable admittance control algorithms enabled the participants to voluntarily adjust the ankle movement by exerting various active force. Higher admittance gains enabled the participants to more easily adjust the movement trajectory of the ankle mechanism. The ROWAS II system is technically feasible to produce walking-like movement in the bilateral upper and lower limbs in passive mode, and the ankle mechanism has technical potential to provide various active ankle training during gait rehabilitation. This novel ROWAS II system can serve as a testbed for further investigation of interlimb neural coupling in response to voluntary ankle movement and is technically feasible to provide a new training paradigm of walking with arm swing and active ankle control.
Myeloid-Derived Suppressor Cell-Derived Arginase-1 Oppositely Modulates IL-17A and IL-17F Through the ESR/STAT3 Pathway During Colitis in Mice

Myeloid-derived suppressor cells (MDSC) play a crucial role in regulating the intestinal immune response during colitis. We previously revealed an essential role of MDSC in promoting TH17 cell polarization, which was found to be arginase-1 (Arg-1)-dependent; however, the underlying mechanism remains obscure. Here we report that percentage of MDSC decreased in ArgmyeKO mice during DSS-induced colitis. IL-17A levels reduced but IL-17F levels increased significantly in the colorectum of ArgmyeKO mice, leading to severe tissue damage and high risk of mortality rate. Activation of estrogen receptor (ESR) increased pSTAT3 level in MDSC and consequently led to elevated percentage of MDSC and more Arg-1 and inducible nitric oxide synthase expression in MDSC. Increased level of IL-17A and reduced level of IL-17F alleviated colitis in mice consequently. Together, these findings demonstrate a protective role of MDSC-derived Arg-1 during colitis after activates ESR/STAT3 signaling in MDSC. High level of Arg-1 favors accumulation of IL-17A, but reduced IL-17F expression in the colorectum of mice and ultimately leading to relief of colitis, indicating a potential clinical impact of MDSC-derived Arg-1 for controlling inflammatory bowel disease. Graphical Abstract Schematic diagrams for the mechanisms of MDSC-derived Arg-1 in the polarization of TH17 cells in DSS-induced colitis mouse model. Quercetin binds to ESR expressed by MDSC, activates STAT3 and promotes Arg-1 secretion in MDSC. High level of Arg-1 facilitates TH17 cell polarization and enhances IL-17A expression but inhibits IL-17F level in the colorectum during colitis.
Poster: Inaudible High-throughput Communication Through Acoustic Signals

In recent decades, countless efforts have been put into the research and development of short-range wireless communication, which offers a convenient way for numerous applications (e.g., mobile payments, mobile advertisement). Regarding the design of acoustic communication, throughput and inaudibility are the most vital aspects, which greatly affect available applications that can be supported and their user experience. Existing studies on acoustic communication either use audible frequency band (e.g., <20kHz) to achieve a relatively high throughput or realize inaudibility using near-ultrasonic frequency band (e.g., 18-20kHz) which however can only achieve limited throughput. Leveraging the non-linearity of microphones, voice commands can be demodulated from the ultrasound signals, and further recognized by the speech recognition systems. In this poster, we design an acoustic communication system, which achieves high-throughput and inaudibility at the same time, and the highest throughput we achieve is over 17x higher than the state-of-the-art acoustic communication systems.
Pagoda

Massively multithreaded GPUs achieve high throughput by running thousands of threads in parallel. To fully utilize the their hardware, contemporary workloads spawn work to the GPU in bulk by launching large tasks, where each task is a kernel that contains thousands of threads that occupy the entire GPU. GPUs face severe underutilization and their performance benefits vanish if the tasks are narrow, i.e., they contain less than 512 threads. Latency-sensitive applications in network, signal, and image processing that generate a large number of tasks with relatively small inputs are examples of such limited parallelism. This article presents Pagoda, a runtime system that virtualizes GPU resources, using an OS-like daemon kernel called MasterKernel. Tasks are spawned from the CPU onto Pagoda as they become available, and are scheduled by the MasterKernel at the warp granularity. This level of control enables the GPU to keep scheduling and executing tasks as long as free warps are found, dramatically reducing underutilization. Experimental results on real hardware demonstrate that Pagoda achieves a geometric mean speedup of 5.52X over PThreads running on a 20-core CPU, 1.76X over CUDA-HyperQ, and 1.44X over GeMTC, the state-of-the-art runtime GPU task scheduling system.
Evaluation of competing mortalities in oral squamous cell carcinoma patients treated with surgical and nonsurgical therapies

Oral squamous cell carcinoma (OSCC) is the sixth most common malignancy in the world. The incidence of oral carcinoma is more prevalent in males as they are twice more likely to develop oral carcinoma than women. 90% of people who develop oral carcinoma are those who use some sort of tobacco products. The etiology appears to be multifactorial and strongly related to lifestyle, mostly habits and diet. The five-year survival rate of oral carcinoma is about 50% which has not changed significantly in recent 50 years despite of advances in treatment modalities. The `distinct reoccurrences, secondary malignancies, advance age and comorbid cardiopulmonary diseases are factors that predisposes patient to competing causes of death. *Correspondence to: Ashwini Nareshchandra Walke, MDS, Oral Pathologist, Riyadh, Saudi Arabia, Tel: 091-9975771205; E-mail: ashwiniwalke2210@gmail.com
Semen Cryopreservation for Ex Situ Management of Genetic Diversity in Chicken: Creation of the French Avian Cryobank1

The need for semen preservation in domestic birds is a result of the reduction in genetic variability of domestic bird livestock and of the increasing risk of line extinction for health and safety reasons. Cryopreservation of embryos and primordial germ cells (PGC) is not routinely feasible in birds. The project therefore involved semen frozen in optimal safety and traceable conditions. Whole blood samples were also frozen to provide samples of analyses of genomes and health status. The feasibility of using ex situ conservation, i.e., collecting biological material to be stored outside the usual production area of the species (ex situ genetic stock), to preserve and manage rare breeds was tested with 4 subfertile populations: 3 rare experimental lines used for research into energy metabolism (R+), growth (Y33), and immunity (B4/B4), reared under known health status and the oldest endangered patrimonial French breed, the Gauloise dorée with an unknown health status. A general infrastructure was set up for the health screening and remediation of diseases, collection and storage of frozen cells and 2 sites were created for the storage of frozen samples. The screening and remediation of diseases of the Gauloise dorée, which was contaminated with various Salmonella and Mycoplasma strains, was achieved by successive treatment of parents, incubated eggs and young chicks with Baytril followed by Tiamulin. For each line, 474 to 994 semen straws have been frozen, thawed, and the semen evaluated. Insemination of frozen-thawed semen into females of the same genetic origin or of an egg-type commercial breed produced chicks in every case. For the most subfertile lines, insemination with egg-type females significantly increased the reproductive success. In conclusion, we report on the benefits of a semen and blood cryobanking complex for the management of endangered lines and strains of domestic birds. Current stocks made possible the restoration of more than 96% of the initial genome. This project also provided technical solutions to resolve some of the health problems frequently encountered for gene preservation in poultry.
An investigation of cellular radiosensitivity associated with immunodeficiency.

DNA Double Strand Breaks (DSBs) are induced by ionising radiation, but also arise during normal physiological processes such as V(D)J recombination during lymphocyte development. The induction of DSBs leads to the activation of proteins involved in DNA repair, but also initiates p53 dependent pathways that can result in cell cycle arrest and/or apoptosis. Defects in this damage response network may therefore result in immunodeficiency and cellular radiosensitivity. Skin biopsies obtained from undefined immunodeficient patients were used to generate primary fibroblast lines, and a group of these demonstrated cellular radiosensitivity using fibroblast survival assays. Whilst radiation-induced lymphocyte apoptosis was found to be an unreliable measure of intrinsic radiosensitivity, the examination of fibroblast division early after irradiation determined that radiosensitive fibroblasts undergo distinct cell fates after irradiation. Further characterisation revealed that all the identified radiosensitive lines were able to initiate p53-dependent gene transcription after irradiation. Analysis suggested that one undefined line (F96) might harbour a defect in DSB repair. Sequence examination of F96 candidate genes confirmed the presence of 2 novel mutations in the Artemis DNA repair gene that were expressed from separate alleles. Cloning of the Artemis gene also allowed the discovery of a new alternative exon and many novel splice variants. Concurrently, the F96 line was found to induce abnormally high levels of p53 activation after irradiation, which was associated with a more widespread induction of p53 target genes. This indicated that after DNA damage, defects in DSB repair might combine with other genetic factors that impair cellular survival to confer a radiosensitive immunodeficient phenotype.
An investigation into the existence of cyprinid herpesvirus-3 encoded microRNAs

An investigation into the existence of Cyprinid herpesvirus 3 encoded microRNAs Cyprinid herpesvirus 3 (CyHV-3), a member of the Alloherpesviridae family, is a cause of mass mortalities in carp (Cyprinus carpio carpio) and koi (Cyprinus carpio koi) worldwide. It is difficult to detect the low levels of viral genomic DNA present in latently infected (carrier) fish. Recent evidence shows that latent herpesviral gene transcription is often confined to non-protein-coding genes including microRNAs (miRNAs). This study set out to determine if CyHV-3 encoded its own miRNAs and to investigate their suitability as biomarkers for the diagnosis of latent CyHV-3 infections. Extensive bioinformatic analysis of the CyHV-3 genome suggested the presence of non-conserved precursor-miRNA (pre-miRNA) genes. High throughput deep RNA sequencing of size-selected small RNA fractions from in vitro CyHV-3 lytic infections resulted in the identification of potential miRNAs, associated isomiRs and miRNA–offset RNA (moRNAs), a new functional class of small RNAs related to miRNAs. DNA microarray analysis, northern blotting and stem-loop RT-qPCR were used to definitively identify some of these as novel viral miRNAs. In all, seven CyHV-3 pre-miRNAs were identified and three of these were conclusively detected in vivo by stem-loop RT-qPCR. Tentative CyHV-3 mRNA targets for some of these miRNAs were also identified, thus offering insights into the possible role of these novel viral genes during infection. Potential homologues of some of these CyHV-3 pre-miRNAs were identified in the two closely related viruses CyHV-1 and -2, indicating that other members of the Alloherpesviridae family may also encode miRNAs. This is the first report of miRNA and miRNA-offset-RNAs being produced by a member of the Alloherpesviridae family. Collectively, these findings may help further our understanding of the biology of these economically important viruses and they may also serve as biomarkers for the identification of latently infected fish.
Translesional Pressure Gradient Alters Relationship Between Blood Pressure and Recurrent Stroke in Intracranial Stenosis

Supplemental Digital Content is available in the text. Background and Purpose— There is debate over an optimal systolic blood pressure (SBP) in secondary stroke prevention of patients with symptomatic intracranial atherosclerotic stenosis (sICAS). We investigated whether translesional pressure gradient across sICAS would alter the relationship between SBP and risk of recurrent stroke in such patients. Methods— We recruited patients with sICAS (50%–99% stenosis) confirmed in computed tomography angiography. We simulated blood flow across sICAS with computed tomography angiography-based computational fluid dynamics models. Translesional pressure ratio (PR=Pressurepost-stenotic/Pressurepre-stenotic) was calculated in each case. Pressure ratio (PR) ≤ median was defined as low PR, indicating larger translesional pressure gradient across sICAS. All patients received optimal medical treatment. We investigated the interaction of translesional PR and mean SBP during follow-up (SBPFU) in determining the risk of the primary outcome, recurrent ischemic stroke in the same territory within 1 year. Results— Among 157 patients with sICAS, the median PR was 0.93. Multivariate Cox regression revealed significant PR-SBPFU interaction on the primary outcome (P=0.008): in patients with normal PR, risk of primary outcome significantly decreased with lower SBPFU (hazard ratio for 10 mm Hg decrement =0.46; P=0.018); however, in those with low PR, SBPFU≤130 mm Hg was associated with significantly increased risk of primary outcome, compared with 130<SBPFU<150 mm Hg (hazard ratio=5.08; P=0.043). Conclusions— Low SBP level may be associated with increased risk of stroke recurrence in patients with sICAS with a large translesional pressure gradient. Translesional PR by computational fluid dynamics models may yield a promising indicator to guide more individualized blood pressure management in patients with sICAS, warranting future studies.
Recurrence of pigmented villonodular synovitis of the knee

Abstract Rationale: Pigmented villonodular synovitis is a rare disease which may involve any joints. It has localized and diffuse forms, and the latter is more aggressive with a higher recurrence rate. Different treatments are applied to each form of the disease, but there is no standard surgical procedure or any consensus on whether adjuvant therapy should be used. Many factors may lead to recurrence of the disease; however, there is no reliable way to predict the recurrence. Patient concerns: A 21-year-old female patient presented with a one-year history of progressive pain of the right knee. Diagnoses: Pigmented villonodular synovitis. Interventions: We performed an anterior approach arthroscopic synovectomy and a posterior approach open synovectomy in the popliteal fossa, but the patient declined to take radiotherapy as a post-surgical adjuvant therapy. Then, she received a repeat arthroscopic synovectomy 20 months later because of the recurrent lesions, and a radiotherapy was performed 6 weeks after the second surgery. Outcomes: There were no abnormal signs in the right knee on magnetic resonance imaging scanning 6 months after the second surgery. The range of motion of her right knee was normal. Lessons: Pigmented villonodular synovitis is a rare disease which may involve any joints. Surgical resection plus adjuvant therapy is recommended for patients with risk factors of recurrence.
Novel Mechanisms of Resistance to HIV-1 Reverse Transcriptase (RT) Inhibitors: A Molecular and Clinical Characterization of Mutations in the Connection and RNase H Domains of RT

Current antiretroviral therapy (ART) has reduced morbidity and mortality from HIV-1 infection, but the long-term efficacy of ART is limited by selection of HIV-1 drug-resistant variants. Most HIV-1 drug resistance mutations that have been studied are located in the polymerase domain of HIV-1 reverse transcriptase (RT) and this region of RT is sequenced in genotyping tests used clinically to guide ART. Recently, attention has focused on the connection and RNase H domains of RT as locations of drug resistance mutations, but the prevalence, molecular mechanisms, and impact of such mutations on response to ART are uncertain. We therefore performed a series of studies to address this uncertainty, including in vitro selection of HIV-1 resistant to 3'-azidothymidine (AZT), drug susceptibility studies, biochemical assays and genotype analysis of clinical samples to identify and characterize resistance mutations in the RT connection and RNase H domains. From this work, we provide several lines of evidence that connection and RNase H domain mutations emerge with ART and impact nucleoside/nucleotide reverse transcriptase inhibitor (NRTI) susceptibility. First, the connection domain mutation A371V and the RNase H domain mutation Q509L are selected in vitro with AZT and confer > 50-fold AZT resistance and low-level cross resistance to lamivudine, abacavir and tenofovir when in the context of thymidine analog mutations (TAMs) in the polymerase domain of RT. Second, we show that mutation Q509L in the RNase H domain promotes dissociation of RT from RNA/DNA template/primer bound in an RNase H competent mode, thereby decreasing secondary RNase H cleavage and destruction of the template/primer. As a consequence, template/primer binds in a polymerase competent mode allowing AZT-monophosphate excision, DNA polymerization and AZT resistance. Third, the connection domain mutation A360V emerges in patients after prolonged exposure to AZT monotherapy and increases resistance to AZT in the context of 3 or more TAMs. Fourth, connection and RNase H domain mutations are not more frequent at virologic failure in HIV-1 subtype B infected patients treated with 2 NRTI plus efavirenz when failure is defined as a small increase in plasma HIV-1 RNA. However, the connection domain mutation N348I emerges frequently at virologic failure in HIV-1 subtype C infected patients in South Africa who were treated with efavirenz/lamivudine/stavudine or nevirapine/lamivudine/stavudine when virologic failure is defined as confirmed plasma HIV-1 RNA > 1,000 copies/mL. This work provides strong evidence that RT connection and RNase H domain mutations emerge in HIV-1 infected patients treated with ART and these mutations are missed with currently available genotype tests. Mutations missed by routine genotyping tests pose a potential public health threat if left undetected and transmitted to others.