Miracle-dz/UniFAR-FTUs huggingface dataset:
Introduction to the Thematic Minireview Series: Chromatin and transcription

Regulation of transcription in eukaryotic cells is a dynamic interplay between chromatin structure and recruitment of a plethora of transcription factors to enhancers, upstream activator sequences, and proximal promoter elements. These factors serve to recruit RNA polymerase to the core promoter for productive transcription. In this Thematic Minireview Series on chromatin and transcription, five reviews summarize current knowledge of diverse aspects of transcriptional regulation and the role of chromatin structure in transcription and development.
Improve3C: Data Cleaning on Consistency and Completeness with Currency

Data quality plays a key role in big data management today. With the explosive growth of data from a variety of sources, the quality of data is faced with multiple problems. Motivated by this, we study the multiple data quality improvement on completeness, consistency and currency in this paper. For the proposed problem, we introduce a 4-step framework, named Improve3C, for detection and quality improvement on incomplete and inconsistent data without timestamps. We compute and achieve a relative currency order among records derived from given currency constraints, according to which inconsistent and incomplete data can be repaired effectively considering the temporal impact. For both effectiveness and efficiency consideration, we carry out inconsistent repair ahead of incomplete repair. Currency-related consistency distance is defined to measure the similarity between dirty records and clean ones more accurately. In addition, currency orders are treated as an important feature in the training process of incompleteness repair. The solution algorithms are introduced in detail with examples. A thorough experiment on one real-life data and a synthetic one verifies that the proposed method can improve the performance of dirty data cleaning with multiple quality problems which are hard to be cleaned by the existing approaches effectively.
Links between fish abundance and ocean biogeochemistry as recorded in marine sediments

Fish populations are linked to ocean biogeochemistry by their reliance on primary production for food, and dissolved oxygen to breathe. It is also possible that marine fish modify biogeochemical dynamics, as do freshwater fish, through top-down trophic cascades, but there has been relatively little consideration of this possibility. This lack of consideration may reflect a lack of importance; alternatively, it may simply reflect the lack of appropriate observations with which to constrain such relationships. Here, we draw attention to the potential use of marine sediments as long-term simultaneous monitors of both fish abundance and marine biogeochemical dynamics. We compile published sediment proxy records of fish abundance from the west coasts of the Americas, and compare them with biogeochemical proxy measurements made at the same sites. Despite the challenges of using sediment records and the potential convolution of ecological and climatic signals, we find a small number of statistically significant relationships between fish debris and biogeochemical variables, at least some of which are likely to reflect causal relationships. Considering TOC, the most commonly-measured biogeochemical variable, some positive correlations with fish abundance are found, consistent with bottom-up control of fish abundance by primary production, or a planktivore-herbivore-phytoplankton trophic cascade. Negative correlations are also found, which could reflect sedimentary processes, the influence of upwelling-driven oxygen and nutrient dynamics on primary production and fish populations, and/or impacts of fish stocks on carbon fluxes by altering the recycling of carbon within the water column. Although the number of available measurements is too small to draw strong conclusions, the results point to plausible cases of bottom-up forcing, trophic cascades, and influence of dissolved oxygen concentrations on fish habitat.
miR-29b inhibits the progression of multiple myeloma through downregulating FOXP1

ABSTRACT Background: Increasing evidence has suggested that miR-29b plays an antitumor effect in multiple malignancies via the regulation of cell proliferation, apoptosis, invasion and migration. In the present study, we aimed to explore the underlying function and mechanism of miR-29b in multiple myeloma (MM). Methods: The expression of miR-29b in MM cell lines and tissues was detected by quantitative real-time PCR (qRT–PCR). CCK-8 and flow cytometry analyses were performed to assess cell proliferation, cycles and apoptosis. Bioinformatics, Dual-Luciferase reporter and qRT–PCR assays were employed to explore the possible correlation between miR-29b and FOXP1. Xenograft model was established to confirm the role of miR-29b on tumor growth in vivo. Results: miR-29b expression was markedly decreased in MM cell lines and tissues and downregulated miR-29b was closely related to International Staging System (ISS) stages. Exogenous overexpression of miR-29b inhibited the proliferation but induced MM cell cycle arrest and apoptosis. FOXP1 was identified as a direct target gene for miR-29b, and restoration of FOXP1 weakened miR-29b-induced anti-proliferation and pro-apoptosis in MM cell lines. Finally, the inhibitory effects of miR-29b on the growth of MM tumors were validated in mice. Conclusions: miR-29b recedes the progression of MM via downregulating FOXP1, which may provide a potential biological target for MM treatment.
Comparison of Intraocular Pressure Changes During the Water Drinking Test Between Different Fluid Volumes in Patients With Primary Open-angle Glaucoma

Purpose: The main objective of this study was to compare the intraocular pressure (IOP) response during the water drinking test (WDT) performed with 800 mL, 1000 mL, and 10 mL/kg of body weight and to test its relationship with body mass index (BMI). Methods: In this prospective, observer-masked, observational study, patients treated with primary open-angle glaucoma were evaluated. In group I, 29 consecutive patients with body weight ⩽60 kg underwent an 800 mL fluid challenge followed by a second WDT session with 10 mL/kg of body weight no longer than 4 months apart. Group II included 30 consecutive patients with body weight >60 kg who underwent a 1000 mL fluid challenge followed by an 800 mL test no longer than 4 months apart. IOP was measured before (baseline) and after water ingestion every 15 minutes for 45 minutes. Results: In group I, there was no significant difference in baseline or peak IOP between 800 mL and 10 mL/kg of body weight tests (P=0.12 and 0.56, respectively). However, 10 mL/kg tended to lead to consistently lower IOP values and a biased response in eyes with higher IOP. In group II, there was also no significant difference in baseline or peak IOP between 800 and 1000 mL tests (P=0.26 and 0.72, respectively). No biased response was observed in this group. There was no significant association between IOP peak and BMI with 800 mL (P=0.18), 10 mL/kg (P=0.29), or 1000 mL (P=0.34). Conclusions: There was overall good agreement between WDT results with different fluid volumes. The response to the volume loads tested in this study was not influenced by the BMI.
Discovery and development of differentially methylated regions in human papillomavirus‐related oropharyngeal squamous cell carcinoma

Human papillomavirus (HPV)‐related oropharyngeal squamous cell carcinoma (OPSCC) exhibits a different composition of epigenetic alterations. In this study, we identified differentially methylated regions (DMRs) with potential utility in screening for HPV‐positive OPSCC. Genome wide DNA methylation was measured using methyl‐CpG binding domain protein‐enriched genome sequencing (MBD‐seq) in 50 HPV‐positive OPSCC tissues and 25 normal tissues. Fifty‐one DMRs were defined with maximal methylation specificity to cancer samples. The Cancer Genome Atlas (TCGA) methylation array data was used to evaluate the performance of the proposed candidates. Supervised hierarchical clustering of 51 DMRs found that HPV‐positive OPSCC had significantly higher DNA methylation levels compared to normal samples, and non‐HPV‐related head and neck squamous cell carcinoma (HNSCC). The methylation levels of all top 20 DNA methylation biomarkers in HPV‐positive OPSCC were significantly higher than those in normal samples. Further confirmation using quantitative methylation specific PCR (QMSP) in an independent set of 24 HPV‐related OPSCCs and 22 controls showed that 16 of the 20 candidates had significant higher methylation levels in HPV‐positive OPSCC samples compared with controls. One candidate, OR6S1, had a sensitivity of 100%, while 17 candidates (KCNA3, EMBP1, CCDC181, DPP4, ITGA4, BEND4, ELMO1, SFMBT2, C1QL3, MIR129–2, NID2, HOXB4, ZNF439, ZNF93, VSTM2B, ZNF137P and ZNF773) had specificities of 100%. The prediction accuracy of the 20 candidates rang from 56.2% to 99.8% by receiver operating characteristic analysis. We have defined 20 highly specific DMRs in HPV‐related OPSCC, which can potentially be applied to molecular‐based detection tests and improve disease management.
Simulation of the Dynamics of Primary Immunodeficiencies in B Cells

Primary immunodeficiencies (PIDs) are a group of over 300 hereditary, heterogeneous, and mainly rare disorders that affect the immune system. Various aspects of immune system and PID proteins and genes have been investigated and facilitate systems biological studies of effects of PIDs on B cell physiology and response. We reconstructed a B cell network model based on data for the core B cell receptor activation and response processes and performed semi-quantitative dynamic simulations for normal and B cell PID failure modes. The results for several knockout simulations correspond to previously reported molecular studies and reveal novel mechanisms for PIDs. The simulations for CD21, CD40, LYN, MS4A1, ORAI1, PLCG2, PTPRC, and STIM1 indicated profound changes to major transcription factor signaling and to the network. Significant effects were observed also in the BCL10, BLNK, BTK, loss-of-function CARD11, IKKB, MALT1, and NEMO, simulations whereas only minor effects were detected for PIDs that are caused by constitutively active proteins (PI3K, gain-of-function CARD11, KRAS, and NFKBIA). This study revealed the underlying dynamics of PID diseases, confirms previous observations, and identifies novel candidates for PID diagnostics and therapy.
Innovative Distribution Priorities for the Medical Devices Industry in the Fourth Industrial Revolution

Purpose This study aimed to set priorities for improving the medical device distribution structure and to suggest an innovative improvement plan for the distribution structure using the analytic hierarchy process (AHP) method, focusing on stakeholders in the medical device industry. Methods This study conducted a survey with 35 specialists using the AHP method, which is a multiple-criteria decisionmaking methodology, in order to set priorities for improvement plans to address the problems faced by the medical device distribution structure. Results The AHP analysis showed that supply stability was the most important factor, followed by greater transparency, efficiency, smart supply, and cost reduction. Conclusions It is necessary to establish a stable supply system and manage crises through supply stability, as well as to provide opportunities for fair trade through greater transparency. As steps towards those goals, we propose establishing a unique device identification system, an information disclosure system, online distribution, and a group purchasing organization system in Korea.
Multimotion Visual Odometry (MVO): Simultaneous Estimation of Camera and Third-Party Motions

Estimating motion from images is a well-studied problem in computer vision and robotics. Previous work has developed techniques to estimate the motion of a moving camera in a largely static environment (e.g., visual odometry) and to segment or track motions in a dynamic scene using known camera motions (e.g., multiple object tracking). It is more challenging to estimate the unknown motion of the camera and the dynamic scene simultaneously. Most previous work requires a priori object models (e.g., tracking-by-detection), motion constraints (e.g., planar motion), or fails to estimate the full $SE\ (3)$ motions of the scene (e.g., scene flow). While these approaches work well in specific application domains, they are not generalizable to unconstrained motions. This paper extends the traditional visual odometry (VO) pipeline to estimate the full $SE\ (3)$ motion of both a stereo/RGB-D camera and the dynamic scene. This multimotion visual odometry (MVO) pipeline requires no a priori knowledge of the environment or the dynamic objects. Its performance is evaluated on a real-world dynamic dataset with ground truth for all motions from a motion capture system.
Role of Small Hydrophobic Protein of J Paramyxovirus in Virulence

Paramyxoviruses are associated with many devastating diseases in animals and humans. J paramyxovirus (JPV) was isolated from moribund mice in Australia in 1972. Newly isolated viruses, such as Beilong virus (BeiPV) and Tailam virus (TlmPV), have genome structures similar to that of JPV. A new paramyxovirus genus, Jeilongvirus, which contains JPV, BeiPV, and TlmPV, has been proposed. Small hydrophobic (SH) protein is present in many paramyxoviruses. Our present study investigates the role of SH protein of JPV in pathogenesis in its natural host. Understanding the pathogenic mechanism of Jeilongvirus is important to control and prevent potential diseases that may emerge from this group of viruses. ABSTRACT J paramyxovirus (JPV) was first isolated from moribund mice with hemorrhagic lung lesions in Australia in 1972. It is a paramyxovirus classified under the newly proposed genus Jeilongvirus. JPV has a genome of 18,954 nucleotides, consisting of eight genes in the order 3′-N-P/V/C-M-F-SH-TM-G-L-5′. JPV causes little cytopathic effect (CPE) in tissue culture cells but severe disease in mice. The small hydrophobic (SH) protein is an integral membrane protein encoded by many paramyxoviruses, such as mumps virus (MuV) and respiratory syncytial virus (RSV). However, the function of SH has not been defined in a suitable animal model. In this work, the functions of SH of JPV, MuV, and RSV have been examined by generating recombinant JPV lacking the SH protein (rJPV-ΔSH) or replacing SH of JPV with MuV SH (rJPV-MuVSH) or RSV SH (rJPV-RSVSH). rJPV-ΔSH, rJPV-MuVSH, and rJPV-RSVSH were viable and had no growth defect in tissue culture cells. However, more tumor necrosis factor alpha (TNF-α) was produced during rJPV-ΔSH infection, confirming the role of SH in inhibiting TNF-α production. rJPV-ΔSH induced more apoptosis in tissue culture cells than rJPV, rJPV-MuVSH, and rJPV-RSVSH, suggesting that SH plays a role in blocking apoptosis. Furthermore, rJPV-ΔSH was attenuated in mice compared to rJPV, rJPV-MuVSH, and rJPV-RSVSH, indicating that the SH protein plays an essential role in virulence. The results indicate that the functions of MuV SH and RSV SH are similar to that of JPV SH even though they have no sequence homology. IMPORTANCE Paramyxoviruses are associated with many devastating diseases in animals and humans. J paramyxovirus (JPV) was isolated from moribund mice in Australia in 1972. Newly isolated viruses, such as Beilong virus (BeiPV) and Tailam virus (TlmPV), have genome structures similar to that of JPV. A new paramyxovirus genus, Jeilongvirus, which contains JPV, BeiPV, and TlmPV, has been proposed. Small hydrophobic (SH) protein is present in many paramyxoviruses. Our present study investigates the role of SH protein of JPV in pathogenesis in its natural host. Understanding the pathogenic mechanism of Jeilongvirus is important to control and prevent potential diseases that may emerge from this group of viruses.
Bone mesenchymal stem cells transplantation combined with mild hypothermia improves the prognosis of cerebral ischemia in rats

Bone marrow mesenchymal stem cells (BMSCs) are used as a great promising choice for the treatment of cerebral ischemia. Herein, we discuss the neuroprotective effects of the combination of BMSCs transplantation and mild hypothermia (MH) in an ischemia-reperfusion rat model. First, BMSCs were isolated using density gradient centrifugation and the adherent screening method, followed by culture, identification and labeling with DAPI. Second, adult male SD rats were divided into 5 groups: sham group (surgery without blockage of middle cerebral artery), model group (middle cerebral artery occlusion (MCAO) was established 2h prior to reperfusion), BMSCs group (injection of BMSCs via the lateral ventricle 24h after MCAO), MH group (mild hypothermia for 3h immediately after MCAO) and combination therapy group (combination of BMSCs and MH). Finally, the modified neurological severity score (mNSS) test was performed to assess behavioral function at different time points (before MCAO, before transplantation, at day 1, day 5 and day 10 after transplantation). After that, the brain was subjected to TTC staining, and the homing and angiogenesis were evaluated by immumofluorescence and immunohistochemistry. Immunofluorescence staining and Western Blot analysis were performed to calculate the percentage of the infarct area and explore glial fibrillary acidic protein (GFAP) and vascular endothelial growth factor (VEGF). Our results showed that the combination therapy significantly decreased mNSS scores (P<0.01) and reduced the percentage of the infarct area (P<0.01) than a single treatment. Moreover, the expression of GFAP and VEGF increased significantly in the combination therapy group (at day 5, day 10 after transplantation; at all time points after transplantation, respectively) compared to the single treatment groups. Taken together, it was suggested that the combination of BMSCs transplantation and MH can significantly reduce the percentage of the infarct area and improve functional recovery by promoting homing and angiogenesis, which may be a beneficial treatment for cerebral ischemia.
Clinical and molecular predictors of long-term response in HER2 positive metastatic breast cancer patients

ABSTRACT Background: HER2+ metastatic breast cancer (MBC) is a poor prognosis disease, unusually curable. To date, no predictive factors have been clearly correlated with long-term response to anti-HER2 agents. Methods: 54 HER2+ MBC patients treated with HER2 targeted therapy as first line treatment were analysed: 40 with a time to progression longer than 3 years in Long Responders (LR) group and 14 with a progression disease within one year of anti-HER2 therapy in a control group named Early Progressors (EP). The expression of 770 genes and 13 molecular pathways were evaluated using Nanostring PanCancer pathway panel performed on FFPE BC tissues. Results: Considering baseline patients and tumor characteristics, EP women had more CNS spread and more metastatic burden of disease compared to LR (p > 0.05). Gene expression analysis identified 30 genes with significantly different expression in the two cohorts; five were driver genes (BRCA1, PDGFRA, AR, PHF6 and MSH2). The majority of these genes were over-expressed, mainly in LR patients, and encoded growth factors, pro- or anti-inflammatory interleukins and DNA repair factors. Only four genes were down regulated, all in EP group (TNFSF10, CACNG1, IL20RB and BRCA1). Most of these genes were involved in MAPK and PI3K pathways. MAPK pathway was differently expressed between LR and EP (p = 0.05). PI3K was the only pathway overexpressed in EP patients. Conclusions: Whole genome expression analysis comparing LR vs. EP identified a group of genes that may predict more favourable long-term outcomes. Up-regulation of MAPK and down-regulation of PI3K pathway could be a positive predictive factors. Further clinical implications are warranted. Abbreviations: BC: breast cancer; MBC: metastatic breast cancer; LR: long responder; EP: early progressor; FFPE: formalin-fixed paraffin-embedded; CNS: central nervous system; PFS: progression free survival; OS: overall survival.
CD30 Characterizes Polylobated Lymphocytes and Disease Progression in HTLV-1–Infected Individuals

Purpose: Although expression of CD30 is reported in a subset of adult T-cell leukemia/lymphoma cases, its clinicopathologic significance is poorly understood. We aimed to characterize CD30-positive cells and clarify their tumorigenic role in human T-cell lymphotropic virus type 1 (HTLV-1)–infected cells. Experimental Design: CD30-positive peripheral blood mononuclear cells from individuals with differing HTLV-1 disease status were characterized, and the role of CD30 signaling was examined using HTLV-1–infected cell lines and primary cells. Results: CD30-positive cells were detected in all samples examined, and the marker was coexpressed with both CD25 and CD4. This cell population expanded in accordance with disease progression. CD30-positive cells showed polylobation, with some possessing “flower cell” features, active cycling, and hyperploidy. CD30 stimulation of HTLV-1–infected cell lines induced these features and abnormal cell division, with polylobation found to be dependent on the activation of PI3K. The results thus link the expression of CD30, which serves as a marker for HTLV-1 disease status, to an active proliferating cell fraction featuring polylobation and chromosomal aberrations. In addition, brentuximab vedotin, an anti-CD30 monoclonal antibody conjugated with auristatin E, was found to reduce the CD30-positive cell fraction. Conclusions: Our results indicate that CD30-positive cells act as a reservoir for tumorigenic transformation and clonal expansion during HTLV-1 infection. The CD30-positive fraction may thus be a potential molecular target for those with differing HTLV-1 disease status. Clin Cancer Res; 24(21); 5445–57. ©2018 AACR.
Effects of human impacts on habitat use, activity patterns and ecological relationships among medium and small felids of the Atlantic Forest

Competition theory and niche theory suggest that two morphologically similar species may coexist by reducing the overlap of at least one dimension of their ecological niche. The medium and small Neotropical felids are an interesting group of carnivore species for studying intraguild competition. Due to differences in size it is expected that the larger ocelot exert strong interference competition on the smaller felids (southern tiger cat, margay and jaguarundi); which, in turn, may exert exploitative competition among themselves. Moreover, landscape changes due to human activities may alter these interspecific interactions. We studied the habitat use and the spatial and temporal interspecific relations of the medium and small Atlantic Forest felids, in a landscape with different levels of anthropogenic impact. We estimated the detection probability, and occupancy probability of these cats and whether these parameters are affected by environmental and anthropogenic variables or by the estimated occupancy and detection probability of the ocelot. We estimated the overlap in daily activity patterns between pairs of the four species and changes in their activity in response to anthropogenic impact. We also studied the potential changes that may have occurred in the daily activity of the small felids in relation to ocelot's occupancy probability. The probability of habitat use of the small- and medium-size felids was negatively associated to the intensity of landscape use by humans. Co-occurrence models indicated that the probability of habitat use by southern tiger cats decreased with ocelot occupancy probability. This effect was higher as human disturbance increased. Moreover, the ocelot and the southern tiger cat became more nocturnal in sites with higher human access, suggesting that they may be temporally avoiding encounters with humans or dogs. Conservation of medium and small felids in the Atlantic Forest depends not only on the establishment and implementations of protected areas but also on the management of human's land uses.