Spatiotemporally Discriminative Video-Language Pre-Training with Text Grounding

Most of existing video-language pre-training methods focus on instance-level alignment between video clips and captions via global contrastive learning but neglect rich fine-grained local information, which is of importance to downstream tasks requiring temporal localization and semantic reasoning. In this work, we propose a simple yet effective video-language pre-training framework, namely G-ViLM, to learn discriminative spatiotemporal features. Two novel designs involving spatiotemporal grounding and temporal grouping promote learning local region-noun alignment and temporal-aware features simultaneously. Specifically, spatiotemporal grounding aggregates semantically similar video tokens and aligns them with noun phrases extracted from the caption to promote local region-noun correspondences. Moreover, temporal grouping leverages cut-and-paste to manually create temporal scene changes and then learns distinguishable features from different scenes. Comprehensive evaluations demonstrate that G-ViLM performs favorably against existing approaches on four representative downstream tasks, covering text-video retrieval, video question answering, video action recognition and temporal action localization. G-ViLM performs competitively on all evaluated tasks and in particular achieves R@10 of 65.1 on zero-shot MSR-VTT retrieval, over 9% higher than the state-of-the-art method

ATACgraph: Profiling genome-wide chromatin accessibility from ATAC-seq

Assay for transposase-accessible chromatin using sequencing data (ATAC-seq) is an efficient and precise method for revealing chromatin accessibility across the genome. Most of the current ATAC-seq tools follow chromatin immunoprecipitation sequencing (ChIP-seq) strategies that do not consider ATAC-seq-specific properties. To incorporate specific ATAC-seq quality control and the underlying biology of chromatin accessibility, we developed a bioinformatics software named ATACgraph for analyzing and visualizing ATAC-seq data. ATACgraph profiles accessible chromatin regions and provides ATAC-seq-specific information including definitions of nucleosome-free regions (NFRs) and nucleosome-occupied regions. ATACgraph also allows identification of differentially accessible regions between two ATAC-seq datasets. ATACgraph incorporates the docker image with the Galaxy platform to provide an intuitive user experience via the graphical interface. Without tedious installation processes on a local machine or cloud, users can analyze data through activated websites using pre-designed workflows or customized pipelines composed of ATACgraph modules. Overall, ATACgraph is an effective tool designed for ATAC-seq for biologists with minimal bioinformatics knowledge to analyze chromatin accessibility. ATACgraph can be run on any ATAC-seq data with no limit to specific genomes. As validation, we demonstrated ATACgraph on human genome to showcase its functions for ATAC-seq interpretation. This software is publicly accessible and can be downloaded at https://github.com/RitataLU/ATACgraph

Estrogen Enhances the Expression of the Multidrug Transporter Gene ABCG2-Increasing Drug Resistance of Breast Cancer Cells through Estrogen Receptors.

BACKGROUND: Multidrug resistance is a major obstacle in the successful therapy of breast cancer. Studies have proved that this kind of drug resistance happens in both human cancers and cultured cancer cell lines. Understanding the molecular mechanisms of drug resistance is important for the reasonable design and use of new treatment strategies to effectively confront cancers. RESULTS: In our study, ATP-binding cassette sub-family G member 2 (ABCG2), adenosine triphosphate (ATP) synthase and cytochrome c oxidase subunit VIc (COX6C) were over-expressed more in the MCF-7/MX cell line than in the normal MCF7 cell line. Therefore, we believe that these three genes increase the tolerance of MCF7 to mitoxantrone (MX). The data showed that the high expression of COX6C made MCF-7/MX have more stable on mitochondrial membrane potential (MMP) and reactive oxygen species (ROS) expression than normal MCF7 cells under hypoxic conditions. The accumulation of MX was greater in the ATP-depleted treatment MCF7/MX cells than in normal MCF7/MX cells. Furthermore, E2 increased the tolerance of MCF7 cells to MX through inducing the expression of ABCG2. However, E2 could not increase the expression of ABCG2 after the inhibition of estrogen receptor α (ERα) in MCF7 cells. According to the above data, under the E2 treatment, MDA-MB231, which lacks ER, had a higher sensitivity to MX than MCF7 cells. CONCLUSIONS: E2 induced the expression of ABCG2 through ERα and the over-expressed ABCG2 made MCF7 more tolerant to MX. Moreover, the over-expressed ATP synthase and COX6c affected mitochondrial genes and function causing the over-expressed ABCG2 cells pumped out MX in a concentration gradient from the cell matrix. Finally lead to chemoresistance

Esophageal secondary peristalsis following acid infusion and chemical clearance correlate with mucosal integrity and acid sensitivity in GERD patients

BACKGROUND: Acid sensitivity can be altered in patients with gastroesophageal reflux disease (GERD). Secondary peristalsis helps clear gastro-esophageal refluxate and residual ingested food bolus. OBJECTIVES: The aim of this study was to investigate the associations among acid sensitivity, esophageal mucosal integrity, chemical clearance, and secondary peristalsis before and after esophageal acid infusion. DESIGN: This was an investigator-initiated, prospective, cross-sectional study. METHODS: Adult reflux patients underwent high resolution manometry and 24 h impedance-pH monitoring off acid suppression to identify GERD phenotypes, including non-erosive reflux disease (NERD), reflux hypersensitivity (RH), and functional heartburn (FH). Secondary peristalsis was assessed using five rapid 20 mL air injections into the esophagus before and after infusion of hydrochloric acid (0.1 N) into the mid-esophagus. Conventional acid infusion parameters recorded included lag time, intensity rating, and sensitivity score. Chemical clearance was evaluated using the post-reflux swallow-induced peristaltic wave (PSPW), and mucosal integrity was assessed by the mean nocturnal baseline impedance (MNBI) derived from impedance-pH monitoring. RESULTS: A total of 88 patients (age 21-64 years, 62.5% women) completed the study including 12 patients with NERD, 45 with RH, and 31 with FH. There was no significant difference in acid infusion parameters between patients with NERD, RH, and FH. Upon acid infusion, patients who exhibited successful secondary peristalsis had longer lag time, higher MNBI, and shorter bolus contact time than those without secondary peristalsis. Meanwhile, patients with intact PSPW demonstrated significantly higher intensity ratings in response to acid perfusion and higher MNBI than those with impaired PSPW. The lag time correlated positively with MNBI ( CONCLUSION: In conclusion, the protective effect of esophageal secondary peristalsis and chemical clearance on esophageal mucosal integrity was demonstrated. Concerning acid sensitivity, longer lag time in patients with intact secondary peristalsis may be attributed to better esophageal mucosal integrity, while stronger intensity ratings may have a greater tendency to induce PSPW and protect esophageal mucosal integrity

Application of artificial intelligence in measuring novel pH-impedance metrics for optimal diagnosis of GERD

Novel metrics extracted from pH-impedance monitoring can augment the diagnosis of gastroesophageal reflux disease (GERD). Artificial intelligence (AI) is being widely used to improve the diagnostic capabilities of various diseases. In this review, we update the current literature regarding applications of artificial intelligence in measuring novel pH-impedance metrics. AI demonstrates high performance in the measurement of impedance metrics, including numbers of reflux episodes and post-reflux swallow-induced peristaltic wave index and, furthermore, extracts baseline impedance from the entire pH-impedance study. AI is expected to play a reliable role in facilitating measuring novel impedance metrics in patients with GERD in the near future

Clonal dissemination of the multi-drug resistant Salmonella enterica serovar Braenderup, but not the serovar Bareilly, of prevalent serogroup C1 Salmonella from Taiwan

<p>Abstract</p> <p>Background</p> <p>Nontyphoidal <it>Salmonella </it>is the main cause of human salmonellosis. In order to study the prevalent serogroups and serovars of clinical isolates in Taiwan, 8931 <it>Salmonellae </it>isolates were collected from 19 medical centers and district hospitals throughout the country from 2004 to 2007. The pulsed-field eletrophoresis types (PFGE) and antibiotic resistance profiles of <it>Salmonella enterica </it>serovars Bareilly (<it>S</it>. Bareilly) and Braenderup (<it>S</it>. Braenderup) were compared, and multi-drug resistance (MDR) plasmids were characterized.</p> <p>Results</p> <p>Over 95% of human salmonellosis in Taiwan was caused by five <it>Salmonella </it>serogroups: B, C1, C2-C3, D1, and E1. <it>S</it>. Typhymurium, <it>S</it>. Enteritidis, <it>S</it>. Stanley and <it>S</it>. Newport were the four most prevalent serovars, accounting for about 64% of isolates. While only one or two major serovars from four of the most prevalent serogroups were represented, four predominant serovars were found in serogroup C1 <it>Salmonellae</it>. The prevalence was decreasing for <it>S</it>. Choleraeuis and <it>S</it>. Braenderup, and S. Virchow and increasing for <it>S</it>. Bareilly. <it>S</it>. Braenderup mainly caused gastroenteritis in children; in contrast, <it>S</it>. Bareiley infected children and elderly people. Both serovars differed by <it>Xba</it>I-PFGE patterns. Almost all <it>S</it>. Bareilly isolates were susceptible to antibiotics of interest, while all lacked plasmids and belonged to one clone. Two distinct major clones in <it>S</it>. Braenderup were cluster A, mainly including MDR isolates with large MDR plasmid from North Taiwan, and cluster B, mainly containing susceptible isolates without R plasmid from South Taiwan. In cluster A, there were two types of conjugative R plasmids with sizes ranging from 75 to 130 kb. Type 1 plasmids consisted of replicons F1A/F1B, <it>bla</it>_TEM, IS<it>26</it>, and a class 1 integron with the genes <it>dfrA12</it>-<it>orfF</it>-<it>aadA2-qacE</it>Δ1-<it>sulI</it>. Type 2 plasmids belonged to incompatibility group Inc<it>I</it>, contained <it>tnpA</it>-<it>bla</it>_CMY-2-<it>blc</it>-<it>sugE </it>genetic structures and lacked both IS<it>26 </it>and class 1 integrons. Although type 2 plasmids showed higher conjugation capability, type 1 plasmids were the predominant plasmid.</p> <p>Conclusions</p> <p>Serogroups B, C1, C2-C3, D1, and E1 of <it>Salmonella </it>caused over 95% of human salmonellosis. Two prevalent serovars within serogroup C1, <it>S</it>. Bareilly and cluster B of S. Braenderup, were clonal and drug-susceptible. However, cluster A of <it>S</it>. Braenderup was MDR and probably derived from susceptible isolates by acquiring one of two distinct conjugative R plasmids.</p

Safety and effectiveness of new embolization microspheres SCBRM for intermediate-stage hepatocellular carcinoma: A feasibility study

Transarterial chemoembolization (TACE) is, currently, the recommended treatment for hepatocellular carcinoma (HCC). However, long-term chemoembolization triggers the inflammatory response and may lead to postembolization syndrome (PES). Although several types of degradable microspheres have been developed to reduce drug toxicity and PES incidence, the clinical outcomes remain unsatisfactory. Previously, we have developed a new type of spherical, calibrated, biodegradable, radiopaque microspheres (SCBRM) and demonstrated their safety and efficacy in a pig model. Thus, the goal of this feasibility study was to determine the clinical safety and efficacy of the new SCBRM in intermediate-stage HCC patients. In this study, 12 intermediate-stage HCC patients underwent TACE using SCBRM with a calibrated size of 100–250 μm. The disease control rates at 1 month and 3 months after TACE-SCBRM treatment were 100% and 75.0%, respectively. The objective response rates at 1 month and 3 months after treatment were 66.7% and 58.3%, respectively. Very few adverse events were observed with one patient developing nausea. One day after the treatment, alanine aminotransferase, alanine aminotransferase, and total bilirubin levels were slightly elevated in the patients, but all returned to baseline on day 7. The median and mean overall survival times were 33 months (interquartile range, 12.8–42.0) and 29.2 ± 14.3 months, respectively. The 1-year and 2-year survival rates were 91.7% and 58.3%, respectively. In conclusion, TACE with the new SCBRM microspheres is clinically safe and effective, and it represents a promising approach in the management of intermediate-stage HCC

Switch activation of PI-PLC downstream signals in activated macrophages with wortmannin

AbstractPhosphatidylinositol (4,5)-bisphosphate (PtdIns(4,5)P2) has been known to serve as a substrate for phosphatidylinositol 3-kinase (PI3K) and phosphoinositide-specific phospholipase C (PI-PLC), which can produce PtdIns(3,4,5)P3 and inositol 1,4,5-trisphosphate (Ins(1,4,5)P3) and diacylglycerol (DAG), respectively. In this study, we elucidated the role of PI-PLC during the LPS-activated mouse macrophages RAW264.7 treated with PI3K inhibitor wortmannin. First, wortmannin treatment enhanced Ins(1,4,5)P3 production and iNOS expression in LPS-activated macrophages. Inhibition of PI3K by p85 siRNA also showed an enhancement of iNOS expression. On the other hand, overexpression of PI3K by ras-p110 expression plasmid significantly decreased iNOS expression in LPS-activated macrophages. In addition, overexpression of wild-type or dominant-negative Akt expression plasmid did not affect the iNOS expression in LPS-activated macrophages. Second, treatment of PI-PLC inhibitor U73122 reversed the enhancement of iNOS expression, the increase of phosphorylation level of ERK, JNK and p38, and the increase of AP-1-dependent gene expression in wortmannin-treated and LPS-activated macrophages. However, NF-κB activity determined by EMSA assay and reporter plasmid assay did not change during LPS-activated macrophages with or without wortmannin. We propose that the inhibition of PI3K by wortmannin in mouse macrophages enhances the PI-PLC downstream signals, and subsequently increases the LPS induction of iNOS expression independently of Akt pathway