Large expert-curated database for benchmarking document similarity detection in biomedical literature search

Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency-Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research.Peer reviewe

Improving hand hygiene compliance among healthcare workers: an intervention study in a Hospital in Guizhou Province, China

Objective: Hand hygiene (HH) is a critical component for controlling hospital-acquired infection (HAI). The present study was designed to develop an intervention approach to improve compliance with HH among healthcare workers in a hospital setting. Methods: The HH intervention study was conducted in Guizhou Provincial People's Hospital, Guiyang, China and organized by its Department of HAI Management. It was an observational, prospective, quasiexperimental (before-after intervention) study. The study was divided into two phases: the baseline phase and the intervention phase. The investigative team included clinical monitoring staff and infection control practitioners who received a series of instructions on HH compliance, monitoring skills, and measurement of the use of HH products. Results: Based on 27,852 observations in a 17-month period, the rate of compliance with HH improved from 37.78% at baseline to 75.90% after intervention. Significant improvement in compliance and an increase in consumption of HH products was observed after intervention. The per patient-day consumption of alcohol-based hand rub products and handwash agents increased by 4.75 mL and 4.55 mL, respectively. The consumption of paper towels increased 3.41 sheets per patient-day. During the same period, the prevalence rate of HAI decreased 0.83%. Conclusions: This study demonstrates that a significant improvement in compliance with HH can be achieved through a systemic, multidimensional intervention approach involving all categories of healthcare workers in a hospital setting, which may result in a decrease of the HAI rate. Keywords: Hand hygiene, Compliance, Hospital-acquired infectio

Utilization of adipocyte-derived lipids and enhanced intracellular trafficking of fatty acids contribute to breast cancer progression

Abstract Background To determine whether adipocyte-derived lipids could be transferred into breast cancer cells and investigate the underlying mechanisms of subsequent lipolysis and fatty acid trafficking in breast cancer cells. Methods A Transwell co-culture system was used in which human breast cancer cells were cultured in the absence or presence of differentiated murine 3 T3-L1 adipocytes. Migration/invasion and proliferation abilities were compared between breast cancer cells that were cultivated alone and those co-cultivated with mature adipocytes. The ability of lipolysis in breast cancer cells were measured, as well as the expression of the rate-limiting lipase ATGL and fatty acid transporter FABP5. ATGL and FABP5 were then ablated to investigate their impact on the aggressiveness of breast cancer cells that were surrounded by adipocytes. Further, immunohistochemistry was performed to detect differential expression of ATGL and FABP5 in breast cancer tissue sections. Results The migration and invasion abilities of cancer cells were significantly enhanced after co-culture with adipocytes, accompanied by elevated lipolysis and expression of ATGL and FABP5. Abrogation of ATGL and FABP5 sharply attenuated the malignancy of co-cultivated breast cancer cells. However, this phenomenon was not observed if a lipid emulsion was added to the culture medium to substitute for adipocytes. Furthermore, epithelial-mesenchymal transaction was induced in co-cultivated breast cancer cells. That may partially due to the stimulation of PPARβ/δ and MAPK, which was resulted from upregulation of FABP5. As evidenced by immunohistochemistry, ATGL and FABP5 also had higher expression levels at the invasive front of the breast tumor, in where the adipocytes abound, compared to the central area in tissue specimens. Conclusions Lipid originating from tumor-surrounding adipocytes could be transferred into breast cancer cells. Adipocyte-cancer cell crosstalk rather than lipids alone induced upregulation of lipases and fatty acid transport protein in cancer cells to utilize stored lipids for tumor progression. The increased expression of the key lipase ATGL and intracellular fatty acid trafficking protein FABP5 played crucial roles in this process via fueling or signaling

Intracellular presence of Helicobacter pylori antigen and genes within gastric and vaginal Candida.

BackgroundHelicobacter pylori infections are generally acquired during childhood and affect half of the global population, but its transmission route remains unclear. It is reported that H. pylori can be internalized into Candida, but more evidence is needed for the internalization of H. pylori in human gastrointestinal Candida and vaginal Candida.MethodsCandida was isolated from vaginal discharge and gastric mucosa biopsies. We PCR-amplified and sequenced H. pylori-specific genes from Candida genomic DNA. Using optical and immunofluorescence microscopy, we identified and observed bacteria-like bodies (BLBs) in Candida isolates and subcultures. Intracellular H. pylori antigen were detected by immunofluorescence using Fluorescein isothiocyanate (FITC)-labeled anti-H. pylori IgG antibodies. Urease activity in H. pylori internalized by Candida was detected by inoculating with urea-based Sabouraud dextrose agar, which changed the agar color from yellow to pink, indicating urease activity.ResultsA total of 59 vaginal Candida and two gastric Candida strains were isolated from vaginal discharge and gastric mucosa. Twenty-three isolates were positive for H. pylori 16S rDNA, 12 were positive for cagA and 21 were positive for ureA. The BLBs could be observed in Candida cells, which were positive for H. pylori 16S rDNA, and were viable determined by the LIVE/DEAD BacLight Bacterial Viability kit. Fluorescein isothiocyanate (FITC)-conjugated antibodies could be reacted specifically with H. pylori antigen inside Candida cells by immunofluorescence. Finally, H. pylori-positive Candida remained positive for H. pylori 16S rDNA even after ten subcultures. Urease activity of H. pylori internalized by Candida was positive.ConclusionIn the form of BLBs, H. pylori can internalize into gastric Candida and even vaginal Candida, which might have great significance in its transmission and pathogenicity

Programmable Microparticle Array for In Situ Modification and Multiple miRNA Detection

Simultaneous detection of multiple miRNAs of one disease can greatly reduce misdiagnosis and improve the detection rate, which is helpful for early cancer diagnosis. Here, a programmable microparticle-array-based acoustic microchip for in situ simultaneous multiple miRNAs detection is developed. On this microchip, the multiple probes-labeled microparticle array can be procedurally arranged in a microfluidic reaction chamber when four orthogonally piezoelectric transducers are applied. The probes-labeled microparticle array offers a platform for full molecular contact under dynamic ultrasonic streaming, and the array supplies a multipoint data correction to reduce the false positive of the detection results for more precisely visible fluorescence multiple target miRNAs sensing. We employed miRNA-21, miRNA-210, and miRNA-155 as specific biomarkers of pancreatic cancer and successfully finished the multiple miRNAs simultaneous detection in the microchip with a detection limit of 139.1, 179.9, and 111.4 pM, respectively. Such a device is programmable by adjusting the imputing frequency and voltage, and target biomarkers can be easily collected when the ultrasound force is released for further analysis, which shows great potential in multiple miRNAs enrichment and simultaneous detection for cancer clinical diagnosis

Programmable Microparticle Array for In Situ Modification and Multiple miRNA Detection

Simultaneous detection of multiple miRNAs of one disease can greatly reduce misdiagnosis and improve the detection rate, which is helpful for early cancer diagnosis. Here, a programmable microparticle-array-based acoustic microchip for in situ simultaneous multiple miRNAs detection is developed. On this microchip, the multiple probes-labeled microparticle array can be procedurally arranged in a microfluidic reaction chamber when four orthogonally piezoelectric transducers are applied. The probes-labeled microparticle array offers a platform for full molecular contact under dynamic ultrasonic streaming, and the array supplies a multipoint data correction to reduce the false positive of the detection results for more precisely visible fluorescence multiple target miRNAs sensing. We employed miRNA-21, miRNA-210, and miRNA-155 as specific biomarkers of pancreatic cancer and successfully finished the multiple miRNAs simultaneous detection in the microchip with a detection limit of 139.1, 179.9, and 111.4 pM, respectively. Such a device is programmable by adjusting the imputing frequency and voltage, and target biomarkers can be easily collected when the ultrasound force is released for further analysis, which shows great potential in multiple miRNAs enrichment and simultaneous detection for cancer clinical diagnosis

The new 6q27 tumor suppressor DACT2, frequently silenced by CpG methylation, sensitizes nasopharyngeal cancer cells to paclitaxel and 5-FU toxicity via β-catenin/Cdc25c signaling and G2/M arrest

Abstract Background Nasopharyngeal carcinoma (NPC) is prevalent in South China, including Hong Kong and Southeast Asia, constantly associated with Epstein-Barr virus (EBV) infection. Epigenetic etiology attributed to EBV plays a critical role in NPC pathogenesis. Through previous CpG methylome study, we identified Disheveled-associated binding antagonist of beta-catenin 2 (DACT2) as a methylated target in NPC. Although DACT2 was shown to regulate Wnt signaling in some carcinomas, its functions in NPC pathogenesis remain unclear. Methods RT-PCR, qPCR, MSP, and BGS were applied to measure expression levels and promoter methylation of DACT2 in NPC. Transwell, flow cytometric analysis, colony formation, and BrdU-ELISA assay were used to assess different biological functions affected by DACT2. Immunofluorescence, Western blot, and dual-luciferase reporter assay were used to explore the mechanisms of DACT2 functions. Chemosensitivity assay was used to measure the impact of DACT2 on chemotherapy drugs. Results We found that DACT2 is readily expressed in multiple normal adult tissues including upper respiratory tissues. However, it is frequently downregulated in NPC and correlated with promoter methylation. DNA methyltransferase inhibitor 5-aza-2′-deoxycytidine restored its expression in NPC cells. DACT2 methylation was further detected in 29/32 (91%) NPC tumors but not in any (0/8) normal nasopharyngeal tissue samples. Ectopic expression of DACT2 in NPC cells suppressed their proliferation, migration, and invasion through downregulating matrix metalloproteinases. DACT2 expression also induced G2/M arrest in NPC cells through directly suppressing β-catenin/Cdc25c signaling, which sensitized NPC cells to paclitaxel and 5-FU, but not cisplatin. Conclusion Our results demonstrate that DACT2 is frequently inactivated epigenetically by CpG methylation in NPC, while it inhibits NPC cell proliferation and metastasis via suppressing β-catenin/Cdc25c signaling. Our study suggests that DACT2 promoter methylation is a potential epigenetic biomarker for the detection and chemotherapy guidance of NPC

Risk of hematologic malignancies after breast ductal carcinoma in situ treatment with ionizing radiation

The increased incidence of secondary hematologic malignancies (SHM) is a well-known, potentially fatal, complication after cancer treatment. It is unknown if patients with ductal carcinoma in situ (DCIS) of the breast treated with external beam radiotherapy (RT) and who survive long-term have increased risks of secondary hematologic malignancies (SHM), especially for low/intermediate-risk subsets with limited benefits from RT. DCIS patients in Surveillance, Epidemiology, and End Results (SEER) registries (1975–2016) were identified. Relative risks (RR), hazard ratio (HR), and standardized incidence ratios (SIR) were calculated to assess the SHM risk and subsequent survival times. SHM development, defined as a nonsynchronous SHM occurring ≥1 year after DCIS diagnosis, was our primary endpoint. Of 184,363 eligible patients with DCIS, 77,927 (42.3%) in the RT group, and 106,436 (57.7%) in the non-RT group, 1289 developed SHMs a median of 6.4 years (interquartile range, 3.5 to 10.3 years) after their DCIS diagnosis. Compared with DCIS patients in the non-RT group, RT was associated with increased early risk of developing acute lymphoblastic leukemia (ALL; hazard ratio, 3.15; 95% CI, 1.21 to 8.17; P = 0.02), and a delayed risk of non-Hodgkin lymphoma (NHL; hazard ratio, 1.33; 95% CI, 1.09 to 1.62; P < 0.001). This increased risk of ALL and NHL after RT was also observed in subgroup analyses restricted to low/intermediate-risk DCIS. In summary, our data suggest that RT after breast conserving surgery for DCIS patients should be cautiously tailored, especially for low and intermediate-risk patients. Long-term SHM surveillance after DCIS diagnosis is warranted