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Chirality has an important impact on chemical and biological research, as most active substances are chiral. In recent decades, metal–organic frameworks (MOFs), which are assembled from metal ions or clusters and organic linkers via metal–ligand bonding, have attracted considerable scientific interest due to their high crystallinity, exceptional porosity and tunable pore sizes, high modularity, and diverse functionalities. Since the discovery of the first functional chiral metal–organic frameworks (CMOFs), CMOFs have been involved in a variety of disciplines such as chemistry, physics, optics, medicine, and pharmacology. The introduction of defect engineering theory into CMOFs allows the construction of a class of defective CMOFs with high hydrothermal stability and multi-stage pore structure. The introduction of defects not only increases the active sites but also enlarges the pore sizes of the materials, which improves chiral recognition, separation, and catalytic reactions, and has been widely investigated in various fields. This review describes the design and synthesis of various defective CMOFs, their characterization, and applications. Finally, the development of the materials is summarized, and an outlook is given. This review should provide researchers with an insight into the design and study of complex defective CMOFs. [ABSTRACT FROM AUTHOR]

Based on ISO 17034 and ISO Guide 35, a new series of matrix reference materials for 23 trace elements in 2 mg/mL gold solutions with five concentration levels (0, 1, 5, 10 and 20) ng/mL were developed, respectively. High-purity gold CRM GBW02793 with purity of 99.9995 % used as raw material was dissolved and then doped with multi-element solutions to prepare the candidate RMs. For ICP-MS measurements, matrix-matched and internal standard calibrations were studied and evaluated. The limits of detection (LoDs) ranged from 0.002 to 0.35 ng/mL. The satisfactory spike recoveries from 96 % to 108 % were obtained, demonstrating the measurement trueness. The ICP-MS method was also applied in the homogeneity and stability study. The statistical analysis suggested that the elements were well distributed by measuring 11 units with duplicate analysis for each. Besides, no significant trends were observed in the long-term stability test at room temperature for 12 months or in the short-term stability test at 60 ℃ and − 20 ℃ for 7 days. Through collaborative characterization by eight expert laboratories, the RM at each concentration level was certified for the mass fractions of 23 elements, respectively. All applied measurement methods in the characterization were further validated by using CRM ERM-EB507. The measurement results from all laboratories showed great consistency, and the overall mean values which were consistent with the target values were used as the certified values. Additionally, uncertainties arising from inhomogeneity (ubb), instability (us) and value assignment (uchar) were comprehensively combined. The developed RMs would ensure reliable and traceable analytical results of trace elements in fine gold and gold jewelry. [ABSTRACT FROM AUTHOR]

Serine proteases (SP), including furin, trypsin, and TMPRSS2 cleave the SARS-CoV-2 spike (S) protein, enabling the virus to enter cells. Here, we show that factor (F) Xa, an SP involved in blood coagulation, is upregulated in COVID-19 patients. In contrast to other SPs, FXa exerts antiviral activity. Mechanistically, FXa cleaves S protein, preventing its binding to ACE2, and thus blocking viral entry and infection. However, FXa is less effective against variants carrying the D614G mutation common in all pandemic variants. The anticoagulant rivaroxaban, a direct FXa inhibitor, inhibits FXa-mediated S protein cleavage and facilitates viral entry, whereas the indirect FXa inhibitor fondaparinux does not. In the lethal SARS-CoV-2 K18-hACE2 model, FXa prolongs survival yet its combination with rivaroxaban but not fondaparinux abrogates that protection. These results identify both a previously unknown function for FXa and an associated antiviral host defense mechanism against SARS-CoV-2 and suggest caution in considering direct FXa inhibitors for preventing or treating thrombotic complications in COVID-19 patients. The serine protease factor Xa (FXa) is upregulated in COVID-19 patients and functions in the coagulation pathway. Here, Dong et al characterise the basis of its antiviral activity in the context of SARS-CoV-2 pandemic variants. [ABSTRACT FROM AUTHOR]

The support for the membrane is the basis for the preparation and application of the zeolite membrane. Moreover, its cost and properties directly determine the performance of the zeolite membrane and its industrial applications. A novel porous silicon carbide (SiC) support for zeolite membrane bonded with needle-like mullite (3Al2O3·2SiO2) was prepared using SiC powders as the raw material and kaolin, Al(OH)3, and AlF3 as the needle-like mullite precursor additives via an in situ high-temperature reactions in an air atmosphere. Effects of the support material composition and the sintering temperature on the sintering behavior, pore structure, permeability, and microstructure of the resultant supports were extensively investigated. The needle-like mullite formation consumed silicon oxide (SiO2) and generated a rigid skeleton structure with a good pore structure and bonding phase. Hence, the porous SiC support exhibited high porosity, with relatively large pore size and mechanical strength, which helped improve the support performance. Notably, the porous SiC support sintered at 1480 °C with in situ inter-particle needle-like mullite bonding exhibited excellent filtration and permeability performance. The porous support materials and methods used in this work are suitable for designing and preparing a novel porous SiC support for zeolite membranes. [ABSTRACT FROM AUTHOR]

Guidelines have shifted to now recommend endoscopic eradication therapy for Barrett's esophagus (BE) with low and high-grade dysplasia. Previously, esophagectomy was the standard therapy for high-grade dysplasia. However, it is unclear to what degree ablation therapy has affected utilization of esophagectomy. In this retrospective observational cohort study of BE patients without cancer from the Premier Healthcare Database, the prevalence of utilization of endoscopic ablation therapy and of esophagectomy in BE were calculated and temporal trends were evaluated. A total of 938, 333 BE cases were included in the study. There was a significantly increasing trend of ablation over the period 2006 to 2010 (Annual Percentage Change (APC); 95% CI 0.56% [0.51%, 0.61%]), a significantly decreasing trend for the period 2011 to 2015 (APC; 95% CI − 0.15% [− 0.20%, − 0.11%]), and a shallow increasing trend for the period 2016 to 2019 (APC; 95% CI 0.09% [0.06%, 0.11%]). For esophagectomy, there was a significantly decreasing trend for the period 2006 to 2009 (APC; 95% CI − 0.03% [− 0.04%, − 0.02%]; P < 0.001) that corresponded to the uptrend in utilization of endoscopic ablation. There was a stable trend of esophagectomy over the period 2010 to 2019 (APC; 95% CI − 0.0006% [− 0.0002%, 0.0005%]; P = 0.1947). Adoption and increased utilization of endoscopic ablation therapy for BE has coincided with a decrease in esophagectomy, and is the predominate method of therapy for BE with dysplasia. [ABSTRACT FROM AUTHOR]

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Neural progenitor cells (NPCs) transplantation is known as a potential strategy for treating spinal cord injury (SCI). This study aimed to investigate effects of insulin growth factor-1 (IGF-I) on NPCs proliferation and clarify associated mechanisms. NPCs isolated from T8-T10 segmental spinal cord tissues of rats were cultured and identification. Then, lentivirus packing plasmids containing IGF-I was constructed and used for NPCs infection. Cell proliferation was evaluated by detecting 5-Bromodeoxyuridine (BrdU) expression in NPCs, cell differentiation was detected using double-labeling immunofluorescence staining while cell apoptosis was detected using TUNEL assay. In addition, the signal expression of Akt/mTOR/p70S6K in NPCs cells were investigated using immunofluorescence staining and western blot assay. The experimental group was defined as pCMV-IGF-I group, while the negative control group was defined as pCMV-LacZ group. Cells infected with pCMV-IGF-I lentivirus followed by addition of 100 mg/ml rapamycin were defined as pCMV-IGF-I + Rapa group. NPCs were successfully isolated, identified and cultured. IGF-I overexpression significantly inhibited cell apoptosis and enhanced cell migration. Akt/mTOR/ p70S6K signaling cascade was proved to be present in NPCs, IGF-I overexpression significantly activated Akt/mTOR/p70S6K signaling cascade, while rapamycin addition inhibited its expression. Also, the activated Akt/mTOR/p70S6K signal cascade induced by IGF-I significantly enhanced BrdU expression and inhibited cell apoptosis, and promoted the differentiation of NPC into the neuronal system. However, the rapamycin addition inhibited the cell response induced by IGF-I overexpression. IGF-I overexpression could enhance cell proliferation, inhibit cell apoptosis and promote their differentiation into neuronal systems by activating Akt/mTOR/p70S6K signaling cascade in vitro, indicating that the Akt/mTOR/p70S6K signaling cascade may be the potentially mechanism for the endogenous repair and remodeling of spinal cord after injury. [ABSTRACT FROM AUTHOR]

Needle experience large variations in photosynthetic rates in response to cone presence and needle aging. Exploring the interaction effect of these factors on photosynthetic traits is helpful to understand the source-sink relationship between needles and cones. Here, we examined the impact of needle age on needle CO2 assimilation rate (Pn), needle mass per area (LMA), and needle concentration of soluble sugars, starch, total non-structural carbohydrates ([NSC]), nitrogen ([N]) and phosphorus ([P]) in cone‐bearing branches (reproductive branches) and branches without cones (vegetative branches) of Pinus koraiensis. We also compared instantaneous photosynthetic N-use efficiency (PNUE) and P-use efficiency (PPUE) in reproductive and vegetative branches. Our results showed that needles in reproductive branches had lower Pn, [N], [P], PNUE and PPUE than the needles in vegetative branches, but higher [NSC] and LMA. The differences between branch types were similar across needle ages, despite a clear effect of aging on photosynthetic traits: Pn, [N], [P], PNUE and PPUE decreased with increasing needle age, whereas LMA increased and [NSC] did not change with needle age. Unexpectedly, these results suggest that Pn in needles of reproductive branches is limited by NSC accumulation, and that N and P needed for cone development come from adjacent needles/reproductive branches while NSC come from more distant organs. These results shed light on the source-sink transport of carbon, N and P between needles and cones and are helpful for eventually predicting and improving crop size in Pinus koraiensis. [ABSTRACT FROM AUTHOR]

Engineered natural killer (NK) cells represent a promising option for immune therapy option due to their immediate availability in allogeneic settings. Severe acute diseases, such as COVID-19, require targeted and immediate intervention. Here we show engineering of NK cells to express (1) soluble interleukin-15 (sIL15) for enhancing their survival and (2) a chimeric antigen receptor (CAR) consisting of an extracellular domain of ACE2, targeting the spike protein of SARS-CoV-2. These CAR NK cells (mACE2-CAR_sIL15 NK cells) bind to VSV-SARS-CoV-2 chimeric viral particles as well as the recombinant SARS-CoV-2 spike protein subunit S1 leading to enhanced NK cell production of TNF-α and IFN-γ and increased in vitro and in vivo cytotoxicity against cells expressing the spike protein. Administration of mACE2-CAR_sIL15 NK cells maintains body weight, reduces viral load, and prolongs survival of transgenic mice expressing human ACE2 upon infection with live SARS-CoV-2. These experiments, and the capacity of mACE2-CAR_sIL15 NK cells to retain their activity following cryopreservation, demonstrate their potential as an allogeneic off-the-shelf therapy for COVID-19 patients who are faced with limited treatment options. Severe COVID-19 requires immediate and targeted intervention that is efficient against SARS-CoV-2 and its variants. Authors show here the therapeutic potential of engineered natural killer cells that simultaneously express a chimeric antigen receptor targeting the spike protein of SARS-CoV-2, and IL-15, a cytokine that enhances the function and survival of their own. [ABSTRACT FROM AUTHOR]

Stroke thrombolysis treatment is generally administered within 4.5 h, but a greater time window may be permitted depending upon the ischemic penumbra on neuroimaging. This observational cohort study investigated the outcomes of thrombolysis given within 12 h after symptom onset of lenticulostriate artery stroke. The population comprised 160 patients. Thrombolysis was administered via tissue plasminogen activator, alteplase (TPA). Thrombolysis was indicated by a mismatch between diffusion-weighted imaging (DWI) and T2-weighted imaging (T2WI), that is, an acute ischemic lesion on DWI without a corresponding lesion on T2WI. Demographics and medical history were compared with the modified Rankin scale (mRS) score, to reflect outcome. Patients with a favorable clinical outcome (mRS 0–1) had significantly lower hypertension, baseline NIH Stroke Scale (NIHSS) score, and admission systolic/diastolic blood pressure compared with patients with mRS 2–6. Lower admission systolic blood pressure and NIHSS score were significantly associated with favorable outcome. In patients either with IV-TPA within 4.5 h, or between 4.5 and 12 h, lower admission systolic blood pressure and/or NIHSS score similarly independently predict favorable outcome. However, in all groups, the onset-to-treatment time did not significantly influence the outcomes. We conclude that in our cohort higher admission systolic blood pressure and higher baseline NIHSS and not time were associated with poor outcome in patients with magnetic resonance-guided thrombolysis within 12 h of isolated lenticulostriate artery stroke, therefore loosening the traditionally perceived dependency of outcome on time. [ABSTRACT FROM AUTHOR]

The performance of zeolite membrane supports directly determines the synthesis performance and industrial application of zeolite membranes. In this study, a novel and high permeation SiC supports for NaA zeolite membrane were prepared by carrying out in situ reaction bonding at high temperature in the air atmosphere to coat the SiC particles with aluminum sol. The effects of process parameters on the formation of porous structure of SiC supports were systematically investigated, and the underlying mechanism was explored. During the sintering process, high-temperature Al2O3 from aluminum sol reacted with SiO2 generated by oxidation of the surface of SiC particles to form mullite, which exhibited excellent chemical stability and improved the mechanical properties and chemical stability of the supports. The porous SiC supports for zeolite membrane displayed obvious three-dimensional connected pore structure, with smooth inner surface of the pores and obvious connection neck between the particles. The porous SiC supports for zeolite membrane showed good in situ mullite bonding between the particles, and high permeability. It has a porosity of 36.3%, an average pore size of 1.42 µm and a bending strength of 32.4 MPa. All these figures indicate good comprehensive properties that are consistent with the rigorous requirements of zeolite membrane synthesis and industrial application. [ABSTRACT FROM AUTHOR]

In the multipass bundle-drawing process of multifilament composite wire of NbTi alloy, the cored wire is prone to damage and even fracture due to severe plastic deformation. Therefore, it is necessary to study the fracture mechanism of NbTi alloy in plastic deformation and conduct a model of the fracture process. A quasi-static uniaxial tensile test was conducted at room temperature, taking the Nb-47 wt.% Ti alloy as the experimental material. The fracture morphology and damage evolution were observed using scanning electron microscopy. The fracture morphology of the NbTi alloy presents a 'cup-cone' shape. The damage evolution shows the characteristics of microvoid nucleation and growth to microcrack formation, indicating that the fracture mechanism of the alloy is a typical microvoid coalescing ductile fracture. The Gurson–Tvergaard–Needleman (GTN) damage model is used in the finite element simulation for the uniaxial tensile process of NbTi alloy, and the microvoid volume fraction-related damage parameters in the model are determined by the reverse calibration method. The damage behavior in the multipass bundle-drawing process of the NbTi/Cu multifilament composite wire is predicted by the GTN damage model with calibrated damage parameters. [ABSTRACT FROM AUTHOR]

Paralytic shellfish toxins (PSTs) produced by certain marine dinoflagellates accumulate in filter-feeding marine bivalves. We used LC-MS/MS to detect and quantify 13 PSTs in 188 shellfish samples of 14 species collected from Shenzhen city's Buji seafood wholesale market from March 2019 to February 2020. Twenty-six of 188 shellfish samples (13.8%) were PSTs detectable. Within 14 species, 10 out of 34 noble clam Chlamys nobilis samples contain detectable PSTs with the highest detection rate 29.4%. Seven out of 17 samples from Nan'ao island contained detectable PSTs with the highest detection rate 41.2% among 11 origins. Samples containing PSTs were concentrated in spring and winter, with the highest levels in March>December>January. Among PSTs detected, C1 was dominant. Acute dietary exposure assessment for Shenzhen residents were based on mean adult body weight, 99th percentile daily shellfish consumption of Shenzhen food consumption survey 2008 and maximum PSTs concentration for each shellfish species. The outcome for Chlamys nobilis was 2.4~3.7-fold higher than recommended ARfDs. Mean PSTs concentration, P99, and mean shellfish consumption were used to assess chronic dietary exposure. The results were lower than recommended ARfDs. In conclusion, residents in Shenzhen are at risk for acute PSTs poisoning, while relatively safe from chronic PSTs exposure. [ABSTRACT FROM AUTHOR]

Oncolytic herpes simplex virus-1 is capable of lysing tumor cells while alerting the immune system. CD47, in collaboration with SIRPα, represents an important immune checkpoint to inhibit phagocytosis by innate immune cells. Here we show locoregional control of glioblastoma by an oncolytic herpes virus expressing a full-length anti(α)-human CD47 IgG1 or IgG4 antibody. The antibodies secreted by the virus-infected glioblastoma cells block the CD47 'don't eat me' signal irrespective of the subclass; however, αCD47-IgG1 has a stronger tumor killing effect than αCD47-IgG4 due to additional antibody-dependent cellular phagocytosis by macrophages and antibody-dependent cellular cytotoxicity by NK cells. Intracranially injected αCD47-IgG1-producing virus continuously releases the respective antibody in the tumor microenvironment but not into systemic circulation; additionally, αCD47-IgG1-producing virus also improves the survival of tumor-bearing mice better than control oncolytic herpes virus combined with topical αCD47-IgG1. Results from immunocompetent mouse tumor models further confirm that macrophages, and to a lesser extent NK cells, mediate the anti-tumor cytotoxicity of antibody-producing oncolytic herpesviruses. Collectively, oncolytic herpes simplex virus-1 encoding full-length antibodies could improve immune-virotherapy for glioblastoma. Oncolytic herpes simplex virus-1 lyses cancer cells while increases their immunogenicity. Blocking the CD47 "don't eat me" signal on cancer cells promotes their phagocytosis by macrophages. Authors here show that oncolytic viruses expressing anti-CD47 antibodies improve glioblastoma survival in mouse models. [ABSTRACT FROM AUTHOR]

The membrane support is the basis for the preparation and application of the zeolite membrane and its cost and properties directly determine the performance of the zeolite membrane as well as its industrial applications. In this paper, the direct synthesis of NaA zeolite membrane on a novel low-cost support via an in situ reaction by utilizing natural clay can enable a significant reduction in manufacturing costs. During the preparation of the support for the NaA zeolite membrane, additives, such as Al2O3, Al(OH)3 and AlF3, were combined with kaolin clay and used as alumina precursors. Using the resulting porous mullite support, the effects of the firing temperature on the permeability and pore structure of the support were investigated extensively. The results of the experiment showed that silica in the natural clay was reacted by the Al2O3 precursor additives, producing a needle-like mullite in situ that served as a rigid skeleton porous structure for the support. Thus, a network porous structure of the mullite support could be formed during sintering process. The prepared network porous structure mullite supports exhibited a high pure water permeance of 3324 L m2 h1 bar1, open porosity of 41.8% and a mean pore size of 1.36 µm which was ideal for the preparation of the NaA zeolite membrane. [ABSTRACT FROM AUTHOR]

Cancer cells are disordered by nature and thus featured by higher internal redox level than healthy cells. Redox imbalance could trigger programmed cell death if exceeded a certain threshold, rendering therapeutic strategies relying on redox control a possible cancer management solution. Yet, various programmed cell death events have been consecutively discovered, complicating our understandings on their associations with redox imbalance and clinical implications especially therapeutic design. Thus, it is imperative to understand differences and similarities among programmed cell death events regarding their associations with redox imbalance for improved control over these events in malignant cells as well as appropriate design on therapeutic approaches relying on redox control. This review addresses these issues and concludes by bringing affront cold atmospheric plasma as an emerging redox controller with translational potential in clinics. [ABSTRACT FROM AUTHOR]

Background: Previous studies have demonstrated that gene polymorphism is associated with cancer susceptibility. Most of these genes are involved in neoplastic processes. Previous studies demonstrated that tumor-suppressor candidate 7 (TUSC7) was a tumor-suppressor gene in various tumors. This study aims to explore the association between lncRNA TUSC7 polymorphism and gastric cancer susceptibility and the potential function. Methods: The tagging SNPs of TUSC7 were genotyped with polymerase chain reaction–restriction fragment length polymorphism (PCR–RFLP) in a Chinese Han population-based case–control study. The relative expression level of TUSC7 in plasma was conducted by quantitative real-time PCR (qRT-PCR). The gene–environment interaction was analyzed by multifactor dimensionality reduction (MDR). The dual luciferase reporter assay was used to examine whether SNP rs12494960 of TUSC7 allele variation affected the binding of lncRNA-TUSC7 and miRNAs miR-133a-3p. Results: Three tagging SNPs (rs12494960, rs1518338, rs2867837) of TUSC7 were selected to validate in population. The unconditional multiple logistic regression showed that individuals with genotype AA (OR: 1.79, 95% CI: 1.16, 2.70) of rs12494960 and GG (OR: 2.24, 95% CI: 1.12, 4.46) of rs2867837 in TUSC7 had increased risk of GC susceptibility. The qRT-PCR showed that CA and AA genotype of rs12494960 in TUSC7 had significantly lower relative expression level in plasma, compared with CC genotype. The dual luciferase reporter assay showed that TUSC7 and miR-133a-3p had interaction. Conclusion: The mutant genotype of rs12494960 could increase the susceptibility of gastric cancer and might affect the corresponding mRNA expression of lncRNA TUSC7 in plasma. [ABSTRACT FROM AUTHOR]

This study aimed to characterize porcine Achilles tendon (PAT) in terms of its structural components, vascularity, and resident tendon cells. We found that PAT is composed of a paratenon sheath, a core of fascicles, and an endotenon/interfascicular matrix (IFM) that encases the fascicle bundles. We analyzed each of these three tendon components structurally using tissue sections and by isolating cells from each component and analyzing in vitro. Many blood vessel-like tissues were present in the paratenon and IFM but not in fascicles, and the vessels in the paratenon and IFM appeared to be inter-connected. Cells isolated from the paratenon and IFM displayed characteristics of vascular stem/progenitor cells expressing the markers CD105, CD31, with α-smooth muscle actin (α-SMA) localized surrounding blood vessels. The isolated cells from paratenon and IFM also harbored abundant stem/progenitor cells as evidenced by their ability to form colonies and express stem cell markers including CD73 and CD146. Furthermore, we demonstrate that both paratenon and IFM-isolated cells were capable of undergoing multi-differentiation. In addition, both paratenon and IFM cells expressed elastin, osteocalcin, tubulin polymerization promoting protein (TPPP), and collagen IV, whereas fascicle cells expressed none of these markers, except collagen I. The neurotransmitter substance P (SP) was also found in the paratenon and IFM-localized surrounding blood vessels. The findings of this study will help us to better understand the vascular and cellular mechanisms of tendon homeostasis, injury, healing, and regeneration. [ABSTRACT FROM AUTHOR]

Background: The long noncoding RNA (lncRNA) nuclear-enriched abundant transcript 1 (NEAT1) has been implicated in many tumors risk including gastric cancer. However, the association of single nucleotide polymorphisms (SNPs) at NEAT1 with gastric cancer risk has not been studied. The aim of this study was to investigate the association between SNPs in NEAT1 and gastric cancer susceptibility. Methods: In this study, four SNPs in lncRNA NEAT1 were selected for genotyping in 484 gastric cancer patients and 484 controls in Chinese Han population. Quantitative real-time PCR (qRT-PCR) was conducted to evaluate the potential function of rs3825071. Attributable risk percentage (ARP) and population attributable risk percentage (PARP) were used to assess the epidemiological effect. Results: In the dominant model (GG), the genotypes AG + AA of rs3825071 and rs7943779 were associated with an increased risk of gastric cancer (OR = 1.72, 95%CI = 1.27–2.32 and OR = 1.63, 95%CI = 1.19–2.22). Individuals harboring ≥ 3 risk alleles have higher risk of gastric cancer (OR = 1.88, 95% CI = 1.26–2.80, P = 0.002). ARP and PARP associated with gastric cancer were 42.53% and 10.88% for rs3825071, and were 33.78% and 6.26% for rs7943779, respectively. Furthermore, compared with the genotype GG of rs3825071, the genotypes AG and AA had higher expression of NEAT1. Conclusions: We found that the genetic variations in NEAT1 were significantly associated with risk of gastric cancer. The G > A variant of rs3825071 may confer gastric cancer susceptibility by changed biological effects to increase the expression of NEAT1. [ABSTRACT FROM AUTHOR]

Background: Breast carcinomas are heterogeneous diseases with distinct clinical outcomes and cancer stem cell (CSC) percentages. Exploring breast carcinoma stem cell landscape could help understand the heterogeneity of such cancers with profound clinical relevance. Methods: We conducted transcriptional profiling of CSCs and non-stem cancer cells isolated from three triple-negative breast carcinoma cell lines, analyzed the CSC transcriptome landscape that drives breast carcinoma heterogeneity through differentially expressed gene identification, gene ontology (GO) and pathway enrichment analyses as well as network construction, and experimentally validated the network hub gene. Results: We identified a CSC feature panel consisting of 122 and 381 over-represented and under-expressed genes capable of differentiating breast carcinoma subtypes. We also underpinned the prominent roles of the PI3K-AKT pathway in empowering carcinoma cells with uncontrolled proliferative and migrative abilities that ultimately foster cancer stemness, and revealed the potential promotive roles of ATP6V1B1 on breast carcinoma stemness through functional in vitro studies. Conclusions: Our study contributes in identifying a CSC feature panel for breast carcinomas that drives breast carcinoma heterogeneity at the transcriptional level, which provides a reservoir for diagnostic marker and/or therapeutic target identification once experimentally validated as demonstrated by ATP6V1B1. [ABSTRACT FROM AUTHOR]

Osteosarcoma (OS) is the most common malignant bone tumor in children and young adults. Despite that high-risk factors have been identified, no test for early detection is available. This study aimed to identify circulating nucleic acid sequences associated with serum extracellular vesicle (EV) preparations at the time of OS diagnosis, as a step towards an OS early detection assay. Sequencing of small nucleic acids extracted from serum EV preparations revealed increased representation of diverse repetitive element sequences in OS patient versus control sera. Analysis of a validation cohort using qPCR of PEG-precipitated EV preparations revealed the over-representation of HSATI, HSATII, LINE1-P1, and Charlie 3 at the DNA but not RNA level, with receiver operating characteristic (ROC) area under the curve (AUC) ≥ 0.90. HSATI and HSATII DNAs co-purified with EVs prepared by precipitation and size exclusion chromatography but not by exosome immunocapture, indicative of packaging in a non-exosomal complex. The consistent over-representation of EV-associated repetitive element DNA sequences suggests their potential utility as biomarkers for OS and perhaps other cancers. [ABSTRACT FROM AUTHOR]

The linear stability analysis on the WENO5 spatial discretization for solving the one-dimensional linear advection equation, combined with various fifth-order multistep methods, was presented in Motamed et al. (J Sci Comput 47(2):127–149, 2011). The purpose of this work is to further investigate the mechanism of oscillations observed in these time integrators when simulating shock front propagation. In particular, extrapolated backward differentiation formula (eBDF5), explicit Adams methed (Adams5) and a predictor–corrector method (PC5) are selected for detailed performance comparison. We first analyze how the non-convex combinations involved in these multistep methods restrict the time step-size and lead to possible pointwise oscillations. Subsequently, the nonlinear weights in the WENO5 scheme are used as indicators to capture the evolution of discontinuities with time and determine the stability of the multistep methods. Numerical results are also provided to confirm the analysis and review the qualifications of these multistep methods for shock front tracking. [ABSTRACT FROM AUTHOR]

Background: This study compares the impact of open (OIHR) versus laparoscopic (LIHR) inguinal hernia repair on healthcare spending and postoperative outcomes.Methods: The TRUVEN database was queried using ICD9 procedure codes for open, laparoscopic, and robotic-assisted IHR, from 2012 to 2013. Patients > 18 years of age and continuously enrolled for 12 months postoperatively were included. Demographics, patient comorbidities, postoperative complications, pain medication use, length of hospital stay, missed work hours, postoperative visits, and overall expenditure were collected, and assessed at time of surgery and at 30-, 60-, 90-, 180-, and 365-days postoperatively. Statistical analysis was conducted using SAS, with α = 0.05.Results: 66,116 patients were included (LIHR: N = 23,010; OIHR: N = 43,106). Robotic-assisted procedures were excluded due to small sample size (N = 61). The largest demographic was males between 55 and 64 years. LIHR had fewer surgical wound complications than OIHR (LIHR: 0.3%; OIHR: 0.5%, p = 0.007), less utilization of pain medication (LIHR: 23.3%; OIHR: 28.5%; p < 0.001), and fewer outpatient visits. In the 90-day postoperative period, LIHR had significantly fewer missed work hours (LIHR: 12.1 ± 23.2 h; OIHR: 12.9 ± 26.7 h, p = 0.023). LIHR had higher postoperative urinary complications (LIHR: 0.2%; OIHR: 0.1%; p < 0.001), consistent with the current literature. LIHR expenditures ($15,030 ± $25,906) were higher than OIHR ($13,303 ± 32,014), p < 0.001.Conclusions: The results highlight the benefits of laparoscopic repair with regard to surgical wound complications, postoperative pain, outpatient visits, and missed work hours. These improved outcomes with respect to overall healthcare spending and employee absenteeism support the paradigm shift toward laparoscopic inguinal hernia repairs, in spite of higher overall expenditures. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the influence of the immediate post-operative change in disc space angle relative to preoperation on heterotopic ossification (HO) occurrence following cervical disc arthroplasty (CDA) and on clinical and radiographic outcomes.Methods: Eighty-four patients with single-level Prestige-LP arthroplasty were retrospectively reviewed. HO was assessed based on McAfee classification. Radiological parameters, including index disc space angle (DSA), functional spinal unit angle, cervical lordosis, segmental range of motion (SROM), migration and subsidence of the prosthesis, prosthesis-endplate coverage ratio, and complications, were evaluated. Clinical features and outcome scores were also evaluated.Results: A significant association between immediate post-operative DSA change and HO occurrence was found. Patients with a more than 5° increase in immediate post-operative DSA lordosis had a significantly higher incidence of HO and more severe HO than patients with a less than 5° DSA increase after CDA. No correlation was observed between clinical outcomes and post-operative DSA increase or HO occurrence. Both groups maintained cervical sagittal alignment. However, patients with a more than 5° DSA increase exhibited larger anterior migration amount and lower prosthesis-endplate coverage ratio compared to a less than 5° increase in DSA, and more lordotic DSA and less SROM at the final follow-up compared with those at preoperation. No significant difference in other complications was found between the groups.Conclusion: Patients with a more than 5° increase in immediate post-operative DSA showed adverse effects on HO formation. Overcorrected DSA was associated with poor prosthesis stability, inadequate endplate coverage, and limited SROM, although it did not affect the clinical outcomes. These slides can be retrieved under Electronic Supplementary Material. [ABSTRACT FROM AUTHOR]

Introduction: Mortality rates from various cancer types are higher in patients with hyperglycaemia-associated pathologies. Among antineoplastics for treating pancreatic carcinoma, doxorubicin was found to be top of the list for inducing hyperglycaemia-related adverse drug reactions. Methods: Individual case safety reports of doxorubicin-induced hyperglycaemia-related adverse drug reactions (HG-ADRs) submitted during the period 2000–2017 were extracted from VigiBase®. Factors influencing outcome seriousness in these cases were analyzed using bivariate correlation and logistical regression. Age was stratified into five groups. Results: Among the 558 cases with high blood glucose included in this study, with an average patient age of 55.9 ± 14.3 years, 71.1% had serious outcomes and 10.9% died. Three factors—died, age, and gender—were all found to be significantly correlated with outcome seriousness (P < 0.01), while five factors—year reported, ADR duration, latency, treatment duration, and dosage—showed no correlation with outcome seriousness (P > 0.05). Identical conclusions were reached upon analyzing only the cases that did not involve corticosteroid use. Conclusion: Age and gender are risk factors for doxorubicin-induced serious HG-ADRs; males and older patients are more likely to suffer a serious outcome following such a reaction. [ABSTRACT FROM AUTHOR]

Background: Opioids are a mainstay for postsurgical pain management, but have associated complications and costs, and contribute to the opioid epidemic. While efforts to reduce opioid use exist, little study has been done on opioid utilization and its impact across surgical approaches. Our goal was to evaluate the impact of opioid utilization on quality measures and costs after open and laparoscopic colorectal surgery.Methods: The Premier database was reviewed for inpatient colorectal procedures from January 01, 2014, to September 30, 2015. Procedures were stratified into open and laparoscopic approaches, then "opioid" and "opioid-free" groups within each approach. Univariate analysis compared demographics, outcomes, and cost by opioid use and surgical approach. In the "opioid" groups, opioid consumption and duration were assessed across platforms. Multivariate regression analyzed the association between opioid use and surgical approach on costs and quality outcomes.Results: 50,098 procedures were evaluated-40.4% laparoscopic and 59.6% open. 6.6% of laparoscopic and 5.3% of open cases were "opioid free." Across both approaches, patients over 65 were most likely opioid free, while the obese and cancer patients were most likely to use opioids. Length of stay was shorter, and post-discharge nursing needs and total costs were lower in the "opioid-free" group in both approaches (all p < 0.001). The median daily and total opioid consumption were lower with a laparoscopic approach (p < 0.001), which also had a shorter duration of use versus open cases (p < 0.001). Opioids were 20% more likely in open cases. Total costs were 16% greater with opioids and 24% greater in open surgery. Complications were 89% more likely in open surgery. Readmissions were increased by 14% with both opioid use and open surgery.Conclusions: Opioid-free colorectal surgery results in improved outcomes, and laparoscopy further improves these results. Continued efforts to increase laparoscopy are key for reducing opioids and improving outcomes as we transition to value-based care. [ABSTRACT FROM AUTHOR]

Purpose: Autoantibody to 14-3-3 zeta was identified in gastric cancer (GC) by serological proteome analysis (SERPA) in our previous study. We comprehensively evaluated its ability to detect GC, determined its association with clinical characteristics, and explored its temporal change in GC patients before and after gastrectomy resection in this study. Methods: Anti-14-3-3 zeta antibody was examined by immunoassay in sera from 465 GC patients and 465 normal individuals, and also in 69 serial sera from 26 GC patients before and after resection. Results: The frequency of anti-14-3-3 zeta were significantly higher in GC group than in control group, with AUC of 0.627. The appearance of anti-14-3-3 zeta showed no difference in different tumor stage, tumor size, tumor differentiation, and lymphatic metastasis, but was higher in GC patients with family tumor history than without family tumor history. When anti-14-3-3 zeta was combined with clinical markers (CEA, CA199 and CA724), the sensitivity increased to 52.7%. In the follow-up analysis, the titer of anti-14-3-3 zeta was higher in post-resection sera than pre-resection sera, and no difference was observed in CEA, CA199 and CA724. Anti-14-3-3 zeta showed an increase from negative status to positive status in six patients after resection, while other three clinical markers presented different change in GC patients after resection. Conclusions: Autoantibody against 14-3-3 zeta could be a potential diagnostic biomarker and improve the sensitivity of CEA, CA199 and CA724 in diagnosis of GC. Further largescale studies will be needed to validate its performance in GC patients after resection. [ABSTRACT FROM AUTHOR]

The efficacy of oncolytic herpes simplex virus (oHSV) is limited by rapid viral clearance by innate immune effector cells and poor intratumoral viral spread. We combine two approaches to overcome these barriers: inhibition of natural killer (NK) cells and enhancement of intratumoral viral spread. We engineered an oHSV to express CDH1, encoding E-cadherin, an adherent molecule and a ligand for KLRG1, an inhibitory receptor expressed on NK cells. In vitro, infection with this engineered virus, named OV-CDH1, induced high surface E-cadherin expression on infected glioblastoma (GBM) cells, which typically lack endogenous E-cadherin. Ectopically expressed E-cadherin enhanced the spread of OV-CDH1 by facilitating cell-to-cell infection and viral entry and reduced viral clearance by selectively protecting OV-CDH1-infected cells from KLRG1+ NK cell killing. In vivo, OV-CDH1 treatment substantially prolonged the survival in GBM-bearing mouse models, primarily because of improved viral spread rather than inhibition of NK cell activity. Thus, virus-induced overexpression of E-cadherin may be a generalizable strategy for improving cancer virotherapy. [ABSTRACT FROM AUTHOR]

High-purity silicon power was doped with standard solutions containing 15 elements, and a high-purity indium tablet was prepared by the melting of indium pellets. An In-Si tablet, which is mechanically stable and thus suitable as a calibration sample, was prepared by our pressing the doped silicon power on the high-purity indium tablet. The matrix effect was studied by our investigating the variations of measured mass fractions (standard relative sensitivity factor, StdRSF, calibration) of doped impurities in the In-Si tablet, which provides a series of matrixes with different mass ratios of In to Si. For all the elements, the relative standard deviations of the measured mass fractions of impurities were less than 30%. The RSFs of the glow discharge mass spectrometer (Element GD) were obtained, and the results showed that three RSFs derived from the In-Si tablet with low, intermediate and high mass ratios of In to Si, respectively, agreed with the mean RSF within an uncertainty interval of 30%. The measurement of Fe and Al matrix certified reference materials further demonstrated that the RSFs generated from a matrix can be used for the calibration of another matrix, and the uncertainty was within 30%. Finally, another doped silicon powder was measured with the glow discharge mass spectrometer, which was calibrated by the mean RSFs from the In-Si tablet, and the analytical results obtained by glow discharge mass spectrometry are in good agreement with the analytical results obtained by high-resolution inductively coupled plasma mass spectrometry.ᅟ [ABSTRACT FROM AUTHOR]

Background: Introduction of the category III CPT code (0437T) for prophylactic mesh augmentation (PMA) highlights efforts to reduce incisional hernia (IH). PMA's value in the context of value-based care requires understanding both the cost of IH development and the savings from prevention. We hypothesized large healthcare costs with IH development. Appreciating which subsets of patients are at highest risk for IH, and the subsets who have the costliest care is essential in targeting interventions for hernia prevention.Methods: Retrospective cohort study utilizing data from Truven Health Analytic MarketScan Commercial Claims and Encounters Database from calendar years 2011-2014. Adults undergoing open abdominal operations with continued enrollment 3-year post-surgery were included. Inpatient and outpatient claims were tracked over 3 years to identify IH. Quantile regression estimated the association between conditional distribution of total cost and IH. A generalized linear model with gamma distribution estimated the association of conditional mean of total cost and IH. Models were adjusted for confounding cost covariates (e.g., age, gender, obesity, smoking, cancer).Results: 14,290 patients were identified, 1294 (9.1%) developed IH, 48% within 1-year, 33% at 1-2 years, and 19% at 2-3 years post-surgery. 515 underwent stoma creation, 4579 colon resection, 2263 liver/kidney, 3890 peritoneal, 3043 other (foregut, appendectomy, cholecystectomy). Rate of IH formation was 25, 13, 5.9, 6.3, and 6.3%, respectively. The difference in median expenditures for IH development versus no IH was ostomies: $26,098, colorectal: $21,211, liver/kidney: $23,811, peritoneal: $25,554, others: $28,870 (p < 0.0.01). IH within 1 year was more expensive than within 3 years in the following categories: colorectal ($16,034, p = 0.0385), liver/kidney ($27,145, p = 0.0004), and ostomy ($18,992, p = 0.0035).Conclusion: IH is a common occurrence imposing significant healthcare burden. Higher costs occur when IH occurs within 1 year versus 3 years from the index-procedure. This highlights the importance of hernia prevention techniques and the question of whether temporizing closure adjuncts  are appropriate in high-risk patients. [ABSTRACT FROM AUTHOR]

The quantitative structure-property relationship (QSPR) methodology was applied to describe and seek the relationship between the structures and energetic properties (and sensitivity) for some common energy compounds. An extended series of structural and energetic descriptors was obtained with density functional theory (DFT) B3LYP and semi-empirical PM3 approaches. Results indicate that QSPR model constructed using quantum descriptors can be applied to verify the confidence of calculation results compared with experimental data. It can be extended to predict the properties of similar compounds. [ABSTRACT FROM AUTHOR]

Microcystins (MCs) produced by cyanobacteria can accumulate in freshwater fish tissues and pose potential risk to human health. In this study, variations in MC content were examined in water samples and fish tissues during a Microcystis aeruginosa-dominated bloom in a fish pond in China, from June 2009 to August 2009. A total of ten microcystin variants were detected in water samples in the fish pond, including MCLR, MCRR, MCYR, MCLF, MCLY, MCLA, and MCLW, and other three undefined MC variants. MCLR was the dominant variant in the water samples, followed by MCLF and MCLY. The highest MC concentration in the common carp ( Aristichthys nobilis) was found in the order intestine > spleen > muscle; however, the order with the most MC variants detected was muscle > spleen = kidney = gallbladder > liver = intestine. The highest overall MC concentration detected in the water samples was 12.24 μg L, and the estimated daily intake for humans from the consumption of fish was about 0.48 μg MCLR eq kg body weight (BW), 12-fold the tolerable daily intake (TDI) proposed by the World Health Organization. Therefore, the combined risks from skin exposure and food intake in this fish pond should not be overlooked. [ABSTRACT FROM AUTHOR]

The toxicity and bioavailability of single arsenic species have been widely investigated, however, the biological effects of mixed arsenic species co-existing in natural waters still remain unknown. The objective of this work was to discern the adverse effects of combined arsenite (As(III)) and dimethylarsenic acid (DMA) on diatom Nitzschia palea. The combined ecotoxicity of As(III) and DMA on N. palea was observed to be time-dependent and showed dose-effect relation. The toxicity of DMA and As(III) mixture was higher than individual DMA or As(III) when the As(III) concentration was in the range of 0.085-0.316 mg L. As the As(III) concentration increased from 0.487 to 0.858 mg L, the antagonistic effect was found, which could be due to the higher thiols contents in the thiol-containing proteins (e.g., frustulins, silaffins and other glycoproteins). The content of malondialdehyde (MDA) in the treatment of mixed arsenic species was found to be at the same level compared to the As-free control after 72 h of exposure, indicating that the co-toxicity of As(III) and DMA on diatom frustules was not significant. Furthermore, the increase of frustule formation rate in the mixture of EC As(III)-EC DMA at 72 h exposure time indicated that the damaged diatom cell walls was likely repaired gradually. The results from this study suggested that the effects of co-existed arsenic species were concentration-specific and should be considered in the risk assessment of arsenic and development of water quality criteria for the protection of aquatic ecosystems. [ABSTRACT FROM AUTHOR]

A through-diffusion method was used to investigate the Re(VII) (as a surrogate to Tc(VII)) diffusion in compacted illite-, hematite- and limonite-montmorillonite mixtures. The effective diffusion coefficient D values were in the range of (4.29-6.71) × 10 m/s at pH 3.0 and (3.44-5.72) × 10 m/s at pH 9.0, respectively. Compared to montmorillonite, both D and α values enhanced at least three-folds in montmorillonite mixtures, indicating that the impurities changed the diffusion path. Interestingly, the K values of (0.63-3.94) × 10 kg/m were found in montmorillonite mixtures. However, the change of D value was less than two-folds, indicating that the illitization and iron corrosion of a back-fill material had no obvious influence on Re(VII) diffusion velocity. [ABSTRACT FROM AUTHOR]

Introduction: Opioid analgesic use is a major cause of morbidity and mortality in the US, yet effective treatment programs have a limited ability to detect relapse. The utility of current drug detection methods is often restricted due to their retrospective and subjective nature. Wearable biosensors have the potential to improve detection of relapse by providing objective, real time physiologic data on opioid use that can be used by treating clinicians to augment behavioral interventions. Methods: Thirty emergency department (ED) patients who were prescribed intravenous opioid medication for acute pain were recruited to wear a wristband biosensor. The biosensor measured electrodermal activity, skin temperature and locomotion data, which was recorded before and after intravenous opioid administration. Hilbert transform analyses combined with paired t-tests were used to compare the biosensor data A) within subjects, before and after administration of opioids; B) between subjects, based on hand dominance, gender, and opioid use history. Results: Within subjects, a significant decrease in locomotion and increase in skin temperature were consistently detected by the biosensors after opioid administration. A significant change in electrodermal activity was not consistently detected. Between subjects, biometric changes varied with level of opioid use history (heavy vs. nonheavy users), but did not vary with gender or type of opioid. Specifically, heavy users demonstrated a greater decrease in short amplitude movements (i.e. fidgeting movements) compared to non-heavy users. Conclusion: A wearable biosensor showed a consistent physiologic pattern after ED opioid administration and differences between patterns of heavy and non-heavy opioid users were noted. Potential applications of biosensors to drug addiction treatment and pain management should be studied further. [ABSTRACT FROM AUTHOR]

The article presents a retrospective study which examines the effect of the revised 2013 American Society of Clinical Oncology/College of American Pathologists (ASCO/CAP) guidelines on Human Epidermal Growth Factor Receptor 2 (HER2) results in core needle biopsies of invasive breast carcinoma. The study compared the guideline cohorts in 2007 and 2013. Results show the role of the guidelines in increasing the number of HER2 fluorescence in situ hybridization (FISH) equivocal biopsies.

Objective The objective of this study was to compare the prevalence of select preconception health indicators among women with and without disabilities. Methods 2010 Behavioral Risk Factor Surveillance System data were used to estimate the prevalence of health behaviors, health status indicators, and preventive health care among non-pregnant women ages 18-44 years with (N = 8370) and without (N = 48,036) disabilities. Crude percentages were compared with Chi square statistics. Multivariable logistic regressions adjusted for socio-demographic factors. Results Women with disabilities were more likely than women without disabilities to currently smoke (30.5 vs. 14.5 %, p < 0.0001) and less likely to exercise in the past month (67.1 vs. 79.8 %, p < 0.0001). Heavy drinking was similar in the two groups (4.4 vs. 4.5 %, p = 0.9). Health status indicators were worse among women with disabilities, with 35.0 % reporting fair/poor health and 12.4 % reporting diabetes, compared with 6.7 and 5.6 %, respectively, among women with no disabilities ( p < 0.0001 for both). Frequent mental distress, obesity, asthma, and lack of emotional support were also higher among women with disabilities compared with their non-disabled counterparts. Women with disabilities were more likely to receive some types of preventive care, (HIV), but less likely to receive others (recent dental cleaning, routine checkup). Disparities in health behaviors and health status indicators between the two groups remained after adjusting for socio-demographic factors. Conclusion Women with disabilities at reproductive age are more vulnerable to risk factors associated with adverse pregnancy outcomes compared to their counterparts without disabilities. Our findings highlight the need for preconception health care for women with disabilities. [ABSTRACT FROM AUTHOR]

Biosensor systems are increasingly promoted for use in behavioral interventions. Portable biosensors might offer advancement over self-report use and can provide improved opportunity for detection and intervention in patients undergoing drug treatment programs. Fifteen participants wore a biosensor wristband capable of detecting multiple physiologic markers of sympathetic nervous system (SNS) arousal for 30 days. Urine drug screening and drug use self-report were obtained twice per week. A parameter trajectory description method was applied to capture abrupt changes in magnitude of three measures of SNS activity: Electrodermal activity (EDA), skin temperature and motion. Drug use events detected by the biosensor were verified using a triad of parameters: the biosensor data, urine drug screens, and patient self-report of substance use. Twelve positive cocaine urine screens were identified. Thirteen self-reported episodes of cocaine use were recorded. Distinct episodes with biometric parameters consistent with cocaine use were identified on biosensor data. Eleven potential cocaine use episodes were identified by biosensors that were missed by both self-report and drug screening. Study participants found mobile biosensors to be acceptable, and compliance with the protocol was high. Episodes of cocaine use, as measured by supraphysiologic changes in biophysiometric parameters, were detected by analysis of biosensor data in instances when self-report or drug screening or both failed. Biosensors have substantial potential in detecting substance abuse, in understanding the context of use in real time, and in evaluating the efficacy of behavioral interventions for drug abuse. [ABSTRACT FROM AUTHOR]

The adverse consequences of postpartum depression on the health of the mother and her child are well documented. However, there is little information on postpartum depression among mothers with disabilities. This study examines the patterns of depression and depressive symptoms before, during and after pregnancy and the association between depression before and during pregnancy and postpartum depression symptomatology (PPD) among women with and without disabilities. Data from the 2009-2011 Rhode Island Pregnancy Risk Assessment Monitoring System (PRAMS) were analyzed in 2013. Almost 30 % (28.9 %; 95 % CI 22.8-35.8) of mothers with disabilities reported often or always feeling down, depressed or sad after childbirth compared to 10 % of those without disabilities (95 % CI 8.9-11.3). Compared to other women in the study, women with disabilities had a greater likelihood for PPD symptoms (RR 1.6, 95 % CI 1.1-2.2) after accounting for sociodemographics, maternal characteristics related to PPD, and depression before and during pregnancy. Adjusting for other covariates, self-reported prenatal diagnosis of depression was not associated with symptoms of PPD and depression during pregnancy was marginally associated with PPD symptomatology for women with disabilities. Women with disabilities are at a greater risk of experiencing symptoms of postpartum depression than other women. Screening for PPD among new mothers with disabilities and timely referral of those with PPD diagnosis are vital to the health of mothers with disabilities and their children. [ABSTRACT FROM AUTHOR]

Antibodies against tumor-associated antigens (TAAs) have been found in serum of patients with various types of cancers and may serve as biomarkers for early detection of esophageal cancer as well. This systematic review aims to give an overview about known autoantibodies and their diagnostic value in esophageal cancer. We conducted a systematic literature search in two databases to identify studies which performed serological testing for autoantibodies in esophageal cancer patients and controls. Data on study characteristics and results were extracted independently by two reviewers. Overall, 45 articles reporting the detection of 35 different autoantibodies met the inclusion criteria of this review. The most common antibody detection method was enzyme-linked immunosorbent assay (ELISA), and the most frequently assessed autoantibody was anti-p53, which was tested in 17 studies and for 15 studies of which a meta-analysis was conducted to comprehensively evaluate the diagnostic value. Most antibodies were assessed in only one study, and only few authors have evaluated the diagnostic value of combinations of multiple autoantibodies. For single autoantibodies, specificity was generally very high (median 98.3 %), but sensitivity was mostly rather low (median 26.7 %). For some autoantibody combinations, substantially higher sensitivity at reasonably high levels of specificity could be achieved. Development of extended and optimized multimarker panels of autoantibodies might be a promising approach for esophageal cancer early detection. [ABSTRACT FROM AUTHOR]

Esophageal cancer (EC) is the sixth leading cause of cancer-associated death worldwide and the incidence and mortality in China are the highest. The single nucleotide polymorphisms (SNPs) related to microRNAs could lead to alteration in microRNA expression and contribute to the susceptibility of cancer. To evaluate the association between microRNA-related SNPs and EC, a case-control study including 381 patients with esophageal squamous cell carcinoma (ESCC) and 426 gender, age-matched controls was carried out to investigate the genetic susceptibility of five microRNA-related SNPs (rs2910164 in microRNA-146a, rs11614913 in microRNA-196a-2, rs7813 in GEMIN4, rs1595066 and rs16845990 in ErbB4) as well as the interactions of gene-gene and gene-environment in the development of ESCC. Variant homozygote genotype of rs11614913 in microRNA-196a-2 and rs1595066 in ErbB4 were significantly associated with reduced ESCC risk (OR: 0.62, 95 % CI: 0.39-0.99 and OR: 0.38, 95 % CI: 0.24-0.61). The analysis of haplotypes in ErbB4 gene showed significant increased ESCC risk in GC and GT haplotypes (OR: 1.46, 95 % CI: 1.08-1.99 and OR: 1.33, 95 % CI: 1.10-1.62), and inversely reduced ESCC risk in AC and AT haplotypes with OR (95 % CI) of 0.75 (0.60-0.94) and 0.65 (0.49-0.86), respectively. These findings suggest that the polymorphisms in the microRNA-related genes may affect susceptibility of ESCC in Chinese Han population and the gene-gene interactions play vital roles in the progression on esophageal cancer. Future studies with larger sample and different ethnic populations are required to support and validate our findings. [ABSTRACT FROM AUTHOR]

Esophageal squamous cell carcinoma (ESCC), one of the leading causes of cancer death worldwide, occurs at a relatively high frequency in China. To investigate whether common excision repair cross-complementing rodent repair group 2 (ERCC2) variants (rs3916874 G>C, rs238415 C>G, rs1618536 G>A, rs1799793 G>A, and rsl3181 A>C) were associated with ESCC risk, a case-control study was conducted, including 405 cases with ESCC and 405 age and sex 1:1 matched cancer-free controls. The result showed that rsl3181 AC/CC genotypes was associated with an increased risk of ESCC (OR: 1.45, 95 % CI: 1.05-2.00), and two ERCC2 haplotypes GCGGC (Hap5) and GGAGC (Hap7) were associated with increased risk of ESCC (OR: 2.16, 95 % CI: 1.27-3.57 for Hap5 and OR: 3.72; 95 % CI: 1.89-6.63 for Hap7, respectively), while GGGGA (Hap4) was associated with decreased risk of ESCC (OR: 0.47, 95 % CI: 0.35-0.71). Gene-environment interaction analysis by multifactor dimensionality reduction (MDR) software showed that there was an interaction among rs238415, rs1618536, and family history of cancer with a P value under 0.0001 (OR: 3.23: 95 % CI: 2.37-4.40). These results suggested that genetic variations in the ERCC2 gene were associated with risk of ESCC, and there was a significant interaction between gene polymorphisms and family history of cancer in the etiology of ESCC. [ABSTRACT FROM AUTHOR]