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The incidence and mortality from colorectal cancer in younger adults (younger than 55 years) is increasing. We reviewed the complete database of a gene-expression test, Oncotype DX Colon Recurrence Score test, to determine age-related differences in recurrence score (RS) and single-gene results (7 cancer-related of the 12-gene assay). We included 20 478 stage II and III A and B colon cancer patients submitted to Genomic Health. RS results were grouped by low-, intermediate-, and high-risk groups. Single-gene scores were described using median and interquartile range. Of all patients 72.5% and 72.6% of those younger than 40 years had low-risk RS. Comparing older with younger patients, RS or single-gene expression did not differ by age group or stage. Young-onset colon cancer does not differ by expression of the RS component genes. Most patients with stage II and III colon cancer have low-risk disease as measured by the 12-gene assay, regardless of age. [ABSTRACT FROM AUTHOR]

Abstract Background In patients with stage IV colorectal cancer (CRC), minimally invasive surgery (MIS) may offer optimal oncologic outcome with low morbidity. However, the relative benefit of MIS compared to open surgery in patients requiring multistage resections has not been evaluated. Methods Patients who underwent totally minimally invasive (TMI) or totally open (TO) resections of CRC primary and liver metastases (CLM) in 2009–2016 were analyzed. Inverse probability of weighted adjustment by propensity score was performed before analyzing risk factors for complications and survival. Results The study included 43 TMI and 121 TO patients. Before and after adjustment, TMI patients had significantly less cumulated postoperative complications (41% vs. 59%, p = 0.001), blood loss (median 100 vs. 200 ml, p = 0.001) and shorter length of hospital stay (median 4.5 vs. 6.0 days, p < 0.001). Multivariate analysis identified TO approach vs. MIS (OR = 2.4, p < 0.001), major liver resection (OR = 4.4, p < 0.001), and multiple CLM (OR = 2.3, p = 0.001) as independent risk factors for complications. 5-year overall survival was comparable (81% vs 68%, p = 0.59). Conclusion In patients with CRC undergoing multistage surgical treatment, MIS resection contributes to optimal perioperative outcomes without compromise in oncologic outcomes. Synopsis: A coordinated preplanned approach to total laparoscopic multistage resection of stage IV colorectal cancer optimizes short-term outcomes. [ABSTRACT FROM AUTHOR]

Emerging evidence indicates a link between the increased proportion of regulatory T cells (Tregs) and reduced survival in patients who have been diagnosed with cancer. Cancer stem cells (CSCs) have been indicated to play a vital role in tumour initiation, drug resistance and recurrence. However, the relationship between Tregs and CSCs remains largely unknown. Here, we sorted out ovarian cancer stem-like side population (SP) cells and CD133+ cells to investigate the influence of ovarian CSCs on Tregs. Among the various immune-related molecules that we assessed, C-C motif chemokine ligand 5 (CCL5) was the most elevated in ovarian CSCs relative to that in the non-CSCs. The expression of its receptor, C-C motif chemokine receptor 5 (CCR5), was also increased on the surface of Tregs in ovarian cancer patients. This receptor-ligand expression profile indicated that ovarian CSCs recruit Tregs via CCL5-CCR5 interactions. We further assessed the expression of interleukin (IL)-10 in Tregs cultured with different cancer cells. Tregs cultured in conditioned medium (CM) from ovarian CD133+ cells expressed a higher level of IL-10 than Tregs cultured in CM from CD133- cells, indicating that Tregs exert pronounced immune-inhibitory functions in CSC-rich environments. Furthermore, co-culture with ovarian cancer cell lines induced the expression of matrix metalloproteinase-9 (MMP9) in Tregs which, in turn, enhanced the degradation of the extracellular matrix and enabled the invasion of tumour cells, thereby facilitating tumour metastasis. For the first time, to our knowledge, our findings describe the relationship between ovarian CSCs and Tregs, and demonstrated that these two cell populations co-operate to promote tumour immune tolerance and enhance tumour progression. [ABSTRACT FROM AUTHOR]

Taro ( Colocasia esculenta ) is an important crop in Africa, Southeast Asia and the subtropics, as it is used for food and medicine. The aims of this study were to access a large expression datasets of taro and reveal the candidate genes of starch synthesis. As a result, approximately 2.2 Gb sequence data of taro transcriptome were obtained by using Illumina HiSeq 2000 platform and assembled into 52,935 contigs with an average length of 588.5 bp. Sequence similarity analyses against four public databases (NR, GO, KEGG, KOG) found 17,047 contigs that could be annotated with gene descriptions, conserved protein domains, or gene ontology terms. Among the important metabolic pathways, 26 genes related to starch synthesis were validated by RT-PCR. This transcriptome dataset can serve as an important public information platform for further studies in gene expression, genomics, and functional genomic studies in C. esculenta . [ABSTRACT FROM AUTHOR]

Malignant transformation of normal hematopoietic transplants induced by residual leukemia cells is considered as a pivotal mechanism of donor cell leukemia (DCL). The effects of leukemia cell-derived microvesicles (MVs) in this transformation were examined. We found that MVs derived from K562 leukemia cells contained the breakpoint cluster region-Abelson leukemia gene human homolog 1 (BCR-ABL1) mRNA. Following incubation with BCR-ABL1-positive MVs, mononuclear cells derived from normal transplants exhibited a leukemia-like malignant phenotype both in vitro and in vivo. Horizontal transfer of BCR-ABL1 mRNA from MVs into the recipient cells was critical to the transformation. Relative genomic instability was observed and considered the main mechanism in the recipient cells. MVs contributed to genomic instability by two distinct pathways: via consequent overexpression of activation-induced cytidine deaminase and reactive oxygen species, which mediated DNA breakage and recombination; and via upregulation of methyltransferases and global DNA hypermethylation. We demonstrated that BCR-ABL1-positive MVs could initiate malignant transformation of normal hematopoietic transplants through genomic instability, which might serve as a convenient and operable model for investigating leukemogenesis, especially for DCL. Furthermore, MVs themselves could act as an early warning indicator and a novel tool to detect and prevent the occurrence of DCL. [ABSTRACT FROM AUTHOR]

Malignant transformation of normal hematopoietic transplants induced by residual leukemia cells is considered as a pivotal mechanism of donor cell leukemia (DCL). The effects of leukemia cell-derived microvesicles (MVs) in this transformation were examined. We found that MVs derived from K562 leukemia cells contained the breakpoint cluster region-Abelson leukemia gene human homolog 1 (BCR-ABL1) mRNA. Following incubation with BCR-ABL1-positive MVs, mononuclear cells derived from normal transplants exhibited a leukemia-like malignant phenotype both in vitro and in vivo. Horizontal transfer of BCR-ABL1 mRNA from MVs into the recipient cells was critical to the transformation. Relative genomic instability was observed and considered the main mechanism in the recipient cells. MVs contributed to genomic instability by two distinct pathways: via consequent overexpression of activation-induced cytidine deaminase and reactive oxygen species, which mediated DNA breakage and recombination; and via upregulation of methyltransferases and global DNA hypermethylation. We demonstrated that BCR-ABL1-positive MVs could initiate malignant transformation of normal hematopoietic transplants through genomic instability, which might serve as a convenient and operable model for investigating leukemogenesis, especially for DCL. Furthermore, MVs themselves could act as an early warning indicator and a novel tool to detect and prevent the occurrence of DCL. [ABSTRACT FROM AUTHOR]

We investigate high-power terahertz (THz) generation in two-color laser filamentation using terawatt (TW) lasers including a 0.5TW, 1 kHz system, as well as 2 and 30TW systems both operating at 10 Hz. With these lasers, we study the macroscopic effect in filamentation that governs THz output energy yields and radiation profiles in the far field. We also characterize the radiation spectra at a broad range of frequencies covering radio-micro-waves to infrared frequencies. In particular, our 1 kHz THz source can provide high-energy (>1μJ), high average power (>1 mW), intense (>1MVcm-1) and broadband (0.01-60 THz) THz radiation via two-color filamentation in air. Based on our scaling law, an ~30TW laser can produce >0.1 mJ of THz radiation with multigigawatt peak power in ~1.5m long filamentation. [ABSTRACT FROM AUTHOR]

This study analysed the resistance and susceptibility of several barley cultivars harbouring one of six resistance genes ( rym1-6) to Japanese Barley yellow mosaic virus (BaYMV) isolate JK05 using infectious RNA transcripts. At the cellular level, the virus replicated efficiently in mesophyll protoplasts from rym3 cultivars, less efficiently in protoplasts from a rym2 cultivar and poorly or not at all in protoplasts from other rym cultivars. None of the rym cultivars was susceptible at the whole-plant level. These results indicate that rym2 and rym3 cultivars are resistant to this virus isolate at the movement level, whereas the other rym cultivars are resistant at the cellular level. In addition, among five barley cultivars without known resistance genes, it was found that the cv. Haruna Nijo was resistant to this virus isolate at the cellular level. Based on the host responses, it was inferred that the BaYMV isolate JK05 is in the Japanese pathotype II group. A possible mechanism for how resistance-breaking variants continually emerge in fields is discussed. [ABSTRACT FROM AUTHOR]

Abstract: Carbon and nitrogen are the most frequent foreign interstitial atoms in α-Fe. The presence of even a little amount of these impurities in interstitial positions has a drastic influence on the properties of steels. However, the physics of the C–N interaction remains unclear. Here we perform first-principles calculations based on the density functional theory to study the interactions of C–N and those with vacancy (□) in α-Fe. When C and N atoms are in neighbor octahedral sites, a hybridization around −8eV of C 2p states with the N 2p states is observed. C and N atoms lie as far away from one another as possible. When a vacancy is introduced, it can attract two C atoms and a N atom, and a C–C–N–□ complex is formed. When the C and N atoms are the first nearest neighbors of the vacancy and stay in two neighbor octahedral sites, a covalent C–N bond is formed. And the peak of 2p states of the C atom’s density of states shifts to around −8eV, where the peak of the N atom’s 2p states lies. [Copyright &y& Elsevier]

Attempts to associate methylenetetrahydrofolate reductase (MTHFR) gene C677T polymorphism with hypertension have been extensively evaluated, but mostly in Caucasians. We therefore meta-analysed this polymorphism in association with hypertension and hypertension-in-pregnancy (HIP) among Chinese subjects. A random-effects model was applied irrespective of between-study heterogeneity, which was evaluated by subgroup and meta-regression analyses. Study quality was assessed in duplicate. Publication bias was weighed using Egger's test and funnel plot. Data on 20 qualified studies totalling 4461 Chinese subjects were meta-analysed. In overall allelic/genotypic models, carriers of 677T or 677TT were consistently at significantly increased risk of developing hypertension and HIP. No between-study heterogeneity was identified for all genetic models, with the exception for contrast of allele 677T versus 677C in hypertension association studies (P=0.03), and the dominant contrast in HIP association studies (P=0.025). Both the subgroup and meta-regression analyses indicated that study design was a potential source of between-study heterogeneity. Funnel plot and Egger's test suggested no evidence of publication bias. Taken together, our results supported the notion that carriers of 677T or 677TT were at significantly increased risk of developing hypertension and HIP, but indicated caution in interpreting this result, because the study design made marginal significant contribution to the heterogeneity. [ABSTRACT FROM AUTHOR]

We report the phase-resolved spectral results of the first Galactic pulsating ultraluminous X-ray source (PULX) Swift J0243.6+6124, modeling its 2017–2018 outburst peak using data collected by the Hard X-ray Modulation Telescope (Insight-HXMT). The broad energy coverage of Insight-HXMT allows us to obtain a more accurate spectral continuum to reduce the coupling of broad iron line profiles with other components. We use three different continuum spectrum models but obtain similar iron line results. For the first time, we detect the pulse characteristics of the broad iron line in a PULX. The variation in the width and intensity of this iron line with σ ∼ 1.2–1.5 keV has a phase offset of about 0.25 from the pulse phase. We suggest that the uneven irradiation of the thick inner disk by the accretion column produces the modulated variation of the broad iron line. In addition, the nonpulsed narrow line is suggested to come from the outer disk region. [ABSTRACT FROM AUTHOR]

A combination of orthogonal frequency division multiplexing (OFDM) with frequency-division multiple access (FDMA) called OFDMA is regarded as a promising solution for improving the performance of interactive wireless broadcasting systems. This work focuses on the performance of OFDM when used as a modulation and access technique for the uplink of an interactive wireless broadcasting system. In such an application, we present our investigations of the effects of symbol timing misalignments and peak-to-average power ratio (PAR). Under the condition of the same side information bits, the selective mapping (SLM) approach can be implemented by decimating OFDM samples, which is less complex compared to the ordinary SLM incurring a slight degradation of the PAR performance. Taking into account the effects of clipping operation and symbol timing misalignment, the bit error rate (BER) and throughput performances are investigated for a typical OFDMA uplink scenario. [ABSTRACT FROM AUTHOR]

Orthogonal frequency-division multiple access (OFDMA), which is a combination of orthogonal frequency division multiplexing (OFDM) with frequency-division multiple access (FDMA), is regarded as a promising solution for enhancing the performance of interactive broadcasting wireless systems. This paper presents our investigation for the impacts of symbol timing errors and peak-to-average power ratio (PAR) on OFDMA-based interactive broadcasting systems. Under the condition of the same side information bits, the selective mapping (SLM) approach can be implemented by decimating OFDM samples, which is less complex compared to the ordinary SLM incurring a slight degradation of the PAR performance. Including the effects of clipping operation and symbol timing misalignment, the bit error rate (BER) performance is investigated for a typical OFDMA uplink scenario. [ABSTRACT FROM AUTHOR]

Reproducing kernel, with its intrinsic feature of moving averaging, can be utilized as a low-pass filter with scale decomposition capability. The discrete convolution of two nth order reproducing kernels with arbitrary support size in each kernel results in a filtered reproducing kernel function that has the same reproducing order. This property is utilized to separate the numerical solution into an unfiltered lower order portion and a filtered higher order portion. As such, the corresponding high-pass filter of this reproducing kernel filter can be used to identify the locations of high gradient, and consequently serves as an operator for error indication in meshfree analysis. In conjunction with the naturally conforming property of the reproducing kernel approximation, a meshfree adaptivity method is also proposed. [ABSTRACT FROM AUTHOR]

Describes a model for three-phase transformers with three legs with and without tank under direct current bias based on electric and magnetic circuit theory. Calculation of the nonsinusoidal no-load currents in time and frequency domain; Influence of tank; Magnetic history of transformer magnetization; Residual magnetism; Wave shapes of the three magnetizing currents.

Simple Summary: While anti-PD1 antibodies have demonstrated efficacy in some patients with metastatic anal cancer, these agents have no proven benefit for those with localized disease treated with chemoradiation. Difficulty procuring fresh tumor tissue required for RNA and protein expression analysis has limited extensive molecular profiling for this rare cancer. Our team utilized a novel digital spatial profiling technology on pretreatment anal cancer specimens to identify biomarkers associated with recurrence after chemoradiation. We observed that recurrent tumors had higher baseline expression of immune checkpoint biomarkers, higher MAPK signaling activation and higher PI3K/Akt signaling activation. These findings provide a rationale that supports future clinical trials with immunotherapy that seek to improve survival beyond chemoradiation for patients with localized squamous cell cancer of the anus. The identification of transcriptomic and protein biomarkers prognosticating recurrence risk after chemoradiation of localized squamous cell carcinoma of the anus (SCCA) has been limited by a lack of available fresh tissue at initial presentation. We analyzed archival FFPE SCCA specimens from pretreatment biopsies prior to chemoradiation for protein and RNA biomarkers from patients with localized SCCA who recurred (N = 23) and who did not recur (N = 25). Tumor cells and the tumor microenvironment (TME) were analyzed separately to identify biomarkers with significantly different expression between the recurrent and non-recurrent groups. Recurrent patients had higher mean protein expression of FoxP3, MAPK-activation markers (BRAF, p38-MAPK) and PI3K/Akt activation (phospho-Akt) within the tumor regions. The TME was characterized by the higher protein expression of immune checkpoint biomarkers such as PD-1, OX40L and LAG3. For patients with recurrent SCCA, the higher mean protein expression of fibronectin was observed in the tumor and TME compartments. No significant differences in RNA expression were observed. The higher baseline expression of immune checkpoint biomarkers, together with markers of MAPK and PI3K/Akt signaling, are associated with recurrence following chemoradiation for patients with localized SCCA. These data provide a rationale towards the application of immune-based therapeutic strategies to improve curative-intent outcomes beyond conventional therapies for patients with SCCA. [ABSTRACT FROM AUTHOR]

We present an X-ray spectrum of the diffuse X-ray background (DXRB) between 1.5 and 120 keV, as measured with the Low-Energy Detector (LE) and the High-Energy Detector (HE) aboard the Insight-HXMT satellite, based on 'blank-sky' observations. LE covers a nominal energy range of 1–15 keV and HE 20–250 keV, but calibration issues and data quality narrowed the energy range for this work. The LE background was directly measured with 'blind' detector modules, while the HE background was derived from Earth-occultation data. With the LE data alone, the measured DXRB spectrum can be well-described by a power law; fitting the LE and HE data jointly, however, a spectral cut-off must be introduced in the model to account for the measurements above 30 keV. Modelling the combined spectrum with a cut-off power law, the best-fitting photon index is 1.40, normalization 9.57  |$\rm ph~cm^{-2}\,s^{-1}\,keV^{-1}\,sr^{-1}$| (at 1 keV), and cut-off energy 55 keV after correcting for the effects of the Earth albedo and atmospheric emission (which are significant in the HE band). Based on the best-fitting cut-off power law, we derived the spectral energy distribution (SED) of the DXRB. The shape of the SED is in general agreement with the published measurements, but the overall normalization is lower by varying amounts, except for the HEAO-1 result, with which our result is in good agreement. [ABSTRACT FROM AUTHOR]

Background: Colorectal cancer in young adults is on the rise. This rise combined with delayed childbearing increases the likelihood of colorectal cancer diagnosed during pregnancy or in the postpartum period. Methods: Electronic health records were used to identify individuals with colorectal cancer in pregnancy or the postpartum period from 1 August 2007 to 1 August 2019. Results: Forty-two cases were identified. Median age at diagnosis was 33 years. Most (93%) were diagnosed in an advanced stage (III or IV) and had left-sided colorectal cancer tumors (81%). Molecular analysis was completed in 18 (43%) women with microsatellite status available in 40 (95%). The findings were similar to historical controls. Sixty percent were diagnosed in the postpartum period. Common presenting symptoms were rectal bleeding and abdominal pain. Conclusion: Currently there is no consensus recommendation regarding how to manage colorectal cancer during pregnancy. Given the overlapping symptoms with pregnancy, patients often present with advanced disease. We encourage all health care professionals caring for pregnant women to fully evaluate women with persistent gastrointestinal symptoms to rule out colorectal cancer. [ABSTRACT FROM AUTHOR]

The joint National Aeronautics and Space Administration (NASA) and Japanese Aerospace Exploration Agency (JAXA) Global Precipitation Measurement (GPM) is a constellation mission, centered upon observations from the core satellite dual-frequency precipitation radar (DPR) and its companion passive microwave (MW) GPM Microwave Imager (GMI). One of the key challenges for GPM is how to link the information from the single DPR across all passive MW sensors in the constellation, to produce a globally consistent precipitation product. Commonly, the associated surface emissivity and environmental conditions at the satellite observation time are interpolated from ancillary data, such as global forecast models and emissivity climatology, and are used for radiative transfer simulations and cataloging/indexing the brightness temperature (TB) observations and simulations within a common MW precipitation retrieval framework. In this manuscript, the feasibility of an update to the surface emissivity state at or near the satellite observation time, regardless of surface type, is examined for purposes of assisting these algorithms with specification of the surface and environmental conditions. Since the constellation MW radiometers routinely observe many more nonprecipitating conditions than precipitating conditions, a principal component analysis is developed from the noncloud GMI-DPR observations as a means to characterize the emissivity state vector and to consistently track the surface and environmental conditions. The method is demonstrated and applied over known complex surface conditions to probabilistically separate cloud and cloud-free scenes. The ability of the method to globally identify 'self-similar' surface locations from the TB observations without requiring any ancillary knowledge of geographical location or time is demonstrated. [ABSTRACT FROM AUTHOR]

Purpose: Colon cancer surveillance guidelines do not routinely include positron emission tomography (PET) imaging; however, its use after surgical resection has been increasing. We evaluated the secular patterns of PET use after surgical resection of colon cancer among elderly patients and identified factors associated with its increasing use. Patients and Methods: We used the SEER-linked Medicare database (July 2001 through December 2009) to establish a retrospective cohort of patients age > 66 years who had undergone surgical resection for colon cancer. Postoperative PET use was assessed with the test for trends. Patient, tumor, and treatment characteristics were analyzed using univariable and multivariable logistic regression analyses. Results: Of the 39,221 patients with colon cancer, 6,326 (16.1%) had undergone a PET scan within 2 years after surgery. The use rate steadily increased over time. The majority of PET scans had been performed within 2 months after surgery. Among patients who had undergone a PET scan, 3,644 (57.6%) had also undergone preoperative imaging, and 1,977 (54.3%) of these patients had undergone reimaging with PET within 2 months after surgery. Marriage, year of diagnosis, tumor stage, preoperative imaging, postoperative visit to a medical oncologist, and adjuvant chemotherapy were significantly associated with increased PET use. Conclusion: PET use after colon cancer resection is steadily increasing, and further study is needed to understand the clinical value and effectiveness of PET scans and the reasons for this departure from guideline-concordant care. [ABSTRACT FROM AUTHOR]

By using the first-principles calculations within virtual crystal approximation (VCA) framework, the alloying behavior of transition metals M (M = Cr, Ni, Mo, V, Co, Nb, Mn, Ti and Cu) has been investigated in ternary ε-(Fe 1 − x M x ) 3 N nitrides ( x = 0–0.15). The phase stability and elastic properties are studied by calculating the formation Gibbs energy, independent elastic constants and densities of states. The calculated results show that the stability of the ε-(Fe 1− x M x ) 3 N nitrides decrease with the increase of the substitution content, indicating the decomposition of ε phase to α or γ′ phases. The elastic properties of the ε-(Fe 1− x M x ) 3 N nitrides are sensitive to the transition element types except Co and Mn which show the weakest effect. Densities of states are given for all ε-(Fe 1− x M x ) 3 N nitrides to confirm the origins of the variations of phase stability and elastic properties. The calculated results show a reasonable agreement with available experimental values. [ABSTRACT FROM AUTHOR]

Abstract: This article describes a comprehensive literature review of liquid entrainment in horizontal pipes with vertical-up branches. Deficiencies in the available data and correlations were identified. The Air–water Test Loop for Advanced Thermal–hydraulic Studies (ATLATS) was constructed and entrainment onset and steady-state data were collected for a wide range of flow conditions. Using new insights gained from experimental testing, the authors developed a model for predicting the onset of entrainment and steady-state entrainment rate. Previously published correlations, along with the new model, are compared against all available data. The new model shows very good agreement with the onset data, but is not very good at predicting branch quality at high liquid flow rates. [Copyright &y& Elsevier]

Background and purpose: Hereditary sensory and autonomic neuropathies (HSANs) are a group of clinically and genetically heterogeneous neurological disorders characterized by sensory dysfunctions. Here, 21 affected Chinese families are reported, including 19 with congenital insensitivity to pain with anhidrosis (CIPA; namely HSAN IV) and two with congenital insensitivity to pain (CIP; namely HSAN IID) caused by biallelic variations in NTRK1 and SCN9A, respectively, aiming to identify causative variants in these families and compare how different variants in NTRK1 affect the function of tropomyosin receptor kinase A (TrkA). Methods: Recombinant plasmids harboring the wild‐type and six mutant alleles (p.Gln216*, p.Glu584Lys, p.Leu595Arg, p.Pro684Leu, p.Val709Leu and p.Arg765Cys) of NTRK1 cDNA were constructed and transfected into HEK293 cells. Results: The results suggested that the five missense variants only presented a subtle influence on the expression level and glycosylation of TrkA but compromised the receptor phosphorylation. Our findings also suggested that a synonymous variant c.219C>T in NTRK1 may cause aberrant splicing, indicating a potential novel pathogenic mechanism of CIPA. Furthermore, gross deletion of SCN9A was first associated with CIP. Conclusions: This study identified multiple forms of variants responsible for CIPA/CIP in the Chinese population and might provide new insights into the pathogenesis of CIPA. [ABSTRACT FROM AUTHOR]

Reports on a high-efficiency energy transfer from both singlet and triplet states in a host material doped with the phosphorescent dye 2,3,7,8,12,13,18-octaethyl 21H,23H- porphine platinum (PtOEP). How the efficiency of electroluminescent organic light-emitting devices can be improved by the introduction of a fluorescent dye; Possible applications of the findings.

Introduction: Women with pathogenic germline gene variants in BRCA1 and/or BRCA2 are at increased risk of developing ovarian and breast cancer. While surgical and pharmacological approaches are effective for risk-reduction, it is unknown whether lifestyle approaches such as healthful dietary habits, weight management, and physical activity may also contribute to risk-reduction. We conducted a systematic review of evidence related to dietary habits, weight status/change, and physical activity on ovarian and breast cancer risk among women with BRCA1/2 pathogenic variants. Methods: We searched Medline, EMBASE, CENTRAL, PubMed, and clinicaltrials.gov up to October 3, 2019. We identified 2775 records and included 21. Results: There is limited evidence related to these factors and ovarian cancer risk. For breast cancer risk, evidence suggests higher diet quality, adulthood weight-loss of ≥10 pounds, and activity during adolescence and young-adulthood may be linked with decreased risk. Higher meat intake and higher daily energy intake may be linked with increased risk. Conclusions: There is not enough evidence to suggest tailored recommendations for dietary habits or weight management among women with BRCA1/2 pathogenic variants compared to the general population for ovarian and breast cancer risk-reduction, and physical activity recommendations should remain the same. [ABSTRACT FROM AUTHOR]

Laser micro-hole processing has been widely used in industry. Many laser processing parameters can affect the processing results. The relationship between the geometrical shapes of micro-holes and the laser processing parameters has not been determined accurately. In this paper, experiments on the femtosecond laser drilling of the nickel-base single-crystal super-alloy (DD6) materials were conducted to determine the relationship between the parameters, such as the laser single-pulse energy, rotation rate, and downward focus rate, and the geometrical characteristics of the micro-holes, such as the diameter, and roundness. A group of orthogonal experiments were conducted to determine the effects of the comprehensive influencing factors on the geometrical characteristics of the micro-holes. After the experiments were conducted and analysed, the experimental results were modelled by a backpropagation neural network, and the mapping relationship between the laser parameters and the geometrical morphologies of the micro-holes was constructed. The model established by the backpropagation neural network could obtain accurate prediction results, and the predictions of the diameters of the micro-holes were better than those of the roundness. [ABSTRACT FROM AUTHOR]

Background: Individuals who have colorectal or endometrial cancers displaying loss of immunohistochemical staining of one or more mismatch repair proteins without an identifiable causative germline pathogenic variant have unexplained mismatch repair deficiency (UMMRD). Comprehensive germline genetic testing for Lynch syndrome (LS) includes sequencing and deletion/duplication analysis of MLH1, MSH2, MSH6, and PMS2, deletion analysis of EPCAM, and MSH2 inversion analysis. Updated genetic testing to include elements of comprehensive LS testing not previously completed could further clarify LS status in individuals with UMMRD, allowing for tailored screening guidelines for affected individuals and their family members. However, patient understanding of the potential impact of updated genetic testing for LS is unclear. This study aimed to evaluate the interest in and perceived impact of updated genetic testing among individuals with UMMRD at a tertiary academic center. Methods: A survey evaluating interest in and perceived impact of updated genetic testing was mailed to 98 potential participants. Electronic health record review was completed for all individuals meeting eligibility criteria. Thirty-one individuals responded to the survey. Results: Results indicate this population is highly interested in updated genetic testing with the perceived impact being primarily for family members to have appropriate genetic testing and screening. Electronic health record review indicates that clinicians have an evolving understanding of causes of UMMRD, representing a potential change in assessment of cancer risk. Conclusions: Updated risk assessment and genetic counseling with a discussion of the benefits and limitations of germline and somatic genetic testing, is essential as the understanding of UMMRD and genetic testing recommendations for this population evolve. [ABSTRACT FROM AUTHOR]

A new experimental method for determining vapor-liquid equilibrium (VLE) of binary alloys was designed in this study. The VLE data of Pb-Sn and Sb-Sn alloys were determined by using this new method. The experimental data passed the thermodynamic consistency test (Van Ness test), and the y(MAD) was 0.4066 and 0.6667, respectively, indicating that the experimental method is correct and reliable. The activity coefficient of Pb-Sn and Sb-Sn alloys was calculated by using the molecular interaction volume model (MIVM). The maximum average relative deviation Si and maximum average standard deviation Si* are ±1.34% and ±0.009, respectively, which indicates that the calculation of the activity coefficient of the Pb- Sn and Sb-Sn alloys by MIVM is reliable. The VLE data of Pb-Sn and Sb-Sn alloys were calculated based on the VLE theory and MIVM, and the calculated results agreed well with the experimental VLE data. The VLE phase diagrams of Pb-Sn and Sb-Sn alloys were also established in this study. The VLE phase diagrams offer a valid and intuitive way to analyze the product compositions' dependence of temperature and pressure during the process of vacuum distillation. This will have immense significance in guiding the actual production of vacuum metallurgy. [ABSTRACT FROM AUTHOR]

Background and purpose The mechanism of retinal ganglion cell and retinal nerve fiber layer loss in multiple sclerosis ( MS) remains unknown. This study aimed to investigate the association between temporal retinal nerve fiber layer ( tRNFL) thinning and disease activity in the brain determined by T2 lesions on magnetic resonance imaging ( MRI). Methods Fifty-five consecutive patients with relapsing-remitting MS and 25 controls were enrolled. All patients underwent annual optical coherence tomography and high-resolution MRI scans for tRNFL thickness and brain lesion volume analysis, respectively. Results Significant tRNFL thickness reduction was observed over the 3-year follow-up period at a relatively constant rate (1.02 μm/year). Thinning of tRNFL fibers was more prominent in younger patients ( P = 0.01). The tRNFL loss was associated with new MRI lesions in the optic radiations ( ORs). There was significantly greater tRNFL thinning in patients with new lesional activity in the ORs compared with patients with new lesions outside the ORs ( P = 0.009). Conclusions This study supports the notion that retrograde transneuronal degeneration caused by OR lesions might play a role in progressive retinal nerve fiber layer loss. In addition, the results of the study also indicate that the disease-related neurodegenerative changes in the retina start much earlier than the clinical diagnosis of MS. [ABSTRACT FROM AUTHOR]

This study evaluated provider satisfaction in a sample of colorectal cancer ( CRC) survivors with and without Lynch syndrome ( LS). Participants were case-case-matched CRC survivors with ( n = 75) or without ( n = 75) LS (mean age of 55; range: 27-93). Participants completed a mailed questionnaire assessing demographics, clinical characteristics, healthcare utilization, psychosocial variables, and provider satisfaction. LS CRC survivors reported lower provider satisfaction scores on three subscales of the Primary Care Assessment Survey: communication (78.14 vs. 83.96; P < 0.05), interpersonal treatment (78.58 vs. 85.30; P < 0.05), and knowledge of the patient (60.34 vs. 69.86; P < 0.01). Among LS CRC survivors, predictors for mean communication and trust subscale scores were location of treatment and socioeconomic status. Higher mean depression scores also were associated with trust, while social support predicted higher satisfaction with communication. Sporadic CRC survivor satisfaction is driven largely by age (communication, interpersonal treatment) and patient anxiety (communication), while seeing a provider more often was associated with increased satisfaction with knowledge of the patient. LS CRC survivors reported lower levels of provider satisfaction than sporadic CRC survivors. LS survivors who received care at The University of Texas MD Anderson Cancer Center, a comprehensive cancer center ( CCC), reported higher satisfaction than those receiving care at other institutions. Depressive symptoms and socioeconomic status may impact provider satisfaction ratings. Exploration of other potential predictors of provider satisfaction should be examined in this population. Additionally, further research is needed to examine the potential impact of provider satisfaction on adherence to medical recommendations in LS CRC survivors, particularly those being treated outside of CCCs. [ABSTRACT FROM AUTHOR]

Based on the analysis of precision moulding mechanism for cylindrical gears with arcuate tooth trace (arc gear), the equation for tooth flank of arc gear was derived preliminarily and the ideal concave and convex tooth flanks were got by MATLAB simulation to achieve graphics rendering. On this basis, with UG NX8.0, the accurate three-dimensional modelling of arc gear was established to be used for the finite element analysis. Then, for the problem that there is no standardised bending strength calculation formula of arc gear, with the aid of finite element method (FEM) this paper studied the relationship between tooth line radius and bending strength. With FEM analysis performed, it was confirmed that under the same conditions, the bending strength of arc gear could be significantly improved compared with that of spur gear and helical gear, and that variation curve of tooth root stress was obtained under the different tooth line radius. Therefore, the analysis method provides engineering applications value under the high-speed and heavy-load working conditions and theoretical basis for the strength theory and design of arc gear. [ABSTRACT FROM AUTHOR]

Upregulation of the embryonic M2 isoform of pyruvate kinase (PKM2) emerges as a critical player in the cancer development and metabolism, yet the underlying mechanism of PKM2 overexpression remains to be elucidated. Here we demonstrate that IGF-1/IGF-IR regulates PKM2 expression by enhancing HIF-1α-p65 complex binding to PKM2 promoter. PKM2 expression is regulated by miR-148a/152 suppression. PKM2 directly interacts with NF-κB p65 subunit to promote EGR1 expression for regulating miR-148a/152 feedback circuit in normal cells, but not in cancer cells because of the DNA hypermethylation of miR-148a and miR-152 gene promoters. The silencing of miR-148a/152 contributes to the overexpression of PKM2, NF-κB or/and IGF-IR in some cancer cells. We show that disruption of PKM2/NF-κB/miR-148a/152 feedback loop can regulate cancer cell growth and angiogenesis, and is also associated with triple-negative breast cancer (TNBC) phenotype, which may have clinical implication for providing novel biomarker(s) of TNBC and potential therapeutic target(s) in the future. [ABSTRACT FROM AUTHOR]

Kabuki or Niikawa-Kuroki syndrome ( KS) is a rare disorder with multiple malformations and recurrent infections, especially otitis media. This study aimed to investigate the genetic defects in Kabuki syndrome and determine if immune status is related to recurrent otitis media. Fourteen patients from 12 unrelated families were enrolled in the 9-year study period (2005-2013). All had Kabuki faces, cleft palate, developmental delay, mental retardation, and the short fifth finger. Recurrent otitis media (12/14) and hearing impairment (8/14) were also more common features. Immunologic analysis revealed lower memory CD19+ cells (11/13), lower memory CD4+ cells (8/13), undetectable anti- HBs antibodies (7/13), and antibody deficiency (7/13), including lower IgA (4), IgG (2), and IgG2 (1). Naïve emigrant lymphocytes, lymphocyte proliferation function, complement activity, and superoxide production in polymorphonuclear cells were all normal. All the patients had KMT2D mutations and 10 novel mutations of R1252X, R1757X,Y1998C, P2550R fs2604X, Q4013X, G5379X, E5425K, R5432X, R5432W, and R5500W. Resembling the phenotype of common variable immunodeficiency, KS patients with antibody deficiency, decreased memory cells, and poor vaccine response increased susceptibility to recurrent otitis media. Large-scale prospective studies are warranted to determine if regular immunoglobulin supplementation decreases the frequency of otitis media and severity of hearing impairment. [ABSTRACT FROM AUTHOR]

Summary Interleukin-10 (IL-10) is a cytokine with anti-inflammatory and B-cell-stimulating activity. IL-10 is expressed in human atherosclerotic plaques and studies have shown the involvement of IL-10 in the atherosclerotic process. The IL-10−1082G/A polymorphism is one of the most commonly studied polymorphisms in this gene because of its association with coronary heart disease (CHD) risks, but previous results have been conflicting. We performed a meta-analysis using six eligible case-control studies (including 14 data sets) with a total of 5006 patients and 3968 controls to summarize the existing data on the association between the IL-10−1082G/A polymorphism and CHD risk. Compared with the common IL-10−1082G/A GG genotype, the carriers of variant genotypes ( IL-10−1082GA/AA) had a 1.12-fold elevated risk of CHD (95% CI = 1.01-1.23, P = 0.03) under the dominant genetic model, as estimated using a random effect model. The effect of the IL-10−1082G/A polymorphism was further evaluated using stratification analysis. In the three disease of artery studies, with the variant genotypes had a not obvious increased risk of disease of artery (OR = 1.19, 95% CI = 0.98-1.44, P = 0.08) as estimated using a fixed effect model. Similar results were found in the nine myocardial infarction studies (OR = 1.13, 95% CI = 1.00-1.27, P = 0.05). It was also demonstrated that the increased risk of CHD associated with IL-10−1082G/A variant genotypes was more pronounced in Caucasians (OR = 1.12, 95% CI = 1.01-1.23, P = 0.03). Our meta-analysis suggests that the IL-10−1082G/A polymorphism genotypes (GA+AA) might be associated with an increased risk of CHD, especially in Caucasians. [ABSTRACT FROM AUTHOR]

The effects of the turmeric ethyl acetate fraction (TEF) from the methanolic extract from Curcuma longa L. on lipid metabolism and underlying mechanisms of lipolysis were investigated in 3T3-L1 adipocytes. The intracellular lipid droplets were stained with Oil red O dye and quantified. Compared to the control, lipid accumulation was significantly decreased by 46.6% with treatment by TEF at the concentration of 20 microg/mL. The intracellular triglyceride (TG) level was also reduced by 37.9% at the concentration of 20 µg/mL. To determine the mechanism for TG content reduction, levels of glucose uptake and glycerol release were measured. Incubation of the 3T3-L1 adipocytes with TEF for 4 hours significantly lowered the cellular level of glucose in a dose-dependent manner. Furthermore, cellular expression of insulin-responsive glucose transporter (GLUT)-4 was decreased by 46%, indicating that reduced glucose uptake was due to a decrease in cellular GLUT-4 expression. In addition, the level of free glycerol released into the cultured medium was increased by 36.4% with the treatment by TEF. In subsequent measurements using quantitative real-time polymerase chain reaction, mRNA levels of hormone-sensitive lipase (HSL) and adipose TG lipase (ATGL) were elevated by 34.8% and 16.9%, respectively, at the concentration of 20 µg/mL. These results suggest that TEF partially inhibits lipogenesis by the suppression of glucose uptake via the decreased expression of cellular GLUT-4 and stimulates lipolysis through the induction of HSL and/or ATGL gene expression, resulting in the increased glycerol release. [ABSTRACT FROM AUTHOR]

Abstract: This paper presents the results of an experimental study on the interfacial bond strength of glass fiber reinforced polymer (GFRP) bars in high-strength concrete cube. The experimental program consisted of testing 54 concrete cube specimens prepared according to CSA S802-02 standard. Two main parameters were considered in the experimental investigation: the compressive strength of concrete (from 25.6MPa to 92.4MPa) and the type of rebar (steel, sand-coated GFRP, and helically wrapped GFRP). The test results showed that the interfacial bond strength of the GFRP bars increased as the compressive strength of concrete increased. However, the increasing rate of the bond strength of the GFRP bars with respect to the concrete strength was much smaller than that of the steel bars. The concrete specimens were sawn in half after the test for a closer investigation of the actual mode of bond failure. Visual examination of the specimens showed that bond failure of the steel bar was caused by concrete crushing against the face of the ribs, while bond failure of the GFRP bars occurred not only in the concrete but also in the bars by delamination of the resin-rich outer layer from the fiber core. The average area of the delaminated resin-rich layer of the GFRP bar increased with increasing compressive strength of concrete. [Copyright &y& Elsevier]