Showing papers by "University of Texas System published in 2018"

Multiplexed Instrument-Free Bar-Chart SpinChip Integrated with Nanoparticle-Mediated Magnetic Aptasensors for Visual Quantitative Detection of Multiple Pathogens.

Abstract: A portable multiplexed bar-chart SpinChip (MB-SpinChip) integrated with nanoparticle-mediated magnetic aptasensors was developed for visual quantitative instrument-free detection of multiple pathogens. This versatile multiplexed SpinChip combines aptamer-specific recognition and nanoparticle-catalyzed pressure amplification to achieve a sample-to-answer output for sensitive point-of-care testing (POCT). This is the first report of pathogen detection using a volumetric bar-chart chip, and it is also the first bar-chart chip using a "spinning" mechanism to achieve multiplexed bar-chart detection. Additionally, the introduction of the spin unit not only enabled convenient sample introduction from one inlet to multiple separate channels in the multiplexed detection, but also elegantly solved the pressure cross-interference problem in the multiplexed volumetric bar-chart chip. This user-friendly MB-SpinChip allows visual quantitative detection of multiple pathogens simultaneously with high sensitivity but without utilizing any specialized instruments. Using this MB-SpinChip, three major foodborne pathogens including Salmonella enterica, Escherichia coli, and Listeria monocytogenes were specifically quantified in apple juice with limits of detection of about 10 CFU/mL. This MB-SpinChip with a bar-chart-based visual quantitative readout has great potential for the rapid simultaneous detection of various pathogens at the point of care and wide applications in food safety, environmental surveillance, and infectious disease diagnosis.

Pharmacological management of cachexia in adult cancer patients: a systematic review of clinical trials

Abstract: Cachexia is a multisystem syndrome characterized by weight loss, anorexia, loss of muscle mass, systemic inflammation, insulin resistance, and functional decline. Management of cachexia involves addressing multiple underlying biological mechanisms. Previous review on pharmacological management of cancer cachexia identified progestins and corticosteroids as effective agents for treatment of cachexia. However, to date no consensus exists on a single effective or standard treatment for management of cachexia. The aim of this systematic review is to determine the effectiveness of pharmacological treatments used to manage cachexia among adult cancer patients. We performed literature searches of PubMed (NLM), Embase (Ovid), and Medline(Ovid) to identify clinical trials focused on pharmacological management of cancer cachexia among adult cancer patients from 2004 to 2018. Three reviewers screened a random selection of abstracts to measure for interrater reliability. After this step, each screener screened two-thirds of all abstracts and 177 studies were identified for full text review. The primary outcome was impact of pharmacological management on change in either weight or lean body mass in cancer patients. We identified 19 articles (representing 20 RCTs) that focused on pharmacological management of cancer cachexia. Agents showing promising results included Anamorelin and Enobosarm. Anamorelin at 50 or 100 mg per day for 12 weeks showed a consistent benefit across all studies and resulted in significant improvement in weight as compared to baseline among cancer patients. Enobosarm at 1 and 3 mg per day was also effective in improving lean body mass and QOL symptoms among advancer stage cancer patients. Finally, use of combination agents provide evidence for targeting multiple pathways underlying cachexia mechanism to achieve maximum benefit. No agents showed functional improvement in cancer patients. Anamorelin as a single agent shows promising results in improving cachexia related weight loss among cancer patients. Further research on combination therapies may be helpful to address critical gaps in cachexia management.

Incompatibility of the circadian protein BMAL1 and HNF4α in hepatocellular carcinoma

Abstract: Hepatocyte nuclear factor 4 alpha (HNF4α) is a master regulator of liver-specific gene expression with potent tumor suppressor activity, yet many liver tumors express HNF4α. This study reveals that P1-HNF4α, the predominant isoform expressed in the adult liver, inhibits expression of tumor promoting genes in a circadian manner. In contrast, an additional isoform of HNF4α, driven by an alternative promoter (P2-HNF4α), is induced in HNF4α-positive human hepatocellular carcinoma (HCC). P2-HNF4α represses the circadian clock gene ARNTL (BMAL1), which is robustly expressed in healthy hepatocytes, and causes nuclear to cytoplasmic re-localization of P1-HNF4α. We reveal mechanisms underlying the incompatibility of BMAL1 and P2-HNF4α in HCC, and demonstrate that forced expression of BMAL1 in HNF4α-positive HCC prevents the growth of tumors in vivo. These data suggest that manipulation of the circadian clock in HNF4α-positive HCC could be a tractable strategy to inhibit tumor growth and progression in the liver.

Exploring Applications of Radiomics in Magnetic Resonance Imaging of Head and Neck Cancer: A Systematic Review.

Abstract: Background: Radiomics has been widely investigated for non-invasive acquisition of quantita-tive textural information from anatomic structures. While the vast majority of radiomic analysis is performed on images obtained from computed tomography (CT), magnetic resonance imaging (MRI)-based radiomics has generated increased attention. In head and neck cancer (HNC), how-ever, attempts to perform consistent investigations are sparse, and it is unclear whether the result-ing textural features can be reproduced. To address this unmet need, we systematically reviewed the quality of existing MRI radiomics research in HNC. Methods: Literature search was conducted in accordance with guidelines established by Pre-ferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). Electronic data-bases were examined from January 1990 through November 2017 for common radiomic key-words. Eligible completed studies were then scored using a standardized checklist that we de-veloped from Enhancing the Quality and Transparency of Health Research (EQUATOR) guide-lines for reporting machine learning predictive model specifications and results in biomedical re-search, defined by Luo et al.(1). Descriptive statistics of checklist scores were populated, and a sub-group analysis of methodology items alone was conducted in comparison to overall scores. Results: Sixteen completed studies and four ongoing trials were selected for inclusion. Of the completed studies, the nasopharynx was the most common site of study (27.5%).MRI modalities varied with only four of the completed studies (25%) extracting radiomic features from a single sequence. Study sample sizes ranged between 13-118 patients (median of 20), and final radiomic signatures ranged from 2-279 features. Analyzed end-points included either segmentation or his-topathological classification parameters (44%) or prognostic and predictive biomarkers (56%) . Liu et al.(39) addressed the highest number of our checklist items (Total Score [TS]: 48), and a sub-group analysis of methodology checklist items alone did not demonstrate any difference in scoring trends between studies (Spearman’s ρ = 0.94 [p <.0001]). Conclusions: Although MRI radiomic applications demonstrate predictive potential in analyzing diverse HNC outcomes, methodological variances preclude accurate and collective interpretation of data.

Wait of a Decade: Did SPEC CPU 2017 Broaden the Performance Horizon?

Abstract: The recently released SPEC CPU2017 benchmark suite has already started receiving a lot of attention from both industry and academic communities. However, due to the significantly high size and complexity of the benchmarks, simulating all the CPU2017 benchmarks for design trade-off evaluation is likely to become extremely difficult. Simulating a randomly selected subset, or a random input set, may result in misleading conclusions. This paper analyzes the SPEC CPU2017 benchmarks using performance counter based experimentation from seven commercial systems, and uses statistical techniques such as principal component analysis and clustering to identify similarities among benchmarks. Such analysis can reveal benchmark redundancies and identify subsets for researchers who cannot use all benchmarks in pre-silicon design trade-off evaluations. Many of the SPEC CPU2006 benchmarks have been replaced with larger and complex workloads in the SPEC CPU2017 suite. However, compared to CPU2006, it is unknown whether SPEC CPU2017 benchmarks have different performance demands or whether they stress machines differently. Additionally, to evaluate the balance of CPU2017 benchmarks, we analyze the performance characteristics of CPU2017 workloads and compare them with emerging database, graph analytics and electronic design automation (EDA) workloads. This paper provides the first detailed analysis of SPEC CPU2017 benchmark suite for the architecture community.

TMEM9 promotes intestinal tumorigenesis through vacuolar-ATPase-activated Wnt/β-catenin signalling

Abstract: Vesicular acidification and trafficking are associated with various cellular processes. However, their pathologic relevance to cancer remains elusive. We identified transmembrane protein 9 (TMEM9) as a vesicular acidification regulator. TMEM9 is highly upregulated in colorectal cancer. Proteomic and biochemical analyses show that TMEM9 binds to and facilitates assembly of vacuolar-ATPase (v-ATPase), a vacuolar proton pump, resulting in enhanced vesicular acidification and trafficking. TMEM9-v-ATPase hyperactivates Wnt/β-catenin signalling via lysosomal degradation of adenomatous polyposis coli (APC). Moreover, TMEM9 transactivated by β-catenin functions as a positive feedback regulator of Wnt signalling in colorectal cancer. Genetic ablation of TMEM9 inhibits colorectal cancer cell proliferation in vitro, ex vivo and in vivo mouse models. Moreover, administration of v-ATPase inhibitors suppresses intestinal tumorigenesis of APC mouse models and human patient-derived xenografts. Our results reveal the unexpected roles of TMEM9-controlled vesicular acidification in hyperactivating Wnt/β-catenin signalling through APC degradation, and propose the blockade of TMEM9-v-ATPase as a viable option for colorectal cancer treatment.

Measurement of elastin, collagen, and total protein levels in tissues.

Abstract: Elastin and collagen levels in tissues are frequently difficult to measure because of each protein's limited solubility. This chapter provides detailed methodology for the determination of elastin, collagen, and total protein levels in a single tissue sample. All three assays start with an acid hydrolysate of the tissue, which breaks the tissue-associated proteins down to their component amino acids. Marker amino acids unique to each protein (desmosine for elastin and hydroxyproline for collagen) are then quantified. Total protein content, useful as a denominator for data normalization, can also be measured from a portion of the hydrolysate using an assay for free amino groups. These measurements are performed using convenient 96-well assay plates and require only a plate reader to determine absorbance.

Microsoft Dialogue Challenge: Building End-to-End Task-Completion Dialogue Systems

Abstract: This proposal introduces a Dialogue Challenge for building end-to-end task-completion dialogue systems, with the goal of encouraging the dialogue research community to collaborate and benchmark on standard datasets and unified experimental environment. In this special session, we will release human-annotated conversational data in three domains (movie-ticket booking, restaurant reservation, and taxi booking), as well as an experiment platform with built-in simulators in each domain, for training and evaluation purposes. The final submitted systems will be evaluated both in simulated setting and by human judges.

Microsoft Dialogue Challenge: Building End-to-End Task-Completion Dialogue Systems.

Abstract: This proposal introduces a Dialogue Challenge for building end-to-end task-completion dialogue systems, with the goal of encouraging the dialogue research community to collaborate and benchmark on standard datasets and unified experimental environment. In this special session, we will release human-annotated conversational data in three domains (movie-ticket booking, restaurant reservation, and taxi booking), as well as an experiment platform with built-in simulators in each domain, for training and evaluation purposes. The final submitted systems will be evaluated both in simulated setting and by human judges.

Determining the effects of tillage and nitrogen sources on soil N2O emission.

Abstract: Soil tillage and fertilization can affect the abundance of nitrifying and denitrifying microbial communities known to regulate N 2 O losses from agricultural soils. We assessed the effects of mineral and organic N sources on short-term N 2 O emissions from a Rhodic Nitisol under contrasting soil disturbance. The experiment followed a split-plot design with two soil tillage systems as main plots (tilled soil: TS, and no-till soil: NTS) and five fertilization treatments as subplots, where 140 kg N ha −1 were applied either as urea (UR), raw swine slurry (RS), anaerobically digested swine slurry (ADS), or composted swine slurry (CS). A treatment without N fertilization was used as control (CTR). N 2 O emissions were determined by using static chambers and correlated with soil (0–0.1 m) temperature, water-filled pore space (WFPS), dissolved organic carbon (DOC), ammonium (NH 4 + -N), nitrate (NO 3 − -N) and the abundance of specific nitrification and denitrification biomarker genes [ammonium monooxygenase ( amoA ), nitrate- ( narG ), nitrite- ( nirS ), nitric oxide- ( qnorB ) and nitrous oxide reductases ( nosZ )]. Denitrification was the main source of N 2 O as assessed by increased narG/16S rDNA and narG/nosZ ratios regardless of soil tillage. N 2 O emissions were augmented in the NTS (30 to 200% higher than TS) where higher soil WFPS (0.6-0.7 cm 3 cm −3 ) favored incomplete denitrification. The application of ADS in the NTS decreased denitrification rates and cumulative N 2 O emission by 47% in comparison with RS (2.9 and 5.6 kg N 2 O-N ha −1 , respectively). Interestingly, N 2 O emission from the NTS receiving CS (4.7 kg N 2 O-N ha −1 ) was also promoted by the proliferation of heterotrophic nitrifying bacteria communities. Overal, swine slurry treatment can help mitigate N 2 O emission from agricultural soils, particularly in regions where this source of fertilizer is abundant and readily available.

MtrA Response Regulator Controls Cell Division and Cell Wall Metabolism and Affects Susceptibility of Mycobacteria to the First Line Antituberculosis Drugs

Abstract: The biological processes regulated by the essential response regulator MtrA and the growth conditions promoting its activation in Mycobacterium tuberculosis, a slow grower and pathogen, are largely unknown. Here, using a gain-of-function mutant, MtrAY 102C, which functions in the absence of the cognate MtrB sensor kinase, we show that the MtrA regulon includes several genes involved in the processes of cell division and cell wall metabolism. The expression of selected MtrA targets and intracellular MtrA levels were compromised under replication arrest induced by genetic manipulation and under stress conditions caused by toxic radicals. The loss of the mtrA gene in M. smegmatis, a rapid grower and non-pathogen, produced filamentous cells with branches and bulges, indicating defects in cell division and cell shape. The ΔmtrA mutant was sensitized to rifampicin and vancomycin and became more resistant to isoniazid, the first line antituberculosis drug. Our data are consistent with the proposal that MtrA controls the optimal cell division, cell wall integrity, and susceptibility to some antimycobacterial drugs.

Genome-wide association meta-analysis of circulating odd-numbered chain saturated fatty acids: Results from the CHARGE Consortium.

Abstract: Background Odd-numbered chain saturated fatty acids (OCSFA) have been associated with potential health benefits. Although some OCSFA (e.g., C15:0 and C17:0) are found in meats and dairy products, sources and metabolism of C19:0 and C23:0 are relatively unknown, and the influence of non-dietary determinants, including genetic factors, on circulating levels of OCSFA is not established. Objective To elucidate the biological processes that influence circulating levels of OCSFA by investigating associations between genetic variation and OCSFA. Design We performed a meta-analysis of genome-wide association studies (GWAS) of plasma phospholipid/erythrocyte levels of C15:0, C17:0, C19:0, and C23:0 among 11,494 individuals of European descent. We also investigated relationships between specific single nucleotide polymorphisms (SNPs) in the lactase (LCT) gene, associated with adult-onset lactase intolerance, with circulating levels of dairy-derived OCSFA, and evaluated associations of candidate sphingolipid genes with C23:0 levels. Results We found no genome-wide significant evidence that common genetic variation is associated with circulating levels of C15:0 or C23:0. In two cohorts with available data, we identified one intronic SNP (rs13361131) in myosin X gene (MYO10) associated with C17:0 level (P = 1.37×10−8), and two intronic SNP (rs12874278 and rs17363566) in deleted in lymphocytic leukemia 1 (DLEU1) region associated with C19:0 level (P = 7.07×10−9). In contrast, when using a candidate-gene approach, we found evidence that three SNPs in LCT (rs11884924, rs16832067, and rs3816088) are associated with circulating C17:0 level (adjusted P = 4×10−2). In addition, nine SNPs in the ceramide synthase 4 (CERS4) region were associated with circulating C23:0 levels (adjusted P<5×10−2). Conclusions Our findings suggest that circulating levels of OCSFA may be predominantly influenced by non-genetic factors. SNPs associated with C17:0 level in the LCT gene may reflect genetic influence in dairy consumption or in metabolism of dairy foods. SNPs associated with C23:0 may reflect a role of genetic factors in the synthesis of sphingomyelin.

Deregulation of CRAD-controlled cytoskeleton initiates mucinous colorectal cancer via β-catenin

Abstract: Epithelial integrity is maintained by the cytoskeleton and through cell adhesion. However, it is not yet known how a deregulated cytoskeleton is associated with cancer. We identified cancer-related regulator of actin dynamics (CRAD) as frequently mutated or transcriptionally downregulated in colorectal cancer. We found that CRAD stabilizes the cadherin–catenin–actin complex via capping protein inhibition. The loss of CRAD inhibits F-actin polymerization and subsequently disrupts the cadherin–catenin–actin complex, which leads to β-catenin release and Wnt signalling hyperactivation. In mice, CRAD knockout induces epithelial cell integrity loss and Wnt signalling activation, resulting in the development of intestinal mucinous adenoma. With APC mutation, CRAD knockout initiates and accelerates mucinous and invasive adenoma development in the colorectum. These results define CRAD as a tumour suppressor, the inactivation of which deregulates the cytoskeleton and hyperactivates Wnt signalling thus initiating mucinous colorectal cancer. Our study reveals the unexpected roles of an actin cytoskeletal regulator in maintaining epithelial cell integrity and suppressing tumorigenesis. Jung et al. demonstrate that loss of CRAD impairs F-actin polymerization and disrupts the cadherin–catenin–actin complex, thereby hyperactivating Wnt signalling and promoting mucinous intestinal tumorigenesis.

Unique Contribution of Haptoglobin and Haptoglobin Genotype in Aneurysmal Subarachnoid Hemorrhage.

Abstract: Survivors of cerebral aneurysm rupture are at risk for significant morbidity and neurological deficits. Much of this is related to the effects of blood in the subarachnoid space which induces an inflammatory cascade with numerous downstream consequences. Recent clinical trials have not been able to reduce the toxic effects of free hemoglobin or improve clinical outcome. One reason for this may be the inability to identify patients at high risk for neurologic decline. Recently, haptoglobin genotype has been identified as a pertinent factor in diabetes, sickle cell, and cardiovascular disease, with the Hp 2-2 genotype contributing to increased complications. Haptoglobin is a protein synthesized by the liver that binds free hemoglobin following red blood cell lysis, and in doing so, prevents hemoglobin induced toxicity and facilitates clearance. Clinical studies in patients with subarachnoid hemorrhage indicate that Hp 2-2 patients may be a high-risk group for hemorrhage related complications and poor outcome. We review the relevance of haptoglobin in subarachnoid hemorrhage and discuss the effects of genotype and expression levels on the known mechanisms of early brain injury (EBI) and cerebral ischemia after aneurysm rupture. A better understanding of haptoglobin and its role in preventing hemoglobin related toxicity should lead to novel therapeutic avenues.

A phase II clinical study to assess the feasibility of self and partner anal examinations to detect anal canal abnormalities including anal cancer

Abstract: Objective Anal cancer is a common cancer among men who have sex with men (MSM); however, there is no standard screening protocol for anal cancer. We conducted a phase II clinical trial to assess the feasibility of teaching MSM to recognise palpable masses in the anal canal which is a common sign of anal cancer in men. Methods A clinician skilled in performing digital anorectal examinations (DARE) used a pelvic manikin to train 200 MSM, aged 27–78 years, how to do a self-anal examination (SAE) for singles or a partner anal examination (PAE) for couples. The clinician then performed a DARE without immediately disclosing results, after which the man or couple performed an SAE or PAE, respectively. Percentage agreement with the clinician DARE in addition to sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) were calculated for the SAE, PAE and overall. Results Men had a median age of 52 years, 42.5% were African American and 60.5% were HIV positive. DARE detected abnormalities in 12 men while the men’s SAE/PAEs detected 9 of these. A total of 93.0% of men classified the health of their anal canal correctly (95% CI 89.5 to 96.5). Overall percentage agreement, sensitivity and specificity were 93.0%, 75.0% and 94.2%, respectively, while PPV and NPV were 45.0% and 98.3%, respectively. The six men who detected the abnormality had nodules/masses ≥3 mm in size. More than half of men (60.5%) reported never checking their anus for an abnormality; however, after performing an SAE/PAE, 93.0% said they would repeat it in the future. Conclusion These results suggest that tumours of ≥3 mm may be detectable by self or partner palpation among MSM and encourage further investigation given literature suggesting a high cure rate for anal cancer tumours ≤10 mm.

Genetic determinants of cortical structure (thickness, surface area and volumes) among disease free adults in the CHARGE Consortium

Abstract: Cortical thickness, surface area and volumes (MRI cortical measures) vary with age and cognitive function, and in neurological and psychiatric diseases We examined heritability, genetic correlations and genome-wide associations of cortical measures across the whole cortex, and in 34 anatomically predefined regions Our discovery sample comprised 22,822 individuals from 20 cohorts within the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) consortium and the United Kingdom Biobank Significant associations were replicated in the Enhancing Neuroimaging Genetics through Meta-analysis (ENIGMA) consortium, and their biological implications explored using bioinformatic annotation and pathway analyses We identified genetic heterogeneity between cortical measures and brain regions, and 161 genome-wide significant associations pointing to wnt/β-catenin, TGF-β and sonic hedgehog pathways There was enrichment for genes involved in anthropometric traits, hindbrain development, vascular and neurodegenerative disease and psychiatric conditions These data are a rich resource for studies of the biological mechanisms behind cortical development and aging

Structural and functional characterization of protein-lipid interactions of the Salmonella typhimurium melibiose transporter MelB.

Abstract: Membrane lipids play critical roles in the structure and function of membrane-embedded transporters. Salmonella typhimurium MelB (MelBSt) is a symporter coupling melibiose translocation with a cation (Na+, Li+, or H+). We present an extensive study on the effects of specific phospholipids on the structure of MelBSt and the melibiose transport catalyzed by this protein. Lipidomic analysis and thin-layer chromatography (TLC) experiments reveal that at least one phosphatidylethanolamine (PE) and one phosphatidylglycerol (PG) molecule associate with MelBSt at high affinities. Solid-state nuclear magnetic resonance (ssNMR) spectroscopy experiments confirmed the presence of lipid tails and glycerol backbones that co-purified with MelBSt; headgroups of PG were also observed. Studies with lipid-engineered strains, including PE-deficient, cardiolipin (CL)- and PG-deficient, or CL-deficient strains, show that lack of PE or PG, however not CL, largely inhibits both H+- and Na+-coupled melibiose active transport to different extents. Interestingly, neither the co-substrate binding (melibiose or Na+) nor MelBSt folding and stability are affected by changing lipid compositions. Remarkably, the delipidated MelBSt with only 2–3 bound lipids, regardless of the headgroup species, also exhibits unchanged melting temperature values as shown by circular dichroism spectroscopy. (1) Lipid tails and glycerol backbones of interacting PE and PG may contribute to the stability of the structure of MelBSt. (2) The headgroups of PE and PG, but not of CL, play important roles in melibiose transport; however, lipid headgroups do not modulate the folding and stability of MelBSt.

Decreased interhemispheric coordination in the posterior default-mode network and visual regions as trait alterations in first-episode, drug-naive major depressive disorder.

Abstract: Decreased homotopic connectivity has been implicated in the neurophysiology of major depressive disorder (MDD) with inconsistent findings. A combination of clinical and methodological variabilities may account for the inconsistency, and thus limiting the reproducibility of the findings. The present study aims to examine voxel-mirrored homotopic connectivity (VMHC) alterations in two independent samples of patients with first-episode, drug-naive MDD. The samples included 59 patients and 31 controls from Sample 1 and 29 patients and 24 controls from Sample 2. VMHC was evaluated in both samples with an overlapping technique, which was used to define regions of abnormality common to both samples. Moreover, receiver operating characteristic curve and support vector machine were employed to differentiate the patients from the controls in both samples. Compared with the controls, the patients in both samples exhibited decreased VMHC in overlapped brain clusters, including the posterior cingulate cortex (PCC) and cuneus. Moreover, the VMHC values in the PCC and cuneus and a combination of the VMHC values in these two clusters could robustly discriminate between patients and controls with good sensitivities and specificities in both samples. This study is the first to examine VMHC abnormalities in first-episode, drug-naive patients with MDD in two independent samples by using an overlapped technique. The patients exhibit decreased VMHC in overlapping clusters in the posterior default-mode network and visual regions, which may be trait alterations for MDD. The present study provides a new perspective for understanding the neurophysiologic abnormalities of VMHC in MDD.

Transit use and physical activity: Findings from the Houston travel-related activity in neighborhoods (TRAIN) study.

Abstract: Transportation-related physical activity can significantly increase daily total physical activity through active transportation or walking/biking to transit stops. The purpose of this study was to assess the relations between transit-use and self-reported and monitor-based physical activity levels in a predominantly minority population from the Houston Travel-Related Activity in Neighborhoods (TRAIN) Study. This was a cross-sectional analysis of 865 adults living in Houston, Texas between 2013 and 2015. The exposure variable was transit-use (non-users, occasional users, and primary users). Self-reported and accelerometer-determined physical activity were the outcomes of interest. Regression models adjusting for age, sex, race/ethnicity, and other covariates of interest were built to test the hypothesis that transit user status was directly associated with 1) minutes of moderate-intensity physical activity and 2) the prevalence of achieving the physical activity guidelines. The majority of participants were female, non-Hispanic black, and almost one-third had a high school education or less. After adjustment, primary transit-use was associated with 134.2 (p

Comparison of Phenotypic and Functional Characteristics Between Canine Non-B, Non-T Natural Killer Lymphocytes and CD3+CD5dimCD21- Cytotoxic Large Granular Lymphocytes.

Abstract: Natural killer (NK) cells play a pivotal role in the immune response against infections and malignant transformation, and adopted transfer of NK cells is thought to be a promising therapeutic approach for cancer patients. Previous reports describing the phenotypic features of canine NK cells have produced inconsistent results. Canine NK cells are still defined as non-B and non-T (CD3-CD21-) large granular lymphocytes. However, a few reports have demonstrated that canine NK cells share the phenotypic characteristics of T lymphocytes, and that CD3+CD5dimCD21- lymphocytes are putative canine NK cells. Based on our previous reports, we hypothesized that phenotypic modulation could occur between these two populations during activation. In this study, we investigated the phenotypic and functional differences between CD3+CD5dimCD21- (cytotoxic large granular lymphocytes) and CD3-CD5-CD21- NK lymphocytes before and after culture of peripheral blood mononuclear cells isolated from normal dogs. The results of this study show that CD3+CD5dimCD21- lymphocytes can be differentiated into non-B, non-T NK (CD3-CD5-CD21-TCRαβ-TCRγδ-GranzymeB+) lymphocytes through phenotypic modulation in response to cytokine stimulation. In vitro studies of purified CD3+CD5dimCD21- cells showed that CD3-CD5-CD21- cells are derived from CD3+CD5dimCD21- cells through phenotypic modulation. CD3+CD5dimCD21- cells share more NK cell functional characteristics compared with CD3-CD5-CD21- cells, including the expression of T-box transcription factors (Eomes, T-bet), the production of granzyme B and interferon-γ, and the expression of NK cell-related molecular receptors such as NKG2D and NKp30. In conclusion, the results of this study suggest that CD3+CD5dimCD21- and CD3-CD5-CD21- cells both contain a subset of putative NK cells, and the difference between the two populations may be due to the degree of maturation.

Using mobile technology to increase safety awareness among dairy workers in the United States.

Abstract: Background: Modern US dairy farm operations present multiple safety hazards which may result in worker injuries, illnesses and fatalities The US industry trend towards large-herd milking opera

Management of Immune-mediated Cytopenias in the Era of Cancer Immunotherapy: A Report of 4 Cases.

Abstract: Recent advancements in immunotherapy have brought promising drugs to fight cancers; a subset of immunotherapy medications are known as checkpoint inhibitors. Their mechanism of action relies on upregulating antitumor response by reversing T-cell suppression; as a consequence the effect can also result in a spectrum of immune related complications. Reported complications to date include: skin, gastrointestinal mucosa, hypophysis, liver, endocrine system, nervous system, kidney, musculoskeletal system and the hematologic system. The management of immune related complications typically includes the use of steroids and other strategies of immunosuppression. The current recommendations are not organ-specific and little is known about the response and outcomes related to the hematologic system. Hereby we report four cases evaluated at the hematology service at the University of Texas MD Anderson Cancer Center for cytopenias after check point inhibitor therapies. All cases were responsive to conventional interventions for immune-mediated cytopenias.

Forensic Nursing State of the Science: Research and Practice Opportunities.

Abstract: Introduction The International Association of Forensic Nurses (IAFN) is the only nursing organization advancing the forensic nursing specialty. The organization seeks to advance the profession, and one mechanism for doing so is development of a research agenda. Methods The purpose of this action-based research study was to aid in the development of a forensic nursing research agenda. The study was carried out in two integral stages: (a) focus groups with IAFN members attending the annual conference and (b) reviewing posted IAFN member listserv material. Results The findings of this study identified similar gaps of other nursing specialties experiencing "growing pains," including role confusion and variation in educational preparation. Conclusion Findings from this study will inform development of the IAFN 5-year research agenda to advance forensic nursing science and evidence-based practice.

Cryo-EM Reveals Ligand Induced Allostery Underlying InsP3R Channel Gating

Abstract: Inositol-1,4,5-trisphosphate receptors (InsP 3 Rs) are cation channels that mobilize Ca 2+ from intracellular stores in response to a wide range of cellular stimuli. The paradigm of InsP 3 R activation is the coupled interplay between binding of InsP 3 and Ca 2+ that switches the ion conduction pathway between closed and open states to enable the passage of Ca 2+ through the channel. However, the molecular mechanism of how the receptor senses and decodes ligand-binding signals into gating motion remains unknown. Here we present the electron cryo-microscopy structure of InsP 3 R1 from rat cerebellum determined to 4.1 A resolution in the presence of activating concentrations of Ca 2+ and adenophostin A (AdA), a structural mimetic of InsP 3 and the most potent known agonist of the channel. Comparison with the 3.9 A-resolution structure of InsP 3 R1 in the Apo-state, also reported herein, reveals the binding arrangement of AdA in the tetrameric channel assembly and striking ligand-induced conformational rearrangements within cytoplasmic domains coupled to the dilation of a hydrophobic constriction at the gate. Together, our results provide critical insights into the mechanistic principles by which ligand-binding allosterically gates InsP 3 R channel.