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  • 1
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    Online Resource
    Metabolomic Analysis of Renal Cell Carcinoma in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial
    MDPI AG ; 2022
    In:  Metabolites Vol. 12, No. 12 ( 2022-11-29), p. 1189-
    Details
    In: Metabolites, MDPI AG, Vol. 12, No. 12 ( 2022-11-29), p. 1189-
    Abstract: Background: In the US in 2021, 76,080 kidney cancers are expected and 〉 80% are renal cell carcinomas (RCCs). Along with excess fat, metabolic dysfunction is implicated in RCC etiology. To identify RCC-associated metabolites, we conducted a 1:1 matched case–control study nested within the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial. Methods: We measured 522 serum metabolites in 267 cases/control pairs. Cases were followed for a median 7.1 years from blood draw to diagnosis. Using conditional logistic regression, we computed adjusted odds ratios (ORs) and 95% confidence intervals (CIs) comparing risk between 90th and 10th percentiles of log metabolite intensity, with the significance threshold at a false discovery rate 〈 0.20. Results: Four metabolites were inversely associated with risk of RCC during follow-up—C38:4 PI, C34:0 PC, C14:0 SM, and C16:1 SM (ORs ranging from 0.33–0.44). Two were positively associated with RCC risk—C3-DC-CH3 carnitine and C5 carnitine (ORs = 2.84 and 2.83, respectively). These results were robust when further adjusted for metabolic risk factors (body mass index (BMI), physical activity, diabetes/hypertension history). Metabolites associated with RCC had weak correlations (|r| 〈 0.2) with risk factors of BMI, physical activity, smoking, alcohol, and diabetes/hypertension history. In mutually adjusted models, three metabolites (C38:4 PI, C14:0 SM, and C3-DC-CH3 carnitine) were independently associated with RCC risk. Conclusions: Serum concentrations of six metabolites were associated with RCC risk, and three of these had independent associations from the mutually adjusted model. These metabolites may point toward new biological pathways of relevance to this malignancy.
    Type of Medium: Online Resource
    ISSN: 2218-1989
    URL: Article
    DOI: 10.3390/metabo12121189
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2662251-8
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  • 2
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    NGS Analysis Confirms Common TP53 and RB1 Mutations, and Suggests MYC Amplification in Ocular Adnexal Sebaceous Carcinomas
    MDPI AG ; 2021
    In:  International Journal of Molecular Sciences Vol. 22, No. 16 ( 2021-08-06), p. 8454-
    Details
    In: International Journal of Molecular Sciences, MDPI AG, Vol. 22, No. 16 ( 2021-08-06), p. 8454-
    Abstract: Ocular adnexal (OA) sebaceous carcinomas generally demonstrate more aggressive clinical and histopathological phenotypes than extraocular cases, but the molecular drivers implicated in their oncogenesis remain poorly defined. A retrospective review of surgical and ocular pathology archives identified eleven primary resection specimens of OA sebaceous carcinomas with adequate tissue for molecular analysis; two extraocular cases were also examined. Next-generation sequencing was used to evaluate mutations and copy number changes in a large panel of cancer-associated genes. Fluorescence in situ hybridization (FISH) confirmed MYC copy number gain in select cases, and immunohistochemistry to evaluate MYC protein expression. The commonest mutations occurred in TP53 (10/13) and RB1 (7/13). Additional mutations in clinically actionable genes, or mutations with a frequency of at least 25%, included the NF1 (3/12), PMS2 (4/12), ROS1 (3/12), KMT2C (4/12), MNX1 (6/12), NOTCH1 (4/12), PCLO (3/12), and PTPRT (3/12) loci. Low level copy number gain suggestive of amplification of the MYC locus was seen in two cases, and confirmed using FISH. MYC protein expression, as assessed by immunohistochemistry, was present in almost all sebaceous carcinoma cases. Our findings support the concept that alterations in TP53 and RB1 are the commonest alterations in sebaceous carcinoma, and suggest that MYC may contribute to the oncogenesis of these tumors.
    Type of Medium: Online Resource
    ISSN: 1422-0067
    URL: Article
    DOI: 10.3390/ijms22168454
    Language: English
    Publisher: MDPI AG
    Publication Date: 2021
    detail.hit.zdb_id: 2019364-6
    SSG: 12
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  • 3
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    Fluorescence Methods Applied to the Description of Urea-Dependent YME1L Protease Unfolding
    MDPI AG ; 2020
    In:  Biomolecules Vol. 10, No. 4 ( 2020-04-23), p. 656-
    Details
    In: Biomolecules, MDPI AG, Vol. 10, No. 4 ( 2020-04-23), p. 656-
    Abstract: ATP-dependent proteases are ubiquitous across all kingdoms of life and are critical to the maintenance of intracellular protein quality control. The enzymatic function of these enzymes requires structural stability under conditions that may drive instability and/or loss of function in potential protein substrates. Thus, these molecular machines must demonstrate greater stability than their substrates in order to ensure continued function in essential quality control networks. We report here a role for ATP in the stabilization of the inner membrane YME1L protease. Qualitative fluorescence data derived from protein unfolding experiments with urea reveal non-standard protein unfolding behavior that is dependent on [ATP]. Using multiple fluorophore systems, stopped-flow fluorescence experiments demonstrate a depletion of the native YME1L ensemble by urea-dependent unfolding and formation of a non-native conformation. Additional stopped-flow fluorescence experiments based on nucleotide binding and unfoldase activities predict that unfolding yields significant loss of active YME1L hexamers from the starting ensemble. Taken together, these data clearly define the stress limits of an important mitochondrial protease.
    Type of Medium: Online Resource
    ISSN: 2218-273X
    URL: Article
    DOI: 10.3390/biom10040656
    Language: English
    Publisher: MDPI AG
    Publication Date: 2020
    detail.hit.zdb_id: 2701262-1
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  • 4
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    The Impact of a Dried Fruit and Vegetable Supplement and Fiber Rich Shake on Gut and Health Parameters in Female Healthcare Workers: A Placebo-Controlled, Double-Blind, Randomized Clinical Trial
    MDPI AG ; 2021
    In:  Microorganisms Vol. 9, No. 4 ( 2021-04-14), p. 843-
    Details
    In: Microorganisms, MDPI AG, Vol. 9, No. 4 ( 2021-04-14), p. 843-
    Abstract: Aim: Phytochemicals from fruits and vegetables are known to reduce inflammation and improve overall health. The objective of this study was to determine the effect of a fruit and vegetable concentrate (FVC) and high fiber component on the gut microbiome in an overweight/obese, female population. Methods: The study was a randomized, double blind, placebo-controlled trial with 57 asymptomatic, pre-menopausal, overweight/obese females between 25–50 years of age working in healthcare. Blood and fecal samples were collected before and after two, four and five months of daily supplementation. Metabolic parameters were measured, and the gut microbiome analyzed. Results: No effect was observed with FVC supplementation for blood lipids, glucose and immune parameters. There was an improvement in glucose clearance. The FVC supplement did not result in taxonomic alterations at phyla level, or changes in α or β diversity, but reduced Bacteroides abundance and increased fecal butyrate. An additional high fiber component improved levels of health associated bacteria. Conclusion: The results suggest that a dried fruit and vegetable supplement, with a high fiber meal replacement can alter the intestinal microbiota and improve glucose clearance, suggesting that this combination of supplements can improve glucose metabolism and possibly reduce the risk of insulin resistance.
    Type of Medium: Online Resource
    ISSN: 2076-2607
    URL: Article
    DOI: 10.3390/microorganisms9040843
    Language: English
    Publisher: MDPI AG
    Publication Date: 2021
    detail.hit.zdb_id: 2720891-6
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  • 5
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    One Health Investigation of SARS-CoV-2 Infection and Seropositivity among Pets in Households with Confirmed Human COVID-19 Cases—Utah and Wisconsin, 2020
    MDPI AG ; 2021
    In:  Viruses Vol. 13, No. 9 ( 2021-09-12), p. 1813-
    Details
    In: Viruses, MDPI AG, Vol. 13, No. 9 ( 2021-09-12), p. 1813-
    Abstract: Approximately 67% of U.S. households have pets. Limited data are available on SARS-CoV-2 in pets. We assessed SARS-CoV-2 infection in pets during a COVID-19 household transmission investigation. Pets from households with ≥1 person with laboratory-confirmed COVID-19 were eligible for inclusion from April–May 2020. We enrolled 37 dogs and 19 cats from 34 households. All oropharyngeal, nasal, and rectal swabs tested negative by rRT-PCR; one dog’s fur swabs (2%) tested positive by rRT-PCR at the first sampling. Among 47 pets with serological results, eight (17%) pets (four dogs, four cats) from 6/30 (20%) households had detectable SARS-CoV-2 neutralizing antibodies. In households with a seropositive pet, the proportion of people with laboratory-confirmed COVID-19 was greater (median 79%; range: 40–100%) compared to households with no seropositive pet (median 37%; range: 13–100%) (p = 0.01). Thirty-three pets with serologic results had frequent daily contact (≥1 h) with the index patient before the person’s COVID-19 diagnosis. Of these 33 pets, 14 (42%) had decreased contact with the index patient after diagnosis and none were seropositive; of the 19 (58%) pets with continued contact, four (21%) were seropositive. Seropositive pets likely acquired infection after contact with people with COVID-19. People with COVID-19 should restrict contact with pets and other animals.
    Type of Medium: Online Resource
    ISSN: 1999-4915
    URL: Article
    DOI: 10.3390/v13091813
    Language: English
    Publisher: MDPI AG
    Publication Date: 2021
    detail.hit.zdb_id: 2516098-9
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  • 6
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    Clinical Characteristics and Outcomes of Colorectal Cancer in the ColoCare Study: Differences by Age of Onset
    MDPI AG ; 2021
    In:  Cancers Vol. 13, No. 15 ( 2021-07-29), p. 3817-
    Details
    In: Cancers, MDPI AG, Vol. 13, No. 15 ( 2021-07-29), p. 3817-
    Abstract: Early-onset colorectal cancer has been on the rise in Western populations. Here, we compare patient characteristics between those with early- ( 〈 50 years) vs. late-onset (≥50 years) disease in a large multinational cohort of colorectal cancer patients (n = 2193). We calculated descriptive statistics and assessed associations of clinicodemographic factors with age of onset using mutually-adjusted logistic regression models. Patients were on average 60 years old, with BMI of 29 kg/m2, 52% colon cancers, 21% early-onset, and presented with stage II or III (60%) disease. Early-onset patients presented with more advanced disease (stages III–IV: 63% vs. 51%, respectively), and received more neo and adjuvant treatment compared to late-onset patients, after controlling for stage (odds ratio (OR) (95% confidence interval (CI)) = 2.30 (1.82–3.83) and 2.00 (1.43–2.81), respectively). Early-onset rectal cancer patients across all stages more commonly received neoadjuvant treatment, even when not indicated as the standard of care, e.g., during stage I disease. The odds of early-onset disease were higher among never smokers and lower among overweight patients (1.55 (1.21–1.98) and 0.56 (0.41–0.76), respectively). Patients with early-onset colorectal cancer were more likely to be diagnosed with advanced stage disease, to have received systemic treatments regardless of stage at diagnosis, and were less likely to be ever smokers or overweight.
    Type of Medium: Online Resource
    ISSN: 2072-6694
    URL: Article
    DOI: 10.3390/cancers13153817
    Language: English
    Publisher: MDPI AG
    Publication Date: 2021
    detail.hit.zdb_id: 2527080-1
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  • 7
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    Pregnancy, Birth, Infant, and Early Childhood Neurodevelopmental Outcomes among a Cohort of Women with Symptoms of Zika Virus Disease during Pregnancy in Three Surveillance Sites, Project Vigilancia de Embarazadas con Zika (VEZ), Colombia, 2016–2018
    MDPI AG ; 2021
    In:  Tropical Medicine and Infectious Disease Vol. 6, No. 4 ( 2021-10-12), p. 183-
    Details
    In: Tropical Medicine and Infectious Disease, MDPI AG, Vol. 6, No. 4 ( 2021-10-12), p. 183-
    Abstract: Project Vigilancia de Embarazadas con Zika (VEZ), an intensified surveillance of pregnant women with symptoms of the Zika virus disease (ZVD) in Colombia, aimed to evaluate the relationship between symptoms of ZVD during pregnancy and adverse pregnancy, birth, and infant outcomes and early childhood neurodevelopmental outcomes. During May–November 2016, pregnant women in three Colombian cities who were reported with symptoms of ZVD to the national surveillance system, or with symptoms of ZVD visiting participating clinics, were enrolled in Project VEZ. Data from maternal and pediatric (up to two years of age) medical records were abstracted. Available maternal specimens were tested for the presence of the Zika virus ribonucleic acid and/or anti-Zika virus immunoglobulin antibodies. Of 1213 enrolled pregnant women with symptoms of ZVD, 1180 had a known pregnancy outcome. Results of the Zika virus laboratory testing were available for 569 (48.2%) pregnancies with a known pregnancy outcome though testing timing varied and was often distal to the timing of symptoms; 254 (21.5% of the whole cohort; 44.6% of those with testing results) were confirmed or presumptive positive for the Zika virus infection. Of pregnancies with a known outcome, 50 (4.2%) fetuses/infants had Zika-associated brain or eye defects, which included microcephaly at birth. Early childhood adverse neurodevelopmental outcomes were more common among those with Zika-associated birth defects than among those without and more common among those with laboratory evidence of a Zika virus infection compared with the full cohort. The proportion of fetuses/infants with any Zika-associated brain or eye defect was consistent with the proportion seen in other studies. Enhancements to Colombia’s existing national surveillance enabled the assessment of adverse outcomes associated with ZVD in pregnancy.
    Type of Medium: Online Resource
    ISSN: 2414-6366
    URL: Article
    DOI: 10.3390/tropicalmed6040183
    Language: English
    Publisher: MDPI AG
    Publication Date: 2021
    detail.hit.zdb_id: 2934690-3
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  • 8
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    Recent Crown Thinning in a Boreal Black Spruce Forest Does Not Reduce Spread Rate nor Total Fuel Consumption: Results from an Experimental Crown Fire in Alberta, Canada
    MDPI AG ; 2020
    In:  Fire Vol. 3, No. 3 ( 2020-07-09), p. 28-
    Details
    In: Fire, MDPI AG, Vol. 3, No. 3 ( 2020-07-09), p. 28-
    Abstract: A 3.6 ha experimental fire was conducted in a black spruce peatland forest that had undergone thinning the year prior. After 50 m of spread in a natural stand at 35–60 m min−1, the crown fire (43,000 kW m−1 intensity using Byram’s method) encountered the 50% stem removal treatment; spread rates in the treatment were 50–60 m min−1. Fuel consumption in the control (2.75 kg m−2) was comparable to the treatment (2.35 kg m−2). Proxy measurements of fire intensity using in-stand heat flux sensors as well as photogrammetric flame heights had detected intensity reductions to 30–40% of the control. Crown fuel load reductions (compensated by higher surface fuel load) appear to be the most significant contributor to the decline in intensity, despite drier surface fuels in the treatment. The burn depth of 5 cm in moss and organic soil did not differ between control and treatment. These observations point to the limited effectiveness (likely reductions in crown fire intensity but not spread rate) of stem removal in boreal black spruce fuel types with high stem density, low crown base height and high surface fuel load. The observed fire behaviour impacts differ from drier conifer forests across North America.
    Type of Medium: Online Resource
    ISSN: 2571-6255
    URL: Article
    DOI: 10.3390/fire3030028
    Language: English
    Publisher: MDPI AG
    Publication Date: 2020
    detail.hit.zdb_id: 2924038-4
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  • 9
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    SARS-CoV-2 Infections and Viral Isolations among Serially Tested Cats and Dogs in Households with Infected Owners in Texas, USA
    MDPI AG ; 2021
    In:  Viruses Vol. 13, No. 5 ( 2021-05-19), p. 938-
    Details
    In: Viruses, MDPI AG, Vol. 13, No. 5 ( 2021-05-19), p. 938-
    Abstract: Understanding the ecological and epidemiological roles of pets in the transmission of SARS-CoV-2 is critical for animal and human health, identifying household reservoirs, and predicting the potential enzootic maintenance of the virus. We conducted a longitudinal household transmission study of 76 dogs and cats living with at least one SARS-CoV-2-infected human in Texas and found that 17 pets from 25.6% of 39 households met the national case definition for SARS-CoV-2 infections in animals. This includes three out of seventeen (17.6%) cats and one out of fifty-nine (1.7%) dogs that were positive by RT-PCR and sequencing, with the virus successfully isolated from the respiratory swabs of one cat and one dog. Whole-genome sequences of SARS-CoV-2 obtained from all four PCR-positive animals were unique variants grouping with genomes circulating among people with COVID-19 in Texas. Re-sampling showed persistence of viral RNA for at least 25 d-post initial test. Additionally, seven out of sixteen (43.8%) cats and seven out of fifty-nine (11.9%) dogs harbored SARS-CoV-2 neutralizing antibodies upon initial sampling, with relatively stable or increasing titers over the 2–3 months of follow-up and no evidence of seroreversion. The majority (82.4%) of infected pets were asymptomatic. ‘Reverse zoonotic’ transmission of SARS-CoV-2 from infected people to animals may occur more frequently than recognized.
    Type of Medium: Online Resource
    ISSN: 1999-4915
    URL: Article
    DOI: 10.3390/v13050938
    Language: English
    Publisher: MDPI AG
    Publication Date: 2021
    detail.hit.zdb_id: 2516098-9
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  • 10
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    Dissonance in Young Adult Cigarillo Users’ Categorization of Concept Flavored and Unflavored Products
    MDPI AG ; 2022
    In:  International Journal of Environmental Research and Public Health Vol. 19, No. 12 ( 2022-06-13), p. 7219-
    Details
    In: International Journal of Environmental Research and Public Health, MDPI AG, Vol. 19, No. 12 ( 2022-06-13), p. 7219-
    Abstract: This study asks young adult cigarillo users to categorize their preferred flavor in order to examine user consensus and potential methodological and regulatory implications of flavor name-based categorization systems. Young adult (21–28 years) cigarillo users (n = 426) named and categorized their favorite cigarillo flavor into one of seven categories: Fruit, Sweet and Candy, Mint, Alcohol, Menthol, Tobacco, and Other. Flavor responses were coded as characterizing (ex: Grape, Wine) or concept (ex: Jazz, Diamond) flavors. Variation within and between categories was assessed, including the presence of concept flavors and the placement of flavors in multiple categories. Of the 66 unique flavor names provided, participants placed 20 (30.1%) in more than one flavor category. Most of the Tobacco (76.9%) and Other (69.2%) flavor names appeared in multiple categories. The majority of flavor names in the Tobacco (69.2%) and Other (61.5%) categories were concept flavors. Concept flavors were placed in multiple categories (45.0%) twice as often as characterizing flavors (23.9%). This study has identified dissonance among cigarillo users’ flavor categorizations, particularly for concept flavored and unflavored products. Flavor names may obscure how and whether a product is flavored. Research on and regulation of flavored tobacco products should classify products by flavor additives rather than by name alone.
    Type of Medium: Online Resource
    ISSN: 1660-4601
    URL: Article
    DOI: 10.3390/ijerph19127219
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2175195-X
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