Publications by authors named "Jason Williams"

398 Publications

BOSC 2021, the 22nd Annual Bioinformatics Open Source Conference.

F1000Res 2021 18;10. Epub 2021 Oct 18.

Cold Spring Harbor Laboratory, Cold Spring Harbor, NY, 11724, USA.

The 22nd annual Bioinformatics Open Source Conference (BOSC 2021, open-bio.org/events/bosc-2021/) was held online as a track of the 2021 Intelligent Systems for Molecular Biology / European Conference on Computational Biology (ISMB/ECCB) conference. Launched in 2000 and held every year since, BOSC is the premier meeting covering topics related to open source software and open science in bioinformatics. In 2020, BOSC partnered with the Galaxy Community Conference to form the Bioinformatics Community Conference (BCC2020); that was the first BOSC to be held online. This year, BOSC returned to its roots as part of ISMB/ECCB 2021. As in 2020, the Covid-19 pandemic made it impossible to hold the conference in person, so ISMB/ECCB 2021 took place as an online meeting attended by over 2000 people from 79 countries. Nearly 200 people participated in BOSC sessions, which included 27 talks reviewed and selected from submitted abstracts, and three invited keynote talks representing a range of global perspectives on the role of open science and open source in driving research and inclusivity in the biosciences, one of which was presented in French with English subtitles.
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http://dx.doi.org/10.12688/f1000research.74074.1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8524300PMC
November 2021

Society for Cardiovascular Magnetic Resonance 2020 Case of the Week series.

J Cardiovasc Magn Reson 2021 10 11;23(1):108. Epub 2021 Oct 11.

Division of Cardiology, University of Iowa Hospitals and Clinic, Iowa City, Iowa, USA.

The Society for Cardiovascular Magnetic Resonance (SCMR) is an international society focused on the research, education, and clinical application of cardiovascular magnetic resonance (CMR). Case of the week is a case series hosted on the SCMR website ( https://www.scmr.org ) that demonstrates the utility and importance of CMR in the clinical diagnosis and management of cardiovascular disease. Each case consists of the clinical presentation and a discussion of the condition and the role of CMR in diagnosis and guiding clinical management. The cases are all instructive and helpful in the approach to patient management. We present a digital archive of the 2020 Case of the Week series of 11 cases as a means of further enhancing the education of those interested in CMR and as a means of more readily identifying these cases using a PubMed or similar search engine.
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http://dx.doi.org/10.1186/s12968-021-00799-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8504030PMC
October 2021

Gender Differences in Descriptive Norms as Mediators of a Military Web-Based Alcohol Intervention.

Authors:
Jason Williams

J Stud Alcohol Drugs 2021 09;82(5):659-667

Center for Behavioral Health Epidemiology, Implementation, and Evaluation Research, RTI International, Research Triangle Park, North Carolina.

Objective: Personalized normative feedback, in which a respondent's perceived norms are contrasted with more accurate estimates of alcohol use, has been found to be an effective component in brief alcohol interventions. Less certain is how the impact of feedback as a mediator of behavior change may depend on, or be moderated by, gender. This study examined differences in mediation through two descriptive norms--the number of drinks consumed per occasion and frequency of drinking occasions--using data from the evaluation of a military web-based alcohol intervention.

Method: Gender differences in mediation of the Drinker's Check-Up's effects through descriptive norms were examined with multiple group path models and were tested with Wald and bootstrap confidence intervals for significance.

Results: Results varied by the type of descriptive norm. Mediation by perceived norms about the number of drinks peers consumed did not vary significantly by gender. In contrast, mediated effects through norms about how often peers drank differed significantly by gender for the number of days alcohol was consumed, the number of binge episodes, heavy drinker status, and the number of drinks consumed per drinking episode. Female military personnel showed a greater number of mediated effects through norms about drinking frequency than did males.

Conclusions: Differences in mediation depend on the type of descriptive norm acting as mediator as well as the type of alcohol use outcome. Further research on these differences may enable tailoring of interventions to maximize the effectiveness of norms as agents of alcohol use change.
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September 2021

Building an assessment of community-defined social-emotional competencies from the ground up in Tanzania.

Child Dev 2021 Nov 13;92(6):e1095-e1109. Epub 2021 Sep 13.

University of Georgia, Athens, Georgia, USA.

Two studies were conducted in 2017 to investigate children's competencies seen as important by communities in Mtwara, Tanzania. Qualitative data from 95 parents (34 women) and 27 teachers (11 women) in Study 1 indicated that dimensions of social responsibility, such as obedience, were valued highly. In Study 2, the competencies of 477 children (245 girls), aged 4-13 years, were rated by teachers and parents. Factor analysis found the obedient factor explained the most variance in parent rating. In line with predictions, urban residence, parental socioeconomic status (SES), and parental education were all positively associated with ratings of curiosity, and parental SES was negatively associated with obedience and emotional regulation. Findings illustrate the need for culturally specific frameworks of social-emotional learning.
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http://dx.doi.org/10.1111/cdev.13673DOI Listing
November 2021

The impact of community-level prevention strategies on high-dose opioid dispensing rates: 2014-2019.

Drug Alcohol Depend 2021 10 27;227:108988. Epub 2021 Aug 27.

RTI International, Research Triangle Park, NC, USA.

Background: Prescription opioids played a major role in the current opioid overdose epidemic. High rates of opioid prescribing and dispensing exposed many people to opioids, and high-dose opioid prescriptions (e.g., 90 morphine milligram equivalents [MME] per day) contributed to increases in opioid overdoses. The Centers for Disease Control and Prevention (CDC) Prevention for States (PfS) program provided funding to jurisdictions ("PfS recipients") with a high burden of opioid-involved overdoses. This paper examines associations between strategies addressing high-dose opioid prescribing and changes in high-dose opioid dispensing.

Methods: Monthly opioid dispensing data (2014-2019) from IQVIA Xponent were analyzed using longitudinal growth models (LGM) to compare high-dose opioid dispensing rates in the 29 jurisdictions that participated in PfS with rates in non-PfS jurisdictions. Additional models examined associations between specific PfS activities and changes in high-dose dispensing among PfS recipients.

Results: High-dose dispensing rates decreased significantly in both PfS and non-PfS jurisdictions from 2014 to 2019. Rates of high-dose opioid dispensing rates in PfS jurisdictions were not significantly different than those in non-PfS jurisdictions (p = 0.07). Among PfS recipients, multiple activities were associated with decreases in high-dose dispensing rates over time, including moving towards real-time prescription drug monitoring program (PDMP) reporting (p < 0.001) and implementation of opioid dispensing interventions for insurers/ health systems (p < 0.05).

Conclusions: High-dose opioid dispensing rates decreased throughout the United States from 2014-2019. As the drug epidemic continues to evolve, implementation of prevention activities by state and local partners is important. These findings highlight two potential prevention strategies and activities that jurisdictions can utilize.
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http://dx.doi.org/10.1016/j.drugalcdep.2021.108988DOI Listing
October 2021

Berotralstat (BCX7353): Structure-Guided Design of a Potent, Selective, and Oral Plasma Kallikrein Inhibitor to Prevent Attacks of Hereditary Angioedema (HAE).

J Med Chem 2021 09 26;64(17):12453-12468. Epub 2021 Aug 26.

Hereditary angioedema (HAE) is a rare and potentially life-threatening disease that affects an estimated 1 in 50 000 individuals worldwide. Until recently, prophylactic HAE treatment options were limited to injectables, a burdensome administration route that has driven the need for an oral treatment. A substantial body of evidence has shown that potent and selective plasma kallikrein inhibitors that block the generation of bradykinin represent a promising approach for the treatment of HAE. Berotralstat (BCX7353, discovered by BioCryst Pharmaceuticals using a structure-guided drug design strategy) is a synthetic plasma kallikrein inhibitor that is potent and highly selective over other structurally related serine proteases. This once-daily, small-molecule drug is the first orally bioavailable prophylactic treatment for HAE attacks, having successfully completed a Phase III clinical trial (meeting its primary end point) and recently receiving the U.S. Food and Drug Administration's approval for the prophylactic treatment of HAE attacks in patients 12 years and older.
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http://dx.doi.org/10.1021/acs.jmedchem.1c00511DOI Listing
September 2021

Characterization of SARS2 Nsp15 nuclease activity reveals it's mad about U.

Nucleic Acids Res 2021 Sep;49(17):10136-10149

Signal Transduction Laboratory, National Institute of Environmental Health Sciences, National Institutes of Health, Department of Health and Human Services, 111 T. W. Alexander Drive, Research Triangle Park, NC 27709, USA.

Nsp15 is a uridine specific endoribonuclease that coronaviruses employ to cleave viral RNA and evade host immune defense systems. Previous structures of Nsp15 from across Coronaviridae revealed that Nsp15 assembles into a homo-hexamer and has a conserved active site similar to RNase A. Beyond a preference for cleaving RNA 3' of uridines, it is unknown if Nsp15 has any additional substrate preferences. Here, we used cryo-EM to capture structures of Nsp15 bound to RNA in pre- and post-cleavage states. The structures along with molecular dynamics and biochemical assays revealed critical residues involved in substrate specificity, nuclease activity, and oligomerization. Moreover, we determined how the sequence of the RNA substrate dictates cleavage and found that outside of polyU tracts, Nsp15 has a strong preference for purines 3' of the cleaved uridine. This work advances our understanding of how Nsp15 recognizes and processes viral RNA, and will aid in the development of new anti-viral therapeutics.
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http://dx.doi.org/10.1093/nar/gkab719DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8385992PMC
September 2021

Coronary artery ectasia in post-pericardiotomy syndrome.

Echocardiography 2021 Aug 6. Epub 2021 Aug 6.

The Heart Center, Nationwide Children's Hospital, 700 Children's Drive, Columbus, Ohio, USA.

Post-pericardiotomy syndrome (PPS) is a common inflammatory process following cardiac surgery, in which the pericardial space was opened. Pericardial effusion (PE) is a common manifestation in PPS; however, coronary artery dilation is not associated with PPS. Inflammatory vasculitis in children are known to cause coronary dilation, in conditions such as in Kawasaki Disease (KD). We report a patient with PPS and concomitant coronary dilation by transthoracic echocardiography (TTE) following repair of her ventricular septal defect (VSD).
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http://dx.doi.org/10.1111/echo.15165DOI Listing
August 2021

Does Life Satisfaction Vary with Time and Income? Investigating the Relationship Among Free Time, Income, and Life Satisfaction.

J Happiness Stud 2021 Jun 3;22:2051-2073. Epub 2020 Sep 3.

The Nature Conservancy, Santa Cruz, CA 95060, USA.

Time and income are distinct and critical resources needed in the pursuit of happiness (life satisfaction). Income can be used to purchase market goods and services, and time can be used to spend time with friends and family, rest and sleep, and other activities. Yet little research has examined how different combinations of time and income affect life satisfaction, and if more of both is positively associated with greater levels of life satisfaction. We investigate whether life satisfaction significantly varies with time and income using data from the American Time Use Survey and its well-being module, which is a nationally representative sample of over 5000 US respondents over the age of 15. We plot a three-dimensional space exploring the relationship among time, income, and life satisfaction, finding people with similar incomes with less free time have lower levels of life satisfaction. We also identify different four subpopulations, three of which have low well-being along time and income, and one with high well-being along time and income. These sub-groups significantly differ along key characteristics. Respondents with less free time and low income-the doubly poor-are more likely to be female, less educated, and have more than two kids and young children. Those with low income but lots of time, in comparison, are more likely to be black, unemployed, and have some physical or cognitive difficult. We conclude that time provides unique insights into human well-being that income alone cannot capture and should be further incorporated into research and policy on life satisfaction.
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http://dx.doi.org/10.1007/s10902-020-00307-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8336732PMC
June 2021

A Review of the Parasitic Isopod Genus Nierstrasz & Brender à Brandis, 1931 (Crustacea: Isopoda: Epicaridea), Parasites of Cyclodorippoid Crabs (Crustacea: Decapoda: Brachyura), with Description of a New Species from New Caledonia.

Zool Stud 2021 24;60:e4. Epub 2021 Feb 24.

Department of Biology, Hofstra University, Hempstead, NY 11549, USA. E-mail: (Williams).

A new species of the parasitic isopod genus Nierstrasz & Brender à Brandis, 1931 (Isopoda: Bopyridae) found parasitizing the cyclodorippoid crab host Tan & Huang, 2000 is described from New Caledonia. Females of n. sp. can be distinguished from those of the other two species in the genus in length to width ratio, pleopodal endopod morphology, and structure of the barbula. We review the two previously described species of from Stimpson, 1858 hosts based on type specimens of Nierstrasz & Brender à Brandis, 1931 from Indonesia and type specimens plus new material of Nierstrasz & Brender à Brandis, 1931 from Japan. New details previously omitted from the original descriptions and a key to species of based on female and male specimens are provided.
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http://dx.doi.org/10.6620/ZS.2021.60-04DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8292842PMC
February 2021

Longitudinal exposure to consumer product chemicals and changes in plasma oxylipins in pregnant women.

Environ Int 2021 12 24;157:106787. Epub 2021 Jul 24.

Epidemiology Branch, National Institute of Environmental Health Sciences (NIEHS), United States. Electronic address:

Background: Exposure to consumer product chemicals during pregnancy may increase susceptibility to pregnancy disorders by influencing maternal inflammation. However, effects on specific inflammatory pathways have not been well characterized. Oxylipins are a diverse class of lipids that act as important mediators and biomarkers of several biological pathways that regulate inflammation. Adverse pregnancy outcomes have been associated with circulating oxylipin levels in pregnancy. In this study, we aimed to determine the longitudinal associations between plasma oxylipins and urinary biomarkers of three classes of consumer product chemicals among pregnant women.

Methods: Data come from a study of 90 pregnant women nested within the LIFECODES cohort. Maternal plasma and urine were collected at three prenatal visits. Plasma was analyzed for 61 oxylipins, which were grouped according to biosynthetic pathways that we defined by upstream: 1) fatty acid precursor, including linoleic, arachidonic, docosahexaenoic, or eicosapentaenoic acid; and 2) enzyme pathway, including cyclooxygenase (COX), lipoxygenase (LOX), or cytochrome P450 (CYP). Urine was analyzed for 12 phenol, 12 phthalate, and 9 organophosphate ester (OPE) biomarkers. Linear mixed effect models were used for single-pollutant analyses. We implemented a novel extension of quantile g-computation for longitudinal data to examine the joint effect of class-specific chemical mixtures on individual plasma oxylipin concentrations.

Results: We found that urinary biomarkers of consumer product chemicals were positively associated with pro-inflammatory oxylipins from several biosynthetic pathways. Importantly, these associations depended upon the chemical class of exposure biomarker. We estimated positive associations between urinary phenol biomarkers and oxylipins produced from arachidonic acid by LOX enzymes, including several important pro-inflammatory hydroxyeicosatetraenoic acids (HETEs). On average, mean concentrations of oxylipin produced from the arachidonic acid/LOX pathway were 48%-71% higher per quartile increase in the phenol biomarker mixture. For example, a simultaneous quartile increase in all urinary phenols was associated with 53% higher (95% confidence interval [CI]: 11%, 111%) concentrations of 12-HETE. The positive associations among phenols were primarily driven by methyl paraben, 2,5-dichlorophenol, and triclosan. Additionally, we observed that phthalate and OPE metabolites were associated with higher concentrations of oxylipins produced from linoleic acid by CYP enzymes, including the pro-inflammatory dihydroxy-octadecenoic acids (DiHOMEs). Associations among DiHOME oxylipins were driven by metabolites of benzylbutyl and di-isodecyl phthalate, and by the metabolite of tris(1,3-dichloro-2-propyl) phosphate among OPEs. We also observed inverse associations between phthalate and OPE metabolites and oxylipins produced from other pathways; however, adjusting for a plasma indicator of dietary fatty acid intake attenuated those results.

Conclusions: Our findings support the hypothesis that consumer product chemicals may have diverse impacts on inflammation processes in pregnancy. Certain pro-inflammatory oxylipins were generally higher among participants with higher urinary chemical biomarker concentrations. Associations varied by class of chemical and by the biosynthetic pathway of oxylipin production, indicating potential specificity in the inflammatory effects of these environmental chemicals during pregnancy that warrant investigation in larger studies.
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http://dx.doi.org/10.1016/j.envint.2021.106787DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8490329PMC
December 2021

Recognizing Subacute Combined Degeneration in Patients With Normal Vitamin B12 Levels.

Cureus 2021 Jun 3;13(6):e15429. Epub 2021 Jun 3.

Internal Medicine, Emory University School of Medicine, Atlanta, USA.

Vitamin B12 deficiency is commonly associated with dementia in patients over the age of 65 years; however, it can affect people of all ages. Recognizing the clinical sequelae of subacute combined degeneration is essential for the timely diagnosis and treatment of vitamin B12 deficiency. In this report, we describe a case of a young man presenting with several months of neuropathy, depression, and abdominal symptoms. His initial vitamin B12 levels were within normal limits, but an elevated methylmalonic acid level and subacute combined degeneration of his spine on MRI confirmed the diagnosis of vitamin B12 deficiency. The patient later tested positive for autoantibodies associated with pernicious anemia. His symptoms improved with intramuscular injections of cyanocobalamin. This case highlights the importance of recognizing vitamin B12 deficiency in patients of all age groups even in the setting of apparently "normal" B12 levels.
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http://dx.doi.org/10.7759/cureus.15429DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8254577PMC
June 2021

Segmented worms (Phylum Annelida): a celebration of twenty years of progress through Zootaxa and call for action on the taxonomic work that remains.

Zootaxa 2021 May 28;4979(1):190211. Epub 2021 May 28.

Department of Biology, Hofstra University, Hempstead, NY 02125 USA..

Zootaxa has been the leading journal on invertebrate systematics especially within Annelida. Our current estimates indicate annelids include approximately 20,200 valid species of polychaetes, oligochaetes, leeches, sipunculans and echiurans. We include herein the impact of Zootaxa on the description of new annelid species in the last two decades. Since 2001, there have been over 1,300 new annelid taxa published in about 630 papers. The majority of these are polychaetes (921 new species and 40 new genera) followed by oligochaetes (308 new species and 10 new genera) and leeches (21 new species). The numerous papers dealing with new polychaete species have provided us a clear picture on which polychaete families have had the most taxonomic effort and which authors and countries have been the most prolific of descriptions of new taxa. An estimated additional 10,000+ species remain to be described in the phylum, thus we urge annelid workers to continue their efforts and aid in training a new generation of taxonomists focused on this ecologically important group.
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http://dx.doi.org/10.11646/zootaxa.4979.1.18DOI Listing
May 2021

Single-stage Latissimus Dorsi Breast Reconstruction Using Spectrum Devices: Outcomes and Technique.

Plast Reconstr Surg Glob Open 2021 May 3;9(5):e3282. Epub 2021 May 3.

Division of Plastic and Reconstructive Surgery, Dalhousie University, Halifax, Nova Scotia, Canada.

Background: Latissimus dorsi (LD) flap is a workhorse flap in breast reconstruction. Despite many advantages, the primary criticism of this flap is the requirement of a second surgery to exchange expansion devices for permanent implants. This study reports a single-stage reconstruction and outcomes wherein Spectrum devices (Mentor, Irving, TX), which serve as expanders and permanent implants, are used, and expansion ports are removed under local anesthetic.

Methods: A retrospective chart review of all patients undergoing LD flap reconstruction with Spectrum device by a single surgeon at a single center during a 10-year period was performed. All patients, unilateral/bilateral, immediate/delayed were included. Details of implants, surgical procedure(s), and follow-up visits were assessed for patient outcomes.

Results: In total, 41 patients and 56 breasts were included. Of the total patients, 58.5% retained the Spectrum device and had the expansion port removed under local anesthetic. An estimated 6 major complications occurred (14.6%), requiring return to the operating room: 3 patients required a capsulectomy, 1 a capsulotomy/implant repositioning, one had loss of implant (infection), and 1 had venous congestion of the flap. Eleven minor complications occurred (26.8%): 5 seromas (3 at the breast site, 2 at the donor site), 3 delayed wound healings (2 at donor site, 1 at breast site), 1 mastectomy flap necrosis, 2 infections (1 at each breast site, 1 at donor site).

Conclusions: This study provides details of a single-stage LD flap with Spectrum device breast reconstruction that can be considered when performing an LD reconstruction. This technique is efficient and safe with comparable complication profile.
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http://dx.doi.org/10.1097/GOX.0000000000003282DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8092368PMC
May 2021

Causes of Death in Infants and Children with Congenital Heart Disease.

Pediatr Cardiol 2021 Aug 22;42(6):1308-1315. Epub 2021 Apr 22.

Department of Pediatrics, Division of Pediatric Cardiology, Duke University Medical Center, Box 3090, Durham, NC, 27710, USA.

With improved surgical outcomes, infants and children with congenital heart disease (CHD) may die from other causes of death (COD) other than CHD. We sought to describe the COD in youth with CHD in North Carolina (NC). Patients from birth to 20 years of age with a healthcare encounter between 2008 and 2013 in NC were identified by ICD-9 code. Patients who could be linked to a NC death certificate between 2008 and 2016 were included. Patients were divided by CHD subtypes (severe, shunt, valve, other). COD was compared between groups. Records of 35,542 patients < 20 years old were evaluated. There were 15,277 infants with an annual mortality rate of 3.5 deaths per 100 live births. The most frequent COD in infants (age < 1 year) were CHD (31.7%), lung disease (16.1%), and infection (11.4%). In 20,265 children (age 1 to < 20 years), there was annual mortality rate of 9.7 deaths per 1000 at risk. The most frequent COD in children were CHD (34.2%), neurologic disease (10.2%), and infection (9.5%). In the severe subtype, CHD was the most common COD. In infants with shunt-type CHD disease, lung disease (19.5%) was the most common COD. The mortality rate in infants was three times higher when compared to children. CHD is the most common underlying COD, but in those with shunt-type lesions, extra-cardiac COD is more common. A multidisciplinary approach in CHD patients, where development of best practice models regarding comorbid conditions such as lung disease and neurologic disease could improve outcomes in this patient population.
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http://dx.doi.org/10.1007/s00246-021-02612-2DOI Listing
August 2021

Latent Class Analysis of Individual-Level Characteristics Predictive of Intervention Outcomes in Urban Male Adolescents.

Res Child Adolesc Psychopathol 2021 09 5;49(9):1139-1149. Epub 2021 Apr 5.

RTI International, Research Triangle Park, Durham, North Carolina, USA.

Preventive intervention research dictates that new techniques are needed to elucidate what types of interventions work best for whom to prevent behavioral problems. The current investigation applies a latent class modeling structure to identify the constellation of characteristics-or profile-in urban male adolescents (n = 125, aged 15) that interrelatedly predict responses to a brief administration of an evidence-based program, Positive Adolescent Choices Training (PACT). Individual-level characteristics were selected as predictors on the basis of their association with risk behaviors and their implication in intervention outcomes (e.g., mental health, stress exposure, temperament, cognitive function, stress reactivity and emotion perception). Outcome measures included virtual reality vignettes and questionnaire-style role play scenarios to gauge orientations around aggressive conflict resolution, communication, emotional control, beliefs supporting aggression and hostility. A three-class model was found to best fit the data: "NORMative" (NORM), with relatively low symptomatology; "Mental Health" problems (MH-I) with elevated internalizing symptoms; and "Mental Health-E + Cognitive Deficit" (MH-E + Cog) with elevated mental health symptoms paired with cognitive decrements. The NORM class had positive PACT effects for communication, conflict resolution, and aggressive beliefs. Moderation was evidenced by lack of positive PACT effects for the MH-I and MH-E + Cog groups. Also, PACT classes with MH issues showed marginally significant worsening of aggressive beliefs compared to control students in the same class. Results suggest that a latent class model may identify "signatures" or profiles of traits, experiences and other influences that collectively-and more realistically-predict variable intervention outcomes with implications for more effectively targeting interventions than singular factors.
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http://dx.doi.org/10.1007/s10802-021-00808-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8496900PMC
September 2021

A Latent Class Analysis of Prevention Approaches Used to Reduce Community-Level Prescription Drug Misuse in Adolescents and Young Adults.

J Prim Prev 2021 Jun 3;42(3):279-296. Epub 2021 Apr 3.

RTI International, Division of Behavioral Health Research, 701 13th Street, NW, Suite 750, Washington, DC, 20005, USA.

The Substance Abuse and Mental Health Services Administration's Strategic Prevention Framework Partnerships for Success (PFS) program supports community-based organizations (CBOs) across the United States in implementing evidence-based prevention interventions to reduce substance use in adolescents and young adults. Little attention has been paid to how CBOs combine interventions to create comprehensive community-specific prevention approaches, or whether different approaches achieve similar community-level effects on prescription drug misuse (PDM). We used PFS evaluation data to address these gaps. Over 200 CBOs reported their prevention intervention characteristics, including strategy type (e.g., prevention education, environmental strategies) and number of unique interventions. Evaluation staff coded whether each intervention was an evidence-based program, practice, or policy (EBPPP). Latent Class Analysis of seven characteristics (use of each of five strategy types, use of one or more EBPPP, and number of interventions implemented) identified six prevention approach profiles: High Implementation EBPPP, Media Campaigns, Environmental EBPPP, High Implementation Non-EBPPP, Prevention Education, and Other Information Dissemination. All approaches except Media Campaigns and Other Information Dissemination were associated with significant reductions in community-level PDM. These approaches may need to be paired with other, more direct, prevention activities to effectively reduce PDM at the community level. However, similar rates of change in PDM across all 6 prevention approaches suggests only weak evidence favoring use of the other four approaches. Community-based evaluations that account for variability in implemented prevention approaches may provide a more nuanced understanding of community-level effects. Additional work is needed to help CBOs identify the most appropriate approach to use based on their target communities' characteristics and resources.
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http://dx.doi.org/10.1007/s10935-021-00631-6DOI Listing
June 2021

UDP-glucose and P2Y14 receptor amplify allergen-induced airway eosinophilia.

J Clin Invest 2021 04;131(7)

Immunity, Inflammation and Disease Laboratory.

Airway eosinophilia is a hallmark of allergic asthma and is associated with mucus production, airway hyperresponsiveness, and shortness of breath. Although glucocorticoids are widely used to treat asthma, their prolonged use is associated with several side effects. Furthermore, many individuals with eosinophilic asthma are resistant to glucocorticoid treatment, and they have an unmet need for novel therapies. Here, we show that UDP-glucose (UDP-G), a nucleotide sugar, is selectively released into the airways of allergen-sensitized mice upon their subsequent challenge with that same allergen. Mice lacking P2Y14R, the receptor for UDP-G, had decreased airway eosinophilia and airway hyperresponsiveness compared with wild-type mice in a protease-mediated model of asthma. P2Y14R was dispensable for allergic sensitization and for the production of type 2 cytokines in the lung after challenge. However, UDP-G increased chemokinesis in eosinophils and enhanced their response to the eosinophil chemoattractant, CCL24. In turn, eosinophils triggered the release of UDP-G into the airway, thereby amplifying eosinophilic recruitment. This positive feedback loop was sensitive to therapeutic intervention, as a small molecule antagonist of P2Y14R inhibited airway eosinophilia. These findings thus reveal a pathway that can be therapeutically targeted to treat asthma exacerbations and glucocorticoid-resistant forms of this disease.
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http://dx.doi.org/10.1172/JCI140709DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8011887PMC
April 2021

Thermal heterogeneity in the proximity of municipal solid waste landfills on forest and agricultural lands.

J Environ Manage 2021 Jun 13;287:112320. Epub 2021 Mar 13.

Clean Energy Technologies Research Institute, Process Systems Engineering, Faculty of Engineering and Applied Science, University of Regina, 3737 Wascana Parkway, Regina, SK, S4S 0A2, Canada.

Information on the spatial extent of potential impact areas near disposal sites is vital to the development of a sustainable natural resource management policy. Eight Canadian landfills of various sizes and shapes in different climatic conditions are studied to quantify the spatial extent of their bio-thermal zone. Land surface temperature (LST) and normalized difference vegetation index (NDVI) are examined with respect to different Land Use Land Cover (LULC) classes. Within 1500 m of the sites, LST ranged from 18.3 °C to 29.5 °C and 21.3 °C-29.7 °C for forest land and agricultural land, respectively. Linear regression shows a decreasing LST trend in forest land for five out of seven landfills. A similar trend, however, is not observed for agricultural land. Both the magnitude and the variability of LST are higher in agricultural land. The size of the bio-thermal zone is sensitive to the respective LULC class. The approximate bio-thermal zones for forest class and agricultural classes are about 170 ± 90 m and 180 ± 90 m from the landfill perimeter, respectively. For the forest class, NDVI was negatively correlated with LST at six out of seven Canadian landfills, and stronger relationships are observed in the agricultural class. NDVI data has a considerably larger spread and is less consistent than LST. LST data appears more appropriate for identifying landfill bio-thermal zones. A subtle difference in LST is observed among six LULC classes, averaging from 23.9 °C to 27.4 °C. Geometric shape makes no observable difference in LST in this study; however, larger landfill footprint appears to have higher LST.
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http://dx.doi.org/10.1016/j.jenvman.2021.112320DOI Listing
June 2021

An Unusual Association: Total Anomalous Pulmonary Venous Return and Aortic Arch Obstruction in Patients with Cat Eye Syndrome.

J Pediatr Genet 2021 Mar 20;10(1):35-38. Epub 2020 Jan 20.

Division of Pediatric Cardiology, Department of Pediatrics, Duke University Medical Center, Durham, North Carolina, United States.

Cat eye syndrome (CES) is a rare genetic defect, characterized by iris colobomas, preauricular skin tags, and anal malformations. Affecting 1 in 150,000 people, this defect is caused by duplication or triplication of the proximal long (q) arm of chromosome 22. Congenital heart disease is associated with CES. One of the most common heart defects in patients with CES is total anomalous pulmonary venous return (TAPVR). In this article, we reported patients with a rare association of concomitant TAPVR and aortic arch obstruction: one with interrupted aortic arch and the other with coarctation of the aorta with an aberrant right subclavian artery.
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http://dx.doi.org/10.1055/s-0039-1701020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7853914PMC
March 2021

Is Orbicularis Oculi Muscle Resection Necessary in Upper Blepharoplasty? A Systematic Review.

Aesthetic Plast Surg 2021 10 4;45(5):2190-2198. Epub 2021 Feb 4.

Division of Plastic Surgery, Faculty of Medicine, Dalhousie University, Room 4447, Halifax Infirmary, 4th Floor, Plastic Surgery, 1796 Summer Street, Halifax, NS, B3H 3A7, Canada.

Background: Our objective is to evaluate the evidence on the aesthetic effect and complications of skin-OOM strip resection compared to skin only upper blepharoplasty.

Methods: A systematic search of EMBASE, PubMed, Cochrane and Google Scholar databases was performed using our search strategy through to 31 December 2019. Only comparative studies of the two upper blepharoplasty techniques were included. Three reviewers performed study selection process, data extraction, and quality assessment.

Results: A total of six articles were eligible for final inclusion. The included studies consist of two controlled retrospective cohorts and four small randomized controlled studies (RCT). Three of which, were double blinded. Those RCTs were assigned level 2 evidence due to small size and methodological limitations. The sample size of included was studies 407 in the two retrospective studies and 57 in the four RCTs. The outcomes showed that resection of OOM along with skin in upper blepharoplasty showed no difference in long-term aesthetic outcome when skin only procedure is performed. Muscle strip resection was associated with initially higher ophthalmological morbidity (edema, bruising, pain, dry eye, sluggish eye closure and lagopthalmos). Those resolved a few weeks later with conservative treatment.

Conclusion: The resection of OOM along with skin in upper blepharoplasty showed no difference in long-term aesthetic outcome and was associated with initially higher ophthalmological morbidity compared to skin only procedure. While we are not suggesting that OOM resection is never required, the evidence strongly support its preservation during standard upper blepharoplasty.

Level Of Evidence Iii: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to Table of Contents or the online Instructions to Authors www.springer.com/00266 .
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http://dx.doi.org/10.1007/s00266-021-02131-8DOI Listing
October 2021

Induction of ADAM10 by Radiation Therapy Drives Fibrosis, Resistance, and Epithelial-to-Mesenchyal Transition in Pancreatic Cancer.

Cancer Res 2021 Jun 1;81(12):3255-3269. Epub 2021 Feb 1.

Department of Pharmacology, University of Colorado Comprehensive Cancer Center, University of Colorado, Anschutz Medical Campus, Aurora, Colorado.

Stromal fibrosis activates prosurvival and proepithelial-to-mesenchymal transition (EMT) pathways in pancreatic ductal adenocarcinoma (PDAC). In patient tumors treated with neoadjuvant stereotactic body radiation therapy (SBRT), we found upregulation of fibrosis, extracellular matrix (ECM), and EMT gene signatures, which can drive therapeutic resistance and tumor invasion. Molecular, functional, and translational analysis identified two cell-surface proteins, a disintegrin and metalloprotease 10 (ADAM10) and ephrinB2, as drivers of fibrosis and tumor progression after radiation therapy (RT). RT resulted in increased ADAM10 expression in tumor cells, leading to cleavage of ephrinB2, which was also detected in plasma. Pharmacologic or genetic targeting of ADAM10 decreased RT-induced fibrosis and tissue tension, tumor cell migration, and invasion, sensitizing orthotopic tumors to radiation killing and prolonging mouse survival. Inhibition of ADAM10 and genetic ablation of ephrinB2 in fibroblasts reduced the metastatic potential of tumor cells after RT. Stimulation of tumor cells with ephrinB2 FC protein reversed the reduction in tumor cell invasion with ADAM10 ablation. These findings represent a model of PDAC adaptation that explains resistance and metastasis after RT and identifies a targetable pathway to enhance RT efficacy. SIGNIFICANCE: Targeting a previously unidentified adaptive resistance mechanism to radiation therapy in PDAC tumors in combination with radiation therapy could increase survival of the 40% of PDAC patients with locally advanced disease. GRAPHICAL ABSTRACT: http://cancerres.aacrjournals.org/content/canres/81/12/3255/F1.large.jpg.
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http://dx.doi.org/10.1158/0008-5472.CAN-20-3892DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8260469PMC
June 2021

Cryo-EM structures of the SARS-CoV-2 endoribonuclease Nsp15 reveal insight into nuclease specificity and dynamics.

Nat Commun 2021 01 27;12(1):636. Epub 2021 Jan 27.

Signal Transduction Laboratory, National Institute of Environmental Health Sciences, National Institutes of Health, Department of Health and Human Services, 111 T. W. Alexander Drive, Research Triangle Park, NC, 27709, USA.

Nsp15, a uridine specific endoribonuclease conserved across coronaviruses, processes viral RNA to evade detection by host defense systems. Crystal structures of Nsp15 from different coronaviruses have shown a common hexameric assembly, yet how the enzyme recognizes and processes RNA remains poorly understood. Here we report a series of cryo-EM reconstructions of SARS-CoV-2 Nsp15, in both apo and UTP-bound states. The cryo-EM reconstructions, combined with biochemistry, mass spectrometry, and molecular dynamics, expose molecular details of how critical active site residues recognize uridine and facilitate catalysis of the phosphodiester bond. Mass spectrometry revealed the accumulation of cyclic phosphate cleavage products, while analysis of the apo and UTP-bound datasets revealed conformational dynamics not observed by crystal structures that are likely important to facilitate substrate recognition and regulate nuclease activity. Collectively, these findings advance understanding of how Nsp15 processes viral RNA and provide a structural framework for the development of new therapeutics.
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http://dx.doi.org/10.1038/s41467-020-20608-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7840905PMC
January 2021

Advanced Real-Time Process Analytics for Multistep Synthesis in Continuous Flow*.

Angew Chem Int Ed Engl 2021 04 24;60(15):8139-8148. Epub 2021 Feb 24.

Center for Continuous Flow Synthesis and Processing (CCFLOW), Research Center Pharmaceutical Engineering GmbH (RCPE), Inffeldgasse 13, 8010, Graz, Austria.

In multistep continuous flow chemistry, studying complex reaction mixtures in real time is a significant challenge, but provides an opportunity to enhance reaction understanding and control. We report the integration of four complementary process analytical technology tools (NMR, UV/Vis, IR and UHPLC) in the multistep synthesis of an active pharmaceutical ingredient, mesalazine. This synthetic route exploits flow processing for nitration, high temperature hydrolysis and hydrogenation reactions, as well as three inline separations. Advanced data analysis models were developed (indirect hard modeling, deep learning and partial least squares regression), to quantify the desired products, intermediates and impurities in real time, at multiple points along the synthetic pathway. The capabilities of the system have been demonstrated by operating both steady state and dynamic experiments and represents a significant step forward in data-driven continuous flow synthesis.
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http://dx.doi.org/10.1002/anie.202016007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8048486PMC
April 2021

Discovery, Function, and Therapeutic Targeting of Siglec-8.

Cells 2020 12 24;10(1). Epub 2020 Dec 24.

Division of Allergy and Immunology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA.

Siglecs (sialic acid-binding immunoglobulin-like lectins) are single-pass cell surface receptors that have inhibitory activities on immune cells. Among these, Siglec-8 is a CD33-related family member selectively expressed on human mast cells and eosinophils, and at low levels on basophils. These cells can participate in inflammatory responses by releasing mediators that attract or activate other cells, contributing to the pathogenesis of allergic and non-allergic diseases. Since its discovery in 2000, initial in vitro studies have found that the engagement of Siglec-8 with a monoclonal antibody or with selective polyvalent sialoglycan ligands induced the cell death of eosinophils and inhibited mast cell degranulation. Anti-Siglec-8 antibody administration in vivo to humanized and transgenic mice selectively expressing Siglec-8 on mouse eosinophils and mast cells confirmed the in vitro findings, and identified additional anti-inflammatory effects. AK002 (lirentelimab) is a humanized non-fucosylated IgG1 antibody against Siglec-8 in clinical development for mast cell- and eosinophil-mediated diseases. AK002 administration has safely demonstrated the inhibition of mast cell activity and the depletion of eosinophils in several phase 1 and phase 2 trials. This article reviews the discovery and functions of Siglec-8, and strategies for its therapeutic targeting for the treatment of eosinophil- and mast cell-associated diseases.
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http://dx.doi.org/10.3390/cells10010019DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7823959PMC
December 2020

Paddling Upstream With Point-of-Care Ultrasound to Diagnose Cardiac Ascites.

Cureus 2020 Nov 21;12(11):e11604. Epub 2020 Nov 21.

Medicine, Atlanta Veterans Affairs Medical Center, Atlanta, USA.

Ascites has multiple etiologies, including cirrhosis and heart failure, which can be differentiated by point-of-care ultrasound (POCUS). One cause of cardiac ascites that can be difficult to identify is portopulmonary hypertension (PPH), a rare disorder caused by pulmonary artery vasoconstriction due to advanced liver disease. POCUS can readily identify right ventricular dysfunction which can accelerate a PPH diagnosis. This case report describes the use of POCUS to work-up new onset ascites and expedite diagnosis of cardiac ascites due to PPH.
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http://dx.doi.org/10.7759/cureus.11604DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7752799PMC
November 2020

Impella 5.5 Direct Aortic Implant and Explant Techniques.

Ann Thorac Surg 2021 05 17;111(5):e373-e375. Epub 2020 Dec 17.

Singing River Health System, Ocean Springs, Mississippi.

The Impella 5.5 with SmartAssist system (Abiomed, Danvers, MA) is approved for the treatment of cardiogenic shock after acute myocardial infarction, cardiac surgery, or in the setting of cardiomyopathy. Designed for full circulatory support and left ventricular unloading the system comprises a catheter-based microaxial pump placed across the aortic valve, pulling blood from the left ventricle and into the ascending aorta. Implantation can be approached through the axillary artery or directly into the aortic root. We present several technical options for implanting, tunneling, and explanting the system using the direct aortic approach and allowing for bedside removal.
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http://dx.doi.org/10.1016/j.athoracsur.2020.09.069DOI Listing
May 2021

Lrp1 Regulation of Pulmonary Function. Follow-Up of Human GWAS in Mice.

Am J Respir Cell Mol Biol 2021 03;64(3):368-378

Immunity, Inflammation, and Disease Laboratory.

Human genome-wide association studies (GWASs) have identified more than 270 loci associated with pulmonary function; however, follow-up studies to determine causal genes at these loci are few. SNPs in low-density lipoprotein receptor-related protein 1 (LRP1) are associated with human pulmonary function in GWASs. Using murine models, we investigated the effect of genetic disruption of the gene in smooth muscle cells on pulmonary function in naive animals and after exposure to bacterial LPS or house dust mite extract. Disruption of in smooth muscle cells leads to an increase in tissue resistance, elastance, and tissue elastance at baseline. Furthermore, disruption of in smooth muscle increases airway responsiveness as measured by increased total lung resistance and airway resistance after methacholine. Immune cell counts in BAL fluid were increased in animals with disruption. The difference in airway responsiveness by genotype observed in naive animals was not observed after LPS or house dust mite extract exposure. To further explore the mechanisms contributing to changes in pulmonary function, we identified several ligands dysregulated with disruption in smooth muscle cells. These data suggest that dysregulation of LRP1 in smooth muscle cells affects baseline pulmonary function and airway responsiveness and helps establish as the causal gene at this GWAS locus.
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http://dx.doi.org/10.1165/rcmb.2019-0444OCDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7909338PMC
March 2021

Social Emotional Learning Program Boosts Early Social and Behavioral Skills in Low-Income Urban Children.

Front Psychol 2020 4;11:561196. Epub 2020 Nov 4.

Human Development and Family Studies, The Pennsylvania State University, University Park, PA, United States.

Social emotional learning (SEL) programs are increasingly being implemented in elementary schools to facilitate development of social competencies, decision-making skills, empathy, and emotion regulation and, in effect, prevent poor outcomes such as school failure, conduct problems, and eventual substance abuse. SEL programs are designed to foster these abilities in children with a wide range of behavioral, social, and learning needs in the classroom, including children who are economically disadvantaged. In a previous study of kindergartners residing in a high-poverty community ( = 327 at baseline), we observed significant behavioral improvements in children receiving an SEL program-The PATHS curriculum (PATHS)-relative to an active control condition within one school year. The present investigation sought to determine whether these improvements were sustained over the course of two school years with intervention and an additional year when intervention was no longer provided. Further, using multilevel models, we examined whether baseline measures of neurocognition and stress physiology-known to be adversely impacted by poverty-moderated heterogeneous outcomes. Finally, a preliminary linear regression analysis explored whether neurocognition and physiological stress reactivity (heart rate variability, HRV) predict change in outcomes postintervention. Results confirmed that students who received PATHS sustained significant behavioral improvements over time. These effects occurred for the full sample, irrespective of putative baseline moderators, suggesting that children in high-risk environments may benefit from SEL interventions irrespective of baseline cognitive functioning as a function of overall substantial need. Of interest is that our exploratory analysis of change from waves three to four after the intervention concluded brought to light possible moderation by baseline physiology. Should subsequent studies confirm this finding, one plausible explanation may be that, when an intervention providing protective effects is withdrawn, children with higher HRV may not be able to regulate physiological stress responses to environmental challenges, leading to an uptick in maladaptive behaviors. In reverse, children with lower HRV-generally associated with poorer emotion regulation-may incur relatively greater gains in behavioral improvement due to lesser sensitivity to the environment, enabling them to continue to accrue benefits. Results are discussed in the context of possible pathways that may be relevant to understanding the special needs of children reared in very low-income, high-stress neighborhoods.
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http://dx.doi.org/10.3389/fpsyg.2020.561196DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7673142PMC
November 2020

Continuous flow synthesis of arylhydrazines nickel/photoredox coupling of -butyl carbazate with aryl halides.

Chem Commun (Camb) 2020 Nov;56(93):14621-14624

Center for Continuous Flow Synthesis and Processing (CC FLOW), Research Center Pharmaceutical Engineering GmbH (RCPE), Inffeldgasse 13, 8010 Graz, Austria. and Institute of Chemistry, University of Graz, NAWI Graz, Heinrichstrasse 28, 8010 Graz, Austria.

Nickel/photoredox catalyzed C-N couplings of hydrazine-derived nucleophiles provide a powerful alternative to Pd-catalyzed methods. This continuous-flow photochemical protocol, optimized using design of experiments, achieves these couplings in short residence times, with high selectivity. A range of (hetero)aryl bromides and chlorides are compatible and understanding of process stability/reactor fouling has been discerned.
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http://dx.doi.org/10.1039/d0cc06787cDOI Listing
November 2020
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