Publications by authors named "James Collins"

682 Publications

Clinically relevant mutations in core metabolic genes confer antibiotic resistance.

Science 2021 02;371(6531)

Institute for Medical Engineering and Science and Department of Biological Engineering, Massachusetts Institute of Technology (MIT), Cambridge, MA, USA.

Although metabolism plays an active role in antibiotic lethality, antibiotic resistance is generally associated with drug target modification, enzymatic inactivation, and/or transport rather than metabolic processes. Evolution experiments of rely on growth-dependent selection, which may provide a limited view of the antibiotic resistance landscape. We sequenced and analyzed adapted to representative antibiotics at increasingly heightened metabolic states. This revealed various underappreciated noncanonical genes, such as those related to central carbon and energy metabolism, which are implicated in antibiotic resistance. These metabolic alterations lead to lower basal respiration, which prevents antibiotic-mediated induction of tricarboxylic acid cycle activity, thus avoiding metabolic toxicity and minimizing drug lethality. Several of the identified metabolism-specific mutations are overrepresented in the genomes of >3500 clinical pathogens, indicating clinical relevance.
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http://dx.doi.org/10.1126/science.aba0862DOI Listing
February 2021

Using deep learning for dermatologist-level detection of suspicious pigmented skin lesions from wide-field images.

Sci Transl Med 2021 Feb;13(581)

Institute for Medical Engineering and Science, Massachusetts Institute of Technology, 77 Massachusetts Ave, Cambridge, MA 02139, USA.

A reported 96,480 people were diagnosed with melanoma in the United States in 2019, leading to 7230 reported deaths. Early-stage identification of suspicious pigmented lesions (SPLs) in primary care settings can lead to improved melanoma prognosis and a possible 20-fold reduction in treatment cost. Despite this clinical and economic value, efficient tools for SPL detection are mostly absent. To bridge this gap, we developed an SPL analysis system for wide-field images using deep convolutional neural networks (DCNNs) and applied it to a 38,283 dermatological dataset collected from 133 patients and publicly available images. These images were obtained from a variety of consumer-grade cameras (15,244 nondermoscopy) and classified by three board-certified dermatologists. Our system achieved more than 90.3% sensitivity (95% confidence interval, 90 to 90.6) and 89.9% specificity (89.6 to 90.2%) in distinguishing SPLs from nonsuspicious lesions, skin, and complex backgrounds, avoiding the need for cumbersome individual lesion imaging. We also present a new method to extract intrapatient lesion saliency (ugly duckling criteria) on the basis of DCNN features from detected lesions. This saliency ranking was validated against three board-certified dermatologists using a set of 135 individual wide-field images from 68 dermatological patients not included in the DCNN training set, exhibiting 82.96% (67.88 to 88.26%) agreement with at least one of the top three lesions in the dermatological consensus ranking. This method could allow for rapid and accurate assessments of pigmented lesion suspiciousness within a primary care visit and could enable improved patient triaging, utilization of resources, and earlier treatment of melanoma.
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http://dx.doi.org/10.1126/scitranslmed.abb3652DOI Listing
February 2021

Racism, history and medical education.

Arch Dis Child 2021 Feb 17. Epub 2021 Feb 17.

Pediatrics, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA.

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http://dx.doi.org/10.1136/archdischild-2020-320448DOI Listing
February 2021

Delphi Project on the trends in Implant Dentistry in the COVID-19 era: Perspectives from Latin America.

Clin Oral Implants Res 2021 Feb 17. Epub 2021 Feb 17.

ETEP (Etiology and Therapy of Periodontal and Peri-Implant Diseases) Research Group, University Complutense, Madrid, Spain.

Aim: To establish trends in Implant Dentistry in Latin America in the Covid-19 pandemic.

Material And Methods: A steering committee and an advisory group of experts in Implant Dentistry were selected among eighteen countries. An open-ended questionnaire by Delphi methodology was validated including 64 questions, divided in 7 topics concerning the various trends in dental implantology. The survey was conducted in two rounds, which provided the participants in the second round with the results of the first. The questionnaires were completed on August 2020 and the online meeting conference was held on September 2020. The final prediction was developed through consensus by a selected group of experts.

Results: A total of 197 experts from Latin America answered the first and second questionnaire. In the first round, the established threshold for consensus (65%) was achieved in 30 questions (46.87%). In the second round, performed on average 45 days later, this level was achieved in 47 questions (73.43%). Consensus was completely reached on the item "Diagnostic" (100%), The field with the lowest consensus was "Demand for treatment with dental implants" (37.5%).

Conclusions: The present study in Latin America has provided relevant and useful information on the predictions in the education and practice of Implant Dentistry in the Covid-19 era. The consensus points towards a great confidence of clinicians in the biosecurity protocols used to minimize the risk of SARS COV-2 transmission. It is foreseen an important change in education, with introduction of virtual reality and other simulation technologies in implant training.
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http://dx.doi.org/10.1111/clr.13723DOI Listing
February 2021

Of bowels, brain and behavior: A role for the gut microbiota in psychiatric comorbidities in irritable bowel syndrome.

Neurogastroenterol Motil 2021 Mar 13;33(3):e14095. Epub 2021 Feb 13.

APC Microbiome Ireland, University College Cork, Cork, Ireland.

Background: The gastrointestinal microbiota has emerged as a key regulator of gut-brain axis signalling with important implications for neurogastroenterology. There is continuous bidirectional communication between the gut and the brain facilitated by neuronal, endocrine, metabolic, and immune pathways. The microbiota influences these signalling pathways via several mechanisms. Studies have shown compositional and functional alterations in the gut microbiota in stress-related psychiatric disorders. Gut microbiota reconfigurations are also a feature of irritable bowel syndrome (IBS), a gut-brain axis disorder sharing high levels of psychiatric comorbidity including both anxiety and depression. It remains unclear how the gut microbiota alterations in IBS align with both core symptoms and these psychiatric comorbidities.

Methods: In this review, we highlight common and disparate features of these microbial signatures as well as the associated gut-brain axis signalling pathways. Studies suggest that patients with either IBS, depression or anxiety, alone or comorbid, present with alterations in gut microbiota composition and harbor immune, endocrine, and serotonergic system alterations relevant to the common pathophysiology of these comorbid conditions.

Key Results: Research has illustrated the utility of fecal microbiota transplantation in animal models, expanding the evidence base for a potential causal role of disorder-specific gut microbiota compositions in symptom set expression. Moreover, an exciting study by Constante and colleagues in this issue highlights the possibility of counteracting this microbiota-associated aberrant behavioral phenotype with a probiotic yeast, Saccharomyces boulardii CNCM I-745.

Conclusions And Inferences: Such data highlights the potential for therapeutic targeting of the gut microbiota as a valuable strategy for the management of comorbid psychiatric symptoms in IBS.
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http://dx.doi.org/10.1111/nmo.14095DOI Listing
March 2021

Synthetic biology in the clinic: engineering vaccines, diagnostics, and therapeutics.

Cell 2021 Feb 10;184(4):881-898. Epub 2021 Feb 10.

Department of Biomedical Engineering, Boston University, Boston, MA 02215, USA; Biological Design Center, Boston University, Boston, MA 02215, USA. Electronic address:

Synthetic biology is a design-driven discipline centered on engineering novel biological functions through the discovery, characterization, and repurposing of molecular parts. Several synthetic biological solutions to critical biomedical problems are on the verge of widespread adoption and demonstrate the burgeoning maturation of the field. Here, we highlight applications of synthetic biology in vaccine development, molecular diagnostics, and cell-based therapeutics, emphasizing technologies approved for clinical use or in active clinical trials. We conclude by drawing attention to recent innovations in synthetic biology that are likely to have a significant impact on future applications in biomedicine.
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http://dx.doi.org/10.1016/j.cell.2021.01.017DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7897318PMC
February 2021

A critical review and meta-analysis of epidemiology studies of occupationally exposed styrene workers evaluated for chromosomal aberration incidence.

Mutat Res 2021 Jan-Feb;861-862:503275. Epub 2020 Oct 22.

Martha M Moore LLC, 23 Alban Lane, Little Rock, Arkansas 72223, United States.

Chromosome aberrations in the peripheral blood lymphocytes of styrene exposed workers have been suggested as a potential early marker for cancer risk. We performed a critical review and abstracted data from all studies using current chromosome aberration scoring criteria and providing at least a mean and standard deviation or standard error for the exposed and comparison groups. Using these data, we conducted a meta-analysis of occupational styrene exposed workers and incidence of chromosome aberrations. Our meta-analysis used the standardized mean difference as the summary statistic since all studies assess the same outcome but use different comparison populations. The primary meta-analysis of the 20 comparisons of 505 styrene exposed workers to 532 comparison workers found a meta-mean difference of 0.361 (95 % CI -0.084 to 0.807, random effects model), but there was substantial lack of consistency across studies (I2 of 90.11, p-value <0.001, fixed effect model). Studies with higher styrene exposures had lower mean standard differences compared to studies with lower styrene exposures. While studies of styrene workers overall had a slight increase in chromosomal aberrations relative to comparison groups, the lack of consistency across studies and the absence of an exposure response and other limitations of the reviewed studies including inadequate exposure assessment, small numbers of participants per study, and poorly matched exposed and comparison workers, we find insufficient evidence to support a conclusion that styrene exposure increases chromosome aberration frequencies in styrene workers.
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http://dx.doi.org/10.1016/j.mrgentox.2020.503275DOI Listing
October 2020

Engineering advanced logic and distributed computing in human CAR immune cells.

Nat Commun 2021 02 4;12(1):792. Epub 2021 Feb 4.

Department of Biomedical Engineering, Boston University, Boston, MA, USA.

The immune system is a sophisticated network of different cell types performing complex biocomputation at single-cell and consortium levels. The ability to reprogram such an interconnected multicellular system holds enormous promise in treating various diseases, as exemplified by the use of chimeric antigen receptor (CAR) T cells as cancer therapy. However, most CAR designs lack computation features and cannot reprogram multiple immune cell types in a coordinated manner. Here, leveraging our split, universal, and programmable (SUPRA) CAR system, we develop an inhibitory feature, achieving a three-input logic, and demonstrate that this programmable system is functional in diverse adaptive and innate immune cells. We also create an inducible multi-cellular NIMPLY circuit, kill switch, and a synthetic intercellular communication channel. Our work highlights that a simple split CAR design can generate diverse and complex phenotypes and provide a foundation for engineering an immune cell consortium with user-defined functionalities.
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http://dx.doi.org/10.1038/s41467-021-21078-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7862674PMC
February 2021

Gingival phenotype and its relationship with different clinical parameters: a study in a Dominican adult sample.

Clin Oral Investig 2021 Jan 29. Epub 2021 Jan 29.

Department of Periodontology, School of Dentistry, Pontificia Universidad Católica Madre y Maestra (PUCMM), Santo Domingo, Dominican Republic.

Objectives: The purpose of this study was to estimate the prevalence of thin and thick gingival phenotype (GPh) in a sample of Dominican subjects and correlate it with clinical parameters.

Materials And Methods: One-hundred seven periodontal healthy volunteers in the range of 18-73 years were enrolled in the study. GPh was defined by the transparency of a periodontal probe through the buccal gingival margin on the upper right or left central incisor. Clinical periodontal parameters such as keratinized gingiva width (WKG), attached gingiva width (WAG), probing depth (PD), plaque index (PI), and gingival index (GI) were recorded by a calibrated examiner. Frequency distribution of qualitative variables was calculated. For quantitative variables, Mann-Whitney and Kruskal-Wallis tests were used for comparison of groups.

Results: There was no association between GPh and sex. There were no significant differences between thin and thick GPh regarding age, PD, GI, and interproximal index. The association between tooth morphology and GPh was significant (p = 0.018). Median amount of keratinized gingiva was significantly larger (p = 0.01) in subjects with thin gingival phenotype (median = 6.00 mm) when compared with subjects with thick gingival phenotype (median = 5 mm).

Conclusions: Subjects with thin GPh presented larger WKG. Furthermore, there was an association between tooth morphology and GPh.

Clinical Relevance: This is the first study to report the distribution of gingival phenotype and its relationship with different periodontal parameters of a Caribbean population. Our findings can contribute to the clinicians when planning or performing dental procedures.
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http://dx.doi.org/10.1007/s00784-021-03806-xDOI Listing
January 2021

The Excess Preterm Birth Rate Among US-Born (Compared to Foreign-Born) Black Women: The Role of Father's Education.

Matern Child Health J 2021 Jan 28. Epub 2021 Jan 28.

Department of Pediatrics, Division of Neonatology, Ann & Robert H. Lurie Children's Hospital of Chicago, #45, 225 E. Chicago Ave, Chicago, IL, 60611, USA.

Objective: To ascertain the component of the excess preterm birth (< 37 weeks, PTB) rate among US-born (compared to foreign-born) Black women attributable to differences in acknowledged father's education attainment.

Methods: Stratified analyses and Oaxaca-Blinder decomposition methods were performed on the 2013 National Center for Health Statistics birth certificate files of singleton infants with acknowledged fathers.

Results: US-born Black women (N = 196,472) had a PTB rate of 13.3%, compared to 10.8% for foreign-born Black women (N = 51,334; Risk Difference (95% confidence interval) = 2.5 (2.3, 2.8). Infants of US-born black women had a greater a percentage of fathers with a high school diploma or less and a lower percentage of fathers with bachelor's degrees or higher than their counterparts of foreign-born women. In both subgroups, PTB rates tended to decline as the level of paternal education attainment rose. In an Oaxaca model (controlling for maternal age, education, marital status, parity, adequacy of prenatal care utilization, and chronic medical conditions), differences in paternal education attainment explained 15% of the maternal nativity disparity in PTB rates. In contrast, maternal education attainment accounted for approximately 4% of the disparity in PTB rates.

Conclusions For Practice: Acknowledged father's low level of education attainment, or something closely related to it, explains a notable proportion of the disparity in PTB rates between US-born and foreign-born Black women.
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http://dx.doi.org/10.1007/s10995-020-03117-9DOI Listing
January 2021

Understanding Racial Disparities of Preterm Birth Through the Placenta.

Clin Ther 2021 Jan 19. Epub 2021 Jan 19.

Ann & Robert H. Lurie Children's Hospital of Chicago, Northwestern University Feinberg School of Medicine, Department of Pediatrics, Division of Neonatology, Chicago, IL, USA.

The racial disparity associated with preterm birth is a public health concern in the United States. The placenta is the principal metabolic, respiratory, and endocrine organ of the fetus and a key route by which environmental exposures are transmitted from mother to offspring. Available at every delivery, it may serve as a marker of differences in prenatal exposures that manifest differently by race. Recently, we described differences in placental pathology between African-American and White preterm births: the prevalence of chronic inflammation was higher among African-American women's placentas compared with those of White women. Similarly, racial differences have been shown in placental malperfusion and placental weight. Social determinants such as poverty and stress from discrimination have been implicated in racial disparities in preterm birth. To date, however, the underlying biological mechanisms, whether through inflammatory, oxidative stress, or other pathways involving epigenetic programming, remain largely unknown. The placenta, complemented by maternal and umbilical cord blood biomarkers, may provide important information on the perinatal environment that explains the origins of racial disparities in preterm birth rates and subsequent health outcomes. This article reviews existing literature and current research gaps. Opportunities are discussed for future placental research that may reveal novel mechanisms leading to the development of new approaches in the prevention and management of preterm birth and its outcomes.
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http://dx.doi.org/10.1016/j.clinthera.2020.12.013DOI Listing
January 2021

RETROSPECTIVE STUDY OF SURGICAL TREATMENT OF REFRACTIVE OSTEOMYELITIS AND INFECTIOUS ARTHRITIS IN THE FLIPPERS OF SEALS IN THE NETHERLANDS.

J Zoo Wildl Med 2020 Nov;51(3):598-605

Sealcentre Pieterburen, Pieterburen, 9968 AG, The Netherlands.

Amputation surgery in pinniped rehabilitation centers is a feasible procedure when animals are presented with open fractures, osteomyelitis, and/or infectious arthritis of the flippers that appear to be refractory to medical treatment. From 2011 to 2017, the Sealcentre Pieterburen in The Netherlands admitted 3,775 seals for rehabilitation. Of these, 37 individuals presented clinical and radiologic signs of bone abnormalities indicative of osteomyelitis or infectious arthritis refractory to medical treatment. Seven cases resulted in euthanasia, and 30 cases underwent amputation surgery. The surgical procedure involved amputation of part of a flipper (24; two animals twice) or of a complete flipper (eight). All procedures were done under general anesthesia except one that was performed with local anesthesia, and all 30 animals were released. In two cases, the osteomyelitis presented with the rare Totenlade phenomenon, a sequestrum surrounded by new periosteal bone formation. The purpose of this retrospective study was to evaluate the outcome of the operative treatment of osteomyelitis and infectious arthritis in the flippers of harbor () and grey seals () during this 6-yr period.
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http://dx.doi.org/10.1638/2018-0221DOI Listing
November 2020

States with more killings of unarmed Black people have larger Black-White preterm birth disparities.

J Perinatol 2021 Feb 15;41(2):358-359. Epub 2021 Jan 15.

Division of Neonatology, Department of Pediatrics, Children's Hospital of Philadelphia and the University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.

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http://dx.doi.org/10.1038/s41372-020-00914-6DOI Listing
February 2021

COVID-19 monthly top five.

Emerg Med J 2021 Jan 15. Epub 2021 Jan 15.

Health Services Research, University of Sheffield, Sheffield, UK.

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http://dx.doi.org/10.1136/emermed-2020-211110DOI Listing
January 2021

Anti-inflammatory effect of salt water and chlorhexidine 0.12% mouthrinse after periodontal surgery: a randomized prospective clinical study.

Clin Oral Investig 2021 Jan 3. Epub 2021 Jan 3.

Department of Periodontology, School of Dental Medicine, Stony Brook University, Stony Brook, NY, USA.

Objectives: The purpose of this study was to compare the anti-inflammatory efficacy of sodium chloride- and a 0.12% chlorhexidine mouth rinses in patients undergoing minimal invasive periodontal surgery.

Materials And Methods: Forty-seven patients with a diagnosis of periodontitis and indication for access flap procedure were randomly selected. Group A: a sodium chloride (salt)water-based mouth rinse (test group) or group B: a 0.12% chlorhexidine mouth rinse (control group) administered after surgery. Gingival Index (GI) were evaluated in the whole mouth and in the surgical site at baseline (T1), a week later (T2), and 12 weeks (T3) after the treatment. Total MMP activity was measured in GCF using a commercial kit and plate reader. Medians of total MMP activity and GI were compared for time intervals T1 vs. T2, T1 vs. T3, and T2 vs T3 using Friedman tests and Wilcoxon signed rank tests, and were also compared between test and control using Mann-WhitneyU tests at each timepoint.

Results: The average GI values showed significant differences between baseline and T2 (p = 0.0005) and baseline and T3 (p = 0.003) in the test group.

Conclusion: The sodium chloride-mouth rinse use after periodontal surgery seems to have similar anti-inflammatory properties as CHX mouth rinse and can be used regularly postoperatively after periodontal surgical procedures.

Clinical Relevance: The use of salt water mouthwash showed an anti-inflammatory effect similar to CHX 0.12% after minimal invasive periodontal surgery. Salt water mouthwash is accessible to the world population and can contribute on the healing process after periodontal surgery.
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http://dx.doi.org/10.1007/s00784-020-03748-wDOI Listing
January 2021

Multisociety guideline on reprocessing flexible GI endoscopes and accessories.

Gastrointest Endosc 2021 Jan;93(1):11-33.e6

Division of Gastroenterology and Hepatology, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA.

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http://dx.doi.org/10.1016/j.gie.2020.09.048DOI Listing
January 2021

Online biology degree program broadens access for women, first-generation to college, and low-income students, but grade disparities remain.

PLoS One 2020 11;15(12):e0243916. Epub 2020 Dec 11.

Biology Education Research Lab, Research for Inclusive STEM Education Center, School of Life Sciences, Arizona State University, Tempe, Arizona, United States of America.

Online education has grown rapidly in recent years with many universities now offering fully online degree programs even in STEM disciplines. These programs have the potential to broaden access to STEM degrees for people with social identities currently underrepresented in STEM. Here, we ask to what extent is that potential realized in terms of student enrollment and grades for a fully online degree program. Our analysis of data from more than 10,000 course-enrollments compares student demographics and course grades in a fully online biology degree program to demographics and grades in an equivalent in-person biology degree program at the same university. We find that women, first-generation to college students and students eligible for federal Pell grants constitute a larger proportion of students in the online program compared to the in-person mode. However, the online mode of instruction is associated with lower course grades relative to the in-person mode. Moreover, African American/Black, Hispanic/Latinx, Native American, and Pacific Islander students as well as federal Pell grant eligible students earned lower grades than white students and non-Pell grant eligible students, respectively, but the grade disparities were similar among both in-person and online student groups. Finally, we find that grade disparities between men and women are larger online compared to in-person, but that for first-generation to college women, the online mode of instruction is associated with little to no grade gap compared to continuing generation women. Our findings indicate that although this online degree program broadens access for some student populations, inequities in the experience remain and need to be addressed in order for online education to achieve its inclusive mission.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0243916PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7732118PMC
February 2021

Identifying a biological signature of prenatal maternal stress.

JCI Insight 2021 Jan 25;6(2). Epub 2021 Jan 25.

APC Microbiome Ireland and.

Psychological stress affects maternal gastrointestinal (GI) permeability, leading to low-grade inflammation, which can negatively affect fetal development. We investigated a panel of circulating markers as a biological signature of this stress exposure in pregnant women with and without the stress-related GI disorder irritable bowel syndrome (IBS). Markers of GI permeability and inflammation were measured in plasma from healthy and IBS cohorts of women at 15 and 20 weeks' gestation. Biomarkers were evaluated with respect to their degree of association to levels of stress, anxiety, and depression as indicated by responses from the Perceived Stress Scale, State-Trait Anxiety Inventory, and Edinburgh Postnatal Depression Scale. High levels of stress were associated with elevations of soluble CD14, lipopolysaccharide binding protein (LBP), and tumor necrosis factor-α, while anxiety was associated with elevated concentrations of C-reactive protein (CRP) in otherwise healthy pregnancies. Prenatal depression was associated with higher levels of soluble CD14, LBP, and CRP in the healthy cohort. High levels of prenatal anxiety and depression were also associated with lower concentrations of tryptophan and kynurenine, respectively, in the IBS cohort. These markers may represent a core maternal biological signature of active prenatal stress, which can be used to inform intervention strategies via stress reduction techniques or other lifestyle approaches. Such interventions may need to be tailored to reflect underlying GI conditions, such as IBS.
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http://dx.doi.org/10.1172/jci.insight.143007DOI Listing
January 2021

Why does racial inequity in health persist?

J Perinatol 2021 Feb 5;41(2):346-350. Epub 2020 Dec 5.

Division of Neonatology, Northwestern University, Ann & Robert H. Lurie Children's Hospital of Chicago, 225 E Chicago Ave, Chicago, IL, 60611, USA.

Attempts over decades have failed to eliminate the glaring inequity in birth outcomes between Americans of different races. We propose broadening the approach to dealing with racial health inequity by considering the interplay of race and class in the politics of the United States. This approach, combined with a grasp of the historical roots of race relations in North America, could hold the promise of improving our country's abysmal showing in international comparisons of population health indicators, including birth outcomes.
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http://dx.doi.org/10.1038/s41372-020-00885-8DOI Listing
February 2021

Schistosoma mansoni venom allergen-like protein 6 (SmVAL6) maintains tegumental barrier function.

Int J Parasitol 2020 Nov 28. Epub 2020 Nov 28.

Institute of Biological, Environmental and Rural Sciences (IBERS), Aberystwyth University, Aberystwyth SY23 3DA, United Kingdom. Electronic address:

The Schistosoma mansoni venom allergen-like protein (SmVAL) superfamily is a collection of at least 29 molecules that have been classified into two distinctive groups (Group 1 and Group 2 SmVALs). The fundamental basis for SmVAL segregation relates to signal peptide and conserved cysteine retention (present in all Group 1 SmVALs, but absent in all Group 2 SmVALs). These structural differences have led to the hypothesis that most Group 1 SmVALs, found as components of schistosome excretory/secretory (E/S) products, predominantly interact with their environment (intermediate or definitive hosts) whereas the Group 2 SmVALs are retained within the schistosome to fulfil parasite-related functions. While experimental evidence to support Group 1 SmVAL/host interactions is growing, similar support for identification of parasite-related Group 2 SmVAL functions is currently lacking. By applying a combination of approaches to the study of SmVAL6, we provide the first known evidence for an essential function of a Group 2 SmVAL in schistosome biology. After whole mount in situ hybridisation (WISH) localised Smval6 to the anterior region of the oesophageal gland (AOG) and cells scattered through the mesenchyme in adult schistosomes, short interfering RNA (siRNA)-mediated silencing of Smval6 was employed to assess loss of function phenotypes. Here, siSmval6-mediated knockdown of transcript and protein levels led to an increase in tegumental permeability as assessed by the quantification of TAMRA-labelled dextran throughout sub-tegumental cells/tissues. Yeast two hybrid screening using SmVAL6 as a bait revealed Sm14 (a fatty acid binding protein) and a dynein light chain (DLC) as directly interacting partners. Interrogation of single-cell RNA-seq (scRNA-seq) data supported these protein interactions by demonstrating the spatial co-expression of Smval6/dlc/Sm14 in a small proportion of adult cell types (e.g. neurons, tegumental cells and neoblasts). In silico modelling of SmVAL6 with Sm14 and DLC provided evidence that opposing faces of SmVAL6 were likely responsible for these protein/protein interactions. Our results suggest that SmVAL6 participates in oesophageal biology, formation of higher order protein complexes and maintenance of tegumental barrier function. Further studies of other Group 2 SmVALs may reveal additional functions of this enigmatic superfamily.
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http://dx.doi.org/10.1016/j.ijpara.2020.09.004DOI Listing
November 2020

Predictive performance of international COVID-19 mortality forecasting models.

medRxiv 2020 Nov 19. Epub 2020 Nov 19.

Forecasts and alternative scenarios of COVID-19 mortality have been critical inputs into a range of policies and decision-makers need information about predictive performance. We identified n=386 public COVID-19 forecasting models and included n=8 that were global in scope and provided public, date-versioned forecasts. For each, we examined the median absolute percent error (MAPE) compared to subsequently observed mortality trends, stratified by weeks of extrapolation, world region, and month of model estimation. Models were also assessed for ability to predict the timing of peak daily mortality. The MAPE among models released in July rose from 1.8% at one week of extrapolation to 24.6% at twelve weeks. The MAPE at six weeks were the highest in Sub-Saharan Africa (34.8%), and the lowest in high-income countries (6.3%). At the global level, several models had about 10% MAPE at six weeks, showing surprisingly good performance despite the complexities of modelling human behavioural responses and government interventions. The framework and publicly available codebase presented here ( https://github.com/pyliu47/covidcompare ) can be routinely used to compare predictions and evaluate predictive performance in an ongoing fashion.
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http://dx.doi.org/10.1101/2020.07.13.20151233DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7685335PMC
November 2020

Evidence that coronavirus superspreading is fat-tailed.

Proc Natl Acad Sci U S A 2020 11 2;117(47):29416-29418. Epub 2020 Nov 2.

Institute for Medical Engineering and Science, Massachusetts Institute of Technology, Cambridge, MA 02139;

Superspreaders, infected individuals who result in an outsized number of secondary cases, are believed to underlie a significant fraction of total SARS-CoV-2 transmission. Here, we combine empirical observations of SARS-CoV and SARS-CoV-2 transmission and extreme value statistics to show that the distribution of secondary cases is consistent with being fat-tailed, implying that large superspreading events are extremal, yet probable, occurrences. We integrate these results with interaction-based network models of disease transmission and show that superspreading, when it is fat-tailed, leads to pronounced transmission by increasing dispersion. Our findings indicate that large superspreading events should be the targets of interventions that minimize tail exposure.
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http://dx.doi.org/10.1073/pnas.2018490117DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7703634PMC
November 2020

Authors' response.

Am J Orthod Dentofacial Orthop 2020 11;158(5):635-636

Santo Domingo, Dominican Republic, and Jequié, Curitiba, and São Paulo, Brazil, and St. Louis, Mo.

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http://dx.doi.org/10.1016/j.ajodo.2020.07.026DOI Listing
November 2020

Authors' response.

Am J Orthod Dentofacial Orthop 2020 11;158(5):634

Santo Domingo, Dominican Republic, and Jequié, Bahia, Curitiba, Paraná, and São Paulo, Brazil, and St. Louis, Mo.

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http://dx.doi.org/10.1016/j.ajodo.2020.07.024DOI Listing
November 2020

Deep-Learning Resources for Studying Glycan-Mediated Host-Microbe Interactions.

Cell Host Microbe 2021 01 28;29(1):132-144.e3. Epub 2020 Oct 28.

Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA 02115, USA; Department of Biological Engineering and Institute for Medical Engineering & Science, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA. Electronic address:

Glycans, the most diverse biopolymer, are shaped by evolutionary pressures stemming from host-microbe interactions. Here, we present machine learning and bioinformatics methods to leverage the evolutionary information present in glycans to gain insights into how pathogens and commensals interact with hosts. By using techniques from natural language processing, we develop deep-learning models for glycans that are trained on a curated dataset of 19,299 unique glycans and can be used to study and predict glycan functions. We show that these models can be utilized to predict glycan immunogenicity and the pathogenicity of bacterial strains, as well as investigate glycan-mediated immune evasion via molecular mimicry. We also develop glycan-alignment methods and use these to analyze virulence-determining glycan motifs in the capsular polysaccharides of bacterial pathogens. These resources enable one to identify and study glycan motifs involved in immunogenicity, pathogenicity, molecular mimicry, and immune evasion, expanding our understanding of host-microbe interactions.
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http://dx.doi.org/10.1016/j.chom.2020.10.004DOI Listing
January 2021

UEFA expert group statement on nutrition in elite football. Current evidence to inform practical recommendations and guide future research.

Br J Sports Med 2020 Oct 23. Epub 2020 Oct 23.

Performance and Research Team, Arsenal Football Club, London, UK

Football is a global game which is constantly evolving, showing substantial increases in physical and technical demands. Nutrition plays a valuable integrated role in optimising performance of elite players during training and match-play, and maintaining their overall health throughout the season. An evidence-based approach to nutrition emphasising, a 'food first' philosophy (ie, food over supplements), is fundamental to ensure effective player support. This requires relevant scientific evidence to be applied according to the constraints of what is practical and feasible in the football setting. The science underpinning sports nutrition is evolving fast, and practitioners must be alert to new developments. In response to these developments, the Union of European Football Associations (UEFA) has gathered experts in applied sports nutrition research as well as practitioners working with elite football clubs and national associations/federations to issue an expert statement on a range of topics relevant to elite football nutrition: (1) match day nutrition, (2) training day nutrition, (3) body composition, (4) stressful environments and travel, (5) cultural diversity and dietary considerations, (6) dietary supplements, (7) rehabilitation, (8) referees and (9) junior high-level players. The expert group provide a narrative synthesis of the scientific background relating to these topics based on their knowledge and experience of the scientific research literature, as well as practical experience of applying knowledge within an elite sports setting. Our intention is to provide readers with content to help drive their own practical recommendations. In addition, to provide guidance to applied researchers where to focus future efforts.
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http://dx.doi.org/10.1136/bjsports-2019-101961DOI Listing
October 2020

Proportional multistate lifetable modelling of preventive interventions: concepts, code and worked examples.

Int J Epidemiol 2020 Oct;49(5):1624-1636

Institute of Health Metrics and Evaluation, University of Washington, Seattle, WA, USA.

Burden of Disease studies-such as the Global Burden of Disease (GBD) Study-quantify health loss in disability-adjusted life-years. However, these studies stop short of quantifying the future impact of interventions that shift risk factor distributions, allowing for trends and time lags. This methodology paper explains how proportional multistate lifetable (PMSLT) modelling quantifies intervention impacts, using comparisons between three tobacco control case studies [eradication of tobacco, tobacco-free generation i.e. the age at which tobacco can be legally purchased is lifted by 1 year of age for each calendar year) and tobacco tax]. We also illustrate the importance of epidemiological specification of business-as-usual in the comparator arm that the intervention acts on, by demonstrating variations in simulated health gains when incorrectly: (i) assuming no decreasing trend in tobacco prevalence; and (ii) not including time lags from quitting tobacco to changing disease incidence. In conjunction with increasing availability of baseline and forecast demographic and epidemiological data, PMSLT modelling is well suited to future multiple country comparisons to better inform national, regional and global prioritization of preventive interventions. To facilitate use of PMSLT, we introduce a Python-based modelling framework and associated tools that facilitate the construction, calibration and analysis of PMSLT models.
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http://dx.doi.org/10.1093/ije/dyaa132DOI Listing
October 2020