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This is a comment to an article previously published in The Depositional Record.

Abstract Infectious etiologies have previously been proposed as causes of both melanoma and non‐melanoma skin cancer. This exploratory overview explains and presents the evidence for the hypothesis that a microorganism excreted in infected ruminant animal feces, Mycobacterium avium subspecies paratuberculosis (MAP), is the cause of some cases of cutaneous melanoma (CM). Occupational, residential, and recreational contact with MAP‐contaminated feces, soil, sand, and natural bodies of water may confer a higher rate of CM. Included in our hypothesis are possible reasons for the differing rates and locations of CM in persons with white versus nonwhite skin, why CM develops underneath nails and in vulvar skin, why canine melanoma is an excellent model for human melanoma, and why the Bacille Calmette‐Guérin (BCG) vaccine has demonstrated efficacy in the prevention and treatment of CM. The pathogenic mechanisms and etiologic aspects of MAP, as a transmittable agent underlying CM risk, are carefully deliberated in this paper. Imbalances in gut and skin bacteria, genetic risk factors, and vaccine prevention/therapy are also discussed, while acknowledging that the evidence for a causal association between MAP exposure and CM remains circumstantial.

Human endogenous retroviruses (HERVs) are remnants of ancient retroviral infections that, over millions of years, became integrated into the human genome. While normally inactive, environmental stimuli such as infections have contributed to the transcriptional reactivation of HERV-promoting pathological conditions, including the development of autoimmunity, neurodegenerative disease and cancer. What infections trigger HERV activation? Mycobacterium avium subspecies paratuberculosis (MAP) is a pluripotent driver of human disease. Aside from granulomatous diseases, Crohn’s disease, sarcoidosis and Blau syndrome, MAP is associated with autoimmune disease: type one diabetes (T1D), multiple sclerosis (MS), rheumatoid arthritis (RA) and autoimmune thyroiditis. MAP is also associated with Alzheimer’s disease (AD) and Parkinson’s disease (PD). Autoimmune diabetes, MS and RA are the diseases with the strongest MAP/HERV association. There are several other diseases associated with HERV activation, including diseases whose epidemiology and/or pathology would prompt speculation for a causal role of MAP. These include non-solar uveal melanoma, colon cancer, glioblastoma and amyotrophic lateral sclerosis (ALS). This article further points to MAP infection as a contributor to autoimmunity, neurodegenerative disease and cancer via the un-silencing of HERV. We examine the link between the ever-increasing number of MAP-associated diseases and the MAP/HERV intersection with these diverse medical conditions, and propose treatment opportunities based upon this association.

Objective: This paper reports on the initial outcomes of a new mHealth intervention to reduce diabetes distress (DD) in families of school-age children living with type 1 diabetes (T1D) entitled, ‘Remedy to Diabetes Distress’ (R2D2). Methods: We randomized 34 families (mean child age = 10 ± 1.4 years; 53% male, 85% White, mean HbA1c = 7.24 ± 0.71%) to one of three delivery arms differing only by number of telehealth visits over a 10-week period: zero visits = self-guided (SG), three visits = enhanced self-guided (ESG), or eight visits = video visits (VV). All families had 24 × 7 access to digital treatment materials for 10 weeks. We examined the feasibility and acceptability of R2D2. We used the Problem Areas in Diabetes-Child (PPAIDC and PAIDC, parent and child, respectively) to examine treatment effects by time and delivery arm. We performed sensitivity analyses to characterize families who responded to R2D2. Results: It was feasible for families to access R2D2 mHealth content independently, though attendance at telehealth visits was variable. Parents and children reported high satisfaction scores. There were significant pre-post reductions in PPAIDC (p = 0.026) and PAIDC (p = 0.026) scores but no differences by delivery arm. There were no differences in child age, sex, race, or pre-treatment HbA1c for responders versus non-responders, though families who responded reported higher PPAID-C scores pre-treatment (p = 0.01) and tended to report shorter diabetes duration (p = 0.08). Conclusions: Initial results support the acceptability and treatment effects of R2D2 regardless of the frequency of adjunctive virtual visits. Characterizing responders may help to identify families who could benefit from R2D2 in the future.

Introduction Diabetes distress (DD) describes the unrelenting emotional and behavioral challenges of living with, and caring for someone living with, type 1 diabetes (T1D). We investigated associations between parent-reported and child-reported DD, T1D device use, and child glycated hemoglobin (HbA1c) in 157 families of school-age children.Research design and methods Parents completed the Parent Problem Areas in Diabetes-Child (PPAID-C) and children completed the Problem Areas in Diabetes-Child (PAID-C) to assess for DD levels. Parents also completed a demographic form where they reported current insulin pump or continuous glucose monitor (CGM) use (ie, user/non-user). We measured child HbA1c using a valid home kit and central laboratory. We used correlations and linear regression for our analyses.Results Children were 49% boys and 77.1% non-Hispanic white (child age (mean±SD)=10.2±1.5 years, T1D duration=3.8±2.4 years, HbA1c=7.96±1.62%). Most parents self-identified as mothers (89%) and as married (78%). Parents’ mean PPAID-C score was 51.83±16.79 (range: 16–96) and children’s mean PAID-C score was 31.59±12.39 (range: 11–66). Higher child HbA1c correlated with non-pump users (r=−0.16, p

A new tridentate Cu2+ complex based on (E)-1-(pyridin-2-yl)-N-(quinolin-8-yl)methanimine (PQM) was generated and characterized to support the activation of diazo compounds for the formation of new C–N bonds. This neutral Schiff base ligand was structurally characterized to coordinate with copper(II) in an equatorial fashion, yielding a distorted octahedral complex. Upon characterization, this copper(II) complex was used to catalyze an efficient and cost-effective protocol for C–N bond formation between N-nucleophiles and copper carbene complexes arising from the activation of diazo carbonyl compounds. A substrate scope of approximately 15 different amine-based substrates was screened, yielding 2° or 3° amine products with acceptable to good yields under mild reaction conditions. Reactivity towards phenol and thiophenol were also screened, showing relatively weak C–O or C–S bond formation under optimized conditions.

Abstract The control of the COVID-19 pandemic in the UK has necessitated restrictions on amateur and professional sports due to the perceived infection risk to competitors, via direct person to person transmission, or possibly via the surfaces of sports equipment. The sharing of sports equipment such as tennis balls was therefore banned by some sport’s governing bodies. We sought to investigate the potential of sporting equipment as transmission vectors of SARS-CoV-2. Ten different types of sporting equipment, including balls from common sports, were inoculated with 40 μl droplets containing clinically relevant concentrations of live SARS-CoV-2 virus. Materials were then swabbed at time points relevant to sports (1, 5, 15, 30, 90 min). The amount of live SARS-CoV-2 recovered at each time point was enumerated using viral plaque assays, and viral decay and half-life was estimated through fitting linear models to log transformed data from each material. At one minute, SARS-CoV-2 virus was recovered in only seven of the ten types of equipment with the low dose inoculum, one at five minutes and none at 15 min. Retrievable virus dropped significantly for all materials tested using the high dose inoculum with mean recovery of virus falling to 0.74% at 1 min, 0.39% at 15 min and 0.003% at 90 min. Viral recovery, predicted decay, and half-life varied between materials with porous surfaces limiting virus transmission. This study shows that there is an exponential reduction in SARS-CoV-2 recoverable from a range of sports equipment after a short time period, and virus is less transferrable from materials such as a tennis ball, red cricket ball and cricket glove. Given this rapid loss of viral load and the fact that transmission requires a significant inoculum to be transferred from equipment to the mucous membranes of another individual it seems unlikely that sports equipment is a major cause for transmission of SARS-CoV-2. These findings have important policy implications in the context of the pandemic and may promote other infection control measures in sports to reduce the risk of SARS-CoV-2 transmission and urge sports equipment manufacturers to identify surfaces that may or may not be likely to retain transferable virus.

Abstract COVID-19 pandemic exerts a health care emergency around the world. The illness severity is heterogeneous. It is mostly unknown why some individuals who are positive for SARS-CoV-2 antibodies stay asymptomatic while others show moderate to severe disease symptoms. Reliable biomarkers for early detection of the disease are urgently needed to attenuate the virus’s spread and help make early treatment decisions. Bioactive sphingolipids play a crucial role in the regulation of viral infections and pro-inflammatory responses involved in the severity of COVID-19. However, any roles of sphingolipids in COVID-19 development or detection remain unknown. In this study, lipidomics measurement of serum sphingolipids demonstrated that reduced sphingosine levels are highly associated with the development of symptomatic COVID-19 in the majority (99.24%) SARS-CoV-2-infected patients compared to asymptomatic counterparts. The majority of asymptomatic individuals (73%) exhibited increased acid ceramidase (AC) in their serum, measured by Western blotting, consistent with elevated sphingosine levels compared to SARS-CoV-2 antibody negative controls. AC protein was also reduced in almost all of the symptomatic patients’ serum, linked to reduced sphingosine levels, measured in longitudinal acute or convalescent COVID-19 samples. Thus, reduced sphingosine levels provide a sensitive and selective serologic biomarker for the early identification of asymptomatic versus symptomatic COVID-19 patients.

Colima is the fourth smallest Mexican state, covering only 0.3% of the surface area of Mexico, but due to the remarkable diversity of physiographic and environmental conditions present in Colima it contains a high biological diversity. We generated an up-to-date herpetofaunal checklist for Colima, with a summary of the conservation status of Colima’s amphibians and reptiles. Our checklist contains a total of 153 species of amphibians and reptiles (three introduced). Thirty-nine are amphibians and 114 are reptiles. More than half of Colima’s herpetofauna are Mexican endemics (66.7% of amphibians, 67.5% of reptiles). Less than 25% of the amphibian and reptile species in Colima are in protected categories according to the IUCN Red List and SEMARNAT. The reptiles in the Marine and Revillagigedo Archipelago regions are the most threatened taxa of the Colima herpetofauna. Colima shares > 80% of its herpetofauna with its neighboring states, Jalisco and Michoacán.

An increased rate of diffuse gliomas, including glioblastoma, has been noted in livestock farmers in Western countries. Some researchers have suggested that a zoonotic virus or bacteria present in the livestock animal’s feces or manure may be a possible etiologic factor. Mycobacterium avium subspecies paratuberculosis (MAP), the cause of a chronic enteropathy in domestic livestock and a probable zoonosis, is heavily excreted in an infected animal’s feces or manure, contaminating soil and ground on the animal’s farm. Once excreted in an animal’s feces, MAP lasts indefinitely in a dormant but viable form, and easily spreads outside farms to the surrounding environment. MAP’s presence throughout the soil in countries where MAP infection of domestic livestock is extensive and longstanding may explain the increased rates of glioblastoma in tennis and baseball players who handle balls coated with MAP-contaminated dirt. MAP infection is consistent with glioblastoma’s two defining histopathologic characteristics; endothelial cell proliferation and pseudopalisading necrosis. MAP is a nontuberculous or atypical mycobacterium, which can cause hypoxic necrotizing granulomas, granulomas that resemble areas of pseudopalisading necrosis, There are known bacterial causes of endothelial cell proliferation. Almost unique amongst intracellular bacteria, MAP’s variant isocitrate dehydrogenase 1 (IDH1) enzyme, a type 2-oxoglutarate ferredoxin oxidoreductase, can utilize a host cell’s cytosolic α-ketoglutarate in its own Krebs or tricarboxylic acid cycle. MAP’s ability to use a host cell’s α-ketoglutarate may explain the survival advantage of the cytosolic IDH1 enzyme mutation for patients with diffuse gliomas including glioblastoma, astrocytoma and oligdendroglioma, a mutation that results in a reduced supply of cytosolic α-ketoglutarate. MAP may therefore be one possible infectious cause of glioblastoma and the other histologic categories of diffuse glioma.

Abstract Infectious agents are known causes of human cancers. Schistosoma japonicum and Schistosoma mansoni cause a percentage of colorectal cancers in countries where the respective Schistosoma species are prevalent. Colorectal cancer is a complication of ulcerative colitis and colonic Crohn’s disease, the two main forms of idiopathic inflammatory bowel disease (IIBD). Mycobacterium avium subspecies paratuberculosis (MAP), the cause of a chronic intestinal disease in domestic and wild ruminants, is one suspected cause of IIBD. MAP may therefore be involved in the pathogenesis of IIBD-associated colorectal cancer as well as colorectal cancer in individuals without IIBD (sporadic colorectal cancer) in countries where MAP infection of domestic livestock is prevalent and MAP’s presence in soil and water is extensive. MAP organisms have been identified in the intestines of patients with sporadic colorectal cancer and IIBD when high magnification, oil immersion light microscopy (×1000 total magnification rather than the usual ×400 total magnification) is used. Research has demonstrated MAP’s ability to invade intestinal goblet cells and cause acute and chronic goblet cell hyperplasia. Goblet cell hyperplasia is the little-recognized initial pathologic lesion of sporadic colorectal cancer, referred to as transitional mucosa, aberrant crypt foci, goblet cell hyperplastic polyps or transitional polyps. It is the even lesser-recognized initial pathologic feature of IIBD, referred to as hypermucinous mucosa, hyperplastic-like mucosal change, serrated epithelial changes, flat serrated changes, goblet cell rich mucosa or epithelial hyperplasia. Goblet cell hyperplasia is the precursor lesion of adenomas and dysplasia in the classical colorectal cancer pathway, of sessile serrated adenomas and serrated dysplasia in the serrated colorectal cancer pathway, and of flat and elevated dysplasia and dysplasia-associated lesions or masses in IIBD-associated intestinal cancers. MAP’s invasion of intestinal goblet cells may result in the initial pathologic lesion of IIBD and sporadic colorectal cancer. MAP’s persistence in infected intestines may result in the eventual development of both IIBD-associated and sporadic colorectal cancer.

As the lipidomics field continues to advance, self-evaluation within the community is critical. Here, we performed an interlaboratory comparison exercise for lipidomics using Standard Reference Material (SRM) 1950–Metabolites in Frozen Human Plasma, a commercially available reference material. The interlaboratory study comprised 31 diverse laboratories, with each laboratory using a different lipidomics workflow. A total of 1,527 unique lipids were measured across all laboratories and consensus location estimates and associated uncertainties were determined for 339 of these lipids measured at the sum composition level by five or more participating laboratories. These evaluated lipids detected in SRM 1950 serve as community-wide benchmarks for intra- and interlaboratory quality control and method validation. These analyses were performed using nonstandardized laboratory-independent workflows. The consensus locations were also compared with a previous examination of SRM 1950 by the LIPID MAPS consortium. While the central theme of the interlaboratory study was to provide values to help harmonize lipids, lipid mediators, and precursor measurements across the community, it was also initiated to stimulate a discussion regarding areas in need of improvement.

Increasing demand for weight reduction and greater fuel efficiency continues to spur the use of composite materials in commercial aircraft structures. Subsequently, as composite aerostructures become larger and more complex, traditional autoclave manufacturing methods are becoming prohibitively expensive. This has prompted renewed interest in out-of-autoclave processing techniques in which resins are introduced into a reinforcing preform. However, the success of these resin infusion methods is highly dependent upon operator skill and experience, particularly in the development of new manufacturing strategies for complex parts. Process modeling, as a predictive computational tool, aims to address the issues of reliability and waste that result from traditional trial-and-error approaches. Basic modeling attempts, many of which are still used in industry, generally focus on simulating fluid flow through an isotropic porous reinforcement material. However, recent efforts are beginning to account for the multiscale and multidisciplinary complexity of woven materials, in simulations that can provide greater fidelity. In particular, new multi-physics process models are able to better predict the infusion behavior through textiles by considering the effect of fabric deformation on permeability and porosity properties within the reinforcing material. In addition to reviewing previous research related to process modeling and the current state of the art, this paper highlights the recent validation of a multi-physics process model against the experimental infusion of a complex double dome component. By accounting for deformation-dependent flow behavior, the multi-physics process model was able to predict realistic flow behavior, demonstrating considerable improvement over basic isotropic permeability models.

Beyond high resolving power, electron microscopy can be used to study both the electronic and magnetic properties of a sample. Here, Grillo et al. combine electron vortex beams with holographic detection to measure out-of-plane nanoscale magnetic fields.