bluuebunny/crossref_metadata_2025 huggingface dataset:
The Differential Effects of Knowledge on Perceptions of Genetically Modified Food Safety
Authors: Hasell Ariel , Stroud Natalie Jomini
Published: July 2019

Despite scientific consensus in the US that genetically modified (GM) foods are generally as safe as conventionally grown foods, the public remains skeptical about their safety. Extant research shows mixed results about the relationship between knowledge and attitudes when it comes to public opinion of GM foods in the US. This study uses data from the Pew American Trends Panel to examine the relationship between knowledge about GM foods and beliefs about their safety, in addition to what may be moderating these relationships. Results show that the relationship between knowledge and belief varies across different types of knowledge and that the effect of knowledge is moderated by perceptions of the immorality of genetic modification, rather than political or religious views.
Saliva Real-Time Polymerase Chain Reaction for Targeted Screening of Congenital Cytomegalovirus Infection
Authors: Eventov-Friedman Smadar , Manor Hili , Bar-Oz Benjamin , Averbuch Diana , Caplan Orit , Lifshitz Aliza , Bdolah-Abram Tali , Wolf Dana G
Published: July 2019

Background

Saliva real-time polymerase chain reaction (PCR) was shown to be sensitive and specific for the detection of congenital cytomegalovirus (cCMV) in universal screening studies. In the current study, we assessed the performance of saliva real-time PCR in newborns undergoing targeted cCMV screening.

Methods

Saliva real-time PCR results were prospectively correlated with reference-standard urine detection in newborns undergoing targeted cCMV screening over a 3-year period, in successive validation (concurrent testing of all saliva and urine specimens) and routine-screening (confirmatory urine testing of positive saliva results) implementation phases.

Results

The sensitivity, specificity, and positive and negative predictive values of saliva real-time PCR were 98.3% (95% confidence interval, 90.8%–99.9%), 91.5% (89.3%–93.3%), 45.6% (36.7%–54.7%), and 99.9% (99.2%–99.9%), respectively, in 856 concurrently tested newborns. True-positive saliva real-time PCR detection (defined in relation to urine detection) was associated with earlier saliva sampling (P = .002) and a higher saliva viral load (P < .001). We further identified a saliva viral load cutoff value that reliably distinguished between true-positive and false-positive saliva results.

Conclusions

In newborns undergoing targeted screening for cCMV, saliva real-time PCR is highly sensitive yet has a low positive predictive value, necessitating confirmatory testing. Early sampling and application of a validated viral load cutoff could improve the assay performance and support its large-scale implementation in this growing clinical setting.
Effect of default order set settings on telemetry ordering
Authors: Rubins David , Boxer Robert , Landman Adam , Wright Adam
Published: July 2019

Objective

To investigate the effects of adjusting the default order set settings on telemetry usage.

Materials and Methods

We performed a retrospective, controlled, before-after study of patients admitted to a house staff medicine service at an academic medical center examining the effect of changing whether the admission telemetry order was pre-selected or not. Telemetry orders on admission and subsequent orders for telemetry were monitored pre- and post-change. Two other order sets that had no change in their default settings were used as controls.

Results

Between January 1, 2017 and May 1, 2018, there were 1, 163 patients admitted using the residency-customized version of the admission order set which initially had telemetry pre-selected. In this group of patients, there was a significant decrease in telemetry ordering in the post-intervention period: from 79.1% of patients in the 8.5 months prior ordered to have telemetry to 21.3% of patients ordered in the 7.5 months after (χ2 = 382; P < .001). There was no significant change in telemetry usage among patients admitted using the two control order sets.

Discussion

Default settings have been shown to affect clinician ordering behavior in multiple domains. Consistent with prior findings, our study shows that changing the order set settings can significantly affect ordering practices. Our study was limited in that we were unable to determine if the change in ordering behavior had significant impact on patient care or safety.

Conclusion

Decisions about default selections in electronic health record order sets can have significant consequences on ordering behavior.
Technical note: concentrations of soluble, insoluble, and total dietary fiber in feed ingredients determined using Method AOAC 991.43 are not different from values determined using Method AOAC 2011.43 with the AnkomTDF Dietary Fiber Analyzer
Authors: Nguyen Nga , Jacobs Marc , Li Juntao , Huang Chengfei , Li Defa , Navarro Diego M D L , Stein Hans H , Jaworski Neil W
Published: July 2019

The primary objective of this experiment was to test the hypothesis that concentrations of soluble (SDF), insoluble (IDF), and total dietary fiber (TDF) in feed ingredients used in diets for pigs and poultry analyzed using Method AOAC 2011.25 are greater than values determined using Method AOAC 991.43. A second objective was to determine the variation that may exist among 3 laboratories using the 2 methods with the AnkomTDF Dietary Fiber Analyzer (Ankom Technology, Macedon, NY). The 3 laboratories were the Ministry of Agriculture Feed Industry Center (MAFIC) at China Agricultural University, Trouw Nutrition, and Hans H. Stein Monogastric Nutrition Laboratory at University of Illinois at Urbana-Champaign (UIUC). All laboratories analyzed SDF and IDF in feed ingredients in duplicate or triplicate using both methods AOAC 991.43 and 2011.25 with the AnkomTDF Dietary Fiber Analyzer. The 9 test ingredients were wheat, soybean meal, rapeseed meal, sugar beet pulp, peas, horse beans, native pea starch, and 2 samples of corn; 1 from Europe and 1 from China. All ingredient samples, with the exception of Chinese corn, were procured by Trouw Nutrition, ground to pass through a 0.5 mm screen, subsampled, and sent to MAFIC and UIUC. Data were analyzed using SDF, IDF, and TDF as response variables, replication as random effect, and method and location as fixed effects over all ingredients and within each ingredient. When averaged among 9 different ingredients, results indicated that SDF, IDF, and TDF values were not different with either method or at any laboratory. However, the concentration of IDF in corn, wheat, peas, and sugar beet pulp determined using Method AOAC 991.43 was greater (P < 0.05) compared with 2011.25. Soluble dietary fiber determined using Method AOAC 2011.25 was greater (P < 0.05) in corn, rapeseed meal, soybean meal, and sugar beet pulp compared with 991.43. There was no difference in TDF determined with either method, except for wheat having greater (P < 0.05) TDF when determined using Method AOAC 991.43. Interlaboratory variation for SDF, IDF, and TDF was 0.38, 0.87, 1.20, respectively, with Method AOAC 991.43 and 0.40, 0.93, and 1.27, respectively, with 2011.25. Therefore, values determined with the AnkomTDF Analyzer are repeatable among laboratories and can be used in feed formulation worldwide. In conclusion, it is recommended that Method AOAC 991.43 be used to determine SDF, IDF, and TDF in feed ingredients and diets for pigs and poultry.
Effects of Bariatric Surgery Observed in Postmortem Toxicology Casework
Authors: Bishop-Freeman Sandra C , Skirnick Olivia , Noble Chelsea N , Eagerton David H , Winecker Ruth E
Published: July 2019

Bariatric surgery has been on the rise and patients often have multiple indications for pre- and post-operative pharmacotherapy. Procedures target the stomach and/or small intestine and affect weight loss through restriction, malabsorption, or a combination of the two. The absorption and/or metabolism of drugs via the gastrointestinal tract could be altered by different mechanisms. Several cases at the North Carolina Office of the Chief Medical Examiner’s Toxicology Laboratory (NCOCME) have raised questions about the potential impact of these procedures on the disposition of drugs in the body and how that altered disposition may affect cause and manner of death. Overmedication and postmortem redistribution are not enough to explain the phenomena seen in some NCOCME bariatric surgery-related casework. Case examples include a 46-year-old female with a history of Roux-en-Y gastric bypass (RYGB) who suffered a witnessed collapse. Toxicological findings included elevated concentrations of oxymorphone at 0.49 mg/L in vena cava blood. A 67-year-old female, who died from vomiting and bacterial gastritis one day after placement of two intragastric weight-loss balloons, had elevated concentrations of duloxetine at 1.4 mg/L in the iliac vein blood and 9.3 mg/kg in the liver. Her medication was strictly controlled by her sister and gastric contents were without intact tablets or residue at autopsy.
In ovaries with high or low variation in follicle size, granulosa cells of antral follicles exhibit distinct size-related processes
Authors: Costermans N G J , Keijer J , van Schothorst E M , Kemp B , Keshtkar S , Bunschoten A , Soede N M , Teerds K J
Published: July 2019

Antral follicle size might be a valuable additive predictive marker for IVF outcome. To better understand consequences of antral follicle size as a marker for reproductive outcome, we aimed to obtain insight in follicle size-related granulosa cell processes, as granulosa cells play an essential role in follicular development via the production of growth factors, steroids and metabolic intermediates. Using the pig as a model, we compared gene expression in granulosa cells of smaller and larger follicles in the healthy antral follicle pool of sows, which had a high variation versus low variation in follicle size. Selected gene expression was confirmed at the protein level. Granulosa cells of smaller antral follicles showed increased cell proliferation, which was accompanied by a metabolic shift towards aerobic glycolysis (i.e. the Warburg effect), similar to other highly proliferating cells. High granulosa cell proliferation rates in smaller follicles might be regulated via increased granulosa cell expression of the androgen receptor and the epidermal growth factor receptor, which are activated in response to locally produced mitogens. While granulosa cells of smaller follicles in the pool are more proliferative, granulosa cells of larger follicles express more maturation markers such as insulin-like growth factor-1 (IGF1) and angiopoietin 1 (ANGPT1) and are therefore more differentiated. As both higher IGF1 and ANGPT1 have been associated with better IVF outcomes, the results of our study imply that including smaller follicles for oocyte aspiration might have negative consequences for IVF outcome.
Infrared nanospectroscopic mapping of a single metaphase chromosome
Authors: Lipiec Ewelina , Ruggeri Francesco S , Benadiba Carine , Borkowska Anna M , Kobierski Jan D , Miszczyk Justyna , Wood Bayden R , Deacon Glen B , Kulik Andrzej , Dietler Giovanni , Kwiatek Wojciech M
Published: July 2019

The integrity of the chromatin structure is essential to every process occurring within eukaryotic nuclei. However, there are no reliable tools to decipher the molecular composition of metaphase chromosomes. Here, we have applied infrared nanospectroscopy (AFM-IR) to demonstrate molecular difference between eu- and heterochromatin and generate infrared maps of single metaphase chromosomes revealing detailed information on their molecular composition, with nanometric lateral spatial resolution. AFM-IR coupled with principal component analysis has confirmed that chromosome areas containing euchromatin and heterochromatin are distinguishable based on differences in the degree of methylation. AFM-IR distribution of eu- and heterochromatin was compared to standard fluorescent staining. We demonstrate the ability of our methodology to locate spatially the presence of anticancer drug sites in metaphase chromosomes and cellular nuclei. We show that the anticancer 'rule breaker' platinum compound [Pt[N(p-HC6F4)CH2]2py2] preferentially binds to heterochromatin, forming localized discrete foci due to condensation of DNA interacting with the drug. Given the importance of DNA methylation in the development of nearly all types of cancer, there is potential for infrared nanospectroscopy to be used to detect gene expression/suppression sites in the whole genome and to become an early screening tool for malignancy.
Silicosis in rhinestone-manufacturing workers in South China
Authors: Wen C , Wen X , Li R , Su S , Xu H
Published: July 2019

Background

Silicosis is caused by long-term exposure to silica dust. Crystal rhinestone workers can be exposed to high levels of silica dust and are at risk of silicosis.

Aims

To explore silicosis cases, silica dust exposure and control measures in a rhinestone factory in South China.

Methods

We extracted and analysed data on new silicosis cases reported to China’s occupational disease and occupational health information monitoring system between 2006 and 2012 from a rhinestone factory in South China. We measured the quartz content of bulk dust, static total and respirable dust samples.

Results

Ninety-eight silicosis cases were reported between 2006 and 2012. The mean duration of silica dust exposure was 9.2 years (range 3–16). Drilling and polishing workers accounted for 96 (98%) of cases. We collected 1479 static samples including 690 total dust and 789 respirable dust samples. Mean dust levels for drilling were 1.01 mg/m3 (range 0.20–3.80) for total dust and 0.51 mg/m3 (range 0.04–1.70) for respirable dust. Mean dust levels for polishing were 0.59 mg/m3 (range 0.20–2.10) for total dust and 0.28 mg/m3 (range 0.08–0.71) for respirable dust. Over a third [289/789 (37%)] of total dust samples and 129/690 (19%) respirable dust samples exceeded the national permissible exposure limit.

Conclusion

Exposure to silica dust, ineffective dust control measures and inefficient health surveillance may have contributed to the incidence of silicosis in the factory we studied. Identification of silica dust exposure and effective dust control measures would reduce the risk of silicosis in rhinestone workers.
Resection of Cavernous Sinus Meningioma via Lateral Orbitotomy Approach: 2-Dimensional Operative Video
Authors: Cohen Michael A , Couldwell William T
Published: July 2019

Cavernous sinus meningiomas are rare benign tumors arising from the dural wall of the cavernous sinus. These complex lesions are difficult to access surgically but can lead to cranial nerve palsies if left untreated. The case described in this video involved a 14-yr-old girl who presented initially with right ocular pain at 9 yr old. Strabismus of the right eye developed when she was 10 yr old; it was treated surgically without improvement. She developed ptosis and worsening strabismus at age 13 yr, at which time magnetic resonance imaging revealed a lesion in the anterior cavernous sinus and superior orbital fissure. Given the progressively worsening oculomotor palsy and potential for future tumor growth because of her young age, the patient's family wished to pursue surgical rather than radiation treatment. The patient underwent a right lateral orbitotomy for exploration and resection of the lesion. She tolerated the procedure well. Postoperatively, she experienced improvement in her ocular pain and persistent oculomotor nerve palsy without any new neurologic deficits. Her cosmetic results from this incision were satisfactory. Postoperative computed tomography demonstrated thinning of the right lateral orbital wall and removal of the tumor. The pathological analysis of the tissue was consistent with a grade 1 meningioma. This video demonstrates the opportunity to resect a lesion from the cavernous sinus that prevents progressive cranial neuropathies. Some cavernous meningiomas are well circumscribed and can be resected totally. The patient's parents provided consent for publication.
The Legality of Prisoner of War Labour In England, 1648–1655*
Authors: Tycko Sonia
Published: July 2019

Prisoners of war formed a legally distinct category amongst the many thousands of people forcibly employed in England and the English American colonies in the mid-seventeenth century, but they have yet to be studied as such. Focusing on 1648 to 1655, this article explains how a succession of English governments sent their war captives into servitude with private masters despite the prohibition of hard labour for Christian prisoners in the customary laws of war. They instead operated under the logic of the English poor law, in which the indigent could meaningfully consent to serve a master even while under duress. The case of Scottish and Dutch prisoners of war in the Bedford Level fen drainage project shows how the Council of State and the drainage company board members conceptualized common prisoners as willing workmen. Prisoners, ambassadors, and a variety of English observers instead thought that war captives should not have to work for their subsistence or their captors' profit. Nevertheless, common prisoners continued to labour under the aegis of free contracts into the eighteenth century.
Generation of the Mt Kinabalu Granite by Crustal Contamination of Intraplate Magma Modelled by Equilibrated Major Element Assimilation with Fractional Crystallization (EME-AFC)
Authors: Burton-Johnson A , Macpherson C G , Ottley C J , Nowell G M , Boyce A J
Published: July 2019

New geochemical data are presented for the composite units of the Mount Kinabalu granitoid intrusion of Borneo and utilised to explore the discrimination between crustal- and mantle-derived granitic magmas. The geochemical data demonstrate that the units making up this composite intrusion became more potassic through time. This was accompanied by an evolution of isotope ratios from a continental-affinity towards a slightly more mantle-affinity (87Sr/86Sri ∼0·7078; 143Nd/144Ndi ∼0·51245; 206Pb/204Pbi ∼18·756 for the oldest unit compared to 87Sr/86Sri ∼0·7065, 143Nd/144Ndi ∼0·51250 and 206Pb/204Pbi ∼18·721 for the younger units). Oxygen isotope ratios (calculated whole-rock δ18O of +6·5–9·3‰) do not show a clear trend with time. The isotopic data indicate that the magma cannot result only from fractional crystallization of a mantle-derived magma. Alkali metal compositions show that crustal anatexis is also an unsuitable process for genesis of the intrusion. The data indicate that the high-K units were generated by fractional crystallization of a primary, mafic magma, followed by assimilation of the partially melted sedimentary overburden. We present a new, Equilibrated Major Element -Assimilation with Fractional Crystallization (EME-AFC) approach for simultaneously modelling the major element, trace element, and radiogenic and oxygen isotope compositions during such magmatic differentiation; addressing the lack of current AFC modelling approaches for felsic, amphibole- or biotite-bearing systems. We propose that Mt Kinabalu was generated through low degree melting of upwelling fertile metasomatized mantle driven by regional crustal extension in the Late Miocene.
Improving folding properties of computationally designed proteins
Authors: Bjerre Benjamin , Nissen Jakob , Madsen Mikkel , Fahrig-Kamarauskaitė Jūratė , Norrild Rasmus K , Holm Peter C , Nordentoft Mathilde K , O’Shea Charlotte , Willemoës Martin , Johansson Kristoffer E , Winther Jakob R
Published: July 2019

While the field of computational protein design has witnessed amazing progression in recent years, folding properties still constitute a significant barrier towards designing new and larger proteins. In order to assess and improve folding properties of designed proteins, we have developed a genetics-based folding assay and selection system based on the essential enzyme, orotate phosphoribosyl transferase from Escherichia coli. This system allows for both screening of candidate designs with good folding properties and genetic selection of improved designs. Thus, we identified single amino acid substitutions in two failed designs that rescued poorly folding and unstable proteins. Furthermore, when these substitutions were transferred into a well-structured design featuring a complex folding profile, the resulting protein exhibited native-like cooperative folding with significantly improved stability. In protein design, a single amino acid can make the difference between folding and misfolding, and this approach provides a useful new platform to identify and improve candidate designs.
Bank Deposits and the Stock Market
Authors: Lin Leming
Published: July 2019

I show that households’ demand for retail deposits decreases during stock market booms, which induces a contraction in bank lending and a decrease in real activity in bank-dependent firms. I identify this channel using geographic heterogeneity in households’ stock market participation. Banks in areas with greater stock ownership see a greater reduction in deposit growth when stock returns are high. This holds even across branches of the same bank and across ZIP codes within counties. Counties served by banks financed by more stock-active depositors see a greater decline in bank lending and bank-dependent-firm employment following high stock returns.
Corporate Governance and Pollution Externalities of Public and Private Firms*
Authors: Shive Sophie A , Forster Margaret M
Published: July 2019

The number of U.S. publicly traded firms has halved in 20 years. How will this shift in ownership structure affect the economy’s externalities? Using comprehensive data on greenhouse gas emissions from 2007 to 2016, we find that independent private firms are less likely to pollute and incur EPA penalties than are public firms, and we find no differences between private sponsor-backed firms and public firms, controlling for industry, time, location, and a host of firm characteristics. Within public firms, we find a negative association between emissions and mutual fund ownership and board size, suggesting that increased oversight may decrease externalities.
Geo-epidemiology and socioeconomic aspects of human sporotrichosis in the municipality of Duque de Caxias, Rio de Janeiro, Brazil, between 2007 and 2016
Authors: Alzuguir Claudia L C , Pereira Sandro A , Magalhães Mônica A F M , Almeida-Paes Rodrigo , Freitas Dayvison F S , Oliveira Liliane F A , Pimentel Maria Inês F
Published: July 2019

Background

Sporotrichosis is usually caused by the traumatic inoculation of pathogenic species of fungi of the genus Sporothrix. The most prevalent species in Brazil is Sporothrix brasiliensis, which is generally associated with transmission involving infected cats. Sporotrichosis is hyperendemic in the state of Rio de Janeiro and Duque de Caxias is one of the most affected municipalities.

Methods

This was a cross-sectional, geo-epidemiological and socioeconomic study of human sporotrichosis in the municipality of Duque de Caxias using geoprocessing information for the construction of thematic maps.

Results

Eight hundred and twenty-seven cases of sporotrichosis from Duque de Caxias were reported between 2007 and 2016, most of them in women from 25-59 years. The most affected areas had low per capita income and scarce supply of treated water. Human sporotrichosis expanded throughout the territory of the municipality over time.

Conclusions

An increase in both the number of reported cases and their spatial distribution occurred throughout the studied decade. The concentration of the disease was more intense in areas with greater vulnerability of the population, expressed by low per capita income and deficient provision of basic sanitation services. Sporotrichosis requires measures to better control the disease in Duque de Caxias and in the state of Rio de Janeiro.
Sitagliptin decreases visceral fat and blood glucoses in women with polycystic ovarian syndrome
Authors: Devin Jessica K. , Nian Hui , Celedonio Jorge E. , Wright Patricia , Brown Nancy J.
Published: July 2019

Context

Women with polycystic ovarian syndrome (PCOS) have decreased growth hormone (GH), which can increase visceral adiposity (VAT) and impair vascular function. GH releasing hormone, a dipeptidyl peptidase-4 (DPP4) substrate, stimulates GH secretion.

Objective

We tested the hypothesis that DPP4 inhibition increases GH and improves glucose levels and vascular function in women with PCOS.

Methods

Eighteen women with PCOS participated in a double-blinded, cross-over study. They received sitagliptin 100 mg vs. placebo daily for one month separated by an eight-week washout. During each treatment, women underwent a 75-gram oral glucose tolerance test (OGTT), assessment of vascular function and body composition. Overnight GH secretion was assessed via venous sampling every 10 minutes for 12 hours and analyzed using an automated deconvolution algorithm.

Results

During OGTT, sitagliptin increased GLP-1 (p<0.001), early insulin secretion (from mean insulinogenic index 1.9±1.2 (SD) to 3.2±3.1; p=0.02) and decreased peak glucose (mean −17.2 mg/dL [95% CI −27.7, −6.6]; p<0.01). At one month, sitagliptin decreased VAT (from 1141.9±700.7 to 1055.1±710.1 g; p=0.02) but did not affect vascular function. Sitagliptin increased GH half-life (from 13.9±3.6 to 17.0±6.8 min, N=16; p=0.04) and interpulse interval (from 53.2±20.0 to 77.3±38.2 min, N=16; p<0.05) but did not increase mean overnight GH (p=0.92 vs. placebo).

Conclusions

Sitagliptin decreased the maximal glucose response to OGTT and VAT. Sitagliptin did not increase overnight GH but increased GH half-life and the interpulse interval.

Precis

Sitagliptin improved body composition and blood glucoses following oral glucose load in women with PCOS. Sitagliptin potentiated GH half-life but did not increase overnight GH levels.
Design of a computer model for the identification of adolescent swimmers with low BMD
Authors: Marin-Puyalto Jorge , Gomez-Cabello Alba , Gomez-Bruton Alejandro , Matute-Llorente Angel , Gonzalez-Aguero Alejandro , Casajus Jose Antonio , Vicente-Rodriguez German
Published: July 2019

Objectives

This paper aims to elaborate a decision tree for the early detection of adolescent swimmers at risk of presenting low bone mineral density (BMD), based on easily measurable fitness and performance variables.

Methods

Bone mineral status of 78 adolescent swimmers was determined using DXA scans at the hip and subtotal body. Participants also underwent physical fitness (upper and lower body strength, running speed and cardiovascular endurance) and performance (swimming history, speed and ranking) assessments. A gradient boosting machine regression tree was built in order to predict BMD of the swimmers and to further develop a simpler individual decision tree, using a subtotal BMD height-adjusted Z-score of −1 as threshold value.

Results

The predicted BMD using the gradient boosted model was strongly correlated with the actual BMD values obtained from DXA (r=0.960, p<0.0001) with a root mean squared error of 0.034 g/cm2. According to a simple decision tree, that showed a 73.9% of classification accuracy, swimmers with a body mass index (BMI) lower than 17 kg/m2 or a handgrip strength inferior to 43kg with the sum of both arms could be at higher risk of having low BMD.

Conclusion

Easily measurable fitness variables (BMI and handgrip strength) could be used for the early detection of adolescent swimmers at risk of suffering from low BMD. The presented decision tree could be used in training settings to determine the necessity of further BMD assessments.

Summary box

What are the new findings?

Adolescent swimmers with a low BMI or handgrip strength seem more likely to be at higher risk of having low BMD.

Subtotal BMD values predicted from our regression model are strongly correlated with DXA measurements.

How might it impact on clinical practice in the future

Healthcare professionals could easily detect adolescent swimmers in need of a DXA scan.

The computer-based regression tree could be included in low BMD management and screening strategies.
Childhood immune imprinting to influenza A shapes birth year-specific risk during seasonal H1N1 and H3N2 epidemics
Authors: Gostic Katelyn M , Bridge Rebecca , Brady Shane , Viboud Cécile , Worobey Michael , Lloyd-Smith James O
Published: July 2019

Across decades of co-circulation in humans, influenza A subtypes H1N1 and H3N2 have caused seasonal epidemics characterized by different age distributions of infection and mortality. H3N2 causes the majority of cases in high-risk elderly cohorts, and the majority of overall deaths, whereas H1N1 causes incidence shifted towards young and middle-aged adults, and fewer deaths. These contrasting age profiles may result from differences in childhood exposure to H1N1 and H3N2 or from differences in evolutionary rate between subtypes. Here we analyze a large epidemiological surveillance dataset to test whether childhood immune imprinting shapes seasonal influenza epidemiology, and if so, whether it acts primarily via immune memory of a particular influenza subtype or via broader immune memory that protects across subtypes. We also test the impact of evolutionary differences between influenza subtypes on age distributions of infection. Likelihood-based model comparison shows that narrow, within-subtype imprinting is the strongest driver of seasonal influenza risk. The data do not support a strong effect of evolutionary rate, or of broadly protective imprinting that acts across subtypes. Our findings emphasize that childhood exposures can imprint a lifelong immunological bias toward particular influenza subtypes, and that these cohort-specific biases shape epidemic age distributions. As a result, newer and less “senior” antibody responses acquired later in life do not provide the same strength of protection as responses imprinted in childhood. Finally, we project that the relatively low mortality burden of H1N1 may increase in the coming decades, as cohorts that lack H1N1-specific imprinting eventually reach old age.
Effects of vitamin D supplementation and seasonality on circulating cytokines in adolescents: analysis of data from a feasibility trial in Mongolia
Authors: Yegorov Sergey , Bromage Sabri , Boldbaatar Ninjin , Ganmaa Davaasambuu
Published: July 2019

Vitamin D deficiency is prevalent in human populations and has been linked to immune dysfunction. Here we explored the effects of cholecalciferol supplementation on circulating cytokines in severely vitamin D deficient (blood 25(OH)D3 << 30 nmol/L) adolescents aged 12-15 from Mongolia. The study included 28 children receiving 800 IU daily cholecalciferol for 6 months spanning winter and spring, and 30 children receiving placebo during the same period. The levels of 25(OH)D3 were assessed at baseline, three and six months. Twenty-one cytokines were measured in serum at baseline and at six months. The median blood 25(OH)D3 concentration at baseline was 13.7 nmol/L (IQR=10.0-21.7). Supplementation tripled blood 25(OH)D3 levels (p<0.001) and reversed the direction of change for most cytokines (16/21, 86%). Supplementation was associated with elevated interleukin (IL)-6 (p=0.043). The placebo group had reduced MIP-1α (p=0.007) and IL-8 (p=0.034) at six months. These findings suggest that cholecalciferol supplementation and seasonality have a measurable impact on circulating cytokines in adolescents, identifying chemokines as potentially important biomarkers of vitamin D status in this population.

ClinicalTrial.org ID:NCT01244204
Earliest infections predict the age distribution of seasonal influenza A cases
Authors: Arevalo Philip , McLean Huong Q. , Belongia Edward A. , Cobey Sarah
Published: July 2019

Seasonal variation in the age distribution of influenza A cases suggests that factors other than age shape susceptibility to medically attended infection. We ask whether these differences can be partly explained by protection conferred by childhood influenza infection, which has lasting impacts on immune responses to influenza and protection against new influenza A subtypes (phenomena known as original antigenic sin and immune imprinting). Fitting a statistical model to data from studies of influenza vaccine effectiveness (VE), we find that primary infection appears to reduce the risk of medically attended infection with that subtype throughout life. This effect is stronger for H1N1 compared to H3N2. Additionally, we find evidence that VE varies with both age and birth year, suggesting that VE is sensitive to early exposures. Our findings may improve estimates of age-specific risk and VE in similarly vaccinated populations and thus improve forecasting and vaccination strategies to combat seasonal influenza.
Mediterranean Diet and atherothrombosis biomarkers: a randomized controlled trial
Authors: Hernáez Álvaro , Castañer Olga , Tresserra-Rimbau Anna , Pintó Xavier , Fitó Montserrat , Casas Rosa , Martínez-González Miguel Ángel , Corella Dolores , Salas-Salvadó Jordi , Lapetra José , Gómez-Gracia Enrique , Arós Fernando , Fiol Miquel , Serra-Majem Lluis , Ros Emilio , Estruch Ramón
Published: July 2019

Scope

To assess whether following a Mediterranean diet (MedDiet) improves atherothrombosis biomarkers in high cardiovascular risk individuals.

Methods and results

In 358 random volunteers from the PREDIMED trial (Prevención con Dieta Mediterránea), we assessed the 1-year effects on atherothrombosis markers of an intervention with MedDiet, enriched with virgin olive oil (MedDiet-VOO;N=120) or nuts (MedDiet-Nuts;N=119) versus a low-fat control diet (N=119). In a secondary, observational approach, we studied whether volunteers with large increments in MedDiet adherence (>2 score points) were associated with 1-year improvements in biomarkers (relative to those worsening their adherence). The MedDiet-VOO intervention increased platelet activating factor-acetylhydrolase activity in high-density lipoproteins (HDLs) by 7.5% [95% confidence interval: 0.17; 14.8] and decreased HDL-bound α1-antitrypsin levels by 6.1% [−11.8; −0.29]. The MedDiet-Nuts one reduced non-esterified fatty acid concentrations by 9.3% [−18.1; −0.53]. Only the low-fat diet was associated with increases in platelet factor-4 and prothrombin factor1+2levels versus baseline (P=0.012 andP=0.003, respectively, according to Wilcoxon signed-rank tests). Finally, large MedDiet increments were associated with less fibrinogen (−9.5% [−18.3; −0.60]) and non-esterified fatty acid concentrations (−16.7% [−31.7; −1.74]).

Conclusion

Following a MedDiet improves atherothrombosis biomarkers in high cardiovascular risk individuals.
Reproducibility and transparency characteristics of oncology research evidence
Authors: Walters Corbin G , Harter Zachery J , Wayant Cole , Vo Nam , Warren Michael , Chronister Justin , Tritz Daniel , Vassar Matt
Published: July 2019

Introduction

As much as 50%-90% of research is estimated to be irreproducible, costing upwards of $28 billion in the United States alone. Reproducible research practices are essential to improving the reproducibility and transparency of biomedical research, such as including pre-registering studies, publishing a protocol, making research data and metadata publicly available, and publishing in open access journals. Here we report an investigation of key reproducible or transparent research practices in the published oncology literature.

Methods

We performed a cross-sectional analysis of a random sample of 300 oncology studies published from 2014-2018. We extracted key reproducibility and transparency characteristics in a duplicative fashion by blinded investigators using a pilot tested Google Form.

Results

Of the 300 studies randomly sampled, 296 studies were analyzed for study reproducibility characteristics. Of these 296 studies, 194 were contained empirical data that could be analyzed for reproducible and transparent research practices. Raw data was available for 9 studies (4.6%). Approximately 5 studies (2.6%) provided a protocol. Despite our sample including 15 clinical trials and 7 systematic reviews/meta-analyses, only 7 included a pre-registration statement. Less than 25% (65/194) of studies provided an author conflict of interest statement.

Discussion

We found that key reproducibility and transparency characteristics were absent from a random sample of published oncology studies. We recommend required pre-registration for all eligible trials and systematic reviews, published protocols for all manuscripts, and deposition of raw data and metadata in public repositories.
Redefining typhoid diagnosis: what would an improved test need to look like?
Authors: Mather Richard , Hopkins Heidi , Parry Christopher M. , Dittrich Sabine
Published: July 2019

Introduction

Typhoid fever is one of the most common bacterial causes of acute febrile illness in the developing world, with an estimated 10.9 million new cases and 116.8 thousand deaths in 2017. Typhoid point-of-care (POC) diagnostic tests are widely used but have poor sensitivity and specificity, resulting in antibiotic overuse that has led to the emergence and spread of multidrug resistant strains. With recent advances in typhoid surveillance and detection, this is the ideal time to produce a target product profile (TPP) that guides product development and ensure that a next-generation test meets the needs of users in the resource-limited settings where typhoid is endemic.

Methods

A structured literature review was conducted to develop a draft TPP for a next-generation typhoid diagnostic test with minimal and optimal desired characteristics for 36 test parameters. The TPP was refined using feedback collected from a Delphi survey of key stakeholders in clinical medicine, microbiology, diagnostics and public and global health.

Results

A next-generation typhoid diagnostic test should improve patient management through the diagnosis and treatment of infection with acute Salmonella enterica serovars Typhi or Paratyphi with a sensitivity ≥90% and specificity ≥95%. The test would ideally be used at the lowest level of the healthcare system in settings without a reliable power or water supply and provide results in less than 15 minutes at a cost of <$1.00 USD.

Conclusion

This report outlines the first comprehensive TPP for typhoid fever and is intended to guide the development of a next-generation typhoid diagnostic test. An accurate POC test will reduce the morbidity and mortality of typhoid fever through rapid diagnosis and treatment and will have the greatest impact in reducing antimicrobial resistance if it is combined with diagnostics for other causes of acute febrile illness in a treatment algorithm.
Ethnicity and acculturation: Asian American substance use from early adolescence to mature adulthood
Authors: Ahmmad Zobayer , Adkins Daniel E.
Published: July 2019

Research on Asian American substance use has, to date, been limited by monolithic conceptions of Asian identity, inadequate attention to acculturative process, and a dearth of longitudinal analyses spanning developmental periods. Using five waves of the National Longitudinal Study of Adolescent to Adult Health, this study addresses these limitations by longitudinally investigating disparities in substance use from early adolescence into mature adulthood among Asian American ethnic groups, including subjects identifying as multiple Asian ethnicities and multiracial Asians. The conditional effects of acculturation indicators (e.g., nativity generation, co-ethnic peer networks, co-ethnic neighborhood concentration) on the substance use outcomes were also examined. Results indicate significant variation across Asian ethnicities, with the lowest probabilities of substance use among Chinese and Vietnamese Americans, and the highest among multiracial Asian Americans. Acculturation indicators were also strongly, independently associated with increased substance use, and attenuated many of the observed ethnic disparities, particularly for multiracial, multiethnic, and Japanese Asian Americans. This study argues that ignoring the diversity of Asian ethnicities masks the presence of high-risk Asian American groups. Moreover, results indicate that, among Asian Americans, substance use is strongly positively associated with acculturation to U.S. cultural norms, and generally peaks at later ages than the U.S. average.
Deficient goal-directed control in a population characterized by extreme goal pursuit
Authors: Foerde Karin , Daw Nathaniel D. , Rufin Teresa , Walsh B Timothy , Shohamy Daphna , Steinglass Joanna E.
Published: July 2019

Abstract

Computational neuroscience has contributed to understanding compulsive behavior by distinguishing habitual from goal-directed choice through model-free and model-based learning. Yet, questions remain about applying this approach to psychiatric conditions that are characterized by complex behaviors that occur outside the laboratory. Here, we compared individuals with anorexia nervosa (AN), whose self-starvation appears both excessively goal-directed and habitual, with healthy controls (HC) to assess: 1) whether their behavior is characterized by enhanced or diminished model-based behavior, 2) the domain specificity of any abnormalities by comparing learning in a food-specific context as well as in a monetary context, and 3) whether impairments are secondary to starvation by comparing learning before and after initial treatment. Across all conditions, individuals with AN showed an impairment in model-based, but not model-free, learning, suggesting a general and persistent contribution of habitual over goal-directed control, across domains and timepoints.
Horse gluteus is a null-sarcolipin muscle with enhanced sarcoplasmic reticulum calcium transport
Authors: Autry Joseph M. , Karim Christine B. , Svensson Bengt , Carlson Samuel F. , Cocco Mariana , Perumbakkam Sudeep , Chen Zhenhui , Espinoza-Fonseca L. Michel , Finno Carrie J. , Thomas David D. , Valberg Stephanie J.
Published: July 2019

We have analyzed gene transcription, protein expression, and enzymatic activity of the Ca2+-transporting ATPase (SERCA) in horse gluteal muscle. Horses are bred for peak athletic performance but exhibit a high incidence of exertional rhabdomyolysis, with myosolic Ca2+suggested as a correlative linkage. To assess Ca2+regulation in horse gluteus, we developed an improved protocol for isolating horse sarcoplasmic reticulum (SR) vesicles. RNA-seq and immunoblotting determined that theATP2A1gene (protein product SERCA1) is the predominant Ca2+-ATPase expressed in horse gluteus, as in rabbit muscle. Gene expression was assessed for four regulatory peptides of SERCA, finding that sarcolipin (SLN) is the predominant regulatory peptide transcript expressed in horse gluteus, as in rabbit muscle. Surprisingly, the RNA transcription ratio ofSLN-to-ATP2A1in horse gluteus is an order of magnitude higher than in rabbit muscle, but conversely, the protein expression ratio of SLN-to-SERCA1 in horse gluteus is an order of magnitude lower than in rabbit. Thus, theSLNgene is not translated to a stable protein in horse gluteus, yet the supra-high level ofSLNRNA suggests a non-coding role. Gel-stain analysis revealed that horse SR expresses calsequestrin (CASQ) protein abundantly, with a CASQ-to-SERCA ratio ∼3-fold greater than rabbit SR. The Ca2+transport rate of horse SR vesicles is ∼2-fold greater than rabbit SR, suggesting horse myocytes have enhanced luminal Ca2+stores that increase intracellular Ca2+release and muscular performance. The absence of SLN inhibition of SERCA and the abundant expression of CASQ may potentiate horse muscle contractility and susceptibility to exertional rhabdomyolysis.
Automated osteosclerosis grading of clinical biopsies using infrared spectroscopic imaging
Authors: Mankar Rupali , Bueso-Ramos Carlos E. , Yin C. Cameron , Hidalgo-Lopez Juliana E. , Berisha Sebastian , Kansiz Mustafa , Mayerich David
Published: July 2019

Osteosclerosis and myefibrosis are complications of myeloproliferative neoplasms. These disorders result in excess growth of trabecular bone and collagen fibers that replace hematopoietic cells, resulting in abnormal bone marrow function. Treatments using imatinib and JAK2 pathway inhibitors can be effective on osteosclerosis and fibrosis, therefore accurate grading is critical for tracking treatment effectiveness. Current grading standards use a four-class system based on analysis of biopsies stained with three histological stains: hematoxylin and eosin (H&E), Masson’s trichrome, and reticulin. However, conventional grading can be subjective and imprecise, impacting the effectiveness of treatment. In this paper, we demonstrate that mid-infrared spectroscopic imaging may serve as a quantitative diagnostic tool for quantitatively tracking disease progression and response to treatment. The proposed approach is label-free and provides automated quantitative analysis of osteosclerosis and collagen fibrosis.
In situ, fluorescence lifetime-based measurements of cell membrane micromechanics
Authors: Son S , Muddana HS , Huang C , Zhang S , Butler PJ
Published: July 2019

Microscopic in situ measurements of the mechanical properties of lipid bilayers were derived from the mean and variance of the fluorescence lifetime distributions of 1’-dioctadecyl-3,3,3’3’-tetramethylindocarbocyanine perchlorate (DiI). In this method, DiI, incorporated into membranes, acts as a membrane-targeted molecular rotor whose fluorescence lifetime is sensitive to local lipid viscosity. A new model was developed in which changes in area per lipid were derived from the first and second moments of a stretched exponential distribution of fluorescence lifetimes of DiI, which were subsequently used to compute mean area per lipid and its variance, quantities directly related to bilayer compressibility and bending moduli. This method enabled molecular scale assays of surface micromechanics of membrane-bound entities, such as nanoliposomes and human red blood cells.

STATEMENT OF SIGNIFICANCE

Despite the progress in cell deformability studies, and in understanding mechanical properties of purified lipid bilayers, there has not, to date, been a method to measure the mechanics of the lipid bilayer in cells in situ. The current manuscript describes such a method. Using a fluorescent molecular rotor, DiI, embedded in the membrane, along with time resolved fluorescence, we directly measure area per lipid, and its temporal and spatial variance, properties directly related to bilayer mechanical moduli. Such a method will allow investigators to start exploring the relationship between lipid bilayer mechanics and cellular health and disease.
Single Cell Analysis Reveals Partial Reactivation of X-chromosome Instead of Chromosome-wide Dampening in Naïve Human Pluripotent Stem Cells
Authors: Mandal S , Chandel D , Kaur H , Majumdar S , Arava M , Gayen S
Published: July 2019

Recently, a unique form of X-chromosome dosage compensation has been demonstrated in human preimplantation embryos, which happens through the dampening of X-linked gene expression from both X-chromosomes. Subsequently, X-chromosome dampening has also been demonstrated in female human pluripotent stem cells (hPSCs) during the transition from primed to naïve state. However, the existence of dampened X-chromosomes remains controversial in both embryos and hPSCs. Specifically, in preimplantation embryos it has been shown that there is inactivation of X-chromosome instead of dampening. Here, we have performed allelic analysis of X-linked genes at the single cell level in hPSCs and found that there is partial reactivation of the inactive X-chromosome instead of chromosome-wide dampening upon conversion from primed to naïve state. In addition, our analysis suggests that the reduced X-linked gene expression in naïve hPSCs might be the consequence of erasure of active X-chromosome upregulation.