bluuebunny/crossref_metadata_2025 huggingface dataset:
Management of carotid stenosis for primary and secondary prevention of stroke: state-of-the-art 2020: a critical review
Authors: Messas Emmanuel , Goudot Guillaume , Halliday Alison , Sitruk Jonas , Mirault Tristan , Khider Lina , Saldmann Frederic , Mazzolai Lucia , Aboyans Victor
Published: December 2020

Carotid atherosclerotic plaque is encountered frequently in patients at high cardiovascular risk, especially in the elderly. When plaque reaches 50% of carotid lumen, it induces haemodynamically significant carotid stenosis, for which management is currently at a turning point. Improved control of blood pressure, smoking ban campaigns, and the widespread use of statins have reduced the risk of cerebral infarction to <1% per year. However, about 15% of strokes are still secondary to a carotid stenosis, which can potentially be detected by effective imaging techniques. For symptomatic carotid stenosis, current ESC guidelines put a threshold of 70% for formal indication for revascularization. A revascularization should be discussed for symptomatic stenosis over 50% and for asymptomatic carotid stenosis over 60%. This evaluation should be performed by ultrasound as a first-line examination. As a complement, computed tomography angiography (CTA) and/or magnetic resonance angiography are recommended for evaluating the extent and severity of extracranial carotid stenosis. In perspective, new high-risk markers are currently being developed using markers of plaque neovascularization, plaque inflammation, or plaque tissue stiffness. Medical management of patient with carotid stenosis is always warranted and applied to any patient with atheromatous lesions. Best medical therapy is based on cardiovascular risk factors correction, including lifestyle intervention and a pharmacological treatment. It is based on the tri-therapy strategy with antiplatelet, statins, and ACE inhibitors. The indications for carotid endarterectomy (CEA) and carotid artery stenting (CAS) are similar: for symptomatic patients (recent stroke or transient ischaemic attack ) if stenosis >50%; for asymptomatic patients: tight stenosis (>60%) and a perceived high long-term risk of stroke (determined mainly by imaging criteria). Choice of procedure may be influenced by anatomy (high stenosis, difficult CAS or CEA access, incomplete circle of Willis), prior illness or treatment (radiotherapy, other neck surgery), or patient risk (unable to lie flat, poor AHA assessment). In conclusion, neither systematic nor abandoned, the place of carotid revascularization must necessarily be limited to the plaques at highest risk, leaving a large place for optimized medical treatment as first line management. An evaluation of the value of performing endarterectomy on plaques considered to be at high risk is currently underway in the ACTRIS and CREST 2 studies. These studies, along with the next result of ACST-2 trial, will provide us a more precise strategy in case of carotid stenosis.
Atrial fibrillation: villain or bystander in vascular brain injury
Authors: Freedman Ben , Kamel Hooman , Van Gelder Isabelle C , Schnabel Renate B
Published: December 2020

Atrial fibrillation (AF) and stroke are inextricably connected, with classical Virchow pathophysiology explaining thromboembolism through blood stasis in the fibrillating left atrium. This conceptualization has been reinforced by the remarkable efficacy of oral anticoagulant (OAC) for stroke prevention in AF. A number of observations showing that the presence of AF is neither necessary nor sufficient for stroke, cast doubt on the causal role of AF as a villain in vascular brain injury (VBI). The requirement for additional risk factors before AF increases stroke risk; temporal disconnect of AF from a stroke in patients with no AF for months before stroke during continuous ECG monitoring but manifesting AF only after stroke; and increasing recognition of the role of atrial cardiomyopathy and atrial substrate in AF-related stroke, and also stroke without AF, have led to rethinking the pathogenetic model of cardioembolic stroke. This is quite separate from recognition that in AF, shared cardiovascular risk factors can lead both to non-embolic stroke, or emboli from the aorta and carotid arteries. Meanwhile, VBI is now expanded to include dementia and cognitive decline: research is required to see if reduced by OAC. A changed conceptual model with less focus on the arrhythmia, and more on atrial substrate/cardiomyopathy causing VBI both in the presence or absence of AF, is required to allow us to better prevent AF-related VBI. It could direct focus towards prevention of the atrial cardiomyopathy though much work is required to better define this entity before the balance between AF as villain or bystander can be determined.
Infective endocarditis and neurologic events: indications and timing for surgical interventions
Authors: Bonaros Nikolaos , Czerny Martin , Pfausler Bettina , Müller Silvana , Bartel Thomas , Thielmann Matthias , Shehada Sharaf-Eldin , Folliguet Thierry , Obadia Jean-Francois , Holfeld Johannes , Lorusso Roberto , Parolari Alessandro , Müller Ludwig , Grimm Michael , Ruttmann-Ulmer Elfriede
Published: December 2020

A therapeutic dilemma arises when infective endocarditis (IE) is complicated by a neurologic event. Postponement of surgery up to 4 weeks is recommended by the guidelines, however, this negatively impacts outcomes in many patients with an urgent indication for surgery due to uncontrolled infection, disease progression, or haemodynamic deterioration. The current literature is ambiguous regarding the safety of cardiopulmonary bypass in patients with recent neurologic injury. Nevertheless, most publications demonstrate a lower risk for secondary haemorrhagic conversion of uncomplicated ischaemic lesions than the risk for recurrent embolism under antibiotic treatment. Here, we discuss the current literature regarding neurologic stroke complicating IE with an indication for surgery.
Cardiovascular disease risk prediction for people with type 2 diabetes in a population-based cohort and in electronic health record data
Authors: Szymonifka Jackie , Conderino Sarah , Cigolle Christine , Ha Jinkyung , Kabeto Mohammed , Yu Jaehong , Dodson John A , Thorpe Lorna , Blaum Caroline , Zhong Judy
Published: December 2020

Objective

Electronic health records (EHRs) have become a common data source for clinical risk prediction, offering large sample sizes and frequently sampled metrics. There may be notable differences between hospital-based EHR and traditional cohort samples: EHR data often are not population-representative random samples, even for particular diseases, as they tend to be sicker with higher healthcare utilization, while cohort studies often sample healthier subjects who typically are more likely to participate. We investigate heterogeneities between EHR- and cohort-based inferences including incidence rates, risk factor identifications/quantifications, and absolute risks.

Materials and methods

This is a retrospective cohort study of older patients with type 2 diabetes using EHR from New York University Langone Health ambulatory care (NYULH-EHR, years 2009–2017) and from the Health and Retirement Survey (HRS, 1995–2014) to study subsequent cardiovascular disease (CVD) risks. We used the same eligibility criteria, outcome definitions, and demographic covariates/biomarkers in both datasets. We compared subsequent CVD incidence rates, hazard ratios (HRs) of risk factors, and discrimination/calibration performances of CVD risk scores.

Results

The estimated subsequent total CVD incidence rate was 37.5 and 90.6 per 1000 person-years since T2DM onset in HRS and NYULH-EHR respectively. HR estimates were comparable between the datasets for most demographic covariates/biomarkers. Common CVD risk scores underestimated observed total CVD risks in NYULH-EHR.

Discussion and conclusion

EHR-estimated HRs of demographic and major clinical risk factors for CVD were mostly consistent with the estimates from a national cohort, despite high incidences and absolute risks of total CVD outcome in the EHR samples.
Machine learning identifies girls with central precocious puberty based on multisource data
Authors: Pan Liyan , Liu Guangjian , Mao Xiaojian , Liang Huiying
Published: December 2020

Objective

The study aimed to develop simplified diagnostic models for identifying girls with central precocious puberty (CPP), without the expensive and cumbersome gonadotropin-releasing hormone (GnRH) stimulation test, which is the gold standard for CPP diagnosis.

Materials and methods

Female patients who had secondary sexual characteristics before 8 years old and had taken a GnRH analog (GnRHa) stimulation test at a medical center in Guangzhou, China were enrolled. Data from clinical visiting, laboratory tests, and medical image examinations were collected. We first extracted features from unstructured data such as clinical reports and medical images. Then, models based on each single-source data or multisource data were developed with Extreme Gradient Boosting (XGBoost) classifier to classify patients as CPP or non-CPP.

Results

The best performance achieved an area under the curve (AUC) of 0.88 and Youden index of 0.64 in the model based on multisource data. The performance of single-source models based on data from basal laboratory tests and the feature importance of each variable showed that the basal hormone test had the highest diagnostic value for a CPP diagnosis.

Conclusion

We developed three simplified models that use easily accessed clinical data before the GnRH stimulation test to identify girls who are at high risk of CPP. These models are tailored to the needs of patients in different clinical settings. Machine learning technologies and multisource data fusion can help to make a better diagnosis than traditional methods.
Impact of increasing levels of fumonisin on performance, liver toxicity, and tissue histopathology of finishing beef steers
Authors: Jennings Jenny S , Ensley Steve M , Smith Wyatt N , Husz Taylor C , Lawrence Ty E
Published: December 2020

To address the gaps in current scientific knowledge, the objective of the present study was to investigate the impact of fumonisin exposure on feedlot cattle intake and performance. Fifty steers were received (day 0; 361 ± 6.4 kg), housed individually and fed once daily at 0800 hours. All steers were transitioned to a dry-rolled corn-based finishing diet from days 0 to 21 and then were fed the control finishing diet until day 50. Treatment diets were formulated to achieve ≤5 (CON), 15 (15PPM), 30 (30PPM), 60 (60PPM), or 90 ppm (90PPM) of total dietary fumonisin. Steers were fed the fumonisin treatment diets from day 50 until harvest on day 160; individual animal body weights (BW) were measured on days 0, 50, 100, 150, 159, and 160. Liver, kidney, and skeletal muscle tissue samples were collected at harvest for histopathological analyses, and liver samples were further analyzed for sphinganine (SA) and sphingosine (SO) concentration. Animal performance, carcass data, and liver enzyme concentration were analyzed using a mixed model; categorical data were analyzed via nonparametric models. Contrasts were used to test for linear and quadratic responses. Throughout the study, there was no effect of treatment (P > 0.60), or a linear response (P > 0.16) from increasing fumonisin levels, on BW or dry matter intake (DMI). However, CON tended to have a lower average daily gain (ADG) than the fumonisin treatments during the fumonisin treatment period (P = 0.10), and there was a positive linear response (P = 0.02) of ADG to fumonisin during the treatment period. There were no treatment differences in hot carcass weight, dressing percentage, marbling score, ribeye area, or yield grade. There were no effects of treatment on either liver abscesses (P = 0.95) or telangiectasis (P = 0.13). We observed a treatment difference for SA and SA:SO (P < 0.01), as well as a quadratic response (P < 0.02); both SA and SA:SO increased as dietary fumonisin increased. There were no observed differences between treatments for histopathology scores of kidney (P = 0.16), liver (P = 0.25), or skeletal muscle (P = 0.59) tissue. No adverse effects were observed in steers fed increasing dietary levels of fumonisin for 110 d prior to harvest. While elevated liver amino alcohol concentration did occur, negative effects on growth and carcass characters were not observed.
Hygiene management in newborn individually housed dairy calves focusing on housing and feeding practices
Authors: Heinemann Céline , Leubner Caroline D , Hayer Jason J , Steinhoff-Wagner Julia
Published: December 2020

In calf rearing, the first weeks of life are critical and associated with the highest mortality due to enteric and respiratory diseases. A well-implemented hygiene management can help to protect calves’ health preventively by reducing the load of pathogenic bacteria and interrupting infection chains. The aim of this study was to identify deficiencies in hygiene management of individually housed dairy calves by surveying current practice and examining feeding and housing equipment with different hygiene indicators. On 11 farms, different locations in 2 pens or hutches for individual calf rearing prepared for restocking and 2 feeding buckets per farm, including the inner and outer surfaces of artificial teats, were visually scored for cleanliness and sampled with swabs (housing equipment: n = 167; feeding equipment: n = 120). The sanitation of floors was tested with sock samples (n = 41). A total of 328 samples were analyzed for adenosine triphosphate (ATP) and protein residues, aerobic total viable count (TVC), total coliform count (TCC), Escherichia coli, methicillin-resistant Staphylococcus aureus (MRSA), extended-spectrum β-lactamase-producing bacteria (ESBL), and Salmonella spp. After evaluation of these results, the farmers were informed about the findings and trained on improvement in hygiene management personally. The sampling was repeated after 1 year to detect possible changes in hygiene management. The highest bacterial loads (TVC, TCC, and E. coli) were observed in feeding equipment, especially the inner teat of milk feeding buckets. Environmental samples, primarily the sidewalls and back walls of tested pens and hutches, exhibited the lowest bacterial counts and ATP and protein residues. All samples were negative for MRSA and Salmonella spp. In 10.5% of all samples, ESBL was detected, and in 6.8%, ESBL E. coli was detected, predominately in sock samples, followed by feeding equipment samples. Training in hygiene management showed only limited effects. In conclusion, there is still great potential to improve the implementation of hygiene measures in individual calf housing. In particular, more attention should be paid to the cleaning of feeding buckets and artificial teats, as this is a simple means of interrupting the possible spread of pathogens among calves.
Mating behavior of the Iranian fiddler crab Austruca iranica Pretzmann, 1971 (Decapoda: Brachyura: Ocypodidae), with an emphasis on the mate choice of burrow-mating females
Authors: Ghaem-Maghami Alireza , Naderloo Reza
Published: December 2020

Fiddler crabs exhibit two modes of mating: burrow and surface mating. In burrow mating, males wave and attract mate-searching females for mating inside their burrows, whereas in surface mating males search for and mate with females on the surface. We studied the reproductive behavior of Austruca iranica (Pretzmann, 1971), an Indo-West Pacific species, specifically female-mate choice with regard to the size of both male individuals and their burrows. We also compared the size of male and female burrows in the population. Austruca iranica performed both surface and burrow mating despite the different size of the burrow of the two sexes, within the semi-lunar tide cycles at the study site. There was strong size-assortative mating in burrow mating. Burrow-mating females generally chose larger males and wider burrows and even though chosen and rejected males were not different in burrow length, females sampled males with longer than average burrows. Surface-mating females also possessed burrows that were longer than those of the females in the population and this may have enabled them to mate on the surface and breed alone. Regardless of its similarities to some species that only perform burrow mating; the ecology of A. iranica has made it possible for this species to mate on the surface as well as in male-defended burrows. The choice of large males by burrow mating females may provide benefits to females from both the large male itself (e.g., protection) and his wider burrow (e.g., better incubation temperature).
Behind the Scenes of an Exhibition: The Commissioning of Designs in the Records of the Festival Office
Authors: Chow-Thomas Ann
Published: December 2020

The seventieth anniversary of the Festival of Britain occurs in May 2021, providing an opportunity to revisit various aspects of the Festival, not least the various archival collections. The Festival Office records at The National Archives U.K. comprises a range of materials with exciting research potential. This article introduces readers to the collection, highlighting the importance of these records as a unique design-research resource, intersecting with art and photography histories. It will examine the nature of the collection and provide research tips on how to negotiate it effectively. The vast administrative paperwork, some of it amassed through commissioning process, can provide other useful insights. One particular issue is gender in the design profession and how women fared within the Festival’s commissioning process. Previous studies have not only omitted the many lesser known contributions of female artists and designers, but also the nuanced reasons why women artists have not secured successful public commissions during the postwar era. By examining archived original designs by artists Prunella Clough and Hilda Chancellor-Pope, the article reflects on two very different women’s contributions to the Festival; and how decision-making in the commissioning process impacted on the overall look of designs as display.
Cervical spine multiple myeloma and isolated radiotherapy
Authors: Belo Diogo , Reis José Hipólito , Teixeira Joaquim Cruz
Published: December 2020

Multiple myeloma is a hematologic malignancy frequently presenting with spinal lytic lesions. The authors report the case of a patient with an extensively destructive osteolytic MM lesion in the cervical spine treated exclusively with radiotherapy. Computed tomography and magnetic resonance imaging scans showed an arrest of further progression of instability and resolution of the lytic lesion, showing signs of new bone formation. Whereas surgery should be considered for cases of spinal instability and potential neurological injury, this case demonstrates that isolated radiotherapy can be used in select cases to treat MM lesions and restore the structural integrity of the spinal elements.
Extensions to models of the galaxy–halo connection
Authors: Hadzhiyska Boryana , Bose Sownak , Eisenstein Daniel , Hernquist Lars
Published: December 2020

We explore two widely used empirical models for the galaxy–halo connection, subhalo abundance matching (SHAM) and the halo occupation distribution (HOD), and compare them with the hydrodynamical simulation IllustrisTNG (TNG) for multiple statistics quantifying the galaxy distribution at $n_{\rm gal}\approx 1.3\times 10^{-3}\, ({\rm Mpc}\,h^{-1})^{-3}$. We observe that in their most straightforward implementations, both models fail to reproduce the two-point clustering measured in TNG. We find that SHAM models that use the relaxation velocity, Vrelax, and the peak velocity, Vpeak, perform best, and match the clustering reasonably well, although neither captures adequately the one-halo clustering. Splitting the total sample into sub-populations, we discover that SHAM overpredicts the clustering of high-mass, blue, star-forming, and late-forming galaxies and underpredicts that of low-mass, red, quiescent, and early-forming galaxies. We also study various baryonic effects, finding that subhaloes in the dark-matter-only simulation have consistently higher values of their SHAM-proxy properties than their full-physics counterparts. We then consider a 2D implementation of the HOD model augmented with a secondary parameter (environment, velocity anisotropy, σ2Rhalf-mass, and total potential) tuned so as to match the two-point clustering of the IllustrisTNG galaxies on large scales. We analyse these galaxy populations adopting alternative statistical tools such as galaxy–galaxy lensing, void–galaxy cross-correlations, and cumulants of the density field, finding that the hydrodynamical galaxy distribution disfavours σ2Rhalf-mass and the total potential as secondary parameters, while the environment and velocity anisotropy samples are consistent with full physics across all statistical probes examined. Our results demonstrate the power of examining multiple statistics for determining the secondary parameters that are vital for understanding the galaxy–halo connection.
Operando surface science methodology reveals surface effect in charge storage electrodes
Authors: Wang Chao , Ning Yanxiao , Huang Haibo , Li Shiwen , Xiao Chuanhai , Chen Qi , Peng Li , Guo Shuainan , Li Yifan , Liu Conghui , Wu Zhong-Shuai , Li Xianfeng , Chen Liwei , Gao Chao , Wu Chuan , Fu Qiang
Published: December 2020

Surface and interface play critical roles in energy storage devices, calling for operando characterization techniques to probe the electrified surfaces/interfaces. In this work, surface science methodology, including electron spectroscopy and scanning probe microscopy, has been successfully applied to visualize electrochemical processes at operating electrode surfaces in an Al/graphite model battery. Intercalation of anions together with cations is directly observed in the surface region of a graphite electrode with tens of nanometers thickness, the concentration of which is one order higher than that in bulk. An intercalation pseudocapacitance mechanism and a double specific capacity in the electrode surface region are expected based on the super-dense intercalants and anion/cation co-intercalation, which are in sharp contrast to the battery-like mechanism in the electrode bulk. The distinct electrochemical mechanism at the electrode surface is verified by performance tests of real battery devices, showing that a surface-dominant, nanometer-thick graphite cathode outperforms a bulk-dominant, micrometer-thick graphite cathode. Our findings highlight the important surface effect of working electrodes in charge storage systems.
A 2-Year Longitudinal Study of Physical Activity and Cardiovascular Risk in Survivors of Stroke
Authors: Fini Natalie A , Bernhardt Julie , Churilov Leonid , Clark Rebecca , Holland Anne E
Published: December 2020

Objective

The purpose of this study was to explore associations between physical activity, cardiovascular risk factors, mobility, mood, fatigue, and cognition over 2 years following stroke rehabilitation discharge.

Methods

In this longitudinal observational study, survivors of first-ever stroke were evaluated at rehabilitation discharge and 6, 12, and 24 months later. Moderate to vigorous physical activity (MVPA) duration (minutes/day) assessed with an electronic monitor was the primary outcome. Further outcomes included step count, the number and duration of MVPA and sedentary bouts, cardiovascular risk factors (eg, blood pressure, fasting lipid profile, body mass index [BMI]), gait speed and endurance, mood, fatigue, and cognition. Associations between physical activity and cardiovascular risk factors over time were assessed with random-effects regression modeling. Associations between baseline characteristics and physical activity at 2 years were explored using regression modeling.

Results

Seventy-nine participants (68.4% men) with a mean age of 65 years (SD = 14) and a median gait speed of 1.2 m/s (interquartile range = 0.8 to 1.4) were included at baseline. Associations were found between higher physical activity (MVPA duration, number and duration of MVPA bouts) and lower BMI. Better gait speed, endurance, and cognition at baseline were associated with higher MVPA and step count at 2 years.

Conclusions

Duration and bouts of MVPA are associated with BMI. Increasing MVPA and bouts of MVPA may be a valuable treatment goal to reduce cardiovascular risk in survivors of stroke.

Impact

This 2-year study found that MVPA is associated with important cardiovascular risk factors in people who have survived stroke. Understanding these associations could be useful for developing effective treatments to prevent recurrent stroke.

Lay Summary

Performing MVPA and accumulating in bouts of at least 10 minutes might be challenging, but it could be an important component of treatments to reduce cardiovascular risk after stroke.
Markets, Social Networks, and Internally Displaced Persons: Gaining and Maintaining Market Access in the Democratic Republic of Congo
Authors: Binda Gloria Nguya , Koch Dirk Jan
Published: December 2020

Arriving in a new environment, internally displaced persons (IDPs) have to rebuild their lives and find a way to make a living. In this situation, IDP women in the Democratic Republic of Congo (DRC) sustain their families by engaging in a range of economic activities, but particularly petty trade in markets. In this regard, eastern DRC offers an opportunity to better understand how IDP women engage in and navigate urban markets. Based on field research conducted in Bukavu city in South Kivu, where there are no IDP camps, this article looks at how IDP women gain access to markets and the role that social relationship and networks play in this process. Although IDPs women are often conceptualised as vulnerable and exploited, this research demonstrates that they proactively make use of opportunities in an effective way to create new livelihood opportunities. Existing studies also indicate that newcomers to an urban location can initially only access informal markets, and if they are successful there, then they might access formal markets afterwards. However, the present research shows that IDP women were more successful in integrating in formal markets than in informal markets.
Targeting the Intestine to Treat Osteoporosis
Authors: McCabe Laura , Schepper Jonathan , Rios Naiomy , Kang HoJun , Parameswaran Narayanan
Published: December 2020

Osteoporosis is estimated to affect 200 million women worldwide. After the age of 50, 1 in 3 women and 1 in 5 men will experience an osteoporotic fracture and its associated pain, increased dependency, morbidity and mortality (National Osteoporosis Foundation). While there are a variety of pharmaceuticals available to treat osteoporosis, the number of people with osteoporosis continues to grow. This is in part due to reduced treatment compliance and reduced prescriptions for osteoporosis medications (Khosla and Shane, 2016). Thus, there is a need for expansion of safe, non‐prescription based treatment options for prevention or treatment of early stage osteoporosis. My talk will discuss development of therapeutics targeting the gut‐bone axis, which represents a novel, rapidly growing area of research. Reports from our lab and others indicate a key role for the microbiota in regulating bone density. Prebiotic and probiotic modulation of the intestinal microbiota and gut function is demonstrated to benefit bone health parameters in animal models and humans. Our studies and reports by others indicate that bone responses to gut manipulations are regulated by many factors including sex hormones, inflammation status, disease condition and age. Identification of specific signaling mechanisms (gut barrier function, microbiota composition, probiotic metabolites and secretory factors) will lead to further optimization of straightforward and cost‐effective treatments.

Support or Funding Information

NIH DK101050, NIH AT007695

This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Pro‐inflammatory Cytokine TNFα Induces Endoplasmic Reticulum Stress Through Reactive Oxygen Species Generation in Human Airway Smooth Muscle Cells
Authors: Yap John , Marin Natalia Mathieu , Baqal Omar Javed , Delmotte Philippe , Prakash YS , Sieck Gary C.
Published: December 2020

Airway inflammation plays a key role in asthma. In various diseases, inflammation leads to an increase in reactive oxygen species (ROS) generation and is associated with accumulation of unfolded proteins leading to endoplasmic reticulum (ER) stress. In response to ER stress, a homeostatic signaling cascade is triggered to restore normal function by halting protein translation and activating protein degradation and expression of molecular chaperones involved in protein folding. Three ER stress protein markers located at the ER membrane are involved in this signaling cascade: protein kinase RNA‐like endoplasmic reticulum kinase (PERK), activating transcription factor 6 (ATF6) and inositol‐requiring enzyme 1 (IRE1α). In particular, phosphorylation of IRE1α catalyzes the alternative splicing of XBP1 mRNA leading to expression of the active XBP1 transcription factor. In this study, we hypothesize that pro‐inflammatory cytokine TNFα induces ROS production triggering ER stress in human airway smooth muscle (hASM). hASM cells were isolated from lung specimen incidental to patient surgery and exposed to TNFα (20 ng/ml) for 1, 3, 6, 12 or 24 h. To measure ROS production, hASM cells were loaded with the general oxidative stress indicator CM‐H2DCFDA or with the mitochondrial superoxide indicator MitoSOX™ Red. The CM‐H2DCFDA and MitoSOX™ Red signals were visualized using a Nikon A1R confocal imaging system. Images were analyzed using ImageJ. Exposure of hASM to tunicamycin (2 μg/ml) was used as a positive control for ER stress. Expression of IRE1α and PERK were determined by Western blot. Phosphorylation of IRE1α was also evaluated by immunoprecipitation and Western blot (Wes Simple Western™ system). The expression of the spliced isoform of the transcription factor XBP1 was examined by quantitative real‐time PCR (RT‐PCR). We found that ROS production increased in hASM within 1 h of TNFα exposure, followed by an increase in IRE1α phosphorylation within 1–3 h. Finally after 3–6 h, there was an increase in alternative splicing of XBP1 mRNA. Together these results show that the pro‐inflammatory cytokine TNFα increases ROS generation in hASM cells and induces an ER stress response that includes an increase in IRE1α phosphorylation and splicing of XBP1. This ER stress response may affect many downstream targets, among which we believe Mfn2 is a major target which affects mitochondrial Ca2+ buffering, with specific effects on hASM force and/or increased cell proliferation associated with asthma.

Support or Funding Information

NIH grant HL126451

This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Antibacterial activity of methanolic extracts from Dunaliella salina and Chlorella vulgaris
Authors: Medina‐Jaritz Nora B. , Carmona‐Ugalde Luis Fernando , Lopez‐Cedillo Julio Cesar , Leon F. Sandra L. Ruiloba‐De
Published: December 2020

Many antibiotic substances have been isolated from algae, but little from marine green microalgae like Dunaliella salina. To examine the antibiotic effect of extracts from Dunaliella salina and Chlorella vulgaris, methanolic extracts were tested against Proteus vulgaris, Bacillus subtilis, Escherichia coli, Staphylococcus aureus, Salmonella typhi ATCC 6534, E. coli ATCC 8739, S. aureus ATCC 25923 and B. subtilis ATCC 6635.

Algae biomass were subjected to methanol/acetic acid treatments, dried and resuspended in methanol. The microorganisms were grown in a Mueller Hinton culture media; for the agar diffusion test were adjusted to tube 1 nephelometer and spread on plates; extracts were impregnated onto paper discs. After incubation inhibition zones around each disc were measured. One‐way ANOVA Dunnett analysis was performed.

The D. salina extract showed significant antibacterial activity against all microorganisms, especially to Proteus vulgaris and Salmonella typhi ATCC 6534; while the C. vulgaris extract did not show significant antibacterial activity against all microorganisms, but the bigger inhibition halos result with B. subtilis and B. subtilis ATCC 6635.

Support from SIP‐IPN and COFAA‐IPN.
Development of student metacognition and progression of expertise across chemistry and biochemistry classes (LB114)
Authors: Rosenberg Martina , Knottenbelt Sushilla , Whalen Lisa
Published: December 2020

Despite repeated exposure while progressing along a typical Undergraduate Science curriculum, learners find many fundamental concepts challenging to master. A recent report by the National Academy of Sciences identifies as one of the enduring challenges in education the application of material in a new context. However, when the mind’s ability to monitor and control its own activities is facilitated (metacognitive skills), the ability to transfer improves.

This investigation aims to determine which previously acquired concepts from other classes are difficult to apply in an undergrad introductory level Biochemistry course and simultaneously explores the students’ metacognitive awareness. Biochemistry is often taken as the final science course and is taught in an active learning environment, including group work and frequent prompts for reflection.

A pre‐instruction test revealed a moderate degree of mastery of problems that were identical to questions used in the finals of prerequisite chemistry classes. Within the biochemistry class pre‐ vs. post‐test performance of students shows varying degrees of acquisition and retention for specific. The acuity of the answers for individual questions did not correlate to confidence levels reported by the students while taking the tests. At the same time, a survey of learning habits indicates that biochemistry students are less anxious about exams than students in introductory chemistry classes. They are also more likely to regularly attend out‐of‐class help sessions and to meet their peers outside of class to study. Although they are equally unlikely to complete practice problems in addition to their homework, biochemistry students were ‘often’ able to identify what they did not know, but only ‘occasionally’ able to get help with what they did not know. At the end of the semester the more successful students reported their use of more study methods aside from adjustment of their study strategies indicating deliberate use of self‐regulatory mechanisms.

The exploratory data presented warrant further investigation of the connection between content mastery and metacognitive awareness and will contribute to a framework exploring transfer of content and skills across a typical undergraduate science track. The authors have applied for NSF funding to continue this work.
Impact of the European Board of Pediatric Surgery examination on career progression: a cross-sectional survey study
Authors: Kawano Takafumi , Cascio Salvatore , MacKenzie Rosemary , Muensterer Oliver J.
Published: December 2020

Background:

The 2-part examination of the European Board in Pediatric Surgery (EBPS) was established in 2005 with the aim of ensuring harmonization of standards of training in Europe. The aim of this study was to assess the impact of the examination on career progression using a validated questionnaire.

Methods:

Between 2005 and 2016 a total of 227 candidates successfully passed part 2 of the EBPS examination. Of these, we were able to successfully contact 160 candidates by email and ask them to complete a validated online questionnaire, the Career Success Scale (CSS). Eighty-five candidates answered and 49 completed all items of the questionnaire (recall of 31%). Information on demographics, work environment, publication output, and self-reflecting personal opinion on the impact of EBPS certification on career progression was also queried.

Results:

A recall of 31% was obtained (49/160). Most respondents were male (82%), had published scientific manuscripts in peer-reviewed journals (93%), were actively presenting at conferences (96%), and believed that passing the examination helped them reach their career goals (61%). Involvement in multicenter studies was reported by 51% of respondents, 16% had obtained research awards, 16% received scholarships, and 9% reported research as their principal activity.

Conclusion:

Candidates who passed the European Board Exam reported a high level of academic activity. Most of them believed that passing the exam had a positive effect on their career development.
Machine learning analysis highlights the down-trending of the proportion of COVID-19 patients with a distinct laboratory result profile
Authors: Yang He S. , Hou Yu , Zhang Hao , Chadburn Amy , Westblade Lars F. , Fedeli Richard , Steel Peter A.D. , Racine-Brzostek Sabrina E. , Velu Priya , Sepulveda Jorge L. , Satlin Michael J. , Cushing Melissa M. , Kaushal Rainu , Zhao Zhen , Wang Fei
Published: December 2020

Background

New York City (NYC) experienced an initial surge and gradual decline in the number of SARS-CoV-2 confirmed cases in 2020. A change in the pattern of laboratory test results in COVID-19 patients over this time has not been reported or correlated with patient outcome.

Methods

We performed a retrospective study of routine laboratory and SARS-CoV-2 RT-PCR test results from 5,785 patients evaluated in a NYC hospital emergency department from March to June employing machine learning analysis.

Results

A COVID-19 high-risk laboratory test result profile (COVID19-HRP), consisting of 21 routine blood tests, was identified to characterize the SARS-CoV-2 patients. Approximately half of the SARS-CoV-2 positive patients had the distinct COVID19-HRP that separated them from SARS-CoV-2 negative patients. SARS-CoV-2 patients with the COVID19-HRP had higher SARS-CoV-2 viral loads, determined by cycle-threshold values from the RT-PCR, and poorer clinical outcome compared to other positive patients without COVID19-HRP. Furthermore, the percentage of SARS-CoV-2 patients with the COVID19-HRP has significantly decreased from March/April to May/June. Notably, viral load in the SARS-CoV-2 patients declined and their laboratory profile became less distinguishable from SARS-CoV-2 negative patients in the later phase.

Conclusions

Our study visualized the down-trending of the proportion of SARS-CoV-2 patients with the distinct COVID19-HRP. This analysis could become an important tool in COVID-19 population disease severity tracking and prediction. In addition, this analysis may play an important role in prioritizing high-risk patients, assisting in patient triaging and optimizing the usage of resources.
Rotavirus disease and health care utilisation among children under 5 years of age in highly developed countries: a systematic review and meta-analysis
Authors: Ardura-Garcia Cristina , Kreis Christian , Rakic Milenko , Jaboyedoff Manon , Mallet Maria Christina , Low Nicola , Kuehni Claudia E.
Published: December 2020

Background

Rotavirus (RV) infection is the leading cause of diarrhoea-associated morbidity and mortality globally among children under 5 years of age. RV vaccination is available, but has not been implemented in many national immunisation plans, especially in highly developed countries. This systematic review aimed to estimate the prevalence and incidence of health care use for RV gastroenteritis (RVGE) among children aged under 5 years in highly developed countries without routine RV vaccination.

Methods

We searched MEDLINE and Embase databases from January 1st 2000 to December 17th 2018 for publications reporting on incidence or prevalence of RVGE-related health care use in children below 5 years of age: primary care and emergency department (ED) visits, hospitalisations, nosocomial infections and deaths. We included only studies with laboratory-confirmed RV infection, undertaken in highly developed countries with no RV routine vaccination plans. We used random effects meta-analysis to generate summary estimates with 95% confidence intervals (CI) and prediction intervals.

Results

We screened 4033 abstracts and included 74 studies from 21 countries. Average incidence rates of RVGE per 100 000 person-years were: 2484 (95% CI 697-5366) primary care visits, 1890 (1597-2207) ED visits, 500 (422-584) hospitalisations, 34 (20-51) nosocomial infections and 0.04 (0.02-0.07) deaths. Average proportions of cases of acute gastroenteritis caused by RV were: 21% (95% CI 16-26%) for primary care visits; 32% (25-38%) for ED visits; 41% (36-47%) for hospitalisations, 29% (25-34%) for nosocomial infections and 12% (8-18%) for deaths. Results varied widely between and within countries, and heterogeneity was high (I2>90%) in most models.

Conclusion

RV in children under 5 years causes many healthcare visits and hospitalisations, with low mortality, in highly developed countries without routine RV vaccination. The health care use estimates for RVGE obtained by this study can be used to model RV vaccine cost-effectiveness in highly developed countries.

Take home message

RV-caused illness leads to a high burden of health care usage in highly developed countries who have not introduced RV vaccination.
A BTB-Domain Transcription factor Recruits Chromatin Remodelers and a Histone Chaperone during the exit from Pluripotency
Authors: Olivieri Daniel , Paramanathan Sujani , Bardet Anaïs F. , Hess Daniel , Smallwood Sébastien A. , Elling Ulrich , Betschinger Joerg
Published: December 2020

Transcription factors (TFs) harboring a btb (Broad-Complex, Tramtrack and Bric a brac) domain play important roles in development and disease. They are thought to recruit transcriptional modulators to DNA through their btb domain. However, a systematic molecular understanding of this TF family is lacking. Here, we identify the zinc finger btb-TFZbtb2in a genetic screen for regulators of exit from pluripotency and dissect its mechanistic mode of action. We show that ZBTB2 binds the chromatin remodeler Ep400 to mediate downstream transcription. Independently, the btb domain directly interacts with the chromatin remodeller NuRD and the histone chaperone HiRA via the GATAD2A/B and UBN2 subunits, respectively. NuRD recruitment is a common feature of btb-TFs and we propose by phylogenetic analysis that this is an evolutionary ancient property. Binding to UBN2, in contrast, is specific to ZBTB2 and requires a C-terminal extension of the btb domain. This study therefore identifies a btb-domain TF that recruits chromatin modifiers and a histone chaperone during a developmental cell state transition, and defines unique and shared molecular functions of the btb-domain TF family.
Gut microbiome couples gut and brain during calorie restriction in treating obesity
Authors: Zeng Qiang , Wang Qi , Xiang Tianyuan , Ou Lei , Wu Xiaoling , Cai Kaiye , Geng Chunyu , Han Mo , Li Zhongxia , Li Zhonglin , Wang Wen , Yang Tingting , Li Fengyun , Ma Huimin , Zhao Xiaojuan , Mi Na , Gao Hui , Tong Li , Zhang Chi , Wang Linyuan , Yan Bin , Yu Ziya , Wang Ziyu , Lan Canhui , Wang Xiaoning , Li Yongli , Wang Jun
Published: December 2020

Calorie restriction (CR) has been widely recognized for its effect in reducing body weight and alleviating diabetes in humans, as well as prolonging life span in animal studies. Gut microbiome shifts contribute to part of the effects of CR, but little is known regarding their influences except on metabolism and immunity. Here we monitored gut microbiome using metagenomics and metatranscriptomics in obese individuals undergoing CR, and revealed microbial determinants that could contribute to successful weight loss. Microbiome changes are linked to changes in blood metabolome and hormones, which eventually correlate to brain functional changes as studied using functional magnetic resonance imaging (fMRI). Brain functional shifts indicate response of central neural system (CNS) to CR, and microbiome constitutes the keystone of gut-brain axis. Animal experiment further reaffirms the gut microbiome changes, metabolic and hormonal shifts of CR, while proteomic analysis of brain tissues suggest that epigenetic modifications of key proteins could explain responses of CNS to CR. Our study establishes linkage between CR, gut microbiome, metabolome/ hormones and CNS function, and demonstrates that CR has multi-facet, coordinated effects on the host, of which many could contribute to weight loss and other beneficial effects.
Ribavirin shows antiviral activity against SARS-CoV-2 and downregulates the activity of TMPRSS2 and the expression of ACE2 In Vitro
Authors: Unal Mehmet Altay , Bitirim Ceylan Verda , Summak Gokce Yagmur , Bereketoglu Sidar , Zeytin Inci Cevher , Bul Omur , Gurcan Cansu , Aydos Dunya , Goksoy Ezgi , Kocakaya Ebru , Eran Zeynep , Murat Merve , Demir Nil , Somers Julia , Demir Emek , Nazir Hasan , Ozkan Sibel Aysil , Ozkul Aykut , Azap Alpay , Yilmazer Acelya , Akcali Kamil Can
Published: December 2020

Ribavirin is a guanosine analog and has a broad-spectrum antiviral activity against RNA viruses. Based on this, we aimed to show the anti-SARS-CoV-2 activity of this drug molecule via in vitro, in silico and molecular techniques. Ribavirin showed antiviral activity in Vero E6 cells following SARS-CoV-2 infection. In silico analysis suggested that Ribarivin has a broad-spectrum impact on Vero E6 cells. According to the detailed molecular techniques, Ribavirin was shown to decrease TMPRSS2 expression both at mRNA and protein level 48 hours after treatment. The suppressive effect of Ribavirin in ACE2 protein expression was shown to be dependent on cell types. Finally, proteolytic activity assays showed that Ribavirin also showed an inhibitory effect on TMPRSS2 enzyme. As a conclusion, Ribavirin is a potential antiviral drug for the treatment against SARS-CoV-2, and it interferes with the effect of TMPRSS2 and ACE2 expression.
Monocarboxylate transporter antagonism reveals metabolic vulnerabilities of viral-driven lymphomas
Authors: Bonglack Emmanuela N. , Messinger Joshua E. , Cable Jana M. , Parnell K. Mark , Ch’ng James , Christofk Heather R. , Luftig Micah A.
Published: December 2020

Epstein-Barr Virus (EBV) is a ubiquitous herpesvirus that typically causes asymptomatic infection but can promote B lymphoid tumors in the immune-suppressed.In vitro, EBV infection of primary B cells stimulates glycolysis during immortalization into lymphoblastoid cell lines (LCLs). Lactate export during glycolysis is crucial for continued proliferation of many cancer cells-part of a phenomenon known as the “Warburg effect,” and is mediated by the monocarboxylate transporters 1 and 4 (MCT1 and MCT4). However, the role of MCT1/4 has yet to be studied in EBV-associated malignancies which display Warburg-like metabolismin vitro. Here, we show that EBV infection of B lymphocytes directly promotes temporal induction of MCT1 and MCT4 through the viral proteins EBNA2 and LMP1 respectively, with MCT1 being induced early after infection and MCT4 late. Remarkably, singular MCT1 inhibition early, and dual MCT1/4 inhibition in LCLs using a novel MCT4-selective inhibitor led to growth arrest and lactate buildup. Metabolic profiling in LCLs revealed significatly reduced oxygen consumption rates (OCR) and NAD+/NADH ratios, contrary to prevous observations of increased OCR and unaltered NAD+/NADH ratios in MCT1/MCT4-inhibited cancer cells. Furthermore, U-13C6 glucose labeling of MCT1/4-inhibited LCLs also revealed increased labeling of glutathione in the presence of elevated ROS and depleted glutathione pools, as well as increased labeling ofde novopyrimidine biosynthetic intermediates, suggesting broad effects on LCL metabolism. These vulnerabilities sensitized LCLs as well as EBV+, and the related gammaherpesvirus KSHV+ lymphoma cell lines to killing by metformin and phenformin, pointing at a novel therapeutic approach for viral lymphomas.