bluuebunny/crossref_metadata_2025 huggingface dataset:
Upadacitinib Treatment Improves Symptoms of Bowel Urgency and Abdominal Pain, and Correlates With Quality of Life Improvements in Patients With Moderate to Severe Ulcerative Colitis
Authors: Ghosh Subrata , Sanchez Gonzalez Yuri , Zhou Wen , Clark Ryan , Xie Wangang , Louis Edouard , Loftus Edward V , Panes Julian , Danese Silvio
Published: June 2021

Background and Aims

Bowel urgency and abdominal pain are impactful, yet under-appreciated ulcerative colitis symptoms and not commonly assessed in clinical trials. We evaluated how these symptoms may improve with upadacitinib treatment and correlate with clinical and health-related quality of life [HRQOL] outcomes in the phase 2b U-ACHIEVE study.

Methods

Patients aged 18–75 years, with moderately to severely active ulcerative colitis, were randomised to receive placebo or upadacitinib (7.5, 15, 30, or 45 mg once daily [QD]). Bowel urgency and abdominal pain were evaluated at baseline and Weeks 2, 4, 6, and 8. Week 8 correlations were evaluated between bowel urgency/abdominal pain with clinical [Mayo subscores and high-sensitivity C-reactive protein and faecal calprotectin measurements] and HRQOL outcomes [Inflammatory Bowel Disease Questionnaire and 36-Item Short Form Health Survey scores].

Results

A greater proportion of patients [n = 250] reported no bowel urgency and less abdominal pain with upadacitinib treatment compared with placebo, with improvements observed as early as 2 weeks. At Week 8, patients receiving the 45-mg QD dose had the greatest improvements versus placebo, with 46% reporting no bowel urgency [vs 9%; p ≤ 0.001] and 38% reporting no abdominal pain [vs 13%; p = 0.015]. At Week 8, moderate correlations were found between bowel urgency or abdominal pain and most clinical and HRQOL outcomes.

Conclusions

Induction treatment with upadacitinib demonstrated significant reductions in bowel urgency and abdominal pain compared with placebo. These symptoms also correlate to clinical and HRQOL outcomes, supporting their use to monitor disease severity and other treatment outcomes.
Artificial intelligence to generate medical images: augmenting the cardiologist’s visual clinical workflow
Authors: Olender Max L , de la Torre Hernández José M , Athanasiou Lambros S , Nezami Farhad R , Edelman Elazer R
Published: June 2021

Artificial intelligence (AI) offers great promise in cardiology, and medicine broadly, for its ability to tirelessly integrate vast amounts of data. Applications in medical imaging are particularly attractive, as images are a powerful means to convey rich information and are extensively utilized in cardiology practice. Departing from other AI approaches in cardiology focused on task automation and pattern recognition, we describe a digital health platform to synthesize enhanced, yet familiar, clinical images to augment the cardiologist’s visual clinical workflow. In this article, we present the framework, technical fundamentals, and functional applications of the methodology, especially as it pertains to intravascular imaging. A conditional generative adversarial network was trained with annotated images of atherosclerotic diseased arteries to generate synthetic optical coherence tomography and intravascular ultrasound images on the basis of specified plaque morphology. Systems leveraging this unique and flexible construct, whereby a pair of neural networks is competitively trained in tandem, can rapidly generate useful images. These synthetic images replicate the style, and in several ways exceed the content and function, of normally acquired images. By using this technique and employing AI in such applications, one can ameliorate challenges in image quality, interpretability, coherence, completeness, and granularity, thereby enhancing medical education and clinical decision-making.
Contrasting Internet Adoption in Early and Advanced Old Age: Does Internet Self-Efficacy Matter?
Authors: Jokisch Mario R , Scheling Louisa , Doh Michael , Wahl Hans-Werner
Published: June 2021

Objectives

Understanding why older adults (including those in very old age) use or do not use the Internet can build on the technology acceptance model (TAM). In this cross-sectional study, we translate the TAM to the Internet and assume that perceived usefulness of the Internet (PUI) and perceived ease of use of the Internet (PEUI) will be revealed as major predictors of behavioral intention to use the Internet (BII). Additionally, we consider the role of Internet self-efficacy (ISE) as another major factor for older adults’ Internet use. We also argue that life phase, particularly early as opposed to advanced old age, may moderate how PUI, PEUI, and ISE relate to BII.

Methods

A sample of 1,200 older adults aged 60 years and older (60–74 years, n = 658; 75–99 years, n = 542) was randomly drawn from the city of Stuttgart, Germany. Sociodemographic variables and major indicators of TAM and ISE were assessed based on a computer-assisted telephone interviewing procedure.

Results

Latent structural equation modeling revealed that PUI is the more important predictor of BII in older adults. Furthermore, ISE revealed statistically meaningful positive links with PUI, PEUI, and BII. Multigroup comparison revealed that PUI had a stronger linkage with BII in early old age, whereas ISE was more important for BII in advanced old age.

Discussion

The results suggest that ISE may enrich the network of TAM constructs among older adults in general but specifically in advanced old age.
The effect of n-3 polyunsaturated fatty acids-enriched hen eggs consumption on IgG and total plasma protein N-glycosylation in healthy individuals and cardiovascular patients
Authors: Stupin Ana , Cvetko Ana , Kralik Gordana , Mihalj Martina , Šušnjara Petar , Kolobarić Nikolina , Breškić Ćurić Željka , Lukinac Ana Marija , Kibel Aleksandar , Selthofer-Relatić Kristina , Jukić Ivana , Stupin Marko , Kolar Luka , Kralik Zlata , Grčević Manuela , Galović Olivera , Mihaljević Zrinka , Matić Anita , Juranić Brankica , Gornik Olga , Lauc Gordan , Drenjančević Ines
Published: June 2021

This study determined the effect of n-3 polyunsaturated fatty acids (n-3 PUFAs)-enriched hen eggs consumption on immunoglobulin G (IgG) and total plasma protein N-glycan profiles and inflammatory biomarkers level in healthy individuals (N = 33) and cardiovascular (CV) patients (N = 21). Subjects were divided to Control-Healthy and Control-CV subgroups [consumed three regular hens’ eggs/daily (249 mg n-3 PUFAs/day)], and n-3 PUFAs-Healthy and n-3 PUFAs-CV subgroups [consumed three n-3 PUFAs-enriched hen eggs/daily (1053 mg n-3 PUFAs/day)] for 3 weeks. Serum-free fatty acids profile and high-sensitivity C-reactive protein, interleukin 6 and 10 (IL-6, IL-10) and tumor necrosis factor alpha were measured. Total plasma protein and IgG N-glycome have been profiled before and after dietary protocols. Serum n-3 PUFAs concentration significantly increased following n-3 PUFAs hen eggs consumption in both n-3 PUFAs-Healthy and n-3 PUFAs-CV. IL-10 significantly increased in both Healthy subgroups, whereas no change occurred in CV subgroups. Derived IgG N-glycan traits: bisecting N-acetylglucosamine (B) significantly decreased in n-3 PUFAs-Healthy, whereas agalactosylation (G0) and core fucosylation (CF) significantly increased in Control-Healthy. Derived total plasma protein N-glycan traits: high branching glycans, trigalactosylation, tetragalactosylation, trisialylation, tetrasialylation and antennary fucosylation significantly decreased, whereas G0, monogalactosylation (G1), neutral glycans (S0), B, CF and oligomannose structures significantly increased in n-3 PUFAs-CV. Digalactosylation significantly decreased, and G0, G1, S0, disialylation, B and CF significantly increased in Control-CV. n-3 PUFAs consumption alters IgG N-glycan traits and IL-10 in healthy individuals, and total plasma protein N-glycan traits in CV patients, by shifting them toward less inflammatory N-glycosylation profile.
Dosage-Dependent Impact of Acute Serotonin Enhancement on Transcranial Direct Current Stimulation Effects
Authors: Melo Lorena , Mosayebi-Samani Mohsen , Ghanavati Elham , Nitsche Michael A , Kuo Min-Fang
Published: June 2021

Background

The serotonergic system has an important impact on basic physiological and higher brain functions. Acute and chronic enhancement of serotonin levels via selective serotonin reuptake inhibitor administration impacts neuroplasticity in humans, as shown by its effects on cortical excitability alterations induced by non-invasive brain stimulation, including transcranial direct current stimulation (tDCS). Nevertheless, the interaction between serotonin activation and neuroplasticity is not fully understood, particularly considering dose-dependent effects. Our goal was to explore dosage-dependent effects of acute serotonin enhancement on stimulation-induced plasticity in healthy individuals.

Methods

Twelve healthy adults participated in 7 sessions conducted in a crossover, partially double-blinded, randomized, and sham-controlled study design. Anodal and cathodal tDCS was applied to the motor cortex under selective serotonin reuptake inhibitor (20 mg/40 mg citalopram) or placebo medication. Motor cortex excitability was monitored by single-pulse transcranial magnetic stimulation.

Results

Under placebo medication, anodal tDCS enhanced, and cathodal tDCS reduced, excitability for approximately 60–120 minutes after the intervention. Citalopram enhanced and prolonged the facilitation induced by anodal tDCS regardless of the dosage while turning cathodal tDCS-induced excitability diminution into facilitation. For the latter, prolonged effects were observed when 40 mg was administrated.

Conclusions

Acute serotonin enhancement modulates tDCS after-effects and has largely similar modulatory effects on motor cortex neuroplasticity regardless of the specific dosage. A minor dosage-dependent effect was observed only for cathodal tDCS. The present findings support the concept of boosting the neuroplastic effects of anodal tDCS by serotonergic enhancement, a potential clinical approach for the treatment of neurological and psychiatric disorders.
Optimizing the spring constants of forced, damped and circular spring-mass systems—characterization of the discrete and periodic bi-Laplacian operator
Authors: de Oliveira L L A , Travaglia M V
Published: June 2021

We optimize the spring constants $k^{i,j}$ (stiffness) of circular spring-mass systems with nearest-neighbour (NN) and next-nearest-neighbour (NNN) springs only. In this optimization problem, such systems are also subjected to damping and periodic external forces. The function to be minimized is the average ratio of the square norm of the on-site internal forces (response) to the square norm of the external on-site forces (input). Under the average of this response/input ratio is meant the average over time and over all configurations of external forces. As main result, it is established that the optimum stiffness matrix converges to the discrete and periodic bi-Laplacian operator as the size $n$ of the system increases. Such a result is obtained under the following assumptions: (a) the system has the natural mode shape (eigenvector) of alternating $1$s and $-1$s; and (b) the (external) forcing frequency is at least $1.095$ times higher than the highest natural frequency. It is remarkable that this optimum stiffness matrix exhibits negative stiffness for the springs linking NNN point masses. More specifically, as $n$ increases, $0> k^{i,i+2} \, \, = \, \, - \tfrac{1}{4} \, k^{i,i+1}$ is the relation between the optimum NNN spring constant and the optimum NN spring constant. Such systems illustrate that the introduction of negative stiffness springs in some specific positions does in fact reduce the average response/input ratio. Numerical tables illustrating the main result are given.
Effects of graded levels of xylo-oligosaccharides on growth performance, serum parameters, intestinal morphology, and intestinal barrier function in weaned piglets
Authors: Chen Yuxia , Xie Yining , Zhong Ruqing , Han Hui , Liu Lei , Chen Liang , Zhang Hongfu , Beckers Yves , Everaert Nadia
Published: June 2021

The objective of this study was to investigate the effects of xylo-oligosaccharides (XOSs) supplementation on growth performance, serum parameters, small intestinal morphology, intestinal mucosal integrity, and immune function in weaned piglets. A total of 240 weaned piglets with an average body weight (BW) of 8.82 ± 0.05 kg (28 d of age) were assigned randomly to four dietary treatments in a 28-d trial, including a control (CON) diet and three diets with XOS supplementation at the concentration of 100 (XOS100), 500 (XOS500), and 1,000 (XOS1000) mg/kg. There were four replicates per treatment with 15 pigs per pen. From day 1 to 14, there were no differences (P > 0.05) in average daily gain (ADG), average daily feed intake, and gain to feed ratio (G:F) during the different treatments. The different doses of XOSs showed a quadratic effect on BW on day 28, ADG, and G:F on day 1 to 28 of piglets (P < 0.05). From day 15 to 28, ADG of pigs fed the XOS500 diet was higher (P < 0.05) than pigs fed the CON diet. During the overall period (day 1 to 28), pigs fed the XOS500 diet had a higher BW, ADG, and G:F than pigs fed the CON diet (P < 0.05). In addition, compared with the CON group, the XOS500 group had significantly higher serum total antioxidant capacity, total superoxide dismutase and catalase levels, and lower malondialdehyde levels on days 14 and 28 (P < 0.05). The serum immunoglobulin G (IgG) concentration in the XOS500 group was also significantly higher compared with the CON group on days 14 and 28 (P < 0.05). However, serum immunoglobulin A and immunoglobulin M were not affected by the dietary treatments. Supplementation of XOS500 to the feed significantly increased the villus height (VH) and VH to crypt depth ratio in the jejunum and ileum in comparison with the CON and XOS1000 groups. Moreover, the XOS500 group significantly elevated the expression levels of occludin and zonula occludens protein-1 in the ileum compared with the CON group. The ileal interleukin (IL)-1β, IL-8, and interferon (IFN)-γ mRNA expression levels in the XOS100 and XOS500 groups were markedly lower than in the CON group. In contrast, the ileal IL-10 mRNA expression levels were remarkably higher in the XOS500 than in the CON group. In conclusion, XOSs have a beneficial effect on growth performance by improving serum antioxidant defense system, serum IgG, small intestinal structure, and intestinal barrier function in weaned piglets.
Public Service Motivation as a Predictor of Corruption, Dishonesty, and Altruism
Authors: Gans-Morse Jordan , Kalgin Alexander , Klimenko Andrey , Vorobyev Dmitriy , Yakovlev Andrei
Published: June 2021

Understanding how Public Service Motivation (PSM) is tied to ethical or unethical conduct is critically important, given that civil servants and other public-sector employees throughout the world have been shown to exhibit high PSM levels. However, empirical evidence about the relationship between PSM and ethical or unethical behavior remains limited, due in part to the challenges of observing unethical conduct and overcoming social desirability bias in self-reported measures. We address these challenges by employing incentivized experimental games to study the relationships between PSM and two types of unethical behavior—corruption and dishonesty—as well as one type of ethical behavior: altruism. Based on data from approximately 1,870 university students at three research sites in Russia and Ukraine, we find evidence of a robust negative association between PSM and willingness to engage in corruption and a positive association between PSM and altruistic behavior. Results concerning dishonesty are more mixed. Our findings indicate that corruption and dishonesty are related yet fundamentally distinct concepts, particularly with respect to their compatibility with PSM. The findings additionally demonstrate that hypotheses about PSM and behavioral ethics generated in the Western context generalize well to the starkly different institutional context of the former Soviet Union.
Activation of 5-HT 1b/d receptor restores the cognitive function by reducing glutamate release, deposition of β-amyloid and TLR-4 pathway in the brain of scopolamine-induced dementia in rat
Authors: Tripathi Alok Shiomurti , Bansod Prajakta , Swathi K P
Published: June 2021

Objectives

This study evaluates the effect of 5-HT 1b/d agonist on cognitive function in scopolamine (SPN)-induced dementia in the rat.

Methods

Dementia was induced by administration of SPN 2 mg/kg/day, intraperitoneally, for a duration of 21 days. The effect of zolmitriptan (ZMT) 30 mg/kg, intraperitoneally, was observed on cognitive function, and the parameters of oxidative stress like malondialdehyde (MDA) level, nitric oxide (NO), superoxide dismutase (SOD) and glutathione peroxidase (GPX) were estimated at the end. Histopathology study of brain tissue was performed for the determination of β-amyloid peptide, and qRT-PCR was used to determine the mRNA expression of Toll-like receptor 4 (TLR-4), IL-17 and β-amyloid.

Key findings

Data of the study suggested that treatment with ZMT alone and in combination with DMP (dextromethorphan) significantly (P < 0.01) decreases the escape latency in conditioned avoidance response (CAR) and transfer latency in elevated plus maze (EPM) as compared with negative control group. Moreover, the result of Morris water maze (MWM) shows an increase in retention time and a decrease in escape latency in ZMT alone and in combination with DMP-treated group of SPN-induced dementia than in the negative control group. There was a significant decrease in MDA and NO and increase in SOD and GPX in the brain tissues of ZMT and ZMT + DMP-treated group than negative control group. Histopathology study also suggested that the concentration of Aβ peptide decreases in the brain tissues in ZMT and ZMT + DMP-treated group than the negative control group. Moreover, ZMT treatment ameliorates the altered mRNA expression of TLR-4 and IL-17 in the brain tissue of SPN-induced dementia rat.

Conclusions

In conclusion, ZMT restores the cognitive functions and impaired memory in SPN-induced dementia in the rat by decreasing oxidative stress and Aβ peptide in the brain tissue of rat.
An update on redox signals in plant responses to biotic and abiotic stress crosstalk: insights from cadmium and fungal pathogen interactions
Authors: Romero-Puertas María C , Terrón-Camero Laura C , Peláez-Vico M Ángeles , Molina-Moya Eliana , Sandalio Luisa M
Published: June 2021

Complex signalling pathways are involved in plant protection against single and combined stresses. Plants are able to coordinate genome-wide transcriptional reprogramming and display a unique programme of transcriptional responses to a combination of stresses that differs from the response to single stresses. However, a significant overlap between pathways and some defence genes in the form of shared and general stress-responsive genes appears to be commonly involved in responses to multiple biotic and abiotic stresses. Reactive oxygen and nitrogen species, as well as redox signals, are key molecules involved at the crossroads of the perception of different stress factors and the regulation of both specific and general plant responses to biotic and abiotic stresses. In this review, we focus on crosstalk between plant responses to biotic and abiotic stresses, in addition to possible plant protection against pathogens caused by previous abiotic stress. Bioinformatic analyses of transcriptome data from cadmium- and fungal pathogen-treated plants focusing on redox gene ontology categories were carried out to gain a better understanding of common plant responses to abiotic and biotic stresses. The role of reactive oxygen and nitrogen species in the complex network involved in plant responses to changes in their environment is also discussed.
A statistical and lexical study ofClavis Prophetarum[Key of the Prophets] by António Vieira, S.J. (1608–97)
Authors: Assunção Carlos , Tavares José Paulo , Fernandes Gonçalo
Published: June 2021

We applied the resources created in NooJ software, developed by Max Silberstein, to the third book of the Clavis Prophetarum [Key of the Prophets], by the 17th century Father António Vieira S.J. (1608–97), in the Latin version and its Portuguese translation by Espírito Santo, 2000, Critical Edition of the Clavis Prophetarum / Chave dos Profetas: Livro III by António Vieira. Lisboa: Biblioteca Nacional. We have carried out a statistical and lexical study that attempts to overcome the mere counting of forms, highlighting the lexical richness of texts, forms with higher frequency, new forms, and lexical associations. We created Nooj dictionaries for specific purposes and local grammars that allowed an analysis of the Latin text and its translation into Portuguese, going beyond mere counts of forms and highlighting the vocabulary richness of both texts, the most frequent forms, the new forms, and the lexical associations. This contrastive analysis has shown, for example, that, contrary to what one might expect, the Latin lexicon of the Latin original text is richer than the Portuguese translation.
Semiotically-grounded distant viewing of diagrams: insights from two multimodal corpora
Authors: Hiippala Tuomo , Bateman John A
Published: June 2021

In this article, we argue for the benefits of combining large-scale analyses of visual materials currently pursued within digital humanities with insights from multimodality research, which is an emerging discipline that studies how human communication relies on appropriate combinations of expressive resources. We show that concepts developed within the field of multimodality research provide appropriate metadata schemes for various modes of expression in large corpora and datasets. We illustrate the proposed approach using a common mode of expression, diagrams, and analyse two recent multimodal diagram corpora using statistical and computational methods. Our results suggest that multimodally-motivated metadata schemes can provide a robust foundation for computational analyses of large corpora and datasets. Even if a corpus or dataset is not designed to support full-blown analyses of multimodal communication, our results imply that multimodality theory can still be used to impose tighter analytical control over a variety of visual materials.
Structural basis of Staphylococcus aureus Cas9 inhibition by AcrIIA14
Authors: Liu Hongnan , Zhu Yuwei , Lu Zebin , Huang Zhiwei
Published: June 2021

Bacteriophages have evolved a range of anti-CRISPR proteins (Acrs) to escape the adaptive immune system of prokaryotes, therefore Acrs can be used as switches to regulate gene editing. Herein, we report the crystal structure of a quaternary complex of AcrIIA14 bound SauCas9–sgRNA–dsDNA at 2.22 Å resolution, revealing the molecular basis for AcrIIA14 recognition and inhibition. Our structural and biochemical data analysis suggest that AcrIIA14 binds to a non-conserved region of SauCas9 HNH domain that is distinctly different from AcrIIC1 and AcrIIC3, with no significant effect on sgRNA or dsDNA binding. Further, our structural data shows that the allostery of the HNH domain close to the substrate DNA is sterically prevented by AcrIIA14 binding. In addition, the binding of AcrIIA14 triggers the conformational allostery of the HNH domain and the L1 linker within the SauCas9, driving them to make new interactions with the target-guide heteroduplex, enhancing the inhibitory ability of AcrIIA14. Our research both expands the current understanding of anti-CRISPRs and provides additional culues for the rational use of the CRISPR-Cas system in genome editing and gene regulation.
Epidemiology, thrombolytic management, and outcomes of acute stroke among patients with chronic kidney disease: a systematic review and meta-analysis
Authors: Zamberg Ido , Assouline-Reinmann Marie , Carrera Emmanuel , Sood Manish M , Sozio Stephen M , Martin Pierre-Yves , Mavrakanas Thomas A
Published: June 2021

Background

The relative frequency of ischaemic versus haemorrhagic stroke among patients with chronic kidney disease (CKD) has not been clearly described. Moreover, no recent meta-analysis has investigated the outcomes of patients with CKD treated with thrombolysis for acute ischaemic stroke. We conducted a systematic review and meta-analysis to estimate the proportion of stroke subtypes and the outcomes of thrombolysis in CKD.

Methods

A PubMed, EMBASE and Cochrane literature research was conducted. The primary outcome was the proportion and incidence of ischaemic versus haemorrhagic strokes among patients with CKD. In addition, we assessed the impact of CKD on disability, mortality and bleeding among patients with acute ischaemic stroke treated with thrombolysis. The pooled proportion and the risk ratio were estimated using a random-effects model.

Results

Thirty-nine observational studies were included: 22 on the epidemiology of stroke types and 17 on the outcomes of thrombolysis in this population. In the main analysis (>99 281 patients), ischaemic stroke was more frequent than haemorrhagic among patients with CKD [78.3%, 95% confidence interval (CI) 73.3–82.5%]. However, among patients with kidney failure, the proportion of ischaemic stroke decreased and was closer to that of haemorrhagic stroke (59.8%, 95% CI 49.4–69.4%). CKD was associated with worse clinical outcomes in patients with acute ischaemic stroke compared with patients with preserved kidney function.

Conclusions

The relative frequency of haemorrhagic stroke seems to increase as kidney function declines. Among patients with acute ischaemic stroke treated with thrombolysis, presence of CKD is associated with higher disability, mortality and bleeding, compared with patients with preserved kidney function.
Women scientists in China: current status and aspirations
Authors: Gu Chao
Published: June 2021

Throughout history, gender inequality has persisted in most parts of the world. Since the founding of the People's Republic of China (PRC) in 1949, substantial progress has been made towards gender equality in China. Today, a large number of Chinese women scientists are making significant contributions to advance science. However, are they facing gender discrimination in hiring and promotion? Do they have access to the same opportunities as their male colleagues? What are the potential approaches to further promote gender equality in China's scientific community given myriad unfavorable social factors? Recently, NSR invited five Chinese female scientists and two gender experts to discuss these issues. Here are their observations and suggestions.

Bing Liu

Professor at the Department of the History of Science, Tsinghua University

Jun Lu

Senior Engineer at Beijing Institute of Tracking and Telecommunications Technology, and Deputy Chief Designer of BeiDou Grounded Test and Validation System

Chih-chen Wang

Professor at the Institute of Biophysics, Chinese Academy of Sciences

Hongyang Wang

President of the China Women's Association for Science and Technology (CWAST), Director of the National Center for Science in Liver Cancer

Xiaoyun Wang

C. N. Yang Professor at the Institute for Advanced Study, Tsinghua University

Yan Zheng

Chair Professor at the School of Environmental Science and Engineering, Southern University of Science and Technology

Wenpei Tang (Chair)

Professor at the School of Health Humanities, Peking University
Treatment of a Giant Thrombotic M1 Segment Middle Cerebral Artery Aneurysm With Radial Artery Bypass and Distal Occlusion to Create a “Blind Sac” Following Endovascular Failure: 2-Dimensional Operative Video
Authors: Eshraghi Sheila R , Barrow Daniel L
Published: June 2021

The case is of a 36-yr-old male with a previously coiled aneurysm arising from the proximal M1 segment of the middle cerebral artery (MCA) just beyond the internal carotid artery (ICA) bifurcation who presented to our institution with subjective left hemiparesis, headache, and vomiting. Physical exam revealed a left facial droop, but neurological exam was otherwise normal, including full motor strength. Neuroimaging showed a large partially thrombosed aneurysm recurrence, measuring 5.2 cm, with obstructive hydrocephalus. Cerebral angiogram showed filling within a small portion of the aneurysm and marked stenosis of the MCA beyond the neck. A ventriculostomy was placed, and he underwent a pterional craniotomy for high-flow radial artery bypass from the common carotid artery to an M2 branch of the MCA and clip placement. This case demonstrates the creation of a blind sac by placing a clip on the MCA distal to the aneurysm and proximal to the lenticulostriate arteries for the treatment of a giant proximal M1 segment aneurysm. Postoperative digital subtraction angiography shows the MCA distribution, including the lenticulostriate arteries, filling through the radial artery bypass, and anterograde flow through the ICA, which perfuses up to and including the anterior choroidal artery. There is no residual filling of the aneurysm. The patient remained at his neurological baseline postoperatively and required ventriculoperitoneal shunt placement for hydrocephalus. At outpatient follow-up, computed tomography imaging showed decreased size of the thrombosed aneurysm, measuring 4.5 cm, and he had no neurological deficits. The patient gave informed consent for surgery and deidentified video recording of this case.
Microsurgical Clip Trapping of Dorsal Internal Carotid Artery Blister Ruptured Aneurysm: 2-Dimensional Operative Video
Authors: Khan Nickalus R , Elarjani Turki , Cajigas Ian , Chen Stephanie , Morcos Jacques J
Published: June 2021

Dorsal internal carotid artery (ICA) blister aneurysms are an uncommon aneurysm variant constituting 0.3% to 1% of intracranial aneurysms and can be due to ulceration, atherosclerosis, or dissection.
1-3
Despite its rarity, it carries a high risk of rupture with an estimation of 0.9% to 6.5% among intracranial aneurysms.
1,2
Blister aneurysms are small in size, have no distinguishable neck, and have a friable wall that can easily rupture if manipulated, hence the difficulty in its treatment utilizing both microsurgical and endovascular techniques.
1,2,4-6
Endovascular coiling of these lesions may not be adequate due to the broad-based size; stenting requires the use of antiplatelet medications, which could lead to rebleeding; flow diversion takes longer to exert its treatment effect.
1,4
Conversely, microsurgical management carries a higher intraoperative rupture rate.
2
Microsurgical options include clipping, clip reconstruction, trapping with bypass, and wrapping.
4,7
We present a case of a 38-yr-old man who presented with a ruptured right dorsal ICA blister aneurysm treated with microsurgical trapping with intraoperative flow measurements. We demonstrate how the use of quantitative intraoperative flow measurements allows confident sacrifice of the supraclinoid ICA. We also demonstrate in contrast another case example of utilizing a clip-graft repair. The patient remained unchanged with an intact neurological exam, and postoperative imaging showed no aneurysm remnant and patent anterior choroidal artery. We review the literature and management of dorsal ICA aneurysms.
8-15
We also review the technical nuances and different endovascular and microsurgical treatments that can be used for this condition.

 The patient gave informed consent for the procedure and verbal consent to the publication.
New method of screening for COVID-19 disease using sniffer dogs and scents from axillary sweat samples
Authors: Sarkis Riad , Lichaa Anthony , Mjaess Georges , Saliba Michele , Selman Carlo , Lecoq-Julien Clothilde , Grandjean Dominique , Jabbour Nabil M
Published: June 2021

Background

Early screening for COVID-19 is needed to limit the spread of the virus. The aim of this study is to test if the sniffer dogs can be successfully trained to identify subjects with COVID-19 for ‘proof of concept’ and ‘non-inferiority’ against PCR. We are calling this method, Dognosis (DN).

Methods

Four hundred and fifty-nine subjects were included, 256 (Group ‘P’) were known cases of COVID-19 (PCR positive, some with and some without symptoms) and 203 (Group ‘C’) were PCR negative and asymptomatic (control). Samples were obtained from the axillary sweat of each subject in a masked fashion. Two dogs trained to detect specific Volatile Organic Compounds for COVID-19 detection were used to test each sample.

Results

[DN] turned out positive (+) in all the cases that were PCR positive (100% sensitivity). On the other hand, [DN] turned positive (+) in an average of 12.5 cases (6.2%) that were initially PCR negative (apparent specificity of 93.8%). When the PCR was repeated, true specificity was 97.2%. These parameters varied in subgroups from 100% sensitivity and 99% specificity in symptomatic patients to 100% sensitivity and 93% specificity in asymptomatic patients.

Conclusion

DN method shows high sensitivity and specificity in screening COVID-19 patients.
Nudge me: tailoring text messages for prescription adherence through N-of-1 interviews
Authors: Waughtal Joy , Luong Phat , Sandy Lisa , Chavez Catia , Ho P Michael , Bull Sheana
Published: June 2021

Almost 50% of patients with cardiovascular diseases face challenges in taking medications and increased morbidity and mortality. Text messaging may impact medication refill behavior and can be delivered at scale to patients by texting mobile phones. To obtain feedback from persons with chronic conditions on the design of interactive text messages and determine language of message for making messages that can motivate patients to refill medications on time. We purposively sampled 35 English and Spanish speaking patients with at least one chronic condition from three large healthcare delivery systems to participate in N-of-1 video-based synchronous interviews. Research assistants shared ideas for theory-informed text messages with content intended to persuade patients to refill their medication. We transcribed recorded interviews and conducted a content analysis to identify strategies to employ generating a dynamic interactive text message library intended to increase medication refill. Those interviewed were of diverse age and race/ethnicity and typical of persons with multiple chronic conditions. Several participants emphasized that personally tailored and positively framed messages would be more persuasive than generic and/or negative messages. Some patients appreciated humor and messages that could evoke a sense of social support from their providers and rejected the use of emojis. Messages to remind patients to refill medications may facilitate improvements in adherence, which in turn can improve chronic care. Designing messages that are persuasive and can prompt action is feasible and should be considered given the ease with which such messages can be delivered automatically at scale.
Predictors of medical mistrust among urban youth of color during the COVID-19 pandemic
Authors: Ash Marcia J , Berkley-Patton Jannette , Christensen Kelsey , Haardörfer Regine , Livingston Melvin D , Miller Teesha , Woods-Jaeger Briana
Published: June 2021

The COVID-19 pandemic has disproportionately impacted communities of color and highlighted longstanding racial health inequities. Communities of color also report higher rates of medical mistrust driven by histories of medical mistreatment and continued experiences of discrimination and systemic racism. Medical mistrust may exacerbate COVID-19 disparities. This study utilizes the Behavior Model for Vulnerable Populations to investigate predictors of medical mistrust during the COVID-19 pandemic among urban youth of color. Minority youth (N = 105) were recruited from community organizations in Kansas City, Missouri to complete an online survey between May and June 2020. Multiple linear regressions were performed to estimate the effect of personal characteristics, family and community resources, and COVID-19 need-based factors on medical mistrust. Results indicated that loneliness, financial insecurity (e.g., job loss, loss of income) due to the COVID-19 pandemic, and eligibility for free or reduced lunch predicted medical mistrust. Insurance status, neighborhood median household income, social support, and perceived COVID-19 risk were not significantly associated with medical mistrust. Future research and policies are necessary to address systemic factors that perpetuate medical mistrust among youth of color.
Tandem Protein Kinases Emerge as New Regulators of Plant Immunity
Authors: Klymiuk Valentyna , Coaker Gitta , Fahima Tzion , Pozniak Curtis J.
Published: June 2021

Plant–pathogen interactions result in disease development in a susceptible host. Plants actively resist pathogens via a complex immune system comprising both surface-localized receptors that sense the extracellular space as well as intracellular receptors recognizing pathogen effectors. To date, the majority of cloned resistance genes encode intracellular nucleotide-binding leucine-rich repeat receptor proteins. Recent discoveries have revealed tandem kinase proteins (TKPs) as another important family of intracellular proteins involved in plant immune responses. Five TKP genes—barley Rpg1 and wheat WTK1 (Yr15), WTK2 (Sr60), WTK3 (Pm24), and WTK4—protect against devastating fungal diseases. Moreover, a large diversity and numerous putative TKPs exist across the plant kingdom. This review explores our current knowledge of TKPs and serves as a basis for future studies that aim to develop and exploit a deeper understanding of innate plant immunity receptor proteins.

[Formula: see text] Copyright © 2021 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license .
Hepatocyte‐specific depletion of augmenter of liver regeneration (ALR) protein alters miRNA signature linked to lipid homeostasis leading to excessive steatosis
Authors: Kumar Sudhir , Rani Richa , Karns Rebekah , Sharma Bal Krishan , Gandhi Chandrashekhar R.
Published: June 2021

Augmenter of liver regeneration (ALR) is a fundamental life protein expressed in all mammalian organs. ALR's presence in mitochondria is essential for their function and survival. Depletion of ALR from liver (hepatocyte)‐specific ALRflox/flox/Alb‐Cre (ALR‐L‐KO) mice causes mitochondrial injury, robust lipid accumulation and apoptosis between 1 and 2 weeks post‐birth. Steatosis is regressed upon reappearance of ALR by 4 weeks but continued death of Cre‐expressing hepatocytes induces regeneration, inflammation and fibrosis. To delineate mechanisms of this pathological progression, we investigated whether ALR depletion alters expression of micro‐RNAs (miRNAs), which play important roles in numerous biological processes including lipid homeostasis. We performed miRNA‐seq analysis and profiled the hepatic miRNA expression in 1‐, 2‐, and 4‐week old mice. Of the 765 micro‐RNAs identified in WT and ALR‐L‐KO livers, 203 showed differential expression: 125, 106 and 141 miRNAs were up‐regulated and 70, 97 and 61 miRNAs down‐regulated at 1, 2 and 4 weeks respectively in ALR‐L‐KO compared to the WT mice. miR‐708‐3p, miR‐540‐3p and miR‐541‐5p, which have 3′UTR‐binding sites for peroxisome proliferator‐activated receptor (PPAR)α, carnitine palmitoyl transferase a (CPT1a) and mitochondrial transcription factor A (TFAM) (all down‐regulated at 2 weeks in ALR‐L‐KO mice), were all found to be up‐regulated at 2 weeks in ALR‐L‐KO compared to the WT mice. Increase in these miRNAs upon ALR depletion was also concurrent with increased expression of elongation of very long fatty acids 6 (ELOVl6) and steroyl CoA desaturase (SCD1) that are involved in de novo lipogenesis, and decreased expression of acyl CoA oxidase 1 (ACOX1) and CPT1 that promote β‐oxidation of fatty acids. The effect of ALR depletion on these miRNAs was recapitulated in vitro in cultured hepatocytes. Likewise, hepatic expression of miRNAs implicated in inflammation and fibrosis (miR‐199a‐1‐5p, miR‐146b‐5p, miR‐194‐1‐5p, miR‐1843a, miR‐410‐3p and miR‐434‐3p) was also altered in a way to promote these pathologies. These findings suggest that ALR's regulation of miRNAs is critical to hepatic lipid homeostasis with potential implications in nonalcoholic fatty liver disease/steatohepatitis.

Support or Funding Information

This work was supported by DoD grant W81XWH‐14‐PRMRP‐IIRA and NIH R21 AA020846 to CRG.

This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Anatomical and functional landscapes of hair regeneration across the body
Authors: Plikus Maksim , Wang Qixuan , Oh Ji Won , Nie Qing
Published: June 2021

Hair follicles (HFs) in the skin show robust cyclic regeneration. Yet, since skin contains many thousands of HFs, control principles of collective hair regeneration and hair growth regionalization remain unclear. Using multi‐scale mathematical modeling we shows that coupling inhibitor and activator signals with physical growth of HFs is sufficient to drive periodicity and excitability of hair regeneration. Model simulations and experimental data reveal that the entire skin in mice behaves as a heterogeneous regenerative landscape, composed of anatomical domains where HFs have distinct cycling dynamics. Interactions between fast‐cycling ventral and chin HFs and slow‐cycling dorsal HFs produce prominent bilaterally symmetric patterns. Skin on mouse ears behaves as a hyper‐refractory domain with HFs that remain, in principle, competent to cyclic regeneration, yet that physiologically enter extended rest phase. Ear HF hyper‐refractivity relates to high levels of BMP ligands and WNT antagonists, in part expressed by ear‐specific cartilage and muscle, the novel component of skin signaling macro‐environment. Hair growth stops at the boundaries with hyper‐refractory ears and anatomically discontinuous eyelids, generating wave‐breaking effects. We posit that similar mechanisms for coupled regeneration and large‐scale patterning of growth activities with dominant activator, hyper‐refractory, and wave‐breaker regions can operate in other actively renewing organs.

Support or Funding Information

MVP is supported by the NIH NIAMS grants R01‐AR067273, R01‐AR069653 and Pew Charitable Trust grant. QN is supported by NSF grants: DMS 1161621, and DMS 1562176 and NIH grants: P50‐GM076516, R01‐GM107264, and R01‐NS095355. JWO is supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIP) (2016R1C1B1015211).

This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
TRPV4 channels regulates matrix stiffness and TGFβ1‐induced epithelial‐mesenchymal transition
Authors: Rahaman Shaik O. , Sharma Shweta , Goswami Rishov
Published: June 2021

Epithelial‐mesenchymal transition (EMT) has important functions in cellular processes including development, wound healing, oncogenesis, and fibrosis. Emerging data support a role for both a mechanical signal, and a biochemical signal, e.g., transforming growth factor β1 (TGFβ1), in EMT. Here, we report evidence showing that transient receptor potential vanilloid 4 (TRPV4), calcium‐permeable channel and member of TRP superfamily, is the likely mediator of EMT in response to both TGFβ1 and matrix stiffness. Specifically, we found that: i) genetic ablation of TRPV4 blocked TGFβ1‐induced EMT in normal mouse primary epidermal keratinocytes (NMEKs) as determined by changes in morphology and alterations of expression of EMT markers including E‐cadherin (ECAD), N‐cadherin (NCAD), and α‐smooth muscle actin (α‐SMA), and ii) TRPV4 deficiency prevented matrix stiffness‐induced EMT in NMEKs over a pathophysiological range. Intriguingly, TRPV4 deletion in mice suppressed expression of mesenchymal markers, NCAD and α‐SMA, in a bleomycin‐induced murine skin fibrosis model. We found an increased co‐localization of TRPV4 with NCAD, and decreased co‐localization of TRPV4 with epithelial marker ECAD in skin tissues of bleomycin‐treated wild‐type mice compared to saline controls. Mechanistically, we found that: i) TRPV4 was essential for the nuclear translocation of YAP/TAZ (Yes‐associated protein/transcriptional coactivator with PDZ‐binding motif) in response to matrix stiffness and TGFβ1, ii) TRPV4 deletion inhibited both matrix stiffness‐ and TGFβ1‐induced expression of YAP/TAZ proteins, and iii) TRPV4 deletion abrogated both matrix stiffness‐ and TGFβ1‐induced activation of AKT, but not Smad2/3, suggesting a mechanism by which TRPV4 activity regulates EMT in NMEKs. Altogether, these data identify a novel role for TRPV4 in regulating EMT, and thus suggest that therapeutic targeting of TRPV4 may provide a selective approach to ameliorate the development of skin fibrosis and oncogenesis.

Support or Funding Information

AHA (13SDG17310007), Startup grant from University of Maryland, NIH (1R01EB024556‐01), and NSF (CMMI‐1662776) grants to SOR.

This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Cell cycle re‐entry from quiescence promotes genome instability
Authors: Matson Jacob P. , Limas Juanita , Perez Joanna , Kedziora Kasia , Cook Jeannette G.
Published: June 2021

Animal cells transition between periods of active cell division cycles and periods of quiescence without cell division. Prior to cell division, DNA replication initiates at thousands of origins across the genome during S phase of every cell cycle. Each origin that initiates must have been licensed for replication in the preceding G1 phase by the regulated loading of Minichromosome maintenance (MCM) complexes onto DNA. Cells with insufficient MCM loading are underlicensed, risk incomplete replication, and are hypersensitive to replication stress and DNA damage. Licensing is tightly restricted to G1 phase, but the length of G1 varies. How mammalian cells ensure sufficient licensing in cells with either long or short G1 phases is still poorly understood. We recently reported that cycling cells with naturally short G1 phases license origins faster than cells with long G1s and that the fast loading is important for a short G1. The first G1 phase of cells re‐entering the cell cycle from quiescence is longer than G1 phase in actively cycling cells. We hypothesized that the differences in G1 length during cell cycle re‐entry and G1 length in dividing cells will result in differences in the amount or rate of origin licensing in the different G1 phases. We used single cell flow cytometry and live cell imaging to explore the relationships among cell cycle re‐entry, G1 length, origin licensing, and the activity of the family of cyclin‐dependent kinases that drive the G1‐to‐S phase transition in untransformed human cells. Despite the extra time in G1 phase, cells re‐entering the cell cycle are significantly underlicensed in the first cell cycle but not the second or subsequent cell cycles. Moreover, cells in the first S phase are hypersensitive to replication stress. Thus, G1 phase upon cell cycle re‐entry is characterized by slow (or delayed) origin licensing combined with S phase entry before all cells are fully licensed. Overproducing cyclin E or cyclin A can uncouple G1 length from origin licensing by driving premature S phase entry. We predict that the normal coupling of origin licensing and Cdk2 activation is weaker at the first G1/S transition. Cells re‐entering the cell cycle from quiescence have increased levels of Cdk inhibitor proteins which may contribute to the uncoupling of licensing timing or speed and S phase entry. The transition from quiescence to active division is a particularly sensitive time for DNA damage and the number of transitions into and out of quiescence may play a role in long term cell viability and genome stability.

Support or Funding Information

This work was supported by a fellowship from the NSF (DGE‐1144081) to J.P.M and by the NIH to J.G.C. (GM083024 and GM102413). Additional funding was provided by the W.M. Keck Foundation.

This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.