bluuebunny/crossref_metadata_2025 huggingface dataset:
Anticentromere Antibody Levels and Isotypes and the Development of Systemic Sclerosis
Authors: van Leeuwen Nina M. , Boonstra Maaike , Bakker Jaap A. , Grummels Annette , Jordan Suzana , Liem Sophie , Distler Oliver , Hoffmann‐Vold Anna‐Maria , Melsens Karin , Smith Vanessa , Truchetet Marie‐Elise , Scherer Hans U. , Toes René , Huizinga Tom W. J. , de Vries‐Bouwstra Jeska K.
Published: May 2021

Objective

Little is known on the disease course of very early systemic sclerosis (SSc). Among the information yet to be elucidated is whether anticentromere antibody (ACA) isotype levels can serve as biomarkers for future SSc development and for organ involvement. This study was undertaken to evaluate whether IgG, IgM, and IgA ACA levels in IgG ACA–positive patients are associated with disease severity and/or progression from very early SSc to definite SSc.

Methods

IgG ACA–positive patients from 5 different cohorts who had very early SSc or SSc fulfilling the American College of Rheumatology (ACR)/European Alliance of Associations for Rheumatology (EULAR) 2013 criteria were included. A diagnosis of very early SSc was based on the presence of IgG ACAs and Raynaud’s phenomenon, and/or puffy fingers and/or abnormal nailfold capillaroscopy, but not fulfilling the ACR/EULAR 2013 criteria for SSc. Multivariable regression analyses were performed to determine the association between baseline ACA isotype levels and progression to definite SSc with organ involvement.

Results

Six hundred twenty‐five IgG ACA–positive patients were included, of whom 138 (22%) fulfilled the criteria for very early SSc and 487 (78%) had definite SSc. Levels of IgG ACAs (odds ratio 2.5 [95% confidence interval 1.8–3.7]) and IgM ACAs (odds ratio 1.8 [95% confidence interval 1.3–2.3]) were significantly higher in patients with definite SSc. Of 115 patients with very early SSc with follow‐up, progression to definite SSc occurred within 5 years in 48 (42%). Progression to definite SSc was associated with higher IgG ACA levels at baseline (odds ratio 4.3 [95% confidence interval 1.7–10.7]).

Conclusion

ACA isotype levels may serve as biomarkers to identify patients with very early SSc who are at risk for disease progression to definite SSc.
Examination of the effect of curcumin in experimental liver damage created by diethylnitrosamine in Swiss albino mice to superoxide dismutase and catalase activities and glutathione, malondialdehyde, and advanced oxidation protein products levels
Authors: Seriner Ramazan , Dağlıoğlu Kenan , Coşkun Gülfidan , Bilgin Ramazan
Published: May 2021

In this study, the effects of curcumin, glutathione (GSH), malondialdehyde (MDA) levels, advanced protein oxidation products (AOPP), superoxide dismutase (SOD), and catalase (CAT) activities in experimental liver damage with diethylnitrosamine (DEN) in Swiss albino mice were investigated. The subjects (n = 9) used in the study were divided into 5 groups as tumor control 1, tumor control 2, curcumin protective, curcumin treatment and healthy control groups Curcumin oral gavage (in 150 mg/kg of ethylalcohol) was given to the protecting group for 19 days, 5 days before the administration of DEN, and 24 h after the administration of DEN. Hundred microliters of ethylalcohol oral gavage was given to the healthy group for 19 days. While MDA levels decreased significantly in the curcumin preservative group (p < 0.05), (p = 0.002), the decrease was not significant in the treatment groups (p > 0.05), (p = 0.128). AOPP levels decreased significantly in the curcumin protective group (p < 0.05), (p = 0.009) but the decrease in the treatment group was not found significant (p > 0.05), (p = 0.073). SOD activities increased significantly in both groups. It was found as (p < 0.05), (p = 0.001) and (p < 0.05), (p = 0.002), respectively. GSH levels decreased but these reductions were not found statistically significant. CAT activities increased significantly in both groups. It was determined as (p < 0.05), (p = 0.001) for both groups.
Adult age differences in monetary decisions with real and hypothetical reward
Authors: Horn Sebastian , Freund Alexandra M.
Published: May 2021

Age differences in monetary decisions may emerge because younger and older adults perceive the value of outcomes differently. Yet, age‐differential effects of monetary rewards on decisions are not well understood. Most laboratory studies on aging and decision making have used scenarios in which rewards were merely hypothetical (decisions did not have any real consequences) or in which only small amounts of money were at stake. In the current study, we compared younger adults' (20–29 years) and older adults' (61–82 years) decisions in probabilistic choice problems with real or hypothetical rewards. Decision‐contingent rewards were in a typical range of previous studies (gains of up to ~4.25 USD) or substantially scaled up (gains of up to ~85 USD per participant). Reward type (real vs. hypothetical) affected decision quality, including value maximization, switching between options, and dominance violations (choices of an option that was inferior to another option in all respects). Decision quality was markedly better with real than hypothetical rewards in older adults and correlated with numeracy in both age groups. However, we found no evidence that reward type affected people's risk preferences. Overall, the findings portray a fairly positive picture regarding the use of hypothetical scenarios to assess preferences: With carefully prepared instructions, people from different age groups indicate preferences in hypothetical scenarios that match their decisions with real and much higher rewards. One advantage of using real rewards is that they help to reduce decision noise.
Spectrum–effect relationship between high‐performance thin‐layer chromatography data and xanthine oxidase inhibitory activity of celery seed extract
Authors: Thu Hang Nguyen , Viet Hoang Le , Van Phuong Nguyen
Published: May 2021

Celery seeds are medicinal herbs used for the prevention and treatment of gout as these have the ability to inhibit the activity of xanthine oxidase and reduce the concentration of serum uric acid. In this study, the relationship between xanthine oxidase inhibitory effects and high‐performance thin‐layer chromatography data of celery seed extracts was established using multilayer neural network (MNN) in combination with principal component analysis (PCA). The constructed MNN–PCA model was stable and had accurate prediction ability with coefficient of determination = 0.9998, leave‐one‐out coefficient = 0.7371, root mean square error = 0.0025, and mean absolute deviation = 0.0019 for the training set and coefficient of determination = 0.8124, root mean square error = 0.0784, and mean absolute deviation = 0.0645 for the test set. This model can be used to identify the main compounds related to the xanthine oxidase inhibitory effect of celery seed extract. These results can be applied not only to celery extract but also to other herbal medicines.
NOTCH3 limits the epithelial–mesenchymal transition and predicts a favorable clinical outcome in esophageal cancer
Authors: Matsuura Norihiro , Tanaka Koji , Yamasaki Makoto , Yamashita Kotaro , Saito Takuro , Makino Tomoki , Yamamoto Kazuyoshi , Takahashi Tsuyoshi , Kurokawa Yukinori , Nakajima Kiyokazu , Eguchi Hidetoshi , Nakagawa Hiroshi , Doki Yuichiro
Published: May 2021

Background

Esophageal squamous cell carcinoma (ESCC) is the deadliest of all human squamous cell carcinomas and is characterized by chemotherapy resistance and poor prognosis associated with the epithelial–mesenchymal transition (EMT). A subset of ESCC displays loss‐of‐function mutations in genes encoding Notch receptor family members, including NOTCH3. Although Notch signaling regulates EMT in ESCC cells, the role of NOTCH3 in EMT and chemotherapy resistance remains elusive. This study aimed to examine the role of NOTCH3 in EMT and chemotherapy resistance, and determine whether NOTCH3 expression can be used to predict the response to chemotherapy.

Methods

In vitro and in vivo assays were conducted to clarify the contribution of NOTCH3 to chemotherapy resistance. Using specimens from 120 ESCC patients treated with neoadjuvant chemotherapy, we compared the expression levels of NOTCH3 and genes involved in EMT according to the degree of chemotherapy sensitivity.

Results

In ESCC cells, chemotherapy resistance was associated with NOTCH3 downregulation and concurrent activation of EMT. RNA interference to silence NOTCH3 resulted in induction of the EMT marker Vimentin (VIM), leading to chemotherapy resistance in ESCC cells. Conversely, ectopic expression of the activated form of NOTCH3 suppressed EMT and sensitized cells to chemotherapy. Results of chromatin immunoprecipitation assays suggested that NOTCH3 may repress transcription of the VIM.

Conclusions

Our findings suggest that NOTCH3 may control chemotherapy sensitivity by regulating EMT. NOTCH3 may serve as a novel biomarker to predict better clinical outcomes in ESCC patients.
Recent Advances in Bioactive Artificial Ionophores
Authors: Roy Arundhati , Talukdar Pinaki
Published: May 2021

Several life‐threatening diseases, also known as ‘Channelopathies’ are linked to irregularities in ion transport proteins. Significant research efforts have fostered the development of artificial transport systems that facilitates to restore the functions of impaired natural transport proteins. Indeed, a few of these artificial ionophores demonstrate the rare combination of transmembrane ion transport and important biological activity, offering early promises of suitability in ‘channel replacement therapy’. In this review, structural facets and functions of both cationophores and anionophores are discussed. Ionophores that are toxic to various bacteria and yeast, could be exploited as antimicrobial agent. Nevertheless, few non‐toxic ionophores offer the likelihood of treating a wide range of genetic diseases caused by the gene mutations. In addition, their ability to disrupt cellular homeostasis and to alter lysosomal pH endow ionophores as promising candidates for cancer treatment. Overall, critically outlining the advances in artificial ionophores in terms of in vitro ion transport, possible modes of action and biological activities enables us to propose possible future roadmaps in this research area.
Strategies for Covalent Labeling of Long RNAs
Authors: Depmeier Hannah , Hoffmann Eva , Bornewasser Lisa , Kath‐Schorr Stephanie
Published: May 2021

The introduction of chemical modifications into long RNA molecules at specific positions for visualization, biophysical investigations, diagnostic and therapeutic applications still remains challenging. In this review, we present recent approaches for covalent internal labeling of long RNAs. Topics included are the assembly of large modified RNAs via enzymatic ligation of short synthetic oligonucleotides and synthetic biology approaches preparing site‐specifically modified RNAs via in vitro transcription using an expanded genetic alphabet. Moreover, recent approaches to employ deoxyribozymes (DNAzymes) and ribozymes for RNA labeling and RNA methyltransferase based labeling strategies are presented. We discuss the potentials and limits of the individual methods, their applicability for RNAs with several hundred to thousands of nucleotides in length and indicate future directions in the field.
Pharmacogenetics of Bleeding and Thromboembolic Events in Direct Oral Anticoagulant Users
Authors: Lähteenmäki Jaakko , Vuorinen Anna‐Leena , Pajula Juha , Harno Kari , Lehto Mika , Niemi Mikko , van Gils Mark
Published: May 2021

This study aimed to analyze associations between genetic variants and the occurrence of clinical outcomes in dabigatran, apixaban, and rivaroxaban users. This was a retrospective real‐world study linking genotype data of three Finnish biobanks with national register data on drug dispensations and healthcare encounters. We investigated several single‐nucleotide variants (SNVs) in the ABCG2, ABCB1, CES1, and CYP3A5 genes potentially associated with bleeding or thromboembolic events in direct oral anticoagulant (DOAC) users based on earlier research. We used Cox regression models to compare the incidence of clinical outcomes between carriers and noncarriers of the SNVs or haplotypes. In total, 1,806 patients on apixaban, dabigatran, or rivaroxaban were studied. The ABCB1 c.3435C>T (p.Ile1145=, rs1045642) SNV (hazard ratio (HR) 0.42, 95% confidence interval (CI), 0.18–0.98, P = 0.044) and 1236T‐2677T‐3435T (rs1128503‐rs2032582‐rs1045642) haplotype (HR 0.44, 95% CI, 0.20–0.95, P = 0.036) were associated with a reduced risk for thromboembolic outcomes, and the 1236C‐2677G‐3435C (HR 2.55, 95% CI, 1.03–6.36, P = 0.044) and 1236T‐2677G‐3435C (HR 5.88, 95% CI, 2.35–14.72, P < 0.001) haplotypes with an increased risk for thromboembolic outcomes in rivaroxaban users. The ABCB1 c.2482‐2236G>A (rs4148738) SNV associated with a lower risk for bleeding events (HR 0.37, 95% CI, 0.16–0.89, P = 0.025) in apixaban users. ABCB1 variants are potential factors affecting thromboembolic events in rivaroxaban users and bleeding events in apixaban users. Studies with larger numbers of patients are warranted for comprehensive assessment of the pharmacogenetic associations of DOACs and their relevance for clinical practice.
Differential transcriptional and functional properties of regulatory T cells in HIV‐infected individuals on antiretroviral therapy and long‐term non‐progressors
Authors: Shahbaz Shima , Jovel Juan , Elahi Shokrollah
Published: May 2021

Objectives

Regulatory T cells (Tregs) are widely recognised as a subset of CD4+CD25+FOXP3+ T cells that have a key role in maintaining immune homeostasis. The impact of HIV‐1 infection on immunological properties and effector functions of Tregs has remained the topic of debate and controversy. In the present study, we investigated transcriptional profile and functional properties of Tregs in HIV‐1‐infected individuals either receiving antiretroviral therapy (ART, n = 50) or long‐term non‐progressors (LTNPs, n = 24) compared to healthy controls (HCs, n = 38).

Methods

RNA sequencing (RNAseq), flow cytometry‐based immunophenotyping and functional assays were performed to study Tregs in different HIV cohorts.

Results

Our RNAseq analysis revealed that Tregs exhibit different transcriptional profiles in HIV‐infected individuals. While Tregs from patients on ART upregulate pathways associated with a more suppressive (activated) phenotype, Tregs in LTNPs exhibit upregulation of pathways associated with impaired suppressive properties. These observations may explain a higher propensity for autoimmune diseases in LTNPs. Also, we found substantial upregulation of HLA‐F mRNA and HLA‐F protein in Tregs from HIV‐infected subjects compared to healthy individuals. These observations highlight a potential role for this non‐classical HLA in Tregs in the context of HIV infection, which should be investigated further in other chronic viral infections and cancer.

Conclusion

Our study has provided a novel insight into Tregs at the transcriptional and functional levels in different HIV‐infected groups.
Amyloid beta associations with connected speech in cognitively unimpaired adults
Authors: Mueller Kimberly D. , Van Hulle Carol A. , Koscik Rebecca L. , Jonaitis Erin , Peters Cassandra C. , Betthauser Tobey J. , Christian Bradley , Chin Nathaniel , Hermann Bruce P. , Johnson Sterling
Published: May 2021

Introduction

Connected speech and language (CSL) decline has been associated with early cognitive decline, but associations between CSL and Alzheimer's disease (AD) biomarkers remain a gap in the literature. Our goal was to examine associations with amyloid beta (Aβ) and longitudinal CSL trajectories in cognitively unimpaired adults at increased AD risk.

Methods

Using data from the Wisconsin Registry for Alzheimer's Prevention, CSL measures were automatically extracted from digitally recorded picture descriptions. Positron emission tomography determined Aβ status. Linear mixed effects models assessed the interaction between age and Aβ on CSL trajectories.

Results

Participants who were Aβ positive experienced more rapid decline on specific word content, when controlling for age, sex, and literacy. There were no differences between groups in lexical diversity measures over time.

Discussion

These results indicate that declines in connected speech may be related to preclinical AD. CSL may be a promising, inexpensive, and easy‐to‐collect digital cognitive marker for AD studies.
Large‐scale variation in wave attenuation of oyster reef living shorelines and the influence of inundation duration
Authors: Morris Rebecca L. , La Peyre Megan K. , Webb Bret M. , Marshall Danielle A. , Bilkovic Donna M. , Cebrian Just , McClenachan Giovanna , Kibler Kelly M. , Walters Linda J. , Bushek David , Sparks Eric L. , Temple Nigel A. , Moody Joshua , Angstadt Kory , Goff Joshua , Boswell Maura , Sacks Paul , Swearer Stephen E.
Published: May 2021

One of the paramount goals of oyster reef living shorelines is to achieve sustained and adaptive coastal protection, which requires meeting ecological (i.e., develop a self‐sustaining oyster population) and engineering (i.e., provide coastal defense) targets. In a large‐scale comparison along the Atlantic and Gulf coasts of the United States, the efficacy of various designs of oyster reef living shorelines at providing wave attenuation was evaluated accounting for the ecological limitations of oysters with regard to inundation duration. A critical threshold for intertidal oyster reef establishment is 50% inundation duration. Living shorelines that spent less than one‐half of the time (<50%) inundated were not considered suitable habitat for oysters, however, were effective at wave attenuation (68% reduction in wave height). Reefs that experienced >50% inundation were considered suitable habitat for oysters, but wave attenuation was similar to controls (no reef; ~5% reduction in wave height). Many of the oyster reef living shoreline approaches therefore failed to optimize the ecological and engineering goals. In both inundation regimes, wave transmission decreased with an increasing freeboard (difference between reef crest elevation and water level), supporting its importance in the wave attenuation capacity of oyster reef living shorelines. However, given that the reef crest elevation (and thus freeboard) should be determined by the inundation duration requirements of oysters, research needs to be refocused on understanding the implications of other reef parameters (e.g., width) for optimizing wave attenuation. A broader understanding of the reef characteristics and seascape contexts that result in effective coastal defense by oyster reefs is needed to inform appropriate design and implementation of oyster‐based living shorelines globally.
The effect of species, size, and fire intensity on tree mortality within a catastrophic bushfire complex
Authors: Trouvé Raphaël , Oborne Lisa , Baker Patrick J.
Published: May 2021

Infrequent, high‐intensity disturbances can have profound impacts on forested landscapes, changing forest structure and altering relative species abundance. However, due to their rarity and the logistical challenges of directly observing such extreme events, both the spatial variability of disturbance intensity and the species‐specific responses to this variability are poorly understood. We used observed patterns of mortality across a fire severity gradient following the 2009 Black Saturday fires in southeastern Australia to simultaneously estimate (1) species‐ and size‐specific susceptibility to fire‐induced mortality and (2) fire intensity. We found broad variation in patterns of fire susceptibility among the 10 tree species (five eucalypts and five non‐eucalypts) sufficiently abundant for analysis. Among the eucalypts,Eucalyptus obliquawas the most resistant to fire‐induced mortality, with trees of ~25 cm DBH having a 50% probability of surviving even the most intense fires. In contrast,E. regnanshad 100% mortality across all size classes when subjected to high‐intensity fire. Basal resprouting occurred in six of the study species and, when accounted for, fundamentally changed the mortality profile of these species, highlighting the importance of resprouting as an adaptation to fire in these landscapes. In particular, the two iconic cool temperate rainforest species (Nothofagus cunninghamiandAtherosperma moschatum) were strong resprouters (~45% of individuals were able to resprout after being top‐killed by fire). We also found evidence for compositional shifts in regeneration above threshold values of fire intensity in cool temperate rainforest and mixed forest sites, both of which have important conservation values within these landscapes. The observed patterns of species‐ and size‐specific susceptibility to fire‐induced mortality may be used to anticipate changes in forest structure and composition in the future. In addition, they may also help guide forest management strategies that reduce the length of time individual trees are exposed to potentially lethal fires, thereby increasing the resilience of these forests to future fires.
Prognostic value of resting cardiac power index depends on mean arterial pressure in dilated cardiomyopathy
Authors: Morimoto Ryota , Mizutani Takashi , Araki Takashi , Oishi Hideo , Kimura Yuki , Kazama Shingo , Shibata Naoki , Kuwayama Tasuku , Hiraiwa Hiroaki , Kondo Toru , Furusawa Kenji , Okumura Takahiro , Murohara Toyoaki
Published: May 2021

Aims

In recent decades, haemodynamic parameters have been estimated for risk stratification and determining treatment strategies for patients with non‐ischaemic dilated cardiomyopathy (DCM). In various invasive procedures, the cardiac pumping capability is defined as cardiac power output (CPO), which is calculated by multiplying cardiac output by the mean arterial pressure. Lower CPO values in advanced heart failure predict adverse outcomes. However, few studies discuss the prognostic value of CPO in mild‐to‐moderate phase patients. This study aimed to determine the value of the cardiac power index (CPI) obtained from the resting CPO for predicting the prognosis of patients with New York Heart Association Functional Class II or III DCM.

Methods and results

From March 2000 to January 2020, a total of 623 cardiomyopathy patients were evaluated for haemodynamic parameters. Patients with secondary cardiomyopathy, ischaemic cardiomyopathy, valvular heart disease, and Class IV cardiomyopathy were excluded. A total of 176 DCM patients fulfilled the criteria for inclusion. Patients were 51.7 ± 12.5 years old (mean ± standard deviation) with a mean left ventricular ejection fraction of 32.1 ± 9.2%. The patients were divided into two groups by their median CPI (CPI < 0.52, low‐CPI; CPI ≥ 0.52, high‐CPI). No significant differences were found in the left ventricular end‐diastolic diameter, left ventricular ejection fraction, or pulmonary arterial wedge pressure between the groups. The probability of cardiac event‐free survival was significantly lower for low‐CPI than for high‐CPI groups by Kaplan–Meier analysis (P = 0.012), even with no significant difference between the high and low cardiac index groups (P = 0.069). Furthermore, Cox proportional hazards regression analysis revealed that, in addition to the CPI, the systolic and mean arterial pressure involved in CPI calculation were independent predictors of cardiac events. Indeed, among these factors, mean arterial pressure had the strongest prognostic ability.

Conclusions

Although CPI is effective for stratifying DCM and predicting cardiac events in patients with Class II/III DCM, this prognostic value depends on mean arterial pressure.
The Akt pathway mediates the protective effects of myeloid differentiation protein 1 in pathological cardiac remodelling
Authors: Peng Jianye , Zeng Gaofeng , Zhong Peng , Wang Guangji , Lei ChangCheng , Tian Guoping , Chen Jingsong , Wu Jianfeng , Shen Caijie
Published: May 2021

Aims

Myeloid differentiation protein 1 (MD1) was shown to ameliorate pressure overload‐induced cardiac hypertrophy and fibrosis by negatively regulating the MEK–ERK1/2 and NF‐κB pathways. However, whether MD1 modulates cardiac function and whether the Akt pathway mediates the benefits of MD1 in pressure overload‐induced cardiac remodelling remain unclear.

Methods and Results

Male cardiac‐specific transgenic MD1 (MD1‐TG) mice, MD1‐knockout (KO) mice and wild‐type (WT) littermates aged 8–10 weeks were subjected to sham operation and aortic banding (AB) for 4 weeks. Then, left ventricular (LV) hypertrophy, fibrosis and function of the mice were assessed. When compared with WT‐AB mice, MD1‐TGs showed decreased cross‐sectional area (CSA) of cardiomyocytes (P < 0.001), mRNA expression of β‐myosin heavy chain (β‐MHC) (P < 0.02), ratios of heart weight/body weight and heart weight/tibia length (P < 0.04) and collagen volume fraction (P < 0.001). The LV end‐diastolic diameter was reduced, and LV ejection fraction and fractional shortening were improved in MD1‐TG‐AB mice than in WT‐AB mice (P < 0.05). In cultured H9C2 cells, adenovirus vector‐mediated MD1 overexpression decreased angiotensin II‐induced mRNA expression of brain natriuretic peptide (BNP) and β‐MHC and cell CSA (P < 0.002), whereas knockdown of MD1 by shRNA exhibited opposite effects (P < 0.04). Mechanistically, MD1 suppressed pathological cardiac remodelling at least partly by blocking Akt pathway. Akt inactivation by MK2206 largely offset the pro‐hypertrophic effects of MD1 deficiency in angiotensin II‐stimulated cardiomyocytes.

Conclusions

The Akt pathway mediates the protective effects of MD1 in pressure overload‐induced cardiac remodelling in mice. Targeting MD1 may provide therapeutic strategy for the treatment of pathological cardiac remodelling and heart failure.
In the Name of Racial Justice: Why Bioethics Should Care about Environmental Toxins
Authors: Ray Keisha
Published: May 2021

Facilities that emit hazardous toxins, such as toxic landfills, oil refineries, and chemical plants, are disproportionately located in predominantly Black, Latinx, and Indigenous neighborhoods. Environmental injustices like these threaten just distribution of health itself, including access to health that is not dependent on having the right skin color, living in the right neighborhood, or making the right amount of money. Facilities that emit environmental toxins wrongly make people's race, ethnicity, income, and neighborhood essential to who is allowed to breathe clean air and drink clean water, and thus, who is allowed to be healthy. This can be seen in the environmental crises in Louisiana; Mississippi; Houston, Texas; and Flint, Michigan. Since bioethics purports to concern itself with the principle of justice as applied to individuals and increasingly to populations, the field ought to concern itself more with environmental injustice.
What Has Covid‐19 Exposed in Bioethics? Four Myths
Authors: Wolf Susan M.
Published: May 2021

The Covid‐19 pandemic has exposed four myths in bioethics. First, the flood of bioethics publications on how to allocate scarce resources in crisis conditions has assumed authorities would declare the onset of crisis standards of care, yet few have done so. This leaves guidelines in limbo and patients unprotected. Second, the pandemic's realities have exploded traditional boundaries between clinical, research, and public health ethics, requiring bioethics to face the interdigitation of learning, doing, and allocating. Third, without empirical research, the success or failure of ethics guidelines remains unknown, demonstrating that crafting ethics guidance is only the start. And fourth, the pandemic's glaring health inequities require new commitment to learn from communities facing extraordinary challenges. Without that new learning, bioethics methods cannot succeed. The pandemic is a wake‐up call, and bioethics must rise to the challenge.
Ant Cuckoo Search Optimization‐based deep learning classifier for image enhancement in spinal cord images
Authors: Saminathan Priya , Samuel Letitia
Published: May 2021

Image enhancement has been paid great attention in several areas, and various image enhancement approaches are introduced by the researchers to enhance the images clearer from the degraded images. Accordingly, this paper presents the proposed ACSO‐based IE‐CGAN for image enhancement. Initially, an effective noisy pixel identification based on image enhancement is developed, which employs circular‐based searching for improving the input image from several noises, like salt and pepper noise, speckle (impulse) noise, Gaussian noise, and random noise. Once the noisy pixels are identified, the pixel enhancement is done using the circular‐based search. The noise removal is done using a statistical model, where the best threshold value is determining using the proposed Ant Cuckoo Search Optimization (ACSO) algorithm. The ACSO algorithm is newly designed by integrating Ant Lion Optimization (ALO) and the Cuckoo Search Optimization (CSO) algorithm. After that, the contrast enhancement is carried out using Image Enhancement Conditional Generative Adversarial Network (IE‐CGAN), which is trained by the proposed ASCO algorithm. The experimentation is carried out using an osteoporotic vertebral fracture dataset, and the performance of image enhancement using ACSO‐based IE‐CGAN is evaluated based on Peak Signal to Noise ratio (PSNR), Structural Similarity Index (SSIM), and Second Derivative like Measure of Enhancement (SDME). The developed method achieves the maximal PSNR of 33.50 dB with salt and pepper noise, maximal SDME 41.38 dB with random noise, and maximal SSIM of 0.967 with salt and pepper noise.
Establishment of clinical diagnostic models using glucose, lipid, and urinary polypeptides in gestational diabetes mellitus
Authors: Hu Zhiying , Zhang Man
Published: May 2021

Background

Gestational diabetes mellitus (GDM) has many adverse outcomes that seriously threaten the short‐term and long‐term health of mothers and infants. This study comprehensively analyzed the clinical diagnostic value of GDM‐related clinical indexes and urine polypeptide research results, and established comprehensive index diagnostic models.

Methods

In this study, diagnostic values from the clinical indexes of serum triglyceride (TRIG), high‐density lipoprotein cholesterol (HDL‐C), fasting plasma glucose (FPG) and glycosylated hemoglobin (HbA1c), and 7 GDM‐related urinary polypeptides were analyzed retrospectively. The multiple logistic regression equation, multilayer perceptron neural network model, radial basis function, and discriminant analysis function models of GDM‐related indexes were established using machine language.

Results

The results showed that HbA1c had the highest diagnostic value for GDM, with an area under the curve (AUC) of 0.769. When the cut‐off value was 4.95, the diagnostic sensitivity and specificity were 70.5% and 70.0%, respectively. Among the seven GDM‐related urinary polypeptides, human hemopexin (HEMO) had the highest diagnostic value, with an AUC of 0.690. When the cut‐off value was 368.5, the sensitivity and specificity were 79.5% and 43.3%, respectively. The AUC of the multilayer perceptron neural network model was 0.942, followed by binary logistic regression (0.938), radial basis function model (0.909), and the discriminant analysis function model (0.908).

Conclusion

The establishment of a GDM diagnostic model combining blood glucose, blood lipid, and urine polypeptide indexes can lay a foundation for exploring machine language and artificial intelligence in diagnostic systems.
Dental education during the pandemic: Cross‐sectional evaluation of four different teaching concepts
Authors: Goob Janosch , Erdelt Kurt , Güth Jan‐Frederik , Liebermann Anja
Published: May 2021

Objectives

To evaluate the advantages of student satisfaction with and functionality of three digital teaching concepts during the SARS‐CoV‐2 pandemic compared to a conventional lecture setup.

Methods

This cross‐sectional study was a survey‐based e‐learning research among dental students in the clinical study phase of a department of prosthetic dentistry at a German university hospital. A total of 44 questions were answered in four main sections: 1. general technical components; 2. acceptance; 3. evaluation and functionality; and 4. overall evaluation and grades of the various digital concepts. The use of Zoom conference, livestream, and prerecorded PowerPoint was compared to the conventional lecture setup (control group/CG). Data were analyzed using the Kolmogorov‐Smirnov test, followed by an exploratory data analysis and Cronbach's alpha test (α = 0.05).

Results

Students were very satisfied with the provision, quality, and benefit of the digital concepts. The asynchronous concept was significantly more satisfying than the synchronous concepts in many aspects but was less successful in interactions. In the overall evaluation and grading, the asynchronous concept was rated significantly better than the other synchronous concepts (p ≤ 0.007), followed by Zoom conference, conventional lecture (CG), and livestream, while Zoom conference and the conventional lecture showed no significant difference (p = 0.784).

Conclusions

Students significantly preferred the asynchronous concept to the synchronous concepts. The results suggested that asynchronous concepts are an effective and functional form of distance education during a pandemic. In general, digital teaching concepts are currently widely accepted for maintaining university education.
A new D‐galactose treatment monitoring index for PGM1‐CDG
Authors: Perales‐Clemente Ester , Liedtke Kristen , Studinski April , Radenkovic Silvia , Gavrilov Dimitar , Oglesbee Devin , Matern Dietrich , Rinaldo Piero , Tortorelli Silvia , Morava Eva , Raymond Kimiyo
Published: May 2021

Phosphoglucomutase 1 (PGM1) catalyzes the interconversion of glucose‐6‐phosphate to glucose‐1‐phosphate and is a key enzyme of glycolysis, glycogenesis, and glycogenolysis. PGM1 deficiency (OMIM: 614921) was initially defined as a glycogen storage disorder (type XIV), and later re‐classified as a PGM1‐congenital disorder of glycosylation (PGM1‐CDG). Serum transferrin (Tf) glycan isoform analysis by liquid chromatography‐mass spectrometry (LC‐MS) is used as a primary diagnostic screen tool, and reveals a very unique CDG profile described as a mixture of CDG‐type I and CDG‐type II patterns. Oral d‐galactose supplementation shows significant clinical and metabolic improvements, which are indicated by the Tf glycan isoform normalization over time in patients with PGM1‐CDG. Thus, there is a need for biomarkers to guide d‐galactose dosage in patients in order to maintain effective and safe drug levels. Here, we present a simplified algorithm called PGM1‐CDG Treatment Monitoring Index (PGM1‐TMI) for assessing the response of PGM1‐CDG patients to d‐galactose supplementation. For our single‐center cohort of 16 PGM1‐CDG patients, the Tf glycan profile analysis provided the biochemical diagnosis in all of them. In addition, the PGM1‐TMI was reduced in PGM1‐CDG patients under d‐galactose supplementation as compared with their corresponding values before treatment, indicating that glycosylation proceeds towards normalization. PGM1‐TMI allows tracking Tf glycan isoform normalization over time when the patients are on d‐galactose supplementation.
Reduced serum miR‐202 may promote the progression of Alzheimer's disease patients via targeting amyloid precursor protein
Authors: Dong Li‐Hua , Sun Lei , Zhang Wen‐Jing , Wang Xiao‐Yan , Li Jia‐Mei
Published: May 2021

The current study investigated whether the expression of miR‐202 was abnormal in the serum of patients with Alzheimer's disease (AD) and evaluated the potential clinical significance, thereby shedding light on the diagnosis of AD. Here, our data showed that the level of miR‐202 decreased significantly in the serum of AD patients (n = 121) compared with that of healthy controls (n = 86). Further analysis showed that the level of serum miR‐202 was gradually decreased in the mild AD group (n = 31), moderate AD group (n = 52) and severe AD group (n = 38) compared with the healthy control group. Receiver operating characteristic (ROC) curve analysis demonstrated that serum miR‐202 could differentiate AD patients from healthy controls, with an AUC of 0.892. Spearman correlation analysis showed that serum miR‐202 was positively correlated with the Mini‐Mental State Examination (MMSE). Based on TargetScan, a conserved binding site was identified in the 3′UTR of amyloid precursor protein (APP). The dual luciferase assay showed that miR‐202 suppressed the relative luciferase activity of pmirGLO‐APP‐3′UTR. Western blot assays indicated that overexpression of miR‐202 suppressed the expression of APP, while the expression of APP was enhanced after inhibition of miR‐202 in PC12 cells, indicating that APP was a possible target gene of miR‐202. Moreover, the cell apoptosis induced by transfection of miR‐202 inhibitor was abolished by silencing APP. In summary, we showed novel data that downregulation of serum miR‐202 may be used as a potential biomarker for AD and may promote the development of AD by targeting APP.
Knockdown of ZNF479 inhibits proliferation and glycolysis of gastric cancer cells through regulating β‐catenin/c‐Myc signaling pathway
Authors: Jin Xiao‐Sheng , Ji Ting‐Ting , Shi Zheng‐Chao , Zhang Qing‐Qing , Ye Fang‐Peng , Yu Wei‐Lai , Li Rong‐Zhou
Published: May 2021

Gastric cancer is the fifth most common malignancy and the third most deadly tumor in the world. Zinc finger protein 479 (ZNF479) has been demonstrated to play crucial roles in hepatocellular carcinoma. However, the function of ZNF479 in gastric cancer remains to be clarified. The current study aimed to investigate the role of ZNF479 in gastric cancer progression and elucidate the potential molecular mechanism. In this study, Cell Count Kit‐8 and colony formation assays demonstrated that knockdown of ZNF479 inhibited cell proliferation in AGS and SGC‐7901 cells. Of note, knockdown of ZNF479 hinders tumor growth of xenograft tumor mice. What is more, knockdown of ZNF479 inhibited glucose uptake, lactate production, adenosine triphosphate level, and extracellular acidification ratio; increased oxygen consumption ratio in gastric cancer cells; and decreased the expression of glycolytic proteins both in vitro and in vivo. Furthermore, analysis mechanism suggests that ZNF479 participated in the regulation of gastric cancer progression through affecting the β‐catenin/c‐Myc signaling pathway. Collectively, ZNF479 plays a role as an oncogene through modulating β‐catenin/c‐Myc signaling pathway in the development of gastric cancer, which provides a new research target for future studies.
A Tool to Locate Parathyroid Glands Using Dynamic Optical Contrast Imaging
Authors: Hu Yong , Han Albert Y. , Huang Shan , Pellionisz Peter , Alhiyari Yazeed , Krane Jeffrey F. , Shori Ramesh , Stafsudd Oscar , St. John Maie A.
Published: May 2021

Objectives/Hypothesis

Identification of parathyroid glands and adjacent tissues intraoperatively can be quite challenging because of their small size, variable locations, and indistinct external features. The objective of this study is to test the efficacy of the dynamic optical contrast imaging (DOCI) technique as a tool in specifically differentiating parathyroid tissue and adjacent structures, facilitating efficient and reliable tissue differentiation.

Study Design

Prospective study.

Methods

Both animal and human tissues were included in this study. Fresh specimens were imaged with DOCI and subsequently processed for hematoxylin and eosin (H&E) stain. The DOCI images were analyzed and compared to the H&E results as ground truth.

Results

In both animal and human experiments, significant DOCI contrast was observed between parathyroid glands and adjacent tissue of all types. Region of interest analysis revealed most distinct DOCI values for each tissue when using 494 and 572 nm‐specific band pass filter for signal detection (P < .005 for porcine tissues, and P = .02 for human specimens). Linear discriminant classifier for tissue type prediction based on DOCI also matched the underlying histology.

Conclusions

We demonstrate that the DOCI technique reliably facilitates specific parathyroid gland localization. The DOCI technique constitutes important groundwork for in vivo precision endocrine surgery.

Level of Evidence

4 Laryngoscope, 131:2391–2397, 2021
Global asymptotic synchronization of fractional order multi‐linked memristive neural networks with time‐varying delays via discontinuous control
Authors: Wang Shaofang , Li Lixiang , Peng Haipeng , Yang Yixian , Zheng Mingwen
Published: May 2021

In this paper, we address the global asymptotic synchronization (GAS) problem of the master–slave fractional order multilinked memristive neural networks (FOMMNNs). Firstly, we propose the FOMMNNs which incorporate the fractional calculus into multilinked memristive neural networks (MMNNs) for the first time. Then, by utilizing the fractional differential inclusions and set‐valued mapping theories, the addressed FOMMNNs with discontinuous state switching at the right‐hand side and time‐varying delays are converted into the continuous FOMMNNs. Under the frameworks of fractional Caputo derivative and fractional Fillipov solution, by the way of building up appropriate Lyapunov functionals and utilizing some synchronous analysis technology, several sufficient criteria ensuring that the master–slave FOMMNNs can realize GAS under two different state‐feedback controllers are obtained. Finally, a numerical simulation is conducted to verify the effectiveness and correctness of the proposed theorems.
Mosaicism for Receptor Tyrosine Kinase Activation in a Glioblastoma Involving Both PDGFRA Amplification and NTRK2 Fusion
Authors: Shepherd Daniel J. , Miller Tyler E. , Forst Deborah A. , Jones Pamela , Nardi Valentina , Martinez-Lage Maria , Stemmer-Rachamimov Anat , Gonzalez Ramon G. , Iafrate A. John , Ritterhouse Lauren L.
Published: May 2021

Rearrangements involving the neurotrophic receptor tyrosine kinase (NTRK) gene family have been reported in diverse tumor types, and NTRK-targeted therapies have recently been approved. In this article, we report a case of a 26-year-old man with an NTRK2-rearranged isocitrate dehydrogenase-wild-type glioblastoma who showed a robust but temporary response to the NTRK inhibitor larotrectinib. Rebiopsy after disease progression showed elimination of the NTRK2-rearranged tumor cell clones, with secondary emergence of a PDGFRA-amplified subclone. Retrospective examination of the initial biopsy material confirmed rare cells harboring PDGFRA amplification. Although mosaic amplification of multiple receptor tyrosine kinase genes in glioblastoma has been previously described, mosaicism involving a fusion gene driver event has not. This case highlights the potential efficacy of NTRK-targeted treatment in glioblastoma and the implications of molecular heterogeneity in the setting of targeted therapy.

Key Points
Development of high thermally conductive and electrically insulated epoxy nanocomposites with high mechanical performance
Authors: Wang Shuo , Cai Rui , Xue Hongqian , Liu Tianqing , Han Sensen , Zhou Zhiqiang , Hu Zonghao , Meng Qingshi
Published: May 2021

Developing polymer‐based nanocomposites with high thermal conductivity, mechanical performance, and electrical insulation becomes a huge challenge in both academia and industry. In this article, the synergistic effects of boron nitride (BN) nanosheets and carbon nanotubes (CNTs) on mechanical properties and thermal conductivity of epoxy nanocomposite adhesives were investigated. The results showed that the addition of one‐dimensional CNTs and two‐dimensional BN nanosheets into the epoxy matrix contributes to the formation of a three‐dimensional network and a larger contact surface between the nanofillers and the epoxy matrix. The hybrid filler of BN and CNTs provided significant improvements in thermal conductivity and mechanical properties of epoxy nanocomposite adhesives. At 1.06 vol% of BN‐CNTs, epoxy nanocomposite adhesives provide higher Young's modulus, fracture toughness (K1C), energy release rate (G1C), lap shear strength, and thermal stability compared with epoxy/BN nanocomposite adhesives. The thermal conductivity of epoxy/BN‐CNT nanocomposites recorded its maximum values of 0.49 K m−1 k−1 at 3.79 vol% and increased by 335% compared with 133% in case of epoxy/BN at the same fraction of 3.79 vol%.
Envelopes with microplastics generated from recycled plastic bags for crude oil sorption
Authors: Martins Larissa S. , Zanini Noelle C. , Botelho Alexandre L. S. , Mulinari Daniella R.
Published: May 2021

Oil spill accidents in marine environments and the lack of disposal of post‐consumer plastic are environmental problems worldwide. This study presents a sustainable alternative for both issues through envelopes filled with microplastics (MPs) from recycled bags for the sorption of spilled crude oil. Through particle size analysis by three different sieves (4, 9, and 20 mesh), different MP sizes were characterized by scanning electron microscope (SEM), Brunauer–Emmett–Teller (BET), density, contact angle (CA), and Fourier‐transform infrared spectroscopy (FTIR). According to their sizes, the MPs were distributed in envelopes and submitted to crude oil sorption capacity and efficiency evaluation. Three MP particle sizes were obtained (from the largest to the smallest, according to the sieve mesh, MP4, MP9, and MP20). SEM images of samples exhibited irregular and porous surfaces, and MP4 had the smallest pore size (8.6 μm). BET showed that MP4 had the highest surface area (0.074 m2/g). The CA > 90° exposed that all samples were hydrophobic. FTIR spectrum demonstrated that the samples from the recycled bags were made of high density polyethylene (HDPE). The MP4 envelopes also had the best crude oil sorption results in capacity and efficiency (1.73 g/g and 68%, respectively), being a promising recycled sorbent in crude oil spillage applications.
String (Gravi)photons, “Dark Brane Photons”, Holography and the Hypercharge Portal
Authors: Anastasopoulos P. , Bianchi M. , Consoli D. , Kiritsis E.
Published: May 2021

The mixing of graviphotons and dark brane photons to the Standard Model hypercharge is analyzed in full generality, in weakly‐coupled string theory. Both the direct mixing as well as effective terms that provide mixing after inclusion of SM corrections are estimated to lowest order. The results are compared with Effective Field Theory (EFT) couplings, originating in a hidden large‐N theory coupled to the SM where the dark photons are composite. The string theory mixing terms are typically subleading compared with the generic EFT couplings. The case where the hidden theory is a holographic theory is also analyzed, providing also suppressed mixing terms to the SM hypercharge.
Orientations of hexagonal chains with extremal values of the Randić index
Authors: Bermudo Sergio , Monsalve Juan , Rada Juan
Published: May 2021

Let D be a digraph with set of vertices V(D) and set of arcs A(D). Recently, the Randić index of D was extended to digraphs as
urn:x-wiley:00207608:media:qua26744:qua26744-math-0001
where and are the out‐degree and in‐degree of u and v, respectively. In this paper we study the extremal values of R over the set of all orientations of hexagonal chains with k hexagons.
Consensus‐based unscented Kalman filtering over sensor networks with communication protocols
Authors: Sheng Li , Huai Wuxiang , Niu Yichun , Gao Ming
Published: May 2021

This article is concerned with the consensus‐based distributed filtering problem for a class of general nonlinear systems over sensor networks with communication protocols. In order to avoid data collisions, the stochastic protocol and the Round‐Robin protocol are respectively introduced to schedule the data transmission between each node and its neighboring ones. A consensus‐based unscented Kalman filtering (UKF) algorithm is developed for the purpose of estimating the system states over sensor networks subject to communication protocols. Moreover, the exponential boundedness of estimation error in mean square is proved for the proposed algorithm. Finally, compared with the extended Kalman filtering, an experimental simulation example is provided to validate the effectiveness of the consensus‐based UKF algorithm.