bluuebunny/crossref_metadata_2025 huggingface dataset:
High SVR12 With 8-Week Course of Direct-Acting Antivirals in Adolescents and Children With Chronic Hepatitis C: A Comprehensive Analysis
Authors: Fu Zuqiang , Dong Chen , Ge Zhijun , Wang Chunhui , Zhang Yun , Shen Chao , Li Jun , Zhu Chuanlong , Wang Yan , Huang Peng , Yue Ming
Published: June 2021

Direct-acting antiviral (DAA) treatment for 8 weeks has a sustained virological response rate in adults with chronic hepatitis C. We have conducted a systematic review and meta-analysis to compare the efficacy and safety of the 8-week vs. 12/24-week DAA treatment in adolescents and children with CHC. The PubMed, Web of Science, and Cochrane databases were searched for the relevant articles from January 1, 2017 to August 28, 2020 and further screened for literature reviews on April 1, 2021. Pool proportions with 95% CIs for SVR12 were summarized with fixed/random effects models using Freeman–Tukey double arcsine transformation. Subgroup analysis was used to explore the source of heterogeneity. Thirty-six relevant publications were identified. For adolescents aged 12–17 years old, the pooled SVR12 and AE rate were 99.4% (95% CI: 98.7–99.9) and 34.7% (95% CI: 31.9–37.6). No one discontinued treatment due to drug intolerance. In addition, the SVR12 adolescents treated for 12 and 8/24 weeks were 99.3% (95% CI: 98.4–99.9) and 100%, respectively. The pooled SVR12 rate, AEs, and SAEs for children younger than 12 years were 98.9% (95% CI: 97.3–99.8), 51.6% (95% CI: 47.0–56.2), and 1.1% (95% CI: 0.4–2.5), respectively. The most common AE was fatigue (28.4%). The SVR12 was 98.8% (95% CI: 97.1–99.8) and 100% for the pediatric patients treated for 12 weeks and 8/24 weeks, respectively. Taken together, DAAs are generally effective against CHC and well-tolerated by the adolescents and children. A treatment duration of 8 weeks is equally effective and safe as 12/24 weeks in this demographic group.
Macular Vessel Density Changes in Young Adults With High Myopia: A Longitudinal Study
Authors: Shi Ya , Ye Luyao , Chen Qiuying , Hu Guangyi , Yin Yao , Fan Ying , Zhu Jianfeng , He Jiangnan , Zheng Zhi , Zou Haidong , Xu Xun
Published: June 2021

Background: To characterize the longitudinal changes of macular vessel density in young adults and its associated factors.

Methods: The right eyes of 309 participants (75 high myopic, 194 mild-to-moderate myopic, and 40 healthy) were followed up for 21 months. OCTA images were acquired at two visits using follow-up scans. Macular vessel density was calculated globally and in the nine early treatment diabetic retinopathy study (ETDRS) subfields of the macula superficial layer.

Results: The macular vessel density significantly decreased in young myopes after a 21-month follow up (p < 0.05), with variations among sectors. Compared with healthy eyes, HM group exhibited a faster reduction in global macular vessel density (p = 0.0307) as well as in sectors of inner-inferior (II), inner-temporal (IT), and outer-temporal (OT) (all p < 0.05). Multivariate regression analysis showed that longer baseline axial length (AL) was significantly associated with larger reduction of macular vessel density in the inner-inferior, inner-temporal and outer-temporal sectors (all p < 0.05).

Conclusions: Compared with emmetropes, high myopes presented greater loss of macular vessel density over time in global and in the inner-inferior, inner-temporal and outer-temporal sectors. A longer baseline AL was associated with larger changes of macular vessel density in the inner-inferior, inner-temporal and outer-temporal sectors.
Development of PET Radioligands Targeting COX-2 for Colorectal Cancer Staging, a Review of in vitro and Preclinical Imaging Studies
Authors: Dagallier Caroline , Avry François , Touchefeu Yann , Buron Frédéric , Routier Sylvain , Chérel Michel , Arlicot Nicolas
Published: June 2021

Colorectal cancer (CRC) is the second most common cause of cancer death, making early diagnosis a major public health challenge. The role of inflammation in tumorigenesis has been extensively explored, and among the identified markers of inflammation, cyclooxygenase-2 (COX-2) expression seems to be linked to lesions with a poor prognosis. Until now, COX-2 expression could only be accessed by invasive methods, mainly by biopsy. Imaging techniques such as functional Positron Emission Tomography (PET) could give access to in vivo COX-2 expression. This could make the staging of the disease more accurate and would be of particular interest in the exploration of the first metastatic stages. In this paper, we review recent progress in the development of COX-2 specific PET tracers by comparing the radioligands' characteristics and highlighting the obstacles that remain to be overcome in order to achieve the clinical development of such a radiotracer, and its evaluation in the management of CRC.
Serum Concentration of the Phytohormone Abscisic Acid Is Associated With Immune-Regulatory Mediators and Is a Potential Biomarker of Disease Severity in Chronic Obstructive Pulmonary Disease
Authors: Hoang Quynh Trang Mi , Nguyen Van Kinh , Oberacher Herbert , Fuchs Dietmar , Hernandez-Vargas Esteban A. , Borucki Katrin , Waldburg Nadine , Wippermann Jens , Schreiber Jens , Bruder Dunja , Veluswamy Priya
Published: June 2021

COPD and asthma are two distinct but sometimes overlapping diseases exhibiting varying degrees and types of inflammation on different stages of the disease. Although several biomarkers are defined to estimate the inflammatory endotype and stages in these diseases, there is still a need for new markers and potential therapeutic targets. We investigated the levels of a phytohormone, abscisic acid (ABA) and its receptor, LANCL2, in COPD patients and asthmatics. In addition, PPAR-γ that is activated by ABA in a ligand-binding domain-independent manner was also included in the study. In this study, we correlated ABA with COPD-propagating factors to define the possible role of ABA, in terms of immune regulation, inflammation, and disease stages. We collected blood from 101 COPD patients, 52 asthmatics, and 57 controls. Bronchoscopy was performed on five COPD patients and 29 controls. We employed (i) liquid chromatography–tandem mass spectrometry and HPLC to determine the ABA and indoleamine 2,3-dioxygenase levels, respectively; (ii) real-time PCR to quantify the gene expression of LANCL2 and PPAR-γ; (iii) Flow cytometry to quantify adipocytokines; and (iv) immunoturbidimetry and ELISA to measure CRP and cytokines, respectively. Finally, a multinomial regression model was used to predict the probability of using ABA as a biomarker. Blood ABA levels were significantly reduced in COPD patients and asthmatics compared to age- and gender-matched normal controls. However, PPAR-γ was elevated in COPD patients. Intriguingly, ABA was positively correlated with immune-regulatory factors and was negatively correlated with inflammatory markers, in COPD. Of note, ABA was increased in advanced COPD stages. We thereby conclude that ABA might be involved in regulation of COPD pathogenesis and might be regarded as a potential biomarker for COPD stages.
Maternal Deprivation in Rats Decreases the Expression of Interneuron Markers in the Neocortex and Hippocampus
Authors: Aksic Milan , Poleksic Joko , Aleksic Dubravka , Petronijevic Natasa , Radonjic Nevena V. , Jakovcevski Maja , Kapor Slobodan , Divac Nevena , Filipovic Branislav R. , Jakovcevski Igor
Published: June 2021

Early life stress has profound effects on the development of the central nervous system. We exposed 9-day-old rat pups to a 24 h maternal deprivation (MD) and sacrificed them as young adults (60-day-old), with the aim to study the effects of early stress on forebrain circuitry. We estimated numbers of various immunohistochemically defined interneuron subpopulations in several neocortical regions and in the hippocampus. MD rats showed reduced numbers of parvalbumin-expressing interneurons in the CA1 region of the hippocampus and in the prefrontal cortex, compared with controls. Numbers of reelin-expressing and calretinin-expressing interneurons were also reduced in the CA1 and CA3 hippocampal areas, but unaltered in the neocortex of MD rats. The number of calbinin-expressing interneurons in the neocortex was similar in the MD rats compared with controls. We analyzed cell death in 15-day-old rats after MD and found no difference compared to control rats. Thus, our results more likely reflect the downregulation of markers than the actual loss of interneurons. To investigate synaptic activity in the hippocampus we immunostained for glutamatergic and inhibitory vesicular transporters. The number of inhibitory synapses was decreased in the CA1 and CA3 regions of the hippocampus in MD rats, with the normal number of excitatory synapses. Our results indicate complex, cell type-specific, and region-specific alterations in the inhibitory circuitry induced by maternal deprivation. Such alterations may underlie symptoms of MD at the behavioral level and possibly contribute to mechanisms by which early life stress causes neuropsychiatric disorders, such as schizophrenia.
Dynamics of the Auditory Continuity Illusion
Authors: Cao Qianyi , Parks Noah , Goldwyn Joshua H.
Published: June 2021

Illusions give intriguing insights into perceptual and neural dynamics. In the auditory continuity illusion, two brief tones separated by a silent gap may be heard as one continuous tone if a noise burst with appropriate characteristics fills the gap. This illusion probes the conditions under which listeners link related sounds across time and maintain perceptual continuity in the face of sudden changes in sound mixtures. Conceptual explanations of this illusion have been proposed, but its neural basis is still being investigated. In this work we provide a dynamical systems framework, grounded in principles of neural dynamics, to explain the continuity illusion. We construct an idealized firing rate model of a neural population and analyze the conditions under which firing rate responses persist during the interruption between the two tones. First, we show that sustained inputs and hysteresis dynamics (a mismatch between tone levels needed to activate and inactivate the population) can produce continuous responses. Second, we show that transient inputs and bistable dynamics (coexistence of two stable firing rate levels) can also produce continuous responses. Finally, we combine these input types together to obtain neural dynamics consistent with two requirements for the continuity illusion as articulated in a well-known theory of auditory scene analysis: responses persist through the noise-filled gap if noise provides sufficient evidence that the tone continues and if there is no evidence of discontinuities between the tones and noise. By grounding these notions in a quantitative model that incorporates elements of neural circuits (recurrent excitation, and mutual inhibition, specifically), we identify plausible mechanisms for the continuity illusion. Our findings can help guide future studies of neural correlates of this illusion and inform development of more biophysically-based models of the auditory continuity illusion.
Radiological Configuration of the Vestibular Aqueduct Predicts Bilateral Progression in Meniere's Disease
Authors: Bächinger David , Schuknecht Bernhard , Dlugaiczyk Julia , Eckhard Andreas H.
Published: June 2021

Objective: Meniere's disease (MD) progresses from unilateral to bilateral disease in up to 50% of patients, often chronically and severely impairing balance and hearing functions. According to previous studies, 91% of bilateral MD patients demonstrate bilateral hypoplasia of the endolymphatic sac (ES) upon histological and radiological examination of their inner ears. Here, we seek to validate a radiological marker for ES hypoplasia that predicts the risk for future progression to bilateral MD in individual patients.

Methods: Patients with unilateral MD and radiological evidence for ES hypoplasia in either the clinically affected inner ear (cohort MDuni-hpuni) or both inner ears (cohort MDuni-hpbi) were included. Given our hypothesis that ES hypoplasia critically predisposes the inner ear to MD, we expected progression to bilateral MD only in the MDuni-hpbi cohort. To investigate eventual progression to bilateral MD, clinical, audiometric, and imaging data were retrospectively collected over follow-up periods of up to 31 years.

Results: A total of 44 patients were included in the MD-hpuni (n = 15) and MDuni-hpbi (n = 29) cohorts. In line with our radiology-based predictions, none (0/15) of the MD-hpuni patients exhibited progression to bilateral MD, whereas 20/29 (69%) MD-hpbi patients have already progressed to bilateral MD. Using the Kaplan–Meier estimator, bilateral disease progression would be observed in 100% of MD-hpbi patients 31 years after the initial diagnosis with an estimated median time to bilateral progression of 12 years. The nine MD-hpbi patients who, so far, remained with unilateral disease demonstrated a median time since initial (unilateral) MD diagnosis of only 6 years and are thus still expected to progress to bilateral disease.

Conclusion: Progression to bilateral MD adheres to predictions based on the radiological presence or absence of ES hypoplasia. This prognostic tool, if validated by prospective long-term studies, will provide clinically relevant information about a patient's future disease burden and will help to select more personalized treatment regimens.
Clinical Characteristics and Long-Term Prognosis of Anti-LGI1 Encephalitis: A Single-Center Cohort Study in Beijing, China
Authors: Li Tao-Ran , Zhang Yu-Di , Wang Qun , Shao Xiao-Qiu , Lyu Di-Yang , Lv Rui-Juan
Published: June 2021

Background: This study aimed to analyze the clinical characteristics of anti-leucine-rich glioma-inactivated protein 1 (LGI1) encephalitis patients and investigate prognostic factors by using a large-sample and long-term follow-up cohort.

Methods: The clinical data of 45 patients (29 males; mean age, 57.0 years) from May 2014 to August 2019 were collected. All patients were followed up by face-to-face interviews in the third month after discharge and then by telephone and/or face-to-face interviews every 6 months until November 2020. We evaluated each patient's response to the initial treatments at the first interview and divided them into “responders” and “nonresponders.” Relapses were recorded. At the end of follow-up, each patient was evaluated and reclassified into “complete recovery” or “unhealed” groups. Intergroup differences were assessed.

Results: All patients presented with seizures at the initial consultation. Other common manifestations included cognitive dysfunction (82.2%), psychiatric disturbance (66.7%), sleep disorder (54.5%), and hyponatremia (66.7%). During the follow-up period (32.8 ± 13.5 months), six patients experienced relapse within 6–37 months. We observed that the patients who did not respond to the initial treatments and those who relapsed all had a poor long-term prognosis. The patients in the “unhealed” group were older (p = 0.009), had a lower incidence of generalized tonic–clonic seizures (p = 0.041), and had a higher probability of cerebrospinal fluid (CSF) abnormalities (p = 0.024) than those in the “complete recovery” group.

Conclusion: Anti-LGI1 encephalitis was characterized by seizures, cognitive impairment, psychiatric disturbance, and sleep disorders and was often accompanied by hyponatremia. Patients who responded poorly to the initial treatments and those patients who relapsed had dismal long-term prognoses. Advanced age and CSF abnormalities may be risk factors for poor prognosis, but these still need to be verified.
Vestibular Function Measured Using the Video Head Impulse Test in Congenital Nystagmus and Vertigo: A Case Report
Authors: Denia-Lafuente Antonio , Lombardero Belén
Published: June 2021

In patients with congenital nystagmus (CN), the study of vestibular function is complicated by many factors related to the measurement of the vestibulo-ocular reflex (VOR) by means of caloric testing and the video head impulse test (vHIT), and to date no such studies have successfully employed the vHIT to evaluate vestibular function in these patients. We present a case with CN and vertigo in which peripheral vestibular function was evaluated using the vHIT system, including head impulse testing and the suppression head impulse protocol. We show that it is possible (a) to identify lateral VOR changes such as abnormalities resembling those produced by bilateral vestibular lesions, though not necessarily related to the same mechanism; (b) to identify peripheral VOR lesions of the vertical semicircular canals (SCC); and (c) to document compensation and recovery subsequent to these peripheral lesions during follow-up of patients with CN. vHIT is a useful tool that should be used to study vestibular function in patients with CN and vertigo, which could constitute a new clinical application of this technique.
Combination of Natural Compounds With Novel Non-thermal Technologies for Poultry Products: A Review
Authors: Barroug Soukaina , Chaple Sonal , Bourke Paula
Published: June 2021

Ensuring safe, fresh, and healthy food across the shelf life of a commodity is an ongoing challenge, with the driver to minimize chemical additives and their residues in the food processing chain. High-value fresh protein products such as poultry meat are very susceptible to spoilage due to oxidation and bacterial contamination. The combination of non-thermal processing interventions with nature-based alternatives is emerging as a useful tool for potential adoption for safe poultry meat products. Natural compounds are produced by living organisms that are extracted from nature and can be used as antioxidant, antimicrobial, and bioactive agents and are often employed for other existing purposes in food systems. Non-thermal technology interventions such as high-pressure processing, pulsed electric field, ultrasound, irradiation, and cold plasma technology are gaining increasing importance due to the advantages of retaining low temperatures, nutrition profiles, and short treatment times. The non-thermal unit process can act as an initial obstacle promoting the reduction of microflora, while natural compounds can provide an active obstacle either in addition to processing or during storage time to maintain quality and inhibit and control growth of residual contaminants. This review presents the application of natural compounds along with emerging non-thermal technologies to address risks in fresh poultry meat.
Cardia Gastric Cancer Is Associated With Increased PIK3CA Amplifications and HER2 Expression Than Noncardia Gastric Cancer According to Lauren Classification
Authors: Pai Shih-Min , Huang Kuo-Hung , Chen Ming-Huang , Fang Wen-Liang , Chao Yee , Lo Su-Shun , Li Anna Fen-Yau , Wu Chew-Wun , Shyr Yi-Ming
Published: June 2021

Background

To date, few reports have investigated genetic alterations and clinicopathological features in cardia and noncardia gastric cancer (GC).

Methods

In total, 435 GC patients receiving curative surgery were included. The clinicopathological features, recurrence patterns, prognoses and genetic alterations were compared between cardia and noncardia GC patients.

Results

Among the 435 enrolled patients, 47 (10.8%) had cardia GC. Compared with noncardia GC, cardia GC was associated with more intestinal-type tumors and similar initial recurrence patterns and 5-year overall survival (OS; 50.8% vs. 50.5%, P = 0.480) and disease-free survival (DFS; 48.6% vs. 48.9%, P = 0.392) rates. For both intestinal-type GC and diffuse-type GC, the clinicopathological features and 5-year OS and DFS rates were not significantly different between the cardia and noncardia GC patients. Multivariable analysis showed that cardia GC was not an independent prognostic factor. Compared with noncardia GC, cardia GC was associated with increased PIK3CA amplification than in patients with intestinal-type GC and was associated with increased HER2 expression in patients with diffuse-type GC.

Conclusions

Cardia GC is not an independent prognostic factor. In cardia GC patients with intestinal-type GC, PIK3CA amplification was more common, and in those with diffuse-type GC, HER2 expression was more common. Targeted therapy may be beneficial for these patient subgroups.
N6-Methyladenosine Modification of LncRNA DUXAP9 Promotes Renal Cancer Cells Proliferation and Motility by Activating the PI3K/AKT Signaling Pathway
Authors: Tan Lei , Tang Yiming , Li Hongbo , Li Pengju , Ye Yunlin , Cen Junjie , Gui Chengpeng , Luo Junhang , Cao Jiazheng , Wei Jinhuan
Published: June 2021

Most localized human renal clear cell carcinoma (ccRCC)-related deaths result from cancer recurrence and metastasis. However, the precise molecular mechanisms largely remain unknown. In recent years, an increasing number of long noncoding RNAs (lncRNAs) have been shown to be vital regulators of tumorigenesis. In this study, we characterized a lncRNA DUXAP9 and the upregulation of DUXAP9 was analyzed by quantitative real-time PCR in 112 pairs of localized ccRCC tumor tissues compared with adjacent normal tissues. Kaplan–Meier curves showed that patients of localized ccRCC with high DUXAP9 expression had poorer overall survival (P<0.01) and progression-free survival (P<0.05) than cases with low DUXAP9 expression. Multivariate Cox regression analysis also showed that high DUXAP9 expression was an independent risk factor for poor prognosis in localized ccRCC (p<0.05). DUXAP9 knockdown in renal cancer cells inhibited renal cancer cells proliferation and motility capacities in vitro and reversed epithelial–mesenchymal transition (EMT), whereas overexpression of DUXAP9 promoted renal cancer cells proliferation and motility capacities in vitro and induced EMT. Pull-down, RNA immunoprecipitation and RNA stability assays (involving actinomycin D) showed that DUXAP9 was methylated at N6-adenosine and binds to IGF2BP2, which increases its stability. DUXAP9 activate PI3K/AKT pathway and Snail expression in renal cancer cells. DUXAP9 may be useful as a prognostic marker and/or therapeutic target in localized ccRCC.
Development and Validation of Multicenter Predictive Nomograms for Locally Advanced Pancreatic Cancer After Chemoradiotherapy
Authors: Zhu Xiaofei , Liu Wenyu , Cao Yangsen , Su Tingshi , Zhu Xixu , Wang Yiyang , Ju Xiaoping , Zhao Xianzhi , Jiang Lingong , Ye Yusheng , Zhang Huojun
Published: June 2021

Objective

Due to common practice of hypofractionated radiotherapy in pancreatic cancer and heterogeneous chemotherapy regimens in previous studies, modified nomograms are required. Therefore, we aim to develop and validate prognostic nomograms for locally advanced pancreatic cancer (LAPC) after stereotactic body radiation therapy (SBRT) and chemotherapy.

Methods

The development cohort comprised 925 patients with LAPC receiving SBRT and gemcitabine-based chemotherapy in our center, while 297 patients from another two centers formed the validation cohort. Nomograms were created from COX models and internally validated by bootstrap. Model discriminations were evaluated by calibration plots and concordance index (C-index). A decision curve analysis (DCA) was performed to evaluate clinical benefits of nomograms. Additionally, recursive partitioning analysis (RPA) was used for stratifications of survival probability based on the total score of each patient calculated by nomograms.

Results

Weight loss, tumor diameter, radiation dose, CA19-9 kinetics after treatment and surgical resection were included in the nomogram for overall survival (OS), while the five factors plus performance status formed the nomogram for progression free survival (PFS). The corrected C-indexes for estimated 1-year and 2-year OS of the development cohort were 0.88 (95% CI: 0.85-0.91) and 0.86 (95% CI: 0.83-0.90). For those of the validation cohort, it was 0.88 (95% CI: 0.82-0.94) and 0.83 (95% CI: 0.74-0.91). Additionally, the corrected C-index for predicted 1-year PFS in the development and validation cohort was 0.83 (95% CI: 0.81-0.86) and 0.82 (95% CI: 0.78-0.87), respectively. The calibration plots showed good agreement of 1- and 2-year OS and 1-year PFS between the estimations and actual observations. Potential clinical benefits were demonstrated with DCA. Additionally, for 1- and 2-year OS and 1-year PFS, patients were stratified into four groups with different survival probability by RPA.

Conclusion

The validated nomograms provided useful predictions of OS and PFS for LAPC with chemoradiotherapy.
Effects of Ketoprofen and Morphine on Pain-Related Depression of Nestlet Shredding in Male and Female Mice
Authors: Garner Jamani B. , Marshall Laura S. , Boyer Nathaniel M. , Alapatt Vinaya , Miller Laurence L.
Published: June 2021

A primary goal in pain treatment is restoration of behaviors that are disrupted by pain. Measures of pain interference indicate the degree to which pain interferes with activities in pain patients, and these measures are used to evaluate the effects of analgesic drugs. As a result of the emphasis on the expression and treatment of functional impairment in clinical settings, preclinical pain researchers have attempted to develop procedures for evaluation of pain-related functional impairment in laboratory animals. The goal of the present study was to develop and validate a low cost procedure for the objective evaluation of pain-related depression of home cage behavior in mice. On test days, a 5 × 5 cm Nestlet was weighed prior to being suspended from the wire lid of the home cage of individually housed male and female ICR mice. Over the course of experimental sessions, mice removed pieces of the suspended Nestlet, and began to build a nest with the material they removed. Thus, the weight of the pieces of Nestlet that remained suspended at various time points in the session provided an indicator of the rate of this behavior. The results indicate that Nestlet shredding was stable with repeated testing, and shredding was depressed by intra-peritoneal injection of 0.32% lactic acid. The non-steroidal anti-inflammatory drug ketoprofen blocked 0.32% lactic acid-induced depression of shredding, but did not block depression of shredding by a pharmacological stimulus, the kappa opioid receptor agonist U69,593. The μ-opioid receptor agonist morphine did not block 0.32% lactic acid-induced depression of shredding when tested up to doses that depressed shredding in the absence of lactic acid. When noxious stimulus intensity was reduced by decreasing the lactic acid concentration to 0.18%, morphine was effective at blocking pain-related depression of behavior. In summary, the data from the present study support consideration of the Nestlet shredding procedure for use in studies examining mechanisms, expression, and treatment of pain-related functional impairment.
Recommendation for a Pilot MCDA Tool to Support the Value-Based Purchasing of Generic Medicines in the UAE
Authors: Farghaly Mohamed Naser , Al Dallal Sara Ahmad Mohammad , Fasseeh Ahmad Nader , Monsef Nahed AbdulKhaleq , Suliman Eldaw Abdalla Mohamed Ali , Tahoun Mohamed Attia , Abaza Sherif , Kaló Zoltán
Published: June 2021

Introduction:In recent periods the United Arab Emirates (UAE) has strengthened economic measures in its pharmaceutical policy by promoting local manufacturing and facilitating the use of generic medicines. International examples indicate the importance of quality control elements in the implementation of cost containment policies. Multicriteria Decision Analysis (MCDA) is increasingly used in health care to facilitate health care decision based on multiple objectives. Our objective was to develop a pilot MCDA tool for repeated use to support the value-based purchasing of generic medicines in the UAE.

Methods:An international evidence framework was adapted to UAE in a multistakeholder workshop organized by Dubai Health Authority. After validating the relevance of nine criteria in the local jurisdiction, participants decided the ranking and weight of each criterion by anonymous voting.

Results:The top four criteria focused on quality elements starting with real-world clinical or economic outcomes (with 19.8% weight), followed by the quality assurance of manufacturing (17.3%), then evidence on the equivalence with the original product (14.8%), and drug formulation and stability (12.3%). The pharmaceutical acquisition cost criteria ranked fifth with 9.4% weight. The bottom four criteria, including reliability of drug supply, macroeconomic benefit, pharmacovigilance and added value services related to the product had similar weights in the range of 5.5–7.7%.

Conclusion:Policy-makers in Dubai put high emphasis of value-based health care by incentivizing manufacturers of off-patent pharmaceuticals to generate additional scientific evidence compared to the mandatory minimum and acknowledging efforts to improve quality standards. The MCDA tool is considered suitable to improve the transparency and consistency of decision making in UAE for off-patent pharmaceuticals, and subsequently for other health technologies.
Molecular Insights Into the Gating Kinetics of the Cardiac hERG Channel, Illuminated by Structure and Molecular Dynamics
Authors: Zequn Zheng , Jiangfang Lian
Published: June 2021

The rapidly activating delayed rectifier K+ current generated by the cardiac hERG potassium channel encoded by KCNH2 is the most important reserve current for cardiac repolarization. The unique inward rectification characteristics of the hERG channel depend on the gating regulation, which involves crucial structural domains and key single amino acid residues in the full-length hERG channel. Identifying critical molecules involved in the regulation of gating kinetics for the hERG channel requires high-resolution structures and molecular dynamics simulation models. Based on the latest progress in hERG structure and molecular dynamics simulation research, summarizing the molecules involved in the changes in the channel state helps to elucidate the unique gating characteristics of the channel and the reason for its high affinity to cardiotoxic drugs. In this review, we aim to summarize the significant advances in understanding the voltage gating regulation of the hERG channel based on its structure obtained from cryo-electron microscopy and computer simulations, which reveal the critical roles of several specific structural domains and amino acid residues.
Long Noncoding RNAs: Novel Important Players in Adipocyte Lipid Metabolism and Derivative Diseases
Authors: Zhang Bin , Xu Saijun , Liu Jinyan , Xie Yong , Xiaobo Sun
Published: June 2021

Obesity, a global public health issue, is characterized by excessive adiposity and is strongly related to some chronic diseases including cardiovascular diseases and diabetes. Extra energy intake-induced adipogenesis involves various transcription factors and long noncoding RNAs (lncRNAs) that control lipogenic mRNA expression. Currently, lncRNAs draw much attention for their contribution to adipogenesis and adipose tissue function. Increasing evidence also manifests the pivotal role of lncRNAs in modulating white, brown, and beige adipose tissue development and affecting the progression of the diseases induced by adipose dysfunction. The aim of this review is to summarize the roles of lncRNAs in adipose tissue development and obesity-caused diseases to provide novel drug targets for the treatment of obesity and metabolic diseases.
Seed Priming With Protein Hydrolysates Improves Arabidopsis Growth and Stress Tolerance to Abiotic Stresses
Authors: Sorrentino Mirella , De Diego Nuria , Ugena Lydia , Spíchal Lukáš , Lucini Luigi , Miras-Moreno Begoña , Zhang Leilei , Rouphael Youssef , Colla Giuseppe , Panzarová Klára
Published: June 2021

The use of plant biostimulants contributes to more sustainable and environmentally friendly farming techniques and offers a sustainable alternative to mitigate the adverse effects of stress. Protein hydrolysate-based biostimulants have been described to promote plant growth and reduce the negative effect of abiotic stresses in different crops. However, limited information is available about their mechanism of action, how plants perceive their application, and which metabolic pathways are activating. Here we used a multi-trait high-throughput screening approach based on simple RGB imaging and combined with untargeted metabolomics to screen and unravel the mode of action/mechanism of protein hydrolysates in Arabidopsis plants grown in optimal and in salt-stress conditions (0, 75, or 150 mM NaCl). Eleven protein hydrolysates from different protein sources were used as priming agents in Arabidopsis seeds in three different concentrations (0.001, 0.01, or 0.1 μl ml–1). Growth and development-related traits as early seedling establishment, growth response under stress and photosynthetic performance of the plants were dynamically scored throughout and at the end of the growth period. To effectively classify the functional properties of the 11 products a Plant Biostimulant Characterization (PBC) index was used, which helped to characterize the activity of a protein hydrolysate based on its ability to promote plant growth and mitigate stress, and to categorize the products as plant growth promoters, growth inhibitors and/or stress alleviator. Out of 11 products, two were identified as highly effective growth regulators and stress alleviators because they showed a PBC index always above 0.51. Using the untargeted metabolomics approach, we showed that plants primed with these best performing biostimulants had reduced contents of stress-related molecules (such as flavonoids and terpenoids, and some degradation/conjugation compounds of phytohormones such as cytokinins, auxins, gibberellins, etc.), which alleviated the salt stress response-related growth inhibition.
COVID-19: A Political Virus? VOX’s Populist Discourse in Times of Crisis
Authors: Olivas Osuna José Javier , Rama José
Published: June 2021

Spain has been one of the hardest hit countries by the COVID-19 pandemic, and this crisis presented a window of opportunity for VOX, as it has for other far right parties, to raise its visibility as opposition force. This paper investigates whether the discourse of VOX has evolved during the pandemic and affected the political dynamics in Spain. This article proposes a new multidimensional strategy to measure the degree of populism in political communications, via quantitative and qualitative content analysis. It dissects the parliamentary speeches of the leader of VOX, Santiago Abascal, in the debates for the approval and extension of the “state of alarm” to fight against COVID-19 between March and June 2020. In order to assess the changes and relative intensity of populist features in Abascal’s parliamentary speeches we compared them with his speech during Pedro Sánchez’s investiture session as the Spanish President of the Government, in January 2020, and VOX’s latest political manifestos—2019 European and Spanish General Elections—, as well as with speeches of the representatives of the five main parties and coalitions during the COVID-19 debates in the Spanish Congress.Our paper shows that populists’ discourses are context-dependent and that their performances are not only shaped by crisis but also constitutive of crisis. The density of populist references in Abascal’s speeches grew steadily during the period analysed. Morality and antagonism overshadowed sovereignty and society as key populist attributes, and the tone of the discourse became increasingly hyperbolic. Moreover, Abascal’s discursive performances had a sort of contagion effect in other parties in the parliamentary sessions studied. People’s Party (Partido Popular–PP) leader Pablo Casado chose to follow VOX and harshly criticized the government, meanwhile the discourses of the speakers of Together We Can (Unidas Podemos–UP) and Catalan Republican Left (Esquerra Republicana de Catalunya–ERC), adopted a demonizing rhetoric against VOX and PP also grounded on a populist logic of articulation. This polarizing dynamic between competing Manichean discourses contributed to reinforce the sense of crisis by adding a political dimension to the already existing health and economic problems.
Perceived Discrimination and Motivation to Pursue Higher Education in Ethiopian-Origin Students: The Moderating Role of Ethnic Identity
Authors: Slobodin Ortal , Icekson Tamar , Herman Lee , Vaknin Ofri
Published: June 2021

Research has increasingly recognized the adverse effects of perceived discrimination on the academic outcomes of children and adolescents from ethnic and racial minority backgrounds. However, little is known about the association between perceived discrimination and the motivation of ethnic minority students to pursue higher education. Guided by an academic resilience framework, the current study examined the relationship between perceived discrimination and two types of motivation to pursue higher education (personal/career-driven and expectation-driven) among Ethiopian undergraduate students in Israel. In addition, we examined the role of ethnic identity as a potential moderator of this relationship. Participants were 183 undergraduate students of Ethiopian origin (77% females) who studied in 18 different higher-education institutes. Participants completed self-report questionnaires concerning their experiences of perceived discrimination, affiliation with their Ethiopian identity, and their reasons for pursuing higher education. Results showed that frequent discrimination experiences were positively related to a stronger ethnic identity and to higher levels of personal/career motivation to pursue higher education. Ethnic identity moderated the relationship between perceived discrimination and personal/career motivation so that the association was significant under low and moderate levels of ethnic identity but not under high levels. Our findings suggest that the awareness of discrimination may motivate students to pursue higher education and succeed in academia. However, the motivating force of perceived discrimination diminishes under high levels of ethnic identification. Further investigation is needed to explore how discrimination and ethnic identity work together to impact academic motivation in different developmental stages and socio-cultural contexts.
Hunters and Gatherers of Pictures: Why Photography Has Become a Human Universal
Authors: Kislinger Leopold , Kotrschal Kurt
Published: June 2021

Photography is ubiquitous worldwide. We analyzed why people take, share, and use personal photographs, independent of their specific cultural background. These behaviors are still poorly understood. Experimental research on them is scarce. Smartphone technology and social media have pushed the success of photography, but cannot explain it, as not all smartphone features are widely used just because they are available. We analyzed properties of human nature that have made taking and using photographs functional behaviors. We did this based on the four levels, which Nikolaas Tinbergen suggested for analyzing why animals behave in a particular way. Including findings from multiple disciplines, we developed a novel conceptual framework—the “Mental Utilization Hypothesis of Photography.” It suggests that people adopt photography because it matches with core human mental mechanisms mainly from the social domain, and people use photography as a cognitive, primarily social coping strategy. Our framework comprises a range of testable predictions, provides a new theoretical basis for future empirical investigations into photography, and has practical implications. We conclude that photography has become a human universal, which is based on context-sensitive mental predispositions and differentiates itself in the social and societal environment.
Impact of the Perceived Mental Stress During the COVID-19 Pandemic on Medical Students' Loneliness Feelings and Future Career Choice: A Preliminary Survey Study
Authors: Zheng Qiuyue , Lin Xianhao , He Lin , Freudenreich Thomas , Liu Tao
Published: June 2021

The outbreak of the COVID-19 epidemic continues to unfold globally, and its negative impact on the public's mental health is starting to reveal. Serving as reserve talents for the healthcare system, medical students are not yet professionally matured enough to face one of the worst global public health crises. This may exert increased mental stress and loneliness feelings, which in turn negatively influence medical students' future career choice. To address the issue, we conducted three online survey studies investigating how the epidemic affects the mental health as well as career attitude of medical students in China during the COVID-19 pandemic outbreak. The results revealed preliminary evidence showing that the perceived stress induced by the COVID-19 epidemic might negatively affect medical students' future career choice, and the feeling of loneliness may play a mediating role. This study invites more attention to medical students' mental health during severe public health crisis such as the COVID-19 pandemic.
Increased Risk of Death Triggered by Domestic Violence, Hunger, Suicide, Exhausted Health System during COVID-19 Pandemic: Why, How and Solutions
Authors: David Kenneth Bitrus , Aborode Abdullahi Tunde , Olaoye Damilola Quazeem , Enang Ndikpongkeabasi Victor , Oriyomi Aboaba Kazeem , Yunusa Ismaeel
Published: June 2021

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections, just like many other public health emergencies, is a well-established global health burden that has resulted in several changes in routines and lifestyles of people globally. The coronavirus disease (COVID-19) pandemic, caused by SARS-CoV-2, has directly or indirectly involved in the loss of lives of more than 3.24 million as of 6th May, 2021. The increasing threats posed by this pandemic were subsided by the swift and drastic measures put in place by different countries. As other causes of death before the emergence of COVID-19 still exist, the pandemic has further worsened their impact. The increased risks of COVID-19 deaths are not only due to the health burden it possesses, but also due to some other factors. These factors include domestic violence that becomes rampant, especially during lockdowns; hunger due to low economic development, unemployment, and loss of jobs; suicide due to depression; exhausted health system due to high level of COVID-19 cases and inability to contain it. As we move from the response phase into recovery, the pandemic’s direct and broader impacts on individuals, households, and communities will influence the capacity to recover. An understanding of these impacts is therefore required to develop priorities to support recovery. This paper identifies other causes of death amidst the pandemic, such as domestic violence, hunger, suicide, and exhausted health system, and how to minimize their effects.
How to Strengthen Wildlife Surveillance to Support Freedom From Disease: Example of ASF Surveillance in France, at the Border With an Infected Area
Authors: Desvaux Stéphanie , Urbaniak Christophe , Petit Thibaut , Chaigneau Pauline , Gerbier Guillaume , Decors Anouk , Reveillaud Edouard , Chollet Jean-Yves , Petit Geoffrey , Faure Eva , Rossi Sophie
Published: June 2021

Using a risk-based approach, the SAGIR network (dedicated to wildlife disease surveillance) had to strengthen surveillance activities after ASF was confirmed in Belgium in September 2018, very near the French border. Three new active dead wild boars search protocols supplemented opportunistic surveillance in Level III risk areas: patrols by volunteer hunters, professional systematic combing, and dog detection. Those protocols were targeted in terms of location and time and complemented each other. The main objectives of the designed surveillance system were (i) to assure early detection in case of introduction of the disease and (ii) to support the free status of the zone. Compiling the surveillance effort was thus a necessity to assure authorities and producer representatives that the sometimes low number of carcasses detected was not a consequence of no surveillance activities. The human involvement in implementing those activities was significant: more than 1000 8-h days just for the time spent in the field on active search activities. We calculated a specific indicator to enable a comparison of the surveillance results from different zones, including non-infected Belgian zones with strengthened surveillance activities. This was a first step in the evaluation of the efficacy of our surveillance activities in a WB population. Field experiments and modelling dead WB detection probability are planned to supplement this evaluation. Belgium regained its ASF-free status in November 2020, and ASF was not detected in France in either the WB or domestic pig populations.
Assessment of Novel Water Applied Prebiotic to Evaluate Gut Barrier Failure and Performance in Two Commercial Trials in Brazil. A Pilot Study With an Economic Perspective
Authors: Praxedes-Campagnoni Igor , Vecchi Bruno , Gumina Emanuel , Hernandez-Velasco Xochitl , Hall Jeffrey W. , Layton Sherry
Published: June 2021

The present study evaluated the effect of administration of a water applied prebiotic on gut barrier failure (Experiment 1) and performance in broiler chickens under commercial conditions (Experiment 2). Experiment 1, one thousand four hundred and forty day-of-hatch Ross broiler chickens were assigned to one of two experimental groups (n = 30 replicate pens/treatment; n = 24 chicks/pen). Birds in the treated group received the prebiotic orally in the drinking water (0.2ml/bird) on days 3 and 17 of age. The second group served as the untreated control group. On d 18, intestinal samples were analyzed by qRT-PCR to determine the expression of MUC2, IL-8, TGF-β4, and ZO-1. On d 17, d 28, and d 35 blood samples were collected to determine circulating endotoxin levels. On d 28, mucosal intestinal scrapping was collected to measure relative total sIgA levels. At d 42, liver samples were collected to evaluate liver bacterial translocation. In Experiment 2, the prebiotic was evaluated in two commercial trials. Chickens were raised under normal production conditions and fed a 3-phase commercial basal diet with enramycin (7 g/ton). In Trial 1, 8,974,237 broiler chickens were treated with the prebiotic. The prebiotic was administered in the drinking water (0.2 mL/bird) following the manufacture label instructions at day three and seventeen of life. Production parameters were compared to historical information from the company over the same broiler operation and production cycles. For trial 2, 921,411 broiler chickens were treated with the prebiotic as in Trial 1. In Experiment 1, treated chickens showed a significant (P < 0.05) increase in mRNA expression of MUC2, TGF-β4, IL-8, ZO-1, and sIgA, but a significant reduction of serum endotoxin levels and incidence of liver lactose positive bacterial translocation when compared to non-treated chickens. In both trials of Experiment 2, a significant reduction in total mortality was observed in the treated chickens when compared with the historical farm data. Economic analysis utilizing the total percent of mortality revealed a $1: $2.50 USD and $1: $4.17 USD return for Trial 1 and Trial 2, respectively. The results suggest that the prebiotic positively influences gastrointestinal integrity and performance.