bluuebunny/crossref_metadata_2025 huggingface dataset:
A VOSviewer-Based Bibliometric Analysis of Prescription Refills
Authors: Fu Runchen , Xu Haiping , Lai Yongjie , Sun Xinying , Zhu Zhu , Zang Hengchang , Wu Yibo
Published: June 2022

Purpose

Prescription refills are long-term prescriptions for chronic patients in stable status, which varies from country to country. A well-established prescription refill system is beneficial for chronic patients’ medication management and facilitates the efficacy of clinical care. Therefore, we carried out a bibliometric analysis to examine the development of this field.

Publications on prescription refills from 1970 to 2021 were collected in the Web of Science Core Collection (WoSCC). Search strategy TS = “prescri* refill*” OR “medi* refill*” OR “repeat prescri*” OR “repeat dispens*” OR TI = refill* was used for search. VOSviewer was applied to visualize the bibliometric analysis. A total of 319 publications were found in WoSCC. Study attention on prescription refills has shown a steady rise but is still low in recent years. The United States was the most productive country, which had the highest total citations, average citations per publication, and the highest H-index, and participated in international collaboration most frequently. The University of California system was the most productive institution. The U.S. Department of Veterans Affairs was the institution with the most citations, most average citation, and highest H-index. Sundell was the most productive author, and Steiner J. F. was the most influential author. “Adherence,” “medication,” and “therapy” were the most prominent keywords.

Conclusion

Publications on prescription refills have increased rapidly and continue to grow. The United States had the leading position in the area. It is recommended to pay closer attention to the latest hotspots, such as “Opioids,” “Surgery,” “Differentiated care,” and “HIV.”
SLC12A3 Variation and Renal Function in Chinese Patients With Hypertension
Authors: Huang Chin-Chou , Chung Chia-Min , Yang Chih-Yu , Leu Hsin-Bang , Huang Po-Hsun , Lin Liang-Yu , Wu Tao-Cheng , Lin Shing-Jong , Pan Wen-Harn , Chen Jaw-Wen
Published: June 2022

Objective

SLC12A3 (solute carrier family 12 member 3) gene variants are associated with diabetic nephropathy; however, their association with hypertensive nephropathy remains unknown. We aimed to investigate the association between SLC12A3 gene polymorphisms and renal function in patients with hypertension.

Methods

Participants from three non-diabetic hypertensive cohorts, including young-onset hypertension (cohort 1, n = 882), treatment-naïve hypertension (cohort 2, n = 90), and follow-up cohort (cohort 3, n = 166), underwent genotyping for single nucleotide polymorphisms in SLC12A3. Renal events were defined as a >25 and >50% decline in estimated glomerular filtration rate (eGFR).

Results

In cohort 1, SLC12A3 rs16963397 C/C or C/G (P = 0.005), rs13334864 C/C or C/T (P = 0.020), and rs7187932 A/A or A/G polymorphisms (P = 0.014) had higher eGFRs compared to their counterparts, with similar findings observed in cohort 2. In cohort 3, over a mean follow-up of 5.8 ± 1.7 years, participants with either SLC12A3 rs16963397 C/C or rs13334864 C/C polymorphisms had more >25 and >50% eGFR decline than their counterparts (log-rank test, P = 0.058 and P = 0.038, respectively). Cox regression analysis revealed that SLC12A3 rs16963397 C/C and rs13334864 C/C polymorphisms were significantly associated with an increased risk of >25% [hazard ratio (HR), 3.294; 95% confidence interval (CI), 1.158–9.368; P = 0.025] and >50% decline in eGFR (HR, 18.630; 95% CI, 1.529–227.005, P = 0.022) than their counterparts.

Conclusion

SLC12A3 polymorphisms are associated with renal function in Chinese patients with hypertension.
Severity and Outcomes of Dengue in Hospitalized Jamaican Children in 2018–2019 During an Epidemic Surge in the Americas
Authors: Lue Aileen May , Richards-Dawson Michelle-Ann Elizabeth Hue , Gordon-Strachan Georgiana Marie , Kodilinye Syed Matthew , Dunkley-Thompson Jacqueline Anne Theresa , James-Powell Tracia Dahlia , Pryce Curtis Alphonso , Mears Chadwic De'sean , Anzinger Joshua James , Webster-Kerr Karen , Christie Celia Dana Claire
Published: June 2022

Objective

In 2019, dengue was among the “top-ten threats to global health,” with 3.1 million cases reported from the Americas, the highest ever. Simultaneously, Jamaica reported its largest dengue outbreak in 40 years, following Chikungunya and Zika virus epidemics, in 2014 and 2016–2017, respectively. We describe dengue in children admitted to five hospitals in Jamaica during August 2018 through September 2019.

Methods

Hospitalized children and adolescents aged 0 to 15 years with dengue were managed using PAHO/WHO criteria. Data were extracted from questionnaires, entered into a dataset on Microsoft Excel version 2016, exported to SPSS version 20 and analyzed. Groups were compared using Student's t-test for normally distributed parametric data. Chi-square analysis, or Fisher's exact test was used for categorical variables. A p-value < 0.05 was considered statistically significant.

Results

There were 339 children, 245 (72.3%) aged 1–10 years, males:females 1:1. Classification was “dengue without warning signs” 53 (15.3%), “dengue with warning signs” 218 (64.3%) and “severe dengue” 68 (20%). Co-morbidities were reported in 88 (26%). Hemoglobin SC disease was associated with severe dengue with hemorrhage (p = 0.005). Organ-system involvement occurred in 334 (98.5%) including gastrointestinal 317 (93.5%), hematologic 311 (91.7%) and musculoskeletal 180 (53.1%). Thirty-nine (11.5%) had 5–7 organ-systems involved. Metabolomics emphasized increased hepatic transaminases 245 (72.3%), lactate dehydrogenase 164 (48.4%) and creatine phosphokinase 84 (24.8%) approaching the high thousands (121,560 u/L), both were markers for severe disease (p < 0.002). Thirteen (3.8%) received intensive care. Dengue was laboratory-confirmed in 220 (78.9%): NS1 antigen-positive (218); RT-PCR-positive (23), with an overlap of NS1 antigen and RT-PCR positive (21); DENV-3 serotype (20). Seventeen (5%) died, 16 (94.1%) had severe dengue and 11 (64.7%) succumbed within 24 to 48 h of admission despite resuscitation and transfusion of blood products.

Conclusion

Severe dengue with increased attributable mortality occurred in hospitalized children after Jamaica's maiden Zika epidemic.
A Pilot Study of Using Smartphone Application vs. Routine Follow-Up for Patient Care in Advanced Non-Small Cell Lung Cancer During the COVID-19 Pandemic Era
Authors: Prasongsook Naiyarat , Seetalarom Kasan , Saichaemchan Siriwimon , Udomdamrongkul Kittipong
Published: June 2022

Introduction

Cancer care monitoring should be adapted regarding COVID-19 pandemic preparedness plans. Lung Cancer Care application was a mobile application program to monitor adverse events and report outcomes. This study is aimed to invent a new mobile application evaluating patient-reported outcome (PRO) for patients with non-small cell lung cancer (NSCLC) and to evaluate the validity of a mobile application, particularly during the COVID-19 pandemic era.

Methods

The validity of the application was tested, and Functional Assessment of Cancer Therapy-Lung (FACT-L) questionnaires were contained in the mobile application-based PRO. Patients were randomly assigned to use mobile application-based PRO vs. routine follow-up. The primary end point was to compare the quality of life (QoL) scores between two groups. A secondary end point was overall survival (OS) and the outcomes of progressive disease (PD) between the two groups.

Results

In total, 33 patients with advanced NSCLC were enrolled. Patients in the mobile application group had higher FACT-L scores at 3 months than patients with a routine follow-up arm (106 ± 5.97 vs. 99.96 ± 5.74, p-value = 0.07). The median follow-up time was 5.43 months; patients with mobile application had an insignificant increase in median OS when compared with patients using routine follow-up (4.53 vs. 2.93 months, p-value = 0.85). The sensitivity, specificity, positive predictive value (PPV), and negative predictive (NPV) value of this application for predicting disease progression were 50, 83.3, 66.7, and 70%, respectively.

Conclusion

Self-reported symptoms by Lung Cancer Care application improved QoL and were similar in monitoring outcomes to face-to-face follow-up. This tool is applicable for patients with cancer to make monitoring as safe as possible for physical distancing during the COVID-19 pandemic era.
The Differential Responses of Coastal Diatoms to Ocean Acidification and Warming: A Comparison Between Thalassiosira sp. and Nitzschia closterium f.minutissima
Authors: Cai Ting , Feng Yuanyuan , Wang Yanan , Li Tongtong , Wang Jiancai , Li Wei , Zhou Weihua
Published: June 2022

Marine diatoms are one of the marine phytoplankton functional groups, with high species diversity, playing important roles in the marine food web and carbon sequestration. In order to evaluate the species-specific responses of coastal diatoms to the combined effects of future ocean acidification (OA) and warming on the coastal diatoms, we conducted a semi-continuous incubation on the large centric diatom Thalassiosira sp. (~30 μm) and small pennate diatom Nitzschia closterium f.minutissima (~15 μm). A full factorial combination of two temperature levels (15 and 20°C) and pCO2 (400 and 1,000 ppm) was examined. The results suggest that changes in temperature played a more important role in regulating the physiology of Thalassiosira sp. and N. closterium f.minutissima than CO2. For Thalassiosira sp., elevated temperature significantly reduced the cellular particulate organic carbon (POC), particulate organic nitrogen (PON), particulate organic phosphate (POP), biogenic silica (BSi), chlorophyll a (Chl a), and protein contents, and the C:N ratio. CO2 only had significant effects on the growth rate and the protein content. However, for the smaller pennate diatom N. closterium f.minutissima, the growth rate, POC production rate, and the C:P ratio significantly increased with an elevated temperature, whereas the cellular POP and BSi contents significantly decreased. CO2 had significant effects on the POC production rate, cellular BSi, POC, and PON contents, the C:P, Si:C, N:P, and Si:P ratios, and sinking rate. The interaction between OA and warming showed mostly antagonistic effects on the physiology of both species. Overall, by comparison between the two species, CO2 played a more significant role in regulating the growth rate and sinking rate of the large centric diatom Thalassiosira sp., whereas had more significant effects on the elemental compositions of the smaller pennate diatom N. closterium f.minutissima. These results suggest differential sensitivities of different diatom species with different sizes and morphology to the changes in CO2/temperature regimes and their interactions.
New Mutations in cls Lead to Daptomycin Resistance in a Clinical Vancomycin- and Daptomycin-Resistant Enterococcus faecium Strain
Authors: Li Weiwei , Hu Jiamin , Li Ling , Zhang Mengge , Cui Qingyu , Ma Yanan , Su Hainan , Zhang Xuhua , Xu Hai , Wang Mingyu
Published: June 2022

Daptomycin (DAP), a last-resort antibiotic for treating Gram-positive bacterial infection, has been widely used in the treatment of vancomycin-resistant enterococci (VRE). Resistance to both daptomycin and vancomycin leads to difficulties in controlling infections of enterococci. A clinical multidrug-resistant Enterococcus faecium EF332 strain that shows resistance to both daptomycin and vancomycin was identified, for which resistance mechanisms were investigated in this work. Whole-genome sequencing and comparative genomic analysis were performed by third-generation PacBio sequencing, showing that E. faecium EF332 contains four plasmids, including a new multidrug-resistant pEF332-2 plasmid. Two vancomycin resistance-conferring gene clusters vanA and vanM were found on this plasmid, making it the second reported vancomycin-resistant plasmid containing both clusters. New mutations in chromosomal genes cls and gdpD that, respectively, encode cardiolipin synthase and glycerophosphoryl diester phosphodiesterase were identified. Their potential roles in leading to daptomycin resistance were further investigated. Through molecular cloning and phenotypic screening, two-dimensional thin-layer chromatography, fluorescence surface charge test, and analysis of cardiolipin distribution patterns, we found that mutations in cls decrease surface negative charges of the cell membrane (CM) and led to redistribution of lipids of CM. Both events contribute to the DAP resistance of E. faecium EF332. Mutation in gdpD leads to changes in CM phospholipid compositions, but cannot confer DAP resistance. Neither mutation could result in changes in cellular septa. Therefore, we conclude that the daptomycin resistance of E. faecium EF332 is conferred by new cls mutations. This work reports the genetic basis for vancomycin and daptomycin resistance of a multidrug-resistant E. faecium strain, with the finding of new mutations of cls that leads to daptomycin resistance.
Comparative Transcriptome Analysis Provides Insights Into the Mechanism by Which 2,4-Dichlorophenoxyacetic Acid Improves Thermotolerance in Lentinula edodes
Authors: Xu Ruiping , Zhou Shasha , Song Jiaxin , Zhong Haiying , Zhu Tianwen , Gong Yuhua , Zhou Yan , Bian Yinbing
Published: June 2022

As the widest cultivated edible mushroom worldwide,Lentinula edodessuffers serious yield and quality losses from heat stress during growth and development, and in our previous study, exogenous 2,4-Dichlorophenoxyacetic acid (2,4-D) was found to improve the thermotolerance ofL. edodesstrain YS3357, but the molecular mechanism remains unclear. Here, we explored the potential protective mechanism of exogenous 2,4-D against heat stress by transcriptome analysis. 2,4-D possible improve the thermotolerance ofL. edodesthrough regulating antioxidant genes, transcription factors, energy-provision system, membrane fluidity, and cell wall remodeling. Furthermore, 2,4-D was also found to regulate the saturation levels of fatty acids and ATP content inL. edodesmycelium under heat stress. This study proposed a regulatory network of 2,4-D in regulatingL. edodesresponse to heat stress, providing a theoretical basis for improvingL. edodesthermotolerance, and facilitating the understanding of the molecular mechanism of exogenous hormones in alleviating abiotic stress damage to macrofungi.
Health-Related Predictors of Changes in Cognitive Status in Community-Dwelling Older Individuals
Authors: Trevisan Caterina , Siviero Paola , Limongi Federica , Noale Marianna , Maggi Stefania
Published: June 2022

Given the rising numbers of older people living with dementia, this study focuses on identifying modifiable health-related factors associated with changes in cognitive status. The predictors of 1-year conversion from Preserved Cognitive Health (PCH) and Mild Cognitive Impairment (MCI) in older adults were evaluated. Two logistic regression models were performed on data from an Italian multicenter population-based study; both included sociodemographic factors, family history of dementia (FHD), risk behaviors, and depressive symptoms. The first model considered also disease clusters, while the second one included diseases' number and biochemical parameters. The sample involved 459 participants (61.4% women, median age 75 years). Of the 80 PCH individuals at baseline, after 1 year 35 (43.8%) were stable, 44 (55.0%) progressed to MCI, none to dementia, and one to unclassified status. Of the 379 MCI participants at baseline, after 1 year 281 (74.1%) remained stable, 38 (10.0%) reverted to PCH, 15 (4.0%) progressed to dementia, and 45 (11.9%) become unclassifiable. Hypertension/bone and joint diseases cluster was the only predictor of PCH progression to MCI; age and depression were associated with MCI progression to dementia; FHD was associated with MCI reversion to PCH. More diseases and fewer white blood cells were associated with MCI progression to dementia; more diseases and lower platelets were associated with the transition from MCI to unclassifiable; higher Na and lower TSH levels were associated with MCI reversion. The treatment or management of some chronic conditions and electrolyte imbalances may help attenuate cognitive deterioration in older adults with no or MCI.
Promises and Pitfalls of NMDA Receptor Antagonists in Treating Violent Aggression
Authors: Bartsch Caitlyn J. , Nordman Jacob C.
Published: June 2022

Treatment options for chronically aggressive individuals remain limited despite recent medical advances. Traditional pharmacological agents used to treat aggression, such as atypical antipsychotics, have limited efficacy and are often replete with dangerous side effects. The non-competitive NMDAR antagonists ketamine and memantine are promising alternatives, but their effects appear to be highly dependent on dosage, context, and personal experience. Importantly, these drugs can increase aggression when combined with substances of abuse or during periods of heightened stress. This is likely due to mechanistic differences operating at specific synapses under different contexts. Previous findings from our lab and others have shown that early life stress, substance abuse, and attack experience promote aggression through NMDAR-dependent synaptic plasticity within aggression-related brain circuits. Ketamine and memantine affect these types of aggression in opposite ways. This has led us to propose that ketamine and memantine oppositely affect aggression brought on by early life stress, substance abuse, or attack experience through opposite effects on NMDAR-dependent synaptic plasticity. This would account for the persistent effects of these drugs on aggression and suggest they could be leveraged as a more long-lasting treatment option. However, a more thorough examination of the effects of ketamine and memantine on cellular and synaptic function will be necessary for responsible administration. Additionally, because the effects of ketamine and memantine are highly dependent on prior drug use, traumatic stress, or a history of aggressive behavior, we propose a more thorough medical evaluation and psychiatric assessment will be necessary to avoid possible adverse interactions with these drugs.
Aspirin for Primary Stroke Prevention; Evidence for a Differential Effect in Men and Women
Authors: Gdovinova Zuzana , Kremer Christine , Lorenzano Svetlana , Dawson Jesse , Lal Avtar , Caso Valeria
Published: June 2022

Background:

The use of aspirin for primary prevention of cardiovascular events in men and women remains controversial. Our study aimed to investigate the role of aspirin in primary stroke prevention in men and women and the effect of aspirin on risk of ischemic stroke in patients with covert cerebral small vessel disease (ccSVD).

Methods

We performed systematic searches of the PubMed, and Cochrane Library databases, covering the period from the inception of each database to May 2021. The incidence of any ischemic stroke (IS) or hemorrhagic stroke (HS) was the main outcome. The incidence of stroke overall, both ischemic (IS) and hemorrhagic (HS), was the main outcome.

Results

From 531 abstracts, 11 randomized control trials which assessed primary prevention of cardiovascular events in men and women were included. Only one study assessed the risk of aspirin in people with ccSVD. In women, there was significant decrease in the risk of stroke (OR 0.85 [95% CI 0.73, 0.99], p = 0.03) and IS (OR 0.76 [0.63, 0.93], p = 0.008) with aspirin compared to placebo while no increase in the risk of HS was found (OR 1.78 [0.61, 5.19], p = 0.29). In men, aspirin did not affect the risk of stroke (OR 1.13 [0.97, 1.31], p = 0.12) and IS (OR 0.94 [0.67, 1.32], p = 0.72) but increased the risk of HS with borderline statistical significance (OR 1.99 [0.99, 4.03], p = 0.05) compared to placebo. Aspirin significantly increased major bleedings in both sexes (p < 0.05). We found no evidence to support the use of aspirin in patients with ccSVD.

Conclusion

Our meta-analysis suggests aspirin is effective in primary prevention of stroke and IS in women with no clear increased risk of HS. However, it was associated with an overall increased risk of bleeding. Aspirin is not recommended in ccSVD.
Immunoglobulin G4-Related Spinal Intramedullary Inflammatory Pseudotumor: A Case Report and Literature Review
Authors: Qi Zhou , Liu Jianli , Li Guoqiang , Zhang Yinian
Published: June 2022

Immunoglobulin G4-related disease (IgG4-RD) is an autoimmune disease that affects several organs. An inflammatory pseudotumor is a histologically proven benign tumor-like lesion that most commonly involves the lung and orbit. It is rare in the central nervous system, but rarest in the spinal canal. In this report, we present a case of IgG4-related intramedullary spinal inflammatory pseudotumor, along with a literature review. A 29-year-old male was transferred to the Department of Neurosurgery of Lanzhou University Second Hospital with progressive quadriparesis after numbness and weakness in both lower limbs for 50 days. Enhanced magnetic resonance imaging (MRI) of the spine revealed an isointense signal on T1-weighted images and a hyperintense signal on T2-weighted images from an enhanced mass located at the thoracic vertebrae region, for which a schwannoma was highly suspected. Then, a posterior median approach was adopted. The lesion was resected. The patient received further glucocorticoid after the diagnosis of an IgG4-related inflammatory pseudotumor was established, and the patient's symptoms improved, such as quadriparesis and lower limb weakness. This case highlights the importance of considering IgG4-related inflammatory pseudotumor as a differential diagnosis in patients with lesions involving the spinal intramedullary compartment and lower limb weakness when other more threatening causes have been excluded. IgG4-related inflammatory pseudotumor is etiologically unclear and prognostically unpredictable, and imaging may not help establish the diagnosis of IgG4-related inflammatory pseudotumor due to its resemblance to malignant tumors, and total resection might not be warranted. Glucocorticoid and surgery are usually the first-line treatments used.
40 Hz Blue LED Relieves the Gamma Oscillations Changes Caused by Traumatic Brain Injury in Rat
Authors: Yang Xiaoyu , Li Xuepei , Yuan Yikai , Sun Tong , Yang Jingguo , Deng Bo , Yu Hang , Gao Anliang , Guan Junwen
Published: June 2022

Background

Photobiomodulation (PBM) using low-level light-emitting diodes (LEDs) can be rapidly applied to various neurological disorders safely and non-invasively.

Materials and Methods

Forty-eight rats were involved in this study. The traumatic brain injury (TBI) model of rat was set up by a controlled cortical impact (CCI) injury. An 8-channel cortex electrode EEG was fixed to two hemispheres, and gamma oscillations were extracted according to each electrode. A 40 hz blue LED stimulation was set at four points of the frontal and parietal regions for 60 s each, six times per day for 1 week. Modified Neurologic Severity Scores (mNSS) were used to evaluate the level of neurological function.

Results

In the right-side TBI model, the gamma oscillation decreased in electrodes Fp2, T4, C4, and O2; but significantly increased after 1 week of 40 hz Blue LED intervention. In the left-side TBI model, the gamma oscillation decreased in electrodes Fp1, T3, C3, and O1; and similarly increased after 1 week of 40 hz Blue LED intervention. Both left and right side TBI rats performed significantly better in mNSS after 40 hz Blue LED intervention.

Conclusion

TBI causes the decrease of gamma oscillations on the injured side of the brain of rats. The 40 hz Blue LED therapy could relieve the gamma oscillation changes caused by TBI and improve the prognosis of TBI.
Neural Mechanisms Underlying the Effects of Novel Sounds on Task Performance in Children With and Without ADHD
Authors: Tegelbeckers Jana , Brechmann André , Breitling-Ziegler Carolin , Bonath Bjoern , Flechtner Hans-Henning , Krauel Kerstin
Published: June 2022

Distractibility is one of the key features of attention deficit hyperactivity disorder (ADHD) and has been associated with alterations in the neural orienting and alerting networks. Task-irrelevant stimuli are thus expected to have detrimental effects on the performance of patients with ADHD. However, task-irrelevant presentation of novel sounds seems to have the opposite effect and improve subsequent attentional performance particularly in patients with ADHD. Here, we aimed to understand the neural modulations of the attention networks underlying these improvements. Fifty boys (25 with ADHD) participated in a functional magnetic resonance imaging (fMRI) study in which unique (novel) or repeatedly presented (familiar) sounds were placed before a visual flanker task in 2/3 of the trials. We found that presenting any sound improved task performance in all participants, but the underlying neural mechanisms differed for the type of sound. Familiar sounds led to a stronger increase in activity in the left posterior insula in patients with ADHD compared to typically developing peers. Novel sounds led to activations of the fronto-temporoparietal ventral attention network, likewise in ADHD and TD. These changes in signaling by novelty in the right inferior frontal gyrus were directly related to improved response speed showing that neural orienting network activity following novel sounds facilitated subsequent attentional performance. This mechanism of behavioral enhancement by short distractions could potentially be useful for cognitive trainings or homework situations.
Brain Mapping of Behavioral Domains Using Multi-Scale Networks and Canonical Correlation Analysis
Authors: Fernandez-Iriondo Izaro , Jimenez-Marin Antonio , Sierra Basilio , Aginako Naiara , Bonifazi Paolo , Cortes Jesus M.
Published: June 2022

Simultaneous mapping of multiple behavioral domains into brain networks remains a major challenge. Here, we shed some light on this problem by employing a combination of machine learning, structural and functional brain networks at different spatial resolutions (also known as scales), together with performance scores across multiple neurobehavioral domains, including sensation, motor skills, and cognition. Provided by the Human Connectome Project, we make use of three cohorts: 640 participants for model training, 160 subjects for validation, and 200 subjects for model performance testing thus enhancing prediction generalization. Our modeling consists of two main stages, namely dimensionality reduction in brain network features at multiple scales, followed by canonical correlation analysis, which determines an optimal linear combination of connectivity features to predict multiple behavioral performance scores. To assess the differences in the predictive power of each modality, we separately applied three different strategies: structural unimodal, functional unimodal, and multimodal, that is, structural in combination with functional features of the brain network. Our results show that the multimodal association outperforms any of the unimodal analyses. Then, to answer which human brain structures were most involved in predicting multiple behavioral scores, we simulated different synthetic scenarios in which in each case we completely deleted a brain structure or a complete resting state network, and recalculated performance in its absence. In deletions, we found critical structures to affect performance when predicting single behavioral domains, but this occurred in a lesser manner for prediction of multi-domain behavior. Overall, our results confirm that although there are synergistic contributions between brain structure and function that enhance behavioral prediction, brain networks may also be mutually redundant in predicting multidomain behavior, such that even after deletion of a structure, the connectivity of the others can compensate for its lack in predicting behavior.
Evaluation of Antioxidative and Neuroprotective Activities of Total Flavonoids From Sea Buckthorn (Hippophae rhamnoides L.)
Authors: Wang Zheng , Wang Wenqian , Zhu Changlong , Gao Xiangdong , Chu Weihua
Published: June 2022

The aim of this study was to investigate the antioxidative and neuroprotective activities of total flavonoids from sea buckthorn (Hippophae rhamnoides L.) (TFH). Results indicated that TFH possessed DPPH radicals, hydroxyl radicals and superoxide anions scavenging activities. The neuroprotective potential was assessed with acetylcholinesterase (AChE) and monoamine oxidase A (MAO-A). The inhibition rates of AChE and MAO-A by 50 μg/ml TFH were 75.85 and 51.22%, respectively. The in vivo antioxidative and neuroprotective potential of TFH were explored in Caenorhabditis elegans. In the longevity assay, TFH (50 μg/ml) significantly increased the lifespan of wild-type C. elegans (29.40%). In the hydrogen peroxide-induced oxidative stress challenge, the antioxidant capacity of TFH-treated wild-type C. elegans was significantly enhanced. The C. elegans mutant strain CL4176 was used to study the neuroprotective effect of TFH in vivo. Results showed that TFH significantly delayed paralysis in C. elegans CL4176. Our study suggested total flavonoids from sea buckthorn (Hippophae rhamnoides L.) had the potential as an antioxidative and neuroprotective agent to extend aging and treat neurodegenerative diseases.
Effects of a Single Dose of a Creatine-Based Multi-Ingredient Pre-workout Supplement Compared to Creatine Alone on Performance Fatigability After Resistance Exercise: A Double-Blind Crossover Design Study
Authors: Negro Massimo , Cerullo Giuseppe , Perna Simone , Beretta-Piccoli Matteo , Rondanelli Mariangela , Liguori Giorgio , Cena Hellas , Phillips Stuart M. , Cescon Corrado , D’Antona Giuseppe
Published: June 2022

Background

This study aims to investigate the acute effects of a single oral administration of a creatine-based multi-ingredient pre-workout supplement (MIPS) on performance fatigability and maximal force production after a resistance exercise protocol (REP).

Methods

Eighteen adult males (age: 23 ± 1 years; body mass: 76.4 ± 1.5 kg; height: 1.77 ± 0.01 m) were enrolled in a randomized, double-blind, crossover design study. Subjects received a single dose of a MIPS (3 g of creatine, 2 g of arginine, 1 g of glutamine, 1 g of taurine, and 800 mg of β-alanine) or creatine citrate (CC) (3 g of creatine) or a placebo (PLA) in three successive trials 1 week apart. In a randomized order, participants consumed either MIPS, CC, or PLA and performed a REP 2 h later. Before ingestion and immediately after REP, subjects performed isometric contractions of the dominant biceps brachii: two maximal voluntary contractions (MVCs), followed by a 20% MVC for 90 s and a 60% MVC until exhaustion. Surface electromyographic indices of performance fatigability, conduction velocity (CV), and fractal dimension (FD) were obtained from the surface electromyographic signal (sEMG). Time to perform the task (TtT), basal blood lactate (BL), and BL after REP were also measured.

Results

Following REP, statistically significant (P < 0.05) pre–post mean for ΔTtT between MIPS (−7.06 s) and PLA (+0.222 s), ΔCV slopes (20% MVC) between MIPS (0.0082%) and PLA (−0.0519%) and for ΔCV slopes (60% MVC) between MIPS (0.199%) and PLA (−0.154%) were found. A pairwise comparison analysis showed no statistically significant differences in other variables between groups and condition vs. condition.

Conclusion

After REP, a creatine-enriched MIPS resulted in greater improvement of sEMG descriptors of performance fatigability and TtT compared with PLA. Conversely, no statistically significant differences in outcomes measured were observed between CC and PLA or MIPS and CC.
D-galactose Intake Alleviates Atopic Dermatitis in Mice by Modulating Intestinal Microbiota
Authors: Kim Dong-Yeon , Jung Do-Hyeon , Song Eun-Jung , Jang Ah-Ra , Park Ji-Yeon , Ahn Jae-Hun , Lee Tae-Sung , Kim Yeong-Jun , Lee Yun-Ji , Seo In-Su , Kim Hye-Eun , Ryu Eun-Ju , Sim Jaehyun , Park Jong-Hwan
Published: June 2022

Atopic dermatitis (AD) is one of the most prevalent, chronic and persistent inflammatory skin diseases closely associated with intestinal microbiota. To evaluate the effect of D-galactose intake on AD, we orally administered D-galactose to BALB/c mice whose ears and skin were treated with 2,4-dinitrochlorobenzene (DNCB). D-galactose alleviated DNCB-induced AD-like phenotypes such as redness, scaling/dryness and excoriation. Ear thickness was also decreased by D-galactose administration. Histopathological analysis revealed decreased epidermal thickening, infiltration of immune cells, especially mast cells, in the dermis. Total levels of serum IgE representing the immunological response of AD were decreased by D-galactose administration. Microbiota analysis showed that D-galactose administration restored gut microbiota profiles, which were altered in AD mice, characterized by increased abundance of Bacteroidetes and decreased abundance of Firmicutes. The increased abundance of Bacteroides and the decreased abundance of Prevotella and Ruminococcus were reversed by D-galactose treatment, following improvement of AD. Our results suggest the possible use of D-galactose as a prebiotic to alleviate AD by altering gut microbiota.
Development of a Deep Learning System to Detect Esophageal Cancer by Barium Esophagram
Authors: Zhang Peipei , She Yifei , Gao Junfeng , Feng Zhaoyan , Tan Qinghai , Min Xiangde , Xu Shengzhou
Published: June 2022

Background

Implementation of deep learning systems (DLSs) for analysis of barium esophagram, a cost-effective diagnostic test for esophageal cancer detection, is expected to reduce the burden to radiologists while ensuring the accuracy of diagnosis.

Objective

To develop an automated DLS to detect esophageal cancer on barium esophagram.

Methods

This was a retrospective study using deep learning for esophageal cancer detection. A two-stage DLS (including a Selection network and a Classification network) was developed. Five datasets based on barium esophagram were used for stepwise training, validation, and testing of the DLS. Datasets 1 and 2 were used to respectively train and test the Selection network, while Datasets 3, 4, and 5 were respectively used to train, validate, and test the Classification network. Finally, a positioning box with a probability value was outputted by the DLS. A region of interest delineated by experienced radiologists was selected as the ground truth to evaluate the detection and classification efficiency of the DLS. Standard machine learning metrics (accuracy, recall, precision, sensitivity, and specificity) were calculated. A comparison with the conventional visual inspection approach was also conducted.

Results

The accuracy, sensitivity, and specificity of our DLS in detecting esophageal cancer were 90.3%, 92.5%, and 88.7%, respectively. With the aid of DLS, the radiologists’ interpretation time was significantly shortened (Reader1, 45.7 s vs. 72.2 s without DLS aid; Reader2, 54.1 s vs. 108.7 s without DLS aid). Respective diagnostic efficiencies for Reader1 with and without DLS aid were 96.8% vs. 89.3% for accuracy, 97.5% vs. 87.5% for sensitivity, 96.2% vs. 90.6% for specificity, and 0.969 vs. 0.890 for AUC. Respective diagnostic efficiencies for Reader2 with and without DLS aid were 95.7% vs. 88.2% for accuracy, 92.5% vs. 77.5% for sensitivity, 98.1% vs. 96.2% for specificity, and 0.953 vs. 0.869 for AUC. Of note, the positioning boxes outputted by the DLS almost overlapped with those manually labeled by the radiologists on Dataset 5.

Conclusions

The proposed two-stage DLS for detecting esophageal cancer on barium esophagram could effectively shorten the interpretation time with an excellent diagnostic performance. It may well assist radiologists in clinical practice to reduce their burden.
A Multiparametric Method Based on Clinical and CT-Based Radiomics to Predict the Expression of p53 and VEGF in Patients With Spinal Giant Cell Tumor of Bone
Authors: Wang Qizheng , Zhang Yang , Zhang Enlong , Xing Xiaoying , Chen Yongye , Nie Ke , Yuan Huishu , Su Min-Ying , Lang Ning
Published: June 2022

Purpose

This project aimed to assess the significance of vascular endothelial growth factor (VEGF) and p53 for predicting progression-free survival (PFS) in patients with spinal giant cell tumor of bone (GCTB) and to construct models for predicting these two biomarkers based on clinical and computer tomography (CT) radiomics to identify high-risk patients for improving treatment.

Material and Methods

A retrospective study was performed from April 2009 to January 2019. A total of 80 patients with spinal GCTB who underwent surgery in our institution were identified. VEGF and p53 expression and clinical and general imaging information were collected. Multivariate Cox regression models were used to verify the prognostic factors. The radiomics features were extracted from the regions of interest (ROIs) in preoperative CT, and then important features were selected by the SVM to build classification models, evaluated by 10-fold crossvalidation. The clinical variables were processed using the same method to build a conventional model for comparison.

Results

The immunohistochemistry of 80 patients was obtained: 49 with high-VEGF and 31 with low-VEGF, 68 with wild-type p53, and 12 with mutant p53. p53 and VEGF were independent prognostic factors affecting PFS found in multivariate Cox regression analysis. For VEGF, the Spinal Instability Neoplastic Score (SINS) was greater in the high than low groups, p < 0.001. For p53, SINS (p = 0.030) and Enneking stage (p = 0.017) were higher in mutant than wild-type groups. The VEGF radiomics model built using 3 features achieved an area under the curve (AUC) of 0.88, and the p53 radiomics model built using 4 features had an AUC of 0.79. The conventional model built using SINS, and the Enneking stage had a slightly lower AUC of 0.81 for VEGF and 0.72 for p53.

Conclusion

p53 and VEGF are associated with prognosis in patients with spinal GCTB, and the radiomics analysis based on preoperative CT provides a feasible method for the evaluation of these two biomarkers, which may aid in choosing better management strategies.
Research Progress in Exosome-Based Nanoscale Drug Carriers in Tumor Therapies
Authors: Fu Wei , Li Tingting , Chen Hongbo , Zhu Shu , Zhou Changkai
Published: June 2022

Current antitumor treatment methods have several reported limitations, including multidrug resistance and serious adverse reactions. Targeted drug delivery systems are effective alternatives that can help healthcare providers overcome these limitations. Exosomes can serve as a natural nanoscale drug delivery system, with the advantages of high biocompatibility, low immunogenicity, and efficient tumor targetability. In this paper, we discuss the biological characteristics of exosomes, summarize the drug-carrying mechanisms of exosome-based drug delivery systems, and examine the potential role and applicability of exosomes in clinical tumor treatment approaches. This review can be used as a guideline for the future development of exosome-based delivery systems in clinical precision tumor treatment.
Anxiety and Depression in Adults With Congenital Heart Disease
Authors: Lebherz Corinna , Frick Michael , Panse Jens , Wienstroer Philipp , Brehmer Katrin , Kerst Gunter , Marx Nikolaus , Mathiak Klaus , Hövels-Gürich Hedwig
Published: June 2022

Introduction

Anxiety and depression can worsen outcome in patients with heart disease. We elucidate the prevalence of anxiety and depression in a cohort of adults with congenital heart disease (ACHD).

Materials and Methods

Prospective screening for anxiety or depression was performed in 204 consecutive patients of the outpatient clinic of our tertiary care center using the Hospital Anxiety and Depression Scale (HADS) questionnaire and the distress thermometer (DT) as a potential ultra-short screening test. Functional data were assessed at liberty of the responsible physician. HADS scores ≥ 8 were considered doubtful and scores ≥ 11 as confirmed cases of anxiety or depression, respectively. HADS results were compared with a historical group of 100 patients with non-Hodgkin Lymphoma (NHL) as well as German reference values from the literature.

Results

Patients from the ACHD cohort were 28 ± 10 years old (mean ± SD, 54% male), 34% had a simple, 51% a moderate, including 52 patients with transposition of the great arteries after arterial switch operation, and 15% a heart defect of severe complexity. Prevalence of depression in ACHD was comparable to the German normal population (5.9% ACHD vs. 5.4% control). In contrast, prevalence of anxiety was higher than expected from reference values (12.7% ACHD vs. 5.6% control). There was a positive association between psychological distress and NYHA class [anxiety: OR 2.67 (95% CI, 1.50–4.76) p = 0.001; depression: OR 2.93 (95% CI, 1.60–5.35) p = 0.0005], but not with age, gender, or heart defect severity. Percentages of patients with ACHD with anxiety were significantly higher than in a cohort of patients with indolent non-Hodgkin lymphoma (NHL) but comparable to those with aggressive NHL (HADS-A ≥ 11: ACHD 12.7%, indolent NHL 2.2%, aggressive NHL 13.2%; p = 0.037 ACHD vs. indolent NHL; p = 0.929 ACHD vs. aggressive NHL). The distress thermometer screening test had only a fair discriminatory ability (AUC 0.708; p = 0.002) and is therefore of limited usability.

Conclusion

Adults with congenital heart disease exhibit an increased risk for anxiety disorders independently of the severity of the underlying heart defect. Anxiety prevalence was comparable to a historical cohort of patients with aggressive NHL underlining the importance of a routine screening for psychosocial distress in adults with congenital heart disease.
The RVP Method—From Real Ab-Initio Calculations to Complex Energies and Transition Dipoles
Authors: Landau Arie , Haritan Idan , Moiseyev Nimrod
Published: June 2022

The purpose of this review is to describe the rationale behind the RVP (resonanceviaPadé) approach for calculating energies and widths of resonances, while emphasizing a solid mathematical ground. The method takes real input data from stabilization graphs, where quasi-discrete continuum energy levels are plotted as a function of a parameter, which gradually makes the employed basis functions more diffuse. Thus, input data is obtained from standard quantum chemistry packages, which are routinely used for calculating molecular bound electronic states. The method simultaneously provides the resonance positions (energies) and widths (decay rates)viaanalytical continuations of real input data into the complex plane (viathe Padé approximant). RVP holds for isolated resonances (in which the energy-gap between resonance states is smaller than their decay rates). We focus also on the ability to use an open-source “black-box” code to calculate the resonance positions and widths as well as other complex electronic properties, such as transition dipoles.
Ambient Fluid Rheology Modulates Oscillatory Instabilities in Filament-Motor Systems
Authors: Tamayo Joshua , Mishra Anupam , Gopinath Arvind
Published: June 2022

Semi-flexible filaments interacting with molecular motors and immersed in rheologically complex and viscoelastic media constitute a common motif in biology. Synthetic mimics of filament-motor systems also feature active or field-activated filaments. A feature common to these active assemblies is the spontaneous emergence of stable oscillations as a collective dynamic response. In nature, the frequency of these emergent oscillations is seen to depend strongly on the viscoelastic characteristics of the ambient medium. Motivated by these observations, we study the instabilities and dynamics of a minimal filament-motor system immersed in model viscoelastic fluids. Using a combination of linear stability analysis and full non-linear numerical solutions, we identify steady states, test the linear stability of these states, derive analytical stability boundaries, and investigate emergent oscillatory solutions. We show that the interplay between motor activity, filament and motor elasticity, and fluid viscoelasticity allows for stable oscillations or limit cycles to bifurcate from steady states. When the ambient fluid is Newtonian, frequencies are controlled by motor kinetics at low viscosities, but decay monotonically with viscosity at high viscosities. In viscoelastic fluids that have the same viscosity as the Newtonian fluid, but additionally allow for elastic energy storage, emergent limit cycles are associated with higher frequencies. The increase in frequency depends on the competition between fluid relaxation time-scales and time-scales associated with motor binding and unbinding. Our results suggest that both the stability and oscillatory properties of active systems may be controlled by tailoring the rheological properties and relaxation times of ambient fluidic environments.
Comparative Transcriptome and Proteome Analysis Provides New Insights Into the Mechanism of Protein Synthesis in Kenaf (Hibiscus cannabinus L.) Leaves
Authors: Zhang Chao , Deng Yong , Zhang Gaoyang , Li Jianjun , Xiao Aiping , Zhao Lining , Chen Anguo , Tang Huijuan , Chang Li , Pan Gen , Wu Yingbao , Zhang Jiangjiang , Zhang Cuiping , Birhanie Ziggiju Mesenbet , Li Hui , Wu Juan , Yang Dawei , Li Defang , Huang Siqi
Published: June 2022

Given the rising domestic demand and increasing global prices of corn and soybean, China is looking for alternatives for these imports to produce animal fodder. Kenaf (Hibiscus cannabinus L.) has great potential as a new forage source, due to abundant proteins, phenols and flavonoids in its leaves. However, few studies have evaluated the mechanism of protein synthesis in kenaf leaves. In the current work, compared with kenaf material “L332,” the percentage of crude protein content in leaves of material “Q303” increased by 6.13%; combined with transcriptome and proteome data, the kenaf samples were systematically studied to obtain mRNA-protein correlation. Then, the genes/proteins related to protein synthesis in the kenaf leaves were obtained. Moreover, this work detected mRNA expression of 20 differentially expressed genes (DEGs). Meanwhile, 20 differentially expressed proteins (DEPs) related to protein synthesis were performed parallel reaction monitoring. Fructose-1,6-bisphosphatase (FBP), nitrite reductase (NirA), prolyl tRNA synthase (PARS) and glycine dehydrogenase (GLDC) presented increased mRNA and protein levels within kenaf leaves with high protein content. Based on the obtained findings, FBP, NirA, PARS, and GLDC genes may exert a vital function in the protein synthesis of kenaf leaves. The results provide a new idea for further studying the potential genes affecting the quality trait of protein content in kenaf leaves and provide gene resources and a theoretical foundation for further cultivating high protein kenaf varieties.