bluuebunny/crossref_metadata_2025 huggingface dataset:
The Bicentenary of Bell’s Description of the Neuroanatomical Basis of Facial Paralysis: Historical Remarks
Authors: Cantarella Giovanna , Mazzola Riccardo F.
Published: July 2021

Charles Bell was a talented and versatile Scottish anatomist, neurophysiologist, artist, and surgeon. On July 12, 1821, he reported his studies regarding facial innervation in the essay “On the Nerves,” read before the Royal Society in London. Since then, idiopathic peripheral facial paralysis has been named “Bell’s palsy.” He was the first author to describe the neuroanatomical basis of facial paralysis, in an essay enriched by beautifully self‐made illustrations. The aim of this article is to trace the history of Bell’s description of the neuroanatomy of the facial nerve, reexamining his 1821 article, in which he stated that the lower facial expression muscles were dually innervated by both the fifth and seventh cranial nerves. In 1829, he rectified this conclusion, recognizing the exclusive role of the facial nerve, which he defined as the “respiratory nerve.” We offer a tribute to this polymath scientist on the bicentenary of his 1821 publication.
Otolaryngologist Performance in the Merit‐Based Incentive Payment System in 2018
Authors: Miller Lauren E. , Kondamuri Neil S. , Xiao Roy , Rathi Vinay K.
Published: July 2021

In 2017, the Centers for Medicare and Medicaid Services transitioned clinicians to the Merit‐Based Incentive Payment System (MIPS), the largest mandatory pay‐for‐performance program in health care history. The first full MIPS program year was 2018, during which the Centers for Medicare and Medicaid Services raised participation requirements and performance thresholds. Using publicly available Medicare data, we conducted a retrospective cross‐sectional analysis of otolaryngologist participation and performance in the MIPS in 2017 and 2018. In 2018, otolaryngologists reporting as individuals were less likely (P <. 001) to earn positive payment adjustments (n = 1076/1584, 67.9%) than those participating as groups (n = 2802/2804, 99.9%) or in alternative payment models (n = 1705/1705, 100.0%). Approximately one‐third (n = 1286/4472, 28.8%) of otolaryngologists changed reporting affiliations between 2017 and 2018. Otolaryngologists who transitioned from reporting as individuals to participating in alternative payment models (n = 137, 3.1%) achieved the greatest performance score improvements (median change, +23.4 points; interquartile range, 12.0‐65.5). These findings have important implications for solo and independent otolaryngology practices in the era of value‐based care.
Effects of probiotic and synbiotic supplementation on insulin resistance in women with polycystic ovary syndrome: a meta-analysis
Authors: Miao Chenyun , Guo Qingge , Fang Xiaojie , Chen Yun , Zhao Ying , Zhang Qin
Published: July 2021

Objective

This meta-analysis evaluated the effect of probiotics and synbiotics on insulin resistance in patients with polycystic ovary syndrome (PCOS).

Methods

A systematic search was performed to identify all relevant publications listed on the electronic databases (PubMed®, Web of Science, Embase® and China National Knowledge Infrastructure) between inception and 30 October 2020. All statistical analyses were performed on randomized controlled trials (RCTs) using RevMan version 5.3 software provided by the Cochrane Collaboration.

Results

A total of 486 patients from seven RCTs were included in the meta-analysis. Probiotic and synbiotic supplementation appeared to improve levels of homeostatic model assessment of insulin resistance (mean difference = –0.37; 95% confidence interval –0.69, –0.05) and serum insulin (standardized mean difference = –0.66; 95% confidence interval –1.19, –0.12). The results failed to show any influence of probiotic and synbiotic supplementation on body mass index, waist circumference, hip circumference and fasting blood sugar.

Conclusions

Probiotics and synbiotics appear to have a partially beneficial effect on indices of insulin resistance in patients with PCOS.
Culvert Inspection Vehicle with Improved Telemetry Range
Authors: Burton Jonathan , Orfeo Daniel J , Griswold Logan , Stanley Steven K , Redmond Michelle , Xia Tian , Huston Dryver
Published: July 2021

Proper inspection of small culverts can prevent roadway failures, traffic disturbances, and save tens of thousands of dollars on costly repairs. The Vermont Agency of Transportation (VTrans) has adopted a policy that requires all culverts to be inspected every 5 years. Because of this, approximately 9,600 small culverts must be inspected annually. In this study, a lightweight inspection vehicle was designed, built, and tested to meet VTrans requirements for efficient and affordable small culvert inspection. Optimal parameters for video transmission through small culverts were understood through theory and a series of field tests. Vehicle form factor was chosen for maneuverability through small, flooded culverts. Performance for drop inlet inspection scenarios is characterized and discussed. Compared with prior designs, the “Hydraulic Inspection Vehicle Explorer (HIVE) 2.0” inspection vehicle offered much greater video telemetry range and superior maneuverability.
Influences of Gesture-Based Mobile Phone Use While Driving
Authors: Niu Jianwei , Zhou Yulin , Wang Dan , Liu Xingguo
Published: July 2021

The use of mobile phones while driving has been a hot topic in the field of driving safety for decades. Although there are few studies on the influence of gesture control on in-vehicle secondary tasks, this study aims to investigate the impact of gesture-based mobile phone use without touching while driving from the perspective of multiple-resource workload owing to visual, auditory, cognitive, and psychomotor resource occupation. A novel gesture control technique was adopted for secondary task interactions, to recognize the gestures of drivers. An experiment was conducted to study the influences of two interaction modes, traditional touch-based mobile phone interaction and gesture-based mobile phone interaction, on driving behavior in three different cognitive level task groups. The results indicate that gesture-based mobile phone interaction can improve driving performance with regard to lateral position-keeping ability and steering wheel control; nevertheless, it has no significant impact on longitudinal metrics such as driving speed, driving speed variation, and throttle control variation. Gesture-based mobile phone interactions have a larger effect on secondary tasks with medium cognitive load but not on actual operation tasks. It was also verified that the performance of gesture-based mobile phone interaction was better in secondary mobile phone tasks such as switching (e.g., switching songs) and adjusting (e.g., adjusting volume) than the traditional interaction mode. This study provides the theoretical and experimental support for human–computer interaction using gesture-based mobile phone interactive control in future automobiles.
Evaluating the Benefits of Red-Light Violation Warning System in a Connected Vehicle Simulation Environment
Authors: Hadi Mohammed , Amine Kamar , Hunsanon Thodsapon , Arafat Mahmoud
Published: July 2021

The rapid development of connected vehicle (CV) and cooperative automated vehicle (CAV) technologies in recent years calls for the assessment of the impacts of these technologies on system performance. Microscopic simulation can play a major role in assessing these impacts, particularly during the early stages of the adoption of the technologies and associated applications. This study develops a method to evaluate the safety benefits of red-light violation warning (RLVW), a CV-based vehicle-to-infrastructure (V2I) application at signalized intersections, utilizing simulation. The study results confirm that it is critical to calibrate the probability to stop on amber in the utilized simulation model to reflect real-world driver behaviors when assessing RLVW impacts. Without calibration, the model is not able to assess the benefits of RLVW in reducing RLR and right-angle conflicts. Based on a surrogate safety assessment, the calibrated simulation models result shows that the CV-based RLVW can enhance the safety at signalized intersections by approximately 50.7% at 100% utilization rate of the application, considering rear-end, and right-angle conflicts.
Daily Traffic Count Imputation for Bicycle and Pedestrian Traffic: Comparing Existing Methods with Machine Learning Approaches
Authors: Roll Josh
Published: July 2021

Monitoring nonmotorized traffic is becoming increasingly common practice at local and state departments of transportation. These travel activity data are necessary to monitor the system and track progress toward active transportation policy and program goals. A common problem is that permanent count site data are often missing, making those sites less useful. Being able to accurately estimate those missing data records functionally increases the amount of data available to use by themselves as metrics for monitoring traffic but also makes available more data for factoring short-term sites. Using nonmotorized traffic counts from several cities in Oregon, this research compared the ability of day-of-year (DOY) factors, a statistical model, and machine learning algorithms to accurately impute daily traffic records for annual traffic estimation. Based on exhaustive cross-validation experiments using data not missing at random scenarios, this research concluded that random forest and DOY factor approaches could be used to impute daily counts for nonmotorized traffic but each approach comes with tradeoffs. Though for many missing data scenarios random forest performed best, this method is complicated to estimate and apply. DOY factor-based methods are simpler to create and apply, and though more accurate in scenarios with significant amounts of missing data, they were less flexible given the need for data from neighboring count sites. Negative binomial regression was also found to work well in scenarios with moderate to low amounts of missing data. This work can inform nonmotorized traffic count programs needing vetted solutions for traffic data imputation.
Computational Thinking Through an Empirical Lens: A Systematic Review of Literature
Authors: Ezeamuzie Ndudi O. , Leung Jessica S. C.
Published: July 2021

This article provides an overview of the diverse ways in which computational thinking has been operationalised in the literature. Computational thinking has attracted much interest and debatably ranks in importance with the time-honoured literacy skills of reading, writing, and arithmetic. However, learning interventions in this subject have modelled computational thinking differently. We conducted a systematic review of 81 empirical studies to examine the nature, explicitness, and patterns of definitions of computational thinking. Data analysis revealed that most of the reviewed studies operationalised computational thinking as a composite of programming concepts and preferred definitions from assessment-based frameworks. On the other hand, a substantial number of the studies did not establish the meaning of computational thinking when theorising their interventions nor clearly distinguish between computational thinking and programming. Based on these findings, this article proposes a model of computational thinking that focuses on algorithmic solutions supported by programming concepts which advances the conceptual clarity between computational thinking and programming.
Progress of biomaterials for bone tumor therapy
Authors: Chen Hanzheng , Yao Yongchang
Published: July 2021

Bone tumors are currently a major clinical challenge. In recent decades, strategies using well-designed versatile biomaterials for the treatment of bone tumors have emerged and attracted extensive research interest. Suitable biomaterials not only facilitate repair for bone defects aroused by surgical intervention but also help deliver antineoplastic drugs to the target site or provide photothermal/magnetothermal therapy to kill bone tumor cells. Thus, the development of biomaterials exhibits a great perspective for future bone tumor treatment.

We summarize the recent progress of versatile biomaterials for bone tumor therapy, with an emphasis on photothermal/magnetothermal therapy and drug delivery.

With the further understanding and development of biomaterials, multifunctional biomaterials have been proposed for bone tumor treatment. Through the interdisciplinary cooperation from the fields of biomedicine, clinical medicine and engineering, multifunctional biomaterials will perfectly match individual bone defects in the clinic with low cost in the future.
Realigning Expectations With Reality: A Case Study on Maternal Mental Health During a Difficult Breastfeeding Journey
Authors: Elder Mason , Murphy Lorann , Notestine Stacy , Weber Ashley
Published: July 2021

Introduction:

Many mothers have the goal to breastfeed. However, more than 50% will have breastfeeding difficulty by the 3rd day of life. Mothers who are unable to meet their breastfeeding goals are at higher risk for anxiety, depression, embarrassment, and guilt. Those who stop breastfeeding need support and help resolving these feelings. This case study aims to describe one woman’s difficulty with mental health surrounding breastfeeding, her decision to bottle feed, and her successful transition back to direct breastfeeding.

Main Issue:

Barriers to the participant’s success with breastfeeding were pre-existing history of depression/anxiety, forceps delivery, uncontrolled perineal pain, infant physical trauma, and nipple/flow confusion. The decision to discontinue direct breastfeeding and start bottle feeding came after 2 months of anxiety, frustration, and persistence.

Management:

The participant followed her healthcare team’s recommendations of triple feeding, lactation support groups, pediatric chiropractic adjustments, and prescribed galactagogues. After 2 months of exhaustion and deliberation, she made the difficult decision to stop breastfeeding for nutritional benefits and switched to breastfeeding only for her infant’s pleasure and comfort. Lowered expectations allowed the dyad to heal and her son to transition to nearly exclusive breastfeeding at 4 months of life.

Conclusion:

Clinicians must be aware of the delicate balance between promoting breastfeeding for its nutritional value and health benefits and supporting a struggling mother with mental health needs.
Interest Incongruence and Job Performance: Examining the Moderating Roles of Job Crafting and Positive Affect
Authors: Li Junyi , Yang Hui , Weng Qingxiong , Gao Wenyang
Published: July 2021

Interest incongruence between employees and work environments has been considered as an adverse working condition; however, the way employees cope with it has rarely been explored. Using the conservation of resources theory, the appraisal theory, and the broaden-and-build theory, this study aims to investigate the moderating roles of job crafting and trait positive affect, separately and interactively, in the relationship between interest incongruence and job performance. Data collected from 384 Chinese employees and their colleagues across two time periods supported our hypotheses. Specifically, findings indicated that the relationship between interest incongruence and job performance was weakened when employees were more engaged in job crafting, or for employees with high positive affect. More importantly, a three-way interaction suggested that the detrimental impact of interest incongruence on job performance was especially mitigated when both job crafting and positive affect were high. Future studies should consider the combined roles of employees’ proactive behaviors and trait affectivity in improving job performance.
Moving from Feedback to Feedforward in IBDP classrooms
Authors: Dulfer Nicky , Akhlaghi Koopaei Firoozeh
Published: July 2021

There is widespread acceptance of the positive impact of constructive feedback on students’ learning progress. However, few studies investigate the role of feedforward in high-stakes learning environments. This research explores feedback and feedforward practices in International Baccalaureate Diploma Programme classrooms in Hong Kong and Australia. The article analyses 18 teachers’ practices and perceptions about feedback and feedforward. The teachers’ perceptions on feedforward were analysed using a survey and semi-structured interviews, while their teaching practices were evaluated using a lesson observation instrument. Results indicated that participants were aware of the importance of providing feedforward techniques and tools in the classroom to support students in closing the gaps between their current performance and desired performance. Not all teachers, however, incorporated feedforward in all their lessons as a learning tool or differentiation strategy to enhance students’ learning experience and assessment outcomes.
Education of Students with Disabilities, Science, and Randomized Controlled Trials
Authors: Odom Samuel L.
Published: July 2021

The purpose of this article is to examine the application of randomized controlled trial (RCT) methodology for determining the efficacy of school-based interventions in general and special education. In education science, RCTs are widely acknowledged as the gold standard of efficacy research, with other methodologies relegated to a lower level of credibility. However, scholars from different disciplines have raised a variety of issues with RCT methodology, such as the utility of random assignment, external validity, and the challenges of applying the methodology for assessing complex service interventions, which are necessary for many students with disabilities. Also, scholars have noted that school-based RCT studies have largely generated low effect sizes, which indicate that the outcomes of the interventions do not differ substantially from services as usual. The criticisms of RCT studies as the primary methodology in school-based intervention research for students with disabilities are offered along with recommendations for extending the acceptability of a broader variety of research approaches.
Condition-based maintenance in hydroelectric plants: A systematic literature review
Authors: de Santis Rodrigo Barbosa , Gontijo Tiago Silveira , Costa Marcelo Azevedo
Published: July 2021

Industrial maintenance has become an essential strategic factor for profit and productivity in industrial systems. In the modern industrial context, condition-based maintenance guides the interventions and repairs according to the machine’s health status, calculated from monitoring variables and using statistical and computational techniques. Although several literature reviews address condition-based maintenance, no study discusses the application of these techniques in the hydroelectric sector, a fundamental source of renewable energy. We conducted a systematic literature review of articles published in the area of condition-based maintenance in the last 10 years. This was followed by quantitative and thematic analyses of the most relevant categories that compose the phases of condition-based maintenance. We identified a research trend in the application of machine learning techniques, both in the diagnosis and the prognosis of the generating unit’s assets, being vibration the most frequently discussed monitoring variable. Finally, there is a vast field to be explored regarding the application of statistical models to estimate the useful life, and hybrid models based on physical models and specialists’ knowledge, of turbine-generators.
Mitochondrial dysfunction and liver disease: role, relevance, and potential for therapeutic modulation
Authors: Middleton Paul , Vergis Nikhil
Published: July 2021

Mitochondria are key organelles involved in energy production as well as numerous metabolic processes. There is a growing interest in the role of mitochondrial dysfunction in the pathogenesis of common chronic diseases as well as in cancer development. This review will examine the role mitochondria play in the pathophysiology of common liver diseases, including alcohol-related liver disease, non-alcoholic fatty liver disease, chronic hepatitis B and hepatocellular carcinoma. Mitochondrial dysfunction is described widely in the literature in studies examining patient tissue and in disease models. Despite significant differences in pathophysiology between chronic liver diseases, common mitochondrial defects are described, including increased mitochondrial reactive oxygen species production and impaired oxidative phosphorylation. We review the current literature on mitochondrial-targeted therapies, which have the potential to open new therapeutic avenues in the management of patients with chronic liver disease.
The Italian version of the Unité Rhumatologique des Affections de la Main (URAM) for Dupuytren’s disease: The URAM-I(10)
Authors: Lanfranchi E , Fairplay T , Arcuri P , Lando M , Marinelli F , Pillastrini P , Vanti C
Published: July 2021

Introduction

Several general hand functional assessment tools for Dupuytren’s disease have been reported, but none of the patient-reported-outcome measures specific to Dupuytren’s disease-associated disabilities are available in the Italian language. The purpose of this study was to culturally adapt the Unité Rhumatologique des Affections de la Main (URAM) into Italian (URAM-I) and determine its measurement properties.

Methods

Cross-cultural adaptation was performed according to the current guidelines. Construct validity (convergent and divergent validity) was measured by comparing the URAM-I with the Pain-Rated Wrist/Hand Evaluation (PRWHE-I), Short-Form 36 (SF-36-I) scale and finger range of motion, respectively. Factor analysis was used to investigate the URAM-I’s internal structure. Reliability was assessed by internal consistency (Cronbach’s alpha) and test-retest reliability by Intra-Class Correlation Coefficient (ICC).

Results

This study included 96 patients (males = 85%, age = 66.8 ± 9.3). Due to the cultural adaptation, we divided the original item #1 into two separate items, thus generating the URAM-I(10). Convergent validity analysis showed a strong positive (r = 0.67), significant (p < 0.01) Pearson’s correlation with the PRWHE-I. Divergent validity analysis showed a weak, negative (r < 0.3) and not significant correlation with the SF-36-I subscales, except for the physical pain subscale (r = −0.21, p < 0.05). Factor analysis revealed a 2-factor, 4-item solution that explained 76% of the total variance. The URAM-I(10) demonstrated high internal consistency (α = 0.94) and high test-retest reliability (ICC = 0.97).

Conclusion

The URAM-I(10) demonstrates moderate construct validity, high internal consistency and test-retest reliability, and showed a 2-factor internal structure. Its evaluative use can be suggested for the Italian Dupuytren’s population.
Factors affecting earthquake responders’ building damage information needs and use
Authors: Bhattacharjee Gitanjali , Soden Robert , Barns Karen , Loos Sabine , Lallemant David
Published: July 2021

After an earthquake, many responding organizations need to understand the scale and distribution of building damage to react effectively. However, their building damage information needs and information use remain poorly understood, limiting the efficacy of information production, sharing, and research. To clarify those needs, we conducted a two-part survey, comprising semi-structured interviews and an online questionnaire, of building damage information users and providers. Based on the interview data and questionnaire responses, we characterize six post-disaster tasks that rely on building damage information by their timing and by the necessary qualities of the information they require. Through inductive analysis of the interview data, we show that responders’ use of building damage information also depends on factors beyond the building damage information itself—namely, trust, impediments to information sharing, their varying understandings of disaster, and their attitudes toward emerging technologies. These factors must be considered in the design of any effort to create and/or disseminate post-disaster building damage information.
Phase 2 study of danicopan in patients with paroxysmal nocturnal hemoglobinuria with an inadequate response to eculizumab
Authors: Kulasekararaj Austin G. , Risitano Antonio M. , Maciejewski Jaroslaw P. , Notaro Rosario , Browett Peter , Lee Jong Wook , Huang Mingjun , Geffner Michael , Brodsky Robert A.
Published: July 2021

Paroxysmal nocturnal hemoglobinuria (PNH) is characterized by uncontrolled terminal complement activation and subsequent intravascular hemolysis (IVH). C5 inhibitors prevent membrane attack complex formation, but patients may experience extravascular hemolysis (EVH) and continue to require blood transfusions. Danicopan, an oral proximal complement inhibitor of alternative pathway factor D (FD), is designed to control IVH and EVH. In a phase 2 dose-finding trial, eculizumab-treated transfusion-dependent patients with PNH (n = 12) received danicopan, 100 to 200 mg thrice daily, in addition to their eculizumab regimen for 24 weeks. End points included hemoglobin (Hgb) change vs baseline at week 24 (primary), reduction in blood transfusions, and patient-reported outcomes. Safety, tolerability, and pharmacokinetics/pharmacodynamics were measured. Twelve patients received ≥1 danicopan dose; 1 patients discontinued from a serious adverse event deemed unlikely related to danicopan. Eleven patients completed the 24-week treatment period. Addition of danicopan resulted in a mean Hgb increase of 2.4 g/dL at week 24. In the 24 weeks prior to danicopan, 10 patients received 31 transfusions (50 units) compared with 1 transfusion (2 units) in 1 patient during the 24-week treatment period. Mean Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue score increased by 11 points from baseline to week 24. The most common adverse events were headache, cough, and nasopharyngitis. Addition of danicopan, a first-in-class FD inhibitor, led to a meaningful improvement in Hgb and reduced transfusion requirements in patients with PNH who were transfusion-dependent on eculizumab. These benefits were associated with improvement of FACIT-Fatigue. This trial was registered at www.clinicaltrials.gov as #NCT03472885.
Repeated oxytocin prevents central sensitization by regulating synaptic plasticity via oxytocin receptor in a chronic migraine mouse model
Authors: Wang Yunfeng , Pan Qi , Tian Ruimin , Wen Qianwen , Qin Guangcheng , Zhang Dunke , Chen Lixue , Zhang Yixin , Zhou Jiying
Published: July 2021

Background

Central sensitization is one of the characters of chronic migraine (CM). Aberrant synaptic plasticity can induce central sensitization. Oxytocin (OT), which is a hypothalamic hormone, plays an important antinociceptive role. However, the antinociceptive effect of OT and the underlying mechanism in CM remains unclear. Therefore, we explored the effect of OT on central sensitization in CM and its implying mechanism, focusing on synaptic plasticity.

Methods

A CM mouse model was established by repeated intraperitoneal injection of nitroglycerin (NTG). Von Frey filaments and radiant heat were used to measure the nociceptive threshold. Repeated intranasal OT and intraperitoneal L368,899, an oxytocin receptor (OTR) antagonist, were administered to investigate the effect of OT and the role of OTR. The expression of calcitonin gene-related peptide (CGRP) and c-fos were measured to assess central sensitization. N-methyl D-aspartate receptor subtype 2B (NR2B)-regulated synaptic-associated proteins and synaptic plasticity were explored by western blot (WB), transmission electron microscope (TEM), and Golgi-Cox staining.

Results

Our results showed that the OTR expression in the trigeminal nucleus caudalis (TNC) of CM mouse was significantly increased, and OTR was colocalized with the postsynaptic density protein 95 (PSD-95) in neurons. Repeated intranasal OT alleviated the NTG-induced hyperalgesia and prevented central sensitization in CM mouse. Additionally, the OT treatment inhibited the overexpression of phosphorylated NR2B and synaptic-associated proteins including PSD-95, synaptophysin-1 (syt-1), and synaptosomal-associated protein 25 (snap25) in the TNC of CM mouse and restored the abnormal synaptic structure. The protective effect of OT was prevented by L368,899. Furthermore, the expression of adenylyl cyclase 1 (AC1)/ protein kinase A (PKA)/ phosphorylation of cyclic adenosine monophosphate response element-binding protein (pCREB) pathway was depressed by OT and restored by L368,899.

Conclusions

Our findings demonstrate that repeated intranasal OT eliminates central sensitization by regulating synaptic plasticity via OTR in CM. The effect of OT has closely associated with the down-regulation of AC1/PKA/pCREB signaling pathway, which is activated in CM model. Repeated intranasal OT may be a potential candidate for CM prevention.
Mixture toxic impacts and the related mechanism of aflatoxin B1 and deoxynivalenol on embryonic zebrafish (Danio rerio)
Authors: Wang Yanhua , Wang Qiang , Ji Chun , Guo Xiaoxuan , Yang Guiling , Wang Dou , Weng Hongbiao , Qian Yongzhong , Chen Chen
Published: July 2021

Background

Although humans and animals are often simultaneously exposed to a variety of mycotoxins via feed and food consumption, in which aflatoxin B1 (AFB1) and deoxynivalenol (DON) is one of the most prevalent combination of mycotoxins. Many toxicological studies have merely focused on the impacts of single mycotoxins. In the present study, the combined toxicity and the related mechanism of AFB1 and DON to zebrafish (Danio rerio) were investigated.

Results

Results exhibited that DON had lower toxicity to embryonic zebrafish with a 7-day LC50of 218.3 mg a.i. L−1in comparison to AFB1 (0.031 mg a.i. L−1). The mixture of AFB1 and DON elicited an additive combined effect on zebrafish embryos. The levels of CAT, caspase-3, and T4 markedly varied in most single and mixture groups. The expressions of four genes (cas3,apaf-1,cc-chem,andcyp19a) associated with oxidative stress, cellular apoptosis, immune system, and endocrine system were markedly varied upon the mixture exposure in comparison to the corresponding single exposure of AFB1 or DON.

Conclusions

Our results revealed that the impacts of a mixture could not be estimated solely based on toxicities of the single mycotoxins. Taken together, our comprehensive investigation on the mycotoxin mixtures and their potential mechanisms could better reflect the reality of mycotoxin contamination in food and feed.
Determination of genetic effects and functional SNPs of bovine HTR1B gene on milk fatty acid traits
Authors: Cao Mingyue , Shi Lijun , Peng Peng , Han Bo , Liu Lin , Lv Xiaoqing , Ma Zhu , Zhang Shengli , Sun Dongxiao
Published: July 2021

Background

Our previous genome-wide association study (GWAS) on milk fatty acid traits in Chinese Holstein cows revealed, the SNP, BTB-01556197, was significantly associated with C10:0 at genome-wide level (P = 0.0239). It was located in the down-stream of 5-hydroxytryptamine receptor 1B (HTR1B) gene that has been shown to play an important role in the regulation of fatty acid oxidation. Hence, we considered it as a promising candidate gene for milk fatty acids in dairy cattle. In this study, we aimed to investigate whether the HTR1B gene had significant genetic effects on milk fatty acid traits.

Results

We re-sequenced the entire coding region and 3000 bp of 5′ and 3′ flanking regions of HTR1B gene. A total of 13 SNPs was identified, containing one in 5′ flanking region, two in 5′ untranslated region (UTR), two in exon 1, five in 3′ UTR, and three in 3′ flanking region. By performing genotype-phenotype association analysis with SAS9.2 software, we observed that 13 SNPs were significantly associated with medium-chain saturated fatty acids such as C6:0, C8:0 and C10:0 (P < 0.0001 ~ 0.042). With Haploview 4.1 software, linkage disequilibrium (LD) analysis was performed. Two haplotype blocks formed by two and ten SNPs were observed. Haplotype-based association analysis indicated that both haplotype blocks were strongly associated with C6:0, C8:0 and C10:0 as well (P < 0.0001 ~ 0.0071). With regards to the missense mutation in exon 1 (g.17303383G > T) that reduced amino acid change from alanine to serine, we predicted that it altered the secondary structure of HTR1B protein with SOPMA. In addition, we predicted that three SNPs in promoter region, g.17307103A > T, g.17305206 T > G and g.17303761C > T, altered the binding sites of transcription factors (TFs) HMX2, PAX2, FOXP1ES, MIZ1, CUX2, DREAM, and PPAR-RXR by Genomatix. Of them, luciferase assay experiment further confirmed that the allele T of g.17307103A > T significantly increased the transcriptional activity of HTR1B gene than allele A (P = 0.0007).

Conclusions

In conclusion, our findings provided first evidence that the HTR1B gene had significant genetic effects on milk fatty acids in dairy cattle.
Dynamic changes of miRNAs in skeletal muscle development at New Zealand rabbits
Authors: Jing Jing , Jiang Xichun , Zhu Cuiyun , Zheng Qi , Ji Qianyun , Yin Huiqun , Huang Jingtong , Zhu Yixiao , Wang Jiao , Qin Shuaiqi , Ling Yinghui
Published: July 2021

Background

miRNA is one of the crucial roles in the complex and dynamic network that regulates the development of skeletal muscle. The landscape of skeletal muscle miRNAs from fetus to adult in New Zealand rabbits has not been revealed yet.

Results

In this study, nine RNA-seq libraries of fetus, child and adult rabbits’ leg muscles were constructed. A total of 278 differentially expressed miRNAs (DEmiRNAs) were identified. In the fetus vs. child group, the main functional enrichments were involved in membrane and transport. Pathway enriched terms of up-regulated DEmiRNAs were connected with the differentiation and hypertrophy of skeletal muscle, and down-regulated ones were related to muscle structure and metabolic capacity. In the child vs. adult group, functions were associated to positioning and transportation, and pathways were relevant to ECM, muscle structure and hypertrophy. Finally, ocu-miR-185-3p and ocu-miR-370-3p, which had the most target genes, were identified as hub-miRNAs in these two groups.

Conclusions

In short, we summarized the highly expressed and uniquely expressed DEmiRNAs of fetus, child and adult rabbits’ leg muscles. Besides, the potential functional changes of miRNAs in two consecutive stages have been explored. Among them, the ocu-miR-185-3p and ocu-miR-370-3p with the most target genes were selected as hub-miRNAs. These data improved the understanding of the regulatory molecules of meat rabbit development, and provided a novel perspective for molecular breeding of meat rabbits.
Hemogram-derived ratios as prognostic markers of ICU admission in COVID-19
Authors: Velazquez Sara , Madurga Rodrigo , Castellano José María , Rodriguez-Pascual Jesús , de Aguiar Diaz Obregon Santiago Ruiz , Jimeno Sara , Montero Juan Ignacio , Wichner Paula Sol Ventura , López-Escobar Alejandro
Published: July 2021

Background

The vast impact of COVID-19 call for the identification of clinical parameter that can help predict a torpid evolution. Among these, endothelial injury has been proposed as one of the main pathophysiological mechanisms underlying the disease, promoting a hyperinflammatory and prothrombotic state leading to worse clinical outcomes. Leukocytes and platelets play a key role in inflammation and thrombogenesis, hence the objective of the current study was to study whether neutrophil-to-lymphocyte ratio (NLR), platelets-to-lymphocyte ratio (PLR), the systemic immune-inflammation index (SII) as well as the new parameter neutrophil-to-platelet ratio (NPR), could help identify patients who at risk of admission at Intensive Care Units.

Methods

A retrospective observational study was performed at HM Hospitales including electronic health records from 2245 patients admitted due to COVID-19 from March 1 to June 10, 2020. Patients were divided into two groups, admitted at ICU or not.

Results

Patients who were admitted at the ICU had significantly higher values in all hemogram-derived ratios at the moment of hospital admission compared to those who did not need ICU admission. Specifically, we found significant differences in NLR (6.9 [4–11.7] vs 4.1 [2.6–7.6], p <  0.0001), PLR (2 [1.4–3.3] vs 1.9 [1.3–2.9], p = 0.023), NPR (3 [2.1–4.2] vs 2.3 [1.6–3.2], p <  0.0001) and SII (13 [6.5–25.7] vs 9 [4.9–17.5], p <  0.0001) compared to those who did not require ICU admission. After multivariable logistic regression models, NPR was the hemogram-derived ratio with the highest predictive value of ICU admission, (OR 1.11 (95% CI: 0.98–1.22, p = 0.055).

Conclusions

Simple, hemogram-derived ratios obtained from early hemogram at hospital admission, especially the novelty NPR, have shown to be useful predictors of risk of ICU admission in patients hospitalized due to COVID-19.
Heme oxygenase-1 and neopterin plasma/serum levels and their role in diagnosing active and latent TB among HIV/TB co-infected patients: a cross sectional study
Authors: Uwimaana Esther , Bagaya Bernard S. , Castelnuovo Barbara , Kateete David P. , Godwin Anguzu , Kiwanuka Noah , Whalen Christopher C. , Joloba Moses L.
Published: July 2021

Background

Tuberculosis (TB) diagnosis in the context of HIV co-infection remains challenging. Heme oxygenase 1 (HO-1) and neopterin have been validated as potential biomarkers for TB diagnosis. Latent TB infection (LTBI) is diagnosed using tuberculin skin test (TST) and interferon gamma release assays (T-Spot and QuantiFERON TB gold tests, respectively). However, these tests have shown challenges and yet diagnosing LTBI is important for the overall control of TB. This study was conducted to determine the levels of H0–1 and neopterin, and their role in the diagnosis of TB among individuals enrolled in the Community Health and Social Network of Tuberculosis (COHSONET) study and the Kampala TB Drug Resistance Survey (KDRS).

Methods

This was a nested cross-sectional study. Plasma and serum samples collected from 140 patients at Mulago National Referral Hospital, Kampala Uganda were used. M.tb culture was performed on sputum to confirm active TB(ATB) and QuantiFERON TB gold test to confirm latent TB infection (LTBI). ELISAs were performed to determine the levels of HO-1 and neopterin. Data analysis was done using t-test and Receiver Operating Characteristic curves to determine the diagnostic accuracy.

Results

HO-1 levels among active tuberculosis (ATB)/HIV-infected patients and LTBI/HIV-infected patients were 10.7 ng/ml (IQR: 7.3–12.7 ng/ml) and 7.5 ng/ml (IQR: 5.4–14.1 ng/ml) respectively. Neopterin levels among ATB/HIV-positive patients and LTBI/HIV-positive patients were 11.7 ng/ml (IQR: 5.2.4 ng/ml) and 8.8 ng/ml (IQR: 2.4–19.8 ng/ml), respectively. HO-1 showed a sensitivity of 58.57% and a specificity of 67.14% with area under the curve (AUC) of 0.57 when used to discriminate between ATB and LTB. Neopterin showed an AUC of 0.62 with a sensitivity of 57.14% and a specificity of 60.0% when used to distinguish ATB from LTB.

Conclusion

There was no in significant difference in HO-1 concentration levels of ATB individuals compared to LTB individuals. There was a significant difference in neopterin concentrations levels of ATB individuals compared to latently infected individuals. Findings from this study, show that HO-1 and neopterin have poor ability to distinguish between ATB and LTB.
A different point of view: the evaluation of motor imagery perspectives in patients with sensorimotor impairments in a longitudinal study
Authors: Gäumann Szabina , Gerber Rahel Sarah , Suica Zorica , Wandel Jasmin , Schuster-Amft Corina
Published: July 2021

Background

Motor imagery (MI) has been successfully applied in neurological rehabilitation. Little is known about the spontaneous selection of the MI perspectives in patients with sensorimotor impairments. What perspective is selected: internal (first-person view), or external (third-person view)? The aim was to evaluate the MI perspective preference in patients with sensorimotor impairments.

Methods

In a longitudinal study including four measurement sessions, 55 patients (25 stroke, 25 multiple sclerosis, 5 Parkinson’s disease; 25 females; mean age 58 ± 14 years) were included. MI ability and perspective preference in both visual and kinaesthetic imagery modalities were assessed using the Kinaesthetic and Visual Imagery Questionnaire-20 (KVIQ-20), the body rotation task (BRT), and mental chronometry (MC). Additionally, patients’ activity level was assessed. Descriptive analyses were performed regarding different age- (< 45, 45–64, > 64), activity levels (inactive, partially active, active), and KVIQ-20 movement classifications (axial, proximal, distal, upper and lower limb). A mixed-effects model was used to investiage the relationship between the primary outcome (MI perspective: internal, external) with the explanatory variables age, MI modality (visual, kinaesthetic), movement type (axial, proximal, distal), activity levels and the different assessments (KVIQ-20, BRT, MC).

Results

Imagery modality was not a significant predictor of perspective preference. Over the four measurement sessions, patients tended to become more consistent in their perspective selection, however, time point was not a significant predictor. Movement type was a significant predictor: imagination of distal vs. axial and proximal vs. axial movements were both associated with preference for external perspective. Patients with increased physical activity level tend to use internal imagery, however, this effect was borderline not statistically significant. Age was neither a significant precictor. Regarding the MI assessments, the KVIQ- 20 score was a significant predictor. The patients with higher test scores tend to use the external perspective.

Conclusion

It is recommended to evaluate the spontaneous MI perspective selection to design patient-specific MI training interventions. Distal movements (foot, finger) may be an indicator when evaluating the consistency of the MI perspective in patients with sensorimotor impairments.
Feasibility and effectiveness of afatinib for poor performance status patients with EGFR-mutation-positive non-small-cell lung cancer: a retrospective cohort study
Authors: Wu Chiao-En , Chang Ching-Fu , Huang Chen-Yang , Yang Cheng-Ta , Kuo Chih-Hsi Scott , Hsu Ping-Chih , Chang John Wen-Cheng
Published: July 2021

Background

Afatinib is one of the standard treatments for patients with epidermal growth factor receptor (EGFR)-mutated non-small-cell lung cancer (NSCLC). However, data on the use of afatinib in patients with poor performance status (PS ≥ 2) are limited. This study aimed to retrospectively review the clinical outcomes and safety of afatinib treatment in EGFR-mutation-positive (EGFRm+) NSCLC patients with PS ≥ 2.

Methods

The data for 62 patients who were treated at Linkou Chang Gung Memorial Hospital from January 2010 to August 2019 were retrospectively reviewed. Patients’ clinicopathological features were obtained, and univariate and multivariate analyses were performed to identify possible prognostic factors. Data on adverse events were collected to evaluate general tolerance for afatinib therapy.

Results

Until February 2020, the objective response rate, disease control rate, median progression-free survival (PFS), and overall survival (OS) were 58.1% (36/62), 69.4% (43/62), 8.8 months, and 12.9 months, respectively. The absence of liver metastasis (PFS: p = 0.044; OS: p = 0.061) and good disease control (p < 0.001 for PFS and OS) were independent favorable prognostic factors for PFS and OS. Bone metastasis (p = 0.036) and dose modification (reduction/interruption, p = 0.021) were predictors of disease control.

Conclusion

Afatinib demonstrated acceptable efficacy and safety in the current cohort. This study provided evidence to support the use of afatinib as a first-line treatment in EGFRm+ NSCLC patients with poor PS.
Construction of a novel mRNA-signature prediction model for prognosis of bladder cancer based on a statistical analysis
Authors: Li Jianpeng , Cao Jinlong , Li Pan , Yao Zhiqiang , Deng Ran , Ying Lijun , Tian Junqiang
Published: July 2021

Background

Bladder cancer (BC) is a common malignancy neoplasm diagnosed in advanced stages in most cases. It is crucial to screen ideal biomarkers and construct a more accurate prognostic model than conventional clinical parameters. The aim of this research was to develop and validate an mRNA-based signature for predicting the prognosis of patients with bladder cancer.

Methods

The RNA-seq data was downloaded from the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO). Differentially expressed genes (DEGs) were screened in three datasets, and prognostic genes were identified from the training set of TCGA dataset. The common genes between DEGs and prognostic genes were narrowed down to six genes via Least Absolute Shrinkage and Selection Operator (LASSO) regression, and stepwise multivariate Cox regression. Then the gene-based risk score was calculated via Cox coefficient. Time-dependent receiver operating characteristic (ROC) and Kaplan-Meier (KM) survival analysis were used to assess the prognostic power of risk score. Multivariate Cox regression analysis was applied to construct a nomogram. Decision curve analysis (DCA), calibration curves, and time-dependent ROC were performed to assess the nomogram. Finally, functional enrichment of candidate genes was conducted to explore the potential biological pathways of candidate genes.

Results

SORBS2, GPC2, SETBP1, FGF11, APOL1, and H1–2 were screened to be correlated with the prognosis of BC patients. A nomogram was constructed based on the risk score, pathological stage, and age. Then, the calibration plots for the 1-, 3-, 5-year OS were predicted well in entire TCGA-BLCA patients. Decision curve analysis (DCA) indicated that the clinical value of the nomogram was higher than the stage model and TNM model in predicting overall survival analysis. The time-dependent ROC curves indicated that the nomogram had higher predictive accuracy than the stage model and risk score model. The AUC of nomogram time-dependent ROC was 0.763, 0.805, and 0.806 for 1-year, 3-year, and 5-year, respectively. Functional enrichment analysis of candidate genes suggested several pathways and mechanisms related to cancer.

Conclusions

In this research, we developed an mRNA-based signature that incorporated clinical prognostic parameters to predict BC patient prognosis well, which may provide a novel prognosis assessment tool for clinical practice and explore several potential novel biomarkers related to the prognosis of patients with BC.