bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparative Risk of Renal Adverse Events in Patients Receiving Immune Checkpoint Inhibitors: A Bayesian Network Meta-Analysis
Authors: Liu Kang , Qin Zhongke , Xu Xueqiang , Li Ting , Ge Yifei , Mao Huijuan , Xing Changying
Published: June 2021

Background

Immune checkpoint inhibitors (ICIs) have brought a paradigm shift to cancer treatment. However, little is known about the risk of renal adverse events (RAEs) of ICI-based regimens, especially ICI combination therapy.

Methods

We carried out a network meta-analysis of randomized controlled trials (RCTs) to compare the risk of RAEs between ICI-based regimens and traditional cancer therapy, including chemotherapy and targeted therapy. Subgroup analysis was conducted based on tumor types.

Results

Ninety-five eligible RCTs involving 40,552 participants were included. The overall incidence of RAEs, grade 3–5 RAEs, acute kidney injury (AKI), and grade 3–5 AKI was 4.3%, 1.2%, 1.3%, and 0.8%, respectively. Both ICI-based treatment regimens and traditional cancer therapy showed significantly higher risk of RAEs and AKI than the placebo. Among ICI monotherapy, anti-PD-1 (RR: 0.51, 95%CI: 0.29–0.91) was significantly safer than anti-CTLA-4 in terms of RAEs. Anti-CTLA-4 showed significantly higher toxicity than anti-PD-1 (RR: 0.33, 95%CI: 0.14-0.77), anti-PD-L1 (RR: 0.38, 95%CI:0.16-0.91), and anti-PD-1 plus anti-CTLA-4 (RR: 0.32, 95%CI: 0.12-0.87) in terms of grade 3-5 RAEs. The difference was not significant between ICI monotherapy and traditional cancer therapy, except that targeted therapy seemed the least toxic therapy in terms of the incidence of AKI. Anti-CTLA-4 plus anti-PD-1 were associated with higher risk of RAEs than anti-PD-1 (RR: 1.61, 95%CI: 1.02–2.56). The difference was not significant between other dual ICI regimens and ICI monotherapy in terms of RAEs and AKI. ICI plus chemotherapy showed increased risk of both RAEs and AKI compared with ICI monotherapy, chemotherapy, and targeted therapy. The overall results remained robust in the meta-regression and sensitivity analyses.

Conclusions

Among ICI monotherapy, anti-CTLA-4 appeared to be associated with increased toxicity, especially in terms of grade 3–5 RAEs. Anti-CTLA-4 plus anti-PD-1 were associated with higher risk of RAEs than anti-PD-1. However, the difference was not significant between other dual ICI regimens and ICI monotherapy in terms of RAEs and AKI. ICIs plus chemotherapy seemed to be the most toxic treatment regimen in terms of RAEs, AKI, and grade 3–5 AKI.

Systematic Review Registration

PROSPERO, identifier CRD42020197039.
The Angiotensin-Converting Enzyme Inhibitory State Promotes the Transformation of Non-Small Cell Lung Cancer Blood Supply Pattern Toward Vasculogenic Mimicry Formation
Authors: Xu Kandi , Han Huize , Luo Yexin , Ye Hong , Lin Hongxia , Ni Lei
Published: June 2021

Tumor microenvironment plays an important role in tumor proliferation, metastasis, and angiogenesis. Local RAS is a key factor to tumor proliferation and metastasis in NSCLC microenvironment, but its role on angiogenesis and VM formation remains unclear. Although overwhelming majority of previous studies suggested that VM is well established in aggressive tumor and facilitates tumor growth and metastasis, we put forward different views from another angle. We proved that status of tumor blood supply patterns, including VM channels and endothelial vessels, can dynamically exchange with each other along with local RAS fluctuations in microenvironment. Quantitatively, ACE2/ACEI promotes VM formation via Nodal/Notch4 activation; while structurally, ACE2/ACEI leads to a strong and solid structure of VM via inhibition of VE-cadherin internalization. These changes induced by ACE2/ACEI relate to relatively low metastasis rate and comforting prognoses of NSCLC patients.
Co-Occurring Potentially Actionable Oncogenic Drivers in Non-Small Cell Lung Cancer
Authors: Zhao Yiming , Wang Shuyuan , Yang Zhengyu , Dong Yu , Wang Yanan , Zhang Lele , Hu Hai , Han Baohui
Published: June 2021

Background

Several oncogenic drivers in non-small cell lung cancer (NSCLC) are considered actionable with available or promising targeted therapies. Although targetable drivers rarely overlap with each other, there were a minority of patients harboring co-occurring actionable oncogenic targets, whose clinical characteristics and prognosis are not yet clear.

Methods

A total of 3,077 patients with NSCLC who underwent molecular analysis by NGS were included, and their demographic and clinical data were retrospectively collected.

Results

Our study found that the frequency of NSCLC patients harboring co-occurring potentially actionable alterations was approximately 1.5% (46/3077); after excluding patients with EGFR-undetermined mutations, the incidence was 1.3% (40/3077); 80% (37/46) harbored both EGFR mutations and other potentially actionable drivers such as MET amplification (21.6%; 8/37) and alterations in ERBB2 including mutations (27%; 10/37) and amplification (21.6%; 8/37); other combinations of potentially actionable drivers including alterations in ERBB2, KRAS, MET, ALK, and RET were also identified. Additionally, de novo MET/ERBB2 amplification in patients harboring EGFR-mutant NSCLC treated with first-generation EGFR tyrosine kinase inhibitors (TKIs) was associated with shorter PFS (p < 0.05). The efficacy of TKIs in NSCLC patients harboring other co-occurring potentially actionable drivers varied across different molecular subtypes.

Conclusions

Approximately 1.5% of NSCLCs harbored co-occurring potentially actionable oncogenic drivers, commonly involving EGFR mutations. Co-occurring actionable targets may impact the efficacy of TKIs; therefore, future clinical trials in these patients should be anticipated to tailor the combination or sequential treatment strategies.
Healthcare Utilization of Complex Chronically Ill Children Managed by a Telehealth-Based Team
Authors: Braun Lindsay , Steurer Martina , Henry Duncan
Published: June 2021

Objectives: Medical advances have improved survival of critically ill children, increasing the number that have substantial ongoing care needs. The first aim of this study was to compare healthcare utilization of children with complex chronic conditions across an extensive geographic area managed by a predominantly telehealth-based team (FamiLy InteGrated Healthcare Transitions—FLIGHT) compared to matched historical controls. The second aim was to identify risk factors for healthcare utilization within the FLIGHT population.

Methods: We performed a retrospective cohort study of all patients enrolled in the care management team. First, we compared them to age- and technology-based matched historic controls across medical resource-utilization outcomes. Second, we used univariable and multivariable linear regression models to identify risk factors for resource utilization within the FLIGHT population.

Results: Sixty-four FLIGHT patients were included, with 34 able to be matched with historic controls. FLIGHT patients had significantly fewer hospital days per year (13.6 vs. 30.3 days, p = 0.02) and shorter admissions (6.0 vs. 17.3 days, p = 0.02) compared to controls. Within the telehealth managed population, increased number of technologies was associated with more admissions per year (coefficient 0.90, CI 0.05 – 1.75) and hospital days per year (16.83, CI 1.76 – 31.90), although increased number of complex chronic conditions was not associated with an increase in utilization.

Conclusion: A telehealth-based care coordination team was able to significantly decrease some metrics of healthcare utilization in a complex pediatric population. Future study is warranted into utilization of telemedicine for care coordination programs caring for children with medical complexity.
Predicting Successes and Failures of Clinical Trials With Outer Product–Based Convolutional Neural Network
Authors: Seo Sangwoo , Kim Youngmin , Han Hyo-Jeong , Son Woo Chan , Hong Zhen-Yu , Sohn Insuk , Shim Jooyong , Hwang Changha
Published: June 2021

Despite several improvements in the drug development pipeline over the past decade, drug failures due to unexpected adverse effects have rapidly increased at all stages of clinical trials. To improve the success rate of clinical trials, it is necessary to identify potential loser drug candidates that may fail at clinical trials. Therefore, we need to develop reliable models for predicting the outcomes of clinical trials of drug candidates, which have the potential to guide the drug discovery process. In this study, we propose an outer product–based convolutional neural network (OPCNN) model which integrates effectively chemical features of drugs and target-based features. The validation results via 10-fold cross-validations on the dataset used for a data-driven approach PrOCTOR proved that our OPCNN model performs quite well in terms of accuracy, F1-score, Matthews correlation coefficient (MCC), precision, recall, area under the curve (AUC) of the receiver operating characteristic, and area under the precision–recall curve (AUPRC). In particular, the proposed OPCNN model showed the best performance in terms of MCC, which is widely used in biomedicine as a performance metric and is a more reliable statistical measure. Through 10-fold cross-validation experiments, the accuracy of the OPCNN model is as high as 0.9758, F1 score is as high as 0.9868, the MCC reaches 0.8451, the precision is as high as 0.9889, the recall is as high as 0.9893, the AUC is as high as 0.9824, and the AUPRC is as high as 0.9979. The results proved that our OPCNN model shows significantly good prediction performance on outcomes of clinical trials and it can be quite helpful in early drug discovery.
Contractile Properties of MHC I and II Fibers From Highly Trained Arm and Leg Muscles of Cross-Country Skiers
Authors: Gejl Kasper Degn , Hvid Lars G. , Andersson Erik P. , Jensen Rasmus , Holmberg Hans-Christer , Ørtenblad Niels
Published: June 2021

Introduction

Little is known about potential differences in contractile properties of muscle fibers of the same type in arms and legs. Accordingly, the present study was designed to compare the force-generating capacity and Ca2+ sensitivity of fibers from arm and leg muscles of highly trained cross-country skiers.

Method

Single muscle fibers of m. vastus lateralis and m. triceps brachii of eight highly trained cross-country skiers were analyzed with respect to maximal Ca2+-activated force, specific force and Ca2+ sensitivity.

Result

The maximal Ca2+-activated force was greater for myosin heavy chain (MHC) II than MHC I fibers in both the arm (+62%, P < 0.001) and leg muscle (+77%, P < 0.001), with no differences between limbs for each MHC isoform. In addition, the specific force of MHC II fibers was higher than that of MHC I fibers in both arms (+41%, P = 0.002) and legs (+95%, P < 0.001). The specific force of MHC II fibers was the same in both limbs, whereas MHC I fibers from the m. triceps brachii were, on average, 39% stronger than fibers of the same type from the m. vastus lateralis (P = 0.003). pCa50 was not different between MHC I and II fibers in neither arms nor legs, but the MHC I fibers of m. triceps brachii demonstrated higher Ca2+ sensitivity than fibers of the same type from m. vastus lateralis (P = 0.007).

Conclusion

Comparison of muscles in limbs equally well trained revealed that MHC I fibers in the arm muscle exhibited a higher specific force-generating capacity and greater Ca2+ sensitivity than the same type of fiber in the leg, with no such difference in the case of MHC II fibers. These distinct differences in the properties of fibers of the same type in equally well-trained muscles open new perspectives in muscle physiology.
Do Extreme Climate Events Cause the Degradation of Malus sieversii Forests in China?
Authors: Shan Qianjuan , Ling Hongbo , Zhao Hangzheng , Li Mengyi , Wang Zikang , Zhang Guangpeng
Published: June 2021

Frequent extreme climate events have attracted considerable attention around the world. Malus sieversii in Xinjiang is the ancestor of cultivated apple, and it is mainly distributed in the Ili river valley at end of the Tianshan Mountains. Wild fruit forests have been degraded, but the cause remains unclear. In order to identify whether extreme climate events caused this degradation reanalysis data and atmospheric circulation indices were used to determine the trends and the reasons for extreme climate changes. Subsequently, we further investigated the effect of extreme climate events on wild fruit forest using characteristics of extreme climate indices and tree-ring chronology. We found increasing trends in both extreme precipitation and warm indices, and decreasing trends in cool indices. Extreme climate events were mainly associated with the Atlantic Multidecadal Oscillation (AMO). Analysis of data of wind and geopotential height field at 500 hPa showed that strengthening wind, increasing geopotential height, cyclone and anti-cyclone circulation drivers contributed to extreme climate events. In the non-degraded region, there were significant positive correlations between tree-ring chronology and both extreme precipitation and extreme warm indices (except for warm spell duration indicator). The other extreme indices (except for heavy rain days) had a large correlation range with tree-rings in a 4–8-year period. These results indicated that extreme precipitation and extreme warm indices intensified M. sieversii growth of the non-degraded region on multi-time scales. In contrast, the degraded region showed insignificant negative relationship between tree-ring chronology and both extreme precipitation and extreme warm indices [except for warm spell duration index (WSDI)], and significant negative correlations in a 4–8-year period were detected between tree-ring chronology and most of the extreme precipitation indices, including heavy rain days, very wet days, cold spell duration indicator, simple precipitation intensity index (SDII), and annual total precipitation. Under the long disturbance of inappropriate anthropic activities, extreme climate has caused the outbreak of pests and diseases resulting in the degeneration of wild fruit forest. Our study provides scientific guidance for the ecosystem conservation in wild fruit forest in China, and also across the region.
Transcriptomics of Differential Ripening in ‘d’Anjou’ Pear (Pyrus communis L.)
Authors: Honaas Loren , Hargarten Heidi , Hadish John , Ficklin Stephen P. , Serra Sara , Musacchi Stefano , Wafula Eric , Mattheis James , dePamphilis Claude W. , Rudell David
Published: June 2021

Estimating maturity in pome fruits is a critical task that directs virtually all postharvest supply chain decisions. This is especially important for European pear (Pyrus communis)cultivars because losses due to spoilage and senescence must be minimized while ensuring proper ripening capacity is achieved (in part by satisfying a fruit chilling requirement). Reliable methods are lacking for accurate estimation of pear fruit maturity, and because ripening is maturity dependent it makes predicting ripening capacity a challenge. In this study of the European pear cultivar ‘d’Anjou’, we sorted fruit at harvest based upon on-tree fruit position to build contrasts of maturity. Our sorting scheme showed clear contrasts of maturity between canopy positions, yet there was substantial overlap in the distribution of values for the index of absorbance difference (IAD), a non-destructive spectroscopic measurement that has been used as a proxy for pome fruit maturity. This presented an opportunity to explore a contrast of maturity that was more subtle thanIADcould differentiate, and thus guided our subsequent transcriptome analysis of tissue samples taken at harvest and during storage. Using a novel approach that tests for condition-specific differences of co-expressed genes, we discovered genes with a phased character that mirrored our sorting scheme. The expression patterns of these genes are associated with fruit quality and ripening differences across the experiment. Functional profiles of these co-expressed genes are concordant with previous findings, and also offer new clues, and thus hypotheses, about genes involved in pear fruit quality, maturity, and ripening. This work may lead to new tools for enhanced postharvest management based on activity of gene co-expression modules, rather than individual genes. Further, our results indicate that modules may have utility within specific windows of time during postharvest management of ‘d’Anjou’ pear.
Functional Characterization of VDACs in Grape and Its Putative Role in Response to Pathogen Stress
Authors: Xu Tengfei , Wang Xiaowei , Ma Hui , Su Li , Wang Wenyuan , Meng Jiangfei , Xu Yan
Published: June 2021

Voltage-dependent anion channels (VDACs) are the most abundant proteins in the mitochondrial outer membranes of all eukaryotic cells. They participate in mitochondrial energy metabolism, mitochondria-mediated apoptosis, and cell growth and reproduction. Here, the chromosomal localizations, gene structure, conserved domains, and phylogenetic relationships were analyzed. The amino acid sequences of VDACs were found to be highly conserved. The tissue-specific transcript analysis from transcriptome data and qRT-PCR demonstrated that grapevine VDACs might play an important role in plant growth and development. It was also speculated that VDAC3 might be a regulator of modulated leaf and berry development as the expression patterns during these developmental stages are up-regulated. Further, we screened the role of all grape VDACs’ response to pathogen stress and found that VDAC3 from downy mildew Plasmopara viticola-resistant Chinese wild grapevine species Vitis piasezkii “Liuba-8” had a higher expression than the downy mildew susceptible species Vitis vinifera cv. “Thompson Seedless” after inoculation with P. viticola. Overexpression of VpVDAC3 resulted in increased resistance to pathogens, which was found to prevent VpVDAC3 protein accumulation through protein post-transcriptional regulation. Taken together, these data indicate that VpVDAC3 plays a role in P. viticola defense and provides the evidence with which to understand the mechanism of grape response to pathogen stress.
Remote Sensing Phenology of Antarctic Green and Red Snow Algae Using WorldView Satellites
Authors: Gray Andrew , Krolikowski Monika , Fretwell Peter , Convey Peter , Peck Lloyd S. , Mendelova Monika , Smith Alison G. , Davey Matthew P.
Published: June 2021

Snow algae are an important group of terrestrial photosynthetic organisms in Antarctica, where they mostly grow in low lying coastal snow fields. Reliable observations of Antarctic snow algae are difficult owing to the transient nature of their blooms and the logistics involved to travel and work there. Previous studies have used Sentinel 2 satellite imagery to detect and monitor snow algal blooms remotely, but were limited by the coarse spatial resolution and difficulties detecting red blooms. Here, for the first time, we use high-resolution WorldView multispectral satellite imagery to study Antarctic snow algal blooms in detail, tracking the growth of red and green blooms throughout the summer. Our remote sensing approach was developed alongside two Antarctic field seasons, where field spectroscopy was used to build a detection model capable of estimating cell density. Global Positioning System (GPS) tagging of blooms and in situ life cycle analysis was used to validate and verify our model output. WorldView imagery was then used successfully to identify red and green snow algae on Anchorage Island (Ryder Bay, 67°S), estimating peak coverage to be 9.48 × 104 and 6.26 × 104 m2, respectively. Combined, this was greater than terrestrial vegetation area coverage for the island, measured using a normalized difference vegetation index. Green snow algae had greater cell density and average layer thickness than red blooms (6.0 × 104 vs. 4.3 × 104 cells ml−1) and so for Anchorage Island we estimated that green algae dry biomass was over three times that of red algae (567 vs. 180 kg, respectively). Because the high spatial resolution of the WorldView imagery and its ability to detect red blooms, calculated snow algal area was 17.5 times greater than estimated with Sentinel 2 imagery. This highlights a scaling problem of using coarse resolution imagery and suggests snow algal contribution to net primary productivity on Antarctica may be far greater than previously recognized.
COVID-19 Vaccination Intentions: The Theory of Planned Behavior, Optimistic Bias, and Anticipated Regret
Authors: Wolff Katharina
Published: June 2021

High vaccination rates within the general population are essential for overcoming the current COVID-19 pandemic. The aim of the present study was to investigate intentions to receive a COVID-19 vaccine as well as the predictors of such intentions. A representative sample of the Norwegian population (N = 1,003, 49.5% females, Mage = 47.9, SD = 17.1) filled in an online questionnaire assessing the components of the Theory of planned behavior (attitudes, subjective norms, and perceived behavioral control), as well as optimistic bias and anticipated regret. Results showed that a majority (61.6%) of participants intend to get vaccinated. Regression analysis revealed that intentions were predicted by positive attitudes toward vaccination (β = 0.31, p < 0.001), subjective norms in favor of vaccination in one’s family (β = 0.23, p < 0.001), perceived behavioral control (β = 0.09, p < 0.001), and by anticipated net regret (β = 0.32, p < 0.001), explaining 69% (f2 = 2.23) of the variance in intentions. Optimistic bias did not predict intentions.
The Knowledge Map of Sport and Exercise Psychology: An Integrative Perspective
Authors: Latinjak Alexander T. , Hatzigeorgiadis Antonis
Published: June 2021

The present work contains a personal perspective on what sport and exercise psychology (SEP) is today. It is a global synthesis of research about psychological aspects related to the context and practice of sport and exercise. The intended impact was to positively influence teaching SEP to students, to promote interdisciplinary research and practice, and to assist the development of SEP as an applied science by helping experts develop a more holistic view of the field. Over 650 theoretical and review articles about psychological concepts in connection to sport and exercise were read in the process of creating a conceptual model that reflects the essence of SEP and leads to a conceptualization of SEP based on research topics. The result was a knowledge map of SEP made up of four main research clusters: biopsychological descriptors, external variables, psychological skills, and applied SEP practice. In terms of interdisciplinarity, the present perspective on SEP suggests that sport and exercise can be used as a research paradigm or natural laboratory to study psychological aspects relevant to various scientific fields, and that sport and exercise can be used as a therapeutic framework in response to challenges that researchers and practitioners in these fields are typically addressing.
Dialogic Learning Environments That Enhance Instrumental Learning and Inclusion of Students With Special Needs in Secondary Education
Authors: Navarro-Mateu Diego , Gómez-Domínguez Teresa , Padrós Cuxart María , Roca-Campos Esther
Published: June 2021

Across Europe, the enrolment of students with special educational needs in regular classrooms is increasing, although it does not always mean access to high quality educational experience. In this context, inclusive education has been enhanced in most educational systems, but its successful implementation is still limited and has become a challenge in most countries, and specially in secondary education, when segregation due to learning achievement is more frequent. Educational practices that take into account the potential of promoting learning interactions within heterogeneous groups of students have already demonstrated contributing to educational inclusion of students with special needs. In this study we analyse the case of a secondary education school located in Valencian Community (Spain), which educates students with special needs along with their typically developing peers and is characterized by its inclusive ethos. The analysis focuses on three educational strategies implemented in the school and their impact on educational improvement and inclusion of the students with special needs: (1) co-teaching, (2) interactive groups, (3) dialogic literary gatherings. Qualitative data were obtained from communicative focus groups with teachers, communicative life stories with students and relatives, communicative observations of the three educational strategies and documentary analysis. The findings show significant increase in the students' instrumental learning, as well as an improvement in these students' overall inclusion in the school.
Coping With Oral Tongue Cancer and COVID-19 Infection
Authors: De Berardinis Rita , Guiddi Paolo , Ugolini Sara , Chu Francesco , Pietrobon Giacomo , Pravettoni Gabriella , Mastrilli Fabrizio , Chiocca Susanna , Ansarin Mohssen , Tagliabue Marta
Published: June 2021

To date, April 19, 2021, the coronavirus disease 2019 (COVID-19) caused about 140,886,773 confirmed cases and more than 3,000,000 deaths worldwide since the beginning of the pandemic. Oncology patients are usually frail due to the fear of prognosis, recurrence, and outcomes of treatments. Thus, coping with cancer is a complicated process that is necessary to overcome oncological challenge, even more in case of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) disease. This is a brief case report on a middle-aged man affected by advanced oral tongue cancer and COVID-19, describing his experience of cancer diagnosis, surgical treatment, and rehabilitation during the hospital quarantine for COVID-19. Besides the traumatic experience due to the functional alteration in breathing, eating, and speaking caused by major surgery and the concurrent facial disfigurement, our patient had to face a COVID-19 diagnosis, which implied hospital and social isolation. The aim of this perspective work is to focus on the role of the psychological support in the management of hospital distress related to COVID-19 psychophysical loneliness or alienation. In our experience, such support should anticipate patients' oncological surgery or treatment and should be implemented through telemedicine in case of isolation or after hospital discharge.
The Relationship Between Decisional Regret and Well-Being in Patients With and Without Depressive Disorders: Mediating Role of Shared Decision-Making
Authors: Xu Richard Huan , Zhou Ling-ming , Wang Dong
Published: June 2021

Background: The objectives of this study were two-fold: (1) to assess the relationship between patients' decisional regret and their well-being and (2) to examine the mediated effect of shared decision-making (SDM) on this relationship.

Methods: A cross-sectional survey was conducted in five cities in Southern China. Patients were asked to fill out questionnaires assessing their decisional regret, SDM, subjective well-being, and depressive status. Mediation analysis was used to investigate the effect of SDM on the relationship between patients' decisional regret and their subjective well-being.

Results: The findings showed significant direct negative effects of decisional regret on subjective well-being and SDM. For non-depressive patients, SDM exerted a significant and indirect effect on reducing the negative influence of decisional regret on subjective well-being.

Conclusions: Findings suggest that implementation of SDM can decrease patients' decisional regret and improve their well-being; however, there is a need to examine their depressive status as part of routine healthcare.
Prevalence and Risk Factors of Anxiety and Depression in Rosacea Patients: A Cross-Sectional Study in China
Authors: Chen Mengting , Deng Zhili , Huang Yingxue , Li Ji
Published: June 2021

Rosacea is a chronic inflammatory skin disease characterized by facial redness and bothersome symptoms. It can exert significant psychological effects and impair the quality of life of patients. To investigate the prevalence and risk predictors of anxiety and depression in rosacea patients, we conducted a cross-sectional study in an outpatient setting. Consecutive patients completed a questionnaire, which included questions on sociodemographic information and severity of signs and symptoms; they also completed the Patient Health Questionnaire and the Generalized Anxiety Disorder scale. Disease burden was assessed using Dermatology Life Quality Index (DLQI), Willing-to-Pay, and Time trade-off. Multivariate analysis was conducted to determine the risk factors for anxiety and depression. A total of 774 patients completed the survey. The prevalence of anxiety was 53.9% (95% CI: 50.4–57.4%) and that of depression was 58.1% (95% CI: 54.7–61.6%). The factors associated with anxiety were age, gender, the need to make appearances at work, severity of self-reported symptoms, the number of rosacea signs and adaptive behaviors, and disease burden. Depression was associated with younger age, more severe self-reported symptoms, more adaptive behaviors, and higher disease burden. After adjusting for demographics, the risk of anxiety or depression increased in young patients who had severe self-reported symptoms, high DLQI scores, and many adaptive behaviors. Taken together, there is a high prevalence of anxiety and depression among Chinese rosacea patients. Younger rosacea patients who have more severe self-reported symptoms and higher disease burden are prone to anxiety and depression.
Coding Public Health Interventions for Health Technology Assessments: A Pilot Experience With WHO's International Classification of Health Interventions (ICHI)
Authors: Wübbeler Markus , Geis Sebastian , Stojanovic Jovana , Elliott Lise , Gutierrez-Ibarluzea Iñaki , Lenoir-Wijnkoop Irene
Published: June 2021

Introduction: An important requirement for successful public health interventions is a standardized classification in order to make these health technologies comparable in all contexts and recognized by all parties. The WHO International Classification of Health Interventions (ICHI), including an integrated public health component, has been developed to propose such an international standard.

Methods: To test (a) the translation of public health interventions to ICHI codes and (b) the technical handling and general coding in public health, we used a set of public health interventions from a recent cross-sectional survey among Health Technology Assessment professionals.

Results: Our study showed that handling of the ICHI interface is stable, that there is a need for specificity and adequate detail of intervention descriptions and desired outcomes to code adequately with ICHI and that the professional background of the coder, as well as his/her sex might influence the selection of codes.

Conclusion: International Classification of Health Interventions provides a good coverage of public health interventions. However, the broader character of system wide interventions, often involving a variety of institutions and stakeholders, may present a challenge to the application of ICHI coding. Based on this experience, we would tailor future surveys more specifically to the needs of the classification and we advise training for health professionals before coding with ICHI. Standards of reporting will likely strengthen insights about the efficiency of primary prevention interventions and thus benefit long-term health of populations and structured HTA reporting process.
HearMeVirtual Reality: Using Virtual Reality to Facilitate Empathy Between Hearing Impaired Children and Their Parents
Authors: Embøl Lasse , Hutters Carl , Junker Andreas , Reipur Daniel , Adjorlu Ali , Nordahl Rolf , Serafin Stefania
Published: June 2021

Cochlear implants (CI) enable hearing in individuals with sensorineural hearing loss, albeit with difficulties in speech perception and sound localization. In noisy environments, these difficulties are disproportionately greater for CI users than for children with no reported hearing loss. Parents of children with CIs are motivated to experience what CIs sound like, but options to do so are limited. This study proposes using virtual reality to simulate having CIs in a school setting with two contrasting settings: a noisy playground and a quiet classroom. To investigate differences between hearing conditions, an evaluation utilized a between-subjects design with 15 parents (10 female, 5 male; age M = 38.5, SD = 6.6) of children with CIs with no reported hearing loss. In the virtual environment, a word recognition and sound localization test using an open-set speech corpus compared differences between simulated unilateral CI, simulated bilateral CI, and normal hearing conditions in both settings. Results of both tests indicate that noise influences word recognition more than it influences sound localization, but ultimately affects both. Furthermore, bilateral CIs are equally to or significantly beneficial over having a simulated unilateral CI in both tests. A follow-up qualitative evaluation showed that the simulation enabled users to achieve a better understanding of what it means to be an hearing impaired child.
Prognostic Nomogram of Prognosis-Related Genes and Clinicopathological Characteristics to Predict the 5-Year Survival Rate of Colon Cancer Patients
Authors: Huang Chao , Zhao Jiefeng , Zhu Zhengming
Published: June 2021

Background: The Cancer Genome Atlas (TCGA) has established a genome-wide gene expression profile, increasing our understanding of the impact of tumor heredity on clinical outcomes. The aim of this study was to construct a nomogram using data from the TCGA regarding prognosis-related genes and clinicopathological characteristics to predict the 5-years survival rate of colon cancer (CC) patients.

Methods: Kaplan–Meier and Cox regression analyses were used to identify genes associated with the 5-years survival rate of CC patients. Cox regression was used to analyze the relationship between the clinicopathological features and prognostic genes and overall survival rates in patients with CC and to identify independent risk factors for the prognosis of CC patients. A nomogram for predicting the 5-years survival rate of CC patients was constructed by R software.

Results: A total of eight genes (KCNJ14, CILP2, ATP6V1G2, GABRD, RIMKLB, SIX2, PLEKHA8P1, and MPP2) related to the 5-years survival of rate CC patients were identified. Age, stage, and PLEKHA8P1 were independent risk factors for the 5-years survival rate in patients with CC. The accuracy, sensitivity and specificity of the nomogram model constructed by age, TNM staging, and PLEKHA8P1 for predicting the 5-years survival of rate CC patients were 83.3, 83.97, and 85.79%, respectively.

Conclusion: The nomogram can correctly predict the 5-year survival rate of patients with CC, thus aiding the individualized decision-making process for patients with CC.
Estimating the Economic Impact and Assessing Owners' Knowledge and Practices of Epizootic Lymphangitis in Equine Cart Animals in Central and South Gondar Zones, Amhara Region, Ethiopia
Authors: Molla Amsalu Misgie , Fentahun Tewodros , Jemberu Wudu T.
Published: June 2021

Epizootic lymphangitis (EL) is a chronic, contagious, fungal disease of equids. The disease is highly prevalent in cart pulling equines of Ethiopia affecting the livelihood of the cart owning households and welfare of the cart animals. This study estimated the economic impacts of EL and assessed cart owners' knowledge and practices related to the disease in northwest Ethiopia. A multistage cluster sampling approach was implemented to select cart animal owners for the study. A total of 274 cart animal owners were interviewed to collect data for the study. The average annual economic loss per cart owner was estimated at Ethiopian Birr (ETB) 8447. Of this loss, the ETB 4364, 2838, and 1245 were due to mortality, working power loss, and treatment costs, respectively. When the loss was computed only for affected car owners, it was on average ETB 9835 per affected cart owner. The average annual animal level loss was estimated at ETB 6587 per cart animal. Mortality was the largest contributor of the overall economic losses. There was a statistically significant difference in average economic losses per household between study towns (P < 0.05). The knowledge and practice study revealed that 51.2% of the respondents had good knowledge level (knowledge score above the mean score) of EL, but only 45.2% of the respondents had a good practice related to EL. A multivariable logistic regression analysis revealed that socio-demographic factors such as educational level and town of residence were significantly associated with EL knowledge level of the respondents (P < 0.05), and on the other hand, knowledge level and residence of the respondents were significantly associated with EL practice level (P < 0.05). The study generally indicates that EL causes significant economic impact on the cart business, but cart owners had insufficient knowledge and poor control and preventive practices to combat the disease. Attention should be accorded to control the disease and reduce its impact on the livelihood of cart owners. As part of the control measure, more awareness creation about the disease and its preventive and management measures for cart owners will very important.
Non-antibiotic compounds affecting the growth of urinary pathogens during urine culture: a preliminary in vitro study
Authors: Gajdács Márió
Published: June 2021

Introduction: Urine samples are one of the most frequently submitted samples for culture to clinical microbiology laboratories, exceeding the number of most of the other clinical sample types. Various non-antibiotic pharmaceutical compounds may have inhibitory properties on bacteria, as many of these agents accumlate in/eliminated through urine. Methods: Sixty (n=60) pharmacological agents were tested during our experiments. Bacillus subtilis ATCC 6633, Escherichia coli ATCC 25922, Klebsiella pneumoniae ATCC 700603 (ESBL-producing) and Staphylococcus aureus ATCC 29213 were the bacterial strains utilized in this study. Detection of inhibitory activity among the tested compounds was performed on Mueller-Hinton plates, using disk diffusion method. Results: Nineteen (n=19) compounds presented with various levels of inhibitory activity on the tested bacterial strains (four compounds for K. pneumoniae, seven compounds on E. coli and sixteen compounds on S. aureus). The compounds showed the highest levels of inhibitory activity on B. subtilis ATCC 6633, which is one of the main bacterial strains used for the screening of the ’intrinsic’ antibacterial activity of urine. Conclusion: Our results suggest that further experiments, involving additional pharmacological agents is warranted, to establish the full extent of their influence on the appropriate culture of urine samples.
Modelled Quantification of Different Sources of Nitrogen Inefficiency in Semi-Arid Cropping Systems
Authors: Nasrollahi Niloufar , Hunt James , Tang Caixian , Cann David
Published: June 2021

Most dryland grain growers in Australia retain all or most of their crop residues to protect the soil from erosion and to improve water conservation but retaining stubbles with a high carbon-to-nitrogen (C:N) ratio can affect N availability to crops. A simulation experiment was conducted to investigate the effects of N fertilizer application rate and residue retention on soil N dynamics. The simulation used seven N fertilizer application rates (0, 25, 50, 75, 100, 150 and 200 kg N ha−1) to wheat (Triticum aestivum) over 27 years (1990–2016) at four locations across a gradient in annual rainfall in Victoria, Australia. Nitrogen immobilization, denitrification and N leaching loss were predicted and collectively defined as sources of N inefficiency. When residues were retained, immobilization was predicted to be the biggest source of inefficiency at all simulated sites at N application rates currently used by growers. Leaching became a bigger source of inefficiency at one site with low soil water-holding capacity, but only at N rates much higher than would currently be commercially applied, resulting in high levels of nitrate (NO3−) accumulating in the soil. Denitrification was an appreciable source of inefficiency at higher rainfall sites. Further research is necessary to evaluate strategies to minimize immobilization of N in semi-arid cropping systems.
Does Increasing Model Resolution Improve the Real-Time Forecasts of Western North Pacific Tropical Cyclones?
Authors: Moon Jihong , Park Jinyoung , Cha Dong-Hyun
Published: June 2021

In this study, the general impact of high-resolution moving nesting domains on tropical cyclone (TC) intensity and track forecasts was verified, for a total of 107 forecast cases of 33 TCs, using the Weather Research and Forecasting (WRF) model. The experiment, with a coarse resolution of 12 km, could not significantly capture the intensification process, especially for maximum intensities (>60 m s−1). The intense TCs were better predicted by experiments using a moving nesting domain with a horizontal resolution of 4 km. The forecast errors for maximum wind speed and minimum sea-level pressure decreased in the experiment with higher resolution; the forecast of lifetime maximum intensity was improved. For the track forecast, the experiment with a coarser resolution tended to simulate TC tracks deviating rightward to the TC motions in the best-track data; this erroneous deflection was reduced in the experiment with a higher resolution. In particular, the track forecast in the experiment with a higher resolution improved more frequently for intense TCs that were generally distributed at relatively lower latitudes among the test cases. The sensitivity of the track forecast to the model resolution was relatively significant for lower-latitude TCs. On the other hand, the track forecasts of TCs moving to the mid-latitudes, which were primarily influenced by large-scale features, were not sensitive to the resolution.
Understanding the Major Impact of Planetary Boundary Layer Schemes on Simulation of Vertical Wind Structure
Authors: Zhang Lei , Xin Jinyuan , Yin Yan , Chang Wenyuan , Xue Min , Jia Danjie , Ma Yongjing
Published: June 2021

The structure and evolution of the atmospheric planetary boundary layer (PBL) plays an important role in the physical and chemical processes of cloud–radiation interaction, vertical mixing and pollutant transport in the atmosphere. The PBL parameterization scheme describes the vertical transport of atmospheric momentum, heat, water vapor and other physical quantities in the boundary layer. The accuracy of wind field simulation and prediction is one of the most significant parameters in the field of atmospheric science and wind energy. Limited by the observation data, there are few studies on wind energy development. A 3D Doppler wind LiDAR (DWL) providing the high-vertical-resolution wind data over the urban complex underlying surface in February 2018 was employed to systematically evaluate the accuracy of vertical wind field simulation for the first time. 11 PBL schemes of the Weather Research and Forecasting Model (WRF) were employed in simulation. The model results were evaluated in groups separated by weather (sunny days, hazy days and windy days), observation height layers of wind field, and various observation wind speeds. Among these factors, the simulation accuracy is most closely related to the observation height layers of wind field. The simulation is fairly accurate at a height of 1000–2000 m, as most of the relative mean biases for wind speed and wind direction are less than 20% and 6% respectively. Below 1000 m, the wind speed and direction biases are about 30–150% m·s−1 and 6–30%, respectively. Moreover, when the observed wind speed was lower than 5 m·s−1, the biases were usually large, and the wind speed relative mean bias reaches up to 50–300%. In addition, the accuracy of the simulated wind profile is better in the range of 10–15 m·s−1 than other speed ranges, and is better above 1000 m than below 1000 m in the boundary layer. We see that the WRF boundary layer schemes have different applicabilities to different weather conditions. The WRF boundary layer schemes have significant differences in wind field simulations, with larger error under the complex topographies. A PBL scheme is not likely to maintain its advantages in the long term under different conditions including altitude and weather conditions.
Overview of Evidence-Based Chemotherapy for Oral Cancer: Focus on Drug Resistance Related to the Epithelial-Mesenchymal Transition
Authors: Sha Jingjing , Bai Yunpeng , Ngo Huy Xuan , Okui Tatsuo , Kanno Takahiro
Published: June 2021

The increasing incidence of resistance to chemotherapeutic agents has become a major issue in the treatment of oral cancer (OC). Epithelial-mesenchymal transition (EMT) has attracted a great deal of attention in recent years with regard to its relation to the mechanism of chemotherapy drug resistance. EMT-activating transcription factors (EMT-ATFs), such as Snail, TWIST, and ZEB, can activate several different molecular pathways, e.g., PI3K/AKT, NF-κB, and TGF-β. In contrast, the activated oncological signal pathways provide reciprocal feedback that affects the expression of EMT-ATFs, resulting in a peritumoral extracellular environment conducive to cancer cell survival and evasion of the immune system, leading to resistance to multiple chemotherapeutic agents. We present an overview of evidence-based chemotherapy for OC treatment based on the National Comprehensive Cancer Network (NCCN) Chemotherapy Order Templates. We focus on the molecular pathways involved in drug resistance related to the EMT and highlight the signal pathways and transcription factors that may be important for EMT-regulated drug resistance. Rapid progress in antitumor regimens, together with the application of powerful techniques such as high-throughput screening and microRNA technology, will facilitate the development of therapeutic strategies to augment chemotherapy.
Chalcone Derivatives: Role in Anticancer Therapy
Authors: Ouyang Yang , Li Juanjuan , Chen Xinyue , Fu Xiaoyu , Sun Si , Wu Qi
Published: June 2021

Chalcones (1,3-diaryl-2-propen-1-ones) are precursors for flavonoids and isoflavonoids, which are common simple chemical scaffolds found in many naturally occurring compounds. Many chalcone derivatives were also prepared due to their convenient synthesis. Chalcones as weandhetic analogues have attracted much interest due to their broad biological activities with clinical potentials against various diseases, particularly for antitumor activity. The chalcone family has demonstrated potential in vitro and in vivo activity against cancers via multiple mechanisms, including cell cycle disruption, autophagy regulation, apoptosis induction, and immunomodulatory and inflammatory mediators. It represents a promising strategy to develop chalcones as novel anticancer agents. In addition, the combination of chalcones and other therapies is expected to be an effective way to improve anticancer therapeutic efficacy. However, despite the encouraging results for their response to cancers observed in clinical studies, a full description of toxicity is required for their clinical use as safe drugs for the treatment of cancer. In this review, we will summarize the recent advances of the chalcone family as potential anticancer agents and the mechanisms of action. Besides, future applications and scope of the chalcone family toward the treatment and prevention of cancer are brought out.