bluuebunny/crossref_metadata_2025 huggingface dataset:
Microbial-Assisted Wheat Iron Biofortification Using Endophytic Bacillus altitudinis WR10
Authors: Sun Zhongke , Yue Zonghao , Liu Hongzhan , Ma Keshi , Li Chengwei
Published: August 2021

Microbial-assisted biofortification attracted much attention recently due to its sustainable and eco-friendly nature for improving nutrient content in wheat. An endophytic strain Bacillus altitudinis WR10, which showed sophistical regulation of iron (Fe) homeostasis in wheat seedlings, inspired us to test its potential for enhancing Fe biofortification in wheat grain. In this study, assays in vitro indicated that WR10 has versatile plant growth-promoting (PGP) traits and bioinformatic analysis predicted its non-pathogenicity. Two inoculation methods, namely, seed soaking and soil spraying, with 107 cfu/ml WR10 cells were applied once before sowing of wheat (Triticum aestivum L. cv. Zhoumai 36) in the field. After wheat maturation, evaluation of yield and nutrients showed a significant increase in the mean number of kernels per spike (KPS) and the content of total nitrogen (N), potassium (K), and Fe in grains. At the grain filling stage, the abundance of Bacillus spp. and the content of N, K, and Fe in the root, the stem, and the leaf were also increased in nearly all tissues, except Fe in the stem and the leaf. Further correlation analysis revealed a positive relationship between the total abundance of Bacillus spp. and the content of N, K, and Fe in grains. Seed staining confirmed the enhanced accumulation of Fe, especially in the embryo and the endosperm. Finally, using a hydroponic coculture model, qPCR quantification indicated effective colonization, internalization, translocation, and replication of strain WR10 in wheat within 48 h. Collectively, strain WR10 assisted successful Fe biofortification in wheat in the field, laying a foundation for further large-scale investigation of its applicability and effectiveness.
Racial and Ethnic Disparities in Pain Management of Children With Limb Fractures or Suspected Appendicitis: A Retrospective Cross-Sectional Study
Authors: Guedj Romain , Marini Maddalena , Kossowsky Joe , Berde Charles B. , Kimia Amir A. , Fleegler Eric W.
Published: August 2021

Objective: To evaluate whether racial/ethnical differences in analgesia administration existed in two different cohorts of children with painful conditions: children with either limb fracture or suspected appendicitis.

Methods: Retrospective cross-sectional analysis of children visiting a pediatric emergency department (Boston Children Hospital) for limb fracture or suspected appendicitis from 2011 to 2015. We computed the proportion of children that received any analgesic treatment and any opioid analgesia. We performed multivariable logistic regressions to investigate race/ethnicity differences in analgesic and opioid administration, after adjusting for pain score, demographics and visit covariates.

Results: Among the 8,347 children with a limb fracture and the 4,780 with suspected appendicitis, 65.0 and 60.9% received any analgesic treatment, and 35.9 and 33.4% an opioid analgesia, respectively. Compared to White non-Hispanic Children, Black non-Hispanic children and Hispanic children were less likely to receive opioid analgesia in both the limb fracture cohort [Black: aOR = 0.61 (95% CI, 0.50–0.75); Hispanic aOR = 0.66 (95% CI, 0.55–0.80)] and in the suspected appendicitis cohort [Black: aOR = 0.75 (95% CI, 0.58–0.96); Hispanic aOR = 0.78 (95% CI, 0.63–0.96)]. In the limb fracture cohort, Black non-Hispanic children and Hispanic children were more likely to receive any analgesic treatment (non-opioid or opioid) than White non-Hispanic children [Black: aOR = 1.63 (95% CI, 1.33–2.01); Hispanic aOR = 1.43 (95% CI, 1.19–1.72)].

Conclusion: Racial and ethnic disparities exist in the pain management of two different painful conditions, which suggests true inequities in health care delivery. To provide equitable analgesic care, emergency departments should monitor variation in analgesic management and develop appropriate universal interventions.
Distance to Healthy Metabolic and Cardiovascular Dynamics From Fetal Heart Rate Scale-Dependent Features in Pregnant Sheep Model of Human Labor Predicts the Evolution of Acidemia and Cardiovascular Decompensation
Authors: Roux Stephane G. , Garnier Nicolas B. , Abry Patrice , Gold Nathan , Frasch Martin G.
Published: August 2021

The overarching goal of the present work is to contribute to the understanding of the relations between fetal heart rate (FHR) temporal dynamics and the well-being of the fetus, notably in terms of predicting the evolution of lactate, pH and cardiovascular decompensation (CVD). It makes uses of an established animal model of human labor, where 14 near-term ovine fetuses subjected to umbilical cord occlusions (UCO) were instrumented to permit regular intermittent measurements of metabolites lactate and base excess, pH, and continuous recording of electrocardiogram (ECG) and systemic arterial blood pressure (to identify CVD) during UCO. ECG-derived FHR was digitized at the sampling rate of 1,000 Hz and resampled to 4 Hz, as used in clinical routine. We focused on four FHR variability features which are tunable to temporal scales of FHR dynamics, robustly computable from FHR sampled at 4 Hz and within short-time sliding windows, hence permitting a time-dependent, or local, analysis of FHR which helps dealing with signal noise. Results show the sensitivity of the proposed features for early detection of CVD, correlation to metabolites and pH, useful for early acidosis detection and the importance of coarse time scales (2.5–8 s) which are not disturbed by the low FHR sampling rate. Further, we introduce the performance of an individualized self-referencing metric of the distance to healthy state, based on a combination of the four features. We demonstrate that this novel metric, applied to clinically available FHR temporal dynamics alone, accurately predicts the time occurrence of CVD which heralds a clinically significant degradation of the fetal health reserve to tolerate the trial of labor.
The U-Shaped Association Between Serum Uric Acid and Red Blood Cell Distribution Width in Acute Ischemic Stroke
Authors: Rong Ning , Zhao Pei , Yang Jin , Fan Qing-Lei , Zhang Qiang , Han Zhi-Gang , Cai Jian , Zhu De-Sheng
Published: August 2021

Objective: The U-shaped association between serum uric acid (SUA) and the functional outcome has been found in acute ischemic stroke (AIS). However, it is unclear if SUA is associated with red blood cell morphology in AIS. This study aimed to determine the relationship between SUA and red blood cell distribution width (RDW) in patients with AIS.

Methods: A cross-sectional study including 438 consecutive patients with AIS was conducted. SUA and RDW, biochemical parameters that reflect the heterogeneity of red blood cell volume, were evaluated on admission. We evaluated the association between SUA and RDW through linear curve fitting analyses and two-piecewise regression analyses.

Results: The association between SUA levels and RDW followed a U-shape in all patients. In females, the values of RDW significantly decreased with the increment of SUA (per mg/dl: β, −1.45; 95% CI: −2.15 to −0.75; p < 0.001) in patients with SUA <3.86 mg/dl and increased with the increment of SUA (per mg/dl: β, 0.60; 95% CI: 0.22–0.97; p = 0.002) in patients with SUA ≥ 3.86 mg/dl. Similar results were observed in males with the turning point of SUA = 4.82 mg/dl. After adjusting for potential confounders, a U-shaped association between SUA and RDW was maintained in females, but no statistical significance was maintained in patients with SUA ≥ 4.82 mg/dl in males (p = 0.206).

Conclusion: In the sample of patients with AIS, we found a U-shaped relationship between SUA levels and RDW, with the turning point of SUA (3.96 mg/dl in females and 4.82 mg/dl in males) by the threshold effect analysis.
Blood Flow and Shear Stress Allow Monitoring of Progression and Prognosis of Tumor Diseases
Authors: Barral Matthias , El-Sanharawi Imane , Dohan Anthony , Sebuhyan Maxime , Guedon Alexis , Delarue Audrey , Boutigny Alexandre , Mohamedi Nassim , Magnan Benjamin , Kemel Salim , Ketfi Chahinez , Kubis Nathalie , Bisdorff-Bresson Annouk , Pocard Marc , Bonnin Philippe
Published: August 2021

In the presence of tumor angiogenesis, blood flow must increase, leading to an elevation of blood flow velocities (BFVels) and wall shear stress (WSS) in upstream native arteries. An adaptive arterial remodeling is stimulated, whose purpose lies in the enlargement of the arterial inner diameter, aiming for normalization of BFVels and WSS. Remodeling engages delayed processes that are efficient only several weeks/months after initiation, independent from those governing expansion of the neovascular network. Therefore, during tumor expansion, there is a time interval during which elevation of BFVels and WSS could reflect disease progression. Conversely, during the period of stability, BFVels and WSS drop back to normal values due to the achievement of remodeling processes. Ovarian peritoneal carcinomatosis (OPC), pseudomyxoma peritonei (PMP), and superficial arteriovenous malformations (AVMs) are diseases characterized by the development of abnormal vascular networks developed on native ones. In OPC and PMP, preoperative blood flow in the superior mesenteric artery (SMA) correlated with the per-operative peritoneal carcinomatosis index (OPC: n = 21, R = 0.79, p < 0.0001, PMP: n = 66, R = 0.63, p < 0.0001). Moreover, 1 year after surgery, WSS in the SMA helped in distinguishing patients with PMP from those without disease progression [ROC-curve analysis, AUC = 0.978 (0.902–0.999), p < 0.0001, sensitivity: 100.0%, specificity: 93.5%, cutoff: 12.1 dynes/cm2]. Similarly, WSS in the ipsilateral afferent arteries close to the lesion distinguished stable from progressive AVM [ROC-curve analysis, AUC: 0.988, (0.919–1.000), p < 0.0001, sensitivity: 93.5%, specificity: 95.7%; cutoff: 26.5 dynes/cm2]. Blood flow volume is indicative of the tumor burden in OPC and PMP, and WSS represents an early sensitive and specific vascular marker of disease progression in PMP and AVM.
Linking Psychological Capital and Behavioral Support for Change: The Roles of Openness to Change and Climate for Innovation
Authors: Liu Jieqiong
Published: August 2021

Employees’ behavioral support for change is seen as a key factor for the success of organizational changes. Given the assumed importance, the study developed a multilevel conditional mediation model and examined whether psychological capital influences behavioral support for change and if so, how the effect occurs. Results from a sample of 69 team leaders and 319 followers showed that the positive impact of psychological capital on openness to change was stronger in teams high in climate for innovation and that the mediating role played by openness to change in the relationship of psychological capital to behavioral support for change was significant when climate for innovation was high.
Using Visual Representations to Demonstrate Complexity in Mixed Emotional Development Across Childhood
Authors: Fotheringham Francesca , Herman Matthias , Robbins Erin , Dritschel Barbara
Published: August 2021

Previous studies have shown a developmental trend in mixed emotional understanding. As children develop throughout childhood, they begin to recognise simultaneity of positive and negative emotions. However, previous studies have limited ecological validity as they assessed emotion choice using only a single positive and single negative emotion. Therefore, the present study aims to broaden the understanding of mixed emotional development by allowing a wider emotion choice. Mixed emotions were measured using the analogue emotions scale (AES) which allows both intensity of the emotional responses and time to be captured. In the present study, 211 children aged 4–10 were divided into one of three protagonist conditions (self, peer and adult) and read a vignette about the protagonist moving house. Choosing from seven emotions (happy, calm, surprise, sad, worry, fear and anger), they plotted the intensity and duration of each emotion they thought was represented in the vignette. The present study replicated the developmental trend that younger children are more likely than older children to choose a single emotion, and older children are more likely to perceive more simultaneity of emotion than younger children. This trend was demonstrated in the number of emotions chosen, and also the complexity of the AES pattern plotted. Additionally, the present study extended previous research by demonstrating that by broadening the emotion choice, the emotion interaction is more complex than previous studies were able to show.
Adolescents With Autism Spectrum Disorder and Anorexia Nervosa Comorbidity: Common Features and Treatment Possibilities With Cognitive Remediation Therapy and Oxytocin
Authors: Plemeniti Tololeski Barbara , Suhodolčan Grabner Ana , Kumperscak Hojka Gregoric
Published: August 2021

Autistic traits or autism spectrum disorder (ASD) can be found in 4% to 52% of anorexic patients, which makes the treatment of these patients very challenging. In this review, possible ways to treat ASD and anorexia nervosa (AN) comorbidity in children and adolescents are summarized. Over recent years, the focus has shifted from searching for the evidence of connections between these two disorders, which have started with Gillberg's study in 1983, to searching for more effective and holistic treatment of this comorbidity. The latter is known to contribute to more severe courses and worse prognosis, which is probably related to the obstacles in both diagnosing and treating. Since AN usually starts in early adolescence and high-functioning ASD children seem to begin struggling with increased pressure in adolescence, while various comorbidities can occur, it is important to improve the treatment of this comorbidity in young patients and to tailor it specifically in terms of diagnosing. In this paper, a literature review is conducted on common features and promising treatment possibilities. We describe cognitive remediation therapy and the promising pharmacotherapeutic candidate oxytocin with a special focus on adolescents.
Diagnosis and Assessment of Apathy in Elderly Chinese Patients With Cerebral Small Vessel Disease
Authors: Zhào Hóngyi , Liu Yu , Xia Zhenxi , Xie Hongyang , Huang Yonghua
Published: August 2021

Objective: The study aimed to estimate the frequency of apathy in Chinese patients with cerebral small vessel disease (CSVD) and investigate the relationship between apathy and neuroimaging markers of CSVD.

Methods: A total of 150 CSVD aged patients were recruited for a cross-sectional observational study. Following the new revised version of diagnostic criteria for apathy (DCA), each patient was evaluated successively by the neuropsychiatric inventory (NPI-apathy), geriatric depression scale (GDS), and caregiver burden scale (CBS). The MRI presence of lacunes, white matter hyperintensities, cerebral microbleeds, and perivascular spaces were rated independently. Furthermore, presence of all these MRI markers were summed in a score of 0–4 representing all CSVD features combined.

Results: According to the DCA, we found that the frequency of apathy in Chinese Alzheimer's disease patients reached 37.33%, with lack of and diminished goal-directed activities in the dimension of behavior/cognition. We did not find a close relationship between apathy and depression. Caregiver burden was positively correlated with apathy severity. Apathy, but not depression, was positively associated with total CSVD burden, rather than a separate MRI marker of CSVD.

Conclusion: As a key component of neuropsychiatric symptoms, apathy was common in Chinese elderly with CSVD, more attention should be paid to apathy in clinical practice of CSVD.
Suicidality and Its Associated Factors Among Students in Rural China During COVID-19 Pandemic: A Comparative Study of Left-Behind and Non-Left-Behind Children
Authors: Hou Tianya , Mao Xiaofei , Shao Xiaoqin , Liu Fen , Dong Wei , Cai Wenpeng
Published: August 2021

Introduction: The coronavirus disease 2019 (COVID-19) has rapidly spread worldwide. The harmful impact of COVID-19 is beyond just physical health concern. The unprecedented public health crisis has also taken its toll on the mental health of adolescents. The present study aims to estimate the prevalence of suicidal ideation and attempts and investigate the similarities and differences in the influential factors for suicidal ideation and attempts among left-behind children (LBC) and non-left-behind children (NLBC) in rural China during the COVID-19 pandemic.

Method: A total of 761 rural Chinese students, of whom 468 were left behind, completed the cross-sectional questionnaires including demographic data, Cognitive Emotion Regulation Questionnaire, nine-item Patient Health Questionnaire, seven-item Generalized Anxiety Disorder Scale, suicidal ideation, and suicidal attempts. Chi-square test, independent-sample t-test, and logistic regression were performed in the statistical analysis.

Results: Overall, 36.4 and 10.4% of rural Chinese students reported suicidal ideation (37.8% for LBC vs. 34.1% for NLBC) and attempts (11.3% for LBC vs. 8.9% for NLBC) during the COVID-19 pandemic. Among LBC, parental educational level (adjusted odds ratio, Adj. OR = 1.60), maladaptive strategies (Adj. OR = 1.04), anxious symptoms (Adj. OR = 2.61), and depressive symptoms (Adj. OR = 3.85) were significantly associated with suicidal ideation, while age (Adj. OR = 0.56), maladaptive strategies (Adj. OR = 1.08), symptoms of anxiety (Adj. OR = 3.85), and symptoms of depression (Adj. OR = 2.68) were significantly related to suicidal attempts during the COVID-19 outbreak. Among NLBC, gender (Adj. OR = 2.20), parental educational level (Adj. OR = 1.77), perceived family economic status (Adj. OR = 0.39), anxious symptoms (Adj. OR = 2.38), and depressive symptoms (Adj. OR = 2.77) were significantly associated with suicidal ideation, whereas only anxious symptom (Adj. OR = 5.85) was significantly related to suicidal attempts.

Conclusion: Suicidal ideation and attempts are prevalent among students in rural China during the COVID-19 outbreak. Our findings also revealed the shared and unique factors for suicidal ideation and attempts among LBC and NLBC during the COVID-19 epidemic. With regard to the differences between LBC and NLBC, the use of maladaptive strategies and age might be vital factors for suicide prevention measures directed specifically toward LBC, whereas interventions sensitive to gender and perceived social economic status should be specifically designed for NLBC amid the COVID-19 pandemic.
Identification of Photoperiod-Induced LncRNAs and mRNAs in Pituitary Pars Tuberalis of Sheep
Authors: Xia Qing , Chu Mingxing , He Xiaoyun , Liu Qiuyue , Zhang Xiaosheng , Zhang Jinlong , Guo Xiaofei , Di Ran
Published: August 2021

The pituitary pars tuberalis (PT) is the regulating center of seasonal reproduction, which can sense the melatonin signal and eventually cause downstream changes of GnRH secretion through TSHβ. Recently, lncRNAs have been identified in animal reproductive-related tissues, and they play important roles in reproductive regulation. Therefore, in this study, we expect to identify photoperiod-induced lncRNAs and genes in pituitary PT of sheep by comparison of expression profiles between short photoperiod (SP) and long photoperiod (LP). Through RNA-Seq, a total of 55,472 lncRNAs were identified in pituitary PT of Sunite ewes. The number of differentially expressed (DE) genes and lncRNAs between SP and LP increased gradually with the extension of LP (from LP7 to LP42). The notable LP-induced candidate genes included EYA3, TSHB, SIX1, DCT, VMO1, AREG, SUV39H2, and EZH2, and SP-induced genes involved ENSOARG00000012585, CHGA, FOS, SOCS3, and TH. In enriched pathways for DE genes and lncRNA target genes between SP and LP, the reproduction- and circadian-related pathways were highlighted. In addition, the interactome analysis of lncRNAs and their targets implied that MSTRG.209166 and its trans-target TSHB, MSTRG.288068 and its cis-target SIX1, and ENSOARG00000026131 and its cis-target TH might participate in regulation of seasonal reproduction. Together, these results will help to determine important photoperiod-induced lncRNAs and genes and give us some new insights into the epigenetic regulation of seasonal reproduction in sheep.
The Effects of Mycophenolate on the Formation of Granulation Tissue Post-operatively in Canine Tracheal Stent Patients (2014–2020)
Authors: Barber Kevin F. , Loughin Catherine A. , Marino Dominic J. , Lesser Martin
Published: August 2021

Objectives: To determine if mycophenolate mofetil reduces the incidence and severity of granulation tissue in-growth in canine tracheal stent patients.

Study design: Randomized clinical trial.

Animals: 111 dogs from the hospital population.

Methods: Client-owned dogs that received an endoluminal self-expanding tracheal stent for canine tracheal collapse between 2014 and 2020 were randomly assigned into one of two treatment groups. Control group medication protocol consisted of prednisone 0.5 mg/kg PO BID/SID/EOD × 30 days, hydrocodone 0.25 mg/kg PO TID × 30 days, and cefovecin 8 mg/kg SQ post-placement. Mycophenolate group medication protocol was identical to the control group medication protocol with the addition of mycophenolate mofetil 10 mg/kg PO BID × 30 days, SID for life. Recheck tracheoscopy was performed at 1, 3, and 6 months post-stent placement. Presence and severity of granulation tissue were determined by tracheoscopy and were recorded as a percentage of tracheal lumen obstruction by blinded evaluators (none present, <25%, >25–50%, and >50%).

Results: At none of the three time points was there a statistically significant difference in grade between controls and those receiving mycophenolate (p = 0.467, p = 0.330, and p = 0.410).

Conclusions and Clinical Significance: Our results suggest that mycophenolate can be safely given to these patients but do not support that its administration will reduce the incidence and severity of granulation tissue. Although a difference was observed in the severity of granulation tissue between the two groups, loss to follow-up may have influenced conclusions. A larger study would be warranted to further evaluate the effect of mycophenolate on the development of granulation tissue.
Thallium: A Polluting Metal of New Generation. Its Voltammetric Determination in Herbal Medicines in Presence of Metal Interferences
Authors: Melucci Dora , Casolari Sonia , Locatelli Marcello , Locatelli Clinio
Published: August 2021

The present paper reports a new application: the voltammetric determination in herbal medicines of ultra-trace thallium(I), in the presence of lead(II), tin(II) and antimony(III) as interfering metals, by square wave anodic stripping voltammetry (SWASV). A conventional three-electrodes voltammetric cell was employed with a stationary hanging mercury drop electrode (HMDE) as working electrode and a platinum electrode and an Ag|AgCl|KClsatd. electrode as auxiliary and reference electrodes, respectively. The supporting electrolyte was 0.5 mol L−1 ammonium citrate buffer pH 6.5 + 7.3·10−3 mol L−1 EDTA-Na2. The analytical procedure was verified by the analysis of the standard reference materials: spinach Leaves NIST-SRM 1570a and tomato leaves NIST-SRM 1573a from National Institute of Standards and Technology. Precision and trueness, expressed as relative standard deviation and relative error, respectively, were generally lower than 7% in all cases. Once set up on the standard reference materials, the analytical procedure was transferred and applied to herbal medicines samples—Taraxacun officinale weber, Eucalyptus globulus and Harpagophytum procumbens DC—sold on the market. A critical comparison with spectroscopic measurements is also discussed.
“The Show Must Go On”. Ethnography of the Art Market Facing the COVID-19 Pandemic
Authors: Saint-Raymond Léa
Published: August 2021

This paper aims at understanding, from the inside, the impact of the COVID-19 pandemic and the accompanying restrictive administrative measures on the art market. It is based on the interviews and ethnographic surveys made by graduate students from the Ecole du Louvre, from September 2020 to May 2021. This methodology makes it possible to demonstrate that, during the crisis, art market professionals were driven by the motto “the show must go on”. On the one hand, they wished to keep a straight face and remain silent on their individual difficulties, preferring to talk about their vocation and the positive effects of the crisis. On the other hand, the commercial activity continued despite everything; if the pandemic accelerated the digital turn of the art market, the physical contact with the works and the collectors remained primordial. The art market thus remained physical but accelerated its digital turn. The proportion of each interactional framework—physical and digital—is still uncertain, difficult to measure today and to predict in the long run.
A Study on the Appropriateness of the Drought Index Estimation Method Using Damage Data from Gyeongsangnamdo, South Korea
Authors: Song Youngseok , Park Moojong
Published: August 2021

Drought is one of the disasters that causes the most extensive and severe damage. Therefore, drought prevention must be performed for administrative districts at the national level rather than the individual level. This study proposes a drought index estimation method for Gyeongsangnamdo, South Korea that evaluates its appropriateness through a comparison with damage data over several years. The standardized precipitation index (SPI) by duration was used as the drought index that was estimated for 13 rainfall stations located inside and outside Gyeonsangnam-do using the Thiessen method and cluster analysis. The SPI of Gyeongsangnamdo by duration based on the Thiessen method and cluster analysis for the years when drought damage occurred was compared with an SPI value of −2.0, which is the extreme drought condition, to determine its appropriateness. For the evaluation of the appropriateness, the performance indicators of the mean absolute deviation (MAD), mean squared error (MSE), and root mean square error (RMSE) were used. The analysis results showed that SPI by duration based on the cluster analysis method was more appropriate for damage data over many years than that based on the Thiessen method.
Identification of CNGB1 as a Predictor of Response to Neoadjuvant Chemotherapy in Muscle-Invasive Bladder Cancer
Authors: Hepburn Anastasia C. , Lazzarini Nicola , Veeratterapillay Rajan , Wilson Laura , Bacardit Jaume , Heer Rakesh
Published: August 2021

Cisplatin-based neoadjuvant chemotherapy (NAC) is recommended prior to radical cystectomy for muscle-invasive bladder cancer (MIBC) patients. Despite a 5–10% survival benefit, some patients do not respond and experience substantial toxicity and delay in surgery. To date, there are no clinically approved biomarkers predictive of response to NAC and their identification is urgently required for more precise delivery of care. To address this issue, a multi-methods analysis approach of machine learning and differential gene expression analysis was undertaken on a cohort of 30 MIBC cases highly selected for an exquisitely strong response to NAC or marked resistance and/or progression (discovery cohort). RGIFE (ranked guided iterative feature elimination) machine learning algorithm, previously demonstrated to have the ability to select biomarkers with high predictive power, identified a 9-gene signature (CNGB1, GGH, HIST1H4F, IDO1, KIF5A, MRPL4, NCDN, PRRT3, SLC35B3) able to select responders from non-responders with 100% predictive accuracy. This novel signature correlated with overall survival in meta-analysis performed using published NAC treated-MIBC microarray data (validation cohort 1, n = 26, Log rank test, p = 0.02). Corroboration with differential gene expression analysis revealed cyclic nucleotide-gated channel, CNGB1, as the top ranked upregulated gene in non-responders to NAC. A higher CNGB1 immunostaining score was seen in non-responders in tissue microarray analysis of the discovery cohort (n = 30, p = 0.02). Kaplan-Meier analysis of a further cohort of MIBC patients (validation cohort 2, n = 99) demonstrated that a high level of CNGB1 expression associated with shorter cancer specific survival (p < 0.001). Finally, in vitro studies showed siRNA-mediated CNGB1 knockdown enhanced cisplatin sensitivity of MIBC cell lines, J82 and 253JB-V. Overall, these data reveal a novel signature gene set and CNGB1 as a simpler proxy as a promising biomarker to predict chemoresponsiveness of MIBC patients.
Application of Community Detection Algorithm to Investigate the Correlation between Imaging Biomarkers of Tumor Metabolism, Hypoxia, Cellularity, and Perfusion for Precision Radiotherapy in Head and Neck Squamous Cell Carcinomas
Authors: Paudyal Ramesh , Grkovski Milan , Oh Jung Hun , Schöder Heiko , Nunez David Aramburu , Hatzoglou Vaios , Deasy Joseph O. , Humm John L. , Lee Nancy Y. , Shukla-Dave Amita
Published: August 2021

The present study aimed to investigate the correlation at pre-treatment (TX) between quantitative metrics derived from multimodality imaging (MMI), including 18F-FDG-PET/CT, 18F-FMISO-PET/CT, DW- and DCE-MRI, using a community detection algorithm (CDA) in head and neck squamous cell carcinoma (HNSCC) patients. Twenty-three HNSCC patients with 27 metastatic lymph nodes underwent a total of 69 MMI exams at pre-TX. Correlations among quantitative metrics derived from FDG-PET/CT (SUL), FMSIO-PET/CT (K1, k3, TBR, and DV), DW-MRI (ADC, IVIM [D, D*, and f]), and FXR DCE-MRI [Ktrans, ve, and τi]) were investigated using the CDA based on a “spin-glass model” coupled with the Spearman’s rank, ρ, analysis. Mean MRI T2 weighted tumor volumes and SULmean values were moderately positively correlated (ρ = 0.48, p = 0.01). ADC and D exhibited a moderate negative correlation with SULmean (ρ ≤ −0.42, p < 0.03 for both). K1 and Ktrans were positively correlated (ρ = 0.48, p = 0.01). In contrast, Ktrans and k3max were negatively correlated (ρ = −0.41, p = 0.03). CDA revealed four communities for 16 metrics interconnected with 33 edges in the network. DV, Ktrans, and K1 had 8, 7, and 6 edges in the network, respectively. After validation in a larger population, the CDA approach may aid in identifying useful biomarkers for developing individual patient care in HNSCC.
Treatment-Related Adverse Events of Chimeric Antigen Receptor T-Cell (CAR T) in Clinical Trials: A Systematic Review and Meta-Analysis
Authors: Lei Wen , Xie Mixue , Jiang Qi , Xu Nengwen , Li Ping , Liang Aibin , Young Ken H. , Qian Wenbin
Published: August 2021

Chimeric antigen receptors T (CAR-T) cell therapy of cancer is a rapidly evolving field. It has been shown to be remarkably effective in cases of hematological malignancies, and its approval by the FDA has significantly increased the enthusiasm for wide clinical usage and development of novel CAR-T therapies. However, it has also challenged physicians and investigators to recognize and deal with treatment-associated toxicities. A total of 2592 patients were included from 84 eligible studies that were systematically searched and reviewed from the databases of PubMed, de, the American Society of Hematology and the Cochrane Library. The meta-analysis and subgroup analysis by a Bayesian logistic regression model were used to evaluate the incidences of therapy-related toxicities such as cytokine release syndrome (CRS) and neurological symptoms (NS), and the differences between different targets and cancer types were analyzed. The pooled all-grade CRS rate and grade ≥ 3 CRS rate was 77% and 29%, respectively, with a significantly higher incidence in the hematologic malignancies (all-grade: 81%; grade ≥ 3: 29%) than in solid tumors (all-grade: 37%; grade ≥ 3: 19%). The pooled estimate NS rate from the individual studies were 40% for all-grade and 28% for grade ≥ 3. It was also higher in the hematologic subgroup than in the solid tumors group. The subgroup analysis by cancer type showed that higher incidences of grade ≥ 3 CRS were observed in anti-CD19 CAR-T therapy for ALL and NHL, anti-BCMA CAR-T for MM, and anti-CEA CAR-T for solid tumors, which were between 24–36%, while higher incidences of grade ≥ 3 NS were mainly observed in CD19-ALL/NHL (23–37%) and BCMA-MM (12%). Importantly, subgroup analysis on anti-CD19 CAR-T studies showed that young patients (vs. adult patients), allologous T cell origin (vs. autologous origin), gamma retrovirus vector, and higher doses of CAR-T cells were associated with high-grade CRS. On the other hand, the patients with NHL (vs ALL), administered with higher dose of CAR-T, and adult patients (vs. young patients) had an increased incidence of grade ≥ 3 NS events. This study offers a comprehensive summary of treatment-related toxicity and will guide future clinical trials and therapeutic designs investigating CAR T cell therapy.
Consistency of Pituitary Adenoma: Prediction by Pharmacokinetic Dynamic Contrast-Enhanced MRI and Comparison with Histologic Collagen Content
Authors: Kamimura Kiyohisa , Nakajo Masanori , Bohara Manisha , Nagano Daigo , Fukukura Yoshihiko , Fujio Shingo , Takajo Tomoko , Tabata Kazuhiro , Iwanaga Takashi , Imai Hiroshi , Nickel Marcel Dominik , Yoshiura Takashi
Published: August 2021

Prediction of tumor consistency is valuable for planning transsphenoidal surgery for pituitary adenoma. A prospective study was conducted involving 49 participants with pituitary adenoma to determine whether quantitative pharmacokinetic analysis of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) is useful for predicting consistency of adenomas. Pharmacokinetic parameters in the adenomas including volume of extravascular extracellular space (EES) per unit volume of tissue (ve), blood plasma volume per unit volume of tissue (vp), volume transfer constant between blood plasma and EES (Ktrans), and rate constant between EES and blood plasma (kep) were obtained. The pharmacokinetic parameters and the histologic percentage of collagen content (PCC) were compared between soft and hard adenomas using Mann–Whitney U test. Pearson’s correlation coefficient was used to correlate pharmacokinetic parameters with PCC. Hard adenomas showed significantly higher PCC (44.08 ± 15.14% vs. 6.62 ± 3.47%, p < 0.01), ve (0.332 ± 0.124% vs. 0.221 ± 0.104%, p < 0.01), and Ktrans (0.775 ± 0.401/min vs. 0.601 ± 0.612/min, p = 0.02) than soft adenomas. Moreover, a significant positive correlation was found between ve and PCC (r = 0.601, p < 0.01). The ve derived using DCE-MRI may have predictive value for consistency of pituitary adenoma.
Application of Artificial Intelligence in the MRI Classification Task of Human Brain Neurological and Psychiatric Diseases: A Scoping Review
Authors: Zhang Zhao , Li Guangfei , Xu Yong , Tang Xiaoying
Published: August 2021

Artificial intelligence (AI) for medical imaging is a technology with great potential. An in-depth understanding of the principles and applications of magnetic resonance imaging (MRI), machine learning (ML), and deep learning (DL) is fundamental for developing AI-based algorithms that can meet the requirements of clinical diagnosis and have excellent quality and efficiency. Moreover, a more comprehensive understanding of applications and opportunities would help to implement AI-based methods in an ethical and sustainable manner. This review first summarizes recent research advances in ML and DL techniques for classifying human brain magnetic resonance images. Then, the application of ML and DL methods to six typical neurological and psychiatric diseases is summarized, including Alzheimer’s disease (AD), Parkinson’s disease (PD), major depressive disorder (MDD), schizophrenia (SCZ), attention-deficit/hyperactivity disorder (ADHD), and autism spectrum disorder (ASD). Finally, the limitations of the existing research are discussed, and possible future research directions are proposed.
Frederick II of Hohenstaufen (1208–1250)
Authors: Vagnoni Mirko
Published: August 2021

Frederick II of Hohenstaufen, King of Sicily (1208–1250). Frederick II of Hohenstaufen was the second king of the Swabian dynasty to sit on the throne of Sicily. He was crowned in 1198, but, in consideration of his young age, he only ruled independently from 1208 to 1250 (the year of his death). He not only held the title of King of Sicily but also was the King of Germany (or of the Romans), the King of Jerusalem, and, above all, Emperor of the Holy Roman Empire. His most relevant and innovative iconographic representations were in Southern Italy. For this reason, we focus on the images in this geographical context. In particular, we have nine official (that is, those commissioned directly by him or his entourage) representations of him: the bull (in three main versions), the seal (in three main versions), five coins (four denari and one augustale), the statue of the Capua Gate, and the lost image of the imperial palace in Naples.
Surface Hydrophobization of Block-Shaped Wood with Rapid Benzylation
Authors: Abe Mitsuru , Seki Masako , Miki Tsunehisa , Nishida Masakazu
Published: August 2021

With the aim of utilizing wood as a carbon cycle-oriented material, the improvement of hydrophobicity has been actively studied to solve manufacturing problems, such as dimensional stability and biodeterioration resistance. The introduction of benzyl group is a promising chemical modification for hydrophobizing wood. However, conventional benzylation methods are not suitable for industrial applications because they require high temperature and long reaction times. In this study, a novel method was developed for quickly benzylating the surface of block-shaped wood using an aqueous solution of tetra-n-butylphosphonium hydroxide as a pretreatment solvent and no heat. The color and shape of the benzylated wood was almost unchanged from that before the treatment. Analysis of the resulting chemical structure suggested that the developed method causes less damage to carbohydrates compared with the conventional method, which involves heating and stirring. The proposed method successfully imparted hydrophobicity and thermoplasticity to the benzylated wood surface. Furthermore, hydrophobicity of the benzylated wood was further improved by a simple heat treatment for only approximately 5 min. The water contact angle became ≥110° and remained almost unchanged even after 1 min after water dropping.
Structural Characteristics of the Main Resinous Stands from Southern Carpathians, Romania
Authors: Murariu Gabriel , Dinca Lucian , Tudose Nicu , Crisan Vlad , Georgescu Lucian , Munteanu Dan , Dragu Mihai Daniel , Rosu Bogdan , Mocanu George Dănuţ
Published: August 2021

The purpose of this study, which contains historical data recorded over a period of 40 years, was to identify the main factors that influence and control the level of wood mass production. The main reason was to optimize the management of forest areas and was driven by the necessity to identify factors that can influence most of the volume produced by coniferous forests located in southeast Europe. The data was collected between1980 and 2005 at the National Institute for Research and Development in Forestry, for forests located in the Southern Carpathians, Romania. The studied data refer to the parameters that model forest structure for spruce, fir, pine, and larch. These are the main resinous species found in the Southern Carpathians. The total area covered by these forests is 143,431 ha. At the forest species level, the analysis consists of 16,162 records (corresponding to the elements of the trees), covering an area of 45,008 ha for fir, 4711 ha for larch, 81,995 ha for spruce, and 11,717 ha for pine. The aim of this research has been to investigate and to assess the impact and magnitude of abiotic factors such as altitude and field aspect on forest structures from the main resinous stands located in the Southern Carpathians. Taking into account the size of the database as well as the duration for collecting data, a complete statistical and systematic approach was considered optimum. This resulted from our wish to emphasize and evaluate the influence of each analysed factor on the wood mass production level. The relationship between abiotic factors and forest structure has been analysed by using a systematic statistical approach in order to provide a useful theoretical reference for the improvement of forest management practices in the context of multiple climatic, environmental, and socio-economic challenges. These common characteristics have been found by applying ANOVA and multivariate statistical methods such as PCA and FA methods. A series of parameters were considered in this investigation, namely altitude (ALT), forest site type (TS), forest type (TP), consistency (CONS) etc. In order to obtain a complete image, we have also applied multivariate analysis methods that emphasize the effect size for each database parameter. At such a level of recorded data, the statistical approach ensures a factor level of p <0.001 while the accuracy in evaluating effect size is increased. As such, they influence the spreading and structure of the studied resinous stands to a higher degree, regardless of species.
Determining Statistically Robust Changes in Ungulate Browsing Pressure as a Basis for Adaptive Wildlife Management
Authors: Bödeker Kai , Ammer Christian , Knoke Thomas , Heurich Marco
Published: August 2021

Ungulate browsing has a major impact on the composition and structure of forests. Repeatedly conducted, large-scale regeneration inventories can monitor the extent of browsing pressure and its impacts on forest regeneration development. Based on the respective results, the necessity and extent of wildlife management activities such as hunting, fencing, etc., can be identified at a landscape scale. However, such inventories have rarely been integrated into wildlife management decision making. In this article, we evaluate a regeneration inventory method which was carried out in the Bavarian Forest National Park between 2007 and 2018. We predict the browsing impact by calculating browsing probabilities using a logistic mixed effect model. To provide wildlife managers with feedback on their activities, we developed a test which can assess significant changes in browsing probability between different inventory periods. To find the minimum observable browsing probability change, we simulated ungulate browsing based on the data of a potential browsing indicator species (Sorbus aucuparia) in the National Park. Sorbus aucuparia is evenly distributed, commonly found, selectively browsed and meets the ecosystem development objectives in our study area. We were able to verify a browsing probability change down to ±5 percentage points with a sample size of about 1,000 observations per inventory run. In view of the size of the National Park and the annual fluctuations in browsing pressure, this estimation accuracy seems sufficient. In seeking the maximal cost-efficiency, we were able to reduce this sample size in a sensitivity analysis by about two thirds without severe loss of information for wildlife management. Based on our findings, the presented inventory method combined with our evaluation tool has the potential to be a robust and efficient instrument to assess the impact of herbivores that are in the National Park and other regions.
Acceptance and Commitment Therapy for Children with Special Health Care Needs and Their Parents: A Systematic Review and Meta-Analysis
Authors: Parmar Arpita , Esser Kayla , Barreira Lesley , Miller Douglas , Morinis Leora , Chong Yuen-Yu , Smith Wanda , Major Nathalie , Church Paige , Cohen Eyal , Orkin Julia
Published: August 2021

Context: Acceptance and Commitment Therapy (ACT) is an emerging treatment for improving psychological well-being. Objective: To summarize research evaluating the effects of ACT on psychological well-being in children with special health care needs (SHCN) and their parents. Data Sources: An electronic literature search was conducted in PubMed, Web of Science, Ovid/EMBASE and PsycINFO (January 2000–April 2021). Study Selection: Included were studies that assessed ACT in children with SHCN (ages 0–17y) and/or parents of children with SHCN and had a comparator group. Data Extraction: Descriptive data were synthesized and presented in a tabular format, and data on relevant outcomes (e.g., depressive symptoms, stress, avoidance and fusion) were used in the meta-analyses to explore the effectiveness of ACT (administered independently with no other psychological therapy) compared to no treatment. Results: Ten studies were identified (child (7) and parent (3)). In children with SHCN, ACT was more effective than no treatment at helping depressive symptoms (standardized mean difference [SMD] = −4.27, 95% CI: −5.20, −3.34; p < 0.001) and avoidance and fusion (SMD = −1.64, 95% CI: −3.24, −0.03; p = 0.05), but not stress. In parents of children with SHCN, ACT may help psychological inflexibility (SMD = −0.77, 95% CI: −1.07, −0.47; p < 0.01). Limitations: There was considerable statistical heterogeneity in three of the six meta-analyses. Conclusions: There is some evidence that ACT may help with depressive symptoms in children with SHCN and psychological inflexibility in their parents. Research on the efficacy of ACT for a variety of children with SHCN and their parents is especially limited, and future research is needed.
Association of Parental Socioeconomic Status and Physical Activity with Development of Arterial Stiffness in Prepubertal Children
Authors: Lona Giulia , Hauser Christoph , Bade Svea , Köchli Sabrina , Infanger Denis , Endes Katharina , Faude Oliver , Hanssen Henner
Published: August 2021

The present study examined the prospective association of parental household income, education level, migration background, and physical activity (PA) behavior with the development of pulse wave velocity (PWV) in prepubertal children. A total of 223 children (initial age 6–8 years) were included in this prospective school-based cohort study from 2014 to 2018. Parental socioeconomic status, migration background, and PA behavior were assessed by the use of questionnaires at both times points. PWV was measured by an oscillometric device at follow-up (2018). No significant association of household income, education level, and parental migration background with PWV in children after four years was found. However, a high level of maternal PA was related to a lower childhood PWV at follow-up (mean (95% CI) 4.6 (4.54–4.66) m/s) compared to children of mothers with a low PA behavior (mean (95% CI) 4.7 (4.64–4.77) m/s) (p = 0.049). Children of mothers with a high PA level revealed a beneficial arterial stiffness after four years. Little evidence for an association of socioeconomic status and migration background with childhood arterial stiffness was found. Increased parental PA seems to support the development of childhood vascular health and should be considered in the generation of future primary prevention strategies of childhood cardiovascular health.
The main effects and application of glucocorticosteroids in clinical practice. A multidisciplinary approach
Authors: Kanner I.D. , Khafizullina G.R. , Kanner E.V. , Maksimov M.L.
Published: August 2021

Glucocorticosteroids are hormones produced by the adrenal cortex. The term also refers to semi-synthetic drugs such as prednisolone, dexamethasone and other drugs that are derivatives of hydrocortisone, the most active natural glucocorticosteroid. Cortisone is a biologically inactive compound that is converted to hydrocortisone in the liver. Both natural glucocorticosteroids have mineralocorticoid activity, but weaker than genuine mineralocorticoids.