bluuebunny/crossref_metadata_2025 huggingface dataset:
Dynamics of Thermolysis and Skin Microstructure in Water Buffaloes Reared in Humid Tropical Climate—A Microscopic and Thermographic Study
Authors: Vilela Reíssa Alves , Lourenço Junior José de Brito , Jacintho Manuel Antonio Chagas , Barbosa Antonio Vinícius Correa , Pantoja Messy Hannear de Andrade , Oliveira Carlos Magno Chaves , Garcia Alexandre Rossetto
Published: May 2022

The thermolytic capacity test is used to assess the adaptability of animals to existing environmental conditions. However, there is insufficient information on the relationship between histomorphometry and adaptability of buffaloes. Thus, this study aimed to assess the use of thermolysis pathways by buffaloes reared in a hot and humid environment so as to understand the relationships between environment, skin morphological characteristics, and heat storage, as well as the intensity and proportionality of use of its ways of dissipating heat to maintain homeothermy. The heat tolerance test, associated with the evaluations via infrared thermography, was applied to 10 female Murrah buffaloes and tegument histomorphometry was carried out. The animals exhibited very high heat tolerance with an average of 9.66 ± 0.21 and used thermal polypnea as the main heat dissipation pathway. Their mean skin thickness was 6.03 ± 1.16 mm and the active sweat and sebaceous gland tissue were 1.57 ± 0.38% and 1.08 ± 0.39%, respectively. The buffaloes exhibited a positive correlation between eyeball temperature and internal body temperature (r = 0.84523, p < 0.0001) and a negative correlation between respiratory rate and skin thickness (r = −0.73371, p = 0.0157). The high thermolytic capacity in shade conditions confirms the importance of access to shade in buffalo rearing systems in tropical regions.
A Change Management Approach with the Support of the Balanced Scorecard and the Utilization of Artificial Neural Networks
Authors: Psarras Alkinoos , Anagnostopoulos Theodoros , Salmon Ioannis , Psaromiligkos Yannis , Vryzidis Lazaros
Published: May 2022

Artificial Intelligence (AI) has revolutionized the way organizations face decision-making issues. One of these crucial elements is the implementation of organizational changes. There has been a wide-spread adoption of AI techniques in the private sector, whereas in the public sector their use has been recently extended. One of the greatest challenges that European governments have to face is the implementation of a wide variety of European Union (EU) funding programs which have evolved in the context of the EU long-term budget. In the current study, the Balanced Scorecard (BSC) and Artificial Neural Networks (ANNs) are intertwined with forecasting the outcomes of a co-financed EU program by means of its impact on the non-financial measures of the government body that materialized it. The predictive accuracy of the present model advanced in this research study takes into account all the complexities of the business environment, within which the provided dataset is produced. The outcomes of the study showed that the measures taken to enhance customer satisfaction allows for further improvement. The utilization of the proposed model could facilitate the decision-making process and initiate changes to the administrational issues of the available funding programs.
Optimal Aggressive Constrained Trajectory Synthesis and Control for Multi-Copters
Authors: Liu Tsung-Liang , Subbarao Kamesh
Published: May 2022

In this paper, we propose a novel time and control effort optimal aggressive trajectory synthesis and control design methodology. The trajectory synthesis is a modified minimum snap design but with specific position and orientation constraints on a multi-copter, such as flying through tight spaces (windows) at specific orientations. The paper also introduces a means to stitch together multiple flight segments, enforce smoothness, and minimize segment times as well as the overall time, thereby resulting in very aggressive and feasible trajectories. A novel analysis for a specific scenario when no yaw angle specifications are provided is conducted, wherein a trade-off results in additional aggressiveness. The control algorithms to follow these trajectories are based on an inverse dynamics approach. Several candidate high-fidelity simulations are performed to verify the effectiveness of the proposed approach.
New Method for Sugarcane (Saccharum spp.) Variety Resources Evaluation by Projection Pursuit Clustering Model
Authors: Zhao Yong , Zhang Yuebin , Zhao Jun , Zan Fenggang , Zhao Peifang , Deng Jun , Wu Caiwen , Liu Jiayong
Published: May 2022

In the breeding of new sugarcane varieties, the survey data do not always conform with a normal or linear distribution. To apply non-normal or non-linear data to evaluate new material requires a suitable evaluation model or method. The projection pursuit clustering (PPC) model is a statistical method that does not require making normal assumptions or other model assumptions on sample data, and is suitable to analyze high-dimensional, non-linear, and non-normal data. However, this model has been applied infrequently to crop variety evaluation. In this study, 103 varieties that have been bred over the last 70 years in China were planted, and their main industrial and agronomic traits were collected. Through the exploratory analysis of the data structure characteristics, the PPC model was used to evaluate these sugarcane varieties. The model provided good projection directions of agronomic and industrial traits, with accurate projection values. PPC models could evaluate sugarcane resources well, and the results were objective and reliable. Thus, the PPC model could be used as a new method for crop variety evaluation. At the same time, 51 excellent industrial and agronomic variety resources were screened for application in breeding.
Lucerne Proportion Regulates Competitive Uptake for Nitrogen and Phosphorus in Lucerne and Grass Mixtures on the Loess Plateau of China
Authors: Lu Yixiao , Mu Le , Yang Mei , Yang Huimin
Published: May 2022

Mixtures of legume and grass are used worldwide to gain advantages in forage production and ecological maintenance. However, competition for nutrients by legumes in mixtures has not been fully explored. The aim was to determine how the forage proportion affected nutrient competition in legume and grass mixtures. Treatments included two species combinations and five sowing ratios. Competitive ratios (CR) of lucerne for nitrogen (N) and phosphorus (P) over two grasses were assessed to analyze how the lucerne proportion in mixtures affected the competition. Total N and P uptake were mostly lower under timothy-containing mixtures (MPs) than under smooth bromegrass-containing mixtures (MBs). Proportions of both N (NM%) and P uptake (PM%) of lucerne were higher under MPs than under MBs. Higher total N and P uptake were found under half-lucerne mixtures (M5P5 or M5B5) than under other grasslands. The NM% and PM% tended to be higher under half-lucerne mixtures, although they showed little difference among mixtures. Lucerne CR was greater under MPs than under MBs, and was greater than grass CR when lucerne was in lower proportion in the mixtures. There was little difference in soil N density among grasslands of the same cut, whereas soil P density was variable. Competitiveness of lucerne depends largely on the initial sowing ratio. High ratios of lucerne significantly reduce soil P density, leading to P limitation and reduced N and P uptake. On the Loess Plateau of China, mixing lucerne with smooth bromegrass is recommended to increase the uptake and harvest of N and P, specifically at the sowing ratio of 5:5.
Values for the Mechanical Properties of Wheat, Maize and Wood Pellets for Use in Silo Load Calculations Involving Numerical Methods
Authors: Moya Manuel , Sánchez David , Villar-García José Ramón
Published: May 2022

The mechanical properties of the materials stored in agricultural silos determine the loads they generate under static and dynamic conditions. The present work describes the mechanical properties of wheat, maize and wood pellets. Direct shear and triaxial assay devices, and oedometers (all commonly used in geotechnical assays), were used to determine these materials’ internal angle of friction, Poisson’s ratio, Young’s modulus, apparent specific weight, etc. The results for wheat and maize were similar to those previously reported by other authors. For the wood pellets, the results for the internal angle of friction and apparent specific weight were also similar to those found in the literature. However, this is a relatively new type of material, and few results of this type have been reported, certainly not enough for reference values to be available. This work is the first to report this material’s dilatancy angle and Poisson’s ratio. A table is provided with suggested reference values for the studied mechanical properties of each of the test materials; these can be used in silo load calculations involving numerical methods.
Effects of Soil Properties and Microbiome on Highbush Blueberry (Vaccinium corymbosum) Growth
Authors: Zhou Yujie , Liu Yuqing , Zhang Xun , Gao Xiumei , Shao Tianyun , Long Xiaohua , Rengel Zed
Published: May 2022

Blueberry has high nutritional value and is favored by consumers, so the planting area is increasing. However, due to the influence of climate conditions and the edaphic environment, achieving high production and the healthy growth of blueberries has become a major problem. In this study, we collected soil and blueberry plants which had normal and limited growth to determine the underlying causes of poor growth by characterizing soil pH, EC, enzyme activities and the microbiome, plant growth properties, and root metabolites. The results showed that the pH of the blueberry rhizosphere soil was less than 6.0 in the case of plants growing well, and higher than 6.0 in case of plants growing poorly. The activities of acid phosphatase and invertase were significantly higher in the rhizosphere soil of the normally growing than growth-limited blueberry plants. The relative abundance of Proteobacteria and Saccharibacteria was higher in the rhizosphere soil of normally growing than growth-limited blueberry plants and they were positively correlated with activity of soil acid phosphatase. Ascomycota, as the dominant fungi, had the highest relative abundance in the rhizosphere soil of growth-limited blueberry plants. The six metabolites showing enrichment in the KEGG pathway analysis were thymidine, cholic acid, raffinose, p-salicylic acid, astaxanthin, and inosine. It was found that flavonoids were correlated positively with soil fungi abundance. The contents of flavonoids apin, rutin and epigallocatechin were significantly higher in roots of growth-limited than normally growing blueberry plants. The content of the flavonoid daidzin was significantly higher in the roots of poorly growing blueberries compared to normally growing ones. In conclusion, the growth of blueberry was significantly related to soil organic matter, soil enzyme activity and soil microbial community diversity.
Using High-Resolution Differential Cell Counts (HRDCCs) in Bovine Milk and Blood to Monitor the Immune Status over the Entire Lactation Period
Authors: Farschtschi Sabine , Hildebrandt Alex , Mattes Martin , Kirchner Benedikt , Pfaffl Michael W.
Published: May 2022

Differential cell counts in milk offer a deeper insight into the immunology of the mammary gland and might even provide information about the systemic health status of a dairy cow. Consequently, their potential as a diagnostic method to identify biomarkers has been a subject of research for quite some time. The objective of our study was to closely monitor the immune status of eight healthy dairy cows throughout their whole lactation. For this, high-resolution differential cell counts in milk and blood were determined by means of flow cytometry, which included 10 subpopulations of the 3 main populations of immune cells and their viability. Milk and blood samples were taken twice a week in the first 100 days after calving and once a week during the remaining lactation period: in total, 55 (52–57) blood and 55 (52–57) milk samples per animal. In addition, six well-established routine laboratory biomarkers, i.e., haptoglobin, calcium, and different metabolic parameters (non-esterified fatty acids, β-hydroxybutyric acid, bilirubin, and glutamate dehydrogenase), were analyzed in all blood samples. Furthermore, a standard differential blood cell count was performed on all blood samples. We found substantial differences between cell count progressions in the blood and milk. The distribution of cell populations in the blood remained mostly stable throughout the lactation, albeit at different individual levels. Several cell populations in the milk showed a noticeable dynamic over time, which caused a separation of different lactation stages in clustering analyses. Gamma delta T cells and CD4+ T cells in the milk stood out as they showed characteristic fluctuations during the course of lactation as well as minor changes in the case of inflammation. The determination of a differential cell count has the potential to be a sensitive diagnostic and prognostic tool in bovine milk. Further studies need to show to what extent the method is suitable for routine diagnostics and how to deal with animal-specific differences.
Perioperative Suppression of Schwann Cell Dedifferentiation Reduces the Risk of Adenomyosis Resulting from Endometrial–Myometrial Interface Disruption in Mice
Authors: Wang Xi , Liu Xishi , Guo Sun-Wei
Published: May 2022

We have recently demonstrated that endometrial–myometrial interface (EMI) disruption (EMID) can cause adenomyosis in mice, providing experimental evidence for the well-documented epidemiological finding that iatrogenic uterine procedures increase the risk of adenomyosis. To further elucidate its underlying mechanisms, we designed this study to test the hypothesis that Schwann cells (SCs) dedifferentiating after EMID facilitate the genesis of adenomyosis, but the suppression of SC dedifferentiation perioperatively reduces the risk. We treated mice perioperatively with either mitogen-activated protein kinase kinase (MEK)/extracellular-signal regulated protein kinase (ERK) or c-Jun N-terminal kinase (JNK) inhibitors or a vehicle 4 h before and 24 h, 48 h and 72 h after the EMID procedure. We found that EMID resulted in progressive SCs dedifferentiation, concomitant with an increased abundance of epithelial cells in the myometrium and a subsequent epithelial–mesenchymal transition (EMT). This EMID-induced change was abrogated significantly with perioperative administration of JNK or MEK/ERK inhibitors. Consistently, perioperative administration of a JNK or a MEK/ERK inhibitor reduced the incidence by nearly 33.5% and 14.3%, respectively, in conjunction with reduced myometrial infiltration of adenomyosis and alleviation of adenomyosis-associated hyperalgesia. Both treatments significantly decelerated the establishment of adenomyosis and progression of EMT, fibroblast-to-myofibroblast trans-differentiation and fibrogenesis in adenomyotic lesions. Thus, we provide the first piece of evidence strongly implicating the involvement of SCs in the pathogenesis of adenomyosis induced by EMID.
Dysregulation of Small Nucleolar RNAs in B-Cell Malignancies
Authors: Verbeek Martijn W. C. , Erkeland Stefan J. , van der Velden Vincent H. J.
Published: May 2022

Small nucleolar RNAs (snoRNAs) are responsible for post-transcriptional modification of ribosomal RNAs, transfer RNAs and small nuclear RNAs, and thereby have important regulatory functions in mRNA splicing and protein translation. Several studies have shown that snoRNAs are dysregulated in human cancer and may play a role in cancer initiation and progression. In this review, we focus on the role of snoRNAs in normal and malignant B-cell development. SnoRNA activity appears to be essential for normal B-cell differentiation and dysregulated expression of sno-RNAs is determined in B-cell acute lymphoblastic leukemia, chronic lymphocytic leukemia, B-cell non-Hodgkin’s lymphoma, and plasma cell neoplasms. SnoRNA expression is associated with cytogenetic/molecular subgroups and clinical outcome in patients with B-cell malignancies. Translocations involving snoRNAs have been described as well. Here, we discuss the different aspects of snoRNAs in B-cell malignancies and report on their role in oncogenic transformation, which may be useful for the development of novel diagnostic biomarkers or therapeutic targets.
Development of a Self-Viscosity and Temperature-Compensated Technique for Highly Stable and Highly Sensitive Bead-Based Diffusometry
Authors: Chen Wei-Long , Chuang Han-Sheng
Published: May 2022

Brownian motion, which is a natural phenomenon, has attracted numerous researchers and received extensive studies over the past decades. The effort contributes to the discovery of optical diffusometry, which is commonly used for micro/nano particle sizing. However, the analysis uncertainty caused by the coupling relationship among particle diameter, temperature, and fluid viscosity usually poses a barrier to precise measurement. Preventing random background noise becomes the key to achieving a high level of accuracy in diffusometry detection. Recently, Janus particles have become known as an ideal tool for resolving the rotational Brownian motion. Followed by our previous study, the rotational Brownian motion and the translational Brownian motion can be separately measured using the Janus particles. Accordingly, a simple self-viscosity and temperature-compensated technique based on the delicate removal of temperature and fluid viscosity variations through particle tracking was first proposed in this study. Consequently, the translational Brownian motion was expressed in terms of particle trajectory, whereas the rotational Brownian motion was expressed in terms of the blinking signal from the Janus particles. The algorithm was verified simulatively and experimentally in temperature (10 °C to 40 °C) and viscosity-controlled (1 mPa·s to 5 mPa·s) fields. In an evaluation of biosensing for a target protein, IFN-γ, the limit of detection of the proposed self-compensated diffusometry reached 0.45 pg/mL, whereas its uncertainties of viscosity and temperature were 96 and 15-fold lower than the pure the rotational Brownian motion counterpart, respectively. The results indicated the low-uncertainty and high-accuracy biosensing capability resulting from the self-viscosity and temperature-compensated technique. This research will provide a potential alternative to future similar bead-based immunosensing, which requires ultra-high stability and sensitivity.
Recent Applications of Artificial Intelligence from Histopathologic Image-Based Prediction of Microsatellite Instability in Solid Cancers: A Systematic Review
Authors: Alam Mohammad Rizwan , Abdul-Ghafar Jamshid , Yim Kwangil , Thakur Nishant , Lee Sung Hak , Jang Hyun-Jong , Jung Chan Kwon , Chong Yosep
Published: May 2022

Cancers with high microsatellite instability (MSI-H) have a better prognosis and respond well to immunotherapy. However, MSI is not tested in all cancers because of the additional costs and time of diagnosis. Therefore, artificial intelligence (AI)-based models have been recently developed to evaluate MSI from whole slide images (WSIs). Here, we aimed to assess the current state of AI application to predict MSI based on WSIs analysis in MSI-related cancers and suggest a better study design for future studies. Studies were searched in online databases and screened by reference type, and only the full texts of eligible studies were reviewed. The included 14 studies were published between 2018 and 2021, and most of the publications were from developed countries. The commonly used dataset is The Cancer Genome Atlas dataset. Colorectal cancer (CRC) was the most common type of cancer studied, followed by endometrial, gastric, and ovarian cancers. The AI models have shown the potential to predict MSI with the highest AUC of 0.93 in the case of CRC. The relatively limited scale of datasets and lack of external validation were the limitations of most studies. Future studies with larger datasets are required to implicate AI models in routine diagnostic practice for MSI prediction.
Prognostic Impact of Microscopic Extra-Thyroidal Extension (mETE) on Disease Free Survival in Patients with Papillary Thyroid Carcinoma (PTC)
Authors: Bouzehouane Nadia , Roy Pascal , Decaussin-Petrucci Myriam , Bertholon-Grégoire Mireille , Bully Chantal , Perrin Agnès , Lasolle Helene , Lifante Jean-Christophe , Borson-Chazot Françoise , Bournaud Claire
Published: May 2022

Background: This study assessed the risk of reduced disease-free survival (DFS) and poor clinical outcome in patients with papillary thyroid carcinomas (PTC) with microscopic extra-thyroidal extension (mETE), as compared to PTC patients without mETE. Methods: Retrospective analysis of a prospective database of patients treated by total thyroidectomy and radioactive iodine (RAI) with a five-year follow-up and tumors < 40 mm. In total, 303 patients were analyzed: 30.7% presented tumors with mETE, and 69.3% without. mETE was defined as extra-thyroidal invasion without skeletal muscle involvement. The primary outcome, DFS, was defined as the interval between initial treatment and any subsequent PTC-related treatment. The second outcome was the clinical status at five years. Results: In univariate analyses, the five-year DFS was significantly lower for tumors with mETE (62.4% versus 88.1%, p < 0.001). In multivariate analysis, mETE and massive lymph node involvement (LNI) were independent prognostic factors, associated respectively with a hazard ratio of 2.55 (95% CI 1.48–4.40) and 8.94 (95% CI 4.92–16.26). mETE was significantly associated with a pejorative clinical outcome at five years, i.e., biochemical/indeterminate response and structural persistence (Respectively OR 1.83 (95% CI 0.83; 4.06) and OR 4.92 (95% CI 1.87; 12.97)). Conclusion: Our results suggest that mETE is an independent poor prognosis factor of reduced DFS and predictive of poor clinical outcome.
Cancer Vaccination against Extracellular Vimentin Efficiently Adjuvanted with Montanide ISA 720/CpG
Authors: van Loon Karlijn , Huijbers Elisabeth J. M. , de Haan Jan David , Griffioen Arjan W.
Published: May 2022

Extracellular vimentin is a specific marker of the tumor vasculature, where it is secreted by tumor endothelial cells. Vaccination with a conjugate vaccine targeting extracellular vimentin was previously shown to induce a potent humoral immune response and tumor growth inhibition in mice. These data were obtained by vaccination using the toxic Freund’s adjuvant (FA) and are therefore not directly translatable into the clinic. In the present study, we aimed to investigate the potential of the biodegradable Montanide ISA 720 adjuvant. We tested Montanide either alone (MN) or supplemented with CpG 1826 (MN-C). Both adjuvant compositions, as well as FA, resulted in a significant tumor growth inhibition and decreased vessel density in the B16F10 melanoma tumor model. Vaccination of mice with either FA or MN-C resulted in an equally potent humoral immune response towards vimentin, while the antibody titers obtained with MN alone were significantly lower compared to FA. Vaccination coincided with the infiltration of immune cells. The highest number of intratumoral immune cells was seen in tumors from the MN-C group. Therefore, we conclude that Montanide ISA 720 supplemented with CpG allows efficient vaccination against extracellular vimentin, which is a prerequisite for the transfer of the vaccine into the clinic.
Risk Factors of Incident Lung Cancer in Patients with Non-Cystic Fibrosis Bronchiectasis: A Korean Population-Based Study
Authors: Kim Youlim , Han Kyungdo , Yoo Juhwan , Kang Hyung Koo , Park Tai Sun , Park Dong Won , Hong Ji Young , Moon Ji-Yong , Kim Sang-Heon , Kim Tae Hyung , Yoo Kwang Ha , Sohn Jang Won , Yoon Ho Joo , Choi Hayoung , Lee Hyun
Published: May 2022

Background: Patients with non-cystic fibrosis bronchiectasis have an increased risk of lung cancer, followed by higher mortality in this population. Because the risk factors of lung cancer have not been well identified, this study aimed to investigate the risk factors of lung cancer in individuals with newly diagnosed bronchiectasis. Methods: This cohort study using the Korean National Health Insurance Service database identified 7425 individuals with incident bronchiectasis among those who participated in the health screening exam in 2009. The cohort was followed from baseline to the date of incident: lung cancer, death, or until the end of the study period. We investigated the risk factors of lung cancer in participants with bronchiectasis using the Cox–proportional hazard models. Results: During median 8.3 years of follow-up duration, 1.9% (138/7425) developed lung cancer. In multivariable analyses, significant factors associated with increased risk of incident lung cancer included: males (adjusted hazard ratio [HR] = 3.54, 95% confidence interval [CI] = 2.17–5.79) than females, the overweight (adjusted HR = 1.55, 95% CI = 1.03–2.35) than the normal weight, current smokers (adjusted HR = 3.10, 95% CI = 2.00–4.79) than never smokers, participants living in the rural area (adjusted HR = 2.54, 95% CI = 1.68–3.85) than those living in the metropolitan area. Among comorbidities, chronic obstructive pulmonary disease was associated with an increased risk of lung cancer (adjusted HR = 1.46, 95% CI = 1.01–2.13) in participants with bronchiectasis. In contrast, mild alcohol consumption was associated with reduced risk of lung cancer (adjusted HR = 0.47, 95% CI = 0.29–0.74) in those with bronchiectasis. Conclusion: This Korean population-based study showed that males, current smoking, overweight, living in rural areas, and comorbid chronic obstructive pulmonary disease are associated with increased risk of lung cancer in individuals with bronchiectasis.
Associations between Normal Organs and Tumor Burden in Patients Imaged with Fibroblast Activation Protein Inhibitor-Directed Positron Emission Tomography
Authors: Kosmala Aleksander , Serfling Sebastian E. , Dreher Niklas , Lindner Thomas , Schirbel Andreas , Lapa Constantin , Higuchi Takahiro , Buck Andreas K. , Weich Alexander , Werner Rudolf A.
Published: May 2022

(1) Background: We aimed to quantitatively investigate [68Ga]Ga-FAPI-04 uptake in normal organs and to assess a relationship with the extent of FAPI-avid tumor burden. (2) Methods: In this single-center retrospective analysis, thirty-four patients with solid cancers underwent a total of 40 [68Ga]Ga-FAPI-04 PET/CT scans. Mean standardized uptake values (SUVmean) for normal organs were established by placing volumes of interest (VOIs) in the heart, liver, spleen, pancreas, kidneys, and bone marrow. Total tumor burden was determined by manual segmentation of tumor lesions with increased uptake. For tumor burden, quantitative assessment included maximum SUV (SUVmax), tumor volume (TV), and fractional tumor activity (FTA = TV × SUVmean). Associations between uptake in normal organs and tumor burden were investigated by applying Spearman’s rank correlation coefficient. (3) Results: Median SUVmean values were 2.15 in the pancreas (range, 1.05–9.91), 1.42 in the right (range, 0.57–3.06) and 1.41 in the left kidney (range, 0.73–2.97), 1.2 in the heart (range, 0.46–2.59), 0.86 in the spleen (range, 0.55–1.58), 0.65 in the liver (range, 0.31–2.11), and 0.57 in the bone marrow (range, 0.26–0.94). We observed a trend towards significance for uptake in the myocardium and tumor-derived SUVmax (ρ = 0.29, p = 0.07) and TV (ρ = −0.30, p = 0.06). No significant correlation was achieved for any of the other organs: SUVmax (ρ ≤ 0.1, p ≥ 0.42), TV (ρ ≤ 0.11, p ≥ 0.43), and FTA (ρ ≤ 0.14, p ≥ 0.38). In a sub-analysis exclusively investigating patients with high tumor burden, significant correlations of myocardial uptake with tumor SUVmax (ρ = 0.44; p = 0.03) and tumor-derived FTA with liver uptake (ρ = 0.47; p = 0.02) were recorded. (4) Conclusions: In this proof-of-concept study, quantification of [68Ga]Ga-FAPI-04 PET showed no significant correlation between normal organs and tumor burden, except for a trend in the myocardium. Those preliminary findings may trigger future studies to determine possible implications for treatment with radioactive FAP-targeted drugs, as higher tumor load or uptake may not lead to decreased doses in the majority of normal organs.
Systematic Review with Meta-Analysis: Comparison of the Risk of Hepatocellular Carcinoma in Antiviral-Naive Chronic Hepatitis B Patients Treated with Entecavir versus Tenofovir: The Devil in the Detail
Authors: Oh Hyunwoo , Lee Hyo Young , Kim Jihye , Kim Yoon Jun
Published: May 2022

Tenofovir disoproxil fumarate (TDF) and entecavir (ETV) are the preferred anti-viral agents used as first-line treatments for chronic hepatitis B (CHB). However, the efficacy of these agents in reducing the incidence of hepatocellular carcinoma (HCC) remains unclear. We conducted this meta-analysis to assess the efficacy of anti-viral agent on preventing HCC in CHB. Two investigators independently searched all relevant studies that examined the efficacy of anti-viral agent for preventing HCC using MEDLINE, Embase, and Cochrane Library databases through August 2021. The extracted data were analysed using a random-effects meta-analysis model based on the inverse-variance method (DerSimonian–Laird) and expressed as hazard ratio (HR) and 95% confidence interval (95% CI). We included 19 retrospective studies in the analysis. Although there was substantial heterogeneity between the studies, the overall pooled HR indicated that TDF significantly lowered the risk of HCC (HR: 0.72, 95% CI: 0.58–0.90, I2 = 66.29%). However, the pooled analysis of propensity score (PS)-matched subpopulations showed no significant differences (HR, 0.83; 95% CI, 0.65–1.06; I2 = 52.30%) between TDF and ETV. In a subgroup analysis, an interval of over three years in the start point of patient enrolment and excluding alcoholic liver disease patients significantly lowered the HCC risk associated with TDF. In conclusion, TDF may be more effective than ETV at reducing HCC incidence in treatment-naive CHB patients, but this effect was not consistent in the PS-matched subpopulation that reduced heterogeneity. As a result of subgroup analysis, the conflicting findings of previous studies may result from heterogeneous inclusion criteria. Further studies with standardised protocols are needed to reduce the residual heterogeneity.
Calreticulin and the Heart
Authors: Groenendyk Jody , Wang Wen-An , Robinson Alison , Michalak Marek
Published: May 2022

Calreticulin is an endoplasmic Ca2+ binding protein and molecular chaperone. As a cardiac embryonic gene, calreticulin is essential for heart development. The protein supports Ca2+-dependent signaling events that are critical to cardiomyocyte differentiation and cardiogenesis. The increased expression of calreticulin and endoplasmic reticulum/sarcoplasmic reticulum Ca2+ capacity produces cardiomyocytes with enhanced efficiency, and detrimental mechanical stretching of cardiac fibroblasts, leading to cardiac pathology. Deletion of the calreticulin gene in adult cardiomyocytes results in left ventricle dilation, an impaired electrocardiogram, and heart failure. These observations indicate that a well-adjusted endoplasmic reticulum and calreticulin-dependent Ca2+ pool in cardiomyocytes are critical for the maintenance of proper cardiac function.
Role of Cytoskeletal Diaphanous-Related Formins in Hearing Loss
Authors: Chiereghin Chiara , Robusto Michela , Massa Valentina , Castorina Pierangela , Ambrosetti Umberto , Asselta Rosanna , Soldà Giulia
Published: May 2022

Hearing relies on the proper functioning of auditory hair cells and on actin-based cytoskeletal structures. Diaphanous-related formins (DRFs) are evolutionarily conserved cytoskeletal proteins that regulate the nucleation of linear unbranched actin filaments. They play key roles during metazoan development, and they seem particularly pivotal for the correct physiology of the reproductive and auditory systems. Indeed, in Drosophila melanogaster, a single diaphanous (dia) gene is present, and mutants show sterility and impaired response to sound. Vertebrates, instead, have three orthologs of the diaphanous gene: DIAPH1, DIAPH2, and DIAPH3. In humans, defects in DIAPH1 and DIAPH3 have been associated with different types of hearing loss. In particular, heterozygous mutations in DIAPH1 are responsible for autosomal dominant deafness with or without thrombocytopenia (DFNA1, MIM #124900), whereas regulatory mutations inducing the overexpression of DIAPH3 cause autosomal dominant auditory neuropathy 1 (AUNA1, MIM #609129). Here, we provide an overview of the expression and function of DRFs in normal hearing and deafness.
Dysregulation of Immune Response Mediators and Pain-Related Ion Channels Is Associated with Pain-like Behavior in the GLA KO Mouse Model of Fabry Disease
Authors: Spitzel Marlene , Wagner Elise , Breyer Maximilian , Henniger Dorothea , Bayin Mehtap , Hofmann Lukas , Mauceri Daniela , Sommer Claudia , Üçeyler Nurcan
Published: May 2022

Fabry disease (FD) is a rare life-threatening disorder caused by deficiency of the alpha-galactosidase A (GLA) enzyme with a characteristic pain phenotype. Impaired GLA production or function leads to the accumulation of the cell membrane compound globotriaosylceramide (Gb3) in the neurons of the dorsal root ganglia (DRG) of FD patients. Applying immunohistochemistry (IHC) and quantitative real-time polymerase chain reaction (qRT PCR) analysis on DRG tissue of the GLA knockout (KO) mouse model of FD, we address the question of how Gb3 accumulation may contribute to FD pain and focus on the immune system and pain-associated ion channel gene expression. We show a higher Gb3 load in the DRG of young (<6 months) (p < 0.01) and old (≥12 months) (p < 0.001) GLA KO mice compared to old wildtype (WT) littermates, and an overall suppressed immune response in the DRG of old GLA KO mice, represented by a reduced number of CD206+ macrophages (p < 0.01) and lower gene expression levels of the inflammation-associated targets interleukin(IL)1b (p < 0.05), IL10 (p < 0.001), glial fibrillary acidic protein (GFAP) (p < 0.05), and leucine rich alpha-2-glycoprotein 1 (LRG1) (p < 0.01) in the DRG of old GLA KO mice compared to old WT. Dysregulation of immune-related genes may be linked to lower gene expression levels of the pain-associated ion channels calcium-activated potassium channel 3.1 (KCa3.1) and transient receptor potential ankyrin 1 channel (TRPA1). Ion channel expression might further be disturbed by impaired sphingolipid recruitment mediated via the lipid raft marker flotillin-1 (FLOT1). This impairment is represented by an increased number of FLOT1+ DRG neurons with a membranous expression pattern in old GLA KO mice compared to young GLA KO, young WT, and old WT mice (p < 0.001 each). Further, we provide evidence for aberrant behavior of GLA KO mice, which might be linked to dysregulated ion channel gene expression levels and disturbed FLOT1 distribution patterns. Behavioral testing revealed mechanical hypersensitivity in young (p < 0.01) and old (p < 0.001) GLA KO mice compared to WT, heat hypersensitivity in young GLA KO mice (p < 0.001) compared to WT, age-dependent heat hyposensitivity in old GLA KO mice (p < 0.001) compared to young GLA KO mice, and cold hyposensitivity in young (p < 0.001) and old (p < 0.001) GLA KO mice compared to WT, which well reflects the clinical phenotype observed in FD patients.
Dlx5/6 Expression Levels in Mouse GABAergic Neurons Regulate Adult Parvalbumin Neuronal Density and Anxiety/Compulsive Behaviours
Authors: Aouci Rym , El Soudany Mey , Maakoul Zakaria , Fontaine Anastasia , Kurihara Hiroki , Levi Giovanni , Narboux-Nême Nicolas
Published: May 2022

Neuronal circuits integrating Parvalbumin-positive GABAergic inhibitory interneurons (PV) are essential for normal brain function and are often altered in psychiatric conditions. During development, Dlx5 and Dlx6 (Dlx5/6) genes are involved in the differentiation of PV-interneurons. In the adult, Dlx5/6 continue to be expressed at low levels in most telencephalic GABAergic neurons, but their importance in determining the number and distribution of adult PV-interneurons is unknown. Previously, we have shown that targeted deletion of Dlx5/6 in mouse GABAergic neurons (Dlx5/6VgatCre mice) results in altered behavioural and metabolic profiles. Here we evaluate the consequences of targeted Dlx5/6 gene dosage alterations in adult GABAergic neurons. We compare the effects on normal brain of homozygous and heterozygous (Dlx5/6VgatCre and Dlx5/6VgatCre/+ mice) Dlx5/6 deletions to those of Dlx5 targeted overexpression (GABAergicDlx5/+ mice). We find a linear correlation between Dlx5/6 allelic dosage and the density of PV-positive neurons in the adult prelimbic cortex and in the hippocampus. In parallel, we observe that Dlx5/6 expression levels in GABAergic neurons are also linearly associated with the intensity of anxiety and compulsivity-like behaviours. Our findings reinforce the notion that regulation of Dlx5/6 expression is involved in individual cognitive variability and, possibly, in the genesis of certain neuropsychiatric conditions.
α-Glucosidase-Mediated Glucometer Readout for Portable Monitoring of Acarbose and Migliol
Authors: Zhang Hao , Yang Feng-Qing
Published: May 2022

The α-glucosidase inhibitor is regarded as one of the most important drugs for the treatment of diabetes, which can control postprandial blood glucose levels via prolonging the carbohydrate digestion time and retarding the carbohydrates’ absorption. The present work aims to establish a facile bioanalytical method, based on α-glucosidase catalyzing the hydrolysis of 2-O-alpha-D-Glucopyranosyl-L-ascorbic acid (AA-2G), for the quantification of acarbose and migliol using a personal glucose meter (PGM). The hydrolysis products (ascorbic acid and glucose) can trigger the reduction of K3[Fe(CN)6] to K4[Fe(CN)6] in the glucose test strips, which results in the formation of the electron, which can be measured by PGM. Thus, ascorbic acid and glucose can be simultaneously measured by a simplified and miniaturized PGM method. However, the products produced by the hydrolysis of AA-2G will be decreased after the addition of acarbose or migliol to inhibit the activity of α-glucosidase, thereby resulting in a decreased PGM readout. After being incubated with α-glucosidase for 3.0 min and enzymatic reaction for 5.0 min, the quantitative detection of acarbose and migliol can be achieved within the ranges of 1.0–30.0 μM with the limit of detection of 0.33 μM and 3.0–33.3 μM with the limit of detection of 1.0 μM, respectively. IC50 values for acarbose and migliol are calculated to be 10.0 μM and 16.0 μM, respectively. The recoveries of the acarbose and migliol spiked with three different concentrations (final concentrations of 10.0, 20.0, and 30.0 μM) in human serum sample are in the ranges of 89.6–114.5% and 93.9–106.5%, respectively. These results demonstrate that the developed PGM method may be useful in future studies on therapeutic monitoring of acarbose and migliol.
Psychosocial Characteristics and Experiences in Patients with Multiple Endocrine Neoplasia Type 2 (MEN2) and Medullary Thyroid Carcinoma (MTC)
Authors: Lockridge Robin , Bedoya Sima , Allen Taryn , Widemann Brigitte , Akshintala Srivandana , Glod John , Wiener Lori
Published: May 2022

Multiple Endocrine Neoplasia type 2 (MEN2) is a genetic cancer syndrome for which there are limited data pertaining to the quality of life and psychosocial experiences of persons affected. Medullary thyroid carcinoma (MTC) is a rare disease of the thyroid gland often associated with MEN2. MTC often progresses slowly and may present with a myriad of physical symptoms including hair loss, sleep disturbance, fatigue, weight changes, heart palpitations, and constipation or diarrhea. Like other cancers or rare, inheritable illnesses, patients with MEN2 and MTC may be at risk for psychosocial stressors. The current, cross-sectional study administered a structured psychosocial interview and The Distress Thermometer/Problem Checklist to 63 patients with MEN2 and MTC and their caregivers. Despite reports of overall good health, 46% of adults and 44% of youth reported that pain interferes with their daily life; 53% of adults and 59% of youth reported that pain interferes with their mood. Pediatric patients frequently reported experiencing attention challenges (50%) and difficulty concentrating (65%). Parents reported that mood shifts and becoming upset easily were the most prevalent concerns for their children. The most frequent need for services included education about MTC, treatment and research participation, and the opportunity to meet others with MTC.
Embrace the Complexity: Agnostic Evaluation of Children’s Neuropsychological Performances Reveals Hidden Neurodevelopment Patterns
Authors: Cainelli Elisa , Vedovelli Luca , Gregori Dario , Suppiej Agnese , Padalino Massimo , Cogo Paola , Bisiacchi Patrizia
Published: May 2022

The most common adverse pre/perinatal events have a great impact on neurodevelopment, with avalanche effects on academic performance, occupational status, and quality of life. Although the injury process starts early, the effects may become evident much later, when life starts to pose more challenging demands. In the present work, we want to address the impact of early insults from an evolutionary perspective by performing unsupervised cluster analysis. We fed all available data, but not the group identification, into the algorithm for 114 children aged 5–10 years, with different adverse medical conditions: healthy (n = 30), premature (n = 28), neonatal hypoxic-ischemic encephalopathy (n = 28), and congenital heart disease (n = 28). We measured general intelligence and many neuropsychological domains (language, attention, memory, executive functions, and social skills). We found three emerging groups that identify children with multiple impairments (cluster 3), children with variable neuropsychological profiles but in the normal range (cluster 2), and children with adequate profiles and good performance in IQ and executive functions (cluster 1). Our analysis divided our patients by severity levels rather than by identifying specific neuropsychological phenotypes, suggesting different developmental trajectories that are characterized by good resilience to early stressful events with adequate development or by pervasive vulnerability to neurodevelopmental disorders.
Functional Performance of Silicon with Periodic Surface Structures Induced by Femtosecond Pulsed Laser
Authors: Chen Yong , Peng Weiping , Hu Xiaofeng , Zhang Chen
Published: May 2022

A micro/nano surface structure can produce specific properties, such as super hydrophilicity, low reflectance property, etc. A femtosecond laser-induced periodic surface structure is an important manufacturing process for the micro/nano structure. This research investigated the effects of scanning intervals and laser power on the surface morphology, wetting properties, and reflectance properties of LIPSS based on a silicon wafer. The results showed that the laser power had a significant effect on the surface morphology and wettability of silicon. With the increase of laser power, the surface roughness, etching depth and surface hydrophilicity increased. However, the laser power had little effect on the surface reflectance. The scanning interval had a great influence on the wettability and reflectance property of silicon. With the decrease of the scanning interval, the surface hydrophobicity and reflectance of silicon first decrease and then remain basically stable from 10 μm.
Bullet Frangibility Factor Quantification by Using Explicit Dynamic Simulation Method
Authors: Widyastuti Widyastuti , Ramadhian Holly Indi , Hidayat Mas Irfan Purbawanto , Wibowo Adhy Prihatmiko , Ardhyananta Hosta
Published: May 2022

Frangible bullets have a unique property that disintegrates into fragments upon hitting a hard target or obstacle. This peculiar ability to become fragments after impact is called frangibility. In this study, frangibility testing was carried out theoretically via modeling using the explicit dynamics method with ANSYS Autodyn solver integrated by ANSYS Workbench software. This paper aims to analyze frangibility through two main factors: material properties and projectile design. The results show the scattering and remaining bullet fragments after impact. According to the modeling results, the frangibility factor values are 9.34 and 10.79, respectively. Based on the frangibility factor, errors based on the frangibility factor by comparing the experimental results and simulations for AMMO 1 and AMMO 2 are 10.5% and 1.09%. Based on simulation results, the AMMO 2 design bullet scattering pattern shows several scattering particles more than the AMMO 1 design, with the furthest distance scattering AMMO 1 and AMMO 2 bullets being 1.01 m and 2658 m.
First High-Resolution Crystal Structures of DNA:2′-O-Methyl-RNA Heteroduplexes
Authors: Dolot Rafał , Maciaszek Anna , Mikołajczyk Barbara , Nawrot Barbara
Published: May 2022

Heteroduplexes composed of all-DNA and all-2′-OMe RNA strands do not occur in nature, but they have found application in the development of molecular beacons and could also be used as aptamers or elements of nucleic acid-based nanostructures that will contain such structural motifs. The crystallization experiments performed have shown that the introduction of overhangs at the ends of the duplex has a great influence on the success of crystallization, as well as on the DNA:2′-OMe-RNA heteroduplex crystal packing. The molecular and crystal structure of the DNA:2′-O-methyl-RNA heteroduplex in its overhanging and blunt-ended versions was determined at 100 K using synchrotron radiation with a resolution of 1.91 and 1.55 Å, respectively. The Zn-SAD method was used to resolve the original duplex structure when molecular replacement by many existing models of duplex structures failed. Both molecules analyzed adopted a conformation close to the A-RNA double helix. The presented structures provide the first insight into this type of heteroduplexes and allowed a comparative analysis with existing nucleic acid homo- and heteroduplex structures. The results of our research expand the knowledge of the structural properties of new heteroduplexes and may be useful for future applications, such as therapies using this class of compounds.
Wind-Direction Estimation from Single X-Band Marine Radar Image Improvement by Utilizing the DWT and Azimuth-Scale Expansion Method
Authors: Yu Huanyu , Wang Hui , Lu Zhizhong
Published: May 2022

In this study, a method based on the discrete wavelet transform (DWT) and azimuth-scale expansion is presented to retrieve the sea-surface wind direction from a single X-band marine radar image. The algorithm first distinguishes rain-free and rain-contaminated radar images based on the occlusion zero-pixel percentage and then discards the rain-contaminated images. The radar image whose occlusion areas have been removed is decomposed into different low-frequency sub-images by the 2D DWT, and the appropriate low-frequency sub-image is selected. Images collected with a standard marine HH-polarized X-band radar operating at grazing incidence display a single intensity peak in the upwind direction. To overcome the influence of the occlusion area, before determining the wind direction, the data near the ship bow are shifted to expand the azimuth scale of the data. Finally, a harmonic function is least-square-fitted to the range-averaged radar return of the low-frequency sub-image as a function of the antenna look azimuth to determine the wind direction. Different from the wind-direction retrieval algorithms previously presented, this method is more suitable for sailing ships, as it functions well even if the radar data are heavily blocked. The results show that compared with the single-curve fitting algorithm, the algorithm based on DWT and azimuth-scale expansion can improve the wind-direction results in sailing ships, showing a reduction of 7.84° in the root-mean-square error with respect to the reference.