bluuebunny/crossref_metadata_2025 huggingface dataset:
Meta-Analysis of Genetic Factors for Potato Starch Phosphorylation
Authors: Khlestkin Vadim , Erst Tatyana , Igoshin Alexander , Rozanova Irina , Khlestkina Elena
Published: May 2022

Starch is one of the most demanded renewable feedstock in the world. The degree of phosphorylation of native potato (Solanum tuberosum L.) starch is a practically important quantitative trait, significantly influencing its physical and chemical properties. In this study, we evaluated the genetic diversity of the population of potato varieties and quantified phosphorus content in potato tuber starch harvested in 2017, 2018, and 2019. With the statistical methods, the most promising varieties for the next generation of breeding were identified for the first time. Genotyping and chemotyping data were utilized for genome-wide associations study (GWAS) in order to reveal genetic factors underlying the trait. GWAS based on a general linear model (GLM) with principal component analysis (PCA) was performed. The approach allowed us to identify two new, and confirm two previously found, significant SNPs on chromosome 5 associated with phosphorus content in starch. A search for the protein products coded in the genome regions carrying the significant SNPs revealed a cluster of genes that code glycoside and protein kinases, thus forming an operon-like structure. The genetic markers can be used for marker-assisted selection or to be considered as potential targets for genome editing to improve the industrially important properties of potato native starch via “intravital modification”.
Changes in the Dentition of Small Dogs up to 4 Months of Age
Authors: Lorászkó Gábor , Rácz Bence , Ózsvári László
Published: May 2022

It is common practice in EU member states to permit the entry of dogs vaccinated against rabies at the age of at least 3 months. In the absence of easily applicable comparative data, subjective disputes emerge around age. The aim of our study was to observe the development of dog teeth. During birth, an abnormally lying Yorkshire Terrier fetus was stuck in the birth canal, which led to a caesarean section, hence, the exact date of birth was known. For the next 4 months, two puppies were examined weekly, and they showed the same development. The dogs were born without teeth. At the age of 4.5 weeks, the canines I appeared, together with the adjacent incisors (i3), and the second incisor (i2) also erupted at the age of 6 weeks. A week later, a first incisor (i1) also appeared. From the age of 2.5 months, the distance between the teeth was increasing, especially on the upper dental arch. At 3.5 months of age, only the bottom front incisors (i1) had not grown in a row, and the significant distance between the top incisors, comparable to the width of the tooth, was striking. Since only two dogs of one breed were involved in this case study, the observations cannot be generalized.
Hitchhiking Mapping of Candidate Regions Associated with Fat Deposition in Iranian Thin and Fat Tail Sheep Breeds Suggests New Insights into Molecular Aspects of Fat Tail Selection
Authors: Moradi Mohammad Hossein , Nejati-Javaremi Ardeshir , Moradi-Shahrbabak Mohammad , Dodds Ken G. , Brauning Rudiger , McEwan John C.
Published: May 2022

The fat tail is a phenotype that divides indigenous Iranian sheep genetic resources into two major groups. The objective of the present study is to refine the map location of candidate regions associated with fat deposition, obtained via two separate whole genome scans contrasting thin and fat tail breeds, and to determine the nature of the selection occurring in these regions using a hitchhiking approach. Zel (thin tail) and Lori-Bakhtiari (fat tail) breed samples that had previously been run on the Illumina Ovine 50 k BeadChip, were genotyped with a denser set of SNPs in the three candidate regions using a Sequenom Mass ARRAY platform. Statistical tests were then performed using different and complementary methods based on either site frequency (FST and Median homozygosity) or haplotype (iHS and XP-EHH). The results from candidate regions on chromosome 5 and X revealed clear evidence of selection with the derived haplotypes that was consistent with selection to near fixation for the haplotypes affecting fat tail size in the fat tail breed. An analysis of the candidate region on chromosome 7 indicated that selection differentiated the beneficial alleles between breeds and homozygosity has increased in the thin tail breed which also had the ancestral haplotype. These results enabled us to confirm the signature of selection in these regions and refine the critical intervals from 113 kb, 201 kb, and 2831 kb to 28 kb, 142 kb, and 1006 kb on chromosome 5, 7, and X respectively. These regions contain several genes associated with fat metabolism or developmental processes consisting of TCF7 and PPP2CA (OAR5), PTGDR and NID2 (OAR7), AR, EBP, CACNA1F, HSD17B10,SLC35A2, BMP15, WDR13, and RBM3 (OAR X), and each of which could potentially be the actual target of selection. The study of core haplotypes alleles in our regions of interest also supported the hypothesis that the first domesticated sheep were thin tailed, and that fat tail animals were developed later. Overall, our results provide a comprehensive assessment of how and where selection has affected the patterns of variation in candidate regions associated with fat deposition in thin and fat tail sheep breeds.
Effect of Different Basal Culture Media and Sera Type Combinations on Primary Broiler Chicken Muscle Satellite Cell Heterogeneity during Proliferation and Differentiation
Authors: Flees Joshua J. , Starkey Charles W. , Starkey Jessica D.
Published: May 2022

The objective of this experiment was to access primary satellite cell (SC) proliferation and differentiation when cultured in different combinations of basal media and sera due to little consistency being published on the optimal culture media for primary broiler chicken satellite cells. Cells were cultured in one of three different basal media: McCoy’s 5A, high glucose Dulbecco’s Modified Eagle’s medium (DMEM), and low glucose DMEM. Media were supplemented with 15% chicken serum (CS) or a combination of 5% horse serum (HS) + 10% CS during proliferation while 3% HS or 3% CS were added to the media during differentiation. Cultures were immunofluorescence stained for myogenic regulatory factors (MRF) at 48, 72, and 96 h post-plating for proliferation (Pax7, MyoD, and Myf-5) and 96 h post-proliferation during differentiation (Pax7 and MyoD), including MF20 to assess fusion. Cells cultured in Dulbecco’s Modified Eagle’s medium tended to have higher proportions of myogenic cells expressing MRF during proliferation and promoted fusion into myotubes compared with McCoy’s 5A during differentiation. Culturing primary SC in low glucose media, glucose concentrations similar to circulating glucose concentrations in broilers, HSCS during proliferation and CS during differentiation, appears to be optimal for promoting broiler chicken satellite cell proliferation and differentiation.
Yeast-Derived Products: The Role of Hydrolyzed Yeast and Yeast Culture in Poultry Nutrition—A Review
Authors: Perricone Vera , Sandrini Silvia , Irshad Nida , Savoini Giovanni , Comi Marcello , Agazzi Alessandro
Published: May 2022

Yeasts are single-cell eukaryotic microorganisms that are largely employed in animal nutrition for their beneficial effects, which are owed to their cellular components and bioactive compounds, among which are mannans, β-glucans, nucleotides, mannan oligosaccharides, and others. While the employment of live yeast cells as probiotics in poultry nutrition has already been largely reviewed, less information is available on yeast-derived products, such as hydrolyzed yeast (HY) and yeast culture (YC). The aim of this review is to provide the reader with an overview of the available body of literature on HY and YC and their effects on poultry. A brief description of the main components of the yeast cell that is considered to be responsible for the beneficial effects on animals’ health is also provided. HY and YC appear to have beneficial effects on the poultry growth and production performance, as well as on the immune response and gut health. Most of the beneficial effects of HY and YC have been attributed to their ability to modulate the gut microbiota, stimulating the growth of beneficial bacteria and reducing pathogen colonization. However, there are still many areas to be investigated to better understand and disentangle the effects and mechanisms of action of HY and YC.
Antibiotics Use in Primary Care during COVID-19
Authors: Llor Carl
Published: May 2022

During national health emergencies such as the COVID-19 pandemic, a robust primary care system plays a crucial role in triaging, educating patients and testing [...]
Dissemination of OXA-48- and NDM-1-Producing Enterobacterales Isolates in an Algerian Hospital
Authors: Abderrahim Amel , Djahmi Nassima , Loucif Lotfi , Nedjai Sabrina , Chelaghma Widad , Gameci-Kirane Djamila , Dekhil Mazouz , Lavigne Jean-Philippe , Pantel Alix
Published: May 2022

Multidrug-resistant (MDR) Enterobacterales remain an increasing problem in Algeria, notably due to the emergence of carbapenemase producers. We investigated the molecular characteristics of carbapenem-resistant Enterobacterales isolates recovered from outpatients and inpatients in Eastern Algeria. Non-repetitive Enterobacterales with reduced susceptibility to carbapenems were consecutively collected from clinical specimens in Annaba University Hospital (Algeria) between April 2016 and December 2018. Isolates were characterized with regard to antibiotic resistance, resistome and virulome content, clonality, and plasmid support. Of the 168 isolates analyzed, 29 (17.3%) were carbapenemase producers and identified as K. pneumoniae (n = 23), E. coli (n = 5), and E. cloacae (n = 1). blaOXA-48 was the most prevalent carbapenemase-encoding gene (n = 26/29), followed by blaNDM-1 gene (n = 3/29). K. pneumoniae isolates harbored some virulence traits (entB, ugeF, ureA, mrkD, fimH), whereas E. coli had a commensal origin (E, A, and B1). Clonality analysis revealed clonal expansions of ST101 K. pneumoniae and ST758 E. coli. Plasmid analysis showed a large diversity of incompatibility groups, with a predominance of IncM (n = 26, 89.7%). A global dissemination of OXA-48-producing Enterobacterales in the Algerian hospital but also the detection of NDM-1-producing E. coli in community settings were observed. The importance of this diffusion must be absolutely investigated and controlled.
Myeloperoxidase and Advanced Oxidation Protein Products in the Cerebrospinal Fluid in Women and Men with Parkinson’s Disease
Authors: Fernández-Espejo Emilio , Rodríguez de Fonseca Fernando , Gavito Ana Luisa , Córdoba-Fernández Antonio , Chacón José , Martín de Pablos Ángel
Published: May 2022

Background: Myeloperoxidase (MPO) and advanced oxidation protein products, or AOPP (a type of MPO-derived chlorinated adducts), have been implicated in Parkinson´s disease (PD). Human MPO also show sex-based differences in PD. The objective was to study the relationship of MPO and AOPP in the cerebrospinal fluid (CSF) with motor features of idiopathic PD in male and female patients. Methods: MPO concentration and activity and AOPP content were measured in the CSF and serum in 34 patients and 30 controls. CSF leukocytes and the integrity of the blood-brain barrier were evaluated. Correlations of MPO and AOPP with clinical variables were examined. Results: The blood-brain barrier was intact and CSF leukocyte count was normal in all patients. CSF MPO concentration and activity were similar in the cohort of patients and controls, but CSF MPO content was significantly higher in male patients than in PD women (p = 0.0084). CSF MPO concentration correlated with disease duration in male and female patients (p < 0.01). CSF MPO concentration was significantly higher in men with disease duration ≥12 years versus the remainder of the male subjects (p < 0.01). Changes in CSF MPO in women were not significant. Serum MPO concentration and activity were significantly higher in all PD patients relative to controls (p < 0.0001). CSF MPO was not correlated with serum MPO. Serum AOPP were detected in all patients, but CSF AOPP was undetectable in 53% of patients. AOPP were not quantifiable in controls. Conclusions: CSF MPO is not a good biomarker for PD because mean CSF MPO concentration and activity are not different between the cohort of patients and controls. CSF MPO concentration positively correlated with disease duration in men and women, but CSF MPO is significantly enhanced only in male patients with disease duration longer than 12 years. It can be hypothesized that the MPO-related immune response in early-stage PD might be weak in all patients, but then the MPO-related immune response is progressively enhanced in men, not women. Since the blood-brain barrier is intact, and CSF MPO is not correlated with serum MPO, CSF myeloperoxidase would reflect MPO content in brain cells, not blood-derived cells. Finally, serum AOPP was detected in all patients, but not controls, which is consistent with the occurrence of chlorinative stress in blood serum in PD. The study of CSF AOPP as biomarker could not be assessed because the ELISA assay was hampered by its detection limit in the CSF.
Inhibition of the Peroxygenase Lytic Polysaccharide Monooxygenase by Carboxylic Acids and Amino Acids
Authors: Breslmayr Erik , Poliak Peter , Požgajčić Alen , Schindler Roman , Kracher Daniel , Oostenbrink Chris , Ludwig Roland
Published: May 2022

Lytic polysaccharide monooxygenases (LPMOs) are widely distributed in fungi, and catalyze the oxidative degradation of polysaccharides such as cellulose. Despite their name, LPMOs possess a dominant peroxygenase activity that is reflected in high turnover numbers but also causes deactivation. We report on the influence of small molecules and ions on the activity and stability of LPMO during catalysis. Turbidimetric and photometric assays were used to identify LPMO inhibitors and measure their inhibitory effect. Selected inhibitors were employed to study LPMO activity and stability during cellulose depolymerization by HPLC and turbidimetry. It was found that the fungal metabolic products oxalic acid and citric acid strongly reduce LPMO activity, but also protect the enzyme from deactivation. QM calculations showed that the copper atom in the catalytic site could be ligated by bi- or tridentate chelating compounds, which replace two water molecules. MD simulations and QM calculations show that the most likely inhibition pattern is the competition between the inhibitor and reducing agent in the oxidized Cu(II) state. A correlation between the complexation energy and the IC50 values demonstrates that small, bidentate molecules interact strongest with the catalytic site copper and could be used by the fungus as physiological effectors to regulate LPMO activity.
Nuclear and Radiological Emergencies: Biological Effects, Countermeasures and Biodosimetry
Authors: Obrador Elena , Salvador-Palmer Rosario , Villaescusa Juan I. , Gallego Eduardo , Pellicer Blanca , Estrela José M. , Montoro Alegría
Published: May 2022

Atomic and radiological crises can be caused by accidents, military activities, terrorist assaults involving atomic installations, the explosion of nuclear devices, or the utilization of concealed radiation exposure devices. Direct damage is caused when radiation interacts directly with cellular components. Indirect effects are mainly caused by the generation of reactive oxygen species due to radiolysis of water molecules. Acute and persistent oxidative stress associates to radiation-induced biological damages. Biological impacts of atomic radiation exposure can be deterministic (in a period range a posteriori of the event and because of destructive tissue/organ harm) or stochastic (irregular, for example cell mutation related pathologies and heritable infections). Potential countermeasures according to a specific scenario require considering basic issues, e.g., the type of radiation, people directly affected and first responders, range of doses received and whether the exposure or contamination has affected the total body or is partial. This review focuses on available medical countermeasures (radioprotectors, radiomitigators, radionuclide scavengers), biodosimetry (biological and biophysical techniques that can be quantitatively correlated with the magnitude of the radiation dose received), and strategies to implement the response to an accidental radiation exposure. In the case of large-scale atomic or radiological events, the most ideal choice for triage, dose assessment and victim classification, is the utilization of global biodosimetry networks, in combination with the automation of strategies based on modular platforms.
Face Recognition and Tracking Framework for Human–Robot Interaction
Authors: Khalifa Aly , Abdelrahman Ahmed A. , Strazdas Dominykas , Hintz Jan , Hempel Thorsten , Al-Hamadi Ayoub
Published: May 2022

Recently, face recognition became a key element in social cognition which is used in various applications including human–robot interaction (HRI), pedestrian identification, and surveillance systems. Deep convolutional neural networks (CNNs) have achieved notable progress in recognizing faces. However, achieving accurate and real-time face recognition is still a challenging problem, especially in unconstrained environments due to occlusion, lighting conditions, and the diversity in head poses. In this paper, we present a robust face recognition and tracking framework in unconstrained settings. We developed our framework based on lightweight CNNs for all face recognition stages, including face detection, alignment and feature extraction, to achieve higher accuracies in these challenging circumstances while maintaining the real-time capabilities required for HRI systems. To maintain the accuracy, a single-shot multi-level face localization in the wild (RetinaFace) is utilized for face detection, and additive angular margin loss (ArcFace) is employed for recognition. For further enhancement, we introduce a face tracking algorithm that combines the information from tracked faces with the recognized identity to use in the further frames. This tracking algorithm improves the overall processing time and accuracy. The proposed system performance is tested in real-time experiments applied in an HRI study. Our proposed framework achieves real-time capabilities with an average of 99%, 95%, and 97% precision, recall, and F-score respectively. In addition, we implemented our system as a modular ROS package that makes it straightforward for integration in different real-world HRI systems.
Analysis of the Interaction Effects of Shield Structure Oblique Passing under an Existing Tunnel
Authors: Ou Xun , Liu Yuanming , Li Chao , Zhou Xiaohan , Chen Qingzhi , Zhou Yuhang , Zhang Quan
Published: May 2022

The interaction mechanism between a two-lane shield tunnel and an existing tunnel during oblique underpass is a matter of widespread concern in the engineering community, and knowledge in this area remains crude. In the construction of subway tunnels in mountainous cities with huge topographical fluctuations, internal forces and deformations are inevitable in existing tunnels. To verify the applicability of existing shield construction technology and empirical parameters to the Guiyang area, a systematic and refined numerical analysis was conducted on the shield passing under the existing tunnel section of the Tao-Hua interval of Guiyang Metro Line 3. In this paper, the accuracy of the numerical simulation is verified by comparing the calculated results with the data measured in the field; the settlement pattern that appeared above the existing tunnel during the construction of the shield with slurry hardening is analyzed; the internal forces, lateral deformation, and torsional deformation of the existing tunnel caused during the excavation of the new tunnel are obtained based on the numerical simulation results; finally, the effect of the old and new tunnels on the torsional deformation and settlement of the existing tunnel under different spatial intersection angles is studied. The results show that the internal forces, lateral deformation, and surface settlement of the existing tunnel due to the diagonal underpass show obvious asymmetric characteristics. Additionally, the existing tunnel experiences local irrecoverable torsional deformation, with the maximum torsional deformation occurring at the intersection of the old and new tunnels, and the spatial intersection angle of the old and new tunnels has a great influence on the maximum settlement of the tunnel vault and arch bottom, which shows a negative correlation.
Infrared Dim and Small Target Detection Based on the Improved Tensor Nuclear Norm
Authors: Fan Xiangsuo , Wu Anqing , Chen Huajin , Huang Qingnan , Xu Zhiyong
Published: May 2022

In the face of complex scenes with strong edge contours and high levels of noise, suppressing edge contours and noise levels is challenging with infrared dim and small target detection algorithms. Many advanced algorithms suffer from high false alarm rates when facing this problem. To solve this, a new anisotropic background feature weight function based on the infrared patch tensor (IPT) model was developed in this study to characterize the background airspace difference features by effectively combining the local features with the global features to suppress the strong edge contours in the structural tensor. Secondly, to enhance the target energy in the a priori model, an improved high-order cumulative model was proposed to establish the local significance region of the target as a way to achieve energy enhancement of the significant target in the structural tensor. Finally, the energy-enhanced structural tensor was introduced into the partial sum of the sensor nuclear norm (PSTNN) model as a local feature information weight matrix; the detection results were obtained by solving the model with the help of ADMM. A series of experiments show that the algorithm in this paper achieves better detection results compared with other algorithms.
Investigation into the Effects of Roller Pressing on Hardness, Roughness and Elastic Modulus of Wooden Workpieces
Authors: Kocovic Vladimir , Dzunic Dragan , Kostic Sonja , Brzakovic Ljiljana , Tadic Branko , Prica Miljana , Vukelic Djordje
Published: May 2022

The paper investigates the effects of roller pressing on the hardness, roughness, and elastic modulus of wooden workpieces. For research purposes, a roller pressing device based on purely mechanical processing was designed and developed. Four different levels of pressing force have been applied to eight different types of wood: cherry, fir, alder, linden, beech, walnut, oak, and ash. The obtained results indicate that the proposed processing method can significantly improve the hardness, elastic modulus, and surface quality of wooden workpieces. The ash sample exhibited the largest relative increase in hardness (175.9%), while the most significant relative increase in the elastic modulus (66.73%) was measured on the linden sample. The largest relative decrease in surface roughness (54.75%) was achieved on the alder sample. For all types of wood except for fir, in which case an increase in pressing force did not produce the desired reduction of roughness, correlation coefficients indicate a strong relationship between the pressing force as an input variable and the elastic modulus, hardness, and roughness as output variables.
Research on the Intelligent Construction of the Rebar Project Based on BIM
Authors: Wang Dejiang , Hu Youyang
Published: May 2022

Rebar engineering in the construction industry lacks effective technical means and has a high processing cost and high waste rate. Under the background of intelligent construction, the centralized processing mode of steel bars in prefabricated factories realizes the automatic processing of steel bars and improves the processing efficiency of steel bars. Using the C# programming language, combined with Revit secondary development technology, the automatic generation of the rebar model and the automatic export of rebar drawing are realized, which saves time for the designers to build the model. The calculation method of the cutting length of the steel bar is analyzed in this paper, which can be used as a reference for the subsequent optimization research of steel bar cutting. The assembly position information of the steel bar was introduced into an Excel table to help realize the automatic assembly of the steel bar cage and the intelligent construction of the steel bar. Combined with mixed reality technology, project personnel can interact with the reinforced BIM model through the mixed reality device Hololens2 to guide construction remotely.
Knowledge Gap in Understanding the Steroidogenic Acute Regulatory Protein Regulation in Steroidogenesis Following Exposure to Bisphenol A and Its Analogues
Authors: Jefferi Nur Erysha Sabrina , Shamhari Asma’ ‘Afifah , Hamid Zariyantey Abd , Budin Siti Balkis , Zulkifly Adam Muhammad Zackry , Roslan Fatin Norisha , Taib Izatus Shima
Published: May 2022

The use of bisphenols has become extremely common in our daily lives. Due to the extensive toxic effects of Bisphenol A (BPA), the industry has replaced this endocrine-disrupting chemical (EDC) with its analogues, which have been proven to decrease testosterone levels via several mechanisms, including targeting the steroidogenic acute regulatory (StAR) protein. However, when exposed to BPA and its analogues, the specific mechanism that emerges to target StAR protein regulations remains uncertain. Hence, this review discusses the effects of BPA and its analogues in StAR protein regulation by targeting cAMP-PKA, PLC-PKC, EGFR-MAPK/ERK and Ca2+-Nur77. BPA and its analogues mainly lead to decreased LH in blood and increased ERK expression and Ca2+ influx, with no relationship with the StAR protein regulation in testicular steroidogenesis. Furthermore, the involvement of the cAMP-PKA, PLC-PKC, and Nur77 molecules in StAR regulation in Leydig cells exposed to BPA and its analogues remains questionable. In conclusion, although BPA and its analogues have been found to disrupt the StAR protein, the evidence in connecting the signaling pathways with the StAR regulations in testicular steroidogenesis is still lacking, and more research is needed to draw a solid conclusion.
Micro-RNAs Predict Response to Systemic Treatments in Metastatic Renal Cell Carcinoma Patients: Results from a Systematic Review of the Literature
Authors: Monti Martina , Lunardini Susanna , Magli Igino Andrea , Campi Riccardo , Primiceri Giulia , Berardinelli Francesco , Amparore Daniele , Terracciano Daniela , Lucarelli Giuseppe , Schips Luigi , Ferro Matteo , Marchioni Michele
Published: May 2022

Locally advanced or metastatic renal cell carcinomas (mRCCs) account for up to 15% of all kidney cancer diagnoses. Systemic therapies (with or without surgery) represent gold standard treatments, mostly based on tyrosine kinase inhibitors in association with immunotherapy. We provide an overview of the current knowledge of miRNAs as predictors of treatment resistance. A systematic review of the literature was carried out in January 2022 following the PICO methodology. Overall, we included seven studies—four testing plasmatic miRNAs, two exosomal miRNAs, and one urinary miRNA. A total of 789 patients were included (354 for plasmatic miRNAs, 366 for urinary miRNAs, and 69 for exosomal miRNAs). Several miRNAs were tested within the included studies, but six plasmatic (miR9-5-p¸ miR-192, miR193-3p, miR-501-3p¸ miR-221, miR-376b-3p) one urinary (miR-30a-5p), and three exosomal (miR-35-5p, miR-301a-3p, miR-1293) were associated with resistance to systemic treatments or treatment failure in mRCC patients. Results showed a fair accuracy of these biomarkers in predicting treatment resistance and overall survival. However, to date, the biomarkers tested have not been validated and their clinical uses are not recommended. Nevertheless, the literature results are encouraging; future large clinical trials are warranted to validate the effectiveness of these tools in clinical decision-making.
THz-ATR Spectroscopy Integrated with Species Recognition Based on Multi-Classifier Voting for Automated Clinical Microbial Identification
Authors: Yu Wenjing , Shi Jia , Huang Guorong , Zhou Jie , Zhan Xinyu , Guo Zekang , Tian Huiyan , Xie Fengxin , Yang Xiang , Fu Weiling
Published: May 2022

The demand for rapid and accurate identification of microorganisms is growing due to considerable importance in all areas related to public health and safety. Here, we demonstrate a rapid and label-free strategy for the identification of microorganisms by integrating terahertz-attenuated total reflection (THz-ATR) spectroscopy with an automated recognition method based on multi-classifier voting. Our results show that 13 standard microbial strains can be classified into three different groups of microorganisms (Gram-positive bacteria, Gram-negative bacteria, and fungi) by THz-ATR spectroscopy. To detect clinical microbial strains with better differentiation that accounts for their greater sample heterogeneity, an automated recognition algorithm is proposed based on multi-classifier voting. It uses three types of machine learning classifiers to identify five different groups of clinical microbial strains. The results demonstrate that common microorganisms, once time-consuming to distinguish by traditional microbial identification methods, can be rapidly and accurately recognized using THz-ATR spectra in minutes. The proposed automatic recognition method is optimized by a spectroscopic feature selection algorithm designed to identify the optimal diagnostic indicator, and the combination of different machine learning classifiers with a voting scheme. The total diagnostic accuracy reaches 80.77% (as high as 99.6% for Enterococcus faecalis) for 1123 isolates from clinical samples of sputum, blood, urine, and feces. This strategy demonstrates that THz spectroscopy integrated with an automatic recognition method based on multi-classifier voting significantly improves the accuracy of spectral analysis, thereby presenting a new method for true label-free identification of clinical microorganisms with high efficiency.
Functional Neuroimaging of Human Hypothalamus in Socioemotional Behavior: A Systematic Review
Authors: Caria Andrea , Dall’Ò Ginevra Matilde
Published: May 2022

There exist extensive animal research and lesion studies in humans demonstrating a tight association between the hypothalamus and socioemotional behavior. However, human neuroimaging literature in this direction is still rather limited. In order to reexamine the functional role of this region in regulating human social behavior, we here provided a synthesis of neuroimaging studies showing hypothalamic activation during affiliative, cooperative interactions, and in relation to ticklish laughter and humor. In addition, studies reporting involvement of the hypothalamus during aggressive and antisocial interactions were also considered. Our systematic review revealed a growing number of investigations demonstrating that the evolutionary conserved hypothalamic neural circuity is involved in multiple and diverse aspects of human socioemotional behavior. On the basis of the observed heterogeneity of hypothalamus-mediated socioemotional responses, we concluded that the hypothalamus might play an extended functional role for species survival and preservation, ranging from exploratory and approaching behaviors promoting social interactions to aggressive and avoidance responses protecting and defending the established social bonds.
Brain Tsunamis in Human High-Grade Glioma: Preliminary Observations
Authors: Colpitts Kayli , Desai Masoom J. , Kogan Michael , Shuttleworth C. William , Carlson Andrew P.
Published: May 2022

Gliomas make up nearly 40% of all central nervous system tumors, with over 50% of those being high-grade gliomas. Emerging data suggests that electrophysiologic events in the peri-tumoral region may play a role in the behavior and progression of high-grade gliomas. While seizures in the peri-tumoral zone are well described, much larger and slowly propagating waves of spreading depolarization (SD) may potentially have roles in both non-epileptic transient neurologic deficits and tumor progression. SD has only recently been observed in pre-clinical glioma models and it is not known whether these events occur clinically. We present a case of SD occurring in a human high-grade glioma using gold-standard subdural DC ECoG recordings. This finding could have meaningful implications for both clinical symptomatology and potentially for disease progression in these patients. Our observations and hypotheses are based on analogy with a large body of evidence in stroke and acute neurological injury that have recently established SD as cause of transient neurological deficits as well as a fundamental mechanism of ischemic expansion. Whether SD could represent a mechanistic target in this process to limit such progression is a high priority for further clinical investigations.
Resistance Characteristic Parameters Estimation of Hydraulic Model in Heating Networks Based on Real-Time Operation Data
Authors: Luo Peng , Wang Hao , Liu Yongxin , Du Qingting , Zhang Zhengshuai
Published: May 2022

Heating systems are essential municipal infrastructure in winter, especially in severe cold cities of China. The safety and efficiency of heating systems greatly affect building energy efficiency and indoor thermal comfort. Heating networks (HNs), playing the role of transportation, are the key parts of heating systems. In HNs, hydraulic models could be affected by the accuracy of resistance characteristic parameters, which are expressed by pipe friction parameters (PFPs) in this paper. As the uniqueness of the estimation results of PFPs has not been discussed in previous studies, this paper builds an estimation method of PFPs by dividing two types of pipes, substituting variables and establishing a split-step linearization method. Combining with the theory of matrix equations, the decision conditions and solution methods for obtaining the unique estimation results of PFPs are determined. Theoretical analysis and case study results show that estimation values of PFPs can be obtained by utilizing measured data under multiple hydraulic conditions. In the example of DN and the simple actual HN, the average estimation deviation of PFPs is 1.42% and 1.86%, which are accurate enough for actual engineering. Estimation results of PFPs obtained by this method guarantee the accuracy of analysis and regulation in heating systems and improve social energy utilization efficiency.
Associations between Smoking and Alcohol and Follicular Lymphoma Incidence and Survival: A Family-Based Case-Control Study in Australia
Authors: Odutola Michael K. , van Leeuwen Marina T. , Turner Jennifer , Bruinsma Fiona , Seymour John F. , Prince Henry M. , Milliken Samuel T. , Trotman Judith , Verner Emma , Tiley Campbell , Roncolato Fernando , Underhill Craig R. , Opat Stephen S. , Harvey Michael , Hertzberg Mark , Benke Geza , Giles Graham G. , Vajdic Claire M.
Published: May 2022

The association between smoking and alcohol consumption and follicular lymphoma (FL) incidence and clinical outcome is uncertain. We conducted a population-based family case-control study (709 cases: 490 controls) in Australia. We assessed lifetime history of smoking and recent alcohol consumption and followed-up cases (median = 83 months). We examined associations with FL risk using unconditional logistic regression and with all-cause and FL-specific mortality of cases using Cox regression. FL risk was associated with ever smoking (OR = 1.38, 95%CI = 1.08–1.74), former smoking (OR = 1.36, 95%CI = 1.05–1.77), smoking initiation before age 17 (OR = 1.47, 95%CI = 1.06–2.05), the highest categories of cigarettes smoked per day (OR = 1.44, 95%CI = 1.04–2.01), smoking duration (OR = 1.53, 95%CI = 1.07–2.18) and pack-years (OR = 1.56, 95%CI = 1.10–2.22). For never smokers, FL risk increased for those exposed indoors to >2 smokers during childhood (OR = 1.84, 95%CI = 1.11–3.04). For cases, current smoking and the highest categories of smoking duration and lifetime cigarette exposure were associated with elevated all-cause mortality. The hazard ratio for current smoking and FL-specific mortality was 2.97 (95%CI = 0.91–9.72). We found no association between recent alcohol consumption and FL risk, all-cause or FL-specific mortality. Our study showed consistent evidence of an association between smoking and increased FL risk and possibly also FL-specific mortality. Strengthening anti-smoking policies and interventions may reduce the population burden of FL.
Personalised Risk Prediction in Hereditary Breast and Ovarian Cancer: A Protocol for a Multi-Centre Randomised Controlled Trial
Authors: Archer Stephanie , Fennell Nichola , Colvin Ellen , Laquindanum Rozelle , Mills Meredith , Dennis Romy , Stutzin Donoso Francisca , Gold Rochelle , Fan Alice , Downes Kate , Ford James , Antoniou Antonis C. , Kurian Allison W. , Evans D. Gareth , Tischkowitz Marc
Published: May 2022

Women who test positive for an inherited pathogenic/likely pathogenic gene variant in BRCA1, BRCA2, PALB2, CHEK2 and ATM are at an increased risk of developing certain types of cancer—specifically breast (all) and epithelial ovarian cancer (only BRCA1, BRCA2, PALB2). Women receive broad cancer risk figures that are not personalised (e.g., 44–63% lifetime risk of breast cancer for those with PALB2). Broad, non-personalised risk estimates may be problematic for women when they are considering how to manage their risk. Multifactorial-risk-prediction tools have the potential to deliver personalised risk estimates. These may be useful in the patient’s decision-making process and impact uptake of risk-management options. This randomised control trial (registration number to follow), based in genetic centres in the UK and US, will randomise participants on a 1:1 basis to either receive conventional cancer risk estimates, as per routine clinical practice, or to receive a personalised risk estimate. This personalised risk estimate will be calculated using the CanRisk risk prediction tool, which combines the patient’s genetic result, family history and polygenic risk score (PRS), along with hormonal and lifestyle factors. Women’s decision-making around risk management will be monitored using questionnaires, completed at baseline (pre-appointment) and follow-up (one, three and twelve months after receiving their risk assessment). The primary outcome for this study is the type and timing of risk management options (surveillance, chemoprevention, surgery) taken up over the course of the study (i.e., 12 months). The type of risk-management options planned to be taken up in the future (i.e., beyond the end of the study) and the potential impact of personalised risk estimates on women’s psychosocial health will be collected as secondary-outcome measures. This study will also assess the acceptability, feasibility and cost-effectiveness of using personalised risk estimates in clinical care.
Treatment Approaches and Outcome of Patients with Neuroendocrine Neoplasia Grade 3 in German Real-World Clinical Practice
Authors: Luecke Simone , Fottner Christian , Lahner Harald , Jann Henning , Zolnowski Dominik , Quietzsch Detlef , Grabowski Patricia , Cremer Birgit , Maasberg Sebastian , Pape Ulrich-Frank , Mueller Hans-Helge , Gress Thomas Matthias , Rinke Anja ,   the members of the German NET Registry
Published: May 2022

Background: Neuroendocrine neoplasia grade 3 (NEN G3) represents a rare and heterogeneous cancer type with a poor prognosis. The aim of our study was to analyze real-world data from the German NET Registry with a focus on therapeutic and prognostic aspects. Methods: NEN G3 patients were identified within the German NET Registry. Demographic data and data on treatments and outcomes were retrieved. Univariate analyses were performed using the Kaplan–Meier-method. Multivariate analysis was performed using a Cox proportional hazard model. Results: Of 445 included patients, 318 (71.5%) were diagnosed at stage IV. Well-differentiated morphology (NET G3) was described in 31.7%, 60% of cases were classified as neuroendocrine carcinoma (NEC), and the median Ki67 value was 50%. First-line treatment comprised chemotherapy in 43.8%, with differences in the choice of regimen with regard to NET or NEC, and surgery in 41.6% of patients. Median overall survival for the entire cohort was 31 months. Stage, performance status and Ki67 were significant prognostic factors in multivariate analysis. Conclusions: The survival data of our national registry compare favorably to population-based data, probably mainly because of a relatively low median Ki67 of 50%. Nevertheless, the best first- and second-line approaches for specific subgroups remain unclear, and an international effort to fill these gaps is needed.
Impact of Insulin Therapies on Cancer Incidence in Type 1 and Type 2 Diabetes: A Population-Based Cohort Study in Reggio Emilia, Italy
Authors: Vicentini Massimo , Ballotari Paola , Venturelli Francesco , Ottone Marta , Manicardi Valeria , Gallo Marco , Greci Marina , Pinotti Mirco , Pezzarossi Annamaria , Giorgi Rossi Paolo
Published: May 2022

Objective: To assess the effect of insulin on cancer incidence in type 1 (T1DM) and type 2 diabetes (T2DM). Methods: The cohort included all 401,172 resident population aged 20–84 in December 2009 and still alive on December 2011, classified for DM status. Drug exposure was assessed for 2009–2011 and follow up was conducted from 2012 to 2016 through the cancer registry. Incidence rate ratios (IRRs) were computed for all sites and for the most frequent cancer sites. Results: among residents, 21,190 people had diabetes, 2282 of whom were taking insulin; 1689 cancers occurred, 180 among insulin users. The risk for all site was slightly higher in people with T2DM compared to people without DM (IRR 1.21, 95% CI 1.14–1.27), with no excess for T1DM (IRR 0.73, 95% CI 0.45–1.19). The excess in T2DM remained when comparing with diet-only treatment. In T2DM, excess incidence was observed for liver and pancreas and for NETs: 1.76 (95% CI 1.44–2.17) and 1.37 (95% CI 0.99–1.73), respectively. For bladder, there was an excess both in T1DM (IRR 3.00, 95% CI 1.12, 8.02) and in T2DM (IRR1.27, 95% CI 1.07–1.50). Conclusions: Insulin was associated with a 20% increase in cancer incidence. The risk was higher for liver, pancreatic, bladder and neuroendocrine tumours.
Photodynamic Therapy in Combination with the Hepatitis B Core Virus-like Particles (HBc VLPs) to Prime Anticancer Immunity for Colorectal Cancer Treatment
Authors: Hao Yang , Gu Zili , Yu Zhenfeng , Schomann Timo , Sayedipour Sana , Aguilar Julio C. , ten Dijke Peter , Cruz Luis J.
Published: May 2022

Photodynamic therapy (PDT), which combines light and oxygen with a photosensitizer to induce reactive oxygen species (ROS)-mediated killing of primary tumor cells, benefits from non-invasive properties and its negligible toxicity to surrounding healthy tissues. In this study, we have shown that the second-generation photosensitizer FOSCAN can be internalized by tumor cells and effectively induce tumor cell death when exposed to laser irradiation in vitro. In addition, these dying tumor cells can be phagocytosed by dendritic cells and lead to their activation and maturation as assessed by in vitro co-culture models. While PDT induces immunogenic tumor cell apoptosis, its application for the treatment of tumors located in deep tissues and advanced malignancies has been limited. In this study, we demonstrate that hepatitis B core virus-like particles (HBc VLPs) can serve as a vaccine to enhance PDT-induced anti-cancer immunity by priming humoral immune responses and inducing CD8+ T cell responses. The combination of PDT and HBc VLPs increased the survival rate of MC-38 tumor-bearing mice to 55%, compared to 33% in PDT alone and no tumor-free mice in vaccine alone. Moreover, the combination effectively prevented tumor recurrence in vivo through enhanced immune memory T cells after therapy. Therefore, as both are clinically approved techniques, this combination provides a promising strategy for cancer therapy.
Gamma Irradiation Triggers Immune Escape in Glioma-Propagating Cells
Authors: Hoppmann Nicola , Heinig Nora , Distler Ute , Kim Ella , Lennerz Volker , Krauß Yvonne , Schumann Ulrike , Giese Alf , Tenzer Stefan , Bitar Lynn , Schmidt Mirko H. H.
Published: May 2022

Glioblastoma multiforme is the most common and devastating form of brain tumor for which only palliative radio- and chemotherapy exists. Although some clinical studies on vaccination approaches have shown promising efficacy due to their potential to generate long-term immune surveillance against cancer cells, the evasion mechanisms preventing therapy response are largely uncharacterized. Here, we studied the response of glioblastoma-propagating cells (GPCs) to clinically relevant doses of γ radiation. GPCs were treated with 2.5 Gy of γ radiation in seven consecutive cellular passages to select for GPCs with increased colony-forming properties and intrinsic or radiation-induced resistance (rsGPCs). Quantitative proteomic analysis of the cellular signaling platforms of the detergent-resistant membranes (lipid rafts) in GPCs vs. rsGPCs revealed a downregulation of the MHC class I antigen-processing and -presentation machinery. Importantly, the radio-selected GPCs showed reduced susceptibility towards cytotoxic CD8+ T-cell-mediated killing. While previous studies suggested that high-dose irradiation results in enhanced antigen presentation, we demonstrated that clinically relevant sub-lethal fractionated irradiation results in reduced expression of components of the MHC class I antigen-processing and -presentation pathway leading to immune escape.
CAR-T Cells Shoot for New Targets: Novel Approaches to Boost Adoptive Cell Therapy for B Cell-Derived Malignancies
Authors: Marhelava Katsiaryna , Krawczyk Marta , Firczuk Malgorzata , Fidyt Klaudyna
Published: May 2022

Chimeric antigen receptor (CAR)-T cell therapy is undeniably a promising tool in combating various types of hematological malignancies. However, it is not yet optimal and a significant number of patients experience a lack of response or relapse after the treatment. Therapy improvement requires careful analysis of the occurring problems and a deeper understanding of the reasons that stand behind them. In this review, we summarize the recent knowledge about CAR-T products’ clinical performance and discuss diversified approaches taken to improve the major shortcomings of this therapy. Especially, we prioritize the challenges faced by CD19 CAR-T cell-based treatment of B cell-derived malignancies and revise the latest insights about mechanisms mediating therapy resistance. Since the loss of CD19 is one of the major obstacles to the success of CAR-T cell therapy, we present antigens that could be alternatively used for the treatment of various types of B cell-derived cancers.