bluuebunny/crossref_metadata_2025 huggingface dataset:
Impact of a Regulation Restricting Critical Antimicrobial Usage on Prevalence of Antimicrobial Resistance in Escherichia coli Isolates From Fecal and Manure Pit Samples on Dairy Farms in Québec, Canada
Authors: de Lagarde Maud , Fairbrother John M. , Archambault Marie , Dufour Simon , Francoz David , Massé Jonathan , Lardé Hélène , Aenishaenslin Cécile , Paradis Marie-Ève , Roy Jean-Philippe
Published: February 2022

To tackle antimicrobial resistance (AMR), one of the major health threats of this century, the World Health Organization (WHO) endorsed a global action plan in 2015. This plan calls countries to develop national actions to address AMR. The province of Québec, Canada, adopted a new regulation on the 25thof February 2019, to limit the use in food animals of antimicrobials of very high importance in human medicine. We aimed to establish the impact of this regulation by comparing the AMR situation in dairy cattle in Québec ~2 years before and 2 years after its introduction. We sampled calves, cows, and the manure pit in 87 farms. Generic and putative ESBL/AmpCE. coliwere tested for susceptibility to 20 antimicrobials. Logistic regression was used to investigate whether the probability of antimicrobial resistance differed between isolates obtained from the pre and post regulation periods by sample type (calves, cows, manure pit) and in general. To identify AMR genes dissemination mechanisms, we sequenced the whole genome of 15 generic isolates. In the generic collection, at the herd level, the proportion of multidrug resistant (MDR) isolates, decreased significantly from 83 to 71% (p= 0.05). Folate inhibitor and aminoglycoside resistances demonstrated a significant decrease. However, when analyzed by sample type (calves, cows, manure pit), we did not observe a significant AMR decrease in any of these categories. In the ESBL/AmpC collection, we did not detect any significant difference between the two periods. Also, the general resistance gene profile was similar pre and post regulation. We identified both clonal and plasmidic dissemination of resistance genes. In conclusion, as early as 2 years post regulation implementation, we observed a significant decrease in MDR in the dairy industry in Quebec in the genericE. colicollection with folate inhibitor and aminoglycoside resistances showing the most significant decrease. No other significant decreases were yet observed.
Infrastructure and Subjective Well-Being from a Gender Perspective
Authors: Alarcón-García Gloria , Buendía-Azorín José Daniel , Sánchez-de-la-Vega María del Mar
Published: February 2022

Mainstreaming gender analysis into all aspects of policy making, including infrastructure and economic policy, is a key aspect to achieving gender equality. The main objective of this paper is to examine the impact of several public infrastructures on well-being by gender, applying the Capability and Subjective Well-being approaches. An index of access to infrastructure is constructed and its effect on well-being is estimated using a new survey dataset from Spain. The results from the logistic regression model show that access to infrastructure positively affects subjective well-being, particularly of female respondents. All dimensions of infrastructure matter more for women’s well-being than men’s. Important differences in the impact on well-being by the types of infrastructures analyzed and the impact differs significantly by age are obtained. The findings suggest that designing public infrastructure policies can contribute to reducing gender well-being gap.
Diagnostic Performance of PD-L1 versus PD-1 Expression in Circulating CD20 Cells in Diffuse Large B-Cell Lymphoma
Authors: Saber Manal Mohamed
Published: February 2022

This study aimed to investigate PD-L1 and PD-1 expression in circulating CD20+ cells in diffuse larger B-cell lymphoma (DLBCL) and to evaluate the predictive and diagnostic performance of PD-L1 versus PD-1 expression in circulating CD20+ cells in DLBCL. Percentages of CD20+, PD-L1+CD20+, and PD-1+CD20+ cells were measured by flow cytometry in 40 DLBCL blood samples and 19 healthy controls. The DLBCL patient group was subdivided into 20 newly diagnosed patients with no treatment yet and 20 patients that had finished six cycles of CHOP therapy. Percentages of PD-L1+CD20+ and PD-1+CD20+ cells were highly significantly increased in pre-therapy patients in comparison to healthy volunteers (p < 0.001). Meanwhile, a significant decrease in percentages of PD-L1+CD20+ and PD-1+CD20+ was observed in post-CHOP therapy patients in comparison to pre-therapy patients (p < 0.001). PD-L1+CD20+ cells were significantly decreased in post-therapy patients when compared to normal controls (p < 0.001), while not for PD-1+CD20+ cells. A strong significant positive correlation between percentages of PD-L1+CD20+ and PD-1+CD20+ was detected in DLBCL patients (p < 0.001). In the pre-therapy group, high PD-L1+CD20+ and PD-1+CD20+ percentages were correlated with serum LDH levels (p = 0.021, p < 0.001). High percentages of PD-1+CD20+ were found in DLBCL patients with splenomegaly (p = 0.027). The results revealed that patients with advanced tumor stages, poor ECOG performance, and non-GCB DLBCL type had increased percentages of PD-L1+CD20+ and PD-1+CD20+ cells. Moreover, PD-L1+CD20+ % and PD-1+CD20+ % were significantly increased in DLBCL patients with bone marrow involvement or B symptoms. The superiority of PD-L1+CD20+ over PD-1+CD20+ was more profound in DLBCL prediction [AUC: 1.0] and in discriminating newly diagnosed patients [AUC: 1.0]. The findings suggest that increased PD-L1/PD-1 expression in peripheral CD20 cells may serve as a companion diagnostic marker for DLBCL. Moreover, percentages of PD-L1+CD20+ cells have better diagnostic performance with higher sensitivity and specificity than PD-1+CD20+ %.
Black Fungi and Stone Heritage Conservation: Ecological and Metabolic Assays for Evaluating Colonization Potential and Responses to Traditional Biocides
Authors: Isola Daniela , Bartoli Flavia , Meloni Paola , Caneva Giulia , Zucconi Laura
Published: February 2022

Identifying species involved in biodeterioration processes is helpful, however further effort is needed to assess their ecological requirements and actual activity. Black fungi (BF) represent one of the most underestimated threats to stone cultural heritage in the Mediterranean basin; they are difficult to kill or remove due to their ability to grow inside the rock and cope with several stresses. Despite this, little is known about BF and factors favoring their growth on stone surfaces. Eighteen BF species were here investigated for temperature and salt tolerance, and metabolic traits by plate assays. The relation between some highly damaged monuments and their BF settlers was assessed using X-ray diffraction analysis, mercury intrusion porosimetry, and SEM. The sensitiveness to four commonly used traditional biocides was also tested. All strains were able to grow within the range of 5–25 °C and in the presence of 3.5% NaCl. Instrumental analyses were fundamental in discovering the relation between halophilic strains and weathered marble sculptures. The acid, cellulase, esterase, and protease production recorded proved BF’s potential to produce a chemical action on carbonate stones and likely affect other materials/historical artefacts. Besides, the use of carboxymethylcellulose and Tween 20 should be evaluated in restoration practice to prevent tertiary bioreceptivity. Agar diffusion tests helped identify the most resistant species to biocides, opening the perspective of its use as reference organisms in material testing procedures.
A Comprehensive and Effective Framework for Traffic Congestion Problem Based on the Integration of IoT and Data Analytics
Authors: Alsaawy Yazed , Alkhodre Ahmad , Abi Sen Adnan , Alshanqiti Abdullah , Bhat Wasim Ahmad , Bahbouh Nour Mahmoud
Published: February 2022

Traffic congestion is still a challenge faced by most countries of the world. However, it can be solved most effectively by integrating modern technologies such as Internet of Things (IoT), fog computing, cloud computing, data analytics, and so on, into a framework that exploits the strengths of these technologies to address specific problems faced in traffic management. Unfortunately, no such framework that addresses the reliability, flexibility, and efficiency issues of smart-traffic management exists. Therefore, this paper proposes a comprehensive framework to achieve a reliable, flexible, and efficient solution for the problem of traffic congestion. The proposed framework has four layers. The first layer, namely, the sensing layer, uses multiple data sources to ensure a reliable and accurate measurement of the traffic status of the streets, and forwards these data to the second layer. The second layer, namely, the fog layer, consumes these data to make efficient decisions and also forwards them to the third layer. The third layer, the cloud layer, permanently stores these data for analytics and knowledge discoveries. Finally, the fourth layer, the services layer, provides assistant services for traffic management. We also discuss the functional model of the framework and the technologies that can be used at each level of the model. We propose a smart-traffic light algorithm at level 1 for the efficient management of congestion at intersections, tweet-classification and image-processing algorithms at level 2 for reliable and accurate decision-making, and support services at level 4 of the functional model. We also evaluated the proposed smart-traffic light algorithm for its efficiency, and the tweet classification and image-processing algorithms for their accuracy.
Application of Frequency Response Analysis Method to Detect Short-Circuit Faults in Three-Phase Induction Motors
Authors: Al-Ameri Salem Mgammal , Alawady Ahmed Allawy , Yousof Mohd Fairouz Mohd , Kamarudin Muhammad Saufi , Salem Ali Ahmed , Abu-Siada Ahmed , Mosaad Mohamed I.
Published: February 2022

The industry has widely accepted Frequency Response Analysis (FRA) as a reliable method to detect power transformers mechanical deformations. While the FRA technique has been recommended in recent literature as a potential diagnostic method to detect internal faults within rotating machines, detailed feasibility studies have not been fully addressed yet. This paper investigates the feasibility of using the FRA technique to detect several short circuit faults in the stator winding of three-phase induction motors (TPIMs). In this regard, FRA testing is conducted on two sets of induction motors with various short circuit faults. Investigated faults include short circuits between two phases, short circuit turns within the same phase, phase-to-ground, and phase-to-neutral short circuit. The measured FRA signatures are divided into three frequency ranges: low, medium, and high. Several statistical indicators are employed to quantify the variation between faulty and healthy signatures in each frequency range. Experimental results attest the feasibility of the FRA technique as a diagnostic tool to detect internal faults in rotating machines, such as induction motors.
Characterization of Deburring by Abrasive Flow Machining for AL6061
Authors: Kim Kwang-Joon , Kim Young-Gwan , Kim Kwon-Hee
Published: February 2022

Burrs form due to the plastic deformation of materials during machining processes, such as milling and drilling. Deburring can be very difficult when the burrs are not easily accessible for removal. In this study, abrasive flow machining (AFM) was adopted for deburring the edges of milling specimens. Based on the experimental observations on AL6061 specimens, the deburring performance was characterized in terms of flow speed, the local curvature of the streamline near the burr edge, and shear stress. A new objective function that can predict the extent of deburring is proposed based on these characteristics and validated through milling burr edge erosion tests by abrasive flow. Based on the assumption that the flow component is tangential to the burr edge has relatively little contribution to the edge erosion, an attempt was made for the application of the new objective function to the three-dimensional burr edge formed by two intersecting holes drilled with offset. The deburring test results and predictions from three-dimensional computational fluid dynamics’ (CFD) simulations were in reasonable agreement.
Validation of a Simulink Model for Simulating the Two Typical Controlled Ventilation Modes of Intensive Care Units Mechanical Ventilators
Authors: Tamburrano Paolo , Sciatti Francesco , Distaso Elia , Di Lorenzo Luigi , Amirante Riccardo
Published: February 2022

Mechanical ventilators are vital components of critical care services for patients with severe acute respiratory failure. In particular, pressure- and volume-controlled mechanical ventilation systems are the typical modes used in intensive care units (ICUs) to ventilate patients who cannot breathe adequately on their own. In this paper, a Simulink model is proposed to simulate these two typical modes employed in intensive care lung ventilators. Firstly, these two modes of ventilation are described in detail in the present paper. Secondly, the suggested Simulink model is analysed: it consists of using well-established subroutines already present in Simulink through the Simscape Fluids (gas) library, to simulate all the pneumatic components employed in some commercial ICU ventilators, such as pressure reducing valves, pressure relief valves, check valves, tanks, ON\OFF and proportional directional valves, etc. Finally, the simulation results of both modes in terms of pressure, tidal volume, and inspired/expired flow are compared with the real-life quantitative trends taken from previously recorded real-life experiments in order to validate the Simulink model. The accuracy of the model is high, as the numerical predictions are in good agreement with the real-life data, the percentage error being less than 10% in most comparisons. In this way, the model can easily be used by manufacturers and start-ups in order to produce new mechanical ventilators in the shortest time possible. Moreover, it can also be used by doctors and trainees to evaluate how the mechanical ventilator responds to different patients.
Ambient Light Energy Harvesting and Numerical Modeling of Non-Linear Phenomena
Authors: Jabbar Hamid , Jeong Taikyeong
Published: February 2022

Ambient light is an energy-harvesting source that can recharge a battery with less human interaction and can be used to prolong the operational time of the Internet of Things, e.g., mobile phones and wearable devices. Available light energy is insufficient for directly charging mobile phones and wearable devices, but it can supplement batteries to power some low-energy-consuming critical functions of the wearable device, especially in low-power consumption wearables. However, in an emergency scenario when the battery’s operational time is not sufficient or a battery charging source is unavailable, a solution is required to extend the limited battery span for mobile and wearable devices. This work presents the bottlenecks and new advancements in the commercialization of photovoltaics for smartphones and wearable technologies based on ambient light energy harvesting. A new technique, in which a smartphone cover is used as a solar concentrator to enhance light energy harvesting associated with algorithms, is experimentally demonstrated. Our research outcomes show that solar concentrators can improve light intensity by approximately 1.85 and 1.43 times at 90° and 71° angles, respectively, thus harvesting more ambient light energy at 2500 lx light intensity in a typical office environment. Type-1 PV and Type-2 PV cells were able to charge the additional battery in 8 h under 2500 lx lighting intensity in an indoor office environment. A system and logic algorithm technique is presented to efficiently transfer harvested light energy to perform low-energy consumption operations in a device, in order to improve the operational time of the device’s battery.
A Multipurpose Wearable Sensor-Based System for Weight Training
Authors: Balkhi Parinaz , Moallem Mehrdad
Published: February 2022

In recent years, there has been growing interest in automated tracking and detection of sports activities. Researchers have shown that providing activity information to individuals during their exercise routines can greatly help them in achieving their exercise goals. In particular, such information would help them to maximize workout efficiency and prevent overreaching and overtraining. This paper presents the development of a novel multipurpose wearable device for automatic weight detection, activity type recognition, and count repetition in sports activities such as weight training. The device monitors weights and activities by using an inertial measurement unit (IMU), an accelerometer, and three force sensors mounted in a glove, and classifies them by utilizing developed machine learning models. For weight detection purposes, different classifiers including Linear Discriminant Analysis (LDA), Support Vector Machine (SVM), and Multi-layer Perceptron Neural Networks (MLP) were investigated. For activity recognition, the K nearest neighbor (KNN), Decision Tree (DT), Random Forest (RF), and SVM models were trained and examined. Experimental results indicate that the SVM classifier can achieve the highest accuracy for weight detection whereas RF can outperform other classifiers for activity recognition. The results indicate feasibility of developing a wearable device that can provide in-situ accurate information regarding the lifted weight and activity type with minimum physical intervention.
Multielectrode Arrays for Functional Phenotyping of Neurons from Induced Pluripotent Stem Cell Models of Neurodevelopmental Disorders
Authors: McCready Fraser P. , Gordillo-Sampedro Sara , Pradeepan Kartik , Martinez-Trujillo Julio , Ellis James
Published: February 2022

In vitro multielectrode array (MEA) systems are increasingly used as higher-throughput platforms for functional phenotyping studies of neurons in induced pluripotent stem cell (iPSC) disease models. While MEA systems generate large amounts of spatiotemporal activity data from networks of iPSC-derived neurons, the downstream analysis and interpretation of such high-dimensional data often pose a significant challenge to researchers. In this review, we examine how MEA technology is currently deployed in iPSC modeling studies of neurodevelopmental disorders. We first highlight the strengths of in vitro MEA technology by reviewing the history of its development and the original scientific questions MEAs were intended to answer. Methods of generating patient iPSC-derived neurons and astrocytes for MEA co-cultures are summarized. We then discuss challenges associated with MEA data analysis in a disease modeling context, and present novel computational methods used to better interpret network phenotyping data. We end by suggesting best practices for presenting MEA data in research publications, and propose that the creation of a public MEA data repository to enable collaborative data sharing would be of great benefit to the iPSC disease modeling community.
Rewilding by Wolf Recolonisation, Consequences for Ungulate Populations and Game Hunting
Authors: Rodríguez-Recio Mariano , Wikenros Camilla , Zimmermann Barbara , Sand Håkan
Published: February 2022

The ongoing recolonisations of human-transformed environments in Europe by large carnivores like the wolf Canis lupus means that conservation conflicts could re-surface, among other reasons, due to predation on ungulate game species. We estimated the effect of wolves on ungulate species using data on wolf prey selection, kill rates and territory size to build a hypothetical case of future expansion. We extrapolated results on predation from the current wolf distribution in central Sweden and eastern Poland to the eventual wolf recolonisation of southern Sweden. We then calculated the proportion of five ungulate game species killed annually by wolves, and the ratio between the predicted annual predation by wolves given future colonization and the number of ungulates currently harvested by hunters. Results showed that wolf recolonization in southern Sweden would have a minor impact on the estimated population densities of red deer Cervus elaphus, fallow deer Dama dama and wild boar Sus scrofa, but is likely to lead to a significant reduction in human captures of moose Alces alces and roe deer Capreolus capreolus. The current five-ungulate species system in southern Sweden suggests a potential for two to four times higher wolf density than the two-ungulate species system in the northern part of their current distribution. Management and conservation of recolonizing large carnivores require a better understanding of the observed impact on game populations under similar ecological conditions to ameliorate conservation conflicts and achieve a paradigm of coexistence. Integrating these predictions into management is paramount to the current rewilding trend occurring in many areas of Europe or North America.
Relationship between Peak Inspiratory Flow and Patient and Disease Characteristics in Individuals with COPD—A Systematic Scoping Review
Authors: Leving Marika T. , Kocks Janwillem , Bosnic-Anticevich Sinthia , Dekhuijzen Richard , Usmani Omar S.
Published: February 2022

Optimal delivery of medication via dry powder inhalers, the most commonly prescribed inhaler type, is dependent on a patient achieving a minimum level of inspiratory flow during inhalation. However, measurement of peak inspiratory flow (PIF) against the simulated resistance of a dry powder inhaler is not frequently performed in clinical practice due to time or equipment limitations. Therefore, defining which patient characteristics are associated with lower PIF is critically important to help clinicians optimize their inhaler choice through a more personalized approach to prescribing. The objective of this scoping review was to systematically evaluate patient and disease characteristics determining PIF in patients with chronic obstructive pulmonary disease (COPD). Medline, Cochrane and Embase databases were systematically searched for relevant studies on PIF in patients with COPD published in English between January 2000 and May 2021. The quality of evidence was assessed using a modified Grading of Recommendations Assessment, Development and Evaluation checklist. Of 3382 citations retrieved, 35 publications were included in the review (nine scored as high quality, 13 as moderate, nine as low, and four as very low). Factors correlating with PIF in >70% of papers included both patient characteristics (lower PIF correlated with increased age, female gender, shorter height, decreased handgrip and inspiratory muscle strength, and certain comorbidities) and disease characteristics (lower PIF correlated with markers of lung hyperinflation, lower peak expiratory flow [PEF] and increased disease severity). Other factors correlating with adequate/optimal or improved PIF included education/counseling and exercise/inspiratory muscle training; impaired physical function and errors in inhalation technique/non-adherence were associated with low/suboptimal PIF. In conclusion, clinicians should measure PIF against the simulated resistance of a particular device wherever possible. However, as this often cannot be done due to lack of resources or time, the patient and disease characteristics that influence PIF, as identified in this review, can help clinicians to choose the most appropriate inhaler type for their patients.
Cholesterol Significantly Affects the Interactions between Pirfenidone and DPPC Liposomes: Spectroscopic Studies
Authors: Le-Deygen Irina M. , Safronova Anastasia S. , Mamaeva Polina V. , Skuredina Anna A. , Kudryashova Elena V.
Published: February 2022

In this work, we studied the effect of as on the interaction of membrane DPPC with the key antifibrotic drug pirfenidone. Liposomal forms of pirfenidone were obtained using passive loading. The addition of cholesterol reduces the loading efficiency of pirfenidone by 10%. The main binding site of pirfenidone in DPPC liposomes is the carbonyl group: the interaction with PF significantly increases the proportion of low-hydrated carbonyl groups as revealed by ATR-FTIR spectroscopy. The phosphate group acts as an additional binding site; however, due to shielding by the choline group, this interaction is weak. The hydrophobic part of the bilayer is not involved in PF binding at room temperature. Cholesterol changes the way of interaction between carbonyl groups and pirfenidone probably because of the formation of two subpopulations of DPPC and causes a dramatic redistribution of carbonyl groups onto the degrees of hydration. The proportion of moderately hydrated carbonyl groups increases, apparently due to the deepening of pirfenidone into the circumpolar region of the bilayer. For the first time, a change in the microenvironment of pirfenidone upon binding to liposomes was shown: aromatic moiety interacts with the bilayer.
A Recombinase-Based Genetic Circuit for Heavy Metal Monitoring
Authors: Akboğa Doğuş , Saltepe Behide , Bozkurt Eray Ulaş , Şeker Urartu Özgür Şafak
Published: February 2022

Rapid progress in the genetic circuit design enabled whole-cell biosensors (WCBs) to become prominent in detecting an extensive range of analytes with promise in many fields, from medical diagnostics to environmental toxicity assessment. However, several drawbacks, such as high background signal or low precision, limit WCBs to transfer from proof-of-concept studies to real-world applications, particularly for heavy metal toxicity monitoring. For an alternative WCB module design, we utilized Bxb1 recombinase that provides tight control as a switch to increase dose-response behavior concerning leakiness. The modularity of Bxb1 recombinase recognition elements allowed us to combine an engineered semi-specific heat shock response (HSR) promoter, sensitive to stress conditions including toxic ions such as cadmium, with cadmium resistance regulatory elements; a cadmium-responsive transcription factor and its cognitive promoter. We optimized the conditions for the recombinase-based cadmium biosensor to obtain increased fold change and shorter response time. This system can be expanded for various heavy metals to make an all-in-one type of WCB, even using semi-specific parts of a sensing system.
Academic User View: Organ-on-a-Chip Technology
Authors: Busek Mathias , Aizenshtadt Aleksandra , Amirola-Martinez Mikel , Delon Ludivine , Krauss Stefan
Published: February 2022

Organ-on-a-Chip (OoC) systems bring together cell biology, engineering, and material science for creating systems that recapitulate the in vivo microenvironment of tissues and organs. The versatility of OoC systems enables in vitro models for studying physiological processes, drug development, and testing in both academia and industry. This paper evaluates current platforms from the academic end-user perspective, elaborating on usability, complexity, and robustness. We surveyed 187 peers in 35 countries and grouped the responses according to preliminary knowledge and the source of the OoC systems that are used. The survey clearly shows that current commercial OoC platforms provide a substantial level of robustness and usability—which is also indicated by an increasing adaptation of the pharmaceutical industry—but a lack of complexity can challenge their use as a predictive platform. Self-made systems, on the other hand, are less robust and standardized but provide the opportunity to develop customized and more complex models, which are often needed for human disease modeling. This perspective serves as a guide for researchers in the OoC field and encourages the development of next-generation OoCs.
Fire Emergency Evacuation from a School Building Using an Evolutionary Virtual Reality Platform
Authors: Lorusso Paola , De Iuliis Melissa , Marasco Sebastiano , Domaneschi Marco , Cimellaro Gian Paolo , Villa Valentina
Published: February 2022

In the last few years, modern technologies such as numerical simulations, virtual and augmented reality, and agent-based models represented effective tools to study phenomena, which may not be experimentally reproduced due to costs, inherent hazards, or other constraints (e.g., fire or earthquake emergencies and evacuation from buildings). This paper shows how to integrate a virtual reality platform with numerical simulation tools to reproduce an evolutionary fire emergency scenario. It is computed in real time based on the building information model and a fluid dynamic software. A specific software was also used to simulate in real time the crowd dynamic in the virtual environment during the emergency evacuation process. To demonstrate the applicability of the proposed methodology, the emergency fire evacuation process for an existing school building is presented. The results show that the proposed virtual reality-based system can be employed for reproducing fire emergency scenarios. It can be used to help decision-makers to determine emergency plans and to help firefighters as a training tool to simulate emergency evacuation actions.
Incidence and Risk Factors for Venous Thromboembolism in Female Patients Undergoing Breast Surgery
Authors: Londero Ambrogio P. , Bertozzi Serena , Cedolini Carla , Neri Silvia , Bulfoni Michela , Orsaria Maria , Mariuzzi Laura , Uzzau Alessandro , Risaliti Andrea , Barillari Giovanni
Published: February 2022

Albeit it does not have the highest venous thromboembolism (VTE) incidence compared to other neoplasms, breast cancer contributes to many VTE events because it is the most diagnosed tumor in women. We aim to analyze the occurrence and timing of VTE during the follow-up of patients who underwent breast surgery, the possible correlated factors, and the overall survival. This retrospective study included all female patients diagnosed with mammary pathology and surgically treated in our clinic between January 2002 and January 2012. Of 5039 women who underwent breast surgery, 1056 were found to have no evidence of malignancy, whereas 3983 were diagnosed with breast cancer. VTE rate resulted significantly higher in patients with invasive breast cancer than in women with benign breast disease or carcinoma in situ. Invasive cancers other than lobular or ductal were associated with a higher VTE rate. In addition, chronic hypertension, high BMI, cancer type, and evidence of metastasis turned out to be the most significant risk factors for VTE in women who underwent breast surgery. Moreover, VTE occurrence significantly impacted survival in invasive breast cancer patients. Compared to women with benign mammary pathology, VTE prevalence in women with breast cancer is significantly higher. The knowledge about the risk factors of VTE could be helpful as prognostic information, but also to eventually target preventive treatment strategies for VTE, as far as the co-existence of invasive breast cancer and VTE has a significantly negative impact on survival.
Expression of Autoimmunity-Related Genes in Melanoma
Authors: Scatozza Francesca , Facchiano Antonio
Published: February 2022

(1) Background. Immune response dysregulation plays a key role in melanoma, as suggested by the substantial prognosis improvement observed under immune-modulation therapy. Similarly, the role of autoimmunity is under large investigation in melanoma and other cancers. (2) Methods. Expression of 98 autoimmunity-related genes was investigated in 1948 individuals (1024 melanoma and 924 healthy controls). Data were derived from four independent databases, namely, GEO in the selection phase, and Ist Online, GEPIA2 and GENT2, in three sequential validation-steps. ROC analyses were performed to measure the ability to discriminate melanoma from controls. Principal Component Analysis (PCA) was used to combine expression data; survival analysis was carried out on the GEPIA2 platform. (3) Results. Expression levels of NOD2, BAX, IL-18 and ADRB2 were found to be significantly different in melanoma vs. controls and discriminate melanoma from controls in an extremely effective way, either as single molecules (AUC > 0.93 in all cases) or as a profile, according to the PCA analysis. Patients showing high-expression of NOD2 and of IL-18 also show a significant survival improvement as compared to low-expression patients. (4) Conclusions. Four genes strongly related to autoimmunity show a significant altered expression in melanoma samples, highlighting the role they may play in melanoma.
Molecular Composition of Serum Exosomes Could Discriminate Rectal Cancer Patients with Different Responses to Neoadjuvant Radiotherapy
Authors: Strybel Urszula , Marczak Lukasz , Zeman Marcin , Polanski Krzysztof , Mielańczyk Łukasz , Klymenko Olesya , Samelak-Czajka Anna , Jackowiak Paulina , Smolarz Mateusz , Chekan Mykola , Zembala-Nożyńska Ewa , Widlak Piotr , Pietrowska Monika , Wojakowska Anna
Published: February 2022

Identification of biomarkers that could be used for the prediction of the response to neoadjuvant radiotherapy (neo-RT) in locally advanced rectal cancer remains a challenge addressed by different experimental approaches. Exosomes and other classes of extracellular vesicles circulating in patients’ blood represent a novel type of liquid biopsy and a source of cancer biomarkers. Here, we used a combined proteomic and metabolomic approach based on mass spectrometry techniques for studying the molecular components of exosomes isolated from the serum of rectal cancer patients with different responses to neo-RT. This allowed revealing several proteins and metabolites associated with common pathways relevant for the response of rectal cancer patients to neo-RT, including immune system response, complement activation cascade, platelet functions, metabolism of lipids, metabolism of glucose, and cancer-related signaling pathways. Moreover, the composition of serum-derived exosomes and a whole serum was analyzed in parallel to compare the biomarker potential of both specimens. Among proteins that the most properly discriminated good and poor responders were GPLD1 (AUC = 0.85, accuracy of 74%) identified in plasma as well as C8G (AUC = 0.91, accuracy 81%), SERPINF2 (AUC = 0.91, accuracy 79%) and CFHR3 (AUC = 0.90, accuracy 81%) identified in exosomes. We found that the proteome component of serum-derived exosomes has the highest capacity to discriminate samples of patients with different responses to neo-RT when compared to the whole plasma proteome and metabolome. We concluded that the molecular components of exosomes are associated with the response of rectal cancer patients to neo-RT and could be used for the prediction of such response.
Current Status of the Spectrum and Therapeutics of Helicobacter pylori-Negative Mucosa-Associated Lymphoid Tissue Lymphoma
Authors: Kuo Sung-Hsin , Yeh Kun-Huei , Lin Chung-Wu , Liou Jyh-Ming , Wu Ming-Shiang , Chen Li-Tzong , Cheng Ann-Lii
Published: February 2022

Helicobacter pylori (HP)-unrelated mucosa-associated lymphoid tissue (MALT) lymphoma includes the majority of extragastric MALT lymphomas and a small proportion of gastric MALT lymphomas. Although the role of first-line antibiotics in treating HP-negative gastric MALT lymphomas remains controversial, HP eradication therapy (HPE)-like regimens may result in approximately 20–30% complete remission (CR) for patients with localized HP-negative gastric MALT lymphoma. In these patients, H. heilmannii, H. bizzozeronii, and H. suis were detected in sporadic gastric biopsy specimens. Extragastric MALT lymphoma is conventionally treated with radiotherapy for localized disease and systemic chemotherapy for advanced and metastatic diseases. However, a proportion of extragastric MALT lymphomas, such as ocular adnexal lesions and small intestinal lesions, were reported to be controlled by antibiotics for Chlamydophila psittaci and Campylobacter jejuni, respectively. Some extragastric MALT lymphomas may even respond to first-line HPE. These findings suggest that some antibiotic-responsive tumors may exist in the family of HP-negative MALT lymphomas. Two mechanisms underlying the antibiotic responsiveness of HP-negative MALT lymphoma have been proposed. First, an HPE-like regimen may eradicate the antigens of unknown bacteria. Second, clarithromycin (the main component of HPE) may have direct or indirect antineoplastic effects, thus contributing to the CR of these tumors. For antibiotic-unresponsive HP-negative MALT lymphoma, high-dose macrolides and immunomodulatory drugs, such as thalidomide and lenalidomide, have reported sporadic success. Further investigation of new treatment regimens is warranted.
VISTA in Soft Tissue Sarcomas: A Perspective for Immunotherapy?
Authors: Albertsmeier Markus , Altendorf-Hofmann Annelore , Lindner Lars H. , Issels Rolf D. , Kampmann Eric , Dürr Hans-Roland , Angele Martin K. , Klauschen Frederick , Werner Jens , Jungbluth Achim A. , Knösel Thomas
Published: February 2022

(1) Background: V domain immunoglobulin suppressor of T cell activation (VISTA) plays a critical role in antitumor immunity and may be a valuable target in cancer immunotherapy. To date, it has never been studied in a large and well-characterised cohort of soft tissue sarcomas (STS). (2) Methods: Using immunohistochemistry, we examined VISTA expression in tumour tissues of 213 high-risk STS. We then analysed whether VISTA was associated with other clinicopathological parameters, including tumour-infiltrating lymphocyte (TIL) counts, programmed death receptor-1 (PD1), programmed death ligand-1 (PDL1), CD3, grading, and long-term survival. (3) Results: We observed VISTA expression in 96 (45%) of 213 specimens with distinct patterns ranging from 26 to 63% for histological subtypes. VISTA was associated with higher grade (G3 vs. G2, p = 0.019), higher TIL counts (p = 0.033), expression of PD1 (p = 0.046), PDL1 (p = 0.031), and CD3+ (p = 0.023). In patients without CD3+ TILs, 10-year survival was higher when VISTA was expressed compared to when there was no VISTA expression (p = 0.013). In a multivariate analysis, VISTA expression was independently associated with prolonged survival (p = 0.043). (4) Conclusions: VISTA is expressed in different STS subtypes and is associated with increased TILs, PD-1, PD-L1, and CD3 expression. Patients with VISTA+ tumours show improved survival. These results may help define future immunotherapeutic approaches in STS.
Identification of Tissue-Specific Gene Clusters Induced by DNA Demethylation in Lung Adenocarcinoma: More Than Germline Genes
Authors: Diacofotaki Anna , Loriot Axelle , De Smet Charles
Published: February 2022

Genome-wide loss of DNA methylation is commonly observed in human cancers, but its impact on the tumor transcriptome remains ill-defined. Previous studies demonstrated that this epigenetic alteration causes aberrant activation of a germline-specific gene expression program. Here, we examined if DNA hypomethylation in tumors also leads to de-repression of gene clusters with other tissue specificities. To this end, we explored transcriptomic and methylomic datasets from human lung adenocarcinoma (LUAD) cell lines, normal lung, and lung alveolar type II cells, considered as the origin of LUAD. Interestingly, DNA demethylation in LUAD cell lines was associated with activation of not only germline-specific (CG) genes, but also gene clusters displaying specific expression in the gastrointestinal tract (GI), or in stratified epithelia (SE). Consistently, genes from all three clusters showed highly specific patterns of promoter methylation among normal tissues and cell types, and were generally sensitive to induction by a DNA demethylating agent. Analysis of TCGA datasets confirmed that demethylation and activation of CG, GI and SE genes also occurs in vivo in LUAD tumor tissues, in association with global genome hypomethylation. For genes of the GI cluster, we demonstrated that HNF4A is a necessary factor for transcriptional activation following promoter demethylation. Interestingly, expression of several SE genes, in particular FAM83A, correlated with both tumor grade and reduced patient survival. Together, our study uncovers novel cell-type specific gene clusters that become aberrantly activated in LUAD tumors in association with genome-wide hypomethylation.
Shaping of Hepatic Ischemia/Reperfusion Events: The Crucial Role of Mitochondria
Authors: Teodoro João S. , Da Silva Rui T. , Machado Ivo F. , Panisello-Roselló Arnau , Roselló-Catafau Joan , Rolo Anabela P. , Palmeira Carlos M.
Published: February 2022

Hepatic ischemia reperfusion injury (HIRI) is a major hurdle in many clinical scenarios, including liver resection and transplantation. Various studies and countless surgical events have led to the observation of a strong correlation between HIRI induced by liver transplantation and early allograft-dysfunction development. The detrimental impact of HIRI has driven the pursuit of new ways to alleviate its adverse effects. At the core of HIRI lies mitochondrial dysfunction. Various studies, from both animal models and in clinical settings, have clearly shown that mitochondrial function is severely hampered by HIRI and that its preservation or restoration is a key indicator of successful organ recovery. Several strategies have been thus implemented throughout the years, targeting mitochondrial function. This work briefly discusses some the most utilized approaches, ranging from surgical practices to pharmacological interventions and highlights how novel strategies can be investigated and implemented by intricately discussing the way mitochondrial function is affected by HIRI.
Reinfection of Transplanted Livers in HCV- and HCV/HIV-Infected Patients Is Characterized by a Different MicroRNA Expression Profile
Authors: Dalla Emiliano , Bulfoni Michela , Cesselli Daniela , Pravisani Riccardo , Hidaka Masaaki , Eguchi Susumu , Baccarani Umberto
Published: February 2022

Background: After liver transplantation, HCV/HIV co-infected patients present, compared to the HCV mono-infected ones, increased HCV viral load, rapid progression to liver fibrosis and higher mortality. Liver biopsies (LB), obtained routinely 6 months after transplantation, represent a unique model to assess the early events related to graft re-infection. Here, we used miRNA sequencing of LB obtained from both HCV-and HCV/HIV-infected recipients, to identify transcriptional profiles able to explain the more severe outcome of these latter. Methods: miRNAs of 3 healthy livers, 3 HCV-LB and 3 HCV/HIV-LB were sequenced by Illumina HiSeq2500 platform. The DIANA-miRPath v3.0 webserver and DIANA-microT-CDS algorithm (v5.0) were used to characterize the functions of differentially expressed (DE-) miRNAs, querying the KEGG and Gene Ontology-Biological Process databases. Results: LB obtained from infected patients were characterized, with respect to controls, by a miRNA profile related to viral infection, immune system signaling and DNA damage in HCV-induced carcinogenesis. Instead, HCV-LB and HCV/HIV-LB differed in the expression of miRNAs involved in immunological and apoptotic processes and in extracellular matrix remodeling. Conclusions: liver reinfection processes are associated with early miRNA changes. Further studies are necessary to establish their prognostic role and possible actionability.
A Review on Transcriptional Responses of Interactions between Insect Vectors and Plant Viruses
Authors: Catto Michael A. , Mugerwa Habibu , Myers Brendon K. , Pandey Sudeep , Dutta Bhabesh , Srinivasan Rajagopalbabu
Published: February 2022

This review provides a synopsis of transcriptional responses pertaining to interactions between plant viruses and the insect vectors that transmit them in diverse modes. In the process, it attempts to catalog differential gene expression pertinent to virus–vector interactions in vectors such as virus reception, virus cell entry, virus tissue tropism, virus multiplication, and vector immune responses. Whiteflies, leafhoppers, planthoppers, and thrips are the main insect groups reviewed, along with aphids and leaf beetles. Much of the focus on gene expression pertinent to vector–virus interactions has centered around whole-body RNA extraction, whereas data on virus-induced tissue-specific gene expression in vectors is limited. This review compares transcriptional responses in different insect groups following the acquisition of non-persistent, semi-persistent, and persistent (non-propagative and propagative) plant viruses and identifies parallels and divergences in gene expression patterns. Understanding virus-induced changes in vectors at a transcriptional level can aid in the identification of candidate genes for targeting with RNAi and/or CRISPR editing in insect vectors for management approaches.
Altered Phenotype and Enhanced Antibody-Producing Ability of Peripheral B Cells in Mice with Cd19-Driven Cre Expression
Authors: Zhao Ying , Zhao Sai , Qin Xiao-Yuan , He Ting-Ting , Hu Miao-Miao , Gong Zheng , Wang Hong-Min , Gong Fang-Yuan , Gao Xiao-Ming , Wang Jun
Published: February 2022

Given the importance of B lymphocytes in inflammation and immune defense against pathogens, mice transgenic for Cre under the control of Cd19 promoter (Cd19Cre/+ mice) have been widely used to specifically investigate the role of loxP-flanked genes in B cell development/function. However, impacts of expression/insertion of the Cre transgene on the phenotype and function of B cells have not been carefully studied. Here, we show that the number of marginal zone B and B1a cells was selectively reduced in Cd19Cre/+ mice, while B cell development in the bone marrow and total numbers of peripheral B cells were comparable between Cd19Cre/+ and wild type C57BL/6 mice. Notably, humoral responses to both T cell-dependent and independent antigens were significantly increased in Cd19Cre/+ mice. We speculate that these differences are mainly attributable to reduced surface CD19 levels caused by integration of the Cre-expressing cassette that inactivates one Cd19 allele. Moreover, our literature survey showed that expression of Cd19Cre/+ alone may affect the development/progression of inflammatory and anti-infectious responses. Thus, our results have important implications for the design and interpretation of results on gene functions specifically targeted in B cells in the Cd19Cre/+ mouse strain, for instance, in the context of (auto) inflammatory/infectious diseases.
Mitofusin-2 Negatively Regulates Melanogenesis by Modulating Mitochondrial ROS Generation
Authors: Tanwar Jyoti , Saurav Suman , Basu Reelina , Singh Jaya Bharti , Priya Anshu , Dutta Maitreyee , Santhanam Uma , Joshi Manoj , Madison Stephen , Singh Archana , Nair Nirmala , Gokhale Rajesh S. , Motiani Rajender K.
Published: February 2022

Inter-organellar communication is emerging as one of the most crucial regulators of cellular physiology. One of the key regulators of inter-organellar communication is Mitofusin-2 (MFN2). MFN2 is also involved in mediating mitochondrial fusion–fission dynamics. Further, it facilitates mitochondrial crosstalk with the endoplasmic reticulum, lysosomes and melanosomes, which are lysosome-related organelles specialized in melanin synthesis within melanocytes. However, the role of MFN2 in regulating melanocyte-specific cellular function, i.e., melanogenesis, remains poorly understood. Here, using a B16 mouse melanoma cell line and primary human melanocytes, we report that MFN2 negatively regulates melanogenesis. Both the transient and stable knockdown of MFN2 leads to enhanced melanogenesis, which is associated with an increase in the number of mature (stage III and IV) melanosomes and the augmented expression of key melanogenic enzymes. Further, the ectopic expression of MFN2 in MFN2-silenced cells leads to the complete rescue of the phenotype at the cellular and molecular levels. Mechanistically, MFN2-silencing elevates mitochondrial reactive-oxygen-species (ROS) levels which in turn increases melanogenesis. ROS quenching with the antioxidant N-acetyl cysteine (NAC) reverses the MFN2-knockdown-mediated increase in melanogenesis. Moreover, MFN2 expression is significantly lower in the darkly pigmented primary human melanocytes in comparison to lightly pigmented melanocytes, highlighting a potential contribution of lower MFN2 levels to higher physiological pigmentation. Taken together, our work establishes MFN2 as a novel negative regulator of melanogenesis.