bluuebunny/crossref_metadata_2025 huggingface dataset:
Host Serum Proteins as Potential Biomarkers of Bovine Tuberculosis Resistance Phenotype
Authors: Mazorra-Carrillo Jorge Luis , Alcaraz-López Omar Antonio , López-Rincón Gonzalo , Villarreal-Ramos Bernardo , Gutiérrez-Pabello José A. , Esquivel-Solís Hugo
Published: November 2021

Eradication of bovine tuberculosis (bTB) continues to be a worldwide challenge. The lack of reliable vaccines dampens the control and eradication programs of Mycobacterium bovis infection and spread. Selection and breeding of cattle resistant to M. bovis infection would greatly enhance the effectiveness of bTB eradication programs. Here, we have evaluated the potential of serum proteins as biomarkers of cattle resistance to bTB in Holstein-Friesian cows, 6–8-year-old, born and raised in similar conditions in herds with bTB prevalence >30%. Serum proteins obtained from uninfected cows (bTB-resistant; R) were compared to those from infected cows (bTB-susceptible; S), defined by a negative or positive bTB diagnosis, respectively. bTB diagnosis included: (i) single intradermal (caudal fold) tuberculin test, (ii) whole blood IFN-gamma test, (iii) gross visible lesions in lymph nodes and lungs by inspection at the abattoir, and (iv) a bacteriological culture for M. bovis. Using 2D-GE and LC-ESI-MS/MS, we found higher expression levels of primary amine oxidase (AO), complement component 5 (C5), and serotransferrin (TF) in R cattle than S cattle. In-house developed and standardized ELISAs for these novel biomarkers showed the best sensitivities of 72, 77, 77%, and specificities of 94, 94, 83%, for AO, C5, and TF, respectively. AUC-ROC (95% CI) values of 0.8935 (0.7906–0.9964), 0.9290 (0.8484–1.010), and 0.8580 (0.7291–0.9869) were obtained at cut-off points of 192.0, 176.5 ng/ml, and 2.1 mg/ml for AO, C5, and TF, respectively. These proteins are involved in inflammatory/immunomodulatory responses to infections and may provide a novel avenue of research to determine the mechanisms of protection against bTB. Overall, our results indicate that these proteins could be novel biomarkers to help identify cattle resistant to bTB, which in turn could be used to strengthen the effectiveness of existing eradication programs against bTB.
A Short-Term Altrenogest Treatment Post-weaning Followed by Superovulation Reduces Pregnancy Rates and Embryo Production Efficiency in Multiparous Sows
Authors: Gonzalez-Ramiro Henar , Cuello Cristina , Cambra Josep M. , Gonzalez-Plaza Alejandro , Vazquez Juan M. , Vazquez Jose L. , Rodriguez-Martinez Heriberto , Gil Maria A. , Lucas-Sanchez Alejandro , Parrilla Inmaculada , Martinez Emilio A.
Published: November 2021

Although embryo transfer (ET) is a biotechnology ready for the swine industry, there are factors to be solved, the availability of embryo donors as one. Multiparous sows as donors ought to be considered since weaning is a natural and efficient method for estrus synchronization. In addition, superovulation treatments at weaning are effective in increasing the efficiency of donor embryo production. However, ET programs typically require more donors than those available from a single weaning, imposing grouping several weanings to establish a batch for ET. Since short-term administration of Altrenogest is effective in delaying estrus after weaning without effects on ovulation and embryo development, we investigated how Altrenogest combined with superovulation would affect reproductive parameters and embryo quality and quantity of weaned multiparous donor sows. The sows were administered Altrenogest from the day of weaning for 14 (SS-14 group; N = 26), 7 (SS-7 group; N = 31) and 4 (SS-4 group; N = 32) days. The sows were superovulated with eCG 24 h after the last administration of Altrenogest and with hCG at the onset of estrus. Sows not treated with Altrenogest that were superovulated with eCG 24 h post-weaning and hCG at the onset of estrus (SC group; N = 37) and sows with natural estrus after weaning (C group; N = 34) were used as control groups. The percentage of sows showing estrus within 10 days was not affected by the treatment, but the interval from Altrenogest withdrawal to estrus was longer (P < 0.05) in the SS groups than the interval from weaning to estrus in the controls. SS treatments increased (P < 0.05) the percentage of sows with ovarian cysts and the development of polycystic ovaries. The pregnancy and the fertilization rates, and the overall embryo production efficiency were also negatively affected by the SS treatments (P < 0.05). Interestingly, almost 70% of the structures classified as unfertilized oocytes or degenerated embryos in sows from the SS groups were immature oocytes. In conclusion, although superovulation of weaned sows was highly efficient, short-term administration of Altrenogest in combination with superovulation had negative effects on most of the reproductive parameters assessed, particularly affecting the overall efficiency of pregnancy and embryo production.
Characterizing Pet Acquisition and Retention During the COVID-19 Pandemic
Authors: Hoffman Christy L. , Thibault Melissa , Hong Julie
Published: November 2021

In March 2020, Americans began experiencing numerous lifestyle changes due to the COVID-19 pandemic. Some reports have suggested that pet acquisition and ownership increased during this period, and some have suggested shelters and rescues will be overwhelmed once pandemic-related restrictions are lifted and lifestyles shift yet again. In May 2021, the ASPCA hired the global market research company Ipsos to conduct a general population survey that would provide a more comprehensive picture of pet ownership and acquisition during the pandemic. Although pet owners care for a number of species, the term pet owner in this study specifically refers to those who had dogs and/or cats. One goal of the survey was to determine whether data from a sample of adults residing in the United States would corroborate findings from national shelter databases indicating that animals were not being surrendered to shelters in large numbers. Furthermore, this survey gauged individuals' concerns related to the lifting of COVID-19 restrictions, and analyses examined factors associated with pet owners indicating they were considering rehoming an animal within the next 3 months. The data showed that pet ownership did not increase during the pandemic and that pets may have been rehomed in greater numbers than occurs during more stable times. Importantly, rehomed animals were placed with friends, family members, and neighbors more frequently than they were relinquished to animal shelters and rescues. Findings associated with those who rehomed an animal during the pandemic, or were considering rehoming, suggest that animal welfare organizations have opportunities to increase pet retention by providing resources regarding pet-friendly housing and affordable veterinary options and by helping pet owners strategize how to incorporate their animals into their post-pandemic lifestyles.
Effects of Dietary Supplementation with Epigallocatechin Gallate on Meat Quality and Muscle Antioxidant Capacity of Broilers Subjected to Acute Heat Stress
Authors: Zhao Fei , Wang Xiaocheng , Li Yang , Chen Xingyong , Geng Zhaoyu , Zhang Cheng
Published: November 2021

This study evaluated epigallocatechin gallate’s (EGCG’s, 400 mg/kg) effect on meat quality and muscle antioxidant status of broilers under acute heat stress (AHS). A total of 144 21-day-old male Huainan partridge chickens were randomly allocated to the EGCG-free group (12 replicates) and the EGCG group (6 replicates). On day 94, the EGCG-free group was divided into the control group (CON) and the AHS group, and then AHS group and EGCG group (identified as AHS + EGCG group) were treated with AHS (33 ± 1 °C for 12 h). AHS increased (p < 0.05) L*24h, drip loss, muscle lactic acid, malondialdehyde (MDA) contents, and kelch-like ECH-associated protein 1 (Keap1) mRNA level, and decreased (p < 0.05) eviscerated percentage, pH24h, a*, muscle total superoxide dismutase (T-SOD) activity, the ratio of T-SOD/MDA and glutathione peroxidase /MDA, glycogen content, and nuclear factor erythroid 2-related 2 (Nrf2), catalase (CAT), NAD(P)H/quinone dehydrogenase 1 (NQO1) mRNA levels. The AHS + EGCG group exhibited lower (p < 0.05) L*24h, drip loss, muscle lactic acid, MDA contents and Keap1 mRNA level, and greater (p < 0.05) eviscerated percentage, pH24h, a*, muscle T-SOD activity, the ratio of T-SOD/MDA, Nrf2, and NQO1 mRNA levels compared with the AHS group. In conclusion, EGCG protects against AHS-impaired meat quality by improving muscle antioxidant capacity, which seems to be associated with the activation of the Nrf2 signaling pathway.
Pathognomonic Combination of Clinical Signs for Diagnosis of Vertical Root Fracture: Systematic Review of the Literature
Authors: Goldberger Tomer , Rosen Eyal , Blau-Venezia Nuphar , Tamse Aviad , Littner Dan
Published: November 2021

Introduction: Vertical root fracture (VRF) is a root-canal treatment complication and is a major reason for extraction of the root-canal-treated teeth. The diagnosis of VRF can be complicated because of absence of specific signs, symptoms, and radiographic features. A combination that includes the presence of deep pocket and a sinus tract in root-canal-treated tooth was proposed as a pathognomonic for VRF. The purpose of this study was to systematically search and evaluate the literature regarding the correlation between the clinical signs considered pathognomonic for the diagnosis of VRF, with the actual reference standard by means of systematic review of the literature. Methods: A systematic search of the literature was performed to identify studies evaluating the clinical signs considered pathognomonic for the diagnosis of VRF. The following databases were searched: Medline (PubMed), Scopus, and Cochrane Central. The identified studies were subjected to strict inclusion and exclusion criteria. Results: Initially, 1141 possible relevant articles were identified. After title and abstract screening, 40 articles were subjected to a full-text evaluation, 3 articles met the inclusion criteria and contained data regarding the prevalence of the pathognomonic combination in VRF’s-confirmed teeth. The presence of deep pocket and a sinus tract in endodontically treated teeth was found in 28% of the cases. Conclusion: To date, the current scientific knowledge regarding the correlation between the clinical symptoms considered pathognomonic for VRF diagnosis in the root-canal-treated tooth and the actual reference standard is quite low.
A Novel Composite Coding Method for Incoherent Scatter Radar
Authors: Chen Haoyi , Yuan Kai , Yao Ming , Xiong Jiawei
Published: November 2021

Many modern ionospheric studies rely on incoherent scatter radars (ISR) since this kind of radar is able to detect various ionospheric parameters over very long ranges. The performance of ISR significantly depends on its coding system. In recent decades, a new type of coding system, which is the so-called composite coding, was presented. It used to be constructed by using a certain code to modulate alternating code to achieve better detection resolution and anti-noise performance for ISRs. In the present study, a new composite coding system was presented, which is constructed based on complementary codes and alternating codes. In this paper, the performance of the new composite code will be compared with that of several traditional codes to show that the new composite code can help to improve the detection performance of the ISR. According to the analysis based on the ambiguity function, the present composite coding system helps to improve the range resolution and detection range for ISR detections. In addition, numerical tests on anti-noise performance show that the complementary composite coding system has a good anti-noise performance and helps to reduce the necessary times of incoherent integration. As a result, the composite coding system can improve the time resolution.
Regional Air Pollutant Characteristics and Health Risk Assessment of Large Cities in Northeast China
Authors: Fang Chunsheng , Gao Hanbo , Li Zhuoqiong , Wang Ju
Published: November 2021

This study systematically investigated the pollution characteristics of atmospheric O3 and PM2.5, regional transport, and their health risks in three provincial capitals in northeast China during 2016–2020. The results show that O3 concentrations showed a trend of high summer and low winter, while PM2.5 concentrations showed a trend of high winter and low summer during these five years. The results of the correlation analysis indicate that external sources contribute more O3, while PM2.5 is more from local sources. The backward trajectory clustering analysis results showed that Changchun had the highest share of northwest trajectory with a five-year average value of 67.89%, and the city with the highest percentage of southwest trajectory was Shenyang with a five-year average value of 23.95%. The backward trajectory clustering analysis results showed that the share of the northwest trajectory decreased and the share of the southwest trajectory increased for all three cities in 2020 compared to 2016. The results of the potential source contribution function (PSCF) and concentration weighting trajectory (CWT) analysis showed that the main potential source areas and high concentration contribution areas for PM2.5 in the northeast were concentrated in Mongolia, Inner Mongolia, Shandong Province, and the northeast, and for O3 were mainly located in Shandong, Anhui, and Jiangsu Provinces, and the Yellow Sea and Bohai Sea. The non-carcinogenic risk of PM2.5 in Harbin was high with a HQ of 2.04, while the other cities were at acceptable levels (HQ < 0.69) and the non-carcinogenic risk of O3 was acceptable in all three cities (HQ < 0.22). However, PM2.5 had a high carcinogenic risk (4 × 10−4 < CR < 0.44) and further treatment is needed to reduce the risk.
Correlation of Periodontal Bacteria with Chronic Inflammation Present in Patients with Metabolic Syndrome
Authors: Ghitea Timea Claudia
Published: November 2021

Metabolic syndrome (MS) is correlated with many chronic diseases, and so far is moderately followed and treated. The present study follows a correlation of the presence of pathogens (Fusobacterium nucleatum, Bacteroides forsythus, and others) in the gingival crevicular fluid and MS. (1) An important role in the fight against MS is to reduce fat mass, inflammatory mediators, and prevent cytokine-associated diseases. (2) A group of 111 people with MS was studied, divided into 3 groups. The control group (CG) received no treatment for either periodontitis or MS. The diet therapy group (DG) followed a clinical diet therapy specific to MS, and the diet therapy and sports group (DSG) in addition to diet therapy introduced regular physical activity; (3) A statistically significant worsening of periodontopathogens was observed correlated with the advancement of MS (increase in fat mass, visceral fat, and ECW/TBW ratio) in the CG group. In the case of DG and DSG groups, an improvement of the parameters was observed, including periodontal diseases. Therefore, anti-inflammatory diet therapy contributes to the reduction of gingival inflammation and thus contributes to the reduction of the development of pathogenic bacteria in the gingival, responsible for the development of periodontal disease and directly by other chronic diseases.
Artefacts in Volume Data Generated with High Resolution Episcopic Microscopy (HREM)
Authors: Reissig Lukas F. , Geyer Stefan H. , Rose Julia , Prin Fabrice , Wilson Robert , Szumska Dorota , Galli Antonella , Tudor Catherine , White Jacqueline K. , Mohun Tim J. , Weninger Wolfgang J.
Published: November 2021

High resolution episcopic microscopy (HREM) produces digital volume data by physically sectioning histologically processed specimens, while capturing images of the subsequently exposed block faces. Our study aims to systematically define the spectrum of typical artefacts inherent to HREM data and to research their effect on the interpretation of the phenotype of wildtype and mutant mouse embryos. A total of 607 (198 wildtypes, 409 mutants) HREM data sets of mouse embryos harvested at embryonic day (E) 14.5 were systematically and comprehensively examined. The specimens had been processed according to essentially identical protocols. Each data set comprised 2000 to 4000 single digital images. Voxel dimensions were 3 × 3 × 3 µm3. Using 3D volume models and virtual resections, we identified a number of characteristic artefacts and grouped them according to their most likely causality. Furthermore, we highlight those that affect the interpretation of embryo data and provide examples for artefacts mimicking tissue defects and structural pathologies. Our results aid in optimizing specimen preparation and data generation, are vital for the correct interpretation of HREM data and allow distinguishing tissue defects and pathologies from harmless artificial alterations. In particular, they enable correct diagnosis of pathologies in mouse embryos serving as models for deciphering the mechanisms of developmental disorders.
Dose-Dependent Effects of a Novel Selective EP4 Prostaglandin Receptor Agonist on Treatment of Critical Size Femoral Bone Defects in a Rat Model
Authors: Vater Corina , Mehnert Elisabeth , Bretschneider Henriette , Bolte Julia , Findeisen Lisa , Matuszewski Lucas-Maximilian , Zwingenberger Stefan
Published: November 2021

Difficulties in treating pseudarthrosis and critical bone defects are still evident in physicians’ clinical routines. Bone morphogenetic protein 2 (BMP-2) has shown promising osteoinductive results but also considerable side effects, not unexpected given that it is a morphogen. Thus, the bone regenerative potential of the novel selective, non-morphogenic EP4 prostaglandin receptor agonist KMN-159 was investigated in this study. Therefore, mineralized collagen type-1 matrices were loaded with different amounts of BMP-2 or KMN-159 and implanted into a 5 mm critical-sized femoral defect in rats. After 12 weeks of observation, micro-computed tomography scans were performed to analyze the newly formed bone volume (BV) and bone mineral density (BMD). Histological analysis was performed to evaluate the degree of defect healing and the number of vessels, osteoclasts, and osteoblasts. Data were evaluated using Kruskal-Wallis followed by Dunn’s post hoc test. As expected, animals treated with BMP-2, the positive control for this model, showed a high amount of newly formed BV as well as bone healing. For KMN-159, a dose-dependent effect on bone regeneration could be observed up to a dose optimum, demonstrating that this non-morphogenic mechanism of action can stimulate bone formation in this model system.
Progress of Microfluidic Continuous Separation Techniques for Micro-/Nanoscale Bioparticles
Authors: Choe Se-woon , Kim Bumjoo , Kim Minseok
Published: November 2021

Separation of micro- and nano-sized biological particles, such as cells, proteins, and nucleotides, is at the heart of most biochemical sensing/analysis, including in vitro biosensing, diagnostics, drug development, proteomics, and genomics. However, most of the conventional particle separation techniques are based on membrane filtration techniques, whose efficiency is limited by membrane characteristics, such as pore size, porosity, surface charge density, or biocompatibility, which results in a reduction in the separation efficiency of bioparticles of various sizes and types. In addition, since other conventional separation methods, such as centrifugation, chromatography, and precipitation, are difficult to perform in a continuous manner, requiring multiple preparation steps with a relatively large minimum sample volume is necessary for stable bioprocessing. Recently, microfluidic engineering enables more efficient separation in a continuous flow with rapid processing of small volumes of rare biological samples, such as DNA, proteins, viruses, exosomes, and even cells. In this paper, we present a comprehensive review of the recent advances in microfluidic separation of micro-/nano-sized bioparticles by summarizing the physical principles behind the separation system and practical examples of biomedical applications.
Neural Decoding of EEG Signals with Machine Learning: A Systematic Review
Authors: Saeidi Maham , Karwowski Waldemar , Farahani Farzad V. , Fiok Krzysztof , Taiar Redha , Hancock P. A. , Al-Juaid Awad
Published: November 2021

Electroencephalography (EEG) is a non-invasive technique used to record the brain’s evoked and induced electrical activity from the scalp. Artificial intelligence, particularly machine learning (ML) and deep learning (DL) algorithms, are increasingly being applied to EEG data for pattern analysis, group membership classification, and brain-computer interface purposes. This study aimed to systematically review recent advances in ML and DL supervised models for decoding and classifying EEG signals. Moreover, this article provides a comprehensive review of the state-of-the-art techniques used for EEG signal preprocessing and feature extraction. To this end, several academic databases were searched to explore relevant studies from the year 2000 to the present. Our results showed that the application of ML and DL in both mental workload and motor imagery tasks has received substantial attention in recent years. A total of 75% of DL studies applied convolutional neural networks with various learning algorithms, and 36% of ML studies achieved competitive accuracy by using a support vector machine algorithm. Wavelet transform was found to be the most common feature extraction method used for all types of tasks. We further examined the specific feature extraction methods and end classifier recommendations discovered in this systematic review.
The Role of Expectation and Beliefs on the Effects of Non-Invasive Brain Stimulation
Authors: Braga Miriam , Barbiani Diletta , Emadi Andani Mehran , Villa-Sánchez Bernardo , Tinazzi Michele , Fiorio Mirta
Published: November 2021

Non-invasive brain stimulation (NIBS) techniques are used in clinical and cognitive neuroscience to induce a mild magnetic or electric field in the brain to modulate behavior and cortical activation. Despite the great body of literature demonstrating promising results, unexpected or even paradoxical outcomes are sometimes observed. This might be due either to technical and methodological issues (e.g., stimulation parameters, stimulated brain area), or to participants’ expectations and beliefs before and during the stimulation sessions. In this narrative review, we present some studies showing that placebo and nocebo effects, associated with positive and negative expectations, respectively, could be present in NIBS trials, both in experimental and in clinical settings. The lack of systematic evaluation of subjective expectations and beliefs before and after stimulation could represent a caveat that overshadows the potential contribution of placebo and nocebo effects in the outcome of NIBS trials.
Testing the Foreign Language Effect on Cognitive Reflection in Older Adults
Authors: Vega-Mendoza Mariana , Hansson Patrik , Sörman Daniel Eriksson , Ljungberg Jessica K.
Published: November 2021

An increasing number of people around the world communicate in more than one language, resulting in them having to make decisions in a foreign language on a daily basis. Interestingly, a burgeoning body of literature suggests that people’s decision-making is affected by whether they are reasoning in their native language (NL) or their foreign language (FL). According to the foreign language effect (FLe), people are less susceptible to bias in many decision-making tasks and more likely to display utilitarian cost-benefit analysis in moral decision-making when reasoning in a FL. While these differences have often been attributed to a reduced emotionality in the FL, an emerging body of literature has started to test the extent to which these could be attributable to increased deliberation in the FL. The present study tests whether increased deliberation leads to a FLe on cognitive reflection in a population of older adults (Mage = 65.1), from the successful aging project in Umeå, Sweden. We explored whether performance on a 6-item version of the cognitive reflection test (CRT) adapted to Swedish would differ between participants for whom Swedish was their NL and those for whom Swedish was their FL. The CRT is a task designed to elicit an incorrect, intuitive answer. In order to override the intuitive answer, one requires engaging in deliberative, analytical thinking to determine the correct answer. Therefore, we hypothesized that if thinking in a FL increases deliberation, then those performing the task in their FL would exhibit higher accuracy rates than those performing in their NL. Our results showed that age and level of education predicted performance on the task but performance on the CRT did not differ between the NL and the FL groups. In addition, in the FL group, proficiency in the FL was not related to performance in the CRT. Our results, therefore, do not provide evidence that thinking in a FL increases deliberation in a group of older adults performing a logical reasoning task that is not typically associated with an emotional connotation.
Theoretical Evaluation of the Impact of Hyperthermia in Combination with Radiation Therapy in an Artificial Immune—Tumor-Ecosystem
Authors: Scheidegger Stephan , Mingo Barba Sergio , Gaipl Udo S.
Published: November 2021

There is some evidence that radiotherapy (RT) can trigger anti-tumor immune responses. In addition, hyperthermia (HT) is known to be a tumor cell radio-sensitizer. How HT could enhance the anti-tumor immune response produced by RT is still an open question. The aim of this study is the evaluation of potential dynamic effects regarding the adaptive immune response induced by different combinations of RT fractions with HT. The adaptive immune system is considered as a trainable unit (perceptron) which compares danger signals released by necrotic or apoptotic cell death with the presence of tumor- and host tissue cell population-specific molecular patterns (antigens). To mimic the changes produced by HT such as cell radio-sensitization or increase of the blood perfusion after hyperthermia, simplistic biophysical models were included. To study the effectiveness of the different RT+HT treatments, the Tumor Control Probability (TCP) was calculated. In the considered scenarios, the major effect of HT is related to the enhancement of the cell radio-sensitivity while perfusion or heat-based effects on the immune system seem to contribute less. Moreover, no tumor vaccination effect has been observed. In the presented scenarios, HT boosts the RT cell killing but it does not fundamentally change the anti-tumor immune response.
Prognostic Significance of CSF-1R Expression in Early Invasive Breast Cancer
Authors: Riaz Nazia , Burugu Samantha , Cheng Angela S. , Leung Samuel C. Y. , Gao Dongxia , Nielsen Torsten O.
Published: November 2021

Colony-stimulating factor-1 receptor (CSF-1R) signaling promotes an immune suppressive microenvironment enriched in M2 macrophages. Given that CSF-1R inhibitors are under investigation in clinical trials, including in breast cancer, CSF-1R expression and association with immune biomarkers could identify patients who derive greater benefit from combination with immunotherapies. TIMER2.0 and bc-GenExMiner v4.7 were used to assess the correlation of CSF1R mRNA with immune infiltrates and prognosis. Following a prespecified training–validation approach, an optimized immunohistochemistry assay was applied to assess CSF-1R on carcinoma cells and macrophages on breast cancer tissue microarray series representing 2384 patients, coupled to comprehensive clinicopathological, biomarker, and outcome data. Significant positive correlations were observed between CSF1R mRNA and immune infiltrates. High carcinoma CSF-1R correlated with grade 3 tumors >2 cm, hormone receptor negativity, high Ki67, immune checkpoint biomarkers, and macrophages expressing CSF-1R and CD163. High carcinoma CSF-1R was significantly associated with poor survival in univariate and multivariate analyses. Adverse prognostic associations were retained in ER+ cases regardless of the presence of CD8+ T cells. CSF-1R+ macrophages were not prognostic. High carcinoma CSF-1R is associated with aggressive breast cancer biology and poor prognosis, particularly in ER+ cases, and identifies patients in whom biomarker-directed CSF-1R therapies may yield superior therapeutic responses.
Her2-Positive Cancers and Antibody-Based Treatment: State of the Art and Future Developments
Authors: Morales Serafin , Gasol Ariadna , Sanchez Douglas Rene
Published: November 2021

HER2 positive breast cancer represent about 20% of all breast cancer subtypes and it was considered the subtype with the worst prognosis until the discovery of therapies directed against the HER2 protein. The determination of the status of the HER2 must be very precise and well managed to identify this subtype, and there are very specific and updated guides that allow its characterization to be adjusted. Treatment in local disease has been considerably improved with less aggressive and highly effective approaches and very high cure rates. In metastatic disease, average median survival rates of 5 years have been achieved. New highly active molecules have also been discovered that allow disease control in very complicated situations. This article reviews all these options that can be used for the management of this disease.
Results of Radiation Therapy as Local Ablative Therapy for Oligometastatic Non-Small Cell Lung Cancer
Authors: Billing David L. , Rimner Andreas
Published: November 2021

Oligometastatic cancer is characterized by a limited number of metastatic deposits. Compared with lung cancer patients who have more widespread disease, oligometastatic lung cancer patients have more favorable survival outcomes. Therefore, it has been hypothesized that local ablative therapy (LAT) directed at the metastatic deposits in addition to standard-of-care systemic therapy may further improve survival outcomes in oligometastatic lung cancer patients. One LAT modality that has been utilized in oligometastatic lung cancer is radiation therapy. In particular, ultra-hypofractionated radiotherapy, also known as stereotactic body radiotherapy (SBRT), has been shown to provide excellent local control with a favorable safety profile. Here, we reviewed the retrospective studies and prospective trials that have deployed radiation therapy as LAT in oligometastatic lung cancer, including randomized studies showing benefits for progression-free survival and overall survival with the addition of LAT. We also discuss the impact of targeted therapies and immunotherapy on radiation as LAT.
Update on Preclinical Development and Clinical Translation of Cholecystokinin-2 Receptor Targeting Radiopharmaceuticals
Authors: von Guggenberg Elisabeth , Kolenc Petra , Rottenburger Christof , Mikołajczak Renata , Hubalewska-Dydejczyk Alicja
Published: November 2021

The cholecystokinin-2 receptor (CCK2R) has been a target of interest for molecular imaging and targeted radionuclide therapy for two decades. However, so far CCK2R targeted imaging and therapy has not been introduced in clinical practice. Within this review the recent radiopharmaceutical development of CCK2R targeting compounds and the ongoing clinical trials are presented. Currently, new gastrin derivatives as well as nonpeptidic substances are being developed to improve the properties for clinical use. A team of specialists from the field of radiopharmacy and nuclear medicine reviewed the available literature and summarized their own experiences in the development and clinical testing of CCK2R targeting radiopharmaceuticals. The recent clinical trials with novel radiolabeled minigastrin analogs demonstrate the potential for both applications, imaging as well as targeted radiotherapy, and reinforce the clinical applicability within a theranostic concept. The intense efforts in optimizing CCK2R targeting radiopharmaceuticals has led to new substances for clinical use, as shown in first imaging studies in patients with advanced medullary thyroid cancer. The first clinical results suggest that the wider clinical implication of CCK2R-targeted radiopharmaceuticals is reasonable.
On Efficacy of Microwave Ablation in the Thermal Treatment of an Early-Stage Hepatocellular Carcinoma
Authors: Radjenović Branislav , Sabo Martin , Šoltes Lukaš , Prnova Marta , Čičak Pavel , Radmilović-Radjenović Marija
Published: November 2021

Microwave ablation at 2.45 GHz is gaining popularity as an alternative therapy to hepatic resection with a higher overall survival rate than external beam radiation therapy and proton beam therapy. It also offers better long-term recurrence-free overall survival when compared with radiofrequency ablation. To improve the design and optimization of microwave ablation procedures, numerical models can provide crucial information. A three-dimensional model of the antenna and targeted tissue without homogeneity assumptions are the most realistic representation of the physical problem. Due to complexity and computational resources consumption, most of the existing numerical studies are based on using two-dimensional axisymmetric models to emulate actual three-dimensional cancers and surrounding tissue, which is often far from reality. The main goal of this study is to develop a fully three-dimensional model of a multislot microwave antenna immersed into liver tissue affected by early-stage hepatocellular carcinoma. The geometry of the tumor is taken from the 3D-IRCADb-01 liver tumors database. Simulations were performed involving the temperature dependence of the blood perfusion, dielectric and thermal properties of both healthy and tumoral liver tissues. The water content changes during the ablation process are also included. The optimal values of the input power and the ablation time are determined to ensure complete treatment of the tumor with minimal damage to the healthy tissue. It was found that a multislot antenna is designed to create predictable, large, spherical zones of the ablation that are not influenced by varying tissue environments. The obtained results may be useful for determining optimal conditions necessary for microwave ablation to be as effective as possible for treating early-stage hepatocellular carcinoma, with minimized invasiveness and collateral damages.
A Blueprint for Cancer-Related Inflammation and Host Innate Immunity
Authors: García-López Lucia , Adrados Isabel , Ferres-Marco Dolors , Dominguez Maria
Published: November 2021

Both in situ and allograft models of cancer in juvenile and adult Drosophila melanogaster fruit flies offer a powerful means for unravelling cancer gene networks and cancer–host interactions. They can also be used as tools for cost-effective drug discovery and repurposing. Moreover, in situ modeling of emerging tumors makes it possible to address cancer initiating events—a black box in cancer research, tackle the innate antitumor immune responses to incipient preneoplastic cells and recurrent growing tumors, and decipher the initiation and evolution of inflammation. These studies in Drosophila melanogaster can serve as a blueprint for studies in more complex organisms and help in the design of mechanism-based therapies for the individualized treatment of cancer diseases in humans. This review focuses on new discoveries in Drosophila related to the diverse innate immune responses to cancer-related inflammation and the systemic effects that are so detrimental to the host.
Aberrant Patterns of Sensory-Evoked Activity in the Olfactory Bulb of LRRK2 Knockout Mice
Authors: Maset Andrea , Albanesi Marco , di Soccio Antonio , Canova Martina , dal Maschio Marco , Lodovichi Claudia
Published: November 2021

The LRRK2 gene is the major genetic determinant of familiar Parkinson’s disease (PD). Leucine-rich repeat kinase 2 (LRRK2) is a multidomain protein involved in several intracellular signaling pathways. A wealth of evidence indicates that LRRK2 is enriched at the presynaptic compartment where it regulates vesicle trafficking and neurotransmitter release. However, whether the role of LRRK2 affects neuronal networks dynamic at systems level remains unknown. Addressing this question is critical to unravel the impact of LRRK2 on brain function. Here, combining behavioral tests, electrophysiological recordings, and functional imaging, we investigated neuronal network dynamics, in vivo, in the olfactory bulb of mice carrying a null mutation in LRRK2 gene (LRRK2 knockout, LRRK2 KO, mice). We found that LRRK2 KO mice exhibit olfactory behavioral deficits. At the circuit level, the lack of LRRK2 expression results in altered gamma rhythms and odorant-evoked activity with significant impairments, while the spontaneous activity exhibited limited alterations. Overall, our data in the olfactory bulb suggest that the multifaced role of LRRK2 has a strong impact at system level when the network is engaged in active sensory processing.
Resveratrol Contrasts LPA-Induced Ovarian Cancer Cell Migration and Platinum Resistance by Rescuing Hedgehog-Mediated Autophagy
Authors: Ferraresi Alessandra , Esposito Andrea , Girone Carlo , Vallino Letizia , Salwa Amreen , Ghezzi Ian , Thongchot Suyanee , Vidoni Chiara , Dhanasekaran Danny N. , Isidoro Ciro
Published: November 2021

Background: Ovarian cancer progression and invasiveness are promoted by a range of soluble factors released by cancer cells and stromal cells within the tumor microenvironment. Our previous studies demonstrated that resveratrol (RV), a nutraceutical and caloric restriction mimetic with tumor-suppressive properties, counteracts cancer cell motility induced by stromal IL-6 by upregulating autophagy. Lysophosphatidic acid (LPA), a bioactive phospholipid that shows elevated levels in the tumor microenvironment and the ascites of ovarian cancers, stimulates the growth and tissue invasion of cancer cells. Whether LPA elicits these effects by inhibiting autophagy and through which pathway and whether RV can counteract the same remain obscure. Aims: To investigate the molecular pathways involved in LPA-induced ovarian cancer malignancy, particularly focusing on the role of autophagy, and the ability of RV to counteract LPA activity. Results: LPA stimulated while RV inhibited ovarian cancer cell migration. Transcriptomic and bioinformatic analyses showed an opposite regulation by LPA and RV of genes linked to epithelial-to-mesenchymal transition (EMT) and autophagy with involvement of the PI3K-AKT, JAK-STAT and Hedgehog (Hh) pathways. LPA upregulated the Hh and EMT members GLI1, BMI-1, SNAIL-1 and TWIST1 and inhibited autophagy, while RV did the opposite. Similar to the inhibitors of the Hh pathway, RV inhibited LPA-induced cancer cell migration and 3D growth of ovarian cancer cells. BMI-1 silencing prevented LPA-induced EMT, restored autophagy and hampered cell migration, resembling the effects of RV. TCGA data analyses indicated that patients with low expression of Hh/EMT-related genes together with active autophagy flux tended to have a better prognosis and this correlates with a more effective response to platinum therapy. In in vitro 3D spheroids, LPA upregulated BMI-1, downregulated autophagy and inhibited platinum toxicity while RV and Hh inhibitors restored autophagy and favored BAX-mediated cell death in response to platinum. Conclusions: By inhibiting the Hh pathway and restoration of autophagy, RV counteracts LPA-induced malignancy, supporting its inclusion in the therapy of ovarian cancer for limiting metastasis and chemoresistance.
Electrophysiological Consequences of Cardiac Fibrosis
Authors: Verheule Sander , Schotten Ulrich
Published: November 2021

For both the atria and ventricles, fibrosis is generally recognized as one of the key determinants of conduction disturbances. By definition, fibrosis refers to an increased amount of fibrous tissue. However, fibrosis is not a singular entity. Various forms can be distinguished, that differ in distribution: replacement fibrosis, endomysial and perimysial fibrosis, and perivascular, endocardial, and epicardial fibrosis. These different forms typically result from diverging pathophysiological mechanisms and can have different consequences for conduction. The impact of fibrosis on propagation depends on exactly how the patterns of electrical connections between myocytes are altered. We will therefore first consider the normal patterns of electrical connections and their regional diversity as determinants of propagation. Subsequently, we will summarize current knowledge on how different forms of fibrosis lead to a loss of electrical connectivity in order to explain their effects on propagation and mechanisms of arrhythmogenesis, including ectopy, reentry, and alternans. Finally, we will discuss a histological quantification of fibrosis. Because of the different forms of fibrosis and their diverging effects on electrical propagation, the total amount of fibrosis is a poor indicator for the effect on conduction. Ideally, an assessment of cardiac fibrosis should exclude fibrous tissue that does not affect conduction and differentiate between the various types that do; in this article, we highlight practical solutions for histological analysis that meet these requirements.
Amniotic Epithelial Stem Cells Counteract Acidic Degradation By-Products of Electrospun PLGA Scaffold by Improving Their Immunomodulatory Profile In Vitro
Authors: El Khatib Mohammad , Russo Valentina , Prencipe Giuseppe , Mauro Annunziata , Wyrwa Ralf , Grimm Gabriele , Di Mattia Miriam , Berardinelli Paolo , Schnabelrauch Matthias , Barboni Barbara
Published: November 2021

Electrospun poly(lactic-co-glycolic acid) (PLGA) scaffolds with highly aligned fibers (ha-PLGA) represent promising materials in the field of tendon tissue engineering (TE) due to their characteristics in mimicking fibrous extracellular matrix (ECM) of tendon native tissue. Among these properties, scaffold biodegradability must be controlled allowing its replacement by a neo-formed native tendon tissue in a controlled manner. In this study, ha-PLGA were subjected to hydrolytic degradation up to 20 weeks, under di-H2O and PBS conditions according to ISO 10993-13:2010. These were then characterized for their physical, morphological, and mechanical features. In vitro cytotoxicity tests were conducted on ovine amniotic epithelial stem cells (oAECs), up to 7 days, to assess the effect of non-buffered and buffered PLGA by-products at different concentrations on cell viability and their stimuli on oAECs’ immunomodulatory properties. The ha-PLGA scaffolds degraded slowly as evidenced by a slight decrease in mass loss (14%) and average molecular weight (35%), with estimated degradation half-time of about 40 weeks under di-H2O. The ultrastructure morphology of the scaffolds showed no significant fiber degradation even after 20 weeks, but alteration of fiber alignment was already evident at week 1. Moreover, mechanical properties decreased throughout the degradation times under wet as well as dry PBS conditions. The influence of acid degradation media on oAECs was dose-dependent, with a considerable effect at 7 days’ culture point. This effect was notably reduced by using buffered media. To a certain level, cells were able to compensate the generated inflammation-like microenvironment by upregulating IL-10 gene expression and favoring an anti-inflammatory rather than pro-inflammatory response. These in vitro results are essential to better understand the degradation behavior of ha-PLGA in vivo and the effect of their degradation by-products on affecting cell performance. Indeed, buffering the degradation milieu could represent a promising strategy to balance scaffold degradation. These findings give good hope with reference to the in vivo condition characterized by physiological buffering systems.
Next- and Third-Generation Sequencing Outperforms Culture-Based Methods in the Diagnosis of Ascitic Fluid Bacterial Infections of ICU Patients
Authors: Goelz Hanna , Wetzel Simon , Mehrbarzin Negin , Utzolino Stefan , Häcker Georg , Badr Mohamed Tarek
Published: November 2021

Objectives: Infections of the ascitic fluid are serious conditions that require rapid diagnosis and treatment. Ascites is often accompanied by other critical pathologies such as gastrointestinal bleeding and bowel perforation, and infection increases the risk of mortality in intensive care patients. Owing to a relatively low success rate of conventional culture methods in identifying the responsible pathogens, new methods may be helpful to guide antimicrobial therapy and to refine empirical regimens. Here, we aim to assess outcomes and to identify responsible pathogens in ascitic fluid infections, in order to improve patients’ care and to guide empirical therapy. Methods: Between October 2019 and March 2021, we prospectively collected 50 ascitic fluid samples from ICU patients with suspected infection. Beside standard culture-based microbiology methods, excess fluid underwent DNA isolation and was analyzed by next- and third-generation sequencing (NGS) methods. Results: NGS-based methods had higher sensitivity in detecting additional pathogenic bacteria such as E. faecalis and Klebsiella in 33 out of 50 (66%) ascitic fluid samples compared with culture-based methods (26%). Anaerobic bacteria were especially identified by sequencing-based methods in 28 samples (56%), in comparison with only three samples in culture. Analysis of clinical data showed a correlation between sequencing results and various clinical parameters such as peritonitis and hospitalization outcomes. Conclusions: Our results show that, in ascitic fluid infections, NGS-based methods have a higher sensitivity for the identification of clinically relevant pathogens than standard microbiological culture diagnostics, especially in detecting hard-to-culture anaerobic bacteria. Patients with such infections may benefit from the use of NGS methods by the possibility of earlier and better targeted antimicrobial therapy, which has the potential to lower the high morbidity and mortality in critically ill patients with ascitic bacterial infection.
Challenges of Managing Information Security during the Pandemic
Authors: Mannebäck Emelie , Padyab Ali
Published: November 2021

The COVID-19 pandemic of 2019 surprised information security practitioners in the organizations due to the change imposed on employees’ work routines. Employees were asked to work from home, and therefore changes were necessary to reduce information security risks actively. The abrupt change of work environments brought many challenges to the practitioners, which caused them to make decisions regarding organizational information security. This article aims to uncover those challenges through an ethnography study within an organization during the fourteen months of teleworking. On an overarching level, we found four challenges to be of concern: technical security, regulations and policies, employee awareness of security issues, and, finally, preparedness for the new work environment of teleworking. We believe that the challenges brought by the analysis will inspire discussions about the future of research and practice regarding information security management in case of disasters.