bluuebunny/crossref_metadata_2025 huggingface dataset:
Cortical Correlates of Impulsive Aggressive Behavior in Pediatric Bipolar Disorder
Authors: Simonetti Alessio , Kurian Sherin , Saxena Johanna , Verrico Christopher D. , Restaino Antonio , Di Nicola Marco , Soares Jair C. , Sani Gabriele , Saxena Kirti
Published: July 2021

Background: Impulsive aggression represents a frequent characteristic of pediatric bipolar disorder (PBD). Cortical alterations associated with impulsive aggression and its multiple facets have not been investigated yet in youth with bipolar disorder.

Aim: To investigate the relationship between cortical thickness and facets of impulsive aggression in youth with PBD.

Materials and Methods: Twenty-three youth with PBD and 23 healthy controls (HC) were administered the aggression questionnaire (AQ) and underwent 3T magnetic resonance imaging scan. Cortical thickness was assessed with FreeSurfer. Canonical correlation analyses were used to investigate the relationship between AQ total and subscale scores and cortical thickness in youth with PBD.

Results: Youth with PBD had increased scores in the subscales of AQ-anger and AQ-hostility and cortical thinning in in areas belonging to the affective network (AN), frontoparietal network (FPN) and cingulo-opercular network (CON), i.e., right rostral anterior cingulate, right caudal anterior cingulate, right lateral orbitofrontal, right medial orbitofrontal, left and right inferior parietal, left posterior cingulate, left and right supramarginal left lingual cortices. Greater thickness in these networks positively correlated with the AQ-hostility subscale and negatively correlated with AQ-anger subscale.

Conclusions: The opposite patterns observed between areas belonging to AN, FPN, CON, and the two facets of IA, namely anger and hostility, corroborate clinical findings supporting the different nature of these two constructs.
Investigating the Links Between Vaccination Against COVID-19 and Public Attitudes Toward Protective Countermeasures: Implications for Public Health
Authors: Si Ruishi , Yao Yumeng , Zhang Xueqian , Lu Qian , Aziz Noshaba
Published: July 2021

The COVID-19 pandemic caused by the novel coronavirus, SARS-CoV-2, is spreading globally at an unprecedented rate. To protect the world against this devastating catastrophe, vaccines for SARS-CoV-2 have been produced following consistent clinical trials. However, the durability of a protective immune response due to vaccination has not been confirmed. Moreover, COVID-19 vaccination against SARS-CoV-2 is not 100% guaranteed, as new variants arise due to mutations. Consequently, health officials are pleading with the public to take extra precautions against the virus and continue wearing masks, wash hands, and observe physical distancing even after vaccination. The current research collected data from 4,540 participants (1,825 vaccinated and 2,715 not vaccinated) in China to analyze this phenomenon empirically. The propensity score matching (PSM) model is employed to analyze the impact of vaccination against COVID-19 on participants' attitudes toward protective countermeasures. The findings showed that gender, age, education level, occupation risk, individual health risk perception, public health risk perception, social responsibility, peer effect, and government supervision are the main drivers for participants to be vaccinated with COVID-19's vaccines. The results further show that vaccination lessened participants' frequency of hand washing by 1.75 times and their compliance frequency intensity of observing physical distancing by 1.24 times. However, the rate of mask-wearing did not reduce significantly, implying that China's main countermeasure of effective mask-wearing effectively controls COVID-19. Moreover, the findings indicate that a reduction in the frequency of hand washing and observing physical distance could cause a resurgence of COVID-19. In conclusion, factors leading to the eradication of SARS-CoV-2 from the world are complex to be achieved, so the exploration of COVID-19 vaccination and people's attitude toward protective countermeasures may provide insights for policymakers to encourage vaccinated people to follow protective health measures and help in completely defeating the COVID-19 from the globe.
Climate Change Impact on the Magnitude and Timing of Hydrological Extremes Across Great Britain
Authors: Lane Rosanna A. , Kay Alison L.
Published: July 2021

Climate change could intensify hydrological extremes, changing not just the magnitude but also the timing of flood and drought events. Understanding these potential future changes to hydrological extremes at the national level is critical to guide policy decisions and ensure adequate adaptation measures are put in place. Here, climate change impact on the magnitude and timing of extreme flows is modelled across Great Britain (GB), using an ensemble of climate data from the latest UK Climate Projections product (UKCP18) and a national grid-based hydrological model. All ensemble members show large reductions in low flows, of around −90 to −25% for 10-year return period low flows by 2050–2080. The direction of change for high flows is uncertain, but increases in 10-year return period high flows of over 9% are possible across most of the country. Simultaneous worsening of both extremes (i.e., a reduction in low flows combined with an increase in high flows) are projected in the west. Changes to flow timing are also projected; with mostly earlier annual maximum flows across Scotland, later annual maximum flows across England and Wales, and later low flows across GB. However, these changes are generally not statistically significant due to the high interannual variability of annual maximum/minimum flow timing. These results highlight the need for adaptation strategies that can cope with a wide range of future changes in hydrological extremes, and consider changes in the timing as well as magnitude.
Intraluminal Monitoring of Micro Vessels. A Surgical Feasibility Study
Authors: Walle Leonard , Sudhoff Holger , Frerichs Onno , Todt Ingo
Published: July 2021

Objective: Monitoring of vessel perfusion is of high clinical importance in vascular anastomosis of free flaps. Current sensor systems are based on different principles and show limitations in validity and accuracy. Fiber optic pressure sensors exhibit high accuracy and are small in size. The aim of the present study was to evaluate the surgical feasibility of intraluminal pressure (ILP) measurements with a fiber optic pressure sensor in an animal model.

Methods: In a microsurgical setting we sedated 10 Wistar rats with weight adapted phenobarbital, xylazine, and fentanyl. We performed a surgical approach to A. carotis communis and V. jugularis and introduced a 600 μm fiber optic pressure sensor into the vessels followed by measuring the ILP. The sensor was stabilized by the surrounding tissue, and the vessels were closed.

Results: In all cases, surgical placement was uneventful. Measurement of intra-venous and intra-arterial pressure was possible and stable over the whole measurement period of an hour.

Conclusion: Fiber optic pressure measurement in microvessels is possible and surgically feasible. An application to monitor the perfusion of free flaps seems possible.
Enhanced Recovery After Surgery for Patients Undergoing Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy: A Systematic Review and Meta-Analysis
Authors: Mao Feng , Huang Zhenmin
Published: July 2021

Background: Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) is a promising approach for the management of peritoneal carcinomatosis, but is associated with significant morbidity and prolonged hospital stay. Herein, we review the impact of Enhanced recovery after surgery (ERAS) protocol on length of stay (LOS) and early complications in patients undergoing CRS and HIPEC for peritoneal carcinomatosis.

Methods: PubMed and Embase were searched for studies comparing ERAS protocol with control for CRS + HIPEC. Mean difference (MD) and risk ratios (RR) were calculated for LOS and complications respectively.

Results: Six retrospective studies were included. Meta-analysis indicated statistically significant reduction in LOS with ERAS (MD: −2.82 95% CI: −3.79, −1.85 I2 = 29% p < 0.00001). Our results demonstrated significantly reduced risk of Calvien Dindo grade III/IV complications with the use of ERAS protocol as compared to the control group (RR: 0.60 95% CI: 0.41, 0.87 I2 = 0% p = 0.007). Pooled analysis of limited studies demonstrated no statistically significant difference in the risk of reoperation (RR: 1.04 95% CI: 0.54, 2.03 I2 = 50% p = 0.90) readmission (RR: 0.55 95% CI: 0.21, 1.49 I2 = 0% p = 0.24), acute kidney injury (RR: 0.55 95% CI: 0.28, 1.10 I2 = 0% p = 0.09) or mortality (RR: 0.62 95% CI: 0.17, 2.26 I2 = 0% p = 0.46) between the study groups.

Conclusion: For CRS + HIPEC, ERAS is associated with significantly reduced LOS along with lower incidence of complications. Limited data suggest that use of ERAS protocol is not associated with increased readmission, reoperation, and mortality rates in these patients. There is a need for randomized controlled trials to corroborate the current evidence.
Dietary Yucca schidigera Extract Supplementation During Late Gestating and Lactating Sows Improves Animal Performance, Nutrient Digestibility, and Manure Ammonia Emission
Authors: Chen Fang , Lv Yantao , Zhu Pengwei , Cui Chang , Wu Caichi , Chen Jun , Zhang Shihai , Guan Wutai
Published: July 2021

This study was conducted to investigate the effect of dietary Yucca schidigera extract (YSE) supplementation to sow performance, nutrients digestibility and ammonia emission of manure. Total 80 sows were randomly divided into 4 groups and fed with either control, control + 0.06% YSE, control + 0.12% YSE or control + 0.24% YSE diet from day 80 of gestation to day 21 of lactation. The results showed that dietary YSE supplementation resulted in trends toward a reduced number of stillbirth piglets (P = 0.08), weak piglets (P = 0.06), pre-weanling mortality (P = 0.04) and diarrhea (P = 0.03), and improved apparent digestibility of dry matter (P = 0.04). Besides, YSE supplementation significantly increased catalase activity (P = 0.02) while decreasing malonaldehyde levels (P = 0.04) in sow blood. Furthermore, the loss of total nitrogen, urea nitrogen and ammonia nitrogen in sow manure were significantly reduced with supplementation of YSE. In summary, supplementation of YSE in sow diet during late gestation and lactation could improve sow and litter performance, nutrient digestibility, and reduce nitrogen loss in sow manure during storage.
Mutation Profiles of eGFP-Tagged Small Ruminant Morbillivirus During 45 Serial Passages in Ribavirin-Treated Cells
Authors: Liu Fuxiao , Zou Yanli , Li Lin , Liu Chunju , Wu Xiaodong
Published: July 2021

Small ruminant morbillivirus (SRMV), formerly known as peste-des-petits-ruminants virus, classified into the genus Morbillivirus in the family Paramyxoviridae. Its L protein functions as the RNA-dependent RNA polymerases (RdRp) during viral replication. Due to the absence of efficient proofreading activity in their RdRps, various RNA viruses reveal high mutation frequencies, making them evolve rapidly during serial passages in cells, especially treated with a certain mutagen, like ribavirin. We have previously rescued a recombinant enhanced green fluorescence protein-tagged SRMV (rSRMV-eGFP) using reverse genetics. In this study, the rSRMV-eGFP was subjected to serial passages in ribavirin-treated cells. Due to the ribavirin-exerted selective pressure, it was speculated that viral progenies would form quasispecies after dozens of passages. Viral progenies at passage-10, -20, -30, -40, and -50 were separately subjected to next-generation sequencing (NGS), consequently revealing a total of 34 single-nucleotide variations, including five synonymous, 21 missense, and one non-sense mutations. The L sequence was found to harbor eight missense mutations during serial passaging. It was speculated that at least one high-fidelity variant was present in viral quasispecies at passage-50. If purified from the population of viral progenies, this putative variant would contribute to clarifying a molecular mechanism in viral high-fidelity replication in vitro.
Multi-Input Deep Learning Model with RGB and Hyperspectral Imaging for Banana Grading
Authors: Mesa Armacheska Rivero , Chiang John Y.
Published: July 2021

Grading is a vital process during the postharvest of horticultural products as it dramatically affects consumer preference and satisfaction when goods reach the market. Manual grading is time-consuming, uneconomical, and potentially destructive. A non-invasive automated system for export-quality banana tiers was developed, which utilized RGB, hyperspectral imaging, and deep learning techniques. A real dataset of pre-classified banana tiers based on quality and size (Class 1 for export quality bananas, Class 2 for the local market, and Class 3 for defective fruits) was utilized using international standards. The multi-input model achieved an excellent overall accuracy of 98.45% using only a minimal number of samples compared to other methods in the literature. The model was able to incorporate both external and internal properties of the fruit. The size of the banana was used as a feature for grade classification as well as other morphological features using RGB imaging, while reflectance values that offer valuable information and have shown a high correlation with the internal features of fruits were obtained through hyperspectral imaging. This study highlighted the combined strengths of RGB and hyperspectral imaging in grading bananas, and this can serve as a paradigm for grading other horticultural crops. The fast-processing time of the multi-input model developed can be advantageous when it comes to actual farm postharvest processes.
β-Hydroxybutyrate, a Ketone Body, Potentiates the Antioxidant Defense via Thioredoxin 1 Upregulation in Cardiomyocytes
Authors: Oka Shin-ichi , Tang Fan , Chin Adave , Ralda Guersom , Xu Xiaoyong , Hu Chengchen , Yang Zhi , Abdellatif Maha , Sadoshima Junichi
Published: July 2021

Thioredoxin 1 (Trx1) is a major antioxidant that acts adaptively to protect the heart during the development of diabetic cardiomyopathy. The molecular mechanism(s) responsible for regulating the Trx1 level and/or activity during diabetic cardiomyopathy is unknown. β-hydroxybutyrate (βHB), a major ketone body in mammals, acts as an alternative energy source in cardiomyocytes under stress, but it also appears to be involved in additional mechanisms that protect the heart against stress. βHB upregulated Trx1 in primary cultured cardiomyocytes in a dose- and a time-dependent manner and a ketogenic diet upregulated Trx1 in the heart. βHB protected cardiomyocytes against H2O2-induced death, an effect that was abolished in the presence of Trx1 knockdown. βHB also alleviated the H2O2-induced inhibition of mTOR and AMPK, known targets of Trx1, in a Trx1-dependent manner, suggesting that βHB potentiates Trx1 function. It has been shown that βHB is a natural inhibitor of HDAC1 and knockdown of HDAC1 upregulated Trx1 in cardiomyocytes, suggesting that βHB may upregulate Trx1 through HDAC inhibition. βHB induced Trx1 acetylation and inhibited Trx1 degradation, suggesting that βHB-induced inhibition of HDAC1 may stabilize Trx1 through protein acetylation. These results suggest that βHB potentiates the antioxidant defense in cardiomyocytes through the inhibition of HDAC1 and the increased acetylation and consequent stabilization of Trx1. Thus, modest upregulation of ketone bodies in diabetic hearts may protect the heart through the upregulation of Trx1.
Diabetic Embryopathy Susceptibility in Mice Is Associated with Differential Dependence on Glucosamine and Modulation of High Glucose-Induced Oxidative Stress
Authors: Jung Jin Hyuk , Loeken Mary R.
Published: July 2021

The high KM glucose transporter, GLUT2 (SLC2A2), is expressed by embryos and causes high rates of glucose transport during maternal hyperglycemic episodes in diabetic pregnancies and causes congenital malformations (diabetic embryopathy). GLUT2 is also a low KM transporter of the amino sugar, glucosamine (GlcN), which enters the hexosamine biosynthetic pathway (HBP) and provides substrate for glycosylation reactions. Exogenous GlcN also increases activity of the pentose phosphate pathway (PPP), which increases production of NADPH reducing equivalents. GLUT2-transported GlcN is inhibited by high glucose concentrations. Not all mouse strains are susceptible to diabetic embryopathy. The aim of this study was to test the hypothesis that susceptibility to diabetic embryopathy is related to differential dependence on exogenous GlcN for glycosylation or stimulation of the PPP. We tested this using murine embryonic stem cell (ESC) lines that were derived from embryopathy-susceptible FVB/NJ (FVB), and embryopathy-resistant C57Bl/6J (B6), embryos in the presence of low or high glucose, and in the presence or absence of GlcN. There were no significant differences in Glut2 expression, or of glucose or GlcN transport, between FVB and B6 ESC. GlcN effects on growth and incorporation into glycoproteins indicated that FVB ESC are more dependent on exogenous GlcN than are B6 ESC. GlcN stimulated PPP activity in FVB but not in B6 ESC. High glucose induced oxidative stress in FVB ESC but not in B6 ESC. These results indicate that FVB embryos are more dependent on exogenous GlcN for glycosylation, but also for stimulation of the PPP and NADPH production, than are B6 embryos, thereby rendering FVB embryos more susceptible to high glucose to induce oxidative stress.
Changes in Hepatic Phospholipid Metabolism in Rats under UV Irradiation and Topically Treated with Cannabidiol
Authors: Biernacki Michał , Jastrząb Anna , Skrzydlewska Elżbieta
Published: July 2021

The liver is a key metabolic organ that is particularly sensitive to environmental factors, including UV radiation. As UV radiation induces oxidative stress and inflammation, natural compounds are under investigation as one method to counteract these consequences. The aim of this study was to assess the effect of topical application of phytocannabinoid-cannabidiol (CBD) on the skin of nude rats chronically irradiated with UVA/UVB, paying particular attention to its impact on the liver antioxidants and phospholipid metabolism. The results of this study indicate that CBD reaches the rat liver where it is then metabolized into decarbonylated cannabidiol, 7-hydroxy-cannabidiol and cannabidiol-glucuronide. CBD increased the levels of GSH and vitamin A after UVB radiation. Moreover, CBD prevents the increase of 4-hydroxynonenal and 8-iso-prostaglandin-F2α levels in UVA-irradiated rats. As a consequence of reductions in phospholipase A2 and cyclooxygenases activity following UV irradiation, CBD upregulates the level of 2-arachidonoylglycerol and downregulates prostaglandin E2 and leukotriene B4. Finally, CBD enhances decreased level of 15-deoxy-Δ-12,14-prostaglandin J2 after UVB radiation and 15-hydroxyeicosatetraenoic acid after UVA radiation. These data show that CBD applied to the skin prevents ROS- and enzyme-dependent phospholipid metabolism in the liver of UV-irradiated rats, suggesting that it may be used as an internal organ protector.
The Genetic Regulation of Secondary Metabolic Pathways in Response to Salinity and Drought as Abiotic Stresses
Authors: Qari Sameer Hasan , Tarbiyyah Ibrahim
Published: July 2021

Global development has generated a plethora of unfavorable and adverse environmental factors for the living organisms in the ecosystem. Plants are sessile organisms, and they are crucial to sustain life on earth. Since plants are sessile, they face a great number of environmental challenges related to abiotic stresses, such as temperature fluctuation, drought, salinity, flood and metal contamination. Salinity and drought are considered major abiotic stresses that negatively affect the plants’ growth and production of useful content. However, plants have evolved various molecular mechanisms to increase their tolerance to these environmental stresses. There is a whole complex system of communication (cross-talk) through massive signaling cascades that are activated and modulated in response to salinity and drought. Secondary metabolites are believed to play significant roles in the plant’s response and resistance to salinity and drought stress. Until recently, attempts to unravel the biosynthetic pathways were limited mainly due to the inadequate plant genomics resources. However, recent advancements in generating high-throughput “omics” datasets, computational tools and functional genomics approach integration have aided in the elucidation of biosynthetic pathways of many plant bioactive metabolites. This review gathers comprehensive knowledge of plants’ complex system that is involved in the response and resistance to salinity and water deficit stresses as abiotic stress. Additionally, it offers clues in determining the genes involved in this complex and measures its activity. It covers basic information regarding the signaling molecules involved in salinity and drought resistance and how plant hormones regulate the cross-talking mechanism with emphasis on transcriptional activity. Moreover, it discusses many studies that illustrate the relationship between salinity and drought and secondary metabolite production. Furthermore, several transcriptome analysis research papers of medicinal plants are illustrated. The aim of this review is to be a key for any researcher that is aspiring to study the relationship between salinity and drought stresses and secondary metabolite production at the transcriptome and transcription level.
Lactobacillus plantarum SK15 as a Starter Culture for Prevention of Biogenic Amine Accumulation in Fermented Beverage Containing Hericium erinaceus Mushroom
Authors: Makhamrueang Netnapa , Sirilun Sasithorn , Sirithunyalug Jakkapan , Chaiyana Wantida , Wangcharoen Wiwat , Peerajan Sartjin , Chaiyasut Chaiyavat
Published: July 2021

The effectiveness of Lactobacillus plantarum SK15 starter culture in preventing biogenic amine production, such as putrescine (PUT) and spermidine (SPD), during the fermented mushroom beverage (FMB) process using Hericium erinaceus was examined. Spontaneously fermented and starter-mediated FMB was manufactured in parallel. Besides changes in pH, total acidity content, alcohol content, amino acid content, reducing sugar content, total phenolic content, antioxidant activity, and the microbial load were examined at several sampling points during the 720-h fermentation process. As a result, the L. plantarum SK15 starter prevented biogenic amine accumulation during FMB fermentation. Moreover, starter-mediated FMB can control pH and alcohol content at an acceptable level. In addition, FMB with L. plantarum SK15 had a higher level of total phenolic content (TPC) and antioxidant activity.
Traffic Accident Risk Assessment Framework for Qassim, Saudi Arabia: Evaluating the Impact of Speed Cameras
Authors: Almoshaogeh Meshal , Abdulrehman Radfan , Haider Husnain , Alharbi Fawaz , Jamal Arshad , Alarifi Saif , Shafiquzzaman Md.
Published: July 2021

Saudi Arabia is one of the countries with the highest number of road accidents and associated fatalities in the world. Speeding has been identified as an important cause of increased traffic accidents, which also aggravate their severity. Road safety improvement strategies are primarily based on the accurate identification of accident hotspots. Installing speed cameras at a network level is an expensive road safety measure, and its spatiotemporal effectiveness should be assessed. In this study, a traffic accident risk assessment framework has been developed and implemented on the 84 km long Buraydah Ring Road in the Qassim region of Saudi Arabia. The selected highway was divided into 42 (×2 km long) segments using the ArcGIS software. A risk scoring scheme was developed to incorporate both the frequency and severity of road accidents. Speed cameras installation at various segments showed a 70% decline in total accident counts, 53% in accidents with property damage, 84% decline in accidents causing injury, and complete absence of accidents with fatalities. The 48% segments were identified as hotspots with risk level ≥ medium, while the speed cameras installation completely eliminated the hotspots from the study area. The proposed framework can be implemented on major high-speed highways, accommodating high traffic volumes, for hotspot identification and evaluation of various road safety measures in Saudi Arabia and elsewhere.
Kernel-Based Phase Transfer Entropy with Enhanced Feature Relevance Analysis for Brain Computer Interfaces
Authors: De La Pava Panche Iván , Álvarez-Meza Andrés , Herrera Gómez Paula Marcela , Cárdenas-Peña David , Ríos Patiño Jorge Iván , Orozco-Gutiérrez Álvaro
Published: July 2021

Neural oscillations are present in the brain at different spatial and temporal scales, and they are linked to several cognitive functions. Furthermore, the information carried by their phases is fundamental for the coordination of anatomically distributed processing in the brain. The concept of phase transfer entropy refers to an information theory-based measure of directed connectivity among neural oscillations that allows studying such distributed processes. Phase TE is commonly obtained from probability estimations carried out over data from multiple trials, which bars its use as a characterization strategy in brain–computer interfaces. In this work, we propose a novel methodology to estimate TE between single pairs of instantaneous phase time series. Our approach combines a kernel-based TE estimator defined in terms of Renyi’s α entropy, which sidesteps the need for probability distribution computation with phase time series obtained by complex filtering the neural signals. Besides, a kernel-alignment-based relevance analysis is added to highlight relevant features from effective connectivity-based representation supporting further classification stages in EEG-based brain–computer interface systems. Our proposal is tested on simulated coupled data and two publicly available databases containing EEG signals recorded under motor imagery and visual working memory paradigms. Attained results demonstrate how the introduced effective connectivity succeeds in detecting the interactions present in the data for the former, with statistically significant results around the frequencies of interest. It also reflects differences in coupling strength, is robust to realistic noise and signal mixing levels, and captures bidirectional interactions of localized frequency content. Obtained results for the motor imagery and working memory databases show that our approach, combined with the relevance analysis strategy, codes discriminant spatial and frequency-dependent patterns for the different conditions in each experimental paradigm, with classification performances that do well in comparison with those of alternative methods of similar nature.
In Vitro Evaluation of Cytotoxicity and Proliferative Effects of Lyophilized Porcine Liver Tissue on HepG2 Hepatoma Cells and Adipose-Tissue-Derived Mesenchymal Stromal Cells
Authors: Berni Priscilla , Conti Virna , Ferroni Orlando , Ramoni Roberto , Basini Giuseppina , Grolli Stefano
Published: July 2021

In recent years, nutritional supplements from different sources have been widely considered to support medical treatments in patients affected by chronic hepatopathies. Their potential therapeutic benefit has been recognized, but some evidence of safety issues has been reported. Recently it has been hypothesized that the liver could produce various of bioactive factors to maintain organ homeostasis and promote tissue healing. Thus, liver-specific preparations containing bioactive factors could provide a suitable substrate for in vitro study of liver tissue maintenance/healing, as a prospective regenerative medicine approach. Furthermore, they could represent a dietary supplement or nutraceutical for adjuvant therapies when correctly prepared and formulated. This work aims to provide data about the safety and biological activity of a freeze-dried porcine liver preparation. The lyophilized powder obtained from the whole organ has been tested in term of in vitro cell cytotoxicity (MTT assay) and proliferation assays (bromo-deoxyuridine incorporation and direct cell count) in two different cell types: human hepatoma HepG2 cell line and adipose-tissue-derived canine mesenchymal stromal cells (At-MSCs). At concentration levels between 100 to 500 µg/mL, the lyophilized liver powder stimulated mitochondrial metabolism as assessed by MTT assay (p ≤ 0.001 for HepG2 and for At-MSCs) and induced an increase in bromo-deoxyuridine incorporation in both cell types (p ≤ 0.01 for HepG2 and p < 0.001 for At-MSCs). In addition, direct cell count demonstrated a higher proliferative activity in treated At-MSCs (p < 0.001). Although preliminary, these data suggest that the whole-liver powder is noncytotoxic in vitro and may represent a stimulus to cell metabolism and proliferation. Further studies are needed to detect the bioactive components of the supplement and characterize in deeper detail the cellular pathways that they can modulate.
Functional Interactions between Entorhinal Cortical Pathways Modulate Theta Activity in the Hippocampus
Authors: López-Madrona Víctor J. , Canals Santiago
Published: July 2021

Theta oscillations organize neuronal firing in the hippocampus during context exploration and memory formation. Recently, we have shown that multiple theta rhythms coexist in the hippocampus, reflecting the activity in their afferent regions in CA3 (Schaffer collaterals) and the entorhinal cortex layers II (EC-II, perforant pathway) and III (EC-III, temporoammonic pathway). Frequency and phase coupling between theta rhythms were modulated by the behavioral state, with synchronized theta rhythmicity preferentially occurring in tasks involving memory updating. However, information transmission between theta generators was not investigated. Here, we used source separation techniques to disentangle the current generators recorded in the hippocampus of rats exploring a known environment with or without a novel stimulus. We applied analytical tools based on Granger causality and transfer entropy to investigate linear and non-linear directed interactions, respectively, between the theta activities. Exploration in the novelty condition was associated with increased theta power in the generators with EC origin. We found a significant directed interaction from the Schaffer input over the EC-III input in CA1, and a bidirectional interaction between the inputs in the hippocampus originating in the EC, likely reflecting the connection between layers II and III. During novelty exploration, the influence of the EC-II over the EC-III generator increased, while the Schaffer influence decreased. These results associate the increase in hippocampal theta activity and synchrony during novelty exploration with an increase in the directed functional connectivity from EC-II to EC-III.
Do We Need to Use Bats as Bioindicators?
Authors: Russo Danilo , Salinas-Ramos Valeria B. , Cistrone Luca , Smeraldo Sonia , Bosso Luciano , Ancillotto Leonardo
Published: July 2021

Bats show responses to anthropogenic stressors linked to changes in other ecosystem components such as insects, and as K-selected mammals, exhibit fast population declines. This speciose, widespread mammal group shows an impressive trophic diversity and provides key ecosystem services. For these and other reasons, bats might act as suitable bioindicators in many environmental contexts. However, few studies have explicitly tested this potential, and in some cases, stating that bats are useful bioindicators more closely resembles a slogan to support conservation than a well-grounded piece of scientific evidence. Here, we review the available information and highlight the limitations that arise in using bats as bioindicators. Based on the limited number of studies available, the use of bats as bioindicators is highly promising and warrants further investigation in specific contexts such as river quality, urbanisation, farming practices, forestry, bioaccumulation, and climate change. Whether bats may also serve as surrogate taxa remains a controversial yet highly interesting matter. Some limitations to using bats as bioindicators include taxonomical issues, sampling problems, difficulties in associating responses with specific stressors, and geographically biased or delayed responses. Overall, we urge the scientific community to test bat responses to specific stressors in selected ecosystem types and develop research networks to explore the geographic consistency of such responses. The high cost of sampling equipment (ultrasound detectors) is being greatly reduced by technological advances, and the legal obligation to monitor bat populations already existing in many countries such as those in the EU offers an important opportunity to accomplish two objectives (conservation and bioindication) with one action.
Angiotensin II-Induced Vasoconstriction via Rho Kinase Activation in Pressure-Overloaded Rat Thoracic Aortas
Authors: Terada Yuka , Yayama Katsutoshi
Published: July 2021

Angiotensin II (Ang II) induces vasoconstriction through myosin light chain (MLC) kinase activation and MLC phosphatase inactivation via phosphorylation of myosin phosphatase targeting subunit 1 (MYPT1) by Rho kinase. However, the detailed mechanism underlying Rho kinase activation by Ang II is still unknown. We investigated the mechanism of Ang II-induced vasoconstriction mediated by Rho kinase in pressure-overloaded rat thoracic aortas. Pressure-overloaded rats were produced by coarctation of the suprarenal abdominal aorta in four-week-old male Wistar rats. The contractile response to Ang II was significantly enhanced in the pressure-overloaded rats. Ang II-induced vasoconstriction was attenuated by inhibitors of Rho kinase, extracellular signal-regulated kinase 1 and 2 (Erk1/2), and epidermal growth factor receptor (EGFR) in both the sham-operated and pressure-overloaded rats. The Ang II-induced vasoconstriction was attenuated by a Janus kinase 2 (JAK2) inhibitor in only the pressure-overloaded rats. The protein levels of MYPT1 and JAK2 increased only in the pressure-overloaded rat thoracic aortas. These results suggested that Ang II-induced contraction is mediated by Rho kinase activation via EGFR, Erk1/2, and JAK2 in pressure-overloaded rat thoracic aortas. Moreover, Ang II-induced contraction was enhanced in pressure-overloaded rats probably because the protein levels of MYPT1 and JAK2 increased in the thoracic aortas.
Mental Health in Childhood and Adolescence: The Role of Polyunsaturated Fatty Acids
Authors: Bozzatello Paola , Blua Cecilia , Rocca Paola , Bellino Silvio
Published: July 2021

There is increasing awareness of the importance of polyunsaturated fatty acids (PUFAs) for optimal brain development and function. In recent decades, researchers have confirmed the central role of PUFAs in a variety of patho-physiological processes. These agents modulate the mechanisms of brain cell signalling including the dopaminergic and serotonergic pathways. Therefore, nutritional insufficiencies of PUFAs may have adverse effects on brain development and developmental outcomes. The role of n-3 PUFAs has been studied in several psychiatric disorders in adulthood: schizophrenia, major depression, bipolar disorder, anxiety disorders, obsessive-compulsive disorder, post-traumatic stress disorder, attention deficit hyperactivity disorder (ADHD), autism spectrum disorders, eating disorders, substance use disorder, and borderline personality disorder. In contrast to the great number of studies conducted in adults, there are only limited data on the effects of n-3 PUFA supplementation in children and adolescents who suffer from mental disorders or show a high risk of developing psychiatric disorders. The aim of this review is to provide a complete and updated account of the available evidence of the impact of polyunsaturated fatty acids on developmental psychopathology in children and adolescents and the effect of fatty acid supplementation during developmental milestones, particularly in high-risk populations of children with minimal but detectable signs or symptoms of mental disorders.
Local Delivery of Pirfenidone by PLA Implants Modifies Foreign Body Reaction and Prevents Fibrosis
Authors: Fayzullin Alexey , Churbanov Semyon , Ignatieva Natalia , Zakharkina Olga , Tokarev Mark , Mudryak Daniil , Khristidis Yana , Balyasin Maxim , Kurkov Alexandr , Golubeva Elena N. , Aksenova Nadejda A. , Dyuzheva Tatyana , Timashev Peter , Guller Anna , Shekhter Anatoly
Published: July 2021

Peri-implant fibrosis (PIF) increases the postsurgical risks after implantation and limits the efficacy of the implantable drug delivery systems (IDDS). Pirfenidone (PF) is an oral anti-fibrotic drug with a short (<3 h) circulation half-life and strong adverse side effects. In the current study, disk-shaped IDDS prototype combining polylactic acid (PLA) and PF, PLA@PF, with prolonged (~3 days) PF release (in vitro) was prepared. The effects of the PLA@PF implants on PIF were examined in the rabbit ear skin pocket model on postoperative days (POD) 30 and 60. Matching blank PLA implants (PLA0) and PLA0 with an equivalent single-dose PF injection performed on POD0 (PLA0+injPF) served as control. On POD30, the intergroup differences were observed in α-SMA, iNOS and arginase-1 expressions in PLA@PF and PLA0+injPF groups vs. PLA0. On POD60, PIF was significantly reduced in PLA@PF group. The peri-implant tissue thickness decreased (532 ± 98 μm vs. >1100 μm in control groups) approaching the intact derma thickness value (302 ± 15 μm). In PLA@PF group, the implant biodegradation developed faster, while arginase-1 expression was suppressed in comparison with other groups. This study proves the feasibility of the local control of fibrotic response on implants via modulation of foreign body reaction with slowly biodegradable PF-loaded IDDS.
Current Concepts in the Treatment of Giant Cell Tumors of Bone
Authors: Tsukamoto Shinji , Mavrogenis Andreas F. , Kido Akira , Errani Costantino
Published: July 2021

The 2020 World Health Organization classification defined giant cell tumors of bone (GCTBs) as intermediate malignant tumors. Since the mutated H3F3A was found to be a specific marker for GCTB, it has become very useful in diagnosing GCTB. Curettage is the most common treatment for GCTBs. Preoperative administration of denosumab makes curettage difficult and increases the risk of local recurrence. Curettage is recommended to achieve good functional outcomes, even for local recurrence. For pathological fractures, joints should be preserved as much as possible and curettage should be attempted. Preoperative administration of denosumab for pelvic and spinal GCTBs reduces extraosseous lesions, hardens the tumor, and facilitates en bloc resection. Nerve-sparing surgery after embolization is a possible treatment for sacral GCTBS. Denosumab therapy with or without embolization is indicated for inoperable pelvic, spinal, and sacral GCTBs. It is recommended to first observe lung metastases, then administer denosumab for growing lesions. Radiotherapy is associated with a risk of malignant transformation and should be limited to cases where surgery is impossible and denosumab, zoledronic acid, or embolization is not available. Local recurrence after 2 years or more should be indicative of malignant transformation. This review summarizes the treatment approaches for non-malignant and malignant GCTBs.
Collagen Organization Does Not Influence T-Cell Distribution in Stroma of Human Pancreatic Cancer
Authors: Kamionka Eva-Maria , Qian Baifeng , Gross Wolfgang , Bergmann Frank , Hackert Thilo , Beretta Carlo A. , Dross Nicolas , Ryschich Eduard
Published: July 2021

The dominant intrastromal T-cell infiltration in pancreatic cancer is mainly caused by the contact guidance through the excessive desmoplastic reaction and could represent one of the obstacles to an effective immune response in this tumor type. This study analyzed the collagen organization in normal and malignant pancreatic tissues as well as its influence on T-cell distribution in pancreatic cancer. Human pancreatic tissue was analyzed using immunofluorescence staining and multiphoton and SHG microscopy supported by multistep image processing. The influence of collagen alignment on activated T-cells was studied using 3D matrices and time-lapse microscopy. It was found that the stroma of malignant and normal pancreatic tissues was characterized by complex individual organization. T-cells were heterogeneously distributed in pancreatic cancer and there was no relationship between T-cell distribution and collagen organization. There was a difference in the angular orientation of collagen alignment in the peritumoral and tumor-cell-distant stroma regions in the pancreatic ductal adenocarcinoma tissue, but there was no correlation in the T-cell densities between these regions. The grade of collagen alignment did not influence the directionality of T-cell migration in the 3D collagen matrix. It can be concluded that differences in collagen organization do not change the spatial orientation of T-cell migration or influence stromal T-cell distribution in human pancreatic cancer. The results of the present study do not support the rationale of remodeling of stroma collagen organization for improvement of T-cell–tumor cell contact in pancreatic ductal adenocarcinoma.
Experimental Models of Hepatocellular Carcinoma—A Preclinical Perspective
Authors: Blidisel Alexandru , Marcovici Iasmina , Coricovac Dorina , Hut Florin , Dehelean Cristina Adriana , Cretu Octavian Marius
Published: July 2021

Hepatocellular carcinoma (HCC), the most frequent form of primary liver carcinoma, is a heterogenous and complex tumor type with increased incidence, poor prognosis, and high mortality. The actual therapeutic arsenal is narrow and poorly effective, rendering this disease a global health concern. Although considerable progress has been made in terms of understanding the pathogenesis, molecular mechanisms, genetics, and therapeutical approaches, several facets of human HCC remain undiscovered. A valuable and prompt approach to acquire further knowledge about the unrevealed aspects of HCC and novel therapeutic candidates is represented by the application of experimental models. Experimental models (in vivo and in vitro 2D and 3D models) are considered reliable tools to gather data for clinical usability. This review offers an overview of the currently available preclinical models frequently applied for the study of hepatocellular carcinoma in terms of initiation, development, and progression, as well as for the discovery of efficient treatments, highlighting the advantages and the limitations of each model. Furthermore, we also focus on the role played by computational studies (in silico models and artificial intelligence-based prediction models) as promising novel tools in liver cancer research.
Impact of Smoking-Related Chronic Obstruction Pulmonary Disease on Mortality of Invasive Ductal Carcinoma Patients Receiving Standard Treatments: Propensity Score-Matched, Nationwide, Population-Based Cohort Study
Authors: Zhang Jia-Qiang , Cheng Tsai-Mu , Lin Wei-Chun , Chiu Kuo-Chin , Wu Szu-Yuan
Published: July 2021

Purpose: the survival effect of smoking-related chronic obstructive pulmonary disease (COPD) and COPD with acute exacerbation (COPDAE) is unclear for patients with invasive ductal carcinoma (IDC) receiving standard treatments. Methods: we recruited women with clinical stage I–III IDC from the Taiwan Cancer Registry Database who had received standard treatments between 1 January 2009 and 31 December 2018. The time-dependent Cox proportional hazards model was used to analyze all-cause mortality. To reduce the effects of potential confounders when all-cause mortality between Groups 1 and 2 were compared, 1:2 propensity score matching (PSM) was performed. We categorized the patients into two groups based on COPD status to compare overall survival outcomes: Group 1 (current smokers with COPD) and Group 2 (nonsmokers without COPD group). Results: PSM yielded 2319 patients with stage I–III IDC (773 and 1546 in Groups 1 and 2, respectively) eligible for further analysis. In the multivariate time-dependent Cox regression analyses, the adjusted hazard ratio (aHR; 95% confidence interval (CI)) of all-cause mortality for Group 1 compared with Group 2 was 1.04 (0.83–1.22). The aHRs (95% CIs) of all-cause mortality for ≥1 hospitalization for COPDAE within one year before breast surgery was 1.51 (1.18–2.36) compared with no COPDAE. Conclusion: smoking-related COPD was not a significant independent risk factor for all-cause mortality in women with stage I–III IDC receiving standard treatments. Being hospitalized at least once for COPDAE within one year before breast surgery is highly associated with high mortality for women with IDC receiving standard treatments. The severity of smoking-related COPD before treatments for breast cancer might be an important prognostic factor of survival. Thus, the information of the severity of COPD before treatment for breast cancer might be valuable for increasing the survival rate in treatment of breast cancer, especially in the prevention of progress from COPD to COPDAE.
Effects of and Lessons Learned from an Internet-Based Physical Activity Support Program (with and without Physiotherapist Telephone Counselling) on Physical Activity Levels of Breast and Prostate Cancer Survivors: The PABLO Randomized Controlled Trial
Authors: van de Wiel H. J. , Stuiver M. M. , May A. M. , van Grinsven S. , Aaronson N. K. , Oldenburg H. S. A. , van der Poel H. G. , Koole S. N. , Retèl V. P. , van Harten W. H. , Groen W. G.
Published: July 2021

Background: We developed an Internet-based physical activity (PA) support program (IPAS), which is embedded in a patient portal. We evaluated the effectiveness and costs of IPAS alone (online only) or IPAS combined with physiotherapist telephone counselling (blended care), compared to a control group. Methods: Breast or prostate cancer survivors, 3–36 months after completing primary treatment, were randomized to 6-months access to online only, blended care, or a control group. At baseline and 6-month post-baseline, minutes of moderate-to-vigorous PA (MVPA) were measured by accelerometers. Secondary outcomes were self-reported PA, fatigue, mood, health-related quality of life, attitude toward PA, and costs. (Generalized) linear models were used to compare the outcomes between groups. Results: We recruited 137 survivors (participation rate 11%). We did not observe any significant between-group differences in MVPA or secondary outcomes. Adherence was rather low and satisfaction scores were low to moderate, with better scores for blended care. Costs for both interventions were low. Conclusions: Recruitment to the study was challenging and the interventions were less efficacious than anticipated, which led to lessons learned for future trials. Suggestions for future research are as follows: improved accessibility of the support program, increased frequency of support, and use of activity trackers.
Optimization of Calcination Conditions for Cu/ZnO/Al2O3-ZrO2 Catalyst
Authors: Zulkifli Nur Insyirah , Berahim Nor Hafizah , Mohd Zabidi Noor Asmawati , Tasfy Sara Faiz Hanna
Published: July 2021

Promoted Cu/ZnO catalyst was synthesized on Al2O3-ZrO2 support. Effects of calcination conditions on the catalytic performance in a CO2 hydrogenation reaction were studied systematically using the response surface methodology (RSM). The application of RSM with rotatable central composite design (RCCD) for optimization on the influence of catalyst’s calcination variables on the CO2 conversion and methanol selectivity is presented. The calcination variables studied include temperature, A (181–518 °C), ramping rate, B (1–30 °C/min), and duration, C (1–7 h). From the RSM-generated model, the optimum calcination condition for this catalyst was 350 °C with 17.5 °C/min ramping rate for a 4 h duration. At the optimum calcination condition, the catalyst exhibited a Brunauer–Emmett–Teller (BET) surface area of 147 m2/g, a pore volume of 0.31 cm3/g, and a pore diameter of 8.1 nm.