bluuebunny/crossref_metadata_2025 huggingface dataset:
A Correlation Study on In Vitro Physiological Activities of Soybean Cultivars, 19 Individual Isoflavone Derivatives, and Genetic Characteristics
Authors: Chu Han-Na , Lee Su-Ji , Wang Xiaohan , Lee Sang-Hoon , Yoon Hye-Myeong , Hwang Yu-Jin , Jung Eun-Suk , Kwon Yongseok , Wee Chi-Do , Jang Kyeong-A , Kim Haeng-Ran
Published: December 2021

The functionality of soybeans is an important factor in the selection and utilization of excellent soybean cultivars, and isoflavones are representative functional substances in soybeans, which exhibit effects on antioxidants, estrogen activity, and cancer, and prevent cardiovascular diseases. This study analyzed ABTS, DPPH, estrogen, ER (ER) alpha, UCP-1, and NO inhibition activities in 48 types of soybean cultivars, as well as the relationship with 19 isolated types of individual isoflavone derivatives. Statistical analysis was conducted to find individual isoflavone derivatives affecting physiological activities, revealing the high correlation of three types of derivatives: genistein 7-O-(6″-O-acetyl)glucoside (6″-O-acetylgenistin), genistein 7-O-(2″-O-apiosyl)glucoside, and glycitein. Based on these results, 15 types of soybean cultivars were selected (one control type, seven yellow types, six black types, and one green type), which have both high physiological activities and a high content of individual isoflavone derivatives. In addition, these high correlations were further verified through a genome-wide association study (GWAS) to determine the association between activities, substances, and genetic characteristics. This study comprehensively describes the relationship between the specific physiological activities of soybean resources, individual isoflavone derivative substances, and SNPs, which will be utilized for in-depth research, such as selection of excellent soybean resources with specific physiological activities.
Preventing Oxidative Stress in the Liver: An Opportunity for GLP-1 and/or PASK
Authors: Hurtado-Carneiro Verónica , Dongil Pilar , Pérez-García Ana , Álvarez Elvira , Sanz Carmen
Published: December 2021

The liver’s high metabolic activity and detoxification functions generate reactive oxygen species, mainly through oxidative phosphorylation in the mitochondria of hepatocytes. In contrast, it also has a potent antioxidant mechanism for counterbalancing the oxidant’s effect and relieving oxidative stress. PAS kinase (PASK) is a serine/threonine kinase containing an N-terminal Per-Arnt-Sim (PAS) domain, able to detect redox state. During fasting/feeding changes, PASK regulates the expression and activation of critical liver proteins involved in carbohydrate and lipid metabolism and mitochondrial biogenesis. Interestingly, the functional inactivation of PASK prevents the development of a high-fat diet (HFD)-induced obesity and diabetes. In addition, PASK deficiency alters the activity of other nutrient sensors, such as the AMP-activated protein kinase (AMPK) and the mammalian target of rapamycin (mTOR). In addition to the expression and subcellular localization of nicotinamide-dependent histone deacetylases (SIRTs). This review focuses on the relationship between oxidative stress, PASK, and other nutrient sensors, updating the limited knowledge on the role of PASK in the antioxidant response. We also comment on glucagon-like peptide 1 (GLP-1) and its collaboration with PASK in preventing the damage associated with hepatic oxidative stress. The current knowledge would suggest that PASK inhibition and/or exendin-4 treatment, especially under fasting conditions, could ameliorate disorders associated with excess oxidative stress.
Hepatoprotective Effect of Bee Bread in Metabolic Dysfunction-Associated Fatty Liver Disease (MAFLD) Rats: Impact on Oxidative Stress and Inflammation
Authors: Zakaria Zaida , Othman Zaidatul Akmal , Suleiman Joseph Bagi , Che Jalil Nur Asyilla , Ghazali Wan Syaheedah Wan , Nna Victor Udo , Mohamed Mahaneem
Published: December 2021

Metabolic dysfunction-associated fatty liver disease (MAFLD) is a pathological accumulation of hepatic lipid closely linked with many metabolic disorders, oxidative stress and inflammation. We aimed to evaluate the hepatoprotective effect of bee bread on oxidative stress and inflammatory parameters in MAFLD rats. Twenty-eight male Sprague-Dawley rats were assigned into four groups (n = 7/group): normal control (NC), high-fat diet (HFD), bee bread (HFD + Bb, HFD + 0.5 g/kg/day bee bread) and orlistat (HFD + Or, HFD + 10 mg/kg/day orlistat) groups. After 12 weeks, the HFD group demonstrated significantly higher body weight gain, serum levels of lipids (TG, TC, LDL), liver enzymes (AST, ALT, ALP) and adiponectin, liver lipids (TG, TC) and insulin resistance (HOMA-IR). Furthermore, the HFD group showed significantly decreased antioxidant enzyme activities (GPx, GST, GR, SOD, CAT) and GSH level, and increased liver oxidative stress (TBARS, NO), translocation of Nrf2 to the nucleus, Keap1 expression and inflammation (TNF-α, NF-κβ, MCP-1) together with histopathological alterations (steatosis, hepatocyte hypertrophy, inflammatory cell infiltration, collagen deposition), which indicated the presence of non-alcoholic steatohepatitis (NASH) and fibrosis. Bee bread significantly attenuated all these changes exerted by HFD feeding. In conclusion, our results suggest that bee bread might have antioxidant, anti-inflammatory, anti-steatotic and anti-fibrotic effects that are beneficial in protecting liver progression towards NASH and fibrosis.
Anti-Amnesic Effects of Epigallocatechin Gallate on Scopolamine-Induced Learning and Memory Dysfunction in Sprague-Dawley Rats
Authors: Kim Min-Jeong , Hwang Eun-Sang , Kim Kwan Joong , Maeng Sungho , Heo Ho Jin , Park Ji-Ho , Kim Dae-Ok
Published: December 2021

Epigallocatechin gallate (EGCG) is a major flavan-3-ol of green tea polyphenols that exhibits various beneficial health effects, including antioxidant, anti-bacterial, and anti-inflammatory properties. This study aimed to evaluate whether EGCG prevents scopolamine-induced learning and memory impairment in in vivo and ex vivo models. Male Sprague-Dawley (SD) rats were pre-treated with EGCG (5 mg/kg/day; intraperitoneal injection (i.p.)) for 10 days. Then, EGCG and scopolamine (1 mg/kg/day; i.p.) were applied 60 and 30 min before the behavioral tests, respectively, for another 9 days. EGCG alleviated the cognitive deficits in the Y-maze, passive avoidance, and Morris water maze tests. EGCG showed improved cholinergic functions by decreasing acetylcholinesterase activity in hippocampi dissected from the brain of the rats after the behavioral tests. EGCG also reduced oxidative stress, partly due to increased superoxide dismutase activity and decreased malondialdehyde level in the hippocampi of the rat brains after the behavioral tests. Furthermore, EGCG attenuated the scopolamine-induced blockade of long-term potentiation in organotypic hippocampal tissue of seven-day-old SD rats. Taken together, these results suggested that EGCG is a potential therapeutic agent for alleviating cognitive dysfunction.
Deformation Characteristic of a Supported Deep Excavation System: A Case Study in Red Sandstone Stratum
Authors: Liu Weizheng , Li Tianxiong , Wan Jiale
Published: December 2021

A complete case record of a deep foundation pit with pile-anchor retaining structure excavated in red sandstone stratum is presented in this study. The horizontal displacement of pile top, the horizontal displacement at various depths, the axial force of anchor cable, and ground settlement during construction are measured. A three-dimensional numerical model is established to analyze the additional stress and deformation induced by the excavation and the accuracy of the FEM model is verified by comparing with field measured results. Both the measured and numerical simulation results show that the deformation of the pile-anchor supported deep excavation is significantly affected by the spatial effect. The results show that the deformation in the middle of the foundation pit is greater than the pit angle and that the deformation of the long side is greater than that of the short side and gradually decreases from the middle to the pit angle. The deformation and stress in the middle of the long side of the foundation pit are the largest, which is the most unfavorable part. With the increase of vertical excavation depth, the spatial effects tend to increase, and the influence scope of spatial effects is about five times the vertical excavation depth in the red sandstone stratum. The ground settlement outside the pit is mainly distributed in a groove shape, and the maximum settlement occurs about 8.5 m away from the pit edge. Finally, parametric studies of reinforcement parameters indicated that 1.5–2.0 times the initial elastic modulus and cohesive force of soil should be used for reinforcement. It is recommended that the ranges for pile diameter, pile spacing, anchor cable prestressing and inclination angle should be selected as 0.8–1.2 m, 1.4–2.0 m, 100–150 kN, and 10°–20°, respectively.
The Resistance Force of the Anterior Cruciate Ligament during Pull Probing Is Related to the Mechanical Property
Authors: Hananouchi Takehito , Suzuki Tomoyuki , Dorthe Erik W. , Du Jiang , D’Lima Darryl D.
Published: December 2021

There are various methods for reconstructing the anterior cruciate ligament (ACL) from other muscles or tendons. Initial tension of the reconstructed ACL is one of the key elements affecting postoperative outcomes. However, tension cannot be measured after graft fixation. The only intraoperative assessment is pull probing, which is performed by pulling joint soft tissues with the arthroscopic probe and can be measured quantitatively. Therefore, its value might be used as an alternative value for the mechanical property of the ACL. Using a probing device one author developed to measure the resistance force of soft tissues quantitatively while probing, we measured the resistance force of dissected ACLs and used tensile testing to investigate the correlation between the resistance force and the mechanical property of the ligaments. According to the results, when a certain amount of tension (strain; 16.6%) was applied, its mechanical properties were moderately correlated (r = 0.56 [p = 0.045]) with the probing force. Therefore, the tension of the reconstructed ACL after fixation under real ACL reconstruction surgery can be derived from the value of the probing device.
How Lineage Tracing Studies Can Unveil Tumor Heterogeneity in Breast Cancer
Authors: Vinuesa-Pitarch Elena , Ortega-Álvarez Daniel , Rodilla Verónica
Published: December 2021

Lineage tracing studies have become a well-suited approach to reveal cellular hierarchies and tumor heterogeneity. Cellular heterogeneity, particularly in breast cancer, is still one of the main concerns regarding tumor progression and resistance to anti-cancer therapies. Here, we review the current knowledge about lineage tracing analyses that have contributed to an improved comprehension of the complexity of mammary tumors, highlighting how targeting different mammary epithelial cells and tracing their progeny can be useful to explore the intra- and inter-heterogeneity observed in breast cancer. In addition, we examine the strategies used to identify the cell of origin in different breast cancer subtypes and summarize how cellular plasticity plays an important role during tumorigenesis. Finally, we evaluate the clinical implications of lineage tracing studies and the challenges remaining to address tumor heterogeneity in breast cancer.
Characterization of the Gut Microbiota in Individuals with Overweight or Obesity during a Real-World Weight Loss Dietary Program: A Focus on the Bacteroides 2 Enterotype
Authors: Alili Rohia , Belda Eugeni , Fabre Odile , Pelloux Véronique , Giordano Nils , Legrand Rémy , Bel Lassen Pierre , Swartz Timothy D. , Zucker Jean-Daniel , Clément Karine
Published: December 2021

Background: Dietary intervention is a cornerstone of weight loss therapies. In obesity, a dysbiotic gut microbiota (GM) is characterized by high levels of Bacteroides lineages and low diversity. We examined the GM composition changes, including the Bacteroides 2 enterotype (Bact2), in a real-world weight loss study in subjects following a high-protein hypocaloric diet with or without a live microorganisms (LMP) supplement. Method: 263 volunteers were part of this real-world weight loss program. The first phase was a high-protein low-carbohydrate calorie restriction diet with or without LMP supplements. Fecal samples were obtained at baseline and after 10% weight loss for 163 subjects. Metagenomic profiling was obtained by shotgun sequencing. Results: At baseline, the Bact2 enterotype was more prevalent in subjects with aggravated obesity and metabolic alterations. After weight loss, diversity increased and Bact2 prevalence decreased in subjects with lower GM diversity at baseline, notably in LMP consumers. Significant increases in Akkermansia muciniphila and Parabacteroides distasonis and significant decreases of Eubacterium rectale, Streptococcus thermophilus and Bifidobacterial lineages were observed after weight loss. Conclusions: Baseline microbiome composition is associated with differential changes in GM diversity and Bact2 enterotype prevalence after weight loss. Examining these signatures could drive future personalized nutrition efforts towards more favorable microbiome compositions.
Peripheral Nerve Stimulation: The Evolution in Pain Medicine
Authors: Abd-Elsayed Alaa , D’Souza Ryan S.
Published: December 2021

Electrical stimulation of peripheral nerves has been utilized for a variety of indications for over five decades [...]
Improved Vascularization and Survival of White Compared to Brown Adipose Tissue Grafts in the Dorsal Skinfold Chamber
Authors: Weinzierl Andrea , Harder Yves , Schmauss Daniel , Ampofo Emmanuel , Menger Michael D. , Laschke Matthias W.
Published: December 2021

Fat grafting is a frequently applied procedure in plastic surgery for volume reconstruction. Moreover, the transplantation of white adipose tissue (WAT) and brown adipose tissue (BAT) increasingly gains interest in preclinical research for the treatment of obesity-related metabolic defects. Therefore, we herein directly compared the vascularization capacity and survival of WAT and BAT grafts. For this purpose, size-matched grafts isolated from the inguinal WAT pad and the interscapular BAT depot of C57BL/6N donor mice were syngeneically transplanted into the dorsal skinfold chamber of recipient animals. The vascularization and survival of the grafts were analyzed by means of intravital fluorescence microscopy, histology, and immunohistochemistry over an observation period of 14 days. WAT grafts showed an identical microvascular architecture and functional microvessel density as native WAT. In contrast, BAT grafts developed an erratic microvasculature with a significantly lower functional microvessel density when compared to native BAT. Accordingly, they also contained a markedly lower number of CD31-positive microvessels, which was associated with a massive loss of perilipin-positive adipocytes. These findings indicate that in contrast to WAT grafts, BAT grafts exhibit an impaired vascularization capacity and survival, which may be due to their higher metabolic demand. Hence, future studies should focus on the establishment of strategies to improve the engraftment of transplanted BAT.
Cancer Studies under Space Conditions: Finding Answers Abroad
Authors: Cortés-Sánchez José Luis , Callant Jonas , Krüger Marcus , Sahana Jayashree , Kraus Armin , Baselet Bjorn , Infanger Manfred , Baatout Sarah , Grimm Daniela
Published: December 2021

In this review article, we discuss the current state of knowledge in cancer research under real and simulated microgravity conditions and point out further research directions in this field. Outer space is an extremely hostile environment for human life, with radiation, microgravity, and vacuum posing significant hazards. Although the risk for cancer in astronauts is not clear, microgravity plays a thought-provoking role in the carcinogenesis of normal and cancer cells, causing such effects as multicellular spheroid formation, cytoskeleton rearrangement, alteration of gene expression and protein synthesis, and apoptosis. Furthermore, deleterious effects of radiation on cells seem to be accentuated under microgravity. Ground-based facilities have been used to study microgravity effects in addition to laborious experiments during parabolic flights or on space stations. Some potential ‘gravisensors’ have already been detected, and further identification of these mechanisms of mechanosensitivity could open up ways for therapeutic influence on cancer growth and apoptosis. These novel findings may help to find new effective cancer treatments and to provide health protection for humans on future long-term spaceflights and exploration of outer space.
Movement Disorders in Oncology: From Clinical Features to Biomarkers
Authors: Marsili Luca , Vogrig Alberto , Colosimo Carlo
Published: December 2021

Background: the study of movement disorders associated with oncological diseases and anticancer treatments highlights the wide range of differential diagnoses that need to be considered. In this context, the role of immune-mediated conditions is increasingly recognized and relevant, as they represent treatable disorders. Methods: we reappraise the phenomenology, pathophysiology, diagnostic testing, and treatment of movement disorders observed in the context of brain tumors, paraneoplastic conditions, and cancer immunotherapy, such as immune-checkpoint inhibitors (ICIs). Results: movement disorders secondary to brain tumors are rare and may manifest with both hyper-/hypokinetic conditions. Paraneoplastic movement disorders are caused by antineuronal antibodies targeting intracellular or neuronal surface antigens, with variable prognosis and response to treatment. ICIs promote antitumor response by the inhibition of the immune checkpoints. They are effective treatments for several malignancies, but they may cause movement disorders through an unchecked immune response. Conclusions: movement disorders due to focal neoplastic brain lesions are rare but should not be missed. Paraneoplastic movement disorders are even rarer, and their clinical-laboratory findings require focused expertise. In addition to their desired effects in cancer treatment, ICIs can induce specific neurological adverse events, sometimes manifesting with movement disorders, which often require a case-by-case, multidisciplinary, approach.
Treatment of Fungal-Infected Diabetic Wounds with Low Temperature Plasma
Authors: Choi Kyu Young , Sultan Md. Tipu , Ajiteru Olatunji , Hong Heesun , Lee Young Jin , Lee Ji Seung , Lee Hanna , Lee Ok Joo , Kim Soon Hee , Lee Joong Seob , Park Sung-Jin , Eden James Gary , Park Chan Hum
Published: December 2021

Diabetes mellitus renders patients susceptible to chronic wounds and various infections. Regarding the latter, fungal infections are of particular concern since, although they are the source of significant morbidity and mortality in immunocompromised patients, they are generally resistant to conventional treatment and a definite treatment strategy has not yet been established. Herein, we report the treatment of skin wounds in a diabetic rat model, infected by Candida albicans, with low temperature helium plasma generated in a hand-held atmospheric jet device. A fungal infection was induced on two dorsal skin wounds of the diabetic rats, and one wound was treated with the plasma jet whereas the other served as a control. Histological analysis revealed accelerated skin wound healing and decreased evidence of fungal infection in the plasma-treated group, as compared to the control group. Regeneration of the epidermis and dermis, collagen deposition, and neovascularization were all observed as a result of plasma treatment, but without wound contraction, scar formation or any evidence of thermal damage to the tissue. These findings demonstrate that the He plasma jet is remarkably effective in diabetic skin wounds infected by Candida albicans, thereby providing a promising medical treatment option for diabetes mellitus patients with skin wound and fungal infections.
Investigation of the Morphology and Electrical Properties of Graphene Used in the Development of Biosensors for Detection of Influenza Viruses
Authors: Shmidt Natalia M. , Usikov Alexander S. , Shabunina Evgeniia I. , Nashchekin Alexey V. , Gushchina Ekaterina V. , Eliseev Ilya A. , Petrov Vasily N. , Puzyk Mikhail V. , Avdeev Oleg V. , Klotchenko Sergey A. , Lebedev Sergey P. , Tanklevskaya Elena M. , Makarov Yuri N. , Lebedev Alexander A. , Vasin Andrey V.
Published: December 2021

In this study, we discuss the mechanisms behind changes in the conductivity, low-frequency noise, and surface morphology of biosensor chips based on graphene films on SiC substrates during the main stages of the creation of biosensors for detecting influenza viruses. The formation of phenylamine groups and a change in graphene nano-arrangement during functionalization causes an increase in defectiveness and conductivity. Functionalization leads to the formation of large hexagonal honeycomb-like defects up to 500 nm, the concentration of which is affected by the number of bilayer or multilayer inclusions in graphene. The chips fabricated allowed us to detect the influenza viruses in a concentration range of 10−16 g/mL to 10−10 g/mL in PBS (phosphate buffered saline). Atomic force microscopy (AFM) and scanning electron microscopy (SEM) revealed that these defects are responsible for the inhomogeneous aggregation of antibodies and influenza viruses over the functionalized graphene surface. Non-uniform aggregation is responsible for a weak non-linear logarithmic dependence of the biosensor response versus the virus concentration in PBS. This feature of graphene nano-arrangement affects the reliability of detection of extremely low virus concentrations at the early stages of disease.
Semantic Verbal Fluency in Youth with Down Syndrome: Analysis of Conventional and Contextual Cluster Formation
Authors: Schworer Emily K. , Belizaire Shequanna , Hoffman Emily K. , Esbensen Anna J.
Published: December 2021

Expressive language delays and executive functioning challenges are common in youth with Down syndrome (DS). Verbal fluency is one method to investigate these constructs. We examined semantic verbal fluency responses to determine patterns in response generation and the psychometric properties of coded cluster formations. Participants were 97 children and adolescents with DS ranging in age from 6 to 19 years old. The semantic verbal fluency task was administered at two time points, two weeks apart. Heterogeneity in performance was observed for responses when coded either with conventional or contextual classifications. Overall, the number of switches in conventional classifications was greater than contextual classifications. This implies that participants did not use traditional (conventional) categories to organize their semantic verbal fluency responses, but may have been using contextual strategies. However, the number of switches and cluster size variables had poor to moderate test–retest reliability, which indicated that participants did not stay consistent with their performance over the two-week testing interval, regardless of the strategies used. Therefore, conventional and contextual clusters and switches as a measure of executive control may not be appropriate for all individuals with DS and additional attention is warranted to determine the utility of response coding in this population.
The Organ of Vision and the Stomatognathic System—Review of Association Studies and Evidence-Based Discussion
Authors: Zieliński Grzegorz , Filipiak Zuzanna , Ginszt Michał , Matysik-Woźniak Anna , Rejdak Robert , Gawda Piotr
Published: December 2021

The stomatognathic system is a functional complex of tissues and organs located within the oral and craniofacial cavities. The craniofacial anatomical factors and the biomechanics of the temporomandibular joints affect many systems throughout the body, including the organ of vision. However, few scientific reports have shown a relationship between the organ of vision and the stomatognathic system. The purpose of this review is to provide an overview of connections along neural, muscle-fascial, and biochemical pathways between the organ of vision and the stomatognathic system. Based on the literature presented in this review, the connections between the organ of vision and the stomatognathic system seem undeniable. Understanding the anatomical, physiological, and biochemical interrelationships may allow to explain the interactions between the mentioned systems. According to the current knowledge, it is not possible to indicate the main linking pathway; presumably, it may be a combination of several presented pathways. The awareness of this relationship among dentists, ophthalmologists, physiotherapists, and optometrists should increase for the better diagnosis and treatment of patients.
Preventing and Overcoming Resistance to PARP Inhibitors: A Focus on the Clinical Landscape
Authors: Prados-Carvajal Rosario , Irving Elsa , Lukashchuk Natalia , Forment Josep V.
Published: December 2021

Poly(ADP-ribose) polymerase (PARP) inhibitors (PARPi) are now a first-line maintenance treatment in ovarian cancer and have been approved in other cancer types, including breast, pancreatic and prostate. Despite their efficacy, and as is the case for other targeted therapies, resistance to PARPi has been reported clinically and is generating a growing patient population of unmet clinical need. Here, we discuss the mechanisms of resistance that have been described in pre-clinical models and focus on those that have been already identified in the clinic, highlighting the key challenges to fully characterise the clinical landscape of PARPi resistance and proposing ways of preventing and overcoming it.
Validation of Breast Cancer Risk Models by Race/Ethnicity, Family History and Molecular Subtypes
Authors: McCarthy Anne Marie , Liu Yi , Ehsan Sarah , Guan Zoe , Liang Jane , Huang Theodore , Hughes Kevin , Semine Alan , Kontos Despina , Conant Emily , Lehman Constance , Armstrong Katrina , Braun Danielle , Parmigiani Giovanni , Chen Jinbo
Published: December 2021

(1) Background: The purpose of this study is to compare the performance of four breast cancer risk prediction models by race, molecular subtype, family history of breast cancer, age, and BMI. (2) Methods: Using a cohort of women aged 40–84 without prior history of breast cancer who underwent screening mammography from 2006 to 2015, we generated breast cancer risk estimates using the Breast Cancer Risk Assessment tool (BCRAT), BRCAPRO, Breast Cancer Surveillance Consortium (BCSC) and combined BRCAPRO+BCRAT models. Model calibration and discrimination were compared using observed-to-expected ratios (O/E) and the area under the receiver operator curve (AUC) among patients with at least five years of follow-up. (3) Results: We observed comparable discrimination and calibration across models. There was no significant difference in model performance between Black and White women. Model discrimination was poorer for HER2+ and triple-negative subtypes compared with ER/PR+HER2−. The BRCAPRO+BCRAT model displayed improved calibration and discrimination compared to BRCAPRO among women with a family history of breast cancer. Across models, discriminatory accuracy was greater among obese than non-obese women. When defining high risk as a 5-year risk of 1.67% or greater, models demonstrated discordance in 2.9% to 19.7% of patients. (4) Conclusions: Our results can inform the implementation of risk assessment and risk-based screening among women undergoing screening mammography.
Cell Death in Hepatocellular Carcinoma: Pathogenesis and Therapeutic Opportunities
Authors: García-Pras Ester , Fernández-Iglesias Anabel , Gracia-Sancho Jordi , Pérez-del-Pulgar Sofía
Published: December 2021

Hepatocellular carcinoma (HCC) is the most prevalent primary liver cancer and the third leading cause of cancer death worldwide. Closely associated with liver inflammation and fibrosis, hepatocyte cell death is a common trigger for acute and chronic liver disease arising from different etiologies, including viral hepatitis, alcohol abuse, and fatty liver. In this review, we discuss the contribution of different types of cell death, including apoptosis, necroptosis, pyroptosis, or autophagy, to the progression of liver disease and the development of HCC. Interestingly, inflammasomes have recently emerged as pivotal innate sensors with a highly pathogenic role in various liver diseases. In this regard, an increased inflammatory response would act as a key element promoting a pro-oncogenic microenvironment that may result not only in tumor growth, but also in the formation of a premetastatic niche. Importantly, nonparenchymal hepatic cells, such as liver sinusoidal endothelial cells, hepatic stellate cells, and hepatic macrophages, play an important role in establishing the tumor microenvironment, stimulating tumorigenesis by paracrine communication through cytokines and/or angiocrine factors. Finally, we update the potential therapeutic options to inhibit tumorigenesis, and we propose different mechanisms to consider in the tumor microenvironment field for HCC resolution.
Targeting the Intrinsic Apoptosis Pathway: A Window of Opportunity for Prostate Cancer
Authors: Westaby Daniel , Jimenez-Vacas Juan M. , Padilha Ana , Varkaris Andreas , Balk Steven P. , de Bono Johann S. , Sharp Adam
Published: December 2021

Despite major improvements in the management of advanced prostate cancer over the last 20 years, the disease remains invariably fatal, and new effective therapies are required. The development of novel hormonal agents and taxane chemotherapy has improved outcomes, although primary and acquired resistance remains problematic. Inducing cancer cell death via apoptosis has long been an attractive goal in the treatment of cancer. Apoptosis, a form of regulated cell death, is a highly controlled process, split into two main pathways (intrinsic and extrinsic), and is stimulated by a multitude of factors, including cellular and genotoxic stress. Numerous therapeutic strategies targeting the intrinsic apoptosis pathway are in clinical development, and BH3 mimetics have shown promising efficacy for hematological malignancies. Utilizing these agents for solid malignancies has proved more challenging, though efforts are ongoing. Molecular characterization and the development of predictive biomarkers is likely to be critical for patient selection, by identifying tumors with a vulnerability in the intrinsic apoptosis pathway. This review provides an up-to-date overview of cell death and apoptosis, specifically focusing on the intrinsic pathway. It summarizes the latest approaches for targeting the intrinsic apoptosis pathway with BH3 mimetics and discusses how these strategies may be leveraged to treat prostate cancer.
Late Cardiological Sequelae and Long-Term Monitoring in Classical Hodgkin Lymphoma and Diffuse Large B-Cell Lymphoma Survivors: A Systematic Review by the Fondazione Italiana Linfomi
Authors: Oliva Stefano , Puzzovivo Agata , Gerardi Chiara , Allocati Eleonora , De Sanctis Vitaliana , Minoia Carla , Skrypets Tetiana , Guarini Attilio , Gini Guido
Published: December 2021

Cardiotoxicity represents the most frequent cause with higher morbidity and mortality among long-term sequelae affecting classical Hodgkin lymphoma (cHL) and diffuse large B-cell lymphoma (DLBCL) patients. The multidisciplinary team of Fondazione Italiana Linfomi (FIL) researchers, with the methodological guide of Istituto di Ricerche Farmacologiche “Mario Negri”, conducted a systematic review of the literature (PubMed, EMBASE, Cochrane database) according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, in order to analyze the following aspects of cHL and DLBCL survivorship: (i) incidence of cardiovascular disease (CVD); (ii) risk of long-term CVD with the use of less cardiotoxic therapies (reduced-field radiotherapy and liposomal doxorubicin); and (iii) preferable cardiovascular monitoring for left ventricular (LV) dysfunction, coronary heart disease (CHD) and valvular disease (VHD). After the screening of 659 abstracts and related 113 full-text papers, 23 publications were eligible for data extraction and included in the final sample. There was an increased risk for CVD in cHL survivors of 3.6 for myocardial infarction and 4.9 for congestive heart failure (CHF) in comparison to the general population; the risk increased over the years of follow-up. In addition, DLBCL patients presented a 29% increased risk for CHF. New radiotherapy techniques suggested reduced risk of late CVD, but only dosimetric studies were available. The optimal monitoring of LV function by 2D-STE echocardiography should be structured according to individual CV risk, mainly considering as risk factors a cumulative doxorubicine dose >250 mg per square meter (m2) and mediastinal radiotherapy >30 Gy, age at treatment <25 years and age at evaluation >60 years, evaluating LV ejection fraction, global longitudinal strain, and global circumferential strain. The evaluation for asymptomatic CHD should be offered starting from the 10th year after mediastinal RT, considering ECG, stress echo, or coronary artery calcium (CAC) score. Given the suggested increased risks of cardiovascular outcomes in lymphoma survivors compared to the general population, tailored screening and prevention programs may be warranted to offset the future burden of disease.
The Omentum in Obesity-Associated Cancer: A Hindrance to Effective Natural Killer Cell Migration towards Tumour Which Can Be Overcome by CX3CR1 Antagonism
Authors: Mylod Eimear , O’Connell Fiona , Donlon Noel E. , Butler Christine , Reynolds John V. , Lysaght Joanne , Conroy Melissa J.
Published: December 2021

Oesophagogastric adenocarcinomas (OAC) are obesity-associated malignancies, underpinned by severe immune dysregulation. We have previously shown that natural killer (NK) cells preferentially migrate to OAC omentum, where they undergo phenotypic and functional alterations and apoptosis. Furthermore, we have identified the CX3CR1:fractalkine (CX3CL1) pathway as pivotal in their recruitment to omentum. Here, we elucidate whether exposure to the soluble microenvironment of OAC omentum, and in particular fractalkine and IL-15 affects NK cell homing capacity towards oesophageal tumour. Our data uncover diminished NK cell migration towards OAC tumour tissue conditioned media (TCM) following exposure to omental adipose tissue conditioned media (ACM) and reveal that this migration can be rescued with CX3CR1 antagonist E6130. Furthermore, we show that fractalkine has opposing effects on NK cell migration towards TCM, when used alone or in combination with IL-15 and uncover its inhibitory effects on IL-15-mediated stimulation of death receptor ligand expression. Interestingly, treatment with fractalkine and/or IL-15 do not significantly affect NK cell adhesion to MAdCAM-1, despite changes they elicit to the expression of integrin α4β7. This study provides further evidence that CX3CR1 antagonism has therapeutic utility in rescuing NK cells from the deleterious effects of the omentum and fractalkine in OAC, thus limiting their dysfunction.
Dopamine D4 Receptor Is a Regulator of Morphine-Induced Plasticity in the Rat Dorsal Striatum
Authors: Rivera Alicia , Suárez-Boomgaard Diana , Miguelez Cristina , Valderrama-Carvajal Alejandra , Baufreton Jérôme , Shumilov Kirill , Taupignon Anne , Gago Belén , Real M. Ángeles
Published: December 2021

Long-term exposition to morphine elicits structural and synaptic plasticity in reward-related regions of the brain, playing a critical role in addiction. However, morphine-induced neuroadaptations in the dorsal striatum have been poorly studied despite its key function in drug-related habit learning. Here, we show that prolonged treatment with morphine triggered the retraction of the dendritic arbor and the loss of dendritic spines in the dorsal striatal projection neurons (MSNs). In an attempt to extend previous findings, we also explored whether the dopamine D4 receptor (D4R) could modulate striatal morphine-induced plasticity. The combined treatment of morphine with the D4R agonist PD168,077 produced an expansion of the MSNs dendritic arbors and restored dendritic spine density. At the electrophysiological level, PD168,077 in combination with morphine altered the electrical properties of the MSNs and decreased their excitability. Finally, results from the sustantia nigra showed that PD168,077 counteracted morphine-induced upregulation of μ opioid receptors (MOR) in striatonigral projections and downregulation of G protein-gated inward rectifier K+ channels (GIRK1 and GIRK2) in dopaminergic cells. The present results highlight the key function of D4R modulating morphine-induced plasticity in the dorsal striatum. Thus, D4R could represent a valuable pharmacological target for the safety use of morphine in pain management.
A Journey towards Understanding the Molecular Pathology and Developing Therapies for Lysosomal Storage Disorders
Authors: Tikkanen Ritva
Published: December 2021

Lysosomal storage disorders (LSDs) are rare, monogenic diseases characterized by aberrant lysosomes with storage material [...]
Analyses of Lysin-motif Receptor-like Kinase (LysM-RLK) Gene Family in Allotetraploid Brassica napus L. and Its Progenitor Species: An In Silico Study
Authors: Abedi Amin , Hajiahmadi Zahra , Kordrostami Mojtaba , Esmaeel Qassim , Jacquard Cédric
Published: December 2021

The LysM receptor-like kinases (LysM-RLKs) play a crucial role in plant symbiosis and response to environmental stresses. Brassica napus, B. rapa, and B. oleracea are utilized as valuable vegetables. Different biotic and abiotic stressors affect these crops, resulting in yield losses. Therefore, genome-wide analysis of the LysM-RLK gene family was conducted. From the genome of the examined species, 33 LysM-RLK have been found. The conserved domains of Brassica LysM-RLKs were divided into three groups: LYK, LYP, and LysMn. In the BrassicaLysM-RLK gene family, only segmental duplication has occurred. The Ka/Ks ratio for the duplicated pair of genes was less than one indicating that the genes’ function had not changed over time. The BrassicaLysM-RLKs contain 70 cis-elements, indicating that they are involved in stress response. 39 miRNA molecules were responsible for the post-transcriptional regulation of 12 Brassica LysM-RLKs. A total of 22 SSR loci were discovered in 16 Brassica LysM-RLKs. According to RNA-seq data, the highest expression in response to biotic stresses was related to BnLYP6. According to the docking simulations, several residues in the active sites of BnLYP6 are in direct contact with the docked chitin and could be useful in future studies to develop pathogen-resistant B. napus. This research reveals comprehensive information that could lead to the identification of potential genes for Brassica species genetic manipulation.
Development of a Mechanistic Method to Obtain Load Position Strain in Instrumented Pavement
Authors: Hu Guiling , Han Wenyang , Wei Jincheng , Wang Deqing , Zhang Xiaomeng , Hu Wenjun , Chen Wei
Published: December 2021

To study the in-situ response and performance of asphalt pavement, instrumenting pavement with a variety of sensors has become one of the most important tools in the field or accelerated load facilities. In the dynamic response collection process, engineers are more concerned with the load position strain of the pavement structure due to wheel wander. This paper proposes a method to obtain the load position and the strain at the load position when there is no lateral-axis positioning system based on multilayer elastic theory. The test section was paved in the field with installed strain sensors to verify and apply the proposed method. The verification results showed that both the calculated load position and load position strain matched the measured values with an absolute difference range of 5–60 mm, 0.5–2.5 με, respectively. The application results showed that the strain at the load position calculated by the proposed method had a good correlation with the temperature, as expected.
Cryptomphalus aspersa Eggs Extract Potentiates Human Epidermal Stem Cell Regeneration and Amplification
Authors: San Juan Lucía , de Pedro Isabel , Rodríguez-Luna Azahara , Villalba María , Guerrero Antonio , González Salvador , Gandarillas Alberto
Published: December 2021

Modern life and extended life expectancy have prompted the search for natural compounds alleviating skin aging. Evidence supports the beneficial effects on skin integrity and health from the topical administration of preparations of the mollusc Cryptomphalus aspersa eggs extract (IFC-CAF®) and suggests these effects are partly derived from an impact on skin renewal and repair mechanisms. The objective was to dissect in vitro the specific impact of IFC-CAF® on different parameters related to the regenerative potential, differentiation phenotype and exhaustion of skin stem cells. A prominent impact of IFC-CAF® was the induction of stratification and differentiated phenotypes from skin stem cells. IFC-CAF® slowed down the cell cycle at the keratinocyte DNA repair phase and, decelerated proliferation. However, it preserved the proliferative potential of the stem cells. IFC-CAF® reduced the DNA damage marker, γH2AX, and induced the expression of the transcription factor p53. These features correlated with significant protection in telomere shortening upon replicative exhaustion. Thus, IFC-CAF® helps maintain orderly cell cycling and differentiation, thus potentiating DNA repair and integrity. Our observations support the regenerative and repair capacity of IFC-CAF® on skin, through the improved mobilization and ordered differentiation of keratinocyte precursors and the enhancement of genome surveillance and repair mechanisms that counteract aging.
Epibiotic Communities of Common Crab Species in the Coastal Barents Sea: Biodiversity and Infestation Patterns
Authors: Dvoretsky Alexander G. , Dvoretsky Vladimir G.
Published: December 2021

Crabs are important ecosystem engineers in marine habitats worldwide. Based on long-term data, we analyzed the species composition and infestation indices of epibionts and symbionts colonizing the great spider crab, Hyas araneus, and two lithodid crabs—the northern stone crab, Lithodes maja, and the red king crab, Paralithodes camtschaticus—in the coastal zone of the Barents Sea. The epibiotic communities found on great spider crabs were closer to northern stone crabs (33%) compared to red king crabs (25%). The prevalence of mobile symbionts (amphipods, Ischyrocerus, and polychaetes, Harmothoe) and common epibionts, such as barnacles and hydrozoans, was low on great spider crabs and high on the body and in the gills of lithodid crabs. Epiphytes were abundant on great spider crabs but not present on both species of lithodid crabs. Egg symbionts found on H. araneus and P. camtschaticus do not affect their local populations. Differences in the fouling communities found on the three crab species are associated with host size range, surface properties of their carapaces, and behavior patterns.
Datasets for the Determination of Evaporative Flux from Distilled Water and Saturated Brine Using Bench-Scale Atmospheric Simulators
Authors: Suchan Jared , Azam Shahid
Published: December 2021

Evaporation from fresh water and saline water is critical for the estimation of water budget in the Canadian Prairies. Predictive models using empirical field-based data are subject to significant errors and uncertainty. Therefore, highly controlled test conditions and accurately measured experimental data are required to understand the relationship between atmospheric variables at water surfaces. This paper provides a comprehensive dataset generated for the determination of evaporative flux from distilled water and saturated brine using the bench-scale atmospheric simulator (BAS) and the subsequently improved design (BAS2). Analyses of the weather scenarios from atmospheric parameters and evaporative flux from the experimental data are provided.
The Relationship between Acute and Chronic Pancreatitis with Pancreatic Adenocarcinoma: Review
Authors: Alhobayb Tamara , Peravali Rahul , Ashkar Motaz
Published: December 2021

Pancreatic ductal adenocarcinoma (PDAC) is a lethal disease with poor prognosis, leading to significant cancer-related mortality and an overall five-year survival rate of about nine percent. Acute and chronic pancreatitis have been associated with PDAC through common risk factors based on multiple epidemiological studies. Acute pancreatitis (AP) might be one of the earliest manifestations of PDAC, but evolving chronic pancreatitis (CP) following recurrent bouts of AP has been proposed as a risk factor for cancer development in the setting of persistent inflammation and ongoing exposure to carcinogens. This review aims to highlight the evidence supporting the relationship between acute and chronic pancreatitis with PDAC.
An Automated Behaviour-Based Clustering of IoT Botnets
Authors: Trajanovski Tolijan , Zhang Ning
Published: December 2021

The leaked IoT botnet source-codes have facilitated the proliferation of different IoT botnet variants, some of which are equipped with new capabilities and may be difficult to detect. Despite the availability of solutions for automated analysis of IoT botnet samples, the identification of new variants is still very challenging because the analysis results must be manually interpreted by malware analysts. To overcome this challenge, we propose an approach for automated behaviour-based clustering of IoT botnet samples, aimed to enable automatic identification of IoT botnet variants equipped with new capabilities. In the proposed approach, the behaviour of the IoT botnet samples is captured using a sandbox and represented as behaviour profiles describing the actions performed by the samples. The behaviour profiles are vectorised using TF-IDF and clustered using the DBSCAN algorithm. The proposed approach was evaluated using a collection of samples captured from IoT botnets propagating on the Internet. The evaluation shows that the proposed approach enables accurate automatic identification of IoT botnet variants equipped with new capabilities, which will help security researchers to investigate the new capabilities, and to apply the investigation findings for improving the solutions for detecting and preventing IoT botnet infections.
Coffee By-Products as Sustainable Novel Foods: Report of the 2nd International Electronic Conference on Foods—“Future Foods and Food Technologies for a Sustainable World”
Authors: Lachenmeier Dirk W. , Schwarz Steffen , Rieke-Zapp Jörg , Cantergiani Ennio , Rawel Harshadrai , Martín-Cabrejas María Angeles , Martuscelli Maria , Gottstein Vera , Angeloni Simone
Published: December 2021

The coffee plant Coffea spp. offers much more than the well-known drink made from the roasted coffee bean. During its cultivation and production, a wide variety of by-products are accrued, most of which are currently unused, thermally recycled, or used as fertilizer or animal feed. Modern, ecologically oriented society attaches great importance to sustainability and waste reduction, so it makes sense to not dispose of the by-products of coffee production but to bring them into the value chain, most prominently as foods for human nutrition. There is certainly huge potential for all of these products, especially on markets not currently accessible due to restrictions, such as the novel food regulation in the European Union. The by-products could help mitigate the socioeconomic burden of coffee farmers caused by globally low coffee prices and increasing challenges due to climate change. The purpose of the conference session summarized in this article was to bring together international experts on coffee by-products and share the current scientific knowledge on all plant parts, including leaf, cherry, parchment and silverskin, covering aspects from food chemistry and technology, nutrition, but also food safety and toxicology. The topic raised a huge interest from the audience and this article also contains a Q&A section with more than 20 answered questions.