bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of Animal Fat Replacement by Emulsified Melon and Pumpkin Seed Oils in Deer Burgers
Authors: Martínez Elena , Pardo José E. , Rabadán Adrián , Álvarez-Ortí Manuel
Published: March 2023

Meat products such as burgers contain large amounts of saturated fat and are considered unhealthy foods by a society that is increasingly aware of the impact of food on their health, as there is a widespread idea that the consumption of large amounts of saturated fats is related to cardiovascular diseases, some types of cancer and obesity. The main goal of this study was to reformulate deer burgers by replacing the saturated fat from its composition with emulsions of oil extracted from melon and pumpkin seeds. Three emulsions were made with these oils (guar gum and inulin, sodium alginate and maltodextrin) to obtain a solid texture. Then, burgers were elaborated, using the vegetable oil emulsions to replace partially (50%) or totally (100%) the animal fat usually used in their elaboration. Physical parameters such as color and texture, consumer evaluation, proximate analysis and the fatty acid composition obtained by gas chromatography were analyzed. The burgers made with emulsified oils showed a higher weight loss, but with a minor loss of caliber and hardness (p < 0.05). From the sensory point of view, the reformulated burgers were positively valued by consumer judges when external aspect, odor, flavor and texture were evaluated. Furthermore, the addition of oil emulsions results in a lower fat content and in an increment of the proportion of unsaturated fatty acids, especially linoleic acid (p < 0.05). The inclusion of emulsified melon and pumpkin oil in deer burgers leads to an increase in the content of polyunsaturated fatty acids in burgers that, although they showed small differences in texture attributes (especially hardness and cohesiveness), were well valued by consumer judges in all sensory attributes evaluated.
Advances in the Theory and Applications of Contests and Tournaments: Introduction to the Special Issue
Authors: Tsoulouhas Theofanis
Published: March 2023

The theory of relative performance evaluation has come a long way since its inception, so much so that it is now a major research branch in economic theory [...]
Using Next-Generation Sequencing to Disentangle the Diet and Incidence of Intestinal Parasites of Falkland Flightless Steamer Duck Tachyeres brachypterus and Patagonian Crested Duck Lophonetta specularioides Sharing a South Atlantic Island
Authors: Masello Juan F. , Schumm Yvonne R. , Griep Sven , Quillfeldt Petra
Published: March 2023

Species overlapping in habitat use can cohabit depending on how they exploit resources. To understand segregation in resource use, an exhaustive knowledge of the diet is required. We aimed to disentangle the diet composition of the Falkland Flightless Steamer Duck Tachyeres brachypterus and the Patagonian Crested Duck Lophonetta specularioides sharing a coastal environment. Using DNA extracted from scats and Illumina sequencing, we generated a list of molecular operational taxonomic units. Both ducks consumed a variety of invertebrates, frequently overlapping in the taxa consumed. However, only the Falkland Flightless Steamer Ducks consumed fish, which might be indicative of dietary specialization and inter-specific segregation in the restricted space that these birds share. Moreover, the female and male Falkland Flightless Steamer Ducks consumed different fish prey, with almost one-third of the fish taxa being consumed by females only and another similar number consumed by males only. This result might suggest a case of intra-specific competition, triggering sexual segregation. Additionally, we detected parasitic Platyelminthes (Cestoda and Trematoda), with different frequencies of occurrence, probably related to the different diet compositions of the ducks. This study provides the necessary baseline for future investigations of the ecological segregation of these ducks.
SCN9A rs6746030 Polymorphism and Pain Perception in Combat Athletes and Non-Athletes
Authors: Leźnicka Katarzyna , Pawlak Maciej , Sawczuk Marek , Gasiorowska Agata , Leońska-Duniec Agata
Published: March 2023

One of the genes associated with pain perception is SCN9A, which encodes an α-subunit of the voltage gated sodium channel, NaV1.7, a crucial player in peripheral pain sensation. It has been suggested that a common missense polymorphism within SCN9A (rs6746030; G>A; R1150W) may affect nociception in the general population, but its effects of pain perception in athletes remain unknown. Therefore, the aim of the study was to investigate the association between a polymorphism within SCN9A (rs6746030) and pain perception (pain threshold and pain tolerance) in the group of combat athletes (n = 214) and students (n = 92) who did not participate in sports at a professional level. Genotyping was carried out using TaqMan Real-Time PCR method. No significant differences were found between the SCN9A genotype distributions with respect to the pain threshold. However, the probability of having a high pain threshold was higher in the combat sports group than in the control group. The probability of having a decreased pain tolerance was higher in the carriers of the GA and AA genotype than in the homozygotes of the GG genotype. Moreover, the possibility of having a high pain threshold was higher in the combat athlete group than in the control group. The results of our study suggest that the SCN9A rs6746030 polymorphism may affect pain perception. However, the additional effect of the experimental group may suggest that pain tolerance is significantly modulated by other factors, such as the systematic exposure of the athletes’ bodies to short-term high-intensity stimuli during training sessions.
FERMT1 Is a Prognostic Marker Involved in Immune Infiltration of Pancreatic Adenocarcinoma Correlating with m6A Modification and Necroptosis
Authors: Wu Qian , Li Jin , Wang Pei , Peng Qihang , Kang Zhongcui , Deng Yiting , Li Jiayi , Yan Dehong , Ge Feng , Chen Ying
Published: March 2023

As an important member of the kindlin family, fermitin family member 1 (FERMT1) can interact with integrin and its aberrant expression involves multiple tumors. However, there are few systematic studies on FERMT1 in pancreatic carcinoma (PAAD). We used several public databases to analyze the expression level and clinicopathological characteristics of FERMT1 in PAAD. Meanwhile, the correlation between FERMT1 expression and diagnostic and prognostic value, methylation, potential biological function, immune infiltration, and sensitivity to chemotherapy drugs in PAAD patients were investigated. FERMT1 was significantly up-regulated in PAAD and correlated with T stage, and histologic grade. High FERMT1 expression was closely connected with poor prognosis and can be used to diagnose PAAD. Moreover, the methylation of six CpG sites of FERMT1 was linked to prognosis, and FERMT1 expression was significantly related to N6-methyladenosine (m6A) modification. Functional enrichment analysis revealed that FERMT1 co-expression genes participated in diverse biological functions including necroptosis. In addition, the expression of FERMT1 was associated with immune cell infiltration and the expression of immune checkpoint molecules. Finally, FERMT1 overexpression may be sensitive to chemotherapy drugs such as Palbociclib, AM-5992 and TAE-226. FERMT1 can serve as a diagnostic and prognostic marker of PAAD, which is connected with immune cell infiltration and the modulation of m6A and necroptosis.
Special Issue “Parkinson’s Disease: Genetics and Pathogenesis”
Authors: Lesage Suzanne , Trinh Joanne
Published: March 2023

Parkinson’s disease (PD) is a common and incurable neurodegenerative disease, affecting 1% of the population over the age of 65 [...]
Influence of Climatic Trends and Cycles on Varve Deposition in Crawford Lake, Ontario, Canada
Authors: Lafond Krysten M. , Walsh Carling R. , Patterson R. Timothy , McCarthy Francine M. G. , Llew-Williams Brendan M. , Hamilton Paul B. , Nasser Nawaf A. , Cumming Brian
Published: March 2023

Varves accumulating below the chemocline of meromictic Crawford Lake, Milton, Ontario, Canada, consist of dark-colored organic matter laminations that are primarily deposited during the fall plankton die-off, alternating with light-colored laminations comprising calcite crystals that are precipitated during a relatively narrow water temperature and pH-controlled depositional window in the summer. A novel high-resolution imaging protocol was used to photograph the varve record in the 87 cm-long freeze core CRA19-2FT-B2, collected from the deepest part (~23 m) of the lake in February 2019. High-resolution images were used to: (1) characterize varve couplets deposited between AD 1870 and 2000 (chronology verified through 137Cs/210Pb analysis of freeze core CRA22-1FRA-3, and consistent with the historic record of nuclear fallout and other proxies of the Great Acceleration); (2) document distinctive varves that permit a correlation between cores throughout the deep basin of Crawford Lake; (3) measure the thickness of individual dark and light- colored laminations, which were found to vary between 0.04 mm and 3.76 mm; and (4) carry out wavelet and spectral time series analyses based on varve thickness data that can be correlated to climatic trends and cycles. Time series analyses identified cycles with statistically significant periodicities that were attributed to the Quasi-biennial Oscillation (2.3 years), El Niño Southern Oscillation (2–7 years), the 11-year Schwabe Sunspot cycle and a possible Pacific Decadal Oscillation (50–70 years). This research not only provides baseline chronostratigraphic data that allow the correlation between freeze cores subsampled for various proxies, but also documents the dynamics of the climate drivers that influence the deposition of both organic matter and inorganically precipitated calcite. Crawford Lake is currently a candidate site under consideration for the Global boundary Stratotype Section and Point (GSSP) to define the Anthropocene series/epoch.
Alzheimer’s Disease and Alzheimer’s Disease-Related Dementias in African Americans: Focus on Caregivers
Authors: Kopel Jonathan , Sehar Ujala , Choudhury Moumita , Reddy P. Hemachandra
Published: March 2023

Alzheimer’s disease (AD) and Alzheimer’s Disease-Related Dementias (ADRD) are chronic illnesses that are highly prevalent in African Americans (AA). AD and ADRD are caused by multiple factors, such as genetic mutations, modifiable and non-modifiable risk factors, and lifestyle. Histopathological, morphological, and cellular studies revealed how multiple cellular changes are implicated in AD and ADRD, including synaptic damage, inflammatory responses, hormonal imbalance, mitochondrial abnormalities, and neuronal loss, in addition to the accumulation of amyloid beta and phosphorylated tau in the brain. The contributions of race, ethnicity, location and socioeconomic status all have a significant impact on the care and support services available to dementia patients. Furthermore, disparities in health care are entangled with social, economic, and environmental variables that perpetuate disadvantages among different groups, particularly African Americans. As such, it remains important to understand how various racial and ethnic groups perceive, access, and experience health care. Considering that the mounting data shows AA may be more susceptible to AD than white people, the demographic transition creates significant hurdles in providing adequate care from family caregivers. Furthermore, there is growing recognition that AD and ADRD pose a significant stress on AA caregivers compared to white people. In this review, we examine the current literature on racial disparities in AD and ADRD, particularly concerning AA caregivers.
Associations between Autonomic and Endocrine Reactivity to Stress in Adolescence: Related to the Development of Anxiety?
Authors: Stam Jacqueline V. , Kallen Victor L. , Westenberg P. Michiel
Published: March 2023

Internalizing disorders in adolescence have been associated with disturbances in autonomic and endocrine functioning. Because the prefrontal cortex and the limbic system play a central role in regulating both the autonomic and the endocrine systems, their joint functioning is hypothesized to provide information about the potential development of internalizing symptoms throughout adolescence, notably in the preclinical stage. This hypothesis was tested in a sample of 198 adolescents from the general population. Heart rate variability (HRV) and skin conductance levels (SCLs) were measured before, during, and after a public speaking task. These autonomic parameters were associated with cortisol response to the task in the complete sample as well as in low- and high-anxiety adolescents separately. Self-reported social anxiety, low HRV, and high SCL recovery values were predictive of cortisol response. Importantly, in low-anxiety adolescents, only HRV during the task predicted the cortisol response, whereas, in their highly anxious peers, both HRV and SCL were strongly associated with this response. In the latter finding, age was a prominent factor. Additional analyses supported the idea that the interaction of autonomic and endocrine reactivity is subject to natural development. These findings provide evidence that adolescence might be a period of highly interactive emotional–neurobiological development, particularly with respect to the development of stress management skills.
Postoperative Pain Management in Children Undergoing Laparoscopic Appendectomy: A Scoping Review
Authors: Alsharari Abdalkarem Fedgash , Alshammari Farhan Faleh , Salihu Dauda , Alruwaili Majed Mowanes
Published: March 2023

Laparoscopic appendectomy (LA) is one of the most commonly performed surgical procedures in children and is associated with extreme postoperative discomfort due to peritoneal inflammation and infection. The main objective of this study was to investigate the effects of postoperative pain (POP) in children after laparoscopic appendectomy. Articles describing or evaluating the control of POP in children with LA were considered eligible. All available literature such as randomized controls, prospective controls, retrospective as well as clinical studies were considered. A comprehensive search was performed in PubMed, Medline, Embase, Cochrane Library, Clinical trials.gov, and Google scholar. The initial search took place on 23 April 2021, and was updated on 24 August 2021. There were no language or date restrictions. Each of the included articles was evaluated separately by two independent reviewers. Additional papers were found by searching the reference lists of eligible studies. Eighteen papers were considered. All papers, and many of them used different methods to treat POP in children undergoing LA, such as lidocaine infusion, different analgesic approaches, ultrasound-guided transverse abdominis blockade (UGTAP), ultrasound-guided quadratus lumborum blockade (UGQLB), and comparison of open appendectomy (OA) with local anesthetics in relation to POP management in children. Laparoscopic appendectomy is the surgical procedure preferred by clinicians compared with open appendectomy in children. A multimodal analgesic approach is optimal and efficient surgical techniques such as UGBRSB, UGQLB, and UGTAP block might significantly impact POP in children except that there are contraindications. Dexmedetomidine proved to be an effective adjuvant that can enhance the effect of local anesthetics. The lack of a sufficient number of studies may be a factor affecting our confidence in the results of this study. Therefore, further evidence-based randomized control trials with a large sample size are needed to provide clarity.
Development of the Scale for Measuring Perceived Daily Life Disruption
Authors: Remr Jiri
Published: March 2023

The measures that were taken in many countries as a response to the COVID-19 pandemic not only brought about new stimuli in the lives of individuals, but also gave rise to various restrictions that led to discontinuities in many aspects of daily life. Therefore, the development of a sound measure for monitoring the level of perceived daily life disruption is important. The Perceived Daily Life Disruption (PDLD) scale is proposed and its initial validation based on the assessment of key psychometric properties is targeted in this study. A confirmatory factor analysis (CFA) on the PDLD scale was conducted on a representative sample (n = 1372). In addition, univariate statistics were calculated, internal consistency was tested, and unidimensionality based on principal component analysis was performed. The CFA yielded satisfactory results concerning the standard indices and achieved a high internal consistency. It was observed that the scale adequately differentiates the level of perceived daily life disruption among diverse subpopulations. Usage of the PDLD scale can be recommended; it is easy to administer and it yields acceptable results.
Sustainable Development of Underground Coal Resources in Shallow Groundwater Areas for Environment and Socio-Economic Considerations: A Case Study of Zhangji Coal Mine in China
Authors: Zhang Ruiya , Chugh Yoginder P.
Published: March 2023

Coal resources in China are developed in several regions with shallow groundwater, and large mining-related surface subsidence can have negative impacts on agriculture, land and water resources as well as existing and future socio-economic resources. All these are important for sustainable resource development. Dynamic subsidence reclamation (DSR) planning concepts are evaluated here for another case study with analyses over a 11-year period. In DSR topsoil, subsoil, farming, and water resources management are dynamically synergized concurrent with mining ahead of and behind the projected dynamic subsidence trough. The study area involved mining five longwall faces (and post-mining reclamation) to assess if DSR could have improved both the environment and socio-economic conditions for post-mining land use as compared to using traditional reclamation (TR) and TR-modified (TR(MOD)) approaches. The results show that: (1) Upon final reclamation, farmland area and water resources in DSR and TR (MOD) will have increased by 5.6% and 30.2% as compared to TR. Removing soils ahead of mining before they submerge into water is important for farmland reclamation and long-term economic development. (2) Due to topsoil and subsoil separation and storage in the DSR plan, reclaimed farmland productivity should recover quickly and agriculture production should be larger than TR and TR(MOD) plans. (3) For a simplified economic model, the total revenue in the DSR plan should be 2.8 times more than in TR and 1.2 times larger than in TR (MOD) plan. (4) The total net revenue of the TR(MOD) plan should be increased by 8.1% as compared with the TR plan. The benefits will be much greater for analyses over longer periods. Overall, the DSR plan will allow for an improved socio-economic environment for new businesses to support disrupted workforces during and after mining.
State of the Art of the Molecular Biology of the Interaction between Cocoa and Witches’ Broom Disease: A Systematic Review
Authors: Santos Ariana Silva , Mora-Ocampo Irma Yuliana , de Novais Diogo Pereira Silva , Aguiar Eric Roberto Guimarães Rocha , Pirovani Carlos Priminho
Published: March 2023

Significant scientific advances to elucidate the Moniliophthora perniciosa pathosystem have been achieved in recent years, but the molecular biology of this pathogen-host interaction is still a field with many unanswered questions. In order to present insights at the molecular level, we present the first systematic review on the theme. All told, 1118 studies were extracted from public databases. Of these, 109 were eligible for the review, based on the inclusion and exclusion criteria. The results indicated that understanding the transition from the biotrophic-necrotrophic phase of the fungus is crucial for control of the disease. Proteins with strong biotechnological potential or that can be targets for pathosystem intervention were identified, but studies regarding possible applications are still limited. The studies identified revealed important genes in the M. perniciosa-host interaction and efficient molecular markers in the search for genetic variability and sources of resistance, with Theobroma cacao being the most common host. An arsenal of effectors already identified and not explored in the pathosystem were highlighted. This systematic review contributes to the understanding of the pathosystem at the molecular level, offering new insights and proposing different paths for the development of new strategies to control witches’ broom disease.
Synthesis of Manganese Zinc Ferrite Nanoparticles in Medical-Grade Silicone for MRI Applications
Authors: Stoll Joshua A. , Lachowicz Dorota , Kmita Angelika , Gajewska Marta , Sikora Marcin , Berent Katarzyna , Przybylski Marek , Russek Stephen E. , Celinski Zbigniew J. , Hankiewicz Janusz H.
Published: March 2023

The aim of this project is to fabricate hydrogen-rich silicone doped with magnetic nanoparticles for use as a temperature change indicator in magnetic resonance imaging-guided (MRIg) thermal ablations. To avoid clustering, the particles of mixed MnZn ferrite were synthesized directly in a medical-grade silicone polymer solution. The particles were characterized by transmission electron microscopy, powder X-ray diffraction, soft X-ray absorption spectroscopy, vibrating sample magnetometry, temperature-dependent nuclear magnetic resonance relaxometry (20 °C to 60 °C, at 3.0 T), and magnetic resonance imaging (at 3.0 T). Synthesized nanoparticles were the size of 4.4 nm ± 2.1 nm and exhibited superparamagnetic behavior. Bulk silicone material showed a good shape stability within the study’s temperature range. Embedded nanoparticles did not influence spin–lattice relaxation, but they shorten the longer component of spin–spin nuclear relaxation times of silicone’s protons. However, these protons exhibited an extremely high r2* relaxivity (above 1200 L s−1 mmol−1) due to the presence of particles, with a moderate decrease in the magnetization with temperature. With an increased temperature decrease of r2*, this ferro–silicone can be potentially used as a temperature indicator in high-temperature MRIg ablations (40 °C to 60 °C).
CAR T-Cell Persistence Correlates with Improved Outcome in Patients with B-Cell Lymphoma
Authors: Wittibschlager Valerie , Bacher Ulrike , Seipel Katja , Porret Naomi , Wiedemann Gertrud , Haslebacher Claudia , Hoffmann Michèle , Daskalakis Michael , Akhoundova Dilara , Pabst Thomas
Published: March 2023

Chimeric antigen receptor (CAR) T-cell therapy has led to profound and durable tumor responses in a relevant subset of patients with relapsed/refractory (r/r) B-cell lymphomas. Still, some patients show insufficient benefit or relapse after CAR T-cell therapy. We performed a retrospective study to investigate the correlation between CAR T-cell persistence in the peripheral blood (PB) at 6 months, assessed by droplet digital PCR (ddPCR), with CAR T-cell treatment outcome. 92 patients with r/r B-cell lymphomas were treated with CD19-targeting CAR T-cell therapies at our institution between 01/2019–08/2022. Six months post-treatment, 15 (16%) patients had no detectable circulating CAR-T constructs by ddPCR. Patients with CAR T-cell persistence had a significantly higher CAR T-cell peak (5432 vs. 620 copies/ug cfDNA, p = 0.0096), as well as higher incidence of immune effector cell-associated neurotoxicity syndrome (37% vs. 7%, p = 0.0182). After a median follow-up of 8.5 months, 31 (34%) patients relapsed. Lymphoma relapses were less frequent among patients with CAR T-cell persistence (29% vs. 60%, p = 0.0336), and CAR T-cell persistence in the PB at 6 months was associated with longer progression-free survival (PFS) (HR 2.79, 95% CI: 1.09–7.11, p = 0.0319). Moreover, we observed a trend towards improved overall survival (OS) (HR 1.99, 95% CI: 0.68–5.82, p = 0.2092) for these patients. In our cohort of 92 B-cell lymphomas, CAR T-cell persistence at 6 months was associated with lower relapse rates and longer PFS. Moreover, our data confirm that 4-1BB-CAR T-cells have a longer persistence as compared to CD-28-based CAR T-cells.
Adipose-Derived Stem Cells in Reinforced Collagen Gel: A Comparison between Two Approaches to Differentiation towards Smooth Muscle Cells
Authors: Filova Elena , Supova Monika , Eckhardt Adam , Vrbacky Marek , Blanquer Andreu , Travnickova Martina , Knitlova Jarmila , Suchy Tomas , Ryglova Sarka , Braun Martin , Burdikova Zuzana , Schätz Martin , Jencova Vera , Lisnenko Maxim , Behalek Lubos , Prochazkova Renata , Sedlacek Radek , Kubasova Kristyna , Bacakova Lucie
Published: March 2023

Scaffolds made of degradable polymers, such as collagen, polyesters or polysaccharides, are promising matrices for fabrication of bioartificial vascular grafts or patches. In this study, collagen isolated from porcine skin was processed into a gel, reinforced with collagen particles and with incorporated adipose tissue-derived stem cells (ASCs). The cell-material constructs were then incubated in a DMEM medium with 2% of FS (DMEM_part), with added polyvinylalcohol nanofibers (PVA_part sample), and for ASCs differentiation towards smooth muscle cells (SMCs), the medium was supplemented either with human platelet lysate released from PVA nanofibers (PVA_PL_part) or with TGF-β1 + BMP-4 (TGF + BMP_part). The constructs were further endothelialised with human umbilical vein endothelial cells (ECs). The immunofluorescence staining of alpha-actin and calponin, and von Willebrand factor, was performed. The proteins involved in cell differentiation, the extracellular matrix (ECM) proteins, and ECM remodelling proteins were evaluated by mass spectrometry on day 12 of culture. Mechanical properties of the gels with ASCs were measured via an unconfined compression test on day 5. Gels evinced limited planar shrinkage, but it was higher in endothelialised TGF + BMP_part gel. Both PVA_PL_part samples and TGF + BMP_part samples supported ASC growth and differentiation towards SMCs, but only PVA_PL_part supported homogeneous endothelialisation. Young modulus of elasticity increased in all samples compared to day 0, and PVA_PL_part gel evinced a slightly higher ratio of elastic energy. The results suggest that PVA_PL_part collagen construct has the highest potential to remodel into a functional vascular wall.
MicroRNAs as Biomarkers of Surgical Outcome in Mesial Temporal Lobe Epilepsy: A Systematic Review
Authors: Yakimov Alexey M. , Timechko Elena E. , Areshkina Irina G. , Usoltseva Anna A. , Yakovleva Kristina D. , Kantimirova Elena A. , Utyashev Nikita , Ivin Nikita , Dmitrenko Diana V.
Published: March 2023

Mesial temporal lobe epilepsy is the most common type of epilepsy. For most patients suffering from TLE, the only treatment option is surgery. However, there is a high possibility of relapse. Invasive EEG as a method for predicting the outcome of surgical treatment is a very complex and invasive manipulation, so the search for outcome biomarkers is an urgent task. MicroRNAs as potential biomarkers of surgical outcome are the subject of this study. For this study, a systematic search for publications in databases such as PubMed, Springer, Web of Science, Scopus, ScienceDirect, and MDPI was carried out. The following keywords were used: temporal lobe epilepsy, microRNA, biomarkers, surgery, and outcome. Three microRNAs were studied as prognostic biomarkers of surgical outcome: miR-27a-3p, miR-328-3p, and miR-654-3p. According to the results of the study, only miR-654-3p showed a good ability to discriminate between patients with poor and good surgical outcomes. MiR-654-3p is involved in the following biological pathways: ATP-binding cassette drug transporters, glutamate transporter SLC7A11, and TP53. A specific target for miR-654-3p is GLRA2, the glycine receptor subunit. MicroRNAs, which are diagnostic biomarkers of TLE, and epileptogenesis, miR-134-5p, MiR-30a, miRs-143, etc., can be considered as potential biomarkers of surgical outcome, as they can be indicators of early and late relapses. These microRNAs are involved in the processes characteristic of epilepsy: oxidative stress and apoptosis. The study of miRNAs as potential predictive biomarkers of surgical outcome is an urgent task and should be continued. However, when studying miRNA expression profiles, it is important to take into account and note a number of factors, such as the type of sample under study, the time of sampling for the study, the type and duration of the disease, and the type of antiepileptic treatment. Without taking into account all these factors, it is impossible to assess the influence and involvement of miRNAs in epileptic processes.
Cinnamomum zeylanicum Blume Essential Oil Inhibits Metastatic Melanoma Cell Proliferation by Triggering an Incomplete Tumour Cell Stress Response
Authors: Cappelli Giulia , Giovannini Daniela , Vilardo Laura , Basso Annalisa , Iannetti Ilaria , Massa Marianna , Ruberto Giuseppe , Muir Ryan , Pastore Carlo , D’Agnano Igea , Mariani Francesca
Published: March 2023

Given the known pro-oxidant status of tumour cells, the development of anti-proliferative strategies focuses on products with both anti- and pro-oxidant properties that can enhance antitumour drug cytotoxicity. We used a C. zeylanicum essential oil (CINN-EO) and assessed its effect on a human metastatic melanoma cell line (M14). Human PBMCs and MDMs from healthy donors were used as normal control cells. CINN-EO induced cell growth inhibition, cell cycle perturbation, ROS and Fe(II) increases, and mitochondrial membrane depolarization. To assess whether CINN-EO could affect the stress response, we analysed iron metabolism and stress response gene expression. CINN-EO increased HMOX1, FTH1, SLC7A11, DGKK, and GSR expression but repressed OXR1, SOD3, Tf, and TfR1 expression. HMOX1, Fe(II), and ROS increases are associated with ferroptosis, which can be reversed by SnPPIX, an HMOX1 inhibitor. Indeed, our data demonstrated that SnPPIX significantly attenuated the inhibition of cell proliferation, suggesting that the inhibition of cell proliferation induced by CINN-EO could be related to ferroptosis. Concurrent treatment with CINN-EO enhanced the anti-melanoma effect of two conventional antineoplastic drugs: the mitochondria-targeting tamoxifen and the anti-BRAF dabrafenib. We demonstrate that CINN-EO-mediated induction of an incomplete stress response specifically in cancer cells affects the proliferation of melanoma cells and can enhance drug cytotoxicity.
High Resolution and Automatable Cytogenetic Biodosimetry Using In Situ Telomere and Centromere Hybridization for the Accurate Detection of DNA Damage: An Overview
Authors: M’Kacher Radhia , Colicchio Bruno , Junker Steffen , El Maalouf Elie , Heidingsfelder Leonhard , Plesch Andreas , Dieterlen Alain , Jeandidier Eric , Carde Patrice , Voisin Philippe
Published: March 2023

In the event of a radiological or nuclear accident, or when physical dosimetry is not available, the scoring of radiation-induced chromosomal aberrations in lymphocytes constitutes an essential tool for the estimation of the absorbed dose of the exposed individual and for effective triage. Cytogenetic biodosimetry employs different cytogenetic assays including the scoring of dicentrics, micronuclei, and translocations as well as analyses of induced premature chromosome condensation to define the frequency of chromosome aberrations. However, inherent challenges using these techniques include the considerable time span from sampling to result, the sensitivity and specificity of the various techniques, and the requirement of highly skilled personnel. Thus, techniques that obviate these challenges are needed. The introduction of telomere and centromere (TC) staining have successfully met these challenges and, in addition, greatly improved the efficiency of cytogenetic biodosimetry through the development of automated approaches, thus reducing the need for specialized personnel. Here, we review the role of the various cytogenetic dosimeters and their recent improvements in the management of populations exposed to genotoxic agents such as ionizing radiation. Finally, we discuss the emerging potentials to exploit these techniques in a wider spectrum of medical and biological applications, e.g., in cancer biology to identify prognostic biomarkers for the optimal triage and treatment of patients.
Rhizosphere Fungal Dynamics in Sugarcane during Different Growth Stages
Authors: Liu Qiang , Pang Ziqin , Liu Yueming , Fallah Nyumah , Hu Chaohua , Lin Wenxiong , Yuan Zhaonian
Published: March 2023

Understanding the normal variation of the sugarcane rhizosphere fungal community throughout its life cycle is essential for the development of agricultural practices for fungal and ecological health associated with the microbiota. Therefore, we performed high-throughput sequencing of 18S rDNA of soil samples using the Illumina sequencing platform for correlation analysis of rhizosphere fungal community time series, covering information from 84 samples in four growth periods. The results revealed that the sugarcane rhizosphere fungi possessed the maximum fungal richness in Tillering. Rhizosphere fungi were closely associated with sugarcane growth, including Ascomycota, Basidiomycota, and Chytridiomycota, which showed high abundance in a stage-specific manner. Through the Manhattan plots, 10 fungal genera showed a decreasing trend throughout the sugarcane growth, and two fungal genera were significantly enriched at three stages of sugarcane growth (p < 0.05) including Pseudallescheria (Microascales, Microascaceae) and Nectriaceae (Hypocreales, Nectriaceae). In addition, soil pH, soil temperature, total nitrogen, and total potassium were critical drivers of fungal community structure at different stages of sugarcane growth. We also found that sugarcane disease status showed a significant and strong negative effect on selected soil properties by using structural equation modeling (SEM), suggesting that poor soil increases the likelihood of sugarcane disease. In addition, the assembly of sugarcane rhizosphere fungal community structure was mainly influenced by stochastic factors, but after the sugarcane root system became stable (Maturity), the stochastic contribution rate decreased to the lowest value. Our work provides a more extensive and solid basis for the biological control of sugarcane potential fungal diseases.
Adipose Mesenchymal Stromal Cell-Derived Exosomes Carrying MiR-122-5p Antagonize the Inhibitory Effect of Dihydrotestosterone on Hair Follicles by Targeting the TGF-β1/SMAD3 Signaling Pathway
Authors: Liang Yunxiao , Tang Xin , Zhang Xue , Cao Cuixiang , Yu Miao , Wan Miaojian
Published: March 2023

Androgenic alopecia (AGA) is the most common type of hair loss, where local high concentrations of dihydrotestosterone (DHT) in the scalp cause progressive shrinkage of the hair follicles, eventually contributing to hair loss. Due to the limitations of existing methods to treat AGA, the use of multi-origin mesenchymal stromal cell-derived exosomes has been proposed. However, the functions and mechanisms of action of exosomes secreted by adipose mesenchymal stromal cells (ADSCs-Exos) in AGA are still unclear. Using Cell Counting Kit-8 (CCK8) analysis, immunofluorescence staining, scratch assays, and Western blotting, it was found that ADSC-Exos contributed to the proliferation, migration, and differentiation of dermal papilla cells (DPCs) and up-regulated the expression of cyclin, β-catenin, versican, and BMP2. ADSC-Exos also mitigated the inhibitory effects of DHT on DPCs and down-regulated transforming growth factor-beta1 (TGF-β1) and its downstream genes. Moreover, high-throughput miRNA sequencing and bioinformatics analysis identified 225 genes that were co-expressed in ADSC-Exos; of these, miR-122-5p was highly enriched and was found by luciferase assays to target SMAD3. ADSC-Exos carrying miR-122-5p antagonized DHT inhibition of hair follicles, up-regulated the expression of β-catenin and versican in vivo and in vitro, restored hair bulb size and dermal thickness, and promoted the normal growth of hair follicles. So, ADSC-Exos enhanced the regeneration of hair follicles in AGA through the action of miR-122-5p and the inhibition of the TGF-β/SMAD3 axis. These results suggest a novel treatment option for the treatment of AGA.
High Expression of COA6 Is Related to Unfavorable Prognosis and Enhanced Oxidative Phosphorylation in Lung Adenocarcinoma
Authors: Zhang Ming , Liao Xiaohua , Ji Guanxu , Fan Xianming , Wu Qiang
Published: March 2023

Mitochondrial metabolism plays an important role in the occurrence and development of cancers. Cytochrome C oxidase assembly factor six (COA6) is essential in mitochondrial metabolism. However, the role of COA6 in lung adenocarcinoma (LUAD) remains unknown. Here we report that the expression of COA6 mRNA and protein were upregulated in LUAD tissues compared with lung normal tissues. We found that COA6 had high sensitivity and specificity to distinguish LUAD tissues from normal lung tissues shown by a receiver operating characteristic (ROC) curve. In addition, our univariate and multivariate Cox regression analysis indicated that COA6 was an independent unfavorable prognostic factor for LUAD patients. Furthermore, our survival analysis and nomogram showed that a high expression of COA6 mRNA was related to the short overall survival (OS) of LUAD patients. Notably, our weighted correlation network analysis (WGCNA) and functional enrichment analysis revealed that COA6 may participate in the development of LUAD by affecting mitochondrial oxidative phosphorylation (OXPHOS). Importantly, we demonstrated that depletion of COA6 could decrease the mitochondrial membrane potential (MMP), nicotinamide adenine dinucleotide (NAD) + hydrogen (H) (NADH), and adenosine triphosphate (ATP) production in LUAD cells (A549 and H1975), hence inhibiting the proliferation of these cells in vitro. Together, our study strongly suggests that COA6 is significantly associated with the prognosis and OXPHOS in LUAD. Hence, COA6 is highly likely a novel prognostic biomarker and therapeutic target of LUAD.
Analysis of Genome Structure and Its Variations in Potato Cultivars Grown in Russia
Authors: Karetnikov Dmitry I. , Vasiliev Gennady V. , Toshchakov Stepan V. , Shmakov Nikolay A. , Genaev Mikhail A. , Nesterov Mikhail A. , Ibragimova Salmaz M. , Rybakov Daniil A. , Gavrilenko Tatjana A. , Salina Elena A. , Patrushev Maxim V. , Kochetov Alex V. , Afonnikov Dmitry A.
Published: March 2023

Solanum tuberosum L. (common potato) is one of the most important crops produced almost all over the world. Genomic sequences of potato opens the way for studying the molecular variations related to diversification. We performed a reconstruction of genomic sequences for 15 tetraploid potato cultivars grown in Russia using short reads. Protein-coding genes were identified; conserved and variable parts of pan-genome and the repertoire of the NBS-LRR genes were characterized. For comparison, we used additional genomic sequences for twelve South American potato accessions, performed analysis of genetic diversity, and identified the copy number variations (CNVs) in two these groups of potato. Genomes of Russian potato cultivars were more homogeneous by CNV characteristics and have smaller maximum deletion size in comparison with South American ones. Genes with different CNV occurrences in two these groups of potato accessions were identified. We revealed genes of immune/abiotic stress response, transport and five genes related to tuberization and photoperiod control among them. Four genes related to tuberization and photoperiod were investigated in potatoes previously (phytochrome A among them). A novel gene, homologous to the poly(ADP-ribose) glycohydrolase (PARG) of Arabidopsis, was identified that may be involved in circadian rhythm control and contribute to the acclimatization processes of Russian potato cultivars.
Synthesis, Characterization and Biological Investigation of the Platinum(IV) Tolfenamato Prodrug–Resolving Cisplatin-Resistance in Ovarian Carcinoma Cell Lines
Authors: Barth Marie-Christin , Häfner Norman , Runnebaum Ingo B. , Weigand Wolfgang
Published: March 2023

The research on the anticancer potential of platinum(IV) complexes represents one strategy to circumvent the deficits of approved platinum(II) drugs. Regarding the role of inflammation during carcinogenesis, the effects of non-steroidal anti-inflammatory drug (NSAID) ligands on the cytotoxicity of platinum(IV) complexes is of special interest. The synthesis of cisplatin- and oxaliplatin-based platinum(IV) complexes with four different NSAID ligands is presented in this work. Nine platinum(IV) complexes were synthesized and characterized by use of nuclear magnetic resonance (NMR) spectroscopy (1H, 13C, 195Pt, 19F), high-resolution mass spectrometry, and elemental analysis. The cytotoxic activity of eight compounds was evaluated for two isogenic pairs of cisplatin-sensitive and -resistant ovarian carcinoma cell lines. Platinum(IV) fenamato complexes with a cisplatin core showed especially high in vitro cytotoxicity against the tested cell lines. The most promising complex, 7, was further analyzed for its stability in different buffer solutions and behavior in cell cycle and cell death experiments. Compound 7 induces a strong cytostatic effect and cell line-dependent early apoptotic or late necrotic cell death processes. Gene expression analysis suggests that compound 7 acts through a stress-response pathway integrating p21, CHOP, and ATF3.
Investigating Circular RNAs Using qRT-PCR; Roundup of Optimization and Processing Steps
Authors: Drula Rares , Braicu Cornelia , Chira Sergiu , Berindan-Neagoe Ioana
Published: March 2023

Circular RNAs (circRNAs) have gained recent attraction due to their functional versatility and particular structure connected to human diseases. Current investigations are focused on the interplay between their ability to sponge smaller species of RNAs, such as microRNAs (miRNAs), thus influencing their regulatory activity on gene expression and protein templates. Therefore, their reported implication in various biological processes axis has resulted in an accumulating number of studies. While the testing and annotation methods of novel circular transcripts are still under development, there is still a plethora of transcript candidates suitable for investigation in human disease. The discordance in the literature regarding the approaches used in circRNAs quantification and validation methods, especially regarding qRT-PCR, the current golden standard procedure, leads to high result variability and undermines the replicability of the studies. Therefore, our study will offer several valuable insights into bioinformatic data for experimental design for circRNA investigation and in vitro aspects. Specifically, we will highlight key aspects such as circRNA database annotation divergent primer design and several processing steps, such as RNAse R treatment optimization and circRNA enrichment assessment. Additionally, we will provide insights into the exploration of circRNA-miRNA interactions, a prerequisite for further functional investigations. With this, we aim to contribute to the methodological consensus in a currently expanding field with possible implications for assessing therapeutic targets and biomarker discovery.
Harnessing Fc/FcRn Affinity Data from Patents with Different Machine Learning Methods
Authors: Dumet Christophe , Pugnière Martine , Henriquet Corinne , Gouilleux-Gruart Valérie , Poupon Anne , Watier Hervé
Published: March 2023

Monoclonal antibodies are biopharmaceuticals with a very long half-life due to the binding of their Fc portion to the neonatal receptor (FcRn), a pharmacokinetic property that can be further improved through engineering of the Fc portion, as demonstrated by the approval of several new drugs. Many Fc variants with increased binding to FcRn have been found using different methods, such as structure-guided design, random mutagenesis, or a combination of both, and are described in the literature as well as in patents. Our hypothesis is that this material could be subjected to a machine learning approach in order to generate new variants with similar properties. We therefore compiled 1323 Fc variants affecting the affinity for FcRn, which were disclosed in twenty patents. These data were used to train several algorithms, with two different models, in order to predict the affinity for FcRn of new randomly generated Fc variants. To determine which algorithm was the most robust, we first assessed the correlation between measured and predicted affinity in a 10-fold cross-validation test. We then generated variants by in silico random mutagenesis and compared the prediction made by the different algorithms. As a final validation, we produced variants, not described in any patents, and compared the predicted affinity with the experimental binding affinities measured by surface plasmon resonance (SPR). The best mean absolute error (MAE) between predicted and experimental values was obtained with a support vector regressor (SVR) using six features and trained on 1251 examples. With this setting, the error on the log(KD) was less than 0.17. The obtained results show that such an approach could be used to find new variants with better half-life properties that are different from those already extensively used in therapeutic antibody development.
SEM Observation of the Filter after Administration of Blinatumomab: A Possibility of Leakage during Home Administration Using a Portable Infusion Pump
Authors: Takano Megumi , Inoue Motoki , Ikeda Yuko , Kage Hidenori , Inokawa Tohru , Nakadate Kazuhiko , Yasu Takeo , Tsuda Yasumasa , Goto Kazumi
Published: March 2023

Blinatumomab (Blincyto® injection solution) is classified as a bispecific T-cell engaging (BiTE) antibody and is intended for the treatment of relapsed/refractory acute lymphoblastic leukemia. It requires continuous infusion to maintain therapeutic levels. Therefore, it is often administered at home. Monoclonal antibodies, which are administered intravenously, have the potential to leak depending on the nature of the administration devices. Therefore, we investigated device-associated causes of blinatumomab leakage. We observed no apparent changes to the filter and its materials after exposure to the injection solution and surfactant. From scanning electron microscopic images, precipitate on the surface of the filters was observed after physical stimulation of the injection solution. Therefore, physical stimulations should be avoided during the prolonged administration of blinatumomab. In conclusion, the findings of this study assist in the safe administration of antibodies using portable infusion pumps, taking into consideration the composition of drug excipients and the choice of filter type and structure.