bluuebunny/crossref_metadata_2025_split huggingface dataset:
Repurposing dimethyl fumarate as an antiepileptogenic and disease-modifying treatment for drug-resistant epilepsy
Authors: Sandouka Sereen , Singh Prince Kumar , Saadi Aseel , Taiwo Rhoda Olowe , Sheeni Yara , Zhang Taige , Deeb Larin , Guignet Michelle , White Steve H. , Shekh-Ahmad Tawfeeq 
Published: November 2023

Abstract
Background
Epilepsy affects over 65 million people worldwide and significantly burdens patients, caregivers, and society. Drug-resistant epilepsy occurs in approximately 30% of patients and growing evidence indicates that oxidative stress contributes to the development of such epilepsies. Activation of the Nrf2 pathway, which is involved in cellular defense, offers a potential strategy for reducing oxidative stress and epilepsy treatment. Dimethyl fumarate (DMF), an Nrf2 activator, exhibits antioxidant and anti-inflammatory effects and is used to treat multiple sclerosis.

Methods
The expression of Nrf2 and its related genes in vehicle or DMF treated rats were determined via RT-PCR and Western blot analysis. Neuronal cell death was evaluated by immunohistochemical staining. The effects of DMF in preventing the onset of epilepsy and modifying the disease were investigated in the kainic acid-induced status epilepticus model of temporal lobe epilepsy in rats.
The open field, elevated plus maze and T-Maze spontaneous alteration tests were used for behavioral assessments.

Results
We demonstrate that administration of DMF following status epilepticus increased Nrf2 activity, attenuated status epilepticus-induced neuronal cell death, and decreased seizure frequency and the total number of seizures compared to vehicle-treated animals. Moreover, DMF treatment reversed epilepsy-induced behavioral deficits in the treated rats.
Moreover, DMF treatment even when initiated well after the diagnosis of epilepsy, reduced symptomatic seizures long after the drug was eliminated from the body.

Conclusions
Taken together, these findings suggest that DMF, through the activation of Nrf2, has the potential to serve as a therapeutic target for preventing epileptogenesis and modifying epilepsy.
Characterization of intrinsic and effective fitness changes caused by temporarily fixed mutations in the SARS-CoV-2 spike E484 epitope and identification of an epistatic precondition for the evolution of E484A in variant Omicron
Authors: Schröder Simon , Richter Anja , Veith Talitha , Emanuel Jackson , Gudermann Luca , Friedmann Kirstin , Jeworowski Lara M. , Mühlemann Barbara , Jones Terry C. , Müller Marcel A. , Corman Victor M. , Drosten Christian 
Published: November 2023

Abstract
Background
Intrinsic fitness costs are likely to have guided the selection of lineage-determining mutations during emergence of variants of SARS-CoV-2. Whereas changes in receptor affinity and antibody neutralization have been thoroughly mapped for individual mutations in spike, their influence on intrinsic replicative fitness remains understudied.

Methods
We analyzed mutations in immunodominant spike epitope E484 that became temporarily fixed over the pandemic. We engineered the resulting immune escape mutations E484K, -A, and -Q in recombinant SARS-CoV-2. We characterized viral replication, entry, and competitive fitness with and without immune serum from humans with defined exposure/vaccination history and hamsters monospecifically infected with the E484K variant. We additionally engineered a virus containing the Omicron signature mutations N501Y and Q498R that were predicted to epistatically enhance receptor binding.

Results
Multistep growth kinetics in Vero-, Calu-3, and NCI-H1299 were identical between viruses. Synchronized entry experiments based on cold absorption and temperature shift identified only an insignificant trend toward faster entry of the E484K variant. Competitive passage experiments revealed clear replicative fitness differences. In absence of immune serum, E484A and E484Q, but not E484K, were replaced by wildtype (WT) in competition assays. In presence of immune serum, all three mutants outcompeted WT. Decreased E484A fitness levels were over-compensated for by N501Y and Q498R, identifying a putative Omicron founder background that exceeds the intrinsic and effective fitness of WT and matches that of E484K. Critically, the E484A/Q498R/N501Y mutant and E484K have equal fitness also in presence of pre-Omicron vaccinee serum, whereas the fitness gain by E484K is lost in the presence of serum raised against the E484K variant in hamsters.

Conclusions
The emergence of E484A and E484Q prior to widespread population immunity may have been limited by fitness costs. In populations already exposed to the early immune escape epitope E484K, the Omicron founder background may have provided a basis for alternative immune escape evolution via E484A. Studies of major antigenic epitope changes with and without their epistatic context help reconstruct the sequential adjustments of intrinsic fitness versus neutralization escape during the evolution of major SARS-CoV-2 variants in an increasingly immune human population.
Machine learning provides specific detection of salt and drought stresses in cucumber based on miRNA characteristics
Authors: Mohammadi Parvin , Asefpour Vakilian Keyvan 
Published: November 2023

Abstract
Background
Specific detection of the type and severity of plant abiotic stresses helps prevent yield loss by considering timely actions. This study introduces a novel method to detect the type and severity of stress in cucumber plants under salinity and drought conditions. Various features, i.e., morphological (image textural features), physiological/biochemical (relative water content, chlorophyll, catalase activity, anthocyanins, phenol content, and proline), as well as miRNA characteristics (the concentration of miRNA-156a, miRNA-166i, miRNA-399g, and miRNA-477b) were extracted from plant leaves, and machine learning methods were used to predict the type and severity of stress by having these features. Support vector machine (SVM) with parameters optimized by genetic algorithm (GA) and particle swarm optimization (PSO) was used for machine learning.

Results
The coefficient of determination of predicting the stress type and severity in plants under both stresses was 0.61, 0.82, and 0.99 using morphological, physiological/biochemical, and miRNA characteristics, respectively. This reveals machine learning methods optimized by metaheuristic optimization techniques can provide specific detection of salt and drought stresses in cucumber plants based on miRNA characteristics. Among the study miRNAs, miRNA-477b and miRNA-399g had the highest and lowest contribution to salt and drought stresses, respectively.

Conclusions
Comapred to conventional plant traits, miRNAs are more reliable features for providing us with valuable information about plant abiotic diseases at early stages. Using an electrochemical miRNA biosensor similar to one used in this work to measure the miRNA concentration in plant leaves and using a machine learning algorithm such as SVM enable farmers to detect the salt and drought stress at early stages in cucumber plants with very high accuracy.
Relative timing information and orthology in evolutionary scenarios
Authors: Schaller David , Hartmann Tom , Lafond Manuel , Stadler Peter F. , Wieseke Nicolas , Hellmuth Marc 
Published: November 2023

Abstract
Background
Evolutionary scenarios describing the evolution of a family of genes within a collection of species comprise the mapping of the vertices of a gene tree T to vertices and edges of a species tree S. The relative timing of the last common ancestors of two extant genes (leaves of T) and the last common ancestors of the two species (leaves of S) in which they reside is indicative of horizontal gene transfers (HGT) and ancient duplications. Orthologous gene pairs, on the other hand, require that their last common ancestors coincides with a corresponding speciation event. The relative timing information of gene and species divergences is captured by three colored graphs that have the extant genes as vertices and the species in which the genes are found as vertex colors: the equal-divergence-time (EDT) graph, the later-divergence-time (LDT) graph and the prior-divergence-time (PDT) graph, which together form an edge partition of the complete graph.

Results
Here we give a complete characterization in terms of informative and forbidden triples that can be read off the three graphs and provide a polynomial time algorithm for constructing an evolutionary scenario that explains the graphs, provided such a scenario exists. While both LDT and PDT graphs are cographs, this is not true for the EDT graph in general. We show that every EDT graph is perfect. While the information about LDT and PDT graphs is necessary to recognize EDT graphs in polynomial-time for general scenarios, this extra information can be dropped in the HGT-free case. However, recognition of EDT graphs without knowledge of putative LDT and PDT graphs is NP-complete for general scenarios. In contrast, PDT graphs can be recognized in polynomial-time. We finally connect the EDT graph to the alternative definitions of orthology that have been proposed for scenarios with horizontal gene transfer. With one exception, the corresponding graphs are shown to be colored cographs.
Mechanism and therapeutic potential of targeting cGAS-STING signaling in neurological disorders
Authors: Huang Yige , Liu Bangyan , Sinha Subhash C. , Amin Sadaf , Gan Li 
Published: November 2023

AbstractDNA sensing is a pivotal component of the innate immune system that is responsible for detecting mislocalized DNA and triggering downstream inflammatory pathways. Among the DNA sensors, cyclic GMP-AMP synthase (cGAS) is a primary player in detecting cytosolic DNA, including foreign DNA from pathogens and self-DNA released during cellular damage, culminating in a type I interferon (IFN-I) response through stimulator of interferon genes (STING) activation. IFN-I cytokines are essential in mediating neuroinflammation, which is widely observed in CNS injury, neurodegeneration, and aging, suggesting an upstream role for the cGAS DNA sensing pathway. In this review, we summarize the latest developments on the cGAS-STING DNA-driven immune response in various neurological diseases and conditions. Our review covers the current understanding of the molecular mechanisms of cGAS activation and highlights cGAS-STING signaling in various cell types of central and peripheral nervous systems, such as resident brain immune cells, neurons, and glial cells. We then discuss the role of cGAS-STING signaling in different neurodegenerative conditions, including tauopathies, Alzheimer’s disease, Parkinson’s disease, and amyotrophic lateral sclerosis, as well as aging and senescence. Finally, we lay out the current advancements in research and development of cGAS inhibitors and assess the prospects of targeting cGAS and STING as therapeutic strategies for a wide spectrum of neurological diseases.
Evaluation of human papillomavirus DNA in colorectal cancer and adjacent mucosal tissue samples
Authors: Galati Luisa , Gupta Purnima , Tufaro Antonio , Marinaro Mariarosaria , Saponaro Concetta , Escobar Marcillo David Israel , Loisi Donato , Sen Rajdip , Robitaille Alexis , Brancaccio Rosario N. , Cuenin Cyrille , McKay-Chopin Sandrine , Paradiso Angelo Virgilio , Liška Václav , Souček Pavel , Zito Francesco Alfredo , Hughes David J. , Tommasino Massimo , Gheit Tarik 
Published: November 2023

Abstract
Background
Although the role of viral agents, such as human papillomavirus (e.g. HPV16, HPV18) in colorectal cancer (CRC) has been previously investigated, results remain inconclusive.

Methods
To further evaluate the involvement of oncogenic HPV types in CRC, 40 frozen neoplastic and 40 adjacent colonic tissues collected from Italian patients were analyzed by Luminex-based assays that detect a broad spectrum of HPV types, i.e. Alpha (n = 21), Beta (n = 46) and Gamma HPVs (n = 52). In addition, 125 frozen CRC samples and 70 surrounding mucosal tissues were collected from Czech patients and analyzed by broad spectrum PCR protocols: (i) FAP59/64, (ii) FAPM1 and (iii) CUT combined with Next Generation Sequencing (NGS).

Results
Using Luminex-basedassays, DNA from HPV16 was detected in 5% (2/40) CRC tissues from Italian patients. One HPV16 DNA-positive CRC case was subsequently confirmed positive for E6*I mRNA. Cutaneous beta HPV types were detected in 10% (4/40) adjacent tissues only, namely HPV111 (n = 3) and HPV120 (n = 1), while gamma HPV168 (n = 1) and HPV199 (n = 1) types were detected in adjacent and in tumor tissues, respectively. The NGS analysis of the CRC Czech samples identified HPV sequences from mucosal alpha-3 (HPV89), alpha-7 (HPV18, 39, 68 and 70) and alpha-10 species (HPV11), as well as cutaneous beta-1 (HPV20, 24, 93, 98, 105,124) beta-2 (HPV23), beta-3 (HPV49) and gamma-1 species (HPV205).

Conclusions
Our findings indicate that HPV types belonging to the mucosal alpha, and the ‘cutaneous’ beta and gamma genera can be detected in the colonic mucosal samples with a low prevalence rate and a low number of HPV reads by Luminex and NGS, respectively. However, additional studies are required to corroborate these findings.
Single-session intervention on growth mindset on negative emotions for university student mental health (U-SIGMA): a protocol of two-armed randomized controlled trial
Authors: Zhu Shimin , Hu Yuxi , Qi Di , Qin Nan , Chi Xinli , Luo Jiawen , Wu Jie , Huang Hua , Wu Qiaobing , Yu Lu , Ni Shiguang , Hamilton Kyra , Tse Samson 
Published: November 2023

Abstract
Background
The university years are a developmentally crucial phase and a peak period for the onset of mental disorders. The beliefs about the changeability of negative emotion may play an important role in help-seeking. The brief digital growth mindset intervention is potentially scalable and acceptable to enhance adaptive coping and help-seeking for mental health needs in university students. We adapted the Single-session Intervention on Growth Mindset for adolescents (SIGMA) to be applied in university students (U-SIGMA). This protocol introduces a two-armed waitlist randomized controlled trial study to examine the effectiveness and acceptability of U-SIGMA in promoting help-seeking among university students in the Greater Bay Area.

Methods
University students (N = 250, ages 18–25) from universities in the Greater Bay Area will be randomized to either the brief digital growth mindset intervention group or the waitlist control group. Participants will report on the mindsets of negative emotions, perceived control over anxiety, attitude toward help-seeking, physical activity, hopelessness, psychological well-being, depression, anxiety, and perceived stress at baseline and the 2-week and 8-week follow-ups through web-based surveys. A 30-min digital intervention will be implemented in the intervention group, with a pre- and post-intervention survey collecting intervention feedback, while the control group will receive the link for intervention after 8 weeks.

Discussion
This protocol introduces the implementation plan of U-SIMGA in multi-cities of the Greater Bay Area. The findings are expected to help provide pioneer evidence for the effectiveness and acceptability of the brief digital intervention for university students in the Chinese context and beyond and contribute to the development of accessible and effective prevention and early intervention for university students’ mental health.

Trial registration
HKU Clinical Trials Registry: HKUCTR-3012; Registered 14 April 2023. http://www.hkuctr.com/Study/Show/7a3ffbc0e03f4d1eac0525450fc5187e.
Blood biomarkers for estimating energy intake in Japanese male collegiate athletes: a pilot study
Authors: Kurosaka Yuka , Nagasawa Takaaki , Minato Kumiko , Hasegawa-Tanaka Tomomi , Naito Hisashi , Wakui Sawako , Machida Shuichi 
Published: November 2023

Abstract
Background
Athletes should be informed of their required energy intake in preparation for sports competitions. However, the environment in which dietary surveys can be conducted to determine the required energy intake for sports competitions is limited, and such survey will require a substantial amount of time and effort from athletes and dietitians. If certain biomarkers for estimating the energy intake can be identified, they may compensate for the shortcomings of these dietary surveys. We aimed to identify the blood biomarkers to estimate the energy intake/basal metabolic rate ratio of male athletes.

Methods
Twenty-six male athletes from a university physical education department were included and underwent measurements of height, weight, and body composition, as well as blood sampling. The dietary assessment included a 3-day dietary recall and collection of meal photographs. The basal metabolic rate was estimated using the lean body mass, while the daily energy intake/basal metabolic rate ratio was used as an index to determine the energy intake. From the 36 selected blood biomarkers, we identified the independent biomarkers for inclusion in the multiple regression analysis by assessing for pairwise correlations and multicollinearity. A formula for estimating the energy intake/basal metabolic rate was then developed using the stepwise method. A p-value of < 0.05 was considered significant.

Results
Overall, 18 of the 36 blood biomarkers were selected, and multiple regression analysis revealed that triiodothyronine, white blood cell count, and triglyceride level were significant factors that can be used to estimate the energy intake/basal metabolic rate, accounting for 60.4% of the variance. No systematic errors were observed in the estimated values, calculated using the estimation formula and dietary assessment results.

Conclusions
A combination of free triiodothyronine level, white blood cell count, and triglyceride level can be used for estimating the energy intake/basal metabolic rate of male athletes, thus compensating for the shortcomings of dietary surveys.
Pilot study: is there an influence of lower limb positioning during magnetic resonance imaging on muscle cross section shape assessment in the thigh?
Authors: Oberhofer Katja , Blum Matthias , Achermann Basil , Lorenzetti Silvio R. 
Published: November 2023

AbstractPositioning in an MRI can influence quantitative measures of the muscle. The goal of this pilot study was to assess the influence of different levels of knee elevation during MRI on the predicted cross-sectional muscle shape in the thigh. Data were acquired in three healthy male participants (age: 29.3 ± 5.1y, height: 181.3 ± 6.4cm, weight: 85.1 ± 3.7kg). For each participant, three MRI scans were taken by a trained radiographer with low, moderate and high knee elevation. The shape of the anatomical cross-sectional areas of the hamstrings and quadriceps in three leg positionings were compared by fitting ellipsoidal functions to the segmented MRI data and calculating the so-called J index for every image slice using the Python scripting language. Different levels of knee elevation resulted in apparent changes in J index for all muscles except vastus medialis. Thereby, the changes were overall more pronounced in the hamstrings compared to the quadriceps. Particularly, by elevating the knee from 8 to 15 degree, the percentage changes in J index were between 7.2 and 13.6% for the hamstrings and between 0.5 and 3.3% for the quadriceps, respectively. For assessing the musculoskeletal properties by means of MRI, a standardized positioning of the leg is required and the knee joint angle should be controlled.
A comparative study of clustering methods on gene expression data for lung cancer prognosis
Authors: Zhang Jason Z. , Wang Chi 
Published: November 2023

AbstractLung cancer subtyping based on gene expression data is important for identifying patient subgroups with differing survival prognosis to facilitate customized treatment strategies for each subtype of patients. Unsupervised clustering methods are the traditional approach for clustering patients into subtypes. However, since those methods cluster patients based only on gene expression data, the resulting clusters may not always be relevant to the survival outcome of interest. In recent years, semi-supervised and supervised methods have been proposed, which leverage the survival outcome data to identify clusters more relevant to survival prognosis. This paper aims to compare the performance of different clustering methods for identifying clinically prognostic lung cancer subtypes based on two lung adenocarcinoma datasets. For each method, we clustered patients into two clusters and assessed the difference in patient survival time between clusters. Unsupervised methods were found to have large logrank p-values and no significant results in most cases. Semi-supervised and supervised methods had improved performance over unsupervised methods and very significant p-values. These results indicate that unsupervised methods are not capable of identifying clusters with significant differences in survival prognosis in most cases, while supervised and semi-supervised methods can better cluster patients into clinically useful subtypes.
Tazemetostat decreases β-catenin and CD13 protein expression in HEPG-2 and Hepatitis B virus-transfected HEPG-2 with decreased cell viability
Authors: Amin Mohamed N. , El-Far Yousra M. , El-Mowafy Mohammed , Elgaml Abdelaziz 
Published: November 2023

AbstractHepatocellular carcinoma (HCC) is one of the global health concerns. Hepatitis B virus (HBV) is one of the major causes of HCC. Poor clinical outcome of HCC patients is attributed to a small population of cancer cells known as cancer stem cells (CSCs). In this work, we studied the effect of inhibiting the enhancer of zeste homologue 2 (EZH2), a histone methyltransferase known to be overexpressed in CSCs, using tazemetostat (Taz). The effect of Taz was assessed in the HCC cell line (HEPG2) and Hepatitis B virus-transfected HEPG2 (HBV/HEPG2) cells. MTT assay showed a significant decrease in HEPG2 cells viability after 48 h treatment with either 0.5, 1, 4 or 6 μM Taz. HEPG2 and HBV/HEPG2 cells were incubated with either 0.5 or 1 μM Taz for 48 h, and then, the cells and supernatants were collected for protein expression analysis of EZH2, CD13, epithelial cell adhesion molecule (EpCAM) and β-catenin using enzyme-linked immunosorbent assay (ELISA). Taz showed a significant dose-dependent inhibition of EZH2, CD13 and β-catenin in HEPG2 and HBV/HEPG2 cells. Also, EpCAM protein levels were significantly decreased in HBV/HEPG2 but not in HEPG2 cell line alone. Our results indicate that Taz inhibition of EZH2 leads to downregulation of β-catenin signaling and eventually decreased expression of CD13 and EpCAM, which are characteristic for CSCs. The present study suggests that Taz could be a promising treatment for HCC including HBV-induced HCC that might be used in combination with radio/chemotherapy to target CSCs and prevent tumor relapse.