bluuebunny/crossref_metadata_2025_split huggingface dataset:
O-GlcNAcylation homeostasis controlled by calcium influx channels regulates multiple myeloma dissemination
Authors: Samart Parinya , Luanpitpong Sudjit , Rojanasakul Yon , Issaragrisil Surapol 
Published: March 2021

Abstract
Background
Multiple myeloma (MM) cell motility is a critical step during MM dissemination throughout the body, but how it is regulated remains largely unknown. As hypercalcemia is an important clinical feature of MM, high calcium (Ca2+) and altered Ca2+ signaling could be a key contributing factor to the pathological process.

Methods
Bioinformatics analyses were employed to assess the clinical significance of Ca2+ influx channels in clinical specimens of smoldering and symptomatic MM. Functional and regulatory roles of influx channels and downstream signaling in MM cell migration and invasion were conducted and experimental MM dissemination was examined in a xenograft mouse model using in vivo live imaging and engraftment analysis.

Results
Inhibition of TRPM7, ORAI1, and STIM1 influx channels, which are highly expressed in MM patients, and subsequent blockage of Ca2+ influx by CRISPR/Cas9 and small molecule inhibitors, effectively inhibit MM cell migration and invasion, and attenuate the experimental MM dissemination. Mechanistic studies reveal a nutrient sensor O-GlcNAcylation as a downstream regulator of Ca2+ influx that specifically targets cell adhesion molecules. Hyper-O-GlcNAcylation following the inhibition of Ca2+ influx channels induces integrin α4 and integrin β7 downregulation via ubiquitin-proteasomal degradation and represses the aggressive MM phenotype.

Conclusions
Our findings unveil a novel regulatory mechanism of MM cell motility via Ca2+ influx/O-GlcNAcylation axis that directly targets integrin α4 and integrin β7, providing mechanistic insights into the pathogenesis and progression of MM and demonstrating potential predictive biomarkers and therapeutic targets for advanced MM.
Early intervention of atopic dermatitis as a preventive strategy for progression of food allergy
Authors: Sweeney Alyssa , Sampath Vanitha , Nadeau Kari C. 
Published: March 2021

Abstract
Background
Atopic diseases, such as atopic dermatitis (AD) and food allergy (FA), have increased in prevalence in industrialized countries during the past few decades and pose a significant health burden. They appear to have a common underlying mechanism and a natural disease progression. AD is generally the first atopic disease to manifest followed by other atopic diseases, such as FA, allergic rhinitis, or allergic asthma suggesting that they are likely different manifestations of the same disease.

Body
Evidence suggests that allergic sensitization occurs through an impaired skin barrier, while consumption of these foods at an early age may actually result in tolerance. This has been termed the Dual-Allergen-Exposure hypothesis. Loss of barrier integrity has been hypothesized to enable penetration of allergens, pollutants, and microbes and initiation of an inflammatory immune cascade of events leading to sensitization. The immune dysfunction is thought to further exacerbate the impaired skin barrier to form a vicious cycle. There is much interest in preventing or protecting the skin barrier from developing a proinflammatory atopic state, which may potentially lead to the development of AD and subsequently, FA.

Conclusion
Research on preventing or treating skin barrier dysfunction is ongoing. A number of studies have evaluated the efficacy of emollients in preventing AD and FA with mixed results. Studies have differed in the study design, population characteristics, emollients type, and frequency, duration, and area of application. Emollient type has varied widely from oils, creams, petrolatum-based lotions, and trilipid creams. Current research is directed towards the use of trilipid emollients that are similar to the skin’s natural lipid composition with a 3:1:1 ratio of ceramides, cholesterol and free fatty acids and a pH that is similar to that of skin to determine their effectiveness for skin barrier repair and prevention of AD and FA.
Secreted factors from dental pulp stem cells improve Sjögren’s syndrome via regulatory T cell-mediated immunosuppression
Authors: Matsumura-Kawashima Mayu , Ogata Kenichi , Moriyama Masafumi , Murakami Yuka , Kawado Tatsuya , Nakamura Seiji 
Published: March 2021

Abstract
Background
Sjögren’s syndrome (SS) is a chronic autoimmune disease primarily characterized by inflammation in the salivary and lacrimal glands. Activated T cells contribute to disease pathogenesis by producing proinflammatory cytokines, which leads to a positive feedback loop establishment. The study aimed to evaluate the effects of secreted factors derived from dental pulp stem cells (DPSCs) or bone marrow mesenchymal stem cells (BMMSCs) on hyposalivation in SS and to investigate the mechanism involved.

Methods
Eighty percent confluent stem cells were replenished with serum-free Dulbecco’s modified Eagle’s medium and incubated for 48 h; following which, conditioned media from DPSCs (DPSC-CM) and BMMSCs (BMMSC-CM) were collected. Cytokine array analysis was performed to assess the types of cytokines present in the media. Flow cytometric analysis was performed to evaluate the number of activated T cells cultured in DPSC-CM or BMMSC-CM. Subsequently, DPSC-CM or BMMSC-CM was administered to an SS mouse model. The mice were categorized into the following groups (n = 6 each): non-treatment, Dulbecco’s modified Eagle’s medium (−), BMMSC-CM, and DPSC-CM. Histological analysis of the salivary glands was performed. The gene and protein expression levels of cytokines associated with T helper subsets in the submandibular glands (SMGs) were evaluated.

Results
DPSC-CM contained more secreted factors with tissue-regenerating mechanisms, such as cell proliferation, anti-inflammatory effects, and immunomodulatory effects. DPSC-CM was more effective in suppressing the activated T cells than other groups in the flow cytometric analysis. The stimulated salivary flow rate increased in SS mice with DPSC-CM compared with that in the other groups. In addition, the number of inflammation sites in SMGs of the mice administered with DPSC-CM was lower than that in the other groups. The expression levels of interleukin (Il)-10 and transforming growth factor-β1 were upregulated in the DPSC-CM group, whereas those of Il-4 and Il-17a were downregulated. The DPSC-CM-administered group presented with a significantly increased percentage of regulatory T (Treg) cells and a significantly decreased percentage of type 17 Th (Th17) cells compared with the other groups.

Conclusions
These results indicated that DPSC-CM ameliorated SS by promoting Treg cell differentiation and inhibiting Th17 cell differentiation in the mouse spleen.
Conditionally optimal classification based on CFAR and invariance property for blind receivers
Authors: Naderpour Masoud , Bizaki Hossein Khaleghi 
Published: March 2021

AbstractThis paper proposes a new approach for finding the conditionally optimal solution (the classifier with minimum error probability) for the classification problem where the observations are from the multivariate normal distribution. The optimal Bayes classifier does not exist when the covariance matrix is unknown for this problem. However, this paper proposes a classifier based on the constant false alarm rate (CFAR) and invariance property. The proposed classifier is optimal conditionally as it has the minimum error probability in a subset of solutions. This approach has an analogy to hypothesis testing problems where uniformly most powerful invariant (UMPI) and uniformly most powerful unbiased (UMPU) detectors are used instead of the non-existing optimal UMP detector. Furthermore, this paper investigates using the proposed classifier for modulation classification as an application in signal processing.
Are mental disorders related to disbelief in free will? A systematic review
Authors: Moreira-de-Oliveira Maria E. , de Menezes Gabriela B. , dos Santos-Ribeiro Samara , Laurito Luana D. , Ribeiro Ana P. , Carter Adrian , Fontenelle Leonardo F. 
Published: March 2021

Abstract
Background
The nature and existence of free will have been debated for centuries. Since some psychiatric disorders are known to interfere with one’s ability to control their actions and thoughts (e.g., schizophrenia), the investigation of the psychiatric facet of free will beliefs seems to be relevant. In this systematic review, we were interested in clarifying if and how having a mental disorder affects individuals’ beliefs in free will by comparing psychiatric vs. non-psychiatric samples.

Methods
A systematic search of MEDLINE, Web of Science, EMBASE, and PsycINFO databases was performed between 04 and 09 November 2020. The search strategy included “free will” and related constructs and terms related to DSM-5 mental disorders characterized by psychotic, compulsive, avoidant, or impulsive symptoms. Eligible designs of studies included case-control and cohort studies. Study selection took place in committee meetings consisting of six researchers. Quality assessment of the selected studies was performed through the Joanna Briggs Institute Appraisal Checklist for Case Control Studies.

Results
After removing duplicates, a total of 12,218 titles/abstracts were screened. Inclusion and exclusion criteria were followed, and three articles were eventually selected.

Conclusions
It is not possible to provide unequivocal confirmation that having a mental disorder can or cannot affect someone’s belief in free will. Studies with different mental disorders should be conducted in this field.

Systematic review registration
PROSPERO CRD42018109468.
Associations between habitual diet, metabolic disease, and the gut microbiota using latent Dirichlet allocation
Authors: Breuninger Taylor A. , Wawro Nina , Breuninger Jakob , Reitmeier Sandra , Clavel Thomas , Six-Merker Julia , Pestoni Giulia , Rohrmann Sabine , Rathmann Wolfgang , Peters Annette , Grallert Harald , Meisinger Christa , Haller Dirk , Linseisen Jakob 
Published: March 2021

AbstractBackgroundThe gut microbiome impacts human health through various mechanisms and is involved in the development of a range of non-communicable diseases. Diet is a well-known factor influencing microbe-host interaction in health and disease. However, very few findings are based on large-scale analysis using population-based studies. Our aim was to investigate the cross-sectional relationship between habitual dietary intake and gut microbiota structure in the Cooperative Health Research in the Region of Augsburg (KORA) FF4 study.ResultsFecal microbiota was analyzed using 16S rRNA gene amplicon sequencing. Latent Dirichlet allocation (LDA) was applied to samples from 1992 participants to identify 20 microbial subgroups within the study population. Each participant’s gut microbiota was subsequently described by a unique composition of these 20 subgroups. Associations between habitual dietary intake, assessed via repeated 24-h food lists and a Food Frequency Questionnaire, and the 20 subgroups, as well as between prevalence of metabolic diseases/risk factors and the subgroups, were assessed with multivariate-adjusted Dirichlet regression models. After adjustment for multiple testing, eight of 20 microbial subgroups were significantly associated with habitual diet, while nine of 20 microbial subgroups were associated with the prevalence of one or more metabolic diseases/risk factors. Subgroups 5 (Faecalibacterium,Lachnospiracea incertae sedis,Gemmiger,Roseburia) and 14 (Coprococcus,Bacteroides,Faecalibacterium,Ruminococcus) were particularly strongly associated with diet. For example, participants with a high probability for subgroup 5 were characterized by a higher Alternate Healthy Eating Index and Mediterranean Diet Score and a higher intake of food items such as fruits, vegetables, legumes, and whole grains, while participants with prevalent type 2 diabetes mellitus were characterized by a lower probability for subgroup 5.ConclusionsThe associations between habitual diet, metabolic diseases, and microbial subgroups identified in this analysis not only expand upon current knowledge of diet-microbiota-disease relationships, but also indicate the possibility of certain microbial groups to be modulated by dietary intervention, with the potential of impacting human health. Additionally, LDA appears to be a powerful tool for interpreting latent structures of the human gut microbiota. However, the subgroups and associations observed in this analysis need to be replicated in further studies.
Expression of an alternatively spliced variant of SORL1 in neuronal dendrites is decreased in patients with Alzheimer’s disease
Authors: Monti Giulia , Kjolby Mads , Jensen Anne Mette G. , Allen Mariet , Reiche Juliane , Møller Peter L. , Comaposada-Baró Raquel , Zolkowski Bartlomiej E. , Vieira Cármen , Jørgensen Margarita Melnikova , Holm Ida E. , Valdmanis Paul N. , Wellner Niels , Vægter Christian B. , Lincoln Sarah J. , Nykjær Anders , Ertekin-Taner Nilüfer , Young Jessica E. , Nyegaard Mette , Andersen Olav M. 
Published: March 2021

AbstractSORL1 is strongly associated with both sporadic and familial forms of Alzheimer’s disease (AD), but a lack of information about alternatively spliced transcripts currently limits our understanding of the role of SORL1 in AD. Here, we describe a SORL1 transcript (SORL1-38b) characterized by inclusion of a novel exon (E38b) that encodes a truncated protein. We identified E38b-containing transcripts in several brain regions, with the highest expression in the cerebellum and showed that SORL1-38b is largely located in neuronal dendrites, which is in contrast to the somatic distribution of transcripts encoding the full-length SORLA protein (SORL1-fl). SORL1-38b transcript levels were significantly reduced in AD cerebellum in three independent cohorts of postmortem brains, whereas no changes were observed for SORL1-fl. A trend of lower 38b transcript level in cerebellum was found for individuals carrying the risk variant at rs2282649 (known as SNP24), although not reaching statistical significance. These findings suggest synaptic functions for SORL1-38b in the brain, uncovering novel aspects of SORL1 that can be further explored in AD research.
Application of diffusion kurtosis tensor MR imaging in characterization of renal cell carcinomas with different pathological types and grades
Authors: Zhu Jie , Luo Xiaojie , Gao Jiayin , Li Saying , Li Chunmei , Chen Min 
Published: March 2021

Abstract
Background
To probe the feasibility and reproducibility of diffusion kurtosis tensor imaging (DKTI) in renal cell carcinoma (RCC) and to apply DKTI in distinguishing the subtypes of RCC and the grades of clear cell RCC (CCRCC).

Methods
Thirty-eight patients with pathologically confirmed RCCs [CCRCC for 30 tumors, papillary RCC (PRCC) for 5 tumors and chromophobic RCC (CRCC) for 3 tumors] were involved in the study. Diffusion kurtosis tensor MR imaging were performed with 3 b-values (0, 500, 1000s/mm2) and 30 diffusion directions. The mean kurtosis (MK), axial kurtosis (Ka), radial kurtosis (Kr) values and mean diffusity (MD) for RCC and contralateral normal parenchyma were acquired. The inter-observer agreements of all DKTI metrics of contralateral renal cortex and medulla were evaluated using Bland-Altman plots. Statistical comparisons with DKTI metrics of 3 RCC subtypes and between low-grade (Furman grade I ~ II, 22 cases) and high-grade (Furman grade III ~ IV, 8 cases) CCRCC were performed with ANOVA test and Student t test separately. Receiver operating characteristic (ROC) curve analyses were used to compare the diagnostic efficacy of DKTI metrics for predicting nuclear grades of CCRCC. Correlations between DKTI metrics and nuclear grades were also evaluated with Spearman correlation analysis.

Results
Inter-observer measurements for each metric showed great reproducibility with excellent ICCs ranging from 0.81 to 0.87. There were significant differences between the DKTI metrics of RCCs and contralateral renal parenchyma, also among the subtypes of RCC. MK and Ka values of CRCC were significantly higher than those of CCRCC and PRCC. Statistical difference of the MK, Ka, Kr and MD values were also obtained between CCRCC with high- and low-grades. MK values were more effective for distinguishing between low- and high- grade CCRCC (area under the ROC curve: 0.949). A threshold value of 0.851 permitted distinction with high sensitivity (90.9%) and specificity (87.5%).

Conclusion
Our preliminary results suggest a possible role of DKTI in differentiating CRCC from CCRCC and PRCC. MK, the principle DKTI metric might be a surrogate biomarker to predict nuclear grades of CCRCC.

Trial registration
ChiCTC, ChiCTR-DOD-17010833, Registered 10 March, 2017, retrospectively registered, http://www.chictr.org.cn/showproj.aspx?proj=17559.
Using Field Based Data to Model Sprint Track Cycling Performance
Authors: Ferguson Hamish A. , Harnish Chris , Chase J. Geoffrey 
Published: March 2021

AbstractCycling performance models are used to study rider and sport characteristics to better understand performance determinants and optimise competition outcomes. Performance requirements cover the demands of competition a cyclist may encounter, whilst rider attributes are physical, technical and psychological characteristics contributing to performance. Several current models of endurance-cycling enhance understanding of performance in road cycling and track endurance, relying on a supply and demand perspective. However, they have yet to be developed for sprint-cycling, with current athlete preparation, instead relying on measures of peak-power, speed and strength to assess performance and guide training. Peak-power models do not adequately explain the demands of actual competition in events over 15-60 s, let alone, in World-Championship sprint cycling events comprising several rounds to medal finals. Whilst there are no descriptive studies of track-sprint cycling events, we present data from physiological interventions using track cycling and repeated sprint exercise research in multiple sports, to elucidate the demands of performance requiring several maximal sprints over a competition. This review will show physiological and power meter data, illustrating the role of all energy pathways in sprint performance. This understanding highlights the need to focus on the capacity required for a given race and over an event, and therefore the recovery needed for each subsequent race, within and between races, and how optimal pacing can be used to enhance performance. We propose a shift in sprint-cyclist preparation away from training just for peak power, to a more comprehensive model of the actual event demands.
On the enzymes’ actions of entomopathogenic fungi against certain indigenous and invasive insect pests
Authors: Moharram A. M. , Abdel-Galil F. A. , Hafez W. M. M. 
Published: March 2021

Abstract
Background
Pathogenicity of entomopathogenic fungi (EPF) depends mainly on their ability to produce efficient enzymes, which degrade insect’s integument and other cellular components. Lipases are the first enzymes secreted by these fungi, then proteases, phospholipases, and chitinases.

Results
Twenty-six fungal strains, isolated from the aphids, Aphis sp., Linnaeus (Homoptera, Aphididae), the tomato leaf minor, Liriomyza trifolii, Burgess (Diptera, Agromyzidae) (indigenous insects), the red palm weevil, Rhynchophorus ferrugineus, Olivier (Coleoptera, Curculionidae), and the peach fruit fly, Bactrocera zonata, Saunders (Diptera, Tephritidae) (invasive insects) were tested for their enzymatic activities. Results showed that the majority of these strains were able to produce lipolytic enzymes with the most active being Aspergillus niger, Botryotrichum atrogriseum, Cochliobolus spicifer, Fusarium chlamydosporum, and F. proliferatum. Phospholipase was successfully produced by 73.1% of the tested strains among which Aspergillus flavus, A. niger, Mucor racemosus, Pochonia chlamydosporia var. catenulata, and Scopulariopsis brevicaulis were the highest producers. Proteolytic enzymes were detected in cultures of all the fungal strains except Aspergillus chevalieri and M. racemosus. The best proteolytic strain was S. brevicaulis followed by A. flavus, A. sydowii, and F. semitectum. The chitinolytic ability of the fungal strains was generally weak and the relatively active species belonged to A. flavus, A. niger, B. atrogriseum, F. chlamydosporum, F. solani, S. brevicaulis, and Nigrospora oryzae. Quantitative determination of chitinase revealed that the enzyme concentration ranged from 3.478 to 6.44 IU/ml.

Conclusion
Most of the isolated fungi had enzymatic activities, but A. niger, F. semitectum, F. solani, F. chlamydosporum, P. chlamydosporia var. catenulata, and S. brevicaulis, were the most active ones.
Frequency of peri-ictal apnea and cardiac arrhythmias in epileptic seizures
Authors: Yousif Rady , Abdulghani M. Ossama , Gaber A. , El Khayat Naglaa , Abo Elnaga Y. A. , Wahid El Din Mona Mokhtar 
Published: March 2021

Abstract
Background
Available data from witnessed and monitored sudden unexpected death in epilepsy (SUDEP) cases postulate that ictal central apnea (ICA) and ictal arrhythmias are the main causes of SUDEP. ICA is a frequent semiological feature of focal epilepsy and occasionally the only clinical manifestation of focal seizures. The aim of this study was to assess the frequency of ICA and cardiac arrhythmias in epileptic patients and to study the risk factors and predictors of their occurrence.

Methods
Fifty patients diagnosed with epilepsy were recruited in this study. All participants underwent prolonged surface video electroencephalography (VEEG) study using the 10-20 international electrode system with concomitant polysomnography including electrocardiography (ECG), heart rate monitoring, and peripheral capillary oxygen saturation (SpO2) using pulse oximetry. Also inductance plethysmography was used to record chest and abdominal excursions.

Results
Complete datasets were available in 50 patients and 112 seizures were recorded. ICA occurred exclusively in focal epilepsy (P <0.001). Temporal lobe epilepsy was associated with higher occurrence of ICA in comparison to extratemporal epilepsy (P <0.001). In addition, seizures lateralized to the left hemisphere were associated with higher occurrence of ICA (P <0.001). On the other side, tachycardia was found to be more associated with temporal lobe epilepsy and left hemispheric seizure onset (P <0.001).

Conclusion
ICA occurred exclusively in focal seizures and tachycardia magnitude was more with focal seizures, and both had higher percentage in temporal lobe epilepsy in comparison to other types and in seizures with left hemispheric onset.