bluuebunny/crossref_metadata_2025 huggingface dataset:
Genome-Wide Association Study of Muscle Glycogen in Jingxing Yellow Chicken
Authors: Liu Xiaojing , Liu Lu , Wang Jie , Cui Huanxian , Chu Huanhuan , Bi Huijuan , Zhao Guiping , Wen Jie
Published: May 2020

Glucose metabolism plays an important role in many normal and pathological physiological processes in the body. The breakdown and synthesis of muscle glycogen provides ATP for muscle activities. A genome-wide association study for muscle glycogen was performed in 474 Jingxing yellow chickens to identify significant single nucleotide polymorphisms (SNPs) and insertions and deletions (INDELs) involved in muscle glycogen metabolism. A total of nine SNPs (p < 1/699341) and three INDELs (p < 1/755733) reached a significant level of potential association. The following results were obtained through a series of analyses, including additive effects and gene function annotation. Two significant SNPs were found in introns 12 and 13 of copine 4 (CPNE4) on chromosome 2. The wild-type and mutant individuals had significant differences in glycogen metabolism at two loci (p < 0.01 for both). Individuals carrying two mutations had increased muscle glycogen content. According to the gene annotation of chromosome 11, there is a significant INDEL in intron 6 of naked cuticle homolog 1 (NKD1). After the INDEL mutation, the glycogen content increased significantly. There was a significant difference between wild-type and mutant individuals (p < 0.01). These mutations likely affecting two genes (CPNE4 and NKD1) may affect glycogen storage in a pleiotropic manner. Gene annotation indicates that CPNE4 and NKD1 may affect the process of glucose metabolism. Our findings contribute to understanding the genetic regulation of muscle glycogen metabolism and provide theoretical support.
Ancestry Prediction Comparisons of Different AISNPs for Five Continental Populations and Population Structure Dissection of the Xinjiang Hui Group via a Self-Developed Panel
Authors: Jin Xiao-Ye , Guo Yu-Xin , Chen Chong , Cui Wei , Liu Yan-Fang , Tai Yun-Chun , Zhu Bo-Feng
Published: May 2020

Ancestry informative markers are genetic markers that show distinct genetic divergences among different populations. These markers can be utilized to discern population substructures and estimate the ancestral origins of unknown individuals. Previously, we developed a multiplex system of 30 ancestry informative single nucleotide polymorphism (AISNP) loci to facilitate ancestral inferences in different continental populations. In the current study, we first compared the ancestry resolutions of the 30 AISNPs and the other previously reported AISNP panels for African, European, East Asian, South Asian and American populations. Next, the genetic components of the Xinjiang Hui group were further explored in comparison to these continental populations based on the 30 AISNPs. Genetic divergence analyses of the 30 AISNPs in these five continental populations revealed that most of the AISNPs showed high genetic differentiations between these populations. Ancestry analysis comparisons of the 30 AISNPs and other published AISNPs revealed that these 30 AISNPs had comparable efficiency to other AISNP panels. Genetic relationship analyses among the studied Hui group and other continental populations demonstrated that the Hui group had close genetic affinities with East Asian populations and might share the genetic ancestries with East Asian populations. Overall, the 30 AISNPs can be used to predict the bio-geographical origins of different continental populations. Moreover, the obtained genetic data of 30 AISNPs in the Hui group can further enrich the extant reference data, which can be used as reference data for ancestry analyses of the Hui group.
Identification and Comparative Analysis of Long Non-Coding RNA in the Skeletal Muscle of Two Dezhou Donkey Strains
Authors: Shi Tianpei , Hu Wenping , Hou Haobin , Zhao Zhida , Shang Mingyu , Zhang Li
Published: May 2020

Long non-coding RNA (lncRNA) has been extensively studied in many livestock. However, compared with other livestock breeds, there is less research regarding donkey lncRNA function. It has been reported that lncRNA plays an important role in the timing control of development, aging, and death of livestock. Therefore, the study of donkey skeletal muscle lncRNA is of great significance for exploring donkey meat production performance. In this study, RNA-Seq was used to perform high-throughput sequencing of skeletal muscle (longissimus dorsi and gluteus) of two Dezhou donkey strains (SanFen and WuTou). The differentially expressed lncRNAs were screened between different strains and tissues. Then candidate genes for conjoint analysis were screened based on Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. Finally, the accuracy of the sequencing data was verified by real-time quantitative polymerase chain reaction (RT-qPCR). Herein, we identified 3869 novel lncRNAs and 73 differentially expressed lncRNAs. Through the comparison between groups, the specific expression of lncRNAs were found in different strains and muscle tissues. Importantly, we constructed the lncRNA-miRNA-mRNA interaction network and found three important candidate lncRNAs (MSTRG.9787.1, MSTRG.3144.1, and MSTRG.9886.1) and four candidate genes (ACTN1, CDON, FMOD, and BMPR1B). Analysis of the KEGG pathway indicates that the TGF-β signaling pathway plays a pivotal role in the growth and development of skeletal muscle in Dezhou donkey strains.
Association of Specific Comorbidities with Monosodium Urate Crystal Deposition in Urate-Lowering Therapy-Naive Gout Patients: A Cross-Sectional Dual-Energy Computed Tomography Study
Authors: Pascart Tristan , Ramon André , Ottaviani Sébastien , Legrand Julie , Ducoulombier Vincent , Houvenagel Eric , Norberciak Laurène , Richette Pascal , Becce Fabio , Ornetti Paul , Budzik Jean-François
Published: May 2020

(1) Background: To determine which factors are associated with the volume of monosodium urate (MSU) crystal deposition quantified by dual-energy computed tomography (DECT) in urate-lowering therapy (ULT)-naive gout patients. (2) Methods: In this multicenter cross-sectional study, DECT scans of knees and feet/ankles were prospectively obtained from ULT-naive gout patients. Demographic, clinical (including gout history and comorbidities), and biological data were collected, and their association with DECT MSU crystal volume was analyzed using bivariate and multivariate analyses. A second bivariate analysis was performed by splitting the dataset depending on an arbitrary threshold of DECT MSU volume (1 cm3). (3) Results: A total of 91 patients were included. In the bivariate analysis, age (p = 0.03), gout duration (p = 0.003), subcutaneous tophi (p = 0.004), hypertension (p = 0.02), diabetes mellitus (p = 0.05), and chronic heart failure (p = 0.03) were associated with the total DECT volume of MSU crystal deposition. In the multivariate analysis, factors associated with DECT MSU volumes ≥1 cm3 were gout duration (odds ratio (OR) for each 10-year increase 3.15 (1.60; 7.63)), diabetes mellitus (OR 4.75 (1.58; 15.63)), and chronic heart failure (OR 7.82 (2.29; 31.38)). (4) Conclusion: Specific comorbidities, particularly chronic heart failure and diabetes mellitus, are more strongly associated with increased MSU crystal deposition in knees and feet/ankles than gout duration, regardless of serum urate level.
What Determines Spontaneous Physical Activity in Patients with Parkinson’s Disease?
Authors: Gorzkowska Agnieszka , Cholewa Joanna , Małecki Andrzej , Klimkowicz-Mrowiec Aleksandra , Cholewa Jarosław
Published: May 2020

Physical activity (PA) is a factor that may have an influence on the symptoms of Parkinson’s disease (PD). The aim of this study was to identify the potential determinants of spontaneous PA in a PD patient group. A total of 134 PD patients aged 65.2 ± 9.2 years with a Hoehn–Yahr scale score ≤4 and a Mini Mental State Examination (MMSE) score ≥24 were examined. For the study’s purposes, the authors analyzed age, sex, education, history of PD, dopaminergic treatment, the severity of PD symptoms using Unified Parkinson’s Disease Rating Scale (UPDRS), and Hoehn–Yahr scale. Additionally, all participants were evaluated through a set of scales for specific neuropsychiatric symptoms including depression, anxiety, apathy, fatigue, and sleep disorders. A linear regression analysis was used with backward elimination. In the total explanatory model, for 12% of the variability in activity (R2 = 0.125; F(16.133) = 2.185; p < 0.01), the significant predictor was starting therapy with the dopamine agonist (DA) (β= 0.420; t= 4.068; p = 0.000), which was associated with a longer duration of moderate PA. In the total explanatory model, for more than 13% of the variance in time spent sitting (R2 = 0.135; F(16.130) = 2.267; p < 0.01), the significant predictors were secondary education and the results of the UPDRS. The patients with secondary and vocational education, those starting treatment with DA and those with a less severe degree of Parkinson’s symptoms (UPDRS), spent less time sitting in a day. It is possible to identify determinants of spontaneous PA. It may elucidate consequences in terms of influence on modifiable conditions of PA and the proper approach to patients with unmodifiable PA factors.
Predicting Total Knee Replacement from Symptomology and Radiographic Structural Change Using Artificial Neural Networks—Data from the Osteoarthritis Initiative (OAI)
Authors: Heisinger Stephan , Hitzl Wolfgang , Hobusch Gerhard M. , Windhager Reinhard , Cotofana Sebastian
Published: May 2020

The aim of the study was to longitudinally investigate symptomatic and structural factors prior to total knee replacement (TKR) surgery in order to identify influential factors that can predict a patient’s need for TKR surgery. In total, 165 participants (60% females; 64.5 ± 8.4 years; 29.7 ± 4.7 kg/m2) receiving a TKR in any of both knees within a four-year period were analyzed. Radiographic change, knee pain, knee function and quality of life were annually assessed prior to the TKR procedure. Self-learning artificial neural networks were applied to identify driving factors for the surgical procedure. Significant worsening of radiographic structural change was observed prior to TKR (p ≤ 0.0046), whereas knee symptoms (pain, function, quality of life) worsened significantly only in the year prior to the TKR procedure. By using our prediction model, we were able to predict correctly 80% of the classified individuals to undergo TKR surgery with a positive predictive value of 84% and a negative predictive value of 73%. Our prediction model offers the opportunity to assess a patient’s need for TKR surgery two years in advance based on easily available patient data and could therefore be used in a primary care setting.
Role of Reconstructive Microsurgery in Tubal Infertility in Young Women
Authors: Barac Sorin , Jiga Lucian Petru , Rata Andreea , Sas Ioan , Onofrei Roxana Ramona , Ionac Mihai
Published: May 2020

Aim: Here, we retrospectively analyzed the success rate of reconstructive microsurgery for tubal infertility (RMTI) as a “first-line” approach to achieving tubal reversal and pregnancy after tubal infertility. Patients and Methods: During 9 consecutive years (2005–2014), 96 patients diagnosed with obstructive tubal infertility underwent RMTI (tubal reversal, salpingostomy, and/or tubal implantation) in our centre. The outcomes are presented in terms of tubal reversal rate and pregnancy and correlated with age, level of tubal obstruction, and duration of tubal infertility. Results: The overall tubal reversal rate was 87.56% (84 patients). The 48-month cumulative pregnancy rate was 78.04% (64 patients), of which seven ectopic pregnancies occurred (8.53%). The reversibility rate for women under 35 yo was 90.47%, with a birth rate of 73.01%. The reconstruction at the infundibular segments favored higher ectopic pregnancy rates (four ectopic pregnancies for anastomosis at infundibular level—57.14%, two for ampullary level—28.57%, and one for replantation technique—14.28%), with a significant value for p < 0.05. Conclusions: In the context of IVF “industrialization”, reconstructive microsurgery for tubal infertility has become increasingly less favored. However, under available expertise and proper indication, RMTI can be successfully used to restore a woman’s ability to conceive naturally with a high postoperative pregnancy rate overall, especially in women under 35 yo.
Prediction of Motor Recovery in Patients with Basal Ganglia Hemorrhage Using Diffusion Tensor Imaging
Authors: Min Yu-Sun , Jang Kyung Eun , Park Eunhee , Kim Ae-Ryoung , Kang Min-Gu , Cheong Youn-Soo , Kim Ju-Hyun , Jung Seung-Hwan , Park Jaechan , Jung Tae-Du
Published: May 2020

Predicting prognosis in patients with basal ganglia hemorrhage is difficult. This study aimed to investigate the usefulness of diffusion tensor imaging in predicting motor outcome after basal ganglia hemorrhage. A total of 12 patients with putaminal hemorrhage were included in the study (aged 50 ± 12 years), 8 patients were male (aged 46 ± 11 years) and 4 were female (aged 59 ± 9 years). We performed diffusion tensor imaging and measured clinical outcome at baseline (pre) and 3 weeks (post1), 3 months (post2), and 6 months (post3) after the initial treatment. In the affected side of the brain, the mean fractional anisotropy (FA) value on pons was significantly higher in the good outcome group than that in the poor outcome group at pre (p = 0.004) and post3 (p = 0.025). Pearson correlation analysis showed that mean FA value at pre significantly correlated with the sum of the Brunnstrom motor recovery stage scores at post3 (R = 0.8, p = 0.002). Change in the FA ratio on diffusion tractography can predict motor recovery after hemorrhagic stroke.
The Effect of a Multicomponent Dual-Task Exercise on Cortical Thickness in Older Adults with Cognitive Decline: A Randomized Controlled Trial
Authors: Bae Seongryu , Harada Kenji , Lee Sangyoon , Harada Kazuhiro , Makino Keitaro , Chiba Ippei , Park Hyuntae , Shimada Hiroyuki
Published: May 2020

The aim of this study was to examine cortical thickness changes associated with a multicomponent exercise intervention combining physical exercise and cognitive training in older adults with cognitive decline. This study involved a secondary analysis of neuroimaging data from a randomized controlled trial with 280 older adults having cognitive decline who were randomly assigned to either a multicomponent exercise group (n = 140) that attended weekly 90-minute exercise and cognitive training sessions or a health education control group (n = 140). The cortical thickness and cognitive performance were assessed at the baseline and at trial completion (10 months). The cortical thickness in the frontal and temporal regions was determined using FreeSurfer software. Cognitive performance was evaluated using the Gerontology-Functional Assessment Tool (NCGG-FAT). The cortical thickness significantly increased in the middle temporal (p < 0.001) and temporal pole (p < 0.001) in the multicomponent exercise group compared with the control group. Cortical thickness changes were significantly associated with change in trail making test (TMT)-A, TMT-B, and story memory after a 10-month multicomponent exercise intervention. This study suggests that multicomponent exercise programs combining physical exercise and cognitive training have important implications for brain health, especially in providing protection from age-related cortical thinning.
Optimal Control Theory for Personalized Therapeutic Regimens in Oncology: Background, History, Challenges, and Opportunities
Authors: Jarrett Angela M. , Faghihi Danial , Hormuth David A. , Lima Ernesto A. B. F. , Virostko John , Biros George , Patt Debra , Yankeelov Thomas E.
Published: May 2020

Optimal control theory is branch of mathematics that aims to optimize a solution to a dynamical system. While the concept of using optimal control theory to improve treatment regimens in oncology is not novel, many of the early applications of this mathematical technique were not designed to work with routinely available data or produce results that can eventually be translated to the clinical setting. The purpose of this review is to discuss clinically relevant considerations for formulating and solving optimal control problems for treating cancer patients. Our review focuses on two of the most widely used cancer treatments, radiation therapy and systemic therapy, as they naturally lend themselves to optimal control theory as a means to personalize therapeutic plans in a rigorous fashion. To provide context for optimal control theory to address either of these two modalities, we first discuss the major limitations and difficulties oncologists face when considering alternate regimens for their patients. We then provide a brief introduction to optimal control theory before formulating the optimal control problem in the context of radiation and systemic therapy. We also summarize examples from the literature that illustrate these concepts. Finally, we present both challenges and opportunities for dramatically improving patient outcomes via the integration of clinically relevant, patient-specific, mathematical models and optimal control theory.
Clinical Characteristics and Disability Progression of Early- and Late-Onset Multiple Sclerosis Compared to Adult-Onset Multiple Sclerosis
Authors: Mirmosayyeb Omid , Brand Serge , Barzegar Mahdi , Afshari-Safavi Alireza , Nehzat Nasim , Shaygannejad Vahid , Sadeghi Bahmani Dena
Published: May 2020

Background: Compared to the adult onset of multiple sclerosis (AOMS), both early-onset (EOMS) and late-onset (LOMS) are much less frequent, but are often under- or misdiagnosed. The aims of the present study were: 1. To compare demographic and clinical features of individuals with EOMS, AOMS and LOMS, and 2. To identify predictors for disability progression from relapsing remitting MS (RRMS) to secondary progressive MS (SPMS). Method: Data were taken from the Isfahan Hakim MS database. Cases were classified as EOMS (MS onset ≤ 18 years), LOMS (MS onset >50 years) and AOMS (MS >18 and ≤ 50 years). Patients’ demographic and clinical (initial symptoms; course of disease; disease patterns from MRI; disease progress) information were gathered and assessed. Kaplan–Meier and Cox proportional hazard regressions were conducted to determine differences between the three groups in the time lapse in conversion from relapsing remitting MS to secondary progressive MS. Results: A total of 2627 MS cases were assessed; of these 127 were EOMS, 84 LOMS and 2416 AOMS. The mean age of those with EOMS was 14.5 years; key symptoms were visual impairments, brain stem dysfunction, sensory disturbances and motor dysfunctions. On average, 24.6 years after disease onset, 14.2% with relapsing remitting MS (RRMS) were diagnosed with secondary progressive MS (SPMS). The key predictor variable was a higher Expanded Disability Status Scale (EDSS) score at disease onset. Compared to individuals with AOMS and LOMS, those with EOMS more often had one or two relapses in the first two years, and more often gadolinium-enhancing brain lesions. For individuals with AOMS, mean age was 29.4 years; key symptoms were sensory disturbances, motor dysfunctions and visual impairments. On average, 20.5 years after disease onset, 15.6% with RRMS progressed to SPMS. The key predictors at disease onset were: a higher EDSS score, younger age, a shorter inter-attack interval and spinal lesions. Compared to individuals with EOMS and LOMS, individuals with AOMS more often had either no or three and more relapses in the first two years. For individuals with LOMS, mean age was 53.8 years; key symptoms were motor dysfunctions, sensory disturbances and visual impairments. On average, 14 years after disease onset, 25.3% with RRMS switched to an SPMS. The key predictors at disease onset were: occurrence of spinal lesions and spinal gadolinium-enhancement. Compared to individuals with EOMS and AOMS, individuals with LOMS more often had no relapses in the first two years, and higher EDSS scores at disease onset and at follow-up. Conclusion: Among a large sample of MS sufferers, cases with early onset and late onset are observable. Individuals with early, adult and late onset MS each display distinct features which should be taken in consideration in their treatment.
Endothelin-1 Serum Concentration is Lower in Children and Adolescents with High Myopia, a Preliminary Study
Authors: Powierza Katarzyna , Żelazowska-Rutkowska Beata , Sawicka-Powierza Jolanta , Mikołuć Bożena , Urban Beata , Zaremba Wojciech , Cylwik Bogdan , Bakunowicz-Łazarczyk Alina
Published: May 2020

The aim of this study is to evaluate the levels of enothelin-1 (ET-1) in children and adolescents with high myopia and its association with the axial length of the eye and the presence of myopic retinal degeneration. The cross-sectional study was carried out in 57 patients with high myopia and 29 control subjects. Serum concentrations of ET-1 were measured using enzyme-linked immunosorbent assay (ELISA) kit. A significantly lower concentration of ET-1 in highly myopic patients compared to controls was found (1.47 (0.91; 1.87) vs. 1.94 (1.1; 2.69) pg/mL, p = 0.005). In patients with high myopia, a weak negative correlation between ET-1 concentration and the longest axial length out of the two eyes was found (r = −0.255, p = 0.0558). Further analysis revealed statistically significant differences in ET-1 concentration between patients with the axial length of the eye > 26 and ≤ 26 mm (p < 0.041) and patients with the axial length of the eye > 26 mm and controls (p < 0.001). ET-1 expression is disturbed in highly myopic children and adolescents. Lower ET-1 concentration in patients with the axial length of the eye > 26 mm may co-occur with high myopia and should be considered a risk factor in the pathophysiology of high myopia progression.
Characteristics of Circulating CD4+ T Cell Subsets in Patients with Mycobacterium avium Complex Pulmonary Disease
Authors: Han Sun Ae , Ko Yousang , Shin Sung Jae , Jhun Byung Woo
Published: May 2020

Although prevalence of Mycobacterium avium complex pulmonary disease (MAC-PD) is increasing, limited data are available regarding vulnerability to Mycobacterium avium complex (MAC) infections. To understand the pathobiology of interaction between MAC and host-immunity, it is important to understand the characteristics for circulating T cells in terms of the immunological phenotype and functional correlates in MAC-PD. We aimed to characterize immunophenotype, cytokine profile, and immune inhibitory receptors of circulating CD4+ T cells in MAC-PD patients. We enrolled 71 MAC-PD and 20 control individuals. Flow cytometric analysis was performed to determine T cell subsets and immune checkpoint markers. Ex vivo cytokine productions in response to MAC were determined using enzyme-linked immunosorbent assay. The frequencies of CD4+ T cells and CD4+IL-17+ T cells decreased, while CD4+IL-4+ T cells and CD4+CD25+Foxp3+ T cells increased in peripheral blood mononuclear cells (PBMCs) of MAC-PD individuals upon MAC stimulation compared with those cells in healthy donor-PBMCs. Additionally, we found increased PD-1, CTLA-4, and TIM-3-expressing T cells in MAC- PD individuals in response to MAC-stimulation, indicating that suppressed T cell-mediated response is associated with the susceptibility to MAC infection. These results may help to explain impaired T cell-mediated responses and pave the way for better strategies to achieve protective immunity against MAC infection.
Prognostic Value of Growth Differentiation Factor 15 in Kidney Donors and Recipients
Authors: Jehn Ulrich , Schütte-Nütgen Katharina , Henke Ute , Bautz Joachim , Pavenstädt Hermann , Suwelack Barbara , Reuter Stefan
Published: May 2020

Growth differentiation factor-15 (GDF15) is associated with inflammatory conditions, chronic kidney disease, cardiovascular disease and mortality. There is very limited data on GDF15 after kidney donation and transplantation. We analyzed serum samples of patients who donated a kidney (54 living donors) or who underwent kidney transplantation (104 recipients) at the University Hospital of Münster (Germany) between 2013 and 2015, for GDF15 levels immediately prior and one year after surgery. GDF15 levels were significantly elevated in end-stage renal disease patients compared to healthy individuals (2844 (IQR 2087, 3361) pg/ml vs. 384 (IQR 307, 487) pg/ml, p < 0.001). GDF15 was strongly associated with the dialysis vintage. While kidney transplantation led to a significant decrease of GDF15 (913 (IQR 674, 1453) pg/ml, p < 0.001), kidney donation caused a moderate increase of GDF15 (510 (IQR 420, 626), p < 0.001) one year after surgery. GDF15 levels remained significantly higher in recipients and kidney donors than in healthy controls (735 (IQR 536, 1202) pg/ml vs. 384 (IQR 307, 487) pg/ml, p < 0.001). GDF15 is increased in patients with kidney disease and is associated with dialysis vintage. Given its decrease after transplantation and its increase after uni-nephrectomy, GDF15 might be a marker of kidney function. However, since it correlates only to the eGFR in transplanted patients it may indicate chronic kidney disease.
Machine Learning Enables Prediction of Cardiac Amyloidosis by Routine Laboratory Parameters: A Proof-of-Concept Study
Authors: Agibetov Asan , Seirer Benjamin , Dachs Theresa-Marie , Koschutnik Matthias , Dalos Daniel , Rettl René , Duca Franz , Schrutka Lore , Agis Hermine , Kain Renate , Auer-Grumbach Michela , Binder Christina , Mascherbauer Julia , Hengstenberg Christian , Samwald Matthias , Dorffner Georg , Bonderman Diana
Published: May 2020

(1) Background: Cardiac amyloidosis (CA) is a rare and complex condition with poor prognosis. While novel therapies improve outcomes, many affected individuals remain undiagnosed due to a lack of awareness among clinicians. This study was undertaken to develop an expert-independent machine learning (ML) prediction model for CA relying on routinely determined laboratory parameters. (2) Methods: In a first step, we developed baseline linear models based on logistic regression. In a second step, we used an ML algorithm based on gradient tree boosting to improve our linear prediction model, and to perform non-linear prediction. Then, we compared the performance of all diagnostic algorithms. All prediction models were developed on a training cohort, consisting of patients with proven CA (positive cases, n = 121) and amyloidosis-unrelated heart failure (HF) patients (negative cases, n = 415). Performances of all prediction models were evaluated on a separate prognostic validation cohort with 37 CA-positive and 124 CA-negative patients. (3) Results: Our best model, based on gradient-boosted ensembles of decision trees, achieved an area under the receiver operating characteristic curve (ROC AUC) score of 0.86, with sensitivity and specificity of 89.2% and 78.2%, respectively. The best linear model had an ROC AUC score of 0.75, with sensitivity and specificity of 84.6 and 71.7, respectively. (4) Conclusions: Our work demonstrates that ML makes it possible to utilize basic laboratory parameters to generate a distinct CA-related HF profile compared with CA-unrelated HF patients. This proof-of-concept study opens a potential new avenue in the diagnostic workup of CA and may assist physicians in clinical reasoning.
Genome-Wide Analysis of the DNA Methylation Profile Identifies the Fragile Histidine Triad (FHIT) Gene as a New Promising Biomarker of Crohn’s Disease
Authors: Kim Tae-Oh , Park Dong-Il , Han Yu , Kang Keunsoo , Park Sae-Gwang , Park Hae , Yi Joo
Published: May 2020

Inflammatory bowel disease is known to be associated with a genetic predisposition involving multiple genes; however, there is growing evidence that abnormal interactions with environmental factors, particularly epigenetic factors, can also significantly contribute to the development of inflammatory bowel disease (IBD). Although many genome-wide association studies have been performed to identify the genetic changes underlying the pathogenesis of Crohn’s disease, the role of epigenetic alterations based on molecular complications arising from Crohn’s disease (CD) is poorly understood. We employed an unbiased approach to define DNA methylation alterations in colonoscopy samples from patients with CD using the HumanMethylation450K BeadChip platform. Technical and functional validation was performed by methylation-specific PCR (MSP) and bisulfite sequencing of a validation set of 207 patients with CD samples. Immunohistochemistry (IHC) analysis was performed in the representative sample sets. DNA methylation profile in CD revealed that 135 probes (24 hypermethylated and 111 hypomethylated probes) were differentially methylated. We validated the methylation levels of 19 genes that showed hypermethylation in patients with CD compared with normal controls. We uniquely identified that the fragile histidine triad (FHIT) gene was hypermethylated in a disease-specific manner and its protein level was downregulated in patients with CD. Pathway analysis of the hypermethylated candidates further suggested putative molecular interactions relevant to IBD pathology. Our data provide information on the biological and clinical implications of DNA hypermethylated genes in CD, identifying FHIT methylation as a promising new biomarker for CD. Further study of the role of FHIT in IBD pathogenesis may lead to the development of new therapeutic targets.
DNA Fragmentation in Viable and Non-Viable Spermatozoa Discriminates Fertile and Subfertile Subjects with Similar Accuracy
Authors: Muratori Monica , Pellegrino Giulia , Mangone Giusi , Azzari Chiara , Lotti Francesco , Tarozzi Nicoletta , Boni Luca , Borini Andrea , Maggi Mario , Baldi Elisabetta
Published: May 2020

Sperm DNA fragmentation (sDF) negatively affects reproduction and is traditionally detected in total sperm population including viable and non-viable spermatozoa. Here, we aimed at exploring the ability of DNA fragmentation to discriminate fertile and subfertile men when detected in viable (viable sDF), non-viable (non-viable sDF), and total spermatozoa (total sDF). We revealed sDF in 91 male partners of infertile couples and 71 fertile men (max 1 year from natural conception) with LiveTUNEL coupled to flow cytometry, able to reveal simultaneously DNA fragmentation and cell viability. We found that the three sDF parameters discriminated fertile and subfertile men with similar accuracy and independently from age and basal semen parameters: AUCs (area under the curves) (95% CI) were: 0.696 (0.615–0.776), p < 0.001 for total sDF; 0.718 (0.640–0.797), p < 0.001 for viable sDF; 0.760 (0.685–0.835), p < 0.001 for non-viable sDF. We also found that total and non-viable but not viable sDF significantly correlated to age and semen quality. In conclusion, the three sDF parameters similarly discriminated fertile and subfertile men. Viable spermatozoa with DNA fragmentation are likely cells able to fertilize the oocyte but failing to properly support subsequent embryo development. Non-viable sDF could be a sign of a subtler damage extended beyond the non-viable cells.
Consciousness and the Dimensionality of DOC Patients via the Generalized Ising Model
Authors: Abeyasinghe Pubuditha M. , Aiello Marco , Nichols Emily S. , Cavaliere Carlo , Fiorenza Salvatore , Masotta Orsola , Borrelli Pasquale , Owen Adrian M. , Estraneo Anna , Soddu Andrea
Published: May 2020

The data from patients with severe brain injuries show complex brain functions. Due to the difficulties associated with these complex data, computational modeling is an especially useful tool to examine the structure–function relationship in these populations. By using computational modeling for patients with a disorder of consciousness (DoC), not only we can understand the changes of information transfer, but we also can test changes to different states of consciousness by hypothetically changing the anatomical structure. The generalized Ising model (GIM), which specializes in using structural connectivity to simulate functional connectivity, has been proven to effectively capture the relationship between anatomical structures and the spontaneous fluctuations of healthy controls (HCs). In the present study we implemented the GIM in 25 HCs as well as in 13 DoC patients diagnosed at three different states of consciousness. Simulated data were analyzed and the criticality and dimensionality were calculated for both groups; together, those values capture the level of information transfer in the brain. Ratifying previous studies, criticality was observed in simulations of HCs. We were also able to observe criticality for DoC patients, concluding that the GIM is generalizable for DoC patients. Furthermore, dimensionality increased for the DoC group as compared to healthy controls, and could distinguish different diagnostic groups of DoC patients.
Functionalized Carbon Nanostructures Versus Drug Resistance: Promising Scenarios in Cancer Treatment
Authors: Curcio Manuela , Farfalla Annafranca , Saletta Federica , Valli Emanuele , Pantuso Elvira , Nicoletta Fiore Pasquale , Iemma Francesca , Vittorio Orazio , Cirillo Giuseppe
Published: May 2020

Carbon nanostructures (CN) are emerging valuable materials for the assembly of highly engineered multifunctional nanovehicles for cancer therapy, in particular for counteracting the insurgence of multi-drug resistance (MDR). In this regard, carbon nanotubes (CNT), graphene oxide (GO), and fullerenes (F) have been proposed as promising materials due to their superior physical, chemical, and biological features. The possibility to easily modify their surface, conferring tailored properties, allows different CN derivatives to be synthesized. Although many studies have explored this topic, a comprehensive review evaluating the beneficial use of functionalized CNT vs G or F is still missing. Within this paper, the most relevant examples of CN-based nanosystems proposed for MDR reversal are reviewed, taking into consideration the functionalization routes, as well as the biological mechanisms involved and the possible toxicity concerns. The main aim is to understand which functional CN represents the most promising strategy to be further investigated for overcoming MDR in cancer.
Kitamura Electrophilic Fluorination Using HF as a Source of Fluorine
Authors: Han Jianlin , Butler Greg , Moriwaki Hiroki , Konno Hiroyuki , Soloshonok Vadim A. , Kitamura Tsugio
Published: May 2020

This review article focused on the innovative procedure for electrophilic fluorination using HF and in situ generation of the required electrophilic species derived from hypervalent iodine compounds. The areas of synthetic application of this approach include fluorination of 1,3-dicarbonyl compounds, aryl-alkyl ketones, styrene derivatives, α,β-unsaturated ketones and alcohols, homoallyl amine and homoallyl alcohol derivatives, 3-butenoic acids and alkynes.
Effects of the Combination of β-Hydroxy-β-Methyl Butyrate and R(+) Lipoic Acid in a Cellular Model of Sarcopenia
Authors: Di Cesare Mannelli Lorenzo , Micheli Laura , Lucarini Elena , Parisio Carmen , Toti Alessandra , Tenci Barbara , Zanardelli Matteo , Branca Jacopo , Pacini Alessandra , Ghelardini Carla
Published: May 2020

Sarcopenia is a clinical problem associated with several pathological and non-pathological conditions. The aim of the present research is the evaluation of the pharmacological profile of the leucine metabolite β-hydroxy-β-methyl butyrate (HMB) associated with the natural R(+) stereoisomer of lipoic acid (R(+)LA) in a cellular model of muscle wasting. The C2C12 cell line is used as myoblasts or is differentiated in myotubes, sarcopenia is induced by dexamethasone (DEX). A Bonferroni significant difference procedure is used for a post hoc comparison. DEX toxicity (0.01–300 µM concentration range) is evaluated in myoblasts to measure cell viability and caspase 3 activation after 24 h and 48 h; cell incubation with 1 µM DEX for 48 h is chosen as optimal treatment for decreasing cell viability and increasing caspase 3 activity. R(+)LA or HMB significantly prevents DEX-induced cell mortality; the efficacy is improved when 100 µM R(+)LA is combined with 1 mM HMB. Regarding myoblasts, this combination significantly reduces DEX-evoked O2− production and protein oxidative damage. During the early phase of myotube formation, the mixture preserves the number of myogenin-positive cells, whereas it completely prevents the DEX-dependent damage in a later phase of myotube differentiation (7 days), as evaluated by cell diameter and percentage of multinucleated cells. R(+)LA in association with HMB is suggested for sarcopenia therapy.
Hybrid Imaging Agents for Pretargeting Applications Based on Fusarinine C—Proof of Concept
Authors: Summer Dominik , Petrik Milos , Mayr Sonja , Hermann Martin , Kaeopookum Piriya , Pfister Joachim , Klingler Maximilian , Rangger Christine , Haas Hubertus , Decristoforo Clemens
Published: May 2020

Hybrid imaging combining the beneficial properties of radioactivity and optical imaging within one imaging probe has gained increasing interest in radiopharmaceutical research. In this study, we modified the macrocyclic gallium-68 chelator fusarinine C (FSC) by conjugating a fluorescent moiety and tetrazine (Tz) moieties. The resulting hybrid imaging agents were used for pretargeting applications utilizing click reactions with a trans-cyclooctene (TCO) tagged targeting vector for a proof of principle both in vitro and in vivo. Starting from FSC, the fluorophores Sulfocyanine-5, Sulfocyanine-7, or IRDye800CW were conjugated, followed by introduction of one or two Tz motifs, resulting in mono and dimeric Tz conjugates. Evaluation included fluorescence microscopy, binding studies, logD, protein binding, in vivo biodistribution, µPET (micro-positron emission tomography), and optical imaging (OI) studies. 68Ga-labeled conjugates showed suitable hydrophilicity, high stability, and specific targeting properties towards Rituximab-TCO pre-treated CD20 expressing Raji cells. Biodistribution studies showed fast clearance and low accumulation in non-targeted organs for both SulfoCy5- and IRDye800CW-conjugates. In an alendronate-TCO based bone targeting model the dimeric IRDye800CW-conjugate resulted in specific targeting using PET and OI, superior to the monomer. This proof of concept study showed that the preparation of FSC-Tz hybrid imaging agents for pretargeting applications is feasible, making such compounds suitable for hybrid imaging applications.
Effect of Shading on Development, Yield and Quality of Bastard Balm Herb (Melittis melissophyllum L.)
Authors: Szymborska-Sandhu Izabela , Przybył Jarosław L. , Pióro-Jabrucka Ewelina , Jędrzejuk Agata , Węglarz Zenon , Bączek Katarzyna
Published: May 2020

The aim of the study was to assess the effects of Melittis melissophyllum shading on its development and accumulation of phenolics. Their content (verbascoside, apiin, luteolin-7-O-glucoside, coumarin, 3,4-dihydroxycoumarin, o-coumaric acid 2-O-glucoside as well as o-coumaric, p-coumaric, chlorogenic, caffeic, ferulic and cichoric acid) was determined in the herb using HPLC-DAD. The results showed that the content of abovementioned flavonoids and phenolic acids was highest in plants grown under full sunlight. On the other hand, a higher content of coumarin was observed in shaded plants, especially after the seed-setting stage. A similar tendency was noted for the amount of chlorophyll a and b. The content of hydrogen peroxide and malondialdehyde, the activity of polyphenol oxidase and catalase and the antioxidant capacity of plant extracts (measured using DPPH, ABTS and FRAP assays) were found to be the highest in the plants grown in full sunlight. However, the plants grown in moderate (30%) shade were found to thrive best.
Porosity at Different Structural Levels in Human and Yak Belly Hair and Its Effect on Hair Dyeing
Authors: Müllner Alexander R. M. , Pahl Ruben , Brandhuber Doris , Peterlik Herwig
Published: May 2020

Yak belly hair was proposed as a cheap substitute for human hair for the development of hair dyes, as its chemical composition closely resembles human hair in Raman spectroscopy. The absence of melanin in yak belly hair also leads to a strong reduction of fluorescence in Raman measurements, which is advantageous for the investigation of the effectivity of hair dyes. To assess the suitability for replacing human hair, we analyzed similarities and differences of both hair types with a variety of methods: Raman spectroscopy, to obtain molecular information; small-angle X-ray scattering to determine the nanostructure, such as intermediate filament distance, distance of lipid layers and nanoporosity; optical and scanning electron microscopy of surfaces and cross sections to determine the porosity at the microstructural level; and density measurements and tensile tests to determine the macroscopic structure, macroporosity and mechanical properties. Both types of hair are similar on a molecular scale, but differ on other length scales: yak belly hair has a smaller intermediate filament distance on the nanoscale. Most striking is a higher porosity of yak belly hair on all hierarchical levels, and a lower Young’s modulus on the macroscale. In addition to the higher porosity, yak belly hair has fewer overlapping scales of keratin, which further eases the uptake of coloring. This makes, on the other hand, a comparison of coloring processes difficult, and limits the usefulness of yak belly hair as a substitute for human hair.
Energetic Performance of Pure Silica Zeolites under High-Pressure Intrusion of LiCl Aqueous Solutions: An Overview
Authors: Confalonieri Giorgia , Daou T. Jean , Nouali Habiba , Arletti Rossella , Ryzhikov Andrey
Published: May 2020

An overview of all the studies on high-pressure intrusion—extrusion of LiCl aqueous solutions in hydrophobic pure silica zeolites (zeosils) for absorption and storage of mechanical energy is presented. Operational principles of heterogeneous lyophobic systems and their possible applications in the domains of mechanical energy storage, absorption, and generation are described. The intrusion of LiCl aqueous solutions instead of water allows to considerably increase energetic performance of zeosil-based systems by a strong rise of intrusion pressure. The intrusion pressure increases with the salt concentration and depends considerably on zeosil framework. In the case of channel-type zeosils, it rises with the decrease of pore opening diameter, whereas for cage-type ones, no clear trend is observed. A relative increase of intrusion pressure in comparison with water is particularly strong for the zeosils with narrow pore openings. The use of highly concentrated LiCl aqueous solutions instead of water can lead to a change of system behavior. This effect seems to be related to a lower formation of silanol defects under intrusion of solvated ions and a weaker interaction of the ions with silanol groups of zeosil framework. The influence of zeosil nanostructure on LiCl aqueous solutions intrusion–extrusion is also discussed.
Biphasic Dissolution as an Exploratory Method during Early Drug Product Development
Authors: Amaral Silva Daniela , Al-Gousous Jozef , Davies Neal M. , Bou Chacra Nadia , Webster Gregory K. , Lipka Elke , Amidon Gordon L. , Löbenberg Raimar
Published: May 2020

Dissolution testing is a major tool used to assess a drug product’s performance and as a quality control test for solid oral dosage forms. However, compendial equipment and methods may lack discriminatory power and the ability to simulate aspects of in vivo dissolution. Using low buffer capacity media combined with an absorptive phase (biphasic dissolution) increases the physiologic relevance of in vitro testing. The purpose of this study was to use non-compendial and compendial dissolution test conditions to evaluate the in vitro performance of different formulations. The United States Pharmacopeia (USP)-recommended dissolution method greatly lacked discriminatory power, whereas low buffer capacity media discriminated between manufacturing methods. The use of an absorptive phase in the biphasic dissolution test assisted in controlling the medium pH due to the drug removal from the aqueous medium. Hence, the applied non-compendial methods were more discriminative to drug formulation differences and manufacturing methods than conventional dissolution conditions. In this study, it was demonstrated how biphasic dissolution and a low buffer capacity can be used to assess in vitro drug product performance differences. This can be a valuable approach during the early stages of drug product development for investigating in vitro drug release with improved physiological relevance.
Phytoremediation Potential of Crop Plants in Countering Nickel Contamination in Carbonation Lime Coming from the Sugar Industry
Authors: De Bernardi Arianna , Casucci Cristiano , Businelli Daniela , D’Amato Roberto , Beone Gian Maria , Fontanella Maria Chiara , Vischetti Costantino
Published: May 2020

The phytoremediation potential of four crop species cultivated on carbonation lime coming from the sugar industry with water-soluble nickel (Ni) exceeding the Italian legal limit of 10 µg L−1 was assessed. Two autumn–winter species (spinach and canola) were tested with and without the addition of bentonite in a greenhouse experiment in order to overcome prolonged unfavourable weather conditions. Two spring-summer species (sunflower and sorghum) were grown in outdoor boxes. Plant species were selected among crops of interest for phytoremediation and their rotation throughout the year enable to maintain a permanent vegetation cover. Nickel concentration in different plant tissues and the concentrations of soluble and bioavailable Ni in lime were measured. In the greenhouse study, soluble Ni decreased below the legal limit in all the tests, and the combined effect of bentonite and plants reduced Ni in lime mainly in the bioavailable fraction. Spinach and sunflower emerged to be more suitable for phytoextraction than canola and sorghum, because of the higher concentration of the metal in the epigeal portions. The results from the outdoor experiment highlighted that sorghum has a good phytostabilisation potential since its ability to accumulate Ni mainly at the root level and to attract a significant amount of bioavailable Ni in the rhizosphere. This study arose from a real scenario of environmental contamination and investigated the potential of different approaches on the bioremediation of a specific industrial waste product.
Why Seed Physiology Is Important for Genebanking
Authors: Whitehouse Katherine J. , Hay Fiona R. , Lusty Charlotte
Published: May 2020

Genebank management is a field in its own right; it is multifaceted, requiring a diverse set of skills and knowledge. Seed physiology is one area that is critical to the successful operation of seed genebanks, requiring understanding of seed quality during development and maturation, seed dormancy and germination, and seed longevity in storage of the target species. Careful management of the workflow between these activities, as seeds move from harvest to storage, and the recording and management of all relevant associated data, is key to ensuring the effective conservation of plant genetic resources. This review will discuss various aspects of seed physiology that genebank managers should be aware of, to ensure appropriate decisions are made about the handling and management of their seed collections.