bluuebunny/crossref_metadata_2025 huggingface dataset:
An Objective Measure of Patellar Tendon Thickness Based on Ultrasonography and MRI in University Athletes
Authors: Nishida Yusuke , Nishino Tomofumi , Tanaka Kenta , Onishi Shinzo , Kanamori Akihiro , Yamazaki Masashi
Published: September 2021

Ultrasonography and MRI are used for imaging evaluation of patellar tendinopathy, and “thickening of the tendon” is known as one of the characteristic findings. However, there are no evidence-based quantitative criteria to help evaluate this phenomenon. The purpose of this study was to investigate an objective measure of patellar tendon thickness. Patellar tendon thickness was evaluated in 65 elite university athletes using both ultrasonography and MRI. The relationship between tendon thickness and clinical patellar tendinopathy was investigated, and the cutoff value of the tendon thickness was calculated. Of the 129 knees included in the analysis, clinical patellar tendinopathy was found in 16 knees (12.4%). The proximal patellar tendon was significantly thicker in athletes with clinical patellar tendinopathy on both ultrasonography (8.3 mm vs. 5.1 mm; p < 0.001) and MRI (9.9 mm vs. 5.5 mm; p < 0.001). Setting the cutoff value to a thickness of >7.0 mm was an accurate predictor of clinical patellar tendinopathy (ultrasonography: sensitivity 81.3%, specificity 95.6%; MRI: sensitivity 100%, specificity 89.4%). Both ultrasonography and MRI measurement of the proximal patellar tendon thickness reflected the presence of clinical patellar tendinopathy. Defining “thickening of the patellar tendon” as thicker than 7.0 mm on both ultrasonography and MRI therefore has clinical significance.
RBM20-Related Cardiomyopathy: Current Understanding and Future Options
Authors: Koelemen Jan , Gotthardt Michael , Steinmetz Lars M. , Meder Benjamin
Published: September 2021

Splice regulators play an essential role in the transcriptomic diversity of all eukaryotic cell types and organ systems. Recent evidence suggests a contribution of splice-regulatory networks in many diseases, such as cardiomyopathies. Adaptive splice regulators, such as RNA-binding motif protein 20 (RBM20) determine the physiological mRNA landscape formation, and rare variants in the RBM20 gene explain up to 6% of genetic dilated cardiomyopathy (DCM) cases. With ample knowledge from RBM20-deficient mice, rats, swine and induced pluripotent stem cells (iPSCs), the downstream targets and quantitative effects on splicing are now well-defined and the prerequisites for corrective therapeutic approaches are set. This review article highlights some of the recent advances in the field, ranging from aspects of granule formation to 3D genome architectures underlying RBM20-related cardiomyopathy. Promising therapeutic strategies are presented and put into context with the pathophysiological characteristics of RBM20-related diseases.
QRISK3 Performance in the Assessment of Cardiovascular Risk in Patients with Inflammatory Bowel Disease
Authors: Carrillo-Palau Marta , Hernández-Camba Alejandro , Ramos Laura , Vela Milagros , Arranz Laura , Hernández Alvarez-Buylla Noemi , Alonso-Abreu Inmaculada , Hernández-Pérez Anjara , Hernández-Guerra Manuel , Palazuelos Camilo , Llorca Javier , González-Gay Miguel Á. , Ferraz-Amaro Iván
Published: September 2021

Inflammatory bowel disease (IBD) has been described as an independent risk factor for the development of cardiovascular (CV) disease. Since the QRESEARCH risk estimator version 3 (QRISK3) calculator was recently proposed to assess CV in the general population, our objective was to compare the predictive ability of QRISK3 with that of a well-established European CV risk calculator, the Systematic Coronary Risk Assessment (SCORE), to identify the presence of subclinical carotid atherosclerosis in patients with IBD. In all, 186 patients with IBD and 178 controls were recruited. The presence of subclinical atherosclerosis was evaluated by carotid ultrasound to identify carotid plaque and the thickness of the carotid intima-media (cIMT). QRISK3 and SCORE were calculated. The relationship of QRISK3 and SCORE with each other and with the presence of subclinical carotid atherosclerosis (both carotid plaque and cIMT) was studied in patients and controls. SCORE (0.2 (interquartile range 0.1–0.9) vs. 0.4 (0.1–1.4), p = 0.55) and QRISK3 1.7 ((0.6–4.6) vs. 3.0 (1.0–7.8), p = 0.16) absolute values did not differ between patients and controls. QRISK3 and SCORE correlated equally with cIMT within both populations. However, SCORE correlation with cIMT was found to be significantly lower in patients with IBD when compared to controls (Spearman’s Rho 0.715 vs. 0.587, p = 0.034). Discrimination analysis of both calculators with carotid plaque was similar within both populations. Nevertheless, in patients with IBD, QRISK3 showed a trend toward a higher discrimination (QRISK3 area under the curve 0.812 (95%CI 0.748–0.875) vs. SCORE 0.790 (95%CI 0.723–0.856), p = 0.051). In conclusion, QRISK3 discrimination for subclinical atherosclerosis is optimal and equivalent to that of SCORE in IBD patients. However, our findings highlight the role of QRISK3 as an appropriate tool for the assessment of CV risk in patients with IBD.
Multiple Comorbidity Profile of Psychiatric Disorders in Epilepsy
Authors: Grzegorzewska Agata M. , Wiglusz Mariusz S. , Landowski Jerzy , Jakuszkowiak-Wojten Katarzyna , Cubała Wiesław J. , Włodarczyk Adam , Szarmach Joanna
Published: September 2021

The co-occurrence of psychiatric disorders in people with epilepsy (PWE) is not well documented or studied. Anxiety and depressive disorders are the most frequent comorbid disorders in PWE. In this paper, we characterized the rates of multiple psychiatric disorder comorbidity by reanalyzing data from a study sample of PWE. A total of 96 outpatient PWE completed the self-report symptom scale, and were diagnosed using the Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders (DSM-IV-TR) Axis I disorders (SCID-I). For analyses, patients were assigned to a comprehensive diagnostic group of anxiety and depressive disorders. In order to determine comorbidity across psychiatric diagnoses for the DSM-IV categories, Pearson’s chi-squared test (χ2) was used. In the study sample, eight patients (8.3% of the study sample, n = 96) had comorbid major depressive disorder and anxiety disorder. When looking at comorbidity of each diagnosis separately, it was determined that 50% of individuals with an anxiety disorder had comorbid Major Depressive Disorder (MDD) and 38% patients with MDD had comorbid anxiety disorder. This finding encourages a more systematic reporting of psychiatric prevalence data in epilepsy, especially taking into account the high ratio of multiple comorbid anxiety and depressive disorders in PWE.
Prevalence of Fatigue and Unrecognized Depression in Patients with Inflammatory Bowel Disease in Remission under Immunosuppressants and Biologicals
Authors: Truyens Marie , De Ruyck Elodie , Gonzales Gerard Bryan , Bos Simon , Laukens Debby , De Vos Martine
Published: September 2021

Background: Although highly prevalent among inflammatory bowel disease (IBD) patients, fatigue remains an unmet clinical need. The aim was to describe the prevalence of fatigue in an IBD population in remission and identify factors associated with fatigue. Methods: IBD patients in clinical and biochemical remission under treatment with immunomodulators or biologicals were included. Fatigue, physical tiredness and depression were assessed using the fatigue Visual Analogue Scale (fVAS), the Shortened Fatigue Questionnaire (SFQ) and the Quick Inventory of Depressive Symptomatology-Self Report (QIDS-SR), respectively. Relevant clinical and biochemical parameters were included in regression analyses to identify factors associated with physical fatigue. Results: In total, 157 IBD patients were included. Up to 45.9% of patients reported fatigue, physical tiredness was observed in 51% and depression in 10.8%. The majority of patients with subclinical depression were fatigued. Female sex (OR = 4.17 [1.55–6.78], p = 0.002) was independently associated with physical fatigue. Transferrin saturation (OR = −0.11 [−0.22–−0.007], p = 0.037) and treatment with adalimumab (compared to infliximab, OR = −3.65 [−7.21–−0.08], p = 0.045) entailed a lower risk of fatigue. Conclusion: Fatigue is observed in about half of IBD patients in remission and can be a symptom of underlying undetected depression. Sex, transferrin saturation and medication were identified as independent risk factors.
Change in the Strategy of Embryo Selection with Time-Lapse System Implementation—Impact on Clinical Pregnancy Rates
Authors: Boucret Lisa , Tramon Léa , Saulnier Patrick , Ferré-L’Hôtellier Véronique , Bouet Pierre-Emmanuel , May-Panloup Pascale
Published: September 2021

Time-lapse systems (TLS) and associated algorithms are interesting tools to improve embryo selection. This study aimed to evaluate how TLS and KIDScore™ algorithm changed our practices of embryo selection, as compared to a conventional morphological evaluation, and improved clinical pregnancy rates (CPR). In the study group (year 2020, n = 303 transfers), embryos were cultured in an EmbryoScope+ time-lapse incubator. A first team observed embryos conventionally once a day, while a second team selected the embryos for transfer based on time-lapse recordings. In the control group (year 2019, n = 279 transfers), embryos were selected using the conventional method, and CPR were recorded. In 2020, disagreement between TLS and the conventional method occurred in 32.1% of transfers, more often for early embryos (34.7%) than for blastocysts (20.5%). Irregular morphokinetic events (direct or reverse cleavage, multinucleation, abnormal pronuclei) were detected in 54.9% of the discordant embryos. When it was available, KIDScore™ was decreased for 73.2% of the deselected embryos. Discordant blastocysts mainly corresponded with a decrease in KIDScore™ (90.9%), whereas discordant Day 3 embryos resulted from a decreased KIDScore™ and/or an irregular morphokinetic event. CPR was significantly improved in the TLS group (2020), as compared to the conventional group (2019) (32.3% vs. 21.9%, p = 0.005), even after multivariate analysis. In conclusion, TLS is useful to highlight some embryo development abnormalities and identify embryos with the highest potential for pregnancy.
Assessment of Hyperglycemia, Hypoglycemia and Inter-Day Glucose Variability Using Continuous Glucose Monitoring among Diabetic Patients on Chronic Hemodialysis
Authors: Divani Maria , Georgianos Panagiotis I. , Didangelos Triantafyllos , Liakopoulos Vassilios , Makedou Kali , Iliadis Fotios , Savopoulos Christos , Grekas Dimitrios M.
Published: September 2021

Continuous glucose monitoring (CGM) facilitates the assessment of short-term glucose variability and identification of acute excursions of hyper- and hypo-glycemia. Among 37 diabetic hemodialysis patients who underwent 7-day CGM with the iPRO2 device (Medtronic Diabetes, Northridge, CA, USA), we explored the accuracy of glycated albumin (GA) and hemoglobin A1c (HbA1c) in assessing glycemic control, using CGM-derived metrics as the reference standard. In receiver operating characteristic (ROC) analysis, the area under the curve (AUC) in diagnosing a time in the target glucose range of 70–180 mg/dL (TIR70–180) in <50% of readings was higher for GA (AUC: 0.878; 95% confidence interval (CI): 0.728–0.962) as compared to HbA1c (AUC: 0.682; 95% CI: 0.508–0.825) (p < 0.01). The accuracy of GA (AUC: 0.939; 95% CI: 0.808–0.991) in detecting a time above the target glucose range > 250 mg/dL (TAR>250) in >10% of readings did not differ from that of HbA1c (AUC: 0.854; 95% CI: 0.699–0.948) (p = 0.16). GA (AUC: 0.712; 95% CI: 0.539–0.848) and HbA1c (AUC: 0.740; 95% CI: 0.570–0.870) had a similarly lower efficiency in detecting a time below target glucose range < 70 mg/dL (TBR<70) in >1% of readings (p = 0.71). Although the mean glucose levels were similar, the coefficient of variation of glucose recordings (39.2 ± 17.3% vs. 32.0 ± 7.8%, p < 0.001) and TBR<70 (median (range): 5.6% (0, 25.8) vs. 2.8% (0, 17.9)) were higher during the dialysis-on than during the dialysis-off day. In conclusion, the present study shows that among diabetic hemodialysis patients, GA had higher accuracy than HbA1c in detecting a 7-day CGM-derived TIR70–180 < 50%. However, both biomarkers provided an imprecise reflection of acute excursions of hypoglycemia and inter-day glucose variability.
Risk Factors for Acute Kidney Injury Requiring Renal Replacement Therapy after Orthotopic Heart Transplantation in Patients with Preserved Renal Function
Authors: M‘Pembele René , Roth Sebastian , Stroda Alexandra , Lurati Buse Giovanna , Sixt Stephan U. , Westenfeld Ralf , Polzin Amin , Rellecke Philipp , Tudorache Igor , Hollmann Markus W. , Aubin Hug , Akhyari Payam , Lichtenberg Artur , Huhn Ragnar , Boeken Udo
Published: September 2021

Acute kidney injury (AKI), requiring renal replacement therapy (RRT). is a serious complication after orthotopic heart transplantation (HTX). In patients with preexisting impaired renal function, postoperative AKI is unsurprising. However, even in patients with preserved renal function, AKI requiring RRT is frequent. Therefore, this study aimed to identify risk factors associated with postoperative AKI requiring RRT after HTX in this sub-cohort. This retrospective cohort study included patients ≥ 18 years of age with preserved renal function (defined as preoperative glomerular filtration rate ≥ 60 mL/min) who underwent HTX between 2010 and 2021. In total, 107 patients were included in the analysis (mean age 52 ± 12 years, 78.5% male, 45.8% AKI requiring RRT). Based on univariate logistic regression, use of extracorporeal membrane oxygenation, postoperative infection, levosimendan therapy, duration of norepinephrine (NE) therapy and maximum daily increase in tacrolimus plasma levels were chosen to be included into multivariate analysis. Duration of NE therapy and maximum daily increase in tacrolimus plasma levels remained as independent significant risk factors (NE: OR 1.01, 95%CI: 1.00–1.02, p = 0.005; increase in tacrolimus plasma level: OR 1.18, 95%CI: 1.01–1.37, p = 0.036). In conclusion, this study identified long NE therapy and maximum daily increase in tacrolimus plasma levels as risk factors for AKI requiring RRT in HTX patients with preserved renal function.
Lobular Breast Cancer Conspicuity on Digital Breast Tomosynthesis Compared to Synthesized 2D Mammography: A Multireader Study
Authors: Romanucci Giovanna , Zantedeschi Lisa , Ventriglia Anna , Mercogliano Sara , Bisighin Maria Vittoria , Cugola Loredana , Bricolo Paola , Rella Rossella , Mandarà Marta , Benassuti Chiara , Caneva Andrea , Fornasa Francesca
Published: September 2021

Objectives: To compare the conspicuity of lobular breast cancers at digital breast tomosynthesis (DBT) versus synthesized 2D mammography (synt2D). Materials and methods: Seventy-six women (mean age 61.2 years, range 50–74 years) submitted to biopsy in our institution, from 2019 to 2021, with proven invasive lobular breast cancer (ILC) were enrolled in this retrospective study. The participants underwent DBT and synt2D. Five breast radiologists, with different years of experience in breast imaging, independently assigned a conspicuity score (ordinal 6-point scale) to DBT and synt2D. Lesion conspicuity was compared, for each reader, between the synt2D overall conspicuity interpretation and DBT overall conspicuity interpretation using a Wilcoxon matched pairs test. Results: A total of 50/78 (64%) cancers were detected on both synt2D and DBT by all the readers, while 28/78 (26%) cancers where not recognized by at least one reader on synt2D. For each reader, in comparison with synt2D, DBT increased significantly the conspicuity of ILC (p < 0.0001). The raw proportion of high versus low conspicuity by modality confirmed that cancers were more likely to have high conspicuity at DBT than synt2D. Conclusions: ILCs were more likely to have high conspicuity at DBT than at synt2D, increasing the chances of the detection of ILC breast cancer.
Virulence Factors and in-Host Selection on Phenotypes in Infectious Probiotic Yeast Isolates (Saccharomyces ‘boulardii’)
Authors: Imre Alexandra , Kovács Renátó , Pázmándi Kitti , Nemes Dániel , Jakab Ágnes , Fekete Tünde , Rácz Hanna Viktória , Dóczi Ilona , Bácskay Ildikó , Gácser Attila , Kovács Károly , Majoros László , Farkas Zoltán , Pócsi István , Pfliegler Walter P.
Published: September 2021

Saccharomyces yeast probiotics (S. ‘boulardii’) have long been applied in the treatment of several gastrointestinal conditions. Despite their widespread use, they are rare opportunistic pathogens responsible for a high proportion of Saccharomyces mycosis cases. The potential virulence attributes of S. ‘boulardii’ as well as its interactions with the human immune system have been studied, however, no information is available on how these yeasts may change due to in-host evolution. To fill this gap, we compared the general phenotypic characteristics, cell morphology, virulence factors, epithelial and immunological interactions, and pathogenicity of four probiotic product samples, two mycosis, and eight non-mycosis samples of S. ‘boulardii’. We assessed the characteristics related to major steps of yeast infections. Mycosis and non-mycosis isolates both displayed novel characters when compared to the product isolates, but in the case of most virulence factors and in pathogenicity, differences were negligible or, surprisingly, the yeasts from products showed elevated levels. No isolates inflicted considerable damage to the epithelial model or bore the hallmarks of immune evasion. Our results show that strains in probiotic products possess characteristics that enable them to act as pathogens upon permissive conditions, and their entry into the bloodstream is not due to active mechanisms but depends on the host. Survival in the host is dependent on yeast phenotypic characteristics which may change in many ways once they start evolving in the host. These facts call attention to the shortcomings of virulence phenotyping in yeast research, and the need for a more thorough assessment of probiotic use.
Segmentation of Foreign Tourists Based on Emotional Perception—The Case of Granada, Spain
Authors: Valverde-Roda José , Solano-Sánchez Miguel Ángel , Aguilar-Rivero Minerva , Gomez-Casero Gema
Published: September 2021

The aim of the present research was to present the typologies of foreign tourists in the city of Granada, Spain, based on their emotional perception and interest in culture using different fieldwork methods. The main obtained results determine four segments of tourists: cultural, alternative, heritage, and emotional. The results also show that, in addition to cultural reasons, tourists presented other types of attractions that encouraged them to visit the city. Regarding the satisfaction variable, the obtained results show that satisfaction increased when cultural reasons had a strong influence on the tourists’ choice of destination. This research contributes to identifying the characteristics of the different visitor segments, with the aim of designing tourist and cultural products that can more efficiently satisfy their needs. This will have a positive impact on the economic development of the city of Granada with an increase in tourist spending, which will lead to an increase in employment and urban development.
Melibiose Confers a Neuroprotection against Cerebral Ischemia/Reperfusion Injury by Ameliorating Autophagy Flux via Facilitation of TFEB Nuclear Translocation in Neurons
Authors: Wu Zhiyuan , Zhang Yongjie , Liu Yuyuan , Chen Xuemei , Huang Zhiwen , Zhao Xiaoming , He Hongyun , Deng Yihao
Published: September 2021

Autophagic/lysosomal dysfunction is a critical pathogenesis of neuronal injury after ischemic stroke. Trehalose has been validated to restore the impaired autophagy flux by boosting transcription factor EB (TFEB) nuclear translocation, but orally administrated trehalose can be greatly digested by intestinal trehalase before entering into brain. Melibiose (MEL), an analogue of trehalose, may thoroughly exert its pharmacological effects through oral administration due to absence of intestinal melibiase. The present study was to investigate whether melibiose could also confer a neuroprotection by the similar pharmacological mechanism as trehalose did after ischemic stroke. The rats were pretreated with melibiose for 7 days before middle cerebral artery occlusion (MCAO) surgery. Twenty-four hours following MCAO/reperfusion, the cytoplasmic and nuclear TFEB, and the proteins in autophagic/lysosomal pathway at the penumbra were detected by western blot and immunofluorescence, respectively. Meanwhile, the neurological deficit, neuron survival, and infarct volume were assessed to evaluate the therapeutic outcomes. The results showed that the neurological injury was significantly mitigated in MCAO+MEL group, compared with that in MCAO group. Meanwhile, nuclear TFEB expression in neurons at the penumbra was significantly promoted by melibiose. Moreover, melibiose treatment markedly enhanced autophagy flux, as reflected by the reinforced lysosomal capacity and reduced autophagic substrates. Furthermore, the melibiose-elicited neuroprotection was prominently counteracted by lysosomal inhibitor Bafilomycin A1 (Baf-A1). Contrarily, reinforcement of lysosomal capacity with EN6 further improved the neurological performance upon melibiose treatment. Our data suggests that melibiose-augmented neuroprotection may be achieved by ameliorating autophagy flux via facilitation of TFEB nuclear translocation in neurons after ischemic stroke.
Diversity and Metabolic Potential of the Terrestrial Mud Volcano Microbial Community with a High Abundance of Archaea Mediating the Anaerobic Oxidation of Methane
Authors: Merkel Alexander Y. , Chernyh Nikolay A. , Pimenov Nikolai V. , Bonch-Osmolovskaya Elizaveta A. , Slobodkin Alexander I.
Published: September 2021

Terrestrial mud volcanoes (TMVs) are important natural sources of methane emission. The microorganisms inhabiting these environments remain largely unknown. We studied the phylogenetic composition and metabolic potential of the prokaryotic communities of TMVs located in the Taman Peninsula, Russia, using a metagenomic approach. One of the examined sites harbored a unique community with a high abundance of anaerobic methane-oxidizing archaea belonging to ANME-3 group (39% of all 16S rRNA gene reads). The high number of ANME-3 archaea was confirmed by qPCR, while the process of anaerobic methane oxidation was demonstrated by radioisotopic experiments. We recovered metagenome-assembled genomes (MAGs) of archaeal and bacterial community members and analyzed their metabolic capabilities. The ANME-3 MAG contained a complete set of genes for methanogenesis as well as of ribosomal RNA and did not encode proteins involved in dissimilatory nitrate or sulfate reduction. The presence of multiheme c-type cytochromes suggests that ANME-3 can couple methane oxidation with the reduction of metal oxides or with the interspecies electron transfer to a bacterial partner. The bacterial members of the community were mainly represented by autotrophic, nitrate-reducing, sulfur-oxidizing bacteria, as well as by fermentative microorganisms. This study extends the current knowledge of the phylogenetic and metabolic diversity of prokaryotes in TMVs and provides a first insight into the genomic features of ANME-3 archaea.
Cutaneous Metastasis from Colorectal Cancer: Making Light on an Unusual and Misdiagnosed Event
Authors: Parente Paola , Ciardiello Davide , Reggiani Bonetti Luca , Famiglietti Vincenzo , Cazzato Gerardo , Caramaschi Stefania , Attino Vito , Urbano Diego , Di Maggio Giuseppe , Ingravallo Giuseppe
Published: September 2021

Cutaneous metastasis from solid tumors is a rare event and usually represents a late occurrence in the natural history of an advanced visceral malignancy. Rarely, cutaneous metastasis has been described in colorectal cancer patients. The most frequent cutaneous site of colorectal metastasis is the surgical scar in the abdomen following the removal of the primary malignancy, followed by the extremities, perineum, head, neck, and penis. Metastases to the thigh and back of the trunk are anecdotical. Dermatological diagnosis of cutaneous metastasis can be quite complex, especially in unusual sites, such as in the facial skin or thorax and in cases of single cutaneous lesions since metastasis from colorectal cancer is not usually the first clinical hypothesis, leading to misdiagnosis. To date, due to the rarity of cutaneous metastasis from colorectal cancer, little evidence, most of which is based on case reports and very small case series, is currently available. Therefore, a better understanding of the clinic-pathological characteristics of this unusual metastatic site represents an unmet clinical need. We present a large series of 29 cutaneous metastases from colorectal cancer with particular concerns regarding anatomic localization and the time of onset with respect to primitive colorectal cancer and visceral metastases.
Artificial Neural Network Analysis of Gene Expression Data Predicted Non-Hodgkin Lymphoma Subtypes with High Accuracy
Authors: Carreras Joaquim , Hamoudi Rifat
Published: September 2021

Predictive analytics using artificial intelligence is a useful tool in cancer research. A multilayer perceptron neural network used gene expression data to predict the lymphoma subtypes of 290 cases of non-Hodgkin lymphoma (GSE132929). The input layer included both the whole array of 20,863 genes and a cancer transcriptome panel of 1769 genes. The output layer was lymphoma subtypes, including follicular lymphoma, mantle cell lymphoma, diffuse large B-cell lymphoma, Burkitt lymphoma, and marginal zone lymphoma. The neural networks successfully classified the cases consistent with the lymphoma subtypes, with an area under the curve (AUC) that ranged from 0.87 to 0.99. The most relevant predictive genes were LCE2B, KNG1, IGHV7_81, TG, C6, FGB, ZNF750, CTSV, INGX, and COL4A6 for the whole set; and ARG1, MAGEA3, AKT2, IL1B, S100A7A, CLEC5A, WIF1, TREM1, DEFB1, and GAGE1 for the cancer panel. The characteristic predictive genes for each lymphoma subtypes were also identified with high accuracy (AUC = 0.95, incorrect predictions = 6.2%). Finally, the topmost relevant 30 genes of the whole set, which belonged to apoptosis, cell proliferation, metabolism, and antigen presentation pathways, not only predicted the lymphoma subtypes but also the overall survival of diffuse large B-cell lymphoma (series GSE10846, n = 414 cases), and most relevant cancer subtypes of The Cancer Genome Atlas (TCGA) consortium including carcinomas of breast, colorectal, lung, prostate, and gastric, melanoma, etc. (7441 cases). In conclusion, neural networks predicted the non-Hodgkin lymphoma subtypes with high accuracy, and the highlighted genes also predicted the survival of a pan-cancer series.
A Hybrid Estimation of Distribution Algorithm for the Quay Crane Scheduling Problem
Authors: Pérez-Rodríguez Ricardo
Published: September 2021

The aim of the quay crane scheduling problem (QCSP) is to identify the best sequence of discharging and loading operations for a set of quay cranes. This problem is solved with a new hybrid estimation of distribution algorithm (EDA). The approach is proposed to tackle the drawbacks of the EDAs, i.e., the lack of diversity of solutions and poor ability of exploitation. The hybridization approach, used in this investigation, uses a distance based ranking model and the moth-flame algorithm. The distance based ranking model is in charge of modelling the solution space distribution, through an exponential function, by measuring the distance between solutions; meanwhile, the heuristic moth-flame determines who would be the offspring, with a spiral function that identifies the new locations for the new solutions. Based on the results, the proposed scheme, called QCEDA, works to enhance the performance of those other EDAs that use complex probability models. The dispersion results of the QCEDA scheme are less than the other algorithms used in the comparison section. This means that the solutions found by the QCEDA are more concentrated around the best value than other algorithms, i.e., the average of the solutions of the QCEDA converges better than other approaches to the best found value. Finally, as a conclusion, the hybrid EDAs have a better performance, or equal in effectiveness, than the so called pure EDAs.
Pharmacist-Led Medication Evaluation Considering Pharmacogenomics and Drug-Induced Phenoconversion in the Treatment of Multiple Comorbidities: A Case Report
Authors: Del Toro-Pagán Nicole Marie , Matos Adriana , Thacker David , Turgeon Jacques , Amin Nishita Shah , Michaud Veronique
Published: September 2021

Pharmacogenomic (PGx) information can guide drug and dose selection, optimize therapy outcomes, and/or decrease the risk of adverse drug events (ADEs). This report demonstrates the impact of a pharmacist-led medication evaluation, with PGx assisted by a clinical decision support system (CDSS), of a patient with multiple comorbidities. Following several sub-optimal pharmacotherapy attempts, PGx testing was recommended. The results were integrated into the CDSS, which supported the identification of clinically significant drug–drug, drug–gene, and drug–drug–gene interactions that led to the phenoconversion of cytochrome P450. The pharmacist evaluated PGx results, concomitant medications, and patient-specific factors to address medication-related problems. The results identified the patient as a CYP2D6 intermediate metabolizer (IM). Duloxetine-mediated competitive inhibition of CYP2D6 resulted in phenoconversion, whereby the patient’s CYP2D6 phenotype was converted from IM to poor metabolizer for CYP2D6 co-medication. The medication risk score suggested a high risk of ADEs. Recommendations that accounted for PGx and drug-induced phenoconversion were accepted. After 1.5 months, therapy changes led to improved pain control, depression status, and quality of life, as well as increased heart rate, evidenced by patient-reported improved sleep patterns, movement, and cognition. This case highlights the pharmacist’s role in using PGx testing and a CDSS to identify and mitigate medication-related problems to optimize medication regimen and medication safety.
Surface Plasmon Resonance-Based Immunosensor for Igm Detection with Gold Nanoparticles
Authors: Bereli Nilay , Bakhshpour Monireh , Topçu Aykut Arif , Denizli Adil
Published: September 2021

In this work, a surface plasmon resonance (SPR) based immunosensor was prepared by the immobilization of the amine-functionalized gold nanoparticles (N-AuNPs) on the sensing surface to sense immunoglobulin M (IgM) antibodies in the aqueous solution and artificial plasma. The characterization studies of SPR based immunosensor for IgM detection were performed with scanning electron microscope (SEM), contact angle measurements, and ellipsometry. Kinetic studies for the IgM immunosensor were carried out in the range of 1.0 to 200 ng/mL IgM concentrations in an aqueous solution. The total IgM analysis time including adsorption, desorption, and regeneration cycles was nearly 10 min for the prepared immunosensor. The limit of detection (LOD) and limit of quantification (LOQ) were found as 0.08 and 0.26 ng/mL, respectively. The reusability of the proposed immunosensor was tested with 6 consecutive adsorption-desorption, and regeneration cycles. Also, enzyme-linked immunosorbent assay (ELISA) method was utilized in the validation of the immunosensor.
Reverse Design of On-Chip Terahertz Demultiplexers
Authors: Zhu Guofeng , Huang Feng , Dai Zhenrong , Ju Xuewei , Zhong Shuncong , Wang Xiangfeng
Published: September 2021

The reverse design method (RDM) is a frontier direction in the optical research field. In this work, RDM is applied to the design of terahertz demultiplexers, including two-port and three-port terahertz demultiplexers, with areas of 3 mm × 3 mm and 5 mm × 5 mm, respectively. The Finite-Difference Time-Domain (FDTD) simulation results show that the terahertz waves at frequencies of 0.5 THz and 0.417 THz can be well separated by the two-port demultiplexer, and the transmittances of the two outputs reach as high as 0.75 after bandwidth optimization. Meanwhile, the three-port terahertz demultiplexer can have terahertz waves separated from three Ports, and the crosstalk between adjacent channels is less than −18 dB.
DNA Studies: Latest Spectroscopic and Structural Approaches
Authors: Marini Monica , Legittimo Francesca , Torre Bruno , Allione Marco , Limongi Tania , Scaltrito Luciano , Pirri Candido Fabrizio , di Fabrizio Enzo
Published: September 2021

This review looks at the different approaches, techniques, and materials devoted to DNA studies. In the past few decades, DNA nanotechnology, micro-fabrication, imaging, and spectroscopies have been tailored and combined for a broad range of medical-oriented applications. The continuous advancements in miniaturization of the devices, as well as the continuous need to study biological material structures and interactions, down to single molecules, have increase the interdisciplinarity of emerging technologies. In the following paragraphs, we will focus on recent sensing approaches, with a particular effort attributed to cutting-edge techniques for structural and mechanical studies of nucleic acids.
Unique Tubulin-Based Structures in the Zoonotic Apicomplexan Parasite Cryptosporidium parvum
Authors: Wang Chenchen , Wang Dongqiang , Nie Jiawen , Gao Xin , Yin Jigang , Zhu Guan
Published: September 2021

Cryptosporidium parasites are known to be highly divergent from other apicomplexan species at evolutionary and biological levels. Here we provide evidence showing that the zoonotic Cryptosporidium parvum also differs from other apicomplexans, such as Toxoplasma gondii, by possessing only two tubulin-based filamentous structures, rather than an array of subpellicular microtubules. Using an affinity-purified polyclonal antibody against C. parvum β-tubulin (CpTubB), we observed a long and a short microtubule that are rigid and stable in the sporozoites and restructured during the intracellular parasite development. In asexual development (merogony), the two restructuring microtubules are present in pairs (one pair per nucleus or merozoites). In sexual developmental stages, tubulin-based structures are detectable only in microgametes, but undetectable in macrogametes. These observations indicate that C. parvum parasites use unique microtubule structures that differ from other apicomplexans as part of their cytoskeletal elements.
From Strain Characterization to Field Authorization: Highlights on Bacillus velezensis Strain B25 Beneficial Properties for Plants and Its Activities on Phytopathogenic Fungi
Authors: Joly Pierre , Calteau Alexandra , Wauquier Aurélie , Dumas Rémi , Beuvin Mylène , Vallenet David , Crovadore Julien , Cochard Bastien , Lefort François , Berthon Jean-Yves
Published: September 2021

Agriculture is in need of alternative products to conventional phytopharmaceutical treatments from chemical industry. One solution is the use of natural microorganisms with beneficial properties to ensure crop yields and plant health. In the present study, we focused our analyses on a bacterium referred as strain B25 and belonging to the species Bacillus velezensis (synonym B. amyloliquefaciens subsp. plantarum or B. methylotrophicus), a promising plant growth promoting rhizobacterium (PGPR) and an inhibitor of pathogenic fungi inducing crops diseases. B25 strain activities were investigated. Its genes are well preserved, with their majority being common with other Bacillus spp. strains and responsible for the biosynthesis of secondary metabolites known to be involved in biocontrol and plant growth-promoting activities. No antibiotic resistance genes were found in the B25 strain plasmid. In vitro and in planta tests were conducted to confirm these PGPR and biocontrol properties, showing its efficiency against 13 different pathogenic fungi through antibiosis mechanism. B25 strain also showed good capacities to quickly colonize its environment, to solubilize phosphorus and to produce siderophores and little amounts of auxin-type phytohormones (around 13,051 µg/mL after 32 h). All these findings combined to the fact that B25 demonstrated good properties for industrialization of the production and an environmental-friendly profile, led to its commercialization under market authorization since 2018 in several biostimulant preparations and opened its potential use as a biocontrol agent.
Artificial Rearing of Atlantic Salmon Juveniles for Supportive Breeding Programs Induces Long-Term Effects on Gut Microbiota after Stocking
Authors: Lavoie Camille , Wellband Kyle , Perreault Alysse , Bernatchez Louis , Derome Nicolas
Published: September 2021

In supportive breeding programs for wild salmon populations, stocked parr experience higher mortality rates than wild ones. Among other aspects of phenotype, the gut microbiota of artificially raised parr differs from that of wild parr before stocking. Early steps of microbiota ontogeny are tightly dependent upon environmental conditions, both of which exert long-term effects on host physiology. Therefore, our objective was to assess to what extent the resilience capacity of the microbiota of stocked salmon may prevent taxonomic convergence with that of their wild congeners after two months in the same natural environment. Using the 16S SSU rRNA marker gene, we tested the general hypothesis that environmental conditions during the very first steps of microbiota ontogeny imprint a permanent effect on later stages of microbiota recruitment. Our results first showed that gut microbiota composition of stocked and wild parr from the same genetic population, and sharing the same environment, was dependent on the early rearing environment. In contrast, skin microbiota in stocked individuals converged to that of wild individuals. Taxonomic composition and co-occurrence network analyses suggest an impairment of wild bacteria recruitment and a higher instability for the gut microbiota of stocked parr. This study is the first to demonstrate the long-term effect of early microbiota ontogeny in artificial rearing for natural population conservation programs, raising the need to implement microbial ecology.
Ligilactobacillus salivarius PS2 Supplementation during Pregnancy and Lactation Prevents Mastitis: A Randomised Controlled Trial
Authors: Jiménez Esther , Manzano Susana , Schlembach Dietmar , Arciszewski Krzysztof , Martin Rocio , Ben Amor Kaouther , Roelofs Mieke , Knol Jan , Rodríguez Juan Miguel , Abou-Dakn Michael ,   PREMIUM Study Group
Published: September 2021

Mastitis is considered one of the main reasons for unwanted breastfeeding cessation. This study aimed to investigate the preventive effect of the probiotic strain Ligilactobacillus salivarius PS2 on the occurrence of mastitis in lactating women. In this multicountry, multicenter, randomized, double-blind, placebo-controlled trial, 328 women were assigned to the probiotic or the placebo group. The intervention started from the 35th week of pregnancy until week 12 post-partum. The primary outcome was the incidence (hazard) rate of mastitis, defined as the presence of at least two of the following symptoms: breast pain, breast erythema, breast engorgement not relieved by breastfeeding, and temperature > 38 °C. The probability of being free of mastitis during the study was higher in the probiotic than in the placebo group (p = 0.022, Kaplan–Meier log rank test) with 9 mastitis cases (6%) vs. 20 mastitis cases (14%), respectively. The hazard ratio of the incidence of mastitis between both study groups was 0.41 (0.190–0.915; p = 0.029), indicating that women in the probiotic group were 58% less likely to experience mastitis. In conclusion, supplementation of L. salivarius PS2 during late pregnancy and early lactation was safe and effective in preventing mastitis, which is one of the main barriers for continuing breastfeeding.
Factors Associated with Prolonged Hospital Length of Stay in Adults with Imported Falciparum Malaria—An Observational Study from a Tertiary Care University Hospital in Berlin, Germany
Authors: Hoffmeister Bodo
Published: September 2021

Outcome of falciparum malaria is largely influenced by the standard of care provided, which in turn depends on the available medical resources. Worldwide, the COVID-19 pandemic has had a major impact on the availability of these resources, even in resource-rich healthcare systems such as Germany’s. The present study aimed to determine the under-explored factors associated with hospital length of stay (LOS) in imported falciparum malaria to identify potential targets for improving management. This retrospective observational study used multivariate Cox proportional hazard regression with time to discharge as an endpoint for adults hospitalized between 2001 and 2015 with imported falciparum malaria in the Charité University Hospital, Berlin. The median LOS of the 535 cases enrolled was 3 days (inter-quartile range, IQR, 3–4 days). The likelihood of being discharged by day 3 strongly decreased with severe malaria (hazard ratio, HR, 0.274; 95% Confidence interval, 95%CI: 0.190–0.396) and by 40% with each additional presenting complication (HR, 0.595; 95%CI: 0.510–0.694). The 55 (10.3%) severe cases required a median LOS of 7 days (IQR, 5–12 days). In multivariate analysis, occurrence of shock (adjusted HR, aHR, 0.438; 95%CI 0.220–0.873), acute pulmonary oedema or acute respiratory distress syndrome (aHR, 0.450; 95%CI: 0.223–0.874), and the need for renal replacement therapy (aHR, 0.170; 95%CI: 0.063–0.461) were independently associated with LOS. All patients survived to discharge. This study illustrates that favourable outcomes can be achieved with high-standard care in imported falciparum malaria. Early recognition of disease severity together with targeted supportive care can lead to avoidance of manifest organ failure, thereby potentially decreasing LOS and alleviating pressure on bed capacities.
Investigation of Source Rock Heating and Structural Changes in the Electromagnetic Fields Using Experimental and Mathematical Modeling
Authors: Kovaleva Liana , Zinnatullin Rasul , Musin Airat , Kireev Victor , Karamov Tagir , Spasennykh Mikhail
Published: September 2021

The paper presents the results of an experimental study of heating and the structural resultant changes of source rocks under the influence of the electromagnetic field in the microwave and radio-frequency ranges. The samples from the Bazhenov Formation (West Siberia, Russia) and the Domanic Formation (Ural, Russia) have been tested. It is shown that samples from these formations demonstrate very different heating rates at the same electromagnetic field parameters and the their heating rate depends on the type of the electromagnetic field (radio-frequency or microwave) applied. The temperature of the Bazhenov Formation samples reaches 300 °C within one hundred seconds of the microwave treatment but it slowly rises to 200 °C after twelve minutes of the radio-frequency influence. The samples of the carbonate Domanic Formation heat up more slowly in the microwave field (within two hundred seconds) and to lower temperatures in the radio-frequency (150 °C) than the Bazhenov Formation samples. The study of the structure of the samples before and after experiments on the electromagnetic treatment shows fracture formation during the heating process. Numerical simulations of heating dynamics of source rock samples have been based on a simple mathematical model of the electromagnetic influence and main features of heating for different types of source rock have been revealed. The opportunities for application of electromagnetic heating for oil source rock recovery are discussed.
Polypeptide N-acetylgalactosaminyltransferase-Associated Phenotypes in Mammals
Authors: Kato Kentaro , Hansen Lars , Clausen Henrik
Published: September 2021

Mucin-type O-glycosylation involves the attachment of glycans to an initial O-linked N-acetylgalactosamine (GalNAc) on serine and threonine residues on proteins. This process in mammals is initiated and regulated by a large family of 20 UDP-GalNAc: polypeptide N-acetylgalactosaminyltransferases (GalNAc-Ts) (EC 2.4.1.41). The enzymes are encoded by a large gene family (GALNTs). Two of these genes, GALNT2 and GALNT3, are known as monogenic autosomal recessive inherited disease genes with well characterized phenotypes, whereas a broad spectrum of phenotypes is associated with the remaining 18 genes. Until recently, the overlapping functionality of the 20 members of the enzyme family has hindered characterizing the specific biological roles of individual enzymes. However, recent evidence suggests that these enzymes do not have full functional redundancy and may serve specific purposes that are found in the different phenotypes described. Here, we summarize the current knowledge of GALNT and associated phenotypes.
A Themed Issue in Honor of Professor K. Hüsnü Can Baser—Outstanding Contributions in the Fields of Pharmacognosy, Phytochemistry, Botany and Ethnopharmacology
Authors: Çalış İhsan , Horváth Györgyi , Ludwiczuk Agnieszka
Published: September 2021

Dear Colleagues, [...]
Glucosylation of (±)-Menthol by Uridine-Diphosphate-Sugar Dependent Glucosyltransferases from Plants
Authors: Kurze Elisabeth , Ruß Victoria , Syam Nadia , Effenberger Isabelle , Jonczyk Rafal , Liao Jieren , Song Chuankui , Hoffmann Thomas , Schwab Wilfried
Published: September 2021

Menthol is a cyclic monoterpene alcohol of the essential oils of plants of the genus Mentha, which is in demand by various industries due to its diverse sensorial and physiological properties. However, its poor water solubility and its toxic effect limit possible applications. Glycosylation offers a solution as the binding of a sugar residue to small molecules increases their water solubility and stability, renders aroma components odorless and modifies bioactivity. In order to identify plant enzymes that catalyze this reaction, a glycosyltransferase library containing 57 uridine diphosphate sugar-dependent enzymes (UGTs) was screened with (±)-menthol. The identity of the products was confirmed by mass spectrometry and nuclear magnetic resonance spectroscopy. Five enzymes were able to form (±)-menthyl-β-d-glucopyranoside in whole-cell biotransformations: UGT93Y1, UGT93Y2, UGT85K11, UGT72B27 and UGT73B24. In vitro enzyme activity assays revealed highest catalytic activity for UGT93Y1 (7.6 nkat/mg) from Camellia sinensis towards menthol and its isomeric forms. Although UGT93Y2 shares 70% sequence identity with UGT93Y1, it was less efficient. Of the five enzymes, UGT93Y1 stood out because of its high in vivo and in vitro biotransformation rate. The identification of novel menthol glycosyltransferases from the tea plant opens new perspectives for the biotechnological production of menthyl glucoside.
Impact of Xylose on Dynamics of Water Diffusion in Mesoporous Zeolites Measured by NMR
Authors: Nelson Madison L. , Romo Joelle E. , Wettstein Stephanie G. , Seymour Joseph D.
Published: September 2021

Zeolites are known to be effective catalysts in biomass converting processes. Understanding the mesoporous structure and dynamics within it during such reactions is important in effectively utilizing them. Nuclear magnetic resonance (NMR) T2 relaxation and diffusion measurements, using a high-power radio frequency probe, are shown to characterize the dynamics of water in mesoporous commercially made 5A zeolite beads before and after the introduction of xylose. Xylose is the starting point in the dehydration into furfural. The results indicate xylose slightly enhances rotational mobility while it decreases translational motion through altering the permeability, K, throughout the porous structure. The measurements show xylose inhibits pure water from relocating into larger pores within the zeolite beads where it eventually is expelled from the bead itself.