bluuebunny/crossref_metadata_2025 huggingface dataset:
The Clinical Utility of D-Dimer and Prothrombin Fragment (F1+2) for Peripheral Artery Disease: A Prospective Study
Authors: Arfan Sara , Zamzam Abdelrahman , Syed Muzammil H. , Jain Shubha , Jahanpour Niousha , Abdin Rawand , Qadura Mohammad
Published: April 2022

D-dimer and prothrombin fragment (F1+2) levels are elevated in patients with peripheral artery disease (PAD). We examined their prognostic potential in predicting decreasing ABI and major adverse limb events (MALE). A total of 206 patients were recruited from St. Michael’s Hospital and followed for two years. Baseline plasma concentrations of D-dimer and F1+2 were recorded. Pearson’s correlation was used to assess the correlation between the biomarkers and ABI at year 2. During follow-up, multivariable Cox proportional hazard analysis was performed to investigate their role in predicting decreasing ABI (defined as change in ABI > −0.15) and MALE (defined as the need for arterial intervention or major limb amputation). Cumulative survival was assessed using Kaplan–Meier analysis. Baseline D-dimer and F1+2 levels were elevated in PAD patients (median (IQR) 1.34 (0.80–2.20) for D-dimer and 3.60 (2.30–4.74) for F1+2; p = 0.001) compared to non-PAD controls (median (IQR) 0.69 (0.29–1.20) for D-dimer and 1.84 (1.17–3.09) for F1+2; p = 0.001). Both markers were negatively correlated with ABI at year 2 (r = −0.231 for D-dimer, r = −0.49 for F1+2; p = 0.001). Cox analysis demonstrated F1+2 and D-dimer to be independent predictors of PAD status (HR = 1.27, 95% CI = 1.15–1.54; p = 0.013 for D-dimer and HR = 1.28, 95% CI = 1.14–1.58; p = 0.019 for F1+2). Elevated baseline concentrations of D-dimer and F1+2 were associated with high incidence of decreasing ABI and 1- and 2-year event-free survival (62% and 86%, respectively). Combined analysis of D-dimer and F1+2 provides important prognostic information that facilitates risk stratification for future disease progression and MALE outcomes in patients with PAD.
Machine Learning-Based Retention Time Prediction of Trimethylsilyl Derivatives of Metabolites
Authors: de Cripan Sara M. , Cereto-Massagué Adrià , Herrero Pol , Barcaru Andrei , Canela Núria , Domingo-Almenara Xavier
Published: April 2022

In gas chromatography–mass spectrometry-based untargeted metabolomics, metabolites are identified by comparing mass spectra and chromatographic retention time with reference databases or standard materials. In that sense, machine learning has been used to predict the retention time of metabolites lacking reference data. However, the retention time prediction of trimethylsilyl derivatives of metabolites, typically analyzed in untargeted metabolomics using gas chromatography, has been poorly explored. Here, we provide a rationalized framework for machine learning-based retention time prediction of trimethylsilyl derivatives of metabolites in gas chromatography. We compared different machine learning paradigms, in addition to exploring the influence of the computational molecular structure representation to train the prediction models: fingerprint class and fingerprint calculation software. Our study challenged predicted retention time when using chemical ionization and electron impact ionization sources in simulated and real cases, demonstrating a good correct identity ranking capability by machine learning, despite observing a limited false identity filtering power in cases where a spectrum or a monoisotopic mass match to multiple candidates. Specifically, machine learning prediction yielded median absolute and relative retention index (relative retention time) errors of 37.1 retention index units and 2%, respectively. In addition, fingerprint class and fingerprint calculation software, as well as the molecular structural similarity between the training and test or real case sets, showed to be critical modulators of the prediction performance. Finally, we leveraged the structural similarity between the training and test or real case set to determine the probability that the prediction error is below a specific threshold. Overall, our study demonstrates that predicted retention time can provide insights into the true structure of unknown metabolites by ranking from the most to the least plausible molecular identity, and sets the guidelines to assess the confidence in metabolite identification using predicted retention time data.
Mitochondrial Genetics Reinforces Multiple Layers of Interaction in Alzheimer’s Disease
Authors: Cavalcante Giovanna Chaves , Brito Leonardo Miranda , Schaan Ana Paula , Ribeiro-dos-Santos Ândrea , de Araújo Gilderlanio Santana ,   on behalf of Alzheimer’s Disease Neuroimaging Initiative
Published: April 2022

Nuclear DNA has been the main source of genome-wide loci association in neurodegenerative diseases, only partially accounting for the heritability of Alzheimer’s Disease (AD). In this context, mitochondrial DNA (mtDNA) is gaining more attention. Here, we investigated mitochondrial genes and genetic variants that may influence mild cognitive impairment and AD, through an integrative analysis including differential gene expression and mitochondrial genome-wide epistasis. We assessed the expression of mitochondrial genes in different brain tissues from two public RNA-Seq databases (GEO and GTEx). Then, we analyzed mtDNA from the ADNI Cohort and investigated epistasis regarding mitochondrial variants and levels of Aβ1−42, TAU, and Phosphorylated TAU (PTAU) from cognitively healthy controls, and both mild cognitive impairment (MCI) and AD cases. We identified multiple differentially expressed mitochondrial genes in the comparisons between cognitively healthy individuals and AD patients. We also found increased protein levels in MCI and AD patients when compared to healthy controls, as well as novel candidate networks of mtDNA epistasis, which included variants in all mitochondrially-encoded oxidative phosphorylation complexes, 12S rRNA and MT-DLOOP. Our results highlight layers of potential interactions involving mitochondrial genetics and suggest specific molecular alterations as potential biomarkers for AD.
Eye Movement Abnormalities in Amyotrophic Lateral Sclerosis
Authors: Guo Xintong , Liu Xiaoxuan , Ye Shan , Liu Xiangyi , Yang Xu , Fan Dongsheng
Published: April 2022

It is generally believed that eye movements are completely spared in amyotrophic lateral sclerosis (ALS). Although a series of eye movement abnormalities has been recognized in recent years, the findings are highly controversial, and bulbar disabilities should be considered in relation to eye movement abnormalities. The present study aimed to determine whether eye movement abnormalities are present in ALS and, if so, to investigate their characteristics and their association with bulbar disability in ALS patients. A total of 60 patients and 30 controls were recruited and underwent the standardized evaluations of the oculomotor system using videonystagmography. Square-wave jerks (OR: 16.20, 95% CI: 3.50–74.95, p < 0.001) and abnormal cogwheeling during smooth pursuit (OR: 14.04, 95% CI: 3.00–65.75, p = 0.001) were more frequently observed in ALS patients than in the control subjects. In subgroup analyses, square-wave jerks (OR: 26.51, 95% CI: 2.83–248.05, p = 0.004) and abnormal cogwheeling during smooth pursuit (OR: 6.56, 95% CI: 1.19–36.16, p = 0.031) were found to be more common in ALS patients with bulbar involvement (n = 44) than in those without bulbar involvement (n = 16). There were no significant differences in the investigated eye movement parameters between bulbar-onset (n = 12) and spinal-onset patients (n = 48). ALS patients showed a range of eye movement abnormalities, affecting mainly the ocular fixation and smooth pursuit systems. Our pioneering study indicates that the region of involvement could better indicate the pathophysiological essence of the abnormalities than the type of onset pattern in ALS. Eye movement abnormalities may be potential clinical markers for objectively evaluating upper brainstem or supratentorial cerebral lesion neurodegeneration in ALS.
SIRT1 Interacts with Prepro-Orexin in the Hypothalamus in SOD1G93A Mice
Authors: Zhang Gan , Liu Rong , Sheng Zhaofu , Zhang Yonghe , Fan Dongsheng
Published: April 2022

The participation of silent mating type information regulation 2 homolog 1 (SIRT1) in amyotrophic lateral sclerosis (ALS) has been reported in many studies. However, the role of the expression and function of SIRT1 in the hypothalamus in ALS remains unknown. In the current study, we performed western blot, co-immunoprecipitation and immunofluorescence analyses to determine the expression and in-depth mechanism of SIRT1 in the hypothalamus in SOD1G93A transgenic mice. We found that SIRT1 was overexpressed in the hypothalamus after motor symptom onset. In addition, SIRT1 interacted with prepro-orexin, a molecule involved in energy balance and the sleep/wake cycle, in both preclinical and clinical ALS regardless of whether SIRT1 levels were elevated. These findings indicate that SIRT1 might participate in sleep and metabolic changes in ALS, suggesting that SIRT1 is a new target for ALS treatment.
Cluster B versus Cluster C Personality Disorders: A Comparison of Comorbidity, Suicidality, Traumatization and Global Functioning
Authors: Massaal-van der Ree Laura Y. , Eikelenboom Merijn , Hoogendoorn Adriaan W. , Thomaes Kathleen , van Marle Hein J. F.
Published: April 2022

A general clinical assumption states that cluster B personality disorders (PDs) represent a more severe form of PD than cluster C PDs. Consequently, most PD research is centered on cluster B PDs (especially borderline PD). Yet, prevalence ratings of cluster C PDs exceed those of cluster B PDs. In this explorative, cross-sectional study, we compared cluster B and C PD patients (N = 94) on a wide range of clinically-relevant severity measures, including comorbidity, suicidality, (childhood) traumatization and global functioning. Results showed that, although cluster B PD patients suffered more often from substance use disorders and lifetime suicide attempts, no difference could be established between groups for all other severity measures, including trauma variables. In our study, we additionally included a group of combined cluster B and C PDs, who were largely similar to both other groups. Although our study is insufficiently powered to claim a significant non-difference, these findings emphasize that high rates of comorbidity, suicidality, childhood traumatization and functional impairment apply to both cluster B and C patients. As such, our findings encourage more research into cluster C PDs, ultimately leading to more evidence-based treatments for this prevalent patient group. In addition, the high level of traumatization across groups calls for a routine trauma screening, especially since PD treatment may benefit from concurrent trauma treatment.
Application of Integrated Project Delivery (IPD) in the Middle East: Implementation and Challenges
Authors: Sherif Mohamed , Abotaleb Ibrahim , Alqahtani Fahad K.
Published: April 2022

The Integrated Project Delivery method (IPD) is a contractual framework that features enhanced collaboration, risk and reward sharing under a single contract among the major project parties. This delivery method is gaining popularity in the US and other parts of the world, due to its proven results in efficient risk and cost sharing. Despite that, no significant investigations have been made to address the adaptability of the Middle East construction sector to the IPD delivery system. The objective of this research is to investigate the level of preparedness Middle Eastern markets have for adoption of the IPD delivery system. First, a thorough literature review was carried out to identify common barriers and enablers of applying IPD in construction. Second, a survey was carried out to assess and rank such barriers and enablers as they specifically apply to the Middle East construction sector. Third, through structured interviews with contract experts, strategies and guidelines were devised to be used by Middle East owners, consultants, and contractors who have the intention to implement the IPD delivery method in their projects. Finally, a thorough comparison was made between two major Middle Eastern countries, Egypt and the Kingdom of Saudi Arabia (KSA), in terms of IPD application. The findings reveal that the main barriers to implementing IPD stem from cultural resistance to the new system and lack of knowledge about it. The subsequent strategies outlined by the research are expected to help the construction industry in the Middle East gain more depth of knowledge about the benefits and application of IPD.
Investigation of the Thermal Performance of Lightweight Assembled Exterior Wall Panel (LAEWP) with Stud Connections
Authors: Li Tianzhen , Xia Jun , Chin Chee Seong , Song Pei
Published: April 2022

One of the most effective ways to improve building energy efficiency and consumption is to increase the thermal insulation of the building envelope and reduce the heat loss through walls. A new type of thermal insulation wall panel, consisting of a lightweight assembled exterior wall panel, was investigated in this research through experimental and numerical analyses. The feasibility of achieving the anticipated thermal performance through finite element modeling using ABAQUS® was verified. Good agreement between numerical simulation and experimental measurement was found, and the accuracy is 98.8%. To further reduce the heat transfer coefficient (U-value) of the panel to improve its thermal performance, parametric analyses were conducted utilizing the validated finite element model. The simulation shows that changing the insulation material is the best option, and the U-value reduction percentage reached 13.2%. Moreover, the combination of reducing the number of steel studs, decreasing the size of steel studs, implementing the opening of the light-gauge steel, and improving the insulation material led to a 23.7% reduction in the U-value at 0.695 W·m−2·K−1.
Expression of CD39 Identifies Activated Intratumoral CD8+ T Cells in Mismatch Repair Deficient Endometrial Cancer
Authors: Lubbers Joyce M. , Ważyńska Marta A. , van Rooij Nienke , Kol Arjan , Workel Hagma H. , Plat Annechien , Paijens Sterre T. , Vlaming Martijn R. , Spierings Diana C. J. , Elsinga Philip H. , Bremer Edwin , Nijman Hans W. , de Bruyn Marco
Published: April 2022

Identification of human cancer-reactive CD8+ T cells is crucial for the stratification of patients for immunotherapy and determination of immune-therapeutic effects. To date, these T cells have been identified mainly based on cell surface expression of programmed cell death protein 1 (PD-1) or co-expression of CD103 and CD39. A small subset of CD103− CD39+ CD8+ T cells is also present in tumors, but little is known about these T cells. Here, we report that CD103− CD39+ CD8+ T cells from mismatch repair-deficient endometrial tumors are activated and characterized predominantly by expression of TNFRSF9. In vitro, transforming growth factor-beta (TGF-β) drives the disappearance of this subset, likely through the conversion of CD103− CD39+ cells to a CD103+ phenotype. On the transcriptomic level, T cell activation and induction of CD39 was associated with a number of tissue residence and TGF-β responsive transcription factors. Altogether, our data suggest CD39+ CD103− CD8+ tumor-infiltrating T cells are recently activated and likely rapidly differentiate towards tissue residence upon exposure to TGF-β in the tumor micro-environment, explaining their relative paucity in human tumors.
Targeted Transposition of Minicircle DNA Using Single-Chain Antibody Conjugated Cyclodextrin-Modified Poly (Propylene Imine) Nanocarriers
Authors: Jugel Willi , Tietze Stefanie , Daeg Jennifer , Appelhans Dietmar , Broghammer Felix , Aigner Achim , Karimov Michael , Schackert Gabriele , Temme Achim
Published: April 2022

Among non-viral vectors, cationic polymers, such as poly(propylene imine) (PPI), play a prominent role in nucleic acid delivery. However, limitations of polycationic polymer-based DNA delivery systems are (i) insufficient target specificity, (ii) unsatisfactory transgene expression, and (iii) undesired transfer of therapeutic DNA into non-target cells. We developed single-chain antibody fragment (scFv)-directed hybrid polyplexes for targeted gene therapy of prostate stem cell antigen (PSCA)-positive tumors. Besides mono-biotinylated PSCA-specific single-chain antibodies (scFv(AM1-P-BAP)) conjugated to neutravidin, the hybrid polyplexes comprise β-cyclodextrin-modified PPI as well as biotin/maltose-modified PPI as carriers for minicircle DNAs encoding for Sleeping Beauty transposase and a transposon encoding the gene of interest. The PSCA-specific hybrid polyplexes efficiently delivered a GFP gene in PSCA-positive tumor cells, whereas control hybrid polyplexes showed low gene transfer efficiency. In an experimental gene therapy approach, targeted transposition of a codon-optimized p53 into p53-deficient HCT116p53−/−/PSCA cells demonstrated decreased clonogenic survival when compared to mock controls. Noteworthily, p53 transposition in PTEN-deficient H4PSCA glioma cells caused nearly complete loss of clonogenic survival. These results demonstrate the feasibility of combining tumor-targeting hybrid polyplexes and Sleeping Beauty gene transposition, which, due to the modular design, can be extended to other target genes and tumor entities.
Sulfur Exafluoride Contrast-Enhanced Ultrasound Showing Early Wash-Out of Marked Degree Identifies Lymphoma Invasion of Spleen with Excellent Diagnostic Accuracy: A Monocentric Study of 260 Splenic Nodules
Authors: Picardi Marco , Giordano Claudia , Trastulli Fabio , Leone Aldo , Della Pepa Roberta , Pugliese Novella , Iula Rossella , Delle Cave Giuseppe , Rascato Maria Gabriella , Esposito Maria , Vigliar Elena , Troncone Giancarlo , Mascolo Massimo , Russo Daniela , Persico Marcello , Pane Fabrizio
Published: April 2022

Contrast-enhanced ultrasonography (CEUS) use for detecting lymphoma in the spleen was questioned because of the risk of its inadequate diagnostic accuracy. The aim of the present study was to validate CEUS exam for the identification of spleen involvement by lymphoma in patients at risk. A total of 260 nodules from the spleens of 77 patients with lymph node biopsy-proven non-Hodgkin lymphoma (NHL; n = 44) or Hodgkin lymphoma (HL; n = 33) at staging (n = 56) or follow-up (n = 21) were collected in a hematology Italian center and retrospectively analyzed. Nodules were classified as malignant lymphoma if ≥0.5 cm (long axis) with arterial phase isoen-hancement and early (onset <60 s after contrast agent injection) wash-out of marked (≤120 s after contrast agent injection) degree. Other perfusional combinations at CEUS scans qualified lesions as benign or inconclusive. Diagnostic reference standard was clinical laboratory imaging monitoring for 230 nodules, and/or histology for 30 nodules. The median nodule size was 1.5 cm (range 0.5–7 cm). According to the reference standard, 204 (78%) nodules were lymphomas (aggressive-NHL (a-NHL), 122; classic-HL (c-HL), 65; indolent (i)-NHL, 17) and 56 (22%) were benign (inflammation, infection, and/or mesenchymal) lesions. Sensitivity, specificity, positive predictive value, negative predictive value, and overall diagnostic accuracy of CEUS for detecting lymphoma in the spleen were 95%, 100%, 100%, 85%, and 96%, respectively. Marked wash-out range of 55–90 s (median, 74 s), 92–120 s (median, 100 s), and 101–120 s (median, 114.5 s) was 100%, 96.6%, and 77% predictive of a-NHL, c-HL, and i-NHL splenic nodular infiltration, respectively. The CEUS perfusional pattern of arterial phase isoenhancement with early wash-out of marked degree was highly accurate for the detection of lymphomatous invasion of spleen in patients at risk, enabling its use for a confident non-invasive diagnosis.
CD47-SIRPα Checkpoint Disruption in Metastases Requires Tumor-Targeting Antibody for Molecular and Engineered Macrophage Therapies
Authors: Andrechak Jason C. , Dooling Lawrence J. , Tobin Michael P. , Zhang William , Hayes Brandon H. , Lee Justine Y. , Jin Xiaoling , Irianto Jerome , Discher Dennis E.
Published: April 2022

The macrophage checkpoint interaction CD47-SIRPα is an emerging target for cancer therapy, but clinical trials of monoclonal anti-CD47 show efficacy only in liquid tumors when combined with tumor-opsonizing IgG. Here, in challenging metastatic solid tumors, CD47 deletion shows no effect on tumor growth unless combined with otherwise ineffective tumor-opsonization, and we likewise show wild-type metastases are suppressed by SIRPα-blocked macrophages plus tumor-opsonization. Lung tumor nodules of syngeneic B16F10 melanoma cells with CD47 deletion show opsonization drives macrophage phagocytosis of B16F10s, consistent with growth versus phagocytosis calculus for exponential suppression of cancer. Wild-type CD47 levels on metastases in lungs of immunocompetent mice and on human metastases in livers of immunodeficient mice show that systemic injection of antibody-engineered macrophages also suppresses growth. Such in vivo functionality can be modulated by particle pre-loading of the macrophages. Thus, even though CD47-SIRPα disruption and tumor-opsonizing IgG are separately ineffective against established metastatic solid tumors, their combination in molecular and cellular therapies prolongs survival.
Inactivation of Escherichia coli Using Biogenic Silver Nanoparticles and Ultraviolet (UV) Radiation in Water Disinfection Processes
Authors: Tasic Ljubica , Stanisic Danijela , Barros Caio H. N. , Covesi Letícia Khater , Bandala Erick R.
Published: April 2022

This work tested the antimicrobial activity of three different biogenic silver nanoparticles (AgNPs) against Escherichia coli (E. coli) for water disinfection processes. The influence of different AgNP capping or stabilizing agents (e.g., protein or carbohydrate capped) and the use of ultraviolet (UV) radiation on the disinfection process were also assessed. The use of UV radiation was found to enhance the antimicrobial effects of AgNPs on E. coli. The antibacterial effects of AgNPs depended on the type of the capping biomolecules. Protein-capped nanoparticles showed greater antimicrobial effects compared with carbohydrate-capped (cellulose nanofibers, CNF) nanoparticles. Those capped with the fungal secretome proteins were the most active in E. coli inactivation. The least E. coli inactivation was observed for CNF-capped AgNPs. The size of the tested AgNPs also showed an expected effect on their anti-E. coli activity, with the smallest particles being the most active. The antimicrobial effects of biogenic AgNPs on E. coli make them an effective, innovative, and eco-friendly alternative for water disinfection processes, which supports further research into their use in developing sustainable water treatment processes.
Fabrication of Stable Cu-Ce Catalyst with Active Interfacial Sites for NOx Elimination by Flame Spray Pyrolysis
Authors: Tong Xin , Yu Jiafeng , Zhang Ling , Sun Jian
Published: April 2022

The complete conversion of NOx to harmless N2 without N2O formation is crucial for the control of air pollution, especially at low temperatures. Cu-based catalysts are promising materials due to their low cost and high activity in NO dissociation, even comparable to noble metals; however, they suffer from low stability. Here, we established a Cu-Ce catalyst in one step with strong metal–support interaction by the flame spray pyrolysis (FSP) method. Almost 100% NO conversion was achieved at 100 °C, and they completely transferred into N2 at a low temperature (200 °C) for the FSP-CuCe catalyst, exhibiting excellent performance in NO reduction by CO reaction. Moreover, the catalytic performance can stay stable, while 23% NO conversion was lost in the same condition for the one made by the co-precipitation (CP) method. This can be attributed to the synergistic effect of abundant active interfacial sites and more flexible surface oxygen created during the FSP process. The flame technology developed here provides an efficient way to fabricate strong metal–support interactions, exhibiting notable potential in the design of stable Cu-based catalysts.
Correction: Tsimbalyuk et al. The Intrinsically Disordered W Protein Is Multifunctional during Henipavirus Infection, Disrupting Host Signalling Pathways and Nuclear Import. Cells 2020, 9, 1913
Authors: Tsimbalyuk Sofiya , Cross Emily M. , Hoad Mikayla , Donnelly Camilla M. , Roby Justin A. , Forwood Jade K.
Published: April 2022

The authors would like to make the following corrections to the published paper [...]
Continuous Percoll Gradient Centrifugation of Erythrocytes—Explanation of Cellular Bands and Compromised Age Separation
Authors: Maurer Felix , John Thomas , Makhro Asya , Bogdanova Anna , Minetti Giampaolo , Wagner Christian , Kaestner Lars
Published: April 2022

(1) Background: When red blood cells are centrifuged in a continuous Percoll-based density gradient, they form discrete bands. While this is a popular approach for red blood cell age separation, the mechanisms involved in banding were unknown. (2) Methods: Percoll centrifugations of red blood cells were performed under various experimental conditions and the resulting distributions analyzed. The age of the red blood cells was measured by determining the protein band 4.1a to 4.1b ratio based on western blots. Red blood cell aggregates, so-called rouleaux, were monitored microscopically. A mathematical model for the centrifugation process was developed. (3) Results: The red blood cell band pattern is reproducible but re-centrifugation of sub-bands reveals a new set of bands. This is caused by red blood cell aggregation. Based on the aggregation, our mathematical model predicts the band formation. Suppression of red blood cell aggregation reduces the band formation. (4) Conclusions: The red blood cell band formation in continuous Percoll density gradients could be explained physically by red blood cell aggregate formation. This aggregate formation distorts the density-based red blood cell age separation. Suppressing aggregation by osmotic swelling has a more severe effect on compromising the RBC age separation to a higher degree.
Target Hopping from Protein Kinases to PXR: Identification of Small-Molecule Protein Kinase Inhibitors as Selective Modulators of Pregnane X Receptor from TüKIC Library
Authors: Mustonen Enni-Kaisa , Pantsar Tatu , Rashidian Azam , Reiner Juliander , Schwab Matthias , Laufer Stefan , Burk Oliver
Published: April 2022

Small-molecule protein kinase inhibitors are used for the treatment of cancer, but off-target effects hinder their clinical use. Especially off-target activation of the pregnane X receptor (PXR) has to be considered, as it not only governs drug metabolism and elimination, but also can promote tumor growth and cancer drug resistance. Consequently, PXR antagonism has been proposed for improving cancer drug therapy. Here we aimed to identify small-molecule kinase inhibitors of the Tübingen Kinase Inhibitor Collection (TüKIC) compound library that would act also as PXR antagonists. By a combination of in silico screen and confirmatory cellular reporter gene assays, we identified four novel PXR antagonists and a structurally related agonist with a common phenylaminobenzosuberone scaffold. Further characterization using biochemical ligand binding and cellular protein interaction assays classified the novel compounds as mixed competitive/noncompetitive, passive antagonists, which bind PXR directly and disrupt its interaction with coregulatory proteins. Expression analysis of prototypical PXR target genes ABCB1 and CYP3A4 in LS174T colorectal cancer cells and HepaRG hepatocytes revealed novel antagonists as selective receptor modulators, which showed gene- and tissue-specific effects. These results demonstrate the possibility of dual PXR and protein kinase inhibitors, which might represent added value in cancer therapy.
Application of Multiharmonic QCM-D for Detection of Plasmin at Hydrophobic Surfaces Modified by β-Casein
Authors: Spagnolo Sandro , Muckley Eric S. , Ivanov Ilia N. , Hianik Tibor
Published: April 2022

Plasmin protease plays an important role in many processes in living systems, including milk. Monitoring plasmin activity is important for control of the nutritional quality of milk and other dairy products. We designed a biosensor to detect the proteolytic activity of plasmin, using multiharmonic quartz crystal microbalance with dissipation (QCM-D). The β-casein immobilized on the hydrophobic surface of 1-dodecanethiol on the AT-cut quartz crystal was used to monitor plasmin activity. We demonstrated detection of plasmin in a concentration range of 0.1–20 nM, with the limit of detection about 0.13 ± 0.01 nM. The analysis of viscoelastic properties of the β-casein layer showed rapid changes of shear elasticity modulus, μ, and coefficient of viscosity, η, at plasmin sub-nanomolar concentrations, followed by modest changes at nanomolar concentrations, indicating multilayer architecture β-casein. A comparative analysis of viscoelastic properties of β-casein layers following plasmin and trypsin cleavage showed that the higher effect of trypsin was due to larger potential cleavage sites of β-casein.
Second and Third Generational Advances in Therapies of the Immune-Mediated Kidney Diseases in Children and Adolescents
Authors: Grenda Ryszard , Obrycki Łukasz
Published: April 2022

Therapy of immune-mediated kidney diseases has evolved during recent decades from the non-specific use of corticosteroids and antiproliferative agents (like cyclophosphamide or azathioprine), towards the use of more specific drugs with measurable pharmacokinetics, like calcineurin inhibitors (cyclosporine A and tacrolimus) and mycophenolate mofetil, to the treatment with biologic drugs targeting detailed specific receptors, like rituximab, eculizumab or abatacept. Moreover, the data coming from a molecular science revealed that several drugs, which have been previously used exclusively to modify the upregulated adaptive immune system, may also exert a local effect on the kidney microstructure and ameliorate the functional instability of podocytes, reducing the leak of protein into the urinary space. The innate immune system also became a target of new therapies, as its specific role in different kidney diseases has been de novo defined. Current therapy of several immune kidney diseases may now be personalized, based on the detailed diagnostic procedures, including molecular tests. However, in most cases there is still a space for standard therapies based on variable protocols including usage of steroids with the steroid-sparing agents. They are used as a first-line treatment, while modern biologic agents are selected as further steps in cases of lack of the efficacy or toxicity of the basic therapies. In several clinical settings, the biologic drugs are effective as the add-on therapy.
Suicide Prevention Program with Cooperation from Senior Volunteers, Governments, and Schools: A Study of the Intervention Effects of “Educational Lessons Regarding SOS Output” Focusing on Junior High School Students
Authors: Ogawa Susumu , Suzuki Hiroyuki , Takahashi Tomoya , Fujita Koji , Murayama Yoh , Sato Kenichiro , Matsunaga Hiroko , Motohashi Yutaka , Fujiwara Yoshinori
Published: April 2022

As a suicide countermeasure for young people, implementing “SOS output education” that provides young people with opportunities and approaches to seeking support with community cooperation can be expected to reduce lifelong suicide risk. We implemented an “SOS output education” for junior high school students with cooperation from educators, government staff, and older people working as community volunteers. A total of 188 students were allocated to an intervention group and a waiting group. Outcome assessments were implemented at three points in time: before the program (Time 1), after the program (Time 2), and three months after the program (Time 3). Results showed that the number of people with worries increased in the intervention group compared with the waiting group between Time 1 and Time 2. There was also an increase in people with “reliable adults” between Time 1 and Time 3, and people with “adults who you can talk to at any time” increased between Time 2 and Time 3 in the intervention group. By implementing the SOS output education program with community cooperation, an increase was observed in the intervention group in terms of support-seeking awareness and the number of people with reliable adults and with adults who they can talk to at any time.
Self-Harm, Suicidal Ideation and Attempts among School-Attending Adolescents in Bamako, Mali
Authors: Yedong Wu , Coulibaly Souleymane Papa , Sidibe Aissata Mahamadou , Hesketh Thérèse
Published: April 2022

Suicide and self-harm are major public health concerns for adolescents globally, but there is a dearth of related research in West Africa. This study aims to examine the prevalence and associated factors for self-harm, suicidal ideation and suicide attempts among adolescents in the West African country of Mali. A questionnaire survey was conducted among adolescents attending school or university in August 2019 in Bamako, the capital of Mali. Logistical constraints necessitated convenience sampling. Outcome measures were self-harm and suicide ideation and attempts. Predictor variables included sociodemographic characteristics, bullying and mental health problems. There were 606 respondents who completed questionnaires; their mean age was 16.1 (SD = 2.4); 318 (52.5%) were identified as male; and 44.4% reported self-harm at some point in their life, with 21% reporting suicide ideation and 9.7% actual suicide attempts. For all three outcomes, older age, knowing somebody personally who had experienced self-harm or taken their own life, moderate to severe depression or anxiety, and being a victim of bullying were highly significant risk factors for self-harm, suicidal ideation and suicide attempts in these adolescents, while high self-esteem decreased the risk. The study suggests that self-harm and suicidal behaviour are relatively common in Malian adolescents who are still in education. However, much more research is needed to better understand this phenomenon.
New Insights into Evolution of the ABC Transporter Family in Mesostigma viride, a Unicellular Charophyte Algae
Authors: Gong Xiaoping , Wang Shanhong
Published: April 2022

ATP-binding cassette (ABC) transporters play an important role in driving the exchange of multiple molecules across cell membranes. The plant ABC transporter family is among the largest protein families, and recent progress has advanced our understanding of ABC classification. However, the ancestral form and deep origin of plant ABCs remain elusive. In this study, we identified 59 ABC transporters in Mesostigma viride, a unicellular charophyte algae that represents the earliest diverging lineage of streptophytes, and 1034 ABCs in genomes representing a broad taxonomic sampling from distantly related plant evolutionary lineages, including chlorophytes, charophytes, bryophytes, lycophytes, gymnosperms, basal angiosperms, monocots, and eudicots. We classified the plant ABC transporters by comprehensive phylogenetic analysis of each subfamily. Our analysis revealed the ancestral type of ABC proteins as well as duplication and gene loss during plant evolution, contributing to our understanding of the functional conservation and diversity of this family. In summary, this study provides new insight into the origin and evolution of plant ABC transporters.
Comment on Aldén et al. Intracellular Reverse Transcription of Pfizer BioNTech COVID-19 mRNA Vaccine BNT162b2 In Vitro in Human Liver Cell Line. Curr. Issues Mol. Biol. 2022, 44, 1115–1126
Authors: Merchant Hamid A.
Published: April 2022

Aldén et al. (2022) recently reported the intracellular reverse transcription of Pfizer BioNTech COVID-19 mRNA Vaccine BNT162b2 in vitro in a human liver cell line (Huh7) [...]
The Direct and Oblique Shear Bond Strength of Geogrid-Reinforced Asphalt
Authors: Li Qiaoyi , Yang Guangqing , Wang He , Yue Zhijie
Published: April 2022

The interlayer bonding strength is an essential property of geogrid-reinforced asphalt. To study the interlayer bonding characteristics of geogrid-reinforced asphalt, direct shear and oblique shear tests were carried out in the laboratory. The direct interlaminar shear strength of geogrid-reinforced asphalt was lower than that of unreinforced asphalt. The oblique shear strength of the carbon–carbon geogrid-reinforced sample was the highest, the unreinforced sample was second, and the carbon–glass geogrid-reinforced sample was the lowest. The stiffness of the geogrid affects the oblique shear strength. The interlayer direct shear strengths of AC-20C asphalt samples were higher than AC-13C asphalt samples. The oblique shear strengths of AC-20C asphalt samples were almost the same as the AC-13C asphalt samples. Normal stress made the double-layered sample tend to behave as a homogeneous granular material. The direct shear strength vs. shear displacement curves showed an area of oscillation, but the oblique shear curves were smooth throughout the process.
Co-Design of the Control and Power Stages of a Boost-Based Rectifier with Power Factor Correction Depending on Performance Criteria
Authors: Ramos-Paja Carlos Andres , Saavedra-Montes Andres Julian , Bastidas-Rodriguez Juan David
Published: April 2022

Rectifiers with power factor correction are key devices to supply DC loads from AC sources, guaranteeing a power factor close to one and low total harmonic distortion. Boost-based power factor correction rectifiers are the most widely used topology and they are formed by a power stage (diode bridge and Boost converter) and a control system. However, there is a relevant control problem, because controllers are designed with linearized models of the converters for a specific operating point; consequently, the required dynamic performance and stability of the whole system for different operating points are not guaranteed. Another weak and common practice is to design the power and control stages independently. This paper proposes a co-design procedure for both the power stage and the control system of a Boost-based PFC rectifier, which is focused on guaranteeing the system’s stability in any operating conditions. Moreover, the design procedure assures a maximum switching frequency and the fulfillment of different design requirements for the output voltage: maximum overshoot and settling time before load disturbances, maximum ripple, and the desired damping ratio. The proposed control has a cascade structure, where the inner loop is a sliding-mode controller (SMC) to track the inductor current reference, and the outer loop is an adaptive PI regulator of the output voltage, which manipulates the amplitude of the inductor current reference. The paper includes the stability analysis of the SMC, the design procedure of the inductor to guarantee the system stability, and the design of the adaptive PI controller parameters and the capacitor to achieve the desired dynamic performance of the output voltage. The proposed rectifier is simulated in PSIM and the results validate the co-design procedures and show that the proposed system is stable for any operating conditions and satisfies the design requirements.
Study of High Polarized Nanostructure Light-Emitting Diode
Authors: Chu Kuo-Hsiung , Chen Jo-Hsiang , Hong Kuo-Bin , Huang Yu-Ming , Chiu Shih-Wen , Ke Fu-Yao , Sun Chia-Wei , Kao Tsung-Sheng , Sher Chin-Wei , Kuo Hao-Chung
Published: April 2022

In this study, we investigated the characteristic difference between the two different configurations of the three-dimensional shell–core nanorod LED. We achieve a degree of polarization of 0.545 for tip-free core–shell nanorod LED and 0.188 for tip core–shell nanorod LED by combining the three-dimensional (3D) structure LED with photonic crystal. The ability of low symmetric modes generated by photonic crystals to enhance degree of polarization has been demonstrated through simulations of photonic crystals. In addition, light confinement in GaN-based nanorod structures is induced by total internal reflection at the GaN/air interface. The combination of 3D core–shell nanorod LED and photonic crystals cannot only produce a light source with a high degree of polarization, but also a narrow divergence angle up to 56°. These 3D LEDs may pave the way for future novel optoelectronic components.
Holocene Genetic Evolution of Pig (Sus scrofa) on Romanian Territory in a European Time and Space Frame
Authors: Stanc Margareta Simina , Luca Monica , Bălășescu Adrian , Bejenaru Luminița
Published: April 2022

Romanian territory represents a key point in the dispersal of domestic pigs into Europe, due to its geographical position. Our study gathers a high number of samples from different archaeological sites on Romanian territory in order to establish a more accurate chronological view of the spread of domestic pig into Europe and to investigate the possibility of a local domestication process. Approximately 200 samples from 45 archaeological sites on Romanian territory, covering a large period of time, from the Neolithic to the Middle Ages, were subjected to DNA analysis. The sequencing of a short fragment from the D-loop region of the mitochondrial DNA identified a different prevalence of domestic pig genetic signature between two periods of time: the Neolithic period and the Early Bronze Age–Middle Ages period. While the Neolithic period is characterized by the presence of domestic pigs with a Near-Eastern signature, during the Early Bronze Age–Middle Ages period this genetic signature is replaced with a European one. Two European and two Near-Eastern signatures were described for all the analysed samples, each of them prevailing within the wild, respectively domestic Sus scrofa. The data also revealed the introgression process as a form of domestication in Romanian territory.
Integrative Taxonomy Supports Two New Species of Rhodiola (Crassulaceae) in Xizang, China
Authors: Meng Shiyong , Wang Zimeng , Ye Lv
Published: April 2022

The Qinghai–Tibet Plateau includes the Himalayas and Hengduan Mountains and is well known for its rich biodiversity. Evolutionary radiation is one of the main ways by which plants diversify in mountains, particularly the Qinghai–Tibet Plateau. It presents a large challenge to the classification of taxa that radiate quickly. One way to overcome these challenges is to continue conducting detailed field studies while integrating morphological and molecular evidence to classify these taxa. The aim of this research was to provide a case for the systematic study of the complex taxa Rhodiola, which rapidly radiate. During the field study, we found two unique variants of Rhodiola in an alpine dry meadow and beds of pebbles on beaches, respectively. We utilized a morphological principal component analysis, scanning electron microscopy and molecular phylogenetic analysis to propose two new species: Rhodiola wangii S.Y. Meng and Rhodiola namlingensis S.Y. Meng. R. wangii is similar to R. stapfii (Hamet) S.H. Fu, but it differs in having an intensely broad rhombus and alternate leaves, a distinct petiole, stamens gathered together and reflexed purple scales. R. namlingensis is similar to R. prainii (Hamet) H. Ohba, but it differs in its exerted alternate leaves, the presence of more than four leaves on the stem, thick leaf blades, an obovate to inverted triangle, and short petioles. The conservation status of these two species was also assessed.
One on Top of the Other: Exploring the Habitat Cascades Phenomenon in Iconic Biogenic Marine Habitats
Authors: Kazanidis Georgios , Guido Adriano , Rosso Antonietta , Sanfilippo Rossana , Roberts J. Murray , Gerovasileiou Vasilis
Published: April 2022

Biogenic habitats often form hot spots of biodiversity. However, the role of epibiosis and the ‘habitat cascades’ phenomenon in enhancing structural heterogeneity and biodiversity in biogenic habitats in remote and difficult-to-access areas is little known. In this work, we provide the first insight by exploring epibiosis across remote habitats that often support high levels of biodiversity, i.e., cold-water coral reefs and marine caves. The present study acts as a stepping-stone for the further exploration of ‘habitat cascades’ in habitats where scientific knowledge about this phenomenon is limited.
Valorization of Concentrated Dairy White Wastewater by Reverse Osmosis in Model Cheese Production
Authors: Alalam Sabine , Chamberland Julien , Gravel Alexia , Perreault Véronique , Britten Michel , Pouliot Yves , Labrie Steve , Doyen Alain
Published: April 2022

Treatment of dairy white wastewater (WW) by reverse osmosis (RO) is usually performed to generate process water and to reclaim dairy components for their valorization. For this study, a mixture of pasteurized milk and WW from a dairy plant was concentrated by RO to achieve a protein concentration similar to that of skimmed milk. Retentates, which are concentrated WW, were used in the preparation of cheese milk. The effect of using model concentrated WW was evaluated on (1) the soluble–colloidal equilibrium between protein and salt, (2) the milk-coagulation kinetics, and (3) the cheese composition and yield. An economic assessment was also carried out to support the decision-making process for implementing a new RO system in a dairy plant for the valorization of dairy WW. The results showed that substituting more than 50% of the amount of cheese milk with model pasteurized WW concentrates decreased the moisture-adjusted cheese yield and impaired the coagulation kinetics. Excessive cheese moisture was observed in cheeses that were made from 50% and 100% model WW concentrates, correlating with a change in the soluble–colloidal equilibrium of salts, especially in calcium. To achieve sustainable and economic benefits, the ratio of added WW concentrates to cheese milk must be less than 50%. However, for such an investment to be profitable to a dairy plant within 0.54 years, a large-size plant must generate 200 m3 of WW per day with at least 0.5% of total solids, as the economic analysis specific to our case suggests.
Fasting during Ramadan: A Comprehensive Review for Primary Care Providers
Authors: Ahmed Sumera , Khokhar Natasha , Shubrook Jay H.
Published: April 2022

Diabetes mellitus has become a non-infectious pandemic. The incidence of T2D has risen dramatically and recent rates have increased in many countries including Muslim countries. As the number of people who participate in Ramadan increases, health care professionals will need to become familiar with the traditions and help people stay healthy during the holy month of Ramadan. A key part of Ramadan is the practice of one month of fasting from sunrise to sunset. While this is a religious practice, it has significant impacts on the management of people with diabetes. This article will discuss the traditions associated with Ramadan and how to help people safely manage their diabetes while participating in Ramadan.
Motor Imagery: How to Assess, Improve Its Performance, and Apply It for Psychosis Diagnostics
Authors: Chepurova Alla , Hramov Alexander , Kurkin Semen
Published: April 2022

With this review, we summarize the state-of-the-art of scientific studies in the field of motor imagery (MI) and motor execution (ME). We composed the brain map and description that correlate different brain areas with the type of movements it is responsible for. That gives a more complete and systematic picture of human brain functionality in the case of ME and MI. We systematized the most popular methods for assessing the quality of MI performance and discussed their advantages and disadvantages. We also reviewed the main directions for the use of transcranial magnetic stimulation (TMS) in MI research and considered the principal effects of TMS on MI performance. In addition, we discuss the main applications of MI, emphasizing its use in the diagnostics of various neurodegenerative disorders and psychoses. Finally, we discuss the research gap and possible improvements for further research in the field.