bluuebunny/crossref_metadata_2025 huggingface dataset:
Early Transcriptional Liver Signatures in Experimental Visceral Leishmaniasis
Authors: Palacios Génesis , Diaz-Solano Raquel , Valladares Basilio , Dorta-Guerra Roberto , Carmelo Emma
Published: July 2021

Transcriptional analysis of complex biological scenarios has been used extensively, even though sometimes the results of such analysis may prove imprecise or difficult to interpret due to an overwhelming amount of information. In this study, a large-scale real-time qPCR experiment was coupled to multivariate statistical analysis in order to describe the main immunological events underlying the early L. infantum infection in livers of BALB/c mice. High-throughput qPCR was used to evaluate the expression of 223 genes related to immunological response and metabolism 1, 3, 5, and 10 days post infection. This integrative analysis showed strikingly different gene signatures at 1 and 10 days post infection, revealing the progression of infection in the experimental model based on the upregulation of particular immunological response patterns and mediators. The gene signature 1 day post infection was not only characterized by the upregulation of mediators involved in interferon signaling and cell chemotaxis, but also the upregulation of some inhibitory markers. In contrast, at 10 days post infection, the upregulation of many inflammatory and Th1 markers characterized a more defined gene signature with the upregulation of mediators in the IL-12 signaling pathway. Our results reveal a significant connection between the expression of innate immune response and metabolic and inhibitory markers in early L. infantum infection of the liver.
Antiepileptic Stiripentol May Influence Bones
Authors: Matuszewska Agnieszka , Nowak Beata , Nikodem Anna , Merwid-Ląd Anna , Wiatrak Benita , Tomkalski Tomasz , Jędrzejuk Diana , Szeląg Ewa , Sozański Tomasz , Danielewski Maciej , Jawień Paulina , Ceremuga Ireneusz , Szandruk-Bender Marta , Bolanowski Marek , Filipiak Jarosław , Szeląg Adam
Published: July 2021

Bone structure abnormalities are increasingly observed in patients chronically treated with antiepileptic drugs (AEDs). The majority of the available data concern older conventional AEDs, while the amount of information regarding newer AEDs, including stiripentol, is limited. The aim of the study was to assess the effect of stiripentol on bones. For 24 weeks, male Wistar rats, received 0.9% sodium chloride (control group) or stiripentol (200 mg/kg/day) (STP group). In the 16th week of the study, we detected lower serum PINP levels in the STP group compared to the control group. In the 24th week, a statistically significant lower 1,25-dihydroxyvitamin D3 level, higher inorganic phosphate level and higher neutrophil gelatinase-associated lipocalin (NGAL) levels in serum were found in the STP group compared to the control. Micro X-ray computed tomography of the tibias demonstrated lower bone volume fraction, lower trabecular thickness, higher trabecular pattern factor and a higher structure model index in the stiripentol group. Considering the results of this experiment on rats which suggests that long-term administration of stiripentol may impair the cancellous bone microarchitecture, further prospective human studies seem to be justified. However, monitoring plasma vitamin D, calcium, inorganic phosphate and kidney function in patients on long-term stiripentol therapy may be suggested.
B Cell Adhesion to Fibroblast-Like Synoviocytes Is Up-Regulated by Tumor Necrosis Factor-Alpha via Expression of Human Vascular Cell Adhesion Molecule-1 Mediated by B Cell-Activating Factor
Authors: Yoon Sung-Sik , Moon Eun-Yi
Published: July 2021

Fibroblast-like synoviocytes (FLSs) play a key role in the pathogenesis of rheumatoid arthritis (RA) by producing inflammatory cytokines and interacting with various immune cells, which contribute to cartilage destruction. RA-FLSs activated by tumor necrosis factor alpha (TNF-α), exacerbate joint damage by triggering the expression of various inflammatory molecules, including human vascular cell adhesion molecule-1 (hVCAM1) and B cell-activating factor (hBAFF), with a role in maturation and maintenance of B cells. Here, we investigated whether B cell interaction with FLSs could be associated with hVCAM1 expression by TNF-α through hBAFF, using WiL2-NS B cells and MH7A synovial cells. TNF-α enhanced the expression of hVCAM1 and hBAFF. B cell adhesion to FLSs was increased by treatment with TNF-α or hBAFF protein. hVCAM expression was up-regulated by transcriptional activation of the hVCAM1 promoter(−1549 to −54) in MH7A cells treated with hBAFF protein or overexpressed with hBAFF gene. In contrast, hVCAM1 expression was down-regulated by treatment with hBAFF-siRNA. JNK was activated by TNF-α treatment. Then, hVCAM1 expression and B cell adhesion to FLSs were reduced by the treatment with JNK inhibitor SP600125. Transcriptional activity of hVCAM1 by the stimulation with TNF-α was inhibited by the deletion of −1549 to −229 from the hVCAM1 promoter. hVCAM1 expression and B cell adhesion to FLSs were reduced by treatment with hVCAM1-siRNA. Taken together, these results suggest that B cell adhesion to FLSs is associated with TNF-α-induced up-regulation of hVCAM1 expression via hBAFF expression. Thus, the pathological progression of RA may be associated with hVCAM1-mediated interaction of synovial cells with B lymphocytes.
Gibberellin Oxidase Gene Family in L. chinense: Genome-Wide Identification and Gene Expression Analysis
Authors: Hu Lingfeng , Wang Pengkai , Hao Zhaodong , Lu Ye , Xue Guoxia , Cao Zijian , Qu Haoxian , Cheng Tielong , Shi Jisen , Chen Jinhui
Published: July 2021

GAox is a key enzyme for the transformation of gibberellins, and belongs to the 2-ketoglutarate dependent dioxygenase gene family (2ODD). However, a systematic analysis of GAox in the angiosperm L. chinense has not yet been reported. Here, we identified all LcGAox gene family members in L. chinense, which were classified into the three subgroups of GA20ox, C19GA2ox, and C20GA2ox. Comparison of the gene structure, conserve motifs, phylogenetic relationships, and syntenic relationships of gibberellin oxidase gene families in different species indicated that the gene functional differences may be due to the partial deletion of their domains during evolution. Furthermore, evidence for purifying selection was detected between orthologous GAox genes in rice, grape, Arabidopsis, and L. chinense. Analysis of the codon usage patterns showed that mutation pressure and natural selection might have induced codon usage bias in angiosperms; however, the LcGAox genes in mosses, lycophytes, and ambarella plants exhibited no obvious codon usage preference. These results suggested that the gibberellin oxidase genes were more primitive. The gene expression pattern was analyzed in different organs subjected to multiple abiotic stresses, including GA, abscisic acid (ABA), and chlormequat (CCC) treatment, by RNA-seq and qRT-PCR, and the stress- and phytohormone-responsive cis-elements were counted. The results showed that the synthesis and decomposition of GA were regulated by different LcGAox genes in the vegetative and reproductive organs of L. chinense, and only LcGA2ox1,4, and 7 responded to the NaCl, polyethylene glycol, 4 °C, GA, ABA, and CCC treatment in the roots, stems, and leaves of seedlings at different time periods, revealing the potential role of LcGAox in stress resistance.
Identification of the Merkel Cell Polyomavirus Large Tumor Antigen Ubiquitin Conjugation Residue
Authors: Ortiz Luz E. , Pham Alexander M. , Kwun Hyun Jin
Published: July 2021

Merkel cell polyomavirus (MCPyV) large tumor (LT) antigen is a DNA binding protein essential for viral gene transcription and genome replication. MCPyV LT interacts with multiple E3 ligases in a phosphorylation-dependent manner, limiting its own viral replication by enhancing LT protein degradation, which is a unique mechanism for MCPyV latency. Thus, identifying LT ubiquitination sites is an important step toward understanding the biological role of these virus-host interactions that can potentially result in viral oncogenesis. The ubiquitin (Ub) attachment sites in LT were predicted by using Rapid UBIquitination (RUBI), a sequence-based ubiquitination web server. Using an immunoprecipitation approach, the lysine (Lys, K) 585 residue in LT is identified as the ubiquitin conjugation site. Lysine 585 is deleted from tumor-derived truncated LTs (tLTs), resulting in stable expression of tLTs present in cancers. Substitution of lysine 585 to arginine (Arg, R) increased LT protein stability, but impaired MCPyV origin replication, due to a loss of ATP hydrolysis activity. These findings uncover a never-before-identified ubiquitination site of LT and its importance not only in the regulation of protein turnover, but also in MCPyV genome replication.
Product Distributions of Cytochrome P450 OleTJE with Phenyl-Substituted Fatty Acids: A Computational Study
Authors: Lin Yen-Ting , de Visser Sam P.
Published: July 2021

There are two types of cytochrome P450 enzymes in nature, namely, the monooxygenases and the peroxygenases. Both enzyme classes participate in substrate biodegradation or biosynthesis reactions in nature, but the P450 monooxygenases use dioxygen, while the peroxygenases take H2O2 in their catalytic cycle instead. By contrast to the P450 monooxygenases, the P450 peroxygenases do not require an external redox partner to deliver electrons during the catalytic cycle, and also no external proton source is needed. Therefore, they are fully self-sufficient, which affords them opportunities in biotechnological applications. One specific P450 peroxygenase, namely, P450 OleTJE, reacts with long-chain linear fatty acids through oxidative decarboxylation to form hydrocarbons and, as such, has been implicated as a suitable source for the biosynthesis of biofuels. Unfortunately, the reactions were shown to produce a considerable amount of side products originating from Cα and Cβ hydroxylation and desaturation. These product distributions were found to be strongly dependent on whether the substrate had substituents on the Cα and/or Cβ atoms. To understand the bifurcation pathways of substrate activation by P450 OleTJE leading to decarboxylation, Cα hydroxylation, Cβ hydroxylation and Cα−Cβ desaturation, we performed a computational study using 3-phenylpropionate and 2-phenylbutyrate as substrates. We set up large cluster models containing the heme, the substrate and the key features of the substrate binding pocket and calculated (using density functional theory) the pathways leading to the four possible products. This work predicts that the two substrates will react with different reaction rates due to accessibility differences of the substrates to the active oxidant, and, as a consequence, these two substrates will also generate different products. This work explains how the substrate binding pocket of P450 OleTJE guides a reaction to a chemoselectivity.
Music-Based Intervention Ameliorates Mecp2-Loss-Mediated Sociability Repression in Mice through the Prefrontal Cortex FNDC5/BDNF Pathway
Authors: Hung Pi-Lien , Wu Kay L. H. , Chen Chih-Jen , Siu Ka-Kit , Hsin Yi-Jung , Wang Liang-Jen , Wang Feng-Sheng
Published: July 2021

Patients with Rett syndrome (RTT) show severe difficulties with communication, social withdrawl, and learning. Music-based interventions improve social interaction, communication skills, eye contact, and physical skills and reduce seizure frequency in patients with RTT. This study aimed to investigate the mechanism by which music-based interventions compromise sociability impairments in mecp2 null/y mice as an experimental RTT model. Male mecp2 null/y mice and wild-type mice (24 days old) were randomly divided into control, noise, and music-based intervention groups. Mice were exposed to music or noise for 6 h/day for 3 consecutive weeks. Behavioral patterns, including anxiety, spontaneous exploration, and sociability, were characterized using open-field and three-chamber tests. BDNF, TrkB receptor motif, and FNDC5 expression in the prefrontal cortex (PFC), hippocampus, basal ganglia, and amygdala were probed using RT-PCR or immunoblotting. mecp2 null/y mice showed less locomotion in an open field than wild-type mice. The social novelty rather than the sociability of these animals increased following a music-based intervention, suggesting that music influenced the mecp2-deletion-induced social interaction repression rather than motor deficit. Mechanically, the loss of BDNF signaling in the prefrontal cortex and hippocampal regions, but not in the basal ganglia and amygdala, was compromised following the music-based intervention in mecp2 null/y mice, whereas TrkB signaling was not significantly changed in either region. FNDC5 expression in the prefrontal cortex region in mecp2 null/y mice also increased following the music-based intervention. Collective evidence reveals that music-based interventions improve mecp2-loss-induced social dysfunction. BDNF and FNDC5 signaling in the prefrontal cortex region mediates the music-based-intervention promotion of social interactions. This study gives new insight into the mechanisms underlying the improvement of social behaviors in mice suffering from experimental Rett syndrome following a music-based intervention.
Co-Adjuvant Therapy Efficacy of Catechin and Procyanidin B2 with Docetaxel on Hormone-Related Cancers In Vitro
Authors: Núñez-Iglesias Mª Jesús , Novio Silvia , García Carlota , Pérez-Muñuzuri Mª Elena , Martínez María-Carmen , Santiago José-Luis , Boso Susana , Gago Pilar , Freire-Garabal Manuel
Published: July 2021

Prostate (PC) and breast cancer (BC) are heterogeneous hormonal cancers. Treatment resistance and adverse effects are the main limitations of conventional chemotherapy treatment. The use of sensitizing agents could improve the effectiveness of chemotherapeutic drugs as well as obviate these limitations. This study analyzes the effect of single catechin (CAT), procyanidin B2 (ProB2) treatment as well as the co-adjuvant treatment of each of these compounds with docetaxel (DOCE). We used PC- and BC-derived cell lines (PC3, DU-145, T47D, MCF-7 and MDA-MB-231). The short and long-term pro-apoptotic, anti-proliferative and anti-migratory effects were analyzed. RT-qPCR was used to discover molecular bases of the therapeutic efficacy of these compounds. ProB2 treatment induced a two- to five-fold increase in anti-proliferative and pro-apoptotic effects compared to single DOCE treatment, and also had a more sensitizing effect than DOCE on DU145 cells. Regarding BC cells, ProB2- and CAT-mediated sensitization to DOCE anti-proliferative and pro-apoptotic effects was cell-independent and cell-dependent, respectively. Combined treatment led to high-efficacy effects on MCF-7 cells, which were associated to the up-regulation of CDKN1A, BAX, caspase 9 and E-cadherin mRNA under combined treatment compared to single DOCE treatment. CAT and ProB2 can enhance the efficacy of DOCE therapy on PC and BC cells by the sensitizing mechanism.
Evaluating the Effects of Subnormothermic Perfusion with AP39 in a Novel Blood-Free Model of Ex Vivo Kidney Preservation and Reperfusion
Authors: Juriasingani Smriti , Jackson Ashley , Zhang Max Yulin , Ruthirakanthan Aushanth , Dugbartey George J. , Sogutdelen Emrullah , Levine Max , Mandurah Moaath , Whiteman Matthew , Luke Patrick , Sener Alp
Published: July 2021

The use of blood for normothermic and subnormothermic kidney preservation hinders the translation of these approaches and promising therapeutics. This study evaluates whether adding hydrogen sulfide donor AP39 to Hemopure, a blood substitute, during subnormothermic perfusion improves kidney outcomes. After 30 min of renal pedicle clamping, porcine kidneys were treated to 4 h of static cold storage (SCS-4 °C) or subnormothermic perfusion at 21 °C with Hemopure (H-21 °C), Hemopure + 200 nM AP39 (H200nM-21 °C) or Hemopure + 1 µM AP39 (H1µM-21 °C). Then, kidneys were reperfused with Hemopure at 37 °C for 4 h with metabolic support. Perfusate composition, tissue oxygenation, urinalysis and histopathology were analyzed. During preservation, the H200nM-21 °C group exhibited significantly higher urine output than the other groups and significantly higher tissue oxygenation than the H1µM-21 °C group at 1 h and 2h. During reperfusion, the H200nM-21 °C group exhibited significantly higher urine output and lower urine protein than the other groups. Additionally, the H200nM-21 °C group exhibited higher perfusate pO2 levels than the other groups and significantly lower apoptotic injury than the H-21 °C and the H1µM-21 °C groups. Thus, subnormothermic perfusion at 21 °C with Hemopure + 200 nM AP39 improves renal outcomes. Additionally, our novel blood-free model of ex vivo kidney preservation and reperfusion could be useful for studying other therapeutics.
Effects of Venlafaxine, Risperidone and Febuxostat on Cuprizone-Induced Demyelination, Behavioral Deficits and Oxidative Stress
Authors: Mihai Dragos Paul , Ungurianu Anca , Ciotu Cosmin I. , Fischer Michael J. M. , Olaru Octavian Tudorel , Nitulescu George Mihai , Andrei Corina , Zbarcea Cristina Elena , Zanfirescu Anca , Seremet Oana Cristina , Chirita Cornel , Negres Simona
Published: July 2021

Multiple sclerosis (MS) is a demyelinating, autoimmune disease that affects a large number of young adults. Novel therapies for MS are needed considering the efficiency and safety limitations of current treatments. In our study, we investigated the effects of venlafaxine (antidepressant, serotonin-norepinephrine reuptake inhibitor), risperidone (atypical antipsychotic) and febuxostat (gout medication, xanthine oxidase inhibitor) in the cuprizone mouse model of acute demyelination, hypothesizing an antagonistic effect on TRPA1 calcium channels. Cuprizone and drugs were administered to C57BL6/J mice for five weeks and locomotor activity, motor performance and cold sensitivity were assessed. Mice brains were harvested for histological staining and assessment of oxidative stress markers. Febuxostat and metabolites of venlafaxine (desvenlafaxine) and risperidone (paliperidone) were tested for TRPA1 antagonistic activity. Following treatment, venlafaxine and risperidone significantly improved motor performance and sensitivity to a cold stimulus. All administered drugs ameliorated the cuprizone-induced deficit of superoxide dismutase activity. Desvenlafaxine and paliperidone showed no activity on TRPA1, while febuxostat exhibited agonistic activity at high concentrations. Our findings indicated that all three drugs offered some protection against the effects of cuprizone-induced demyelination. The agonistic activity of febuxostat can be of potential use for discovering novel TRPA1 ligands.
Mechanism of the Conformational Change of the Protein Methyltransferase SMYD3: A Molecular Dynamics Simulation Study
Authors: Sun Jixue , Li Zibin , Yang Na
Published: July 2021

SMYD3 is a SET-domain-containing methyltransferase that catalyzes the transfer of methyl groups onto lysine residues of substrate proteins. Methylation of MAP3K2 by SMYD3 has been implicated in Ras-driven tumorigenesis, which makes SMYD3 a potential target for cancer therapy. Of all SMYD family proteins, SMYD3 adopt a closed conformation in a crystal structure. Several studies have suggested that the conformational changes between the open and closed forms may regulate the catalytic activity of SMYD3. In this work, we carried out extensive molecular dynamics simulations on a series of complexes with a total of 21 μs sampling to investigate the conformational changes of SMYD3 and unveil the molecular mechanisms. Based on the C-terminal domain movements, the simulated models could be depicted in three different conformational states: the closed, intermediate and open states. Only in the case that both the methyl donor binding pocket and the target lysine-binding channel had bound species did the simulations show SMYD3 maintaining its conformation in the closed state, indicative of a synergetic effect of the cofactors and target lysine on regulating the conformational change of SMYD3. In addition, we performed analyses in terms of structure and energy to shed light on how the two regions might regulate the C-terminal domain movement. This mechanistic study provided insights into the relationship between the conformational change and the methyltransferase activity of SMYD3. The more complete understanding of the conformational dynamics developed here together with further work may lay a foundation for the rational drug design of SMYD3 inhibitors.
Comparative Analysis of Mitogenomes among Five Species of Filchnerella (Orthoptera: Acridoidea: Pamphagidae) and Their Phylogenetic and Taxonomic Implications
Authors: Zheng Fang-Yuan , Shi Qiu-Yue , Ling Yao , Chen Jian-Yu , Zhang Bo-Fan , Li Xin-Jiang
Published: July 2021

Mitogenomes have been widely used for exploring phylogenetic analysis and taxonomic diagnosis. In this study, the complete mitogenomes of five species of Filchnerella were sequenced, annotated and analyzed. Then, combined with other seven mitogenomes of Filchnerella and four of Pamphagidae, the phylogenetic relationships were reconstructed by maximum likelihood (ML) and Bayesian (BI) methods based on PCGs+rRNAs. The sizes of the five complete mitogenomes are Filchnerella sunanensis 15,656 bp, Filchnerella amplivertica 15,657 bp, Filchnerella nigritibia 15,661 bp, Filchnerella pamphagoides 15,661 bp and Filchnerella dingxiensis 15,666 bp. The nucleotide composition of mitogenomes is biased toward A+T. All tRNAs could be folded into the typical clover-leaf structure, except that tRNA Ser (AGN) lacked a dihydrouridine (DHU) arm. The phylogenetic relationships of Filchnerella species based on mitogenome data revealed a general pattern of wing evolution from long wing to increasingly shortened wing.
Evaluation of the Impact of Eustenopus villosus on Centaurea solstitialis Seed Production in California
Authors: Pitcairn Michael , Woods Dale , Joley Donald , Turner Charles
Published: July 2021

The impact of the capitulum weevil Eustenopus villosus on Centaurea solstitialis seed production was examined at two field sites in central California. The study occurred in 1993–1995 during the early phases of the biological control program on C. solstitialis and before the current guild of capitulum insects had become widespread. Results showed that adult feeding on early flower buds resulted in 60–70% of buds failing to develop. Regrowth delayed capitulum production by 9 days and extended production by 4 weeks at season end. Between 69% and 92% of capitula were punctured from feeding or oviposition but the occurrence of larvae in capitula ranged from 27% to 49%. Seed production in C. solstitialis capitula increased linearly with size. The occurrence of larvae was proportionally higher in larger capitula (>8 mm) but the probability of attack for individual capitula did not vary with plant size. Total seed loss from larval feeding ranged from 34 to 47%. It is recommended that another survey be performed to determine if the level of infestation of E. villosus has increased since its initial introduction.
Meteorin Is a Novel Therapeutic Target for Wet Age-Related Macular Degeneration
Authors: Delaunay Kimberley , Sellam Alexandre , Dinet Virginie , Moulin Alexandre , Zhao Min , Gelizé Emmanuelle , Canonica Jérémie , Naud Marie-Christine , Crisanti-Lassiaz Patricia , Behar-Cohen Francine
Published: July 2021

The aim of this study was to evaluate the potential anti-angiogenic effect of MTRN (meteorin) in the laser-induced CNV rat model and explore its mechanisms of action. MTRN, thrompospondin-1, glial cell markers (GFAP, vimentin), and phalloidin were immuno-stained in non-human primate flat-mounted retinas and human retina cross sections. The effect of MTRN at different doses and time points was evaluated on laser-induced CNV at 14 days using in vivo fluorescein angiography and ex vivo quantification of CNV. A pan transcriptomic analysis of the retina and the RPE/choroid complex was used to explore MTRN effects mechanisms. In human retina, MTRN is enriched in the macula, expressed in and secreted by glial cells, and located in photoreceptor cells, including in nuclear bodies. Intravitreal MTRN administered preventively reduced CNV angiographic scores and CNV size in a dose-dependent manner. The highest dose, administered at day 7, also reduced CNV. MTRN, which is regulated by mineralocorticoid receptor modulators in the rat retina, regulates pathways associated with angiogenesis, oxidative stress, and neuroprotection. MTRN is a potential novel therapeutic candidate protein for wet AMD.
Delirium Severely Worsens Outcome in Patients with COVID-19—A Retrospective Cohort Study from Temporary Critical Care Hospitals
Authors: Kotfis Katarzyna , Witkiewicz Wojciech , Szylińska Aleksandra , Witkiewicz Karina , Nalewajska Magdalena , Feret Wiktoria , Wojczyński Łukasz , Duda Łukasz , Ely Eugene Wesley
Published: July 2021

Delirium is a sign of deterioration of homeostasis and worse prognosis. The aim of this study was to investigate the frequency, risk factors and prognosis of delirium in patients with COVID-19 in a temporary acute setting hospital. A retrospective cohort analysis of data collected between October 2020 and February 2021 from two temporary acute care hospitals was performed. All consecutive hospitalized patients ≥18 years old with COVID-19 were included. An assessment of consciousness was carried out at least two times a day, including neurological examination. Delirium was identified through retrospective chart review according to DSM-5 criteria if present at least once during hospitalization. Analysis included 201 patients, 39 diagnosed with delirium (19.4%). Delirious patients were older (p < 0.001), frailer (p < 0.001) and the majority were male (p = 0.002). Respiratory parameters were worse in this group with higher oxygen flow (p = 0.013), lower PaO2 (p = 0.043) and higher FiO2 (p = 0.006). The mortality rate was significantly higher in patients with delirium (46.15% vs 3.70%, p < 0.001) with OR 17.212 (p < 0.001) corrected for age and gender. Delirious patients experienced significantly more complications: cardiovascular (OR 7.72, p < 0.001), pulmonary (OR 8.79, p < 0.001) or septic (OR 3.99, p = 0.029). The odds of mortality in patients with COVID-19 presenting with delirium at any point of hospitalization were seventeen times higher.
The Long-Term Effect of Treatment Using the Transcranial Magnetic Stimulation rTMS in Patients after Incomplete Cervical or Thoracic Spinal Cord Injury
Authors: Wincek Agnieszka , Huber Juliusz , Leszczyńska Katarzyna , Fortuna Wojciech , Okurowski Stefan , Chmielak Krzysztof , Tabakow Paweł
Published: July 2021

Repetitive transcranial magnetic stimulation (rTMS) may support motor function recovery in patients with incomplete spinal cord injury (iSCI). Its effectiveness mainly depends on the applied algorithm. This clinical and neurophysiological study aimed to assess the effectiveness of high-frequency rTMS in iSCI patients at the C2–Th12 levels. rTMS sessions (lasting 3–5 per month, from 2 to 11 months, 5 months on average) were applied to 26 iSCI subjects. The motor cortex was bilaterally stimulated with a frequency at 20–25 Hz and a stimulus strength that was 70–80% of the resting motor threshold (15.4–45.5% maximal output) during one therapeutic session. Surface electromyography (sEMG) recordings at rest and during maximal contractions and motor evoked potential (MEP) recordings were performed from the abductor pollicis brevis (APB) and the tibialis anterior (TA) muscles. The same neurophysiological studies were also performed in patients treated with kinesiotherapy only (K group, n = 25) and compared with patients treated with both kinesiotherapy and rTMS (K + rTMS). A decrease in sEMG amplitudes recorded at rest from the APB muscles (p = 0.001) and an increase in sEMG amplitudes during the maximal contraction of the APB (p = 0.001) and TA (p = 0.009) muscles were found in the K + rTMS group. A comparison of data from MEP studies recorded from both APB and TA muscles showed significant changes in the mean amplitudes but not in latencies, suggesting a slight improvement in the transmission of spinal efferent pathways from the motor cortex to the lower spinal centers. The application of rTMS at 20–25 Hz reduced spasticity in the upper extremity muscles, improved the recruitment of motor units in the upper and lower extremity muscles, and slightly improved the transmission of efferent neural impulses within the spinal pathways in patients with C2–Th12 iSCI. Neurophysiological recordings produced significantly better parameters in the K + rTMS group of patients after therapy. These results may support the hypothesis about the importance of rTMS therapy and possible involvement of the residual efferent pathways including propriospinal neurons in the recovery of the motor control of iSCI patients.
Expression of Vascular Endothelial Growth Factor-C in the Trabecular Meshwork of Patients with Neovascular Glaucoma and Primary Open-Angle Glaucoma
Authors: Hase Keitaro , Kase Satoru , Kanda Atsuhiro , Shinmei Yasuhiro , Noda Kousuke , Ishida Susumu
Published: July 2021

To investigate the expression of vascular endothelial growth factor (VEGF)-C and vascular endothelial growth factor receptor (VEGFR)3 in the trabecular meshwork (TM) of patients with glaucoma and cultured TM cells. Methods: The expressions of VEGF-C in angle tissues collected by trabeculectomy from patients with glaucoma and non-glaucomatous choroidal malignant melanoma were analyzed by immunohistochemistry. Additionally, VEGF-C concentrations were determined in the aqueous humor of patients with glaucoma by ELISA. The expressions of VEGFR3, which is a receptor of VEGF-C in cultured TM cells, were analyzed by Western blot analysis and immunocytochemistry. Cultured TM cells were stimulated by oxidative stress, hypoxia, or high glucose conditions, and VEGF-C concentrations in supernatants and cell lysates were determined by ELISA. Results: VEGF-C immunoreactivity was positive in TM tissues of glaucoma patients, but not in those of non-glaucomatous controls. VEGF-C concentrations in the aqueous humor of patients with neovascular glaucoma and primary open-angle glaucoma were lower than those with non-glaucoma patients. VEGFR3 was expressed in cultured TM cells. VEGF-C concentrations in supernatants or cell lysates of TM cells cultured under oxidative stress and hypoxia were significantly elevated compared with those under steady conditions (p < 0.05). VEGF-C concentrations in supernatants and cell lysates of TM cells cultured in high glucose were significantly higher than those in low glucose (p < 0.01). Conclusions: VEGF-C was expressed in TM tissues of patients with glaucoma, which was secreted from cultured TM cells under various pathological conditions. These results suggest that VEGF-C may be involved in the pathology of glaucoma.
Sex Disparities in Long-Term Mortality after Paclitaxel Exposure in Patients with Peripheral Artery Disease: A Nationwide Claims-Based Cohort Study
Authors: Behrendt Christian-Alexander , Sedrakyan Art , Katsanos Konstantinos , Nordanstig Joakim , Kuchenbecker Jenny , Kreutzburg Thea , Secemsky Eric A. , Debus Eike Sebastian , Marschall Ursula , Peters Frederik
Published: July 2021

Background: Randomized controlled trials have reported excess mortality in patients treated with paclitaxel-coated devices versus uncoated devices, while observational studies have reported the opposite. This study aims to determine the underlying factors and cohort differences that may explain these opposite results, with specific focus on sex differences in treatment and outcomes. Methods: Multicenter health insurance claims data from a large insurance fund, BARMER, were studied. A homogeneous sample of patients with an index of endovascular revascularization for symptomatic peripheral arterial occlusive disease between 2013 and 2017 was included. Adjusted logistic regression and Cox regression models were used to determine the factors predicting allocation to paclitaxel-coated devices and sex-specific 5-year all-cause mortality, respectively. Results: In total, 13,204 patients (54% females, mean age 74 ± 11 years) were followed for a median of 3.5 years. Females were older (77 vs. 71 years), and had less frequent coronary artery disease (23% vs. 33%), dyslipidemia (44% vs. 50%), and diabetes (29% vs. 41%), as well as being less likely to have a history of smoking (10% vs. 15%) compared with males. Mortality differences were mostly attributable to the female subgroup who were revascularized above the knee (hazard ratio, HR 0.78, 95% CI: 0.64–0.95), while no statistically significant differences were observed in males. Conclusions: This study found that females treated above the knee benefited from paclitaxel-coated devices, while no differences were found in males. Ongoing and future registries and trials should take sex disparities into account.
Infill Design Reinforcement of 3D Printed Parts Using Refinement Technique Adapted to Continuous Extrusion
Authors: Madugula Sashi Kiran , Giraud-Moreau Laurence , Adragna Pierre-Antoine , Daniel Laurent
Published: July 2021

In this paper, we introduce an advanced numerical tool aimed to optimise the infill design of 3D printed parts by reducing printing time. In 3D printing, the term infill refers to the internal structure of a part. To create the infill design, slicing software is used, which generally creates the infill uniformly throughout the part. When such a part is subjected to external loading, all the infill regions will not experience the same amount of stress. Therefore, using uniform infill throughout the part is not the most optimised solution in terms of material usage. We do propose to evolve the infill design with respect to the mechanical stresses generated by the external loads. To achieve this, an advanced numerical tool has been developed, based on refinement techniques, to control the infill design. This tool is coupled with Finite Element Simulation (FE Simulation) software, which helps to identify the zones where the material is required as an infill to reinforce a part, whereas the refinement technique makes it possible to place the material as an infill in such a way that the airtime during the printing of the part is zero. Zero airtime printing is defined as the ability to deposit each layer of a part, without stopping the material extrusion during the displacement of the nozzle. Therefore, the proposed numerical tool guides us to generate the infill design of a part, in such a way that it will consume zero airtime while manufacturing. Simultaneously, it will increase the stiffness of the part. The proposed approach is here applied to a rectangular structure subjected to four-point bending, made up of PLA material (Poly-Lactic Acid).
Personalized Medicine in Oncology; a Special Issue of the Journal of Personalized Medicine
Authors: VanderWalde Ari
Published: July 2021

Nowhere is the explosion in comprehensive genomic testing more evident than in oncology [...]
Family Business in the Digital Age: The State of the Art and the Impact of Change in the Estimate of Economic Value
Authors: Ferraro Olga , Cristiano Elena
Published: July 2021

Throughout the review of the most relevant literature on family businesses and business valuation, this work pursues a twofold purpose: to explore the possible evolutionary scenarios of family businesses in the era of digitalisation, highlighting their role and purpose; and to determine the valuation approaches that may be applied to them, also in light of the different role that intangible assets deriving from their digitalisation may assume. Therefore, after a description of the most relevant changes related to the digital transformation of the FB, the focus will be set on their valuation, paying special attention to the choice of the most appropriate methodology for “grasping” the aforementioned changes. Family businesses, in fact, due to their distinctive traits and the various estimation opportunities, require a dynamic business valuation process that has to be projected into the future and suitable for estimating those intangible assets that strongly characterise these types of companies, inasmuch as they are related to the implicit components that are strongly connected to the ownership and are a result of knowledge, strategic adaptability, and product innovation, and their possible impact on the risks and their expected flows. Thus, throughout a systematic literature review, the study provides, on the one hand, a clearer representation of the state of the art of the FB valuation in the digital age; on the other hand, it highlights the characteristics and peculiarities of “novel” FBs whose valuation needs to be conducted with due care.
Agroforestry-Based Ecosystem Services: Reconciling Values of Humans and Nature in Sustainable Development
Authors: van Noordwijk Meine
Published: July 2021

Agroforestry as active area of multi-, inter-, and transdisciplinary research aims to bridge several artificial divides that have respectable historical roots but hinder progress toward sustainable development goals. These include: (1) The segregation of “forestry trees” and “agricultural crops”, ignoring the continuity in functional properties and functions; the farm-scale “Agroforestry-1” concept seeks to reconnect perennial and annual, woody and nonwoody plants across the forest–agriculture divide to markets for inputs and outputs. (2) The identification of agriculture with provisioning services and the assumed monopoly of forests on other ecosystem services (including hydrology, carbon storage, biodiversity conservation) in the landscape, challenged by the opportunity of “integrated” solutions at landscape scale as the “Agroforestry-2” concept explores. (3) The gaps among local knowledge of farmers/agroforesters as landscape managers, the contributions of social and ecological sciences, the path-dependency of forestry, environmental or agricultural institutions, and emerging policy responses to “issue attention cycles” in the public debate, as is the focus of the “Agroforestry-3” concept. Progress in understanding social–ecological–economic systems at the practitioners–science–policy interface requires that both instrumental and relational values of nature are appreciated, as they complement critical steps in progressing issue cycles at the three scales. A set of hypotheses can guide further research.
Monitoring and Modeling the Patterns and Trends of Urban Growth Using Urban Sprawl Matrix and CA-Markov Model: A Case Study of Karachi, Pakistan
Authors: Baqa Muhammad Fahad , Chen Fang , Lu Linlin , Qureshi Salman , Tariq Aqil , Wang Siyuan , Jing Linhai , Hamza Salma , Li Qingting
Published: July 2021

Understanding the spatial growth of cities is crucial for proactive planning and sustainable urbanization. The largest and most densely inhabited megapolis of Pakistan, Karachi, has experienced massive spatial growth not only in the core areas of the city, but also in the city’s suburbs and outskirts over the past decades. In this study, the land use/land cover (LULC) in Karachi was classified using Landsat data and the random forest algorithm from the Google Earth Engine cloud platform for the years 1990, 2000, 2010, and 2020. Land use/land cover classification maps as well as an urban sprawl matrix technique were used to analyze the geographical patterns and trends of urban sprawl. Six urban classes, namely, the primary urban core, secondary urban core, sub-urban fringe, scatter settlement, urban open space, and non-urban area, were determined for the exploration of urban landscape changes. Future scenarios of LULC for 2030 were predicted using a CA–Markov model. The study found that the built-up area had expanded in a considerably unpredictable manner, primarily at the expense of agricultural land. The increase in mangroves and grassland and shrub land proved the effectiveness of afforestation programs in improving vegetation coverage in the study area. The investigation of urban landscape alteration revealed that the primary urban core expanded from the core districts, namely, the Central, South, and East districts, and a new urban secondary core emerged in Malir in 2020. The CA–Markov model showed that the total urban built-up area could potentially increase from 584.78 km2 in 2020 to 652.59 km2 in 2030. The integrated method combining remote sensing, GIS, and an urban sprawl matrix has proven invaluable for the investigation of urban sprawl in a rapidly growing city.
2-(2-(Fluorosulfonyloxy)phenyl)benzoxazole
Authors: Danilenko Nadezhda , Shmalyuk Vladimir , Khlebnikov Andrei
Published: July 2021

The fluorosulfate derivatives of benzoxazole attract attention since benzoxazole-based compounds have a wide range of biological activities, and the ability of the –SO2F group to react with various functional groups makes it possible to synthesize various new derivatives. The new 2-(2-(fluorosulfonyloxy)phenyl)benzoxazole (2) has been synthesized by the SuFEx click reaction in a two-chamber reactor. Compound 2 is the first example of a benzoxazole derivative with a fluorosulfate-containing substituent at position two of the benzoxazole heterocycle. The anti-cancer potency of 2 was evaluated in silico using molecular docking. The docking results suggest that title compound 2 is of great interest for further studies as a possible anaplastic lymphoma kinase inhibitor.
Unexpected Formation of 4-aryl-1-(Propane-2-ylidenehydrazono)-2,3-diazaspiro[5.5]undec-3-ene by the Reaction of Pyridazinethiones Derivatives with Hydrazine
Authors: Sepsey Für Csilla , Keglevich György , Bölcskei Hedvig
Published: July 2021

After making a new series of spiro[cycloalkane]pyridazinones with high Fsp3 character available, the new target was to synthesize derivatives comprising nitrogen-containing heterocycles, such as triazolo or tetrazolo rings. The corresponding thioxo derivatives (1a,b) seemed to be good starting materials for the synthesis of tetrazolo derivatives. The reaction of the pyridazinethiones (1a,b) with hydrazine surprisingly resulted in Schiff bases (3a,b) deriving from the reaction of hydrazones (2a,b) with acetone.
N-{2-[(3-Oxo-1,3-dihydro-2-benzofuran-1-yl)acetyl]phenyl}acetamide
Authors: Rodríguez Ricaurte , León Omar , Quiroga Felipe , Cifuentes Jonnathan
Published: July 2021

With the aim of obtaining different derivatives belonging to the isoindolo[2,1-a]quinoline family, we have synthesized a novel N-{2-[(3-oxo-1,3-dihydro-2-benzofuran-1-yl)acetyl]phenyl}acetamide derivative by a Claisen–Smichdt-type condensation reaction in 75% yield.
Relationship between the Surface Roughness of Material and Bone Cement: An Increased “Polished” Stem May Result in the Excessive Taper-Slip
Authors: Hirata Masayuki , Oe Kenichi , Kaneuji Ayumi , Uozu Ryusuke , Shintani Kazuhiro , Saito Takanori
Published: July 2021

Although some reports suggest that taper-slip cemented stems may be associated with a higher periprosthetic femoral fractures rate than composite-beam cemented stems, few studies have focused on the biomaterial effect of the polished material on the stem–cement interface. The purpose of this study was to investigate the relationship between surface roughness of materials and bone cement. Four types of metal discs—cobalt-chromium-molybdenum alloy (CoCr), stainless steel alloy 316 (SUS), and two titanium alloys (Ti-6Al-4V and Ti-15Mo-5Zr-3Al)—were prepared. Five discs of each material were produced with varying degrees of surface roughness. In order to evaluate surface wettability, the contact angle was measured using the sessile drop method. A pin was made using two bone cements and the frictional coefficient was assessed with a pin-on-disc test. The contact angle of each metal increased with decreasing surface roughness and the surface wettability of metal decreased with higher degrees of polishing. With a surface roughness of Ra = 0.06 μm and moderate viscosity bone cement, the frictional coefficient was significantly lower in CoCr than in SUS (p = 0.0073). In CoCr, the low adhesion effect with low frictional coefficient may result in excessive taper-slip, especially with the use of moderate viscosity bone cement.
Macromonomers as a Novel Way to Investigate and Tailor Silicon-Oxycarbide-Based Materials Obtained from Polymeric Preceramic Precursors
Authors: Owińska Maria , Matoga Paulina , Jeleń Piotr , Długoń Elżbieta , Handke Bartosz , Niemiec Wiktor
Published: July 2021

It has been shown that bifunctional monomers (D units), which are used to increase the carbon content in silicon oxycarbide precursors, can form volatile oligomers, thus affecting the amount of carbon available during the transition into the final material in the annealing process. Additionally, an uneven distribution of carbon-rich mers may lead to the formation of a free-carbon phase, instead of the incorporation of carbon atoms into the silicon matrix. In this study, a novel two-step approach was utilized. Firstly, a macromonomer containing a number of structural units with precise structure was synthesized, which was later polycondensed into a ceramic precursor. Chlorodimethylsilane modified 2,4,6,8-tetramethylcyclotetrasiloxane was used as a silicon oxycarbide precursor monomer containing both T and D structural units (i.e., silicon atoms bonded to three and two oxygen atoms, respectively), with well-defined interconnections between structural units. Such a macromonomer prevents the formation of small siloxane rings, and has a very limited number of possible combinations of structural units neighboring each silicon atom. This, after investigation using IR, XRD, TG and elemental analysis, gave insight into the effect of “anchoring” silicon atoms bonded to two methyl groups, as well as the impact of their distribution in comparison to the materials obtained using simple monomers containing a single silicon atom (structural unit).
Improvement of Bond Strength and Durability of Recycled Aggregate Concrete Incorporating High Volume Blast Furnace Slag
Authors: Lin Shu-Ken , Wu Chung-Hao
Published: July 2021

This paper aims to experimentally investigate the effects of high volume cement replacement of blast furnace slag (BFS) on the bond, strength and durability of recycled aggregate concrete (RAC). Concrete mixtures were prepared containing 0%, 15%, 30%, 45%, 60% and 75% BFS with each of recycled aggregate and natural aggregate. Measurements of the compressive and bond strength, the resistance to chloride-ion penetration and the water permeability of concrete are reported. In addition, a microhardness test was also performed to evaluate the quality of interfacial transition zone (ITZ) in concrete. Test results of the bond strength and the compressive strength of RAC mixtures, in spite of the cement replacement amount with BFS, show that the concretes result in reduced strength when compared to natural aggregate concrete (NAC) mixtures, while the strength gains for the BFS-based concrete are higher than that of the reference mixtures without BFS at long-term ages. Incorporating BFS in concrete can inherently improve the durability properties by increasing higher resistance to chloride-ion penetration and lower water permeability. This improvement in the mechanical and durability properties of the BFS-based RAC mixture may be due to the additional pozzolanic reaction of BFS, which enhances the properties of ITZ in concrete, resulting in an improvement of the strength of concrete.