bluuebunny/crossref_metadata_2025_split huggingface dataset:
Biomechanical effects of lumbar fusion surgery on adjacent segments using musculoskeletal models of the intact, degenerated and fused spine
Authors: Ebrahimkhani Mahdi , Arjmand Navid , Shirazi-Adl Aboulfazl 
Published: September 2021

AbstractAdjacent segment disorders are prevalent in patients following a spinal fusion surgery. Postoperative alterations in the adjacent segment biomechanics play a role in the etiology of these conditions. While experimental approaches fail to directly quantify spinal loads, previous modeling studies have numerous shortcomings when simulating the complex structures of the spine and the pre/postoperative mechanobiology of the patient. The biomechanical effects of the L4–L5 fusion surgery on muscle forces and adjacent segment kinetics (compression, shear, and moment) were investigated using a validated musculoskeletal model. The model was driven by in vivo kinematics for both preoperative (intact or severely degenerated L4–L5) and postoperative conditions while accounting for muscle atrophies. Results indicated marked changes in the kinetics of adjacent L3–L4 and L5–S1 segments (e.g., by up to 115% and 73% in shear loads and passive moments, respectively) that depended on the preoperative L4–L5 disc condition, postoperative lumbopelvic kinematics and, to a lesser extent, postoperative changes in the L4–L5 segmental lordosis and muscle injuries. Upper adjacent segment was more affected post-fusion than the lower one. While these findings identify risk factors for adjacent segment disorders, they indicate that surgical and postoperative rehabilitation interventions should focus on the preservation/restoration of patient’s normal segmental kinematics.
Antibacterial and molecular docking studies of newly synthesized nucleosides and Schiff bases derived from sulfadimidines
Authors: Amer Hamada H. , Eldrehmy Essam Hassan , Abdel-Hafez Salama Mostafa , Alghamdi Youssef Saeed , Hassan Magdy Yassin , Alotaibi Saad H. 
Published: September 2021

AbstractA new series of nucleosides, moieties, and Schiff bases were synthesized from sulfadimidine. Infrared (IR), 1HNMR, 13C NMR, and mass spectrometry techniques and elemental analysis were employed to elucidate the synthesized compounds. The prepared analogues were purified by different chromatographic techniques (preparative TLC and column chromatography). Molecular docking studies of synthesized compounds 3a, 4b, 6a, and 6e demonstrated the binding mode involved in the active site of DNA gyrase. Finally, all synthesized compounds were tested against selected bacterial strains. The most effective synthesized compounds against S. aureus were 3a, 4d, 4b, 3b, 3c, 4c, and 6f, which exhibited inhibition zones of inhibition of 24.33 ± 1.528, 24.67 ± 0.577, 23.67 ± 0.577, 22.33 ± 1.528, 18.67 ± 1.528 and 19.33 ± 0.577, respectively. Notably, the smallest zones were observed for 4a, 6d, 6e and 6g (6.33 ± 1.528, 11.33 ± 1.528, 11.67 ± 1.528 and 14.66 ± 1.155, respectively). Finally, 6b and 6c gave negative zone values. K. pneumoniae was treated with the same compounds and the following results were obtained. The most effective compounds were 4d, 4c, 4b and 3c, which showed inhibition zones of 29.67 ± 1.528, 24.67 ± 0.577, 23.67 ± 1.155 and 19.33 ± 1.528, respectively, followed by 4a and 3d (15.33 ± 1.528 for both), while moderate results (13.67 ± 1.155 and 11.33 ± 1.528) were obtained for 6f and 6g, respectively. Finally, 6a, 6b, 6c, 3a, and 3b did not show any inhibition. The most effective compounds observed for the treatment of E. coli were 4d, 4b, 4c, 3d, 6e and 6f (inhibition zones of 26.33 ± 0.577, 21.67 ± 1.528, 21.67 ± 1.528, 19.67 ± 1.528, 17.67 ± 1.155 and 16.67 ± 1.155, respectively). Compounds 3b, 3c, 6a, 6c, and 6g gave moderate results (13.67 ± 1.528, 12.67 ± 1.528, 11.33 ± 0.577, 15.33 ± 1.528 and 12.67 ± 1.528, respectively), while 6b showed no effect. The MIC values against S. aureus ranged from 50 to 3.125 mg, while those against E. coli and K. pneumoniae ranged from 50 to 1562 mg. In vitro, the antibacterial effects were promising. Further research is required to study the in vivo antibacterial effects of these compounds and determine therapeutic doses.
Eng2, a new player involved in feedback loop regulation of Cdc42 activity in fission yeast
Authors: García Patricia , Coll Pedro M. , del Rey Francisco , Geli M. Isabel , Pérez Pilar , Vázquez de Aldana Carlos R. , Encinar del Dedo Javier 
Published: September 2021

AbstractCell polarity and morphogenesis are regulated by the small GTPase Cdc42. Even though major advances have been done in the field during the last years, the molecular details leading to its activation in particular cellular contexts are not completely understood. In fission yeast, the β(1,3)-glucanase Eng2 is a “moonlighting protein” with a dual function, acting as a hydrolase during spore dehiscence, and as component of the endocytic machinery in vegetative cells. Here, we report that Eng2 plays a role in Cdc42 activation during polarized growth through its interaction with the scaffold protein Scd2, which brings Cdc42 together with its guanine nucleotide exchange factor (GEF) Scd1. eng2Δ mutant cells have defects in activation of the bipolar growth (NETO), remaining monopolar during all the cell cycle. In the absence of Eng2 the accumulation of Scd1 and Scd2 at the poles is reduced, the levels of Cdc42 activation decrease, and the Cdc42 oscillatory behavior, associated with bipolar growth in wild type cells, is altered. Furthermore, overexpression of Eng2 partially rescues the growth and polarity defects of a cdc42-L160S mutant. Altogether, our work unveils a new factor regulating the activity of Cdc42, which could potentially link the polarity and endocytic machineries.
Shaping light in 3d space by counter-propagation
Authors: Droop Ramon , Asché Eric , Otte Eileen , Denz Cornelia 
Published: September 2021

AbstractWe extend the established transverse customization of light, in particular, amplitude, phase, and polarization modulation of the light field, and its analysis by the third, longitudinal spatial dimension, enabling the visualization of longitudinal structures in sub-wavelength (nm) range. To achieve this high-precision and three-dimensional beam shaping and detection, we propose an approach based on precise variation of indices in the superposition of higher-order Laguerre-Gaussian beams and cylindrical vector beams in a counter-propagation scheme. The superposition is analyzed experimentally by digital, holographic counter-propagation leading to stable, reversible and precise scanning of the light volume. Our findings show tailored amplitude, phase and polarization structures, adaptable in 3D space by mode indices, including sub-wavelength structural changes upon propagation, which will be of interest for advanced material machining and optical trapping.
Sequencing and characterization of an L-asparaginase gene from a new species of Penicillium section Citrina isolated from Cerrado
Authors: Andrade Kellen C. R. , Fernandes Rildo A. , Pinho Danilo Batista , de Freitas Marcela M. , Filho Edivaldo Ximenes Ferreira , Pessoa Adalberto , Silva João Inácio , Magalhães Perola O. 
Published: September 2021

AbstractThe enzyme L-asparaginase (L-ASNase) is used in the treatment of Acute Lymphoblastic Leukemia. The preparations of this enzyme for clinical use are derived from bacterial sources and its use is associated with serious adverse reactions. In this context, it is important to find new sources of L-ASNase. In this work, the Placket-Burman Experimental Design (PBD) was used to determine the influence of the variables on the L-ASNase production then it was followed by a 28–4 Factorial Fractional Design (FFD). The results obtained from PBD have shown a range of L-ASNase activity, from 0.47 to 1.77 U/gcell and the results obtained from FFD have showed a range of L-ASNase activity, from 1.10 to 2.36 U/gcell. L-proline and ammonium sulfate were identified as of significant positive variables on this production enzyme by Penicillium cerradense sp. nov. The precise identification of this new species was confirmed by morphological characteristics and sequence comparisons of the nuclear 18S-5.8S-28S partial nrDNA including the ITS1 and ITS2 regions, RNA polymerase II, β-tubulin and calmodulin genomic regions. The genetic sequence coding for the L-ASNase was obtained after carrying out a full genome sequencing. The L-ASNase expressed by P. cerradense sp. nov may have promising antineoplastic properties.
Tracking slab surface temperatures with electrical conductivity of glaucophane
Authors: Manthilake Geeth , Peng Ye , Koga Kenneth T. , Mookherjee Mainak 
Published: September 2021

AbstractSlab surface temperature is one of the key parameters that incur first-order changes in subduction dynamics. However, the current thermal models are based on empirical thermal parameters and do not accurately capture the complex pressure–temperature paths of the subducting slab, prompting significant uncertainties on slab temperature estimations. In this study, we investigate whether the dehydration-melting of glaucophane can be used to benchmark the temperature in the slab. We observe that dehydration and melting of glaucophane occur at relatively low temperatures compared to the principal hydrous phases in the slab and produce highly conductive Na-rich melt. The electrical properties of glaucophane and its dehydration products are notably different from the hydrous minerals and silicate melts. Hence, we conclude that the thermodynamic instability of glaucophane in the slab provides a unique petrological criterion for tracking temperature in the present-day subduction systems through magnetotelluric profiles.
Pharmacological characterization of mutant huntingtin aggregate-directed PET imaging tracer candidates
Authors: Herrmann Frank , Hessmann Manuela , Schaertl Sabine , Berg-Rosseburg Karola , Brown Christopher J , Bursow Galina , Chiki Anass , Ebneth Andreas , Gehrmann Miriam , Hoeschen Nicole , Hotze Madlen , Jahn Stefanie , Johnson Peter D , Khetarpal Vinod , Kiselyov Alex , Kottig Karsten , Ladewig Stefanie , Lashuel Hilal , Letschert Sven , Mills Matthew R , Petersen Kathrin , Prime Michael E , Scheich Christoph , Schmiedel Gerhard , Wityak John , Liu Longbin , Dominguez Celia , Muñoz-Sanjuán Ignacio , Bard Jonathan A 
Published: September 2021

AbstractHuntington’s disease (HD) is caused by a CAG trinucleotide repeat expansion in the first exon of the huntingtin (HTT) gene coding for the huntingtin (HTT) protein. The misfolding and consequential aggregation of CAG-expanded mutant HTT (mHTT) underpin HD pathology. Our interest in the life cycle of HTT led us to consider the development of high-affinity small-molecule binders of HTT oligomerized/amyloid-containing species that could serve as either cellular and in vivo imaging tools or potential therapeutic agents. We recently reported the development of PET tracers CHDI-180 and CHDI-626 as suitable for imaging mHTT aggregates, and here we present an in-depth pharmacological investigation of their binding characteristics. We have implemented an array of in vitro and ex vivo radiometric binding assays using recombinant HTT, brain homogenate-derived HTT aggregates, and brain sections from mouse HD models and humans post-mortem to investigate binding affinities and selectivity against other pathological proteins from indications such as Alzheimer’s disease and spinocerebellar ataxia 1. Radioligand binding assays and autoradiography studies using brain homogenates and tissue sections from HD mouse models showed that CHDI-180 and CHDI-626 specifically bind mHTT aggregates that accumulate with age and disease progression. Finally, we characterized CHDI-180 and CHDI-626 regarding their off-target selectivity and binding affinity to beta amyloid plaques in brain sections and homogenates from Alzheimer’s disease patients.
Role of CXCL10 in the progression of in situ to invasive carcinoma of the breast
Authors: Kim Milim , Choi Hye Yeon , Woo Ji Won , Chung Yul Ri , Park So Yeon 
Published: September 2021

AbstractTumor immune microenvironment plays a crucial role in tumor progression. We performed immune profiling to compare immune-related gene expression between ductal carcinoma in situ (DCIS) and invasive carcinoma of the breast using nCounter PanCancer immune Profiling Panel and found that CXCL10 was the most significant gene that had the highest difference in expression between them. Effect of CXCL10 on breast cancer cell proliferation and invasion was examined in vitro, and expression of CXCL10 and its relationship with immune cell infiltration was assessed in breast cancer samples. CXCL10 induced cell proliferation, migration and epithelial-mesenchymal transition in MCF-7 and MDA-MB-231 breast cancer cell lines. We confirmed that CXCL10 mRNA expression was significantly higher in invasive carcinoma than in DCIS, especially in hormone receptor (HR)-negative tumors using a validation set. CXCL10 mRNA expression showed a positive correlation with tumor infiltrating lymphocyte (TIL) density in both DCIS and invasive carcinoma; CXCL10-positive tumors generally showed higher infiltration of CD8+ and FOXP3+TILs as well as PD-L1+ immune cells compared to CXCL10-negative tumors, albeit with different patterns according to HR status. In conclusion, our study showed that CXCL10 promotes tumor cell proliferation, invasion, and immune cell infiltration, implying its contribution in the progression of DCIS to invasive carcinoma of the breast.
Depletion of PD-1 or PD-L1 did not affect the mortality of mice infected with Mycobacterium avium
Authors: Nakajima Masayuki , Matsuyama Masashi , Kawaguchi Mio , Matsumura Sosuke , Kiwamoto Takumi , Matsuno Yosuke , Morishima Yuko , Yoshida Kazufumi , Sherpa Mingma Thsering , Yazaki Kai , Tanaka Ryota , Okiyama Naoko , Muratani Masafumi , Ishii Yukio , Hizawa Nobuyuki 
Published: September 2021

AbstractThe programmed cell death-1 (PD-1) and programmed cell death-ligand 1 (PD-L1) pathway could affect antimicrobial immune responses by suppressing T cell activity. Several recent studies demonstrated that blocking of the PD-1/PD-L1 pathway exacerbated Mycobacterium tuberculosis infection. However, the effect of blocking this pathway in pulmonary Mycobacterium avium–intracellulare complex (MAC) infection is not fully understood. Wild-type, PD-1-deficient mice, and PD-L1-deficient mice were intranasally infected with Mycobacterium avium bacteria. Depletion of PD-1 or PD-L1 did not affect mortality and bacterial burden in MAC-infected mice. However, marked infiltration of CD8-positive T lymphocytes was observed in the lungs of PD-1 and PD-L1-deficient mice compared to wild-type mice. Comprehensive transcriptome analysis showed that levels of gene expressions related to Th1 immunity did not differ according to the genotypes. However, genes related to the activity of CD8-positive T cells and related chemokine activity were upregulated in the infected lungs of PD-1 and PD-L1-deficient mice. Thus, the lack of change in susceptibility to MAC infection in PD-1 and PD-L1-deficient mice might be explained by the absence of obvious changes in the Th1 immune response. Furthermore, activated CD8-positive cells in response to MAC infection in these mice seemed to not be relevant in the control of MAC infection.
The impact of Hurricane Katrina, a major natural disaster, on assisted reproductive outcomes through an analysis of 451,848 ART cycles
Authors: Meir Olcha , Satu Kuokkanen , Xie Xianhong , Abdissa Negassa , Lubna Pal , Sangita Jindal 
Published: September 2021

AbstractTo evaluate whether pregnancies conceived via assisted reproductive technology and exposed to Hurricane Katrina (HK), one of the most destructive natural disasters in United States history, were more prone to adverse perinatal outcomes, miscarriages, or sex disparities compared with pregnancies established but not directly exposed to the natural disaster. Retrospective cohort study. Women 18 years and older undergoing fresh ART cycles that resulted in singleton pregnancies and entered in the SART CORS database from 2004 to 2008. Incidence of full-term and preterm delivery, miscarriage rate, infant weight at birth, and infant sex ratio. Total follicle stimulating hormone (FSH) stimulation dosage and number of oocytes retrieved. Between January 2004 and December 2008, a total of 451,848 fresh autologous IVF cycles were recorded in SART CORS, leading to 190,624 pregnancies and 129,499 live births. After controlling for potential confounders, our results demonstrate no association between HK exposure and overall preterm deliveries (< 37 weeks) in women with singleton pregnancies conceived after ART. Other perinatal outcomes such as rate of spontaneous abortion or infant weight at birth in the exposed and unexposed groups were also not associated with HK. A comparison of pre and post disaster sex ratios revealed fewer males were born after HK (51.0% vs. 49.4%), showing a trend of decreased male infant births that was least in part associated with HK (CI 0.81–1.01; p = 0.07). Exposure to HK did not appear to affect perinatal outcomes such as the rate of preterm delivery or the rate of spontaneous abortion. Extreme stress may be a factor that contributes to a reduced male to female secondary sex ratio.
Optimal single sampling time-point for monitoring of praziquantel exposure in children
Authors: Mnkugwe Rajabu Hussein , Ngaimisi Kitabi Eliford , Kinung’hi Safari , Kamuhabwa Appolinary A. R. , Minzi Omary Mashiku , Aklillu Eleni 
Published: September 2021

AbstractPraziquantel pharmacokinetics studies in schistosomiasis infected children are scarce partly due to the challenges/complexity of intensive blood sampling in the target population. This study was aimed to investigate the optimal single sampling time-point for monitoring praziquantel exposure. This was intensive pharmacokinetic study conducted among 32 Schistosoma mansoni infected children treated with an oral standard single-dose 40 mg/kg praziquantel. Plasma samples were collected at 0, 1, 2, 4, 6 and 8 h post-praziquantel administration. Quantification of praziquantel and its enantiomers (R- and S-praziquantel) concentrations was done by Liquid chromatography-tandem mass spectrometer (LC–MS/MS). The correlation between area under the plasma concentration–time curve from 0 to 8 h (AUC8) and plasma concentrations at each specific sampling time-point was determined by Pearson’s correlation coefficient (r2). The median age (range) of the study population was 12.5 years (10–17). The study participants were 17 males and 15 females. Both total praziquantel and its enantiomers (R- and S-praziquantel) displayed a wide inter-individual pharmacokinetic variability. Regression analysis indicated that, plasma concentrations collected at 4 h post-dose had a significantly highest correlation with the AUC8 for both total praziquantel (r2 = 0.81, p < 0.001) and S-praziquantel (r2 = 0.84, p < 0.001) than any other sampling time-point; while for R-praziquantel, plasma concentrations collected at 6 h sampling time-point had a significantly highest correlation with the AUC8 (r2 = 0.79, p < 0.001) than any other sampling time-point. Four hours sampling time-point post-praziquantel administration is ideal optimal single sampling time-point for therapeutic monitoring of total praziquantel exposure while 6 h sampling time-point is suitable for monitoring of a pharmacologically active R-praziquantel enantiomer.
Effect of metformin treatment and its time of administration on joint capsular fibrosis induced by mouse knee immobilization
Authors: Tokuda Kotaro , Yamanaka Yoshiaki , Mano Yosuke , Tsukamoto Manabu , Tajima Takafumi , Suzuki Hitoshi , Kawasaki Makoto , Uchida Soshi , Nakamura Eiichiro , Wang Ke-Yong , Sakai Akinori 
Published: September 2021

AbstractJoint contracture leads to major patient discomfort. Metformin, one of the most extensively used oral drugs against type 2 diabetes has recently been found to suppress tissue fibrosis as well. However, its role in suppressing tissue fibrosis in joint contractures remains unknown. In this study, we examined the role of metformin treatment in suppressing joint capsular fibrosis and the most effective time of its administration. Joint capsular fibrosis was induced by immobilizing the knee joints of mice using splints and tapes. Metformin was administered intraperitoneally every alternate day after immobilization. Histological and immunohistochemical changes and expression of fibrosis-related genes were evaluated. Metformin treatment significantly suppressed fibrosis in joint capsules based on histological and immunohistochemical evaluation. Joint capsular tissue from metformin-treated mice also showed decreased expression of fibrosis-related genes. Early, but not late, metformin administration showed the same effect on fibrosis suppression in joint capsule as the whole treatment period. The expression of fibrosis-related genes was most suppressed in mice administered with metformin early. These studies demonstrated that metformin treatment can suppress joint capsular fibrosis and the most effective time to administer it is early after joint immobilization; a delay of more than 2 weeks of administration is less effective.
Automated machine learning for endemic active tuberculosis prediction from multiplex serological data
Authors: Rashidi Hooman H. , Dang Luke T. , Albahra Samer , Ravindran Resmi , Khan Imran H. 
Published: September 2021

AbstractSerological diagnosis of active tuberculosis (TB) is enhanced by detection of multiple antibodies due to variable immune responses among patients. Clinical interpretation of these complex datasets requires development of suitable algorithms, a time consuming and tedious undertaking addressed by the automated machine learning platform MILO (Machine Intelligence Learning Optimizer). MILO seamlessly integrates data processing, feature selection, model training, and model validation to simultaneously generate and evaluate thousands of models. These models were then further tested for generalizability on out-of-sample secondary and tertiary datasets. Out of 31 antigens evaluated, a 23-antigen model was the most robust on both the secondary dataset (TB vs healthy) and the tertiary dataset (TB vs COPD) with sensitivity of 90.5% and respective specificities of 100.0% and 74.6%. MILO represents a user-friendly, end-to-end solution for automated generation and deployment of optimized models, ideal for applications where rapid clinical implementation is critical such as emerging infectious diseases.