bluuebunny/crossref_metadata_2025_split huggingface dataset:
Disease-related Huntingtin seeding activities in cerebrospinal fluids of Huntington’s disease patients
Authors: Lee C. Y. Daniel , Wang Nan , Shen Koning , Stricos Matthew , Langfelder Peter , Cheon Kristina H. , Cortés Etty P. , Vinters Harry V. , Vonsattel Jean Paul , Wexler Nancy S. , Damoiseaux Robert , Frydman Judith , Yang X. William 
Published: November 2020

AbstractIn Huntington’s disease (HD), the mutant Huntingtin (mHTT) is postulated to mediate template-based aggregation that can propagate across cells. It has been difficult to quantitatively detect such pathological seeding activities in patient biosamples, e.g. cerebrospinal fluids (CSF), and study their correlation with the disease manifestation. Here we developed a cell line expressing a domain-engineered mHTT-exon 1 reporter, which showed remarkably high sensitivity and specificity in detecting mHTT seeding species in HD patient biosamples. We showed that the seeding-competent mHTT species in HD CSF are significantly elevated upon disease onset and with the progression of neuropathological grades. Mechanistically, we showed that mHTT seeding activities in patient CSF could be ameliorated by the overexpression of chaperone DNAJB6 and by antibodies against the polyproline domain of mHTT. Together, our study developed a selective and scalable cell-based tool to investigate mHTT seeding activities in HD CSF, and demonstrated that the CSF mHTT seeding species are significantly associated with certain disease states. This seeding activity can be ameliorated by targeting specific domain or proteostatic pathway of mHTT, providing novel insights into such pathological activities.
VZHE-039, a novel antisickling agent that prevents erythrocyte sickling under both hypoxic and anoxic conditions
Authors: Abdulmalik Osheiza , Pagare Piyusha P. , Huang Boshi , Xu Guoyan G. , Ghatge Mohini S. , Xu Xiaomeng , Chen Qiukan , Anabaraonye Nancy , Musayev Faik N. , Omar Abdelsattar M. , Venitz Jürgen , Zhang Yan , Safo Martin K. 
Published: November 2020

AbstractSickle cell disease (SCD) results from a hemoglobin (Hb) mutation βGlu6 → βVal6 that changes normal Hb (HbA) into sickle Hb (HbS). Under hypoxia, HbS polymerizes into rigid fibers, causing red blood cells (RBCs) to sickle; leading to numerous adverse pathological effects. The RBC sickling is made worse by the low oxygen (O2) affinity of HbS, due to elevated intra-RBC concentrations of the natural Hb effector, 2,3-diphosphoglycerate. This has prompted the development of Hb modifiers, such as aromatic aldehydes, with the intent of increasing Hb affinity for O2 with subsequent prevention of RBC sickling. One such molecule, Voxelotor was recently approved by U.S. FDA to treat SCD. Here we report results of a novel aromatic aldehyde, VZHE-039, that mimics both the O2-dependent and O2-independent antisickling properties of fetal hemoglobin. The latter mechanism of action—as elucidated through crystallographic and biological studies—is likely due to disruption of key intermolecular contacts necessary for stable HbS polymer formation. This dual antisickling mechanism, in addition to VZHE-039 metabolic stability, has translated into significantly enhanced and sustained pharmacologic activities. Finally, VZHE-039 showed no significant inhibition of several CYPs, demonstrated efficient RBC partitioning and high membrane permeability, and is not an efflux transporter (P-gp) substrate.
Exploratory study of how Cognitive Multisensory Rehabilitation restores parietal operculum connectivity and improves upper limb movements in chronic stroke
Authors: Van de Winckel A. , De Patre D. , Rigoni M. , Fiecas M. , Hendrickson T. J. , Larson M. , Jagadeesan B. D. , Mueller B. A. , Elvendahl W. , Streib C. , Ikramuddin F. , Lim K. O. 
Published: November 2020

AbstractCognitive Multisensory Rehabilitation (CMR) is a promising therapy for upper limb recovery in stroke, but the brain mechanisms are unknown. We previously demonstrated that the parietal operculum (parts OP1/OP4) is activated with CMR exercises. In this exploratory study, we assessed the baseline difference between OP1/OP4 functional connectivity (FC) at rest in stroke versus healthy adults to then explore whether CMR affects OP1/OP4 connectivity and sensorimotor recovery after stroke. We recruited 8 adults with chronic stroke and left hemiplegia/paresis and 22 healthy adults. Resting-state FC with the OP1/OP4 region-of-interest in the affected hemisphere was analysed before and after 6 weeks of CMR. We evaluated sensorimotor function and activities of daily life pre- and post-CMR, and at 1-year post-CMR. At baseline, we found decreased FC between the right OP1/OP4 and 34 areas distributed across all lobes in stroke versus healthy adults. After CMR, only four areas had decreased FC compared to healthy adults. Compared to baseline (pre-CMR), participants improved on motor function (MESUPES arm p = 0.02; MESUPES hand p = 0.03; MESUPES total score p = 0.006); on stereognosis (p = 0.03); and on the Frenchay Activities Index (p = 0.03) at post-CMR and at 1-year follow-up. These results suggest enhanced sensorimotor recovery post-stroke after CMR. Our results justify larger-scale studies.
Enhancing second-harmonic generation with electron spill-out at metallic surfaces
Authors: Khalid Muhammad , Ciracì Cristian 
Published: November 2020

AbstractSecond-order nonlinear optical processes do not manifest in the bulk of centrosymmetric materials, but may occur in the angstroms-thick layer at surfaces. At such length scales, quantum mechanical effects come into play which could be crucial for an accurate description of plasmonic systems. In this article, we develop a theoretical model based on the quantum hydrodynamic description to study free-electron nonlinear dynamics in plasmonic systems. Our model predicts strong resonances induced by the spill-out of electron density at the metal surface. We show that these resonances can boost second-harmonic generation efficiency up to four orders of magnitude and can be arbitrarily tuned by controlling the electron spill-out at the metal surface with the aid of thin dielectric layers. These results offer a possibility to artificially increase nonlinear susceptibilities by engineering optical properties at the quantum level.
Recombinant collagen polypeptide as a versatile bone graft biomaterial
Authors: Fushimi Hideo , Hiratsuka Takahiro , Okamura Ai , Ono Yoshitaka , Ogura Izumi , Nishimura Ichiro 
Published: November 2020

AbstractAutografts and allografts are currently considered the gold standard for grafting surgery; however, to meet the growing demand in fast-aging societies, synthetic biomaterials will play an increasingly important role. Here we report a biodegradable scaffold material composed of recombinant polypeptide based on the human type I collagen alpha 1 chain (RCPhC1) as a source of hydrogel-based graft materials. The flexibility to engineer ideal characteristics for bone grafts was demonstrated. The critical internal isotropic pore structure was generated through a designed thin-layer freeze casting process. The optimized biodegradation rate was controlled by dehydrothermal crosslinking by adjusting the amino acid composition of RCPhC1. As a result, RCPhC1 bone grafts manufactured by a highly scalable streamlined production protocol induced robust regeneration of mature bone tissue while being completely resorbed in pre-clinical animal models.
Cross-cultural adaptation and translation of the Constant Murley Score into Arabic
Authors: Maqdes Ali , Hanna Sager Samir , Bouhamra Ahmed Khaled , Khaja Aliaa F. 
Published: November 2020

Introduction: Shoulder pain is a major disorder of the musculoskeletal system. To the best of our knowledge, there is no documentation of an Arabic version of the shoulder disability and pain measurements. Constant Murley Score (CMS) is one of the standard questionnaires for clinical practice and research. The aim of this research centred around the evaluation of the Arabic Constant Murley Score and subsequently assessing the reliability and validity in comparison to disabilities of the arm, shoulder, and hand (DASH).Methods: Hundred and twenty five patients took part in this research. We did the internal consistency tests with Cronbach’s alpha. Intra-correlation coefficient, convergent validity, convergent construct validity, responsiveness, and floor and ceiling effects were also calculated.Results: Principal component analysis showed that the variance was 63.31% with a factor range of 0.42–0.85, which fulfils the uni-dimensionality criterion. Also, the Arabic CMS correlated negatively with the DASH score (−0.82,p < 0.001). The Arabic version of CMS was consistent with Cronbach’s alpha of 0.74. With Inter Class Correlation Coefficient (ICC) = 0.83 it also showed a very good test-retest reliability.Conclusion: Ours is the first translation and cross-cultural adaptation of the CMS into Arabic. Important evidences of validity were tested such as uni-dimensionality, convergent validity, and internal consistency. Results demonstrate an acceptable Cronbach’s alpha of 0.74, ICC = 0.830 indicating excellent reliability and a strong correlation of the Arabic CMS with the DASH score (r = −0.820). Overall, the Arabic version of CMS is a good and reliable diagnostic tool for patients experiencing shoulder pain.
Choosing an Effective and Safe Direct Aspiration Setup for Tortuous Anatomy in Acute Ischemic Stroke: In vitro Study in a Physiological Flow Model
Authors: Madjidyar Jawid , Nerkada Lars , Larsen Naomi , Wodarg Fritz , Hensler Johannes , Jansen Olav 
Published: November 2020

Purpose A direct aspiration first pass technique (ADAPT) is an effective thrombectomy option in patients with acute ischemic stroke. Balloon guide catheters (BGC) seem to improve the efficacy of stent retrievers and ADAPT. The last generation 6F aspiration catheters require 9F BGCs, which are rigid devices that are challenging to position in a tortuous anatomy. In this experimental study the efficacy of 6F ADAPT alone and 5F ADAPT combined with 8F BGC was evaluated.
Materials and Methods Either a fibrin rich (white) clot or an RBC rich (red) clot was placed in the M1 segment of a transparent silicon phantom. Physiological hemodynamic conditions were maintained. The clots were retrieved by 6F aspiration catheter via 8F long sheath or 5F aspiration catheter via a flexible 8F BGC. Thrombectomy was performed under direct visual control. The primary endpoints were the number of passes and the number of distal emboli.
Results Ten experiments were made with each clot model and thrombectomy technique (n = 40). Full recanalization could be achieved in every experiment. First pass mTICI 3 could be achieved by 6F ADAPT in 80 % of red clots and 90 % of white clots. Distal emboli were caused in 10 % and 20 %, respectively. When using 5F ADAPT combined with BGC, a first pass mTICI 3 rate of 90 % in red clots and 100 % in white clots could be achieved. A 10 % rate of distal emboli occurred in both groups. In almost all experiments (both techniques), the thrombi clogged the aspiration catheter. No statistically significant differences could be found between the techniques and clot models.
Conclusion 6F ADAPT without BGC was as effective as 5F ADAPT combined with a flexible 8F BGC, with both techniques showing high first-pass recanalization rates and low distal emboli rates. Especially in the case of a tortuous anatomy, these setups should be considered as alternatives to a rigid 9F BGC. The thrombus compositions seemed to be irrelevant in this setting.
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Serum Levels of Beta-2 Microglobulin in Rheumatoid Arthritis Patients and its Relationship with Disease Activity: Can it be used as a Disease Activity Marker?
Authors: Dinçer Ayşe Bahar Keleşoğlu , Torgutalp Murat , Yayla Müçteba Enes , Gülöksüz Emine Gözde Aydemir , Sezer Serdar , Yurteri Emine Uslu , Okatan Ilyas Ercan , Turgay Murat , Kınıklı Gülay , Ateş Aşkın 
Published: November 2020

Abstract
Background Beta-2 microglobulin (β2M) is mainly released from activated lymphocytes. Increased serum β2M levels have been shown in autoimmune diseases. The aim of this study was to analyse the serum levels of β2M in rheumatoid arthritis (RA) patients and to evaluate its relationship with disease activity measures.
Material and Methods This cross-sectional study included 137 RA patients, 102 ankylosing spondylitis patients (AS) and 50 healthy controls (HC). To assess the disease activity of RA patients, the 28-joint Disease Activity Score-Erythrocyte Sedimentation Rate (DAS28-ESR), the 28-joint Disease Activity Score-C-Reactive Protein (DAS28-CRP), the Simplified Disease Activity Index (SDAI) and the Clinical Disease Activity Index (CDAI) were used. A p value of <0.05 was considered statistically significant.
Results Serum β2M levels were significantly higher in RA patients (2.95±1.19 mg/L) compared with HC (2.21±0.54 mg/L) and AS patients (2.200.58 mg/L) (p<0.001). There was a statistically significant correlation between β2M levels and DAS28-ESR (rs=0.359, p<0.001), DAS28-CRP (rs=0.293, p=0.001), SDAI (rs=0.332, p<0.001) and CDAI (rs=0.291, p=0.001). Serum β2M levels were higher in the RA group with DAS28-ESR ≥3.2 (3.30±1.42 mg/L) than in the DAS28-ESR <3.2 group (2.67±0.87 mg/L) (p=0.002).
Conclusion Our study revealed that serum β2M levels were higher in RA patients than in healthy controls, and, in contrast to other studies, we found positive correlations between β2M levels and RA disease activity measures.
Synthesis of Spirocyclic Piperidines by Radical Hydroarylation
Authors: Spurlin Racheal M. , Harris Amber L. , Jui Nathan T. , Pratt Cameron J. 
Published: November 2020

AbstractReported here are conditions for the construction of spirocyclic piperidines from linear aryl halide precursors. These conditions employ a strongly reducing organic photoredox catalyst in combination with a trialkylamine reductant to achieve formation of aryl radical species. Regioselective cyclization followed by hydrogen-atom transfer affords a range of complex spiropiperidines. This system operates efficiently under mild conditions without the need for toxic reagents or precious metals.
Peroxide-Mediated Oxidative Radical Cyclization to the Quinazolinone System: Efficient Syntheses of Deoxyvasicinone, Mackinazolinone and (±)-Leucomidine C
Authors: Miranda Luis D. , García-Ramírez Jazmín 
Published: November 2020

AbstractAn efficient protocol for obtaining fused quinazolinones through an oxidative free-radical cyclization under metal- and tin-free conditions is described. The oxidative cyclization of various N-3-ω-iodoalkyl derivatives to provide tricyclic systems using dicumyl peroxide as the sole reagent is studied. The method then is employed for the syntheses of 5-, 6-, and 7-membered fused quinazolinone analogues, including the natural products deoxyvasicinone and mackinazolinone. A xanthate-based oxidative radical cascade addition/cyclization process that allows the production of new menthol- and testosterone-quinazolinone conjugates, as well as the first total synthesis of leucomidine C, are also reported.
Facile Access to 3,4-Disubstituted 2H-Chromenes via Domino [4+2] Annulation
Authors: Prasad Sure Siva , Joshi Dirgha Raj , Kim Ikyon 
Published: November 2020

AbstractA highly efficient synthetic route to polysubstituted 2H-chromenes was developed utilizing a domino O-alkylation/intramolecular Horner–Wadsworth–Emmons (HWE) olefination of diarylmethylphosphonates, which were readily accessed via Lewis acid mediated one-pot three-component coupling of aldehydes, phenols, and triethyl phosphite.
Impact of the Extent of Microsurgical Resection in Sphenopetro-clival Meningiomas Trough a Multistaged Approach: A Volumetric Analysis
Authors: Martínez-Pérez Rafael , Tsimpas Asterios , Ganau Mario , Mura Jorge M. 
Published: November 2020

Abstract
Objective Sphenopetroclival meningiomas (SPCMs) represent a challenge for surgical treatment. The authors used an objective volumetric analysis to assess the effect of the grade of resection and different surgical strategies that may affect the outcome of this tumors.
Methods Over a period of 4 years, patients with SPCMs were treated using a middle versus posterior fossa approach, or a two-stage surgery combining both approaches, based on the tumor location in relation to the petrous ridge and tumor volume. Retrospectively, all cases were analyzed with regard to tumor volume, extent of resection (EOR), functional outcome, and complications.
Results Twenty-seven patients with SPCMs met the inclusion criteria, and the mean follow-up was 24.8 months. Eleven patients underwent a two-stage surgery, while 16 patients had their SPCMs resected via a single craniotomy. Mean EOR was 87.6% and gross total resection was achieved in 48% of patients. Patients with greater EOR had better functional outcomes (r = 0.81, p < 0.01). Greater EOR was not accompanied by a significant increase in surgical complications. There was a trend toward lower postoperative volumes and better EOR with our two-stage approach (2.2 vs. 3.2 cm3, p = 0.09; and 94.1 vs. 91.2%, p = 0.49, respectively), without an increase in the rate of complications (18.7 vs. 18.2%, p = 0.5).
Conclusion Staging of the surgical resection of larger tumors may lead to greater EOR, and this strategy should be considered for larger tumors.
Anesthetic Challenges in the Management of Intracranial Aneurysm Clipping in a Patient with Hypertrophic Cardiomyopathy
Authors: Duggal Sakshi , Khurana Priyanka , Ganjoo Pragati , Das Nilima 
Published: November 2020

AbstractAneurysmal surgeries are high-risk procedures due to potential for occurrence of fatal perioperative complications. This risk is exaggerated in the presence of co- existing hypertrophic cardiomyopathy (HCM). It involves asymmetrical hypertrophy of left ventricle with mitral valve dysfunction, leading to left ventricular outflow tract obstruction. Various perioperative factors may precipitate this obstruction resulting in life-threatening consequences. We report the management of a patient with HCM undergoing anterior communicating artery aneurysm clipping and discuss the anesthetic concerns. Comprehensive approach with careful drug selection, vigilant monitoring, and preparedness for complications enabled patient safety and a good neurological outcome.
Monitoring of Unfractionated Heparin in Severe COVID-19: An Observational Study of Patients on CRRT and ECMO
Authors: Streng Alexander S. , Delnoij Thijs S.R. , Mulder Mark M.G. , Sels Jan Willem E.M. , Wetzels Rick J.H. , Verhezen Paul W.M. , Olie Renske H. , Kooman Jeroen P. , van Kuijk Sander M.J. , Brandts Lloyd , ten Cate Hugo , Lorusso Roberto , van der Horst Iwan C.C. , van Bussel Bas C.T. , Henskens Yvonne M.C. 
Published: November 2020

Abstract
Objective Severe cases of coronavirus disease 2019 (COVID-19) can require continuous renal replacement therapy (CRRT) and/or extracorporeal membrane oxygenation (ECMO). Unfractionated heparin (UFH) to prevent circuit clotting is mandatory but monitoring is complicated by (pseudo)-heparin resistance. In this observational study, we compared two different activated partial thromboplastin time (aPTT) assays and a chromogenic anti-Xa assay in COVID-19 patients on CRRT or ECMO in relation to their UFH dosages and acute phase reactants.
Materials and Methods The aPTT (optical [aPTT-CS] and/or mechanical [aPTT-STA] clot detection methods were used), anti-Xa, factor VIII (FVIII), antithrombin III (ATIII), and fibrinogen were measured in 342 samples from 7 COVID-19 patients on CRRT or ECMO during their UFH treatment. Dosage of UFH was primarily based on the aPTT-CS with a heparin therapeutic range (HTR) of 50–80s. Associations between different variables were made using linear regression and Bland–Altman analysis.
Results Dosage of UFH was above 35,000IU/24 hours in all patients. aPTT-CS and aPTT-STA were predominantly within the HTR. Anti-Xa was predominantly above the HTR (0.3–0.7 IU/mL) and ATIII concentration was >70% for all patients; mean FVIII and fibrinogen were 606% and 7.5 g/L, respectively. aPTT-CS correlated with aPTT-STA (r
2 = 0.68) with a bias of 39.3%. Correlation between aPTT and anti-Xa was better for aPTT-CS (0.78 ≤ r
2 ≤ 0.94) than for aPTT-STA (0.34 ≤ r
2 ≤ 0.81). There was no general correlation between the aPTT-CS and ATIII, FVIII, fibrinogen, thrombocytes, C-reactive protein, or ferritin.
Conclusion All included COVID-19 patients on CRRT or ECMO conformed to the definition of heparin resistance. A patient-specific association was found between aPTT and anti-Xa. This association could not be explained by FVIII or fibrinogen.
Diagnostic Yield of Multiplex PCR Method in Cerebrospinal Fluid for the Diagnosis of Purulent Meningitis in Children
Authors: Zhao Jing-Li , Hua Chun-Zhen , Xie Yong-Ping , Pan Yan-Xiang , Hu Bo-Fei , Wang Wei-Jian , He Xiu 
Published: November 2020

Abstract
Objective To evaluate the diagnostic yield of the multiplex polymerase chain reaction (PCR) method in cerebrospinal fluid (CSF) for the diagnosis of purulent meningitis (PM) in children.
Methods PM was diagnosed according to the European Society for Clinical Microbiology and Infectious Diseases guideline (2016). Patients with PM between May 2015 and October 2018 were included. The multiplex PCR method was used to detect eight common identified bacteria in PM. Its sensitivity and specificity were compared with bacteria culture.
Results A total of 106 cases were enrolled. Pathogenic bacteria were identified in 27 (25.5%) cases by culture and in 37 (34.9%) cases by multiplex PCR assay. The top three bacteria were Streptococcus pneumoniae, Escherichia coli K1, and Streptococcus agalactiae. When using culture as the gold standard, the multiplex PCR assay showed a sensitivity of 100, 88.9, and 75.0% for S. agalactiae, S. pneumoniae, and E. coli K1, respectively, and a specificity of more than 91.3% for all three bacteria. For detectable bacteria, the positive rate of the multiplex PCR assay (36.6%, 37/101) was significantly higher than that of the bacteria culture (21.8%, 22/101). When combining the two methods, etiology was identified in 42.5% (45/106) of the patients.
Conclusion Streptococcus pneumoniae, E. coli K1, and S. agalactiae were the predominant pathogens causing pediatric PM. As a rapid method with high sensitivity and specificity, the multiplex PCR assay in CSF could be used as an adjunctive approach with bacteria culture for the pathogen identification of PM.