bluuebunny/crossref_metadata_2025_split huggingface dataset:
VAMP-2 Is a Surrogate Cerebrospinal Fluid Marker of Alzheimer-related Cognitive Impairment in Adults With Down Syndrome
Authors: Lleó Alberto , Carmona-Iragui Maria , Videla Laura , Fernández Susana , Benejam Bessy , Pegueroles Jordi , Barroeta Isabel , Altuna Miren , Valldeneu Silvia , Xiao Mei-Fang , Xu Desheng , Núñez-Llaves Raúl , Querol-Vilaseca Marta , Sirisi Sònia , Bejanin Alexandre , Iulita M. Florencia , Clarimón Jordi , Blesa Rafael , Worley Paul , Alcolea Daniel , Fortea Juan , Belbin Olivia 
Published: March 2021

Abstract
Background. There is an urgent need for objective markers of Alzheimer’s disease (AD)-related cognitive impairment in people with Down syndrome (DS) to improve diagnosis, monitor disease progression and assess response to disease-modifying therapies. Previously, GluA4 and Neuronal Pentraxin 2 (NPTX2) showed limited potential as cerebrospinal fluid (CSF) markers of cognitive impairment in adults with DS. Here we compare the CSF profile of a panel of synaptic proteins (Calsyntenin-1, Neuroligin-2, Neurexin-2A, Neurexin-3A, Syntaxin-1B, Thy-1, VAMP-2) to that of NPTX2 and GluA4 in a large cohort of subjects with DS across the preclinical and clinical AD continuum and explore their correlation with cognitive impairment. Methods. We quantified the synaptic panel proteins by selected reaction monitoring in CSF from 20 non-trisomic cognitively normal controls (mean age 44) and 80 adults with DS grouped according to clinical AD diagnosis (asymptomatic, prodromal AD or AD dementia). We used regression analyses to determine CSF changes across the AD continuum and explored correlations with age, global cognitive performance (CAMCOG), episodic memory (modified cued-recall test; mCRT) and CSF AD biomarkers, CSF Aβ42:40 ratio, CSF Aβ1-42 and CSF p-tau. P-values were adjusted for multiple testing. Results. In adults with DS, VAMP-2 was the only synaptic protein to correlate with episodic memory (delayed recall adj.p=.04) and age (adj.p=.0008) and was the best correlate of CSF Aβ42:40 (adj.p=.0001) and CSF p-tau (adj.p<.0001). Compared to controls, mean VAMP-2 levels were lower in asymptomatic adults with DS only (adj.p=.02). CSF levels of Neurexin-3A, Thy-1, Neurexin-2A, Calysntenin-1, Neuroligin-2, GluA4 and Syntaxin-1B all strongly correlated with NPTX2 (p<.0001), which was the only synaptic protein to show reduced CSF levels in DS at all AD stages compared to controls (adj.p<.002). Conclusion. CSF VAMP-2 represents a promising objective surrogate marker of cognitive failure in DS. VAMP-2 also has potential for use in AD clinical trials as a measure of synapse engagement and therapeutic response that does not directly measure the drug target (typically Aβ and tau).
Morphological and Ecological Features of Some Nematodes of the Genus Rhabdochona in Marinka Obtained From Fergana Valley, Uzbekistan
Authors: Kuchboev Abdurakhim , Najmidinov Eldor Kh , Mukhamediev Muzaffar A , Karimova Rokhatoy R , Yildiz Kader 
Published: March 2021

Abstract
The aim is to study the morphological and ecological features of some nematode species of the genus Rhabdochona parasites of marinka fish in the Fergana Valley, Uzbekistan. Rhabdocona gnedini, Rhabdochona denudata and Rhabdocona hellichi turkestanica were detected as 5.3%, 7.9% and 3.7%, respectively. According to the Authors’ knowledge, Rh. hellichi turkestanica was recorded in Uzbekistan and Central Asian republics for the first time. Rhabdocona spp. were only detected in the intestine of marinkas lived in the mountain rivers Rezaksay, Chodaksay and small tributaries of the Syrdarya river in western Fergana. Some abiotic factors such as the flow rate, water temperature and high content of dissolved oxygen in it, as well as the nutritional characteristics of the fish can be most important factors to spread of Rh.denudata, Rh. gnedini, Rh. hellichi turkestanica in marinkas from mountain rivers of the Fergana Valley.
FDG PET/CT to Detect Bone Marrow Involvement in the Initial Staging of Patients With Aggressive Non-Hodgkin Lymphoma: Results From the Prospective, Multicenter PETAL and OPTIMAL&gt;60 Trials
Authors: Kaddu-Mulindwa Dominic , Altmann Bettina , Held Gerhard , Angel Stephanie , Stilgenbauer Stephan , Thurner Lorenz , Bewarder Moritz , Schwier Maren , Pfreundschuh Michael , Löffler Markus , Menhart Karin , Grosse Jirka , Ziepert Marita , Herrmann Ken , Dührsen Ulrich , Hüttmann Andreas , Barbato Francesco , Poeschel Viola , Hellwig Dirk 
Published: March 2021

Abstract
PURPOSEFluorine-18 fluorodeoxyglucose positron emission tomography combined with computed tomography (FDG PET/CT) is the standard for staging aggressive non-Hodgkin lymphoma (NHL). Limited data from prospective studies is available to determine whether initial staging by FDG PET/CT provides treatment-relevant information of bone marrow (BM) involvement (BMI) and thus could spare BM biopsy (BMB).METHODSPatients from PETAL (NCT00554164) and OPTIMAL>60 (NCT01478542) with aggressive B-cell NHL initially staged by FDG PET/CT and BMB were included in this pooled analysis. The reference standard to confirm BMI included a positive BMB and/or FDG PET/CT confirmed by targeted biopsy, complementary imaging (CT or magnetic resonance imaging), or concurrent disappearance of focal FDG-avid BM lesions with other lymphoma manifestations during immunochemotherapy.RESULTSAmong 930 patients, BMI was detected by BMB in 85 (prevalence 9%) and by FDG PET/CT in 185 (20%) cases, for a total of 221 cases (24%). All 185 PET-positive cases were true positive, and 709 of 745 PET-negative cases were true negative. For BMB and FDG PET/CT, sensitivity was 38% (95% confidence interval [CI]: 32%-45%) and 84% (CI: 78%-88%), specificity 100% (CI: 99%-100%) and 100% (CI: 99%-100%), positive predictive value 100% (CI: 96%-100%) and 100% (CI: 98%-100%), and negative predictive value 84% (CI: 81%-86%) and 95% (CI: 93%-97%), respectively. In all of the 36 PET-negative cases with confirmed BMI patients had other adverse factors according to IPI that precluded a change of standard treatment. Thus, the BMB would not have influenced the patient management.CONCLUSIONIn patients with aggressive B-cell NHL, routine BMB provides no critical staging information compared to FDG PET/CT and could therefore be omitted. Trial registration numberPETAL study, NCT00554164, registered 6 November 2007OPTIMAL>60 study, NCT01478542, registered 23 November 2011
Late-onset X-linked Chronic Granulomatous Disease in a Female Carrier: Therapeutic Role of Interferon-γ and Hematopoietic Stem Cell Transplantation
Authors: Trevisan Matteo , Kang Elizabeth , Salton Francesco , Naviglio Samuele , Ruaro Barbara , Confalonieri Paola , Valencic Erica , Corin Kelly , Parta Mark , Notarangelo Luigi Daniele , Tommasini Alberto , Malech Harry Lewis , Confalonieri Marco 
Published: March 2021

Abstract
X-linked Chronic Granulomatous Disease (CGD) is a rare inherited immunodeficiency characterized by early life-threatening infections from bacteria and fungi in male children. Female carriers of X-linked CGD usually do not develop any manifestations of the disease, yet in rare cases they may present with CGD-related manifestations due to skewed X chromosome inactivation, even in advanced age. Here, we report the case of a 49-year-old woman with no history of previous frequent or severe infections, who presented acutely with life-threatening bilateral pneumonia caused by Nocardia asteroides and was eventually diagnosed with late-onset X-linked CGD due to skewed X chromosome inactivation in white blood cells. Treatment with interferon-γ as a rescue therapy resulted in normalization of the intensity of the oxidative burst in the residual positive cells and resolution of the infection, which was otherwise resistant to conventional treatments. After discharge, however, recurrent severe pulmonary infections despite prophylactic treatments as well as appearance of granulomatous colitis led to considering definitive treatment. Hematopoietic stem cell transplantation from unaffected HLA-identical brother using a non-myeloablative conditioning protocol with intravenous busulfan followed by high-dose peripheral blood stem cell graft and post-transplant cyclophosphamide was successfully performed. After three years of follow-up, white blood cell chimerism remained stable with about 60% donor cells in the myeloid lineage, with no further infections and no recurrence of inflammatory bowel disease.
Effect of Tourniquet Application on Postoperative Outcomes in Minimally Invasive Surgery for Intra-articular Calcaneus Fractures
Authors: Zaid Hamood H.G. , Di Wu , Yang Rufei , Zhao Tianyuan , yang Maowei 
Published: March 2021

Abstract
Background: Tourniquets are commonly used during foot and ankle surgery to provide a bloodless operative field and for the sake of the surgeon`s comfort, despite the potential risks associated with it. This study was performed to compare postoperative outcomes of tourniquet-assisted to non-tourniquet-assisted operative fixation of calcaneal fractures.Methods: A total of 131 patients with closed calcaneal fracture who underwent minimally invasive surgery of calcaneal fractures between March 2015 and December 2018 were reviewed retrospectively. Patients for whom a tourniquet was used intraoperatively (n = 62) were compared to those without (n = 69). Operating time and visualization, blood loss, postoperative pain according to visual analogue scale (VAS), the American Orthopaedic Foot & Ankle Society (AOFAS) Ankle-Hindfoot score, and hospital length of stay were recorded for all the patients.Results: Statistical analysis of the results showed significant differences between tourniquet and non-tourniquet groups in the mean operation time, visibility of the surgical field, mean estimated intraoperative and postoperative blood loss, and mean VAS pain scores 24 H, 48 H, 72 H postoperatively (P < 0.05), whereas no significant difference between two groups in the mean Serum CPK levels, post-operative swelling, mean length of stay, AOFAS score, wound and fracture healing time, and the mean time for return to work.Conclusion: Our study demonstrated that tourniquet application during minimally invasive surgery of calcaneal fractures can significantly shorten the operation time, improve surgical visualization, and reduce intraoperative blood loss. However, adverse events associated with the use of tourniquet include increased postoperative pain, and more amount of postoperative bleeding. Due to higher postoperative pain and more amount of postoperative bleeding, more attention should be paid on the postoperative phase for those who tourniquet was used. The surgeon's decision to use a tourniquet during calcaneal fractures surgery should be carefully considered.
Effect of Mineralocorticoid Receptor Antagonists on Secondary Prevention of Cardiomyopathy Progression in Childhood Cancer Survivors
Authors: Wilson-Raya Averi E. , Bowen Trey , Bosler Teresa , Hynan Linda S. , Bowers Daniel C. , Cochran Cindy J. , Lee Simon C , Orlino Angela M. , Zaha Vlad 
Published: March 2021

Abstract
BACKGROUNDThe effect of mineralocorticoid receptor antagonists (MRA) on secondary prevention of late anthracycline-induced cardiomyopathy in childhood cancer survivors is unknown, while other heart failure therapies showed only transient effect. This study sought to assess whether MRA’s may prevent the left ventricular systolic dysfunction caused by latent anthracycline cardiotoxic effects.METHODSCross-sectional, proof of concept study of adult survivors of childhood cancer followed up at the After Cancer Experience and Cardio-Oncology clinics, UT Southwestern Medical Center, after completing anthracycline treatment at least two years prior to this study, in the prior decade. Cross-sectional symptom questionnaires administered during the study and retrospective clinical, laboratory, and imaging data extracted from the electronic medical records were analyzed in 3 groups of patients: on MRA therapy, on heart failure therapy regimen without MRA, and not on therapy for heart failure.RESULTSOf 105 enrolled, 67 patients completed the study. At baseline, the MRA group demonstrated lower LVEF (46% (30-51), n=8 MRA therapy vs 61% (57-63), n=46 no therapy; p<0.01) and higher ESV (59mL (41-90), n=8 MRA therapy vs 36mL (29-43), n=40 no therapy, p<0.05). The MRA group reported a decreased ability to walk one block compared with the non-MRA and no therapy groups (p=0.013). Administration of MRA resulted in a significant improvement in LVEF (52% (34-56), p=0.031 compared to baseline).CONCLUSIONSMRA administration as single drug therapy or in combination with standard of care heart failure therapy may prevent the progression of left ventricular dysfunction in childhood cancer survivors with late anthracycline-induced cardiomyopathy.
The Staged Treatment for Tibial Plateau Fractures and the Reconstruction of Lateral Column With Autogenous Iliac Bone: an Efficacy Analysis Report
Authors: Li Dong , Liang Xiao , Xi Kun , Zhao Bin , Hou Fushan 
Published: March 2021

Abstract
BackgroundComplications in treating comminuted tibial plateau fractures with extensive soft tissue damage are common. In this study, we discussed the effect of staged treatment in the reconstruction of the lateral column with autogenous iliac bone using case follow-up.MethodsA retrospective analysis of 18 patients with comminuted tibial plateau fractures and extensive soft tissue damage from October 2016 to February 2020 who underwent staged treatment in our hospital. After the soft tissue damage repair, a large autologous iliac bone was used to reconstruct the lateral column of the tibial plateau.ResultsAll 18 patients were followed up over the course of 8-40 months, with an average of 23.44 months. All patients reported zero postoperative infection, skin and soft tissue necrosis, and loosening/breakage of the internal fixation. Regular postoperative review revealed that all patients achieved complete bony union, as evidenced by X-ray film, at 6 months after operation. Knee function (HSS) scores averaged 86.72 points at 1 year after operation; 15 people with 85 points or more, 2 people with 70-84 points, and one with 68 points. The excellent rate, according to HSS was 90%.Conclusions﻿Complex tibial plateau fractures with extensive soft tissue damage can be effectively remedied with a staged treatment, wherein a lateral column reconstruction is performed using a large iliac bone.
A Unifying Model to Estimate Thermal Tolerance Limits in Ectotherms Across Static, Dynamic and Fluctuating Exposures to Thermal Stress
Authors: Jørgensen Lisa Bjerregaard , Malte Hans , Ørsted Michael , Klahn Nikolaj Andreasen , Overgaard Johannes 
Published: March 2021

Abstract
Temperature tolerance is critical for defining the fundamental niche of ectotherms and researchers classically use either static (exposure to a constant temperature) or dynamic (ramping temperature) assays to assess tolerance. The use of different methods complicates comparison between studies and here we present mathematical model (and R-scripts) to reconcile thermal tolerance measures obtained from static and dynamic assays. Our model uses input data from several static or dynamic experiments and is based on the well-supported assumption that thermal injury accumulation rate increases exponentially with temperature (recently re-introduced as Thermal Tolerance Landscapes). The model also assumes thermal stress at different temperatures to be additive and using experiments with Drosophila melanogaster, we validate these central assumptions by demonstrating that heat injury attained at different heat stress intensities and durations is additive. In a separate experiment we demonstrate that our model can accurately describe injury accumulation during fluctuating temperature stress and further we validate the model by successfully converting literature data of ectotherm heat tolerance (both static and dynamic assays) to a single, comparable metric (the temperature tolerated for 1 hour). The model presented here has many promising applications for the analysis of ectotherm thermal tolerance and we also discuss potential pitfalls that should be considered and avoided using this model.
Prodigiosin-functionalized Lactobacillus acidophilus ghost: A bioinspired combination against colorectal cancer cells
Authors: Saleh Nessrin , Mahmoud Hoda , Eltaher Hoda , Helmy Maged , El-Khordagui Labiba , Hussein Ahmed 
Published: March 2021

Abstract
Lactobacillus acidophilus ghosts (LAGs) with the unique safety of a probiotic, inherent tropism for colon cells and multiple bioactivities offer great promise as drug carrier for colon targeting. We report herein on a novel bioinspired drug delivery system against colorectal cancer (CRC) cells based on LAGs functionalized with prodigiosin (PG), a proapoptotic bacterial metabolite. LAGs were prepared by a chemical method and highly purified by density gradient centrifugation. Multiple microscopic and staining techniques characterized LAGs by a relatively small size, size uniformity, a relatively large internal volume devoid of cytoplasmic and genetic materials and an intact negatively charged envelop. PG was highly bound to LAGs cell wall, generating a physiologically stable bioactive entity (PG-LAGs) active against HCT116 CRC cells at the cellular and molecular levels. Cell viability data underlined cytotoxicity of PG and LAGs and LAGs-induced enhancement of PG selectivity for HCT116 cells. Combination and Dose reduction indices anticipating dose reduction of PG and LAGs. Molecularly, PG-LAGs significantly modulated the expression of apoptosis-related biomarkers, caspase 3, P53 and BCL2, in favor of cytotoxicity against HCT116 cells relative to PG and 5-fluorouracil. Accordingly, LAGs offer promise as novel drug carrier for targeted colon delivery and PG-LAGs may bring therapeutic benefits in colorectal carcinoma.
Polygenic scores for handedness and their association with asymmetries in brain structure
Authors: Ocklenburg Sebastian , Metzen Dorothea , Schlüter Caroline , Fraenz Christoph , Arning Larissa , Streit Fabian , Güntürkün Onur , Kumsta Robert , Genc Erhan 
Published: March 2021

Abstract
Handedness is the most widely investigated motor preference in humans. The genetics of handedness and especially the link between genetic variation, brain structure and right-left preference have not been investigated in detail. Recently, several well-powered genome-wide association studies (GWAS) on handedness have been published, significantly advancing the understanding of the genetic determinants of left- and right-handedness. In the present study, we estimated polygenic scores (PGS) of handedness based on the latest GWAS by de Kovel and Francks (2019) in an independent validation cohort (n = 296). PGS reflect the sum effect of trait-associated alleles across many genetic loci. For the first time, we could show that these GWAS-based PGS can significantly predict individual handedness lateralization quotients in an independent validation cohort. Additionally, we investigated whether handedness-derived polygenic scores can predict asymmetries in gray matter macrostructure across the whole brain determined using magnetic resonance imaging. Our results indicate that none of these predictions reached significance after correction for multiple comparisons. This indicates that the genetic determinants of handedness are only weakly associated with structural asymmetries in gray matter. Other brain phenotypes may link genetic variation to handedness.
Rate of losing energy in Quantum Redshift
Authors: Kalhor Bahram , Mehrparvar Farzaneh , Kalhor Behnam 
Published: March 2021

Abstract
The paper simulates the losing energy of the electromagnetic waves in a non-expansion space and no gravitational Redshift. We use the distance and Redshift of 93,060 nearby space objects, including stars, quasars, white dwarfs, and carbon stars, for obtaining the rate of losing the energy of their waves during traveling in space. Quantum Redshift disagrees expansion of space and describes Redshift by losing the energy of electromagnetic waves over time. In the Quantum Redshift, regardless of the material and type of the space objects (stars, quasars, white dwarfs, and carbon stars), the Redshift depends on the distance and temperature of the space objects, and the temperature of space. We have used SIMBAD Astronomical Database. We have retrieved this information from almost 2,200,000 records. The objects' temperature is between 671 and 99,575 K. The distance of the objects is between 413.13 and 0.5 (mas). The paper obtains the average rate of losing the waves' energy for different objects in different distances. The results show that by increasing the distance of space objects, the rate of losing the energy of their electromagnetic waves will be decreased. The paper inspires investigating the expansion space theory by the Quantum Redshift.
BCMA targets bispecific fusion protein for induction of NK cell activity against multiple myeloma
Authors: Xu Wei , Wang Yang , Li Hui , Wang Min , Zhang Juan 
Published: March 2021

Abstract
PurposeMultiple myeloma (MM) is the second most common hematological malignancy, and B-cell maturation antigen (BCMA) is a highly regarded target of MM research. In tumors, the natural killer (NK) cell receptor NK group 2, member D (NKG2D), and its ligand MHC class I-related chain A (MICA) play important roles in immune surveillance and killing. We developed a bispecific fusion protein (BFP) that targeted NKG2D and BCMA, which may be useful for the MM therapeutic market.MethodsThe Homo MICA extracellular domains (hMICA) α1-3 or α1-2 were fused to the end of the single chain antibody (ScFv) 2A9 with the flexible linker (G4S), which formed 2A9-MICA and 2A9-MICAα1-2. These were further identified using sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) and western blotting (WB). The dual-targeting specificity was characterized using Surface Plasmon Resonance (SPR) technology and a flow cytometry assay. In addition, a cytotoxicity assay showed that the design of BFP mediated the lysis of MM cells. Further, in MM-bearing nude mice, the anti-tumor effect and the ability to activate NK cells within tumor tissues of BFP were verified.ResultsCompared with 2A9-MICA, 2A9-MICAα1-2 had a stronger affinity to BCMA and NKG2D, which mediated cytotoxicity of NK effector cells against MM cells. In vivo, 2A9-MICAα1-2 showed superior anti-MM efficacy, significantly reduced malignancy, effectively activated CD56+TNF-α+ NK cells, and promoted immune infiltration within the tumor environment.ConclusionAfter we evaluated aspects of 2A9-MICA and 2A9-MICAα1-2 comprehensively, we concluded that 2A9-MICAα1-2 deserves further study and investigation, and it provides a possible strategy for immunotherapy that targets MM.