bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Impact of Helminth Infection on the Incidence of Metabolic Syndrome: A Systematic Review and Meta-Analysis
Authors: Rennie Claire , Fernandez Ritin , Donnelly Sheila , McGrath Kristine CY 
Published: August 2021

BackgroundThere are a growing number of publications that report an absence of inflammatory based disease among populations that are endemic to parasitic worms (helminths) demonstrating the ability of these parasites to potentially regulate human immune responses. The aim of this systematic review and meta-analysis was to determine the impact of helminth infection on metabolic outcomes in human populations.MethodsUsing PRISMA guidelines, six databases were searched for studies published up to August 2020. Random effects meta-analysis was performed to estimate pooled proportions with 95% confidence intervals using the Review Manager Software version 5.4.1.ResultsFourteen studies were included in the review. Fasting blood glucose was significantly lower in persons with infection (MD -0.22, 95% CI -0.40- -0.04, P=0.02), HbA1c levels were lower, although not significantly, and prevalence of the metabolic syndrome (P=0.001) and type 2 diabetes was lower (OR 1.03, 95% CI 0.34-3.09, P&lt;0.0001). Infection was negatively associated with type 2 diabetes when comparing person with diabetes to the group without diabetes (OR 0.44, 95% CI 0.29-0.67, P=0.0001).ConclusionsWhile infection with helminths was generally associated with improved metabolic function, there were notable differences in efficacy between parasite species. Based on the data assessed, live infection with S. mansoni resulted in the most significant positive changes to metabolic outcomes.Systematic Review RegistrationWebsite: PROSPERO Identified: CRD42021227619.
Nasal Administration of Anti-CD3 Monoclonal Antibody (Foralumab) Reduces Lung Inflammation and Blood Inflammatory Biomarkers in Mild to Moderate COVID-19 Patients: A Pilot Study
Authors: Moreira Thais G. , Matos Kimble T. F. , De Paula Giovana S. , Santana Thais M. M. , Da Mata Raquel G. , Pansera Fernando C. , Cortina Andre S. , Spinola Marcelle G. , Baecher-Allan Clare M. , Keppeke Gerson D. , Jacob Jules , Palejwala Vaseem , Chen Karen , Izzy Saef , Healey Brian C. , Rezende Rafael M. , Dedivitis Rogerio A. , Shailubhai Kunwar , Weiner Howard L. 
Published: August 2021

BackgroundImmune hyperactivity is an important contributing factor to the morbidity and mortality of COVID-19 infection. Nasal administration of anti-CD3 monoclonal antibody downregulates hyperactive immune responses in animal models of autoimmunity through its immunomodulatory properties. We performed a randomized pilot study of fully-human nasal anti-CD3 (Foralumab) in patients with mild to moderate COVID-19 to determine if its immunomodulatory properties had ameliorating effects on disease.MethodsThirty-nine outpatients with mild to moderate COVID-19 were recruited at Santa Casa de Misericordia de Santos in Sao Paulo State, Brazil. Patients were randomized to three cohorts: 1) Control, no Foralumab (n=16); 2) Nasal Foralumab (100ug/day) given for 10 consecutive days with 6 mg dexamethasone given on days 1-3 (n=11); and 3) Nasal Foralumab alone (100ug/day) given for 10 consecutive days (n=12). Patients continued standard of care medication.ResultsWe observed reduction of serum IL-6 and C-reactive protein in Foralumab alonevs. untreated or Foralumab/Dexa treated patients. More rapid clearance of lung infiltrates as measured by chest CT was observed in Foralumab and Foralumab/Dexa treated subjectsvs. those that did not receive Foralumab. Foralumab treatment was well-tolerated with no severe adverse events.ConclusionsThis pilot study suggests that nasal Foralumab is well tolerated and may be of benefit in treatment of immune hyperactivity and lung involvement in COVID-19 disease and that further studies are warranted.
Biomechanical Properties of 3D-Printed Cervical Interbody Fusion Cage With Novel SF/nHAp Composites
Authors: Chen Shuang , Meng Yi , Wu Guozhi , Liu Zhize , Lian Xiaodong , Hu Jianyu , Yang Dongfang , Zhang Guiqi , Li Kun , Zhang Hao 
Published: August 2021

Anterior cervical discectomy and fusion (ACDF) is a commonly used surgical method for the treatment of cervical spondylosis. As ACDF surgery is widely used in clinics, identifying suitable materials to design and prepare cervical interbody fusion cages is a hot research topic. Here, we describe a new three-dimensional (3D) printing approach to create stretchable and tough silk fibroin/nano-hydroxyapatite (SF/nHAp) composites with tunable mechanical properties. The compressive strength of the novel composites with biomimetic structure could reach more than 128 MPa. More importantly, the composites were prepared using 30% silk fibroin and 70% hydroxyapatite, a composition similar to the human bone tissue. Finite element analysis results indicate that the stress distribution of SF/nHAp composite cervical interbody fusion cages in vivo is more uniform than that of commercial Ti alloy cages. This study evaluates the effectiveness of SF/nHAp composites for application in cervical interbody fusion cages and in the field of bone tissue engineering.
Exploration of Nonlinear Optical Properties of Triphenylamine-Dicyanovinylene Coexisting Donor-π-Acceptor Architecture by the Modification of π-Conjugated Linker
Authors: Khan Muhammad Usman , Khalid Muhammad , Asim Sumreen , Momina  , Hussain Riaz , Mahmood Khalid , Iqbal Javed , Akhtar Muhammad Nadeem , Hussain Amjad , Imran Muhammad , Irfan Ahmad , Ali Akbar , Rehman Muhammad Fayyaz ur , Jiang Yang , Lu Changrui 
Published: August 2021

High-tech electronic, optics, and storage devices require organic compounds with nonlinear optical (NLO) properties. This study designed D-π-A based dyes with donor triphenylamine (TPA) and acceptor dicyanovinylene (DCV) species by structurally modifying π-conjugated linkers. Our density functional theory (DFT) computations analyzed the impact of structural variations on the nonlinear optical (NLO) response of newly designed dyes. The B3LYP/6-31G(d,p) level determined the quantic chemical insights: frontier molecular orbital (FMOs), natural bond orbitals (NBOs), and nonlinear optical (NLO) properties of the designed dyes (DPTM-1 to DPTM-12). UV-Vis analysis based on the TD-DFT/CAM-B3LYP/6-311+G(d,p) level explored the optoelectronic properties. DPTM-1 and DPTM-5 showed the highest red-shifted absorption band at 519 and 506 nm. NBO analysis shows that DPTM-1 to DPTM-12 dyes have positive values for all donors (D) and π-spacers but negative values for acceptors (A). The π-spacers act as a conveyer between donor and acceptor moieties; thus, electrons were transferred smoothly from D to A units, which resulted in a charge separation state. Our calculations show the extent of NLO response in terms of electronic transitions, polarizability &lt;α&gt;, and first hyperpolarizability (β) values. The highest value of βtotal was 110,509.23 a.u. manifested in DPTM-6 due to 2,5-dimethyloxazole as a second π-linker, twice that of R (66,275.95 a.u.). Also, DPTM-6 and DPTM-8 exhibit the lowest energy band gap of 2.06 and 2.04 eV, respectively. In short, all DPTM-1 to DPTM-12 dyes manifested maximum absorption, lowest energy band gap, greater charge transfer from donor to the acceptor, and better first hyperpolarizability values as compared to the R and showed good NLO response. The present work represents new compounds with remarkable NLO properties and their applications in modern high-tech devices.
Switching to a Dual-Drug Regimen in HIV-Infected Patients Could Be Associated With Macrophage Activation?
Authors: Vassallo Matteo , Durant Jacques , Fabre Roxane , Ticchioni Michel , Lotte Laurene , Sindt Audrey , Puchois Annick , De Monte Anne , Cezar Renaud , Corbeau Pierre , Pradier Christian 
Published: August 2021

Objectives: The aim of this study was to evaluate the effect on immune activation of switching from a triple-drug to a dual-drug regimen in HIV-1 infected patients on successful combination antiretroviral treatment (cART). Immunadapt is a prospective study evaluating the impact of cART simplification on immune activation.Methods: We prospectively collected blood samples in HIV-1 infected patients on stable and successful cART switching from triple to dual regimens as a simplifying strategy. We compared immune activation markers: high sensitivity CRP, IL-1, IL-6, IL-8, IP-10, MCP-1, TNF-alpha, soluble CD14 (sCD14), soluble CD163 (sCD163), lipopolysaccharide binding protein, and D-dimer before cART change and at least 6 months after the switch. Patients were stratified according to low or high risk factors of immune activation (low CD4 nadir, previous AIDS-defining condition or very-low-level viremia during follow-up).Results: From April 2019 to May 2020, 20 subjects were included (mean age 57 years, 25 years since HIV infection, CD4 666 cells/mm3, CD8 766 cells/mm3, CD4/CD8 0.94, CD4 nadir 326 cells/mm3, 15% with AIDS, 18 years on cART, 6 cART regimens received, current cART duration: 56 months). Fourteen patients were prescribed Dolutegravir + Rilpivirine and six received Dolutegravir + Lamivudine. After 6.9 months, a significant sCD163 increase (+ 25.5% vs. + 0.5%, p = 0.02) was observed in subjects with high risk factors, despite maintaining a viral load &lt;50 cp/ml.Conclusion: cART simplification in favor of dual therapy is associated with macrophage activation in patients at risk of immune activation despite sustained virological control. Risk factors should thus be considered before generalizing such strategies.
Predictive Equation for Angle Opening Distance at 750 μm After Laser Peripheral Iridotomy in Primary Angle Closure Suspects
Authors: Gao Xinbo , Zhou Yuying , Zuo Chengguo , Chen Liming , Ren Jiawei , Lin Huishan , Liao Yunru , Gong Haijun , Hu Huanling , Lin Mingkai 
Published: August 2021

Aim: The aim of this study was to investigate the changes in anterior segment parameters as assessed by ultrasound biomicroscopy (UBM) after laser peripheral iridotomy (LPI) and to propose a prediction equation for the width of the angle after LPI.Design: This was a prospective study.Participants: The participants included 100 subjects with primary angle closure suspect (PACS).Methods: Anterior segment UBM parameters were measured, whereas AOD750 was chosen to indicate the width of the angle associated with gonioscopic angle closure, as found in a prior study.Main Outcome Measures: Angle parameters, iris parameters, anterior chamber parameters and ciliary body parameters.Results: All angle parameters increased after LPI, including the mean angle opening distance at 750 μm (AOD750), mean angle opening distance at 500 μm from the scleral spur (AOD500), mean angle opening distance at 750 μm from the scleral spur (AOD750), and mean angle recess area at 750 μm from the scleral spur (ARA750). Among iris parameters and ciliary body parameters, the iris thickness at 2,000 μm (IT2000), iris curvature (IC), and trabecular-ciliary process distance (ICPD) were reduced after LPI. The final equation consisted of four parameters: anterior chamber depth (ACD), iris thickness at 750 μm from the scleral spur (IT750), AOD750, and lens vault (LV). This equation explained 42.7% of the variability in the angle opening indicator AOD750 after LPI, whereas in the plateau iris configuration subgroup, the accuracy of the prediction equation reached the highest a maximum of 68.6%.Conclusions: There was an increase in angle opening and iris flattening after LPI. An equation involving four angle parameters was constructed, this equation which could explained 42.7% of the variability in the angle opening indicator AOD750 after LPI whereas in the plateau iris configuration subgroup, the accuracy of the prediction equation reached a maximum of 68.6%.
An Integrative Approach to Determine 3D Protein Structures Using Sparse Paramagnetic NMR Data and Physical Modeling
Authors: Gaalswyk Kari , Liu Zhihong , Vogel Hans J. , MacCallum Justin L. 
Published: August 2021

Paramagnetic nuclear magnetic resonance (NMR) methods have emerged as powerful tools for structure determination of large, sparsely protonated proteins. However traditional applications face several challenges, including a need for large datasets to offset the sparsity of restraints, the difficulty in accounting for the conformational heterogeneity of the spin-label, and noisy experimental data. Here we propose an integrative approach to structure determination combining sparse paramagnetic NMR with physical modelling to infer approximate protein structural ensembles. We use calmodulin in complex with the smooth muscle myosin light chain kinase peptide as a model system. Despite acquiring data from samples labeled only at the backbone amide positions, we are able to produce an ensemble with an average RMSD of ∼2.8 Å from a reference X-ray crystal structure. Our approach requires only backbone chemical shifts and measurements of the paramagnetic relaxation enhancement and residual dipolar couplings that can be obtained from sparsely labeled samples.
Olfactory Deficits in the Freezing of Gait Phenotype of Parkinson's Disease
Authors: Glover Aliyah , Pillai Lakshmi , Dhall Rohit , Virmani Tuhin 
Published: August 2021

Background: Olfactory dysfunction often occurs before motor onset in Parkinson's disease (PD) and can be detected with the University of Pennsylvania Smell Identification Test (UPSIT). Based on the Braak hypothesis, the olfactory bulb is one of two sites where disease pathology may start and spread to deeper brain structures.Objective: To evaluate whether a specific pattern of odorant identification on the UPSIT discriminated Parkinson's disease patients with and without freezing of gait.Methods: One hundred and twenty four consecutive participants (33 controls, 31 non-freezers, and 60 freezers) were administered the UPSIT. Using the chi-square test, each odorant on the UPSIT was ranked based on the differential ability of freezers and non-freezers to identify them correctly. Using predictive statistics and confusion matrices, the best combination of odorants and a cut-off score was determined.Results: Freezers had a shift toward a more severe hyposmia classification based on age and sex based normative values. The correct identification of nine odors (bubblegum, chocolate, smoke, wintergreen, paint thinner, orange, strawberry, grass, and peanut) was significantly worse in freezers compared to non-freezers. Correctly identifying ≤ 2 out of 3-odorants (bubblegum, chocolate, and smoke) had a 77% sensitivity and 61% specificity for categorizing freezers. The 3-odorant score was not correlated with disease duration, motor or total UPDRS scores, MoCA scores or age at testing. The predictive statistics were similar when sexes were separately categorized.Conclusions: A 3-odorant score helped categorize freezers and non-freezers with similar sensitivity and specificity to short odorant Parkinson's disease identification batteries.
Serotonergic Modulation of Nigrostriatal and Mesolimbic Dopamine and Motor/Exploratory Behaviors in the Rat
Authors: Nikolaus Susanne , Wittsack Hans-Jörg , Antke Christina , Beu Markus , Hautzel Hubertus , Decheva Cvetana , Mamlins Eduards , Mori Yuriko , Huston Joseph P. , Antoch Gerald , Müller Hans-Wilhelm 
Published: August 2021

Purpose:The 5-HT2Areceptor (R) is known to modulate dopamine (DA) release in the mammalian brain. Altanserin (ALT) and 2,5-dimethoxy-4-iodoamphetamine (DOI) act as 5-HT2AR antagonist and agonist, respectively. In the present study, we assessed the effects of ALT and DOI on motor and exploratory behaviors and on D2/3R binding in the rat brain within vivoimaging methods.Methods:D2/3R binding was determined after systemic application of ALT (10 mg/kg) or DOI (0.5 mg/kg) and the respective vehicles [dimethyl sulfoxide (DMSO) and 0.9% saline (SAL)] with [123I]IBZM as a single-photon emission computed tomography (SPECT) radioligand. Anatomical information for the delineation of the target regions was obtained with dedicated small animal MRI. Immediately after 5-HT2AR antagonistic or agonistic treatment, motor/exploratory behaviors were assessed for 45 (ALT) or 30 min (DOI) in an open field. Additional rats underwent behavioral measurements after injection of DMSO or SAL.Results:ALT increased D2/3R binding in the ventral hippocampus relative to vehicle, while DOI augmented D2/3R binding in caudate putamen, frontal cortex, motor cortex, and ventral hippocampus. The 5-HT2AR agonist as well as antagonist decreased parameters of motor activity and active exploration. However, ALT, in contrast to DOI, decreased explorative head–shoulder motility and increased sitting.Conclusions:The regional increases of D2/3R binding after ALT and DOI (90 and 75 min post-challenge) may be conceived to reflect decreases of synaptic DA. The reductions of motor/exploratory activities (min 1–45 and min 1–30 after challenge with ALT and DOI, respectively) contrast the regional reductions of D2/3R binding, as they indicate elevated DA levels at the time of behavioral measurements. It may be concluded that ALT and DOI modulate DA in the individual regions of the nigrostriatal and mesolimbocortical pathways differentially and in a time-dependent fashion.
Vitamin D Deficiency in Children With Vasovagal Syncope Is Associated With Impaired Circadian Rhythm of Blood Pressure
Authors: Zou Runmei , Wang Shuo , Cai Hong , Li Fang , Lin Ping , Wang Yuwen , Wang Cheng 
Published: August 2021

BackgroundVitamin D deficiency is associated with the risk of cardiovascular diseases. We aimed to investigate the serum vitamin D levels in children with vasovagal syncope (VVS) and explore the correlation of vitamin D status and circadian rhythm of blood pressure in VVS pediatric patients.MethodsThis was a retrospective study. 130 syncopal children diagnosed with VVS were included in the study. 110 age and gender matched healthy individuals were enrolled as control. According to serum 25(OH)D levels, VVS patients were divided into vitamin D sufficient group and vitamin D deficient group. Detailed information of VVS children with vitamin D deficiency and sufficiency on demographic data, baseline laboratory testing, echocardiogram, ambulatory blood pressure monitoring, and Holter ECG recording were extracted and analyzed.ResultsVVS children had a higher prevalence of vitamin D deficiency compared with healthy individuals (33.8% vs. 20.0%, P = 0.017). VVS patients with vitamin D deficiency had a higher rate of non-dipper blood pressure (79.5% vs. 59.3%, P = 0.021) and a lower value of square root of mean squared differences of successive normal to normal intervals (rMSSD) (median 107.8 vs. 141.0 ms, P = 0.035) compared with those with vitamin D sufficiency. Logistic regression analysis showed that non-dipper blood pressure was associated with serum 25(OH)D level [OR = 0.979, 95% CI (0.960, 0.999), P = 0.036].ConclusionVVS pediatric patients had a higher prevalence of vitamin D deficiency. VVS children with vitamin D deficiency showed a higher rate of non-dipper blood pressure, suggesting that vitamin D deficiency is correlated with impaired circadian rhythm of blood pressure.
Kampo Medicine Treatment for Advanced Pancreatic Cancer: A Case Series
Authors: Shimizu Masayuki , Takayama Shin , Kikuchi Akiko , Arita Ryutaro , Ono Rie , Ishizawa Kota , Ishii Tadashi 
Published: August 2021

Aims: The present report aims to investigate the use of Kampo medicine for advanced pancreatic cancer patients in order to prolong survival.Methods: We retrospectively reviewed medical records of patients with pancreatic cancer who presented to our Shimizu Clinic from 2000 to 2020. Patients who survived at least twice as long as the initial prognostic estimate were selected and their treatment was reviewed. The Kampo formula and crude drugs were selected according to the Kampo diagnosis and treatment strategy, which included qi and blood supplementation; qi, blood and water smoothing; and inflammation (termed “heat”) and cancer suppression.Results: Ten patients aged 45–80 years (six males and four females) with stage IV advanced cancer were selected. All patients received hozai, which is a tonic formula, of juzentaihoto (JTT) or hochuekkito (HET) decoction. Anti-cancer crude drugs were included in the decoctions of nine patients. At the first visit, the estimated life expectancy for all patients was no more than 1 year; however, treatment with Western and Kampo medicine led to a relatively long survival period of over 2 years. Three patients were still living at the time of this writing, more than 2, 6, and 14 years after treatment initiation.Conclusion: Our results suggest that Kampo medicine may be useful for disease control and supportive care for patients with advanced pancreatic cancer.
HIST2H2BF Potentiates the Propagation of Cancer Stem Cells via Notch Signaling to Promote Malignancy and Liver Metastasis in Colorectal Carcinoma
Authors: Qiu Lei , Yang Xiuwei , Wu Jingyu , Huang Changzhi , Miao Yongchang , Fu Zan 
Published: August 2021

BackgroundGrowing evidence demonstrates that the initiation and progression of colorectal carcinoma (CRC) is related to the presence of cancer stem cells (CSCs). However, the mechanism through which the stem cell features of CRC cells are maintained is poorly understood. In this study, we identified the oncogenic histone cluster 2 H2B family member F (HIST2H2BF) and aimed to investigate the function of upregulated HIST2H2BF expression in maintaining the stem cell features of CRC cells, which accelerate the progression of CRC.MethodsHIST2H2BF expression was quantified using real-time polymerase chain reaction, immunohistochemistry, and western blotting. The correlation between CpG island methylation status and HIST2H2BF re-expression was assessed through bisulfite sequencing polymerase chain reaction, methylation-specific polymerase chain reaction, and 5-Aza-dC treatment. Functional assays were performed on CRC cells and mice to investigate the HIST2H2BF-induced stem cell-like and cancer properties of CRC. Using the Notch pathway inhibitor FLI-06, the regulatory effect of HIST2H2BF on downstream Notch signaling was confirmed.ResultsHIST2H2BF was highly expressed in CRC tissues and cell lines. The reactivation of HIST2H2BF in CRC stems at least in part from the hypomethylated CpG islands. CRC patients with high HIST2H2BF expression have poor survival outcomes. Functional studies have shown that HIST2H2BF promotes CSC phenotype, malignancy, and liver metastasis through the activation of Notch signaling in CRC. Blockage of the Notch pathway reduced the stem cell-like and cancer properties.ConclusionOur study suggests that HIST2H2BF upregulation enhances the CSC phenotype, malignancy, and liver metastasis through the activation of Notch signaling in CRC. These results identified a new perspective on the mechanism by which the stem cell features of CRC cells are maintained and highlighted the potential novel therapeutic targets for CRC.