bluuebunny/crossref_metadata_2025_split huggingface dataset:
Characterization of Novel Human β-glucocerebrosidase Antibodies for Parkinson’s Disease Research
Authors: Jong Tiffany , Gehrlein Alexandra , Sidransky Ellen , Jagasia Ravi , Chen Yu 
Published: January 2024

Background: Mutations in GBA1, which encodes the lysosome enzyme β-glucocerebrosidase (also referred to as acid β-glucosidase or GCase), are the most common genetic risk factor for Parkinson’s disease (PD) and dementia with Lewy bodies (DLB). Evidence also suggests that loss of GCase activity is implicated in PD without GBA1 mutations. Consequently, therapies targeting GCase are actively being pursued as potential strategies to modify the progression of PD and related synucleinopathies. Despite this significant interest in GCase as a therapeutic target, the lack of well-characterized GCase antibodies continues to impede progress in the development of GCase-targeted therapies. Objective: This study aims to independently evaluate human GCase (hGCase) antibodies to provide recommendations for western blot, immunofluorescence, immunoprecipitation, and AlphaLISA (Amplified Luminescent Proximity Homogeneous Assay) assays. Methods: Two mouse monoclonal antibodies, hGCase-1/17 and hGCase-1/23, were raised against hGCase using imiglucerase, the recombinant enzyme developed to treat patients, as the antigen. These novel antibodies, alongside commonly used antibodies in the field, underwent evaluation in a variety of assays. Results: The characterization of hGCase-1/17 and hGCase-1/23 using genetic models including GBA1 loss-of-function human neuroglioma H4 line and neurons differentiated from human embryonic stem cells revealed their remarkable specificity and potency in immunofluorescence and immunoprecipitation assays. Furthermore, a hGCase AlphaLISA assay with excellent sensitivity, a broad dynamic range, and suitability for high throughput applications was developed using hGCase-1/17 and hGCase-1/23, which enabled a sandwich assay configuration. Conclusions: The hGCase immunofluorescence, immunoprecipitation, and AlphaLISA assays utilizing hGCase-1/17 and hGCase-1/23 will not only facilitate improved investigations of hGCase biology, but can also serve as tools to assess the distribution and effectiveness of GCase-targeted therapies for PD and related synucleinopathies.
Analisis dan Tindak Lanjut Hasil Asesmen Diagnostik Kognitif Mata Pelajaran Ilmu Pengetahuan Alam dan Sosial Sekolah Dasar
Authors: Forniawan Ary , Wati Dwi Retno 
Published: January 2024

Proses pembelajaran yang mengabaikan perbedaan pengetahuan awal peserta didik tidak membuat peserta didik merdeka dalam belajar. Guru harus memahami kelebihan dan kelemahan setiap peserta didik untuk menentukan tindak lanjut yang tepat. Penelitian ini bertujuan untuk menganalisis hasil dan tindak lanjut dari hasil asesmen serta menganalisis efektivitas pemberian asesmen diagnostik kognitif pada peningkatan pengetahuan peserta didik kelas IV SD Islam Daarul Hasanah pada mata pelajaran ilmu pengetahuan alam dan sosial materi tumbuhan. Metode penelitian kualititatif dengan pendekatan penelitian deskriptif. Subjek Penelitian guru mata pelajaran ilmu pengetahuan alam dan sosial serta peserta didik. Objek penelitian asesmen diagnostik kognitif. Teknik pengumpulan data dilakukan dengan wawancara, observasi dan dokumentasi. Hasil penelitian menunjukkan asesmen diagnostik kognitif yang dilakukan memiliki validitas dan reliabilitas yang tinggi. Namun, tingkat kesukaran 60% soal masih dikategorikan mudah dan daya beda soal masih rendah. Tindak lanjut hasil asesmen digunakan guru untuk merancang pembelajaran yang disesuaikan dengan tingkat pemahaman setiap individu peserta didik. Guru memberikan pengayaan pada peserta didik dengan pemahaman awal di atas rata-rata kelas dan pendampingan pada peserta didik dengan pemahaman awal di bawah rata-rata kelas. Asesmen diagnostik kognitif efektif meningkatkan pengetahuan peserta didik sebesar 12%.
Asociación entre alimentación y parasitosis intestinales en una comunidad rural de Ecuador: Un análisis epidemiológico
Authors: Robalino Flores Ximena del Rocío , Mora Gaibor Daniela Elizabeth , Luzón Ríos Dayanna Thalía , González Ramírez Luisa Carolina 
Published: January 2024

Introducción. Las infecciones enteroparasitarias representan un problema de la salud pública, por su elevada prevalencia en países en desarrollo. La población rural está expuesta al contagio debido a la pobreza, falta de agua potable y precarias condiciones higiénico-sanitarias. Objetivo. El propósito de esta investigación fue evaluar la asociación entre los alimentos ingeridos y los enteroparásitos diagnosticados en residentes de la comunidad de Cuatro Esquinas, San Andrés, Guano, Chimborazo. Metodología. Estudio descriptivo, de campo, transversal y prospectivo. El muestreo fue no probabilístico en bola de nieve. La información fue recopilada mediante encuestas y diagnóstico coproparasitológico (examen directo, Ritchie, Kato-Katz, Ziehl-Neelsen). Se evaluó a un total de 49 individuos (4 y 88 años), de sexo masculino (19) y femenino (30), quienes entregaron muestras fecales. Resultados. Todos los individuos estaban infectados, hubo mayor prevalencia de protozoos (100%) que de helmintos (4,08%) (X2=82,653; p<0,0001). Los parásitos predominantes fueron Blastocystis sp. (77,55%), Endolimax nana (67,35%) y Entamoeba coli (36,73%) (X2=170,85; p<0,0001), y el único helminto detectado fue Ascaris lumbricoides (4,08%). El estudio estadístico no comprobó asociación significancia entre los alimentos de consumo declarados (verduras, frutas, alimentos de origen animal, granos) y los parásitos detectados en las personas. Sin embargo, el estudio epidemiológico destaca que 83,67% de los individuos permanecen con las manos sucias (X2=22,837; p<0,0001) y que el 69,3% de los individuos consumen alimentos en puestos ambulantes (X2=53,327; p<0,0001). Conclusión. Se concluye que los alimentos de consumo declarados por los participantes no son vehículos de enteroparásitos, pero debe considerarse como factores asociados a la transmisión que la mayor parte de las personas permanecen con las manos sucias y consumen alimentos en puestos ambulantes. Área de estudio general: Laboratorio Clínico. Área de estudio específica: Parasitología. Tipo de estudio: Artículos originales.
Is there a relationship between Diffusion Weighted Imaging and Histopathological Type in Brain Metastases Due to Breast Cancer?
Authors: KAVAK Şeyhmus , ÇİLEDAĞ Nazan 
Published: January 2024

Aim: The aim of this study is to evaluate the relationship between diffusion-weighted imaging (DWI) properties and apparent diffusion coefficient (ADC) values of metastases with the histological type of breast cancer in patients with breast cancer-related brain metastasis.
Material and Methods: Between May 2008 - April 2011, 57 female patients who had been previously diagnosed with breast cancer in the radiology clinic were included in the study. Cases with invasive ductal carcinoma were considered group 1 (46 patients, 89 lesions) and cases with invasive lobular, comedo carcinoma and papillary cribriform carcinoma were considered group 2 ( 11 patients, 25 lesions). ADC values in both groups were compared by statistical analysis methods.
Results: In group 1; 37 lesions (41.57%) and in group 2; 13 lesions (52%) included cystic component. In the group of invasive ductal carcinoma 48 lesions (53.92%) and 18 lesions (72%) of second group included peritumoral edema. The mean ADC value of the solid component of metastases (group1: 1.105x10-3mm2/ s, group2: 1.099x10-3mm2/ s) was higher than the average ADC value of normal brain parenchyma (group1: 0.790x10-3mm2/s, group2: 0.801x10-3mm2/s), and was statistically significant (p
Epigenome-wide DNA methylation analysis of late-stage mild cognitive impairment
Authors: Zhang Yi , Shen Shasha 
Published: January 2024

Background: Patients with late-stage mild cognitive impairment (LMCI) have a higher risk of progression to Alzheimer’s disease (AD) than those with early-stage mild cognitive impairment (EMCI). However, previous studies have often pooled EMCI and LMCI patients into a single MCI group, with limited independent investigation into the pathogenesis of LMCI.Methods: In this study, we employed whole-genome methylation association analysis to determine the differences in peripheral blood methylation profiles between 663 cognitive aging (CN) and 554 LMCI patients.Results: Our results revealed 2,333 differentially methylated probes (DMPs) and 85 differentially methylated regions (DMRs) specific to LMCI. The top hit methylation sites or regions were associated with genes such as SNED1, histone deacetylases coding gene HDACs, and HOX and ZNF gene family. The DNA methylations upregulated the expression of HDAC4, HDAC8, and HOX family genes HOXC5 and HOXC9, but they downregulated the expression of SNED1, ADCYAP1, and ZNF family genes ZNF415 and ZNF502. Gene Ontology (GO) and KEGG analysis showed that the genes associated with these methylation sites were predominantly related to the processes of addiction disorders, neurotransmission, and neurogenesis. Out of the 554 LMCI patients included in this study, 358 subjects (65%) had progressed to AD. Further association analysis between the LMCI subjects with a stable course (sLMCI) and those who progressed to AD (pLMCI) indicated that the methylation signal intensities of HDAC6, ZNF502, HOXC5, HOXC6, and HOXD8 were associated with increased susceptibility to AD. Protective effects against progression to AD were noticed when the methylation of SNED1 and ZNF727 appeared in LMCI patients.Conclusion: Our findings highlight a substantial number of LMCI-specific methylated biomarkers that differ from those identified in previous MCI case–control studies. These biomarkers have the potential to contribute to a better understanding of the pathogenesis of LMCI.
Elucidating the binding mechanism of SARS-CoV-2 NSP6-TBK1 and structure-based designing of phytocompounds inhibitors for instigating the host immune response
Authors: Suleman Muhammad , Ishaq Iqra , Khan Haji , Ullah khan Safir , Masood Rehana , Albekairi Norah A. , Alshammari Abdulrahman , Crovella Sergio 
Published: January 2024

SARS-CoV-2, also referred to as severe acute respiratory syndrome coronavirus 2, is the virus responsible for causing COVID-19, an infectious disease that emerged in Wuhan, China, in December 2019. Among its crucial functions, NSP6 plays a vital role in evading the human immune system by directly interacting with a receptor called TANK-binding kinase (TBK1), leading to the suppression of IFNβ production. Consequently, in the present study we used the structural and biophysical approaches to analyze the effect of newly emerged mutations on the binding of NSP6 and TBK1. Among the identified mutations, four (F35G, L37F, L125F, and I162T) were found to significantly destabilize the structure of NSP6. Furthermore, the molecular docking analysis highlighted that the mutant NSP6 displayed its highest binding affinity with TBK1, exhibiting docking scores of −1436.2 for the wildtype and −1723.2, −1788.6, −1510.2, and −1551.7 for the F35G, L37F, L125F, and I162T mutants, respectively. This suggests the potential for an enhanced immune system evasion capability of NSP6. Particularly, the F35G mutation exhibited the strongest binding affinity, supported by a calculated binding free energy of −172.19 kcal/mol. To disrupt the binding between NSP6 and TBK1, we conducted virtual drug screening to develop a novel inhibitor derived from natural products. From this screening, we identified the top 5 hit compounds as the most promising candidates with a docking score of −6.59 kcal/mol, −6.52 kcal/mol, −6.32 kcal/mol, −6.22 kcal/mol, and −6.21 kcal/mol. The molecular dynamic simulation of top 3 hits further verified the dynamic stability of drugs-NSP6 complexes. In conclusion, this study provides valuable insight into the higher infectivity of the SARS-CoV-2 new variants and a strong rationale for the development of novel drugs against NSP6.
Resistance against two lytic phage variants attenuates virulence and antibiotic resistance in Pseudomonas aeruginosa
Authors: García-Cruz Juan Carlos , Rebollar-Juarez Xareni , Limones-Martinez Aldo , Santos-Lopez Cristian Sadalis , Toya Shotaro , Maeda Toshinari , Ceapă Corina Diana , Blasco Lucia , Tomás María , Díaz-Velásquez Clara Estela , Vaca-Paniagua Felipe , Díaz-Guerrero Miguel , Cazares Daniel , Cazares Adrián , Hernández-Durán Melisa , López-Jácome Luis Esaú , Franco-Cendejas Rafael , Husain Fohad Mabood , Khan Altaf , Arshad Mohammed , Morales-Espinosa Rosario , Fernández-Presas Ana María , Cadet Frederic , Wood Thomas K. , García-Contreras Rodolfo 
Published: January 2024

BackgroundBacteriophage therapy is becoming part of mainstream Western medicine since antibiotics of clinical use tend to fail. It involves applying lytic bacteriophages that self-replicate and induce cell lysis, thus killing their hosts. Nevertheless, bacterial killing promotes the selection of resistant clones which sometimes may exhibit a decrease in bacterial virulence or antibiotic resistance.MethodsIn this work, we studied the Pseudomonas aeruginosa lytic phage φDCL-PA6 and its variant φDCL-PA6α. Additionally, we characterized and evaluated the production of virulence factors and the virulence in a Galleria mellonella model of resistant mutants against each phage for PA14 and two clinical strains.ResultsPhage φDCL-PA6α differs from the original by only two amino acids: one in the baseplate wedge subunit and another in the tail fiber protein. According to genomic data and cross-resistance experiments, these changes may promote the change of the phage receptor from the O-antigen to the core lipopolysaccharide. Interestingly, the host range of the two phages differs as determined against the Pseudomonas aeruginosa reference strains PA14 and PAO1 and against nine multidrug-resistant isolates from ventilator associated pneumonia.ConclusionsWe show as well that phage resistance impacts virulence factor production. Specifically, phage resistance led to decreased biofilm formation, swarming, and type III secretion; therefore, the virulence towards Galleria mellonella was dramatically attenuated. Furthermore, antibiotic resistance decreased for one clinical strain. Our study highlights important potential advantages of phage therapy’s evolutionary impact that may be exploited to generate robust therapy schemes.
Safety and efficacy of NOAC vs. VKA in patients treated by PCI: a retrospective study of the FRANCE PCI registry
Authors: Durand Eric , Verrez Thibault , Gillibert Andre , Levesque Thomas , Barbe Thomas , Koning René , Motreff Pascal , Eltchaninoff Hélène , Collet Jean-Philippe , Rangé Gregoire 
Published: January 2024

IntroductionDual antithrombotic therapy (DAT) combining oral anticoagulation (OAC), preferentially Non-vitamin K antagonist OAC (NOAC) and single antiplatelet therapy (SAPT) for a period of 6–12 months is recommended after percutaneous coronary intervention (PCI) in patients with an indication for OAC.ObjectiveTo compare outcomes between vitamin K antagonist (VKA) and NOAC-treated patients in the nation-wide France PCI registry.MethodsAll consecutive patients from the France PCI registry treated by PCI and discharged with OAC between 2014 and 2020 were included and followed one-year. Major bleeding was defined as Bleeding Academic Research Consortium (BARC) classification ≥3 and major adverse cardiac events (MACE) as the composite of all-cause mortality, myocardial infarction (MI), and ischemic stroke. A propensity-score analysis was used.ResultsOf the 7,277 eligible participants, 2,432 (33.4%) were discharged on VKA and 4,845 (66.6%) on NOAC. After propensity-score adjustment, one-year major bleeding was less frequent in NOAC vs. VKA-treated participants [3.1% vs. 5.2%, −2.1% (−3.6% to −0.6%), p = 0.005 as well as the rate of MACE [9.2% vs. 11.9%, −2.7% (−5.0% to −0.4%), p = 0.02]. One-year mortality was also significantly decreased in NOAC vs. VKA-treated participants [7.4% vs. 9.9%, −2.6% (−4.7% to −0.5%), p = 0.02]. The area under ROC curves of the anticoagulant treatment propensity score was estimated at 0.93, suggesting potential indication biasConclusionsNOAC seems to have a better efficacy and safety profile than VKA. However, potential indication bias were found.
Comparison of EMG amplitudes recorded by ipsilateral and contralateral electrodes placement during using trans-thyroid cartilage recording method in thyroid surgery
Authors: Chiang Feng-Yu , Shih Yu-Chen , Lien Ching-Feng , Wang Chih-Chun , Wang Chien-Chung , Hwang Tzer-Zen , Huang Yaw-Chang , Wu Che-Wei , Yeh Tai-Hung , Huang Tzu-Yen 
Published: January 2024

ObjectivesThe feasibility and reliability of trans-thyroid cartilage EMG recording method (TCERM) during intraoperative monitoring (IONM) of the recurrent laryngeal nerve (RLN) in thyroid surgery have been established. This study compared two different recording electrode placements on the ipsi-lateral and contra-lateral lamina of the thyroid cartilage (TC).MethodsFifty consecutive patients undergoing total thyroidectomy with 100 RLNs at risk were enrolled. Two paired subdermal needle electrodes were inserted into the subperichondrium of the bilateral TC lamina to record electromyography (EMG) signals. The channel leads from the TC electrodes were connected to the patient interface with two different modes. In A-mode, the electrode leads were placed ipsi-laterally, and channel 1 monitored the left RLN and channel 2 monitored the right RLN respectively. In B-mode, the electrode leads were placed contra-laterally, and channels 1 and 2 simultaneously monitored the same side of the RLN. The amplitudes of four EMG signals (V1-R1-R2-V2) recorded by A-mode and B-mode were compared.ResultsAll EMG amplitudes of V1-R1-R2-V2 signals recorded with B-mode were all above 500μV and significantly higher than those with A-mode (p&lt;0.001). No false loss of signal, electrode dislodgement, or needle-related complications were noted during IONM. Postoperatively, all patients had symmetrical vocal cord movement. Lower EMG amplitudes were observed in older and male patients. Histopathology and laterality showed no significant differences in EMG amplitude.ConclusionDuring using TCERM in thyroid surgery, the recording electrodes should be placed contra-laterally on the TC lamina. This approach ensures high and stable EMG signals, which are important for high-quality IONM of the RLN.
Association between the weight-adjusted waist index and the odds of type 2 diabetes mellitus in United States adults: a cross-sectional study
Authors: Zheng Dongdong , Zhao Suzhen , Luo Dan , Lu Feng , Ruan Zhishen , Dong Xiaokang , Chen Wenjing 
Published: January 2024

ObjectiveTo examine the association between the weight-adjusted waist index (WWI) and the odds of type 2 diabetes mellitus(T2DM)among U.S. adults.MethodsData from the National Health and Nutrition Examination Survey (NHANES) spanning six years (2007–2018) were utilized, encompassing 31001 eligible participants. Weighted multivariate logistic regression models and smoothed fit curves were employed to assess the association between WWI and the odds of T2DM, as well as dose-response relationships in the overall population and the odds of T2DM in various subgroups.ResultsIn the fully adjusted continuous model, each one-unit increase in WWI was associated with a 1.14-fold increase in the odds of T2DM within the entire study population (2.14 [1.98,2.31], P &lt; 0.0001). In the fully adjusted categorical model, when using the lowest tertile of WWI (T1) as the reference group, the second tertile (T2) and the third tertile (T3) were associated with a 0.88-fold (1.88 [1.64,2.17], P &lt; 0.0001) and a 2.63-fold (3.63 [3.11,4.23], P &lt; 0.0001) increase in the odds of T2DM. These findings indicated a positive correlation between WWI values and the odds of T2DM, aligning with the results of the smoothed-fitted curves. In the analysis of subgroups, in addition to maintaining consistency with the overall population results, we found interactions between age and hypertension subgroups.ConclusionIn conclusion, WWI was found to be positively associated with the odds of T2DM in U.S. adults.
Impact of disease burden and late loss of B cell aplasia on the risk of relapse after CD19 chimeric antigen receptor T Cell (Tisagenlecleucel) infusion in pediatric and young adult patients with relapse/refractory acute lymphoblastic leukemia: role of B-cell monitoring
Authors: Molinos-Quintana Águeda , Alonso-Saladrigues Anna , Herrero Blanca , Caballero-Velázquez Teresa , Galán-Gómez Víctor , Panesso Melissa , Torrebadell Montserrat , Delgado-Serrano Javier , Pérez de Soto Concepción , Faura Anna , González-Martínez Berta , Castillo-Robleda Ana , Diaz-de-Heredia Cristina , Pérez-Martínez Antonio , Pérez-Hurtado José María , Rives Susana , Pérez-Simón José Antonio 
Published: January 2024

IntroductionLoss of B-cell aplasia (BCA) is a well-known marker of functional loss of CD19 CAR-T. Most relapses and loss of BCA occur in the first months after CD19 CAR-T infusion. In addition, high tumor burden (HTB) has shown to have a strong impact on relapse, especially in CD19-negative. However, little is known about the impact of late loss of BCA or the relationship between BCA and pre-infusion tumor burden in patients infused with tisagenlecleucel for relapsed/refractory B-cell acute lymphoblastic leukemia. Therefore, the optimal management of patients with loss of BCA is yet to be defined.MethodsWe conducted a Spanish, multicentre, retrospective study in patients infused with tisagenlecleucel after marketing authorization. A total of 73 consecutively treated patients were evaluated. ResultsPrior to infusion, 39 patients had HTB (≥ 5% bone marrow blasts) whereas 34 had a low tumor burden (LTB) (&lt;5% blasts). Complete remission was achieved in 90.4% of patients, of whom 59% relapsed. HTB was associated with inferior outcomes, with a 12-month EFS of 19.3% compared to 67.2% in patients with LTB (p&lt;0.001) with a median follow-up of 13.5 months (95% CI 12.4 – 16.2). In the HTB subgroup relapses were mainly CD19-negative (72%) whereas in the LTB subgroup they were mainly CD19-positive (71%) (p=0.017). In the LTB group, all CD19-positive relapses were preceded by loss of BCA whereas only 57% (4/7) of HTB patients experienced CD19-positive relapse. We found a positive correlation between loss of BCA and CD19-positive relapse (R-squared: 74) which persisted beyond six months post-infusion. We also explored B-cell recovery over time using two different definitions of loss of BCA and found a few discrepancies. Interestingly, transient immature B-cell recovery followed by BCA was observed in two pediatric patients. In conclusion, HTB has an unfavorable impact on EFS and allo-SCT might be considered in all patients with HTB, regardless of BCA. In patients with LTB, loss of BCA preceded all CD19-positive relapses. CD19-positive relapse was also frequent in patients who lost BCA beyond six months post-infusion. Therefore, these patients are still at significant risk for relapse and close MRD monitoring and/or therapeutic interventions should be considered.