bluuebunny/crossref_metadata_2025_split huggingface dataset:
Local Assessment of the Immunohistochemical Expression of Foxp3 + Regulatory T Lymphocytes in the Different Pathological Forms Associated with Bovine Paratuberculosis
Authors: Zapico David , Espinosa José , Fernández Miguel , Criado Miguel , Arteche-Villasol Noive , Pérez Valentín 
Published: December 2021

Abstract
Background

Mycobacterium avium subsp. paratuberculosis infected animals show a variety of granulomatous lesions: from focal forms, restricted to the gut-associated lymphoid tissue (GALT), related to latency and resistance, to diffuse lesions, with abundant (multibacillary) or scant (paucibacillary) bacteria, seen in clinical stages. Factors that determine the response to the infection and responsible for the occurrence of the different types of lesion are still not fully determined. It has been seen that regulatory T cells (Treg) play an important role in the progress of various diseases where they act on the limitation of the immunopathology associated with the immune response. In the case of paratuberculosis (PTB) the role of Treg lymphocytes in the immunity against Map is far away to be completely understood; therefore, several studies addressing this subject have appeared recently. The aim of this work was to assess, by immunohistochemical methods, the presence of Foxp3+ T lymphocytes in intestinal samples with different types of lesions seen in cows with PTB.
Methods

Intestinal samples of twenty cows showing the different pathological forms of PTB were evaluated: uninfected controls (n = 5), focal lesions (n = 5), diffuse paucibacillary (n = 5) and diffuse multibacillary (n = 5) forms. Foxp3+ lymphocyte distribution was assessed by differential cell count in intestinal lamina propria (LP), gut-associated lymphoid tissue (GALT) and mesenteric lymph node (MLN).
Results

A significant increase in the number of Foxp3+ T cells was observed in all infected animals, but this increase was only significant in cows with focal lesions and, to a lesser extent, in animals with diffuse paucibacillary forms. The former showed the highest numbers, significantly different from those found in cows with diffuse lesions, where no differences were noted between the two forms. No specific distribution pattern was observed within the granulomatous lesions in any of the groups.
Conclusions

The increase of Foxp3+ T cells in focal forms, that have been associated with latency or resistance to infection, suggest an anti-inflammatory action of these cells at these stages, helping to prevent exacerbation of the inflammatory response, as occurs in diffuse forms, responsible for the appearance of clinical signs.
Mass Transfer Behavior and Microstructure Evolution of Li4TiO4-Li2TiO3 Core-shell Breeding Ceramic Under Harsh Operating Conditions
Authors: Chen Ruichong , Katayama Kazunari , Qi Jianqi , Ipponsugi Akito , Oyama Ran , Guo Hao , Lu Tiecheng 
Published: December 2021

Abstract
The development of novel tritium breeding materials was urgently needed in order to continuously optimize the tritium breeding ratio (TBR) of thermonuclear fusion reactors. From this point of view, Li4TiO4-Li2TiO3 core-shell breeding materials with more reasonable structure and theoretical Li density of 0.464 g/cm3 were prepared in this work. Notably, the mass transfer experiment at 900 °C in 1% H2/Ar shows that the theoretical Li density of this core-shell material after heating for 30 days was significantly higher than that of other breeding materials, indicating that it can provide more stable and efficient TBR. Specifically, the Li mass loss of the sample after 30 days heating was 3.4%, resulting in a decrease of Li density to 0.415 g/cm3. The mechanism of Li mass loss in Li4TiO4-Li2TiO3 core-shell breeding materials was investigated in detail. Moreover, the samples did not crack or collapse during the long-term heating process, and always maintained a satisfactory crushing load, revealing that this core-shell breeding ceramic can be used for a long time under severe operating conditions.
Molecular Detection and Characterization of Porcine Astrovirus on the basis of Partial ORF1b/ORF2 Region
Authors: Kaur Rajpreet , KUMAR PARVEEN , Jindal Naresh , Minhas Sanjeevna Kumari , Prakash Anand , Dahiya Swati , Kakker Naresh , Joshi Vinay G. 
Published: December 2021

Abstract
The porcine astrovirus (PAstV) is distributed globally and exists as five distinct lineages (PAstV1-PAstV5). PAstV is considered one of the important pathogen associated with diarrhea among pigs. In the present study, the PAstV was detected in 13.4% (19/141) of fecal samples including 14.4% (16/111) diarrheic and 10% (3/30) non-diarrheic samples by RT-PCR based on partial ORF1b/ORF2 gene from Haryana, India. The results indicated that the weaning piglets were more susceptible to PAstV infection followed by suckling piglets. The phylogenetic analysis of the viral strains revealed the circulation ofPAstV4 (55.5%) and PAstV2 (44.4%) lineages with PAstV4 being the predominant lineage. To conclude, RT-PCR screening followed by sequencing of PAstV revealed high genetic diversity among the PAstV strains suggesting the wide range of heterogeneity and possible recombination events of viral strains in the state.
What’s the difference between hyperprogressive disease and progressive disease for patients with treated immune checkpoint inhibitors?
Authors: Yıldırım Hasan Çağrı , Guven Deniz Can , Aktepe Oktay Halit , Taban Hakan , Yilmaz Feride , Yasar Serkan , Aktaş Burak Yasin , Güner Gürkan , Dizdar Ömer , Aksoy Sercan , Erman Mustafa , Yalcin Suayib , Kilickap Saadettin 
Published: December 2021

Abstract
Background

Although the immune checkpoint inhibitors (ICIs) became a vital part of cancer care, many patients do not respond to treatment. Some of the patients in this group, which is considered to have hyperprogressive disease (HPD), have a shorter overall survival compared to progressive disease (PD). Therefore, biomarkers are needed to differentiate between HPD and PD. Here, we evaluated PILE score to differentiate HPD from PD in patients treated with ICI.
Methods

Ninety-five patients treated with anti-PD-1 or anti-PD-L1 inhibitors for any type of cancer with progression according to RECIST criteria in the first control imaging were included. HPD was defined according to Russo's work. The PILE scoring system was calculated, including PIV (< median vs. ≥ median), LDH (normal and > normal), and ECOG performance status (0 vs. ≥ 1). The relationship between PILE score and HPD was examined.
Results

The median follow-up was 6.6 months and the median OS of all cohort were 11.18 ± 1.36 months. The patients in the HPD group had decreased OS (4.77 ± 0.89 vs. 13.94 ± 1.80 months, p <0.001) and PFS (1.89 ± 0.11 vs. 3.16 ± 0.12 months, p <0.001) compared to PD group. The risk of HPD was higher than the risk of PD in patİents with a high PILE score (p:0.001).
Conclusion

In this study, we showed that patients treated with ICI with a higher PILE score are at greater risk for HPD. If prospective studies confirm our results, the PILE score may be a biomarker to differentiate HPD from PD.
A simple and accurate method to calculate square roots and cube roots for Chemistry students without calculator.
Authors: Iyengar Anju 
Published: December 2021

Abstract
Presented here are two simple formulae, for the calculation of square and cube roots that are frequently encountered in Chemistry courses, at school and college levels (whether undergraduate or graduate). However, tests are difficult to be designed which do not provide for a calculator and which require the calculation of these quantities. The formulae are simple interval-weighted denominator method based to get an accurate value of these quantities. This will enable students to quickly and accurately compute square roots and cube roots.
Preoperative Inflammatory Response to Esophageal Cancer Is More Reliable Prognostic Factor in Patients Received Esophagectomy
Authors: Fujiwara Yoshinori , Endo Shunji , Higashida Masaharu , Kubota Hisako , Kinoshita Seiya , Yoshimatsu Kazuhiko , Ueno Tomio 
Published: December 2021

Abstract
Background: Inflammation and nutrition are closely related to the progression of gastrointestinal malignancies. We aimed to explore the potential of preoperative inflammation-based or nutrition-based biomarkers as predictors of survival in patients with resectable esophageal squamous cell carcinoma (ESCC) using multivariate Cox analysis.Methods: We included 122 patients with resectable ESCC (stages I–IV) in the study. We assessed the inflammation-based modified Glasgow prognostic score (mGPS), nutrition-based modified controlling nutritional status (mCONUT) score, CRP(C-reactive protein),serum albumin, lymphocyte counts, and total cholesterol. The relationships of these biomarkers with overall survival (OS) and recurrence-free survival (RFS) were evaluated. Three Cox model were performed for single parameters(CRP, albumin, lymphocyte, total cholesterol), for mCONUT and mGPS,and for clinicopathological factors.Results: The cut-off values for CRP, albumin, and mCONUT measured using receiver operating characteristic (ROC) curves were 0.3, 3.5, and 4, respectively. Patients with high mGPS and high mCONUT scores were significantly associated with shorter OS and RFS (p < 0.05).Multivariate Cox analysis showed that mGPS,pStage,tumor location were independent prognostic factors both FRS and OS. Also, Cox analysis for single parameters showed that preoperative CRP, lymphocyte counts were independent prognostic factors for RFS and albumin was prognostic factor for OS.Conclusions: Preoperative inflammation-based mGPS is most reliable independent prognostic factor in patients with resectable ESCC. Suppression of preoperative inflammation can be improved nutritional status and may improve the prognosis in these patients.
Spatial Patterns and Climate Drivers of Malaria in Three Border Areas of Brazil, Venezuela and Guyana, 2016-2018
Authors: Wangdi Kinley , Wetzler Erica , Cox Horace , Marchesini Paola , Villegas Leopoldo , Canavati Sara 
Published: December 2021

Abstract
IntroductionIn 2020, 77% of malaria cases in the Americas were concentrated in Venezuela, Brazil, and Colombia. These countries are characterized by a heterogeneous malaria landscape and malaria hotspots. Furthermore, the political unrest in Venezuela has led to significant cross-border population movement. Hence, the aim of this study was to describe spatial patterns and identify significant climatic drivers of malaria transmission along the Venezuela-Brazil-Guyana border, focusing on Bolivar state, Venezuela and Roraima state, Brazil.MethodsMalaria case data, stratified by species from 2016-2018, were obtained from the Brazilian Malaria Epidemiology Surveillance Information System, the Guyana Vector Borne Diseases Program, the Venezuelan Ministry of Health, and civil society organizations. Spatial autocorrelation in malaria incidence was explored using Getis-Ord (Gi*) statistics. A Poisson regression model was developed with a conditional autoregressive prior structure and posterior parameters were estimated using the Bayesian Markov chain Monte Carlo simulation with Gibbs sampling. Climatic covariates were precipitation and minimum and maximum temperature. ResultsThere were 685,498 malaria cases during the study period. Plasmodium vivax was the predominant species (71.7%, 490,861). Malaria hotspots were located in eight municipalities along the Venezuela and Guyana international borders with Brazil. Plasmodium falciparum decreased by 1.6% (95% credible interval [CrI] 1.5%, 2.3%) and 9.6% (95% CrI 1.5%, 25.2%) per 1 cm increase in six-month lagged precipitation and each 1°C increase of minimum temperature without lag. Each 1°C increase of one-month lagged maximum temperature increased P. falciparum by 6.6% (95% CrI 4.8%, 21.7%). P. vivax cases decreased by 1.0% (95% CrI 1.0%, 1.1%) and 7.0% (95% CrI 6.5%, 7.5%) for each 1 cm increase of precipitation lagged at six-months and 1°C increase in minimum temperature lagged at six-months. There was no significant residual spatial clustering after accounting for climatic covariates.ConclusionMalaria hotspots were located along the Venezuela and Guyana international border with Roraima state, Brazil. In addition to population movement, climatic variables are important drivers of malaria transmission in these areas.
Paris Polyphylla Monomer PP-26 Induces Mitochondrial Pathway-Mediated Cell Apoptosis by Inhibiting the PI3K/Akt Pathway in Human Gastric Cancer Cells
Authors: Chen Jiajin , Zhou Junzhen , Xu Jun , Zhao Na , Li Qiang , Zhang Xiaoying , Liu Zhilong , Zhang Qing , Wang Guocai , Wang Yuechun , Jiang Jianwei 
Published: December 2021

Abstract
Background: Paris polyphylla is a traditional Chinese medicinal herb that has been used as a haemostatic, antimicrobial and anticancer agent. Gastric cancer (GC) is a global health problem, with more than 1 million people newly diagnosed with gastric cancer worldwide each year.Methods: The MTT and colony formation assay were used to test the anti-proliferative effects of PP-26 on MGC-803 and BGC-823 cells. Flow cytometry assays, Hoechst 33258 staining assay and Caspase inhibitor Z-VAD-FMK were used to test apoptosis. JC-1 staining used to measure changes in mitochondrial membrane potential and western blot analysis were used to test apoptotic and PI3K/Akt pathway related proteins.Results: PP-26 had a dose-dependent inhibitory effect on the proliferation of MGC-803 and BGC-823 cells, but had no obvious anti-proliferative effect on normal liver LO2 cells and normal embryonic kidney HEK-293 cells. Additionally, PP-26 induced typical apoptotic morphological changes, such as nuclear pyknosis, nuclear cracking and apoptotic bodies. Moreover, PP-26 induced a decrease in mitochondrial membrane potential. And PP-26 modulated the expression of Bcl-xL, Mcl-1, Bax, caspase-9/-3 and PARP proteins and induced cell apoptosis through the mitochondrial apoptotic pathway. Next, using an irreversible general caspase inhibitor (Z-VAD-FMK), we confirmed the activation of the mitochondrial apoptotic pathway induced by PP-26. Furthermore, PP-26 inhibited the phosphorylation of Akt and GSK-3β. The inhibition of Akt protein activated the mitochondrial apoptotic pathway.Conclusion: Collectively, these results indicated that PP-26 inhibited the proliferation of MGC-803 and BGC-823 cells by inhibiting the Akt signalling pathway and activating the mitochondrial apoptotic pathway.
Sesquiterpene from Polygonum Barbatum Disrupt Mitochondrial Membrane Potential to Induce Apoptosis and Inhibits Metastasis by Downregulating Matrix Metalloproteinase and Osteopontin in NCI-H460 Cells
Authors: Zehra Binte , Ahmed Ayaz , Khan Ajmal , Shams Afshan , Uddin Reaz , Rafi Sidra , Khan Taseer Ahmed , Farooq Umar , Ali Syed Abid 
Published: December 2021

Abstract
Background: Globally, lung cancer accounts for 18% of cancer-associated mortalities. Among the subtypes, non-small-cell lung cancer (NSCLC) is the most prevalent one. The increased resistance and poor survival rates, signifies disease aggressiveness and thus require a search for an alternative anticancer molecule. Hypothesis/Purpose: Earlier, the isolated sesquiterpene i.e. compound 1 ((E)-Methyl 6-acetoxy-7-methoxy-1-(2-methylpropylidene)-1H-indene-3-carboxylate) from P. barbatum was isolated, characterized by us and reported for preliminary anticancer activity. Considering its potent activity, this study was designed to explore the underlying molecular mechanism of apoptosis and metastasis against NCI-H460 cells. Method: The molecular mechanism of compound 1 inducing apoptosis and inhibiting metastasis was elucidated by analyzing mitochondrial membrane potential, DNA fragmentation, clonogenic assay, invasion assay and expression of apoptotic (Caspases 3, 6, 8, 9 and BAK) and metastatic markers (MMP 2, 9 and osteopontin). Results: Compound 1 significantly inhibited cell proliferation and induced apoptosis via intrinsic route i.e. the mitochondrial pathway by disrupting mitochondrial membrane potential. The enhanced expression of caspases 6, 9, BAK and HRK with downregulation of Bcl-2L1 and Ki67 further confirmed the involvement of the intrinsic apoptotic pathway. Moreover, compound 1 restricted the invasive nature of NCI-H460 cells evinced by reduced cell invasion in Boyden chamber invasion assay and downregulating the expression of metastatic markers i.e. matrix metalloproteinase 2 / 9 and VEGF. It was also found that it blocks osteopontin by negatively regulating its expression; a marker protein in cancer management. Conclusion: Conclusively, this sesquiterpene exhibited potent anticancer and anti-metastatic activity and can be explored further as possible pharmacophores
Evaluating Student Levelling Based on Machine Learning Model’s Performance
Authors: Ghareeb Shatha , Hussain Abir Jaafar , Al-Jumeily Dhiya , Khan Wasiq , Al-Jumeily Rawaa , Baker Thar , shammaa Ahmed Al , Khalaf Mohammed 
Published: December 2021

Abstract
In this paper, a novel application of machine learning algorithms is presented for student levelling. In multicultural countries such as UAE, there are various education curriculums where the sector of private schools and quality assurance is supervising various private schools for many nationalities. As there are various education curriculums in United Arab Emirates, specifically Abu Dhabi, to meet expats’ needs, there are different requirements for registration and success. In addition, there are different age groups for starting education in each curriculum. Every curriculum follows different education methods such as assessment techniques, reassessment rules, and exam boards. Currently, students who transfer to other curriculums are not correctly placed to their appropriate year group as a result of the start and end dates of each academic year as well as due to their date of birth, in which students who are either younger or older for that year group can create gaps in their learning and performance. In addition, pupils’ academic journeys are not stored which create a gap for the schools to track their learning process. In this paper, we propose a computational framework applicable in multicultural countries such as United Arab Emirates in which multi-education systems are implemented. Machine Learning are used to provide the appropriate student’ level aiding shoolds to provide a smooth transition when assigning students to their year groups and provide levelling and differentiation information of pupils for a smooth transition between one education curriculums to another, in which retrieval of their progress is possible. For classification and discriminant analysis of pupils levelling, three machine learning classifiers are utilised including random forest classifier, Artificial Neural Network, and combined classifiers. The simulation results indicated that the proposed machine learning classifiers generated effective performance in terms of accuracy.
Dynamics of Parasympathetic Activity in Violent Incarcerated Offenders Before, During, and in Recovery From An Emotional Inhibition Task
Authors: Palix Julie , Gillespie Steven M. , Abbiati Milena , Abu-Akel Ahmad 
Published: December 2021

Abstract
Dynamics of the autonomic nervous system (ANS) are hypothesized to play a role in the emergence of interpersonal violence. In the present study, we examined continuous activities of the inhibitory parasympathetic pathway of the ANS through the root mean square of successive differences between normal heartbeats (RMSSD) in 22 male offenders who committed interpersonal violence and 24 matched controls from the general population across three successive phases: resting baseline, while performing an emotional Go/No-Go task, and post-task recovery. Results showed that across the three phases, the offender group presented lower RMSSD at baseline (pFDR = .003; Cohen’s d = -1.11), but similar levels during the task, attributed to a significant increase in their RMSSD level (pFDR = .027, Cohen’s d = -1.26). During recovery, no distinction between the two groups was found, but although both groups showed signs of recovering toward baseline values. These findings suggest that violent incarcerated offenders can flexibly engage parasympathetic resources to meet environmental challenges. This underscores the necessity of considering parasympathetic dynamics and its respective mobilization/flexibility to better understand ANS profiles underlying interpersonal violence and designed more tailored intervention.
Banoxantrone Coordinated Metal-Organic Framework for Photoacoustic Imaging-Guided High Intensity Focused Ultrasound Therapy
Authors: Sun Tingyu , Li Jingnan , Zeng Chao , Luo Chengyan , Luo Xirui , Zhang Huijie , Li Huanan 
Published: December 2021

Abstract
Background
Photoacoustic imaging (PA) with high spatial resolution has great potential as desired monitoring means in the high intensity focused ultrasound (HIFU) surgery of tumor. However, its penetration depth in the tissue does not meet the clinical needs. Nanomedicine provides a new opportunity for PA imaging to guide HIFU surgery. Our studies found that hypoxic heterogeneity of tumor was effectively reversed by HIFU.
Methods
Herein, specific metal-organic framework nanosystem, constructed by coordination of banoxantrone (AQ4N) and Mn2+, is designed based on HIFU to reverse hypoxic heterogeneity of tumor.
Results
It could provide exogenous light-absorbing substances, thus improves the penetrability of PA imaging signal through the deep tissue and achieves clearer PA imaging for guiding HIFU surgery. In turn, AQ4N, in the hypoxic homogenous environment of tumor provided by HIFU, is activated sequentially to specifically treat the residual hypoxic tumor cells.
Conclusions
This strategy addresses the dissatisfaction of PA imaging-guided HIFU therapy and is promising for translation into a clinical combination regimen.
Role of SPAK-NKCC1 Signaling Cascade in the Choroid Plexus Blood-CSF Barrier Damage After Stroke
Authors: Wang Jun , Liu Ruijia , Hasan Md Nabiul , Fischer Sydney , Como Matt , Fiesler Victoria M , Begum Gulnaz , Chen Yang , Bhuiyan Mohammad Iqbal H. , Dong Shuying , Li Eric , Kahle Kristopher T , Zhang Jinwei , Deng Xianming , Subramanya Arohan R , Yin Yan , Sun Dandan 
Published: December 2021

Abstract
Background: The mechanisms underlying dysfunction of choroid plexus (ChP) blood-cerebrospinal fluid (CSF) barrier and lymphocyte invasion in neuroinflammatory responses to stroke are not well understood. In this study, we investigated whether stroke damaged the blood-CSF barrier integrity due to dysregulation of major ChP ion transport system Na+-K+-Cl- cotransporter (NKCC1) and regulatory Ste20-related proline-alanine-rich kinase (SPAK).
Methods: Sham or ischemic stroke was induced in C57Bl/6J mice. Changes of the SPAK-NKCC1 complex and tight junction proteins (TJs) in the ChP were quantified by immunofluorescence staining and immunoblotting. Immune cell infiltration in the ChP was assessed by flow cytometry and immunostaining. Cultured ChP epithelium cells (CPECs) and cortical neurons were used to evaluate H2O2-mediated oxidative stress in stimulating the SPAK-NKCC1 complex and cellular damage. In vivo or in vitro pharmacological blockade of the ChP SPAK-NKCC1 cascade with SPAK inhibitor ZT-1a or NKCC1 inhibitor bumetanide were examined.
Results: Ischemic stroke stimulated activation of the CPECs apical membrane SPAK-NKCC1 complex, NF-κB, and MMP9, which was associated with loss of the blood-CSF barrier integrity and increased immune cell infiltration into the ChP. Oxidative stress directly activated SPAK-NKCC1 pathway and resulted in apoptosis, neurodegeneration, and NKCC1-mediated ion influx. Pharmacological blockade of the SPAK-NKCC1 pathway protected the ChP barrier integrity, attenuated ChP immune cell infiltration or neuronal death.
Conclusion: Stroke-induced pathological stimulation of the SPAK-NKCC1 cascade caused CPECs damage and disruption of TJs at the blood-CSF barrier. The ChP SPAK-NKCC1 complex emerged as a therapeutic target for attenuating ChP dysfunction and lymphocyte invasion after stroke.