bluuebunny/crossref_metadata_2025_split huggingface dataset:
BCG vaccination induces different mechanisms of mycobacterial growth control compared to natural protection
Authors: Meijgaarden Krista van , Li Wenchao , Moorlag Simone , Koeken Valerie , Koenen Hans , Joosten Leo , Vyakarnam Annapurna , Ahmed Asma , Rakshit Srabanti , Adiga Vasista , Ottenhoff Tom , Li Yang , Netea Mihai , Joosten Simone 
Published: December 2022

Abstract
Bacillus Calmette-Guèrin (BCG) vaccination induces considerable protection in infants and young children against not only severe forms of tuberculosis (TB), but also all-cause mortality and heterologous infections. These effects are mediated through a combination of specific adaptive immune memory and sustained innate immune activation (also called trained immunity). To delineate factors influencing mycobacterial growth control, we investigated the effects of BCG vaccination in healthy Dutch adults. About a quarter of individuals already controlled BCG outgrowth prior to vaccination, whereas a quarter of vaccinees acquired the capacity to control 3 months upon BCG vaccination. This leaves a considerable percentage of the population (54% of total) incapable to control BCG outgrowth even after vaccination. Detailed characterization of biological samples, including single cell RNA sequencing (scRNAseq), identified multiple processes associated with mycobacterial growth control. Differential gene expression was abundant in all cell types of individuals with natural control, compared to those who did not control mycobacterial growth. In contrast, BCG-induced acquired control was mostly characterized by differential gene expression in monocytes. Control prior to BCG vaccination was associated with increased oxidative phosphorylation, whereas control acquired upon BCG vaccination was associated with glycolysis. Moreover, samples with natural control expressed genes linked to the type I IFN pathway, whereas samples with acquired control expressed genes associated with the Th1 pathway. These data suggest that natural control and control induced upon BCG vaccination employ different mechanisms to control BCG outgrowth, and that a substantial proportion of individuals (≈50%) fail to develop measurable growth control even following BCG vaccination.
Genetic diversity analysis of volunteer wheat based on microsatellite simple sequence repeats(SSR) markers
Authors: Su Wangcang , Xu Hongle , Sun Lanlan , Wu Renhai , Lu Chuantao 
Published: December 2022

Abstract
In order to study the genetic diversity and population structure within and between volunteer wheat and cultivated wheat(Triticum aestivum L.), 195 volunteer wheats and 29 cultivated wheats were analyzed based on 16 pairs of highly-polymorphic microsatellite simple sequence repeats (SSR) primers and a microchip capillary electrophoresis (MCE) detection system. A total of 110 polymorphic alleles were detected by capillary electrophoresis(CE) with each pair of primers identifying 2–15 alleles with an average of 6.875 alleles. The polymorphic information content (PIC) ranged from 0.1089 to 0.7843, with an average of 0.5613. Genetic diversity arguments from 224 samples showed that volunteer wheat was more varied than cultivated wheat. Based on the SSR information, the 224 samples were classified into seven groups, which corresponded to the volunteer wheats and cultivated wheats through principle component analysis (PCA). We propose that volunteer wheat and cultivated wheat have rather distant phylogenetic relationships. Hence, it is important for wheat breeding to study the genetic relationship between volunteer wheat and cultivated wheat.
Identification of novel protein biomarkers and drug targets for colorectal cancer by integrating human plasma proteome with genome
Authors: Sun Jing , Zhao Jianhui , Jiang Fangyuan , Wang Lijuan , Xiao Qian , Han Fengyan , Chen Jie , Yuan Shuai , Wei Jingsun , Larsson Susanna , Honghe Zhang , Dunlop Malcolm , Farrington Susan , Ding Kefeng , Theodoratou Evropi , Li Xue 
Published: December 2022

Abstract
Background:Proteome is a major source of therapeutic targets. We conducted a proteome-wide Mendelian randomization (MR) study to identify candidate protein markers and therapeutic targets for colorectal cancer (CRC).
Methods: Protein quantitative trait loci (pQTL) were derived from seven published genome-wide association studies (GWAS) on plasma proteosome, and summary-level data were extracted for 4,853 circulating protein markers. Genetic associations with CRC were obtained from a large-scaled GWAS meta-analysis (16,871 cases and 26,328 controls), the FinnGen cohort (4,957 cases and 304,197 controls) and the UK Biobank (9,276 cases and 477,069 controls). Colocalization and summary-data-based MR (SMR) analyses were performed sequentially to verify the causal role of candidate proteins. Single cell-type expression analysis, protein-protein interaction (PPI), and druggability evaluation were further conducted to detect the specific cell type with enrichment expression and prioritize potential therapeutic targets.
Results: Collectively, genetically predicted levels of 13 proteins were associated with CRC risk. Elevated levels of two proteins (GREM1, CHRDL2) and decreased levels of 11 proteins were associated with an increased risk of CRC, among which six (CLSTN3, POLR2F, ADPGK, CSAG1, STXBP6, FUT3) were novel protein markers. These protein-coding genes mainly expressed in tissue stem cells, epithelial cells, and monocytes in colon tumor tissue. Two interactive pairs of proteins (GREM1 and CHRDL2; MMP2 and TIMP2) were identified to be involved in osteoclast differentiation and tumorigenesis pathways; four proteins (POLR2F, CSF2RA, CD86, MMP2) have been targeted for drug development on autoimmune diseases and other cancers, with the potentials of being repurposed as therapeutic targets for CRC.
Conclusion: This study identified several protein biomarkers to be associated with CRC risk and provided new insights into the etiology and promising targets for the development of screening biomarkers and therapeutic drugs for CRC.
Warburg effect enhanced by AKR1B10 promotes acquired resistance to pemetrexed in lung cancer-derived brain metastasis
Authors: Liu Wenwen , Duan Wenzhe , Xia Shengkai , Zhou Yang , Tang Mengyi , Xu Mingxin , Li Xinyu , Wang Qi 
Published: December 2022

AbstractBackground Pemetrexed (PEM), as a rare chemotherapeutic agent that can efficiently cross the blood-brain barrier, has profound implications for the treatment of patients with lung cancer brain metastasis (BM). However, resistance to PEM limits the therapeutic efficacy. Aldo-keto reductase family 1 B10 (AKR1B10) was recently found to be elevated in lung cancer BM. The link between AKR1B10 and BM-acquired PEM is unknown. Methods PEM drug-sensitivity was assessed in the preclinical BM model of PC9 lung adenocarcinoma cells and the BM cells with or without AKR1B10 interferencein vitroandin vivo.Metabolic reprogramming of BM attributed to AKR1B10 was identified by chromatography-mass spectrometry (GC-MS) metabolomics, and the mechanism of how AKR1B10 mediates PEM chemoresistance via a way of modified metabolism was revealed by RNA sequencing as well as further molecular biology experimental approaches. Results The brain metastasis subpopulation (PC9-BrM3) showed obvious resistance to PEM compared to the parental PC9 cells and silencing AKR1B10 in BM cells could increase the PEM sensitivityin vitroandin vivo. Metabolic profiling revealed that AKR1B10 prominently facilitated the Warburg metabolism characterized by the overproduction of pyruvate and lactate. Glycolysis regulated by AKR1B10 is vital for the resistance of lung cancer BM cells to PEM. In mechanism, knockdown of AKR1B10 elicited inhibition of a series of glycolysis-related enzymes (LDHA, LDHB) at the transcriptional level. Besides, the Warburg effects enhanced by AKR1B10 constantly fueled phosphoinositide 3-kinase signaling, which was also helpful for the chemoresistance. Conclusions Our finding demonstrated that AKR1B10 promotes acquired PEM resistance in lung cancer BM, providing novel strategies to sensitize PEM response in the treatment of lung cancer patients suffering from BM.
Lysophosphatidylethanolamine correlated with cognitive improvements after treatment with olanzapine in drug-naïve first-episode schizophrenia: a prospective cohort study
Authors: Su Lei , Xiu Meihong , Guan Xiaoni , Wu Fengchun 
Published: December 2022

Abstract
Background
Cognitive deficits are a core symptom of schizophrenia (SCZ). Lysophosphatidylethanolamine (LysoPE) has been reported to be involved in cognitive decline, but no studies have investigated its role in cognitive impairment in SCZ. The aim of this study was to evaluate whether plasma LysoPE could predict the cognitive effects of olanzapine (OLA) monotherapy in SCZ.
Methods
Twenty-five drug-naïve first-episode (DNFE) patients with SCZ were recruited and treated with OLA for 4 weeks. Cognitive function was evaluated at baseline and at 4-week follow-up. LysoPE concentrations were measured by an untargeted ultra-performance liquid chromatography mass spectrometry (UPLC-MS)-based metabolomics approach.
Results
Significant improvements in immediate memory and delayed memory domains were observed after treatment. Nine differential LysoPE species were identified after OLA monotherapy, and all LysoPE concentrations were significantly increased after treatment, except for LysoPE(22:6). Increased LysoPE(22:1) concentration was positively correlated with cognitive improvement in patients. Baseline LysoPE(16:1) was a predictor for cognitive improvement after OLA monotherapy. Further regression analyses, after controlling for confounders, confirmed all these associations found in this study.
Conclusion
Our study provides preliminary evidence for the role of LysoPE in cognitive improvement after OLA treatment in patients with first-episode drug-naïve SCZ.
The Influence of Fixation and Cryopreservation of Cerebrospinal Fluid on Antigen Expression and Cell Percentages by Flow Cytometric Analysis
Authors: Singh Gabriela , Laarhoven Arjan , Adams Rozanne , Reid Timothy Dawson , Combrinck Jill , Dorp Suzanne , Riou Catherine , Thango Nqobile , Enslin Johannes , Kruger Stefan , Figaji Anthony Aaron , Rohlwink Ursula Karin 
Published: December 2022

Abstract
The pauci-cellular nature of cerebrospinal (CSF), particularly ventricular CSF, and the rapid cell death following sampling, incumbers the use of flow cytometric analysis of these samples in the investigation of central nervous system (CNS) pathologies. Developing a method that allows long-term storage and batched analysis of CSF samples without compromising cell integrity is highly desirable in clinical research, given that CSF is often sampled after hours creating logistical difficulties for fresh processing. We examined percentages and relative proportion of peripheral and brain-derived immune cells in Cryopreserved and Transfix-treated CSF, compared to freshly processed CSF. Cell proportions were more comparable between Fresh and Cryopreserved CSF (mean of differences = 3.19), than between Fresh and Transfix-treated CSF (mean of differences = 14.82). No significant differences in cell percentages were observed in Fresh versus Cryopreserved CSF; however significantly lower cell percentages were observed in Transfix-treated CSF compared to Fresh CSF [(CD11b++ (p = 0.01), CD4+ (p = 0.001), CD8+ (p = 0.007), NK cells (p = 0.04), as well as CD69+ activation marker (p = 0.001)]. Furthermore, loss of marker expression of various lymphocyte sub-populations were observed in Transfix-treated CSF. Cryopreservation is a feasible option for long-term storage of ventricular CSF and allows accurate immunophenotyping of peripheral and brain-derived cell populations by flow cytometry.
Molecular evidence of the intestinal exposure to Ancylostoma caninum among humans in Jamaica
Authors: Lee Mellesia F. , Cadogan Paul , Eytle Sarah , Walochnik Julia , Lindo John 
Published: December 2022

Abstract
Canine and feline hookworms are important causes of skin infections in humans including creeping eruption or cutaneous larva migrans. Further, Ancylostoma caninum has been shown to cause intestinal infections in humans resulting in eosinophilic enteritis. To determine the prevalence of Ancylostoma species in dogs and possible intestinal exposure of humans in Jamaica, stool samples from both species were screened using PCR targeting the internal transcribed spacer (ITS-1), 5,8S and ITS-2 region of the ribosomal DNA genes. The prevalence of hookworm infections in dogs based on PCR was 60.9% (78/128). DNA sequencing revealed that A. caninum accounted for 88.2% (30/34) and A. braziliense for 11.8% (4/34) of infections in dogs. Further, DNA of A. caninum targeting the same gene fragment was identified in 22.1% (17/77) of stool samples from patients presenting at hospital with the gastrointestinal symptoms. This report of molecular identification of A. caninum DNA in human stools provide further support that intestinal infection with this parasite may be underreported in endemic areas.
Epidemiological and Clinical Profile of Fibromyalgia at the Kinshasa University Hospital : a Series of Clinical Cases
Authors: Mavinga Aldo Nzita , Mbuyi Jenny wa Mbuyi , Matanda Denis Tshitemb , Mulumba Christophe Badibanga , Nkodila Aliocha Natuhoyila , Lebughe Pierrot Litite , Mbuyi Jean-Marie Muamba , Malemba Jean-Jacques Kabasele 
Published: December 2022

Abstract
BACKGROUND. Fibromyalgia is a controversial and often underreported clinical entity in routine medical practice. The present study aimed to describe its epidemiological and clinical profile in patients attending the Kinshasa University Hospital.
METHODS. This is a series of clinical cases carried out in patients attending rheumatology practice at the Kinshasa University Hospital from December 2020 to March 2022. The following informations including age, sex, painful symptomatology, psychosomatic signs, the circumstances of the disease onset, factors that emphasize or reduce symptoms, the number of previous medical visits and, the impact on socio-professional life were collected. The diagnosis of fibromyalgia was defined according to the ACR 2010 criteria. Fibromyalgia was considered severe when it was associated with disability. Standard statistical tests were used to analyze the results.
RESULTS. 585 patients were followed during the study period. The diagnosis of fibromyalgia was retained in 63 of them, corresponding to a frequency of 10.8%. The sex ratio was 2 in favor of women and the mean age was 50.9±12.4 years. The mean diagnostic score was 17.6±3.6. Painful manifestations were dominated by arm involvement (84.1%). Fatigue was the most common psychosomatic manifestation (93.7%). Anxiety (41.3%) dominated the basic psychic state of patients and the average of previous medical visits number was 5.2±1.6. Fibromyalgia was often triggered by emotional stress (44.4%). Quiet rest (42.9%) was the main calming factor. 60.3% of patients developped the severe form of the disease.
CONCLUSION. Fibromyalgia is among common disease for which patients visit the rheumatology unit. So, it is required a special consideration from health care workers particularly rheumatologists for an early diagnosis.
Analysis of the glycolysis pathway in Enterocytozoon hepatopenaei after germination promotion and inhibition
Authors: Zhu Bo , Qian Dong , feng Juan , Sun Fuying , Jin Shan , Zhou Ying , Ma Rongrong , Chen Jiong 
Published: December 2022

Abstract
Enterocytozoon hepatopenaei (EHP) is an important factor limiting the growth of Penaeus vannamei. Its simple transmission route and lack of effective control drugs often lead to great losses for the shrimp aquaculture industry. In this study, some basic information of EHP was provided, including EHP spore purification, germination promoting treatment, quantification determination of the key genes expression, and the activities determination of key enzymes in glycolysis pathway at the stage of spore germination. The result showed that light microscopic and scanning electron microscopic analyses confirmed KOH promoted germination. The expression of the glyceraldehyde 3-phosphate dehydrogenase gene was stable, with high-level expression in treatment groups. Hexokinase gene expression and enzyme activity increased after promoting germination treatment. These findings indicated that the glycolytic pathway is enhanced during EHP germination. The results suggest that we can prevent EHP from invading host cells by attempting to block the energy supply.
On the usefulness of mock genomes to define heterotic pools, testers, and hybrid predictions in orphan crops.
Authors: Machado Ingrid , DoVale Júlio César , Sabadin Felipe , Fritsche-Neto Roberto 
Published: December 2022

Abstract
The advances in genomics in recent years have increased the accuracy and efficiency of breeding programs for many crops. Nevertheless, the adoption of genomic enhancement for several other crops essential in developing countries is still limited, especially for those that do not have a reference genome. These crops are more often called orphans. This is the first report to show how the results provided by different platforms, including the use of a simulated genome called the mock genome, can generate in population structure and genetic diversity studies, especially when the intention is to use this information to support the formation of heterotic groups, choice of testers and genomic prediction of single-crosses. For that, we used a method to assemble a reference genome to perform the SNP calling without needing an external genome. Thus, we compared the analysis results using the mock genome with the standard approaches (Array and GBS). The results showed that the GBS-Mock presented similar results to the standard methods of genetic diversity studies, division of heterotic groups, the definition of testers, and genomic prediction. These results showed that a mock genome constructed from the population's intrinsic polymorphisms to perform the SNP calling is an effective alternative for conducting genomic studies of this nature in orphan crops, especially those that do not have a reference genome.
Predictors of survival outcomes of different histopathological subtypes and stages of Wilms tumor treated following the SIOP 2001 Protocol, Pediatric Tertiary Care Centre Pakistan experience
Authors: Anjum Aysha , Hashim Imran , Goraya Amber , Sahrish Fariha , Ahmad Alia 
Published: December 2022

Abstract
Background:
Wilms tumor is the most common pediatric renal neoplasm. Following preoperative therapy, various histological subtypes, risks, and clinical stages are determined. The survival outcome of different subtypes is excellent depending upon the stage of the patient. In developed countries, overall survival and disease-free survival are excellent due to early presentation and closer follow-up.
Methods:
A retrospective study was conducted at the Pediatric Hematology/Oncology Department, Children’s Hospital Lahore. All diagnosed WT cases from 1st January 2014 who completed their treatment before 31st December 2018 was included. Entire management was based on SIOP 2001. Patients presenting before nephrectomy received four cycles of preoperative chemotherapy depending upon the clinical stage. After nephrectomy, the postoperative chemotherapy regimen was based on the stage, risk stratification, and metastatic status of the patient. The survival outcome of different histopathological subtypes, and stages were determined via Kaplan-Meier survival analysis, and the p-value was calculated via a log-rank test.
Results
The mean age of the 93 children was 44.4 months. The majority of the males (55.9%) were affected and commonly noted in the right-sided kidney (55.9%). The majority of patients completed the entire course of treatment (77.4%). The overall survival of all histological subtypes and stages was 77.4% and 77.1%, respectively. Event-free survival was 88.2% and 89.4%, respectively, at the 48-month-follow-up. Our study showed that febrile neutropenia is a major culprit affecting treatment outcomes.
Conclusions
The advanced stage presentation is quite typical in developing nations and contributes to the decreased OS and EFS seen in different histological subtypes and stages. In our study, OS significantly dropped from 45.3% in stage III to 12.9% in stage IV disease (P < 0.001). Despite belonging to a low-middle-income class country and uneducated background, the majority of the patients completed the entire course of treatment, and relapse was fairly rare. The perks of the current study are that our hospital is the only pediatric tertiary care center in Lahore, which has investigated a variety of parameters influencing the course of WT treatment over four years.
SCADA Authentication Identification Over The Next Generation CyberNet
Authors: Mughaid Ala , ALZU'BI SHADI , AlZioud Adel , Ghazo Alaa Al 
Published: December 2022

Abstract
SCADA (supervisory control and data acquisition) system is an advanced control system used in industrial and service sectors such as oil and gas, water treatment, nuclear energy, and electrical power generation to control and monitor the manufacturing or servicing process and maintain the process within predetermined values in order to induce desirable outcomes.
The SCADA architecture employs several protocols, including Modbus/RTU, Modbus TCP/IP, DNP3 and IEC60870. This paper will concentrate on the most widely used protocol in SCADA systems, Modbus TCP/IP, due to its widespread use, simplicity, and robustness. SCADA systems are vulnerable to cyber-attacks because Modbus/TCP lacks security measures for access control, authentication, and confidentiality. The paper contains valuable contribution by introducing an authentication technique to check the validity of messages in which the authorized users only pass this check, thereby adding a security measure to the SCADA system in terms of cyber-attacks.
Association Between Changes in Serum Alkaline Phosphatase Levels and Radiographic Progression in Ankylosing Spondylitis
Authors: Kim Tae-Hwan , Park Seo Young , Shin Ji Hui , Lee Seunghun , Joo Kyung Bin , Koo Bon San 
Published: December 2022

Abstract

This retrospective study evaluated the electronic medical records of patients with ankylosing spondylitis (AS) between January 2001 and December 2018 to determine the relationship between serum alkaline phosphatase (ALP) levels and radiographic changes over time. Longitudinal data including serum ALP levels were imputed by linear interpolation at 3-month intervals. Among the serum ALP levels for 8 years prior to modified Stoke Ankylosing Spondylitis Spinal Score (mSASSS) measurement, the serum ALP level having the highest beta coefficient with the mSASSS was selected. Linear mixed models with the selected serum ALP levels, mSASSS, and clinical variables were investigated. We included 1122 patients, with a mean follow-up period of 8.20 (standard deviation: 2.85) years. The serum ALP level from 5 years and 3 months prior showed the highest beta coefficient with the mSASSS. In the linear mixed model, the serum ALP level 5 years and 3 months before radiographic changes was significantly associated with the mSASSS (β = 0.021, 95% confidence interval: 0.017–0.025,p < 0.001). Serum ALP levels measured approximately 5 years before may be a surrogate marker for predicting spinal radiographic changes. Long-term prospective clinical and experimental studies of > 5 years are required for biomarker discovery or therapeutic research on AS radiographic progression.