CSF proteomics identifies early changes in autosomal dominant Alzheimer's disease.

In this high-throughput proteomic study of autosomal dominant Alzheimer's disease (ADAD), we sought to identify early biomarkers in cerebrospinal fluid (CSF) for disease monitoring and treatment strategies. We examined CSF proteins in 286 mutation carriers (MCs) and 177 non-carriers (NCs). The developed multi-layer regression model distinguished proteins with different pseudo-trajectories between these groups. We validated our findings with independent ADAD as well as sporadic AD datasets and employed machine learning to develop and validate predictive models. Our study identified 137 proteins with distinct trajectories between MCs and NCs, including eight that changed before traditional AD biomarkers. These proteins are grouped into three stages: early stage (stress response, glutamate metabolism, neuron mitochondrial damage), middle stage (neuronal death, apoptosis), and late presymptomatic stage (microglial changes, cell communication). The predictive model revealed a six-protein subset that more effectively differentiated MCs from NCs, compared with conventional biomarkers.

Mitigation of Anti-Drug Antibody Production for Augmenting Anticancer Efficacy of Therapeutic Protein via Co-Injection of Nano-Rapamycin.

The induction of anti-drug antibody (ADA) is a formidable challenge for protein-based therapy. Trichosanthin (TCS) as a class of ribosome-inactivating proteins is widely studied in tumor treatment. However, the immunogenicity can induce the formation of ADA, which can cause hypersensitivity reactions and neutralize the efficacy of TCS, thus limiting its clinical application in cancer therapy. Here, a promising solution to this issue is presented by co-administration of the rapamycin nanoparticles and TCS. PEGylated rapamycin amphiphilic molecule is designed and synthesized as a prodrug and a delivery carrier, which can self-assemble into a nanoparticle system with encapsulation of free rapamycin, a hydrophobic drug. It is found that co-injection of the PEGylated rapamycin nanoparticles and TCS could mitigate the formation of anti-TCS antibody via inducing durable immunological tolerance. Importantly, the combination of TCS and the rapamycin nanoparticles has an enhanced effect on inhibit the growth of breast cancer. This work provides a promising approach for protein toxin-based anticancer therapy and for promoting the clinical translation.

Simultaneous detection of multi-channel signals in MHz bandwidth using nitrogen-vacancy centers in a diamond.

In this paper, we propose a method for simultaneously recovering multiple radio wave signals based on nitrogen-vacancy (NV) centers in diamond combining optically detected magnetic resonance (ODMR) spectrum. A controlled magnetic field gradient applied to the laser excitation area on the surface of diamond widens the detectable ODMR bandwidth to 200 MHz. Three different frequency-modulated (FM) signals with distinct carrier frequencies falling within the resonance frequency range are received and demodulated in real-time. Subsequently, the FM signal reception capability of this system is further investigated by measuring baseband signal frequencies ranging from 0.1 Hz to 200 Hz and adjusting the carrier power within a dynamic range from -10 dBm to 30 dBm. This proposal, which accomplishes multi-channel demodulation using a compact and single device, has potential applications in fields such as wireless communication, radar and navigation.

Efficacy of azithromycin combined with intravenous immunoglobulin in the treatment of refractory mycoplasma pneumoniae pneumonia in children: a meta-analysis.

BACKGROUND: The incidence of refractory Mycoplasma pneumoniae pneumonia (RMPP) in children is increasing, posing a serious threat to life safety. Intravenous immunoglobulin (IVIG) has demonstrated the ability to modulate the immune system and has shown the potential to treat RMPP. This study evaluated the clinical efficacy and safety of azithromycin combined with IVIG in the treatment of RMPP in children through a meta-analysis. METHODS: A comprehensive search was conducted in seven databases including PubMed and Cochrane Library, and the studies on the treatment of RMPP in children with azithromycin combined with IVIG were screened. After data extraction, meta-analysis and sensitivity analysis were performed to assess heterogeneity and stability. RESULTS: Thirteen randomized controlled trials and two cohort studies were included, totaling 1,142 children. The results of meta-analysis showed a higher clinical efficacy rate (RR = 1.18, 95% CI: 1.11-1.25, P < 0.01) and shorter time to defervescence (MD = -2.12, 95% CI: -2.69--1.55), time to disappearance of pulmonary rales (MD = -2.90, 95% CI: -3.57--2.23), time to disappearance of cough (MD = -3.59, 95% CI: -4.51--2.67), and hospital length of stay (MD = -5.72, 95% CI: -8.80--2.64) in the experimental group receiving azithromycin combined with IVIG treatment compared to the control group treated with azithromycin alone. Additionally, there was no significant publication bias in this meta-analysis. CONCLUSION: Treatment with azithromycin combined with IVIG is more effective than treatment with azithromycin alone for children with RMPP. CLINICAL TRIAL NUMBER: Not applicable.

Analysis of the Genomic Sequences and Metabolites of Bacillus velezensis YA215.

Discovering more novel antimicrobial compounds has become a keen research problem. In this study, YA215 genome was sequenced by the Illumina HiSeq + PacBio sequencing platform. Genome assembly was performed by Unicycler software and the gene clusters responsible for secondary metabolite biosynthesis were predicted by antiSMASH. The genome comprised 3976514 bp and had a 46.56% G + C content. 3809 coding DNA sequences, 27 rRNAs, 86 tRNAs genes, and 79 sRNA were predicted. Strain YA215 was re-identified as Bacillus velezensis based on ANI and OrthoANI analysis. In the COG database, 23 functional groups from 3090 annotations were predicted. In the GO database, 2654 annotations were predicted. 2486 KEGG annotations linked 41 metabolic pathways. Glycosyl transferases, polysaccharide lyases, auxiliary activities, glycoside hydrolases, carbohydrate esterases, and carbohydrate-binding modules were predicted among the 127 annotations in the CAZy database. AntiSMASH analysis predicted that B. velezensis YA215 boasted 13 gene clusters involved in synthesis of antimicrobial secondary metabolites including surfactin, fengycin, macrolactin H, bacillaene, difficidin, bacillibactin, bacilysin, and plantazolicin. Three of the gene clusters (gene cluster 5, gene cluster 9, and gene cluster 10) have the potential to synthesize unknown compounds. The research underscore the considerable potential of secondary metabolites, identified in the genomic composition of B. velezensis YA215, as versatile antibacterial agents with a broad spectrum of activity against pathogenic bacteria.

Factors influencing the job embeddedness of new graduate nurses: A multicentre cross-sectional study.

AIM: To identify factors associated with job embeddedness from the perspective of retaining new graduate nurses. DESIGN: The study was cross-sectional in design. METHODS: Convenience and stratified sampling were used to recruit 415 newly graduated nurses from 12 tertiary hospitals in China. Anonymized data were collected through self-designed sociodemographic questionnaires, job embeddedness scale, feedback-seeking behaviour scale, authentic leadership perception scale and decent work scale. Appropriate indicators were used for descriptive statistics and t-tests, ANOVA, Pearson correlation analysis and multiple linear regression to examine the influencing factors. RESULTS: The study showed that monthly income level, decent labour, authentic leadership and feedback-seeking behaviour were significant predictors of job embeddedness among new graduate nurses. CONCLUSION: The job embeddedness of new graduate nurses is moderate. Nursing managers need to construct reasonable and fair compensation incentives, adopt positive leadership styles and encourage proactive feedback-seeking behaviours to improve the job embeddedness of new graduate nurses and alleviate the nursing talent shortage. IMPACT: Exploring the factors influencing the job embeddedness of new graduate nurses provides a reference for establishing new graduate nurse retention strategies to help promote the career development of new graduate nurses and alleviate the nursing brain drain. REPORTING METHOD: We adhered to the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) guidelines. PATIENT OR PUBLIC CONTRIBUTION: No patient or public contribution.

Effects of the promoting bacterium on growth of plant under cadmium stress.

Cadmium (Cd) pollution is a huge threat to ecosystem health. In the manuscript, pot experiments were conducted to investigate the changes in plant biomass and antioxidant indicators under different cadmium pollution levels (0, 25, 50, and 100 mg/kg) of inoculation of plant growth-promoting bacteria ZG7 on sugar beet. The results showed that the accumulation of excess Cd in sugar beet exhibited different symptoms, including reduced biomass (p < 0.05). Compared with the group treated with uninoculated strain ZG7, inoculation of strain ZG7 significantly reduced the toxicity of sugar beet to Cd and enhanced its antioxidant capacity, with no significant differences in root biomass and increases in leaf biomass of 15.71, 5.84, and 74.12 under different Cd concentration treatments (25, 50, and 100 mg/kg), respectively. The root enrichment of Cd was reduced by 49.13, 47.26, and 21.50%, respectively (p < 0.05). The leaf fraction was reduced by 59.35, 29.86, and 30.99%, respectively (p < 0.05). In addition, the enzymatic activities of sucrase, urease, catalase, and neutral phosphatase were significantly enhanced in the soil (p < 0.05). This study helps us to further investigate the mechanism of cadmium toxicity reduction by inoculated microorganisms and provides a theoretical reference for growing plants in cadmium-contaminated agricultural fields.

The combination of microorganisms and phytoremediation is becoming a popular research topic. The selection of suitable plant growth promoting bacteria can not only promote the growth and development of plants and enhance their cadmium resistance, but also improve the soil quality. And the results of this study will be important for growing edible plants and improving soils in cadmium-contaminated areas.

"Discovering shine through feedback seeking"---feedback seeking among new graduate nurses: a qualitative study.

BACKGROUND: Feedback is critical to improving practitioners' clinical practice and professional growth. Although they are still considered junior practitioners, their feedback-seeking experiences have yet to be investigated. This study aimed to understand the fundamental thoughts and experiences of new graduate nurses regarding feedback-seeking and to identify the main factors that influence their feedback-seeking behaviors. METHODS: Conducting a descriptive phenomenological study, semi-structured in-depth interviews with newly graduated nurses from four hospitals in Zhejiang Province, China, face-to-face or via video call in the hospital conference room through purposive and snowball sampling. Interview data were evaluated using Colaizzi's 7-step phenomenological data analysis. The COREQ checklist was followed. RESULTS: A total of 15 new graduate nurses were interviewed as a sample, and 13 categories emerged from our data. They were categorized into four central elements: (1) perceptions and attitudes, (2) drivers, (3) dilemmas and needs, and (4) transformation and growth. CONCLUSIONS: This study found that new graduate nurses have various needs but face dilemmas in the feedback-seeking process. Nursing managers should be proficient at providing positive leadership, collaborating with clinical mentors to foster an atmosphere where new graduate nurses may obtain honest, transparent, and fair feedback, and exercising caution when providing negative feedback.

Effects of branched-chain amino acids on surfactin structure and antibacterial activity in Bacillus velezensis YA215.

Antibiotics are essential for combating pathogens; however, their misuse has led to increased resistance, necessitating the search for effective, low-toxicity alternatives. Surfactin, a cyclic lipopeptide with a C12-C17 ß-hydroxy fatty acid chain, exhibits significant antibacterial activity and resists resistance, making it a research focus. Nonetheless, the effects of branched-chain amino acids (BCAAs) on surfactin's structure and activity are not well understood. This study examines the influence of BCAAs (L-valine, L-leucine, and L-isoleucine) on the lipopeptide (surfactin) produced by Bacillus velezensis YA215. Process optimization shows that adding 1 g/L of L-Leu and L-Ile, and 0.5 g/L of L-Val, maximized surfactin production to 18.59%, 19.23%, and 20.64%, respectively. Surfactin content peaked at 36 h with L-Val and L-Ile, yielding 19.72% and 11.37%. In contrast, L-Leu addition peaked at 24 h, yielding 11.33%. Notably, L-Val supplementation resulted in the highest relative surfactin content. Antimicrobial testing demonstrated that BCAAs significantly enhance the antibacterial effects of lipopeptides against Escherichia coli and Staphylococcus aureus, with Val showing the most pronounced effect. The addition of BCAAs notably altered the composition of surfactin fatty acid chains. Specifically, Val increased the proportions of iso C14 and iso C16 ß-hydroxy fatty acids from 13.3% and 4.216-23.803% and 8.31%, respectively. Additionally, the amino acid composition at the 7th position of the peptide chain changed significantly, especially with Val addition, which increased the proportion of C14 [Val 7] surfactin by 3.29 times. These structural changes are likely associated with the enhanced antibacterial activity of surfactin. These findings provide valuable insights into the roles of BCAAs in microbial fermentation, underscoring their importance in metabolic engineering to enhance the production of bioactive compounds.

Molecular epidemiology and genetic diversity of norovirus among hospitalized patients with acute gastroenteritis in Shandong, China, 2016-2018.

Norovirus (NoV) infection is a leading cause of acute gastroenteritis (AGE) for people of all ages. Here, we reported the molecular epidemiology and genetic diversity of NoVs among hospitalized patients with AGE between 2016 and 2018 in Shandong Province, China. Two thousand sixty-nine AGE patients from sentinel hospitals were enrolled. The stool samples were collected and tested for NoVs by real-time RT-PCR. The RNA-dependent RNA polymerase (RdRp) and capsid gene of 163 strains were amplified and sequenced for genotyping. Phylogenetic analyses and genomic characterization were conducted with the VP1 and RdRp region of the full genome sequences. Four hundred seventy two (21.76%) samples were NoV-positive. The positive rate in 2016 was higher than those of 2017 and 2018. We observed diverse NoV genotypes. GII.2[P16] emerged in January 2017 and became the dominant genotype between May and June 2017. Phylogenetic analyses showed that our GII.2[P16] genomes clustered in the SC1 in VP1 region, while they belonged to the Emerging GⅡ.P16 (2015-2017) clade in RdRp region. Our GⅡ.4 strains displayed two amino acid mutations, positions R297H and D372N, in epitope A of the VP1 region. Our study highlighted that NoV is an important pathogen of viral AGE in Shandong and, therefore, it is necessary to strengthen its surveillance.

Inoculation of Exogenous Complex Bacteria to Enhance Resistance in Alfalfa and Combined Remediation of Heavy Metal-Contaminated Soil.

Heavy metals are considered to be one of the main sources of soil contamination. In this study, three tolerant bacteria were isolated from the heavy metal-contaminated soil in mining area, and immobilized bacteria were constructed using corn straw as the carrier. The combined remediation effect of immobilized bacteria and alfalfa in pot experiments was explored in heavy metal-contaminated soil. Under heavy metal stress, inoculation with immobilized bacteria significantly promoted the growth of alfalfa, in which the dry weights of roots, stems, and leaves increased by 19.8, 6.89, and 14.6%, respectively (P < 0.05). Also, inoculation with immobilized bacteria improved the antioxidant capacity of plants and the activity of soil enzymes and improved soil quality (P < 0.05). Microbial-phytoremediation technology effectively reduced the heavy metal content in the soil, and can restore the soil contaminated by heavy metals. The results will help to further understand the mechanism of microbial inoculation to reduce the toxicity of heavy metals, and provide guidance for the cultivation of forage grasses in heavy metal-contaminated soils.

Transcriptome Characterization of Pigment-Related Genes in Jujube (Ziziphus Jujuba Mill.) Peel at Different Growth Stages.

One of the most important qualities of jujube fruit is its color. Chlorophyll, carotenoid, and anthocyanin all play important roles in the coloring of jujube fruit. However, few studies have focused on the pigment molecular mechanism. In the present study, jujube peels of 'Sanbianhong' in three growth stages were evaluated for their gene expression characteristics and gene regulation related to pigment formation using the transcriptome sequencing analysis. A total of 84.86 Gb of clean data were obtained in the analysis. In the FS1 vs. FS3, FS1 vs. FS5, and FS3 vs. FS5, 4,530, 11,012, and 9,072 differentially expressed genes (DEGs) were identified, respectively. The inter-group screening among the three comparisons yielded 1430 common DEGs. Among these DEGs, 27, 16, and 28 genes were enriched in chlorophyll, carotenoid, and anthocyanin metabolic pathways, respectively. Twelve genes were chosen at random, and the accuracy of the transcriptome data were confirmed using qRT-PCR. The molecular mechanism underlying the pigmentation of jujube fruit was elucidated at the transcriptome level, which would provide a scientific basis for the subsequent functional studies on the color-regulating genes of jujube fruits.

Prediction of Tinnitus Treatment Outcomes Based on EEG Sensors and TFI Score Using Deep Learning.

Tinnitus is a hearing disorder that is characterized by the perception of sounds in the absence of an external source. Currently, there is no pharmaceutical cure for tinnitus, however, multiple therapies and interventions have been developed that improve or control associated distress and anxiety. We propose a new Artificial Intelligence (AI) algorithm as a digital prognostic health system that models electroencephalographic (EEG) data in order to predict patients' responses to tinnitus therapies. The EEG data was collected from patients prior to treatment and 3-months following a sound-based therapy. Feature selection techniques were utilised to identify predictive EEG variables with the best accuracy. The patients' EEG features from both the frequency and functional connectivity domains were entered as inputs that carry knowledge extracted from EEG into AI algorithms for training and predicting therapy outcomes. The AI models differentiated the patients' outcomes into either therapy responder or non-responder, as defined by their Tinnitus Functional Index (TFI) scores, with accuracies ranging from 98%-100%. Our findings demonstrate the potential use of AI, including deep learning, for predicting therapy outcomes in tinnitus. The research suggests an optimal configuration of the EEG sensors that are involved in measuring brain functional changes in response to tinnitus treatments. It identified which EEG electrodes are the most informative sensors and how the EEG frequency and functional connectivity can better classify patients into the responder and non-responder groups. This has potential for real-time monitoring of patient therapy outcomes at home.

A novel prognostic index for sporadic Burkitt lymphoma in adult patients: a real-word multicenter study.

BACKGROUND: Adult sporadic Burkitt lymphoma (BL) is a rare but highly aggressive subtype of lymphoma which lacks its own unique prognostic model. Systemic inflammatory biomarkers have been confirmed as prognostic markers in several types of malignancy. Our objective was to explore the predictive value of pretreatment inflammatory biomarkers and establish a novel, clinically applicable prognostic index for adult patients with sporadic BL. METHODS: We surveyed retrospectively 336 adult patients with newly diagnosed sporadic BL at 8 Chinese medical centers and divided into training cohort (n = 229) and validation cohort (n = 107). The pretreatment inflammatory biomarkers were calculated for optimal cut-off value. The association between serum biomarkers and overall survival (OS) was analyzed by Kaplan-Meier curves and Cox proportional models. The risk stratification was defined based on normal LDH level, Ann Arbor stage of I and completely resected abdominal lesion or single extra-abdominal mass < 10 cm. RESULTS AND CONCLUSIONS: Univariate and multivariate analyses revealed that platelets< 254 × 109/L, albumin< 40 g/L, lactate dehydrogenase≥334 U/L independently predicted unfavorable OS. We used these data as the basis for the prognostic index, in which patients were stratified into Group 1 (no or one risk factor), Group 2 (two risk factors), or Group 3 (three risk factors), which were associated with 5-year OS rates of 88.1, 72.4, and 45%, respectively. In the subgroup analysis for high-risk patients, our prognostic model results showed that high-risk patients with no more than one adverse factor presented a 5-year survival rate of 85.9%, but patients with three adverse factors had a 5-year survival rate of 43.0%. Harrell's concordance index (C-index) of the risk group score was 0.768. Therefore, the new prognostic model could be used to develop risk-adapted treatment approaches for adult sporadic BL.

Detection of Escherichia coli using luminometer with pyruvate kinase.

Portable and quantitative detection of Escherichia coli (E. coli) has the potential to reform clinical diagnostics, food safety, and environmental monitoring. At present, most commercial devices used for pathogen detection have disadvantages such as expensive, highly complex operations, or limited detection specificity. Using the common luminometer and the properties of pyruvate kinase utilizing phosphoenolpyruvate to generate adenosine triphosphate (ATP), we have developed a method that could specifically quantify E. coli. The system is based on a sandwich hybridization procedure wherein both oligonucleotide probes recognize each end of the target of pathogenic 16S rRNAs segment. The detection probe DNA-conjugated pyruvate kinase can link ATP production to the detection of pathogenic nucleic acid in the samples. The luminometer-based system is capable of detecting E. coli with single bacteria resolution. The platform should be easily used to the detection of many other toxic analytes through the application of suitable functional-DNA recognition elements.

Gold nanoparticles-mediated fluorescent chemical nose sensor for pathogenic diagnosis and phenotype.

Pathogens are one of the important factors affecting national economic construction. An ideal detection system for pathogen control with excellent sensitivity, high specificity, and time-saving is needed. Here, we reported a method for bacterial detection using gold nanoparticles-mediated fluorescent "chemical nose" sensors (GFCEs). The technique consists of gold nanoparticles-coated magnetic particle using benzaldehyde, octyl aldehyde, and pyrimidine-4-formaldehyde modified, respectively. And these positively charged nanocompound interacting with three different fluorescent proteins (FPs) to form three kinds of GFCEs, respectively, named GFCE1, GFCE2, and GFCE3. Upon binding with pathogenic cells, functionalized gold nanoparticles could identify patches on hydrophobic/functional surfaces of microorganisms, and self-assemble with living bacteria by complementary electrostatic interactions. The binding ability between GFCEs and bacteria determines the change of fluorescence response of three FPs from GFCEs. These feature fluorescent level are pathogen-specific, highly repeatable, and can be analyzed by Linear Discriminant Analysis (LDA). The combination of GFCE1 and GFCE2 has the best performance when detecting pathogens with concentrations of 106 cfu mL-1 . The first discriminant within 15 minutes is 93.8%, which could be used for subsequent identification of unknown samples. The commonly applicable system provides a simple way for the rapid bacterial detection without preprocessing procedures.

Effects of heavy metals on bacterial community structures in two lead-zinc tailings situated in northwestern China.

We evaluated the variations of bacterial communities in six heavy metal contaminated soils sampled from Yanzi Bian (YZB) and Shanping Cun (SPC) tailings located in northwestern China. Statistical analysis showed that both the heavy metals and soil chemical properties could affect the structure and diversity of the bacterial communities in the tailing soils. Cd, Cu, Zn, Cr, Pb, pH, SOM (soil organic matters), TP (total phosphorus) and TN (total nitrogen) were the main driving factors of the bacterial community variations. As a consequence, the relative abundances of certain bacterial phyla including Proteobacteria, Chloroflexi, Firmicutes, Nitrospirota and Bacteroidota were significantly increased in the tailing soils. Further, we found that the abundance increasement of these phyla were mainly contributed by certain species, such as s__unclassified_g__Thiobacillus (Proteobacteria), s__unclassified_g__Sulfobacillus (Firmicutes) and Leptospirillum ferriphilum (Nitrospirota). Thus, these species were considered to be strongly heavy metal tolerant. Together, our findings will provide a useful insight for further bioremediations of these contaminated areas.

Facile decoration of two-dimensional Ti3C2Txnanoplates with CuS nanoparticles via a facilein situsynthesis strategy at room temperature for superhigh specific capacitance of supercapacitors.

Although supercapacitors have attracted more and more attention owing to their fast charging speed and high power density, their wide applications have still been limited by their low energy density. In this study, a new CuS-nanoparticle-decorated Ti3C2Txelectrode material is fabricated via a facilein situsynthesis strategy at room temperature. CuS nanoparticles, generated from thein situreaction of Cu (NO3)2·3H2O with Na2S·9H2O, are anchored between the Ti3C2Txinterlayers through electrostatic interaction. This type of structural construction is found capable of not only reducing the surface oxidation of Ti3C2Tx, but also preventing the accumulation of CuS nanoparticles by the template effect of Ti3C2Txnanoplates. As a result, the CuS/Ti3C2Txnanohybrid delivers a maximum specific capacitance of 911 F g-1at 1 A g-1and a good cycling stability. A symmetric supercapacitor fabricated using the CuS/Ti3C2Txnanohybrid as the electrode material exhibits an energy density of 43.56 W h kg-1with a power density of 475 W kg-1. Consequently, this work provides a new perspective of microstructural design for the preparation of electrode materials with superhigh specific capacitance through an easy and low-costin situ-reaction method at room temperature.

Isolated Central Nervous System Blast Crisis of Chronic Myeloid Leukemia with Dasatinib Therapy.

BACKGROUND: Isolated central nervous system (CNS) blast crisis was uncommon in chronic myeloid leukemia (CML). METHODS: The present study reported an interesting case of a CML patient administered with dasatinib presenting with headache and seizure unconsciousness. Imaging investigation, immunophenotyping, bone marrow cytology inspection, chromosomal analysis, and polymerase chain reaction (PCR) were performed on a 41-year-old CML patient. RESULTS: Bone marrow examination revealed complete cytogenetic remission and there were no obvious abnormalities in head CT and MR. Cytomorphological examination of cerebrospinal fluid (CSF) showed 50% blasts. Flow cytometry analysis was showed 78.3% CSF cells expressing the specific myeloid antigens. PCR analysis on CSF cells was positive for BCR/ABL P210 fusion gene. All the above CSF findings were suggestive of CNS infiltrating isolated from bone marrow cytogenetic remission. CONCLUSIONS: Isolated CNS blast crisis of CML with dasatinib were rare. The mechanism still remains unclear and the treatment regimen requires further exploration. Flow cytometry showed great value to detect the blast cells in this patient.

Immunogenomic pathways associated with cytotoxic lymphocyte infiltration and survival in colorectal cancer.

BACKGROUND: Colorectal cancer (CRC) is the second leading cancer killer in the US today and patients with metastatic disease have only a 14% 5-year survival. One of the most impactful recent advances in cancer therapy, immune checkpoint inhibition, has not been shown to be effective for the majority of these patients. In this study, we use The Cancer Genome Atlas (TCGA) and recently developed informatic-based tools to identify targets for immune based therapy in colorectal cancer patients. METHODS: Open access, pre-processed (level 3) mRNA data and clinical data from colorectal patients from the TCGA was downloaded from FireCloud. Using the Microenvironment Cell Populations-Counter method (MCP-Counter), cytotoxic lymphocyte scores were calculated for all patients. Patients were then grouped by cytotoxic lymphocyte score (High vs Low), pathologic stage, and location to identify differentially expressed genes. Pathway enrichment analysis was performed using Reactome to determine differentially expressed genes associated with immune pathways. Survival analysis was performed with identified differentially expressed genes. RESULTS: In the TCGA dataset, there are 461 colon and 172 rectal cancer patients. After stratifying patients by cytotoxic lymphocyte score, anatomical location, and stage, we found a significant number of differentially expressed genes. We identified one pathway, "immunoregulatory interactions between a lymphoid and non-lymphoid cell", that was highly enriched and included in all tumor locations and stages. Survival analysis performed with differentially expressed genes in this pathway identified 21 different genes associated with survival and cytotoxic lymphocyte infiltration, with ~ 70% of these genes occurring in the metastatic right-sided CRC group. Specifically, all genes associated with survival in the metastatic right-sided colorectal cancer group with low cytotoxic lymphocyte scores positively impacted survival. CONCLUSIONS: Utilizing the TCGA, a publicly available dataset, and informatics-based analyses, we identified potential targets to improve immune based therapy in colorectal cancer. Additionally, we note the most targets in metastatic right-sided CRC patients, the patient group with the worst predicted survival. The results from this study demonstrate the ability of informatics-based analytic techniques to identify new therapeutic targets as well as improve patient selection for intervention, helping us to achieve the goals of precision-based oncology.