bluuebunny/crossref_metadata_2025_split huggingface dataset:
MYC Overexpression Drives Immune Evasion in Hepatocellular Carcinoma That Is Reversible through Restoration of Proinflammatory Macrophages
Authors: Dhanasekaran Renumathy , Hansen Aida S. , Park Jangho , Lemaitre Lea , Lai Ian , Adeniji Nia , Kuruvilla Sibu , Suresh Akanksha , Zhang Josephine , Swamy Varsha , Felsher Dean W. 
Published: December 2022

AbstractCancers evade immune surveillance, which can be reversed through immune-checkpoint therapy in a small subset of cases. Here, we report that the MYC oncogene suppresses innate immune surveillance and drives resistance to immunotherapy. In 33 different human cancers, MYC genomic amplification and overexpression increased immune-checkpoint expression, predicted nonresponsiveness to immune-checkpoint blockade, and was associated with both Th2-like immune profile and reduced CD8 T-cell infiltration. MYC transcriptionally suppressed innate immunity and MHCI-mediated antigen presentation, which in turn impeded T-cell response. Combined, but not individual, blockade of PDL1 and CTLA4 could reverse MYC-driven immune suppression by leading to the recruitment of proinflammatory antigen-presenting macrophages with increased CD40 and MHCII expression. Depletion of macrophages abrogated the antineoplastic effects of PDL1 and CTLA4 blockade in MYC-driven hepatocellular carcinoma (HCC). Hence, MYC is a predictor of immune-checkpoint responsiveness and a key driver of immune evasion through the suppression of proinflammatory macrophages. The immune evasion induced by MYC in HCC can be overcome by combined PDL1 and CTLA4 blockade.Significance:Macrophage-mediated immune evasion is a therapeutic vulnerability of MYC-driven cancers, which has implications for prioritizing MYC-driven hepatocellular carcinoma for combination immunotherapy.
Prospective and Cross-sectional Associations of the Rectal Tissue Microbiome with Colorectal Adenoma Recurrence
Authors: Byrd Doratha A. , Vogtmann Emily , Ortega-Villa Ana M. , Wan Yunhu , Gomez Maria , Hogue Stephanie , Warner Andrew , Zhu Bin , Dagnall Casey , Jones Kristine , Hicks Belynda , Albert Paul S. , Murphy Gwen , Sinha Rashmi 
Published: December 2022

AbstractBackground:The gut microbiome is plausibly associated with colorectal cancer risk; however, previous studies mostly investigated this association cross-sectionally. We investigated cross-sectional and prospective associations of the rectal tissue microbiome with adenoma recurrence in the Polyp Prevention Trial (PPT).Methods:PPT is a 4-year randomized clinical trial of the effect of a dietary intervention on adenoma recurrence among community members. We extracted DNA from rectal biopsies at baseline, end of year 1, and end of year 4 among 455 individuals and sequenced the V4 region of the 16S rRNA gene. At each timepoint, we investigated associations of alpha diversity, beta diversity, and presence and relative abundance of select taxa with adenoma recurrence using multivariable logistic regression.Results:Variation in beta diversity was primarily explained by subject and minimally by year of collection or time between biopsy and colonoscopy. Cross-sectionally, year 4 alpha diversity was strongly, inversely associated with adenoma prevalence [ORQ3 vs. Q1 Shannon index = 0.40 (95% confidence interval, CI: 0.21–0.76)]. Prospective alpha diversity associations (i.e., baseline/year 1 alpha diversity with adenoma recurrence 3–4 years later) were weak or null, as were cross-sectional and prospective beta diversity–adenoma associations. Bacteroides abundance was more strongly, positively associated with adenoma prevalence cross-sectionally than prospectively.Conclusions:Rectal tissue microbiome profiles may be associated with prevalent adenomas, with little evidence supporting prospective associations.Impact:Additional prospective studies, with serial fecal and tissue samples, to explore microbiome-colorectal cancer associations are needed. Eventually, it may be possible to use microbiome characteristics as intervenable risk factors or screening tools.
The Interplay of Cesarean-Section Delivery and First-Birth Order as Risk Factors in Acute Lymphoblastic Leukemia
Authors: Pombo-de-Oliveira Maria S. ,   for the EMiLI Study Group, Petridou Eleni Th. , Karalexi Maria A. , Junqueira Maria Elizangela Ramos , Braga Flávio Henrique Paraguassu , Bouzas Luis Fernando , Murra Glaucia Regina Costa , Lopes Luiz Fernando , Ntzani Evangelia , Greaves Mel 
Published: December 2022

AbstractBackground:Childhood B-cell precursor acute lymphoblastic leukemia (BCP-ALL) has been associated with early-life exposures, including birth by cesarean section (C-section), and a deficit of social exposure (first child). These exposures as proxies for microbiome acquisition in infancy are essential to prime the immune system and restrain later dysregulated immune responses that can trigger ALL in susceptible individuals. We tested risk factors pertaining to immune stimulation that may impact BCP-ALL development.Methods:Cases comprised 1,126 children (0–12 years) with ALL (BCP-ALL: 78.5%) from the EMiLI study group in Brazil (2002–2020). Age- and sex-matched controls (n = 2,252) were randomly selected from healthy children whose mothers participated in the National Placental and Umbilical Cord Blood Bank donation. Multiple logistic regression was run fitted and adjusted for selected covariates models.Results:C-section delivery was associated with increased risk for ALL [odds ratio (OR) ALL: 1.10; 95% confidence intervals (CI), 1.04–1.15; ORBCP-ALL: 1.09; 95% CI, 1.03–1.14], as well as being the firstborn child. Interaction analysis showed a significant effect of first birth on the observed C-section associations (P &lt; 0.0001). Indeed, high-risk children, namely, firstborn children delivered via C-section were at increased risk for ALL (OR: 2.33; 95% CI, 2.40–4.84) compared with non-first, vaginally born children. An increased risk was found for firstborn children delivered by C-section and non-breastfed with ALL (ORALL: 2.32; 95% CI, 1.27–4.24; ORBCP-ALL: 2.37; 95% CI, 1.18–4.76).Conclusions:Our observations are in accord with the prediction that exposures determining microbiome composition and adrenal pathway in infancy contribute to the risk of BCP-ALL.Impact:These findings encourage the exploration of potential preventive interventions.See related commentary by Wiemels and Gallant, p. 292
Factors Related to Human Papillomavirus Positivity among Oral Cavity and Pharynx Cancers from Surveillance, Epidemiology and End Results (SEER) Program Data
Authors: Jordan Kelsey H. , Fisher James L. , Stephens Julie A. , Paskett Electra D. 
Published: December 2022

AbstractBackground:As human papillomavirus positive (HPV+) oral cavity and pharynx cancer (OCPC) incidence increases significantly, our objective was to determine whether selected sociodemographic and clinical factors were associated with HPV+ OCPCs overall and by oropharyngeal and non-oropharyngeal sites.Methods:Surveillance, Epidemiology and End Results (SEER) Program data were used in this study. Specifically, univariate and logistic regression models were used to examine the relationships between HPV+ and HPV− OCPC cases and age, sex, race, ethnicity, marital status, factors of neighborhood socioeconomic status (i.e., nSES/Yost index) and rurality/urbanity, first malignancy status, histology, reporting source, stage at diagnosis, and OCPC anatomic site. The same approach was used to identify risk factors for HPV positivity for oropharyngeal and non-oropharyngeal OCPCs separately.Results:In all OCPCs, cases that were male, &lt;80 years old, lived in the four highest nSES categories, diagnosed with a non-“gum and other mouth” OCPC (ref = hypopharynx), not locally staged at diagnosis, and a first malignancy had higher odds of being HPV+. Cases that were American Indian/Alaska Native and Asian or Pacific Islander (ref = White), Spanish-Hispanic-Latino ethnicity, non-married/partnered, and not reported by a hospital/clinic had lower odds of being HPV+. Associations were maintained in oropharyngeal OCPCs and only age and race remained significant for non-oropharyngeal OCPCs.Conclusions:Sociodemographic and clinical differences in HPV+ and HPV− OCPC, overall and for (non)oropharyngeal, cases exist.Impact:Identification of OCPC and (non)oropharyngeal risk factors for HPV positivity may assist in discovering high-risk groups that should receive enhanced public health efforts to reduce the U.S. OCPC burden.
Gut Microbiota-Generated Phenylacetylglutamine and Heart Failure
Authors: Romano Kymberleigh A. , Nemet Ina , Prasad Saha Prasenjit , Haghikia Arash , Li Xinmin S. , Mohan Maradumane L. , Lovano Beth , Castel Laurie , Witkowski Marco , Buffa Jennifer A. , Sun Yu , Li Lin , Menge Christopher M. , Demuth Ilja , König Maximilian , Steinhagen-Thiessen Elisabeth , DiDonato Joseph A. , Deb Arjun , Bäckhed Fredrik , Tang W.H. Wilson , Naga Prasad Sathyamangla Venkata , Landmesser Ulf , Van Wagoner David R. , Hazen Stanley L. 
Published: December 2022

Background:
The gut microbiota-dependent metabolite phenylacetylgutamine (PAGln) is both associated with atherothrombotic heart disease in humans, and mechanistically linked to cardiovascular disease pathogenesis in animal models via modulation of adrenergic receptor signaling.

Methods:
Here we examined both clinical and mechanistic relationships between PAGln and heart failure (HF). First, we examined associations among plasma levels of PAGln and HF, left ventricular ejection fraction, and N-terminal pro-B-type natriuretic peptide in 2 independent clinical cohorts of subjects undergoing coronary angiography in tertiary referral centers (an initial discovery US Cohort, n=3256; and a validation European Cohort, n=829). Then, the impact of PAGln on cardiovascular phenotypes relevant to HF in cultured cardiomyoblasts, and in vivo were also examined.

Results:
Circulating PAGln levels were dose-dependently associated with HF presence and indices of severity (reduced ventricular ejection fraction, elevated N-terminal pro-B-type natriuretic peptide) independent of traditional risk factors and renal function in both cohorts. Beyond these clinical associations, mechanistic studies showed both PAGln and its murine counterpart, phenylacetylglycine, directly fostered HF-relevant phenotypes, including decreased cardiomyocyte sarcomere contraction, and B-type natriuretic peptide gene expression in both cultured cardiomyoblasts and murine atrial tissue.

Conclusions:
The present study reveals the gut microbial metabolite PAGln is clinically and mechanistically linked to HF presence and severity. Modulating the gut microbiome, in general, and PAGln production, in particular, may represent a potential therapeutic target for modulating HF.

Registration:

URL:
https://clinicaltrials.gov/
; Unique identifier: NCT00590200 and URL:
https://drks.de/drks_web/
; Unique identifier: DRKS00020915.
Stages of Valvular Heart Disease Among Older Adults in the Community: The Atherosclerosis Risk in Communities Study
Authors: Shelbaya Khaled , Claggett Brian , Dorbala Pranav , Skali Hicham , Solomon Scott D. , Matsushita Kunihiro , Konety Suma , Mosley Thomas H. , Shah Amil M. 
Published: December 2022

Background:
Limited data exist on American College of Cardiology/American Heart Association valvular heart disease (VHD) stage prevalence, progression, and association with incident cardiovascular diseases in late life.

Methods:
Participants in the ARIC study (Atherosclerosis Risk in Communities), a prospective community-based cohort study, underwent protocol echocardiography at ARIC visits 5 (2011–2013) and 7 (2018–2019), and their aortic stenosis, aortic regurgitation, mitral stenosis, and mitral regurgitation stage were defined according to American College of Cardiology/American Heart Association guidelines. The overall VHD stage prevalence at visit 5 was measured. The associations between VHD stages and incident adjudicated death, heart failure, coronary heart disease, stroke, and atrial fibrillation were assessed with Cox proportional hazard models adjusted for age, sex, race, hypertension, diabetes, prior myocardial infarction, heart failure, body mass index, study center, systolic blood pressure, estimated glomerular filtration rate, and low-density lipoprotein at visit 5. Longitudinal changes in VHD stage prevalence over ≈6 years were estimated with inverse probability of attrition weights to account for participant attrition.

Results:
Among 6118 ARIC participants, the mean±SD age was 76±5 years, 42% were male, and 22% reported Black race. Stage A VHD was present in 39%, stage B in 17%, and stage C/D in 1.1%;, 0.7% had previously undergone valve replacement or repair. A graded association was observed between stage A, B, and C/D VHD and risk of all-cause mortality, incident heart failure, incident atrial fibrillation, and incident coronary heart disease, but not incident stroke. Similar findings were observed for stages of each valvular lesion individually. During the 6.6 years (interquartile range, 6.1–7.0 years) between visits 5 and 7 (mean age, 81±4 years), the prevalence of freedom from VHD stage decreased from 43% to 24%, whereas the prevalence of stage C/D VHD increased from 1% to 7%.

Conclusions:
Subclinical VHD is common in older adults, with 39% at risk (stage A) and 17% with progressive VHD (stage B), and is independently associated with risk of incident cardiovascular events. VHD stages progress over 6 years in late life, with a several-fold increase in prevalence of severe VHD (stage C/D), highlighting the public health importance of interventions to mitigate VHD progression.
Understanding the Rice Fungal Pathogen Tilletia horrida from Multiple Perspectives
Authors: Wang Aijun , Shu Xinyue , Xu Deze , Jiang Yuqi , Liang Juan , Yi Xiaoqun , Zhu Jianqing , Yang Feng , Jiao Chunhai , Zheng Aiping , Yin Desuo , Li Ping 
Published: December 2022

AbstractRice kernel smut (RKS), caused by the fungus Tilletia horrida, has become a major disease in rice-growing areas worldwide, especially since the widespread cultivation of high-yielding hybrid rice varieties. The disease causes a significant yield loss during the production of rice male sterile lines by producing masses of dark powdery teliospores. This review mainly summarizes the pathogenic differentiation, disease cycle, and infection process of the T. horrida, as well as the decoding of the T. horrida genome, functional genomics, and effector identification. We highlight the identification and characterization of virulence-related pathways and effectors of T. horrida, which could foster a better understanding of the rice–T. horrida interaction and help to elucidate its pathogenicity molecular mechanisms. The multiple effective disease control methods for RKS are also discussed, included chemical fungicides, the mining of resistant rice germplasms/genes, and the monitoring and early warning signs of this disease in field settings.
Profiling the BLAST bioinformatics application for load balancing on high-performance computing clusters
Authors: Cheng Trinity , Chin Pei-Ju , Cha Kenny , Petrick Nicholas , Mikailov Mike 
Published: December 2022

Abstract
Background
The Basic Local Alignment Search Tool (BLAST) is a suite of commonly used algorithms for identifying matches between biological sequences. The user supplies a database file and query file of sequences for BLAST to find identical sequences between the two. The typical millions of database and query sequences make BLAST computationally challenging but also well suited for parallelization on high-performance computing clusters. The efficacy of parallelization depends on the data partitioning, where the optimal data partitioning relies on an accurate performance model. In previous studies, a BLAST job was sped up by 27 times by partitioning the database and query among thousands of processor nodes. However, the optimality of the partitioning method was not studied. Unlike BLAST performance models proposed in the literature that usually have problem size and hardware configuration as the only variables, the execution time of a BLAST job is a function of database size, query size, and hardware capability. In this work, the nucleotide BLAST application BLASTN was profiled using three methods: shell-level profiling with the Unix “time” command, code-level profiling with the built-in “profiler” module, and system-level profiling with the Unix “gprof” program. The runtimes were measured for six node types, using six different database files and 15 query files, on a heterogeneous HPC cluster with 500+ nodes. The empirical measurement data were fitted with quadratic functions to develop performance models that were used to guide the data parallelization for BLASTN jobs.

Results
Profiling results showed that BLASTN contains more than 34,500 different functions, but a single function, RunMTBySplitDB, takes 99.12% of the total runtime. Among its 53 child functions, five core functions were identified to make up 92.12% of the overall BLASTN runtime. Based on the performance models, static load balancing algorithms can be applied to the BLASTN input data to minimize the runtime of the longest job on an HPC cluster. Four test cases being run on homogeneous and heterogeneous clusters were tested. Experiment results showed that the runtime can be reduced by 81% on a homogeneous cluster and by 20% on a heterogeneous cluster by re-distributing the workload.

Discussion
Optimal data partitioning can improve BLASTN’s overall runtime 5.4-fold in comparison with dividing the database and query into the same number of fragments. The proposed methodology can be used in the other applications in the BLAST+ suite or any other application as long as source code is available.
NPGREAT: assembly of human subtelomere regions with the use of ultralong nanopore reads and linked-reads
Authors: Adam Eleni , Ranjan Desh , Riethman Harold 
Published: December 2022

Abstract
Background
Human subtelomeric DNA regulates the length and stability of adjacent telomeres that are critical for cellular function, and contains many gene/pseudogene families. Large evolutionarily recent segmental duplications and associated structural variation in human subtelomeres has made complete sequencing and assembly of these regions difficult to impossible for many loci, complicating or precluding a wide range of genetic analyses to investigate their function.

Results
We present a hybrid assembly method, NanoPore Guided REgional Assembly Tool (NPGREAT), which combines Linked-Read data with mapped ultralong nanopore reads spanning subtelomeric segmental duplications to potentially overcome these difficulties. Linked-Read sets of DNA sequences identified by matches with 1-copy subtelomere sequence adjacent to segmental duplications are assembled and extended into the segmental duplication regions using Regional Extension of Assemblies using Linked-Reads (REXTAL). Mapped telomere-containing ultralong nanopore reads are then used to provide contiguity and correct orientation for matching REXTAL sequence contigs as well as identification/correction of any misassemblies. Our method was tested for a subset of representative subtelomeres with ultralong nanopore read coverage in the haploid human cell line CHM13. A 10X Linked-Read dataset from CHM13 was combined with ultralong nanopore reads from the same genome to provide improved subtelomere assemblies. Comparison of Nanopore-only assemblies using SHASTA with our NPGREAT assemblies in the distal-most subtelomere regions showed that NPGREAT produced higher-quality and more complete assemblies than SHASTA alone when these regions had low ultralong nanopore coverage (such as cases where large segmental duplications were immediately adjacent to (TTAGGG) tracts).

Conclusion
In genomic regions with large segmental duplications adjacent to telomeres, NPGREAT offers an alternative economical approach to improving assembly accuracy and coverage using linked-read datasets when more expensive HiFi datasets of 10–20 kb reads are unavailable.
Hydrogen peroxide pretreatment assisted phytoremediation of sodium dodecyl sulfate by Juncus acutus L
Authors: Abeed Amany H. A. , Tammam Suzan A. , El-Mahdy M. T. 
Published: December 2022

Abstract
Background
Sodium Dodecyl Sulfate (SDS) an anionic surfactant pollutant has emerged as a serious hazard to the aquatic and terrestrial environment. Due to physical and chemical methodological difficulties for SDS removal, phytoremediation techniques are efficient alternative strategies to tackle such adversities. Juncus acutus L. (J. acutus) is a pioneer wetland species that has been recently exploited for phytoremediation purposes. To our knowledge, the role of exogenous hydrogen peroxide (H2O2), in improving the phytoextraction of SDS has not been examined yet. In this study, pretreatment foliar spray of H2O2 (15 mM) combined with two levels of SDS (50 and 100 ppm) in water culture was evaluated to remove SDS contamination and add value to the phytoremediation process.

Results
The outcomes revealed that J. acutus has considerable translocation and bioaccumulation abilities for SDS and can be utilized as an appropriate hyperaccumulator in SDS-contaminated sites. However, the involvement of H2O2 extended phytoremediation capacity and successive removal of SDS. H2O2 significantly assisted in increasing SDS remediation via more accumulation in J. acutus tissues by 29.9 and 112.4% and decreasing SDS concentration in culture media by 33.3 and 27.3% at 50 and 100 ppm SDS, respectively. Bioaccumulation factor (BCF) increased by 13.8 and 13.2%, while translocation factor (TCF) positively maximized by 82.4 and 76.2% by H2O2 application at 50 and 100 ppm SDS, respectively. H2O2 pretreatment could drive the decline in biochemical attributes in SDS-affected plants by modulating stress tolerance indices, pigments, water relations, proline content, enzymatic activities, and further, reduced oxidative stress in terms of electrolyte leakage, cellular H2O2, malondialdehyde (MDA) accumulation.

Conclusions
H2O2 could play a potential role in maximizing phytoremediation capacity of SDS by J. acutus in polluted sites.
Clinical characteristics of central nervous system candidiasis due to Candida albicans in children: a single-center experience
Authors: Xiao Haijuan , Miao Yiqing , Liu Linlin , Feng Wenya , Liu Shuping , Guo Lingyun , Guo Xin , Chen Tianming , Hu Bing , Hu Huili , Xu Fang , Han Lianlian , Ren Lili , Li Wei , Liu Gang 
Published: December 2022

Abstract
Background
Central nervous system candidiasis due to Candida albicans (CNSC) in children is easily misdiagnosed and is associated with poor outcomes and a high mortality rate. There is no big data research or systematic review of CNSC.

Methods
Patients diagnosed as CNSC with positive culture results of Candida albicans in Beijing Children’s Hospital affiliated to Capital Medical University from March 2010 to March 2019 were included. Patients receiving immunosuppressive therapy or transplantation, or with malignant tumours were excluded. We analysed the clinical characteristics, follow-up results, drug susceptibility tests and whole-exome sequencing (WES) results.

Results
Thirty-three definitive patients were enrolled, including 22 males and 11 females. Twenty-five patients suffered from CNSC when they were less than 1 year old, and a total of 29 patients had high-risk factors. The main clinical manifestations were fever, convulsions, and positive neurological signs. Twenty-two patients had CNS infections alone, and 11 patients had CNS infections combined with invasive infections involving multiple sites. Twenty-seven cases had a positive CSF and/or blood culture at our hospital. All strains were susceptible to fluconazole, and 2 strains had intermediate susceptibility to voriconazole. As for amphotericin B, all the strains were wild type (WT). WES of 16 patients revealed 2 cases with CARD9 mutations, who suffered from recurrent onychomycosis or thrush before.

Conclusion
CNSC mostly existed in children younger than 1 year old, who all had underlying risk factors. CNSC patients with onset at an older age or with recurrent superficial fungal infections might have primary immunodeficiency.