bluuebunny/crossref_metadata_2025_split huggingface dataset:
Single-cell transcriptomics reveals the role of Macrophage-Naïve CD4 + T cell interaction in the immunosuppressive microenvironment of primary liver carcinoma
Authors: Mo Zhuomao , Liu Daiyuan , Chen Yihan , Luo Jin , Li Wenjing , Liu Jiahui , Yu Ling , Huang Bijun , Zhang Shijun 
Published: October 2022

Abstract
Background
Liver carcinoma generally presents as an immunosuppressive microenvironment that promotes tumor evasion. The intercellular crosstalk of immune cells significantly influences the construction of an immunosuppressive microenvironment. This study aimed to investigate the important interactions between immune cells and their targeting drugs in liver carcinoma, by using single-cell and bulk transcriptomic data.

Methods
Single-cell and bulk transcriptomic data were retrieved from Gene Expression Omnibus (GSE159977, GSE136103, and GSE125449) and The Cancer Genome Atlas (TGCA-LIHC), respectively. Quality control, dimension reduction, clustering, and annotation were performed according to the Scanpy workflow based on Python. Cell–cell interactions were explored using the CellPhone database and CellChat. Trajectory analysis was executed using a partition-based graph abstraction method. The transcriptomic factors (TFs) were predicted using single-cell regulatory network inference and clustering (SCENIC). The target genes from TFs were used to establish a related score based on the TCGA cohort; this score was subsequently validated by survival, gene set enrichment, and immune cell infiltration analyses. Drug prediction was performed based on the Cancer Therapeutics Response Portal and PRISM Repurposing datasets.

Results
Thirty-one patients at four different states, including health, hepatitis, cirrhosis, and cancer, were enrolled in this study. After dimension reduction and clustering, twenty-two clusters were identified. Cell–cell interaction analyses indicated that macrophage-naive CD4 + T cell interaction significantly affect cancerous state. In brief, macrophages interact with naive CD4 + T cells via different pathways in different states. The results of SCENIC indicated that macrophages present in cancer cells were similar to those present during cirrhosis. A macrophage-naive CD4 + T cell (MNT) score was generated by the SCENIC-derived target genes. Based on the MNT score, five relevant drugs (inhibitor of polo-like kinase 1, inhibitor of kinesin family member 11, dabrafenib, ispinesib, and epothilone-b) were predicted.

Conclusions
This study reveals the crucial role of macrophage-naive CD4 + T cell interaction in the immunosuppressive microenvironment of liver carcinoma. Tumor-associated macrophages may be derived from cirrhosis and can initiate liver carcinoma. Predictive drugs that target the macrophage-naive CD4 + T cell interaction may help to improve the immunosuppressive microenvironment and prevent immune evasion. The relevant mechanisms need to be further validated in experiments and cohort studies.

Graphical Abstract
The efficacy of azithromycin to prevent exacerbation of non-cystic fibrosis bronchiectasis: a meta-analysis of randomized controlled studies
Authors: Li Kui , Liu Li , Ou Yan 
Published: October 2022

AbstractIntroductionThe efficacy of azithromycin to prevent exacerbation for non-cystic fibrosis bronchiectasis remains controversial. We conduct this meta-analysis to explore the influence of azithromycin versus placebo for the treatment of non-cystic fibrosis bronchiectasis.MethodsWe have searched PubMed, EMbase, Web of science, EBSCO, and Cochrane library databases through July 2019 for randomized controlled trials (RCTs) assessing the efficacy of azithromycin versus placebo for non-cystic fibrosis bronchiectasis. This meta-analysis was performed using the random-effect model.ResultsFour RCTs were included in the meta-analysis. Overall, compared with control group for non-cystic-fibrosis bronchiectasis, azithromycin treatment was associated with improved free of exacerbation (odd ratios [OR] = 3.66; 95% confidence interval [CI] = 1.69–7.93;P = 0.001), reduced pulmonary exacerbations (OR = 0.27; 95% CI 0.13–0.59;P = 0.001) and number of pulmonary exacerbations (standard mean difference [SMD] =  − 0.87; 95% CI − 1.21 to − 0.54;P < 0.00001), but demonstrate no obvious impact on forced expiratory volume in 1 s (FEV1), score on St George’s respiratory questionnaire, nausea or vomiting, adverse events.ConclusionsAzithromycin is effective to prevent exacerbation of non-cystic fibrosis bronchiectasis.
Long-term methylphenidate use for children and adolescents with attention deficit hyperactivity disorder and risk for depression, conduct disorder, and psychotic disorder: a nationwide longitudinal cohort study in South Korea
Authors: Park Jimyung , Lee Dong Yun , Kim Chungsoo , Lee Yo Han , Yang Su-Jin , Lee Sangha , Kim Seong-Ju , Lee Jeewon , Park Rae Woong , Shin Yunmi 
Published: October 2022

Abstract
Background
Methylphenidate (MPH) is the most frequently prescribed medication for the treatment of attention deficit hyperactivity disorder (ADHD). However, the safety of its long-term use remain unclear. In particular, real-world evidence of long-term MPH treatment regarding the risk of depression, conduct disorders, and psychotic disorders in children and adolescents is needed. This study aimed to compare the risks of depression, conduct disorder, and psychotic disorder between long- and short-term MPH treatments in children and adolescents.

Methods
This population-based cohort study used a nationwide claims database of all patients with ADHD in South Korea. Patients aged less than 18 years who were prescribed MPH were included in the study. Long- and short-term MPH were defined as > 1 year, and < 1 year, respectively. Overall, the risk of developing depressive disorder, conduct disorder and oppositional defiant disorder (ODD), and psychotic disorder were investigated. A 1:2 propensity score matching was used to balance the cohorts, and the Cox proportional hazards model was used to evaluate the safety of MPH.

Results
We identified 1309 long-term and 2199 short-term MPH users. Long-term MPH use was associated with a significantly lower risk of depressive (hazard ratio [HR], 0.70 [95% confidence interval [CI] 0.55–0.88]) and conduct disorders and ODD (HR, 0.52 [95% CI 0.38–0.73]) than short-term MPH use. Psychotic disorder was not significantly associated with long-term MPH use (hazard ratio [HR], 0.83 [95% confidence interval [CI] 0.52–1.32]).

Conclusions
Our findings suggest that long-term MPH use may be associated with a decreased risk of depression, conduct disorders and ODD. Moreover, the long-term use of MPH does not increase the risk of psychotic disorders. Long-term MPH administration may be considered as a favourable treatment strategy for children and adolescents with ADHD regarding depressive, conduct, and psychotic disorders.
Quantitative imaging of magnetic nanoparticles in an unshielded environment using a large AC susceptibility array
Authors: Soares Guilherme , Pinto Leonardo , Liebl Maik , Biasotti Gabriel , Prospero Andre , Stoppa Erick , Bakuzis Andris , Baffa Oswaldo , Wiekhorst Frank , Miranda José Ricardo Arruda 
Published: October 2022

Abstract
Background
Non-invasive magnetic imaging techniques are necessary to assist magnetic nanoparticles in biomedical applications, mainly detecting their distribution inside the body. In Alternating Current Biosusceptometry (ACB), the magnetic nanoparticle's magnetization response under an oscillating magnetic field, which is applied through an excitation coil, is detected with a balanced detection coil system.

Results
We built a Multi-Channel ACB system (MC-ACB) containing nineteen pick-up coils and obtained 2D quantitative images of magnetic nanoparticle distributions by solving an inverse problem. We reconstructed the magnetic nanoparticles spatial distributions in a field of view of 14 × 14 cm2 with a spatial resolution of 2.0 cm and sensitivity in the milligram scale. A correlation coefficient between quantitative reconstructed and nominal magnetic nanoparticle distributions above 0.6 was found for all measurements.

Conclusion
Besides other interesting features such as sufficient large field of view dimension for mice and rat studies, portability, and the ability to assess the quantitative magnetic nanoparticles distributions in real-time, the MC-ACB system is a promising tool for quantitative imaging of magnetic nanoparticles distributions in real-time, offering an affordable setup for easy access in clinical or laboratory environments.
The world’s first digital cell twin in cancer electrophysiology: a digital revolution in cancer research?
Authors: Baumgartner Christian 
Published: October 2022

Abstract
Background
The introduction of functional in-silico models, in addition to in-vivo tumor models, opens up new and unlimited possibilities in cancer research and drug development. The world's first digital twin of the A549 cell's electrophysiology in the human lung adenocarcinoma, unveiled in 2021, enables the investigation and evaluation of new research hypotheses about modulating the function of ion channels in the cell membrane, which are important for better understanding cancer development and progression, as well as for developing new drugs and predicting treatments.

Main body
The developed A549 in-silico model allows virtual simulations of the cell’s rhythmic oscillation of the membrane potential, which can trigger the transition between cell cycle phases. It is able to predict the promotion or interruption of cell cycle progression provoked by targeted activation and inactivation of ion channels, resulting in abnormal hyper- or depolarization of the membrane potential, a potential key signal for the known cancer hallmarks. For example, model simulations of blockade of transient receptor potential cation channels (TRPC6), which are highly expressed during S-G2/M transition, result in a strong hyperpolarization of the cell’s membrane potential that can suppress or bypass the depolarization required for the S-G2/M transition, allowing for possible cell cycle arrest and inhibition of mitosis. All simulated research hypotheses could be verified by experimental studies.

Short conclusion
Functional, non-phenomenological digital twins, ranging from single cells to cell–cell interactions to 3D tissue models, open new avenues for modern cancer research through "dry lab" approaches that optimally complement established in-vivo and in-vitro methods.
A PMM2-CDG caused by an A108V mutation associated with a heterozygous 70 kilobases deletion case report
Authors: Lebredonchel E. , Riquet A. , Neut D. , Broly F. , Matthijs G. , Klein A. , Foulquier F. 
Published: October 2022

Abstract
Background
Congenital Disorders of Glycosylation (CDG) are a large group of inborn errors of metabolism with more than 140 different CDG types reported to date (1). The first characterized, PMM2-CDG, with an autosomal recessive transmission, is also the most frequent. The PMM2 gene encodes a phosphomannomutase. Here, a novel genetic variation causing PMM2-CDG is reported.

Case presentation
We report the case of a French child, from healthy and unrelated parents, presenting congenital ataxia with hypotonia, hyperlaxity, inverted nipples, as well as altered coagulation parameters and liver function. Transferrin isoelectrofocusing revealed a typical type I CDG profile. Direct Sanger sequencing and quantitative PCR of PMM2 revealed a unique and novel genotype. On one allele, the patient was heterozygote with a known missense variant NM_000303.3(PMM2):c.323C > T, p.Ala108Val in exon 4. On the second allele, whole genome sequencing (WGS) indicated the presence of a novel heterozygous 70 kb deletion.

Conclusion
We report in the present paper the largest known heterozygous deletion of a PMM2 gene. The observation reveals the impact of a precise diagnostic on genetic counselling: by using WGS, an erroneous conclusion of homozygosity in the case of a relatively rare variant could be avoided, and an index patient with healthy and unrelated parents correctly identified.
PCA outperforms popular hidden variable inference methods for molecular QTL mapping
Authors: Zhou Heather J. , Li Lei , Li Yumei , Li Wei , Li Jingyi Jessica 
Published: October 2022

AbstractBackgroundEstimating and accounting for hidden variables is widely practiced as an important step in molecular quantitative trait locus (molecular QTL, henceforth “QTL”) analysis for improving the power of QTL identification. However, few benchmark studies have been performed to evaluate the efficacy of the various methods developed for this purpose.ResultsHere we benchmark popular hidden variable inference methods including surrogate variable analysis (SVA), probabilistic estimation of expression residuals (PEER), and hidden covariates with prior (HCP) against principal component analysis (PCA)—a well-established dimension reduction and factor discovery method—via 362 synthetic and 110 real data sets. We show that PCA not only underlies the statistical methodology behind the popular methods but is also orders of magnitude faster, better-performing, and much easier to interpret and use.ConclusionsTo help researchers use PCA in their QTL analysis, we provide an R package along with a detailed guide, both of which are freely available athttps://github.com/heatherjzhou/PCAForQTL. We believe that using PCA rather than SVA, PEER, or HCP will substantially improve and simplify hidden variable inference in QTL mapping as well as increase the transparency and reproducibility of QTL research.
Serum total TDP-43 levels are decreased in frontotemporal dementia patients with C9orf72 repeat expansion or concomitant motoneuron disease phenotype
Authors: Katisko Kasper , Huber Nadine , Kokkola Tarja , Hartikainen Päivi , Krüger Johanna , Heikkinen Anna-Leena , Paananen Veera , Leinonen Ville , Korhonen Ville E. , Helisalmi Seppo , Herukka Sanna-Kaisa , Cantoni Valentina , Gadola Yasmine , Archetti Silvana , Remes Anne M. , Haapasalo Annakaisa , Borroni Barbara , Solje Eino 
Published: October 2022

Abstract
Background
Frontotemporal dementia (FTD) covers a spectrum of neurodegenerative disorders with various clinical and neuropathological subtypes. The two major pathological proteins accumulating in the brains of FTD patients, depending on their genetic background, are TDP-43 and tau. We aimed to evaluate whether total TDP-43 levels measured from the serum associate with the genotype or clinical phenotype of the FTD patients and whether serum TDP-43 provides prognostic or diagnostic value in the FTD spectrum disorders.

Methods
The study cohort included 254 participants with a clinical diagnosis of FTD (including all major genotypes and clinical phenotypes) and 105 cognitively healthy controls. Serum total TDP-43 levels measured with a single-molecule array (Simoa) were compared within the FTD group according to the genotype, clinical phenotype, and predicted neuropathological subtype of the patients. We also evaluated the associations between the TDP-43 levels and disease severity or survival in FTD.

Results
Total TDP-43 levels in the serum were significantly lower in the FTD group as compared to the healthy control group (275.3 pg/mL vs. 361.8 pg/mL, B = 0.181, 95%CI = 0.014–0.348, p = 0.034). The lowest TDP-43 levels were observed in the subgroup of FTD patients harboring predicted TDP-43 brain pathology (FTD-TDP, 241.4 pg/mL). The low levels in the FTD-TDP group were especially driven by C9orf72 repeat expansion carriers (169.2 pg/mL) and FTD patients with concomitant motoneuron disease (FTD-MND, 113.3 pg/mL), whereas GRN mutation carriers did not show decreased TDP-43 levels (328.6 pg/mL). Serum TDP-43 levels showed no correlation with disease severity nor progression in FTD.

Conclusions
Our results indicate that the total levels of TDP-43 in the serum are decreased especially in FTD patients with the C9orf72 repeat expansion or FTD-MND phenotype, both subtypes strongly associated with TDP-43 type B brain pathology. Serum-based measurement of TDP-43 could represent a useful tool in indicating C9orf72 repeat expansion and FTD-MND-related TDP-43 neuropathology for future diagnostics and intervention studies.
High visceral adipose tissue area is independently associated with early allograft dysfunction in liver transplantation recipients: a propensity score analysis
Authors: Yuan Guanjie , Li Shichao , Liang Ping , Chen Gen , Luo Yan , Shen Yaqi , Hu Xuemei , Hu Daoyu , Li Jiali , Li Zhen 
Published: October 2022

Abstract
Objectives
To evaluate the association between adipose tissue distribution and early allograft dysfunction (EAD) in liver transplantation (LT) recipients.

Methods
A total of 175 patients who received LT from April 2015 to September 2020 were enrolled in this retrospective study. The areas of abdominal adipose tissue and skeletal muscle of all patients were measured based on the preoperative CT images. The appropriate statistical methods including the propensity score-matched (PSM) analysis were performed to identify the association between adipose tissue distribution and EAD.

Results
Of 175 LT recipients, 55 patients (31.4%) finally developed EAD. The multivariate logistic analysis revealed that preoperative serum albumin (odds ratio (OR) 0.34, 95% confidence interval (CI) 0.17–0.70), platelet–lymphocyte ratio (OR 2.35, 95% CI 1.18–4.79), and visceral adipose tissue (VAT) area (OR 3.17, 95% CI 1.56–6.43) were independent associated with EAD. After PSM analysis, VAT area was still significantly associated with EAD (OR 3.95, 95% CI 1.16–13.51). In survival analysis, no significant difference was identified in one-year graft failure (log-rank: p = 0.487), and conversely result was identified in overall survival (OS) (log-rank: p = 0.012; hazard ratio (HR) 4.10, 95% CI 1.27–13.16).

Conclusions
LT recipients with high VAT area have higher risk for the occurrence of EAD, and high VAT area might have certain clinical value for predicting the poor OS of patients. For LT candidates with large amount of VAT, the clinicians can take clinical interventions by suggesting physical and nutritional treatments to improve outcomes after LT.
Construction of a transposase accessible chromatin landscape reveals chromatin state of repeat elements and potential causal variant for complex traits in pigs
Authors: Jiang Tao , Ling Ziqi , Zhou Zhimin , Chen Xiaoyun , Chen Liqing , Liu Sha , Sun Yingchun , Yang Jiawen , Yang Bin , Huang Jianzhen , Huang Lusheng 
Published: October 2022

Abstract
Background
A comprehensive landscape of chromatin states for multiple mammalian tissues is essential for elucidating the molecular mechanism underlying regulatory variants on complex traits. However, the genome-wide chromatin accessibility has been only reported in limited tissue types in pigs.

Results
Here we report a genome-wide landscape of chromatin accessibility of 20 tissues in two female pigs at ages of 6 months using ATAC-seq, and identified 557,273 merged peaks, which greatly expanded the pig regulatory element repository. We revealed tissue-specific regulatory elements which were associated with tissue-relevant biological functions. We identified both positive and negative significant correlations between the regulatory elements and gene transcripts, which showed distinct distributions in terms of their strength and distances from corresponding genes. We investigated the presence of transposable elements (TEs) in open chromatin regions across all tissues, these included identifications of porcine endogenous retroviruses (PERVs) exhibiting high accessibility in liver and homology of porcine specific virus sequences to universally accessible transposable elements. Furthermore, we prioritized a potential causal variant for polyunsaturated fatty acid in the muscle.

Conclusions
Our data provides a novel multi-tissues accessible chromatin landscape that serve as an important resource for interpreting regulatory sequences in tissue-specific and conserved biological functions, as well as regulatory variants of loci associated with complex traits in pigs.
A novel germline mutation of TP53 with breast cancer diagnosed as Li–Fraumeni syndrome
Authors: Kai Masaya , Kubo Makoto , Shikada Sawako , Hayashi Saori , Morisaki Takafumi , Yamada Mai , Takao Yuka , Shimazaki Akiko , Harada Yurina , Kaneshiro Kazuhisa , Mizuuchi Yusuke , Shindo Koji , Nakamura Masafumi 
Published: October 2022

AbstractTP53 is a tumor suppressor gene and, when dysfunctional, it is known to be involved in the development of cancers. Li–Fraumeni syndrome (LFS) is a hereditary tumor with autosomal dominant inheritance that develops in people with germline pathogenic variants of TP53. LFS frequently develops in parallel to tumors, including breast cancer. We describe a novel germline mutation in TP53 identified by performing a multi-gene panel assay in a breast cancer patient with bilateral breast cancer.
Functionally-explicit sampling can answer key questions about the specificity of plant–microbe interactions
Authors: Fleishman Suzanne M. , Eissenstat David M. , Bell Terrence H. , Centinari Michela 
Published: October 2022

AbstractThe rhizosphere is a nexus for plant–microbe interactions and, as a host-structured environment, a location of high activity for distinct microbes and plant species. Although our insights into this habitat have exploded in recent years, we are still limited in our ability to answer key questions about the specificity of these root-microbial relationships. In particular, it can be difficult to confirm or reject microbiome heritability in many plant systems and to pinpoint which microbial taxa are key to plant functioning. Like other host-structured environments, the rhizosphere is structurally, chemically, and biologically complex, driven largely by differences in root anatomy, location, and function. In this Correspondence, we describe a review of 377 “rhizosphere microbiome” research papers and demonstrate how matching a sampling method to the biological question can advance our understanding of host-microbe interactions in a functionally heterogeneous environment. We found that the vast majority of studies (92%) pool all roots from a root system during sampling, ignoring variation in microbial composition between roots of different function and limiting insight into key root-microbial relationships. Furthermore, approaches for removing root-associated microbes are highly variable and non-standard, complicating multi-study analyses. Our understanding of the strength and nature of host-microbe relationships in heterogenous host-microbiome environments can be clarified by targeting sampling to locations of high interaction. While the high complexity of the rhizosphere creates logistical challenges, we suggest that unambiguous language and refined approaches will improve our ability to match methods to research questions and advance our understanding of the specificity of plant-microbial interactions.