bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Randomized Double-blind Clinical Trial of Weierkang Pills for the Treatment of Chronic Atrophic Gastritis
Authors: Chen Xueqin , Shen Kai , Deng Yanyong , Mo Jianling , Ni Jingdan , Hendi Maher , Chen Shujie , Wang Lan , Si Jianmin 
Published: January 2022

Background and Goals:
There are currently no standard treatments for chronic atrophic gastritis and traditional Chinese medicine may be effective. This study aims to investigate the efficacy and safety of Weierkang pills in treating chronic atrophic gastritis.

Materials and Methods:
There were 108 patients in our study. They were randomly assigned to 2 groups. In group A, patients received Weierkang pills and patients in group B received folic acid combined with teprenone. Symptoms, endoscopic scores, and biopsy specimens were compared at baseline and 3 months after treatment. Meanwhile, the expressions of vascular endothelial growth factor and trefoil factor 3 (TFF3) in biopsy specimens were also compared.

Results:
Our study showed that the total effective rates of atrophy/intestinal metaplasia in group A reached the same level as group B (51.7% vs. 40.0%, P=0.419). Weierkang significantly improved the total effective rate of atrophy/intestinal metaplasia in gastric angle compared with group B (64.7% vs. 33.3%, P=0.024). Weierkang can significantly lower the total Kyoto risk score (2.6±1.1 vs. 3.3±1.0, P=0.002) and atrophy score (1.4±0.6 vs. 1.8±0.5, P=0.001) after treatment. In addition, Weierkang improves symptoms (1.3±1.3 vs. 2.3±1.8, P=0.003) and epigastric pain (0.2±0.4 vs. 0.5±0.6, P=0.041). The expression of TFF3 in gastric mucosa decreased significantly after treatment with Weierkang (P=0.002).

Conclusions:
Weierkang can improve the endoscopic appearance and pathologic changes of chronic atrophic gastritis patients. Symptoms also improved. TFF3 may be involved the pathophysiology mechanism.
Testing key messages about extending cervical screening intervals
Authors: Marlow Laura , Nemec Martin , Barnes Jessica , Waller Jo 
Published: January 2022

ABSTRACTObjectivesWe tested the impact of different messages about the rationale for extended screening intervals on acceptability of an extension.MethodsWomen in England aged 25-49 years (n=2931) were randomised to read different messages about extending intervals from 3 to 5 years. Outcome measures were general acceptability and six components from the Theoretical Framework of Acceptability (TFA).ResultsThe control group were less likely to find the change acceptable (43%) than the groups who saw additional messages (47-63%). Women who saw messages about interval safety, test accuracy or the speed of cell changes had more positive affective attitudes, higher ethicality beliefs, a better understanding of the reasons for the interval change and were more likely to believe that 5-year intervals would be safe. Being up-to-date with screening and previous abnormal results were associated with finding 5-yearly screening unacceptable.ConclusionsEmphasising the slow development of cell changes following an HPV negative result and the safety of longer intervals, alongside messages about the accuracy of HPV primary screening is important.Practical implicationsCampaigns explaining the rationale for increased screening intervals are likely to improve acceptability. Though some women who feel at increased risk, may remain worried even when the rationale is explained.
3D-imaging reveals conserved cerebrospinal fluid drainage via meningeal lymphatic vasculature in mice and humans
Authors: Jacob Laurent , de Brito Neto Jose , Lenck Stephanie , Corcy Celine , Benbelkacem Farhat , Geraldo Luiz Henrique , Xu Yunling , Thomas Jean-Mickael , El Kamouh Marie-Renee , Potier Marie-Claude , Haik Stephane , Lehericy Stephane , Eichmann Anne , Thomas Jean-Leon 
Published: January 2022

AbstractMeningeal lymphatic vessels (MLVs) contribute to waste product elimination and immune surveillance in brain tissues. MLVs were identified in the dorsal and caudo-basal regions of the dura mater, where they ensure the clearance of cerebrospinal fluid (CSF). Whether MLVs exist in the complex anterior part of the murine and human skull, and how they connect with the glymphatic system and extracranial lymphatic vasculature remained unclear. Here, we generated three-dimensional (3D) maps of MLV drainage by light-sheet fluorescence microscopy (LSFM) imaging of mouse whole-head preparations following fluorescent OVA-A555 tracer injections into the CSF. In humans, we performed real-time magnetic resonance vessel wall imaging (MR-VWI) after systemic gadobutrol injections. We observed a conserved 3D-anatomy of MLVs in mice and humans, and we discovered an extended anterior network around the dural cavernous sinus including multiple capillary beds and exit routes through the foramina of emissary veins. MR-VWI may provide a diagnostic tool for patients with CSF drainage defects and neurological diseases.Short abstractWe established the 3D-anatomy of meningeal lymphatic vasculature and associated CSF drainage by postmortem light-sheet imaging in mice and by real-time magnetic resonance imaging in humans, demonstrating conserved lymphatic circuitries in contact with dural venous sinuses.
Systematic Review and Meta-Analysis: Task-based fMRI Studies in Youths with Irritability
Authors: Lee Ka Shu , Hagan Cheyanne , Hughes Mina , Cotter Grace , Freud Eva McAdam , Kircanski Katharina , Leibenluft Ellen , Brotman Melissa , Tseng Wan-Ling 
Published: January 2022

AbstractObjectiveChildhood irritability, operationalized as disproportionate and frequent temper tantrums and low frustration tolerance relative to peers, is a transdiagnostic symptom across many pediatric disorders. Studies using task-dependent functional magnetic resonance imaging (fMRI) to probe neural dysfunction in irritability have increased. However, an integrated review summarizing the published methods and synthesized fMRI results remains lacking.MethodWe conducted a systematic search using irritability terms and task functional neuroimaging in key databases in March 2021, and identified 30 studies for our systematic review. Sample characteristics and fMRI methods were summarized. A subset of 28 studies met the criteria for extracting coordinate-based data for quantitative meta-analysis. Ten activation-likelihood estimations were performed to examine neural convergence across irritability measures and fMRI task domains.ResultsSystematic review revealed small sample sizes (median = 58, mean age range = 8–16 years) with heterogeneous sample characteristics, irritability measures, tasks, and analytical procedures. Meta-analyses found no evidence for neural activation convergence of irritability across neurocognitive functions related to emotional reactivity, cognitive control, and reward processing, nor within each domain. Sensitivity analyses partialing out variances driven by heterogeneous tasks, irritability measures, stimulus types, and developmental ages all yielded null findings.ConclusionThe lack of neural convergence suggests a need for common, standardized irritability assessments and more homogeneous fMRI tasks. Thoughtfully designed fMRI studies probing commonly defined neurocognitive functions may be more fruitful to elucidate the neural mechanisms of irritability. Open science practices, data mining in large neuroscience databases, and standardized analytical methods promote meaningful collaboration in irritability research.
Single-cell multi-omics of human clonal hematopoiesis reveals that DNMT3A R882 mutations perturb early progenitor states through selective hypomethylation
Authors: Nam Anna S. , Dusaj Neville , Izzo Franco , Murali Rekha , Myers Robert M. , Mouhieddine Tarek , Sotelo Jesus , Benbarche Salima , Waarts Michael , Gaiti Federico , Tahri Sabrin , Levine Ross , Abdel-Wahab Omar , Godley Lucy A. , Chaligne Ronan , Ghobrial Irene , Landau Dan A. 
Published: January 2022

ABSTRACTSomatic mutations in cancer genes have been ubiquitously detected in clonal expansions across healthy human tissue, including in clonal hematopoiesis. However, mutated and wildtype cells are morphologically and phenotypically similar, limiting the ability to link genotypes with cellular phenotypes. To overcome this limitation, we leveraged multi-modality single-cell sequencing, capturing the mutation with transcriptomes and methylomes in stem and progenitors from individuals with DNMT3A R882 mutated clonal hematopoiesis. DNMT3A mutations resulted in myeloid over lymphoid bias, and in expansion of immature myeloid progenitors primed toward megakaryocytic-erythroid fate. We observed dysregulated expression of lineage and leukemia stem cell markers. DNMT3A R882 led to preferential hypomethylation of polycomb repressive complex 2 targets and a specific sequence motif. Notably, the hypomethylation motif is enriched in binding motifs of key hematopoietic transcription factors, serving as a potential mechanistic link between DNMT3A R882 mutations and aberrant transcriptional phenotypes. Thus, single-cell multi-omics pave the road to defining the downstream consequences of mutations that drive human clonal mosaicism.
M-TUBE: a fabrication-free microfluidic device for large-volume bacterial electroporation requiring minimal assembly
Authors: Huang Po-Hsun , Chen Sijie , Shiver Anthony L. , Culver Rebecca Neal , Huang Kerwyn Casey , Buie Cullen R. 
Published: January 2022

AbstractConventional cuvette-based and microfluidics-based bacterial electroporation approaches have distinct advantages, but they are typically limited to relatively small sample volumes, reducing their utility for applications requiring high throughput such as the generation of mutant libraries. Here, we present a disposable, user-friendly microfluidic electroporation device capable of processing large volume bacterial samples yet requiring minimal device fabrication and straightforward operation. We demonstrate that the proposed device can outperform conventional cuvettes in a range of situations, including across Escherichia coli strains with a range of electroporation efficiencies, and we use its large-volume bacterial electroporation capability to generate a library of transposon mutants in the anaerobic gut commensal Bifidobacterium longum.
Rapid transgenerational adaptation in response to intercropping increases facilitation and reduces competition
Authors: Stefan Laura , Engbersen Nadine , Schöb Christian 
Published: January 2022

SummaryBy capitalising on positive biodiversity-productivity relationships, intercropping provides opportunities to improve agricultural sustainability1. However, intercropping is generally implemented using commercial seeds that were bred for maximal productivity in monocultures, which might limit the benefits of crop diversity on yield2,3. Plants can adapt over generations to the level of surrounding plant diversity, notably through increases in niche differentiation4. However, this adaptation potential and the corresponding yield benefit potential have not been explored in annual crop systems. Here we show that plant–plant interactions among annual crops evolved towards increased facilitation and reduced competition when the plants’ coexistence history matched their current diversity setting, which led to an increase in overyielding of up to 58%. These higher yield benefits were linked to character convergence between species sharing the same coexistence history for two generations. Notably, the six crop species tested converged towards taller phenotypes with lower leaf dry matter content when grown in mixtures. This study provides the first empirical evidence for the importance of parental diversity affecting plant–plant interactions and ecosystem functioning of the following generations in annual cropping systems. These results have important implications for diversified agriculture as they demonstrate the yield potential of targeted cultivars for intercropping, which can be achieved through specific breeding for mixtures.
SELINA: Single-cell Assignment using Multiple-Adversarial Domain Adaptation Network with Large-scale References
Authors: Ren Pengfei , Shi Xiaoying , Dong Xin , Yu Zhiguang , Ding Xuanxin , Wang Jin , Sun Liangdong , Yan Yilv , Hu Junjie , Zhang Peng , Chen Qianming , Li Taiwen , Wang Chenfei 
Published: January 2022

AbstractThe rapid accumulation of single-cell RNA-seq data has provided rich resources to characterize various human cell types. Cell type annotation is the critical step in analyzing single-cell RNA-seq data. However, accurate cell type annotation based on public references is challenging due to the inconsistent annotations, batch effects, and poor characterization of rare cell types. Here, we introduce SELINA (single cELl identity NAvigator), an integrative annotation transferring framework for automatic cell type annotation. SELINA optimizes the annotation for minority cell types by synthetic minority over-sampling, removes batch effects among reference datasets using a multiple-adversarial domain adaptation network (MADA), and fits the query data with reference data using an autoencoder. Finally, SELINA affords a comprehensive and uniform reference atlas with 1.7 million cells covering 230 major human cell types. We demonstrated the robustness and superiority of SELINA in most human tissues compared to existing methods. SELINA provided a one-stop solution for human single-cell RNA-seq data annotation with the potential to extend for other species.
Combining LSD1 and JAK-STAT inhibition targets Down syndrome-associated myeloid leukemia at its core
Authors: Grimm Juliane , Bahyadia Raj , Gack Lucie , Heckl Dirk , Klusmann Jan-Henning 
Published: January 2022

AbstractChildren with Down syndrome (DS) are predisposed to developing megakaryoblastic leukemia (ML-DS) and often experience severe toxicities from chemotherapy, highlighting the need for targeted therapies with beneficial risk profiles. The genomic landscape of ML-DS is characterized by a combination of mutations in signaling pathway genes and epigenetic modifiers, while aberrant lysine specific demethylase 1 (LSD1) and JAK-STAT activation have both been implicated in leukemogenesis. Here, we demonstrate that combined LSD1 and JAK1/2 inhibition exerts synergistic anti-leukemic effects specifically in ML-DS, both in vitro and in patient derived xenografts in vivo. The JAK1/2 inhibitor ruxolitinib enhanced the LSD1 inhibitor-induced differentiation, proliferation arrest and apoptosis in patient-derived leukemic blasts. At the transcriptional level, the combination synergistically repressed gene expression signatures essential for cell division. We further observed an immunogenic gene expression pattern in the form of increased cytokine signaling, which – by sensitizing ML-DS blasts to the JAK-STAT signaling blockade induced by ruxolitinib – could explain the increased susceptibility of ML-DS blasts to combination therapy. Taken together, we establish combined LSD1 and JAK-STAT inhibition as an efficacious therapeutic regimen specifically designed to target important steps in ML-DS leukemogenesis, paving the way for targeted therapies in this entity.
Kynurenine metabolism is altered in mdx mice: a potential muscle to brain connection
Authors: Copeland Emily N. , Whitley Kennedy C. , Watson Colton J.F. , Baranowski Bradley J. , Kurgan Nigel , MacNeil Adam J. , MacPherson Rebecca E.K. , Fajardo Val A. , Allison David J. 
Published: January 2022

AbstractRegular exercise can direct muscle kynurenine (KYN) metabolism toward the neuroprotective branch of the kynurenine pathway thereby limiting the accumulation of neurotoxic metabolites in the brain and contributing to mental resilience. While the effect of regular exercise has been studied, the effect of muscle disease on KYN metabolism has not yet been investigated. Previous work has highlighted anxiety-like behaviors in approximately 25% of patients with DMD, possibly due to altered KYN metabolism. Here, we characterized KYN metabolism in mdx mouse models of Duchenne muscular dystrophy (DMD). Young (8-10 week old) DBA/2J (D2) mdx mice, but not age-matched C57BL/10 (C57) mdx mice, had lower levels of circulating KYNA and KYNA:KYN ratio compared with their respective wild-type (WT) controls. Moreover, only D2 mdx mice displayed signs of anxiety-like behaviour, spending more time in the corners of their cages during a novel object recognition test when compared with WT. Along with this, we found that muscles from D2 mdx mice had less peroxisome proliferator-activated receptor-gamma coactivator 1-alpha and kynurenine amino transferase-1 enzyme content as well as elevated expression of inflammatory cytokines compared with WT muscles. Thus, our pilot work shows that KYN metabolism is altered in D2 mdx mice, with a potential contribution from altered muscle health.
Use of object detection in camera trap image identification: assessing a method to rapidly and accurately classify human and animal detections for research and application in recreation ecology
Authors: Fennell Mitchell , Beirne Christopher , Burton A. Cole 
Published: January 2022

AbstractCamera traps are increasingly used to answer complex ecological questions. However, the rapidly growing number of images collected presents technical challenges. Each image must be classified to extract data, requiring significant labour, and potentially creating an information bottleneck. We applied an object-detection model (MegaDetector) to camera trap data from a study of recreation ecology in British Columbia, Canada. We tested its performance in detecting humans and animals relative to manual image classifications, and assessed efficiency by comparing the time required for manual classification versus a modified workflow integrating object-detection with manual classification. We also evaluated the reliability of using MegaDetector to create an index of human activity for application to the study of recreation impacts to wildlife. In our application, MegaDetector detected human and animal images with 99% and 82% precision, and 95% and 92% recall respectively, at a confidence threshold of 90%. The overall time required to process the dataset was reduced by over 500%, and the manual processing component was reduced by 840%. The index of human detection events from MegaDetector matched the output from manual classification, with a mean 0.45% difference in estimated human detections across site-weeks. Our test of an open-source object-detection model showed it performed well in partially classifying a camera trap dataset, significantly increasing processing efficiency. We suggest that this tool could be integrated into existing camera trap workflows to accelerate research and application by alleviating data bottlenecks, particularly for surveys processing large volumes of human images. We also show how the model and workflow can be used to anonymize human images prior to classification, protecting individual privacy.Impact StatementWe developed and tested a workflow for classifying camera trap images that integrated an existing object-detection model with manual image classification. Our workflow demonstrates an increase in efficiency of 500% over manual labelling, and additionally includes a method to anonymize human images prior to archiving and classification. We provide an example of the application of these tools to ease data processing, particularly for studies focused on recreation ecology which record high volumes of human images. Data lags due to processing delays have the potential to result in sub-optimal conservation decisions, which may be alleviated by accelerated processing. To our knowledge, this is the first in-depth assessment of the practical application of such technology to real world workflows focused on human detections.
Clinical Utility of Combined Optical Genome Mapping and 523-gene Next Generation Sequencing Panel For Comprehensive Evaluation of Myeloid Cancers
Authors: Sahajpal Nikhil Shri , Mondal Ashis K , Ananth Sudha , Saul Daniel , Shams Soheil , Hastie Alex R , Savage Natasha M. , Kota Vamsi , Chaubey Alka , Kolhe Ravindra 
Published: January 2022

AbstractThe standard-of-care (SOC) for genomic testing of myeloid cancers primarily relies on karyotyping and fluorescent in situ hydridization (FISH) (cytogenetic analysis) and targeted gene panels (≤54 genes) that harbor hotspot pathogenic variants (molecular genetic analysis). Both cytogenetic and molecular testing workup is necessary for the identification and detection of large structural variants (SVs) and small variants like single nucleotide variants (SNV) and indels, respectively. Despite this combinatorial approach, ∼50% of myeloid cancer genomes remain cytogenetically normal, and the limited sequencing variant profiles obtained from targeted panels are unable to resolve the genetic etiology of these myeloid tumors. In this study, we evaluated the performance and clinical utility of optical genome mapping (OGM) and a 523-gene next-generation sequencing (NGS) panel for comprehensive genomic profiling of 15 myeloid tumors and compared it to SOC cytogenetic methods (karyotyping and FISH) and a 54-gene NGS panel. OGM and the 523-gene NGS panel were found to have an analytical concordance of 100% with karyotyping, FISH, and the 54-gene panel, respectively. Additionally, OGM better characterized and resolved the structural variants previously reported by karyotyping in five cases, such as identifying the genomic content of marker and ring chromosomes. OGM also identified several additional translocations and eleven copy number variations (CNVs), of which the CNVs were validated/confirmed by the 523-gene panel. The 523-gene panel identified seven additional clinically relevant SNVs (two tier 1A variants and five tier 2C variants, as per the ACMG/AMP guidelines) in four cases. The simultaneous visualization of SVs and small NGS detected sequence variants (SNVs and small indels) from OGM and 523-gene NGS panel, respectively in the NxClinical software v6.1 identified two clinically relevant compound heterozygous events in two samples. This study demonstrates the higher sensitivity, resolution, accuracy, and ability to reveal cryptic and clinically relevant novel variants in myeloid cancers as compared to SOC methodologies. Our cost-effective approach of using OGM and a 523-gene NGS panel for comprehensive genomic profiling of myeloid cancers will not only increase the yield of actionable targets leading to improved clinical outcomes but also help resolve our ongoing conundrum of apparently genomically normal myeloid cancers by providing more answers.