bluuebunny/crossref_metadata_2025_split huggingface dataset:
Assessment of the Degree of Osteoarthritis in Aging Male and Female Femoral Condyles: A Cadaveric Study
Authors: Immonen Jessica , Stevens Kelsey , Albin Alexa , Chaus David , Gilmer Lesley , Zdilla Matthew 
Published: May 2020

Objective Determine if femoral chondral cartilage degeneration on cadaveric knee joints exacerbate differently with aging between the sexes. Methods A total of 85 cadaveric femurs were assessed for macroscopic femoral condyle pathology using a scale for gross signs of osteoarthritis. Raters scored specimens and raters’ scores were averaged to provide each specimen a Disease Severity Score (DSS). Results The DSS for the 80+-year-old population was greater than the DSS of the 70- to 79-year-old population (* P < 0.05) and the <70-year-old population (** P < 0.01). Specimens that scored a DSS of 2 and higher were assessed for their specific site of most severe degeneration. The most severe degeneration on the articular cartilage was most regularly on the patellar fossa. The second most degenerated region varied by age and biomechanical alterations. There were no significant changes in DSS between the sexes within the age groups. Conclusions No difference was shown between the sexes in the severity or location of degeneration indicating that men and women are likely affected by the same biomechanical changes that spur on osteoarthritis in their eighth decade of life (70s) and later. Lateral femoral degeneration predominates in younger populations. When patients approach their 70s, medial degeneration begins to predominate likely based on an increase in shearing at the knee joint.
Osteochondral Autograft Plugs versus Paste Graft: Ex Vivo Morselization Increases Chondral Matrix Production
Authors: Grande Daniel , Goldstein Todd , Turek Thomas J. , Hennessy Susan , Walgenbach Ann W. , Do Le Hanh Dung , Greene David , Stone Kevin R. 
Published: May 2020

Objective Patients undergoing articular cartilage paste grafting have been shown in studies to have significant improvement in pain and function in long-term follow-ups. We hypothesized that ex vivo impacting of osteochondral autografts results in higher chondrocyte matrix production versus intact osteochondral autograft plugs. Design This institutional review board–approved study characterizes the effects of impacting osteochondral plugs harvested from the intercondylar notch of 16 patients into a paste, leaving one graft intact as a control. Cell viability/proliferation, collagen type I/II, SOX-9, and aggrecan gene expression via qRT-PCR (quantitative reverse transcription-polymerase chain reaction) were analyzed at 24 and 48 hours. Matrix production and cell morphology were evaluated using histology. Results Paste samples from patients (mean age 39.7) with moderate (19%) to severe (81%) cartilage lesions displayed 34% and 80% greater cell proliferation compared to plugs at 24 and 48 hours post processing, respectively ( P = 0.015 and P = 0.021). qRT-PCR analysis yielded a significant ( P = 0.000) increase of aggrecan, SOX-9, collagen type I and II at both 24 and 48 hours. Histological examination displayed cell division throughout paste samples, with accumulation of aggrecan around multiple chondrocyte lacunae. Conclusions Paste graft preparation resulted in increased mobility of chondrocytes by matrix disruption without loss of cell viability. The impaction procedure stimulated chondrocyte proliferation resulting in a cellular response to reestablish native extracellular matrix. Analysis of gene expression supports a regenerative process of cartilage tissue formation and contradicts long-held beliefs that impaction trauma leads to immediate cell death. This mechanism of action translates into clinical benefit for patients with moderate to severe cartilage damage.
Incorporating hematopoietic stem-cell transplantation after second-line carfilzomib-lenalidomide-dexamethasone (KRd)
Authors: Byun Ja Min , Yoon Sung-Soo , Koh Youngil , Min Chang-Ki , Lee Jae Hoon , Jo Jaemin , Park Hyunkyung , Lee Jiyun , Kang Ka-Won , Lee Yoojin ,   and the Korean Multiple Myeloma Working Party (KMMWP)
Published: May 2020

Background: Traditionally believed to be an integral part of multiple myeloma (MM) treatment, the role of hematopoietic stem-cell transplantation (HSCT) is being challenged. As such, we sought to evaluate the impact of HSCT in the era of novel agents. Methods: A multicenter, retrospective, longitudinal cohort study was carried out between January 2016 and December 2018. A total of 55 patients who received VTD (bortezomib-thalidomide-dexamethasone) as first-line treatment and KRd (carfilzomib-lenalidomide-dexamethasone) as second-line treatment were analyzed for outcomes. Results: The enrolled patients were divided into Group 1, defined as those who continued KRd treatment until progression ( n = 41), versus Group 2, defined as those who underwent HSCT after a certain number of cycles of KRd ( n = 14). Both groups showed a generally favorable response to KRd, with overall response rate (ORR) of 87.9% and clinical benefit rate of 92.8% after a median of seven cycles in Group 1, and ORR 92.8% and clinical benefit rate 100% after median of five cycles in Group 2. However, significantly poorer progression-free survival (PFS) ( p = 0.004) was observed in Group 1 (median 12 months) compared with Group 2 (median not reached). Multivariate analyses identified HSCT after KRd as potential risk factors associated with PFS. Also, in Group 1, bortezomib refractoriness was associated with significantly shorter PFS compared with those who were responsive (median 12 months versus 14 months, respectively, p = 0.039). Conclusions: In conclusion, even with the advent of novel agents, HSCT still remains a valuable treatment modality with additive efficacy.
A 5-year experience characterizing the demographic and clinical profile and directly observed treatment short-course treatment outcome in National Tuberculosis Center of Duhok province, Iraqi Kurdistan
Authors: Merza Muayad Aghali 
Published: May 2020

Background: The objectives were to describe the demographic and clinical profile and treatment outcomes in the National Tuberculosis Program Center of Duhok governorate. Methods: This was a descriptive retrospective study of all forms of drug-susceptible tuberculosis cases in the National Tuberculosis Program Center of Duhok. The Electronic Nominal Recording Reporting System data of tuberculosis cases were reviewed during 2014–2018. Information on the demographic, clinical, and laboratory characteristics of the patients were analyzed. Tuberculosis trends and treatment outcomes were determined. Results: A total of 1063 tuberculosis patients visited the National Tuberculosis Program Center, of whom 905 were from Duhok. The estimated tuberculosis notification rate per 100,000 people in Duhok governorate was 14.06, 16.16, 10.43, 11.05, and 10.34 for the years 2014, 2015, 2016, 2017, and 2018, respectively. The most affected age group was 15–24 years. The male cases were predominant. Most patients (97.3%) were native Iraqi. There were 718 (67.5%) pulmonary tuberculosis cases and 345 (32.5%) extra-pulmonary tuberculosis cases; tuberculosis lymphadenitis was the most common presentation. The majority of extra-pulmonary tuberculosis patients were females aged 15–24 years (p = 0.019), and patients aged ⩾65 years were associated with pulmonary tuberculosis and extra-pulmonary tuberculosis in males (p ⩽ 0.001). The highest tuberculosis incidence occurred in winter (288 patients). The patient treatment outcomes were as follows: 90.7% successful treatment, 1.6% lost to follow-up, 6.7% death, 0.3 transferred out, and 0.8 treatment failure. Conclusion: There was a high frequency of extra-pulmonary tuberculosis, which may reflect overestimation in its diagnosis. Therefore, meticulous evaluations should be provided. The treatment outcome was satisfactory in the center. Hence, we should maintain the favorable work to attain tuberculosis control objectives. Performing GeneXpert for all tuberculosis cases and introducing culture and drug susceptibility testing should be an urgent plan to strengthen the diagnosis of susceptible and drug-resistant tuberculosis cases.
The Association of MRI Findings and Long-Term Disability in Patients With Chronic Low Back Pain
Authors: Udby Peter Muhareb , Ohrt-Nissen Søren , Bendix Tom , Brorson Stig , Carreon Leah Y. , Andersen Mikkel Østerheden 
Published: May 2020

Study Design: Longitudinal cohort study with 13-year follow-up. Objective: To assess whether long-term disability is associated with baseline degenerative magnetic resonance imaging (MRI) findings in patients with low back pain (LBP). Methods: In 2004-2005, patients aged 18 to 60 years with chronic LBP were enrolled in a randomized controlled trial and lumbar MRI was performed. Patients completed the Roland-Morris Disability Questionnaire (RMDQ) and the LBP Rating Scale, at baseline and 13 years after the MRI. Multivariate regression analysis was performed with 13-year RMDQ as the dependent variable and baseline disc degeneration (DD, Pfirrmann grade), Modic changes (MC), facet joint degeneration (FJD, Fujiwara grade) smoking status, body mass index, and self-reported weekly physical activity at leisure as independent variables. Results: Of 204 patients with baseline MRI, 170 (83%) were available for follow-up. Of these, 88 had Pfirrmann grade >III (52%), 67 had MC (39%) and 139 had Fujiwara grade >2 (82%) on at least 1 lumbar level. Only MC (β = −0.15, P = .031) and weekly physical activity at leisure (β = −0.51, P < .001) were significantly, negatively, associated with 13-year RMDQ-score ( R2 = 0.31). Conclusion: DD and FJD were not associated with long-term disability. Baseline MC and weekly physical activity at leisure were statistically significantly associated with less long-term disability.
IKAROS and CK2 regulate expression of BCL-XL and chemosensitivity in high-risk B-cell acute lymphoblastic leukemia
Authors: Song Chunhua , Ge Zheng , Ding Yali , Tan Bi-Hua , Desai Dhimant , Gowda Krishne , Amin Shantu , Gowda Raghavendra , Robertson Gavin P. , Yue Feng , Huang Suming , Spiegelman Vladimir , Payne Jonathon L. , Reeves Mark E. , Gurel Zafer , Iyer Soumya , Dhanyamraju Pavan Kumar , Xiang Meixian , Kawasawa Yuka Imamura , Cury Nathalia M. , Yunes José Andrés , McGrath Mary , Schramm Joe , Su Ruijun , Yang Yiping , Zhao Zhijun , Lyu Xiaoguang , Muschen Markus , Payne Kimberly J. , Gowda Chandrika , Dovat Sinisa 
Published: May 2020

AbstractHigh-risk B-cell acute lymphoblastic leukemia (B-ALL) is an aggressive disease, often characterized by resistance to chemotherapy. A frequent feature of high-risk B-ALL is loss of function of the IKAROS (encoded by the IKZF1 gene) tumor suppressor. Here, we report that IKAROS regulates expression of the BCL2L1 gene (encodes the BCL-XL protein) in human B-ALL. Gain-of-function and loss-of-function experiments demonstrate that IKAROS binds to the BCL2L1 promoter, recruits histone deacetylase HDAC1, and represses BCL2L1 expression via chromatin remodeling. In leukemia, IKAROS’ function is impaired by oncogenic casein kinase II (CK2), which is overexpressed in B-ALL. Phosphorylation by CK2 reduces IKAROS binding and recruitment of HDAC1 to the BCL2L1 promoter. This results in a loss of IKAROS-mediated repression of BCL2L1 and increased expression of BCL-XL. Increased expression of BCL-XL and/or CK2, as well as reduced IKAROS expression, are associated with resistance to doxorubicin treatment. Molecular and pharmacological inhibition of CK2 with a specific inhibitor CX-4945, increases binding of IKAROS to the BCL2L1 promoter and enhances IKAROS-mediated repression of BCL2L1 in B-ALL. Treatment with CX-4945 increases sensitivity to doxorubicin in B-ALL, and reverses resistance to doxorubicin in multidrug-resistant B-ALL. Combination treatment with CX-4945 and doxorubicin show synergistic therapeutic effects in vitro and in preclinical models of high-risk B-ALL. Results reveal a novel signaling network that regulates chemoresistance in leukemia. These data lay the groundwork for clinical testing of a rationally designed, targeted therapy that combines the CK2 inhibitor, CX-4945, with doxorubicin for the treatment of hematopoietic malignancies.
MDH1-mediated malate-aspartate NADH shuttle maintains the activity levels of fetal liver hematopoietic stem cells
Authors: Gu Hao , Chen Chiqi , Hao Xiaoxin , Su Ni , Huang Dan , Zou Yejun , Lin Shu-Hai , Chen Xianjun , Zheng Denghao , Liu Ligen , Yu Zhuo , Xie Li , Zhang Yaping , He Xiaoxiao , Lai Xiaoyun , Zhang Xiaocui , Chen Guo-Qiang , Zhao Yuzheng , Yang Yi , Loscalzo Joseph , Zheng Junke 
Published: May 2020

Abstract
The connections between energy metabolism and stemness of hematopoietic stem cells (HSCs) at different developmental stages remain largely unknown. We generated a transgenic mouse line for the genetically encoded NADH/NAD+ sensor (SoNar) and demonstrate that there are 3 distinct fetal liver hematopoietic cell populations according to the ratios of SoNar fluorescence. SoNar-low cells had an enhanced level of mitochondrial respiration but a glycolytic level similar to that of SoNar-high cells. Interestingly, 10% of SoNar-low cells were enriched for 65% of total immunophenotypic fetal liver HSCs (FL-HSCs) and contained approximately fivefold more functional HSCs than their SoNar-high counterparts. SoNar was able to monitor sensitively the dynamic changes of energy metabolism in HSCs both in vitro and in vivo. Mechanistically, STAT3 transactivated MDH1 to sustain the malate-aspartate NADH shuttle activity and HSC self-renewal and differentiation. We reveal an unexpected metabolic program of FL-HSCs and provide a powerful genetic tool for metabolic studies of HSCs or other types of stem cells.
Developmental trajectory of prehematopoietic stem cell formation from endothelium
Authors: Zhu Qin , Gao Peng , Tober Joanna , Bennett Laura , Chen Changya , Uzun Yasin , Li Yan , Howell Elizabeth D. , Mumau Melanie , Yu Wenbao , He Bing , Speck Nancy A. , Tan Kai 
Published: May 2020

AbstractHematopoietic stem and progenitor cells (HSPCs) in the bone marrow are derived from a small population of hemogenic endothelial (HE) cells located in the major arteries of the mammalian embryo. HE cells undergo an endothelial to hematopoietic cell transition, giving rise to HSPCs that accumulate in intra-arterial clusters (IAC) before colonizing the fetal liver. To examine the cell and molecular transitions between endothelial (E), HE, and IAC cells, and the heterogeneity of HSPCs within IACs, we profiled ∼40 000 cells from the caudal arteries (dorsal aorta, umbilical, vitelline) of 9.5 days post coitus (dpc) to 11.5 dpc mouse embryos by single-cell RNA sequencing and single-cell assay for transposase-accessible chromatin sequencing. We identified a continuous developmental trajectory from E to HE to IAC cells, with identifiable intermediate stages. The intermediate stage most proximal to HE, which we term pre-HE, is characterized by increased accessibility of chromatin enriched for SOX, FOX, GATA, and SMAD motifs. A developmental bottleneck separates pre-HE from HE, with RUNX1 dosage regulating the efficiency of the pre-HE to HE transition. A distal candidate Runx1 enhancer exhibits high chromatin accessibility specifically in pre-HE cells at the bottleneck, but loses accessibility thereafter. Distinct developmental trajectories within IAC cells result in 2 populations of CD45+ HSPCs; an initial wave of lymphomyeloid-biased progenitors, followed by precursors of hematopoietic stem cells (pre-HSCs). This multiomics single-cell atlas significantly expands our understanding of pre-HSC ontogeny.
How should scientists spread interest in, understanding of, and desire to practice, science more widely among the public?
Authors: Leigh Egbert Giles 
Published: May 2020

AbstractThis is a review of Bruce MacFadden’s Broader Impacts of Science on Society. Here, MacFadden suggests how scientists should, and how the National Science Foundation tries to, spread interest in and understanding of science more widely, especially to underserved minorities, and make science-related professions more accessible to and attractive for these minorities.
Moderate inundation stimulates plant community assembly in the drawdown zone of China’s Three Gorges Reservoir
Authors: Chen Zhongli , Yuan Xingzhong , Roß-Nickoll Martina , Hollert Henner , Schäffer Andreas 
Published: May 2020

Abstract
Background
While a dam is constructed to adjust and store water resources, it has negative impacts on biodiversity of the corresponding ecosystems. In particular, the dam regulation induces water-level fluctuations (WLFs), resulting in remarkable effects on the riparian vegetation succession of the drawdown zone ecosystem. These riparian plant responses play important roles in the biodiversity conservation. However, in-depth investigative adequate studies are still lacking. The objective of this study was to assess the community assembly under the anti-seasonal WLFs of China’s Three Gorges Reservoir (TGR). To analyze the WLFs’ impacts on plant community, the drawdown zone of the TGR was divided into four sub-zones (zone I, II, III, and IV) according to the inundation periods. The community biomass, height, total coverage, and species diversity in each sub-zone were surveyed. To detect the response of individual plant to the WLFs, dominant plants of Echinochloa crusgalli, Setaria viridis, Bidens pilosa, and Xanthium sibiricum were selected as targeted species to compare the plant’s morphological and physiological traits between non-flooded area and the moderately inundated area.

Results
The peaks of community biomass (1859.62 ± 663.77 g), total coverage (103.93 ± 11.81%), and diversity indexes were found in zone II that experienced 90 days of inundation. Community height and total coverage were both significantly negatively correlated to the inundated gradients. Generalized linear models and quadratic regression analyses revealed that community biomass, height, and total coverage were strongly related to the inundated gradients, implying that the inundation is the major factor contributing to the variation of the riparian vegetation patterns. The values of morphological traits (plant height and biomass) in the zone II were higher than those in the non-flooded zone, and were significantly positively correlated with physiological traits.

Conclusions
Community structure, diversity, and functional traits analysis indicated that the drawdown zone referencing to the 90-day inundation was suitable for the plant community establishment. Results on plant functional traits suggest the adaption of riparian plants to the TGR hydrological regime. However, further investigative studies with more plant species are necessary to elucidate their adaptation mechanisms.
TAMA: improved metagenomic sequence classification through meta-analysis
Authors: Sim Mikang , Lee Jongin , Lee Daehwan , Kwon Daehong , Kim Jaebum 
Published: May 2020

Abstract
Background
Microorganisms are important occupants of many different environments. Identifying the composition of microbes and estimating their abundance promote understanding of interactions of microbes in environmental samples. To understand their environments more deeply, the composition of microorganisms in environmental samples has been studied using metagenomes, which are the collections of genomes of the microorganisms. Although many tools have been developed for taxonomy analysis based on different algorithms, variability of analysis outputs of existing tools from the same input metagenome datasets is the main obstacle for many researchers in this field.

Results
Here, we present a novel meta-analysis tool for metagenome taxonomy analysis, called TAMA, by intelligently integrating outputs from three different taxonomy analysis tools. Using an integrated reference database, TAMA performs taxonomy assignment for input metagenome reads based on a meta-score by integrating scores of taxonomy assignment from different taxonomy classification tools. TAMA outperformed existing tools when evaluated using various benchmark datasets. It was also successfully applied to obtain relative species abundance profiles and difference in composition of microorganisms in two types of cheese metagenome and human gut metagenome.

Conclusion
TAMA can be easily installed and used for metagenome read classification and the prediction of relative species abundance from multiple numbers and types of metagenome read samples. TAMA can be used to more accurately uncover the composition of microorganisms in metagenome samples collected from various environments, especially when the use of a single taxonomy analysis tool is unreliable. TAMA is an open source tool, and can be downloaded at https://github.com/jkimlab/TAMA.
ICGEC: a comparative method for measuring epigenetic conservation of genes via the integrated signal from multiple histone modifications between cell types
Authors: Tang Jing , Wu Zefeng , Tian Yuhan , Yang Ruolin 
Published: May 2020

Abstract
Background
Histone post-translational modifications play crucial roles in epigenetic regulation of gene expression and are known to be associated with the phenotypic differences of different cell types. Therefore, it is of fundamental importance to dissect the genes and pathways involved in such a phenotypic variation at the level of epigenetics. However, the existing comparative approaches are largely based on the differences, especially the absolute difference in the levels of individual histone modifications of genes under contrasting conditions. Thus, a method for measuring the overall change in the epigenetic circumstance of each gene underpinned by multiple types of histone modifications between cell types is lacking.

Results
To address this challenge, we developed ICGEC, a new method for estimating the degree of epigenetic conservation of genes between two cell lines. Different from existing comparative methods, ICGEC provides a reliable score for measuring the relative change in the epigenetic context of corresponding gene between two conditions and simultaneously produces a score for each histone mark. The application of ICGEC to the human embryonic stem cell line H1 and four H1-derived cell lines with available epigenomic data for the same 16 types of histone modifications indicated high robustness and reliability of ICGEC. Furthermore, the analysis of the epigenetically dynamic and conserved genes which were defined based on the ICGEC output results demonstrated that ICGEC can deepen our understanding of the biological processes of cell differentiation to overcome the limitations of traditional expression analysis. Specifically, the ICGEC-derived differentiation-direction-specific genes were shown to have putative functions that are well-matched with cell identity. Additionally, H3K79me1 and H3K27ac were found to be the main histone marks accounting for whether an epigenetically dynamic gene was differentially expressed between two cell lines.

Conclusions
The use of ICGEC creates a convenient and robust way to measure the overall epigenetic conservation of individual genes and marks between two conditions. Thus, it provides a basis for exploring the epigenotype-phenotype relationship. ICGEC can be deemed a state-of-the-art method tailored for comparative epigenomic analysis of changes in cell dynamics.