bluuebunny/crossref_metadata_2025_split huggingface dataset:
Long-term persistence of supernumerary B chromosomes in multiple species of Astyanax fish
Authors: Silva Duílio Mazzoni Zerbinato de Andrade , Ruiz-Ruano Francisco J. , Utsunomia Ricardo , Martín-Peciña María , Castro Jonathan Pena , Freire Paula Paccielli , Carvalho Robson Francisco , Hashimoto Diogo T. , Suh Alexander , Oliveira Claudio , Porto-Foresti Fábio , Artoni Roberto Ferreira , Foresti Fausto , Camacho Juan Pedro M. 
Published: March 2021

Abstract
Background
Eukaryote genomes frequently harbor supernumerary B chromosomes in addition to the “standard” A chromosome set. B chromosomes are thought to arise as byproducts of genome rearrangements and have mostly been considered intraspecific oddities. However, their evolutionary transcendence beyond species level has remained untested.

Results
Here we reveal that the large metacentric B chromosomes reported in several fish species of the genus Astyanax arose in a common ancestor at least 4 million years ago. We generated transcriptomes of A. scabripinnis and A. paranae 0B and 1B individuals and used these assemblies as a reference for mapping all gDNA and RNA libraries to quantify coverage differences between B-lacking and B-carrying genomes. We show that the B chromosomes of A. scabripinnis and A. paranae share 19 protein-coding genes, of which 14 and 11 were also present in the B chromosomes of A. bockmanni and A. fasciatus, respectively. Our search for B-specific single-nucleotide polymorphisms (SNPs) identified the presence of B-derived transcripts in B-carrying ovaries, 80% of which belonged to nobox, a gene involved in oogenesis regulation. Importantly, the B chromosome nobox paralog is expressed > 30× more than the A chromosome paralog. This indicates that the normal regulation of this gene is altered in B-carrying females, which could potentially facilitate B inheritance at higher rates than Mendelian law prediction.

Conclusions
Taken together, our results demonstrate the long-term survival of B chromosomes despite their lack of regular pairing and segregation during meiosis and that they can endure episodes of population divergence leading to species formation.
In-silico performance, validation, and modeling of the Nanostring Banff Human Organ transplant gene panel using archival data from human kidney transplants
Authors: Smith R. N. 
Published: March 2021

Abstract
Background
RNA gene expression of renal transplantation biopsies is commonly used to identify the immunological patterns of graft rejection. Mostly done with microarrays, seminal findings defined the patterns of gene sets associated with rejection and non-rejection kidney allograft diagnoses. To make gene expression more accessible, the Molecular Diagnostics Working Group of the Banff Foundation for Allograft Pathology and NanoString Technologies partnered to create the Banff Human Organ Transplant Panel (BHOT), a gene panel set of 770 genes as a surrogate for microarrays (~ 50,000 genes). The advantage of this platform is that gene expressions are quantifiable on formalin fixed and paraffin embedded archival tissue samples, making gene expression analyses more accessible. The purpose of this report is to test in silico the utility of the BHOT panel as a surrogate for microarrays on archival microarray data and test the performance of the modelled BHOT data.

Methods
BHOT genes as a subset of genes from downloaded archival public microarray data on human renal allograft gene expression were analyzed and modelled by a variety of statistical methods.

Results
Three methods of parsing genes verify that the BHOT panel readily identifies renal rejection and non-rejection diagnoses using in silico statistical analyses of seminal archival databases. Multiple modelling algorithms show a highly variable pattern of misclassifications per sample, either between differently constructed principal components or between modelling algorithms. The misclassifications are related to the gene expression heterogeneity within a given diagnosis because clustering the data into 9 groups modelled with fewer misclassifications.

Conclusion
This report supports using the Banff Human Organ Transplant Panel for gene expression of human renal allografts as a surrogate for microarrays on archival tissue. The data modelled satisfactorily with aggregate diagnoses although with limited per sample accuracy and, thereby, reflects and confirms the modelling complexity and the challenges of modelling gene expression as previously reported.
Inequalities in cognitive impairment among older adults in China and the associated social determinants: a decomposition approach
Authors: Deng Qingwen , Liu Wenbin 
Published: March 2021

AbstractBackgroundDespite there is growing evidence focusing on health inequalities in China, socioeconomic inequalities in cognitive impairment among older adults have received little attention. This study aims to measure socioeconomic inequalities in cognitive impairment among Chinese older adults, and determine the contributing social factors to the inequalities.MethodsA cross-sectional analysis was performed using data from the 2018 Chinese Longitudinal Healthy Longevity Survey (CLHLS). A total of 10,556 older adults aged 65 and over were included in the study. The prevalence of cognitive impairment was measured by using the Chinese version of the Mini-Mental State Examination. The socioeconomic inequalities in cognitive impairment were illustrated and quantified by the concentration curve and normalized concentration index. Multivariate logistic regression was conducted to identify the associated factors of cognitive impairment. And decomposition analysis was further applied to decompose the contribution of each determinant to the observed inequalities in cognitive impairment.ResultsThe study indicated that the prevalence of cognitive impairment among Chinese older adults was 18.95%. The overall concentration index for cognitive impairment was − 0.046, which suggested a higher concentration of cognitive impairment among socioeconomically disadvantaged older adults. The results showed the prevalence of cognitive impairment was associated with sex, age, marital status, education level, occupation, economic status, emotional support, financial support, living arrangement, and participation in informal activities. Decomposition results further revealed the contributions of the determinants to the inequalities in cognitive impairment. Specifically, age (131.61%), marital status (85.68%), emotional support (84.85%), education level (39.73%), occupation (21.24%), sex (17.25%), financial support (− 4.19%), economic status (1.02%), living arrangement (0.88%), and informal activities (0.30%) have varying degrees of contributions to the inequality in cognitive impairment.ConclusionThis study sheds light on the pro-rich inequality in cognitive impairment among older adults in China. It suggests that policymakers should pay more attention to older adults who are female, old-old, widowed, illiterate, economically disadvantaged, with no social support, and less socially involved. Also, more targeted interventions should be undertaken to improve the socioeconomic conditions of these vulnerable individuals and strengthen their ability to cope with the risk of cognitive impairment.
A DM1-doped porous gold nanoshell system for NIR accelerated redox-responsive release and triple modal imaging guided photothermal synergistic chemotherapy
Authors: Xu Pengcheng , Wang Ru , Yang Wenqian , Liu Yanyan , He Dongsheng , Ye Zixuan , Chen Daquan , Ding Yuan , Tu Jiasheng , Shen Yan 
Published: March 2021

Abstract
Background
Although many treatments for breast cancer are available, poor tumour targeting limits the effectiveness of most approaches. Consequently, it is difficult to achieve satisfactory results with monotherapies. The lack of accurate diagnostic and monitoring methods also limit the benefits of cancer treatment. The aim of this study was to design a nanocarrier comprising porous gold nanoshells (PGNSs) co-decorated with methoxy polyethylene glycol (mPEG) and trastuzumab (Herceptin®, HER), a therapeutic monoclonal antibody that binds specifically to human epidermal receptor-2 (HER2)-overexpressing breast cancer cells. Furthermore, a derivative of the microtubule-targeting drug maytansine (DM1) was incorporated in the PGNSs.

Methods
Prepared PGNSs were coated with mPEG, DM1 and HER via electrostatic interactions and Au–S bonds to yield DM1-mPEG/HER-PGNSs. SK-BR-3 (high HER2 expression) and MCF-7 (low HER2) breast cancer cells were treated with DM1-mPEG/HER-PGNSs, and cytotoxicity was evaluated in terms of cell viability and apoptosis. The selective uptake of the coated PGNSs by cancer cells and subsequent intracellular accumulation were studied in vitro and in vivo using inductively coupled plasma mass spectrometry and fluorescence imaging. The multimodal imaging feasibility and synergistic chemo-photothermal therapeutic efficacy of the DM1-mPEG/HER-PGNSs were investigated in breast cancer tumour-bearing mice. The molecular mechanisms associated with the anti-tumour therapeutic use of the nanoparticles were also elucidated.

Result
The prepared DM1-mPEG/HER-PGNSs had a size of 78.6 nm and displayed excellent colloidal stability, photothermal conversion ability and redox-sensitive drug release. These DM1-mPEG/HER-PGNSs were taken up selectively by cancer cells in vitro and accumulated at tumour sites in vivo. Moreover, the DM1-mPEG/HER-PGNSs enhanced the performance of multimodal computed tomography (CT), photoacoustic (PA) and photothermal (PT) imaging and enabled chemo-thermal combination therapy. The therapeutic mechanism involved the induction of tumour cell apoptosis via the activation of tubulin, caspase-3 and the heat shock protein 70 pathway. M2 macrophage suppression and anti-metastatic functions were also observed.

Conclusion
The prepared DM1-mPEG/HER-PGNSs enabled nanodart-like tumour targeting, visibility by CT, PA and PT imaging in vivo and powerful tumour inhibition mediated by chemo-thermal combination therapy in vivo. In summary, these unique gold nanocarriers appear to have good potential as theranostic nanoagents that can serve both as a probe for enhanced multimodal imaging and as a novel targeted anti-tumour drug delivery system to achieve precision nanomedicine for cancers.
Mitochondria-targeting graphene oxide nanocomposites for fluorescence imaging-guided synergistic phototherapy of drug-resistant osteosarcoma
Authors: Zeng Wei-Nan , Yu Qiu-Ping , Wang Duan , Liu Jun-Li , Yang Qing-Jun , Zhou Zong-Ke , Zeng Yi-Ping 
Published: March 2021

Abstract
Background
Osteosarcoma (OS) is the most common primary malignant bone tumor occurring in children and young adults. Drug-resistant osteosarcoma often results in chemotherapy failure. Therefore, new treatments aimed at novel therapeutic targets are urgently needed for the treatment of drug-resistant osteosarcoma. Mitochondria-targeted phototherapy, i.e., synergistic photodynamic/photothermal therapy, has emerged as a highly promising strategy for treating drug-resistant tumors. This study proposed a new nano-drug delivery system based on near-infrared imaging and multifunctional graphene, which can target mitochondria and show synergistic phototherapy, with preferential accumulation in tumors.

Methods and results
Based on our previous study, (4-carboxybutyl) triphenyl phosphonium bromide (TPP), a mitochondria-targeting ligand, was conjugated to indocyanine green (ICG)-loaded, polyethylenimine-modified PEGylated nanographene oxide sheets (TPP-PPG@ICG) to promote mitochondrial accumulation after cellular internalization. Thereafter, exposure to a single dose of near-infrared irradiation enabled synergistic photodynamic and photothermal therapy, which simultaneously inhibited adenosine triphosphate synthesis and mitochondrial function. Induction of intrinsic apoptosis assisted in surmounting drug resistance and caused tumor cell death. After fluorescence imaging-guided synergistic phototherapy, the mitochondria-targeting, multifunctional graphene-based, drug-delivery system showed highly selective anticancer efficiency in vitro and in vivo, resulting in marked inhibition of tumor progression without noticeable toxicity in mice bearing doxorubicin-resistant MG63 tumor cells.

Conclusion
The mitochondria-targeting TPP-PPG@ICG nanocomposite constitutes a new class of nanomedicine for fluorescence imaging-guided synergistic phototherapy and shows promise for treating drug-resistant osteosarcoma.
The performance of the EQ-5D-3L in screening for anxiety and depressive symptoms in hospital and community settings
Authors: Short Hilary , Al Sayah Fatima , Ohinmaa Arto , Johnson Jeffrey A. 
Published: March 2021

Abstract
Background
To examine the performance of the EQ-5D-3L in screening for anxiety and depressive symptoms in hospital and community settings compared to other patient-reported screening tools.

Methods
Data from a prospective cohort of patients discharged from general internal medicine wards from two hospitals in Edmonton, Alberta were used in this study. Two waves of measurements (discharge and 90-days post-discharge) were analyzed. The performance of the EQ-5D-3L was compared to other self-report screening tools: Generalized Anxiety Disorder 2-item questionnaire was used to categorize anxiety symptoms into absent (< 3) and present (≥ 3), and the Patient Health Questionnaire 9-items was used to categorize depressive symptoms by two severity cut-points: no (< 10) vs. mild (≥ 10), and no (< 15) vs. moderate-severe (≥ 15). Performance of EQ-5D-3L in screening for anxiety and depressive symptoms was evaluated using receiver operating curve (ROC) analysis.

Results
Average age of participants (n = 493) was 62.9 years (SD 18.6); 51% were female. At discharge, 30.0% screened positive for mild and 12.8% for moderate-severe depressive symptoms, while 27.6% screened positive for anxiety symptoms. For co-morbid symptoms, 17.1% screened positive for anxiety and any depressive symptoms, while 10.8% for anxiety and moderate-severe depressive symptoms. While the EQ-5D-3L had limited screening ability in hospital, the anxiety/depression dimension performed well in the community setting (90-days post-discharge) in screening for anxiety (area under ROC 0.79), depressive symptoms (any: 0.78, moderate-severe: 0.84), and a combination of both (any: 0.86; moderate-severe: 0.91).

Conclusions
The EQ-5D-3L anxiety/depression dimension could be a useful tool in screening for anxiety and depressive symptoms in community settings compared to other self-report screening tools. The usefulness of the EQ-5D-3L as a screening tool in other settings and populations is warranted.
EQ-5D self-reported health in Barbados and Jamaica with EQ-5D-5L population norms for the English-speaking Caribbean
Authors: Bailey Henry , Janssen Mathieu F. , La Foucade Althea , Boodraj Girjanauth , Wharton Marjorie , Castillo Philip 
Published: March 2021

Abstract
Background
The EQ-5D instrument is increasingly used in clinical and resource allocation decision making in developed and developing countries. EQ-5D valuation and population norms studies have been undertaken for Trinidad and Tobago, however no population norms or value sets have been generated for the other Caribbean countries. The aims of this study were to provide population norms for Barbados and Jamaica, and to develop a set of population norms that could be used by the other English-speaking Caribbean countries.

Methods
The EQ-5D-5L self-reported health questionnaire was included in surveys of representative samples of adults in Barbados and adults in Jamaica in 2013. EQ-5D health states, mean EQ VAS scores and mean EQ-5D-5L index values (using the Trinidad and Tobago value set) were calculated for demographic groups in both countries based on 2347 respondents from Barbados and 1423 from Jamaica. A set of ‘Caribbean’ norms were developed by combining the Barbados and Jamaica data with norms recently published for Trinidad and Tobago.

Results
Data were obtained for 2347 and 1423 respondents in Barbados and Jamaica respectively. The mean index and EQ VAS values were 0.943 and 81.9 for Barbados, and 0.948 and 87.8 for Jamaica. The health states most commonly observed in the two countries were similar. Generally the demographic patterns of self-reported health were consistent with those found in other studies. Some differences between the countries were observed in the patterns of rates of reporting problems on the EQ-5D dimensions among age-gender groups specifically for anxiety/depression and pain/discomfort

Conclusion
This study has produced a set of EQ-5D population norms that can be used as base-line values in clinical and clinico-economic analyses for Barbados and Jamaica and for the English-Speaking Caribbean region.
Controlled ovarian stimulation should not be preferred for male infertility treated with intrauterine insemination: a retrospective study
Authors: Tang Yan , He Qian-Dong , Zhang Ting-Ting , Wang Jing-Jing , Huang Si-Chong , Ye Yun 
Published: March 2021

Abstract
Background
Some studies have stated that intrauterine insemination (IUI) with controlled ovarian stimulation (COS) might increase the pregnancy rate, while others suggest that IUI in the natural cycle (NC) should be the first line of treatment. It remains unclear whether it is necessary to use COS at the same time when IUI is applied to treat isolated male factor infertility. Thus, we aimed to investigate efficacy of IUI with COS for isolated male factor infertility.

Methods
A total of 601 IUI cycles from 307 couples who sought medical care for isolated male factor infertility between January 2010 and February 2020 were divided into two groups: NC-IUI and COS-IUI. The COS-IUI group was further divided into two subgroups according to the number of pre-ovulatory follicles on the day of HCG: cycles with monofollicular development (one follicle group) and cycles with at least two pre-ovulatory follicles (≥ 2 follicles group). The IUI outcomes, including clinical pregnancy, live birth, spontaneous abortion, ectopic pregnancy, and multiple pregnancy rates were compared.

Results
The clinical pregnancy, live birth, spontaneous abortion, and ectopic pregnancy rates were comparable between the NC-IUI and COS-IUI group. Similar results were also observed among the NC-IUI, one follicle, and ≥ 2 follicles groups. However, with respect to the multiple pregnancy rate, a trend toward higher multiple pregnancy rate was observed in the COS-IUI group compared to the NC-IUI group (8.7% vs. 0, P = 0.091), and a significant difference was found between the NC-IUI and ≥ 2 follicles group (0 vs. 16.7%, P = 0.033).

Conclusion
In COS cycles, especially in those with at least two pre-ovulatory follicles, the multiple pregnancy rate increased without a substantial gain in overall pregnancy rate; thus, COS should not be preferred in IUI for isolated male factor infertility. If COS is required, one stimulated follicle and one healthy baby should be the goal considering the safety of both mothers and foetuses.
Neuroprotective effect of mitochondrial translocator protein ligand in a mouse model of tauopathy
Authors: Fairley Lauren H. , Sahara Naruhiko , Aoki Ichio , Ji Bin , Suhara Tetsuya , Higuchi Makoto , Barron Anna M. 
Published: March 2021

Abstract
Background
The translocator protein (TSPO) has been identified as a positron emission tomography (PET)-visible biomarker of inflammation and promising immunotherapeutic target for the treatment of Alzheimer’s disease (AD). While TSPO ligands have been shown to reduce the accumulation of the toxic Alzheimer’s beta-amyloid peptide, their effect on tau pathology has not yet been investigated. To address this, we analyzed the effects of TSPO ligand, Ro5-4864, on the progression of neuropathology in rTg4510 tau transgenic mice (TauTg).

Methods
Brain atrophy, tau accumulation, and neuroinflammation were assessed longitudinally using volumetric magnetic resonance imaging, tau-PET, and TSPO-PET, respectively. In vivo neuroimaging results were confirmed by immunohistochemistry for markers of neuronal survival (NeuN), tauopathy (AT8), and inflammation (TSPO, ionized calcium-binding adaptor molecule 1 or IBA-1, and complement component 1q or C1q) in brain sections from scanned mice.

Results
TSPO ligand treatment attenuated brain atrophy and hippocampal neuronal loss in the absence of any detected effect on tau depositions. Atrophy and neuronal loss were strongly associated with in vivo inflammatory signals measured by TSPO-PET, IBA-1, and levels of C1q, a regulator of the complement cascade. In vitro studies confirmed that the TSPO ligand Ro5-4864 reduces C1q expression in a microglial cell line in response to inflammation, reduction of which has been shown in previous studies to protect synapses and neurons in models of tauopathy.

Conclusions
These findings support a protective role for TSPO ligands in tauopathy, reducing neuroinflammation, neurodegeneration, and brain atrophy.
Next generation of immune checkpoint inhibitors and beyond
Authors: Marin-Acevedo Julian A. , Kimbrough ErinMarie O. , Lou Yanyan 
Published: March 2021

AbstractThe immune system is the core defense against cancer development and progression. Failure of the immune system to recognize and eliminate malignant cells plays an important role in the pathogenesis of cancer. Tumor cells evade immune recognition, in part, due to the immunosuppressive features of the tumor microenvironment. Immunotherapy augments the host immune system to generate an antitumor effect. Immune checkpoints are pathways with inhibitory or stimulatory features that maintain self-tolerance and assist with immune response. The most well-described checkpoints are inhibitory in nature and include the cytotoxic T lymphocyte-associated molecule-4 (CTLA-4), programmed cell death receptor-1 (PD-1), and programmed cell death ligand-1 (PD-L1). Molecules that block these pathways to enhance the host immunologic activity against tumors have been developed and become standard of care in the treatment of many malignancies. Only a small percentage of patients have meaningful responses to these treatments, however. New pathways and molecules are being explored in an attempt to improve responses and application of immune checkpoint inhibition therapy. In this review, we aim to elucidate these novel immune inhibitory pathways, potential therapeutic molecules that are under development, and outline particular advantages and challenges with the use of each one of them.