bluuebunny/crossref_metadata_2025_split huggingface dataset:
Curative vs targeted therapy for SCD: does it make more sense to address the root cause than target downstream events?
Authors: Telen Marilyn J. 
Published: July 2020

AbstractSickle cell disease (SCD) places a heavy burden on a global and increasing population predominantly resident in resource-poor and developing countries. Progress continues to be made in preventing childhood mortality, and increasing numbers of chronically ill adults with disease are requiring care for disease sequelae. Curative therapies for SCD are therefore attractive to physicians and investigators focused on SCD. Gene therapies are being developed, and several are now in various stages of early-phase human clinical trials. However, we must also pursue avenues through which we can do the most good for the most people alive today. Such efforts include improving our understanding of disease mechanisms and which disease sequelae most strongly affect survival and interfere with quality of life. The pathways leading to disease sequelae are multiple, complex, and highly interactive. Four drugs have now been approved by the US Food and Drug Administration for SCD; however, each has a distinct mechanism and a measurable but limited effect on the many clinical sequelae of SCD. We therefore need to learn how to approach multi-agent therapy for SCD. The order of addition of each agent to treat a specific patient will need to be guided by response to previous therapy, risk factors identified for specific disease outcomes, and clinical studies to determine more comprehensively how the 4 currently approved drugs might interact and produce (or not) additive effects. Moreover, this will have to be accomplished with defined end points in mind, according to which pose the greatest threats to quality of life as well as survival.
Ischemic stroke in patients with POEMS syndrome
Authors: Feng Jun , Gao Xue-min , Zhao Hao , He Tian-hua , Zhang Cong-li , Shen Kai-ni , Zhang Lu , Cao Xin-xin , Qian Ming , Zhou Dao-bin , Li Jian 
Published: July 2020

AbstractPolyneuropathy, organomegaly, endocrinopathy, monoclonal plasma cell disorder, and skin changes (POEMS) syndrome is associated with increased risk for ischemic stroke (IS). Because POEMS syndrome is rare, little is known regarding the underlying mechanism and prognosis for IS in patients in whom it occurs. The medical records of patients with POEMS syndrome were screened between January 2018 and January 2000 at Peking Union Medical College Hospital to identify those with IS. The baseline characteristics, IS features, and patient outcomes were analyzed. Forty-one (8.0%) of 510 POEMS patients were documented to have IS. Patients with IS were older, had a higher percentage of Overall Neuropathy Limitation Scale score &gt;4, and had a higher level of fibrinogen compared with those who did not have IS. Ninety-three percent of IS events occurred before or within 3 months after a diagnosis of POEMS. Of 41 occurrences of IS, 29 (46.3%) were multifocal. Recurrent IS was observed in 13 (31.7%) of 41 patients, but not in patients with successful anti-plasma cell therapy. The 3-year overall survival rate in patients with IS was 71.0% and for those without IS, it was 88.5% (P = .002). We showed that 8.0% of POEMS patients had IS, and most IS events occurred in POEMS patients not being treated effectively. Having IS was a predictor of unfavorable prognosis. Early diagnosis, immediate initiation of treatment for POEMS, and control of POEMS syndrome is key to reducing the occurrence of IS, improving survival, and preventing recurrence of IS.
Survival outcomes in blastic plasmacytoid dendritic cell neoplasm by first-line treatment and stem cell transplant
Authors: Yun Seongseok , Chan Onyee , Kerr Daniel , Vincelette Nicole D. , Idrees Afshan , Mo Qianxing , Sweet Kendra , Lancet Jeffrey E. , Kharfan-Dabaja Mohamed A. , Zhang Ling , Sokol Lubomir 
Published: July 2020

Abstract
Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare hematologic malignancy with dismal clinical outcomes. Conventional chemotherapies such cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) and hyperfractionated cyclophosphamide, vincristine, doxorubicin, dexamethasone alternating with high-dose cytarabine and methotrexate (CVAD) have been commonly used for the BPDCN treatment until a recent study showed promising outcomes in patients treated with SL-401 (Tagraxofusp). In this single-institution retrospective study, we identified a total of 49 consecutive BPDCN patients. Among 42 patients who received treatment, hyper-CVAD regimen was associated with higher complete response rate compared with CHOP-based regimens or SL-401 (91% vs 50% vs 50%), although the difference did not achieve statistical significance. Furthermore, there was no significant overall survival (OS) difference between patients treated with SL-401 vs other chemotherapies as their first-line treatment (hazard ratio = 1.597; 95% CI, 0.460-5.548; P = .431). Of note, patients who received allogeneic stem cell transplant (allo-SCT) had significantly longer OS (hazard ratio = 0.160; 95% CI, 0.0453-0.56; P = .041). Extent of disease (skin vs bone marrow vs both) or younger age (&lt;60 years old) did not have significant prognostic impact on OS. Collectively, our study confirmed the survival benefit of allo-SCT and suggests that conventional and intensive chemotherapies such as CHOP and hyper-CVAD as well as SL-401 would be comparable first-line choice for the BPDCN patients.
Evaluating metagenomics tools for genome binning with real metagenomic datasets and CAMI datasets
Authors: Yue Yi , Huang Hao , Qi Zhao , Dou Hui-Min , Liu Xin-Yi , Han Tian-Fei , Chen Yue , Song Xiang-Jun , Zhang You-Hua , Tu Jian 
Published: July 2020

AbstractBackgroundShotgun metagenomics based on untargeted sequencing can explore the taxonomic profile and the function of unknown microorganisms in samples, and complement the shortage of amplicon sequencing. Binning assembled sequences into individual groups, which represent microbial genomes, is the key step and a major challenge in metagenomic research. Both supervised and unsupervised machine learning methods have been employed in binning. Genome binning belonging to unsupervised method clusters contigs into individual genome bins by machine learning methods without the assistance of any reference databases. So far a lot of genome binning tools have emerged. Evaluating these genome tools is of great significance to microbiological research. In this study, we evaluate 15 genome binning tools containing 12 original binning tools and 3 refining binning tools by comparing the performance of these tools on chicken gut metagenomic datasets and the first CAMI challenge datasets.ResultsFor chicken gut metagenomic datasets, original genome binner MetaBat, Groopm2 and Autometa performed better than other original binner, and MetaWrap combined the binning results of them generated the most high-quality genome bins. For CAMI datasets, Groopm2 achieved the highest purity (> 0.9) with good completeness (> 0.8), and reconstructed the most high-quality genome bins among original genome binners. Compared with Groopm2, MetaBat2 had similar performance with higher completeness and lower purity. Genome refining binners DASTool predicated the most high-quality genome bins among all genomes binners. Most genome binner performed well for unique strains. Nonetheless, reconstructing common strains still is a substantial challenge for all genome binner.ConclusionsIn conclusion, we tested a set of currently available, state-of-the-art metagenomics hybrid binning tools and provided a guide for selecting tools for metagenomic binning by comparing range of purity, completeness, adjusted rand index, and the number of high-quality reconstructed bins. Furthermore, available information for future binning strategy were concluded.
The molecular effect of a polymorphic microRNA binding site of Wolfram syndrome 1 gene in dogs
Authors: Koller Dora , Kubinyi Eniko , Elek Zsuzsanna , Nemeth Helga , Miklosi Adam , Sasvari-Szekely Maria , Ronai Zsolt 
Published: July 2020

Abstract
Background
Although the molecular function of wolframin remains unclear, the lack of this protein is known to cause stress in the endoplasmic reticulum. Some variants in the Wolfram Syndrome 1 gene (WFS1) were associated with various neuropsychiatric disorders in humans, such as aggressiveness, impulsivity and anxiety.

Results
Here we present an in silico study predicting a single nucleotide polymorphism (rs852850348) in the canine WFS1 gene which was verified by direct sequencing and was genotyped by a PCR-based technique. We found that the rs852850348 polymorphism is located in a putative microRNA (cfa-miR-8834a and cfa-miR-1838) binding site. Therefore, the molecular effect of allelic variants was studied in a luciferase reporter system that allowed assessing gene expression. We demonstrated that the variant reduced the activity of the reporter protein expression in an allele-specific manner. Additionally, we performed a behavioral experiment and investigated the association with this locus to different performance in this test. Association was found between food possessivity and the studied WFS1 gene polymorphism in the Border collie breed.

Conclusions
Based on our findings, the rs852850348 locus might contribute to the genetic risk of possessivity behavior of dogs in at least one breed and might influence the regulation of wolframin expression.
Wogonin inhibits in vitro herpes simplex virus type 1 and 2 infection by modulating cellular NF-κB and MAPK pathways
Authors: Chu Ying , Lv Xiaowen , Zhang Longfeng , Fu Xingli , Song Siwei , Su Airong , Chen Deyan , Xu Lianhong , Wang Yongfang , Wu Zhiwei , Yun Zhihua 
Published: July 2020

Abstract
Background
Wogonin, a natural flavonoid-like chemical compound, exhibits anti-inflammatory, antitumor, antiviral, neuroprotective, and anxiolytic effects by modulating a variety of cellular signaling pathways including PI3K-Akt, p53, nuclear factor κB (NF-κB), mitogen-activated protein kinase (MAPK) pathways. In this study, its antiviral effect against herpes simplex virus (HSV) type 1 and 2 (HSV-1 and HSV-2) replication was investigated.

Results
Wogonin suppressed HSV-2-induced cytopathic effect (CPE) and reduced viral mRNA transcription, viral protein synthesis, and infectious virion particle titers in a dose-dependent manner. A time-of-drug-addition assay demonstrated that wogonin acted as a postentry viral inhibitor. Wogonin also significantly reduced HSV-induced NF-κB and MAPK pathway activation, which has previously been demonstrated to be important for viral replication.

Conclusions
Our results suggest that the anti-herpes effect of wogonin may be mediated by modulation of cellular NF-κB and JNK/p38 MAPK pathways and imply that wogonin may be useful as an anti-HSV agent.
Functional probiotics of lactic acid bacteria from Hu sheep milk
Authors: Chen Taohong , Wang Leli , Li Qinxin , Long Yingjie , Lin Yuming , Yin Jie , Zeng Yan , Huang Le , Yao Tingyu , Abbasi Muhammad Nazeer , Yang Huansheng , Wang Qiye , Tang Congjia , Khan Tahir Ali , Liu Qiuyue , Yin Jia , Tu Qiang , Yin Yulong 
Published: July 2020

Abstract
Background
Probiotics are being considered as valuable microorganisms related to human health. Hu sheep is referred as one of the important sheep breeds in China. Goat milk produced by Hu sheep is characterized with high nutritional value and hypoallergenic in nature. Particularly, this milk contains plenty of milk prebiotic and probiotic bacteria. This study was aimed to scrutinize more bacterial strains from Hu sheep milk with potential probiotic activity.

Results
Based on 16S rRNA sequence analysis, pool of forty bacterial strains were identified and evaluated their antimicrobial activities against Staphylococcus aureus, enterohemorrhagic Escherichia coli (EHEC), Salmonella typhimurium, Listeria monocytogenes enterotoxigenic E. coli (ETEC) and Aeromonas caviae. Four out of these isolated strains demonstrated their efficient bacteriostatic ability and potential healthy properties. We also examined the safety aspects of these bacterial candidates including three Lactococcus lactis strains (named as HSM-1, HSM-10, and HSM-18) and one Leuconostoc lactis strain (HSM-14), and were further evaluated via in vitro tests, including antimicrobial activity, cell surface characteristics (hydrophobicity, co-aggregation, and self-aggregation), heat treatment, antibiotic susceptibility, simulated transport tolerance in the gastrointestinal tract, and acid/bile tolerance. The obtained results revealed that HSM-1, HSM-10, HSM-14, and HSM-18 showed high survival rate at different conditions for example low pH, presence of bovine bile and demonstrated high hydrophobicity. Moreover, HSM-14 had an advantage over other strains in terms of gastrointestinal tract tolerance, antimicrobial activities against pathogens, and these results were significantly better than other bacterial candidates.

Conclusion
Hu sheep milk as a source of exploration of potential lactic acid bacteria (LAB) probiotics open the new horizon of probiotics usage from unconventional milk sources. The selected LAB strains are excellent probiotic candidates which can be used for animal husbandry in the future. Rationale of the study was to utilize Hu sheep milk as a source of potential probiotic LABs. The study has contributed to the establishment of a complete bacterial resource pool by exploring the Hu sheep milk microflora.
Seed dormancy release of Halenia elliptica in response to stratification temperature, duration and soil moisture content
Authors: Chen Da Li , Luo Xin Ping , Yuan Zhen , Bai Meng Jie , Hu Xiao Wen 
Published: July 2020

Abstract
Background
Although the effect of cold stratification on seed dormancy release has been extensively studied for many species, knowledge of the role of stratifying temperature, soil moisture content and duration of stratification on seed dormancy release at the population level is limited. Here, we aimed to determine the response of seed dormancy release to these factors in six populations of Halenia elliptica.

Results
Seed dormancy release was more responsive to low than high temperatures, and no dormancy break occurred at 8 °C. Seed germination percentage increased first and then remained unchanged as stratifying soil moisture content increased from 0 to 24%. Seed dormancy release of populations from low altitude was more sensitive to increased stratifying temperature and decreased soil moisture content than those from high altitudes.

Conclusions
Temperature and soil moisture changes resulting from global warming could affect seed dormancy release and consequently seedling establishment. Thus, incorporating data on seed dormancy release involving temperature, soil moisture content and stratification duration is beneficial for predicting plant species regeneration, migration and coexistence in a scenario of climate change.
Relative contribution of muscle strength, lean mass, and lower extremity motor function in explaining between-person variance in mobility in older adults
Authors: Wages Nathan P. , Simon Janet E. , Clark Leatha A. , Amano Shinichi , Russ David W. , Manini Todd M. , Clark Brian C. 
Published: July 2020

AbstractBackgroundApproximately 35% of individuals > 70 years have mobility limitations. Historically, it was posited lean mass and muscle strength were major contributors to mobility limitations, but recent findings indicate lean mass and muscle strength only moderately explain mobility limitations. One likely reason is that lean mass and muscle strength do not necessarily incorporate measures globally reflective of motor function (defined as the ability to learn, or to demonstrate, the skillful and efficient assumption, maintenance, modification, and control of voluntary postures and movement patterns). In this study we determined the relative contribution of lean mass, muscle strength, and the four square step test, as an index of lower extremity motor function, in explaining between-participant variance in mobility tasks.MethodsIn community-dwelling older adults (N = 89; 67% women; mean 74.9 ± 6.7 years), we quantified grip and leg extension strength, total and regional lean mass, and time to complete the four square step test. Mobility was assessed via 6-min walk gait speed, stair climb power, 5x-chair rise time, and time to complete a complex functional task. Multifactorial linear regression modeling was used to determine the relative contribution (via semi-partial r2) for indices of lean mass, indices of muscle strength, and the four square step test.ResultsWhen aggregated by sex, the four square step test explained 17–34% of the variance for all mobility tasks (p <  0.01). Muscle strength explained ~ 12% and ~ 7% of the variance in 6-min walk gait speed and 5x-chair rise time, respectively (p <  0.02). Lean mass explained 32% and ~ 4% of the variance in stair climb power and complex functional task time, respectively (p <  0.02). When disaggregated by sex, lean mass was a stronger predictor of mobility in men.ConclusionThe four square step test is uniquely associated with multiple measures of mobility in older adults, suggesting lower extremity motor function is an important factor for mobility performance.Trial registrationNCT02505529–2015/07/22.
Prevalence, related factors and maternal outcomes of primary postpartum haemorrhage in governmental hospitals in Kabul-Afghanistan
Authors: Shahbazi Sighaldeh Shirin , Nazari Adela , Maasoumi Raziyeh , Kazemnejad Anoshirvan , Mazari Ziba 
Published: July 2020

AbstractBackgroundTo determine the prevalence, related factors and maternal outcomes of primary PPH in governmental hospitals in Kabul Afghanistan.MethodsAn observational study was designed to determine the prevalence, related factors and maternal outcomes of primary PPH in governmental hospitals in Kabul-Afghanistan. The population of this study consisted of all women who gave birth to a child between August and October 2018. The structured checklist was used to collect the data from patients who were suffering from primary PPH.ResultsAmong the 8652 women who were observed, 215 (2.5%) of them suffered from primary PPH and 2 (0.9%) of them died under caesarean section. The most common related factors of primary PPH were uterine atonia (65.6%), previous PPH (34.9%), prolonged labor (27%), genital tract trauma (26.5%), and induction of labor (20.5%). The most common maternal outcomes of primary PPH were respiratory failure (7%), hysterectomy (6%), and hypovolaemic shock (5.1%).ConclusionsAccording to our findings, the major cause of postpartum bleeding was uterine atonia. Therefore, postpartum care of women is essential, especially for those with previous PPH and prolonged labor that require more attention.
Low dose environmental radon exposure and breast tumor gene expression
Authors: Peng Cheng , DuPre Natalie , VoPham Trang , Heng Yujing J. , Baker Gabrielle M. , Rubadue Christopher A. , Glass Kimberly , Sonawane Abhijeet , Zeleznik Oana , Kraft Peter , Hankinson Susan E. , Eliassen A. Heather , Hart Jaime E. , Laden Francine , Tamimi Rulla M. 
Published: July 2020

AbstractBackgroundThe International Agency for Research on Cancer classified radon and its decay-products as Group-1-human-carcinogens, and with the current knowledge they are linked specifically to lung cancer. Biokinetic models predict that radon could deliver a carcinogenic dose to breast tissue. Our previous work suggested that low-dose radon was associated with estrogen-receptor (ER)-negative breast cancer risk. However, there is limited research to examine the role of radon in breast cancer biology at the tissue level. We aim to understand molecular pathways linking radon exposure with breast cancer biology using transcriptome-wide-gene-expression from breast tumor and normal-adjacent tissues.MethodsOur study included 943 women diagnosed with breast cancer from the Nurses’ Health Study (NHS) and NHSII. We estimated cumulative radon concentration for each participant up-to the year of breast cancer diagnosis by linking residential addresses with a radon exposure model. Transcriptome-wide-gene-expression was measured with the Affymetrix-Glue-Human-Transcriptome-Array-3.0 and Human-Transcriptome-Array-2.0. We performed covariate-adjusted linear-regression for individual genes and further employed pathway-analysis. All analyses were conducted separately for tumor and normal-adjacent samples and by ER-status.ResultsNo individual gene was associated with cumulative radon exposure in ER-positive tumor, ER-negative tumor, or ER-negative normal-adjacent tissues at FDR < 5%. In ER-positive normal-adjacent samples,PLCH2—reached transcriptome-wide-significance (FDR < 5%). Gene-set-enrichment-analyses identified 2-upregulated pathways (MAPK signaling and phosphocholine biosynthesis) enriched at FDR < 25% in ER-negative tumors and normal-adjacent tissues, and both pathways have been previously reported to play key roles in ionizing radiation induced tumorigenesis in experimental settings.ConclusionOur findings provide insights into the molecular pathways of radon exposure that may influence breast cancer etiology.
The support and information needs of adolescents and young adults with cancer when active treatment ends
Authors: Lea Sarah , Martins Ana , Fern Lorna A. , Bassett Matthew , Cable Maria , Doig Gary , Morgan Sue , Soanes Louise , Whelan Michael , Taylor Rachel M. 
Published: July 2020

Abstract
Background
The end of active treatment is a period of high stress for young people with cancer, but limited literature exists about their information and support needs during this phase. This study aimed to understand the needs of young people with cancer, how these needs are currently being met, and how best to provide information and support at the end of active treatment.

Methods
This was a multi-stage, mixed methods study exploring the end of treatment experience from the perspectives of young people, and the healthcare professionals caring for them. Semi-structured interviews were undertaken with healthcare professionals, which informed a survey administered nationally. Subsequently, semi-structured interviews were conducted with young people. These combined results informed a co-design workshop to develop recommendations.

Results
Telephone interviews were conducted with 12 healthcare professionals and 49 completed the online survey. A total of 11 young people aged 19–26 years (female = 8; 73%) were interviewed. The stakeholder workshop was attended by both healthcare professionals (n = 8) and young people (n = 3). At the end of treatment young people experience numerous ongoing physical issues including pain, fatigue and insomnia; in addition to a range of psychosocial and emotional issues including anxiety, fear of recurrence and isolation. The top three priorities for end of treatment care were: earlier provision and preparation around on-going impact of cancer and cancer treatment; standardised and continued follow-up of young people’s emotional well-being; and development of more information and resources specific to young people.

Conclusion
The access and availability of appropriate information and sources of support at the end of treatment is variable and inequitable. Young people’s needs would be more effectively met by timely, structured and accessible information, and support provision at the end of treatment to both prepare and enable adaptation across their transition to living with and beyond cancer. This will require both organisational and practical adjustments in care delivery, in addition to a renewed and updated understanding of what the ‘end of treatment’ transition process means.