bluuebunny/crossref_metadata_2025_split huggingface dataset:
A rare Down syndrome foetus with de novo 21q;21q rearrangements causing false negative results in non-invasive prenatal testing: a case report
Authors: Xu Hui-Hui , Dai Mei-Zhen , Wang Kai , Zhang Yang , Pan Fei-Yan , Shi Wei-Wu 
Published: July 2020

Abstract
Background
Non-invasive prenatal testing (NIPT) has been established as a routine prenatal screening to assess the risk of common foetal aneuploidy disorder (trisomy 21, 18, and 13). NIPT has high sensitivity and high specificity, but false positive and false negative results still exist. False negative NIPT results involving Down syndrome are rare, but have a high clinical impact on families and society.

Case presentation
We described a case of a foetus that tested “negative” for trisomy 21 (Z-score was 0.664) by NIPT based on the semiconductor sequencing platform (SSP). The foetal fraction of cell-free DNA was 16.9%; this percentage was much larger than the threshold of 4% for obtaining accurate NIPT results. However, postnatally, the newborn was diagnosed with Down syndrome with the 46,XY,der(21;21)(q10;q10),+ 21 karyotype.

Conclusions
We presented a case of false negative NIPT results, which may occur through biological mechanisms rather than poor quality, technical errors or negligence. It is imperative for clinical geneticists and their patients to understand that NIPT is still a screening test.
A methylation‐based mRNA signature predicts survival in patients with gastric cancer
Authors: Li Yang , Sun Rongrong , Zhang Youwei , Yuan Yuan , Miao Yufeng 
Published: July 2020

Abstract
Background
Evidence suggests that altered DNA methylation plays a causative role in the occurrence, progression and prognosis of gastric cancer (GC). Thus, methylated-differentially expressed genes (MDEGs) could potentially serve as biomarkers and therapeutic targets in GC.

Methods
Four genomics profiling datasets were used to identify MDEGs. Gene Ontology enrichment and Kyoto Encyclopaedia of Genes and Genomes pathway enrichment analysis were used to explore the biological roles of MDEGs in GC. Univariate Cox and LASSO analysis were used to identify survival-related MDEGs and to construct a MDEGs-based signature. The prognostic performance was evaluated in two independent cohorts.

Results
We identified a total of 255 MDEGs, including 192 hypermethylation-low expression and 63 Hypomethylation-high expression genes. The univariate Cox regression analysis showed that 83 MDEGs were associated with overall survival. Further we constructed an eight-MDEGs signature that was independent predictive of prognosis in the training cohort. By applying the eight-MDEGs signature, patients in the training cohort could be categorized into high-risk or low-risk subgroup with significantly different overall survival (HR = 2.62, 95% CI 1.71–4.02, P < 0.0001). The prognostic value of the eight-MDEGs signature was confirmed in another independent GEO cohort (HR = 1.35, 95% CI 1.03–1.78, P = 0.0302) and TCGA-GC cohort (HR = 1.85, 95% CI 1.16–2.94, P = 0.0084). Multivariate cox regression analysis proved the eight-MDEGs signature was an independent prognostic factor for GC.

Conclusion
We have thus established an innovative eight-MDEGs signature that is predictive of overall survival and could be a potentially useful guide for personalized treatment of GC patients.
RETRACTED ARTICLE: CircRNA hsa_circRNA_0000069 promotes the proliferation, migration and invasion of cervical cancer through miR-873-5p/TUSC3 axis
Authors: Zhang Shuaisai , Chen Zhengli , Sun Jinxue , An Na , Xi Qinghua 
Published: July 2020

Abstract
Background
Cervical cancer (CC) is the second leading cause of cancer deaths in women worldwide, still lacking effective biomarkers and therapies for diagnosis and treatment. CircRNAs are a class of endogenous RNAs that regulate gene expression through interacting with miRNAs, implicating in the progression of cancers. Yet the roles of circRNAs in CC are not fully characterized.

Methods
Fifty pairs of tumor and adjacent normal tissues from CC patients, as well as four CC cell lines and a normal human cervical epithelial cell line were subjected to qRT-PCR assay to assess the mRNA levels of hsa_circ_0000069. CCK-8 and colony formation assays were conducted to detect the proliferation of CC cells. Transwell assay was used to evaluate the migration and invasion capabilities of CC cells. RNA pull-down and luciferase assays were used to determine the interaction between hsa_circ_0000069 and miR-873-5p. A xenograft model of CC was established to verify the in vivo function of hsa_circ_0000069 in CC progression.

Results
We firstly demonstrated that hsa_circ_0000069 was significantly upregulated and closely related to the lymph node metastasis, and poor prognosis of CC patients. Besides, hsa_circ_0000069 promoted CC cell proliferation, migration, and invasion. The knockdown of hsa_circ_0000069 also inhibited CC tumor growth in vivo. Mechanically, we revealed that hsa_circ_0000069 functioned as an oncogene in CC, which is the sponge of miR-873-5p to facilitate the TUSC3 expression, consequently promoting CC progression.

Conclusion
We demonstrated a critical hsa_circ_0000069-miR-873-5p-TUSC3 function network involved in the CC progression, which provides mechanistic insights into the roles of CircRNAs in CC progression and a promising therapeutic target for CC treatment.
RNF181 modulates Hippo signaling and triple negative breast cancer progression
Authors: Zhou Rui , Ding Yinlu , Xue Min , Xiong Bin , Zhuang Ting 
Published: July 2020

Abstract
Background
Breast cancer ranks No. 1 in women cancer incidence, while triple negative breast cancer (TNBC) is the most aggressive and the worst prognostic subtype in all breast cancer subtypes. Compared with estrogen receptor alpha positive breast cancer, which could be well controlled by endocrine therapy, TNBC is lack of mature molecular targets for medical therapy. Thus, it is urgent and necessary to discovery the carcinogenic mechanism and potential therapeutic targets for TNBC. Recent studies reveal that Hippo/YAP signaling is an important mediator for TNBC progression. Our current study investigates the role of RING finger protein RNF181 in modulation Hippo/YAP signaling.

Methods
YAP and RN181 protein level were measured by western blot, while the Hippo classical target genes were measured by real-time PCR. WST1 assay were used to measure cell proliferation, the trans-well and wound healing were used to measure the cell migration and invasion capacity. Protein stability and ubiquitin assay were used to detect the YAP protein ubiquitin and stability. The immuno-precipitation assays were used to detect the protein interactions. Immuno-staining was used to detect the protein localization of YAP and RNF181, while the ubiquitin-based immuno-precipitation assays were used to detect the specific ubiquitination manner of YAP.

Results
Our current study identified a novel modulator-RNF181 as a positive mediator for Hippo/YAP signaling activation in TNBC. RNF181 depletion significantly inhibited TNBC cell migration, invasion and proliferation, which effect could be rescued by YAP overexpression. RNF181 depletion decreased YAP protein level and Hippo signaling target genes, such as CTGF and CYR61, in TNBC cell lines. Immuno-precipitation assay showed that RNF181 interact with YAP and promoted YAP stability by inhibition K48-linked poly-ubiquitination of YAP in TNBC cells. Besides, public available data showed that RNF181 is elevated in breast cancer and related to poor prognosis in TNBC patients.

Conclusion
Our study provides evidence to establish a non-proteolytic mechanism in modulating Hippo signaling in breast cancer. RNF181 could be an interesting marker for triple negative breast cancer prognostics and therapeutics.
Digging for care-seeking behaviour among gold miners in the Guyana hinterland: a qualitative doer non-doer analysis of social and behavioural motivations for malaria testing and treatment
Authors: Yan Shirley D. , Orkis Jennifer , Khan Sohail Saifra , Wilson Sean , Davis TrishAnn , Storey J. Douglas 
Published: July 2020

AbstractBackgroundAlthough Guyana has made significant progress toward malaria control, limited access to malaria testing and treatment services threatens those gains. Mining activities create breeding environments for mosquitoes, and the migrant and mobile mining populations are hard to reach with information and services. The Ministry of Public Health (MoPH) has trained volunteers to test and treat malaria cases in remote regions. However, it remains unclear how miners perceive these testers, the services they provide, or what their malaria care-seeking behaviour is in general. To better address these challenges, Breakthrough ACTION Guyana and MoPH conducted qualitative research from October to November 2018 in Regions 7 and 8 in Guyana.MethodsA total of 109 individuals, 70 miners, 17 other mining camp staff, and 22 other key stakeholders (e.g. community health workers, pharmacists, and regional leadership), participated in semi-structured interviews and focus group discussions. Results were derived using a framework analysis, with an adjusted doer and non-doer analysis, and organized using the integrated behaviour framework.ResultsMiners sought MoPH-approved services because of close geographic proximity to testing services, a preference for public service treatment, and a desire to correctly diagnose and cure malaria rather than just treat its symptoms. Those who chose to initiate self-treatment—using unregulated medications from the private and informal sector—did so out of convenience and the belief that self-treatment had worked before. Miners who completed the full MoPH-approved treatment understood the need to complete the treatment, while those who prematurely stopped treatment did so because of medication side effects and a desire to feel better as soon as possible.ConclusionReasons why miners do and do not pursue malaria testing and treatment services are diverse. These results can inform better MoPH programming and new solutions to improve malaria outcomes in Guyana.
Race, socioeconomic deprivation, and hospitalization for COVID-19 in English participants of a national biobank
Authors: Patel Aniruddh P. , Paranjpe Manish D. , Kathiresan Nina P. , Rivas Manuel A. , Khera Amit V. 
Published: July 2020

AbstractPreliminary reports suggest that the Coronavirus Disease 2019 (COVID− 19) pandemic has led to disproportionate morbidity and mortality among historically disadvantaged populations. We investigate the racial and socioeconomic associations of COVID− 19 hospitalization among 418,794 participants of the UK Biobank, of whom 549 (0.13%) had been hospitalized. Both Black participants (odds ratio 3.7; 95%CI 2.5–5.3) and Asian participants (odds ratio 2.2; 95%CI 1.5–3.2) were at substantially increased risk as compared to White participants. We further observed a striking gradient in COVID− 19 hospitalization rates according to the Townsend Deprivation Index − a composite measure of socioeconomic deprivation − and household income. Adjusting for socioeconomic factors and cardiorespiratory comorbidities led to only modest attenuation of the increased risk in Black participants, adjusted odds ratio 2.4 (95%CI 1.5–3.7). These observations confirm and extend earlier preliminary and lay press reports of higher morbidity in non-White individuals in the context of a large population of participants in a national biobank. The extent to which this increased risk relates to variation in pre-existing comorbidities, differences in testing or hospitalization patterns, or additional disparities in social determinants of health warrants further study.
The association of dietary patterns with endocannabinoids levels in overweight and obese women
Authors: Yagin Neda Lotfi , Hajjarzadeh Samaneh , Aliasgharzadeh Soghra , Aliasgari Fereshteh , Mahdavi Reza 
Published: July 2020

Abstract
Background
Higher levels of anandamide (AEA) and 2-arachidonoylglycerol (2-AG), the main arachidonic acid-derived endocannabinoids, are frequently reported in overweight and obese individuals. Recently, endocannabinoids have become a research interest in obesity area regarding their role in food intake. The relationship between dietary patterns and endocannabinoids is poorly understood; therefore, this study evaluated the association of the dietary patterns with AEA and 2-AG levels in overweight and obese women.

Methods
In this cross sectional study, 183 overweight and obese females from Tabriz, Iran who aged between 19 and 50 years old and with mean BMI = 32.44 ± 3.79 kg/m2 were interviewed. The AEA and 2-AG levels were measured, and the dietary patterns were assessed using food frequency questionnaire. To extract the dietary patterns, factor analysis was applied. The association between AEA and 2-AG levels and dietary patterns was analyzed by linear regression.

Results
Three major dietary patterns including “Western”, “healthy”, and “traditional” were extracted. After adjusting for age, physical activity, BMI, waist circumference, and fat mass, higher levels of AEA and 2-AG were observed in participants who were in the highest quintile of the Western pattern (P <  0.05). Also, in both unadjusted and adjusted models, significantly lower levels of AEA and 2-AG were detected in the women of the highest quintile of the healthy pattern (P <  0.01). Moreover, there was no significant association between “traditional” pattern and AEA and 2- AG levels in both unadjusted and adjusted models (P > 0.05).

Conclusion
In regard with the lower levels of endocannabinoids in healthy dietary pattern, adherence to healthy pattern might have promising results in regulating endocannabinoids levels.
Effects of sedative-hypnotics on sleep quality among patients with insomnia: evidence from an observational, pre-post study in India
Authors: Satheesh Gautam , Puthean Sandra , Sharma Abhishek , Mishra Shiva Raj , Jose Jeswin , Kakkan Sushil , Unnikrishnan M. K. 
Published: July 2020

Abstract
Background
Insomnia continues to be neglected globally, despite its high prevalence. Guidelines by the health regulatory agencies call for studies to evaluate the effect of sedative-hypnotics on sleep quality.

Methods
We conducted a pre-post observational study to evaluate sleep quality among 186 inpatients receiving short-term oral sedative-hypnotic therapy in a tertiary care teaching hospital in Kozhikode (Kerala), India. Using Pittsburgh Sleep Quality Index_Past-Week (PSQI_PW) questionnaire, patients were interviewed upon hospital admission and at follow up after ≥1-week of sedative-hypnotic therapy. Additionally, we interviewed 36 physicians to understand the current clinical perception about sedative-hypnotics.

Results
Mean (SD) age of the study patients was 59 (7.5) years. Majority (63.4%) of the patients were men. Of the various primary diagnoses for hospitalization, cardiovascular disease was the most common (22.6%, n = 49). Sedative-hypnotic therapy improved the mean (SD) PSQI_PW overall score by 6.79 points (pre: 12.70 (3.5) vs. post: 5.91 (2.8); p < 0.0001). Statistically significant improvements in sleep duration, latency, efficacy, and day dysfunction were observed. Higher proportion of study patients were prescribed benzodiazepines (73.7%) compared to zolpidem (26.3%). Patients treated with zolpidem reported higher improvements in mean overall PSQI_PW scores compared to those treated with benzodiazepines, however these differences were not statistically significant upon adjusting for age, gender and primary diagnosis for hospitalization. Qualitative interviews indicate that that physicians consider zolpidem to be safer and more efficacious.

Conclusions
In our study, sedative-hypnotic therapy helped improve sleep quality among the hospitalized patients. More studies evaluating the comparative efficacy and safety of zolpidem vs. benzodiazepines – including among patient groups with varying demographic and clinical characteristics – are needed. India must develop evidence-based treatment guidelines to inform the clinical practice around the use of sedative-hypnotics.
Rapid exacerbation featuring acute leukemoid reaction after retrolaparoscopic nephrectomy: a rare case report of renal cell carcinoma with postoperative comprehensive genomic profiling
Authors: Zhang Xuhui , Yan Lijuan , Yuan Xiaobin , Bai Tao , Zhang Lei , Han Shuaihong 
Published: July 2020

Abstract
Background
Rapid lethal exacerbation and recurrence featuring acute leukemoid reaction (ALR) after retrolaparoscopic radical nephrectomy (RN) is a relatively rare clinical incident. Performing the reoperation for the patient and analyzing the tissue-based genetic mutation information postoperatively are a skill-demanding and meaningful task, which have been even more rarely reported.

Case presentation
We present a case with a large right renal mass (13.0 × 10.0 × 8.0 cm). This 71-year-old male patient underwent the retrolaparoscopic RN in our department. The operation was technically precise and successful with final pathological diagnosis of hybrid (clear cell and papillary type) renal cell carcinoma (RCC). However, 10 days after the patient was discharged, he was readmitted with the chief complaint of high fever with severe right flank pain. CT scanning revealed that right retroperitoneal hematoma and the blood routine showed the dramatic elevation of white blood cell count (WBC). Even though the immediate broad-spectrum antibiotics were administered without delay and subsequent percutaneous puncturing and drainage was performed, the patient’s condition still exacerbated rapidly. In spite of the reoperation of hematoma evacuation, the patient died of multiple organ failure 10 days after the reoperation. The pathological result of reoperation showed the necrotic and hematoma tissue blended with RCC tumor cells (nuclear grading III), and both of the postoperative tissue-originated comprehensive genomic profiling by using the specimens from the RN and reoperation respectively indicated significant mutations of some oncogenes which might have potential relevance with ALR. Besides, both of the immunohistochemical (IHC) staining results from primary surgical renal mass and reoperative resected tissue revealed the positive expressions of granulocyte colony-stimulating factor (G-CSF).

Conclusions
ALR may be a predictor of poor prognosis in patients with RCC, and comprehensive genomic profiling as well as the alterative expression of G-CSF can help to provide potential valuable genetic etiological information and evidence for guiding the potential effective molecular-targeting therapy.
Can we walk away from cardiovascular disease risk or do we have to ‘huff and puff’? A cross-sectional compositional accelerometer data analysis among adults and older adults in the Copenhagen City Heart Study
Authors: Johansson Melker Staffan , Søgaard Karen , Prescott Eva , Marott Jacob Louis , Schnohr Peter , Holtermann Andreas , Korshøj Mette 
Published: July 2020

AbstractBackgroundIt is unclear whether walking can decrease cardiovascular disease (CVD) risk or if high intensity physical activity (HIPA) is needed, and whether the association is modified by age. We investigated how sedentary behaviour, walking, and HIPA, were associated with systolic blood pressure (SBP), waist circumference (WC), and low-density lipoprotein cholesterol (LDL-C) among adults and older adults in a general population sample using compositional data analysis. Specifically, the measure of association was quantified by reallocating time between sedentary behaviour and 1) walking, and 2) HIPA.MethodsCross-sectional data from the fifth examination of the Copenhagen City Heart Study was used. Using the software Acti4, we estimated daily time spent in physical behaviours from accelerometer data worn 24 h/day for 7 days (i.e., right frontal thigh and iliac crest; median wear time: 6 days, 23.8 h/day). SBP, WC, and LDL-C were measured during a physical examination. Inclusion criteria were ≥ 5 days with ≥16 h of accelerometer recordings per day, and no use of antihypertensives, diuretics or cholesterol lowering medicine. The 24-h physical behaviour composition consisted of sedentary behaviour, standing, moving, walking, HIPA (i.e., sum of climbing stairs, running, cycling, and rowing), and time in bed. We used fitted values from linear regression models to predict the difference in outcome given the investigated time reallocations relative to the group-specific mean composition.ResultsAmong 1053 eligible participants, we found an interaction between the physical behaviour composition and age. Age-stratified analyses (i.e., </≥65 years; 773 adults, 280 older adults) indicated that less sedentary behaviour and more walking was associated with lower SBP among older adults only. For less sedentary behaviour and more HIPA, the resultsi)indicated an association with a lower SBP irrespective of age,ii)showed an association with a smaller WC among adults, andiii)showed an association with a lower LDL-C in both age groups.ConclusionsLess sedentary behaviour and more walking seems to be associated with lower CVD risk among older adults, while HIPA types are associated with lower risk among adults. Therefore, to reduce CVD risk, the modifying effect of age should be considered in future physical activity-promoting initiatives.
JC Polyomavirus, progressive multifocal leukoencephalopathy and immune reconstitution inflammatory syndrome: a review
Authors: Harypursat Vijay , Zhou Yihong , Tang Shengquan , Chen Yaokai 
Published: July 2020

AbstractThe human neurotropic virus JC Polyomavirus, a member of the Polyomaviridae family, is the opportunistic infectious agent causing progressive multifocal leukoencephalopathy, typically in immunocompromised individuals. The spectrum of underlying reasons for the systemic immunosuppression that permits JCV infection in the central nervous system has evolved over the past 2 decades, and therapeutic immunosuppression arousing JCV infection in the brain has become increasingly prominent as a trigger for PML. Effective immune restoration subsequent to human immunodeficiency virus-related suppression is now recognized as a cause for unexpected deterioration of symptoms in patients with PML, secondary to a rebound inflammatory phenomenon called immune reconstitution inflammatory syndrome, resulting in significantly increased morbidity and mortality in a disease already infamous for its lethality. This review addresses current knowledge regarding JC Polyomavirus, progressive multifocal leukoencephalopathy, progressive multifocal leukoencephalopathy-related immune reconstitution inflammatory syndrome, and the immunocompromised states that incite JC Polyomavirus central nervous system infection, and discusses prospects for the future management of these conditions.