bluuebunny/crossref_metadata_2025_split huggingface dataset:
G6PD deficiency in malaria endemic areas of Nepal
Authors: Marasini Baburam , Lal Bibek Kumar , Thapa Suman , Awasthi Kiran Raj , Bajracharya Bijay , Khanal Pratik , Neupane Sanjeev , Jha Shambhu Nath , Acharya Sanjaya , Iama Smriti , Koirala Madan , Koirala Dinesh , Bhandari Suresh , Mahato Ram Kumar , Chaudhary Arun , Ghimire Pramin , Magar Rahachan Gharti , Bhattarai Rajan Kumar , Gornsawun Gornpan , Penpitchaporn Pimsupah , Bancone Germana , Acharya Bhim Prasad 
Published: August 2020

Abstract
Background
Glucose-6-phosphate dehydrogenase (G6PD) deficiency is currently a threat to malaria elimination due to risk of primaquine-induced haemolysis in G6PD deficient individuals. The World Health Organization (WHO) recommends G6PD screening before providing primaquine as a radical treatment against vivax malaria. However, evidence regarding the prevalence and causing mutations of G6PD deficiency in Nepal is scarce.

Methods
A cross-sectional, population-based, prevalence study was carried out from May to October 2016 in 12 malaria-endemic districts of Nepal. The screening survey included 4067 participants whose G6PD status was determined by G6PD Care Start™ rapid diagnostic test and genotyping.

Results
The prevalence of G6PD deficiency at the national level was 3.5% (4.1% among males and 2.1% among females). When analysed according to ethnic groups, G6PD deficiency was highest among the Janajati (6.2% overall, 17.6% in Mahatto, 7.7% in Chaudhary and 7.5% in Tharu) and low among Brahman and Chhetri (1.3%). District-wise, prevalence was highest in Banke (7.6%) and Chitwan (6.6%). Coimbra mutation (592 C>T) was found among 75.5% of the G6PD-deficient samples analysed and Mahidol (487 G>A) and Mediterranean (563 C>T) mutations were found in equal proportions in the remaining 24.5%. There was no specific geographic or ethnic distribution for the three mutations.

Conclusions
This study has identified populations with moderate to high prevalence of G6PD deficiency which provides strong evidence supporting the WHO recommendations to screen G6PD deficiency at health facility level before the use of primaquine-based radical curative regimen for Plasmodium vivax.
Stability testing of dried Plasmodium falciparum positive quality control samples for malaria rapid diagnostic tests in Liberia and Benin
Authors: Ramani Saliou , Kohar Henry T. , Pratt Oliver , Denon Yves Eric , Reed Christie M. , Thomas Peter , Powell Suzanne E. , Aidoo Michael 
Published: August 2020

Abstract
Background
Malaria rapid diagnostic tests (RDTs) are largely responsible for the gains made in the proportion of malaria cases confirmed with a parasitological test. However, quality assurance programs to support their use remain a challenge. A dried tube specimen (DTS) method was developed that showed potential for use as a stable source of quality control (QC) sample for RDTs and for use in external quality assessments or proficiency testing (PT). DTS was further assessed with focus on sample stability under field settings in Benin and Liberia.

Methods
DTS were prepared using Plasmodium falciparum 3D7 or W2 strains at concentrations of 1000, 500 or 0 parasites/µL and tested for baseline reactivity at the Centers for Disease Control and Prevention, Atlanta before shipping. In Benin and Liberia, DTS were stored under refrigeration in a reference laboratory (RL) or in health centres under ambient temperatures. Seven rounds of testing were performed at 4-week intervals during which DTS were tested on RDTs stored at the RL or at health centres. Observed DTS reactivity at the RL and health centres were compared to expected reactivity to determine DTS stability. DTS were also assembled into a PT panel and tested by health facility staff at the mid and end time-points of the study. Daily maximum and minimum storage temperatures for RDTs and DTS were recorded.

Results
In Benin, DTS, irrespective of storage conditions, produced the expected reactivity at all time points. However, evidence of degradation was observed at weeks 20 and 24 for DTS stored at ambient temperatures at the health centres and not those stored under refrigeration at the RL. In Liberia, sample degradation was observed starting at week 8 especially among DTS stored at the health facilities. The degradation was associated with prolonged storage of DTS under ambient temperature prior to study commencement and less than optimal storage temperatures at the RL. Use of DTS in a PT enabled identification of health worker errors in performing the tests.

Conclusion
DTS is a feasible tool for use as QC material and for PT under field conditions. Long-term (> 5 months) storage of DTS requires refrigeration.
Rapid identification of COVID-19 severity in CT scans through classification of deep features
Authors: Yu Zekuan , Li Xiaohu , Sun Haitao , Wang Jian , Zhao Tongtong , Chen Hongyi , Ma Yichuan , Zhu Shujin , Xie Zongyu 
Published: August 2020

AbstractBackgroundChest CT is used for the assessment of the severity of patients infected with novel coronavirus 2019 (COVID-19). We collected chest CT scans of 202 patients diagnosed with the COVID-19, and try to develop a rapid, accurate and automatic tool for severity screening follow-up therapeutic treatment.MethodsA total of 729 2D axial plan slices with 246 severe cases and 483 non-severe cases were employed in this study. By taking the advantages of the pre-trained deep neural network, four pre-trained off-the-shelf deep models (Inception-V3, ResNet-50, ResNet-101, DenseNet-201) were exploited to extract the features from these CT scans. These features are then fed to multiple classifiers (linear discriminant, linear SVM, cubic SVM, KNN and Adaboost decision tree) to identify the severe and non-severe COVID-19 cases. Three validation strategies (holdout validation, tenfold cross-validation and leave-one-out) are employed to validate the feasibility of proposed pipelines.Results and conclusionThe experimental results demonstrate that classification of the features from pre-trained deep models shows the promising application in COVID-19 severity screening, whereas the DenseNet-201 with cubic SVM model achieved the best performance. Specifically, it achieved the highest severity classification accuracy of 95.20% and 95.34% for tenfold cross-validation and leave-one-out, respectively. The established pipeline was able to achieve a rapid and accurate identification of the severity of COVID-19. This may assist the physicians to make more efficient and reliable decisions.
Levels of mannose-binding lectin (MBL) associates with sepsis-related in-hospital mortality in women
Authors: Jacobson Sofie , Larsson Peter , Åberg Anna-Maja , Johansson Göran , Winsö Ola , Söderberg Stefan 
Published: August 2020

AbstractBackgroundMannose-binding lectin (MBL) mediates the innate immune response either through direct opsonisation of microorganisms or through activation of the complement system. There are conflicting data whether MBL deficiency leads to increased susceptibility to infections or not. The aim of this study was to determine if low levels of mannose-binding lectin (MBL) predict sepsis development, sepsis severity and outcome from severe sepsis or septic shock.MethodPatients aged 18 years or more with documented sepsis within 24 h after admission to the intensive care unit were included if they had participated in a health survey and donated blood samples prior to the sepsis event. A subset of these patients had stored plasma also from the acute phase. Two matched referents free of known sepsis were selected for each case. Plasma levels MBL were determined in stored samples from health surveys (baseline) and from ICU admission (acute phase). The association between MBL and sepsis, sepsis severity and in-hospital mortality were determined with 1300 ng/mL as cut-off for low levels.ResultsWe identified 148 patients (61.5% women) with a first-time sepsis event 6.5 years (median with IQR 7.7) after participation in a health survey, of which 122 also had samples from the acute septic phase. Both high MBL levels in the acute phase (odds ratio [95% confidence interval]) (2.84 [1.20–6.26]), and an increase in MBL levels from baseline to the acute phase (3.76 [1.21–11.72]) were associated with increased risk for in-hospital death in women, but not in men (0.47 [0.11–2.06]). Baseline MBL levels did not predict future sepsis, sepsis severity or in-hospital mortality.ConclusionsAn increase from baseline to the acute phase as well as high levels in the acute phase associated with an unfavourable outcome in women.
Endometriosis: current challenges in modeling a multifactorial disease of unknown etiology
Authors: Malvezzi Helena , Marengo Eliana Blini , Podgaec Sérgio , Piccinato Carla de Azevedo 
Published: August 2020

AbstractEndometriosis is a chronic inflammatory hormone-dependent condition associated with pelvic pain and infertility, characterized by the growth of ectopic endometrium outside the uterus. Given its still unknown etiology, treatments usually aim at diminishing pain and/or achieving pregnancy. Despite some progress in defining mode-of-action for drug development, the lack of reliable animal models indicates that novel approaches are required. The difficulties inherent to modeling endometriosis are related to its multifactorial nature, a condition that hinders the recreation of its pathology and the identification of clinically relevant metrics to assess drug efficacy. In this review, we report and comment endometriosis models and how they have led to new therapies. We envision a roadmap for endometriosis research, integrating Artificial Intelligence, three-dimensional cultures and organ-on-chip models as ways to achieve better understanding of physiopathological features and better tailored effective treatments.
Kawasaki disease with a concomitant primary Epstein - Barr virus infection
Authors: Rosenfeld Nataly , Tasher Diana , Ovadia Adi , Abiri Shirly , Dalal Ilan 
Published: August 2020

AbstractBackgroundKwasaki disease (KD) is the leading cause of acquired heart disease in children in most developed countries. The cause of KD remains unknown. The presumed theory is that KD occurs due to one or more infectious agents who evoke an abnormal immunological response in susceptible individuals. Epstein - Barr virus (EBV) infection has been considered as a suspected causative agent because of the potential effect on the immune system.Case presentationA previously healthy 19 month old boy presented with a 6 day history of fever accompanied by a diffuse macular erythematous rash that appeared 1 day after. The physical examination on admission revealed bilateral non-suppurative conjunctivitis, dry fissured and injected lips without “strawberry” tongue, diffuse macular rash on the trunk, face and limbs, swelling of the hands and feet, and right cervical lymphadenopathy (2 cm in diameter). Following fulfillment of all the clinical criteria, the diagnosis of KD was made and treatment with IVIG 2 g/Kg was administered along with oral aspirin (80 mg/ kg/day). However, despite the treatment, he remained febrile for an additional 2 days with persistent clinical manifestations. Therefore, he received a second 2 g/kg IVIG course with a favorable response. On the 14th day of illness the patient became febrile again and was readmitted. Blood examinations revealed remarkable leukocytosis up to 35.7 X 109/L with 87.3% lymphocytes and the blood smear revealed atypical lymphocytes and monocytes. The liver enzymes were elevated. The serology for infectious mononucleosis from his first admission revealed: IgM CMV (+), IgG CMV (−); IgM VCA EBV (+) IgG VCA EBV (−), IgG EBNA (−). To confirm infectious mononucleosis following the administration of 2 doses of IVIG, serum EBV PCR was performed and was positive (1.6X 103cp/ml).ConclusionsWe describe here a case of KD with a concomitant primary EBV infection. To the best of our knowledge, this is the first case in western country that describes KD with acute EBV infection as confirmed by PCR. The case we described stands as a contribution in favor of the possible role of EBV in the development of KD.
A comparison of MITS counseling and informed consent processes in Pakistan, India, Bangladesh, Kenya, and Ethiopia
Authors: Feroz Anam Shahil , Paganelli Christina , Bunei Milka , Eshetu Beza , Parveen Shahana , Reza Sayyeda , Sanji Chaitali , Tikmani Shiyam Sunder , Goudar Shivaprasad S. , Goudar Guruprasad , Saleem Sarah , McClure Elizabeth M. , Goldenberg Robert L. 
Published: August 2020

AbstractGlobally, more than 5 million stillbirths and neonatal deaths occur annually. For many, the cause of death (CoD) is unknown. Minimally invasive tissue sampling (MITS) has been increasingly used in postmortem examinations for ascertaining the CoD in stillbirths and neonates. Our study compared the counseling and consent methods used in MITS projects in five countries in Africa and south Asia. Key informant interviews were conducted with researchers to describe the characteristics and backgrounds of counselors, the environment and timing of consent and perceived facilitators and barriers encountered during the consent process. Counselors at all sites had backgrounds in social science, psychology and counseling or clinical expertise in obstetrics/gynecology or pediatrics. All counsellors received training about techniques for building rapport and offering emotional support to families; training duration and methods differed across sites. Counselling environments varied significantly; some sites allocated a separate room, others counselled families at the bedside or nursing stations. All counsellors had a central role in explaining the MITS procedure to families in their local languages. Most sites did not use visual aids during the process, relying solely on verbal descriptions. In most sites, parents were approached within one hour of death. The time needed for decision making by families varied from a few minutes to 24 h. In most sites, extended family took part in the decision making. Because many parents wanted burial as soon as possible, counsellors ensured that MITS would be conducted promptly after receiving consent. Barriers to consent included decreased comprehension of information due to the emotional and psychological impact of grief. Moreover, having more family members engaged in decision-making increased the complexity of counselling and achieving consensus to consent for the procedure. While each site adapted their approach to fit the context, consistencies and similarities across sites were observed.
Network construction of aberrantly expressed miRNAs and their target mRNAs in ventricular myocardium with ischemia–reperfusion arrhythmias
Authors: Tang Jian , Gao Hong , Liu Yanqiu , Song Jing , Feng Yurong , Wang Guilong , He Youqin 
Published: August 2020

Abstract
Background
Hypothermic ischemia-reperfusion arrhythmia remains the main factor affecting cardiac resuscitation under cardiopulmonary bypass. Existing research shows that certain miRNAs exhibit significantly different expressions and effects in arrhythmias, however, the effect of miRNAs on the progression of hypothermic ischemic–reperfusion arrhythmias (RA) and its potential mechanism remain to be further explored.

Methods
Sprague-Dawley (SD) rats were randomly divided into two groups (n = 8): a normal control group (Group C) and a hypothermic ischemia-reperfusion group (Group IR), which were used to establish a Langendorff isolated cardiac perfusion model. According to the arrhythmia scoring system, rats in group IR were divided into a high-risk group (IR-H) and a low-risk group (IR-L). miRNAs expression profiles of ventricular myocardium with global hypothermic ischemia–reperfusion and those of ventricular myocardium with hypothermic ischemia–RA were established through high-throughput sequencing. Furthermore, the aberrantly expressed miRNAs in myocardium with and without hypothermic ischemia–RA were screened and verified. The target genes of these aberrantly expressed miRNAs were predicted using RNAhybrid and MiRanda software. Based on Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) databases, we determined the mRNA targets associated with these miRNAs and studied the miRNA–mRNA interaction during the cardiovascular disease progression. The aberrantly expressed miRNAs related to hypothermic ischemia–RA were validated by Real-time Quantitative polymerase chain reaction (RT-qPCR).

Results
Eight significantly aberrantly expressed miRNAs (rno-miR-122-5p, rno-miR-429, novel_miR-1, novel_miR-16, novel_miR-17, novel_miR-19, novel_miR-30, and novel_miR-43) were identified, among which six were up-regulated and two were down-regulated. Moreover, target genes and signaling pathways associated with these aberrantly expressed miRNAs were predicted and analyzed. The miRNA–mRNA interaction network graph showed that GJA1 gene was considered as the target of novel_miR-17.

Conclusions
Aberrantly expressed miRNAs were possibly associated with the formation mechanism of hypothermic ischemia–RA. Specific miRNAs, such as novel_miR-17 and rno-miR-429 are probably new potential targets for further functional studies of hypothermic ischemia–RA.
Cancer-associated adipocytes: emerging supporters in breast cancer
Authors: Zhao Chongru , Wu Min , Zeng Ning , Xiong Mingchen , Hu Weijie , Lv Wenchang , Yi Yi , Zhang Qi , Wu Yiping 
Published: August 2020

AbstractBreast cancer (BC) is a malignant breast tumor confronted with high invasion, metastasis and recurrence rate, and adipocytes are the largest components in breast tissue. The aberrant adipocytes, especially the BC-neighbored cancer-associated adipocytes (CAAs), are found in the invasive front of BC. CAAs present a vicious phenotype compared with mature mammary adipocytes and mediate the crosstalk network between adipocytes and BC cells. By releasing multiple adipokines such as leptin, adiponectin, interleukin (IL)-6, chemokine ligand 2 (CCL2) and chemokine ligand 5 (CCL5), CAAs play essential roles in favor of proliferation, angiogenesis, dissemination, invasion and metastasis of BC. This article reviews the recent existing CAAs studies on the functions and mechanisms of adipocytes in the development of BC, including adipokine regulating, metabolic reprogramming, extracellular matrix (ECM) remodeling, microRNAs (miRNAs) and immune cell adjusting. Besides, adipocyte secretome and cellular interactions are implicated in the intervention to BC therapy and autologous fat grafting of breast reconstruction. Therefore, the potential functions and mechanisms of CAAs are very important for unveiling BC oncogenesis and progress. Deciphering the complex network between CAAs and BC is critical for designing therapeutic strategies and achieving the maximum therapeutic effects of BC.
Transcriptomics of cumulus cells – a window into oocyte maturation in humans
Authors: Wyse Brandon A. , Fuchs Weizman Noga , Kadish Seth , Balakier Hanna , Sangaralingam Mugundhine , Librach Clifford L. 
Published: August 2020

Abstract
Background
Cumulus cells (CC) encapsulate growing oocytes and support their growth and development. Transcriptomic signatures of CC have the potential to serve as valuable non-invasive biomarkers for oocyte competency and potential. The present sibling cumulus-oocyte-complex (COC) cohort study aimed at defining functional variations between oocytes of different maturity exposed to the same stimulation conditions, by assessing the transcriptomic signatures of their corresponding CC. CC were collected from 18 patients with both germinal vesicle and metaphase II oocytes from the same cycle to keep the biological variability between samples to a minimum. RNA sequencing, differential expression, pathway analysis, and leading-edge were performed to highlight functional differences between CC encapsulating oocytes of different maturity.

Results
Transcriptomic signatures representing CC encapsulating oocytes of different maturity clustered separately on principal component analysis with 1818 genes differentially expressed. CCs encapsulating mature oocytes were more transcriptionally synchronized when compared with CCs encapsulating immature oocytes. Moreover, the transcriptional activity was lower, albeit not absent, in CC encapsulating mature oocytes, with 2407 fewer transcripts detected than in CC encapsulating immature (germinal vesicle - GV) oocytes. Hallmark pathways and ovarian processes that were affected by oocyte maturity included cell cycle regulation, steroid metabolism, apoptosis, extracellular matrix remodeling, and inflammation.

Conclusions
Herein we review our findings and discuss how they align with previous literature addressing transcriptomic signatures of oocyte maturation. Our findings support the available literature and enhance it with several genes and pathways, which have not been previously implicated in promoting human oocyte maturation. This study lays the ground for future functional studies that can enhance our understanding of human oocyte maturation.
HER2 expression on tumor-derived extracellular vesicles and circulating tumor cells in metastatic breast cancer
Authors: Nanou Afroditi , Zeune Leonie Laura , Bidard Francois-Clement , Pierga Jean-Yves , Terstappen Leonardus Wendelinus Mathias Marie 
Published: August 2020

Abstract
Background
Tumor-derived extracellular vesicles (tdEVs) and circulating tumor cells (CTCs) in the blood of metastatic cancer patients associate with poor outcomes. In this study, we explored the human epidermal growth factor receptor 2 (HER2) expression on CTCs and tdEVs of metastatic breast cancer patients.

Methods
Blood samples from 98 patients (CLCC-IC-2006-04 study) were originally processed with the CellSearch® system using the CTC kit and anti-HER2 as an additional marker in the staining cocktail. CTCs and tdEVs were automatically enumerated from the generated CellSearch images using the open-source ACCEPT software.

Results
CTCs and tdEVs were subdivided based on their cytokeratin (CK) and HER2 phenotype into CK+HER2−, CK−HER2+, and CK+HER2+. The inclusion of anti-HER2 increased the percentage of informative samples with ≥ 1 detectable CTC from 89 to 95%. CK− CTCs and tdEVs correlated equally well with the clinical outcome as CK+ CTCs and tdEVs. Inter- and intra-patient heterogeneity was found for the CTC/tdEV phenotypes, and the presence of 2 or 3 classes of CTCs/tdEVs was associated with worse prognosis compared to a uniform CTC/tdEV phenotype present (1 class). The use of ≥ 7% HER2+CK+ tdEVs can predict HER2 expression of the tissue with 74% sensitivity and specificity using the HER2 amplification status of the primary tumor as a classification variable.

Conclusions
HER2 can be detected on CTCs and tdEVs not expressing CK, and these CK− CTCs/tdEVs have similar clinical relevance to CTCs and tdEVs expressing CK. tdEVs perform better than CTCs in predicting the HER2 status of the primary tissue. CTC and tdEV heterogeneity in the blood of patients is inversely associated with overall survival.