bluuebunny/crossref_metadata_2025_split huggingface dataset:
Nebulised heparin as a treatment for COVID-19: scientific rationale and a call for randomised evidence
Authors: van Haren Frank M. P. , Page Clive , Laffey John G. , Artigas Antonio , Camprubi-Rimblas Marta , Nunes Quentin , Smith Roger , Shute Janis , Carroll Mary , Tree Julia , Carroll Miles , Singh Dave , Wilkinson Tom , Dixon Barry 
Published: July 2020

AbstractNebulised unfractionated heparin (UFH) has a strong scientific and biological rationale and warrants urgent investigation of its therapeutic potential, for COVID-19-induced acute respiratory distress syndrome (ARDS). COVID-19 ARDS displays the typical features of diffuse alveolar damage with extensive pulmonary coagulation activation resulting in fibrin deposition in the microvasculature and formation of hyaline membranes in the air sacs. Patients infected with SARS-CoV-2 who manifest severe disease have high levels of inflammatory cytokines in plasma and bronchoalveolar lavage fluid and significant coagulopathy. There is a strong association between the extent of the coagulopathy and poor clinical outcomes.The anti-coagulant actions of nebulised UFH limit fibrin deposition and microvascular thrombosis. Trials in patients with acute lung injury and related conditions found inhaled UFH reduced pulmonary dead space, coagulation activation, microvascular thrombosis and clinical deterioration, resulting in increased time free of ventilatory support. In addition, UFH has anti-inflammatory, mucolytic and anti-viral properties and, specifically, has been shown to inactivate the SARS-CoV-2 virus and prevent its entry into mammalian cells, thereby inhibiting pulmonary infection by SARS-CoV-2. Furthermore, clinical studies have shown that inhaled UFH safely improves outcomes in other inflammatory respiratory diseases and also acts as an effective mucolytic in sputum-producing respiratory patients. UFH is widely available and inexpensive, which may make this treatment also accessible for low- and middle-income countries.These potentially important therapeutic properties of nebulised UFH underline the need for expedited large-scale clinical trials to test its potential to reduce mortality in COVID-19 patients.
Automated vs. conventional ventilation in the ICU: a randomized controlled crossover trial comparing blood oxygen saturation during daily nursing procedures (I-NURSING)
Authors: Chelly Jonathan , Mazerand Sandie , Jochmans Sebastien , Weyer Claire-Marie , Pourcine Franck , Ellrodt Olivier , Thieulot-Rolin Nathalie , Serbource-Goguel Jean , Sy Oumar , Vong Ly Van Phach , Monchi Mehran 
Published: July 2020

Abstract
Background
Hypoxia is common during daily nursing procedures (DNPs) routinely performed on mechanically ventilated patients. The impact of automated ventilation on the incidence and severity of blood oxygen desaturation during DNPs remains unknown.

Methods
A prospective randomized controlled crossover trial was carried out in a French intensive care unit to compare blood oxygen pulse saturation (SpO2) during DNPs performed on patients mechanically ventilated in automated and conventional ventilation modes (AV and CV, respectively). All patients with FiO2 ≤ 60% and without prone positioning or neuromuscular blocking agents were included. Patients underwent two DNPs on the same day using AV (INTELLiVENT-ASV®) and CV (volume control, biphasic positive airway pressure, or pressure support ventilation) in a randomized order. The primary outcome was the percentage of time spent with SpO2 in the acceptable range of 90–95% during the DNP.

Results
Of the 265 included patients, 93% had been admitted for a medical pathology, the majority for acute respiratory failure (52%). There was no difference between the two periods in terms of DNP duration, sedation requirements, or ventilation parameters, but patients had more spontaneous breaths and lower peak airway pressures during the AV period (p <  0.001). The percentage of time spent with SpO2 in the acceptable range during DNPs was longer in the AV period than in the CV period (48 ± 37 vs. 43 ± 37, percentage of DNP period; p = 0.03). After adjustment, AV was associated with a higher number of DNPs carried out with SpO2 in the acceptable range (odds ratio, 1.82; 95% CI, 1.28 to 2.6; p = 0.001) and a lower incidence of blood oxygen desaturation ≤ 85% (adjusted odds ratio, 0.50; 95% CI, 0.30 to 0.85; p = 0.01).

Conclusion
AV appears to reduce the incidence and severity of blood oxygen desaturation during daily nursing procedures (DNPs) in comparison to CV.

Trial registration
This study was registered in clinical-trial.gov (NCT03176329) in June 2017.

Graphical abstract
Erythrocyte membrane fatty acids and breast cancer risk by tumor tissue expression of immuno-inflammatory markers and fatty acid synthase: a nested case-control study
Authors: McGee Emma E. , Kim Claire H. , Wang Molin , Spiegelman Donna , Stover Daniel G. , Heng Yujing J. , Collins Laura C. , Baker Gabrielle M. , Farvid Maryam S. , Schedin Pepper , Jindal Sonali , Tamimi Rulla M. , Eliassen A. Heather 
Published: July 2020

Abstract
Background
Previous studies of fatty acids and breast cancer risk have shown mixed results, which may be due in part to tumor heterogeneity. Prior research has also illustrated an important role of specific fatty acids in immune regulation, T cell function, and inflammation, indicating that the effects of specific fatty acids on breast cancer risk may vary by tumor expression of immuno-inflammatory markers. We therefore aimed to evaluate the relationships between prediagnostic erythrocyte membrane fatty acids and breast cancer risk by tumor tissue expression of immuno-inflammatory markers (CD4, CD8, CD20, CD163, COX-2) and fatty acid synthase (FAS).

Methods
We conducted a matched case-control study nested within the Nurses’ Health Study II (n = 235 cases and 235 controls). Blood samples were collected from 1996 to 1999. Tumor tissue blocks were collected for cases diagnosed after blood collection and through 2006. Unconditional nominal polytomous logistic regression adjusted for matching factors and potential confounders was used to assess whether associations between fatty acids and breast cancer risk varied by tumor expression subtype, ascertained via immunohistochemistry. Odds ratios (OR) and 95% confidence intervals (CI) were estimated separately by tumor expression subtype using unconditional logistic regression.

Results
Associations between fatty acids and breast cancer risk did not vary substantially by tumor CD4, CD20, CD163, or COX-2. However, n-3 polyunsaturated fatty acids (PUFAs) were inversely associated with CD8low but not CD8high cancers (CD8low ORT3 vs T1 = 0.45, 95% CI 0.23–0.87, Ptrend = 0.02; CD8high ORT3 vs T1 = 1.19, 95% CI 0.62–2.26, Ptrend = 0.62; Phet = 0.04). n-6 PUFAs were suggestively inversely associated with CD8high but not CD8low cancers (CD8high ORT3 vs T1 = 0.61, 95% CI 0.32–1.14, Ptrend = 0.11; CD8low ORT3 vs T1 = 1.63, 95% CI 0.87–3.04, Ptrend = 0.12; Phet = 0.02). Trans fatty acids were positively associated with FAShigh but not FASlow tumors (FAShigh ORT3 vs T1 = 2.94, 95% CI 1.46–5.91, Ptrend = 0.002; FASlow ORT3 vs T1 = 0.99, 95% CI 0.52–1.92, Ptrend = 0.97; Phet = 0.01).

Conclusion
Results indicate that the effects of n-3 PUFAs, n-6 PUFAs, and trans fatty acids on breast cancer risk may vary by tumor tissue expression subtypes. Findings suggest potential immuno-modulatory and FAS-mediated mechanisms.
Producing polished prokaryotic pangenomes with the Panaroo pipeline
Authors: Tonkin-Hill Gerry , MacAlasdair Neil , Ruis Christopher , Weimann Aaron , Horesh Gal , Lees John A. , Gladstone Rebecca A. , Lo Stephanie , Beaudoin Christopher , Floto R. Andres , Frost Simon D.W. , Corander Jukka , Bentley Stephen D. , Parkhill Julian 
Published: July 2020

AbstractPopulation-level comparisons of prokaryotic genomes must take into account the substantial differences in gene content resulting from horizontal gene transfer, gene duplication and gene loss. However, the automated annotation of prokaryotic genomes is imperfect, and errors due to fragmented assemblies, contamination, diverse gene families and mis-assemblies accumulate over the population, leading to profound consequences when analysing the set of all genes found in a species. Here, we introduce Panaroo, a graph-based pangenome clustering tool that is able to account for many of the sources of error introduced during the annotation of prokaryotic genome assemblies. Panaroo is available at https://github.com/gtonkinhill/panaroo.
Identification and genotyping of Enterocytozoon bieneusi in wild Himalayan marmots (Marmota himalayana) and Alashan ground squirrels (Spermophilus alashanicus) in the Qinghai-Tibetan Plateau area (QTPA) of Gansu Province, China
Authors: Xu Jie , Wang Xin , Jing Huaiqi , Cao Shengkui , Zhang Xiaofan , Jiang Yanyan , Yin Jianhai , Cao Jianping , Shen Yujuan 
Published: July 2020

AbstractBackgroundEnterocytozoon bieneusiis the most frequently detected microsporidian species in humans and animals. Currently, to the best of our knowledge, no information onE. bieneusiinfection in Himalayan marmots (Marmota himalayana) and Alashan ground squirrels (Spermophilus alashanicus) is available worldwide. The aim of the present study was to understand the occurrence and genetic characterizations ofE. bieneusiin Himalayan marmots and Alashan ground squirrels in the Qinghai-Tibetan Plateau area (QTPA), Gansu Province, China.MethodsA total of 498 intestinal contents were collected from 399 Himalayan marmots and 99 Alashan ground squirrels in QTPA. These samples were screened for the presence ofE. bieneusiby using nested polymerase chain reaction and sequencing of the internal transcribed spacer (ITS) region of the ribosomal RNA (rRNA) gene. The ITS-positive sequences were aligned and phylogenetically analyzed to determine the genotypes ofE. bieneusi.ResultsThe average infection rate ofE. bieneusiwas 10.0% (50/498), with 11.8% (47/399) in Himalayan marmots and 3.0% (3/99) in Alashan ground squirrels. A total of 7 distinctE. bieneusigenotypes were confirmed: 1 known genotype, YAK1 (n = 18) and 6 novel genotypes, named as ZY37 (n = 27), HN39 (n = 1), HN96 (n = 1), SN45 (n = 1), XH47 (n = 1) and ZY83 (n = 1). All the genotypes obtained in the present study were classified into group 1.ConclusionsTo our knowledge, this is the first report ofE. bieneusiin Himalayan marmots and Alashan ground squirrels in China. The identification of genotype YAK1 in the two rodent species expanded the host range of this genotype. All the seven genotypes were clustered into zoonotic group 1, suggesting that these animal species can be potential epidemiological vectors of zoonotic microsporidiosis caused byE. bieneusiand pose a threat to ecological security. It is necessary to strengthen management practices and surveillance in the investigated areas to reduce the risk ofE. bieneusiinfection from the two rodent species to humans.
High insecticide resistances levels in Anopheles gambiaes s.l. in northern Uganda and its relevance for future malaria control
Authors: Echodu Richard , Iga Julius , Oyet William Samuel , Mireji Paul , Anena Juliet , Onanyang David , Iwiru Tereza , Lutwama Julius Julian , Opiyo Elizabeth Auma 
Published: July 2020

AbstractObjectiveThe aim of the study was to determine the level of insecticide resistance and diversity inAnopheles mosquitoes in northern Uganda. Standard WHO insecticide susceptibility test assays were used to test for susceptibility to 0.5% malathion, 0.1% bendiocarb, 0.05% deltamethrin and 0.75% permethrin on 3–5 day old generation one progeny. We also screened for species diversity and knockdown resistance using PCR assay.ResultsAnopheles gambiae s.s.is the predominant malaria vector in northern Uganda followed byAn. arabiensis. An. gambiaes.s.was susceptible to malathion and bendiocarb with the observed mortality rate of 100% and 98–100% observed respectively while very high resistance was observed with deltamethrin and permethrin. Minimal KDR-eastern variant homozygous forms of 8.3% inAn. gambiae s.s.were detected in Oyam district. In conclusion, this study confirms thatAn. gambiae s.s.females are susceptible to malathion and bendiocarb while high intensity of resistance was observed with deltamethrin and permethrin in the same area. Use of carbamate and organophosphate insecticides bendiocarb and malathion for indoor residual spraying activities in northern Uganda is highly recommended since high levels of pyrethroids resistance (deltamethrin and permethrin) was detected in the area.
Molecular comparison of pure ovarian fibroma with serous benign ovarian tumours
Authors: Hunter Sally M. , Dall Genevieve V. , Doyle Maria A. , Lupat Richard , Li Jason , Allan Prue , Rowley Simone M. , Bowtell David ,   On behalf of AOCS, Campbell Ian G. , Gorringe Kylie L. 
Published: July 2020

Abstract
Objective
Ovarian fibromas and adenofibromas are rare ovarian tumours. They are benign tumours composed of spindle-like stromal cells (pure fibroma) or a mixture of fibroblast and epithelial components (adenofibroma). We have previously shown that 40% of benign serous ovarian tumours are likely primary fibromas due to the neoplastic alterations being restricted to the stromal compartment of these tumours. We further explore this finding by comparing benign serous tumours to pure fibromas.

Results
Performing copy number aberration (CNA) analysis on the stromal component of 45 benign serous tumours and 8 pure fibromas, we have again shown that trisomy of chromosome 12 is the most common aberration in ovarian fibromas. CNAs were more frequent in the pure fibromas than the benign serous tumours (88% vs 33%), however pure fibromas more frequently harboured more than one CNA event compared with benign serous tumours. As these extra CNA events observed in the pure fibromas were unique to this subset our data indicates a unique tumour evolution. Gene expression analysis on the two cohorts was unable to show gene expression changes that differed based on tumour subtype. Exome analysis did not reveal any recurrently mutated genes.
The clinical, immunological and genetic features of 12 Chinese patients with STAT3 mutations
Authors: Lin Li , Wang Ying , Sun Bijun , Liu Luyao , Ying Wenjing , Wang Wenjie , Zhou Qinhua , Hou Jia , Yao Haili , Hu Liyuan , Sun Jinqiao , Wang Xiaochuan 
Published: July 2020

Abstract
Background
Loss-of-function (LOF) mutations in signal transducer and activator of transcription 3 (STAT3) is one of the causes of STAT3 hyperimmunoglobulin E (IgE) syndrome (STAT3-HIES), while gain-of-function (GOF) mutations in STAT3 lead to immune dysregulation diseases. We retrospectively analyzed the age, common clinical symptoms, immunologic and molecular manifestations in 11 patients with LOF STAT3 mutations and 1 patient with a GOF STAT3 mutation.

Methods
Twelve patients were enrolled in our study. Serum immunoglobulin measurements, lymphocyte subset detection and whole-exome sequencing were performed.

Results
The median age at diagnosis of STAT3-HIES patients was 4.74 years. Eczema, recurrent respiratory infections, fevers, abscesses and Staphylococcus aureus infections were the classic manifestations. Elevated serum IgE levels are not always observed in conjunction with high eosinophil counts. A moderate viral DNA load was also measured in peripheral blood mononuclear cells. We noticed that c. 1144C>T was the most common mutation site, followed by c.1311C>A. Additionally, c.1311C>A and c. 1826G>C are two novel mutations. Eight patients achieved notable improvement after receiving intravenous immunoglobulin.

Conclusion
We updated the current knowledge of this topic. We found an earlier median age at diagnosis, a higher survival rate, and a general lack of nonimmunological abnormalities; we also described the treatment details and novel mutations involve in STAT3-HIES and compared STAT3 LOF and GOF mutations.
Progress in studies of epidermal stem cells and their application in skin tissue engineering
Authors: Yang Ronghua , Yang Shuai , Zhao Jingling , Hu Ximin , Chen Xiaodong , Wang Jingru , Xie Julin , Xiong Kun 
Published: July 2020

AbstractThe epidermis, which is the outermost layer of mammalian skin, provides an essential barrier that is essential for maintenance of life. The epidermis is a stratified epithelium, which is maintained by the proliferation of epidermal stem cells (EPSCs) at the basal layer of the epidermis. As a unique cell population characterized by self-renewal and differentiation capabilities, EPSCs ensure the maintenance of adult skin homeostasis and participate in repair of the epidermis after injury. Recently, the utilization of EPSCs for wound healing and tissue regeneration has been attracting increased attention from researchers. In addition, the advances in tissue engineering have increased the interest in applying EPSCs in tissue-engineered scaffolds to further reconstitute injured tissues. In this review, we introduce research developments related to EPSCs, including methods recently used in the culture and enrichment of EPSCs, as well as advanced tools to study EPSCs. The function and mechanism of the EPSC-dermal units in the development and homeostasis of the skin are also summarized. Finally, the potential applications of EPSCs in skin tissue engineering are discussed.
METTL1-mediated m7G methylation maintains pluripotency in human stem cells and limits mesoderm differentiation and vascular development
Authors: Deng Yujie , Zhou Zhongyang , Ji Weidong , Lin Shuibin , Wang Min 
Published: July 2020

Abstract
Background
7-Methylguanosine (m7G) is one of the most conserved modifications in nucleosides within tRNAs and rRNAs. It plays essential roles in the regulation of mRNA export, splicing, and translation. Recent studies highlighted the importance of METTL1-mediated m7G tRNA methylome in the self-renewal of mouse embryonic stem cells (mESCs) through its ability to regulate mRNA translation. However, the exact mechanisms by which METTL1 regulates pluripotency and differentiation in human induced pluripotent stem cells (hiPSCs) remain unknown. In this study, we evaluated the functions and underlying molecular mechanisms of METTL1 in regulating hiPSC self-renewal and differentiation in vivo and in vitro.

Methods
By establishing METTL1 knockdown (KD) hiPSCs, gene expression profiling was performed by RNA sequencing followed by pathway analyses. Anti-m7G northwestern assay was used to identify m7G modifications in tRNAs and mRNAs. Polysome profiling was used to assess the translation efficiency of the major pluripotent transcription factors. Moreover, the in vitro and in vivo differentiation capacities of METTL1-KD hiPSCs were assessed in embryoid body (EB) formation and teratoma formation assays.

Results
METTL1 silencing resulted in alterations in the global m7G profile in hiPSCs and reduced the translational efficiency of stem cell marker genes. METTL1-KD hiPSCs exhibited reduced pluripotency with slower cell cycling. Moreover, METTL1 silencing accelerates hiPSC differentiation into EBs and promotes the expression of mesoderm-related genes. Similarly, METTL1 knockdown enhances teratoma formation and mesoderm differentiation in vivo by promoting cell proliferation and angiogenesis in nude mice.

Conclusion
Our findings provided novel insight into the critical role of METTL1-mediated m7G modification in the regulation of hiPSC pluripotency and differentiation, as well as its potential roles in vascular development and the treatment of vascular diseases.
Therapeutic applications of adipose cell-free derivatives: a review
Authors: Cai Yuan , Li Jianyi , Jia Changsha , He Yunfan , Deng Chengliang 
Published: July 2020

Abstract
Background
Adipose-derived stem cells (ADSCs) have become one of the most utilized adult stem cells due to their abundance and accessibility. Recent studies have shown that paracrine cytokines, exosomes, and other active substances are the main factors through which ADSCs exert their biological effects.

Main body
Adipose cell-free derivatives have been recently gaining attention as potential therapeutic agents for various human diseases. These derivatives include ADSC-conditioned medium (ADSC-CM), ADSC exosomes (ADSC-Exo), and cell-free adipose tissue extracts (ATEs), all of which can be conveniently carried, stored, and transported. Currently, research on ADSC-conditioned medium (ADSC-CM) and ADSC exosomes (ADSC-Exo) is surging. Moreover, cell-free adipose tissue extracts (ATEs), obtained by purely physical methods, have emerged as the focus of research in recent years.

Conclusion
Adipose cell-free derivatives delivery can promote cell proliferation, migration, and angiogenesis, suppress cell apoptosis, and inflammation, as well as reduce oxidative stress and immune regulation. Thus, adipose cell-free derivatives have a broad therapeutic potential in many areas, as they possess anti-skin aging properties, promote wound healing, reduce scar formation, and provide myocardial protection and neuroprotection. This article summarizes these effects and reviews research progress in the use of adipose cell-free derivatives.
rMSIcleanup: an open-source tool for matrix-related peak annotation in mass spectrometry imaging and its application to silver-assisted laser desorption/ionization
Authors: Baquer Gerard , Sementé Lluc , García-Altares María , Lee Young Jin , Chaurand Pierre , Correig Xavier , Ràfols Pere 
Published: July 2020

AbstractMass spectrometry imaging (MSI) has become a mature, widespread analytical technique to perform non-targeted spatial metabolomics. However, the compounds used to promote desorption and ionization of the analyte during acquisition cause spectral interferences in the low mass range that hinder downstream data processing in metabolomics applications. Thus, it is advisable to annotate and remove matrix-related peaks to reduce the number of redundant and non-biologically-relevant variables in the dataset. We have developed rMSIcleanup, an open-source R package to annotate and remove signals from the matrix, according to the matrix chemical composition and the spatial distribution of its ions. To validate the annotation method, rMSIcleanup was challenged with several images acquired using silver-assisted laser desorption ionization MSI (AgLDI MSI). The algorithm was able to correctly classify m/z signals related to silver clusters. Visual exploration of the data using Principal Component Analysis (PCA) demonstrated that annotation and removal of matrix-related signals improved spectral data post-processing. The results highlight the need for including matrix-related peak annotation tools such as rMSIcleanup in MSI workflows.
Majorization inequalities via Green functions and Fink’s identity with applications to Shannon entropy
Authors: Siddique Nouman , Imran Muhammad , Khan Khuram Ali , Pečarić Josip 
Published: July 2020

AbstractThis paper is devoted to obtain generalized results related to majorization-type inequalities by using well-known Fink’s identity and new types of Green functions, introduced by Mehmood et al. (J. Inequal. Appl. 2017:108, 2017). We give a generalized majorization theorem for the class ofn-convex functions. We utilize the Csiszárf-divergence and generalized majorization-type inequalities in providing the corresponding generalizations. As an application, we present the obtained results in terms of Shannon entropy and Kullback–Leibler distance.