bluuebunny/crossref_metadata_2025_split huggingface dataset:
Multiomics profiling of primary lung cancers and distant metastases reveals immunosuppression as a common characteristic of tumor cells with metastatic plasticity
Authors: Lee Won-Chul , Reuben Alexandre , Hu Xin , McGranahan Nicholas , Chen Runzhe , Jalali Ali , Negrao Marcelo V. , Hubert Shawna M. , Tang Chad , Wu Chia-Chin , Lucas Anthony San , Roh Whijae , Suda Kenichi , Kim Jihye , Tan Aik-Choon , Peng David H. , Lu Wei , Tang Ximing , Chow Chi-Wan , Fujimoto Junya , Behrens Carmen , Kalhor Neda , Fukumura Kazutaka , Coyle Marcus , Thornton Rebecca , Gumbs Curtis , Li Jun , Wu Chang-Jiun , Little Latasha , Roarty Emily , Song Xingzhi , Lee J. Jack , Sulman Erik P. , Rao Ganesh , Swisher Stephen , Diao Lixia , Wang Jing , Heymach John V. , Huse Jason T. , Scheet Paul , Wistuba Ignacio I. , Gibbons Don L. , Futreal P. Andrew , Zhang Jianhua , Gomez Daniel , Zhang Jianjun 
Published: November 2020

Abstract

Background
Metastasis is the primary cause of cancer mortality accounting for 90% of cancer deaths. Our understanding of the molecular mechanisms driving metastasis is rudimentary.

Results
We perform whole exome sequencing (WES), RNA sequencing, methylation microarray, and immunohistochemistry (IHC) on 8 pairs of non-small cell lung cancer (NSCLC) primary tumors and matched distant metastases. Furthermore, we analyze published WES data from 35 primary NSCLC and metastasis pairs, and transcriptomic data from 4 autopsy cases with metastatic NSCLC and one metastatic lung cancer mouse model. The majority of somatic mutations are shared between primary tumors and paired distant metastases although mutational signatures suggest different mutagenesis processes in play before and after metastatic spread. Subclonal analysis reveals evidence of monoclonal seeding in 41 of 42 patients. Pathway analysis of transcriptomic data reveals that downregulated pathways in metastases are mainly immune-related. Further deconvolution analysis reveals significantly lower infiltration of various immune cell types in metastases with the exception of CD4+ T cells and M2 macrophages. These results are in line with lower densities of immune cells and higher CD4/CD8 ratios in metastases shown by IHC. Analysis of transcriptomic data from autopsy cases and animal models confirms that immunosuppression is also present in extracranial metastases. Significantly higher somatic copy number aberration and allelic imbalance burdens are identified in metastases.

Conclusions
Metastasis is a molecularly late event, and immunosuppression driven by different molecular events, including somatic copy number aberration, may be a common characteristic of tumors with metastatic plasticity.
Changes in DNA methylation profiles of myalgic encephalomyelitis/chronic fatigue syndrome patients reflect systemic dysfunctions
Authors: Helliwell A. M. , Sweetman E. C. , Stockwell P. A. , Edgar C. D. , Chatterjee A. , Tate W. P. 
Published: November 2020

Abstract

Background
Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a lifelong debilitating disease with a complex pathology not yet clearly defined. Susceptibility to ME/CFS involves genetic predisposition and exposure to environmental factors, suggesting an epigenetic association. Epigenetic studies with other ME/CFS cohorts have used array-based technology to identify differentially methylated individual sites. Changes in RNA quantities and protein abundance have been documented in our previous investigations with the same ME/CFS cohort used for this study.

Results
DNA from a well-characterised New Zealand cohort of 10 ME/CFS patients and 10 age-/sex-matched healthy controls was isolated from peripheral blood mononuclear (PBMC) cells, and used to generate reduced genome-scale DNA methylation maps using reduced representation bisulphite sequencing (RRBS). The sequencing data were analysed utilising the DMAP analysis pipeline to identify differentially methylated fragments, and the MethylKit pipeline was used to quantify methylation differences at individual CpG sites. DMAP identified 76 differentially methylated fragments and Methylkit identified 394 differentially methylated cytosines that included both hyper- and hypo-methylation. Four clusters were identified where differentially methylated DNA fragments overlapped with or were within close proximity to multiple differentially methylated individual cytosines. These clusters identified regulatory regions for 17 protein encoding genes related to metabolic and immune activity. Analysis of differentially methylated gene bodies (exons/introns) identified 122 unique genes. Comparison with other studies on PBMCs from ME/CFS patients and controls with array technology showed 59% of the genes identified in this study were also found in one or more of these studies. Functional pathway enrichment analysis identified 30 associated pathways. These included immune, metabolic and neurological-related functions differentially regulated in ME/CFS patients compared to the matched healthy controls.

Conclusions
Major differences were identified in the DNA methylation patterns of ME/CFS patients that clearly distinguished them from the healthy controls. Over half found in gene bodies with RRBS in this study had been identified in other ME/CFS studies using the same cells but with array technology. Within the enriched functional immune, metabolic and neurological pathways, a number of enriched neurotransmitter and neuropeptide reactome pathways highlighted a disturbed neurological pathophysiology within the patient group.
APOE4 is associated with cognitive and pathological heterogeneity in patients with Alzheimer’s disease: a systematic review
Authors: Emrani Sheina , Arain Hirra A. , DeMarshall Cassandra , Nuriel Tal 
Published: November 2020

Abstract
Possession of the ε4 allele of apolipoprotein E (APOE) is the primary genetic risk factor for the sporadic form of Alzheimer’s disease (AD). While researchers have extensively characterized the impact that APOE ε4 (APOE4) has on the susceptibility of AD, far fewer studies have investigated the phenotypic differences of patients with AD who are APOE4 carriers vs. those who are non-carriers. In order to understand these differences, we performed a qualitative systematic literature review of the reported cognitive and pathological differences between APOE4-positive (APOE4+) vs. APOE4-negative (APOE4−) AD patients. The studies performed on this topic to date suggest that APOE4 is not only an important mediator of AD susceptibility, but that it likely confers specific phenotypic heterogeneity in AD presentation, as well. Specifically, APOE4+ AD patients appear to possess more tau accumulation and brain atrophy in the medial temporal lobe, resulting in greater memory impairment, compared to APOE4− AD patients. On the other hand, APOE4− AD patients appear to possess more tau accumulation and brain atrophy in the frontal and parietal lobes, resulting in greater impairment in executive function, visuospatial abilities, and language, compared to APOE4+ AD patients. Although more work is necessary to validate and interrogate these findings, these initial observations of pathological and cognitive heterogeneity between APOE4+ vs. APOE4− AD patients suggest that there is a fundamental divergence in AD manifestation related to APOE genotype, which may have important implications in regard to the therapeutic treatment of these two patient populations.
Ca2+-activated mitochondrial biogenesis and functions improve stem cell fate in Rg3-treated human mesenchymal stem cells
Authors: Hong Taeui , Kim Moon Young , Da Ly Dat , Park Su Jung , Eom Young Woo , Park Kyu-Sang , Baik Soon Koo 
Published: November 2020

Abstract
Although mitochondrial functions are essential for cell survival, their critical roles in stem cell fate, including proliferation, differentiation, and senescence, remain elusive. Ginsenoside Rg3 exhibits various biological activities and reportedly increases mitochondrial biogenesis and respiration. Herein, we observed that Rg3 increased proliferation and suppressed senescence of human bone marrow-derived mesenchymal stem cells. Osteogenic, but not adipogenic, differentiation was facilitated by Rg3 treatment. Rg3 suppressed reactive oxygen species production and upregulated mitochondrial biogenesis and antioxidant enzymes, including superoxide dismutase. Consistently, Rg3 strongly augmented basal and ATP synthesis-linked respiration with high spare respiratory capacity. Rg3 treatment elevated cytosolic Ca2+ concentration contributing to mitochondrial activation. Reduction of intracellular or extracellular Ca2+ levels strongly inhibited Rg3-induced activation of mitochondrial respiration and biogenesis. Taken together, Rg3 enhances capabilities of mitochondrial and antioxidant functions mainly through a Ca2+-dependent pathway, which improves the proliferation and differentiation potentials and prevents the senescence of human mesenchymal stem cells.
The in vitro efficacy of eye drops containing a bacteriophage solution specific for Staphylococcus spp. isolated from dogs with bacterial conjunctivitis
Authors: Urban-Chmiel Renata , Balicki Ireneusz , Świąder Katarzyna , Nowaczek Anna , Pyzik Ewelina , Stępień-Pyśniak Dagmara , Marek Agnieszka , Puchalski Andrzej , Wernicki Andrzej , Poleszak Ewa , Dec Marta 
Published: November 2020

Abstract

Background
The purpose of the study was to evaluate the in vitro antibacterial effect of experimental eye drops with bacteriophages in elimination of Staphylococcus spp. isolated from dogs with bacterial conjunctivitis.. The bacterial material was collected from dogs with independent clinical signs of bacterial conjunctivitis. Staphylococcus spp. were identified by phenotypic and genotypic methods (MALDI-TOF MS mass spectrometry). Antibiotic resistance was determined by the disc-diffusion method. Phage activity (Plaque forming units, PFU) was determined on double-layer agar plates. Phages with lytic titres > 108 PFU were used to prepare eye drops. The stability of the antibacterial titre was evaluated for preparations stored in sealed bottles as well as after opening and reclosing.

Results
The tests confirmed the occurrence of Staphylococcus spp. strains as etiological agents of bacterial conjunctivitis in dogs. A high percentage of strains were resistant to more than three antibiotics. The experimental phage eye drops used in the study exhibited 100% efficacy in vitro against the tested Staphylococcus isolates. Particularly noteworthy is the long duration of activity and constant antibacterial lytic titre of ≥108 PFU/mL of two eye drop solutions, nos. 7 and 12, after the bottle had been opened (21 days) and after hermetically sealed packaging (28 days) at 4–8 °C.

Conclusions
The results represent the first stage of research and require continuation in vivo. If positive effects are obtained in animals, the results can be used in applied research in humans and animals.
A note on Nakano generalized difference sequence space
Authors: Bakery Awad A. , Elmatty Afaf R. Abou 
Published: November 2020

Abstract
In this paper, we investigate the necessary conditions on any s-type sequence space to form an operator ideal. As a result, we show that the s-type Nakano generalized difference sequence space X fails to generate an operator ideal. We investigate the sufficient conditions on X to be premodular Banach special space of sequences and the constructed prequasi-operator ideal becomes a small, simple, and closed Banach space and has eigenvalues identical with its s-numbers. Finally, we introduce necessary and sufficient conditions on X explaining some topological and geometrical structures of the multiplication operator defined on X.
A decade of antimicrobial resistance research in social science fields: a scientometric review
Authors: Lu Jiahui , Sheldenkar Anita , Lwin May Oo 
Published: November 2020

Abstract

Background
Though social sciences are expectedly instrumental in combating antimicrobial resistance (AMR), their research on AMR has been historically lacking.

Objectives
This study aims to understand the current academic literature on AMR within the social science field by investigating international contributions, emerging topics, influential articles, and prominent outlets, to identify research gaps and future directions.

Methods
Bibliometric data of 787 peer-reviewed journal articles published in the period of 2010 to 2019 were extracted from the Social Science Citation Index in the Web of Science database. Bibliographic networks of the extracted articles were examined.

Results
Social science research on AMR has grown rapidly in the past 5 years. While western developed countries contributed the most to the field in the past decade, research within developing regions such as Asia and Africa have increased in the last 2 years. Social sciences have been contributing to AMR research in several different domains from surveillance and risk assessment of AMR, to promotions of appropriate use of antimicrobials in primary care and clinical settings. Though the idea of one health has been incorporated into research on AMR within the medical and microbial science fields, it has not been well recognized by social sciences.

Conclusion
Social science research on AMR is a new, while rapidly developing, research area that requires continued and intense global efforts from an interdisciplinary and one health approach. Research on social issues surrounding AMR transmissions between human, animal, and environments should be emphasized in the future.
Assessment of geographical origin and production period of royal jelly by NMR metabolomics
Authors: Mazzei Pierluigi , Piccolo Alessandro , Brescia Marianna , Caprio Emilio 
Published: November 2020

AbstractBackgroundRoyal jelly (RJ) represents the most valuable product of beekeeping activities. The illegal introduction of RJ of uncertain quality/origin in European agrofood markets is not controlled, since the conventional analytical methods cannot unambiguously distinguish foreign from autochthonous RJ products. Here, we applied liquid-state NMR spectroscopy combined with chemometry to characterize the metabolic profile of representative Italian high-quality RJ products and evaluate the discrimination capacity of this analytical technique.Materials and methodsRJ samples were supplied by an Italian consortium of royal jellies producers and developed in the period May–July 2016. Samples were dissolved in a deuterated water solution brought at pH 7.3 and analysed through high resolution liquid-state NMR spectroscopy. 1D and 2D homo- and heteronuclear experiments were acquired to identify the RJ metabolomics profile. Proton NMR spectra were elaborated to conduct an NMR-based metabolomic approach based on PCA and DA chemometric analyses.ResultsThe NMR-based metabolomics precisely and significantly (pvalue < 0.05, according to Benjamini-Hochberg’s test) authenticated the RJ products, by reliably tracing both their geographical and botanical origin, as well as their production period. In particular, Chinese RJ products exhibited a larger amount of citrate and lysine, accompanied by a lower content of 10-HDA. Our results showed that NMR spectroscopy can recognize low-quality fraudulent products and become an useful analytical tool to certify and trace the RJ molecular composition.ConclusionsThe application of NMR spectroscopy promises to enable the efficient protection of both the producers and consumers of high-quality royal jelly. In addition, the proposed method may be used in combination with the conventional melissopalynological methods for recognizing frauds.
Prevalence and factors associated with neonatal hypoglycemia in Northern Uganda: a community-based cross-sectional study
Authors: Mukunya David , Odongkara Beatrice , Piloya Thereza , Nankabirwa Victoria , Achora Vincentina , Batte Charles , Ditai James , Tylleskar Thorkild , Ndeezi Grace , Kiguli Sarah , Tumwine James K. 
Published: November 2020

Abstract

Background
Neonatal hypoglycemia is the most common endocrine abnormality in children, which is associated with increased morbidity and mortality. The burden and risk factors of neonatal hypoglycemia in rural communities in sub-Saharan Africa are unknown.

Objective
To determine the prevalence and risk factors for neonatal hypoglycemia in Lira District, Northern Uganda.

Methods
This was a community-based cross-sectional study, nested in a cluster randomized controlled trial designed to promote health facility births and newborn care practices in Lira District, Northern Uganda. This study recruited neonates born to mothers in the parent study. Random blood glucose was measured using an On Call® Plus glucometer (ACON Laboratories, Inc., 10125 Mesa Road, San Diego, CA, USA). We defined hypoglycemia as a blood glucose of < 47 mg/dl. To determine the factors associated with neonatal hypoglycemia, a multivariable linear regression mixed-effects model was used.

Results
We examined 1416 participants of mean age 3.1 days (standard deviation (SD) 2.1) and mean weight of 3.2 kg (SD 0.5). The mean neonatal blood glucose level was 81.6 mg/dl (SD 16.8). The prevalence of a blood glucose concentration of < 47 mg/dl was 2.2% (31/1416): 95% CI 1.2%, 3.9%. The risk factors for neonatal hypoglycemia were delayed breastfeeding initiation [adjusted mean difference, − 2.6; 95% CI, − 4.4, − 0.79] and child age of 3 days or less [adjusted mean, − 12.2; 95% CI, − 14.0, − 10.4].

Conclusion
The incidence of neonatal hypoglycemia was low in this community and was predicted by delay in initiating breastfeeding and a child age of 3 days or less. We therefore suggest targeted screening and management of neonatal hypoglycemia among neonates before 3 days of age and those who are delayed in the onset of breastfeeding.
Performance evaluation of the novel portable PIMA point-of-care CD4 analyzer in comparison with conventional flow cytometer instruments in Cameroon
Authors: Sagnia Bertrand , Kamgaing Rachel , Kouanfack Charles , Kamdem Georgette , Sosso Samuel , Temgoua Edith , Tsomo Zéphyrin , Mabouli Zoa Lucille , Tangimpundu Charlotte , Nchinda Godwin , Ndjolo Alexis 
Published: November 2020

Abstract

Background
Absolute CD4+ T-lymphocyte counts are used in the initiation and monitoring of antiretroviral therapy in HIV-infected patients: with the increase number of HIV infected patient and the reduce number of heath care system in rural zones, HIV monitoring in resource-constrained settings demands affordable and reliable CD4+ T lymphocytes enumeration methods. We evaluated a simple PIMA POC which is a dedicated system for enumeration that uses immunomagnetic and immunofluorescent technologies. The instrument was designed to be a low-cost, yet reliable and robust one. In this study, we assessed the correlation between most representative flow cytometry instruments present in Cameroon instead of CyFlow from PARTEC, FACSCount, and FACSCalibur both from Becton Dickinson.

Methods
CD4 surface markers on lymphocytes was measured on samples collected in EDTA tubes from 268 patients aged from 1 to 65 years old in three different health care structures. HIV infected patients are coming from CIRCB, Day Hospital of Hopital Central de Yaounde (HCY) and Hopital General de Yaounde (HGY). After inform consent, samples were collected and 101 samples were tested with the FACSCalibur, 60 samples were tested with the CyFlow and 107 samples were tested with the FACSCount flow cytometers. All these samples were tested by different technician with PIMA POC present in all these health care structures and the correlation and agreement were analyzed using linear regression and Bland–Altman analysis.

Results
The PIMA POC system has excellent precision, accuracy and linearity for CD4+ T lymphocytes enumeration. Good correlations were obtained between the PIMA POC system and other single platform methods. Bland–Altman plots showed interchangeability between the three machines. Absolute CD4+ T-lymphocyte values obtained from the PIMA system correlated well with Cyflow, FACSCount, and FACSCalibur method (r2 varies from 0.88 to 0.968, P < 0.0001). The comparison between values obtained from PIMA with CYFLOW, FACSCount, and FACSCalibur give P = 0.17, P = 0.5 and P = 0.6 respectively meaning that there is not significant differences between values obtained with PIMA and other flow machines.

Conclusion
This POC PIMA system is a simple and reliable system for enumeration of absolute CD4+ T-lymphocytes. Having one PIMA system easy to use, should reduce the cost and thus increase access to CD4 testing for HIV infected patients in resource-constrained countries. POC CD4 may also alleviate testing burdens at traditional central CD4 laboratories, hence improving test access in both rural and urban environments. This will reduce also the loss of follow up.
Outcome predictors of intravenous thrombolytic therapy in acute ischemic stroke patients: an Egyptian center experiences
Authors: Tork Mohamed A. , Aref Hany M. , El-Khawas Hala M. , Khalil Mohamed F. , ElSadek Ahmed 
Published: November 2020

AbstractBackgroundIntravenous thrombolytic therapy remains the guideline-recommended treatment to improve outcomes after acute ischemic stroke. However, the functional outcome among patients with acute ischemic stroke after receiving intravenous thrombolytic therapy is influenced by huge variety of factors, and this was the aim of our study to evaluate the outcome predictors of intravenous thrombolytic therapy in a sample of Egyptian patients with acute ischemic stroke.MethodsWe enrolled 183 acute ischemic stroke patients who were treated with intravenous recombinant tissue plasminogen activator (IV rtPA) according to the last updated guidelines of American Heart Association and American Stroke Association (AHA/ASA) from February 2018 to February 2020; however, only 150 patients of them completed our study plan till the end. Data of study variables were collected, analyzed statistically and correlated with the functional outcome 3 months after receiving IV rtPA using the modified Rankin Scale (mRS).ResultsGood functional outcome was seen in 98 (65.3%) patients and poor functional outcome was seen in 52 (34.7%) patients. Multivariate analysis of the study variables was done to detect the significant independent predictors of the functional outcome. Atrial fibrillation (AF) (Pvalue < 0.001*OR 6.28*(95% C.I)), hypertension (Pvalue 0.001*OR 3.65*(95% C.I)), diabetes mellitus (DM) (Pvalue 0.009*OR 2.805*(95% C.I)), increased National Institute of Health Stroke Scale (NIHSS) score 24 h after receiving IV rtPA (Pvalue 0.003*OR 8.039*(95% C.I)), increased pulsatility index (PI) value in cerebral vessels at the same side of stroke lesion (Pvalue 0.038*OR 42.48*(95% C.I)) were the significant independent predictors of poor functional outcome. On the other hand decreased NIHSS score 24 h after receiving IV rtPA (Pvalue 0.003*OR 0.124*(95% C.I)), Normal value of PI in cerebral vessels at the same side of stroke lesion (Pvalue 0.038*OR 42.48*(95% C.I)) were the significant independent predictors of good functional outcome.ConclusionIntravenous thrombolytic therapy improves the functional outcome of acute ischemic stroke patients. Also, AF, hypertension, DM, NIHSS 24 h after receiving IV rtPA and PI could be used as independent predictors of the functional outcome.
Pain related viral infections: a literature review
Authors: Widyadharma I. Putu Eka , Dewi Putri Rossyana , Wijayanti Ida Ayu Sri , Utami Desak Ketut Indrasari 
Published: November 2020

AbstractPain is a common health problem all around the world. The pain symptoms are various depending on the underlying disease or the direct cause of pain itself. Viral infection could cause arthralgia or acute-onset arthritis, moreover in pandemic era of SARS-CoV-2 infection. The patients might experience arthritis, arthralgia, joint pain, or musculoskeletal pain. Viral infection including parvovirus B19, hepatitis virus, human immunodeficiency virus, arthropod-borne virus, and coronavirus could cause various types of pain. The pathogenesis of these symptoms is similar to each other despite of different causative organism. This review will discuss about pain caused by various causative organisms.