bluuebunny/crossref_metadata_2025_split huggingface dataset:
Phagocyte activity reflects mammalian homeo- and hetero-thermic physiological states
Authors: Pikula Jiri , Heger Tomas , Bandouchova Hana , Kovacova Veronika , Nemcova Monika , Papezikova Ivana , Piacek Vladimir , Zajíčková Renata , Zukal Jan 
Published: July 2020

AbstractBackgroundEmergence of both viral zoonoses from bats and diseases that threaten bat populations has highlighted the necessity for greater insights into the functioning of the bat immune system. Particularly when considering hibernating temperate bat species, it is important to understand the seasonal dynamics associated with immune response. Body temperature is one of the factors that modulates immune functions and defence mechanisms against pathogenic agents in vertebrates. To better understand innate immunity mediated by phagocytes in bats, we measured respiratory burst and haematology and blood chemistry parameters in heterothermic greater mouse-eared bats (Myotis myotis) and noctules (Nyctalus noctula) and homeothermic laboratory mice (Mus musculus).ResultsBats displayed similar electrolyte levels and time-related parameters of phagocyte activity, but differed in blood profile parameters related to metabolism and red blood cell count. Greater mouse-eared bats differed from mice in all phagocyte activity parameters and had the lowest phagocytic activity overall, while noctules had the same quantitative phagocytic values as mice. Homeothermic mice were clustered separately in a high phagocyte activity group, while both heterothermic bat species were mixed in two lower phagocyte activity clusters. Stepwise regression identified glucose, white blood cell count, haemoglobin, total dissolved carbon dioxide and chloride variables as the best predictors of phagocyte activity. White blood cell counts, representing phagocyte numbers available for respiratory burst, were the best predictors of both time-related and quantitative parameters of phagocyte activity. Haemoglobin, as a proxy variable for oxygen available for uptake by phagocytes, was important for the onset of phagocytosis.ConclusionsOur comparative data indicate that phagocyte activity reflects the physiological state and blood metabolic and cellular characteristics of homeothermic and heterothermic mammals. However, further studies elucidating trade-offs between immune defence, seasonal lifestyle physiology, hibernation behaviour, roosting ecology and geographic patterns of immunity of heterothermic bat species will be necessary. An improved understanding of bat immune responses will have positive ramifications for wildlife and conservation medicine.
Clinical evaluation of potential usefulness of serum lactate dehydrogenase (LDH) in 2019 novel coronavirus (COVID-19) pneumonia
Authors: Wu Mei-ying , Yao Lin , Wang Yi , Zhu Xin-yun , Wang Xia-fang , Tang Pei-jun , Chen Cheng 
Published: July 2020

Abstract
Background
There was much evidence suggesting that the serum lactate dehydrogenase (LDH) levels reflect the extent of various pathophysiological processes. However, the current information about dynamic change of LDH in COVID-19 pneumonia has not been well investigated.

Methods
Study was performed in 87 cases confirmed by COVID-19 infection. The serum LDH levels were determined at diagnosis and follow-up visits. The evaluation of clinical response to therapy was based on chest CT scan. We selected the value of LDH around the data of chest CT scan (− 1 ~ + 1 day).

Results
At diagnosis, significant differences in LDH levels were found between non-severe and severe group (P < 0.05). It was demonstrated that increase or decrease of LDH was indicative of radiographic progress or improvement (P < 0.05). The time to LDH normalization (5.67 ± 0.55, days) was positively correlated with the time to radiographic absorption (5.57 ± 0.65 days, r = 0.53, P < 0.05). Applying the cut-off value of the increase in LDH has good specificity to predict disease progression.

Conclusions
Serum LDH was validated for its potential usefulness as markers for evaluating clinical severity and monitoring treatment response in COVID-19 pneumonia.
Effect of hypertension on outcomes of adult inpatients with COVID-19 in Wuhan, China: a propensity score–matching analysis
Authors: Yang Qing , Zhou Ying , Wang Xinrong , Gao Shan , Xiao Yang , Zhang Weiming , Hu Yi , Wang Yafei 
Published: July 2020

Abstract
Background
Previous studies have shown that Coronavirus Disease 2019 (COVID-19) patients with underlying comorbidities can have worse outcomes. However, the effect of hypertension on outcomes of COVID-19 patients remains unclear.

Research question
The aim of this study was to explore the effect of hypertension on the outcomes of patients with COVID-19 by using propensity score–matching (PSM) analysis.

Study design and methods
Participants enrolled in this study were patients with COVID-19 who had been hospitalized at the Central Hospital of Wuhan, China. Chronic comorbidities and laboratory and radiological data were reviewed; patient outcomes and lengths of stay were obtained from discharge records. We used the Cox proportional-hazard model (CPHM) to analyze the effect of hypertension on these patients’ outcomes and PSM analysis to further validate the abovementioned effect.

Results
A total of 226 patients with COVID-19 were enrolled in this study, of whom 176 survived and 50 died. The proportion of patients with hypertension among non-survivors was higher than that among survivors (26.70% vs. 74.00%; P < 0.001). Results obtained via CPHM showed that hypertension could increase risk of mortality in COVID-19 patients (hazard ratio 3.317; 95% CI [1.709–6.440]; P < 0.001). Increased D-dimer levels and higher ratio of neutrophils to lymphocytes (N/L) were also found to increase these patients’ mortality risk. After matching on propensity score, we still came to similar conclusions. After we applied the same method in critically ill patients, we found that hypertension also increased risk of death in patients with severe COVID-19.

Conclusion
Hypertension, increased D-dimer and the ratio of neutrophil to lymphocyte increased mortality in patients with COVID-19, with hypertension in particular.
Establishment and validation of a novel nomogram incorporating clinicopathological parameters into the TNM staging system to predict prognosis for stage II colorectal cancer
Authors: Mo Shaobo , Zhou Zheng , Li Yaqi , Hu Xiang , Ma Xiaoji , Zhang Long , Cai Sanjun , Peng Junjie 
Published: July 2020

Abstract
Background
Survival outcomes are significantly different in stage II colorectal cancer (CRC) patients with diverse clinicopathological features. The objective of this study is to establish a credible prognostic nomogram incorporating easily obtained parameters for stage II CRC patients.

Methods
A total of 1708 stage II CRC patients seen at Fudan University Shanghai Cancer Center (FUSCC) from 2008 to 2013 were retrospectively analyzed in this study. Cases were randomly separated into a training set (n = 1084) and a validation set (n = 624). Univariate and multivariate Cox regression analyses were used to identify independent prognostic factors that were subsequently incorporated into a nomogram. The performance of the nomogram was evaluated by the predicted concordance index (C-index) and ROC curve to calculate the area under the curve (AUC). The clinical utility of the nomogram was evaluated using decision curve analysis (DCA).

Results
In univariate and multivariate analyses, eight parameters were correlated with disease-free survival (DFS), which were subsequently selected to generate a prognostic nomogram based on DFS. For DFS predictions, the C-index values of the nomogram were 0.842 (95% confidence interval (CI) 0.710–0.980), and 0.701 (95% CI 0.610–0.770) for the training and validation sets, respectively. The AUC values of the ROC curves for the nomogram to predicted 1, 3 and 5-year survival were 0.869, 0.858, and 0.777 (training group) and 0.673, 0.714, and 0.706 (validation group), respectively. The recurrence probability calibration curve showed good consistency between actual observations and nomogram-based predictions. DCA showed better clinical application value for the nomogram than the TNM staging system.

Conclusion
A novel nomogram was established and validated in a large population, and the nomogram is a simple-to-use tool for physicians to facilitate postoperative personalized prognostic evaluation and determine therapeutic strategies for stage II CRC patients.
The prognostic value of lncRNA SNHG6 in cancer patients
Authors: Shen Haixiang , Mo Qiwang , Xu Xin , Liu Ben 
Published: July 2020

Abstract
Background
Although tremendous improvement has been seen in cancer diagnosis and treatment, its morbidity and mortality is still high due to lack of ideal biomarkers. An increasing number of studies have demonstrated that the expression of lncRNA small nucleolar RNA host gene 6 (SNHG6) has significantly negative correlation with various cancer prognosis. The present meta-analysis was aimed to clarify the potential of clinical application of SNHG6 in cancers.

Methods
A detailed literature review was conducted by searching through PubMed and Web of Science databases. The expression level of SNHG6, clinicopathological features and survival outcomes were extracted from eligible studies. Pooled analysis was performed with a DerSimonian-Laird random-effect model. The results were further validated through the Cancer Genome Atlas (TCGA) dataset.

Results
Five studies with a total of 487 cases were finally included in this meta-analysis. The results demonstrated that a high expression of SNHG6 was significantly associated with an increased risk of poor overall survival (OS) in cancer patients (HR = 2.06, 95% CI 1.56–2.73). Similar results from the TCGA dataset further confirmed our findings.

Conclusions
Overexpressed SNHG6 was significantly associated with poor prognosis in various cancers. Therefore, SNHG6 may become a novel molecular target for treatment and prognostic evaluation.
Potential theranostics of circulating tumor cells and tumor-derived exosomes application in colorectal cancer
Authors: Vafaei Somayeh , Roudi Raheleh , Madjd Zahra , Aref Amir Reza , Ebrahimi Marzieh 
Published: July 2020

Abstract
Background
At the present time, colorectal cancer (CRC) is still known as a disease with a high mortality rate. Theranostics are flawless scenarios that link diagnosis with therapy, including precision medicine as a critical platform that relies on the development of biomarkers particularly “liquid biopsy”. Circulating tumor cells (CTCs) and tumor-derived exosomes (TDEs) in a liquid biopsy approach are of substantial importance in comparison with traditional ones, which cannot generally be performed to determine the dynamics of the tumor due to its wide restriction of range. Thus, recent attempts has shifted towards minimally noninvasive methods.

Main text
CTCs and TDEs, as significant signals emitted from the tumor microenvironment, which are also detectable in the blood, prove themselves to be promising novel biomarkers for cancer diagnosis, prognosis, and treatment response prediction. The therapeutic potential of them is still limited, and studies are at its infancy. One of the major challenges for the implementation of CTCs and TDEs which are new trends in translational medicine is the development of isolation and characterization; a standardizable approach. This review highlights and discusses the current challenges to find the bio fluids application in CRC early detection and clinical management.

Conclusion
Taken together, CTCs and TDEs as silent drivers of metastasis can serve in the management of cancer patient treatment and it is of the upmost importance to expand our insight into this subject. However, due to the limited data available from clinical trials, further validations are required before addressing their putative application in oncology.
CircRNA CDR1as/miR-641/HOXA9 pathway regulated stemness contributes to cisplatin resistance in non-small cell lung cancer (NSCLC)
Authors: Zhao Yongsheng , Zheng Renyan , Chen Jian , Ning Dong 
Published: July 2020

Abstract
Background
Cisplatin (DDP) is the first-line chemotherapeutic drug for non-small cell lung cancer (NSCLC), and long-term DDP stimulation increased resistance of NSCLC cells to this drug by enriching cancer stem cells (CSCs), which contributed to recurrence and worse prognosis of NSCLC, but the molecular mechanisms are still not fully delineated.

Methods
Real-Time qPCR and Western Blot analysis were conducted to examine gene expressions at mRNA and protein levels, respectively. Dual-luciferase reporter gene system was used to validate the targeting sites among circRNA CDR1as, miR-641 and HOXA9 mRNA. Cell growth was evaluated by CCK-8 assay, trypan blue staining assay and colony formation assay. The Annexin V-FITC/PI double staining method was employed to measure cell apoptosis ratio. Spheroid formation and flow cytometer assay was used to evaluate cell stemness. Xenograft mice models were established to measure tumorgenicity in vivo, and Ki67 expressions in mice tumor tissues were examined by immunohistochemistry (IHC).

Results
Here we identified a novel circRNA CDR1as/miR-641/Homeobox protein Hox-A9 (HOXA9) pathway regulated stemness and DDP chemoresistance in NSCLC. Mechanistically, circRNA CDR1as and HOXA9 were high-expressed, while miR-641 was low-expressed in DDP-resistant NSCLC cells, instead of their corresponding parental DDP-sensitive NSCLC cells. Additionally, we validated that circRNA CDR1as positively regulated HOXA9 in NSCLC cells by serving as an RNA sponge for miR-641, and knock-down of circRNA CDR1as increased the sensitivity of DDP-resistant NSCLC cells, which were reversed by downregulating miR-641 and upregulating HOXA9. Consistently, overexpression of circRNA CDR1as increased drug resistance of DDP-sensitive NSCLC cells by regulating miR-641/HOXA9 axis. In addition, the expression levels of stemness signatures (SOX2, OCT4 and Nanog) were higher in DDP-resistant NSCLC cells, which also tended to form spheres and enrich CD44+CD166+ population compared to their parental DDP-sensitive NSCLC cells, suggesting that CSCs were enriched in DDP-resistant NSCLC cells. Notably, knock-down of circRNA CDR1as inhibited stemness of DDP-resistant NSCLC cells by inhibiting HOXA9 through upregulating miR-641.

Conclusions
Taken together, this study identified that circRNA CDR1as regulated stemness and DDP chemoresistance in NSCLC cells by targeting miR-641/HOXA9 axis.
Fluorescent markers rhodamine B and uranine for Anopheles gambiae adults and matings
Authors: Aviles Erica I. , Rotenberry Rachel D. , Collins C. Mathilda , Dotson Ellen. M. , Benedict Mark Q. 
Published: July 2020

Abstract
Background
Marking mosquitoes is vital for mark-release-recapture and many laboratory studies, but their small size precludes the use of methods that are available for larger animals such as unique identifier tags and radio devices. Fluorescent dust is the most commonly used method to distinguish released individuals from the wild population. Numerous colours and combinations can be used, however, dust sometimes affects longevity and behaviour so alternatives that do not have these effects would contribute substantially. Rhodamine B has previously been demonstrated to be useful for marking adult Aedes aegypti males when added to the sugar meal. Unlike dust, this also marked the seminal fluid making it possible to detect matings by marked males in the spermatheca of females. Here, marking of Anopheles gambiae sensu stricto with rhodamine B and uranine was performed to estimate their potential contribution.

Methods
Two fluorescent markers, rhodamine B and uranine, were dissolved in sugar water and fed to adult An. gambiae. Concentrations that are useful for marking individuals and seminal fluid were determined. The effects on adult longevity, the durability of the marking and detection of the marker in mated females was determined. Male mating competitiveness was also evaluated.

Results
Rhodamine B marking in adults is detectable for at least 3 weeks, however uranine marking declines with time and at low doses can be confused with auto-fluorescence. Both can be used for marking seminal fluid which can be detected in females mated by marked males, but, again, at low concentrations uranine-marking is more easily confused with the natural fluorescence of seminal fluid. Neither dye affected mating competitiveness.

Conclusions
Both markers tested could be useful for field and laboratory studies. Their use has substantial potential to contribute to a greater understanding of the bio-ecology of this important malaria vector. Rhodamine B has the advantage that it appears to be permanent and is less easily confused with auto-fluorescence. The primary limitation of both methods is that sugar feeding is necessary for marking and adults must be held for at least 2 nights to ensure all individuals are marked whereas dusts provide immediate and thorough marking.
Defining symptoms of malaria in India in an era of asymptomatic infections
Authors: van Eijk Anna Maria , Mannan Asad S. , Sullivan Steven A. , Carlton Jane M. 
Published: July 2020

Abstract
Background
Malaria is a major public health problem in India. Data from surveys totaling 3031 participants at three sites revealed a high proportion of asymptomatic infections, complicating diagnosis. The aim of this study was to identify differences in complaints and symptoms between sites, and factors associated with asymptomatic Plasmodium infections.

Methods
Published data from community-based cross-sectional studies conducted between 2012 and 2015 in Nadiad (Gujarat), Chennai (Tamil Nadu), and Rourkela (Odisha) as part of the Center for the Study of Complex Malaria in India were analysed. Complaints and symptoms were systematically recorded, and Plasmodium infections confirmed using microscopy, rapid diagnostic tests (RDTs), and polymerase chain reaction (PCR). Multivariate analyses were conducted to determine the association between general symptoms and age, season, or gender, and factors associated with asymptomatic Plasmodium infections were assessed.

Results
Complaints of any illness were lowest in Chennai (17.7%), 30.6% in Rourkela and 42.7% in Nadiad. Complaints were more often reported for children; gender differences were noted in Rourkela only. In Nadiad, 7.0% of 796 participants were positive for malaria by PCR (32% Plasmodium falciparum); 78.6% had a history of fever or documented fever, 14.3% had other symptoms, and 7.1% were “truly asymptomatic”. For Chennai this was 29.2%, 4.2% and 66.7% respectively, with a malaria prevalence of 2.6% by PCR of 928 participants (29% P. falciparum). In Rourkela, with 7.7% of 1307 participants positive for malaria by PCR (82% P. falciparum), the percentages were 35.6%, 24.8% and 39.6%, respectively. In Rourkela, asymptomatic infections were associated with young age and male gender (microscopy or RDT), and with rainy season (PCR). In the same site, participants with Plasmodium vivax were more likely to be asymptomatic (11/18 or 61.1%) than persons with P. falciparum mono-infections (27/78 or 34.6%); gametocytes for P. falciparum were evenly distributed between symptomatic and asymptomatic infections (2/53 vs. 2/49, respectively). The addition of the symptoms “headache”, “aches” and “chills” to fever improved the case-definition of symptomatic malaria.

Conclusion
There were considerable differences in complaints at the three sites in India. Malaria and asymptomatic infections differ by region, indicating that malaria elimination will require localized approaches.
Investigating selected host and parasite factors potentially impacting upon seasonal malaria chemoprevention in Bama, Burkina Faso
Authors: Somé Fabrice A. , Bazié Thomas , Ehrlich Hanna Y. , Goodwin Justin , Lehane Aine , Neya Catherine , Zachari Kabré , Wade Martina , Ouattara Jean-Marie , Foy Brian D. , Dabiré Roch K. , Parikh Sunil , Ouédraogo Jean-Bosco 
Published: July 2020

Abstract
Background
Since 2014, seasonal malaria chemoprevention (SMC) with amodiaquine–sulfadoxine–pyrimethamine (AQ–SP) has been implemented on a large scale during the high malaria transmission season in Burkina Faso. This paper reports the prevalence of microscopic and submicroscopic malaria infection at the outset and after the first round of SMC in children under 5 years old in Bama, Burkina Faso, as well as host and parasite factors involved in mediating the efficacy and tolerability of SMC.

Methods
Two sequential cross-sectional surveys were conducted in late July and August 2017 during the first month of SMC in a rural area in southwest Burkina Faso. Blood smears and dried blood spots were collected from 106 to 93 children under five, respectively, at the start of SMC and again 3 weeks later. Malaria infection was detected by microscopy and by PCR from dried blood spots. For all children, day 7 plasma concentrations of desethylamodiaquine (DEAQ) were measured and CYP2C8 genetic variants influencing AQ metabolism were genotyped. Samples were additionally genotyped for pfcrt K76T and pfmdr1 N86Y, molecular markers associated with reduced amodiaquine susceptibility.

Results
2.8% (3/106) of children were positive for Plasmodium falciparum infection by microscopy and 13.2% (14/106) by nested PCR within 2 days of SMC administration. Three weeks after SMC administration, in the same households, 4.3% (4/93) of samples were positive by microscopy and 14.0% (13/93) by PCR (p = 0.0007). CYP2C8*2, associated with impaired amodiaquine metabolism, was common with an allelic frequency of 17.1% (95% CI  10.0–24.2). Day 7 concentration of DEAQ ranged from 0.48 to 362.80 ng/mL with a median concentration of 56.34 ng/mL. Pfmdr1 N86 predominated at both time points, whilst a non-significant trend towards a higher prevalence of pfcrt 76T was seen at week 3.

Conclusion
This study showed a moderate prevalence of low-level malaria parasitaemia in children 3 weeks following SMC during the first month of administration. Day 7 concentrations of the active DEAQ metabolite varied widely, likely reflecting variability in adherence and possibly metabolism. These findings highlight factors that may contribute to the effectiveness of SMC in children in a high transmission setting.