bluuebunny/crossref_metadata_2025_split huggingface dataset:
Rickettsia spp. in rodent-attached ticks in Estonia and first evidence of spotted fever group Rickettsia species Candidatus Rickettsia uralica in Europe
Authors: Vikentjeva Maria , Geller Julia , Remm Jaanus , Golovljova Irina 
Published: January 2021

Abstract
Background
Rickettsia spp. are human pathogens that cause a number of diseases and are transmitted by arthropods, such as ixodid ticks. Estonia is one of few regions where the distribution area of two medically important tick species, Ixodes persulcatus and I. ricinus, overlaps. The nidicolous rodent-associated Ixodestrianguliceps has also recently been shown to be present in Estonia. Although no data are available on human disease(s) caused by tick-borne Rickettsia spp. in Estonia, the presence of three Rickettsia species in non-nidicolous ticks has been previously reported. The aim of this study was to detect, identify and partially characterize Rickettsia species in nidicolous and non-nidicolous ticks attached to rodents in Estonia.

Results
Larvae and nymphs of I.ricinus (n = 1004), I. persulcatus (n = 75) and I.trianguliceps (n = 117), all removed from rodents and shrews caught in different parts of Estonia, were studied for the presence of Rickettsia spp. by nested PCR. Ticks were collected from 314 small animals of five species [Myodes glareolus (bank voles), Apodemus flavicollis (yellow necked mice), A.agrarius (striped field mice), Microtus subterranius (pine voles) and Sorex araneus (common shrews)]. Rickettsial DNA was detected in 8.7% (103/1186) of the studied ticks. In addition to identifying R.helvetica, which had been previously found in questing ticks, we report here the first time that the recently described I.trianguliceps-associated Candidatus Rickettsia uralica has been identified west of the Ural Mountains.

Graphical Abstract
Molecular characterization of the waterborne pathogens Cryptosporidium spp., Giardia duodenalis, Enterocytozoon bieneusi, Cyclospora cayetanensis and Eimeria spp. in wastewater and sewage in Guangzhou, China
Authors: Fan Yingying , Wang Xinrui , Yang Ruohong , Zhao Wentao , Li Na , Guo Yaqiong , Xiao Lihua , Feng Yaoyu 
Published: January 2021

Abstract
Background
The waterborne pathogens Cryptosporidium spp., Giardia duodenalis, Enterocytozoon bieneusi and Cyclospora cayetanensis can cause intestinal diseases in humans. An understanding of their occurrence and transport in the environment is essential for accurate quantitative microbial risk assessment.

Methods
A total of 238 influent samples were collected from four wastewater treatment plants (WWTPs) and 88 samples from eight sewer locations in Guangzhou, China. PCR-based tools were used to detect and genetically characterize Cryptosporidium spp., G. duodenalis and E. bieneusi. Eimeria spp. and Cyclospora spp. were also analyzed to assess the sources of Cryptosporidium spp., G. duodenalis and E. bieneusi in wastewater.

Results
The overall occurrence rates in the WWTP and sewer samples were 14.3% (34/238) and 13.6% (12/88) for Cryptosporidium spp., 55.5% (132/238) and 33.0% (29/88) for G. duodenalis, 56.3% (134/238) and 26.1% (23/88) for E. bieneusi and 45.4% (108/238) and 47.7% (42/88) for Eimeria spp., respectively. Altogether, 11 Cryptosporidium species and genotypes, six G. duodenalis genotypes, 11 E. bieneusi genotypes and four C. cayetanensis were found, together with the presence of nine Eimeria species. The common occurrence of Cryptosporidium rat genotype IV, C. muris and Eimeria papillata and E. nieschulzi suggested that rodents were significant sources of the enteric pathogens detected in the wastewater samples.

Conclusions
While the dominant Cryptosporidium spp. detected in the raw wastewater sampled in this study are not pathogenic to humans, the widely detected G. duodenalis assemblage A and E. bieneusi genotypes D and Type IV are well-known zoonotic pathogens. Further studies are needed to monitor the occurrence of these waterborne pathogens in WWTPs to better understand their transmission and environmental transport in China.

Graphical Abstract
DDX1 from Cherry valley duck mediates signaling pathways and anti-NDRV activity
Authors: Zhang Huihui , Song Xingdong , Li Tianxu , Wang Jinchao , Xing Bin , Zhai Xinyu , Luo Jinjian , Hu Xiaofang , Hou Xiaolan , Wei Liangmeng 
Published: January 2021

AbstractNovel duck reovirus (NDRV) causes severe economic losses to the duck industry, which is characterized by hemorrhagic spots and necrotic foci of the livers and spleens. DEAD-box helicase 1 (DDX1) plays a critical role in the innate immune system against viral infection. However, the role of duck DDX1 (duDDX1) in anti-RNA virus infection, especially in the anti-NDRV infection, has yet to be elucidated. In the present study, the full-length cDNA of duDDX1 (2223 bp encode 740 amino acids) was firstly cloned from the spleen of healthy Cherry valley ducks, and the phylogenetic tree indicated that the duDDX1 has the closest relationship with Anas platyrhynchos in the bird branch. The duDDX1 mRNA was widely distributed in all tested tissues, especially in the duodenum, liver, and spleen. Overexpression of duDDX1 in primary duck embryo fibroblast (DEF) cells triggered the activation of transcription factors IRF-7 and NF-κB, as well as IFN-β expression, and the expression of the Toll-like receptors (TLR2, TLR3, and TLR4) was significantly increased. Importantly, after overexpressing or knocking down duDDX1 and infecting NDRV in DEF cells, duDDX1 inhibits the replication of NDRV virus and also regulates the expression of pattern recognition receptors and cytokines. This indicates that duDDX1 may play an important role in the innate immune response of ducks to NDRV. Collectively, we first cloned DDX1 from ducks and analyzed its biological functions. Secondly, we proved that duck DDX1 participates in anti-NDRV infection, and innovated new ideas for the prevention and control of duck virus infection.
Spatiotemporal variability and trends of rainfall and its association with Pacific Ocean Sea surface temperature in West Harerge Zone, Eastern Ethiopia
Authors: Bayable Getachew , Amare Gedamu , Alemu Getnet , Gashaw Temesgen 
Published: January 2021

Abstract
Background
Rainfall variability exceedingly affects agriculture in Ethiopia, particularly in the eastern region where rainfall is relatively scarce. Hence, understanding the spatiotemporal variability of rainfall is indispensable for planning mitigation measures during high and low rainfall seasons. This study examined the spatiotemporal variability and trends of rainfall in the West Harerge Zone, eastern Ethiopia.

Method
The coefficient of variation (CV) and standardized anomaly index (SAI) were used to analyze rainfall variability while Mann-Kendall (MK) trend test and Sen’s slop estimator were employed to examine the trend and magnitude of the rainfall changes, respectively. The association between rainfall and Pacific Ocean Sea Surface Temperature (SST) was also evaluated by Pearson correlation coefficient (r).

Results
The annual rainfall CV during 1983–2019 periods is between 12 and 19.36% while the seasonal rainfall CV extends from 15–28.49%, 24–35.58%, and 38–75.9% for average Kiremt (June–September), Belg (February–May), and Bega (October–January) seasons, respectively (1983–2019). On the monthly basis, the trends of rainfall decreased in all months except in July, October, and November. However, the trends were not statistically significant (α = 0.05), unlike in November. On a seasonal basis, the trends of mean Kiremt and Belg seasons rainfall decreased while it increased in Bega season although it is not statistically significant. Moreover, the annual rainfall showed a non-significant decreasing trend. The findings also revealed that the correlation between rainfall and Pacific Ocean SST was negative for Kiremt while positive for Belg and Bega seasons. Besides, annual rainfall and Pacific Ocean SST was negatively correlated.

Conclusions
High spatial and temporal rainfall variability was observed at the monthly, seasonal, and annual time scales. Seasonal rainfall has high inter-annual variability in the dry season (Bega) than other seasons. The trends in rainfall were decreased in most of the months. Besides, the trend of rainfall decreased in the annual, Belg and Kiremt season while increased in the Bega season. The study also indicated that the occurrence of droughts in the study area was associated with ENSO events like most other parts of Ethiopia and East Africa.
The effect of incorporating an arterial pH target during apnea test for brain death determination
Authors: Migdady Ibrahim , Amin Moein , Shoskes Aaron , Hassett Catherine , Cho Sung-Min , George Pravin , Rae-Grant Alexander 
Published: January 2021

AbstractBackgroundPersistent apnea despite an adequate rise in arterial pressure of CO2is an essential component of the criteria for brain death (BD) determination. Current guidelines vary regarding the utility of arterial pH changes during the apnea test (AT). We aimed to study the effect of incorporating an arterial pH target < 7.30 during the AT (in addition to the existing PaCO2threshold) on brain death declarations.MethodsWe performed retrospective analysis of consecutive adult patients who were diagnosed with BD and underwent AT at the Cleveland Clinic over the last 10 years. Data regarding baseline and post-AT blood gas analyses were collected and analyzed.ResultsNinety-eight patients underwent AT in the study period, which was positive in 89 (91%) and inconclusive in 9 (9%) patients. The mean age was 50 years old (standard deviation [SD] 16) and 54 (55%) were female. The most common etiology BD was hypoxic ischemic brain injury (HIBI) due to cardiac arrest (42%). Compared to those with positive AT, patients with inconclusive AT had a higher post-AT pH (7.24 vs 7.17,p= 0.01), lower PaO2(47 vs 145,p< 0.01), and a lower PaCO2(55 vs 73,p= 0.01). Among patients with a positive AT using PaCO2threshold alone, the frequency of patients with post-AT pH < 7.30 was 95% (83/87).ConclusionImplementing a BD criteria requiring both arterial pH and PaCO2thresholds reduced the total number of positive ATs; these inconclusive cases would have required longer duration of AT to reach both targets, repeated ATs, or ancillary studies to confirm BD. The impact of this on the overall number BD declarations requires further research.
Luteolin and abyssinone II as potential inhibitors of SARS-CoV-2: an in silico molecular modeling approach in battling the COVID-19 outbreak
Authors: Shawan Mohammad Mahfuz Ali Khan , Halder Sajal Kumar , Hasan Md. Ashraful 
Published: January 2021

Abstract
Background
At present, the entire world is in a war against COVID-19 pandemic which has gradually led us toward a more compromised “new normal” life. SARS-CoV-2, the pathogenic microorganism liable for the recent COVID-19 outbreak, is extremely contagious in nature resulting in an unusual number of infections and death globally. The lack of clinically proven therapeutic intervention for COVID-19 has dragged the world’s healthcare system into the biggest challenge. Therefore, development of an efficient treatment scheme is now in great demand. Screening of different biologically active plant-based natural compounds could be a useful strategy for combating this pandemic. In the present research, a collection of 43 flavonoids of 7 different classes with previously recorded antiviral activity was evaluated via computational and bioinformatics tools for their impeding capacity against SARS-CoV-2. In silico drug likeness, pharmacophore and Absorption, Distribution, Metabolism, Excretion and Toxicity (ADMET) profile analysis of the finest ligands were carried out using DataWarrior, DruLiTo and admetSAR programs, respectively. Molecular docking was executed by AutoDock Vina, while molecular dynamics simulation of the target protein–ligand bound complexes was done using nanoscalable molecular dynamics and visual molecular dynamics software package. Finally, the molecular target analysis of the selected ligands within Homo sapiens was conducted with SwissTargetPredcition web server.

Results
Out of the forty-three flavonoids, luteolin and abyssinone II were found to develop successful docked complex within the binding sites of target proteins in terms of lowest binding free energy and inhibition constant. The root mean square deviation and root mean square fluctuation values of the docked complex displayed stable interaction and efficient binding between the ligands and target proteins. Both of the flavonoids were found to be safe for human use and possessed good drug likeness properties and target accuracy.

Conclusions
Conclusively, the current study proposes that luteolin and abyssinone II might act as potential therapeutic candidates for SARS-CoV-2 infection. In vivo and in vitro experiments, however, should be taken under consideration to determine the efficiency and to demonstrate the mechanism of action.
Immunological perspectives on the pathogenesis, diagnosis, prevention and treatment of COVID-19
Authors: Ni Yanghong , Alu Aqu , Lei Hong , Wang Yang , Wu Min , Wei Xiawei 
Published: January 2021

AbstractCoronavirus disease 2019 (COVID-19) is an acute respiratory disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-COV-2). COVID-19 can spread to the entire body and cause multiple organ failure. It is a daunting challenge to control the fast growing worldwide pandemic because effective prevention and treatment strategies are unavailable currently. Generally, the immune response of the human body triggered by viral infection is essential for the elimination of the virus. However, severe COVID-19 patients may manifest dysregulated immune responses, such as lymphopenia, lymphocyte exhaustion, exacerbated antibody response, cytokine release syndrome (CRS), etc. Understanding of these immunological characteristics may help identify better approaches for diagnosis, prognosis and treatment of COVID-19 patients. As specific anti-viral agents are notoriously difficult to develop, strategies for modulating the immune responses by either developing novel vaccines or using immunotherapy hold great promise to improve the management of SARS-CoV-2 infection.
Sperm-borne miR-202 targets SEPT7 and regulates first cleavage of bovine embryos via cytoskeletal remodeling
Authors: Wang Mengyun , Du Yue , Gao Song , Wang Zheng , Qu Pengxiang , Gao Yang , Wang Jingyi , Liu Zhengqi , Zhang Jingcheng , Zhang Yong , Qing Suzhu , Wang Yongsheng 
Published: January 2021

ABSTRACT
In mammals, sperm-borne regulators can be transferred to oocytes during fertilization and have different effects on the formation of pronuclei, the first cleavage of zygotes, the development of preimplantation embryos and even the metabolism of individuals after birth. The regulatory role of sperm microRNAs (miRNAs) in the development of bovine preimplantation embryos has not been reported in detail. By constructing and screening miRNA expression libraries, we found that miR-202 was highly enriched in bovine sperm. As a target gene of miR-202, co-injection of SEPT7 siRNA can partially reverse the accelerated first cleavage of bovine embryos caused by miR-202 inhibitor. In addition, both a miR-202 mimic and SEPT7 siRNA delayed the first cleavage of somatic cell nuclear transfer (SCNT) embryos, suggesting that miR-202-SEPT7 mediates the delay of first cleavage of bovine embryos. By further exploring the relationship between miR-202/SEPT7, HDAC6 and acetylated α-tubulin during embryonic development, we investigated how sperm-borne miR-202 regulates the first cleavage process of bovine embryos by SEPT7 and demonstrate the potential of sperm-borne miRNAs to improve the efficiency of SCNT.
Is Oxygen Diffusion Faster in Bulk CeO2 or on a (111)-CeO2 Surface? A Theoretical Study
Authors: Sakti Aditya Wibawa , Chou Chien-Pin , Nishimura Yoshifumi , Nakai Hiromi 
Published: January 2021

Abstract
Ceria (CeO2) is a promising metal-oxide support that is used in three-way catalysis (TWC). The activity of ceria-supported TWC depends on the location and concentration of oxygen vacancies. Oxygen diffusion can occur once the oxygen vacancy is created, and it leads to enhanced catalytic activity. In this study, the density-functional tight-binding method was used to estimate the free-energy barriers of oxygen diffusion in bulk CeO2 and on a (111)-CeO2 surface. The reconstructed free-energy surfaces from metadynamics sampling show that the diffusion in the bulk CeO2 is faster than that on the (111)-CeO2 surface, with activation barriers of 7.4 and 31.6 kcal/mol, respectively.
Multimorbidity patterns and their relationship to mortality in the US older adult population
Authors: Zheng D. Diane , Loewenstein David A. , Christ Sharon L. , Feaster Daniel J. , Lam Byron L. , McCollister Kathryn E. , Curiel-Cid Rosie E. , Lee David J. 
Published: January 2021

Background
Understanding patterns of multimorbidity in the US older adult population and their relationship with mortality is important for reducing healthcare utilization and improving health. Previous investigations measured multimorbidity as counts of conditions rather than specific combination of conditions.

Methods
This cross-sectional study with longitudinal mortality follow-up employed latent class analysis (LCA) to develop clinically meaningful subgroups of participants aged 50 and older with different combinations of 13 chronic conditions from the National Health Interview Survey 2002–2014. Mortality linkage with National Death Index was performed through December 2015 for 166,126 participants. Survival analyses were conducted to assess the relationships between LCA classes and all-cause mortality and cause specific mortalities.

Results
LCA identified five multimorbidity groups with primary characteristics: “healthy” (51.5%), “age-associated chronic conditions” (33.6%), “respiratory conditions” (7.3%), “cognitively impaired” (4.3%) and “complex cardiometabolic” (3.2%). Covariate-adjusted survival analysis indicated “complex cardiometabolic” class had the highest mortality with a Hazard Ratio (HR) of 5.30, 99.5% CI [4.52, 6.22]; followed by “cognitively impaired” class (3.34 [2.93, 3.81]); “respiratory condition” class (2.14 [1.87, 2.46]); and “age-associated chronic conditions” class (1.81 [1.66, 1.98]). Patterns of multimorbidity classes were strongly associated with the primary underlying cause of death. The “cognitively impaired” class reported similar number of conditions compared to the “respiratory condition” class but had significantly higher mortality (3.8 vs 3.7 conditions, HR = 1.56 [1.32, 1.85]).

Conclusion
We demonstrated that LCA method is effective in classifying clinically meaningful multimorbidity subgroup. Specific combinations of conditions including cognitive impairment and depressive symptoms have a substantial detrimental impact on the mortality of older adults. The numbers of chronic conditions experienced by older adults is not always proportional to mortality risk. Our findings provide valuable information for identifying high risk older adults with multimorbidity to facilitate early intervention to treat chronic conditions and reduce mortality.
IL-10 and class 1 histone deacetylases act synergistically and independently on the secretion of proinflammatory mediators in alveolar macrophages
Authors: Stanfield Brent A. , Purves Todd , Palmer Scott , Sullenger Bruce , Welty-Wolf Karen , Haines Krista , Agarwal Suresh , Kasotakis George 
Published: January 2021

IntroductionAnti-inflammatory cytokine IL-10 suppresses pro-inflammatory IL-12b expression after Lipopolysaccharide (LPS) stimulation in colonic macrophages, as part of the innate immunity Toll-Like Receptor (TLR)-NF-κB activation system. This homeostatic mechanism limits excess inflammation in the intestinal mucosa, as it constantly interacts with the gut flora. This effect is reversed with Histone Deacetylase 3 (HDAC3), a class I HDAC, siRNA, suggesting it is mediated through HDAC3. Given alveolar macrophages’ prominent role in Acute Lung Injury (ALI), we aim to determine whether a similar regulatory mechanism exists in the typically sterile pulmonary microenvironment.MethodsLevels of mRNA and protein for IL-10, and IL-12b were determined by qPCR and ELISA/Western Blot respectively in naïve and LPS-stimulated alveolar macrophages. Expression of the NF-κB intermediaries was also similarly assessed. Experiments were repeated with AS101 (an IL-10 protein synthesis inhibitor), MS-275 (a selective class 1 HDAC inhibitor), or both.ResultsLPS stimulation upregulated all proinflammatory mediators assayed in this study. In the presence of LPS, inhibition of IL-10 and/or class 1 HDACs resulted in both synergistic and independent effects on these signaling molecules. Quantitative reverse-transcriptase PCR on key components of the TLR4 signaling cascade demonstrated significant diversity in IL-10 and related gene expression in the presence of LPS. Inhibition of IL-10 secretion and/or class 1 HDACs in the presence of LPS independently affected the transcription of MyD88, IRAK1, Rela and the NF-κB p50 subunit. Interestingly, by quantitative ELISA inhibition of IL-10 secretion and/or class 1 HDACs in the presence of LPS independently affected the secretion of not only IL-10, IL-12b, and TNFα, but also proinflammatory mediators CXCL2, IL-6, and MIF. These results suggest that IL-10 and class 1 HDAC activity regulate both independent and synergistic mechanisms of proinflammatory cytokine/chemokine signaling.ConclusionsAlveolar macrophages after inflammatory stimulation upregulate both IL-10 and IL-12b production, in a highly class 1 HDAC-dependent manner. Class 1 HDACs appear to help maintain the balance between the pro- and anti-inflammatory IL-12b and IL-10 respectively. Class 1 HDACs may be considered as targets for the macrophage-initiated pulmonary inflammation in ALI in a preclinical setting.
Clinical characteristics of treatment-resistant depression in adults in Hungary: Real-world evidence from a 7-year-long retrospective data analysis
Authors: Döme Péter , Kunovszki Péter , Takács Péter , Fehér László , Balázs Tamás , Dede Károly , Mulhern-Haughey Siobhán , Barbreau Sébastien , Rihmer Zoltán 
Published: January 2021

Purpose
Treatment-resistant depression (TRD) is associated with a poor quality of life and high economic burden. This observational retrospective epidemiological study aimed to estimate the proportion of patients with TRD within a cohort of patients with major depressive disorder (MDD) in Hungary and examine the mortality and comorbidities of patients with and without TRD.

Patients and methods
This study included patients with MDD who experienced onset of a new depressive episode between 01 January 2009 and 31 August 2015, using data from a nationwide, longitudinal database.

Results
Overall, 99,531 patients were included in the MDD cohort, of which 8,268 (8.3%) also met the criteria for TRD. The overall survival of non-TRD patients was longer than in TRD patients; the risk of mortality for TRD patients was significantly higher than of non-TRD patients (HR [CI] 1.381 [1.212–1.571]; p<0.001). Patients with TRD had a significantly higher probability of having “Neurotic, stress-related and somatoform disordersˮ, autoimmune conditions, cardio- or cerebrovascular diseases, thyroid gland diseases and self-harming behaviour not resulting in death than non-TRD patients (for all comparisons, p values were less than 0.005).

Discussion
To our best knowledge, this is the first study to assess the frequency of TRD in Hungary. In a cohort of Hungarian MDD patients, we have found that the proportion of TRD (~8.3%) is comparable to those reported in previous studies with similar methodology from other countries. The majority of our other main findings (e.g. more frequent self-harming behaviour, increased risk of “Neurotic, stress-related and somatoform disordersˮ and higher overall mortality in TRD subjects) are also in line with previous results from other countries. Taking the substantial proportion of patients with TRD into consideration, a more comprehensive and targeted treatment strategy would be required for these individuals.