bluuebunny/crossref_metadata_2025_split huggingface dataset:
The long and winding road to happiness: A randomized controlled trial and cost-effectiveness analysis of a positive psychology intervention for lonely people with health problems and a low socio-economic status
Authors: Weiss Laura A. , Oude Voshaar Martijn A. H. , Bohlmeijer Ernst T. , Westerhof Gerben J. 
Published: June 2020

AbstractBackgroundOur objective was to evaluate the effectiveness and cost-effectiveness of the positive psychology intervention ‘Happiness Route’ compared to an active control condition in a vulnerable population with an accumulation of health and psychosocial problems.MethodsWe conducted a randomized, single-blind, actively-controlled, parallel group study in seven municipalities in the Netherlands. To be eligible, participants had to experience loneliness, health problems and low socio-economic status. Each group received several home visits by a counsellor (two in the control condition, two to six in the experimental condition). In the Happiness Route, a happiness-based approach was used, whereas the control condition used a traditional problem-based approach. The primary outcome was well-being, measured with the Mental Health Continuum-Short Form (MHC-SF).ResultsFifty-eight participants were randomized to the Happiness Route, 50 to the control condition. Participants were severely lonely, had on average three health problems and less than 5% had paid work. The total MHC-SF score, emotional and social well-being, depression and loneliness improved significantly over the nine-month period in both conditions (p < .05), but there were no significant changes between the conditions across time. Languishing decreased significantly from 33% at baseline to 16% at follow-up among the Happiness Route participants but did not change significantly in the control condition. No significant improvement over time was found in psychological well-being, resilience, purpose in life, health-related quality of life and social participation. Cost-effectiveness analysis showed that expected saved costs per QALY lost was €219,948 for the Happiness Route, relative to the control condition. The probability was 83% that the Happiness Route was cost saving and 54% that the Happiness Route was cost-effective at a willingness to accept a threshold of €100,000.ConclusionsMental health status of both groups improved considerably. However, we could not demonstrate that the Happiness Route yielded better health outcomes compared to the control condition. Nevertheless, the results of the cost-effectiveness analysis suggested that the Happiness Route is an acceptable intervention from a health-economic point of view. Our results should be viewed in light of the fact that we could not include the planned number of participants.Trial registrationNetherlands Trial Register:NTR3377. Registered 2 Apr 2012.
CLN5 in heterozygosis may protect against the development of tumors in a VHL patient
Authors: de Rojas-P Isabel , Albiñana Virginia , Recio-Poveda Lucía , Rodriguez-Rufián Amanda , Cuesta Ángel M. , Botella Luisa-María 
Published: June 2020

AbstractVon Hippel-Lindau syndrome (VHL) is a rare disease of dominant inheritance that increases susceptibility to tumor development, with a complete penetrance at the age of 60. In this report, we present the unprecedented case of a VHL carrier who remains healthy at 72. Under the course of this study, it was discovered that this patient carries a mutation for a second rare disease, Neuronal Ceroid Lipofuscinosis (NCL or CNL). We hypothesize that the CLN mutation she carries offers a protective effect, preventing tumor development in the cells potentially suffering a VHL second hit mutation. To test this hypothesis, we ran a series of molecular experiments and confirmed that cell viability of primary endothelial cells decreases upon CLN5 silencing. Our results further elucidate the cell biology implications of two rare diseases interacting.
Oct4 promotes M2 macrophage polarization through upregulation of macrophage colony-stimulating factor in lung cancer
Authors: Lu Chia-Sing , Shiau Ai-Li , Su Bing-Hua , Hsu Tsui-Shan , Wang Chung-Teng , Su Yu-Chu , Tsai Ming-Shian , Feng Yin-Hsun , Tseng Yau-Lin , Yen Yi-Ting , Wu Chao-Liang , Shieh Gia-Shing 
Published: June 2020

Abstract
Background
Expression of Oct4 maintains cancer stem cell (CSC)-like properties in lung cancer cells and is correlated with poor prognosis of lung adenocarcinoma. M2-type tumor-associated macrophages (TAMs) promote cancer cell migration and metastasis. Tumor microenvironments promote monocyte differentiation into M2 TAMs via a complex cytokine-based connection. We explored the role of Oct4 in cytokine secretion in lung cancer and its impact on M2 TAM polarization.

Methods
Monocytes co-cultured with the conditioned medium from Oct4-overexpressing lung cancer cells were used to investigate M2 TAM differentiation. The inflammatory factors in the conditioned medium of Oct4-overexpressing A549 cells were examined using human inflammation antibody arrays. The correlations of Oct4, macrophage colony-stimulating factor (M-CSF), and M2 TAMs were validated in lung cancer cells, syngeneic mouse lung tumor models, and clinical samples of non-small cell lung cancer (NSCLC).

Results
Oct4-overexpressing A549 cells expressed elevated levels of M-CSF, which contributed to increased M2 macrophages and enhanced tumor migration. Overexpression of Oct4 enhanced tumor growth and reduced the survival of lung tumor-bearing mice, which was correlated with increased number of M2 macrophages in lung cancer. Notably, NSCLC patients with high expression levels of Oct4, M-CSF, and M2 TAMs had the poorest recurrence-free survival. A positive correlation between Oct4, M-CSF, and M2 TAMs was observed in the tumor tissue of NSCLC patient. Treatment with all-trans retinoic acid exerted anti-tumor effects and reduced M2 TAMs in tumor-bearing mice.

Conclusions
Our results indicate that Oct4 expressed by lung cancer cells promotes M2 macrophage polarization through upregulation of M-CSF secretion, leading to cancer growth and metastasis. Our findings also implicate that the Oct4/M-CSF axis in M2 macrophage polarization may be potential therapeutic targets for lung cancer.
Proteomic signatures of metronidazole-resistant Trichomonas vaginalis reveal novel proteins associated with drug resistance
Authors: Lin Hsin-Chung , Chu Lichieh Julie , Huang Po-Jung , Cheng Wei-Hung , Zheng Yu-Hsing , Huang Ching-Yun , Hong Shu-Wen , Chen Lih-Chyang , Lin Hsin-An , Wang Jui-Yang , Chen Ruei-Min , Lin Wei-Ning , Tang Petrus , Huang Kuo-Yang 
Published: June 2020

Abstract
Background
Trichomoniasis is the most common non-viral sexually transmitted disease caused by the protozoan parasite Trichomonas vaginalis. Metronidazole (MTZ) is a widely used drug for the treatment of trichomoniasis; however, increased resistance of the parasite to MTZ has emerged as a highly problematic public health issue.

Methods
We conducted iTRAQ-based analysis to profile the proteomes of MTZ-sensitive (MTZ-S) and MTZ-resistant (MTZ-R) parasites. STRING and gene set enrichment analysis (GESA) were utilized to explore the protein-protein interaction networks and enriched pathways of the differentially expressed proteins, respectively. Proteins potentially related to MTZ resistance were selected for functional validation.

Results
A total of 3123 proteins were identified from the MTZ-S and MTZ-R proteomes in response to drug treatment. Among the identified proteins, 304 proteins were differentially expressed in the MTZ-R proteome, including 228 upregulated and 76 downregulated proteins. GSEA showed that the amino acid-related metabolism, including arginine, proline, alanine, aspartate, and glutamate are the most upregulated pathways in the MTZ-R proteome, whereas oxidative phosphorylation is the most downregulated pathway. Ten proteins categorized into the gene set of oxidative phosphorylation were ATP synthase subunit-related proteins. Drug resistance was further examined in MTZ-S parasites pretreated with the ATP synthase inhibitors oligomycin and bafilomycin A1, showing enhanced MTZ resistance and potential roles of ATP synthase in drug susceptibility.

Conclusions
We provide novel insights into previously unidentified proteins associated with MTZ resistance, paving the way for future development of new drugs against MTZ-refractory trichomoniasis.
DAMEfinder: a method to detect differential allele-specific methylation
Authors: Orjuela Stephany , Machlab Dania , Menigatti Mirco , Marra Giancarlo , Robinson Mark D. 
Published: June 2020

AbstractBackgroundDNA methylation is a highly studied epigenetic signature that is associated with regulation of gene expression, whereby genes with high levels of promoter methylation are generally repressed. Genomic imprinting occurs when one of the parental alleles is methylated, i.e., when there is inherited allele-specific methylation (ASM). A special case of imprinting occurs during X chromosome inactivation in females, where one of the two X chromosomes is silenced, to achieve dosage compensation between the sexes. Another more widespread form of ASM is sequence dependent (SD-ASM), where ASM is linked to a nearby heterozygous single nucleotide polymorphism (SNP).ResultsWe developed a method to screen for genomic regions that exhibit loss or gain of ASM in samples from two conditions (treatments, diseases, etc.). The method relies on the availability of bisulfite sequencing data from multiple samples of the two conditions. We leverage other established computational methods to screen for these regions within a new R package called DAMEfinder. It calculates an ASM score for all CpG sites or pairs in the genome of each sample, and then quantifies the change in ASM between conditions. It then clusters nearby CpG sites with consistent change into regions. In the absence of SNP information, our method relies only on reads to quantify ASM. This novel ASM score compares favorably to current methods that also screen for ASM. Not only does it easily discern between imprinted and non-imprinted regions, but also females from males based on X chromosome inactivation. We also applied DAMEfinder to a colorectal cancer dataset and observed that colorectal cancer subtypes are distinguishable according to their ASM signature. We also re-discover known cases of loss of imprinting.ConclusionWe have designed DAMEfinder to detect regions of differential ASM (DAMEs), which is a more refined definition of differential methylation, and can therefore help in breaking down the complexity of DNA methylation and its influence in development and disease.
Parasitic infections in irritable bowel syndrome patients: evidence to propose a possible link, based on a case–control study in the south of Iran
Authors: Shafiei Zohreh , Esfandiari Farideh , Sarkari Bahador , Rezaei Zahra , Fatahi Mohammad Reza , Hosseini Asl Seyed Mohammad Kazem 
Published: June 2020

Abstract
Objectives
The current study aimed to evaluate the prevalence of parasitic infections and their possible association with irritable bowel syndrome (IBS), through a case–control study. Stool samples were collected from patients with IBS and healthy subjects and were examined microscopically to detect intestinal parasites.

Results
A total of 200 subjects were enrolled in the study including 100 patients with IBS and 100 healthy controls. The patients were selected based on the Rome III criteria. Of the 100 patients with IBS, 65 (65%) were female and 35 (35%) were male, with a mean age of 42.57 (± 4.07) years. Of these, 30 (30%) were infected with at least one intestinal parasite; the most common ones were Blastocystis hominis and Giardia lamblia. Of the control cases, 64 (64%) were female and 36 (36%) were male, with a mean age of 41.82 (± 11.75) years. Of these, 16 (16%) were infected with at least one intestinal parasite; the most common were B. hominis and Endolimax. There was a significant difference between the rate of parasitic infections between the patients with IBS and the control in particular, B. hominis and G. lamblia. The findings of the study support a possible link between parasitic infections and IBS.
Differential cellular proliferation underlies heterochronic generation of cranial diversity in phyllostomid bats
Authors: Camacho Jasmin , Moon Rachel , Smith Samantha K. , Lin Jacky D. , Randolph Charles , Rasweiler John J. , Behringer Richard R. , Abzhanov Arhat 
Published: June 2020

AbstractBackgroundSkull diversity in the neotropical leaf-nosed bats (Phyllostomidae) evolved through a heterochronic process called peramorphosis, with underlying causes varying by subfamily. The nectar-eating (subfamily Glossophaginae) and blood-eating (subfamily Desmondontinae) groups originate from insect-eating ancestors and generate their uniquely shaped faces and skulls by extending the ancestral ontogenetic program, appending new developmental stages and demonstrating peramorphosis by hypermorphosis. However, the fruit-eating phyllostomids (subfamilies Carollinae and Stenodermatinae) adjust their craniofacial development by speeding up certain developmental processes, displaying peramorphosis by acceleration. We hypothesized that these two forms of peramorphosis detected by our morphometric studies could be explained by differential growth and investigated cell proliferation during craniofacial morphogenesis.ResultsWe obtained cranial tissues from four wild-caught bat species representing a range of facial diversity and labeled mitotic cells using immunohistochemistry. During craniofacial development, all bats display a conserved spatiotemporal distribution of proliferative cells with distinguishable zones of elevated mitosis. These areas were identified as modules by the spatial distribution analysis. Ancestral state reconstruction of proliferation rates and patterns in the facial module between species provided support, and a degree of explanation, for the developmental mechanisms underlying the two models of peramorphosis. In the long-faced species,Glossophaga soricina, whose facial shape evolved by hypermorphosis, cell proliferation rate is maintained at lower levels and for a longer period of time compared to the outgroup speciesMiniopterus natalensis. In both species of studied short-faced fruit bats,Carollia perspicillataandArtibeus jamaicensis, which evolved under the acceleration model, cell proliferation rate is increased compared to the outgroup.ConclusionsThis is the first study which links differential cellular proliferation and developmental modularity with heterochronic developmental changes, leading to the evolution of adaptive cranial diversity in an important group of mammals.
Maslinic acid induces anticancer effects in human neuroblastoma cells mediated via apoptosis induction and caspase activation, inhibition of cell migration and invasion and targeting MAPK/ERK signaling pathway
Authors: Liu Yusheng , Lu Hongting , Dong Qian , Hao Xiwei , Qiao Lingyan 
Published: June 2020

AbstractMaslinic acid is an active member of pentacyclic triterpenes predominantly found in dietary plants including hawthorn berries and olive fruit skins. It has been reported to show immense pharmacological and biological importance including anticancer property. This research was initiated to explore the anticancer potential of maslinic acid against human neuroblastoma. The effects of maslinic acid on cellular apoptosis, ROS generation, cell migration and invasion, caspase activation and targeting MAPK/ERK signaling pathway were investigated. The proliferation percentage was calculated by performing of MTT assay. AO/EB and annexin V/PI staining assays along with western blotting were used to monitor the apoptosis and expressions of apoptosis connected proteins. Spectrofluorometry was used for ROS monitoring. To assess the anti-metastatic effects of maslinic acid on neuroblastoma cells, transwell chambers assays for migration as well as invasion were executed. Western blotting was implemented to establish the expressions of MAPK/ERK signaling pathway connected proteins. Results evidenced remarkable anticancer potential of maslinic acid against human neuroblastoma. It induced dose as well as time reliant anti-proliferative effects against SHSY-5Y cells selectively. The underlying mechanism of cancer suppressive effects of maslinic acid was found to mediate via caspase-dependent apoptosis. Further, ROS production amplified terrifically with exposure of SHSY-5Y to higher maslinic acid doses. Cell migration and invasion in SHSY-5Y cells were both reduced remarkably by maslinic acid. Finally, the activity of proteins associated with MAPK/ERK signaling pathway was found to be significantly reduced with increasing maslinic acid doses. In conclusion, it was observed that maslinic acid possesses a great anti-neuroblastoma potential and could be considered for its chemotherapy provided further investigations are recommended.
Dynamics of Clostridium genus and hard-cheese spoiling Clostridium species in anaerobic digesters treating agricultural biomass
Authors: Fontana Alessandra , Soldano Mariangela , Bellassi Paolo , Fabbri Claudio , Gallucci Francesco , Morelli Lorenzo , Cappa Fabrizio 
Published: June 2020

AbstractBiogas plants are a widespread renewable energy technology. However, the use of digestate for agronomic purposes has often been a matter of concern. It is controversial whether biogas plants might harbor some pathogenic clostridial species, which represent a biological risk. Moreover, the inhabitance of Clostridium hard-cheese spoiling species in anaerobic digesters can be problematic for hard-cheese manufacturing industries, due to the issue of cheese blowing defects. This study investigated the effect of mesophilic anaerobic digestion processes on the Clostridium consortia distribution over time. Specifically, three lab-scale CSTRs treating agricultural biomass were characterized by considering both the whole microbial community and the cultivable clostridial spores. It is assessed an overall reduction of the Clostridium genus during the anaerobic digestion process. Moreover, it was evidenced a slight, but steady decrease of the cultivable clostridial spores, mainly represented by two pathogenic species, C. perfringens and C. bifermentans, and one hard-cheese spoiling species, C. butyricum. Thus, it is revealed an overall reduction of the clostridial population abundance after the mesophilic anaerobic digestion treatment of agricultural biomass.
Opial integral inequalities for generalized fractional operators with nonsingular kernel
Authors: Mohammed Pshtiwan Othman , Abdeljawad Thabet 
Published: June 2020

AbstractWe consider the well-known classes of functions$\mathcal{U}_{1}(\mathbf{v},\mathtt{k})$U1(v,k)and$\mathcal{U}_{2}(\mathbf{v},\mathtt{k})$U2(v,k), and those of Opial inequalities defined on these classes. In view of these indices, we establish new aspects of the Opial integral inequality and related inequalities, in the context of fractional integrals and derivatives defined using nonsingular kernels, particularly the Caputo–Fabrizio (CF) and Atangana–Baleanu (AB) models of fractional calculus.
Using soil bacterial communities to predict physico-chemical variables and soil quality
Authors: Hermans Syrie M. , Buckley Hannah L. , Case Bradley S. , Curran-Cournane Fiona , Taylor Matthew , Lear Gavin 
Published: June 2020

Abstract
Background
Soil ecosystems consist of complex interactions between biological communities and physico-chemical variables, all of which contribute to the overall quality of soils. Despite this, changes in bacterial communities are ignored by most soil monitoring programs, which are crucial to ensure the sustainability of land management practices. We applied 16S rRNA gene sequencing to determine the bacterial community composition of over 3000 soil samples from 606 sites in New Zealand. Sites were classified as indigenous forests, exotic forest plantations, horticulture, or pastoral grasslands; soil physico-chemical variables related to soil quality were also collected. The composition of soil bacterial communities was then used to predict the land use and soil physico-chemical variables of each site.

Results
Soil bacterial community composition was strongly linked to land use, to the extent where it could correctly determine the type of land use with 85% accuracy. Despite the inherent variation introduced by sampling across ~ 1300 km distance gradient, the bacterial communities could also be used to differentiate sites grouped by key physico-chemical properties with up to 83% accuracy. Further, individual soil variables such as soil pH, nutrient concentrations and bulk density could be predicted; the correlations between predicted and true values ranged from weak (R2 value = 0.35) to strong (R2 value = 0.79). These predictions were accurate enough to allow bacterial communities to assign the correct soil quality scores with 50–95% accuracy.

Conclusions
The inclusion of biological information when monitoring soil quality is crucial if we wish to gain a better, more accurate understanding of how land management impacts the soil ecosystem. We have shown that soil bacterial communities can provide biologically relevant insights on the impacts of land use on soil ecosystems. Furthermore, their ability to indicate changes in individual soil parameters shows that analysing bacterial DNA data can be used to screen soil quality.
Human rabies in China: evidence-based suggestions for improved case detection and data gathering
Authors: Li Hao , Liu Jia-Jia , Ding Shu-Jun , Cai Liang , Feng Yun , Yu Peng-Cheng , Liu Shu-Qing , Lu Xue-Xin , Tao Xiao-Yan , Zhu Wu-Yang 
Published: June 2020

Abstract
Background
China still suffers heavily from rabies, although reported human cases continue to decrease year over year. There are far fewer laboratory-confirmed human cases than clinically diagnosed cases, which is a big problem that needs to be addressed. In this report, we summarize analyses of all specimens from human cases tested in our laboratory over the past 15 years, in order to promote laboratory diagnosis of rabies.

Methods
From 2005 to 2019, a total of 271 samples from 164 suspected rabies cases were collected from local hospitals by the local Centers for Disease Control and Prevention (CDCs) in China. Saliva, cerebrospinal fluid (CSF), serum (blood) and urine were collected for ante-mortem diagnosis, and brain tissue, neck skin tissue and cornea were collected for post-mortem diagnosis. All of the specimens were tested by reverse transcription-polymerase chain reaction (RT-PCR), and brain tissues were also tested using fluorescent antibody test (FAT). The number of positive test results obtained using different fluids or tissues, and at different stages of the disease, were compared using a chi-square test and a more effective sampling program is recommended.

Results
As the national reference laboratory for rabies surveillance in China, our laboratory has tested 271 samples from 164 suspected rabies cases collected by local CDCs since 2005. We found that saliva gave the highest number of positive test results (32%), compared with CSF and other fluids. We also found that serum or blood specimens collected in the last 3 days of life can test positive by RT-PCR.

Conclusions
Serum or blood samples collected in the last 3 days of a patient’s life can be used to measure viral RNA, which means that serum samples, as well as saliva and CSF, can be used to detect viral RNA for anti-mortem diagnosis of rabies. Because of our findings, we have modified our “National Surveillance Project for Human Rabies”, by adding the collection and testing of serum samples from the end of the survival period. This will improve our national surveillance and laboratory diagnosis of human rabies.