bluuebunny/crossref_metadata_2025_split huggingface dataset:
Impact on prostate cancer clinical presentation after non-screening policies at a tertiary-care medical center- a retrospective study
Authors: Ajami Tarek , Durruty Jaime , Mercader Claudia , Rodriguez Leonardo , Ribal Maria J. , Alcaraz Antonio , Vilaseca Antoni 
Published: February 2021

Abstract
Background
In May 2012 the US Preventive Task Force issued a ‘D’ recommendation against routine PSA-based early detection of prostate cancer. This recommendation was implemented progressively in our health system. The aim of this study is to define its impact on prostate cancer staging at a tertiary care institution.

Methods
A retrospective analysis was performed from 2012 until 2015 at a single center. We analyzed the total number of biopsies performed per year and the positive biopsy rate. For those patients with positive biopsies we recorded diagnostic PSA, clinical stage, ISUP grade group, nodal involvement and metastatic status at diagnosis.

Results
A total of 1686 biopsies were analyzed. The positive biopsy rate increased from 25% in 2012 to 40% in 2015 (p < 0.05). No change in median PSA was noticed (p = 0.627). The biopsies detected higher ISUP grades (p = 0.000). In addition, newly diagnosed prostate cancer presented a higher clinical stage (p = 0.005), higher metastatic rates (p = 0.03) and a tendency to higher lymph node involvement although not statistically significant (p = 0.09).

Conclusion
After the 2012 recommendation, patients presented a higher probability of a prostate cancer diagnosis, with a more adverse ISUP group, clinical stage and metastatic disease.
These results should be taken into consideration to implement a risk adapted strategy for prostate cancer screening.
The impact of coronavirus lockdown on oral healthcare and its associated issues of pre-schoolers in China: an online cross-sectional survey
Authors: Liu Chang , Zhang Shuang , Zhang Chenzheng , Tai Baojun , Jiang Han , Du Minquan 
Published: February 2021

Abstract
Background
The sudden outbreak of coronavirus disease (COVID-19) epidemic influenced people’s daily life. During lockdown of Wuhan city, the oral health and its associated issues of preschool children were investigated and guidance for dental clinics when the epidemic were controlled in the future were also provided.

Methods
A national online survey was conducted among preschool children and completed by their caregivers. The questionnaire related to children’s oral health status and care behaviour, caregivers' attitudes. The information was statistically analyzed between Wuhan residents and others residents.

Results
4495 valid questionnaires were collected. In oral health status, during Wuhan lockdown, 60.8%, 35.5% and 18.3% children had self-reported dental caries, toothache and halitosis respectively. In oral health attitudes, respondents who would increase attention to oral health was more than that would decrease. In oral hygiene behaviour, compared to non-Wuhan children, the children in Wuhan became more active in brushing their teeth. In utilization of dental services in the future, less Wuhan residents would choose to have dental visit directly, 28.5% Wuhan residents and 34.7% non-Wuhan residents agreed all of procedures could be done if proper protected.

Conclusions
Oral health status and associated issues of preschool children in Wuhan were significantly different from that of others during lockdown of Wuhan city and in the future. Effective measures should be taken as early as possible to protect children's oral health.
Impact of free newborn care service package on out of pocket expenditure‐evidence from a multicentric study in Nepal
Authors: Sunny Avinash K , Basnet Omkar , Acharya Ankit , Poudel Prajwal , Malqvist Mats , KC Ashish 
Published: February 2021

Abstract
Background
Sustainable Development Goal (SDG) aspires to improve universal health coverage through reduction of Out of Pocket Expenditure (OOPE) and improving the quality of care. In the last two decades, there have been several efforts to reduce the OOPE for maternal and newborn care. In this paper, we evaluate the change in the OOPE for treatment of sick newborn at hospital before and after implementation of a free newborn care (FNC) program in hospitals of Nepal.

Methods
Ministry of Health and Population implemented a free newborn care program which reimbursed the cost of treatment for all sick newborns admitted in public hospitals in Nepal from November 2017. We conducted this pre-post quasi-experimental study with four months of pre-implementation and 12 months of post-implementation of the program in 12 hospitals of Nepal. Logistic regression analysis was conducted for categorical variables and Mann-Whitney test was applied for continuous variables to determine statistically significant differences between pre- and post- intervention period.

Results
A total of 353 sick newborns were admitted into these hospitals before implementation of the FNC program while 1122 sick newborns were admitted after the implementation. Before implementation, 17 % of mothers paid for sick newborn care while after implementation 15.3 % mothers (p-value = 0.59) paid for care. The OOPE for treatment of sick newborn at hospital before implementation was Mean ± SD: US dollar 14.3 + 12.1 and after implementation was Mean ± SD: USD 13.0 ± 9.6 (p-value = 0.71). There were no significant differences in neonatal morbidity after the implementation of the FNC program. The stay in a hospital bed (in days) decreased after the implementation of FNC program (p-value < 0.001) while the cost for medicine increased (p-value = 0.02). The duration of hospital stay (in days) of sick newborns significantly decreased for Hypoxic Ischemic Encephalopathy (HIE) (p-value = 0.04) and neonatal sepsis (p-value < 0.001) after the FNC program was implemented.

Conclusions
We found no change in the OOPE for sick newborn care following implementation of the FNC Program. There is a need to revisit the FNC program by the type of morbidity and duration of stay. Further studies will be required to explore the health system adequacy to implement such programs in hospitals of Nepal.

Trial registration
ISRCTN- 30829654, Registered on May 02, 2017.
Examining barriers to healthcare access and utilization of antenatal care services: evidence from demographic health surveys in sub-Saharan Africa
Authors: Ahinkorah Bright Opoku , Ameyaw Edward Kwabena , Seidu Abdul-Aziz , Odusina Emmanuel Kolawole , Keetile Mpho , Yaya Sanni 
Published: February 2021

Abstract
Background
Antenatal care utilization is one of the means for reducing the high maternal mortality rates in sub-Saharan Africa. This study examined the association between barriers to healthcare access and implementation of the 2016 WHO antenatal care services model among pregnant women seeking antenatal care in selected countries in sub-Saharan Africa.

Methods
This study considered only Demographic and Health Survey data collected in 2018 in sub-Saharan Africa. Hence, the Demographic and Health Survey data of four countries in sub-Saharan Africa (Nigeria, Mali, Guinea and Zambia) were used. A sample of 6761 from Nigeria, 1973 from Mali, 1690 from Guinea and 1570 from Zambia was considered. Antenatal care visits, categorized as < 8 visits or ≥8 visits, and time of the first antenatal care visit, categorized as ≤3 months or > 3 months (as per the WHO recommendations) were the outcome variables for this study. Both descriptive statistics and ordinal logistic regression were used to analyze the data. Crude odds ratios (cOR) and adjusted odds ratios (aOR) and p-values < 0.05 were used for the interpretation of results.

Results
With timing of antenatal care visits, getting money needed for treatment (aOR = 1.38, 95% CI = 1.03–1.92) influenced early timing of antenatal care visits in Mali whereas getting permission to visit the health facility (aOR = 1.62, 95% CI = 1.15–2.33) motivated women to have early timing of antenatal care visits in Guinea. We found that women who considered getting money needed for treatment as not a big problem in Nigeria were more likely to have the recommended number of antenatal care visits (aOR = 1.38, 95% CI= 1.11–1.73). On the contrary, in Guinea, Zambia and Mali, getting permission to visit health facilities, getting money for treatment, distance to the health facility and not wanting to go alone were not barriers to having ≥ 8 antenatal care visits.

Conclusion
Our study has emphasized the role played by barriers to healthcare access in antenatal care utilization across sub-Saharan African countries. There is the need for governmental and non-governmental organizations to ensure that policies geared towards improving the quality of antenatal care and promoting good interaction between health care seekers and health care providers are integrated within the health system.
The mutational landscape of human olfactory G protein-coupled receptors
Authors: Jimenez Ramón Cierco , Casajuana-Martin Nil , García-Recio Adrián , Alcántara Lidia , Pardo Leonardo , Campillo Mercedes , Gonzalez Angel 
Published: February 2021

Abstract
Background
Olfactory receptors (ORs) constitute a large family of sensory proteins that enable us to recognize a wide range of chemical volatiles in the environment. By contrast to the extensive information about human olfactory thresholds for thousands of odorants, studies of the genetic influence on olfaction are limited to a few examples. To annotate on a broad scale the impact of mutations at the structural level, here we analyzed a compendium of 119,069 natural variants in human ORs collected from the public domain.

Results
OR mutations were categorized depending on their genomic and protein contexts, as well as their frequency of occurrence in several human populations. Functional interpretation of the natural changes was estimated from the increasing knowledge of the structure and function of the G protein-coupled receptor (GPCR) family, to which ORs belong. Our analysis reveals an extraordinary diversity of natural variations in the olfactory gene repertoire between individuals and populations, with a significant number of changes occurring at the structurally conserved regions. A particular attention is paid to mutations in positions linked to the conserved GPCR activation mechanism that could imply phenotypic variation in the olfactory perception. An interactive web application (hORMdb, Human Olfactory Receptor Mutation Database) was developed for the management and visualization of this mutational dataset.

Conclusion
We performed topological annotations and population analysis of natural variants of human olfactory receptors and provide an interactive application to explore human OR mutation data. We envisage that the utility of this information will increase as the amount of available pharmacological data for these receptors grow. This effort, together with ongoing research in the study of genetic changes in other sensory receptors could shape an emerging sensegenomics field of knowledge, which should be considered by food and cosmetic consumer product manufacturers for the benefit of the general population.
Immunogenicity study of a Streptococcus suis autogenous vaccine in preparturient sows and evaluation of passive maternal immunity in piglets
Authors: Corsaut Lorelei , Martelet Léa , Goyette-Desjardins Guillaume , Beauchamp Guy , Denicourt Martine , Gottschalk Marcelo , Segura Mariela 
Published: February 2021

Abstract
Background
Streptococcus suis is an important pathogen that causes severe diseases mostly in weaned piglets. Only available vaccines in the field are those composed of killed bacteria (bacterins) but data about their effectiveness are missing. We report here a field study on the immunological response induced by an autogenous vaccine applied in pre-parturient sows. Using a farm with recurrent S. suis serotype 7 problems, the study was divided in three experiments: (I) Sows received the vaccine at 7 and 3 weeks pre-farrowing. (II) Replacement gilts introduced to the herd received the vaccine at 4 and 7 weeks after their entry in quarantine and a boost 3 weeks pre-farrowing. (III) Gilts from experiment II received another boost 3 weeks pre-farrowing at their 3rd/4th parity. Levels, isotype profile and opsonophagocytosis capacity of the serum antibodies induced by vaccination were evaluated in sows and maternal immunity in piglets.

Results
In sows (I), the vaccine induced a slight, albeit significant, increase in anti-S. suis total antibodies after 2 doses when compare to basal levels already present in the animals. These antibodies showed a high opsonic capacity in vitro, highlighting their potential protective capacity. A gilt vaccination program of 3 doses (II) resulted in a significant increase in anti-S. suis total antibodies. Levels of maternal immunity transferred to piglets were high at 7 days of age, but rapidly decreased by 18 days of age. A gilt vaccination program ensued a higher transfer of maternal immunity in piglets compared to control animals; nevertheless duration was not improved at 18 day-old piglets. The vaccine response in both gilts and sows was mainly composed of IgG1 subclass, which was also the main Ig transferred to piglets. IgG2 subclass was also found in piglets, but its level was not increased by vaccination. Finally, a recall IgG1 response was induced by another boost vaccination at 3rd/4th parity (III), indicating that the vaccine induced the establishment of a lasting memory response in the herd.

Conclusions
Overall, an optimal gilt/sow vaccination program might result in increased antibody responses; nevertheless duration of maternal immunity would not last long enough to protect post-weaned piglets.
Production of succinate by engineered strains of Synechocystis PCC 6803 overexpressing phosphoenolpyruvate carboxylase and a glyoxylate shunt
Authors: Durall Claudia , Kukil Kateryna , Hawkes Jeffrey A. , Albergati Alessia , Lindblad Peter , Lindberg Pia 
Published: February 2021

Abstract
Background
Cyanobacteria are promising hosts for the production of various industrially important compounds such as succinate. This study focuses on introduction of the glyoxylate shunt, which is naturally present in only a few cyanobacteria, into Synechocystis PCC 6803. In order to test its impact on cell metabolism, engineered strains were evaluated for succinate accumulation under conditions of light, darkness and anoxic darkness. Each condition was complemented by treatments with 2-thenoyltrifluoroacetone, an inhibitor of succinate dehydrogenase enzyme, and acetate, both in nitrogen replete and deplete medium.

Results
We were able to introduce genes encoding the glyoxylate shunt, aceA and aceB, encoding isocitrate lyase and malate synthase respectively, into a strain of Synechocystis PCC 6803 engineered to overexpress phosphoenolpyruvate carboxylase. Our results show that complete expression of the glyoxylate shunt results in higher extracellular succinate accumulation compared to the wild type control strain after incubation of cells in darkness and anoxic darkness in the presence of nitrate. Addition of the inhibitor 2-thenoyltrifluoroacetone increased succinate titers in all the conditions tested when nitrate was available. Addition of acetate in the presence of the inhibitor further increased the succinate accumulation, resulting in high levels when phosphoenolpyruvate carboxylase was overexpressed, compared to control strain. However, the highest succinate titer was obtained after dark incubation of an engineered strain with a partial glyoxylate shunt overexpressing isocitrate lyase in addition to phosphoenolpyruvate carboxylase, with only 2-thenoyltrifluoroacetone supplementation to the medium.

Conclusions
Heterologous expression of the glyoxylate shunt with its central link to the tricarboxylic acid cycle (TCA) for acetate assimilation provides insight on the coordination of the carbon metabolism in the cell. Phosphoenolpyruvate carboxylase plays an important role in directing carbon flux towards the TCA cycle.
LiCl induces apoptosis via CHOP/NOXA/Mcl-1 axis in human choroidal melanoma cells
Authors: Zhang Qiuqiu , Zhang Qianwei , Li Huiyuan , Zhao Xiaofei , Zhang Han 
Published: February 2021

Abstract
Background
Choroidal melanoma is the most common primary intraocular malignancy that occurs in adults. Lithium Chloride Promotes Apoptosis in Human Leukemia NB4 Cells by Inhibiting Glycogen Synthase Kinase-3 Beta. In this study, we aimed to understand whether LiCl exerts anticancer effects on choroidal melanoma cells and elucidate the underlying molecular mechanisms.

Methods
Human choroidal melanoma cells were treated with LiCl, and cell survival was assessed with MTT assays. Cell reproductive viability was measured by plate colony formation assays. Cell apoptosis was evaluated using flow cytometry, and proteins were detected using western blotting. A human choroidal melanoma xenograft model was established to demonstrate the effect of LiCl on human choroidal melanoma in vivo.

Results
We found that LiCl inhibited cell survival and clonogenic potential and induced apoptosis in human choroidal melanoma cells. LiCl also reduced the proliferation of choroidal melanoma cells in vivo. Moreover, the upregulation of NOXA and downregulation of Mcl-1 were responsible for LiCl-induced apoptosis. Mcl-1 overexpression obviously impaired LiCl-induced apoptosis and cleavage of caspase8, caspase9, caspase3 and PARP. Moreover, the protein expression of endoplasmic reticulum stress markers, including IRE1α, Bip, p-eIF2α, ATF4 and CHOP, were upregulated following treatment with LiCl. When CHOP expression was knocked down and cells were treated with LiCl, the protein level of NOXA was partially increased, and Mcl-1 expression was increased, while the cleavage of caspase8, caspase9, caspase3 and PARP that was induced by the LiCl was reduced compared with the vehicle treated group. Prolonged ER stress results in the activation of the apoptotic pathway.

Conclusions
In summary, LiCl induced an endoplasmic reticulum stress response while activating intrinsic apoptosis. Furthermore, the CHOP/NOXA/Mcl-1 axis contributed to LiCl-induced apoptosis both in vitro and in vivo. The present study provides important mechanistic insight into potential cancer treatments involving LiCl and enhances the understanding of human choroidal melanoma.
The lncRNA NEAT1 promotes the epithelial-mesenchymal transition and metastasis of osteosarcoma cells by sponging miR-483 to upregulate STAT3 expression
Authors: Chen Yan , Li Jun , Xiao Jia-Kun , Xiao Lei , Xu Bin-Wu , Li Chen 
Published: February 2021

AbstractBackgroundOsteosarcoma is one of the most prevalent primary bone tumours in adolescents. Accumulating evidence shows that aberrant expression of the long non-coding RNA (lncRNA) NEAT1 and microRNA-483 (miR-483) contribute to the epithelial-mesenchymal transition (EMT), invasion and metastasis of tumour cells. However, the potential regulatory effects of NEAT1 and miR-483 on the EMT of osteosarcoma remain elusive.MethodsThe expression of the NEAT1, miR-483, signal transducer and activator of transcription-1 (STAT1), STAT3, and EMT-associated markers was measured using qRT-PCR or western blotting. NEAT1 overexpression or knockdown was induced by lentivirus-mediated transfection. A luciferase reporter assay was employed to confirm the association between NEAT1/miR-483 and miR-483/STAT3. RNA immunoprecipitation (RIP) was also performed to verify the NEAT1 and miR-483 interaction. Wound healing and transwell assays were implemented to assess the migration and invasion of U2OS cells. Unilateral subcutaneous injection of U2OS into nude mice was performed to investigate tumour metastasis in vivo.ResultsThe expression of miR-483 was downregulated in both osteosarcoma cell lines and osteosarcoma tissues. The overexpression of miR-483 suppressed the migration, invasion, and expression of EMT-associated proteins in U2OS cells, while simultaneous overexpression of STAT3 partially relieved this suppression. Mechanistically, miR-483 specifically targeted the 3′ untranslated region (3′UTR) of STAT3 and repressed its expression. However, NEAT1 sponged miR-438, increased STAT3 expression, and repressed STAT1 expression, subsequently increasing the EMT of osteosarcoma cells. The knockdown of NEAT1 in transplanted U2OS cells impaired the liver and lung metastases of osteosarcoma in nude mice. Moreover, NEAT1 silencing inhibited the mesenchymal- epithelial transition (MET) of osteosarcoma at metastasis sites.ConclusionsThe lncRNA NEAT1/miR-483/STAT3 axis plays a crucial role in regulating the metastasis of osteosarcoma and potentially represents one appealing therapeutic target for osteosarcoma treatment in the future.
M2 macrophages‐derived exosomal microRNA-501-3p promotes the progression of lung cancer via targeting WD repeat domain 82
Authors: Lei Jie , Chen Peng , Zhang Feng , Zhang Na , Zhu Jianfei , Wang Xiaoping , Jiang Tao 
Published: February 2021

Abstract
Background
Exosomes are known to transmit microRNAs (miRNAs) to affect cancer progression, while the role of M2 macrophages-derived exosomes (M2 exosomes) conveying miR-501-3p in lung cancer (LC) remains unknown. We aim to explore the role of exosomal miR-501-3p in LC development via targeting WD repeat domain 82 (WDR82).

Methods
Lung cancer tissue and normal tissue specimens were collected, in which tumor-associated macrophages (TAM) were measured by immunohistochemistry. M2 macrophages were induced and treated with altered miR-501-3p, and then the exosomes were extracted and identified. MiR-501-3p and WDR82 expression in LC tissues and cell liens was determined. The predictive role of miR-501-3p in prognosis of LC patients was assessed, and the proliferation, colony formation ability, invasion, migration and apoptosis of the LC cells were determined. Targeting relationship between miR-501-3p and WDR82 was confirmed.

Results
TAM level was elevated in lung cancer tissues. MiR-501-3p was upregulated while WDR82 was downregulated in LC tissues and cell lines, and the M2 exosomes further upregulated miR-501-3p. M2 exosomes and exosomal miR-501-3p promoted LC cell growth. MiR-501-3p inhibition reversed the effect of M2 exosomes on LC cells. WDR82 was confirmed as a target gene of miR-501-3p.

Conclusion
M2 macrophages-derived exosomal miR-501-3p promotes the progression of LC via downregulating WDR82.