bluuebunny/crossref_metadata_2025 huggingface dataset:
The burden of waiting to access pain clinic services: perceptions and experiences of patients with rheumatic conditions
Authors: Deslauriers Simon , Roy Jean-Sébastien , Bernatsky Sasha , Blanchard Nathan , Feldman Debbie E. , Pinard Anne Marie , Fitzcharles Mary-Ann , Desmeules François , Perreault Kadija
Published: February 2021

Background

Extensive waiting times before receiving services is a major barrier to adequate pain management. Waiting times may have a detrimental impact on patients’ conditions and quality of life. However, there remains a lack of knowledge on the actual experiences of patients waiting to receive services, especially for those with rheumatic conditions. The present study aimed to gain an in-depth understanding of perceptions and experiences of patients with rheumatic conditions regarding access to pain clinic services. The secondary objective was to identify possible solutions to improve this access according to patients’ perspectives.

Methods

This qualitative study based on semi-structured interviews was conducted with adults with rheumatic conditions waiting to access pain clinics in the province of Quebec, Canada. Interviews were transcribed verbatim and analyzed using thematic content analysis.

Results

Twenty-six participants were interviewed (22 women and 4 men; mean age 54 ± 10 years). Four main themes were identified: 1) the perception that waiting time is unacceptably long; 2) how the lack of information affects patients’ experiences of waiting; 3) patients’ various expectations towards the pain clinic, from high hopes to disillusionment and 4) carrying an emotional, physical and financial burden resulting from the wait. Participants reported several solutions to improve the experience of waiting, including providing information to patients, increasing resources, improving prioritization processes and care coordination, and providing alternative interventions to patients during the wait.

Conclusions

For patients with rheumatic conditions, access to pain clinic services is challenging due to extensive waiting times. The burden it imposes on them adds to the existing challenge of living with a chronic rheumatic condition. The solutions identified by participants could serve as building blocks to develop and implement measures to improve patients’ experience of accessing pain-related services.
Personalized genealogical history of UK individuals inferred from biobank-scale IBD segments
Authors: Naseri Ardalan , Tang Kecong , Geng Xin , Shi Junjie , Zhang Jing , Shakya Pramesh , Liu Xiaoming , Zhang Shaojie , Zhi Degui
Published: February 2021

Background

The genealogical histories of individuals within populations are of interest to studies aiming both to uncover detailed pedigree information and overall quantitative population demographic histories. However, the analysis of quantitative details of individual genealogical histories has faced challenges from incomplete available pedigree records and an absence of objective and quantitative details in pedigree information. Although complete pedigree information for most individuals is difficult to track beyond a few generations, it is possible to describe a person’s genealogical history using their genetic relatives revealed by identity by descent (IBD) segments—long genomic segments shared by two individuals within a population, which are identical due to inheritance from common ancestors. When modern biobanks collect genotype information for a significant fraction of a population, dense genetic connections of a person can be traced using such IBD segments, offering opportunities to characterize individuals in the context of the underlying populations. Here, we conducted an individual-centric analysis of IBD segments among the UK Biobank participants that represent 0.7% of the UK population.

Results

We made a high-quality call set of IBD segments over 5 cM among all 500,000 UK Biobank participants. On average, one UK individual shares IBD segments with 14,000 UK Biobank participants, which we refer to as “relatives.” Using these segments, approximately 80% of a person’s genome can be imputed. We subsequently propose genealogical descriptors based on the genetic connections of relative cohorts of individuals sharing at least one IBD segment and show that such descriptors offer important information about one’s genetic makeup, personal genealogical history, and social behavior. Through analysis of relative counts sharing segments at different lengths, we identified a group, potentially British Jews, who has a distinct pattern of familial expansion history. Finally, using the enrichment of relatives in one’s neighborhood, we identified regional variations of personal preference favoring living closer to one’s extended families.

Conclusions

Our analysis revealed genetic makeup, personal genealogical history, and social behaviors at the population scale, opening possibilities for further studies of individual’s genetic connections in biobank data.
Sustained CHK2 activity, but not ATM activity, is critical to maintain a G1 arrest after DNA damage in untransformed cells
Authors: García-Santisteban Iraia , Llopis Alba , Krenning Lenno , Vallejo-Rodríguez Jon , van den Broek Bram , Zubiaga Ana M. , Medema René H.
Published: February 2021

Background

The G1 checkpoint is a critical regulator of genomic stability in untransformed cells, preventing cell cycle progression after DNA damage. DNA double-strand breaks (DSBs) recruit and activate ATM, a kinase which in turn activates the CHK2 kinase to establish G1 arrest. While the onset of G1 arrest is well understood, the specific role that ATM and CHK2 play in regulating G1 checkpoint maintenance remains poorly characterized.

Results

Here we examine the impact of ATM and CHK2 activities on G1 checkpoint maintenance in untransformed cells after DNA damage caused by DSBs. We show that ATM becomes dispensable for G1 checkpoint maintenance as early as 1 h after DSB induction. In contrast, CHK2 kinase activity is necessary to maintain the G1 arrest, independently of ATM, ATR, and DNA-PKcs, implying that the G1 arrest is maintained in a lesion-independent manner. Sustained CHK2 activity is achieved through auto-activation and its acute inhibition enables cells to abrogate the G1-checkpoint and enter into S-phase. Accordingly, we show that CHK2 activity is lost in cells that recover from the G1 arrest, pointing to the involvement of a phosphatase with fast turnover.

Conclusion

Our data indicate that G1 checkpoint maintenance relies on CHK2 and that its negative regulation is crucial for G1 checkpoint recovery after DSB induction.
Dynamic meta-analysis: a method of using global evidence for local decision making
Authors: Shackelford Gorm E. , Martin Philip A. , Hood Amelia S. C. , Christie Alec P. , Kulinskaya Elena , Sutherland William J.
Published: February 2021

Background

Meta-analysis is often used to make generalisations across all available evidence at the global scale. But how can these global generalisations be used for evidence-based decision making at the local scale, if the global evidence is not perceived to be relevant to local decisions? We show how an interactive method of meta-analysis—dynamic meta-analysis—can be used to assess the local relevance of global evidence.

Results

We developed Metadataset (www.metadataset.com) as a proof-of-concept for dynamic meta-analysis. Using Metadataset, we show how evidence can be filtered and weighted, and results can be recalculated, using dynamic methods of subgroup analysis, meta-regression, and recalibration. With an example from agroecology, we show how dynamic meta-analysis could lead to different conclusions for different subsets of the global evidence. Dynamic meta-analysis could also lead to a rebalancing of power and responsibility in evidence synthesis, since evidence users would be able to make decisions that are typically made by systematic reviewers—decisions about which studies to include (e.g. critical appraisal) and how to handle missing or poorly reported data (e.g. sensitivity analysis).

Conclusions

In this study, we show how dynamic meta-analysis can meet an important challenge in evidence-based decision making—the challenge of using global evidence for local decisions. We suggest that dynamic meta-analysis can be used for subject-wide evidence synthesis in several scientific disciplines, including agroecology and conservation biology. Future studies should develop standardised classification systems for the metadata that are used to filter and weight the evidence. Future studies should also develop standardised software packages, so that researchers can efficiently publish dynamic versions of their meta-analyses and keep them up-to-date as living systematic reviews. Metadataset is a proof-of-concept for this type of software, and it is open source. Future studies should improve the user experience, scale the software architecture, agree on standards for data and metadata storage and processing, and develop protocols for responsible evidence use.
The impact of local and national restrictions in response to COVID-19 on social contacts in England: a longitudinal natural experiment
Authors:   CMMID COVID-19 working group, Jarvis Christopher I. , Gimma Amy , van Zandvoort Kevin , Wong Kerry L. M. , Edmunds W. John
Published: February 2021

Background

England’s COVID-19 response transitioned from a national lockdown to localised interventions. In response to rising cases, these were supplemented by national restrictions on contacts (the Rule of Six), then 10 pm closing for bars and restaurants, and encouragement to work from home. These were quickly followed by a 3-tier system applying different restrictions in different localities. As cases continued to rise, a second national lockdown was declared. We used a national survey to quantify the impact of these restrictions on epidemiologically relevant contacts.

Methods

We compared paired measures on setting-specific contacts before and after each restriction started and tested for differences using paired permutation tests on the mean change in contacts and the proportion of individuals decreasing their contacts.

Results

Following the imposition of each measure, individuals tended to report fewer contacts than they had before. However, the magnitude of the changes was relatively small and variable. For instance, although early closure of bars and restaurants appeared to have no measurable effect on contacts, the work from home directive reduced mean daily work contacts by 0.99 (95% confidence interval CI] 0.03–1.94), and the Rule of Six reduced non-work and school contacts by a mean of 0.25 (0.01–0.5) per day. Whilst Tier 3 appeared to also reduce non-work and school contacts, the evidence for an effect of the lesser restrictions (Tiers 1 and 2) was much weaker. There may also have been some evidence of saturation of effects, with those who were in Tier 1 (least restrictive) reducing their contacts markedly when they entered lockdown, which was not reflected in similar changes in those who were already under tighter restrictions (Tiers 2 and 3).

Conclusions

The imposition of various local and national measures in England during the summer and autumn of 2020 has gradually reduced contacts. However, these changes are smaller than the initial lockdown in March. This may partly be because many individuals were already starting from a lower number of contacts.
Prevalence of bovine abortion, calf mortality, and bovine viral diarrhea virus (BVDV) persistently infected calves among pastoral, peri-urban, and mixed-crop livestock farms in central and Northwest Ethiopia
Authors: Yitagesu Erdachew , Jackson Wendi , Kebede Nigatu , Smith Woutrina , Fentie Tsegaw
Published: February 2021

Background

Bovine Viral Diarrhea virus (BVDV) is one of important diseases of cattle worldwide causing economic losses to the cattle industry primarily due to increased premature culling and decreased reproductive performance. The virus can cross the placenta during early pregnancy and result in the birth of persistently infected (PI) calves that are efficient transmitters of BVDV and serving as the primary reservoirs for BVDV. Relatively few studies have focused on understanding BVDV seroprevalence, virus detection, genotyping and its distribution in Africa. Most BVDV research in Ethiopia has involved serologic surveys in adult cattle, rather than the identification of PI calves, despite their role in viral shedding and recurring infections. A cross-sectional study was undertaken in three different livestock production systems of Ethiopia with the objective to estimate the prevalence of bovine abortion, calf mortality, and BVDV persistently infected calves.

Results

Ear notch samples (882) collected from calves in 349 households were tested for BVDV antigen using antigen capture enzyme-linked immunosorbent assay (ACE). All samples tested were negative for BVDV antigen. The overall animal level crude abortion and calf mortality prevalence were 4.0% (95% CI: 2.9–5.2) and 9.2% (95% CI: 7.7–11.0) respectively. The lower BVDV PI prevalence may be due to a lower effective contact rate between cattle reared in small-scale extensive production systems in Ethiopia.

Conclusions

This is the first report of BVDV Ag test in Ethiopia and no PI was detected in calves in the study areas. Since BVDV is a disease of great economic importance, this study finding must be interpreted with care since absence of evidence is not evidence of absence and even a single BVDV infected animal can serve as source of infection and contribute to the persistent spread of the virus. Greater attention needs to be given to screening for PI animals through testing large number of animals and culling positive animals. Hence, future research should focus on regions and production systems with high BVDV seroprevalence followed by antigen ELISA or BVDV real-time PCR to detect persistently infected and acutely viremic animals.
Discovery and validation of FBLN1 and ANT3 as potential biomarkers for early detection of cervical cancer
Authors: Hao Yi , Ye Ming , Chen Xiaona , Zhao Hongli , Hasim Ayshamgul , Guo Xia
Published: February 2021

Background

To validate markers for cervical carcinoma (CC) and precancerous lesions related with HPV infections.

Methods

Three different cervical cancer cell lines C-33A, SiHa and Caski were used for secretome profiling by label-free quantitative proteomics. Cervical exfoliated cells and matching serum samples were collected from 284 patients with normal control (n = 75, 26.41 %), precancerous lesions (n = 88, 30.99 %) and early stage cervical squamous carcinoma (n = 121, 42.61 %). HPV subtyping and quantification was performed by PCR and hybridization. 20 candidate proteins identified in previous screening studies (tissue, plasma, cells) were quantified by ELISA. Finally, highly quantitative parallel reaction monitoring mass spectrometry was used to assess the specificities and sensitivities of candidate serum markers.

Results

While CC was found to be associated with high-risk HPV subtypes, serum antibodies for high risk HPV were not significantly related to the progression of cervical cancer. Significant differences between patient groups were detected for the four proteins CLU, APOA4, APOE and MLH3, but none would allow clinical application due to insufficient sensitivity and specificity and large variability. Subsequent proteomic secretome analysis of cervical cancer cell lines identified a set of 729 common proteins. Cross referencing this dataset with ELISA measurements revealed six candidate proteins of which two, FBLN1 and ANT3, showed co-occurrence with HPV infection (75.7 % and 85 %, respectively) and had promising diagnostic ability in terms of sensitivity and specificity. After the loss of E6/E7 by using CRISPR/Cas9 gene editing, the content of ANT3 and FBLN1 in KoE6/E7 SiHa were downregulated, which indicated the expression of ANT3 and FBLN1 in cervical cancer may be affected by HPV infection.

Conclusions

FBLN1 and ANT3 might be potential tumor- and HPV-associated serum markers.
Ring finger protein 152-dependent degradation of TSPAN12 suppresses hepatocellular carcinoma progression
Authors: Wan Jian , Liu Shunfang , Sun Wanju , Yu Haiyi , Tang Wenlian , Liu Wei , Ji Jing , Liu Bin
Published: February 2021

Background

Hepatocellular carcinoma (HCC) is the third cause of cancer death in the world, and few molecularly targeted anticancer therapies have been developed to treat it. The E3 ubiquitin ligase RNF152 has been reported to regulate the activity of the mechanistic target of rapamycin complex 1 (mTORC1), induce autophagy and apoptosis. However, the relationship between RNF152 and HCC is unclear.

Methods

Transcriptome RNA-sequencing data of HCC samples and normal tissues were used to detect the mRNA expression of RNF152. Luciferase reporter and chromatin immunoprecipitation (ChIP) assays were used to determine the transcriptional regulation of RNF152 in HCC by FoxO1. RNAi, cell proliferation, colony formation and transwell assays were used to determine the in vitro functions of RNF152. Mouse xenograft models were used to study the in vivo effects of RNF152. The immunoprecipitation assay was used to determine the interaction between RNF152 and TSPAN12. The in vivo ubiquitination assay was performed to determine the regulation of TSPAN12 by RNF152.

Results

We found that RNF152 is significantly down-regulated in clinic HCC samples, and its down-regulation is associated with pool overall survival (OS), progression-free survival (PFS) and disease-specific survival (DSS) in HCC patients. The transcription factor FoxO1 was significantly positively correlated RNF152 expression in HCC tissues. FoxO1 recognizes a classic insulin response element (IRE) on the RNF152 promoter to regulate its expression in HCC. RNF152 suppressed HCC cell proliferation, clonogenic survival, invasion in vitro, and tumorigenesis in vivo. Mechanistically, RNF152 interacted with TSPAN12 and targeted it for ubiquitination and proteasomal degradation, thereby inhibiting TSPAN12-dependent CXCL6 expression and HCC progression.

Conclusion

Collectively, our data revealed a tumor suppressor role of RNF152 and a connection between RNF152 and FoxO1 in HCC. Our results support an important role of the FoxO1-RNF152-TSPAN12 axis in the development of HCC. Therapeutic targeting this axis may be an effective means of treating HCC.
Identification of four genes and biological characteristics of esophageal squamous cell carcinoma by integrated bioinformatics analysis
Authors: Song Yexun , Wang Xianyao , Wang Fengjun , Peng Xiaowei , Li Peiyu , Liu Shaojun , Zhang Decai
Published: February 2021

Background

Esophageal squamous cell carcinoma (ESCC) has become one of the most serious diseases affecting populations worldwide and is the primary subtype of esophageal cancer (EC). However, the molecular mechanisms governing the development of ESCC have not been fully elucidated.

Methods

The robust rank aggregation method was performed to identify the differentially expressed genes (DEGs) in six datasets (GSE17351, GSE20347, GSE23400, GSE26886, GSE38129 and GSE77861) from the Gene Expression Omnibus (GEO). The Search Tool for the Retrieval of Interacting Genes (STRING) database was utilized to extract four hub genes from the protein–protein interaction (PPI) network. Module analysis and disease free survival analysis of the four hub genes were performed by Cytoscape and GEPIA. The expression of hub genes was analyzed by GEPIA and the Oncomine database and verified by real-time quantitative PCR (qRT-PCR).

Results

In total, 720 DEGs were identified in the present study; these genes consisted of 302 upregulated genes and 418 downregulated genes that were significantly enriched in the cellular component of the extracellular matrix part followed by the biological process of the cell cycle phase and nuclear division. The primary enriched pathways were hsa04110:Cell cycle and hsa03030:DNA replication. Four hub genes were screened out, namely, SPP1, MMP12, COL10A1 and COL5A2. These hub genes all exhibited notably increased expression in ESCC samples compared with normal samples, and ESCC patients with upregulation of all four hub genes exhibited worse disease free survival.

Conclusions

SPP1, MMP12, COL10A1 and COL5A2 may participate in the tumorigenesis of ESCC and demonstrate the potential to serve as molecular biomarkers in the early diagnosis of ESCC. This study may help to elucidate the molecular mechanisms governing ESCC and facilitate the selection of targets for early treatment and diagnosis.
The immune‐related biomarker TEK inhibits the development of clear cell renal cell carcinoma (ccRCC) by regulating AKT phosphorylation
Authors: Chen Siming , Yu Mengxue , Ju Lingao , Wang Gang , Qian Kaiyu , Xiao Yu , Wang Xinghuan
Published: February 2021

Background

High immunogenicity is an important feature of ccRCC, but its underlying immune-related molecular mechanisms remain unclear. This study aimed to investigate the effect of immune-related gene TEK on ccRCC and its prognostic value.

Methods

The immune-related differentially expressed genes (DEGs) and transcription factors (TFs) in ccRCC were screened based on The Cancer Genome Atlas (TCGA) database, and a regulatory network of TF was constructed. Prognostic-related immune genes were screened by univariate Cox regression analysis and functional annotation was performed. Univariate and multivariate Cox regression analyses were performed to construct the immune gene risk model and identify the hub gene TEK that independently affected the prognosis of ccRCC. The effectiveness of the TEK was verified by external microarray datasets. The relationship between TEK and immune cells in ccRCC was evaluated based on Tumor Immune Estimation Resource (TIMER). The expression of TEK in clinical specimens was verified by qRT-PCR and immunohistochemical (IHC) staining. MTT and cloning formation assay were used to evaluate cell proliferation. Transwell assays were used to assess cell migration. Apoptosis was assessed by flow cytometry, and the expression of related proteins was detected by Western blot and immunofluorescence.

Results

We constructed a prognostic model consisting of 12 hub genes and performed risk scores to determine the relationship between these scores and prognosis. Through Cox regression analysis and survival analysis, TEK, an immune marker highly related to survival prognosis, was obtained and validated.In vitroexperiments showed that knockdown ofTEKpromoted the proliferation and migration of ccRCC cells, and we found that TEK promoted apoptosis by regulating the phosphorylation of AKT, thereby inhibiting cell proliferation.

Conclusions

TEK plays an important role in risk assessment and survival prediction for ccRCC patients as a new immune gene and maybe an emerging target for immunotherapy for ccRCC patients.
Evaluation of the durability and use of long‐lasting insecticidal nets in Nicaragua
Authors: Villalta Emperatriz Lugo , Soto Bravo Aida Mercedes , Vizcaino Lucrecia , Dzuris Nicole , Delgado Marco , Green Michael , Smith Stephen C. , Lenhart Audrey , Macedo de Oliveira Alexandre
Published: February 2021

Background

Vector control for malaria prevention relies most often on the use of insecticide-treated bed net (ITNs) and indoor residual spraying. Little is known about the longevity of long-lasting insecticidal nets (LLINs) in the Americas. The physical integrity and insecticide retention of LLINs over time were monitored after a bed net distribution campaign to assess community practices around LLIN care and use in Waspam, northeastern Nicaragua.

Methods

At least 30 nets were collected at 6, 12, 24, and 36 months post distribution. Physical integrity was measured by counting holes and classifying nets into categories (good, damaged, and too torn) depending on a proportionate hole index (pHI). Insecticide bioefficacy was assessed using cone bioassays, and insecticide content measured using a cyanopyrethroid field test (CFT).

Results

At 6 months, 87.3 % of LLINs were in good physical condition, while by 36 months this decreased to 20.6 %, with 38.2 % considered ‘too torn.’ The median pHI increased from 7 at the 6-month time point to 480.5 by 36 months. After 36 months of use, median mortality in cone bioassays was 2 % (range: 0–6 %) compared to 16 % (range: 2–70 %) at 6 months. There was a decrease in the level of deltamethrin detected on the surface of the LLINs with 100 % of tested LLINs tested at 12 months and 24 months crossing the threshold for being considered a failed net by CFT.

Conclusions

This first comprehensive analysis of LLIN durability in Central America revealed rapid loss of chemical bioefficacy and progressive physical damage over a 36-month period. Use of these findings to guide future LLIN interventions in malaria elimination settings in Nicaragua, and potentially elsewhere in the Americas, could help optimize the successful implementation of vector control strategies.
Genomic investigation of atypical malaria cases in Kanel, northern Senegal
Authors: Sy Mouhamad , Badiane Aida Sadikh , Deme Awa Bineta , Gaye Amy , Ndiaye Tolla , Fall Fatou Ba , Siddle Katherine J. , Dieye Baba , Ndiaye Yaye Die , Diallo Mamadou Alpha , Diongue Khadim , Seck Mame Cheikh , Ndiaye Ibrahima Mbaye , Cissé Moustapha , Gueye Alioune Badara , Sène Doudou , Dieye Yakou , Souané Tamba , MacInnis Bronwyn , Volkman Sarah K. , Wirth Dyann F. , Ndiaye Daouda
Published: February 2021

Background

The diagnosis of malaria cases in regions where the malaria burden has decreased significantly and prevalence is very low is more challenging, in part because of reduced clinical presumption of malaria. The appearance of a cluster of malaria cases with atypical symptoms in Mbounguiel, a village in northern Senegal where malaria transmission is low, in September 2018 exemplifies this scenario. The collaboration between the National Malaria Control Programme (NMCP) at the Senegal Ministry of Health and the Laboratory of Parasitology and Mycology at Cheikh Anta Diop University worked together to evaluate this cluster of malaria cases using molecular and serological tools.

Methods

Malaria cases were diagnosed primarily by rapid diagnostic test (RDT), and confirmed by photo-induced electron transfer-polymerase chain reaction (PET-PCR). 24 single nucleotide polymorphisms (SNPs) barcoding was used for Plasmodium falciparum genotyping. Unbiased metagenomic sequencing and Luminex-based multi-pathogen antibody and antigen profiling were used to assess exposure to other pathogens.

Results

Nine patients, of 15 suspected cases, were evaluated, and all nine samples were found to be positive for P. falciparum only. The 24 SNPs molecular barcode showed the predominance of polygenomic infections, with identifiable strains being different from one another. All patients tested positive for the P. falciparum antigens. No other pathogenic infection was detected by either the serological panel or metagenomic sequencing.

Conclusions

This work, undertaken locally within Senegal as a collaboration between the NMCP and a research laboratory at University of Cheikh Anta Diop (UCAD) revealed that a cluster of malaria cases were caused by different strains of P. falciparum. The public health response in real time demonstrates the value of local molecular and genomics capacity in affected countries for disease control and elimination.
Ecology of asynchronous asexual replication: the intraerythrocytic development cycle of Plasmodium berghei is resistant to host rhythms
Authors: O’Donnell Aidan J. , Reece Sarah E.
Published: February 2021

Background

Daily periodicity in the diverse activities of parasites occurs across a broad taxonomic range. The rhythms exhibited by parasites are thought to be adaptations that allow parasites to cope with, or exploit, the consequences of host activities that follow daily rhythms. Malaria parasites (Plasmodium) are well-known for their synchronized cycles of replication within host red blood cells. Whilst most species ofPlasmodiumappear sensitive to the timing of the daily rhythms of hosts, and even vectors, some species present no detectable rhythms in blood-stage replication. Why the intraerythrocytic development cycle (IDC) of, for examplePlasmodium chabaudi,is governed by host rhythms, yet seems completely independent of host rhythms inPlasmodium berghei,another rodent malaria species, is mysterious.

Methods

This study reports a series of five experiments probing the relationships between the asynchronous IDC schedule ofP. bergheiand the rhythms of hosts and vectors by manipulating host time-of-day, photoperiod and feeding rhythms.

Results

The results reveal that: (i) a lack coordination between host and parasite rhythms does not impose appreciable fitness costs onP. berghei; (ii) the IDC schedule ofP. bergheiis impervious to host rhythms, including altered photoperiod and host-feeding-related rhythms; (iii) there is weak evidence for daily rhythms in the density and activities of transmission stages; but (iv), these rhythms have little consequence for successful transmission to mosquitoes.

Conclusions

Overall, host rhythms do not affect the performance ofP. bergheiand its asynchronous IDC is resistant to the scheduling forces that underpin synchronous replication in closely related parasites. This suggests that natural variation in the IDC schedule across species represents different parasite strategies that maximize fitness. Thus, subtle differences in the ecological interactions between parasites and their hosts/vectors may select for the evolution of very different IDC schedules.
Measurement and determinants of catastrophic health expenditure among elderly households in China using longitudinal data from the CHARLS
Authors: Liu Shiai , Coyte Peter C. , Fu Mingqi , Zhang Qilin
Published: February 2021

Background

Catastrophic health expenditure (CHE) among the Chinese elderly warrants attention. However, the incidence, intensity and determinants of CHE have not been fully investigated. This study explores the incidence, intensity and determinants of CHE among elderly Chinese citizens, i.e., those aged 60 years or older.

Methods

Data were obtained from three waves of the China Health and Retirement Longitudinal Study (CHARLS): 2011, 2013 and 2015. The cut-off points used in this study for CHE were 10% of the total expenditures and 40% of non-food expenditure. Under the guidance of Andersen’s model of health services utilization, this study used logistic regression analysis to explore the determinants of CHE.

Results

The incidence of CHE defined as more than 40% of non-food expenditure rose over the study period, 2011–2015, from 20.86% (95% CI: 19.35 to 22.37%) to 31.00% (95% CI: 29.28 to 32.72%). The intensity of CHE also increased. The overshoot (O) based on non-food expenditure rose from 3.12% (95% CI: 2.71 to 3.53%) to 8.75% (95% CI: 8.14 to 9.36%), while the mean positive overshoot (MPO) rose from 14.96% (95% CI: 12.99 to 16.92%) to 28.23% (95% CI: 26.26 to 30.19%). Thus, the problem of CEH was even more serious in 2015 than in 2011. Logistic regression revealed that households were more likely to face CHE if they had a spouse as a household member, reported an inpatient event in the last year, reported an outpatient visit in the last month, were disabled, were members of a poor expenditure quartile, lived in the middle and western zones or resided in an urban area. In contrast, CEH was not significantly affected by respondents being older than 75 years or having a chronic health condition, by household size or by insurance type.

Conclusions

Key policy recommendations include the gradual improvement of medical assistance and the expansion of the use of health insurance to reduce household liability for health expenditures.
Correction to: Exosomes derived from gemcitabine resistant cells transfer malignant phenotypic traits via delivery of miRNA-222-3p
Authors: Wei Feng , Ma Chengyuan , Zhou Tong , Dong Xuechao , Luo Qinghua , Geng Li , Ding Lijuan , Zhang Yandong , Zhang Li , Li Nan , Li Yang , Liu Yan
Published: February 2021

An amendment to this paper has been published and can be accessed via the original article.
Adapting harm reduction services during COVID-19: lessons from the supervised injecting facilities in Australia
Authors: Roxburgh Amanda , Jauncey Marianne , Day Carolyn , Bartlett Mark , Cogger Shelley , Dietze Paul , Nielsen Suzanne , Latimer Julie , Clark Nico
Published: February 2021

The COVID-19 crisis has had profound impacts on health service provision, particularly those providing client facing services. Supervised injecting facilities and drug consumption rooms across the world have been particularly challenged during the pandemic, as have their client group—people who consume drugs. Several services across Europe and North America closed due to difficulties complying with physical distancing requirements. In contrast, the two supervised injecting facilities in Australia (the Uniting Medically Supervised Injecting Centre—MSIC—in Sydney and the North Richmond Community Health Medically Supervised Injecting Room—MSIR—in Melbourne) remained open (as at the time of writing—December 2020). Both services have implemented a comprehensive range of strategies to continue providing safer injecting spaces as well as communicating crucial health information and facilitating access to ancillary services (such as accommodation) and drug treatment for their clients. This paper documents these strategies and the challenges both services are facing during the pandemic. Remaining open poses potential risks relating to COVID-19 transmission for both staff and clients. However, given the harms associated with closing these services, which include the potential loss of life from injecting in unsafe/unsupervised environments, the public and individual health benefits of remaining open are greater. Both services are deemed ‘essential health services’, and their continued operation has important benefits for people who inject drugs in Sydney and Melbourne.
Circ_0082182 promotes oncogenesis and metastasis of colorectal cancer in vitro and in vivo by sponging miR-411 and miR-1205 to activate the Wnt/β-catenin pathway
Authors: Liu Ruijie , Deng Ping , Zhang Yonglian , Wang Yonglan , Peng Cuiping
Published: February 2021

Background

Circular RNAs (circRNAs) are a class of endogenous single-strand RNA transcripts with crucial regulation in human cancers. The objective of this study is to investigate the role of circ_0082182 in CRC and its specific functional mechanism.

Methods

The quantitative real-time polymerase chain reaction (qRT-PCR) was performed to measure the levels of circ_0082182, microRNA-411 (miR-411) and microRNA-1205 (miR-1205). Cell proliferation was detected by Cell counting Kit-8 (CCK-8) and colony formation assays. Flow cytometry was used for determining cell cycle and cell apoptosis. Cell apoptosis was also assessed by caspase3 and caspase9 activities. Cell migration and invasion were examined using scratch assay and transwell assay. The interaction between circ_0082182 and miRNA was validated by the dual-luciferase reporter and biotinylated RNA pull-down assays. Wnt/β-catenin pathway and epithelial-mesenchymal transition (EMT)-associated proteins were quantified by Western blot. Xenograft model was established for the research of circ_0082182 in vivo.

Results

Circ_0082182 was upregulated in CRC and could predict the poor prognosis of CRC patients. Functionally, circ_0082182 promoted CRC cell proliferation, cell cycle progression, and metastasis while inhibited apoptosis. Subsequently, circ_0082182 was shown to act as the sponges of miR-411 and miR-1205. MiR-411 and miR-1205 were identified as tumor inhibitors in CRC. Furthermore, circ_0082182 promoted the CRC progression via sponging miR-411 and miR-1205. Moreover, circ_0082182 facilitated the Wnt/β-catenin pathway and EMT process by targeting miR-411 and miR-1205. In vivo, circ_0082182 accelerated the CRC tumorigenesis and EMT process by activating the Wnt/β-catenin pathway by downregulating the expression of miR-411 or miR-1205.

Conclusion

This study showed that circ_0082182 functioned as an oncogene in the developing process of CRC by sponging miR-411 or miR-1205 to activate the Wnt/β-catenin pathway. Circ_0082182 might be a molecular target in the diagnosis and treatment of CRC.
miR-378a-5p inhibits the proliferation of colorectal cancer cells by downregulating CDK1
Authors: Li Kai , Zhang Jieling , Zhang Mingkang , Wu Yaohua , Lu Xinyu , Zhu Yiping
Published: February 2021

Background

MicroRNAs (miRNAs) play an important role in tumor occurrence. The role of miR-378a-5p and CDK1 in colorectal cancer (CRC) was investigated in this study.

Methods

Investigation of TCGA database and the detection of miR-378a-5p expression in colorectal cancer pathological tissues and colorectal cancer cell lines were undertaken by using qRT-PCR. We performed cell function experiments (CCK-8 assay, EdU assay, colony formation assay, wound healing assay, transwell assay, cell apoptosis assessment, and cell cycle assessment) and nude mouse tumor formation experiments to evaluate the effects of miR-378a-5p on proliferation, metastasis, and invasion to explore the role of miR-378a-5p in vivo and in vitro. Next, through TCGA database, immunohistochemical staining of pathological tissues, and cell function experiments, the role of the target gene CDK1 of miR-378a-5p was verified by database prediction, and dual luciferase reporter gene experiments in colorectal cancer cells were performed. Finally, whether upregulation of CDK1 restores the inhibitory effect of overexpression of miR-378a-5p on the proliferation of CRC cells was studied by overexpression of CDK1.

Results

Bioinformatic analysis showed significant downregulation of miR-378a-5p levels in colorectal cancer (CRC). Cell function experiments and tumor xenograft mouse models confirmed the low expression of miR-378a-5p within CRC tissues, which indicated the tumor suppressive role of miR-378a-5p in CRC. To better explore the regulation of miR-378a-5p in CRC, we predicted and validated cell cycle-dependent protein kinase 1 (CDK1) as the miR-378a-5p target gene and observed that miR-378a-5p suppressed CRC cell proliferation by targeting CDK1.

Conclusion

The results of this study help to elucidate the mechanism by which miR-378a-5p can be used as a tumor marker to inhibit the growth of colorectal cancer and CDK1, which is related to the prognosis of colorectal cancer patients. MiR-378a-5p inhibits CRC cell proliferation by suppressing CDK1 expression, which may become a possible therapeutic target for treatment of CRC.
Possible involvement of neuropeptide and neurotransmitter receptors in Adenomyosis
Authors: Xu Xiaofang , Cai Xianjun , Liu Xishi , Guo Sun-Wei
Published: February 2021

Background

Accumulating data indicate that sensory nerve derived neuropeptides such as substance P and calcitonin gene related-protein (CGRP) can accelerate the progression of endometriosis via their respective receptors, so can agonists to their respective receptors receptor 1 (NK1R), receptor activity modifying protein 1 (RAMP-1) and calcitonin receptor-like receptor (CRLR). Adrenergic β2 receptor (ADRB2) agonists also can facilitate lesional progression. In contrast, women with endometriosis appear to have depressed vagal activity, concordant with reduced expression of α7 nicotinic acetylcholine receptor (α7nAChR). The roles of these receptors in adenomyosis are completely unknown.

Methods

Adenomyotic tissue samples from 30 women with adenomyosis and control endometrial tissue samples from 24 women without adenomyosis were collected and subjected to immunohistochemistry analysis of RAMP1, CRLR, NK1R, ADRB2 and α7nAChR, along with their demographic and clinical information. The extent of tissue fibrosis was evaluated by Masson trichrome staining.

Results

We found that the staining levels of NK1R, CRLR, RAMP1 and ADRB2 were all significantly elevated in adenomyotic lesions as compared with control endometrium. In contrast, α7nAChR staining levels were significantly reduced. The severity of dysmenorrhea correlated positively with lesional ADRB2 staining levels.

Conclusions

Our results suggest that SP, CGRP and noradrenaline may promote, while acetylcholine may stall, the progression of adenomyosis through their respective receptors on adenomyotic lesions. Additionally, through the activation of the hypothalamic-pituitary-adrenal (HPA)-sympatho-adrenal-medullary (SAM) axes and the lesional overexpression of ADRB2, adenomyosis-associated dysmenorrhea and adenomyotic lesions may be mutually promotional, forming a viscous feed-forward cycle.
Combined lymphocyte/monocyte count, D-dimer and iron status predict COVID-19 course and outcome in a long-term care facility
Authors: Biamonte Flavia , Botta Cirino , Mazzitelli Maria , Rotundo Salvatore , Trecarichi Enrico Maria , Foti Daniela , Torti Carlo , Viglietto Giuseppe , Torella Daniele , Costanzo Francesco
Published: February 2021

Background

The Sars-CoV-2 can cause severe pneumonia with multiorgan disease; thus, the identification of clinical and laboratory predictors of the progression towards severe and fatal forms of this illness is needed. Here, we retrospectively evaluated and integrated laboratory parameters of 45 elderly subjects from a long-term care facility with Sars-CoV-2 outbreak and spread, to identify potential common patterns of systemic response able to better stratify patients’ clinical course and outcome.

Methods

Baseline white blood cells, granulocytes’, lymphocytes’, and platelets’ counts, hemoglobin, total iron, ferritin, D-dimer, and interleukin-6 concentration were used to generate a principal component analysis. Statistical analysis was performed by using R statistical package version 4.0.

Results

We identified 3 laboratory patterns of response, renamed as low-risk, intermediate-risk, and high-risk, strongly associated with patients’ survival (p < 0.01). D-dimer, iron status, lymphocyte/monocyte count represented the main markers discriminating high- and low-risk groups. Patients belonging to the high-risk group presented a significantly longer time to ferritin decrease (p: 0.047). Iron-to-ferritin-ratio (IFR) significantly segregated recovered and dead patients in the intermediate-risk group (p: 0.012).

Conclusions

Our data suggest that a combination of few laboratory parameters, i.e. iron status, D-dimer and lymphocyte/monocyte count at admission and during the hospital stay, can predict clinical progression in COVID-19.
Translational stem cell therapy: vascularized skin grafts in skin repair and regeneration
Authors: Phua Qian Hua , Han Hua Alexander , Soh Boon-Seng
Published: February 2021

The skin is made up of a plethora of cells arranged in multiple layers with complex and intricate vascular networks, creating a dynamic microenvironment of cells-to-matrix interactions. With limited donor sites, engineered skin substitute has been in high demand for many therapeutic purposes. Over the years, remarkable progress has occurred in the skin tissue-engineering field to develop skin grafts highly similar to native tissue. However, the major hurdle to successful engraftment is the incorporation of functional vasculature to provide essential nutrients and oxygen supply to the embedded cells. Limitations of traditional tissue engineering have driven the rapid development of vascularized skin tissue production, leading to new technologies such as 3D bioprinting, nano-fabrication and micro-patterning using hydrogel based-scaffold. In particular, the key hope to bioprinting would be the generation of interconnected functional vessels, coupled with the addition of specific cell types to mimic the biological and architectural complexity of the native skin environment. Additionally, stem cells have been gaining interest due to their highly regenerative potential and participation in wound healing. This review briefly summarizes the current cell therapies used in skin regeneration with a focus on the importance of vascularization and recent progress in 3D fabrication approaches to generate vascularized network in the skin tissue graft.
Unanticipated efficacy of SARS-CoV-2 vaccination in older adults
Authors: Pawelec Graham , McElhaney Janet
Published: February 2021

The rapidity with which vaccines against COVID-19 have been developed and tested is unprecedented. As classically the case with randomized clinical trials, many studies excluded older adults. However, given the early realisation that senior citizens were most highly susceptible to COVID, older individuals have been included in licensing trials under these unusual conditions. The recently published results from the Comirnaty Vaccine (BNT162b) trial unexpectedly documented that vaccine efficacy was equally exceptionally high in older and younger adults. These extremely encouraging trial results with a neoantigen vaccine may suggest the beginning of a paradigm shift in our view of the impact of immunosenescence on vaccination against novel infectious diseases.
Packaging signal of influenza A virus
Authors: Li Xiuli , Gu Min , Zheng Qinmei , Gao Ruyi , Liu Xiufan
Published: February 2021

Influenza A virus (IAV) contains a genome with eight single-stranded, negative-sense RNA segments that encode 17 proteins. During its assembly, all eight separate viral RNA (vRNA) segments are incorporated into virions in a selective manner. Evidence suggested that the highly selective genome packaging mechanism relies on RNA-RNA or protein-RNA interactions. The specific structures of each vRNA that contribute to mediating the packaging of the vRNA into virions have been described and identified as packaging signals. Abundant research indicated that sequences required for genome incorporation are not series and are varied among virus genotypes. The packaging signals play important roles in determining the virus replication, genome incorporation and genetic reassortment of influenza A virus. In this review, we discuss recent studies on influenza A virus packaging signals to provide an overview of their characteristics and functions.
Correction to: Poor sensitivity of "AccuPower SARS‑CoV‑2 real time RT‑PCR kit (Bioneer, South Korea)"
Authors: Freire‑Paspuel Byron , Garcia‑Bereguiain Miguel Angel
Published: February 2021

An amendment to this paper has been published and can be accessed via the original article.
Trust, risk, and the challenge of information sharing during a health emergency
Authors: Lencucha Raphael , Bandara Shashika
Published: February 2021

Information sharing is a critical element of an effective response to infectious disease outbreaks. The international system of coordination established through the World Health Organization via the International Health Regulations largely relies on governments to communicate timely and accurate information about health risk during an outbreak. This information supports WHO’s decision making process for declaring a public health emergency of international concern. It also aides the WHO to work with governments to coordinate efforts to contain cross-border outbreaks.

Given the importance of information sharing by governments, it is not surprising that governments that withhold or delay sharing information about outbreaks within their borders are often condemned by the international community for non-compliance with the International Health Regulations. The barriers to rapid and transparent information sharing are numerous. While governments must be held accountable for delaying or withholding information, in many cases non-compliance may be a rational response to real and perceived risks rather than a problem of technical incapacity or a lack of political commitment. Improving adherence to the International Health Regulations will require a long-term process to build trust that incorporates recognizing and mitigating the potential and perceived risks of information sharing.