bluuebunny/crossref_metadata_2025 huggingface dataset:
Integrating peptides' sequence and energy of contact residues information improves prediction of peptide and HLA-I binding with unknown alleles
Authors: Luo Fei , Gao Yangyang , Zhu Yongqiong , Liu Juan
Published: December 2019

Background

The HLA (human leukocyte antigen) class I is a kind of molecule encoded by a large family of genes and is characteristic of high polymorphism. Now the number of the registered HLA-I molecules has exceeded 3000. Slight differences in the amino acid sequences of HLAs would make them bind to different sets of peptides. In the past decades, although many methods have been proposed to predict the binding between peptides and HLA-I molecules and achieved good performance, most experimental data used by them is limited to the HLAs with a small number of alleles. Thus they are inclined to obtain high prediction accuracy only for data with similar alleles. Because the peptides and HLAs together determine the binding, it's necessary to consider their contribution meanwhile.

Results

By taking into account the features of the peptides sequence and the energy of contact residues, in this paper a method based on the artificial neural network is proposed to predict the binding of peptides and HLA-I even when the HLAs' potential alleles are unknown. Two experiments in the allele-specific and super-type cases are performed respectively to validate our method. In the first case, we collect 14 HLA-A and 14 HLA-B molecules on Bjoern Peters dataset, and compare our method with the ARB, SMM, NetMHC and other 16 online methods. Our method gets the best average AUC (Area under the ROC) value as 0.909. In the second one, we use leave one out cross validation on MHC-peptide binding data that has different alleles but shares the common super-type. Compared to gold standard methods like NetMHC and NetMHCpan, our method again achieves the best average AUC value as 0.847.

Conclusions

Our method achieves satisfactory results. Whenever it's tested on the HLA-I with single definite gene or with super-type gene locus, it gets better classification accuracy. Especially, when the training set is small, our method still works better than the other methods in the comparison. Therefore, we could make a conclusion that by combining the peptides' information, HLAs amino acid residues' interaction information and contact energy, our method really could improve prediction of the peptide HLA-I binding even when there aren't the prior experimental dataset for HLAs with various alleles.
Comprehensive analysis of microRNAs in breast cancer
Authors: Chang Hong-Tai , Li Sung-Chou , Ho Meng-Ru , Pan Hung-Wei , Ger Luo-Ping , Hu Ling-Yueh , Yu Shou-Yu , Li Wen-Hsiung , Tsai Kuo-Wang
Published: December 2019

Background

MicroRNAs (miRNAs) are short noncoding RNAs (approximately 22 nucleotides in length) that play important roles in breast cancer progression by downregulating gene expression. The detailed mechanisms and biological functions of miRNA molecules in breast carcinogenesis have yet to be fully elucidated. This study used bioinformatics and experimental approaches to conduct detailed analysis of the dysregulated miRNAs, arm selection preferences, 3' end modifications, and position shifts in isoforms of miRNAs (isomiRs) in breast cancer.

Methods

Next-generation sequencing (NGS) data on breast cancer was obtained from the NCBI Sequence Read Archive (SRA). The miRNA expression profiles and isomiRs in normal breast and breast tumor tissues were determined by mapping the clean reads back to human miRNAs. Differences in miRNA expression and pre-miRNA 5p/3p arm usage between normal and breast tumor tissues were further investigated using stem-loop reverse transcription and real-time polymerase chain reaction.

Results

The analysis identified and confirmed the aberrant expression of 22 miRNAs in breast cancer. Results from pathway enrichment analysis further indicated that the aberrantly expressed miRNAs play important roles in breast carcinogenesis by regulating the mitogen-activated protein kinase (MAPK) signaling pathway. Data also indicated that the position shifts in isomiRs and 3' end modifications were consistent in breast tumor and adjacent normal tissues, and that 5p/3p arm usage of some miRNAs displayed significant preferences in breast cancer.

Conclusions

Expression pattern and arm selection of miRNAs are significantly varied in breast cancers through analyzing NGS data and experimental approach. These miRNA candidates have high potential to play critical roles in the progression of breast cancer and could potentially provide as targets for future therapy.
Blocking Protein kinase C signaling pathway: mechanistic insights into the anti-leishmanial activity of prospective herbal drugs from Withania somnifera
Authors: Grover Abhinav , Katiyar Shashank Prakash , Jeyakanthan Jeyaraman , Dubey Vikash Kumar , Sundar Durai
Published: December 2019

Background

Leishmaniasis is caused by several species of leishmania protozoan and is one of the major vector-born diseases after malaria and sleeping sickness. Toxicity of available drugs and drug resistance development by protozoa in recent years has made Leishmaniasis cure difficult and challenging. This urges the need to discover new antileishmanial-drug targets and antileishmanial-drug development.

Results

Tertiary structure of leishmanial protein kinase C was predicted and found stable with a RMSD of 5.8Å during MD simulations. Natural compound withaferin A inhibited the predicted protein at its active site with -28.47 kcal/mol binding free energy. Withanone was also found to inhibit LPKC with good binding affinity of -22.57 kcal/mol. Both withaferin A and withanone were found stable within the binding pocket of predicted protein when MD simulations of ligand-bound protein complexes were carried out to examine the consistency of interactions between the two.

Conclusions

Leishmanial protein kinase C (LPKC) has been identified as a potential target to develop drugs against Leishmaniasis. We modelled and refined the tertiary structure of LPKC using computational methods such as homology modelling and molecular dynamics simulations. This structure of LPKC was used to reveal mode of inhibition of two previous experimentally reported natural compounds from Withania somnifera - withaferin A and withanone.
Literature aided determination of data quality and statistical significance threshold for gene expression studies
Authors: Xu Lijing , Cheng Cheng , George E Olusegun , Homayouni Ramin
Published: December 2019

Background

Gene expression data are noisy due to technical and biological variability. Consequently, analysis of gene expression data is complex. Different statistical methods produce distinct sets of genes. In addition, selection of expression p-value (EPv) threshold is somewhat arbitrary. In this study, we aimed to develop novel literature based approaches to integrate functional information in analysis of gene expression data.

Methods

Functional relationships between genes were derived by Latent Semantic Indexing (LSI) of Medline abstracts and used to calculate the function cohesion of gene sets. In this study, literature cohesion was applied in two ways. First, Literature-Based Functional Significance (LBFS) method was developed to calculate a p-value for the cohesion of differentially expressed genes (DEGs) in order to objectively evaluate the overall biological significance of the gene expression experiments. Second, Literature Aided Statistical Significance Threshold (LASST) was developed to determine the appropriate expression p-value threshold for a given experiment.

Results

We tested our methods on three different publicly available datasets. LBFS analysis demonstrated that only two experiments were significantly cohesive. For each experiment, we also compared the LBFS values of DEGs generated by four different statistical methods. We found that some statistical tests produced more functionally cohesive gene sets than others. However, no statistical test was consistently better for all experiments. This reemphasizes that a statistical test must be carefully selected for each expression study. Moreover, LASST analysis demonstrated that the expression p-value thresholds for some experiments were considerably lower (p < 0.02 and 0.01), suggesting that the arbitrary p-values and false discovery rate thresholds that are commonly used in expression studies may not be biologically sound.

Conclusions

We have developed robust and objective literature-based methods to evaluate the biological support for gene expression experiments and to determine the appropriate statistical significance threshold. These methods will assist investigators to more efficiently extract biologically meaningful insights from high throughput gene expression experiments.
A computational approach for identifying microRNA-target interactions using high-throughput CLIP and PAR-CLIP sequencing
Authors: Chou Chih-Hung , Lin Feng-Mao , Chou Min-Te , Hsu Sheng-Da , Chang Tzu-Hao , Weng Shun-Long , Shrestha Sirjana , Hsiao Chiung-Chih , Hung Jui-Hung , Huang Hsien-Da
Published: December 2019

Background

MicroRNAs (miRNAs) play a critical role in down-regulating gene expression. By coupling with Argonaute family proteins, miRNAs bind to target sites on mRNAs and employ translational repression. A large amount of miRNA-target interactions (MTIs) have been identified by the crosslinking and immunoprecipitation (CLIP) and the photoactivatable-ribonucleoside-enhanced CLIP (PAR-CLIP) along with the next-generation sequencing (NGS). PAR-CLIP shows high efficiency of RNA co-immunoprecipitation, but it also lead to T to C conversion in miRNA-RNA-protein crosslinking regions. This artificial error obviously reduces the mappability of reads. However, a specific tool to analyze CLIP and PAR-CLIP data that takes T to C conversion into account is still in need.

Results

We herein propose the first CLIP and PAR-CLIP sequencing analysis platform specifically for miRNA target analysis, namely miRTarCLIP. From scratch, it automatically removes adaptor sequences from raw reads, filters low quality reads, reverts C to T, aligns reads to 3'UTRs, scans for read clusters, identifies high confidence miRNA target sites, and provides annotations from external databases. With multi-threading techniques and our novel C to T reversion procedure, miRTarCLIP greatly reduces the running time comparing to conventional approaches. In addition, miRTarCLIP serves with a web-based interface to provide better user experiences in browsing and searching targets of interested miRNAs. To demonstrate the superior functionality of miRTarCLIP, we applied miRTarCLIP to two public available CLIP and PAR-CLIP sequencing datasets. miRTarCLIP not only shows comparable results to that of other existing tools in a much faster speed, but also reveals interesting features among these putative target sites. Specifically, we used miRTarCLIP to disclose that T to C conversion within position 1-7 and that within position 8-14 of miRNA target sites are significantly different (p value = 0.02), and even more significant when focusing on sites targeted by top 102 highly expressed miRNAs only (p value = 0.01). These results comply with previous findings and further suggest that combining miRNA expression and PAR-CLIP data can improve accuracy of the miRNA target prediction.

Conclusion

To sum up, we devised a systematic approach for mining miRNA-target sites from CLIP-seq and PAR-CLIP sequencing data, and integrated the workflow with a graphical web-based browser, which provides a user friendly interface and detailed annotations of MTIs. We also showed through real-life examples that miRTarCLIP is a powerful tool for understanding miRNAs. Our integrated tool can be accessed online freely at http://miRTarCLIP.mbc.nctu.edu.tw.
Characterization and genomic analysis of chromate resistant and reducing Bacillus cereus strain SJ1
Authors: He Minyan , Li Xiangyang , Guo Liang , Miller Susan J , Rensing Christopher , Wang Gejiao
Published: December 2019

Background

Chromium is a toxic heavy metal, which primarily exists in two inorganic forms, Cr(VI) and Cr(III). Chromate [Cr(VI)] is carcinogenic, mutational, and teratogenic due to its strong oxidizing nature. Biotransformation of Cr(VI) to less-toxic Cr(III) by chromate-resistant and reducing bacteria has offered an ecological and economical option for chromate detoxification and bioremediation. However, knowledge of the genetic determinants for chromate resistance and reduction has been limited so far. Our main aim was to investigate chromate resistance and reduction by Bacillus cereus SJ1, and to further study the underlying mechanisms at the molecular level using the obtained genome sequence.

Results

Bacillus cereus SJ1 isolated from chromium-contaminated wastewater of a metal electroplating factory displayed high Cr(VI) resistance with a minimal inhibitory concentration (MIC) of 30 mM when induced with Cr(VI). A complete bacterial reduction of 1 mM Cr(VI) was achieved within 57 h. By genome sequence analysis, a putative chromate transport operon, chrIA 1, and two additional chrA genes encoding putative chromate transporters that likely confer chromate resistance were identified. Furthermore, we also found an azoreductase gene azoR and four nitroreductase genes nitR possibly involved in chromate reduction. Using reverse transcription PCR (RT-PCR) technology, it was shown that expression of adjacent genes chrA 1 and chrI was induced in response to Cr(VI) but expression of the other two chromate transporter genes chrA 2 and chrA 3 was constitutive. In contrast, chromate reduction was constitutive in both phenotypic and gene expression analyses. The presence of a resolvase gene upstream of chrIA 1, an arsenic resistance operon and a gene encoding Tn7-like transposition proteins ABBCCCD downstream of chrIA 1 in B. cereus SJ1 implied the possibility of recent horizontal gene transfer.

Conclusion

Our results indicate that expression of the chromate transporter gene chrA 1 was inducible by Cr(VI) and most likely regulated by the putative transcriptional regulator ChrI. The bacterial Cr(VI)-resistant level was also inducible. The presence of an adjacent arsenic resistance gene cluster nearby the chrIA 1 suggested that strong selective pressure by chromium and arsenic could cause bacterial horizontal gene transfer. Such events may favor the survival and increase the resistance level of B. cereus SJ1.
Significance of Cuscutain, a cysteine protease from Cuscuta reflexa, in host-parasite interactions
Authors: Bleischwitz Marc , Albert Markus , Fuchsbauer Hans-Lothar , Kaldenhoff Ralf
Published: December 2019

Background

Plant infestation with parasitic weeds likeCuscuta reflexainduces morphological as well as biochemical changes in the host and the parasite. These modifications could be caused by a change in protein or gene activity. Using a comparative macroarray approachCuscutagenes specifically upregulated at the host attachment site were identified.

Results

One of the infestation specificCuscutagenes encodes a cysteine protease. The protein and its intrinsic inhibitory peptide were heterologously expressed, purified and biochemically characterized. The haustoria specific enzyme was named cuscutain in accordance with similar proteins from other plants, e.g. papaya. The role of cuscutain and its inhibitor during the host parasite interaction was studied by external application of an inhibitor suspension, which induced a significant reduction of successful infection events.

Conclusions

The study provides new information about molecular events during the parasitic plant - host interaction. Inhibition of cuscutain cysteine proteinase could provide means for antagonizing parasitic plants.
Molecular basis for defect in Alix-binding by alternatively spliced isoform of ALG-2 (ALG-2ΔGF122) and structural roles of F122 in target recognition
Authors: Inuzuka Tatsutoshi , Suzuki Hironori , Kawasaki Masato , Shibata Hideki , Wakatsuki Soichi , Maki Masatoshi
Published: December 2019

Background

ALG-2 (a gene product of PDCD6) belongs to the penta-EF-hand (PEF) protein family and Ca2+-dependently interacts with various intracellular proteins including mammalian Alix, an adaptor protein in the ESCRT system. Our previous X-ray crystal structural analyses revealed that binding of Ca2+ to EF3 enables the side chain of R125 to move enough to make a primary hydrophobic pocket (Pocket 1) accessible to a short fragment of Alix. The side chain of F122, facing a secondary hydrophobic pocket (Pocket 2), interacts with the Alix peptide. An alternatively spliced shorter isoform, designated ALG-2ΔGF122, lacks Gly121Phe122 and does not bind Alix, but the structural basis of the incompetence has remained to be elucidated.

Results

We solved the X-ray crystal structure of the PEF domain of ALG-2ΔGF122 in the Ca2+-bound form and compared it with that of ALG-2. Deletion of the two residues shortened α-helix 5 (α5) and changed the configuration of the R125 side chain so that it partially blocked Pocket 1. A wall created by the main chain of 121-GFG-123 and facing the two pockets was destroyed. Surprisingly, however, substitution of F122 with Ala or Gly, but not with Trp, increased the Alix-binding capacity in binding assays. The F122 substitutions exhibited different effects on binding of ALG-2 to other known interacting proteins, including TSG101 (Tumor susceptibility gene 101) and annexin A11. The X-ray crystal structure of the F122A mutant revealed that removal of the bulky F122 side chain not only created an additional open space in Pocket 2 but also abolished inter-helix interactions with W95 and V98 (present in α4) and that α5 inclined away from α4 to expand Pocket 2, suggesting acquirement of more appropriate positioning of the interacting residues to accept Alix.

Conclusions

We found that the inability of the two-residue shorter ALG-2 isoform to bind Alix is not due to the absence of bulky side chain of F122 but due to deformation of a main-chain wall facing pockets 1 and 2. Moreover, a residue at the position of F122 contributes to target specificity and a smaller side chain is preferable for Alix binding but not favored to bind annexin A11.
Improved method for protein complex detection using bottleneck proteins
Authors: Ahn Jaegyoon , Lee Dae Hyun , Yoon Youngmi , Yeu Yunku , Park Sanghyun
Published: December 2019

Background

Detecting protein complexes is one of essential and fundamental tasks in understanding various biological functions or processes. Therefore accurate identification of protein complexes is indispensable.

Methods

For more accurate detection of protein complexes, we propose an algorithm which detects dense protein sub-networks of which proteins share closely located bottleneck proteins. The proposed algorithm is capable of finding protein complexes which allow overlapping with each other.

Results

We applied our algorithm to several PPI (Protein-Protein Interaction) networks of Saccharomyces cerevisiae and Homo sapiens, and validated our results using public databases of protein complexes. The prediction accuracy was even more improved over our previous work which used also bottleneck information of the PPI network, but showed limitation when predicting small-sized protein complex detection.

Conclusions

Our algorithm resulted in overlapping protein complexes with significantly improved F1 score over existing algorithms. This result comes from high recall due to effective network search, as well as high precision due to proper use of bottleneck information during the network search.
HDAM: a resource of human disease associated mutations from next generation sequencing studies
Authors: Jia Meiwen , Liu Yanli , Shen Zhongchao , Zhao Chen , Zhang Meixia , Yi Zhenghui , Wen Chengping , Deng Youping , Shi Tieliu
Published: December 2019

Background

Next generation sequencing (NGS) technologies have greatly facilitated the rapid and economical detection of pathogenic mutations in human disorders. However, mutation descriptions are hard to be compared and integrated due to various reference sequences and annotation tools adopted in different articles as well as the nomenclature of diseases/traits.

Description

The Human Disease Associated Mutation (HDAM) database is dedicated to collect, standardize and re-annotate mutations for human diseases discovered by NGS studies. In the current release, HDAM contains 1,114 mutations, located in 669 genes and associated with 125 human diseases through literature mining. All mutation records have uniform and unequivocal descriptions of sequence changes according to the Human Genome Sequence Variation Society (HGVS) nomenclature recommendations. Each entry displays comprehensive information, including mutation location in genome (hg18/hg19), gene functional annotation, protein domain annotation, susceptible diseases, the first literature report of the mutation and etc. Moreover, new mutation-disease relationships predicted by Bayesian network are also presented under each mutation.

Conclusion

HDAM contains hundreds rigorously curated human mutations from NGS studies and was created to provide a comprehensive view of these mutations that confer susceptibility to the common disorders. HDAM can be freely accessed at http://www.megabionet.org/HDAM.
Exploring the pathogenetic association between schizophrenia and type 2 diabetes mellitus diseases based on pathway analysis
Authors: Liu Yanli , Li Zezhi , Zhang Meixia , Deng Youping , Yi Zhenghui , Shi Tieliu
Published: December 2019

Background

Schizophrenia (SCZ) and type 2 diabetes mellitus (T2D) are both complex diseases. Accumulated studies indicate that schizophrenia patients are prone to present the type 2 diabetes symptoms, but the potential mechanisms behind their association remain unknown. Here we explored the pathogenetic association between SCZ and T2D based on pathway analysis and protein-protein interaction.

Results

With sets of prioritized susceptibility genes for SCZ and T2D, we identified significant pathways (with adjusted p-value < 0.05) specific for SCZ or T2D and for both diseases based on pathway enrichment analysis. We also constructed a network to explore the crosstalk among those significant pathways. Our results revealed that some pathways are shared by both SCZ and T2D diseases through a number of susceptibility genes. With 382 unique susceptibility proteins for SCZ and T2D, we further built a protein-protein interaction network by extracting their nearest interacting neighbours. Among 2,104 retrieved proteins, 364 of them were found simultaneously interacted with susceptibility proteins of both SCZ and T2D, and proposed as new candidate risk factors for both diseases. Literature mining supported the potential association of partial new candidate proteins with both SCZ and T2D. Moreover, some proteins were hub proteins with high connectivity and interacted with multiple proteins involved in both diseases, implying their pleiotropic effects for the pathogenic association. Some of these hub proteins are the components of our identified enriched pathways, including calcium signaling, g-secretase mediated ErbB4 signaling, adipocytokine signaling, insulin signaling, AKT signaling and type II diabetes mellitus pathways. Through the integration of multiple lines of information, we proposed that those signaling pathways, which contain susceptibility genes for both diseases, could be the key pathways to bridge SCZ and T2D. AKT could be one of the important shared components and may play a pivotal role to link both of the pathogenetic processes.

Conclusions

Our study is the first network and pathway-based systematic analysis for SCZ and T2D, and provides the general pathway-based view of pathogenetic association between two diseases. Moreover, we identified a set of candidate genes potentially contributing to the linkage between these two diseases. This research offers new insights into the potential mechanisms underlying the co-occurrence of SCZ and T2D, and thus, could facilitate the inference of novel hypotheses for the co-morbidity of the two diseases. Some etiological factors that exert pleiotropic effects shared by the significant pathways of two diseases may have important implications for the diseases and could be therapeutic intervention targets.
Identification of multiple gene-gene interactions for ordinal phenotypes
Authors: Kim Kyunga , Kwon Min-Seok , Oh Sohee , Park Taesung
Published: December 2019

Background

Multifactor dimensionality reduction (MDR) is a powerful method for analysis of gene-gene interactions and has been successfully applied to many genetic studies of complex diseases. However, the main application of MDR has been limited to binary traits, while traits having ordinal features are commonly observed in many genetic studies (e.g., obesity classification - normal, pre-obese, mild obese and severe obese).

Methods

We propose ordinal MDR (OMDR) to facilitate gene-gene interaction analysis for ordinal traits. As an alternative to balanced accuracy, the use of tau-b, a common ordinal association measure, was suggested to evaluate interactions. Also, we generalized cross-validation consistency (GCVC) to identify multiple best interactions. GCVC can be practically useful for analyzing complex traits, especially in large-scale genetic studies.

Results and conclusions

In simulations, OMDR showed fairly good performance in terms of power, predictability and selection stability and outperformed MDR. For demonstration, we used a real data of body mass index (BMI) and scanned 1~4-way interactions of obesity ordinal and binary traits of BMI via OMDR and MDR, respectively. In real data analysis, more interactions were identified for ordinal trait than binary traits. On average, the commonly identified interactions showed higher predictability for ordinal trait than binary traits. The proposed OMDR and GCVC were implemented in a C/C++ program, executables of which are freely available for Linux, Windows and MacOS upon request for non-commercial research institutions.
Prevalence of diabetes mellitus and impaired glucose tolerance in a rural community of Angola
Authors: Evaristo-Neto Antonio D , Foss-Freitas Maria Cristina , Foss Milton C
Published: December 2019

Background

To determine the prevalence of diabetes mellitus (DM) and impaired glucose tolerance (IGT) in a rural community (Bengo) of Angola.

Methods

A random sample of 421 subjects aged 30 to 69 years (30% men and 70% women) was selected from three villages of Bengo province. This cross-sectional home survey was conducted using a sampling design of stage conglomerates. First, clinical and anthropometric data were obtained and fasting capillary glucose level was determined. Subjects who screened positive (fasting capillary glucose ≥ 100 mg/dl and < 200 mg/dl) and each sixth consecutive subject who screened negative (fasting capillary glucose < 100 mg/dl) were submitted to the second phase of survey, consisting of the 75-g oral glucose tolerance test. Data was analyzed by the use of SAS statistical software.

Results

The prevalence rates of diabetes mellitus and IGT were 2.8% and 8.1%, respectively. The age group with the highest prevalence of diabetes was 60 to 69 years (42%). Impaired glucose tolerance prevalence was 38% in the 40 to 49 year age group and it increased with age, considering that the 50 to 59 and 60 to 69 year age groups as a whole represent 50% of all subjects with impaired glucose tolerance. The prevalence of diabetes mellitus did not differ significantly between men (3.2%) and women (2.7%) (p = 0.47). On the other hand, the prevalence of impaired glucose tolerance among women showed almost twice that found in men (9.1% vs. 5.6%, respectively). Overweight was present in 66.7% of the individuals with diabetes mellitus and 26.5% of individuals with impaired glucose tolerance showed overweight or obesity.

Conclusions

Although the prevalence of diabetes mellitus was low, the prevalence of impaired glucose tolerance is considered to be within an intermediary range, suggesting a future increase in the frequency of diabetes in this population.
LPS immune challenge reduces arcuate nucleus TSHR and CART mRNA and elevates plasma CART peptides
Authors: Burgos Jonathan R. , Iresjö Britt-Marie , Olsson Linda , Smedh Ulrika
Published: December 2019

Background

The aim was to examine the impact of lipopolysaccharide-induced systemic inflammation on expression of mRNA for cocaine- and amphetamine-regulated transcript (CART) and the thyrotropin receptor (TSHR) and its ligands in CNS areas of relevance for feeding controls and metabolism. Lipopolysaccharide effects on plasma levels of TSH and CART peptides were also examined.

Methods

Lipopolysaccharide (150–200 μg/mouse) was injected in C57BL/6J mice and tissue and plasma samples taken after 24 h. To establish if plasma increase in CART peptide levels were prostanoid dependent, indomethacin was given via the drinking water beginning 48 h prior to LPS. We evaluated mRNA expression for CART, TSHR, TSHβ, and thyrostimulin in brain and pituitary extracts. Plasma levels of TSH, CARTp, and serum amyloid P component were analyzed by ELISA.

Results

Lipopolysaccharide suppressed TSHR mRNA expression in the arcuate nucleus and the pituitary. CART mRNA expression was reduced in the arcuate nucleus but elevated in the pituitary of mice treated with Lipopolysaccharide, whereas plasma TSH remained unchanged. Plasma CART peptide concentration increased after LPS treatment in a prostanoid-independent manner, and CART peptide levels correlated positively to degree of inflammation.

Conclusions

Our findings suggest that central and peripheral CART is affected by acute inflammation. Considering the role of the arcuate nucleus in feeding controls, our data highlight TSHR and CART as putative neuroendocrine signaling components that respond to inflammation, perhaps to maintain weight and metabolic homeostasis during states of disease.
Strategies for recruitment in general practice settings: the iSOLVE fall prevention pragmatic cluster randomised controlled trial
Authors: Tan Amy C. W. , Clemson Lindy , Mackenzie Lynette , Sherrington Catherine , Roberts Chris , Tiedemann Anne , Pond Constance D. , White Fiona , Simpson Judy M.
Published: December 2019

Background

Falls are common among older people, and General Practitioners (GPs) could play an important role in implementing strategies to manage fall risk. Despite this, fall prevention is not a routine activity in general practice settings. The iSOLVE cluster randomised controlled trial aimed to evaluate implementation of a fall prevention decision tool in general practice. This paper sought to describe the strategies used and reflect on the enablers and barriers relevant to successful recruitment of general practices, GPs and their patients.

Methods

Recruitment was conducted within the geographical area of a Primary Health Network in Northern Sydney, Australia. General practices and GPs were engaged via online surveys, mailed invitations to participate, educational workshops, practitioner networks and promotional practice visits. Patients 65 years or older were recruited via mailed invitations, incorporating the practice letterhead and the name(s) of participating GP(s). Observations of recruitment strategies, results and enabling factors were recorded in field notes as descriptive and narrative data, and analysed using mixed-methods.

Results

It took 19 months to complete recruitment of 27 general practices, 75 GPs and 560 patients. The multiple strategies used to engage general practices and GPs were collectively useful in reaching the targeted sample size. Practice visits were valuable in engaging GPs and staff, establishing interest in fall prevention and commitment to the trial. A mix of small, medium and large practices were recruited. While some were recruited as a whole-practice, other practices had few or half of the number of GPs recruited. The importance of preventing falls in older patients, simplicity of research design, provision of resources and logistic facilitation of patient recruitment appealed to GPs. Recruitment of older patients was successfully achieved by mailed invitations which was a strategy that was familiar to practice staff and patients. Patient response rates were above the expected 10% for most practices. Many practices (n = 17) achieved the targeted number of 20 or more patients.

Conclusions

Recruitment in general practice settings can be successfully achieved through multiple recruitment strategies, effective communication and rapport building, ensuring research topic and design suit general practice needs, and using familiar communication strategies to engage patients.

Trial registration

The trial was prospectively registered on 29 April 2015 with the Australian New Zealand Clinical Trial Registry www.anzctr.org.au (trial ID: ACTRN12615000401550).
Process evaluation of the community-based newborn care program implementation in Geze Gofa district, south Ethiopia: a case study evaluation design
Authors: Gebremedhin Tsegaye , Daka Dawit Wolde , Alemayehu Yibeltal Kiflie , Yitbarek Kiddus , Debie Ayal
Published: December 2019

Background

The Community-Based Newborn Care (CBNC) program is a comprehensive strategy designed to improve the health of newborns during pregnancy, childbirth, and the postnatal period through health extension workers at community levels, although the implementation has not been evaluated yet. Therefore, this study aimed to evaluate the process of the CBNC program implementation in Geze Gofa district, south Ethiopia.

Methods

A case study evaluation design with a mixed method was employed from May 1 to 31, 2017. A total of 321 mothers who gave birth from September 01, 2016 to February 29, 2017, were interviewed. Similarly, 27 direct observations, six-month document reviews, and 14 key informant interviews were conducted. The quantitative data were entered into Epi-Data version 3.1 and exported to SPSS version 20 for analysis. In the multivariable logistic regression analysis, variables with < 0.05 p-values and Adjusted Odds Ratio (AOR) with 95% Confidence Interval (CI) were used to declare factors associated with maternal satisfaction. The qualitative data were transcribed, translated, coded, and analyzed using thematic analysis. The overall process of program implementation was measured based on pre-determined judgmental criteria.

Results

The overall level of the implementation process of the CBNC program was 72.7%, to which maternal satisfaction, availability of resources, and healthcare providers’ compliance with the national guideline contributed 75.0, 81.0, and 68.0%, respectively. Essential drugs and medical equipment, like vitamin K, chlorohexidine ointment, neonatal resuscitation bags, and masks used in the program were out of stock. Very severe diseases were not treated according to the national guidelines, and the identification of neonatal sepsis cases was poor. Trading occupation (AOR: 0.16, 95% CI: 0.03–0.97) and low wealth status (AOR: 3.11, 95% CI: 1.16–8.36) were factors associated with maternal satisfaction.

Conclusion

The process of CBNC program implementation was relatively good, although the compliance of healthcare providers with the national guideline and maternal satisfaction with the services was low. Some essential drugs and medical equipment were out of stock. Merchant and low wealth status affected maternal satisfaction. Therefore, healthcare offices should provide crucial medicines and equipment for better program implementation and improve the wealth status of mothers to enhance maternal satisfaction.
Assessment of precision irradiation in early non-small cell lung cancer and interstitial lung disease (ASPIRE-ILD): study protocol for a phase II trial
Authors: Palma David A. , Chen Hanbo , Bahig Houda , Gaede Stewart , Harrow Stephen , Laba Joanna M. , Qu X. Melody , Rodrigues George B. , Yaremko Brian P. , Yu Edward , Louie Alexander V. , Dhaliwal Inderdeep , Ryerson Christopher J.
Published: December 2019

Background

Stereotactic ablative radiotherapy (SABR) has become an established treatment option for medically-inoperable early-stage (Stage I-IIA) non-small cell lung cancer (ES-NSCLC). SABR is able to obtain high rates of local control with low rates of symptomatic toxicity in this patient population. However, in a subset of patients with fibrotic interstitial lung disease (ILD), elevated rates of SABR-related toxicity and mortality have been described. The Assessment of Precision Irradiation in Early Non-Small Cell Lung Cancer and Interstitial Lung Disease (ASPIRE-ILD) study will conduct a thorough prospective evaluation of the clinical outcomes, toxicity, changes in diagnostic test parameters and patient-related outcomes following SABR for ES-NSCLC for patients with fibrotic ILD.

Methods

ASPIRE-ILD is a single-arm Phase II prospective study. The accrual target is 39 adult patients with T1–2N0M0 non-small cell lung cancer with co-existing ILD who are not candidates for surgical excision. Pathological confirmation of diagnosis is strongly recommended but not strictly required. Enrolled patients will be stratified by ILD-related mortality risk. The starting SABR dose will be 50 Gy in 5 fractions every other day (biologically effective dose: 100 Gy10 or 217 Gy3), but the radiation dose can be de-escalated up to two times to 50 Gy in 10 fractions daily (75 Gy10 or 133 Gy3) and 45 Gy in 15 fractions daily (58 Gy10 or 90 Gy3). Dose de-escalation will occur if 2 or more of the first 7 patients in a cohort experiences grade 5 toxicity within 6 months of treatment. Similarly, dose de-escalation can also occur if 2 or more of the first 7 patients with a specific subtype of ILD experiences grade 5 toxicity within 6 months of treatment. The primary endpoint is overall survival. Secondary endpoints include toxicity (CTC-AE 4.0), progression-free survival, local control, patient-reported outcomes (cough severity and quality of life), rates of ILD exacerbation and changes in pulmonary function tests/high-resolution computed tomography findings post-SABR.

Discussion

ASPIRE-ILD will be the first prospective study specifically designed to comprehensively evaluate the effectiveness and safety of SABR for ES-NSCLC in patients with co-existing ILD.

Trial registration

Clinicaltrials.gov identifier: NCT03485378. Date of registration: April 2, 2018.
Who is afraid of ticks and tick-borne diseases? Results from a cross-sectional survey in Scandinavia
Authors: Slunge Daniel , Jore Solveig , Krogfelt Karen Angeliki , Jepsen Martin Tugwell , Boman Anders
Published: December 2019

Background

In Scandinavia, the distribution of ticks is expanding and tick-borne diseases constitute growing health risks. While the probability of getting a tick-borne disease after a tick bite is low, the health impacts can be large. This, as well as other characteristics of these diseases make tick-related risks difficult for laypeople to assess and perceived risk may differ substantially from actual risk. Understanding risk perceptions is important since it is the perceived risk, rather than actual risk, that determine behaviour and even more so for new and emerging risks. The aim of this study is to investigate knowledge and risk perceptions related to tick bites and the tick-borne diseases Lyme borreliosis (LB) and tick-borne encephalitis (TBE). By analysing risk perceptions and knowledge, the study helps inform the development of public health strategies in response to the increasing incidence of these diseases in Scandinavia.

Methods

Two thousand, six hundred sixty-eight respondents in Denmark, Norway and Sweden answered an online questionnaire with 48 questions, including 7 questions on risk perceptions and 9 knowledge questions. Chi-squared tests were used to analyse statistical differences between country sub-samples, gender and age groups. A multivariate regression model was used to analyse factors associated with risk perceptions.

Results

Risk perceptions were on average high in comparison with scientific estimates, with respondents grossly overrating the probability of contracting LB or TBE if bitten by a tick. Also, the average perceived seriousness of a single tick bite and of getting LB or TBE was high. Knowledge on the other hand was low, especially among men and the youngest age group (18–29 years). Higher levels of knowledge about tick-borne diseases were associated with lower perceived seriousness of tick bites and LB and higher perceived seriousness of TBE. Also, having been diagnosed with LB was negatively associated with the perceived seriousness of LB.

Conclusions

Our results indicate that informing about ticks and tick-borne diseases would be a relevant public health strategy as it could make risk perceptions better aligned with actual risk.

Should the TBE virus spread further in Denmark and Norway, increasing knowledge about TBE vaccination would be especially important.
Under-reporting of TB cases and associated factors: a case study in China
Authors: Zhou Danju , Pender Michelle , Jiang Weixi , Mao Wenhui , Tang Shenglan
Published: December 2019

Background

Tuberculosis is a leading cause of death worldwide and has become a high global health priority. Accurate country level surveillance is critical to ending the pandemic. Effective routine reporting systems which track the course of the epidemic are vital in addressing TB. China, which has the third largest TB epidemic in the world and has developed a reporting system to help with the control and prevention of TB, this study examined its effectiveness in Eastern China.

Methods

The number of TB cases reported internally in two hospitals in Eastern China were compared to the number TB cases reported by these same hospitals in the national reporting systems in order to assess the accuracy of reporting. Qualitative data from interviews with key health officials and researcher experience using the TB reporting systems were used to identify factors affecting the accuracy of TB cases being reported in the national systems.

Results

This study found that over a quarter of TB cases recorded in the internal hospital records were not entered into the national TB reporting systems, leading to an under representation of national TB cases. Factors associated with underreporting included unqualified and overworked health personnel, poor supervision and accountability at local and national levels, and a complicated incohesive health information management system.

Conclusions

This study demonstrates that TB in Eastern China is being underreported. Given that Eastern China is a developed province, one could assume similar problems may be found in other parts of China with fewer resources as well as many low- and middle-income countries. Having an accurate account of the number of national TB cases is essential to understanding the national and global burden of the disease and in managing TB prevention and control efforts. As such, factors associated with underreporting need to be addressed in order to reduce underreporting.
Identifying risk factors of anemia among women of reproductive age in Rwanda – a cross-sectional study using secondary data from the Rwanda demographic and health survey 2014/2015
Authors: Hakizimana Dieudonne , Nisingizwe Marie Paul , Logan Jenae , Wong Rex
Published: December 2019

Background

Anemia among Women of Reproductive Age (WRA) continues to be among the major public health problems in many developing countries, including Rwanda, where it increased in prevalence between the 2015 and 2010 Rwanda Demographic and Health Survey (RDHS) reports. A thorough understanding of its risk factors is necessary to design better interventions. However, to the best of our knowledge, no study has been conducted in Rwanda on a nationally representative sample to assess factors associated with anemia among WRA. Accordingly, this study was conducted to address such gap.

Methods

A quantitative, cross-sectional study was conducted using data from the RDHS 2014–2015. The study population consisted of 6680 WRA who were tested for anemia during the survey. Anemia was defined as having a hemoglobin level equal to or below 10.9 g/dl for a pregnant woman, and hemoglobin level equal to or below 11.9 g/dl for a non-pregnant woman. Pearson’s chi-squared test and multiple logistic regression were conducted for bivariate and multivariable analysis, respectively.

Results

The prevalence of anemia among WRA was 19.2% (95% CI: 18.0–20.5). Four factors were found to be associated with lower odds of anemia, including being obese (OR: 0.61, 95% CI: 0.40–0.91), being in the rich category (OR: 0.74, 95% CI: 0.63–0.87), sleeping under a mosquito net (OR: 0.85, 95% CI: 0.74–0.98), and using hormonal contraceptives (OR: 0.61, 95% CI: 0.50–0.73). Five factors were associated with higher odds of anemia, including being underweight (OR: 1.39, 95% CI: 1.09–1.78), using an intrauterine device (OR: 1.98, 95% CI: 1.05–3.75), being separated or widowed (OR: 1.35, 95% CI: 1.09–1.67), and living in the Southern province (OR: 1.45, 95% CI: 1.11–1.89) or in the Eastern province (OR: 1.41, 95% CI: 1.06–1.88).

Conclusion

Anemia continues to pose public health challenges; novel public health interventions should consider geographic variations in anemia risk, seek to improve women’s economic statuses, and strengthen iron supplementation especially for Intrauterine device users. Additionally, given the association between anemia and malaria, interventions to prevent malaria should be enhanced.
Take -home naloxone rescue kits following heroin overdose in the emergency department to prevent opioid overdose related repeat emergency department visits, hospitalization and death- a pilot study
Authors: Papp Joan , Vallabhaneni Mayur , Morales Ariel , Schrock Jon W.
Published: December 2019

Background

Opioid overdoses are at an epidemic in the United States causing the deaths of thousands each year. Project DAWN (Deaths Avoided with Naloxone) is an opioid overdose education and naloxone distribution program in Ohio that distributes naloxone rescue kits at clinics and in the emergency departments of a single hospital system.

Methods

We performed a retrospective analytic cohort study comparing heroin overdose survivors who presented to the emergency department and were subsequently discharged. We compared those who received a naloxone rescue kit at discharge with those who did not. Our composite outcome was repeat opioid overdose related emergency department visit(s), hospitalization and death at 0–3 months and at 3–6 months following emergency department overdose. Heroin overdose encounters were identified by ICD- 9 or 10 codes and data was abstracted from the electronic medical record for emergency department patients who presented for heroin overdose and were discharged over a 31- month period between 2013 and 2016. Patients were excluded for previous naloxone access, incarceration, suicidal ideation, admission to the hospital or death from acute overdose on initial emergency department presentation. Data was analyzed with the Chi- square statistical test.

Results

We identified 291emergency department heroin overdose encounters by ICD-9 or 10 codes and were analyzed. A total of 71% of heroin overdose survivors received a naloxone rescue kit at emergency department discharge. Between the patients who did not receive a naloxone rescue kit at discharge, no overdose deaths occurred and 10.8% reached the composite outcome. Of the patients who received a naloxone rescue kit, 14.4% reached the composite endpoint and 7 opioid overdose deaths occurred in this cohort. No difference in mortality at 3 or 6 months was detected,p = 0.15 and 0.36 respectively. No difference in the composite outcome was detected at 3 or 6 months either,p = 0.9 and 0.99 respectively.

Conclusions

Of our emergency department patients receiving a naloxone rescue kit we did not find a benefit in the reduction of repeat emergency department visits hospitalizations, or deaths following a non-fatal heroin overdose.