bluuebunny/crossref_metadata_2025 huggingface dataset:
FitSearch: a robust way to interpret a yeast fitness profile in terms of drug's mode-of-action
Authors: Lee Minho , Han Sangjo , Chang Hyeshik , Kwak Youn-Sig , Weller David M , Kim Dongsup
Published: December 2019

Background

Yeast deletion-mutant collections have been successfully used to infer the mode-of-action of drugs especially by profiling chemical-genetic and genetic-genetic interactions on a genome-wide scale. Although tens of thousands of those profiles are publicly available, a lack of an accurate method for mining such data has been a major bottleneck for more widespread use of these useful resources.

Results

For general usage of those public resources, we designed FitRankDB as a general repository of fitness profiles, and developed a new search algorithm, FitSearch, for identifying the profiles that have a high similarity score with statistical significance for a given fitness profile. We demonstrated that our new repository and algorithm are highly beneficial to researchers who attempting to make hypotheses based on unknown modes-of-action of bioactive compounds, regardless of the types of experiments that have been performed using yeast deletion-mutant collection in various types of different measurement platforms, especially non-chip-based platforms.

Conclusions

We showed that our new database and algorithm are useful when attempting to construct a hypothesis regarding the unknown function of a bioactive compound through small-scale experiments with a yeast deletion collection in a platform independent manner. The FitRankDB and FitSearch enhance the ease of searching public yeast fitness profiles and obtaining insights into unknown mechanisms of action of drugs. FitSearch is freely available at http://fitsearch.kaist.ac.kr.
Passive administration of purified secretory IgA from human colostrum induces protection against Mycobacterium tuberculosis in a murine model of progressive pulmonary infection
Authors: Alvarez Nadine , Otero Oscar , Camacho Frank , Borrero Reinier , Tirado Yanely , Puig Alina , Aguilar Alicia , Rivas Cesar , Cervantes Axel , Falero-Díaz Gustavo , Cádiz Armando , Sarmiento María E , Norazmi Mohd Nor , Hernández-Pando Rogelio , Acosta Armando
Published: December 2019

Background

Immunoglobulin A is the most abundant isotype in secretions from mucosal surfaces of the gastrointestinal, respiratory and genitourinary tracts and in external secretions such as colostrum, breast milk, tears and saliva. The high concentration of human secretory IgA (hsIgA) in human colostrum strongly suggests that it should play an important role in the passive immune protection against gastrointestinal and respiratory infections.

Materials and methods

Human secretory IgA was purified from colostrum. The reactivity of hsIgA against mycobacterial antigens and its protective capacity against mycobacterial infection was evaluated.

Results

The passive administration of hsIgA reduces the pneumonic area before challenge withM.tuberculosis. The intratracheal administration ofM. tuberculosispreincubated with hsIgA to mice greatly reduced the bacterial load in the lungs and diminished lung tissue injury.

Conclusions

HsIgA purified from colostrum protects againstM. tuberculosisinfection in an experimental mouse model.
Presence of genes for type III secretion system 2 in Vibrio mimicus strains
Authors: Okada Natsumi , Matsuda Shigeaki , Matsuyama Junko , Park Kwon-Sam , de los Reyes Calvin , Kogure Kazuhiro , Honda Takeshi , Iida Tetsuya
Published: December 2019

Background

Vibrios, which include more than 100 species, are ubiquitous in marine and estuarine environments, and several of them e.g. Vibrio cholerae, V. parahaemolyticus, V. vulnificus and V. mimicus, are pathogens for humans. Pathogenic V. parahaemolyticus strains possess two sets of genes for type III secretion system (T3SS), T3SS1 and T3SS2. The latter are critical for virulence of the organism and be classified into two distinct phylogroups, T3SS2α and T3SS2β, which are reportedly also found in pathogenic V. cholerae non-O1/non-O139 serogroup strains. However, whether T3SS2-related genes are present in other Vibrio species remains unclear.

Results

We therefore examined the distribution of the genes for T3SS2 in vibrios other than V. parahaemolyticus by using a PCR assay targeting both T3SS2α and T3SS2β genes. Among the 32 Vibrio species tested in our study, several T3SS2-related genes were detected in three species, V. cholerae, V. mimicus and V. hollisae, and most of the essential genes for type III secretion were present in T3SS2-positive V. cholerae and V. mimicus strains. Moreover, both V. mimicus strains possessing T3SS2α and T3SS2β were identified. The gene organization of the T3SS2 gene clusters in V. mimicus strains was fundamentally similar to that of V. parahaemolyticus and V. cholerae in both T3SS2α- and T3SS2β-possessing strains.

Conclusions

This study is the first reported evidence of the presence of T3SS2 gene clusters in V. mimicus strains. This finding thus provides a new insight into the pathogenicity of the V. mimicus species.
A homeobox protein Phx1 regulates long-term survival and meiotic sporulation in Schizosaccharomyces pombe
Authors: Kim Ji-Yoon , Kwon Eun-Soo , Roe Jung-Hye
Published: December 2019

Background

In the fission yeast Schizosaccharomyces pombe, the phx1
+ (pombe homeobox) gene was initially isolated as a multi-copy suppressor of lysine auxotrophy caused by depletion of copper/zinc-containing superoxide dismutase (CuZn-SOD). Overproduction of Phx1 increased the synthesis of homocitrate synthase, the first enzyme in lysine biosynthetic pathway, which is labile to oxidative stress. Phx1 has a well conserved DNA-binding domain called homeodomain at the N-terminal region and is predicted to be a transcription factor in S. pombe. However, its role has not been revealed in further detail. Here we examined its expression pattern and the phenotype of its null mutant to get clues on its function.

Results

Fluorescence from the Phx1-GFP expressed from a chromosomal fusion gene demonstrated that it is localized primarily in the nucleus, and is distinctly visible during the stationary phase. When we replaced the N-terminal homeobox domain of Phx1 with the DNA binding domain of Pap1, a well-characterized transcription factor, the chimeric protein caused the elevation of transcripts from Pap1-dependent genes such as ctt1

+
and trr1

+
, suggesting that Phx1 possesses transcriptional activating activity when bound to DNA. The amount of phx1

+
transcripts sharply increased as cells entered the stationary phase and was maintained at high level throughout the stationary phase. Nutrient shift down to low nitrogen or carbon sources caused phx1

+
induction during the exponential phase, suggesting that cells need Phx1 for maintenance function during nutrient starvation. The Δphx1 null mutant showed decreased viability in long-term culture, whereas overproduction of Phx1 increased viability. Decrease in long-term survival was also observed for Δphx1 under N- or C-starved conditions. In addition, Δphx1 mutant was more sensitive to various oxidants and heat shock. When we examined sporulation of the Δphx1/Δphx1 diploid strain, significant decrease in the formation of meiotic spores was observed.

Conclusions

Phx1 is a transcriptional regulator whose synthesis is elevated during stationary phase and by nutrient starvation in S. pombe. It supports long-term survival and stress tolerance against oxidation and heat, and plays a key role in the formation of meiotic spores.
A method of active case detection to target reservoirs of asymptomatic malaria and gametocyte carriers in a rural area in Southern Province, Zambia
Authors: Stresman Gillian H , Kamanga Aniset , Moono Petros , Hamapumbu Harry , Mharakurwa Sungano , Kobayashi Tamaki , Moss William J , Shiff Clive
Published: December 2019

Background

Asymptomatic reservoirs of malaria parasites are common yet are difficult to detect, posing a problem for malaria control. If control programmes focus on mosquito control and treatment of symptomatic individuals only, malaria can quickly resurge if interventions are scaled back. Foci of parasite populations must be identified and treated. Therefore, an active case detection system that facilitates detection of asymptomatic parasitaemia and gametocyte carriers was developed and tested in the Macha region in southern Zambia.

Methods

Each week, nurses at participating rural health centres (RHC) communicated the number of rapid diagnostic test (RDT) positive malaria cases to a central research team. During the dry season when malaria transmission was lowest, the research team followed up each positive case reported by the RHC by a visit to the homestead. The coordinates of the location were obtained by GPS and all consenting residents completed a questionnaire and were screened for malaria using thick blood film, RDT, nested-PCR, and RT-PCR for asexual and sexual stage parasites. Persons who tested positive by RDT were treated with artemether/lumefantrine (Coartem®). Data were compared with a community-based study of randomly selected households to assess the prevalence of asymptomatic parasitaemia in the same localities in September 2009.

Results

In total, 186 and 141 participants residing in 23 case and 24 control homesteads, respectively, were screened. In the case homesteads for which a control population was available (10 of the 23), household members of clinically diagnosed cases had a 8.0% prevalence of malaria using PCR compared to 0.7% PCR positive individuals in the control group (p = 0.006). The case and control groups had a gametocyte prevalence of 2.3% and 0%, respectively but the difference was not significant (p = 0.145).

Conclusions

This pilot project showed that active case detection is feasible and can identify reservoirs of asymptomatic infection. A larger sample size, data over multiple low transmission seasons, and in areas with different transmission dynamics are needed to further validate this approach.
The cross-sectional associations between sense of coherence and diabetic microvascular complications, glycaemic control, and patients' conceptions of type 1 diabetes
Authors: Ahola Aila J , Saraheimo Markku , Forsblom Carol , Hietala Kustaa , Groop Per-Henrik ,   the FinnDiane Study Group
Published: December 2019

Background

Sense of coherence (SOC) has been associated with various self-care behaviours in the general population. As the management of type 1 diabetes heavily relies on self-management, the SOC concept could also prove important in this population. This paper is a report of a study conducted among patients with type 1 diabetes to assess the associations between SOC and glycaemic control, microvascular complications, and patients' conceptions of their disease.

Methods

Altogether 1,264 adult patients (45% men, age range 18-82 years) with type 1 diabetes participated in this cross-sectional study. SOC was evaluated using a 13-item SOC questionnaire. Standardized assays were used to determine HbA1c. Nephropathy status was based on albumin excretion rate and retinal laser-treatment was used as an indication of severe retinopathy. Patients' subjective conceptions of diabetes were studied using a questionnaire.

Results

Higher SOC scores, reflecting stronger SOC, were associated with lower HbA1c values. Strong SOC was independently associated with reaching the HbA1c level <7.5%. Adjusting for diabetes duration, age at onset, socioeconomic status and HbA1c, weak SOC was associated with the presence of nephropathy among men, but not women. No associations were observed between SOC and severe retinopathy. Four dimensions describing patients' conceptions of HbA1c, complications, diabetes control and hypoglycaemia were formed from the diabetes questionnaire. Weak SOC was independently associated with worse subjective conceptions in the dimensions of HbA1c and hypoglycaemia. Furthermore among men, an association between weak SOC and the complications factor was observed.

Conclusion

Interventions to improve patients' SOC, if available, could improve patients' metabolic control and therefore also reduce the incidence of diabetic complications.
Immunological analysis of a Lactococcus lactis-based DNA vaccine expressing HIV gp120
Authors: Gram Gregers J , Fomsgaard Anders , Thorn Mette , Madsen Søren M , Glenting Jacob
Published: December 2019

For reasons of efficiencyEscherichia coliis used today as the microbial factory for production of plasmid DNA vaccines. To avoid hazardous antibiotic resistance genes and endotoxins from plasmid systems used nowadays, we have developed a system based on the food-gradeLactococcus lactisand a plasmid without antibiotic resistance genes. We compared theL. lactissystem to a traditional one inE. coliusing identical vaccine constructs encoding the gp120 of HIV-1. Transfection studies showed comparable gp120 expression levels using both vector systems. Intramuscular immunization of mice withL. lactisvectors developed comparable gp120 antibody titers as mice receivingE. colivectors. In contrast, the induction of the cytolytic response was lower using theL. lactisvector. Inclusion of CpG motifs in the plasmids increased T-cell activation more when theE. colirather than theL. lactisvector was used. This could be due to the different DNA content of the vector backbones. Interestingly, stimulation of splenocytes showed higher adjuvant effect of theL. lactisplasmid. The study suggests the developedL. lactisplasmid system as new alternative DNA vaccine system with improved safety features. The different immune inducing properties using similar gene expression units, but different vector backbones and production hosts give information of the adjuvant role of the silent plasmid backbone. The results also show that correlation between thein vitroadjuvanticity of plasmid DNA and its capacity to induce cellular and humoral immune responses in mice is not straight forward.
The effect of infliximab plus methotrexate on the modulation of inflammatory disease markers in juvenile idiopathic arthritis: analyses from a randomized, placebo-controlled trial
Authors: Visvanathan Sudha , Wagner Carrie , Marini Joseph C , Lovell Daniel J , Martini Alberto , Petty Ross , Cuttica Ruben , Woo Patricia , Espada Graciela , Gattorno Marco , Apaz Maria T , Baildam Eileen , Fasth Anders , Gerloni Valeria , Lahdenne Pekka , Quartier Pierre , Saurenmann Rotraud , Travers Suzanne , Mendelsohn Alan , Xu Stephen , Giannini Edward H , Ruperto Nicolino ,   the Paediatric Rheumatology INternational Trials Organization (PRINTO),   the Pediatric Rheumatology Collaborative Study Group (PRCSG)
Published: December 2019

Background

We evaluated the effect of infliximab on markers of inflammation in patients with juvenile idiopathic arthritis (JIA).

Methods

In this randomized, placebo-controlled substudy, 122 patients with JIA received infliximab 3 mg/kg + methotrexate (MTX)(n = 60) or placebo + MTX (n = 62) at weeks 0, 2, and 6. At week 14, patients receiving placebo + MTX crossed over to infliximab 6 mg/kg + MTX; patients receiving infliximab 3 mg/kg + MTX continued treatment through week 44. Sera and plasma from eligible patients receiving infliximab 3 mg/kg + MTX (n = 34) and receiving placebo→infliximab 6 mg/kg +MTX (n = 38) were collected at weeks 0, 2, 14, 16, 28, and 52 and analyzed for inflammatory markers (IL-6, IL-12p40, ICAM-1, MMP-3, VEGF, TNF-α, and CRP).

Results

At week 2, decreases from baseline in IL-6, ICAM-1, MMP-3, TNF-α, and CRP were greater with infliximab versus placebo treatment, and with the exception of CRP, these differences were generally maintained through week 14. The decreases from baseline to week 52 in IL-6, ICAM-1, VEGF, MMP-3, and CRP and increases in IL-12p40 levels were larger in patients receiving placebo→infliximab 6 mg/kg +MTX versus infliximab 3 mg/kg + MTX treatment. Patients receiving infliximab 3 mg/kg+MTX who achieved an American College of Rheumatology Pediatric 30 (ACR-Pedi-30) response had significantly larger decreases from baseline in ICAM-1 (p = 0.0105) and MMP-3 (p = 0.0253) at week 2 and in ICAM-1 (p = 0.0304), MMP-3 (p = 0.0091), and CRP (p = 0.0011) at week 14 versus ACR-Pedi-30 nonresponders.

Conclusion

Infliximab + MTX attenuated several inflammatory markers in patients with JIA; larger decreases in ICAM-1, MMP-3, and CRP levels were observed in ACR-Pedi-30 responders versus nonresponders.

Trial Registration

NCT00036374
Effects of betaine on lipopolysaccharide-induced memory impairment in mice and the involvement of GABA transporter 2
Authors: Miwa Masaya , Tsuboi Mizuki , Noguchi Yumiko , Enokishima Aoi , Nabeshima Toshitaka , Hiramatsu Masayuki
Published: December 2019

Background

Betaine (glycine betaine or trimethylglycine) plays important roles as an osmolyte and a methyl donor in animals. While betaine is reported to suppress expression of proinflammatory molecules and reduce oxidative stress in aged rat kidney, the effects of betaine on the central nervous system are not well known. In this study, we investigated the effects of betaine on lipopolysaccharide (LPS)-induced memory impairment and on mRNA expression levels of proinflammatory molecules, glial markers, and GABA transporter 2 (GAT2), a betaine/GABA transporter.

Methods

Mice were continuously treated with betaine for 13 days starting 1 day before they were injected with LPS, or received subacute or acute administration of betaine shortly before or after LPS injection. Then, their memory function was evaluated using Y-maze and novel object recognition tests 7 and 10-12 days after LPS injection (30 μg/mouse, i.c.v.), respectively. In addition, mRNA expression levels in hippocampus were measured by real-time RT-PCR at different time points.

Results

Repeated administration of betaine (0.163 mmol/kg, s.c.) prevented LPS-induced memory impairment. GAT2 mRNA levels were significantly increased in hippocampus 24 hr after LPS injection, and administration of betaine blocked this increase. However, betaine did not affect LPS-induced increases in levels of mRNA related to inflammatory responses. Both subacute administration (1 hr before, and 1 and 24 hr after LPS injection) and acute administration (1 hr after LPS injection) of betaine also prevented LPS-induced memory impairment in the Y-maze test.

Conclusions

These data suggest that betaine has protective effects against LPS-induced memory impairment and that prevention of LPS-induced changes in GAT2 mRNA expression is crucial to this ameliorating effect.
Characterization of aberrant pathways across human cancers
Authors: Ylipää Antti , Yli-Harja Olli , Zhang Wei , Nykter Matti
Published: December 2019

Background

Cancer is a broad group of genetic diseases which account for millions of deaths worldwide each year. Cancers are classified by various clinical, pathological and molecular methods, but even within a well-characterized disease, there is a significant inter-patient variability in survival, response to treatment, and other parameters. Especially in molecular level, tumours of the same category can appear significantly dissimilar due to complex combinations of genetic aberrations leading to a similar malignancy. We extended the current classification methods by studying tumour heterogeneity at pathway level.

Methods

We computed the rate of alterations in 1994 pathways and 2210 tumours consisting of eight different cancers. Using gene set enrichment analysis, each sample was computed a pathway aberration profile that reflected its molecular state. The profiles were analysed together to infer the characteristic aberration rates for each pathway within each cancer. Subgroups of tumours defined by similar pathway aberrations were identified using clustering analyses. The pathway aberration and gene expression profiles of the subgroups were consecutively compared across all eight cancer types to search for similar tumours crossing the standard classification.

Results

We identified pathways and processes that were common to all cancers as well as traits that are unique to a cancer type or closely related cancers. Studying the gene expression patterns within the pathway context suggested potential alteration mechanisms. Clustering analysis revealed five clinically relevant subgroups of tumours in four cancers that exhibited significant differences in survival compared to others. The cross-cancer analysis of the subgroups resulted in the identification of tumours that shared potentially significant alterations.

Conclusions

This study represents the first effort to extend the molecular characterizations towards pathway level descriptions across the family of cancers. In addition to providing a proof-of-concept for single sample pathway aberration analysis in this context, we present a comprehensive pathway aberration dataset that can be used to study pathway aberration patterns within or across cancers. Significant similarities between subgroups of different cancers on pathway and gene expression levels provide interesting hypotheses for understanding variable drug response, or transferring treatments across diseases by identifying common druggable pathways or genes, for example.
Biomarkers of disease differentiation: HCV recurrence versus acute cellular rejection
Authors: Gehrau Ricardo , Mas Valeria , Archer Kellie , Maluf Daniel
Published: December 2019

The wound-healing process induced by chronic hepatitis C virus (HCV) infection triggers liver damage characterized by fibrosis development and finally cirrhosis. Liver Transplantation (LT) is the optimal surgical treatment for HCV-cirrhotic patients at end-stage liver disease. However, acute cellular rejection (ACR) and HCV recurrence disease represent two devastating complications post-LT. The accurate differential diagnosis between both conditions is critical for treatment choice, and similar histological features represent a challenge for pathologists. Moreover, the HCV recurrence disease severity is highly variable post-LT. HCV recurrence disease progression is characterized by an accelerated fibrogenesis process, and almost 30% of those patients develop cirrhosis at 5-years of follow-up. Whole-genome gene expression (WGE) analyses through well-defined oligonucleotide microarray platforms represent a powerful tool for the molecular characterization of biological process. In the present manuscript, the utility of microarray technology is applied for the ACR and HCV-recurrence biological characterization in post-LT liver biopsy samples. Moreover, WGE analysis was performed to identify predictive biomarkers of HCV recurrence severity in formalin-fixed paraffin-embedded liver biopsies prospectively collected.
Development of a novel DNA sequencing method not only for hepatitis B virus genotyping but also for drug resistant mutation detection
Authors: Wang Fanjun , Lu Lili , Yu Changshun , Lv Zhanwu , Luo Xuelian , Wan Chao , Hu Zhaohui , Zhu Qinyi , Deng Youping , Zhang Chuyu
Published: December 2019

Background

In HBV-infected patients, different genotypes of the hepatitis B virus influence liver disease progression and response to antiviral therapy. Moreover, long-term antiviral therapy will eventually select for drug-resistant mutants. Detection of mutations associated to antiviral therapy and HBV genotyping are essential for monitoring treatment of chronic hepatitis B patients.

Results

In this study, a simple method of partial-S gene sequencing using a common PCR amplification was established for genotyping clinical HBV isolates sensitively, which could detect the drug-resistant mutations successfully at the same time.

Conclusions

The partial S gene sequencing assay developed in this study has potential for application in HBV genotyping and drug resistant mutation detection. It is simpler and more convenient than traditional S gene sequencing, but has nearly the same sensitivity and specificity when compared to S gene sequencing.
A single-tube allele specific-polymerase chain reaction to detect T315I resistant mutation in chronic myeloid leukemia patients
Authors: Wongboonma Wanwisa , Thongnoppakhun Wanna , Auewarakul Chirayu U
Published: December 2019

Background

BCR-ABL kinase domain (KD) mutation is the major mechanism contributing to suboptimal response to tyrosine kinase inhibitors (TKI) in BCR-ABL-positive chronic myeloid leukemia (CML) patients. T315I mutation, as one of the most frequent KD mutations, has been shown to be strongly associated with TKI resistance and subsequent therapeutic failure. A simple and sensitive method is thus required to detect T315I mutation at the earliest stage.

Methods

A single-tube allele specific-polymerase chain reaction (AS-PCR) method was developed to detect T315I mutation in a mixture of normal and mutant alleles of varying dilutions. Denaturing high performance liquid chromatography (DHPLC) and direct sequencing were performed as a comparison to AS-PCR.

Results

T315I mutant bands were observed in the mixtures containing as low as 0.5-1% of mutant alleles by AS-PCR. The detection sensitivity of DHPLC was around 1.5-3% dilution whereas sequencing analysis was unable to detect below 6.25% dilution.

Conclusion

A single-tube AS-PCR is a rapid and sensitive screening method for T315I mutation. Detection of the most resistant leukemic clone in CML patients undergoing TKI therapy should be feasible with this simple and inexpensive method.
Retrotransposon vectors for gene delivery in plants
Authors: Hou Yi , Rajagopal Jyothi , Irwin Phillip A , Voytas Daniel F
Published: December 2019

Background

Retrotransposons are abundant components of plant genomes, and although some plant retrotransposons have been used as insertional mutagens, these mobile genetic elements have not been widely exploited for plant genome manipulation. In vertebrates and yeast, retrotransposons and retroviruses are routinely altered to carry additional genes that are copied into complementary (c)DNA through reverse transcription. Integration of cDNA results in gene delivery; recombination of cDNA with homologous chromosomal sequences can create targeted gene modifications. Plant retrotransposon-based vectors, therefore, may provide new opportunities for plant genome engineering.

Results

A retrotransposon vector system was developed for gene delivery in plants based on the Tnt1 element from Nicotiana tabacum. Mini-Tnt1 transfer vectors were constructed that lack coding sequences yet retain the 5' and 3' long terminal repeats (LTRs) and adjacent cis sequences required for reverse transcription. The internal coding region of Tnt1 was replaced with a neomycin phosphotransferase gene to monitor replication by reverse transcription. Two different mini-Tnt1 s were developed: one with the native 5' LTR and the other with a chimeric 5' LTR that had the first 233 bp replaced by the CaMV 35 S promoter. After transfer into tobacco protoplasts, both vectors undergo retrotransposition using GAG and POL proteins provided in trans by endogenous Tnt1 elements. The transposition frequencies of mini-Tnt1 vectors are comparable with native Tnt1 elements, and like the native elements, insertion sites are within or near coding sequences. In this paper, we provide evidence that template switching occurs during mini-Tnt1 reverse transcription, indicating that multiple copies of Tnt1 mRNA are packaged into virus-like particles.

Conclusions

Our data demonstrate that mini-Tnt1 vectors can replicate efficiently in tobacco cells using GAG and POL proteins provided in trans by native Tnt1 elements. This suggests that helper Tnt1 constructs can be developed to enable a Tnt1-based two-component vector system that could be used in other plant species. Such a vector system may prove useful for gene delivery or the production of cDNA that can serve as a donor molecule for gene modification through homologous recombination.
Finding biomedical categories in Medline®
Authors: Yeganova Lana , Kim Won , Comeau Donald C , John Wilbur W
Published: December 2019

Background

There are several humanly defined ontologies relevant to Medline. However, Medline is a fast growing collection of biomedical documents which creates difficulties in updating and expanding these humanly defined ontologies. Automatically identifying meaningful categories of entities in a large text corpus is useful for information extraction, construction of machine learning features, and development of semantic representations. In this paper we describe and compare two methods for automatically learning meaningful biomedical categories in Medline. The first approach is a simple statistical method that uses part-of-speech and frequency information to extract a list of frequent nouns from Medline. The second method implements an alignment-based technique to learn frequent generic patterns that indicate a hyponymy/hypernymy relationship between a pair of noun phrases. We then apply these patterns to Medline to collect frequent hypernyms as potential biomedical categories.

Results

We study and compare these two alternative sets of terms to identify semantic categories in Medline. We find that both approaches produce reasonable terms as potential categories. We also find that there is a significant agreement between the two sets of terms. The overlap between the two methods improves our confidence regarding categories predicted by these independent methods.

Conclusions

This study is an initial attempt to extract categories that are discussed in Medline. Rather than imposing external ontologies on Medline, our methods allow categories to emerge from the text.
Indigenous fodder trees can increase grazing accessibility for landless and mobile pastoralists in northern Pakistan
Authors: Inam-ur-Rahim  , Maselli Daniel , Rueff Henri , Wiesmann Urs
Published: December 2019

Degraded hillsides in Northern Pakistan are rehabilitated through social forestry campaigns using fast growing exotic trees. These plantations on former scrublands curtail access by livestock owned by landless pastoralists and create social tension. This study proposes an alternative strategy of planting indigenous fodder trees and shrubs that are well-suited to the local socio-ecological characteristics and can benefit all social segments. The choice of fodder tree species, their nutritional value and distribution within the complex socio-ecological system is explained. This study also explores the suitability of these trees at different elevations, sites and transhumant routes. Providing mobile herders with adequate fodder trees could relax social tensions and complement food security.
Effects of zero reference position on bladder pressure measurements: an observational study
Authors: De Dios Soler Morejón Caridad , Lombardo Tomás Ariel , Tamargo Barbeito Teddy Osmin , Sandra Barquín García
Published: December 2019

Background

Although the World Society for Abdominal Compartment Syndrome in its guidelines recommends midaxillary line (MAL) as zero reference level in intra-abdominal pressure (IAP) measurements in aiming at standardizing the technique, evidence supporting this suggestion is scarce. The aim of this study is to study if the zero reference position influences bladder pressure measurements as estimate for IAP.

Methods

The IAP of 100 surgical patients was measured during the first 24 h of admission to the surgical intensive care unit of General Calixto Garcia Hospital in Havana (Cuba) following laparotomy. The period was January 2009 to January 2010. The IAP was measured twice with a six-hour interval using the transurethral technique with a priming volume of 25 ml. IAP was first measured with the zero reference level placed at MAL (IAPMAL), followed by a second measurement at the level of the symphysis pubis (SP) after 3 minutes (IAPSP). Correlations were made between IAP and body mass index (BMI), type of surgery, gender, and age.

Results

Mean IAPMALwas 8.5 ± 2.8 mmHg vs. IAPSP6.5 ± 2.8 mmHg (p< 0.0001). The bias between measurements was 2.0 ± 1.5, 95% confidence interval of 1.4 to 3.0, upper limit of 4.9, lower limit of -0.9, and a percentage error of 35.1%. IAPMALwas consistently higher than IAPSPregardless of the type of surgery. The BMI correlated with IAP values regardless of the zero reference level (R2= 0.4 and 0.3 with IAPMALand IAPSPrespectively,p< 0.0001).

Conclusions

The zero reference level has an important impact on IAP measurement in surgical patients after laparotomy and can potentially lead to over or underestimation. Further anthropometric studies are needed with regard to the relative MAL and SP zero reference position in relation to the theoretical ideal reference level at midpoint of the abdomen. Until better evidence is available, MAL remains the recommended zero reference position due to its best anatomical localization at iliac crest.
Pediatric critical care nurses' experience with abdominal compartment syndrome
Authors: Newcombe Jennifer , Mathur Mudit , Bahjri Khaled , Ejike J Chiaka
Published: December 2019

Background

Abdominal compartment syndrome (ACS) is a syndrome associated with multi-system effects of elevated intra-abdominal pressure (IAP) in critically ill children. It has a 90-100% mortality rate if not recognized and treated promptly. Measuring IAP helps identify patients developing intra-abdominal hypertension (IAH) which allows for timely intervention before progression to ACS. IAP helps identify ACS and guides its medical and surgical management. IAP is often measured by the bedside nurse in the intensive care unit. Pediatric critical care nurses (PCCN) play a key role in managing critically ill patients and recognizing potential causes for clinical deterioration such as ACS therefore should be knowledgeable about this entity.

Objective

The aim of this study was to assess the awareness and current knowledge of ACS among PCCN.

Methods

A ten-item written questionnaire was distributed at a National Critical Care Conference in 2006 and again in 2010. Participants of the conference voluntarily completed and immediately returned the survey. Results from the two questionnaires were compared.

Results

Sixty-two percent of 691 questionnaires were completed. The awareness of ACS improved from 69.3% in 2006 to 87.8% in 2010 (p < 0.001) among PCCN. "Years in practice" influenced awareness of ACS. Nurses working for 5-10 and > 10 years were, respectively, 2.34 and 1.89 times more likely to be aware of ACS than those working for < 5 years. Hands-on experience managing a child with ACS by PCCN also improved from 49.1% to 67.9% (p < 0.001) but remains low. The number of participants who never measured IAP fell from 27.3% to 19.1% (p = 0.101). The most common method being used to measure IAP is the bladder method. Knowledge of the definition of ACS remains poor with only 13.2% associating the definition of ACS with organ dysfunction in 2010 which was even lower than in 2006.

Conclusions

There is increasing awareness of ACS and experience in its management among PCCN. However, few PCCN correctly understand the definition of ACS. Since recognition of IAH and early intervention can reduce morbidity and mortality in critically ill patients, further educational efforts should be directed toward improving the knowledge and recognition of ACS by PCCN.
Treatment with the arginase inhibitor Nw-hydroxy-nor-L-arginine restores endothelial function in rat adjuvant-induced arthritis
Authors: Prati Clément , Berthelot Alain , Kantelip Bernadette , Wendling Daniel , Demougeot Céline
Published: December 2019

Introduction

Endothelial dysfunction (ED) participates to atherogenesis associated to rheumatoid arthritis. We recently reported increased arginase activity/expression in vessels from adjuvant-induced arthritis (AIA) rats. In the present study, we investigated the effects of a curative treatment with the arginase inhibitor Nw-hydroxy-nor-L-arginine (nor-NOHA) on vascular dysfunction in AIA rats.

Methods

AIA rats were treated with nor-NOHA (40 mg/kg/d, ip) for 21 days after the onset of arthritis. A group of untreated AIA rats and a group of healthy rats served as controls. ED was assessed by the vasodilatory effect of acetylcholine (Ach) on aortic rings. The role of superoxide anions, prostanoids, endothelium-derived hyperpolarizing factor (EDHF) and nitric oxide synthase (NOS) pathway was studied. Plasma levels of IL-6 and vascular endothelial growth factor (VEGF) were determined by ELISA kits. Arthritis severity was estimated by a clinical, radiological and histological analysis.

Results

Nor-NOHA treatment fully restored the aortic response to Ach to that of healthy controls. The results showed that this beneficial effect is mediated by an increase in NOS activity and EDHF and reduced superoxide anion production as well as a decrease in the activity of cyclooxygenase (COX)-2, thromboxane and prostacyclins synthases. In addition, nor-NOHA decreased IL-6 and VEGF plasma levels in AIA rats. By contrast, the treatment did not modify arthritis severity in AIA rats.

Conclusions

The treatment with an arginase inhibitor has a potent effect on ED in AIA independently of the severity of the disease. Our results suggest that this new pharmacological approach has the potential as a novel add-on therapy in the treatment of RA.
Parenteral nutrition: never say never
Authors: Oshima Taku , Pichard Claude
Published: December 2019

This review emphasizes the benefits of parenteral nutrition (PN) in critically ill patients, when prescribed for relevant indications, in adequate quantities, and in due time.

Critically ill patients are at risk of energy deficit during their ICU stay, a condition which leads to unfavorable outcomes, due to hypercatabolism secondary to the stress response and the difficulty to optimize feeding. Indirect calorimetry is recommended to define the energy target, since no single predictive equation accurately estimates energy expenditure. Energy metabolism is intimately associated with protein metabolism. Recent evidence calls for adequate protein provision, but there is no accurate method to estimate the protein requirements, and recommendations are probably suboptimal. Enteral nutrition (EN) is the preferred route of feeding, but gastrointestinal intolerance limits its efficacy and PN allows for full coverage of energy needs.

Seven recent articles concerning PN for critically ill patients were identified and carefully reviewed for the clinical and scientific relevance of their conclusions. One article addressed the unfavorable effects of early PN, although this result should be more correctly regarded as a consequence of glucose load and hypercaloric feeding. The six other articles were either in favor of PN or concluded that there was no difference in the outcome compared with EN. Hypercaloric feeding was not observed in these studies. Hypocaloric feeding led to unfavorable outcomes. This further demonstrates the beneficial effects of an early and adequate feeding with full EN, or in case of failure of EN with exclusive or supplemental PN.

EN is the first choice for critically ill patients, but difficulties providing optimal nutrition through exclusive EN are frequently encountered. In cases of insufficient EN, individualized supplemental PN should be administered to reduce the infection rate and the duration of mechanical ventilation. PN is a safe therapeutic option as long as sufficient attention is given to avoid hypercaloric feeding.
Hemodynamic coherence and the rationale for monitoring the microcirculation
Authors: Ince Can
Published: December 2019

This article presents a personal viewpoint of the shortcoming of conventional hemodynamic resuscitation procedures in achieving organ perfusion and tissue oxygenation following conditions of shock and cardiovascular compromise, and why it is important to monitor the microcirculation in such conditions. The article emphasizes that if resuscitation procedures are based on the correction of systemic variables, there must be coherence between the macrocirculation and microcirculation if systemic hemodynamic-driven resuscitation procedures are to be effective in correcting organ perfusion and oxygenation. However, in conditions of inflammation and infection, which often accompany states of shock, vascular regulation and compensatory mechanisms needed to sustain hemodynamic coherence are lost, and the regional circulation and microcirculation remain in shock. We identify four types of microcirculatory alterations underlying the loss of hemodynamic coherence: type 1, heterogeneous microcirculatory flow; type 2, reduced capillary density induced by hemodilution and anemia; type 3, microcirculatory flow reduction caused by vasoconstriction or tamponade; and type 4, tissue edema. These microcirculatory alterations can be observed at the bedside using direct visualization of the sublingual microcirculation with hand-held vital microscopes. Each of these alterations results in oxygen delivery limitation to the tissue cells despite the presence of normalized systemic hemodynamic variables. Based on these concepts, we propose how to optimize the volume of fluid to maximize the oxygen-carrying capacity of the microcirculation to transport oxygen to the tissues.
Challenges and pitfalls when implementing renal replacement therapy in the ICU
Authors: Mehta Ravindra L
Published: December 2019

Several new methods of renal replacement therapy (RRT) are now available for treating patients in the ICU setting. However, utilization of RRT in the ICU is subject to considerable variation and the need for RRT is associated with worse outcomes. Several factors influence the application of dialysis and reflect the interplay of patient and process of care elements that are dynamic in nature. Despite multiple studies evaluating RRT and its application, there are gaps in our knowledge that must be overcome to improve outcomes. This article discusses some of the important issues that require attention in delivering RRT in critically ill patients and provides a framework for the optimal use of RRT in the ICU.
Central venous oxygen saturation and blood lactate levels during cardiopulmonary bypass are associated with outcome after pediatric cardiac surgery
Authors: Ranucci Marco , Isgrò Giuseppe , Carlucci Concetta , De La Torre Teresa , Enginoli Stefania , Frigiola Alessandro ,   Surgical and Clinical Outcome REsearch (SCORE) Group
Published: December 2019

Introduction

Central venous oxygen saturation and blood lactate are different indices of the adequacy of oxygen delivery to the oxygen needs. In pediatric cardiac surgery, lactate level and kinetics during and after cardiopulmonary bypass are associated with outcome variables. The aim of this study was to explore the hypothesis that the lowest central venous oxygen saturation and the peak lactate value during cardiopulmonary bypass, used alone or in combination, may be predictive of major morbidity and mortality in pediatric cardiac surgery.

Methods

We conducted a retrospective analysis of 256 pediatric (younger than 6 years) patients who had undergone cardiac surgery with continuous monitoring of central venous oxygen saturation and serial measurement of blood lactate.

Results

Peak lactate was significantly increased when the nadir central venous oxygen saturation was < 68%. Both nadir central venous oxygen saturation and peak lactate during cardiopulmonary bypass were independently associated with major morbidity and mortality, with the same accuracy for major morbidity and a higher accuracy of peak lactate for mortality. A combined index (central venous oxygen saturation < 68% and peak lactate > 3 mmol/L) provided the highest sensitivity and specificity for major morbidity, with a positive predictive value of 89%.

Conclusions

The combination of a continuous monitoring of central venous oxygen saturation and serial measurements of blood lactate during cardiopulmonary bypass may offer a predictive index for major morbidity after cardiac operations in pediatric patients. This study generates the hypothesis that strategies aimed to preserve oxygen delivery during cardiopulmonary bypass may reduce the occurrence of low values of central venous oxygen saturation and elevated lactate levels. Further studies should consider this hypothesis and take into account other time-related factors, such as time of exposure to low values of central venous oxygen saturation and kinetics of lactate formation.
Recognizing ion ligand binding sites by SMO algorithm
Authors: Wang Shan , Hu Xiuzhen , Feng Zhenxing , Zhang Xiaojin , Liu Liu , Sun Kai , Xu Shuang
Published: December 2019

Background

In many important life activities, the execution of protein function depends on the interaction between proteins and ligands. As an important protein binding ligand, the identification of the binding site of the ion ligands plays an important role in the study of the protein function.

Results

In this study, four acid radical ion ligands (NO2−,CO32−,SO42−,PO43−) and ten metal ion ligands (Zn2+,Cu2+,Fe2+,Fe3+,Ca2+,Mg2+,Mn2+,Na+,K+,Co2+) are selected as the research object, and the Sequential minimal optimization (SMO) algorithm based on sequence information was proposed, better prediction results were obtained by 5-fold cross validation.

Conclusions

An efficient method for predicting ion ligand binding sites was presented.
Patient and system factors associated with unassisted and injurious falls in hospitals: an observational study
Authors: Venema Dawn M. , Skinner Anne M. , Nailon Regina , Conley Deborah , High Robin , Jones Katherine J.
Published: December 2019

Background

Unassisted falls are more likely to result in injury than assisted falls. However, little is known about risk factors for falling unassisted. Furthermore, rural hospitals, which care for a high proportion of older adults, are underrepresented in research on hospital falls. This study identified risk factors for unassisted and injurious falls in rural hospitals.

Methods

Seventeen hospitals reported 353 falls over 2 years. We categorized falls by type (assisted vs. unassisted) and outcome (injurious vs. non-injurious). We used multivariate logistic regression to determine factors that predicted fall type and outcome.

Results

With all other factors being equal, the odds of falling unassisted were 2.55 times greater for a patient aged ≥65 than < 65 (95% confidence interval [CI] = 1.30–5.03), 3.70 times greater for a patient with cognitive impairment than without (95% CI = 2.06–6.63), and 6.97 times greater if a gait belt was not identified as an intervention for a patient than if it was identified (95% CI = 3.75–12.94). With all other factors being equal, the odds of an injurious fall were 2.55 times greater for a patient aged ≥65 than < 65 (95% CI = 1.32–4.94), 2.48 times greater if a fall occurred in the bathroom vs. other locations (95% CI = 1.41–4.36), and 3.65 times greater if the fall occurred when hands-on assistance was provided without a gait belt, compared to hands-on assistance with a gait belt (95% CI = 1.34–9.97).

Conclusions

Many factors associated with unassisted or injurious falls in rural hospitals were consistent with research conducted in larger facilities. A novel finding is that identifying a gait belt as an intervention decreased the odds of patients falling unassisted. Additionally, using a gait belt during an assisted fall decreased the odds of injury. We expanded upon other research that found an association between assistance during falls and injury by discovering that the manner in which a fall is assisted is an important consideration for risk mitigation.