bluuebunny/crossref_metadata_2025 huggingface dataset:
A comparison of curated gene sets versus transcriptomics-derived gene signatures for detecting pathway activation in immune cells
Authors: Liu Bin , Lindner Patrick , Jirmo Adan Chari , Maus Ulrich , Illig Thomas , DeLuca David S.
Published: January 2020

Background

Despite the significant contribution of transcriptomics to the fields of biological and biomedical research, interpreting long lists of significantly differentially expressed genes remains a challenging step in the analysis process. Gene set enrichment analysis is a standard approach for summarizing differentially expressed genes into pathways or other gene groupings. Here, we explore an alternative approach to utilizing gene sets from curated databases. We examine the method of deriving custom gene sets which may be relevant to a given experiment using reference data sets from previous transcriptomics studies. We call these data-derived gene sets, “gene signatures” for the biological process tested in the previous study. We focus on the feasibility of this approach in analyzing immune-related processes, which are complicated in their nature but play an important role in the medical research.

Results

We evaluate several statistical approaches to detecting the activity of a gene signature in a target data set. We compare the performance of the data-derived gene signature approach with comparable GO term gene sets across all of the statistical tests. A total of 61 differential expression comparisons generated from 26 transcriptome experiments were included in the analysis. These experiments covered eight immunological processes in eight types of leukocytes. The data-derived signatures were used to detect the presence of immunological processes in the test data with modest accuracy (AUC = 0.67). The performance for GO and literature based gene sets was worse (AUC = 0.59). Both approaches were plagued by poor specificity.

Conclusions

When investigators seek to test specific hypotheses, the data-derived signature approach can perform as well, if not better than standard gene-set based approaches for immunological signatures. Furthermore, the data-derived signatures can be generated in the cases that well-defined gene sets are lacking from pathway databases and also offer the opportunity for defining signatures in a cell-type specific manner. However, neither the data-derived signatures nor standard gene-sets can be demonstrated to reliably provide negative predictions for negative cases. We conclude that the data-derived signature approach is a useful and sometimes necessary tool, but analysts should be weary of false positives.
Exploring the metabolomic diversity of plant species across spatial (leaf and stem) components and phylogenic groups
Authors: Lee Sunmin , Oh Dong-Gu , Singh Digar , Lee Jong Seok , Lee Sarah , Lee Choong Hwan
Published: January 2020

Background

Plants have been used as an important source of indispensable bioactive compounds in various cosmetics, foods, and medicines. However, the subsequent functional annotation of these compounds seems arduous because of the largely uncharacterized, vast metabolic repertoire of plant species with known biological phenotypes. Hence, a rapid multi-parallel screening and characterization approach is needed for plant functional metabolites.

Results

Fifty-one species representing three plant families, namely Asteraceae, Fabaceae, and Rosaceae, were subjected to metabolite profiling using gas chromatography time-of-flight mass spectrometry (GC-TOF-MS) and ultrahigh-performance liquid chromatography quadrupole orbitrap ion trap tandem mass spectrometry (UHPLC-Q-orbitrap-MS/MS) as well as multivariate analyses. Partial least squares discriminant analysis (PLS-DA) of the metabolite profiling datasets indicated a distinct clustered pattern for 51 species depending on plant parts (leaves and stems) and relative phylogeny. Examination of their relative metabolite contents showed that the extracts from Fabaceae plants were abundant in amino acids, fatty acids, and genistein compounds. However, the extracts from Rosaceae had higher levels of catechin and ellagic acid derivatives, whereas those from Asteraceae were higher in kaempferol derivatives and organic acids. Regardless of the different families, aromatic amino acids, branch chain amino acids, chlorogenic acid, flavonoids, and phenylpropanoids related to the shikimate pathway were abundant in leaves. Alternatively, certain amino acids (proline, lysine, and arginine) as well as fatty acids levels were higher in stem extracts. Further, we investigated the associated phenotypes, i.e., antioxidant activities, affected by the observed spatial (leaves and stem) and intra-family metabolomic disparity in the plant extracts. Pearson’s correlation analysis indicated that ellagic acid, mannitol, catechin, epicatechin, and quercetin derivatives were positively correlated with antioxidant phenotypes, whereas eriodictyol was positively correlated with tyrosinase inhibition activity.

Conclusions

This work suggests that metabolite profiling, including multi-parallel approaches and integrated bioassays, may help the expeditious characterization of plant-derived metabolites while simultaneously unraveling their chemodiversity.
A sense of place: transcriptomics identifies environmental signatures in Cabernet Sauvignon berry skins in the late stages of ripening
Authors: Cramer Grant R. , Cochetel Noé , Ghan Ryan , Destrac-Irvine Agnès , Delrot Serge
Published: January 2020

Background

Grape berry ripening is influenced by climate, the main component of the “terroir” of a place. Light and temperature are major factors in the vineyard that affect berry development and fruit metabolite composition.

Results

To better understand the effect of “place” on transcript abundance during the late stages of berry ripening, Cabernet Sauvignon berries grown in Bordeaux and Reno were compared at similar sugar levels (19 to 26 °Brix (total soluble solids)). Day temperatures were warmer and night temperatures were cooler in Reno. °Brix was lower in Bordeaux berries compared to Reno at maturity levels considered optimum for harvest. RNA-Seq analysis identified 5528 differentially expressed genes between Bordeaux and Reno grape skins at 22°Brix. Weighted Gene Coexpression Network Analysis for all expressed transcripts for all four °Brix levels measured indicated that the majority (75%) of transcript expression differed significantly between the two locations. Top gene ontology categories for the common transcript sets were translation, photosynthesis, DNA metabolism and catabolism. Top gene ontology categories for the differentially expressed genes at 22°Brix involved response to stimulus, biosynthesis and response to stress. Some differentially expressed genes encoded terpene synthases, cell wall enzymes, kinases, transporters, transcription factors and photoreceptors. Most circadian clock genes had higher transcript abundance in Bordeaux. Bordeaux berries had higher transcript abundance with differentially expressed genes associated with seed dormancy, light, auxin, ethylene signaling, powdery mildew infection, phenylpropanoid, carotenoid and terpenoid metabolism, whereas Reno berries were enriched with differentially expressed genes involved in water deprivation, cold response, ABA signaling and iron homeostasis.

Conclusions

Transcript abundance profiles in the berry skins at maturity were highly dynamic. RNA-Seq analysis identified a smaller (25% of total) common core set of ripening genes that appear not to depend on rootstock, vineyard management, plant age, soil and climatic conditions. Much of the gene expression differed between the two locations and could be associated with multiple differences in environmental conditions that may have affected the berries in the two locations; some of these genes may be potentially controlled in different ways by the vinegrower to adjust final berry composition and reach a desired result.
Alterations in gut microbiota of abdominal aortic aneurysm mice
Authors: Xie Jiahe , Lu Weiling , Zhong Lintao , Hu Yuhua , Li Qingrui , Ding Rongming , Zhong Zhonggao , Liu Ziyou , Xiao Hai , Xie Dongming , Zheng Guofu , Ye Bo , Zhong Yiming , Liu Zuheng
Published: January 2020

Background

The gut microbiome plays an important role in various cardiovascular diseases, such as atherosclerosis and hypertension, which are associated with abdominal aortic aneurysms (AAAs).

Methods

Here, we used 16S rRNA sequencing to explore gut microbiota in C57BL ApoE−/− mice with AAAs. A mouse model of abdominal aortic aneurysms was induced with angiotensin II (Ang II) (1000 ng/min per kg). On day 28 after the operation, fecal samples were collected and stored at − 80 °C until DNA extraction. We determined the relative abundances of bacterial taxonomic groups using 16S rRNA amplicon metabarcoding, and sequences were analyzed using a combination of mother software and UPARSE.

Results

We found that the gut microbiome was different between control and AAA mice. The results of correlation analysis between AAA diameter and the gut microbiome as well as LEfSe of the genera Akkermansia, Odoribacter, Helicobacter and Ruminococcus might be important in the progression of AAAs.

Conclusions

AAA mice is subjected to gut microbial dysbiosis, and gut microbiota might be a potential target for further investigation.
Does potentially inappropriate prescribing predict an increased risk of admission to hospital and mortality? A longitudinal study of the ‘oldest old’
Authors: Cardwell Karen , Kerse Ngaire , Hughes Carmel M. , Teh Ruth , Moyes Simon A. , Menzies Oliver , Rolleston Anna , Broad Joanna B. , Ryan Cristín
Published: January 2020

Background

Potentially inappropriate prescribing (PIP) is associated with negative health outcomes, including hospitalisation and mortality. Life and Living in Advanced Age: a Cohort Study in New Zealand (LiLACS NZ) is a longitudinal study of Māori (the indigenous population of New Zealand) and non-Māori octogenarians. Health disparities between indigenous and non-indigenous populations are prevalent internationally and engagement of indigenous populations in health research is necessary to understand and address these disparities. Using LiLACS NZ data, this study reports the association of PIP with hospitalisations and mortality prospectively over 36-months follow-up.

Methods

PIP, from pharmacist applied criteria, was reported as potentially inappropriate medicines (PIMs) and potential prescribing omissions (PPOs). The association between PIP and hospitalisations (all-cause, cardiovascular disease-specific and ambulatory-sensitive) and mortality was determined throughout a series of 12-month follow-ups using binary logistic (hospitalisations) and Cox (mortality) regression analysis, reported as odds ratios (ORs) and hazard ratios (HRs), respectively, and the corresponding confidence intervals (CIs).

Results

Full demographic data were obtained for 267 Māori and 404 non-Māori at baseline, 178 Māori and 332 non-Māori at 12-months, and 122 Māori and 281 non-Māori at 24-months. The prevalence of any PIP (i.e. ≥1 PIM and/or PPO) was 66, 75 and 72% for Māori at baseline, 12-months and 24-months, respectively. In non-Māori, the prevalence of any PIP was 62, 71 and 73% at baseline, 12-months and 24-months, respectively. At each time-point, there were more PPOs than PIMs; at baseline Māori were exposed to a significantly greater proportion of PPOs compared to non-Māori (p = 0.02). In Māori: PPOs were associated with a 1.5-fold increase in hospitalisations and mortality. In non-Māori, PIMs were associated with a double risk of mortality.

Conclusions

PIP was associated with an increased risk of hospitalisation and mortality in this cohort. Omissions appear more important for Māori in predicting hospitalisations, and PIMs were more important in non-Māori in predicting mortality. These results suggest understanding prescribing outcomes across and between population groups is needed and emphasises prescribing quality assessment is useful.
Retrospective analysis of acute HBV infections occurred in 1978–79 and 1994–95 in North-East Italy: increasing prevalence of BCP/pre-core mutants in sub-genotype D3
Authors: Bruni Roberto , Villano Umbertina , Taffon Stefania , Equestre Michele , Madonna Elisabetta , Chionne Paola , Candido Angela , Dettori Stefano , Pisani Giulio , Rapicetta Maria , Bortolotti Flavia , Ciccaglione Anna Rita
Published: January 2020

Background

At the end of the 1970s, in Italy more than 2% of the general population was HBsAg carrier. In the late ‘70s and late ‘80s, two remarkable events might have impacted on HBV strains transmitted in North-East Italy: (a) the increased HBV incidence due to parenteral drugs between 1978 and 1982; (b) the preventive anti-HIV educational campaign, started locally in 1985.

Methods

To address if those events impacted on circulating HBV variants, acute cases occurred in North-East Italy in 1978–79 (n = 50) and 1994–95 (n = 30) were retrospectively analysed. HBV sequences obtained from serum samples were subjected to phylogenetic analysis and search for BCP/pre-core and S mutations.

Results

HBV-D was the most prevalent genotype in both 1978–79 (43/50, 86%) and 1994–95 (24/30, 80.0%), with HBV-A in all but one remaining cases. Among HBV-D cases, sub-genotype HBV-D3 was the most prevalent (25/29, 86.2% in 1978–79; 13/16, 81.2% in 1994–95), with HBV-D1 and HBV-D2 in the remaining cases. All HBV-A cases were sub-genotype A2.

Single and multiple BCP/pre-core mutations, responsible for HBeAg(−) hepatitis, were detected in 6/50 (12%) cases in 1978/79 vs. 12/30 (40.0%) in 1994/95 (p = 0.006). They were found exclusively in HBV-D; in the most abundant sub-genotype, HBV-D3, they were detected in 2/25 (8%) cases in 1978–79 vs. 6/13 (46%) in 1994–95 (p = 0.011). No vaccine escape S mutations were observed. The IDU risk factor was significantly more frequent in 1994–95 (8/30, 26.7%) than in 1978–79 (4/50, 8%) (p = 0.048).

Conclusions

The above mentioned epidemiological and public health events did not affect the proportion of genotypes and sub-genotypes that remained unchanged over 16 years. In contrast, the proportion of BCP/pre-core mutants increased more than three-fold, mostly in HBV-D3, a sub-genotype highly circulating in IDUs; drug abuse likely contributed to the spread of these mutants.

The findings contribute to explain a previously described major change in HBV epidemiology in Italy: the proportion of HBeAg(−) cases in the carrier cohort changed from low in late 1970s, to high at the beginning of the 2000s. In addition to other recognized factors, the increased circulation of BCP/pre-core mutants likely represents a further factor that contributed to this change.
Use of a rapid recombinase-aided amplification assay for Mycoplasma pneumoniae detection
Authors: Xue Guanhua , Li Shaoli , Zhao Hanqing , Yan Chao , Feng Yanling , Cui Jinghua , Jiang Tingting , Yuan Jing
Published: January 2020

Background

Mycoplasma pneumoniae is one of the most common causative pathogens of community-acquired pneumonia (CAP), accounting for as many as 30–50% of CAP during peak years. An early and rapid diagnostic method is key for guiding clinicians in their choice of antibiotics.

Methods

The recombinase-aided amplification (RAA) assay is a recently developed, rapid detection method that has been used for the detection of several pathogens. The assays were performed in a one-step single tube reaction at 39° Celsius within 15–30 min. In this study, we established an RAA assay for M. pneumoniae using clinical specimens for validation and commercial real-time PCR as the reference method.

Results

The analytical sensitivity of the RAA assay was 2.23 copies per reaction, and no cross-reactions with any of the other 15 related respiratory bacterial pathogens were observed. Compared with the commercial real-time PCR assay used when testing 311 respiratory specimens, the RAA assay obtained 100% sensitivity and 100% specificity with a kappa value of 1.

Conclusions

These results demonstrate that the proposed RAA assay will be of benefit as a faster, sensitive, and specific alternative tool for the detection of M. pneumoniae.
Exoskeleton for post-stroke recovery of ambulation (ExStRA): study protocol for a mixed-methods study investigating the efficacy and acceptance of an exoskeleton-based physical therapy program during stroke inpatient rehabilitation
Authors: Louie Dennis R. , Mortenson William B. , Durocher Melanie , Teasell Robert , Yao Jennifer , Eng Janice J.
Published: January 2020

Background

The ability to walk is commonly reported as a top rehabilitation priority for individuals after a stroke. However, not all individuals with stroke are able to practice walking, especially those who require more assistance from their therapist to do so. Powered robotic exoskeletons are a new generation of robotic-assisted gait training devices, designed to assist lower extremity movement to allow repetitious overground walking practice. To date, minimal research has been conducted on the use of an exoskeleton for gait rehabilitation after stroke. The following research protocol aims to evaluate the efficacy and acceptability, and thus adoptability, of an exoskeleton-based gait rehabilitation program for individuals with stroke.

Methods

This research protocol describes a prospective, multi-center, mixed-methods study comprised of a randomized controlled trial and a nested qualitative study. Forty adults with subacute stroke will be recruited from three inpatient rehabilitation hospitals and randomized to receive either the exoskeleton-based gait rehabilitation program or usual physical therapy care. The primary outcome measure is the Functional Ambulation Category at post-intervention, and secondary outcomes include motor recovery, functional mobility, cognitive, and quality-of-life measures. Outcome data will be collected at baseline, post-intervention, and at 6 months. The qualitative component will explore the experience and acceptability of using a powered robotic exoskeleton for stroke rehabilitation from the point of view of individuals with stroke and physical therapists. Semi-structured interviews will be conducted with participants who receive the exoskeleton intervention, and with the therapists who provide the intervention. Qualitative data will be analyzed using interpretive description.

Discussion

This study will be the first mixed-methods study examining the adoptability of exoskeleton-based rehabilitation for individuals with stroke. It will provide valuable information regarding the efficacy of exoskeleton-based training for walking recovery and will shed light on how physical therapists and patients with stroke perceive the device. The findings will help guide the integration of robotic exoskeletons into clinical practice.

Trial registration

NCT02995265 (clinicaltrials.gov), Registered 16 December 2016.
High-risk behaviors and their association with awareness of HIV status among participants of a large-scale prevention intervention in Athens, Greece
Authors: Pavlopoulou Ioanna D. , Dikalioti Stavroula K. , Gountas Ilias , Sypsa Vana , Malliori Meni , Pantavou Katerina , Jarlais Don Des , Nikolopoulos Georgios K. , Hatzakis Angelos
Published: January 2020

Background

Aristotle was a seek-test-treat intervention during an outbreak of human immunodeficiency virus (HIV) infection among people who inject drugs (PWID) in Athens, Greece that started in 2011. The aims of this analysis were: (1) to study changes of drug injection-related and sexual behaviors over the course of Aristotle; and (2) to compare the likelihood of risky behaviors among PWID who were aware and unaware of their HIV status.

Methods

Aristotle (2012–2013) involved five successive respondent-driven sampling rounds of approximately 1400 PWID each; eligible PWID could participate in multiple rounds. Participants were interviewed using a questionnaire, were tested for HIV, and were classified as HIV-positive aware of their status (AHS), HIV-positive unaware of their status (UHS), and HIV-negative. Piecewise linear generalized estimating equation models were used to regress repeatedly measured binary outcomes (high-risk behaviors) against covariates.

Results

Aristotle recruited 3320 PWID (84.5% males, median age 34.2 years). Overall, 7110 interviews and blood samples were collected. The proportion of HIV-positive first-time participants who were aware of their HIV infection increased from 21.8% in round A to 36.4% in the last round. The odds of dividing drugs at least half of the time in the past 12 months with a syringe someone else had already used fell from round A to B by 90% [Odds Ratio (OR) (95% Confidence Interval-CI): 0.10 (0.04, 0.23)] among AHS and by 63% among UHS [OR (95% CI): 0.37 (0.19, 0.72)]. This drop was significantly larger (p = 0.02) among AHS. There were also decreases in frequency of injection and in receptive syringe sharing in the past 12 months but they were not significantly different between AHS (66 and 47%, respectively) and UHS (63 and 33%, respectively). Condom use increased only among male AHS from round B to the last round [OR (95% CI): 1.24 (1.01, 1.52)].

Conclusions

The prevalence of risky behaviors related to drug injection decreased in the context of Aristotle. Knowledge of HIV infection was associated with safer drug injection-related behaviors among PWID. This highlights the need for comprehensive interventions that scale-up HIV testing and help PWID become aware of their HIV status.
Generation of recombinant baculovirus expressing atoxic C-terminal CPA toxin of Clostridium perfringens and production of specific antibodies
Authors: Forti Katia , Cagiola Monica , Pellegrini Martina , Anzalone Lucia , Di Paolo Antonella , Corneli Sara , Severi Giulio , De Giuseppe Antonio
Published: January 2020

Background

Clostridium perfringensis the causative agent of several diseases and enteric infections in animals and humans. The virulence ofC. perfringensis largely attributable to the production of numerous toxins; of these, the alpha toxin (CPA) plays a crucial role in histotoxic infections (gas gangrene). CPA toxin consists of two domains, i.e., the phospholipase C active site, which lies in the N-terminal domain amino acid (aa residues 1–250), and the C-terminal region (aa residues 251–370), which is responsible for the interaction of the toxin with membrane phospholipids in the presence of calcium ions. All currently produced clostridial vaccines contain toxoids derived from culture supernatants that are inactivated, mostly using formalin. The CPA is an immunogenic antigen; recently, it has been shown that mice that were immunized with the C-terminal domain of the toxin produced inE. coliwere protected againstC. perfringensinfections and the anti-sera produced were able to inhibit the CPA activity. Monoclonal and polyclonal antibodies were produced only against full-length CPA and not against the truncated forms.

Results

In the present study, we have reported for the first time; about the generation of a recombinant baculovirus capable of producing a deleted rCPA toxin (rBacCPA250–363H6) lacking the N-terminal domain and the 28 amino acids (aa) of the putative signal sequence. The insertion of theL21consensus sequence upstream of the translational start codon ATG, drastically increases the yield of recombinant protein in the baculovirus-based expression system. The protein was purified by Ni-NTA affinity chromatography and the lack of toxicity in vitro was confirmed in CaCo-2 cells. Polyclonal antibodies and eight hybridoma-secreting Monoclonal antibodies were generated and tested to assess specificity and reactivity. The anti-sera obtained against the fragment rBacCPA250–363H6 neutralized the phospholipase C activity of full-length PLC.

Conclusions

TheL21leader sequence enhanced the expression of atoxic C-terminal recombinant CPA protein produced in insect cells. The monoclonal and polyclonal antibodies obtained were specific and highly reactive. The availability of these biologicals could contribute to the development of diagnostic assays and/or new recombinant protein vaccines.
Usage of cloud storage facilities by medical students in a low-middle income country, Sri Lanka: a cross sectional study
Authors: Hettige Samankumara , Dasanayaka Eshani , Ediriweera Dileepa Senajith
Published: January 2020

Background

Cloud storage facilities (CSF) has become popular among the internet users. There is limited data on CSF usage among university students in low middle-income countries including Sri Lanka. In this study we present the CSF usage among medical students at the Faculty of Medicine, University of Kelaniya.

Methods

We undertook a cross sectional study at the Faculty of Medicine, University of Kelaniya, Sri Lanka. Stratified random sampling was used to recruit students representing all the batches. A self-administrated questionnaire was given.

Results

Of 261 (90.9%) respondents, 181 (69.3%) were females. CSF awareness was 56.5% (95%CI: 50.3–62.6%) and CSF usage was 50.8% (95%CI: 44.4–57.2%). Awareness was higher in males (P = 0.003) and was low in senior students. Of CSF aware students, 85% knew about Google Drive and 70.6% used it. 73.6 and 42.1% knew about Dropbox and OneDrive. 50.0 and 22.0% used them respectively. There was no association between CSF awareness and pre-university entrance or undergraduate examination performance. Inadequate knowledge, time, accessibility, security and privacy concerns limited CSF usage. 69.8% indicated that they would like to undergo training on CSF as an effective tool for education.

Conclusion

CSF awareness and usage among the students were 56.5 and 50.8%. Google drive is the most popular CSF. Lack of knowledge, accessibility, concerns on security and privacy limited CSF usage among students. Majority were interested to undergo training on CSF and undergraduate Information Communication Technology (ICT) curricula should introduce CSF as effective educational tools.
Integration of mental health care in private not-for-profit health centres in Guinea, West Africa: a systemic entry point towards the delivery of more patient-centred care?
Authors: Sow Abdoulaye , De Man Jeroen , De Spiegelaere Myriam , Vanlerberghe Veerle , Criel Bart
Published: January 2020

Background

Patient-centred care is an essential component of quality of health care. We hypothesize that integration of a mental health care package into versatile first-line health care services can strengthen patient participation, an important dimension of patient-centred care. The objective of this study is to analyse whether consultations conducted by providers in facilities that integrated mental health care score higher in terms of patient participation.

Methods

This study was conducted in Guinea in 12 not-for-profit health centres, 4 of which had integrated a mental health care package (MH+) and 8 had not (MH-). The study involved 450 general curative consultations (175 in MH+ and 275 in MH- centres), conducted by 18 care providers (7 in MH+ and 11 in MH- centres). Patients were interviewed after the consultation on how they perceived their involvement in the consultation, using the Patient Participation Scale (PPS). The providers completed a self-administered questionnaire on their perception of patient’s involvement in the consultation. We compared scores of the PPS between MH+ and MH- facilities and between patients and providers.

Results

The mean PPS score was 24.21 and 22.54 in MH+ and MH- health centres, respectively. Participation scores depended on both care providers and the health centres they work in. The patients consulting an MH+ centre were scoring higher on patient participation score than the ones of an MH- centre (adjusted odds ratio of 4.06 with a 95% CI of 1.17–14.10,p = 0.03). All care providers agreed they understood the patients’ concerns, and patients shared this view. All patients agreed they wanted to be involved in the decision-making concerning their treatment; providers, however, were reluctant to do so.

Conclusion

Integrating a mental health care package into versatile first-line health services can promote more patient-centred care.
Construction of a novel gene-based model for prognosis prediction of clear cell renal cell carcinoma
Authors: Zhang Zedan , Lin Enyu , Zhuang Hongkai , Xie Lu , Feng Xiaoqiang , Liu Jiumin , Yu Yuming
Published: January 2020

Background

Clear cell renal cell carcinoma (ccRCC) comprises the majority of kidney cancer death worldwide, whose incidence and mortality are not promising. Identifying ideal biomarkers to construct a more accurate prognostic model than conventional clinical parameters is crucial.

Methods

Raw count of RNA-sequencing data and clinicopathological data were acquired from The Cancer Genome Atlas (TCGA). Tumor samples were divided into two sets. Differentially expressed genes (DEGs) were screened in the whole set and prognosis-related genes were identified from the training set. Their common genes were used in LASSO and best subset regression which were performed to identify the best prognostic 5 genes. The gene-based risk score was developed based on the Cox coefficient of the individual gene. Time-dependent receiver operating characteristic (ROC) and Kaplan–Meier (KM) survival analysis were used to assess its prognostic power. GSE29609 dataset from GEO (Gene Expression Omnibus) database was used to validate the signature. Univariate and multivariate Cox regression were performed to screen independent prognostic parameters to construct a nomogram. The predictive power of the nomogram was revealed by time-dependent ROC curves and the calibration plot and verified in the validation set. Finally, Functional enrichment analysis of DEGs and 5 novel genes were performed to suggest the potential biological pathways.

Results

PADI1, ATP6V0D2, DPP6, C9orf135 and PLG were screened to be significantly related to the prognosis of ccRCC patients. The risk score effectively stratified the patients into high-risk group with poor overall survival (OS) based on survival analysis. AJCC-stage, age, recurrence and risk score were regarded as independent prognostic parameters by Cox regression analysis and were used to construct a nomogram. Time-dependent ROC curves showed the nomogram performed best in 1-, 3- and 5-year survival predictions compared with AJCC-stage and risk score in validation sets. The calibration plot showed good agreement of the nomogram between predicted and observed outcomes. Functional enrichment analysis suggested several enriched biological pathways related to cancer.

Conclusions

In our study, we constructed a gene-based model integrating clinical prognostic parameters to predict prognosis of ccRCC well, which might provide a reliable prognosis assessment tool for clinician and aid treatment decision-making in the clinic.
Prevalence of Plasmodium falciparum field isolates with deletions in histidine-rich protein 2 and 3 genes in context with sub-Saharan Africa and India: a systematic review and meta-analysis
Authors: Kojom Loick P. , Singh Vineeta
Published: January 2020

Background

In 2017, nearly 80% of malaria morbidity and mortality occurred in sub-Saharan African (SSA) countries and India. Rapid diagnostic tests (RDTs), especially those targeting histidine-rich protein 2 (PfHRP2) of Plasmodium falciparum, have become an important diagnostic tool in these malaria-endemic areas. However, the chances of RDT-oriented successful treatment are increasingly jeopardized by the appearance of mutants with deletions in pfhrp2 and pfhrp3 genes. This systematic review and meta-analysis determines the prevalence of field P. falciparum isolates with deletion in pfhrp2 and/or pfhrp3 genes and their proportion among false-negative results in the PfHRP2-based RDTs in SSA and India.

Methods

Eight electronic databases were used for searching potentially relevant publications for the systematic review analysis, wherein the main methodological aspects of included studies were analysed and some missing links in the included studies were identified.

Results

A total of 19 studies were included, 16 from SSA and 3 from India. The pooled prevalence of pfhrp2 deletions was 8 and 5% while 16 and 4% for pfhrp3 gene deletions in Africa and India, respectively. The pooled proportion of pfhrp2 gene deletions found among false negative PfHRP2-based RDTs results was about 27.0 and 69.0% in Africa and India, respectively.

Conclusions

This review study indicates a relatively high proportion of both pfhrp2/3 genes deletions in P. falciparum isolates and among false-negative malaria cases using PfHRP2-based RDT results in SSA and India. Recently the deletions in pfhrp2/3 genes have also been reported from two African countries (Nigeria and Sudan). This review emphasizes the importance of more extensive studies and standardization of studies addressing the pfhrp2/3 gene deletions in malarious areas.
Falciparum malaria from coastal Tanzania and Zanzibar remains highly connected despite effective control efforts on the archipelago
Authors: Morgan Andrew P. , Brazeau Nicholas F. , Ngasala Billy , Mhamilawa Lwidiko E. , Denton Madeline , Msellem Mwinyi , Morris Ulrika , Filer Dayne L. , Aydemir Ozkan , Bailey Jeffrey A. , Parr Jonathan B. , Mårtensson Andreas , Bjorkman Anders , Juliano Jonathan J.
Published: January 2020

Background

Tanzania’s Zanzibar archipelago has made significant gains in malaria control over the last decade and is a target for malaria elimination. Despite consistent implementation of effective tools since 2002, elimination has not been achieved. Importation of parasites from outside of the archipelago is thought to be an important cause of malaria’s persistence, but this paradigm has not been studied using modern genetic tools.

Methods

Whole-genome sequencing (WGS) was used to investigate the impact of importation, employing population genetic analyses of Plasmodium falciparum isolates from both the archipelago and mainland Tanzania. Ancestry, levels of genetic diversity and differentiation, patterns of relatedness, and patterns of selection between these two populations were assessed by leveraging recent advances in deconvolution of genomes from polyclonal malaria infections.

Results

Significant decreases in the effective population sizes were inferred in both populations that coincide with a period of decreasing malaria transmission in Tanzania. Identity by descent analysis showed that parasites in the two populations shared long segments of their genomes, on the order of 5 cM, suggesting shared ancestry within the last 10 generations. Even with limited sampling, two of isolates between the mainland and Zanzibar were identified that are related at the expected level of half-siblings, consistent with recent importation.

Conclusions

These findings suggest that importation plays an important role for malaria incidence on Zanzibar and demonstrate the value of genomic approaches for identifying corridors of parasite movement to the island.
Establishment of the circadian metabolic phenotype strategy in spontaneously hypertensive rats: a dynamic metabolomics study
Authors: Wang Huanjun , Wang Xiaoming , Qi Dongmei , Sun Mengjia , Hou Qingqing , Li Yunlun , Jiang Haiqiang
Published: January 2020

Background

Circadian rhythms play a fundamental role in the progression of cardiovascular events. Almost all cardiovascular diseases have a circadian misalignment usually characterized by changes in metabolites. This study aimed to dynamically monitor rhythmic biomarkers, to elucidate the metabolic pathways that are potentially under circadian control in spontaneously hypertensive rats (SHRs), and to eventually establish a circadian metabolic phenotype strategy based on metabolomics.

Methods

In this study, an untargeted metabolomics technology was used to dynamically monitor changes in serum metabolites between SHR model group and WKY control group. Liquid chromatography-mass spectrometry (LC–MS) combined with multivariate statistical analysis was applied to identify markers of hypertension rhythm imbalance. The concentrations of amino acids and their metabolites identified as markers were quantified by a subsequent targeted metabolomics analysis. Overall, these approaches comprehensively explored the rhythm mechanism and established a circadian metabolic phenotype strategy.

Results

The metabolic profile revealed a disorder in the diurnal metabolism pattern in SHRs. Moreover, multivariate statistical analysis revealed metabolic markers of rhythm homeostasis, such as arginine, proline, phenylalanine, citric acid,l-malic acid, succinic acid, etc., accompanied by an imbalance in hypertension. The key metabolic pathways related to rhythm imbalance in hypertension were found by enrichment analysis, including amino acid metabolism, and the tricarboxylic acid cycle (TCA). In addition, the quantitative analysis of amino acids and their metabolites showed that the changes in leucine, isoleucine, valine, taurine, serine, and glycine were the most obvious.

Conclusions

In summary, this study illustrated the relationship between metabolites and the pathways across time on hypertension. These results may provide a theoretical basis for personalized treatment programmes and timing for hypertension.
Automatic versus manual tuning of robot-assisted gait training in people with neurological disorders
Authors: Fricke Simone S. , Bayón Cristina , der Kooij Herman van , F. van Asseldonk Edwin H.
Published: January 2020

Background

In clinical practice, therapists choose the amount of assistance for robot-assisted training. This can result in outcomes that are influenced by subjective decisions and tuning of training parameters can be time-consuming. Therefore, various algorithms to automatically tune the assistance have been developed. However, the assistance applied by these algorithms has not been directly compared to manually-tuned assistance yet. In this study, we focused on subtask-based assistance and compared automatically-tuned (AT) robotic assistance with manually-tuned (MT) robotic assistance.

Methods

Ten people with neurological disorders (six stroke, four spinal cord injury) walked in the LOPES II gait trainer with AT and MT assistance. In both cases, assistance was adjusted separately for various subtasks of walking (in this study defined as control of: weight shift, lateral foot placement, trailing and leading limb angle, prepositioning, stability during stance, foot clearance). For the MT approach, robotic assistance was tuned by an experienced therapist and for the AT approach an algorithm that adjusted the assistance based on performances for the different subtasks was used. Time needed to tune the assistance, assistance levels and deviations from reference trajectories were compared between both approaches. In addition, participants evaluated safety, comfort, effect and amount of assistance for the AT and MT approach.

Results

For the AT algorithm, stable assistance levels were reached quicker than for the MT approach. Considerable differences in the assistance per subtask provided by the two approaches were found. The amount of assistance was more often higher for the MT approach than for the AT approach. Despite this, the largest deviations from the reference trajectories were found for the MT algorithm. Participants did not clearly prefer one approach over the other regarding safety, comfort, effect and amount of assistance.

Conclusion

Automatic tuning had the following advantages compared to manual tuning: quicker tuning of the assistance, lower assistance levels, separate tuning of each subtask and good performance for all subtasks. Future clinical trials need to show whether these apparent advantages result in better clinical outcomes.
Use and management of wild fauna by people of the Tehuacán-Cuicatlán Valley and surrounding areas, Mexico
Authors: Zarazúa-Carbajal Mariana , Chávez-Gutiérrez Michelle , Romero-Bautista Yessica , Rangel-Landa Selene , Moreno-Calles Ana Isabel , Ramos Luis Fernando Alvarado , Smith Sandra E. , Blancas José , del Val Ek , del Coro Arizmendi María , Casas Alejandro
Published: January 2020

Background

Interactions between humans and fauna lay in the heart of the history of human subsistence. In Mesoamerica, the Tehuacán-Cuicatlán Valley (TCV) harbours a high biodiversity with archaeological and ethnoecological evidence of its use by people inhabiting the area since at least 12,000 B.P. It is recognized as one of the most ancient areas of agriculture in the Americas, and a broad spectrum of management practices aimed to ensure the availability of desirable plants has been documented, but it has not been analysed for animals. This study aimed to investigate the use and management practices directed to wild animals along current settlements within the TCV and neighbouring areas.

Methods

We conducted an extensive search, review and analysis of documental sources for the period between 1967 and 2018. We found 38 documents providing information about the presence of animal species and 15 describing their use and/or management. We included our own observations from four case studies among the Ixcatec, Cuicatec, Nahua and Mestizo people, as well as from regional studies of biodiversity. We used unconstrained multivariate data analysis to describe the management typology of the animals in the region.

Results

Hitherto, 652 vertebrate species and 765 species of insects have been recorded in this area; and until present, 107 wild animal species have been reported to be used in 11 use-type categories, mostly for food (65.42%), ornamental (27.52%) and medicinal (21.10%) purposes by the Nahua, Cuicatec, Popolocan, Ixcatec, Mazatec and Mestizo people. Their extraction entails manual capture and gathering as well as hunting and trapping strategies, some of them involving planning in time or space and communitarian regulations; in addition, relocation actions and care in captivity were recorded. Nearly 178 of the species distributed in the region with no reports of local use are used in other localities of Mesoamerica. Ethnozoological information is still lacking for the Mixtec, Chinantec and Chocholtec people in the area.

Conclusions

Wild fauna is still a valuable resource for the inhabitants of the TCV. Animals are obtained through extractive practices, which vary from one another in their qualitative attributes. With this work, we provide a context for further research priorities on fauna management in a region of high biocultural significance.
Variability in usual care fluid resuscitation and risk-adjusted outcomes for mechanically ventilated patients in shock
Authors: Mansoori Jason N. , Linde-Zwirble Walter , Hou Peter C. , Havranek Edward P. , Douglas Ivor S.
Published: January 2020

Rationale

There remains significant controversy regarding the optimal approach to fluid resuscitation for patients in shock. The magnitude of care variability in shock resuscitation, the confounding effects of disease severity and comorbidity, and the relative impact on sepsis survival are poorly understood.

Objective

To evaluate usual care variability and determine the differential effect of observed and predicted fluid resuscitation volumes on risk-adjusted hospital mortality for mechanically ventilated patients in shock.

Methods

We performed a retrospective outcome analysis of mechanically ventilated patients admitted to intensive care units using the 2013 Premier Hospital Database (Premier, Inc.). Observed and predicted hospital mortality were evaluated by observed and predicted day 1 fluid administration, using the difference in predicted and observed outcomes to adjust for disease severity between groups. Both predictive models were validated using a second large administrative database (Truven Health Analytics Inc.). Secondary outcomes included duration of mechanical ventilation, hospital and ICU length of stay, and cost.

Results

Among 33,831 patients, observed hospital mortality was incrementally higher than predicted for each additional liter of day 1 fluid beginning at 7 L (40.9% vs. 37.2%, p = 0.008). Compared to patients that received expected (± 1.5 L predicted) day 1 fluid volumes, greater-than-expected fluid resuscitation was associated with increased risk-adjusted hospital mortality (52.3% vs. 45.0%, p < 0.0001) among all patients with shock and among a subgroup of shock patients with comorbid conditions predictive of lower fluid volume administration (47.1% vs. 41.5%, p < 0.0001). However, in patients with shock but without such conditions, both greater-than-expected (57.5% vs. 49.2%, p < 0.0001) and less-than-expected (52.1% vs. 49.2%, p = 0.037) day 1 fluid resuscitation were associated with increased risk-adjusted hospital mortality.

Conclusions

Highly variable day 1 fluid resuscitation was associated with a non-uniform impact on risk-adjusted hospital mortality among distinct subgroups of mechanically ventilated patients with shock. These findings support closer evaluation of fluid resuscitation strategies that include broadly applied fluid volume targets in the early phase of shock resuscitation.
Serum exosomal-annexin A2 is associated with African-American triple-negative breast cancer and promotes angiogenesis
Authors: Chaudhary Pankaj , Gibbs Lee D. , Maji Sayantan , Lewis Cheryl M. , Suzuki Sumihiro , Vishwanatha Jamboor K.
Published: January 2020

Background

Limited information is available on biomarker(s) for triple-negative breast cancer (TNBC) that can address the higher incidence and aggressiveness of TNBC in African-American (AA) women. Our previous studies have demonstrated annexin A2 (AnxA2) association with exosomes which promotes angiogenesis and metastasis. Therefore, our goal was to examine the expression and function of exosomal-annexin A2 (exo-AnxA2) derived from the serum samples of breast cancer patients.

Methods

The expression of serum exo-AnxA2 and its association with clinicopathological features of the breast cancer patients were determined. The role of serum exo-AnxA2 to promote angiogenesis was determined by an in vivo Matrigel plug assay.

Results

Our results show that the expression of serum exo-AnxA2 in breast cancer patients (n = 169; 83.33 ± 2.040 ng/mL, P < 0.0001) is high compared to non-cancer females (n = 68; 34.21 ± 2.238 ng/mL). High expression of exo-AnxA2 levels in breast cancer was significantly associated with tumor grade (P < 0.0001), poor overall survival (hazard ratio (HR) 2.802; 95% confidence intervals (CI) = 1.030–7.620; P = 0.0353), and poor disease-free survival (HR 7.934; 95% CI = 1.778–35.398; P = 0.0301). The expression of serum exo-AnxA2 levels was significantly elevated in TNBC (n = 68; 109.1 ± 2.905 ng/mL; P < 0.0001) in comparison to ER+ (n = 50; 57.35 ± 1.545 ng/mL), HER2+ (n = 59; 78.25 ± 1.146 ng/mL), and non-cancer females (n = 68; 34.21 ± 2.238 ng/mL). Exo-AnxA2 showed diagnostic values with a maximum AUC as 1.000 for TNBC, 0.8304 for ER+, and 0.9958 for HER2+ compared to non-cancer females. The expression of serum exo-AnxA2 was significantly elevated in AA women with TNBC (n = 29; 118.9 ± 4.086 ng/mL, P < 0.0001) in comparison to Caucasian-American TNBC (n = 27; 97.60 ± 3.298 ng/mL) patients. Our in vivo results suggest a role of serum exo-AnxA2 in angiogenesis and its association with aggressiveness of TNBC in AA women.

Conclusions

Our results demonstrated that the expression of serum exo-AnxA2 is high in AA women with TNBC and promotes angiogenesis. These findings suggest that exo-AnxA2 holds promise as a potential prognosticator of TNBC and may lead to an effective therapeutic option.