bluuebunny/crossref_metadata_2025 huggingface dataset:
Elucidation of trophic interactions in an unusual single-cell nitrogen-fixing symbiosis using metabolic modeling
Authors: Sarkar Debolina , Landa Marine , Bandyopadhyay Anindita , Pakrasi Himadri B. , Zehr Jonathan P. , Maranas Costas D.
Published: May 2021

Marine nitrogen-fixing microorganisms are an important source of fixed nitrogen in oceanic ecosystems. The colonial cyanobacterium Trichodesmium and diatom symbionts were thought to be the primary contributors to oceanic N2 fixation until the discovery of the unusual uncultivated symbiotic cyanobacterium UCYN-A (Candidatus Atelocyanobacterium thalassa). UCYN-A has atypical metabolic characteristics lacking the oxygen-evolving photosystem II, the tricarboxylic acid cycle, the carbon-fixation enzyme RuBisCo and de novo biosynthetic pathways for a number of amino acids and nucleotides. Therefore, it is obligately symbiotic with its single-celled haptophyte algal host. UCYN-A receives fixed carbon from its host and returns fixed nitrogen, but further insights into this symbiosis are precluded by both UCYN-A and its host being uncultured. In order to investigate how this syntrophy is coordinated, we reconstructed bottom-up genome-scale metabolic models of UCYN-A and its algal partner to explore possible trophic scenarios, focusing on nitrogen fixation and biomass synthesis. Since both partners are uncultivated and only the genome sequence of UCYN-A is available, we used the phylogenetically related Chrysochromulina tobin as a proxy for the host. Through the use of flux balance analysis (FBA), we determined the minimal set of metabolites and biochemical functions that must be shared between the two organisms to ensure viability and growth. We quantitatively investigated the metabolic characteristics that facilitate daytime N2 fixation in UCYN-A and possible oxygen-scavenging mechanisms needed to create an anaerobic environment to allow nitrogenase to function. This is the first application of an FBA framework to examine the tight metabolic coupling between uncultivated microbes in marine symbiotic communities and provides a roadmap for future efforts focusing on such specialized systems.
Misuse, perceived risk, and safety issues of household insecticides: Qualitative findings from focus groups in Arequipa, Peru
Authors: Larson Anika J. , Paz-Soldán Valerie A. , Arevalo-Nieto Claudia , Brown Joanna , Condori-Pino Carlos , Levy Michael Z. , Castillo-Neyra Ricardo
Published: May 2021

Background

The current body of research on insecticide use in Peru deals primarily with application of insecticides offered through Ministry of Health-led campaigns against vector-borne disease. However, there is a gap in the literature regarding the individual use, choice and perceptions of insecticides which may influence uptake of public health-based vector control initiatives and contribute to the thousands of deaths annually from acute pesticide poisoning in Peru.

Methods

Residents (n = 49) of the Alto Selva Alegre and CC districts of peri-urban Arequipa participated in seven focus group discussions (FGD). Using a FGD guide, two facilitators led the discussion and conducted a role-playing activity. this activity, participants insecticides (represented by printed photos of insecticides available locally) and pretended to “sell” the insecticides to other participants, including describing their qualities as though they were advertising the insecticide. The exercise was designed to elicit perceptions of currently available insecticides. The focus groups also included questions about participants’ preferences, use and experiences related to insecticides outside the context of this activity. Focus group content was transcribed, and qualitative data were analyzed with Atlas.ti and coded using an inductive process to generate major themes related to use and choice of insecticides, and perceived risks associated with insecticide use.

Results

The perceived risks associated with insecticides included both short- and long-term health impacts, and safety for children emerged as a priority. However, in some cases insecticides were reportedly applied in high-risk ways including application of insecticides directly to children and bedding. Some participants attempted to reduce the risk of insecticide use with informal, potentially ineffective personal protective equipment and by timing application when household members were away. Valued insecticide characteristics, such as strength and effectiveness, were often associated with negative characteristics such as odor and health impacts. “Agropecuarios” (agricultural supply stores) were considered a trusted source of information about insecticides and their health risks.

Conclusions

It is crucial to characterize misuse and perceptions of health impacts and risks of insecticides at the local level, as well as to find common themes and patterns across populations to inform national and regional programs to prevent acute insecticide poisoning and increase community participation in insecticide-based vector control campaigns. We detected risky practices and beliefs about personal protective equipment, risk indicators, and safety levels that could inform such preventive campaigns, as well as trusted information sources such as agricultural stores for partnerships in disseminating information.
Latent class regression improves the predictive acuity and clinical utility of survival prognostication amongst chronic heart failure patients
Authors: Mbotwa John L. , Kamps Marc de , Baxter Paul D. , Ellison George T. H. , Gilthorpe Mark S.
Published: May 2021

The present study aimed to compare the predictive acuity of latent class regression (LCR) modelling with: standard generalised linear modelling (GLM); and GLMs that include the membership of subgroups/classes (identified through prior latent class analysis; LCA) as alternative or additional candidate predictors. Using real world demographic and clinical data from 1,802 heart failure patients enrolled in the UK-HEART2 cohort, the study found that univariable GLMs using LCA-generated subgroup/class membership as the sole candidate predictor of survival were inferior to standard multivariable GLMs using the same four covariates as those used in the LCA. The inclusion of the LCA subgroup/class membership together with these four covariates as candidate predictors in a multivariable GLM showed no improvement in predictive acuity. In contrast, LCR modelling resulted in a 18–22% improvement in predictive acuity and provided a range of alternative models from which it would be possible to balance predictive acuity against entropy to select models that were optimally suited to improve the efficient allocation of clinical resources to address the differential risk of the outcome (in this instance, survival). These findings provide proof-of-principle that LCR modelling can improve the predictive acuity of GLMs and enhance the clinical utility of their predictions. These improvements warrant further attention and exploration, including the use of alternative techniques (including machine learning algorithms) that are also capable of generating latent class structure while determining outcome predictions, particularly for use with large and routinely collected clinical datasets, and with binary, count and continuous variables.
Intention to use institutional delivery service and its predictors among pregnant women, North West Ethiopia: Using theory of planned behavior
Authors: Ayana Abirham , Kassie Ayenew , Azale Telake
Published: May 2021

Background

Improving institutional delivery service is the most crucial strategies to reduce maternal and neonatal mortalities. In developing countries, only 50% of pregnant women deliver in health facilities and in Ethiopia only 48% of pregnant women deliver in health facilities. Maternal mortality remains the highest in Ethiopia. This study assessed intention to use institutional delivery service and its predictors among pregnant women using theory of planned behavior.

Methods

Community-based cross-sectional study was conducted among 645 Yilmana Densa District Pregnant women using multi-stage followed by cluster sampling technique. Data were entered into Epi Data version 4.6.0.2 and analyzed with STATA version 14. Binary logistic regression analysis was done to identify independent predictors of intention at 95% confidence level and P < 0.05 was used to determine statistically significant predictors.

Results

Intention of pregnant women to use institutional delivery service was 74.3% (CI; 70.71%, 77.6%). In the multivariable logistic regression; those who had 1–3 and 4 &above antenatal care 2.85(1.41, 5.75) and 3.14(1.16, 8.45) respectively, those who had past experience of institutional delivery (AOR = 3.39, 95%CI: 1.72, 6.71), parity of 1–3 and 4 & above % (AOR = 0.37, 0.19, 0.71) and (AOR = 0.25, 95%CI: 0.12, 0.55) respectively, rural residence (AOR = 0.51, 95%CI: 0.27, 0.96), favorable attitude (AOR = 2.93, 95%CI: 1.56, 5.50), favorable perceived behavioral control (AOR = 2.60, 95%CI: 1.44, 4.69) were factors significantly associated with intention to use institutional delivery service.

Conclusion and recommendation

Majority of the pregnant women were intended to deliver in the institution. Good Knowledge on institutional delivery, antenatal care visit, past experience of institutional delivery, rural residence, parity, attitude and perceived behavioral control were identified factors significantly associated with intention to use institutional delivery service. So, strengthening awareness creation and behavioral change communication programs are required at all levels of health system to raise intention of residents towards institutional delivery.
Umbilical cord miRNAs to predict neonatal early onset sepsis
Authors: Ernst Linda M. , Mithal Leena B. , Mestan Karen , Wang Vivien , Mangold Kathy A. , Freedman Alexa , Das Sanchita
Published: May 2021

Objective

To determine if miRNA (miR) expression in umbilical cord blood and umbilical cord tissue differs between neonates with early onset sepsis (EOS) versus neonates without true infection.

Methods

Retrospective case-control study design of human patients with EOS (n = 8), presumed sepsis (N = 12) and non-infected control patients (N = 21). Differential expression of >300 miRs was examined using the MIHS-3001ZE-miScript miRNA PCR Array Human miFinder 384HC. Expression levels of miRs were normalized using the global Ct mean of expressed miR and compared between groups. Data analysis was performed using GeneGlobe data analysis software. Ratios of over and under-expressed miRs were calculated and compared between groups using receiver operating characteristic (ROC) curves.

Results

Both umbilical cord plasma and umbilical cord tissue revealed several miRs with differential expression with little overlap between the two specimen types. The most overexpressed miR in plasma of EOS patients was miR-211-5p and the most overexpressed in EOS cord tissue was miR-223-5p. ROC curves comparing the ratios of over and under-expressed miRs for EOS patients and controls resulted in an area under the curve of 0.787 for cord plasma (miR-211-5p/miR-142-3p) and 0.988 for umbilical cord tissue (miR-223-5p/miR-22-3p), indicating good discrimination.

Conclusions

miRs show differential expression in EOS versus non-infected controls and presumed sepsis. A ratio of over and under-expressed miRs can provide a potentially sensitive and specific diagnostic test for EOS.
Genome-wide DNA methylation and RNA-seq analyses identify genes and pathways associated with doxorubicin resistance in a canine diffuse large B-cell lymphoma cell line
Authors: Hsu Chia-Hsin , Tomiyasu Hirotaka , Liao Chi-Hsun , Lin Chen-Si
Published: May 2021

Doxorubicin resistance is a major challenge in the successful treatment of canine diffuse large B-cell lymphoma (cDLBCL). In the present study, MethylCap-seq and RNA-seq were performed to characterize the genome-wide DNA methylation and differential gene expression patterns respectively in CLBL-1 8.0, a doxorubicin-resistant cDLBCL cell line, and in CLBL-1 as control, to investigate the underlying mechanisms of doxorubicin resistance in cDLBCL. A total of 20289 hypermethylated differentially methylated regions (DMRs) were detected. Among these, 1339 hypermethylated DMRs were in promoter regions, of which 24 genes showed an inverse correlation between methylation and gene expression. These 24 genes were involved in cell migration, according to gene ontology (GO) analysis. Also, 12855 hypermethylated DMRs were in gene-body regions. Among these, 353 genes showed a positive correlation between methylation and gene expression. Functional analysis of these 353 genes highlighted that TGF-β and lysosome-mediated signal pathways are significantly associated with the drug resistance of CLBL-1. The tumorigenic role of TGF-β signaling pathway in CLBL-1 8.0 was further validated by treating the cells with a TGF-β inhibitor(s) to show the increased chemo-sensitivity and intracellular doxorubicin accumulation, as well as decreased p-glycoprotein expression. In summary, the present study performed an integrative analysis of DNA methylation and gene expression in CLBL-1 8.0 and CLBL-1. The candidate genes and pathways identified in this study hold potential promise for overcoming doxorubicin resistance in cDLBCL.
Increased risk of secondary lung cancer in patients with tuberculosis: A nationwide, population-based cohort study
Authors: Ho Li-Ju , Yang Hung-Yi , Chung Chi-Hsiang , Chang Wei-Chin , Yang Sung-Sen , Sun Chien-An , Chien Wu-Chien , Su Ruei-Yu
Published: May 2021

Background

Tuberculosis (TB) presents a global threat in the world and the lung is the frequent site of metastatic focus. A previous study demonstrated that TB might increase primary lung cancer risk by two-fold for more than 20 years after the TB diagnosis. However, no large-scale study has evaluated the risk of TB and secondary lung cancer. Thus, we evaluated the risk of secondary lung cancer in patients with or without tuberculosis (TB) using a nationwide population-based dataset.

Methods

In a cohort study of 1,936,512 individuals, we selected 6934 patients among patients with primary cancer and TB infection, based on the International Classification of Disease (ICD-p-CM) codes 010–011 from 2000 to 2015. The control cohort comprised 13,868 randomly selected, propensity-matched patients (by age, gender, and index date) without TB exposure. Using this adjusted date, a possible association between TB and the risk of developing secondary lung cancer was estimated using a Cox proportional hazards regression model.

Results

During the follow-up period, secondary lung cancer was diagnosed in 761 (10.97%) patients with TB and 1263 (9.11%) patients without TB. After adjusting for covariates, the risk of secondary lung cancer was 1.67 times greater among primary cancer in the cohort with TB than in the cohort without TB. Stratification revealed that every comorbidity (including diabetes, hypertension, cirrhosis, congestive heart failure, cardiovascular accident, chronic kidney disease, chronic obstructive pulmonary disease) significantly increased the risk of secondary lung cancer when comparing the TB cohort with the non-TB cohort. Moreover, the primary cancer types (including head and neck, colorectal cancer, soft tissue sarcoma, breast, kidney, and thyroid cancer) had a more significant risk of becoming secondary lung cancer.

Conclusion

A significant association exists between TB and the subsequent risk for metastasis among primary cancers and comorbidities. Therefore, TB patients should be evaluated for the subsequent risk of secondary lung cancer.
High frequency of potential phosphodiesterase type 5 inhibitor drug interactions in males with HIV infection and erectile dysfunction
Authors: Cota Jason M. , Benavides Taylor M. , Fields John D. , Jansen Nathan , Ganesan Anuradha , Colombo Rhonda E. , Blaylock Jason M. , Maves Ryan C. , Agan Brian K. , Okulicz Jason F.
Published: May 2021

Objectives

We sought to determine the prevalence of phosphodiesterase type 5 inhibitor (PDE-5) mediated drug-drug interactions (DDIs) in males with HIV infection receiving antiretroviral therapy (ART) and identify factors associated with PDE-5-mediated DDIs.

Methods

Male US Military HIV Natural History Study participants diagnosed with erectile dysfunction (ED) and having a PDE-5 inhibitor and potentially-interacting ART co-dispensed within 30 days were included. DDIs were defined according to criteria found in published guidelines and drug information resources. The primary outcome of interest was overall PDE-5 inhibitor-mediated DDI prevalence and episode duration. A secondary logistic regression analysis was performed on those with and without DDIs to identify factors associated with initial DDI episode.

Results

A total of 235 male participants with ED met inclusion criteria. The majority were White (50.6%) or African American (40.4%). Median age at medication co-dispensing (45 years), duration of HIV infection (14 years), and duration of ED (1 year) did not differ between the two groups (p>0.05 for all). PDE-5 inhibitors included sildenafil (n = 124), vardenafil (n = 99), and tadalafil (n = 14). ART regimens included RTV-boosted protease inhibitors (PIs) atazanavir (n = 83) or darunavir (n = 34), and COBI-boosted elvitegravir (n = 43). Potential DDIs occurred in 181 (77.0%) participants, of whom 122 (67.4%) had multiple DDI episodes. The median DDI duration was 8 (IQR 1–12) months. In multivariate analyses, non-statistically significant higher odds of DDIs were observed with RTV-boosted PIs or PI-based ART (OR 2.13, 95% CI 0.85–5.37) and in those with a diagnosis of major depressive disorder (OR 1.74, 95% CI 0.83–3.64).

Conclusions

PDE-5-mediated DDIs were observed in the majority of males with HIV infection on RTV- or COBI-boosted ART in our cohort. This study highlights the importance of assessing for DDIs among individuals on ART, especially those on boosted regimens.
Assessing private provider perceptions and the acceptability of video observed treatment technology for tuberculosis treatment adherence in three cities across Viet Nam
Authors: Nguyen Lan Huu , Tran Phuong Thi Minh , Dam Thu Anh , Forse Rachel Jeanette , Codlin Andrew James , Huynh Huy Ba , Dong Thuy Thi Thu , Nguyen Giang Hoai , Truong Vinh Van , Dang Ha Thi Minh , Nguyen Tuan Dinh , Nguyen Hoa Binh , Nguyen Nhung Viet , Khan Amera , Creswell Jacob , Vo Luan Nguyen Quang
Published: May 2021

Background

The World Health Organization recently recommended Video Observed Therapy (VOT) as one option for monitoring tuberculosis (TB) treatment adherence. There is evidence that private sector TB treatment has substandard treatment follow-up, which could be improved using VOT. However, acceptability of VOT in the private sector has not yet been evaluated.

Methods

We conducted a cross-sectional survey employing a theoretical framework for healthcare intervention acceptability to measure private provider perceptions of VOT across seven constructs in three cities of Viet Nam: Ha Noi, Ho Chi Minh City, and Hai Phong. We investigated the differences in private providers’ attitudes and perceptions of VOT using mixed ordinal models to test for significant differences in responses between groups of providers stratified by their willingness to use VOT.

Results

A total of 79 private providers completed the survey. Sixty-two providers (75%) indicated they would use VOT if given the opportunity. Between private providers who would and would not use VOT, there were statistically significant differences (p≤0.001) in the providers’ beliefs that VOT would help identify side effects faster and in their confidence to monitor treatment and provide differentiated care with VOT. There were also significant differences in providers’ beliefs that VOT would save them time and money, address problems faced by their patients, benefit their practice and patients, and be relevant for all their patients.

Conclusion

Private providers who completed the survey have positive views towards using VOT and specific subpopulations acknowledge the value of integrating VOT into their practice. Future VOT implementation in the private sector should focus on emphasizing the benefits and relevance of VOT during recruitment and provide programmatic support for implementing differentiated care with the technology.
Predictive performance of oximetry in detecting sleep apnea in surgical patients with cardiovascular risk factors
Authors: Waseem Rida , Chan Matthew T. V. , Wang Chew Yin , Seet Edwin , Chung Frances
Published: May 2021

Introduction

In adults with cardiovascular risk factors undergoing major noncardiac surgery, unrecognized obstructive sleep apnea (OSA) was associated with postoperative cardiovascular complications. There is a need for an easy and accessible home device in predicting sleep apnea. The objective of the study is to determine the predictive performance of the overnight pulse oximetry in predicting OSA in at-risk surgical patients.

Methods

This was a planned post-hoc analysis of multicenter prospective cohort study involving 1,218 at-risk surgical patients without prior diagnosis of sleep apnea. All patients underwent home sleep apnea testing (ApneaLink Plus, ResMed) simultaneously with pulse oximetry (PULSOX-300i, Konica Minolta Sensing, Inc). The predictive performance of the 4% oxygen desaturation index (ODI) versus apnea-hypopnea index (AHI) were determined.

Results

Of 1,218 patients, the mean age was 67.2 ± 9.2 years and body mass index (BMI) was 27.0 ± 5.3 kg/m2. The optimal cut-off for predicting moderate-to-severe and severe OSA was ODI ≥15 events/hour. For predicting moderate-to-severe OSA (AHI ≥15), the sensitivity and specificity of ODI ≥ 15 events per hour were 88.4% (95% confidence interval [CI], 85.7–90.6) and 95.4% (95% CI, 94.2–96.4). For severe OSA (AHI ≥30), the sensitivity and specificity were 97.2% (95% CI, 92.7–99.1) and 78.8% (95% CI, 78.2–79.0). The area under the curve (AUC) for moderate-to-severe and severe OSA was 0.983 (95% CI, 0.977–0.988) and 0.979 (95% CI, 0.97–0.909) respectively.

Discussion

ODI from oximetry is sensitive and specific in predicting moderate-to-severe or severe OSA in at-risk surgical population. It provides an easy, accurate, and accessible tool for at-risk surgical patients with suspected OSA.
Welfare impacts of smallholder farmers’ participation in multiple output markets: Empirical evidence from Tanzania
Authors: Manda Julius , Azzarri Carlo , Feleke Shiferaw , Kotu Bekele , Claessens Lieven , Bekunda Mateete
Published: May 2021

A relatively large body of literature has documented the welfare effects of smallholder farmers’ participation in single-commodity output markets. However, limited empirical evidence is available when smallholder farmers participate in multiple-commodities output markets. We tried to fill this gap in the literature by estimating the impacts of smallholder farmers’ contemporaneous participation in both maize and legume markets vis-à-vis in only maize or legume markets using household-level data from Tanzania. Applying a multinomial endogenous switching regression model that allows controlling for observed and unobserved heterogeneity associated with market participation in single-commodity and multiple-commodity markets, results showed that smallholder farmers’ participation in both single–and multiple–commodity markets was positively and significantly associated with household income and food security. Moreover, the greatest benefits were obtained when farmers participated in multiple-commodity markets, suggesting the importance of policies promoting diversification in crop income sources to increase welfare and food security. Our findings also signal the complementary–rather than substitute–nature of accessing multiple-commodity markets for enhancing household livelihoods under a specialization strategy. Finally, important policy implications are suggested, from promoting and supporting public infrastructure investments to expanding road networks to reduce transportation costs, especially in remote communities, to enhance smallholder farmer access to profitable maize and legume markets in Tanzania.
Age and remission induction therapy for acute myeloid leukemia: An analysis of data from the Korean acute myeloid leukemia registry
Authors: Yoo Kwai Han , Kim Hyeoung-Joon , Min Yoo Hong , Hong Dae-Sik , Lee Won Sik , Kim Hee-Je , Shin Ho-Jin , Park Yong , Lee Je-Hwan , Kim Hawk
Published: May 2021

Objective

The clinical characteristics and therapeutic strategy in acute myeloid leukemia (AML) are influenced by patients’ age. We evaluated the impact of age on remission induction therapy for AML.

Methods

We retrospectively analyzed 3,011 adult AML patients identified from a nationwide database between January 2007 and December 2011.

Results

Three hundred twenty-nine (10.9%) acute promyelocytic leukemia (APL) and 2,682 (89.1%) non-APL patients were analyzed. The median age was 51 years and 55% of patients were male. Six hundred twenty-three patients (21%) were at favorable risk, 1522 (51%) were at intermediate risk, and 743 (25%) were at poor risk. As the age increased, the proportion of those at favorable risk and who received induction chemotherapy decreased. After induction therapy, complete response (CR) was achieved in 81.5% (243/298) of APL and 62.4% (1,409/2,258) of non-APL patients; these rates decreased as the age increased, with an obvious decrement in those older than 60 years. The median overall survival of non-APL patients was 18.7 months, while that of APL patients was not reached, with a 75% five-year survival rate.

Conclusions

Age impacts both the biology and clinical outcomes of AML patients. Further studies should confirm the role of induction remission chemotherapy by age group.
Evaluation of a marker independent isolation method for circulating tumor cells in esophageal adenocarcinoma
Authors: Philippron Annouck , Depypere Lieven , Oeyen Steffi , De Laere Bram , Vandeputte Charlotte , Nafteux Philippe , De Preter Katleen , Pattyn Piet
Published: May 2021

Objective

The enrichment of circulating tumor cells (CTCs) from blood provides a minimally invasive method for biomarker discovery in cancer. Longitudinal interrogation allows monitoring or prediction of therapy response, detection of minimal residual disease or progression, and determination of prognosis. Despite inherent phenotypic heterogeneity and differences in cell surface marker expression, most CTC isolation technologies typically use positive selection. This necessitates the optimization of marker-independent CTC methods, enabling the capture of heterogenous CTCs. The aim of this report is to compare a size-dependent and a marker-dependent CTC-isolation method, using spiked esophageal cells in healthy donor blood and blood from patients diagnosed with esophageal adenocarcinoma.

Methods

Using esophageal cancer cell lines (OE19 and OE33) spiked into blood of a healthy donor, we investigated tumor cell isolation by Parsortix post cell fixation, immunostaining and transfer to a glass slide, and benchmarked its performance against the CellSearch system. Additionally, we performed DEPArray cell sorting to infer the feasibility to select and isolate cells of interest, aiming towards downstream single-cell molecular characterization in future studies. Finally, we measured CTC prevalence by Parsortix in venous blood samples from patients with various esophageal adenocarcinoma tumor stages.

Results

OE19 and OE33 cells were spiked in healthy donor blood and subsequently processed using CellSearch (n = 16) or Parsortix (n = 16). Upon tumor cell enrichment and enumeration, the recovery rate ranged from 76.3 ± 23.2% to 21.3 ± 9.2% for CellSearch and Parsortix, respectively. Parsortix-enriched and stained cell fractions were successfully transferred to the DEPArray instrument with preservation of cell morphology, allowing isolation of cells of interest. Finally, despite low CTC prevalence and abundance, Parsortix detected traditional CTCs (i.e. cytokeratin+/CD45-) in 8/29 (27.6%) of patients with esophageal adenocarcinoma, of whom 50% had early stage (I-II) disease.

Conclusions

We refined an epitope-independent isolation workflow to study CTCs in patients with esophageal adenocarcinoma. CTC recovery using Parsortix was substantially lower compared to CellSearch when focusing on the traditional CTC phenotype with CD45-negative and cytokeratin-positive staining characteristics. Future research could determine if this method allows downstream molecular interrogation of CTCs to infer new prognostic and predictive biomarkers on a single-cell level.
Assessment of body composition in spinal cord injury: A scoping review
Authors: van der Scheer Jan W. , Totosy de Zepetnek Julia O. , Blauwet Cheri , Brooke-Wavell Katherine , Graham-Paulson Terri , Leonard Amber N. , Webborn Nick , Goosey-Tolfrey Victoria L.
Published: May 2021

The objective of this scoping review was to map the evidence on measurement properties of body composition tools to assess whole-body and regional fat and fat-free mass in adults with SCI, and to identify research gaps in order to set future research priorities. Electronic databases of PubMed, EMBASE and the Cochrane library were searched up to April 2020. Included studies employed assessments related to whole-body or regional fat and/or fat-free mass and provided data to quantify measurement properties that involved adults with SCI. All searches and data extractions were conducted by two independent reviewers. The scoping review was designed and conducted together with an expert panel (n = 8) that represented research, clinical, nutritional and lived SCI experience. The panel collaboratively determined the scope and design of the review and interpreted its findings. Additionally, the expert panel reached out to their professional networks to gain further stakeholder feedback via interactive practitioner surveys and workshops with people with SCI. The research gaps identified by the review, together with discussions among the expert panel including consideration of the survey and workshop feedback, informed the formulation of future research priorities. A total of 42 eligible articles were identified (1,011 males and 143 females). The only tool supported by studies showing both acceptable test-retest reliability and convergent validity was whole-body dual-energy x-ray absorptiometry (DXA). The survey/workshop participants considered the measurement burden of DXA acceptable as long as it was reliable, valid and would do no harm (e.g. radiation, skin damage). Practitioners considered cost and accessibility of DXA major barriers in applied settings. The survey/workshop participants expressed a preference towards simple tools if they could be confident in their reliability and validity. This review suggests that future research should prioritize reliability and validity studies on: (1) DXA as a surrogate ‘gold standard’ tool to assess whole-body composition, regional fat and fat-free mass; and (2) skinfold thickness and waist circumference as practical low-cost tools to assess regional fat mass in persons with SCI, and (3) females to explore potential sex differences of body composition assessment tools.

Registration review protocol: CRD42018090187 (PROSPERO).
Discordant congenital heart defects in monochorionic twins: Risk factors and proposed pathophysiology
Authors: Imany-Shakibai Helia , Yin Ophelia , Russell Matthew R. , Sklansky Mark , Satou Gary , Afshar Yalda
Published: May 2021

A six-fold increase in congenital heart defects (CHD) exists among monochorionic (MC) twins compared to singleton or dichorionic twin pregnancies. Though MC twins share an identical genotype, discordant phenotypes related to CHD and other malformations have been described, with reported rates of concordance for various congenital anomalies at less than 20%. Our objective was to characterize the frequency and spectrum of CHD in a contemporary cohort of MC twins, coupled with genetic and clinical variables to provide insight into risk factors and pathophysiology of discordant CHD in MC twins. Retrospective analysis of all twins receiving prenatal fetal echocardiography at a single institution from January 2010 –March 2020 (N = 163) yielded 23 MC twin pairs (46 neonates) with CHD (n = 5 concordant CHD, n = 18 discordant CHD). The most common lesions were septal defects (60% and 45.5% in concordant and discordant cohorts, respectively) and right heart lesions (40% and 18.2% in concordant and discordant cohorts, respectively). Diagnostic genetic testing was abnormal for 20% of the concordant and 5.6% of the discordant pairs, with no difference in rate of abnormal genetic results between the groups (p = 0.395). No significant association was found between clinical risk factors and development of discordant CHD (p>0.05). This data demonstrates the possibility of environmental and epigenetic influences versus genotypic factors in the development of discordant CHD in monochorionic twins.
CD200R1 and CD200R1L expression is regulated during B cell development in swine and modulates the Ig production in response to the TLR7 ligand imiquimoid
Authors: Poderoso Teresa , De la Riva Paloma Martínez , Álvarez Belén , Ezquerra Ángel , Domínguez Javier , Revilla Concepción
Published: May 2021

The CD200R family comprises a group of paired receptors that can modulate the activation of immune cells. They are expressed both on myeloid cells and lymphocyte subsets. Here we report that the expression of these receptors on porcine B cells is tightly regulated, being mainly expressed on mature cells. The expression of the inhibitory receptors CD200R1 and/or its splicing variant CD200R1X2, either in combination or not with the activating receptor CD200R1L, is upregulated in sIgM+ effector/memory cells, and tends to decline thereafter as these cells progress to plasmablasts or switch the Ig isotype. sIgM+ naïve and primed cells only express, by contrast, the CD200R1X2 receptor. B-1 like cells also express CD200R1 isoforms, either alone or in combination with CD200R1L. Treatment of peripheral blood mononuclear cells with a monoclonal antibody specific for inhibitory receptors, enhances the IgM and IgG production induced by TLR7 stimulation suggesting a modulatory role of B cell functions of these receptors.
Knowledge and beliefs about the use/abuse of oral contraceptive pills among males: A mixed-method explanatory sequential study in community pharmacy settings
Authors: Barakat Muna , Al-Qudah Raja’a , Akour Amal , Abu-Asal Mona , Thiab Samar , Dallal Bashi Yahya H.
Published: May 2021

Background

Oral contraceptive pills (OCPs) are considered one of the most important birth control methods globally. However, these pills were designed for female administration rather than males. This study was designed to investigate patterns of OCPs use and abuse among Jordanian males, according to the community pharmacists’ observations.

Method

A mixed-method explanatory sequential study was conducted using an online self-administered survey, followed by semi-structured in-depth interviews for registered pharmacists, assistant pharmacists and pharmacy interns. The interviews were utilized using a conceptual framework. Inductive thematic analysis and descriptive/regression analyses were completed using Nvivo and SPSS, respectively.

Results

A total of 158 questionnaire responses and 22 interviews were included in our analysis. Around half (48.4%) of the questionnaire responses confirmed that males could use OCPs for hair growth enhancement, muscle gain and acne treatment 12.7%, 31.7% and 4.4%, respectively. Through the interviews, the participating pharmacists highlighted that males use OCPs mostly for bodybuilding purposes, according to recommendations by their coaches at the gym. The most abused OCPs containing estrogen (Ethinyl estradiol) and progestins (Drospirenone or Levonorgestrel).

Conclusion

This study provided insight into unexpected uses of OCPs by males in Jordan. Community pharmacists have a crucial role in the management of OCPs use and abuse. However, restricted regulations and monitoring must be released and implemented on the community to limit such practices.
Pediatric high users of Canadian hospitals and emergency departments
Authors: Tiller Ryan , Chan Kevin , Knight John C. , Chafe Roger
Published: May 2021

Introduction

Few studies have examined the most frequent pediatric users of hospital services. Our objective was to determine the clinical diagnoses, demographic characteristics, and medical severity of high-use pediatric patients in Canada.

Methods

We conducted a retrospective analysis of patients <18 years of age who either were admitted to hospital or visited an emergency department (ED) using the Canadian Institute for Health Information’s (CIHI) Dynamic Cohort of Complex, High System Users. The analysis of hospital admission data excluded Quebec and Manitoba. ED data was only available for Alberta and Ontario.

Results

121 104 patients were identified as the most frequent hospital users and 459 998 patients as the most frequent ED users. High users were more likely to reside in a rural community, to be in a lower income quintile, and face more deprivation. The most frequent conditions for hospitalization for high use patients were disorders related to length of prematurity and fetal growth, respiratory and cardiovascular disorders specific to the perinatal period, and haemorrhagic and haematological disorders of fetus and newborn. For the most frequent ED users, the most common clinical diagnoses were acute upper respiratory infections, injuries to the head, and diseases of the middle ear and mastoid.

Conclusion

Pediatric high users by frequency of hospital and ED services are a distinct population. Better understanding their characteristics will allow for more appropriate planning of children’s health services and help identify areas for effective preventive or quality improvement initiatives.
Peripheral-neuron-like properties of differentiated human dental pulp stem cells (hDPSCs)
Authors: Arimura Yuki , Shindo Yutaka , Yamanaka Ryu , Mochizuki Mai , Hotta Kohji , Nakahara Taka , Ito Etsuro , Yoshioka Tohru , Oka Kotaro
Published: May 2021

Elucidating the mechanisms underlying human pain sensation requires the establishment of an in vitro model of pain reception comprising human cells expressing pain-sensing receptors and function properly as neurons. Human dental pulp stem cells (hDPSCs) are mesenchymal stem cells and a promising candidate for producing human neuronal cells, however, the functional properties of differentiated hDPSCs have not yet been fully characterized. In this study, we demonstrated neuronal differentiation of hDPSCs via both their expression of neuronal marker proteins and their neuronal function examined using Ca2+ imaging. Moreover, to confirm the ability of nociception, Ca2+ responses in differentiated hDPSCs were compared to those of rat dorsal root ganglion (DRG) neurons. Those cells showed similar responses to glutamate, ATP and agonists of transient receptor potential (TRP) channels. Since TRP channels are implicated in nociception, differentiated hDPSCs provide a useful in vitro model of human peripheral neuron response to stimuli interpreted as pain.
Direct health system costs for systemic lupus erythematosus patients in Alberta, Canada
Authors: Fatoye Francis , Gebrye Tadesse , Svenson Lawrence W.
Published: May 2021

Systemic lupus Erythematosus (SLE) is a chronic multi-system autoimmune disease that can affect a person’s physical, mental, and social life. It imposes a substantial economic burden up on patients, carers, healthcare systems, and wider society. This is the first study to examine the direct health care costs of SLE in Alberta using real-world data. Alberta maintains a publicly funded, universally available health care system. Health service use and direct healthcare costs of SLE and non-SLE cases were determined from inpatient hospital services, fee-for-physician services, emergency services, and ambulatory care services. All costs were estimated for calendar year 2016. Data were analysed using central measures specifically the mean to determine the annual costs of SLE and non-SLE. A total number of 10,932 (Male = 2,546; Female = 8,386), and 41,851,36 (Male = 21,157,76; Female = 20,693,60) of SLE and non-SLE cases, respectively were included in this study. The mean annual costs of SLE, and non-SLE per case were $7,740.19 (Male = $7,986.59; Female = $7,665.38), and $2,479.53 (Male = $2,265.57; Female = $2,698.30), (p < 0.001) respectively. The mean annual costs of fee-for-physician services (SLE = $2,160.03; non-SLE = $840.00) (p < 0.001), inpatient hospital services (SLE = $3,462.86; non-SLE = $1,007.29), (p < 0.001) emergency services (SLE = $440.28; non-SLE = $176.65), (p < 0.001) and ambulatory care services (SLE = $1,677.03; non-SLE = $455.05) (p < 0.001) per case were estimated. The findings showed that the costs of SLE were considerably high for patients and healthcare system. This highlights the importance of appropriate treatment and management of SLE. Further studies are required to fully investigate both the direct and indirect economic burden of SLE including out-of-pocket expenses, costs to patients and caregivers and productivity loss.
Pseudomonas aeruginosa–induced nociceptor activation increases susceptibility to infection
Authors: Lin Tiffany , Quellier Daisy , Lamb Jeffrey , Voisin Tiphaine , Baral Pankaj , Bock Felix , Schönberg Alfrun , Mirchev Rossen , Pier Gerald , Chiu Isaac , Gadjeva Mihaela
Published: May 2021

We report a rapid reduction in blink reflexes duringin vivoocularPseudomonas aeruginosainfection, which is commonly attributed and indicative of functional neuronal damage. Sensory neurons derivedin vitrofrom trigeminal ganglia (TG) were able to directly respond toP.aeruginosabut reacted significantly less to strains ofP.aeruginosathat lacked virulence factors such as pili, flagella, or a type III secretion system. These observations led us to explore the impact of neurons on the host’s susceptibility toP.aeruginosakeratitis. Mice were treated with Resiniferatoxin (RTX), a potent activator of Transient Receptor Potential Vanilloid 1 (TRPV1) channels, which significantly ablated corneal sensory neurons, exhibited delayed disease progression that was exemplified with decreased bacterial corneal burdens and altered neutrophil trafficking. Sensitization to disease was due to the increased frequencies of CGRP-induced ICAM-1+neutrophils in the infected corneas and reduced neutrophil bactericidal activities. These data showed that sensory neurons regulate corneal neutrophil responses in a tissue-specific matter affecting disease progression duringP.aeruginosakeratitis. Hence, therapeutic modalities that control nociception could beneficially impact anti-infective therapy.
Pragmática e ironía verbal: revisión crítica y claves teórico-metodológicas
Authors: De la Casa Gómez Laura
Published: May 2021

La compleja naturaleza de la ironía verbal ha llevado a los lingüistas a tratar de definirla a partir de perspectivas de análisis tan heterogéneas que la amplia bibliografía al respecto genera más dilemas de los que resuelve, ya que ninguna es por sí sola suficiente para caracterizar nítidamente la totalidad de manifestaciones irónicas posibles. A la luz de este problema teórico, en este trabajo presentamos una revisión y análisis de cinco de los modelos teóricos que, dentro de la disciplina pragmática, han tenido mayor trascendencia en el estudio de la ironía verbal. Nuestros objetivos son mostrar sus debilidades teóricas, así como los fundamentos que son potencialmente válidos, exponiendo las razones al respecto, para, a partir de las conclusiones extraídas, ofrecer algunas de las claves teóricas y metodológicas esenciales para lograr avanzar hacia una definición más unitaria, abarcadora y consistente de la ironía verbal.
El condicional periodístico en los titulares de prensa en habla hispana
Authors: Hurtado González Silvia
Published: May 2021

El objetivo de este trabajo es el análisis del condicional periodístico en el ámbito de la titulación en la prensa escrita hispanohablante. Este condicional plantea una serie de cuestiones, de diferente calado, no siempre fáciles de responder. Después de resumirlas, nos detenemos en la explicación del marco teórico siguiendo a Vatrican (2016). Posteriormente, se justifica la metodología adoptada y se explica el proceso seguido para el análisis del corpus, tras lo cual se ofrecen los resultados de la expurgación de los 360 titulares examinados, pertenecientes a artículos informativos de nueve diarios digitales de habla hispana durante los meses de febrero a mayo de 2010. Se registran casos de condicional periodístico en todos los periódicos seleccionados (siquiera en su forma simple), aunque con variaciones geográficas de interés. Una vez presentados los datos cuantitativos, se lleva a cabo una comparación entre distintos titulares con condicional periodístico y se examina su funcionamiento discursivo.
Nuevas terminaciones para nuevas realidades: performatividad, afiliación y atenuación en la comunidad de habla LGTBI
Authors: Navarro-Carrascosa Carles
Published: May 2021

Este artículo presenta un estudio sobre las terminaciones -i/-is y -e/-es en la comunidad de habla LGTBI. La motivación de esta investigación viene de la representación del género no binario en la lengua española, marcado recientemente por las terminaciones en -e, que además es utilizado para crear un plural inclusivo que evite el masculino genérico. En la misma línea, se han detectado usos, dentro de la comunidad de habla LGTBI, de otro grupo de terminaciones (-i/-is) que parecen anular la distinción de género. Los datos han sido extraídos de una encuesta sociolingüística elaborada por el autor de este trabajo. En la parte sociolingüística se pretende perfilar el tipo de usuario de estas terminaciones, hacia quiénes van dirigidas y con qué intención. En la parte pragmática se analizarán las funciones que se activan con el uso de estas terminaciones, centrando el análisis en la performatividad, la atenuación y la afiliación.
Terrorismo, delincuencia organizada y justicia transicional: Reflexiones y propuestas penales desde la Universidad de Salamanca
Authors: Matellanes Rodríguez Nuria
Published: May 2021

Esta obra recoge una amplia serie de artículos en los que se abordan temas centrales del conocido como moderno Derecho penal, que de alguna manera es la respuesta penal frente a nuevas manifestaciones de la criminalidad, consecuencia en buena medida de la evolución que en los últimos tiempos ha experimentado la sociedad. La internacionalización es una característica que condiciona el actual momento histórico y que se proyecta tanto sobre nuevos intereses que es necesario proteger, como sobre nuevas formas de delincuencia ante intereses más "tradicionales". Estos cambios necesariamente abren la puerta al debate sobre el contenido de nuevas decisiones político criminales. Desde el marco de los problemas que acarrea una posición de populismo punitivo, las aportaciones contenidas en este volumen se centran en diversas manifestaciones de la internalización de la delincuencia. Así, se ocupa de la situación que se genera por el tránsito de dictadura a democracia o la finalización de largas situaciones de conflicto interno, que ponen a la vista la comisión de delitos gravísimos contra los más elementales derechos humanos. Por otro lado, la internacionalización genera también nuevas manifestaciones de la criminalidad organizada. Es el caso del terrorismo internacional, que acusa las carencias de una definición de terrorismo universalmente aceptada y condiciona el contenido de los modelos de respuesta regionalmente aceptados, muy especialmente en el marco de la Unión Europea. Igualmente, la internacionalización de las relaciones económicas da protagonismo a las grandes corporaciones, en cuyo seno, la actividad delictiva requiere nuevas respuestas, distintas de las utilizadas hasta este momento. En esta obra se hace un estudio sobre las normas de compliance, que implican una privatización de los controles internos de la empresa y se presentan como la gran alternativa de carácter preventivo frente a la nueva delincuencia económica.