bluuebunny/crossref_metadata_2025 huggingface dataset:
Transcriptome analysis identifies genes and co-expression networks underlying heat tolerance in pigs
Authors: He Yuqing , Maltecca Christian , Tiezzi Francesco , Soto Emmanuel Lozada , Flowers William L.
Published: April 2020

Background

Heat stress adversely affects pig growth and reproduction performance by reducing feed intake, weight gain, farrowing rate, and litter size. Heat tolerance is an important characteristic in pigs, allowing them to mitigate the negative effects of heat stress on their physiological activities. Yet, genetic variation and signaling pathways associated with the biological processes of heat-tolerant pigs are currently not fully understood. This study examined differentially expressed genes and constructed gene co-expression networks on mRNAs of pigs under different heat-stress conditions using whole transcriptomic RNA-seq analyses. Semen parameters, including total sperm number per ejaculate, motility, normal morphology rate, droplets, and rejected ejaculate rate, were measured weekly on 12 boars for two time periods: thermoneutral (January to May), and heat stress (July to October). Boars were classified into heat-tolerant (n = 6) and heat-susceptible (n = 6) groups based on the variation of their ejaculate parameters across the two periods. RNA was isolated from the blood samples collected from the thermoneutral and heat stress periods for gene expression analysis.

Results

Under heat stress, a total of 66 differentially expressed genes (25 down-regulated, 41 up-regulated) were identified in heat-tolerant pigs compared to themselves during the thermoneutral period. A total of 1041 differentially expressed genes (282 down-regulated, 759 up-regulated) were identified in the comparison between heat-tolerant pigs and heat-susceptible pigs under heat stress. Weighted gene co-expression network analysis detected 4 and 7 modules with genes highly associated (r > 0.50, p < 0.05) with semen quality parameters in heat-tolerant and heat-susceptible pigs under the effects of heat stress, respectively.

Conclusion

This study utilized the sensitivity of semen to heat stress to discriminate the heat-tolerance ability of pigs. The gene expression profiles under the thermoneutral and heat stress conditions were documented in heat-tolerant and heat-susceptible boars. Findings contribute to the understanding of genes and biological mechanisms related to heat stress response in pigs and provide potential biomarkers for future investigations on the reproductive performance of pigs.
Seasonal variation in gut microbiota composition: cross-sectional evidence from Ukrainian population
Authors: Koliada Alexander , Moseiko Vladyslav , Romanenko Mariana , Piven Liubov , Lushchak Oleh , Kryzhanovska Nadiia , Guryanov Vitaly , Vaiserman Alexander
Published: April 2020

Background

Gut microbiota composition is known to depend on environmental (diet, day length, infections, xenobiotic exposure) and lifestyle (alcohol/drug intake, physical activity) factors. All these factors fluctuate seasonally, especially in areas with highly variable climatic conditions between seasons. Seasonal microbiota changes were reported in several previous studies. The purpose of our study was to investigate whether there is a seasonal variability in the gut microbiota composition in Ukrainian population. In contrast to previous studies performed on small-size samples using a longitudinal design, we used cross-sectional design with a large sample size (n = 769). Determination of microbial composition at the level of major microbial phyla was performed by qRT-PCR.

Results

The relative abundance of major taxonomic groups of gut microbiota was found to be affected by month of sampling. Actinobacteria were more abundant and Bacteroidetes were less abundant in summer-derived samples compared to those obtained during other seasons, whereas Firmicutes content was seasonally independent. The Firmicutes to Bacteroidetes (F/B) ratio was significantly higher in summer-derived samples than in winter-derived ones. Odds to have F/B > 1 were 3.3 times higher in summer samples and 1.9 times higher in autumn samples than in winter ones; neither age, nor sex were significant confounding factors.

Conclusions

Seasonality of sampling could influence results of human microbiome research, thereby potentially biasing estimates. This factor must be taken into consideration in further microbiome research.
Assessing the risk of angiotensin receptor blockers on major cardiovascular events: a systematic review and meta-analysis of randomized controlled trials
Authors: Wanas Yara , Bashir Rim , Islam Nazmul , Furuya-Kanamori Luis
Published: April 2020

Background

Angiotensin receptor blockers (ARBs) are commonly used as a treatment for many cardiovascular diseases, but their safety has been called into question. The VALUE trial found an increased risk of myocardial infarction in participants receiving ARBs compared to other antihypertensive. The aim of the meta-analysis was to synthetize the available evidence of randomised controlled trials (RCTs) and elucidate if ARBs increase the risk of cardiovascular events.

Methods

A comprehensive search was conducted to identify RCTs that assessed the safety of ARBs. Titles and abstracts of all papers were independently screened by two authors. Data extraction and quality assessment were also performed independently. The relative risk (RR) of all-cause mortality, myocardial infarction, and stroke were pooled using the IVhet model. Multiple sensitivity analyses were conducted to assess the effect of ARBs by restricting the analysis to different participants’ characteristics.

Results

Forty-five RCTs comprising of 170,794 participants were included in the analysis. The pooled estimates revealed that ARBs do not increase the risk of all-cause mortality (RR 1.00; 95%CI 0.97–1.04), myocardial infarction (RR 1.01; 95%CI 0.96–1.06), and stroke (RR 0.92; 95%CI 0.83–1.01). The sensitivity analysis did not yield a particular group of patients at increased risk of cardiovascular events with ARBs. Risk of all-cause mortality and stroke decreased with ARB when the proportion of smokers in a population was < 25% (RR 0.91; 95%CI 0.84–0.98) and in females (RR 0.76; 95%CI 0.68–0.84), respectively.

Conclusions

ARBs do not increase the risk of major cardiovascular events and are safe for use in patients.
Clinical efficacy and safety of polymyxins based versus non-polymyxins based therapies in the infections caused by carbapenem-resistant Acinetobacter baumannii: a systematic review and meta-analysis
Authors: Lyu Cheng , Zhang Yuyi , Liu Xiaofen , Wu Jufang , Zhang Jing
Published: April 2020

Background

The prevalence of infections due to carbapenem-resistant Acinetobacter baumannii (CRAB) is on the rise worldwide. Polymyxins are considered as last-resort drugs for CRAB infections, but there is still controversy regarding the efficacy and safety of polymyxins based therapies in CRAB infections. The present systematic review was designed to compare the efficacy and safety of polymyxins based therapies versus non-polymyxins based therapies in CRAB infections.

Methods

We performed a systematic literature search in PubMed, Embase, CINAHL, Cochrane Library, and clinicaltrials.gov to identify eligible studies reporting the clinical outcomes of patients with CRAB infections. The meta-analysis employed a random-effects model to estimate the odds ratio (OR) and standardized mean difference (SMD) with 95% confidence interval (CI). The primary outcome was 1-month mortality for any cause. We also examined clinical response, microbiological response, length of stay in hospital, and adverse events.

Results

Eleven eligible studies were analyzed (1052 patients in total), including 2 randomized clinical trials. Serious risk of bias was found in 8 out of the 11 studies. There was no statistically significant difference between polymyxins based therapies and non-polymyxins based therapies in 1-month mortality for any cause (OR, 0.95; 95% CI, 0.59 to 1.53), microbiological response (OR, 3.83; 95% CI, 0.90 to 16.29) and length of stay in hospital (SMD, 0.24; 95% CI, − 0.08 to 0.56). The pooled OR of clinical response indicated a significant difference in favor of polymyxin based therapies (OR, 1.99; 95% CI, 1.31 to 3.03). The pooled OR of adverse events showed that non-polymyxins based therapies were associated with fewer adverse events (OR, 4.32; 95% CI, 1.39 to 13.48).

Conclusion

The performance of polymyxins based therapies was better than non-polymyxin based therapies in clinical response rate and similar to non-polymyxin based therapies in terms of 1-month mortality and microbiological response in treating CRAB infections. Due to the limitations of our study, we cannot draw a firm conclusion on the optimal treatment of CRAB infections, but polymyxins would be a relatively effective treatment for CRAB infections. Adequate and well-designed large scale randomized controlled trials are required to clarify the relative efficacy of polymyxins based and non-polymyxins based therapies.
Retrospective observational study of salvage line ramucirumab monotherapy for patients with advanced gastric cancer
Authors: Kawai Sadayuki , Fukuda Naoki , Yamamoto Shun , Mitani Seiichiro , Omae Katsuhiro , Wakatsuki Takeru , Kato Ken , Kadowaki Shigenori , Takahari Daisuke , Boku Narikazu , Muro Kei , Machida Nozomu
Published: April 2020

Background

Ramucirumab monotherapy as a second-line treatment for advanced gastric cancer (AGC) prolongs survival compared to the best supportive care. However, in clinical practice, ramucirumab monotherapy is sometimes used as third- or later-line treatment for AGC refractory to fluoropyrimidine and taxanes. This study evaluated the efficacy and safety of salvage-line ramucirumab monotherapy for treating AGC.

Methods

The subjects of this retrospective study were advanced gastric or gastro-esophageal junction adenocarcinoma patients who received ramucirumab monotherapy after failure of 2 or more prior regimens containing fluoropyrimidine and taxanes but not ramucirumab.

Results

From June 2015 to April 2017, 51 patients were enrolled. The median progression-free survival (PFS) and overall survival (OS) were 1.8 (95% confidence interval [CI] = 1.6–2.2) and 5.1 (95% CI = 4.0–6.8) months, respectively. The objective response and disease control rates were 2 and 17%, respectively. Grade 3 adverse events (AEs; e.g., anemia, fatigue, hypertension, proteinuria, intestinal bleeding) occurred in seven (13%) patients, but no grade 4 AEs and treatment-related deaths were observed. A neutrophil–lymphocyte ratio (NLR) of < 2.5 and previous gastrectomy were associated with better PFS.

Conclusions

Salvage-line ramucirumab monotherapy has acceptable toxicity and comparable efficacy to second-line treatment; therefore, we consider physicians might choose this therapy as a salvage-line treatment option for AGC refractory to the standard therapies.
Effects of self-assessed chewing ability, tooth loss and serum albumin on mortality in 80-year-old individuals: a 20-year follow-up study
Authors: Nomura Yoshiaki , Kakuta Erika , Okada Ayako , Otsuka Ryoko , Shimada Mieko , Tomizawa Yasuko , Taguchi Chieko , Arikawa Kazumune , Daikoku Hideki , Sato Tamotsu , Hanada Nobuhiro
Published: April 2020

Background

The association between dental status and mortality in community-dwelling older adults has been documented by several studies. The aim of this study was to analyze the contribution of self-assessed chewing ability, number of remaining teeth and serum albumin levels to mortality and the interactions between the three factors.

Methods

A 20-year follow-up study was conducted with 666 subjects aged 80 years (from 1996 to 2017) who resided in the 8 areas served by one health center in Iwate Prefecture. Health check-ups including physical fitness measurements were conducted at a meeting place or gymnasium. Medical interview and blood sampling were conducted by physician. Oral examination was examined by dentist. The number of remaining teeth, serum albumin levels, and self-assessed chewing ability were used as predictors of mortality.

Results

Among the 608 subjects (233 men and 375 women) included in this study, only 12 subjects (1.97%) survived after 20 years of follow-up. For men, dental status and serum levels of albumin were significantly associated with mortality. The hazard ratios of self-assessed chewing ability calculated by item response theory analysis and the inability to chew at least one food adjusted for serum albumin and tooth conditions were statistically significant in men. When adjusted by health status evaluated by blood tests, self-assessed chewing ability was statistically significant in men. According to path analysis, self-assessed chewing ability and serum albumin independently affected mortality in men.

Conclusion

Masticatory dysfunction may be an important risk factor for mortality in men, even though it was self-assessed. Retaining chewing ability might be a useful predictor of longevity in older male adults.
RETRACTED ARTICLE: Astragalin alleviates cerebral ischemia-reperfusion injury by improving anti-oxidant and anti-inflammatory activities and inhibiting apoptosis pathway in rats
Authors: Chen Xiuying , Cheng Chang , Zuo Xuzheng , Huang Wen
Published: April 2020

Background

Astragalin (AG), a flavonoid from many traditional herbs and medicinal plants, has been described to exhibit in vitro anti-inflammatory activity. The paper aimed to study the effects of astragalin on anti-inflammatory, anti-oxidative ability and apoptosis signaling pathway in brain tissue of rats with cerebral ischemia-reperfusion injury, and to explore its possible mechanism.

Methods

The rat model of focal cerebral ischemia-reperfusion injury was established by suture method. It was randomly divided into 5 groups, sham operation group, ischemia-reperfusion (I/R) treatment group, and astragalin treatment I / R group (12.5, 25, 50 mg / kg). After 24 h of reperfusion, the neurological deficits of the rats were analyzed and HE staining was performed. The volume of cerebral infarction was calculated by triphenyltetrazolium chloride (TTC) staining, and the apoptosis of nerve cells was detected by TUNEL staining. In addition, the content of malondialdehyde (MDA), nitric oxide (NO), superoxide dismutase (SOD), glutathione (GSH) assay and glutathione peroxidase (GSH-Px) were measured in rat brain tissue. Western blot analysis was used to determine the expression of related proteins.

Results

Compared with I/R group, the neurological deficit score and infarct volume of I/R rats were reduced in the astragalin treatment group. In the astragalin treatment group, MDA and NO levels in I/R rats were reduced, antioxidant enzymes and superoxide dismutase (SOD) activity were increased. In the astragalin treatment group, NF-κB (p65) and cyclooxygenase-2 (COX-2) expression levels were down-regulated, NF-E2-related factor 2 (Nrf2) nucleus and heme oxygenase-1 (HO-1) protein expression levels were up-regulated. In addition, the astragalin treatment can inhibit apoptosis, down-regulate Bax and cleaved caspase-3 expression, up-regulate Bcl-Xl expression.

Conclusion

The antioxidant properties of astragalin may play an important role in improving cerebral ischemia-reperfusion injury.
Responsiveness and minimal clinically important difference of SGRQ-I and K-BILD in idiopathic pulmonary fibrosis
Authors: Prior Thomas Skovhus , Hoyer Nils , Hilberg Ole , Shaker Saher Burhan , Davidsen Jesper Rømhild , Bendstrup Elisabeth
Published: April 2020

Background

Idiopathic pulmonary fibrosis (IPF) specific version of St. George’s Respiratory Questionnaire (SGRQ-I) and King’s Brief Interstitial Lung Disease questionnaire (K-BILD) are validated health-related quality of life (HRQL) instruments, but no or limited data exist on their responsiveness and minimal clinically important difference (MCID). The objectives of this study were to assess responsiveness of SGRQ-I and K-BILD and determine MCID separately for deterioration and improvement in a large, prospective cohort of patients with IPF in a real-world setting.

Methods

Consecutive patients with IPF were recruited. SGRQ-I, K-BILD, SGRQ, Shortness of Breath Questionnaire, pulmonary function tests and 6-min walk test measurements were obtained at baseline and at six and 12 months; at six and 12 months, patients also completed Global Rating of Change Scales. Responsiveness was assessed using correlation coefficients and linear regression. Cox regression was used for mortality analyses. MCID was estimated using receiver operating characteristic curves with separate analyses for improvement and deterioration.

Results

A total of 150 IPF patients were included and 124 completed the 12-month follow-up. Based on all HRQL anchors and most physiological anchors, responsiveness analyses supported the evidence pointing towards SGRQ-I and K-BILD as responsive instruments. Multivariate analyses showed an association between SGRQ-I and mortality (HR: 1.18, 95% CI: 1.02 to 1.36, p = 0.03) and a trend was found for K-BILD (HR: 0.82, 95% CI: 0.64 to 1.05, p = 0.12). MCID was estimated for all domains of SGRQ-I and K-BILD. MCID for improvement differed from deterioration for both SGRQ-I Total (3.9 and 4.9) and K-BILD Total (4.7 and 2.7).

Conclusions

SGRQ-I and K-BILD were responsive to change concerning both HRQL and most physiological anchors. MCID was determined separately for improvement and deterioration, resulting in different estimates; especially a smaller estimate for deterioration compared to improvement in K-BILD.

Trial registration

Clinicaltrials.gov, no. NCT02818712. Registered 30 June 2016.
Dietary patterns and their associations with gestational weight gain in the United Arab Emirates: results from the MISC cohort
Authors: Itani Leila , Radwan Hadia , Hashim Mona , Hasan Hayder , Obaid Reyad Shaker , Ghazal Hessa Al , Al Hilali Marwa , Rayess Rana , Mohamed Hamid Jan Jan , Hamadeh Rena , Al Rifai Hiba , Naja Farah
Published: April 2020

Background

Suboptimum weight gain during pregnancy may carry long term health consequences for the infant or mother. Nutritional imbalances are well recognized as a determinant of gestational weight gain. Few studies examined the effect of dietary patterns on gestational weight gain, especially in countries undergoing nutrition transition, such as the United Arab Emirates.

Objectives

To characterize dietary patterns among pregnant women living in the UAE and examine their associations with gestational weight gain and gestational weight rate.

Methodology

Data were drawn from the Mother-Infant Study Cohort, a two-year prospective cohort study of pregnant women living in the United Arab Emirates, recruited during their third trimester (n = 242). Weight gain during pregnancy was calculated using data from medical records. The Institute of Medicine’s recommendations were used to categorize gestational weight gain and gestational weight gain rate into insufficient, adequate, and excessive. During face-to-face interviews, dietary intake was assessed using an 89-item culture-specific semi-quantitative food frequency questionnaire that referred to usual intake during pregnancy. Dietary patterns were derived by principal component analysis. Multiple logistic regression analyses were used to evaluate the associations of derived dietary patterns with gestational weight gain/gestational weight gain rate.

Results

Two dietary patterns were derived, a “Diverse” and a “Western” pattern. The “Diverse” pattern was characterized by higher intake of fruits, vegetables, mixed dishes while the “Western” pattern consisted of sweets and fast food. The “Western” pattern was associated with excessive gestational weight gain (OR:4.04,95% CI:1.07–15.24) and gestational weight gain rate (OR: 4.38, 95% CI:1.28–15.03) while the “Diverse” pattern decreased the risk of inadequate gestational weight gain (OR:0.24, 95% CI:0.06–0.97) and gestational weight gain rate (OR:0.28, 95% CI:0.09–0.90).

Conclusion

The findings of this study showed that adherence to a “Diverse” pattern reduced the risk of insufficient gestational weight gain/gestational weight gain rate, while higher consumption of the “Western” pattern increased the risk of excessive gestational weight gain/gestational weight gain rate. In view of the established consequences of gestational weight gain on the health of the mother and child, there is a critical need for health policies and interventions to promote a healthy lifestyle eating through a life course approach.
Correction to: A geographic identifier assignment algorithm with Bayesian variable selection to identify neighborhood factors associated with emergency department visit disparities for asthma
Authors: Bozigar Matthew , Lawson Andrew , Pearce John , King Kathryn , Svendsen Erik
Published: April 2020

Unfortunately, the original version of the article [1] contained an error. A typo in the main equation (Eq. 1) has been introduced during the production process. The operator “ = ” in Eq. 1 “log(θik) =  α + ui…” was missing.
Ulcerative colitis: understanding its cellular pathology could provide insights into novel therapies
Authors: Kaur Amandip , Goggolidou Paraskevi
Published: April 2020

Dynamic interactions between the gastrointestinal epithelium and the mucosal immune system normally contribute to ensuring intestinal homeostasis and optimal immunosurveillance, but destabilisation of these interactions in genetically predisposed individuals can lead to the development of chronic inflammatory diseases. Ulcerative colitis is one of the main types of inflammatory diseases that affect the bowel, but its pathogenesis has yet to be completely defined. Several genetic factors and other inflammation-related genes are implicated in mediating the inflammation and development of the disease. Some susceptibility loci associated with increased risk of ulcerative colitis are found to be implicated in mucosal barrier function. Different biomarkers that cause damage to the colonic mucosa can be detected in patients, including perinuclear ANCA, which is also useful in distinguishing ulcerative colitis from other colitides. The choice of treatment for ulcerative colitis depends on disease severity. Therapeutic strategies include anti-tumour necrosis factor alpha (TNF-α) monoclonal antibodies used to block the production of TNF-α that mediates intestinal tract inflammation, an anti-adhesion drug that prevents lymphocyte infiltration from the blood into the inflamed gut, inhibitors of JAK1 and JAK3 that suppress the innate immune cell signalling and interferons α/β which stimulate the production of anti-inflammatory cytokines, as well as faecal microbiota transplantation. Although further research is still required to fully dissect the pathophysiology of ulcerative colitis, understanding its cellular pathology and molecular mechanisms has already proven beneficial and it has got the potential to identify further novel, effective targets for therapy and reduce the burden of this chronic disease.
Disulfide isomerase ERp57 improves the stability and immunogenicity of H3N2 influenza virus hemagglutinin
Authors: Wu Jialing , Wang Yang , Wei Ying , Xu Zhichao , Tan Xin , Wu Zhihui , Zheng Jing , Liu George Dacai , Cao Yongchang , Xue Chunyi
Published: April 2020

Background

Hemagglutinin (HA), as the surface immunogenic protein, is the most important component of influenza viruses. Previous studies showed that the stability of HA was significant for HA’s immunogenicity, and many efforts have been made to stabilize the expressed HA proteins.

Methods

In this study, the protein disulfide isomerases (PDIs) were investigated for the ability to improve the stability of HA protein. Two members of the PDIs family, PDI and ERp57, were over-expressed or down-expressed in 293 T cells. The expression of H3 HA and PDIs were investigated by real-time qPCR, western-blot, immunofluorescence assay, and flow cytometry. The stability of HA was investigated by western-blot under non-reducing condition. Moreover, BALB/c mice were immunized subcutaneously twice with the vaccine that contained HA proteins from the ERp57-overexpressed and conventional 293 T cells respectively to investigate the impact of ERp57 on the immunogenicity of H3N2 HA.

Results

The percentage of the disulfide-bonded HA trimers increased significantly in the PDIs-overexpressed 293 T cells, and ERp57 was more valid to the stability of HA than PDI. The knockdown of ERp57 by small interfering RNA significantly decreased the percentage of the disulfide-bonded HA trimers. HA proteins from ERp57-overexpressed 293 T cells stimulated the mice to generate significantly higher HA-specific IgG against H1N1 and H3N2 viruses than those from the conventional cells. The mice receiving H3 HA from ERp57-overexpressed 293 T cells showed the better resistance against H1N1 viruses and the higher survival rate than the mice receiving H3 HA from the conventional cells.

Conclusion

ERp57 could improve the stability and immunogenicity of H3N2 HA.
An efficient in vitro regeneration system from different wild apple (Malus sieversii) explants
Authors: Zhang Y. , Bozorov T. A. , Li D. X. , Zhou P. , Wen X. J. , Ding Y. , Zhang D. Y.
Published: April 2020

Background

Wild apple, Malus sieversii, is an endangered species and a valuable genetic resource that requires a variety of conservation techniques. This study aimed to investigate the influence of different concentrations of hormones on wild apple regeneration from leaf and stem explants to establish an optimal regeneration system.

Results

Leaves and stems derived from seedlings were cultured on several media supplemented with various concentrations of thidiazuron (TDZ) or 6-benzylaminopurine (BA) in different combinations with 1-naphthaleneacetic acid (NAA). The results showed that the most efficient shoot formation media (35% and 90%) were MS medium containing 4.0 mg L−1 TDZ and 1.0 mg L−1 NAA for leaf explants and MS medium containing 1.0 mg L−1 BA without NAA for stem explant. MS medium supplemented with 0.4 mg L−1 BA and 0.1 mg L−1 NAA (for shoot multiplication) and 1/2 MS + 0.1 mg L−1 NAA + 1.5% sucrose (for rooting) were effective media. Shoot regeneration from leaf explants was the most effective when the explants were placed abaxial side down onto the medium and were subjected to a pre-treatment of 3 weeks in darkness.

Conclusions

An optimized regeneration system for M. sieversii that allowed regeneration within 2–3 months developed. The protocol developed herein can be used in large-scale clonal propagation for the conservation of wild apple, M. sieversii.
Different applications of the KDIGO criteria for AKI lead to different incidences in critically ill patients: a post hoc analysis from the prospective observational SICS-II study
Authors: Wiersema Renske , Jukarainen Sakari , Eck Ruben J. , Kaufmann Thomas , Koeze Jacqueline , Keus Frederik , Pettilä Ville , van der Horst Iwan C. C. , Vaara Suvi T.
Published: April 2020

Background

Acute kidney injury (AKI) is a frequent and clinically relevant problem in critically ill patients. Various randomized controlled trials (RCT) have attempted to assess potentially beneficial treatments for AKI. Different approaches to applying the Kidney Disease Improving Global Outcomes (KDIGO) criteria for AKI make a comparison of studies difficult. The objective of this study was to assess how different approaches may impact estimates of AKI incidence and whether the association between AKI and 90-day mortality varied by the approach used.

Methods

Consecutive acutely admitted adult intensive care patients were included in a prospective observational study. AKI was determined following the KDIGO criteria during the first 7 days of ICU admission. In this post hoc analysis, we assessed whether AKI incidence differed when applying the KDIGO criteria in 30 different possible methods, varying in (A) serum creatinine (sCr), (B) urine output (UO), and (C) the method of combining these two into an outcome, e.g., severe AKI. We assessed point estimates and 95% confidence intervals for each incidence. Univariable regression was used to assess the associations between AKI and 90-day mortality.

Results

A total of 1010 patients were included. Baseline creatinine was available in 449 (44%) patients. The incidence of any AKI ranged from 28% (95%CI 25–31%) to 75% (95%CI 72–77%) depending on the approach used. Methods to estimate missing baseline sCr caused a variation in AKI incidence up to 15%. Different methods of handling UO caused a variation of up to 35%. At 90 days, 263 patients (26%) had died, and all 30 variations were associated with 90-day mortality.

Conclusions

In this cohort of critically ill patients, AKI incidence varied from 28 to 75%, depending on the method used of applying the KDIGO criteria. A tighter adherence to KDIGO definitions is warranted to decrease the heterogeneity of AKI and increase the comparability of future studies.
Improved lipid productivity in Nannochloropsis gaditana in nitrogen-replete conditions by selection of pale green mutants
Authors: Cecchin Michela , Berteotti Silvia , Paltrinieri Stefania , Vigliante Ivano , Iadarola Barbara , Giovannone Barbara , Maffei Massimo E. , Delledonne Massimo , Ballottari Matteo
Published: April 2020

Background

Nannochloropsis gaditana is a photosynthetic unicellular microalgae considered one of the most interesting marine algae to produce biofuels and food additive due to its rapid growth rate and high lipid accumulation. Although microalgae are attractive platforms for solar energy bioconversion, the overall efficiency of photosynthesis is reduced due to the steep light gradient in photobioreactors. Moreover, accumulation of lipids in microalgae for biofuels production is usually induced in a two-phase cultivation process by nutrient starvation, with additional time and costs associated. In this work, a biotechnological approach was directed for the isolation of strains with improved light penetration in photobioreactor combined with increased lipids productivity.

Results

Mutants of Nannochloropsis gaditana were obtained by chemical mutagenesis and screened for having both a reduced chlorophyll content per cell and increased affinity for Nile red, a fluorescent dye which binds to cellular lipid fraction. Accordingly, one mutant, called e8, was selected and characterized for having a 30% reduction of chlorophyll content per cell and an almost 80% increase of lipid productivity compared to WT in nutrient-replete conditions, with C16:0 and C18:0 fatty acids being more than doubled in the mutant. Whole-genome sequencing revealed mutations in 234 genes in e8 mutant among which there is a non-conservative mutation in the dgd1 synthase gene. This gene encodes for an enzyme involved in the biosynthesis of DGDG, one of the major lipids found in the thylakoid membrane and it is thus involved in chloroplast biogenesis. Lipid biosynthesis is strongly influenced by light availability in several microalgae species, including Nannochloropsis gaditana: reduced chlorophyll content per cell and more homogenous irradiance in photobioreactor is at the base for the increased lipid productivity observed in the e8 mutant.

Conclusions

The results herein obtained presents a promising strategy to produce algal biomass enriched in lipid fraction to be used for biofuel and biodiesel production in a single cultivation process, without the additional complexity of the nutrient starvation phase. Genome sequencing and identification of the mutations introduced in e8 mutant suggest possible genes responsible for the observed phenotypes, identifying putative target for future complementation and biotechnological application.
Latest trends in L. infantum infection in dogs in Spain, Part II: current clinical management and control according to a national survey of veterinary practitioners
Authors: Montoya Ana , Gálvez Rosa , Checa Rocío , Sarquis Juliana , Plaza Alexandra , Barrera Juan Pedro , Marino Valentina , Miró Guadalupe
Published: April 2020

Background

Canine leishmaniosis (CanL) is a parasitic zoonotic disease, endemic in the Mediterranean basin including Spain. While knowledge about CanL, its management, treatment, prevention and control mounts, it remains unclear whether all clinical veterinarians follow the same international recommendations, such as those of the LeishVet group. This study was thus designed to assess recent trends in the clinical management of CanL in veterinary clinics across Spain through a questionnaire-based survey. Results were compared with those of a prior national multicenter questionnaire administered by our research team in 2005.

Methods

A questionnaire consisting of 28 questions about CanL was developed using Google Forms and distributed by email to 1428 veterinary clinics in Spain. Questions were designed to obtain data on common clinical signs, techniques and complementary exams used to diagnose the disease, and on its monitoring, treatment and control measures. Data were collected in a database for statistical analysis.

Results

Completed questionnaires were returned by 295 clinics. Compared to the situation in 2005, responses indicate that clinical signs of CanL have not changed significantly, cutaneous lesions being still the most prevalent sign observed by practitioners. Quantitative serological techniques are considered an adequate approach to diagnosis, provided their results are supported by the findings of a thorough physical exam, as well as complementary tests (complete blood count, biochemical profile, plasma protein electrophoretogram and complete urinalysis). Treatment protocols and check-ups follow international recommendations. Finally, a multimodal approach is being endorsed to adequately control CanL including preventive measures such as annual serological check-ups and the combination of repellents and vaccines. Additionally, owners are being better informed about CanL by veterinarians, which translates to the improved control of this zoonosis.

Conclusions

The clinical management of CanL has recently undergone significant changes owing to improvements in clinical knowledge of the disease, more unified international criteria, improved diagnostic techniques and their adequate interpretation, as well as a greater awareness of the disease transmitted to owners.
Shallow whole-genome sequencing of plasma cell-free DNA accurately differentiates small from non-small cell lung carcinoma
Authors: Raman Lennart , Van der Linden Malaïka , Van der Eecken Kim , Vermaelen Karim , Demedts Ingel , Surmont Veerle , Himpe Ulrike , Dedeurwaerdere Franceska , Ferdinande Liesbeth , Lievens Yolande , Claes Kathleen , Menten Björn , Van Dorpe Jo
Published: April 2020

Background

Accurate lung cancer classification is crucial to guide therapeutic decisions. However, histological subtyping by pathologists requires tumor tissue—a necessity that is often intrinsically associated with procedural difficulties. The analysis of circulating tumor DNA present in minimal-invasive blood samples, referred to as liquid biopsies, could therefore emerge as an attractive alternative.

Methods

Concerning adenocarcinoma, squamous cell carcinoma, and small cell carcinoma, our proof of concept study investigates the potential of liquid biopsy-derived copy number alterations, derived from single-end shallow whole-genome sequencing (coverage 0.1–0.5×), across 51 advanced stage lung cancer patients.

Results

Genomic abnormality testing reveals anomalies in 86.3% of the liquid biopsies (16/20 for adenocarcinoma, 13/16 for squamous cell, and 15/15 for small cell carcinoma). We demonstrate that copy number profiles from formalin-fixed paraffin-embedded tumor biopsies are well represented by their liquid equivalent. This is especially valid within the small cell carcinoma group, where paired profiles have an average Pearson correlation of 0.86 (95% CI 0.79–0.93). A predictive model trained with public data, derived from 843 tissue biopsies, shows that liquid biopsies exhibit multiple deviations that reflect histological classification. Most notably, distinguishing small from non-small cell lung cancer is characterized by an area under the curve of 0.98 during receiver operating characteristic analysis. Additionally, we investigated how deeper paired-end sequencing, which will eventually become feasible for routine diagnosis, empowers tumor read enrichment by insert size filtering: for all of the 29 resequenced liquid biopsies, the tumor fraction could be increased in silico, thereby “rescuing” three out of five cases with previously undetectable alterations.

Conclusions

Copy number profiling of cell-free DNA enables histological classification. Since shallow whole-genome sequencing is inexpensive and often fully operational at routine molecular laboratories, this finding has current diagnostic potential, especially for patients with lesions that are difficult to reach.
Diverse transposable element landscapes in pathogenic and nonpathogenic yeast models: the value of a comparative perspective
Authors: Maxwell Patrick H.
Published: April 2020

Genomics and other large-scale analyses have drawn increasing attention to the potential impacts of transposable elements (TEs) on their host genomes. However, it remains challenging to transition from identifying potential roles to clearly demonstrating the level of impact TEs have on genome evolution and possible functions that they contribute to their host organisms. I summarize TE content and distribution in four well-characterized yeast model systems in this review: the pathogensCandida albicansandCryptococcus neoformans, and the nonpathogenic speciesSaccharomyces cerevisiaeandSchizosaccharomyces pombe. I compare and contrast their TE landscapes to their lifecycles, genomic features, as well as the presence and nature of RNA interference pathways in each species to highlight the valuable diversity represented by these models for functional studies of TEs. I then review the regulation and impacts of the Ty1 and Ty3 retrotransposons fromSaccharomyces cerevisiaeand Tf1 and Tf2 retrotransposons fromSchizosaccharomyces pombeto emphasize parallels and distinctions between these well-studied elements. I propose that further characterization of TEs in the pathogenic yeasts would enable this set of four yeast species to become an excellent set of models for comparative functional studies to address outstanding questions about TE-host relationships.
Genome-wide DNA methylation profiles of low- and high-grade adenoma reveals potential biomarkers for early detection of colorectal carcinoma
Authors: Fan Jian , Li Jun , Guo Shicheng , Tao Chengcheng , Zhang Haikun , Wang Wenjing , Zhang Ying , Zhang Dake , Ding Shigang , Zeng Changqing
Published: April 2020

Background

Abnormal DNA methylation is a hallmark of human cancers and may be a promising biomarker for early diagnosis of human cancers. However, the majority of DNA methylation biomarkers that have been identified are based on the hypothesis that early differential methylation regions (DMRs) are maintained throughout carcinogenesis and could be detected at all stages of cancer.

Methods

In this study, we identified potential early biomarkers of colorectal cancer (CRC) development by genome-wide DNA methylation assay (Illumina infinium450, 450 K) of normal (N = 20) and pre-colorectal cancer samples including 18 low-grade adenoma (LGA) and 22 high-grade adenoma (HGA), integrated with GEO and ArrayExpress datasets (N = 833).

Results

We identified 209 and 8692 CpG sites that were significantly hyper-methylated in LGA and HGA, respectively. Pathway analysis identified nervous system-related methylation changes that are significantly associated with early adenoma development. Integration analysis revealed that DNA methylation in the promoter region of ADHFE1 has the most potential for being an early diagnostic biomarker for colorectal adenoma and cancer (sensitivity = 0.96, specificity = 0.95, area under the curve = 0.97).

Conclusions

Overall, we demonstrated that DNA methylation have been shown significant changes in the stage of LGA and HGA in the development of colon cancer. Genome-wide DNA methylation to LGA and HGA provided an important proxy to identify promising early diagnosis biomarkers for colorectal cancer.
Emerging proteomic approaches to identify the underlying pathophysiology of neurodevelopmental and neurodegenerative disorders
Authors: Murtaza Nadeem , Uy Jarryll , Singh Karun K.
Published: April 2020

Proteomics is the large-scale study of the total protein content and their overall function within a cell through multiple facets of research. Advancements in proteomic methods have moved past the simple quantification of proteins to the identification of post-translational modifications (PTMs) and the ability to probe interactions between these proteins, spatially and temporally. Increased sensitivity and resolution of mass spectrometers and sample preparation protocols have drastically reduced the large amount of cells required and the experimental variability that had previously hindered its use in studying human neurological disorders. Proteomics offers a new perspective to study the altered molecular pathways and networks that are associated with autism spectrum disorders (ASD). The differences between the transcriptome and proteome, combined with the various types of post-translation modifications that regulate protein function and localization, highlight a novel level of research that has not been appropriately investigated. In this review, we will discuss strategies using proteomics to study ASD and other neurological disorders, with a focus on how these approaches can be combined with induced pluripotent stem cell (iPSC) studies. Proteomic analysis of iPSC-derived neurons have already been used to measure changes in the proteome caused by patient mutations, analyze changes in PTMs that resulted in altered biological pathways, and identify potential biomarkers. Further advancements in both proteomic techniques and human iPSC differentiation protocols will continue to push the field towards better understanding ASD disease pathophysiology. Proteomics using iPSC-derived neurons from individuals with ASD offers a window for observing the altered proteome, which is necessary in the future development of therapeutics against specific targets.
The scope of tobacco cessation randomized controlled trials in low- to middle-income countries: protocol for a scoping review
Authors: Kumar Navin , Ainooson Jessica , Billings Ameera , Chen Grace , Cueto Lauren , Janmohamed Kamila , Jiang Jeannette , Niaura Raymond , Zhang Amy
Published: April 2020

Background

Tobacco consumption is the leading cause of preventable death globally. The global mortality burden of tobacco use lies predominantly in low- to middle-income countries (LMICs). There is much evidence on the effectiveness of tobacco cessation RCTs in high-income nations. However, the evidence base in LMICs is far more limited. To effectively design randomized controlled trials (RCTs) that mitigate tobacco-related harms in LMICs, further understanding of RCTs in this environment will be helpful. We will provide quality evidence regarding the scope of tobacco cessation RCTs in LMICs.

Methods

A scoping review of tobacco cessation RCTs will be conducted. MEDLINE, Embase, PsycINFO, Global Health, Web of Science and Sociological Abstracts will be searched to capture current literature. We will review RCTs that have already been done on tobacco cessation in the LMICs. The key outcome will be tobacco cessation in adults. Examples of the key outcome include smoking abstinence and reduction of tobacco use. Study selection will conform to Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews (PRISMA-ScR) guidelines and study quality assessed with a modified version of the Cochrane Collaboration’s instrument.

Discussion

As researchers attempt to minimize the harms from tobacco in LMICs, they need to be aware of scientific evidence to develop RCTs to achieve their aim. The review will complement the evidence base on tobacco cessation in LMICs.
Refinements of the integral form of Jensen’s and the Lah–Ribarič inequalities and applications for Csiszár divergence
Authors: Pečarić J. , Perić J.
Published: April 2020

In this paper, we give refinements of the integral form of Jensen’s inequality and the Lah–Ribarič inequality. Using these results, we obtain a refinement of the Hölder inequality and a refinement of some inequalities for integral power means and quasiarithmetic means. We also give applications in information theory, namely, we give some interesting estimates for the integral Csiszár divergence and its important particular cases.
Correction to: Molecular characterization of multidrug-resistant Mycobacterium tuberculosis (MDR-TB) isolates identifies local transmission of infection in Kuwait, a country with a low incidence of TB and MDR-TB
Authors: Al-Mutairi Noura M. , Ahmad Suhail , Mokaddas Eiman M.
Published: April 2020

The original publication of this article [1] contained few erroneous paragraphs and errors in Table 1 and Table 2. The first four paragraphs are in the ‘Results’ section while the last four paragraphs are in the ‘Discussion’ section. The errors in Table 1 involve the number of isolates tested for pyrazinamide and pyrazinamide susceptible isolates, ethambutol-susceptible isolates with a mutation and number of resistant isolates with a mutation for streptomycin. The error in Table 2 involves wrong codon number for a mutation in isolate KM17-01 in Cluster XII for gidB gene. The updated informations have been indicated in bold and also refer corrected Tables 1 and 2.
CNV analysis of Meishan pig by next-generation sequencing and effects of AHR gene CNV on pig reproductive traits
Authors: Zheng Xianrui , Zhao Pengju , Yang Kaijie , Ning Chao , Wang Haifei , Zhou Lei , Liu Jianfeng
Published: April 2020

Background

Reproductive performance of livestock is an economically important aspect of global food production. The Chinese Meishan pig is a prolific breed, with an average of three to five more piglets per litter than European breeds; however, the genetic basis for this difference is not well understood.

Results

In this study, we investigated copy number variations (CNVs) of 32 Meishan pigs and 29 Duroc pigs by next-generation sequencing. A genome-wide analysis of 61 pigs revealed 12,668 copy number variable regions (CNVRs) that were further divided into three categories based on copy number (CN) of the whole population, i.e., gain (n = 7,638), and loss (n = 5,030) CNVRs. We then compared Meishan and Duroc pigs and identified 17.17 Mb of 6,387 CNVRs that only existing in Meishan pigs CNVRs that overlapped the reproduction-related gene encoding the aryl hydrocarbon receptor (AHR) gene. We found that normal AHR CN was more frequent than CN loss in four different pig breeds. An association analysis showed that AHR CN had a positive effect on litter size (P < 0.05) and that a higher CN was associated with higher total number born (P < 0.05), number born alive (P < 0.05), number of weaned piglets, and birth weight.

Conclusions

The present study provides comprehensive CNVRs for Meishan and Duroc pigs through large-scale population resequencing. Our results provide a supplement for the high-resolution map of copy number variation in the porcine genome and valuable information for the investigation of genomic structural variation underlying traits of interest in pig. In addition, the association results provide evidence for AHR as a candidate gene associated with reproductive traits that can be used as a genetic marker in pig breeding programs.