bluuebunny/crossref_metadata_2025 huggingface dataset:
Identification of MTHFD2 as a novel prognosis biomarker in esophageal carcinoma patients based on transcriptomic data and methylation profiling
Authors: Wang Jianlin , Luo Judong , Sun Zhiqiang , Sun Fei , Kong Ze , Yu Jingping
Published: September 2020

DNA methylation is an important epigenetic regulatory mechanism in esophageal carcinoma (EC) and is associated with genomic instability and carcinogenesis. In the present study, we aimed to identify tumor biomarkers for predicting prognosis of EC patients.

We downloaded mRNA expression profiles and DNA methylation profiles associated with EC from the Gene Expression Omnibus database. Differentially expressed and differentially methylated genes between tumor tissues and adjacent normal tissue samples were identified. Functional enrichment analyses were performed, followed by the construction of protein–protein interaction networks. Data were validated based on methylation profiles from The Cancer Genome Atlas. Candidate genes were further verified according to survival analysis and Cox regression analysis.

We uncovered multiple genes with differential expression or methylation in tumor samples compared with normal samples. After taking the intersection of 3 differential gene sets, we obtained a total of 232 overlapping genes. Functional enrichment analysis revealed that these genes are related to pathways such as “glutathione metabolism,” “p53 signaling pathway,” and “focal adhesion.” Furthermore, 8 hub genes with inversed expression and methylation correlation were identified as candidate genes. The abnormal expression levels of MSN, PELI1, and MTHFD2 were correlated with overall survival times in EC patients (P < .05). Only MTHFD2 was significantly associated with a pathologic stage according to univariate analysis (P = .037) and multivariate analysis (P = .043).

Our study identified several novel EC biomarkers with prognostic value by integrated analysis of transcriptomic data and methylation profiles. MTHFD2 could serve as an independent biomarker for predicting prognosis and pathological stages of EC.
Intra-abdominal fat accumulation is an important predictor of metabolic syndrome in young adults
Authors: Kobayashi Masakazu , Ogawa Sayaka , Tayama Jun , Sagara Ikuko , Takeoka Atsushi , Bernick Peter , Kawano Tetsuya , Abiru Norio , Hayashida Masaki , Shirabe Susumu
Published: September 2020

Metabolic syndrome (MetS), mainly caused by intra-abdominal fat (IAF) accumulation, is an important risk factor for cardiovascular disease. The prevalence of MetS increases rapidly after the age of 40 years, and it is presumed that there is a substantial proportion of MetS in younger age groups. However, the association of IAF with MetS in adults aged 20 to 30 years has not been fully investigated.

This study aimed to determine the prevalence of MetS and to verify whether IAF accumulation is associated with other MetS-related metabolic disorders including dyslipidemia, high blood pressure, and high blood glucose among the Japanese population in their 20s.

In this cross-sectional study, IAF area (IAFA) and MetS-related metabolic parameters were evaluated in university students in their 20s (n = 1822, 21.5 ± 1.5 years). IAFA was measured using a non-invasive device, DUALSCAN, which can be readily measured through the dual impedance method. The participants were divided into four groups according to IAFA: 0–49.9, 50–74.9, 75–99.9, and ≥100 cm2.

MetS was prevalent in 3.3% and 0.0% of the males and females, respectively, according to the Japanese criteria of MetS. The sex- and lifestyle-adjusted odds ratios (ORs) for the three metabolic component levels of Mets were elevated in the larger IAFA groups compared to the smallest IAFA group, according to the level of IAFA. The levels particularly increased in participants with abdominal obesity, defined by both, IAFA and waist circumference rather than by waist circumference alone.

IAF accumulation was significantly associated with MetS-related metabolic disorders in young adults. An evaluation of IAFA may contribute to the early prediction of the risk of developing MetS in the future.
Modified grade 4 osteotomy for the correction of post-traumatic thoracolumbar kyphosis
Authors: Liu Feng-Yu , Gu Zhen-Fang , Zhao Zheng-Qi , Ren Liang , Wang Li-Min , Yu Jin-He , Hou Shu-Bing , Ding Wen-Yuan , Sun Xian-Ze
Published: September 2020

Many surgical procedures have been developed for the treatment of post-traumatic thoracolumbar kyphosis. But there is a significant controversy over the ideal management. The aim of this study was to illustrate the technique of modified grade 4 osteotomy for the treatment of post-traumatic thoracolumbar kyphosis and to evaluate clinical and radiographic results of patients treated with this technique.

From May 2013 to May 2018, 42 consecutive patients experiencing post-traumatic thoracolumbar kyphosis underwent the technique of modified grade 4 osteotomy, and their medical records were retrospectively collected. Preoperative and postoperative sagittal Cobb angle, visual analog scale (VAS), Oswestry disability index (ODI), and American Spinal Injury Association (ASIA) were recorded. The average follow-up period was 29.7 ± 14.2 months.

The operation time was 185.5 ± 26.8 minutes, the intraoperative blood loss was 545.2 ± 150.1 mL. The Cobb angles decreased from 38.5 ± 3.8 degree preoperatively to 4.2 ± 2.6 degree 2 weeks after surgery (P < .001). The VAS reduced from 6.5 ± 1.1 preoperatively to 1.5 ± 0.9 at final follow-up (P < .001), and the ODI reduced from 59.5 ± 15.7 preoperatively to 15.9 ± 5.8 at final follow-up (P < .001). Kyphotic deformity was successfully corrected and bony fusion was achieved in all patients. Neurologic function of 7 cases was improved to various degrees.

Modified grade 4 osteotomy, upper disc, and upper one-third to half of pedicle are resected, is an effective treatment option for post-traumatic thoracolumbar kyphosis. However, the long-term clinical effect still needs further studies.
Multiparametric MRI as a Noninvasive Monitoring Tool for Children With Autoimmune Hepatitis
Authors: Janowski Kamil , Shumbayawonda Elizabeth , Dennis Andrea , Kelly Matt , Bachtiar Velicia , DeBrota David , Langford Caitlin , Thomaides‐Brears Helena , Pronicki Maciej , Grajkowska Wieslawa , Wozniak Malgorzata , Pawliszak Piotr , Chełstowska Sylwia , Jurkiewicz Elzbieta , Banerjee Rajarshi , Socha Piotr
Published: September 2020

Objectives:

Autoimmune hepatitis (AIH) is a progressive liver disease managed with corticosteroids and immunosuppression and monitored using a combination of liver biochemistry and histology. However, liver biopsy is invasive with risk of pain and bleeding. The aim of the present study was to investigate the utility of noninvasive imaging with multiparametric magnetic resonance imaging (MRI) (mpMRI) to provide clinically useful information on the presence and extent of hepatic inflammation, potentially guiding immunosuppression.

Methods:

Eighty‐one participants (aged 6–18), 21 healthy and 60 AIH patients, underwent multiparametric MRI to measure fibro‐inflammation with iron‐corrected T1 (cT1) at the Children's Memorial Health Institute in Warsaw alongside other clinical blood tests and liver biopsy at recruitment and after an average of 16‐month follow‐up (range 9–22 months). Correlation analyses were used to investigate the associations between cT1 with blood serum markers and histological scores.

Results:

At recruitment, patients with AIH had a higher cT1 value than healthy controls (P < 0.01). cT1 correlated significantly with key histopathological features of disease. Treatment naïve AIH patients showed evidence of inflammation and heterogeneity across the liver compared to healthy controls.

At follow‐up, cT1 showed utility in monitoring disease regression as most patients showed significantly reduced fibro‐inflammation with treatment (P < 0.0001) over the observational period. Six patients had histological fibrosis and clear fibro‐inflammation on MR despite biochemical remission (normalized aspartate aminotransferase (AST), alanine aminotransferase (ALT), and immunoglobulin G [IgG]).

Conclusions:

Multiparametric MRI can measure disease burden in pediatric AIH and can show changes over time in response to therapy. Active disease can be seen even in biochemical remission in children.
The Significance and Clinical Outcome of Lymphocytic Duodenosis in Children
Authors: Devara Janaki , Alsawas Mouaz , Larson Joseph J. , Mounajjed Taofic , Murray Joseph A. , Absah Imad
Published: September 2020

Background:

Lymphocytic duodenosis (LD) defined as increased intraepithelial lymphocytes >25 intraepithelial lymphocytes (IELs) per 100 epithelial cells with normal villous architecture is associated with many gastrointestinal (GI) disorders. We aim to assess the rate and outcome of LD in children and perform a systematic review.

Method:

We reviewed all children (<18 years) who underwent esophagogastroduodenoscopy (EGD) with duodenal biopsy between January 2000 and June 2019 to identify LD cases and control group. Demographics, clinical, and pathologic information were reviewed and recorded. A systematic review including our findings was performed.

Results:

During the study period 12,744 children underwent an EGD with biopsies. Of those, we identified 426 children with LD (3%) and 474 controls. The median age in years was 10.7 and 12.6 and there were 254 (60%) and 278 (59%) girls in the LD and control group, respectively. The most common presenting symptoms in both groups were abdominal pain (52%), gastroesophageal acid reflux disease (18%), diarrhea (16%), and vomiting (12%). Diarrhea (21% vs 12%, P < 0.001) and constipation (2% vs 0.4%, P = 0.021) were statistically different between the LD and control group, respectively. Median follow‐up (range) is 3.6 (0.0, 190.9) and 3.1 (0.0, 194.2) in the LD and control group, respectively. CD (5% vs 0%, P < 0.001), Crohn disease (9% vs 3%, P = 0.003) and Helicobacter pylori gastritis (3% vs 1%, P = 0.021) were more common in the LD group.

Conclusions:

The Rate of LD in children is similar to reported rate in adults. In the absence of Crohn disease, CD or H. Pylori, LD seems to be a benign and transient histologic finding in children.
Why Are Rates of Reported Chlamydia Changing in the United States? Insights From the National Job Training Program
Authors: Diesel Jill , Kreisel Kristen , R. Learner Emily , Torrone Elizabeth , Peterman Thomas
Published: September 2020

Background

In 2010 to 2017, rates of reported chlamydia decreased among young Black women but increased for White women and all men. Because chlamydia case rates can be influenced by changes in prevalence, screening, and other factors, we compared chlamydia prevalence trends in a sentinel population with national case rate trends to understand potential drivers of case rate trends.

Methods

Chlamydia prevalence was calculated annually among 16- to 24-year-old entrants to the National Job Training Program (NJTP) in 2010 to 2017. An expectation-maximization–based maximum likelihood approach was used to adjust for misclassification due to imperfect test sensitivity and specificity. Models were stratified by sex, age, and race/ethnicity. A statistically significant trend in prevalence was defined as nonoverlapping 95% confidence intervals comparing 2010 and 2017. Trends in chlamydia prevalence were compared with trends in case rates using percentage change over time; relative changes ≥10% were considered meaningful.

Results

Among NJTP entrants in 2010 to 2017, chlamydia prevalence was stable for all Black women, whereas case rates decreased for adolescents (−12%) and were stable for 20- to 24-year-olds (−4%). Among adolescent White women, prevalence was stable, whereas case rates increased (+30%). For White women aged 20 to 24 years, prevalence increased +62% and case rates increased +43%. Trends in prevalence differed from trends in case rates for all subgroups of men.

Conclusions

Prevalence trends in this sentinel population differed from national case rate trends for Black women, White women, and men, suggesting potential decreased screening among Black women aged 16 to 19 years, increased prevalence among White women aged 20 to 24 years, and increased screening among men.
Sound and Air
Authors: Hossain Rubayet , Qadri Usama , Dembowski Nathan , Garcia Angelica , Chen Lei , Cicero Mark X. , Riera Antonio
Published: September 2020

Objectives

Needle decompression is potentially life-saving in cases of tension pneumothorax. Although Advanced Trauma Life Support recommends an 8-cm needle for decompression for adults, no detailed pediatric guidelines exist, specifically regarding needle length or site of decompression.

Methods

Point-of-care ultrasound was used to measure chest wall thickness (CWT), the distance between skin and pleural line, bilaterally at the second intercostal midclavicular line and the fourth intercostal anterior axillary line in children of various ages and sizes. Patients were grouped based on Broselow tape weight categories. Measurements were compared between left versus right sides at the 2 anatomic sites. Interclass correlation coefficients were calculated to assess for interrater reliability.

Results

A convenience sample of 163 patients from our emergency department was enrolled. For patients who fit into Broselow tape categories, CWT at the second intercostal midclavicular line ranged from 1.11 to 1.91 cm and at the fourth intercostal anterior axillary line ranged from 1.13 to 1.92 cm. In patients larger than the largest Broselow category, 77% had a CWT less than the length of a standard 1.25-in (3.175 cm) catheter. There were no significant differences in the measurements of CWT based on laterality nor anatomic site.

Conclusions

The standard 1.25-in (3.175 cm) catheters are sufficient to treat most tension pneumothoraces in pediatric patients.
The Dynamics of Patient Visits to a Public Hospital Pediatric Emergency Department
Authors: Almeida Helena Seabra , Sousa Margarida , Mascarenhas Inês , Russo Ana , Barrento Manuel , Mendes Manuel , Nogueira Paulo , Trigo Ricardo
Published: September 2020

Background

The overcrowding of emergency departments (EDs) is an increasingly relevant public health problem. The main aims of this study were to identify and analyze temporal periodicities of a self-referred pediatric ED (PED), correlate them with meteorological and calendar variables and build a robust forecasting model.

Methods

An 8-year administrative data set (2010–2017) of the daily number of admissions to the PED of a public hospital in Lisbon, Portugal, was used (n = 670,379). A time-series model of the daily number of visits was built, including temporal periodicities, the Portuguese school calendar, and a meteorological comfort index (humidex).

Results

Several temporal cycles were identified: 1 year (peak in January/February related to respiratory infections in younger children and infants), 6 months (peaks in May and October with an increase in the admissions of older children and adolescents with trauma, gastrointestinal infections and atopic symptoms), 4 months (related to annual school vacations), 1 week (lower admission values on Saturday), and half a week (low from Friday to Monday morning). School calendar and humidex were significantly correlated with daily admissions. The model yielded a mean absolute percentage error of 10.7% ± 1.10% when cross-validation was performed for the full data set.

Conclusion

Although PED visits are multifactorial, they may be predicted and explained by a relatively small number of variables. Such a model may be easily reproduced in different settings and represents a relevant tool to improve quality in EDs through correctly adapting human resources to ED demand.
Urgent Care Centers Delay Emergent Surgical Care Based on Patient Insurance Status in The United States
Authors: Hsiang Walter R. , Wiznia Daniel , Yousman Laurie , Najem Michael , Mosier-Mills Alison , Jin Grace , Jain Siddharth , Khunte Akshay , Davis Kimberly A. , Forman Howard P. , Schuster Kevin M.
Published: September 2020

Objective:

Patients may call urgent care centers (UCCs) with urgent surgical conditions but may not be properly referred to a higher level of care. This study aims to characterize how UCCs manage Medicaid and privately insured patients who present with an emergent condition.

Methods:

Using a standardized script, we called 1245 randomly selected UCCs in 50 states on 2 occasions. Investigators posed as either a Medicaid or a privately-insured patient with symptoms of an incarcerated inguinal hernia. Rates of direct emergency department (ED) referral were compared between insurance types.

Results:

A total of 1223 (98.2%) UCCs accepted private insurance and 981 (78.8%) accepted Medicaid. At the 971 (78.0%) UCCs that accepted both insurance types, direct-to-ED referral rates for private and Medicaid patients were 27.9% and 33.8%, respectively. Medicaid patients were significantly more likely than private patients to be referred to the ED [odds ratio (OR) 1.32, 95% confidence interval (CI) 1.09–1.60]. Private patients who were triaged by a clinician compared to nonclinician staff were over 6 times more likely to be referred to the ED (OR 6.46, 95% CI 4.63–9.01). Medicaid patients were nearly 9 times more likely to have an ED referral when triaged by a clinician (OR 8.72, 95% CI 6.19–12.29).

Conclusions:

Only one-third of UCCs across the United States referred an apparent emergent surgical case to the ED, potentially delaying care. Medicaid patients were more likely to be referred directly to the ED versus privately insured patients. All patients triaged by clinicians were significantly more likely to be referred to the ED; however, the disparity between private and Medicaid patients remained.
Socioeconomic Factors and Intensive Care Unit-Related Cognitive Impairment
Authors: Haddad Diane N. , Mart Matthew F. , Wang Li , Lindsell Christopher J. , Raman Rameela , Nordness Mina F. , Sharp Kenneth W. , Pandharipande Pratik P. , Girard Timothy D. , Ely E. Wesley , Patel Mayur B.
Published: September 2020

Objective:

We aimed to identify socioeconomic and clinical risk factors for post-intensive care unit (ICU)-related long-term cognitive impairment (LTCI).

Summary Background Data:

After delirium during ICU stay, LTCI has been increasingly recognized, but without attention to socioeconomic factors.

Methods:

We enrolled a prospective, multicenter cohort of ICU survivors with shock or respiratory failure from surgical and medical ICUs across 5 civilian and Veteran Affairs (VA) hospitals from 2010 to 2016. Our primary outcome was LTCI at 3- and 12 months post-hospital discharge defined by the Repeatable Battery for Assessment of Neuropsychological Symptoms (RBANS) global score. Covariates adjusted using multivariable linear regression included age, sex, race, AHRQ socioeconomic index, Charlson comorbidity, Framingham stroke risk, Sequential Organ Failure Assessment, duration of coma, delirium, hypoxemia, sepsis, education level, hospital type, insurance status, discharge disposition, and ICU drug exposures.

Results:

Of 1040 patients, 71% experienced delirium, and 47% and 41% of survivors had RBANS scores >1 standard deviation below normal at 3- and 12 months, respectively. Adjusted analysis indicated that delirium, non-White race, lower education, and civilian hospitals (as opposed to VA), were associated with at least a half standard deviation lower RBANS scores at 3- and 12 months (P ≤ 0.03). Sex, AHRQ socioeconomic index, insurance status, and discharge disposition were not associated with RBANS scores.

Conclusions:

Socioeconomic and clinical risk factors, such as race, education, hospital type, and delirium duration, were linked to worse PICS ICU-related, LTCI. Further efforts may focus on improved identification of higher-risk groups to promote survivorship through emerging improvements in cognitive rehabilitation.
Whole Blood is Superior to Component Transfusion for Injured Children
Authors: Leeper Christine M. , Yazer Mark H. , Triulzi Darrell J. , Neal Matthew D. , Gaines Barbara A.
Published: September 2020

Objective:

To compare a propensity-matched cohort of injured children receiving conventional blood component transfusion to injured children receiving low-titer group O negative whole blood.

Summary of Background Data:

Transfusion of whole blood in pediatric trauma patients is feasible and safe. Effectiveness has not been evaluated.

Methods:

Injured children ≥1 years old can receive up to 40 mL/kg of cold-stored, uncrossmatched whole blood during initial hemostatic resuscitation. Whole blood recipients (2016–2019) were compared to a propensity-matched cohort who received at least 1 uncrossmatched red blood cell unit in the trauma bay (2013–2016). Cohorts were matched for age, hypotension, traumatic brain injury, injury mechanism, and need for emergent surgery. Outcomes included time to resolution of base deficit, product volumes transfused, and INR after resuscitation.

Results:

Twenty-eight children who received whole blood were matched to 28 children who received components. The whole blood group had faster time to resolution of base deficit [median (IQR) 2 (1–2.5) hours vs 6 (2–24) hours, respectively; P < 0.001]. The post-transfusion INR was decreased in whole blood vs component cohort [median (IQR) 1.4 (1.3–1.5) vs 1.6 (1.4–2.2); P = 0.01]. Lower plasma volumes [median (IQR) = 5 (0–15) mL/kg vs 11 (5–35) mL/kg; P = 0.04] and lower platelet volumes [median (IQR) = 0 (0–2) vs 3 (0–8); P = 0.03] were administered to the whole blood group versus component group. Other clinical variables (in-hospital death, hospital length of stay, intensive care unit length of stay, and ventilator days) did not differ between groups.

Conclusions:

Compared to component transfusion, whole blood transfusion results in faster resolution of shock, lower post-transfusion INR, and decreased component product transfusion. Larger cohorts are required to support these findings.
Multiplexed Plasma Immune Mediator Signatures Can Differentiate Sepsis From NonInfective SIRS
Authors: Cahill Laura A. , Joughin Brian A. , Kwon Woon Yong , Itagaki Kiyoshi , Kirk Charlotte H. , Shapiro Nathan I. , Otterbein Leo E. , Yaffe Michael B. , Lederer James A. , Hauser Carl J.
Published: September 2020

Objectives:

Sepsis and sterile both release “danger signals" that induce the systemic inflammatory response syndrome (SIRS). So differentiating infection from SIRS can be challenging. Precision diagnostic assays could limit unnecessary antibiotic use, improving outcomes.

Methods:

After surveying human leukocyte cytokine production responses to sterile damage-associated molecular patterns (DAMPs), bacterial pathogen-associated molecular patterns, and bacteria we created a multiplex assay for 31 cytokines. We then studied plasma from patients with bacteremia, septic shock, “severe sepsis,” or trauma (ISS ≥15 with circulating DAMPs) as well as controls. Infections were adjudicated based on post-hospitalization review. Plasma was studied in infection and injury using univariate and multivariate means to determine how such multiplex assays could best distinguish infective from noninfective SIRS.

Results:

Infected patients had high plasma interleukin (IL)-6, IL-1α, and triggering receptor expressed on myeloid cells-1 (TREM-1) compared to controls [false discovery rates (FDR) <0.01, <0.01, <0.0001]. Conversely, injury suppressed many mediators including MDC (FDR <0.0001), TREM-1 (FDR <0.001), IP-10 (FDR <0.01), MCP-3 (FDR <0.05), FLT3L (FDR <0.05), Tweak, (FDR <0.05), GRO-α (FDR <0.05), and ENA-78 (FDR <0.05). In univariate studies, analyte overlap between clinical groups prevented clinical relevance. Multivariate models discriminated injury and infection much better, with the 2-group random-forest model classifying 11/11 injury and 28/29 infection patients correctly in out-of-bag validation.

Conclusions:

Circulating cytokines in traumatic SIRS differ markedly from those in health or sepsis. Variability limits the accuracy of single-mediator assays but machine learning based on multiplexed plasma assays revealed distinct patterns in sepsis- and injury-related SIRS. Defining biomarker release patterns that distinguish specific SIRS populations might allow decreased antibiotic use in those clinical situations. Large prospective studies are needed to validate and operationalize this approach.
Adhesion of Staphylococcus aureus to epithelial cells: an in vitro approach to study interactions within the nasal microbiota
Authors: Ménard Guillaume , Bonnaure-Mallet Martine , Donnio Pierre-Yves
Published: September 2020

Introduction.

Staphylococcus aureus

is a skin and mucous commensal bacterium of warm-blooded animals. In humans, the nose is the main ecological niche of

S. aureus

, and nasal carriage is a risk factor for developing an endogenous infection.

S. aureus

nasal colonization is a multifactorial process, involving inter-species interactions among the nasal microbiota.

Aims. The objectives of this study were to characterize the microbiota of carriers and non-carriers of

S. aureus

and to demonstrate the importance of inter-species relationships in the adhesion of

S. aureus

, a key step in nasal colonization.

Methodology. First, we characterized the nasal microbiota from 30

S. aureus

carriers and non-carriers by a culturomic approach. We then evaluated the adhesion of

S. aureus

, first alone and then along with other bacteria of the nasal microbiota. To do that, we used an in vitro model to measure the interactions among bacteria in the presence of epithelial cells.

Results. Analysis of the nasal microbiota of the carriers and non-carriers of

S. aureus

made it possible to observe that each microbiota has specific features in terms of composition. However, this composition differs significantly between carriers and non-carriers mainly through two bacterial groups: coagulase-negative staphylococci and corynebacteria. In a second part, adhesion of

S. aureus

to epithelial cells showed competition between

S. aureus

and these bacteria, suggesting a limitation of nasal colonization by

S. aureus

.

Conclusion. These findings demonstrate the existence of a negative correlation between

S. aureus

and other species which inhibits adhesion and could limit nasal colonization.
Synergistic effects of natural products and commercial antibiotics—A mini–review 2010–2015
Authors: Nitsch-Velásquez Lucía
Published: September 2020

1

Context

The ‘antimicrobial resistant era’ requires advances in the approaches and technologies to find new treatments. The enhancement of the antimicrobial activity of commercially available drugs (CADs) by natural products (NPs) has successful mixtures (e.g., clavulanic acid and amoxicillin).

Objective

To systematically review reports of synergistic effects of CADs and NPs against opportunistic microbial strains from 2010 to April 2016.

Methods

The databases and search engines PubMed, Medline, Scifinder, Scopus, ScienceDirect, Scholar Google were systematically searched. Among the keywords utilized were: synergistic effects natural products and antibioitcs, botanicals and antibiotics bioassays, plant extracts interaction with antibioitics and antibiotic adjuvant bioassays. Only synergistic results were tabulated and analyzed according to CADs, NPs and strains.

Results

A set of 76 studies that reported in vitro synergistic effects of CADs and NPs against gram–positive or gram–negative bacteria or fungi opportunistic strains was found. From the 60 reports on antibacterial adjuvants, the most frequent designs involved beta–lactamics or aminoglycosides against Methicillin Resistant Staphylococcus aureus. The assayed NPs encompassed extracts or fractions from 22 different species distributed worldwide (45% extracted with non–polar solvents) and 33 purified compounds (flavonoids, other polyphenols and alkaloids).

Conclusions

NPs as potential drug hits for antimicrobial adjuvants had been found and should continue in the drug discovery pipeline. The field certainly would benefit of advances in purification technologies, especially for polar extracts and bioassay platforms.
Detergent wash improves vaccinated lymph node handling ex vivo
Authors: Ball Alexander G. , Belanger Maura C. , Pompano Rebecca R.
Published: September 2020

Lymph nodes (LNs) are essential secondary immune organs where the adaptive immune response is generated against most infections and vaccines. We recently described the use of live ex vivo LN slices to study the dynamics of adaptive immunity. However, when working with reactive lymph nodes from vaccinated animals, the tissues frequently became dislodged from the supportive agarose matrix during slicing, leading to damage that prevented downstream analysis. Because reactive lymph nodes expand into the surrounding adipose tissue, we hypothesized that dislodging was a result of excess lipids on the collagen capsule of the LN, and that a brief wash with a mild detergent would improve LN interaction with the agarose without damaging tissue viability or function. Therefore, we tested the use of digitonin on improving slicing of vaccinated LNs. Prior to embedding, LNs were quickly dipped into a digitonin solution and washed in saline. Lipid droplets were visibly removed by this procedure. A digitonin wash step prior to slicing significantly reduced the loss of LN during slicing from 13 - 75 % to 0 - 25 %, without substantial impact on viability. Capture of fluorescent microparticles, uptake and processing of protein antigen, and cytokine secretion in response to a vaccine adjuvant, R848, were all unaffected by the detergent wash. This novel approach will enable ex vivo analysis of the generation of adaptive immune response in LNs in response to vaccinations and other immunotherapies.
The Impact of COVID-19 Pandemic on The Preventive Services in Qatar
Authors: Al-Kuwari Mohamed Ghaith , Abdulmalik Mariam Ali , Al-Mudahka Hamad Rashid , Bakri Ahmad Haj , Al-Baker Wadha Ahmed , Abushaikha Shaikha Sami , Kandy Mujeeb Chettiyam , Gibb John
Published: September 2020

Background

In March 2020, Qatar started reporting increased numbers of COVID-19 cases. At that stage, containment measures were put in place. The health authority in Qatar developed an emergency action plan to respond to the outbreak with the Primary Health Care as the main component of that response and suspended all non-urgent services including preventive health services. The aim of the retrospective analysis to measure the Impact of COVID 19 on the preventive services provided in Qatar.

Methods

A retrospective data analysis was conducted for all the preventive services utilization volume across the 27 PHCC health centers from the 1st of January 2017 to the 31st of July 2020.

Results

With 17,012 no-show appointments, well-baby and Immunization services utilization demonstrated a reduction of 40% in May and started to come back to volumes higher than expected in June. The number of cancelled appointments for breast cancer and colorectal cancer screening programs were 3,481 and 5,854 respectively. The expected volumes demand has dropped by 100% in comparison to 2017 demand. Wellness services only met 20% of its projected utilization in April, however, the services picked up in June.

Conclusion

These findings will guide the public health policymakers to understand the effects COVID-19 on preventive services and the risk of having an increased number of outbreaks for childhood communicable disease, cancer cases with delayed diagnosis due to the screening services suspension. In addition, the plan will address the increased number of sedately behavior due to the service’s reduced utilization of wellness services.
The relationship between cognitive function and sleep duration: a Mendelian randomisation study
Authors: Salzmann Antoine , Chaturvedi Nish , Garfield Victoria
Published: September 2020

Structured abstract

Importance

Sleep duration is associated with cognitive function, with Mendelian randomisation evidence supporting a relationship in this direction. However, whether cognitive function may also precede problematic sleep duration remains unclear.

Objective

To assess whether reaction time and visual memory are causally associated with sleep duration.

Design

Summary-level Mendelian randomisation design between visual memory (30 SNPs), reaction time (44 SNPs), and self-reported and objective sleep duration Setting: Population-based study.

Participants

Individuals from the UK Biobank, who were included in genome-wide association studies for our exposures and outcomes, aged 40-69y at baseline (mean 56y), 54% female and self-reported sleep was 7.2 hours.

Exposures

Visual memory, reactiontime

Main outcomes

self-reported and objective sleep duration

Results

Mendelian randomisation results showed that worse performance on the visual memory task was associated with longer (ß=0.09, 95% CI=0.02;0.17), while slower reaction time was associated with shorter (ß=-0.15, 95% CI=-0.29;-0.01), objective sleep duration. Sensitivity analyses revealed no issues with horizontal pleiotropy (MR-Egger intercept p-value <0.05). No association was observed between either cognitive measure and self-reported sleep duration.

Conclusions and relevance

These results suggest a potential causative relationship between reaction time and objective sleep duration, where worse visual memory is associated with longer, and worse reaction time with shorter objective sleep duration. This study furthers our understanding of the relationship between brain health and sleep duration and sheds light on the causal nature of these associations.

Key points

Question

Is genetically predicted sleep duration (accelerometer-derived and self-reported) associated with cognitive function outcomes?

Findings

In this summary-level Mendelian randomisation study, worse visual memory was associated with longer, whereas worse reaction time was associated with shorter, objective sleep duration. No associations were observed between cognitive measures and self-reported sleep duration.

Meaning

These findings suggest a causal association between cognition and objective sleep duration measures, expanding our understanding of the relationship between cognition and sleep.
Association of nocebo hyperalgesia and basic somatosensory characteristics in a large cohort
Authors: Feldhaus Mari Hanna , Horing Björn , Sprenger Christian , Büchel Christian
Published: September 2020

Medical outcomes are strongly affected by placebo and nocebo effects. Prediction of who responds to such expectation effects has proven to be challenging. Most recent approaches to prediction have focused on placebo effects in the context of previous treatment experiences and expectancies, or personality traits. However, a recent model has suggested that basic somatosensory characteristics play an important role in expectation responses. Consequently, this study investigated not only the role of psychological variables, but also of basic somatosensory characteristics. In this study, 624 participants underwent a placebo and nocebo heat pain paradigm. Additionally, individual psychological and somatosensory characteristics were assessed. While no significant correlations for placebo responses were identified, nocebo responses were correlated with personality traits (e.g. neuroticism) and somatosensory characteristics (e.g. thermal pain threshold). Importantly, the correlations between somatosensory characteristics and nocebo responses were among the strongest. This study shows that apart from personality traits, basic somatosensory characteristics play an important role in individual nocebo responses, in agreement with the novel idea that nocebo responses result from the integration of top-down expectation and bottom-up sensory information.
Frequency and Management of Drug and Chemical Poisoning among Children Attending an Emergency Department in a Single Hospital in Saudi Arabia
Authors: Tobaiqy Mansour , Asiri Bandar A. , Sholan Ahmed H. , Alzahrani Yahya A. , Alkatheeri Ayed A. , Mahha Ahmed M. , Alzahrani Shamsia
Published: September 2020

Background

Unintentional poisoning is one of the common medical emergencies in children that leads to morbidity and mortality. Medications and chemical agents play a major role in these adverse events resulting in social, economic, and health consequences.

Aims of the study

The study aimed to evaluate the frequency and management of poisoning among children attending the emergency room at East Jeddah Hospital, Jeddah city, Saudi Arabia.

Methods

This study was a retrospective chart review of all acute pediatric poisoning incidences in children (0-16 years of age) from October-21-2016 to March-03-2020 who were admitted to the emergency department of East Jeddah Hospital, Jeddah city, Saudi Arabia. Data was analyzed via SPSS software.

Results

A total of 69 incidences of acute poisoning were admitted to the emergency room at East Jeddah Hospital; males were 55.1 %. Most children were under 5 years of age (59.4%). Unintentional poisoning occurred among 56.5% of observed cases of which 52.2% occurred in children younger than 5 years; 7.20% (5) patients were 12 to 16 years of age and had deliberate self-poisoning. The association between type of poisoning and age groups was statistically significant (Chi-square = 28.5057, p = 0.0001). Most incidences occurred at home (92.8%). Medicines were the most common cause of poisoning (73.9%). An excessive dose of prescribed medicine poisoning accidents was reported in 10.1% cases. Analgesics such as paracetamol were the most documented medication associated with poisoning (39.1%) followed by anticonvulsants and other central nervous system acting medicines (18.8 %). The most common route of poisoning was oral administration (81.2%). One mortality case was documented due to poisoning.

Conclusion

A total of 69 incidences of acute poisoning in children occurred in a single hospital over 3 years. Most incidents were unintentional and occurred in children younger than 5 years of age. Medicines were the most common cause of poisoning. Analgesics such as paracetamol were the most common documented medicine associated with poisoning.
Chromosome-level genome assembly of a benthic associated Syngnathiformes species: the common dragonet,Callionymus lyra
Authors: Winter Sven , Prost Stefan , de Raad Jordi , Coimbra Raphael T. F. , Wolf Magnus , Nebenführ Marcel , Held Annika , Kurzawe Melina , Papapostolou Ramona , Tessien Jade , Bludau Julian , Kelch Andreas , Gronefeld Sarah , Schöneberg Yannis , Zeitz Christian , Zapf Konstantin , Prochotta David , Murphy Maximilian , Sheffer Monica M. , Sonnewald Moritz , Nilsson Maria A. , Janke Axel
Published: September 2020

Background

The common dragonet,Callionymus lyra, is one of threeCallionymusspecies inhabiting the North Sea. All three species show strong sexual dimorphism. The males show strong morphological differentiation, e.g., species-specific colouration and size relations, while the females of different species have few distinguishing characters.Callionymusbelongs to the ‘benthic associated clade’ of the order Syngnathiformes. The ‘benthic associated clade’ so far is not represented by genome data and serves as an important outgroup to understand the morphological transformation in ‘long-snouted’ syngnatiforms such as seahorses and pipefishes.

Findings

Here, we present the chromosome-level genome assembly ofC. lyra. We applied Oxford Nanopore Technologies’ long-read sequencing, short-read DNBseq, and proximity-ligation-based scaffolding to generate a high-quality genome assembly. The resulting assembly has a contig N50 of 2.2 Mbp, a scaffold N50 of 26.7 Mbp. The total assembly length is 568.7 Mbp, of which over 538 Mbp were scaffolded into 19 chromosome-length scaffolds. The identification of 94.5% of complete BUSCO genes indicates high assembly completeness. Additionally, we sequenced and assembled a multi-tissue transcriptome with a total length of 255.5 Mbp that was used to aid the annotation of the genome assembly. The annotation resulted in 19,849 annotated transcripts and identified a repeat content of 27.66%.

Conclusions

The chromosome-level assembly ofC. lyraprovides a high-quality reference genome for future population genomic, phylogenomic, and phylogeographic analyses.
Integration of A Nitrate-Related Signaling Pathway in Rhizobia-Induced Responses During Interactions with Non-Legume Host Arabidopsis thaliana
Authors: Schenk Sebastian T. , Lichtenberg Elisabeth , Keller Jean , Delaux Pierre-Marc , Ott Thomas
Published: September 2020

Nitrogen (N) is an essential macronutrient and a key cellular messenger. Plants have evolved refined molecular systems to sense the cellular nitrogen status. Exemplified by the root nodule symbiosis between legumes and symbiotic rhizobia, where external nitrate availability inhibits the interaction. However, nitrate also functions as a metabolic messenger, resulting in nitrate signaling cascades which intensively cross-talk with other physiological pathways. NIN (NODULE INCEPTION)-LIKE PROTEINS (NLPs) are key players in nitrate signaling and regulate nitrate-dependent transcription. Nevertheless, the coordinated interplay between nitrate signaling pathways and rhizobacteria-induced responses remains to be elucidated. In our study, we investigate rhizobia-induced changes in the root system architecture of the non-legume host Arabidopsis in dependence of different nitrate conditions. We demonstrate that rhizobia induce lateral root growth, and increase root hair length and density in a nitrate-dependent manner. These processes are regulated by AtNLP4 and AtNLP5 as well as nitrate transceptor NRT1.1, as the corresponding mutants fail to respond to rhizobia. On a cellular level,NLP4andNLP5control a rhizobia-induced decrease in cell elongation rates, while additional cell divisions occurred independent ofNLP4. In summary, our data suggest that root morphological responses to rhizobia, dependent on a nutritional signaling pathway that is evolutionary related to regulatory circuits described in legumes.
The Temporal Dynamics of Opportunity Costs: A Normative Account of Cognitive Fatigue and Boredom
Authors: Agrawal Mayank , Mattar Marcelo G. , Cohen Jonathan D. , Daw Nathaniel D.
Published: September 2020

Cognitive fatigue and boredom are two phenomenological states that reflect overt task disengagement. In this paper, we present a rational analysis of the temporal structure of controlled behavior, which provides a formal account of these phenomena. We suggest that in controlling behavior, the brain faces competing behavioral and computational imperatives, and must balance them by tracking their opportunity costs over time. We use this analysis to flesh out previous suggestions that feelings associated with subjective effort, like cognitive fatigue and boredom, are the phenomenological counterparts of these opportunity cost measures, instead of reflecting the depletion of resources as has often been assumed. Specifically, we propose that both fatigue and boredom reflect the competing value of particular options that require foregoing immediate reward but can improve future performance: Fatigue reflects the value of offline computation (internal to the organism) to improve future decisions, while boredom signals the value of exploration (external in the world). We demonstrate that these accounts provide a mechanistically explicit and parsimonious account for a wide array of findings related to cognitive control, integrating and reimagining them under a single, formally rigorous framework.
Barriers to gene flow play an important role in miantaining reproductive isolation between two closely relatedPopulus(Salicaceae) species
Authors: Tian Yang , Liu Shuyu , Ingvarsson Pär K. , Zhao Dandan , Wang Li , Abuduhamiti Baoerjiang , Wu Zhiqiang , Zhang Jianguo , Wang Zhaoshan
Published: September 2020

In most species, natural selection plays a key role in genomic heterogeneous divergence. Additionally, barriers to gene flow, such as chromosomal rearrangements or gene incompatibilities, can cause genome heterogeneity. We used genome-wide re-sequencing data from 27Populus albaand 28P. adenopodaindividuals to explore the causes of genomic heterogeneous differentiation in these two closely related species. In highly differentiated regions, neutrality tests (Tajima’s D and Fay & Wu’s H) revealed no difference while the absolute divergence (dxy) were significantly higher than genome background, which indicates that natural selection did not play a major role but barriers to gene flow play an important role in generating genomic heterogeneous divergence and reproductive isolation. The two species diverged ∼5-10 million years ago (Mya), when the Qinghai-Tibet Plateau reached a certain height and the inland climate of the Asian continent became arid. We further found some genes that are related to reproduction.
NEON Crowns: a remote sensing derived dataset of 100 million individual tree crowns
Authors: Weinstein Ben. G. , Marconi Sergio , Bohlman Stephanie , Zare Alina , Singh Aditya , Graves Sarah J. , White Ethan
Published: September 2020

Forests provide essential biodiversity, ecosystem and economic services. Information on individual trees is important for understanding the state of forest ecosystems but obtaining individual-level data at broad scales is challenging due to the costs and logistics of data collection. While advances in remote sensing techniques allow surveys of individual trees at unprecedented extents, there remain significant technical and computational challenges in turning sensor data into tangible information. Using deep learning methods, we produced an open-source dataset of individual-level crown estimates for 100 million trees at 37 sites across the United States surveyed by the National Ecological Observatory Network’s Airborne Observation Platform. Each canopy tree crown is represented by a rectangular bounding box and includes information on the height, crown area, and spatial location of the tree. Tree crowns identified using this technique correspond well with hand-labeled crowns, exhibiting both high levels of overlap and good correspondence in height estimates. These data have the potential to drive significant expansion of individual-level research on trees by facilitating both regional analyses at scales of ~10,000 ha and cross-region comparisons encompassing forest types from most of the United States.
Distinguishing between interaction and dispersion effects in the analysis of gene-environment interaction
Authors: Domingue Benjamin W. , Kanopka Klint , Mallard Travis T. , Trejo Sam , Tucker-Drob Elliot M.
Published: September 2020

Genotype-by-environment interaction (GxE) occurs when the size of a genetic effect varies systematically across levels of the environment and when the size of an environmental effect varies systematically across levels of the genotype. However, total variance in the phenotype may shift as a function of the moderator irrespective of its etiology such that theproportionaleffect of the predictor is constant. We expand the traditional GxE regression model to directly account for heteroscedasticity associated with both the genotype and the measured environment. We then derive a test statistic,ξ, for inferring whether GxE can be attributed to an effect of the moderator on the dispersion of the phenotype. We apply this method to identify genotype-by-birth year interactions for Body Mass Index (BMI) that are distinguishable from general secular increases in the variance of BMI or associations of the genetic predictors (both PGS and individual loci) with BMI variance. We provide software for analyzing such models.