bluuebunny/crossref_metadata_2025 huggingface dataset:
Arterial hypertension and cerebral hemodynamics: impact of head-down tilt on cerebral blood flow (arterial spin-labeling-MRI) in healthy and hypertensive patients
Authors: Seiller Ian , Pavilla Aude , Ognard Julien , Ozier-Lafontaine Nathalie , Colombani Sylvie , Cepeda Ibarra Yamilet , Mejdoubi Mehdi
Published: December 2020

Objective:

Hypertension affects cerebrovascular autoregulation and increases the risk of cerebrovascular events and dementia. Notably, it is associated with cerebrovascular remodeling and lower resting cerebral blood flow (CBF). We wanted to determine, using arterial spin-labeling-MRI, the impact of a head-down tilt (HDT) dynamic maneuver on CBF in hypertensive patients.

Methods:

The current prospective study measured 36 patients’ CBFs (18 normotensive individuals; 18 hypertensive patients) on 1.5T arterial spin-labeling-MRI in the supine position and after 4 min at −15° HDT. We reconstructed CBF maps of left and right subcortical nuclear gray matter, cortical gray matter and white matter (16 structures) to explore cerebrovascular autoregulation modification under dynamic conditions.

Results:

Normotensive and hypertensive participants had no significant CBF differences in the supine position. After HDT, CBF mean variations (CBF-mVs) across all structures declined (mean −5.8%) for the whole population (n = 36), with −6.6 and −7.6% decreases, respectively, in white matter and gray matter (P < 0.001). Left and right accumbens nuclei had the largest changes (−9.6 and −9.2%, respectively; P < 0.001). No CBF-mV difference (0/16) was found in hypertensive patients after HDT, whereas normotensive participants’ CBF-mVs changed significantly in four structures (left and right accumbens, putamen and left caudate nucleus) and gray matter. Hypertensive patients exhibited fewer CBF-mVs in left caudate nuclei (P = 0.039) and cortical gray matter (P = 0.013). Among hypertensive patients, people with diabetes had smaller CBF-mVs than people without diabetes.

Conclusion:

Our results highlight the significantly different CBF reactions to HDT of normotensive and hypertensive participants. They support the hypothesis that hypertension is responsible for deficient cerebrovascular autoregulation.
PREVALENCE OF VITREOUS CORTEX REMNANTS IN EYES WITH PRIMARY RHEGMATOGENOUS RETINAL DETACHMENT UNDERGOING VITRECTOMY
Authors: Assi Alexandre , Khoueir Ziad
Published: December 2020

Background/Purpose:

To evaluate the prevalence and extent of vitreous cortex remnants (VCR) on the surface of the retina in eyes with primary rhegmatogenous retinal detachment (RRD) and posterior vitreous detachment.

Methods:

Triamcinolone acetonide was injected in the vitreous cavity of 100 consecutive cases of acute primary RRD undergoing pars plana vitrectomy. A multivariate regression analysis was performed to determine any association between the presence and pattern of stained VCR on the surface of the retina and the following variables: age, diabetes, axial length, phakic status, extent of RRD, and macular status.

Results:

Vitreous cortex remnants were found in 42 eyes. These were focal in eight eyes and diffuse in 34 eyes. Age was the only strong and independent risk factor associated with the presence of VCR (P= 0.0019). Age (P< 0.0001), axial length (P= 0.0037), and phakia (P= 0.01) were independent risk factors associated with the diffuse pattern. Neither diabetes, extent of RRD, nor macular status were significant risk factors for the presence or extent of VCR.

Conclusion:

Older patients with primary RRD and posterior vitreous detachment seem to be at a higher risk of having diffuse VCR. Further studies are needed to investigate the relevance of VCR in the pathogenesis, progression and treatment of RD.
How Perceived Structural Racism and Discrimination and Medical Mistrust in the Health System Influences Participation in HIV Health Services for Black Women Living in the United States South: A Qualitative, Descriptive Study
Authors: Randolph Schenita D. , Golin Carol , Welgus Hayley , Lightfoot Alexandra F. , Harding Caressa J. , Riggins Linda F.
Published: December 2020

There are racial and geographic disparities for HIV in the United States; Black women have nearly 20 times the risk of White women in being infected with HIV, and lifetime HIV risk is greatest for people living in the southern United States. These disparities, layered with the structural racism and discrimination that is more prominent in the south, is a public health issue. The purpose of this article is to share Black women's perspectives of how perceived structural racism and discrimination, and medical mistrust in the health care system contribute to their participation in health services. In this formative study, we conducted seven focus groups among women living in 10 low-income housing communities. Results indicate that there are barriers to the utilization of health services that are grounded in personal experiences and historical mistrust for the health care system. Understanding these barriers is critical to combating the HIV epidemic for this population.
Screening Strategies for Deafness Genes and Functional Outcomes in Cochlear Implant Patients
Authors: Nisenbaum Eric , Prentiss Sandra , Yan Denise , Nourbakhsh Aida , Smeal Molly , Holcomb Meredith , Cejas Ivette , Telischi Fred , Liu Xue Zhong
Published: December 2020

Objectives:

To review the current state of knowledge about the influence of specific genetic mutations that cause sensorineural hearing loss (SNHL) on cochlear implant (CI) functional outcomes, and how this knowledge may be integrated into clinical practice. A multistep and sequential population-based genetic algorithm suitable for the identification of congenital SNHL mutations before CI placement is also examined.

Data Sources, Study Selection:

A review was performed of the English literature from 2000 to 2019 using PubMed regarding the influence of specific mutations on CI outcomes and the use of next-generation sequencing for genetic screening of CI patients.

Conclusion:

CI is an effective habilitation option for patients with severe-profound congenital SNHL. However, it is well known that CI outcomes show substantial inter-patient variation. Recent advances in genetic studies have improved our understanding of genotype–phenotype relationships for many of the mutations underlying congenital SNHL, and have explored how these relationships may account for some of the variance seen in CI performance outcomes. A sequential genetic screening strategy utilizing next-generation sequencing-based population-specific gene panels may allow for more efficient mutation identification before CI placement. Understanding the relationships between specific mutations and CI outcomes along with integrating routine comprehensive genetic testing into pre-CI evaluations will allow for more effective patient counseling and open the door for the development of mutation-specific treatment strategies.
Development and Validation of the Spanish AzBio Sentence Corpus
Authors: Rivas Alejandro , Perkins Elizabeth , Rivas Adriana , Rincon Luz Adriana , Litvak Leo , Spahr Tony , Dorman Michael , Kessler David , Gifford René
Published: December 2020

Objective:

To create and validate a Spanish sentence test for evaluation of speech understanding of Spanish-speaking listeners with hearing loss or cochlear implants (CI).

Study Design:

Two thousand sentences were recorded from two male and two female speakers. The average intelligibility of each sentence was estimated as the mean score achieved by five listeners presented with a five-channel cochlear implant simulation. The mean scores of each sentence were used to construct 42 lists of 20 sentences with similar mean scores. List equivalency was then validated by presenting all lists to 10 CI users and in a 2-list comparison in a clinical setting to 38 CI patients.

Setting:

Tertiary referral center.

Patients:

Normal-hearing listeners (n = 5), CI users in a research study (n = 10), and CI patients (n = 38) in routine clinical follow-up.

Intervention:

Multiple sentence lists from a newly minted speech perception test.

Main Outcome Measures:

List intelligibility and equivalence across sentence lists.

Results:

Forty-two lists of sentences were equivalent when all lists were presented in random order to 10 adult CI recipients. The variability of scores observed on lists presented to the same listener in the same condition was captured using a binomial distribution model based on a 40-item list for 38 adult implant recipients.

Conclusion:

The Spanish AzBio Sentence Test includes 42 lists of 20 sentences. These sentences are roughly equivalent in terms of overall difficulty and confidence limits have been provided to assess the significance of variability in list scores observed within or across conditions. These materials will be of benefit when assessing native Spanish speakers in both research and clinical settings.
Upregulation of tissue long noncoding RNA X inactive specific transcript predicts poor postoperative survival in patients with non-small cell lung cancer
Authors: Fang Hengxiao , Yang Liushan , Fan Yue , Mo Chunrong , Luo Lei , Liang Daying , Jiang Yi
Published: December 2020

X inactive specific transcript (XIST) is a novel long noncoding RNA (lncRNA) which has been reported to be frequently upregulated in various human cancer types and to function as an oncogene. It has been reported that the expression of lncRNA XIST was upregulated in non-small cell lung cancer (NSCLC). In the present study, we aimed to investigate the clinical significance and prognostic value of XIST in patients with NSCLC.

A total of 156 pairs of NSCLC and corresponding adjacent normal lung tissue samples were obtained from NSCLC patients who had undergone surgery from July 2014 to March 2019. The Student's t test was used in different treated groups for statistical analysis. The association between XIST expression and clinicopathological features of NSCLC patients was evaluated using the chi-squared test. Survival curves were plotted using Kaplan-Meier method and compared by log-rank test.

The expression of XIST was significantly higher in NSCLC samples compared to non-cancerous samples (P < .001). Statistically significant correlations were observed between high tissue XIST expression level and lymph node metastasis (P = .036) and high Tumor Node Metastasis (TNM) stage (P = .002). The log-rank test indicated that patients with increased XIST expression experienced poor overall survival (P = .006). Multivariate Cox regression analysis showed that XIST expression level (hazard ratio = 2.645, 95% confidence interval: 1.672–7.393, P = .029) was an independent factors in predicting the overall survival of NSCLC patients.

The present study found that XIST expression level was significantly associated with advanced pathological stage and high TNM stage in NSCLC. Furthermore, upregulation of tissue lncRNA XIST predicts poor postoperative survival in patients with NSCLC.
The APLNR gene polymorphism rs7119375 is associated with an increased risk of development of essential hypertension in the Chinese population
Authors: Yoshikawa Masahiro , Asaba Kensuke , Nakayama Tomohiro
Published: December 2020

Hypertension (HT) has recently been defined as a systolic blood pressure (BP) of ≥130 mm Hg and/or a diastolic BP of ≥80 mm Hg. It is important to further understand the pathophysiology of essential HT as its proportion is larger among most of the diagnosed HT cases. The apelin and apelin receptor (APLNR) are known to play roles in regulating BP, but the putative associations of single nucleotide polymorphisms in the APLNR gene with the risk of development of essential HT have not yet been fully investigated. Herein, we conducted a meta-analysis to investigate the relationship between single nucleotide polymorphisms in the APLNR gene and the risk of essential HT.

We conducted a search in the PubMed and Web of Science databases for eligible studies. The pooled odds ratios (ORs) with their 95% confidence intervals (CI) were calculated using random-effects models when heterogeneity was expected across the studies. Otherwise, fixed-effect models were used.

Regarding the SNP rs7119375, 5 studies were analyzed, which included a total of 3567 essential HT patients and 3256 healthy controls. Four of the 5 studies were from China and 1 was from Mexico. The meta-analysis showed the existence of a significant association between the AA genotype of rs7119375 and the risk of developing essential HT in the Chinese population, as determined using additive and recessive models (OR, 2.11; 95% CI, 1.12–3.96; I
2 = 86% for AA vs GG. OR, 1.53; 95% CI, 1.21–1.94; I
2 = 28% for AA vs AG. OR, 1.88; 95% CI, 1.13–3.12; I
2 = 79% for AA vs AG + GG).

Our study showed, for the first time, the existence of an association between rs7119375 and the risk of development of essential HT in the Chinese population, although the sample size was small and there was considerable population heterogeneity. The apelin/APLNR system could be a novel therapeutic target for the treatment of essential HT, and more studies are warranted to further investigate the association.
The general public new views on deceased organ donation in China
Authors: Li Xiaoshan , Miao Junyan , Gao Rong , Hu Di , Qian Gongtao , Wei Dong , Zhou Jianmei , Zhang Lihua , Xu Weiwei , Chen Jingyu , Hu Chunxiao
Published: December 2020

Background:

The organ donation in China has developed rapidly since fully launched donations after citizens death in 2015. This study was conducted to evaluate how the Chinese general public views changed on deceased organ donation, and to improve the donation process.

Methods:

A total of 110 eligible studies, including 103, 410 individuals, were selected to analyze through searching PubMed, CBMdisc, CQVIP, CNKI, and Wanfang Data from Jan 1, 1990 to May 31, 2019. The pooled proportions (and 95% CIs) of cognition, attitudes and willingness related to organ donation were calculated using the Freeman–Tukey double arcsine transformation.

Results:

The pooled proportions of knowing about organ donation and willing to donate increased from 84.6% (73.0–93.4) and 32.4% (23.9–41.6) before 2015, to 86.4% (74.5–95.1) and 39.9% (32.8–47.2) after 2015, respectively. The willingness to posthumous organ donation for cornea, heart, kidney, and liver had a significant improvement. Especially, the proportion of willingness to donate cornea increased to 56.0% (43.3–68.3) after 2015, from 39.2% (31.2–47.4) before 2015. However, although 69.7% (62.7–76.4) of participants approved the deceased organ donation, only 35.6% (29.7–41.8) and 43.9% (37.2–50.8) were willing to donate their own and relatives organs postmortem, respectively. The leading reasons for refraining from donating organs postmortem were distrusting the medical professionals (49.8%, 35.2–64.4) and traditional Chinese values (40.6%, 32.4–49.0). Popularizing knowledge about organ donation (61.5%, 45.7–76.1), humanitarian aid (57.1%, 48.8–65.3), and priority of using donated organs for relatives (53.1%, 30.8–74.7) were the applauded strategies to improve the willingness to posthumous organ donation.

Conclusions:

The willingness toward posthumous organ donation has a significant improvement among Chinese general public since 2015, however, several important measures still need to be taken to promote the favorable attitudes and willingness toward organ donation.
Lung ultrasound vs chest radiography in the diagnosis of children pneumonia
Authors: Yan Jun-Hong , Yu Na , Wang Yue-Heng , Gao Yan-Bing , Pan Lei
Published: December 2020

Background:

The aim of this meta-analysis was to evaluate the diagnostic value of lung ultrasound (LUS) in comparison to chest radiography (CXR) in children with pneumonia.

Methods:

Computer-based retrieval was performed on PubMed and EMBASE. Quality was evaluated according to the quality assessment of diagnostic accuracy studies-2, and Meta-Disc was adopted to perform meta-analysis. Heterogeneity was assessed using Q and I

2
statistics. The pooled sensitivity, specificity, and diagnostic odds ratio (DOR) with 95% confidence intervals (CIs) as the primary outcomes were calculated for each index test.

Results:

Twenty two studies with a total of 2470 patients met the inclusion criteria. Our results showed that the pooled sensitivity, specificity, and DOR for children with pneumonia diagnosed by LUS were 0.95 (95% CI: 0.94 to 0.96), 0.90 (95% CI: 0.87 to 0.92), and 137.49 (95% CI: 60.21 to 313.98), respectively. The pooled sensitivity, specificity, and DOR for pediatric pneumonia diagnosed by CXR was 0.91 (95% CI: 0.90 to 0.93), 1.00 (95% CI: 0.99 to 1.00), and 369.66 (95% CI: 137.14 to 996.47), respectively. Four clinical signs, including pulmonary consolidation, positive air bronchogram, abnormal pleural line, and pleural effusion were most frequently observed using LUS in the screening of children with pneumonia.

Conclusions:

The available evidence suggests that LUS is a reliable, valuable, and alternative method to CXR for the diagnosis of pediatric pneumonia.
Measuring Primary Care Exam Length Using Electronic Health Record Data
Authors: Neprash Hannah T. , Everhart Alexander , McAlpine Donna , Smith Laura Barrie , Sheridan Bethany , Cross Dori A.
Published: December 2020

Background:

Physicians’ time with patients is a critical input to care, but is typically measured retrospectively through survey instruments. Data collected through the use of electronic health records (EHRs) offer an alternative way to measure visit length.

Objective:

To measure how much time primary care physicians spend with their patients, during each visit.

Research Design:

We used a national source of EHR data for primary care practices, from a large health information technology company. We calculated exam length and schedule deviations based on timestamps recorded by the EHR, after implementing sequential data refinements to account for non–real-time EHR use and clinical multitasking. Observational analyses calculated and plotted the mean, median, and interquartile range of exam length and exam length relative to scheduled visit length.

Subjects:

A total of 21,010,780 primary care visits in 2017.

Measures:

We identified primary care visits based on physician specialty. For these visits, we extracted timestamps for EHR activity during the exam. We also extracted scheduled visit length from the EHR’s practice management functionality.

Results:

After data refinements, the average primary care exam was 18.0 minutes long (SD=13.5 min). On average, exams ran later than their scheduled duration by 1.2 minutes (SD=13.5 min). Visits scheduled for 10 or 15 minutes were more likely to exceed their allotted time than visits scheduled for 20 or 30 minutes.

Conclusions:

Time-stamped EHR data offer researchers and health systems an opportunity to measure exam length and other objects of interest related to time.
Impact of an Emergency Department-to-Home Transitional Care Intervention on Health Service Use in Medicare Beneficiaries
Authors: Schumacher Jessica R. , Lutz Barbara J. , Hall Allyson G. , Harman Jeffrey S. , Turner Kristen , Brumback Babette A. , Hendry Phyllis , Carden Donna L.
Published: December 2020

Background:

Hospital-based acute care [emergency department (ED) visits and hospitalizations] that is preventable with high-quality outpatient care contributes to health care system waste and patient harm.

Objective:

To test the hypothesis that an ED-to-home transitional care intervention reduces hospital-based acute care in chronically ill, older ED visitors.

Research Design:

Convergent, parallel, mixed-methods design including a randomized controlled trial.

Setting:

Two diverse Florida EDs.

Subjects:

Medicare fee-for-service beneficiaries with chronic illness presenting to the ED.

Intervention:

The Coleman Care Transition Intervention adapted for ED visitors.

Measures:

The main outcome was hospital-based acute care within 60 days of index ED visit. We also assessed office-based outpatient visits during the same period.

Results:

The Intervention did not significantly reduce return ED visits or hospitalizations or increase outpatient visits. In those with return ED visits, the Intervention Group was less likely to be hospitalized than the Usual Care Group. Interview themes describe a cycle of hospital-based acute care largely outside patients’ control that may be difficult to interrupt with a coaching intervention.

Conclusions and Relevance:

Structural features of the health care system, including lack of access to timely outpatient care, funnel patients into the ED and hospital admission. Reducing hospital-based acute care requires increased focus on the health care system rather than patients’ care-seeking decisions.
Digital versus analog PET/CT in patients with known or suspected liver metastases
Authors: Fuentes-Ocampo Francisco , López-Mora Diego Alfonso , Flotats Albert , Camacho Valle , Sizova Marina , Abouzian Safae , Duch Joan , Fernández Alejando , Estorch Montserrat , Carrió Ignasi
Published: December 2020

Aim

To assess if digital PET/CT improves liver lesion detectability compared to analog PET/CT in patients with known or suspected liver metastases.

Materials and methods

We prospectively included 83 cancer patients, with one or more of these conditions: history of liver metastases, clinical risk of having liver metastases or presence of suspected liver metastases on the first of the two PET/CTs. All patients were consecutively scanned on each PET/CT on the same day after a single [18F]fluorodeoxyglucose dose injection. The order of acquisition was randomly assigned. Three nuclear medicine physicians assessed both PET/CTs by counting the foci of high uptake suspicious of liver metastases. Findings were correlated with appropriate reference standards; 19 patients were excluded from the analysis due to insufficient lesion nature confirmation. The final sample consisted of 64 patients (34 women, mean age 68 ± 12 years).

Results

As per-patient analysis, the mean number of liver lesions detected by the digital PET/CT (3.84 ± 4.25) was significantly higher than that detected by the analog PET/CT (2.91 ± 3.31); P < 0.001. Fifty-five patients had a positive PET/CT study for liver lesions. In 26/55 patients (47%), the digital PET/CT detected more lesions; 7/26 patients (27%) had detectable lesions only by the digital system and had <10 mm of diameter. Twenty-nine patients had the same number of liver lesions detected by both systems. In nine patients both PET/CT systems were negative for liver lesions.

Conclusion

Digital PET/CT offers improved detectability of liver lesions over the analog PET/CT in patients with known or suspected liver metastases.
Robotic-assisted locomotor treadmill therapy does not change gait pattern in children with cerebral palsy
Authors: Petrarca Maurizio , Frascarelli Flaminia , Carniel Sacha , Colazza Alessandra , Minosse Silvia , Tavernese Emanuela , Castelli Enrico
Published: December 2020

Although robotic-assisted locomotor treadmill therapy is utilized on children with cerebral palsy (CP), its impact on the gait pattern in childhood is not fully described. We investigated the outcome of robotized gait training focusing on the gait pattern modifications and mobility in individuals with CP. An additional intention is to compare our results with the previous literature advancing future solutions. Twenty-four children with diplegic CP (average age 6.4 years old with Gross Motor Functional Classification System range I–IV) received robotized gait training five times per week for 4 weeks. Gait analysis and Gross Motor Function Measurement (GMFM) assessments were performed before and at the end of the treatment. Gait analysis showed inconsistent modifications of the gait pattern. GMFM showed a mild improvement of the dimension D in all subjects, while dimension E changed only in the younger and more severely affected patients. In this study, a detailed investigation comprehensive of electromyography patterns, where previous literature reported only sparse data without giving information on the whole gait pattern, were conducted. We carried on the analysis considering the age of the participants and the severity of the gait function. The findings differentiate the concept of specific pattern recovery (no gait pattern changes) from the concept of physical training (mild GMFM changes).
TED Talk
Authors: Stillwell Susan B.
Published: December 2020

Background

Evidence-based practice (EBP) is key to improve outcomes and requires health care professionals to appraise research findings. Interpreting statistical findings can be daunting for nursing students.

Purpose

The purpose of this study was to evaluate student perception and satisfaction with a TED Talk assignment as an approach to understand concepts used to appraise evidence.

Methods

A descriptive design was used to survey students about their experience creating and delivering a TED Talk to their peers in an EBP course.

Results

The assignment helped students engage in learning research/EBP concepts, and they rated the assignment moderately helpful to understand components to appraise evidence. The majority of students were neutral toward or disagreed the TED Talk assignment was a satisfactory experience. Almost 60% of the students recommended the assignment be retained in the course.

Conclusions

The TED Talk assignment was not a universally satisfactory experience. Differences in faculty approach in the course sections may have influenced the findings.
Induced brain magnetic activities related to salient birdsong under noisy conditions
Authors: Yano Hajime , Soeta Yoshiharu
Published: December 2020

Objective

Birdsong sounds are often used to inform visually-challenged people about the presence of basic infrastructures, and therefore need to be salient in noisy urban environments. How salient sounds are processed in the brain could inform us about the optimal birdsong in such environments. However, brain activity related to birdsong salience is not yet known.

Methods

Oscillatory magnetoencephalographic (MEG) activities and subjective salience induced by six birdsongs under three background noise conditions were measured. Thirteen participants completed the MEG measurements and 11 participants took part in the paired-comparison tests. We estimated the power of induced oscillatory activities, and explored the relationship between subjective salience of birdsongs and the power of induced activities using sparse regression analysis.

Results

According to sparse regression analysis, the subjective salience was explained by the power of induced alpha (8–13 Hz) in the frontal region, induced beta (13–30 Hz) in the occipital region, and induced gamma (30–50 Hz) in the parietal region. The power of the frontal alpha and parietal gamma activities significantly varied across both birds and noise conditions.

Conclusion

These results indicate that frontal alpha activity is related to the salience of birdsong and that parietal gamma activity is related to differences in salience across noisy environments. These results suggest that salient birdsong under a noisy environment activates the bottom-up attention network.
Epigenetics in bipolar disorder: a critical review of the literature
Authors: Legrand Adrien , Iftimovici Anton , Khayachi Anouar , Chaumette Boris
Published: December 2020

Introduction

Bipolar disorder (BD) is a chronic, disabling disease characterised by alternate mood episodes, switching through depressive and manic/hypomanic phases. Mood stabilizers, in particular lithium salts, constitute the cornerstone of the treatment in the acute phase as well as for the prevention of recurrences. The pathophysiology of BD and the mechanisms of action of mood stabilizers remain largely unknown but several pieces of evidence point to gene x environment interactions. Epigenetics, defined as the regulation of gene expression without genetic changes, could be the molecular substrate of these interactions. In this literature review, we summarize the main epigenetic findings associated with BD and response to mood stabilizers.

Methods

We searched PubMed, and Embase databases and classified the articles depending on the epigenetic mechanisms (DNA methylation, histone modifications and non-coding RNAs).

Results

We present the different epigenetic modifications associated with BD or with mood-stabilizers. The major reported mechanisms were DNA methylation, histone methylation and acetylation, and non-coding RNAs. Overall, the assessments are poorly harmonized and the results are more limited than in other psychiatric disorders (e.g. schizophrenia). However, the nature of BD and its treatment offer excellent opportunities for epigenetic research: clear impact of environmental factors, clinical variation between manic or depressive episodes resulting in possible identification of state and traits biomarkers, documented impact of mood-stabilizers on the epigenome.

Conclusion

Epigenetic is a growing and promising field in BD that may shed light on its pathophysiology or be useful as biomarkers of response to mood-stabilizer.
Tessaracoccus coleopterorum sp. nov., isolated from the intestine of the dark diving beetle, Hydrophilus acuminatus
Authors: Hyun Dong-Wook , Sung Hojun , Kim Pil Soo , Lee Jae-Yun , Jeong Yun-Seok , Yun Ji-Hyun , Choi Jee-Won , Han Jeong Eun , Lee So-Yeon , Tak Euon Jung , Lee June-Young , Kim Hyun Sik , Bae Jin-Woo
Published: December 2020

A polyphasic taxonomic approach was used to characterize a novel bacterium, designated as strain HDW20T, isolated from the intestine of the dark diving beetle Hydrophilus acuminatus. The isolate was Gram-stain-positive, facultatively anaerobic, non-motile, coccus-shaped, and formed pale orange colonies. Phylogenetic analysis based on 16S rRNA gene sequences and genome sequences showed that the isolate belonged to the genus

Tessaracoccus

in the phylum

Actinobacteria

and was closely related to

T. flavescens

SST-39T,

T. defluvii

JCM 17540T, and

T. aquimaris

NSG39T, with the highest 16S rRNA gene sequence similarity of 98.5 % and a highest average nucleotide identity (ANI) value of 80.6 %. The major cellular fatty acids were C18 : 1
 ω9c and anteiso-C15 : 0. The main respiratory quinone was MK-9 (H4). The major polar lipid components were phosphatidylglycerol and diphosphatidylglycerol. The genomic DNA G+C content was 69.0 %. The isolate contains ʟʟ-diaminopimelic acid, ʟ-alanine, and ʟ-lysine as amino acid components, and ribose, glucose, and galactose as sugar components of the cell wall peptidoglycan. The results of phylogenetic, phenotypic, chemotaxonomic, and genotypic analyses suggested that strain HDW20T represents a novel species within the genus

Tessaracoccus

. We propose the name Tessaracoccus coleopterorum sp. nov. The type strain is HDW20T (=KACC 21348T=KCTC 49324T=JCM 33674T).
Anomalous epithelial variations and ectopic inflammatory response in chronic obstructive pulmonary disease
Authors: Watanabe Naoaki , Nakayama Jun , Fujita Yu , Mori Yutaro , Kadota Tsukasa , Shimomura Iwao , Ohtsuka Takashi , Okamoto Koji , Araya Jun , Kuwano Kazuyoshi , Yamamoto Yusuke
Published: December 2020

Phenotypic alterations in the lung epithelium have been widely implicated in Chronic obstructive pulmonary disease (COPD) pathogenesis, but the precise mechanisms orchestrating this persistent inflammatory process remain unknown due to the complexity of lung parenchymal and mesenchymal architecture. To identify cell type-specific mechanisms and cell-cell interactions among the multiple lung resident cell types and inflammatory cells that contribute to COPD progression, we profiled 52,764 cells from lungs of COPD patients, non-COPD smokers, and never smokers using single-cell RNA sequencing technology. We predicted pseudotime of cell differentiation and cell-to-cell interaction networks in COPD. While epithelial components in never-smokers were relatively uniform, smoker groups represent extensive heterogeneity in epithelial cells, particularly in alveolar type 2 (AT2) clusters. Among AT2 cells, which are generally regarded as alveolar progenitors, we identified a unique subset that significantly increased in COPD patients, and specifically expressed a series of chemokines and PD-L1. A trajectory analysis revealed that the inflammatory AT2 cell subpopulation followed a unique differentiation path, and a prediction model of cell-to-cell interactions inferred significantly increased intercellular networks of inflammatory AT2 cells. Our results identify previously unidentified cell subsets and provide an insight into the biological and clinical characteristics of COPD pathogenesis.
A two-pronged approach for rapid and high-throughput SARS-CoV-2 nucleic acid testing
Authors: Gandotra Neeru , Tikhonova Irina , Cheemarla Nagarjuna R. , Knight James , Foxman Ellen , Giraldez Antonio , Shen Peidong , Bilguvar Kaya , Scharfe Curt
Published: December 2020

Improved molecular screening and diagnostic tools are needed to substantially increase SARS-CoV-2 testing capacity and throughput while reducing the time to receive test results. Here we developed multiplex reverse transcriptase polymerase chain reaction (m-RT-PCR) for detection of SARS-CoV-2 using rapid DNA electrophoresis and alternatively using multiplex viral sequencing (mVseq). For RNA specimens extracted from nasopharyngeal (NP) swabs in viral transport media (VTM), our assays achieved a sensitivity for SARS-CoV-2 detection corresponding to cycle threshold (Ct) of 37.2 based on testing of these specimens using quantitative reverse transcription PCR (RT-qPCR). For NP swab-VTM specimens without prior RNA extraction, sensitivity was reduced to Ct of 31.6, which was due to lower concentration of SARS-CoV-2 genome copies in VTM compared to RNA-extracted samples. Assay turnaround time was 60 minutes using rapid gel electrophoresis, 90 minutes using Agilent Bioanalyzer, and 24-48 hours using Illumina sequencing, the latter of which required a second PCR to produce a sequence-ready library using m-RT-PCR products as the template. Our assays can be employed for high-throughput sequencing-based detection of SARS-CoV-2 directly from a clinical specimen without RNA isolation, while ease-of-use and low cost of the electrophoresis-based readout enables screening, particularly in resource-constrained settings.
Impact of intra-partum Azithromycin on carriage of group A streptococcus in The Gambia: a posthoc analysis of a double-blind randomized placebo-controlled trial
Authors: Jagne Isatou , Keeley Alexander J. , Bojang Abdoulie , Camara Bully , Jallow Edrissa , Senghore Elina , Oluwalana Claire , Bah Saikou Y. , Turner Claire E. , Sesay Abdul Karim , D’Alessandro Umberto , Bottomley Christian , de Silva Thushan I. , Roca Anna
Published: December 2020

Background

Group A Streptococcus (GAS) is a major human pathogen and an important cause of maternal and neonatal sepsis.

Methods

We performed a posthoc analysis of a double-blind, placebo-controlled randomized-trial (ratio 1:1) carried out in The Gambia to determine the impact of one oral dose (2g) of intra-partum azithromycin on maternal and neonatal GAS carriage. Breast milk, nasopharyngeal and vaginal swabs were collected at different time points during 4 weeks post-treatment. All samples were processed using conventional microbiology techniques. Whole genome sequencing (WGS) of GAS isolates was performed by Illumina MiSeq platform.

Results

We randomized 829 mothers who delivered 843 babies. GAS carriage in mothers in the azithromycin arm was lower in breast milk (0.28% vs 2.48%, Prevalence Ratio (PR)=0.11, 95% CI 0.01-0.90) and the nasopharynx (0.28% vs 1.93%, PR=0.15, 95% CI 0.02-1.19), but not in the vaginal tract (1.99% vs 1.93%, PR=1.03, 95% CI 0.37-2.91). Among neonates, GAS carriage in the nasopharynx was slightly lower in the azithromycin arm (0.57% vs 1.91%, PR=0.30, 95% CI 0.06-1.42). Prevalence of azithromycin-resistant GAS was similar in both arms, except for a higher prevalence in the vaginal tract among women in the azithromycin arm (1.99% vs 0.28%, PR=7.24, 95% CI 0.87-56.92). WGS revealed ten of the 45 GAS isolates (22.2%) were Streptococcus dysgalactiae subspecies equisimilis expressing Lancefield group A carbohydrate (SDSE(A)). All SDSE(A) isolates were azithromycin-resistant, harbouring macrolide resistant genes msrD and mefA.

Conclusions

Oral intra-partum azithromycin reduced prevalence of GAS carriage among mothers and neonates. Azithromycin-resistant SDSE(A) carriage was observed among participants treated with azithromycin.

Short Summary

Group A streptococcus (GAS) is an important cause of sepsis. One oral dose (2g) of intra-partum azithromycin reduced maternal and neonatal GAS carriage. However, azithromycin-resistant Streptococcus dysgalactiae subspecies equisimilis expressing Lancefield group A carbohydrate was detected in women receiving azithromycin.
Lipid storm within the lungs of severe COVID-19 patients: Extensive levels of cyclooxygenase and lipoxygenase-derived inflammatory metabolites
Authors: Archambault Anne-Sophie , Zaid Younes , Rakotoarivelo Volatiana , Doré Étienne , Dubuc Isabelle , Martin Cyril , Amar Youssef , Cheikh Amine , Fares Hakima , El Hassani Amine , Tijani Youssef , Laviolette Michel , Boilard Éric , Flamand Louis , Flamand Nicolas
Published: December 2020

BACKGROUND

Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2) is the infectious agent responsible for Coronavirus disease 2019 (COVID-19). While SARS-CoV-2 infections are often benign, there are also severe COVID-19 cases, characterized by severe bilobar pneumonia that can decompensate to an acute respiratory distress syndrome, notably characterized by increased inflammation and a cytokine storm. While there is no cure against severe COVID-19 cases, some treatments significantly decrease the severity of the disease, notably aspirin and dexamethasone, which both directly or indirectly target the biosynthesis (and effects) of numerous bioactive lipids.

OBJECTIVE

Our working hypothesis was that severe COVID-19 cases necessitating mechanical ventilation were characterized by increased bioactive lipid levels modulating lung inflammation. We thus quantitated several lung bioactive lipids using liquid chromatography combined to tandem mass spectrometry.

RESULTS

We performed an exhaustive assessment of the lipid content of bronchoalveolar lavages from 25 healthy controls and 33 COVID-19 patients necessitating mechanical ventilation. Severe COVID-19 patients were characterized by increased fatty acid levels as well as an accompanying inflammatory lipid storm. As such, most quantified bioactive lipids were heavily increased. There was a predominance of cyclooxygenase metabolites, notably TXB2>> PGE2∼ 12-HHTrE > PGD2. Leukotrienes were also increased, notably LTB4, 20-COOH-LTB4, LTE4, and eoxin E4. 15-lipoxygenase metabolites derived from linoleic, arachidonic, eicosapentaenoic and docosahexaenoic acids were also increased. Finally, yet importantly, specialized pro-resolving mediators, notably lipoxin A4and the D-series resolvins, were also found at important levels, underscoring that the lipid storm occurring in severe SARS-CoV-2 infections involves pro- and anti-inflammatory lipids.

CONCLUSIONS

Our data unmask the important lipid storm occurring in the lungs of patients afflicted with severe COVID-19. We discuss which clinically available drugs could be helpful at modulating the lipidome we observed in the hope of minimizing the deleterious effects of pro-inflammatory lipids and enhancing the effects of anti-inflammatory and/or pro-resolving lipids.
Evidence forGRNas part of a neuroinflammatory mechanism connecting common neurodegenerative diseases
Authors: Nalls Mike A. , Blauwendraat Cornelis , Sargent Lana , Vitale Dan , Leonard Hampton , Iwaki Hirotaka , Song Yeajin , Bandres-Ciga Sara , Menden Kevin , Faghri Faraz , Heutink Peter , Cookson Mark R. , Singleton Andrew B.
Published: December 2020

Background

Previous research using genome wide association studies (GWAS) has identified variants that may contribute to lifetime risk of multiple neurodegenerative diseases. However, whether there are common mechanisms that link neurodegenerative diseases is uncertain. Here, we focus on one gene,GRN, encoding progranulin, and the potential mechanistic interplay between genetic risk, gene expression in the brain and inflammation across multiple common neurodegenerative diseases.

Methods

We utilized GWAS, expression quantitative trait locus (eQTL) mapping and Bayesian colocalization analyses to evaluate potential causal and mechanistic inferences. We integrate various molecular data types from public resources to infer disease connectivity and shared mechanisms using a data driven process.

Findings

eQTL analyses combined with GWAS identified significant functional associations between increasing genetic risk in theGRNregion and decreased expression of the gene in Parkinson’s, Alzheimer’s and amyotrophic lateral sclerosis. Additionally, colocalization analyses show a connection between blood based inflammatory biomarkers relating to platelets andGRNexpression in the frontal cortex.

Interpretation

GRNexpression mediates neuroinflammation function related to general neurodegeneration. This analysis suggests shared mechanisms for Parkinson’s, Alzheimer’s and amyotrophic lateral sclerosis.

Funding

National Institute on Aging, National Institute of Neurological Disorders and Stroke, and the Michael J. Fox Foundation.
Diet, physical activity and behavioural disinhibition in middle-aged and older adults: a UK Biobank study
Authors: Schweren Lizanne JS , van Rooij Daan , Shi Huiqing , Arias-Vasquez Alejandro , Li Lin , Larsson Henrik , Kvalvik Liv Grimstvedt , Haavik Jan , Buitelaar Jan , Hartman Catharina A
Published: December 2020

Background and aims

Behavioural disinhibition is a prominent feature of multiple psychiatric disorders, and has been associated with poor long-term somatic health outcomes. Modifiable lifestyle factors including diet and moderate-to-vigorous physical activity (MVPA) may be associated with behavioural disinhibition, but their shared and unique contributions have not previously been quantified.

Methods

N=157,354 UK Biobank participants who completed the online mental health assessment were included (age 40-69, 2006-2010). Using principal component analyses, we extracted a single disinhibition score and four dietary component scores (prudent diet, elimination of wheat/dairy/eggs, meat consumption, full-cream dairy consumption). In addition, latent profile analysis assigned participants to one of five empirical dietary groups: moderate-healthy, unhealthy, restricted, meat-avoiding, low-fat dairy. Participants self-reported MVPA in minutes/week. Disinhibition was regressed on the four dietary components, the dietary grouping variable and MVPA.

Results

in men and women, behavioural disinhibition was negatively associated with prudent diet scores, and positively associated with wheat/dairy/eggs elimination. In men only, disinhibition was associated with consumption of meat and full-cream dairy products. Comparing groups, disinhibition was lower in the moderate-and-prudent diet (reference) group compared to all other groups. Absolute βs ranged from 0.02-0.13 indicating very weak effects. Disinhibition was not associated with MVPA.

Conclusions

Among middle-aged and older adults, behavioural disinhibition is associated with multiple features of diet. While the observational nature of UK Biobank does not allow causal inference, our findings foster specific hypotheses (e.g. early malnutrition, elevated immune-response, dietary restraint) to be tested in alternative study designs.
How to predict relapse in leukemia using time series data: A comparative in silico study
Authors: Hoffmann Helene , Baldow Christoph , Zerjatke Thomas , Gottschalk Andrea , Wagner Sebastian , Karg Elena , Niehaus Sebastian , Roeder Ingo , Glauche Ingmar , Scherf Nico
Published: December 2020

Risk stratification and treatment decisions for leukemia patients are regularly based on clinical markers determined at diagnosis, while measurements on system dynamics are often neglected. However, there is increasing evidence that linking quantitative time-course information to disease outcomes can improve the predictions for patient-specific treatment responses.

We designed a synthetic experiment to compare different computational methods with respect to their ability to accurately predict relapse for chronic and acute myeloid leukemia treatment. Technically, we used clinical reference data to first fit a model and then generate de novo model simulations of individual patients’ time courses for which we can systematically tune data quality (i.e. measurement error) and quantity (i.e. number of measurements). Based hereon, we compared the prediction accuracy of three different computational methods, namely mechanistic models, generalized linear models, and deep neural networks that have been fitted to the reference data.

Our results show that data quality has a higher impact on prediction accuracy than the specific choice of the particular method. We further show that adapted treatment and measurement schemes can considerably improve the prediction accuracy.

Our proof-of-principle study highlights how computational methods and optimized data acquisition strategies can improve risk assessment and treatment of leukemia patients.
Use of Public Data to Describe COVID-19 Contact Tracing in China during January 20–February 29, 2020
Authors: Dirlikov Emilio , Zhou Suizan , Han Lifeng , Li Zhijun , Hao Ling , Millman Alexander J. , Marston Barbara
Published: December 2020

Objective

Although contact tracing is generally not used to control influenza pandemics, China and several countries in the Western Pacific Region employed contact tracing as part of COVID-19 response activities. To improve understanding on the use of contact tracing for COVID-19 emergency public health response activities, we describe reported COVID-19 contacts traced and quarantined in China and a proxy for number of reported contacts traced per reported case.

Methods

We abstracted publicly available online aggregate data reported from China’s National Health Commission and provincial health commissions’ COVID-19 daily situational reports for January 20–February 29, 2020. The number of new contacts traced by report date was computed as the difference between total contacts traced on consecutive reports. A proxy for the number of contacts traced per case was computed as the number of new contacts traced divided by the number of new cases.

Results

During January 20–February 29, 2020, China reported 80,968 new COVID-19 cases (Hubei Province = 67,608 [83%]), and 659,899 contacts traced (Hubei Province = 265,617 [40%]). Non-Hubei provinces reported more contacts traced per case than Hubei Province; this difference increased over time.

Discussion

Along with other NPI used in China, contact tracing likely contributed to reducing SARS-CoV-2 transmission by quarantining a large number of potentially infected contacts. Despite reporting only 15% of total cases, non-Hubei provinces had 1.5 times more reported contacts traced compared to Hubei Province. Contract tracing may have been more complete in areas and periods with lower case counts.