bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparative Toxicogenomics Database (CTD): update 2021
Authors: Davis Allan Peter , Grondin Cynthia J , Johnson Robin J , Sciaky Daniela , Wiegers Jolene , Wiegers Thomas C , Mattingly Carolyn J
Published: October 2020

The public Comparative Toxicogenomics Database (CTD; http://ctdbase.org/) is an innovative digital ecosystem that relates toxicological information for chemicals, genes, phenotypes, diseases, and exposures to advance understanding about human health. Literature-based, manually curated interactions are integrated to create a knowledgebase that harmonizes cross-species heterogeneous data for chemical exposures and their biological repercussions. In this biennial update, we report a 20% increase in CTD curated content and now provide 45 million toxicogenomic relationships for over 16 300 chemicals, 51 300 genes, 5500 phenotypes, 7200 diseases and 163 000 exposure events, from 600 comparative species. Furthermore, we increase the functionality of chemical–phenotype content with new data-tabs on CTD Disease pages (to help fill in knowledge gaps for environmental health) and new phenotype search parameters (for Batch Query and Venn analysis tools). As well, we introduce new CTD Anatomy pages that allow users to uniquely explore and analyze chemical–phenotype interactions from an anatomical perspective. Finally, we have enhanced CTD Chemical pages with new literature-based chemical synonyms (to improve querying) and added 1600 amino acid-based compounds (to increase chemical landscape). Together, these updates continue to augment CTD as a powerful resource for generating testable hypotheses about the etiologies and molecular mechanisms underlying environmentally influenced diseases.
BastionHub: a universal platform for integrating and analyzing substrates secreted by Gram-negative bacteria
Authors: Wang Jiawei , Li Jiahui , Hou Yi , Dai Wei , Xie Ruopeng , Marquez-Lago Tatiana T , Leier André , Zhou Tieli , Torres Von , Hay Iain , Stubenrauch Christopher , Zhang Yanju , Song Jiangning , Lithgow Trevor
Published: October 2020

Gram-negative bacteria utilize secretion systems to export substrates into their surrounding environment or directly into neighboring cells. These substrates are proteins that function to promote bacterial survival: by facilitating nutrient collection, disabling competitor species or, for pathogens, to disable host defenses. Following a rapid development of computational techniques, a growing number of substrates have been discovered and subsequently validated by wet lab experiments. To date, several online databases have been developed to catalogue these substrates but they have limited user options for in-depth analysis, and typically focus on a single type of secreted substrate. We therefore developed a universal platform, BastionHub, that incorporates extensive functional modules to facilitate substrate analysis and integrates the five major Gram-negative secreted substrate types (i.e. from types I–IV and VI secretion systems). To our knowledge, BastionHub is not only the most comprehensive online database available, it is also the first to incorporate substrates secreted by type I or type II secretion systems. By providing the most up-to-date details of secreted substrates and state-of-the-art prediction and visualized relationship analysis tools, BastionHub will be an important platform that can assist biologists in uncovering novel substrates and formulating new hypotheses. BastionHub is freely available at http://bastionhub.erc.monash.edu/.
Cross-Sectional Association Between Lifetime Use of Electronic Cigarettes With or Without Marijuana and Self-Reported Past 12-Month Respiratory Symptoms as well as Lifetime Respiratory Diseases in U.S. Adults
Authors: Xie Zidian , Li Dongmei
Published: October 2020

Introduction

The use of electronic cigarettes (vaping), especially with marijuana, has become increasingly popular among adults.

Aims and Methods

The Population Assessment of Tobacco and Health study Wave 4 data on 33 606 adult participants who indicated ever using electronic cigarettes were included in the study. By controlling for confounding variables (such as age and smoking history), multivariable weighted logistic regression models were used to examine the cross-sectional association between lifetime e-cigarette use with or without marijuana and self-reported past 12-month respiratory symptoms as well as lifetime respiratory diseases.

Results

Compared to adults who never vaped, adults who had ever vaped with marijuana had a significantly higher association with self-reported past 12-month respiratory symptoms but not lifetime respiratory diseases. Compared to adults who had ever vaped without marijuana, adults who had ever vaped at least sometimes with marijuana had a significantly greater risk of having wheezing/whistling in the chest (adjusted odds ratio [aOR] = 1.21, 95% confidence interval [CI]: 1.01, 1.44), chest sounded wheezy during or after exercise (aOR = 1.59, 95% CI: 1.31, 1.93), and had a dry cough at night (aOR = 1.35, 95% CI: 1.16, 1.57), while adults who had ever vaped rarely with marijuana had a significantly greater risk of having wheezing/whistling in the chest (aOR = 1.31, 95% CI: 1.06, 1.61), chest sounded wheezy during or after exercise (aOR = 1.24, 95% CI: 1.01, 1.52), and had a dry cough at night (aOR = 1.24, 95% CI: 1.04, 1.47).

Conclusions

Lifetime e-cigarette use with marijuana is associated with self-reported past 12-month respiratory symptoms in adults.

Implications

The use of e-cigarettes with marijuana has become prevalent in recent years. Our cross-sectional study suggests that there may be respiratory health symptoms associated with ever vaping with marijuana that is independent of nicotine vaping, which should raise public awareness of potential health risks associated with the use of e-cigarettes with marijuana. Further longitudinal studies on the respiratory health effects of e-cigarette use with marijuana are warranted.
Tofacitinib counteracts IL-6 overexpression induced by deficient autophagy: implications in Sjögren’s syndrome
Authors: Barrera María-José , Aguilera Sergio , Castro Isabel , Matus Soledad , Carvajal Patricia , Molina Claudio , González Sergio , Jara Daniela , Hermoso Marcela , González María-Julieta
Published: October 2020

Objective

Altered homeostasis of salivary gland (SG) epithelial cells in Sjögren’s syndrome (SS) could be the initiating factor that leads to inflammation, secretory dysfunction and autoimmunity. Autophagy is an important homeostatic mechanism, whose deficiency is associated with inflammation and accumulation of Janus kinase (JAK)–signal transducer and activator of transcription (STAT) components. We aimed to evaluate whether autophagy is altered in labial SG (LSG) epithelial cells from primary SS (pSS) patients and whether this contributes to inflammation through the JAK–STAT pathway. Furthermore, we investigated the anti-inflammatory effect of the JAK inhibitor tofacitinib in autophagy-deficient (ATG5 knockdown) three-dimensional (3D)-acini.

Methods

We analysed LSG biopsies from 12 pSS patients with low focus score and 10 controls. ATG5-deficient 3D-acini were generated and incubated with IL-6 in the presence or absence of tofacitinib. Autophagy markers, pro-inflammatory cytokine expression, and JAK–STAT pathway activation were evaluated by PCR or western blot, along with correlation analyses between the evaluated markers and clinical parameters.

Results

LSG from pSS patients showed increased p62 and decreased ATG5 expression, correlating negatively with increased activation of JAK–STAT pathway components (pSTAT1 and pSTAT3). Increased expression of STAT1 and IL-6 correlated with EULAR Sjögren's syndrome disease activity index and the presence of anti-Ro antibodies. ATG5-deficient 3D-acini reproduced the findings observed in LSG from pSS patients, showing increased expression of pro-inflammatory markers such as IL-6, which was reversed by tofacitinib.

Conclusion

Decreased expression of ATG5 in LSG epithelial cells from pSS patients possibly contributes to increased inflammation associated with JAK–STAT pathway activation, as evidenced in ATG5-deficient 3D-acini. Interestingly, these results suggest that tofacitinib could be used as an anti-inflammatory agent in pSS patients.
Mid-term Surgical Outcome of Posterior Decompression With Instrumented Fusion in Patients With K-line (−) Type Cervical Ossification of the Posterior Longitudinal Ligament With a 5-Year Minimum Follow-up
Authors: Furuya Takeo , Maki Satoshi , Miyamoto Takuya , Okimatsu Sho , Shiga Yasuhiro , Inage Kazuhide , Orita Sumihisa , Eguchi Yawara , Koda Masao , Yamazaki Masashi , Ohtori Seiji
Published: October 2020

Study Design:

A retrospective case-control study.

Objective:

The objective of this study was to assess mid-term surgical outcomes after posterior decompression with instrumented fusion (PDF) in patients with K-line (−) type cervical ossification of the posterior longitudinal ligament (OPLL).

Summary of Background Data:

The poor surgical outcome for K-line (−) type cervical OPLL can result from posterior decompression alone.

Materials and Methods:

We reviewed cases of K-line (−) type cervical OPLL in 24 patients who underwent PDF in our institute from 2002 to 2014. As a control, we used K-line (−) type cervical OPLL in 9 patients who underwent laminoplasty before 2002 (LMP group). The neurological status and radiographic findings were evaluated retrospectively.

Results:

The preoperative Japanese Orthopedic Association score was 7.9±2.4 points in the PDF group and 7.4±2.3 points in the LMP group (P=0.584). The postoperative Japanese Orthopedic Association score was 11.7±2.6 points in the PDF group and 9.2±2.0 points in the LMP group at a 5-year follow-up (P=0.008). The recovery rate on average was 39.0% in the PDF group and 14.9% in the LMP group at a 5-year follow-up (P=0.037). The range of motion postoperatively at the maximal spinal cord compression level decreased significantly in the PDF group. The C2–C7 angle was 2.7 degrees of kyphosis in the PDF group, whereas 5.5 degrees of kyphosis was found in the LMP group at a 5-year follow-up (P=0.303). The center of gravity of the head-C7 sagittal vertical axis was 40 mm in the PDF group and 43 mm in the LMP group (P=0.936).

Conclusions:

The relatively good surgical outcome could be obtained by PDF for patients with K-line (−)-type cervical OPLL. The addition of posterior instrumented fusion eliminated the dynamic factor at the level of maximal spinal cord compression.

Level of Evidence:

Level IV.
Guidelines on How to Perform a Systematic Review in Spine Surgery
Authors: Koslosky Ezekial , Gendelberg David , Zhu Jimmy
Published: October 2020

Primary literature can be contradictory due to a multitude of factors, including poorly designed studies, error types, and confounding factors, and thus literature reviews can be difficult and time-consuming. Systematic reviews are designed to provide unbiased and comprehensive comparisons of relevant primary studies. This method is considered superior to traditional literature reviews due to the unbiased consideration of a broad number of sources rather than a limited literature review. This article will provide guidance for performing a systematic review, including framing a question, selecting studies with inclusion and exclusion criteria, evaluating primary literature, and explaining analysis types.
Noninvasive Radioablation of Ventricular Tachycardia
Authors: Athar Ammar M. , Nabors Christopher C. , Dhaduk Kartik , Yandrapalli Srikanth , Jain Anant , Moorthy Chitti R. , Halperin Edward C. , Iwai Sei , Frishman William H. , Jacobson Jason
Published: October 2020

Ventricular tachycardia (VT) occurs most commonly in the presence of structural heart disease or myocardial scarring from prior infarction. It is associated with increased mortality, especially when it results in cardiac arrest outside of a hospital. When not due to reversible causes (such as acute ischemia/infarction), placement of an implantable cardioverter-defibrillator for prevention of future sudden death is indicated. The current standard of care for recurrent VT is medical management with antiarrhythmic agents followed by invasive catheter ablation for VT that persists despite appropriate medical therapy. Stereotactic arrhythmia radioablation (STAR) is a novel, noninvasive method of treating VT that has been shown to reduce VT burden for patients who are refractory to medical therapy and/or catheter ablation, or who are unable to tolerate catheter ablation. STAR is the term applied to the use of stereotactic body radiation therapy for the treatment of arrhythmogenic cardiac tissue and requires collaboration between an electrophysiologist and a radiation oncologist. The process involves identification of VT substrate through a combination of electroanatomic mapping and diagnostic imaging (computed tomography, magnetic resonance imaging, positron emission tomography) followed by carefully guided radiation therapy. In this article, we review currently available literature describing the utilization, efficacy, safety profile, and potential future applications of STAR for the management of VT.
Building capacity for air pollution epidemiology in India
Authors: Prabhakaran Poornima , Jaganathan Suganthi , Walia Gagandeep K. , Wellenius Gregory A. , Mandal Siddhartha , Kumar Kishore , Kloog Itai , Lane Kevin , Nori-Sarma Amruta , Rosenqvist Marten , Dahlquist Marcus , Reddy K. Srinath , Schwartz Joel , Prabhakaran Dorairaj , Ljungman Petter L. S.
Published: October 2020

Air pollution represents a major public health threat in India affecting 19% of the world’s population at extreme levels. Despite this, research in India lags behind in large part due to a lack of comprehensive air pollution exposure assessment that can be used in conjunction with health data to investigate health effects. Our vision is to provide a consortium to rapidly expand the evidence base of the multiple effects of ambient air pollution. We intend to leapfrog current limitations of exposure assessment by developing a machine-learned satellite-informed spatiotemporal model to estimate daily levels of ambient fine particulate matter measuring less than 2.5 µm (PM2.5) at a fine spatial scale across all of India. To catalyze health effects research on an unprecedented scale, we will make the output from this model publicly available. In addition, we will also apply these PM2.5 estimates to study the health outcomes of greatest public health importance in India, including cardiovascular diseases, chronic obstructive pulmonary disease, pregnancy (and birth) outcomes, and cognitive development and/or decline. Thus, our efforts will directly generate actionable new evidence on the myriad effects of air pollution on health that can inform policy decisions, while providing a comprehensive and publicly available resource for future studies on both exposure and health effects. In this commentary, we discuss the motivation, rationale, and vision for our consortium and a path forward for reducing the enormous burden of disease from air pollution in India.
Rapid Generation of Leukemogenic Chromosomal Translocations in Vivo Using CRISPR/Cas9
Authors: Huang Yun , Marovca Blerim , Dettwiler Susanne , Bode Peter Karl , Bornhauser Beat , Bourquin Jean‐Pierre
Published: October 2020

Supplemental Digital Content is available in the text
USING MICROPERIMETRY AND LOW-LUMINANCE VISUAL ACUITY TO DETECT THE ONSET OF LATE AGE-RELATED MACULAR DEGENERATION
Authors: Wu Zhichao , Luu Chi D. , Hodgson Lauren A. B. , Caruso Emily , Chen Fred K. , Chakravarthy Usha , Arnold Jennifer J. , Heriot Wilson J. , Runciman Jim , Guymer Robyn H. ,   for the LEAD Study Group
Published: October 2020

Purpose:

To evaluate the performance of microperimetry and low-luminance visual acuity for detecting late age-related macular degeneration (AMD) onset.

Methods:

Two hundred ninety-two individuals with bilateral large drusen in the Laser Intervention in the Early Stages of AMD study underwent best-corrected visual acuity, low-luminance visual acuity, and microperimetry testing as well as multimodal imaging to detect late (neovascular or atrophic) AMD onset. The performance of the change in the measurement from baseline of each of visual function test for detecting late AMD onset was compared.

Results:

The area under the receiver operating characteristic curve for detecting neovascular and atrophic AMD onset was not significantly different for low-luminance visual acuity (area under the receiver operating characteristic curve = 0.71 and 0.56, respectively) and microperimetry (area under the receiver operating characteristic curve = 0.82 and 0.62, respectively) compared with best-corrected visual acuity (area under the receiver operating characteristic curve = 0.57 and 0.56, respectively; P ≥ 0.126 for all). There was also only a fair degree of agreement between the three visual function measures for detecting the onset of neovascular and atrophic AMD (κ ≥ 0.24).

Conclusion:

Microperimetry, low-luminance visual acuity, and best-corrected visual acuity demonstrate limited performance for detecting the earliest onset of late AMD. It remains to be established whether they perform better than current methods designed to enable self-detection of neovascular AMD onset, such as Amsler grid testing.
Is Vertical Transmission of SARS-CoV-2 Infection Possible in Preterm Triplet Pregnancy? A Case Series
Authors: Alwardi Talal Hamood , Ramdas Vidya , Al Yahmadi Mohammed , Al Aisari Salima , Bhandari Satish , Saif Al Hashami Hilal , Al Jabri Amal , Manikoth Prakash , Malviya Manoj
Published: October 2020

There is limited data regarding the vertical transmission (VT) of severe acute respiratory syndrome-coronavirus-2 infection. We report the first case of VT in preterm triplet pregnancy, with all triplets positive for severe acute respiratory syndrome-coronavirus-2 at 20 hours and day 5 of life. This report reiterates the need for an expedited formulation of a simple, standardized, and reproducible international case definition and classification for VT.
Amlodipine/valsartan fixed-dose combination treatment in the management of hypertension: A double-blind, randomized trial
Authors: Wang Kang-Ling , Yu Wen-Chung , Lu Tse-Min , Chen Lung-Ching , Leu Hsin-Bang , Chiang Chern-En
Published: October 2020

Background:

To compare the fixed-dose combination (FDC) of amlodipine/valsartan 5/80 mg with valsartan 160 mg monotherapy for efficacy and safety in hypertensive patients.

Methods:

We designed this double-blind, randomized, and noninferiority trial in which patients with elevated systolic blood pressure (SBP) and/or diastolic blood pressure (DBP) were randomly assigned to receive amlodipine/valsartan 5/80 mg FDC or valsartan 160 mg monotherapy for 8 weeks. The primary endpoint was changes in office SBP and DBP from baseline to 8 weeks. Twenty-four-hour blood pressure (BP) and the incidence of adverse events were recorded.

Results:

A total of 42 patients underwent randomization. At 8 weeks, office SBP changes were –16.5 ± 15.5 mmHg (p < 0.001) with amlodipine/valsartan 5/80 mg FDC and –6.9 ± 11.4 mmHg (p = 0.012) with valsartan 160 mg monotherapy while corresponding changes in office DBP were –9.8 ± 7.7 mmHg (p < 0.001) and –2.5 ± 6.6 mmHg (p = 0.095), respectively. The between-group differences were –9.6 mmHg (95% CI, -18.1 to -1.1; p = 0.028) for SBP and –7.3 mmHg (95% CI, -11.8 to -2.8; p = 0.002) for DBP. Furthermore, reductions in both 24-hour SBP (–9.2 mmHg; 95% CI, -16.4 to -2.1; p = 0.013) and DBP (–4.6 mmHg; 95% CI, -9.2 to -0.1; p = 0.048) were consistently greater with amlodipine/valsartan 5/80 mg FDC than with valsartan 160 mg. Overall, 27 and 23 adverse events occurred in the amlodipine/valsartan 5/80 mg FDC group and in the valsartan 160 mg monotherapy group, respectively. The majority were mild and were not related to study medications. There were no significant differences in safety between two treatments.

Conclusion:

Efficacy of amlodipine/valsartan 5/80 mg FDC was superior to that of valsartan 160 mg monotherapy while both treatments were well-tolerated.
Examining Mother-Reported Poor Sleep and Blood Pressure in Black/African American Mother-Child Dyads
Authors: Robbins Rebecca , DiClemente Ralph J. , Ejikeme Chidera , Crusto Cindy A. , Taylor Jacquelyn Y.
Published: October 2020

Background

Poor sleep is a confirmed risk factor for hypertension (HTN), and Black/African American (AA) women have among the highest rates of HTN in the United States.

Objective

We examined the relationship between sleep and blood pressure (BP) among Black/AA mother-child dyads using data from the Intergenerational Impact of Genetic and Psychological Factors on Blood Pressure study.

Methods

Data for this study were derived from 250 Black/AA mother-child dyads from low-income neighborhoods, collected via 4 home visits over 2 years. Mothers reported poor sleep, including reports of sleeping worse than usual and nighttime awakenings. Recordings of BP were obtained for mother and child. Mother BP was scored as normal (<120/<80 mm Hg), elevated (120–129/<80 mm Hg), stage 1 HTN (130–139/80–89 mm Hg), or stage 2 HTN (systolic ≥140 or diastolic ≥90 mm Hg). Generalized linear models examined the relationships between mother-reported poor sleep variables and both mother and child BP. Adjusted models examining mother BP controlled for the mother's age, education, marital status, smoking, body mass index, and depression symptoms.

Results

In adjusted models, nighttime awakenings were associated with stage 2 HTN (b = 2.70, 95% confidence interval [CI], 0.54–4.86, P < .05). Compared with children whose mother who had normal BP, children whose mother had elevated BP had higher diastolic BP (b = 0.37; 95% CI, 0.19–0.54; P < .001). Mother elevated BP was associated with both child systolic BP (b = 2.49; 95% CI, 0.44–4.53; P < .05) and diastolic BP (b = 2.07; 95% CI, 0.39–3.76; P < .05). Mother stage 1 HTN was associated with both child systolic BP (b = 2.16; 95% CI, 0.29–4.03; P < .05) and diastolic BP (b = 3.91; 95% CI, 2.40–5.42; P < .001). We detected a significant interaction between mother stage 2 HTN and mother nighttime awakenings in predicting higher child diastolic BP (b = 8.16; 95% CI, 0.65–15.68; P < .05).

Conclusions

We found evidence for an association between mothers' nighttime awakenings and very high BP. Our study also illuminated a strong relationship between high mother BP and high child BP. Finally, our study found preliminary support for the potentially mediating role of mothers' nighttime awakenings in predicting the relationship between mother stage 2 HTN and child BP.
The Role of Social Capital and Welfare in Absenteeism Across 26 OECD Countries
Authors: Kwon Min Jung
Published: October 2020

Objectives:

This study attempted to investigate social contextual effect on the occurrence of workers’ absenteeism.

Methods:

Survey data on 30,913 wage workers in 26 countries were linked to the indicators for social capital and welfare from the national database. Multi-level logistic regression was used for analyses.

Results:

Employment contract, atypical work, physical and psycho-social working conditions (effort and reward), social capital and welfare significantly explained the differences in occurrence of absenteeism across countries. Analysis of cross-level interactions revealed that macro indicators related to social capital, and public social and health expenditure had moderating effects on the relation between individual-level factors and absenteeism.

Conclusion:

High level of public spending on welfare policies and social bonding decrease the risk of absenteeism caused by vulnerable working environments, but it also worsen gaps in coping capabilities of workers in non-permanent contract and atypical work pattern.
Predicting Recidivism for Acquired Cholesteatoma: Evaluation of a Current Staging System
Authors: Angeli Simon , Shahal David , Brown Clifford Scott , Herman Bjorn
Published: October 2020

Objective:

Assess the utility and prognostic capabilities of the European Academy of Otology and Neurotology (EAONO) and Japanese Otological Society (JOS) cholesteatoma classification system, specifically for retraction pocket cholesteatoma.

Study Design:

Retrospective.

Setting:

Tertiary referral hospital.

Patients:

Adults and children with retraction pocket cholesteatoma.

Interventions:

Primary and planned second-look tympanoplasty with mastoidectomy.

Main Outcome Measures:

Incidence of recurrent or residual cholesteatoma at planned second-look surgery. Independent variables of age, gender, size of canal defect, and mucosa status were assessed. Additionally, the cholesteatoma classification, stage, and extent according to the EAONO/JOS system were recorded during the primary surgery.

Results:

A total of 125 cases were included. Twelve (9.6%) cases had recidivism over an average time of 7.5 months: the recurrence rate was 4% (n = 5), residual rate was 5% (n = 6), and one patient had both recurrent and residual disease (0.8%). Residual cholesteatoma occurred more frequently in children (p = 0.04, RR = 7.9 [1.0, 63.6]). Supratubal recess (S1) disease was associated with both recurrent cholesteatoma (p = 0.04, RR = 5.9 [1.3, 27.2]) and recidivism (p = 0.01, RR = 4.2 [1.5, 11.9]). Larger canal defects also showed an association with residual disease (p = 0.017).

Conclusion:

Younger patients and those with large ear canal defects tend to have residual disease at second-look surgery. Supratubal recess disease is also associated with recurrence. Despite the utility of the EAONO/JOS classification and staging system for cholesteatoma description and type, the prognostic value remains uncertain.
A brief discussion of the benefit and mechanism of vitamin D supplementation on coronavirus disease 2019
Authors: Cereda Emanuele , Bogliolo Laura , de Stefano Ludovico , Caccialanza Riccardo
Published: October 2020

Purpose of review

Vitamin D exerts extraskeletal functions, including immunomodulatory activity, protection against respiratory tract infections and pleiotropic effects on the cardiovascular system. Since the outbreak of the coronavirus disease-2019 (COVID-19) pandemic, several articles have suggested the potential involvement of vitamin D in reducing the risk and severity of the disease.

Recent findings

Epidemiological and observational studies support the hypothesis of a protective role of vitamin D but most studies are retrospective or based on small samples. However, the pandemic progression and the increased knowledge on the pathogenesis of COVID-19 have challenged the first evidence, suggesting also potential negative consequences derived by adequate vitamin D status. A cautious interpretation of the significance of low vitamin D25OH levels is advisable. The balance between over-activation of innate immunity and the exhaustibility of the adaptive immune response still needs to be clarified. In addition, the modulation of endothelial function, the down-regulation of renin, angiotensin-converting-enzyme (ACE) and angiotensin genes and the up-regulation of ACE2 expression is still an area of research.

Speculative hypotheses and observational data have suggested a protective role of vitamin D in COVID-19. However, many unanswered questions remain, aberrant detrimental effects of adequate vitamin D25OH levels cannot be excluded and whether its adequacy may prevent the infection or improve clinical outcomes needs to be assessed by adequately sized and designed population-based studies and intervention trials.
Preexposure Prophylaxis Outcomes in an Urban Community in North Carolina: Discontinuation of Care and Sexually Transmitted Infections
Authors: Clement Meredith Edwards , Nicchitta Mira , Sun Ying , Ellis Alicia , Chakraborty Hrishikesh , McGee Kara , Eagle Cedar , Frye Justin , Taylor Destry , Okeke Nwora Lance , Johnston Barbara , Seña Arlene C. , McKellar Mehri
Published: October 2020

Background

Few studies have examined long-term outcomes among persons who initiate preexposure prophylaxis (PrEP) in the South, including PrEP discontinuation and sexually transmitted infection (STI) rates.

Methods

Care discontinuation (>6 months without a PrEP appointment) and incident STIs were evaluated for patients at 2 PrEP clinics in Durham, NC. We tested for predictors of discontinuation as a binary variable using logistic regression. Model covariates included age, race/ethnicity, sex, known HIV-positive partner, commercial sex work, men who have sex with men (MSM) versus not MSM, type of insurance, and clinic site. A similar analysis was completed for STI incidence, controlling for days in the study.

Results

Among 271 patients, mean age was 33.2 years, 46.9% were Black and 11.1% were Latino, 81.2% were MSM, and 32% were uninsured. Preexposure prophylaxis was discontinued in 47%, and another 11% had intermittent care. Sexually transmitted infection incidence was 45.4/100 person-years, and 5 patients were diagnosed with HIV at baseline or in follow-up. Men who have sex with men were less likely to discontinue PrEP relative to non-MSM (odds ratio [OR], 0.26; 95% confidence interval [CI], 0.10–0.64). Baseline STI was associated with a higher likelihood of incident STI (OR, 8.19; 95% CI, 3.69–19.21), whereas care discontinuation was associated with a lower likelihood of STI (OR, 0.28; 95% CI, 0.11–0.65).

Conclusions

Preexposure prophylaxis programs in the Southern United States are reaching uninsured and predominantly Black and Latino MSM, but discontinuation rates are high despite elevated rates of incident STI and HIV. Further work is required to elucidate causes of PrEP discontinuation and encourage persistence in care.
Which Device Is Favorable for Intubation Attempts of Pediatric Residents on Four Different Pediatric Airway Simulations?
Authors: Er Anıl , Çağlar Aykut , Çitlenbik Hale , Akgül Fatma , Ulusoy Emel , Ören Hale , Yιlmaz Durgül , Duman Murat
Published: October 2020

Objectives

Endotracheal intubation is an essential skill for the pediatric airway management. Although direct laryngoscopy (DL) is the standard method, several videolaryngoscopes (VLs) have been recently enhanced as an alternative especially for difficult intubations. We aimed to compare McGrath MAC (McG) and Storz C-MAC PM (ST) VLs with DL in terms of intubation success rate, time to intubation (TTI), and duration of obtaining glottis view of intubation attempts performed by pediatric residents on different pediatric airway manikins.

Methods

The pediatric residents with no experience in videolaryngoscopy were included. After a brief demonstration, intubation attempts with 3 randomly handled different devices with 6 different blades were performed on a child manikin, an infant manikin, a Pierre-Robin sequence infant manikin, and a child manikin with cervical immobilization sequentially.

Results

Fifty pediatric residents were enrolled. The attempts of DL on child manikin and attempts of all devices on child with cervical immobilization simulation were completely successful. For the attempts on both infant manikin and Pierre-Robin sequence infant manikin, the success rate of McG was significantly lower than ST and DL (P = 0.011 and P = 0.001). In the child manikin, McG and ST had prolonged TTI compared with DL (P = 0.016 and P = 0.001). For the child with cervical immobilization simulation, TTI of DL was significantly shorter than McG and ST (P = 0.011 and P = 0.001). Time to intubation of McG was significantly longer than DL and ST for the attempts on both 2 infant manikins. The rate of Cormack-Lehane grade I glottis view was similar for the attempts on both 2 child airway simulations. For infant manikin and Pierre-Robin sequence infant simulation, the rate of Cormack-Lehane grade I of ST was higher than attempts of DL and McG.

Conclusions

The attempts of pediatric residents on infant normal airway and Pierre-Robin sequence infant airway simulations resulted with enhanced glottis view by the utilization of Storz C-MAC PM, but both 2 VLs did not provide the improvement of intubation success rate and TTI compared with DL on these 4 different pediatric manikins. Further clinical studies of different VLs in different clinical courses are required for a reliable utilization in children.
Sarcopenia Aneurysm Scoring System Predicts Early and Midterm Mortality After Endovascular Repair for Abdominal Aortic Aneurysm
Authors: Ito Eisaku , Ohki Takao , Toya Naoki , Fukushima Soichiro , Murakami Yuri , Nakagawa Hikaru , Nishie Ryosuke , Misawa Takeyuki
Published: October 2020

Objective:

The objective of the study was to develop a better model of prediction after EVAR using the psoas muscle index (PMI).

Summary Background Data:

The Glasgow Aneurysm Score (GAS), the modified Leiden Score (mLS), the Comorbidity Severity Score (CSS), and the Euro Score (ES) are known prognostic scoring after EVAR. Similarly, sarcopenia measured by PMI has been reported to be an important predictor. This study investigated a new scoring system using PMI predicting short and midterm overall mortality after EVAR.

Methods:

Three hundred ten patients were retrospectively evaluated. The primary endpoint was all-cause death. One hundred three patients were assigned to the derivation cohort and 207 patients to the validation cohort.

Results:

The all-cause mortality rates were 8.8% at 1 year, 23.5% at 3 years, and 32.8% at 5 years. In a multivariate analysis, age, aneurysm diameter, eGFR, and PMI were associated with all-cause mortality in the derivation cohort. The SAS system was defined as the sum of the following factors: elderly (75 years), large aneurysm (65 mm), low eGFR (30 mL/min/1.73m2), and low PMI (males: 48.2 cm2/m2, females: 36.8 cm2/m2). We compared the SAS with the other prognostic scoring for 5-year mortality evaluating the area under the receiver operating characteristic curves in the validation cohort (GAS: 0.731, mLS: 0. 718, CSS: 0. 646, ES: 0.661, and SAS: 0.785, P = 0.013).

Conclusion:

We developed the SAS to predict all-cause mortality after elective EVAR and this scoring showed excellent predictive performance.
exRNA Signatures in Extracellular Vesicles and their Tumor-Lineage from Prostate Cancer
Authors: Dogra Navneet , Ahsen Mehmet E. , Kozlova Edgar EG , Chen Tzu-yi , Allette Kimaada , Olsen Reena , Han Dan , Kim Sung-Cheol , Gifford Stacey M. , Smith Joshua T. , Wunsch Benjamin H. , Weil Rachel , Bhatt Kamala , Yadav Kamlesh K. , Vlachos Konstantinos , Nair Sujit , Gordon Ronald E. , Smith Melissa , Sebra Robert P. , Margolin Adam , Sahoo Susmita , Tewari Ashutosh K. , Cordon-Cardo Carlos , Losic Bojan , Stolovitzky Gustavo
Published: October 2020

Circulating extracellular vesicles (EVs) present in the bodily fluids of patients with cancer may provide non-invasive access to the tumor tissue. Yet, the transcriptomic lineage of tumor-derived EVs before and after tumor-resection remains poorly understood. Here, we established 60 total small RNA-sequencing profiles from 17 aggressive prostate cancer (PCa) patient’s tumor and adjacent normal tissue, and EVs isolated from urine, serum, and cancer cell culture media. We interrogated the key satellite alteration in tumor-derived EVs and found that resection of tumor prostate tissue leads to differential expression of reactive oxygen species (ROS), P53 pathways, inflammatory/cytokines, oncogenes, and tumor suppressor genes in the EV nanosatellites. Furthermore, we provide a set of novel EV-specific RNA signature, which are present in cancer but are nonexistent in post-resection patients with undetectable cancer. Finally, using a de novo RNAseq assembly followed by characterization of the small RNA landscape, we found novel small RNA clusters (smRCs) in the EVs, which reside in the unannotated regions. Novel smRCs were orthogonally validated for their differential expression in the ‘biomarker discovery’ cohort using RT-qPCR. We demonstrate that circulating tumor EVs provide a glimpse of the tumor tissue biology, resolving a major bottleneck in the current liquid biopsy efforts. Secretory vesicles appear to be playing a key role in non-canonical Wnt signaling and miRNA pathways, similar to the circulating tumor cells (CTCs), hence, we propose that such vesicles be called circulating tumor extracellular vesicles (CTEVs).
Public Awareness and Attitude towards Counterfeit Medicines in Sudan: A cross-sectional study
Authors: Wagiella Wala W. , Shantier Shaza W. , Gadkariem Elrasheed A.
Published: October 2020

Background

Counterfeit medicines (CFMs) are a global problem with significant and well-documented consequences for global health and patient safety, including drug resistance and patient deaths. Reports of counterfeit pharmaceuticals in Africa indicate a wide variety of detrimental effects.

Objectives

The aim of the present study was to assess the extent, awareness and attitude of public in Sudan towards CFMs.

Methods

A cross-sectional study was conducted applying pretested and structured questionnaire. The awareness and attitude were assessed statistically and the association between those and different demographic characteristics was calculated using Fisher exact test and Spearman correlation.

Results

A total of 386 participants have enrolled in the study. The majority of the respondents (58%) were found to be aware about the term CFMs with social media mentioned to be the main source. 73% of the respondents considered CFMs of worse quality suggesting getting the medicine from a trustworthy pharmacist in order to avoid buying CFMs. 56% reported their ability to distinguish CFMs from the side effects rather than the package and cost. Education was suggested by 82% of the respondents to have vital role in combating CFMs spread through workshops and campaigns. 68% of the participants were found to have a fair awareness about CFMs. Furthermore, 80% of them showed a good attitude toward CFMs

Conclusion

Current literature includes gaps in knowledge and attitude towards CFMs. Therefore attention and concentrated efforts are required on the part of the government, drug manufacturers and health care providers’ especially pharmaceutical analysts to ensure that only drugs of acceptable quality reach the patient.
Mitigating the transmission of infection and death due to SARS-CoV-2 through non-pharmaceutical interventions and repurposing drugs
Authors: Mondal Chittaranjan , Adak Debadatta , Majumder Abhijit , Bairagi Nandadulal
Published: October 2020

The Covid-19 pandemic has put the world under immeasurable stress. There is no specific drug or vaccine that can cure the infection or protect people from the infection of coronavirus. It is therefore prudent to use the existing resources and control strategies in an optimal way to contain the virus spread and provide the best possible treatments to the infected individuals. Use of the repurposing drugs along with the non-pharmaceutical intervention strategies may be the right way for fighting against the ongoing pandemic. It is the objective of this work to demonstrate through mathematical modelling and analysis how and to what extent such control strategies can improve the overall Covid-19 epidemic burden. The criteria for disease elimination & persistence were established through the basic reproduction number. A case study with the Indian Covid-19 epidemic data is presented to visualize and illustrate the personal hygiene & safe distancing, and repurposing drugs. It is shown that India can significantly improve the overall Covid-19 epidemic burden through the combined use of NPIs and repurposing drugs though containment of spreading is difficult without serious community participation.
Connecting structure and function from organisms to molecules in small animal symbioses through chemo-histo-tomography
Authors: Geier Benedikt , Oetjen Janina , Ruthensteiner Bernhard , Polikarpov Maxim , Gruber-Vodicka Harald , Liebeke Manuel
Published: October 2020

Our understanding of metabolic interactions between small symbiotic animals and bacteria or parasitic eukaryotes that reside within their body is extremely limited. This gap in knowledge originates from a methodological challenge, namely to connect histological changes in host tissues induced by beneficial and parasitic (micro)organisms to the underlying metabolites. To close this gap, we developed chemo-histo-tomography (CHEMHIST), a culture-independent approach to connect anatomic structure and metabolic function in millimeter-sized symbiotic animals. CHEMHIST combines spatial metabolomics based on mass spectrometry imaging (MSI) and microanatomy-based micro-computed X-ray tomography (microCT) on the same animal. Both high-resolution MSI and microCT allowed us to correlate the distribution of metabolites to the same animal’s three-dimensional (3D) histology down to sub-micrometer resolutions. Our protocol is compatible with tissue specific DNA sequencing and fluorescence in situ hybridization (FISH) for the taxonomic identification and localization of the associated micro(organisms). Building CHEMHIST upon in situ imaging, we sampled an earthworm from its natural habitat and created an interactive 3D model of its physical and chemical interactions with bacteria and parasitic nematodes in its tissues. Combining MSI and microCT, we introduce a workflow to connect metabolic and anatomic phenotypes of small symbiotic animals that often represent keystone species for ecosystem-functioning.

Significance

Metabolites mediate the establishment and persistence of most inter-kingdom symbioses. Still, to pinpoint the metabolites each partner displays upon interaction remains the biggest challenge in studying multi-organismal assemblages. Addressing this challenge, we developed a correlative imaging workflow to connect the in situ production of metabolites with the organ-scale and cellular 3D distributions of mutualistic and pathogenic (micro)organisms in the same host animal. Combining mass spectrometry imaging and micro-computed X-ray tomography provided a culture-independent approach, which is essential to include the full spectrum of naturally occurring interactions. To introduce the potential of combining high-resolution tomography with metabolite imaging, we resolve the metabolic interactions between an invertebrate host, its symbiotic bacteria and tissue parasites at unprecedented detail for model and non-model symbioses.
Boolean Implication Analysis Improves Prediction Accuracy of In Silico Gene Reporting of Retinal Cell Types
Authors: Subramanian Rohan , Sahoo Debashis
Published: October 2020

The retina is a complex tissue containing multiple cell types that is essential for vision. Understanding the gene expression patterns of various retinal cell types has potential applications in regenerative medicine. Retinal organoids (optic vesicles) derived from pluripotent stem cells have begun to yield insights into the transcriptomics of developing retinal cell types in humans through single cell RNA-sequencing studies. Previous methods of gene reporting have relied upon techniques in vivo using microarray data, or correlational and dimension reduction methods for analyzing single cell RNA-sequencing data in silico. Here, we present a bioinformatic approach using Boolean implication to discover retinal cell type-specific genes. We apply this approach to previously published retina and retinal organoid datasets and improve upon previously published correlational methods. Our method improves the prediction accuracy and reproducibility of marker genes of retinal cell types and discovers several new high confidence cone and rod-specific genes. Furthermore, our method is general and can impact all areas of gene expression analyses in cancer and other human diseases.

Significance Statement

Efforts to derive retinal cell types from pluripotent stem cells to the end of curing retinal disease require robust characterization of these cell types’ gene expression patterns. The Boolean method described in this study improves prediction accuracy of earlier methods of gene reporting, and allows for the discovery and validation of retinal cell type-specific marker genes. The invariant nature of results from Boolean implication analysis can yield high-value molecular markers that can be used as biomarkers or drug targets.
I-CONVEX: Fast and Accuratede NovoTranscriptome Recovery from Long Reads
Authors: Baharlouei Sina , Razaviyayn Meisam , Tseng Elizabeth , Tse David
Published: October 2020

Long-read sequencing technologies demonstrate high potential forde novodiscovery of complex transcript isoforms, but high error rates pose a significant challenge. Existing error correction methods rely on clustering reads based on isoform-level alignment and cannot be efficiently scaled. We propose a new method, I-CONVEX, that performs fast, alignment-free isoform clustering with almost linear computational complexity, and leads to better consensus accuracy on simulated, synthetic, and real datasets.
Exploring the niche ofRickettsia montanensis(Rickettsiales: Rickettsiaceae) infection of the American dog tick (Acari: Ixodidae), using multiple species distribution model approaches
Authors: Lippi Catherine A. , Gaff Holly D. , White Alexis L. , John Heidi K. St. , Richards Allen L. , Ryan Sadie J.
Published: October 2020

The American dog tick,Dermacentor variabilis(Say), is a vector for several human disease causing pathogens such as tularemia, Rocky Mountain spotted fever, and the understudied spotted fever group rickettsiae (SFGR) infection caused byRickettsia montanensis. It is important for public health planning and intervention to understand the distribution of this tick and pathogen encounter risk. Risk is often described in terms of vector distribution, but greatest risk may be concentrated where more vectors are positive for a given pathogen. When assessing species distributions, the choice of modeling framework and spatial layers used to make predictions are important. We first updated the modeled distribution ofD. variabilisandR. montanensisusing MaxEnt, refining bioclimatic data inputs, and including soils variables. We then compared geospatial predictions from five species distribution modeling (SDM) frameworks. In contrast to previous work, we additionally assessed whether theR. montanensispositiveD. variabilisdistribution is nested within a larger overallD. variabilisdistribution, representing a fitness cost hypothesis. We found that 1) adding soils layers improved the accuracy of the MaxEnt model; 2) the predicted ‘infected niche’ was smaller than the overall predicted niche across all models; and 3) each model predicted different sizes of suitable niche, at different levels of probability. Importantly, the models were not directly comparable in output style, which could create confusion in interpretation when developing planning tools. The random forest (RF) model had the best measured validity and fit, suggesting it may be most appropriate to these data.