bluuebunny/crossref_metadata_2025_split huggingface dataset:
Are Nonsynonymous Transversions Generally More Deleterious than Nonsynonymous Transitions?
Authors: Zou Zhengting , Zhang Jianzhi 
Published: August 2020

AbstractIt has been suggested that, due to the structure of the genetic code, nonsynonymous transitions are less likely than transversions to cause radical changes in amino acid physicochemical properties so are on average less deleterious. This view was supported by some but not all mutagenesis experiments. Because laboratory measures of fitness effects have limited sensitivities and relative frequencies of different mutations in mutagenesis studies may not match those in nature, we here revisit this issue using comparative genomics. We extend the standard codon model of sequence evolution by adding the parameter η that quantifies the ratio of the fixation probability of transitional nonsynonymous mutations to that of transversional nonsynonymous mutations. We then estimate η from the concatenated alignment of all protein-coding DNA sequences of two closely related genomes. Surprisingly, η ranges from 0.13 to 2.0 across 90 species pairs sampled from the tree of life, with 51 incidences of η &lt; 1 and 30 incidences of η &gt;1 that are statistically significant. Hence, whether nonsynonymous transversions are overall more deleterious than nonsynonymous transitions is species-dependent. Because the corresponding groups of amino acid replacements differ between nonsynonymous transitions and transversions, η is influenced by the relative exchangeabilities of amino acid pairs. Indeed, an extensive search reveals that the large variation in η is primarily explainable by the recently reported among-species disparity in amino acid exchangeabilities. These findings demonstrate that genome-wide nucleotide substitution patterns in coding sequences have species-specific features and are more variable among evolutionary lineages than are currently thought.
Do Combination Antiretroviral Therapy Regimens for HIV Infection Feature Diverse T-Cell Phenotypes and Inflammatory Profiles?
Authors: Tincati Camilla , Mondatore Debora , Bai Francesca , d’Arminio Monforte Antonella , Marchetti Giulia 
Published: August 2020

AbstractImmune abnormalities featuring HIV infection persist despite the use of effective combination antiretroviral therapy (cART) and may be linked to the development of noninfectious comorbidities. The aim of the present narrative, nonsystematic literature review is to understand whether cART regimens account for qualitative differences in immune reconstitution. Many studies have reported differences in T-cell homeostasis, inflammation, coagulation, and microbial translocation parameters across cART classes and in the course of triple vs dual regimens, yet such evidence is conflicting and not consistent. Possible reasons for discrepant results in the literature are the paucity of randomized controlled clinical trials, the relatively short follow-up of observational studies, the lack of clinical validation of the numerous inflammatory biomarkers utilized, and the absence of research on the effects of cART in tissues. We are currently thus unable to establish if cART classes and regimens are truly accountable for the differences observed in immune/inflammation parameters in different clinical settings. Questions still remain as to whether an early introduction of cART, specifically in the acute stage of disease, or newer drugs and novel dual drug regimens are able to significantly impact the quality of immune reconstitution and the risk of disease progression in HIV-infected subjects.
A Systematic Review of Treatment and Outcomes of Pregnant Women With COVID-19—A Call for Clinical Trials
Authors: Pastick Katelyn A , Nicol Melanie R , Smyth Elizabeth , Zash Rebecca , Boulware David R , Rajasingham Radha , McDonald Emily G 
Published: August 2020

Abstract

Background
Data pertaining to COVID-19 in pregnancy are limited; to better inform clinicians, we collated data from COVID-19 cases during pregnancy and summarized clinical trials enrolling this population.

Methods
We performed a systematic literature review of PubMed/MEDLINE to identify cases of COVID-19 in pregnancy or the postpartum period and associated outcomes. We then evaluated the proportion of COVID-19 clinical trials (from ClinicalTrials.gov) excluding pregnant or breastfeeding persons (both through June 29, 2020).

Results
We identified 11 308 published cases of COVID-19 during pregnancy. Of those reporting disease severity, 21% (416/1999) were severe/critical. Maternal and neonatal survival were reassuring (98% [10 437/10 597] and 99% [1155/1163], respectively). Neonatal disease was rare, with only 41 possible cases of infection reported in the literature. Of 2351 ongoing COVID-19 therapeutic clinical trials, 1282 were enrolling persons of reproductive age and 65% (829/1282) excluded pregnant persons. Pregnancy was an exclusion criterion for 69% (75/109) of chloroquine/hydroxychloroquine, 80% (28/35) of lopinavir/ritonavir, and 48% (44/91) of convalescent plasma studies. We identified 48 actively recruiting or completed drug trials reporting inclusion of this population.

Conclusions
There are limited published reports of COVID-19 in pregnancy despite more than 14 million cases worldwide. To date, clinical outcomes appear reassuring, but data related to important long-term outcomes are missing or not yet reported. The large number of clinical trials excluding pregnant persons, despite interventions with safety data in pregnancy, is concerning. In addition to observational cohort studies, pregnancy-specific adaptive clinical trials could be designed to identify safe and effective treatments.
Impact of Pharmacy Type on HIV Viral Suppression: A Retrospective Cross-Sectional Cohort Study
Authors: Havens Joshua P , Sayles Harlan , Fadul Nada , Bares Sara H 
Published: August 2020

Abstract

Background
People with HIV (PWH) use various pharmacy types beyond traditional local pharmacies. Some specialized pharmacies offer additive adherence services such as refill reminders, expedited delivery, and adherence packaging.

Methods
This single-center, retrospective cohort study evaluated the impact of pharmacy type on the gain or loss of HIV viral suppression (VS; HIV RNA ≤50 copies/mL). Patients (≥19 years) were categorized by VS and pharmacy type: HIV-specialized (additive adherence/delivery services) vs traditional (without adherence/delivery services). Fisher exact tests examined the effect of pharmacy type on differences in VS between years, and logistic regression models identified possible predictors of gaining or losing VS.

Results
During 2017–2018, no differences were observed for the gain or loss of VS across pharmacy types (VS gain vs continued viremia, P = .393; VS loss vs continued VS, P = .064). Predictors for the gain of VS included antiretroviral therapy adherence as percentage of days covered (PDC; adjusted odds ratio [aOR], 1.05; P &lt; .001) and Federal Poverty Level 100%–138% (FPL; aOR, 0.17; P = .032). Predictors for the loss of VS included use of protease inhibitor (aOR, 2.85; P = .013), ≥1 other illicit substance including tobacco (aOR, 2.96; P = .024), PDC (aOR, 0.95; P &lt; .001), FPL 139%–200% (aOR, 0.09; P = .031), and CD4 &gt;200 cells/ccm (aOR, 0.19; P = .013).

Conclusions
The gain or loss of VS among PWH in this retrospective cohort was not impacted by pharmacy transitions within the 2-year study period. However, PDC, FPL, illicit substance use, protease inhibitor use, and CD4 &gt;200 cells/ccm were identified as factors associated with changes in VS.
The Clinical Impact of Rapid Molecular Microbiological Diagnostics for Pathogen and Resistance Gene Identification in Patients With Sepsis: A Systematic Review
Authors: D’Onofrio Valentino , Salimans Lene , Bedenić Branka , Cartuyvels Reinoud , Barišić Ivan , Gyssens Inge C 
Published: August 2020

Abstract
Fast microbiological diagnostics (MDx) are needed to ensure early targeted antimicrobial treatment in sepsis. This systematic review focuses on the impact on antimicrobial management and patient outcomes of MDx for pathogen and resistance gene identification compared with blood cultures. PubMed was searched for clinical studies using either whole blood directly or after short-term incubation. Twenty-five articles were retrieved describing the outcomes of 8 different MDx. Three interventional studies showed a significant increase in appropriateness of antimicrobial therapy and a nonsignificant change in time to appropriate therapy. Impact on mortality was conflicting. Length of stay was significantly lower in 2 studies. A significant decrease in antimicrobial cost was demonstrated in 6 studies. The limitations of this systematic review include the low number and observed heterogeneity of clinical studies. In conclusion, potential benefits of MDx regarding antimicrobial management and some patient outcomes were reported. More rigorous intervention studies are needed focusing on the direct benefits for patients.
GABAergic but not Antidepressant Medications Increase Risk for Clostridioides difficile Infection in a National Cohort of Veterans
Authors: Lalani Falak , Young Eric H , Panchal Rupesh M , Reveles Kelly R 
Published: August 2020

Abstract

Background
Clostridioides difficile infection (CDI) is primarily mediated by alterations in the host gut ecosystem. While antibiotic use is the primary risk factor for CDI, other medications that modulate the gut ecosystem, particularly those targeting the gut–brain axis, could impact CDI risk. This study aimed to investigate the association between recent antidepressant and gamma-aminobutyric acid (GABA)–ergic medication use with CDI risk in a national cohort of United States veterans.

Methods
This was a retrospective case–control study of patients seen in Veterans Health Administration facilities from October 2002 to September 2014. CDI and non-CDI control patients were propensity score matched 1:1 using a maximum caliper of 0.0001. Antidepressant and GABAergic medication use 90 days before cohort inclusion were analyzed for CDI association using bivariable and multivariable logistic regression models.

Results
A total of 85 831 patients were included, and 9287 CDI and 9287 control patients were propensity score matched. Antidepressant use overall was not significantly associated with CDI risk (odds ratio [OR], 1.05; 95% CI, 0.98–1.12), although GABAergic medication use was associated with increased risk (OR, 1.81; 95% CI, 1.70–1.92). In multivariable models of individual medications/classes, benzodiazepines had the strongest CDI association (OR, 1.91; 95% CI, 1.77–2.07). SSRIs (OR, 0.88; 95% CI, 0.81–0.95) and bupropion (OR, 0.67; 95% CI, 0.57–0.78) were negatively associated with CDI.

Conclusions
In this national study of veterans, GABAergic medication use was a positive predictor of CDI risk, though antidepressant use was not. Further research is needed to understand biological mechanisms, and confirmatory studies are needed to validate these findings.
Lower Mortality Associated With Adjuvant Corticosteroid Therapy in Non-HIV-Infected Patients With Pneumocystis jirovecii Pneumonia: A Single-Institution Retrospective US Cohort Study
Authors: Mundo William , Morales-Shnaider Louis , Tewahade Selam , Wagner Eric , Archuleta Solana , Bandali Mohamed , Chadalawada Sindhu , Johnson Steven C , Franco-Paredes Carlos , Shapiro Leland , Henao-Martínez Andrés F 
Published: August 2020

Abstract

Background
Pneumocystis jirovecii pneumonia (PJP) remains a cause of mortality in HIV-negative patients. The clinical benefit of adjuvant corticosteroids in these patients is uncertain. This study aimed to determine if corticosteroids would reduce mortality in a cohort of HIV-negative PJP patients.

Methods
We examined a retrospective case series of patients diagnosed with PJP at the University of Colorado Hospital between 1995 and 2019. Data were collected in 71 PJP-infected patients. Twenty-eight patients were HIV-negative, and 43 were infected with HIV. We performed bivariate and forward, stepwise multivariable logistic regressions to identify mortality predictors.

Results
Common underlying conditions in HIV-negative patients were hematologic malignancies (28.6%), autoimmune disorders (25.9%), and solid organ transplantation (10.7%). HIV-negative patients had higher rates and durations of mechanical ventilation and intensive care unit stay. Survival was significantly increased in HIV-negative patients receiving adjuvant corticosteroids, with 100% mortality in patients not receiving corticosteroids vs 60% mortality in patients receiving corticosteroids (P = .034). In an adjusted multivariable model, no adjuvant corticosteroid use was associated with higher mortality (odds ratio, 13.5; 95% CI, 1.1–158.5; P = .039) regardless of HIV status.

Conclusions
We found substantial mortality among HIV-negative patients with PJP, and adjuvant corticosteroid use was associated with decreased mortality. Response to corticosteroids is best established in HIV-infected patients, but emerging reports suggest a similar beneficial response in PJP patients without HIV infection. Further prospective studies may establish a more definitive role of the addition of corticosteroids among HIV-negative patients with PJP.
Identifying Enteropathogens in Children with Acute Gastroenteritis Presenting with Isolated Vomiting–Appetite Study
Authors: Lee Bonita , Pang Xiao-Li , Zhuo Ran , Parsons Brendon , Chui Linda , Xie Jianling , Lowerison Karen , Osterreicher Lara , Ali Samina , Freedman Stephen ,   APPETITE (Alberta Provincial Pediatric EnTeric Infection TEam)
Published: August 2020

Abstract

Background
As diarrheal stool samples are the recommended specimen for testing in acute gastroenteritis (AGE), etiological investigations are rarely performed in children presenting with isolated vomiting. This study identifies enteropathogens in children with AGE presenting with isolated vomiting.

Methods
Children &lt;18 years old with ≥3 episodes of vomiting/diarrhea in 24 hours and &lt;7 days of symptoms were recruited in 2 pediatric emergency departments, a public health clinic and via Health Link, a provincial nurse advice phone line. Rectal swabs and stool samples were collected and tested using the Luminex xTAG GPP, an in-house 5-virus RT-qPCR panel and enteric bacterial culture. Vomiting and diarrhea data were collected at enrollment (day 0) and at day 14.

Results
Between Dec 9, 2014 and Apr 14, 2016, 2,184 children were enrolled and tested: 784 (36%) presented with isolated vomiting, 250 (11%) with isolated diarrhea (ID), 1,138 (52%) with both vomiting and diarrhea (V&D), 12 had missing data. The detection of enteropathogens was 56% when presenting with isolated vomiting, 55% with ID and 83% with V&D. Of the 784 children with isolated vomiting, 54% (n = 424) had one or more viruses: the most common was norovirus (NoV) (n = 244, 50%), followed by adenovirus (Adv) (91, 19%), rotavirus (Rota) (57, 12%), sapovirus (84, 17%) and astrovirus (10, 2%). Fifty-eight cases had &gt;1 virus; co-infection with NoV and Adv was the most common (n = 23). Ten of these 424 patients also had enteric bacteria (2 Aeromonas, 2 ETEC, 2 Salmonella, 2 Yersinia, 1 Campylobacter, 1 E coli O157) and 8/9 (89%) of these patients reported development of diarrhea at day 14. In comparison, 212/383 (55%) of patients with virus only reported diarrhea at follow up. Enteric bacteria with no virus was detected in 11 patients (3 Aeromonas, 3 Salmonella, 3 STEC, 1 Campylobacter, 1 E coli O157) and 3/10 of these patients reported diarrhea.

Conclusion
Over 50% of AGE presented with isolated vomiting had enteric virus identified in stool or rectal swabs, representing a significant pathogen-based disease burden not previously included in healthcare planning (e.g., Rota vaccine). NoV was the predominant agent followed by Adv and Rota. Finding enteric bacteria in these cases is novel and requires further study.

Disclosures
All authors: No reported disclosures.
Small Airway Wall Thickening Assessed by Computerized Tomography Is Associated With Low Lung Function in Chinese Carbon Black Packers
Authors: Cao Xue , Lin Li , Sood Akshay , Ma Qianli , Zhang Xiangyun , Liu Yuansheng , Liu Hong , Li Yanting , Wang Tao , Tang Jinglong , Jiang Menghui , Zhang Rong , Yu Shanfa , Yu Zhiqiang , Zheng Yuxin , Han Wei , Leng Shuguang 
Published: August 2020

Abstract
Nanoscale carbon black as virtually pure elemental carbon can deposit deep in the lungs and cause pulmonary injury. Airway remodeling assessed using computed tomography (CT) correlates well with spirometry in patients with obstructive lung diseases. Structural airway changes caused by carbon black exposure remain unknown. Wall and lumen areas of sixth and ninth generations of airways in 4 lobes were quantified using end-inhalation CT scans in 58 current carbon black packers (CBPs) and 95 non-CBPs. Carbon content in airway macrophage (CCAM) in sputum was quantified to assess the dose-response. Environmental monitoring and CCAM showed a much higher level of elemental carbon exposure in CBPs, which was associated with higher wall area and lower lumen area with no change in total airway area for either airway generation. This suggested small airway wall thickening is a major feature of airway remodeling in CBPs. When compared with wall or lumen areas, wall area percent (WA%) was not affected by subject characteristics or lobar location and had greater measurement reproducibility. The effect of carbon black exposure status on WA% did not differ by lobes. CCAM was associated with WA% in a dose-dependent manner. CBPs had lower FEV1 (forced expiratory volume in 1 s) than non-CBPs and mediation analysis identified that a large portion (41–72%) of the FEV1 reduction associated with carbon black exposure could be explained by WA%. Small airway wall thickening as a major imaging change detected by CT may underlie the pathology of lung function impairment caused by carbon black exposure.
Capital Allocation in Developing Countries
Authors: David Joel M , Venkateswaran Venky , Cusolito Ana Paula , Didier Tatiana 
Published: August 2020

Abstract
This paper investigates the sources of capital misallocation across a group of developing and developed countries, using the empirical methodology developed in David and Venkateswaran (2019. “The Sources of Capital Misallocation.” American Economic Review 109 (7): 2531–67). The main findings are: (i) technological frictions—namely, adjustment costs and uncertainty—account for only a modest share of the observed misallocation; (ii) heterogeneity in firm-level technologies potentially explains between one-quarter and one-half, but (iii) dispersion in markups is much smaller; (iv) after accounting for these factors, on average, at least 50 percent of misallocation within each country remains unexplained, suggesting a large role for additional—potentially distortionary—factors. These factors are largely attributable to a component that is correlated with firm size/productivity and one that is essentially permanent to the firm. They exhibit strong negative correlations with income per capita and direct measures of the quality of the business environment from the World Bank Doing Business Report. The paper reports a broad set of moments describing firm-level investment dynamics and detailed parameter estimates on a country-by-country basis with an eye towards future work in this area.
IMPACT OF CORONAVIRUS DISEASE PANDEMIC ON INTRAVITREAL INJECTIONS TREATMENT FOR MACULAR DISEASES
Authors: Viola Francesco , Milella Paolo , Pozzo Giuffrida Francesco , Ganci Simone , Invernizzi Alessandro 
Published: August 2020

Purpose:
To describe our managing strategy for COVID-19 emergency, to evaluate the adherence to intravitreal treatment (AtT) rate during the outbreak in a referral hospital in Milan, and to correlate it with patients' clinical features.

Methods:
The AtT rate of patients with scheduled intravitreal injections during the COVID-19 outbreak from February 23, 2020 to March 31, 2020 was compared with the previous trimester and with March 2019. The impact of age, sex, visual function, and diagnosis on the AtT rate during unlocked/locked weeks (from March 8th) was evaluated.

Results:
Of 650 consecutive patients with scheduled intravitreal injections, the AtT rate during the COVID-19 outbreak was 0.37. This was significantly lower compared with AtT registered in the previous trimester (0.92) and in the same weeks in 2019 (0.90) (both P < 0.001). Patients adherent to treatment were significantly younger (P < 0.001) and had a lower best-corrected visual acuity in the fellow eye (P = 0.046). During the lockdown weeks, the AtT rate was significantly lower than in the two unlocked weeks (0.19 vs. 0.73, P < 0.001). In addition, the AtT rate in patients classified as “emergent” during the lockdown weeks was 0.60.

Conclusion:
These preliminary results can help the retina specialist community to foresee this unique scenario and to develop successful management strategies.
REVIEW OF OPHTHALMIC AND BREASTFEEDING MEDICINE EVIDENCE
Authors: Dalal Prarthana J. , Patel Aloka L. , Carle Michelle , Rajanala Alekya , Gill Manjot K. 
Published: August 2020

Background/Purpose:There is limited research regarding the consequences of treating lactating mothers with intravitreal anti–vascular endothelial growth factor (VEGF) agents. Balancing the need for vision-saving treatment, the benefits of breastfeeding, and the concern for affecting the newborn can present a conflict for both mothers and ophthalmologists. This review summarizes the state of the literature regarding the use of intravitreal anti-VEGF agents during breastfeeding along with details about their pharmacology.Results:Bevacizumab and aflibercept have Fc domains subjecting them to FcRn recycling and extending their half-life compared with ranibizumab which is an antibody fragment and lacks the Fc domain. Case reports and small studies have shown that ranibizumab has the lowest serum concentration after intravitreal injection and the least effect on plasma-free VEGF concentrations and breastmilk VEGF levels.Conclusion:Clinical and pharmacologic data suggest that ranibizumab has less systemic circulation and effect on maternal serum and breastmilk VEGF levels when compared to bevacizumab and aflibercept. However, there is significant need for further research on the degree and duration to which intravitreal agents circulate systemically, what fraction is transferred into breastmilk and is absorbed, and whether this results in any functional adverse effects to the infant. Other factors to consider in the medical decision-making of lactating mothers necessitating intravitreal anti-VEGF treatment include the gestational and post-natal age of the child and whether it is feasible to avoid breastfeeding for the half-life duration of the intravitreal agent rather than ceasing breastfeeding altogether.