bluuebunny/crossref_metadata_2025_split huggingface dataset:
Linear polarization in gamma-ray burst prompt emission
Authors: Gill Ramandeep , Granot Jonathan , Kumar Pawan 
Published: October 2019

Abstract
Despite being hard to measure, GRB prompt γ-ray emission polarization is a valuable probe of the dominant emission mechanism and the GRB outflow’s composition and angular structure. During the prompt emission the GRB outflow is ultra-relativistic with Lorentz factors Γ ≫ 1. We describe in detail the linear polarization properties of various emission mechanisms: synchrotron radiation from different magnetic field structures (ordered: toroidal Btor or radial B∥, and random: normal to the radial direction B⊥), Compton drag, and photospheric emission. We calculate the polarization for different GRB jet angular structures (e.g. top-hat, Gaussian, power-law) and viewing angles θobs. Synchrotron with B⊥ can produce large polarizations, up to $25\%\lesssim \Pi \lesssim 45\%$, for a top-hat jet but only for lines of sight just outside (θobs − θj ∼ 1/Γ) the jet’s sharp edge at θ = θj. The same also holds for Compton drag, albeit with a slightly higher overall Π. Moreover, we demonstrate how Γ-variations during the GRB or smoother jet edges (on angular scales ≳ 0.5/Γ) would significantly reduce Π. We construct a semi-analytic model for non-dissipative photospheric emission from structured jets. Such emission can produce up to $\Pi \lesssim 15\%$ with reasonably high fluences, but this requires steep gradients in Γ(θ). A polarization of $50\%\lesssim \Pi \lesssim 65\%$ can robustly be produced only by synchrotron emission from a transverse magnetic field ordered on angles ≳ 1/Γ around our line of sight (like a global toroidal field, Btor, for 1/Γ < θobs < θj). Therefore, such a model would be strongly favored even by a single secure measurement within this range. We find that such a model would also be favored if $\Pi \gtrsim 20\%$ is measured in most GRBs within a large enough sample, by deriving the polarization distribution for our different emission and jet models.
Convergent Evolution of Hydrogenosomes from Mitochondria by Gene Transfer and Loss
Authors: Lewis William H , Lind Anders E , Sendra Kacper M , Onsbring Henning , Williams Tom A , Esteban Genoveva F , Hirt Robert P , Ettema Thijs J G , Embley T Martin 
Published: October 2019

AbstractHydrogenosomes are H2-producing mitochondrial homologs found in some anaerobic microbial eukaryotes that provide a rare intracellular niche for H2-utilizing endosymbiotic archaea. Among ciliates, anaerobic and aerobic lineages are interspersed, demonstrating that the switch to an anaerobic lifestyle with hydrogenosomes has occurred repeatedly and independently. To investigate the molecular details of this transition, we generated genomic and transcriptomic data sets from anaerobic ciliates representing three distinct lineages. Our data demonstrate that hydrogenosomes have evolved from ancestral mitochondria in each case and reveal different degrees of independent mitochondrial genome and proteome reductive evolution, including the first example of complete mitochondrial genome loss in ciliates. Intriguingly, the FeFe-hydrogenase used for generating H2 has a unique domain structure among eukaryotes and appears to have been present, potentially through a single lateral gene transfer from an unknown donor, in the common aerobic ancestor of all three lineages. The early acquisition and retention of FeFe-hydrogenase helps to explain the facility whereby mitochondrial function can be so radically modified within this diverse and ecologically important group of microbial eukaryotes.
DSS1 interacts with and stimulates RAD52 to promote the repair of DSBs
Authors: Stefanovie Barbora , Hengel Sarah R , Mlcouskova Jarmila , Prochazkova Jana , Spirek Mario , Nikulenkov Fedor , Nemecek Daniel , Koch Brandon G , Bain Fletcher E , Yu Liping , Spies Maria , Krejci Lumir 
Published: October 2019

Abstract
The proper repair of deleterious DNA lesions such as double strand breaks prevents genomic instability and carcinogenesis. In yeast, the Rad52 protein mediates DSB repair via homologous recombination. In mammalian cells, despite the presence of the RAD52 protein, the tumour suppressor protein BRCA2 acts as the predominant mediator during homologous recombination. For decades, it has been believed that the RAD52 protein played only a back-up role in the repair of DSBs performing an error-prone single strand annealing (SSA). Recent studies have identified several new functions of the RAD52 protein and have drawn attention to its important role in genome maintenance. Here, we show that RAD52 activities are enhanced by interacting with a small and highly acidic protein called DSS1. Binding of DSS1 to RAD52 changes the RAD52 oligomeric conformation, modulates its DNA binding properties, stimulates SSA activity and promotes strand invasion. Our work introduces for the first time RAD52 as another interacting partner of DSS1 and shows that both proteins are important players in the SSA and BIR pathways of DSB repair.
A retrospective, quantitative assessment of disease burden in patients with leptomeningeal metastases from non-small-cell lung cancer
Authors: Nevel Kathryn S , DiStefano Natalie , Lin Xuling , Skakodub Anna , Ogilvie Shahiba Q , Reiner Anne S , Pentsova Elena , Boire Adrienne 
Published: October 2019

Abstract

Background
Improvements in detection and molecular characterization of leptomeningeal metastasis from lung cancer (LC-LM) coupled with cerebrospinal fluid (CSF)-penetrating targeted therapies have altered disease management. A barrier to formal study of these therapies in LM is quantification of disease burden. Also, outcomes of patients with targetable mutations in LC-LM are not well defined. This study employs molecular and radiographic measures of LM disease burden and correlates these with outcome.

Methods
We reviewed charts of 171 patients with LC-LM treated at Memorial Sloan Kettering. A subset had MRI and CSF studies available. Radiographic involvement (n = 76) was scored by number of gadolinium-enhancing sites in 8 locations. CSF studies included cytopathology, circulating tumor cell (CTC) quantification (n = 16), and cell-free DNA (cfDNA) analysis (n = 21). Clinical outcomes were compared with Kaplan–Meier log-rank test and Cox proportional hazards methodologies.

Results
Median overall survival was 4.2 months (95% CI: 3.6–4.9); 84 patients (49%) harbored targetable mutations. Among bevacizumab-naïve patients with MRI and CSF cytology at time of LC-LM diagnosis, extent of radiographic involvement correlated with risk of death (hazard ratio [HR]: 1.16; 95% CI: 1.02–1.33; P = 0.03), as did CSF CTC (HR: 3.39, 95% CI: 1.01–11.37; P = 0.048) and CSF cfDNA concentration (HR: 2.58; 95% CI: 0.94–7.05; P = 0.06). Those without a targetable mutation were almost 50% more likely to die (HR: 1.49; 95% CI: 1.06–2.11; P = 0.02).

Conclusions
Extent of radiographic involvement and quantification of CSF CTC and cfDNA show promise as prognostic indicators. These findings support molecular characterization and staging for clinical management, prognostication, and clinical trial stratification of LC-LM.
82. First 5 Years of Experience with the Illinois Extensively Drug-Resistant Organism (XDRO) Registry and Implementation of Automated Alerting
Authors: Lin Michael Y , Tang Angela , Fealy Amy E , Gao Wei , Markovski George , Xiang Yingxu , Trick William 
Published: October 2019

Abstract

Background
The Illinois XDRO Registry was created in November 2013 as an information system for XDROs; currently, the registry includes carbapenem-resistant Enterobacteriaceae (CRE), carbapenemase-producing Pseudomonas aeruginosa, and Candida auris. All Illinois healthcare facilities can manually query the registry at the time of admission to assess patients’ prior colonization status. A subset of facilities, mainly hospitals, participate in the registry’s automated querying process; alerts are generated automatically and sent via email, page, or text to infection preventionists at the time of patient admission.

Methods
We assessed counts of XDRO report submissions and total queries (manual and automated) over time, by organism. Facilities achieved automated alerts by sending a near-real-time feed of inpatient admission data (patient name and date of birth) to Illinois Department of Public Health (IDPH) via one of the three connection types: direct (data sent directly to IDPH), vendor (data sent via vendor software), and syndromic surveillance (existing syndromic surveillance data adapted for registry).

Results
In total, 6,445 unique patients (11,258 total reports) from 213 facilities have been reported to the XDRO registry (counts by organism type, Table). The registry has been manually queried 39,678 times by 232 facilities. Seventy-five facilities have achieved automation of alerting; the types of data connections used were direct (N = 56), vendor (N = 18), and syndromic surveillance (N = 1). In total, 5,344 automated alerts have been sent for 1,555 unique patients. Automated alerts per month have increased over time (P < 0.001, Figure). Infection preventionists reported feedback on 3,008 CRE alerts via a website questionnaire; among 1176 first alerts/patient/facility, 49% of patients’ XDRO status were previously unknown to the facility, and 33% were not in contact precautions at the time of alert.

Conclusion
The XDRO registry, originally focused on CRE, successfully expanded to include emerging XDRO threats such as Candida auris and is poised for rapid response to emerging threats. The registry’s adaptable reporting structure and expanding automation have enabled it to deliver an increasing number of actionable infection-control alerts over time.

Disclosures
All Authors: No reported Disclosures.
88. Public Health Service (PHS) Increased-Risk Factors in Organ Donors: A Review of the OPTN Ad hoc Disease Transmission Advisory Committee (DTAC)
Authors: Vece Gabe , La Hoz Ricardo M , Wolfe Cameron R , Ward Emily G , Wood R Patrick , Strasfeld Lynne , Sawyer Rob , Rana Meenakshi , Marboe Charles , Malinis Maricar , Liliy Kathleen , Ho Sam , Florescu Diana F , Danziger-Isakov Lara , Bucio Jamie , Berry Gerald , Bag Remzi , Aslam Saima , Michaels Marian G 
Published: October 2019

Abstract

Background
In the United States, all deceased donors (DD) are evaluated for behavioral risk factors for human immunodeficiency virus (HIV), hepatitis B (HBV), and hepatitis C (HCV) infection during the past 12 months. DD with behavioral risk factors or hemodilution are designated as PHS increased risk donors (IRD). Since 2013, the number of IRD has increased from 13.4% of DD to 27% in 2018. Despite a low residual risk of disease transmission after a negative nucleic acid test for HIV/HBV/HCV, the considerable underutilization of IRD has driven an interest in revising the PHS IRD 2013 guidelines. The objective of this study was to describe the epidemiology of IRD with the goal of guiding policy change and maximize organ use.

Methods
This is a retrospective cohort study of DD during 2018. Characteristics of IRD were compared with non-IRD. A random 10% sample of IRD was selected for manual review of text narratives and donor questionnaires submitted by organ procurement organizations to determine specific PHS IRD factors. Categorical variables were compared using the χ 2 test and continuous variables were compared using a 2-sample t-test for independent samples.

Results
Among 10,721 DD in 2018, 2,904 were designated IRD (27.1%) with regional variability noted (Figure). Compared with non-IRD, IRD were younger (median age 35 vs. 45 years, P < 0.001) and more often died from drug intoxication (33.2 vs. 5.6%, P < 0.001). Hemodilution was found in 6.8% of all IRD and was the only factor for IRD designation in 60% of pediatric donors <12 years old. The random sample of IRD (N = 288) was similar to IRD population for age, gender, ethnicity, cause of death, and region of recovery (table). Descriptive analysis of the random sample showed that intravenous drug use was the most common behavioral risk factor (N = 124, 43.1%), followed by incarceration (N = 108, 37.5%). Most DD met only 1 criterion (N = 179, 62%); 21% met 2 criteria; and 17% had >3 criteria.

Conclusion
This study represents the most detailed description of PHS IRD factors since the adoption of the new guidelines in 2013. Understanding the prevalence of factors that lead to IRD designation will help inform future policy development, optimize safe DD use, and increase the number of transplants.

Disclosures
All Authors: No reported Disclosures.
842. Social Resistance Fuels Ebola Transmission in the Eastern Democratic Republic of Congo
Authors: Mian Qaasim , Masumbuko Claude Kasereka , Underschultz Jack , Hawkes Michael 
Published: October 2019

Abstract

Background
The second largest Ebola epidemic in history is currently raging in Eastern Democratic Republic of Congo (DRC). Stubbornly persistent Ebola transmission has been associated with social resistance, ranging from passive noncompliance to overt acts of aggression toward Ebola response teams.

Methods
We explored community resistance using focus group discussions and assessed the prevalence of resistant views using standardized questionnaires.

Results
Despite being generally cooperative and appreciative of the foreign-led Ebola response, focus group participants provided eyewitness accounts of aggressive resistance to control efforts, consistent with recent media reports. Mistrust of Ebola response teams was fueled by perceived inadequacies of the response effort (“herd medicine”), suspicion of mercenary motives, and violation of cultural burial mores (“makeshift plastic morgue”). Survey questionnaires found that the majority of respondents had compliant attitudes with respect to Ebola control. Nonetheless, 78/630 (12%) respondents believed that Ebola was fabricated and did not exist in the area, 482/630 (72%) were dissatisfied with or mistrustful of the Ebola response, 60/630 (9%) sympathized with perpetrators of overt hostility, and 102/630 (15%) expressed noncompliant intentions in the case of Ebola illness or death in a family member, including hiding from the health authorities, touching the body, or refusing an official burial team. Denial of the biomedical discourse and dissatisfaction/mistrust of the Ebola response were statistically significantly associated with indicators of social resistance.

Conclusion
We concluded that social resistance to Ebola control efforts was prevalent among focus group and survey participants. Mistrust, with deep political and historical roots in this area besieged by chronic violence and neglected by the outside world, may fuel social resistance. Resistant attitudes may be refractory to short-lived community engagement efforts targeting the epidemic but not the broader humanitarian crisis in Eastern DRC.

Disclosures
All Authors: No reported Disclosures.
855. Evolution of Group B Streptococcal Capsular Type V Invasive Infections in Neonates and Young Infants: A Whole Genome Sequencing Study
Authors: Flores Anthony R , Sanson Misu A , Shah Brittany J , Rench Marcia , Shelburne Samuel A , Shelburne Samuel A , Baker Carol J 
Published: October 2019

Abstract

Background
Since 1970 group B Streptococcus (GBS) has been a frequent cause of sepsis or meningitis in young infants. Capsular polysaccharide type V was first recognized in 1990 and has increased to the point where it now causes ~15% of GBS infections. GBS type V strains are almost entirely sequence type 1 (ST1) in adult infections. To understand the emergence of type V GBS, we compared infant strains before 1990 to more contemporary isolates from young infants and adults.

Methods
Thirty-five strains isolated from blood or CSF of infants <90 days of age (Houston, 1979–1996) were compared with the following previously sequenced type V, ST1 strains: (1) 14 from infant blood or CSF from Center for Disease Control and Prevention (CDC) (2015–2017), (2) 193 blood ST1 isolates from adults (Houston, 1992–2013), and (3) 516 invasive isolates from the CDC (2015–2017). Isolates were sequenced using an Illumina MiSeq instrument followed by molecular typing, antimicrobial resistance gene determination, and phylogenetic analysis. Antimicrobial susceptibility testing (AST) was performed using disk diffusion and E-test.

Results
The majority (29/35) of Houston young infant strains were ST1. Type V GBS strains isolated prior to 1990 were more likely to be of ST-2 or ST-26 (5/10) compared with those from 1990 or later (24/25 and 14/14 CDC infant invasive type V). Tetracycline resistance was identified in 83% (29/35) while macrolide resistance (MR) occurred in only 23% (8/35) of the strains. Compared with early neonatal isolates, MR was significantly more frequent among contemporary neonatal (12/14, 86%, P < 0.0001) and adult (502/710, 71%, P < 0.0001) ST1 GBS. Phylogenetic analysis showed two distinct clades defined, in part, by MR. A high-frequency MR (340/360, 94%) clade was defined by the presence of erm(B) on Tn3872 while the low-frequency MR clade (159/350, 45%) was more diverse in mobile elements contributing to MR. The majority (27/29) of early neonatal ST1 GBS strains were observed in the low-frequency MR clade.

Conclusion
Infant invasive disease due to type V GBS before 1990 consisted of more diverse STs but is now almost exclusively ST1. Differences in the frequency of MR between early neonatal and contemporary type V ST1 GBS suggest MR may, at least in part, have driven the expansion of type V ST1 GBS.

Disclosures
All Authors: No reported Disclosures.
883. Evidence from a Multistate Cohort: Enrollment in Affordable Care Act Qualified Health Plans Results in Viral Suppression
Authors: McManus Kathleen A , Christensen Bianca B , Nagraj V P , Rogawski McQuade Elizabeth T , Furl Renae , Yerkes Lauren , Swindells Susan , Weissman Sharon , Rhodes Anne , Targonski Paul V , Dillingham Rebecca 
Published: October 2019

Abstract

Background
In individual states, the Patient Protection and Affordable Care Act has been associated with improved viral suppression (VS) rates for AIDS Drug Assistance Program (ADAP) clients or low-income people living with HIV (PLWH). This study aims to assess whether this association is consistent in multiple states (Nebraska, South Carolina, Virginia).

Methods
The multistate cohort included ADAP clients who were eligible for ADAP-funded Qualified Health Plans (QHPs). Data were collected from 2014 through 2015. A log-binomial model was used to estimate the association of demographics (age, race/ethnicity, sex, AIDS, rurality, HIV risk factor, previous VS) and healthcare delivery factors (income, previous ADAP plan, previous HIV care engagement) with QHP enrollment prevalence and 1-year risk of VS.

Results
For the cohort (n = 7,800; 5% NE, 36% SC, 59% VA), 52% enrolled in ADAP-funded QHPs with enrollment ranging from 35% to 63% by state. Enrollment in ADAP-funded QHPs in 2015 was higher for those who had ADAP-funded QHPs in 2014 (adjusted prevalence ratio [aPR] 3.28; 95% confidence interval [CI] 3.21–3.35) and those who were engaged in care in 2014 (aPR 1.16; 95% CI 1.05–1.27), and it was lower for those with a rural residence (aPR 0.91; 95% CI 0.81–1.00). Of those who were consistently engaged in care (n = 4,597), as defined by one viral load in 2014 and one viral load in 2015 separated by at least 180 days, those who received medications from Direct ADAP had a VS rate of 80.2% and those with ADAP-funded QHPs had a VS rate of 86.0%. The number needed to enroll in ADAP-funded QHPs for an additional PLWH to achieve VS is 18. Those who achieved VS in 2014 (adjusted risk ratio [aRR] 1.39, 95% CI 1.30–1.48) and those who enrolled in QHPs in 2015 (aRR 1.06, 95% CI 0.99–1.13) were more likely to achieve/maintain VS.

Conclusion
Additional efforts should be made to reach rural PLWH for QHP enrollment. State ADAPs, especially those in the South and those in states without Medicaid expansion, should consider investing in purchasing QHPs for PLWH because increased enrollment could improve VS rates. This evidence-based intervention could be a part of “Ending the HIV Epidemic.” Once ADAP clients are enrolled in ADAP-funded QHPs, they stay enrolled, and QHP enrollment is associated with VS across states and demographic groups.

Disclosures
All Authors: No reported Disclosures.
884. Patient Adherence to Long-Acting Injectable Cabotegravir + Rilpivirine Through 48 Weeks of Maintenance Therapy in the Phase 3 ATLAS and FLAIR Studies
Authors: Teichner Paula , Cutrell Amy , D’Amico Ronald , Dorey David , Griffith Sandy , Harrington Conn M , Huang Jenny , Hudson Krischan J , Margolis David , Mrus Joseph , Polli Joseph , Spreen William , Williams Peter , Van Solingen-Ristea Rodica , Shaefer Mark S 
Published: October 2019

Abstract

Background
Cabotegravir (CAB) and rilpivirine (RPV) are under development as a novel long-acting (LA) regimen for maintenance of HIV virologic suppression. Pooled Week 48 data from pivotal Phase 3 trials demonstrated noninferiority of CAB LA + RPV LA vs. current antiretroviral regimen (CAR) on the primary endpoint, proportion of subjects with HIV-1 RNA ≥50 c/mL (1.9% and 1.7%, respectively). Adherence to dosing visits, use of oral dosing (bridging) to cover planned missed injections and injection tolerability were examined for subjects in the ATLAS and FLAIR studies.

Methods
Virologically suppressed subjects (HIV-1 RNA < 50 c/mL) were randomized to switch to CAB LA + RPV LA or to continue CAR. On-time injections occurred Q4 weeks within a +7-day dosing window of the projected dosing date. Adherence to LA therapy was calculated as the number of on-time injection visits divided by the number of expected dosing visits through Week 48. Injection visits outside the pre-specified window and missed injection visits with/without the use of oral dosing were quantified. Injection tolerability was assessed via adverse event reporting.

Results
A total of 14,682 injections of CAB and RPV were administered to 581 subjects during 6,920 injection visits. 98% of injection visits took place within the allowed ±7-day dosing window with 3,194 (46%) on the projected dosing date. Forty-six (<1%) injection visits were early and 106 (2%) were late. Oral bridging was used in 16 subjects overall; 8 planned missed injection visits were successfully covered, with no change to virologic suppression status. No subject with HIV-1 RNA ≥ 50 c/mL at Week 48 had missed/late injection visits. 25% (3,663/14,682) of injections were associated with local injection site reactions (ISRs). The most common ISR was pain (3,087/3,663 = 84%). Most ISRs were grade 1–2 (99%), short duration (median 3 days), with few associated discontinuations (<1%).

Conclusion
Subjects receiving CAB LA + RPV LA demonstrated high rates of adherence to injection visits through week 48, with 98% of injections occurring within the ±7-day dosing window. Oral bridging with CAB and RPV was an effective strategy for maintaining viral load suppression to cover missed injection visits. Injections were well-tolerated with few associated discontinuations.

Disclosures
All Authors: No reported Disclosures.