bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cost-related Medication Nonadherence and Its Risk Factors Among Medicare Beneficiaries
Authors: Nekui Farrah , Galbraith Alison A. , Briesacher Becky A. , Zhang Fang , Soumerai Stephen B. , Ross-Degnan Dennis , Gurwitz Jerry H. , Madden Jeanne M. 
Published: December 2020

Background:
Unaffordability of medications is a barrier to effective treatment. Cost-related nonadherence (CRN) is a crucial, widely used measure of medications access.

Objectives:
Our study examines the current national prevalence of and risk factors for CRN (eg, not filling, skipping or reducing doses) and companion measures in the US Medicare population.

Research Design:
Survey-weighted analyses included logistic regression and trends 2006–2016.

Subjects:
Main analyses used the 2016 Medicare Current Beneficiary Survey. Our study sample of 12,625 represented 56 million community-dwelling beneficiaries.

Measures:
Additional outcome measures were spending less on other necessities in order to pay for medicines and use of drug cost reduction strategies such as requesting generics.

Results:
In 2016, 34.5% of enrollees under 65 years with disability and 14.4% of those 65 years and older did not take their medications as prescribed due to high costs; 19.4% and 4.7%, respectively, experienced going without other essentials to pay for medicines. Near-poor older beneficiaries with incomes $15–25K had 50% higher odds of CRN (vs. >$50K), but beneficiaries with incomes <$15K, more likely to be eligible for the Part D Low-Income Subsidy, did not have significantly higher risk. Three indicators of worse health (general health status, functional limits, and count of conditions) were all independently associated with higher risk of CRN.

Conclusions:
Changes in the risk profile for CRN since Part D reflect the effectiveness of targeted policies. The persistent prevalence of CRN and associated risks for sicker people in Medicare demonstrate the consequences of high cost-sharing for prescription fills.
Head-to-head comparison of SARS-CoV-2 antigen-detecting rapid test with professional-collected nasal versus nasopharyngeal swab
Authors: Lindner Andreas K. , Nikolai Olga , Rohardt Chiara , Burock Susen , Hülso Claudia , Bölke Alisa , Gertler Maximilian , Krüger Lisa J. , Gaeddert Mary , Tobian Frank , Lainati Federica , Seybold Joachim , Jones Terry C. , Hofmann Jörg , Sacks Jilian A. , Mockenhaupt Frank P. , Denkinger Claudia M. 
Published: December 2020

AbstractBackgroundNasopharyngeal (NP) swab samples for antigen-detecting rapid diagnostic tests (Ag-RDTs) require qualified healthcare professionals and are frequently perceived as uncomfortable by patients.MethodsWe performed a manufacturer-independent, prospective diagnostic accuracy study, comparing professional-collected nasal mid-turbinate (NMT) to nasopharyngeal swab, using the test kits of a WHO-listed SARS-CoV-2 Ag-RDT (STANDARD Q COVID-19 Ag Test, SD Biosensor), which is also being distributed by Roche. Individuals with high suspicion for COVID-19 infection were tested. The reference standard was RT-PCR using a combined oro-/nasopharyngeal swab sample. Percent positive and negative agreement, as well as sensitivity and specificity were calculated.ResultsAmong the 179 participants, 41 (22.9%) tested positive for SARS-CoV-2 by RT-PCR. The positive percent agreement of the two different sampling techniques for the Ag-RDT was 93.5% (CI 79.3-98.2). The negative percent agreement was 95.9% (CI 91.4-98.1). The Ag-RDT with NMT-sampling showed a sensitivity of 80.5% (33/41 PCR positives detected; CI 66.0-89.8) and specificity of 98.6% (CI 94.9-99.6) compared to RT-PCR. The sensitivity with NP-sampling was 73.2% (30/41 PCR positives detected; CI 58.1-84.3) and specificity was 99.3% (CI 96.0-100). In patients with high viral load (>7.0 log10 SARS-CoV-2 RNA copies/swab), the sensitivity of the Ag-RDT with NMT-sampling was 100% and 94.7% with NP-sampling.ConclusionThis study demonstrates that sensitivity of a WHO-listed SARS-CoV-2 Ag-RDT using a professional nasal-sampling kit is at least equal to that of the NP-sampling kit, although confidence intervals overlap. Of note, differences in the IFUs of the test procedures could have contributed to different sensitivities. NMT-sampling can be performed with less training, reduces patient discomfort, and it enables scaling of antigen testing strategies. Additional studies of patient self-sampling should be considered to further facilitate the scaling-up of Ag-RDT testing.
A novel homozygous missense mutation p.P388S in TULP1 causes protein instability and retinitis pigmentosa
Authors: Woodard DaNae R. , Xing Chao , Ganne Pratyusha , Liang Hanquan , Mahindrakar Avinash , Sankurathri Chandrasekhar , Hulleman John D. , Mootha V. Vinod 
Published: December 2020

ABSTRACTPurposeRetinitis pigmentosa (RP) is an inherited retinal disorder that results in the degeneration of photoreceptor cells, ultimately leading to severe visual impairment. We characterized a consanguineous family from Southern India wherein an individual in his 20’s presented with night blindness since childhood. The purpose of this study was to identify the causative mutation for RP in this individual as well as characterize how the mutation may ultimately affect protein function.MethodsWe performed a complete ophthalmologic examination of the proband followed by exome sequencing. The identified mutation was then modeled in cultured cells, evaluating its expression, solubility (both by western blot), subcellular distribution (confocal microscopy), and testing whether this variant induced endoplasmic reticulum (ER) stress (qPCR and western blotting).ResultsThe proband presented with generalized and parafoveal retinal pigment epithelial atrophy with bone spicule pigmentation in the mid periphery and arteriolar attenuation. Optical coherence tomography scans through the macula of both eyes showed atrophy of outer retinal layers with loss of the ellipsoid zone, whereas systemic examination of this individual was normal. The proband’s parents and sibling were asymptomatic and had normal funduscopic examinations. We discovered a novel homozygous p.Pro388Ser mutation in the tubby-like protein 1 (TULP1) gene in the individual with RP. In cultured cells, the P388S mutation does not alter the subcellular distribution of TULP1 or induce ER stress when compared to wild-type TULP1, but instead significantly lowers protein stability as indicated by steady-state and cycloheximide-chase experiments.ConclusionsThese results add to the list of known TULP1 mutations associated with RP and suggest a unique pathogenic mechanism in TULP1-induced RP, which may be shared amongst select mutations in TULP1.
Does HIV impact susceptibility to COVID-19 (SARS-CoV-2) infection and pathology? A review of the current literature
Authors: Aghakishiyeva Elnara , Macallan Derek 
Published: December 2020

AbstractObjectivesGiving appropriate guidance to people living with HIV (PLWH) during the COVID-19 pandemic depends on having adequate data to inform recommendations. Several studies have now been published which inform such advice. The objective of this study was to collate this information and review the implications of emerging data.MethodsWe performed a systematic literature search of studies relating COVID-19 to HIV infection from the beginning of the pandemic to end of November 2020. We included both published and pre-published manuscripts and analysed papers according to whether they primarily informed risk of infection or risk of adverse outcome.Results68 papers (including 11 pre-prints) were identified. In terms of risk of infection, it appears that PLWH are no more or less likely to become infected with COVID-19. In terms of outcomes and mortality, most early small studies did not demonstrate an increase in mortality compared to background populations. However, several larger, more recent studies from South Africa, New York and two from the UK demonstrate higher mortality among PLWH when results are adjusted for other risk factors, giving relative risks of 2.1, 1.2, 1.7 and 2.3 respectively. Apparently conflicting results may arise from differences between studies in their power to account for cofactors and confounding variables. HIV-positive non-survivors tend to be younger and have fewer comorbidities than their HIV-negative counterparts; mortality may be higher in PLWH with low CD4 counts.ConclusionsAlthough the literature appears conflicting, large studies which account for covariates strongly suggest that HIV infection increases COVID-19 mortality.
Sensitive detection and quantification of SARS-CoV-2 in saliva
Authors: Abasiyanik Mustafa Fatih , Flood Blake , Lin Jing , Ozcan Sefika , Rouhani Sherin J , Pyzer Athalia , Trujillo Jonathan , Zhen Chaojie , Wu Ping , Jumic Stephen , Wang Andrew , Gajewski Thomas F. , Wang Peng , Hartley Madeline , Ameti Bekim , Niemiec Rachael , Fernando Marian , Aydogan Bulent , Bethel Cindy , Matushek Scott , Beavis Kathleen G. , Agrawal Nishant , Segal Jeremy , Tay Savaş , Izumchenko Evgeny 
Published: December 2020

AbstractSaliva has significant advantages as a test medium for detection of SARS-CoV-2 infection in patients, such as ease of collection, minimal requirement of supplies and trained personnel, and safety. Comprehensive validation in a large cohort of prospectively collected specimens with unknown SARS-CoV-2 status should be performed to evaluate the potential and limitations of saliva-based testing. We developed a saliva-based testing pipeline for detection of SARS-CoV-2 nucleic acids using real-time reverse transcription PCR (RT-PCR) and droplet digital PCR (ddPCR) readouts, and measured samples from 137 outpatients tested at a curbside testing facility and 29 inpatients hospitalized for COVID-19. These measurements were compared to the nasal swab results for each patient performed by a certified microbiology laboratory. We found that our saliva testing positively detects 100% (RT-PCR) and 93.75% (ddPCR) of curbside patients that were identified as SARS-CoV-2 positive by the Emergency Use Authorization (EUA) certified nasal swab testing assay. Quantification of viral loads by ddPCR revealed an extremely wide range, with 1 million-fold difference between individual patients. Our results demonstrate for both community screening and hospital settings that saliva testing reliability is on par with that of the nasal swabs in detecting infected cases, and has potential for higher sensitivity when combined with ddPCR in detecting low-abundance viral loads that evade traditional testing methods.
At-home self-testing of teachers with a SARS-CoV-2 rapid antigen test to reduce potential transmissions in schools
Authors: Hoehl Sebastian , Schenk Barbara , Rudych Olga , Göttig Stephan , Foppa Ivo , Kohmer Niko , Karaca Onur , Toptan Tuna , Ciesek Sandra 
Published: December 2020

AbstractBackgroundRapid antigen tests for SARS-CoV-2 became available recently, offering an opportunity to vastly increase testing capacities. Antigen tests offer lower sensitivity than the gold standard, RT-PCR, but rapid sample-to-answer time. High-frequency testing with an antigen test may offset the lower sensitivity, and testing can be done with at-home collection of samples, offering potential benefit in screening efforts. In this study, we set out to evaluate the practical application of self-performed high-frequency antigen test in a school setting.MethodA total of 711 teachers from 86 schools were enrolled in a seven-week study. After instruction, participants tested themselves every 48 hours at home with a rapid antigen test for SARS-CoV-2 (target: nucleocapsid protein) in a self-collected anterior nasal swab. Positive results in the antigen test were confirmed via RT-PCR from the same sample that had been determined to be positive by the study participant. A questionnaire was given to all participants to evaluate whether the test failed to detect infection.Findings10 836 tests from 602 teachers were recorded and analyzed. A total of five confirmed cases of viral shedding of SARS-CoV-2 was detected by use of the antigen test. One study participant with a SARS-CoV-2 infection was presymptomatic and four were mildly symptomatic at the time of the antigen test. Sixteen false positive antigen tests (0.15% of all tests) were reported, predominantly when the local incidence in the general population was low. In four cases, the study participant reported that a PCR had detected a SARS-CoV-2 infection, but the antigen test was negative, indicating a false negative result.InterpretationHigh-frequency, self-performed rapid antigen tests can detect individuals with a SARS-CoV-2 infection, and therefore potentially reduce transmissions. Testing may be most beneficial when applied during high local incidence of SARS-CoV-2 infections and when mild or atypical symptoms are present. To avoid a high rate of false positive results, a test with optimized specificity should be used.FundingThe study was commissioned and funded by the Hessian Ministry of Education and the Hessian Ministry of Integration and Social Affairs.
A Mendelian randomisation study of smoking causality in IPF compared with COPD
Authors: Duckworth Anna , Gibbons Michael A. , Beaumont Robin N , Wood Andrew R , Almond Howard , Lunnon Katie , Lindsay Mark A. , Scotton Chris J , Tyrrell Jess 
Published: December 2020

AbstractIn a normal year, the fatal lung disease Idiopathic Pulmonary Fibrosis (IPF) accounts for ∼1% of UK deaths. Smoking is a recognised risk factor for IPF but the question of causality remains unanswered. Here, we used data from the UK Biobank (UKBB) and the well-established genetic technique of Mendelian randomisation (MR) methods to investigate whether smoking is causal for IPF compared with COPD, where causality is established.We looked at observational associations in unrelated Europeans, with 871 IPF cases, 11,413 COPD cases and 366,942 controls. We performed analyses using one-sample MR to test for inferred smoking causality in ever smokers using genetic variants that have a previously demonstrated association with smoking heaviness.Strong associations between disease status and ever having smoked were found in both IPF (OR = 1.52; 95%CI:1.32-1.74; P=2.4×10−8) and COPD (OR= 5.77; 95%CI:5.48-6.07; P<1×10−15). Using MR, a one allele increase in smoking volume genetic risk score was associated with higher odds of COPD in ever smokers, (OR = 4.32; 95%CI:3.37-5.54; P<1×10−15), but no association was seen in IPF (OR=0.55; 95%CI: 0.17-1.81; P=0.33). No association was found between the genetic risk score and disease prevalence in never smokers with IPF (OR = 1.00; 95%CI:0.98-1.02; P=1.00) or COPD (OR = 1.00; 95%CI:0.99-1.01; P=0.53).Although both IPF and COPD are observationally associated with smoking, our analysis provides evidence inferring that the association is causal in COPD but there is no such evidence in IPF. This suggests that other environmental exposures also need consideration in IPF.
Shift work is associated with positive COVID-19 status in hospitalised patients
Authors: Maidstone Robert , Anderson Simon G , Ray David W , Rutter Martin K , Durrington Hannah J , Blaikley John F 
Published: December 2020

AbstractIntroductionShift work is associated with both mental, and physical ill health, including lung disease and infections. However, the impact of shift work on significant COVID-19 illness has not be assessed. We therefore investigated whether shift work is associated with COVID-19.Methods501,000 UK biobank participants were linked to secondary care SARS-CoV-2 PCR results from public health England. Healthcare workers and those without an occupational history were excluded from analysis.ResultsMultivariate logistic regression taking into account age, sex, ethnicity and deprivation index revealed that irregular shift work (OR 2.42 95%CI 1.92-3.05), permanent shift work (OR 2.5, 95%CI 1.95-3.19), day shift work (OR 2.01, 95%CI 1.55-2.6), irregular night shift work (OR 3.04, 95%CI 2.37-3.9) and permanent night shift work (OR 2.49, 95%CI 1.67-3.7) were all associated with positive COVID-19 tests compared to participants that did not perform shift work. This relationship persisted after adding sleep duration, chronotype, pre-morbid disease, BMI, alcohol and smoking. Work factors (proximity to a colleague combined with estimated disease exposure) were positively correlated with COVID-19 incidence (r2=0.248, p=0.02). If this was added to the model shift work frequency remained significantly associated with COVID-19. To control for non-measured occupational factors the incidence of COVID-19 in shift workers was compared to colleagues in the same job who did not do shift work. Shift workers had a higher incidence of COVID-19 (p<0.01).ConclusionsShift work is associated with a higher likelihood of in-hospital COVID-19 positivity. This risk could potentially be mitigated via additional workplace precautions or vaccination.
The Feasibility of Studying Metabolites in PICU Multi-Organ Dysfunction Syndrome Patients Over an 8-day Course Using An Untargeted Approach
Authors: Leimanis-Laurens Mara L. , Gil Danny , Kampfshulte Andrew , Krohn Claire , Prentice Elizabeth , Sanfilippo Dominic , Prokop Jeremy W. , Lydic Todd , Rajasekaran Surender 
Published: December 2020

AbstractMetabolites are generated from critical biological functions and metabolism. This pediatric study reviewed plasma metabolites in patients suffering from multi-organ dysfunction syndrome (MODS) in the pediatric intensive care unit (PICU) using an untargeted metabolomics approach. Patients meeting criteria for MODS were screened for eligibility and consented (n=24), and blood samples were collected at baseline, 72 hours, and 8 days; control patients (n=4), were presenting for routine sedation in an outpatient setting. A sub-set of MODS patients (n=8) required additional support with veno-atrial extracorporeal membrane oxygenation (VA-ECMO) therapy. Metabolites from thawed blood plasma were determined from ion pairing reversed-phase LC-MS analysis. Chromatographic peak alignment, identification, relative quantitation, statistical and bioinformatics evaluation were performed using MAVEN and MetaboAnalyst 4.0. Metabolite analysis revealed 115 peaks per sample. From the PLS-DA with VIP scores above ≥2.0, 7 dynamic metabolites emerged over the 3 time points: tauro-chenodeoxycholic acid (TCDCA), hexose,p-hydroxybenzoate, hydroxyphenylacetic acid (HPLA), 2_3-dihydroxybenzoic acid, 2-keto-isovalerate, and deoxyribose phosphate. After Bonferonni adjustment for repeated measures hexose andp-hydroxybenzoate were significant at one time point, or more. Kendall’s tau-b test was used for internal validation of creatinine. Metabolites may be benign or significant in describing a patient’s pathophysiology and require operator interpretation.
COVID-19 RELATED IMMUNIZATION DISRUPTIONS IN RAJASTHAN, INDIA: A RETROSPECTIVE OBSERVATIONAL STUDY
Authors: Jain Radhika , Chopra Ambika , Falézan Camille , Patel Mustufa , Dupas Pascaline 
Published: December 2020

ABSTRACTIntroductionGovernments around the world suspended immunization outreach to control COVID-19 spread. Many have since resumed services with an emphasis on catch-up vaccinations to reach children with missed vaccinations. This paper evaluated immunization disruptions during India’s March-May 2020 lockdown and the extent to which subsequent catch-up efforts reversed them in Rajasthan, India.MethodsIn this retrospective observational study, we conducted phone surveys to collect immunization details for 2,144 children that turned one year old between January and October 2020. We used logistic regressions to compare differences in immunization timeliness and completed first-year immunization status among children that were due immunizations just before (unexposed), during (heavily exposed), and after (post-exposure) the lockdown.ResultsRelative to unexposed children, heavily exposed children were significantly less likely to be immunized at or before 9 months (OR 0.550; 95%CI 0.367-0.824; p=0.004), but more likely to be immunized at 10-12 months (OR 1.761; 95%CI 1.196-2.591; p=0.004). They were also less likely to have completed their key first-year immunizations (OR 0.624; 95%CI 0.478-0.816; p=0.001) by the time of survey. In contrast, post-exposure children showed no difference in timeliness or completed first-year immunizations relative to unexposed children, and their immunization coverage was 6.9pp above heavily exposed children despite their younger age. Declines in immunization coverage were larger among children in households that were poorer, less educated, lower caste, and residing in COVID red zones, although subgroup comparisons were not statistically significant.ConclusionDisruptions to immunization services resulted in children missing immunization during the lockdown, but catch-up efforts after it was eased ensured many children were reached at later ages. Nevertheless, catch-up was incomplete and children due their immunizations during the lockdown remained less likely to be fully immunized 4-5 months after it lifted, even as younger cohorts due immunizations in June or later returned to pre-lockdown schedules.
PANOPLY: A cloud-based platform for automated and reproducible proteogenomic data analysis
Authors: Mani D. R. , Maynard Myranda , Kothadia Ramani , Krug Karsten , Christianson Karen E. , Heiman David , Clauser Karl R. , Birger Chet , Getz Gad , Carr Steven A. 
Published: December 2020

ABSTRACTProteogenomics involves the integrative analysis of genomic, transcriptomic, proteomic and post-translational modification data produced by next-generation sequencing and mass spectrometry-based proteomics. Several publications by the Clinical Proteomic Tumor Analysis Consortium (CPTAC) and others have highlighted the impact of proteogenomics in enabling deeper insight into the biology of cancer and identification of potential drug targets. In order to encapsulate the complex data processing required for proteogenomics, and provide a simple interface to deploy a range of algorithms developed for data analysis, we have developed PANOPLY—a cloud-based platform for automated and reproducible proteogenomic data analysis. A wide array of algorithms have been implemented, and we highlight the application of PANOPLY to the analysis of cancer proteogenomic data.
Cognitive and neural bases of decision-making causing civilian casualties during intergroup conflict
Authors: Han Xiaochun , Zhou Shuai , Fahoum Nardine , Wu Taoyu , Gao Tianyu , Shamay-Tsoory Simone , Gelfand Michele J. , Wu Xinhuai , Han Shihui 
Published: December 2020

AbstractCivilian casualties occur during military attacks. Such “collateral damage” is prohibited by international laws but increases with substantial consequences when intergroup conflict escalates. Here, we investigate cognitive and neural bases of decision-making processes resulting in civilian harm, using a task that simulates punishment decision-making during intergroup conflict. We test two groups of Chinese participants in a laboratory setting, and two ethnic groups (Jewish and Palestinian) in Israel. The results dissociate two psychological constructs, harm preference and harm avoidance, which respectively characterize punishment decision-making related to outgroup combatants and outgroup noncombatants during intergroup conflict. In particular, individuals show decreased avoidance of harming outgroup noncombatants when conflict escalates. Brain imaging (functional magnetic resonance imaging) reveals that decreased harm avoidance is predicted by inhibition of the left middle frontal activity during selection of punishment decisions. Our findings provide insight into the cognitive and neural bases of decision-making involving civilian harm during intergroup conflict.