bluuebunny/crossref_metadata_2025_split huggingface dataset:
Development and use of a method based on the anti-N reactivity of longitudinal samples to better estimate SARS-CoV-2 seroprevalence in a vaccinated population
Authors: Bazin Renée , Rochette Samuel , Perreault Josée , Fournier Marie-Josée , Grégoire Yves , Boivin Amélie , Lewin Antoine , Germain Marc , Renaud Christian 
Published: August 2022

ABSTRACTBackgroundEmerging evidence suggests that COVID-19 vaccination decreases the sensitivity of anti-nucleocapsid (N) serologies, making them less reliable to assess recently-acquired infections. We therefore developed and tested a new approach based on the ratio of the anti-N absorbance of longitudinal samples to overcome this limitation.MethodsPreviously vaccinated repeat plasma donors provided at least one pre-infection (reference) and one post-infection (test) sample. All samples were tested using an in-house anti-N ELISA. Seropositivity was determined based on the ratio between the anti-N absorbance of the test and reference samples. The ratio approach was tested in a real-world setting during three cross-sectional serosurveys carried out among plasma donors in Québec, Canada.ResultsUsing a cut-off ratio of 1.5, the approach had a sensitivity of 95.2% among the 248 previously vaccinated and infected donors compared with 63.3% for the conventional approach. When tested in a real-world setting, the ratio-based approach yielded an adjusted seroprevalence of 27.4% (95% confidence interval [CI]=23.8%-30.9%) at the latest time point considered, compared to 15.1% (95% CI=12.2%-18.0%) for the conventional approach.ConclusionsThis article describes a new and highly-sensitive approach that captures a significantly greater proportion of vaccinated individuals with a recent history of SARS-CoV-2 infection.
Extending Healthcare Access via Telemedicine in Public Libraries: A Mixed Methods Study
Authors: DeGuzman Pamela B. , Garth Jennifer , Sanjay Kamya , Compton Rebekah M. 
Published: August 2022

AbstractBackgroundDespite the potential for telemedicine in public libraries to expand healthcare access to those living a long distance from care and in broadband poor areas, there are few collaborations between libraries and healthcare providers offering these programs.PurposeTo explore licensed independent providers’ perspectives (LIPs) on telemedicine in public libraries as a method of improving equitable access to care for populations lacking the ability to connect to a telemedicine video visit from home.MethodsWe used a two-phase explanatory sequential mixed methods design with a quantitative strand followed by a qualitative strand to explore LIPs’ perspective on telemedicine in public libraries. Surveys were analyzed descriptively and to determine group differences. Survey respondents were recruited to participate in interviews, which were analyzed thematically using descriptive content analysis.FindingsFifty LIPs responded to the survey, and 12 were interviewed. Respondents were overwhelmingly supportive of telemedicine in public libraires, describing how video visits could help multiple vulnerable populations connect to providers when travel was cost prohibitive. They emphasized how connecting at-risk populations to a video visit instead of a telephone call allowed for a more thorough and accurate assessment. While several LIPs were concerned with privacy, others considered a library to be more private than the home. Interviews revealed how chronic illness management may be the ideal visit type for public library-based telemedicine.ConclusionsGiven the importance of expanding access sites for telemedicine, providers should consider partnering with libraries in their catchment areas where broadband access is sparse, and patients must travel long distances to care. Managing chronic illnesses using telemedicine in public libraries may be an important approach toward reducing health disparities in populations who live long distances from care and do not have home-based internet access.
Geographic barriers to care persist at the community healthcare level: evidence from rural Madagascar
Authors: Evans Michelle V , Andréambeloson Tanjona , Randriamihaja Mauricianot , Ihantamalala Felana , Cordier Laura , Cowley Giovanna , Finnegan Karen , Hanitriniaina Feno , Miller Ann C. , Ralantomalala Lanto Marovavy , Randriamahasoa Andry , Razafinjato Bénédicte , Razanahanitriniaina Emeline , Rakotonanahary Rado JL , Andriamiandra Isaïe Jules , Bonds Matthew H , Garchitorena Andres 
Published: August 2022

ABSTRACTGeographic distance is a critical barrier to healthcare access, particularly for rural communities with poor transportation infrastructure who rely on non-motorized transportation. There is broad consensus on the importance of community health workers (CHWs) to reduce the effects of geographic isolation on healthcare access. Due to a lack of fine-scale spatial data and individual patient records, little is known about the precise effects of CHWs on removing geographic barriers at this level of the healthcare system. Relying on a high-quality, crowd-sourced dataset that includes all paths and buildings in the area, we explored the impact of geographic distance from CHWs on the use of CHW services for children under 5 years in the rural district of Ifanadiana, southeastern Madagascar from 2018-2021. We then used this analysis to determine key features of an optimal geographic design of the CHW system, specifically optimizing a single CHW location or installing additional CHW sites. We found that consultation rates by CHWs decreased with increasing distance patients travel to the CHW by approximately 28.1% per km. The optimization exercise revealed that the majority of CHW sites (50/80) were already in an optimal location or shared an optimal location with a primary health clinic. Relocating the remaining CHW sites based on a geographic optimum was predicted to increase consultation rates by only 7.4%. On the other hand, adding a second CHW site was predicted to increase consultation rates by 31.5%, with a larger effect in more geographically dispersed catchments. Geographic distance remains a barrier at the level of the CHW, but optimizing CHW site location based on geography alone will not result in large gains in consultation rates. Rather, alternative strategies, such as the creation of additional CHW sites or proactive care, should be considered.
Potential utility of plasma p-tau and NfL as surrogate biomarkers for preventive clinical trials
Authors: Ferreira Pâmela C. L , Ferrari-Souza João Pedro , Tissot Cécile , Bellaver Bruna , Leffa Douglas T. , Lussier Firoza Z. , Povala Guilherme , Therriault Joseph , Benedet Andrea L. , Ashton Nicholas J. , Cohen Ann D. , Lopez Oscar L. , Tudorascu Dana L. , Klunk William E. , Soucy Jean-Paul , Gauthier Serge , Villemagne Victor L. , Zetterberg Henrik , Blennow Kaj , Rosa-Neto Pedro , Zimmer Eduardo R , Karikari Thomas K. , Pascoal Tharick A. ,   Alzheimer’s Disease Neuroimaging Initiative
Published: August 2022

AbstractBackgroundAlthough longitudinal changes in plasma phosphorylated tau 181 (p-tau181) and neurofilament light (NfL) correlate with Alzheimer’s disease (AD) progression, it is unknown whether these changes can be used to monitor drug effects in preventive clinical trials. Here, we tested the utility of changes in plasma p-tau181 and NfL as surrogate biomarkers for clinical trials focusing on cognitively unimpaired (CU) individuals.MethodsWe evaluated 257 CU older individuals with amyloid-beta (Aβ) positron emission tomography (PET) at baseline, as well as the baseline, up to 24-month plasma p-tau181 and NfL measures. Linear regressions and Cox-proportional hazards tested the associations of change in markers with age and clinical progression, respectively. We estimated the sample size needed to test a 25% drug effect with 80% of power at a 0.05 level on reducing changes in plasma markers.ResultsLongitudinal changes in plasma NfL were associated with age, while changes in plasma p-tau181 with progression to amnestic MCI. Clinical trial using p-tau181 and NfL would require 78% and 63% smaller sample sizes, respectively, for a 24-month than a 12-month follow-up. The use of Aβ positivity for enrichment had a larger impact on reducing the sample size required for trials using p-tau181 (43% reduction) than NfL (17%) as surrogate. Notably, population enrichment with intermediate levels of Aβ, rather than merely Aβ positivity, reduced the sample size by 88% for p-tau181 and 64% for NfL over 12 months, and by 73% for p-tau181 and 59% for NfL over 24 months.ConclusionOur results highlighted that changes in plasma NfL could be used as a surrogate for age-related degeneration, while longitudinal changes in plasma p-tau181 were associated with parallel clinical progression. A follow-up duration of 24 months was associated with more stable changes in plasma measures and, consequently, a greater effect size than a follow-up period of 12 months. The enrollment of CU subjects with intermediate levels of Aβ constitutes the alternative with the largest effect size for clinical trials quantifying plasma p-tau181 and NfL over 12 and 24 months.
Alignment of Community Benefit Spending and Initiatives to Improve Community Health: Is There Evidence of Progress?
Authors: Sapirstein Abel , Rao Arthi , Steimle Lauren N. 
Published: August 2022

AbstractObjectivesWe sought to identify changes in non-profit hospitals’ community benefit spending from 2014 to 2019. Secondly, we wanted to find novel predictors of spending in the most recent available data.MethodsFor our longitudinal analysis, we used tax filing data for 1072 hospitals from 2014-2019 and time-based ANOVA. We gathered information about hospital characteristics, the social determinants of health, and hospital partnerships with local communities for 1192 hospitals for the year 2019. We employed multivariate regression to identify significant factors.ResultsTotal community benefit spending rose from 8.1% in 2014 to 9.1% of operating expenses in 2019, driven by increased spending on patient care. There was no such increase in spending on activities targeted at improving community health. The presence and strength of partnerships between hospitals and their communities were associated with higher community benefit spending.ConclusionsWe found no evidence of dramatic shifts in community benefit spending from 2014 to 2019. Further, we identified partnerships for population health improvement as an effective, novel predictor of community benefit spending. Supporting partnerships between hospitals and communities may help facilitate strategic investments in community health improvement.
Effects of Long-Term Supplementation of Eggs on Growth, Biochemical Indices, and Microbiota of Rural Thai Primary School Children
Authors: Suta Sophida , Surawit Apinya , Mongkolsucharitkul Pichanun , Pinsawas Bonggochpass , Manosan Thamonwan , Ophakas Suphawan , Pongkunakorn Tanyaporn , Pumeiam Sureeporn , Sranacharoenpong Kitti , Sutheeworapong Sawannee , Phuangsombut Patcha , Khoomrung Sakda , Thaipisuttikul Iyarit , Mayurasakorn Korapat 
Published: August 2022

SummaryBackgroundProtein-energy malnutrition is still problematic worldwide. It directly impacts growth and development, especially in children. We investigated the long-term effects of egg supplementation on the growth, biochemical indices, and microbiota of primary school children.MethodsA randomized controlled cluster study was carried out in six rural schools in Thailand. Participants were randomly assigned into three groups: 1) whole egg (WE) – consuming 10 additional eggs/week [n = 238], 2) protein substitute (PS) - consuming yolk-free egg substitute equivalent to 10 eggs/week [n = 200], and 3) control group (n= 197]). Demographic and biochemical indices, and microbiota composition were measured at weeks 0, 14, and 35.Findings635 students (8 to 14 years old) were recruited (51·5% female). At baseline, 17% of the participants were underweight, 18% were stunted, and 13% were wasted. At week 35, compared to the control group, body weight and height increased significantly in WE (3·6 ± 23·5 kg,P<0·001 and 5·1 ± 23·2 cm,P<0·001). No significant differences in weight or height were observed between PS and Control. Prealbumin levels were higher (1·5 ± 8·158·6314 mg/dL,P<0·001) in WE, but not in PS, compared to control. Significant decreases in total cholesterol, triglycerides, and LDL cholesterol were observed in the WE, but not in the PS groups. HDL cholesterol tended to increase in WE (0·7 ± 25·2 mg/dL,ns). Neither the alpha nor beta diversity of the bacterial diversity was significantly different among all groups. After WE supplementation, the overall relative abundance ofBifidobacteriumincreased by 1·28-fold as compared to baseline and the differential abundance analysis also indicated thatLachnospiraincreased significantly andVaribaculumdecreased.InterpretationLong-term whole egg supplementation is an effective, feasible and low-cost intervention to reduce protein-energy malnutrition, particularly in low-middle-income countries. Whole egg supplementation improves growth and nutritional biomarkers, and positively impacts gut microbiota without adverse effects on blood cholesterol levels.FundingAgricultural Research Development Agency (ARDA) of Thailand (PRP6105022310, PRP6505030460).
Field assessment of BinaxNOW antigen tests as COVID-19 treatment entry point at a community testing site in San Francisco during evolving omicron surges
Authors: Schrom John , Marquez Carina , Wang Chung-Yu , Saxena Aditi , Mitchell Anthea M. , Ribeiro Salu , Pilarowski Genay , Nakamura Robert , Rojas Susana , Black Douglas , Contreras Oseguera Maria G. , Diaz Edgar Castellanos , Payan Joselin , Rojas Susy , Jones Diane , Tulier-Laiwa Valerie , Zavaleta Aleks , Martinez Jacqueline , Chamie Gabriel , Glaser Carol , Jacobsen Kathy , Petersen Maya , DeRisi Joseph , Havlir Diane 
Published: August 2022

ABSTRACTBackgroundCOVID-19 oral treatments require initiation within 5 days of symptom onset. Although antigen tests are less sensitive than RT-PCR, rapid results could facilitate entry to treatment. As SARS-CoV-2 variants and host immunity evolve, it is important to characterize the use case for rapid antigen tests for treatment entry.MethodsWe collected anterior nasal swabs for BinaxNOW and RT-PCR testing and clinical data at a walk-up, community site in San Francisco, California between January and June 2022. SARS-CoV-2 genomic sequences were generated from positive samples and classified according to subtype and variant. Monte Carlo simulations were conducted to estimate the expected proportion of SARS-CoV-2 infected persons who would have been diagnosed within 5 days of symptom onset using RT-PCR versus BinaxNOW testing.ResultsAmong 25,309 persons tested with BinaxNOW, 2,952 had concomitant RT-PCR. 1321/2952 (44.7%) were SARS-CoV-2 RT-PCR positive. We identified waves of predominant omicron BA.1, BA.2, BA.2.12, BA.4, and BA.5 among 720 sequenced samples. Among 1,321 RT-PCR positive samples, 938/1321 (71%) were detected by BinaxNOW; 95% (774/817) of those with Ct value <30 were detected by BinaxNOW. BinaxNOW detection was consistent over lineages. In analyses to evaluate entry to treatment, BinaxNOW detected 82.7% (410/496, 95% CI: 79-86%) of persons with COVID-19 within 5 days of symptom onset. In comparison, RT-PCR (24-hour turnaround) detected 83.1% (412/496 95% CI: 79-86%) and RT-PCR (48-hour turnaround) detected 66.3% (329/496 95% CI: 62-70%) of persons with COVID-19 within 5 days of symptom onset.ConclusionsBinaxNOW detected high viral load from anterior nasal swabs consistently across omicron sublineages emerging between January and June of 2022. Simulations support BinaxNOW as an entry point for COVID-19 treatment in a community field setting.
Prevalence and Characterization of Bacteria Present in the Nasopharynx of Outpatients with and without SARS-CoV-2
Authors: Shurko James F. , Mares Chris A. , Page Robert B. , Lopez Kristina , Nguyen Vivian , Vanee Niti , Mishra Pramod K. 
Published: August 2022

AbstractCOVID-19 has emerged as a highly contagious and debilitating disease caused by the SARS-CoV-2 virus and has claimed the lives of over 6.8 million people worldwide. Bacterial co-infections are one of many co-morbidities that have been suggested to impact the outcome of COVID-19 in patients. The primary goal of this study was to assess the prevalence of bacterial co-infections and to describe any trends observed during the height of the COVID-19 pandemic. To do this, we investigated SARS-CoV-2 and bacterial co-infections from outpatient RT-PCR testing in Texas. The results indicateStaphylococcus aureus, Streptococcus pneumoniae, Klebsiella pneumoniae, Moraxella catarrhalis, andHaemophilus influenzaewere the most frequently detected bacterial pathogens in both SARS-CoV-2 positive and SARS-CoV-2 negative patients and that these bacterial pathogens were present in these two patient populations at similar proportions. We also detectedStaphylococcus aureusin a significantly larger proportion of males relative to females and people under 65 years of age relative to those 65 and over. Finally, we found that Hispanics were 75% more likely to be SARS-CoV-2 positive than non-Hispanics. The results suggest that COVID-19 patients may benefit from rapid diagnostic tests for bacterial pathogens and that this information could help delineate targeted antimicrobial therapy.
PHFinder: Assisted detection of point heteroplasmy in Sanger sequencing chromatograms
Authors: Suarez-Menendez Marcos , Rivera-Leon Vania , Robbins Jooke , Bérubé Martine , Palsbøll Per J. 
Published: August 2022

AbstractHeteroplasmy is the presence of two or more organellar genomes (mitochondrial or plastid DNA) in an organism, tissue, cell or organelle. Heteroplasmy can be detected by visual inspection of Sanger sequencing chromatograms, where it appears as multiple peaks of fluorescence at a single nucleotide position. Visual inspection of chromatograms is both consuming and highly subjective, as heteroplasmy is difficult to differentiate from background noise. Few software solutions are available to automate the detection of point heteroplasmies, and those that are available are typically proprietary, lack customization or are unsuitable for automated heteroplasmy assessment in large datasets.Here, we present PHFinder, a Python-based, open source tool to assist in the detection of point heteroplasmies in large numbers of Sanger chromatograms. PHFinder automatically identifies point heteroplasmies directly from the chromatogram trace data. The program was tested with Sanger sequencing data from 100 humpback whale (Megaptera novaeangliae) tissue samples with known heteroplasmies.PHFinder detected most (90%) of the known heteroplasmies thereby greatly reducing the amount of visual inspection required. PHFinder is flexible, enabling explicit specification of key parameters to infer double peaks (i.e., heteroplasmies).
Neuronal, Affective, and Sensory Correlates of Targeted Helping Behavior in Male and Female Sprague Dawley Rats
Authors: Cox Stewart S. , Brown Brogan J. , Woods Samuel K , Brown Samantha J. , Kearns Angela M. , Reichel Carmela M. 
Published: August 2022

AbstractEmpathy is an innate ability to understand the emotional states of others along with the motivation to improve it. It has evolved over time into highly complex behaviors, the basis of which can be described using the Perception Action Model (PAM), where shared affect promotes an action that eliminates the distress of both the passive “Target” and, by extension, the active “Observer.” There are myriad biological variables that may modulate empathic behavior, including sex, sensory modalities, and neural activity. In the following studies, using our lab’s model of social contact-independent targeted helping, we first tested whether sex differences exist in helping behavior. Next, we explored sex differences in sensory and affective signaling, including the impact of direct visualization of a distressed conspecific and the type of ultrasonic vocalizations (USV) made between animal pairs during the task. Finally, we examined the neural activity of multiple cortical and subcortical regions of interest across time during targeted helping between males and females. We show both sexes exhibit similar helping behavior, but sensory and affective signaling differs between sexes. Further, changes in neural activity exhibited distinct sex-specific patterns across time. Our results indicate sex differences are not a ubiquitous presence in targeted helping. Instead, it is likely sex differences may be a convergent phenomenon in which the behavior is similar, but the underlying biological mechanisms are distinct. These results lay the groundwork for future studies to explore the similarities and differences that drive empathic behavior in both males and females.
Mapping the landscape of genetic dependencies in chordoma
Authors: Sharifnia Tanaz , Wawer Mathias J. , Goodale Amy , Lee Yenarae , Kazachkova Mariya , Dempster Joshua M. , Muller Sandrine , Levy Joan , Freed Daniel M. , Sommer Josh , Kalfon Jérémie , Vazquez Francisca , Hahn William C. , Root David E. , Clemons Paul A. , Schreiber Stuart L. 
Published: August 2022

ABSTRACTIdentifying the spectrum of genes required for cancer cell survival can reveal essential cancer circuitry and therapeutic targets, but such a map remains incomplete for many cancer types. We applied genome-scale CRISPR-Cas9 loss-of-function screens to map the landscape of selectively essential genes in chordoma, a bone cancer with few validated targets. This approach confirmed a known chordoma dependency, TBXT (T; brachyury), and identified a range of additional dependencies, including PTPN11, ADAR, PRKRA, LUC7L2, SRRM2, SLC2A1, SLC7A5, FANCM, and THAP1. CDK6, SOX9, and EGFR, genes previously implicated in chordoma biology, were also recovered. We found genomic and transcriptomic features that predict specific dependencies, including interferon-stimulated gene expression, which correlates with ADAR dependence and is elevated in chordoma. Validating the therapeutic relevance of dependencies, small-molecule inhibitors of SHP2, encoded by PTPN11, had potent preclinical efficacy against chordoma. Our results generate an emerging map of chordoma dependencies to enable biological and therapeutic hypotheses.
Does oxidative stress shorten telomeres in vivo? A meta-analysis
Authors: Armstrong Emma , Boonekamp Jelle 
Published: August 2022

AbstractTelomere attrition is considered a hallmark of ageing. Untangling the proximate causes of telomere attrition may therefore reveal important aspects about the ageing process. In a landmark paper in 2002 Thomas von Zglinicki demonstrated that oxidative stress causes telomere attrition in cell culture. In the next 20 years, oxidative stress became firmly embedded into modern theories of ageing and telomere attrition. However, a recent surge of in vivo studies reveals an inconsistent pattern questioning the unequivocal role of oxidative stress in telomere dynamics, in living organisms. Here we report the results of the first formal meta-analysis on the association between oxidative stress and telomere dynamics in vivo, representing 37 studies, 4,834 individuals, and 18,590 correlational measurements. The overall correlation between oxidative stress markers and telomere dynamics was indistinguishable from zero. This result was independent of the type of oxidative stress marker, telomere dynamic, or taxonomic group. However, telomere measurement method affected the analysis with TRF but not qPCR-based studies showing a significant overall correlation. The correlation was more pronounced in short-lived species and during the adult life phase, when ageing becomes apparent. We then performed an additional meta-analysis of interventional studies (n=7) manipulating oxidative stress. This revealed a significant effect of treatment on telomere dynamics. Our findings indicate that oxidative stress may have a profound effect on telomere dynamics in living organisms fundamentally underpinning the process of ageing.