bluuebunny/crossref_metadata_2025_split huggingface dataset:
Polygenic contribution for familial hypercholesterolemia (FH)
Authors: Medeiros Ana Margarida , Bourbon Mafalda 
Published: November 2021

Purpose of review
The present review summarizes different polygenic risk scores associated with hypercholesterolemia applied to cohorts with a genetic diagnosis of familial hypercholesterolemia (FH).

Recent findings
Several single-nucleotide polymorphisms associated with increased levels of LDL-C or Lp(a) have been genotyped in population cohorts with FH phenotype, to identify the cause of hypercholesterolemia in mutation negative individuals. In different studies, a large proportion of individuals without a monogenic causative variant (in low density lipoprotein receptor gene (LDLR), apolipoprotein B gene (APOB) or proprotein convertase subtilisin/kexin type 9 gene (PCSK9 genes) was considered to have a hypercholesterolemia with a polygenic basis. The heterogeneity in the phenotype of monogenic FH may also be explained by polygenic contributions to LDL-C. The elevated LDL-C genetic risk score (GRS) has been associated with increased risk of atherosclerotic cardiovascular disease in individuals with monogenic FH. Moreover, a poorer response to lipid lowering therapy has been associated with monogenic FH when compared to a polygenic basis. The reason why Lp(a) concentrations are raised in individuals with clinical FH is unclear, but it could be caused by a genetic variation in Lipoprotein(A) gene as a polygenic contribution.

Summary
Polygenic risk scores have revealed to be important tools to define the cause of hypercholesterolemia in FH mutation-negative individuals and should be included in FH diagnosis strategies, although there is still space for more specific LDL-C GRS to be developed. The use of GRS may be used to refine cardiovascular risk prediction in FH patients and could lead to a personalized approach to therapy. The identification of the genetic status of an individual with FH phenotype (monogenic or polygenic) may have implications on their risk stratification, cascade screening of relatives, disease management and therapeutic measures.
Disparities in Marijuana and Tobacco Smoke Incursions Among New York City Families During Early Months of the COVID-19 Pandemic
Authors: Zajac Lauren , Gallate Xanthe , Gu Gregory , Liu Bian , Elaiho Cordelia , Lin Elaine , Mogilner Leora , Oliver Kristin , Vangeepuram Nita , Wilson Karen 
Published: November 2021

Objectives:
Once the COVID-19 pandemic arrived in New York City (NYC), stay-at-home orders led to more time spent indoors, potentially increasing exposure to secondhand marijuana and tobacco smoke via incursions from common areas or neighbors. The objective of this study was to characterize housing-based disparities in marijuana and tobacco incursions in NYC housing during the pandemic.

Design:
We surveyed a random sample of families from May to July 2020 and collected sociodemographic data, housing characteristics, and the presence, frequency, and pandemic-related change in incursions.

Setting:
Five pediatric practices affiliated with a large NYC health care system.

Participants:
In total, 230 caregivers of children attending the practices.

Main Outcome Measures:
Prevalence and change in tobacco and marijuana smoke incursions.

Results:
Tobacco and marijuana smoke incursions were reported by 22.9% and 30.7%, respectively. Twenty-two percent of families received financial housing support (public housing, Section-8). Compared with families in private housing, families with financial housing support had 3.8 times the odds of tobacco incursions (95% CI, 1.4-10.1) and 3.7 times the odds of worsening incursions during pandemic (95% CI, 1.1-12.5). Families with financially supported housing had 6.9 times the odds of marijuana incursions (95% CI, 2.4-19.5) and 5 times the odds of worsening incursions during pandemic (95% CI, 1.9-12.8). Children in financially supported housing spent more time inside the home during pandemic (median 24 hours vs 21.6 hours, P = .02) and were more likely to have asthma (37% vs 12.9%, P = .001) than children in private housing.

Conclusions:
Incursions were higher among families with financially supported housing. Better enforcement of existing regulations (eg, Smoke-Free Public Housing Rule) and implementation of additional policies to limit secondhand tobacco and marijuana exposure in children are needed. Such actions should prioritize equitable access to cessation and mental health services and consider structural systems leading to poverty and health disparities.
Assessing Local Public Health Agency Alignment With Public Health 3.0: A Content Analysis of Illinois Community Health Improvement Plans
Authors: Welter Christina R. , Herrera Yadira , Uskali Amber L. , Seweryn Steve , Call Laurie , Lasky Samantha , Agbodo Nelson , Ezike Ngozi O. 
Published: November 2021

Context:
Public Health 3.0 described the need for public health agencies and the public health workforce to transform and obtain new skills and approaches to address the social determinants of health (SDOH) through cross-sectoral partnerships and collective action.

Objective:
To assess the current state of local health departments' Public Health 3.0 alignment through interventions and initiatives documented in community health improvement plans (CHIPs).

Method:
We conducted a content analysis of Illinois CHIPs from July to November 2020. A coding framework aligned with Public Health 3.0 concepts was developed on the basis of constructs from the literature, faculty expertise, and preliminary reviews of the CHIPs. Two researchers deductively coded for health priorities and interventions in Microsoft Excel 2016 and calculated the number of CHIPs in which each code appeared.

Results:
Ninety CHIPs representing 98 counties across the state were analyzed; 2 CHIPs were excluded because of a lack of strategies. Our content analysis found that 13% (n = 12) of CHIPs had explicit priorities related to SDOH and 12% (n = 11) included interventions that addressed socioeconomic factors. Ten percent (n = 9) of CHIPs proposed multilevel multicomponent interventions. Eighty-nine percent (n = 80) of CHIPs included community-level interventions, and 53% (n = 48) of CHIPs included policy, systems, and environmental strategies focused on specific health content. The majority of CHIPs (96%; n = 86) had at least 1 partnership strategy. Thirty-two percent (n = 29) of CHIPs mentioned the use of an evidence-based strategy.

Conclusions:
Our content analysis found opportunities to improve Illinois public health agencies' Public Health 3.0 capacities and capability. Findings are limited to this data source and definitions of the Public Health 3.0 attributes, leaving room for practice and research opportunities to develop operational definitions of Public Health 3.0; capacity building to improve the public health workforce readiness; and research and evaluation to measure improvements.
Reaching Consensus on Politicized Topics: A Convening of Public Health Professionals to Discuss Appropriate Abortion Activities for US Health Departments
Authors: Zaugg Claudia , Berglas Nancy F. , Johnson Regan , Roberts Sarah C. M. 
Published: November 2021

Context:
Public health professionals, particularly those in state and local health departments, do not always have clear understandings of their roles related to politically controversial public health topics. A process of consensus development among public health professionals that considers the best available evidence may be able to guide decision making and lay out an appropriate course of action.

Approach:
In May 2020, a group of maternal and child health and family planning professionals working in health departments, representatives of schools of public health, and members of affiliated organizations convened to explore values and principles relevant to health departments' engagement in abortion and delineate activities related to abortion that are appropriate for health departments. The convening followed a structured consensus process that included multiple rounds of input and opportunities for feedback and revisions.

Outcomes:
Convening participants came to consensus on principles to guide engagement in activities related to abortion, a set of activities related to abortion that are appropriate for health departments, and next steps to support implementation of such activities.

Lessons Learned:
The experience of the convening indicates that consensus processes can be feasible for politically controversial public health topics such as abortion.
The shifting age distribution of people with HIV using antiretroviral therapy in the United States
Authors: Althoff Keri N. , Stewart Cameron N. , Humes Elizabeth , Zhang Jinbing , Gerace Lucas , Boyd Cynthia M. , Wong Cherise , Justice Amy C. , Gebo Kelly A. , Thorne Jennifer E. , Rubtsova Anna A. , Horberg Michael A. , Silverberg Michael J. , Leng Sean X. , Rebeiro Peter F. , Moore Richard D. , Buchacz Kate , Kasaie Parastu 
Published: November 2021

Objective:
To project the future age distribution of people with HIV using antiretroviral therapy (ART) in the United States, under expected trends in HIV diagnosis and survival (baseline scenario) and achieving the ending the HIV epidemic (EHE) goals of a 75% reduction in HIV diagnoses from 2020 to 2025 and sustaining levels to 2030 (EHE75% scenario).

Design:
An agent-based simulation model with mathematical functions estimated from North American AIDS Cohort Collaboration on Research and Design data and parameters from the US Centers for Disease Control and Prevention's annual HIV surveillance reports.

Methods:
The PEARL (ProjEcting Age, MultimoRbidity, and PoLypharmacy in adults with HIV) model simulated individuals in 15 subgroups of sex-and-HIV acquisition risk and race/ethnicity. Simulation outcomes from the baseline scenario are compared with outcomes from the EHE75% scenario.

Results:
Under the baseline scenario, PEARL projects a substantial increase in number of ART-users over time, reaching a population of 909 638 [95% uncertainty range (UR): 878 449–946 513] by 2030. The overall median age increased from 50 years in 2020 to 52 years in 2030, with 23% of ART-users age ≥65 years in 2030. Under the EHE75% scenario, the projected number of ART-users was 718 348 [703 044–737 817] (median age = 56 years) in 2030, with a 70% relative reduction in ART-users <30 years and a 4% relative reduction in ART-users age ≥65 years compared to baseline, and persistent heterogeneities in projected numbers by sex-and-HIV acquisition risk group and race/ethnicity.

Conclusions:
It is critical to prepare healthcare systems to meet the impending demand of the US population aging with HIV.
Association Between State Limits on Opioid Prescribing and the Incidence of Persistent Postoperative Opioid Use Among Surgical Patients
Authors: Sun Eric C. , Rishel Chris A. , Waljee Jennifer F. , Brummett Chad M. , Jena Anupam B. 
Published: November 2021

Objective:
To examine whether laws limiting opioid prescribing have been associated with reductions in the incidence of persistent postoperative opioid use.

Summary of Background Data:
In an effort to address the opioid epidemic, 26 states (as of 2018) have passed laws limiting opioid prescribing for acute pain. However, it is unknown whether these laws have achieved their reduced the risk of persistent postoperative opioid use.

Methods:
We identified 957,639 privately insured patients undergoing one of 10 procedures between January 1, 2004 and September 30, 2018. We then estimated the association between persistent postoperative opioid use, defined as having filled ≥10 prescriptions or ≥120 days supply of opioids during postoperative days 91–365, and whether opioid prescribing limits were in effect on the day of surgery. States were classified as having: no limits, a limit of ≤7 days supply, or a limit of >7 days supply. The regression models adjusted for observable confounders such as patient comorbidities and also utilized a difference-in-differences approach, which relied on variation in state laws over time, to further minimize confounding.

Results:
The adjusted incidence of persistent postoperative opioid use was 3.5% (95%CI 3.3%-3.7%) for patients facing a limit of ≤7 days supply, compared with 3.3% (95%CI 3.3%-3.3%) for patients facing no prescribing limits (P = 0.13 for difference compared to no prescribing limits) and 3.4%, (95%CI 3.2%–3.6%) for patients facing a limit of >7 days supply (P = 0.43 for difference compared to no prescribing limits).

Conclusions:
Laws limiting opioid prescriptions were not associated with subsequent reductions in persistent postoperative opioid use.
Anti-membrane and anti-spike antibodies are long-lasting and together discriminate between past COVID-19 infection and vaccination
Authors: Amjadi Maya F. , Adyniec Ryan R. , Gupta Srishti , Bashar S. Janna , Mergaert Aisha M. , Braun Katarina M. , Moreno Gage K. , O’Connor David H. , Friedrich Thomas C. , Safdar Nasia , McCoy Sara S. , Shelef Miriam A. 
Published: November 2021

AbstractThe consequences of past COVID-19 infection for personal health and long-term population immunity are only starting to be revealed. Unfortunately, detecting past infection is currently a challenge, limiting clinical and research endeavors. Widely available anti-SARS-CoV-2 antibody tests cannot differentiate between past infection and vaccination given vaccine-induced anti-spike antibodies and the rapid loss of infection-induced anti-nucleocapsid antibodies. Anti-membrane antibodies develop after COVID-19, but their long-term persistence is unknown. Here, we demonstrate that anti-membrane IgG is a sensitive and specific marker of past COVID-19 infection and persists at least one year. We also confirm that anti-receptor binding domain (RBD) Ig is a long-lasting, sensitive, and specific marker of past infection and vaccination, while anti-nucleocapsid IgG lacks specificity and quickly declines after COVID-19. Thus, a combination of anti-membrane and anti-RBD antibodies can accurately differentiate between distant COVID-19 infection, vaccination, and naïve states to advance public health, individual healthcare, and research goals.
Identification of known and novel long non-coding RNAs potentially responsible for the effects of BMD GWAS loci
Authors: Abood Abdullah , Mesner Larry , Rosenow Will , Al-Barghouthi Basel M. , Horwitz Nina , Morgan Elise F. , Gerstenfeld Louis C. , Farber Charles R. 
Published: November 2021

AbstractOsteoporosis, characterized by low bone mineral density (BMD), is the most common complex disease affecting bone and constitutes a major societal health problem. Genome-wide association studies (GWASs) have identified over 1100 associations influencing BMD. It has been shown that perturbations to long non-coding RNAs (lncRNAs) influence BMD and the activities of bone cells; however, the extent to which lncRNAs are involved in the genetic regulation of BMD is unknown. Here, we combined the analysis of allelic imbalance (AI) in human acetabular bone fragments with a transcriptome-wide association study (TWAS) and expression quantitative trait loci (eQTL) colocalization analysis using data from the Genotype-Tissue Expression (GTEx) project to identify lncRNAs potentially responsible for GWAS associations. We identified 27 lncRNAs in bone that are located in proximity to a BMD GWAS association and harbor SNPs demonstrating AI. Using GTEx data we identified an additional 31 lncRNAs whose expression was associated (FDR correction<0.05) with BMD through TWAS and had a colocalizing eQTL (regional colocalization probability (RCP)>0.1). The 58 lncRNAs are located in 43 BMD associations. To further support a causal role for the identified lncRNAs, we show that 23 of the 58 lncRNAs are differentially expressed as a function of osteoblast differentiation. Our approach identifies lncRNAs that are potentially responsible for BMD GWAS associations and suggest that lncRNAs play a role in the genetics of osteoporosis.
Casirivimab and imdevimab for the treatment of hospitalized patients with COVID-19
Authors: Somersan-Karakaya Selin , Mylonakis Eleftherios , Menon Vidya P. , Wells Jason C. , Ali Shazia , Sivapalasingam Sumathi , Sun Yiping , Bhore Rafia , Mei Jingning , Miller Jutta , Cupelli Lisa , Hooper Andrea T. , Hamilton Jennifer D. , Pan Cynthia , Pham Viet , Zhao Yuming , Hosain Romana , Mahmood Adnan , Davis John D. , Turner Kenneth C. , Kim Yunji , Cook Amanda , Kowal Bari , Soo Yuhwen , DiCioccio A. Thomas , Geba Gregory P. , Stahl Neil , Lipsich Leah , Braunstein Ned , Herman Gary A. , Yancopoulos George D. , Weinreich David M. ,   COVID-19 Phase 2/3 Hospitalized Trial Team
Published: November 2021

AbstractBackgroundHospitalized patients with COVID-19 experience high mortality rates, ranging from 10% to 30%. Combined casirivimab and imdevimab (CAS+IMD) is authorized for use in outpatients with COVID-19 and in post-exposure prophylaxis. The UK-based platform RECOVERY study reported improved survival in hospitalized seronegative patients treated with CAS+IMD; however, in most of the world, anti-spike monoclonal antibody therapy is currently not approved for hospitalized patients.MethodsIn this phase I/II/III double-blind placebo-controlled trial, patients hospitalized with COVID-19 were randomized (1:1:1) to 2.4 g or 8.0 g of CAS+IMD or placebo, and characterized at baseline for viral load and SARS-CoV-2 endogenous immune response.Results1336 patients on low-flow or no supplemental oxygen were treated. The primary endpoint was met: in seronegative patients, the least squares mean difference (CAS+IMD vs placebo) for time-weighted average change from baseline viral load was –0.28 log10 copies/mL (95% confidence interval [CI] –0.51 to –0.05; P = .0172). The primary clinical analysis of death or mechanical ventilation from day 6 to 29 in patients with high viral load had a strong positive trend but did not reach significance. CAS+IMD numerically reduced all-cause mortality in seronegative patients through day 29 (relative risk reduction, 55.6%; 95% CI 24.2–74.0; nominal P = .0032). No safety concerns were noted.ConclusionsIn hospitalized patients with COVID-19 on low-flow or no oxygen, CAS+IMD treatment reduced viral load and the risk of death or mechanical ventilation as well as all-cause mortality in the overall population, with the benefit driven by seronegative patients and no harm observed in seropositive patients.
Prediction of the need for intensive oxygen supplementation during the hospitalization among patients with COVID 19 admitted to an academic health system in Texas, USA: a retrospective cohort study and development of a multivariable regression model
Authors: Davis John W. , Wang Beilin , Tomczak Ewa , Fu Chia-Chi , Harmouch Wissam , Reynoso David , Keiser Philip , Cabada Miguel M. 
Published: November 2021

ABSTRACTObjectiveThe severe acute respiratory syndrome-Coronavirus-2 (SARS-CoV-2) has caused a pandemic claiming more than 4 million lives worldwide. Overwhelming Coronavirus-Disease-2019 (COVID-19) respiratory failure placed tremendous demands on healthcare systems increasing the death toll. Cost-effective prognostic tools to characterize COVID-19 patients’ likely to progress to severe hypoxemic respiratory failure are still needed.DesignWe conducted a retrospective cohort study to develop a model utilizing demographic and clinical data collected in the first 12-hours admission to explore associations with severe hypoxemic respiratory failure in unvaccinated and hospitalized COVID-19 patients.SettingUniversity based healthcare system including 6 hospitals located in the Galveston, Brazoria and Harris counties of Texas.ParticipantsAdult patients diagnosed with COVID-19 and admitted to one of six hospitals between March 19thand June 31st, 2020.Primary outcomeThe primary outcome was defined as reaching a WHO ordinal scale between 6-9 at any time during admission, which corresponded to severe hypoxemic respiratory failure requiring high-flow oxygen supplementation or mechanical ventilation.ResultsWe included 329 participants in the model cohort and 62 (18.8%) met the primary outcome. Our multivariable regression model found that lactate dehydrogenase (OR 2.36), qSOFA score (OR: 2.26), and neutrophil to lymphocyte ratio (OR:1.15) were significant predictors of severe disease. The final model showed an area under curve (AUC) of 0.84. The sensitivity analysis and point of influence analysis did not reveal inconsistencies.ConclusionsOur study suggests that a combination of accessible demographic and clinical information collected on admission may predict the progression to severe COVID-19 among adult patients with mild and moderate disease. This model requires external validation prior to its use.STRENGTHS AND LIMITATIONS OF THIS STUDY⍰Our study utilized objective and measurable demographic and clinical information regularly available in healthcare settings even among patients unable to communicate.⍰Our primary outcome corresponds to WHO ordinal score which would allow compare our results to other studies and in other settings.⍰Our model could serve as an effective point of service tool during early admission to assist in clinical management and allocation of resources to unvaccinated patients.⍰Our study is a retrospective study of unvaccinated COVID19 patients, and validation of our prediction model in the rest of our study population is still needed.⍰In addition, testing our model in a more recent cohort after emergence of new SARS-CoV-2 variants will be needed to assess its robustness.
The learning curve of murine subretinal injection among clinically trained ophthalmic surgeons
Authors: Huang Peirong , Narendran Siddharth , Pereira Felipe , Fukuda Shinichi , Nagasaka Yosuke , Apicella Ivana , Yerramothu Praveen , Marion Kenneth M. , Cai Xiaoyu , Sadda Srinivas R. , Gelfand Bradley D. , Ambati Jayakrishna 
Published: November 2021

ABSTRACTPurposeSubretinal injection (SRI) in mice is widely used in retinal research, yet the learning curve (LC) of this surgically challenging technique is unknown.MethodsTo evaluate the LC for SRI in a murine model, we analyzed training data from 3 clinically trained ophthalmic surgeons from 2018 to 2020. Successful SRI was defined as either the absence of retinal pigment epithelium (RPE) degeneration after phosphate buffer saline injection and the presence of RPE degeneration afterAluRNA injection. Multivariable survival-time regression models were used to evaluate the association between surgeon experience and success rate, with adjustment for injection agents, and to calculate an approximate case number to achieve a 95% success rate. A Cumulative Sum (CUSUM) analysis was performed and plotted individually to monitor each surgeon’s simultaneous performance.ResultsDespite prior microsurgery experience, the combined average success rate of the first 50 cases in mice was only 27%. The predicted SRI success rate did not reach a plateau above 95% until approximately 364 prior cases. Using the 364-training case as a “cutoff” point, the predicted probability of success before and after the 364thcase was 65.38% and 99.32%, respectively (P< 0.0001). CUSUM analysis showed an initial upward slope and then remained within the decision intervals with an acceptable success rate set at 95% in the late stage.ConclusionsThis study demonstrates the complexity and substantial LC for successful SRI in mice with high confidence. A systematic training system could improve the reliability and reproducibility of SRI-related experiments and improve the interpretation of experimental results using this technique.Translational RelevanceOur prediction model and monitor system allow objective quantification of technical proficiency in the field of subretinal drug delivery and gene therapy for the first time.