Tag: pubmed

PLoS Genet. 2021 Jun 1;17(6):e1009596. doi: 10.1371/journal.pgen.1009596. Online ahead of print.

ABSTRACT

The rapid decrease in sequencing cost has enabled genetic studies to discover rare variants associated with complex diseases and traits. Once this association is identified, the next step is to understand the genetic mechanism of rare variants on how the variants influence diseases. Similar to the hypothesis of common variants, rare variants may affect diseases by regulating gene expression, and recently, several studies have identified the effects of rare variants on gene expression using heritability and expression outlier analyses. However, identifying individual genes whose expression is regulated by rare variants has been challenging due to the relatively small sample size of expression quantitative trait loci studies and statistical approaches not optimized to detect the effects of rare variants. In this study, we analyze whole-genome sequencing and RNA-seq data of 681 European individuals collected for the Genotype-Tissue Expression (GTEx) project (v8) to identify individual genes in 49 human tissues whose expression is regulated by rare variants. To improve statistical power, we develop an approach based on a likelihood ratio test that combines effects of multiple rare variants in a nonlinear manner and has higher power than previous approaches. Using GTEx data, we identify many genes regulated by rare variants, and some of them are only regulated by rare variants and not by common variants. We also find that genes regulated by rare variants are enriched for expression outliers and disease-causing genes. These results suggest the regulatory effects of rare variants, which would be important in interpreting associations of rare variants with complex traits.

PMID:34061836 | DOI:10.1371/journal.pgen.1009596

PLoS Comput Biol. 2021 Jun 1;17(6):e1008927. doi: 10.1371/journal.pcbi.1008927. Online ahead of print.

ABSTRACT

Information processing can leave distinct footprints on the statistics of neural spiking. For example, efficient coding minimizes the statistical dependencies on the spiking history, while temporal integration of information may require the maintenance of information over different timescales. To investigate these footprints, we developed a novel approach to quantify history dependence within the spiking of a single neuron, using the mutual information between the entire past and current spiking. This measure captures how much past information is necessary to predict current spiking. In contrast, classical time-lagged measures of temporal dependence like the autocorrelation capture how long-potentially redundant-past information can still be read out. Strikingly, we find for model neurons that our method disentangles the strength and timescale of history dependence, whereas the two are mixed in classical approaches. When applying the method to experimental data, which are necessarily of limited size, a reliable estimation of mutual information is only possible for a coarse temporal binning of past spiking, a so-called past embedding. To still account for the vastly different spiking statistics and potentially long history dependence of living neurons, we developed an embedding-optimization approach that does not only vary the number and size, but also an exponential stretching of past bins. For extra-cellular spike recordings, we found that the strength and timescale of history dependence indeed can vary independently across experimental preparations. While hippocampus indicated strong and long history dependence, in visual cortex it was weak and short, while in vitro the history dependence was strong but short. This work enables an information-theoretic characterization of history dependence in recorded spike trains, which captures a footprint of information processing that is beyond time-lagged measures of temporal dependence. To facilitate the application of the method, we provide practical guidelines and a toolbox.

PMID:34061837 | DOI:10.1371/journal.pcbi.1008927

J Am Acad Orthop Surg. 2021 May 31. doi: 10.5435/JAAOS-D-20-01352. Online ahead of print.

ABSTRACT

INTRODUCTION: Based on preoperative and perioperative risk factors that have been found to correlate with the development of acute kidney injury (AKI), our institution developed a protocol aimed at managing and improving outcomes in all elective THA and TKA patients. This article highlights the continued success and growth of our protocol aimed at decreasing AKI and hypotension in elective total joint arthroplasty patients.

METHOD: A multidisciplinary team comprising orthopaedic surgeons, nephrologists, anesthesiologists, cardiologists, and internal medicine hospitalists created a comprehensive protocol aimed at decreasing complications after elective joint arthroplasty and improving clinical outcomes across multiple hospitals. Patient demographics, hospital length of stay, readmission rates, mortality, and postoperative AKI and hypotension incidences were recorded and compared between preprotocol phase I (initial protocol implementation) and phase II (protocol expansion across 10 hospitals) patient cohorts.

RESULTS: Overall, 3,222 patients over 56 months and 10 hospitals were included. Our phase II AKI rate (0.6%) was significantly lower than our preprotocol rate (6.2%, P < 0.01) and statistically similar to our phase I rate (1.2%, P = 0.61). Our hypotension rate in phase II (6.8%) was significantly lower than our preprotocol rate (12.7%, P < 0.01) but statistically similar to our phase I rate (5.9%, P = 0.40). Furthermore, a significant decrease was observed in hospital length of stay (P < 0.01) over time, but no difference was observed in readmission (P = 0.59) and mortality rates (P = 1.00) over time.

DISCUSSION: This protocol-driven interventional study provides a detailed and successful multidisciplinary method to manage and decrease rates of AKI and hypotension in a large patient cohort across multiple hospital centers.

PMID:34061804 | DOI:10.5435/JAAOS-D-20-01352

JMIR Public Health Surveill. 2021 May 29. doi: 10.2196/23876. Online ahead of print.

ABSTRACT

BACKGROUND: Background: There is still an HIV epidemic in the U.S., which is a substantial issue for priority populations bearing a disproportionate burden of HIV infection. Daily oral pre-exposure prophylaxis (PrEP) has been shown to be safe and effective in reducing sexual HIV acquisition risk. However, studies document that PrEP awareness/usage is low. There is also a limited understanding of social media, such as Instagram, as a PrEP information source.

OBJECTIVE: Given the paucity of research on PrEP-related Instagram posts and popularity of the social media platform, the purpose of this research is to describe the source characteristics, image type, and textual content of PrEP-related posts on Instagram.

METHODS: Using Crowdtangle Search, a public insights tool owned/operated by Facebook, we retrieved publicly accessible and English-language-only Instagram posts for the 12-month period preceding April 22, 2020, using the terms: Truvada or “pre-exposure prophylaxis” or #truvada or #truvadaprep or #truvadawhore or #truvadaforprep. We employed a qualitative coding methodology to manually extract information from posts. Using a pre-tested codebook, we performed a content analysis on N=250 posts, examining message and source characteristics (i.e., organization type [e.g., government, news], individual type [e.g., doctor]), including specific information about PrEP (e.g., how it works, its cost) and indicated users. Frequencies and percentages were calculated for all categorical variables. A chi-square analysis was conducted to determine differences between source types on a variety of message characteristics.

RESULTS: Three-quarters of posts (n=193, 77.2%) were posted by organizations. Of the 250 posts reviewed, about two-thirds (n=174, 69.6%) included a photograph, more than half (n=142, 56.8%) included an infographic, and one in 10 (n=30, 12%) included a video. More than half defined PrEP (n=137, 54.8%), but fewer posts promoted PrEP use, explained how PrEP works, and included information on effectiveness or who can use PrEP. The most commonly hashtagged population among posts was men who have sex with men, but not necessarily bisexual men. Few posts contained race/ethnicity-related hashtags (n=11, 4.4%). Fewer posts contained transgender-associated tags (e.g., #transgirl; n=5, 2.0%). No posts contained tags related to heterosexuals or injection drug users. We found statistical differences between source types (i.e., individual versus organization). Specifically, posts from organizations more frequently contained information about who can use PrEP, whereas posts from individuals more frequently contained information describing side effects.

CONCLUSIONS: This study is among the first to review Instagram for content related to PrEP, and it answers the National AIDS Strategy’s call to more clearly articulate the science surrounding HIV risk/prevention through a better understanding of the current public information environment. This study offers a snapshot of how PrEP is being discussed (and by whom) on one of the most popular social media platforms and provides a foundation for developing and implementing PrEP promotion interventions on Instagram.

PMID:34061759 | DOI:10.2196/23876

Infez Med. 2021 Jun 1;29(2):167-180.

ABSTRACT

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome virus 2 (SARS-CoV-2), in a very short span of thirteen months has taken a considerable toll on humanity, resulting in over 3 million deaths with more than 150 million confirmed cases as on May 1, 2021. In the scarcity of a potential antiviral and protective vaccine, COVID-19 has posed high public health concerns, panic, and challenges to limit the spread of this pandemic virus. Only recently have a few vaccine candidates been developed, and vaccination programs have started in some countries. Multiple clinical presentations of COVID-19, animal spillover, cross-species jumping, zoonotic concerns, and emergence of virus variants have altogether created havoc during this ongoing pandemic. Several bodies of research are continuously working to elucidate the exact molecular mechanisms of the pathogenesis. To develop a prospective antiviral therapy/vaccine for SARSCoV-2, it is quite essential to gain insight into the immunobiology and molecular virology of SARS-CoV-2. A thorough literature search was conducted up to 28th February 2021 in the PubMed and other databases for the articles describing the immunopathology and immune response of SARS-CoV-2 infection, which were critically evaluated and used to compile this article to present an overall update. Some of the information was drawn from studies on previous MERS and SARS viruses. Innate as well as adaptive immunity responses are elicited by exposure to SARS-CoV-2. SARS-CoV-2 establishes a successful infection by escaping the host immunity as well as over activating the innate immune mechanisms that result in severe disease outcomes, including cytokine storm. This review summarizes the immunopathology and molecular immune mechanisms elicited during SARS-CoV-2 infection, and their similarities with MERS-CoV and SARS-CoV.

PMID:34061781

Infez Med. 2021 Jun 1;29(2):229-235.

ABSTRACT

Interferon-γ releasing assays (IGRAs) are currently widely employed in the initial work up of Mycobacterium tuberculosis infection, as well as in suspected tuberculosis (TB). These assays are commonly utilized over the Tuberculin Skin Test (TST) in high resource and low TB burden settings, despite the unclear benefits shown in such contexts. The debate on the use of TST and IGRAs is of current interest also in Italy due to the increasing presence of immigrants from countries with a high incidence of TB and the rising attention of health care institutions to economic costs. The aim of this study was to compare QuantiFERON-TB (QFT) and TST results in active TB. We evaluated QFT results and TST reactions from 245 consecutive patients having both tests, registered among 411 patients admitted for TB at the Infectious Disease Clinic, Department of Medicine of the University of Perugia (Italy). We compared the rates of positive QFT and TST tests and noted no statistically significant differences overall or in relation to age, gender, HIV status and TB localization. Among foreign-born patients with confirmed TB, we observed a lower rate of positive TST results. The results of our study indicated that both QFT and TST can be used in the work up of TB having special attention when evaluating foreign-born patients.

PMID:34061788

Multivariate Behav Res. 2021 Jun 1:1-20. doi: 10.1080/00273171.2021.1919048. Online ahead of print.

ABSTRACT

The information matrix or its inverse variance-covariance matrix for the maximum likelihood estimates of model parameters in diagnostic classification models plays a key role in statistical inference. Although both the item and structural parameters should be contained in the calculation of the information matrix simultaneously, previous studies have mainly focused on performance of the item parameter standard error (SE), no study has investigated the structural parameter SE estimation methods systematically. In this study, we propose a class of structural parameter SE estimation methods based on the empirical cross-product matrix, the observed information matrix, and the sandwich-type covariance matrix. A simulation study was conducted under different attribute hierarchy structures, the findings suggest that the proposed methods are useful for empirical researchers and practitioners in evaluating the variability of structural parameter estimators. We illustrate the application of the structural parameter SE estimation methods for exploring the presence of an attribute hierarchy using real data.

PMID:34061682 | DOI:10.1080/00273171.2021.1919048

Health Commun. 2021 Jun 1:1-10. doi: 10.1080/10410236.2021.1932109. Online ahead of print.

ABSTRACT

Given the politicization of abortion, professionals working in U.S. health departments (HDs) may not be receptive to communications about abortion, despite often regulating abortion facilities. This paper reports results of a randomized, prospective, observational study to test the effects of e-mail language when disseminating evidence on abortion to HD professionals. Our sample was 302 HD employees who oversee healthcare facilities inspection/regulation in all 50 U.S. state HDs, clustered by HD and randomized into two study groups. In November-December 2019, we sent biweekly e-mails containing links to a website summarizing evidence on abortion facility regulation. E-mails/headers sent to one group emphasized public health values and did not include the word abortion; e-mails/headers to the other group used the word abortion. Primary outcome measures were e-mail open rates and click-through rates. Among 221 participants to whom e-mails were deliverable, the overall open rate was 36%. Open rate was 25% for PH values and 46% for abortion groups (p < .05). Effects were moderated by state abortion policy environment: in both supportive and restrictive environments, participants in the abortion messaging group were statistically more likely to open e-mails than those in the PH values group. There was no difference between groups in states with middle-ground abortion policy environments. Among participants opening at least one e-mail, 19% clicked through to the website, with no significant difference by group. This study demonstrates that repeated targeted e-mail campaigns can reach HD professionals with research summaries. Concerns that communications to HDs should avoid the word abortion are unsupported.

PMID:34061693 | DOI:10.1080/10410236.2021.1932109

Cranio. 2021 Jun 1:1-9. doi: 10.1080/08869634.2021.1933307. Online ahead of print.

ABSTRACT

OBJECTIVE: To investigate the link between malocclusions and temporomandibular disorders (TMD) with a focus on iatrogenic malocclusion. Other etiologies of TMD (oral parafunctions) were also assessed.

METHODS: The prevalence of malocclusions was correlated in two groups: patients with TMD (case group) and patients without TMD (control group). Malocclusions involving dental care were specified. Parafunctions in the case group were assessed.

RESULTS: A statistically significant association between TMD and overbite >4 mm, interferences in laterotrusion, and absence of Angle Class I was shown. A potential deleterious effect of iatrogenic malocclusions was highlighted.

CONCLUSION: The multifactorial etiology of TMD was confirmed because an association between TMD and three malocclusions was found, and all case patients had parafunction(s). Current recommendations advising first a reversible treatment, TMD care should start with a behavioral re-education to remove parafunctions. However, it is essential to avoid creating iatrogenic malocclusion during dental care.

PMID:34061714 | DOI:10.1080/08869634.2021.1933307

Am Soc Clin Oncol Educ Book. 2021 Jun;41:e133-e144. doi: 10.1200/EDBK_319783.

ABSTRACT

Misgivings have been raised about the operating characteristics of the canonical 3+3 dose-escalation phase I clinical trial design. Yet, the traditional 3+3 design is still the most commonly used. Although it has been implied that adhering to this design is due to a stubborn reluctance to adopt change despite other designs performing better in hypothetical computer-generated simulation models, the continued adherence to 3+3 dose-escalation phase I strategies is more likely because these designs perform the best in the real world, pinpointing the correct dose and important side effects with an acceptable degree of precision. Beyond statistical simulations, there are little data to refute the supposed shortcomings ascribed to the 3+3 method. Even so, to address the unique nuances of gene- and immune-targeted compounds, a variety of inventive phase 1 trial designs have been suggested. Strategies for developing these therapies have launched first-in-human studies devised to acquire a breadth of patient data that far exceed the size of a typical phase I design and blur the distinction between dose selection and efficacy evaluation. Recent phase I trials of promising cancer therapies assessed objective tumor response and durability at various doses and schedules as well as incorporated multiple expansion cohorts spanning a variety of histology or biomarker-defined tumor subtypes, sometimes resulting in U.S. Food and Drug Administration approval after phase I. This article reviews recent innovations in phase I design from the perspective of multiple stakeholders and provides recommendations for future trials.

PMID:34061563 | DOI:10.1200/EDBK_319783