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Journal of Applied Statistics 2024Proportional data arise frequently in a wide variety of fields of study. Such data often exhibit extra variation such as over/under dispersion, sparseness and zero...
Proportional data arise frequently in a wide variety of fields of study. Such data often exhibit extra variation such as over/under dispersion, sparseness and zero inflation. For example, the hepatitis data present both sparseness and zero inflation with 19 contributing non-zero denominators of 5 or less and with 36 having zero seropositive out of 83 annual age groups. The whitefly data consists of 640 observations with 339 zeros (53%), which demonstrates extra zero inflation. The catheter management data involve excessive zeros with over 60% zeros averagely for outcomes of 193 urinary tract infections, 194 outcomes of catheter blockages and 193 outcomes of catheter displacements. However, the existing models cannot always address such features appropriately. In this paper, a new two-parameter probability distribution called Lindley-binomial (LB) distribution is proposed to analyze the proportional data with such features. The probabilistic properties of the distribution such as moment, moment generating function are derived. The Fisher scoring algorithm and EM algorithm are presented for the computation of estimates of parameters in the proposed LB regression model. The issues on goodness of fit for the LB model are discussed. A limited simulation study is also performed to evaluate the performance of derived EM algorithms for the estimation of parameters in the model with/without covariates. The proposed model is illustrated through three aforementioned proportional datasets.
PubMed: 38933142
DOI: 10.1080/02664763.2023.2237212 -
Microbiology and Immunology Jun 2024The tumor microenvironment of hepatoblastoma (HB), the most common pediatric liver tumor, predominantly exhibits a myeloid immune landscape. in which tumor-associated... (Review)
Review
The tumor microenvironment of hepatoblastoma (HB), the most common pediatric liver tumor, predominantly exhibits a myeloid immune landscape. in which tumor-associated macrophages (TAMs) are considered the core component. The crosstalk between TAMs and HB cells markedly influences tumor behavior. TAM-derived factors are involved in tumor proliferation and vascular invasion. On the other hand, HB cell secretome attracts, stimulates, and reprograms TAMs to be immunosuppressive in favor of tumor invasion, rather than their innate role in combating tumor growth, such crosstalk sometimes forms bidirectional feedback loops, making the tumor more virulent and resistant to routine therapeutics. Consequently, TAMs are the common denominator of most suggested HB immunotherapeutic strategies. Macrophage immune checkpoint inhibitors, macrophage-mediated antibody-dependent cellular phagocytosis, and the novel chimeric antigen receptor macrophage therapy (CAR Mφ) are currently under trial. In this review, we will summarize the significance of TAMs and their potential role as a therapeutic target in HB.
PubMed: 38923004
DOI: 10.1111/1348-0421.13162 -
JAMA Jun 2024Hospitals are hot zones of the US gun injury epidemic. To shelter these facilities from the dangers of gun violence, state legislatures have enacted laws to reduce the...
IMPORTANCE
Hospitals are hot zones of the US gun injury epidemic. To shelter these facilities from the dangers of gun violence, state legislatures have enacted laws to reduce the carrying of firearms on hospital premises. However, these efforts currently face serious Second Amendment challenges in federal courts. The ongoing legal battles, which have wide-ranging implications for patient and clinician safety as well as public health generally, are setting the stage for a Supreme Court case that may decide the fate of firearm regulations in US hospitals. A permissible pathway for advancing sensible gun regulation in hospitals is urgently needed.
OBSERVATIONS
Since the Supreme Court established a new constitutional test for firearm laws in New York State Rifle & Pistol Association v Bruen (2022), states now face unprecedentedly high barriers to enacting health-protecting legislation regarding firearms. Post-Bruen, the Supreme Court requires that laws be consistent with "this Nation's historical tradition of firearms regulation." This means that states hoping to enact laws barring public carry of firearms in hospitals must demonstrate that hospitals are a "sensitive place" as a historical matter (ie, analogous to a location where firearms were traditionally restricted). By reasoning from analogy, it is clear several historical comparators exist for regulating firearms in hospitals. Although the hospital (as understood today) did not exist in the 1700s, it is sufficiently analogous to asylums and schools, to name a few examples. These settings all share a common denominator with the modern-day hospital: serving vulnerable populations or individuals who may be at heightened risk of misusing firearms.
CONCLUSIONS AND RELEVANCE
The Supreme Court's interpretation of the Second Amendment right to bear arms is threatening democratically enacted laws seeking to shelter hospitals from firearm violence. However, it is clear that hospitals and other health care settings are a sensitive place with compelling historical analogies. Policymakers' strategic deployment of the sensitive places designation, along with its rightful judicial recognition in the hospital setting, are critical to upholding laws that protect health care facilities, patients, and professionals from firearm violence-a conclusion consistent with the US Constitution, history, medical ethics, and common sense.
PubMed: 38922303
DOI: 10.1001/jama.2024.9994 -
PloS One 2024Making data FAIR-findable, accessible, interoperable, reproducible-has become the recurring theme behind many research data management efforts. dtool is a lightweight...
Making data FAIR-findable, accessible, interoperable, reproducible-has become the recurring theme behind many research data management efforts. dtool is a lightweight data management tool that packages metadata with immutable data to promote accessibility, interoperability, and reproducibility. Each dataset is self-contained and does not require metadata to be stored in a centralised system. This decentralised approach means that finding datasets can be difficult. dtool's lookup server, short dserver, as defined by a REST API, makes dtool datasets findable, hence rendering the dtool ecosystem fit for a FAIR data management world. Its simplicity, modularity, accessibility and standardisation via API distinguish dtool and dserver from other solutions and enable it to serve as a common denominator for cross-disciplinary research data management. The dtool ecosystem bridges the gap between standardisation-free data management by individuals and FAIR platform solutions with rigid metadata requirements.
Topics: Software; Data Management; Metadata; Ecosystem; Reproducibility of Results; Internet
PubMed: 38917182
DOI: 10.1371/journal.pone.0306100 -
Methods in Molecular Biology (Clifton,... 2024Based on classical karyotyping, structural genome variations (SVs) have generally been considered to be either "simple" (with one or two breakpoints) or "complex" (with... (Review)
Review
Based on classical karyotyping, structural genome variations (SVs) have generally been considered to be either "simple" (with one or two breakpoints) or "complex" (with more than two breakpoints). Studying the breakpoints of SVs at nucleotide resolution revealed additional, subtle structural variations, such that even "simple" SVs turned out to be "complex." Genome-wide sequencing methods, such as fosmid and paired-end mapping, short-read and long-read whole genome sequencing, and single-molecule optical mapping, also indicated that the number of SVs per individual was considerably larger than expected from karyotyping and high-resolution chromosomal array-based studies. Interestingly, SVs were detected in studies of cohorts of individuals without clinical phenotypes. The common denominator of all SVs appears to be a failure to accurately repair DNA double-strand breaks (DSBs) or to halt cell cycle progression if DSBs persist. This review discusses the various DSB response mechanisms during the mitotic cell cycle and during meiosis and their regulation. Emphasis is given to the molecular mechanisms involved in the formation of translocations, deletions, duplications, and inversions during or shortly after meiosis I. Recently, CRISPR-Cas9 studies have provided unexpected insights into the formation of translocations and chromothripsis by both breakage-fusion-bridge and micronucleus-dependent mechanisms.
Topics: Humans; Genomic Structural Variation; DNA Breaks, Double-Stranded; Meiosis; Karyotyping; CRISPR-Cas Systems; Animals
PubMed: 38913302
DOI: 10.1007/978-1-0716-3946-7_2 -
Trends in Cell Biology Jun 2024To face genotoxic stress, eukaryotic cells evolved extremely refined mechanisms. Defects in counteracting the threat imposed by DNA damage underlie the rare disease... (Review)
Review
To face genotoxic stress, eukaryotic cells evolved extremely refined mechanisms. Defects in counteracting the threat imposed by DNA damage underlie the rare disease Cockayne syndrome (CS), which arises from mutations in the CSA and CSB genes. Although initially defined as DNA repair proteins, recent work shows that CSA and CSB act instead as master regulators of the integrated response to genomic stress by coordinating DNA repair with transcription and cell division. CSA and CSB exert this function through the ubiquitination of target proteins, which are effectors/regulators of these processes. This review describes how the ubiquitination of target substrates is a common denominator by which CSA and CSB participate in different aspects of cellular life and how their mutation gives rise to the complex disease CS.
PubMed: 38910038
DOI: 10.1016/j.tcb.2024.06.002 -
Frontiers in Public Health 2024Cataract surgery and laser peripheral iridotomy (LPI) are effective approaches for preventing primary angle closure diseases (PACDs), as well as acute primary angle...
BACKGROUND
Cataract surgery and laser peripheral iridotomy (LPI) are effective approaches for preventing primary angle closure diseases (PACDs), as well as acute primary angle closure (APAC). Due to the development of population screening and increases in cataract surgery rates, this study aimed to examine trends in the admission rates of PACD among the urban population in China.
METHODS
This cross-sectional study examined patients who were admitted to a hospital for PACD, and who underwent cataract surgery or LPI operations. The data were obtained from the Yinzhou Regional Health Information Platform (YRHIP) from 2011 to 2021. The annual rates of PACD and APAC admissions, cataract surgery and LPI were analyzed, with the number of cases used as numerators and the annual resident population in Yinzhou district used as denominators.
RESULTS
A total of 2,979 patients with PACD admissions, 1,023 patients with APAC admissions, 53,635 patients who underwent cataract surgery and 16,450 patients who underwent LPI were included. The number of annual admissions for PACD gradually increased from 22 cases (1.6/100000) in 2011 to 387 cases (30.8/100000) in 2016, after which it decreased to 232 cases (16.2/100000) in 2019 and then increased to 505 cases (30.6/100000) in 2021. The number of cataract surgeries gradually increased from 1728 (127.7/100000) in 2011 to 7002 (424.9/100000) in 2021. Similarly, the number of LPI gradually increased from 109 (8.0/100000) in 2011 to 3704 (224.8/100000) in 2021.
CONCLUSION
The admission rates of PACD for the urban population in China have declined in recent years after a long increasing trend in the rates of cataract surgery and LPI. However, it increased rapidly during the COVID-19 epidemic. The national health database should be further utilized to investigate temporal trends in the prevalence of PACD.
Topics: Humans; Glaucoma, Angle-Closure; China; Cross-Sectional Studies; Male; Female; Aged; Cataract Extraction; Middle Aged; Urban Population; Hospitalization; Aged, 80 and over; Adult; Patient Admission
PubMed: 38903596
DOI: 10.3389/fpubh.2024.1398674 -
Vox Sanguinis Jun 2024Haemovigilance (HV) systems aim to improve transfusion outcomes in patients and donor safety. An important question for blood regulators is how to ensure an effective HV...
BACKGROUND AND OBJECTIVES
Haemovigilance (HV) systems aim to improve transfusion outcomes in patients and donor safety. An important question for blood regulators is how to ensure an effective HV system.
MATERIALS AND METHODS
We retrospectively analysed the HV reports submitted to Paul-Ehrlich-Institut over the last two decades.
RESULTS
Between 2011 and 2020, 50.86 million units of blood components were used, and 8931 suspected serious donor and recipient adverse reactions (SARs), 874 serious adverse events (SAEs) and 12,073 donor look-backs were reported. Following implementation of specific risk-minimization measures (RMMs) between 2000 and 2010, SAR reporting rates decreased for transfusion-transmitted viral infections (TTVIs), transfusion-related acute lung injury (TRALI) and transfusion-transmitted bacterial infections (TTBIs), while increasing for other serious adverse transfusion reactions. Within this decade, the overall blood component use decreased.
CONCLUSION
Long-term data collection forms the basis to establish trends and changes in reporting and to evaluate the effect of RMM. Standardized criteria for reaction types, seriousness and imputability assessments and availability of a denominator are important elements. Central data collection and independent assessment allow for monitoring HV data in a nationwide context over time. Stakeholder involvement and transparent feedback on the benefit of RMM will help to achieve the objectives of HV.
PubMed: 38889998
DOI: 10.1111/vox.13694 -
Molecular Biology of the Cell Jun 2024Maintenance of a pool of active lysosomes with acidic pH and degradative hydrolases is crucial for cell health. Abnormalities in lysosomal function are closely linked to...
Maintenance of a pool of active lysosomes with acidic pH and degradative hydrolases is crucial for cell health. Abnormalities in lysosomal function are closely linked to diseases, such as lysosomal storage disorders (LSDs), neurodegeneration, intracellular infections, and cancer among others. Emerging body of research suggests the malfunction of lysosomal hydrolase trafficking pathway to be a common denominator of several disease pathologies. However, available conventional tools to assess lysosomal hydrolase trafficking are insufficient and fail to provide a comprehensive picture about the trafficking flux and location of lysosomal hydrolases. To address some of the shortcomings, we designed a genetically encoded fluorescent reporter containing a lysosomal hydrolase tandemly tagged with pH sensitive and insensitive fluorescent proteins, which can spatio-temporally trace the trafficking of lysosomal hydrolases. As a proof of principle, we demonstrate that the reporter can detect perturbations in hydrolase trafficking, that are induced by pharmacological manipulations and pathophysiological conditions like intracellular protein aggregates. This reporter can effectively serve as a probe for mapping the mechanistic intricacies of hydrolase trafficking pathway in health and disease and is a utilitarian tool to identify genetic and pharmacological modulators of this pathway, with potential therapeutic implications.
PubMed: 38888935
DOI: 10.1091/mbc.E23-09-0344 -
Cellular Oncology (Dordrecht) Jun 2024Gynecomastia denotes the benign proliferation of glandular breast tissue and stands as a recognized risk factor for male breast cancer. Nonetheless, the underlying...
BACKGROUND
Gynecomastia denotes the benign proliferation of glandular breast tissue and stands as a recognized risk factor for male breast cancer. Nonetheless, the underlying carcinogenic mechanisms orchestrating the progression from gynecomastia to cancer remain poorly understood.
METHODS
This study employed single-cell RNA sequencing (scRNA-seq) to meticulously dissect the cellular landscape of gynecomastia and unravel potential associations with male breast cancer at a single-cell resolution. Pseudotime and evolutionary analyses were executed to delineate the distinct features characterizing gynecomastia and male breast cancer. The TCGA database, along with cell-cell communication analysis and immunohistochemistry staining, was harnessed to validate differential gene expression, specifically focusing on CD13.
RESULT
From the copy number variation profiles and evolutionary tree, we inferred shared mutation characteristics (18p and 18q) underpinning both conditions. The developmental trajectory unveiled an intriguing overlap between gynecomastia and malignant epithelial cells. Moreover, the differential gene CD13 emerged as a common denominator in both gynecomastia and male breast cancer when compared with normal mammary tissue. Cell-cell interaction analysis and communication dynamics within the tumor microenvironment spotlighted distinctions between CD13 and CD13 subsets, with the former exhibiting elevated expression of FGFR1-FGF7.
CONCLUSIONS
Our investigation provides novel insights into the evolutionary progression from gynecomastia to male breast cancer, shedding light on the pivotal role of CD13 in driving this transition. The identification of CD13 as a potential therapeutic target suggests the feasibility of CD13-targeted interventions, specifically tailored for male breast cancer treatment.
PubMed: 38888848
DOI: 10.1007/s13402-024-00964-4