-
NeuroImage Nov 2017Diffusion tensor imaging (DTI) is a well-established magnetic resonance imaging (MRI) technique used for studying microstructural changes in the white matter. As with...
Diffusion tensor imaging (DTI) is a well-established magnetic resonance imaging (MRI) technique used for studying microstructural changes in the white matter. As with many other imaging modalities, DTI images suffer from technical between-scanner variation that hinders comparisons of images across imaging sites, scanners and over time. Using fractional anisotropy (FA) and mean diffusivity (MD) maps of 205 healthy participants acquired on two different scanners, we show that the DTI measurements are highly site-specific, highlighting the need of correcting for site effects before performing downstream statistical analyses. We first show evidence that combining DTI data from multiple sites, without harmonization, may be counter-productive and negatively impacts the inference. Then, we propose and compare several harmonization approaches for DTI data, and show that ComBat, a popular batch-effect correction tool used in genomics, performs best at modeling and removing the unwanted inter-site variability in FA and MD maps. Using age as a biological phenotype of interest, we show that ComBat both preserves biological variability and removes the unwanted variation introduced by site. Finally, we assess the different harmonization methods in the presence of different levels of confounding between site and age, in addition to test robustness to small sample size studies.
Topics: Adolescent; Adult; Autism Spectrum Disorder; Child; Cohort Studies; Diffusion Tensor Imaging; Female; Humans; Image Processing, Computer-Assisted; Male; Multicenter Studies as Topic; White Matter; Young Adult
PubMed: 28826946
DOI: 10.1016/j.neuroimage.2017.08.047 -
Sultan Qaboos University Medical Journal Feb 2020This study aimed to examine the proportion of needle stick and sharp injuries (NSSIs) among healthcare workers at King Hussein Medical Center (KHMC), Amman, Jordan.
OBJECTIVES
This study aimed to examine the proportion of needle stick and sharp injuries (NSSIs) among healthcare workers at King Hussein Medical Center (KHMC), Amman, Jordan.
METHODS
All NSSI reports referred from departments at KHMC to the Preventive Medicine Department between 2013-2018 were retrospectively reviewed. Proportion of NSSIs were calculated and stratified according to age, gender, job title, place and site of injury and the procedure/task during which the injury occurred.
RESULTS
There were a total of 393 NSSIs. A significant association was found between the proportion of NSSIs and all tested variables ( <0.001). The reported proportion of NSSIs was highest among nurses (39.7%) followed by cleaners (36.3%), physicians (10.4%), other workers (7.4%) and lab technicians (5.9%) during the study's six-year period. Hospital wards were the most common locations (46.1%) where injuries took place. Injuries also occurred most frequently during medical waste collection (38.2%).
CONCLUSION
The proportion of NSSIs was highest among nurses and cleaners. Safety policies and training among high-risk groups should be reviewed to reduce the risk of NSSIs. Multicentre studies at a national level should be conducted to examine whether this study's findings reflect national trends.
Topics: Adult; Female; Health Personnel; Housekeeping, Hospital; Humans; Jordan; Male; Middle Aged; Needlestick Injuries; Nursing Staff, Hospital; Occupational Injuries; Retrospective Studies; Risk Factors; Young Adult
PubMed: 32190370
DOI: 10.18295/squmj.2020.20.01.008 -
Neuroscience Insights 2021Intraspecies aggression is commonly focused on securing reproductive resources such as food, territory, and mates, and it is often males who do the fighting. In humans,... (Review)
Review
Intraspecies aggression is commonly focused on securing reproductive resources such as food, territory, and mates, and it is often males who do the fighting. In humans, individual acts of overt physical aggression seem maladaptive and probably represent dysregulation of the pathways underlying aggression. Such acts are often associated with ethanol consumption. The model system, which has long been used to study how ethanol affects the nervous system and behavior, has also been used to study the molecular origins of aggression. In addition, ethanol-induced aggression has been demonstrated in flies. Recent publications show that ethanol stimulates Drosophila aggression in 2 ways: the odor of ethanol and the consumption of ethanol both make males more aggressive. These ethanol effects occur at concentrations that flies likely experience in the wild. A picture emerges of males arriving on their preferred reproductive site-fermenting plant matter-and being stimulated by ethanol to fight harder to secure the site for their own use. Fly fighting assays appear to be a suitable bioassay for studying how low doses of ethanol reshape neural signaling.
PubMed: 34841248
DOI: 10.1177/26331055211061145 -
Cureus Oct 2023With the burgeoning numbers of clinical trials, the competition among sponsors for research subjects has grown intensely. Many clinical trials fail to meet their...
With the burgeoning numbers of clinical trials, the competition among sponsors for research subjects has grown intensely. Many clinical trials fail to meet their recruitment goals. Contract research organizations (CROs) that help conduct all or portions of a clinical study have transitioned from highly specialized niches, such as biostatistical analysis or regulatory compliance, to more overall functions to keep a trial moving forward. CROs establish agreements with sponsors, including how much a site will be paid per study subject. CROs are locked into that pricing, but over the course of a study's recruitment period, sponsors with deeper pockets may step in and offer more compensation per subject. The result is a competitive market place that favors big sponsors and puts smaller CROs and start-ups at a disadvantage.
PubMed: 38022306
DOI: 10.7759/cureus.47819 -
International Journal of Molecular... Jan 2023Studying individual data types in isolation provides only limited and incomplete answers to complex biological questions and particularly falls short in revealing... (Review)
Review
Studying individual data types in isolation provides only limited and incomplete answers to complex biological questions and particularly falls short in revealing sufficient mechanistic and kinetic details. In contrast, multi-omics approaches to studying health and disease permit the generation and integration of multiple data types on a much larger scale, offering a comprehensive picture of biological and disease processes. Gastroenterology and hepatobiliary research are particularly well-suited to such analyses, given the unique position of the luminal gastrointestinal (GI) tract at the nexus between the gut (mucosa and luminal contents), brain, immune and endocrine systems, and GI microbiome. The generation of 'big data' from multi-omic, multi-site studies can enhance investigations into the connections between these organ systems and organisms and more broadly and accurately appraise the effects of dietary, pharmacological, and other therapeutic interventions. In this review, we describe a variety of useful omics approaches and how they can be integrated to provide a holistic depiction of the human and microbial genetic and proteomic changes underlying physiological and pathophysiological phenomena. We highlight the potential pitfalls and alternatives to help avoid the common errors in study design, execution, and analysis. We focus on the application, integration, and analysis of big data in gastroenterology and hepatobiliary research.
Topics: Humans; Proteomics; Genomics; Epigenomics; Metabolomics; Gastroenterology
PubMed: 36768780
DOI: 10.3390/ijms24032458 -
Chemical Science Dec 2022Biomolecular phase transitions play an important role in organizing cellular processes in space and time. Methods and tools for studying these transitions, and the... (Review)
Review
Biomolecular phase transitions play an important role in organizing cellular processes in space and time. Methods and tools for studying these transitions, and the intrinsically disordered proteins (IDPs) that often drive them, are typically less developed than tools for studying their folded protein counterparts. In this perspective, we assess the current landscape of chemical tools for studying IDPs, with a specific focus on protein liquid-liquid phase separation (LLPS). We highlight methodologies that enable imaging and spectroscopic studies of these systems, including site-specific labeling with small molecules and the diverse range of capabilities offered by inteins and protein semisynthesis. We discuss strategies for introducing post-translational modifications that are central to IDP and LLPS function and regulation. We also investigate the nascent field of noncovalent small-molecule modulators of LLPS. We hope that this review of the state-of-the-art in chemical tools for interrogating IDPs and LLPS, along with an associated perspective on areas of unmet need, can serve as a valuable and timely resource for these rapidly expanding fields of study.
PubMed: 36545140
DOI: 10.1039/d2sc04907d -
JACS Au Jan 2022O-GlcNAcylation is a dynamic post-translational modification which affects myriad proteins, cellular functions, and disease states. Its presence or absence modulates... (Review)
Review
O-GlcNAcylation is a dynamic post-translational modification which affects myriad proteins, cellular functions, and disease states. Its presence or absence modulates protein function via differential protein- and site-specific mechanisms, necessitating innovative techniques to probe the modification in highly selective manners. To this end, a variety of biological and chemical methods have been developed to study specific O-GlcNAc modification events both and , each with their own respective strengths and shortcomings. Together, they comprise a potent chemical biology toolbox for the analysis of O-GlcNAcylation (and, in theory, other post-translational modifications) while highlighting the need and space for more facile, generalizable, and biologically authentic techniques.
PubMed: 35098223
DOI: 10.1021/jacsau.1c00455 -
Infectious Medicine Jun 2023Tuberculosis is a disease of great relevance since it is one of the leading causes of morbidity and mortality worldwide. Gastrointestinal tuberculosis is an unusual...
BACKGROUND
Tuberculosis is a disease of great relevance since it is one of the leading causes of morbidity and mortality worldwide. Gastrointestinal tuberculosis is an unusual presentation. It is defined as the involvement of any segment of the digestive tract, associated viscera, and peritoneum. The study's main objective is to collect information from autopsies of patients diagnosed with gastrointestinal tuberculosis in a Pathology reference center in Colombia.
METHODS
This is a retrospective and descriptive study of autopsy reports. A total of 4,500 autopsies were performed between January 2004 and December 2020. The inclusion criteria were authorization of a family member following local law regulations and a final autopsy diagnosis of gastrointestinal tuberculosis using microscopic visualization.
RESULTS
Forty-eight patients with gastrointestinal tuberculosis autopsies were included in our study. Most of the patients were male ( = 35, 72.9%) with a median age of 40.5 years old. Human immunodeficiency virus infection history was reported in 28 cases (58.33%). The most affected gastrointestinal tract site was the terminal ileum. Ulcers and thickened epithelium were common autopsies macroscopic findings. Tuberculosis multiorgan compromise was a relevant finding in patients with gastrointestinal tuberculosis.
CONCLUSIONS
Gastrointestinal tuberculosis is a disease of great importance, being its diagnosis a clinical challenge. Underdiagnosis can be reported in a high percentage of cases, so autopsy diagnosis can help reveal more accurate data about this condition.
PubMed: 38077832
DOI: 10.1016/j.imj.2023.04.007 -
RNA Biology 2018Posttranslational modification (PTM) is a key mechanism for regulating diverse protein functions, and thus critically affects many essential biological processes.... (Review)
Review
Posttranslational modification (PTM) is a key mechanism for regulating diverse protein functions, and thus critically affects many essential biological processes. Critical for systematic study of the effects of PTMs is the ability to obtain recombinant proteins with defined and homogenous modifications. To this end, various synthetic and chemical biology approaches, including genetic code expansion and protein chemical modification methods, have been developed. These methods have proven effective for generating site-specific authentic modifications or structural mimics, and have demonstrated their value for in vitro and in vivo functional studies of diverse PTMs. This review will discuss recent advances in chemical biology strategies and their application to various PTM studies.
Topics: Acetylation; Chemistry Techniques, Synthetic; Codon, Terminator; Genetic Code; Glycosylation; Humans; Lysine; Methylation; Nitrates; Phosphorylation; Protein Processing, Post-Translational; Proteome; Selenocysteine; Sulfates; Ubiquitination
PubMed: 28901832
DOI: 10.1080/15476286.2017.1360468 -
Protein Science : a Publication of the... Apr 2023Post-translational modifications (PTMs) of proteins not only exponentially increase the diversity of proteoforms, but also contribute to dynamically modulating the... (Review)
Review
Post-translational modifications (PTMs) of proteins not only exponentially increase the diversity of proteoforms, but also contribute to dynamically modulating the localization, stability, activity, and interaction of proteins. Understanding the biological consequences and functions of specific PTMs has been challenging for many reasons, including the dynamic nature of many PTMs and the technical limitations to access homogenously modified proteins. The genetic code expansion technology has emerged to provide unique approaches for studying PTMs. Through site-specific incorporation of unnatural amino acids (UAAs) bearing PTMs or their mimics into proteins, genetic code expansion allows the generation of homogenous proteins with site-specific modifications and atomic resolution both in vitro and in vivo. With this technology, various PTMs and mimics have been precisely introduced into proteins. In this review, we summarize the UAAs and approaches that have been recently developed to site-specifically install PTMs and their mimics into proteins for functional studies of PTMs.
Topics: Proteins; Protein Processing, Post-Translational; Amino Acids; Genetic Code; Codon
PubMed: 36883310
DOI: 10.1002/pro.4618