MIMIC-III (‘Medical Information Mart for Intensive Care’) is a large, single-center database comprising information relating to patients admitted to critical care units at a large tertiary care hospital. Data includes vital signs, medications, laboratory measurements, observations and notes charted by care providers, fluid balance, procedure codes, diagnostic codes, imaging reports, hospital length of stay, survival data, and more. The database supports applications including academic and industrial research, quality improvement initiatives, and higher education coursework. Design Type(s) data integration objective Measurement Type(s) Demographics • clinical measurement • intervention • Billing • Medical History Dictionary • Pharmacotherapy • clinical laboratory test • medical data Technology Type(s) Electronic Medical Record • Medical Record • Electronic Billing System • Medical Coding Process Document • Free Text Format Factor Type(s) Sample Characteristic(s) Homo sapiens Design Type(s) data integration objective Measurement Type(s) Demographics • clinical measurement • intervention • Billing • Medical History Dictionary • Pharmacotherapy • clinical laboratory test • medical data Technology Type(s) Electronic Medical Record • Medical Record • Electronic Billing System • Medical Coding Process Document • Free Text Format Factor Type(s) Sample Characteristic(s) Homo sapiens Machine-accessible metadata file describing the reported data (ISA-Tab format)
Optical coherence tomography (OCT) is an emerging technology for performing high-resolution cross-sectional imaging. OCT is analogous to ultrasound imaging, except that it uses light instead of sound. OCT can provide cross-sectional images of tissue structure on the micron scale in situ and in real time. Using OCT in combination with catheters and endoscopes enables high-resolution intraluminal imaging of organ systems. OCT can function as a type of optical biopsy and is a powerful imaging technology for medical diagnostics because unlike conventional histopathology which requires removal of a tissue specimen and processing for microscopic examination, OCT can provide images of tissue in situ and in real time. OCT can be used where standard excisional biopsy is hazardous or impossible, to reduce sampling errors associated with excisional biopsy, and to guide interventional procedures. In this paper, we review OCT technology and describe its potential biomedical and clinical applications.
Abstract Background Post-COVID-19 syndrome (PCS) affects around 10% of individuals who experience SARS-CoV-2 infection worldwide. This four-year follow-up study investigated the long-term impact of mesenchymal stromal cell (MSC) therapy on both the occurrence of PCS and its underlying mechanisms. Methods We enrolled 148 survivors of severe COVID-19 (92 who received MSC therapy and 56 who served as controls). The clinical evaluations included safety (new-onset comorbidities, oncogenic risk) and efficacy outcomes (computed tomography [CT] imaging, functional capacity, pulmonary function, 36-Item Short-Form Survey [SF-36], PCS prevalence). Serum proteomic profiling was performed to identify the differentially expressed proteins (DEPs) across the PCS subtypes, including chronic fatigue-like syndrome (CFs), respiratory syndrome (REs), chronic pain syndrome (CPs), and neurosensorial syndrome (NSs). Results MSC therapy had a favorable long-term safety profile. The overall prevalence of PCS was 73.6% (109/148), with CFs being the most common subtype (50.7%, 75/148). Moreover, the incidence of CFs was significantly lower in the MSC group than in the control group (41.3% vs. 66.1%; odds ratio = 0.361, p = 0.003). MSC therapy was also associated with a significant improvement in the SF-36 Role-Emotional domain. No significant differences were observed in the participants’ CT outcomes, functional capacity, or pulmonary function. A predictive model integrating proteomic and clinical data for CFs achieved an area under the curve of 0.773. Unsupervised clustering identified three molecular endotypes, with one being both highly enriched for respiratory syndrome and characterized by dysregulated immune pathways. Conclusion This 4-year follow-up shows a sustained association between MSC therapy and a lower likelihood of CFs in severe COVID-19 survivors, with a favorable safety profile. Integrated proteomic and clinical analysis reveals distinct biological pathways underpinning PCS heterogeneity, suggesting potential biological bases underlying the subtype-specific associations observed with MSC therapy and highlighting potential targets for future precision medicine approaches.
Virus-induced antibodies represent a dual-edged sword in the immune response to viral infections. While antibodies are critical for neutralizing pathogens, some can paradoxically exacerbate disease severity through mechanisms such as antibody-dependent enhancement (ADE), autoantibody, and prolonged inflammation. Long coronavirus disease (COVID) and dengue hemorrhagic fever (DHF) exemplify conditions where pathogenic antibodies play a pivotal role in disease progression. Long COVID is associated with persistent immune dysregulation and autoantibody production, leading to chronic symptoms and tissue damage. In DHF, pre-existing antibodies against dengue virus contribute to ADE, amplifying viral replication, immune activation, and vascular permeability. This review explores the mechanisms underlying these pathogenic antibody responses, highlighting the shared pathways of immune dysregulation and comparing the distinct features of both conditions. By examining these studies, we identify key lessons for therapeutic strategies, vaccine design, and future research aimed at mitigating the severe outcomes of viral infections.
Background:
This study aimed to investigate the effects of combining an ilioinguinal/iliohypogastric nerve block with an ultrasound-guided quadratus lumborum block during inguinal surgery in older patients.
Methods:
Between December 2020 and June 2023, 300 elderly patients who underwent inguinal surgery at our institution were randomly divided into an observation group (n = 150) and a control group (n = 150). The observation group received ultrasound-guided quadratus lumborum block in addition to ilioinguinal/iliohypogastric nerve block, whereas the control group received only ultrasound-guided ilioinguinal/iliohypogastric nerve block. The postoperative conditions and anesthesia dose (propofol and remifentanil) during surgery were recorded. The average arterial pressure and heart rate of the two groups were compared 10 min before anesthesia, 10 min after anesthesia, and postoperatively. Pain intensity was measured during and 30 min after the procedure using the pain Visual Analog Scale (VAS). The levels of malondialdehyde (MDA), aldosterone (ALD), and total antioxidant capacity (TAC) were evaluated before surgery and 1 day later, and the incidence of postoperative complications was noted and compared between the two groups.
Results:
The propofol and remifentanil dosages in the observation group were much lower than those in the control group, and hospital stay and recovery times were significantly shorter (P < 0.05). Ten minutes before anesthesia, there was no significant difference in the mean arterial pressure and heart rate between the two groups, and no difference at any other time point in the observation group (P > 0.05). Ten minutes after anesthesia and postoperatively, the average arterial pressure and heart rate of the observation group were lower than those of the control group, whereas those of the control group were higher than those observed preanesthesia (P < 0.05). The postoperative MDA and ALD levels in the observation group were significantly higher than those in the control group (P < 0.05), and the postoperative TAC level in the observation group was significantly lower than that in the control group (P < 0.05). The VAS scores in the observation group were significantly lower than those in the control group. No discernible difference in the frequency of complications was observed between the two groups (P > 0.05).
Conclusion:
The combination of ilioinguinal/iliohypogastric nerve block with ultrasound-guided quadratus lumborum block can significantly minimize the amount of anesthesia used during surgery, exert a good analgesic effect, shorten hospitalization time, stabilize hemodynamics, and reduce stress response with high safety.
Abstract As the prevalence of metabolic diseases such as diabetes and obesity continue to rise, the search for more effective and convenient treatments has become a crucial issue in medical research. Microneedles (MNs), as an innovative drug delivery system, have shown advantages in the treatment of metabolic diseases in recent years. MNs-based drug delivery system, which use MNs to deliver drugs directly to the subcutaneous tissue, improve drug bioavailability and reduce systemic side effects. This review aims to summarize the latest concepts, designs, and types of MNs, and to investigate the materials and manufacturing methods used in their construction. Subsequently, the mechanisms of drug delivery and graded release of MNs and recent research progress are further summarized. This article focuses on the application of MNs in the treatment of common metabolic diseases, with a special emphasis on the progress and optimization of diabetic and anti-obesity MNs. The main challenges and future perspectives in the production and evaluation of MNs, as well as in enhancing treatment efficacy and improving safety, are elucidated.
IntroductionIntersectionality recognizes and maps the ways oppressions interact and intersect for multiply marginalized people. This framework is a pushing back against the historical approach to discrimination that has taken a “single-axis” view of discrimination, focusing on one single type of oppression, even for people with multiple identities. Little attention has been drawn to intersectionality when it comes to disability, especially related to disability and race.ObjectiveIn recognition of the intersectional nature of ableism and racism, the aim of this study was to develop and validate the Symbolic Intersecting Ableism and Racism Scale (SIARS).Materials and methodsWe piloted the SIARS with 512 people (July-October 2024) and conducted an exploratory factor analysis to examine the underlying structure of the SIARS.ResultsThe SIARS has adequate validity and reliability. Our findings suggest the SIARS is comprised of a complex combination of a denial of continuing discrimination, individualism, and empathy. The findings also indicated many points of contention with the single-axis symbolic ableism scale measure, which examines disability only, further reinforcing the need to measure and attend to intersectionality.ConclusionWithout doing so, we will never truly be able to dismantle oppression and discrimination, including the ableism disabled people face.
Mesk Alkhatib, Noor Almasri, Sakhr Alshwayyat
et al.
Semaglutide, a GLP-1 receptor agonist, is FDA-approved for managing type 2 diabetes (T2D) and reducing cardiovascular risk. Its off-label use in weight management and other conditions has grown, prompting a review of its benefits and risks. This review evaluates evidence on semaglutide’s effects, highlighting its therapeutic potential beyond approved indications. Studies from 2021–2024 were reviewed via PubMed, ScienceDirect, and Google Scholar. Semaglutide showed promise in managing PCOS-related obesity, insulin resistance, and demonstrated renoprotective effects in diabetics and chronic kidney disease (CKD). Additionally, it improves liver enzyme levels, steatosis, and stiffness, aiding in managing Nonalcoholic Fatty Liver Disease and Nonalcoholic Steatohepatitis in non-fibrotic patients. The FDA has approved it for reducing major adverse cardiovascular events, heart failure symptoms, and physical limitations in diabetic and non-diabetics. Preclinical studies suggest benefits in cognitive disorders associated with insulin resistance, including Alzheimer’s disease, Parkinson’s disease, and vascular dementia in animals. Although rare cases of thyroid cancer have been reported, no causal relationship has been established, emphasizing the need of caution in high-risk populations. GLP-1 therapy has also exerted protective effects against the risk of various types of cancer. However, ongoing human studies are essential to validate these findings and clarify semaglutide’s association with cancer.
Joanna Maria Jasińska, Klaudia Michalska, Joanna Tkaczewska
et al.
Novel double-layer films based on furcellaran (FUR) and gelatin (GEL) with the addition of <i>Phytolacca americana</i> L. (PA) extract were used as active packaging for African catfish fillets. Films with PA extract have been shown to minimize the catfish spoilage effects, expressed as odor reduction compared to control samples; however, neither the films nor the PA extract exhibited antimicrobial activity against tested groups of microorganisms (fungi, lactic acid bacteria, <i>Enterobacterales</i> and psychrotrops) or specified microorganisms (<i>E. coli</i>, <i>S. aureus</i>, <i>S. cerevisiae</i>). The tested films demonstrated antioxidant activity determined by the DPPH, ABTS, FRAP, CUPRAC and Folin–Ciocâlteu methods. Cytotoxicity analysis showed that the PA extract affected tested cell lines (PNT2—prostate epithelial cells, HepG2—human liver cells, HaCaT—normal human keratinocytes and Nty-hori 3-1) only to a small extent—the calculated IC<sub>50</sub> values exceeded the maximal tested concentration of 500 µg/mL.
Archana Kamalakar, Brendan Tobin, Sundus Kaimari
et al.
Current treatments for congenital and acquired craniofacial (CF) bone abnormalities are limited and costly. Conventional methods involve surgical correction, short-term stabilization, and long-term bone grafting, which may include problematic allografts and limited autografts. While bone morphogenetic protein 2 (BMP2) has been used for bone regeneration, it can cause bone overgrowth and life-threatening inflammation. Bone marrow-derived mesenchymal stem cell therapies, though promising, are not Food and Drug Administration approved and are resource intensive. Thus, there is a need for effective, affordable, and less side-effect-prone bone regenerative therapies. Previous research demonstrated that JAGGED1 induces osteoblast commitment in murine cranial neural crest cells through a NOTCH-dependent non-canonical pathway involving JAK2–STAT5. We hypothesize that delivery of JAGGED1 and induction of its downstream NOTCH non-canonical signaling in pediatric human osteoblasts constitutes an effective bone regenerative treatment. Delivering pediatric human bone-derived osteoblast-like cells to an in vivo murine bone loss model of a critically sized cranial defect, we identified that JAGGED1 promotes human pediatric osteoblast commitment and bone formation through p70 S6K phosphorylation. This approach highlights the potential of JAGGED1 and its downstream activators as innovative treatments for pediatric CF bone loss.
Samuel Antwi-Baffour, Benjamin Tetteh Mensah, Simon Aglona Ahiakonu
et al.
Abstract Background Malaria is a life-threatening parasitic disease typically transmitted through the bite of an infected Anopheles mosquito. There is ample evidence showing the potential of malaria infection to affect the counts of lymphocyte subpopulations in the peripheral blood, but the extent of alteration might not be consistent in all geographical locations, due to several local factors. Although Ghana is among the malaria-endemic countries, there is currently no available data on the level of alterations that occur in the counts of lymphocyte subpopulations during P. falciparum malaria infection among adults. Aim The study was to determine the immunophenotypic alterations in the level of peripheral blood lymphocytes and their subsets in adults with uncomplicated P. falciparum malaria infection and apparently healthy participants. Methods The study was a cross-sectional comparative study conducted in two municipalities of the Volta region of Ghana. Blood samples were collected from study participants and taken through serology (P. falciparum/Pan Rapid Diagnostic Kits), microscopy (Thick and thin blood films) and Haematological (Flow cytometric and Full blood count) analysis. Results A total of 414 participants, comprising 214 patients with malaria and 200 apparently healthy individuals (controls) were recruited into this study. Parasite density of the malaria patients ranged from 75/µL to 84,364/µL, with a mean of 3,520/µL. It was also observed that the total lymphocytes slightly decreased in the P. falciparum-infected individuals (Mean ± SD: 2.08 ± 4.93 × 109/L) compared to the control group (Mean ± SD: 2.47 ± 0.80 × 109/L). Again, there was a significant moderate positive correlation between parasite density and haematocrit levels (r = 0.321, p < 0.001). Apart from CD45 + T-cells, more people in the control group had normal values for the lymphocyte subsets measured compared to the malaria patients. Conclusions From the results obtained, there was high parasite density among the malaria patients suggestive of high intensity of infection in the case group. The malaria patients again showed considerable haematological alterations in lymphocyte sub-sets and the parasite density appeared to be strongly associated with CD4 + T-cell reduction. Also, the parasite density significantly associated with decreasing haematocrit levels. This indicates that lymphocyte subset enumeration can be used to effectively support malaria diagnosis.
Changyu Zhu, Yadira M Soto-Feliciano, John P Morris
et al.
Mutations in genes encoding components of chromatin modifying and remodeling complexes are among the most frequently observed somatic events in human cancers. For example, missense and nonsense mutations targeting the mixed lineage leukemia family member 3 (MLL3, encoded by KMT2C) histone methyltransferase occur in a range of solid tumors, and heterozygous deletions encompassing KMT2C occur in a subset of aggressive leukemias. Although MLL3 loss can promote tumorigenesis in mice, the molecular targets and biological processes by which MLL3 suppresses tumorigenesis remain poorly characterized. Here, we combined genetic, epigenomic, and animal modeling approaches to demonstrate that one of the mechanisms by which MLL3 links chromatin remodeling to tumor suppression is by co-activating the Cdkn2a tumor suppressor locus. Disruption of Kmt2c cooperates with Myc overexpression in the development of murine hepatocellular carcinoma (HCC), in which MLL3 binding to the Cdkn2a locus is blunted, resulting in reduced H3K4 methylation and low expression levels of the locus-encoded tumor suppressors p16/Ink4a and p19/Arf. Conversely, elevated KMT2C expression increases its binding to the CDKN2A locus and co-activates gene transcription. Endogenous Kmt2c restoration reverses these chromatin and transcriptional effects and triggers Ink4a/Arf-dependent apoptosis. Underscoring the human relevance of this epistasis, we found that genomic alterations in KMT2C and CDKN2A were associated with similar transcriptional profiles in human HCC samples. These results collectively point to a new mechanism for disrupting CDKN2A activity during cancer development and, in doing so, link MLL3 to an established tumor suppressor network.
Sara Popham, Maximilien Burq, Erin E Rainaldi
et al.
BackgroundMeasuring the amount of physical activity and its patterns using wearable sensor technology in real-world settings can provide critical insights into health status.
ObjectiveThis study’s aim was to develop and evaluate the analytical validity and transdemographic generalizability of an algorithm that classifies binary ambulatory status (yes or no) on the accelerometer signal from wrist-worn biometric monitoring technology.
MethodsBiometric monitoring technology algorithm validation traditionally relies on large numbers of self-reported labels or on periods of high-resolution monitoring with reference devices. We used both methods on data collected from 2 distinct studies for algorithm training and testing, one with precise ground-truth labels from a reference device (n=75) and the second with participant-reported ground-truth labels from a more diverse, larger sample (n=1691); in total, we collected data from 16.7 million 10-second epochs. We trained a neural network on a combined data set and measured performance in multiple held-out testing data sets, overall and in demographically stratified subgroups.
ResultsThe algorithm was accurate at classifying ambulatory status in 10-second epochs (area under the curve 0.938; 95% CI 0.921-0.958) and on daily aggregate metrics (daily mean absolute percentage error 18%; 95% CI 15%-20%) without significant performance differences across subgroups.
ConclusionsOur algorithm can accurately classify ambulatory status with a wrist-worn device in real-world settings with generalizability across demographic subgroups. The validated algorithm can effectively quantify users’ walking activity and help researchers gain insights on users’ health status.
Samuel C. Ugbaja, Sphamandla E. Mtambo, Aganze G. Mushebenge
et al.
The use of vaccinations and antiviral medications have gained popularity in the therapeutic management of avian influenza H7N9 virus lately. Antiviral medicines are more popular due to being readily available. The presence of the neuraminidase protein in the avian influenza H7N9 virus and its critical role in the cleavage of sialic acid have made it a target drug in the development of influenza virus drugs. Generally, the neuraminidase proteins have common conserved amino acid residues and any mutation that occurs around or within these conserved residues affects the susceptibility and replicability of the influenza H7N9 virus. Herein, we investigated the interatomic and intermolecular dynamic impacts of the experimentally reported E119V mutation on the oseltamivir resistance of the influenza H7N9 virus. We extensively employed molecular dynamic (MD) simulations and subsequent post-MD analyses to investigate the binding mechanisms of oseltamivir-neuraminidase wildtype and E119V mutant complexes. The results revealed that the oseltamivir-wildtype complex was more thermodynamically stable than the oseltamivir-E119V mutant complex. Oseltamivir exhibited a greater binding affinity for wildtype (−15.46 ± 0.23 kcal/mol) relative to the E119V mutant (−11.72 ± 0.21 kcal/mol). The decrease in binding affinity (−3.74 kcal/mol) was consistent with RMSD, RMSF, SASA, PCA, and hydrogen bonding profiles, confirming that the E119V mutation conferred lower conformational stability and weaker protein–ligand interactions. The findings of this oseltamivir-E119V mutation may further assist in the design of compounds to overcome E119V mutation in the treatment of influenza H7N9 virus patients.