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Biochemical Genetics Jul 2024Iron loading is regarded as the primary cause of endocrine abnormalities in thalassemia major patients. Thus, the purpose of the current research was to explore the...
Iron loading is regarded as the primary cause of endocrine abnormalities in thalassemia major patients. Thus, the purpose of the current research was to explore the impact of thalassemia genotypes, hepcidin antimicrobial peptide (HAMP) and hereditary hemochromatosis (HFE) gene variants, and hepcidin expression on serum ferritin and endocrinal complications in thalassemia patients. The study comprised fifty beta-thalassemia cases and fifty age- and sex-matched controls. Genotyping of the Beta-globin gene (HBB), HAMP, and exon 2 of the HFE gene was performed using Sanger sequencing. C282Y (c.845G > A) variant of the HFE gene was determined by PCR-RFLP. Hepcidin mRNA expression was assessed by qRT-PCR. Biochemical and hormonal studies were done for all patients. Hypogonadism and short stature were found in 56% and 20% of the investigated cases, respectively. Molecular studies reported a statistically higher frequency of the HAMP variant c.-582A > G in thalassemic patients than controls. Significant downregulation of hepcidin expression was found in cases compared to healthy subjects that was significantly associated with short stature. Considering the thalassemia alleles, the IVSI.1G > A (β) allele was statistically related to hypogonadism. Our results proposed that thalassemia genotypes and downregulated hepcidin expression were the potential risk factors for endocrinopathies in our cases. We also demonstrated an increased incidence of the HAMP promoter variant c.- 582A > G that might have a role in the pathogenesis of iron overload in thalassemic cases. Significant downregulation of hepcidin expression, that contributes to increased iron burden, could be used as a future therapeutic target in these patients.
PubMed: 38954212
DOI: 10.1007/s10528-024-10868-5 -
Methods in Molecular Biology (Clifton,... 2024A given protein can perform numerous roles in a cell with its participation in protein complexes and distinct localization within the cell playing a critical role in its...
A given protein can perform numerous roles in a cell with its participation in protein complexes and distinct localization within the cell playing a critical role in its diverse functions. Thus, the ability to artificially dimerize proteins and recruit proteins to specific locations in a cell has become a powerful tool for the investigation of protein function and the understanding of cell biology. Here, we discuss two systems that have been used to activate signal transduction pathways, a chemically inducible dimerization (CID) and a light-inducible (LI) system to control signaling and cytoskeletal regulation in a spatial and temporal manner.
Topics: Optogenetics; Signal Transduction; Protein Multimerization; Humans; Animals; Light; Protein Transport
PubMed: 38954201
DOI: 10.1007/978-1-0716-3894-1_8 -
Japanese Journal of Radiology Jul 2024Large language models (LLMs) are rapidly advancing and demonstrating high performance in understanding textual information, suggesting potential applications in...
PURPOSE
Large language models (LLMs) are rapidly advancing and demonstrating high performance in understanding textual information, suggesting potential applications in interpreting patient histories and documented imaging findings. As LLMs continue to improve, their diagnostic abilities are expected to be enhanced further. However, there is a lack of comprehensive comparisons between LLMs from different manufacturers. In this study, we aimed to test the diagnostic performance of the three latest major LLMs (GPT-4o, Claude 3 Opus, and Gemini 1.5 Pro) using Radiology Diagnosis Please Cases, a monthly diagnostic quiz series for radiology experts.
MATERIALS AND METHODS
Clinical history and imaging findings, provided textually by the case submitters, were extracted from 324 quiz questions originating from Radiology Diagnosis Please cases published between 1998 and 2023. The top three differential diagnoses were generated by GPT-4o, Claude 3 Opus, and Gemini 1.5 Pro, using their respective application programming interfaces. A comparative analysis of diagnostic performance among these three LLMs was conducted using Cochrane's Q and post hoc McNemar's tests.
RESULTS
The respective diagnostic accuracies of GPT-4o, Claude 3 Opus, and Gemini 1.5 Pro for primary diagnosis were 41.0%, 54.0%, and 33.9%, which further improved to 49.4%, 62.0%, and 41.0%, when considering the accuracy of any of the top three differential diagnoses. Significant differences in the diagnostic performance were observed among all pairs of models.
CONCLUSION
Claude 3 Opus outperformed GPT-4o and Gemini 1.5 Pro in solving radiology quiz cases. These models appear capable of assisting radiologists when supplied with accurate evaluations and worded descriptions of imaging findings.
PubMed: 38954192
DOI: 10.1007/s11604-024-01619-y -
Drugs - Real World Outcomes Jul 2024Protein convertase subtilisin/kexin type 9 inhibitors (PCSK9i) are novel lipid-lowering agents used in patients with cardiovascular disease. Despite reassuring safety...
AIMS
Protein convertase subtilisin/kexin type 9 inhibitors (PCSK9i) are novel lipid-lowering agents used in patients with cardiovascular disease. Despite reassuring safety data from pivotal trials, increasing evidence from real-world studies suggests that PCSK9i increase the risk of bacterial and viral infections. Therefore, this study aimed to identify signals of infection-related adverse events (AEs) associated with PCSK9i.
METHODS
We performed an observational pharmacovigilance study using the World Health Organization's VigiBase, recorded up to December 2022. We included individual case safety reports (ICSRs) of PCSK9 inhibitors, alirocumab and evolocumab, and compared them with those of other drugs. Infection-related ICSRs were retrieved from the Medical Dictionary for Regulatory Activities System Organ Class 'infections and infestations.'
RESULTS
Among 114,293 reports (258,099 drug-AE pairs) related to PCSK9 inhibitors, 54% included female patients, 41% included patients aged ≥65 years, and 82% included patients who received evolocumab. Additionally, beyond AEs recognized by regulatory authorities, organ infections such as influenza (reporting odds ratio [ROR] 2.89, 95% confidence interval [CI] 2.74-3.05), gastric infections (ROR 2.47, 95% CI 1.63-3.75), and kidney infections (ROR 1.36, 95% CI 1.06-1.73) were observed. Sensitivity analysis indicated a heightened risk of infection-related AEs associated with PCSK9i regardless of the specific drug type.
CONCLUSIONS
In addition to the labelled respiratory infections, six infection-related symptoms in the gastrointestinal, urinary, and renal organs were identified. Our findings support the need for systematic surveillance of infections among PCSK9i users.
PubMed: 38954190
DOI: 10.1007/s40801-024-00430-5 -
Journal of Gastrointestinal Cancer Jul 2024Treatment of retroperitoneal lymph node metastases (RPN) from colon cancer (CC) is a therapeutic challenge. Available evidence supporting a curative approach is weak and...
PURPOSE
Treatment of retroperitoneal lymph node metastases (RPN) from colon cancer (CC) is a therapeutic challenge. Available evidence supporting a curative approach is weak and uncertainties remain concerning the extent of the dissection, the optimal timing for surgery, and the role of adjuvant radiotherapy. We report the outcomes of a curative intent strategy in a recent monocentric series of patients.
METHODS
We did a retrospective review of all curative intent surgical treatment of RPN from CC performed consecutively in a French university hospital from June 2015 to April 2021. Demographics, clinicopathological, and molecular characteristics were evaluated. We describe recurrence-free and overall survival and factors related to recurrence.
RESULTS
Records from 18 patients were reviewed. The median age was 69 years. Most of the patients were male (55%), ASA 1-2 (94%), had a left-sided primary colon cancer (73%), and had metachronous RPN (62%). Thirteen patients (72%) experienced recurrence. Recurrence was often limited to RPN (27%) or liver (22%). Four patients underwent a second surgery for RPN recurrence. Median disease-free and overall survival were 22 months and 50 months after RPN surgery. We did not find any factor associated with recurrence. Short-term recurrence (< 6 months) was associated with shorter overall survival (0.031).
CONCLUSION
The current results suggest that RPN resection is feasible and associated with long survival in selected patients. Further studies evaluating the benefit of curative strategies including radical surgery for patients with potentially resectable RPN are warranted.
PubMed: 38954189
DOI: 10.1007/s12029-024-01086-8 -
Fish Physiology and Biochemistry Jul 2024The wild Onychostoma macrolepis, a species under national class II protection in China, lacks a specific compound feed for captive rearing. Understanding the dietary...
The wild Onychostoma macrolepis, a species under national class II protection in China, lacks a specific compound feed for captive rearing. Understanding the dietary amino acid pattern is crucial for optimal feed formulation. This study aimed to investigate the effects of the four different dietary amino acid patterns, i.e., anchovy fishmeal protein (FMP, control group) and muscle protein (MP), whole-body protein (WBP), fish egg protein (FEP) of juvenile Onychostoma macrolepis, on the growth performance, body composition, intestinal morphology, enzyme activities, and the expression levels of gh, igf, mtor genes in juveniles. In a 12-week feeding trial with 240 juveniles (3.46±0.04g), the MP group demonstrated superior outcomes in growth performance (FBW, WGR, SGR), feed utilization efficiency (PER, PRE, FCR). Notably, it exhibited higher crude protein content in whole-body fish, enhanced amino acid composition in the liver, and favorable fatty acid health indices (AI, TI, h/H) in muscle compared to other groups (P < 0.05). Morphologically, the MP and FMP groups exhibited healthy features. Additionally, the MP group displayed significantly higher activities of TPS, ALP, and SOD, along with elevated expression levels of gh, igf, mtor genes, distinguishing it from the other groups (P < 0.05). This study illustrated that the amino acid pattern of MP emerged as a suitable dietary amino acid pattern for juvenile Onychostoma macrolepis. Furthermore, the findings provide valuable insights for formulating effective feeds in conserving and sustainably farming protected species, enhancing the research's broader ecological and aquacultural significance.
PubMed: 38954179
DOI: 10.1007/s10695-024-01372-z -
Analytical Sciences : the International... Jul 2024This study introduces a suite of robust models aimed to advance the determination of physiochemical properties in heavy oil refinery fractions. By integrating real-time...
This study introduces a suite of robust models aimed to advance the determination of physiochemical properties in heavy oil refinery fractions. By integrating real-time analytical technique inside the refinery analysis, we have developed a single analyzer capable of employing six partial least square regression equations. These designed models enable to provide real-time prediction of critical petroleum properties, such as sulfur content, micro carbon residues (MCR), asphaltene content, heating value, and the concentrations of nickel and vanadium metals. Specifically tailored for heavy oil in refinery feeds with an American petroleum institute (API) gravity range of 3° to 32° and sulfur content of 2.8 to 5.5 wt%, the models streamline the analysis process within refinery operations, bridging the gap between catalytic and non-catalytic processes across refinery units. The accuracy of our physiochemical prediction models has been validated against American Society for Testing and Materials (ASTM) standards, demonstrating their capability to deliver precise real-time property values. This approach not only enhances the efficiency of refinery analysis but also sets a new standard for the monitoring and optimization of heavy oil processing in real-time approach.
PubMed: 38954177
DOI: 10.1007/s44211-024-00625-4 -
Gastric Cancer : Official Journal of... Jul 2024Accurate prediction of pathologic results for early gastric cancer (EGC) based on endoscopic findings is essential in deciding between endoscopic and surgical resection....
BACKGROUND
Accurate prediction of pathologic results for early gastric cancer (EGC) based on endoscopic findings is essential in deciding between endoscopic and surgical resection. This study aimed to develop an artificial intelligence (AI) model to assess comprehensive pathologic characteristics of EGC using white-light endoscopic images and videos.
METHODS
To train the model, we retrospectively collected 4,336 images and prospectively included 153 videos from patients with EGC who underwent endoscopic or surgical resection. The performance of the model was tested and compared to that of 16 endoscopists (nine experts and seven novices) using a mutually exclusive set of 260 images and 10 videos. Finally, we conducted external validation using 436 images and 89 videos from another institution.
RESULTS
After training, the model achieved predictive accuracies of 89.7% for undifferentiated histology, 88.0% for submucosal invasion, 87.9% for lymphovascular invasion (LVI), and 92.7% for lymph node metastasis (LNM), using endoscopic videos. The area under the curve values of the model were 0.992 for undifferentiated histology, 0.902 for submucosal invasion, 0.706 for LVI, and 0.680 for LNM in the test. In addition, the model showed significantly higher accuracy than the experts in predicting undifferentiated histology (92.7% vs. 71.6%), submucosal invasion (87.3% vs. 72.6%), and LNM (87.7% vs. 72.3%). The external validation showed accuracies of 75.6% and 71.9% for undifferentiated histology and submucosal invasion, respectively.
CONCLUSIONS
AI may assist endoscopists with high predictive performance for differentiation status and invasion depth of EGC. Further research is needed to improve the detection of LVI and LNM.
PubMed: 38954175
DOI: 10.1007/s10120-024-01524-3 -
AIDS and Behavior Jul 2024Nearly 40% of people with HIV (PWH) experience HIV-associated Neurocognitive Disorder (HAND). In this 3-group efficacy study, 216 PWH 40 + years with HAND or...
A 2-Year Longitudinal Randomized Control Trial of Speed of Processing Cognitive Training in Aging Adults with HIV-Associated Neurocognitive Disorder: Results of the Think Fast Study.
Nearly 40% of people with HIV (PWH) experience HIV-associated Neurocognitive Disorder (HAND). In this 3-group efficacy study, 216 PWH 40 + years with HAND or borderline HAND were randomized to either: (1) 10 h of SOP training (n = 70); (2) 20 h of SOP training (n = 73), or (3) 10 h of Internet navigation training (n = 73; contact control group). Participants were administered a measure of SOP [i.e., the Useful Field of View Test (UFOV®)] at baseline, at posttest immediately after training, and at year 1 and year 2 follow up. Intent-to-treat linear mixed-effect models with subject-specific intercept and slope were fitted to estimate between-group mean differences at the follow-up time-points. At the post-intervention time-point, small beneficial SOP training effects were observed for the 10-h group in UFOV® total (d = 0.28, p = 0.002). Effects were of larger magnitude for the 20-h group in these same outcomes [UFOV® total (d = 0.43, p < 0.001)]. These results indicated better benefit with more training. No intervention effect was observed at year 1. At year 2, beneficial effects of small magnitude were observed again in the 10-h group [UFOV® total (d = 0.22, p = 0.253)] with larger small-to-moderate magnitude in the 20-h group [UFOV® total (d = 0.32, p = 0.104)]. This study suggests that SOP training can improve a key indicator of this cognitive performance and that treatment gains are small-to-moderate over a two-year period. Prior literature suggests slower SOP is predictive of impairment in everyday functioning in older PWH; such an approach could potentially improve everyday functioning in PWH.
PubMed: 38954173
DOI: 10.1007/s10461-024-04409-9 -
AAPS PharmSciTech Jul 2024The intranasal route has demonstrated superior systemic bioavailability due to its extensive surface area, the porous nature of the endothelial membrane, substantial...
The intranasal route has demonstrated superior systemic bioavailability due to its extensive surface area, the porous nature of the endothelial membrane, substantial blood flow, and circumvention of first-pass metabolism. In traditional medicinal practices, Bacopa monnieri, also known as Brahmi, is known for its benefits in enhancing cognitive functions and potential effects in epilepsy. This study aimed to develop and optimize a thermosensitive in-situ nasal gel for delivering Bacoside A, the principal active compound extracted from Bacopa monnieri. The formulation incorporated Poloxamer 407 as a thermogelling agent and HPMC K4M as the Mucoadhesive polymer. A 3-factorial design approach was employed for Optimization. Among the formulations. F7 exhibited the most efficient Ex-vivo permeation through the nasal mucosa, achieving 94.69 ± 2.54% permeation, and underwent a sol-gel transition at approximately 30.48 °C. The study's factorial design revealed that gelling temperature and mucoadhesive strength were critical factors influencing performance. The potential of in-situ nasal Gel (Optimized Batch-F7) for the treatment of epilepsy was demonstrated in an in-vivo investigation using a PTZ-induced convulsion model. This formulation decreased both the occurrence and intensity of seizures. The optimized formulation F7 showcases significant promise as an effective nasal delivery system for Bacoside A, offering enhanced bioavailability and potentially increased efficacy in epilepsy treatment.
PubMed: 38954171
DOI: 10.1208/s12249-024-02870-2