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Nevin Manimala Statistics

Molecular characterization of hypermucoviscous carbapenemase-encoding Klebsiella pneumoniae isolates from an Egyptian hospital

Ann N Y Acad Sci. 2024 Apr 5. doi: 10.1111/nyas.15126. Online ahead of print.

ABSTRACT

This study aimed to screen antibiotic resistance and virulence genes in carbapenem-resistant hypermucoviscous Klebsiella pneumoniae isolates from an Egyptian hospital. Among 38 previously confirmed carbapenem-nonsusceptible K. pneumoniae isolates, a string test identified three isolates as positive for hypermucoviscosity. Phenotypic characterization and molecular detection of carbapenemase- and virulence-encoding genes were performed. PCR-based multilocus sequence typing and phylogenetics were used to determine the clonality and global epidemiology of the strains. The coexistence of virulence and resistance genes in the isolates was analyzed statistically using a chi-square test. Three isolates showed the presence of carbapenemase-encoding genes (blaNDM, blaVIM, and blaIMP), adhesion genes (fim-H-1 and mrkD), and siderophore genes (entB); the isolates belonged to sequence types (STs) 101, 1310, and 1626. The relatedness between these sequence types and the sequence types of globally detected hypermucoviscous K. pneumoniae that also harbor carbapenemases was determined. Our analysis showed that the resistance and virulence profiles were not homogenous. Phylogenetically, different clones clustered together. There was no significant association between the presence of resistance and virulence genes in the isolates. There is a need for periodic surveillance of the healthcare settings in Egypt and globally to understand the true epidemiology of carbapenem-resistant, hypermucoviscous K. pneumoniae.

PMID:38577761 | DOI:10.1111/nyas.15126

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A crossover study to evaluate the pharmacokinetics and bioequivalence of hydroxychloroquine tablets in healthy Chinese subjects

Int J Clin Pharmacol Ther. 2024 Apr 5. doi: 10.5414/CP204406. Online ahead of print.

ABSTRACT

AIMS: Hydroxychloroquine (HCQ) has a high variability and a long half-life in the human body. The purpose of this study was to evaluate the bioequivalence of a generic HCQ tablet (test preparation) versus a brand HCQ tablet (reference preparation) under fasting and fed conditions in a crossover design.

MATERIALS AND METHODS: This was an open-label, two-period randomized, single-dose, crossover study in 47 healthy Chinese subjects who were sequentially and randomly allocated either to the fed group (high-fat meal; n = 23) or the fasting group (n = 24). Participants in each group were randomized to the two arms to receive either a single 200-mg dose of the test preparation or a 200-mg dose of the reference preparation. The application of the two preparations in each patient was separated by a 28-day washout period, regarded as sufficiently long to avoid significant interference from residual drug in the body. Whole blood samples were collected over 72 hours after drug administration.

RESULTS: A total of 23 subjects completed both the fed and the fasting parts of the trial. There were no significant differences in Cmax, AUC0-72h, and T1/2 between the test and reference preparation (p > 0.05). Food had no significant effect on Cmax and T1/2 (p > 0.05), but AUC0-72h values were significantly reduced under fed condition compared to fasting condition (p < 0.05). The 90% confidence intervals (CIs) for the geometric mean ratios (GMRs) of Cmax and AUC0-72h were 0.84 – 1.05 and 0.89 – 0.98 in the fed study, and 0.97 – 1.07 and 0.97 – 1.05 in the fasting study, respectively. The carryover effect due to non-zero blood concentrations resulted in higher AUC0-72h values in the second period for both test and reference formulations and had no effect on the statistical results. No serious adverse events were reported.

CONCLUSION: The investigation demonstrated that the test and reference preparations are bioequivalent and well tolerated under both fasting and fed conditions in healthy Chinese subjects.

PMID:38577751 | DOI:10.5414/CP204406

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Clinical Assessment of Magnetic Resonance Spectroscopy and Diffusion-Weighted Imaging in Diffuse Glioma: Insights Into Histological Grading and IDH Classification

Can Assoc Radiol J. 2024 Apr 5:8465371241238917. doi: 10.1177/08465371241238917. Online ahead of print.

ABSTRACT

PURPOSE: To assess the diagnostic utility of clinical magnetic resonance spectroscopy (MRS) and diffusion-weighted imaging (DWI) in distinguishing between histological grading and isocitrate dehydrogenase (IDH) classification in adult diffuse gliomas.

METHODS: A retrospective analysis was conducted on 247 patients diagnosed with adult diffuse glioma. Experienced radiologists evaluated DWI and MRS images. The Kruskal-Wallis test examined differences in DWI and MRS-related parameters across histological grades, while the Mann-Whitney U test assessed molecular classification. Receiver Operating Characteristic (ROC) curves evaluated parameter effectiveness. Survival curves, stratified by histological grade and IDH classification, were constructed using the Kaplan-Meier test.

RESULTS: The cohort comprised 141 males and 106 females, with ages ranging from 19 to 85 years. The Kruskal-Wallis test revealed significant differences in ADC mean, Cho/NAA, and Cho/Cr concerning glioma histological grade (P < .01). Subsequent application of Dunn’s test showed significant differences in ADC mean among each histological grade (P < .01). Notably, Cho/NAA exhibited a marked distinction between grade 2 and grade 3/4 gliomas (P < .01). The Mann-Whitney U test indicated that only ADC mean showed statistical significance for IDH molecular classification (P < .01). ROC curves were constructed to demonstrate the effectiveness of the specified parameters. Survival curves were also delineated to portray survival outcomes categorized by histological grade and IDH classification. Conclusions: Clinical MRS demonstrates efficacy in glioma histological grading but faces challenges in IDH classification. Clinical DWI’s ADC mean parameter shows significant distinctions in both histological grade and IDH classification.

PMID:38577746 | DOI:10.1177/08465371241238917

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Measurement of the major ignored burden of multiple myeloma, pernicious anaemia and of other haematological conditions on partners and family members: A cross-sectional study

Eur J Haematol. 2024 Apr 5. doi: 10.1111/ejh.14206. Online ahead of print.

ABSTRACT

BACKGROUND: Having a haematological condition can adversely affect the quality of life (QoL) of family members/partners of patients. It is important to measure this often ignored burden in order to implement appropriate supportive interventions.

OBJECTIVE: To measure current impact of haematological conditions on the QoL of family members/partners of patients, using the Family Reported Outcome Measure-16 (FROM-16).

METHODS: A cross-sectional study, recruited online through patient support groups, involved UK family members/partners of people with haematological conditions completing the FROM-16.

RESULTS: 183 family members/partners (mean age = 60.5 years, SD = 13.2; females = 62.8%) of patients (mean age = 64.1, SD = 12.8; females = 46.4%) with 12 haematological conditions completed the FROM-16. The FROM-16 mean total score was 14.0 (SD = 7.2), meaning ‘a moderate effect on QoL’. The mean FROM-16 scores of family members of people with multiple myeloma (mean = 15.8, SD = 6.3, n = 99) and other haematological malignancies (mean = 13.9, SD = 7.8, n = 29) were higher than of people with pernicious anaemia (mean = 10.7, SD = 7.5, n = 47) and other non-malignant conditions (mean = 11, SD = 7.4, n = 56, p < .01). Over one third (36.1%, n = 183) of family members experienced a ‘very large effect’ (FROM-16 score>16) on their quality of life.

CONCLUSIONS: Haematological conditions, in particular those of malignant type, impact the QoL of family members/partners of patients. Healthcare professionals can now, using FROM-16, identify those most affected and should consider how to provide appropriate holistic support within routine practice.

PMID:38577720 | DOI:10.1111/ejh.14206

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Evaluating the effectiveness of artificial intelligence-based tools in detecting and understanding sleep health misinformation: Comparative analysis using Google Bard and OpenAI ChatGPT-4

J Sleep Res. 2024 Apr 5:e14210. doi: 10.1111/jsr.14210. Online ahead of print.

ABSTRACT

This study evaluates the performance of two major artificial intelligence-based tools (ChatGPT-4 and Google Bard) in debunking sleep-related myths. More in detail, the present research assessed 20 sleep misconceptions using a 5-point Likert scale for falseness and public health significance, comparing responses of artificial intelligence tools with expert opinions. The results indicated that Google Bard correctly identified 19 out of 20 statements as false (95.0% accuracy), not differing from ChatGPT-4 (85.0% accuracy, Fisher’s exact test p = 0.615). Google Bard’s ratings of the falseness of the sleep misconceptions averaged 4.25 ± 0.70, showing a moderately negative skewness (-0.42) and kurtosis (-0.83), and suggesting a distribution with fewer extreme values compared with ChatGPT-4. In assessing public health significance, Google Bard’s mean score was 2.4 ± 0.80, with skewness and kurtosis of 0.36 and -0.07, respectively, indicating a more normal distribution compared with ChatGPT-4. The inter-rater agreement between Google Bard and sleep experts had an intra-class correlation coefficient of 0.58 for falseness and 0.69 for public health significance, showing moderate alignment (p = 0.065 and p = 0.014, respectively). Text-mining analysis revealed Google Bard’s focus on practical advice, while ChatGPT-4 concentrated on theoretical aspects of sleep. The readability analysis suggested Google Bard’s responses were more accessible, aligning with 8th-grade level material, versus ChatGPT-4’s 12th-grade level complexity. The study demonstrates the potential of artificial intelligence in public health education, especially in sleep health, and underscores the importance of accurate, reliable artificial intelligence-generated information, calling for further collaboration between artificial intelligence developers, sleep health professionals and educators to enhance the effectiveness of sleep health promotion.

PMID:38577714 | DOI:10.1111/jsr.14210

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Unique immunohistochemical profiles of MUC5AC, MUC6, P53, and Ki67 in gastric atypical hyperplasia and dysplasia

Int J Clin Exp Pathol. 2024 Mar 15;17(3):63-71. doi: 10.62347/JVIX8887. eCollection 2024.

ABSTRACT

OBJECTIVES: Differentiating gastric atypical hyperplasia (AH) from dysplasia, including low-grade dysplasia (LGD) and high-grade dysplasia (HGD), poses significant challenges in small biopsies and specimens with technical artifacts. This study aims to establish objective diagnostic criteria for these conditions through combined morphologic and immunohistochemical (IHC) analyses.

METHODS: Between January 2018 and September 2020, a total of 123 gastric mucosa biopsy specimens were collected at Anyang Tumor Hospital. According to the WHO Classification of Digestive System Tumors (5th edition), specimens were categorized into three groups: AH (n=48), LGD (n=30), and HGD (n=45). Morphologic characteristics were assessed, and IHC staining for MUC5AC, MUC6, MUC2, CD10, P53, and Ki67 was performed, followed by statistical analysis.

RESULTS: Histologically, AH was predominantly marked by a pronounced inflammatory background (60.42%), intestinal metaplasia (64.58%), indistinct boundaries (83.33%), and a distinct maturation gradient (97.72%). AH nuclei were typically circular (97.92%), with a high nucleus-to-cytoplasm ratio (64.58%), prominent nucleoli (47.92%), and preserved polarity (89.58%). In contrast, LGD and HGD typically exhibited well-defined boundaries with an absent maturation gradient. LGD nuclei were rod-shaped (96.67%), with a low nucleus-to-cytoplasm ratio (96.67%) and preserved polarity (100%), whereas HGD demonstrated a loss of cellular polarity (77.78%). IHC findings revealed a consistent maturation gradient in AH, with polarized MUC5AC and MUC6 expression, significantly reduced in LGD (86.67%), and absent in HGD. P53 expression in HGD showed a predominant ‘mutation-type pattern’ (66.67%), contrasting with ‘wild-type pattern’ expression in AH and LGD (100%, 93.33%). Ki67 expression patterns varied from a ‘pit neck pattern’ in AH (95.83%) to a ‘polarity pattern’ in LGD (76.67%) and a ‘diffuse pattern’ in HGD (57.78%). The expression patterns of MUC5AC, MUC6, CD10, P53, and Ki67 varied significantly across the three groups (P<0.001).

CONCLUSIONS: The integration of histomorphological features and expression profiles of MUC5AC, MUC6, P53, and Ki67 is instrumental in diagnosing gastric atypical hyperplasia and dysplasia.

PMID:38577693 | PMC:PMC10988094 | DOI:10.62347/JVIX8887

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Vitamin D [Serum 25(OH) cholecalciferol] Insufficiency is Associated With Childhood Asthma: Recent Case-Control Findings From Bangladesh

Glob Pediatr Health. 2024 Apr 3;11:2333794X241240574. doi: 10.1177/2333794X241240574. eCollection 2024.

ABSTRACT

Objectives. To evaluate the interaction between childhood asthma and S. 25(OH) cholecalciferol among Bangladeshi children. Methods. This case control study was conducted in child asthma clinic, Bangladesh Shishu Hospital Institute during March-August 2021. Comparison was made between clinically-diagnosed (following GINA guideline) asthmatic children (2-12 years-old) (cases = 87) and age and sex-matched children having no respiratory illness (controls = 90) using SPSS’ (Statistical Package for Social Science, V.23.0 Windows) software. Results. Serum 25(OH) cholecalciferol was found to be significantly lower among the cases than the controls (P < .01). The cases had 3.4 times higher likelihood of having low vitamin D (combined deficient + insufficient) than the controls (P < .01). Conclusions. The results of the study demonstrate an association of Serum 25 (OH) cholecalciferol with asthma which underscores the importance of potential future trial to evaluate the efficacy of Vitamin-D supplementation for understanding the outcomes of asthmatic Bangladeshi children.

PMID:38577660 | PMC:PMC10993668 | DOI:10.1177/2333794X241240574

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The Impact of SARS-CoV-2 Infection on the Length of Stay in the Neuro-ICU:A Prospective Multicenter Cohort Study in Eight Neuro-ICU, China Between February and April 2023

Neuropsychiatr Dis Treat. 2024 Mar 30;20:765-775. doi: 10.2147/NDT.S447887. eCollection 2024.

ABSTRACT

PURPOSE: The SARS-CoV-2 infection cases are increasing rapidly in neuro-intensive care units (neuro-ICUs) at the beginning of 2023 in China. We aimed to characterize the prevalence, risk factors, and prognosis of critically ill patients treated in neuro-ICUs.

MATERIALS AND METHODS: In the prospective, multicenter, observational registry study, critically ill patients with intracerebral hemorrhage (ICH), subarachnoid hemorrhage (SAH), and traumatic brain injury (TBI) admitted to eight Chinese neuro-ICUs between Feb 16, 2023, to Apr 30, 2023 were enrolled for the study. Mortality and ICU stay day were used as the primary outcomes.

RESULTS: 131 patients were finally included and analyzed (mean age 60.36 years [SD 13.81], 64.12% male, 39.69% SARS-CoV-2 infected). The mortality is higher in the SARS-CoV-2 infection group without statistical signification (7.69% vs 5.06%, p>0.05). The length of stay (LOS) in neuro-ICUs was significantly longer among the SARS-CoV-2 infection patients (7(1-12) vs 4(1-8), p<0.01), with increased viral pneumonia occurrence (58.54% vs 7.32%, p<0.01). SARS-CoV-2 infection, surgery, and low GCS scores were independent risk factors for prolonged LOS, and respiratory/renal failure were independent risk factors for death.

CONCLUSION: Based on the present neuro-ICU cohort, SARS-CoV-2 infection was a significant risk for the prolonged LOS of neuro-critically ill patients.

TRIAL REGISTRATION: Registered with Chictr.org.cn (ChiCTR2300068355) at 16 February 2023, Prospective registration. https://www.chictr.org.cn/showproj.html?proj=188252.

PMID:38577632 | PMC:PMC10992672 | DOI:10.2147/NDT.S447887

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Prognostic significance of BRCA1 and BRCA2 methylation status in circulating cell-free DNA of Pancreatic Cancer patients

J Cancer. 2024 Mar 11;15(9):2573-2579. doi: 10.7150/jca.93184. eCollection 2024.

ABSTRACT

Introduction: Pancreatic cancer is the most fatal cancer type in the world. Its high mortality is mostly correlated to the absence of symptoms and the difficulty in early diagnosis, which in the majority of the cases occurs when the disease has already spread metastasis. Nowadays, tests that could predict early diagnosis are not available yet and the number of prognostic tests is limited. Hence, there is an urgent need for biomarkers capable of detecting early development or the rapid progression of the disease. Patients and Methods: DNA methylation represents the most frequent epigenetic event among tumor suppressor genes that are involved in various carcinogenic pathways. In the recent study we have tried to evaluate, for the first time, the prognostic value of BRCA1 and BRCA2 methylation in the cell-free DNA of pancreatic cancer patients. Using methylation-specific real-time PCR we examined the methylation status of BRCA1 and BRCA2 in 55 patients with operable and 50 patients with metastatic pancreatic cancer. In the operable disease setting, BRCA1 was found to be methylated in 33/55 (63.5%) patients examined while BRCA2 was also highly methylated in 31/55 (56.3%). In the metastatic disease, BRCA1 was found to be methylated in 26/50 (52%) while BRCA2 was found methylated in 23/50 (46%). Results: All control samples were negative for BRCA1 orBRCA2 promoter methylation. Patients with operable pancreatic cancer and a methylated BRCA1 and BRCA2 promoter status had a statistically significant poorer outcome as compared with patients with a non-methylated one (p=0.012 and p=0.001, respectively). Conclusion: In this study plasma methylation of BRCA1 and BRCA2 represents a frequent event in both the operable as well as in the metastatic setting. BRCA1 and BRCA2 methylation was significant and correlated with decreased survival in patients with operable pancreatic cancer. A larger cohort of patients is required to further explore the potential of these findings as well as to investigate whether BRCA1/2 methylation in plasma could serve as a potential prognostic biomarker in pancreatic cancer.

PMID:38577595 | PMC:PMC10988318 | DOI:10.7150/jca.93184

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Data to knowledge in action: A longitudinal analysis of GenBank metadata

Proc Assoc Inf Sci Technol. 2020;57(1):e253. doi: 10.1002/pra2.253. Epub 2020 Oct 22.

ABSTRACT

Studies typically use publication-based authorship data to study the relationships between collaboration networks and knowledge diffusion. However, collaboration in research often starts long before publication with data production efforts. In this project we ask how collaboration in data production networks affects and contributes to knowledge diffusion, as represented by patents, another form of knowledge diffusion. We drew our data from the metadata associated with genetic sequence records stored in the National Institutes of Health’s GenBank database. After constructing networks for each year and aggregating summary statistics, regressions were used to test several hypotheses. Key among our findings is that data production team size is positively related to the number of patents each year. Also, when actors on average have more links, we tend to see more patents. Our study contributes in the area of science of science by highlighting the important role of data production in the diffusion of knowledge as measured by patents.

PMID:38577577 | PMC:PMC10993725 | DOI:10.1002/pra2.253