Tag: nevin manimala

Clin Cancer Res. 2024 Jul 26. doi: 10.1158/1078-0432.CCR-24-0461. Online ahead of print.

ABSTRACT

PURPOSE: To evaluate the efficacy and safety of nanvuranlat (a LAT1 inhibitor) monotherapy as a later-line treatment in advanced, metastatic, and refractory BTCs.

PATIENTS AND METHODS: The multicenter, randomized, double-blind, placebo-controlled, phase II study was conducted across 14 leading Japanese cancer centers and hospitals. Nanvuranlat 25 mg/m2/day or placebo was given intravenously in cycles of five consecutive days, followed by nine days off. The primary endpoint was progression-free survival (PFS). Secondary endpoints included overall survival (OS) and disease control rate (DCR). Subgroup analysis was performed in patients with high LAT1 expression and BTC-subtypes.

RESULTS: A total of 211 patients were screened, 105 eligible patients were randomized, and then 70 received nanvuranlat and 35 received placebo. Nanvuranlat demonstrated an improvement in PFS when compared to placebo (Hazard Ratio (HR) 0.56; 95% CI, 0.34 – 0.90; P = 0.02). Grade 3 or higher adverse events were reported in 30.0% and 22.9% of those in the nanvuranlat and placebo groups, respectively. The overall survival (OS) was not statistically different between nanvuranlat- and placebo-treated patients. An exploratory analysis indicated that nanvuranlat is warranted to evaluate its long-term clinical benefit in patients with intrahepatic cholangiocarcinoma, extrahepatic cholangiocarcinoma, and gallbladder cancer.

CONCLUSION: Compared with placebo, nanvuranlat improved PFS in patients with advanced and refractory BTC with an acceptable safety profile. Further studies of this promising compound are warranted in the population of patients who are exhausted from treatment options.

PMID:39058429 | DOI:10.1158/1078-0432.CCR-24-0461

Health Promot Int. 2024 Aug 1;39(4):daae083. doi: 10.1093/heapro/daae083.

ABSTRACT

The development of health literacy in China is relatively slow, and there are fewer health literacy scales, which is difficult to measure. Therefore, this study aims to promote the development of health literacy in China through the translation and application of the European Health Literacy Survey Questionnaire (HLS-EU-Q47). The scale was translated into Chinese, back-translated, culturally adapted and finally subjected to psychometric evaluation. A multi-stage stratified sampling method was used to select 2504 residents to test the reliability and validity of a questionnaire on health literacy. Exploratory factor analysis (EFA) and confirmatory factor analysis (CFA) were used to evaluate the validity of the results, and the back consistency was calculated by Cronbach’s alpha coefficient. The EFA revealed that health care, disease prevention and health promotion explained 78.68% of the total variance in health literacy. The scale and its subscales demonstrated strong internal consistency, with high Cronbach’s alpha coefficients ranging from 0.947 to 0.983. CFA confirmed the three-factor model’s goodness-of-fit for the Chinese population. The dimensions of healthcare, disease prevention and health promotion showed high convergent validity with an average variance extracted values ranging from 0.52 to 0.60 and composite reliability values ranging from 0.94 to 0.96. The reliable and valid Chinese version of the HLS-EU-Q47 (HLS19-Q47-CN) developed and evaluated in this study is an important tool for assessing health literacy levels in the Chinese population. Furthermore, as this tool has global applicability, it has the potential to assess health literacy levels across different countries, enabling practical international comparisons.

PMID:39058422 | DOI:10.1093/heapro/daae083

Chem Biodivers. 2024 Jul 26:e202401052. doi: 10.1002/cbdv.202401052. Online ahead of print.

ABSTRACT

A series of diversified glucosamine derivatives (3a-3y) was synthesized and their antifungal activity was examined against four kinds of phytopathogens, Fusarium graminearum (F. graminearum), Fusarium moniliforme (F. moniliforme), Curvularia. lunata (C. lunata), and Rhizoctonia solani (R. solani)which cause seriously economic losses worldwide by affecting crops. The compound 3o showed remarkable antifungal activity against F. graminearum with EC50 values of 3.96 μg/mL, compared to the standard drug triadimefon (10.1μg/mL). 3D-QSAR model with the statistically recommended values (r2 = 0.915, q2=0.872) show that positive charge group and bulky group in the benzyl ring were favorable for the antifungal activity. Enzyme activity assays confirmed that 3o has amoderate inhibition of trehalase with inhibition rate of 51.4%at 5 μg/mL, which is comparable to those of commercial inhibitors validamycin A with inhibition rate of 83.3%.Molecular docking analysis revealed that 3o also had a hydrogen bond interaction with key amino acid residue compared to validoxylamine.

PMID:39058413 | DOI:10.1002/cbdv.202401052

Am Surg. 2024 Jul 26:31348241269407. doi: 10.1177/00031348241269407. Online ahead of print.

ABSTRACT

Background: Despite increasing sub-specialization, general surgeons continue to perform oncologic thoracic surgeries. Our objective was to determine whether general surgery resident participation in thoracic surgery affects surgical quality or oncologic outcomes. We hypothesized that patient outcomes with and without resident participation would be similar. Methods: We retrospectively reviewed the electronic health records of patients with stage 0-IV lung cancer undergoing oncologic pulmonary resection at BLINDED FOR REVIEW during an 11-year period (2012-2022). Patients younger than 18 years or older than 85 years were excluded, as were those who had incomplete follow-up data or were unregistered in our institutional cancer registry. Patients were divided into groups based on whether residents or staff surgeons completed >50% of the critical portions of the operation. We compared 30-day morbidity outcomes, overall survival (OS), and disease-free survival (DFS). Results: Three hundred thirteen patients met inclusion criteria. Demographic and clinical characteristics were similar between groups, as were types of surgical resection and median operative times. A statistical difference was found in the distribution of surgical approach. The odds of morbidity were 65% higher in the Staff group (OR=1.65; 95% CI, 1.007-2.71). Resident participation was not significantly associated with OS or DFS (P =.32 and P =.54, respectively). Discussion: General surgery resident involvement in lung cancer operations is not associated with longer operative times but is associated with a higher likelihood of a thoracotomy. General surgery resident involvement was associated with decreased postoperative morbidity and did not significantly affect OS or DFS.

PMID:39058406 | DOI:10.1177/00031348241269407

J Periodontal Implant Sci. 2024 Jul 10. doi: 10.5051/jpis.2304040202. Online ahead of print.

ABSTRACT

PURPOSE: This review was conducted to systematically assess the impact of bisphosphonates (BPs) and denosumab, used as anti-resorptive therapies, on the incidence of dental implant failure.

METHODS: Electronic and manual searches were performed in accordance with the described search protocol. Only articles that met the inclusion criteria were selected. The primary outcome was implant failure, while secondary outcomes included biological complications and comorbidities. Following data extraction, a quality assessment and meta-analysis were conducted.

RESULTS: Fourteen eligible studies were included in the analysis following a qualitative evaluation. BP administration, regardless of the timing of anti-resorptive therapy, did not significantly increase the risk of implant failure (odds ratio [OR], 1.40; 95% confidence interval, 0.83-2.34). Subgroup analysis revealed a slightly higher, although statistically insignificant, risk of failure in patients with a follow-up period of 3 years or more compared to those with a follow-up duration of less than 3 years (with ORs of 2.82 and 1.53, respectively). Due to a lack of eligible studies, a meta-analysis for denosumab could not be conducted.

CONCLUSIONS: Our findings suggest that BP treatment does not compromise the survival of dental implants. Specifically, in patients with osteoporosis, implant failure rates were not significantly influenced by the administration of BPs before the placement of dental implants, suggesting that low-dose BP therapy may not contraindicate implant placement. Nevertheless, regular check-ups and maintenance periodontal treatment must not be neglected, and concomitant biological factors should be considered to ensure the long-term success of implant rehabilitation.

PMID:39058350 | DOI:10.5051/jpis.2304040202

J Orthop Trauma. 2024 Jul 23. doi: 10.1097/BOT.0000000000002874. Online ahead of print.

ABSTRACT

OBJECTIVES: To evaluate the risk of developing a new mental disorder diagnosis within two years of lower extremity fracture.

METHODS: Design: Retrospective cohort study.

SETTING: National insurance claims database.

PATIENT SELECTION CRITERIA: Included were patients between the ages of 18 and 65 with lower extremity, pelvis and acetabular fractures without prior mental disorders as defined with ICD-9 and ICD-10 diagnosis codes. Mental disorders evaluated included alcohol use disorder, generalized anxiety disorder, bipolar disorder, major depressive disorder, drug use disorder, panic disorder, post-traumatic stress disorder, and suicide attempt.Outcome Measures and Comparisons: The individual lower extremity fracture cohorts were matched 1:4 with non-fracture controls. The specific groups of interest were pelvis fractures, acetabulum fractures, proximal femur fractures, femoral shaft fractures, distal femur fractures, patella fractures, tibia plateau fractures, tibia shaft fractures, ankle fractures, pilon fractures, calcaneus fractures, and Lisfranc fractures. Rates of mental disorders after primary lower extremity fractures within two years were compared using multivariable logistic regression.

RESULTS: Overall, the 263,988 patient fracture group was 57.2% female with an average age of 46.6 years. Compared to controls with no fracture, patients who sustained pelvis, acetabulum, proximal femur, femoral shaft, distal femur, patella, tibia plateau, tibia shaft, pilon, calcaneus, or Lisfranc fracture had a statistically significant increased risk of being diagnosed with a queried mental disorder within two years of fracture. When comparing all fracture patients by location, those suffering from fractures proximal to the knee joint, including pelvis fractures (OR: 1.51, 95% CI: 1.39-1.64) and proximal femur fractures (OR: 1.36, 95% CI: 1.26-1.47), demonstrated greater risk of developing any of the queried mental disorders compared fractures distal to the knee, including ankle fractures (OR: 0.99, 95% CI: 0.95-1.03) and pilon fractures (OR: 1.05, 95% CI: 0.81-1.36). When comparing specific fracture patients to patients without fracture by mental disorder, patients demonstrated an increased risk of suicide attempt following fracture of the pelvis, acetabulum, femoral shaft, distal femur, and calcaneus, as well as patients suffering a Lisfranc fracture.

CONCLUSIONS: There is an increased risk of being diagnosed with a new mental disorder following lower extremity trauma in patients without prior mental disorder diagnosis compared to matched individuals without a lower extremity fracture. Among the fractures studied, those that were more proximal, such as pelvis and proximal femur fractures, carried the greatest risk compared to more distal fracture sites, including ankle and pilon fractures. Patients who experienced certain lower extremity fractures had a significantly higher rate of suicide attempt compared to patients without fracture. Physicians should consider increased mental health screening and potential referral for mental health evaluation for patients following lower extremity trauma.

LEVEL OF EVIDENCE: Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.

PMID:39058344 | DOI:10.1097/BOT.0000000000002874

Int J Radiat Biol. 2024 Jul 26:1-12. doi: 10.1080/09553002.2024.2381482. Online ahead of print.

ABSTRACT

PURPOSE: Epidemiological studies of stochastic radiation health effects such as cancer, meant to estimate risks of the adverse effects as a function of radiation dose, depend largely on estimates of the radiation doses received by the exposed group under study. Those estimates are based on dosimetry that always has uncertainty, which often can be quite substantial. Studies that do not incorporate statistical methods to correct for dosimetric uncertainty may produce biased estimates of risk and incorrect confidence bounds on those estimates. This paper reviews commonly used statistical methods to correct radiation risk regressions for dosimetric uncertainty, with emphasis on some newer methods. We begin by describing the types of dose uncertainty that may occur, including those in which an uncertain value is shared by part or all of a cohort, and then demonstrate how these sources of uncertainty arise in radiation dosimetry. We briefly describe the effects of different types of dosimetric uncertainty on risk estimates, followed by a description of each method of adjusting for the uncertainty.

CONCLUSIONS: Each of the method has strengths and weaknesses, and some methods have limited applicability. We describe the types of uncertainty to which each method can be applied and its pros and cons. Finally, we provide summary recommendations and touch briefly on suggestions for further research.

PMID:39058334 | DOI:10.1080/09553002.2024.2381482

JMIR Med Inform. 2024 Jul 24;12:e49865. doi: 10.2196/49865.

ABSTRACT

BACKGROUND: Interpretability and intuitive visualization facilitate medical knowledge generation through big data. In addition, robustness to high-dimensional and missing data is a requirement for statistical approaches in the medical domain. A method tailored to the needs of physicians must meet all the abovementioned criteria.

OBJECTIVE: This study aims to develop an accessible tool for visual data exploration without the need for programming knowledge, adjusting complex parameterizations, or handling missing data. We sought to use statistical analysis using the setting of disease and control cohorts familiar to clinical researchers. We aimed to guide the user by identifying and highlighting data patterns associated with disease and reveal relations between attributes within the data set.

METHODS: We introduce the attribute association graph, a novel graph structure designed for visual data exploration using robust statistical metrics. The nodes capture frequencies of participant attributes in disease and control cohorts as well as deviations between groups. The edges represent conditional relations between attributes. The graph is visualized using the Neo4j (Neo4j, Inc) data platform and can be interactively explored without the need for technical knowledge. Nodes with high deviations between cohorts and edges of noticeable conditional relationship are highlighted to guide the user during the exploration. The graph is accompanied by a dashboard visualizing variable distributions. For evaluation, we applied the graph and dashboard to the Hamburg City Health Study data set, a large cohort study conducted in the city of Hamburg, Germany. All data structures can be accessed freely by researchers, physicians, and patients. In addition, we developed a user test conducted with physicians incorporating the System Usability Scale, individual questions, and user tasks.

RESULTS: We evaluated the attribute association graph and dashboard through an exemplary data analysis of participants with a general cardiovascular disease in the Hamburg City Health Study data set. All results extracted from the graph structure and dashboard are in accordance with findings from the literature, except for unusually low cholesterol levels in participants with cardiovascular disease, which could be induced by medication. In addition, 95% CIs of Pearson correlation coefficients were calculated for all associations identified during the data analysis, confirming the results. In addition, a user test with 10 physicians assessing the usability of the proposed methods was conducted. A System Usability Scale score of 70.5% and average successful task completion of 81.4% were reported.

CONCLUSIONS: The proposed attribute association graph and dashboard enable intuitive visual data exploration. They are robust to high-dimensional as well as missing data and require no parameterization. The usability for clinicians was confirmed via a user test, and the validity of the statistical results was confirmed by associations known from literature and standard statistical inference.

PMID:39046780 | DOI:10.2196/49865

Interact J Med Res. 2024 Jul 24;13:e55699. doi: 10.2196/55699.

ABSTRACT

BACKGROUND: The interrelation between COVID-19 and various cardiovascular and metabolic disorders has been a critical area of study. There is a growing need to understand how comorbidities such as cardiovascular diseases (CVDs) and metabolic disorders affect the risk and severity of COVID-19.

OBJECTIVE: The objective of this study is to systematically analyze the association between COVID-19 and cardiovascular and metabolic disorders. The focus is on comorbidity, examining the roles of CVDs such as embolism, thrombosis, hypertension, and heart failure, as well as metabolic disorders such as disorders of glucose and iron metabolism.

METHODS: Our study involved a systematic search in PubMed for literature published from 2000 to 2022. We established 2 databases: one for COVID-19-related articles and another for CVD-related articles, ensuring all were peer-reviewed. In terms of data analysis, statistical methods were applied to compare the frequency and relevance of MeSH (Medical Subject Headings) terms between the 2 databases. This involved analyzing the differences and ratios in the usage of these terms and employing statistical tests to determine their significance in relation to key CVDs within the COVID-19 research context.

RESULTS: The study revealed that “Cardiovascular Diseases” and “Nutritional and Metabolic Diseases” were highly relevant as level 1 Medical Subject Headings descriptors in COVID-19 comorbidity research. Detailed analysis at level 2 and level 3 showed “Vascular Disease” and “Heart Disease” as prominent descriptors under CVDs. Significantly, “Glucose Metabolism Disorders” were frequently associated with COVID-19 comorbidities such as embolism, thrombosis, and heart failure. Furthermore, iron deficiency (ID) was notably different in its occurrence between COVID-19 and CVD articles, underlining its significance in the context of COVID-19 comorbidities. Statistical analysis underscored these differences, highlighting the importance of both glucose and iron metabolism disorders in COVID-19 research.

CONCLUSIONS: This work lays the foundation for future research that utilizes a knowledge-based approach to elucidate the intricate relationships between these conditions, aiming to develop more effective health care strategies and interventions in the face of ongoing pandemic challenges.

PMID:39046774 | DOI:10.2196/55699

Elife. 2024 Jul 24;13:RP95328. doi: 10.7554/eLife.95328.

ABSTRACT

Antimicrobial resistance (AMR) poses a significant threat to human health. Although vaccines have been developed to combat AMR, it has proven challenging to associate specific vaccine antigens with AMR. Bacterial plasmids play a crucial role in the transmission of AMR. Our recent research has identified a group of bacterial plasmids (specifically, IncHI plasmids) that encode large molecular mass proteins containing bacterial immunoglobulin-like domains. These proteins are found on the external surface of the bacterial cells, such as in the flagella or conjugative pili. In this study, we show that these proteins are antigenic and can protect mice from infection caused by an AMR Salmonella strain harboring one of these plasmids. Furthermore, we successfully generated nanobodies targeting these proteins, that were shown to interfere with the conjugative transfer of IncHI plasmids. Considering that these proteins are also encoded in other groups of plasmids, such as IncA/C and IncP2, targeting them could be a valuable strategy in combating AMR infections caused by bacteria harboring different groups of AMR plasmids. Since the selected antigens are directly linked to AMR itself, the protective effect extends beyond specific microorganisms to include all those carrying the corresponding resistance plasmids.

PMID:39046772 | DOI:10.7554/eLife.95328