Nevin Manimala

Sci Rep. 2025 Jan 2;15(1):169. doi: 10.1038/s41598-024-84069-w.

ABSTRACT

Cancers of the mesothelium, such as malignant mesothelioma (MM), historically have been attributed solely to exposure to asbestos. Recent large scale genetic and genomic functional studies now show that approximately 20% of all human mesotheliomas are causally linked to highly penetrant inherited (germline) pathogenic mutations in numerous cancer related genes. The rarity of these mutations in humans makes it difficult to perform statistically conclusive genetic studies to understand their biological effects. This has created a disconnect between functional and epidemiological studies. However, since the molecular pathogenesis of MM in mice accurately recapitulates that of human disease, this disconnect between functional and epidemiological studies can be overcome by using inbred mouse strains that harbor mutation(s) in genes involved in the disease. Most mouse studies have focused on the effect of asbestos exposure, leaving the effects of genetic mutations in the absence of exposure understudied. Here, using existing peer-reviewed studies, we investigate the rate of spontaneous MM among mice with and without germline genetic mutations, in the absence of asbestos exposure. We leveraged these published data to generate a historical control dataset (HCD) to allow us to improve statistical power and account for genetic heterogeneity between studies. Our Bayesian analyses indicate that the odds of spontaneous MM among germline BAP1 mutant mice is substantially larger than that of wildtype mice. These results support the existing biological study findings that mesotheliomas can arise in the presence of pathogenic germline mutations, independently of asbestos exposure.

PMID:39747518 | DOI:10.1038/s41598-024-84069-w

Sci Rep. 2025 Jan 2;15(1):601. doi: 10.1038/s41598-024-84261-y.

ABSTRACT

Transcription factors (TFs), including steroidogenic factor-1 (SF-1), T-box transcription factor (TPIT) and pituitary transcription factor-1 (PIT-1), play a pivotal role in the cytodifferentiation of adenohypophysis. However, the impact of TFs on the growth patterns of nonfunctioning pituitary adenomas (NFPAs) remains unclear. This study aims to investigate the correlation between the expression of TFs and NFPAs growth patterns. Preoperative MRI in 171 patients who underwent surgery for nonfunctioning pituitary macroadenomas were analyzed to determine tumor growth patterns. Immunohistochemical staining for transcription factors PIT-1, TPIT, and SF-1 was done on all samples. Extrasellar growth was divided into three principal directions: infrasellar, suprasellar and lateral cavernous sinus invasion (CSI). Suprasellar extension was defined as tumor extension superior to the tuberculum sellae-dorsum sellae line, inferior extension as invasion through the sellar floor into the sphenoid sinus or clivus and CSI as Knosp grading score of 3 ~ 4. Statistical analysis to compare the groups was conducted using the Fisher’s exact test and t-test. TPIT-expressing tumors were more likely to exhibit combined infrasellar extension (55.17 vs 17.70%, p < 0.0001), as well as isolated infrasellar extension (18.97 vs 0%, p < 0.0001) compared to SF-1-expressing tumors. Conversely, SF-1-expressing tumors were more likely to exhibit combined suprasellar extension (92.92 vs 77.59%, p = 0.0061), as well as isolated suprasellar extension (75.22 vs 41.38%, p < 0.0001). TPIT-expressing tumors had a significantly higher CSI invasion (55.17 vs 35.40%, p = 0.0148). The mean maximal tumor diameter in TPIT and SF-1 macroadenomas was similar (28 vs 26 mm, p = 0.1213). The expression of TFs affects the extrasellar growth pattern of NFPAs. TPIT tumors exhibit a higher propensity for bone invasion and CSI, while SF-1 tumors tend to extend into the suprasellar region. Isolated infrasellar extension is specific to TPIT tumors and can serve as a radiologic sign to distinguish between TPIT tumors and SF-1 tumors.

PMID:39747515 | DOI:10.1038/s41598-024-84261-y

Sci Rep. 2025 Jan 2;15(1):74. doi: 10.1038/s41598-024-84026-7.

ABSTRACT

Acute mesenteric ischaemia (AMI) is a sudden onset of impaired bowel perfusion. Has a high mortality rate and is difficult to diagnose. Therapy involves endovascular, surgical, or a combination of both. Because of baseline differences, the comparison between endovascular and open surgical treatment is subject to selection bias. The aim of this study was to evaluate the results of treatment of AMI by open or endovascular approach in combination with laparotomy, and evaluation of treatment strategy in similar situations. Clinical data from 21 patients treated for AMI between 2018 and 2022 were retrospectively reviewed and compared. The primary endpoint of the study was in-hospital mortality. The secondary endpoint was the statistical evaluation of risk factors for mortality. All patients underwent acute endovascular revascularisation. Aspiration thromboembolectomy was performed in nine patients, stenting in seven, PTA in one and surgery in three. Endovascular therapy was unsuccessful for technical reasons in 3 patients. None of the monitored parameters reached statistical significance. The best results were achieved in the early diagnosis group. The overall mortality of acute mesenteric ischaemia in our cohort was 34.8%. Acute mesenteric ischaemia is a serious condition affecting mainly elderly patients with a high mortality rate, but the diagnosis of mesenteric ischaemia is not an automatic death sentence. To achieve the best therapeutic outcome, mesenteric ischaemia needs to be diagnosed and treated at an early stage. The best therapeutic outcomes are achieved in centres with 24-hour access to endovascular revascularisation and surgical therapy.

PMID:39747507 | DOI:10.1038/s41598-024-84026-7

Ecotoxicol Environ Saf. 2024 Dec 31;290:117637. doi: 10.1016/j.ecoenv.2024.117637. Online ahead of print.

ABSTRACT

INTRODUCTION: Expanding evidence suggests beneficial impacts of greenspace on human health, yet the relationships between greenness and stillbirth remain unknown. This study aimed to quantify the risk and burden of stillbirth associated with maternal greenness exposure during pregnancy.

METHODS: A total of 3,982,304 eligible birth records across 31 provinces in Iran from 2013 to 2018 were included in this study. Greenness exposure during pregnancy was assessed using the satellite-based normalized difference vegetation index (NDVI) and enhanced vegetation index (EVI) with multiple buffers. Stillbirth was defined as the birth of babies with no signs of life at ≥22 weeks of gestation. Multivariable-adjusted logistic regression models were employed to investigate greenness-stillbirth associations. To estimate the exposure-response functions, greenness exposures were fitted as smooth terms using restricted cubic splines. Avoidable burden of stillbirth under the predefined scenarios of improved greenness was estimated through a counterfactual analysis.

RESULTS: A total of 29,770 stillbirths occurred during 2013-2018, totaling to an overall annual rate of 748 cases per 100,000 births. Lower stillbirth risks were consistently seen in pregnant mothers being exposed to greater greenness within buffers of 500-3000 m. For instance, per 0.1-unit increase of NDVI and EVI within a 3000-m buffer was associated with the estimated odds of 0.971 (95 % confidence interval: 0.963-0.978) and 0.957 (0.947-0.968) for stillbirth, respectively. Evidently nonlinear relationships were identified between greenness exposure and stillbirth, exhibiting approximately an inverted L-shaped pattern with the steeper slope at high greenness levels. Assuming causality, 34-41 stillbirths per 100,000 births could be avoidable by achieving the 80th percentile of NDVI/EVI during 2013-2018, representing 4.6-5.4 % of nationwide registry-based stillbirths in Iran.

CONCLUSIONS: Our findings provided robust national evidence on beneficial effects of surrounding greenness in alleviating risk and burden of stillbirth in Iran, suggesting a greener environment could potentially serve as a promising intervention strategy for reducing stillbirth risk in less developed countries.

PMID:39746225 | DOI:10.1016/j.ecoenv.2024.117637

Biomed Phys Eng Express. 2025 Jan 2. doi: 10.1088/2057-1976/ada4b6. Online ahead of print.

ABSTRACT

Clinical adoption of innovative EEG technology is contingent on the non-inferiority of the new devices relative to conventional ones. We present the four key results from testing the signal quality of Zeto’s WR19 EEG system against a conventional EEG system conducted on patients in a clinical setting. &#xD;Methods: We performed 30-minute simultaneous recordings using the Zeto WR19 (zEEG) and a conventional clinical EEG system (cEEG) in a cohort of 15 patients. We compared the signal quality between the two EEG systems by computing time domain statistics, waveform correlation, spectral density, signal-to-noise ratio, and signal stability. &#xD;Results: All statistical comparisons resulted in signal quality non-inferior relative to cEEG. (i) Time domain statistics, including the Hjorth parameters, showed equivalence between the two systems, except for a significant reduction of sensitivity to electric noise in zEEG relative to cEEG. (ii) The point-by-point waveform correlation between the two systems was acceptable (r>0.6; P<0.001). (iii) Each of the 15 datasets showed a high spectral correlation (r>0.99; P<0.001) and overlapping spectral density across all electrode positions, indicating no systematic signal distortion. (iv) The mean signal-to-noise ratio (SNR) of the zEEG system exceeded that of the cEEG by 4.82 dB, equivalent to a 16% improvement. (v) The signal stability was maintained through the recordings.&#xD;Conclusion: In terms of signal quality, the zEEG system is non-inferior to conventional clinical EEG systems with respect to all relevant technical parameters that determine EEG readability and interpretability. Zeto’s WR19 wireless dry electrode system has signal quality in the clinical EEG space at least equivalent to traditional cEEG recordings.

PMID:39746217 | DOI:10.1088/2057-1976/ada4b6

Obstet Gynecol. 2025 Jan 2. doi: 10.1097/AOG.0000000000005812. Online ahead of print.

ABSTRACT

OBJECTIVE: To assess the efficacy and safety of fezolinetant and elinzanetant for vasomotor symptoms in menopausal women.

DATA SOURCES: MEDLINE, EMBASE, and Cochrane databases were systematically searched until August 22, 2024. Because the Cochrane Library included all the identified randomized controlled trials (RCTs), it was unnecessary to search ClinicalTrials.gov. The following words made up the search strategy, which was applied to the three databases: fezolinetant, elinzanetant, vasomotor symptoms, and menopause.

METHODS OF STUDY SELECTION: Only RCTs comparing fezolinetant and elinzanetant with placebo for vasomotor symptoms in menopausal women were included.

TABULATION, INTEGRATION, AND RESULTS: We extracted the number of patients, mean age, body mass index (BMI), and number of patients who underwent oophorectomy. Data were examined with the Mantel-Haenszel method and 95% CIs. Heterogeneity was assessed with I2 statistics. R 4.3.2 was used for statistical analysis. Seven RCTs with 4,087 patients were included in the analysis. Fezolinetant and elinzanetant were associated with diminished vasomotor symptom frequency: fezolinetant 30 mg (mean difference 2.16, 95% CI, 1.54-2.79, I2=0%), fezolinetant 45 mg (mean difference 2.54, 95% CI, 1.86-3.21, I2=0%), and elinzanetant 120 mg (mean difference 2.99, 95% CI, 1.74-4.23, I2=0%). Both drugs also showed a decrease in vasomotor symptom severity: fezolinetant 30 mg (mean difference 0.20, 95% CI, 0.09-0.33, I2=0%), fezolinetant 45 mg (mean difference 0.24, 95% CI, 0.13-0.34, I2=0%), and elinzanetant 120 mg (mean difference 0.36, 95% CI, 0.26-0.46, I2=0%). Elinzanetant 120 mg showed a significant improvement in sleep quality (mean difference 4.65, 95% CI, 3.73-5.56, I2=0%). Elinzanetant 120 mg was associated with the occurrence of drug-related adverse events (11.70% vs 20.75%, risk ratio [RR] 0.57, 95% CI, 0.39-0.82, I2=19%) and headache (2.54% vs 8.0%, RR 0.32, 95% CI, 0.16-0.64, I2=0%).

CONCLUSION: In this meta-analysis, consistent results suggest that fezolinetant and elinzanetant are associated with beneficial outcomes in menopausal women with vasomotor symptoms. Elinzanetant provided a larger effect size in vasomotor symptom frequency and severity reduction and greatly improved sleep quality compared with fezolinetant.

SYSTEMATIC REVIEW REGISTRATION: PROSPERO, CRD42023469952.

PMID:39746208 | DOI:10.1097/AOG.0000000000005812

Obstet Gynecol. 2025 Jan 2. doi: 10.1097/AOG.0000000000005814. Online ahead of print.

ABSTRACT

OBJECTIVE: To evaluate the correlation in temporal trends in obesity and endometrioid endometrial cancer incidence in the United States using two comprehensive national databases.

METHODS: This is a cohort study in which data on endometrioid endometrial cancer were obtained from the U.S. Cancer Statistics from 2001 to 2018 and corrected for hysterectomy and pregnancy. Data on obesity were collected from the NHANES (National Health and Nutrition Examination Survey) database from 1988 to 2018. Average annual percentage changes (AAPCs) were used to describe trends. Pearson correlation coefficients (r) were calculated to examine the relationship between trends. SEER*Stat 8.3.9.2 and joinpoint regression program 5.2.0 were used for statistical analysis.

RESULTS: From U.S. Cancer Statistics data, 586,742 cases of endometrioid cancer were identified from 2001 to 2018. The average annual increase in endometrioid cancer was as follows: Hispanic 1.37% (95% CI, 1.14-1.60, P<.001), Black 1.30% (95% CI, 1.04-1.57, P<.001), and White -0.17 (95% CI, -0.91 to 0.58, P=.656). Women aged 20-29 years had a 4.48% annual increase (95% CI, 3.72-5.25, P<.001) and women aged 30-39 years had a 3.00% annual increase in rates (95% CI, 2.65-3.36, P<.001). According to the NHANES data, the prevalence of obesity in 2018 in adult women was as follows: Black 56.80%, Hispanic 44.10%, and White 40.90%. An examination of trends by age showed that women aged 20-29 years had the highest annual rise in obesity compared with other age groups (AAPC 7.36%, 95% CI, 4.0-10.8, P<.05). Strong and statistically significant correlations between endometrioid cancer and obesity trends were noted for Black (r=0.78, P=.01) and Hispanic (r=0.91, P<.001) women, as well as women aged 20-29 years (r=0.72, P=.03) and 30-39 years (r=0.88, P=.001).

CONCLUSION: The current data demonstrate a temporal association between the increasing incidence of obesity and endometrioid endometrial cancer, and this effect disproportionately affects younger women and Black and Hispanic women.

PMID:39746203 | DOI:10.1097/AOG.0000000000005814

JMIR Cancer. 2025 Jan 2;11:e55746. doi: 10.2196/55746.

ABSTRACT

BACKGROUND: Survivorship care plans (SCPs), ie, personalized health care plans for cancer survivors, can be used to support the growing group of melanoma survivors throughout their disease trajectory. However, implementation and effectiveness of SCPs are suboptimal and could benefit from the involvement of stakeholders in developing a user-centered design.

OBJECTIVE: The aim of this study was to identify the ideal SCP for patients with melanoma in terms of functions and features to be included according to different stakeholders and to explore their underlying motives.

METHODS: In total, 3 cocreation sessions were organized with mixed samples of stakeholders, ie, patients with (a history of) melanoma (n=4), health care providers (HCPs) active in melanoma care (n=3), and IT specialists active in hospital IT departments (n=6). They were invited to compose their ideal melanoma SCP based on potential functions and features identified from prior qualitative research. These functions and features belonged to one of the four main categories of survivorship care (SSC): (1) information and education, (2) identification and treatment, (3) oncological follow-up, and (4) coordination. Participants were invited to explain their motives for including functions and features. Ideas were shared between stakeholders, and interaction was promoted. Descriptive statistics were used to determine the ideal SCP per stakeholder group. To analyze underlying motives, all cocreation sessions were audio-taped, transcribed verbatim, and analyzed in a thematic content analysis.

RESULTS: With regard to their ideal SCPs, all stakeholders added functions from all 4 SSC categories. Patients assembled a rather compact SCP with category 2 on identification and treatment being most important. Both HCPs and IT professionals constructed a somewhat larger SCP, with category 3 on oncological follow-up being the most important aspect and HCPs also focusing on category 4 on coordination. As for the motives behind their ideal SCP compositions, patients predominantly added functions based on their personal experiences or experiences from fellow patients, whereas both HCPS and IT professionals based their compositions primarily on their respective areas of expertise: HCPs related their additions to their roles as medical practitioners; for example, in providing a complete treatment plan and obtaining informed consent, while IT professionals’ contributions were mainly influenced by feasibility and privacy concerns.

CONCLUSIONS: This cocreation study provides insights into stakeholders’ ideal melanoma SCP and the motivations behind them. Considering the diversity in both the preferences and underlying motives regarding SCP composition between patients, HCPs, and IT specialists, it is crucial to develop a broad SCP that extends beyond traditional SCP content, emphasizing personalization. In addition to continued stakeholder involvement, efforts should be focused on addressing potential feasibility and privacy issues to ensure the SCP meets both patients’ and HCPs’ needs.

PMID:39746197 | DOI:10.2196/55746

J Med Internet Res. 2025 Jan 2;27:e53205. doi: 10.2196/53205.

ABSTRACT

BACKGROUND: Requests for public social care support can be made through an online portal. These digital “front doors” can help people navigate complex social care systems and access services. These systems can be set up in different ways, but there is little evidence about the impact of alternative arrangements. Digital front-door systems should help people better access services, particularly low-intensity services (high-intensity care is likely to require a full in-person assessment).

OBJECTIVE: This study aimed to investigate the association between 2 primary digital front door arrangements, easy-read information, and self-assessment tools provided on official websites, and the type of social care support that is offered: ongoing low-level support (OLLS), short-term care (STC) and long-term care (LTC).

METHODS: Information on front door arrangements was collected from the official websites of 152 English local authorities in 2021. We conducted a cross-sectional analysis using aggregated service use data from official government returns at the local authority level. The independent variables were derived from the policy information collected, specifically focusing on the availability of online digital easy-read information and self-assessment tools for adults and caregivers through official websites. The dependent variables were the rates of using social care support, including OLLS, STC, and LTC, across different age groups: the adult population (aged 18 and older), younger population (aged between 18 and 64 years), and older population (aged 65 and older). Multivariate regression analysis was used to examine the association between digital front door arrangements and access to social care support, controlling for population size, dependency level, and financial need factors.

RESULTS: Less than 20% (27/147) of local authorities provided an integrated digital easy-read format as part of their digital front door system with about 25% (37/147) adopting digital self-assessment within their system. We found that local authorities that offered an integrated digital easy-read information format showed higher rates of using OLLS (β coefficient=0.54; P=.03; but no statistically significant association with LTC and STC). The provision of an online self-assessment system was not associated with service use in the 1-year (2021) cross-sectional estimate, but when 2 years (2020 and 2021) of service-use data were analyzed, a significant positive association was found on OLLS rates (β coefficient=0.41; P=.21). Notably, these findings were consistent across different age groups.

CONCLUSIONS: These findings are consistent with our hypothesis that digital systems with built-in easy-read and self-assessment may make access to (low-intensity) services easier for people. Adoption of these arrangements could potentially help increase the uptake of support among those who are eligible, with expected benefits for their care-related well-being. Given the limited adoption of the digital front door by local authorities in England, expanding their use could improve care-related outcomes and save social care costs.

PMID:39746193 | DOI:10.2196/53205

JMIR Med Inform. 2025 Jan 2;13:e58457. doi: 10.2196/58457.

ABSTRACT

BACKGROUND: In this study, we evaluate the accuracy, efficiency, and cost-effectiveness of large language models in extracting and structuring information from free-text clinical reports, particularly in identifying and classifying patient comorbidities within oncology electronic health records. We specifically compare the performance of gpt-3.5-turbo-1106 and gpt-4-1106-preview models against that of specialized human evaluators.

OBJECTIVE: We specifically compare the performance of gpt-3.5-turbo-1106 and gpt-4-1106-preview models against that of specialized human evaluators.

METHODS: We implemented a script using the OpenAI application programming interface to extract structured information in JavaScript object notation format from comorbidities reported in 250 personal history reports. These reports were manually reviewed in batches of 50 by 5 specialists in radiation oncology. We compared the results using metrics such as sensitivity, specificity, precision, accuracy, F-value, κ index, and the McNemar test, in addition to examining the common causes of errors in both humans and generative pretrained transformer (GPT) models.

RESULTS: The GPT-3.5 model exhibited slightly lower performance compared to physicians across all metrics, though the differences were not statistically significant (McNemar test, P=.79). GPT-4 demonstrated clear superiority in several key metrics (McNemar test, P<.001). Notably, it achieved a sensitivity of 96.8%, compared to 88.2% for GPT-3.5 and 88.8% for physicians. However, physicians marginally outperformed GPT-4 in precision (97.7% vs 96.8%). GPT-4 showed greater consistency, replicating the exact same results in 76% of the reports across 10 repeated analyses, compared to 59% for GPT-3.5, indicating more stable and reliable performance. Physicians were more likely to miss explicit comorbidities, while the GPT models more frequently inferred nonexplicit comorbidities, sometimes correctly, though this also resulted in more false positives.

CONCLUSIONS: This study demonstrates that, with well-designed prompts, the large language models examined can match or even surpass medical specialists in extracting information from complex clinical reports. Their superior efficiency in time and costs, along with easy integration with databases, makes them a valuable tool for large-scale data mining and real-world evidence generation.

PMID:39746191 | DOI:10.2196/58457