Tag: pubmed

Expert Opin Drug Saf. 2025 Feb 2. doi: 10.1080/14740338.2025.2461197. Online ahead of print.

ABSTRACT

OBJECTIVES: This study aimed to describe the pulmonary toxicity of cyclin-dependent kinase 4/6 inhibitors (CDK 4/6 inhibitors) (palbociclib, ribociclib, and abemaciclib) in patients being treated for breast cancer using the Food and Drug Administration Adverse Event Reporting System (FAERS) database.

RESEARCH DESIGN AND METHODS: Disproportionality analysis was performed to assess pulmonary toxicity associated with CDK 4/6 inhibitors. Clinical characteristics, onset time, sensitivity analysis, subgroup analyses, drug combinations, comorbidities, and co-reported events were performed.

RESULTS: Out of 83,505 CDK 4/6 inhibitor-related adverse events (AEs) documented in the FAERS database during the study period, 437 cases of pneumonitis, 555 cases of pulmonary edema, and 181 cases of pulmonary thrombosis related to CDK 4/6 inhibitors were analyzed. Pneumonitis and pulmonary thrombosis had the strongest signal strength in abemaciclib, pulmonary edema had the strongest signal strength in ribociclib. The median latency for pneumonitis, pulmonary edema, and pulmonary thrombosis was 66-173.5 days 27-131 days, and 68-279 days), respectively. Pulmonary toxicity is statistically significant disproportionality in females as well as in patients over 60 years old.

CONCLUSION: Abemaciclib was most strongly associated with pneumonitis and pulmonary thrombosis. Ribociclib was most strongly associated with pulmonary edema. The correlation with pulmonary toxicity was, in descending order, abemaciclib, ribociclib, and palbociclib.

PMID:39894782 | DOI:10.1080/14740338.2025.2461197

J Infect Public Health. 2025 Jan 21;18(4):102677. doi: 10.1016/j.jiph.2025.102677. Online ahead of print.

ABSTRACT

BACKGROUND: Care retention and medication adherence are crucial for individuals living with human immunodeficiency virus (HIV). Discrepancies exist between real-world evidence and randomized trials regarding early antiretroviral therapy (ART) initiation and care retention. We investigated the effects of same-day ART initiation on care and medication discontinuation in new patients with acquired immunodeficiency syndrome (AIDS) and those newly infected with HIV.

METHODS: The two groups commenced ART from January 2017 to December 2021 in Taiwan. Data were collected from the National Health Insurance claims database. We defined care discontinuation as having no clinical visits for over 90 days since the last clinical visit and medication discontinuation as failing to pick up medication 30 days after the expected medication pick-up date. We used a doubly robust weighted Cox regression model to estimate the average hazard ratio for same-day ART initiation compared to rapid ART initiation within 7 days over a 12-month care- and medication-discontinuation risk horizon.

RESULTS: Among the 1528 HIV- and 5373 AIDS-group individuals, 1329 and 4494 initiated same-day ART, respectively. Same-day ART initiation did not impact care or medication discontinuation among HIV-infected patients. However, it was associated with a significantly lower hazard of care discontinuation (adjusted average hazard ratio [aAHR] = 0.86, 95 % CI: 0.74-0.99) and a higher, though not significant, hazard of medication discontinuation (aAHR = 1.14, 95 % CI: 0.86-1.52) among patients with AIDS.

CONCLUSION: Same-day ART initiation demonstrates varying impacts on care and medication continuation. While it improves care retention, caution is advised regarding medication discontinuation among patients with AIDS.

PMID:39893713 | DOI:10.1016/j.jiph.2025.102677

Clin Nutr. 2025 Jan 28;46:117-118. doi: 10.1016/j.clnu.2025.01.027. Online ahead of print.

NO ABSTRACT

PMID:39893704 | DOI:10.1016/j.clnu.2025.01.027

J Chem Inf Model. 2025 Feb 2. doi: 10.1021/acs.jcim.4c01871. Online ahead of print.

ABSTRACT

Chemical reactions are regarded as transformations of chemical structures, and the question of which atoms in the reactants correspond to which atoms in the products has attracted chemists for a long time. Atom-to-atom mapping (AAM) is a procedure that establishes such correspondence(s) between the atoms of reactants and products in a chemical reaction. Currently, automatic AAM tools play a pivotal role in various chemoinformatics tasks. However, achieving accurate automatic AAM for complex or unknown reactions within a reasonable computation time remains a significant challenge due to the combinatorial nature of the problem and the difficulty in applying appropriate reaction rules. In this study, we propose a rule-free AAM algorithm, which enumerates all atom-to-atom correspondences that minimize the number of bond cleavages and formations during the reaction. To reduce the computational burden associated with the combinatorial optimization (i.e., minimizing bond changes), we introduce Ising computing, a computing paradigm that has gained significant attention for its efficiency in solving hard combinatorial optimization problems. We found that our Ising computing framework outperforms conventional combinatorial optimization algorithms in terms of computation times, making it feasible to solve the AAM problem without reaction rules in an acceptable time. Furthermore, our AAM algorithm successfully found the correct AAM solution for all problems in a benchmark data set. In contrast, conventional AAM algorithms based on chemical heuristics failed for several problems. Specifically, these algorithms either failed to find the optimal solution in terms of bond changes, or they identified only one optimal solution, which was incorrect when multiple optimal solutions exist. These results emphasize the importance of enumerating all optimal correspondences that minimize bond changes, which is effectively achieved by our Ising-computing framework.

PMID:39893651 | DOI:10.1021/acs.jcim.4c01871

Cell Rep. 2025 Feb 1;44(2):115240. doi: 10.1016/j.celrep.2025.115240. Online ahead of print.

ABSTRACT

Despite the broad use of single-cell/nucleus RNA sequencing in plant research, accurate cluster annotation in less-studied plant species remains a major challenge due to the lack of validated marker genes. Here, we generated a single-cell RNA sequencing atlas of soil-grown wheat roots and annotated cluster identities by transferring annotations from publicly available datasets in wheat, rice, maize, and Arabidopsis. The predictions from our orthology-based annotation approach were next validated using untargeted spatial transcriptomics. These results allowed us to predict evolutionarily conserved tissue-specific markers and generate cell type-specific gene regulatory networks for root tissues of wheat and the other species used in our analysis. In summary, we generated a single-cell and spatial transcriptomics resource for wheat root apical meristems, including numerous known and uncharacterized cell type-specific marker genes and developmental regulators. These data and analyses will facilitate future cell type annotation in non-model plant species.

PMID:39893633 | DOI:10.1016/j.celrep.2025.115240

Eat Weight Disord. 2025 Feb 2;30(1):11. doi: 10.1007/s40519-025-01717-4.

ABSTRACT

PURPOSE: Exploring novel mediators affecting the relationship between obesity and sleep-disordered breathing (SDB) is necessary. This study aimed to explore the mediating role of the non-high-density lipoprotein cholesterol to high-density lipoprotein cholesterol ratio (NHHR) in the association between body mass index (BMI) and SDB using data from the 2015-2018 National Health and Nutrition Examination Survey (NHANES) cycles.

METHODS: Total 7639 participants were included. SDB was defined based on the self-reported frequency of snoring, snorting, or excessive daytime sleepiness. The BMI and NHHR were calculated based on height and weight measurements and laboratory data, respectively. Weighted multivariate logistic and linear regression analyses were conducted to examine the associations, and restricted cubic spline (RCS) analysis was used to assess dose-response relationships. Mediation analysis was performed to evaluate the NHHR’s role in the BMI-SDB association. Subgroup analyses were performed to assess differences across various populations.

RESULTS: SDB symptoms were observed in 51.05% of participants. Higher BMI was significantly associated with increased SDB risk. RCS analysis revealed a nonlinear relationship between BMI and SDB. Subgroup analyses indicated a positive correlation between BMI and SDB was stronger among nonhypertensive participants. NHHR was positively associated with BMI and SDB. Mediation analysis showed that the NHHR explained 5.44-8.12% of the BMI-SDB association.

CONCLUSIONS: BMI is a critical factor in the risk of SDB, and the NHHR partially mediates this relationship. BMI and cholesterol levels should be managed to mitigate the SDB risk.

LEVEL OF EVIDENCE: Level V-cross-sectional observational study.

PMID:39893618 | DOI:10.1007/s40519-025-01717-4

Environ Monit Assess. 2025 Feb 2;197(3):225. doi: 10.1007/s10661-025-13623-4.

ABSTRACT

This research reports heavy metal pollution in riverine sediments from River Kabul, Pakistan, which could endanger human health and ecology via the food web. The results revealed a substantial special variation in the average contents (mg/kg) of chromium (Cr), manganese (Mn), cobalt (Co), nickel (Ni), copper (Cu), zinc (Zn), cadmium (Cd), mercury (Hg), lead (Pb), iron (Fe), and aluminum (Al) in riverine sediments, in the order of Fe (20,234.51) > Al (17,550.86) > Mn (375.45) > Zn (149.08) > Ni (89.11) > Cr (83.36) > Pb (45.29) > Cu (19.86) > Cd (7.48) > Co (6.28) > Hg (0.81). Among the heavy metals, Cd exhibited the highest degree of pollution along the river, followed by Hg > Ni > Zn > Pb > Al > Cr > Mn > Fe > Cu > Co. The overall contamination factor (CF) values for the sum of heavy metals were highest at monitoring site S-9, followed by S-8 > S-10 > S-6 > S-5 > S-7 > S-1 > S-4 > S-12 > S-3 > S-2 > S-1 with pollution load index (PLI) > 1, whereas the geo-accumulation index (Igeo) values of Cd and Hg fluctuated between Levels 3, 4, and 6, suggesting moderate to extreme pollution in the river. The correlation statistics determined the fate and distribution of heavy metals by establishing significant positive correlations between the specific metals of bounded sediments. The cluster analysis separates the correlated metals into Groups A and B, and Groups 1 and 2. While the principal component analysis evaluates the qualitative behavior of clustering by discerning industrial, agrochemicals, mining, and domestic wastewater discharges, leakages of lubricants along with multiple geogenic inputs, erosion of mafic and ultramafic rocks, and minimal atmospheric deposition are all potential sources of Cr, Mn, Co, Ni, Cu, Zn, Cd, Hg, Pb, Fe, and Al contamination. In terms of risk, the contaminations of Mn, Co, Cu, Zn, and Pb in riverine sediments were 85, 100, 100, 17, and 11%, respectively, representing a rare biological influence because their value is less than their corresponding threshold effect concentrations (TECs), whereas the levels of Mn, Ni, Cd, and Hg were above their probable effect concentrations (PECs) of 100, 100, 81, and 52%, respectively, representing prominent adverse biological influence. Based on consensus-based TECs and PECs, the contamination levels of Cr, Mn, Zn, Cd, Hg, and Pb were 100, 85, 83, 19, 48, and 90%, respectively, indicating occasionally exhibited adverse biological effects on the riverine population. Besides, the overall potential ecological risk index (PERI) of Cd and Hg, in particular, exhibited the maximum pollution level ( $E_{\text{r}}^{\text{i}}$ ≥ 320), suggesting a very high potential ecological risk in the drainage that requires special attention from pollution control authorities.

PMID:39893612 | DOI:10.1007/s10661-025-13623-4

Endocrine. 2025 Feb 2. doi: 10.1007/s12020-025-04176-0. Online ahead of print.

ABSTRACT

PURPOSE: Hyperprolactinemia in children and adolescents can result from various etiologies, including pituitary masses. Understanding the underlying causes, clinical presentation, and outcomes is essential for effective management.

METHOD: A retrospective cohort study was conducted, analyzing clinical data from patients diagnosed with hyperprolactinemia secondary to pituitary masses. The study included patients aged under 18 years, who were diagnosed between January 2018 and September 2024. Patients were classified into two groups: those with prolactinoma and those with non-prolactinoma causes, including non-functioning pituitary adenomas (NFPAs) and craniopharyngiomas. Serum prolactin levels, imaging studies, and treatment responses were assessed.

RESULTS: A total of 33 patients with hyperprolactinemia attributed to pituitary masses were identified. The diagnoses among the patients were as follows: 54.5% had prolactinomas, 24.2% had NFPAs, and 21.2% had craniopharyngiomas. The age at diagnosis ranged from 8.4-17.9 years. In the prolactinoma group, the mean age at diagnosis was 15.6 ± 2.1 years, while in the non-prolactinoma group, it was 13.5 ± 2.9 years, and a statistically significant difference was observed (p = 0.024). The median prolactin level was 258 ng/mL (range: 30.5-14,35 0 ng/mL). According to the diagnoses, the median prolactin level was 491.5 ng/mL (range: 249-14,350 ng/mL) for prolactinomas, 45.6 ng/mL (range: 30.5-68.5 ng/mL) for NFPAs, and 61 ng/mL (range: 44-72 ng/mL) for craniopharyngiomas. Menstrual irregularities, headaches, and galactorrhea were the most commonly reported complaints. Overweight/obesity was present in 39.3% of the entire cohort, while patients with prolactinomas demonstrated a significant reduction in BMI SDS following cabergoline treatment. Cabergoline treatment achieved a 100% success rate in patients with prolactinomas.

CONCLUSION: We observed a higher prevalence of hyperprolactinemia due to NFPAs and craniopharyngiomas compared to previous reports. Notably, obesity was prevalent among patients and demonstrated a favorable response to cabergoline therapy. These findings emphasize the necessity for future studies, particularly larger prospective trials incorporating genetic analyses, to enhance our understanding of the characteristics and treatment outcomes of pediatric hyperprolactinemia.

PMID:39893604 | DOI:10.1007/s12020-025-04176-0

J Assoc Physicians India. 2025 Jan;73(1):e8-e13. doi: 10.59556/japi.73.0772.

ABSTRACT

OBJECTIVE: Denosumab, a human monoclonal antibody that exhibits strong affinity and specificity for the receptor activator of nuclear factor-kappa B ligand (RANK-L), is essential in regulating bone turnover. Its inhibition of RANK-L decreases bone resorption by preventing the development, function, and survival of osteoclasts. The objective of the study was to evaluate and compare the efficacy and safety of biosimilar denosumab with the reference product, Prolia (denosumab), in Indian women suffering from postmenopausal osteoporosis.

METHODS: This phase III study was a prospective, active-controlled, randomized, double-blind trial that included postmenopausal women diagnosed with osteoporosis. Participants were randomly allocated in a 2:1 ratio to receive either the biosimilar denosumab (Treatment A) or the reference denosumab (Prolia®; Treatment B). All participants also received daily supplementation of 500 international units (IU) of vitamin D3 and 1000 mg calcium. The primary outcomes measured were the bone mineral density (BMD) percentage change at the lumbar spine and the neck of femur, while the secondary endpoint assessed changes in biomarkers from baseline at months 6 and 12.

RESULTS: The lumbar spine BMD percentage change for group A vs group B from baseline to month 6 was 5.69 ± 0.88 (p < 0.0001) vs 5.08 ± 1.19 (p < 0.0001), and at 12 months was 7.26 ± 1.05 (p < 0.0001) vs 7.31 ± 1.40 (p < 0.0001), demonstrating equivalent efficacy. Both treatment groups showed statistically significant improvement in femoral neck BMD at 12 months. No statistically significant difference was noted in the ln-transformed primary pharmacokinetic parameters, including C-max, AUC0-120d, and AUC0-∞.

CONCLUSION: Biosimilar denosumab was comparable to reference denosumab with respect to its efficacy, safety, pharmacokinetics (PK), pharmacodynamics, and immunogenicity in women with postmenopausal osteoporosis. Thus, biosimilar denosumab is expected to improve the quality of life in osteoporotic patients at affordable prices.

PMID:39893524 | DOI:10.59556/japi.73.0772

Crit Rev Clin Lab Sci. 2025 Feb 1:1-30. doi: 10.1080/10408363.2025.2453152. Online ahead of print.

ABSTRACT

Monitoring individuals’ laboratory data is essential for assessing their health status, evaluating the effectiveness of treatments, predicting disease prognosis and detecting subclinical conditions. Currently, monitoring is performed intermittently, measuring serum, plasma, whole blood, urine and occasionally other body fluids at predefined time intervals. The ideal monitoring approach entails continuous measurement of concentration and activity of biomolecules in all body fluids, including solid tissues. This can be achieved through the use of biosensors strategically placed at various locations on the human body where measurements are required for monitoring. High-tech wearable biosensors provide an ideal, noninvasive, and esthetically pleasing solution for monitoring individuals’ laboratory data. However, despite significant advances in wearable biosensor technology, the measurement capacities and the number of different analytes that are continuously monitored in patients are not yet at the desired level. In this review, we conducted a literature search and examined: (i) an overview of the background of monitoring for personalized laboratory medicine, (ii) the body fluids and analytes used for monitoring individuals, (iii) the different types of biosensors and methods used for measuring the concentration and activity of biomolecules, and (iv) the statistical algorithms used for personalized data analysis and interpretation in monitoring and evaluation.

PMID:39893518 | DOI:10.1080/10408363.2025.2453152