Tag: nevin manimala

JCO Glob Oncol. 2025 Jan;11:e2400431. doi: 10.1200/GO-24-00431. Epub 2025 Jan 2.

ABSTRACT

PURPOSE: Metastatic urothelial carcinoma (mUC) poses a challenge to health care systems, given its treatment complexity and mortality. We aimed to describe the characteristics, treatment patterns, and survival outcomes of Mexican patients with mUC.

METHODS: A retrospective study was conducted across eight centers for adults with mUC from January /2001 to December 2021. We recorded medical history, eligibility for first-line platinum therapy, treatment lines received, and access to novel drugs. Descriptive statistics were used and survival analysis, including Kaplan-Meier curves and Cox proportional hazards model, was performed.

RESULTS: We identified 379 patients with mUC; 37 were excluded, and 76% was male, with a median age of 67 years. The median follow-up was 8.4 months. Among those who received a first-line treatment (65%), cisplatin-based chemotherapy (45%) was the most common followed by carboplatin (39%). Causes of cisplatin ineligibility were Eastern Cooperative Oncology Group ≥2 (41%) and glomerular filtration rate <60 mL/min (33%). The overall response rate to up-front platinum therapy was 33%, with a median progression-free survival of 6.1 months (95% CI, 4.9 to 6.9). Second-, third-, and fourth-line treatment was given to 24.6%, 8.8%, and 3.5%, respectively. Chemotherapy was the most common regimen prescribed. Access to novel drugs was limited, 14 patients received avelumab, and 25% received immunotherapy as second-line treatment. The median overall survival was 11.8 months (95% CI, 10.2 to 15.2). Multivariate analysis showed that first-line treatment was independently associated with better survival, whereas poor performance status and visceral disease were associated with worse survival.

CONCLUSION: To our knowledge, these data represent the first effort to delineate treatment trends of mUC in Mexico. First-line treatment prescription and rates of progression to platinum therapy were higher than those described worldwide. Factors affecting survival included performance status, first-line treatment, and visceral disease. Our study highlights unequal access to novel treatments, underscoring the need for equitable care.

PMID:39746168 | DOI:10.1200/GO-24-00431

J Clin Oncol. 2025 Jan 2:JCO2401875. doi: 10.1200/JCO-24-01875. Online ahead of print.

ABSTRACT

PURPOSE: In light of evolving evidence that some patients with node-positive estrogen receptor-positive (ER+) disease may receive less benefit from chemotherapy, this study reports 12-year outcomes of the C9741 trial overall, and by the sensitivity to endocrine therapy (SET2,3) test index, a biomarker measuring endocrine transcriptional activity, to identify patients most likely to benefit from dose-dense chemotherapy.

METHODS: In all, 1,973 patients were randomly assigned to dose-dense versus conventional chemotherapy. Hazard ratios (HRs) for prognosis and for predictive interaction with chemotherapy schedule were estimated from Cox models of long-term disease-free survival (DFS) and overall survival (OS). SET2,3 was tested on the 682 banked RNA samples from ER+ cancers.

RESULTS: Dose-dense chemotherapy improved DFS in the overall study population by 23% (HR, 0.77 [95% CI, 0.66 to 0.90]) and OS by 20% (HR, 0.80 [95% CI, 0.67 to 0.95]); the benefits of dose-dense therapy were seen for ER+ and ER-negative subsets, without significant interaction between treatment arm and ER status. Low SET2,3 status was highly prognostic, but also predicted improved outcomes from dose-dense chemotherapy (interaction P = .0998 for DFS; 0.027 for OS), independent of menopausal status. Specifically, low endocrine transcriptional activity predicted benefit from dose-dense chemotherapy, whereas tumor burden and proliferation-driven signatures for molecular subtype classification did not.

CONCLUSION: At 12-year follow-up, C9741 confirmed the sustained long-term benefit of adjuvant dose-dense chemotherapy for node-positive breast cancer. SET2,3 identified patients with ER+ breast cancer who benefited from dose-dense chemotherapy, and specifically, this benefit was predicted by low endocrine activity in the cancer, rather than tumor burden, molecular subtype, or menopausal status.

PMID:39746162 | DOI:10.1200/JCO-24-01875

J Am Chem Soc. 2025 Jan 2. doi: 10.1021/jacs.4c13999. Online ahead of print.

ABSTRACT

We recently reported a chiral phosphoric acid (CPA) catalyzed enantioselective photomediated ring contraction of piperidines and other saturated heterocycles. By extruding a single heteroatom from a ring, this transformation builds desirable C(sp³)-C(sp³) bonds in the ring contracted products; however, the origins of enantioselectivity remain poorly understood. In this work, enantioselectivity of the ring contraction has been explored across an expanded structurally diverse substrate scope, revealing a wide range of enantioselectivities (0-99%) using two distinct CPA catalysts. Mechanistic investigations support rate-determining excitation that generates short-lived achiral intermediates that are intercepted by the CPA in an enantiodetermining ring closure. The effects of competitive uncatalyzed reactivity and light-driven reversibility of the enantiodetermining ring closure on enantioselectivity have been elucidated. Statistical models were built by regressing the range of enantioselectivities from the substrate scope against key structural features of the products for both CPA catalysts. The resultant models suggested distinct factors that influence the enantioselectivity response for each catalyst and enabled rational modification of a pharmaceutically relevant target molecule to improve enantioselectivity. Finally, density functional theory (DFT)-based transition state analysis identified distinct noncovalent interactions with each catalyst that correlated with the unique selectivity-relevant features uncovered through statistical modeling. Our findings not only offer comprehensive insight into the origins of enantioselectivity in this system but should also aid future development of related photomediated CPA-catalyzed reactions.

PMID:39746148 | DOI:10.1021/jacs.4c13999

J Pediatr Ophthalmol Strabismus. 2024 Dec 30:1-8. doi: 10.3928/01913913-20241121-01. Online ahead of print.

ABSTRACT

PURPOSE: To compare changes of vertical palpebral fissure height after bilateral lateral rectus (BLR) recessions versus unilateral lateral rectus (LR) recession and medial rectus (MR) muscle scleral plication, for treatment of intermittent exotropia.

METHODS: This prospective, comparative, randomized study included 40 patients with intermittent exotropia who were divided into two groups: 20 patients who underwent BLR recessions (BLR recession group) and 20 patients who underwent unilateral LR recession and MR muscle scleral plication (recession-plication group). Eyelid evaluation included measurement of margin reflex distance 1 (MRD1) and margin reflex distance 2 (MRD2) at 1 week, 6 weeks, and 3 months postoperatively. Angle of deviation and any incomitance were also recorded at each visit.

RESULTS: There was no significant statistical difference in eyelid measurements after the surgery between both groups (P = 1.00). There was no significant statistical difference in ocular alignment after the surgery between both groups (P = 1.00). Also, there was no significant statistical difference in lateral incomitance after the surgery between both groups (P = 1.00).

CONCLUSIONS: Both the unilateral recession and plication of horizontal rectus muscles technique and bilateral recession provide comparable surgical results for correction of exotropia without significant palpebral fissures changes or lateral incomitance. [J Pediatr Ophthalmol Strabismus. 20XX;X(X):XXX-XXX.].

PMID:39746118 | DOI:10.3928/01913913-20241121-01

Int J Circumpolar Health. 2025 Dec;84(1):2439122. doi: 10.1080/22423982.2024.2439122. Epub 2025 Jan 2.

ABSTRACT

This study aimed to 1) describe the prevalence of Adverse Childhood Experiences (ACE) in relation to the type of substance used (alcohol or cannabis) among adults seeking treatment for Substance Use Disorder (SUD) in Greenland, and 2) examine whether an association exists between ACE and the type of substance used (alcohol and/or cannabis). The analysis was conducted using register data from individuals receiving SUD treatment in Greenland between 1 June 2020 to 31 December 2022 (N = 1037). The results showed a higher prevalence and a greater variety of ACE among women compared to men. Among men, no significant associations were found between ACE and the substance categories. However, among women, unstable conditions in the childhood home were associated with high use of either alcohol or cannabis. Additionally, high cannabis use was significantly associated with parent(s) with cannabis abuse and physical abuse for women. No cumulative effect of the number of ACE, and any type of substance abuse was found. Growing up with parents with alcohol problems emerged as the most frequently reported ACE for both sexes (reported by 74.6% of women and 62.7% of men).

PMID:39746114 | DOI:10.1080/22423982.2024.2439122

PLoS One. 2025 Jan 2;20(1):e0316397. doi: 10.1371/journal.pone.0316397. eCollection 2025.

ABSTRACT

BACKGROUND: There is increasing acknowledgment of the potential role that diet rich in antioxidants may play in the prevention of anemia. As a significant indicator of antioxidant-rich diet, the relationship between the composite dietary antioxidant index (CDAI) and anemia has not been extensively studied. Therefore, this study aims to explore the association between CDAI and anemia.

METHODS: Utilizing datas from the 2003-2018 National Health and Nutrition Examination Survey (NHANES) database. The CDAI was calculated using six dietary antioxidants, based on two 24-hour dietary recall interviews, serving as comprehensive measure of the intake of these antioxidants. Weighted multivariable logistic regression and restricted cubic spline (RCS) analysis was conducted to investigate the association between CDAI and anemia. Furthermore, subgroup analyses were performed to enhance datas reliability.

RESULTS: A total of 33914 participants were included in the study, among which 3,416 (10.07%) were diagnosed with anemia. The unadjusted model showed negative association between CDAI and anemia (odds ratio [OR]: 0.94; 95% confidence interval [95%CI]: 0.93-0.96; P < 0.001). After adjusting for all covariates, with each increase in CDAI level linked to 3% lower risk of anemia (OR: 0.97; 95%CI: 0.95-0.98; P < 0.001). Moreover, when CDAI was categorized into quartiles, the observed trend persisted (P < 0.001). The RCS analysis revealed linear negative relationship between CDAI and anemia (P for nonlinearity = 0.619). Except for sex, smoking, diabetes and hypertension, no statistically significant interactions were found in any subgroup analysis (P < 0.05 for interaction).

CONCLUSION: Our findings suggest that CDAI levels are inversely related to the prevalence of anemia. Consequently, monitoring individuals with low CDAI scores may facilitate the timely identification of anemia and enhance clinical decision-making.

PMID:39746109 | DOI:10.1371/journal.pone.0316397

PLoS One. 2025 Jan 2;20(1):e0316289. doi: 10.1371/journal.pone.0316289. eCollection 2025.

ABSTRACT

Predicting incident duration and understanding incident types are essential in traffic management for resource optimization and disruption minimization. Precise predictions enable the efficient deployment of response teams and strategic traffic rerouting, leading to reduced congestion and enhanced safety. Furthermore, an in-depth understanding of incident types helps in implementing preventive measures and formulating strategies to alleviate their influence on road networks. In this paper, we present a comprehensive framework for accurately predicting incident duration, with a particular emphasis on the critical role of street conditions and locations as major incident triggers. To demonstrate the effectiveness of our framework, we performed an in-depth case study using a dataset from San Francisco. We introduce a novel feature called “Risk” derived from the Risk Priority Number (RPN) concept, highlighting the significance of the incident location in both incident occurrence and prediction. Additionally, we propose a refined incident categorization through fuzzy clustering methods, delineating a unique policy for identifying boundary clusters that necessitate further modeling and testing under varying scenarios. Each cluster undergoes a Multiple Criteria Decision-Making (MCDM) process to gain deeper insights into their distinctions and provide valuable managerial insights. Finally, we employ both traditional Machine Learning (ML) and Deep Learning (DL) models to perform classification and regression tasks. Specifically, incidents residing in boundary clusters are predicted utilizing the scenarios outlined in this study. Through a rigorous analysis of feature importance using top-performing predictive models, we identify the “Risk” factor as a critical determinant of incident duration. Moreover, variables such as distance, humidity, and hour demonstrate significant influence, further enhancing the predictive power of the proposed model.

PMID:39746103 | DOI:10.1371/journal.pone.0316289

PLoS One. 2025 Jan 2;20(1):e0312316. doi: 10.1371/journal.pone.0312316. eCollection 2025.

ABSTRACT

Most deaths among children under 5 years occur within the first 24 hours of hospital admission from preventable causes such as diarrhea, pneumonia, malaria, and HIV/AIDS. The predictors of these deaths are not yet well documented in our setting. This study aimed to describe the patterns and predictors of these mortalities among children aged 1-59 months at a regional hospital in South Western Uganda. We conducted a prospective cohort study among 208 children aged 1-59 months admitted to Mbarara Regional Referral Hospital. The mortality rate within the first 24 hours was 7.7% (95% CI 4-12) and the median time to death was 7.3(2.62-8.75) hours. Most deaths occurred in infants, with severe pneumonia, severe acute malnutrition, and malaria as leading causes. Factors predicting mortality included admission during the night (AHR: 3.7, 95% CI 1.02-13.53, p-value 0.047) and abnormal neutrophil count(AHR: 3.5, 95% CI 1.10-11.31, p-value 0.034). The study highlights the importance of timely interventions, particularly for infants, and suggests extra monitoring for those admitted at night or with abnormal neutrophil counts.

PMID:39746100 | DOI:10.1371/journal.pone.0312316

PLoS One. 2025 Jan 2;20(1):e0316357. doi: 10.1371/journal.pone.0316357. eCollection 2025.

ABSTRACT

BACKGROUND: Accelerometers are widely adopted for physical activity (PA) measurement. Accelerometry data require pre-processing before entering formal statistical analyses. Many pre-processing criteria may influence PA outcomes and the processed sample, impacting results in subsequent statistical analyses.

AIM: To study the implications of pre-processing criteria for accelerometer data on outputs of interest in physical activity studies.

METHODS: We used the ActiGraph hip-worn accelerometry data from 538 adult Latino participants. We studied four most important domains of pre-processing criteria (wear-time, minimum wear-time, intensity level, and modified bouts). We examined the true sample size in pre-processed data, the moderate-to-vigorous physical activity (MVPA) outcome, and regression coefficients of age and gender predicting MVPA.

RESULTS: Many pre-processing criteria have minimum impact to the output of interest. However, requirements for minimum wear-time can have high influence on subsequent analyses for MVPA. High requirements for wear-time (e.g., minimum of 5 days with more than 12 hours of wear-time per day) lead to weakened statistical efficiency in estimating the relationship between potential predictors and the MVPA outcome. Intensity levels using vector magnitude triaxial counts yielded drastically different results than those using conventional vertical axis counts.

CONCLUSION: Moderate changes in minimum wear-time can yield notably different output data and subsequently influence analyses assessing the impacts of interventions on MVPA behaviors. Processed data using vector magnitude and conventional vertical axis counts are not directly comparable. Sensitivity analyses using alternative pre-processing scenarios are highly recommended to verify the robustness of analyses for accelerometry data.

PMID:39746092 | DOI:10.1371/journal.pone.0316357

JAMA Surg. 2025 Jan 2. doi: 10.1001/jamasurg.2024.5913. Online ahead of print.

ABSTRACT

IMPORTANCE: Increasing evidence supports the oncologic safety of de-escalating axillary surgery for patients with breast cancer after neoadjuvant chemotherapy (NAC).

OBJECTIVE: To evaluate the oncologic outcomes of de-escalating axillary surgery among patients with clinically node (cN)-positive breast cancer and patients whose disease became cN negative after NAC (ycN negative).

DESIGN, SETTING, AND PARTICIPANTS: In the NEOSENTITURK MF-1803 prospective cohort registry trial, patients from 37 centers with cT1-4N1-3M0 disease treated with sentinel lymph node biopsy (SLNB) or targeted axillary dissection (TAD) alone or with ypN-negative or ypN-positive disease after NAC were recruited between February 15, 2019, and January 1, 2023, and evaluated.

EXPOSURE: Treatment with SLNB or TAD after NAC.

MAIN OUTCOMES AND MEASURES: The primary aim of the study was axillary, locoregional, or distant recurrence rates; disease-free survival; and disease-specific survival. Number of axillary lymph nodes removed was also evaluated.

RESULTS: A total of 976 patients (median age, 46 years [range, 21-80 years]) with cT1-4N1-3M0 disease underwent SLNB (n = 620) or TAD alone (n = 356). Most of the cohort had a mapping procedure with blue dye alone (645 [66.1%]) with (n = 177) or without (n = 468) TAD. Overall, no difference was found between patients treated with TAD and patients treated with SLNB in the median number of total lymph nodes removed (TAD, 4 [3-6] vs SLNB, 4 [3-6]; P = .09). Among patients with ypN-positive disease, those who underwent TAD were more likely to have a lower median lymph node ratio (TAD, 0.28 [IQR, 0.20-0.40] vs SLNB, 0.33 [IQR, 0.20-0.50]; P = .03). At a median follow-up of 39 months (IQR, 29-48 months), no significant difference was found in the rates of ipsilateral axillary recurrence (0.3% [1 of 356] vs 0.3% [2 of 620]; P ≥ .99) or locoregional recurrence (0.6% [2 of 356] vs 1.1% [7 of 620]; P = .50) between the TAD and SLNB groups, with an overall locoregional recurrence rate of 0.9% (9 of 976). The initial clinical tumor stage, pathologic complete response, and use of blue dye alone as a mapping procedure were not associated with the outcome. Even though patients with TAD demonstrated an increased disease-free survival rate compared with the SLNB group, this difference did not reach statistical significance (94.9% vs 92.6%; P = .07). Factors associated with decreased 5-year disease-specific survival were cN2-3 axillary stage (cN1, 98.7% vs cN2-3, 96.8%; P = .03) and nonluminal type tumor pathologic characteristics (luminal, 98.9% vs nonluminal, 96.9%; P = .007).

CONCLUSIONS AND RELEVANCE: The short-term results suggest very low rates of axillary and locoregional recurrence in a select group of patients with cN-negative disease after NAC treated with TAD alone or SLNB alone followed by regional nodal irradiation regardless of the SLNB technique or nodal pathology. Whether TAD might provide a clear survival advantage compared with SLNB remains to be proven in studies with longer follow-up.

PMID:39745737 | DOI:10.1001/jamasurg.2024.5913