bluuebunny/crossref_metadata_2025 huggingface dataset:
Association between the atherogenic index of plasma and left ventricular hypertrophy in patients with obstructive sleep apnea: a retrospective cross-sectional study
Authors: Sun Min , Liang Chao , Lin Hui , Chen Zhiyan , Wang Meng , Fang Shijie , Tian Tian , Yang Yujing , Tang Qunzhong , Zhang Erming , Tang Qiang
Published: June 2024

Background

The atherogenic index of plasma (AIP) is a simple and reliable marker of insulin resistance and is closely associated with various cardiovascular diseases (CVDs). However, the relationships between AIP and left ventricular (LV) geometric indicators have not been adequately assessed. This study was carried out to investigate the association between AIP and LV geometric abnormalities in obstructive sleep apnea (OSA) patients.

Methods

This retrospective cross-sectional study included a total of 618 OSA patients (57.3 ± 12.4 years, 73.1% males, BMI 28.1 ± 4.2 kg/m2) who underwent echocardiography. Patients with OSA were diagnosed with clinical symptoms and an apnea-hypopnea index ≥ 5.0. LV hypertrophy (LVH) was defined as left ventricular mass index (LVMIh2.7) ≥ 50.0 g/m2.7 for men and 47.0 g/m2.7 for women. AIP was calculated as log10 (TG/HDL-C).

Results

Compared with the non-LVH group, AIP was significantly higher in the LVH group (0.19 ± 0.29 vs 0.24 ± 0.28, P = 0.024) and the concentric LVH group (0.18 ± 0.29, 0.19 ± 0.30, 0.20 ± 0.26 and 0.29 ± 0.29 in the control, concentric remodeling, eccentric hypertrophy and concentric hypertrophy groups, respectively, P = 0.021). Meanwhile, in the group of patients with the highest AIP tertile, the levels of LVMIh2.7 (42.8 ± 10.5, 43.2 ± 9.3 and 46.1 ± 12.1 in the T1, T2 and T3 groups, respectively, P = 0.003), and the prevalence of LVH (25.2%, 24.0% and 34.6% in the T1, T2 and T3 groups, respectively, P = 0.032) and concentric LVH (10.7%, 9.8% and 20.2% in the T1, T2 and T3 groups, respectively, P = 0.053) were higher compared with those in the other groups. Positive correlations between AIP and LV geometric indicators including the LVMIh2.7, LVMIBSA, LV mass (LVM), diastolic left ventricular inner diameter (LVIDd), diastolic left ventricular posterior wall thickness (PWTd) and diastolic interventricular septal thickness (IVSTd), were revealed according to correlation analysis (P < 0.05). Furthermore, AIP was independently associated with LVMIh2.7 according to multivariate linear regression model (β = 0.125, P = 0.001). Notably, AIP remained independently associated with an elevated risk of LVH [odds ratio (OR) = 1.317 per 1 standard deviation (SD) increment, 95% confidence interval (CI): 1.058 - 1.639, P = 0.014) and concentric LVH (OR = 1.545 per 1 SD increment, 95% CI: 1.173 - 2.035, P = 0.002) after fully adjusting for all confounding risk factors by multivariate logistic regression analyses.

Conclusions

AIP was independently associated with an increased risk of LVH and concentric LVH in OSA patients. Therefore, AIP, as a practical and cost-effective test, might be useful in monitoring hypertrophic remodeling of the heart and improving CVDs risk stratification in clinical management of OSA.
Associations of RBC counts and incidence of DVT in patients with spinal cord injury: a five year observational retrospective study
Authors: Jinlong Zhang , Cheng Wang , Chengqi He
Published: June 2024

Background

The role of red blood cell (RBC) counts as potential independent risk factors for deep vein thrombosis (DVT) in patients with spinal cord injury (SCI) remains uncertain. This study aims to clarify the associations between RBC counts and DVT incidence among this population.

Methods

A retrospective analysis was performed on 576 patients with SCI admitted to the rehabilitation medicine department from January 1, 2017 to December 31, 2021. After exclusions, 319 patients were analyzed, among which 94 cases of DVT were identified.

Results

Mode of injury, D-dimer and anticoagulant therapy were significant covariates (P < 0.05). Age, fibrinogen, D-dimer, anticoagulant therapy and American Spinal Cord Injury Association impairment scale (AIS) grades were associated with RBC counts and DVT incidence (P < 0.05). Adjusting for these factors, a 1.00 × 10^12/L increase in RBC counts correlated with a 45% decrease in DVT incidence (P = 0.042), revealing a “U” shaped relationship with a pivot at 4.56 × 10^12/L (P < 0.05).

Conclusion

RBC counts below 4.56 × 10^12/L serve as a protective factor against DVT, while counts above this threshold pose a risk. These findings could inform the development of DVT prevention strategies for patients with SCI, emphasizing the need for targeted monitoring and management of RBC counts.
Enhanced shifted Jacobi operational matrices of integrals: spectral algorithm for solving some types of ordinary and fractional differential equations
Authors: Ahmed H. M.
Published: June 2024

We provide here a novel approach for solving IVPs in ODEs and MTFDEs numerically by means of a class of MSJPs. Using the SCM, we build OMs for RIs and RLFI for MSJPs as part of our process. These architectures guarantee accurate and efficient numerical computations. We provide theoretical assurances for the efficacy of an algorithm by establishing its convergence and error analysis features. We offer five numerical examples to prove that our method is accurate and applicable. Through these examples, we demonstrate the greater accuracy and efficiency of our approach by comparing our results with previously published findings. Tables and graphs show that the method produces exact and approximate solutions that agree quite well with each other.
Comprehensive transcriptomic analysis unveils macrophage-associated genes for establishing an abdominal aortic aneurysm diagnostic model and molecular therapeutic framework
Authors: Wu Zhen , Yu Weiming , Luo Jie , Shen Guanghui , Cui Zhongqi , Ni Wenxuan , Wang Haiyang
Published: June 2024

Background

Abdominal aortic aneurysm (AAA) is a highly lethal cardiovascular disease. The aim of this research is to identify new biomarkers and therapeutic targets for the treatment of such deadly diseases.

Methods

Single-sample gene set enrichment analysis (ssGSEA) and CIBERSORT algorithms were used to identify distinct immune cell infiltration types between AAA and normal abdominal aortas. Single-cell RNA sequencing data were used to analyse the hallmark genes of AAA-associated macrophage cell subsets. Six macrophage-related hub genes were identified through weighted gene co-expression network analysis (WGCNA) and validated for expression in clinical samples and AAA mouse models. We screened potential therapeutic drugs for AAA through online Connectivity Map databases (CMap). A network-based approach was used to explore the relationships between the candidate genes and transcription factors (TFs), lncRNAs, and miRNAs. Additionally, we also identified hub genes that can effectively identify AAA and atherosclerosis (AS) through a variety of machine learning algorithms.

Results

We obtained six macrophage hub genes (IL-1B, CXCL1, SOCS3, SLC2A3, G0S2, and CCL3) that can effectively diagnose abdominal aortic aneurysm. The ROC curves and decision curve analysis (DCA) were combined to further confirm the good diagnostic efficacy of the hub genes. Further analysis revealed that the expression of the six hub genes mentioned above was significantly increased in AAA patients and mice. We also constructed TF regulatory networks and competing endogenous RNA networks (ceRNA) to reveal potential mechanisms of disease occurrence. We also obtained two key genes (ZNF652 and UBR5) through a variety of machine learning algorithms, which can effectively distinguish abdominal aortic aneurysm and atherosclerosis.

Conclusion

Our findings depict the molecular pharmaceutical network in AAA, providing new ideas for effective diagnosis and treatment of diseases.
Systematic analysis of IGF2BP family members in non-small-cell lung cancer
Authors: Gong Liping , Liu Qin , Jia Ming , Sun Xifeng
Published: June 2024

Background

The insulin-like growth factor-2 mRNA-binding proteins 1, 2, and 3 (IGF2BP1, IGF2BP2, and IGF2BP3) are known to be involved in tumorigenesis, metastasis, prognosis, and cancer immunity in various human cancers, including non-small cell lung cancer (NSCLC). However, the literature on NSCLC largely omits the specific context of lung squamous cell carcinoma (LUSC), an oversight we aim to address.

Methods

Our study evaluated the differential expression of IGF2BP family members in tumors and normal tissues. Meta-analyses were conducted to assess the prognostic value of IGF2BPs in lung adenocarcinoma (LUAD) and LUSC. Additionally, correlations between IGF2BPs and tumor immune cell infiltration, mutation characteristics, chemotherapy sensitivity, and tumor mutation burden (TMB) were investigated. GSEA was utilized to delineate biological processes and pathways associated with IGF2BPs.

Results

IGF2BP2 and IGF2BP3 expression were found to be upregulated in LUSC patients. IGF2BP2 mRNA levels were correlated with cancer immunity in both LUSC and LUAD patients. A higher frequency of gene mutations was observed in different IGF2BP1/2/3 expression groups in LUAD compared to LUSC. Meta-analyses revealed a significant negative correlation between overall survival (OS) and IGF2BP2/3 expression in LUAD patients but not in LUSC patients. GSEA indicated a positive association between VEGF and IGF2BP family genes in LUAD, while matrix metallopeptidase activity was inversely correlated with IGF2BP family genes in LUSC. Several chemotherapy drugs showed significantly lower IC50 values in high IGF2BP expression groups in both LUAD and LUSC.

Conclusion

Our findings indicated that IGF2BPs play different roles in LUAD and LUSC. This divergence highlights the need for tailored therapeutic strategies and prognostic tools, cognizant of the unique molecular profiles of LUAD and LUSC.
Estimating dengue burden among family contacts through cluster investigation around probable cases in 2022 and 2023 in the Central Region, Burkina Faso
Authors: Ouédraogo Jean Claude Romaric Pingdwindé , Ilboudo Sylvain , Bado Prosper , Compaoré Tegwindé Rebeca , Tougma Alix , Nitiéma Mathieu , Zouré Abdou Azaque , Belemnaba Lazare , Ouédraogo Sylvin , Savadogo Léon Gueswendé Blaise
Published: June 2024

Background

In 2023, Burkina Faso experienced the largest dengue epidemic ever in Africa. This study aimed to estimate the prevalence of symptomatic, subclinical, and asymptomatic dengue and determine the associated factors among adult contacts of dengue in the Central Region, Burkina Faso.

Methods

This cross-sectional study included contacts of dengue probable cases through cluster sampling in 2022–2023. These suspected cases that tested positive were identified from the five health facilities (Pissy CMA, Saaba CM, Kossodo CMA, Samandin CM, and Marcoussis CSPS) that reported the highest number of cases in 2021 per district. All participants underwent dengue and malaria rapid diagnostic tests (RDT). Samples positive for non-structural 1 protein antigen (AgNS1) and/or immunoglobulin M (IgM) were tested for serotype detection by reverse transcription polymerase chain reaction (RT-PCR). Binary logistic regression was done to identify the determinants of asymptomatic, subclinical, and symptomatic dengue among contacts of probable dengue cases.

Results

A total of 484 contacts were included, mostly in 2023 (75.2%). Most participants were females (58.6%), residing (24.3%) and passing their daytime (23.1%) in Saaba. The overall prevalence of dengue was estimated at 15.1% [95% confidence interval (CI): 12.0–18.6%], representing cases not seeking care in hospitals. Asymptomatic cases represented 2.9% (95% CI: 1.6–4.8%). Subclinical and symptomatic cases accounted for 6.0% (95% CI: 4.1–8.5%) and 6.2% (95% CI: 4.2–8.7%), respectively. Of the 58 samples tested by RT-PCR, 10 were confirmed for serotype 3 in 2023. Malaria cases were estimated at 5.6% (95% CI: 3.7–8.0%). After adjustment, participants claiming that a virus transmits dengue were likelier to have asymptomatic dengue [adjusted odds ratio (aOR) = 7.1, 95% CI: 2.4–21.0]. From the multivariable analysis, subclinical dengue was statistically associated with being included in the study in 2023 (aOR = 30.2, 95% CI: 2.0–455.5) and spending the daytime at Arrondissement 4 (aOR = 11.5, 95% CI: 1.0–131.0). After adjustment, symptomatic dengue was associated with living less than 50 m away from cultivated land (aOR = 2.8, 95% CI: 1.1–6.9) and living less than 50 m from a stretch of water (aOR = 0.1, 95% CI: 0.0–0.6).

Conclusions

The overall burden of dengue among populations not seeking care in hospitals was quite high, with few asymptomatic cases. Efforts to manage dengue cases should also target non-hospital cases and raise population awareness. The 2023 epidemic could be due to dengue virus (DENV)-3.

Graphical Abstract
A systematic data characteristic understanding framework towards physical-sensor big data challenges
Authors: Ma Zhipeng , Jørgensen Bo Nørregaard , Ma Zheng Grace
Published: June 2024

Big data present new opportunities for modern society while posing challenges for data scientists. Recent advancements in sensor networks and the widespread adoption of the Internet of Things (IoT) have led to the collection of physical-sensor data on an enormous scale. However, significant challenges arise in conducting high-quality data analytics within the realm of big data. To uncover big data challenges and enhance data quality, it is essential to quantitatively unveil data characteristics. Furthermore, the existing studies lack analysis of the specific time-related characteristics of physical-sensor data. Enhancing the efficiency and precision of data analytics through the big data lifecycle requires a comprehensive understanding of data characteristics to address the hidden big data challenges. To fill in the research gap, this paper proposes a systematic data characteristic framework based on a 6Vs model. The framework aims to unveil the data characteristics in terms of data volume, variety, velocity, veracity, value, and variability through a set of statistical indicators. This model improves the objectivity of data characteristic understanding by relying solely on data-driven indicators. The indicators related to time-related characteristics in physical-sensor data are also included for the analysis of temporal aspects in the physical-sensor data. Furthermore, the big data challenges are linked to each dimension of the 6Vs model to gain a quantitative understanding of the data challenges. Finally, a pipeline is developed to implement the proposed framework, and two case studies are conducted to illustrate the process of understanding the physical-sensor data characteristics and making recommendations for data preprocessing to address the big data challenges. The proposed framework is able to analyze the characteristics of all physical-sensor data, therefore, identifying potential challenges in subsequent analytics, and providing recommendations for data preprocessing. Furthermore, the characteristic indicators can be used to analyze other types of big data.
Desktop 3D printed anatomic models for minimally invasive direct coronary artery bypass
Authors: Ravi Prashanth , Burch Michael B. , Giannopoulos Andreas A. , Liu Isabella , Kondor Shayne , Chepelev Leonid L. , Danesi Tommaso H. , Rybicki Frank J. , Panza Antonio
Published: June 2024

Background

Three-dimensional (3D) printing technology has impacted many clinical applications across medicine. However, 3D printing for Minimally Invasive Direct Coronary Artery Bypass (MIDCAB) has not yet been reported in the peer-reviewed literature. The current observational cohort study aimed to evaluate the impact of half scaled (50% scale) 3D printed (3DP) anatomic models in the pre-procedural planning of MIDCAB.

Methods

Retrospective analysis included 12 patients who underwent MIDCAB using 50% scale 3D printing between March and July 2020 (10 males, 2 females). Distances measured from CT scans and 3DP anatomic models were correlated with Operating Room (OR) measurements. The measurements were compared statistically using Tukey’s test. The correspondence between the predicted (3DP & CT) and observed best InterCostal Space (ICS) in the OR was recorded. Likert surveys from the 3D printing registry were provided to the surgeon to assess the utility of the model. The OR time saved by planning the procedure using 3DP anatomic models was estimated subjectively by the cardiothoracic surgeon.

Results

All 12 patients were successfully grafted. The 3DP model predicted the optimal ICS in all cases (100%). The distances measured on the 3DP model corresponded well to the distances measured in the OR. The measurements were significantly different between the CT and 3DP (p < 0.05) as well as CT and OR (p < 0.05) groups, but not between the 3DP and OR group. The Likert responses suggested high clinical utility of 3D printing. The mean subjectively estimated OR time saved was 40 min.

Conclusion

The 50% scaled 3DP anatomic models demonstrated high utility for MIDCAB and saved OR time while being resource efficient. The subjective benefits over routine care that used 3D visualization for surgical planning warrants further investigation.
Glucagon-like peptide-1 (GLP-1) agonist use and weight change among patients with breast cancer.
Authors: Shen Sherry , Liu Bethina , Fanti Chad , Bromberg Maria , Chen Yuan , Chang Cassandra , Iyengar Neil M.
Published: June 2024

10607

Background: Elevated body mass index (BMI) and post-diagnosis weight gain increase the risk of breast cancer recurrence and all-cause mortality. Chemotherapy and endocrine therapy can worsen metabolic dysfunction and are associated with weight gain. GLP-1 agonists mimic the action of endogenous GLP-1 and stimulate insulin secretion, delay gastric emptying, and promote satiety. In addition to diabetes treatment, several of these agents induce substantial (8-15%) weight loss and are indicated for obesity weight management. The efficacy of GLP-1 agonists during or after breast cancer treatment is unclear. Methods: Patients with breast cancer and prescribed a GLP-1 agonist from 2015-2023 with follow-up weight data (pre- and on/post-GLP-1 agonist) were included in this retrospective cohort study. A linear mixed effects model with a random intercept for baseline patient weight was used to assess mean weight change at each available follow-up timepoint. Relative weight change from baseline to approximately 12 months after GLP-1 agonist initiation was also computed and a multivariable linear regression was used to assess the association of baseline covariates with relative weight change. Results: 75 patients were included; median age was 52 (range 27-74), 4 (5%) had carcinoma in situ, 64 (85%) had stage I – III, and 4 (5%) had stage IV breast cancer. 62 (83%) had hormone receptor-positive tumors; 14 (19%) had HER2-positive and 8 (11%) had triple negative tumors. 40 (53%) received an aromatase inhibitor concurrently with GLP-1 agonist whereas 3 (4%) received tamoxifen concurrently. Chemotherapy was administered to 56 (75%), and 44 (59%) received radiation. 59 (79%) had a diagnosis of diabetes. Median time from breast cancer diagnosis to GLP-1 agonist prescription was 4.3 years (range -4.4 to 29.5). Median weight at breast cancer diagnosis was 85 kg (range 52-163), median BMI was 32 kg/m2 (range 20-53). Median weight upon GLP-1 agonist initiation was 90 kg (range 58-151) and median BMI was 34 kg/m2 (range 23-50). Median duration of GLP-1 agonist use was 20 months (range 6-111). At 12 months after GLP-1 agonist initiation, mean relative weight change was -5% (SD 6%). Mean weight change from GLP-1 agonist initiation was -2.8 kg (95% CI -0.9 to -4.7) at 6 months, -4.2 kg (95% CI -2.1 to -6.2) at 12 months, and -6.2 kg (95% CI -3.7 to -8.7) post-GLP-1 agonist treatment. Baseline BMI, concurrent anti-estrogen therapy, duration of GLP-1 agonist therapy, and comorbid diabetes were not associated with relative weight change in multivariate models. Conclusions: The use of GLP-1 agonists in this cohort of patients treated for breast cancer was efficacious and associated with modest (5%) weight loss. Based on this observed activity, prospective trials are warranted.
Association of patient-reported experience of care with cancer clinical trial participation.
Authors: Mollica Michelle , McNeel Timothy S. , Eton David T , Halpern Michael T.
Published: June 2024

11117

Background: Few individuals diagnosed with cancer participate in clinical trials. Patient-reported experience of care (PEC), assessing patients’ perspectives on interactions with healthcare providers and systems, is important in evaluating quality of care. To help identify patient-centered strategies that may enhance trial enrollment, we examined whether PEC may predict enrollment in clinical trials. Methods: This study utilized Surveillance, Epidemiology, and End Results-Consumer Assessment of Healthcare Providers and Systems (SEER-CAHPS) linked data, including SEER registry data, CAHPS PEC surveys, and Medicare claims. Individuals in SEER-CAHPS who were diagnosed with lung cancer 2000-2018 and completed a CAHPS survey ≥6 months following diagnosis were included. The study outcome, clinical trial enrollment after cancer diagnosis, was determined using Medicare claims; among individuals who enrolled in clinical trials, only those completing a CAHPS survey before trial enrollment were included. PEC was assessed using 5 global ratings (Overall Care, Personal Doctor, Specialist, Health Plan, and Prescription Drug Plan) and 6 composite measures (Doctor Communications, Getting Needed Care, Getting Care Quickly, Getting Needed Drugs, Care Coordination, and Customer Service); all were scored 0 (worse PEC) to 10 (best PEC). Associations of trial participation and PEC were assessed using multivariable logistic regression, controlling for age, race/ethnicity, dual Medicaid status, fee-for-service vs Medicare Advantage plan at diagnosis, and physical problems limiting activities, and were weighted to correspond to the overall SEER population. Results: The study included 5,361 individuals diagnosed with lung cancer; 4.8% of the weighted population enrolled in a clinical trial. Patients with higher PEC ratings for their Specialist (odds ratio [OR] for a 1-point higher PEC score 0.86, 95% CI 0.76, 0.98); for their Health Plan (OR 0.87, 95% CI 0.80, 0.96); and for Getting Needed Care (OR 0.89, 95% CI 0.81, 0.98) had significantly (p<0.05) lower oddsof having enrolled in a clinical trial. Among individuals without physical limitations, association of PEC and trial enrollment were similar. Among individuals with physical limitations, higher PEC ratings for Getting Care Quickly were associated with higher odds (OR 1.20, 95% CI 1.03, 1.39) of having enrolled in a trial. Conclusions: In this population, reporting worse PEC in certain domains was significantly associated with increased clinical trial enrollment. This suggests patients less happy with their clinical care may be more likely to enroll in trials, perhaps to receive different types of care and/or from different providers. PEC associations with trial enrollment differ between patients with vs without physical limitations, suggesting different strategies may be effective for increasing trial enrollment among these two sub-groups.
Randomized phase III study comparing suspension or continuation of PD-1 pathway blockade for patients with advanced non-small-cell lung cancer (SAVE study: JCOG1701).
Authors: Goto Yasushi , Mizutani Tomonori , Sekino Yuta , Nomura Shogo , Yanagitani Noriko , Izumi Hiroki , Hosomi Yukio , Fukuhara Tatsuro , Fujita Yuka , Takahashi Toshiaki , Fukuda Haruhiko , Ohe Yuichiro
Published: June 2024

TPS8659

Background: The advent of immune checkpoint inhibitors (ICIs) targeting the PD-1 pathway, including nivolumab, pembrolizumab, and atezolizumab, has significantly improved the efficacy outcomes, namely progression-free survival (PFS) and overall survival (OS), in the treatment of advanced non-small cell lung cancer (NSCLC). This improvement is underscored by the observation that some patients (pts) who responded to ICIs continued to show a response even after discontinuing the treatment. Consequently, cessation of ICIs may not adversely impact OS, while potentially reducing immune-related toxicity and financial burden. Methods: The JCOG1701 is a multi-institutional, two-armed, open-label, randomized phase III trial. The objective of this study is to confirm the non-inferiority of suspension of ICIs to their continuation in patients with advanced or recurrent NSCLC who have shown a positive response to ICIs for 12 months or longer. For patients in the suspension arm who experience disease progression, re-initiation of immune checkpoint inhibitors (ICIs) is conducted. The patients were randomized in a 1:1 ratio to either the continuation or discontinuation arms. Randomization was performed by the minimization method using the institution, histology (squamous vs. non-squamous), and drug/timing parameters (first-line pembrolizumab/atezolizumab vs. second-line atezolizumab vs. second-line nivolumab vs. second-line pembrolizumab vs. combined therapy with chemotherapy) as adjustment factors. The primary endpoint of the trial is OS, while secondary endpoints include PFS, time to treatment failure of strategy, response rate, PFS post resumption of ICIs, and safety. In the periodical blinded monitoring, the pooled Kaplan-Meier curve for OS seemed significantly better than planned. This motivated to change the primary analysis method from hazard ratio to a difference in 6-year restricted mean survival time with a non-inferiority margin of 5.6 months. With one-sided alpha of 5% and power of 70%, the study aimed to enroll 172 patients assuming that 2-year OS is 94% in both arms. As of Jan 2024, 162 patients have been randomized, with full enrollment projected by Nov 2024. The trial is registered in the Japan Registry for Clinical Trials as jRCT1031190032. An ancillary study exploring the predictive and prognostic role of circulating tumor DNA is also planned. The findings of the JCOG1701 will provide data for making more informed treatment decisions in advanced NSCLC, specifically related to the continuation or suspension of ICIs. Clinical trial information: CRB3180009 .
A phase III, open-label, multicenter, randomized controlled trial of tunlametinib versus investigator-selected chemotherapy in patients with advanced NRAS-mutant melanoma who had previously received immunotherapy.
Authors: Wei Xiaoting , Zhang Weizhen , Fang Meiyu , Zou Zhengyun , Chen Jing , Luo Zhiguo , Tian Hongqi , Jia Zhongwei , Guo Jun , Si Lu
Published: June 2024

TPS9606

Background: NRAS-mutant melanoma is an aggressive subtype with worse prognosis. However, no targeted therapy has been approved to date worldwide. Tunlametinib (HL-085) has showed an encouraging efficacy (confirmed ORR:34.8%, mPFS:4.2 months) with a manageable safety profile in phase II pivotal registrational study, which was published in ASCO 2023 annal meeting (NO.:9510). Here, we present the design of phase III randomized controlled study. Methods: This is a multicenter, two-arm, open-label, randomized controlled phase III confirmatory clinical trial to evaluate the efficacy and safety of tunlametinib in comparison with the combination chemotherapy of investigator's choice in advanced NRAS-mutant melanoma patients who had previously received immunotherapy. A total of 165 subjects from about 12 sites in China will be included and randomly assigned to the corresponding treatment group in 2:1 ratio. Two stratification factors before randomization: LDH level and whether have received chemotherapy. The key inclusion criteria included: a) Patients with unresectable stage III or metastatic IV melanoma confirmed by histology or cytology; b) History of immunotherapy failure or could not tolerate immunotherapy; c) Be able to provide NRAS mutation positive test report at baseline and provide sufficient histological specimens for NRAS mutation confirmation by central laboratory. Experimental group subjects will receive continuous administration of tunlametinib 12mg BID, 28 days per cycle. Control group subjects will receive one of the following regimens which according to investigator's choice (paclitaxel plus carboplatin, or temozolomide plus cisplatin, or dacarbazine plus cisplatin) , 28 days per cycle. The two groups will receive continuous therapy until disease progression or intolerable toxicity. The primary endpoint is progression-free survival which assessed by independent radiology review committee. Secondary endpoints included overall survival, objective response rate, disease control rate, duration of response, safety, pharmacokinetics and exposure-response. Exploratory endpoints are to evaluate quality of life between two groups and to development a companion diagnostic kit for NRAS gene mutations detection. This study is currently open for enrollment. Clinical trial information: NCT06008106 .
A phase 3 trial of fixed dose combinations of fianlimab (anti–LAG-3) + cemiplimab (anti–PD-1) versus relatlimab + nivolumab in patients with unresectable or metastatic melanoma.
Authors: Khushalani Nikhil I. , Mani Jayakumar , Booth Jocelyn , Zhang Zoe , Salvati Mark , Lowy Israel , Fury Matthew G. , Lewis Karl , Manvelian Garen , Tawbi Hussein A.
Published: June 2024

TPS9611

Background: Fianlimab (anti–lymphocyte activation gene 3 [LAG-3]) and cemiplimab (anti–programmed cell death-1 [PD-1]) are high-affinity, fully human, immunoglobulin G4 monoclonal antibodies. Concurrent LAG-3 blockade may enhance the efficacy of anti–PD-1 therapies. Relatlimab (anti–LAG-3) + nivolumab (anti–PD-1) monoclonal antibodies demonstrated benefit in progression-free survival (PFS) in advanced melanoma (Mel) patients compared with nivolumab alone in the RELATIVITY-047 study. In a multicohort Phase 1 study (NCT03005782), fianlimab + cemiplimab demonstrated reproducibly high clinical activity (objective response rate [ORR]: 61%, N=98) in three independent cohorts of advanced PD-(L)1–naïve metastatic Mel patients with an acceptable safety profile. Methods: This is a randomized, open-label, multicenter Phase 3 study (NCT06246916) comparing the fixed dose combination (FDC) of fianlimab + cemiplimab to the FDC of relatlimab + nivolumab in patients with unresectable or metastatic Mel. The primary objective is to demonstrate superiority of fianlimab + cemiplimab compared with relatlimab + nivolumab as measured by ORR assessed by blinded independent central review (BICR). This study will be conducted at approximately 80 sites across North America. Key inclusion criteria are: (1) aged ≥18 years; (2) histologically confirmed unresectable stage III or IV (metastatic) Mel; (3) no prior systemic therapy for unresectable or metastatic Mel; patients with adjuvant and/or neoadjuvant systemic therapies are eligible with a treatment-free and disease-free interval of >6 months; (4) measurable disease per Response Evaluation Criteria in Solid Tumors version 1.1; (5) Eastern Cooperative Oncology Group performance status of ≤1; (6) adequate bone marrow, hepatic, and kidney function. Approximately 560 patients will be randomized in a 1:1 ratio to two treatment arms: Arm A: FDC of fianlimab (Dose 1) + cemiplimab (Dose 2) every 3 weeks intravenously (IV); Arm B: FDC of relatlimab 160 mg + nivolumab 480 mg every 4 weeks IV. All patients will be stratified based on metastatic stage (stage III vs M1a–b vs M1c–d), baseline lactate dehydrogenase level (≤ vs > upper limit of normal), and prior adjuvant and/or neoadjuvant systemic therapy. Patients will receive treatment until disease progression, unacceptable toxicity, withdrawal of consent, a study withdrawal criterion is met, or the sponsor terminates the study. The primary endpoint is ORR and key secondary endpoints are PFS and overall survival. Additional secondary endpoints are duration of response, disease control rate, investigator-assessed ORR and PFS, safety, pharmacokinetics, and immunogenicity. Clinical trial information: NCT06246916 .
Associations of Gestational Exposure to Air Pollution With Maternal Vitamin D Levels: A Meta-Analysis
Authors: Binter Anne-Claire , Ghassabian Akhgar , Zou Runyu , El Marroun Hanan , Lertxundi Aitana , Switkowski Karen M , Estarlich Marisa , Rodríguez-Dehli Ana Cristina , Esplugues Ana , Vrijkotte Tanja , Sunyer Jordi , Santa-Marina Loreto , Fernández-Somoano Ana , Polanska Kinga , McEachan Rosemary R C , Oken Emily , Tiemeier Henning , Guxens Mònica
Published: June 2024

Context

Maternal vitamin D level is an important determinant of pregnancy and child health outcomes. Exposure to air pollution is suspected to increase the risk of vitamin D deficiency, but the evidence is scarce.

Objective

We investigated the association between air pollution during pregnancy and maternal vitamin D levels.

Methods

A total of 15 935 pregnant women from 5 birth cohorts in Europe and the United States were included. Averaged concentrations of nitrogen oxides, fine and coarse particles, and composition of fine particles from conception until vitamin D measurement were estimated at participants’ residential addresses using land-use regression or other spatiotemporal models. Cohorts measured vitamin D as 25(OH)D or 25(OH)D3 levels in serum or plasma at early or mid-pregnancy. We defined suboptimal vitamin D levels as levels below 20 ng/mL. We performed logistic regression models for each cohort to estimate the association between air pollution exposure and suboptimal vitamin D levels and pooled cohort-specific estimates in a random-effect meta-analysis. Models were adjusted for sociodemographic and lifestyle characteristics and month of conception.

Results

We found an association between particulate matter (PM)2.5 and higher odds of suboptimal vitamin D levels (ie, below 20 ng/mL) (odds ratio per 5 μg/m3 increase in PM2.5, 1.43; 95% CI: 1.02, 1.99). There was no association between other air pollutant exposure and vitamin D levels.

Conclusion

PM2.5 exposure might contribute to suboptimal levels of vitamin D in pregnancy. Reducing air pollution exposure should be a priority because vitamin D deficiency may adversely influence offspring development.
Effectiveness and Safety of Different Estradiol Regimens in Transgender Females: A Randomized Controlled Trial
Authors: Cortez Samuel , Moog Dominic , Lewis Christopher , Williams Kelley , Herrick Cynthia J , Fields Melanie E , Gray Teddi , Guo Zhaohua , Nicol Ginger , Baranski Thomas
Published: June 2024

Background

A goal of gender-affirming hormone therapy (GAHT) for transgender women is to use estradiol to suppress endogenous production of testosterone. However, the effects of different estradiol regimens and route of administration on testosterone suppression is unknown. This is the first open-label randomized trial comparing different GAHT regimens for optimal estradiol route and dosing.

Objective

To evaluate 1 month and 6 months testosterone suppression <50 ng/dL with pulsed (once- or twice-daily sublingual 17-beta estradiol) and continuous (transdermal 17-beta estradiol) GAHT.

Methods

This study was conducted at an outpatient adult transgender clinic. Thirty-nine transgender women undergoing initiation of GAHT were randomly assigned to receive either once-daily sublingual, twice-daily sublingual, or transdermal 17-beta estradiol. All participants received spironolactone as an antiandrogen. Doses were titrated at monthly intervals to achieve total testosterone suppression <50 ng/dL.

Results

Transdermal 17-beta estradiol resulted in more rapid suppression of total testosterone, lower estrone levels, with no differences in estradiol levels when compared to once-daily and twice-daily sublingual estradiol. Moreover, there was no difference in the mean estradiol dose between the once-daily and twice-daily sublingual 17-beta estradiol group.

Conclusion

Continuous exposure with transdermal 17-beta estradiol suppressed testosterone production more effectively and with lower overall estradiol doses relative to once or twice daily sublingual estradiol. Most transgender women achieved cisgender women testosterone levels within 2 months on 1 or 2 0.1 mg/24 hours estradiol patches. Given no difference between once- or twice-daily sublingual estradiol, pulsed 17-beta estradiol likely provides no benefit for testosterone suppression.
Anti-monument
Authors: Devji Faisal , Sikander Shahzia
Published: June 2024

Shahzia Sikander speaks to Faisal Devji about her shift from painting to sculpture and the meaning of public art in the contemporary United States.
Sacropolitics
Authors: Nugent David , Suhail Adeem
Published: June 2024

Two decades into the twenty-first century, a panoply of formerly separate movements, interests, organizations, and individuals have converged around shared anxieties about the future of life on earth. This article focuses on the implicit logic on which this “cult(ure) of extinction” is based. We refer to this logic as sacropolitics—the politics of mass public sacrifice. We suggest that sacropolitics describes a practical reimagining of the political emergent across the world during periods of acute crises, such as our shared present. Sacropolitics draws on multiple dispersed, decentralized sources and has emerged during a period of great turbulence and acrimony in the public sphere, when the very notion of truth is up for grabs. Despite its ambiguity, sacropolitics offers a range of related, collectively generated intimations or visions of what the future might be.
Moving Beyond Morphometrics and Alignment: Prospective Longitudinal Study on Cognition, Quality of Life, and Diffusion Metrics in Congenital Craniovertebral Junction Anomalies
Authors: Alle Prashanth , Thakar Sumit , Aryan Saritha
Published: June 2024

BACKGROUND AND OBJECTIVES:

Chiari type I malformation (CMI) has been implicated to cause cognitive impairment. Unusual for a craniovertebral junction (CVJ) anomaly, this phenomenon is postulated to be related to microstructural changes across the brain. However, this has not been confirmed in a longitudinal study, in bony CVJ anomalies, or in the context of quality of life (QOL). This study aimed to analyze cognition, QOL, and diffusion tensor imaging (DTI) metrics before and after surgery for congenital CVJ anomalies and evaluate their correlations with conventional clinico-radiological factors.

METHODS:

Fifty-seven patients with congenital CVJ anomalies—CMI, atlantoaxial dislocation (AAD), and basilar invagination (BI)—were evaluated in this prospective longitudinal study over 3 years with a neuropsychological battery, QOL and functional scores, and DTI metrics. A total of 43 patients (23 with CMI; 20 with AAD or BI) with 1-year postsurgical data were included in the final analysis.

RESULTS:

Cognitive dysfunction in one or more domains was noted in 15 (65%) of the patients with CMI and 16 (80%) of the patients with AAD/BI. Memory and visual motor perception were the most-affected domains in both the cohorts. At the 1-year follow-up, the proportion of patients demonstrating an overall cognitive dysfunction did not change significantly (P > .05). All patients demonstrated significant postoperative improvement in functional and QOL scores at follow-up. DTI metrics improved in many regions postoperatively, but did not correlate with functional or cognitive changes (P > .05).

CONCLUSION:

Cognition is affected in a majority of patients with CMI, AAD, or BI. These patients experience good functional and QOL outcomes after surgery but most of them continue to exhibit cognitive impairment. DTI metrics improve after surgery, but do not correlate with cognitive changes. These findings underline the multidimensional nature of the pathology of these anomalies that complicate achieving the concept of a “successful” surgery.
The Specification of a Computational Model of Physical Activity Habit
Authors: Rebar Amanda L. , Lagoa Constantino Manuel , Gardner Benjamin , Conroy David E.
Published: June 2024

The influence of habit on physical activity is computationally modeled as the aggregated influence of past behavioral choices a person makes in a given context. We hypothesize that the influence of habit on behavior can be enhanced through engagement of the target behavior in a particular context or weakened through engagement of alternative behaviors in that context.
Increasing growth sensitivity of Pinus wallichiana to summer season maximum temperature – evidence from central Bhutan Himalaya
Authors: Tshering Chungdu , Thomte Lamginsang , Dukpa Dorji , Shah Santosh K.
Published: June 2024

The impacts of global warming are pervasive across different forest biomes and are most pro­nounced in high mountain ecosystems such as the Himalayas. This study examines the growth response of Blue pine (Pinus wallichiana) to climate from Bumthang district in the central Bhutan Himalaya. Tree radial growth parameters (ring width index and basal area increment) were correlated with monthly and daily climate. Temporal changes in significant climate response were assessed using running correlations. Irrespective of tree growth parameters or temporal resolution of climatic variables, growth-climate re­sponse revealed maximum temperature during summer as the most significant climatic factor regulating the growth of P. wallichiana in central Bhutan. The strength and stability of the climate response improved when using daily climate, which is not restricted by non-biological calendar months. Around the turn of the 21st century, we observed a rapid rise in radial growth. Over the last ~30 years, blue pine from central Bhutan has benefited from warming summer season maximum temperatures. This study highlights the importance of considering daily climate variables for more accurate assessments of tree growth responses to climate. These findings have significant implications for understanding the impact of climate change on forests in the Himalayan region.
Ο ρόλος των κοινωνικών υπηρεσιών στις διαδικασίες κοινωνικού αποκλεισμού των μεταναστριών θυμάτων σεξουαλικής εκμετάλλευσης στην Ελλάδα
Authors: Τσάκαλου Χριστίνα
Published: June 2024

Η διδακτορική διατριβή που ακολουθεί, έχει σαν στόχο να διερευνήσει τον ρόλο των κοινωνικών υπηρεσιών στις διαδικασίες κοινωνικού αποκλεισμού των μεταναστριών θυμάτων σεξουαλικής εκμετάλλευσης στην Ελλάδα. Κεντρικό κοινωνικό φαινόμενο στην έρευνα που διεξήχθη, είναι το φαινόμενο της σεξουαλικής εκμετάλλευσης των γυναικών, δηλαδή το τράφικινγκ. Εξετάζεται το φαινόμενο του τράφικινγκ, μέσα από το λόγο των φορέων και τις αντιλήψεις τους σε σχέση με τον κοινωνικό αποκλεισμό των θυμάτων Τα ερωτήματα που τίθενται θέτουν στο ερευνητικό στόχαστρο την λειτουργία και το ρόλο των κοινωνικών υπηρεσιών, οργανισμών και κατ’ επέκταση υπαλλήλων τους, που έρχονται σε άμεση επαφή με το φαινόμενο και τις προεκτάσεις του όσον αφορά την αντιμετώπισή του. Η διδακτορική διατριβή εμπεριέχει συμπληρωματικά ερευνητικά πεδία όπως αυτά της μελέτης του κοινωνικού αποκλεισμού, των ανθρώπινων δικαιωμάτων, της μετανάστευσης, της ευρύτερης λειτουργίας της κοινωνικής πολιτικής και των υπηρεσιών και τέλος των έμφυλων διαχωρισμών.Αφορμή για την διερεύνηση όλων των παραπάνω υπήρξε το γεγονός ότι λίγες κοινωνιολογικές έρευνες ασχολούνται με το φαινόμενο του τράφικινγκ, μέσα από την σκοπιά της παροχής κοινωνικών υπηρεσιών προς τις γυναίκες θύματα. Η ανάλυση επικεντρώνεται σε αυτό ακριβώς το σημείο, στην αντιμετώπιση του φαινομένου και στη νοηματοδότησή του, από τους αρμόδιους φορείς και υπηρεσίες. Η ερμηνεία των παραπάνω βασίζεται σε δύο στάδια. Το πρώτο στάδιο αφορά στην καταγραφή των πραγματικών πρακτικών αντιμετώπισης του φαινομένου, όπως περιγράφεται από τους συνεντευξιαζόμενους και το δεύτερο στάδιο αφορά στην ερμηνεία και νοηματοδότηση πτυχών του φαινομένου από τους ίδιους. Είναι σημαντικό να αποσαφηνιστεί ότι το κατά πόσο η ερμηνεία αυτή επηρεάζει τα θύματα, είναι ορατό μόνο από την πλευρά των κοινωνικών υπηρεσιών και όχι από τα ίδια τα θύματα. Η μεθοδολογία της έρευνας προτάσσει ως βασικά εργαλεία, την ημιδομημένη συνέντευξη για τον υπό διερεύνηση πληθυσμό των κοινωνικών υπηρεσιών.Η μελέτη αναδεικνύει τις διαδικασίες κοινωνικού αποκλεισμού στις οποίες συνεχίζουν να υπόκεινται οι γυναίκες αφότου έχουν απευθυνθεί σε αρμόδιες κοινωνικές υπηρεσίες αντιμετώπισης του φαινομένου, καθώς και τα ποιοτικά χαρακτηριστικά εκείνα που δίνουν ερμηνεία και αντίστοιχη πρακτική στο φαινόμενο. Στην Ελλάδα παρατηρείται ότι οι προσπάθειες που γίνονται, σχεδιάζονται σε μια γραμμή διαχείρισης των προβλημάτων που καθορίζουν το φαινόμενο καθώς και διαχείριση των ίδιων των θυμάτων, παρά σε μια ολιστική προσέγγιση αντιμετώπισης του. Ως εκ τούτου, οι διαδικασίες κοινωνικού αποκλεισμού των γυναικών θυμάτων σεξουαλικής εκμετάλλευσης αντί να αναχαιτίζονται σημαντικά, φαίνεται να ενισχύονται ή/και να οδηγούν σε μια ανακύκλωση αρνητικών προτύπων διαβίωσης και κοινωνικοποίησης.
Kodeks wyborczy do natychmiastowej korekty! Czego nie zmieniono przed wyborami z 2023 r. i jakie to miało konsekwencje?
Authors: Michalak Bartłomiej
Published: June 2024

15 października 2023 r. odbyły się w Polsce wybory parlamentarne połączone z referendum ogólnokrajowym. Jeszcze przed wyborami wielu ekspertów wskazywało na konieczność przeprowadzenia niezbędnych zmian w Kodeksie wyborczym. Do najważniejszych należały: likwidacja nierówności głosów w niektórych okręgach wyborczych do Sejmu oraz przywrócenie głosowania korespondencyjnego dla Polaków przebywających za granicą. Niestety polski ustawodawca zmian tych nie wprowadził. Celem tego artykułu będzie znalezienie odpowiedzi na pytania, jaki to miało wpływ na przebieg i ostateczne wyniki wyborów oraz jak przeciwdziałać podobnym zagrożeniom w przyszłości.
Myśl polityczna a filozofia i teologia polityki
Authors: Szlachta Bogdan
Published: June 2024

Wobec wielości znaczeń nadawanych terminom „myśl polityczna”, „filozofia” i „teologia polityczna” konieczne jest ustalenie możliwych relacji między nimi. Tekst przynosi taką próbę, opartą na sugestii, że w pierwszej kolejności należy zdać sobie sprawę z różnych sensów nadawanych polityce (pojmowanej jako wiedza lub praktyka) i polityczności (określanej przez poszukiwanie wspólnego rozwiązania, a może nawet dobra, albo przez zmagania różnych aktorów czy graczy politycznych o narzucenie rozwiązań chroniących czyjeś partykularne interesy). Historyczne tło wywodu zawiera odniesienia do ujęć dawnych, nawet starożytnych, zasadniczo jednak ma ono walor wprowadzający, unaoczniający złożoność analizowanych zagadnień.
Zaczęło się od Kopernika… Wspomnienia z pracy w Towarzystwie Miłośników Torunia
Authors: Iwaniszewska Cecylia
Published: June 2024

Artykuł zawiera wspomnienia z pracy w Zarządzie ToMiTo w latach 1967–2021. Przypomniano w nim sylwetki dawnych działaczy Towarzystwa, stopniowo zastępowanych przez młodszą generację, głównie historyków z Uniwersytetu Mikołaja Kopernika w Toruniu. Omówiono różnorodne rodzaje aktywności Towarzystwa: działalność wydawniczą; organizację imprez i konkursów; różne formy pracy z młodzieżą; współpracę z władzami miasta w zakresie nazewnictwa ulic; opiekę nad cmentarzami; inicjowanie budowy pomników; przyznawanie medalu „Złote Astrolabium”.
25 lat działalności krótkofalowców w Towarzystwie Miłośników Torunia
Authors: Thomas Mariusz
Published: June 2024

Prezentowany artykuł poświęcony jest 25-letniej współpracy toruńskich krótkofalowców (radioamatorów) z Towarzystwem Miłośników Torunia (ToMiTo). W 1998 r. przyjęła ona formę sekcji krótkofalowców ToMiTo, której zadaniem było promowanie na falach eteruwalorów historycznych, kulturowych, przyrodniczych, naukowych i turystycznych pięknego Torunia. Stanowi on fragment opracowania, które ze względu na obszerność i wielowątkowość tematu oraz potrzebę zobrazowania i wizualizacji specyfiki działalności radioamatorskiej (programy dyplomowe, eventy, radioamatorskie stacje okolicznościowe, praca terenowa, okolicznościowe karty QSL, zawody krajowe i międzynarodowe, wystawy) krótkofalowców działających w ramach ToMiTo znacznie przekracza objętość i możliwości edycyjne „Rocznika Toruńskiego”.