bluuebunny/crossref_metadata_2025_split huggingface dataset:
α-Mangostin-phytosomes as a plausible nano-vesicular approach for enhancing cytotoxic activity on SKOV-3 ovarian cancer cells
Authors: Alamoudi Abdulmohsin J. , Badr-Eldin Shaimaa M. , Ahmed Osama A. A. , Elbehairi Serag Eldin I. , Alfaifi Mohammad Y. , Asfour Hani Z. , Mohamed Gamal A. , Ibrahim Sabrin R. M. , Abdel-Naim Ashraf B. , Abdallah Hossam M. 
Published: October 2024

Abstract
Background
α-Mangostin is a major xanthone in Garcinia mangostana L. (Clusiaceae) pericarps. It has promising anti-proliferative potential in different cancer cells; however, it has poor oral bioavailability. Phytosomes are used as a novel nano-based drug delivery system. The aim of this research was to enhance the anti-proliferative potency of α-mangostin by formulating it as α-mangostin-phytosome (α-M-PTMs) and assessing its impact on SKOV-3 ovarian cancer cells in comparison to pure α-mangostin.

Results
The size and entrapment efficiency of the proposed formulation were optimized using Box–Behnken statistics. The optimized formula was characterized using transmission electron microscope. The binding of α-mangostin to phospholipids was confirmed using Fourier-transform infrared (FTIR) spectroscopy. The optimized α-mangostin-phytosomes formula exhibited enhanced anti-proliferative activity with reference to raw α-mangostin. This was further substantiated by assessing the cell cycle phases that indicated an accumulation of SKOV-3 cells in the sub-G1 phase. Annexin-V staining revealed enhanced apoptotic activity in α-mangostin-phytosome-treated cells. This was associated with upregulation of CASP3 (Caspase-3), BAX (BCL2 Associated X, Apoptosis Regulator) and TP53 as well as down-regulation of BCL2 mRNA (B-Cell Leukemia/Lymphoma 2). Moreover, our data indicated enhanced ROS (Reactive oxygen species) production, cytochrome-C release, and disturbed MMP (mitochondrial membrane potential).

Conclusion
Encapsulation of α-mangostin in a phytosome nano-formula enhances its anti-proliferative effects in SKOV-3 cells via, at least in part, inducing mitochondrial apoptotic cell death.
Temporal insights into mega-events and waterfront industrial heritage transformation: a case study of Shanghai’s Huangpu River industrial zone
Authors: Wang Kaixuan 
Published: October 2024

AbstractThis research examines the evolution and renewal of Shanghai’s Huangpu River industrial zone after the 2010 Shanghai Expo, with a temporal focus on the profound changes and development philosophies driven by this mega-event. By investigating emblematic case studies along the Huangpu River, such as the transformative 80,000-ton silo, the Shanghai Museum of Contemporary Art, and the Long Museum, this research articulates how mega-events serve as pivotal moments for reimagining and repurposing industrial heritage. In the wake of the 2010 Shanghai Expo, these industrial relics emerged as focal points of urban regeneration, embodying the tensions and synergies between historical preservation and contemporary urban development. This study explores the temporal layers—from the event’s catalytic role to enduring legacies—and reveals how time influences the trajectory of urban spaces and the community’s connection to them. Through this temporal lens, the paper analyses the redevelopment process, assessing how these initiatives have reconfigured the industrial waterfront into a dynamic cultural landscape. The findings offer a dynamic perspective on the temporal dimensions that underpin the redevelopment of industrial heritage sites, providing insights into how such spaces can be continuously activated and symbiotically integrated into the fabric of the city. This paper aims to contribute to a broader understanding of the complexities involved in harnessing industrial heritage for mega-events, with implications for future urban planning and heritage conservation strategies.
A prediction analysis testing if internet-delivered cognitive-behaviour therapy is most suitable for the milder cases of pediatric obsessive-compulsive disorder
Authors: Aspvall Kristina , Mataix-Cols David , Melin Karin , Norlin Lisa , Serlachius Eva , Andersson Erik 
Published: October 2024

Abstract
Background
Common clinical sense would suggest that individuals with milder obsessive-compulsive disorder (OCD) symptoms should be the most suitable for guided internet-delivered cognitive behaviour therapy (CBT), with more intensive forms of treatment reserved for more severe or complex cases.

Results
In this secondary data analysis of a non-inferiority clinical trial comparing internet-delivered CBT with in-person CBT for young people with OCD (N = 152), we found that higher baseline symptom severity predicted worse treatment outcomes in the in-person group but not the internet-delivered CBT group. Additional analyses showed that among individuals with milder symptoms, internet-delivered CBT was associated with worse outcomes than in-person CBT.

Conclusions
If replicated, these results would question the axiom that internet-delivered CBT is most suitable for milder cases.

Trial registration
The original trial was registered at ClinicalTrials.gov ID NCT03263546. Date of registration 2017–08–28.
Three Versus Six Months of Adjuvant Oxaliplatin-Containing Chemotherapy for Patients With Stage III Colorectal Cancer: A Contemporary Real-World Analysis
Authors: Krishnan Tharani , Leung Emily , Solar Vasconcelos Joao Paulo , Lim Howard , Loree Jonathan M. , Davies Janine , Gill Karamjit , Gill Sharlene 
Published: October 2024

PURPOSE
Based on the International Duration Evaluation of Adjuvant Chemotherapy analysis, 3 months of adjuvant chemotherapy with capecitabine and oxaliplatin (CAPOX) is an option for stage III colorectal cancer (colorectal cancer [CRC]), with cost and toxicity benefits. We examined the patterns of uptake of CAPOX versus fluorouracil, leucovorin, and oxaliplatin (FOLFOX) and chemotherapy duration in a contemporary real-world cohort of patients in Canada.

METHODS
The provincial pharmacy database was used to identify patients with resected stage III CRC receiving adjuvant chemotherapy between January 2021 and December 2022. Demographic, tumor, and treatment information was collected and compared.

RESULTS

Of 452 patients, 234 (52%) and 218 (48%) were planned to receive 3 and 6 months of chemotherapy, respectively. Within the 3-month group, 226 (97%) received CAPOX. Within the 6-month group, there was a 51%-49% split between CAPOX and FOLFOX. Age >70 years (
P
= .039), well/moderately differentiated (
P
= .005), and low-risk disease (
P
< .0001) were significantly associated with 3 months. Performance status, ileostomy, or preexisting neuropathy did not affect treatment choice. Of patients planned for 6 months, 29% had low-risk disease, with 52% of these receiving CAPOX. Patients receiving 6 months were more likely to report neuropathy (68
v
36%,
P
< .0001) and to stop oxaliplatin early (54
v
31%,
P
< .0001). The most likely reason for early adjuvant discontinuation was neuropathy in the 6-month group and gastrointestinal toxicity in the 3-month group (
P
< .0001). Irrespective of duration, mean time from consult to starting chemotherapy was longer for FOLFOX versus CAPOX (24
v
19 days,
P
= .007).

CONCLUSION
In this contemporary cohort, 6 months chemotherapy is still being offered to patients with low-risk disease and is associated with more neuropathy. Exploration of patient preferences and resource costs may improve adoption of reduced duration adjuvant CAPOX in stage III CRC.
An NMR-Based Metabolic Signature to Identify Clinically Significant Prostate Cancer in Patients Undergoing Biopsy
Authors: Ladurner Michael , Ameismeier Tobias , Klocker Helmut , Steiner Eberhard , Hauffe Helga , Aigner Gerhard P , Neuwirt Hannes , Böld Tina , Strathmeyer Selina , Heidegger Isabel , Drettwan Diana , Eder Iris E 
Published: October 2024

Abstract

Context
Despite clinical suspicion of prostate cancer (PCa), 20% to 25% of patients exhibit a tumor-negative biopsy result.

Objective
This work aimed to assess the serum metabolic profile of clinically significant (cs) compared to clinically insignificant (ci) PCa or benign (Be) patients.

Methods
A total of 1078 serum samples were analyzed. Nuclear magnetic resonance (NMR) spectroscopy was used to quantify 73 metabolites; random forest was used for the model algorithm.

Results
We identified a 22-metabolite panel, which discriminated csPCa (International Society of Urological Pathology [ISUP] 2-5, n = 328) from ciPCa (ISUP 1, n = 101) and Be patients (negative biopsy, n = 649) with a higher performance when combined with the standard clinical parameters age, prostate-specific antigen (PSA), and percentage free PSA (%fPSA) (area under the curve [AUC] 0.84) than the clinical parameters alone (AUC 0.73). Our study further revealed significant dysregulations of the urea cycle and the choline pathway along with changes in tricarboxylic acid cycle, cholesterol metabolism, and a significant increase of the inflammation marker glycoprotein acetyls B in csPCa patients. In particular, ornithine and dimethylglycine were the 2 most important features to discriminate csPCa from Be + ciPCa with significantly higher ornithine and lower dimethylglycine levels in patients with csPCa (ornithine: 63.7 ± 26.5 µmol/L, dimethylglycine: 12.6 ± 6.3 µmol/L; P &lt; .001) compared to Be + ciPCa patients (ornithine: 50.3 ± 31.6 µmol/L, dimethylglycine: 14.9 ± 7.7 µmol/L).

Conclusion
This study discovered a 22-metabolite panel to discriminate patients with csPCa from Be + ciPCa patients when combined with age, PSA, and %fPSA. It may therefore be used as a supportive biomarker to reduce the number of unnecessary biopsies and also to identify novel therapeutic targets in the future.
Long-Term Glycemic Variability Predicts Adverse Outcomes in Diabetic Heart Failure With Preserved Ejection Fraction
Authors: Hsu Jung-Chi , Yang Yen-Yun , Chuang Shu-Lin , Lin Lian-Yu 
Published: October 2024

Abstract

Context
Previous studies have shown associations between glycemic variability (GV) and cardiovascular outcomes in patients with type 2 diabetes. However, the effect of GV on outcomes in diabetic patients with heart failure with preserved ejection fraction (HFpEF) has not been investigated.

Objective
To investigate the association between increased GV and cardiovascular outcomes in diabetic patients with HFpEF.

Methods
Between 2014 and 2019, we conducted a retrospective cohort analysis using the electronic medical records of a tertiary medical center in Taiwan. Diabetic patients with HFpEF were enrolled. Each individual's coefficient of variability of fasting glucose (FGCV) was determined and the FGCVs were categorized into tertiles. Multivariable Cox regression models and the Kaplan-Meier with log-rank test were used to assess the association between the FGCV and the risk of hospitalization for heart failure (HHF), atrial fibrillation (AF), cardiovascular mortality, and overall mortality.

Results
In a cohort comprising 74 835 individuals diagnosed with diabetes, a subset of 753 patients was identified with HFpEF and measurement of FGCV. The median follow-up duration was 38.1 months. In the model of full adjustment, the third FGCV tertile was statistically significantly associated with an increased risk of HHF compared to the first tertile (hazard ratio [HR] = 1.32; 95% CI, 1.04-1.69; P = .025). Likewise, the highest FGCV tertile was associated with an increased risk of death (HR 1.65; 95% CI, 1.16-2.35; P = .005), whereas it was not associated with increased of AF and cardiovascular mortality. Kaplan-Meier analyses revealed a statistically significant association between FGCV and both HHF and overall mortality (log-rank P = .022 and &lt;.001, respectively).

Conclusion
Our study highlights a significant association between increased GV and a higher incidence of HHF as well as an elevated overall mortality rate in individuals with diabetes and HFpEF.
7530 Monoacylglycerol metabolism in adipose tissue macrophages
Authors: Mooring A , Park M y , Bruno J , Aleman Diaz J O 
Published: October 2024

Abstract
Disclosure: A. Mooring: None. M. Park: None. J. Bruno: None. J.O. Aleman Diaz: None.
White adipose tissue is a heterogeneous organ that is comprised of multiple cell types including adipocytes, nerve cells, endothelial cells and immune cells, each of which are important contributors to adipose tissue homeostasis. Adipose tissue macrophages (ATMs) are key regulators of local and systemic inflammation, adipocyte differentiation and extracellular lipid accumulation. Recent studies evaluating the lipidomic profile of extracellular vesicles (EV) released from adipocytes indicate an association between specific lipid species in EVs and metabolic dysfunction. Individual lipid species influence the crosstalk that occurs between adipocytes and ATMs indicating them as potential molecular messengers. LC-MS analysis performed in our lab has identified monoacylglycerols (MAGs) as the most abundant lipid species in human primary ATMs. However, the role of MAGs in the communication between adipocytes and ATMs remains unclear. To investigate the impact of MAGs on ATMs, we cultured mouse-derived J774.A1 macrophages and treated them with varying concentrations of MAGs (5µM, 50µM, 500µM, 5mM, or 50mM) for 24 hours. We observed significant intracellular lipid accumulation via a targeted LC-MS approach.When MAGs were added to the J774.A1 cell line at a concentration of at least 5mM compared to untreated cells. To further explore this, we employed confocal microscopy to qualitatively assess differences in lipid localization in these cells. We treated an additional cell culture with 50mM of triacylglycerol (TAG) as a control. As anticipated, the cells stored the TAG as lipid droplets. In contrast, cells treated with MAG displayed a dispersed cytosolic storage pattern for the lipid. These findings indicate that the J774.A1 cell line actively stores MAG differently compared to TG. To correlate our cellular findings in human tissues, MALDI imaging was conducted on sections of human visceral adipose tissue. Our in-situ analyses showed spatial anti-correlation between monoglycerides (MAG 20:2, MAG22:2, MAG20:3, MAG 22:3) and triglycerides (TAG 46:9 and TAG 50:8), indicating a distinct location of MAGs within adipose tissue. Our findings provide insights into the accumulation of this neutral lipid within ATMs, as well as its spatial distribution in human tissues. Leveraging these insights may contribute to the development of targeted therapies to mitigate the metabolic complications associated with excess weight.
Presentation: 6/1/2024
7122 Obesity is associated with lower basal state cortisol, and diminished cortisol response to the low dose 1ug ACTH: time to depart from the obesity/pseudo-Cushing myth
Authors: Sofer Yael , Osher Esther , Greenman Yona , Michele Tordjman Karen , Shenkerman Galina , Yaron Marianna , Marcus-Perlman Yonit , Moshe Yaffa , Shaklai Sigal , Limor Rona , abiri shirly , Cantrell Dror , Stern Naftali 
Published: October 2024

Abstract
Disclosure: Y. Sofer: None. E. Osher: None. Y. Greenman: None. K.M. Tordjman: None. G. Shenkerman: None. M. Yaron: None. Y. Marcus-Perlman: None. Y. Moshe: None. S. Shaklai: None. R. Limor: None. S. abiri: None. D. Cantrell: None. N. Stern: None.
Objective: Some clinical resemblance may exist between obesity, particularly abdominal obesity, and Cushing’s syndrome. This has stimulated ongoing interest in the role of cortisol's secretion pattern, control and metabolism in obesity. Goals: To compare basal and dynamic cortisol response to an intravenous bolus dose of 1 ug ACTH in healthy obese versus lean controlsDesign: Total, free and salivary cortisol were tested at the basal state and after a standard challenge with 1 ug ACTH in 60 healthy obese subjects (mean BMI= 39 kg/m2) and 54 healthy lean controls (mean BMI=23 kg/m2). Results: Basal total cortisol was significantly lower in obese as compared to lean subjects [361.56+/-132 vs 414+/- 121 nmol/L; p=0.019]. Additionally, baseline total cortisol and salivary cortisol were inversely related to BMI (r=-0.24, r=-0.27; p&lt;0.05 for both). Baseline total and salivery cortisol were also negatively correlated with waist circumference (r=-0.27, r= -0.34; p&lt;0.05 for both). Upon challenge with ACTH, total and salivary cortisol response were significantly lower in obese than in lean subjects [665.16+/-151.8 vs. 728.64+/- 124.2 nmol/L, p&lt;0.05; 31.66 (19-38.64) vs. 40.05 (31.46-46.64) nmol/L, p&lt;0.05]. Conclusion: Basal as well as peak stimulated cortisol and integrated post-1ug ACTH-stimulated total serum cortisol levels were significantly lower in obese subjects. Obesity is not associated with enhanced basal cortisol or ACTH-stimulated cortisol reserve. Hence, increased serum or salivary cortisol is atypical for uncomplicated obesity.
Presentation: 6/1/2024
6851 Rapidly Increasing Use of Anti-Obesity Medications among Veterans in the Veterans Health Administration (VA)
Authors: Vimalananda Varsha , Qian Shirley , Bolton Rendelle , Hung Anna , Smith Valerie , Maciejewski Matthew 
Published: October 2024

Abstract
Disclosure: V. Vimalananda: None. S. Qian: None. R. Bolton: None. A. Hung: None. V. Smith: None. M. Maciejewski: None.
Introduction: Obesity is a prevalent and costly chronic disease that compromises quality of life; increases risks of cardiometabolic disease, osteoarthritis, and several cancers; and accounts for 28% of U.S. health care costs. Anti-obesity medications (AOMs) may fill the treatment gap given the low uptake of bariatric surgery and limited effectiveness of behavioral interventions, and are guideline-recommended as part of a comprehensive obesity treatment plan. The landscape for obesity treatment has changed with introduction of the highly effective and in-demand glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and dual GLP-1 + GIP receptor agonists (GIP/GLP-1 RAs). Given limited knowledge of use patterns, we describe use of AOMs among patients receiving care in the Veterans Health Administration (VA), which is the largest integrated health system in the United States. Methods: In a retrospective cohort study of VA patients from 7/1/2021-6/30/2023, we examined data from the VHA Corporate Data Warehouse separately for patients on AOMs without and with diagnosed diabetes, since the newer AOMs can be used at lower doses for the diabetes indication. Results: There were 31,106 patients without diabetes and at least one AOM prescription in the two year study period, who were 60% male and 62% White. AOM prescriptions from Year 1 to Year 2 among this group increased 215%. Overall, prescriptions were: semaglutide 34%, liraglutide 18%, orlistat 18%, phentermine/topiramate 14%, bupropion/naltrexone 12%, phentermine 4% and tirzepatide 0.03%. Prescribers were physicians 60%, LIPs 25%, and pharmacists 13%. There were 188,017 patients with diagnosed diabetes and at least one AOM prescription, and they were 92% male and 67% white. AOM prescriptions from Year 1 to Year 2 among this group increased 14% and were primarily (87%) for semaglutide. Prescribers were physicians 63%, licensed independent practitioners (LIPs) 23%, and pharmacists 10%. Conclusions AOM use is increasing in VA across all AOM classes, particularly among patients without diabetes, indicating growing interest in medical treatment of obesity. As AOM use spreads, real-world evidence on weight loss and clinical outcomes is needed among patients like those in VA who tend to be older and less healthy than the highly selected patients included in randomized clinical trials. Data is especially needed to guide practice among patients with obesity and without diabetes, given the dramatic increase in use among that group over the past 2 years.
Presentation: 6/1/2024
7279 Survodutide and Semaglutide Both Induce Weight Loss but Show Different Effects on Food Preference and Dyslipidemia in the Free Choice Diet-induced Obese Hamster Model
Authors: Briand F , Augustin R , Bleymehl K , Zimmermann T , Klöckener T , Klein T 
Published: October 2024

Abstract
Disclosure: F. Briand: Employee; Self; Physiogenix. R. Augustin: Employee; Self; Boehringer Ingelheim. K. Bleymehl: Employee; Self; Boehringer Ingelheim. T. Zimmermann: Employee; Self; Boehringer Ingelheim. T. Klöckener: Employee; Self; Boehringer Ingelheim. T. Klein: Employee; Self; Boehringer Ingelheim.
Introduction: Semaglutide, a GLP-1 receptor agonist, and survodutide, a GCGR/GLP-1R dual agonist, have demonstrated significant weight loss in patients with obesity. To test whether this weight loss is associated with changes in food preference and improvement in dyslipidemia, we evaluated semaglutide and survodutide in the free choice diet-induced obese and dyslipidemic hamster, a model with a human-like lipoprotein metabolism. Methods: Obesity and dyslipidemia were induced with a 20-week free choice diet, which presents hamsters with a choice between control chow diet or high fat/cholesterol diet, and normal water or 10% fructose water. Obese hamsters were then kept on this free choice diet and treated subcutaneously once daily with vehicle, semaglutide 15 nmol/kg or survodutide 15 nmol/kg for 5 weeks. Results: Compared with vehicle, semaglutide and survodutide led to a 17% and 11% body weight reduction, respectively (both p&lt;0.001 vs vehicle). Compared to vehicle, both chow diet and high fat diet intakes were significantly lower during the first week of semaglutide treatment, but then returned to baseline values. However, semaglutide significantly increased normal water intake and reduced fructose-enriched water intake during the whole treatment period (both p&lt;0.001). Survodutide had a different effect, as it did not alter chow diet and normal water intakes, but significantly reduced high fat diet and fructose-enriched water intakes during the 5-week treatment period. Semaglutide and survodutide significantly reduced plasma insulin levels and the HOMA-IR index of insulin resistance (both p&lt;0.01 vs. vehicle). Both semaglutide and survodutide significantly reduced plasma total cholesterol levels by 24% and 41%, respectively (both p&lt;0.001). This hypocholesterolemic effect led to lower HDL-cholesterol levels (-25%, p&lt;0.001) but unchanged LDL-cholesterol levels for hamsters treated with semaglutide. In contrast, in hamsters treated with survodutide, cholesterol lowering was observed in all lipoprotein fractions, including LDL-cholesterol (-39%, p&lt;0.001). Conclusion: Semaglutide and survodutide both induce weight loss and lower HOMA-IR, but have different effects on food preference and dyslipidemia in the obese hamster model; such effects may be attributed to the GCGR agonism of survodutide. These preclinical data highlight the potential metabolic benefits of the GCGR/GLP-1R dual agonist survodutide for the treatment of obesity and related metabolic comorbidities.
Presentation: 6/3/2024