bluuebunny/crossref_metadata_2025_split huggingface dataset:
Targeting BCL2 with Venetoclax Enhances the Efficacy of the KRASG12D Inhibitor MRTX1133 in Pancreatic Cancer
Authors: Becker Jeffrey H. , Metropulos Anastasia E. , Spaulding Christina , Marinelarena Alejandra M. , Shields Mario A. , Principe Daniel R. , Pham Thao D. , Munshi Hidayatullah G. 
Published: August 2024

Abstract
MRTX1133 is currently being evaluated in patients with pancreatic ductal adenocarcinoma (PDAC) tumors harboring a KRASG12D mutation. Combination strategies have the potential to enhance the efficacy of MRTX1133 to further promote cell death and tumor regression. In this study, we demonstrated that MRTX1133 increased the levels of the proapoptotic protein BIM in PDAC cells and conferred sensitivity to the FDA-approved BCL2 inhibitor venetoclax. Combined treatment with MRTX1133 and venetoclax resulted in cell death and growth suppression in 3D cultures. BIM was required for apoptosis induced by the combination treatment. Consistently, BIM was induced in tumors treated with MRTX1133, and venetoclax enhanced the efficacy of MRTX1133 in vivo. Venetoclax could also resensitize MRTX1133-resistant PDAC cells to MRTX1133 in 3D cultures, and tumors established from resistant cells responded to the combination of MRTX1133 and venetoclax. These results provide a rationale for the clinical testing of MRTX1133 and venetoclax in patients with PDAC.
Significance: The combination of MRTX1133 and the FDA-approved drug venetoclax promotes cancer cell death and tumor regression in pancreatic ductal adenocarcinoma, providing rationale for testing venetoclax with KRASG12D inhibitors in patients with pancreatic cancer.
Integrative Multiomic Profiling of Triple-Negative Breast Cancer for Identifying Suitable Therapies
Authors: Jovanović Bojana , Church Sarah E. , Gorman Kara M. , North Khrystyna , Richardson Edward T. , DiLullo Molly , Attaya Victoria , Kasparian Julie , Mohammed-Abreu Ayesha , Kirkner Gregory , Hughes Melissa E. , Lin Nancy U. , Mittendorf Elizabeth A. , Schnitt Stuart J. , Tolaney Sara M. , Goel Shom 
Published: August 2024

Abstract

Purpose:
Triple-negative breast cancer (TNBC) is a heterogeneous disease that carries the poorest prognosis of all breast cancers. Although novel TNBC therapies in development are frequently targeted toward tumors carrying a specific genomic, transcriptomic, or protein biomarker, it is poorly understood how these biomarkers are correlated.

Experimental Design:
To better understand the molecular features of TNBC and their correlation with one another, we performed multimodal profiling on a cohort of 95 TNBC. Our approach involved quantifying tumor-infiltrating lymphocytes through hematoxylin and eosin staining, assessing the abundance of retinoblastoma, androgen receptor, and PDL1 proteins through IHC, and carrying out transcriptomic profiling using the NanoString BC360 platform, targeted DNA sequencing on a subset of cases, as well as evaluating associations with overall survival.

Results:
Levels of RB1 mRNA and RB proteins are better correlated with markers of retinoblastoma functionality than RB1 mutational status. Luminal androgen receptor tumors clustered into two groups with transcriptomes that cluster with either basal or mesenchymal tumors. Tumors classified as PDL1-positive by the presence of immune or tumor cells showed similar biological characteristics. HER2-low TNBC showed no distinct biological phenotype when compared with HER2-zero. The majority of TNBC were classified as basal or HER2-enriched by PAM50, the latter showing significantly improved overall survival.

Conclusions:
Our study contributes new insights into biomarker utility for identifying suitable TNBC therapies and the intercorrelations between genomic, transcriptomic, protein, and cellular biomarkers. Additionally, our rich data resource can be used by other researchers to explore the interplay between DNA, RNA, and protein biomarkers in TNBC.
Social Risk Profile and Cardiovascular‐Kidney‐Metabolic Syndrome in US Adults
Authors: Li Jingkuo , Lei Lubi , Wang Wei , Ding Wenbo , Yu Yanwu , Pu Boxuan , Peng Yue , Li Yinchu , Zhang Lihua , Guo Yuanlin 
Published: August 2024

Background
Poor cardiovascular‐kidney‐metabolic (CKM) health is associated with premature mortality and excess morbidity in the United States. Adverse social conditions have a prominent impact on cardiometabolic diseases during the life course. We aim to examine the association between social risk profile (SRP) and CKM multimorbidity among US adults.

Methods and Results
We used data from the National Health and Nutrition Examination Survey from 1999 to 2018. The definition of CKM syndrome is the coexistence of subclinical or clinical cardiovascular disease, chronic kidney disease, and metabolic disorders. We classified participants by 4 CKM stages according to the different clinical severity of different forms of CKM syndrome. We calculated the summed number of positive SRP measures, including employed, high‐income level, food secure, high education attainment, private insurance, owning a house, and married, as SRP scores and classified them into 4 levels by quartiles: low (0–2), lower‐middle (3–4), upper‐middle (5–6), and high (7–8). A total of 18 373 US adults, aged 20 to 79 years, were included in our analyses. There were 2567 (9.4%) participants with low SRP score level. Most individual SRP measures and a combined SRP score were associated with CKM stages. Compared with high SRP score level, low SRP level was associated with higher odds of having CKM stage 1 (odds ratio [OR], 1.34 [95% CI, 1.06–1.70]), CKM stage 2 (OR, 2.03 [95% CI, 1.59–2.58]), CKM stage 3 (OR, 5.28 [95% CI, 3.29–8.47]), and CKM stage 4 (OR, 5.97 [95% CI, 4.20–8.49]).

Conclusions
Cumulative social disadvantage, denoted by higher SRP burden, was associated with higher odds of CKM multimorbidity, independent of demographic and lifestyle factors.
Confidence of Financial Markets in a Dictatorship – Portugal 1926–1974
Authors: Tomás Ana , Valério Nuno 
Published: August 2024

Abstract
This paper discusses the confidence of financial markets in the Portuguese public debt during the period of military dictatorship (1926–1933) and authoritarian regime (1933–1974). It concludes that the military dictatorship and the authoritarian regime enjoyed a good relationship with financial markets, except at the beginning, as a consequence of the problems resulting from World War I, and at the very end, as a consequence of the impact of the first oil shock.
Examining ‘STEM Education as Culture’ through an Analysis of Lesson Plans as Cultural Apparatus
Authors: Teo Tang Wee , Mabulo Sherwin John San Buenaventura 
Published: August 2024

Abstract
This article presents findings from the document analysis of science, technology, engineering, and mathematics (STEM) lesson plans written and enacted in Southeast Asian classrooms aimed at providing integrative learning experiences for students. The authors argue that the culture of STEM education is embodied in teacher-designed STEM lesson plans or cultural apparatuses. The authors applied Sewell’s theory of culture to unpack the cultural embodiments (physical and abstract elements) embedded in six STEM lesson plans comprising lesson schedules, worksheets, and handouts. The findings showed that certain categories of culture were more evident in specific components of a STEM lesson package. The article contributes to the relatively nascent literature that, to date, has not closely examined teacher-designed integrated STEM curricula using a cultural lens. The study also has implications for STEM teachers to consider making cultural embodiments and practices more visible during their lesson planning and framing of STEM curriculum.
Altered states of consciousness in Danish healthy volunteers and recreational users of psilocybin and the possible impact of setting and intention: Danish validation of the five-dimensional altered states of consciousness questionnaire
Authors: Hovmand Oliver Rumle , Madsen Martin Korsbak , Fisher Patrick MacDonald , Stenbæk Dea Siggaard 
Published: August 2024

Background: Psychedelic substances reliably induce marked altered states of consciousness (ASC), which may be important for lasting effects and clinical outcomes of psychedelic intervention. Several instruments are available to measure the acute psychedelic experience, of which the Five Dimensional Altered States of Consciousness Questionnaire (5D-ASC) is commonly used. The questionnaire can be scored and analyzed as having five dimensions or 11 subscales, but the two have not been evaluated with comparable factor analysis methods. Methods: The Danish translation of the 5D-ASC was completed by one sample of healthy volunteers receiving psilocybin in a laboratory setting ( N = 47) and one sample of recreative users5D-ASC of psychedelics ( N = 550), who reported retrospectively through an online survey based on their most recent experience with psilocybin. We calculated internal consistency measures of Cronbach’s alpha and McDonald’s omega, conducted a confirmatory factor analysis of the previously suggested factor structures, and tested for possible associations between the 5D-ASC total scores and dose, setting, and intention. For the 11 subscales, we reported omega-sem (composite reliability) using the parameters of the fitted confirmatory factor analyses model. Results: Confirmatory factor analysis showed that the 11 subscales had a good fit to data and showed a better fit compared to the originally proposed five-dimensional solution and good internal consistencies. We further found that the 5D-ASC total scores correlated positively with the dose in the recreative sample. We found no correlations between 5D-ASC total scores and intention or setting. Discussion: We find the Danish 5D-ASC to be a valid tool for measuring ASC among Danish-speaking individuals.
Evaluation of Surface Morphology and Stress Distribution of Orthodontic Mini-implants in Maxilla: A Three-dimensional Finite Element Study
Authors: Keeranthodika Naseem , Nambiar Indu , Kandy Binu Purushothaman Panar , Ashok Amrita , Parambil Muhammed Fairooz Palakkott , Kandoth Aswathi 
Published: August 2024

Objectives: Inaccurate design, insertion or loading of mini-implant may lead to disturbed bone turnover and subsequent implant failure. This study assesses the two commonly used types of implants and their bone stress pattern and determines which type of implant may be more patient-compatible. Method: The samples were categorized into four groups and analyzed by scanning electron microscopy to assess the surface morphology. Stress distribution was estimated using finite element method for which three-dimensional (3D) models of the maxilla and mini-screws were prepared. The implant was then inserted 5 mm from the alveolar crest onto the buccal cortical plate of maxilla between the second premolar and first molar within the platform of Ansys Workbench software. Two loads were applied: 5 Ncm and 2 N. Evaluation of von Mises stresses in the bone was estimated. Results: The study concluded that tapered stainless steel screws exerted greater stress on the bone than titanium screws in both situations. As the diameter increased from 1.3 mm to 1.5 mm, the mini-screw displacement and stress were less. Under 2 N force, the stress was distributed around the head and neck of the mini-implant and the cortical bone. Conclusion: The assessment of von Mises stress distributed around an orthodontic mini-implant under a constant load revealed that stainless steel mini-screws generated more stress than titanium mini-screws. It was observed that the majority of the stress and strain is tolerated by the cortical bone, not the cancellous bone. The diameter of mini-screw is more significant irrespective of material composition.
Skeletal Stem Cell–Derived Exosomes Promote Meniscal Tear Healing and Ameliorate Secondary Osteoarthritis
Authors: Zhang Fang-Xue , Dou Yun , Zhang Bo , Zhang Zhen , Du Ming-Ze , Chien Meng-Han , Du Jing-Ke , Ai Li-Ya , Chen Rao , Jiang Dong 
Published: August 2024

Background: The self-repair ability after meniscal tears is poor, leading to the development of posttraumatic osteoarthritis. Promoting the repair of meniscal injuries remains a great challenge, especially in the avascular region. Hypothesis: Local delivery of skeletal stem cell (SSC)–derived exosomes (SSC-Exos) would promote meniscal healing and prevent secondary osteoarthritis progression. Study Design: Controlled laboratory study. Methods: SSCs were isolated from bone marrow and exosomes were extracted via ultracentrifugation. The cell migration capabilities after incubation with exosomes were validated through in vitro cell culture. Full-thickness longitudinal medial meniscal tears were performed in the avascular region of 40 male Sprague-Dawley rats and 20 male New Zealand White rabbits, which were randomly divided into 2 groups: group treated with phosphate-buffered saline (GCON) and group treated with exosomes (GExosome). The effects of these treatments on meniscal healing and secondary osteoarthritis were evaluated by gross inspection, biomechanical testing, and histological assessment. RNA sequencing of in vitro cell cultures was performed to explore the underlying mechanisms. Results: Exosomes were successfully extracted and identified. These exosomes significantly promoted cell migration capabilities in vitro ( P < .01). The GExosome exhibited greater cell proliferation and tissue regeneration with type 2 collagen secretion, and a significantly higher meniscal repair score than that of the GCON at 8 weeks postoperatively ( P < .05). In contrast to the degenerative changes in both the meniscus and articular cartilage of the GCON, meniscal tissue in the GExosome exhibited restoration of normal morphology with a smooth and glossy white surface and better mechanical strength at 8 weeks after meniscal repair. Both degeneration scores and synovitis scores were significantly higher in the GCON than in the GExosome ( P < .05). Compared with the GCON, the expression of key genes related to cell migration, such as the chemokine family, was enhanced by exosome injection, leading to an upregulation of extracellular matrix expression while downregulating the expression of inflammation-related genes such as CD68 and the matrix metalloproteinase family. Conclusion: The administration of SSC-Exos effectively promoted meniscal healing in the avascular region and ameliorated secondary osteoarthritis. The effect might be attributed to inflammation modulation, promotion of cell migration, and secretion of extracellular matrix components. Clinical Relevance: Injection of SSC-Exos represents a promising therapeutic option for promoting meniscal healing in the avascular region.
Patient Factors Influencing Outcomes at 12-Year Follow-up of Hip Arthroscopy for Femoroacetabular Impingement
Authors: Champagne Gabriel , Dartus Julien , Pelet Stéphane , Matache Bogdan A. , Belzile Etienne L. 
Published: August 2024

Background: Arthroscopic treatment of femoroacetabular impingement has increased in popularity since the early 2000s when it was first described, although only a few midterm follow-up studies have been published. Purpose: To describe the outcomes of patients undergoing hip arthroscopy for femoroacetabular impingement at a mean 12-year follow-up and to determine the risk factors for failure. Study Design: Case-control study; Level of evidence, 3. Methods: The Non-Arthritic Hip Score (NAHS) and a radiographic evaluation were completed preoperatively and at midterm follow-up. Participants were divided into 2 groups according to their clinical evolution. The success group consisted of patients whose NAHS at the final follow-up was above the established Patient Acceptable Symptom State (PASS) threshold of 81.9, whereas patients who underwent a second surgical intervention or did not reach the PASS threshold at final follow-up were assigned to the failure group. These groups were compared to identify preoperative differences in demographic, pathological, and surgical factors. Results: A total of 95 hips were included, after 23 were lost to follow-up (80.5% follow-up). At a mean follow-up of 12.1 years (range, 9.2-16.0 years), 9 hips required total hip arthroplasty (9.5%), 5 required revision hip arthroscopy (5.3%), 29 did not achieve the NAHS PASS threshold (30.5%), and 52 achieved the NAHS PASS threshold (54.7%). The mean NAHS was 82.4 at final follow-up compared with 66.9 preoperatively (mean difference = 15.5; P < .001). Higher mean body mass index (24.9 vs 23.0; P = .030), older age (30.0 vs 27.2; P = .035), and inferior preoperative lateral joint space width (3.9 vs 4.4; P = .019) were associated with inferior prognosis in the failure group versus success group. Osteoarthritis progression was observed in 69.2% of the failure group and in 34.8% of the success group ( P = .082). Labral ossification was observed in 78.3% of all patients, and its lateral projection length was statistically associated with failure ( P = .015). Conclusion: At a mean 12-year follow-up, hip arthroscopy for femoroacetabular impingement led to significant clinical improvement, with 55% PASS achievement. In total, 31% of patients were below the PASS threshold, 5% had revision arthroscopy, and only 9% had conversion to total hip arthroplasty for a 45% global failure rate. Increased body mass index, older age, and smaller preoperative lateral joint space width were significant negative prognostic factors. Postoperative degenerative changes were highly prevalent and demonstrated association with failure.
Synthesis and characterization of novel organoclay-epoxy based flame retardant nanocomposites
Authors: Altaf Muhammad , Ahmed Muhammad Naeem , Iqbal Anila , Khan Arshad Ali 
Published: August 2024

In this study, cost-effective, widely spread, and nontoxic fillers were used to improve the flame retardancy of epoxy nanocomposites. A novel and environmentally benign cation exchange approach was used for the modification of bentonite nanoclay with positively charged L-serine, used to synthesize nanocomposites. Modification of clay was confirmed by using X-ray photoelectron spectroscopy (XPS) and Fourier transform infrared (FT-IR) spectroscopy. X-ray diffraction (XRD) technique proved increase of d-spacing from 12.82 Å to 14.42 Å as a result of cation exchange. Field emission scanning electron microscopy (FE-SEM) and energy-dispersive X-ray spectroscopy (EDS) were used to investigate microstructure of the nanocomposites. Reduction in weight loss, with 28.0 % to 34.0 % increase in char yield of epoxy nanocomposites was determined by the thermogravimetric analysis (TGA). Underwriters laboratories (UL-94) V-0 ratings of nanocomposites indicated improved flame retardancy. Nanofillers significantly reduced the loading of aluminum tri-hydroxide (ATH) and improved the flame retardancy through its synergistic effect.
Vitamin B12 Status in Vegan and Vegetarian Seventh-Day Adventists: A Systematic Review and Meta-Analysis of Serum Levels and Dietary Intake
Authors: Janko Robert K. , Haussmann Irmgard , Patel Ashok 
Published: August 2024

Objective This systematic review and meta-analysis aimed to evaluate the vitamin B12 status and intake of Seventh-day Adventists following a plant-based diet and compare it with omnivore controls to investigate their susceptibility for vitamin B12 deficiency. Data Source Peer-reviewed articles were identified through a comprehensive search in PubMed, Scopus, and Google Scholar databases from inception up to the year 2024 using specific keywords related to vitamin B12 and Seventh-day Adventists. Study Inclusion and Exclusion Criteria Observational studies published in the English language were included if they reported on vitamin B12 status or intake among plant-based Adventists and compared it with omnivore controls who may or may not have been Adventists. Studies that did not present distinguishable results for vegetarian/vegan from omnivore Adventists or only reported on food item intake without specific vitamin B12 data were excluded. Data Extraction Two independent reviewers extracted data on study characteristics, vitamin B12 intake, and serum levels using a customised data extraction form, resolving discrepancies through consultation with a third reviewer. Data Synthesis A meta-analysis was conducted using random-effect models due to anticipated heterogeneity, without any subgroup analysis due to the low number of studies. Sensitivity analysis was performed using the ‘leave-on-out’ method to assess individual study influence on overall effect size and heterogeneity. Results Four studies met inclusion criteria, encompassing 1994 participants. Meta-analysis showed no significant differences in serum vitamin B12 levels (MD: −9.85 pmol/L; 95% CI: −45.64 to 25.94 pmol/L; P = 0.54, I2 = 50%) or daily intake (MD: 3.31 mcg/d; 95% CI: −4.70 to 11.32 mcg/d; P = 0.42, I2 = 90%) between plant-based Adventists and omnivore controls, although there was high heterogeneity between the studies. Conclusion Adventists following a vegan or vegetarian diet did not demonstrate increased risk of vitamin B12 deficiency due to the widespread consumption of fortified foods and supplements. The findings underscore the importance of supplementation and the consumption of fortified foods for maintaining adequate B12 status among vegan or vegetarian Adventists but highlight the need for further studies to confirm these observations in diverse geographical areas.