cometadata/datacite-titles-descriptions-related-identifiers huggingface dataset:
DOI: 10.6084/m9.figshare.24449218
title: Supplementary Material for: Safety and Effectiveness of Trastuzumab Biosimilar SB3 in Korean Patients, a Post-Marketing Surveillance Study

description: Introduction: SB3 is a trastuzumab biosimilar approved in Australia, Brazil, Canada, the European Union, the Republic of Korea, Switzerland, and the United States. This real-world study evaluated safety and effectiveness of SB3 as part of the Korean post approval safety management system. Methods: This post-marketing surveillance in Korea included patients in line with approved indications, i.e. patients with early or metastatic breast cancer or metastatic gastric cancer. Safety outcomes were adverse events and adverse drug reactions. Effectiveness outcomes were tumor response and event-free survival. Results: 424 patients were evaluated: 366 patients (86%) with early breast cancer, 53 patients (13%) with metastatic breast cancer, and 5 patients (1%) with metastatic gastric cancer. Among patients with breast cancer, adverse events (mostly mild) and adverse drug reactions were reported by 158 (37.7%) and 57 (13.6%) patients, respectively. Most patients with an AE (141, 75.9%) had no change in treatment schedule. Treatment was temporarily suspended in 14 (8.2%) patients with an AE and completely discontinued in 7 (3.7%). Among patients with early and metastatic breast cancer who were evaluated for efficacy, objective response rates were 82.7% and 38.3%, respectively. Pathological complete response was 64.6% in patients with early breast cancer. Discussion/Conclusion: Safety and efficacy of SB3 demonstrated in this real-world study were comparable with previous studies of reference trastuzumab.
DOI: 10.6084/m9.figshare.24449218.v1
title: Supplementary Material for: Safety and Effectiveness of Trastuzumab Biosimilar SB3 in Korean Patients, a Post-Marketing Surveillance Study

description: Introduction: SB3 is a trastuzumab biosimilar approved in Australia, Brazil, Canada, the European Union, the Republic of Korea, Switzerland, and the United States. This real-world study evaluated safety and effectiveness of SB3 as part of the Korean post approval safety management system. Methods: This post-marketing surveillance in Korea included patients in line with approved indications, i.e. patients with early or metastatic breast cancer or metastatic gastric cancer. Safety outcomes were adverse events and adverse drug reactions. Effectiveness outcomes were tumor response and event-free survival. Results: 424 patients were evaluated: 366 patients (86%) with early breast cancer, 53 patients (13%) with metastatic breast cancer, and 5 patients (1%) with metastatic gastric cancer. Among patients with breast cancer, adverse events (mostly mild) and adverse drug reactions were reported by 158 (37.7%) and 57 (13.6%) patients, respectively. Most patients with an AE (141, 75.9%) had no change in treatment schedule. Treatment was temporarily suspended in 14 (8.2%) patients with an AE and completely discontinued in 7 (3.7%). Among patients with early and metastatic breast cancer who were evaluated for efficacy, objective response rates were 82.7% and 38.3%, respectively. Pathological complete response was 64.6% in patients with early breast cancer. Discussion/Conclusion: Safety and efficacy of SB3 demonstrated in this real-world study were comparable with previous studies of reference trastuzumab.
DOI: 10.6084/m9.figshare.24849561
title: Supplementary Material for: Bone morphogenetic protein-4promotes phenotypic modulation via SMAD-4/MCT-4 axis in vascular smooth muscle cells

description: This study aimed to determine whether bone morphogenetic protein-4 (BMP-4), which increases in response to intimal hyperplasia, promotes phenotype transition in vascular smooth muscle cells (VSMCs). Balloon injury was used to induce intimal hyperplasia in rats. Hematoxylin-eosin staining was used to detect the alteration of vascular structure. Serum levels of BMP-4 and lactate were detected by ELISA. Human aortic smooth muscle cells (HA-SMCs) were cultured. Protein and mRNA expression levels were detected through western blot and real-time PCR. Cell migration was measured by transwell assay. Our data showed that serum concentration of BMP-4 was up-regulated after balloon injury. Treatment with BMP-4 inhibitor DMH1 (4-(6-(4-isopropoxyphenyl)pyrazolo(1,5-a)pyrimidin-3-yl)quinoline) suppressed the abnormal expression of BMP-4 and inhibited the intimal hyperplasia induced by balloon injury. Compared to BMP-4 negative medium, BMP-4 positive medium was associated with higher synthetic VSMCs marker expression levels and lower in contractile gene markers in cultured HA-SMCs. Transfection of monocarboxylic acid transporters-4 (MCT-4) siRNA inhibited the excretion of lactate induced by BMP-4. Our analyses provided evidence that BMP-4 and its regulator Smad-4 are key regulators in MCT-4 mediated lactate excretion. This indicates that BMP-4 stimulates the phenotypic transition of VSMCs via SMAD-4/MCT-4 signaling pathway.
DOI: 10.6084/m9.figshare.24849561.v1
title: Supplementary Material for: Bone morphogenetic protein-4promotes phenotypic modulation via SMAD-4/MCT-4 axis in vascular smooth muscle cells

description: This study aimed to determine whether bone morphogenetic protein-4 (BMP-4), which increases in response to intimal hyperplasia, promotes phenotype transition in vascular smooth muscle cells (VSMCs). Balloon injury was used to induce intimal hyperplasia in rats. Hematoxylin-eosin staining was used to detect the alteration of vascular structure. Serum levels of BMP-4 and lactate were detected by ELISA. Human aortic smooth muscle cells (HA-SMCs) were cultured. Protein and mRNA expression levels were detected through western blot and real-time PCR. Cell migration was measured by transwell assay. Our data showed that serum concentration of BMP-4 was up-regulated after balloon injury. Treatment with BMP-4 inhibitor DMH1 (4-(6-(4-isopropoxyphenyl)pyrazolo(1,5-a)pyrimidin-3-yl)quinoline) suppressed the abnormal expression of BMP-4 and inhibited the intimal hyperplasia induced by balloon injury. Compared to BMP-4 negative medium, BMP-4 positive medium was associated with higher synthetic VSMCs marker expression levels and lower in contractile gene markers in cultured HA-SMCs. Transfection of monocarboxylic acid transporters-4 (MCT-4) siRNA inhibited the excretion of lactate induced by BMP-4. Our analyses provided evidence that BMP-4 and its regulator Smad-4 are key regulators in MCT-4 mediated lactate excretion. This indicates that BMP-4 stimulates the phenotypic transition of VSMCs via SMAD-4/MCT-4 signaling pathway.
DOI: 10.6084/m9.figshare.24624762
title: Supplementary Material for: Estimated prostate volume by semiautomatic segmentation of MRI is more accurately correlated with radical prostatectomy specimen weight than the volume calculated by ellipsoid formula

description: Background: Accurate in-vivo prostate volume (PV) estimation is important for obtaining prostate-specific antigen density (PSAD) and further predicting clinically significant prostate cancer (csPCa). We aimed to evaluate the accuracy of multiparametric magnetic resonance imaging (mpMRI) estimated PV compared to both volume and weight of radical prostatectomy (RP).
Patients and Methods: We identified 310 PCa patients who underwent RP following combined targeted and systematic biopsy in our institution from September 2019 to February 2021. The MRI PV was determined using a semiautomated segmentation algorithm. Formula (prostate weight=(actual weight- 3.8g)/ 1.05 g/ml) was applied and the resulting volume was used in further analysis. RP PV was calculated using the prolate ellipsoid formula (width × height × length × π/6). 
Results: The median PV from MRI, RP and RP weight were 39 ml, 38 ml and 44 ml, respectively. Spearman's rank correlation coefficients (ρ) were 0.841 (MRI PV vs RP weight), 0.758 (RP PV vs RP weight) and 0.707 (MRI PV vs RP PV) (all p&lt;0.001). Decreased correlation between the MRI PV and RP PV was observed in the larger (more than 55ml) prostate. The PSAD derived from MRI PV showed most efficient to detect csPCa in RP specimen (57.9% vs 57.6% vs 45.4%)
Conclusion: MRI PV is correlated better with RP weight than calculated RP PV especially in larger prostate. The high csPCa detection rate in final pathology suggested that PSAD derived from MRI PV can be confidently used in clinical practice.
DOI: 10.6084/m9.figshare.24885009
title: Supplementary Material for: The utility of urinary NGAL as an alternative for serum creatinine to detect acute kidney injury (AKI) in infants exposed to nephrotoxic medications in the NICU

description: Introduction
 Nephrotoxic medication (NTM) exposure is commonly associated with acute kidney injury (AKI) in the neonatal intensive care unit (NICU). Baby NINJA (Nephrotoxic Injury Negated by Just-in-time Action) is a quality improvement program that assesses for AKI in those exposed to NTM with daily serum creatinine (SCr) levels. However, blood draws for SCr are invasive and have clinical disadvantages. Urinary neutrophil gelatinase associated lipocalin (uNGAL) is a promising indicator of AKI. We tested the hypothesis that uNGAL could reliably screen for NTM-AKI in the Baby NINJA program.
Methods
 This two-center prospective study screened 174 NICU subjects, of whom 148 met screening criteria from January 29, 2019, to September 18, 2020. Daily SCr and urine samples were obtained for up to seven days of NTM exposure plus two days after exposure ended or end of AKI. AKI was defined by a SCr rise of 50% from baseline. The highest uNGAL obtained was evaluated to determine its relationship to the diagnosis of AKI. Logistic regression models were used to determine optimal uNGAL cutoffs.
Results
 The negative predictive value of a uNGAL value ≥250 ng/mL was 96.8% (95% CI = 93.3%-100%). Urine NGAL ≥400 ng/mL demonstrated the highest ROC-AUC value of 0.72 with a positive likelihood risk for AKI of 2.76 (1.39-4.13). 
Discussion/Conclusion
 We propose that uNGAL could be used to screen for NTM-AKI and thus replace many blood draws needed in those exposed to NTM. The ideal uNGAL threshold requires further investigation in infants.
DOI: 10.6084/m9.figshare.24631101
title: Supplementary Material for: Co-culture device for in vitro high throughput analysis of cancer associated fibroblast and cancer cell interactions

description: Abstract
Introduction
Cancers in general, and specifically lung cancer, continue to have low patient survival rates when the patient is at an advanced stage when diagnosed. It appears that the local environment, especially fibroblasts and their signaling molecules, tends to induce metastasis, increase cancer cell resistance to treatment, and aid in tumor growth rates. Since 3-D models quickly become too complex and/or expensive, and therefore rarely leave the lab they are developed in, it is interesting to develop a 2-D model that more closely mimics the clustered tumor formation and bulk interaction with a surrounding fibroblast environment. 
Methods
In the present study, we utilize an off-the-shelf stereolithography 3-D printer, standard use well plates, magnets, and metallic beads to create a customizable 2-D co-culture system capable of being analyzed quantitatively with staining and qualitatively with standard fluorescent/brightfield microscopy to determine cancer-fibroblast interactions while also being able to test chemotherapeutic drugs in a high-throughput manner with standard 96-well plates. 
Results
Comparisons from monoculture and co-culture growth rates shows that the presence of fibroblasts allows for significantly increased growth rates for H460 cancer. Additionally, viability of cancer cells can be quantified with simple cell staining methods and morphology and cell-cell interactions can be observed and studied. 
Discussion
The high throughput model demonstrates that boundary condition changes can be observed between cancer cells and fibroblasts based upon the different chemotherapeutics that have been administered.
DOI: 10.6084/m9.figshare.24631101.v1
title: Supplementary Material for: Co-culture device for in vitro high throughput analysis of cancer associated fibroblast and cancer cell interactions

description: Abstract
Introduction
Cancers in general, and specifically lung cancer, continue to have low patient survival rates when the patient is at an advanced stage when diagnosed. It appears that the local environment, especially fibroblasts and their signaling molecules, tends to induce metastasis, increase cancer cell resistance to treatment, and aid in tumor growth rates. Since 3-D models quickly become too complex and/or expensive, and therefore rarely leave the lab they are developed in, it is interesting to develop a 2-D model that more closely mimics the clustered tumor formation and bulk interaction with a surrounding fibroblast environment. 
Methods
In the present study, we utilize an off-the-shelf stereolithography 3-D printer, standard use well plates, magnets, and metallic beads to create a customizable 2-D co-culture system capable of being analyzed quantitatively with staining and qualitatively with standard fluorescent/brightfield microscopy to determine cancer-fibroblast interactions while also being able to test chemotherapeutic drugs in a high-throughput manner with standard 96-well plates. 
Results
Comparisons from monoculture and co-culture growth rates shows that the presence of fibroblasts allows for significantly increased growth rates for H460 cancer. Additionally, viability of cancer cells can be quantified with simple cell staining methods and morphology and cell-cell interactions can be observed and studied. 
Discussion
The high throughput model demonstrates that boundary condition changes can be observed between cancer cells and fibroblasts based upon the different chemotherapeutics that have been administered.
DOI: 10.6084/m9.figshare.24630594
title: Supplementary Material for: Association between BMI and efficacy of SGLT2 inhibitors in patients with heart failure or at risk of heart failure: a meta-analysis based on randomized controlled trials

description: Introduction: This meta-analysis aimed to investigate the effect of SGLT2 inhibitors on the prognosis in patients with heart failure (HF) or at risk of heart failure across different body mass index (BMI).
Methods: We searched PubMed, Embase, Web of Science, and Cochrane Library for all randomized controlled trials (RCTs) comparing SGLT2 inhibitors with placebo in patients with HF or at risk of HF and extracted relevant data up to April 2023 for meta-analysis.
Results: A total of 29,500 patients were enrolled in the selected five studies. The results showed that patients treated with SGLT2 inhibitors had lower heart failure hospitalization (HHF) or cardiovascular (CV) mortality compared to those taking placebo (hazard ratio (HR)=0.73, p&lt;0.001). Patients taking SGLT2 inhibitors also had a lower all-cause mortality rate than those taking placebo (HR=0.85, p=0.017). In BMI subgroup analysis, the HHF rate in the experimental group was lower than that in the control group at BMI ≤24.9 kg/m2, 25.0-29.9 kg/m2, and ≥30.0 kg/m2. There was no significant difference in CV mortality between the two groups at BMI ≤24.9 kg/m2 (HR=0.91, p=0.331) and 25.0-29.9 kg/m2 (HR=0.92, p=0.307). However, when the BMI was ≥30.0 kg/m2, CV mortality with SGLT2 inhibitors was lower than in the control group (HR=0.79, p=0.002). When patients had a BMI ≤24.9 kg/m2 (HR=0.85, p=0.033) and 25.0-29.9 kg/m2 (HR=0.83, p=0.046), the all-cause mortality was lower in the experimental group than in the control group. However, there was no significant difference between the two groups in patients with a BMI ≥30.0 kg/m2 (HR=0.87, p=0.094).
Conclusion: SGLT2 inhibitors improve prognosis in patients with HF or at risk of HF. This effect is affected by BMI.
DOI: 10.6084/m9.figshare.24630594.v1
title: Supplementary Material for: Association between BMI and efficacy of SGLT2 inhibitors in patients with heart failure or at risk of heart failure: a meta-analysis based on randomized controlled trials

description: Introduction: This meta-analysis aimed to investigate the effect of SGLT2 inhibitors on the prognosis in patients with heart failure (HF) or at risk of heart failure across different body mass index (BMI).
Methods: We searched PubMed, Embase, Web of Science, and Cochrane Library for all randomized controlled trials (RCTs) comparing SGLT2 inhibitors with placebo in patients with HF or at risk of HF and extracted relevant data up to April 2023 for meta-analysis.
Results: A total of 29,500 patients were enrolled in the selected five studies. The results showed that patients treated with SGLT2 inhibitors had lower heart failure hospitalization (HHF) or cardiovascular (CV) mortality compared to those taking placebo (hazard ratio (HR)=0.73, p&lt;0.001). Patients taking SGLT2 inhibitors also had a lower all-cause mortality rate than those taking placebo (HR=0.85, p=0.017). In BMI subgroup analysis, the HHF rate in the experimental group was lower than that in the control group at BMI ≤24.9 kg/m2, 25.0-29.9 kg/m2, and ≥30.0 kg/m2. There was no significant difference in CV mortality between the two groups at BMI ≤24.9 kg/m2 (HR=0.91, p=0.331) and 25.0-29.9 kg/m2 (HR=0.92, p=0.307). However, when the BMI was ≥30.0 kg/m2, CV mortality with SGLT2 inhibitors was lower than in the control group (HR=0.79, p=0.002). When patients had a BMI ≤24.9 kg/m2 (HR=0.85, p=0.033) and 25.0-29.9 kg/m2 (HR=0.83, p=0.046), the all-cause mortality was lower in the experimental group than in the control group. However, there was no significant difference between the two groups in patients with a BMI ≥30.0 kg/m2 (HR=0.87, p=0.094).
Conclusion: SGLT2 inhibitors improve prognosis in patients with HF or at risk of HF. This effect is affected by BMI.
DOI: 10.6084/m9.figshare.24550744
title: Supplementary Material for: Transcription factor ATF3 mediating SOCS3 expression aggravates renal ischemia-reperfusion injury by activating mitophagy

description: Introduction: Suppressor of cytokine signaling 3 (SOCS3) is highly expressed in mice with renal ischemia/reperfusion (RI/R) injury and has the potential to regulate mitophagy. On this basis, this study further investigates the possible mechanism via which SOCS3 affects RI/R by regulating mitophagy. 
Method: After establishing a RI/R injury mouse model and a hypoxia/reoxygenation (H/R) cell model, the effects of silenced SOCS3 on injury and mitophagy in the above models were analyzed by ELISA, qRT-PCR, Western blot, pathological sections, CCK-8 assay, flow cytometry and JC-1 assay. Mechanistic studies were carried out with the help of database analysis and binding validation experiments (chromatin immunoprecipitation (ChIP), dual-luciferase reporter assay and Co-Immunoprecipitation (Co-IP)). After the binding target was identified, the regulatory relationship between the target gene and SOCS3 was verified by rescue experiments. 
Result: The large increase in blood urea nitrogen (BUN) and creatinine (Cr) levels verified the success of the RI/R model. SOCS3 expression was up-regulated in RI/R mice. Silenced SOCS3 alleviated kidney damage and mitochondrial abnormalities in RI/R mice, and inhibited mitophagy at the molecular level. Likewise, silenced SOCS3 alleviated H/R-induced cell damage and mitophagy. Finally, activating transcription factor 3 (ATF3) was determined to bind to the promoter of SOCS3, which interacted with insulin-like growth factor 1 receptor (IGF1R). Rescue experiments confirmed the effect of ATF3 on SOCS3 expression and the underlying regulation mechanism. 
Conclusion: ATF3 mediates SOCS3 expression to promote the activation of mitophagy, thereby aggravating renal ischemia-reperfusion injury.
DOI: 10.6084/m9.figshare.24550744.v1
title: Supplementary Material for: Transcription factor ATF3 mediating SOCS3 expression aggravates renal ischemia-reperfusion injury by activating mitophagy

description: Introduction: Suppressor of cytokine signaling 3 (SOCS3) is highly expressed in mice with renal ischemia/reperfusion (RI/R) injury and has the potential to regulate mitophagy. On this basis, this study further investigates the possible mechanism via which SOCS3 affects RI/R by regulating mitophagy. 
Method: After establishing a RI/R injury mouse model and a hypoxia/reoxygenation (H/R) cell model, the effects of silenced SOCS3 on injury and mitophagy in the above models were analyzed by ELISA, qRT-PCR, Western blot, pathological sections, CCK-8 assay, flow cytometry and JC-1 assay. Mechanistic studies were carried out with the help of database analysis and binding validation experiments (chromatin immunoprecipitation (ChIP), dual-luciferase reporter assay and Co-Immunoprecipitation (Co-IP)). After the binding target was identified, the regulatory relationship between the target gene and SOCS3 was verified by rescue experiments. 
Result: The large increase in blood urea nitrogen (BUN) and creatinine (Cr) levels verified the success of the RI/R model. SOCS3 expression was up-regulated in RI/R mice. Silenced SOCS3 alleviated kidney damage and mitochondrial abnormalities in RI/R mice, and inhibited mitophagy at the molecular level. Likewise, silenced SOCS3 alleviated H/R-induced cell damage and mitophagy. Finally, activating transcription factor 3 (ATF3) was determined to bind to the promoter of SOCS3, which interacted with insulin-like growth factor 1 receptor (IGF1R). Rescue experiments confirmed the effect of ATF3 on SOCS3 expression and the underlying regulation mechanism. 
Conclusion: ATF3 mediates SOCS3 expression to promote the activation of mitophagy, thereby aggravating renal ischemia-reperfusion injury.
DOI: 10.6084/m9.figshare.24647778.v1
title: Supplementary Material for: Impact of Bevacizumab Being Skipped due to Adverse Events of Special Interest for Bevacizumab in Patients With Unresectable Hepatocellular Carcinoma Treated With Atezolizumab Plus Bevacizumab: An Exploratory Analysis of the Phase III IMbrave150 study

description: Introduction: The Phase III IMbrave150 study established atezolizumab + bevacizumab as the global standard of care in patients with unresectable hepatocellular carcinoma (HCC). This exploratory analysis examined the impact of bevacizumab interruption due to bevacizumab adverse events of special interest (AESIs). 
Methods: Patients in IMbrave150 who were randomized to atezolizumab + bevacizumab and received treatment for ≥6 months (to reduce immortal time bias) were included in group A-1 if bevacizumab had ever been skipped due to bevacizumab AESIs or to group A-2 otherwise. Efficacy analyses included overall survival (OS) and progression-free survival (PFS) by whether bevacizumab was skipped (group A-1 vs A-2). PFS was evaluated per independent review facility (IRF)–assessed Response Evaluation Criteria in Solid Tumours (RECIST) version 1.1 and HCC-modified RECIST (IRF-HCC mRECIST). Safety was also evaluated. 
Results: Of the 210 patients who received ≥6 months of atezolizumab + bevacizumab, 69 were assigned to group A-1 and 141 to A-2. At data cutoff (August 20, 2020), hazard ratio (HR) for OS was 1.04 (95% CI: 0.64, 1.69) for group A-1 vs A-2. HR for PFS was 1.07 (95% CI: 0.74, 1.55) per IRF-assessed RECIST 1.1 and 1.10 (95% CI: 0.76, 1.59; 15.5 vs 9.7 months) per IRF-HCC mRECIST for group A-1 vs A-2. Safety profiles for atezolizumab and bevacizumab were largely similar between groups. More group A-1 patients had grade 3/4 adverse events. A separate analysis investigating the impact of immortal time bias in patients who received ≥3 months of atezolizumab + bevacizumab supported the appropriateness of the ≥6-month landmark analysis. 
Discussion/Conclusion: Efficacy was similar between patients who skipped bevacizumab due to bevacizumab AESIs and those who did not. Although this comparison was nonrandomized and exploratory, results suggest that skipping bevacizumab due to bevacizumab AESIs did not considerably impact the efficacy and safety of atezolizumab + bevacizumab.
DOI: 10.6084/m9.figshare.24908328
title: Full_dataset.dta for JAMA Open paper 'Prevalence of Short Peer Reviews'

description: Full_dataset for JAMA Open paper 'Prevalence of Short Peer Reviews' (2023)