bluuebunny/crossref_metadata_2025 huggingface dataset:
Testing Causality in Scientific Modelling Software
Authors: Clark Andrew G. , Foster Michael , Prifling Benedikt , Walkinshaw Neil , Hierons Robert M. , Schmidt Volker , Turner Robert D.
Published: July 2023

From simulating galaxy formation to viral transmission in a pandemic, scientific models play a pivotal role in developing scientific theories and supporting government policy decisions that affect us all. Given these critical applications, a poor modelling assumption or bug could have far-reaching consequences. However, scientific models possess several properties that make them notoriously difficult to test, including a complex input space, long execution times, and non-determinism, rendering existing testing techniques impractical. In fields such as epidemiology, where researchers seek answers to challenging causal questions, a statistical methodology known as Causal inference has addressed similar problems, enabling the inference of causal conclusions from noisy, biased, and sparse data instead of costly experiments. This article introduces the causal testing framework: a framework that uses causal inference techniques to establish causal effects from existing data, enabling users to conduct software testing activities concerning the effect of a change, such as metamorphic testing,
a posteriori
. We present three case studies covering real-world scientific models, demonstrating how the causal testing framework can infer metamorphic test outcomes from reused, confounded test data to provide an efficient solution for testing scientific modelling software.
DSMC Evaluation Stages: Fostering Robust and Safe Behavior in Deep Reinforcement Learning – Extended Version
Authors: Gros Timo P. , Groß Joschka , Höller Daniel , Hoffmann Jörg , Klauck Michaela , Meerkamp Hendrik , Müller Nicola J. , Schaller Lukas , Wolf Verena
Published: July 2023

Neural networks (NN) are gaining importance in sequential decision-making. Deep reinforcement learning (DRL), in particular, is extremely successful in learning action policies in complex and dynamic environments. Despite this success, however, DRL technology is not without its failures, especially in safety-critical applications: (i) the training objective maximizes
average
rewards, which may disregard rare but critical situations and hence lack local robustness; (ii) optimization objectives targeting safety typically yield degenerated reward structures, which, for DRL to work, must be replaced with proxy objectives. Here, we introduce a methodology that can help to address both deficiencies. We incorporate
evaluation stages
(ES) into DRL, leveraging recent work on deep statistical model checking (DSMC), which verifies NN policies in Markov decision processes. Our ES apply DSMC at regular intervals to determine state space regions with weak performance. We adapt the subsequent DRL training priorities based on the outcome, (i) focusing DRL on critical situations and (ii) allowing to foster arbitrary objectives.

We run case studies on two benchmarks. One of them is the Racetrack, an abstraction of autonomous driving that requires navigating a map without crashing into a wall. The other is MiniGrid, a widely used benchmark in the AI community. Our results show that DSMC-based ES can significantly improve both (i) and (ii).
Assessing the Impact of Music Recommendation Diversity on Listeners: A Longitudinal Study
Authors: Porcaro Lorenzo , Gómez Emilia , Castillo Carlos
Published: July 2023

We present the results of a 12-week longitudinal user study wherein the participants, 110 subjects from Southern Europe, received on a daily basis Electronic Music (EM) diversified recommendations. By analyzing their explicit and implicit feedback, we show that exposure to specific levels of music recommendation diversity may be responsible for long-term impacts on listeners’ attitudes. In particular, we highlight the function of diversity in increasing the openness in listening to EM, a music genre not particularly known or liked by the participants previous to their participation in the study. Moreover, we demonstrate that recommendations may help listeners in removing positive and negative attachments towards EM, deconstructing pre-existing implicit associations but also stereotypes associated with this music. In addition, our results show the significant influence that recommendation diversity has in generating curiosity in listeners.
Electrochemistry of Neodymium in an Equimolar NaCl-KCl Melt without and with Addition of Fluoride Ions
Authors: Kuznetsov S. A. , Popova A. V. , Stulov Yu. V. , Markovich S. I.
Published: July 2023

The paper presents the results of neodymium electrochemical behavior in chloride and chloride-fluoride melts. It was shown that the process of neodymium electroreduction in the NaCl-KCl-NdCl3 melt proceeds in two stages. By diagnostic criteria of voltammetry it was established that the discharge process of Nd(III) to Nd(II) at a sweep rate in the range of 0.6 ≤ ν ≤ 1.0 V s−1 is not complicated by disproportionation reaction. In this study diffusion coefficients, activation energy of diffusion for Nd(III) chloride complexes and standard rate constants of charge transfer for the Nd(III)/Nd(II) redox couple in the NaCl-KCl melt were determined. The nature of the working electrode on the standard rate constants of charge transfer for the Nd(III)/Nd(II) redox couple has been studied by cyclic voltammetry and electrochemical impedance spectroscopy. The formal redox potentials E

*

Nd(III)/Nd(II) in the NaCl-KCl melt were obtained from the cyclic voltammetry data. It was shown that the addition of fluorine anions into the NaCl-KCl-NdCl3 melt leads to stabilization of the higher oxidation state of neodymium in chloride-fluoride melts and the intermediate oxidation state Nd(II) does not exist in these melts.
Sensory prediction error drives subconscious motor learning outside of the laboratory
Authors: Albert Scott T. , Blaum Emily C. , Blustein Daniel H.
Published: July 2023

Implicit and explicit learning systems have been detected using simple, constrained movements inside the laboratory. How these systems impact movements during complex whole body, skill-based tasks has not been established. Here, we demonstrate that sensory prediction errors significantly impact how a person updates their movements, replicating findings from the laboratory in an unconstrained ball-rolling task. This real-world validation is an important step toward explaining how subconscious learning helps humans execute common motor skills in dynamic environments.
Large-field-of-view scanning electron microscopy of the paraventricular nucleus of the hypothalamus during diet-induced obesity
Authors: Arestakesyan Hovhannes , Blackmore Katherine , Smith Hannah C. , Popratiloff Anastas , Young Colin N.
Published: July 2023

Paraventricular nucleus of the hypothalamus (PVN) alterations are linked to obesity-related conditions, but limited knowledge exists about neuroanatomical changes in this region. A large-field-of-view backscatter scanning electron microscopy (bSEM) method was used, which allowed the identification of up to 40 PVN neurons in individual samples. During obesity in mice, bSEM revealed changes in PVN neuronal nucleoplasm, possibly indicating chromatin clustering. This microscopy advancement offers valuable insights into neuroanatomy in both healthy and disease conditions.
A Comparative Study of Static VAR Systems for ImprovingVoltage Stability in Expansion of Mining Projects with Gearless Motor Drives
Authors: Olabarrieta Rubio J. L. , Eguia Lopez P. , Torres Iglesias E. , Etxegarai Madina A.
Published: July 2023

In the next decade, the demand for copper is expected to grow by 25%, posing a challenge for mining facilities to increase their production by opening new mines or upgrading existing ones. To optimize the electrical infrastructure of mining facilities, the integration of flexible AC transmission systems (FACTSs) can be instrumental in mitigating voltage stability issues that may arise during the installation of new gearless motor drives (GMDs). The purpose of this paper is to conduct a comparative analysis of the dynamic performance of static VAR systems (SVSs) as a means of enhancing voltage stability in mining expansion projects, particularly in the context of the integration of new GMDs into the system. This paper presents a case study of an existing three crushing-line mine configuration that has been upgraded with two new GMD systems. The primary contribution of this research is a comprehensive methodology designed to enhance the stability of a mining system through the integration of an SVS, which includes the sizing of the SVS system, an analysis of costs, as well as a determination of the required installation surface and optimal placement of the SVS within the system. The simulation results conclusively demonstrate the effectiveness of the SVS systems in reducing the voltage drop by 2% upon activation of new GMDs, as well as mitigating the adverse impact of transient disturbances on the system. Specifically, the first oscillation voltage peak value is improved by 3.5%, following a three-phase short circuit of 1 second duration, while overvoltage is reduced by 1% in response to sudden load changes. When compared with the system without an installed SVS, these findings highlight the significant advantages and benefits of integrating SVSs into mining operations.
A Switched-Capacitor-Based 7-Level Self-Balancing High-Gain Inverter Employing a Single DC Source
Authors: Gopal Yatindra , Panda Kaibalya Prasad , Kumari Akanksha , Rosas-Caro Julio C.
Published: July 2023

This paper discloses a novel switched capacitor (SC)-based 7-level inverter with a single DC source. The proposed inverter has the ability to self-balancing the voltage of the capacitor without using a closed-loop voltage balancing circuit. Two capacitors are equally charged by the input source owing to the series-parallel charging and discharging continuously in a full cycle. The proposed 7-level SC inverter requires less number of switches, driver diodes, and capacitors and a lower number of semiconductor switches than most recently developed topologies. Furthermore, four out of the eight switches operate at the fundamental frequency, which simplifies the control scheme. A fundamental frequency switching scheme is used to control the output of the inverter. The self-balancing and voltage-boosting features of the proposed structure are validated on MATLAB/software platform and verified experimentally.
Orofacial Pain with Cardiac Origin of Coronary Artery Disease: A Case Report and Literature Review
Authors: Choi Eunhye , Lee Yeon-Hee , Park Hee-Kyung
Published: July 2023

When diagnosing orofacial pain, clinicians should also consider non-odontogenic origin and systemic diseases as possible etiological factors, along with odontogenic origin. This case report aimed to provide information for early detection of orofacial pain of cardiac origin by dentists, when pain due to coronary artery disease is the only presenting symptom. A 60-year-old male patient with unexplained isolated bilateral jaw pain that had persisted for the past 5 years was referred to a dentist by an anesthesiologist who suspected temporomandibular joint disorder. In oral examination, no specific pathological changes were observed in the oral cavity, including teeth, surrounding alveolar bone, and buccal mucosa. Magnetic resonance imaging and conventional radiography showed no pathological destruction or abnormalities of bone and soft tissue in the temporomandibular joint region. However, pain was precipitated by ordinary daily activities, and the pain alleviating factor was rest. Eventually, the patient was referred to a cardiologist for further evaluation since his pain was induced by physical activity. Coronary artery disease (CAD) was diagnosed using coronary computed tomography angiography, and the pain was considered to be angina pectoris. Percutaneous coronary intervention was successfully done for the patient, after which his orofacial symptoms disappeared. To conclude, isolated craniofacial pain of cardiac origin may lead to patients seeking dental care or visiting orofacial pain clinics. In these settings, dentists and orofacial pain specialists may contribute to the diagnosis of CAD and refer patients for cardiac evaluation and appropriate management.
Microbiological Assessment of Groundnut (Arachis hypogaea L.) Sold for Consumption in Ghana
Authors: Madilo Felix Kwashie , Glover Richard L. K. , Islam Md. Nazrul , Roy Nitai , Letsyo Emmanuel
Published: July 2023

The postharvest processes of groundnuts often become sources of microbial contamination leading to infections and intoxication. Hence, this study examined the microbial pathogens contaminating groundnuts after harvesting. About 50 samples were randomly collected from four major groundnut-producing towns: Bolgatanga, Chiana, Navrongo, and Bongo, all in the Upper East Region of Northern Ghana, and microbiologically examined using Analytical Profile Index (API® 20E). The results revealed that samples from Bolgatanga were the most contaminated, while Chiana has the least contaminated samples. Several species of bacterial genera such as Staphylococcus, Proteus, Escherichia, Bacillus, and Micrococcus, and fungal genera including Aspergillus, Fusarium, Rhizopus, Mucor, Saccharomyces, and Eurotium were isolated as the main microbial pathogens contaminating the produce. Navrongo and Bolgatanga recorded the highest rate of bacterial species for unshelled (29.5%) and shelled (30.4%) groundnuts, respectively, while Bongo and Bolgatanga registered the highest rate of fungal species under unshelled (32.8%) and shelled (32.6%) groundnuts, respectively. Due to the high levels of microbial contamination of most of the samples and the kind of microbial species involved, proper hygiene standards must be adopted during the postharvest handling of the shelled and unshelled groundnuts.
Supplementary Table 6 from Relationship between ABO Blood Group Alleles and Pancreatic Cancer Is Modulated by Secretor (FUT2) Genotype, but Not Lewis Antigen (FUT3) Genotype
Authors: Kim Jihye , Yuan Chen , Amundadottir Laufey T. , Wolpin Brian M. , Klein Alison P. , Risch Harvey A. , Kraft Peter
Published: July 2023

Table S6 presents joint analysis results of secretor status and Lewis antigen in the relationship with pancreatic cancer risk, stratified by O and non-O blood groups.
Supplementary Table 3 from Relationship between ABO Blood Group Alleles and Pancreatic Cancer Is Modulated by Secretor (FUT2) Genotype, but Not Lewis Antigen (FUT3) Genotype
Authors: Kim Jihye , Yuan Chen , Amundadottir Laufey T. , Wolpin Brian M. , Klein Alison P. , Risch Harvey A. , Kraft Peter
Published: July 2023

Table S3 presents adjusted associations of ABO blood group alleles and pancreatic cancer risk, stratified by secretor status and cohorts, and interactions between ABO blood group alleles and secretor status.
Supplemental Figure 4 from Elevated EVL Methylation Level in the Normal Colon Mucosa Is a Potential Risk Biomarker for Developing Recurrent Adenomas
Authors: Yu Ming , Carter Kelly T. , Baker Kelsey K. , Redman Mary W. , Wang Ting , Vickers Kathy , Li Christopher I. , Cohen Stacey A. , Krane Mukta , Ose Jennifer , Gigic Biljana , Figueiredo Jane C. , Toriola Adetunji T. , Siegel Erin M. , Shibata David , Schneider Martin , Ulrich Cornelia M. , Dzubinski Lynda A. , Schoen Robert E. , Grady William M.
Published: July 2023

Supplemental Figure 4: Methylation levels of normal colon for patients with no history of adenoma or cancer after initial amongst those at least 4 years of follow-up (left group) and levels for patients with an adenoma or colorectal cancer detected after initial colonoscopy (middle group). Patients without an adenoma or colorectal cancer and less than 4 years of follow-up (right group) were not included in the analyses for Comparison Set 3. %mEVL=percentage of DNA that is methylated at the EVL locus assayed.
Supplemental Figure 3 from Elevated EVL Methylation Level in the Normal Colon Mucosa Is a Potential Risk Biomarker for Developing Recurrent Adenomas
Authors: Yu Ming , Carter Kelly T. , Baker Kelsey K. , Redman Mary W. , Wang Ting , Vickers Kathy , Li Christopher I. , Cohen Stacey A. , Krane Mukta , Ose Jennifer , Gigic Biljana , Figueiredo Jane C. , Toriola Adetunji T. , Siegel Erin M. , Shibata David , Schneider Martin , Ulrich Cornelia M. , Dzubinski Lynda A. , Schoen Robert E. , Grady William M.
Published: July 2023

Supplemental Figure 3: EVL methylation levels of normal colon for patients with no history of adenoma or cancer after initial colonoscopy (left group) and for levels patients with an adenoma or colorectal cancer detected after initial (middle group). Patients with no follow-up colonoscopies (right group) were not included in the analyses for Comparison Set 2. %mEVL=percentage of DNA that is methylated at the EVL locus assayed.
Supplementary Table 1 from Relationship between ABO Blood Group Alleles and Pancreatic Cancer Is Modulated by Secretor (FUT2) Genotype, but Not Lewis Antigen (FUT3) Genotype
Authors: Kim Jihye , Yuan Chen , Amundadottir Laufey T. , Wolpin Brian M. , Klein Alison P. , Risch Harvey A. , Kraft Peter
Published: July 2023

Table S1 presents the haplotype and genotype frequencies of ABO blood alleles, secretor status, and Lewis antigen groups.
Supplementary Table S4 from Development of a Breast Cancer Risk Prediction Model Incorporating Polygenic Risk Scores and Nongenetic Risk Factors for Korean Women
Authors: Choi Jihye , Ha Tae-Woong , Choi Hye-Mi , Lee Han-Byoel , Shin Hee-Chul , Chung Woosung , Han Wonshik
Published: July 2023

Association between PRS38_ASN+PRS190_EB and breast cancer risks in different age groups
Supplementary Table S2 from Development of a Breast Cancer Risk Prediction Model Incorporating Polygenic Risk Scores and Nongenetic Risk Factors for Korean Women
Authors: Choi Jihye , Ha Tae-Woong , Choi Hye-Mi , Lee Han-Byoel , Shin Hee-Chul , Chung Woosung , Han Wonshik
Published: July 2023

Weights used for linear combinations of multiple PRS
Supplementary Figure S2 from Genetic Susceptibility to Nonalcoholic Fatty Liver Disease and Risk for Pancreatic Cancer: Mendelian Randomization
Authors: King Sontoria D. , Veliginti Swathi , Brouwers Martijn C.G.J. , Ren Zhewen , Zheng Wei , Setiawan Veronica W. , Wilkens Lynne R. , Shu Xiao-Ou , Arslan Alan A. , Beane Freeman Laura E. , Bracci Paige M. , Canzian Federico , Du Mengmeng , Gallinger Steven J. , Giles Graham G. , Goodman Phyllis J. , Haiman Christopher A. , Kogevinas Manolis , Kooperberg Charles , LeMarchand Loic , Neale Rachel E. , Visvanathan Kala , White Emily , Albanes Demetrius , Andreotti Gabriella , Babic Ana , Berndt Sonja I. , Brais Lauren K. , Brennan Paul , Buring Julie E. , Rabe Kari G. , Bamlet William R. , Chanock Stephen J. , Fuchs Charles S. , Gaziano J. Michael , Giovannucci Edward L. , Hackert Thilo , Hassan Manal M. , Katzke Verena , Kurtz Robert C. , Lee I.-Min , Malats Núria , Murphy Neil , Oberg Ann L. , Orlow Irene , Porta Miquel , Real Francisco X. , Rothman Nathaniel , Sesso Howard D. , Silverman Debra T. , Thompson Ian M. , Wactawski-Wende Jean , Wang Xiaoliang , Wentzensen Nicolas , Yu Herbert , Zeleniuch-Jacquotte Anne , Yu Kai , Wolpin Brian M. , Duell Eric J. , Li Donghui , Hung Rayjean J. , Perdomo Sandra , McCullough Marjorie L. , Freedman Neal D. , Patel Alpa V. , Peters Ulrike , Riboli Elio , Sund Malin , Tjønneland Anne , Zhong Jun , Van Den Eeden Stephen K. , Kraft Peter , Risch Harvey A. , Amundadottir Laufey T. , Klein Alison P. , Stolzenberg-Solomon Rachael Z. , Antwi Samuel O.
Published: July 2023

Supplementary Figure S2 shows forest plot for minimally adjusted model for PanC4 sample
Supplementary Figure S4 from Development of a Breast Cancer Risk Prediction Model Incorporating Polygenic Risk Scores and Nongenetic Risk Factors for Korean Women
Authors: Choi Jihye , Ha Tae-Woong , Choi Hye-Mi , Lee Han-Byoel , Shin Hee-Chul , Chung Woosung , Han Wonshik
Published: July 2023

The absolute risk was estimated using different combinations of PRS and NGRF risk levels. PRS was classified into three risk groups according to percentile distributions (0-20%: low, 20-80%: mid, 80-100%: high). NGRF score was classified into two groups divided at median (0-50%: low, 50-100%: high). The dotted lines represent the average risks. (A) Lifetime absolute risk (B) 5-year absolute risk
Supplementary Figure S1 from Development of a Breast Cancer Risk Prediction Model Incorporating Polygenic Risk Scores and Nongenetic Risk Factors for Korean Women
Authors: Choi Jihye , Ha Tae-Woong , Choi Hye-Mi , Lee Han-Byoel , Shin Hee-Chul , Chung Woosung , Han Wonshik
Published: July 2023

Distribution of PRS38_ASN+PRS190_EB among participants with (case) and without breast cancer (control).
Supplementary Table 1 from Diabetes and Prostate Cancer Outcomes in Men with Nonmetastatic Castration-Resistant Prostate Cancer: Results from the SEARCH Cohort
Authors: Sergeyev Andrei , Gu Lin , De Hoedt Amanda M. , Amling Christopher L. , Aronson William J. , Cooperberg Matthew R. , Kane Christopher J. , Klaassen Zachary , Terris Martha K. , Guerrios-Rivera Lourdes , Freedland Stephen J. , Csizmadi Ilona
Published: July 2023

Supplementary Table 1. Demographic and disease characteristics of patients with and without biopsy grade groups
Data from Associations of Dietary Patterns with Colorectal Adenomas in the Prostate, Lung, Colorectal, and Ovarian Cancer Cohort
Authors: Nepal Sushma , Aslani Zahra , Shi Ni , Tabung Fred K.
Published: July 2023

AbstractBackground:
Most colorectal cancers arise from adenomas, and although insulinemic and inflammatory dietary patterns have been associated with colorectal cancer risk, these dietary patterns have not been studied in relation to adenoma risk.
Methods:
Using data from 21,192 participants in the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer screening cohort, we calculated the Empirical Dietary Index for Hyperinsulinemia (EDIH), Empirical Dietary Inflammatory Pattern (EDIP), and overall dietary quality measured via the Healthy Eating Index (HEI-2015), from food frequency questionnaires (FFQ). In multivariable-adjusted logistic regression, we investigated associations of these dietary indices with adenoma (any adenoma, advanced adenoma, n = 19,493) and recurrent adenoma (n = 1,699).
Results:
EDIH was not associated with adenoma or advanced adenoma but was marginally associated with recurrent adenoma. The OR (95% CI) comparing highest (lowest insulinemic) versus lowest (most hyperinsulinemic) quintiles was 0.76 (0.55–1.05) after multivariable adjustment including BMI. EDIP and HEI-2015 were not associated with any of the three outcomes.
Conclusions:
In the PLCO cohort, we did not observe substantial associations between dietary patterns and risk of colorectal adenomas.
Impact:
Pending confirmation in larger prospective studies, our findings suggest that these dietary patterns may not substantially affect colorectal cancer risk via the adenoma–carcinoma sequence.
Data from Elevated EVL Methylation Level in the Normal Colon Mucosa Is a Potential Risk Biomarker for Developing Recurrent Adenomas
Authors: Yu Ming , Carter Kelly T. , Baker Kelsey K. , Redman Mary W. , Wang Ting , Vickers Kathy , Li Christopher I. , Cohen Stacey A. , Krane Mukta , Ose Jennifer , Gigic Biljana , Figueiredo Jane C. , Toriola Adetunji T. , Siegel Erin M. , Shibata David , Schneider Martin , Ulrich Cornelia M. , Dzubinski Lynda A. , Schoen Robert E. , Grady William M.
Published: July 2023

AbstractBackground:
Individuals with adenomatous colorectal polyps undergo repeated colonoscopy surveillance to identify and remove metachronous adenomas. However, many patients with adenomas do not develop recurrent adenomas. Better methods to evaluate who benefits from increased surveillance are needed. We evaluated the use of altered EVL methylation as a potential biomarker for risk of recurrent adenomas.
Methods:
Patients with ≥1 colonoscopy had EVL methylation (mEVL) measured with an ultra-accurate methylation-specific droplet digital PCR assay on normal colon mucosa. The association between EVL methylation levels and adenoma or colorectal cancer was evaluated using three case/control definitions in three models: unadjusted (model 1), adjusting for baseline characteristics (model 2), and an adjusted model excluding patients with colorectal cancer at baseline (model 3).
Results:
Between 2001 and 2020, 136 patients were included; 74 healthy patients and 62 patients with a history of colorectal cancer. Older age, never smoking, and baseline colorectal cancer were associated with higher levels of mEVL (P ≤ 0.05). Each log base 10 difference in mEVL was associated with an increased risk of adenoma(s) or cancer at/after baseline for model 1 [OR, 2.64; 95% confidence interval (CI), 1.09–6.36], and adenoma(s) or cancer after baseline for models 1 (OR, 2.01; 95% CI, 1.04–3.90) and model 2 (OR, 3.17; 95% CI, 1.30–7.72).
Conclusions:
Our results suggest that EVL methylation level detected in the normal colon mucosa has the potential to be a biomarker for monitoring the risk for recurrent adenomas.
Impact:
These findings support the potential utility of EVL methylation for improving the accuracy for assigning risk for recurrent colorectal adenomas and cancer.
Data from Diabetes and Prostate Cancer Outcomes in Men with Nonmetastatic Castration-Resistant Prostate Cancer: Results from the SEARCH Cohort
Authors: Sergeyev Andrei , Gu Lin , De Hoedt Amanda M. , Amling Christopher L. , Aronson William J. , Cooperberg Matthew R. , Kane Christopher J. , Klaassen Zachary , Terris Martha K. , Guerrios-Rivera Lourdes , Freedland Stephen J. , Csizmadi Ilona
Published: July 2023

AbstractBackground:
The prognosis of diabetic men with advanced prostate cancer is poorly understood and understudied. Hence, we studied associations between diabetes and progression to metastases, prostate cancer–specific mortality (PCSM) and all-cause mortality (ACM) in men with nonmetastatic castration-resistant prostate cancer (nmCRPC).
Methods:
Data from men diagnosed with nmCRPC between 2000 and 2017 at 8 Veterans Affairs Health Care Centers were analyzed using Cox regression to determine HRs and 95% confidence intervals (CI) for associations between diabetes and outcomes. Men with diabetes were classified according to: (i) ICD-9/10 codes only, (ii) two HbA1c values > 6.4% (missing ICD-9/10 codes), and (iii) all diabetic men [(i) and (ii) combined].
Results:
Of 976 men (median age: 76 years), 304 (31%) had diabetes at nmCRPC diagnosis, of whom 51% had ICD-9/10 codes. During a median follow-up of 6.5 years, 613 men were diagnosed with metastases, and 482 PCSM and 741 ACM events occurred. In multivariable-adjusted models, ICD-9/10 code-identified diabetes was inversely associated with PCSM (HR, 0.67; 95% CI, 0.48–0.92) while diabetes identified by high HbA1c values (no ICD-9/10 codes) was associated with an increase in ACM (HR, 1.41; 95% CI, 1.16–1.72). Duration of diabetes, prior to CRPC diagnosis was inversely associated with PCSM among men identified by ICD-9/10 codes and/or HbA1c values (HR, 0.93; 95% CI, 0.88–0.98).
Conclusions:
In men with late-stage prostate cancer, ICD-9/10 ‘code-identified’ diabetes is associated with better overall survival than ‘undiagnosed’ diabetes identified by high HbA1c values only.
Impact:
Our data suggest that better diabetes detection and management may improve survival in late-stage prostate cancer.
Supplementary Fig. 2 from An Open-label Phase I Study of GDC-0927 in Postmenopausal Women with Locally Advanced or Metastatic Estrogen Receptor–Positive Breast Cancer
Authors: Chandarlapaty Sarat , Dickler Maura N. , Perez Fidalgo Jose Alejandro , Villanueva-Vázquez Rafael , Giltnane Jennifer , Gates Mary , Chang Ching-Wei , Cheeti Sravanthi , Fredrickson Jill , Wang Xiaojing , Collier Ann , Moore Heather M. , Metcalfe Ciara , Lauchle Jennifer , Humke Eric W. , Bardia Aditya
Published: July 2023

Supplementary Fig. S2. The PGR z-score for six patients analyzed in Fig. 4.
Supplementary Table 2 from Targeting the ATF6-Mediated ER Stress Response and Autophagy Blocks Integrin-Driven Prostate Cancer Progression
Authors: Macke Amanda J. , Pachikov Artem N. , Divita Taylor E. , Morris Mary E. , LaGrange Chad A. , Holzapfel Melissa S. , Kubyshkin Anatoly V. , Zyablitskaya Evgeniya Y. , Makalish Tatiana P. , Eremenko Sergey N. , Qiu Haowen , Riethoven Jean-Jack M. , Hemstreet George P. , Petrosyan Armen
Published: July 2023

Supplementary Table 2. Combinations of siRNAs and shRNAs used for knockdown experiments.
Supplementary Movies Description from Targeting the ATF6-Mediated ER Stress Response and Autophagy Blocks Integrin-Driven Prostate Cancer Progression
Authors: Macke Amanda J. , Pachikov Artem N. , Divita Taylor E. , Morris Mary E. , LaGrange Chad A. , Holzapfel Melissa S. , Kubyshkin Anatoly V. , Zyablitskaya Evgeniya Y. , Makalish Tatiana P. , Eremenko Sergey N. , Qiu Haowen , Riethoven Jean-Jack M. , Hemstreet George P. , Petrosyan Armen
Published: July 2023

Supplemental Movie 1
PC-3 cell treated with water, stained for Golgi (GRASP65, green) and MGAT3 (red). Surfaces were reconstructed by Imaris.
Supplemental Movie 2
PC-3 cell treated with HCQ, stained for Golgi (GRASP65, green) and MGAT3 (red). Surfaces were reconstructed by Imaris.
Supplemental Movie 3
PC-3 cell treated with water, stained for Integrin αv (red), Gal-3 (green), EEA1 (magenta). Areas of 3-color colocalization are highlighted with white. Surfaces were reconstructed by Imaris.
Supplemental Movie 4
PC-3 cell treated with HCQ, stained for Integrin αv (red), Gal-3 (green), EEA1 (magenta). Areas of 3-color colocalization are highlighted with white. Surfaces were reconstructed by Imaris.
Supplementary Figure 7 from Targeting the ATF6-Mediated ER Stress Response and Autophagy Blocks Integrin-Driven Prostate Cancer Progression
Authors: Macke Amanda J. , Pachikov Artem N. , Divita Taylor E. , Morris Mary E. , LaGrange Chad A. , Holzapfel Melissa S. , Kubyshkin Anatoly V. , Zyablitskaya Evgeniya Y. , Makalish Tatiana P. , Eremenko Sergey N. , Qiu Haowen , Riethoven Jean-Jack M. , Hemstreet George P. , Petrosyan Armen
Published: July 2023

Figure S7. (A, B) Alcohol dehydrogenase (ADH1A) and Aldehyde dehydrogenase (ALDH2) W-B of the lysate of PC-3 (A) and DU145 (B) cells. Asterisks indicate the bands corresponding to the appropriate proteins.
Supplementary Figure 4 from Targeting the ATF6-Mediated ER Stress Response and Autophagy Blocks Integrin-Driven Prostate Cancer Progression
Authors: Macke Amanda J. , Pachikov Artem N. , Divita Taylor E. , Morris Mary E. , LaGrange Chad A. , Holzapfel Melissa S. , Kubyshkin Anatoly V. , Zyablitskaya Evgeniya Y. , Makalish Tatiana P. , Eremenko Sergey N. , Qiu Haowen , Riethoven Jean-Jack M. , Hemstreet George P. , Petrosyan Armen
Published: July 2023

Figure S4. (A) Representative images of Golgi in DU145 cells treated with 60 µM HCQ for 72 h and stained by GM130 (green); bars, 20 µm. (B) Quantification of Golgi spots per cell in samples from A. Unpaired t test; **p<0.01, mean ± SD; n represents a number of cells counted. (C) Representative images of Golgi in DU145 cells treated with control or ATF6α siRNAs and stained by GM130 (green); bars, 20 µm. (D) Quantification of Golgi spots per cell in samples from C. Unpaired t test; ***p<0.001, mean ± SD; n represents number of cells counted. (E) ATF6 W-B of the lysates of DU145 cells transfected with control or ATF6α siRNAs; β-actin is a loading control. (F) Representative images of Golgi in PC-3 cells treated with control or ATG5 siRNAs and stained by GM130 (green); bars, 20 µm. (G) Quantification of Golgi spots per cell in samples from F. Unpaired t test; ****p<0.0001, mean ± SD; n represents number of cells counted. (H) ATG5 W-B of the lysates of PC-3 cells transfected with control or ATG5 siRNAs; γ-tubulin is a loading control. (I) Representative images of Golgi in DU145 cells treated with control or ATG5 siRNAs and stained by GM130 (green); bars, 20 µm. (J) Quantification of Golgi spots per cell in samples from I. Unpaired t test; ****p<0.0001, mean ± SD; n represents number of cells counted. (K) ATG5 W-B of the lysates of DU145 cells transfected with control or ATG5 siRNAs; γ-tubulin is a loading control. (L) Representative images of Golgi in PC-3 cells treated with Bafilomycin A1 (10 µM for 72 h) or appropriate amount of DMSO and stained by GM130 (green); bars, 20 µm. (M) Quantification of Golgi spots per cell in samples from L. Unpaired t test; ****p<0.0001, mean ± SD; n represents number of cells counted. (N-R) GRASP65 (N), GM130 (O), Giantin (P), Golgin-245 (Q), and TGN46 (R) W-Bs of the lysates of PC-3 cells treated with HCQ; β-actin is a loading control. All data presented are representative of at least three independent experiments.
Movie S3 from Targeting the ATF6-Mediated ER Stress Response and Autophagy Blocks Integrin-Driven Prostate Cancer Progression
Authors: Macke Amanda J. , Pachikov Artem N. , Divita Taylor E. , Morris Mary E. , LaGrange Chad A. , Holzapfel Melissa S. , Kubyshkin Anatoly V. , Zyablitskaya Evgeniya Y. , Makalish Tatiana P. , Eremenko Sergey N. , Qiu Haowen , Riethoven Jean-Jack M. , Hemstreet George P. , Petrosyan Armen
Published: July 2023

PC-3 cell treated with water, stained for Integrin αv (red), Gal-3 (green), EEA1 (magenta). Areas of 3-color colocalization are highlighted with white. Surfaces were reconstructed by Imaris.
Movie S1 from Targeting the ATF6-Mediated ER Stress Response and Autophagy Blocks Integrin-Driven Prostate Cancer Progression
Authors: Macke Amanda J. , Pachikov Artem N. , Divita Taylor E. , Morris Mary E. , LaGrange Chad A. , Holzapfel Melissa S. , Kubyshkin Anatoly V. , Zyablitskaya Evgeniya Y. , Makalish Tatiana P. , Eremenko Sergey N. , Qiu Haowen , Riethoven Jean-Jack M. , Hemstreet George P. , Petrosyan Armen
Published: July 2023

PC-3 cell treated with water, stained for Golgi (GRASP65, green) and MGAT3 (red). Surfaces were reconstructed by Imaris.
Supplementary Figure 8 from Targeting c-Jun Is a Potential Therapy for Luminal Breast Cancer Bone Metastasis
Authors: Han Yuxuan , Katayama Shota , Futakuchi Mitsuru , Nakamichi Kazuya , Wakabayashi Yutaro , Sakamoto Mai , Nakayama Jun , Semba Kentaro
Published: July 2023

Clinical clustering of breast cancer subtypes using c-Jun-regulated gene signatures.
Supplementary Figure 5 from Targeting c-Jun Is a Potential Therapy for Luminal Breast Cancer Bone Metastasis
Authors: Han Yuxuan , Katayama Shota , Futakuchi Mitsuru , Nakamichi Kazuya , Wakabayashi Yutaro , Sakamoto Mai , Nakayama Jun , Semba Kentaro
Published: July 2023

Clinical prognosis of c-Jun-regulated gene signatures.
Supplementary Figure 9 from Nrf2 Drives Hepatocellular Carcinoma Progression through Acetyl-CoA–mediated Metabolic and Epigenetic Regulatory Networks
Authors: Xi Caixia , Pang Junfeng , Barrett Amanda , Horuzsko Anatolij , Ande Satyanarayana , Mivechi Nahid F. , Zhu Xingguo
Published: July 2023

S9. MYC silencing reduced the expression of glycolysis genes in HepG2 cells.
Supplementary Figure 3 from Simultaneous Targeting of DNA Polymerase Theta and PARP1 or RAD52 Triggers Dual Synthetic Lethality in Homologous Recombination–Deficient Leukemia Cells
Authors: Sullivan-Reed Katherine , Toma Monika M. , Drzewiecka Malgorzata , Nieborowska-Skorska Margaret , Nejati Reza , Karami Adam , Wasik Mariusz A. , Sliwinski Tomasz , Skorski Tomasz
Published: July 2023

S3. Simultaneous inhibition of Polθ helicase and DNA polymerase activity exerted synergistic effect against RAD54-/- leukemia cells.
Supplementary Figure 2 from Simultaneous Targeting of DNA Polymerase Theta and PARP1 or RAD52 Triggers Dual Synthetic Lethality in Homologous Recombination–Deficient Leukemia Cells
Authors: Sullivan-Reed Katherine , Toma Monika M. , Drzewiecka Malgorzata , Nieborowska-Skorska Margaret , Nejati Reza , Karami Adam , Wasik Mariusz A. , Sliwinski Tomasz , Skorski Tomasz
Published: July 2023

S2. Phenotype of Polq-/-;Parp1-/- and Polq-/-;Rad52-/- mice.
Data from HCK promotes high-grade serous ovarian cancer tumorigenesis through CD44 and NOTCH3 signaling
Authors: Khella Christen A. , Franciosa Lucyann , Rodriguez-Rodriguez Lorna , Rajkarnikar Resha , Mythreye Karthikeyan , Gatza Michael L.
Published: July 2023

Abstract
High-grade serous ovarian cancer (HGSOC) is a highly aggressive and lethal subtype of ovarian cancer. While most patients initially respond to standard-of-care treatment, the majority will eventually relapse and succumb to their disease. Despite significant advances in our understanding of this disease, the mechanisms that govern the distinctions between HGSOC with good and poor prognosis remain unclear. In this study, we implemented a proteogenomic approach to analyze gene expression, proteomic and phosphoproteomic proﬁles of HGSOC tumor samples to identify molecular pathways that distinguish HGSOC tumors relative to clinical outcome. Our analyses identify significant upregulation of hematopoietic cell kinase (HCK) expression and signaling in poor prognostic HGSOC patient samples. Analyses of independent gene expression datasets and immunohistochemistry of patient samples confirmed increased HCK signaling in tumors relative to normal fallopian or ovarian samples and demonstrated aberrant expression in tumor epithelial cells. Consistent with the association between HCK expression and tumor aggressiveness in patient samples, in vitro phenotypic studies showed that HCK can, in part, promote cell proliferation, colony formation, and invasive capacity of cell lines. Mechanistically, HCK mediates these phenotypes, partly through CD44 and NOTCH3-dependent signaling, and inhibiting CD44 or NOTCH3 activity, either genetically or through gamma-secretase inhibitors, can revert HCK-driven phenotypes.
Implications: Collectively, these studies establish that HCK acts as an oncogenic driver of HGSOC through aberrant activation of CD44 and NOTCH3 signaling and identifies this network as a potential therapeutic opportunity in a subset of aggressive and recurrent HGSOC patients.
Data from Oncostatin-M and OSM-Receptor Feed-Forward Activation of MAPK Induces Separable Stem-like and Mesenchymal Programs
Authors: Polak Kelsey L. , Tamagno Ilaria , Parameswaran Neetha , Smigiel Jacob , Chan E. Ricky , Yuan Xueer , Rios Brenda , Jackson Mark W.
Published: July 2023

Abstract
Patients diagnosed with pancreatic ductal adenocarcinoma (PDAC) frequently present with advanced metastatic disease and exhibit a poor response to therapy, resulting in poor outcomes. The tumor microenvironment cytokine Oncostatin-M (OSM) initiates PDAC plasticity, inducing the reprogramming to a stem-like/mesenchymal state, which enhances metastasis and therapy resistance. Using a panel of PDAC cells driven through epithelial–mesenchymal transition (EMT) by OSM or the transcription factors ZEB1 or SNAI1, we find that OSM uniquely induces tumor initiation and gemcitabine resistance independently of its ability to induce a CD44HI/mesenchymal phenotype. In contrast, while ZEB1 and SNAI1 induce a CD44HI/mesenchymal phenotype and migration comparable with OSM, they are unable to promote tumor initiation or robust gemcitabine resistance. Transcriptomic analysis identified that OSM-mediated stemness requires MAPK activation and sustained, feed-forward transcription of OSMR. MEK and ERK inhibitors prevented OSM-driven transcription of select target genes and stem-like/mesenchymal reprogramming, resulting in reduced tumor growth and resensitization to gemcitabine. We propose that the unique properties of OSMR, which hyperactivates MAPK signaling when compared with other IL6 family receptors, make it an attractive therapeutic target, and that disrupting the OSM-OSMR-MAPK feed-forward loop may be a novel way to therapeutically target the stem-like behaviors common to aggressive PDAC.
Implications:
Small-molecule MAPK inhibitors may effectively target the OSM/OSMR-axis that leads to EMT and tumor initiating properties that promote aggressive PDAC.
Data from Nrf2 Drives Hepatocellular Carcinoma Progression through Acetyl-CoA–mediated Metabolic and Epigenetic Regulatory Networks
Authors: Xi Caixia , Pang Junfeng , Barrett Amanda , Horuzsko Anatolij , Ande Satyanarayana , Mivechi Nahid F. , Zhu Xingguo
Published: July 2023

Abstract
Correlations between the oxidative stress response and metabolic reprogramming have been observed during malignant tumor formation; however, the detailed mechanism remains elusive. The transcription factor Nrf2, a master regulator of the oxidative stress response, mediates metabolic reprogramming in multiple cancers. In a mouse model of hepatocellular carcinoma (HCC), through metabolic profiling, genome-wide gene expression, and chromatin structure analyses, we present new evidence showing that in addition to altering antioxidative stress response signaling, Nrf2 ablation impairs multiple metabolic pathways to reduce the generation of acetyl-CoA and suppress histone acetylation in tumors, but not in tumor-adjacent normal tissue. Nrf2 ablation and dysregulated histone acetylation impair transcription complex assembly on downstream target antioxidant and metabolic regulatory genes for expression regulation. Mechanistic studies indicate that the regulatory function of Nrf2 is low glucose dependent, the effect of which is demolished under energy refeeding. Together, our results implicate an unexpected effect of Nrf2 on acetyl-CoA generation, in addition to its classic antioxidative stress response regulatory activity, integrates metabolic and epigenetic programs to drive HCC progression.
Implications:
This study highlights that Nrf2 integrates metabolic and epigenetic regulatory networks to dictate tumor progression and that Nrf2 targeting is therapeutically exploitable in HCC treatment.
Data from Chromatin-associated SIN3B protects cancer cells from genotoxic stress-induced apoptosis and dictates DNA damage repair pathway choice
Authors: Morales-Valencia Jorge , Petit Coralie , Calderon Alexander , Saini Siddharth , David Gregory
Published: July 2023

Abstract
Transcription and DNA damage repair act in a coordinated manner. The scaffolding protein SIN3B serves as a transcriptional co-repressor of hundreds of cell-cycle-related genes. However, the contribution of SIN3B during the DNA damage response (DDR) remains unknown. Here, we show that SIN3B inactivation delays the resolution of DNA double-strand breaks (DSBs) and sensitizes cancer cells to DNA-damaging agents, including the chemotherapeutic drugs cisplatin and doxorubicin. Mechanistically, SIN3B is rapidly recruited to DNA damage sites where it directs the accumulation of MDC1. In addition, we show that SIN3B inactivation favors the engagement of the alternative NHEJ repair pathway over the canonical NHEJ. Altogether, our findings impute an unexpected function for the transcriptional co-repressor SIN3B as a gatekeeper of genomic integrity and a determining factor in the DNA repair choice pathway, and point to the inhibition of the SIN3B chromatin-modifying complex as a novel therapeutic vulnerability in cancer cells.

Implications: Identifying SIN3B as a modulator of DNA damage repair choice provides novel potential therapeutic avenues to sensitize cancer cells to cytotoxic therapies.
Table S8 from Systemic Treatments and Molecular Biomarkers for Perivascular Epithelioid Cell Tumors: A Single-institution Retrospective Analysis
Authors: Testa Stefano , Bui Nam Q. , Ganjoo Kristen N.
Published: July 2023

Table S8 shows median clinical PFS from first-line therapy in months, as well as 5-year clinical PFS rate from first-line therapy for the whole cohort.
Table S7 from Systemic Treatments and Molecular Biomarkers for Perivascular Epithelioid Cell Tumors: A Single-institution Retrospective Analysis
Authors: Testa Stefano , Bui Nam Q. , Ganjoo Kristen N.
Published: July 2023

Table S7 shows results of Cox proportional hazard analysis for overall survival in patients with malignant PEComa only.
Table S11 from Systemic Treatments and Molecular Biomarkers for Perivascular Epithelioid Cell Tumors: A Single-institution Retrospective Analysis
Authors: Testa Stefano , Bui Nam Q. , Ganjoo Kristen N.
Published: July 2023

Table S11 shows median clinical PFS for all treatment episodes in months, as well as 5-year clinical PFS rate for all treatment episodes in the whole cohort.
Table S1 from Systemic Treatments and Molecular Biomarkers for Perivascular Epithelioid Cell Tumors: A Single-institution Retrospective Analysis
Authors: Testa Stefano , Bui Nam Q. , Ganjoo Kristen N.
Published: July 2023

Table S1 shows a a description of study design, main findings and conclusions for the most relevant references in the study regarding management of patients with PEComas.
TABLE 4 from Systemic Treatments and Molecular Biomarkers for Perivascular Epithelioid Cell Tumors: A Single-institution Retrospective Analysis
Authors: Testa Stefano , Bui Nam Q. , Ganjoo Kristen N.
Published: July 2023

Cox PH analysis for PFS for all treatment episodes combined, regardless of line of therapy
Figure S7 from Systemic Treatments and Molecular Biomarkers for Perivascular Epithelioid Cell Tumors: A Single-institution Retrospective Analysis
Authors: Testa Stefano , Bui Nam Q. , Ganjoo Kristen N.
Published: July 2023

Figure S7 shows Kaplan-Meier curves for combined PFS in patients with PEComas, specifically showing effect of TP53 and TSC1/TSC2 mutational status, as well as uterine vs extra-uterine location on combined PFS.
Figure S2 from Systemic Treatments and Molecular Biomarkers for Perivascular Epithelioid Cell Tumors: A Single-institution Retrospective Analysis
Authors: Testa Stefano , Bui Nam Q. , Ganjoo Kristen N.
Published: July 2023

Figure S2 shows an Oncoplot of the mutations discovered in patients for which next-generation sequencing testing was available.
Figure S1 from Systemic Treatments and Molecular Biomarkers for Perivascular Epithelioid Cell Tumors: A Single-institution Retrospective Analysis
Authors: Testa Stefano , Bui Nam Q. , Ganjoo Kristen N.
Published: July 2023

Supplementary Figure S1 showing study flow diagram with details regarding the pathology cases review and patient selection process.
Figure S7 from Remodeling of Stromal Immune Microenvironment by Urolithin A Improves Survival with Immune Checkpoint Blockade in Pancreatic Cancer
Authors: Mehra Siddharth , Garrido Vanessa T. , Dosch Austin R. , Lamichhane Purushottam , Srinivasan Supriya , Singh Samara P. , Zhou Zhiqun , De Castro Silva Iago , Joshi Chandrashekar , Ban Yuguang , Datta Jashodeep , Gilboa Eli , Merchant Nipun B. , Nagathihalli Nagaraj S.
Published: July 2023

Recorded body weights of PKT mice treated with Uro A, aPD-1 and Uro A+aPD-1.
Figure S3 from Remodeling of Stromal Immune Microenvironment by Urolithin A Improves Survival with Immune Checkpoint Blockade in Pancreatic Cancer
Authors: Mehra Siddharth , Garrido Vanessa T. , Dosch Austin R. , Lamichhane Purushottam , Srinivasan Supriya , Singh Samara P. , Zhou Zhiqun , De Castro Silva Iago , Joshi Chandrashekar , Ban Yuguang , Datta Jashodeep , Gilboa Eli , Merchant Nipun B. , Nagathihalli Nagaraj S.
Published: July 2023

Gating strategies used for flow cytometry analysis.