bluuebunny/crossref_metadata_2025 huggingface dataset:
A laboratory framework for ongoing optimization of amplification-based genomic surveillance programs
Authors: Lam Connie , Johnson-Mackinnon Jessica , Basile Kerri , Fong Winkie , Suster Carl J.E. , Gall Mailie , Agius Jessica , Chandra Shona , Draper Jenny , Martinez Elena , Drew Alexander , Wang Qinning , Chen Sharon C. , Kok Jen , Dwyer Dominic E. , Sintchenko Vitali , Rockett Rebecca J.
Published: November 2023

Constantly evolving viral populations affect the specificity of primers and the quality of genomic surveillance. This study presents a framework for the continuous optimization of sequencing efficiency for public health surveillance based on the ongoing evolution of the COVID-19 pandemic. SARS-CoV-2 genomic clustering capacity based on three amplification-based whole genome sequencing schemes was assessed using decreasing thresholds of genome coverage and measured against epidemiologically linked cases. The overall genome coverage depth and individual amplicon depth were used to calculate an amplification efficiency metric. Significant loss of genome coverage over time was documented, which was recovered by optimization of primer pooling or implementation of new primer sets. A minimum of 95% genome coverage was required to cluster 94% of epidemiologically defined SARS-CoV-2 transmission events. Clustering resolution fell to 70% when only 85% genome coverage was achieved. The framework presented in this study can provide public health genomic surveillance programs with a systematic process to ensure an agile and effective laboratory response during rapidly evolving viral outbreaks.

IMPORTANCE

This study provides a laboratory framework to ensure ongoing relevance and performance of amplification-based whole genome sequencing to strengthen public health surveillance during extended outbreaks or pandemics. The framework integrates regular reviews of the performance of a genomic surveillance system and highlights the importance of ongoing monitoring and the identification and implementation of improvements to whole genome sequencing methods to enhance public health responses to pathogen outbreaks.
Efficient cross-protection against serotype 4/8a fowl adenoviruses (FAdVs): recombinant FAdV-4 with FAdV-8a Fiber
Authors: Lu Yixuan , Yuan Yaqin , Jiang Huiru , Xu Zhenqi , Guo Yiwen , Cao Xudong , Li Tuofan , Wan Zhimin , Shao Hongxia , Qin Aijian , Xie Quan , Ye Jianqiang
Published: November 2023

Recently, the infection of fowl adenoviruses (FAdVs) in chicken flocks has caused huge economic losses to the poultry industry in China. Although immunization with Fiber protein can provide autogenous protection of FAdVs, no commercial multivalent vaccines are available for the prevention and control of FAdVs. In this study, a novel recombinant virus FAdV4-F/8a-rF2 expressing the Fiber of FAdV-8a was generated through CRISPR-Cas9 and Cre-LoxP system by using the template virus FA4-EGFP. FAdV4-F/8a-rF2 not only exhibited a similar replication capacity to the wild-type FAdV-4 in Leghorn male hepatoma (LMH) cells but was also highly attenuated to specific pathogen free (SPF) chickens. Moreover, the inoculation of FAdV4-F/8a-rF2 could induce high neutralizing antibodies and provide full protection against both FAdV-4 and FAdV-8a. All these data demonstrate that the recombinant virus FAdV4-F/8a-rF2 developed here can be used as an attenuated bivalent vaccine candidate for the prevention and control of both FAdV-4 and FAdV-8a.

IMPORTANCE

Epidemiological data reveal that FAdV-4 and FAdV-8a are the dominant serotypes of FAdVs in the poultry industry in China. Although three commercial inactivated vaccines against FAdV-4 have been licensed in China, the bivalent vaccine against both FAdV-4 and FAdV-8a is not available. Here, we used CRISPR-Cas9 and Cre-LoxP system to generate a recombinant virus FAdV4-F/8a-rF2 expressing the Fiber of FAdV-8a. Notably, FAdV4-F/8a-rF2 was highly attenuated and could provide efficient protection against both FAdV-4 and FAdV-8a in the chicken infection model, highlighting the applaudable application of FAdV4-F/8a-rF2 as a novel live-attenuated bivalent vaccine against the diseases caused by the infection of FAdV-4 and FAdV-8a.
Determinants of practice for providing decision coaching to facilitate informed values-based decision-making: protocol for a mixed-methods systematic review
Authors: Berger-Höger Birte , Lewis Krystina B , Cherry Katherine , Finderup Jeanette , Gunderson Janet , Kaden Jana , Kienlin Simone , Rahn Anne C , Sikora Lindsey , Stacey Dawn , Steckelberg Anke , Zhao Junqiang
Published: November 2023

Introduction

Decision coaching is a non-directive approach to support patients to prepare for making health decisions. It is used to facilitate patients’ involvement in informed values-based decision-making and use of evidence-based health information. A recent systematic review revealed low certainty evidence for its effectiveness with and without evidence-based information. However, there may be opportunities to improve the study and use of decision coaching in clinical practice by systematically investigating its determinants of practice. We aim to conduct a systematic review to identify and synthesise the determinants of practice for providing decision coaching to facilitate patient involvement in decision-making from multiple perspectives that influence its use.

Methods and analysis

We will conduct a mixed-methods systematic review guided by the Cochrane’ Handbook of Systematic Reviews. We will include studies reporting determinants of practice influencing decision coaching with or without evidence-based patient information with adults making a health decision for themselves or a family member. Systematic literature searches will be conducted in Medline, EMBASE, Cochrane CENTRAL and PsycINFO via Ovid and CINAHL via EBSCO including quantitative, qualitative and mixed-methods study designs. Additionally, experts in the field will be contacted.

Two reviewers will independently screen and extract data. We will synthesise determinants using deductive and inductive qualitative content analysis and a coding frame developed specifically for this review based on a taxonomy of barriers and enablers of shared decision-making mapped onto the major domains of the Consolidated Framework for Implementation Research. We will assess the quality of included studies using the Mixed Methods Appraisal Tool.

Ethics and dissemination

Ethical approval is not required as this systematic review involves only previously published literature. The results will be published in a peer-reviewed journal, presented at scientific conferences and disseminated to relevant consumer groups.

PROSPERO registration number

CRD42022338299.
Assessing the burden of HPV-related head and neck cancers in mainland China: protocol of a nationwide, multisite, cross-sectional study
Authors: Wang Wei , Song Cheng , Su Zheng , Kothari Smita , Chen Ya-Ting , Liu Yin , Wu Shu-Yu , Panchal Ravi , Morais Edith , Zhang Shao-Kai , Yin Jian , Qiao You-Lin , Roberts Craig
Published: November 2023

Background

Persistent human papillomavirus (HPV) infection is a known cause of a subset of head and neck cancers (HNCs). In the last two decades, the proportion of HNCs attributable to HPV infection has increased worldwide, notably the oropharyngeal cancers. However, the trend of HPV-related HNC burden is not clearly understood yet in China. Thus, the absoluteburdenof HPV-related head andneck cancers in China (BROADEN-China) will be conducted to estimate the proportion of HNCs attributable to HPV infection, per anatomic site, by genotype, in three time periods (2008–2009, 2013–2014 and 2018–2019).

Methods and analysis

BROADEN-China is a nationwide, multisite, cross-sectional study. A stratified, multistage, non-randomised cluster sampling method will be used to select 2601 patients with HNC from 14 hospitals across seven regions, based on population density in China. Patients with formalin-fixed paraffin-embedded tissue samples collected prior to treatment induction during three time periods will be included, and factors (eg, smoking status, alcohol consumption, betel nut chewing, Epstein-Barr virus, teeth loss, etc) associated with HNC will be assessed. HPV testing (HPV-DNA, HPV-mRNA and p16INK4aimmunohistochemistry) and histological diagnosis of the tissue samples will be conducted at a central laboratory.

The study protocol and all required documents have been submitted for review and approval to the Independent Ethics Committees of all the participating sites. The informed consent was waived for all participants and all the recorded data will be treated as confidential.

We have included 14 hospitals as our participating sites, of which Henan Cancer Hospital is the leading site. The study has been approved by the independent ethics committees of the leading site on 3 December 2020. The other 13 participating site names of ethics committee and IRB that have approved this study.
Continuity of care and consultation mode in general practice: a cross-sectional and longitudinal study using patient-level and practice-level data from before and during the COVID-19 pandemic in England
Authors: Parry Will , Fraser Caroline , Crellin Elizabeth , Hughes Jay , Vestesson Emma , Clarke Geraldine M.
Published: November 2023

Objectives

Investigate trends in continuity of care with a general practitioner (GP) before and during the COVID-19 pandemic. Identify whether continuity of care is associated with consultation mode, controlling for other patient and practice characteristics.

Design

Retrospective cross-sectional and longitudinal observational studies.

Setting

Primary care records from 389 general practices participating in Clinical Practice Research Datalink Aurum in England.

Participants

In the descriptive analysis, 100 000+ patients were included each month between April 2018 and April 2021. Modelling of the association between continuity of care and consultation mode focused on 153 475 and 125 298 patients in index months of February 2020 (before the pandemic) and February 2021 (during the pandemic) respectively, and 76 281 patients inbothindex months.

Primary and secondary outcomes measures

The primary outcome measure was the Usual Provider of Care index. Secondary outcomes included the Bice-Boxerman index and count of consultations with the most frequently seen GP.

Results

Continuity of care was gradually declining before the pandemic but stabilised during it. There were consistent demographic, socioeconomic and regional differences in continuity of care. An average of 23% of consultations were delivered remotely in the year to February 2020 compared with 76% in February 2021. We found little evidence consultation mode was associated with continuity at the patient level, controlling for a range of covariates. In contrast, patient characteristics and practice-level supply and demand were associated with continuity.

Conclusions

We set out to examine the association of consultation mode with continuity of care but found that GP supply and patient demand were much more important. To improve continuity for patients, primary care capacity needs to increase. This requires sufficient, long-term investment in clinicians, staff, facilities and digital infrastructure. General practice also needs to transform ways of working to ensure continuity for those that need it, even in a capacity-constrained environment.
The cyclic performance of column base plate connections using different types of stiffeners
Authors: Al-Sharmootee Mohammed , Lavassani Seyed Hossein Hosseini , Hosseini Mir Hamid , Ali Mahmoud
Published: November 2023

Column base connections represent the support system of a structure, and they should be strong enough to sustain the transmitted demands between the columns and foundation. This study describes numerically the performance of strengthened column base plate connections under cyclic loading. Four types of stiffeners were considered in the analysis: bracket plates, angles, channels with vertical stiffeners, and built-up stiffeners. The efficiency of used stiffeners, the cyclic performance of the strengthened connections, and along with the failure modes were investigated. The numerical results showed that all the proposed strengthening methods have sufficient flexural strength and stiffness higher than the column. A pinched hysteretic response was observed for all strengthened connections under the applied cyclic loading. The built-up stiffener presented the maximum moment capacity and rotational stiffness among the other configurations. Using strengthened connections with more stiffeners made the anchor rods the fuse elements in the connection.
The individual color pattern on the back of Bufotes viridis balearicus (Boettger, 1880) allows individual photo-identification recognition for population studies
Authors: Lassnig Nil , Guasch-Martínez Sergi , Pinya Samuel
Published: November 2023

This study explores the potential of photo-identification methods (PIMs) as a viable, non-invasive, and ethical tool for wildlife studies, with a specific focus on anuran species such as Bufotes viridis balearicus (Boettger, 1880). Although the automatic photo-identification suite (APHIS) software was initially designed for lizard identification, our research shows its adaptability for anuran species, achieving a high detection accuracy rate of 95.28%, thus obtaining outstanding and higher values in compared to previous studies on this species. Crucially, our findings indicate that the success of PIM and the efficacy of image identification software like APHIS is dependent on the quality and standardization of the images collected. The study also underscores the importance of practical experience and continuous learning for the optimal utilization of software like APHIS. Despite occasional false rejected matches, the overall strong performance metrics with low false rejection rate demonstrate that these instances do not significantly impact the reliability of the technique. Thus, this research highlights the importance of careful implementation, continuous learning, and image quality control in leveraging the full potential of image identification software in wildlife studies.
Unsupervised Neural Manifold Alignment for Stable Decoding of Movement from Cortical Signals
Authors: Ganjali Mohammadali , Mehridehnavi Alireza , Rakhshani Sajed , Khorasani Abed
Published: November 2023

The stable decoding of movement parameters using neural activity is crucial for the success of brain-machine interfaces (BMIs). However, neural activity can be unstable over time, leading to changes in the parameters used for decoding movement, which can hinder accurate movement decoding. To tackle this issue, one approach is to transfer neural activity to a stable, low-dimensional manifold using dimensionality reduction techniques and align manifolds across sessions by maximizing correlations of the manifolds. However, the practical use of manifold stabilization techniques requires knowledge of the true subject intentions such as target direction or behavioral state. To overcome this limitation, an automatic unsupervised algorithm is proposed that determines movement target intention before manifold alignment in the presence of manifold rotation and scaling across sessions. This unsupervised algorithm is combined with a dimensionality reduction and alignment method to overcome decoder instabilities. The effectiveness of the BMI stabilizer method is represented by decoding the two-dimensional (2D) hand velocity of two rhesus macaque monkeys during a center-out-reaching movement task. The performance of the proposed method is evaluated using correlation coefficient and R-squared measures, demonstrating higher decoding performance compared to a state-of-the-art unsupervised BMI stabilizer. The results offer benefits for the automatic determination of movement intents in long-term BMI decoding. Overall, the proposed method offers a promising automatic solution for achieving stable and accurate movement decoding in BMI applications.
Analysis of thermal conductivity performance for magnetized Sutterby fluid capturing magnetic dipole and viscous dissipation aspects
Authors: Khan Waqar Azeem , Tabrez Muhammad , Hussain Iftikhar , Ali Mehboob , Waqas Muhammad
Published: November 2023

The study is accomplished to explore the pioneering of a two-dimensional ferromagnetic fluid flow over a flat elastic sheet with the magnetic dipole effect. The recent flow design was selected as it is mostly applicable in bioengineering as well as engineering fields that includes magnetic drug targeting systems. In this paper, the impacts of thermal radiation and magnetic dipole in flow of ferromagnetic Sutterby fluid for a stretching surface are examined. Some suitable similarity transformations are exploited to achieve the system of nonlinear ODEs from set of PDEs, then acquired ODEs are resolved by numerical scheme known as bvp4c technique. Impacts of ferromagnetic interaction parameter, viscous dissipation and curie temperature are perceived for velocity as well as temperature fields. Furthermore, velocity as well as thermal gradients are deliberated and scrutinized pictorially.
Numerical analysis for 3D time-dependent Sutterby nanofluid flow capturing features of variable thermal conductivity and heat sink-source aspects
Authors: Hussain Zubair , Khan Waqar Azeem , Ali Mehboob , Waqas Muhammad
Published: November 2023

Presently, due to its extraordinary mechanical, thermal, electrical and biomedical facets nanofluids deliver several prospects to exaggerate the propensity of isothermal systems by augmenting the conductivity features of the host fluids. In various areas of the energy partition, nanoparticles show a remarkable measure in energy storage, energy variation, and energy convertible, i.e. thermoelectric plans, petroleum cells, supercapacitors, stellar cells, rechargeable batteries, light-radiating diode and carbon-based light-radiating diode, smart coatings. In this current conversation, we anticipated an unsteady 3D flow of the Sutterby nanofluid consequence of a bidirectional extended surface. To envision the thermophoresis and Brownian motion properties in Sutterby’s nanofluid, the Buongiorno association is utilized in an additional refined technique. Variable thermal conductivity with heat source/sink property occurred deliberated considering heat transmission techniques. The appropriate transformation is applied for transposing the PDEs into nonlinear ODEs. For numerical results, the bvp4c programmed is prerequisite for elucidating the subsequent Ordinary differential equations. The distinct performance of the Sutterby nanofluid temperature and the concentration field are designated and discussed in the physical parameter’s aspect. It is clear that the temperature of the Sutterby fluid decreases with respect to the ratio of stretching rates parameter and similar developments are observed for the thermophoresis and Brownian motion parameters. Furthermore, the concentration profile declines for sophisticated estimates of the Lewis number and thermophoresis parameters.
Financial fraud detection: A comparative study of quantum machine learning models
Authors: Innan Nouhaila , Khan Muhammad Al-Zafar , Bennai Mohamed
Published: November 2023

In this research, a comparative study of four Quantum Machine Learning (QML) models was conducted for fraud detection in finance. We proved that the Quantum Support Vector Classifier model achieved the highest performance, with F1 scores of [Formula: see text] for fraud and nonfraud classes. Other models like the Variational Quantum Classifier (VQC), Estimator Quantum Neural Network (QNN), and Sampler QNN demonstrate promising results, propelling the potential of QML classification for financial applications. While they exhibit certain limitations, the insights attained pave the way for future enhancements and optimization strategies. However, challenges exist, including the need for more efficient quantum algorithms and larger and more complex datasets. This paper provides solutions to overcome current limitations and contributes new insights to the field of QML in fraud detection, with important implications for its future development.
Variation in the Incidence and Type of Full versus Mosaic Segmental Aneuploidies Identified in Blastocysts Undergoing PGT-A
Authors: Cuman Carly , Green Mark P. , Willats Elissa , Hardy Tristan , Zander-Fox Deirdre
Published: November 2023

Objectives: The primary aim of this study was to investigate the incidence of segmental aneuploidies (full vs. mosaic) in embryos biopsied for Preimplantation Genetic Testing with Aneuploidy (PGT-A) screening using low-coverage whole genome sequencing (WGS). The secondary aim was to investigate factors that may be associated with segmental aneuploidy rates, including blastocyst developmental stage and quality.

Methods: This study involved a retrospective analysis of cycle and PGT-A data from 8,153 blastocysts biopsied from 2,522 patients at four Monash IVF Victorian clinics between January 2015 and June 2021. All biopsies were processed using the Veriseq PGS Kit (Illumina) and analyzed using Bluefuse Multi software (Illumina) with a conclusive PGT-A result. Segmental aneuploidy was reported with a minimum resolution of greater than or equal to 10[Formula: see text]Mb. The reporting range for mosaicism was 20%–70% loss/gain in copy number. Statistical significance was established at a P-value of less than 0.05.

Results: Segmental aneuploidies (full and/or mosaic) were reported in 682/8,153 (8.4%) biopsied embryos. Analysis of the types of segmental aneuploidy showed a higher proportion of deletions (423/8,153; 5.2%) compared to duplications (210/8,153; 2.6% [[Formula: see text]] plus a small portion with both duplications and deletions detected 49/8153; 0.6% [[Formula: see text]]). The incidence of segmental aneuploidies appeared to increase in correlation with chromosome size. Segregation of embryos by blastocyst stage indicated an increase in the incidence of segmental aneuploidies in early blastocysts (9/64; 14.1%) compared with expanding/expanded (39/475, 8.2%, [[Formula: see text]] and hatching/hatched blastocysts [634/7614, 8.3%; [Formula: see text]]). Furthermore, the incidence of segmental aneuploidies significantly increased as blastocyst overall grade decreased (Grade A 71/1,429, 5.0%; Grade B 298/3,764, 7.9%; Grade C 313/2,960, 10.6%; [Formula: see text]). Of the segmental aneuploidies detected, 425/682 (62.3%) were present at a mosaic level.

Conclusions: Segmental aneuploidy rates varied between blastocyst stage and grades, with a significant proportion of segmental aneuploidies being detected at the mosaic level. Our data highlights that segmental aneuploidies, both at the full and mosaic level, are associated with lower blastocyst quality and poorer embryo development.
Progestin-Primed Ovarian Stimulation versus GnRH Antagonist Protocol for Ovarian Stimulation in IVF: A Prospective Pilot Study
Authors: Le Tien K. , Le Xuyen H. , Nguyen Duy L. , Vu Anh L. , Vuong Lan N.
Published: November 2023

Background: Progestin-primed ovarian stimulation (PPOS) has been proposed as an alternative to conventional gonadotropin-releasing hormone (GnRH) antagonist protocol for ovarian stimulation in in vitro fertilization (IVF). The aim of PPOS is to provide an effective, patient-friendly treatment. However, studies comparing outcomes after the use of PPOS and GnRH antagonist protocol in IVF have shown mixed results. This study compared ongoing pregnancy rates after the use of PPOS versus GnRH antagonist protocol for ovarian stimulation in IVF.

Methods: This prospective pilot study was conducted at a single IVF center. Women aged 18–35 years old with an anti-Müllerian hormone (AMH) level greater than or equal to 1.2[Formula: see text]ng/mL or an antral follicle count (AFC) greater than or equal to 5 who were undergoing their first IVF cycle were allocated to undergoing ovarian stimulation using PPOS (dydrogesterone 20[Formula: see text]mg/day started on the day of gonadotropin) or a GnRH antagonist protocol (fixed regimen from stimulation day 5). The primary outcome was the ongoing pregnancy rate (at 12 weeks’ gestation).

Results: The study included 30 women (15 in each treatment group). Baseline characteristics were similar between groups. The ongoing pregnancy rate was 7/15 (46.7%) in the PPOS group and 8/15 (53.3%) in the GnRH antagonist group ([Formula: see text]); the number of oocytes retrieved and fertilization rates were also comparable between groups. One case of mild ovarian hyperstimulation syndrome (OHSS) occurred in the GnRH antagonist group.

Conclusions: This pilot study showed similar ongoing pregnancy rates after the use of a PPOS protocol and a conventional GnRH antagonist protocol for ovarian stimulation in IVF. Additional studies with larger sample sizes are needed to confirm these findings.
Analysis and Design of Identity Authentication for IoT Devices in the Blockchain Using Hashing and Digital Signature Algorithms
Authors: Wang Lei , Yuan Ying , Ding Yan
Published: November 2023

This paper proposes a blockchain-based identity authentication (BA) scheme for IoT devices to solve the authentication security problem of IoT devices. The BA scheme uses hashing and digital signature algorithms to achieve integrity and nonrepudiation of authentication messages. Blockchain technology is used to achieve decentralised and distributed storage and management of authentication data. Besides, the BA scheme uses the idea of trust domains and trust credentials to establish a master-slave connection between IoT devices. The BA scheme is then compared with the existing four schemes and analysed from six perspectives to show that the BA scheme has better security. Also, the results show that the BA scheme has reasonable computational and storage overhead. Finally, the advantages of the BA scheme over traditional centralised and existing blockchain-based authentication schemes are compared and analysed. The results show that it can perfectly solve the problem of overreliance on trusted third parties in traditional authentication schemes.
Analytical Validation of MINI‐PET as Point‐of‐Care for Erythrocyte Sedimentation Rate Measure in Horses
Authors: Pieroni Carolina , Grassi Andrea , Pantoli Marianna , Berretti Mirko , Messina Stefano , Giovannini Chiara , Lubas George , Diamanti Daniela
Published: November 2023

The erythrocyte sedimentation rate (ESR) is a widely used diagnostic assay in human medicine but nowadays poorly applied in veterinary medicine. This test measures the speed (millimeters per hour) at which red blood cells settle in a whole anticoagulated blood tube. In human medicine, high ESR values are associated with various disorders, including infections, rheumatoid arthritis, oncologic diseases, and other inflammatory conditions. The ESR can also be influenced by some factors such as age and gender. In veterinary medicine, the ESR with the Westergren manual method was almost forgotten over the years due to blood consumption and long turn‐around time. The instrument MINI‐PET, using a modified Westergren method, does not require blood consumption or release waste product and recently has been applied in canine medicine. The aims of the study in the horse were as follows: to establish the appropriate time to read the ESR with the Westergren reference method; to compare the MINI‐PET ESR results with the reference technique; to assess the ESR reference intervals with MINI‐PET; and to establish the ESR stability from collection at different time points by MINI‐PET. Using 150 horses, we established 60 minutes as the appropriate time for ESR reading with the Westergren method. Moreover, ESR results obtained in 8 minutes with MINI‐PET showed a good correlation with the Westergren ESR. Reference intervals (RIs) with MINI‐PET were established in mm/h for the healthy horses (geldings 18.6–100.1; stallions, 13.8–55.7; and mares 1–73.7) according to the American Society of Veterinary Clinical Pathology guidelines. In addition, the ESR stability from the blood collection time was evaluated in the MINI‐PET on 15 horses: at room temperature, ESR is stable up to 8 hours and at 4°C up to 24 hours. In conclusion, MINI‐PET represents a rapid and reliable tool for measuring ESR in horses, offering a valid option to replace the traditional manual technique.
Supplementary Data from Faecalibacterium prausnitzii Abrogates Intestinal Toxicity and Promotes Tumor Immunity to Increase the Efficacy of Dual CTLA4 and PD-1 Checkpoint Blockade
Authors: Gao Yaqi , Xu Pingping , Sun Danfeng , Jiang Yi , Lin Xiao-Lin , Han Ting , Yu Jun , Sheng Chunquan , Chen Haoyan , Hong Jie , Chen Yingxuan , Xiao Xiu-Ying , Fang Jing-Yuan
Published: November 2023

Supplementary Data
Supplementary Data from Faecalibacterium prausnitzii Abrogates Intestinal Toxicity and Promotes Tumor Immunity to Increase the Efficacy of Dual CTLA4 and PD-1 Checkpoint Blockade
Authors: Gao Yaqi , Xu Pingping , Sun Danfeng , Jiang Yi , Lin Xiao-Lin , Han Ting , Yu Jun , Sheng Chunquan , Chen Haoyan , Hong Jie , Chen Yingxuan , Xiao Xiu-Ying , Fang Jing-Yuan
Published: November 2023

Supplementary table
Supplementary Data from Cross-talk between PARN and EGFR–STAT3 Signaling Facilitates Self-Renewal and Proliferation of Glioblastoma Stem Cells
Authors: Yin Jinlong , Seo Yoona , Rhim Jiho , Jin Xiong , Kim Tae Hoon , Kim Sung Soo , Hong Jun-Hee , Gwak Ho-Shin , Yoo Heon , Park Jong Bae , Kim Jong Heon
Published: November 2023

Supplementary Data
Supplemental Figure S4 from SETD2 Deficiency Confers Sensitivity to Dual Inhibition of DNA Methylation and PARP in Kidney Cancer
Authors: Zhou Xinyi , Sekino Yohei , Li Hong-Tao , Fu Guanghou , Yang Zhi , Zhao Shuqing , Gujar Hemant , Zu Xiongbing , Weisenberger Daniel J. , Gill Inderbir S. , Tulpule Varsha , D’souza Anishka , Quinn David I. , Han Bo , Liang Gangning
Published: November 2023

Supplemental Figure S4
Supplemental Figure S3 from SETD2 Deficiency Confers Sensitivity to Dual Inhibition of DNA Methylation and PARP in Kidney Cancer
Authors: Zhou Xinyi , Sekino Yohei , Li Hong-Tao , Fu Guanghou , Yang Zhi , Zhao Shuqing , Gujar Hemant , Zu Xiongbing , Weisenberger Daniel J. , Gill Inderbir S. , Tulpule Varsha , D’souza Anishka , Quinn David I. , Han Bo , Liang Gangning
Published: November 2023

Supplemental Figure S3
Supplemental Figure S1 from SETD2 Deficiency Confers Sensitivity to Dual Inhibition of DNA Methylation and PARP in Kidney Cancer
Authors: Zhou Xinyi , Sekino Yohei , Li Hong-Tao , Fu Guanghou , Yang Zhi , Zhao Shuqing , Gujar Hemant , Zu Xiongbing , Weisenberger Daniel J. , Gill Inderbir S. , Tulpule Varsha , D’souza Anishka , Quinn David I. , Han Bo , Liang Gangning
Published: November 2023

Supplemental Figure S1
Table S4 from A Cell Surface-Binding Antibody Atlas Nominates a MUC18-Directed Antibody–Drug Conjugate for Targeting Melanoma
Authors: Shi Jing , Jiao Tao , Guo Qian , Weng Weining , Ma Linjie , Zhang Qing , Wang Lijun , Zhang Jianjian , Chen Caiwei , Huang Yaling , Wang Mingqiao , Pan Rong , Tang Yanfang , Hu Wenhao , Meng Tao , Liu Shu-Hui , Guo Jun , Kong Yan , Meng Xun
Published: November 2023

TK parameters of Non-GLP toxicity studies in monkeys
Supplementary video 4 from Stroma-Mediated Breast Cancer Cell Proliferation Indirectly Drives Chemoresistance by Accelerating Tumor Recovery between Chemotherapy Cycles
Authors: Miroshnychenko Daria , Miti Tatiana , Kumar Pragya , Miller Anna , Laurie Mark , Giraldo Nathalia , Bui Marilyn M. , Altrock Philipp M. , Basanta David , Marusyk Andriy
Published: November 2023

Time lapse video of MDA468 cells response to a 6 hour exposure to 0.125 μM
doxorubicin, in CAF CM. Microscopy photos were taken every 12 hours
Table S3 from A Cell Surface-Binding Antibody Atlas Nominates a MUC18-Directed Antibody–Drug Conjugate for Targeting Melanoma
Authors: Shi Jing , Jiao Tao , Guo Qian , Weng Weining , Ma Linjie , Zhang Qing , Wang Lijun , Zhang Jianjian , Chen Caiwei , Huang Yaling , Wang Mingqiao , Pan Rong , Tang Yanfang , Hu Wenhao , Meng Tao , Liu Shu-Hui , Guo Jun , Kong Yan , Meng Xun
Published: November 2023

Summary of repeated dose toxicity studies in monkeys
Supplementary Data from Stroma-Mediated Breast Cancer Cell Proliferation Indirectly Drives Chemoresistance by Accelerating Tumor Recovery between Chemotherapy Cycles
Authors: Miroshnychenko Daria , Miti Tatiana , Kumar Pragya , Miller Anna , Laurie Mark , Giraldo Nathalia , Bui Marilyn M. , Altrock Philipp M. , Basanta David , Marusyk Andriy
Published: November 2023

mathematical methods supplementary
Merged supplementary figures from Stroma-Mediated Breast Cancer Cell Proliferation Indirectly Drives Chemoresistance by Accelerating Tumor Recovery between Chemotherapy Cycles
Authors: Miroshnychenko Daria , Miti Tatiana , Kumar Pragya , Miller Anna , Laurie Mark , Giraldo Nathalia , Bui Marilyn M. , Altrock Philipp M. , Basanta David , Marusyk Andriy
Published: November 2023

Merged supplementary figures 1-8
Supplementary Data from Galectin-3 Cooperates with CD47 to Suppress Phagocytosis and T-cell Immunity in Gastric Cancer Peritoneal Metastases
Authors: Fan Yibo , Song Shumei , Li Yuan , Dhar Shilpa S. , Jin Jiankang , Yoshimura Katsuhiro , Yao Xiaodan , Wang Ruiping , Scott Ailing W. , Pizzi Melissa Pool , Wu Jingjing , Ma Lang , Calin George A. , Hanash Samir , Wang Linghua , Curran Michael , Ajani Jaffer A.
Published: November 2023

Supplementary table
Supplementary Tables from Targeting the Metabolic Enzyme PGAM2 Overcomes Enzalutamide Resistance in Castration-Resistant Prostate Cancer by Inhibiting BCL2 Signaling
Authors: Li Zhen , Ning Kang , Zhao Diwei , Zhou Zhaohui , Zhao Junliang , Long Xingbo , Yang Zhenyu , Chen Dong , Cai XinYang , Hong Lexuan , Zhang Luyao , Zhou Fangjian , Wang Jun , Li Yonghong
Published: November 2023

Supplementary Tables
Supplementary Data from Galectin-3 Cooperates with CD47 to Suppress Phagocytosis and T-cell Immunity in Gastric Cancer Peritoneal Metastases
Authors: Fan Yibo , Song Shumei , Li Yuan , Dhar Shilpa S. , Jin Jiankang , Yoshimura Katsuhiro , Yao Xiaodan , Wang Ruiping , Scott Ailing W. , Pizzi Melissa Pool , Wu Jingjing , Ma Lang , Calin George A. , Hanash Samir , Wang Linghua , Curran Michael , Ajani Jaffer A.
Published: November 2023

Supplementary method
Supplementary Data from The Genetic, Pharmacogenomic, and Immune Landscapes Associated with Protein Expression across Human Cancers
Authors: Chen Chengxuan , Liu Yuan , Li Qiang , Zhang Zhao , Luo Mei , Liu Yaoming , Han Leng
Published: November 2023

Table S1
Data from Oncogenic KRASG12D Reprograms Lipid Metabolism by Upregulating SLC25A1 to Drive Pancreatic Tumorigenesis
Authors: Zhang Ruowen , Peng Xiaogang , Du James Xianxing , Boohaker Rebecca , Estevao Igor L. , Grajeda Brian I. , Cox Marc B. , Almeida Igor C. , Lu Weiqin
Published: November 2023

Abstract
Pancreatic cancer is a highly lethal disease with obesity as one of the risk factors. Oncogenic KRAS mutations are prevalent in pancreatic cancer and can rewire lipid metabolism by altering fatty acid (FA) uptake, FA oxidation (FAO), and lipogenesis. Identification of the underlying mechanisms could lead to improved therapeutic strategies for treating KRAS-mutant pancreatic cancer. Here, we observed that KRASG12D upregulated the expression of SLC25A1, a citrate transporter that is a key metabolic switch to mediate FAO, fatty acid synthesis, glycolysis, and gluconeogenesis. In genetically engineered mouse models and human pancreatic cancer cells, KRASG12D induced SLC25A1 upregulation via GLI1, which directly stimulated SLC25A1 transcription by binding its promoter. The enhanced expression of SLC25A1 increased levels of cytosolic citrate, FAs, and key enzymes in lipid metabolism. In addition, a high-fat diet (HFD) further stimulated the KRASG12D-GLI1-SLC25A1 axis and the associated increase in citrate and FAs. Pharmacologic inhibition of SLC25A1 and upstream GLI1 significantly suppressed pancreatic tumorigenesis in KrasG12D/+ mice on a HFD. These results reveal a KRASG12D-GLI1-SLC25A1 regulatory axis, with SLC25A1 as an important node that regulates lipid metabolism during pancreatic tumorigenesis, thus indicating an intervention strategy for oncogenic KRAS-driven pancreatic cancer.
Significance:
Upregulation of SLC25A1 induced by KRASG12D-GLI1 signaling rewires lipid metabolism and is exacerbated by HFD to drive the development of pancreatic cancer, representing a targetable metabolic axis to suppress pancreatic tumorigenesis.
Data from Faecalibacterium prausnitzii Abrogates Intestinal Toxicity and Promotes Tumor Immunity to Increase the Efficacy of Dual CTLA4 and PD-1 Checkpoint Blockade
Authors: Gao Yaqi , Xu Pingping , Sun Danfeng , Jiang Yi , Lin Xiao-Lin , Han Ting , Yu Jun , Sheng Chunquan , Chen Haoyan , Hong Jie , Chen Yingxuan , Xiao Xiu-Ying , Fang Jing-Yuan
Published: November 2023

Abstract
Immune checkpoint inhibitors (ICI) have revolutionized cancer therapy; however, their application is limited by the occurrence of immune-related adverse events. The gut microbiota plays important roles in the response to and toxicity of immunotherapy and Faecalibacterium prausnitzii (F. prausnitzii) has been shown to possess immunomodulatory potential. Here, we found that patients receiving ICIs who developed colitis had a lower abundance of F. prausnitzii. In vivo, immunocompetent mice administered with dextran sodium sulfate and immunodeficient NSG mice with human peripheral blood mononuclear cell transfer were treated with ICIs to study ICI-induced colitis. Dual CTLA4 and PD-1 blockade exacerbated autoimmune colitis, activated an inflammatory response, and promoted myeloid cell infiltration, with higher percentages of macrophages, dendritic cells, monocytes, and neutrophils. F. prausnitzii administration mitigated the exacerbated colitis induced by ICIs. Concomitantly, F. prausnitzii enhanced the antitumor immunity elicited by ICIs in tumor-bearing mice while abrogating colitis. In addition, administration of F. prausnitzii increased gut microbial alpha diversity and modulated the microbial composition, increasing a subset of gut probiotics and decreasing potential gut pathogens. F. prausnitzii abundance was reduced in mice that developed ICI-associated colitis. Together, this study shows that F. prausnitzii administration ameliorates ICI-induced colitis, reshapes the gut microbial composition, and enhances the antitumor activity of immunotherapy.
Significance:
F. prausnitzii alleviates colitis while enhancing the tumor-suppressive effects of immune checkpoint blockade, indicating that supplementation with F. prausnitzii could be a treatment strategy to mitigate immunotherapy toxicity in patients with cancer.
Data from SETD2 Deficiency Confers Sensitivity to Dual Inhibition of DNA Methylation and PARP in Kidney Cancer
Authors: Zhou Xinyi , Sekino Yohei , Li Hong-Tao , Fu Guanghou , Yang Zhi , Zhao Shuqing , Gujar Hemant , Zu Xiongbing , Weisenberger Daniel J. , Gill Inderbir S. , Tulpule Varsha , D’souza Anishka , Quinn David I. , Han Bo , Liang Gangning
Published: November 2023

Abstract
SETD2 deficiency alters the epigenetic landscape by causing depletion of H3K36me3 and plays an important role in diverse forms of cancer, most notably in aggressive and metastatic clear-cell renal cell carcinomas (ccRCC). Development of an effective treatment scheme targeting SETD2-compromised cancer is urgently needed. Considering that SETD2 is involved in DNA methylation and DNA repair, a combination treatment approach using DNA hypomethylating agents (HMA) and PARP inhibitors (PARPi) could have strong antitumor activity in SETD2-deficient kidney cancer. We tested the effects of the DNA HMA 5-aza-2′-dexoxydytidine (DAC), the PARPi talazoparib (BMN-673), and both in combination in human ccRCC models with or without SETD2 deficiency. The combination treatment of DAC and BMN-673 synergistically increased cytotoxicity in vitro in SETD2-deficient ccRCC cell lines but not in SETD2-proficient cell lines. DAC and BMN-673 led to apoptotic induction, increased DNA damage, insufficient DNA damage repair, and increased genomic instability. Furthermore, the combination treatment elevated immune responses, upregulated STING, and enhanced viral mimicry by activating transposable elements. Finally, the combination effectively suppressed the growth of SETD2-deficient ccRCC in in vivo mouse models. Together, these findings indicate that combining HMA and PARPi is a promising potential therapeutic strategy for treating SETD2-compromised ccRCC.
Significance:
SETD2 deficiency creates a vulnerable epigenetic status that is targetable using a DNA hypomethylating agent and PARP inhibitor combination to suppress renal cell carcinoma, identifying a precision medicine–based approach for SETD2-compromised cancers.
Data from A Cell Surface-Binding Antibody Atlas Nominates a MUC18-Directed Antibody–Drug Conjugate for Targeting Melanoma
Authors: Shi Jing , Jiao Tao , Guo Qian , Weng Weining , Ma Linjie , Zhang Qing , Wang Lijun , Zhang Jianjian , Chen Caiwei , Huang Yaling , Wang Mingqiao , Pan Rong , Tang Yanfang , Hu Wenhao , Meng Tao , Liu Shu-Hui , Guo Jun , Kong Yan , Meng Xun
Published: November 2023

Abstract
Recent advances in targeted therapy and immunotherapy have substantially improved the treatment of melanoma. However, therapeutic strategies are still needed for unresponsive or treatment-relapsed patients with melanoma. To discover antibody–drug conjugate (ADC)–tractable cell surface targets for melanoma, we developed an atlas of melanoma cell surface–binding antibodies (pAb) using a proteome-scale antibody array platform. Target identification of pAbs led to development of melanoma cell killing ADCs against LGR6, TRPM1, ASAP1, and MUC18, among others. MUC18 was overexpressed in both tumor cells and tumor-infiltrating blood vessels across major melanoma subtypes, making it a potential dual-compartment and universal melanoma therapeutic target. AMT-253, an MUC18-directed ADC based on topoisomerase I inhibitor exatecan and a self-immolative T moiety, had a higher therapeutic index compared with its microtubule inhibitor–based counterpart and favorable pharmacokinetics and tolerability in monkeys. AMT-253 exhibited MUC18-specific cytotoxicity through DNA damage and apoptosis and a strong bystander killing effect, leading to potent antitumor activities against melanoma cell line and patient-derived xenograft models. Tumor vasculature targeting by a mouse MUC18-specific antibody–T1000-exatecan conjugate inhibited tumor growth in human melanoma xenografts. Combination therapy of AMT-253 with an antiangiogenic agent generated higher efficacy than single agent in a mucosal melanoma model. Beyond melanoma, AMT-253 was also efficacious in a wide range of MUC18-expressing solid tumors. Efficient target/antibody discovery in combination with the T moiety–exatecan linker–payload exemplified here may facilitate discovery of new ADC to improve cancer treatment.
Significance:
Discovery of melanoma-targeting antibodies using a proteome-scale array and use of a cutting-edge linker–payload system led to development of a MUC18-targeting antibody–exatecan conjugate with clinical potential for treating major melanoma subtypes.
Data from Stroma-Mediated Breast Cancer Cell Proliferation Indirectly Drives Chemoresistance by Accelerating Tumor Recovery between Chemotherapy Cycles
Authors: Miroshnychenko Daria , Miti Tatiana , Kumar Pragya , Miller Anna , Laurie Mark , Giraldo Nathalia , Bui Marilyn M. , Altrock Philipp M. , Basanta David , Marusyk Andriy
Published: November 2023

Abstract
The ability of tumors to survive therapy reflects both cell-intrinsic and microenvironmental mechanisms. Across many cancers, including triple-negative breast cancer (TNBC), a high stroma/tumor ratio correlates with poor survival. In many contexts, this correlation can be explained by the direct reduction of therapy sensitivity induced by stroma-produced paracrine factors. We sought to explore whether this direct effect contributes to the link between stroma and poor responses to chemotherapies. In vitro studies with panels of TNBC cell line models and stromal isolates failed to detect a direct modulation of chemoresistance. At the same time, consistent with prior studies, fibroblast-produced secreted factors stimulated treatment-independent enhancement of tumor cell proliferation. Spatial analyses indicated that proximity to stroma is often associated with enhanced tumor cell proliferation in vivo. These observations suggested an indirect link between stroma and chemoresistance, where stroma-augmented proliferation potentiates the recovery of residual tumors between chemotherapy cycles. To evaluate this hypothesis, a spatial agent–based model of stroma impact on proliferation/death dynamics was developed that was quantitatively parameterized using inferences from histologic analyses and experimental studies. The model demonstrated that the observed enhancement of tumor cell proliferation within stroma-proximal niches could enable tumors to avoid elimination over multiple chemotherapy cycles. Therefore, this study supports the existence of an indirect mechanism of environment-mediated chemoresistance that might contribute to the negative correlation between stromal content and poor therapy outcomes.
Significance:
Integration of experimental research with mathematical modeling reveals an indirect microenvironmental chemoresistance mechanism by which stromal cells stimulate breast cancer cell proliferation and highlights the importance of consideration of proliferation/death dynamics.

See related commentary by Wall and Echeverria, p. 3667
Data from Subclonal Somatic Copy-Number Alterations Emerge and Dominate in Recurrent Osteosarcoma
Authors: Kinnaman Michael D. , Zaccaria Simone , Makohon-Moore Alvin , Arnold Brian , Levine Max F. , Gundem Gunes , Arango Ossa Juan E. , Glodzik Dominik , Rodríguez-Sánchez M. Irene , Bouvier Nancy , Li Shanita , Stockfisch Emily , Dunigan Marisa , Cobbs Cassidy , Bhanot Umesh K. , You Daoqi , Mullen Katelyn , Melchor Jerry P. , Ortiz Michael V. , O'Donohue Tara J. , Slotkin Emily K. , Wexler Leonard H. , Dela Cruz Filemon S. , Hameed Meera R. , Glade Bender Julia L. , Tap William D. , Meyers Paul A. , Papaemmanuil Elli , Kung Andrew L. , Iacobuzio-Donahue Christine A.
Published: November 2023

Abstract
Multiple large-scale genomic profiling efforts have been undertaken in osteosarcoma to define the genomic drivers of tumorigenesis, therapeutic response, and disease recurrence. The spatial and temporal intratumor heterogeneity could also play a role in promoting tumor growth and treatment resistance. We conducted longitudinal whole-genome sequencing of 37 tumor samples from 8 patients with relapsed or refractory osteosarcoma. Each patient had at least one sample from a primary site and a metastatic or relapse site. Subclonal copy-number alterations were identified in all patients except one. In 5 patients, subclones from the primary tumor emerged and dominated at subsequent relapses. MYC gain/amplification was enriched in the treatment-resistant clones in 6 of 7 patients with multiple clones. Amplifications in other potential driver genes, such as CCNE1, RAD21, VEGFA, and IGF1R, were also observed in the resistant copy-number clones. A chromosomal duplication timing analysis revealed that complex genomic rearrangements typically occurred prior to diagnosis, supporting a macroevolutionary model of evolution, where a large number of genomic aberrations are acquired over a short period of time followed by clonal selection, as opposed to ongoing evolution. A mutational signature analysis of recurrent tumors revealed that homologous repair deficiency (HRD)-related SBS3 increases at each time point in patients with recurrent disease, suggesting that HRD continues to be an active mutagenic process after diagnosis. Overall, by examining the clonal relationships between temporally and spatially separated samples from patients with relapsed/refractory osteosarcoma, this study sheds light on the intratumor heterogeneity and potential drivers of treatment resistance in this disease.
Significance:
The chemoresistant population in recurrent osteosarcoma is subclonal at diagnosis, emerges at the time of primary resection due to selective pressure from neoadjuvant chemotherapy, and is characterized by unique oncogenic amplifications.