bluuebunny/crossref_metadata_2025 huggingface dataset:
Exploring barriers and facilitators of primary care physicians towards optimising statin therapy in patients with hyperlipidaemia in the very high-risk group: a qualitative study in Singapore
Authors: Beh Chun Yen , Fok Rose Wai-Yee , Goh Lay Hoon
Published: September 2023

Objectives

To explore the perspectives of primary care physicians with regard to the barriers and facilitators towards optimising statin therapy in patients with hyperlipidaemia in the very high-risk group.

Design

Qualitative descriptive study.

Setting

Four polyclinics in a public primary care institution in Singapore.

Participants

Seven men and five women working as primary care physicians were recruited for in-depth interviews.

Results

The major barriers to statin optimisation identified were patients’ lack of knowledge and awareness, patients’ fear of side effects, negative external influences on patients, poor doctor–patient relationship, time constraint during consultations, physicians’ unfamiliarity with guidelines, low health literacy among the local population and lack of strong national policy. The major facilitators identified were patient education, providing continuity of care, improving electronic medical record systems’ capabilities, physician education and public education.

Conclusion

We identified several important barriers and facilitators of statin therapy optimisation in this study. This information offers insights into the development of a multipronged approach to address barriers across different levels with the aim of optimising statin use, reducing cardiovascular events and improving patient outcomes.
Consensus recommendations on holistic care in hereditary ATTR amyloidosis: an international Delphi survey of patient advocates and multidisciplinary healthcare professionals
Authors: Obici Laura , Callaghan Rosaline , Ablett Joanne , Bibiloni Catilena , Bueser Teofila , Conceição Isabel , Dongiglio Francesca , Farrugia Agnès , Knebel Fabian , Lane Thirusha , Larsson Lars-Ove , Morier Agnès , Nicholas Vincent , Coelho Teresa
Published: September 2023

Background

Hereditary transthyretin-mediated amyloidosis is a rare, progressive and potentially life-limiting multisystem disease, affecting every aspect of a patient’s life.

Objectives

This online international Delphi survey aimed to evolve clinical−patient-led practical guidance, to inspire and encourage a holistic approach to care that is managed in specialist settings by multidisciplinary teams and supported by allied healthcare professionals (HCPs) and patient advocacy groups (PAGs).

Design

A 14-member joint patient advocate−HCP primary panel was convened including representation from PAGs and key clinical specialties (neurology, cardiology, internal medicine, physiotherapy, clinical psychology, dietetics and specialist nursing). Guidance evolved on the care provision needed to support seven core goals: early diagnosis and treatment; disease monitoring and organisation of care; maintenance of physical and mental health; family-centred care and caregiver support; patient−doctor dialogue; access to social support and social networking.

Participants

From June to October 2022, 252 HCPs and 51 PAG representatives from 27 countries were invited to participate in a Delphi survey. Of the 122 respondents who answered at least one survey question, most were HCPs (100, 82%) from specialist centres; the remainder were PAG representatives (22, 18%).

Main outcome measure

Both level of agreement and feasibility in practice of each recommendation was tested by two anonymised online Delphi voting rounds.

Results

Based on an a priori threshold for consensus of ≥75% agreement, the clinical–patient community endorsed all but one recommendation. However, only 17/49 (35%) recommendations were identified by most HCPs as a core part of routine care; the remainder (32/49 (65%)) were identified as part of core care by <50% of HCPs respondents, or as largely achievable by 30%–45% of HCPs. By comparison, PAGs recorded lower implementation levels.

Conclusions

Further consideration is needed on how to evolve multidisciplinary services (supported by allied HCPs and PAGs) to address the complex needs of those affected by this disease.
Where do those experiencing sexual violence seek help and is routine enquiry acceptable within a sexual healthcare setting? Findings from a population-based survey
Authors: Caswell Rachel J , Hodson James , Bradbury-Jones Caroline , Ross Jonathan D C
Published: September 2023

Objectives

Most sexual violence (SV) remains undisclosed to healthcare professionals. The aims of this study were to identify where support would be sought after SV and whether routine enquiry about SV was acceptable in a sexual healthcare setting.

Design

An online population-based survey collected data on a history of SV and preferences on support after SV, in addition to sociodemographic data. Respondents’ views on being routinely asked about SV were sought.

Setting and participants

This online survey was based in England, UK. There were 2007 respondents.

Results

The police were the most frequent first choice for support after experiencing SV (n=520; 25.9%); however, this was less common in individuals in younger age groups (p<0.001) and in those with a history of SV (17.2% vs 29.9%, p<0.001). For the 27.1% (532 of 1960) of respondents who reported a history of SV, the first choice of place for support was Rape Crisis or similar third-sector organisation. The majority of respondents supported routine enquiry about SV during Sexual and Reproductive Health Service (SRHS) consultations (84.4%), although acceptability was significantly lower in older age groups.

Conclusions and study implications

A greater awareness of the influence of sociodemographic factors, including ethnicity, age, gender, disability and a history of SV, when planning and delivering services for those who have experienced SV is needed. A history of SV is common in the general population, and a ‘one-size-fits-all’ approach to encourage disclosure and access to support is unlikely to be optimal. Routine enquiry about SV is highly acceptable in an SRHS setting and likely to improve disclosure when appropriately implemented.
Health systems efficiency in China and ASEAN, 2015–2020: a DEA-Tobit and SFA analysis application
Authors: Kang Jing , Peng Rong , Feng Jun , Wei Junyuan , Li Zhen , Huang Fen , Yu Fu , Su Xiaorong , Chen Yujun , Qin Xianjing , Feng Qiming
Published: September 2023

Objective

To evaluate the health systems efficiency in China and Association of Southeast Asian Nations (ASEAN) countries from 2015 to 2020.

Design

Health efficiency analysis using data envelopment analysis (DEA) and stochastic frontier approach analysis.

Setting

Health systems in China and ASEAN countries.

Methods

DEA-Malmquist model and SFA model were used to analyse the health system efficiency among China and ASEAN countries, and the Tobit regression model was employed to analyse the factors affecting the efficiency of health system among these countries.

Results

In 2020, the average technical efficiency, pure technical efficiency and scale efficiency of China and 10 ASEAN countries’ health systems were 0.700, 1 and 0.701, respectively. The average total factor productivity (TFP) index of the health systems in 11 countries from 2015 to 2020 was 0.962, with a decrease of 1.4%, among which the average technical efficiency index was 1.016, and the average technical progress efficiency index was 0.947. In the past 6 years, the TFP index of the health system in Malaysia was higher than 1, while the TFP index of other countries was lower than 1. The cost efficiency among China and ASEAN countries was relatively high and stable. The per capita gross domestic product (current US$) and the urban population have significant effects on the efficiency of health systems.

Conclusions

Health systems inefficiency is existing in China and the majority ASEAN countries. However, the lower/middle-income countries outperformed high-income countries. Technical efficiency is the key to improve the TFP of health systems. It is suggested that China and ASEAN countries should enhance scale efficiency, accelerate technological progress and strengthen regional health cooperation according to their respective situations.
Randomised, open-label, non-inferiority clinical trial on the efficacy and safety of a 7-day vs 14-day course of antibiotic treatment for uncomplicated enterococcal bacteraemia: the INTENSE trial protocol
Authors: Maldonado Natalia , Rosso-Fernández Clara M , Portillo-Calderón Inés , Borreguero Borreguero Irene , Tristán-Clavijo Enriqueta , Palacios-Baena Zaira R , Salamanca Elena , Fernández-Cuenca Felipe , De-Cueto Marina , Stolz-Larrieu Emilio , Rodriguez-Baño Jesús , López-Cortés Luis Eduardo
Published: September 2023

Introduction

Enterococcusspp is responsible for 8%–15% of total bacteraemias with an associated global mortality around 23%–30%. Regarding the clinical management of enterococcal bacteraemia, the evidence on the duration of antibiotic treatment is scarce and the studies do not discriminate between complicated and uncomplicated bacteraemia.

Methods

The INTENSE study is a multicentre, open-label, randomised, pragmatic, phase-IV clinical trial to demonstrate the non-inferiority of a 7-day vs 14-day course for the treatment of uncomplicated enterococcal bacteraemia and incorporating the early switching to oral antibiotics when feasible. The primary efficacy endpoint is the clinical cure at day 30±2 after the end of the treatment. Secondary endpoints will include the rate of relapse or infective endocarditis, length of stay, duration of intravenous therapy,Clostridioides difficileinfection and the evaluation of the safety of both treatment arms through the recording and analysis of adverse events. For a 6% non-inferiority margin and considering a 5% withdrawal rate, 284 patients will be included.

Analysis

The difference in proportions with one-sided 95% CIs will be calculated for the clinical cure rate using the control group as reference. For secondary categorical endpoints, a similar analysis will be performed and Mann-Whitney U-test will be used to compare median values of quantitative variables. A superiority analysis applying the response adjusted for days of antibiotic risk will be performed if there were incidents in recruitment; will allow obtaining results with 194 patients recruited.

Ethics and dissemination

The study has obtained the authorisation from the Spanish Regulatory Authority, the approval of the ethics committee and the agreement of the directors of each centre. Data will be published in peer-reviewed journals.

Trial registration number

NCT05394298.
Biomarkers in heart failure: a focus on natriuretic peptides
Authors: Eltayeb Mohamed , Squire Iain , Sze Shirley
Published: September 2023

While progress has been made in the management of most aspects of cardiovascular disease, the incidence and prevalence of heart failure (HF) remains high. HF affects around a million people in the UK and has a worse prognosis than most cancers. Patients with HF are often elderly with complex comorbidities, making accurate assessment of HF challenging. A timely diagnosis and initiation of evidence-based treatments are key to prevent hospitalisation and improve outcomes in this population. Biomarkers have dramatically impacted the way patients with HF are evaluated and managed. The most studied biomarkers in HF are natriuretic peptides (NPs). Since their discovery in the 1980s, there has been an explosion of work in the field of NPs and they have become an important clinical tool used in everyday practice to guide diagnosis and prognostic assessment of patients with HF. In this article, we will review the physiology of NPs and study their biological effects. Then, we will discuss the role of NPs in the diagnosis, management and prognostication of patients with HF. We will also explore the role of NPs as a potential therapeutic agent.
Spinal dural and epidural fistulas: role of cone beam CT in diagnosis and treatment
Authors: Shapiro Maksim , Nossek Erez , Sharashidze Vera , Tanaka Michihiro , Rutledge Caleb , Chung Charlotte , Khawaja Ayaz , Riina Howard , Nelson Peter Kim , Raz Eytan
Published: September 2023

Understanding normal spinal arterial and venous anatomy, and spinal vascular disease, is impossible without flow-based methods. Development of practical spinal angiography led to site-specific categorization of spinal vascular conditions, defined by the ‘seat of disease’ in relation to the cord and its covers. This enabled identification of targets for highly successful surgical and endovascular treatments, and guided interpretation of later cross-sectional imaging.

Spinal dural and epidural arteriovenous fistulas represent the most common types of spinal shunts. Although etiology is debated, anatomy provides excellent pathophysiologic correlation. A spectrum of fistulas, from foramen magnum to the sacrum, is now well-characterized.

Most recently, use of cone beam CT angiography has yielded new insights into normal and pathologic anatomy, including venous outflow. It provides unrivaled visualization of the fistula and its relationship with spinal cord vessels, and is the first practical method to study normal and pathologic spinal veins in vivo—with multiple implications for both safety and efficacy of treatments. We advocate consistent use of cone beam CT imaging in modern spinal fistula evaluation.

The role of open surgery is likely to remain undiminished, with increasing availability and use of hybrid operating rooms for practical intraoperative angiography enhancing safety and efficacy of complex surgery.
Fundamental practices for drone remote sensing research across disciplines
Authors: Mathews Adam J. , Singh Kunwar K. , Cummings Anthony R. , Rogers Stephanie R.
Published: September 2023

Drone remote sensing research has surged over the last few decades as the technology has become increasingly accessible. Relatively easy-to-operate drones put data collection directly in the hands of the remote sensing community. While an abundance of remote sensing studies using drones in myriad areas of application (e.g., agriculture, forestry, and geomorphology) have been published, little consensus has emerged regarding best practices for drone usage and incorporation into research. Therefore, this paper synthesizes relevant literature, supported by the collective experiences of the authors, to propose ten fundamental practices for drone remote sensing research, including (1) focus on your question, not just the tool, (2) know the law and abide by it, (3) respect privacy and be ethical, (4) be mindful consumers of technology, (5) develop or adopt a data collection protocol, (6) treat Structure from Motion (SfM) as a new form of photogrammetry, (7) consider new approaches to analyze hyperspatial data, (8) think beyond imagery, (9) be transparent and report error, and (10) work collaboratively. These fundamental practices, meant for all remote sensing researchers using drones regardless of area of interest or disciplinary background, are elaborated upon and situated within the context of broader remote sensing research.
Multidimensional Statistical Convergence in Credibility Theory
Authors: Savaş Rabia
Published: September 2023

The purpose of this article is to present the concepts of double statistical convergence in credibility and [Formula: see text]-double statistical convergence in credibility in pringsheim sense. By using these definitions we present a natural multidimensional extension of Credibility theory via Summability methods.
Instability and bifurcation analysis of a diffusive predator–prey model with fear effect and delay
Authors: Sun Hongyan , Cao Jianzhi , Hao Pengmiao , Zhang Lijie
Published: September 2023

In this paper, a delayed diffusive predator–prey model with fear effect under Neumann boundary conditions is considered. For the system without diffusion and delay, the conditions for the existence and local stability of equilibria are obtained by analyzing the eigenvalues. Then, the instability induced by diffusion and delay-diffusion of the positive constant stationary solutions are discussed, respectively. Moreover, the regions of instability and pattern formation can be achieved with respect to diffusion and delay coefficients. Furthermore, the existence and direction of Hopf bifurcation and the properties of the homogeneous/nonhomogeneous bifurcated periodic solutions are driven by using the center manifold theorem and the normal form theory. Finally, some numerical simulations are carried out to verify the theoretical results.
Anomalous Kinetics of Photoluminescence from Degrading Organic Materials and Its Theoretical Rendition
Authors: Lattanzi A. , Baldacchini G.
Published: September 2023

The Photoluminescence (PL) degradation of thermally evaporated Alq3 thin films is described by four Kohlrausch-Williams-Watt (KWW) functions, which are solely mathematical expressions. The present contribution not only unfolds the physical meaning of the KWW function, but also reveals new mathematical tools. By introducing the concept of the material clock, the system has been described by a damped harmonic oscillator, which in certain conditions allows the expansion of the KWW function in the so-called Prony series. The terms of this series can be attributed to chemical and physical processes that really contribute to the decay, i.e., degradation of Alq3 thin films when interacting with internal and environmental agents. These insights unveiled the usefulness of proper mathematical procedures and properties, such as the monotonicity and the complete monotonicity, for investigating the PL of this ubiquitous organometallic molecule, which possesses one among the highest emission yield. Moreover, this method is also promising for describing the photoluminescent processes of similar organic molecules important both for basic research and optoelectronic applications.
Hydrological Evaluation of the Groundwater Potential in the Fractured Karoo Aquifer Using Magnetic and Electrical Resistivity Methods: Case Study of the Balfour Formation, Alice, South Africa
Authors: Adesola Gbenga Olamide , Gwavava Oswald , Liu Kuiwu
Published: September 2023

The study is aimed at evaluating the groundwater accumulations present in Alice using magnetic and electrical resistivity measurements to examine the trends of structural elements and characterize the groundwater resource for borehole drilling. The magnetic maps show a low magnetic linear structure moving northwest to southeast direction, which may be caused by fractures. The linear high intensities were probably caused by dolerite dykes, while dolerite sills caused broader high-intensity areas. The depth slices show that the near-surface magnetic structures are visible to a depth of about 19 m, and the deep-seated structures are found at a depth of about 31 m, possibly deeper. Twenty-five vertical electrical soundings (VES) of the Schlumberger array were measured with AB/2 varying between 1.5 m and 250 m across the study area. The VES interpretation showed four geoelectric layers composed of HK and HA curve types. The geoelectric layer’s thicknesses are (1) topsoil from 0.4 to 1.8 m, (2) weathered layer from 0.8 to 17.5 m, and (3) weathered/fractured layer from 9.9 to 143.9 m; the third layer could be the productive water-bearing zones, and (4) bedrock layer has an infinite thickness. The layers have resistivity values of 20-5752 Ωm, 3-51 Ωm, 136-352 Ωm, and 44-60428 Ωm, respectively. A correlation of the VES with the borehole log indicated a well-matched result. The magnetic and electrical resistivity surveys provided a detailed subsurface structure and helped identify possible fractures that could act as a passage for groundwater.
Anti-skin Aging Potential of Sargassum thunbergii Ethanolic Extract: Antioxidant, Anti-inflammatory, and Antiwrinkle Effects on L929 Fibroblast Cells
Authors: Cui Lulu , Qu Haidong , Qiao Kun , Liu Shuji , Wu Jingna , Su Yongchang , Chen Bei , Liu Zhiyu
Published: September 2023

Increasing life expectancy of the human population has created a demand for functional food with anti-skin aging properties. Skin aging is a degenerative process caused by oxidative stress, inflammation, and matrix destruction. Some secondary metabolites isolated from marine macroalgae have been shown to exhibit potential dermatological benefits. The present study investigated the skin-protective properties of the ethanolic extract from Sargassum thunbergii (STEE) via antioxidant, anti-inflammatory, and antiwrinkle effects on mouse fibroblast L929 cells. The optimal extraction conditions for STEE were determined as follows: ratio of liquid to solid 25 : 1 mL/g, concentration of ethanol 40.2%, and extraction time 40 min. STEE was further purified by adsorption using a macroporous resin, SP700. STEE exhibited high DPPH radical and hydroxyl scavenging activity in vitro, enhanced the viability of H2O2-treated L929 cells, and reduced intracellular ROS generation in a dose-dependent manner. Superoxide dismutase and glutathione peroxidase activities and total antioxidant capacity in H2O2-treated L929 cells were increased while malondialdehyde content was markedly reduced by pretreatment with STEE. The inhibitory effect of STEE on H2O2-induced inflammation was shown by the downregulation of tumor necrosis factor-α, interleukin-6, cyclooxygenase-2, and inducible nitric oxide synthase. Furthermore, STEE reduced the matrix metalloproteinase-2 expression and inhibited collagenase and elastase activities. Moreover, STEE was nonirritating to human skin at 100 mg/mL according to the in vitro skin irritation test using EpiSkin™. Hemolysis assay showed that the hemolysis EC50 (1275 μg/mL) of STEE is much higher than the maximum effective concentration (125 μg/mL) against H2O2 exposure. Our results demonstrate that STEE may be a good candidate for the development of anti-skin aging functional food and cosmetic products.
Antibacterial Activity of a Phenylpropanoid from the Root Extract of Carduus leptacanthus Fresen
Authors: Dagne Abebe , Degu Sileshi , Abebe Abiy , Bisrat Daniel
Published: September 2023

Background. The emergence and rapid spread of antimicrobial drug-resistance microorganisms exacerbate the treatment of infectious diseases, underscoring the importance of finding new, safe, and effective drugs. In Ethiopia, the roots of Carduus leptacanthus have traditionally been employed to treat microbial infectious diseases The aim of this study was to evaluate the antibacterial activity of the root extract and its primary components against six bacterial strains (Staphylococcus aureus, Staphylococcus epidermidis, Streptococcus agalactiae, Escherichia coli, Pseudomonas aeruginosa, and Klebsiella pneumonia). Methods. The extraction involved maceration of air-dried and powdered roots of C. leptacanthus with 80% methanol. The compound was isolated from the root extract using silica gel column chromatography and recrystallization in CHCl3/MeOH (9 : 1) and was characterized using ESI-MS and 1D-NMR spectroscopy. Antibacterial activity of the extract was assessed using agar well diffusion and broth microdilution methods. Results. Syringin, a phenylpropanoid, was isolated and characterized from the extract of C. leptacanthus. The extract showed the most substantial efficacy against S. epidermidis (MIC = 5.33 mg/ml and inhibition zone diameter of 24 mm at 200 mg/m). Syringin also elicited antibacterial activity against S. aureus (MIC = 13.33 mg/ml), S. epidermidis (MIC = 16 mg/ml), and S. agalactiae (MIC = 16 mg/ml). Despite being tested up to a maximum concentration of 16 mg/ml, syringin did not exhibit antibacterial activity against the Gram-negative bacteria (P. aeruginosa, E. coli, and K. pneumonia). Conclusions. In conclusion, the findings suggest that syringin exhibits partial involvement in the root extract’s antibacterial activity, thereby potentially supporting the traditional medicinal use of the plant.
Node Importance Estimation with Multiview Contrastive Representation Learning
Authors: Liu Li , Zeng Weixin , Tan Zhen , Xiao Weidong , Zhao Xiang
Published: September 2023

Node importance estimation is a fundamental task in graph analysis, which can be applied to various downstream applications such as recommendation and resource allocation. However, existing studies merely work under a single view, which neglects the rich information hidden in other aspects of the graph. Hence, in this work, we propose a Multiview Contrastive Representation Learning (MCRL) model to obtain representations of nodes from multiple perspectives and then infer the node importance. Specifically, we are the first to apply the contrastive learning technique to the node importance analysis task, which enhances the expressiveness of graph representations and lays the foundation for importance estimation. Moreover, based on the improved representations, we generate the entity importance score by attentively aggregating the scores from two different views, i.e., node view and node‐edge interaction view. We conduct extensive experiments on real‐world datasets, and the experimental results show that MCRL outperforms existing methods on all evaluation metrics.
Figure S2 from T Cell–intrinsic Immunomodulatory Effects of TAK-981 (Subasumstat), a SUMO-activating Enzyme Inhibitor, in Chronic Lymphocytic Leukemia
Authors: Lam Vi , Roleder Carly , Liu Tingting , Bruss Nur , Best Scott , Wang Xiaoguang , Phillips Tycel , Shouse Geoffrey , Berger Allison J. , Alinari Lapo , Wang Lili , Siddiqi Tanya , Pennock Nathan D. , Danilov Alexey V.
Published: September 2023

Figure S2 shows Magnetically enriched CD3+ T cells were activated with 0.5 µg/mL αCD3/28 in the presence of TAK-981 or vehicle control for up to 96 h
Supplementary Figure 12 from AMT-562, a Novel HER3-targeting Antibody–Drug Conjugate, Demonstrates a Potential to Broaden Therapeutic Opportunities for HER3-expressing Tumors
Authors: Weng Weining , Meng Tao , Pu Junyi , Ma Linjie , Shen Yi , Wang Zhaohui , Pan Rong , Wang Mingqiao , Chen Caiwei , Wang Lijun , Zhang Jianjian , Zhou Biao , Shao Siyuan , Qian Yu , Liu Shuhui , Hu Wenhao , Meng Xun
Published: September 2023

AMT-562 is more effective as single agent or in combination therapy for colorectal cancer.
Supplementary Figure 11 from AMT-562, a Novel HER3-targeting Antibody–Drug Conjugate, Demonstrates a Potential to Broaden Therapeutic Opportunities for HER3-expressing Tumors
Authors: Weng Weining , Meng Tao , Pu Junyi , Ma Linjie , Shen Yi , Wang Zhaohui , Pan Rong , Wang Mingqiao , Chen Caiwei , Wang Lijun , Zhang Jianjian , Zhou Biao , Shao Siyuan , Qian Yu , Liu Shuhui , Hu Wenhao , Meng Xun
Published: September 2023

In vivo antitumor efficacy of AMT-562 in pancreatic and gastric cancer.
Supplementary Figure 10 from AMT-562, a Novel HER3-targeting Antibody–Drug Conjugate, Demonstrates a Potential to Broaden Therapeutic Opportunities for HER3-expressing Tumors
Authors: Weng Weining , Meng Tao , Pu Junyi , Ma Linjie , Shen Yi , Wang Zhaohui , Pan Rong , Wang Mingqiao , Chen Caiwei , Wang Lijun , Zhang Jianjian , Zhou Biao , Shao Siyuan , Qian Yu , Liu Shuhui , Hu Wenhao , Meng Xun
Published: September 2023

HER3 expression in a panel of CDX/PDX models by immunohistochemistry.
Supplementary Data from A Targeted Thorium-227 Conjugate Demonstrates Efficacy in Preclinical Models of Acquired Drug Resistance and Combination Potential with Chemotherapeutics and Antiangiogenic Therapies
Authors: Zitzmann-Kolbe Sabine , Kristian Alexander , Zopf Dieter , Kamfenkel Claudia , Politz Oliver , Ellingsen Christine , Hilbig Jochen , Juul Mark U. , Fonslet Jesper , Nielsen Carsten H. , Schatz Christoph A. , Bjerke Roger M. , Cuthbertson Alan S. , Mumberg Dominik , Hagemann Urs B.
Published: September 2023

Supplementary Tables and Supplementary Methods
Figure 2 from Upregulation of Somatostatin Receptor Type 2 Improves 177Lu-DOTATATE Therapy in Receptor-Deficient Pancreatic Neuroendocrine Tumor Model
Authors: Sharma Rupali , Earla Bhargav , Baidoo Kwamena E. , Zeiger Martha A. , Madigan James P. , Escorcia Freddy E. , Sadowski Samira M.
Published: September 2023

HDACis increase SSTR2 transcription and protein expression in three NET cell lines. A, BON-1 cells treated with VPA at 2 mmol/L for 48 hours (P = 0.0001) and 72 hours (P = 0.0144) significantly increased SSTR2 mRNA expression. B, BON-1 cells treated with CI-994 at 2.5 μmol/L for 48 hours (P = 0.0001) and 72 hours (P = 0.03), and at 5 μmol/L for 48 hours (P = 0.0001) and 72 hours (P = 0.0001) had a significant increase in SSTR2 expression. C, QGP-1 cells treated with VPA at 2 mmol/L for 72 hours had a significant increase in SSTR2 expression (P = 0.0379). D, QGP-1 cells treated with CI-994 at 5 μmol/L for 48 hours (P = 0.0392) had a significant increase in SSTR2 expression. E, GOT-1 cells treated with CI-994 at 2.5 μmol/L for 48 hours (P = 0.0008) and 72 hours (P = 0.0022) showed a significant increase in SSTR2 expression. F, HDACis VPA and CI-994 increased SSTR2 protein expression in BON-1 cells 1.4- and 2.8-fold, respectively, with a concomitant increase in H3-histone acetylation at 48 hours. G, HDACis VPA and CI-994 increased SSTR2 protein expression in QGP-1 cells 2.18- and 3.48-fold, respectively, with a concomitant increase in histone acetylation at 48 hours. H, Graphical representation of the FC in total SSTR2 protein expression in BON-1 and QGP-1 cells. Data are expressed as mean ± SEM, (n = 3). *, P < 0.05; **, P < 0.01; ***, P < 0.001; ****, P < 0.0001.
Supplementary Figure 2 from FOXN Transcription Factors: Regulation and Significant Role in Cancer
Authors: Song Jiali , Li Longshan , Fang Yang , Lin Yue , Wu Luojia , Wan Wei , Wei Gen , Hua Fuzhou , Ying Jun
Published: September 2023

Supplementary Figure 2
Table S3 from Pan-Cancer Pharmacogenomic Analysis of Patient-Derived Tumor Cells Using Clinically Relevant Drug Exposures
Authors: Chang Stephen H. , Ice Ryan J. , Chen Michelle , Sidorov Maxim , Woo Rinette W.L. , Rodriguez-Brotons Aida , Jian Damon , Kim Han Kyul , Kim Angela , Stone David E. , Nazarian Ari , Oh Alyssia , Tranah Gregory J. , Nosrati Mehdi , de Semir David , Dar Altaf A. , Desprez Pierre-Yves , Kashani-Sabet Mohammed , Soroceanu Liliana , McAllister Sean D.
Published: September 2023

Supplementary Table 3 binarization sensitivity 19 drugs
Supplementary Data Figure S3 from Pan-Cancer Pharmacogenomic Analysis of Patient-Derived Tumor Cells Using Clinically Relevant Drug Exposures
Authors: Chang Stephen H. , Ice Ryan J. , Chen Michelle , Sidorov Maxim , Woo Rinette W.L. , Rodriguez-Brotons Aida , Jian Damon , Kim Han Kyul , Kim Angela , Stone David E. , Nazarian Ari , Oh Alyssia , Tranah Gregory J. , Nosrati Mehdi , de Semir David , Dar Altaf A. , Desprez Pierre-Yves , Kashani-Sabet Mohammed , Soroceanu Liliana , McAllister Sean D.
Published: September 2023

Figure S3
Supplementary Data Figure S1 from Pan-Cancer Pharmacogenomic Analysis of Patient-Derived Tumor Cells Using Clinically Relevant Drug Exposures
Authors: Chang Stephen H. , Ice Ryan J. , Chen Michelle , Sidorov Maxim , Woo Rinette W.L. , Rodriguez-Brotons Aida , Jian Damon , Kim Han Kyul , Kim Angela , Stone David E. , Nazarian Ari , Oh Alyssia , Tranah Gregory J. , Nosrati Mehdi , de Semir David , Dar Altaf A. , Desprez Pierre-Yves , Kashani-Sabet Mohammed , Soroceanu Liliana , McAllister Sean D.
Published: September 2023

Figure S1
Supplementary Video S4 from Dynamic Glycoprotein Hyposialylation Promotes Chemotherapy Evasion and Metastatic Seeding of Quiescent Circulating Tumor Cell Clusters in Breast Cancer
Authors: Dashzeveg Nurmaa K. , Jia Yuzhi , Zhang Youbin , Gerratana Lorenzo , Patel Priyam , Shajahan Asif , Dandar Tsogbadrakh , Ramos Erika K. , Almubarak Hannah F. , Adorno-Cruz Valery , Taftaf Rokana , Schuster Emma J. , Scholten David , Sokolowski Michael T. , Reduzzi Carolina , El-Shennawy Lamiaa , Hoffmann Andrew D. , Manai Maroua , Zhang Qiang , D'Amico Paolo , Azadi Parastoo , Colley Karen J. , Platanias Leonidas C. , Shah Ami N. , Gradishar William J. , Cristofanilli Massimo , Muller William A. , Cobb Brian A. , Liu Huiping
Published: September 2023

Supplementary Video S4 shows the clustering video of ST6OE cells presented in Fig.2B
Supplementary Data Figures from A Novel Autologous CAR-T Therapy, YTB323, with Preserved T-cell Stemness Shows Enhanced CAR T-cell Efficacy in Preclinical and Early Clinical Development
Authors: Dickinson Michael J. , Barba Pere , Jäger Ulrich , Shah Nirav N. , Blaise Didier , Briones Javier , Shune Leyla , Boissel Nicolas , Bondanza Attilio , Mariconti Luisa , Marchal Anne-Laure , Quinn David S. , Yang Jennifer , Price Andrew , Sohoni Akash , Treanor Louise M. , Orlando Elena J. , Mataraza Jennifer , Davis Jaclyn , Lu Darlene , Zhu Xu , Engels Boris , Moutouh-de Parseval Laure , Brogdon Jennifer L. , Moschetta Michele , Flinn Ian W.
Published: September 2023

Supplementary Fig. S1. Preclinical evaluation and characterization of YTB323 and CTL*019 for Donor 2 and 3; Supplementary Fig. S2. Differential gene expression of CTL*019 cells versus YTB323 cells (preclinical); Supplementary Fig. S3. Preclinical validation of YTB323; Supplementary Fig. S4. Dose-dependent expansion (Cmax and AUC0-21d) of YTB323 and CTL*019 in NSG mice with NALM6; Supplementary Fig. S5. CD4:CD8 ratio comparison of leukapheresis and cell products of YTB323 and tisagenlecleucel; Supplementary Fig. S6. Stemness and memory differentiation gene signatures are retained or enriched for in YTB323 final product; Supplementary Fig. S7. Differential gene expression of tisagenlecleucel versus YTB323 final product; Supplementary Fig. S8. Naive/TSCM cells and a naive stem-like gene signature correlate with higher expansion and a better response; Supplementary Fig. S9. T-cell subset and checkpoint inhibitor analysis by flow cytometry on PBMCs collected post-YTB323 infusion; Supplementary Fig. S10. Pre-clinical T-cell gating strategies.
Supplementary Video S11 from Dynamic Glycoprotein Hyposialylation Promotes Chemotherapy Evasion and Metastatic Seeding of Quiescent Circulating Tumor Cell Clusters in Breast Cancer
Authors: Dashzeveg Nurmaa K. , Jia Yuzhi , Zhang Youbin , Gerratana Lorenzo , Patel Priyam , Shajahan Asif , Dandar Tsogbadrakh , Ramos Erika K. , Almubarak Hannah F. , Adorno-Cruz Valery , Taftaf Rokana , Schuster Emma J. , Scholten David , Sokolowski Michael T. , Reduzzi Carolina , El-Shennawy Lamiaa , Hoffmann Andrew D. , Manai Maroua , Zhang Qiang , D'Amico Paolo , Azadi Parastoo , Colley Karen J. , Platanias Leonidas C. , Shah Ami N. , Gradishar William J. , Cristofanilli Massimo , Muller William A. , Cobb Brian A. , Liu Huiping
Published: September 2023

Supplementary Video S11 shows the clustering video of siECE1 transfected ST6KO cells presented in Fig.5E.
Supplementary Video S1 from Dynamic Glycoprotein Hyposialylation Promotes Chemotherapy Evasion and Metastatic Seeding of Quiescent Circulating Tumor Cell Clusters in Breast Cancer
Authors: Dashzeveg Nurmaa K. , Jia Yuzhi , Zhang Youbin , Gerratana Lorenzo , Patel Priyam , Shajahan Asif , Dandar Tsogbadrakh , Ramos Erika K. , Almubarak Hannah F. , Adorno-Cruz Valery , Taftaf Rokana , Schuster Emma J. , Scholten David , Sokolowski Michael T. , Reduzzi Carolina , El-Shennawy Lamiaa , Hoffmann Andrew D. , Manai Maroua , Zhang Qiang , D'Amico Paolo , Azadi Parastoo , Colley Karen J. , Platanias Leonidas C. , Shah Ami N. , Gradishar William J. , Cristofanilli Massimo , Muller William A. , Cobb Brian A. , Liu Huiping
Published: September 2023

Supplementary Video S1 shows the clustering video of SNA high cells presented in Fig.2A.
Supplementary Figures S1-S18 from FH Variant Pathogenicity Promotes Purine Salvage Pathway Dependence in Kidney Cancer
Authors: Wilde Blake R. , Chakraborty Nishma , Matulionis Nedas , Hernandez Stephanie , Ueno Daiki , Gee Michayla E. , Esplin Edward D. , Ouyang Karen , Nykamp Keith , Shuch Brian , Christofk Heather R.
Published: September 2023

Supplementary Fig. S1: Analysis of FH variants and their associated interpretations of pathogenicity. Supplementary Fig. S2: Kinetic parameters for active/partially-active VUS/CI. Supplementary Fig. S3: Recombinant FH produced for 74 VUS/CI. Supplementary Fig. S4: Michaelis-Menten graphs for VUS/CI incubated with fumarate. Supplementary Fig. S5: Michaelis-Menten graphs for VUS/CI incubated with malate. Supplementary Fig. S6: Broad analysis of recombinant FH. Supplementary Fig. S7: Multimerization status of 74 VUS/CI. Supplementary Fig. S8: Tetramerization correlates with catalytic activity. Supplementary Fig. S9: Expression of FH variants in HLRCC cells. Supplementary Fig. S10: Fumarate accumulation decreases TCA intermediates. Supplementary Fig. S11: FH loss enhances de novo glutathione biosynthesis. Supplementary Fig. S12: Coessentiality of FH and nucleotide biosynthesis genes. Supplementary Fig. S13: Loss of FH activity disrupts de novo purine biosynthesis. Supplementary Fig. S14: Dysregulated purine metabolism is independent of HLRCC cell proliferation rate. Supplementary Fig. S15: FH-deficient cells use the purine salvage pathway to maintain purine nucleotide levels. Supplementary Fig. S16: Pyrimidine metabolism in FH-deficient and FH-expressing cells. Supplementary Fig. S17: Disrupting expression of purine salvage enzymes impairs tumor growth. Supplementary Fig. S18: Purine salvage inhibitor 6-mercaptopurine (6-MP) impairs tumor growth.
Figure 5 from Resistance to Selective FGFR Inhibitors in FGFR-Driven Urothelial Cancer
Authors: Facchinetti Francesco , Hollebecque Antoine , Braye Floriane , Vasseur Damien , Pradat Yoann , Bahleda Rastislav , Pobel Cédric , Bigot Ludovic , Déas Olivier , Florez Arango Juan David , Guaitoli Giorgia , Mizuta Hayato , Combarel David , Tselikas Lambros , Michiels Stefan , Nikolaev Sergey I. , Scoazec Jean-Yves , Ponce-Aix Santiago , Besse Benjamin , Olaussen Ken A. , Loriot Yohann , Friboulet Luc
Published: September 2023

Synergistic effect of combinatorial treatments in patient-derived models of FGFR-driven urothelial cancer. A, In an MR86 PDX, combined erdafitinib–pictilisib (PI3K inhibitor) administration had synergistic effects leading to prolonged inhibition of tumor growth. B, Protein extracts from the MR15 cell line subjected to a phospho-RTK array revealed EGFR activation. C and D, Concomitant EGFR and FGFR inhibition with gefitinib and erdafitinib was synergic both in viability assays (C) and in immunoblot analyses (D). E, The in vivo pharmacologic experiment in the corresponding PDX confirmed the efficiency of the combined treatment strategy.
FGFR Inhibition: Understanding and Overcoming Resistance
Authors: Tripathi Abhishek , Li Daneng , Pal Sumanta K.
Published: September 2023

Facchinetti and colleagues provide key insights into the evolution of resistance to fibroblast growth factor receptor (FGFR) inhibitors, including the development of kinase domain mutations and activation of the PI3K–AKT signaling axis. In a separate study, Subbiah and colleagues report extensive preclinical data and initial clinical data for RLY-4008, an FGFR2-selective inhibitor that is poised to minimize toxicity and overcome resistance through greater potency and selectivity.

See related article by Facchinetti et al., p. 1998 (5).

See related article by Subbiah et al., p. 2012 (7).
Table S1 from Single-cell Profiling Uncovers a Muc4-Expressing Metaplastic Gastric Cell Type Sustained by Helicobacter pylori-driven Inflammation
Authors: O'Brien Valerie P. , Kang Yuqi , Shenoy Meera K. , Finak Greg , Young William C. , Dubrulle Julien , Koch Lisa , Rodriguez Martinez Armando E. , Williams Jeffery , Donato Elizabeth , Batra Surinder K. , Yeung Cecilia C.S. , Grady William M. , Koch Meghan A. , Gottardo Raphael , Salama Nina R.
Published: September 2023

Description of the mouse samples used for single-cell RNA-sequencing.
FIGURE 1 from Single-cell Profiling Uncovers a Muc4-Expressing Metaplastic Gastric Cell Type Sustained by Helicobacter pylori-driven Inflammation
Authors: O'Brien Valerie P. , Kang Yuqi , Shenoy Meera K. , Finak Greg , Young William C. , Dubrulle Julien , Koch Lisa , Rodriguez Martinez Armando E. , Williams Jeffery , Donato Elizabeth , Batra Surinder K. , Yeung Cecilia C.S. , Grady William M. , Koch Meghan A. , Gottardo Raphael , Salama Nina R.
Published: September 2023

Gastric scRNA-seq reveals expansion of pit cell populations in Hp+KRAS+ mice. A, Overview and experimental timeline for mouse experiments, created with BioRender.com. TMX, tamoxifen. B–F, Mice ± Hp infection and ± constitutively active KRAS induction were used for gastric scRNA-seq. Corpus single-cell suspensions were prepared from: one Hp−KRAS+ and one Hp+KRAS+ mouse at 6 weeks; and at 12 weeks, three Hp−KRAS− and two Hp+KRAS− (each pooled into one sample), one individual (never cryopreserved) and two pooled Hp−KRAS+ mice, and one individual (never cryopreserved) and two pooled Hp+KRAS+ mice. B, Cluster analyses followed by UMAP visualization of the entire dataset yielded 25 clusters, including epithelial and immune cell types, which were manually annotated on the basis of gene expression. Endocrine, enteroendocrine cell; cDC, conventional dendritic cell; RBC, erythrocyte/reticulocyte; pDC, plasmacytoid dendritic cell. C, Cells from the 12 week timepoint in the central epithelial cell megacluster, outlined with the dotted line in B, were subjected to reclustering followed by UMAP visualization, yielding 14 clusters that were manually annotated on the basis of gene expression. D, The normalized expression of marker genes for the indicated gastric epithelial cell types is shown for the 14 epithelial clusters from UMAP #2 in C. E, The estimated proportion of each of the 14 epithelial clusters detected in the pilot scRNA-seq experiment in the indicated treatment groups at 12 weeks is shown (rows add to 100%). ND, cell cluster was not detected in the indicated treatment group. F, The distribution of pit cell clusters within each treatment group in E is shown.
Table S1 from Clinical Benefit of Autologous Stem Cell Transplantation for Patients with Multiple Myeloma Achieving Undetectable Minimal Residual Disease after Induction Treatment
Authors: Liu Jiahui , Yan Wenqiang , Fan Huishou , Xu Jingyu , Li Lingna , Du Chenxing , Mao Xuehan , Yan Yuting , Xu Yan , Sui Weiwei , Deng Shuhui , Yi Shuhua , Anderson Kenneth C. , Qiu Lugui , Zou Dehui , An Gang
Published: September 2023

Patient Characteristics, Treatments, and MRD detective methods: ASCT vs. Non-ASCT
Figure S1 from Clinical Benefit of Autologous Stem Cell Transplantation for Patients with Multiple Myeloma Achieving Undetectable Minimal Residual Disease after Induction Treatment
Authors: Liu Jiahui , Yan Wenqiang , Fan Huishou , Xu Jingyu , Li Lingna , Du Chenxing , Mao Xuehan , Yan Yuting , Xu Yan , Sui Weiwei , Deng Shuhui , Yi Shuhua , Anderson Kenneth C. , Qiu Lugui , Zou Dehui , An Gang
Published: September 2023

The workflow of patient selection in this study.
FIGURE 4 from Clinical Benefit of Autologous Stem Cell Transplantation for Patients with Multiple Myeloma Achieving Undetectable Minimal Residual Disease after Induction Treatment
Authors: Liu Jiahui , Yan Wenqiang , Fan Huishou , Xu Jingyu , Li Lingna , Du Chenxing , Mao Xuehan , Yan Yuting , Xu Yan , Sui Weiwei , Deng Shuhui , Yi Shuhua , Anderson Kenneth C. , Qiu Lugui , Zou Dehui , An Gang
Published: September 2023

Impact of longitudinal MRD status before and after ASCT on prognosis: impact of MRD status at ASCT+3 on PFS (A), the impact of MRD status at ASCT+3 on OS (B); the distribution of different MRD status before and after ASCT (C); impact of longitudinal MRD status conversion on PFS (D); impact of longitudinal MRD status conversion on OS (E). ASCT: autologous stem-cell transplant; NR: not reached; NS: not significant; OS: overall survival; PFS: progression-free survival; *, P < 0.05; **, P < 0.01; ***, P < 0.001.
FIGURE 3 from Clinical Benefit of Autologous Stem Cell Transplantation for Patients with Multiple Myeloma Achieving Undetectable Minimal Residual Disease after Induction Treatment
Authors: Liu Jiahui , Yan Wenqiang , Fan Huishou , Xu Jingyu , Li Lingna , Du Chenxing , Mao Xuehan , Yan Yuting , Xu Yan , Sui Weiwei , Deng Shuhui , Yi Shuhua , Anderson Kenneth C. , Qiu Lugui , Zou Dehui , An Gang
Published: September 2023

The impact of ASCT on MRD status duration among early MRD-negative patients: impact of ASCT on MRD-negative status duration (A); multivariate analysis for MRD-negative duration (B); impact of continued MRD-negative status (≥2 years) on OS (C); the impact of ASCT on the proportion of continued MRD-negative status (≥2 years) by different molecular risk groups (D). All: early MRD-negative cohort; ASCT: autologous stem-cell transplant; HR: high-risk cohort; OS: overall survival; SR: standard risk cohort; UHR: ultra-high-risk cohort.
FIGURE 2 from Clinical Benefit of Autologous Stem Cell Transplantation for Patients with Multiple Myeloma Achieving Undetectable Minimal Residual Disease after Induction Treatment
Authors: Liu Jiahui , Yan Wenqiang , Fan Huishou , Xu Jingyu , Li Lingna , Du Chenxing , Mao Xuehan , Yan Yuting , Xu Yan , Sui Weiwei , Deng Shuhui , Yi Shuhua , Anderson Kenneth C. , Qiu Lugui , Zou Dehui , An Gang
Published: September 2023

Subgroup analyses for impact of ASCT among early MRD-negative patients on PFS (A), OS (B). Abnormal LDH level: >247 U/L; ASCT: autologous stem cell transplant; early MRD-negative: achieving MRD-negative after induction treatment; HR: high-risk; HRCAs: high-risk cytogenetic abnormalities, including Del(17p), t(4;14), t(14;16), or Gain 1q; ISS: International Staging System; OS: overall survival; PFS: progression-free survival; SR: standard risk; UHR: ultra-high-risk.
Data from Clinical Benefit of Autologous Stem Cell Transplantation for Patients with Multiple Myeloma Achieving Undetectable Minimal Residual Disease after Induction Treatment
Authors: Liu Jiahui , Yan Wenqiang , Fan Huishou , Xu Jingyu , Li Lingna , Du Chenxing , Mao Xuehan , Yan Yuting , Xu Yan , Sui Weiwei , Deng Shuhui , Yi Shuhua , Anderson Kenneth C. , Qiu Lugui , Zou Dehui , An Gang
Published: September 2023

Attaining undetectable minimal residual disease (MRD) is the current therapeutic goal for multiple myeloma. But there is a current lack of data regarding the clinical benefit of autologous stem cell transplantation (ASCT) for patients with myeloma achieving early MRD-negative status after induction treatment, in addition to the interaction of longitudinal MRD status with ASCT. The current study included 407 patients with transplant-eligible multiple myeloma with available MRD status from the National Longitudinal Cohort of Hematological Diseases in China (NCT04645199), of whom 147 (34.4%) achieved early undetectable MRD and 182 (44.7%) received ASCT. Early MRD-negative status was associated with a lower risk of disease progression [HR = 0.447; 95% confidence interval (CI), 0.333–0.600; P < 0.001] and death (HR = 0.473; 95% CI, 0.320–0.700; P < 0.001). Of note, patients who achieved undetectable MRD early still benefitted from ASCT, with a remarkable improvement in the median MRD-negative duration (33.5–58.0 months, P < 0.001), progression-free survival (PFS; 46.0–88.3 months, P < 0.001), and overall survival (OS; 76.4 months to not reached, P = 0.003). These clinical benefits were more pronounced in patients with aggressive features (high-risk cytogenetic abnormalities or high tumor burden) compared with standard-risk patients. Similar results were observed in patients with detectable MRD after induction treatment. In addition, we identified four MRD-status transformation patterns following ASCT, which were strongly correlated with diverse survival outcomes (P < 0.001). Our study revealed the enhanced clinical significance of ASCT in patients with transplant-eligible myeloma, regardless of early MRD status, particularly for high-risk patients. Subsequent prospective trials are essential to validate these observations.
Significance:
Achieving and maintaining undetectable MRD is the current treatment goal for multiple myeloma. Our results emphasized the remarkable clinical benefit of ASCT on MRD-negative duration, PFS, and OS in patients with multiple myeloma regardless of early MRD status. These favorable impacts were more evident in patients with aggressive features. Importantly, dynamic MRD monitoring among ASCT could facilitate personalized stratification of therapeutic approaches.