bluuebunny/crossref_metadata_2025 huggingface dataset:
Contextualized Knowledge Graph Embedding for Explainable Talent Training Course Recommendation
Authors: Yang Yang , Zhang Chubing , Song Xin , Dong Zheng , Zhu Hengshu , Li Wenjie
Published: August 2023

Learning and development, or L&D, plays an important role in talent management, which aims to improve the knowledge and capabilities of employees through a variety of performance-oriented training activities. Recently, with the rapid development of enterprise management information systems, many research efforts and industrial practices have been devoted to building personalized employee training course recommender systems. Nevertheless, a widespread challenge is how to provide explainable recommendations with the consideration of different learning motivations from talents. To this end, we propose CKGE, a contextualized knowledge graph (KG) embedding approach for developing an explainable training course recommender system. A novel perspective of CKGE is to integrate both the contextualized neighbor semantics and high-order connections as motivation-aware information for learning effective representations of talents and courses. Specifically, in CKGE, for each entity pair (i.e., the talent-course pair), we first construct a meta-graph, including the neighbors of each entity and the meta-paths between entities as motivation-aware information. Then, we develop a novel KG-based Transformer, which can serialize entities and paths in the meta-graph as a sequential input, with the specially designed relational attention and structural encoding mechanisms to better model the global dependence of KG structured data. Meanwhile, the local path mask prediction can effectively reveal the importance of different paths. As a result, CKGE not only can make precise predictions but also can discriminate the saliencies of meta-paths in characterizing corresponding preferences. Extensive experiments on real-world and public datasets clearly validate the effectiveness and interpretability of CKGE compared with state-of-the-art baselines.
Large Old World Fruit Bats on the Brink of Extinction: Causes and Consequences
Authors: Kingston Tigga , Florens F.B. Vincent , Vincenot Christian E.
Published: August 2023

Large Old World fruit bats (LOWFBs), species of Pteropus, Acerodon, and related genera of large bats in the pteropodid subfamily Pteropodinae, play important roles as agents of dispersal and pollination across the Paleotropics. LOWFBs are also collectively the most threatened group of bats in the world, with 71% of extant species assessed as threatened by International Union for Conservation of Nature. As highlighted here, contrary to other bats, the vast majority of LOWFBs face multiple simultaneous threats. Most importantly, biological and ecological traits, in particular life history characteristics, diet, movement, social ecology, and physiology, intensify threats and accelerate species declines. Furthermore, we demonstrate that LOWFBs are to be considered keystone species and express concern about the erosion of this role and the cascading effects expected on native ecosystems. In response to this alarming situation, we advance general recommendations and identify overarching research and conservation actions.
Asymmetric Stem Cell Division and Germline Immortality
Authors: Yamashita Yukiko M.
Published: August 2023

Germ cells are the only cell type that is capable of transmitting genetic information to the next generation, which has enabled the continuation of multicellular life for the last 1.5 billion years. Surprisingly little is known about the mechanisms supporting the germline's remarkable ability to continue in this eternal cycle, termed germline immortality. Even unicellular organisms age at a cellular level, demonstrating that cellular aging is inevitable. Extensive studies in yeast have established the framework of how asymmetric cell division and gametogenesis may contribute to the resetting of cellular age. This review examines the mechanisms of germline immortality—how germline cells reset the aging of cells—drawing a parallel between yeast and multicellular organisms.
Glycerol Electrooxidation at Industrially Relevant Current Densities Using Electrodeposited PdNi/Nifoam Catalysts in Aerated Alkaline Media
Authors: White Jai , Peters Laurent , Martín-Yerga Daniel , Terekhina Irina , Anil Athira , Lundberg Helena , Johnsson Mats , Salazar-Alvarez Germán , Henriksson Gunnar , Cornell Ann
Published: August 2023

Through glycerol electrooxidation, we demonstrate the viability of using a PdNi catalyst electrodeposited on Ni foam to facilitate industrially relevant rates of hydrogen generation while concurrently providing valuable organic chemicals as glycerol oxidation products. This electrocatalyst, in a solution of 2 M NaOH and 1 M glycerol at 80 °C, enabled current densities above 2000 mA cm−2 (in a voltammetric sweep) to be obtained in atmospheres of both air and N2. Repeated potential cycling under an aerated atmosphere to these exceptional current densities indicated a high stability of the catalyst. Through steady state polarisation curves, 1000 mA cm−2 was reached below an anodic potential of 0.8 V vs RHE. Chronoamperometry showed glycerate and lactate being the major oxidation products, with increased selectivity for lactate at the expense of glycerate in aerated systems. Aerated atmospheres were demonstrated to consistently increase the apparent Faradaic efficiency to >100%, as determined by the concentration of oxidation products in solution. The excellent performance of PdNi/Ni in aerated solutions suggests that O2 removal from the electrolyte is not needed for an industrial glycerol electrooxidation process, and that combining electrochemical and chemical glycerol oxidation, in the presence of dissolved O2, presents an important process advantage.
Pattern of Uveitis in a Tertiary Hospital in North Jordan and the Impact of Behcet’s Disease
Authors: Alawneh Khaldoon M. , Saleh Omar A. , Smadi Mahmoud M. , Ababneh Fatima Kamel , Ali Mahmoud Ikhlas Hamed , Smadi Areje M. , Alawneh Diala
Published: August 2023

Aim. The purpose of this study is to assess the prevalence of autoimmune‐mediated uveitis in relation to other diseases and to describe the clinical patterns of uveitis in a single tertiary hospital in north Jordan. Methods. A cross‐sectional retrospective review was performed. We included all patients diagnosed with uveitis in King Abdullah University Hospital (KAUH) ophthalmology clinic and/or patients referred to KAUH rheumatology clinics for evaluation of suspected autoimmune mediated uveitis or for difficult to treat uveitis. This included patients from January 2015 to January 2019. Data collected about patients’ age, sex, anatomical location of the disease, etiology, treatment, complications, and outcomes on vision loss were analyzed. Results. A total of 221 patients were included in our study. The mean (±SD) age was 36 (±16) years. A total of 111 patients were female and 110 were male with a ratio of 1 : 1. Noninfectious uveitis was found to be more common than infectious uveitis (95% vs. 5% respectively). Autoimmune‐mediated uveitis accounted for 40% of the total cases. The most common causes of autoimmune‐mediated uveitis included Behcet’s disease (n = 41, 19%) and seronegative spondyloarthropathy (n = 29, 13%). The majority of patients (n = 207, 94%) were treated with ophthalmic eye drops, cDMARDs (n = 101, 46%), biologics (n = 33, 15%), and colchicine (n = 30, 14%). Conclusion. Autoimmune‐mediated uveitis, most commonly associated with Behcet’s disease and seronegative spondyloarthropathy, represents a high percentage of uveitis in our area. This implies the need for a high index of suspicion at the time of evaluation.
Young Allis Shad Alosa alosa (Clupeidae) Would Not Be Euryphagous: An Assessment of Juvenile Diet and Prey Selectivity under Riverine-Type Conditions
Authors: Baumann Loïc , Aries Adrien , Vedrenne Jacky , Philip Joris , Moreira Sylvia , Bouyssonnie William , Bardonnet Agnès , Acolas Marie-Laure
Published: August 2023

Allis shad Alosa alosa hatches and develops in freshwater before migrating to the sea during its first months of life. Some field research works dedicated to the diet of the species in freshwater put forward that young stages of allis shad feed mainly on zooplankton, being opportunistic and euryphagous; their diet would diversify through ontogeny in relation to growth. However, these assumptions have never been confronted to the availability of prey, and the exact age of fish was unknown. In this work, we reared young allis shad under seminatural conditions, from 6 to 10 days posthatching until nearly 3 months old, in a trophic environment representative of a natural river. The rearing structures were designed as artificial rivers, supplied continuously by natural riverine water and zooplankton prey. Additional zooplankton was produced in separate basins and added daily in the structures. One artificial river was used to rear allis shad in 2018, and the experiment was conducted on two allis shad batches in 2019 (one batch per river). We described the nekton communities of potential prey available for allis shad in the rearing structures by sampling the water every week, and we compared these data with the stomach contents of fish captured at one and two months old posthatching to describe their diet and prey selectivity. Our results suggest that young allis shad should not be considered as opportunistic in their feeding, since clear selectivity was observed at both ages. One-month-old allis shad highly selected cladocerans, probably because they are easy to catch for fish at this age, when their swimming abilities are limited. Feeding selection at two months old drifted towards other prey taxa (dipteran larvae, ostracods, and/or copepods), whereas cladocerans were no longer preferred. Our results suggest that fish density and competition may entice two-month-old allis shad to enlarge their diet to other taxa, including benthic organisms, while one-month-old fish do not seem able to shift their diet and would fast in the absence of cladocerans. Thus, this highlights that the feeding of young allis shad may be highly challenging during their first month of growth.
Drug-Coated Balloon-Only Strategy for De Novo Coronary Artery Disease: A Meta-analysis of Randomized Clinical Trials
Authors: Zhang Wenyi , Zhang Mingduo , Tian Jinfan , Zhang Min , Zhou Yuan , Song Xiantao
Published: August 2023

Backgrounds. Many clinical trials have demonstrated the value of drug-coated balloons (DCB) for in-stent restenosis. However, their role in de novo lesions is not well documented. The aim of this study is to evaluate the safety and efficacy of the DCB-only strategy compared to other percutaneous coronary intervention strategies for de novo coronary lesions. Methods. The PubMed, Embase, Web of Science, and Cochrane Library Central Register of Controlled Trials (CENTRAL) electronic databases were searched for randomized controlled trials published up to May 6, 2023. The primary outcomes were major adverse cardiac events and late lumen loss. Results. A total of eighteen trials with 3336 participants were included. Compared with drug-eluting stents, the DCB-only strategy was associated with a similar risk of major adverse cardiac events (risk ratio

RR

=
0.90

; 95% confidence interval (CI): 0.59 to 1.37,

P
=
0.631

) and a significant decrease in late lumen loss (standardized mean difference

SMD

=
−
0.29

, 95% CI: −0.53 to −0.04,

P
=
0.021

). This effect was consistent in subgroup analysis regardless of indication, follow-up time, drug-eluting stent type, and dual antiplatelet therapy duration. However, DCBs were inferior to DESs for minimum lumen diameter and percentage diameter stenosis. The DCB-only strategy showed significantly better outcomes for most endpoints compared to plain-old balloon angioplasty or bare metal stents. Conclusions. Interventions with a DCB-only strategy are comparable to those of drug-eluting stents and superior to plain-old balloon angioplasty or bare metal stents for the treatment of selected de novo coronary lesions. Additional evidence is still warranted to confirm the value of DCB before widespread clinical utilization can be recommended.
The Interactive Relationship between the Positive Coping Style and Life Quality of Survivors of Pancreatic Cancer and Their Main Family Caregivers Based on the Dyadic Perspective: An Actor-Partner Interdependence Model
Authors: Liu Linglong , Chen Mingxia , Liu Changying , Li Jiarong , Su Wang , Fang Xiaoping
Published: August 2023

Objective. To analyze the interaction of positive coping style and quality of life (QoL) between survivors of pancreatic cancer and their family caregivers based on the Conceptual Framework of Caring Experience of Cancer Family and Actor-Partner Interdependence Model (APIM). Methods. This study adopted a cross-sectional design that selected 200 pairs of survivors of pancreatic cancer and their family caregivers hospitalized in the First and Second Affiliated Hospitals of Nanjing Medical University from August 2020 to February 2021. Survivors of pancreatic cancer and their family caregivers completed Simple Coping Style Questionnaire and 12-item Short-Form Health Survey, whose results successfully built an APIM model. Results. The spousal relationship was the most common type of dyadic relationship. Family caregivers had higher levels of positive coping and QoL than cancer survivors. In terms of actor effects, the positive coping style of both survivors and caregivers significantly affected individual total scores of QoL and personal physical and psychological dimensions of QoL. As for the partner effects, the positive coping style of both survivors and caregivers significantly impacted their partners’ total QoL scores and the positive coping style of survivors significantly impacted their caregivers’ psychological level of QoL. Conclusions. The positive coping style of survivors of pancreatic cancer affects both their own QoL and their partner’s QoL. Examining mutual effects between coping styles and QoL among survivors and their informal caregivers is an essential first step in providing comprehensive and cooperative care. The study has been reviewed by the Chinese Clinical Trial Registry, and registration information has been sent to the central database of the World Health Organization International Clinical Trial Registration Platform for global retrieval. This trial is registered with ChiCTR2300074087.
An Advanced Control Performance of a Sophisticated Stand-Alone Wind-Driven DFIG System
Authors: Youssef Omar E. M. , Hussien Mohamed G. , Hassan Abd El-Wahab
Published: August 2023

To supply resident loads far from the grid, a stand-alone wind system with a small-scale wind turbine and battery storage can be used. The traditional configuration of the system has a permanent-magnet synchronous generator (PMSG). Other alternative configurations use doubly fed induction generator (DFIG). The systems with DFIG have variable speed operation with a limited speed range which reduces the captured power from the wind turbine. Also, there is a rotor-side converter (RSC) which carries the reactive power of DFIG, in addition to the slip power. In this paper, an improved system configuration with DFIG is controlled by an advanced control scheme. By this advanced scheme, the speed range is increased such that maximum power operation of wind turbine is obtained for complete range of wind speed, and volt-ampere (VA) requirements of RSC are reduced by the operation at nearly zero-slip power.
Structural Damage Identification considering Uncertainties in Nonuniform Measurement Conditions Based on Convolution Neural Networks
Authors: Zhu Siyu , Xiang Tianyu
Published: August 2023

Dynamic-vibration-based structural damage identification (SDI) represents the main target for structural health monitoring (SHM). It is significant to consider the unavoidable uncertainties arising from both the structure and measuring noise. On the other hand, nonuniform measurement conditions often appear in actual SHM applications, which consist of two parts, i.e., spatial nonuniform characteristics for noises are induced by various intensities of input noise in every single sampling channel and multisensor stays in a damaged state. This paper proposes a new method for the SDI considering uncertainties in nonuniform measurement conditions integrating convolutional neural network (CNN). Herein, the great ability of feature extraction from the measurement associated with the convolutional network is used to handle the input data, and the mapping connection between the selected features and damage states is established. Time histories of structural responses, such as acceleration, are applied for damage identification. The application and accuracy of the CNN, which is trained with input uncertain parameters contaminated by stochastic noises, are verified by the finite element numerical and experimental results. Both uncertain parameters and measurement conditions are considered in the verification. The responses obtained from the numerical and experimental approach show that the proposed neural network model can identify the structural damage with high accuracy. The great robustness of the proposed method is examined by studying the influence of uncertainties, even considering the nonuniform measurement condition.
Data from Alpha-1 adrenergic antagonists sensitize neuroblastoma to therapeutic differentiation
Authors: Broso Francesca , Gatto Pamela , Sidarovich Viktoryia , Ambrosini Chiara , De Sanctis Veronica , Bertorelli Roberto , Zaccheroni Elena , Ricci Benedetta , Destefanis Eliana , Longhi Sara , Sebastiani Enrico , Tebaldi Toma , Adami Valentina , Quattrone Alessandro
Published: August 2023

Abstract
Neuroblastoma (NB) is an aggressive childhood tumor, with high-risk cases having a 5-year overall survival probability of approximately 50%. The multimodal therapeutic approach for NB includes treatment with the retinoid isotretinoin (13-cis retinoic acid; 13cRA), which is used in the post-consolidation phase as an anti-proliferation and pro-differentiation agent to minimize residual disease and prevent relapse. Through small molecule screening, we identified isorhamnetin (ISR) as a synergistic compound with 13cRA in inhibiting up to 80% of NB cell viability. The synergistic effect was accompanied by a marked increase in the expression of the adrenergic receptor α1B (ADRA1B) gene. Genetic knockout of ADRA1B or its specific blockade using ɑ1/ɑ1B adrenergic antagonists led to selective sensitization of MYCN-amplified NB cells to cell viability reduction and neural differentiation induced by 13cRA, thus mimicking ISR activity. Administration of doxazosin, a safe α1-antagonist used in pediatric patients, in combination with 13cRA in NB xenografted mice exerted marked control of tumor growth, while each drug alone was ineffective. Overall, this study identified the α1B adrenergic receptor as a pharmacological target in NB, supporting the evaluation of adding α1-antagonists to the post-consolidation therapy of NB to more efficiently control residual disease.
Data from Syk inhibition reprograms tumor-associated macrophages and overcomes gemcitabine-induced immunosuppression in pancreatic ductal adenocarcinoma
Authors: Rohila Deepak , Park In Hwan , Pham Timothy V. , Weitz Jonathan , Hurtado de Mendoza Tatiana , Madheswaran Suresh , Ishfaq Mehreen , Beaman Cooper , Tapia Elisabette , Sun Siming , Patel Jay , Tamayo Pablo , Lowy Andrew M. , Joshi Shweta
Published: August 2023

Abstract
Pancreatic ductal adenocarcinoma (PDAC) is an insidious disease with a low five-year survival rate. PDAC is characterized by infiltration of abundant tumor-associated macrophages (TAMs) that promote immune tolerance and immunotherapeutic resistance. Here we report that macrophage spleen tyrosine kinase (Syk) promotes PDAC growth and metastasis. In orthotopic PDAC mouse models, genetic deletion of myeloid Syk reprogrammed macrophages into immunostimulatory phenotype, increased the infiltration, proliferation, and cytotoxicity of CD8+ T cells, and repressed PDAC growth and metastasis. Furthermore, gemcitabine (Gem) treatment induced an immunosuppressive microenvironment in PDAC by promoting pro-tumorigenic polarization of macrophages. In contrast, treatment with the FDA-approved Syk inhibitor R788 (fostamatinib) remodeled the tumor immune microenvironment, “re-educated” pro-tumorigenic macrophages towards an immunostimulatory phenotype and boosted CD8+ T cell responses in Gem-treated PDAC in orthotopic mouse models and an ex vivo human pancreatic slice culture model. These findings illustrate the potential of Syk inhibition for enhancing the anti-tumor immune responses in PDAC and support the clinical evaluation of R788 either alone or together with Gem as a potential treatment strategy for PDAC.
Data from Syk Inhibition Reprograms Tumor-Associated Macrophages and Overcomes Gemcitabine-Induced Immunosuppression in Pancreatic Ductal Adenocarcinoma
Authors: Rohila Deepak , Park In Hwan , Pham Timothy V. , Weitz Jonathan , Hurtado de Mendoza Tatiana , Madheswaran Suresh , Ishfaq Mehreen , Beaman Cooper , Tapia Elisabette , Sun Siming , Patel Jay , Tamayo Pablo , Lowy Andrew M. , Joshi Shweta
Published: August 2023

Abstract
Pancreatic ductal adenocarcinoma (PDAC) is an insidious disease with a low 5-year survival rate. PDAC is characterized by infiltration of abundant tumor-associated macrophages (TAM), which promote immune tolerance and immunotherapeutic resistance. Here we report that macrophage spleen tyrosine kinase (Syk) promotes PDAC growth and metastasis. In orthotopic PDAC mouse models, genetic deletion of myeloid Syk reprogrammed macrophages into immunostimulatory phenotype, increased the infiltration, proliferation, and cytotoxicity of CD8+ T cells, and repressed PDAC growth and metastasis. Furthermore, gemcitabine (Gem) treatment induced an immunosuppressive microenvironment in PDAC by promoting protumorigenic polarization of macrophages. In contrast, treatment with the FDA-approved Syk inhibitor R788 (fostamatinib) remodeled the tumor immune microenvironment, “re-educated” protumorigenic macrophages towards an immunostimulatory phenotype and boosted CD8+ T-cell responses in Gem-treated PDAC in orthotopic mouse models and an ex vivo human pancreatic slice culture model. These findings illustrate the potential of Syk inhibition for enhancing the antitumor immune responses in PDAC and support the clinical evaluation of R788 either alone or together with Gem as a potential treatment strategy for PDAC.
Significance:
Syk blockade induces macrophage polarization to an immunostimulatory phenotype, which enhances CD8+ T-cell responses and improves gemcitabine efficacy in pancreatic ductal adenocarcinoma, a clinically challenging malignancy.
Supplementary Figure S2 from A Phase I, Multicenter, Open-Label, First-in-Human Study of DS-6157a in Patients with Advanced Gastrointestinal Stromal Tumor
Authors: George Suzanne , Heinrich Michael C. , Somaiah Neeta , Oppelt Peter , McLeod Robert , Nishioka Satoshi , Kundu Madan G. , Qian Xiaozhong , Kumar Prasanna , Laadem Abderrahmane , Lau Yvonne , Tran Brittany P. , Fallon Maura , Dosunmu Ololade , Shi Julia , Naito Yoichi
Published: August 2023

Supplementary Figure S2. DXd immunohistochemistry in a patient treated with 6.4 mg/kg DS-6157a (A) pre-treatment and (B) on treatment (Cycle 2, Day 10)
Supplementary Appendix 1 from A Phase I, Multicenter, Open-Label, First-in-Human Study of DS-6157a in Patients with Advanced Gastrointestinal Stromal Tumor
Authors: George Suzanne , Heinrich Michael C. , Somaiah Neeta , Oppelt Peter , McLeod Robert , Nishioka Satoshi , Kundu Madan G. , Qian Xiaozhong , Kumar Prasanna , Laadem Abderrahmane , Lau Yvonne , Tran Brittany P. , Fallon Maura , Dosunmu Ololade , Shi Julia , Naito Yoichi
Published: August 2023

Supplementary Appendix
Supplemental Figure 1 from Transcriptomic Signatures of MSI-High Metastatic Colorectal Cancer Predict Efficacy of Immune Checkpoint Inhibitors
Authors: Gallois Claire , Landi Matteo , Taieb Julien , Sroussi Marine , Saberzadeh-Ardestani Bahar , Cazelles Antoine , Lonardi Sara , Bergamo Francesca , Intini Rossana , Maddalena Giulia , Pietrantonio Filippo , Corti Francesca , Ambrosini Margherita , Martinetti Antonia , Germani Marco Maria , Boccaccio Chiara , Vetere Guglielmo , Mouillet-Richard Sophie , de Reynies Aurélien , Sinicrope Frank A. , Cremolini Chiara , Laurent-Puig Pierre
Published: August 2023

Selection of the transcriptomic signatures for the unsupervised clustering
Supplementary Spreadsheet S5 from Multiomic Mapping of Acquired Chromosome 1 Copy-Number and Structural Variants to Identify Therapeutic Vulnerabilities in Multiple Myeloma
Authors: Boyle Eileen M. , Blaney Patrick , Stoeckle James H. , Wang Yubao , Ghamlouch Hussein , Gagler Dylan , Braunstein Marc , Williams Louis , Tenenbaum Avital , Siegel Ariel , Chen Xiaoyi , Varma Gaurav , Avigan Jason , Li Alexander , Jinsi Monica , Kaminetzsky David , Arbini Arnaldo , Montes Lydia , Corre Jill , Rustad Even H. , Landgren Ola , Maura Francesco , Walker Brian A. , Bauer Michael , Bruno Benedetto , Tsirigos Aristotelis , Davies Faith E. , Morgan Gareth J.
Published: August 2023

Differential expression between normal chr1 and gain(1q) MM patients with t(4;14) translocation
Supplementary Spreadsheet S12 from Multiomic Mapping of Acquired Chromosome 1 Copy-Number and Structural Variants to Identify Therapeutic Vulnerabilities in Multiple Myeloma
Authors: Boyle Eileen M. , Blaney Patrick , Stoeckle James H. , Wang Yubao , Ghamlouch Hussein , Gagler Dylan , Braunstein Marc , Williams Louis , Tenenbaum Avital , Siegel Ariel , Chen Xiaoyi , Varma Gaurav , Avigan Jason , Li Alexander , Jinsi Monica , Kaminetzsky David , Arbini Arnaldo , Montes Lydia , Corre Jill , Rustad Even H. , Landgren Ola , Maura Francesco , Walker Brian A. , Bauer Michael , Bruno Benedetto , Tsirigos Aristotelis , Davies Faith E. , Morgan Gareth J.
Published: August 2023

Differentially hypomethylated and concurrently overexpressed genes in gain(1q) MM patients
Supplementary Table S1 from Identifying Mechanisms of Resistance by Circulating Tumor DNA in EVOLVE, a Phase II Trial of Cediranib Plus Olaparib for Ovarian Cancer at Time of PARP Inhibitor Progression
Authors: Lheureux Stephanie , Prokopec Stephenie D. , Oldfield Leslie E. , Gonzalez-Ochoa Eduardo , Bruce Jeffrey P. , Wong Derek , Danesh Arnavaz , Torti Dax , Torchia Jonathan , Fortuna Alexander , Singh Sharanjit , Irving Matthew , Marsh Kayla , Lam Bernard , Speers Vanessa , Yosifova Aleksandra , Oaknin Ana , Madariaga Ainhoa , Dhani Neesha C. , Bowering Valerie , Oza Amit M. , Pugh Trevor J.
Published: August 2023

Supplementary Table S1: Representativeness of Study Participants
Supplementary Figure S6 from Identifying Mechanisms of Resistance by Circulating Tumor DNA in EVOLVE, a Phase II Trial of Cediranib Plus Olaparib for Ovarian Cancer at Time of PARP Inhibitor Progression
Authors: Lheureux Stephanie , Prokopec Stephenie D. , Oldfield Leslie E. , Gonzalez-Ochoa Eduardo , Bruce Jeffrey P. , Wong Derek , Danesh Arnavaz , Torti Dax , Torchia Jonathan , Fortuna Alexander , Singh Sharanjit , Irving Matthew , Marsh Kayla , Lam Bernard , Speers Vanessa , Yosifova Aleksandra , Oaknin Ana , Madariaga Ainhoa , Dhani Neesha C. , Bowering Valerie , Oza Amit M. , Pugh Trevor J.
Published: August 2023

Supplementary Figure 6: Visualization of structural variants in cfDNA
Supplementary Figure S3 from Identifying Mechanisms of Resistance by Circulating Tumor DNA in EVOLVE, a Phase II Trial of Cediranib Plus Olaparib for Ovarian Cancer at Time of PARP Inhibitor Progression
Authors: Lheureux Stephanie , Prokopec Stephenie D. , Oldfield Leslie E. , Gonzalez-Ochoa Eduardo , Bruce Jeffrey P. , Wong Derek , Danesh Arnavaz , Torti Dax , Torchia Jonathan , Fortuna Alexander , Singh Sharanjit , Irving Matthew , Marsh Kayla , Lam Bernard , Speers Vanessa , Yosifova Aleksandra , Oaknin Ana , Madariaga Ainhoa , Dhani Neesha C. , Bowering Valerie , Oza Amit M. , Pugh Trevor J.
Published: August 2023

Supplementary Figure 3: Distribution of ctDNA levels and statistical association with clinical features
Supplementary Tables 1-8 from Development and Multicenter Case–Control Validation of Urinary Comprehensive Genomic Profiling for Urothelial Carcinoma Diagnosis, Surveillance, and Risk-Prediction
Authors: Salari Keyan , Sundi Debasish , Lee Jason J. , Wu Shulin , Wu Chin-Lee , DiFiore Gabrielle , Yan Q. Robert , Pienkny Andrew , Lee Chi K. , Oberlin Daniel , Barme Greg , Piser Joel , Kahn Robert , Collins Edward , Phillips Kevin G. , Caruso Vincent M. , Goudarzi Mahdi , Garcia-Ransom Monica , Lentz Peter S. , Evans-Holm Martha E. , MacBride Andrew R. , Fischer Daniel S. , Haddadzadeh Iden J. , Mazzarella Brian C. , Gray Joe W. , Koppie Theresa M. , Bicocca Vincent T. , Levin Trevor G. , Lotan Yair , Feldman Adam S.
Published: August 2023

Supplemental Tables 1-8
Supplementary Figure S3 from A Phase I/IIa Trial of Yttrium-90 Radioembolization in Combination with Durvalumab for Locally Advanced Unresectable Hepatocellular Carcinoma
Authors: Lee Yun Bin , Nam Joon Yeul , Cho Eun Ju , Lee Jeong-Hoon , Yu Su Jong , Kim Hyo-Cheol , Paeng Jin Chul , Yoon Jung-Hwan , Kim Yoon Jun
Published: August 2023

Supplementary Figure S3. Kaplan–Meier estimates of time to progression and overall survival according to BCLC stage in the per-protocol population. (A) Time to progression. (B) Overall survival. (C) Progression-free survival.
Supplementary Figure S1 from A Phase I/IIa Trial of Yttrium-90 Radioembolization in Combination with Durvalumab for Locally Advanced Unresectable Hepatocellular Carcinoma
Authors: Lee Yun Bin , Nam Joon Yeul , Cho Eun Ju , Lee Jeong-Hoon , Yu Su Jong , Kim Hyo-Cheol , Paeng Jin Chul , Yoon Jung-Hwan , Kim Yoon Jun
Published: August 2023

Supplementary Figure S1. Kaplan–Meier estimates of time to progression and overall survival in the per-protocol population. (A) Time to progression. (B) Overall survival. (C) Progression-free survival.
Suppl. Figure 3 from Endoglin, a Novel Biomarker and Therapeutical Target to Prevent Malignant Peripheral Nerve Sheath Tumor Growth and Metastasis
Authors: González-Muñoz Teresa , Di Giannatale Angela , García-Silva Susana , Santos Vanesa , Sánchez-Redondo Sara , Savini Claudia , Graña-Castro Osvaldo , Blanco-Aparicio Carmen , Fischer Suzanne , De Wever Olivier , Creus-Bachiller Edgar , Ortega-Bertran Sara , Pisapia David J. , Rodríguez-Peralto Jose L. , Fernández-Rodríguez Juana , Pérez-Portabella Cleofé Romagosa , Alaggio Rita , Benassi Maria Serena , Pazzaglia Laura , Scotlandi Katia , Ratner Nancy , Yohay Kaleb , Theuer Charles P. , Peinado Héctor
Published: August 2023

ENG knockdown does not affect MPNST cell apoptosis in vivo.
Supplementary Table S13 from Oncogenic Drivers and Therapeutic Vulnerabilities in KRAS Wild-Type Pancreatic Cancer
Authors: Singh Harshabad , Keller Rachel B. , Kapner Kevin S. , Dilly Julien , Raghavan Srivatsan , Yuan Chen , Cohen Elizabeth F. , Tolstorukov Michael , Andrews Elizabeth , Brais Lauren K. , da Silva Annacarolina , Perez Kimberly , Rubinson Douglas A. , Surana Rishi , Giannakis Marios , Ng Kimmie , Clancy Thomas E. , Yurgelun Matthew B. , Schlechter Benjamin L. , Clark Jeffrey W. , Shapiro Geoffrey I. , Rosenthal Michael H. , Hornick Jason L. , Nardi Valentina , Li Yvonne Y. , Gupta Hersh , Cherniack Andrew D. , Meyerson Matthew , Cleary James M. , Nowak Jonathan A. , Wolpin Brian M. , Aguirre Andrew J.
Published: August 2023

Pathway level comparison between KRAS WT Pancreatic cancers with and without MAPK alterations
Supplementary Table S12 from Oncogenic Drivers and Therapeutic Vulnerabilities in KRAS Wild-Type Pancreatic Cancer
Authors: Singh Harshabad , Keller Rachel B. , Kapner Kevin S. , Dilly Julien , Raghavan Srivatsan , Yuan Chen , Cohen Elizabeth F. , Tolstorukov Michael , Andrews Elizabeth , Brais Lauren K. , da Silva Annacarolina , Perez Kimberly , Rubinson Douglas A. , Surana Rishi , Giannakis Marios , Ng Kimmie , Clancy Thomas E. , Yurgelun Matthew B. , Schlechter Benjamin L. , Clark Jeffrey W. , Shapiro Geoffrey I. , Rosenthal Michael H. , Hornick Jason L. , Nardi Valentina , Li Yvonne Y. , Gupta Hersh , Cherniack Andrew D. , Meyerson Matthew , Cleary James M. , Nowak Jonathan A. , Wolpin Brian M. , Aguirre Andrew J.
Published: August 2023

Genomic comparison between KRAS WT Pancreatic cancers with and without MAPK alterations
Data from Transcriptomic Signatures of MSI-High Metastatic Colorectal Cancer Predict Efficacy of Immune Checkpoint Inhibitors
Authors: Gallois Claire , Landi Matteo , Taieb Julien , Sroussi Marine , Saberzadeh-Ardestani Bahar , Cazelles Antoine , Lonardi Sara , Bergamo Francesca , Intini Rossana , Maddalena Giulia , Pietrantonio Filippo , Corti Francesca , Ambrosini Margherita , Martinetti Antonia , Germani Marco Maria , Boccaccio Chiara , Vetere Guglielmo , Mouillet-Richard Sophie , de Reynies Aurélien , Sinicrope Frank A. , Cremolini Chiara , Laurent-Puig Pierre
Published: August 2023

AbstractPurpose:
Microsatellite instability (MSI) is currently the only predictive biomarker of efficacy of immune checkpoint inhibitors (ICI) in metastatic colorectal cancers (mCRC). However, 10% to 40% of patients with MSI mCRC will experience a primary resistance to ICI.
Experimental Design:
In two cohorts of patients with MSI mCRC treated with ICI (exploratory, N = 103; validation, N = 35), 3′ RNA sequencing was performed from primary tumors. Previously described single-cell transcriptomic signatures of tumor microenvironment (TME) were analyzed.
Results:
In the exploratory cohort, the unsupervised clustering allowed the identification of three clusters of tumors with distinct transcriptional profiles: cluster A (“stromalHIGH-proliferationLOW”), cluster B (“stromalHIGH-proliferationMED”), and cluster C (“stromalLOW-proliferationHIGH”), with an enrichment of patients progressing at first disease assessment under ICI in cluster A (30% vs. 12% in cluster B and 8.1% in cluster C; P = 0.074). Progression-free survival (PFS) was also significantly shorter in patients belonging to cluster A, compared with clusters B or C (P < 0.001) with 2-year PFS rates of 33.5%, 80.5%, and 78.3%, respectively. In multivariate analysis, PFS was still significantly longer in patients belonging to cluster B [HR, 0.19; 95% confidence interval (CI), 0.08–0.45; P < 0.001] and cluster C (HR, 0.25; 95% CI, 0.10–0.59; P = 0.02), compared with patients belonging to cluster A. The association of this clustering with PFS under ICI was confirmed in the validation cohort. PFS related to non–ICI-based regimens was not significantly different according to cluster.
Conclusions:
This unsupervised transcriptomic classification identified three groups of MSI mCRCs with different compositions of TME cells and proliferative capacities of TME/tumor cells. The “stromalHIGH-proliferationLOW” cluster is associated with a poorer prognosis with ICI treatment.
Data from A phase 1/2a trial of yttrium-90 radioembolization in combination with durvalumab for locally advanced unresectable hepatocellular carcinoma
Authors: Lee Yun Bin , Nam Joon Yeul , Cho Eun Ju , Lee Jeong-Hoon , Yu Su Jong , Kim Hyo-Cheol , Paeng Jin Chul , Yoon Jung-Hwan , Kim Yoon Jun
Published: August 2023

Abstract
Purpose: Synergistic effect of radiotherapy and immunotherapy for the treatment of hepatocellular carcinoma (HCC) has been reported. This phase 1/2a pilot trial evaluated preliminary efficacy and safety of combination of radioembolization with yttrium-90 microspheres (Y90-radioembolization) and durvalumab in patients with locally advanced unresectable HCC. Patients and Methods: Patients with Child-Pugh score ≤7 and locally advanced HCC, defined as Barcelona Clinic Liver Cancer (BCLC) stage B HCC or BCLC-C disease without extrahepatic metastases, received Y90-radioembolization followed by intravenous durvalumab 1500 mg 7–14 days after Y90-radioembolization and every 4 weeks thereafter. Primary endpoint was time to progression (TTP) assessed by modified RECIST (mRECIST). Secondary endpoints included overall survival (OS), progression-free survival (PFS), objective response rate (ORR) determined by mRECIST, and safety. Results: All 24 patients enrolled received Y90-radioembolization and 23 received at least one dose of durvalumab. Median follow-up duration was 19.0 months (range, 2.2–24.2). Median TTP was 15.2 months (95% confidence interval [CI], 6.1–not estimated). Median OS was not reached and 18-month OS rate was 58.3% (95% CI, 36.4–75.0). Median PFS was 6.9 months (95% CI, 5.4–15.2). Seven (29.2%) patients had a complete response and 13 (54.2%) had a partial response; ORR was 83.3% (95% CI, 62.6–95.3). Eleven (47.8%) patients experienced any-grade treatment-related adverse events. Two (8.7%) patients had grade 3 treatment-related adverse events (neutropenia and fever). None experienced any treatment-related serious adverse events. Conclusions: In patients with locally advanced unresectable HCC, the combination of Y90-radioembolization and durvalumab demonstrated promising efficacy and safety, warranting further evaluation in large-scale controlled trials.
Data from Endoglin, a novel biomarker and therapeutical target to prevent malignant peripheral nerve sheath tumor growth and metastasis
Authors: González-Muñoz Teresa , Di Giannatale Angela , Garcia-Silva Susana , Santos Vanesa , Sanchez-Redondo Sara , Savini Claudia , Graña-Castro Osvaldo , Blanco-Aparicio Carmen , Fischer Suzanne , De Wever Olivier , Creus-Bachiller Edgar , Ortega-Bertran Sara , Pisapia David J. , Rodríguez-Peralto José L. , Fernández-Rodríguez Juana , Romagosa Cleofe , Alaggio Rita , Benassi Maria Serena , Pazzaglia Laura , Scotlandi Katia , Ratner Nancy , Yohay Kaleb , Theuer Charles P. , Peinado Héctor
Published: August 2023

Abstract
Purpose: Malignant peripheral nerve sheath tumors (MPNSTs) are highly aggressive soft-tissue sarcomas that lack effective treatments, underscoring the urgent need to uncover novel mediators of MPNST pathogenesis that may serve as potential therapeutic targets. Tumor angiogenesis is considered a critical event in MPNST transformation and progression. Here, we have investigated whether endoglin (ENG), a TGF-β coreceptor with a crucial role in angiogenesis, could be a novel therapeutic target in MPNSTs. Experimental Design: ENG expression was evaluated in human peripheral nerve sheath tumor tissues and plasma samples. Effects of tumor cell-specific ENG expression on gene expression, signaling pathway activation and in vivo MPNST growth and metastasis were investigated. The efficacy of ENG targeting in monotherapy or in combination with MEK inhibition was analyzed in xenograft models. Results: ENG expression was found to be upregulated in both human MPNST tumor tissues and plasma circulating small extracellular vesicles. We demonstrated that ENG modulates Smad1/5 and MAPK/ERK pathway activation and pro-angiogenic and pro-metastatic gene expression in MPNST cells and plays an active role in tumor growth and metastasis in vivo. Targeting with ENG-neutralizing antibodies (TRC105/M1043) decreased MPNST growth and metastasis in xenograft models by reducing tumor cell proliferation and angiogenesis. Moreover, combination of anti-ENG therapy with MEK inhibition effectively reduced tumor cell growth and angiogenesis. Conclusions: Our data unveil a tumor-promoting function of ENG in MPNSTs and support the use of this protein as a novel biomarker and a promising therapeutic target for this disease.
MCR-21-0354_SF2 from Identification of a Novel FUS/ETV4 Fusion and Comparative Analysis with Other Ewing Sarcoma Fusion Proteins
Authors: Boone Megann A. , Taslim Cenny , Crow Jesse C. , Selich-Anderson Julia , Watson Mike , Heppner Peter , Hamill James , Wood Andrew C. , Lessnick Stephen L. , Winstanley Mark
Published: August 2023

Supp Figure 2 shows knockdown of endogenous EWS/FLI and expression of alternative FET/ETS fusions in the A673 Ewing sarcoma cell line.
TABLE 1B from Dual Blockade of EP2 and EP4 Signaling is Required for Optimal Immune Activation and Antitumor Activity Against Prostaglandin-Expressing Tumors
Authors: Francica Brian J. , Holtz Anja , Lopez Justine , Freund David , Chen Austin , Wang Dingzhi , Powell David , Kipper Franciele , Panigrahy Dipak , Dubois Raymond N. , Whiting Chan C. , Prasit Peppi , Dubensky Thomas W.
Published: August 2023

Antibodies used for IHC of APCmin/+ tumors
Chronisch entzündliche Darmerkrankungen – die Lunge im Blick behalten
Authors: Polke Markus
Published: August 2023

Background: No large, prospective study has investigated respiratory symptoms in patients with inflammatory bowel diseases. We aimed to describe the prevalence of and factors associated with respiratory symptoms in patients with inflammatory bowel disease. Methods: In an observational, prospective, cross-sectional study, we evaluated the frequency of respiratory symptoms using a validated self-reporting questionnaire from February 2019 to February 2021 during routine follow-up outpatient visits of patients with inflammatory bowel disease followed in the Gastroenterology Department of the Nancy University Hospital. In case of a positive questionnaire, patients were systematically offered a consultation with a pulmonologist in order to investigate a potential underlying respiratory disease. Results: There were 325 patients included, and 180 patients had a positive questionnaire (144 with Crohn’s disease). Of the included patients, 165 (50.8%) presented with respiratory symptoms, with dyspnea being the most frequent symptom (102 patients). There were 102 patients (56.7%) who benefited from a consultation in the pulmonology department: 43 (42.2%) were diagnosed with a respiratory disease, mainly asthma (n = 13) or chronic obstructive pulmonary disease (n = 10). Fourteen patients (13.7%) had obstructive sleep apnea. A body mass index increase, being a smoker or ex-smoker, and having articular extra-intestinal manifestations were independently associated with a higher prevalence of respiratory symptoms. Conclusions: Half of patients with inflammatory bowel disease reported respiratory symptoms in our study. Patients with inflammatory bowel disease should be systematically screened, as pulmonary disease is frequently present in this population, with specific attention being given to smokers or ex-smokers and patients with extra-articular intestinal manifestations.
Updated International Guidelines for Survivorship Care after Pediatric Cancer: Practice Implications in a German and Austrian Comprehensive Care Network
Authors: Gebauer Judith , Baust Katja , Bardi Edit , Grabow Desiree , Calminus Gabriele , Ronckers Cécile M , Langer Thorsten
Published: August 2023

Background: Timely diagnosis of treatment-related chronic health conditions in childhood cancer survivors (CCS) may result in reduced long-term morbidity and mortality. Evidence-based guidelines serve as a tool to implement risk-adapted screening examinations in long-term follow-up (LTFU) of CCS. Summary: New international LTFU guidelines from the last 3 years have been reviewed and included into a practical LTFU tool in order to provide an updated summary of LTFU recommendations. The inclusion of 13 new LTFU guidelines as well as 25 pragmatic recommendations resulted in an updated LTFU plan for implantation in daily practice. Special consideration of psychosocial and mental health aspects as well as recommendations for pregnant CCS complement holistic LTFU care. Key Messages: Risk-adapted LTFU in CCS offers the possibility for early detection and treatment of late effects. As these LTFU recommendations aim at asymptomatic individuals, benefits and potential risks of regular screening examinations have to be carefully balanced. Implementation of current evidence-based guidelines in clinical practice as well as the development of new application tools such as the Survivorship Passport can contribute to an individualized LTFU approach in order to ensure long-term health and quality of life in CCS.
Correlates of Food Addiction and Eating Behaviours in Patients with Morbid Obesity
Authors: Schankweiler Pia , Raddatz Dirk , Ellrott Thomas , Hauck Cirkel Carolin
Published: August 2023

Introduction: Food addiction (FA) is a promising construct regarding the multifactorial aetiology of obesity and the search for therapeutic approaches. However, there is an ongoing debate regarding the overlap/differentiation with eating disorders and the classification as a substance- or behaviour-related addiction. Energy-dense foods, especially those combining carbohydrates and fat, are associated with addictive eating and suspected of playing a role in the genesis of FA. This study aims to further understand the clinical significance of FA and to identify possible therapeutic targets. A special focus is set on potentially addictive foods (combination of carbohydrates and fat). Methods: Based on the Yale Food Addiction Scale 2.0, a cohort of 112 German adults with morbid obesity was divided into two sub-samples (patients with and without FA), which were examined for differences in the variables listed below. Results: The prevalence of FA was 25%. Patients meeting criteria for FA showed higher degrees of hunger, emotional, binge, and night eating than patients without FA. In addition, hunger and disinhibition were found to be significant predictors of FA. FA was not associated with sex, age, body mass index (BMI), cognitive restraint, rigid and flexible control, prevalence of substance use, age of onset of obesity, stress level, level of social support, reduction of BMI during a weight loss programme, or programme withdrawal rate. There was no significant difference in the consumption of foods rich in both carbohydrates and fat, nor of fat or carbohydrates alone. Conclusion: FA can be considered as a sub-phenotype of obesity, occurring in approximately 25% of obesity cases. Dysfunctional emotional coping mechanisms associated with low distress tolerance showed to be significantly related to FA and should be targeted therapeutically. Behavioural interventions should include a bio-psycho-social model. Binge eating episodes were found to be characteristic for FA and the already stated overlap between FA and binge eating behaviour can be confirmed. The results do not support a decisive difference due to a substance-related component of FA. Despite this, the existence of FA as a distinct entity cannot be excluded, as not all patients with FA exhibit binges.
Cognitive Impairment and Risk Factors in Post-COVID-19 Hospitalized Patients
Authors: Khieukhajee Jedsada , Rojana-udomsart Arada , Srisarakorn Pinnakarn , Wongsurit Tanaphon , Aungsumart Saharat
Published: August 2023

Introduction: Numerous reports regarding cognitive deficits after the coronavirus disease 2019 (COVID-19), described as “brain fog,” have been published. However, the clinical presentations and risk factors of post-COVID-19 cognitive impairment are controversial. This study aimed to assess (a) the prevalence of cognitive impairment after COVID-19 hospitalization, (b) characteristics of the cognitive deficits, (c) risk factors of post-COVID-19 cognitive impairment, and (d) comparison of cognitive function between post-COVID-19 patients and healthy people. Methods: The study comprised 34 SARS-CoV-2-infected patients, admitted to the Neurological Institute of Thailand during the peak of COVID-19 pandemic in 2021–2022. These patients came for neuropsychological and clinical evaluations at 2-week follow-up visit. The cognitive impairment and characteristics were measured by TMSE and MoCA. Clinical risk factors and post-COVID-19 cognitive impairment were assessed. The comparison of cognitive function in post-acute COVID-19 patients and 22 healthy controls was also performed. Results: The prevalence of post-COVID-19 cognitive impairment defined by a total MoCA score below 25 points was 61.76%. Years of education were the only predictive factors related to cognitive impairment. Our multivariate analysis revealed no statistical difference in cognitive outcomes between post-acute COVID-19 patients and healthy controls. Conclusion: This study showed a moderate prevalence of cognitive dysfunction after COVID-19 hospitalization similar to previous reports. However, there was no significant difference in cognitive measurements between these patients and healthy people. Whether SARS-CoV-2 infection causes cognitive dysfunction is a myth or fact that still has a long way to prove via further longitudinal study.