bluuebunny/crossref_metadata_2025 huggingface dataset:
Lung cancer survivors’ views on telerehabilitation following curative intent therapy: a formative qualitative study
Authors: Ha Duc M , Nunnery Mary A , Klocko Robert P , Haverhals Leah M , Bekelman David B , New Melissa L , Randhawa Simran K , Stevens-Lapsley Jennifer E , Studts Jamie L , Prochazka Allan V , Keith Robert L
Published: June 2023

Objectives

To inform personalised home-based rehabilitation interventions, we sought to gain in-depth understanding of lung cancer survivors’ (1) attitudes and perceived self-efficacy towards telemedicine; (2) knowledge of the benefits of rehabilitation and exercise training; (3) perceived facilitators and preferences for telerehabilitation; and (4) health goals following curative intent therapy.

Design

We conducted semi-structured interviews guided by Bandura’s Social Cognitive Theory and used directed content analysis to identify salient themes.

Setting

One USA Veterans Affairs Medical Center.

Participants

We enrolled 20 stage I–IIIA lung cancer survivors who completed curative intent therapy in the prior 1–6 months. Eighty-five percent of participants had prior experience with telemedicine, but none with telerehabilitation or rehabilitation for lung cancer.

Results

Participants viewed telemedicine as convenient, however impersonal and technologically challenging, with most reporting low self-efficacy in their ability to use technology. Most reported little to no knowledge of the potential benefits of specific exercise training regimens, including those directed towards reducing dyspnoea, fatigue or falls. If they were to design their own telerehabilitation programme, participants had a predominant preference for live and one-on-one interaction with a therapist, to enhance therapeutic relationship and ensure correct learning of the training techniques. Most participants had trouble stating their explicit health goals, with many having questions or concerns about their lung cancer status. Some wanted better control of symptoms and functional challenges or engage in healthful behaviours.

Conclusions

Features of telerehabilitation interventions for lung cancer survivors following curative intent therapy may need to include strategies to improve self-efficacy and skills with telemedicine. Education to improve knowledge of the benefits of rehabilitation and exercise training, with alignment to patient-formulated goals, may increase uptake. Exercise training with live and one-on-one therapist interaction may enhance learning, adherence, and completion. Future work should determine how to incorporate these features into telerehabilitation.
Critical Care Cycling to ImproveLowerExtremity Strength (CYCLE): protocol for an international, multicentre randomised clinical trial of early in-bed cycling for mechanically ventilated patients
Authors: Kho Michelle E , Reid Julie , Molloy Alexander J , Herridge Margaret S , Seely Andrew J , Rudkowski Jill C , Buckingham Lisa , Heels-Ansdell Diane , Karachi Tim , Fox-Robichaud Alison , Ball Ian M , Burns Karen E A , Pellizzari Joseph R , Farley Christopher , Berney Sue , Pastva Amy M , Rochwerg Bram , D'Aragon Frédérick , Lamontagne Francois , Duan Erick H , Tsang Jennifer L Y , Archambault Patrick , English Shane W , Muscedere John , Serri Karim , Tarride Jean-Eric , Mehta Sangeeta , Verceles Avelino C , Reeve Brenda , O'Grady Heather , Kelly Laurel , Strong Geoff , Hurd Abby H , Thabane Lehana , Cook Deborah J
Published: June 2023

Introduction

In-bed leg cycling with critically ill patients is a promising intervention aimed at minimising immobility, thus improving physical function following intensive care unit (ICU) discharge. We previously completed a pilot randomised controlled trial (RCT) which supported the feasibility of a large RCT. In this report, we describe the protocol for an international, multicentre RCT to determine the effectiveness of early in-bed cycling versus routine physiotherapy (PT) in critically ill, mechanically ventilated adults.

Methods and analysis

We report a parallel group RCT of 360 patients in 17 medical-surgical ICUs and three countries. We include adults (≥18 years old), who could ambulate independently before their critical illness (with or without a gait aid), ≤4 days of invasive mechanical ventilation and ≤7 days ICU length of stay, and an expected additional 2-day ICU stay, and who do not fulfil any of the exclusion criteria. After obtaining informed consent, patients are randomised using a web-based, centralised system to either 30 min of in-bed cycling in addition to routine PT, 5 days per week, up to 28 days maximum, or routine PT alone. The primary outcome is the Physical Function ICU Test-scored (PFIT-s) at 3 days post-ICU discharge measured by assessors blinded to treatment allocation. Participants, ICU clinicians and research coordinators are not blinded to group assignment. Our sample size estimate was based on the identification of a 1-point mean difference in PFIT-s between groups.

Ethics and dissemination

Critical Care Cycling to improveLowerExtremity (CYCLE) is approved by the Research Ethics Boards of all participating centres and Clinical Trials Ontario (Project 1345). We will disseminate trial results through publications and conference presentations.

Trial registration number

NCT03471247(Full RCT);NCT02377830(CYCLE Vanguard 46 patient internal pilot).
Viz LVO versus Rapid LVO in detection of large vessel occlusion on CT angiography for acute stroke
Authors: Delora Adam , Hadjialiakbari Christopher , Percenti Eryn , Torres Jordan , Alderazi Yazan J , Ezzeldin Rime , Hassan Ameer E , Ezzeldin Mohamad
Published: June 2023

Background

Endovascular thrombectomy improves outcomes and reduces mortality for large vessel occlusion (LVO) and is time-sensitive. Computer automation may aid in the early detection of LVOs, but false values may lead to alarm desensitization. We compared Viz LVO and Rapid LVO for automated LVO detection.

Methods

Data were retrospectively extracted from Rapid LVO and Viz LVO running concurrently from January 2022 to January 2023 on CT angiography (CTA) images compared with a radiologist interpretation. We calculated diagnostic accuracy measures and performed a McNemar test to look for a difference between the algorithms’ errors. We collected demographic data, comorbidities, ejection fraction (EF), and imaging features and performed a multiple logistic regression to determine if any of these variables predicted the incorrect classification of LVO on CTA.

Results

360 participants were included, with 47 large vessel occlusions. Viz LVO and Rapid LVO had a specificity of 0.96 and 0.85, a sensitivity of 0.87 and 0.87, a positive predictive value of 0.75 and 0.46, and a negative predictive value of 0.98 and 0.97, respectively. A McNemar test on correct and incorrect classifications showed a statistically significant difference between the two algorithms’ errors (P=0.00000031). A multiple logistic regression showed that low EF (Viz P=0.00125, Rapid P=0.0286) and Modified Woodcock Score >1 (Viz P=0.000198, Rapid P=0.000000975) were significant predictors of incorrect classification.

Conclusion

Rapid LVO produced a significantly larger number of false positive values that may contribute to alarm desensitization, leading to missed alarms or delayed responses. EF and intracranial atherosclerosis were significant predictors of incorrect predictions.
Atrial fibrillation is associated with higher first pass effect following thrombectomy for large vessel occlusion
Authors: Pillai Presaad , Bush Steven J , Kusuma Yohanna , Churilov Leonid , Dowling Richard J , Luu Vu Dang , Davis Stephen M , Mitchell Peter J , Yan Bernard
Published: June 2023

Background

First pass effect (FPE), defined as single-pass complete or near complete reperfusion during endovascular thrombectomy (EVT) for large vessel occlusion (LVO) strokes, is a critical performance metric. Atrial fibrillation (AF)-related strokes have different clot composition compared with non-AF strokes, which may impact thrombectomy reperfusion results. We compared FPE rates in AF and non-AF stroke patients to evaluate if AF-related strokes had higher FPE rates.

Methods

We conducted a post-hoc analysis of the DIRECT-SAFE trial data, including patients with retrievable clots on the initial angiographic run. Patients were categorized into AF and non-AF groups. The primary outcome was the presence or absence of FPE (single-pass, single-device resulting in complete/near complete reperfusion) in AF and non-AF groups. We used multivariable logistic regression to examine the association between FPE and AF, adjusting for thrombolysis pre-thrombectomy and clot location.

Results

We included 253 patients (67 with AF, 186 without AF). AF patients were older (mean age: 74 years vs 67.5 years, p=0.001), had a higher proportion of females (55% vs 40%, p=0.044), and experienced more severe strokes (median National Institutes of Health Stroke Scale (NIHSS) score: 17 vs 14, p=0.009) than non-AF patients. No differences were observed in thrombolytic agent usage, time metrics, or clot location. AF patients achieved a higher proportion of FPE compared with non-AF patients (55.22% vs 37.3%, adjusted odds ratio 2.00 (95% CI 1.13 to 3.55), p=0.017).

Conclusions

AF-related strokes in LVO patients treated with EVT were associated with FPE. This highlights the need for preparedness for multiple passes and potential adjuvant/rescue therapy in non-AF-related strokes.
High variability in physician estimations of flow-diverting stent deployment versus PreSize Neurovascular software simulation: a comparison study
Authors: Rai Ansaar T , Boo SoHyun , Downer Jonathan , DuPlessis Johannes , Rautio Riitta , Sinisalo Matias , Pekkola Johanna , Carraro do Nascimento Vinicius , Given Curtis , Patankar Tufail
Published: June 2023

Background

Physician variablity in preoperative planning of endovascular implant deployment and associated inaccuracies have not been documented. This study aimed to quantify the variability in accuracy of physician flow diverter (FD) planning and directly compares it with PreSize Neurovascular (Oxford Heartbeat Ltd) software simulations.

Methods

Eight experienced neurointerventionalists (NIs), blinded to procedural details, were provided with preoperative 3D rotational angiography (3D-RA) volumetric data along with images annotated with the distal landing location of a deployed Surpass Evolve (Stryker Neurovascular) FD from 51 patient cases. NIs were asked to perform a planning routine reflecting their normal practice and estimate the stent’s proximal landing using volumetric data and the labeled dimensions of the FD used. Equivalent deployed length estimation was performed using PreSize software. NI- and software-estimated lengths were compared with postprocedural observed deployed stent length (control) using Bland–Altman plots. NI assessment agreement was assessed with the intraclass correlation coefficient (ICC).

Results

The mean accuracy of NI-estimated deployed FD length was 81% (±15%) versus PreSize’s accuracy of 95% (±4%), demonstrating significantly higher accuracy for the software (p<0.001). The mean absolute error between estimated and control lengths was 4 mm (±3.5 mm, range 0.03–30.2 mm) for NIs and 1 mm (±0.9 mm, range 0.01–3.9 mm) for PreSize. No discernable trends in accuracy among NIs or across vasculature and aneurysm morphology (size, vessel diameter, tortuousity) were found.

Conclusions

The study quantified experienced physicians’ significant variablity in predicting an FD deployment with current planning approaches. In comparison, PreSize-simulated FD deployment was consistently more accurate and reliable, demonstrating its potential to improve standard of practice.
Carotid artery direct access for intracranial stenting of a stroke patient with an aberrant left common carotid artery and right aorta
Authors: Fu Weilun , Liu Xinke , Yang Bo , Yan Zhaoyang , Jia Baixue , He Ying , Ma Ning
Published: June 2023

A right aortic arch is present in 0.1% of the population and can occur in isolation or be associated with congenital heart disease.1 Moreover, the most common form of right aortic arch in adults is associated with an aberrant left subclavian artery.1 An aberrant left common carotid artery that originated from the ascending aorta with the right aorta is very rare. In this situation, carotid direct access was considered to avoid access challenge due to a large curve from the ascending aorta to the left common carotid artery.2 3 Here we demonstrate carotid artery direct access for intracranial stenting of a stroke patient with aberrant left common carotid artery and right aorta. Manual compression with a long time under general anesthesia to avoid post-procedural puncture site hematoma is recommended (video 1).

Video 1

 Carotid artery direct access
Good death from cancer–the patient view: systematic review of qualitative studies
Authors: Wang Guiyun , Xiao Jinnan , Chen Zhihan , Huang Chongmei , Deng Yinghua , Tang Siyuan
Published: June 2023

Background and objective

An in-depth understanding of what constitutes a good death among patients with cancer is vital to providing patient-centred palliative care. This review aimed to synthesise evidence on the perceptions of a good death among patients with cancer.

Methods

This systematic review involved a synthesis of qualitative data. A three-step process suggested by the Joanna Briggs Institute was used to synthesise the data.

Results

A total of 1432 records were identified, and five articles met the inclusion criteria. Seven synthesised findings emerged: (1) being aware of cancer, (2) pain and symptom management, (3) dying well, (4) being remembered after death, (5) individual perspectives of a good death, (6) individual behaviours leading to a good death, and (7) culture and religions. A structural framework was developed to elicit two layers that could be regarded as determinants of a good death. One layer suggested how multiple external issues impact a good death, whereas the other layer involves patients’ internal attributes that shape their experiences of a good death. The elements in the two layers were inter-related to exert a crossover effect on good death in specific cultural and religious contexts.

Conclusion

A good death is a process initiated from the time of awareness of cancer and extends beyond demise. Holistic approaches encompassing the management of physical and psychological distress along with psychosocial behavioural interventions to enhance patients’ positive perspectives and behaviours are recommended to improve their quality of life and death.
FlowerCast: Efficient Time-sensitive Multicast in Wireless Sensor Networks with Link Uncertainty
Authors: Tang Jianzhi , Fu Luoyi , Liang Shiyu , Long Fei , Zhou Lei , Wang Xinbing , Zhou Chenghu
Published: June 2023

This article studies time-sensitive multicast in wireless sensor networks (WSNs) with link uncertainty, where information from the source needs to be delivered to multiple receivers within an imposed delay constraint. Prior art on static WSNs minimizes the multicast delay via the construction of a multicast tree that approximates the Steiner tree in length, which, however, may be invalidated by the time-varying network topology of WSNs with uncertain link states. Moreover, for multicast in WSNs with link uncertainty, the possible link failure necessitates a suitable measurement of the uncertain communication distance and calls for the performance guarantee in both delay and delivery ratio. In this work, by modeling a WSN as a random graph with each link associated with a transmission probability, we propose FlowerCast, an efficient multicast scheme, to jointly minimize the expected multicast delay and to maximize the expected delivery ratio of multicast under delay constraint. The core of FlowerCast is to quantify the uncertain communication distance by the expected transmission delay of a time-varying path, based on which a delay-optimal multicast tree is constructed in accordance with the directionality of delay. Candidate paths with a high expected delivery ratio and low expected delay are then selected in a distributed manner to conditionally connect adjacent multicast members and thus transform the multicast tree into a multicast flower. Despite the NP-hardness of optimal candidate paths’ addition, the transformation with the highest expected delivery ratio of multicast under delay constraint can be guaranteed through a pseudo-polynomial time derandomization-based greedy approach. We further demonstrate the time and energy efficiency of FlowerCast through asymptotic analysis. To make full use of the possible overlapping links in a multicast flower, a hybrid routing strategy is presented to wisely switch between sequential routing and synchronous routing for extra enhancement of the multicast performance. Extensive experiments on various datasets verify the superiority of FlowerCast and hybrid routing over baselines and indicate their wide applicability to practical scenarios.
Synergetic Development Measure of Airport Groups Composite System and Its Influencing Factors Analysis: Some Evidence from China
Authors: Zhang Peiwen , Ding Rui , Wang Yu , Zhang Qiaoyan
Published: June 2023

Whether airport groups develop synergistically has become a concern for the aviation industry. Existing studies have neglected the dynamic comprehensive evaluation and analysis of influencing factors of synergy degree. Taking the synergistic development of airport groups as the research perspective, we integrate the dynamic comprehensive evaluation model into the traditional synergy model. From two dimensions of airport development and regional economy, we measured the static synergy degree of the Chengdu-Chongqing airport group and the dynamic synergetic development degree on the overall time series. Further, using a spatial econometric model, we construct a distance economy-nested spatial weight matrix so as to explore the influence of each indicator on the synergy degree of the composite system. The results show that the overall synergy of the Chengdu-Chongqing airport group is above 0.5 in terms of static synergy degree. The clustering spectrum shows that the Chengdu-Chongqing airport group can be divided into three categories and basically forms the characteristic of “two main and multiple auxiliary airports.” In terms of dynamic synergetic development degree and comprehensive evaluation value, the change speed of synergy degree is relatively smooth in the early stage and fluctuates in the later stage, and the overall dynamic evaluation value of the Chongqing regional airports is high. The effects of the explanatory variables of the airport group composite system on the synergy degree show more direct effects than spillover effects, and the direct effects are all positive feedback effects, while the negative spillover effects of the explanatory variables cannot be ignored.
Table S5 from Caffeine Supplementation and FOXM1 Inhibition Enhance the Antitumor Effect of Statins in Neuroblastoma
Authors: Tran Gia-Buu , Ding Jane , Ye Bingwei , Liu Mengling , Yu Yajie , Zha Yunhong , Dong Zheng , Liu Kebin , Sudarshan Sunil , Ding Han-Fei
Published: June 2023

Go analysis of genes up-regulated by simvastatin
Table S3 from MEN1 Degradation Induced by Neddylation and the CUL4B–DCAF7 Axis Promotes Pancreatic Neuroendocrine Tumor Progression
Authors: Xu Junfeng , Ye Zeng , Zhuo Qifeng , Gao Heli , Qin Yi , Lou Xin , Zhang Wuhu , Wang Fei , Wang Yan , Jing Desheng , Fan Guixiong , Zhang Yue , Chen Xuemin , Chen Jie , Xu Xiaowu , Yu Xianjun , Ji Shunrong
Published: June 2023

Gene mutation analysis identified in 50 patients with PanNETs
Supplementary Data from β-Catenin–Driven Differentiation Is a Tissue-Specific Epigenetic Vulnerability in Adrenal Cancer
Authors: Mohan Dipika R. , Borges Kleiton S. , Finco Isabella , LaPensee Christopher R. , Rege Juilee , Solon April L. , Little Donald W. , Else Tobias , Almeida Madson Q. , Dang Derek , Haggerty-Skeans James , Apfelbaum April A. , Vinco Michelle , Wakamatsu Alda , Mariani Beatriz M.P. , Amorim Larissa Costa , Latronico Ana Claudia , Mendonca Berenice B. , Zerbini Maria Claudia N. , Lawlor Elizabeth R. , Ohi Ryoma , Auchus Richard J. , Rainey William E. , Marie Suely K.N. , Giordano Thomas J. , Venneti Sriram , Fragoso Maria Candida Barisson Villares , Breault David T. , Lerario Antonio Marcondes , Hammer Gary D.
Published: June 2023

Supplementary Table 1: NCI-H295R RNA-seq FPKM table, Related to Figures 2-4, 6.
Figure S2 from MEN1 Degradation Induced by Neddylation and the CUL4B–DCAF7 Axis Promotes Pancreatic Neuroendocrine Tumor Progression
Authors: Xu Junfeng , Ye Zeng , Zhuo Qifeng , Gao Heli , Qin Yi , Lou Xin , Zhang Wuhu , Wang Fei , Wang Yan , Jing Desheng , Fan Guixiong , Zhang Yue , Chen Xuemin , Chen Jie , Xu Xiaowu , Yu Xianjun , Ji Shunrong
Published: June 2023

Representative tandem MS spectrum of the QATGIEDGELR peptide from CUL4B as determined by IP-Mass Spec
Supplementary Data from Attenuation of Sialylation Augments Antitumor Immunity and Improves Response to Immunotherapy in Ovarian Cancer
Authors: Cao Kankan , Zhang Guodong , Yang Moran , Wang Yiying , He Mengdi , Zhang Chen , Huang Yan , Lu Jiaqi , Liu Haiou
Published: June 2023

Materials and Methods༛Supplementary Figure S1 to S14 for multiple supplementary figures
Supplementary Table 9_Pro metastatic pathways identified by differential expression singlePT setting from A Rare Subset of Primary Tumor Cells with Concomitant Hyperactivation of Extracellular Matrix Remodeling and dsRNA-IFN1 Signaling Metastasizes in Breast Cancer
Authors: Roda Niccolò , Cossa Andrea , Hillje Roman , Tirelli Andrea , Ruscitto Federica , Cheloni Stefano , Priami Chiara , Dalmasso Alberto , Gambino Valentina , Blandano Giada , Polazzi Andrea , Falvo Paolo , Gatti Elena , Mazzarella Luca , Luzi Lucilla , Migliaccio Enrica , Pelicci Pier Giuseppe
Published: June 2023

Supplementary Table reporting the Pro metastatic pathways identified by differential expression in singlePT setting
Supplementary Table 8_Genes identified by classification analysis in pro vs non metastatic clones from A Rare Subset of Primary Tumor Cells with Concomitant Hyperactivation of Extracellular Matrix Remodeling and dsRNA-IFN1 Signaling Metastasizes in Breast Cancer
Authors: Roda Niccolò , Cossa Andrea , Hillje Roman , Tirelli Andrea , Ruscitto Federica , Cheloni Stefano , Priami Chiara , Dalmasso Alberto , Gambino Valentina , Blandano Giada , Polazzi Andrea , Falvo Paolo , Gatti Elena , Mazzarella Luca , Luzi Lucilla , Migliaccio Enrica , Pelicci Pier Giuseppe
Published: June 2023

Supplementary Table reporting the genes identified by classification analysis in pro vs non metastatic clones
Supplementary Data from Periostin+ Stromal Cells Guide Lymphovascular Invasion by Cancer Cells
Authors: Null Jamie L. , Kim Dae Joong , McCann James V. , Pramoonjago Patcharin , Fox Jay W. , Zeng Jianhao , Kumar Pankaj , Edatt Lincy , Pecot Chad V. , Dudley Andrew C.
Published: June 2023

Data supplement
Supplementary Table 6_Gene modules analysis_GO and curated pathways associated to gene modules from A Rare Subset of Primary Tumor Cells with Concomitant Hyperactivation of Extracellular Matrix Remodeling and dsRNA-IFN1 Signaling Metastasizes in Breast Cancer
Authors: Roda Niccolò , Cossa Andrea , Hillje Roman , Tirelli Andrea , Ruscitto Federica , Cheloni Stefano , Priami Chiara , Dalmasso Alberto , Gambino Valentina , Blandano Giada , Polazzi Andrea , Falvo Paolo , Gatti Elena , Mazzarella Luca , Luzi Lucilla , Migliaccio Enrica , Pelicci Pier Giuseppe
Published: June 2023

Supplementary Table including Gene modules analysis and GO and curated pathways associated to gene modules
Supplementary Table 2_Predictive power of genes and signatures_Patient cohorts GEO accession number from A Rare Subset of Primary Tumor Cells with Concomitant Hyperactivation of Extracellular Matrix Remodeling and dsRNA-IFN1 Signaling Metastasizes in Breast Cancer
Authors: Roda Niccolò , Cossa Andrea , Hillje Roman , Tirelli Andrea , Ruscitto Federica , Cheloni Stefano , Priami Chiara , Dalmasso Alberto , Gambino Valentina , Blandano Giada , Polazzi Andrea , Falvo Paolo , Gatti Elena , Mazzarella Luca , Luzi Lucilla , Migliaccio Enrica , Pelicci Pier Giuseppe
Published: June 2023

Supplementary Table including information about the predictive power of genes and signatures identified from metastatic clones and patient cohorts GEO accession numbers
Supplementary Table 1_Primer and shRNA sequences_PCR cycles_Mycoplasma testing from A Rare Subset of Primary Tumor Cells with Concomitant Hyperactivation of Extracellular Matrix Remodeling and dsRNA-IFN1 Signaling Metastasizes in Breast Cancer
Authors: Roda Niccolò , Cossa Andrea , Hillje Roman , Tirelli Andrea , Ruscitto Federica , Cheloni Stefano , Priami Chiara , Dalmasso Alberto , Gambino Valentina , Blandano Giada , Polazzi Andrea , Falvo Paolo , Gatti Elena , Mazzarella Luca , Luzi Lucilla , Migliaccio Enrica , Pelicci Pier Giuseppe
Published: June 2023

Supplementary table including information about Primer and shRNA sequences, PCR cycles, and Mycoplasma testing strategy
Supplementary Materials and Methods from A Rare Subset of Primary Tumor Cells with Concomitant Hyperactivation of Extracellular Matrix Remodeling and dsRNA-IFN1 Signaling Metastasizes in Breast Cancer
Authors: Roda Niccolò , Cossa Andrea , Hillje Roman , Tirelli Andrea , Ruscitto Federica , Cheloni Stefano , Priami Chiara , Dalmasso Alberto , Gambino Valentina , Blandano Giada , Polazzi Andrea , Falvo Paolo , Gatti Elena , Mazzarella Luca , Luzi Lucilla , Migliaccio Enrica , Pelicci Pier Giuseppe
Published: June 2023

Supplementary Materials and Methods, including a deeper characterisation of the Methods outlined in the Main manuscript and the description of additional analyses not included in the main text
Supplementary Figures and legends from A Rare Subset of Primary Tumor Cells with Concomitant Hyperactivation of Extracellular Matrix Remodeling and dsRNA-IFN1 Signaling Metastasizes in Breast Cancer
Authors: Roda Niccolò , Cossa Andrea , Hillje Roman , Tirelli Andrea , Ruscitto Federica , Cheloni Stefano , Priami Chiara , Dalmasso Alberto , Gambino Valentina , Blandano Giada , Polazzi Andrea , Falvo Paolo , Gatti Elena , Mazzarella Luca , Luzi Lucilla , Migliaccio Enrica , Pelicci Pier Giuseppe
Published: June 2023

Supplementary Figures 1 to 6 and corresponding legends
Data from Metabolic Reprogramming Driven by IGF2BP3 Promotes Acquired Resistance to EGFR Inhibitors in Non–Small Cell Lung Cancer
Authors: Lin Ziyou , Li Jingwei , Zhang Jian , Feng Weineng , Lu Jiaye , Ma Xiaofan , Ding Wen , Ouyang Shumin , Lu Jinjian , Yue Peibin , Wan Guohui , Liu Peiqing , Zhang Xiaolei
Published: June 2023

Abstract
Acquired resistance represents a bottleneck for effective molecular targeted therapy in lung cancer. Metabolic adaptation is a distinct hallmark of human lung cancer that might contribute to acquired resistance. In this study, we discovered a novel mechanism of acquired resistance to EGFR tyrosine kinase inhibitors (TKI) mediated by IGF2BP3-dependent cross-talk between epigenetic modifications and metabolic reprogramming through the IGF2BP3–COX6B2 axis. IGF2BP3 was upregulated in patients with TKI-resistant non–small cell lung cancer, and high IGF2BP3 expression correlated with reduced overall survival. Upregulated expression of the RNA binding protein IGF2BP3 in lung cancer cells reduced sensitivity to TKI treatment and exacerbated the development of drug resistance via promoting oxidative phosphorylation (OXPHOS). COX6B2 mRNA bound IGF2BP3, and COX6B2 was required for increased OXPHOS and acquired EGFR-TKI resistance mediated by IGF2BP3. Mechanistically, IGF2BP3 bound to the 3′-untranslated region of COX6B2 in an m6A-dependent manner to increase COX6B2 mRNA stability. Moreover, the IGF2BP3–COX6B2 axis regulated nicotinamide metabolism, which can alter OXPHOS and promote EGFR-TKI acquired resistance. Inhibition of OXPHOS with IACS-010759, a small-molecule inhibitor, resulted in strong growth suppression in vitro and in vivo in a gefitinib-resistant patient-derived xenograft model. Collectively, these findings suggest that metabolic reprogramming by the IGF2BP3–COX6B2 axis plays a critical role in TKI resistance and confers a targetable metabolic vulnerability to overcome acquired resistance to EGFR-TKIs in lung cancer.
Significance:
IGF2BP3 stabilizes COX6B2 to increase oxidative phosphorylation and to drive resistance to EGFR inhibitors in lung cancer, which provides a therapeutic strategy to overcome acquired resistance by targeting metabolic transitions.
Data from Periostin+ Stromal Cells Guide Lymphovascular Invasion by Cancer Cells
Authors: Null Jamie L. , Kim Dae Joong , McCann James V. , Pramoonjago Patcharin , Fox Jay W. , Zeng Jianhao , Kumar Pankaj , Edatt Lincy , Pecot Chad V. , Dudley Andrew C.
Published: June 2023

Abstract
Cancer cell dissemination to sentinel lymph nodes is associated with poor patient outcomes, particularly in breast cancer. The process by which cancer cells egress from the primary tumor upon interfacing with the lymphatic vasculature is complex and driven by dynamic interactions between cancer cells and stromal cells, including cancer-associated fibroblasts (CAF). The matricellular protein periostin can distinguish CAF subtypes in breast cancer and is associated with increased desmoplasia and disease recurrence in patients. However, as periostin is secreted, periostin-expressing CAFs are difficult to characterize in situ, limiting our understanding of their specific contribution to cancer progression. Here, we used in vivo genetic labeling and ablation to lineage trace periostin+ cells and characterize their functions during tumor growth and metastasis. Periostin-expressing CAFs were spatially found at periductal and perivascular margins, were enriched at lymphatic vessel peripheries, and were differentially activated by highly metastatic cancer cells versus poorly metastatic counterparts. Surprisingly, genetically depleting periostin+ CAFs slightly accelerated primary tumor growth but impaired intratumoral collagen organization and inhibited lymphatic, but not lung, metastases. Periostin ablation in CAFs impaired their ability to deposit aligned collagen matrices and inhibited cancer cell invasion through collagen and across lymphatic endothelial cell monolayers. Thus, highly metastatic cancer cells mobilize periostin-expressing CAFs in the primary tumor site that promote collagen remodeling and collective cell invasion within lymphatic vessels and ultimately to sentinel lymph nodes.
Significance:
Highly metastatic breast cancer cells activate a population of periostin-expressing CAFs that remodel the extracellular matrix to promote escape of cancer cells into lymphatic vessels and drive colonization of proximal lymph nodes.
Supplementary Tables from Small Gene Networks Delineate Immune Cell States and Characterize Immunotherapy Response in Melanoma
Authors: Egan Donagh , Kreileder Martina , Nabhan Myriam , Iglesias-Martinez Luis F. , Dovedi Simon J. , Valge-Archer Viia , Grover Amit , Wilkinson Robert W. , Slidel Timothy , Bendtsen Claus , Barrett Ian P. , Brennan Donal J. , Kolch Walter , Zhernovkov Vadim
Published: June 2023

Supplementary Tables S1 and S2
Supplemental Figure 9 from Feasibility and Safety of Personalized, Multi-Target, Adoptive Cell Therapy (IMA101): First-in-Human Clinical Trial in Patients with Advanced Metastatic Cancer
Authors: Tsimberidou Apostolia M. , Guenther Kerstin , Andersson Borje S. , Mendrzyk Regina , Alpert Amir , Wagner Claudia , Nowak Anna , Aslan Katrin , Satelli Arun , Richter Fabian , Kuttruff-Coqui Sabrina , Schoor Oliver , Fritsche Jens , Coughlin Zoe , Mohamed Ali S. , Sieger Kerry , Norris Becky , Ort Rita , Beck Jennifer , Vo Henry Hiep , Hoffgaard Franziska , Ruh Manuel , Backert Linus , Wistuba Ignacio I. , Fuhrmann David , Ibrahim Nuhad K. , Morris Van Karlyle , Kee Bryan K. , Halperin Daniel M. , Nogueras-Gonzalez Graciela M. , Kebriaei Partow , Shpall Elizabeth J. , Vining David , Hwu Patrick , Singh Harpreet , Reinhardt Carsten , Britten Cedrik M. , Hilf Norbert , Weinschenk Toni , Maurer Dominik , Walter Steffen
Published: June 2023

Supplemental Figure 9
Figure S6 from Circulating and Intratumoral Immune Determinants of Response to Atezolizumab plus Bevacizumab in Patients with Variant Histology or Sarcomatoid Renal Cell Carcinoma
Authors: Saliby Renee Maria , El Zarif Talal , Bakouny Ziad , Shah Valisha , Xie Wanling , Flippot Ronan , Denize Thomas , Kane M. Harry , Madsen Katrine N. , Ficial Miriam , Hirsch Laure , Wei Xiao X. , Steinharter John A. , Harshman Lauren C. , Vaishampayan Ulka N. , Severgnini Mariano , McDermott David F. , Lee Gwo-Shu Mary , Xu Wenxin , Van Allen Eliezer M. , McGregor Bradley A. , Signoretti Sabina , Choueiri Toni K. , McKay Rana R. , Braun David A.
Published: June 2023

Supplementary Figure 6
Supplemental Figure 10 from Feasibility and Safety of Personalized, Multi-Target, Adoptive Cell Therapy (IMA101): First-in-Human Clinical Trial in Patients with Advanced Metastatic Cancer
Authors: Tsimberidou Apostolia M. , Guenther Kerstin , Andersson Borje S. , Mendrzyk Regina , Alpert Amir , Wagner Claudia , Nowak Anna , Aslan Katrin , Satelli Arun , Richter Fabian , Kuttruff-Coqui Sabrina , Schoor Oliver , Fritsche Jens , Coughlin Zoe , Mohamed Ali S. , Sieger Kerry , Norris Becky , Ort Rita , Beck Jennifer , Vo Henry Hiep , Hoffgaard Franziska , Ruh Manuel , Backert Linus , Wistuba Ignacio I. , Fuhrmann David , Ibrahim Nuhad K. , Morris Van Karlyle , Kee Bryan K. , Halperin Daniel M. , Nogueras-Gonzalez Graciela M. , Kebriaei Partow , Shpall Elizabeth J. , Vining David , Hwu Patrick , Singh Harpreet , Reinhardt Carsten , Britten Cedrik M. , Hilf Norbert , Weinschenk Toni , Maurer Dominik , Walter Steffen
Published: June 2023

Supplemental Figure 10
Figure S5 from Circulating and Intratumoral Immune Determinants of Response to Atezolizumab plus Bevacizumab in Patients with Variant Histology or Sarcomatoid Renal Cell Carcinoma
Authors: Saliby Renee Maria , El Zarif Talal , Bakouny Ziad , Shah Valisha , Xie Wanling , Flippot Ronan , Denize Thomas , Kane M. Harry , Madsen Katrine N. , Ficial Miriam , Hirsch Laure , Wei Xiao X. , Steinharter John A. , Harshman Lauren C. , Vaishampayan Ulka N. , Severgnini Mariano , McDermott David F. , Lee Gwo-Shu Mary , Xu Wenxin , Van Allen Eliezer M. , McGregor Bradley A. , Signoretti Sabina , Choueiri Toni K. , McKay Rana R. , Braun David A.
Published: June 2023

Supplementary Figure 5
Figure S4 from Circulating and Intratumoral Immune Determinants of Response to Atezolizumab plus Bevacizumab in Patients with Variant Histology or Sarcomatoid Renal Cell Carcinoma
Authors: Saliby Renee Maria , El Zarif Talal , Bakouny Ziad , Shah Valisha , Xie Wanling , Flippot Ronan , Denize Thomas , Kane M. Harry , Madsen Katrine N. , Ficial Miriam , Hirsch Laure , Wei Xiao X. , Steinharter John A. , Harshman Lauren C. , Vaishampayan Ulka N. , Severgnini Mariano , McDermott David F. , Lee Gwo-Shu Mary , Xu Wenxin , Van Allen Eliezer M. , McGregor Bradley A. , Signoretti Sabina , Choueiri Toni K. , McKay Rana R. , Braun David A.
Published: June 2023

Supplementary Figure 4
Supplemental Figure 1 from Feasibility and Safety of Personalized, Multi-Target, Adoptive Cell Therapy (IMA101): First-in-Human Clinical Trial in Patients with Advanced Metastatic Cancer
Authors: Tsimberidou Apostolia M. , Guenther Kerstin , Andersson Borje S. , Mendrzyk Regina , Alpert Amir , Wagner Claudia , Nowak Anna , Aslan Katrin , Satelli Arun , Richter Fabian , Kuttruff-Coqui Sabrina , Schoor Oliver , Fritsche Jens , Coughlin Zoe , Mohamed Ali S. , Sieger Kerry , Norris Becky , Ort Rita , Beck Jennifer , Vo Henry Hiep , Hoffgaard Franziska , Ruh Manuel , Backert Linus , Wistuba Ignacio I. , Fuhrmann David , Ibrahim Nuhad K. , Morris Van Karlyle , Kee Bryan K. , Halperin Daniel M. , Nogueras-Gonzalez Graciela M. , Kebriaei Partow , Shpall Elizabeth J. , Vining David , Hwu Patrick , Singh Harpreet , Reinhardt Carsten , Britten Cedrik M. , Hilf Norbert , Weinschenk Toni , Maurer Dominik , Walter Steffen
Published: June 2023

Supplemental Figure 1
Figure S2 from Circulating and Intratumoral Immune Determinants of Response to Atezolizumab plus Bevacizumab in Patients with Variant Histology or Sarcomatoid Renal Cell Carcinoma
Authors: Saliby Renee Maria , El Zarif Talal , Bakouny Ziad , Shah Valisha , Xie Wanling , Flippot Ronan , Denize Thomas , Kane M. Harry , Madsen Katrine N. , Ficial Miriam , Hirsch Laure , Wei Xiao X. , Steinharter John A. , Harshman Lauren C. , Vaishampayan Ulka N. , Severgnini Mariano , McDermott David F. , Lee Gwo-Shu Mary , Xu Wenxin , Van Allen Eliezer M. , McGregor Bradley A. , Signoretti Sabina , Choueiri Toni K. , McKay Rana R. , Braun David A.
Published: June 2023

Supplementary Figure 2
T-cell Therapies Targeting Multiple Cancer Antigens: The Power of Many
Authors: Uslu Ugur , June Carl H.
Published: June 2023

In this issue, Tsimberidou and colleagues report the results of a first-in-human clinical trial using a personalized, multi-target, endogenous T-cell therapy in patients with metastatic solid tumors. This, and results of other recently published clinical trials, confirms the rationale of multi-target approaches that can increase tumor responses and counteract tumor heterogeneity and mechanisms of immune evasion.

See related article by Tsimberidou et al., p. 925 (4).
Supplementary Tables S1-S4 from Sequential chromogenic immunohistochemistry: spatial analysis of lymph nodes identifies contact interactions between plasmacytoid dendritic cells and plasmablasts
Authors: Claudio Natalie , Nguyen My-Tien , Wanner Adrian , Pucci Ferdinando
Published: June 2023

Table S1: Patient characteristics (n=10)
Table S2: Sequential IHC panel information
Table S3: Secondary HRP Round Considerations
Table S4: Comprehensive database information for mIHC panel development
Supplementary Figure S1 from Sequential chromogenic immunohistochemistry: spatial analysis of lymph nodes identifies contact interactions between plasmacytoid dendritic cells and plasmablasts
Authors: Claudio Natalie , Nguyen My-Tien , Wanner Adrian , Pucci Ferdinando
Published: June 2023

Distortion maps. In order to align all the biomarker images for a given sample, each image needs to be corrected for distortions that happen during the staining procedure. This step aims to rectify micro- and macro-anatomical shifts in the tissue sections. Two examples of the calculated shifts (dx, dy and amplitude) and support points for CD3 and CD20.
Supplementary Data from Sequential chromogenic immunohistochemistry: spatial analysis of lymph nodes identifies contact interactions between plasmacytoid dendritic cells and plasmablasts
Authors: Claudio Natalie , Nguyen My-Tien , Wanner Adrian , Pucci Ferdinando
Published: June 2023

Copy of Airtable DB archived at the time of publication
Data from Siglec-15 promotes evasion of adaptive immunity in B-cell acute lymphoblastic leukemia
Authors: Pillsbury Claire E. , Dougan Jodi , Rabe Jennifer L , Fonseca Jairo A , Zhou Chengjing , Evans Alysa N , Abukharma Hasan , Ichoku Ona , Gonzalez-Flamenco Gloria , Park Sunita I. , Aljudi Ahmed , DeRyckere Deborah , Castellino Sharon M , Rafiq Sarwish , Langermann Solomon , Liu Linda N , Henry Curtis J , Porter Christopher C
Published: June 2023

Abstract
Siglec-15 (Sig15) has been implicated as an immune checkpoint expressed in solid tumor-infiltrating macrophages and is being targeted in clinical trials with monoclonal antibodies to normalize the tumor immune microenvironment and stimulate anti-tumor immunity. However, the role of Sig15 in hematological malignancies remains undefined. Sig15 mRNA and protein expression levels in hematological malignancies were determined from publicly available databases, cell lines, and primary patient samples. Human B cell acute lymphoblastic leukemia (B-ALL) cell lines were used to identify signaling pathways involved in the regulation of Sig15 expression. Secreted/soluble Sig15 and cytokine levels were measured from the plasma of children with leukemia and healthy controls. Knockdown and knockout of Siglec15 in a murine model of B-ALL was used to evaluate the effect of leukemia-derived Sig15 on the immune response to leukemia. We observed pathological overexpression of Sig15 in a variety of hematological malignancies, including primary B-ALL samples. This overexpression was driven by NF-κB activation, which also increased the surface localization of Sig15. Secreted/soluble Sig15 was found to circulate at elevated levels in the plasma of children with B-ALL and correlated with an immune-suppressive cytokine milieu. Genetic inhibition of Sig15 in murine B-ALL promoted clearance of the leukemia by the immune system and a marked reversal of the immune-privileged leukemia bone marrow niche, including expanded early effector CD8+ T cells and reduction of immunosuppressive cytokines. Thus, Sig15 is a novel, potent immunosuppressive molecule active in leukemia that may be targeted therapeutically to activate T lymphocytes against leukemia cells.
Data from Sequential chromogenic immunohistochemistry: spatial analysis of lymph nodes identifies contact interactions between plasmacytoid dendritic cells and plasmablasts
Authors: Claudio Natalie , Nguyen My-Tien , Wanner Adrian , Pucci Ferdinando
Published: June 2023

Abstract
Recent clinical observations have emphasized the critical role that the spatial organization of immune cells in lymphoid structures plays in the success of cancer immunotherapy and patient survival. However, implementing sequential chromogenic immunohistochemistry (scIHC) to analyze multiple biomarkers on a single tissue section has been limited due to a lack of a standardized, rigorous guide to the development of customized biomarker panels and a need for user-friendly analysis pipelines that can extract meaningful data. In this context, we provide a comprehensive guide for the development of novel biomarker panels for scIHC, using practical examples and illustrations to highlight the most common complications that can arise during the setup of a new biomarker panel, and provide detailed instructions on how to prevent and detect cross-reactivity between secondary reagents and carryover between detection antibodies. We also developed a novel analysis pipeline based on non-rigid tissue deformation correction, Cellpose-inspired automated cell segmentation, and computational network masking of low-quality data. We applied this biomarker panel and pipeline to study regional lymph nodes from head and neck cancer patients, identifying novel contact interactions between plasmablasts and plasmacytoid dendritic cells in vivo. Given that Toll-like receptors, which are highly expressed in plasmacytoid dendritic cells, play a key role in vaccine efficacy, the significance of this cell-cell interaction decisively warrants further studies. In summary, this work provides a streamlined approach to the development of customized biomarker panels for scIHC that will ultimately improve our understanding of immune responses in cancer.
The Effect of Pearl Oyster (Pinctada maxima L.) Biofouling Waste Organic Fertilizer and Watering Interval on The Growth and Results of Mustard Greens (Brassica juncea L.)
Authors: Nendissa Jeanne Ivonne , Riry Johan , Amba Martha , Soplanit Rudy
Published: June 2023

This research was conducted in Pelita Jaya Village, Pohon Batu Hamlet, West Seram Regency from June to July 2022. The research was conducted to study the effect of the interaction of doses of organic fertilizer from pearl oyster biofouling waste and intervals of water administration on the growth and yield of mustard plants. The design used in this study was a factorial randomized group trial design (RAK) with two treatments as follows: Factor I: Pearl Oyster Biofouling Waste Fertilizer (L) with 4 levels, namely L0 = Control, L1 = Dosage of 50 gr/tan, L = 100 g/tan and L3 = 150 gr/tan Factor II : Watering Time Interval (W) namely W1 = 1 day, W2 = 2 days and W3 = 3 days. Each treatment was combined to obtain 12 treatments with 3 replications, resulting in 36 experimental plots. In each plot, 4 sample plants were taken so that in total there were 144 sample plants. The results of this study indicate that the interaction of organic fertilizer from pearl oyster biofouling waste with intervals of watering has a very significant effect on the growth and yield of mustard plants (number of leaves, leaf area, plant fresh weight and plant dry weight). The best treatment interaction was the combined dose of pearl oyster biofouling waste fertilizer 150 g/tan with an interval of watering once every three days for mustard greens (Brassica juncea L.)
Case Visit Activity Report An. S Patients with Short Stature Pulmonary Tuberculosis Through Family Medicine Approach
Authors: Butar Butar Ananda Josua Triagus Pahala , Sevilla Paulina , Mosso Justhina Ensly , Novendy Novendy
Published: June 2023

Tuberculosis can occur in all age groups adults and children. Tuberculosis (TB) in children occurs in children aged 0-14 years and most common at ages 1-14 years. In the working area of the Cikupa Health Center, there are patients a daughter named An.S who was diagnosed with a new case of pulmonary tuberculosis and has stature short based on results plotting so that need done intervention through family doctor visit. Solving the problem pulmonary tuberculosis infection with short stature in An. S. A female patient, An.S , aged 2 years and 8 months, came with a complaint Cough with fever for 2 weeks. In addition, high growth was also obtained age-appropriate body The patient has received antibiotics and concoction but complaints do not improve. The patient's grandmother also had similar complaints. In this case, an intervention using a family medicine approach with Mandala of Health For get diagnosis holistic And done governance in a manner  comprehensive. After the intervention of An.S showed improvement and is currently undergoing treatment. Height has increased from 84 cm to 86 cm also weight from 11.2 kg to 13 kg. The family has understood about TB disease and is willing to do screening and implement PHBS. Known sources of tuberculosis infection in An. S suspected of coming from the patient's grandmother. TB infection experienced by patients has an impact on inhibiting the patient's growth so that the patient's height does not increase. After comprehensive treatment and education, the patient's family understands tuberculosis, disease transmission and prevention so that it is hoped that the treatment will be carried out completely and can catch up with age-appropriate growth.
The Effect of The Education Background of The Chief Financial Officer and Profitability on Audit Report Lag
Authors: Uzliawati Lia , Muttaqin Galih Fajar , Kurnia Raisa Nur
Published: June 2023

This study aims to determine the effect of the chief financial officer's educational background and profitability on audit report lag. The research object is infrastructure sector companies for the 2018-2021 period. The method in this research is quantitative research with multiple linear regression tests. The sampling technique used is the purposive sampling method. Based on the study's results, (1) CFO's educational background does not affect audit report lag. (2) Profitability has a positive effect on audit report lag. The limitations of this study are the possibility of other independent variables that can explain in more detail the audit report lag phenomenon.