bluuebunny/crossref_metadata_2025 huggingface dataset:
mmSign: mmWave-based Few-Shot Online Handwritten Signature Verification
Authors: Han Mingda , Yang Huanqi , Ni Tao , Duan Di , Ruan Mengzhe , Chen Yongliang , Zhang Jia , Xu Weitao
Published: June 2023

Handwritten signature verification has become one of the most important document authentication methods that are widely used in the financial, legal, and administrative sectors. Compared with offline methods based on static signature images, online handwritten signature verification methods are more reliable because of the temporary dynamic information (e.g., signing velocity, writing force, stroke order) that alleviates the risk of being forged. However, most existing online handwritten signature verification solutions are reliant on specific signing devices (e.g., customized pens or writing pads) and require extensive data collection during the registration phase, resulting in poor adaptability and applicability for new users. In this article, we propose mmSign, a millimeter wave (mmWave)–based online handwritten signature verification system, which enables accurate sensing of the user’s hand movements when signing through the superior sensing capability of mmWave. mmSign extracts the time-velocity feature maps from the captured mmWave signals by the carefully designed signal processing algorithms and then exploits a transformer-based verification model for signature verification. In addition, a novel meta-learning strategy with proposed task generation and data augmentation methods is introduced in mmSign to teach the verification model to learn effectively with limited samples, allowing our model to quickly adapt to new users. Extensive experiments show that mmSign is a robust, efficient, and secure handwritten signature verification system, achieving 84.07%, 87.31%, 91.12%, and 96.54% verification accuracy when 1, 3, 5, and 10 labeled signatures are available, respectively, while being resistant to common forgery attacks.
A Survey of Next-generation Computing Technologies in Space-air-ground Integrated Networks
Authors: Shen Zhishu , Jin Jiong , Tan Cheng , Tagami Atsushi , Wang Shangguang , Li Qing , Zheng Qiushi , Yuan Jingling
Published: June 2023

Space-air-ground integrated networks (SAGINs) are key elements for facilitating high-speed seamless connectivity to the devices/users in infrastructure-less environments, where the traditional terrestrial networks are critically infeasible or uneconomical to be fully deployed. This article comprehensively surveys the advanced computing technologies that support the utilization of SAGINs for infrastructure-less environments. The advanced computing technologies refer to the emerging computing techniques, tools, and the processes that can be utilized to support SAGINs in handling the increasing computing tasks. The main contents include: (1) background of SAGINs, (2) typical use cases of SAGINs in infrastructure-less environments, (3) advanced computing technologies to assist SAGINs to meet the requirements of various services in infrastructure-less environments, (4) the related practical initiatives, and (5) the open research challenges and the future research directions.
The role of Gata3 in renin cell identity
Authors: Neyra Jesus S. , Medrano Silvia , Goes Martini Alexandre De , Sequeira-Lopez Maria Luisa S. , Gomez R. Ariel
Published: June 2023

Gata3, a dual zinc-finger transcription factor, is responsible for the identity and localization of renin cells in the kidney. Mice with a conditional deletion of Gata3 in renin lineage cells have abnormal kidneys with juxtaglomerular cells that lose their characteristic location and are misplaced outside and around arterioles and glomeruli. The fundamental role of Gata3 in renin cell development offers a new model to understand how transcription factors control cell location, function, and pathology.
Muscle metaboreflex control of left ventricular systolic function in heart failure with reduced ejection fraction
Authors: Boyes Natasha G. , Nelson Michael D. , Palmero Canton Alberto , Luchkanych Adam M. S. , Khan M. Rafique , Bare Idris , Haddad Tony , Abdalla Sherif , Marshall Rory A. , Morse Cameron J. , Zhai Alexander , Haddad Haissam , Marciniuk Darcy D. , Karjala Geoffrey , Olver T. Dylan , Tomczak Corey R.
Published: June 2023

Stroke volume decreases and end-systolic volume increases during muscle metaboreflex activation in patients with heart failure with reduced ejection fraction (HFrEF), suggesting impaired contractile reserve during muscle metaboreflex activation in patients with HFrEF. Total peripheral resistance increases similarly during muscle metaboreflex activation in patients with HFrEF compared to controls, indicating normal levels of peripheral vasoconstriction during muscle metaboreflex activation in patients with HFrEF.
A comparison of neural control of the biarticular gastrocnemius muscles between knee flexion and ankle plantar flexion
Authors: Hamard Raphaël , Aeles Jeroen , Avrillon Simon , Dick Taylor J. M. , Hug François
Published: June 2023

Several studies have focused on the neural strategies used to control the gastrocnemius medialis (GM) and lateralis (GL) during plantar flexion. However, their secondary function, i.e., knee flexion, is not often explored. We observed a robustness of the GM and GL activation strategy across tasks, which was confirmed with an analysis of the motor unit discharge characteristics. The level of common synaptic input between GM and GL motor units was low, regardless of the task.
Onset of cardiovascular drift during progressive heat stress in young adults (PSU HEAT project)
Authors: Cottle Rachel M. , Fisher Kat G. , Wolf S. Tony , Kenney W. Larry
Published: June 2023

To our knowledge, this study is the first to 1) identify the specific combinations of temperature and humidity at which an increase in cardiovascular strain (cardiovascular drift) occurs and 2) compare those environments to the critical environmental limits for the maintenance of heat balance. We additionally examined the difference in time between the onset of increased cardiovascular strain and uncompensable heat stress. We show that an increase in cardiovascular strain systematically precedes sustained heat storage in young adults.
The effect of supine cycling and progressive lower body negative pressure on cerebral blood velocity responses
Authors: Miutz Lauren N. , Burma Joel S. , Van Roessel Rowan K. , Johnson Nathan E. , Phillips Aaron A. , Emery Carolyn A. , Brassard Patrice , Smirl Jonathan D.
Published: June 2023

The current investigation demonstrated that moderate-intensity supine cycling-induced increases in cerebral blood velocities were balanced by the lower body negative pressure-induced decreases in cerebral blood velocity. Although performed in a healthy population, the results may lend themselves to a potential treatment option for individuals recovering from concussion or experience persistent concussion symptoms.
Cultivation of Microalgae Spirulina platensis Biomass Using Palm Oil Mill Effluent for Phycocyanin Productivity and Future Biomass Refinery Attributes
Authors: Palanisamy Karthick Murugan , Bhuyar Prakash , Ab. Rahim Mohd Hasbi , Govindan Natanamurugaraj , Maniam Gaanty Pragas
Published: June 2023

Palm oil mill effluent is a type of wastewater which contains a high concentration of organic nitrogen, phosphorus, and different supplement substances. These substances support and enhance the growth of microalgae. Cyanobacteria Spirulina platensis is a blue-green microalga with two phycobiliproteins as its primary constituents. Phycocyanin is a natural blue colourant used in biomedicines, cosmetics, diagnostics, treatments, and environmental protection. Chlorophyll pigment plays a significant role in photosynthesis where the photosynthetic process uses atmospheric carbon to produce starch and lipid which can eventually be converted into desirable products such as biodiesel. Therefore, in this study, Spirulina platensis was cultivated in different concentrations of diluted POME (10-50%,

v
/
v

) at

26
±
1

°C room temperature, 90 μmol photon m-2 s-1, and aerated for 24 h continuously. The growth of Spirulina platensis was monitored through optical density at 680 nm for 15 days. The highest biomass yield obtained in the control medium and 30% POME medium were

1.27
±
0.02

and

1.16
±
0.01

 g/L, respectively. The highest phycocyanin yield obtained from the biomass harvested from 30% nutrient media was

175.12
±
22.32

 mg and followed by

163.55
±
20.15

 mg from control media with purified phycocyanin of

87.11
±
5.20

 mg and

85.31
±
4.33

 mg, respectively. The peak properties of phycocyanin such as the amide group at 1655.17 cm-1 (C=O stretching), FT-IR analysis revealed well-formed Spirulina platensis with all characteristic peaks and distinct fingerprints of phycocyanin. The ultrasound method produces the highest lipid yield (

28.6
±
0.7

%) which consists of stearic (38.45%), palmitoleic (

25.72
±
0.02

), and palmitic (

17.71
±
0.04

) fatty acid methyl esters. The FAME produced from the extracted lipid has the potential to be used in biodiesel applications. Since POME contains the essential nutrients which can support the growth of Spirulina platensis in the optimum environment for biomass and lipid productivity, it revealed the potential for biodiesel production.
Life Cycle Monitoring of Offshore Steel Pipe Piles via UWFBG Wireless Sensor Network
Authors: Wu Jinghong , Xu Shaowen , Qi Le , Meng Zhihao , Jia Lixiang
Published: June 2023

Monitoring the stress and deformation state of offshore steel pipe piles is very necessary for complex ocean environments. However, challenges still remain in remotely capturing detailed data on offshore projects. Herein, an ultraweak fiber Bragg gratings- (UWFBGs-) based wireless sensor network was established to obtain the high-precision strain along the piles. The No. 3 offshore wind power safety monitoring project in South Shandong Peninsula, China, used such a fiber-optic monitoring system. From January 1 to June 1, 2022, strain profiles of three offshore steel pipe piles were measured in seconds with a 1 m spatial resolution and a 1 με strain resolution, which clearly show sea level and mud-water interfaces. To assess the pile’s operational condition, the displacement and rotational angle of the mud surface are further calculated. It is discovered that the horizontal deformation at sea has a positive correlation with the wind, waves, and current, meanwhile decreasing with depth. The UWFBG-wireless sensor network can realize dynamic monitoring and early warning, which is promising for the life cycle monitoring of offshore wind turbine steel pipe piles.
Expectorant Effects of Immature Asian Pear Extract on PM2.5-Induced Subacute Pulmonary Injury in Mice
Authors: Negara Bertoka Fajar Surya Perwira , Kim Joo Wan , Bashir Khawaja Muhammad Imran , Lee Jin-Hwa , Ku Mo-Un , Kim Ki-Young , Shin Su , Hong Eun-Jin , Ku Sae-Kwang , Choi Jae-Suk
Published: June 2023

This study investigated the expectorant effects of immature Asian pear extract (IAP; Pyrus pyrifolia Nakai) on subacute pulmonary injuries in Balb/c mice induced by particulate matter with a diameter of approximately 2.5 μm (PM2.5). IAP was administered at three doses, namely, 400, 200, and 100 mg/kg. The body weight and weight gain changes, lung weights, lung and body surface gross inspections, tracheal secretions, and substance P and ACh content in lung tissue homogenate were observed one day after the tenth IAP administration. The mRNA expression of the genes related to mucus production and lung histopathology was compared with that of the negative and positive controls. Favorable pulmonary protective effects on PM2.5-induced subacute pulmonary injuries, mucus overproduction, and respiratory acidosis were observed in groups treated with IAP at all three doses, possibly through potent anti-inflammatory and mucolytic expectorant activities mediated by the increase in the content of lung substances P and ACh and the downregulation of lung MUC5AC and MUC5B mRNA expression in a dose-dependent manner. The results of this study show that an appropriate oral administration of IAP has sufficient pulmonary protective effects and can be used as a candidate for the development of functional food ingredients.
Resolution-Dependent Multifractal Characteristics of Flow in Digital Rock Twin Simulated Using the Lattice Boltzmann Method
Authors: Tang Han , Dong Yanhui , Wang Xu-Sheng , Wan Li , Jiang Xiao-Wei
Published: June 2023

Digital rock twins are widely used to obtain hydraulic properties of porous media by simulating pore-scale fluid flow. Multifractal characteristics of pore geometry and flow velocity distribution have been discovered with two-dimensional (2D) images and three-dimensional (3D) models, whereas the dependency of results on the resolution is not well known. We investigated resolution-dependent multifractal properties of 3D twin models for a sandstone sample with originally 3 μm resolution images. 3D pore-scale water flow was simulated with the lattice Boltzmann method (LBM). As indicated by multifractal analyses, the generalized dimension spectra, the Hölder exponent spectra, and singularity spectra of the flow velocity are similar to that of the pore geometry but different in ranges and sensitivities to the change in the model resolution. Nonlinear dependencies of 2D/3D porosity, holistic/slice permeability, equivalent pore radius squared, and multifractal parameters on the resolution were discussed.
Supplemental Information from Wnt Signaling Stimulates Cooperation between GREB1 and HNF4α to Promote Proliferation in Hepatocellular Carcinoma
Authors: Matsumoto Shinji , Harada Akikazu , Seta Minami , Akita Masayuki , Gon Hidetoshi , Fukumoto Takumi , Kikuchi Akira
Published: June 2023

Supplementary Methods.
Supplementary References.
Supplemental Figures 1-8 and associated legends.
Supplemental Tables 1-10.
Supplementary Table 2 from N6-Methyladenosine Promotes Translation of VEGFA to Accelerate Angiogenesis in Lung Cancer
Authors: Zhang Haisheng , Zhou Jiawang , Li Jiexin , Wang Zhaotong , Chen Zhuojia , Lv Ziyan , Ge Lichen , Xie Guoyou , Deng Guoming , Rui Yalan , Huang Hongbing , Chen Likun , Wang Hongsheng
Published: June 2023

Table S2
Supplementary 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

Supplementary Data
Table S1 from TGFβ Antagonizes IFNγ-Mediated Adaptive Immune Evasion via Activation of the AKT–Smad3–SHP1 Axis in Lung Adenocarcinoma
Authors: Ye Fan , Cai Zihao , Wang Boyu , Zeng Chenxi , Xi Yu , Hu Shaojie , Qu Rirong , Yuan Zhiwei , Yue Jiaqi , Tian Yitao , Wang Xue , Fu Xiangning , Li Lequn
Published: June 2023

Table S1
Supplementary Data from TGFβ Antagonizes IFNγ-Mediated Adaptive Immune Evasion via Activation of the AKT–Smad3–SHP1 Axis in Lung Adenocarcinoma
Authors: Ye Fan , Cai Zihao , Wang Boyu , Zeng Chenxi , Xi Yu , Hu Shaojie , Qu Rirong , Yuan Zhiwei , Yue Jiaqi , Tian Yitao , Wang Xue , Fu Xiangning , Li Lequn
Published: June 2023

Figure S
Supplementary Data 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

Supplementary Figures S1-S7
Table S4 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

No difference in DCAF7 expression levels in MEN1 wildtype vs mutant samples
Supplementary Information 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 Information:Supplementary Figures 1-6 with Figure Legends, Supplementary Table 1 (reference only), Supplementary Table 2, Supplementary Methods, Supplementary References
Table 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

Clinicopathologic parameters of 50 PanNET patients
Table S1 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

Clinicopathologic parameters according to the expression of NAE1, Ubc12, Rbx1 and global NEDD8 conjugation
Figure S1 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 LPENYTDETWQK peptide from CUL4B as determined by IP-Mass Spec
Supplementary Table 3_Clonal distribution analysis 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 the information about Clonal distribution analysis
Supplementary Table 10_Pro metastatic pathways identified by classification analysis 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 classification analysis
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

Abstract
Adrenocortical carcinoma (ACC) is a rare cancer in which tissue-specific differentiation is paradoxically associated with dismal outcomes. The differentiated ACC subtype CIMP-high is prevalent, incurable, and routinely fatal. CIMP-high ACC possess abnormal DNA methylation and frequent β-catenin–activating mutations. Here, we demonstrated that ACC differentiation is maintained by a balance between nuclear, tissue-specific β-catenin–containing complexes, and the epigenome. On chromatin, β-catenin bound master adrenal transcription factor SF1 and hijacked the adrenocortical super-enhancer landscape to maintain differentiation in CIMP-high ACC; off chromatin, β-catenin bound histone methyltransferase EZH2. SF1/β-catenin and EZH2/β-catenin complexes present in normal adrenals persisted through all phases of ACC evolution. Pharmacologic EZH2 inhibition in CIMP-high ACC expelled SF1/β-catenin from chromatin and favored EZH2/β-catenin assembly, erasing differentiation and restraining cancer growth in vitro and in vivo. These studies illustrate how tissue-specific programs shape oncogene selection, surreptitiously encoding targetable therapeutic vulnerabilities.
Significance:
Oncogenic β-catenin can use tissue-specific partners to regulate cellular differentiation programs that can be reversed by epigenetic therapies, identifying epigenetic control of differentiation as a viable target for β-catenin–driven cancers.
Whole Slide Imaging-Based Prediction of TP53 Mutations Identifies an Aggressive Disease Phenotype in Prostate Cancer
Authors: Pizurica Marija , Larmuseau Maarten , Van der Eecken Kim , de Schaetzen van Brienen Louise , Carrillo-Perez Francisco , Isphording Simon , Lumen Nicolaas , Van Dorpe Jo , Ost Piet , Verbeke Sofie , Gevaert Olivier , Marchal Kathleen
Published: June 2023

In prostate cancer, there is an urgent need for objective prognostic biomarkers that identify the metastatic potential of a tumor at an early stage. While recent analyses indicated TP53 mutations as candidate biomarkers, molecular profiling in a clinical setting is complicated by tumor heterogeneity. Deep learning models that predict the spatial presence of TP53 mutations in whole slide images (WSI) offer the potential to mitigate this issue. To assess the potential of WSIs as proxies for spatially resolved profiling and as biomarkers for aggressive disease, we developed TiDo, a deep learning model that achieves state-of-the-art performance in predicting TP53 mutations from WSIs of primary prostate tumors. In an independent multifocal cohort, the model showed successful generalization at both the patient and lesion level. Analysis of model predictions revealed that false positive (FP) predictions could at least partially be explained by TP53 deletions, suggesting that some FP carry an alteration that leads to the same histological phenotype as TP53 mutations. Comparative expression and histologic cell type analyses identified a TP53-like cellular phenotype triggered by expression of pathways affecting stromal composition. Together, these findings indicate that WSI-based models might not be able to perfectly predict the spatial presence of individual TP53 mutations but they have the potential to elucidate the prognosis of a tumor by depicting a downstream phenotype associated with aggressive disease biomarkers.

Significance:

Deep learning models predicting TP53 mutations from whole slide images of prostate cancer capture histologic phenotypes associated with stromal composition, lymph node metastasis, and biochemical recurrence, indicating their potential as in silico prognostic biomarkers.

See related commentary by Bordeleau, p. 2809
SENP1 Decreases RNF168 Phase Separation to Promote DNA Damage Repair and Drug Resistance in Colon Cancer
Authors: Wei Min , Huang Xinping , Liao Liming , Tian Yonglu , Zheng Xiaofeng
Published: June 2023

The DNA damage response (DDR) is essential for the maintenance of genomic stability. Protein posttranslational modifications play pivotal roles in regulating the DDR process. Here, we found that SUMOylated RNF168 undergoes liquid–liquid phase separation (LLPS), which restricts the recruitment of RNF168 to DNA damage sites, reduces RNF168-catalyzed H2A ubiquitination, restrains 53BP1 in nuclear condensates, and ultimately impairs nonhomologous DNA end joining repair efficiency. Sentrin/SUMO-specific protease 1 (SENP1) was identified as a specific deSUMOylase of RNF168, and it was highly expressed in colorectal adenocarcinoma. In response to DNA damage, SENP1 decreased RNF168 SUMOylation and prevented RNF168 from forming nuclear condensates, thus promoting damage repair efficiency and cancer cell resistance to DNA damaging agents. Moreover, high SENP1 expression correlated with poor prognosis in patients with cancer, and SENP1 depletion sensitized cancer cells to chemotherapy. In summary, these findings reveal DDR is suppressed by SUMOylation-induced LLPS of RNF168 and suggest that SENP1 is a potential target for cancer therapy.

Significance:

Sentrin/SUMO-specific protease 1 decreases RNF168 SUMOylation and liquid–liquid phase separation to promote DNA damage repair, safeguarding genomic integrity and driving chemotherapy resistance.
Targeting Upregulated cIAP2 in SOX10-Deficient Drug Tolerant Melanoma
Authors: Glasheen McKenna Q. , Caksa Signe , Young Amelia G. , Wilski Nicole A. , Ott Connor A. , Chervoneva Inna , Flaherty Keith T. , Herlyn Meenhard , Xu Xiaowei , Aplin Andrew E. , Capparelli Claudia
Published: June 2023

Drug tolerance and minimal residual disease (MRD) are likely to prelude acquired resistance to targeted therapy. Mechanisms that allow persister cells to survive in the presence of targeted therapy are being characterized but selective vulnerabilities for these subpopulations remain uncertain. We identified cellular inhibitor of apoptosis protein 2 (cIAP2) as being highly expressed in SOX10-deficient drug tolerant persister (DTP) melanoma cells. Here, we show that cIAP2 is sufficient to induce tolerance to MEK inhibitors, likely by decreasing the levels of cell death. Mechanistically, cIAP2 is upregulated at the transcript level in SOX10-deficient cells and the AP-1 complex protein, JUND, is required for its expression. Using a patient-derived xenograft model, we demonstrate that treatment with the cIAP1/2 inhibitor, birinapant, during the MRD phase delays the onset of resistance to BRAF inhibitor and MEK inhibitor combination therapy. Together, our data suggest that cIAP2 upregulation in SOX10-deficient subpopulations of melanoma cells induces drug tolerance to MAPK targeting agents and provides a rationale to test a novel therapeutical approach to target MRD.
HCK Promotes High-Grade Serous Ovarian Cancer Tumorigenesis through CD44 and NOTCH3 Signaling
Authors: Khella Christen A. , Franciosa Lucyann , Rodirguez-Rodriguez Lorna , Rajkarnikar Resha , Mythreye Karthikeyan , Gatza Michael L.
Published: June 2023

High-grade serous ovarian cancer (HGSOC) is a highly aggressive and lethal subtype of ovarian cancer. While most patients initially respond to standard-of-care treatment, the majority will eventually relapse and succumb to their disease. Despite significant advances in our understanding of this disease, the mechanisms that govern the distinctions between HGSOC with good and poor prognosis remain unclear. In this study, we implemented a proteogenomic approach to analyze gene expression, proteomic and phosphoproteomic profiles of HGSOC tumor samples to identify molecular pathways that distinguish HGSOC tumors relative to clinical outcome. Our analyses identify significant upregulation of hematopoietic cell kinase (HCK) expression and signaling in poor prognostic HGSOC patient samples. Analyses of independent gene expression datasets and IHC of patient samples confirmed increased HCK signaling in tumors relative to normal fallopian or ovarian samples and demonstrated aberrant expression in tumor epithelial cells. Consistent with the association between HCK expression and tumor aggressiveness in patient samples, in vitro phenotypic studies showed that HCK can, in part, promote cell proliferation, colony formation, and invasive capacity of cell lines. Mechanistically, HCK mediates these phenotypes, partly through CD44 and NOTCH3-dependent signaling, and inhibiting CD44 or NOTCH3 activity, either genetically or through gamma-secretase inhibitors, can revert HCK-driven phenotypes.

Implications:

Collectively, these studies establish that HCK acts as an oncogenic driver of HGSOC through aberrant activation of CD44 and NOTCH3 signaling and identifies this network as a potential therapeutic opportunity in a subset of patients with aggressive and recurrent HGSOC.
Data from Splicing Factor SRSF1 Promotes Pancreatitis and KRASG12D-Mediated Pancreatic Cancer
Authors: Wan Ledong , Lin Kuan-Ting , Rahman Mohammad Alinoor , Ishigami Yuma , Wang Zhikai , Jensen Mads A. , Wilkinson John E. , Park Youngkyu , Tuveson David A. , Krainer Adrian R.
Published: June 2023

Abstract
Inflammation is strongly associated with pancreatic ductal adenocarcinoma (PDAC), a highly lethal malignancy. Dysregulated RNA splicing factors have been widely reported in tumorigenesis, but their involvement in pancreatitis and PDAC is not well understood. Here, we report that the splicing factor SRSF1 is highly expressed in pancreatitis, PDAC precursor lesions, and tumors. Increased SRSF1 is sufficient to induce pancreatitis and accelerate KRASG12D-mediated PDAC. Mechanistically, SRSF1 activates MAPK signaling—partly by upregulating interleukin 1 receptor type 1 (IL1R1) through alternative-splicing-regulated mRNA stability. Additionally, SRSF1 protein is destabilized through a negative feedback mechanism in phenotypically normal epithelial cells expressing KRASG12D in mouse pancreas and in pancreas organoids acutely expressing KRASG12D, buffering MAPK signaling and maintaining pancreas cell homeostasis. This negative feedback regulation of SRSF1 is overcome by hyperactive MYC, facilitating PDAC tumorigenesis. Our findings implicate SRSF1 in the etiology of pancreatitis and PDAC, and point to SRSF1-misregulated alternative splicing as a potential therapeutic target.
Significance:
We describe the regulation of splicing factor SRSF1 expression in the context of pancreas cell identity, plasticity, and inflammation. SRSF1 protein downregulation is involved in a negative feedback cellular response to KRASG12D expression, contributing to pancreas cell homeostasis. Conversely, upregulated SRSF1 promotes pancreatitis and accelerates KRASG12D-mediated tumorigenesis through enhanced IL1 and MAPK signaling.
Supplementary Figures and Tables 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

Supplementary Figure Legends and Tables
Supplementary Figures 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 Figures S1 and S2
Supplemental Figure 8 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 8
Table 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 table 2
Supplemental Figure 7 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 7
Supplemental Figure 6 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 6
Supplementary Data 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

Titles and captions of supplementary figures
Figure S9 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 9
Figure S8 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 8
Supplemental Figure 3 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 3
Figure S7 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 7
Supplemental Figure 2 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 2
Figure S3 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 3
Figure S11 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 11
Supplementary Figure 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

Avoid cross-reactivity of secondary reagents. Using a horse anti-rabbit (see Figure 5) to detect IgG1 (A) or CD11c (B) in round 1 does not lead to cross reactivity with the rabbit anti-goat secondary reagent used in the next round to detect BDCA2 and IgA, respectively.
Supplementary Figure S2 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

Alignment results. Comparison of before and after alignment for CD3 (red, top) and CD20 (red, bottom) superimposed with hematoxylin (green).
Acral Melanocytic Nevi in a High-Risk Population: Prevalence, Clinical Characteristics and Dermatoscopic Patterns
Authors: Papageorgiou Chryssoula , Kyrgidis Athanassios , Ilut Paula Anca , Gkentsidi Theodosia , Manoli Sofia-Magdalini , Camela Elisa , Apalla Zoe , Lallas Aimilios
Published: June 2023

Background: The prevalence of acral nevi and their dermatoscopic patterns have been mainly studied in Asian populations. Few data exist on the prevalence and clinico-dermatoscopic morphology of acral nevi in white populations. Objectives: The aim of this study was to assess the prevalence of acral nevi and evaluate their features in a cohort of Caucasian individuals at high risk for skin cancer. Methods: We prospectively examined the palms and soles of 680 high-risk patients who underwent total body clinical and dermatoscopic documentation, as a part of their routine follow-up, between January 2016 and March 2020 at a skin cancer referral center in Greece. Results: Overall, 334 acral lesions were detected in 217 (37.0%) of 585 patients in the study. The presence of acral nevi was associated with 2.6 higher odds of a total nevus count higher than 50 (OR: 2.6, p < 0.05, confidence intervals [CI]: 1.11–6.09). Of 334 acral nevi, 65.0% were clinically flat and 35.0% were clinically palpable. Palpable lesion had 19-fold higher probability of being located on the sole (OR: 19.44, p < 0.05, CI: 3.91–96.7). The parallel furrow pattern was present in 147 lesions (44.0%). In 76 lesions (22.8%), we observed a previously undefined pattern consisting of wavy lines, which was correlated with clinically palpable lesions (p < 0.001). The third most common pattern was homogeneous (10.5%), followed by the fibrillar (8.7%), the lattice-like (7.2%), the reticular (3.6%), and globular (3.3%). Conclusion: We observed a higher prevalence of benign acral melanocytic lesions than expected, probably related to our cohort selection of patients at high risk for developing skin cancer. Our study confirms the previously described dermatoscopic patterns and provides novel insights into the dermatoscopic morphology of acral palpable nevi, for which we described a new benign pattern consisting of wavy lines.
Perceptions, Challenges and Effectiveness of Modular Distance Learning Approach to The Academic Performance of Humanities and Social Sciences (HUMSS) Students of Botolan National High School
Authors: De Ocampo Norvin D.
Published: June 2023

The COVID-19 pandemic has necessitated a significant shift towards modular distance learning in education systems worldwide. In the Philippines, the Department of Education has developed Self-Learning Modules (SLMs) to ensure quality primary education for all learners during the pandemic. This research study aims to identify the challenges and effectiveness of the modular distance learning approach on the academic performance of Grade 12 Humanities and Social Sciences students at Botolan National High School. Employing a descriptive research design, data were collected through a validated questionnaire and analyzed using weighted arithmetic mean, frequency, percentage distribution, and Pearson-r correlation. The study found that the majority of student-respondents were female, aged 17.31 years old, and achieved very satisfactory academic grades. The students perceived the modular distance learning approach as agreeable, with self-motivation being the most challenging aspect. The ability to express ideas was the most effective aspect, while the ability to answer without pressure was the least effective. The study found no significant relationship between student's perceptions of the modular distance learning approach and their academic performance. Based on the findings, the study recommends using the modular distance learning approach and developing policies to address students' mental health issues. Furthermore, further research is needed to investigate teacher readiness and technology competency, as well as other variables not covered in this study, to improve the effectiveness of the modular distance learning approach. The study demonstrates that despite the limitations caused by the pandemic, modular distance learning can be an efficient alternative to traditional face-to-face education.