bluuebunny/crossref_metadata_2025 huggingface dataset:
Quantifying the impact of immunotherapy on RNA dynamics in cancer
Authors: Usaite Ieva , Biswas Dhruva , Dijkstra Krijn , Watkins Thomas BK , Pich Oriol , Puttick Clare , Angelova Mihaela , Thakkar Krupa , Hiley Crispin , Birkbak Nicolai , Kok Marleen , Zaccaria Simone , Wu Yin , Litchfield Kevin , Swanton Charles , Kanu Nnennaya
Published: November 2023

Background

Checkpoint inhibitor (CPI) immunotherapies have provided durable clinical responses across a range of solid tumor types for some patients with cancer. Nonetheless, response rates to CPI vary greatly between cancer types. Resolving intratumor transcriptomic changes induced by CPI may improve our understanding of the mechanisms of sensitivity and resistance.

Methods

We assembled a cohort of longitudinal pre-therapy and on-therapy samples from 174 patients treated with CPI across six cancer types by leveraging transcriptomic sequencing data from five studies.

Results

Meta-analyses of published RNA markers revealed an on-therapy pattern of immune reinvigoration in patients with breast cancer, which was not discernible pre-therapy, providing biological insight into the impact of CPI on the breast cancer immune microenvironment. We identified 98 breast cancer-specific correlates of CPI response, including 13 genes which are known IO targets, such as toll-like receptorsTLR1,TLR4, andTLR8, that could hold potential as combination targets for patients with breast cancer receiving CPI treatment. Furthermore, we demonstrate that a subset of response genes identified in breast cancer are already highly expressed pre-therapy in melanoma, and additionally we establish divergent RNA dynamics between breast cancer and melanoma following CPI treatment, which may suggest distinct immune microenvironments between the two cancer types.

Conclusions

Overall, delineating longitudinal RNA dynamics following CPI therapy sheds light on the mechanisms underlying diverging response trajectories, and identifies putative targets for combination therapy.
Distinction and prognosis of early arthritis phenotypes: an analysis in three European cohorts
Authors: Sepriano Alexandre , van Dijk Bastiaan , Ramiro Sofia , van der Helm-van Mil Annette , Combe Bernard , van Schaardenburg Dirkjan , de Wit Maarten , Kent Alison , Mateus Elsa , Landewé Robert
Published: November 2023

Objectives

The objective of this study is to evaluate whether there are differences in the long-term prognosis across various phenotypes of early arthritis (EA).

Methods

Three EA cohorts (Reade, Etude et Suivi des Polyarthrites Indifférenciées Récentes (ESPOIR) and Early Arthritis Clinic (EAC)) were analysed. Clinical data were collected up to 24 years. Hands and feet radiographs were scored according to the Sharp van der Heijde (SvdH) method. Latent class analysis was applied to determine the EA phenotypes at baseline. Each class received a label reflecting its most prominent features. Prognostic outcomes included Health Assessment Questionnaire (HAQ), Short Form 36 (SF36) and SvdH score. The association between class membership and outcomes over time was tested in multivariable models.

Results

In total, 390 (Reade), 798 (ESPOIR) and 3991 (EAC) patients were analysed separately. Two classes with symmetrical polyarthritis emerged; one of these labelled as autoimmune inflammatory polyarthritis (AIPA), had high likelihood of acute phase reactants (APR) elevation and autoantibody positivity, while the other (mild-inflammatory polyarthritis; MIPA) had not. A third class had oligoarthritis of upper limbs (OAUL) and could be subdivided into autoimmune OAUL and mild-inflammatory OAUL. A fifth class had oligoarthritis of lower limbs. The SvdH scores were worse in patients with APR/autoantibodies (AIPA) than in those without (MIPA). No clinically meaningful differences across classes in HAQ or SF36 over time were found.

Conclusion

Radiographic progression over time primarily occurs in EA patients with APR/autoantibodies. The absence of these markers, however, does not necessarily translate into better long-term function and quality of life. Clinicians should not only aim at preventing joint damage, but look beyond structural progression in order to further improve the lives of people with EA.
Factors associated with compartment syndrome after a tibial fracture in children
Authors: Ahmed Nasim , Kuo Yen-Hong
Published: November 2023

Objectives

Compartment syndrome (CS) after a tibial fracture in children is one of the orthopedic emergencies. Identifying high-risk patients in a timely fashion minimizes morbidities. This study aimed to find the risk factors of CS after a tibial fracture.

Methods

The study data was retrieved from the Trauma Quality Improvement Program database of the calendar year 2017–2019. All patients aged <18 years old who were admitted to the hospital with tibial fractures were included in the study. Patients’ characteristics, including demography, injury, injury severity, and associated crushed and vascular injuries were analyzed between the groups who developed CS versus those who did not develop CS after a tibial fracture. Multiple logistic regression analyses were performed to find the association of CS. All p values are two-sided and a p value<0.05 is considered statistically significant.

Results

Of 4492 patients who qualified for the study, 49 (1.1%) patients developed CS. The patients who developed CS sustained more crush injuries and were associated with a higher rate of vascular injury (2% vs 0.1%, p=0.043% & 10.2% vs 2.2%, p=0.005). Multivariable analysis showed that for every increase in 1 year of age, the odds of occurrence of CS increased by 15.7% (adjusted OR (AOR)=1.157, 95% CI: 1.032 to 1.297, p=0.013). Non-African American race was associated with more than double the risk of developing CS when compared with the African American race, AOR was 2.238, (95% CI: (1.08 to 4.638)). The associated crush injury had an approximately 19-fold higher risk of CS when compared with patients presented with no crush injury, AOR was 18.812, (95% CI: (1.513 to 233.931)). Associated vascular injury was found to have significantly higher AOR, 3.509, 95% CI: (1.287 to 9.563) of CS.

Conclusion

Increased age, non-African American race, vascular injury, and crushed injury were associated with a risk of developing CS after a tibial fracture.

Level of evidence: IV

Study type: Observational cohort study.
Study of the modulational instability and miscellaneous soliton for metamaterials via three powerful schemes
Authors: Li Yanning , Manafian Jalil , Takami S. F. S. , Shatouri Z. M. , Alenizi F. A. , Alawadi A. H. , Alsaalamy A.
Published: November 2023

In this paper, the exact solitary wave solutions for the generalized nonlinear (NL) Schrödinger equation with parabolic NL law employing the generalized [Formula: see text]-expansion technique, the improved [Formula: see text]-expansion technique and the modified exp-function technique are acquired. Different sets of exponential function solutions are acquired relying on a map between the considered equation and an auxiliary ordinary differential equation (ODE). The obtained solutions are concluded in several of the hyperbolic and trigonometric forms based on diverse restrictions between parameters involved in equations and integration constants that appear in the solution. A few significant ones among the reported solutions are pictured to perceive the physical utility and peculiarity of the considered model utilizing mathematical software. For more analysis, the modulation instability (MI) analysis of the proposed model with normal derivatives is also carried out for parabolic NL law. The main aim of this research is that one can visualize and update the knowledge to overcome from the most common methods to solve the ODEs and partial differential equations (PDEs). We demonstrated that these solutions validated the program using Maple and found them to be correct. The proposed methodology for resolving NLPDEs has been designed to be effectual, unpretentious, expedient, and manageable. Finally, the existence of the solutions for the constraint conditions is also shown.
Investigation on Aerodynamic Fluid–Structure Coupling Vibration of 160 km/h EMU Tail in Single-Track Tunnels
Authors: Song Yadong , Qin Ting , Yao Yuan , Dai Fengyu
Published: November 2023

Recently, the phenomenon of tail-sustained swaying of the 160[Formula: see text]km/h EMU in single-track tunnels has gained much attention, especially for the rear-powered vehicle. This phenomenon is investigated from the perspective of aerodynamic fluid–structure coupling vibration in this study. The aerodynamics simulation model of the train in tunnels and the multi-body dynamics model of the rear-powered vehicle were respectively established through the software of XFlow and Simpack, and then the fluid–structure coupling vibration was simulated by using real-time data dynamic exchange between the two models. Moreover, the carbody’s vibration acceleration and the aerodynamic loads acting on the carbody under various wheel–rail contact geometrical conditions were discussed. Finally, the train tail swaying in field was tested, and the dominant frequencies were analyzed. The results show that the periodic aerodynamic loads and the frequency locking effect caused by the coupled vibration are the main factors for ride comfort deterioration. The violent vibration caused by fluid–structure coupling is named vortex-induced vibration (VIV) in some industries such as bridge and submarine pipeline. For the vehicle in this work, with the decrease of equivalent conicity in wheel–rail contact, the amplitude of carbody swaying increases owing to the carbody hunting, which enhances the fluid–structure coupling vibration, and further deteriorates the ride comfort. The swaying of the carbody is dominated by the vehicle hunting frequency, and the improvement of vehicle lateral stability can weaken this phenomenon.
Fusion rules for the orbifold vertex operator algebras L𝔰𝔩2 ̂(k,0)K
Authors: Iqbal Rabia , Jiang Cuipo
Published: November 2023

For the Klein group [Formula: see text] and a positive integer [Formula: see text], irreducible modules of the orbifold vertex operator algebra [Formula: see text] have been classified and constructed in [C. Jiang and B. Wang, Representations of the orbifold VOAS [Formula: see text] and the commutant VOAS [Formula: see text], Bull. Malays. Math. Sci. Soc. 44(1) (2021) 353–373]. In this paper, we determine completely the fusion rules of [Formula: see text].
IDENTIFYING VITAL NODES IN COMPLEX NETWORK BY CONSIDERING MULTIPLEX INFLUENCES
Authors: REN TAO , XU YANJIE , LIU LINGJUN , GUO ENMING , WANG PENGYU
Published: November 2023

Identifying vital nodes is a fundamental topic in network science. Some methods are proposed to identify vital nodes in a complex network. These measures take into account different aspects of a node’s importance, such as its number of connections, the centrality of its connected nodes, and the distribution of its connections. Applying these measures makes it is possible to identify the nodes that play a vital role in the network and that have the greatest impact on its structure and function. However, there is still an inherent problem with identifying vital nodes accurately and discriminatively. To address the problem, for undirected unweighted networks, we propose an algorithm based on the nodes’ multiplex influences via the network structure to identify vital nodes. The effectiveness of the proposed method is evaluated by Kendall’s Tau ([Formula: see text]) and monotonicity and compared with well-known existing metrics such as degree centrality, K-shell decomposition, H-index, betweenness centrality, closeness centrality, eigenvector centrality, collective influence, and gravity model in 10 real networks. Experimental results show the superiority of the proposed algorithm in identifying vital nodes.
A robust, flow-based, microfluidic device for siRNA-mediated gene knockdown in glioblastoma spheroids
Authors: Hosni Ines , Iles Alex , Greenman John , Wade Mark A.
Published: November 2023

Glioblastoma (GBM) is a deadly disease with a poor prognosis, there is therefore a crucial need for novel therapeutic targets. Current preclinical models of GBM fail to predict clinical outcomes, thus, new translationally relevant models are urgently needed for reliable therapeutic target validation. 3D spheroid culture of cancer cells has been shown to better reflect tumour biology than 2D monolayer culture, as has culturing cells in flow-based microfluidic devices, which mimic key aspects of the tumour microenvironment. Gene knockdown by siRNA is a key preclinical target validation tool, however, siRNA-mediated knockdown of cancer spheroids in microfluidic culture has not yet been demonstrated. Here we describe a simple and robust microfluidic device that can maintain GBM spheroids (U87 cells) for at least 7 days. Via RNA sequencing analysis, we demonstrate that spheroids grown in microfluidic culture are more proliferative than spheroids grown in static plate culture and downregulate genes associated with cell adhesion, potentially offering insights into the metastatic process. Comparison of target gene (PRMT2 and RAB21) knockdown using siRNA between 2D monolayer cultured cells, static spheroid culture and spheroids maintained in the microfluidic device showed that gene expression (as measured by quantitative-PCR) was significantly reduced in all culture systems. Knockdown was most efficient in cells grown in 2D monolayer culture followed by static spheroid culture, but we also demonstrate [Formula: see text] knockdown efficiency using the microfluidic device. In summary, this study describes an easy-to-use microfluidic culture platform and provides evidence that pre-clinical siRNA-mediated target validation studies will be possible in flow systems that mimic tumour physiology.
BrickStARt: Enabling In-situ Design and Tangible Exploration for Personal Fabrication using Mixed Reality
Authors: Stemasov Evgeny , Hohn Jessica , Cordts Maurice , Schikorr Anja , Rukzio Enrico , Gugenheimer Jan
Published: November 2023

3D-printers enable end-users to design and fabricate unique physical artifacts but maintain an increased entry barrier and friction. End users must design tangible artifacts through intangible media away from the main problem space (ex-situ) and transfer spatial requirements to an abstract software environment. To allow users to evaluate dimensions, balance, or fit early and in-situ, we developed BrickStARt, a design tool using tangible construction blocks paired with a mixed-reality headset. Users assemble a physical block model at the envisioned location of the fabricated artifact.
Designs can be tested tangibly, refined, and digitally post-processed, remaining continuously in-situ. We implemented BrickStARt using a Magic Leap headset and present walkthroughs, highlighting novel interactions for 3D-design. In a user study (n=16), first-time 3D-modelers succeeded more often using BrickStARt than Tinkercad. Our results suggest that BrickStARt provides an accessible and explorative process while facilitating quick, tangible design iterations that allow users to detect physics-related issues (e.g., clearance) early on.
BlendMR: A Computational Method to Create Ambient Mixed Reality Interfaces
Authors: Han Violet Yinuo , Cho Hyunsung , Maeda Kiyosu , Ion Alexandra , Lindlbauer David
Published: November 2023

Mixed Reality (MR) systems display content freely in space, and present nearly arbitrary amounts of information, enabling ubiquitous access to digital information. This approach, however, introduces clutter and distraction if too much virtual content is shown. We present BlendMR, an optimization-based MR system that blends virtual content onto the physical objects in users’ environments to serve as ambient information displays. Our approach takes existing 2D applications and meshes of physical objects as input. It analyses the geometry of the physical objects and identifies regions that are suitable hosts for virtual elements. Using a novel integer programming formulation, our approach then optimally maps selected contents of the 2D applications onto the object, optimizing for factors such as importance and hierarchy of information, viewing angle, and geometric distortion. We evaluate BlendMR by comparing it to a 2D window baseline. Study results show that BlendMR decreases clutter and distraction, and is preferred by users. We demonstrate the applicability of BlendMR in a series of results and usage scenarios.
Prediction of Postoperative Acute Kidney Injury Risk Factors for Acute Type A Aortic Dissection Patients after Modified Triple-Branched Stent Graft Implantation by a Perioperative Nomogram: A Retrospective Study
Authors: Xu Fan , Xie Linfeng , He Jian , Wu Qingsong , Lin Xinfan , Hu Yunnan , Chen Liangwan
Published: November 2023

Objective. Predicting risk factors for acute kidney injury (AKI) after total arch replacement via modified triple-branched stent graft (MTBSG) implantation in patients with acute type A aortic dissection (AAAD) by conducting a nomogram. Methods. We collected the clinical data of 254 patients with AAAD who underwent MTBSG implantation surgery in our center. The independent risk factors of postoperative AKI were screened by univariate and multivariate logistic regression analysis and combined into a nomogram. We use receiver operating characteristic (ROC) curves, decision curve analysis (DCA), clinical impact curve (CIC), and calibration plots to evaluate the accuracy of the nomogram model. Results. Multiple logistic regression analysis showed that the risk factors of AKI after MTBSG implantation were age, malperfusion syndrome, preoperative serum creatinine, cardiopulmonary bypass time, and amount of red blood cell (RBC) transfusion. Based on these five risk factors, we established a nomogram model. The good accuracy and clinical applicability of the model were verified by drawing ROC curve (area under the curve (AUC) = 0.854), DCA curve, CIC curve, and calibration curve. Conclusions. Using perioperative clinical data to establish a nomogram model of AKI in patients with AAAD who received MTBSG implantation can be used as a tool to predict the occurrence of AKI after operation.
Pharmacogenetic Approach for the Prevention of Rivaroxaban’s ADRs: A Systematic Review and Meta-Analysis
Authors: Mardi Parham , Abbasi Bahareh , Shafiee Arman , Afsharmoghaddam Tara
Published: November 2023

Introduction. Pharmacogenetics is a potential approach that can be applied to decline the burden of rivaroxaban’s ADRs. The current systematic review and meta-analysis aim to identify genetic variants correlated with rivaroxaban exposure and evaluate their importance. Methods. We systematically searched PubMed, Web of Science, and Scopus databases for all observational and interventional studies. The fixed effect method was used to pool the data when the Q-test’spvalue was higher than 0.1. We used random models when thepvalue was less than 0.1. Results. Data from ten studies (4721 participants) were analyzed in the current review. Qualitative synthesis from included studies found that two variants of ABCB1 (rs1045642 and rs2032582) and one variant of APOB (rs13306198) are potential contributors to rivaroxaban concentrations. Both wild homozygotes (AA) and heterozygotes (AC) of rs1045642 have significantly lower rivaroxaban concentrations compared to mutated homozygotes (CC) (SMD = 0.516, 95% CI: 0.115 to 0.917; SMD = 0.772, 95% CI: 0.088 to 1.455, respectively). Nevertheless, pooling unadjusted odds ratios did not yield a statistically significant correlation between rivaroxaban ADRs and genetic mutations. Conclusion. This study revealed that being an AC or CC for rs1045642 is attributed to a considerably higher rivaroxaban level in participants using rivaroxaban. That is to say, rs1045642 is a remarkable predictor of rivaroxaban metabolism. We concluded that identifying rs1045642 before drug administration might decrease ADRs although further studies adjusted for potential confounders are strongly suggested.
Daily Living and Healthcare Experiences of Individuals Living with Desmoid-Type Fibromatosis: A Qualitative Investigation
Authors: Bowes Megan , Coyle Catherine , Husson Olga , Dienes Kimberly , Powell Rachael
Published: November 2023

Objective. Desmoid-type fibromatosis (DF), a rare benign tumour with similar treatment options to cancer, can adversely impact people’s lives, yet little qualitative research addressing patients’ experiences of DF exists. The present study aimed to understand the day-to-day experiences of individuals with DF and their experiences of healthcare. Methods. Semistructured, qualitative interviews were conducted by phone or email with 20 participants. Inductive thematic analysis was performed, structured with the Framework approach. Results. Many participants reported delays in diagnosis. This was attributed to them ignoring their symptoms or to healthcare professionals lacking awareness of DF. Healthcare experiences varied, with some participants expressing good support. Others felt unsupported, viewing staff as dismissive of difficulties. Comparisons between DF and cancer were commonly discussed. Some participants felt relieved that they did not have cancer; others perceived that their needs were secondary to cancer patients and believed they were treated as less important. Participants discussed negative impact of DF on psychosocial well-being. Chronic pain and activity limitations seemed to impact mood and relationships. Conclusion. Greater awareness and understanding of DF by health professionals may help to reduce diagnostic delay and improve support. Individuals may benefit from being treated by specialist DF teams.
Supplemental Figure S6 from Expressed Barcoding Enables High-Resolution Tracking of the Evolution of Drug Tolerance
Authors: Cotton Jennifer L. , Estrada Diez Javier , Sagar Vivek , Chen Julie , Piquet Michelle , Alford John , Song Youngchul , Li Xiaoyan , Riester Markus , DiMare Matthew T. , Schumacher Katja , Boulay Gaylor , Sprouffske Kathleen , Fan Lin , Burks Tyler , Mansur Leandra , Wagner Joel , Bhang Hyo-eun C. , Iartchouk Oleg , Reece-Hoyes John , Morris Erick J. , Hammerman Peter S. , Ruddy David A. , Korn Joshua M. , Engelman Jeffrey A. , Niederst Matthew J.
Published: November 2023

Supplemental Figure S6 shows clone family UMAPs, proportion change in response to drug, and gene signature set expression at untreated and acute drug treatment.
Supplemental Figure S5 from Expressed Barcoding Enables High-Resolution Tracking of the Evolution of Drug Tolerance
Authors: Cotton Jennifer L. , Estrada Diez Javier , Sagar Vivek , Chen Julie , Piquet Michelle , Alford John , Song Youngchul , Li Xiaoyan , Riester Markus , DiMare Matthew T. , Schumacher Katja , Boulay Gaylor , Sprouffske Kathleen , Fan Lin , Burks Tyler , Mansur Leandra , Wagner Joel , Bhang Hyo-eun C. , Iartchouk Oleg , Reece-Hoyes John , Morris Erick J. , Hammerman Peter S. , Ruddy David A. , Korn Joshua M. , Engelman Jeffrey A. , Niederst Matthew J.
Published: November 2023

Supplemental Figure S5 shows distribution of barcoded clones into Louvain clusters.
Figure S4 from Matrix Stiffness Triggers Lipid Metabolic Cross-talk between Tumor and Stromal Cells to Mediate Bevacizumab Resistance in Colorectal Cancer Liver Metastases
Authors: Zheng Yannan , Zhou Rui , Cai Jianan , Yang Nanyan , Wen Zhaowei , Zhang Zhihua , Sun Huiying , Huang Genjie , Guan Yijin , Huang Na , Shi Min , Liao Yulin , Bin Jianping , Liao Wangjun
Published: November 2023

Figure. S4 High stiffness-induced HSCs promote FAO metabolism in colon cancer cells through secreting FFAs.
Supplementary tables from DNA Methylation-Based Testing in Peripheral Blood Mononuclear Cells Enables Accurate and Early Detection of Colorectal Cancer
Authors: Xie Yan , Li Peilong , Sun Dong , Qi Qiuchen , Ma Suhong , Zhao Yinghui , Zhang Shujun , Wang Tiantian , Wang Jing , Li Shijun , Gong Tingting , Xu Huiting , Xiong Mengqiu , Li Guanghua , You Chongge , Luo Zhaofan , Li Juan , Wang Chuanxin , Du Lutao
Published: November 2023

Supplementary tables
Figure S4 from Cross-talk between Myeloid and B Cells Shapes the Distinct Microenvironments of Primary and Secondary Liver Cancer
Authors: Chen Zhihang , Zhang Guopei , Ren Xiaoxue , Yao Zhijia , Zhou Qian , Ren Xuxin , Chen Shuling , Xu Lixia , Sun Kaiyu , Zeng Qianwen , Kuang Ming , Kuang Dong-Ming , Peng Sui
Published: November 2023

Figure S4
Data from Matrix Stiffness Triggers Lipid Metabolic Cross-talk between Tumor and Stromal Cells to Mediate Bevacizumab Resistance in Colorectal Cancer Liver Metastases
Authors: Zheng Yannan , Zhou Rui , Cai Jianan , Yang Nanyan , Wen Zhaowei , Zhang Zhihua , Sun Huiying , Huang Genjie , Guan Yijin , Huang Na , Shi Min , Liao Yulin , Bin Jianping , Liao Wangjun
Published: November 2023

Abstract
Bevacizumab is an anti-VEGF monoclonal antibody that plays an important role in the combination treatment of advanced colorectal cancer. However, resistance remains a major hurdle limiting bevacizumab efficacy, highlighting the importance of identifying a mechanism of antiangiogenic therapy resistance. Here, we investigated biophysical properties of the extracellular matrix (ECM) related to metabolic processes and acquired resistance to bevacizumab. Evaluation of paired pre- and posttreatment samples of liver metastases from 20 colorectal cancer patients treated with combination bevacizumab therapy, including 10 responders and 10 nonresponders, indicated that ECM deposition in liver metastases and a highly activated fatty acid oxidation (FAO) pathway were elevated in nonresponders after antiangiogenic therapy compared with responders. In mouse models of liver metastatic colorectal cancer (mCRC), anti-VEGF increased ECM deposition and FAO in colorectal cancer cells, and treatment with the FAO inhibitor etomoxir enhanced the efficacy of antiangiogenic therapy. Hepatic stellate cells (HSC) were essential for matrix stiffness–mediated FAO in colon cancer cells. Matrix stiffness activated lipolysis in HSCs via the focal adhesion kinase (FAK)/yes-associated protein (YAP) pathway, and free fatty acids secreted by HSCs were absorbed as metabolic substrates and activated FAO in colon cancer cells. Suppressing HSC lipolysis using FAK and YAP inhibition enhanced the efficacy of anti-VEGF therapy. Together, these results indicate that bevacizumab-induced ECM remodeling triggers lipid metabolic cross-talk between colon cancer cells and HSCs. This metabolic mechanism of bevacizumab resistance mediated by the physical tumor microenvironment represents a potential therapeutic target for reversing drug resistance.
Significance:
Extracellular matrix stiffening drives bevacizumab resistance by stimulating hepatic stellate cells to provide fuel for mCRC cells in the liver, indicating a potential metabolism-based therapeutic strategy for overcoming resistance.
Supplementary Figure S9 from Clinical and Molecular Features of Long-term Response to Immune Checkpoint Inhibitors in Patients with Advanced Non–Small Cell Lung Cancer
Authors: Thummalapalli Rohit , Ricciuti Biagio , Bandlamudi Chaitanya , Muldoon Daniel , Rizvi Hira , Elkrief Arielle , Luo Jia , Alessi Joao V. , Pecci Federica , Lamberti Giuseppe , Di Federico Alessandro , Hong Lingzhi , Zhang Jianjun , Heymach John V. , Gibbons Don L. , Plodkowski Andrew J. , Ravichandran Vignesh , Donoghue Mark T.A. , Vanderbilt Chad , Ladanyi Marc , Rudin Charles M. , Kris Mark G. , Riely Gregory J. , Chaft Jamie E. , Hellmann Matthew D. , Vokes Natalie I. , Awad Mark M. , Schoenfeld Adam J.
Published: November 2023

Frequency of long-term response (LTR) and short-term response (STR) according to composite PD-L1 and tumor mutational burden (TMB) status.
Supplementary Figure S6 from SPOP Mutations Target STING1 Signaling in Prostate Cancer and Create Therapeutic Vulnerabilities to PARP Inhibitor–Induced Growth Suppression
Authors: Geng Chuandong , Zhang Man-Chao , Manyam Ganiraju C. , Vykoukal Jody V. , Fahrmann Johannes F. , Peng Shan , Wu Cheng , Park Sanghee , Kondraganti Shakuntala , Wang Daoqi , Robinson Brian D. , Loda Massimo , Barbieri Christopher E. , Yap Timothy A. , Corn Paul G. , Hanash Samir , Broom Bradley M. , Pilié Patrick G. , Thompson Timothy C.
Published: November 2023

Supplementary Fig. S6. Far western blotting assay to detect direct protein-protein interaction of SPOP and STING protein in vitro
Supplementary Figure S20 from SPOP Mutations Target STING1 Signaling in Prostate Cancer and Create Therapeutic Vulnerabilities to PARP Inhibitor–Induced Growth Suppression
Authors: Geng Chuandong , Zhang Man-Chao , Manyam Ganiraju C. , Vykoukal Jody V. , Fahrmann Johannes F. , Peng Shan , Wu Cheng , Park Sanghee , Kondraganti Shakuntala , Wang Daoqi , Robinson Brian D. , Loda Massimo , Barbieri Christopher E. , Yap Timothy A. , Corn Paul G. , Hanash Samir , Broom Bradley M. , Pilié Patrick G. , Thompson Timothy C.
Published: November 2023

Supplementary Fig. S20. Immunofluorescence staining analysis of PARP1 in C4-2b-empty vector and C4-2b-SPOPF133V xenograft tumors treated with talazoparib (TALA) or control vehicle
Supplementary Figure S19 from SPOP Mutations Target STING1 Signaling in Prostate Cancer and Create Therapeutic Vulnerabilities to PARP Inhibitor–Induced Growth Suppression
Authors: Geng Chuandong , Zhang Man-Chao , Manyam Ganiraju C. , Vykoukal Jody V. , Fahrmann Johannes F. , Peng Shan , Wu Cheng , Park Sanghee , Kondraganti Shakuntala , Wang Daoqi , Robinson Brian D. , Loda Massimo , Barbieri Christopher E. , Yap Timothy A. , Corn Paul G. , Hanash Samir , Broom Bradley M. , Pilié Patrick G. , Thompson Timothy C.
Published: November 2023

Supplementary Fig. S19. Heatmaps of common differentially expressed genes in co-cultured and mono-cultured prostate cancer model tumor cells demonstrating significant (FDR < 0.05) interaction between treatment [OLA or vehicle control (DMSO)] and SPOP phenotype (RM-1-BM-SPOPF133V mutant–expressing prostate cancer cells w/ or w/o RAW264.7 macrophage cocultured).
Supplementary Figure S17 from SPOP Mutations Target STING1 Signaling in Prostate Cancer and Create Therapeutic Vulnerabilities to PARP Inhibitor–Induced Growth Suppression
Authors: Geng Chuandong , Zhang Man-Chao , Manyam Ganiraju C. , Vykoukal Jody V. , Fahrmann Johannes F. , Peng Shan , Wu Cheng , Park Sanghee , Kondraganti Shakuntala , Wang Daoqi , Robinson Brian D. , Loda Massimo , Barbieri Christopher E. , Yap Timothy A. , Corn Paul G. , Hanash Samir , Broom Bradley M. , Pilié Patrick G. , Thompson Timothy C.
Published: November 2023

Supplementary Fig. S17. Original unedited IB images for representative Western blots experiments (n-2) used in Figure 4E right panels (RM-1-BM-EV/ SPOPmuts).
Data from Preclinical Development of Brain Permeable ERβ Agonist for the Treatment of Glioblastoma
Authors: Pratap Uday P. , Tidwell Michael , Balinda Henriette U. , Clanton Nicholas A. , Yang Xue , Viswanadhapalli Suryavathi , Sareddy Gangadhara R. , Liang Dong , Xie Huan , Chen Yidong , Lai Zhao , Tekmal Rajeshwar R. , McHardy Stanton F. , Brenner Andrew J. , Vadlamudi Ratna K.
Published: November 2023

Abstract
Glioblastoma (GBM) is the most prevalent and aggressive type of adult brain tumors with low 5-year overall survival rates. Epidemiologic data suggest that estrogen may decrease brain tumor growth, and estrogen receptor beta (ERβ) has been demonstrated to exert antitumor functions in GBM. The lack of potent, selective, and brain permeable ERβ agonist to promote its antitumor action is limiting the therapeutic promise of ERβ. In this study, we discovered that Indanone and tetralone-keto or hydroxyl oximes are a new class of ERβ agonists. Because of its high activity in ERβ reporter assays, specific binding to ERβ in polar screen assays, and potent growth inhibitory activity in GBM cells, CIDD-0149897 was discovered as a possible hit by screening a library of compounds. CIDD-0149897 is more selective for ERβ than ERα (40-fold). Treatment with CIDD-0149897 markedly reduced GBM cell viability with an IC50 of ∼7 to 15 μmol/L, while having little to no effect on ERβ-KO cells and normal human astrocytes. Further, CIDD-0149897 treatment enhanced expression of known ERβ target genes and promoted apoptosis in established and patient-derived GSC models. Pharmacokinetic studies confirmed that CIDD-0149897 has systemic exposure, and good bioavailability in the brain. Mice tolerated daily intraperitoneal treatment of CIDD-0149897 (50 mg/kg) with a 7-day repeat dosage with no toxicity. In addition, CIDD-0149897 treatment significantly decreased tumor growth in U251 xenograft model and extended the survival of orthotopic GBM tumor-bearing mice. Collectively, these findings pointed to CIDD-0149897 as a new class of ERβ agonist, offering patients with GBM a potential means of improving survival.
Data from A Novel Role of Prostate-Specific Membrane Antigen in Telomere Stability in Prostate Cancer Cells
Authors: Reddy Vidyavathi , Hwang Clara , Reddy G. Prem-Veer , Kim Sahn-Ho
Published: November 2023

Abstract
Prostate-specific membrane antigen (PSMA) expression increases with prostate cancer grade and progression; however, the role of PSMA in prostate cancer progression remains poorly understood. Telomere stability is essential for the survival and genome stability of cancer cells. We found massive telomere DNA damage in PSMA-negative prostate cancer cells (PC-3 and DU145) compared with PSMA-positive prostate cancer (LNCaP) cells. The ectopic expression of PSMA suppressed telomere DNA damage in PC3 cells. PSMA inhibitor, 2-PMPA, and PSMA knockdown induced telomere DNA damage in PSMA-positive LNCaP cells but not in PSMA-negative PC-3 cells, suggesting that PSMA plays a critical role in telomere stability in prostate cancer cells. In addition, we observed that inhibition of PSMA or inhibition of glutamate receptor, which mediates PSMA-dependent activation of AKT, suppressed AKT phosphorylation, and caused telomere DNA damage. Furthermore, 2-PMPA-induced telomere DNA damage in LNCaP cells was associated with telomere aberrations, such as telomere–telomere fusions, sister–chromatid telomere fusions, and telomere breakages. AKT is reported to promote cell growth by stabilizing telomere association with telomere-binding proteins TRF1 and TPP1. We observed that TRF1 and TPP1 transfection of LNCaP cells attenuated the inhibitory effect of 2-PMPA on cell growth and telomere DNA damage. Together, these observations indicate that PSMA role in maintaining telomere stability in prostate cancer cells is mediated by AKT. Thus, these studies reveal an important role of PSMA in maintaining telomere stability that can promote cell survival and, thereby, prostate cancer progression.
Implications:
Role of PSMA in telomere stability suggests a strong correlation between PSMA expression and prostate cancer progression.
Data from Exon junction complex mediates the cap-independent translation of circular RNA
Authors: Lin Hui-Hsuan , Chang Chiu-Yuan , Huang Yi-Ren , Shen Che-Hung , Wu Yu-Chen , Chang Kai-Li , Lee Yueh-Chun , Lin Ya-Chi , Ting Wen-Chien , Chien Han-Ju , Zheng Yi-Feng , Lai Chien-Chen , Hsiao Kuei-Yang
Published: November 2023

Abstract
Evidence that circular RNAs (circRNAs) serve as protein template is accumulating. However, how the cap-independent translation is controlled remains largely uncharacterized. Here we show that the presence of intron and thus splicing promote cap-independent translation. By acquiring the exon junction complex (EJC) after splicing, the interaction between circRNA and ribosomes was promoted, thereby facilitating translation. Prevention of splicing by treatment with spliceosome inhibitor or mutating splicing signal hindered cap-independent translation of circRNA. Moreover, EJC-tethering using Cas13 technology reconstituted EJC-dependent circRNA translation. Finally, the level of a coding circRNA from succinate dehydrogenase assembly factor 2 (circSDHAF2) was found to be elevated in the tumorous tissues from patients with colorectal cancer (CRC) and shown to be critical in tumorigenesis of CRC in both cell and murine models. These findings reveal that EJC-dependent control of circSDHAF2 translation is involved in the regulation of oncogenic pathways.
Implications: EJC-mediated cap-independent translation of circRNA is implicated in the tumorigenesis of colorectal cancer.
Paracentral Acute Middle Maculopathy in Migraines with Aura
Authors: Milad Daniel , Antaki Fares , Farah Andrew , Hammamji Karim , Saab Marc
Published: November 2023

Paracentral acute middle maculopathy (PAMM) has recently been described following episodes of migraine. In this report, we present a case of PAMM and describe the role of en face optical coherence tomography (OCT). A 75-year-old woman presented with subjective vision loss over a 2-week period in the right eye. She was known for migraines with aura that presented with progressive spreading of positive and negative visual phenomena which usually resolved in under an hour. Her recent migraine episode was “atypical,” as it lasted 3 days. She also experienced a monocular central scotoma with “black spots and jagged, zig-zag edges.” The positive auras resolved spontaneously, whereas the central scotoma persisted. Spectral domain OCT showed an area of perifoveal hyperreflectivity from the inner plexiform to the outer plexiform layers consistent with PAMM. The mid-retina en face OCT and OCT angiography demonstrated an ovoid focal patch of hyperreflectivity with flow interruption, characteristic of globular PAMM. We diagnosed her with migraines with aura and presumed retinal vasospasm, complicated by retinal ischemia in the form of globular PAMM. Acute retinal ischemia, which may require urgent neurovascular workup and giant cell arteritis evaluation, must be considered in patients with migraines alongside persistent visual changes. Diagnosing PAMM requires a high level of suspicion since it can present without significant changes in visual acuity, visual fields, and fundus photographs. With the inclusion of en face OCT in the clinicians’ diagnostic armamentarium, the slightest signs of retinal ischemic changes, such as PAMM, become evident.
Solidariedade atlântica: Movimento Afro-Brasileiro Pró-Libertação de Angola (MABLA), entre percursos e conexões
Authors: Lima Viviane de Souza
Published: November 2023

Este artigo se propõe a evidenciar como o movimento brasileiro em apoio às independências africanas, criado na década de 1960, conseguiu formatar uma rede de solidariedade aos movimentos nacionalistas africanos, principalmente, o MPLA, e dar maior visibilidade à luta de independência nas colônias portuguesas, principalmente em Angola. O Movimento Afro-Brasileiro Pró-Libertação de Angola (MABLA) reuniu brasileiros, africanos e portugueses antissalazaristas e atuou, principalmente, nas cidades de São Paulo e do Rio de Janeiro. O MABLA foi um movimento de configuração móvel que reuniu apoiadores de diversas tendências ideológicas em torno de um projeto comum: a defesa da independência dos povos africanos.
Telehealth and Health Equity in Older Adults With Heart Failure: A Scientific Statement From the American Heart Association
Authors: Masterson Creber Ruth , Dodson John A. , Bidwell Julie , Breathett Khadijah , Lyles Courtney , Harmon Still Carolyn , Ooi Sze-Yuan , Yancy Clyde , Kitsiou Spyros ,   on behalf of the American Heart Association Cardiovascular Disease in Older Populations Committee of the Council on Clinical Cardiology and the Council on Cardiovascular and Stroke Nursing; Council on Quality of Care and Outcomes Research; and Council on Peripheral Vascular Disease
Published: November 2023

Enhancing access to care using telehealth is a priority for improving outcomes among older adults with heart failure, increasing quality of care, and decreasing costs. Telehealth has the potential to increase access to care for patients who live in underresourced geographic regions, have physical disabilities or poor access to transportation, and may not otherwise have access to cardiologists with expertise in heart failure. During the COVID-19 pandemic, access to telehealth expanded, and yet barriers to access, including broadband inequality, low digital literacy, and structural barriers, prevented many of the disadvantaged patients from getting equitable access. Using a health equity lens, this scientific statement reviews the literature on telehealth for older adults with heart failure; provides an overview of structural, organizational, and personal barriers to telehealth; and presents novel interventions that pair telemedicine with in-person services to mitigate existing barriers and structural inequities.
Brain signal variability and executive functions across the life span
Authors: Goodman Zachary T. , Nomi Jason S. , Kornfeld Salome , Bolt Taylor , Saumure Roger A. , Romero Celia , Bainter Sierra A. , Uddin Lucina Q.
Published: November 2023

Neural variability is thought to facilitate survival through flexible adaptation to changing environmental demands. In humans, such capacity for flexible adaptation may manifest as fluid reasoning, inhibition of automatic responses, and mental set-switching—skills falling under the broad domain of executive functions that fluctuate over the life span. Neural variability can be quantified via the BOLD signal in resting-state fMRI. Variability of large-scale brain networks is posited to underpin complex cognitive activities requiring interactions between multiple brain regions. Few studies have examined the extent to which network-level brain signal variability across the life span maps onto high-level processes under the umbrella of executive functions. The present study leveraged a large publicly available neuroimaging dataset to investigate the relationship between signal variability and executive functions across the life span. Associations between brain signal variability and executive functions shifted as a function of age. Limbic-specific variability was consistently associated with greater performance across subcomponents of executive functions. Associations between executive function subcomponents and network-level variability of the default mode and central executive networks, as well as whole-brain variability, varied across the life span. Findings suggest that brain signal variability may help to explain to age-related differences in executive functions across the life span.
Mouthparts of the crab Goniopsis cruentata (Latreille, 1803) (Decapoda, Brachyura, Grapsidae): morphological variations associated with environment, sex and stage of development
Authors: Soares-Silva Ana Carla , da Conceição Guerreiro Couto Erminda , Carvalho Fabrício Lopes
Published: November 2023

Individuals and populations can display variations in distinct aspects of their life histories, which could be reflected in their morphological characteristics. This study analyzed the mouthpart morphology of the crab Goniopsis cruentata in relation to environment, sex and stage of development. Our results indicate differences in the number of setae between developmental stages and environments, as well as the interaction between developmental stages and environments. There were no differences in setae types between stages, sexes or environments. There were differences in the shape of the ischium between adults and juveniles, with a more homogeneous ischium in juveniles than adults. We also found differences in food content between developmental stages, as well as an interaction between developmental stages and environment. Our results support an association between diet and morphology of mouthparts in G. cruentata, and that these apparatuses vary according to ontogenetic development and the environmental conditions that species are exposed to. These associations should be considered in studies that use these characteristics to verify morphological responses to environmental variations.
Astragalus pseudoanisacanthus, a new species of section Poterion from northern Balochistan (Pakistan)
Authors: KHAN AMJAD , SULTAN AMIR , ZARRE SHAHIN , ISHAQ KAMRAN
Published: November 2023

Astragalus pseudoanisacanthus, a new species from northern Balochistan (Pakistan), is described and illustrated. The new species is a perennial, loosely branched, slender spiny shrub characterized by whitish corolla and broadly ellipsoid standard limb. The legume is semi-bilocular, 2‒4-seeded and sparsely pilose with white hairs. The morphological, anatomical, pollen and seed morphological features of A. pseudoanisacanthus are compared with its closely related species, i.e. A. anisacanthus.
Observations of Boundary Layer Convergence Lines and Associated Updrafts in the U.S. Southern Great Plains
Authors: Liu Shanhe , Sindhu Kapil D. , Kirshbaum Daniel J.
Published: November 2023

Boundary layer convergence lines (CLs) are highly effective at deep-convection initiation (DCI), suggesting that their associated updraft properties differ from those of more widespread turbulent updrafts in the planetary boundary layer (PBL). This study exploits observations at the Atmospheric Radiation Measurement Southern Great Plains (ARM SGP) observatory in Oklahoma from 2011 to 2016 to quantify CL properties and their relation to turbulent PBL eddies preceding CL arrival. Two independent methods for estimating CL properties are developed at two locations in the SGP region, both relying on the assumption of a 2D circulation in the CL-normal plane but using different combinations of instruments. The first (the radar method) relies mainly on scanning radar data and is applied to 61 CLs passing near a high-resolution scanning radar based in Nardin, Oklahoma, while the second (the surface method) relies mainly on surface wind data and is applied to 68 CLs crossing the SGP facility in nearby Lamont, Oklahoma. Mean daytime (1000–1900 LST) CL width (∼2 km) and convergence magnitude (∼0.003 s−1) are similar for both methods, and mean daytime CL depth is ∼0.75 km. The two methods disagree at night (0000–1000 and 1900–2400 LST), where the surface method estimates wider and weaker CLs than the radar method. This difference may stem from the radar beam overshooting the shallow, highly stable nocturnal PBL. The largest CL updrafts are slightly wider (∼20%) and stronger (∼40%) than the largest PBL updrafts in the pre-CL period, generating 50%–100% larger updraft mass fluxes over most of the PBL depth.

Significance Statement

Deep convection is commonly initiated by boundary layer convergence lines (CLs), which are associated with intense surface-based wind convergence and strong updrafts that may lift air to saturation. Although CLs form regularly, they are far less common than ordinary, short-lived turbulent thermals in the daytime boundary layer. To better understand why CLs are so effective at deep-convection initiation, we observationally quantify their morphologies and strengths and compare these properties to those of surrounding turbulent updrafts. Perhaps surprisingly, the CLs are found to exhibit only slightly larger scales and strengths as the turbulent updrafts. Although these marginal increases help to explain the preference for storms to initiate along CLs, they likely are not the whole story.