bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identifying potential targets for lung cancer intervention by analyzing the crosstalk of cancer‐associated fibroblasts and immune and metabolism microenvironment
Authors: Wei Shiyou , Bao Minwei , Zhu Yuming , Zhang Wentian , Jiang Lei 
Published: April 2023

AbstractBackgroundCancer‐associated fibroblasts (CAFs) have been reported to play a crucial role in the tumor microenvironment and progression.MethodsThe data used in this study were obtained from the Cancer Genome Atlas and Gene Expression Omnibus databases, and all analyses were performed using R software.ResultsWe first quantified the CAFs infiltration through single sample gene set enrichment analysis in the TCGA and combined GEO cohort (GSE30219, GSE37745, and GSE50081). Our result showed that patients with high levels of CAF infiltration were associated with worse clinical features and poor prognosis. Immune microenvironment analysis indicated that high CAF infiltration might result in increased infiltration of immune cells, including aDC, B cells, CD8+ T cells, cytotoxic cells, DC, eosinophils, iDC, macrophages, mast cells, neutrophils, NK CD56dim cells, NK cells, pDC, and T cells. Correlation analysis showed a significant positive correlation between CAFs and M2 macrophages, while a negative correlation was found between CAFs and glycerophospholipid metabolism. Kaplan‐Meier survival curves indicated that glycerophospholipid metabolism was a protective factor against lung cancer. Biological enrichment analysis showed that pathways such as allograft rejection, epithelial–mesenchymal transition, KRAS signaling, TNF‐α signaling, myogenesis, IL6/JAK/STAT3 signaling, IL2/STAT5 signaling were upregulated in the patients with high CAF infiltration. Moreover, patients with high CAF infiltration had a lower proportion of immunotherapy responders. Genome analysis showed that low CAFs infiltration was associated with high genome instability. We identified FGF5 and CELF3 as key genes involved in the interaction between CAFs, M2 macrophages, and glycerophospholipid metabolism, and further analyzed FGF5. In vitro experiments showed that FGF5 promoted the proliferation, invasion and migration of lung cancer cells and was primarily localized in the nucleoli fibrillar center.ConclusionsOur study provides novel insights into the roles of CAFs in lung cancer progression and the underlying crosstalk of tumor metabolism and immune microenvironment.
EPN3 plays oncogenic role in non‐small cell lung cancer by activating the JAK1/2‐STAT3 pathway
Authors: Meng Jiguang , Zhang Chunyang , Zhu Nengyang , Zhang Caiyun , Liu Meng , Han Zhihai , Li Yongqun 
Published: April 2023

AbstractThe effect of Epsin 3 (EPN3) on non‐small cell lung cancer (NSCLC) has not yet been clearly elucidated. This study identified the exact function of EPN3 on NSCLC progression. EPN3 expression in NSCLC patients were analyzed based on the Cancer Genome Atlas database. Kaplan–Meier analysis was implemented to research the effect of EPN3 on patients' survival. EPN3 expression in clinical tissues of 62 NSCLC cases was monitored by real‐time quantitative reverse transcription polymerase chain reaction, immunohistochemistry and Western blot. A549 and H1299 cells were transfected with EPN3 shRNA and treated by RO8191 (20 μM). Proliferation was researched by cell counting kit‐8 and 5‐ethnyl‐2 deoxyuridine assays. Apoptosis was monitored by flow cytometry. Migration and invasion was assessed by Transwell experiment. EPN3 effect on A549 cell in vivo growth was researched using nude mice. RO8191 (200 μg) was intratumoral injected into mice. Immunohistochemistry and Western blot was implemented to monitor protein expression in cells and xenograft tumor tissues. EPN3 was abnormally up‐regulated in NSCLC patients and cells, indicating a lower overall survival. Loss of EPN3 weakened proliferation, migration and invasion, induced apoptosis, and repressed epithelial‐mesenchymal transition in NSCLC cells. Loss of EPN3 inactivated the JAK1/2‐STAT3 pathway in NSCLC cells. RO8191 treatment reversed the inhibition of EPN3 knockdown on the malignant phenotype of NSCLC cells. RO8191 intratumoral injection reversed the suppression of EPN3 silencing on NSCLC cell in vivo growth. EPN3 acted as an oncogene in NSCLC via activating the JAK1/2‐STAT3 pathway. EPN3 may be a promising target for NSCLC treatment.
Histaminergic neurotransmission in aging and Alzheimer's disease: A review of therapeutic opportunities and gaps
Authors: Satpati Abhijit , Neylan Thomas , Grinberg Lea T. 
Published: April 2023

AbstractIntroductionAlzheimer's disease (AD) is a progressive neurodegenerative disorderfeaturing a brain accumulation of extracellular β‐amyloidplaques (Aβ) and intracellular neurofibrillary tautangles (NFTs). Although cognitive decline is a disease‐defining symptom of AD, sleep dysfunction, a common symptom often preceding cognitive decline, hasrecently gained more attention as a core AD symptom. Polysomnography and othersleep measures show sleep fragmentation with shortening of N3 sleep togetherwith excessive daytime sleepiness (EDS) and sundowning as the main findings in AD patients. The latter reflects dysfunction of the wake‐promoting neurons (WPNs), including histaminergic neurons (HAN) located in thetuberomammillary nucleus (TMN) of the posterior hypothalamus, which projectunmyelinated axons to various parts of the brain. Histamine's role in cognitionand arousal is broadly recognized. Selective targeting of histaminergic subtype‐3 and 4 receptors show therapeutic potential in rodent models of AD andaging.MethodBased on PubMed, Scopus, and google scholar databases search, this review summarizes the current knowledge on the histaminergic system in AD and aging, its therapeutic potential in AD, and highlight areas where moreresearch is needed.ResultsAnimal studies have demonstrated that pharmacological manipulation of histaminergic receptors or histamine supplementation improves cognition in AD models. However, measurements of HA or HA metabolite levels in the human brainand CSF present contradictory reports due to either lack of power or controls for known confounders.DiscussionSystemic studies including broad age, sex, neuropathological diagnosis, and disease stage are warranted to fill the gap in our current understanding of the histaminergic neurotransmitter/neuromodulator system in humans, especially age‐related changes, and therapeuticpotential of histamine in AD‐related dysfunction.
Multi‐ligand functionalized blood‐to‐tumor sequential targeting strategies in the field of glioblastoma nanomedicine
Authors: Martins Cláudia , Sarmento Bruno 
Published: April 2023

AbstractGlioblastoma (GBM) is an unmet clinical need characterized by a standard of care (SOC) 5‐year survival rate of only 5%, and a treatment mostly palliative. Significant hurdles in GBM therapies include an effective penetration of therapeutics through the brain protective barrier, namely the blood–brain barrier (BBB), and a successful therapeutic delivery to brain‐invading tumor cells post‐BBB crossing. These hurdles, along with the poor prognosis and critical heterogeneity of the disease, have shifted attention to treatment modalities with capacity to precisely and sequentially target (i) BBB cells, inducing blood‐to‐brain transport, and (ii) GBM cells, leading to a higher therapeutic accumulation at the tumor site. This sequential targeting allows therapeutic molecules to reach the brain parenchyma and compromise molecular processes that support tumor cell invasion. Besides improving formulation and pharmacokinetics constraints of drugs, nanomedicines offer the possibility of being surface functionalized with multiple possibilities of targeting ligands, while delivering the desired therapeutic cargos to the biological sites of interest. Targeting ligands exploit the site‐specific expression or overexpression of specific molecules on BBB and GBM cells, triggering brain plus tumor transport. Since the efficacy of single‐ligand functionalized nanomedicines is limited due to the GBM anatomical site (brain) and disease complexity, this review presents an overview of multi‐ligand functionalized, BBB and GBM sequentially‐ and dual‐targeted nanomedicines reported in literature over the last 10 years. The role of the BBB in GBM progression, treatment options, and the multiple possibilities of currently available targeting ligands will be summarized.This article is categorized under:
Nanotechnology Approaches to Biology > Nanoscale Systems in Biology
Therapeutic Approaches and Drug Discovery > Nanomedicine for Oncologic Disease
Scenario-Based Foresight in the Age of Digital Technologies and AI
Authors: Ködding Patrick , Koldewey Christian , Dumitrescu Roman 
Published: April 2023

AbstractScenario-based foresight is used less and less in the corporate world despite continued high satisfaction with the obtained results. In the age of digitalization, many companies feel increasingly forced to short-termism instead of strategic planning. However, emerging digital technologies, such as artificial intelligence (AI), represent a promising approach to cope with the traditional challenges of scenario-based foresight as well as new challenges added by digitalization. Therefore, this work-in-progress paper identifies and analyzes use cases for scenario-based foresight with digital technologies employing a systematic analysis of the relevant literature.In the paper at hand, we show that the use of digital technologies for improving the performance of scenario-based foresight is an emerging field. We identify 14 so-called use cases, i.e., unique goal-oriented applications of digital technologies for scenario-based foresight. In general, the use cases show that currently digital technologies can enhance, not substitute the capabilities of scenario-based foresight practitioners. Digital technologies primarily support the analysis of large amounts of data, e.g., for collecting futuristic data and identifying key influence factors. However, activities that require implicit knowledge and creativity, like the interpretation of scenarios, are currently still left to humans.
Collaborative Work Enabled by Immersive Environments
Authors: Mayer Anjela , Chardonnet Jean-Rémy , Häfner Polina , Ovtcharova Jivka 
Published: April 2023

AbstractDigital transformation facilitates new methods for remote collaboration while shaping a new understanding of working together. In this chapter, we consider global collaboration in the context of digital transformation, discuss the role of Collaborative Virtual Environments (CVEs) within the transformation process, present an overview of the state of CVEs and go into more detail on significant challenges in CVEs by providing recent approaches from research.
Jet-veto resummation at N3LLp + NNLO in boson production processes
Authors: Campbell John M. , Ellis R. Keith , Neumann Tobias , Seth Satyajit 
Published: April 2023

Abstract
Vetoing energetic jet activity is a crucial tool for suppressing backgrounds and enabling new physics searches at the LHC, but the introduction of a veto scale can introduce large logarithms that may need to be resummed. We present an implementation of jet-veto resummation for color-singlet processes at the level of N3LLp matched to fixed-order NNLO predictions. Our public code MCFM allows for predictions of a single boson, such as Z/γ*, W± or H, or with a pair of vector bosons, such as W+W−, W±Z or ZZ. The implementation relies on recent calculations of the soft and beam functions in the presence of a jet veto over all rapidities, with jets defined using a sequential recombination algorithm with jet radius R. However one of the ingredients that is required to reach full N3LL accuracy is only known approximately, hence N3LLp. We describe in detail our formalism and compare with previous public codes that operate at the level of NNLL. Our higher-order predictions improve significantly upon NNLL calculations by reducing theoretical uncertainties. We demonstrate this by comparing our predictions with ATLAS and CMS results.
Phase diagram of holographic thermal dense QCD matter with rotation
Authors: Zhao Yan-Qing , He Song , Hou Defu , Li Li , Li Zhibin 
Published: April 2023

Abstract
We study the rotation effects of the hot and dense QCD matter in a non-perturbative regime by the gauge/gravity duality. We use the gravitational model that is designated to match the state-of-the-art lattice data on the thermal properties of (2+1)-flavor QCD and predict the location of the critical endpoint and the first-order phase transition line at large baryon chemical potential without rotation. After introducing the angular velocity via a local Lorentz boost, we investigate the thermodynamic quantities for the system under rotation in a self-consistent way. We find that the critical temperature and baryon chemical potential associated with the QCD phase transition decrease as the angular velocity increases. Moreover, some interesting phenomena are observed near the critical endpoint. We then construct the 3-dimensional phase diagram of the QCD matter in terms of temperature, baryon chemical potential, and angular velocity. As a parallel investigation, we also consider the gravitational model of SU(3) pure gluon system, for which the 2-dimensional phase diagram associated with temperature and angular velocity has been predicted. The corresponding thermodynamic quantities with rotation are investigated.
Maximal Operators, Littlewood–Paley Functions and Variation Operators Associated with Nonsymmetric Ornstein–Uhlenbeck Operators
Authors: Almeida Víctor , Betancor Jorge J. , Quijano Pablo , Rodríguez-Mesa Lourdes 
Published: April 2023

AbstractIn this paper, we establish $$L^p$$

L
p

boundedness properties for maximal operators, Littlewood–Paley functions and variation operators involving Poisson semigroups and resolvent operators associated with nonsymmetric Ornstein–Uhlenbeck operators. We consider the Ornstein–Uhlenbeck operators defined by the identity as the covariance matrix and having a drift given by the matrix $$-\lambda (I+R)$$

-
λ
(
I
+
R
)

, being $$\lambda >0$$

λ
>
0

and R a skew-adjoint matrix. The semigroups associated with these Ornstein–Uhlenbeck operators are the basic building blocks of all the normal Ornstein–Uhlenbeck semigroups.
The impact of sodomy law repeals on crime
Authors: Ciacci Riccardo , Sansone Dario 
Published: April 2023

AbstractWe exploit variations in the timing of decriminalization of same-sex sexual intercourse across US states to estimate the impact of these law changes on crime through difference-in-differences and event study models. We provide the first evidence that sodomy law repeals led to a decline in the number of arrests for disorderly conduct, prostitution, and other sex offenses. Moreover, in line with the hypothesis that sodomy law repeals enhanced mental health and lessened minority stress, we show that these repeals led to a reduction in arrests for drug and alcohol consumption.
Age-related effects of repeated task switching in a novel voluntary gait adaptability task
Authors: Kim Kyungwan , Deller Lena , Vinent Marie , Zijlstra Wiebren 
Published: April 2023

AbstractAge-related effects of task switching have been extensively studied based on cognitive tasks and simple motor tasks, but less on complex cognitive-motor tasks involving dynamic balance control while walking. The latter tasks may especially be difficult and relevant for older adults in terms of safe mobility in daily life. The aim of the present study was, therefore, to examine age-related changes in task-switching adaptability using a novel voluntary gait adaptability test protocol. Fifteen healthy young (27.5 ± 2.9 years) and 16 healthy old (70.9 ± 7.6 years) adults carried out 2 different visual target stepping tasks (either target avoidance or stepping) twice in a block (A–B–A–B, 2 min per task; three blocks in total) without any intrablock breaks. Our results showed that old adults showed significantly more step errors both in Tasks A and B as well as more interference effects than young adults. Age-related differences in step accuracy were significant in the anterior–posterior direction both in Task A and B but not in the mediolateral direction. Both in step errors and accuracy, no interaction effects of age and trial were shown. Our results suggest that old adults could not cope with rapid and direct task changes in our voluntary gait adaptability task as young adults. Since the significant main effect of trial for Task B, but not Task A appears to be due to different task complexity, further studies may determine the effect of task complexity or task switch timing.
Dapagliflozin reduces risk of heart failure rehospitalization in diabetic acute myocardial infarction patients: a propensity score-matched analysis
Authors: Mao Lipeng , Cai Dabei , Chi Boyu , Xiao Tingting , Zou Ailin , Wang Yu , Chen Qianwen , Gu Qingqing , Wang Qingjie , Ji Yuan , Sun Ling 
Published: April 2023

Abstract
Objective
The aim of this study was to investigate the effect of dapagliflozin (DAPA) on the rate of heart failure rehospitalization in patients with acute myocardial infarction (AMI) and type 2 diabetes mellitus (T2DM).

Methods
AMI patients with T2DM from CZ-AMI registry between January 2017 and January 2021 were enrolled in this study. Patients were stratified into DAPA users and non-DAPA users. The primary outcome was the incidence of heart failure rehospitalization. Kaplan–Meier analysis and Cox regressions were performed to evaluate the prognostic significance of DAPA. Propensity score matching (PSM) was performed to minimize the bias of confounding factors and facilitate the comparability between groups. The enrolled patients were matched with a propensity score of 1:1.

Results
A total of 961 patients were included, and 132 (13.74%) heart failure rehospitalizations occurred during a median follow-up of 540 days. In the Kaplan–Meier analysis, DAPA users had a statistically significantly lower rate of heart failure rehospitalization than non-DAPA users (p < 0.0001). Multivariate Cox analysis showed that DAPA was an independent protective factor for heart failure rehospitalization risk after discharge (HR = 0.498, 95% CI = 0.296 ~ 0.831, p = 0.001). After 1:1 propensity score matching, survival analysis showed a lower cumulative risk of heart failure rehospitalization in DAPA users than in non-DAPA users (p = 0.0007). In-hospital and continued use of DAPA remained significantly associated with a reduced risk of heart failure rehospitalization (HR = 0.417, 95% CI = 0.417 ~ 0.838, p = 0.001). Results were consistent across sensitivity and subgroup analyses.

Conclusion
In patients with diabetic AMI, in-hospital and continued use of DAPA after discharge were associated with a significant lower risk of heart failure rehospitalization.
A Paper‐Based Simulation Model for Teaching Inguinal Hernia Anatomy
Authors: Kong Chia Yew , Iddles Emma , Glen Paul 
Published: April 2023

AbstractBackgroundInguinal hernias remain a challenging area of learning for medical students due to its relatively complex anatomy. Modern curriculum delivery methods are conventionally limited to didactic lectures and demonstration of anatomy intraoperatively. These strategies have limitations; lectures are inherently descriptive and based on 2‐dimensional models, while intraoperative teaching is often unstructured and opportunistic.MethodsA paper‐based model was developed comprising three overlapping paper panels simulating the anatomical layers of the inguinal canal which can be modified readily to further simulate various hernia pathologies and their surgical repair. These models were incorporated into a timetabled structured learning session for 3rd‐ and 4th‐year medical students. Learners responded to fully anonymised surveys before and after the learning session.FindingsA total of 45 students participated in these sessions over a period of 6 months. Pre‐learning session mean ratings for the learners’ confidence in their understanding of the layers of the inguinal canal, identifying indirect and direct inguinal hernias and in naming the contents of the inguinal canal were 2.5, 3.3 and 2.9, while post‐learning session mean ratings were 8.0, 9.4 and 8.2, respectively. Paired samples Student's t‐tests for all three questions were statistically significant (p < 0.001). The mean rating for usefulness of the session was 9.6/10. Free comments from students emphasised the models’ usefulness as a visual learning aid.Discussion and ConclusionOur novel, low‐cost paper model was associated with an improvement in learners’ perceived knowledge and understanding of inguinal canal anatomy and pathology.
Surufatinib-induced renal thrombotic microangiopathy: first case report and review of literature
Authors: Zhu Wenjiao , Wang Wei , Shi Yuanping , Shen Bo , Li Yan 
Published: April 2023

AbstractAngiogenesis inhibitors such as tyrosine kinase inhibitors (TKIs) are common therapeutics currently used to treat oncologic disease. Surufatinib is a novel, small-molecule multiple receptor TKI approved by the National Medical Products Administration (NMPA) for the treatment of progressive, advanced, and well-differentiated pancreatic and extrapancreatic neuroendocrine tumours (NETs). Thrombotic microangiopathy (TMA) is a well-documented complication of TKIs targeting the VEGF-A/VEGFR2 signalling pathway. Here, we describe a 43-year-old female patient with biopsy-proven TMA and nephrotic syndrome due to surufatinib treatment for adenoid cystic carcinoma. Histological lesions included glomerular endothelial swelling, widening of subendothelial spaces, mesangiolysis, and double contour, which caused nephrotic proteinuria. Effective management was achieved by drug withdrawal and oral anti-hypertensive regents. The management of surufatinib-related nephrotoxicity without compromising its anticancer effects is challenging. Hypertension and proteinuria must be closely monitored during drug use to reduce or stop the dose in a timely manner before severe nephrotoxicity occurs.
Video-based tools for surgical quality assessment of technical skills in laparoscopic procedures: a systematic review
Authors: Grüter Alexander A. J. , Van Lieshout Annabel S. , van Oostendorp Stefan E. , Henckens Sofie P. G. , Ket Johannes C. F. , Gisbertz Suzanne S. , Toorenvliet Boudewijn R. , Tanis Pieter J. , Bonjer Hendrik J. , Tuynman Jurriaan B. 
Published: April 2023

AbstractBackgroundQuality of surgery has substantial impact on both short- and long-term clinical outcomes. This stresses the need for objective surgical quality assessment (SQA) for education, clinical practice and research purposes. The aim of this systematic review was to provide a comprehensive overview of all video-based objective SQA tools in laparoscopic procedures and their validity to objectively assess surgical performance.MethodsPubMed, Embase.com and Web of Science were systematically searched by two reviewers to identify all studies focusing on video-based SQA tools of technical skills in laparoscopic surgery performed in a clinical setting. Evidence on validity was evaluated using a modified validation scoring system.ResultsFifty-five studies with a total of 41 video-based SQA tools were identified. These tools were used in 9 different fields of laparoscopic surgery and were divided into 4 categories: the global assessment scale (GAS), the error-based assessment scale (EBAS), the procedure-specific assessment tool (PSAT) and artificial intelligence (AI). The number of studies focusing on these four categories were 21, 6, 31 and 3, respectively. Twelve studies validated the SQA tool with clinical outcomes. In 11 of those studies, a positive association between surgical quality and clinical outcomes was found.ConclusionThis systematic review included a total of 41 unique video-based SQA tools to assess surgical technical skills in various domains of laparoscopic surgery. This study suggests that validated SQA tools enable objective assessment of surgical performance with relevance for clinical outcomes, which can be used for training, research and quality improvement programs.