bluuebunny/crossref_metadata_2025_split huggingface dataset:
SYST-22 INTEGRATING GENE DEPENDENCY INTO A PEDIATRIC-FOCUSED CANCER DATA PORTAL FOR TARGETED THERAPY AND BIOMARKER DISCOVERY
Authors: Sun Claire , Ajith Vikesh , Panday Monty , Firestein Ron 
Published: August 2023

Abstract
Pediatric solid cancers, particularly those affecting the central nervous system (CNS), are the leading cause of disease-related deaths in children. Despite significant efforts to sequence pediatric solid tumors, they exhibit a "quiescent genome" with a considerably lower mutational burden than adult cancers. This leads to fewer actionable drug targets and poor response to cancer immunotherapy agents, including checkpoint inhibitors. As a result, it is imperative to move beyond genetic alterations and adopt a combination of functional and integrative approaches to develop novel, targeted treatments that are specifically designed for pediatric cancers. Over the past five years, the Next-Gen Precision Medicine Program team has devoted its efforts to establishing the Childhood Cancer Model Atlas (CCMA) (Sun, Daniel et al. Cancer Cell 2023). The CCMA is the largest collection of high-risk pediatric solid tumor cell lines globally, presenting a tremendous opportunity to integrate molecular features with functional dependencies using state-of-the-art computational approaches. However, the analysis of -omics level data is often limited to laboratories with specialized bioinformatics capabilities. Therefore, the establishment of the CCMA data portal with user-friendly analytical and visualization capabilities is essential to accelerate data-driven discovery and translational research in pediatric cancer on a global scale. The data portal is designed to simplify reporting, automate manual processes, and enhance the quality, usability, and longevity of the CCMA dataset. Its highlighted features concentrate on customized analysis, informative results, and user-friendly data visualization. Furthermore, by connecting the established models and their original tumor with clinical and molecular endpoints, the data portal enables clinical integration within the Australian molecular tumor board framework. This analytical data portal will enable the generation of new research hypotheses, prioritizes therapeutic opportunities, and supports international collaborative efforts in pediatric cancer.
SYST-25 MICROGLIA-SECRETED LIPID SPECIES DRIVE GLIOMA INVASION
Authors: Pallares-Moratalla Carla , Guyot Mélanie , Weng Linqian , Planque Melanie , Fendt Sarah-Maria , Swinnen Johan , Lambrechts Diether , Bergers Gabriele 
Published: August 2023

Abstract
The capacity of gliomas, including GBMs, to invade and infiltrate normal brain tissues makes their complete surgical removal impossible. The most crucial survival predictor is still the extent of surgical resection, urging the need to identify treatments that block the invasive growth of glioma to improve surgical resection and overall survival. Using a combination of single-cell transcriptomics, lipidomics, and high-resolution spatial metabolomics in genetically engineered GBM mouse models, reminiscent of human disease, and validation in human GBM samples, we found that 1) tumor cells infiltrating the normal brain parenchyma associate with and activate specific pathways in microglial cells (MGs), the residential brain macrophages. In turn, MGs undergo metabolic rewiring and secrete lipid species that promote glioma invasion of the different GBM subtypes by activating distinct signaling cues. Thus, blocking the MG-tumor cell axis or metabolic MG rewiring targets several GBM types and, in combination with standard therapy, results in small circumscribed tumors that should be easier excised and lead to a substantial increase in progression-free survival in glioma patients.
Impact of E-liquid Packaging on Vaping Product Perceptions Among Youth in England, Canada, and the United States: A Randomized Online Experiment
Authors: Simonavičius Erikas , East Katherine , Taylor Eve , Nottage Matilda , Reid Jessica L , Arnott Deborah , Bunce Laura , McNeill Ann , Hammond David 
Published: August 2023

Abstract

Introduction
Vaping is not risk-free but can help those who smoke to reduce harm to health and stop smoking. However, packaging of vaping products, including e-liquids, appeals to youth and might facilitate vaping among nicotine-naïve people. Standardized packaging of vaping products could moderate the appeal of vaping among youth. This study assessed how youth interest in trying and perceived health harms of using e-liquids are associated with branded or standardized (white or olive) e-liquid packaging with different nicotine levels displayed.

Aims and Methods
A between-subject experiment with three packaging and two nicotine level conditions included youth (n = 13801) aged 16 to 19 from England, Canada, and the United States as a part of a cross-sectional online survey in August–September 2021. Participants’ interest in trying and perceived harm of e-liquids were analyzed using logistic and multinomial regressions adjusted for age, sex, race or ethnicity, country, vaping, and smoking status.

Results
Compared with branded e-liquid packs, more youth reported no interest in trying e-liquids in white (aOR = 1.48, 95% CI = 1.34 to 1.64) or olive (aOR = 1.62, 95% CI: 1.47 to 1.80) standardized packs. Compared with branded e-liquid packs, more youth inaccurately perceived e-liquids in white (aOR = 1.22, 95% CI: 1.11 to 1.34) or olive (aOR = 1.29, 95% CI: 1.18 to 1.41) standardized packs as equally or more harmful than smoking. E-liquid nicotine levels displayed on packs were not associated with youth interest in trying or harm perceptions of using e-liquids.

Conclusions
Among 16- to 19-year-old youth from England, Canada, and the United States, standardized packaging of e-liquids was associated with lower interest in trying and higher health risk perceptions.

Implications
Branded packaging of vaping products appeal to youth and might prompt nicotine use among those who had never smoked. This study suggests that restricting branding elements on e-liquid packaging is associated with youth's lower interest in trying e-liquids and higher misperceptions that vaping is equally or more harmful than smoking. Standardized packaging might reduce appeal of vaping among youth, but its potential to discourage vaping for harm reduction should also be considered.
Charitable donations to natural disasters: evidence from an online platform
Authors: Jayaraman Rajshri , Kaiser Michael , Teirlinck Marrit 
Published: August 2023

Abstract
We investigate the demand and supply of charitable donations to natural disasters on a large online platform. We document that the bulk of charitable donations goes to a tiny fraction of natural disasters, which tend to be severe disasters that receive media coverage. Charities do not fundraise for the remaining 96% of disasters, which account for 80% of casualties. Using an event study-type design to explore temporal patterns in charitable donations, we find that fundraising and giving for disaster relief occur in a timely fashion, but that both are effectively absent for disasters that occur within a 2-month window of large disasters which have attracted massive funding. We also find no evidence that donations to disasters crowd out those to other charitable causes.
Plastid Nucleoids: Insights into Their Shape and Dynamics
Authors: Nishimura Yoshiki 
Published: August 2023

Abstract
Chloroplasts/plastids are unique organelles found in plant cells and some algae and are responsible for performing essential functions such as photosynthesis. The plastid genome, consisting of circular and linear DNA molecules, is packaged and organized into specialized structures called nucleoids. The composition and dynamics of these nucleoids have been the subject of intense research, as they are critical for proper plastid functions and development. In this mini-review, recent advances in understanding the organization and regulation of plastid nucleoids are overviewed, with a focus on the various proteins and factors that regulate the shape and dynamics of nucleoids, including DNA-binding proteins and membrane anchorage proteins. The dynamic nature of nucleoid organization, which is influenced by a variety of developmental cues and the cell cycle, is also examined.
A brief review of contrastive learning applied to astrophysics
Authors: Huertas-Company Marc , Sarmiento Regina , Knapen Johan H 
Published: August 2023

Abstract
Reliable tools to extract patterns from high-dimensionality spaces are becoming more necessary as astronomical data sets increase both in volume and complexity. Contrastive Learning is a self-supervised machine learning algorithm that extracts informative measurements from multidimensional data sets, which has become increasingly popular in the computer vision and Machine Learning communities in recent years. To do so, it maximizes the agreement between the information extracted from augmented versions of the same input data, making the final representation invariant to the applied transformations. Contrastive Learning is particularly useful in astronomy for removing known instrumental effects and for performing supervised classifications and regressions with a limited amount of available labels, showing a promising avenue towards Foundation Models. This short review paper briefly summarizes the main concepts behind contrastive learning and reviews the first promising applications to astronomy. We include some practical recommendations on which applications are particularly attractive for contrastive learning.
Targeting B cells for treatment of systemic sclerosis
Authors: Terui Hitoshi , Segawa Yuichiro , Asano Yoshihide 
Published: August 2023

Purpose of review
The pathogenesis of systemic sclerosis (SSc) has been linked to dysfunctional B cells as demonstrated in previous research. This review aims to show the evidence and ongoing clinical trials of B cell-targeted therapy and overview the various aspects of B cell involvement in SSc.

Recent findings
We provide an overview of the current understanding and therapeutic strategies targeting B cells in SSc patients. Several molecular targets of B cells have been identified for treating SSc, including CD20, CD19, B-cell activating factor (BAFF), and proteasome.

Summary
Many clinical trials have demonstrated that B cells play a critical role in the pathogenesis of SSc and may be a potential therapeutic target to improve disease symptoms. Although large-scale clinical studies are needed, various B cell-targeted therapies have the potential to address the unmet needs of SSc patients.
Comparison of clinical features and outcomes of proliferative, fibrotic, and mixed subtypes of IgG4-related disease: A retrospective cohort study
Authors: Peng Linyi , Zhang Xinlu , Zhou Jiaxin , Li Jieqiong , Liu Zheng , Lu Hui , Peng Yu , Fei Yunyun , Zhao Yan , Zeng Xiaofeng , Zhang Wen 
Published: August 2023

Abstract

Background:
Immunoglobulin G4-related disease (IgG4-RD) is a recently recognized immune-mediated disorder that can affect almost any organ in the human body. IgG4-RD can be categorized into proliferative and fibrotic subtypes based on patients' clinicopathological characteristics. This study aimed to compare the clinical manifestations, laboratory findings, and treatment outcomes of IgG4-RD among different subtypes.

Methods:
We prospectively enrolled 622 patients with newly diagnosed IgG4-RD at Peking Union Medical College Hospital from March 2011 to August 2021. The patients were divided into three groups according to their clinicopathological characteristics: proliferative, fibrotic, and mixed subtypes. We compared demographic features, clinical manifestations, organ involvement, laboratory tests, and treatment agents across three subtypes. We then assessed the differences in treatment outcomes among 448 patients receiving glucocorticoids alone or in combination with immunosuppressants. Moreover, risk factors of relapse were revealed by applying the univariate and multivariate Cox regression analysis.

Results:
We classified the 622 patients into three groups consisting of 470 proliferative patients, 55 fibrotic patients, and 97 mixed patients, respectively. We found that gender distribution, age, disease duration, and frequency of allergy history were significantly different among subgroups. In terms of organ involvement, submandibular and lacrimal glands were frequently involved in the proliferative subtype, while retroperitoneum was the most commonly involved site in both fibrotic subtype and mixed subtype. The comparison of laboratory tests revealed that eosinophils (P = 0.010), total IgE (P = 0.006), high-sensitivity C-reactive protein (P <0.001), erythrocyte sedimentation rate (P <0.001), complement C4 (P <0.001), IgG (P = 0.001), IgG1 (P <0.001), IgG4 (P <0.001), and IgA (P <0.001), at baseline were significantly different among three subtypes. Compared with proliferative and mixed subtypes, the fibrotic subtype showed the lowest rate of relapse (log-rank P = 0.014).

Conclusions:
Our study revealed the differences in demographic characteristics, clinical manifestations, organ involvement, laboratory tests, treatment agents, and outcomes across proliferative, fibrotic, and mixed subtypes in the retrospective cohort study. Given significant differences in relapse-free survival among the three subtypes, treatment regimens, and follow-up frequency should be considered separately according to different subtypes.
Free Flap Surgery Outcome Related to Antithrombotic Treatment Regime: An Analysis of 1000 Cases
Authors: Jakobsson Stina , Kamali Alexander , Edsander Nord Åsa , Sommar Pehr , Halle Martin 
Published: August 2023

Background:
Autologous free tissue transfer is today an integral part of reconstructive plastic surgery, but still lacks generally accepted guidelines regarding antithrombotic agents. We hypothesized that the overuse of antithrombotic agents could be a risk factor for free flap complications and therefore studied a treatment protocol adjustment.

Methods:
Consecutive free flaps between 2005 and 2020 at a single center were analyzed for complications in relation to the use of pre- and intraoperative treatment with three different antithrombotic agents. The use of preoperative low molecular weight heparin (LMWH), intraoperative heparin, and dextran were analyzed in relation to outcome variables, thromboembolic events, or reexploration for hematoma.

Results:
Nine hundred thirty-one patients underwent 1000 microvascular free flaps for breast (n = 487), head and neck (n = 365), and extremity (n = 148) reconstruction. Within the first postoperative week, 44 cases had a thromboembolic event and 58 cases underwent hematoma-related reexploration. In the multivariate analysis, thromboembolic events were associated with extremity reconstruction (P = 0.02) and smoking (P = 0.02). Hematoma-related reexploration was more common with triple antithrombotic therapy compared with all other treatment regimes (P < 0.05). The number of antithrombotic agents used perioperatively was linearly decreased, from three to none, over the elapsed time period (P < 0.001).

Conclusions:
Hematoma was the most common reason for reexploration and was further associated with the use of multiple antithrombotic agents. Cessation of triple treatment was associated with less hematomas and further reduction of antithrombotic agents did not result in any increase of thromboembolic events. Evidence-based guidelines are warranted for antithrombotic regimes in standard free flap surgery.
Does Initial Cleft Lip Width Predict Final Aesthetic Outcome?
Authors: Yang Jenny F. , Smetona John , Lopez Joseph , Peck Connor , Pourtaheri Navid , Steinbacher Derek M. 
Published: August 2023

Background:
A natural aesthetic appearance of the lip and a favorable scar are essential goals of cleft lip repair. Wider clefts intuitively pose a greater technical challenge; however, the relationship between initial width and aesthetic outcome remains controversial. The current study aimed to determine whether lip adhesion can help wider clefts achieve safe, consistent aesthetic outcomes.

Methods:
A retrospective cohort study was conducted on unilateral cleft lip patients who underwent lip repair within a 2-year period by the senior author. Subjects were divided into three groups based on cleft severity: (1) wide complete clefts that required lip adhesion before definitive repair, (2) narrower complete clefts that did not require lip adhesion, and (3) incomplete clefts. Aesthetic outcomes related to the vermillion and upper lip scar were rated by 48 blinded observers. Statistical analysis was performed using Kruskal-Wallis and Mann-Whitney tests. Nasal outcomes were not assessed.

Results:
Seventeen patients were included in the study: five in group 1, six in group 2, and six in group 3. Patients with the widest clefts did not have inferior results compared with the other groups. In fact, they had statistically significantly higher aesthetic scores in all scar-related outcomes compared with those in groups 2 and 3 (P < 0.0001).

Conclusions:
This study suggests that a wide cleft does not necessarily foreshadow a poor surgical outcome. In fact, wide clefts may have pleasing results, and the use of a staged lip adhesion approach can be useful for achieving the desired outcome in wider clefts.
Practical Review on Delayed Primary Closure: Basic Science and Clinical Applications
Authors: ElHawary Hassan , Covone Jason , Abdulkarim Shafic , Janis Jeffrey E. 
Published: August 2023

Summary:
Wound healing complications present a significant burden on both patients and health-care systems, and understanding wound healing principles is crucial across medical and surgical specialties to help mitigate such complications. One of these longstanding principles, specifically delayed primary closure (DPC), described as mechanically closing a wound after several days of secondary intention healing, lacks clear consensus on its definition, indications, and outcomes. This practical review examines wound healing fundamentals, focusing on DPC, its execution, indications, and comparative outcomes. A PubMed literature search was conducted to retrieve studies on DPC. Inclusion criteria included comparative studies assessing outcomes and complications between DPC and other closure techniques, as well as articles investigating DPC’s underlying physiology. Twenty-three comparative studies met inclusion criteria. DPC wounds have significantly higher partial pressure of oxygen, higher blood flow, and higher rates of collagen synthesis and remodeling activity, all of which help explain DPC wounds’ superior mechanical strength. DPC seems most beneficial in contaminated wounds, such as complicated appendectomies, postcardiac surgery wounds, and complicated abdominal wall reconstructions, where it has been associated with lower rates of surgical site infections. This practical review provides an evidence-based approach to DPC, its physiology, technique, and indications. Based on the existing literature, the authors recommend that DPC wounds should be dressed in saline/betadine soaks, changed and irrigated daily, with delayed closure lasting between 3 and 5 days or until the infection has resolved. The clearest indications for DPC are in the context of contaminated abdominal surgery and sternal wound dehiscence post cardiac surgery.
LANCL1, a cell surface protein, promotes liver tumor initiation through FAM49B-Rac1 axis to suppress oxidative stress
Authors: Huang Hongyang , Tsui Yu-Man , Ho Daniel Wai-Hung , Chung Clive Yik-Sham , Sze Karen Man-Fong , Lee Eva , Cheung Gary Cheuk-Hang , Zhang Vanilla Xin , Wang Xia , Lyu Xueying , Ng Irene Oi-Lin 
Published: August 2023

Background and Aims:
HCC is an aggressive cancer with a poor clinical outcome. Understanding the mechanisms that drive tumor initiation is important for improving treatment strategy. This study aimed to identify functional cell membrane proteins that promote HCC tumor initiation.

Approach and Results:
Tailor-made siRNA library screening was performed for all membrane protein-encoding genes that are upregulated in human HCC (n = 134), with sphere formation as a surrogate readout for tumor initiation. Upon confirmation of membranous localization by immunofluorescence and tumor initiation ability by limiting dilution assay in vivo, LanC-like protein-1 (LANCL1) was selected for further characterization. LANCL1 suppressed intracellular reactive oxygen species (ROS) and promoted tumorigenicity both in vitro and in vivo. Mechanistically, with mass spectrometry, FAM49B was identified as a downstream binding partner of LANCL1. LANCL1 stabilized FAM49B by blocking the interaction of FAM49B with the specific E3 ubiquitin ligase TRIM21, thus protecting FAM49B from ubiquitin-proteasome degradation. The LANCL1-FAM49B axis suppressed the Rac1-NADPH oxidase-driven ROS production, but this suppression of ROS was independent of the glutathione transferase function of LANCL1. Clinically, HCCs with high co-expression of LANCL1 and FAM49B were associated with more advanced tumor stage, poorer overall survival, and disease-free survival. In addition, anti-LANCL1 antibodies targeting the extracellular N-terminal domain were able to suppress the self-renewal ability, as demonstrated by the sphere formation ability of HCC cells.

Conclusions:
Our data showed that LANCL1 is a cell surface protein and a key contributor to HCC initiation. Targeting the LANCL1-FAM49B-Rac1-NADPH oxidase-ROS signaling axis may be a promising therapeutic strategy for HCC.
Multiomics identifies metabolic subtypes based on fatty acid degradation allocating personalized treatment in hepatocellular carcinoma
Authors: Li Binghua , Li Yunzheng , Zhou Huajun , Xu Yanchao , Cao Yajuan , Cheng Chunxiao , Peng Jin , Li Huan , Zhang Laizhu , Su Ke , Xu Zhu , Hu Yue , Lu Jiaming , Lu Yijun , Qian Liyuan , Wang Ye , Zhang Yuchen , Liu Qi , Xie Yuanyuan , Guo Sheng , Mehal Wajahat Z. , Yu Decai 
Published: August 2023

Background and Aims:
Molecular classification is a promising tool for prognosis prediction and optimizing precision therapy for HCC. Here, we aimed to develop a molecular classification of HCC based on the fatty acid degradation (FAD) pathway, fully characterize it, and evaluate its ability in guiding personalized therapy.

Approach and Results:
We performed RNA sequencing (RNA-seq), PCR-array, lipidomics, metabolomics, and proteomics analysis of 41 patients with HCC, in which 17 patients received anti-programmed cell death-1 (PD-1) therapy. Single-cell RNA sequencing (scRNA-seq) was performed to explore the tumor microenvironment. Nearly, 60 publicly available multiomics data sets were analyzed. The associations between FAD subtypes and response to sorafenib, transarterial chemoembolization (TACE), immune checkpoint inhibitor (ICI) were assessed in patient cohorts, patient-derived xenograft (PDX), and spontaneous mouse model ls. A novel molecular classification named F subtype (F1, F2, and F3) was identified based on the FAD pathway, distinguished by clinical, mutational, epigenetic, metabolic, and immunological characteristics. F1 subtypes exhibited high infiltration with immunosuppressive microenvironment. Subtype-specific therapeutic strategies were identified, in which F1 subtypes with the lowest FAD activities represent responders to compounds YM-155 and Alisertib, sorafenib, anti-PD1, anti-PD-L1, and atezolizumab plus bevacizumab (T + A) treatment, while F3 subtypes with the highest FAD activities are responders to TACE. F2 subtypes, the intermediate status between F1 and F3, are potential responders to T + A combinations. We provide preliminary evidence that the FAD subtypes can be diagnosed based on liquid biopsies.

Conclusions:
We identified 3 FAD subtypes with unique clinical and biological characteristics, which could optimize individual cancer patient therapy and help clinical decision-making.