bluuebunny/crossref_metadata_2025 huggingface dataset:
Advancement in predictive biomarkers for gestational diabetes mellitus diagnosis and related outcomes: a scoping review
Authors: Rathnayake Hasini , Han Luhao , da Silva Costa Fabrício , Paganoti Cristiane , Dyer Brett , Kundur Avinash , Singh Indu , Holland Olivia J
Published: December 2024

Objective

Gestational diabetes mellitus (GDM) is a metabolic disorder associated with adverse maternal and neonatal outcomes. While GDM is diagnosed by oral glucose tolerance testing between 24–28 weeks, earlier prediction of risk of developing GDM via circulating biomarkers has the potential to risk-stratify women and implement targeted risk reduction before adverse obstetric outcomes. This scoping review aims to collate biomarkers associated with GDM development, associated perinatal outcome and medication requirement in GDM.

Design

The Preferred Reporting Items for Systematic Reviews and Meta-Analysis extension for scoping reviews was used to guide the study.

Data sources

This review searched for articles on PubMed, Embase, Scopus, Cochrane Central Register of Controlled Trials, the Cumulative Index to Nursing and Allied Health Literature and the Web of Science from January 2013 to February 2023.

Eligibility criteria

The eligibility criteria included analytical observational studies published in English, focusing on pregnant women with maternal plasma or serum biomarkers collected between 6 and 24 weeks of gestation. Studies were excluded if they evaluated drug effects, non-GDM diabetes types or involved twin pregnancies, microbiota, genetic analyses or non-English publications.

Data extraction and synthesis

Two independent reviewers extracted data. One reviewer extracted data from papers included in the scoping review using Covidence. From the 8837 retrieved records, 137 studies were included.

Results

A total of 278 biomarkers with significant changes in individuals with GDM compared with controls were identified. The univariate predictive biomarkers exhibited insufficient clinical sensitivity and specificity for predicting GDM, perinatal outcomes, and the necessity of medication. Multivariable models combining maternal risk factors with biomarkers provided more accurate detection but required validation for use in clinical settings.

Conclusion

This review recommends further research integrating novel omics technology for building accurate models for predicting GDM, perinatal outcome, and the necessity of medication while considering the optimal testing time.
Processes of obstetrical care and outcomes among Ontario physicians versus non-physicians: a population-based study
Authors: Simpson Andrea N , Sutradhar Rinku , McArthur Eric , Cusimano Maria C , Baxter Nancy N
Published: December 2024

Objective

We compared processes of antepartum, intrapartum and postpartum care and obstetrical outcomes between physicians and non-physicians.

Design

This is a population-based retrospective matched cohort study.

Setting

The study was conducted in Ontario, Canada.

Participants

Physicians and non-physicians residing in high-income urban areas from 1 April 2009 to 26 November 2018 were included. Physicians were matched to non-physicians on maternal age, calendar year, parity, conception by assisted reproductive technology and singleton versus multifetal gestation. We compared processes of antepartum, intrapartum and postpartum care between physicians and non-physicians.

Outcome measures

The primary outcome was mode of delivery (caesarean section, C-section vs vaginal delivery). Secondary outcomes included obstetrical anal sphincter injury among those experiencing vaginal birth and differences in urgent healthcare contacts (maternal and neonatal) during the postpartum period.

Results

7327 physicians were matched 1:5 to 36 185 non-physicians and were well balanced except for comorbidities (physicians had fewer comorbidities). Physicians had more antenatal ultrasounds and invasive prenatal testing, received labour anaesthesia more often and were more often delivered by their own care provider. In adjusted analyses, physicians and non-physicians had a similar risk of C-section (aRR 0.97, 95% CI 0.93 to 1.00, p=0.07). There was no difference in neonatal urgent care contacts; non-physicians had a higher risk of maternal urgent postpartum care (adjusted relative risk [aRR] 1.22, 95% CI 1.08 to 1.37, p<0.0001).

Conclusions

Physicians and non-physicians of similar age and with similar pregnancy characteristics had a comparable rate of C-section, which may be related to a lack of cost drivers for C-section in Ontario.
Polysaccharide from Scutellaria baicalensis Georgi alleviates ulcerative colitis in mice by maintaining the intestinal barrier integrity via MLC/Notch signaling
Authors: Xiao Liang , Chen Yongpo , Li Xiaoqing , Li Shuwei , Tang Wenjie , Yan Jiayou , Wei Xiaolan , Zhou Mengjia , Huang Chongbo , Diao Hui
Published: December 2024

Ulcerative colitis is a chronic idiopathic inflammatory bowel disease (IBD) that seriously impacts human health. So far, little information has been reported on the possible benefits of polysaccharides from Scutellaria baicalensis Georgi (SBGP) in alleviating colitis. Therefore, our study investigated the potential therapeutic effects of SBGP on mice with DSS-induced colitis. Results showed that SBGP administration ameliorated the severity of clinical symptoms and enhanced immunomodulatory effects in dextran sulfate sodium (DSS)-treated mice. Additionally, SBGP was found to regulate the inflammatory response, improve mucosal barrier integrity, and maintain tight junctions in the colonic epithelium. Furthermore, SBGP was found to restrain the activation of Notch and MLCK/MLC signaling pathways, which play important roles in inflammation and epithelial barrier homeostasis. These findings suggest that SBGP may have therapeutic potential for the treatment of colitis and other IBD.
Unveiling Poncet Disease: A Rare Presentation with Multiple Tubercular Foci in the Hand and Spine of an Older Patient: A Case Report
Authors: HASHIMOTO Kazuhiko , MORI Shigeshi , IKEDA Terumasa , GOTO Koji
Published: December 2024

Poncet disease (PD) is a rare form of reactive polyarthritis associated with acute tuberculosis (TB). Multiple TB foci are rare in PD, particularly on the hands. Herein, we describe a case of PD with foci in the trapezium and spine of a 76-year-old man. His medical history included knee arthritis as well as hand and lumbar pain. Radiography and magnetic resonance imaging revealed lytic lesions in the trapezium and spine, which were suspected to be caused by TB infection. An open biopsy of the trapezium and spine was performed. The biopsy results revealed dry necrosis and epithelioid granulation. The diagnosis of PD was made, and the patient was referred to a TB specialty hospital. Our results highlight the importance of considering PD in older patients with multiple TB foci, especially on the hands.

Level of Evidence: Level V (Therapeutic)
TorchGeo: Deep Learning With Geospatial Data
Authors: Stewart Adam J. , Robinson Caleb , Corley Isaac A. , Ortiz Anthony , Lavista Ferres Juan M. , Banerjee Arindam
Published: December 2024

Remotely sensed geospatial data are critical for applications including precision agriculture, urban planning, disaster monitoring and response, and climate change research, among others. Deep learning methods are particularly promising for modeling many remote sensing tasks given the success of deep neural networks in similar computer vision tasks and the sheer volume of remotely sensed imagery available. However, the variance in data collection methods and handling of geospatial metadata make the application of deep learning methodology to remotely sensed data nontrivial. For example, satellite imagery often includes additional spectral bands beyond red, green, and blue and must be joined to other geospatial data sources that may have differing coordinate systems, bounds, and resolutions. To help realize the potential of deep learning for remote sensing applications, we introduce TorchGeo, a Python library for integrating geospatial data into the PyTorch deep learning ecosystem. TorchGeo provides data loaders for a variety of benchmark datasets, composable datasets for uncurated geospatial data sources, samplers for geospatial data, and transforms that work with multispectral imagery. TorchGeo is also the first library to provide pre-trained models for multispectral satellite imagery (e.g., models that use all bands from the Sentinel-2 satellites), allowing for advances in transfer learning on downstream remote sensing tasks with limited labeled data. We use TorchGeo to create reproducible benchmark results on existing datasets and benchmark our proposed method for preprocessing geospatial imagery on the fly. TorchGeo is open source and available on GitHub: https://github.com/microsoft/torchgeo.
The Chromatic Number of Kneser Hypergraphs via Consensus Division
Authors: Haviv Ishay
Published: December 2024

We show that the Consensus Division theorem implies lower bounds on the chromatic number of Kneser hypergraphs, offering a novel proof for a result of Alon, Frankl, and Lovász and for its generalization by Kříž. Our approach is applied to study the computational complexity of the total search problem
Kneser

p

, which given a succinct representation of a coloring of a
p
-uniform Kneser hypergraph with fewer colors than its chromatic number asks to find a monochromatic hyperedge. We prove that for every prime
p
, the
Kneser

p

problem with an extended access to the input coloring is efficiently reducible to a quite weak approximation of the Consensus Division problem with
p
shares. In particular, for
p
=2, the problem is efficiently reducible to
any non-trivial
approximation of the Consensus Halving problem on normalized monotone functions. We further show that for every prime
p
, the
Kneser

p

problem lies in the complexity class
PPA
-p
. As an application, we establish limitations on the complexity of the
Kneser

p

problem, restricted to colorings with a bounded number of colors.
Extracellular matrix instability and chronic inflammation underlie maladaptive right ventricular pressure overload remodeling and failure in male mice
Authors: Russo Ilaria , Dun Wen , Mehta Swasti , Ahmed Sowda , Tzimas Christos , Fukuma Nobuaki , Tsai Emily J.
Published: December 2024

We compared pressure overload-induced RV remodeling in adult male versus female mice subjected to PAB. This study discovered an association between severe RVD, RVF, ECM instability, and chronic inflammation in pressure-overloaded RV of male PAB mice. These features distinguished maladaptive RV remodeling in male from adaptive RV remodeling in female PAB mice. In male patients with RV pressure overload due to HF or PAH, enhancing ECM stability and countering the recruitment of macrophages may help preserve RV function such that RVF could be prevented or delayed.
Trans-retinal predictive signals of visual features are precise, saccade-specific and operate over a wide range of spatial frequencies
Authors: Grzeczkowski Lukasz , Stein Arne , Rolfs Martin
Published: December 2024

Across a saccadic eye movement, the visual system is able to keep track of the signals carrying the visual features of a saccade target. We provide evidence that these signals are sensitive to a wide range of stimulus sizes, can use a wide range spatial frequencies channels and, operate at various saccade amplitudes. Our results suggest an underlying mechanism operating beyond the magnocellular pathway that is contingent to saccade execution.
Revealing the Therapeutic Potential of Stem Cells in Burn Healing: A Deeper Understanding of the Therapeutic Mechanisms of Epidermal Stem Cells and Mesenchymal Stem Cells
Authors: Lu Jianyu , Zhang Wei , Zhu Yushu , Luo Pengfei , Tong Xirui , Xie Sujie , Jiang Luofeng , Guo Xinya , Huang Jie , Gu Minyi , Ding Xinran , Xian Shuyuan , Huang Runzhi , Ji Shizhao , Xia Zhaofan
Published: December 2024

Background: Burns are a global public health issue and a major cause of disability and death around the world. Stem cells, which are the undifferentiated cells with the potential for indefinite proliferation and multilineage differentiation, have the ability to replace injured skin and facilitate the wound repair process through paracrine mechanisms. In light of this, the present study aims to conduct a bibliometric analysis in order to identify research hotspots of stem cell–related burns and assess global research tendencies.

Methods: To achieve this objective, we retrieved scientific publications on burns associated with stem cells covering the period from January 1, 1978, to October 13, 2022, from the Web of Science Core Collection (WoSCC). Bibliometric analyses, including production and collaboration analyses between countries, institutions, authors, and journals, as well as keyword and topic analyses, were conducted using the bibliometrix R package, CiteSpace, and VOSviewer.

Results: A total of 1648 burns associated with stem cell documents were published and listed on WOSCC. The most contributive country, institution, journal, and author were the United States, LV Prasad Eye Institute, Burns, and Scheffer C.G. Tseng, respectively. More importantly, combined with historical direct citation network, trend topic analysis, keyword co‐occurrence network, and substantial literature analysis, we eventually summarized the research hotspots and frontiers on burns associated stem cell reasearch.

Conclusion: The present study obtained deep insight into the developing trends and research hotspots on burns associated with stem cells, which arouses growing concerns and implies increasing clinical implications. The mechanism and therapeutics of epidermal stem cells (ESCs) for burn wounds and the mechanism of mesenchymal stem cells (MSCs) and MSC‐derived exosomes for burns wounds are two research hotspots in this field.
Bioinformatics Analysis of Biomarkers and Therapeutic Targets Related to Necroptosis in Intervertebral Disc Degeneration
Authors: Zhang Fan , Yuan Lei , Ding Heng , Lou Zhenkai , Li Xingguo
Published: December 2024

Necroptosis is a critical process in intervertebral disc degeneration (IDD). This research is aimed at identifying key genes regulating necroptosis in IDD to provide a theoretical basis for early diagnosis and treatment. Transcriptome data from patients with IDD and normal samples were obtained from the GSE34095 and GSE124272 datasets of the Gene Expression Omnibus (GEO) public database. Necroptosis‐related genes (NRGs) were sourced from the GeneCards database and literature. Differentially expressed necroptosis‐related genes (DE‐NRGs) in IDD were identified by intersecting these sources. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) were used for gene annotation analysis. The receiver operating characteristic (ROC) curve and nomogram analyses assessed the diagnostic efficiency of DE‐NRGs. The miRWalk and starBase databases helped construct the competing endogenous RNA (ceRNA) regulatory network of DE‐NRGs. We identified 517 differential genes in tissue and 2974 in blood, with 62 genes in common. DE‐NRGs (AIFM1, CCT8, HNRNPA1, KHDRBS1, SERBP1) were identified by intersecting NRGs with these 62 common genes. The ROC curve showed an area under the curve (AUC) > 0.70 for DE‐NRGs, and the nomogram indicated that a higher DE‐NRG score correlates with a higher risk of IDD. CCT8, KHDRBS1, and AIFM1 emerged as potential therapeutic targets for IDD through target drug prediction. qRT‐PCR (quantitative reverse transcription polymerase chain reaction), Western blot, and immunohistochemistry confirmed the expression of AIFM1, CCT8, HNRNPA1, KHDRBS1, and SERBP1 in patients’ nucleus pulposus tissue, suggesting these genes as key targets for IDD risk assessment and drug therapy.
Mineral Composition, Phenolic Content and Antibacterial Activity of Aqueous and Organic Extracts of Wild Morchella esculenta (L.) Pers. From the Province of Taza, Morocco
Authors: Mahtal Asmae , Lamchouri Fatima , Toufik Hamid
Published: December 2024

In the context of the valorisation of edible mushrooms from the province of Taza, Morocco, the present study, carried out for the first time, aims to evaluate the mineral composition, phenolic content, antibacterial activity and self‐preservation potential of wild Morchella esculenta (L.) Pers. from Taza. Inductively coupled plasma atomic emission spectrometry (ICP‐AES) determined the mineral salt content. We performed aqueous extractions using decoction, infusion and maceration, as well as hot and cold organic extractions with ethanol, acetone and diethyl ether. We then carried out a qualitative and quantitative analyses of the chemical composition. The antibacterial activity of the aqueous and organic extracts was studied using the disc diffusion method and by determining minimum inhibitory concentrations (MICs) and bactericidal concentrations (MBCs). Principal component analysis (PCA) was used to analyse the correlation between the chemical composition and antibacterial activity. Mineral analysis showed that the mushroom is rich in minerals, especially K (3578.4), Fe (2969.16), P (1818.66) and Mg (183.657) mg/kg dry matter. Quantitative analysis showed that the diethyl ether extract had the highest flavonoid content (846.07 ± 1.87 mgEQ/gE), the aqueous macerated extract was the richest in polyphenols (20.51 ± 0.45 mg EAG/gE) and the acetone extract had the highest catechic tannin content (17.13 ± 1.10 mgEC/gE). A study on antibacterial activity demonstrated that the decocted was bactericidal against Proteus mirabilis, while the aqueous macerated extract was bactericidal against Bacillus subtilis. The macerated diethyl ether extract was bacteriostatic against Proteus mirabilis, whereas the ethanolic extract was bactericidal against Staphylococcus aureus. This study showed that this mushroom is abundant in minerals and phenolic compounds, demonstrating its nutritional and therapeutic interest. In addition, this mushroom has antibacterial potential, which provides it the ability to protect itself against infection by pathogenic bacteria during storage and commercialization. PCA correlated the richest extracts in phenolic compounds and antibacterial activity.
Sarcoidosis‐Like Reaction in Melanoma Patients Receiving Immunotherapy or Targeted Therapy
Authors: Murgia Giulia , Valtellini Luca , Nazzaro Gianluca , Passoni Emanuela , Scarfì Federica , Boggio Francesca , Marzano Angelo V. , Garrone Ornella , Denaro Nerina
Published: December 2024

This case series highlights the complexity of sarcoidosis‐like reactions (SLRs) during cancer treatment, specifically in patients receiving immunotherapy or targeted therapies for melanoma. SLRs can either mimic disease progression or present as part of the clinical manifestation, making diagnosis and treatment challenging. Our study reviewed the medical records of 31 patients who were candidates for postoperative treatment between June 2022 and June 2024. Out of these, three patients developed SLRs during their treatment. A 55‐year‐old woman with Stage IIIb cutaneous melanoma, receiving adjuvant therapy with anti‐PD‐1, after seven cycles of pembrolizumab, developed mediastinal node enlargement and skin hypodermic nodes. A biopsy of the hypodermic node revealed granulomatous infiltrates with sparse lymphocytes, consistent with sarcoidosis. A low dose of steroids was administered, resulting in a dramatic improvement. A 48‐year‐old woman with Stage IIIb BRAF wild‐type melanoma, receiving nivolumab every 4 weeks, developed systemic sarcoidosis after seven cycles, primarily affecting extrapulmonary sites. Despite the immune‐induced sarcoidosis, her treatment was not stopped, as decided by the multidisciplinary team (MDT). A 65‐year‐old man with Stage IIIb BRAF‐mutant melanoma, receiving dabrafenib and trametinib, developed lung and cutaneous sarcoidosis, presenting with symptoms that led to emergency department admission. In all cases, the MDT played a crucial role in determining the course of treatment and balancing the risks of continuing or suspending cancer therapies while managing SLRs. National and international guidelines were consulted, but tailored decisions by the MDT were essential for optimizing patient care.
Figures S1–4 and Tables S1–2 from Selective Enhancer Gain-of-Function Deregulates MYC Expression in Multiple Myeloma
Authors: Rahmat Mahshid , Clement Kendell , Alberge Jean-Baptiste , Sklavenitis-Pistofidis Romanos , Kodgule Rohan , Fulco Charles P. , Heilpern-Mallory Daniel , Nilsson Katarina , Dorfman David , Engreitz Jesse M. , Getz Gad , Pinello Luca , Ryan Russell J.H. , Ghobrial Irene M.
Published: December 2024

Supplementary Figures and Tables
Table S8 from Combined Autophagy Inhibition and Dendritic Cell Recruitment Induces Antitumor Immunity and Enhances Immune Checkpoint Blockade Sensitivity in Pancreatic Cancer
Authors: Oyama Koki , Nakata Kohei , Tsutsumi Chikanori , Hayashi Masataka , Zhang Bo , Mochida Yuki , Shinkawa Tomohiko , Hirotaka Kento , Zhong Pingshan , Date Satomi , Luo Haizhen , Kubo Akihiro , Higashijima Nobuhiro , Yamada Yutaka , Abe Toshiya , Ideno Noboru , Koikawa Kazuhiro , Iwamoto Chika , Ikenaga Naoki , Ohuchida Kenoki , Onishi Hideya , Morisaki Takashi , Kuba Keiji , Oda Yoshinao , Nakamura Masafumi
Published: December 2024

Top 30 DEGs for three CD8+ T cell clusters identified from scRNA-seq of CD45+ immune cells in KPC1 shNC / shATG7 transplanted syngeneic PDAC tumors
Table S3 from Combined Autophagy Inhibition and Dendritic Cell Recruitment Induces Antitumor Immunity and Enhances Immune Checkpoint Blockade Sensitivity in Pancreatic Cancer
Authors: Oyama Koki , Nakata Kohei , Tsutsumi Chikanori , Hayashi Masataka , Zhang Bo , Mochida Yuki , Shinkawa Tomohiko , Hirotaka Kento , Zhong Pingshan , Date Satomi , Luo Haizhen , Kubo Akihiro , Higashijima Nobuhiro , Yamada Yutaka , Abe Toshiya , Ideno Noboru , Koikawa Kazuhiro , Iwamoto Chika , Ikenaga Naoki , Ohuchida Kenoki , Onishi Hideya , Morisaki Takashi , Kuba Keiji , Oda Yoshinao , Nakamura Masafumi
Published: December 2024

Autophagy signature scores for each sample from the public PDAC patient scRNA-seq dataset
Figure S2 from Combined Autophagy Inhibition and Dendritic Cell Recruitment Induces Antitumor Immunity and Enhances Immune Checkpoint Blockade Sensitivity in Pancreatic Cancer
Authors: Oyama Koki , Nakata Kohei , Tsutsumi Chikanori , Hayashi Masataka , Zhang Bo , Mochida Yuki , Shinkawa Tomohiko , Hirotaka Kento , Zhong Pingshan , Date Satomi , Luo Haizhen , Kubo Akihiro , Higashijima Nobuhiro , Yamada Yutaka , Abe Toshiya , Ideno Noboru , Koikawa Kazuhiro , Iwamoto Chika , Ikenaga Naoki , Ohuchida Kenoki , Onishi Hideya , Morisaki Takashi , Kuba Keiji , Oda Yoshinao , Nakamura Masafumi
Published: December 2024

Autophagy inhibition in cancer cells triggers T-cell-mediated immune response
Table S3 from The Innate Immune System and the TRAIL–Bcl-XL Axis Mediate a Sex Bias in Lung Cancer and Confer a Therapeutic Vulnerability in Females
Authors: May Lauren , Hu Bin , Jerajani Preksha , Jagdeesh Akash , Alhawiti Ohud , Cai Lillian , Semenova Nina , Guo Chunqing , Isbell Madison , Deng Xiaoyan , Faber Anthony C. , Pillappa Raghavendra , Bandyopadhyay Dipankar , Wang Xiang-Yang , Neuwelt Alexander , Koblinski Jennifer , Bos Paula D. , Li Howard , Martin Rebecca , Landry Joseph W.
Published: December 2024

Supplementary Table 3: Statistical Analysis of Multicolor Flow Cytometry Characterization of Tumors.
Supplementary Table 6 from Induction of the TEAD Coactivator VGLL1 by Estrogen Receptor–Targeted Therapy Drives Resistance in Breast Cancer
Authors: Gemma Carolina , Lai Chun-Fui , Singh Anup K. , Belfiore Antonino , Portman Neil , Milioli Heloisa Z. , Periyasamy Manikandan , Raafat Sara , Nicholls Alyssa J. , Davies Claire M. , Patel Naina R. , Simmons Georgia M. , Fan Hailing , Nguyen Van T.M. , Magnani Luca , Rakha Emad , Martin Lesley-Ann , Lim Elgene , Coombes R. Charles , Pruneri Giancarlo , Buluwela Laki , Ali Simak
Published: December 2024

Supplementary Table 6
Supplementary Data from The Innate Immune System and the TRAIL–Bcl-XL Axis Mediate a Sex Bias in Lung Cancer and Confer a Therapeutic Vulnerability in Females
Authors: May Lauren , Hu Bin , Jerajani Preksha , Jagdeesh Akash , Alhawiti Ohud , Cai Lillian , Semenova Nina , Guo Chunqing , Isbell Madison , Deng Xiaoyan , Faber Anthony C. , Pillappa Raghavendra , Bandyopadhyay Dipankar , Wang Xiang-Yang , Neuwelt Alexander , Koblinski Jennifer , Bos Paula D. , Li Howard , Martin Rebecca , Landry Joseph W.
Published: December 2024

Supplemental Figures 1-10
Supplementary Data from C-Reactive Protein Induces Immunosuppression by Activating FcγR2B in Pulmonary Macrophages to Promote Lung Metastasis
Authors: Feng Jun-Rui , Li Xue , Han Cong , Chang Yue , Fu Yu , Feng Gong-Chang , Lei Yutiantian , Li Hai-Yun , Tang Patrick Ming-Kuen , Ji Shang-Rong , Hou Yuzhu , Wu Yi
Published: December 2024

Supplementary Data
Data from Targeting Fatty Acid Metabolism Abrogates the Differentiation Blockade in Preleukemic Cells
Authors: Liu Xiaoyu , Liu Yu , Rao Qing , Mei Yihan , Xing Haiyan , Gu Runxia , Mou Junli , Chen Manling , Ding Fan , Xie Wanqing , Tang Kejing , Tian Zheng , Wang Min , Qiu Shaowei , Wang Jianxiang
Published: December 2024

Abstract
Metabolism plays a key role in the maintenance of normal hematopoietic stem cells (HSC) and in the development of leukemia. A better understanding of the metabolic characteristics and dependencies of preleukemic cells could help identify potential therapeutic targets to prevent leukemic transformation. As AML1–ETO, one of the most frequent fusion proteins in acute myeloid leukemia that is encoded by a RUNX1::RUNX1T1 fusion gene, is capable of generating preleukemic clones, in this study, we used a conditional Runx1::Runx1t1 knockin mouse model to evaluate preleukemic cell metabolism. AML1–ETO expression resulted in impaired hematopoietic reconstitution and increased self-renewal ability. Oxidative phosphorylation and glycolysis decreased significantly in these preleukemic cells accompanied by increased HSC quiescence and reduced cell cycling. Furthermore, HSCs expressing AML1–ETO exhibited an increased requirement for fatty acids through metabolic flux. Dietary lipid deprivation or loss of the fatty acid transporter FATP3 by targeted deletion using CRISPR/Cas9 partially restored differentiation. These findings reveal the unique metabolic profile of preleukemic cells and propose FATP3 as a potential target for disrupting leukemogenesis.

Significance: Fatty acid metabolism is required for maintenance of preleukemic cells but dispensable for normal hematopoiesis, indicating that dietary lipid deprivation or inhibiting fatty acid uptake may serve as potential strategies to prevent leukemogenesis.
Data from Targeting SHCBP1 Inhibits Tumor Progression by Restoring Ciliogenesis in Ductal Carcinoma
Authors: Shi Wengui , Li Lianshun , Zhao Huiming , Li Zhengyang , Ma Zhijian , Gu Qianlin , Ye Huili , Jiang Xiangyan , Dong Yuman , Qin Long , Zhou Huinian , Yu Zeyuan , Jiao Zuoyi
Published: December 2024

Abstract
Primary cilia detect and transmit environmental signals into cells. Primary cilia are absent in a subset of ductal carcinomas characterized by distinctive biological activities, and recovery of cilia with normal functionality has been shown to have therapeutic potential in some cancer types. Therefore, elucidation of the underlying mechanism and clinical significance of ciliary loss in ductal carcinomas could help develop effective treatment strategies. Here, we identified a link between Shc1-binding protein (SHCBP1) and cilia in ductal carcinomas. Shcbp1 knockout in transgenic mice profoundly impeded tumor progression and metastasis, prolonging survival. Single-cell transcriptome analysis revealed a functional connection between SHCBP1 deficiency and increased tumor ciliogenesis. SHCBP1 ablation restored ciliogenesis in unciliated ductal carcinoma by promoting the proximity between the midbody remnant (MBR) and centrosome through enhanced Rab8 GTPase activity and Rab8GTP positioning within the MBR. Inhibition of tumor progression by SHCBP1 loss relied on the recovery of ciliogenesis. Analysis of a large cohort of patients with ductal carcinoma revealed a negative correlation between SHCBP1-induced ciliary loss and patient prognosis. Restoring ciliogenesis via SHCBP1 ablation elicited therapeutic effects in patient-derived xenograft models. Together, this study delineates that induction of MBR-centrosome proximity through SHCBP1-deficiency reactivates ciliogenesis, offering unique opportunities for the treatment of unciliated ductal carcinomas.

Significance: SHCBP1 depletion rescues tumor ciliogenesis by enhancing Rab8 GTPase activity to restore the proximity of the  midbody remnant to the centrosome, which impedes progression of ductal carcinomas and suggests potential therapeutic strategies.
Supplementary Table S9 from Spatial Dynamics of T- and B-Cell Responses Predicts Clinical Outcome of Resectable and Unresectable Hepatocellular Carcinoma
Authors: Kurebayashi Yutaka , Sugimoto Katsutoshi , Tsujikawa Hanako , Matsuda Kosuke , Nomura Rui , Ueno Akihisa , Masugi Yohei , Yamazaki Ken , Effendi Kathryn , Takeuchi Hirohito , Itoi Takao , Hasegawa Yasushi , Abe Yuta , Kitago Minoru , Ojima Hidenori , Sakamoto Michiie
Published: December 2024

Table S9. Primers used in this study
Supplementary Table S8 from Spatial Dynamics of T- and B-Cell Responses Predicts Clinical Outcome of Resectable and Unresectable Hepatocellular Carcinoma
Authors: Kurebayashi Yutaka , Sugimoto Katsutoshi , Tsujikawa Hanako , Matsuda Kosuke , Nomura Rui , Ueno Akihisa , Masugi Yohei , Yamazaki Ken , Effendi Kathryn , Takeuchi Hirohito , Itoi Takao , Hasegawa Yasushi , Abe Yuta , Kitago Minoru , Ojima Hidenori , Sakamoto Michiie
Published: December 2024

Table S8. Details of multiplex immunohistochemistry panels and definition of each CD8 and CD4 T cell population
Supplementary Table S5 from Spatial Dynamics of T- and B-Cell Responses Predicts Clinical Outcome of Resectable and Unresectable Hepatocellular Carcinoma
Authors: Kurebayashi Yutaka , Sugimoto Katsutoshi , Tsujikawa Hanako , Matsuda Kosuke , Nomura Rui , Ueno Akihisa , Masugi Yohei , Yamazaki Ken , Effendi Kathryn , Takeuchi Hirohito , Itoi Takao , Hasegawa Yasushi , Abe Yuta , Kitago Minoru , Ojima Hidenori , Sakamoto Michiie
Published: December 2024

Table S5. Univariate analysis for PFS and OS in cases treated with Atezo+Bev therapy (n = 58)
Supplementary Document 1 from Large-Scale Comparative Analysis of Canine and Human Osteosarcomas Uncovers Conserved Clinically Relevant Tumor Microenvironment Subtypes
Authors: Patkar Sushant , Mannheimer Joshua , Harmon Stephanie A. , Ramirez Christina J. , Mazcko Christina N. , Choyke Peter L. , Brown Gregory Thomas , Turkbey Baris , LeBlanc Amy K. , Beck Jessica A.
Published: December 2024

Document containing Supplementary Table legends and supplementary Figures S1-S11
Supplementary Table S1 from Spatial Dynamics of T- and B-Cell Responses Predicts Clinical Outcome of Resectable and Unresectable Hepatocellular Carcinoma
Authors: Kurebayashi Yutaka , Sugimoto Katsutoshi , Tsujikawa Hanako , Matsuda Kosuke , Nomura Rui , Ueno Akihisa , Masugi Yohei , Yamazaki Ken , Effendi Kathryn , Takeuchi Hirohito , Itoi Takao , Hasegawa Yasushi , Abe Yuta , Kitago Minoru , Ojima Hidenori , Sakamoto Michiie
Published: December 2024

Table S1. Clinicopathological findings in Cohort 1 and 2
Supplementary Figure S9 from Spatial Dynamics of T- and B-Cell Responses Predicts Clinical Outcome of Resectable and Unresectable Hepatocellular Carcinoma
Authors: Kurebayashi Yutaka , Sugimoto Katsutoshi , Tsujikawa Hanako , Matsuda Kosuke , Nomura Rui , Ueno Akihisa , Masugi Yohei , Yamazaki Ken , Effendi Kathryn , Takeuchi Hirohito , Itoi Takao , Hasegawa Yasushi , Abe Yuta , Kitago Minoru , Ojima Hidenori , Sakamoto Michiie
Published: December 2024

Figure S9. Immune microenvironment of metastatic lesions reflects those of primary tumor in advanced HCC.
Supplementary Figure S1 from Spatial Dynamics of T- and B-Cell Responses Predicts Clinical Outcome of Resectable and Unresectable Hepatocellular Carcinoma
Authors: Kurebayashi Yutaka , Sugimoto Katsutoshi , Tsujikawa Hanako , Matsuda Kosuke , Nomura Rui , Ueno Akihisa , Masugi Yohei , Yamazaki Ken , Effendi Kathryn , Takeuchi Hirohito , Itoi Takao , Hasegawa Yasushi , Abe Yuta , Kitago Minoru , Ojima Hidenori , Sakamoto Michiie
Published: December 2024

Figure S1. TLS with or without GC formation.
Supplementary Table 3 from Reverse Selection Designs for Accommodating Multiple Control Arms
Authors: Samorodnitsky Sarah , Othus Megan , LeBlanc Michael , Wu Michael C.
Published: December 2024

Supplementary Table 3: Varying the true data generating model from the assumed model to test the effect on power and type I error rate.
Supplementary Data 1 from Reverse Selection Designs for Accommodating Multiple Control Arms
Authors: Samorodnitsky Sarah , Othus Megan , LeBlanc Michael , Wu Michael C.
Published: December 2024

Supplementary Data 1. Our supplementary materials contain additional simulation studies and an example.
Protocol 1 from Anlotinib plus TQB2450, a PD-L1 Antibody, in Patients with Advanced Alveolar Soft Part Sarcoma: A Single-Arm, Phase II Trial
Authors: Tan Zhichao , Wu Yan , Fan Zhengfu , Gao Tian , Guo Wei , Bai Chujie , Xue Ruifeng , Li Shu , Zhang Lu , Wang Xinyu , Jia Ling , Liu Jiayong
Published: December 2024

A Phase II clinical study to evaluate the safety and efficacy of TQB2450 injection combined with anlotinib hydrochloride capsule in patients with advanced soft tissue sarcoma: Protocol
Supplementary Table S2 from SWOG/NCI Phase II Dual Anti–CTLA-4/PD-1 Blockade in Rare Tumors: Nonepithelial Ovarian Cancer
Authors: Chae Young Kwang , Othus Megan , Patel Sandip Pravin , Wilkinson Kelly J. , Whitman-Purves Emily M. , Lea Jayanthi , Schallenkamp John M. , Adra Nabil , Appleman Leonard J. , Alden Mitchell , Thomes Pepin Jessica , Ellerton John A. , Poklepovic Andrew , Walter Adam , Rampurwala Murtuza M. , Robinson William R. , Kim Hye Sung , Chung Liam Il-Young , McLeod Christine M. , Lopez Gabby , Chen Helen X. , Sharon Elad , Streicher Howard , Ryan Christopher W. , Blanke Charles D. , Kurzrock Razelle
Published: December 2024

Representativeness of Study Participants
Table 1 from First-in-Human Dose-Escalation Study of Fianlimab, an Antilymphocyte Activation Gene-3 Antibody, with Cemiplimab in Patients with Advanced Malignancies
Authors: Lakhani Nehal J. , Papadopoulos Kyriakos P. , Johnson Melissa Lynne , Park Haeseong , Wang Ding , Yap Timothy A. , Dowlati Afshin , Maki Robert G. , Ulahannan Susanna , Lynce Filipa , Kelly Karen , Williamson Stephen , Malhotra Jyoti , Chen Shuquan , Gonzalez Ortiz Ana , Jankovic Vladimir , Paccaly Anne , Masinde Sheila , Mani Jayakumar , Lowy Israel , Gullo Giuseppe , Sims Tasha , Kroog Glenn
Published: December 2024

Baseline characteristics and prior therapies.
Table 1 from Circulating Chromogranin A as a Surveillance Biomarker in Patients with Carcinoids—The CASPAR Study
Authors: Meng Qing H. , Halfdanarson Thorvardur R. , Bornhorst Joshua A. , Jann Henning , Shaheen Shagufta , Shi Run Zhang , Schwabe Andrej , Stade Katrin , Halperin Daniel M.
Published: December 2024

Patient characteristics at baseline.
Supplementary Table S4 from Efficacy, Safety, and Influence on the Tumor Microenvironment of Neoadjuvant Pembrolizumab plus Ramucirumab for PD-L1–Positive NSCLC: A Phase II Trial (EAST ENERGY)
Authors: Aokage Keiju , Koyama Shohei , Kumagai Shogo , Nomura Kotaro , Shimada Yoshihisa , Yoh Kiyotaka , Wakabayashi Masashi , Fukutani Miki , Furuya Hideki , Miyoshi Tomohiro , Tane Kenta , Samejima Joji , Taki Tetsuro , Hayashi Takuo , Matsubayashi Jun , Ishii Genichiro , Nishikawa Hiroyoshi , Ikeda Norihiko , Tsuboi Masahiro
Published: December 2024

Supplementary Table S4: The frequency of worst surgery-related adverse events up to 90 days after surgery as graded by CTCAE v5.0.
Supplementary Table S3 from Efficacy, Safety, and Influence on the Tumor Microenvironment of Neoadjuvant Pembrolizumab plus Ramucirumab for PD-L1–Positive NSCLC: A Phase II Trial (EAST ENERGY)
Authors: Aokage Keiju , Koyama Shohei , Kumagai Shogo , Nomura Kotaro , Shimada Yoshihisa , Yoh Kiyotaka , Wakabayashi Masashi , Fukutani Miki , Furuya Hideki , Miyoshi Tomohiro , Tane Kenta , Samejima Joji , Taki Tetsuro , Hayashi Takuo , Matsubayashi Jun , Ishii Genichiro , Nishikawa Hiroyoshi , Ikeda Norihiko , Tsuboi Masahiro
Published: December 2024

Supplementary Table S3: Site of first recurrence in recurrent patients.
Supplementary Figure S1 from Efficacy, Safety, and Influence on the Tumor Microenvironment of Neoadjuvant Pembrolizumab plus Ramucirumab for PD-L1–Positive NSCLC: A Phase II Trial (EAST ENERGY)
Authors: Aokage Keiju , Koyama Shohei , Kumagai Shogo , Nomura Kotaro , Shimada Yoshihisa , Yoh Kiyotaka , Wakabayashi Masashi , Fukutani Miki , Furuya Hideki , Miyoshi Tomohiro , Tane Kenta , Samejima Joji , Taki Tetsuro , Hayashi Takuo , Matsubayashi Jun , Ishii Genichiro , Nishikawa Hiroyoshi , Ikeda Norihiko , Tsuboi Masahiro
Published: December 2024

Supplementary Figure S1: Sankey chart showing the relationship between pretreatment TNM classification and pathological TNM classification.
Data from Histology-Specific Clinical Trial of Lenvatinib and Pembrolizumab in Patients with Sarcoma
Authors: Movva Sujana , Seier Kenneth , Avutu Viswatej , Banks Lauren B. , Chan Jason , Chi Ping , Dickson Mark A. , Gounder Mrinal M. , Kelly Ciara M. , Keohan Mary L. , Maki Robert , Rosenbaum Evan , Salcito Tiffany , Rodriguez Kaithleen , Dempsey Rebecca , Meyers Paul A. , Cohen Seth M. , Hensley Martee L. , Konner Jason A. , Schram Alison M. , Lefkowitz Robert A. , Erinjeri Joseph P. , Qin Li-Xuan , Tap William D. , D’Angelo Sandra P.
Published: December 2024

AbstractPurpose:
Survival of patients with metastatic sarcoma remains poor, and there is a pressing need for new therapies. Most sarcoma subtypes are not responsive to immune checkpoint inhibition alone. Lenvatinib, a multireceptor tyrosine kinase inhibitor targeting tumor vasculature, has an immunomodulatory activity that contributes to its antitumor effects. Therefore, we hypothesized that a combination of lenvatinib and pembrolizumab would lead to improved clinical outcomes in patients with sarcoma.
Patients and Methods:
This was an open-label, single-arm study of lenvatinib and pembrolizumab in the following cohorts: (A) leiomyosarcoma, (B) undifferentiated pleomorphic sarcoma (UPS), (C) vascular sarcomas (angiosarcoma and epithelioid hemangioendothelioma), (D) synovial sarcoma or malignant peripheral nerve sheath tumor (MPNST), and (E) bone sarcomas (osteosarcoma and chondrosarcoma). The primary endpoint was the best overall response (BOR) rate documented by RECIST v1.1 by 27 weeks in each cohort, with a threshold of ≥2 responses among 10 patients. Secondary endpoints included progression-free survival, overall survival, duration of response, and safety.
Results:
Forty-six patients were evaluable for the primary endpoint, which was met in the UPS and MPNST/synovial cohorts (BOR rates by 27 weeks of 25% and 30%, respectively). There were seven partial responses overall with additional responses noted in angiosarcoma and osteosarcoma. Treatment-related adverse events of any grade and grade 3 or higher occurred in 50/51 (98%) and 29/51 (57%) of patients, respectively.
Conclusions:
We observed durable responses in MPNST, synovial sarcoma, and osteosarcoma. Patients with UPS and angiosarcoma also responded. Further exploration of this approach is warranted to confirm activity and determine optimal dosing schedules.
Data from Phase Ib Study of the Immunocytokine Simlukafusp Alfa (FAP-IL2v) in Combination with Cetuximab in Patients with Head and Neck Squamous Cell Carcinoma
Authors: Hansen Aaron R. , Gomez-Roca Carlos A. , Robbrecht Debbie G. J. , Verlingue Loic , Italiano Antoine , Bauman Julie E. , Steeghs Neeltje , Prenen Hans , Fayette Jérôme , Spicer James , Niu Jiaxin , Habigt Christin , Schneider Meike , Evers Stefan , Sleiman Nassim , Dejardin David , Ardeshir Caroline , Schmid Daniela , Boetsch Christophe , Charo Jehad , Kraxner Anton , Teichgräber Volker , Keshelava Nino , Bonomi Marcelo R.
Published: December 2024

Abstract
Purpose: This phase Ib trial evaluated fibroblast activation protein-α–targeted IL2 variant (FAP-IL2v), a novel immunocytokine engineered to minimize CD25-mediated toxicities, in combination with cetuximab, in patients with recurrent, unresectable, or metastatic head and neck squamous cell carcinoma (HNSCC).

Patients and Methods: Patients received FAP-IL2v either on a continuous weekly (QW) schedule or QW for 4 weeks and then every 2 weeks (Q2W). Cetuximab was dosed at QW or Q2W schedules. The primary objectives were to evaluate the safety and tolerability, maximum tolerated dose, pharmacokinetics, and clinical activity for the combination of FAP-IL2v with cetuximab. Exploratory objectives included pharmacodynamic analyses.

Results: A total of 58 patients were enrolled, 19 patients into the dose-escalation part, and 39 patients into the expansion part. The maximum tolerated dose of FAP-IL2v was defined as 10 mg (QW/Q2W) in combination with cetuximab (500 mg/m2, Q2W), which was further tested in the expansion part. The most common FAP-IL2v–related adverse events with a grade 3 or 4 severity were hypophosphatemia (19%), lymphopenia (16%), and infusion-related reaction (14%). The pharmacokinetics of FAP-IL2v in combination with cetuximab was similar to that after administration as monotherapy. Consistent with the proposed mode of action, FAP-IL2v preferentially expanded intratumoral NK and CD8 T cells. Four patients achieved a partial response, and the objective response rate was 7% (95% confidence interval, 3.2–14.7).

Conclusions: The safety profile of FAP-IL2v in combination with cetuximab was acceptable, and pharmacodynamic markers support the proposed mode of action of this combination, but the overall low antitumor activity does not warrant further clinical exploration in HNSCC. [Part C of Study BP29842 (NCT02627274).]
Data from Circulating Chromogranin A as a Surveillance Biomarker in Patients with Carcinoids—The CASPAR Study
Authors: Meng Qing H. , Halfdanarson Thorvardur R. , Bornhorst Joshua A. , Jann Henning , Shaheen Shagufta , Shi Run Zhang , Schwabe Andrej , Stade Katrin , Halperin Daniel M.
Published: December 2024

AbstractPurpose:
Gastroenteropancreatic neuroendocrine tumors (GEP-NET) are relatively indolent but can be more aggressive. The current recommendations for using serum chromogranin A (CgA) for patients with GEP-NET are equivocal. This study was designed to validate an automated CgA immunofluorescence assay for monitoring disease progression in patients with GEP-NET.
Patients and Methods:
A prospective, multicenter, blinded observational study was designed to validate an automated CgA immunofluorescence assay for monitoring disease progression in patients with GEP-NET. Tumor progression was evaluated with RECIST 1.1 by CT/MRI. An increase ≥50% above the prior CgA concentration to a value >100 ng/mL in the following CgA concentration was considered positive.
Results:
A total of 153 patients with GEP-NET were enrolled. Using the prespecified cut-off of CgA change for tumor progression, specificity was 93.4% (95% confidence interval, 90.4%–95.5%; P < 0.001), sensitivity 34.4% (25.6%–44.3%), positive predictive value 57.9% (45.0–69.8), negative predictive value 84.3% (80.5–87.6), and AUC 0.73 (0.67–0.79).
Conclusions:
Changes in serial measurements of serum CgA had a favorable specificity and negative predictive value, making this test a useful adjunct to routine radiographic monitoring.
Data from Genotype-Directed Synthetic Cytotoxicity of ATR Inhibition with Radiotherapy
Authors: Ng Victor , Sinha Sonali , Novaj Ardijana , Ma Jennifer , McDermott Niamh , Pei Xin , Longhini Ana Leda F. , Grimsley Helen , Gardner Rui , Rosen Ezra , Powell Simon N. , Pareja Fresia , Mandelker Diana , Khan Atif , Setton Jeremy , Roulston Anne , Morris Stephen , Koehler Maria , Lee Nancy , Reis-Filho Jorge , Riaz Nadeem
Published: December 2024

AbstractPurpose:
The importance of the DNA damage response in mediating effects of radiotherapy (RT) has galvanized efforts to target this pathway with radiosensitizers. Yet early clinical trials of this approach have failed to yield a benefit in unselected populations. We hypothesized that ataxia–telangiectasia mutated (Atm)–null tumors would demonstrate genotype-specific synergy between RT and an inhibitor of the DNA damage response protein ataxia–telangiectasia and Rad3-related (ATR) kinase.
Experimental Design:
We investigated the synergistic potential of the ATR inhibitor (ATRi) RP-3500 and RT in two Atm-null and isogenic murine models, both in vitro and in vivo. Staining of γ-H2AX foci, characterization of the immune response via flow cytometry, and tumor rechallenge experiments were performed to elucidate the mechanism of interaction. To examine genotype specificity, we tested the interaction of ATRi and RT in a Brca1-null model. Finally, patients with advanced cancer with ATM alterations were enrolled in a phase I/II clinical trial to validate preclinical findings.
Results:
Synergy between RP-3500 and RT was confirmed in Atm-null lines in vitro, characterized by an accumulation of DNA double-strand breaks. In vivo, Atm-null tumor models had higher rates of durable control with RT and ATRi than controls. In contrast, there was no synergy in tumors lacking Brca1. Analysis of the immunologic response indicated that efficacy is largely mediated by cell-intrinsic mechanisms. Lastly, early results from our clinical trial showed complete responses in patients.
Conclusions:
Genotype-directed radiosensitization with ATRi and RT can unleash significant therapeutic benefit and could represent a novel approach to develop more effective combinatorial synthetic cytotoxic RT-based treatments.

See related commentary by Schrank and Colbert, p. 5505
Sex Differences in Patients with Stroke: A Hospital-Based Multicenter Prospective Study in Brazil
Authors: Silva Gisele Sampaio , Rodrigues Daniela Laranja Gomes , Alves Monique Bueno , Miranda Renata Carolina Acri Nunes , Viana Georgiana Alvares Andrade , Santos Bento Fortunato Cardoso dos , Machado Cícera Borges , Lottenberg Claudio Luiz , Neto Miguel Cendoroglo , Tanjoni Renato , de Carvalho João José Freitas
Published: December 2024

Introduction: Stroke in Brazil disproportionately affects women, despite men having higher age-adjusted incidence and mortality rates. Women’s longer lifespan contributes to their increased stroke burden, particularly among older individuals. Objective: This study examines sex disparities in stroke epidemiology and treatment in Fortaleza, Brazil, addressing the lack of sex-specific stroke data. Methods: Data were prospectively collected from 19 hospitals between April 2009 and April 2012, following the WHO's Stroke Steps program, with analysis stratified by sex assigned at birth. Results: Out of 4,679 patients, 2,403 were females. Women were significantly older than men (69.1 years vs. 66.2 years, p < 0.01). Time to hospital admission and CT scans from symptom onset were similar between sexes. Men typically presented with motor, speech, and sensory symptoms, while women more often experienced decreased consciousness and headaches. Women had higher rates of diabetes and obesity, whereas men were more likely to smoke and have a history of alcohol abuse, myocardial infarctions, or strokes. Univariable logistic regressions examined factors affecting the modified Rankin Scale (mRS) scores at discharge, categorizing scores into 0-2 (lesser disability) and 3-6 (greater disability). Fewer women achieved an mRS score of ≤2 compared to men (77.6% vs. 81.7%, p < 0.01). Multivariable analysis indicated that being female increased the likelihood of a higher mRS score at discharge (OR 1.23, 95% CI [1.01-1.51], p = 0.04). Conclusion: The study highlights the persistent challenge for women in regaining independence post-stroke, emphasizing the need for personalized stroke care that addresses sex-specific differences.