bluuebunny/crossref_metadata_2025 huggingface dataset:
Thermal Performance and Technoeconomic Analysis of Solar-Assisted Heat Pump Dryer Integrated with Energy Storage Materials for Drying Cavendish Banana (Musa acuminata)
Authors: Loemba Aldé Belgard Tchicaya , Kichonge Baraka , Kivevele Thomas
Published: February 2024

This study examines a novel solar-assisted heat pump dryer integrated with a thermal energy storage system using soapstone as storage material. The dryer is investigated through experimental analysis across three operating modes: mode 1 with thermal energy storage during daytime, mode 2 without thermal energy storage during nighttime, and mode 3 without thermal energy storage during daytime. Experiments were carried out to investigate the drying of 500 g of Cavendish banana. Thermal performance, as well as economic, and nutritional content were examined. Three replicates of the experiment yielded consistent results, showing a significant reduction in the moisture content of the initial sample from 74.4% to 9.6% after undergoing distinct drying durations. Mode 1 achieved this reduction in 270 minutes, mode 2 in 390 minutes, and mode 3 in 360 minutes. The average specific moisture extraction rates for modes 1, 2, and 3 were 0.13, 0.11, and 0.12 kg/kWh, respectively. Simultaneously, the drying rate ranged from 0.16 to 0.24% per minute. The drying efficiency varied among the tested modes, with mode 1 achieving the highest efficiency at 23.23%. In terms of coefficient of performance, mode 1, mode 2, and mode 3 exhibited values of 3.69, 2.57, and 2.54, respectively. The economic analysis conducted specifically for mode 1 revealed a payback period of 1.5 years, indicating the time required to recover the initial investment. Additionally, the results indicated that the dried Cavendish banana had significantly higher concentrations of proximate parameters and minerals compared to the fresh Cavendish banana, as evidenced by a p value less than 0.05.
Effect of Fermentation Conditions (Dilution Ratio, Medium pH, Total Soluble Solids, and Saccharomyces cerevisiae Yeast Ratio) on the Ability to Ferment Cider from Tamarillo (Solanum betaceum) Fruit
Authors: Thuy Cao Xuan , Pham Van Thinh , Nguyen Trinh Thi Nhu Hang , Nguyen Thi Tuyet Ngan , Ton Nu Thuy An , Tuu Tran Thi , Vu Ngoc Duc
Published: February 2024

Tamarillo (Solanum betaceum) is a nutrition-rich product containing antioxidant components and preventive properties against cancer risk. However, there is currently a scarcity of research on processing techniques to diversify products and extend the preservation time of the active compounds in tamarillo. In this study, we focused on developing a cider processing procedure from tamarillo by fermentation with Saccharomyces cerevisiae (Angel RV002). Fermentation conditions, such as the dilution ratio (66 : 34–34 : 66%, w/w), medium pH (3.5–5), total soluble solids (TSS 10–26°Brix), and yeast ratio (0.6–1.2 g/L) were investigated. Ethanol concentration, pH, TSS, titratable acidity, total sugar content, and reducing sugar content were evaluated from day 0 to day 5 of fermentation. At a 50 : 50 (%, w/w) dilution ratio of the tamarillo juice with water, pH 4.5, TSS of 22°Brix, and the addition of yeast 0.6 g/L to the fermentation process, the ethanol concentration reached 7.54±0.11 (%, v/v) after 4 days of fermentation. Additionally, the product maintained a moderately low pH (pH 4.16). The final product exhibited a high sugar content and dissolved nutrients. The results of this study are expected to serve as a basis for the production of tamarillo cider, contributing to the diversification of the product, enhancing the value of tamarillo, and promoting economic development in the region of cultivation.
Strategies for Oxygen Ecosystems in Middle-Income Countries: A Review and Case Study from Lebanon
Authors: Baker Tim , Gatti Claudio , Rossini Guido , Tolla Habtamu , Detjen Anne , Mideksa Mulugeta , Hilal Nadeen , Shaya Rima
Published: February 2024

The COVID-19 pandemic led to a surge of critically ill patients and a sudden increase in the need for oxygen treatment worldwide. Pre-existing gaps in oxygen systems became apparent, and governments, multilateral agencies, and other partners scrambled to increase the production, supply, and use of oxygen to meet this need. The importance of an oxygen ecosystem that is appropriate for the local context became clear. This review describes strategies for oxygen ecosystems in middle-income countries, with specific experiences from Lebanon, following the authors’ extensive assessment of the country’s oxygen ecosystem, on behalf of the government and UNICEF. In the assessment, fifteen governmental hospitals were visited and evaluated using the UNICEF Oxygen System Planning Tool, discussions were held with key stakeholders, and documents were reviewed. An optimal oxygen ecosystem needs to take into consideration the production of oxygen and delivery to facilities, the maintenance system within facilities, and the clinical use of oxygen. Lebanon, a lower-middle income country in the Middle East, is contending with an extensive economic crisis affecting the health system. Eighteen recommendations for strengthening the oxygen ecosystem in Lebanon that are relevant for other middle-income countries include the establishment of a National Oxygen Committee, installation of additional oxygen plants, strengthened systems for maintenance and electricity supply, increased production, procurement and supply chain resilience, improved training and human resources, the use of data collection and regular information to guide the ecosystem, and integration of oxygen into the rest of the health system.
Antibody–Drug Conjugates: Advancing from Magic Bullet to Biological Missile
Authors: Veneziani Ana C. , Sneha Suku , Oza Amit M.
Published: February 2024

Precision drug development is focusing on targeting tumor cell surface proteins for therapeutic delivery, maximizing biomarker identified on-target damage to the tumor while minimizing toxicity. A recent article demonstrated high expression of B7-H4 antigen on resistant ovarian cancer cells and described preclinical activity of B7-H4–directed antibody–drug conjugate.

See related article by Gitto et al., p. 1567
Supplemental Table 4 from Acceptability of Personalized Lung Cancer Screening Program Among Primary Care Providers
Authors: Resong Paul J. , Niu Jiangong , Duhon Gabrielle F. , Foxhall Lewis E. , Shete Sanjay , Volk Robert J. , Toumazis Iakovos
Published: February 2024

Supplemental Table 4 shows provider level of agreement between 3 different proposed uses of biomarkers for lung cancer screening: as an adjuvant to the current screening, as a standalone means of screening, or as a guide to uncertain findings to the current screening methods.
Supplementary Table S9 from High-Fat Diet Promotes Acute Promyelocytic Leukemia through PPARδ-Enhanced Self-renewal of Preleukemic Progenitors
Authors: Mazzarella Luca , Falvo Paolo , Adinolfi Marta , Tini Giulia , Gatti Elena , Piccioni Rossana , Bonetti Emanuele , Gavilán Elena , Valli Debora , Gruszka Alicja , Bodini Margherita , Gallo Barbara , Orecchioni Stefania , de Michele Giulia , Migliaccio Enrica , Duso Bruno A. , Roerink Sophie , Stratton Mike , Bertolini Francesco , Alcalay Myriam , Dellino Gaetano Ivan , Pelicci Pier Giuseppe
Published: February 2024

Supplementary Table S9: Transcription Factor binding motif enrichment in PPARd targets
Supplementary Figure S1 from High-Fat Diet Promotes Acute Promyelocytic Leukemia through PPARδ-Enhanced Self-renewal of Preleukemic Progenitors
Authors: Mazzarella Luca , Falvo Paolo , Adinolfi Marta , Tini Giulia , Gatti Elena , Piccioni Rossana , Bonetti Emanuele , Gavilán Elena , Valli Debora , Gruszka Alicja , Bodini Margherita , Gallo Barbara , Orecchioni Stefania , de Michele Giulia , Migliaccio Enrica , Duso Bruno A. , Roerink Sophie , Stratton Mike , Bertolini Francesco , Alcalay Myriam , Dellino Gaetano Ivan , Pelicci Pier Giuseppe
Published: February 2024

Supplementary Figure S1: TMB by BMI class and copy number analysis, related to figure 3
Data from Acceptability of Personalized Lung Cancer Screening Program Among Primary Care Providers
Authors: Resong Paul J. , Niu Jiangong , Duhon Gabrielle F. , Foxhall Lewis E. , Shete Sanjay , Volk Robert J. , Toumazis Iakovos
Published: February 2024

Abstract
Current lung cancer screening (LCS) guidelines rely on age and smoking history. Despite its benefit, only 5%–15% of eligible patients receive LCS. Personalized screening strategies select individuals based on their lung cancer risk and may increase LCS's effectiveness. We assess current LCS practices and the acceptability of personalized LCS among primary care providers (PCP) in Texas. We surveyed 32,983 Texas-based PCPs on an existing network (Protocol 2019-1257; PI: Dr. Shete) and 300 attendees of the 2022 Texas Academy of Family Physicians (TAFP) conference. We analyzed the responses by subgroups of interest. Using nonparametric bootstrap, we derived an enriched dataset to develop logistic regression models to understand current LCS practices and acceptability of personalized LCS. Response rates were 0.3% (n = 91) and 15% (n = 60) for the 2019–1257 and TAFP surveys, respectively. Most (84%) respondents regularly assess LCS in their practice. Half of the respondents were interested in adopting personalized LCS. The majority (66%) of respondents expressed concerns regarding time availability with the personalized LCS. Most respondents would use biomarkers as an adjunct to assess eligibility (58%), or to help guide indeterminate clinical findings (63%). There is a need to enhance the engagement of Texas-based PCPs in LCS. Most of the respondents expressed interest in personalized LCS. Time availability was the main concern related to personalized LCS. Findings from this project highlight the need for better education of Texas-based PCPs on the benefits of LCS, and the development of efficient decision tools to ensure successful implementation of personalized LCS.
Prevention Relevance:
Personalized LCS facilitated by a risk model and/or a biomarker test is proposed as an alternative to existing programs. Acceptability of personalized approach among PCPs is unknown. The goal of this study is to assess the acceptability of personalized LCS among PCPs.
Data from High-Fat Diet Promotes Acute Promyelocytic Leukemia through PPARδ-Enhanced Self-renewal of Preleukemic Progenitors
Authors: Mazzarella Luca , Falvo Paolo , Adinolfi Marta , Tini Giulia , Gatti Elena , Piccioni Rossana , Bonetti Emanuele , Gavilán Elena , Valli Debora , Gruszka Alicja , Bodini Margherita , Gallo Barbara , Orecchioni Stefania , de Michele Giulia , Migliaccio Enrica , Duso Bruno A. , Roerink Sophie , Stratton Mike , Bertolini Francesco , Alcalay Myriam , Dellino Gaetano Ivan , Pelicci Pier Giuseppe
Published: February 2024

Abstract
Risk and outcome of acute promyelocytic leukemia (APL) are particularly worsened in obese-overweight individuals, but the underlying molecular mechanism is unknown. In established mouse APL models (Ctsg-PML::RARA), we confirmed that obesity induced by high-fat diet (HFD) enhances leukemogenesis by increasing penetrance and shortening latency, providing an ideal model to investigate obesity-induced molecular events in the preleukemic phase. Surprisingly, despite increasing DNA damage in hematopoietic stem cells (HSC), HFD only minimally increased mutational load, with no relevant impact on known cancer-driving genes. HFD expanded and enhanced self-renewal of hematopoietic progenitor cells (HPC), with concomitant reduction in long-term HSCs. Importantly, linoleic acid, abundant in HFD, fully recapitulates the effect of HFD on the self-renewal of PML::RARA HPCs through activation of peroxisome proliferator-activated receptor delta, a central regulator of fatty acid metabolism. Our findings inform dietary/pharmacologic interventions to counteract obesity-associated cancers and suggest that nongenetic factors play a key role.
Prevention Relevance:
Our work informs interventions aimed at counteracting the cancer-promoting effect of obesity. On the basis of our study, individuals with a history of chronic obesity may still significantly reduce their risk by switching to a healthier lifestyle, a concept supported by evidence in solid tumors but not yet in hematologic malignancies.

See related Spotlight, p. 47
Supplementary Figure 6 from Single-Cell Transcriptomics Reveals the Heterogeneity of the Immune Landscape of IDH–Wild-Type High-Grade Gliomas
Authors: Ran Xiaojuan , Zheng Jian , Chen Linchao , Xia Zhen , Wang Yin , Sun Chengfang , Guo Chen , Lin Peng , Liu Fuyi , Wang Chun , Zhou Jianguo , Sun Chongran , Liu Qichang , Ma Jianzhu , Qin Zhiyong , Zhu Xiangdong , Xie Qi
Published: February 2024

Supplementary Figure 6
Supplementary Figure S2 from RALDH1 Inhibition Shows Immunotherapeutic Efficacy in Hepatocellular Carcinoma
Authors: Yu Pengfei , Cao Shuwen , Yang Shyh-Ming , Rai Ganesha , Martinez Natalia J. , Yasgar Adam , Zakharov Alexey V. , Simeonov Anton , Molina Arocho William A. , Lobel Graham P. , Mohei Hesham , Scott Alexis L. , Zhai Li , Furth Emma E. , Simon M. Celeste , Haldar Malay
Published: February 2024

Supplementary Figure 2
Figure S9 from M9657 Is a Bispecific Tumor-Targeted Anti-CD137 Agonist That Induces MSLN-Dependent Antitumor Immunity without Liver Inflammation
Authors: Xu Chunxiao , Zhou Xueyuan , Webb Lindsay , Yalavarthi Sireesha , Zheng Wenxin , Saha Somdutta , Schweickhardt Rene , Soloviev Maria , Jenkins Molly H. , Brandstetter Susanne , Belousova Natalya , Alimzhanov Marat , Rabinovich Brian , Deshpande Amit M. , Brewis Neil , Helming Laura
Published: February 2024

muMSLN was depleted in the EMT‑6‑ MSLN‑del cell line
Figure S6 from M9657 Is a Bispecific Tumor-Targeted Anti-CD137 Agonist That Induces MSLN-Dependent Antitumor Immunity without Liver Inflammation
Authors: Xu Chunxiao , Zhou Xueyuan , Webb Lindsay , Yalavarthi Sireesha , Zheng Wenxin , Saha Somdutta , Schweickhardt Rene , Soloviev Maria , Jenkins Molly H. , Brandstetter Susanne , Belousova Natalya , Alimzhanov Marat , Rabinovich Brian , Deshpande Amit M. , Brewis Neil , Helming Laura
Published: February 2024

M9657 treatment induces IFNγ and TNFα release in cell lines with varied MSLN expression.
Supplementary table 3 from Tumor-Derived RAB21+ABHD12+ sEVs Drive the Premetastatic Microenvironment in the Lung
Authors: Wu Kun , Li Yan , Ji Yikang , Liu Chun , Wang Xiaoning , Guo Haiyan , Zhang Jianjun , He Yue
Published: February 2024

Supplementary table 3
Figure S14 from M9657 Is a Bispecific Tumor-Targeted Anti-CD137 Agonist That Induces MSLN-Dependent Antitumor Immunity without Liver Inflammation
Authors: Xu Chunxiao , Zhou Xueyuan , Webb Lindsay , Yalavarthi Sireesha , Zheng Wenxin , Saha Somdutta , Schweickhardt Rene , Soloviev Maria , Jenkins Molly H. , Brandstetter Susanne , Belousova Natalya , Alimzhanov Marat , Rabinovich Brian , Deshpande Amit M. , Brewis Neil , Helming Laura
Published: February 2024

Schematic of M9657 mechanism of action
Figure S10 from M9657 Is a Bispecific Tumor-Targeted Anti-CD137 Agonist That Induces MSLN-Dependent Antitumor Immunity without Liver Inflammation
Authors: Xu Chunxiao , Zhou Xueyuan , Webb Lindsay , Yalavarthi Sireesha , Zheng Wenxin , Saha Somdutta , Schweickhardt Rene , Soloviev Maria , Jenkins Molly H. , Brandstetter Susanne , Belousova Natalya , Alimzhanov Marat , Rabinovich Brian , Deshpande Amit M. , Brewis Neil , Helming Laura
Published: February 2024

FS122m generates dose-dependent antitumor efficacy and long-term tumor antigen-specific immune protection.
Supplement figure 4 from Tumor-Derived RAB21+ABHD12+ sEVs Drive the Premetastatic Microenvironment in the Lung
Authors: Wu Kun , Li Yan , Ji Yikang , Liu Chun , Wang Xiaoning , Guo Haiyan , Zhang Jianjun , He Yue
Published: February 2024

Supplementary Figure 4. (a) Quantitative analysis for ABHD12 in sEVs from HNSCC cell lines (SCC25 and HN6). (b) Quantitative analysis for ABHD12 in macrophages. (c) Flow cytometry analysis for percentage of M2 macrophages (CD163+CD206+) in coculture system (25μg sEVs, 50μg sEVs and 75μg sEVs); (d-h) The 50μg sEVs (sEVsNC, sEVsABHD12-KD, sEVsABHD12-OE and sEVsRAB21-KD) derived from SCC7 were injected into tail vein. After 24 h, flow cytometry analysis for CD8+ T cells, Tregs (Foxp3+) and CD4+ T cells. (d) Percentage of CD8 T cells; (e) the PD-1 level of CD8 T cells; (f) Percentage of CD4 T cells; (g) The PD-1 level of CD4 T cells; (h) Percentage of Treg cells.
Supplementary video 2 from Engagement of CD99 Activates Distinct Programs in Ewing Sarcoma and Macrophages
Authors: Manara Maria Cristina , Manferdini Cristina , Cristalli Camilla , Carrabotta Marianna , Santi Spartaco , De Feo Alessandra , Caldoni Giulia , Pasello Michela , Landuzzi Lorena , Lollini Pier-Luigi , Salamanna Francesca , Dominici Sabrina , Fiori Valentina , Magnani Mauro , Lisignoli Gina , Scotlandi Katia
Published: February 2024

Video 2 12E7
Supplementary video 1 from Engagement of CD99 Activates Distinct Programs in Ewing Sarcoma and Macrophages
Authors: Manara Maria Cristina , Manferdini Cristina , Cristalli Camilla , Carrabotta Marianna , Santi Spartaco , De Feo Alessandra , Caldoni Giulia , Pasello Michela , Landuzzi Lorena , Lollini Pier-Luigi , Salamanna Francesca , Dominici Sabrina , Fiori Valentina , Magnani Mauro , Lisignoli Gina , Scotlandi Katia
Published: February 2024

Video 1 CTRL
Supplementary Figure 2 from Immune Modulation of Innate and Adaptive Responses Restores Immune Surveillance and Establishes Antitumor Immunologic Memory
Authors: Alvero Ayesha B. , Fox Alexandra , Madina Bhaskara Reddy , Krady Marie M. , Gogoi Radhika , Chehade Hussein , Nakaar Valerian , Almassian Bijan , Yarovinsky Timur O. , Rutherford Thomas , Mor Gil
Published: February 2024

Diagram showing major immune phenotypes in each phase of ovarian tumor progression.
Supplementary Figure 2 from Engagement of CD99 Activates Distinct Programs in Ewing Sarcoma and Macrophages
Authors: Manara Maria Cristina , Manferdini Cristina , Cristalli Camilla , Carrabotta Marianna , Santi Spartaco , De Feo Alessandra , Caldoni Giulia , Pasello Michela , Landuzzi Lorena , Lollini Pier-Luigi , Salamanna Francesca , Dominici Sabrina , Fiori Valentina , Magnani Mauro , Lisignoli Gina , Scotlandi Katia
Published: February 2024

Supplementary Figure 2
Data from Single-Cell Transcriptomics Reveals the Heterogeneity of the Immune Landscape of IDH–Wild-Type High-Grade Gliomas
Authors: Ran Xiaojuan , Zheng Jian , Chen Linchao , Xia Zhen , Wang Yin , Sun Chengfang , Guo Chen , Lin Peng , Liu Fuyi , Wang Chun , Zhou Jianguo , Sun Chongran , Liu Qichang , Ma Jianzhu , Qin Zhiyong , Zhu Xiangdong , Xie Qi
Published: February 2024

Abstract
Isocitrate dehydrogenase (IDH)–wild-type (WT) high-grade gliomas, especially glioblastomas, are highly aggressive and have an immunosuppressive tumor microenvironment. Although tumor-infiltrating immune cells are known to play a critical role in glioma genesis, their heterogeneity and intercellular interactions remain poorly understood. In this study, we constructed a single-cell transcriptome landscape of immune cells from tumor tissue and matching peripheral blood mononuclear cells (PBMC) from IDH-WT high-grade glioma patients. Our analysis identified two subsets of tumor-associated macrophages (TAM) in tumors with the highest protumorigenesis signatures, highlighting their potential role in glioma progression. We also investigated the T-cell trajectory and identified the aryl hydrocarbon receptor (AHR) as a regulator of T-cell dysfunction, providing a potential target for glioma immunotherapy. We further demonstrated that knockout of AHR decreased chimeric antigen receptor (CAR) T-cell exhaustion and improved CAR T-cell antitumor efficacy both in vitro and in vivo. Finally, we explored intercellular communication mediated by ligand–receptor interactions within the tumor microenvironment and PBMCs and revealed the unique cellular interactions present in the tumor microenvironment. Taken together, our study provides a comprehensive immune landscape of IDH-WT high-grade gliomas and offers potential drug targets for glioma immunotherapy.
Data from RALDH1 Inhibition Shows Immunotherapeutic Efficacy in Hepatocellular Carcinoma
Authors: Yu Pengfei , Cao Shuwen , Yang Shyh-Ming , Rai Ganesha , Martinez Natalia J. , Yasgar Adam , Zakharov Alexey V. , Simeonov Anton , Molina Arocho William A. , Lobel Graham P. , Mohei Hesham , Scott Alexis L. , Zhai Li , Furth Emma E. , Simon M. Celeste , Haldar Malay
Published: February 2024

Abstract
Globally, hepatocellular carcinoma (HCC) is one of the most commonly diagnosed cancers and a leading cause of cancer-related death. We previously identified an immune evasion pathway whereby tumor cells produce retinoic acid (RA) to promote differentiation of intratumoral monocytes into protumor macrophages. Retinaldehyde dehydrogenase 1 (RALDH1), RALDH2, and RALDH3 are the three isozymes that catalyze RA biosynthesis. In this study, we have identified RALDH1 as the key driver of RA production in HCC and demonstrated the efficacy of RALDH1-selective inhibitors (Raldh1-INH) in suppressing RA production by HCC cells. Raldh1-INH restrained tumor growth in multiple mouse models of HCC by reducing the number and tumor-supporting functions of intratumoral macrophages as well as increasing T-cell infiltration and activation within tumors. Raldh1-INH also displayed favorable pharmacokinetic, pharmacodynamic, and toxicity profiles in mice thereby establishing them as promising new drug candidates for HCC immunotherapy.
Data from Tumor-Derived RAB21+ABHD12+ sEVs Drive the Premetastatic Microenvironment in the Lung
Authors: Wu Kun , Li Yan , Ji Yikang , Liu Chun , Wang Xiaoning , Guo Haiyan , Zhang Jianjun , He Yue
Published: February 2024

Abstract
Tumor metastasis is a spatial and temporal process that starts with remodeling to generate a proper premetastatic niche in a distant tissue. Infiltration of immunosuppressive macrophages is one of the notable characteristics in the premetastatic niche, which is a fundamental requirement for primary tumor metastasis. Here, we demonstrated that small extracellular vesicles (sEV) carrying RAB21 homed to lung macrophages and interacted with integrin-β1 on macrophages. ABHD12 expression was high in lung metastatic tumors and was mostly expressed by macrophages. Head and neck squamous cell carcinoma (HNSCC)–derived sEVs carrying ABHD12-polarized macrophages toward an immunosuppressive phenotype, driving premetastatic niche formation, which facilitated lung metastasis. ABHD12 additionally upregulated S1PR1 by activating the AKT–FoxO1 pathway in macrophages, and significantly enhanced antitumor responses were observed in tumor models treated with agents targeting both S1PR1 and PD-1. Collectively, our study suggests that RAB21+ABHD12+ sEVs derived from HNSCC cells contribute to the formation of the immunosuppressive microenvironment in the premetastatic niche and are a potential therapeutic target for enhancing the antitumor efficacy of anti–PD-1 therapy.
Data from Immune Modulation of Innate and Adaptive Responses Restores Immune Surveillance and Establishes Antitumor Immunologic Memory
Authors: Alvero Ayesha B. , Fox Alexandra , Madina Bhaskara Reddy , Krady Marie M. , Gogoi Radhika , Chehade Hussein , Nakaar Valerian , Almassian Bijan , Yarovinsky Timur O. , Rutherford Thomas , Mor Gil
Published: February 2024

Abstract
Current immunotherapies have proven effective in strengthening antitumor immune responses, but constant opposing signals from tumor cells and the surrounding microenvironment eventually lead to immune escape. We hypothesized that in situ release of antigens and regulation of both the innate and adaptive arms of the immune system would provide a robust and long-term antitumor effect by creating immunologic memory against tumors. To achieve this, we developed CARG-2020, a genetically modified virus-like vesicle (VLV) that is a self-amplifying RNA with oncolytic capacity and encodes immune regulatory genes. CARG-2020 carries three immune modulators: (i) the pleiotropic antitumor cytokine IL12, in which the subunits (p35 and p40) are tethered together; (ii) the extracellular domain (ECD) of the protumor IL17RA, which serves as a dominant-negative antagonist; and (iii) a shRNA targeting PD-L1. Using a mouse model of ovarian cancer, we demonstrated the oncolytic effect and immune-modulatory capacities of CARG-2020. By enhancing IL12 and blocking IL17 and PD-L1, CARG-2020 successfully reactivated immune surveillance by promoting M1, instead of M2, macrophage differentiation, inhibiting MDSC expansion and establishing a potent CD8+ T cell–mediated antitumoral response. Furthermore, we demonstrated that this therapeutic approach provided tumor-specific and long-term protection against the establishment of new tumors. Our results provide a rationale for the further development of this platform as a therapeutic modality for ovarian cancer patients to enhance antitumor responses and prevent a recurrence.
Supplementary Figure S5 from Aberrant Upregulation of RUNX3 Activates Developmental Genes to Drive Metastasis in Gastric Cancer
Authors: Suda Kazuto , Okabe Atsushi , Matsuo Junichi , Chuang Linda Shyue Huey , Li Ying , Jangphattananont Nawaphat , Mon Naing Naing , Myint Khine Nyein , Yamamura Akihiro , So Jimmy Bok-Yan , Voon Dominic Chih-Cheng , Yang Henry , Yeoh Khay Guan , Kaneda Atsushi , Ito Yoshiaki
Published: February 2024

Addition of exogenous recombinant WNT5A restores migration and invasion abilities to RUNX3 KO cells A, WST-1 cell proliferation assay in HGC-27 after siRNA mediated WNT5A KD; *, P < 0.05 by a two-tailed Student t test. B, immunoblot for WNT5A in HGC-27 KO cells after WNT5A recombinant treatment (0.1mg/mL) is shown. C, representative images for HGC-27 and LMSU after siWNT5A, and in GAS24 after WNT5A recombinant treatment (0.1mg/mL) in Matrigel colony formation assay (top). The number of colony formation was counted and shown as a fold change to control cells (mean + SD); **, P < 0.01 and *, P < 0.05 by a two-tailed Student t test.
Prevalence, Risk Factors, and Interventions of Postpartum Depression in Refugees and Asylum-Seeking Women: A Systematic Review and Meta-Analysis
Authors: Heer Karnvir , Mahmoud Lujayn , Abdelmeguid Hana , Selvan Kavin , Malvankar-Mehta Monali S.
Published: February 2024

Introduction: Refugee women are at an increased risk of developing postpartum depression (PPD) due to a combination of various psychosocial stressors. This systematic review aimed to outline the prevalence of PPD among refugee women and explore related risk factors and interventions currently in practice. Methods: A search was conducted using MEDLINE, Embase, PsycINFO, CINAHL, and Core Collection (Web of Science) for articles published until August 2022, yielding 1,678 records. Results: The prevalence of refugee and asylum-seeking women was 22.5% (n = 657/2,922), while the prevalence of non-refugee/asylum-seeking women with PPD was 17.5% (n = 400/2,285). Refugee/asylum-seeking women face a unique set of issues such as domestic abuse, separation and lack of support, stress, pre-migrational experiences, prior history of mental illness, low income, and discrimination. Refugee/asylum-seeking women may benefit from support groups, individual support, self-coping mechanisms, and familial support. Conclusion: This review identifies that a higher prevalence of PPD in refugee and asylum-seeking women compared to other groups can potentially be attributed to the unique risk factors they face. This warrants the need for further research as studies on interventions for this condition are limited among this population.
Risiko venöser Thromboembolien bei Autoimmunerkrankungen: Eine umfassende Übersicht
Authors: Menichelli Danilo , Cormaci Vito Maria , Marucci Silvia , Franchino Giovanni , Del Sole Francesco , Capozza Alessandro , Fallarino Alessia , Valeriani Emanuele , Violi Francesco , Pignatelli Pasquale , Pastori Daniele
Published: February 2024

Autoimmunerkrankungen haben spezifische pathophysiologische Mechanismen, die zu einem erhöhten Risiko für arterielle und venöse Thrombosen führen. Das Risiko einer venösen Thromboembolie (VTE) variiert je nach Art und Stadium der Erkrankung sowie der begleitenden Therapie. In dieser Übersichtsarbeit werden die häufigsten Autoimmunerkrankungen wie Anti-Phospholipid-Syndrom, entzündliche Myositis, Polymyositis und Dermatomyositis, rheumatoide Arthritis, Sarkoidose, Sjögren-Syndrom, autoimmunhämolytische Anämie, systemischer Lupus erythematodes, systemische Sklerose, Vaskulitis und chronisch-entzündliche Darmerkrankungen behandelt. Darüber hinaus geben wir einen Überblick über die Pathophysiologie, die für das VTE-Risiko bei jeder Autoimmunerkrankung verantwortlich ist, und berichten über die aktuellen Indikationen für eine gerinnungshemmende Therapie zur Primär- und Sekundärprävention von VTE.
ES-SCLC: Kombinierte Immunchemotherapie ist effektiv und sicher
Authors: Schumann Christian
Published: February 2024

Background: Immunotherapy in combination with platinum-etoposide (EP) chemotherapy has been approved as a first-line treatment for extensive-stage small cell lung cancer (ES-SCLC). However, real-world (RW) data regarding the use of immune checkpoint inhibitors (ICIs) in ES-SCLC are lacking. We aimed to assess the differences between programmed death protein 1 (PD-1) inhibitors and programmed death ligand 1 (PD-L1) inhibitors, both in conjunction with EP chemotherapy, as first-line treatment for ES SCLC. Methods: We conducted a real-world, multicenter, retrospective cohort, controlled study to compare the prognosis, efficacy, and safety of PD-1 and PD-L1 inhibitors in ES-SCLC patients when used along with chemotherapy. Each patient received up to six cycles of etoposide, carboplatin, or cisplatin combined with ICI drugs, including PD-1 and PD-L1 inhibitors. The primary endpoints were investigator-assessed progression-free survival (PFS) and overall survival (OS). The secondary endpoints were the investigator-assessed objective response rate (ORR) and disease control rate (DCR) according to the Response Evaluation Criteria in Solid Tumors (RECIST, version 1.1). Results: Between January 2017 and December 2021, 194 patients with ES-SCLC from three clinical centers in a PLA general hospital were included in our study, including 93 patients in the PD-1 group and 101 patients in the PD-L1 group. At the time of data cutoff, progression-free survival in the PD-1 group (median PFS, 6.8 months; 95% CI, 5.3–8.1 was similar to that in the PD-L1 group (median PFS, 6.4 months; 95% CI, 5.5–7.5); the stratified hazard ratio for PFS was 1.12 (95% CI, 0.83–1.53; P = 0.452). The median OS was similar in the PD-1 and PD-L1 groups (15.8 m vs. 17.7 m, P = 0.566); the hazard ratio was 0.90 (95% CI, 0.62–1.30, P = 0.566). The two groups had comparable investigator-assessed confirmed objective response rates (ORR) (76.3% vs. 76.2%). Adverse effect (AE)-related discontinuation occurred in 4 (4.3%) patients in the PD-1 group and 2 (2.0%) patients in the PD-L1 group. Deaths due to AEs of any cause occurred in 2 (2.2%) patients in the PD-1 inhibitor group and 1 (1.0%) patient in the PD-L1 inhibitor group.
Large-scale text analysis using generative language models: A case study in discovering public value expressions in AI patents
Authors: Pelaez Sergio , Verma Gaurav , Ribeiro Barbara , Shapira Philip
Published: February 2024

We put forward a novel approach using a generative language model (GPT-4) to produce labels and rationales for large-scale text analysis. The approach is used to discover public value expressions in patents. Using text (5.4 million sentences) for 154,934 US AI patent documents from the United States Patent and Trademark Office (USPTO), we design a semi-automated, human-supervised framework for identifying and labeling public value expressions in these sentences. A GPT-4 prompt is developed that includes definitions, guidelines, examples, and rationales for text classification. We evaluate the labels and rationales produced by GPT-4 using BLEU scores and topic modeling, finding that they are accurate, diverse, and faithful. GPT-4 achieved an advanced recognition of public value expressions from our framework, which it also uses to discover unseen public value expressions. The GPT-produced labels are used to train BERT-based classifiers and predict sentences on the entire database, achieving high F1 scores for the 3-class (0.85) and 2-class classification (0.91) tasks. We discuss the implications of our approach for conducting large-scale text analyses with complex and abstract concepts. With careful framework design and interactive human oversight, we suggest that generative language models can offer significant assistance in producing labels and rationales.
The Post-Ongwen Case Period and the Reconciliation Process in Northern Uganda: Local Communities as a Site of Knowledge
Authors: Molima Bameka Christelle
Published: February 2024

By providing victims with more space in the Ongwen case, the International Criminal Court (icc) has significantly contributed to the healing of the trauma and community reconciliation in northern Uganda. That said, this court has also raised issues that could affect local efforts to achieve peace, namely the positioning of victims of child soldiers vis-à-vis criminal child soldiers. Drawing on qualitative data collected through focus group discussions with some community members from locations under investigation by the icc, this sociolegal study examines the victims’ narratives about child soldiers and the different ideas of human rights that emerge. Then, it explores how these ideas may shape future transitional justice mechanisms designed in the global sphere. Finally, it discusses the extent to which they may impact the relevance of current justice initiatives. Overall, this paper analyzes the substantive effect of victim participation in the Ongwen case on local peacebuilding initiatives in northern Uganda.
Effect of stacking angles on crashworthiness of CFRP square tubes considering low-velocity impact damage
Authors: Yang Chenxi , Ren Yiru
Published: February 2024

To enhance the residual energy‐absorption (EA) of low-velocity impact-damaged CFRP square tubes, this study investigates the influence of stacking angles on the damaged tubes' residual EA. Through simulation and theoretical analysis, a well-designed stacking angles is proposed to optimize the residual EA. Initially, a simplified method of low-velocity impact damage of composite materials is proposed, by which a discontinuous damage mechanics finite element model is established and experimentally verified. Subsequently, various layup sequences are examined, and their impact on energy absorption is evaluated using several performance indices, including initial peak load, average load, energy absorption, specific energy absorption, and crushing load efficiency. The findings demonstrate that the designed stacking angles significantly enhances the residual energy absorption of low-velocity impact-damaged square tubes. Moreover, the study verifies the efficacy of the stacking angles design by investigating actual damage conditions, encompassing factors such as damage size, location, and stress concentration.
Defining and reporting exercise intensity in interventions for older adults: a modified Delphi process
Authors: Wollesen Bettina , Herden Mona , Lamberti Nicola , Giannaki Christoforos D.
Published: February 2024

Background

Many exercise studies, including older adults, do not report all relevant exercise characteristics. Especially the description of exercise intensity is missing and mostly not controlled. This leads to difficulties in interpreting study results and summarizing the evidence in systematic reviews or meta-analyses. Therefore, the aim of the present Delphi study was to gain recommendations about the categorization of exercise intensity and for the conducting and reporting of characteristics in future intervention studies with older adults by experts in exercise science and physiology.

Methods

Two hundred ninety-seven international interdisciplinary participants from an EU COST action were invited to participate in three rounds of online questionnaires in April/May 2023. Up to N = 93 experts participated in each round. Round 1 included open-ended questions to solicit possible recommendations and categorizations for light, moderate, vigorous, and high intensity. In round 2, the experts rated their agreement using Likert scales (1–10) on the revealed categories and recommendations. Clusters with a higher average rating of M = 8.0 were summarized into round 3. In the final round, the results were presented for a final rating of agreement (based on a simple majority > 50%).

Results

In round 1 a total of 416 qualitative statements were provided from thirteen questions. From round 1 to round 3, a total of 38 items were excluded, with 205 items retained for the final consensus. In round three 37 participants completed the whole questionnaire. The experts showed overall agreement on the final categorizations with 6.7 to 8.8 out of 10 points on the Likert scale. They also showed broad consensus on the relevance of reporting exercise intensity and the recommendations for future conducting and reporting of study results. However, exercise types such as yoga, balance, and coordination training led to conflicting results for categorization into light or moderate.

Discussion and implications

The results of the current survey can be used to classify the intensity of exercise and suggest a practical approach that can be adopted by the scientific community and applied when conducting systematic reviews and meta-analysis articles when vital and objective information regarding exercise intensity is lacking from the original article.
EV-share development: speed vs interest to adopt
Authors: Viri Riku , Mäkinen Johanna
Published: February 2024

Transport is a notable source of greenhouse gas emissions. While the mobility habits of people have an effect on a large share of the emissions, the development of the car fleet also plays a major role. In this study, Finnish SALAMA-model is used to calculate nine different scenarios, examining how changes in both the car fleet turnover speed and interest towards electric vehicles (EVs) affect the amount of EVs and total emissions from the passenger cars in Finland up to the year 2040. With the baseline scenario (normal interest and car fleet turnover speed) 28% of cars in use would be EVs (total of PHEVs and BEVs) by 2030. In contrast, scenario with higher interest and faster turnover suggest that nearly half of all cars could be EVs. When focusing on CO2 emissions, only the scenario with the fastest turnover speed with high interest aligns with the Finnish targets for 2030. Thus, car fleet development is only a part of the emission reduction, and other measures are also needed. Based on the results, it should be noted that even though many current and past policies are often focused on increasing interest towards EVs, any solutions driving faster turnover of the car fleet would also significantly impact emission reduction.
Ecological and phylogenetic aspects of the spring diet of three palaearctic species of swans
Authors: Kouzov Sergei A. , Kravchuk Anna V. , Koptseva Elena M. , Gubelit Yulia I. , Zaynagutdinova Elmira M. , Abakumov Evgeny V.
Published: February 2024

The quality of swans' nutrition at spring migration stopovers is important for their successful breeding. It is of great interest to study the differences in nutrition of different swan species when sharing the same habitat. Microscopic analysis of Cygnus olor, C. cygnus, and C. columbianus bewickii feces collected in the eastern part of the Gulf of Finland in February-April 2014–2019 was performed. We measured food preferences of the three swan species using non-metric multidimensional scaling (NMDS). The width and overlap of dietary niches were also calculated. The diet of C. olor consists almost entirely of soft submerged aquatic vegetation, mainly macroalgae. Samples of the other two species except macroalgae contained large amounts of young shoots and roots of rigid semi-submerged and coastal vegetation. The dietary niche of C. cygnus is the most isolated because it is dominated by thick rhizomes of Phragmites australis, which are hardly used by other swan species. The diet of Bewick’s swans was similar in many respects to that of the Mute swan, but Bewick’s swans much more often preferred vegetative parts of submerged and semi-submerged plants, such as Stuckenia pectinata, Potamogeton perfoliatus, Sparganium sp., Nuphar lutea, and others. Notably, the dietary niches of Mute swan and Whooper swan overlapped as much as possible in February March during a period of severe food shortage, in contrast to later periods in spring when food was more abundant and varied. In general, differences in diets are well explained by differences in the morphology of birds. Comparison of tarsometatarsus indices shows that C. olor is the most water-related species. C. olor has the longest neck and its beak has the strongest filter features, whereas beaks of the other two species shows noticeable “goose-like grazing” features. Moreover, C. Cygnus has the most powerful beak. These features are due to the history of species. The formation of C. olor occurred during the Miocene-Pliocene of the Palaearctic in the warm eutrophic marine lagoons of the Paratethys with abundant soft submerged vegetation. The evolution of C. cygnus and C. c. bewickii took place in Pleistocene. At that time, periglacial and thermokarst water bodies on permafrost became widespread in the Palearctic, as well as dystrophic peat lakes with much poorer submerged aquatic vegetation, but well-developed coastal and semi-submerged vegetation.
DendroX: multi-level multi-cluster selection in dendrograms
Authors: Feng Feiling , Duan Qiaonan , Jiang Xiaoqing , Kao Xiaoming , Zhang Dadong
Published: February 2024

Background

Cluster heatmaps are widely used in biology and other fields to uncover clustering patterns in data matrices. Most cluster heatmap packages provide utility functions to divide the dendrograms at a certain level to obtain clusters, but it is often difficult to locate the appropriate cut in the dendrogram to obtain the clusters seen in the heatmap or computed by a statistical method. Multiple cuts are required if the clusters locate at different levels in the dendrogram.

Results

We developed DendroX, a web app that provides interactive visualization of a dendrogram where users can divide the dendrogram at any level and in any number of clusters and pass the labels of the identified clusters for functional analysis. Helper functions are provided to extract linkage matrices from cluster heatmap objects in R or Python to serve as input to the app. A graphic user interface was also developed to help prepare input files for DendroX from data matrices stored in delimited text files. The app is scalable and has been tested on dendrograms with tens of thousands of leaf nodes. As a case study, we clustered the gene expression signatures of 297 bioactive chemical compounds in the LINCS L1000 dataset and visualized them in DendroX. Seventeen biologically meaningful clusters were identified based on the structure of the dendrogram and the expression patterns in the heatmap. We found that one of the clusters consisting of mostly naturally occurring compounds is not previously reported and has its members sharing broad anticancer, anti-inflammatory and antioxidant activities.

Conclusions

DendroX solves the problem of matching visually and computationally determined clusters in a cluster heatmap and helps users navigate among different parts of a dendrogram. The identification of a cluster of naturally occurring compounds with shared bioactivities implicates a convergence of biological effects through divergent mechanisms.
Tmem119 expression is downregulated in a subset of brain metastasis-associated microglia
Authors: Ma Weili , Oswald Jack , Rios Angulo Angela , Chen Qing
Published: February 2024

Under pathological conditions, the immune-specialized brain microenvironment contains both resident microglia and bone marrow-derived myeloid cells recruited from peripheral circulation. Due to largely overlapping phenotypic similarities between these ontogenically distinct myeloid populations, studying their individual functions in central nervous system diseases has been challenging. Recently, transmembrane protein 119 (Tmem119) has been reported as a marker for resident microglia which is not expressed by bone marrow-derived myeloid cells. However, several studies have reported the loss or reduction of Tmem119 expression in pathologically activated microglia. Here, we examined whether Tmem119 could be used as a robust marker to identify brain metastasis-associated microglia. In addition, we also compared Tmem119 expression of primary microglia to the immortalized microglia-like BV2 cell line and characterized expression changes after LPS treatment. Lastly, we used a commercially available transgenic mouse line (Tmem119-eGFP) to compare Tmem119 expression patterns to the traditional antibody-based detection methods. Our results indicate that brain metastasis-associated microglia have reduced Tmem119 gene and protein expression.
Dietary intervention reverses molecular markers of hepatocellular senescence in the GAN diet-induced obese and biopsy-confirmed mouse model of NASH
Authors: Flensted-Jensen Mathias , Oró Denise , Rørbeck Emma A. , Zhang Chen , Madsen Martin Rønn , Madsen Andreas Nygaard , Norlin Jenny , Feigh Michael , Larsen Steen , Hansen Henrik H.
Published: February 2024

Background

Hepatocellular senescence may be a causal factor in the development and progression of non-alcoholic steatohepatitis (NASH). The most effective currently available treatment for NASH is lifestyle intervention, including dietary modification. This study aimed to evaluate the effects of dietary intervention on hallmarks of NASH and molecular signatures of hepatocellular senescence in the Gubra-Amylin NASH (GAN) diet-induced obese (DIO) and biopsy-confirmed mouse model of NASH.

Methods

GAN DIO-NASH mice with liver biopsy-confirmed NASH and fibrosis received dietary intervention by switching to chow feeding (chow reversal) for 8, 16 or 24 weeks. Untreated GAN DIO-NASH mice and chow-fed C57BL/6J mice served as controls. Pre-to-post liver biopsy histology was performed for within-subject evaluation of NAFLD Activity Score and fibrosis stage. Terminal endpoints included blood/liver biochemistry, quantitative liver histology, mitochondrial respiration and RNA sequencing.

Results

Chow-reversal promoted substantial benefits on metabolic outcomes and liver histology, as demonstrated by robust weight loss, complete resolution of hepatomegaly, hypercholesterolemia, elevated transaminase levels and hepatic steatosis in addition to attenuation of inflammatory markers. Notably, all DIO-NASH mice demonstrated ≥ 2 point significant improvement in NAFLD Activity Score following dietary intervention. While not improving fibrosis stage, chow-reversal reduced quantitative fibrosis markers (PSR, collagen 1a1, α-SMA), concurrent with improved liver mitochondrial respiration, complete reversal of p21 overexpression, lowered γ-H2AX levels and widespread suppression of gene expression markers of hepatocellular senescence.

Conclusions

Dietary intervention (chow reversal) substantially improves metabolic, biochemical and histological hallmarks of NASH and fibrosis in GAN DIO-NASH mice. These benefits were reflected by progressive clearance of senescent hepatocellular cells, making the model suitable for profiling potential senotherapeutics in preclinical drug discovery for NASH.