bluuebunny/crossref_metadata_2025_split huggingface dataset:
M1-derived extracellular vesicles enhance photodynamic therapy and promote immunological memory in preclinical models of colon cancer
Authors: Huis in ‘t Veld Ruben V. , Lara Pablo , Jager Martine J. , Koning Roman I. , Ossendorp Ferry , Cruz Luis J. 
Published: June 2022

AbstractExtracellular vesicles (EVs) are promising drug carriers of photosensitizers for photodynamic therapy (PDT) in cancer treatment, due to their ability to circulate in blood and enter cells efficiently. The therapeutic potential of EVs has been suggested to depend on the type and physiological state of their cell of origin. However, the effects of deriving EVs from various cells in different physiological states on their antitumor capacity are rarely evaluated. In the present study, we compared the antitumor efficacy of EV-mediated PDT by incorporating the photosensitizer Zinc Phthalocyanine (ZnPc) into EVs from multiple cells sources. ZnPc was incorporated by a direct incubation strategy into EVs derived from immune cells (M1-like macrophages and M2-like macrophages), cancer cells (B16F10 melanoma cancer cells) and external sources (milk). Our data show that all EVs are suitable carriers for ZnPc and enable efficient PDT in vitro in co-culture models and in vivo. We observed that EV-mediated PDT initiates immunogenic cell death through the release and exposure of damage associated molecular patterns (DAMPs) on cancer cells, which subsequently induced dendritic cell (DC) maturation. Importantly, of all ZnPc-EVs tested, in absence of light only M1-ZnPc displayed toxicity to MC38, but not to DC, in monoculture and in co-culture, indicating specificity for cancer over immune cells. In MC38 tumor-bearing mice, only M1-ZnPc induced a tumor growth delay compared to control in absence of light. Interestingly, M1- but not M2-mediated PDT, induced complete responses against MC38 tumors in murine models (100% versus 38% of cases, respectively), with survival of all animals up to at least 60 days post inoculation. Finally, we show that all cured animals are protected from a rechallenge with MC38 cells, suggesting the induction of immunological memory after EV-mediated PDT. Together, our data show the importance of the cell type from which the EVs are obtained and highlight the impact of the immunological state of these cells on the antitumor efficacy of EV-mediated PDT.
Graphical Abstract
Interfacing DNA nanotechnology and biomimetic photonic complexes: advances and prospects in energy and biomedicine
Authors: Zhou Xu , Lin Su , Yan Hao 
Published: June 2022

AbstractSelf-assembled photonic systems with well-organized spatial arrangement and engineered optical properties can be used as efficient energy materials and as effective biomedical agents. The lessons learned from natural light-harvesting antennas have inspired the design and synthesis of a series of biomimetic photonic complexes, including those containing strongly coupled dye aggregates with dense molecular packing and unique spectroscopic features. These photoactive components provide excellent features that could be coupled to multiple applications including light-harvesting, energy transfer, biosensing, bioimaging, and cancer therapy. Meanwhile, nanoscale DNA assemblies have been employed as programmable and addressable templates to guide the formation of DNA-directed multi-pigment complexes, which can be used to enhance the complexity and precision of artificial photonic systems and show the potential for energy and biomedical applications. This review focuses on the interface of DNA nanotechnology and biomimetic photonic systems. We summarized the recent progress in the design, synthesis, and applications of bioinspired photonic systems, highlighted the advantages of the utilization of DNA nanostructures, and discussed the challenges and opportunities they provide.Graphical Abstract
Abplatin(IV) inhibited tumor growth on a patient derived cancer model of hepatocellular carcinoma and its comparative multi-omics study with cisplatin
Authors: Li Xing , Zhang Lingpu , Li Tuo , Li Shumu , Wu Wenjing , Zhao Lingyu , Xie Peng , Yang Jinqi , Li Peipei , Zhang Yangyang , Xiao Haihua , Yu Yingjie , Zhao Zhenwen 
Published: June 2022

Abstract
Background
Cisplatin, the alkylating agent of platinum(II) (Pt(II)), is the most common antitumor drug in clinic; however, it has many side effects, therefore it is higly desired to develop low toxicity platinum(IV) (Pt(IV)) drugs. Multi-omics analysis, as a powerful tool, has been frequently employed for the mechanism study of a certain therapy at the molecular level, which might be helpful for elucidating the mechanism of platinum drugs and facilitating their clinical application.

Methods
Strating form cisplatin, a hydrophobic Pt(IV) prodrug (CisPt(IV)) with two hydrophobic aliphatic chains was synthesized, and further encapsulated with a drug carrier, human serum albumin (HSA), to form nanoparticles, namely AbPlatin(IV). The anticancer effect of AbPlatin(IV) was investigated in vitro and in vivo. Moreover, transcriptomics, metabolomics and lipidomics were performed to explore the mechanism of AbPlatin(IV).

Results
Compared with cisplatin, Abplatin(IV) exhibited better tumor-targeting effect and greater tumor inhibition rate. Lipidomics study showed that Abplatin(IV) might induce the changes of BEL-7404 cell membrane, and cause the disorder of glycerophospholipids and sphingolipids. In addition, transcriptomics and metabolomics study showed that Abplatin(IV) significantly disturbed the purine metabolism pathway.

Conclusions
This research highlighted the development of Abplatin(IV) and the use of multi-omics for the mechanism elucidation of prodrug, which is the key to the clinical translation of prodrug.

Graphical Abstract
A clinical trial of super-stable homogeneous lipiodol-nanoICG formulation-guided precise fluorescent laparoscopic hepatocellular carcinoma resection
Authors: He Pan , Xiong Yongfu , Ye Jinfa , Chen Biaoqi , Cheng Hongwei , Liu Hao , Zheng Yating , Chu Chengchao , Mao Jingsong , Chen Aizheng , Zhang Yang , Li Jingdong , Tian Jie , Liu Gang 
Published: June 2022

AbstractBackgroundApplying traditional fluorescence navigation technologies in hepatocellular carcinoma is severely restricted by high false-positive rates, variable tumor differentiation, and unstable fluorescence performance.ResultsIn this study, a green, economical and safe nanomedicine formulation technology was developed to construct carrier-free indocyanine green nanoparticles (nanoICG) with a small uniform size and better fluorescent properties without any molecular structure changes compared to the ICG molecule. Subsequently, nanoICG dispersed into lipiodolviaa super-stable homogeneous intermixed formulation technology (SHIFT&nanoICG) for transhepatic arterial embolization combined with fluorescent laparoscopic hepatectomy to eliminate the existing shortcomings. A 52-year-old liver cancer patient was recruited for the clinical trial of SHIFT&nanoICG. We demonstrate that SHIFT&nanoICG could accurately identify and mark the lesion with excellent stability, embolism, optical imaging performance, and higher tumor-to-normal tissue ratio, especially in the detection of the microsatellite lesions (0.4 × 0.3 cm), which could not be detected by preoperative imaging, to realize a complete resection of hepatocellular carcinoma under fluorescence laparoscopy in a shorter period (within 2 h) and with less intraoperative blood loss (50 mL).ConclusionsThis simple and effective strategy integrates the diagnosis and treatment of hepatocellular carcinoma, and thus, it has great potential in various clinical applications.
Cyclosporine A loaded brain targeting nanoparticle to treat cerebral ischemia/reperfusion injury in mice
Authors: Liu Daozhou , Ji Qifeng , Cheng Ying , Liu Miao , Zhang Bangle , Mei Qibing , Huan Menglei , Zhou Siyuan 
Published: June 2022

AbstractBackgroundIschemic stroke is one of the main causes of death and disability in the world. The treatment for ischemic stroke is to restore blood perfusion as soon as possible. However, when ischemic brain tissue is re-perfused by blood, the mitochondrial permeability transition pore (mPTP) in neuron and microglia is excessively opened, resulting in the apoptosis of neuron and nerve inflammation. This aggravates nerve injury. Cyclosporine A (CsA) inhibits the over-opening of mPTP, subsequently reducing the release of ROS and the apoptosis of cerebral ischemia/reperfusion injured neuron and microglia. However, CsA is insoluble in water and present in high concentrations in lymphatic tissue. Herein, cerebral infarction tissue targeted nanoparticle (CsA@HFn) was developed to treat cerebral ischemia/reperfusion injury.ResultsCsA@HFn efficiently penetrated the blood-brain barrier (BBB) and selectively accumulated in ischemic area, inhibiting the opening of mPTP and ROS production in neuron. This subsequently reduced the apoptosis of neuron and the damage of BBB. Consequently, CsA@HFn significantly reduced the infarct area. Moreover, CsA@HFn inhibited the recruitment of astrocytes and microglia in ischemic region and polarized microglia into M2 type microglia, which subsequently alleviated the nerve inflammation.ConclusionsCsA@HFn showed a significant therapeutic effect on cerebral ischemia/reperfusion injury by alleviating the apoptosis of neuron, nerve inflammation and the damage of BBB in ischemic area. CsA@HFn has great potential in the treatment of ischemic stroke.Graphical Abstract
Development of a digital platform to improve community response to overdose and prevention among harm reduction organizations
Authors: Claborn Kasey , Creech Suzannah , Conway Fiona N. , Clinton Nina M. , Brinkley Katlyn T. , Lippard Elizabeth , Ramos Tristan , Samora Jake , Miri Aaron , Benzer Justin 
Published: June 2022

AbstractThe overdose crisis in the USA remains a growing and urgent public health concern. Over 108,000 people died due to overdose during 2021. Fatal and non-fatal overdoses are under-reported in the USA due to current surveillance methods. Systemic gaps in overdose data limit the opportunity for data-driven prevention efforts and resource allocation. This study aims to improve overdose surveillance and community response through developing a digital platform for overdose reporting and response among harm reduction organizations. We used a community-engaged, user-center design research approach. We conducted qualitative interviews with N = 44 overdose stakeholders including people who use drugs and harm reductionists. Results highlighted the need for a unified, multilingual reporting system uniquely tailored for harm reduction organizations. Anonymity, data transparency, protection from legal repercussions, data accuracy, and community-branded marketing emerged as key themes for the overdose platform. Emergent themes included the need for real-time data in a dashboard designed for community response and tailored to first responders and harm reduction organizations. This formative study provides the groundwork for improving overdose surveillance and data-driven response through the development of an innovative overdose digital platform.
Assessment of health state utilities in dermatology: an experimental time trade-off value set for the dermatology life quality index
Authors: Ruzsa Gábor , Rencz Fanni , Brodszky Valentin 
Published: June 2022

Abstract
Background
Dermatology Life Quality Index (DLQI) scores are used in many countries as access and reimbursement criteria for costly dermatological treatments. In this study we examined how time trade-off (TTO) utility valuations made by individuals from the general population are related to combinations of DLQI severity levels characterizing dermatologically relevant health states, with the ultimate purpose of developing a value set for the DLQI.

Methods
We used data from an online cross-sectional survey conducted in Hungary in 2020 (n = 842 after sample exclusions). Respondents were assigned to one of 18 random blocks and were asked to provide 10-year TTO valuations for the corresponding five hypothetical health states. To analyze the relationship between DLQI severity levels and utility valuations, we estimated linear, censored, ordinal, and beta regression models, complemented by two-part scalable models accommodating heterogeneity effects in respondents’ valuation scale usage. Successive severity levels (0–3) of each DLQI item were represented by dummy variables. We used cross-validation methods to reduce the initial set of 30 dummy variables and improve model robustness.

Results
Our final, censored linear regression model with 13 dummy variables had R2 = 0.136, thus accounting for 36.9% of the incremental explanatory power of a maximal (full-information) benchmark model (R2 = 0.148) over the uni-dimensional model (R2 = 0.129). Each DLQI item was found to have a negative effect on the valuation of health states, yet this effect was largely heterogeneous across DLQI items, and the relative contribution of distinctive severity levels also varied substantially. Overall, we found that the social/interpersonal consequences of skin conditions (in the areas of social and leisure activities, work and school, close personal relationships, and sexuality) had roughly twice as large disutility impact as the physical/practical aspects.

Conclusions
We have developed an experimental value set for the DLQI, which could prospectively be used for quantifying the quality-adjusted life years impact of dermatological treatments and serve as a basis for cost-effectiveness analyses. We suggest that, after validation of our main results through confirmatory studies, population-specific DLQI value sets could be developed and used for conducting cost-effectiveness analyses and developing financing guidelines in dermatological care.
EQ-5D-Y-3L and EQ-5D-Y-5L proxy report: psychometric performance and agreement with self-report
Authors: Fitriana Titi Sahidah , Purba Fredrick Dermawan , Stolk Elly , Busschbach Jan J. V. 
Published: June 2022

Abstract
Background
Self-report is the standard for measuring people’s health-related quality of life (HRQoL), including children. However, in certain circumstances children cannot report their own health. For this reason, children’s HRQoL measures often provide both a self-report and a proxy-report form. It is not clear whether the measurement properties will be the same for these two forms. We investigated whether it would be beneficial to extend the classification system of the EQ-5D-Y proxy questionnaire from 3 to 5 response levels. The agreement between self-report and proxy-report was assessed for both EQ-5D-Y measures.

Methods
The study included 286 pediatric patients and their caregivers as proxies. At three consecutive measurements—baseline, test–retest and follow-up—the proxies assessed the child’s HRQoL using the EQ-5D-Y-3L, EQ-5D-Y-5L, the PedsQL Generic, and matched disease-specific instruments. The proxy versions of EQ-5D-Y-3L and EQ-5D-Y-5L were compared in terms of feasibility, distribution properties, convergent validity, test–retest and responsiveness. Agreement between both EQ-5D-Y proxy versions to their respective self-report versions was assessed at baseline and follow-up.

Results
The proportion of missing responses was 1% for the EQ-5D-Y-3L and 1.4% for the EQ-5D-Y-5L. The frequency of health state with no problems in all dimensions (11111) was slightly lower for the EQ-5D-Y-5L (21.3% vs 16.7%). Regarding the convergent validity with the PedsQL and disease-specific measures, the proxy versions of EQ-5D-Y-3L and EQ-5D-Y-5L had similar magnitudes of associations between similar dimensions. The means of test–retest coefficients between the two versions of the EQ-5D-Y proxy were comparable (0.83 vs. 0.84). Regarding reported improved conditions, responsiveness of the EQ-5D-Y-5L proxy (26.6–54.1%) was higher than that of the EQ-5D-Y-3L proxy (20.7–46.4%). Except for acutely ill patients, agreement between the EQ-5D-Y-5L proxy and self-reports was at least moderate.

Conclusions
Extending the number of levels of the proxy version of EQ-5D-Y can improve the classification accuracy and the ability to detect health changes over time. The level structure of EQ-5D-Y-5L was associated with a closer agreement between proxy and self-report. The study findings support extending the EQ-5D-Y descriptive system from 3 to 5 levels when administered by a proxy, which is often the case in the pediatric population.
A pyroptosis-related gene signature predicts prognosis and immune microenvironment in hepatocellular carcinoma
Authors: Jin Yifeng , Pu Xiaofan , Ping Dongnan , Huang Chaojie , Ding Guoping , Cao Liping 
Published: June 2022

Abstract
Background
Hepatocellular carcinoma (HCC) is a highly malignant tumor with a very poor prognosis. Pyroptosis is an inflammatory form of cell death and plays an important role in cancer development. The prognostic value of pyroptosis-related genes (PRGs) in HCC has not been studied extensively.

Methods
Unsupervised consensus clustering analysis was performed to identify two subtypes based on the expression profiles of prognostic PRGs in the The Cancer Genome Atlas (TCGA) database, and the differences between the two subtypes were compared. A prognostic model based on four PRGs was established by further least absolute shrinkage and selection operator (LASSO) Cox regression analysis and multivariate Cox regression analysis.

Results
Two subtypes (clusters 1 and 2) were identified by consensus clustering based on prognostic PRGs in HCC. Survival outcomes, biological function, genomic alterations, immune cell infiltration, and immune checkpoint genes were compared between the subtypes. Cluster 2 had a worse survival outcome than cluster 1. Cluster 2 was enriched for hallmarks of cancer progression, TP53 mutation, tumor-promoting immune cells, and immune checkpoint genes, which may contribute to the poor prognosis. A prognostic risk signature that predicted the overall survival (OS) of patients was constructed and validated. Consequently, a risk score was calculated for each patient. Combined with the clinical characteristics, the risk score was found to be an independent prognostic factor for survival of HCC patients. Further analysis revealed that the risk score was closely associated with the levels of immune cell infiltration and the expression profiles of immune checkpoint genes.

Conclusions
Collectively, our study established a prognostic risk signature for HCC and revealed a significant correlation between pyroptosis and the HCC immune microenvironment.
Metastatic gastric adenocarcinoma to the uterine cervix—a case report and review of the literature
Authors: Bahall Vishal , De Barry Lance , Barrow Mickhaiel , Ramnarace Rene 
Published: June 2022

Abstract
Background
Poorly differentiated diffuse-type gastric adenocarcinoma often presents at an advanced stage. While gastric cancer typically metastasizes to the liver, lung and bone, metastasis to the uterine cervix is extremely rare. To our knowledge, less than forty cases have been described in the medical literature.

Case presentation
We report a case of a 47-year-old woman who presented to us with symptomatic uterine leiomyomas and subsequently underwent a successful total laparoscopic hysterectomy and bilateral salpingo-oophorectomy. The diagnosis of metastatic cancer involving the cervix was established incidentally on histopathology, which demonstrated atypical signet ring cells in the lymphovascular spaces of the cervix. Further investigations for a primary malignancy revealed a poorly differentiated diffuse-type gastric adenocarcinoma.

Conclusion
Gastric cancer involving the uterine cervix is rare and associated with a poor prognosis. When presented with isolated cervical metastases, the gastrointestinal tract should be considered as a possible primary source. Due to the limited publications on this clinical entity, we expect to raise awareness and study this unique manifestation of gastric cancer by presenting our case.
Exploring static and dynamic relationships between burden of disease and research funding in the United States
Authors: Nimgaonkar Alok , Mughal Anisa Y. , Heimer Hakon , Nimgaonkar Vishwajit , Greenstein Dede , Wright Alexandra 
Published: June 2022

Abstract
Background
The relationship between burden of disease and research funding has been examined cross-sectionally, but temporal patterns have not been investigated. It is logical to assume that temporal improvements in disability-adjusted life-years (DALYs) reflect benefits from research funding; such assumptions are tempered by an unknown lag time for emergence of benefits from research.

Methods
We studied National Institutes of Health (NIH) research fund allocations and United States DALY estimates for overlapping disease categories (matched disease categories, MDC, N = 38). Using a general linear model, we separately analysed DALYs for MDCs in 2017 in relation to NIH research allocations in 2017 and 2007. We also examined how changes in DALYs were related to cumulative NIH research funding (2006–2017). After regressing DALY change on summed funding, we obtained model residuals as estimates of the discrepancy for each MDC between observed and expected change in burden, given funding.

Results
In 2017, there was a positive association between NIH research fund allocations and DALYs for the same year (F1,36 = 16.087, p = 0.0002921; slope = 0.35020; model R2 = 0.3088), suggesting proportionate allocation. There was a positive association between 2017 DALYs and 2007 NIH research allocation, implying a beneficial impact of research (F1,36 = 15.754, p = 0.0003; slope = 0.8845; model R2 = 0.3044). In contrast, there was a nonsignificant association between summed NIH funding and percent change in DALYs over 2006–2017 (F1,36 = 0.199; p = 0.65; beta coefficient = −1.144). When MDCs were ordered based on residuals, HIV/AIDS ranked first. Mental, neurologic or substance abuse (MNS) disorders comprised most residuals in the lower half.

Conclusions
NIH fund allocation is proportional to DALYs for MDCs. Temporal changes in DALYs vary by MDCs, but they are not significantly related to cumulative research outlays. Further analysis of temporal changes in DALYs could help to inform research outlays for MDCs and to study the impact of research.