bluuebunny/crossref_metadata_2025_split huggingface dataset:
Gut mycobiome as a potential non-invasive tool in early detection of lung adenocarcinoma: a cross-sectional study
Authors: Liu Qingyan , Zhang Weidong , Pei Yanbin , Tao Haitao , Ma Junxun , Li Rong , Zhang Fan , Wang Lijie , Shen Leilei , Liu Yang , Jia Xiaodong , Hu Yi 
Published: October 2023

Abstract
Background
The gut mycobiome of patients with lung adenocarcinoma (LUAD) remains unexplored. This study aimed to characterize the gut mycobiome in patients with LUAD and evaluate the potential of gut fungi as non-invasive biomarkers for early diagnosis.

Methods
In total, 299 fecal samples from Beijing, Suzhou, and Hainan were collected prospectively. Using internal transcribed spacer 2 sequencing, we profiled the gut mycobiome. Five supervised machine learning algorithms were trained on fungal signatures to build an optimized prediction model for LUAD in a discovery cohort comprising 105 patients with LUAD and 61 healthy controls (HCs) from Beijing. Validation cohorts from Beijing, Suzhou, and Hainan comprising 44, 17, and 15 patients with LUAD and 26, 19, and 12 HCs, respectively, were used to evaluate efficacy.

Results
Fungal biodiversity and richness increased in patients with LUAD. At the phylum level, the abundance of Ascomycota decreased, while that of Basidiomycota increased in patients with LUAD. Candida and Saccharomyces were the dominant genera, with a reduction in Candida and an increase in Saccharomyces, Aspergillus, and Apiotrichum in patients with LUAD. Nineteen operational taxonomic unit markers were selected, and excellent performance in predicting LUAD was achieved (area under the curve (AUC) = 0.9350) using a random forest model with outcomes superior to those of four other algorithms. The AUCs of the Beijing, Suzhou, and Hainan validation cohorts were 0.9538, 0.9628, and 0.8833, respectively.

Conclusions
For the first time, the gut fungal profiles of patients with LUAD were shown to represent potential non-invasive biomarkers for early-stage diagnosis.
Hypoxia enhances anti-fibrotic properties of extracellular vesicles derived from hiPSCs via the miR302b-3p/TGFβ/SMAD2 axis
Authors: Paw Milena , Kusiak Agnieszka A. , Nit Kinga , Litewka Jacek J. , Piejko Marcin , Wnuk Dawid , Sarna Michał , Fic Kinga , Stopa Kinga B. , Hammad Ruba , Barczyk-Woznicka Olga , Cathomen Toni , Zuba-Surma Ewa , Madeja Zbigniew , Ferdek Paweł E. , Bobis-Wozowicz Sylwia 
Published: October 2023

Abstract
Background
Cardiac fibrosis is one of the top killers among fibrotic diseases and continues to be a global unaddressed health problem. The lack of effective treatment combined with the considerable socioeconomic burden highlights the urgent need for innovative therapeutic options. Here, we evaluated the anti-fibrotic properties of extracellular vesicles (EVs) derived from human induced pluripotent stem cells (hiPSCs) that were cultured under various oxygen concentrations.

Methods
EVs were isolated from three hiPSC lines cultured under normoxia (21% O2; EV-N) or reduced oxygen concentration (hypoxia): 3% O2 (EV-H3) or 5% O2 (EV-H5). The anti-fibrotic activity of EVs was tested in an in vitro model of cardiac fibrosis, followed by a detailed investigation of the underlying molecular mechanisms. Sequencing of EV miRNAs combined with bioinformatics analysis was conducted and a selected miRNA was validated using a miRNA mimic and inhibitor. Finally, EVs were tested in a mouse model of angiotensin II-induced cardiac fibrosis.

Results
We provide evidence that an oxygen concentration of 5% enhances the anti-fibrotic effects of hiPS-EVs. These EVs were more effective in reducing pro-fibrotic markers in activated human cardiac fibroblasts, when compared to EV-N or EV-H3. We show that EV-H5 act through the canonical TGFβ/SMAD pathway, primarily via miR-302b-3p, which is the most abundant miRNA in EV-H5. Our results show that EV-H5 not only target transcripts of several profibrotic genes, including SMAD2 and TGFBR2, but also reduce the stiffness of activated fibroblasts. In a mouse model of heart fibrosis, EV-H5 outperformed EV-N in suppressing the inflammatory response in the host and by attenuating collagen deposition and reducing pro-fibrotic markers in cardiac tissue.

Conclusions
In this work, we provide evidence of superior anti-fibrotic properties of EV-H5 over EV-N or EV-H3. Our study uncovers that fine regulation of oxygen concentration in the cellular environment may enhance the anti-fibrotic effects of hiPS-EVs, which has great potential to be applied for heart regeneration.

Graphical Abstract
Joint association of sedentary behavior and vitamin D status with mortality among cancer survivors
Authors: Yu Yu , Cheng Sijing , Huang Hao , Deng Yu , Cai Chi , Gu Min , Chen Xuhua , Niu Hongxia , Hua Wei 
Published: October 2023

Abstract
Background
Sedentary behavior and vitamin D deficiency are independent risk factors for mortality in cancer survivors, but their joint association with mortality has not been investigated.

Methods
We analyzed data from 2914 cancer survivors who participated in the National Health and Nutrition Examination Survey (2007–2018) and followed up with them until December 31, 2019. Sedentary behavior was assessed by self-reported daily hours of sitting, and vitamin D status was measured by serum total 25-hydroxyvitamin D (25(OH)D) levels.

Results
Among 2914 cancer survivors, vitamin D deficiency was more prevalent in those with prolonged daily sitting time. During up to 13.2 years (median, 5.6 years) of follow-up, there were 676 deaths (cancer, 226; cardiovascular disease, 142; other causes, 308). The prolonged sitting time was associated with a higher risk of all-cause and noncancer mortality, and vitamin D deficiency was associated with a higher risk of all-cause and cancer mortality. Furthermore, cancer survivors with both prolonged sitting time (≥ 6 h/day) and vitamin D deficiency had a significantly higher risk of all-cause (HR, 2.05; 95% CI: 1.54–2.72), cancer (HR, 2.33; 95% CI, 1.47–3.70), and noncancer mortality (HR, 1.91; 95% CI, 1.33–2.74) than those with neither risk factor after adjustment for potential confounders.

Conclusions
In a nationally representative sample of U.S. cancer survivors, the joint presence of sedentary behavior and vitamin D deficiency was significantly associated with an increased risk of all-cause and cancer-specific mortality.
Do alternative tobacco products induce less adverse respiratory risk than cigarettes?
Authors: Bhat Tariq A. , Kalathil Suresh G. , Leigh Noel , Hutson Alan , Goniewicz Maciej L. , Thanavala Yasmin M. 
Published: October 2023

Abstract
Rationale
Due to the relatively short existence of alternative tobacco products, gaps exist in our current understanding of their long-term respiratory health effects. We therefore undertook the first-ever side-by-side comparison of the impact of chronic inhalation of aerosols emitted from electronic cigarettes (EC) and heated tobacco products (HTP), and combustible cigarettes (CC) smoke.

Objectives
To evaluate the potential differential effects of alternative tobacco products on lung inflammatory responses and efficacy of vaccination in comparison to CC.

Methods
Mice were exposed to emissions from EC, HTP, CC, or air for 8 weeks. BAL and lung tissue were analyzed for markers of inflammation, lung damage, and oxidative stress. Another group was exposed for 12 weeks and vaccinated and challenged with a bacterial respiratory infection. Antibody titers in BAL and sera and pulmonary bacterial clearance were assessed.

Main results
EC- and HTP-aerosols significantly augmented lung immune cell infiltrates equivalent to that achieved following CC-exposure. HTP and CC significantly increased neutrophil numbers compared to EC. All products augmented numbers of B cells, T cells, and pro-inflammatory IL17A+ T cells in the lungs. Decreased lung antioxidant activity and lung epithelial and endothelial damage was induced by all products. EC and HTP differentially augmented inflammatory cytokines/chemokines in the BAL. Generation of immunity following vaccination was impaired by EC and HTP but to a lesser extent than CC, with a CC > HTP > EC hierarchy of suppression of pulmonary bacterial clearance.

Conclusions
HTP and EC-aerosols induced a proinflammatory pulmonary microenvironment, lung damage, and suppressed efficacy of vaccination.
Awareness and acceptability of malaria vaccine among caregivers of under-5 children in Northern Nigeria
Authors: Ajayi Mary Yetunde , Emeto Daniel Chukwuyere 
Published: October 2023

Abstract
Background
Malaria vaccine, RTS, S/AS01, has demonstrated modest efficacy against malaria and holds promises for children living in areas where malaria transmission is high. This study assessed caregivers’ awareness and willingness to accept the vaccine and provided vital information for policymakers, health workers, and social mobilizers on critical areas to focus on promoting the new vaccine uptake before its arrival for use in Nigeria.

Methods
The study was a community-based cross-sectional survey. A multistage sampling technique was used to select four states in Northern Nigeria, where the incidence and prevalence of malaria are highest in the country and 504 caregivers of under-five children were interviewed. A semi-structured interviewer-administered questionnaire was used and data analysis was done with p-value at 0.05.

Results
Two hundred and three (40.3%) respondents were aware of malaria vaccine while four hundred and sixty-three (91.9%) were willing to accept the vaccine when it is introduced for use in the country. Level of education (AOR; 0.42; CI 0.23–0.78), employment status (AOR; 3.03; CI 1.82–5.03), previous experience of other childhood vaccinations (AOR; 4.87; CI 2.89–8.20), and caregivers having suffered malaria within the last one year (AOR; 1.85; CI 1.10 −3.13) significantly predicted malaria vaccine awareness. Awareness of the new malaria vaccine (AOR = 6.88; 95% CI 1.53–30.99), and previous experience of other childhood vaccinations (AOR = 6.16; 95% CI 2.54–14.94) were significant predictors of the vaccine acceptability.

Conclusion
Caregiver’s awareness of the new malaria vaccine was inadequate. There is a need to intensify efforts on social and behavioural communication change activities tailoring messages on the vaccine to address uptake hesitancy. Also, an intense community engagement with focus on providing information on the safety of the vaccine is encouraged.
Dietary pesticide exposure and non-communicable diseases and mortality: a systematic review of prospective studies among adults
Authors: Baudry Julia , Rebouillat Pauline , Samieri Cécilia , Berlivet Justine , Kesse-Guyot Emmanuelle 
Published: October 2023

Abstract
Background
Research on the effect of pesticide exposure on health has been largely focused on occupational settings. Few reviews have synthesized the associations between dietary pesticide exposure and health outcomes in non-occupationally exposed adults.

Objective
We aim to summarize the evidence regarding dietary pesticide exposure and non-communicable diseases (NCD) in adults, using a systematic review of prospective studies.

Methods
Electronic and manual searches were performed until July 2023. The inclusion criteria were the following: 1) adults aged ≥ 18years, 2) (non)-randomized trials, prospective cohort studies, 3) dietary exposure to pesticides. A bias analysis was carried out using the Nutrition Evidence Systematic Review guidelines based on the Cochrane ROBINS-I.

Results
A total of 52 studies were retrieved and 6 studies that met the above criteria were included. Studies were conducted either in France or in the United States. The studies investigated the risk of cancer (n = 3), diabetes (n = 1), cardiovascular diseases (n = 1), and mortality (n = 1). The quality of the studies varied with overall grades derived from the bias analysis ranging from low to moderate bias. The level of evidence was estimated as low for the risk of cancer while the grading was not assignable for other outcomes, as only one study per outcome was available.

Conclusions
Although further research is warranted to examine more in depth the relationships between low-dose chronic exposure to pesticides through diet and NCD outcomes in non-occupationally-exposed adults, studies suggest a possible role of exposure to dietary pesticide on health. Standardized methodological guidelines should also be proposed to allow for comparison across studies.
Targeting and repolarizing M2-like tumor-associated macrophage-mediated MR imaging and tumor immunotherapy by biomimetic nanoparticles
Authors: Chong Lijuan , Jiang Yao-Wen , Wang Dongxu , Chang Pengzhao , Xu Kai , Li Jingjing 
Published: October 2023

AbstractAnti-tumor M1-like and pro-tumor M2-like tumor-associated macrophages (TAMs) coexist in tumor microenvironments (TME). The adverse effects of these M1/M2 subsets on tumors directly affect the current strategies to improve anti-tumor immune response. Therefore, it has attracted great attention to change the tumor immunosuppressive microenvironment by reprogramming TAMs. In this paper, we constructed biomimetic nanoparticles (HMMDN-Met@PM) targeting M2-like TAMs for macrophage re-polarization. In detail, the core of the biomimetic nanoparticles is metformin-loaded hollow mesoporous manganese dioxide nanoparticles (HMMDN-Met). Benefited from the hollow and porous structure of HMMDN, metformin, the regulator of M1/M2 adopted in this work, can be easily and widely loaded into HMMDN. Moreover, macrophage membranes were utilized for HMMDN-Met coating (HMMDN-Met@MM) to prevent the premature drug leakage and provide specific molecular recognition/TME targeting. In addition, M2 macrophage targeting peptide (M2pep) was modified on the surface of macrophage membrane to specifically deliver the drug to M2-like TAMs to promote the polarization of M2 to M1 macrophages. Through in vitro and in vivo studies, we found that the expression of surface markers and inflammatory factors CD206, Arg-1 and IL-10 of type M2 macrophages decreased, while the surface markers of type M1 macrophages and the expression of inflammatory factors CD80, TNF-α and iNOS increased, indicating the successful re-polarization of M2 macrophages and finally realizing the inhibition of tumor growth. At the same time, under the acidic and GSH conditions of tumor, HMMDN was decomposed into Mn2+, which is a contrast agent for magnetic resonance imaging, thus realizing the tracking of tumor. This work practices biomimetic nanosystem in targeted imaging and immunotherapy, paving the way for strategy designing for tumor inhibition.
KRASG12C inhibition using MRTX1257: a novel radio-sensitizing partner
Authors: Laurent Pierre-Antoine , Milic Marina , Quevrin Clément , Meziani Lydia , Liu Winchygn , Morel Daphné , Signolle Nicolas , Clémenson Céline , Levy Antonin , Mondini Michele , Deutsch Eric 
Published: October 2023

Abstract
Background
KRAS activating mutations are considered the most frequent oncogenic drivers and are correlated with radio-resistance in multiple cancers including non-small cell lung cancer (NSCLC) and colorectal cancer. Although KRAS was considered undruggable until recently, several KRAS inhibitors have recently reached clinical development. Among them, MRTX849 (Mirati Therapeutics) showed encouraging clinical outcomes for the treatment of selected patients with KRASG12C mutated NSCLC and colorectal cancers. In this work, we explore the ability of MRTX1257, a KRASG12C inhibitor analogous to MRTX849, to radio-sensitize KRASG12C+/+ mutated cell lines and tumors.

Methods
Both in vitro and in vivo models of radiotherapy (RT) in association with MRTX1257 were used, with different RAS mutational profiles. We assessed in vitro the radio-sensitizing effect of MRTX1257 in CT26 KRASG12C+/+, CT26 WT, LL2 WT and LL2 NRAS KO (LL2 NRAS−/−) cell lines. In vivo, we used syngeneic models of subcutaneous CT26 KRASG12C+/+ tumors in BALB/c mice and T cell deficient athymic nu/nu mice to assess both the radio-sensitizing effect of MRTX1257 and its immunological features.

Results
MRTX1257 was able to radio-sensitize CT26 KRASG12C+/+ cells in vitro in a time and dose dependent manner. Moreover, RT in association with MRTX1257 in BALB/c mice bearing CT26 KRASG12C+/+ subcutaneous tumors resulted in an observable cure rate of 20%. However, no durable response was observed with similar treatment in athymic nude mice. The analysis of the immune microenvironment of CT26 KRASG12C+/+ tumors following RT and MRTX1257 showed an increase in the proportion of various cell subtypes including conventional CD4 + T cells, dendritic cells type 2 (cDC2) and inflammatory monocytes. Furthermore, the expression of PD-L1 was dramatically down-regulated within both tumor and myeloid cells, thus illustrating the polarization of the tumor microenvironment towards a pro-inflammatory and anti-tumor phenotype following the combined treatment.

Conclusion
This work is the first to demonstrate in vitro as in vivo the radio-sensitizing effect of MRTX1257, a potent KRASG12C inhibitor compatible with oral administration, in CT26 KRASG12C mutated cell lines and tumors. This is a first step towards the use of new combinatorial strategies using KRAS inhibitors and RT in KRASG12C mutated tumors, which are the most represented in NSCLC with 14% of patients harboring this mutational profile.
National governance and excess mortality due to COVID-19 in 213 countries: a retrospective analysis and perspectives on future pandemics
Authors: da Silva Ricardo Eccard , Novaes Maria Rita Carvalho Garbi , de Oliveira Cesar , Guilhem Dirce Bellezi 
Published: October 2023

Abstract
Background
National governance may have influenced the response of institutions to the Covid-19 pandemic, being a key factor in preparing for the next pandemics. The objective was to analyze the association between excess mortality due to COVID-19 (daily and cumulative per 100 thousand people) and national governance indicators in 213 countries.

Method
Multiple linear regression models using secondary data from large international datasets that are in the public domain were performed. Governance indicators corresponded to six dimensions: (i) Voice and Accountability; (ii) Political Stability and Absence of Violence/Terrorism; (iii) Government Effectiveness; (iv) Regulatory Quality; (v) Rule of Law and (vi) Control of Corruption. The statistical analysis consisted of adjusting a multiple linear regression model. Excess mortality due to COVID-19 was adjusted for potential confounding factors (demographic, environmental, health, economic, and ethnic variables).

Results
The indicators Control of Corruption, Government Effectiveness, Regulatory Quality and Rule of Law had a significant inverse association (p < 0.0001) with the estimated excess mortality in 2020, 2021 and 2022. Furthermore, the governance indicators had a direct significant association (p < 0.0001) with the vaccination variables (People_fully_vaccinated; Delivered population; The total number of vaccination doses administered per 100 people at the country level), except for the variables Vaccination policies and Administration of first dose, which were inversely associated. In countries with better governance, COVID-19 vaccination was initiated earlier.

Conclusion
Better national governance indicators were associated with lower excess mortality due to COVID-19 and faster administration of the first dose of the COVID-19 vaccine.
Palliative radiotherapy for tumor bleeding in patients with unresectable pancreatic cancer: a single-center retrospective study
Authors: Shibuki Taro , Sasaki Mitsuhito , Yamaguchi Shota , Inoue Kanae , Taira Tomonao , Satake Tomoyuki , Watanabe Kazuo , Imaoka Hiroshi , Mitsunaga Shuichi , Fujisawa Takeshi , Tomizawa Kento , Oyoshi Hidekazu , Nakamura Masaki , Hojo Hidehiro , Ikeda Masafumi 
Published: October 2023

Abstract
Background
Patients with unresectable pancreatic cancer (PC) sometimes experience gastrointestinal bleeding (GIB) due to tumor invasion of the gastrointestinal tract (tumor bleeding); no standard treatment has been established yet for this complication. Palliative radiotherapy (PRT) could be promising, however, there are few reports of PRT for tumor bleeding in patients with unresectable PC. Therefore, we evaluated the outcomes of PRT for tumor bleeding in patients with unresectable PC.

Methods
We reviewed the medical records of patients with unresectable PC diagnosed at our institution between May 2013 and January 2022, and identified patients with endoscopically confirmed tumor bleeding who had received PRT. PRT was administered at a total dose of 30 Grays (Gy) in 10 fractions, 20 Gy in 5 fractions, or 8 Gy in a single fraction, and the dose selection was left to the discretion of the attending radiation oncologists.

Results
During the study period, 2562 patients were diagnosed as having unresectable PC at our hospital, of which 225 (8.8%) developed GIB. Among the 225 patients, 63 (2.5%) were diagnosed as having tumor bleeding and 20 (0.8%) received PRT. Hemostasis was achieved in 14 of the 20 patients (70%) who received PRT, and none of these patients developed grade 3 or more adverse events related to the PRT. The median time to hemostasis was 8.5 days (range 7–14 days). The rebleeding rate was 21.4% (3/14). The median hemoglobin level increased significantly (p < 0.001) from 5.9 to 9.1 g/dL, and the median volume of red blood cell transfusion tended (p = 0.052) to decrease, from 1120 mL (range 280–3360 mL) to 280 mL (range 0–5560 mL) following the PRT. The median overall survival (OS) was 52 days (95% confidence interval [CI] 39–317). Of the 14 patients in whom hemostasis was achieved following PRT, chemotherapy could be started/resumed in seven patients (50%), and the median OS in these patients was 260 days (95% CI 76–not evaluable [NE]). Three patients experienced rebleeding (21.4%), on days 16, 22, and 25, after the start of PRT.

Conclusion
This study showed that PRT is an effective and safe treatment modality for tumor bleeding in patients with unresectable PC.
Novel screw-cable integrated system(SCIS) for minimally invasive treatment of patella transverse fractures: a finite element analysis
Authors: Liu Songyang , Liu Shen , Gu Feng , Wei Xing , Liang Yonghui 
Published: October 2023

Abstract
Background
The most recommended method for treating transverse patella fractures is modified tension band wiring (MTBW). However, the optimal instrument for use with MTBW is still undetermined. Hence, we aimed to design a novel screw-cable integrated system (SCIS) and compare its biomechanical characteristics with Kirschner-wire, SCIS, and Cable-Pin systems in treating transverse patellar fracture.

Methods
A finite-element (FE) model of transverse patella fracture was created. The fracture model was fixed with either K-wire, SCIS, or Cable-pin. Different tension force loading (400 N and 800 N), direction(0° and 45°), and screw or K-wire depth(5 mm and 10 mm) were set. The maximum displacement of the fragment and maximum gap opening were measured by using FE analysis.

Results
Compared with the K-wire and Cable-pin system, SCIS increased the stability of the fractured patella by reducing fragment displacement and gap opening. Under 400 N loading in the direction 45°, SCIS with screw placing at 5-mm depth reduced the maximum fragment displacement (0.43 mm) by 49.62% and 26%, respectively, compared with the K-wire (0.22 mm) and Cable-pin (0. 22 mm) group. Meanwhile, the gap opening in SCIS (0.05 mm) was reduced by 83% and 59.8% (0.05 to 0.18) compared with the K-wire (0.30 mm) and Cable-pin (0.18 mm) group.

Conclusion
SCIS demonstrated improved biomechanical stability for treating transverse patellar fractures compared to MTBW with Kirschner wire and the Cable-Pin system. Finite element analysis showed SCIS substantially reduced fracture fragment displacement and gap opening under various loading conditions.