bluuebunny/crossref_metadata_2025_split huggingface dataset:
Multi-omic signatures of sarcoidosis and progression in bronchoalveolar lavage cells
Authors: Konigsberg Iain R. , Lin Nancy W. , Liao Shu-Yi , Liu Cuining , MacPhail Kristyn , Mroz Margaret M. , Davidson Elizabeth , Restrepo Clara I. , Sharma Sunita , Li Li , Maier Lisa A. , Yang Ivana V. 
Published: July 2024

Abstract
Background
Sarcoidosis is a heterogeneous granulomatous disease with no accurate biomarkers of disease progression. Therefore, we profiled and integrated the DNA methylome, mRNAs, and microRNAs to identify molecular changes associated with sarcoidosis and disease progression that might illuminate underlying mechanisms of disease and potential biomarkers.

Methods
Bronchoalveolar lavage cells from 64 sarcoidosis subjects and 16 healthy controls were used. DNA methylation was profiled on Illumina HumanMethylationEPIC arrays, mRNA by RNA-sequencing, and miRNAs by small RNA-sequencing. Linear models were fit to test for effect of sarcoidosis diagnosis and progression phenotype, adjusting for age, sex, smoking, and principal components of the data. We built a supervised multi-omics model using a subset of features from each dataset.

Results
We identified 1,459 CpGs, 64 mRNAs, and five miRNAs associated with sarcoidosis versus controls and four mRNAs associated with disease progression. Our integrated model emphasized the prominence of the PI3K/AKT1 pathway, which is important in T cell and mTOR function. Novel immune related genes and miRNAs including LYST, RGS14, SLFN12L, and hsa-miR-199b-5p, distinguished sarcoidosis from controls. Our integrated model also demonstrated differential expression/methylation of IL20RB, ABCC11, SFSWAP, AGBL4, miR-146a-3p, and miR-378b between non-progressive and progressive sarcoidosis.

Conclusions
Leveraging the DNA methylome, transcriptome, and miRNA-sequencing in sarcoidosis BAL cells, we detected widespread molecular changes associated with disease, many which are involved in immune response. These molecules may serve as diagnostic/prognostic biomarkers and/or drug targets, although future testing is required for confirmation.
Assessing receptivity to malaria using case surveillance and forest data in a near-elimination setting in northeast Thailand
Authors: Walshe Rebecca , Pongsoipetch Kulchada , Mukem Suwanna , Kamsri Tanong , Singkham Navarat , Sudathip Prayuth , Kitchakarn Suravadee , Maude Rapeephan Rattanawongnara , Maude Richard James 
Published: July 2024

Abstract
Background
Thailand aimed to eliminate malaria by 2024, and as such is planning for future prevention of re-establishment in malaria free provinces. Understanding the receptivity of local areas to malaria allows the appropriate targeting of interventions. Current approaches to assessing receptivity involve collecting entomological data. Forest coverage is known to be associated with malaria risk, as an environment conducive to both vector breeding and high-risk human behaviours.

Methods
Geolocated, anonymized, individual-level surveillance data from 2011 to 2021 from the Thai Division of Vector-Borne Disease (DVBD) was used to calculate incidence and estimated Rc at village level. Forest cover was calculated using raster maps of tree crown cover density and year of forest loss from the publicly available Hansen dataset. Incidence and forest cover were compared graphically and using Spearman’s rho. The current foci classification system was applied to data from the last 5 years (2017–2021) and forest cover for 2021 compared between the classifications. A simple risk score was developed to identify villages with high receptivity.

Results
There was a non-linear decrease in annual cases by 96.6% (1061 to 36) across the two provinces from 2011 to 2021. Indigenous Annual Parasite Index (API) and approximated Rc were higher in villages in highly forested subdistricts, and with higher forest cover within 5 km. Forest cover was also higher in malaria foci which consistently reported malaria cases each year than those which did not. An Rc > 1 was only reported in villages in subdistricts with > 25% forest cover. When applying a simple risk score using forest cover and recent case history, the classifications were comparable to those of the risk stratification system currently used by the DVBD.

Conclusions
There was a positive association between forest coverage around a village and indigenous malaria cases. Most local transmission was observed in the heavily forested subdistricts on the international borders with Laos and Cambodia, which are where the most receptive villages are located. These areas are at greater risk of importation of malaria due to population mobility and forest-going activities. Combining forest cover and recent case surveillance data with measures of vulnerability may be useful for prediction of malaria recurrence risk.
Infection microenvironment-triggered nanoparticles eradicate MRSA by thermally amplified chemodynamic therapy and M1 macrophage
Authors: Hong Qimin , Zhang Wei , Liu Zhen , Li Bo , Liu Xi , Wang Zhinan , Wang Rui , Yang Jianping , Nie Bin’en , Yue Bing 
Published: July 2024

AbstractIt is of great significance to develop a novel approach to treat bacterial infections, as the frequent misuse of antibiotics leads to the serious problem of bacterial resistance. This study proposed antibiotic-free antibacterial nanoparticles for eliminating methicillin-resistant Staphylococcus aureus (MRSA) based on a multi-model synergistic antibacterial ability of chemodynamic therapy (CDT), photothermal effect, and innate immunomodulation. Specifically, a polydopamine (PDA) layer coated and Ag nanoparticles loaded core-shell structure Fe3O4 nanoparticles (Fe3O4@PDA-Ag) is prepared. The Fe3O4 catalyzes H2O2 present in acidic microenvironment of bacterial infection into more toxic reactive oxygen species (ROS) and synergizes with the released Ag ions to exert a stronger bactericidal capacity, which can be augmented by photothermal action of PDA triggered by near-infrared light and loosen the biofilm by photothermal action to promote the penetration of ROS and Ag ion into the biofilm, result in disrupting biofilm structure along with killing encapsulated bacteria. Furthermore, Fe3O4@PDA-Ag exerts indirect antibacterial effects by promoting M1 macrophage polarizing. Animal models demonstrated that Fe3O4@PDA-Ag effectively controlled MRSA-induced infections through photothermal enhanced CDT, Ag+ releasing, and macrophage-mediated bactericidal properties. The acid-triggered antibacterial nanoparticles are expected to combat drug-resistant bacteria infection.
Graphical abstract
Magnetothermal-activated gene editing strategy for enhanced tumor cell apoptosis
Authors: Li Mingyuan , Li Siqian , Guo YueDong , Hu Ping , Shi Jianlin 
Published: July 2024

AbstractPrecise and effective initiation of the apoptotic mechanism in tumor cells is one of the most promising approaches for the treatment of solid tumors. However, current techniques such as high-temperature ablation or gene editing suffer from the risk of damage to adjacent normal tissues. This study proposes a magnetothermal-induced CRISPR-Cas9 gene editing system for the targeted knockout of HSP70 and BCL2 genes, thereby enhancing tumor cell apoptosis. The magnetothermal nanoparticulate platform is composed of superparamagnetic ZnCoFe2O4@ZnMnFe2O4 nanoparticles and the modified polyethyleneimine (PEI) and hyaluronic acid (HA) on the surface, on which plasmid DNA can be effectively loaded. Under the induction of a controllable alternating magnetic field, the mild magnetothermal effect (42℃) not only triggers dual-genome editing to disrupt the apoptosis resistance mechanism of tumor cells but also sensitizes tumor cells to apoptosis through the heat effect itself, achieving a synergistic therapeutic effect. This strategy can precisely regulate the activation of the CRISPR-Cas9 system for tumor cell apoptosis without inducing significant damage to healthy tissues, thus providing a new avenue for cancer treatment.
Comparing patient- and proxy-reported health-related quality of life of frail older patients at the emergency department
Authors: Ha Joey Wei Yee , Pereira Michelle Jessica , Chong Edward Kah Chun , Molina Joseph Antonio De Castro , Lim Wee Shiong 
Published: July 2024

Abstract
Purpose
To examine agreement between patient- and proxy-reported Health-Related Quality of Life (HRQoL) scores, and their associations with clinical measures and patient demographics.

Methods
We examined the patient-proxy agreement in HRQoL within a cohort of community-dwelling frail older patients (Clinical Frailty Scale [CFS] score 4–6) planned for discharge from the Emergency Department (ED) of a 1700-bed tertiary hospital in Singapore. Patients were recruited as part of the Emergency Department Interventions for Frailty (EDIFY) program, a quasi-experimental study evaluating the effectiveness of a multicomponent frailty intervention (MFI) in maintaining or improving functional outcomes. HRQoL was measured using the EuroQoL five-dimensional questionnaire (EQ-5D-5L) for patients and proxies. We analysed a sample of dyadic-reported HRQoL to explore the inter-rater agreement using intraclass correlation coefficients (ICC), and the influencing factors of concordance.

Results
We recruited 140 participants with 23 pairs of patient-proxy dyads having concurrent EQ-5D reported. There was poor inter-rater agreement between patient- and proxy-reported EQ-5D (ICC 0.18) with proxies perceiving poorer average HRQoL than patients. On the domain level, there was poor agreement in self-care and pain domains (ICC − 0.07 and 0.20), where proxies perceived more problems than patients. In multivariate regressions, lower frailty scores were associated with poorer agreement in EQ-5D scores (p < 0.05).

Conclusion
In conclusion, our findings demonstrate differences between patient- and proxy-reported HRQoL outcomes among frail older patients, with significant discordance observed among patients who are “less frail”. Hence, proxy-reported responses should be interpreted with care especially when the abovementioned characteristics are present in an older patient.
Comparison of data fusion strategies for automated prostate lesion detection using mpMRI correlated with whole mount histology
Authors: Gunashekar Deepa Darshini , Bielak Lars , Oerther Benedict , Benndorf Matthias , Nedelcu Andrea , Hickey Samantha , Zamboglou Constantinos , Grosu Anca-Ligia , Bock Michael 
Published: July 2024

Abstract
Background
In this work, we compare input level, feature level and decision level data fusion techniques for automatic detection of clinically significant prostate lesions (csPCa).

Methods
Multiple deep learning CNN architectures were developed using the Unet as the baseline. The CNNs use both multiparametric MRI images (T2W, ADC, and High b-value) and quantitative clinical data (prostate specific antigen (PSA), PSA density (PSAD), prostate gland volume & gross tumor volume (GTV)), and only mp-MRI images (n = 118), as input. In addition, co-registered ground truth data from whole mount histopathology images (n = 22) were used as a test set for evaluation.

Results
The CNNs achieved for early/intermediate / late level fusion a precision of 0.41/0.51/0.61, recall value of 0.18/0.22/0.25, an average precision of 0.13 / 0.19 / 0.27, and F scores of 0.55/0.67/ 0.76. Dice Sorensen Coefficient (DSC) was used to evaluate the influence of combining mpMRI with parametric clinical data for the detection of csPCa. We compared the DSC between the predictions of CNN’s trained with mpMRI and parametric clinical and the CNN’s trained with only mpMRI images as input with the ground truth. We obtained a DSC of data 0.30/0.34/0.36 and 0.26/0.33/0.34 respectively. Additionally, we evaluated the influence of each mpMRI input channel for the task of csPCa detection and obtained a DSC of 0.14 / 0.25 / 0.28.

Conclusion
The results show that the decision level fusion network performs better for the task of prostate lesion detection. Combining mpMRI data with quantitative clinical data does not show significant differences between these networks (p = 0.26/0.62/0.85). The results show that CNNs trained with all mpMRI data outperform CNNs with less input channels which is consistent with current clinical protocols where the same input is used for PI-RADS lesion scoring.

Trial registration
The trial was registered retrospectively at the German Register for Clinical Studies (DRKS) under proposal number Nr. 476/14 & 476/19.
CTSG may inhibit disease progression in HIV-related lung cancer patients by affecting immunosuppression
Authors: Yan Xuan , Wei Shuoyan , Yang Yuexiang , Zhao Zhangyan , Wu Qingguo , Tang Haicheng 
Published: July 2024

Abstract
Objectives
Lung cancer is an independent risk factor for pulmonary complications following HIV infection. This study aimed to examine the expression and clinical significance of Cathepsin G (CTSG) protein in both non-HIV and HIV-related lung cancers.

Methods
The data related to lung adenocarcinoma (LUAD) and lung squamous carcinoma (LUSC) in the TCGA dataset and the data related to healthy individuals in the GTEx dataset, the GEPIA2 database was used to excavate the distinction in the expression of CTSG protein in non-small cell lung cancer (NSCLC) tissues versus normal non-cancerous tissues. The Ualcan database was used to compare the differences in CTSG expression at different stages of LUAD and LUSC. Immunohistochemistry (IHC) was used to detect the expression of CTSG proteins in the pathological tissues of patients with HIV-related lung cancer and patients with lung cancer without co-infection, the Kaplan-Meier method was used for survival analysis.

Results
We observed that CTSG expression in NSCLC is lower compared to adjacent non-tumor tissues and correlates with NSCLC clinical stage. CTSG protein expression in HIV-related lung cancer tissues was lower than in adjacent tissues and lower than in lung cancer tissues without HIV infection, with a statistically significant difference (P < 0.05). It correlated with CD4 + T cell count and CD4+/CD8 + T cell ratio, as well as with the pathological type, distant metastasis, and clinical stage of HIV-related lung cancer, all with statistical significance (P < 0.05).

Conclusions
CTSG could potentially mitigate disease advancement in HIV-related lung cancer patients by inhibiting immune depletion, serving as a prospective immunotherapeutic target for both non-HIV and HIV-associated lung cancers.
Sharenting: characteristics and awareness of parents publishing sensitive content of their children on online platforms
Authors: Conti Maria Giulia , Del Parco Fabiola , Pulcinelli Francesca Maria , Mancino Enrica , Petrarca Laura , Nenna Raffaella , Di Mattia Greta , Matera Luigi , La Regina Domenico Paolo , Bonci Enea , Caruso Cinthia , Midulla Fabio 
Published: July 2024

Abstract
Background
The term “sharenting” describes the increasingly popular habit of parents to share photos, videos, or other information regarding their children on their social profiles, through online platforms. It is highly likely that many parents are posting content about their underage children online with little knowledge of the risks associated with this practice. This study aims to investigate whether variables such as parents’ age, gender, marital status, occupation and educational level influence the practice of sharing child-related content and the degree of awareness.

Methods
We performed a pilot cross-sectional study, based on an anonymous questionnaire. The questionnaire was administered to parents of underage children attending the pediatric outpatient clinic of the Umberto I Hospital, Sapienza University, in Rome, Italy, by researchers, through the google forms platform; qualitative variables were generated on excel sheets and a statistical analysis was performed on SPSS Ibm-statistics using the chi-square test.

Results
Two hundred twenty-eight parents of children under 18 years of age completed the questionnaire (82% mothers, 18% fathers); 98% of the respondents used social media and 75% of them published their children’s related content online. Thirty-one percent of the compilers started their practice of sharenting in the first 6 months of life of their child. Our analysis showed that compared to parents who do not post online, parents who usually post online their children are significantly more likely to be partial employees or unemployed (p = 0,002), with lower educational level (p = 0,05), younger (less than 35 years of age (p = 0,01)) and have a higher number of followers (p < 0,001). Finally, 93% of the compilers were not aware of the current legislation and of the risks related to the practice of sharenting.

Conclusions
Pediatricians, healthcare assistants and preventive healthcare professionals should play a central role in alerting parents and families to the risks of sharenting; the results of our study could draw their attention to the increasing practice of sharenting and make healthcare professionals active part in the protection of children.
Strain and model development for auto- and heterotrophic 2,3-butanediol production using Cupriavidus necator H16
Authors: Weiler Janek R. , Jürgensen Nikolai , Cornejo Infante Monica , Knoll Melanie T. , Gescher Johannes 
Published: July 2024

AbstractThe production of platform chemicals from renewable energy sources is a crucial step towards a post-fossil economy. This study reports on the production of acetoin and 2,3-butanediol heterotrophically with fructose as substrate and autotrophically from CO2 as carbon source, H2 as electron donor and O2 as electron acceptor with Cupriavidus necator. In a previous study, the strain was developed for the production of acetoin with high carbon efficiency. Acetoin can serve as a precursor for the synthesis of 2,3-butanediol by the integration of a butanediol dehydrogenase. In this study, different plasmid backbones and butanediol dehydrogenases were evaluated regarding efficiency for CO2-based 2,3-butanediol production. The developed strain utilizes the pBBR1 plasmid bearing a 2,3-butanediol dehydrogenase from Enterobacter cloacae and is characterized by 2,3-butanediol as the main product and a heterotrophic total product yield of 88.11%, an autotrophic volumetric productivity of 39.45 mg L−1 h−1, a total product carbon yield of 81.6%, an H2 efficiency of 33.46%, and a specific productivity of 0.016 g product per gram of biomass per hour. In addition, a mathematical model was developed to simulate the processes under these conditions. With this model, it was possible to calculate productivities and substrate usage at distinct time points of the production processes and calculate productivities and substrate usage with high resolution which will be useful in future applications.
Rapid and reliable detection of Leishmania antibodies in canine serum with double-antigen sandwich homogeneous chemical luminescence
Authors: Zhao Xiangjun , Ma Licai , Jin Yipeng , Barkema Herman W. , Kastelic John P. , Wang Lu , Wen Kai , Liu Gang 
Published: July 2024

AbstractBackgroundLeishmaniasis, caused byLeishmaniaspp. parasites, is an important zoonotic disease globally, posing severe threats to humans and animals. In the absence of effective vaccines, reliable serological diagnostic methods are critical for disease control. However, the enzyme-linked immunosorbent assay (ELISA) and immunochromatographic assay have limitations due to complexity, time required and/or sensitivity. Therefore, our objective was to develop an accurate, rapid and user-friendly detection method of canine leishmania antibody based on double-antigen sandwich homogeneous chemical luminescence.MethodsHomogeneous chemiluminescent technology was employed, and expressed recombinant fusion proteins containing full-length K9, K39 and K26 repeat sequences were used as diagnostic antigens. To establish a dual-antigen sandwich serological assay capable of detecting various antibody types, a factorial design was used to optimize concentrations of diagnostic antigen-receptor microspheres and of biotinylated diagnostic antigens, as well as of reaction solution composition and reaction duration. To evaluate and validate this newly developed method, we collected 41Leishmania-positive serum samples, 30Leishmania-negative control serum samples and 78 clinical serum samples for which no diagnostic information was available. Comparative analyses were performed using parasitological testing and an indirect ELISA as reference methods, focusing on diagnostic sensitivity and specificity.ResultsSodium dodecyl sulfate–polyacrylamide gel electrophoresis confirmed the purification of the diagnostic antigens, which exhibited clear bands without impurities. Based on results from the 41Leishmania-positive samples and 30Leishmania-negative samples, there was sufficient sensitivity to detect samples diluted up to 256-fold, with analytical specificity of 100%. Overall diagnostic sensitivity was 100% and diagnostic specificity was 93.3%. Diagnostic performance was highly consistent between the newly developed method and the indirect ELISA (Kappa = 0.82,P < 0.01). Testing could be completed within 35 min with the new methodConclusionsWe have developed a novel double-antigen sandwich homogeneous chemical luminescence method to detect canineLeishmaniaantibodies, with high sensitively and specificity, a short incubation interval and a simple protocol. This streamlined approach not only offers a sensitive and efficient method for clinical diagnosis but also has great potential for use in automated testing.Graphical Abstract
Expression of CD163 and major histocompatibility complex class I as diagnostic markers for idiopathic inflammatory myopathies
Authors: Ghang Byeongzu , Nam So Hye , Choi Wonho , Kim Hwa Jung , Lee Jungsun , Lim Doo-Ho , Ahn Soo Min , Oh Ji Seon , Hong Seokchan , Kim Yong-Gil , Lee Chang-Keun , Kim Jinseok , Yoo Bin , Nam Soo Jeong 
Published: July 2024

Abstract
Background
To develop an inflammation-related immunohistochemistry marker-based algorithm that confers higher diagnostic ability for idiopathic inflammatory myopathies (IIMs) than IIM-related histopathologic features.

Methods
Muscle biopsy tissues from 129 IIM patients who met the 2017 EULAR/ACR criteria and 73 control tissues from patients with non-inflammatory myopathies or healthy muscle specimens were evaluated for histological features and immunostaining results of CD3, CD4, CD8, CD20, CD68, CD163, MX1, MHC class I, MHC class II, and HLA-DR. Diagnostic algorithms for IIM were developed based on the results of the classification and regression tree (CART) analysis, which used immunostaining results as predictor variables for classifying patients with IIMs.

Results
In the analysis set (IIM, n = 129; control, n = 73), IIM-related histopathologic features had a diagnostic accuracy of 87.6% (sensitivity 80.6%; specificity 100.0%) for IIMs. Notably, muscular expression of CD163 (99.2% vs. 20.8%, p < 0.001) and MHC class I (87.6% vs. 23.1%, p < 0.001) was significantly higher in the IIM group than in controls. Based on the CART analysis results, we developed an algorithm combining CD163 and MHC class I expression that conferred a diagnostic accuracy of 95.5% (sensitivity 96.1%; specificity 94.5%). In addition, our algorithm was able to correctly diagnose IIM in 94.1% (16/17) of patients who did not meet the 2017 EUALR/ACR criteria but were diagnosed as having IIMs by an expert physician.

Conclusions
Combination of CD163 and MHC class I muscular expression may be useful in diagnosing IIMs.