bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evaluasi Kesesuaian Lahan untuk Tanaman Jagung (Zea mays L.) di Kecamatan Dulupi Kabupaten Boalemo
Authors: Mobilingo Sinta , Nurdin Nurdin, M.Si , Zakaria Fauzan 
Published: January 2024

Dulupi is one of the districts in Boalemo Regency which is a center for maize production, but the high intensity of maize cultivation causes a decrease in the quality of the local land. This research aimed to determine the land suitability classes and limiting factor for maize (Zea mays L.). The research was carried out in Dulupi District of Boalemo Regency from September to Desember 2022. It employed a data matching method, matching the data for each land unit with suitability criteria. The findings revealed that the level of the land suitability for maize in Dulupi District, Boalemo Regency had theree classes of land suitability, namely moderately suitable (S2) of 88% (6314,54 Ha), marginally suitable (S3) of 10% (763,89 Ha), and not suitable (N) of 2% (41,15 Ha). In contrast, the yield-limiting factors were nutrient retention, avaible nutriens (N, P, K), erosion hazard, drainage, and effetive depth. With the improvment efforts, the yield limiting factors in the potential land and suitability increased to S2 and S3 classes.
KEPUASAN KONSUMEN MUDA TERHADAP DESAIN KEMASAN BERAS ORGANIK DI INDONESIA
Authors: Prasetyo Agung , Supriyadi Teguh , Suryaningsih Agustina Tri 
Published: January 2024

Pengembangan produk beras organik penting untuk menarik konsumen muda untuk membeli dan mengonsumsi. Saat membeli produk, pengemasan adalah daya tarik terpenting bagi konsumen. Selain itu, konsumen juga menginginkan bentuk kemasan yang menjaga produk dalam kondisi baik. Tujuan dari penelitian ini adalah untuk menentukan kepuasan konsumen muda terhadap kemasan beras organik di Indonesia. Penelitian dilakukan di berbagai kota Indonesia seperti Jakarta, Semarang, Jogjakarta, Bojonegoro, Kotawaringin Barat, penajam paser utara dan Soloraya dengan responden konsumen beras organik pada usia 17-35 tahun. Data dianalisis menggunakan analisis CSI (Customer Satisfaction Index). Hasil temuan menunjukan bahwa kepuasan konsumen muda terhadap atribut kemasan beras organik di Indonesia tergolong sangat puas. Estetika kemasan menjadi atribut yang harus mendapatkan perhatian untuk ditingkatkan agar dapat meningkatkan kepuasan konsumen dalam berbelanja.
Sustainable Concrete: Exploring Fresh, Mechanical, Durability, and Microstructural Properties with Recycled Fine Aggregates
Authors: Panghal Harish , Kumar Awadhesh 
Published: January 2024

The growing construction industry and global population have led to increased demand for concrete, resulting in increased waste production. Recycling construction and demolition (C&D) waste as recycled fine aggregates (RFA) in concrete could help reduce waste and conserve natural resources. This research delves into the meticulous examination of particle packing density within specific cylindrical volumes under standard compacting efforts, elucidating an order of compressive strength. The study comprehensively explores various concrete properties, including workability, compressive strength, flexural strength, split tensile strength, drying shrinkage, electrical resistivity, rapid chloride penetration, and microstructural characteristics (analyzed through XRD, SEM, and EDAX). RFA particles, ranging from 0.15 to 4.75 mm, were employed as partial replacements for fine aggregates, with replacement percentages varying from 0% to 100% in increments of 25%. The empirical findings underscore that the incorporation of RFA significantly enhances concrete properties. However, it was observed that surpassing the optimum replacement percentage of 25% (RFA 25) adversely impacts the concrete’s strength and microstructure. Specifically, RFA 25 exhibited remarkable improvements, with a 14.75% increase in compressive strength, a 6.61% boost in flexural strength, and a 13.14% enhancement in split tensile strength compared to conventional concrete (RC). Furthermore, RFA 25 demonstrated a 4.16% increment in drying shrinkage, 17.65% higher electrical resistivity, and an 18.83% superior resistance to chloride penetration compared to RC. The analysis of XRD, SEM, and EDAX results elucidated that at lower replacement percentages, the pozzolanic reaction enhances strength by forming additional hydration products. Conversely, at higher replacement levels, strength diminishes.
Longitudinal phase 2 clinical trials of live, attenuated tularemia vaccine in healthy research laboratory workers
Authors: Saunders David L. , Pierson Benjamin C. , Haller Jeannine , Norris Sarah , Cardile Anthony P. , Reisler Ronald B. , Okwesili Arthur C. , Boudreau Ellen , Rusnak Janice , Danner Denise K. , Purcell Bret K. , Barth James F. , Tompkins Erin L. , Downs Isaac L. , Liggett Dani , Pettit Patricia , Pratt Tami , Goldberg Mark , Kortepeter Mark G. , Guerena Fernando B. , Aldis John W. , Keshtkar-Jahromi Maryam , Pittman Phillip R. 
Published: January 2024

BackgroundTularemia is caused by the intracellular bacterium Francisella tularensis (Ft). It was weaponized historically due to low infectious aerosol dose, high morbidity, and mortality rates for pneumonic disease. The US Army developed the attenuated Live Vaccine Strain (LVS) from stocks provided by the former Soviet Union in the 1950s. The vaccine has been safe and immunogenic over the ensuing decades in multiple clinical trials including human challenge studies.MethodsTwo sequential FDA-regulated, non-randomized, single-arm LVS trials enrolled at-risk laboratory personnel working on tularemia in bio-containment laboratories under IND#157. Volunteers received a single dose of LVS manufactured in 1962 by scarification. Positive immunization was based on local scarification site “take reaction,” and either a &gt;1:20 tularemia antigen microagglutination (MA) titer (protocol FY03-24; 2004-8) or &gt;4-fold rise in MA titer (protocol FY07-15; 2009-2017). Those still negative by week 4 were offered a second dose.ResultsThe LVS vaccine was safe, well tolerated, and highly immunogenic. Between the two studies, all recipients (100%) had positive “take reactions,” with 95.5% of those in study FY03-24 having a positive response following initial vaccination. All but three subjects (98%) in protocol FY03-24 had positive MA titer results defined as &gt;1:20, most within 28–35 days. In protocol FY07-15, 95% of subjects had a 4-fold or greater rise in MA titer, the primary immunogenicity endpoint for that study.DiscussionLVS vaccine administered to laboratory workers at risk for tularemia exposure over 12 years was safe and highly immunogenic. Response rates remained robust despite the vaccine lots employed having been manufactured 42–55 years prior to vaccination. The results and historical comparator data presented here serve as a benchmark for future studies. LVS remains unlicensed due to instability in culture and the potential for reversion to the wild-type pathogen. Despite the threat, there are no FDA-approved vaccines. In the absence of a clinical-stage commercial development effort, an ongoing LVS vaccine protocol under investigational new drug (IND) application for at-risk laboratory workers to prevent occupationally acquired disease should be considered based on extensive favorable data for this vaccine.Clinical trial registrationClinicalTrials.gov, identifiers NCT00584844 (trial FY03-24) and NCT00787826 (trial FY07-15).
Quantitative and qualitative initial validation of the accountable talk questionnaire
Authors: Kofman Talmy Ayelet , Mashal Nira 
Published: January 2024

IntroductionAccountable Talk (AT) has been extensively studied as a tool for improving argumentation and respectful discourse. While several research tools exist for evaluating AT, as of yet there no self-report assessment tool to measure AT directly, on a large-scale basis, and without significant costs. The aim of the current study was to develop and provide initial validation for a self-report AT questionnaire (ATQ).MethodsOne hundred students aged 11–12 years participated in the study. Exploratory Factor Analysis, content validity, and test- retest reliability were assessed. 50 students were also randomly assigned to the qualitative part of the study. These students were recorded while discussing in small groups a topic provided by the experimenter (animal research). The qualitative data was coded and then correlated with the quantitative data obtained from the self-report questionnaire.ResultsThe results indicated that a 12-items questionnaire can reliably assess three separate and independent qualities of AT: accountability to a learning community, accountability to rigorous thinking, and accountability to accurate knowledge. The reliability of the ATQ was high with α = 0.80. The Test-retest reliability was assessed at two time points separated by a 3-week interval with Pearson correlation. Excellent correlations (r &gt; 0.98) between the ATQ scores were found. The correlation coefficients between the three components of the self-reported ATQ and the observed data obtained from the group discussions were significant positive medium-high.DiscussionWe have shown that a concise 12-item questionnaire can assess the three main components of Accountable Talk within the framework of respectful discourse. The questionnaire showed good reliability and structural validity, with weak correlations between sub-topics supporting the distinction between different aspects of Accountable Talk. We suggest that the ATQ can be used to evaluate the effectiveness of intervention programs aiming to improve students' acquisition of Accountable Talk skills.
Associations of antidiabetic drugs with diabetic retinopathy in people with type 2 diabetes: an umbrella review and meta-analysis
Authors: Tan Luyuan , Wang Zhaonan , Okoth Kelvin , Toulis Konstantinos A. , Denniston Alastair K. , Singh Baldev M. , Crowe Francesca L. , Sainsbury Christopher , Wang Jingya , Nirantharakumar Krishnarajah 
Published: January 2024

BackgroundDiabetic retinopathy (DR) is the most frequent complication of type 2 diabetes and remains the leading cause of preventable blindness. Current clinical decisions regarding the administration of antidiabetic drugs do not sufficiently incorporate the risk of DR due to the inconclusive evidence from preceding meta-analyses. This umbrella review aimed to systematically evaluate the effects of antidiabetic drugs on DR in people with type 2 diabetes.MethodsA systematic literature search was undertaken in Medline, Embase, and the Cochrane Library (from inception till 17th May 2022) without language restrictions to identify systematic reviews and meta-analyses of randomized controlled trials or longitudinal studies that examined the association between antidiabetic drugs and DR in people with type 2 diabetes. Two authors independently extracted data and assessed the quality of included studies using the AMSTAR-2 (A MeaSurement Tool to Assess Systematic Reviews) checklist, and evidence assessment was performed using the GRADE (Grading of recommendations, Assessment, Development and Evaluation). Random-effects models were applied to calculate relative risk (RR) or odds ratios (OR) with 95% confidence intervals (CI). This study was registered with PROSPERO (CRD42022332052).ResultsWith trial evidence from 11 systematic reviews and meta-analyses, we found that the use of glucagon-like peptide-1 receptor agonists (GLP-1 RA), sodium-glucose cotransporter-2 inhibitors (SGLT-2i), or dipeptidyl peptidase-4 inhibitors (DPP-4i) was not statistically associated with the risk of DR, compared to either placebo (RR: GLP-1 RA, 0.98, 0.89-1.08; SGLT-2i, 1.00, 95% CI 0.79-1.27; DPP-4i, 1.17, 0.99-1.39) or other antidiabetic drugs. Compared to other antidiabetic drugs, meglitinides (0.34, 0.01-8.25), SGLT-2i (0.73, 0.10-5.16), thiazolidinediones (0.92, 0.67-1.26), metformin (1.15, 0.81-1.63), sulphonylureas (1.24, 0.93-1.65), and acarbose (4.21, 0.44-40.43) were not statistically associated with the risk of DR. With evidence from longitudinal studies only, insulin was found to have a higher risk of DR than other antidiabetic drugs (OR: 2.47, 95% CI: 2.04-2.99).ConclusionOur results indicate that antidiabetic drugs are generally safe to prescribe regarding the risk of DR among people with type 2 diabetes. Further robust and large-scale trials investigating the effects of insulin, meglitinides, and acarbose on DR are warranted.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/display_record.php?RecordID=332052, identifier CRD42022332052.
A study of the relationship between cytokine levels and the response to anti-VEGF therapy in polypoid choroidal vasculopathy with different choroidal thicknesses
Authors: Dong Su , Fan Pan , Yu Haotian , Jiang Bo , Sun Dawei 
Published: January 2024

PurposePolypoidal choroidal vasculopathy (PCV) is an irreversible retinal choroidal disease. Individuals with PCV exhibit diverse baseline characteristics, including systemic characteristics, ocular traits, metabolic factor levels, and different responses to intravitreal anti-VEGF therapy. This study aims to investigate the pathogenesis of PCV by analyzing the systemic characteristics, ocular traits, and cytokine levels at baseline within a cohort of patients who exhibit different responses to anti-VEGF treatment.MethodsWe conducted a retrospective analysis involving 80 eyes diagnosed with PCV. Patients were categorized into two groups based on responses to suboptimal intravitreal ranibizumab injection therapy: those with suboptimal responses and optimal responses. Aqueous humor samples were collected from the experimental eyes, and cytokine expression levels were assessed using cytometric bead array analysis. All subjects were further stratified into two groups according to the median choroidal thickness. Subsequently, logistic regression analysis and the ROC curve were employed to examine the relationship between cytokine expression levels, choroidal thickness, and anti-VEGF response.ResultsThe results revealed that compared to the group of optimal anti-VEGF response, the choroid in the suboptimal response group exhibited a significantly greater thickness. Additionally, compared to the suboptimal anti-VEGF response group, the expression levels of VEGF and VCAM-1 were markedly lower observed in the optimal anti-VEGF response group, while TNF-α showed the opposite trend. Logistic regression analysis indicated that VEGF, VCAM-1, and TNF-α in the aqueous humor were independent risk factors for a suboptimal anti-VEGF response. After adjusting other risk factors, the risk of suboptimal anti-VEGF response decreased to 0.998-fold, 0.997-fold, and 1.294-fold. The AUC values for VEGF, VCAM-1, and TNF-α were determined to be 0.805, 0.846, and 0.897, respectively. Furthermore, the risk of VEGF, VCAM-1, and TNF-α were significantly associated with an increased risk of suboptimal anti-VEGF response after correction for risk factors in the thick choroid group.ConclusionsOur study demonstrated that PCV exhibits systemic and ocular characteristics variations based on different anti-VEGF responses. The levels of cytokines in aqueous humor were found to have a significant correlation with the anti-VEGF response in PCV. VEGF, VCAM-1, and TNF-α are potential targets for assessing treatment response in thick choroidal PCV.
Platelet derived exosomes disrupt endothelial cell monolayer integrity and enhance vascular inflammation in dengue patients
Authors: Vedpathak Sayali , Sharma Archana , Palkar Sonali , Bhatt Varsha R. , Patil Vishwanath Chandrashekhar , Kakrani Arjun L. , Mishra AkhileshChandra , Bhosle Deepak , Arankalle Vidya A. , Shrivastava Shubham 
Published: January 2024

BackgroundThrombocytopenia is the most notable phenomenon in dengue. Activation status of platelets and interaction of platelets with endothelium contribute towards dengue disease pathogenesis. Platelets are the major cell types known to release extracellular vesicles, especially exosomes in circulation. However, the role of platelet derived exosomes (PLT-EXOs) in endothelial dysfunction during dengue infection remains unknown.MethodsIn this study, we recruited 28 healthy subjects and 69 dengue patients categorized as WS- (n=31), WS+ (n=29) and SD (n=9). Platelets were isolated from platelet rich plasma of dengue patients and their activation was assessed by flow cytometry. PLT-EXOs were isolated by ultracentrifugation method. Western blot analyses were performed to characterize the exosomes. Exosome uptake experiment was carried out to see the internalization of exosomes inside endothelial cells (HUVECs). To observe the effect of exosomes on endothelial cells, exosomes were added on HUVECs and expression of adherens and tight junctional proteins were examined by immunofluorescence assay and western blot. Expression levels of vascular injury markers were measured in the culture supernatants of Exosome-HUVEC coculture and sera of dengue patients by MSD-multiplex assay.ResultsAs compared to healthy subjects, CD41/CD61 expression was significantly reduced (p&lt;0.0001) and CD62p expression was significantly increased (p&lt;0.0001) on platelets in dengue patients. PLT-EXOs isolated from the dengue patients showed higher expression of CD63 and CD9 proteins than the healthy subjects. With in-vitro immunofluorescence assays, we illustrated the internalization of PLT-EXOs by the HUVECs and observed disruption of endothelial cell monolayer integrity in the presence of PLT-EXOs from WS+ and SD patients. Furthermore, the significant reduction in the expressions of ZO-2, VE-Cadherin and CD31 in endothelial cells following exposure to PLT-EXOs from the dengue patients provide direct evidence of PLT-EXOs mediated vascular permeability. PLT-EXOs stimulated the release of inflammatory markers CRP, SAA, sVCAM-1 and sICAM-1 in the supernatants of HUVEC cells. Importantly, significantly higher levels of CRP, sVCAM-1 and sICAM-1 in the sera of severe than mild dengue patients (p&lt;0.0001) suggest their role in disease severity.ConclusionsIn summary, our data suggest that PLT-EXOs promote vascular leakage via release of proinflammatory mediators and compromise vascular barrier integrity in dengue patients.
Integrating single-cell and bulk transcriptomic analyses to develop a cancer-associated fibroblast-derived biomarker for predicting prognosis and therapeutic response in breast cancer
Authors: Li Chunzhen , Yang Lanjie , Zhang Yunyan , Hou Qianshan , Wang Siyi , Lu Shaoteng , Tao Yijie , Hu Wei , Zhao Liyuan 
Published: January 2024

BackgroundCancer-associated fibroblasts (CAFs) contribute to the progression and treatment of breast cancer (BRCA); however, risk signatures and molecular targets based on CAFs are limited. This study aims to identify novel CAF-related biomarkers to develop a risk signature for predicting the prognosis and therapeutic response of patients with BRCA.MethodsCAF-related genes (CAFRGs) and a risk signature based on these genes were comprehensively analyzed using publicly available bulk and single-cell transcriptomic datasets. Modular genes identified from bulk sequencing data were intersected with CAF marker genes identified from single-cell analysis to obtain reliable CAFRGs. Signature CAFRGs were screened via Cox regression and least absolute shrinkage and selection operator (LASSO) analyses. Multiple patient cohorts were used to validate the prognosis and therapeutic responsiveness of high-risk patients stratified based on the CAFRG-based signature. In addition, the relationship between the CAFRG-based signature and clinicopathological factors, tumor immune landscape, functional pathways, chemotherapy sensitivity and immunotherapy sensitivity was examined. External datasets were used and sample experiments were performed to examine the expression pattern of MFAP4, a key CAFRG, in BRCA.ResultsIntegrated analyses of single-cell and bulk transcriptomic data as well as prognostic screening revealed a total of 43 prognostic CAFRGs; of which, 14 genes (TLN2, SGCE, SDC1, SAV1, RUNX1, PDLIM4, OSMR, NT5E, MFAP4, IGFBP6, CTSO, COL12A1, CCDC8 and C1S) were identified as signature CAFRGs. The CAFRG-based risk signature exhibited favorable efficiency and accuracy in predicting survival outcomes and clinicopathological progression in multiple BRCA cohorts. Functional enrichment analysis suggested the involvement of the immune system, and the immune infiltration landscape significantly differed between the risk groups. Patients with high CAF-related risk scores (CAFRSs) exhibited tumor immunosuppression, enhanced cancer hallmarks and hyposensitivity to chemotherapy and immunotherapy. Five compounds were identified as promising therapeutic agents for high-CAFRS BRCA. External datasets and sample experiments validated the downregulation of MFAP4 and its strong correlation with CAFs in BRCA.ConclusionsA novel CAF-derived gene signature with favorable predictive performance was developed in this study. This signature may be used to assess prognosis and guide individualized treatment for patients with BRCA.
The regulatory role of eosinophils in adipose tissue depends on autophagy
Authors: Hosseini Aref , Germic Nina , Markov Nikita , Stojkov Darko , Oberson Kevin , Yousefi Shida , Simon Hans-Uwe 
Published: January 2024

IntroductionObesity is a metabolic condition that elevates the risk of all-cause mortality. Brown and beige adipose tissues, known for their thermogenic properties, offer potential therapeutic targets for combating obesity. Recent reports highlight the role of immune cells, including eosinophils, in adipose tissue homeostasis, while the underlying mechanisms are poorly understood.MethodsTo study the role of autophagy in eosinophils in this process, we used a genetic mouse model lacking autophagy-associated protein 5 (Atg5), specifically within the eosinophil lineage (Atg5eoΔ).ResultsThe absence of Atg5 in eosinophils led to increased body weight, impaired glucose metabolism, and alterations in the cellular architecture of adipose tissue. Our findings indicate that Atg5 modulates the functional activity of eosinophils within adipose tissue rather than their abundance. Moreover, RNA-seq analysis revealed upregulation of arginase 2 (Arg2) in Atg5-knockout eosinophils. Increased Arg2 activity was shown to suppress adipocyte beiging. Furthermore, we observed enrichment of the purine pathway in the absence of Atg5 in eosinophils, leading to a pro-inflammatory shift in macrophages and a further reduction in beiging.DiscussionThe data shed light on the importance of autophagy in eosinophils and its impact on adipose tissue homeostasis by suppressing Arg2 expression and limiting inflammation in adipose tissue.