bluuebunny/crossref_metadata_2025_split huggingface dataset:
Factors associated with delaying medical care: cross-sectional study of Nebraska adults
Authors: Ratnapradipa Kendra L. , Jadhav Snehal , Kabayundo Josiane , Wang Hongmei , Smith Lisa C. 
Published: February 2023

Abstract
Background
Delayed medical care may result in adverse health outcomes and increased cost. Our purpose was to identify factors associated with delayed medical care in a primarily rural state.

Methods
Using a stratified random sample of 5,300 Nebraska households, we conducted a cross-sectional mailed survey with online response option (27 October 2020 to 8 March 2021) in English and Spanish. Multiple logistic regression models calculated adjusted odds ratios (aOR) and 95% confidence intervals.

Results
The overall response rate was 20.8% (n = 1,101). Approximately 37.8% of Nebraskans ever delayed healthcare (cost-related 29.7%, transportation-related 3.7%), with 22.7% delaying care in the past year (10.1% cost-related). Cost-related ever delay was associated with younger age [< 45 years aOR 6.17 (3.24–11.76); 45–64 years aOR 2.36 (1.29–4.32)], low- and middle-income [< $50,000 aOR 2.85 (1.32–6.11); $50,000-$74,999 aOR 3.06 (1.50–6.23)], and no health insurance [aOR 3.56 (1.21–10.49)]. Transportation delays were associated with being non-White [aOR 8.07 (1.54–42.20)], no bachelor’s degree [≤ high school aOR 3.06 (1.02–9.18); some college aOR 4.16 (1.32–13.12)], and income < $50,000 [aOR 8.44 (2.18–32.63)]. Those who did not have a primary care provider were 80% less likely to have transportation delays [aOR 0.20 (0.05–0.80)].

Conclusions
Delayed care affects more than one-third of Nebraskans, primarily due to financial concerns, and impacting low- and middle-income families. Transportation-related delays are associated with more indicators of low socio-economic status. Policies targeting minorities and those with low- and middle-income, such as Medicaid expansion, would contribute to addressing disparities resulting from delayed care.
Small-scale field evaluation of transfluthrin-treated eave ribbons and sandals for the control of malaria vectors in rural Tanzania
Authors: Mmbando Arnold S. , Mponzi Winifrida P. , Ngowo Halfan S. , Kifungo Khamis , Kasubiri Robert , Njalambaha Rukiyah M. , Gavana Tegemeo , Eiras Alvaro E. , Batista Elis P. A. , Finda Marceline F. , Sangoro Onyango P. , Okumu Fredros O. 
Published: February 2023

Abstract
Background
Early-evening and outdoor-biting mosquitoes may compromise the effectiveness of frontline malaria interventions, notably insecticide-treated nets (ITNs). This study aimed to evaluate the efficacy of low-cost insecticide-treated eave ribbons and sandals as supplementary interventions against indoor-biting and outdoor-biting mosquitoes in south-eastern Tanzania, where ITNs are already widely used.

Methods
This study was conducted in three villages, with 72 households participating (24 households per village). The households were divided into four study arms and assigned: transfluthrin-treated sandals (TS), transfluthrin-treated eave ribbons (TER), a combination of TER and TS, or experimental controls. Each arm had 18 households, and all households received new ITNs. Mosquitoes were collected using double net traps (to assess outdoor biting), CDC light traps (to assess indoor biting), and Prokopack aspirators (to assess indoor resting). Protection provided by the interventions was evaluated by comparing mosquito densities between the treatment and control arms. Additional tests were done in experimental huts to assess the mortality of wild mosquitoes exposed to the treatments or controls.

Results
TERs reduced indoor-biting, indoor-resting and outdoor-biting Anopheles arabiensis by 60%, 73% and 41%, respectively, while TS reduced the densities by 18%, 40% and 42%, respectively. When used together, TER & TS reduced indoor-biting, indoor-resting and outdoor-biting An. arabiensis by 53%, 67% and 57%, respectively. Protection against Anopheles funestus ranged from 42 to 69% with TER and from 57 to 74% with TER & TS combined. Mortality of field-collected mosquitoes exposed to TER, TS or both interventions was 56–78% for An. arabiensis and 47–74% for An. funestus.

Conclusion
Transfluthrin-treated eave ribbons and sandals or their combination can offer significant household-level protection against malaria vectors. Their efficacy is magnified by the transfluthrin-induced mortality, which was observed despite the prevailing pyrethroid resistance in the study area. These results suggest that TER and TS could be useful supplementary tools against residual malaria transmission in areas where ITN coverage is high but additional protection is needed against early-evening and outdoor-biting mosquitoes. Further research is needed to validate the performance of these tools in different settings, and assess their long-term effectiveness and feasibility for malaria control.
The significance of ophthalmological features in diagnosis of thyroid-associated ophthalmopathy
Authors: Huang Xiao , Tang Wei , Shen Ya , He Linfeng , Tong Fei , Liu Siyu , Li Jian , Li Pan , Zhang Yun , Ma Xiaoye , Wei Ruili , Yang Weihua 
Published: February 2023

Abstract
Background
Thyroid-associated ophthalmopathy (TAO) is an autoimmune disorder. It has discriminable appearance. This study was conducted to dig the clinical significance of demographic characteristics and ophthalmologic diagram features in TAO diagnosis and stage/severity evaluation.

Results
We included 320 males and 633 females, with an average age of 41.75 ± 13.75. A majority of TAO patients had hyperthyroidism, and most of them were in the inactive stage and at the moderate level. The thyroid function type, stage and severity were closely associated with hypopsia, eyelid congestion, conjunctival congestion, corneal ulcer, ocular motility disorder, best corrected visual acuity, and extraocular muscle thickening. Using these features, we established different logistic regression models to predict thyroid function subtypes, abnormal thyroid function, stage, and severity, in which the AUC of the ROC curve and accuracies were satisfactory.

Conclusion
Together, TAO subtype, stage and severity can be diagnosed by auxiliary references including demographic factors, symptoms from complains, and image features. These non-invasive indices can be applied in a timely manner in clinical estimating TAO status.
Regulatory cells and the effect of cancer immunotherapy
Authors: Iglesias-Escudero María , Arias-González Noelia , Martínez-Cáceres Eva 
Published: February 2023

AbstractSeveral mechanisms and cell types are involved in the regulation of the immune response. These include mostly regulatory T cells (Tregs), regulatory macrophages (Mregs), myeloid suppressor cells (MDSCs) and other regulatory cell types such as tolerogenic dendritic cells (tolDCs), regulatory B cells (Bregs), and mesenchymal stem cells (MSCs). These regulatory cells, known for their ability to suppress immune responses, can also suppress the anti-tumor immune response. The infiltration of many regulatory cells into tumor tissues is therefore associated with a poor prognosis. There is growing evidence that elimination of Tregs enhances anti-tumor immune responses. However, the systemic depletion of Treg cells can simultaneously cause deleterious autoimmunity. Furthermore, since regulatory cells are characterized by their high level of expression of immune checkpoints, it is also expected that immune checkpoint inhibitors perform part of their function by blocking these molecules and enhancing the immune response. This indicates that immunotherapy does not only act by activating specific effector T cells but can also directly or indirectly attenuate the suppressive activity of regulatory cells in tumor tissues. This review aims to draw together our current knowledge about the effect of immunotherapy on the various types of regulatory cells, and how these effects may be beneficial in the response to immunotherapy.
Letter to the Editor: clinical utility of urine DNA for noninvasive detection and minimal residual disease monitoring in urothelial carcinoma
Authors: Yang Kaiwei , Hu Hailong , Wu Junlong , Wang Huina , Guo Zhaoxia , Yu Wei , Yao Lin , Ding Feng , Zhou Tao , Wang Wang , Wang Yunkai , Liu Lei , Guo Jing , Zhu Shuaipeng , Zhang Xinhao , Cao Shanbo , Lou Feng , Niu Yuanjie , Ye Dingwei , He Zhisong 
Published: February 2023

AbstractCurrent methods for the early detection and minimal residual disease (MRD) monitoring of urothelial carcinoma (UC) are invasive and/or possess suboptimal sensitivity. We developed an efficient workflow named urine tumor DNA multidimensional bioinformatic predictor (utLIFE). Using UC-specific mutations and large copy number variations, the utLIFE-UC model was developed on a bladder cancer cohort (n = 150) and validated in The Cancer Genome Atlas (TCGA) bladder cancer cohort (n = 674) and an upper tract urothelial carcinoma (UTUC) cohort (n = 22). The utLIFE-UC model could discriminate 92.8% of UCs with 96.0% specificity and was robustly validated in the BLCA_TCGA and UTUC cohorts. Furthermore, compared to cytology, utLIFE-UC improved the sensitivity of bladder cancer detection (p < 0.01). In the MRD cohort, utLIFE-UC could distinguish 100% of patients with residual disease, showing superior sensitivity compared to cytology (p < 0.01) and fluorescence in situ hybridization (FISH, p < 0.05). This study shows that utLIFE-UC can be used to detect UC with high sensitivity and specificity in patients with early-stage cancer or MRD. The utLIFE-UC is a cost-effective, rapid, high-throughput, noninvasive, and promising approach that may reduce the burden of cystoscopy and blind surgery.
Multi-level influences on increased overdose risk behaviors during the COVID-19 pandemic among people who use drugs in Rhode Island: a qualitative investigation
Authors: Frueh Lisa , Collins Alexandra B. , Newman Roxxanne , Barnett Nancy P. , Rich Josiah D. , Clark Melissa A. , Marshall Brandon D. L. , Macmadu Alexandria 
Published: February 2023

AbstractBackgroundThe ongoing COVID-19 pandemic has disproportionately affected structurally vulnerable populations including people who use drugs (PWUD). Increased overdose risk behaviors among PWUD during the pandemic have been documented, with research underscoring the role of influencing factors such as isolation and job loss in these behaviors. Here, we use qualitative methods to examine the impact of the COVID-19 pandemic and pandemic-related response measures on drug use behaviors in a sample of PWUD in Rhode Island. Using a social-ecological framework, we highlight the nested, interactive levels of the pandemic’s influence on increased overdose risk behaviors.MethodsFrom July to October 2021, semi-structured interviews were conducted with 18 PWUD who self-reported any increase in behaviors associated with overdose risk (e.g., increased use, change in drug type and/or more solitary drug use) relative to before the pandemic. Thematic analysis was conducted using a codebook with salient themes identified from interview guides and those that emerged through close reading of transcribed interviews. Guided by a social-ecological framework, themes were grouped into individual, network, institutional, and policy-level influences of the pandemic on drug use behaviors.ResultsIndividual-level influences on increased overdose risk behaviors included self-reported anxiety and depression, isolation and loneliness, and boredom. Network-level influences included changes in local drug supply and changes in social network composition specific to housing. At the institutional level, drug use patterns were influenced by reduced access to harm reduction or treatment services. At the policy level, increased overdose risk behaviors were related to financial changes, job loss, and business closures. All participants identified factors influencing overdose risk behaviors that corresponded to several nested social-ecological levels.ConclusionsParticipants identified multi-level influences of the COVID-19 pandemic and pandemic-related response measures on their drug use behavior patterns and overdose risk. These findings suggest that effective harm reduction during large-scale crises, such as the COVID-19 pandemic, must address several levels of influence concurrently.
Prognostic value of the pretreatment systemic immune-inflammation index in patients with prostate cancer: a systematic review and meta-analysis
Authors: Meng Linghao , Yang Yujia , Hu Xu , Zhang Ruohan , Li Xiang 
Published: February 2023

Abstract
Background
The systemic immune-inflammation index (SII) is a novel biomarker to predict the prognosis of some malignant tumors based on neutrophil, platelet, and lymphocyte counts. Evidence is scarce about the prognostic value of SII for prostate cancer patients. This systematic review and meta-analysis was conducted to explore the prognostic value of the SII in prostate cancer.

Methods
The PubMed, Embase, Web of Science, and Cochrane Library (CENTRAL) databases were searched to determine eligible studies from inception to August 15, 2022. Hazard ratios (HRs) with 95% confidence intervals (CIs) were extracted to pool the results. Statistical analyses were conducted by using Stata 17.0 software.

Results
A total of 12 studies with 8083 patients were included. The quantitative synthesis showed that a high SII was related to poor overall survival (OS) (HR = 1.44, 95% CI 1.23–1.69, p < 0.001). Furthermore, a subgroup analysis showed that a high SII was associated with poor OS in the groups of any ethnicity, tumor type, and cutoff value. An increased SII was also associated with inferior progression-free survival (PFS) (HR = 1.80, 95% CI 1.27–2.56, p = 0.001). In the subgroup analysis, a high SII value was related to poor PFS in Asian patients (HR = 4.03, 95% CI 1.07–15.17, p = 0.04) and a cutoff value > 580 (HR = 1.19, 95% CI 1.04–1.36, p = 0.01).

Conclusion
Based on the current evidence, a high pretreatment SII may be associated with poor OS and PFS. The SII may serve as an important prognostic indicator in patients with prostate cancer. More rigorously designed studies are needed to explore the SII and the prognosis of prostate cancer.
Endothelial Toll-like receptor 4 is required for microglia activation in the murine retina after systemic lipopolysaccharide exposure
Authors: Tsioti Ioanna , Steiner Beatrice L. , Escher Pascal , Zinkernagel Martin S. , Benz Peter M. , Kokona Despina 
Published: February 2023

Abstract
Background
Clustering of microglia around the vasculature has been reported in the retina and the brain after systemic administration of lipopolysaccharides (LPS) in mice. LPS acts via activation of Toll-like receptor 4 (TRL4), which is expressed in several cell types including microglia, monocytes and vascular endothelial cells. The purpose of this study was to investigate the effect of systemic LPS in the pigmented mouse retina and the involvement of endothelial TLR4 in LPS-induced retinal microglia activation.

Methods
C57BL/6J, conditional knockout mice that lack Tlr4 expression selectively on endothelial cells (TekCre−posTlr4loxP/loxP) and TekCre−negTlr4loxP/loxP mice were used. The mice were injected with 1 mg/kg LPS via the tail vein once per day for a total of 4 days. Prior to initiation of LPS injections and approximately 5 h after the last injection, in vivo imaging using fluorescein angiography and spectral-domain optical coherence tomography was performed. Immunohistochemistry, flow cytometry, electroretinography and transmission electron microscopy were utilized to investigate the role of endothelial TLR4 in LPS-induced microglia activation and retinal function.

Results
Activation of microglia, infiltration of monocyte-derived macrophages, impaired ribbon synapse organization and retinal dysfunction were observed after the LPS exposure in C57BL/6J and TekCre−negTlr4loxP/loxP mice. None of these effects were observed in the retinas of conditional Tlr4 knockout mice after the LPS challenge.

Conclusions
The findings of the present study suggest that systemic LPS exposure can have detrimental effects in the healthy retina and that TLR4 expressed on endothelial cells is essential for retinal microglia activation and retinal dysfunction upon systemic LPS challenge. This important finding provides new insights into the role of microglia–endothelial cell interaction in inflammatory retinal disease.
Deciphering the protective effect of Buzhong Yiqi Decoction on osteoporotic fracture through network pharmacology and experimental validation
Authors: Hua Zhen , Dai Shijie , Li Shaoshuo , Wang Jianwei , Peng Hongcheng , Rong Yi , Yu Hao , Liu Mingming 
Published: February 2023

Abstract
Background
Osteoporotic fracture (OPF) is one of the most common skeletal diseases in an aging society. The Chinese medicine formula Buzhong Yiqi Decoction (BZYQD) is commonly used for treating OPF. However, the essential bioactive compounds and the underlying molecular mechanisms that promote fracture repair remain unclear.

Methods
We used network pharmacology and experimental animal validation to address this issue. First, 147 bioactive BZYQD compounds and 32 target genes for treating OPF were screened and assessed. A BZYQD-bioactive compound-target gene-disease network was constructed using the Cytoscape software. Functional enrichment showed that the candidate target genes were enriched in oxidative stress- and inflammation-related biological processes and multiple pathways, including nuclear factor kappa B (NF-κB), and mitogen-activated protein kinase (MAPK) signaling pathways. Furthermore, an OPF rat model was established and treated with BZYQD.

Results
The results revealed that BZYQD ameliorated OPF characteristics, including femoral microarchitecture, biomechanical properties, and histopathological changes, in a dose-dependent manner. Results of enzyme-linked immunosorbent assay showed that BZYQD reduced the serum’s pro-inflammatory cytokines [Tumor necrosis factor-alpha (TNF-α), Interleukin (IL)-1β, and IL-6] and improved oxidative stress-related factors [glutathione (GSH) and superoxide dismutase (SOD)]. BZYQD significantly decreased the protein expression of NF-κB in OPF rat femurs, suppressed NF-κB activation, and activated the nuclear factor-erythroid factor 2-related factor (Nrf2)/heme oxygenase 1 (HO-1) and p38 MAPK as well ERK pathways.

Conclusions
Our results suggest that BZYQD could improve inflammation and oxidative stress during fracture repair by suppressing NF-κB and activating Nrf2/MAPK signaling pathways.
Vacuum-assisted closure versus conventional dressing in necrotizing fasciitis: a systematic review and meta-analysis
Authors: Zhang Rongli , Zhang Yahui , Hou Liyuan , Yan Chengyong 
Published: February 2023

Abstract
Background
Necrotizing fasciitis is a rapid and severe soft tissue infection that targets subcutaneous fat tissue, muscle, and fascia. This study compares the clinical outcomes of vacuum-assisted closure (VAC) versus conventional dressing on necrotizing fasciitis.

Methods
We systematically searched Embase, Cochrane, and PubMed for clinical trials (published between January 1, 1995 and September 30, 2021), which compared VAC with conventional dressing for necrotizing fasciitis. The mortality rate of necrotizing fasciitis was the primary outcome of this study. The number of debridements, the total length of hospital stay, and the complication rate were secondary outcomes. A random effects model assessed all pooled data.

Results
A total of 230 identified studies and seven controlled clinical trials met the inclusion criteria and were included in this analysis (n = 249 participants). Compared to the conventional dressing, patients treated with VAC had a significantly lower mortality rate [OR = 0.27, 95% CI (0.09, 0.87)] (P = 0.03). Total length of hospital stays [MD = 8.46, 95% CI (− 0.53, 17.45)] (P = 0.07), number of debridements [MD = 0.86, 95% CI (− 0.58, 2.30)] (P = 0.24), and complication rate [OR = 0.64, 95% CI (0.07, 5.94)] (P = 0.69) were not significant. These results did not show significant differences between both groups treated with VAC or conventional treatment.

Conclusion
VAC could significantly decrease the death rate compared to conventional dressing. No significant impacts were found on the number of debridements, the total length of hospital stay, and the complication rate in this study.
Level of evidence Level-III.
Registration Research Registry (reviewregistry1246).
Effects of a locally administered risedronate/autogenous bone graft combination on bone healing in a critical-size rabbit defect model
Authors: Özer Taha , Guliyeva Vusala , Aktaş Alper , Barış Emre , Ocak Mert 
Published: February 2023

Abstract
Background
Risedronate is a bisphosphonate with poor oral absorption. An extremely hydrophilic molecule that has a high affinity for bone, risedronate also inhibits the farnesyl diphosphate synthase enzyme, inhibiting osteoclastic activity and reducing bone turnover and resorption. Autogenous bone grafts contain osteogenic cells and osteoinductive factors that are essential for bone regeneration and are therefore considered the gold standard. Thus, this study aimed to investigate the impact of local risedronate administered with autogenous bone grafts on the healing of defects in rabbit skulls using histological, histomorphometric, immunohistochemical, and three-dimensional radiological methods.

Methods
Two 10-mm-diameter critical-size defects were created in 16 rabbits and filled with autogenous bone graft and autogenous bone graft + 5 mg risedronate in the control (C) and risedronate (RIS) groups, respectively. Residual graft, new bone, soft tissue areas, and bone volume were evaluated in the 4- and 8-week study groups.

Results
There were no statistically significant differences in bone graft, new bone, or soft tissue area between the groups at 4 weeks (p > 0.05). At 8 weeks, the new bone area was significantly higher in the RIS group than in the C group (p < 0.05). The h scores obtained from sialoprotein and osteopontin did not differ significantly between the groups (p > 0.05). The radiologically measured total bone volume was significantly higher in the RIS group than in the C group at both time points (p < 0.05).

Conclusions
In this study, risedronate enhanced the osteoconductive properties of autogenous bone grafts and rapidly created better-quality bone. This could improve future patient outcomes.