bluuebunny/crossref_metadata_2025_split huggingface dataset:
NIR-Triggered and ROS-Boosted Nanoplatform for Enhanced Chemo/PDT/PTT Synergistic Therapy of Sorafenib in Hepatocellular Carcinoma
Authors: Wang Chonggao , Cheng Xiaolan , Peng Hao , Zhang Yewei 
Published: September 2022

AbstractAlthough being the first-line treatment of advanced hepatocellular carcinoma (HCC), sorafenib (SOR) outcome is limited due to drug resistance and low tumor accumulation. Herein, with MnO2 as photothermal agent and chlorine6 (Ce6) as photosensitizer, a tumor-targeting and NIR-triggered multifunctional nanoplatform loading sorafenib (MnO2-SOR-Ce6@PDA-PEG-FA, MSCPF) was constructed. Owing to oxygen generator MnO2, MSCPF could generate excessive ROS, thus can alleviate tumor hypoxia and improve sorafenib accumulation in cancer cells. Besides, ROS production further strengthens Ce6-mediated PDT and PDA-mediated PTT. By exploiting these features, MSCPF exhibited excellent antitumor effects on HCC in the in vitro and in vivo studies, compared to solo sorafenib or PDT/PTT treatment. Further mechanism experiments suggested that MSCPF could inhibit P-gp expression and induce ferroptosis via deactivation of GPX4 and SLC7A11, which ultimately enhanced the antitumor efficacy of SOR. In summary, our work highlights a promising NIR-triggered and ROS-boosted nanoplatform for enhanced chemo/PDT/PTT synergistic therapy of SOR in HCC treatment.
MiR-99a alleviates apoptosis and extracellular matrix degradation in experimentally induced spine osteoarthritis by targeting FZD8
Authors: Wang Yeyang , Zheng Xiaoyu , Luo Dixin , Xu Wangyang , Zhou Xiaozhong 
Published: September 2022

Abstract
Background
Our previous study identified miR-99a as a negative regulator of early chondrogenic differentiation. However, the functional role of miR-99a in the pathogenesis of osteoarthritis (OA) remains unclear.

Methods
We examined the levels of miR-99a and Frizzled 8 (FZD8) expression in tissue specimens. Human SW1353 chondrosarcoma cells were stimulated with IL-6 and TNF-α to construct an in vitro OA environment. A luciferase reporter assay was performed to analyze the relationship between miR-99a and FZD8. CCK-8 assays, flow cytometry, and ELISA assays were used to assess cell viability, apoptosis, and inflammatory molecule expression, respectively. Percutaneous intra-spinal injections of papain mixed solution were performed to create an OA Sprague–Dawley rat model. Alcian Blue staining, Safranin O Fast Green staining, and Toluidine Blue O staining were performed to detect the degrees of cartilage injury.

Results
MiR-99a expression was downregulated in the severe spine OA patients when compared with the mild spine OA patients, and was also decreased in the experimentally induced in vitro OA environment when compared with the control environment. Functionally, overexpression of miR-99a significantly suppressed cell apoptosis and extracellular matrix degradation stimulated by IL-6 and TNF-α. FZD8 was identified as a target gene of miR-99a. Furthermore, the suppressive effects of miR-99a on cell injury induced by IL-6 and TNF-α were reversed by FZD8 overexpression. Moreover, the levels of miR-99a expression were also reduced in the induced OA model rats, and miR-99a agomir injection relieved the cartilage damage. At the molecular level, miR-99a overexpression downregulated the levels of MMP13, β-catenin, Bax, and caspase-3 protein expression and upregulated the levels of COL2A1 and Bcl-2 protein expression in the in vitro OA-like chondrocyte model and also in the experimental OA model rats.

Conclusions
Our data showed that miR-99a alleviated apoptosis and extracellular matrix degradation by targeting FZD8, and thereby suppressed the development and progression of experimentally induced spine osteoarthritis.
Effects of stabilized hypochlorous acid on oral biofilm bacteria
Authors: Aherne Olivia , Ortiz Roberto , Fazli Magnus M. , Davies Julia R. 
Published: September 2022

Abstract
Background
Caries and periodontitis are amongst the most prevalent diseases worldwide, leading to pain and loss of oral function for those affected. Prevention relies heavily on mechanical removal of dental plaque biofilms but for populations where this is not achievable, alternative plaque control methods are required. With concerns over undesirable side-effects and potential bacterial resistance due to the use of chlorhexidine gluconate (CHX), new antimicrobial substances for oral use are greatly needed. Here we have investigated the antimicrobial effect of hypochlorous acid (HOCl), stabilized with acetic acid (HAc), on oral biofilms and compared it to that of CHX. Possible adverse effects of stabilized HOCl on hydroxyapatite surfaces were also examined.

Methods
Single- and mixed-species biofilms of six common oral bacteria (Streptococcus mutans, Streptococcus gordonii, Actinomyces odontolyticus, Veillonella parvula, Parvimonas micra and Porphyromonas gingivalis) within a flow-cell model were exposed to HOCl stabilized with 0.14% or 2% HAc, pH 4.6, as well as HOCl or HAc alone. Biofilm viability was assessed in situ using confocal laser scanning microscopy following LIVE/DEAD® BacLight™ staining. In-situ quartz crystal microbalance with dissipation (QCM-D) was used to study erosion of hydroxyapatite (HA) surfaces by stabilized HOCl.

Results
Low concentrations of HOCl (5 ppm), stabilized with 0.14% or 2% HAc, significantly reduced viability in multi-species biofilms representing supra- and sub-gingival oral communities, after 5 min, without causing erosion of HA surfaces. No equivalent antimicrobial effect was seen for CHX. Gram-positive and Gram-negative bacteria showed no significant differential suceptibility to stabilized HOCl.

Conclusions
At low concentrations and with exposure times which could be achieved through oral rinsing, HOCl stabilized with HAc had a robust antimicrobial activity on oral biofilms, without causing erosion of HA surfaces or affecting viability of oral keratinocytes. This substance thus appears to offer potential for prevention and/or treatment of oral biofilm-mediated diseases.
Disability-friendly healthcare at public health facilities in Bangladesh: a mixed-method study to explore the existing situation
Authors: Torsha Nawshin , Rahman Farah Naz , Hossain Md Shafkat , Chowdhury Hasina Akhter , Kim Minjoon , Rahman S. M. Mustafizur , Rahman A. K. M. Fazlur , Rahman Aminur 
Published: September 2022

Abstract
Background

Several strategies and policies are being implemented in Bangladesh to address the healthcare needs of people with disabilities, who comprise about 10% of the country’s total population. However, these measures are not adequate to provide accessible or friendly healthcare to the people with disabilities. This study aimed to explore the disability-friendliness of healthcare facilities, and the challenges of people with disabilities in terms of access to 1) information and communication, 2) access to infrastructure, and 3) providers’ capacity in Bangladesh.

Methods
An explanatory sequential mixed-method study was conducted, including a cross-sectional survey of healthcare facilities, followed by structured-interview with people with disabilities and healthcare managers, and qualitative interviews among people with disabilities or their caregivers, healthcare providers (HCPs), policymakers, and community leaders. Data were collected from 150 public healthcare (primary-to-tertiary) facilities and from 300 people with disabilities in 16 districts across Bangladesh between January-December 2019. An observational checklist and structured questionnaires were used to assess the situation of healthcare facilities, and literature-guided guidelines were used for qualitative interviews. During analysis, the disability-friendliness of healthcare facilities were quantified through a scoring system, and thematic analysis of qualitative data was performed to identify the challenges of implementing disability-friendly healthcare (DFHC).

Results
The score for providing DFHC was low across all the four objectives in the healthcare facilities. The highest score (mean percentage) was observed in the infrastructure domain: 29.3 ± 20.5, followed by communication: 18.2 ± 4.8, and information: 14.6 ± 6.22, and the lowest (0.93 ± 7.1) score was for capacity of the HCPs to provide DFHC. Mean percentage scores for access to 13 infrastructure points were low, and extremely low scores were found in areas such as access to elevators (5.6 ± 5.0), ticket counters (7.3 ± 17.7) and toilets (10.6 ± 9.3). Furthermore, about 59.1% of people with disabilities expressed dissatisfaction regarding access to information and communication. The majority (98.2%) recommended that training of HCPs can improve the situation.

Conclusion
This study revealed that most of the public health facilities in Bangladesh were not disability-friendly. Findings can inform development of a national disability-friendly policy with implementation guidelines.
The noncoding RNAs regulating pyroptosis in colon adenocarcinoma were derived from the construction of a ceRNA network and used to develop a prognostic model
Authors: Chen Yanfeng , Tian Zongbiao , Hou Hebin , Gai Wei 
Published: September 2022

AbstractBackgroundNoncoding RNAs (ncRNAs), pyroptosis and tumours are all hot topics in current research, but there are very limited studies on pyroptosis and its regulated ncRNAs in colon adenocarcinoma (COAD).MethodsThe COAD transcription profile dataset from TCGA was used for differential expression analysis. Pyroptosis-related genes (PRGs), the top 200 long noncoding RNAs (lncRNAs) and circular RNA (circRNAs) were selected from the results to construct an endogenous competitive RNA (ceRNA) network. Moreover, the expression of the ceRNAs was used for consensus cluster analysis of COAD and developing a risk model after combining clinical follow-up data by the least absolute shrinkage and selection operator method. The stability and independent prognostic ability of the risk model were evaluated. Finally, gene set enrichment analysis (GSEA) and immune score comparisons between the high-risk and low-risk groups were performed.ResultsThere were 87 PRGs with significant differences, among which casp3/8, NLRP1/3, and IL-1α/1β were at the core of the interactions. The ceRNA network consisted of 58 lncRNAs, 6 circRNAs, 25 PRGs, and 55 microRNAs. We speculated that KCNQ1OT1-miRNAs-SQSTM1 and HSA_CIRC_0001495-miRNAs-PTEN have great potential and value in the pyroptosis mechanism of COAD. Nine RNAs were involved in the risk score, which had excellent independent prognostic ability. Survival analyses were significant between the high-risk (HR) and low-risk (LR) groups (training cohort:P < 0.001; test cohort:P = 0.037). GSEA was mainly enriched in tumour proliferation and metastasis related pathways, while differences in immune activity showed a bipolar distribution between the HR and LR groups.ConclusionsThe overall mechanism of pyroptosis in COAD was revealed. CeRNAs most closely related to the pyroptosis mechanism of COAD were selected and used to develop a prognostic model. The results may present new regulatory sites and potential targets for COAD pyroptosis mechanisms.
Nut consumption is associated with a shift of the NMR lipoprotein subfraction profile to a less atherogenic pattern among older individuals at high CVD risk
Authors: García-Gavilán Jesús F. , Connelly Margery A. , Babio Nancy , Mantzoros Christos S. , Ros Emilio , Salas-Salvadó Jordi 
Published: September 2022

Abstract
Background
Scientific evidence has accumulated on the beneficial effects of nut consumption on cardiovascular risk and cholesterol reduction, but few studies have examined the effects of nuts on advanced measures of lipoprotein atherogenicity determined by nuclear magnetic resonance (NMR) spectroscopy. We analyzed associations between the amount and type of of nuts consumed and advanced measures of lipoprotein atherogenity and insulin resistance in older individuals at high cardiovascular risk.

Methods
The present observational study was carried out within the framework of the Prevención con Dieta Mediterránea (PREDIMED) trial. Cross-sectional and longitudinal analyses after 1-year of follow-up were conducted in 196 men and women recruited in the PREDIMED-Reus (Spain) center. Dietary intake was assessed using a validated semi-quantitative food questionnaire. Baseline and 1-year fasting plasma lipoprotein and metabolite profiling were performed in plasma using NMR spectra Vantera® Clinical Analyzer. Associations by tertiles of nut consumption between baseline and 1-year changes and advanced measures of lipoprotein atherogenicity, branched chain amminoacids, and measures of insulin resistance were tested by multivariable-adjusted ANCOVA models.

Results
Compared to paticipants in the bottom tertile, those in the top tertile of total nut consumption showed higher levels of large HDL particles and HDL-cholesterol, lower levels of branched-chain amino acids (BCAA) and GlycA, and reduced lipoprotein insulin resistance and diabetes risk index. Participants in the top tertile of walnut consumption disclosed lower levels of very large VLDL, total LDL particles, LDL-cholesterol, and GlycA. Participants in the top tertile of non-walnut nut consumption displayed higher levels of total HDL particles, HDL-cholesterol and apoliporotein A1, lower BCAA and GlycA, and reduced lipoprotein insulin resistance. Participants in the top tertile of 1-year changes in walnut consumption showed increases in medium-sized HDL particles in comparison to the bottom tertile.

Conclusions
In older individuals at high cardiovascular risk, increasing nut consumption was associated with a shift of the NMR lipoprotein subfraction profile to a less atherogenic pattern, as well as lower circulating concentrations of BCAA and decreased insulin resistance. These results provide novel mechanistic insight into the cardiovascular benefit of nut consumption.
Trial registration ISRCTN35739639; registration date: 05/10/2005; recruitment start date 01/10/2003.
Examining the impact of a symptom assessment application on patient-physician interaction among self-referred walk-in patients in the emergency department (AKUSYM): study protocol for a multi-center, randomized controlled, parallel-group superiority trial
Authors: Napierala Hendrik , Kopka Marvin , Altendorf Maria B. , Bolanaki Myrto , Schmidt Konrad , Piper Sophie K. , Heintze Christoph , Möckel Martin , Balzer Felix , Slagman Anna , Schmieding Malte L. 
Published: September 2022

Abstract
Background
Due to the increasing use of online health information, symptom checkers have been developed to provide an individualized assessment of health complaints and provide potential diagnoses and an urgency estimation. It is assumed that they support patient empowerment and have a positive impact on patient-physician interaction and satisfaction with care. Particularly in the emergency department (ED), symptom checkers could be integrated to bridge waiting times in the ED, and patients as well as physicians could take advantage of potential positive effects. Our study therefore aims to assess the impact of symptom assessment application (SAA) usage compared to no SAA usage on the patient-physician interaction in self-referred walk-in patients in the ED population.

Methods
In this multi-center, 1:1 randomized, controlled, parallel-group superiority trial, 440 self-referred adult walk-in patients with a non-urgent triage category will be recruited in three EDs in Berlin. Eligible participants in the intervention group will use a SAA directly after initial triage. The control group receives standard care without using a SAA. The primary endpoint is patients’ satisfaction with the patient-physician interaction assessed by the Patient Satisfaction Questionnaire.

Discussion
The results of this trial could influence the implementation of SAA into acute care to improve the satisfaction with the patient-physician interaction.

Trial registration
German Clinical Trials Registry DRKS00028598. Registered on 25.03.2022
Quality by design approach for development and validation of a RP-HPLC method for simultaneous estimation of xipamide and valsartan in human plasma
Authors: Sebaiy Mahmoud M. , El-Adl Sobhy M. , Baraka Mohamed M. , Hassan Amira A. , El-Sayed Heba M. 
Published: September 2022

AbstractA new rapid, simple, and sensitive RP-HPLC method was carried out through applying Quality by Design approach for determination of xipamide and valsartan in Human plasma. Fractional factorial design was used for screening of four independent factors: pH, flow rate, detection wavelength, and % of MeOH. Analysis of variance (ANOVA) confirmed that flow rate and % of MeOH were only significant. Chromatographic conditions optimization was carried out through using central composite design. Method analysis was performed using BDS Hypersil C8 column (250 × 4.6 mm, 5 μm) and an isocratic mobile phase of MeOH and 0.05 M KH2PO4buffer pH 3 (64.5:35.5, v/v) at 1.2 mL/min flow rate with UV detection at 240 nm and 10 μL injection volume. According to FDA guidelines, the method was then validated for the determination of the two drugs clinically in human plasma in respect of future pharmacokinetic and bioequivalence simulation studies. The standard curve was linear in the concentration range of 5–100 µg/mL for both drugs, with a determination coefficient (R2) of 0.999. Also, the average recoveries lied within the range from 99.89 to 100.03%. The proposed method showed good predictability and robustness.
Glycaemic control among type 2 diabetes patients in sub-Saharan Africa from 2012 to 2022: a systematic review and meta-analysis
Authors: Fina Lubaki Jean-Pierre , Omole Olufemi Babatunde , Francis Joel Msafiri 
Published: September 2022

AbstractBackgroundThere is an increased burden of diabetes globally including in sub-Saharan Africa. The literature shows that glycaemic control among type 2 diabetes patients is poor in most countries in sub-Saharan Africa. Understanding the factors influencing glycaemic control in this region is therefore important to develop interventions to optimize glycaemic control. We carried out a systematic review to determine the prevalence and factors associated with glycaemic control in sub-Saharan Africa to inform the development of a glycaemic control framework in the Democratic Republic of the Congo.MethodsWe searched five databases (African Index Medicus, Africa-Wide Information, Global Health, PubMed, and Web of Science) using the following search terms: type-2 diabetes, glycaemic control, and sub-Saharan Africa. Only peer-reviewed articles from January 2012 to May 2022 were eligible for this review. Two reviewers, independently, selected articles, assessed their methodological quality using Joanna Briggs checklists, and extracted data. A meta-analysis was performed to estimate the prevalence of glycaemic control. Factors associated with glycaemic control were presented as a narrative synthesis due to heterogeneity as assessed by the I2.ResultsA total of 74 studies, involving 21,133 participants were included in the review. The pooled prevalence of good glycaemic control was 30% (95% CI:27.6–32.9). The glycaemic control prevalence ranged from 10–60%. Younger and older age, gender, lower income, absence of health insurance, low level of education, place of residence, family history of diabetes, longer duration of diabetes, pill burden, treatment regimen, side effects, use of statins or antihypertensives, alcohol consumption, smoking, presence of comorbidities/complications, and poor management were associated with poor glycaemic control. On the other hand, positive perceived family support, adequate coping strategies, high diabetes health literacy, dietary adherence, exercise practice, attendance to follow-up, and medication adherence were associated with good glycaemic control.ConclusionSuboptimal glycaemic control is pervasive among patients with type-2 diabetes in sub-Saharan Africa and poses a significant public health challenge. While urgent interventions are required to optimize glycaemic control in this region, these should consider sociodemographic, lifestyle, clinical, and treatment-related factors. This systematic review and meta-analysis protocol is registered in PROSPERO under CRD 42021237941.
Impact of pain severity on functioning domains, sleep, and cognition in painful diabetic peripheral polyneuropathy patients
Authors: Abo-Elfetoh Noha M. , Farag Andrew I. , Gabra Romany H. 
Published: September 2022

Abstract
Background
Several studies have observed that painful diabetic peripheral polyneuropathy (PDPN) had an impact on the level of functioning domains and quality of sleep as well as cognitive functions. This study is aimed to explore the relationship between severity of pain and level of functioning, sleep quality, and cognitive functions among these patients. We recruited 100 diabetics with a mean HbA1C% of 7.3±0.9, diagnosed with PDPN, and included in the study with a mean age of 51±12.8 years and disease duration of 10.2±7.4 years. The following assessment was done for each patient; clinical and neurophysiology assessment, routine laboratory assessment, measuring pain severity, and average pain severity interference scores using pain visual analog scale (VAS) and brief pain inventory (BPI) short form, respectively, sleep quality assessment using Pittsburgh Sleep Quality Index (PSQI) and Montreal cognitive function assessment (MOCA) scales.

Results
Moderate to severe pain was recorded in 71% of patients according to the VAS pain score. The severe pain group recorded the significant highest average pain severity and interference scores in BPI and domains compared to other less pain groups with average pain intensity scores of 7.5±0.6 vs 5.3±0.8 in the moderate and 3.3±0.4 in mild pain groups. Poor sleep quality and pattern were observed in these patients with a mean PSQI score of 6.8±3.1, and the severe pain group had a significant highest score of 9.4±2.3 compared to other less group scores of 7±2.3 and 3.7±1.8. Their mean MOCA score was low 24.2±2.2. Out of them 48/100 patients had mild cognitive impairment and recorded high frequency in the severe pain group (28/32) followed by the moderate pain (15/39) group. There is a significant correlation between the score of VAS and PSQI as well as MOCA.

Conclusions
Painful DPN patients had a poor level of functioning and sleep quality as well as cognitive impairment based on pain intensity.

Trial registration
This study was registered on a clinical trial with registration number NCT03275233 on 7 September 2017.
Promoting validation and cross-phylogenetic integration in model organism research
Authors: Cheng Keith C. , Burdine Rebecca D. , Dickinson Mary E. , Ekker Stephen C. , Lin Alex Y. , Lloyd K. C. Kent , Lutz Cathleen M. , MacRae Calum A. , Morrison John H. , O'Connor David H. , Postlethwait John H. , Rogers Crystal D. , Sanchez Susan , Simpson Julie H. , Talbot William S. , Wallace Douglas C. , Weimer Jill M. , Bellen Hugo J. 
Published: September 2022

ABSTRACT
Model organism (MO) research provides a basic understanding of biology and disease due to the evolutionary conservation of the molecular and cellular language of life. MOs have been used to identify and understand the function of orthologous genes, proteins, cells and tissues involved in biological processes, to develop and evaluate techniques and methods, and to perform whole-organism-based chemical screens to test drug efficacy and toxicity. However, a growing richness of datasets and the rising power of computation raise an important question: How do we maximize the value of MOs? In-depth discussions in over 50 virtual presentations organized by the National Institutes of Health across more than 10 weeks yielded important suggestions for improving the rigor, validation, reproducibility and translatability of MO research. The effort clarified challenges and opportunities for developing and integrating tools and resources. Maintenance of critical existing infrastructure and the implementation of suggested improvements will play important roles in maintaining productivity and facilitating the validation of animal models of human biology and disease.