Miracle-dz/UniFAR-FTUs huggingface dataset:
Fluvastatin alleviates doxorubicin-induced cardiac and renal toxicity in rats via regulation of oxidative stress, inflammation, and apoptosis associated genes expressions

Abstract Doxorubicin (DOXO) is a cytostatic agent used in the chemotherapy protocol of several cancers for more than 40 years, but usage of this drug in cancer treatment has been limited due to severe renal and cardiac tissue toxicities that may result in death in patients. Fluvastatin (FV) is a fully synthetic hydroxymethyl glutaryl coenzyme A (HMG-CoA) reductase inhibitor used as a cholesterol-lowering agent in patients with hypercholesterolemia. Previous studies revealed that FV also exhibits antioxidant, anti-inflammatory, and antitumor activity. Additionally, our previous study indicated that FV exerts a prophylactic effect on DOXO-induced testicular toxicity by preventing lipid peroxidation, supporting the antioxidant system, and regulating the blood-testis barrier-associated genes expression. Herein, we purposed to evaluate the possible therapeutic and the protective effects of FV on the DOXO-induced cardiac and renal toxicitiy model by histochemical, immunohistochemical, biochemical, and real-time polymerase chain reaction (real-time PCR) analyses. Results point out protective use of FV exerts a beneficial effect by repressing lipid peroxidation and by regulating the inducible nitric oxide synthase (iNOS), nitric oxide synthase endothelial (eNOS), nuclear factor kappa-B (NF-κB), and Caspase-3 (Casp3) protein and mRNA expressions, which play an important role in mediating DOXO-induced renal and cardiac toxicity mechanisms. In conclusion, FV may be a candidate agent for the prevention of renal and cardiac toxicities in cancer patients receiving DOXO chemotherapy.
Delays in Time to Head and Neck Cancer Treatment: A South Australian Perspective

Background and Objectives: In head and neck cancer, delays in time to treatment are associated with poorer clinical outcomes. Within Australia, it is recommended that primary treatment is initiated within 56 days of initial referral. The aim of this study was to assess whether head and neck cancer treatment was delivered within these timeframe guidelines at our institution and identify factors associated with treatment delays. Methods: This retrospective cohort study assessed patients newly diagnosed with head and neck cancer over a 24 months period (2018 to 2019) at Flinders Medical Centre, Australia. Time to treatment intervals were calculated for comparison to local timeframe guidelines. Results: A total of 72 patients met the inclusion criteria. The median time from specialist referral to treatment initiation was 45.5 days (IQR 29–61), with 72% meeting the 56 days guideline. On univariate logistic regression, patients undergoing primary radiotherapy treatment were less likely to meet this guideline than those undergoing primary surgery (OR 8.8, 95% CI 2.6–28.9, p < 0.001), as were those requiring prophylactic gastrostomy tube insertion (OR 3.1, 95% CI 1.1–9.0, p < 0.05). Treatment initiation beyond 56 days had no significant impact on 12 months overall survival or disease-free survival. Conclusions: The findings of this study demonstrate that primary radiotherapy treatment is associated with delays in head and neck cancer treatment initiation, likely related to time consuming pre-treatment factors such as gastrostomy tube insertion.
Advancements in Fabrication and Application of Chitosan Composites in Implants and Dentistry: A Review

Chitosan is a biopolymer that is found in nature and is produced from chitin deacetylation. Chitosan has been studied thoroughly for multiple applications with an interdisciplinary approach. Antifungal antibacterial activities, mucoadhesion, non-toxicity, biodegradability, and biocompatibility are some of the unique characteristics of chitosan-based biomaterials. Moreover, chitosan is the only widely-used natural polysaccharide, and it is possible to chemically modify it for different applications and functions. In various fields, chitosan composite and compound manufacturing has acquired much interest in developing several promising products. Chitosan and its derivatives have gained attention universally in biomedical and pharmaceutical industries as a result of their desired characteristics. In the present mini-review, novel methods for preparing chitosan-containing materials for dental and implant engineering applications along with challenges and future perspectives are discussed.
The evidence to date on umbralisib for the treatment of refractory marginal zone lymphoma and follicular lymphoma

ABSTRACT Introduction Between 2014 and 2018 The United States Food and Drug Administration granted approvals for three small molecule inhibitors of phosphoinositide 3-kinases (PI3Ks) as monotherapy for follicular lymphoma relapsed after at least 2 prior therapies. Idelalisib, copanlisib, and duvelisib each showed similar overall response rate and progression-free survival efficacy along with significant toxicity in separate phase II single-arm studies. Umbralisib, as the 4th iteration in this PI3K-inhibitor class for relapsed/refractory indolent B-cell lymphoma (iB-NHL), appears comparably active but may have improved tolerability. Areas Covered We review the use and limitations of PI3K-inhibitors for iB-NHL and discuss the development of and clinical results for umbralisib. Efficacy data are contextualized alongside other PI3K-inihibitors within the limitations of published single-arm studies. We compare and contrast available safety data, covering the off-target inhibition by umbralisib of casein kinase 1ε that is thought to contribute to a more favorable immune-mediated toxicity profile. Expert Opinion Though a late-comer to the PI3K-inihibitor party in iB-NHL, umbralisib may carve out an important role in treatment algorithms. Umbralisib's apparently superior safety needs to be confirmed in real-world and, ideally, comparative studies but stands to make it an attractive option in patients who are frail and/or seek treatments more compatible with remote management.
Clinical Decision Support with or without Shared Decision Making to Improve Preventive Cancer Care: A Cluster-Randomized Trial

Background Innovative interventions are needed to address gaps in preventive cancer care, especially in rural areas. This study evaluated the impact of clinical decision support (CDS) with and without shared decision making (SDM) on cancer-screening completion. Methods In this 3-arm, parallel-group, cluster-randomized trial conducted at a predominantly rural medical group, 34 primary care clinics were randomized to clinical decision support (CDS), CDS plus shared decision making (CDS+SDM), or usual care (UC). The CDS applied web-based clinical algorithms identifying patients overdue for United States Preventive Services Task Force–recommended preventive cancer care and presented evidence-based recommendations to patients and providers on printouts and on the electronic health record interface. Patients in the CDS+SDM clinic also received shared decision-making tools (SDMTs). The primary outcome was a composite indicator of the proportion of patients overdue for breast, cervical, or colorectal cancer screening at index who were up to date on these 1 y later. Results From August 1, 2018, to March 15, 2019, 69,405 patients aged 21 to 74 y had visits at study clinics and 25,198 were overdue for 1 or more cancer screening tests at an index visit. At 12-mo follow-up, 9,543 of these (37.9%) were up to date on the composite endpoint. The adjusted, model-derived percentage of patients up to date was 36.5% (95% confidence interval [CI]: 34.0–39.1) in the UC group, 38.1% (95% CI: 35.5–40.9) in the CDS group, and 34.4% (95% CI: 31.8–37.2) in the CDS+SDM group. For all comparisons, the screening rates were higher than UC in the CDS group and lower than UC in the CDS+SDM group, although these differences did not reach statistical significance. Conclusion The CDS did not significantly increase cancer-screening rates. Exploratory analyses suggest a deeper understanding of how SDM and CDS interact to affect cancer prevention decisions is needed. Trial registration: ClinicalTrials.gov ID: NCT02986230, December 6, 2016.
PTEN Loss and BRCA1 Promoter Hypermethylation Negatively Predict for Immunogenicity in BRCA-Deficient Ovarian Cancer

PURPOSE Ovarian cancers can exhibit a prominent immune infiltrate, but clinical trials have not demonstrated substantive response rates to immune checkpoint blockade monotherapy. We aimed to understand genomic features associated with immunogenicity in BRCA1/2 mutation–associated cancers. MATERIALS AND METHODS Using the Cancer Genome Atlas whole-exome sequencing, methylation, and expression data, we analyzed 66 ovarian cancers with either germline or somatic loss of BRCA1/2 and whole-exome sequencing, immunohistochemistry, and CyTOF in 20 ovarian cancers with germline BRCA1/2 pathogenic variants from Penn. RESULTS We found two groups of BRCA1/2 ovarian cancers differing in their immunogenicity: (1) 37 tumors significantly enriched for PTEN loss (11, 30%) and BRCA1 promoter–hypermethylated (10, 27%; P = .0016) and (2) PTEN wild-type (28 of 29 tumors) cancers, with the latter group having longer overall survival (OS; P = .0186, median OS not reached v median OS = 66.1 months). BRCA1/2-mutant PTEN loss and BRCA1 promoter–hypermethylated cancers were characterized by the decreased composition of lymphocytes estimated by gene expression (P = .0030), cytolytic index (P = .034), and cytokine expression but higher homologous recombination deficiency scores (P = .00013). Large-scale state transitions were the primary discriminating feature (P = .001); neither mutational burden nor neoantigen burden could explain differences in immunogenicity. In Penn tumors, PTEN loss and high homologous recombination deficiency cancers exhibited fewer CD3+ (P = .05), CD8+ (P = .012), and FOXP3+ (P = .0087) T cells; decreased PRF1 expression (P = .041); and lower immune costimulatory and inhibitory molecule expression. CONCLUSION Our study suggests that within ovarian cancers with genetic loss of BRCA1/2 are two subsets exhibiting differential immunogenicity, with lower levels associated with PTEN loss and BRCA hypermethylation. These genomic features of BRCA1/2-associated ovarian cancers may inform considerations around how to optimally deploy immune checkpoint inhibitors in the clinic. Immune environment is associated with specific genomic features in BRCA-deficient ovarian cancer.
Astrocytic modulation of central pattern generating motor circuits

Central pattern generators (CPGs) generate the rhythmic and coordinated neural features necessary for the proper conduction of complex behaviors. In particular, CPGs are crucial for complex motor behaviors such as locomotion, mastication, respiration, and vocal production. While the importance of these networks in modulating behavior is evident, the mechanisms driving these CPGs are still not fully understood. On the other hand, accumulating evidence suggests that astrocytes have a significant role in regulating the function of some of these CPGs. Here, we review the location, function, and role of astrocytes in locomotion, respiration, and mastication CPGs and propose that, similarly, astrocytes may also play a significant role in the vocalization CPG.
Developing CMOS compatible Electro Wetting-on-Dielectric (EWOD) microfluidic technology

The work presented in this thesis is associated with the development of electrowetting on dielectric (EWOD) technology. One of the main issues of concern was robustly driving droplet movement using low voltage without device malfunction caused by poor dielectric quality. In this work, anodic Ta205 dielectric, an alternative insulator with a high i' (8 to 25) was used to fabricate low voltage EWOD systems. The uniform and pinhole-free layer has a surface roughness of a few angstroms, enabling an ultra thin Amorphous Fluoropolymer (aFP) layer to be employed to reduce the EWOD driving voltage to 13V. The result shows that, when the i reaches a certain level, a smooth insulating surface and a thin layer of aEP is more important than a higher value of the dielectric constant in achieving low voltage EWOD droplet maniulation. Further achievements of this work is the integration of an active EWOD device with CMOS technology. One of the motivations behind this approach is based upon the desire to increase the number of control electrodes, requiring the implementation of on-chip microelectronic linecolumn drivers. Increasing the number of electrodes is attractive as it provides the opportunity to finely adjust droplet size, and also increases the number of droplets that can be moved simultaneously. Moreover, the integration can provide on chip sensing, which is disirable in Lab-on-a-chip applications. The tradeoffs associated with minimising the drive voltage while keeping the postprocess simple and low cost are assessed. Taking issues into account, the first active EWOD device was successfully fabricated and used to demonstrate droplet manipulation. This thesis also reports two applications related to lab-on-a-chip and microrobotics developed using the above technologies. The capability to expand the system by using low voltage and active EWOD technology is highlighted in discussing future work.
Simulating Ideal Assistive Strategies to Reduce the Metabolic Cost of Walking in the Elderly

Objective: Development of walking assist exoskeletons is a growing area of study, offering a solution to restore, maintain, and enhance mobility. However, applying this technology to the elderly is challenging and there is currently no consensus as to the optimal strategy for assisting elderly gait. The gait patterns of elderly individuals often differ from those of the younger population, primarily in the ankle and hip joints. This study used musculoskeletal simulations to predict how ankle and hip actuators might affect the energy expended by elderly participants during gait. Methods: OpenSim was used to generate simulations of 10 elderly participants walking at self-selected slow, comfortable, and fast speeds. Ideal flexion/extension assistive actuators were added bilaterally to the ankle or hip joints of the models to predict the maximum metabolic power that could be saved by exoskeletons that apply torques at these joints. Results: Compared to the unassisted scenario, the use of ideal hip actuators resulted in 21±5%, 26±5%, and 30±6% reductions in average metabolic power consumption at slow, comfortable, and fast walking speeds, respectively; use of ideal ankle actuators resulted in 12±3%, 14±2%, and 16±1% metabolic savings, respectively. Conclusion: The simulations suggest that providing hip assistance to elderly individuals during walking can result in significantly greater metabolic savings than ankle assistance, assuming kinematics and total joint moments do not change substantially with assistance. Significance: The achieved research results and analysis provide exoskeleton developers guidance on optimally designing walking assist exoskeletons, thus promoting consensus toward the optimal strategy for assisting elderly individuals.
Self‐Assembled Human Skin Equivalents Model Macrophage Activation of Cutaneous Fibrogenesis in Systemic Sclerosis

The development of precision therapeutics for systemic sclerosis (SSc) has been hindered by the lack of models that accurately mimic the disease in vitro. This study was undertaken to design and test a self‐assembled skin equivalent (saSE) system that recapitulates the cross‐talk between macrophages and fibroblasts in cutaneous fibrosis.
Toward Compilation of Balanced Protein Stability Data Sets: Flattening the ΔΔG Curve through Systematic Enrichment

Often studies analyzing stability data sets and/or predictors ignore neutral mutations and use a binary classification scheme labeling only destabilizing and stabilizing mutations. Recognizing that highly concentrated neutral mutations interfere with data set quality, we have explored three protein stability data sets: S2648, PON-tstab, and the symmetric Ssym that differ in size and quality. A characteristic leptokurtic shape in the ΔΔG distributions of all three data sets including the curated and symmetric ones was reported due to concentrated neutral mutations. To further investigate the impact of neutral mutations on ΔΔG predictions, we have comprehensively assessed the performance of 11 predictors on the PON-tstab data set. Correlation and error analyses showed that all of the predictors performed the best on the neutral mutations, while their performance became gradually worse as the ΔΔG of the mutations departed further from the neutral zone regardless of the direction, implying a bias toward dense mutations. To this end, after unraveling the role of concentrated neutral mutations in biases of stability data sets, we described a systematic enrichment approach to balance the ΔΔG distributions. Before enrichment, mutations were clustered based on their biochemical and/or structural features, and then three mutations were selected from every 2 kcal/mol of each cluster. Upon implementation of this approach by distinct clustering schemes, we generated five subsets varying in size and ΔΔG distributions. All subsets showed improved ΔΔG and frequency distributions. We ultimately reported that the errors toward enriched subsets were higher than those toward the parent data sets, confirming the enrichment of difficult-to-predict mutations in the subsets. In summary, we elaborated the prediction bias toward a concentrated neutral zone and also implemented a rational strategy to tackle this and other forms of biases. Ultimately, this study equipping us with an extended view of shortcomings of stability data sets is a step taken toward development of an unbiased predictor.
Hybrid motion artifact detection and correction approach for functional near-infrared spectroscopy measurements

Abstract. Significance: Functional near-infrared spectroscopy (fNIRS) is a promising optical neuroimaging technique, measuring the hemodynamic signals from the cortex. However, improving signal quality and reducing artifacts arising from oscillation and baseline shift (BS) are still challenging up to now for fNIRS applications. Aim: Considering the advantages and weaknesses of the different algorithms to reduce the artifact effect in fNIRS signals, we propose a hybrid artifact detection and correction approach. Approach: First, distinct artifact detection was realized through an fNIRS detection strategy. Then the artifacts were divided into three categories: BS, slight oscillation, and severe oscillation. A comprehensive correction was applied through three main steps: severe artifact correction by cubic spline interpolation, BS removal by spline interpolation, and slight oscillation reduction by dual-threshold wavelet-based method. Results: Using fNIRS data acquired during whole night sleep monitoring, we compared the performance of our approach with existing algorithms in signal-to-noise ratio (SNR) and Pearson’s correlation coefficient (R). We found that the proposed method showed improvements in performance in SNR and R with strong stability. Conclusions: These results suggest that the new hybrid artifact detection and correction method enhances the viability of fNIRS as a functional neuroimaging modality.
Facilitators and barriers of mental health help-seeking behaviours among adolescents in Oman: a cross-sectional study

Abstract Objectives This study aimed to explore and identify facilitators and barriers to help-seeking behaviours among adolescents in Oman, by exploring the relationship between knowledge, attitude, and behaviour towards mental health help-seeking. Methods A cross-sectional descriptive study was used and 424 adolescents were recruited to participate in the study. Participants were asked to complete five self-reported questionnaires, including two open-ended questions about the main motivations and barriers to seeking professional help for mental problems. Results It was found that those with positive help-seeking attitudes towards mental health were more knowledgeable about mental health, had more positive attitudes towards mental illness, and had higher intention to help seeking. On the contrary, those with higher help-seeker stereotypes had more negative attitudes towards mental illness. Having an adequate support system, being positive and knowledgeable about mental illness, and the reputation of mental health are the main factors facilitating seeking professional help. However, fear, lack of family support, and the time-consuming procedures were the main barriers emerging from the open-ended questions. Conclusions This study contributes by identifying facilitating factors as well as barriers in an Arabic context (Oman) to fill the exiting knowledge gap; both need to be considered when planning interventions targeting the younger individuals in this society.
Establishing an air-liquid interface exposure system for exposure of lung cells to gases

Abstract Objective Growing interest in non-animal-based models has led to the development of devices to expose cells to airborne substances. Cells/tissues grown at the air-liquid interface (ALI) are more representative of lung cells/tissues in vivo compared to submerged cell cultures. Additionally, airborne exposures should allow for closer modeling of human lung toxicity. However, such exposures present technical challenges, including maintaining optimal cell health, and establishing consistent exposure monitoring and control. We aimed to establish a reliable system and procedures for cell exposures to gases at the ALI. Methods We tested and adapted a horizontal-flow ALI-exposure system to verify and optimize temperature, humidity/condensation, and control of atmosphere delivery. We measured temperature and relative humidity (RH) throughout the system, including at the outlet (surrogate measures) and at the well, and evaluated viability of lung epithelial A549 cells under control conditions. Exposure stability, dosimetry, and toxicity were tested using ozone. Results Temperatures measured directly above wells vs. outflow differed; using above-well temperature enabled determination of near-well RH. Under optimized conditions, the viability of A549 cells exposed to clean air (2 h) in the ALI system was unchanged from incubator-grown cells. In-well ozone levels, determined through reaction with potassium indigotrisulfonate, confirmed dosing. Cells exposed to 200 ppb ozone at the ALI presented reduced viability, while submerged cells did not. Conclusion Our results emphasize the importance of monitoring near-well conditions rather than relying on surrogate measures. Rigorous assessment of ALI exposure conditions led to procedures for reproducible exposure of cells to gases.