Miracle-dz/UniFAR-FTUs huggingface dataset:
Healthcare use and costs in early breast cancer: a patient-level data analysis according to stage and breast cancer subtype

Background The cost of breast cancer care rises with higher stage at diagnosis; however, there are no real-world data regarding the cost of care according to breast cancer subtypes. This study aimed to estimate direct medical costs for early breast cancer care in the first 3 years after diagnosis according to subtype and stage, using patient-level data. Methods Women with newly diagnosed stage I–III breast cancer, admitted in 2012 to a Portuguese cancer centre were prospectively followed within the NEON-BC cohort. The use of health resources was obtained from each patient’s clinical and administrative records and costs were computed. Tumours were classified into the classic subtypes (hormone receptor-positive (HR+)/HER2−; HER2-positive (HER2+); triple-negative breast cancer (TNBC)) and surrogate intrinsic subtypes (luminal A-like; luminal B-like; HER2 enriched; basal like). Results A total of 703 patients were included: 48.9% had stage I, 35.8% stage II and 15.2% stage III breast cancer; 76.4% had HR+/HER2−, 15.9% HER2+ and 7.7% TNBC. Median cost of care was €9215/patient in stage I, €13 019/patient in stage II and €15 011/patient in stage III and €10 540/patient in HR+/HER2−, €11 224/patient in TNBC and €41 513/patient in HER2+ breast cancer. Systemic therapy accounted for 69.2% of the cost of care among patients with HER2+, 12.0% among HR+/HER2− and 7.5% among TNBC patients. Similar differences were observed across surrogate intrinsic subtypes. Conclusions The cost of early breast cancer care was mainly driven by the tumour subtype and, to a lesser extent, by stage. The median cost of care was fourfold higher among patients with HER2+ tumours compared with those with HR+/HER2− and TNBC. These data provide information for the economic evaluation of innovative treatments for early breast cancer and highlight the weight that targeted systemic therapy might have in the overall cost of care among patients with early breast cancer.
Nanomechanics in Monitoring the Effectiveness of Drugs Targeting the Cancer Cell Cytoskeleton

Increasing attention is devoted to the use of nanomechanics as a marker of various pathologies. Atomic force microscopy (AFM) is one of the techniques that could be applied to quantify the nanomechanical properties of living cells with a high spatial resolution. Thus, AFM offers the possibility to trace changes in the reorganization of the cytoskeleton in living cells. Impairments in the structure, organization, and functioning of two main cytoskeletal components, namely, actin filaments and microtubules, cause severe effects, leading to cell death. That is why these cytoskeletal components are targets for antitumor therapy. This review intends to describe the gathered knowledge on the capability of AFM to trace the alterations in the nanomechanical properties of living cells induced by the action of antitumor drugs that could translate into their effectiveness.
Biomolecule from Trigonella stellata from Saudi Flora to Suppress Osteoporosis via Osteostromal Regulations

Trigonella stellata has used in folk medicine as palatable and nutraceutical herb. It also regulates hypocholesterolemia, hypoglycemia, and has showed anti-inflammatory activities as well as antioxidants efficacy. Osteoporosis is a one of bone metabolic disorders and is continuously increasing worldwide. In the present study, caffeic acid was isolated from Trigonella stellata and identified using 1 D- and 2 D-NMR spectroscopic data. Caffeic acid was investigated on osteoblast and osteoclast in vitro using mice bone marrow-derived mesenchymal cells. Caffeic acid played reciprocal proliferation between osteoblast and osteoclast cells and accelerated the bone mineralization. It was confirmed by cytotoxicity, alkaline phosphatase (ALP), alizarin red S (ARS), and Tartrate resistant acid phosphatase (TRAP) assay. Caffeic acid regulated the osteogenic marker and upregulated the osteopontin, osteocalcin, and bone morphogenic proteins (BMP). Quantitative real time PCR and Western blot were used to quantify the mRNA and protein markers. It also regulated the matrix metalloprotease-2 (MMP-2) and cathepsin-K proteolytic markers in osteoclast cells. In addition, caffeic acid inhibited bone resorption in osteoclast cells. On the other hand, it upregulate osteoblast differentiation through stimulation of extracellular calcium concentrations osteoblast differentiation, respectively. The results also were confirmed through in silico docking of caffeic acid against cathepsin-B and cathepsin-K markers. These findings revealed that caffeic acid has a potential role in bone-metabolic disorder through its multifaceted effects on osteoblast and osteoclast regulations and controls osteoporosis.
MANAGEMENT PARADIGM

Further, my understanding of the nitrogen cycle literature (see attached Adv in Agronomy review) leads me to recommend that the protocol should grant GHG credits for the reduced CO2 emissions associated with a reduction in synthetic fertilizer production. This is a vital point; it has both indirect and direct impacts on improving GHG management and profound implications for improving N management so as to reduce negative global impacts of reactive N and CO2 emissions.
An assessment of the treatment information contained within the websites of direct-to-consumer orthodontic aligner providers.

BACKGROUND The use of direct-to-consumer (DTC) orthodontic aligners is growing. The purpose of this study was to evaluate the quality of information contained within the websites of DTC orthodontic aligner providers. METHODS Websites that satisfied inclusion criteria were assessed for the presence of specific treatment-related features. Four validated quality of information instruments and readability tools were used to evaluate the content of the websites. Descriptive statistical analyses and intra-examiner reliability tests were performed. RESULTS Twenty-one websites were evaluated. Few websites referred to the need for pre-treatment dental health (38.1%) and indefinite post-treatment retention (23.8%). Most websites (95.2%) were categorised as either "poor" or "very poor" according to their DISCERN scores. DISCERN items regarding information bias and treatment risks scored particularly poorly. Cohen's kappa intra-examiner reliability testing for DISCERN scores was 0.81-0.89. Three websites honoured 2 out of the 4 Journal of the American Medical Association benchmarks and 18 honoured one benchmark only. The readability scores indicated 'difficult to read' content. CONCLUSIONS The quality of information contained within the websites of DTC orthodontic aligner providers is poor. Patient consent for DTC aligner treatment based solely on the information contained within the websites is likely to be invalid.
Trace metals in combustion systems

(Chapter Headings) Chapter 1 Trace Metals in Combustion Systems. Chapter 2 Trace Metals in the Biofuels. Chapter 3 Trace Metals in Fossil Fuels. Chapter 4 Trace Metals in Post-Consumer Wastes. Chapter 5 Conventional Power Boiler Technologies and the Fate of Trace Metals. Chapter 6 The Fate of Trace Metals in Fluidized Bed Combustion. Chapter 7 Trace Metals and Combustion in Rotary Kilns. Subject Index.
Barriers and facilitators to colorectal cancer screening among older Korean Americans: A focus group study

ABSTRACT A qualitative study was undertaken to explore the barriers and facilitators to colorectal cancer (CRC) screening among older Korean Americans (KAs). Four focus groups with 25 male and female KA participants and one focus group comprising five KA health professionals were conducted in the Atlanta Metropolitan area. Interpretive analyses of the interview data revealed barriers regarding CRC screening for KAs included a lack of CRC knowledge, embarrassment during the screening tests, CRC-related fatalism, and modesty, no perceived need for the screening, poor English proficiency, and mistrust of the American healthcare system. The results also indicated that doctors’ screening recommendations and access to Korean doctors positively influence KAs’ decision to participate in CRC screening. Public health social workers should consider integrating age- and gender-specific cultural contexts when developing interventions and programs for CRC screening targeted to older KAs.
A quantitative method to detect non-antithrombin-binding 3-O-sulfated units in heparan sulfate

Heparan sulfate is synthesized by most animal cells and interacts with numerous proteins via specific sulfation motifs to regulate various physiological processes. Various 3-O-sulfated motifs are considered to be key in controlling the binding specificities to the functional proteins. One such motif synthesized by 3-O-sulfotransferase-1 (3OST-1) serves as a binding site for antithrombin (AT) and has been thoroughly studied because of its pharmacological importance. However, the physiological roles of 3-O-sulfates produced by other 3OST isoforms, which do not bind AT, remain obscure, in part due to the lack of a standard method to analyze this rare modification. This study aims to establish a method for quantifying 3-O-sulfated components of heparan sulfate, focusing on non-AT-binding units. We previously examined the reaction products of human 3OST isoforms and identified five 3-O-sulfated components, including three non-AT-binding disaccharides and two AT-binding tetrasaccharides, as digestion products of heparin lyases. In this study, we prepared these five components as a standard saccharide for HPLC analysis. Together with eight non-3-O-sulfated disaccharides, a standard mixture of 13 units was prepared. Using reverse-phase ion-pair HPLC with a postcolumn fluorescent labeling system, the separation conditions were optimized to quantify the 13 units. Finally, we analyzed the compositional changes of 3-O-sulfated units in heparan sulfate from P19 cells before and after neuronal differentiation. We successfully detected the 3-O-sulfated units specifically expressed in the differentiated neurons. This is the first report that shows the quantification of three non-AT-binding 3-O-sulfated units and establishes a new approach to explore the physiological functions of 3-O-sulfate.
Secondary analysis of gut hormone data from children with and without in utero exposure to gestational diabetes: Differences in the associations among ghrelin, GLP‐1, and insulin secretion

Intrauterine exposure to gestational diabetes mellitus (GDM) increases risk for type 2 diabetes (T2D). Ghrelin and GLP‐1 have opposite functions in nutritional homeostasis and are associated with insulin secretion, but it is not known if individuals exposed to GDM exhibit dysregulation in these associations.
Inhibiting the P2X4 Receptor Suppresses Prostate Cancer Growth In Vitro and In Vivo, Suggesting a Potential Clinical Target

Prostate cancer (PCa) is the most frequently diagnosed cancer in men, causing considerable morbidity and mortality. The P2X4 receptor (P2X4R) is the most ubiquitously expressed P2X receptor in mammals and is positively associated with tumorigenesis in many cancer types. However, its involvement in PCa progression is less understood. We hypothesized that P2X4R activity enhanced tumour formation by PCa cells. We showed that P2X4R was the most highly expressed, functional P2 receptor in these cells using quantitative reverse transcription PCR (RT-PCR) and a calcium influx assay. The effect of inhibiting P2X4R on PCa (PC3 and C4-2B4 cells) viability, proliferation, migration, invasion, and apoptosis were examined using the selective P2XR4 antagonists 5-BDBD and PSB-12062. The results demonstrated that inhibiting P2X4R impaired the growth and mobility of PCa cells but not apoptosis. In BALB/c immunocompromised nude mice inoculated with human PC3 cells subcutaneously, 5-BDBD showed anti-tumourigenic effects. Finally, a retrospective analysis of P2RX4 expression in clinical datasets (GDS1439, GDS1746, and GDS3289) suggested that P2X4R was positively associated with PCa malignancy. These studies suggest that P2X4R has a role in enhancing PCa tumour formation and is a clinically targetable candidate for which inhibitors are already available and have the potential to suppress disease progression.
Metformin induces apoptosis and inhibits migration by activating the AMPK/p53 axis and suppressing PI3K/AKT signaling in human cervical cancer cells

Human cervical cancer is the fourth most common malignancy among women worldwide, and it is expected to result in 460,000 deaths per year by 2040. Moreover, patients with cervical cancer often display drug resistance and severe side effects; therefore, the development of effective novel chemotherapeutic agents is important. In the present study, the effects of metformin, a first-line therapeutic drug for type 2 diabetes mellitus, were evaluated in cervical cancer. Compared with the control group, metformin significantly inhibited cell viability and migration, and induced apoptosis and cell cycle arrest in human cervical cancer cell lines (CaSki and HeLa). Following metformin treatment, the protein expression levels of p-AMP-activated protein kinase (p-AMPK), which promotes cell death, and the tumor suppressor protein p-p53 were remarkably upregulated in CaSki and C33A cells compared with the control group. Furthermore, compared with the control group, metformin significantly suppressed the PI3K/AKT signaling pathway in CaSki, C33A and HeLa cells. Compound C (an AMPK inhibitor) significantly reversed the effects of metformin on CaSki, C33A and HeLa cell viability, and AMPK and p53 phosphorylation. The results of the present study suggested that metformin induced AMPK-mediated apoptosis, thus metformin may serve as a chemotherapeutic agent for human cervical cancer.
Diversity Assessment of Toxic Cyanobacterial Blooms during Oxidation

Fresh-water sources of drinking water are experiencing toxic cyanobacterial blooms more frequently. Chemical oxidation is a common approach to treat cyanobacteria and their toxins. This study systematically investigates the bacterial/cyanobacterial community following chemical oxidation (Cl2, KMnO4, O3, H2O2) using high throughput sequencing. Raw water results from high throughput sequencing show that Proteobacteria, Actinobacteria, Cyanobacteria and Bacteroidetes were the most abundant phyla. Dolichospermum, Synechococcus, Microcystis and Nostoc were the most dominant genera. In terms of species, Dolichospermum sp.90 and Microcystis aeruginosa were the most abundant species at the beginning and end of the sampling, respectively. A comparison between the results of high throughput sequencing and taxonomic cell counts highlighted the robustness of high throughput sequencing to thoroughly reveal a wide diversity of bacterial and cyanobacterial communities. Principal component analysis of the oxidation samples results showed a progressive shift in the composition of bacterial/cyanobacterial communities following soft-chlorination with increasing common exposure units (CTs) (0–3.8 mg·min/L). Close cyanobacterial community composition (Dolichospermum dominant genus) was observed following low chlorine and mid-KMnO4 (287.7 mg·min/L) exposure. Our results showed that some toxin producing species may persist after oxidation whether they were dominant species or not. Relative persistence of Dolichospermum sp.90 was observed following soft-chlorination (0.2–0.6 mg/L) and permanganate (5 mg/L) oxidation with increasing oxidant exposure. Pre-oxidation using H2O2 (10 mg/L and one day contact time) caused a clear decrease in the relative abundance of all the taxa and some species including the toxin producing taxa. These observations suggest selectivity of H2O2 to provide an efficient barrier against toxin producing cyanobacteria entering a water treatment plant.
Flame studies of conventional and alternative jet fuels and their surrogates

Laminar flame speeds and extinction limits of premixed and nonpremixed flames of conventional jet fuels, such as jet propellant 7 and jet propellant 8, and alternative jet fuels, such as synthetic and bioderived, were determined in the counterflow configuration at atmospheric pressure and elevated unburned reactant temperature. The results were compared against those of flames of n-decane and n-dodecane, both being candidate components of jet fuel surrogates. Results indicate that jet propellant 8/air and jet propellant 7/air flames exhibit lower propagation speeds and resistance to extinction compared with flames of alternative fuels. The reduced reactivities of jet propellant 8/air and jet propellant 7/air flames are caused by the alkylcycloparaffins and alkylbenzenes that are present in notable quantities in conventional jet fuels. The combustion characteristics of bioderived jet fuels were found to be indistinguishable from those produced synthetically via the Fischer–Tropsch process. The phenomena of flame propagation and extinction were modeled using n-decane and n-dodecane flames, for which kinetic models are available and for which the molecular weight is representative of that of practical jet fuels. Sensitivity analysis was performed, and results revealed that, compared with flame propagation, flame extinction is, in general, more sensitive to kinetics and diffusion, especially under nonpremixed conditions.
Kinetics of changes in gene and microRNA expression related with muscle inflammation and protein degradation following LPS-challenge in weaned piglets

To test the dynamic changes of the expression of genes and microRNA in the gastrocnemius muscle after LPS challenge, 36 piglets were assigned to a control group (slaughtered 0 h after saline injection) and LPS groups (slaughtered at 1 h, 2 h, 4 h, 8 h, and 12 h after LPS treatment, respectively). After LPS treatment, the mRNA expression of IL-1β, IL-6, and TNF-α reached maximal levels at 1 h, 2 h, and 1 h, respectively (P < 0.05), and mRNA expression of TLR4, NODs, muscle-specific ring finger 1, and muscle atrophy F-box peaked at 12 h (P < 0.05). Moreover, the expression of miR-122, miR-135a, and miR-370 reduced at 1 h, 1 h, and 2 h, respectively (P < 0.05), and miR-34a, miR-224, miR-132, and miR-145 reached maximum expression levels at 1 h, 1 h, 2 h, and 4 h, respectively (P < 0.05). These results suggested that mRNA expression of pro-inflammatory cytokines was elevated in the early stage, mRNA expression of genes related to TLR4 and NODs signaling pathways and protein degradation increased in the later phase, and the expression of microRNA related to muscle inflammation and protein degradation changed in the early stage after LPS injection.
Impact of lymph node staging systems in predicting outcome in patients with ampullary cancer

Backgrounds/Aims Lymph node (LN) metastasis though, is a poor prognostic factor for ampullary carcinoma (APC), the impact of Lymph node ratio (LNR) and Logarithm odds of positive lymph node (LODDS) in the long-term survival remains controversial. We evaluated the factors affecting the long-term outcome in APC patients with emphasis on LNR and LODDS. Methods The prospectively collected data of 198 patients who underwent pancreatoduodenectomy for APC was analyzed after excluding 12 patients for various reasons. Factors affecting Disease specific survival (DSS) and Recurrence free survival (RFS) were analyzed with special reference to LN positivity, LNR and LODDS. Results Out of 186, 117 (62.9%) patients were alive at a median follow-up of 39.5 months and 72 (38.7%) developed recurrence. The overall 5-year DSS was 59.3% & RFS 54.9%. Univariate analysis showed T-stage, tumor differentiation, perineural invasion, LN positivity, LNR and LODDS was significantly affected DSS and RFS. On multivariate analysis, perineural invasion, LN positivity, LNR and LODDS lost its significance for DSS and RFS. AUC for prediction of DSS and RFS for LNR was 0.654 (p<0.001) & 0.629 (p=0.003) respectively and for LODDS, it was 0.697 (p<0.001) & 0.677 (p=0.001) respectively. Sensitivity and specificity of LNR (0.1) for DSS were 37.7% & 83.8% and for RFS were 36.1% & 83.3%; for LODDS (−1.00), sensitivity and specificity for DSS was 62.3% and 67.5% and for RFS it was 59.7% and 66.7% respectively. Conclusions LNR and LODDS although independently seem to affect the RFS and DSS, albeit have a low sensitivity and specificity in predicting DSS and RFS.
Food-Derived Opioid Peptides in Human Health: A Review

World Health Organization data suggest that stress, depression, and anxiety have a noticeable prevalence and are becoming some of the most common causes of disability in the Western world. Stress-related disorders are considered to be a challenge for the healthcare system with their great economic and social impact. The knowledge on these conditions is not very clear among many people, as a high proportion of patients do not respond to the currently available medications for targeting the monoaminergic system. In addition, the use of clinical drugs is also associated with various side effects such as vomiting, dizziness, sedation, nausea, constipation, and many more, which prevents their effective use. Therefore, opioid peptides derived from food sources are becoming one of the safe and natural alternatives because of their production from natural sources such as animals and plant proteins. The requirement for screening and considering dietary proteins as a source of bioactive peptides is highlighted to understand their potential roles in stress-related disorders as a part of a diet or as a drug complementing therapeutic prescription. In this review, we discussed current knowledge on opioid endogenous and exogenous peptides concentrating on their production, purification, and related studies. To fully understand their potential in stress-related conditions, either as a drug or as a therapeutic part of a diet prescription, the need to screen more dietary proteins as a source of novel opioid peptides is emphasized.
Bleomycin A5 suppresses Drp1-mediated mitochondrial fission and induces apoptosis in human nasal polyp-derived fibroblasts

Intralesional injection of bleomycin-A5 (BLE-A5) is a novel treatment for nasal polyps. Our previous study clarified that BLE-A5 could induce nasal polyp-derived fibroblast (NPDF) apoptosis in nasal polyps. However, the detailed mechanisms are still unclear. The present study aimed to determine the effects of BLE-A5 on NPDF mitochondrial dynamics and provide a theoretical basis for the local application of BLE-A5 to treat nasal polyps. In the present study, an in vitro nasal polyp tissue culture model was used to define the BLE-A5 target cell type in nasal polyps. NPDF primary cell culture was used to study the effects of BLE-A5 on the mitochondrial dynamic-related mechanism. The results showed that BLE-A5 treatment of NPDFs caused mitochondrial-mediated apoptosis. Dynamin-related protein 1 (Drp1) was shown to be altered in BLE-A5-treated NPDFs. Drp1 knockdown increased the sensitivity of NPDFs to BLE-A5 and exacerbated mitochondrial dysfunction. BLE-A5 decreased cyclin B1-CDK1 complex-mediated phosphorylation of Drp1 and inhibited Drp1-mediated mitophagy in NPDFs. Overall, the present study concluded that BLE-A5 mainly induces NPDF apoptosis in nasal polyps. BLE-A5 regulates the mitochondria by inhibiting Drp1 activation, resulting in NPDF mitochondrial dynamic disorder and apoptosis.