Does the Internet Provide Quality Information on Metoidioplasty? Using the Modified Ensuring Quality Information for Patients Tool to Evaluate Artificial Intelligence-Generated and Online Information on Metoidioplasty.

BACKGROUND: Public interest in gender affirmation surgery has surged over the last decade. This spike in interest, combined with extensive free online medical knowledge, has led many to the Internet for more information on this complicated procedure. This study aimed to evaluate the quality of online information on metoidioplasty. METHODS: Google Trends in searches on "metoidioplasty" from 2004 to present were assessed. "metoidioplasty" was searched on three popular search engines (Google, Yahoo, and Bing), and the first 100 websites from each search were extracted for inclusion (Fig. 1). Exclusion criteria included duplicates, websites requiring fees, photo libraries, and irrelevant websites. Websites were assigned a score (out of 36) using the modified Ensuring Quality Information for Patients (EQIP) instrument, which grades patient materials based on content (18), identification (6), and structure (12). ChatGPT was also queried for metoidioplasty-related information and responses were analyzed using EQIP. RESULTS: Google Trends analysis indicated relative search interest in "metoidioplasty" has more than quadrupled since 2013(Fig. 2). Of the 93 websites included, only 2 received an EQIP score greater than 27 (6%). Website scores ranged from 7 to 33, with a mean of 18.6 ± 4.8. Mean scores were highest for websites made by health departments (22.3) and lowest for those made by encyclopedias and academic institutions (16.0). Websites with the highest frequency were research articles, web portals, hospital websites, and private practice sites, which averaged scores of 18.2, 19.7, 19.0, and 17.8, respectively. Health department sites averaged the highest content points (11.25), and academic institutions averaged the lowest (5.5). The average content point across all websites was 7.9 of 18. ChatGPT scored a total score of 29: 17 content, 2 identification, and 10 structures. The artificial intelligence chatbot scored the second highest score among all included online resources. CONCLUSIONS: Despite the continued use of search engines, the quality of online information on metoidioplasty remains exceptionally poor across most website developers. This study demonstrates the need to improve these resources, especially as interest in gender-affirming surgery continues to grow. ChatGPT and other artificial intelligence chatbots may be efficient and reliable alternatives for those seeking to understand complex medical information.

Forces required to dynamize sliding screws in gamma nail and selfdynamizable internal fixator.

BACKGROUND: Single limb support phase of the gait-cycle in patients who are treated for a pertrochanteric fracture is characterized by transversal loads acting on the lag screw, tending to block its dynamization. If the simultaneous axial force overcomes transversal loads of the sliding screw, the dynamization can still occur. METHODS: Biomechanical investigation was performed for three types of dynamic implants: Gamma Nail, and two types of Selfdynamizable Internal Fixators (SIF) - SIF-7 (containing two 7 mm non-cannulated sliding screws), and SIF-10 (containing one 10 mm cannulated sliding screw). Contact surface between the stem and the sliding screws is larger in SIF implants than in Gamma Nail, as the stem of Gamma Nail is hollow. A special testing device was designed for this study to provide simultaneous application of a controlled sliding screws bending moment and a controlled transversal load on sliding screws (Qt) without using of weights. Using each of the implants, axial forces required to initiate sliding screws dynamization (Qa) were applied and measured using a tensile testing machine, for several values of sliding screws bending moment. Standard least-squares method was used to present the results through the linear regression model. RESULTS: Positive correlation between Qt and Qa was confirmed (p < 0.05). While performing higher bending moments in all the tested implants, Qa was higher than it could be provided by the body weight. It was the highest in Gamma Nail, and the lowest in SIF-10. CONCLUSIONS: A larger contact surface between a sliding screw and stem results in lower forces required to initiate dynamization of a sliding screw. Patients treated for a pertrochanteric fracture by a sliding screw internal fixation who have longer femoral neck or higher body weight could have different programme of early postoperative rehabilitation than lighter patients or patients with shorter femoral neck.

Investigation of the OAM EM wave tissue irradiation at millimeter-wave frequencies.

Recently, there has been an increase of interest in the use of electromagnetic (EM) waves with helical wavefronts, known as the orbital angular momentum (OAM) waves. Applications in the field of biomedicine have been foreseen, such as medical imaging and diagnosis, deep-tissue imaging, biosensing, and communication with medical implants. Other possible applications include various localized tissue treatments or tissue ablation. The available references mainly study the interaction of OAM light with biological structures, offering some insights into the biophotonics effects, but without the investigation of how to plan tissue exposures or how to estimate the EM field parameters in a particular case of application. We use the previously developed short dipole modeling of OAM EM fields to study the above problems by altering the OAM beam parameters and the distance from the target tissue. The results could guide the design of components and devices based on OAM EM waves.

Applying machine learning in the investigation of the link between the high-velocity streams of charged solar particles and precipitation-induced floods.

This study explores a possible link between solar activity and floods caused by precipitation. For this purpose, discrete blocks of data for 89 separate flood events in Europe in the period 2009-2018 were used. Solar activity parameters with a time lag of 0-11 days were used as input data of the model, while precipitation data in the 12 days preceding the flood were used as output data. The level of randomness of the input and output time series was determined by correlation analysis, while the potential causal relationship was established by applying machine learning classification predictive modeling. A total of 25 distinct machine-learning algorithms and four model ensembles were applied. It was shown that in 81% of cases, the designed model could explain the occurrence or absence of precipitation-induced floods 9 days in advance. Differential proton flux in the 0.068-0.115 MeV and integral proton flux > 2.5 MeV were found to be the most important factors for forecasting precipitation-induced floods. The study confirmed that machine learning is a valuable technique for establishing nonlinear relationships between solar activity parameters and the onset of floods induced by precipitation.

The Human Soluble NKG2D Ligand Differentially Impacts Tumorigenicity and Progression in Temporal and Model-Dependent Modes.

NKG2D is an activating receptor expressed by all human NK cells and CD8 T cells. Harnessing the NKG2D/NKG2D ligand axis has emerged as a viable avenue for cancer immunotherapy. However, there is a long-standing controversy over whether soluble NKG2D ligands are immunosuppressive or immunostimulatory, originating from conflicting data generated from different scopes of pre-clinical investigations. Using multiple pre-clinical tumor models, we demonstrated that the impact of the most characterized human solid tumor-associated soluble NKG2D ligand, the soluble MHC I chain-related molecule (sMIC), on tumorigenesis depended on the tumor model being studied and whether the tumor cells possessed stemness-like properties. We demonstrated that the potential of tumor formation or establishment depended upon tumor cell stem-like properties irrespective of tumor cells secreting the soluble NKG2D ligand sMIC. Specifically, tumor formation was delayed or failed if sMIC-expressing tumor cells expressed low stem-cell markers; tumor formation was rapid if sMIC-expressing tumor cells expressed high stem-like cell markers. However, once tumors were formed, overexpression of sMIC unequivocally suppressed tumoral NK and CD8 T cell immunity and facilitated tumor growth. Our study distinguished the differential impacts of soluble NKG2D ligands in tumor formation and tumor progression, cleared the outstanding controversy over soluble NKG2D ligands in modulating tumor immunity, and re-enforced the viability of targeting soluble NKG2D ligands for cancer immunotherapy for established tumors.

Are farmers motivated to select for heat tolerance? Linking attitudinal factors, perceived climate change impacts, and social trust to farmers' breeding desires.

This study provides an understanding of dairy farmers' willingness to include heat tolerance in breeding goals and the modulating effect of sociopsychological factors and farm profile. A survey instrument including a choice experiment was designed to specifically address the trade-off between heat tolerance and milk production level. A total of 122 farmers across cattle, goat, and sheep farms were surveyed face-to-face. The results of the experiment show that most farmers perceive that heat stress and climate change are increasingly important problems, and that farming communities should invest more in generating knowledge and resources on mitigation strategies. However, we found limited initial support for selection for heat tolerance. This attitude changed when farmers were presented with objective information on the benefits and limitations of the different breeding choices, after which most farmers supported selection for heat tolerance, but only if doing so would compromise milk production gains to a small extent. Our results show that farmers' selection choices are driven by the interactions between heat stress risk perception, attitudes toward breeding tools, social trust, the species reared, and farm production level. In general, farmers willing to support selection of heat-tolerant animals are those with positive attitudes toward genetic values and genomic information and a strong perception of climate change and heat stress impacts on farms. On the contrary, negative support for selection for heat tolerance is found among farmers with high milk production levels; high trust in farming magazines, livestock farmers' associations, and veterinarians; and low trust in environmental and animalist groups.

Single-cell Analysis Reveals Inter- and Intratumour Heterogeneity in Metastatic Breast Cancer.

Metastasis is the leading cause of cancer-related deaths of breast cancer patients. Some cancer cells in a tumour go through successive steps, referred to as the metastatic cascade, and give rise to metastases at a distant site. We know that the plasticity and heterogeneity of cancer cells play critical roles in metastasis but the precise underlying molecular mechanisms remain elusive. Here we aimed to identify molecular mechanisms of metastasis during colonization, one of the most important yet poorly understood steps of the cascade. We performed single-cell RNA-Seq (scRNA-Seq) on tumours and matched lung macrometastases of patient-derived xenografts of breast cancer. After correcting for confounding factors such as the cell cycle and the percentage of detected genes (PDG), we identified cells in three states in both tumours and metastases. Gene-set enrichment analysis revealed biological processes specific to proliferation and invasion in two states. Our findings suggest that these states are a balance between epithelial-to-mesenchymal (EMT) and mesenchymal-to-epithelial transitions (MET) traits that results in so-called partial EMT phenotypes. Analysis of the top differentially expressed genes (DEGs) between these cell states revealed a common set of partial EMT transcription factors (TFs) controlling gene expression, including ZNF750, OVOL2, TP63, TFAP2C and HEY2. Our data suggest that the TFs related to EMT delineate different cell states in tumours and metastases. The results highlight the marked interpatient heterogeneity of breast cancer but identify common features of single cells from five models of metastatic breast cancer.

A Weight of Evidence approach to support the assessment of the quality of Manila clam farming sites in a coastal lagoon.

Aquaculture productivity in coastal lagoons is endangered by a complex interplay of anthropogenic and environmental factors, amplified by the effects of climate change in these sensitive areas. To reach a more comprehensive assessment of farming sites quality, a quantitative Weight of Evidence approach (QWoE) is applied for the first time to data collected at four Manila clam (R. philippinarum) farming sites in the Venice lagoon (Italy). This included sediment quality, chemical bioaccumulation, and biological responses. Results revealed a greater hazard for sites closer to the open sea. In these areas, the combination of sediment characteristics and a higher frequency of salinity and temperature stress could explain the alterations measured at a transcriptional and biomarker level. The findings demonstrate that a QWoE approach that integrates multiple sources of evidence should also include physicochemical conditions in order to better understand the impacts of human activities and other stressors on clam aquaculture productivity.

Nitric oxide, thyroglobulin, and calcitonin: unraveling the nature of thyroid nodules.

Background: Thyroid nodules (TN) are localized morphological changes in the thyroid gland and can be benign or malignant. Objective: The present study investigates the relationships between biochemical markers in serum (s) and their homologs in washout (w) after fine-needle aspiration biopsy (FNAB) of the TN of interest and their correlation with cytology specimen findings. Methods: We investigated the relationships between serum biochemical markers nitric oxide (NO), thyroglobulin (TG), and calcitonin (CT), their homologs in washout after FNAB of the TN of interest, and cytology findings of biopsy samples classified according to the Bethesda system for thyroid cytopathology in this study, which included 86 subjects. Results: Washout TG (TGw) level positively correlates with the cytology finding of the biopsy. A higher level of TGw correlates with higher categories of the Bethesda classification and indicates a higher malignant potential. The levels of serum NO (NOs), serum TG (TGs), serum CT (CTs), and washout CT (CTw) do not correlate with the cytology finding of the biopsy, and the higher levels of washout NO (NOw) correspond to the more suspicious ultrasound findings. Conclusion: The findings of our study suggest that TGw and NOw could be used as potential predictors of malignancy in TN.

Metasurfaces integrated with a single-mode waveguide array for off-chip wavefront shaping.

Integration of metasurfaces and SOI (silicon-on-insulator) chips can leverage the advantages of both metamaterials and silicon photonics, enabling novel light shaping functionalities in planar, compact devices that are compatible with CMOS (complementary metal-oxide-semiconductor) production. To facilitate light extraction from a two-dimensional metasurface vertically into free space, the established approach is to use a wide waveguide. However, the multi-modal feature of such wide waveguides can render the device vulnerable to mode distortion. Here, we propose a different approach, where an array of narrow, single-mode waveguides is used instead of a wide, multi-mode waveguide. This approach tolerates nano-scatterers with a relatively high scattering efficiency, for example Si nanopillars that are in direct contact with the waveguides. Two example devices are designed and numerically studied as demonstrations: the first being a beam deflector that deflects light into the same direction regardless of the direction of input light, and the second being a light-focusing metalens. This work shows a straightforward approach of metasurface-SOI chip integration, which could be useful for emerging applications such as metalens arrays and neural probes that require off-chip light shaping from relatively small metasurfaces.

Metformin promotes antitumor activity of NK cells via overexpression of miRNA-150 and miRNA-155.

OBJECTIVES: Metformin, an oral anti-diabetic drug, is known to possess a powerful antitumor effect by modulating the tumor-immune interaction. The precise influence of metformin on natural killer (NK) cells, a crucial innate immunity player, is not completely understood. In our study, analyses of the effect of metformin on the NK cell functional phenotype were performed, and the potential mechanisms underlying it were investigated. METHODS: BALB/C wild type mice were treated with metformin, and the functional phenotype of splenocytes and potential underlying mechanisms were investigated. RESULTS: Metformin significantly boosts NK cell cytotoxicity and the percentage of NKp46+, FasL+, and interferon (IFN)-γ+ NK cells while decreasing interleukin (IL)-10 producing NK cells. Our research also demonstrated that the simultaneous administration of metformin and 1-methyl-DL-tryptophan (1-MT), a specific inhibitor of indoleamine 2,3-dioxygenase (IDO), significantly increased the NK cells synthesis of IFN-γ, IL-17, perforin, and FasL and NKp46 expression. These findings imply that metformin potentiates NK cell cytotoxicity through mechanisms other than IDO blockade. Metformin administration strongly increased the expression of immunostimulatory microRNA (miRNA)-150 and miRNA-155, while decreasing the expression of immunosuppressive miRNA-146a. CONCLUSIONS: These findings suggest that metformin can directly potentiate NK cell activation and cytotoxicity. This research may contribute to dissecting key mechanisms of metformin exerting antitumor activity to advance the use of metformin as an antitumor agent.

Long-Term Renal Function after Catheter Ablation of Atrial Fibrillation.

Background: Atrial fibrillation (AF) is associated with the development and progression of chronic kidney disease (CKD). This study evaluated the impact of long-term rhythm outcome after catheter ablation (CA) of AF on renal function. Methods and results: The study group included 169 consecutive patients (the mean age was 59.6 ± 10.1 years, 61.5% were males) who underwent their first CA of AF. Renal function was assessed by eGFR (using the CKD-EPI and MDRD formulas), and by creatinine clearance (using the Cockcroft-Gault formula) in each patient before and 5 years after index CA procedure. During the 5-year follow-up after CA, the late recurrence of atrial arrhythmia (LRAA) was documented in 62 patients (36.7%). The mean eGFR, regardless of which formula was used, significantly decreased at 5 years following CA in patients with LRAA (all p < 0.05). In the arrhythmia-free patients, the mean eGFR at 5 years post-CA remained stable (for the CKD-EPI formula: 78.7 ± 17.3 vs. 79.4 ± 17.4, p = 0.555) or even significantly improved (for the MDRD formula: 74.1 ± 17.0 vs. 77.4 ± 19.6, p = 0.029) compared with the baseline. In the multivariable analysis, the independent risk factors for rapid CKD progression (decline in eGFR > 5 mL/min/1.73 m2 per year) were the post-ablation LRAA occurrence (hazard ratio 3.36 [95% CI: 1.25-9.06], p = 0.016), female sex (3.05 [1.13-8.20], p = 0.027), vitamin K antagonists (3.32 [1.28-8.58], p = 0.013), or mineralocorticoid receptor antagonists' use (3.28 [1.13-9.54], p = 0.029) after CA. Conclusions: LRAA after CA is associated with a significant decrease in eGFR, and it is an independent risk factor for rapid CKD progression. Conversely, eGFR in arrhythmia-free patients after CA remained stable or even improved significantly.

Development of Selective ADAMTS-5 Peptide Substrates to Monitor Proteinase Activity.

The dysregulation of proteinase activity is a hallmark of osteoarthritis (OA), a disease characterized by progressive degradation of articular cartilage by catabolic proteinases such as a disintegrin and metalloproteinase with thrombospondin type I motifs-5 (ADAMTS-5). The ability to detect such activity sensitively would aid disease diagnosis and the evaluation of targeted therapies. Förster resonance energy transfer (FRET) peptide substrates can detect and monitor disease-related proteinase activity. To date, FRET probes for detecting ADAMTS-5 activity are nonselective and relatively insensitive. We describe the development of rapidly cleaved and highly selective ADAMTS-5 FRET peptide substrates through in silico docking and combinatorial chemistry. The lead substrates 3 and 26 showed higher overall cleavage rates (∼3-4-fold) and catalytic efficiencies (∼1.5-2-fold) compared to the best current ADAMTS-5 substrate ortho-aminobenzoyl(Abz)-TESE↓SRGAIY-N-3-[2,4-dinitrophenyl]-l-2,3-diaminopropionyl(Dpa)-KK-NH2. They exhibited high selectivity for ADAMTS-5 over ADAMTS-4 (∼13-16-fold), MMP-2 (∼8-10-fold), and MMP-9 (∼548-2561-fold) and detected low nanomolar concentrations of ADAMTS-5.

Evaluation of outdoor thermal comfort conditions: evidence from the Serbian major ski resort over the last 30 years.

The study aims to present reliable information about thermal conditions and their impacts on visitors to ski travel destinations. Mountain tourism areas are specific since high altitudes affect the ambient weather conditions which can affect different types of human activities. In this paper, the thermal comfort and its changes in Kopaonik Mountain, the most popular ski resort in Serbia over the last 30 years, have been evaluated. Information about thermal comfort is presented by using the Universal Thermal Climate Index (UTCI), physiologically equivalent temperature (PET), and modified physiologically equivalent temperature (mPET) in 3-h resolution for the period 1991-2020. The results indicate prevailing cold stress all year round. Days with moderate, strong, and very strong heat stress were not recorded. Strong and extreme cold stress prevailed during winter, while slight and moderate cold stress prevailed during summer. Transitional seasons were very cold, but autumn was more comfortable than spring. The occurrence of days with neutral and slightly warm/cool conditions is concentrated in the summer months. However, summer is not used enough for tourism because the choice of tourists to stay at Kopaonik is not primarily based on favorable bioclimatic conditions, but on resources for winter tourism. With global warming, the annual number of thermally favorable days has been increasing, while the number of days with extreme and strong cold stress is decreasing. Continuing this trend can significantly influence tourism in the future, and therefore, new strategies in ski resorts will be required to adapt to the changing climate.

Rise of Acellular Dermal Matrix: Cost Consciousness, Industry Payment, and Publication Productivity.

BACKGROUND: Despite high cost and lack of FDA approval for breast surgery, acellular dermal matrix (ADM) has become commonplace in reconstructive surgery and has been the focus of more than 500 plastic surgery publications since its wide adoption. We hypothesized that ADM-related academic output would correlate with public interest and industry funding. STUDY DESIGN: All PubMed-indexed studies focusing on ADM in 11 plastic surgery journals were included (n = 535). Data on industry funding to the 17 most productive authors were extracted from the Open Payments Database. Google Trends in "breast surgery cost" and related terms were queried. Relationships among publication quantity, author industry funding, and public interest were analyzed by Pearson's correlation and linear regression. RESULTS: The most published authors produced 8 qualifying publications on average (range 5 to 17), with 80% focused on breast surgery. These individuals grossed a total of $19 million industry dollars overall with $17 million (89%) in nonconsulting compensation from ADM-producing companies (NC-ADM). Individual total compensation and NC-ADM compensation, by quartile, were $194,000/$320,000/$1.25 million and $17,000/$210,000/$1.1 million, respectively. These variables showed strong correlation with individual publication rate with a linear regression coefficient of $110K in NC-ADM per publication (p < 0.01). Authors disclosed funding in a mean ± SD of 65 ± 26% of their work with strong correlation between disclosure and NC-ADM (p < 0.01). Google "breast surgery cost" search volume has grown rapidly in significant correlation with ADM publications (p = 0.02). CONCLUSIONS: This study demonstrates significant correlation between ADM-related publication, industry funding, funding disclosure, and public interest. Education in the potential for such relationships and the importance of objectivity in plastic surgery warrants discussion.

Significance of the Work Environment and Personal Resources for Employees' Well-Being at Work in the Hospitality Sector.

The aim of the study was to investigate whether different elements of the work environment (manifested by job demands, job control, and social support) and personal resources were linked to employees' well-being at work. Based on data gathered from 574 employees in the hospitality industry in Serbia, it was also tested if personal resources, expressed through self-efficacy, hope, optimism, and resilience, could moderate the relationship between work environment and employees' well-being at work. Correlation analyses showed that high job demands had negative effects on employees' well-being, causing negative emotional reactions to their job, while job control and social support developed positive relationships with positive employees' well-being. The moderating effect analysis found that personal resources can fully moderate the relationship between job demands and well-being at work, and job control and well-being at work. On the other side, personal resources were not a significant moderator in the relationship between social support and well-being at work, indicating that even when employees have adequate personal resources, they are not enough to decrease the negative effects of lack of social support on employees' well-being at work. This shows how important the support of supervisors and colleagues is for employees in hospitality.

Recent Advances in Electrochemical Sensors for Caffeine Determination.

The determination of target analytes at very low concentrations is important for various fields such as the pharmaceutical industry, environmental protection, and the food industry. Caffeine, as a natural alkaloid, is widely consumed in various beverages and medicines. Apart from the beneficial effects for which it is used, caffeine also has negative effects, and for these reasons it is very important to determine its concentration in different mediums. Among numerous analytical techniques, electrochemical methods with appropriate sensors occupy a special place since they are efficient, fast, and entail relatively easy preparation and measurements. Electrochemical sensors based on carbon materials are very common in this type of research because they are cost-effective, have a wide potential range, and possess relative electrochemical inertness and electrocatalytic activity in various redox reactions. Additionally, these types of sensors could be modified to improve their analytical performances. The data available in the literature on the development and modification of electrochemical sensors for the determination of caffeine are summarized and discussed in this review.

Chemometric Approach to the Composition of Flavonoid Compounds and Phenolic Acids and Antioxidant Potential of Artemisia Species from Different Habitats.

Four Artemisia species from Serbia were selected for the study: A. annua L., A. absinthium L., A. vulgaris L. and A. scoparia Waldst. et Kit. because of the proven excellent action in treating certain medical conditions and diseases. A. absinthium L., A. vulgaris L., A. annua L. and A. scoparia Waldst. et Kit. collected from different habitats across Serbia (48 samples in total) were studied from the statistical aspect considering the phenolic and flavonoid contents, compositions, and antioxidant activities of methanol extracts in correlation with the soil type. The components were identified using HPLC (High Performance Liquid Chromatography), while antioxidant activities were determined by seven assays (TP (Total phenolic content), TF (Total flavonoid content), DPPH (2,2-diphenyl-1-picrylhydrazyl) radical-based, ABTS (2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid)) radical cation-based, FRAP (Ferric Reducing Antioxidant Power), TRP (Total Reducing Power), and CUPRAC (Cupric Reducing Antioxidant Capacity). The results were processed using five statistical methods (PCA (Principal Component Analysis), ANOVA (Analysis of Variance), MANOVA (Multivariate analysis of variance), DA (Discriminant analysis), and AHC (Agglomerative Hierarchical Clustering)). Principal component analysis enabled very well separation of the analyzed Artemisia species based on the content of total phenolics, total flavonoids, and the values obtained from antioxidant tests, but not on the individual compounds identified and quantified by HPLC. The MANOVA analyses showed that for A. scoparia and A. annua there was a significant effect of soil type on the total phenolics, total flavonoids, and antioxidant tests. In contrast, for A. vulgaris and A. absinthium, that effect was not significant. Additional MANOVA analyses showed a significant effect of soil type on phenolic and flavonoid compounds in the case of A. vulgaris, A. annua, and A. absinthium. The overall correct classification rate of all samples of four investigated Artemisia species by the discriminant analysis was 81.25 % using the training sample and 72.92 % the cross-validation results based on TP, TF, and antioxidant tests, but a much lower based on selected compounds identified and quantified by HPLC. MANOVA analyses based on particular Artemisia species show that soil is a significant factor affecting the measurable variables.

A high-throughput drug screen reveals means to differentiate triple-negative breast cancer.

Plasticity delineates cancer subtypes with more or less favourable outcomes. In breast cancer, the subtype triple-negative lacks expression of major differentiation markers, e.g., estrogen receptor α (ERα), and its high cellular plasticity results in greater aggressiveness and poorer prognosis than other subtypes. Whether plasticity itself represents a potential vulnerability of cancer cells is not clear. However, we show here that cancer cell plasticity can be exploited to differentiate triple-negative breast cancer (TNBC). Using a high-throughput imaging-based reporter drug screen with 9 501 compounds, we have identified three polo-like kinase 1 (PLK1) inhibitors as major inducers of ERα protein expression and downstream activity in TNBC cells. PLK1 inhibition upregulates a cell differentiation program characterized by increased DNA damage, mitotic arrest, and ultimately cell death. Furthermore, cells surviving PLK1 inhibition have decreased tumorigenic potential, and targeting PLK1 in already established tumours reduces tumour growth both in cell line- and patient-derived xenograft models. In addition, the upregulation of genes upon PLK1 inhibition correlates with their expression in normal breast tissue and with better overall survival in breast cancer patients. Our results indicate that differentiation therapy based on PLK1 inhibition is a potential alternative strategy to treat TNBC.

Indigo Carmine in a Food Dye: Spectroscopic Characterization and Determining Its Micro-Concentration through the Clock Reaction.

Indigo carmine is a commonly used industrial blue dye. To determine its concentration in a commercially available food dye composed of a mixture of indigo carmine and D-glucose, this paper characterizes it through (ATR, KBr) FTIR micro-Raman as well as UV/Vis and clock: Briggs-Rauscher (BR) oscillatory reaction methods. The indigo carmine was detected in the bulk food dye only by applying micro-Raman spectroscopy, indicating a low percentage of the indigo carmine present. This research provides an improvement in the deviations from the experimental Raman spectrum as calculated by the B97D/cc-pVTZ level of theory one, resulting in a better geometrical optimization of the indigo carmine molecule compared to data within the literature. The analytical curves used to determine indigo carmine concentrations (and quantities) in an aqueous solution of food dye were applied by means of UV/Vis and BR methods. BR yielded significantly better analytical parameters: 100 times lower LOD and LOQ compared to commonly used UV/Vis. The remarkable sensitivity of the BR reaction towards indigo carmine suggests that not only does indigo carmine react in an oscillatory reaction but also its decomposition products, meaning that the multiple oxidation reactions have an important role in the BR's indigo carmine mechanism. The novelty of this research is the investigation of indigo carmine using a clock BR reaction, opening new possibilities to determine indigo carmine in other complex samples (pharmaceutical, food, etc.).