Miracle-dz/UniFAR-FTUs huggingface dataset:
Neutrophil-to-Lymphocyte Ratio in Rectal Cancer—Novel Biomarker of Tumor Immunogenicity During Radiotherapy or Confounding Variable?

The aim of this study was to investigate the predictive value of blood-derived makers of local and systemic inflammatory responses on early and long-term oncological outcomes. A retrospective analysis of patients with locally advanced rectal cancer treated with preoperative long-course 5-fluorouracil-based radiochemotherapy was performed. Differential blood counts before neoadjuvant treatment were extracted from the patients’ electronic charts. Optimal cut-off values for neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and lymphocyte-to-monocyte ratio (LMR) were determined. Potential clinical and hematological prognostic factors for disease-free survival (DFS) were studied using uni- and multivariate analysis. A total of 220 patients were included in the analysis. Median follow-up was 67 months. Five-year DFS and overall survival (OS) were 70% and 85%, respectively. NLR with a cut-off value of 4.06 was identified as optimal to predict DFS events. In multivariate analysis, only tumor volume (HR 0.33, 95% CI (0.14–0.83), p = 0.017) and NLR (HR 0.3, 95% CI (0.11–0.81), p = 0.017) remained significant predictors of DFS. Patients with a good histological response (Dworak 3 and 4) to radiotherapy also had a lower NLR than patients with less pronounced tumor regression (3.0 vs. 4.2, p = 0.015). A strong correlation between primary tumor volume and NLR was seen (Pearson’s r = 0.64, p < 0.001). Moreover, patients with T4 tumors had a significantly higher NLR than patients with T1–T3 tumors (6.6 vs. 3.3, p < 0.001). An elevated pretherapeutic NLR was associated with higher T stage, inferior DFS, and poor pathological response to neoadjuvant radiochemotherapy. A strong correlation between NLR and primary tumor volume was seen. This association is important for the interpretation of study results and for the design of translational studies which are warranted.
Effect of Turkish Propolis on miRNA Expression, Cell Cycle, and Apoptosis in Human Breast Cancer (MCF-7) Cells

Abstract Enriched in flavonoid compounds, phenol acids, and terpene derivatives, propolis has been shown to regulate apoptosis signaling pathways and alter the expression of microRNAs (miRNAs). In the present study, it has been aimed to examine the effects of Turkish propolis on miRNA levels of breast cancer (MCF-7) cells, and its relationship with cell proliferation and apoptosis. Cytotoxic activity of ethanolic propolis extract (EEP) was evaluated using MTT assay. Mechanisms involved in the cytotoxic action of Turkish propolis in MCF-7 cells were investigated with regard to apoptosis and cell cycle using flow cytometry and western blot. Mitochondrial membrane potential (MMP) were evaluated by spectrofluorometric method. miRNA levels were detected by qRT-PCR method. EEP exhibited selective toxicity against MCF-7 cells compared to normal fibroblast cells. EEP increased the cell cycle arrest at the G1 phase. EEP elevated the apoptotic cell death through increasing pro-apoptotic protein levels (p21, Bax, p53, p53-Ser46, and p53-Ser15), decreasing MMP and altering the expression levels of specific tumor suppressors (miR-34, miR-15a, and miR-16-5p) and oncogenic (miR-21) miRNAs. These data support that Turkish propolis may be evaluated as a potential natural agent for new anticancer drugs in future.
Increased Thymidylate Synthase mRNA Concentration in Blood Leukocytes following an Experimental Stressor

Background: While it is well documented that immune responses, e.g. proliferative responses, can be influenced by psychosocial factors, e.g. stress, less is known about the biological mechanisms mediating such influences. The aim of the present investigation was to study the effect of an experimental stressor on mRNA levels in peripheral blood leukocytes of thymidylate synthase (TS), a gene necessary for cell division, while investigating possible individual differences in stress reactivity. Methods: Fifteen healthy subjects were investigated under three experimental conditions: (1) exposure to a computerized mental stressor; (2) relaxation, and (3) control. Measurements included TS mRNA levels, total leukocyte number, leukocyte subtypes, and serum cortisol before (baseline), immediately after, and 1 h after each experimental condition. Results: While no significant differences were found between experimental conditions at baseline in cortisol (p = 0.9) or TS mRNA levels (p = 0.1), significantly higher TS mRNA expression was found immediately after stress compared to pretreatment levels (p < 0.02). Changes in cortisol levels indicated an effect of the experimental stressor, with higher cortisol levels seen immediately after stress as compared to both relaxation (p < 0.01) and control (p < 0.01). Subjects who scored above the median on the Tellegen Absorption Scale showed significantly (p < 0.05) greater increases in cortisol and percentage of lymphocytes and significantly greater decreases in percentage of neutrophil cells after stress. Conclusion: The results suggest that TS mRNA levels in peripheral leukocytes may be sensitive to mental stress and confirm previous findings indicating that subjects scoring high on the personality trait of absorption exhibit greater physiological stress reactivity.
Menadione‐Catalyzed O2– Production by Escherichia coli Cells: Application of Rapid Chemiluminescent Assay to Antimicrobial Susceptibility Testing

This study proposes a novel chemiluminescent assay of bacterial activity. Luminol chemiluminescence (LC) was amplified on addition of menadione to Escherichia coli suspension, and it was effectively inhibited by addition of superoxide dismutase rather than catalase. This fact suggests that H2O2 produced from O2– by superoxide dismutase is decomposed by catalase of E. coli. NAD(P)H:menadione reductase activities in periplasm and cytosol corresponded to the amplification of menadione‐catalyzed LC, and outer and cytoplasmic membranes were only slightly involved in the LC. The total activity and Vmax of NAD(P)H:menadione reductase in the cytoplasm were greater than those in the periplasm. A transient increase in menadione‐catalyzed LC was observed in the exponential phase and the LC decreased in the stationary phase during growth of E. coll Menadione‐catalyzed LC was sensitive to antibiotic action. A decrease in menadione‐catalyzed LC by the impairment of membrane functions and by the inhibition of protein synthesis was observed at 5 min and 3 hr, respectively. These findings suggest the possibility that menadione‐catalyzed luminol chemiluminescent assay is applicable to rapid antimicrobial assay because LC is sensitive to the change in growth and cytotoxic events caused by antimicrobial agents.
Negotiating End-of-Life Decision Making: A Comparison of Japanese and U.S. Residents' Approaches

Purpose To compare Japanese and U.S. resident physicians' attitudes, clinical experiences, and emotional responses regarding making disclosures to patients facing incurable illnesses. Method From September 2003 to June 2004, the authors used a ten-item self-administered anonymous questionnaire in a cross-sectional survey of 103 internal medicine residents at two U.S. sites in Los Angeles, California, and 244 general medical practice residents at five Japanese sites in Central Honshu, Kyushu, Okinawa, Japan. Results The Japanese residents were more likely to favor including the family in disclosing diagnosis (95% versus 45%, p < .001) and prognosis (95% versus 51%, p < .001) of metastatic gastric cancer. Of residents who favored diagnostic or prognostic disclosure to both the patient and family, Japanese residents were more likely to prefer discussion with the family first. Trainees in Japan expressed greater uncertainty about ethical practices related to disclosure of diagnosis or prognosis. Many Japanese and U.S. residents indicated that they had deceived a patient at the request of a family (76% versus 18 %, p < .001), or provided nonbeneficial care (56% versus 72%, p < .05), and many expressed guilt about these behaviors. Conclusions The residents' approaches to end-of-life decision making reflect known cultural preferences related to the role of patients and their families. Although Japanese trainees were more likely to endorse the role of the family, they expressed greater uncertainty about their approach. Difficulty and uncertainty in end-of-life decision making were common among both the Japanese and U.S. residents. Both groups would benefit from ethical training to negotiate diverse, changing norms regarding end-of-life decision making.
Micro-Injection Moulding of Poly(vinylpyrrolidone-vinyl acetate) Binary and Ternary Amorphous Solid Dispersions

Micro-injection moulding (µIM) was used for the production of enteric tablets of plasticised and unplasticised solid dispersions of poly(vinylpyrrolidone-vinyl acetate) (PVPVA), and the effect of the mechanical and thermal treatment on the properties of the dispersions was investigated. The physical state of the systems showed to be unaltered by the µIM step, maintaining the drug in the amorphous state. The dissolution profile of the tablets showed a slower dissolution rate due to the lower surface to volume ratio compared to the extruded strands. The lack of solubility of the doses in the acidic medium as a consequence of the acidity of indomethacin (IND) was observed. However, in neutral pH the drug dissolution showed slower rates without affecting the dissolution extent, showing a potential application for the development of controlled release doses. Overall, the production of tablets of amorphous solid dispersions (ASD), coupling hot-melt extrusion (HME) and µIM, proved to be a successful approach towards a continuous automated manufacturing process to improve the aqueous solubility of poorly water-soluble drugs.
B cell epitopes in the intrinsically disordered regions of neuraminidase and hemagglutinin proteins of H5N1 and H9N2 avian influenza viruses for peptide‐based vaccine development

Avian influenza viruses (AIV) are very active in several parts of the globe and are the cause of huge economic loss for the poultry industry and also human fatalities. Three dimensional modeling was carried out for neuraminidase (NA) and hemagglutinin (HA) proteins of AIV. The C‐score, estimated TM‐Score, and estimated root‐mean‐square deviation (RMSD) score for NA of H5N1 were −1.18, 0.57 ± 0.15, and 9.8 ± 7.6, respectively. The C‐score, estimated TM‐Score, and estimated RMSD score for NA of H9N2 were −1.43, 0.54 ± 0.15, and 10.5 ± 4.6, respectively. The C‐score, estimated TM‐Score, and estimated RMSD score for HA of H5N1 were −0.03, 0.71 ± 0.12, and 7.7 ± 4.3, respectively. The C‐score, estimated TM‐Score, and estimated RMSD score for HA of H9N2 were −0.57, 0.64 ± 0.13, and 8.9 ± 4.6, respectively.
An Energy Efficient Multi-User Asynchronous Wireless Transmitter for Biomedical Signal Acquisition

The paper presents a novel transmitter architecture for short-range asynchronous wireless communication, applicable to simultaneous multi-user wireless acquisition of biological signals. The analog signal, provided from an analog biosensor, is transformed to time information using an Integral Pulse Frequency Modulator (IPFM) as a Time-Encoding Machine. The IPFM generates a time-encoded unipolar pulse train, maintaining the linear dependence of the output pulse distance on analog input voltage. The system enables continuous acquisition of the signals from multiple sensors in which each transmitter has unique feedback loop delay used for multi-user coding. IPFM pulses trigger the Impulse Radio Ultra-Wideband pulse generator directly, providing two ultra-wideband (UWB) pulses per each IPFM pulse. Due to the lack of internal clock signal and microprocessor-free multi-user coding, the circuitry satisfies the requirements of multi-user coding energy efficiency and size reduction, which are crucial demands in biomedical applications. The proposed Time-Encoded UWB (TE-UWB) transmitter is implemented in 0.18 <inline-formula><tex-math notation="LaTeX">$\mu{\text{m}}$</tex-math></inline-formula> CMOS technology. Measurement results of the IPFM transfer function for input voltage ranging from 0.15 to 1.5 <inline-formula><tex-math notation="LaTeX">${\rm V}$</tex-math></inline-formula> are presented, providing the dependence of the IPFM pulse time distance on analog input voltage and power consumption dependence on the input voltage level. For continuous monitoring operation, total power consumption of the transmitter circuitry for the maximum input voltage is 10.8 <inline-formula><tex-math notation="LaTeX">$\mu{\text{W}}$</tex-math></inline-formula>, while for the lowest input voltage it increases to 40.48 <inline-formula><tex-math notation="LaTeX">$\mu{\text{W}}$</tex-math></inline-formula>. The circuit occupies 0.14 <inline-formula><tex-math notation="LaTeX">${\text{mm}}^2$</tex-math></inline-formula>.
Prevalence and Genetic Diversity of Toxoplasma gondii in Free-Ranging Chickens from the Caribbean

Toxoplasma gondii is a zoonotic parasite capable of infecting a wide range of hosts. Free-range chickens are important sentinels in the epidemiology of this parasite as they feed from the ground and are likely to ingest oocysts shed in the faeces of infected cats. Atypical strains of T. gondii are known to dominate in South America where they are associated with more severe disease in humans, yet relatively little is known about the strains circulating in neighbouring Caribbean islands. In this study, hearts and brains were collected from free-range chickens in Antigua and Barbuda (n = 45), Dominica (n = 76) and Trinidad (n = 41), and DNA was extracted for nested ITS1 PCR and PCR–RFLP. Sera were collected and screened for antibodies using the modified agglutination test (MAT). Antibodies to T. gondii were detected in 20.5, 38.2 and 17.1% of chickens in Antigua and Barbuda, Dominica and Trinidad, respectively. Toxoplasma gondii DNA was also detected by PCR in 24.4, 17.1 and 17.1% of chickens, respectively, giving an overall prevalence of 31.1, 42.1, and 29.3% for each of the 3 island nations. Results of PCR–RFLP revealed 2 new atypical genotypes (designated ToxoDB #281 and #282) and one Type III (ToxoDB #2) in chickens from Antigua. Partial genotyping of a further 8 isolates (7 from Antigua and one from Trinidad) revealed different allele-types at five or more markers for 7 of the isolates, suggesting atypical genotypes. This is the first study to report the prevalence of T. gondii in free-range chickens in Antigua and Barbuda, Dominica and Trinidad and Tobago. It is also the first to report the presence of atypical genotypes in Antigua and Barbuda and Trinidad and Tobago.
Cardiac myosin activation with 2-deoxy-ATP via increased electrostatic interactions with actin

Significance The development of several small-molecule myosin activators to rescue cardiac contractility of failing hearts is underway, but understanding the multiscale structure-function consequences of these inotropes remains a major challenge. Using 2′-deoxy-adenosine 5′-triphosphate (dATP; a myosin-binding nucleotide) as a molecular probe, we show that a restructuring of prepowerstroke myosin in the presence of 2-deoxy-adenosine 5′-diphosphate and inorganic phosphate (dADP.Pi) (versus ADP.Pi) increases actin–myosin electrostatic interactions and binding kinetics. X-ray diffraction revealed myosin structure with dATP in relaxed myofilament is similar to the activated state with ATP, with S1 head movement toward actin and stabilization, resulting in an improved probability of strong cross-bridge formation upon activation. Thus, the alterations induced by dATP may provide clues to a more optimal structure of cardiac myosin to be attained by myosin-targeted therapies for heart failure. The naturally occurring nucleotide 2-deoxy-adenosine 5′-triphosphate (dATP) can be used by cardiac muscle as an alternative energy substrate for myosin chemomechanical activity. We and others have previously shown that dATP increases contractile force in normal hearts and models of depressed systolic function, but the structural basis of these effects has remained unresolved. In this work, we combine multiple techniques to provide structural and functional information at the angstrom-nanometer and millisecond time scales, demonstrating the ability to make both structural measurements and quantitative kinetic estimates of weak actin–myosin interactions that underpin sarcomere dynamics. Exploiting dATP as a molecular probe, we assess how small changes in myosin structure translate to electrostatic-based changes in sarcomere function to augment contractility in cardiac muscle. Through Brownian dynamics simulation and computational structural analysis, we found that deoxy-hydrolysis products [2-deoxy-adenosine 5′-diphosphate (dADP) and inorganic phosphate (Pi)] bound to prepowerstroke myosin induce an allosteric restructuring of the actin-binding surface on myosin to increase the rate of cross-bridge formation. We then show experimentally that this predicted effect translates into increased electrostatic interactions between actin and cardiac myosin in vitro. Finally, using small-angle X-ray diffraction analysis of sarcomere structure, we demonstrate that the proposed increased electrostatic affinity of myosin for actin causes a disruption of the resting conformation of myosin motors, resulting in their repositioning toward the thin filament before activation. The dATP-mediated structural alterations in myosin reported here may provide insight into an improved criterion for the design or selection of small molecules to be developed as therapeutic agents to treat systolic dysfunction.
Expression of WD Repeat Domain 5 (WDR5) is Associated with Progression and Reduced Prognosis in Papillary Thyroid Carcinoma

Background The WD repeat domain 5 (WDR5) is an essential component of methyltransferase complexes. The expression of WDR5 has been reported in several types of malignancy. This study aimed to investigate the expression of the WDR5 gene and protein in a human papillary carcinoma cell line in vitro, including the use WDR5 gene silencing, and the expression of the WDR5 protein in papillary thyroid carcinoma tissue, and clinicopathological characteristics including overall survival (OS). Material/Methods The role of WDR5 in proliferation and migration of the human papillary thyroid carcinoma cell line, KTC-1, was investigated using the cell counting kit-8 (CCK-8) assay and transwell assay after silencing WDR5 expression. Expression levels of WDR5 in 84 patients with papillary thyroid carcinoma were detected using immunohistochemistry. The correlation between WDR5 expression and clinicopathological features was analyzed using the chi-squared test. The prognostic role of WDR5 was evaluated by univariate analysis with the log-rank test, and by multivariate analysis with the Cox regression model. Results WDR5 expression promoted the proliferation and migration of the KTC-1 cells. In tumor tissue from patients with papillary thyroid carcinoma, low expression and high expression levels of WDR5 were found in 72.6% and 27.4%, respectively. Increased expression of WDR5 was significantly associated with lymphatic invasion and reduced survival rates. WDR5 expression was an independent negative prognostic biomarker. Conclusions Expression of WDR5 promoted cell proliferation and migration in vitro and was associated with reduced prognosis in patients with papillary thyroid carcinoma.
Accurate quantification of right ventricular mass at MR imaging by using cine true fast imaging with steady-state precession: study in dogs.

PURPOSE To assess the accuracy of cine magnetic resonance (MR) imaging with a segmented true fast imaging with steady-state precession (FISP) technique for right ventricular (RV) mass quantification. MATERIALS AND METHODS Fourteen dogs were imaged with a 1.5-T clinical MR imaging unit by using an electrocardiographically gated true FISP sequence. Contiguous segmented k-space cine images were acquired from the base of the RV to the apex during suspended respiration (repetition time msec/echo time msec, 3.2/1.6; section thickness, 5 mm; in-plane resolution, 1.0 x 1.3 mm2). After imaging, each dog was sacrificed, and the RV free wall was isolated and weighed. Each MR imaging data set was analyzed twice by each of two independent observers who were blinded to the results of RV mass measurement at autopsy, and the mass measurements at MR imaging were compared with the autopsy results by using linear regression and Bland-Altman analysis. RESULTS RV mass measurements calculated by using the true FISP cine MR images were nearly identical to those at autopsy (R = 0.82, standard error of the estimate = 1.7 g, P >.05), with a mean difference between the autopsy and MR imaging measurements of 0.3 g +/- 1.7 (1.9% +/- 8.2) (P >.05). Inter- and intraobserver variations were small, with a mean interobserver variability of -0.1 g +/- 2.3 and a mean intraobserver variability of 0.2 g +/- 1.6 at every-section analysis. CONCLUSION In this animal model, true FISP cine MR imaging enabled accurate quantification of RV mass.
What and How the Deaf Brain Sees

Over the past decade, there has been an unprecedented level of interest and progress into understanding visual processing in the brain of the deaf. Specifically, when the brain is deprived of input from one sensory modality (such as hearing), it often compensates with supranormal performance in one or more of the intact sensory systems (such as vision). Recent psychophysical, functional imaging, and reversible deactivation studies have converged to define the specific visual abilities that are enhanced in the deaf, as well as the cortical loci that undergo crossmodal plasticity in the deaf and are responsible for mediating these superior visual functions. Examination of these investigations reveals that central visual functions, such as object and facial discrimination, and peripheral visual functions, such as motion detection, visual localization, visuomotor synchronization, and Vernier acuity (measured in the periphery), are specifically enhanced in the deaf, compared with hearing participants. Furthermore, the cortical loci identified to mediate these functions reside in deaf auditory cortex: BA 41, BA 42, and BA 22, in addition to the rostral area, planum temporale, Te3, and temporal voice area in humans; primary auditory cortex, anterior auditory field, dorsal zone of auditory cortex, auditory field of the anterior ectosylvian sulcus, and posterior auditory field in cats; and primary auditory cortex and anterior auditory field in both ferrets and mice. Overall, the findings from these studies show that crossmodal reorganization in auditory cortex of the deaf is responsible for the superior visual abilities of the deaf.