Miracle-dz/UniFAR-FTUs huggingface dataset:
Proliferative Index in Invasive Tumor Front of Oral Squamous Cell Carcinoma: A Potential Prognostic Indicator.

AIM The aim of the study was to evaluate the proliferative index (PI) at their invasive front of oral cancer and their association with Bryne's grades of oral squamous cell carcinoma (OSCC) and compare the PI with lymph node metastasis, site of involvement, and habits. MATERIALS AND METHODS The Ki-67 antigen expression was immunohistochemically evaluated in a total of 102 cases that included the histopathologically diagnosed archival specimens of OSCCs. They were subdivided by Bryne's histopathological grading into grade I (40 cases), grade II (32 cases), and grade III (30 cases). The nucleus with brown stain was considered positive. Cells were counted under 400× magnification. The proliferative activity thus determined was then expressed as a percentage of Ki-67 labeling index (Ki-67 LI) positive cells. RESULTS A stepwise increase in the mean Ki-67 LI was found from grade I to III squamous cell carcinoma, thus correlating with the histological grading. In addition, there was a higher PI seen in cases associated with metastatic lymph node, which concords with the higher biologic aggressiveness and poor prognosis of the lesion. CONCLUSION The present study shows a definitive correlation of Ki-67 antigen with the Bryne's histological grading, all the parameters of Bryne's grading for OSCC and lymph node status of the patient proving its association as an effective tool to grade the tumors and finally read the prognosis of the tumor. CLINICAL SIGNIFICANCE Cell proliferation is regarded as one of the most important biologic mechanisms in oncogenesis. The role of cell proliferation in tumor progression has been inferred in studies concerned with human cancer by comparing the PI of normal tissue, preneoplastic and neoplastic lesions. The Ki-67 antigen-labeled cells can prove to be an effective aid to grade the tumors. It might be possible to standardize and objectify tumor grading among pathology laboratories.
Cultural Adaptation of a Quality-of-Life Measure for Urinary Incontinence

Objectives: To translate and validate a urinary incontinence-specific measure of quality of life (I-QOL) in French, Spanish, Swedish, and German and provide translations only into seven other languages and variants of these languages. Methods: Quality of life and linguistic experts prepared two forward translations from American English to their native languages and helped to harmonize these translations at a meeting. In the four European countries, the adapted versions of the I-QOL were administered to 259 women with stress, urge, and mixed incontinence. Principal component analyses were used to confirm the proposed measurement model suggested by patient interviews. Psychometric testing was conducted using standardized procedures. Results: Translation procedures resulted in a change in the original instrument’s Likert response scale from 4 to 5 points. Principal component analyses confirmed three patient-derived subscales and higher-order factor analysis confirmed a total summary score. In all countries, the internal consistency (alpha) and reproducibility (ICC) were high (alpha ranged between 0.87 and 0.93); (ICC ranged between 0.92 and 0.95). In all countries, I-QOL scores were significantly worse (p < 0.001) as perceived severity of incontinence, use of services, and number of incontinent episodes increased. Conclusions: The I-QOL has been adapted successfully into eleven languages and six variants of these languages. The cross-sectional psychometric properties of the US version were confirmed in four European countries. The I-QOL fills the need for a valid, international quality-of-life instrument for incorporation in clinical trials covering patients with varying types and severity of urinary incontinence.
Assessing the effect of D-xylose on the sugar signaling pathways of Saccharomyces cerevisiae in strains engineered for xylose transport and assimilation

One of the challenges of establishing an industrially competitive process to ferment lignocellulose to value-added products using Saccharomyces cerevisiae is to get efficient mixed sugar fermentations. Despite successful metabolic engineering strategies, the xylose assimilation rates of recombinant S. cerevisiae remain significantly lower than for the preferred carbon source, glucose. Previously, we established a panel of in vivo biosensor strains (TMB371X) where different promoters (HXT1/2/4p; SUC2p, CAT8p; TPS1p/2p, TEF4p) from the main sugar signaling pathways were coupled with the yEGFP3 gene, and observed that wild-type S. cerevisiae cannot sense extracellular xylose. Here, we expand upon these strains by adding a mutated galactose transporter (GAL2-N376F) with improved xylose affinity (TMB372X), and both the transporter and an oxidoreductase xylose pathway (TMB375X). On xylose, the TMB372X strains displayed population heterogeneities, which disappeared when carbon starvation was relieved by the addition of the xylose assimilation pathway (TMB375X). Furthermore, the signal in the TMB375X strains on high xylose (50 g/L) was very similar to the signal recorded on low glucose (≤5 g/L). This suggests that intracellular xylose triggers a similar signal to carbon limitation in cells that are actively metabolizing xylose, in turn causing the low assimilation rates.
Adolescent Alcohol, Tobacco, and Marijuana Use: The Influence of Neighborhood Disorder and Hope

Purpose. To investigate relationships between adolescents' current alcohol, tobacco, and marijuana use; perceptions of neighborhood disorder; and sense of hope. Design. Questionnaires were administered to a nonrandom sample of middle school students during the spring of 1999. Subjects. The ethnically and geographically diverse sample (n = 369), from a range of low socioeconomic status backgrounds, was considered to be at high risk for alcohol, tobacco, and other drug use because of previous enrollment in low socioeconomic status elementary schools. Measures. Alcohol, tobacco, and marijuana use were dichotomized into current and never/no use. Six variables described neighborhood social disorder. Sense of hope was assessed using the Children's Hope Scale. Results. Statistically significant relationships were found between perceived neighborhood disorder and current alcohol (p = .01), tobacco (p = .001), and marijuana (p < .001) use. A statistically significant and independent relationship was found between sense of hope and current alcohol (p = .02), tobacco (p = .02), and marijuana (p = .06) use. Results indicated linear trends in participants' increased use of alcohol, tobacco, and marijuana and (1) perception of higher neighborhood disorder and (2) lower sense of hope. Conclusion. Substance use prevention programs for youth might usefully be directed not only to agdolescents but also to the neighborhoods in which they live. Additionally, it would be important to emphasize creating safer neighborhood environments that support the development of a stronger sense of hope for the future.
Patch-Clamp-Induced Perturbations of [Ca2+]i Activity in Somatotropes

Somatotropes and GC cells, a GH-producing cell line, exhibit [Ca<sup>2+</sup>]<sub>i</sub> oscillations that result from rhythmic Ca<sup>2+</sup> action potentials. Determination of this operating mode required simultaneous recording of both parameters by fura-2 imaging and patch-clamp techniques. In order to test whether patch recording induces artificial alteration of the [Ca<sup>2+</sup>]<sub>i</sub> oscillatory pattern, we recorded separately or simultaneously [Ca<sup>2+</sup>]<sub>i</sub> and membrane potential. In the absence of any other stimulation, seal formation in patch-clamp recording evoked by itself a 2.5- to 4-fold persistent increase in basal [Ca<sup>2+</sup>]<sub>i</sub>, speeded up their frequency (from 0.03–0.17 to 0.4 Hz) and changed their pattern to a tonic mode. Patch-induced [Ca<sup>2+</sup>]<sub>i</sub> increase was reproduced by mechanical contact between the pipette and the membrane. It was reduced by nifedipine, a blocker of L-type Ca<sup>2+</sup> channels, as well as by removal of external Na<sup>+</sup>. It was fully blocked by external Ca<sup>2+</sup> removal or gadolinium. All patch-clamp-induced perturbations were reversed by membrane hyperpolarization. We propose that patch-clamp recording evokes Ca<sup>2+</sup> entry through L-type Ca<sup>2+</sup> channels either directly, or indirectly via membrane depolarization. This shows that patch recordings in endocrine cells showing mechanosensitivity have to be interpreted with caution, and explains why long-lasting patch recordings are so difficult to obtain.
REM Sleep Behavior Disorder in Parkinson's Disease and Other Synucleinopathies

Rapid eye movement sleep behavior disorder is characterized by dream enactment and complex motor behaviors during rapid eye movement sleep and rapid eye movement sleep atonia loss (rapid eye movement sleep without atonia) during polysomnography. Rapid eye movement sleep behavior disorder may be idiopathic or symptomatic and in both settings is highly associated with synucleinopathy neurodegeneration, especially Parkinson's disease, dementia with Lewy bodies, multiple system atrophy, and pure autonomic failure. Rapid eye movement sleep behavior disorder frequently manifests years to decades prior to overt motor, cognitive, or autonomic impairments as the presenting manifestation of synucleinopathy, along with other subtler prodromal “soft” signs of hyposmia, constipation, and orthostatic hypotension. Between 35% and 91.9% of patients initially diagnosed with idiopathic rapid eye movement sleep behavior disorder at a sleep center later develop a defined neurodegenerative disease. Less is known about the long‐term prognosis of community‐dwelling younger patients, especially women, and rapid eye movement sleep behavior disorder associated with antidepressant medications. Patients with rapid eye movement sleep behavior disorder are frequently prone to sleep‐related injuries and should be treated to prevent injury with either melatonin 3‐12 mg or clonazepam 0.5‐2.0 mg to limit injury potential. Further evidence‐based studies about rapid eye movement sleep behavior disorder are greatly needed, both to enable accurate prognostic prediction of end synucleinopathy phenotypes for individual patients and to support the application of symptomatic and neuroprotective therapies. Rapid eye movement sleep behavior disorder as a prodromal synucleinopathy represents a defined time point at which neuroprotective therapies could potentially be applied for the prevention of Parkinson's disease, dementia with Lewy bodies, multiple system atrophy, and pure autonomic failure. © 2017 International Parkinson and Movement Disorder Society
Adjuvant Transarterial Chemoembolization for HBV-Related Hepatocellular Carcinoma After Resection: A Randomized Controlled Study

Purpose: The survival of patients with hepatocellular carcinoma (HCC) recurrence after curative resection is usually poor. We sought to evaluate the safety and efficacy of adjuvant transarterial chemoembolization (TACE) in HBV-related HCC patients with an intermediate (a single tumor larger than 5 cm without microvascular invasion) or high risk (a single tumor with microvascular invasion, or two or three tumors) of recurrence. Experimental Design: In this randomized phase 3 trial, 280 eligible patients were assigned to adjuvant TACE (n = 140) or no adjuvant treatment (control; n = 140) groups. The primary endpoint was recurrence-free survival (RFS); secondary endpoints included overall survival (OS) and safety. Multivariable Cox-proportional hazards model was used to determine the independent impact of TACE on patients' outcomes. Results: Patients who received adjuvant TACE had a significantly longer RFS than those in the control group [56.0% vs. 42.1%, P = 0.01; HR, 0.68; 95% confidence interval (CI), 0.49–0.93]. Patients in the adjuvant TACE group had 7.8% higher 3-year OS rate than the control group (85.2% vs. 77.4%; P = 0.04; HR, 0.59; 95% CI, 0.36–0.97). The impact of adjuvant TACE on RFS and OS remained significant after controlling for other known prognostic factors (HR, 0.67; P = 0.01 for RFS; and HR, 0.59; P = 0.04 for OS). There was no grade 3 or 4 toxicity after adjuvant TACE. Conclusions: For patients with HBV-related HCC who had an intermediate or high risk of recurrence after curative hepatectomy, our study showed adjuvant TACE significantly reduced tumor recurrence, improved RFS and OS, and the procedure was well tolerated. Clin Cancer Res; 24(9); 2074–81. ©2018 AACR.
Cellular plasticity in cardiovascular development and disease

Knowledge on cellular differentiation pathways is critical to understanding organ development, homeostasis, and disease. Studying cell differentiation and cell fate restrictions in these contexts can be done through lineage tracing experiments, which entail permanent labeling of a cell and all its progeny. Recent lineage experiments within the cardiovascular system have uncovered unexpected findings on cellular origins during organogenesis and cell plasticity during disease. For example, there is increasing evidence that multiple progenitor sources exist for a single cell type, and that cells have remarkable expansive capacities under disease settings. Here, we summarize some recent findings in the cardiovascular system and highlight where there is evidence that the underlying concepts are a widespread phenomenon used by other organ systems. Developmental Dynamics 246:328–335, 2017. © 2016 Wiley Periodicals, Inc.
Inconsistent Condom Use Among Male University Students in Northern Thailand

University students are at increased risk of HIV infection, but little is known about the determinants of inconsistent condom use among them. The study aims to assess the association of sociodemographic, individual, dyadic, and social factors with inconsistent condom use among male university students. Of 1091 participants, 67.0% had sexual intercourse, though 64.4% had inconsistent condom use. It was found that “did not use a condom at first sexual intercourse” (adjusted odds ratio [AOR] 6.1; CI, 3.7-10.1), “history of STIs” (AOR, 2.1; CI, 1.0-4.2), low “self-efficacy” (AOR, 2.4; CI, 1.3-4.7), “perception that condom use reduces pleasure” (AOR, 1.4; CI, 1.0-2.1), and “high subjective norm” (AOR, 1.9; CI, 1.3-2.8) were associated with increased odds of inconsistent condom use. Condom use should be promoted from the onset of sexual activity to establish a habit of safe sex practices and for improvement in self-efficacy of condom use. Emphasis must be laid on pleasure-enhancing benefits of condom use and changing social norms.
Sexual Dimorphisms in the Brainstem of the Green Anole Lizard

Male green anoles (Anolis carolinensis) court females by extending a bright red throat fan, called a dewlap. The dewlap is larger in males than in females who do not display the structure in the context of courtship. The ceratohyoid muscle and second ceratobranchial cartilage which control dewlap extension are significantly larger in male than in female anoles. Neurons innervating the ceratohyoid muscle were retrogradely labeled by injecting the muscle with fast blue and were found to be located in the vagal portion of nucleus ambiguus (Amb X), as well as in the region containing the glossopharyngeal portion of nucleus ambiguus (Amb IX) and the ventral portion of the motor nucleus of the facial nerve (nVIImv). Cells in both areas were larger in males than in females. These parallels between structure and function provide the opportunity to study mechanisms of sexual differentiation of brain and behavior.
Virulence characteristics and phylogenetic background of multidrug-resistant and antimicrobial-susceptible clinical isolates of Escherichia coli from across the United States, 2000-2001.

BACKGROUND Increases in antimicrobial resistance in Escherichia coli have been paralleled by an increasing incidence of E. coli sepsis, suggesting a possible link between resistance and virulence. METHODS All 76 multidrug-resistant (MDR) E. coli isolates (i.e., those resistant to > or =3 antimicrobial agents, including ampicillin, ceftazidime, trimethoprim-sulfamethoxazole, gentamicin, and ciprofloxacin) reported to the Tracking Resistance in the United States Today studies during 2000-2001 and 76 closely matched pansusceptible control isolates were studied. Extended virulence profiles and E. coli phylogenetic group (A, B1, B2, or D) were compared between groups. RESULTS The MDR isolates, which represented predominantly non-B2 phylogenetic groups (91%), exhibited significantly reduced molecular virulence, compared with the predominantly group B2-derived control isolates (58%). Only 30% of MDR isolates, compared with 61% of control isolates (P<.001), qualified as extraintestinal pathogenic E. coli (ExPEC), and even these isolates exhibited significantly lower virulence scores than did susceptible ExPEC (7.25 vs. 9.0; P=.001). Phylogenetic differences accounted for the apparent virulence differences between MDR and control isolates. CONCLUSIONS These findings argue against a direct link between virulence traits and antimicrobial resistance in E. coli. Instead, they call into question why non-B2 strains are more commonly MDR, with differential exposure to selection pressure (including in agriculture) as one possible explanation.
Microglia in Alzheimer’s disease

Proliferation and activation of microglia in the brain, concentrated around amyloid plaques, is a prominent feature of Alzheimer’s disease (AD). Human genetics data point to a key role for microglia in the pathogenesis of AD. The majority of risk genes for AD are highly expressed (and many are selectively expressed) by microglia in the brain. There is mounting evidence that microglia protect against the incidence of AD, as impaired microglial activities and altered microglial responses to &bgr;-amyloid are associated with increased AD risk. On the other hand, there is also abundant evidence that activated microglia can be harmful to neurons. Microglia can mediate synapse loss by engulfment of synapses, likely via a complement-dependent mechanism; they can also exacerbate tau pathology and secrete inflammatory factors that can injure neurons directly or via activation of neurotoxic astrocytes. Gene expression profiles indicate multiple states of microglial activation in neurodegenerative disease settings, which might explain the disparate roles of microglia in the development and progression of AD pathology.
An experimental comparative study of the efficiency of twisted and flat flapping wings during hovering flight

This work presents a parametric study to find a proper wing configuration for achieving economical flight using unsteady blade element theory, which is based on the 3D kinematics of a flapping wing. Power loading was first considered as a performance parameter for the study. The power loadings at each wing section along the wingspan were obtained for various geometric angles of attack (AoAs) by calculating the ratios of the vertical forces generated and the power consumed by that particular wing section. The results revealed that the power loading of a negatively twisted wing could be higher than the power loading that a flat wing can have; the power loading of the negatively twisted wing was approximately 5.9% higher. Given the relatively low average geometric AoA (αA,root ≈ 44° and αA,tip ≈ 25°), the vertical force produced by the twisted wing for the highest power loading was approximately 24.4% less than that produced by the twisted wing for the strongest vertical force. Therefore, for a given wing geometry and flapping amplitude, a flapping-wing micro air vehicle required a 13.5% increase in flapping frequency to generate the same strongest cycle-average vertical force while saving about 24.3% power. However, when force3/power2 and force2/power ratios were considered as performance indices, the twisted wings for the highest force3/power2 (αA,root ≈ 43° and αA,tip ≈ 30°) and force2/power (αA,root ≈ 43° and αA,tip ≈ 36°) required only 6.5% and 4% increases in flapping frequency and consumed 26.2% and 25.3% less power, respectively. Thus, it is preferable to use a flapping wing operating at a high frequency using the geometric AoAs for the highest power loading, force3/power2 ratio, and force2/power ratio over a flapping wing operating at a low frequency using a high geometric AoA with the strongest vertical force. Additionally, by considering both aerodynamic and inertial forces, this study obtained average geometric AoAs in the range of 30° to 40°, which are similar to those of a typical hovering insect’s wings. Therefore, the operation of an aerodynamically uneconomical, high AoA in a hovering insect’s wings during flight is explainable.
Implementation of the Autovalidation Algorithm for Clinical Chemistry Testing in the Laboratory Information System

Objective Autovalidation algorithm should be properly designed with clearly defined criteria and any data that do not meet the criteria, must be reviewed and manually validated. The aim was to define the rules for autovalidation in our laboratory information system (LIS), and validate the algorithm prior to its implementation in routine laboratory work. Methods Autovalidation was implemented for all routine serum biochemistry tests. The algorithm included analytical measurement ranges (AMR), delta check, critical values, serum indices and all preanalytical and analytical flags from the analyzer. Results In the validation process 9805 samples were included, and 78.3% (7677) of all samples were autovalidated. The highest percentage of non-validated samples (54.9%) refers to those with at least one result outside the method linearity ranges (AMR criteria) while critical values were observed to be the least frequent criterion for stopping autovalidation (1.8%). Also, 38 samples were manually validated as they failed to meet the autovalidation criteria. Conclusion Implementation of algorithm for autovalidation in our institution resulted in the redesign of the existing LIS. This model of the autovalidation algorithm significantly decreased the number of manually validated test results and can be used as a model for introducing autovalidation in other laboratory settings.
Regulation of circulating chromogranin B levels in heart failure

Abstract Background: Chromogranin B (CGB) regulates B-type natriuretic peptide (BNP) production. Circulating CGB levels are elevated in heart failure (HF) animal models and HF patients, but also increase in healthy individuals in response to physical activity. Therefore, CGB seems to integrate information from myocardial stress and systemic neuro-endocrine activation. Substantial gaps remain in our understanding of CGB regulation in HF. Methods and results: We conducted a retrospective registry study including 372 patients. CGB and N-terminal pro-BNP (NT-proBNP) plasma levels were assessed in acute HF and chronic valvular HF patients and controls. CGB levels were significantly increased in acute HF and chronic valvular HF, but significantly higher in the latter. Patients in chronic valvular HF with severe mitral regurgitation (cHF-MR) showed significantly higher CGB levels than patients in chronic valvular HF with severe aortic stenosis. CGB levels progressively increased with worsening NYHA functional status and were moderately correlated to NT-proBNP, but independent of left ventricular (LV) ejection fraction (LVEF), LV mass, age and body weight. Finally, cHF-MR patients showed significant reductions of CGB levels after interventional mitral valve repair. Conclusion: CGB is a promising emerging biomarker in HF patients with unique potential to integrate information from myocardial stress and neuro-endocrine activation.