Miracle-dz/UniFAR-FTUs huggingface dataset:
Clinical and Laboratory Investigations The time from diagnostic excision biopsy to wide local excision for primary cutaneous malignant melanoma may not affect patient survival

Background The surgical management of primary cutaneous malignant melanoma usually involves an excision biopsy of the suspected lesion followed by wide local excision. No study has addressed whether a delay between these two surgical procedures influences patient outcome. Objectives To determine if the surgical interval (SI) between the diagnostic excision biopsy and wide local excision for primary cutaneous malignant melanoma affects recurrence or survival outcome. Methods A cohort of 986 patients who had a diagnostic excision biopsy followed by wide local excision was identified from those registered on a specialist database that records the clinicopathological features, surgical treatment and follow-up information of all patients with malignant melanoma in Scotland. The cohort was divided into five arbitrary groups determined by the length of the SI as follows: £ 14 days, 15–28 days, 29–42 days, 43–91 days and ‡92 days. Overall survival, disease-free survival and recurrence-free interval between the groups were compared univariately and multivariately. Results The mean age at excision biopsy was 47Æ4 years and the median period of follow-up was 5 years (range 27 days to 20Æ7 years). The median SI was 30 days (range 1–468 days). The SI was: (i) £ 14 days for 130 (13%); (ii) 15–28 days for 320 (33%); (iii) 29–42 days for 262 (27%); (iv) 43–91 days for 251 (25%); and (v) ‡92 days for 23 (2%) patients. The latter group was older, had thinner melanomas, a higher percentage of lesions on the head and neck, fewer superficial spreading malignant melanomas and ulceration present less often compared with patients treated earlier. Univariately, there was no significant difference in overall survival (P 1⁄4 0Æ60) or diseasefree survival (P 1⁄4 0Æ24) between the groups. Although there was a statistically significant difference in the percentage of recurrence-free patients between the groups (P 1⁄4 0Æ011), the better recurrence-free rates occurred in the 29–42 and 43–91 day groups. After adjusting for age, sex, tumour thickness, site, histology, ulceration and mitotic activity using Cox’s proportional hazards model, there was no statistically significant difference in overall survival, disease-free survival and recurrence-free percentages between the surgical groups (P 1⁄4 0Æ88, P 1⁄4 0Æ44 and P 1⁄4 0Æ084, respectively). Conclusions There was no evidence that survival outcome or recurrence was related to the time interval between the diagnostic excision biopsy and wide local excision of melanoma.
Combined moist airtight storage and feed fermentation of barley by the yeast Wickerhamomyces anomalus and a lactic acid bacteria consortium

This study combined moist airtight storage of moist grain with pig feed fermentation. Starter cultures with the potential to facilitate both technologies were added to airtight stored moist crimped cereal grain, and the impact on storage microflora and the quality of feed fermentations generated from the grain was investigated. Four treatments were compared: three based on moist barley, either un-inoculated (M), inoculated with Wickerhamomyces anomalus (W), or inoculated with W. anomalus and LAB starter culture, containing Pediococcus acidilactici DSM 16243, Pediococcus pentosaceus DSM 12834 and Lactobacillus plantarum DSM 12837 (WLAB); and one treatment based on dried barley (D). After 6 weeks of storage, four feed fermentations FM, FW, FWLAB, and FD, were initiated from M, W, WLAB, and D, respectively, by mixing the grain with water to a dry matter content of 30%. Each treatment was fermented in batch initially for 7 days and then kept in a continuous mode by adding new feed daily with 50% back-slop. During the 6 week storage period, the average water activity decreased in M, W and WLAB from 0.96 to 0.85, and cereal pH decreased from approximately 6.0 at harvest to 4.5. Feed fermentation conferred a further pH decrease to 3.8–4.1. In M, W and WLAB, molds and Enterobacteriaceae were mostly below detection limit, whereas both organism groups were detected in D. In fermented feed, Enterobacteriaceae were below detection limit in almost all conditions. Molds were detected in FD, for most of the fermentation time in FM and at some sampling points in FW and FWLAB. Starter organisms, especially W. anomalus and L. plantarum comprised a considerable proportion of the yeast and LAB populations, respectively, in both stored grain and fermented feed. However, autochthonous Pichia kudriavzevii and Kazachstania exigua partially dominated the yeast populations in stored grain and fermented feed, respectively.
Duck Hepatitis A Virus Possesses a Distinct Type IV Internal Ribosome Entry Site Element of Picornavirus

ABSTRACT Sequence analysis of duck hepatitis virus type 1 (DHV-1) led to its classification as the only member of a new genus, Avihepatovirus, of the family Picornaviridae, and so was renamed duck hepatitis A virus (DHAV). The 5′ untranslated region (5′ UTR) plays an important role in translation initiation and RNA synthesis of the picornavirus. Here, we provide evidence that the 651-nucleotide (nt)-long 5′ UTR of DHAV genome contains an internal ribosome entry site (IRES) element that functions efficiently in vitro and within BHK cells. Comparative sequence analysis showed that the 3′ part of the DHAV 5′ UTR is similar to the porcine teschovirus 1 (PTV-1) IRES in sequence and predicted secondary structure. Further mutational analyses of the predicted domain IIId, domain IIIe, and pseudoknot structure at the 3′ end of the DHAV IRES support our predicted secondary structure. However, unlike the case for the PTV-1 IRES element, analysis of various deletion mutants demonstrated that the optimally functional DHAV IRES element with a size of approximately 420 nt is larger than that of PTV-1 and contains other peripheral domains (Id and Ie) that do not exist within the type IV IRES elements. The domain Ie, however, could be removed without significant loss of activity. Surprisingly, like the hepatitis A virus (HAV) IRES element, the activity of DHAV IRES could be eliminated by expression of enterovirus 2A protease. These findings indicate that the DHAV IRES shares common features with type IV picornavirus IRES elements, whereas it exhibits significant differences from type IV IRESs. Therefore, we propose that DHAV possesses a distinct type IV IRES element of picornavirus.
EGFR gene copy number as a predictive biomarker for patients receiving tyrosine kinase inhibitor treatment: a systematic review and meta-analysis in non-small-cell lung cancer.

INTRODUCTION We conducted a systematic review and meta-analysis to assess epidermal growth factor receptor (EGFR) gene copy number as a potential biomarker of survival for patients with advanced non-small-cell lung cancer (NSCLC) receiving single-agent treatment with EGFR tyrosine kinase inhibitors (TKIs). METHODS We systematically identified articles investigating EGFR gene copy number by fluorescent or chromogenic in situ hybridization in patients with advanced or recurrent NSCLC treated with the TKIs erlotinib or gefitinib, (last search: 31 June 2009). Eligible studies had to report on overall survival (OS), progression-free survival (PFS) or time-to-progression (TTP), stratified by EGFR gene copy number. Summary hazard ratios (HRs) were calculated using random-effects models. RESULTS Among 255 identified studies, 20 (1689 patients, 594 with increased gene copy number), 10 (822 patients, 290 with increased gene copy number) and 5 (294 patients, 129 with increased gene copy number) were eligible for the OS, PFS and TTP meta-analyses, respectively. Increased EGFR gene copy number was associated with increased OS (HR = 0.77; 95% CI 0.66-0.89; P = 0.001), PFS (HR = 0.60; 95% CI 0.46-0.79; P<0.001) and TTP (HR = 0.50; 95% CI 0.28-0.91; P = 0.02). Among predominantly white populations, increased EGFR gene copy number was strongly associated with improved survival (HR = 0.70; 95% CI 0.59-0.82; P<0.001), whereas it did not influence survival in East Asians (HR = 1.11; 95% CI 0.82-1.50; P=0.50). This difference was statistically significant (P=0.02). CONCLUSION Among TKI-treated patients, increased EGFR gene copy number appears to be associated with improved survival outcomes. The effect on OS appears to be limited to patients of non-Asian descent.
KCNQ Potassium Channels Modulate Sensitivity of Skin Down-hair (D-hair) Mechanoreceptors*

M-current-mediating KCNQ (Kv7) channels play an important role in regulating the excitability of neuronal cells, as highlighted by mutations in Kcnq2 and Kcnq3 that underlie certain forms of epilepsy. In addition to their expression in brain, KCNQ2 and -3 are also found in the somatosensory system. We have now detected both KCNQ2 and KCNQ3 in a subset of dorsal root ganglia neurons that correspond to D-hair Aδ-fibers and demonstrate KCNQ3 expression in peripheral nerve endings of cutaneous D-hair follicles. Electrophysiological recordings from single D-hair afferents from Kcnq3−/− mice showed increased firing frequencies in response to mechanical ramp-and-hold stimuli. This effect was particularly pronounced at slow indentation velocities. Additional reduction of KCNQ2 expression further increased D-hair sensitivity. Together with previous work on the specific role of KCNQ4 in rapidly adapting skin mechanoreceptors, our results show that different KCNQ isoforms are specifically expressed in particular subsets of mechanosensory neurons and modulate their sensitivity directly in sensory nerve endings.
Hepatitis B Virus Subgenotype A1: Evolutionary Relationships between Brazilian, African and Asian Isolates

Brazil is a country of low hepatitis B virus (HBV) endemicity in which the genotype A of HBV (HBV/A) is the most prevalent. The complete nucleotide sequences of 26 HBV/A isolates, originating from eight Brazilian states, were determined. All were adw2. Twenty-three belonged to subgenotype A1 and three to A2. By phylogenetic analysis, it was shown that all the 23 HBV/A1 isolates clustered together with isolates from Bangladesh, India, Japan, Nepal, the Philippines and United Arab Emirates, but not with those of Congo, Kenya, Malawi, Rwanda, South Africa, Tanzania, Uganda and Zimbabwe. Four amino acid residues in the polymerase (His138 in the terminal protein domain, Pro18 and His90 in the spacer, and Ser109 in the reverse transcriptase), and one (Phe17) in the precore region, predominated in Latin American and Asian HBV/A1 isolates, but were rarely encountered in African isolates, with the exception of those from Somalia. Specific variations of two adjacent amino acids in the C-terminal domain of the HBx protein, namely Ala146 and Pro147, were found in all the Brazilian, but rarely in the other HBV/A1 isolates. By Bayesian analysis, the existence of an ‘Asian-American’ clade within subgenotype A1 was supported by a posterior probability value of 0.996. The close relatedness of the Brazilian, Asian and Somalian isolates suggests that the HBV/A1 strains predominant in Brazil did not originate from the five million slaves who were imported from Central and Western Africa from 1551 to 1840, but rather from the 300–400,000 captives forcibly removed from southeast Africa at the middle of the 19th century.
Dynamics of individual growth in a recovering population of lake trout (Salvelinus namaycush)

In 1976, the Wisconsin Department of Natural Resources established a refuge for a nearly depleted population of lake trout (Salvelinus namaycush) at Gull Island Shoal, Lake Superior. The refuge was intended to reduce fishing mortality by protecting adult lake trout. We examined the growth dynamics of these lake trout during the period of recovery by comparing estimates of individual growth before and after the refuge was established. Our estimates are based on an annual mark-recapture survey conducted at the spawning area since 1969. We developed a model that allowed mean growth rates to differ among individuals of different sizes and that accommodated variation in growth rates of individuals of the same size. Likelihood ratio tests were used to determine if the mean growth increments of lake trout changed after the refuge was established. Our results suggest that growth of mature lake trout (particularly wild fish) decreased significantly in the postrefuge period. This decreased growth may have been asso.
The value of intraoperative Gram stain in revision total knee arthroplasty.

BACKGROUND The accurate preoperative diagnosis of infection is an essential component of decision-making prior to revision total knee arthroplasty. When preoperative modalities used to detect infection reveal equivocal findings, the surgeon may rely on intraoperative testing. While intraoperative Gram stains are routinely performed during revision total knee arthroplasty, their value remains unclear. METHODS We retrospectively reviewed the records on 945 revision total knee arthroplasties performed at three university institutions to which patients were referred for total joint arthroplasty; the results of an intraoperative Gram stain were available for review in 921 cases (97.5%). Of these knees, 247 were classified as infected on the basis of (1) the presence of the same organism in two cultures; (2) growth, on solid media, of an organism as well as other objective evidence of infection; (3) histologic evidence of acute inflammation; (4) gross purulence; and/or (5) an actively draining sinus. We reviewed the results of preoperative laboratory studies, which included measurements of the erythrocyte sedimentation rate, C-reactive protein values, and white blood-cell count in 90%, 76%, and 98% of cases, respectively. Preoperative aspiration to obtain a specimen for culture and a cell count was performed routinely at one center and selectively at the other two centers, and the results were available for review in 439 (48%) of the 921 cases. RESULTS Intraoperative Gram staining was found to have a sensitivity of 27% and a specificity of 99.9%. The positive and negative predictive values were 98.5% and 79%, respectively. The test accuracy was 80%. Patients with a true-positive Gram stain had a significantly higher preoperative white blood-cell count, C-reactive protein level, and nucleated cell count in the aspirate when compared with patients with a false-negative Gram stain (p < 0.001). In no case did the results of the intraoperative Gram stain alter treatment. CONCLUSIONS The intraoperative Gram stain was found to have poor sensitivity and a poor negative predictive value, and its results did not alter the treatment of any patient undergoing revision total knee arthroplasty because of a suspected infection. These data do not support the routine use of intraoperative Gram staining in revision total knee arthroplasty; instead, they suggest a much more limited role for this test.
A comparison of receptive field and tracer coupling size of horizontal cells in the rabbit retina

Abstract The large receptive fields of retinal horizontal cells are thought to reflect extensive electrical coupling via gap junctions. It was shown recently that the biotinylated tracers, biocytin and Neurobiotin, provide remarkable images of coupling between many types of retinal neuron, including horizontal cells. Further, these demonstrations of tracer coupling between horizontal cells rivaled the size of their receptive fields, suggesting that the pattern of tracer coupling may provide some index of the extent of electrical coupling. We studied this question by comparing the receptive field and tracer coupling size of dark-adapted horizontal cells recorded in the superfused, isolated retina-eyecup of the rabbit. Both the edge-to-edge receptive field and space constants (λ) were computed for each cell using a long, narrow slit of light displaced across the retinal surface. Cells were subsequently labeled by iontophoretic injection of Neurobiotin. The axonless A-type horizontal cells showed extensive, homologous tracer coupling in groups greater than 1000 covering distances averaging about 2 mm. The axon-bearing B-type horizontal cells were less extensively tracer coupled, showing homologous coupling of the somatic endings in groups of about 100 cells spanning approximately 400 μm and a separate homologous coupling of the axon terminal endings covering only about 275 μm. Moreover, we observed a remarkable, linear relationship between the size of the receptive fields of each of the three horizontal cell endings and the magnitude of their tracer coupling. Our findings suggest that the extent of tracer coupling provides a strong, linear index of the magnitude of electrical current flow, as derived from receptive-field measures, across groups of coupled horizontal cells. These data thus provide the first direct evidence that the receptive-field size of horizontal cells is related to the extent of their coupling via gap junctions.
Paired Comparison of Procedural Sequence in Same-day Bidirectional Endoscopy with Moderate Sedation and Carbon Dioxide Insufflation: A Prospective Observational Study

Background/Aims: Same-day bidirectional endoscopy (BDE) is a commonly performed procedure, but the optimal sequence of the procedure with carbon dioxide insufflation is not well established. In this study, we investigated the optimal sequence for same-day BDE without polypectomy under moderate sedation and carbon dioxide insufflation in terms of sedation doses and colonoscopy performance. Patients and Methods: We performed a prospective observational study of 63 asymptomatic patients who were admitted for physical check-ups. A colonoscopy-esophagogastroduodenoscopy (EGD) examination was performed first and then an EGD-colonoscopy examination was performed within 1.5 years. Results: The total procedure time, procedure complexity, bowel preparation quality, cecal intubation time, colon polyp detection rate, and adverse events were similar between the two study groups. The total doses of fentanyl and midazolam were significantly higher for the colonoscopy-EGD group than that for the EGD-colonoscopy group (70.8 ± 9.6 μg vs. 56.6 ± 9.2 μg and 6.1 ± 1.3 mg vs. 4.6 ± 1.1 mg, P < 0.0001 and P < 0.0001, respectively). The recovery time to discharge was significantly longer for the colonoscopy-EGD group compared to the EGD-colonoscopy group (38.5 ± 3.9 min vs. 31.9 ± 3.2 min, P < 0.001, respectively). Conclusions: EGD-colonoscopy is the optimal sequence for same-day BDE. In this order, the procedures are better tolerated, the sedation doses are reduced, and the recovery time is shorter.
Distribution of the anther-smut pathogen Microbotryum on species of the Caryophyllaceae

Summary Understanding disease distributions is of fundamental and applied importance, yet few studies benefit from integrating broad sampling with ecological and phylogenetic data. Here, anther-smut disease, caused by the fungus Microbotryum, was assessed using herbarium specimens of Silene and allied genera of the Caryophyllaceae. A total of 42 000 herbarium specimens were examined, and plant geographical distributions and morphological and life history characteristics were tested as correlates of disease occurrence. Phylogenetic comparative methods were used to determine the association between disease and plant life-span. Disease was found on 391 herbarium specimens from 114 species and all continents with native Silene. Anther smut occurred exclusively on perennial plants, consistent with the pathogen requiring living hosts to overwinter. The disease was estimated to occur in 80% of perennial species of Silene and allied genera. The correlation between plant life-span and disease was highly significant while controlling for the plant phylogeny, but the disease was not correlated with differences in floral morphology. Using resources available in natural history collections, this study illustrates how disease distribution can be determined, not by restriction to a clade of susceptible hosts or to a limited geographical region, but by association with host life-span, a trait that has undergone frequent evolutionary transitions.
When the giant meets the ant an asymmetric approach for collaborative object manipulation

For the 3DUI Contest 2016, we propose an innovative approach that enables two or more users to manipulate an object collaboratively. Our solution is based on an asymmetric collaboration pattern at different scales in which users benefit from suited points of views and interaction techniques according to their device setups. Our system provides an efficient way to co-manipulate an object within irregular and narrow courses, such as the contest material scenes, taking advantages of asymmetric roles in synchronous collaboration.
Low-Dose Curcumin Stimulates Proliferation, Migration and Phagocytic Activity of Olfactory Ensheathing Cells

One of the promising strategies for neural repair therapies is the transplantation of olfactory ensheathing cells (OECs) which are the glial cells of the olfactory system. We evaluated the effects of curcumin on the behaviour of mouse OECs to determine if it could be of use to further enhance the therapeutic potential of OECs. Curcumin, a natural polyphenol compound found in the spice turmeric, is known for its anti-cancer properties at doses over 10 µM, and often at 50 µM, and it exerts its effects on cancer cells in part by activation of MAP kinases. In contrast, we found that low-dose curcumin (0.5 µM) applied to OECs strikingly modulated the dynamic morphology, increased the rate of migration by up to 4-fold, and promoted significant proliferation of the OECs. Most dramatically, low-dose curcumin stimulated a 10-fold increase in the phagocytic activity of OECs. All of these potently stimulated behavioural characteristics of OECs are favourable for neural repair therapies. Importantly, low-dose curcumin gave a transient activation of p38 kinases, which is in contrast to the high dose curcumin effects on cancer cells in which these MAP kinases tend to undergo prolonged activation. Low-dose curcumin mediated effects on OECs demonstrate cell-type specific stimulation of p38 and ERK kinases. These results constitute the first evidence that low-dose curcumin can modulate the behaviour of olfactory glia into a phenotype potentially more favourable for neural repair and thereby improve the therapeutic use of OECs for neural repair therapies.
Noisy Talk ∗

We investigate strategic information transmission with communication error, or noise. Our main finding is that adding noise can improve welfare. With quadratic preferences and a uniform type distribution, welfare can be raised for almost every bias level by introducing a sufficiently small amount of noise. Furthermore, there exists a level of noise that makes it possible to achieve the best payoff that can be obtained by means of any communication device. As in the model without noise, equilibria are interval partitional; with noise, however, coding (the measure of the message space used by each interval of the equilibrium partition of the type space) becomes critically important. K. Communication, information transmission, cheap talk, noise. JEL . C72, D82, D83.
Pharmacokinetics and Tissue Distribution of Anidulafungin in Rats

ABSTRACT This study assessed the tissue distribution of anidulafungin in rats. Anidulafungin rapidly distributed into tissues, achieving peak concentrations within 30 min, and maintained levels above MICs for common pathogens over 72 h. In tissues susceptible to fungal infection (liver, lung, spleen, kidney), exposure was 9- to 12-fold higher than in plasma.