Miracle-dz/UniFAR-FTUs huggingface dataset:
Implementation of the "loaded implant" model in the rat using a miniaturized setup--description of the method and first results.

OBJECTIVE To miniaturize the "loaded implant" model to permit its application to small rodents. In this model, two titanium implants are placed 8 mm apart with their heads protruding from the skin and are forced together by a dedicated actuator. To assess the effect of (i) the post-implantation healing period and the duration of stimulation and (ii) the intratissular strain level on the microtomographical bone parameters BV/TV, Tb.N. , Tb.Th. and BIC. MATERIALS AND METHODS Implants, 1 × 8 mm, were machined, inserted into the tibiae of rats and activated. A total of 123 animals were used. In series 1, the implants were left to heal for 2/4 weeks and then loaded to generate intratissular strains of 1125 ± 5% με for 4/8 weeks. Series 2 had their implants loaded to 750, 1500 and 2250 ± 5% με, respectively. RESULTS Bone to implant contact increased upon loading. In series 1, no difference was observed regarding the duration of healing or the stimulation period. In series 2, at 750 με, the bone parameters did not differ from baseline. At 1500 με, all four parameters increased. At 2250 με, three of four parameters decreased relative to 1500 με. CONCLUSIONS (i) The loaded implant model can be miniaturized to the millimeter range; (ii) in the present model, implant activation beyond 4 weeks did not affect the bone parameters; (iii) mechanical stimulation increased bone to implant contact by up to 20%; (iv) the results obtained are consistent with the concept of an anabolic effect from 750 to 1500 με and deleterious effects at strains in the 2250 με range; and (v) strains at 2250 με did not lead to implant dis-integration.
On the Utility of Context (or the Lack Thereof) for Object Detection

The recurring context in which objects appear holds valuable information that can be employed to predict their existence. This intuitive observation indeed led many researchers to endow appearance-based detectors with explicit reasoning about context. The underlying thesis suggests that with stronger contextual relations, the better improvement in detection capacity one can expect from such a combined approach. In practice, however, the observed improvement in many case is modest at best, and often only marginal. In this work we seek to understand this phenomenon better, in part by pursuing an opposite approach. Instead of going from context to detection score, we formulate the score as a function of standard detector results and contextual relations, an approach that allows to treat the utility of context as an optimization problem in order to obtain the largest gain possible from considering context in the first place. Analyzing different contextual relations reveals the most helpful ones and shows that in many cases including context can help while in other cases a significant improvement is simply impossible or impractical. To better understand these results we then analyze the ability of context to handle different types of false detections, revealing that contextual information cannot ameliorate localization errors, which in turn also diminish the observed improvement obtained by correcting other types of errors. These insights provide further explanations and better understanding regarding the success or failure of utilizing context for object detection.
RCT to evaluate a hyaluronic acid containing gauze pad in leg ulcers of venous or mixed aetiology.

OBJECTIVE To investigate the efficacy and safety of an hyaluronic acid (HA)-impregnated gauze pad compared with a hydrocolloid (HC) dressing, in patients with leg ulcer of venous or mixed aetiology. METHOD A 56-day blind-observer, randomised, multicentre, controlled, non-inferiority trial. Patients were randomised to receive either an HA gauze pad (ialuset gauze pad) or an HC dressing (DuoDERM E). The primary endpoint was the difference between the groups regarding the percentages of patients achieving a reduction of at least 40% of the initial wound surface after 56 days of treatment (visit 5). Secondary endpoints included reduction of wound area, aspect of the wound (percentage of necrotic,fibrinous or granulation tissue), rate of complete ulcer healing, pain intensity, and clinical status of the peri-ulcerous skin. RESULTS In total, 170 patients were included and analysed in the intention-to-treat (ITT) population; 27 patients presented at least one major protocol deviation and were excluded from the per-protocol (PP) population.Therefore, 143 patients constituted the PP population (n=72 and n=71 in the HA gauze pad group and HC dressing group, respectively). At day 56, the confidence interval of the difference between the two groups for the percentage of patients with a reduction of at least 40% of the target ulcer initial surface was [-0.128; 0.164] with a lower limit above the non-inferiority threshold (-0.15). Peri-ulcerous skin was significantly less impaired in the HA gauze pad group for oedema at day 56 (p = 0.04), purpura at day 14 (p = 0.009) and for maceration at day 14 (p = 0.003). Other secondary endpoints were not significantly different between the two groups. Overall, both treatments were well tolerated and adverse events were comparable between the two groups regarding their pattern, frequency, likely relationship to treatment and severity which was mostly mild (grade I) or moderate (grade 2). These results were confirmed in the overall ITT population. CONCLUSION These data support the non-inferiority of the HA gauze pad compared with HC for the primary endpoint.The significant differences in favour of HA gauze pad regarding peri-ulcerous skin changes (oedema, purpura and maceration) may suggest a trend for HA gauze pad to have a better acceptability than the reference HC dressing. DECLARATION OF INTEREST This study was sponsored by Laboratoires Genévrier. Authors received honoraria for their contributions to the study, but have no other conflicts of interests to declare.
PD‐L1 expression is regulated by hypoxia inducible factor in clear cell renal cell carcinoma

In our study, we demonstrate that ccRCC cell lines with impaired function of pVHL to degrade HIFα express elevated levels of PD‐L1. In vitro analysis provided evidence that both reconstitution of pVHL and silencing of HIF2α, but not of HIF1α, lead to reduced PD‐L1 expression. The strong correlation of expression between the HIF2α‐specific HIF target Glut1 and PD‐L1 confirmed this finding in ccRCC cell lines and tissue. Soluble PD‐L1 levels remained constant in the sera of ccRCC patients regardless of the PD‐L1 expression status in their tumors. In conclusion, our data suggest PD‐L1 as HIF2α target, which is upregulated in pVHL deficient ccRCC. The combination of PD‐L1 targeting drugs with HIF inhibiting agents may be an additional option for the treatment of ccRCC.
Development and Psychometric Properties of a Short Situational Urge to Smoke Scale (SUS) for Smoking Adolescents

As urges are associated with positive-social, negative-affective, and habitual situations, we developed a sound scale to assess urges in these situations. In Northeastern Germany in 2005/2006, a sample of 1,093 smoking adolescents from 7th to 10th grade, aged 12–18 years, was used. Reliability analysis and exploratory and confirmatory factor analyses were applied. A three-factorial structure of the final situational urge to smoke scale (SUS) was found. Internal consistency of the scale was high (α = .89). The SUS is a new internally consistent scale that assesses the urge to smoke in adolescents. Further research needs to examine its predictive validity. The study's limitations are noted.
A possible role for 5-phosphoribosyl 1-pyrophosphate in the stimulation of uterine purine nucleotide synthesis in response to oestradiol-17 .

1. It has been reported that the rate of purine nucleotide synthesis de novo in the immature rat uterus is doubled at 6h after administration of oestradiol-17beta. The present work confirms an increased incorporation of glycine and adenine into uterine nucleotides between 2 and 6h after hormone treatment and investigates the mechanism of this response. 2. Activation of regulatory enzymes is unlikely to promote increased nucleotide synthesis: the activities of 5-phosphoribosyl 1-pyrophosphate amidotransferase (EC 2.4.2.14) and adenine phosphoribosyltransferase (EC 2.4.2.7) are the same in uterine extracts from control and oestrogen-treated rats. 3. Therefore it was proposed that oestradiol might promote an increased supply of a rate-limiting substrate. The low oestrogen-sensitive rate of AMP synthesis from adenine and endogenous 5-phosphoribosyl 1-pyrophosphate in the intact uterus compared with the high, oestrogen-insensitive rate in uterine extracts supplemented with 5-phosphoribosyl 1-pyrophosphate is evidence that the supply of 5-phosphoribosyl 1-pyrophosphate limits purine nucleotide formation and may increase after hormone treatment. This proposal is supported by the decrease in AMP synthesis in the whole tissue in the presence of guanine and 7-amino-3-(beta-d-ribofuranosyl)pyrazolo[3,4-d]pyrimidine (formycin). These compounds do not inhibit adenine uptake or adenine phosphoribosyltransferase activity, but they both decrease the availability of 5-phosphoribosyl 1-pyrophosphate, the former by promoting its utilization by hypoxanthine/guanine phosphoribosyltransferase (EC 2.4.2.8) and the latter by inhibiting its synthesis from ribose 5-phosphate and ATP by ribose 5-phosphate pyrophosphokinase (EC 2.7.6.1). 4. It is unlikely that the increased availability of 5-phosphoribosyl 1-pyrophosphate results from hormonal stimulation of ribose 5-phosphate formation. Methylene Blue and phenazine methosulphate both increase ribose 5-phosphate without altering the supply of 5-phosphoribosyl 1-pyrophosphate. 5. The activity of ribose 5-phosphate pyrophosphokinase is low in uterine extracts and increases rapidly in response to oestradiol. Therefore the hormonal activation of the routes of purine nucleotide synthesis both de novo and from preformed precursors may be due, at least in part, to an increased availability of the common rate-limiting substrate 5-phosphoribosyl 1-pyrophosphate, mediated by activation of ribose 5-phosphate pyrophosphokinase.
Evaluation of craniofacial morphology in patients with obstructive sleep apnea using lateral cephalometry and dynamic MRI.

CONTEXT Obstructive sleep apnea (OSA) is a potentially life-threatening disorder, characterized by repeated collapse of the upper airway during sleep with cessation of breathing. The altered mouth breathing produces morphological changes in craniofacial region. AIM This study was designed to compare and validate the craniofacial morphological characteristics in patients with OSA using lateral cephalometry and to investigate the dentofacial characteristics of patients with OSA with respect to the obstructive sites determined by dynamic magnetic resonance imaging (MRI) to more accurately clarify the pathophysiological features. MATERIALS AND METHODS 10 patients with OSA were divided into two groups of five each according to their obstructive site determined by dynamic MRI. (1) Obstruction at the retropalatal and retroglossal region (Rp + Rg group) and (2) obstruction at the retropalatal region (Rp group). Lateral cephalogram both in upright and supine position was taken for all the subjects. In addition, dynamic MRI was performed to identify the sites of obstruction of the upper airway. STATISTICAL ANALYSIS USED Independent t-test was performed to evaluate the significant difference in the upright cephalometric variables between the study and control group and between the two groups. The changes in skeletal and soft tissue parameters with change in posture was assessed within the study and control group by paired t test. P value of ≤ 0.05 was considered as statistically significant. RESULTS The study indicated that the first group of patients with both retropalatal and retroglossal obstruction showed signs of skeletal discrepancy that predisposed to obstruction at the retroglossal level and the soft tissue components like the soft palate and tongue that contributed to retropalatal obstruction. However, the second group of patients with only retropalatal obstruction had primarily soft tissue components associated with increased BMI that contributed to retropalatal obstruction. CONCLUSION Evaluation of craniofacial morphology in OSA patients is bound to help the concerned specialist in recognizing the morphological changes induced by altered sleep pattern so as to provide the appropriate treatment.
Differential expression of carbohydrate blood‐group antigens on rat taste‐bud cells: Relation to the functional marker α‐gustducin

An afferent nerve fiber supplying a taste bud receives input from several taste receptor cells, yet is predominantly responsive to one of the classic taste qualities (salt, acid, sweet, or bitter). This specificity requires recognition between taste receptor cells and nerve fibers that may be mediated by surface markers correlating with function. In an effort to identify potential markers, we used immunofluorescence and confocal microscopy to examine expression of the oligosaccharide blood‐group antigens Lewisb, A, and H type 2 in taste buds of the rat oral cavity. We compared the distributions of these antigens with that of α‐gustducin, a G‐protein subunit implicated in responses to sweet‐ and bitter‐tasting substances. The A and Lewisb antigens were present only on spindle‐shaped cells whose apical processes reached the taste pore. These antigens were not present on epithelial cells surrounding taste buds, and Lewisb was not found elsewhere in the digestive tract. Lewisb and A were not removed by lipid extraction, suggesting that they are present on glycoproteins rather than glycolipids. All Lewisb‐positive cells expressed α‐gustducin, but only a fraction of α‐gustducin–positive cells expressed Lewisb. The fraction of taste‐bud cells expressing Lewisb decreased in the order: vallate papillae > foliate papillae > nasoincisor duct. The epiglottis had almost no taste‐bud cells that expressed Lewisb. The A antigen appeared on taste‐bud cells that also expressed α‐gustducin in the order: foliate and vallate papillae > nasoincisor duct and epiglottis > fungiform papillae. In addition, the A antigen was present on many cells that lacked α‐gustducin in foliate and vallate papillae. In vallate papillae, cells expressed either A or Lewisb, but not both. Lewisb appears to be restricted to differentiated light cells that also express α‐gustducin and may be involved in intercellular interactions of these cells. J. Comp. Neurol. 415:230–239, 1999. © 1999 Wiley‐Liss, Inc.
The Short Stalk Length of Highly Pathogenic Avian Influenza H5N1 Virus Neuraminidase Limits Transmission of Pandemic H1N1 Virus in Ferrets

ABSTRACT H5N1 influenza viruses pose a pandemic threat but have not acquired the ability to support sustained transmission between mammals in nature. The restrictions to transmissibility of avian influenza viruses in mammals are multigenic, and overcoming them requires adaptations in hemagglutinin (HA) and PB2 genes. Here we propose that a further restriction to mammalian transmission of the majority of highly pathogenic avian influenza (HPAI) H5N1 viruses may be the short stalk length of the neuraminidase (NA) protein. This genetic feature is selected for when influenza viruses adapt to chickens. In our study, a recombinant virus with seven gene segments from a human isolate of the 2009 H1N1 pandemic combined with the NA gene from a typical chicken-adapted H5N1 virus with a short stalk did not support transmission by respiratory droplet between ferrets. This virus was also compromised in multicycle replication in cultures of human airway epithelial cells at 32°C. These defects correlated with a reduction in the ability of virus with a short-stalk NA to penetrate mucus and deaggregate virions. The deficiency in transmission and in cleavage of tethered substrates was overcome by increasing the stalk length of the NA protein. These observations suggest that H5N1 viruses that acquire a long-stalk NA through reassortment might be more likely to support transmission between humans. Phylogenetic analysis showed that reassortment with long-stalk NA occurred sporadically and as recently as 2011. However, all identified H5N1 viruses with a long-stalk NA lacked other mammalian adapting features and were thus several genetic steps away from becoming transmissible between humans.
European Surveillance of Antimicrobial Consumption (ESAC): outpatient penicillin use in Europe (1997-2009).

BACKGROUND Data on 13 years (1997-2009) of outpatient penicillin use were collected from 33 European countries within the European Surveillance of Antimicrobial Consumption (ESAC) project and analysed in detail. METHODS For the period 1997-2009, data on outpatient use of systemic penicillins aggregated at the level of the active substance were collected using the Anatomical Therapeutic Chemical (ATC)/defined daily dose (DDD) method (WHO, version 2011) and expressed in DDD per 1000 inhabitants per day (DID). For detailed analysis of trends over time, seasonal variation and composition of outpatient penicillin use in 33 European countries, we distinguished between narrow-spectrum penicillins (NSP), broad-spectrum penicillins (BSP), penicillinase-resistant penicillins (PRP) and combinations with β-lactamase inhibitors (COP). RESULTS Total outpatient penicillin (ATC group J01C) use in 2009 varied by a factor of 3.8 between the countries with the highest (16.08 DID in France) and lowest (4.23 DID in the Russian Federation) use. COP represented 45.8%, BSP 40.7%, NSP 10.8% and PRP 2.6% of total European outpatient penicillin use. Total outpatient penicillin use significantly increased over time by 1.53 (SD 0.71) DID between 1997 and 2009. COP (mainly co-amoxiclav) increased by 2.17 (SD 0.40) DID, which was the result of its absolute increase as well as the observed shift from NSP and BSP towards COP. This increase exceeded 10% in 20 countries, where it coincided with a similar decrease in either BSP (15 countries) or NSP (5 countries). CONCLUSIONS Penicillins represented the most widely used antibiotic subgroup in all 33 participating countries, albeit with considerable variation in their use patterns. For Europe, a continuous increase in overall penicillin use and of COP use was observed during the period 1997-2009.
Induced Pluripotent Stem Cells with Six Reprogramming Factors from Prairie Vole, Which is an Animal Model for Social Behaviors

Prairie voles show strong pair bonding with their mating partners, and they demonstrate parental behavior toward their infants, indicating that the prairie vole is a unique animal model for analysis of molecular mechanisms of social behavior. Until a recent study, the signaling pathway of oxytocin was thought to be critical for the social behavior of prairie voles, but neuron-specific functional research may be necessary to identify the molecular mechanisms of social behavior. Prairie vole pluripotent stem cells of high quality are essential to elucidate the molecular mechanisms of social behaviors. Generation of high-quality induced pluripotent stem cells (iPSCs) would help to establish a genetically modified prairie vole, including knockout and knock-in models, based on the pluripotency of iPSCs. Thus, we attempted to establish high-quality prairie vole-derived iPSCs (pv-iPSCs) in this study. We constructed a polycistronic reprogramming vector, which included six reprograming factors (Oct3/4, Sox2, Klf4, c-myc, Lin28, and Nanog). Furthermore, we evaluated the effect of six reprogramming factors, which included Oct3/4 with the transactivation domain (TAD) of MyoD. Implantation of the pv-iPSCs into immunodeficient mice caused a teratoma with three germ layers. Furthermore, the established pv-iPSCs tested positive for stem cell markers, including alkaline phosphatase activity (ALP), stage-specific embryonic antigen (SSEA)-1, and dependence on leukemia inhibitory factor (LIF). Our data indicate that our newly established pv-iPSCs may be a useful tool for genetic analysis of social behavior.
Species-Typical Patterns of Infant Contact, Sleeping Site Use and Social Cohesion among Nocturnal Primates in Africa

This paper provides a checklist and summary of what is currently known of the variation in infant contact, sleeping site preference and aspects of social cohesion in the nocturnal primates of Africa. Genera and species are compared, based on previously unpublished field observations and a review of the literature. There is a clear pattern of similarity between the species within each genus and distinct differences between genera. Species in the same genus tend to be ecologically equivalent and replace each other allopatrically, whereas species in different genera are more likely to be sympatric, with up to 6 species living together. Maximum sympatry within genera is found in Otolemur and Galagoİdes, where species are ecologically divergent. This may reflect an ancient origin of species within these genera or suggest that further taxonomic revision is required at the generic level. Some data are recorded for the first time for species that have only recently been separated (cryptic species), but some taxa remain very poorly known. It is concluded that field studies are still at an elementary stage and further research with radio tracking is urgently needed in the face of rapidly declining habitats.
Induction and characterization of metallothionein in chicken epiphyseal growth plate cartilage chondrocytes

Following exposure to cadmium or zinc, chickens were sacrificed and the liver, kidney, and bone epiphyseal growth plates harvested. When cytosolic extracts of the growth plate cartilage were fractionated by gel filtration chromatography, a protein with high metal‐binding capacity and low ultraviolet (UV) absorbance eluted in the same position as liver metallothionein (MT) and a MT standard. Cd or Zn treatment resulted in a 25‐fold or 5‐fold induction in growth plate MT, respectively. In liver the greatest level of MT induction was seen with short‐term Cd exposures. In contrast, MT levels in the growth plate increased as the duration of Cd exposure increased. Induction of MT in growth plate chondrocyte cell cultures was observed for media Cd concentrations of ≥0.1 μM and Zn concentrations of ≥100 μM. Basal and inducible levels of MT declined through the culture period and were lowest in the terminally differentiated mineralized late stages of the culture. Alkaline phosphatase activity was also lowest in the late‐stage cultures, while total cellular protein increased throughout the culture period. Treatment of chondrocytes with Zn prior to Cd exposure resulted in a protective induction of MT. Pre‐treatment of chondrocytes with dexamethasone resulted in suppressed synthesis of MT upon Cd exposure and greater Cd toxicity. Both Cd and Zn resulted in significantly increased levels of MT mRNA in chondrocyte cell cultures. Dexamethasone treatment resulted in an approximate 2‐ to 3‐fold increase in MT mRNA. This is contrary to the finding that MT protein levels were decreased by dexamethasone. The findings suggest that an increased rate of MT degradation in dexamethasone‐treated and late‐stage chondrocyte cultures may be associated with the terminally differentiated phenotype. J. Cell. Biochem. 68:110–120, 1998. © 1998 Wiley‐Liss, Inc.