Miracle-dz/UniFAR-FTUs huggingface dataset:
Long-Term Suppression of Tumor Growth by TNF Requires a Stat1- and IFN Regulatory Factor 1-Dependent IFN-γ Pathway but Not IL-12 or IL-181

Tumor cells engineered to secrete TNF were used as a model to examine how persistently high local concentrations of TNF suppress tumor growth. TNF secretion had no effect on tumor cell proliferation in vitro but caused a very impressive growth arrest in vivo that was dependent on both bone marrow- and non-bone marrow-derived host cells expressing TNFR. Suppression also required an endogenous IFN-γ pathway consisting minimally of IFN-γ, IFN-γ receptor, Stat1, and IFN regulatory factor 1 since mice with targeted disruption of any of the four genes failed to arrest tumor growth. The ability of these mice to suppress tumor growth was restored after they were reconstituted with bone marrow cells from Wt mice. Interestingly, mice lacking the major IFN-γ-inducing cytokines IL-12 and IL-18 or T cells, B cells, and the majority of NK cells that are potential sources of IFN-γ nevertheless inhibited tumor development. Moreover, multiple lines of evidence indicated that local release of IFN-γ was not required to inhibit tumor formation. These results strongly suggest a novel function for the endogenous IFN-γ pathway that without measurable IFN-γ production or activity affects the ability of TNF to suppress tumor development.
Phase II Trial of Etoposide (V), Adriamycin (A), and Cisplatinum (P) in Patients with Metastatic Gastric Cancer

The efficacy and toxicity of a combination of etoposide (100 mg/m2 i.v. on days 1 to 3), Adriamycin (20 mg/m2 i.v. on days 1 and 8) and cisplatinum (40 mg/m2 i.v. on days 2 and 8) repeated every 4 weeks as an outpatient regimen were assessed in 29 consecutive patients with metastatic gastric cancer with measurable disease. Five of these patients were refractory to 5-Fluorouracil, Adriamycin, and Mitomycin C. Three of these previously treated patients responded to the etoposide, Adriamycin, cisplatinum (VAP) therapy. An overall objective response rate of 72.5% was achieved, including 14% that were complete responses. The median duration of response was 6.0 months; median overall survival was 7.2 months, overall one-year survival was 34.4%. He-matologic toxicity was intense, particularly among patients with lower performance status. Three patients died as a consequence of nadir sepsis episodes.
Modelling International Tourism Demand Using Seasonal ARIMA Models

Purpose – The purpose of this study is to establish a seasonal autoregressive integrated moving average model able to capture and explain the patterns and the determinants of German tourism demand in Croatia. Design – The present study is based on the Box-Jenkins approach in building a seasonal autoregressive integrated moving average model intend to describe the behaviour of the German tourists’ flows to Croatia. Approach – The proposed model is a seasonal ARIMA(0,0,0)(1,1,3) model. Findings – The diagnostic checking and the performed tests showed that the estimated seasonal ARIMA(0,0,0)(1,1,3) model is adequate in modelling and analysing the number of German tourists ‘arrivals to Croatia. Originality of the paper – This study provides a seasonal ARIMA model helpful to analyse, understand and forecast German tourists’ flows to Croatia. Such, more detailed and systematic studies should be considered as starting points of future macroeconomic development strategies, pricing strategies and tourism sector routing strategies in Croatia, as a predominantly tourism oriented country. Classification-JEL: L83
This item is the archived peer-reviewed author-version of: Targeting immune checkpoints : new opportunity for mesothelioma treatment?

Malignant pleural mesothelioma is an aggressive cancer linked to asbestos exposure in most patients. Due to the long latency between exposure and presentation, incidence is expected to further increase in the next decade, despite the ban on asbestos import which occurred at the end of last century in industrialized countries. Platinum-based palliative chemotherapy is the only treatment with proven benefit on outcome, resulting in selected patients in a median overall survival of about 1 year. Therefore, there is room for therapeutic improvement using a new strategy to prolong survival. Dealing with cancer cell induced immunosuppression is a promising approach. Reactivating immune responses that are silenced by immune checkpoints recently gained a lot of interest. Checkpoint blockade has already shown promising preclinical and clinical results in several cancer types and is currently also being investigated in mesothelioma. Here, we discuss the expression patterns and mechanisms of action of CTLA-4 and PD-1 as the two most studied and of TIM-3 and LAG-3 as two interesting upcoming immune checkpoints. Furthermore, we review the clinical results of molecules blocking these immune checkpoints and point out their future opportunities with a special focus on mesothelioma.
[The recommendable frequency for performing electrocardiograms in the hypertension patient].

OBJECTIVE To obtain information on how often electrocardiograms (ECG) should be carried out during hypertense patients' follow-up. DESIGN A retrospective, descriptive study. SETTING La Mina Primary Care Centre. PATIENTS Out of 1780 hypertense patients over 14 years old monitored at our Health Centre, 352 were selected by random sampling. MEASUREMENTS AND MAIN RESULTS Their first ECG after the AHT diagnosis was analysed. Those patients with a normal initial ECG, a minimum of one year's monitoring, and absence of a chronic limitation of air flow, diabetes mellitus or cardiopathy were included in the study. The ECGs following the first ECG were analysed sequentially until an anomalous ECG was detected. Final sample: 98 patients (average age 53, SD 12.8; 33 men and 65 women). 89 (91.8%) had light-to-moderate AHT. The average interval between the initial normal ECG and the first pathological ECG was 36 months (SD 16.9). The most common electrocardiographic irregularities were the T minor wave (34.5%), the greater unevenness of the ST (17.2%) and left ventricular hypertrophy (13.8%). A total of 29 patients presented a pathological ECG during an average monitoring period of 61 months (C.I. 95%; 50-72). These were only significantly different from the remaining 69 as regards age. Those patients over 54 (n = 51) had significantly more irregularities (21) than those under 55 (n = 47) (8 irregularities) (p = 0.006), the main increase being between the ages of 55 and 60. CONCLUSIONS The recommendation to carry out an ECG every 2 or 3 years when monitoring a hypertense patient with a normal initial ECG and without additional pathologies, could be extrapolated from our study. The time interval could be shortened for older patients.
Sequence requirements for synthetic peptide-mediated translocation to the nucleus

The abilities of 18 synthetic peptides to target a carrier protein to the nucleus following microinjection into the cytoplasm of HeLa cells were determined. Eight of the sequences chosen for synthesis were based on published nuclear targeting regions as determined by gene fusion and deletion experiments. Six of these sequences were found to be effective when mimicked by a synthetic peptide and conjugated to a carrier protein. One additional peptide was based on a region of lamin L1, a nuclear protein from Xenopus laevis, in which the nuclear targeting region had not been previously investigated. This peptide was also able to target a carrier protein to the nucleus. Eight other peptides which resemble the known targeting signals had little or no nuclear targeting ability. Peptides which were able to target a carrier protein to the nucleus did so within 45 min of injection into the cytoplasm. Two peptides with little or no apparent nuclear targeting ability after 45 min were examined for longer times as well. No increase in nuclear accumulation was observed between 45 min and 4 h after cytoplasmic injection. Comparison of the sequences which were effective at nuclear targeting with those that were not revealed a possible consensus sequence for peptide-mediated nuclear transport.
Comment on "Differential Rescue of Light- and Food-Entrainable Circadian Rhythms"

Fuller et al. (Reports, 23 May 2008, p. 1074) reported that the dorsomedial hypothalamus contains a Bmal1-based oscillator that can drive food-entrained circadian rhythms. We report that mice bearing a null mutation of Bmal1 exhibit normal food-anticipatory circadian rhythms. Lack of food anticipation in Bmal1–/– mice reported by Fuller et al. may reflect morbidity due to weight loss, thus raising questions about their conclusions.
The Thatcher Illusion as a Test of Configural Disruption

Bartlett and Searcy's recent account for the Thatcher illusion suggests that inversion impairs holistic facial information. This illusion is used to compare the effects of inverting and negating faces. Subjects made a speeded response to whether just the mouth and the eyes of a face have been inverted. Performance was found to be slower when faces were inverted rather than upright. Presenting faces in photographic negative also hindered performance implying that this transformation also disrupts holistic facial information.
Father-child Interactional Synchrony in Brazilian Families With Maternal Depression

In this study we were primarily concerned with paternal behavior with a focus on its proximal (immediate causation) and distal (function and evolution) levels of analysis, in the context of maternal depression. Several authors point out the flexibility of paternal caretaking in nature and argue that, in humans, it is facultative and, thus, more open to calculations of maximizing inclusive fitness than maternal behavior (Hrdy, 2014; Storey & Walsh 2011; Storey, Delahunty, McKay, Walsh, & Wilhelm, 2006). In addition, evolutionary approaches of depression offer functional analyses highlighting its adaptive function (Hagen, 1999; Price, 1967). From an evolutionary perspective, postpartum depression can have a signal function communicating mother’s need for extra support when she is unable to cope, especially from the partner (Hagen, 1999, 2002). Our main objective was to examine the associations between paternal behavior, maternal depression and family relationships. We hypothesized that when mothers are depressed, fathers assume a more active role within the family system, increasing investment to compensate for mother’s “partial functioning” due to depression, promoting their child’s well-being and, thus, potentially increasing their inclusive fitness. Forty-six father-child dyads were observed in a free-play situation and assessments of the degree of father-child interactional synchrony (interpersonal distance, visual and body orientation and dyadic involvement) were made. Greater father-child proximity and higher visual attunement, when mothers presented postpartum depression and later depression were found. These results were discussed in relation to the evolutionary hypothesis of depression, Trivers’ Parental Investment Theory and Family System Theory.
Properties of an Inducible C4-Dicarboxylic Acid Transport System in Bacillus subtilis

The transport of the tricarboxylic acid cycle C4-dicarboxylic acids was studied in both the wild-type strain and tricarboxylic acid cycle mutants of Bacillus subtilis. Active transport of malate, fumarate, and succinate was found to be inducible by these dicarboxylic acids or by precursors to them, whereas glucose or closely related metabolites catabolite-repressed their uptake. l-Malate was found to be the best dicarboxylic acid transport inducer in succinic dehydrogenase, fumarase, and malic dehydrogenase mutants. Succinate and fumarate are accumulated over 100-fold in succinic dehydrogenase and fumarase mutants, respectively, whereas mutants lacking malate dehydrogenase were unable to accumulate significant quantities of the C4-dicarboxylic acids. The stereospecificity of this transport system was studied from a comparison of the rates of competitive inhibition of both succinate uptake and efflux in a succinate dehydrogenase mutant by utilizing thirty dicarboxylic acid analogues. The system was specific for the C4-dicarboxylic acids of the tricarboxylic acid cycle, neither citrate nor α-ketoglutarate were effective competitive inhibitors. Of a wide variety of metabolic inhibitors tested, inhibiors of oxidative phosphorylation and of the formation of proton gradients were the most potent inhibitors of transport. From the kinetics of dicarboxylic acid transport (Km approximately 10−4 M for succinate or fumarate in succinic acid dehydrogenase and fumarase mutants) and from the competitive inhibition studies, it was concluded that an inducible dicarboxylic acid transport system mediates the entry of malate, fumarate, or succinate into B. subtilis. Mutants devoid of α-ketoglutarate dehydrogenase were shown to accumulate both α-ketoglutarate and glutamate, and these metabolites subsequently inhibited the transport of all the C4-dicarboxylic acids, suggesting a regulatory role.
The significance of activation markers on CD8 lymphocytes in human immunodeficiency syndrome: staging and prognostic value

The objective of this prospective cohort study was to evaluate the expression of activation markers on CD8 lymphocytes at various clinical stages of HIV infection and to determine the value of these markers in identifying patients likely to have rapidly progressive disease. One hundred and three HI V+ patients, divided into four disease stages, and 34 seronegative controls were evaluated at study entry using flow cytometric immunophenotyping. The HIV patients were followed clinically for disease progression during the following 2 years. CD8 cell numbers and percentage of lymphocytes are increased after HIV infection. Expression of the CD38, HLA‐DR and CD57 markers on CD8 cells was significantly increased in asymptomatic HIV‐infected patients when compared with controls, as was the CDS cell population which did not coexpress Leu‐8. These activation markers were observed to be further increased in patient groups with more clinically advanced infection. The percentage of CD38 on CD8 cells emerged not only as a discriminator of disease severity, but was a strong predictor of progression in asymptomatic, lymphadenopathy and ARC patients. Given the utility of activation markers on CDS lymphocytes in staging disease and predicting clinical outcome, the measurement of these parameters should be considered in the monitoring and management of HIV patients.
Requirement for Intercellular Adhesion Molecule 1 and Caveolae in Invasion of Human Oral Epithelial Cells by Porphyromonas gingivalis

ABSTRACT Porphyromonas gingivalis, a periodontopathic bacterium, is known to invade oral epithelial cells in periodontal lesions, although the mechanism is unclear. In the present study, goat polyclonal anti-intercellular adhesion molecule 1 (anti-ICAM-1) antibody inhibited the invasion of P. gingivalis into KB cells (human oral epithelial cells). Further, the P. gingivalis fimbria, a pathogenic adhesion molecule, bound to recombinant human ICAM-1, as shown by enzyme-linked immunosorbent assay. P. gingivalis was also found to colocalize with ICAM-1 on KB cells, as seen with an immunofluorescence microscope, and the knockdown of ICAM-1 in KB cells resulted in the inhibition of P. gingivalis invasion by RNA interference. In addition, methyl-β-cyclodextrin, a cholesterol-binding agent, inhibited the colocalization of P. gingivalis with ICAM-1 and invasion by the microorganism. The colocalization of caveolin-1, a caveolar marker protein, on KB cells with P. gingivalis was also shown, and the knockdown of caveolin-1 in KB cells caused a reduced level of P. gingivalis invasion. These results suggest that ICAM-1 and caveolae are required for the invasion of P. gingivalis into human oral epithelial cells, and these molecules appear to be associated with the primary stages of the development and progression of chronic periodontitis.
Shape memory alloy servo actuator system with electric resistance feedback and application for active endoscope

A control system for a shape memory alloy (SMA) servo actuator, and its application to a unique medical tool, are considered. It is thought that the electric resistance value of an SMA can be utilized to monitor the transformation of the SMA directly. Therefore, an antagonistic transformation control scheme using electric resistance feedback is proposed and is verified by several experiments. This control scheme reduces the open-loop hysteresis of an SMA actuator and improves greatly its robustness against heat disturbance due to changes in the cooling condition. Research into the application of the method in an active endoscope is reported. It consists of five segments of 13 mm diameter, 40 mm length each. The bending angle of each segment can be controlled individually from outside by using antagonistic electric resistance feedback without any motion sensors. A model for smooth insertion to the colon is verified. <<ETX>>
Self-Reported Headgear Use and Concussions Among Collegiate Men’s Rugby Union Players

The perceived effectiveness of rugby union headgear in reducing concussions in American male collegiate rugby union athletes was assessed. Data collection was conducted by survey method distributed using electronic mail. One hundred and thirty-one men’s club rugby union participants from eight university teams in the United States were surveyed. Demographic data were assessed using frequencies, means, and standard deviations. An ANOVA was used to assess differences in the frequencies of responses between players with concussions and their perception of headgear, with an increase in positive perception of headgear with increased concussions. Player position and years of experience played a role in the number of concussions and use of protective headgear. Seventy-six different athletes reported a concussion while playing, with the majority (51%) not wearing headgear. Athletes who wore headgear experienced 24% of the concussions, compared to 76% of those who did not wear headgear. The incidence of concussions and severity of concussions were perceived as less severe among the group wearing headgear. The general perception of those individuals polled as to the effectiveness of headgear in reducing head injuries was positive.
Dislocation of a primary total hip arthroplasty is more common in patients with a lumbar spinal fusion

Aims Lumbar fusion is known to reduce the variation in pelvic tilt between standing and sitting. A flexible lumbo‐pelvic unit increases the stability of total hip arthroplasty (THA) when seated by increasing anterior clearance and acetabular anteversion, thereby preventing impingement of the prosthesis. Lumbar fusion may eliminate this protective pelvic movement. The effect of lumbar fusion on the stability of total hip arthroplasty has not previously been investigated. Patients and Methods The Medicare database was searched for patients who had undergone THA and spinal fusion between 2005 and 2012. PearlDiver software was used to query the database by the International Classification of Diseases, 9th Revision, Clinical Modification (ICD‐9‐CM) procedural code for primary THA and lumbar spinal fusion. Patients who had undergone both lumbar fusion and THA were then divided into three groups: 1 to 2 levels, 3 to 7 levels and 8+ levels of fusion. The rate of dislocation in each group was established using ICD‐9‐CM codes. Patients who underwent THA without spinal fusion were used as a control group. Statistical significant difference between groups was tested using the chi‐squared test, and significance set at p < 0.05. Results At one‐year follow‐up, 14 747 patients were found to have had a THA after lumbar spinal fusion (12 079 1 to 2 levels, 2594 3 to 7 levels, 74 8+ levels). The control group consisted of 839 004 patients. The dislocation rate in the control group was 1.55%. A higher rate of dislocation was found in patients with a spinal fusion of 1 to 2 levels (2.96%, p < 0.0001) and 3 to 7 levels (4.12%, p < 0.0001). Patients with 3 to 7 levels of fusion had a higher rate of dislocation than patients with 1 to 2 levels of fusion (odds ratio (OR) = 1.60, p < 0.0001). When groups were matched for age and gender to the unfused cohort, patients with 1 to 2 levels of fusion had an OR of 1.93 (95% confidence interval (CI) 1.42 to 2.32, p < 0.001), and those with 3 to 7 levels of fusion an OR of 2.77 (CI 2.04 to 4.80, p < 0.001) for dislocation. Conclusion Patients with a previous history of lumbar spinal fusion have a significantly higher rate of dislocation of their THA than age‐ and gender‐matched patients without a lumbar spinal fusion.
Higher-Level Production of Volatile Fatty Acids In Vitro by Chicken Gut Microbiotas than by Human Gut Microbiotas as Determined by Functional Analyses

ABSTRACT The aim of this study was to determine the relationship between the composition and function of gut microbiota. Here, we compared the bacterial compositions and fermentation metabolites of human and chicken gut microbiotas. Results generated by quantitative PCR (qPCR) and 454 pyrosequencing of the 16S rRNA gene V3 region showed the compositions of human and chicken microbiotas to be markedly different, with chicken cecal microbiotas displaying more diversity than human fecal microbiotas. The nutrient requirements of each microbiota growing under batch and chemostat conditions were analyzed. The results showed that chicken cecal microbiotas required simple sugars and peptides to maintain balanced growth in vitro but that human fecal microbiotas preferred polysaccharides and proteins. Chicken microbiotas also produced higher concentrations of volatile fatty acids than did human microbiotas. Our data suggest that the availability of different fermentable substrates in the chicken cecum, which exist due to the unique anatomical structure of the cecum, may provide an environment favorable to the nourishment of microbiotas suited to the production of the higher-energy metabolites required by the bird. Therefore, gut structure, nutrition, immunity, and life-style all contribute to the selection of an exclusive bacterial community that produces types of metabolites beneficial to the host.
Iodotyrosine dehalogenase 1 (DEHAL1) is a transmembrane protein involved in the recycling of iodide close to the thyroglobulin iodination site

In the thyroid, iodotyrosine dehalogenase acts on the mono and diiodotyrosines released during the hydrolysis of thyroglobulin to liberate iodide, which can then reenter the hormone‐producing pathways. It has been reported that the deiodination of iodotyrosines occurs predominantly in the microsomes and is mediated by NADPH. Recently, two cDNAs, 7401‐ and 7513‐base pairs long that encode proteins with a conserved nitroreductase domain were published in GenBank as iodotyrosine dehalogenase 1 (DEHAL1) and iodotyrosine dehalogenase 1B (DEHAL1B), respectively. We report here our investigation of the localization and activity of one of these isoforms, DEHAL1. DEHAL1 mRNA is highly expressed in the thyroid, is up‐regulated by cAMP, and encodes a transmembrane protein that efficiently catalyzes the NADPH‐dependent deiodination of mono (L‐MIT) and diiodotyrosine (L‐DIT), with greater activity vs. L‐MIT. Iodotyrosine deiodinase was active in HEK293 cells transfected by DEHAL1 cDNA, but not in CHO cells. A fraction of DEHAL1 protein is exposed to the cell surface, as indicated by biotinylation experiments. Immunohistochemistry studies showed that DEHAL1 proteins accumulate at the apical pole of thyrocytes. Taken together, these findings indicate that the deiodination reaction occurs at the apical pole of the thyrocyte and is involved in a rapid iodide recycling process at and/or close to the organification site.