Miracle-dz/UniFAR-FTUs huggingface dataset:
ADDRESS (ADministration of DRotrecogin alfa [activated] in Early stage Severe Sepsis) long-term follow-up: One-year safety and efficacy evaluation*

Objective:To demonstrate that drotrecogin alfa (activated) has an acceptable safety profile 1 yr from randomization. Design:One-year follow-up of patients participating in a placebo-controlled clinical study of drotrecogin alfa (activated) in severe sepsis patients at low risk of death (the ADDRESS study). Setting:The study was conducted at 516 hospitals in 34 countries. Patients:The study included 2,640 patients. Interventions:One-year follow-up was performed as an addendum to the placebo-controlled ADDRESS study. Treatment groups were compared using the chi-square test and Kaplan-Meier estimates. Measurements and Main Results:Survival status at 1 yr was obtained for 90% of patients enrolled in the study (n = 2,376). The difference in mortality rate between drotrecogin alfa (activated) and placebo patients was numerically smaller at 1 yr (34.2% and 34.0%, respectively, p = .94) than at 28 days (18.5% and 17.0%, respectively, p = .34). In the subgroups defined by organ dysfunction class (single or multiple) and Acute Physiology and Chronic Health Evaluation II score (<25 or ≥25), the differences in mortality rate between treatment groups at 1 yr were consistent with those observed at 28 days; no significant differences in mortality rates between treatment groups were observed. No additional serious adverse events were reported during the period between hospital discharge and 1 yr. Conclusions:No increased risk of death or evidence of harm at 1 yr was associated with drotrecogin alfa (activated) administration in patients with severe sepsis at lower risk of death.
The β-Glucan Receptor Dectin-1 Promotes Lung Immunopathology during Fungal Allergy via IL-22

Sensitization to fungi, such as the mold Aspergillus fumigatus, is increasingly becoming linked with asthma severity. We have previously shown that lung responses generated via the β-glucan receptor Dectin-1 are required for lung defense during acute, invasive A. fumigatus infection. Unexpectedly, in an allergic model of chronic lung exposure to live A. fumigatus conidia, β-glucan recognition via Dectin-1 led to the induction of multiple proallergic (Muc5ac, Clca3, CCL17, CCL22, and IL-33) and proinflammatory (IL-1β and CXCL1) mediators that compromised lung function. Attenuated proallergic and proinflammatory responses in the absence of Dectin-1 were not associated with changes in Ido (IDO), Il12p35/Ebi3 (IL-35), IL-10, or TGF-β levels. Assessment of Th responses demonstrated that purified lung CD4+ T cells produced IL-4, IL-13, IFN-γ, and IL-17A, but not IL-22, in a Dectin-1–dependent manner. In contrast, we observed robust, Dectin-1–dependent IL-22 production by unfractionated lung digest cells. Intriguingly, the absence of IL-22 alone mimicked the attenuated proallergic and proinflammatory responses observed in the absence of Dectin-1, suggesting that Dectin-1–mediated IL-22 production potentiated responses that led to decrements in lung function. To this end, neutralization of IL-22 improved lung function in normal mice. Collectively, these results indicate that the β-glucan receptor Dectin-1 contributes to lung inflammation and immunopathology associated with persistent fungal exposure via the production of IL-22.
The anatomy of the reproductive system in male Dutch rabbits (Oryctolagus cuniculus) with special emphasis on the accessory sex glands

The morphology and microscopic anatomy of the reproductive organs and colliculus seminalis of the male rabbit are described and illustrated. Special attention is given to the accessory sex glands, because not all have been accurately identified previously. The terminology suggested for the accessory glands (with other terms commonly used in the literature in parentheses) follows: glandula vesicularis (glandula seminalis, vesicula seminalis), proprostata (glandula vesicularis, coagulating gland, prostata), prostata, paraprostata (glandula Cowperi superior), glandula bulbourethralis (glandula Cowperi inferior). The English equivalents are vesicular, proprostate, prostate, paraprostate and bulbourethral glands. Organs were obtained from 39 adult Dutch‐belted rabbits that averaged 2,023 g in bodyweight. Organ weights (means and standard deviations) were as follows: testis, 2.035 ± 0.529 g; caput epididymidis, 0.264 ± 0.087 g; corpus epididymidis, 0.046 ± 0.019 g; cauda epididymidis, 0.398 ± 0.123 g; proximal part of the ductus deferens, 0.098 ± 0.026 g; ampulla of the ductus deferens, 0.177 ± 0.069 g; vesicular gland, 0.529 ± 1.169 g; proprostate gland, 0.633 ± 0.304 g; prostate gland, 0.411 ± 0.181 g; paraprostate gland, 0.040 ± 0.019 g; bulbourethral gland, 0.390 ± 0.133 g; and epididymal fat pad, 0.545 ± 0.339 g. Correlations among organ weights were calculated and interrelationships among them and bodyweight are discussed.
Enterotoxigenic Potential ofStaphylococcus intermedius

ABSTRACT Staphylococcal food poisoning (SFP) caused by enterotoxigenic staphylococci is one of the main food-borne diseases. In contrast to Staphylococcus aureus, a systematic screening for the enterotoxins has not yet been performed on the genomic level for the coagulase-positive species S.intermedius. Therefore, the enterotoxigenic potential of 281 different veterinary (canine, n = 247; equine,n = 23; feline, n = 9; other,n = 2) and 11 human isolates of S.intermedius was tested by using a multiplex PCR DNA-enzyme immunoassay system targeting the staphylococcal enterotoxin genes sea, seb, sec,sed, and see. Molecular results were compared by in vitro testing of enterotoxin production by two immunoassays. A total of 33 (11.3%) S.intermedius isolates, including 31 (12.6%) canine isolates, 1 equine isolate, and 1 human isolate, tested positive for the sec gene. In vitro production of the respective enterotoxins was detected in 30 (90.9%) of these isolates by using immunological tests. In contrast, none of 65 veterinary specimen-derived isolates additionally tested and comprising 13 (sub)species of coagulase-negative staphylococci were found to be enterotoxigenic. This study shows on both molecular and immunological levels that a substantial number of S.intermedius isolates harbor the potential for enterotoxin production. Since evidence for noninvasive zoonotic transmission of S. intermedius from animal hosts to humans has been documented, an enterotoxigenic role of this microorganism in SFP via contamination of food products may be assumed.
Organization of orosensory responses in the nucleus of the solitary tract of rat.

1. The receptive field and topographic organization of single orosensory neurons located throughout the rostral division of the nucleus of the solitary tract (rNST) was studied by determining their responsiveness to gustatory stimulation of the entire oral cavity and to gustatory and mechanical stimulation of restricted oral regions. The rNST contained roughly equal numbers of two distinct populations of orosensory neurons, one responsive exclusively to oral mechanical stimulation (M neurons), the other to gustatory stimulation (G neurons). Some G neurons also responded to oral somatosensory stimuli, but usually less vigorously than to gustatory stimuli. The distribution of these two populations of rNST neurons was topographically organized: G neurons were centered anteriorly and medially to M neurons. 2. Eight of 44 G neurons responded only when the whole oral cavity was stimulated, but the remaining 36 cells responded to circumscribed stimulation of taste buds on the anterior tongue (AT), foliate papillae of the posterior tongue, nasoincisor ducts, retromolar mucosa (RM), or soft palate (SP). Overall, AT and SP stimulation were the most effective, and RM stimulation the least effective, for activating nucleus of the solitary tract (NST) G neurons. 3. Approximately half of the G neurons for which a receptive field could be defined (N = 36) responded to stimulation of a single taste receptor subpopulation, but the remaining neurons received convergent input from two or more taste bud groups. The receptive field configurations for convergent G neurons were orderly: convergence occurred preferentially between receptor subpopulations either within the anterior oral cavity (AO) or the posterior oral cavity (PO). An AO-PO distinction also was reflected in the topographic organization of gustatory responses. The mean location of neurons responding optimally to AO gustatory stimulation was more anterior in the NST, and also tended to be more lateral and ventral than the location of neurons that responded optimally to PO stimulation. 4. Forty-four rNST M neurons responded to innocuous mechanical stimulation of restricted areas of the tongue, palate, buccal mucosa, or periodontium. Stimulation of the hard palate and circumvallate papilla were most effective, whereas periodontal stimulation was least effective for activating these cells. 5. A majority (32 of 44) of rNST M neurons responded to stimulation of more than one of the oral sites tested. (ABSTRACT TRUNCATED AT 400 WORDS)
The effect of individual enabling and support on empowerment and depression severity in persons with affective disorders: outcome of a randomized control trial

Abstract Purpose: To evaluate the effect of Individual Enabling and Support (IES) on empowerment and depression severity as compared to Traditional Vocational Rehabilitation (TVR) in people with affective disorders at 12 months follow-up. Additionally, longitudinal changes within the intervention groups and the correlation over time between empowerment and depression severity were evaluated. Method: A single-blind randomized controlled trial of two intervention groups, IES (n = 33) and TVR (n = 28), was performed with measurement points at baseline, 6, and 12 months. Individuals with affective disorders, including depression and bipolar disorder diagnoses were included. The Empowerment Scale and Montgomery–Åsberg Depression Self-Rating Scale were administered, and Intention-To-Treat analysis was applied. The study was registered with the trial number ISRCTN93470551. Result: There was a statistically significant difference between the intervention groups on empowerment and depression severity at 12 months. Within-group analysis showed that IES-participants increased their perceived empowerment and decreased their depression severity between measurement points, this was not seen among TVR-participants. A moderate, inverse relationship was detected between empowerment and depression. Conclusion: IES is more effective in increasing empowerment and decreasing depression severity after a 12-month intervention than is TVR. This study was limited by a small sample size and larger trials in different contexts are needed.
Exploring the relationship between reflectance red edge and chlorophyll content in slash pine.

Chlorophyll is a key indicator of the physiological status of a forest canopy. However, its distribution may vary greatly in time and space, so that the estimation of chlorophyll content of canopies or branches by extrapolation from leaf values obtained by destructive sampling is labor intensive and potentially inaccurate. Chlorophyll content is related positively to the point of maximum slope in vegetation reflectance spectra which occurs at wavelengths between 690-740 nm and is known as the "red edge. " The red edge of needles on individual slash pine (Pinus elliottii Engelm.) branches and in whole forest canopies was measured with a spectroradiometer. Branches were measured on the ground against a spectrally flat reflectance target and canopies were measured from observation towers against a spectrally variable understory and forest floor. There was a linear relationship between red edge and chlorophyll content of branches (R(2) = 0.91). Measurements of the red edge and this relationship were used to estimate the chlorophyll content of other branches with an error that was lower than that associated with the calorimetric (laboratory) method. There was no relationship between the red edge and the chlorophyll content of whole canopies. This can be explained by the overriding influence of the understory and forest floor, an influence that was illustrated by spectral mixture modeling. The results suggest that the red edge could be used to estimate the chlorophyll content in branches, but it is unlikely to be of value for the estimation of chlorophyll content in canopies unless the canopy cover is high.
Harmonics mitigation of dead time effects in PWM converters using a repetitive controller

In order to prevent the power switching devices (e.g., the Insulated-Gate-Bipolar-Transistor, IGBT) from shoot-through in voltage source converter during a switching period, a dead time is added either in the hardware drivers of the IGBTs or implemented in the software Pulse-Width Modulation (PWM) scheme. Both methods will lead to a degradation of the injected current power quality. Thus, the harmonics induced by the dead time have to be compensated in order to achieve a satisfactory current as required by the standards. In this paper, a repetitive controller has been introduced to eliminate the dead-time effect in grid-connected PWM converters. The repetitive controller has been plugged into a proportional resonant based fundamental controller. Compared with the traditional dead-time compensation solutions, the repetitive controller can effectively compensate the dead-time harmonics as well as other low-order distortions, and also it is a simple method without hardware modifications. Experimental results are demonstrating the advantages of the proposed dead-time effect mitigation method compared to the resonant based harmonic compensator.
Recombinant Nematode Anticoagulant Protein c2, a Novel Inhibitor of Tissue Factor-Factor VIIa Activity, Abrogates Endotoxin-Induced Coagulation in Chimpanzees

Summary Systemic activation of coagulation leading to disseminated intravascular coagulation (DIC) is an important feature in patients with severe sepsis. Tissue factor has been shown to play a primary role in this pathological response, as revealed by the use of specific inhibitors and antagonists of the tissue factor/factor VIIa pathway. This class of agents has been demonstrated to attenuate the coagulation response in human volunteers with induced low-grade endotoxemia and to reduce mortality in primate models of Gram-negative sepsis. The efficacy of these agents in attenuating the activation of coagulation and formation of microvascular thrombosis in sepsis may depend on the mechanism of inhibition. Here we demonstrate the efficacy of recombinant nematode anticoagulant protein c2 (rNAPc2) that specifically inhibits the tissue factor/factor VIIa complex by a novel mechanism, in a model of endotoxin-induced coagulation activation in chimpanzees. Administration of a low dose of Gram-negative endotoxin induced marked increases of thrombin generation as measured by plasma levels of prothrombin activation fragment F1+2 and thrombin-antithrombin complexes, which were completely blocked by rNAPc2. In chimpanzees receiving rNAPc2 alone, there was a significant reduction in the activation of factor X but not factor IX, compared to animals receiving placebo. In contrast to the effect of rNAPc2 on thrombin generation, there was no effect of this inhibitor on the well known enhanced systemic fibrinolytic response induced by endotoxin. In conclusion, the recombinant peptide rNAPc2 is an effective inhibitor of tissue factor-driven thrombin generation during low grade endotoxemia. These results suggest that rNAPc2 may be a promising therapeutic option to inhibit coagulation activation in patients with sepsis.
The involvement of medial septum 5-HT1 and 5-HT2 receptors on ACPA-induced memory consolidation deficit: Possible role of TRPC3, TRPC6 and TRPV2

The present study evaluates the roles of serotonergic receptors of the medial septum on amnesia induced by arachidonylcyclopropylamide (ACPA; as selective cannabinoid CB1 receptor agonist) in adult male Wistar rats. Cannulae were implanted in the medial septum of the brain of the rats. The animals were trained in a passive avoidance learning apparatus, and were tested 24 hours after training for step-through latency. Results indicated that post-training medial septum administration of CP94253 (5-HT1B/1D receptor agonist) and cinancerine (as 5-HT2 receptor antagonist) reduced the step-through latency showing an amnesic response, while GR127935 (5-HT1B/1D receptor antagonist) and αm5htm (as 5-HT2A/2B/2D receptor agonist) did not alter memory consolidation by themselves. On continuing the test, the results showed that CP94253 increased and GR127935 did not alter ACPA (0.02 µg/rat)-induced memory impairment, respectively. Other data indicated that αm5htm induced a modulatory effect, while cinancerine restored ACPA-induced amnesia. Using SKF-96365 (inhibitor of transient receptor potential TRPC3/6 and TRPV2 channels) demonstrated that TRPC3, TRPC3 and TRPV2 channels have a significant role, according to our results.
Toll-like receptor 9 protects non-immune cells from stress by modulating mitochondrial ATP synthesis through the inhibition of SERCA2

Toll‐like receptor 9 (TLR9) has a key role in the recognition of pathogen DNA in the context of infection and cellular DNA that is released from damaged cells. Pro‐inflammatory TLR9 signalling pathways in immune cells have been well investigated, but we have recently discovered an alternative pathway in which TLR9 temporarily reduces energy substrates to induce cellular protection from stress in cardiomyocytes and neurons. However, the mechanism by which TLR9 stimulation reduces energy substrates remained unknown. Here, we identify the calcium‐transporting ATPase, SERCA2 (also known as Atp2a2), as a key molecule for the alternative TLR9 signalling pathway. TLR9 stimulation reduces SERCA2 activity, modulating Ca2+ handling between the SR/ER and mitochondria, which leads to a decrease in mitochondrial ATP levels and the activation of cellular protective machinery. These findings reveal how distinct innate responses can be elicited in immune and non‐immune cells—including cardiomyocytes—using the same ligand‐receptor system.
High Resolution 1H NMR-based Metabolomics Indicates a Neurotransmitter Cycling Deficit in Cerebral Tissue from a Mouse Model of Batten Disease*

The neuronal ceroid lipofuscinoses (NCLs) constitute a range of progressive neurological disorders primarily affecting children. Although six of the causative genes have been characterized, the underlying disease pathogenesis for this family of disorders is unknown. Using a metabolomics approach based on high resolution 1H NMR spectroscopy of the cortex, cerebellum, and remaining regions of the brain in conjunction with statistical pattern recognition, we report metabolic deficits associated with juvenile NCL in a Cln3 knock-out mouse model. Tissue from Cln3 null mutant mice aged 1–6 months was characterized by an increased glutamate concentration and a decrease in γ-amino butyric acid (GABA) concentration in aqueous extracts from the three regions of the brain. These changes are consistent with the reported altered expression of genes involved in glutamate metabolism in older mice and imply a change in neurotransmitter cycling between glutamate/glutamine and the production of GABA. Further variations in myo-inositol, creatine, and N-acetyl-aspartate were also identified. These metabolic changes were distinct from the normal aging/developmental process. Together, these changes represent the first documented pre-symptomatic symptoms of the Cln3 mouse at 1 month of age and demonstrate the versatility of 1H NMR spectroscopy as a tool for phenotyping mouse models of disease.
Chronic Inflammation in Benign Prostate Tissue Is Associated with High-Grade Prostate Cancer in the Placebo Arm of the Prostate Cancer Prevention Trial

Background: Chronic inflammation is hypothesized to influence prostate cancer development, although a definitive link has not been established. Methods: Prostate cancer cases (N = 191) detected on a for-cause (clinically indicated) or end-of-study (protocol directed) biopsy, and frequency-matched controls (N = 209), defined as negative for cancer on an end-of-study biopsy, were sampled from the placebo arm of the Prostate Cancer Prevention Trial. Inflammation prevalence and extent in benign areas of biopsy cores were visually assessed using digital images of hematoxylin and eosin–stained sections. Logistic regression was used to estimate associations. Results: Of note, 86.2% of cases and 78.2% of controls had at least one biopsy core (of three assessed) with inflammation in benign areas, most of which was chronic. Men who had at least one biopsy core with inflammation had 1.78 [95% confidence interval (CI), 1.04–3.06] times the odds of prostate cancer compared with men who had zero cores with inflammation. The association was stronger for high-grade disease (Gleason sum 7–10, N = 94; OR, 2.24; 95% CI, 1.06–4.71). These patterns were present when restricting to cases and controls in whom intraprostatic inflammation was the least likely to have influenced biopsy recommendation because their prostate-specific antigen (PSA) was low (<2 ng/mL at biopsy). Conclusion: Inflammation, most of which was chronic, was common in benign prostate tissue, and was positively associated with prostate cancer, especially high grade. The association did not seem to be due to detection bias. Impact: This study supports an etiologic link between inflammation and prostate carcinogenesis, and suggests an avenue for prevention by mitigating intraprostatic inflammation. Cancer Epidemiol Biomarkers Prev; 23(5); 847–56. ©2014 AACR.
Vasopressinergic Regulation of the Hypothalamic Pituitary Adrenal Axis and Stress Adaptation

Vasopressin (VP) stimulates pituitary ACTH secretion through interaction with receptors of the V1b subtype (V1bR, V3R), located in the plasma membrane of the pituitary corticotroph, mainly by potentiating the stimulatory effects of corticotropin releasing hormone (CRH). Chronic stress paradigms associated with corticotroph hyperresponsiveness lead to preferential expression of hypothalamic VP over CRH and upregulation of pituitary V1bR, suggesting an important role for VP during adaptation of the hypothalamic–pituitary–adrenal (HPA) axis to stress. Vasopressinergic regulation of ACTH secretion depends on the number of V1bRs as well as coupling of the receptor to phospholipase C (PLC) in the pituitary. Regulation of V1bR gene transcription may involve a number of regulatory elements in the promoter region, of which a GAGA box was shown to be essential. Although V1bR gene transcription is necessary to maintain V1bR mRNA levels, the lack of correlation between VP binding and V1bR mRNA suggests that regulation of mRNA translation is a major regulatory step of the number of V1bRs. V1bR translation appears to be under tonic inhibition by upstream minicistrons and positive regulation through protein kinase C (PKC) activation of an internal ribosome entry site (IRES) in the 5′ untranslated region (5′UTR) of the mRNA. The data provide mechanisms by which regulation of hypothalamic VP and pituitary V1bR content contribute to controlling HPA axis activity during chronic stress.
High voltage conversion ratio, switched C & L cells, step-down DC-DC converter

The paper presents a high voltage conversion ratio DC-DC step-down topology obtained from a classical buck converter associated with an input switched-capacitor cell and an output switched-inductor cell. Analytical descriptions, the voltage and current limits of the main components are synthesized in a comparative form, related to the classical buck structure, in order to emphasis the advantages of the proposed converter. Digital simulations and experimental results obtained with a built prototype are compared. From the first evaluation, the proposed converter is expected to be effectively used at input to output voltage ratios higher than 20.