Miracle-dz/UniFAR-FTUs huggingface dataset:
The role of exercise ventilation in clinical evaluation and risk stratification in patients with chronic heart failure.

BACKGROUND Patients with chronic heart failure (CHF) are characterised by an increased ventilatory response to exercise. The role of exercise ventilation in the risk stratification and evaluation of patients with CHF has not yet been established. AIM To examine the relationship between exercise ventilation indices and clinical parameters of CHF and to assess the prognostic value of the ventilatory response to exercise. METHODS The study group consisted of 87 patients with CHF (72 males, mean age 58 years) with a mean left ventricular ejection fraction of 32%. Ten patients were in NYHA class I, 38 - in NYHA class II, 34 - in NYHA class III, and 5 - in NYHA class IV. The control group consisted of 20 patients without CHF (13 males, mean age 58 years, mean LVEF - 61%). All studied subjects underwent maximal exercise test with gas-exchange measurement. The following parameters were analysed: peak exercise oxygen consumption [peak VO(2) (ml/kg/min)], VE-VCO(2) index [a coefficient of linear regression analysis depicting an association between ventilation (VE) and carbon dioxide production (VCO(2)) during exercise] and VE/VCO(2) ratio at peak exercise to VE/VCO(2) ratio while at rest (VE/VCO(2 peak/rest)). RESULTS Ventilatory response indices were significantly higher in patients with CHF compared with controls: VE-VCO(2) - 37.9+/-11.1 vs 27.1+/-4.1; VE-VCO(2 peak/rest) - 0.89+/-0.14 vs 0.75+/-0.10 (p<0.001). In CHF patients a significant positive correlation between ventilatory response parameters and NYHA class (VE-VCO(2) - r=0.52; VE/VCO(2 peak/rest) - r=0.47) and a negative correlation with peak VO(2) (VE-VCO(2) - r=-0.52; VE/VCO(2 peak/rest) - r=-0.49) were noted (p<0.0001 for all correlations). No correlation was found between ventilatory parameters and echocardiographic variables or CHF aetiology. During the follow-up period lasting at least 12 months, 17 (22%) patients died. In the univariate Cox model, NYHA class III-IV, decreased peak VO(2) and increased VE-VCO(2) and VE/VCO(2 peak/rest) values were significantly associated with the risk of death. The multivariate analysis revealed that VE/VCO(2 peak/rest) > or =1.0 was the adverse prognostic factor, independent of peak VO(2) (p=0.02) and NYHA class (p=0.01). The Kaplan-Meier analysis showed that prognosis during the 18-month follow-up period in patients with enhanced exercise ventilation was worse than in the remaining patients (59% survival in patients with VE/VCO(2 peak/rest) > or =1.0 59% vs 91% survival in patients with VE/VCO(2 peak/rest) <1.0, p=0.001). CONCLUSIONS In patients with stable CHF simple exercise ventilation parameters may provide important clinical and prognostic information.
Allergen‐stimulated expression of CD154 (CD40 ligand) on CD3+ lymphocytes in atopic, but not in nonatopic individuals. Modulation by bacterial lipopolysaccharide

The intention of this study was to mimic a naturally occurring stimulation by allergens and bacterial infection in order to determine whether specific allergen‐induced, inflammatory responses may be changed or modified by bacterial products. Blood leukocytes from six atopic and six nonatopic individuals were examined for their surface expression of CD154, CD11a, and HLA‐DR molecules and for secretion of IgE, eosinophil cationic protein (ECP), and the cytokines interleukin (IL)‐4 and IL‐5. Signals through CD154 are required for activation and proliferation of effector cells associated with the allergic, inflammatory response. HLA‐DR and CD11a/CD18‐mediated interactions are also involved in T‐ and B‐cell functions. Birch‐pollen (BP) allergens induced CD154 expression on CD3‐positive lymphocytes only in atopic individuals. In nonatopics, the expression of CD154 could be induced only after exposure to BP and subsequent lipopolysaccharide (LPS) stimulation. Levels of CD154 expression were always higher in atopics than nonatopics. CD11a and HLA‐DR expressions were upregulated, irrespective of atopic state, after BP and/or LPS stimulation. The increased secretion of IL‐5 and total IgE in BP‐supplemented cell cultures indicated that an allergic response had occurred. In conclusion, the results of this report do not support the hypothesis of a changed inflammatory response stimulated by the combined action of bacteria and allergens, as compared to allergen provocation alone.
Effect of granulocyte-stimulating factors on marrow of adult patients with musculoskeletal malignancies: incidence and MRI findings.

OBJECTIVE Our goal was to determine the incidence and pattern of red marrow reconversion on MRI of adults receiving granulocyte-stimulating factors as part of their chemotherapy regimen for primary musculoskeletal neoplasms and correlate the changes with WBC counts. MATERIALS AND METHODS Twenty-five adults with soft-tissue sarcomas (n = 15) or primary bone tumors (n = 10) who underwent chemotherapy that included granulocyte-stimulating factors formed the study group. Two radiologists retrospectively evaluated the MRI studies by consensus before and after therapy to determine the presence of changes consistent with red marrow reconversion. Changes were categorized by appearance on T1- and T2-weighted images for location, pattern, and extent of marrow involvement. WBC counts at the time of MRI were recorded. Records were examined for evidence of marrow-infiltrating tumors or metastases. RESULTS Ten (40%) of the 25 patients underwent bone marrow changes consistent with red marrow reconversion. In seven (70%) of 10 patients, the changes were diffuse in visualized bones and simulated diffuse marrow-infiltrative tumor. In three (30%) of 10 patients, the changes were focal, simulating metastases. T2 signal prolongation was identified in the marrow reconversion in nine patients (90%), although all had shortened T1 signal. Four patients (40%) had elevated WBC counts at the time of the MRI after therapy, but all had shortened T1 signal. Four patients (40%) had elevated WBC counts at the time of the MRI after therapy, five (50%) had normal counts, and one (10%) had a below-normal count. No osseous metastases or marrow-infiltrating tumors were found during follow-up. CONCLUSION Forty percent of patients showed marrow changes mimicking tumor on MRI that were attributable to red marrow reconversion, which correlated moderately with WBC response.
The challenges of behavioural insights for effective policy design

ABSTRACT Behavioural insights are becoming increasingly popular with policy practitioners. Findings and methods originally provided by cognitive psychology and later behavioural economics have found use in the formulation of public policies. Their most popularised application has emerged under the auspices of libertarian paternalism in the form of ‘nudging’. Its proponents claim to provide a new instrument to facilitate the formulation of effective and evidence-based policy, taking people’s actual behaviour into account from the outset, while preserving their liberty to choose. This article reviews the origins of libertarian paternalism and the behavioural insights it builds on and takes a critical look at the foundations nudging relies on as a policy tool. It also discusses the ongoing efforts to build policy capacity to integrate behavioural insights and experimental methods in the creation of public policy. Behavioural insights offer a powerful tool to reshape and design new evidence-based policy. However, designers ought to be aware of the underlying assumptions on individual behaviour, the broadness of the mandate the nudging approach claims and the challenges they pose for design effectiveness.
Targeting the MAPK–RAS–RAF signaling pathway in cancer therapy

Introduction: The MAPK pathway comprises several key signaling components and phosphorylation events that play a role in tumorigenesis. These activated kinases transmit extracellular signals that regulate cell growth, differentiation, proliferation, apoptosis and migration functions. Alteration of the RAS–RAF–MEK–ERK–MAPK (RAS–MAPK) pathway has been reported in human cancer as a result of abnormal activation of receptor tyrosine kinases or gain-of-function mutations mainly in the RAS or RAF genes. These pathways are considered potential therapeutic targets for cancer treatment. Recently, several small-molecule inhibitors targeting this pathway have been developed and are currently being tested in clinical trials. Areas covered: The biological role of the RAS–MAPK pathway, the consequence of its disregulation and the development of small-molecule inhibitors. The rationale for targeting the RAS–MAPK pathway and the application and the results of various inhibitory molecules as anticancer agents in clinical trials. Expert opinion: Inhibitors of MEK and particularly of RAF kinases have shown effectiveness in clinical trials with manageable side effects. RAS and BRAF genes need to be analyzed for mutations as markers of response to treatments and to avoid paradoxical effects. Further characterization of the RAS–MAPK molecular mechanisms regulation in malignant cells or underlying the acquired resistance to RAF inhibitors will facilitate development of novel combination therapies.
Comparison of Results of Detection of Rhinovirus by PCR and Viral Culture in Human Nasal Wash Specimens from Subjects with and without Clinical Symptoms of Respiratory Illness

ABSTRACT Human rhinoviruses (HRV) cause acute upper respiratory illness. The frequency of HRV-associated illnesses appears greater when PCR assays are used to detect rhinoviruses. The present study performed PCR-based detection of HRV upon entry of subjects into respiratory syncytial virus and parainfluenza type 3 vaccine trials when subjects were symptom-free and upon subsequent development of clinical symptoms of respiratory illness during the trial. The background of HRV PCR positivity in symptom-free individuals (30/139 [22%]) was only slightly lower than in those with respiratory illness (28/77 [36%]). For subjects with multiple samples, it was estimated that HRV was detectable by PCR for approximately 100 days before, during, and after clinical symptoms were documented. PCR is a remarkably more sensitive method of detecting HRV than is tissue culture. The presence of HRV RNA may not always reflect an association with infectious virus production. The limited association of HRV RNA with illness suggests caution in assigning causality of HRV PCR positivity to clinical symptoms of respiratory illness.
Use of Trans-Retinoic Acid in the Treatment of Acute Promyelocytic Leukemia

Objective To discuss acute promyelocytic leukemia (APL) and review the literature concerning differentiation treatment of APL with trans-retinoic acid (t-RA). Data Sources English-language articles concerning APL or its treatment with t-RA were identified with a MEDLINE search. Study Selection All studies available at the time of article preparation, which addressed t-RA treatment in APL, were selected. Data Extraction Data extraction and assessment were performed subjectively by the authors. An extensive discussion of specific study details is included in the article. Data Synthesis APL is a unique subset of acute myelogenous leukemia and is typified by an accumulation of malignant promyelocytes in the bone marrow. Within the granulocyte cell cycle of a patient with APL, differentiation has been halted at the level of the promyelocyte, preventing formation of mature granulocytes. Upon treatment with traditional cytotoxic chemotherapy, complete remission rates of approximately 70 percent, with a five-year survival ranging from 25 to 40 percent have been achieved. In most patients with APL, a characteristic chromosomal t(15q+;17q-) translocation has been found, which may be responsible for the production of an aberrant retinoic acid receptor-alpha. Therefore, t-RA induction therapy has been investigated and has produced promising results. Administration of t-RA in dosages of 45–100 mg/m2/d has induced complete remissions. The apparent mechanism of t-RA is the induction of promyelocyte differentiation and maturation. The most common adverse effects noted have been dry skin, cheilitis, and headaches. Conclusions Upon consideration of the initial trials, t-RA appears to be a promising and unique treatment for APL.
The effects of emotional salience, cognitive effort and meta-cognitive beliefs on a reality monitoring task in hallucination-prone subjects.

OBJECTIVES A tendency to externalize internal information on reality monitoring tasks has been documented in psychiatric patients with hallucinations. Furthermore, previous studies suggest that factors such as the emotional salience of the material, cognitive effort and meta-cognitive beliefs are important contributory factors in this tendency to externalize internal information on reality monitoring tasks. However, few studies have investigated these aspects in hallucination-prone subjects. Also, these factors have never been examined simultaneously. In the following study we wished to examine the effects of emotional salience, cognitive effort and meta-cognitive beliefs on reality monitoring functioning in hallucination-prone subjects. DESIGN Between-participants group design. METHOD One hundred normal subjects were administered a reality monitoring task. Words were presented by the experimenter. After each word, subjects were asked to say the first word that came to their mind. Words varied in terms of emotional valence and cognitive effort (high cognitive effort for words requiring longer latency times to associate a word and vice versa). Following a delay, words were presented consisting of those already presented by the experimenter or the subject (old) and those never presented before (new). For each word, subjects were required to identify whether the word was old or new. If the word was identified as old, subjects were required to identify the source of the word (subject or experimenter). Subjects also completed a questionnaire assessing meta-cognitive beliefs. RESULTS Subjects were grouped according to their scores on a revised and elaborated version of the Launay-Slade Hallucinations Scale (LSHS). Those with scores within the top 25% were included in the hallucination-prone group (HP) (N = 25), whereas scores within the lower 25% were included in the non-hallucination-prone group (NHP) (N = 25). Results showed that the HP subjects had significantly more source discrimination errors than NHP subjects for self-generated items. In other words, HP subjects tended to misattribute to the experimenter items that they had produced themselves. This pattern was especially marked with emotionally charged material and with words that required more cognitive effort. In addition, HP subjects scored significantly higher on a scale assessing meta-cognitive beliefs compared with NHP subjects. Finally, scores on a scale assessing meta-cognitive beliefs were positively associated with source discrimination errors. CONCLUSIONS These results suggest that cognitive effort, emotional salience and meta-cognitive beliefs all play a prominent role in the externalizing bias in hallucination-prone subjects. The results also provide evidence for the validity of the idea of a continuity between hallucination-prone subjects and psychotic patients with hallucinations on reality monitoring tasks, including a number of contributing factors in the occurrence of hallucinations.
Histochemical study of Encephalitozoon cuniculi spores in the kidneys of naturally infected New Zealand rabbits

Encephalitozoon cuniculi is an important microsporidian pathogen that is considered an emergent, zoonotic, and opportunistic. It infects both domestic and laboratory rabbits, generating severe chronic interstitial and granulomatous nephritis with fibrosis and granulomatous encephalitis. Encephalitozoonosis is diagnosed in paraffin-embedded sections by examining the spores in the host tissues. The spores are difficult to observe when the samples are stained with hematoxylin and eosin (H&E), particularly when there is an inflammatory reaction and tissue damage. The spores are easily mistaken for other microorganisms, such as fungi (yeasts), protozoa, and bacteria. In our study, we used kidney samples from E. cuniculi–positive rabbits and employed 14 recommended histologic stains for detecting microsporidia spores: alcian blue, calcofluor white, Giemsa, Gram, Grocott, H&E, Luna, Luxol fast blue, Masson trichrome, modified trichrome stain (MTS), periodic acid–Schiff reaction (PAS), Van Gieson, Warthin–Starry (WS), and Ziehl–Neelsen (ZN). We concluded that MTS and Gram stain, detected by light microscopy, and calcofluor white stain, detected by ultraviolet light microscopy, are the best stains for detecting spores of E. cuniculi in paraffin-embedded tissues from infected rabbits. These stains were superior to WS, ZN, Giemsa, and PAS for identifying spores without background “noise” or monochromatic interference. Also, they allow individual spores to be discerned in paraffin-embedded tissues. MTS allows observation of the polar tube, polaroplast, and posterior vacuole, the most distinctive parts of the spore.
Males Shorten the Life Span of C. elegans Hermaphrodites via Secreted Compounds

Battle of the Sexes In many species, males compete with one another to propagate their own DNA, often to the detriment of females (see the Perspective by Promislow and Kaeberlein). Shi and Murphy (p. 536, published online 19 December) discovered that mating in Caenorhabditis species causes mothers to shrink and die soon after they have ceased producing progeny. Males appear to hijack the longevity and stress resistance pathways normally employed by the mothers to slow reproduction and somatic aging in times of stress. Maures et al. (p. 541, published online 29 November) explored why the presence of abundant mating-competent males causes a decrease in the life span of nematodes of the opposite sex and found that a secreted substance, possibly a pheromone, reproduced the effect of the males when transferred in the culture medium. Detection of pheromones from a female fruit fly is enough to cause changes in metabolism, reduce resistance to starvation, and shorten the life span of male flies. Gendron et al. (p. 544, published online 29 November) report that the signals from the female appear to be recognized by sensory receptors on the legs of male flies. Male nematodes produce a soluble signal that shortens the life span of worms of the opposite sex. [Also see Perspective by Promislow and Kaeberlein] How an individual’s longevity is affected by the opposite sex is still largely unclear. In the nematode Caenorhabditis elegans, the presence of males accelerated aging and shortened the life span of individuals of the opposite sex (hermaphrodites), including long-lived or sterile hermaphrodites. The male-induced demise could occur without mating and required only exposure of hermaphrodites to medium in which males were once present. Such communication through pheromones or other diffusible substances points to a nonindividual autonomous mode of aging regulation. The male-induced demise also occurred in other species of nematodes, suggesting an evolutionary conserved process whereby males may induce the disposal of the opposite sex to save resources for the next generation or to prevent competition from other males.
Lermoyez's Syndrome: Histopathologic Report of a Case

This paper reports findings in a pair of temporal bones from a patient with clinical evidence of Lermoyez's syndrome, a rare variant of Meniere's disease. Endolymphatic hydrops is limited to the basal turn of the cochlea and saccule in Lermoyez's syndrome, but more generalized in Meniere's disease.
High levels of portal TNF-alpha during abdominal aortic surgery in man.

During shock or multiple organ dysfunction syndrome, translocation of bacteria and/or lipopolysaccharide (LPS) from the ischaemic gut might occur and could explain the excess of cytokine production detectable in plasma. To test this hypothesis, we studied a model of mild gut ischaemia due to bowel manipulation and aortic clamping in patients undergoing abdominal aortic surgery (n = 14). Per-operative levels of LPS and cytokines were measured before clamping and after reperfusion, and compared in systemic and portal blood. Systemic levels of LPS and cytokines were measured in a control group of patients undergoing internal carotid surgery (n = 7). Portal LPS was detectable (i.e., > 12 pg/ml) in 36% of the patients undergoing aortic surgery after bowel manipulation, and in 71% after clamp release. Similar levels of LPS were observed in portal and systemic blood after clamp release. Circulating tumour necrosis factor alpha (TNF-alpha) was observed in all patients undergoing aortic surgery. Levels of portal TNF-alpha were higher than those in systemic blood after bowel manipulation as well as after reperfusion (P = 0.02 and 0.007, respectively). LPS was never detected in control patients and TNF-alpha was detectable in only two out of seven patients. Mean levels of IL-6 were similar in the two groups, with a peak on the day following surgery, confirming that circulating IL-6 is associated with any surgical procedures. Our data indicate that bowel manipulation, aortic clamping and reperfusion lead to similar levels of portal and systemic circulating LPS. (ABSTRACT TRUNCATED AT 250 WORDS)
Proximal flow to middle cerebral artery is associated with higher thrombus density in terminal internal carotid artery occlusion

Proximal collaterals may determine the composition of occluding thrombi in acute ischemic stroke (AIS) in addition to source, hematocrit, time, and medication. Here, we performed a retrospective study of 39 consecutive patients with radiological evidence of I‐, L‐, and T‐type terminal internal carotid artery occlusion. Middle cerebral artery (MCA) thrombus density was assessed on noncontrast enhanced CT and proximal collaterals on CT angiography. In patients with presence of proximal collaterals to the MCA we detected more hyperdense clots (P = 0.003) and a higher frequency of leptomeningeal collaterals (P = 0.008). We expand the spectrum of factors that potentially determine clot perviousness and evolution of ischemic stroke.
Hyperhomocysteinemia in Bipolar Depression: Clinical and Biochemical Correlates

Background: Depression may be associated with elevated homocysteine (HCY) levels. Procedures aiming at its decrease, i.e. supplementation with folic acid or vitamin B12, have antidepressant effect. Both depression and elevated HCY can increase cardiovascular risk. In this study, clinical and biochemical factors, including markers of endothelial function, in relation to hyperhomocysteinemia, in patients with bipolar depression during acute episode were studied. Method: One hundred and twelve patients (24 male, 88 female), aged 20-78 (mean 51 ± 14 years), with depressive episode in the course of bipolar mood disorder have been included. The assays were made of serum concentrations of HCY, vitamin B12, folic acid as well as markers of endothelial function such as E-selectin and intracellular adhesion molecule-1 (ICAM-1). Results: Hyperhomocysteinemia (>15 mM) was found in 50 patients (45%), significantly more frequently in male (67%) than in female subjects (39%). Female patients with hyperhomocysteinemia were significantly older than the remaining ones. A significant inverse correlation between HCY level and concentration of folic acid and vitamin B12 as well as with E-selectin and ICAM-1 was observed. Conclusion: The results point to a significant prevalence of hyperhomocysteinemia in bipolar depressed patients during an acute episode. They also corroborate the correlation between increased concentration of HCY and lower level of vitamin B12 and folic acid. An unexpected finding of negative correlation of HCY level with markers of endothelial functions in such patients is discussed in view of current concepts of the role of HCY in various conditions.