Miracle-dz/UniFAR-FTUs huggingface dataset:
Phenotypes selected during chronic lung infection in cystic fibrosis patients: implications for the treatment of Pseudomonas aeruginosa biofilm infections.

During chronic lung infection of patients with cystic fibrosis, Pseudomonas aeruginosa can survive for long periods of time under the challenging selective pressure imposed by the immune system and antibiotic treatment as a result of its biofilm mode of growth and adaptive evolution mediated by genetic variation. Mucoidy, hypermutability and acquirement of mutational antibiotic resistance are important adaptive phenotypes that are selected during chronic P. aeruginosa infection. This review dicsusses the role played by these phenotypes for the tolerance of biofilms to antibiotics and show that mucoidy and hypermutability change the architecture of in vitro formed biofilms and lead to increase tolerance to antibiotics. Production of high levels of beta-lactamase impairs penetration of beta-lactam antibiotics due to inactivation of the antibiotic. In conclusion, these data underline the importance of biofilm prevention strategies by early aggressive antibiotic prophylaxis or therapy before phenotypic diversification during chronic lung infection of patients with cystic fibrosis.
Inhibition of local nitric oxide synthase increases homeostatic efficiency of tubuloglomerular feedback.

Nephron filtration rate (SNGFR) and proximal tubular reabsorption are coordinated by the processes of tubuloglomerular feedback (TGF) and glomerulotubular balance (GTB). We examined the role of nitric oxide (NO) in TGF and GTB, by delivering the NO synthase inhibitor, NG-monomethyl-L-arginine (L-NMMA) into late proximal nephrons by micropuncture in Inactin-anesthetized euvolemic rats. First, we determined the dependence of SNGFR on late proximal tubular flow rate (VLP) during orthograde microperfusion of Henle's loop downstream from an obstructing wax block (open-loop microperfusion). Second, we examined the homeostatic efficiency of the TGF-GTB system, (i.e., its ability to stabilize VLP) by perturbing VLP in free-flowing nephrons, while using a noninvasive optical technique to measure flow immediately upstream from the perturbation (closed-loop perturbation). Third, we tested whether L-NMMA could alter the afferent signal to TGF by changing the relationship between VLP and the flow rate (VED) or ionic content (CED) of early distal tubular fluid during open-loop microperfusion. During open-loop microperfusion, L-NMMA decreased SNGFR at VLP between 10 and 40 nl/min but did not alter the relationship between VLP and VED or CED. During closed-loop perturbation, L-NMMA did not affect ambient VLP but increased the homeostatic efficiency of the TGF-GTB system. The combined effects on SNGFR and ambient VLP suggest that L-NMMA reduces proximal reabsorption. However, this could account for only a small fraction of the increase in homeostatic efficiency, the greater share of which must be mediated within the juxtaglomerular apparatus. It appears that juxtaglomerular NO exerts an upward pressure on SNGFR and reduces the efficiency of the TGF-GTB system in stabilizing VLP at ambient flow rates under euvolemic conditions.
Retrobulbar circulation in myopic patients with or without myopic choroidal neovascularisation

Aim: To investigate the effect of myopia and myopic choroidal neovascularisation (CNV) on retrobulbar circulation in central retinal artery (CRA) and vein (CRV) and posterior ciliary artery (PCA). Methods: 52 subjects with and without myopia were included in the study. Retrobulbar circulation was measured using colour Doppler imaging. Analysis of correlation of degree of myopia with blood flow velocity parameters was done. Circulatory differences between eyes of patients with unilateral neovascular degenerative myopia were estimated. Results: The analysis of correlation between dioptry and blood flow velocity in the CRA, CRV, and PCA showed a significant positive correlation. Axial length was also significantly correlated with CRA and CRV blood velocity and had a tendency to be correlated with PCA blood velocity. When compared with the fellow eye, the eye with myopic CNV had significantly higher resistivity index (RI) (p=0.048) in the PCA and no significant difference in the circulatory parameters of the CRA and CRV. Conclusion: Central retinal and posterior ciliary blood velocity decreases with the increase of the degree of myopia. PCA RI is higher in myopic CNV.
The development of bystander intentions and social-moral reasoning about intergroup verbal aggression.

A developmental intergroup approach was taken to examine the development of prosocial bystander intentions among children and adolescents. Participants as bystanders (N = 260) aged 8-10 and 13-15 years were presented with scenarios of direct aggression between individuals from different social groups (i.e., intergroup verbal aggression). These situations involved either an ingroup aggressor and an outgroup victim or an outgroup aggressor and an ingroup victim. This study focussed on the role of intergroup factors (group membership, ingroup identification, group norms, and social-moral reasoning) in the development of prosocial bystander intentions. Findings showed that prosocial bystander intentions declined with age. This effect was partially mediated by the ingroup norm to intervene and perceived severity of the verbal aggression. However, a moderated mediation analysis showed that only when the victim was an ingroup member and the aggressor an outgroup member did participants become more likely with age to report prosocial bystander intentions due to increased ingroup identification. Results also showed that younger children focussed on moral concerns and adolescents focussed more on psychological concerns when reasoning about their bystander intention. These novel findings help explain the developmental decline in prosocial bystander intentions from middle childhood into early adolescence when observing direct intergroup aggression.
LncRNA NEAT1 promotes dexamethasone resistance in multiple myeloma by targeting miR‐193a/MCL1 pathway

Although dexamethasone (DEX) remains a first‐line agent for multiple myeloma (MM) therapy, the development of DEX resistance has become an indicator of poor prognosis in MM patients. It is thus urgent to develop strategies to restore the vulnerability of MM to DEX. This study demonstrated long non‐coding RNA (lncRNA) nuclear paraspeckle assembly transcript 1 (NEAT1) was highly expressed in DEX‐resistant myeloma cell lines, and upregulation of NEAT1 was tightly linked to poor prognosis. The in‐depth study revealed that during the development of DEX resistance in these cells, the miR‐193a levels were decreased, which resulted in the increased expression of the target gene myeloid cell leukemia‐1 (MCL1). We also found knockdown of NEAT1, the DEX‐induced sensitivity was enhanced in the resistant cells. Meanwhile, overexpression of NEAT1 increased the DEX‐induced resistance in the sensitive cells. In conclusion, the NEAT1/miR‐193a/MCL1 pathway is closely associated with the development of DEX resistance in myeloma cells, and knockdown of NEAT1 can significantly improve DEX sensitivity in MM.
Some modified results of the subtraction and division operations on interval neutrosophic sets

ABSTRACT An interval neutrosophic set (INS), characterised by the truth, indeterminacy and falsity membership functions, is a powerful structure for handling the uncertain, imprecise and incomplete information existing in the real world in a better way. Under this environment, an attempt is made to define the subtraction and division operations, by imposing some new constrained conditions, after removing the shortcomings of existing operations. The deficiencies of the existing operations are validated through some counterexamples. Further, various desirable properties related to these operations are investigated in detail. Finally, some numerical examples are provided to validate it.
Localized proton MR spectroscopy in infants with urea cycle defect.

SUMMARY Urea cycle defect is an inborn error of ammonium metabolism caused by a deficient activity of the enzymes involved in urea synthesis. Localized short-TE proton MR spectroscopy, performed in two infants who had citrullinemia and ornithine transcarbamylase deficiency, respectively, showed a prominent increase of glutamine/glutamate and lipid/lactate complex in both cases. N-acetylaspartate, total creatine, and myo-inositol were decreased in the infant with citrullinemia. Proton MR spectroscopy provided useful information for the diagnosis and understanding of the pathophysiology of urea cycle enzyme defect.
Concentrations of heavy metals in the tissues of red deer (Cervus elaphus) from the region of Warmia and Mazury, Poland

Cadmium, lead, copper and zinc were quantified using a validated ICP/MS method in the tissues and organs of 82 specimens of red deer of different sexes and ages, which had been hunted at the Great Lakes Land region in the north-eastern of Poland in 2000–01. Copper and zinc occurred in liver, kidney and muscle tissue of red deer at concentrations of 6.4–29, 3.3–7.2 and 1.9–6.4, and of 19–43, 17–41 and 19–64 mg kg−1, respectively, which are considered typical for the species, age and gender compared with values noted for some other wild and domestic ruminant species elsewhere. For cadmium and lead, the concentrations decreased in the order kidney > liver > muscle tissue, with overall means of 2.2, 0.19, and 0.10, 0.31, and 0.26, 0.22 mg kg−1 wet weight, respectively. The cadmium content of the kidney of a proportion of red deer sampled exceeded the legal tolerance limits set in Poland. The means (but not individual animal data) obtained for cadmium in kidney and liver correlated (0.99) with the age of red deer. Also, the lead content of the muscle meat of red deer for many carcasses exceeded the legal limit, which was probably due to contamination from the fine dust particle remains from the lead bullets used.
Clinical experiences of patients with catecholaminergic polymorphic ventricular tachycardia

Abstract Catecholaminergic polymorphic ventricular tachycardia is a rare entity that can occur in children without cardiac disease and with a normal QT interval. It may cause syncope, convulsions, and sudden death during physical activity or emotional distress. We report the clinical features, treatment, and follow-up of 16 children with this diagnosis, emphasizing the potentially fatal nature of the disease. The mean age of patients at the onset of symptoms and at the time of diagnosis was 7.8 plus or minus 2.5 years, and 10.6 plus or minus 3.5 years, respectively. Syncope was the main complaint in 11, and 7 were treated as erroneously as having epilepsy. Diagnosis was confirmed by exercise and/or infusion of isoproterenol. Once the diagnosis was made, we started propranolol in all patients, and added verapamil if ventricular tachycardia was still inducible on a treadmill exercise test. An intracardiac defibrillator was implanted in 4 patients. Of the 16 patients, 4 died suddenly, giving a rate of mortality of 25%. In 2 of those dying suddenly, there was evidence of poor compliance to the recommended treatment. Another 2 patients had been resusciated because of sudden cardiac arrest. Catecholaminergic polymorphic ventricular tachycardia must be considered in the differential diagnosis of syncope in children without heart disease but with a normal QT interval. Medical treatment with propranolol and verapamil may decrease the incidence of arrhythmia. Implantation of intracardiac defibrillators should be considered in those resistant to drug therapy. Delay in diagnosis, and inadequate treatment, can result in sudden cardiac death.
What factors increase the probability of Chinese interventions in intrastate wars?

ABSTRACT This study examines the question: What are the factors that increase the probability of Chinese interference in intrastate wars? Chinese behaviour concerning intrastate wars was examined using multivariate logistic regressions. The analyses included the general behaviour of China regarding interference in intrastate wars, Chinese support of violent non-governmental organizations and of state governments. Both were also studied separately for the Cold War and the post-Cold War eras. Among the covariates that were examined, several emerged as possible explanations for China's behaviour: geographic contiguity, adversary regime type, and China's relative military capabilities. Furthermore, differences were found between Chinese support of violent non-governmental organizations and of governments in intrastate wars. Different results were also obtained for Cold War and post-Cold War eras.
Increased Expression of lncRNA UCA1 and HULC Is Required for Pro-inflammatory Response During LPS Induced Sepsis in Endothelial Cells

Systemic uncontrolled inflammatory response, also termed as sepsis, is responsible for many mortalities. Bacterial endotoxin, lipopolysaccharide (LPS), is a major cause of sepsis in endothelial cells. Even though a lot of research has been done to define underlying mechanisms of LPS induced sepsis, the role of long non-coding RNAs (lncRNAs), a group of >200 kb RNAs in sepsis is not well-defined. Expression of pro-inflammatory mediators IL6, ICAM1, and VCAM1 (which encodes interleukin-6, intercellular adhesion molecule-1, and vascular cell adhesion molecule-1, respectively) were determined following LPS treatment of human dermal microvascular endothelial cells (HMECs) for 24 h to confirm sepsis induction. RNA immunoprecipitation (RIP) analysis was performed using the chromatin modifying proteins (CMPs), heterogeneous nuclear ribonucleoprotein (hnRNP) K and corepressors of the RE-1 silencing transcription factor (coREST) as individual baits. Quantitative real time polymerase chain reaction (qRT-PCR) was performed on RNA isolated from immunoprecipitated pellets for six different lncRNAs. The effect of the differentially expressed lncRNAs were determined by ectopic overexpression of the lncRNAs before induction of sepsis. Expression of IL6, ICAM1, and VCAM1 were significantly upregulated following treatment of the HMECs with LPS for 24 h confirming induction of sepsis. RIP and qRT-PCR analysis revealed that the lncRNAs HULC, UCA1, and MALAT-1 were significantly enriched with the CMPs after sepsis. RNA interference using siRNAs targeting HULC and UCA1, but not MALAT-1, decreased the expression of IL6, ICAM1, and VCAM1 to endogenous levels. Our results were further validated in an in vivo model of sub-lethal LPS-induced sepsis, whereby siRNA mediated knockdown of UCA1 and HULC lncRNAs prevented induction of VCAM1, ICAM1, and IL6, as assayed by immunohistochemistry. Cumulatively, these results suggest that LPS induced in vitro sepsis in endothelial cells and induction of pre-inflammatory mediators are at least in part due to increased expression of the UCA1 and HULC lncRNAs.
Psychosocial aspects of health seeking behaviours of patients with Buruli ulcer in southern Benin

We investigated cultural beliefs and psychosocial factors associated with Buruli ulcer in southern Benin in order to elaborate and deliver appropriate health education messages. We conducted a qualitative study among 130 adults and 30 children in Zou province, a highly endemic region. Focus group interviews of inhabitants, patients and their assistants, health care professionals and traditional healers took place in Dasso, Ouinhi, Sagon and Zagnanado. Drawing sessions followed by individual interviews were organized among school children in Dasso and Sagon. We found that although Buruli ulcer is well known and recognized – even at a very early stage of the disease – and perceived as threatening, most people are reluctant to seek treatment at the health care centre. They are unclear about the origin of the disease (environmental factors or sorcery) and treatment is considered devastating, expensive and ineffective in some cases.
Quality-of-care indicators for early-stage prostate cancer.

PURPOSE Decisions regarding treatment for early-stage prostate cancer are frustrated not only by inadequate evidence favoring one treatment modality but also by the absence of data comparing quality among providers. In fact, the choice of provider may be as important as the choice of treatment. We undertook this study to develop an infrastructure to evaluate variations in quality of care for men with early-stage prostate cancer. METHODS We enlisted several sources to develop a list of proposed quality-of-care indicators and covariates. After an extensive structured literature review and a series of focus groups with patients and their spouses, we conducted structured interviews with national academic leaders in prostate cancer treatment. We then convened an expert panel using the RAND consensus method to discuss and rate the validity and feasibility of the proposed quality indicators and covariates. RESULTS The panel endorsed 49 quality-of-care indicators and 14 covariates, which make up our final list of candidate measures. Several domains of quality are represented in the selected indicators, including patient volume, pretreatment referrals, preoperative testing, interpretation of pathology specimens, and 10-year disease-free survival. Covariates include measures of case-mix, such as patient age and comorbidity. CONCLUSION This study establishes a foundation on which to build quality-of-care assessment tools to evaluate the treatment of early-stage prostate cancer. The next step is to field-test the indicators for feasibility, reliability, validity, and clinical utility in a population-based sample. This work will begin to inform medical decision-making for patients and their physicians.
Creating a Toolkit to Reduce Disparities in Patient Engagement

Background: Patient engagement has become a major focus of health care improvement efforts nationally. Although evidence suggests patient engagement can be beneficial to patients, it has not been consistently defined, operationalized, or translated into practice. Objectives: Our objective was to develop a toolkit to help providers increase patient engagement and reduce disparities in patient engagement. Research Design: We used qualitative interviews and observations with staff at primary care sites nationally to identify patient engagement practices and resources used to engage patients. We then used a modified Delphi process, that included a series of conference calls and surveys, where stakeholders reduced lists of engagement practices based on perceived feasibility and importance to develop a toolkit for patient engagement. Sampling: Sites were selected for interviews and site visits based on the concentration of minority patients served and performance on a measure of patient engagement, with the goal of highlighting practices at sites that successfully serve minority patients. Results: We created a toolkit consisting of patient engagement practices and resources. No identified practice or resource specifically targeted patient engagement of minorities or addressed disparities. However, high-performing, high–minority-serving sites tended to describe more staff training opportunities and staff feedback mechanisms. In addition, low-performing and high–minority-serving sites more often reported barriers to implementation of patient engagement practices. Conclusions: Stakeholders agreed on feasible and important engagement practices. Implementation of this toolkit will be tracked to better understand patient engagement and its effect on patient-centered care and related disparities in care.
Relative and absolute cancer mortality of women in agriculture in northern Italy

Most studies of cancer risk related to agricultural exposures have focused on male operators. Cancer mortality in a cohort of 38 962 women engaged in agriculture (Province of Forlì, 1969–1993) was compared with that of the rest of the female residents using the ratio of age-standardized (Europe) mortality rates (ASR) with 95% confidence interval (CI). Moreover, mortality time trends in both subsets of the population were evaluated. The cohort yielded 798 439 person-years with 2397 cancer deaths. Total ASR ratio was 0.86 (95% CI 0.80–0.92). Only gastric cancer was associated with a significant but declining excess mortality (ASR ratio 1.26; 95% CI 1.11–1.43). Total ASR ratio decreased from 1.07 (95% CI 0.95–1.20) in 1969–1976 to 0.74 (95% CI 0.66–0.82) in 1985–1993. This resulted from a downward mortality trend restricted to the cohort. In particular, mortality from cancers of the oesophagus, stomach and colon/rectum decreased more steeply in the cohort. Mortality from liver cancer decreased only in the cohort. Mortality from cancers of the pancreas, lung, breast, bladder and skin melanoma remained stable in the cohort whilst increasing in the rest of the population. In conclusion, risk excesses previously reported were not confirmed. Agricultural workers qualified as a subset of the female population with atypical, favourable epidemiologic characteristics.
The psychosocial impact associated with diabetes‐related amputation

Research has suggested that the additional impact of a diabetes‐related amputation is associated with poorer physical functioning, poorer psychosocial outcome and greater body image disturbance. However, no study to date has compared patients with diabetes with and without amputation and adequately controlled for additional medical morbidity often found among individuals with an amputation. The aim of this study was to statistically control for any group differences on medical and demographic variables to examine the isolated psychosocial impact of diabetes‐related amputation.
Repeated Evolution of the Pyrrolizidine Alkaloid–Mediated Defense System in Separate Angiosperm Lineages w⃞

Species of several unrelated families within the angiosperms are able to constitutively produce pyrrolizidine alkaloids as a defense against herbivores. In pyrrolizidine alkaloid (PA) biosynthesis, homospermidine synthase (HSS) catalyzes the first specific step. HSS was recruited during angiosperm evolution from deoxyhypusine synthase (DHS), an enzyme involved in the posttranslational activation of eukaryotic initiation factor 5A. Phylogenetic analysis of 23 cDNA sequences coding for HSS and DHS of various angiosperm species revealed at least four independent recruitments of HSS from DHS: one within the Boraginaceae, one within the monocots, and two within the Asteraceae family. Furthermore, sequence analyses indicated elevated substitution rates within HSS-coding sequences after each gene duplication, with an increased level of nonsynonymous mutations. However, the contradiction between the polyphyletic origin of the first enzyme in PA biosynthesis and the structural identity of the final biosynthetic PA products needs clarification.