Miracle-dz/UniFAR-FTUs huggingface dataset:
Biodistribution and Clearance of Stable Superparamagnetic Maghemite Iron Oxide Nanoparticles in Mice Following Intraperitoneal Administration

Nanomedicine is an emerging field with great potential in disease theranostics. We generated sterically stabilized superparamagnetic iron oxide nanoparticles (s-SPIONs) with average core diameters of 10 and 25 nm and determined the in vivo biodistribution and clearance profiles. Healthy nude mice underwent an intraperitoneal injection of these s-SPIONs at a dose of 90 mg Fe/kg body weight. Tissue iron biodistribution was monitored by atomic absorption spectroscopy and Prussian blue staining. Histopathological examination was performed to assess tissue toxicity. The 10 nm s-SPIONs resulted in higher tissue-iron levels, whereas the 25 nm s-SPIONs peaked earlier and cleared faster. Increased iron levels were detected in all organs and body fluids tested except for the brain, with notable increases in the liver, spleen, and the omentum. The tissue-iron returned to control or near control levels within 7 days post-injection, except in the omentum, which had the largest and most variable accumulation of s-SPIONs. No obvious tissue changes were noted although an influx of macrophages was observed in several tissues suggesting their involvement in s-SPION sequestration and clearance. These results demonstrate that the s-SPIONs do not degrade or aggregate in vivo and intraperitoneal administration is well tolerated, with a broad and transient biodistribution. In an ovarian tumor model, s-SPIONs were shown to accumulate in the tumors, highlighting their potential use as a chemotherapy delivery agent.
Cardiopulmonary fitness in children with congenital heart diseases versus healthy children

Objective We aimed to compare the cardiopulmonary fitness of children with congenital heart diseases (CHD) with that of age-adjusted and gender-adjusted controls. We also intended to identify clinical characteristics associated with maximum oxygen uptake (VO2max) in this population. Methods and results We included in a cross-sectional multicentre study a total of 798 children (496 CHD and 302 controls) who underwent a complete cardiopulmonary exercise test (CPET). The association of clinical characteristics with VO2max was studied using a multivariate analysis. Mean VO2max in the CHD group and control represented 93%±20% and 107%±17% of predicted values, respectively. VO2max was significantly lower in the CHD group, overall (37.8±0.3vs 42.6±0.4 mL/kg/min, P<0.0001) and for each group (P<0.05). The mean VO2max decline per year was significantly higher in CHD than in the controls overall (−0.84±0.10 vs −0.19±0.14 mL/kg/min/year, P<0.01), for boys (−0.72±0.14vs 0.11±0.19 mL/kg/min/year, P<0.01) and for girls (−1.00±0.13 vs −0.55±0.21 mL/kg/min/year, P=0.05). VO2max was associated with body mass index, ventilatory anaerobic threshold, female gender, restrictive ventilatory disorder, right ventricle systolic hypertension, tricuspid regurgitation, the number of cardiac catheter or surgery procedures, and the presence of a genetic anomaly. Conclusions Although the magnitude of the difference was not large, VO2max among children with CHD was significantly lower than in normal children. We suggest performing CPET in routine follow-up of these patients. Trial registration number ClinicalTrials.gov NCT01202916; Post-results.
The Atypical Response Regulator AtvR Is a New Player in Pseudomonas aeruginosa Response to Hypoxia and Virulence

ABSTRACT Two-component systems are widespread in bacteria, allowing adaptation to environmental changes. The classical pathway is composed of a histidine kinase that phosphorylates an aspartate residue in the cognate response regulator (RR). RRs lacking the phosphorylatable aspartate also occur, but their function and contribution during host-pathogen interactions are poorly characterized. AtvR (PA14_26570) is the only atypical response regulator with a DNA-binding domain in the opportunistic pathogen Pseudomonas aeruginosa. Macrophage infection with the atvR mutant strain resulted in higher levels of tumor necrosis factor alpha secretion as well as increased bacterial clearance compared to those for macrophages infected with the wild-type strain. In an acute pneumonia model, mice infected with the atvR mutant presented increased amounts of proinflammatory cytokines, increased neutrophil recruitment to the lungs, reductions in bacterial burdens, and higher survival rates in comparison with the findings for mice infected with the wild-type strain. Further, several genes involved in hypoxia/anoxia adaptation were upregulated upon atvR overexpression, as seen by high-throughput transcriptome sequencing (RNA-Seq) analysis. In addition, atvR was more expressed in hypoxia in the presence of nitrate and required for full expression of nitrate reductase genes, promoting bacterial growth under this condition. Thus, AtvR would be crucial for successful infection, aiding P. aeruginosa survival under conditions of low oxygen tension in the host. Taken together, our data demonstrate that the atypical response regulator AtvR is part of the repertoire of transcriptional regulators involved in the lifestyle switch from aerobic to anaerobic conditions. This finding increases the complexity of regulation of one of the central metabolic pathways that contributes to Pseudomonas ubiquity and versatility.
Nestin expression and in vivo proliferative potential of tanycytes and ependymal cells lining the walls of the third ventricle in the adult rat brain

There is a disagreement in the literature concerning the degree of proliferation of cells in the walls of the third ventricle (3rdV) under normal conditions in the adult mammalian brain. To address this issue, we mapped the cells expressing the neural stem/progenitor cell marker nestin along the entire rostrocaudal extent of the 3rdV in adult male rats and observed a complex distribution. Abundant nestin was present in tanycyte cell bodies and processes and also was observed in patches of ependymal cells as well as in isolated ependymal cells throughout the walls of the 3rdV. However, we observed very limited ependymal cell or tanycyte proliferation in normal adult rats as determined by bromodeoxyuridine (BrdU) incorporation or the expression of Ki‐67. Moreover, fewer than 13% of the cells that were BrdU‐positive (BrdU+) or Ki‐67‐positive (Ki‐67+) expressed nestin. These observations stand in contrast to those made in the subventricular zone of the lateral ventricle (SVZ) and subgranular zone of the hippocampal formation (SGZ), where cell proliferation measured by BrdU incorporation or Ki‐67 expression is observed frequently in cells that also express nestin. Thus, while ependymal cell or tanycyte cell proliferation can be promoted by the addition of mitogens, dietary modifications or other in vivo manipulations, the proliferation of ependymal cells and tanycytes in the walls of the 3rdV is very limited in the normal adult male rat brain.
Targeting the bone marrow microenvironment in acute leukemia

Abstract Despite individual differences between certain leukemias, the overall survival rate in acute leukemia remains low at approximately 40%. Novel therapeutics, including targeted therapies like tyrosine kinase inhibitors, have been incorporated into treatment regimens, but most have failed at eradicating leukemic stem cells (LSCs). The causes of disease relapse, progression, and resistance to chemotherapy are as yet not entirely clear but thought to be linked to protection in the bone marrow microenvironment (BMM). In this review, we summarize current knowledge on the BMM in acute leukemias and examine the ongoing efforts to target the BMM, which include treatment strategies targeting (a) leukemia–BMM interactions, (b) leukemia–cell intrinsic pathways influenced by the BMM, and (c) direct BMM targeting strategies. It is likely that the future ploy against leukemia will involve these and other innovative strategies designed to eradicate the last remaining warrior – the LSC.
A clinical review of communication training for haematologists and haemato‐oncologists: a case of art versus science

The art of communication at times seems at odds with the science of medicine. Poor communication is associated with risks for patient and physician. Communication skills are highly relevant for haematologists and are associated with increased physician and patient satisfaction, positive psychosocial outcomes and possible health outcomes. Medical communication training has recently become widespread but is largely restricted to junior medical professionals. In haematology, the proliferation of high quality communication skills is low and there are few interventions catering for the required skillset. A review identified five applicable interventions for haematologists. There is variation in intervention length and structure, and most studies measure targeted skill fidelity rather than patient outcomes. Work on motivation and empowerment holds potential for haematological conditions, but is largely absent from care. This review highlights the need for new interventions for haematologists which focus on producing and maintaining positive patient outcomes.
On the significance of analysing duty cycle saturation nonlinearity in LCL filter control systems

LCL filters in grid connected front end converters are desired to contain very low or zero damping resistors to obtain efficiency benefits, however, the associated control system development becomes a challenging task. Of particular significance is the consideration of duty cycle saturation, which if not carefully considered, can have a significant effect on the overall operation of LCL filter systems. The main objective of this paper is to emphasize and demonstrate the significance of explicit consideration of duty cycle saturation nonlinearity in LCL filter control system development. The paper also contains a stability analysis that is performed using the nonlinear Describing Function approach. Describing function method can be used to predict existence of limit cycles in closed loop LCL systems that are obtained without proper consideration of duty cycle saturation nonlinearity. It can also be used to confirm stability properties of a controller designed with due consideration to duty cycle saturation.
The genus Microplinthus, with description of four new species (Coleoptera: Curculionidae: Molytinae)

The genus Microplinthus Zherikhin, 1987 is revised. It is assigned to the tribe Aminyopini Voss, 1956, based on the female genitalia and the presence of appendiculate claws in one species. The following new species are described: M. parbatensis sp. n. (Central Nepal); M. kaligandaki sp. n. (Central Nepal); M. shiva sp. n. (India: Darjeeling); M. laurae sp. n. (India: Darjeeling; Sik- kim; Central-western Nepal? ). The genus is apparently the sister group to Falsanchonus Zherikhin, 1987. Mutual relationships among the nine species of Microplinthus are suggested based on a phylogenetic analysis.
Functional abdominal pain disorders in children

ABSTRACT Introduction: Chronic abdominal pain is a common problem in pediatric practice. The majority of cases fulfill the Rome IV criteria for functional abdominal pain disorders (FAPDs). At times, these disorders may lead to rather serious repercussions. Area covered: We have attempted to cover current knowledge on epidemiology, pathophysiology, risk factors related to pathophysiology, clinical evaluation and management of children with FAPDs. Expert commentary: FAPDs are a worldwide problem with a pooled prevalence of 13.5%. There are a number of predisposing factors and pathophysiological mechanisms including stressful events, child maltreatment, visceral hypersensitivity, altered gastrointestinal motility and change in intestinal microbiota. It is possible that the environmental risk factors intricately interact with genes through epigenetic mechanisms to contribute to the pathophysiology. The diagnosis mainly depends on clinical evaluation. Commonly used pharmacological interventions do not play a major role in relieving symptoms. Centrally directed, nonpharmacological interventions such as hypnotherapy and cognitive behavioral therapy have shown both short and long term efficacy in relieving pain in children with FAPDs. However, these interventions are time consuming and need specially trained staff and therefore, not currently available at grass root level. Clinicians and researchers should join hands in searching for more pragmatic and effective therapeutic modalities to improve overall care of children with FAPDs.
THE EFFECTS OF CHRONIC LEAD POISONING ON THE VALUES OF HYPERTENSION IN CHILDREN

Introduction: During the treatment of Roma children from Kosovska Mitrovica suffering from chronic lead poisoning (which began in the sec- ond half of the last decade), hypertension has also been observed. The examination and treatment were con- ducted under the patronage of World Health Organiza- tion, Ministry of Health of the Republic of Serbia and local administration. Aim of this work is show corre- lation between lead levels in blood and hypertension in children. Materials and methods: Lead from capil- lary blood flow was measured by Lead care analyzer. Extracted blood from a vein measured lead level in the toxicological laboratory of the Institute "Karajovi}" Belgrade. The pressure was measured by standard de- vices with changeable cuffs and has been expressed in mmHg. Hypertension has been observed in 159 chil- dren. They were divided into four groups. First group: non-Roma children (n = 32) with blood lead level of up to 10 mcg/dl. Second group: Roma children (n = 31) with blood lead level of up to 10 mcg/dl. Third group: Roma children (n = 53) with blood lead levels of 10-45 mcg/dl. Fourth group: Roma children (n = 43) with blood lead levels more than 45 mcg/dl, with an average value of 61.6 mcg/dl. Results: There is a statistically signifi- cant difference in the elevation of systolic blood pres- sure between group (chi-square = 31,179; p < 0,001), the first (x = 107,2 mmHg) and the fourth group (x = 114,6 mmHg), the second (x = 104,5 mmHg) and fou- rth group, third (x =106,4 mmHg) and fourth group. There is a statistically significant difference in the ele- vation of diastolic blood pressure between group (chi-square = 32,028; p < 0,001), the first (x = 67,7 mmHg) and the fourth group (x =73,4 mmHg), the sec- ond (x = 66 mmHg) and third group (x = 69 mmHg), second and fourth group, third and fourth group of chil- dren. It is concluded that when the value of lead in the blood was higher its effect on blood pressure was more pronounced. Conclusion: Most children with lead lev- els over 45 mcg/dl have developed an increased blood pressure as well, which required further observation and testing. Twelve of the children from the fourth gro- up have significant hypertension. But, none of the chil- dren have shown severe hypertension values.
Mid- and long-term outcome of 89 premature infants weighing less than 1,000 g at birth, all appropriate for gestational age.

OBJECTIVE Advances in obstetrical and neonatal care have achieved dramatic reductions in the mortality of extremely low birth weight infants, but concerns regarding the long-term neurodevelopmental prognosis have increased. The study was performed to assess the physical and developmental status of premature infants weighing < 1,000 g at birth who were appropriate for gestational age (AGA). METHODS A follow-up study including school level, physical and developmental examination and/or interviews of parents, pediatricians, teachers and social workers was carried out from January 1, 1981 to December 31, 1991, on 176 subjects who had been AGA premature neonates weighing < 1,000 g and were admitted to the Port Royal Neonatal Intensive Care Unit. Eighty-nine survived (50 girls, 39 boys). Five children were lost to follow-up after 3 years of age. Neurological sequelae, developmental and/or intellectual quotients, school level and results, vision, hearing, language, weight, height, and behavior were evaluated. RESULTS At the last evaluation, 37% of children were completely normal (24% had always been normal); 52% were normal in the 4th year of life, decreasing to 31% in the 8th year. Minor disabilities increased from 31% in the 4th year to 53% in the 8th year. Moderate disabilities ranged yearly between 8 and 14%. Five children had major handicaps diagnosed before 3 years of age (4 cerebral palsies following severe neonatal brain lesions and 1 severe retardation with renal dwarfism). No difference was found between children with or without bronchopulmonary dysplasia. Twelve children (14%) had hearing loss (3 deafness) and 27 (32%) had visual deficits (no blindness). Nursery school begins at 3 for French children: 86% of the followed survivors were at nursery school at 3 years of age, 74% of 6-year-olds were in the first grade, primary school, and 50% of 7-year-olds were in second grade. Half the children with high socioeconomic/cultural risks had some school difficulties. Similar results were collected from various cross-sectional studies in the recent literature. CONCLUSIONS While 20% of the children had moderate to severe disabilities, an increasing number of minor deficiencies appeared with age. Socio-economic/cultural factors had a deleterious effect even in structurally normal children, but they had an even worse effect in children with minor deficiencies, owing largely to the frequent lack of proper management at home.
Plasma ADAMTS-13 activity in proliferative lupus nephritis: a large cohort study from China

Objectives The aim of this study was to investigate plasma ADAMTS-13 activity in patients with proliferative lupus nephritis and to evaluate the role of clinical, laboratory and pathological features, especially the vascular lesions in lupus nephritis. Methods Plasma samples from 163 class III and IV lupus nephritis patients confirmed by biopsy examinations and 98 normal controls were collected. ADAMTS-13 activity was evaluated by a residual collagen binding assay. IgG autoantibodies against ADAMTS-13 were detected by ELISA using recombinant ADAMTS-13 as a solid-phase ligand. Levels of vWF were measured by ELISA. Their associations with clinical, laboratory and pathological features were further assessed. Results Plasma ADAMTS-13 activity in lupus nephritis patients was significantly lower than that in normal controls (84 ± 21% vs. 90 ± 13%, p = 0.005). IgG ADAMTS-13 autoantibodies were detected in only three patients. The plasma level of vWF was significantly higher in the lupus nephritis group than in normal controls (1.00 ± 0.79 vs. 0.70 ± 0.30, p = 0.025). Plasma ADAMTS-13 activity was negatively correlated with the level of serum creatinine and proteinuria (r = –0.354, p < 0.001; r = –0.200, p = 0.011, respectively). Patients with a higher level of ADAMTS-13 activity had significantly higher levels of factor H (401.51 ± 183.01 µg/ml vs. 239.02 ± 155.45 µg/ml, p = 0.005). Plasma ADAMTS-13 activity was negatively associated with total pathological AI scores (r = –0.326, p < 0.001), endocapillary hypercellularity (r = –0.419, p < 0.001), cellular crescents (r = –0.274, p < 0.001), subendothelial hyaline deposits (r = –0.266, p = 0.001), interstitial inflammatory cell infiltration (r = –0.304, P < 0.001), tubular atrophy (r = –0.199, p = 0.011), acute glomerular vascular lesions (r = –0.344, p < 0.001) and acute renal vascular lesions (r = –0.338, p < 0.001). No association was found between level of vWF and plasma ADAMTS-13 activity (r = 0.033, p = 0.671). Low level of ADAMTS-13 activity was a risk factor for renal outcomes (p = 0.039, HR = 0.047, 95% CI: 0.120–1.005). Conclusions Decreased ADAMTS-13 activity was found in patients with proliferative lupus nephritis, and plasma ADAMTS-13 activity was closely associated with renal injury indices, especially pathological vascular scores. The role of ADAMTS-13 in the disease remains to be further investigated.
Moving toward consensus on diagnosis and management of severe asthma in adults

Abstract Asthma is a considerable health problem with an increasing global prevalence. The burden of severe asthma is expected to notably increase in the following years. Some misleading concepts that sometimes appear in the literature can drive the physician responsible for a patient’s management to make incorrect decisions. Furthermore, some of the concepts that appear in the literature and in the guidelines may not be clear to understand, follow or adapt to regional and local realities. This could again drive the physicians responsible for a patient’s management to make incorrect clinical judgments. In this article, we review the definition, prevalence and immunopathology of severe asthma, describe the asthma phenotypes, clinical features and comorbidities, the diagnosis of severe asthma and personalized asthma treatment. At the end, we offer a treatment approach based on literature publications, personalized medicine and marketed biologic treatment options.
Compliant force control of robonaut contacting with the environment

This paper proposes a contact force control approach of Robonaut which can adjust the contact force between arm link and operation environment when the robot executing coordinated operation task. Firstly, the tightly coordinated operation model is established to analyze the constraints of motion and force between the end of robot arm and operation objects, and the internal force impedance control algorithm of operation objects is obtained. On this basis, we set up the contact model between arm linking and work environment, to study the mapping relationship of contact force controlling torque in the null space, and then the contact force control method is designed. Finally, the numerical simulation of Robonaut is carried out to verify the validity of the methods above.
Traumatic Brain Injury History Is Associated With an Earlier Age of Dementia Onset in Autopsy-Confirmed Alzheimer’s Disease

Objective: To evaluate whether a history of traumatic brain injury (TBI) with reported loss of consciousness (LOC) is a risk factor for earlier onset of Alzheimer’s disease (AD) in an autopsy-confirmed sample. Method: Data from 2,133 participants with autopsy-confirmed AD (i.e., at least Braak neurofibrillary tangle stages III to VI and CERAD neuritic plaque score moderate to frequent) were obtained from the National Alzheimer’s Coordinating Center (NACC). Participants were categorized by presence/absence of self-reported remote (i.e., >1 year prior to their first Alzheimer’s Disease Center visit) history of TBI with LOC (TBI+ vs. TBI−). Analyses of Covariance (ANCOVA) controlling for sex, education, and race compared groups on clinician-estimated age of symptom onset and age of diagnosis. Results: Average age of onset was 2.34 years earlier (p = .01) for the TBI+ group (n = 194) versus the TBI− group (n = 1900). Dementia was diagnosed on average 2.83 years earlier (p = .002) in the TBI+ group (n = 197) versus the TBI− group (n = 1936). Using more stringent neuropathological criteria (i.e., Braak stages V-VI and CERAD frequent), both age of AD onset and diagnosis were 3.6 years earlier in the TBI+ group (both p’s < .001). Conclusions: History of TBI with reported LOC appears to be a risk factor for earlier AD onset. This is the first study to use autopsy-confirmed cases, supporting previous investigations that used clinical criteria for the diagnosis of AD. Further investigation as to possible underlying mechanisms of association is needed.