Miracle-dz/UniFAR-FTUs huggingface dataset:
Anatomic-Functional (Perfusion-Based) Magnetic Resonance Imaging Follow-up in Patients With Rheumatoid Arthritis Treated With Anti–Interleukin 6 Antibodies: A Comparison With Clinical Scores and Serologic Data

Objective On a 3-T magnetic resonance scanner, morphologic and perfusion changes of 9 patients with rheumatoid arthritis were evaluated after start of anti–interleukin 6 receptor antibody Tocilizumab (TCZ) treatment. Methods Morphologic and perfusion-based magnetic resonance imaging (MRI) parameters were assessed before and 4, 12, and 24 after the start of TCZ treatment. Furthermore, serologic biomarkers and clinical assessment scores were evaluated 4, 12, 24, and 52 weeks after treatment initiation. Results Results of MRI parameters showed significant group differences between responders and nonresponders for synovial volume, transfer constant, and blood plasma volume fraction already at week 12 as well as relative enhancement and rate of early enhancement at week 24. Conclusions Considering the temporal change of perfusion-derived MRI parameters (transfer constant, blood plasma volume fraction, relative enhancement, and rate of early enhancement) as well as morphologic MRI parameters (synovial volume measurements), a quantifiable assessment of response to TCZ therapy in rheumatoid arthritis seems possible at an even earlier time point compared with clinical assessment scores, whereas serologic biomarkers proved nonspecific in this respect.
Bacterial Endotoxin Induces Fos Immunoreactivity in Primary Afferent Neurons of the Vagus Nerve

Subdiaphragmatic vagotomy inhibits brain-mediated illness responses to peripherally administered bacterial endotoxin, including fever, hyperalgesia, sickness behavior, and activation of the hypothalamic-pituitary-adrenal axis. However, direct evidence implicating vagal afferents specifically in conveying information about peripheral immune activation to the brain is still lacking. This study assessed whether (1) endotoxin induces the expression of the functional activation marker Fos in the vagal sensory ganglia, and (2) vagotomy abrogates endotoxin-induced Fos expression in these ganglia. Male rats, which had previously received vagotomy or sham surgery, were injected intraperitoneally or intravenously with either endotoxin or saline. Fos immunolabeling was absent in saline-treated rats. In contrast, scattered cells within the vagal sensory ganglia showed Fos immunoreactivity after both intraperitoneal and intravenous endotoxin administration in sham-operated rats. Vagotomy abolished Fos expression after intraperitoneal endotoxin administration, whereas after intravenous administration Fos expression was strongly attenuated, but not eliminated. These findings implicate vagal afferents as a potential signaling pathway to brain regions that generate illness responses to pro-inflammatory mediators.
A New Developmentalism in Indonesia?

Abstract:Over the course of the past decade, Indonesia’s economic planning has become increasingly developmentalist in orientation. While aspects of this model have deep roots in the country’s history, a more self-conscious developmentalist agenda re-emerged during President Susilo Bambang Yudhoyono’s second term in office (2009–14). This paper suggests that under President Joko Widodo a new developmentalism has crystallized further and, arguably, become a defining feature of Indonesia’s political economy. To advance this argument, the paper draws upon studies of the “new developmentalism” in middle-income and emerging economies. This new developmentalism is characterized by a normative commitment to an activist state that can engineer fast economic growth, direct industrial upgrading, and ensure economic redistribution. However, developmental agendas should be distinguished from developmental outcomes. For Indonesia, state-led programmes for industrialization and inclusive economic growth have often fallen short. This study highlights some structural constraints upon the new developmentalism, with a particular focus upon politics. Specifically, it identifies patronage and clientelism as fundamental challenges to an effective state-led developmental model. Successive Indonesian governments, Jokowi’s included, have taken a conservative approach to the political problems that undermine their developmental goals.
Acetyl-L-carnitine: from a biological curiosity to a drug for the peripheral nervous system and beyond

Acetyl-L-carnitine (ALC) is a molecule derived from acetylation of carnitine in the mitochondria. Carnitine acetylation enables the function of CoA and facilitates elimination of oxidative products. Beyond this metabolic activity, ALC provides acetyl groups for acetylcholine synthesis, exerts a cholinergic effect and optimizes the balance of energy processes. Acetylcarnitine supplementation induces neuroprotective, neurotrophic and analgesic effects in the peripheral nervous system. In the recent studies, ALC, by acting as a donor of acetyl groups to NF-kb p65/RelA, enhanced the transcription of the GRM2 gene encoding the mGLU2 receptors, inducing long-term upregulation of the mGluR2, evidencing therefore that its long-term analgesic effects are dependent on epigenetic modifications. Several studies, including double-blind, placebo-controlled, parallel group studies and few open studies showed the effect of ALC in diseases characterized by neuropathies and neuropathic pain: the studies included diabetic neuropathy, HIV and antiretroviral therapy–induced neuropathies, neuropathies due to compression and chemotherapeutic agents. Double-blinded studies involved 1773 patients. Statistical evaluations evidenced reduction of pain, improvements of nerve function and trophism. In conclusion, ALC represents a consistent therapeutic option for peripheral neuropathies, and its complex effects, neurotrophic and analgesic, based on epigenetic mechanism, open new pathways in the study of peripheral nerve disease management.
Screening for acromegaly in adult patients not reporting enlargement of the extremities, but with arterial hypertension associated with another comorbidity of the disease.

OBJECTIVE To determine the value of acromegaly screening in adult patients not reporting enlargement of the extremities, but who present arterial hypertension associated with at least one other comorbidity of the disease. SUBJECTS AND METHODS Patients seen by general practitioners at primary health care units were evaluated. Among the patients without extremity enlargement, those with recently diagnosed arterial hypertension associated with at least one other comorbidity were selected. RESULTS A total of 1,209 patients were submitted to laboratory investigation. Elevated IGF-1 was observed in 22 patients. Eighteen patients had adequate suppression of growth hormone (GH). No GH suppression was observed in four women with confirmed elevated IGF-1. In the latter, IGF-1 and nadir GH were only slightly elevated, magnetic resonance showed a normal pituitary, and chest and abdominal computed tomography revealed no tumor, and no intervention was performed. CONCLUSION In patients with arterial hypertension without known pituitary disease, acromegaly is unlikely in the absence of enlargement of the extremities.
Grouping tourist complaints: what are inbound visitors’ problems with Chinese destinations?

ABSTRACT This study aims to examine inbound tourists’ complaints when visiting China and how these complaints differ in terms of tourist demographics. Tourists’ spontaneous reviews on TripAdvisor were analysed through manual coding and online automated software. Seven categories of complaint attributes with seventy-eight specific items were identified. The results showed different relationships between tourists’ demographic characteristics (age, gender, origins and travel pattern) and complaint items. The theoretical and practical implications of the study are discussed with regard to Chinese tourism management as well as future research.
Assessment of obesity and abdominal obesity among Portuguese children.

BACKGROUND Childhood obesity is a major public health issue in developed countries, and frequently proceeds into adulthood. The aim of this study was to estimate the prevalence of obesity and abdominal fat distribution in 6-12 years old children from the central region of Portugal, providing new data about trends on prevalence, epidemiology and evolution in obesity. METHODS Weight, height and waist circumference were measured in a random representative sample of 1,433 children (747 girls and 686 boys) from public schools in 2011. International Obesity Task Force (IOTF) cut-offs were used to define overweight and obesity. Abdominal obesity was estimated using the sex and age-specific = 90th waist circumference percentile and waist-to-height ratio cut-off. RESULTS The prevalence of overweight and obesity among children was 33.0%; 10.7% were obese. Overweight was significantly higher in boys than in girls (p = 0.044), whereas no gender differences was found in obesity (10.6 % in boys and 10.7% in girls, p = 0.571). The prevalence of abdominal obesity based on waist circumference was similar in girls and boys (3.8% vs. 3.9% respectively; p = 0.924), but significantly higher in boys than in girls based on waist-to-height ratio (28.1% vs. 19.4%, respectively; p = 0.009). Comparison with previous studies showed a slightly increase in overweight/obesity in children of central Portugal in the last 10 years, reaching values of 40.0% prevalence in the 7-9 years old. CONCLUSION In conclusion, this study shows a very high prevalence of overweight/obesity and abdominal obesity among Portuguese children, following the trend of other southern European countries. Thus, it is of the utmost importance the development of preventive and treatment strategies.
Comparison of the gating behaviour of human and murine cystic fibrosis transmembrane conductance regulator Cl− channels expressed in mammalian cells

1 To investigate the function of the murine cystic fibrosis transmembrane conductance regulator (CFTR), a full‐length cDNA encoding wild‐type murine CFTR was assembled and stably expressed in Chinese hamster ovary (CHO) cells. 2 Like human CFTR, murine CFTR formed Cl− channels that were regulated by cAMP‐dependent phosphorylation and intracellular ATP. However, murine CFTR Cl− channels had a reduced single‐channel conductance and decreased open probability (Po) compared with those of human CFTR. 3 Analysis of the dwell time distributions of single channels suggested that the reduced Po of murine CFTR was caused by both decreased residence in the open state and transitions to a new closed state, described by an intermediate closed time constant. 4 For both human and murine CFTR, ATP and ADP regulated the rate of exit from the long‐lived closed state. 5 5′‐Adenylylimidodiphosphate (AMP‐PNP) and pyrophosphate, two compounds that disrupt cycles of ATP hydrolysis, stabilized the open state of human CFTR. However, neither agent locked murine CFTR Cl− channels open, although AMP‐PNP increased the Po of murine CFTR. 6 The data indicate that although human and murine CFTR have many properties in common, some important differences in function are observed. These differences could be exploited in future studies to provide new understanding about CFTR.
Informed Trading in the WTI Oil Futures Market

The weekly release of the U.S. inventory level by the DOE-EIA is known as the market mover in the U.S. oil futures market. We uncover suspicious trading patterns in the WTI futures markets in days when the inventory level is released that are higher than market forecasts: there are significantly more orders initiated by buyers in the two hours preceding the official release of the inventory level, with a drop in the average price of -0.25% ahead of the news release. This finding is consistent with informed trading. We also provide evidence of an asymmetric response of the oil price to oil-inventory news, and highlight an over-reaction that is partly compensated in the hours following the announcement.
Searching for Autonomy in Digital News Entrepreneurism Projects

Abstract Digital entrepreneurism is often depicted as a positive disruption in the news ecosystem; it initiates new business models, fosters new ways of storytelling, and enables closer interaction with audiences. The extent to which entrepreneurial journalism entails a disruption of journalistic norms, roles, and procedures remains a matter of debate. Against this background, our study aims to explore how news entrepreneurism impacts journalistic autonomy on an organizational as well as an individual level. Conceptually, we define four dimensions of journalistic autonomy, namely organizational and procedural autonomy, as well as autonomy regarding professional norms and external influences such as funding and audiences. Empirically, we conducted interviews with founders of and journalists at 12 news startups in Germany. Our results indicate that both groups perceive a high level of autonomy in relation to professional norms and working procedures, and experience only little pressure from external influences. Still, the struggle for solid financing as well as the duality of economic and editorial duties limit both founders’ and journalists’ autonomy.
Characterisation of Urogenital Ridge Gene Expression in the Human Embryonal Carcinoma Cell Line NT2/D1

The study of the mammalian sex-determining pathway has been hampered by the lack of cell culture systems to investigate the underlying molecular relationships between sex-determining genes. Recent approaches using high-throughput genome-wide studies have revealed a number of sexually dimorphic genes expressed in the developing mouse gonad. Here, we investigated a human testicular cell line in terms of its expression of known sex-determining genes and newly identified candidates. The human embryonal carcinoma cell line NT2/D1 was screened for the expression of 46 genes with known or potential roles in the sex-determining and differentiation pathway. Forty genes tested were expressed in NT2/D1 cells including the testis-determining genes SRY, SOX9, SF-1, DHH and FGF9. Genes not expressed included WT1, DAX1 and the ovary-specific genes FOXL2 and WNT4. Cell-specific markers demonstrate that NT2/D1 cells reflect a number of cell types in the gonad including Sertoli, Leydig and germ cells. Our results suggest that male pathways initiated by SRY, SOX9 and SF-1 remain intact in these cells. Lack of expression of ovary-specific genes is consistent with a commitment of these cells to the male lineage. Manipulation of gene expression in this cell line could be an important new in vitro tool for the discovery of new human sex-determining genes.
BIRTH, MORPHOLOGIC, AND BLOOD CHARACTERISTICS OF FREE-RANGING WHITE-TAILED DEER NEONATES

Winter severity is a primary factor influencing deer survival and reproduction in northern climates. Prolonged, harsh winters can adversely affect body condition of does, resulting in depressed morphologic development of neonates. In this study, we captured 59 white-tailed deer (Odocoileus virginianus) neonates (28 in 2001 and 31 in 2002), following two distinctly different winters, one severe and the other historically mild. Vaginal implant transmitters allowed exact age to be determined for 73% of the neonates; new hoof growth was used to estimate age (days) of the other 27%. Birthdate and morphologic measurements of neonates (i.e., birth mass, new hoof growth, hoof length) were compared by sex and capture year. For known-age neonates (n=43), there was a year-by-sex interaction effect (P=0.01) on birthdate, being later for females during spring 2001 compared with 2002, which was consistent with a significant (P=0.03) year-by-sex interaction for total hoof length (22.3 mm [SE=0.9] and 20.3 [SE=0.8] for females and males in 2001; 19.9 [SE=1.0] and 22.1 [SE=1.0] for females and males in 2002). Interestingly, there was no effect of year on birth mass or birthdate of known-age neonates. A year-by-sex interaction (P=0.04) was determined for birthdates of estimated age (≤ days) neonates (n=16), with females born earlier than males in 2001 and later than males in 2002. Dam age had an apparent effect on birthdates of known-age neonates, as fawns born to dams ≤5 yr old were born later (P=0.01) than fawns born to dams >5 yr old (2 June and 26 May, respectively). Capture year had little effect on 20 hematologic and serum characteristics examined; however, there were significant (P<0.05) sex effects on red blood cell (RBC) counts, serum cholesterol, and cortisol concentrations, and a year-by-sex effect (P=0.04) on triglycerides. Mean corpuscular volume (MCV) was the only blood characteristic that differed (P<0.01) between years, with higher values occurring in spring 2001. We report a range of reference values for blood constituents that have not been previously documented for free-ranging neonates. Overall, winter severity appeared to have little effect on birth, morphologic, or blood characteristics of neonates. Documenting reference values for free-ranging, known-age neonates is of particular importance to enhancing our understanding of their rapid physiologic development, the concomitant changes in mean values of their blood constituents, and the natural variability that appears to be associated with those values. Our findings suggest caution should be exercised when applying physiologic models derived in captivity to free-ranging deer populations.
Prevention of cardiac disease by subcutaneous deferoxamine in patients with thalassemia major.

We examined the efficacy of long-term subcutaneous deferoxamine therapy in the prevention of iron-related cardiac disease in patients with thalassemia major who began treatment after the age of 10 years. Of 36 such patients without preexisting cardiac disease, 19 did not comply with the program of chelation therapy. Over the course of treatment (1977 to 1983) serum ferritin and aspartate aminotransferase levels fell in the compliant group, from mean values (+/- S.D.) of 4765 +/- 2610 to 2950 +/- 1850 ng per milliliter and 58.1 +/- 22 IU to 30 +/- 20 IU per liter, respectively (P less than 0.05), but rose in the noncompliant group, from 5000 +/- 2316 to 6040 +/- 2550 ng per milliliter and 56.6 +/- 20 to 90 +/- 35 IU per liter, respectively. Only one patient in the compliant group acquired cardiac disease and died of fulminant congestive heart failure. In contrast, 12 noncompliant patients acquired cardiac disease, and 7 died. In addition, the mean age of the compliant population (18.9 +/- 4.5 years) now approaches the mean age of acquisition of cardiac disease in the noncompliant group (19 +/- 4.3). These data demonstrate that compliance with treatment with deferoxamine may protect patients from cardiac disease induced by iron overload.
Esthetic evaluation of single-tooth implants in the anterior maxilla following autologous bone augmentation.

OBJECTIVES Autologous bone augmentation to rebuild compromised alveolar ridge contour prior to implant placement allows for favorable three-dimensional implant positioning to achieve optimum implant esthetics. The aim of the present study was to evaluate peri-implant soft tissue conditions around single-tooth implants following bone grafts in the esthetic zone of the maxilla. MATERIALS AND METHODS Sixty patients underwent autologous bone augmentation of deficient maxillary sites prior to placement of 85 implants in the esthetic zone. In case of multiple implants per patient, one implant was randomly selected. Objective evaluation of 60 single-tooth implants was performed using the Pink-Esthetic-Score (PES) and Papilla Index (PI) and supplemented by subjective patient evaluation, as well as clinical and radiologic examination. RESULTS Objective ratings of implant esthetics were satisfactory (median PES: 11, median PI: 2) and significantly correlated with high patient satisfaction (mean VAS score: 80%). Both esthetic indices demonstrated respectable levels of inter- as well as intra-observer agreement. Poor implant esthetics (low PES and PI ratings) were significantly associated with increased anatomic crown height, while no influence of horizontal implant-tooth distance could be found. CONCLUSIONS The present investigation indicates that favorable esthetic results may be achieved in the augmented anterior maxilla. However, bony reconstruction of compromised alveolar ridges does not guarantee optimum implant esthetics.
Molecular Insights into Quorum Sensing in the Human Pathogen Pseudomonas aeruginosa from the Structure of the Virulence Regulator LasR Bound to Its Autoinducer*

Many Gram-negative bacteria communicate via molecules called autoinducers to coordinate the activities of their populations. Such communication is termed quorum sensing and can regulate pathogenic virulence factor production and antimicrobial resistance. The quorum sensing system of Pseudomonas aeruginosa is currently the most intensively researched, because this bacterium is an opportunistic human pathogen annually responsible for the death of thousands of cystic fibrosis sufferers and many other immunocompromised individuals. Quorum sensing inhibitors can attenuate the pathogenicity of P. aeruginosa. Here we present the crystal structure of the P. aeruginosa LasR ligand-binding domain bound to its autoinducer 3-oxo-C12-acylhomoserine lactone. The structure is a symmetrical dimer, with each monomer exhibiting an α-β-α fold similar to the TraR and SdiA quorum sensing proteins of Agrobacterium tumefaciens and Escherichia coli. The structure was determined up to 1.8-Å resolution and reveals the atomic interactions between LasR and its autoinducer. The monomer structures of LasR, TraR, and SdiA are comparable but display differences in their quaternary organization. Inspection of their binding sites shows some unexpected variations resulting in quite different conformations of their bound autoinducers. We modeled interactions between LasR and various quorum sensing inhibitors, yielding insight into their possible mechanisms of action. The structure also provides a platform for the optimization, or de novo design, of quorum sensing inhibitors.
Selective specification of CNS stem cells into oligodendroglial or neuronal cell lineage: Cell culture and transplant studies

Neural stem cells (NSCs) were isolated from embryonic day 16 Sprague–Dawley rats and cultured in a novel serum‐free stem cell medium that selected for the growth of NSCs and against the growth of GFAP+ cells (astrocytes). NSCs maintained in culture for extended periods of time retained immunoreactivity for both nestin and PSA‐NCAM, two markers characteristic of the stem cell phenotype. Moreover, using an oligodendrocyte (OL) specification medium, NSCs differentiated into OL as evidenced by their morphology and expression of multiple oligodendrocyte/myelin‐specific markers. In addition, NSCs are capable of acquiring a neuronal phenotype as evidenced by expressing neuronal markers, such as neurofilament (NF) and NeuN when cultured in a defined medium for neurons indicating that these cells are also a good source of neuroblasts, which could be used to replace neuronal populations in the brain. We also showed successful propagation and differentiation of NSCs into OL after cryostorage, allowing for the later use of stored NSCs. The long‐term goal of culturing NSCs and committed oligodendrocyte progenitors (OLP) is to obtain homogeneous populations for transplantation with the goal of remyelinating the myelin‐deficient CNS. Our preliminary experiments carried out on normal and myelin deficient rats demonstrate that these cells survive and migrate extensively in both types of hosts. NSCs grafted as such, as well as cells derived from NSCs exposed to selective specification before grafting, are able to differentiate within the host brain. As expected, NSCs are capable of giving rise to astrocytes in a medium favoring this phenotype. © 2002 Wiley‐Liss, Inc.