Miracle-dz/UniFAR-FTUs huggingface dataset:
Frontotemporal Cortical Thinning in Amyotrophic Lateral Sclerosis

BACKGROUND AND PURPOSE: The extensive application of advanced MR imaging techniques has undoubtedly improved our knowledge of the pathophysiology of amyotrophic lateral sclerosis. Nevertheless, the precise extent of neurodegeneration throughout the central nervous system is not fully understood. In the present study, we assessed the spatial distribution of cortical damage in amyotrophic lateral sclerosis by using a cortical thickness measurement approach. MATERIALS AND METHODS: Surface-based morphometry was performed on 20 patients with amyotrophic lateral sclerosis and 18 age- and sex-matched healthy control participants. Clinical scores of disability and disease progression were correlated with measures of cortical thickness. RESULTS: The patients with amyotrophic lateral sclerosis showed a significant cortical thinning in multiple motor and extramotor cortical areas when compared with healthy control participants. Gray matter loss was significantly related to disease disability in the left lateral orbitofrontal cortex (P = .04), to disease duration in the right premotor cortex (P = .007), and to disease progression rate in the left parahippocampal cortex (P = .03). CONCLUSIONS: Cortical thinning of the motor cortex might reflect upper motor neuron impairment, whereas the extramotor involvement seems to be related to disease disability, progression, and duration. The cortical pattern of neurodegeneration depicted resembles what has already been described in frontotemporal dementia, thereby providing further structural evidence of a continuum between amyotrophic lateral sclerosis and frontotemporal dementia.
Prion (PrPC) expression in ovine uteroplacental tissues increases after estrogen treatment of ovariectomized ewes and during early pregnancy.

Scrapie in sheep is spread laterally by placental transmission of an infectious misfolded form (PrPSc) of a normal prion protein (PrPC) used as a template in PrPSc formation. We hypothesized that PrPC would be expressed in uterine and placental tissues and estradiol-17β (E2) would affect uterine PrPC expression. PrPC expression was evaluated in the uterus of long-term ovariectomized (OVX) ewes treated with an E2 implant for 2-24 h and in uteroplacental tissues from day 20 to day 30 of pregnancy. Expression of PrPC mRNA and PrPC protein increased in the uterus after E2 treatment of OVX ewes. In the maternal placenta, expression of PrPC mRNA and PrPC protein were unchanged, but in the fetal membranes (FM) PrPC mRNA and PrPC protein expression increased from day 20 to day 28. In the nonpregnant uterus, PrPC protein was immunolocalized at apical borders of the surface epithelium, in outer smooth muscle layers of large blood vessels, and in scattered stromal cells of the deep intercaruncular areas of the uterus. In the maternal placenta, PrPC protein was immunolocalized in the cytoplasm of flattened luminal epithelial cells apposed to the FM, whereas in the FM PrPC protein was in trophoblast cells and was also in several tissues of the developing embryo during early pregnancy. These data linking estrogen stimulation to increases in PrPC expression in uteroplacental tissues suggest that PrPC has a specific function during the estrous cycle and early pregnancy. Future studies should determine whether or not estrogen influences PrPC expression in other tissues, such as the nervous system and brain.
Mutations in PLOD2 cause autosomal‐recessive connective tissue disorders within the Bruck syndrome—Osteogenesis imperfecta phenotypic spectrum

PLOD2 and FKBP10 are genes mutated in Bruck syndrome (BS), a condition resembling osteogenesis imperfecta (OI), but that is also typically associated with congenital joint contractures. Herein, we sought mutations in six consanguineous BS families and detected changes in either PLOD2 or FKBP10 in all cases. Two probands were found with a homozygous frameshift mutation in the alternative exon 13a of PLOD2, indicating that specific inactivation of the longer protein isoform encoded by this gene is sufficient to cause BS. In addition, by homozygosity mapping, followed by a candidate gene approach, we identified a homozygous donor splice site mutation in PLOD2 in a patient with autosomal‐recessive OI (AR‐OI). Screening of additional samples also revealed compound heterozygous mutations in PLOD2 in two brothers, one affected with mild AR‐OI and the other with mild BS. Thus, PLOD2 in addition to causing BS is also associated with AR‐OI phenotypes of variable severity. Hum Mutat 33:1444–1449, 2012. © 2012 Wiley Periodicals, Inc.
Interferon therapy for chronic hepatitis C in habitual drinkers: comparison with chronic hepatitis C in infrequent drinkers.

OBJECTIVE To assess the efficacy of interferon therapy for chronic hepatitis C among habitual drinkers. METHODS Ninety-five hepatitis C virus ribonucleic acid-positive patients with chronic hepatitis were treated with four standardized regiments of interferon. Patients were divided into four groups based on the degree of daily alcohol consumption and duration of abstinence before treatment: 47 infrequent drinkers, 12 moderate drinkers who had consumed more than 23 gm but less than 69 gm of ethanol daily but stopped drinking for 39 +/- 18 months before therapy, 19 heavy drinkers I who had consumed more than 69 gm of ethanol daily but stopped drinking for 38 +/- 37 months before treatment, and 17 heavy drinkers II who consumed more than 69 gm ethanol daily soon before treatment. RESULTS The rate of responders; in whom serum ALT levels remained normal for 6 months after the end of treatment, was in a decreasing order of: infrequent drinkers (36.2%), moderate drinkers (33.3%), heavy drinkers I (26.3%), and heavy drinkers II (5.9%) (p < 0.05, infrequent drinkers vs heavy drinkers II). The negative rate of serum hepatitis C virus ribonucleic acid 6 months after the end of treatment was in a similar order (27.7%, 25.0%, 15.8%, and 0%, respectively) (p < 0.05, infrequent drinkers vs heavy drinkers II). CONCLUSION Heavy drinking will reduce the efficacy of interferon therapy for chronic hepatitis C, and the adverse effect of drinking on efficacy might be reversed, partly, by abstinence for a long period before treatment.
Donbas crisis key actors: narratives and perceptions in the interviews of Ukrainian elites

This article examines real events, their perceptions and narratives concerned with the key actors in the Donbas crisis – Ukraine, the EU/EU member states, Russia and the USA. Perceptions and narratives are traced in the texts of interviews with Ukrainian policy- and decision-makers from political, business, cultural, and civic cohorts (40 respondents). The elites were interviewed in the winter of 2016 within the framework of the Jean Monnet Network “Crisis, conflict and critical diplomacy: EU perceptions in Ukraine and Israel/Palestine” (C3EU), supported by Earsmus+ program of the European Commission. Informed by the strategic narrative theory [Miskimmon et al. 2013], the article undertakes a qualitative content analysis of the interview texts, explicating elite perceptions of the crisis in Donbas. The results spell the need for a more nuanced understanding of Ukraine’s perceptions of key actors in the ongoing conflict as well as the origin of these perceptions. Arguably, such understanding may benefit the EU’s critical diplomacy towards Ukraine and add a valuable insight to the constructive dialogue between Ukraine and the EU.
A multicenter, double-blind, randomized, placebo controlled trial of infliximab combined with low dose methotrexate in Japanese patients with rheumatoid arthritis.

OBJECTIVE A placebo controlled, double-blind trial (DBT) was conducted for Japanese patients with active rheumatoid arthritis (RA) despite treatment with low dose methotrexate (MTX) to evaluate the efficacy and safety of infliximab. Extended treatment with infliximab was conducted in an open-label trial (OLT). METHODS In the DBT, 147 patients were randomly assigned and treated with a placebo or 3 mg/kg or 10 mg/kg infliximab at Weeks 0, 2 and 6, combined with MTX. In the OLT, 129 patients from the DBT received 3 mg/kg infliximab every 8 weeks. RESULTS The mean dose of MTX was 7.2 +/- 2.0 mg/week. Significantly more patients receiving 3 mg/kg (61.2%) and 10 mg/kg (52.9%)infliximab achieved a 20% improvement according to the American College of Rheumatology (ACR) criteria at Week 14, compared to placebo (23.4%) (p < 0.001). There was no significant difference in incidence of adverse events among the treatment groups. In patients receiving infliximab in the DBT, 11.6% of patients with serum infliximab just before the OLT developed antibodies to infliximab (ATI) in the OLT, whereas 62.2% of patients without serum infliximab did. In patients receiving placebo in the DBT, 43.9% developed ATI. CONCLUSION The efficacy and safety of infliximab combined with low dose MTX were similar to those of the ATTRACT study. The data from the DBT and OLT also supported the importance of an induction treatment of infliximab, followed by a maintenance treatment without a long interval, giving stable serum concentrations in order to prevent formation of ATI.
Anti-hypothalamus and anti-pituitary antibodies may contribute to perpetuate the hypopituitarism in patients with Sheehan's syndrome.

OBJECTIVE While anti-pituitary antibodies (APAs) were detected in some patients with Sheehan's syndrome (SS) suggesting an autoimmune pituitary involvement in the development of their hypopituitarism, hypothalamic cell anti-hypothalamus antibodies (AHAs) have not been investigated so far. DESIGN The aim of this study was to evaluate the presence of AHA and APA in SS patients to verify whether an autoimmune hypothalamic-pituitary process can contribute to their late hypopituitarism. METHODS Twenty women with SS with a duration of disease ranging from 3 to 40 years (median 25.5 years) were enrolled into the study. Out of 20 patients, 12 (60%) had panhypopituitarism and the others had partial hypopituitarism well corrected with appropriate replacement therapy. None of them had clinical central diabetes insipidus. AHA and APA were investigated by immunofluorescence method in all patients. In addition, a four-layer immunofluorescence method was used to verify whether AHA immunostained vasopressin-secreting cells (AVP-c) or not. RESULTS AHAs were found in 8 out of 20 (40%) and APAs in 7 out of 20 (35%) patients with titers ranging from 1:32 to 1:128 and 1:16 to 1:32 respectively; however, in none of these positive patients AHA immunostained vasopressin cells. None of controls resulted positive for both antibodies. CONCLUSIONS Patients with SS, even many years after the onset of SS, can show antibodies to pituitary and/or hypothalamic but not AVP-secreting cells. Antibodies to unknown hypothalamic cells (releasing factor-secreting cells) other than APAs suggest that an autoimmune process involving both the hypothalamus and pituitary gland may contribute to late pituitary dysfunction in SS patients.
The glucose‐starvation stimulon of Escherichia coli: induced and repressed synthesis of enzymes of central metabolic pathways and role of acetyl phosphate in gene expression and starvation survival

Proteins of the glucose‐starvation stimulon were identified by using two‐dimensional gel electrophoresis and the gene–protein database of Escherichia coli. Members of this stimulon Included enzymes of the Embden–Meyerhof–Parnas (EMP) pathway, phosphotransacetylase (Pta) and acetate kinase (AckA) of the acetyl phosphate/acetate production pathway, and formate transacetytase. The synthesis of these enzymes was found to be Induced concomitantly with the decreased synthesis of enzymes of the Krebs cycle. Thus, the modulation in the synthesis of specific proteins during aerobic glucose starvation is, In part, similar to the response of cells shifted to anaerobiosis. These modulations suggest that the glucose‐starved cell increases the relative flow of carbon through the Pta–AckA pathway. Indeed, the ability to synthesize acetyl phosphate, an intermediate of the pathway, appears to be indispensable for glucose‐starved cells as pta and pta–ackA double mutants were found to be impaired in their ability to survive glucose starvation. The survival characteristics of ackA mutants and the wild‐type parent were indistinguishable. Moreover, the pta mutant failed to induce several proteins of the glucose‐starvation stimulon.
Can mortality of cancer patients with fever and neutropenia be improved?

Purpose of review Neutropenic fever is the most common infective complication in patients receiving cytotoxic chemotherapy, and may result in severe sepsis, septic shock and mortality. Advancements in approaches to empiric antimicrobial therapy and prophylaxis have resulted in improved outcomes. Mortality may, however, still be as high as 50% in high-risk cancer populations. The objective of this review is to summarize factors associated with reduced mortality in patients with neutropenic fever, highlighting components of clinical care with potential for inclusion in quality improvement programs. Recent findings Risks for mortality are multifactorial, and include patient, disease and treatment-related factors. Historically, guidelines for management of neutropenic fever have focused upon antimicrobial therapy. There is, however, a recognized need for early identification of sepsis to enable timely administration of antibiotic therapy and for this to be integrated with a whole of systems approach within healthcare facilities. Use of Systemic Inflammatory Response Syndrome criteria is beneficial, but validation is required in neutropenic fever populations. Summary In the context of emerging and increasing infections because of antimicrobial-resistant bacteria in patients with neutropenic fever, quality improvement initiatives to reduce mortality must encompass antimicrobial stewardship, early detection of sepsis, and use of valid tools for clinical assessment. C-reactive protein and procalcitonin hold potential for inclusion into clinical pathways for management of neutropenic fever.
Quantum Transport Simulation of Nanowire Resonant Tunneling Diodes Based on a Wigner Function Model With Spatially Dependent Effective Masses

We present a self-consistent and three-dimensional quantum simulation for nanowire resonant tunneling diodes (RTDs) based on the Wigner transport equation with spatially dependent effective masses (SDEM), which is discretized by a third-order upwind difference scheme for high-accuracy calculation. Our calculation shows that the current density/voltage (<inline-formula><tex-math notation="LaTeX">$J\text{--}V$</tex-math></inline-formula>) characteristics of nanowire RTDs with a radius (<inline-formula><tex-math notation="LaTeX">$R$</tex-math></inline-formula>) <inline-formula><tex-math notation="LaTeX">$<$</tex-math></inline-formula> 5 nm largely deviate from those of the one-dimensional RTDs. As <inline-formula><tex-math notation="LaTeX">$R$</tex-math></inline-formula> decreases below 5 nm, the peak-to-valley ratio (PVR) of the low-<inline-formula><tex-math notation="LaTeX">$V$</tex-math> </inline-formula> negative differential resistance (NDR) decreases rapidly, and the high-<inline-formula> <tex-math notation="LaTeX">$V$</tex-math></inline-formula> NDR peak shifts sensitively to lower <inline-formula> <tex-math notation="LaTeX">$V$</tex-math></inline-formula> and becomes sharper. In this study, these results are shown to be closely related to the SDEM. According to our analysis, the SDEM along the transport direction contributes to the formation of an ‘effective double barrier’ in the energy subbands that is higher than the double barrier expected by the band offset, and the SDEM along the confinement direction reduces the height of the effective double barrier. The performance of nanowire RTDs with <inline-formula><tex-math notation="LaTeX">$R<$</tex-math> </inline-formula> 5 nm was proven to be highly dependent on <inline-formula><tex-math notation="LaTeX">$R$ </tex-math></inline-formula> because of the SDEM along the confinement direction.
MiR‐21 regulates epithelial‐mesenchymal transition phenotype and hypoxia‐inducible factor‐1α expression in third‐sphere forming breast cancer stem cell‐like cells

Cancer stem cells (CSCs) are predicted to be critical drivers of tumor progression due to their “stemness”, but the molecular mechanism of CSCs in regulating metastasis remains to be elucidated. Epithelial‐mesenchymal transition (EMT), hypoxia‐inducible factor (HIF)‐1α, and miR‐21, all of which contribute to cell migration for metastasis, are interrelated with CSCs. In the present study, third‐sphere forming (3‐S) CSC‐like cells, which showed elevated CSC surface markers (ALDH1+ and CD44+/CD24−/low) and sphereforming capacity as well as migration and invasion capacities, were cultured and isolated from breast cancer MCF‐7 parental cells, to evaluate the role of miR‐21 in regulating the CSC‐like cell biological features, especially EMT. EMT, which was assessed by overexpression of mesenchymal cell markers (N‐cadherin, Vimentin, alpha‐smooth muscle actin [α‐SMA]) and suppression of epithelial cell marker (E‐cadherin), was induced in 3‐S CSC‐like cells. Moreover, both of HIF‐1α and miR‐21 were upregulated in the CSC‐like cells. Interestingly, antagonism of miR‐21 by antagomir led to reversal of EMT, downexpression of HIF‐1α, as well as suppression of invasion and migration, which indicates a key role of miR‐21 involved in regulate CSC‐associated features. In conclusion, we demonstrated that the formation of CSC‐like cells undergoing process of EMT‐like associated with overexpression of HIF‐1α, both of which are regulated by miR‐21. (Cancer Sci 2012; 103: 1058–1064)
High performance and cost effective memory architecture for an HDTV decoder LSI

This paper proposes an efficient memory mapping and a frame memory compression for an HDTV decoder LSI using Direct Rambus/sup TM/ DRAM (DRDRAM). The DRDRAM is employed to achieve the high memory bandwidth required for HDTV decoding at the minimum memory cost. The proposed memory mapping achieves a high memory bandwidth sufficient for HDTV decoding even in the worst case and no costly line buffers are required in the LSI for format conversion. The frame memory compression method reduces the memory cost by half and achieves HDTV decoding with a single 64 Mb DRDRAM chip without loss of memory access efficiency. Simulation results show that SNR degradation is 0.1 to 2 dB in the worst frame and no visible degradation is perceived except for a resolution chart sequence.
Pharmacokinetics of Oral Acyclovir in Neonates and in Infants: a Population Analysis

ABSTRACT Acyclovir is approved for the treatment of herpes simplex virus (HSV) and varicella-zoster virus (VZV) infections in children by the intravenous and oral routes. However, its use by the oral route in children younger than 2 years of age is limited due to a lack of pharmacokinetic data. The objectives of the present study were to determine the typical pharmacokinetics of an oral suspension of acyclovir given to children younger than 2 years of age and the interindividual variabilities in the values of the pharmacokinetic parameters in order to support the proposed dosing regimen (24 mg/kg of body weight three times a day for patients younger than 1 month of age or four times a day otherwise). Children younger than age 2 years with HSV or VZV infections were enrolled in a multicenter study. Children were treated for at least 5 days with an acyclovir oral suspension. Plasma samples were obtained at steady state, before acyclovir administration, and at 2, 3, 5, and 8 h after acyclovir administration. Acyclovir concentrations were measured by radioimmunoassay. The data were analyzed by a population approach. Data for 79 children were considered in the pharmacokinetic study (212 samples, 1 to 5 samples per patient). Acyclovir clearance was related to the estimated glomerular filtration rate, body surface area, and serum creatinine level. The volume of distribution was related to body weight. The elimination half-life decreased sharply during the first month after birth, from 10 to 15 h to 2.5 h. Bioavailability was 0.12. The interindividual variability was less pronounced when the parameters were normalized with respect to body weight. Hence, dosage adjustment by body weight is recommended for this population. Simulations showed that the length of time that acyclovir remains above the 50% inhibitory concentration during a 24-h period was more than 12 h for HSV but not for VZV. The proposed dosing regimen seems adequate for the treatment of HSV infections, while for the treatment of VZV infections, a twofold increase in the dose seems necessary for children older than age 3 months.
Clinical correlations of small bowel CT and contrast radiology findings in Crohn's disease.

BACKGROUNDS AND OBJECTIVE Aim of the present study was to evaluate the clinical correlates of small bowel CT patterns in patients with Crohn's disease (CD), as compared to barium studies and endoscopic findings, as far as parameters of disease activity are concerned. MATERIAL AND METHODS Thirty five patients with pathologically proven CD were studied by means of helical single detector CT (13) or multidetector CT (22), after administration of low density contrast by mouth (13) or by nasojeunal tube (22). Eight hours later, all patients were studied with barium administered by mouth (13) or with barium and methilcellulose administered by nasojeunal tube (22). Clinical activity was assessed by CDAI score, ESR, CRP, alpha1 glycoprotein and fibrinogen levels. In twenty one patients, colonoscopy was also performed. RESULTS Sensitivity of small bowel CT versus endoscopy was of 88% while sensitivity of barium studies was of 77% versus endoscopic findings, and it reached 100% for the combination of both exams. We found positive correlations between the detection at CT of "target sign" and a CDAI score > 150 or abnormal values of CRP, ESR, alpha1 glycoprotein. Abnormal ESR or fibrinogen levels were correlated with the detection of fistulas at CT scans. The diameter of enlarged mesenteric lymph nodes was correlated with alpha1 glycoprotein values. No similar correlations were detected for contrast radiology findings. DISCUSSION This study underscores the clinical usefulness of performing small bowel CT in adjunct to conventional diagnostic studies in Crohn's disease patients. CT findings (either by oral route or nasojeunal tube) correlate with parameters of disease activity.
Clinical approaches to osseous metastases in prostate cancer.

BACKGROUND Prostate cancer is unique among solid tumors in its proclivity to metastasize primarily to bone. Osseous metastases pose a formidable health threat to patients with metastatic disease, putting them at risk for pain, marrow crowding, fracture, and other sequelae. Treatments directed against bone disease have the potential both to palliate pain and to increase survival. CONCLUSIONS A number of agents exist that have the potential to palliate the effects of osseous metastases and should be routinely applied in the clinical care of the patient with advanced prostate cancer. These include hormones, bone-seeking radiopharmaceuticals, chemotherapy, and bisphosphonates. Strategies under investigation aim to eradicate bone disease, and not merely palliate symptoms. These approaches combine those listed above with tumor-directed targeting of osseous disease and manipulation of the biology that underlies the cancer's relationship to bone.