Miracle-dz/UniFAR-FTUs huggingface dataset:
Fully 4D image reconstruction by estimation of an input function and spectral coefficients

A new dynamic image reconstruction method for PET is proposed. First, a set of exponential temporal basis functions is predefined, covering the entire range of kinetics (from static through to a delta function). Just as in spectral analysis, such a selection is designed to be able to handle all possible tissue responses for multi-compartmental tissue models. Second, an initial estimate of an input function is defined. The time-dependent PET radiotracer concentration is then modeled (through the system matrix in the reconstruction algorithm) as a superposition of the exponential temporal basis functions, convolved with the input function. The reconstruction method uses an expectation maximization (EM) algorithm to operate directly on the measured PET data in order to i. estimate the coefficients of the exponential functions, and ii. improve the estimate of the input function. The coefficients and the input function are estimated only as a means of regularizing the model of the time-dependent image: the final reconstruction is used with conventional post-reconstruction kinetic analysis, with a different input function if need be (as the estimated input function may not correspond to the true input function). Results from tests on simulated data reveal a simultaneous benefit of noise reduction and improved kinetic parameter estimates when compared to conventional methodology. The method is also demonstrated on measured HRRT PET data for an FDG study.
Identification of calcium binding sites that regulate potentiation of a neuronal nicotinic acetylcholine receptor.

The divalent cation calcium potentiates the physiological response of neuronal nicotinic receptors to agonists by enhancing ionic current amplitudes, apparent agonist affinity and cooperativity. Here we show that mutations in several consensus Ca2+ binding sequences from the N‐terminal domain of the neuronal alpha 7 nicotinic acetylcholine receptor alter Ca2+ potentiation of the alpha 7‐V201–5HT3 chimera. Mutations E18Q or E44Q abolish calcium‐enhanced agonist affinity but preserve the calcium increase of plateau current amplitudes and cooperativity. On the other hand, mutations of amino acids belonging to the 12 amino acid canonical domain (alpha 7 161–172) alter all features of potentiation by enhancing (D163, S169), reducing (E161, S165, Y167) or abolishing (E172) calcium effects on ionic current amplitudes and agonist affinity. Introduction of the alpha 7 161–172 domain in the calcium insensitive 5‐hydroxytryptamine (5HT3) serotoninergic receptor results in a receptor activated by 5HT and potentiated by calcium. In vitro terbium fluorescence studies with an alpha 7 160–174 peptide further show that mutation E172Q also alters in vitro calcium binding. Data are consistent with the occurrence of distinct categories of regulatory calcium binding sites, among which the highly conserved (alpha 7 161–172) domain may simultaneously contribute to calcium and agonist binding.
Determination of the knowledge of e-waste disposal impacts on the environment among different gender and age groups in China, Laos, and Thailand

E-waste is the fastest growing waste in the solid waste stream in the urban environment. It has become a widely recognised social and environmental problem; therefore, proper management is vital to protecting the fragile environment from its improper disposal. Questionnaire surveys were conducted to determine the knowledge of environmental impacts of e-waste disposal as it relates to mobile phones among different gender and age groups in China, Laos, and Thailand. The results revealed that gender was positively correlated with their knowledge of the status of environmental conditions (P104) (r = 0.077, n = 1994, p < 0.01) and negatively correlated with their knowledge of how to improve environmental conditions (P105) (r = –0.067, n = 2037, p < 0.01). In addition, an increase in age was positively correlated with respondents’ concern over the environmental conditions (P103) (r = 0.052, n = 2077, p < 0.05) and P105 (r = 0.061, n = 2061, p < 0.01) mentioned above. The results indicated that female respondents were less knowledgeable about how to improve environmental conditions than male respondents in the three countries. Knowledge gaps were detected in the respondents, at age ⩽17, in the three countries, and from age 18–22 to 36–45 or older from Thailand and China, on their knowledge of the existing e-waste-related laws. Thus, an effort to bridge the gaps through initiating proper educational programmes in these two countries is necessary.
Guidelines for the Management of Extremely Premature Deliveries: A Systematic Review

BACKGROUND AND OBJECTIVES: Available data on survival rates and outcomes of extremely low gestational age (GA) infants (22–25 weeks’ gestation) display wide variation by country. Whether similar variation is found in statements by national professional bodies is unknown. The objectives were to perform a systematic review of management from scientific and professional organizations for delivery room care of extremely low GA infants. METHODS: We searched Embase, PubMed, and Google Scholar for management guidelines on perinatal care. Countries were included if rated by the United Nations Development Programme’s Human Development Index as “very highly developed. ” The primary outcome was rating of recommendations from “comfort care” to “active care. ” Secondary outcomes were specifying country-specific survival and considering potential for 3 biases: limitations of GA assessment; bias from different definitions of stillbirths and live births; and bias from the use of different denominators to calculate survival. RESULTS: Of 47 highly developed countries, 34 guidelines from 23 countries and 4 international groups were identified. Of these, 3 did not state management recommendations. Of the remaining 31 guidelines, 21 (68%) supported comfort care at 22 weeks’ gestation, and 20 (65%) supported active care at 25 weeks’ gestation. Between 23 and 24 weeks’ gestation, much greater variation was seen. Seventeen guidelines cited national survival rates. Few guidelines discussed potential biases: limitations in GA (n = 17); definition bias (n = 3); and denominator bias (n = 7). CONCLUSIONS: Although there is a wide variation in recommendations (especially between 23 and 24 weeks’ GA), there is general agreement for comfort care at 22 weeks’ GA and active care at 25 weeks’ GA.
Expression of the multidrug resistance‐associated protein (MRP) mRNA and protein in normal peripheral blood and bone marrow haemopoietic cells

We studied the expression of multidrug resistance‐associated protein (MRP) in normal haemopoietic cells from peripheral blood and bone marrow. The MRP mRNA levels were estimated by RT/PCR and in situ hybridization (ISH) assay, and the protein levels by flow cytometry. 21 samples of peripheral blood and 21 samples of bone marrow (11 normal bone marrow donors, 10 patients in complete remission after chemotherapy for large cell lymphoma or acute myeloid leukaemia) were analysed. In peripheral blood the mean MRP mRNA level in CD3+ cells was statistically higher than in the other cells (3‐fold by the methods used). The levels of MRP in CD3+ varied from one individual to another (4.5–34.8 units by RT/PCR and 5–23 grains/cell by ISH); however, this was proportional to the variation in all the cell lineages of same individual (r = 0.84). In bone marrow the mean MRP levels of the various cell lineages (including CD34+) were similar to the basal level in HL60 cells. Individual expression levels were again variable; however, there was no difference between untreated normal bone marrow and post chemotherapy normal bone marrow. MRP protein expression was determined by flow cytometry with the monoclonal antibody MRPm6. The CD4+ lymphocytes exhibited a higher MRP protein expression than the other cell lineages, including CD8+ cells. There was a good correlation between the three methods used (RT/PCR and ISH, P = 0.0001, r = 0.87; RT/PCR and flow cytometry, P = 0.0001, r = 0.85; ISH and flow cytometry, P = 0.002, r = 0.67).
ACL Graft and Contralateral ACL Tear Risk within Ten Years Following Reconstruction: A Systematic Review

Background:Anterior cruciate ligament (ACL) graft tear and contralateral ACL injury have devastating effects on patient outcomes following ACL reconstruction. Long-term results after ACL reconstruction are being reported with greater frequency, allowing a detailed analysis of the long-term risk of failure. Methods:A systematic review of prospective studies that recorded the risk of ACL graft rupture and contralateral ACL injury following primary ACL reconstruction was performed. All studies included intra-articular ACL reconstruction with modern techniques and patellar tendon or hamstring autograft with a minimum follow-up of ten years. Results:Nine studies met the inclusion and exclusion criteria. The overall ACL graft rupture risk was 7.9% (211 ruptures in 2682 reconstructions) and ranged from 3.2% to 11.1% in the individual studies. The overall risk of ACL injury in the contralateral limb was 12.5% (335 injuries in 2682 reconstructions) and ranged from 0.6% to 22.7% in the individual studies. Among the seven homogeneous studies that were pooled, the overall risk of a contralateral ACL tear was 1.63 (95% confidence interval [CI]: 1.30 to 2.04) times that of a graft tear during the follow-up period. Conclusions:At a minimum follow-up time of ten years, the risk of contralateral ACL tear significantly exceeds the risk of ACL graft rupture. Further work is necessary to understand and potentially reduce this risk of graft and contralateral ACL tears. Level of Evidence:Therapeutic Level II. See Instructions for Authors for a complete description of levels of evidence.
Abnormal ratio of membrane immunoglobulin classes in mice with an X- linked B-lymphocyte defect

CBA/N mice have an X-linked genetic defect in B-lymphocyte function manifested by inability to make antibody responses to T-independent antigens. Plasma membrane immunoglobulin (Ig) on spleen, lymph node, and Peyer's patch cells was analyzed by lactoperoxidase-catalyzed iodination, NP-40 extraction, specific immunoprecipitation, and sodium dodecyl sulfate-polyacrylamide gel electrophoresis. These studies indicated that the X-linked immune defect was associated, in all three cell types, with a decrease in the ratio of cell membrane IgD analog to cell membrane IgM. This suggests either that IgD analog may be important in initiation of T-independent antibody responses or that CBA/N mice lack a subpopulation of B cells specialized to respond to T- independent antigens, and that these cells are relatively rich in plasma membrane IgD analog.
Are Employers Changing Their Behavior Toward Older Workers? An Analysis of Employers' Surveys 2000–2009

This article addresses possible changes in Dutch employers' behavior regarding the recruitment and retention of older workers during the last decade. The authors analyze surveys administered to Dutch employers in 2000, 2002, 2005, 2008, and 2009. The results show that efforts to recruit older workers are changing, congruous with the economic climate, while retention behavior shows a clear and rather gradual time effect. The authors conclude that the position of older workers has improved between 2000 and 2008 and has done so in comparison with other underrepresented groups in the labor market. During the recession, recruitment of older workers declined substantially, while efforts to retain older workers are in both absolute and relative terms higher than in 2000. With respect to organizational policies, the authors conclude that throughout the period under observation these policies are dominated by measures that “spare” older workers.
Three-dimensional characteristics of neck movements in subjects with mechanical neck disorder.

STUDY DESIGN Controlled laboratory study. OBJECTIVES To examine characteristics of neck movement at three-dimensional planes for subjects with mechanical neck disorder (MND) and measure cervical range of motion, coupling motion, and calculation of the upper cervical rotation ratio. BACKGROUND MND is characterized by symptoms of neck pain, headache, dizziness and limited range of motion (ROM). However, the characteristics of neck movements across the three-dimensional planes in MND patients remain unknown. METHODS Forty participants were recruited, which consisted of twenty-seven subjects with MND and 13 healthy subjects. A three-dimensional electromagnetic motion capture device with custom data analysis software was used to measure the neutral position of the neck and the range of motion of upper and lower cervical spine. RESULTS The results indicate that subjects with MND had significantly decreased ROM in right rotation (p< 0.05) and extension (p< 0.05) movements compared to the healthy group. Increased coupling motion (p< 0.05) in the rotation plane during cervical flexion was also found in the MND group compared to control group. For rotations in neutral or in flexion positions, rotation to the right showed smaller range of motion compared to rotation to the left. CONCLUSION In this study, MND was associated with altered cervical movement patterns with increases in coupling motion. The findings may help to differentiate MND from whiplash-associated disorder. Increasing upper cervical spine rotation mobility may be crucial for treating deficiencies in neck rotation in patients with MND.
Gene expression profile of A549 cells from tissue of 4D model predicts poor prognosis in lung cancer patients

The tumor microenvironment plays an important role in regulating cell growth and metastasis. Recently, we developed an ex vivo lung cancer model (four dimensional, 4D) that forms perfusable tumor nodules on a lung matrix that mimics human lung cancer histopathology and protease secretion pattern. We compared the gene expression profile (Human OneArray v5 chip) of A549 cells, a human lung cancer cell line, grown in a petri dish (two‐dimensional, 2D), and of the same cells grown in the matrix of our ex vivo model (4D). Furthermore, we obtained gene expression data of A549 cells grown in a petri dish (2D) and matrigel (three‐dimensional, 3D) from a previous study and compared the 3D expression profile with that of 4D. Expression array analysis showed 2,954 genes differentially expressed between 2D and 4D. Gene ontology (GO) analysis showed upregulation of several genes associated with extracellular matrix, polarity and cell fate and development. Moreover, expression array analysis of 2D vs. 3D showed 1,006 genes that were most differentially expressed, with only 36 genes (4%) having similar expression patterns as observed between 2D and 4D. Finally, the differential gene expression signature of 4D cells (vs. 2D) correlated significantly with poor survival in patients with lung cancer (n = 1,492), while the expression signature of 3D vs. 2D correlated with better survival in lung cancer patients with lung cancer. As patients with larger tumors have a worse rate of survival, the ex vivo 4D model may be a good mimic of natural progression of tumor growth in lung cancer patients.
Alternative Approaches for Efficient Inhibition of Hepatitis C Virus RNA Replication by Small Interfering RNAs

ABSTRACT Persistent infection with hepatitis C virus (HCV) is a leading cause of chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma. It has recently been shown that HCV RNA replication is susceptible to small interfering RNAs (siRNAs), but the antiviral activity of siRNAs depends very much on their complementarity to the target sequence. Thus, the high degree of sequence diversity between different HCV genotypes and the rapid evolution of new quasispecies is a major problem in the development of siRNA-based gene therapies. For this study, we developed two alternative strategies to overcome these obstacles. In one approach, we used endoribonuclease-prepared siRNAs (esiRNAs) to simultaneously target multiple sites of the viral genome. We show that esiRNAs directed against various regions of the HCV coding sequence as well as the 5′ nontranslated region (5′ NTR) efficiently block the replication of subgenomic and genomic HCV replicons. In an alternative approach, we generated pseudotyped retroviruses encoding short hairpin RNAs (shRNAs). A total of 12 shRNAs, most of them targeting highly conserved sequence motifs within the 5′ NTR or the early core coding region, were analyzed for their antiviral activities. After the transduction of Huh-7 cells containing a subgenomic HCV replicon, we found that all shRNAs targeting sequences in domain IV or nearby coding sequences blocked viral replication. In contrast, only one of seven shRNAs targeting sequences in domain II or III had a similar degree of antiviral activity, indicating that large sections of the NTRs are resistant to RNA interference. Moreover, we show that naive Huh-7 cells that stably expressed certain 5′ NTR-specific shRNAs were largely resistant to a challenge with HCV replicons. These results demonstrate that the retroviral transduction of HCV-specific shRNAs provides a new possibility for antiviral intervention.
Characterization of the minimal origin required for replication of the streptococcal plasmid plP501 in Bacillus subtilis

By using deletional analysis the origin of replication, oriR, of the streptococcal plasmid plP501 in Bacillus subtilis has been mapped at a position immediately downstream of the repR gene. Determination of both the right and left border of oriR allowed the definition of a sequence of a maximum of 52 nucleotides which theoretically constitutes the minimal origin of replication. Recently, the start point of leading‐strand synthesis of the closely related plasmid pAMβ1 has been mapped at a position which is located exactly in the middle of this sequence (Bruand et al., 1991). The function of ohR did not depend on its location downstream of the repR gene. Translocation of oriR containing fragments to other regions of the plasmid proved to be possible. The smallest translocated fragment that still reconstituted autonomous replication was 72bp in size. This fragment was also active in directing the replication of an Escherichia coli plasmid in B. subtilis when the RepR protein was supplied in trans from a repR gene integrated into the host chromosome. The transformation efficiency of plasmids carrying translocated oriR fragments showed a certain dependence on the fragment length and orientation. The DNA sequence of oriR included an inverted repeat, both branches of which appeared to be essential for oriR function. The repeats of oriR shared sequence similarity with a repeat located upstream of promoter pll, which has been suggested to be involved in autoregulation of repR expression.
Transdermal estradiol therapy for advanced prostate cancer--forward to the past?

PURPOSE Current hormonal therapies for prostate cancer are associated with significant morbidities, including symptoms of andropause and osteoporosis. Oral estrogens prevented many of these problems but were abandoned due to cardiovascular toxicity attributed to hepatic effect. In contrast, parenteral estrogens prevent first pass hepatic metabolism and substantially reduce cardiovascular risk, and long-term transdermal estradiol therapy is believed to be cardioprotective. We report preliminary results of a pilot study using transdermal estradiol therapy to treat men with advanced prostate cancer. MATERIALS AND METHODS A total of 20 patients with advanced prostate cancer were enrolled in a before and after study that examined the impact of estradiol patches on hormones, disease, thrombophilia, vascular flow, osteoporosis and quality of life. RESULTS Median followup is 15 months. Estradiol levels greater than 1,000 pmol. /l. were achieved using 2 patches and higher levels were obtained by increasing the number of patches. All patients achieved castrate levels of testosterone within 3 weeks and had biochemical evidence of disease regression. One patient died of disease at 14 months and 1 cardiovascular complication occurred. Thrombophilic activation was avoided and vascular flow improved. Bone mineral density was significantly increased. Mild or moderate gynecomastia occurred in 80% of patients but no patient had hot flushes. All other functional and symptomatic quality of life domains improved. CONCLUSIONS Transdermal estradiol therapy produced an effective tumor response. Cardiovascular toxicity was substantially reduced compared with that expected of oral estrogen, and other morbidity (gynecomastia) was negligible. Transdermal estradiol therapy prevented andropause symptoms, improved quality of life scores and increased bone density. Transdermal estradiol costs a tenth of current therapy cost, with the potential for considerable economic savings over conventional hormone therapies.
Lack of Association Between Cytomegalovirus Infection and Hypertensive Disorders in Pregnancy: A Case-Control Study in Durango, Mexico

It is not clear whether infection with cytomegalovirus (CMV) is associated with hypertensive disorders in pregnant women. Through a case-control study design, 146 women suffering from hypertensive disorders in pregnancy (cases) and 146 age-matched normotensive pregnant women (controls) were examined for the presence of anti-CMV IgG and IgM antibodies with enzyme-linked immunoassays. IgM seropositive samples were further assayed by enzyme-linked fluorescent assay (ELFA). Anti-CMV IgG antibodies were found in 138 (94.5%) controls and in 136 (93.2%) cases (odds ratio [OR] = 0.78; 95% confidence interval [CI]: 0.30–2.05; P = 0.62). High (>18 IU/ml) levels of anti-CMV IgG antibodies were found in 37.7% of the 138 seropositive controls and in 34.6% of the 136 seropositive cases (OR = 0.87; 95% CI: 0.53–1.43; P = 0.59). Anti-CMV IgM antibodies were found in 1 (0.7%) of the controls but in none of the cases using ELFA (P = 1.0). Seropositivity to CMV was not associated with a previous preeclampsia and was similar among cases regardless their mean systolic and diastolic blood pressures, and mean arterial blood pressure. No serological evidence of an association between CMV infection and hypertensive disorders of pregnancy was found. Further research to elucidate the role of CMV in hypertensive disorders in pregnancy should be conducted.
Derivation of a brief measure of agitation and aggression in Alzheimer's disease

Neuropsychiatric symptoms, including agitation and aggression (A/A), are highly prevalent in Alzheimer's disease (AD) and are associated with increased disability, functional impairment, caregiver distress, and institutionalization. Previous psychometric work suggests that individual items of agitation, irritability, disinhibition, and aberrant motor behavior from the Neuropsychiatric Inventory (NPI) may be a valid measure of A/A in AD. We provide additional confirmation of this subscale, as well as preliminary validation of it as a measure of A/A (the NPI‐4‐A/A).