Miracle-dz/UniFAR-FTUs huggingface dataset:
Lung uptake of antibodies to endothelial antigens: key determinants of vascular immunotargeting.

Vascular immunotargeting is a mean for a site-selective delivery of drugs and genes to endothelium. In this study, we compared recognition of pulmonary and systemic vessels in rats by candidate carrier monoclonal antibodies (MAbs) to endothelial antigens platelet endothelial cell adhesion molecule (PECAM)-1 (CD31), intercellular adhesion molecule (ICAM)-1 (CD54), Thy-1.1 (CD90.1), angiotensin-converting enzyme (ACE; CD143), and OX-43. Tissue immunostaining showed that endothelial cells were Thy-1.1 positive in capillaries but negative in large vessels. In the lung, anti-ACE MAb provided a positive staining in 100% capillaries vs. 5-20% capillaries in other organs. Other MAbs did not discriminate between pulmonary and systemic vessels. We determined tissue uptake after infusion of 1 microg of (125)I-labeled MAbs in isolated perfused lungs (IPL) or intravenously in intact rats. Uptake in IPL attained 46% of the injected dose (ID) of anti-Thy-1.1 and 20-25% ID of anti-ACE, anti-ICAM-1, and anti-OX-43 (vs. 0.5% ID of control IgG). However, after systemic injection at this dose, only anti-ACE MAb 9B9 displayed selective pulmonary uptake (16 vs. 1% ID/g in other organs). Anti-OX-43 displayed low pulmonary (0.5% ID/g) but significant splenic and cardiac uptake (7 and 2% ID/g). Anti-Thy-1.1 and anti-ICAM-1 displayed moderate pulmonary (4 and 6% ID/g, respectively) and high splenic and hepatic uptake (e.g., 18% ID/g of anti-Thy-1.1 in spleen). The lung-to-blood ratio was 5, 10, and 15 for anti-Thy-1.1, anti-ACE, and anti-ICAM-1, respectively. PECAM antibodies displayed low pulmonary uptake in perfusion (2% ID) and in vivo (3-4% ID/g). However, conjugation with streptavidin (SA) markedly augmented pulmonary uptake of anti-PECAM in perfusion (10-54% ID, depending on an antibody clone) and in vivo (up to 15% ID/g). Therefore, ACE-, Thy-1.1-, ICAM-1-, and SA-conjugated PECAM MAbs are candidate carriers for pulmonary targeting. ACE MAb offers a high selectivity of pulmonary targeting in vivo, likely because of a high content of ACE-positive capillaries in the lungs.
Minute Foci of Gleason Score 8-10 on Prostatic Needle Biopsy: A Morphologic Analysis

Prostatic needle biopsies showing high-grade cancer typically contain abundant tumor. However, the histologic features of a minute focus of high-grade cancer on biopsy have not been well studied. A total of 100 cases with a single minute focus (≤1 mm) of Gleason score (GS) 8-10 adenocarcinoma were identified from a large consultative service, systematically studied, and compared with the submitting institutions' provisional diagnoses. The mean size of the minute foci was 0.52 mm. A total of 29 cases were GS 8 with cribriform glands (n = 15), poorly formed glands (n = 6), fused glands (n = 3), or combinations of the three (n = 5). A total of 38 cases were GS 9, with: single cells and poorly formed glands (n = 20); extremely poorly formed glands/borderline pattern 4/5 (n = 4); combinations of single cells, sheets, or nests of cells mixed with glands that were either poorly formed, cribriform, or fused (n = 14). A total of 33 cases were GS 10, with single cells (n = 23), single cells with nests (n = 9), or single cells with sheets of cells (n = 1). A total of 69 foci were located adjacent to benign glands, while 31 were on the edge or at the end of the core. Perineural invasion was observed in only 1 case. A total of 72 cases showed moderate to abundant amphophilic cytoplasm. Frequent prominent nucleoli (n = 11), mitoses (n = 8), and apoptotic bodies (n = 11) were infrequently observed. Of 59 cases with known provisional diagnoses, 46 were diagnosed as atypical (n = 37) or as cancer with GS < 8 (n = 9). Pathologists must be attuned to the complex and varied architectural patterns seen in low-volume, high-grade prostate cancer as its diagnosis has both important prognostic and therapeutic implications.
At Homeostasis Filarial Infections Have Expanded Adaptive T Regulatory but Not Classical Th2 Cells

Despite the well-documented immune suppression associated with human helminth infections, studies characterizing the immune response at the single-cell level are scanty. We used multiparameter flow cytometry to characterize the type of effector (Th1, Th2, and Th17) and regulatory (natural T regulatory cells [nTregs] and adaptive Treg cells [aTreg/type 1 regulatory cells (Tr1s)]) CD4+ and CD8+ T cells in filaria-infected (Fil+) and -uninfected (Fil−) individuals at homeostasis (in the absence of stimulation). Frequencies of CD4+ lymphocytes spontaneously producing IL-4, IL-10, and IL-17A were significantly higher in Fil+, as were those of IL-10+/IL-4+ double-producing CD4+ cells. Interestingly, frequencies of Th17 and aTreg/Tr1s but not classical Th1 or Th2 cells were significantly increased in Fil+ compared to Fil− individuals. Although the frequency of nTreg was increased in Fil+, IL-10 was overwhelmingly produced by CD4+CD25− cells. Moreover, the concentration of IL-10 produced spontaneously in vitro strongly correlated with the integrated geometric mean fluorescence intensity of IL-10–producing aTreg/Tr1s in Fil+. Together, these data show that at steady state, IL-10–producing aTreg/Tr1 as well as nTreg and effector Th17 CD4+ cells are expanded in vivo in human filarial infections. Moreover, we have established baseline ex vivo frequencies of effector and Tregs at homeostasis at a population level.
Restraining the Huddled Masses: Migration Policy and Autocratic Survival

What determines citizens’ freedom to exit autocracies? How does this influence global patterns of migration and democratization? Although control over citizen movement has long been central to autocratic power, modern autocracies vary considerably in how much they restrict emigration. This article shows that autocrats strategically choose emigration policy by balancing several motives. Increasing emigration can stabilize regimes by selecting a more loyal population and attracting greater investment, trade and remittances, but exposing their citizens to democracy abroad is potentially dangerous. Using a half-century of bilateral migration data, the study calculates the level and destinations of expected emigration given exogenous geographic and socioeconomic characteristics. It finds that when citizens disproportionately emigrate to democracies, countries are more likely to democratize – and that autocrats restrict emigration freedom in response. In contrast, a larger expected flow of economic emigration predicts autocratic survival and freer emigration policy. These results have important implications for autocratic politics, democratic diffusion and the political sources of migration.
[Urinary tract infections in a cohort of kidney transplant recipients].

INTRODUCTION Urinary tract infection is the most common infectious complication following renal transplantation and its frequency is insufficiently studied in Portugal. The aim of this study was to characterize the incidence of urinary tract infections and recurrent urinary tract infections in renal transplant recipients. MATERIAL AND METHODS This was a retrospective cohort observational study, obtained from clinical files of all patients who received a renal transplant at the Hospital of Santa Cruz, from January 2004 to December 2005, with a mean follow-up period of five years or until date of graft loss, death or loss of follow-up. After a descriptive analysis of the population, we used bivariate tests to identify risk factors for urinary tract infections. RESULTS A total of 127 patients were included, with a 593 patients.year follow-up. We detected 53 patients (41.7%) presenting with at least one episode of urinary tract infection; 21 patients (16.5%) had recurrent urinary tract infection. Female gender was the only risk factor associated with the occurrence of urinary tract infections (p < 0.001, OR = 7.08, RR = 2.95) and recurrent urinary tract infections (p < 0.001, OR = 4.66, RR = 2.83). Escherichia coli (51.6%), Klebsiella pneumoniae (15.5%) and Enterobacter spp (9.9%) were the most frequently identified pathogens. Patients did not reveal an increased mortality or allograft loss. However, urinary tract infections were the most important cause of hospital admissions. DISCUSSION Female gender was the only risk factor for urinary tract infections in this population. Escherichia coli was the most frequent agent isolated. CONCLUSION Despite preventive measures, urinary tract infections remain an important cause of morbidity and hospital admissions.
Clinical Performance Characteristics of the Cervista HPV HR Test Kit in Cervical Cancer Screening in China

Objective A multicenter clinical trial was performed to evaluate and validate the performance of Cervista HPV HR test and to establish its effectiveness in identifying women at risk of having cervical intraepithelial neoplasia 2 (CIN 2) or higher grade (CIN 2+) in the Chinese population. Materials and Methods Residual ThinPrep Pap Test samples from women who are negative for intraepithelial lesion or malignancy (NILM) and atypical squamous cells of undetermined significance (ASCUS) or higher grade cytology were tested for high-risk human papillomavirus (HPV). The HPV test results were compared with histology results to determine the clinical sensitivity, specificity, positive predictive value, and negative predictive value of Cervista HPV HR for CIN 2+. The analytical accuracy of Cervista HPV HR compared with consensus HPV L1 polymerase chain reaction (PCR)/sequencing was also determined. Result A total of 1,064 subjects were enrolled, including 544 with NILM cytology and 520 with ASCUS or higher grade cytology. Complete data sets including cytology, high-risk HPV test, colposcopy, and histology results for all subjects with ASCUS or higher grade were included in the analysis. The positive rate of Cervista HPV HR was 12.5% in patients with NILM and 69.04% in patients with ASCUS or higher grade. The overall percentage agreement between Cervista HPV HR and PCR with bidirectional sequencing was 86.26%, with positive percentage agreement and negative percentage agreement being 93.4% and 83.3%, respectively. In the overall population, the Cervista HPV HR positivity rate was 38.96% compared with 29.08% for PCR/sequencing. The clinical sensitivity and specificity for CIN 2+ of Cervista HPV HR were 98.50% and 68.21%, respectively. The negative and positive predictive values were 99.69% and 30.68%, respectively. Conclusions The Cervista HPV HR test, performed on ThinPrep Pap Test samples, has the clinical performance characteristics required by China for use as part of routine cervical cancer screening.
Primate premotor cortex: modulation of preparatory neuronal activity by gaze angle.

1. This study investigated whether the neuronal activity of a cortical area devoted to the control of limb movements is affected by variations in eye position within the orbit. Two rhesus monkeys were trained to perform a conditional visuomotor task with an instructed delay period while maintaining gaze on a fixation point. 2. The experimental design required each monkey to put its hand on a metal touch pad located at arm's length and fixate a small spot of light presented on a computer screen. Then a visual cue came on, at the fixation point or elsewhere, the color of which instructed the monkey to move its limb to one of two touch pads according to a conditional rule. A red cue meant a movement to the left, whereas a green one instructed a movement to the right. The cue lasted for a variable delay period (1-3 s), and the monkey had to wait for its offset, the go signal, before performing the correct response. The fixation point and the cues were presented at various screen locations in a combination that allowed examination of whether eye position and/or target position modulate the neuronal activity. Because the monkeys' heads were fixed, all changes in eye position reflected movements in a craniocentric, head-centered, coordinate space. 3. The activity of single neurons was recorded from dorsal premotor cortex (PMd). For most neurons (79%), the activity during the instructed delay period (set-related activity) reflects the direction of the upcoming limb movement but varies significantly with eye position. (ABSTRACT TRUNCATED AT 250 WORDS)
Identification of Four ATP-Binding Cassette Transporter Genes in Cnaphalocrocis medinalis and Their Expression in Response to Insecticide Treatment

Abstract The ATP-binding cassette (ABC) transporters belong to a superfamily of genes involved in the transport of specific molecules across lipid membranes, as well as insecticide resistance, present in all living organisms. In this study, we combined the Cnaphalocrocis medinals transcriptome database with a bioinformatics approach to identify four C. medinals ABCs (CmABCs), including CmABCG1, CmABCG4, CmABCC2 and CmABCC3. Tissue expression analysis showed that these genes had a tissue-specific expression pattern. CmABCG1 had significantly higher expression in the haemolymph and head compared to the other tissues. The expression of CmABCG4, CmABCC2 and CmABCC3 was highest in the midgut, followed by expression in the fat body. The developmental stage expression analysis showed that CmABCG1, CmABCG4, CmABCC2 and CmABCC3 were mainly expressed in adults. The transcription of CmABCG1, CmABCG4 and CmABCC2 was significantly induced by chlorpyrifos. Taken together, the results of our study provided useful information for understanding of the detoxification system of C. medinalis.
Optimization of the process of aromatic and medicinal plant maceration in grape marc distillates to obtain herbal liqueurs and spirits.

BACKGROUND Herbal liqueurs are alcoholic beverages produced by the maceration or distillation of aromatic and medicinal plants in alcohol, and are also highly valued for their medicinal properties. The process conditions, as well as the number and quantity of the plants employed, will have a great influence on the quality of the liqueur obtained. The aim of this research was to optimize these important variables. RESULTS A Box-Benhken experimental design was used to evaluate the independent variables: alcohol content, amount of plant and time during the experimental maceration of plants in grape marc distillate. Four plants were assessed, with the main compound of each plant representing the dependent variable evaluated with respect to following the evolution of the maceration process. Bisabolol oxide A in Matricaria recutita L. , linalool in Coriander sativum L. and eucalyptol in Eucalyptus globulus Labill. were quantified using a gas chromatography-flame ionization detector. Glycyrrhizic acid in Glycyrrhiza glabra L was determined using a high-performance liquid chromatography-diode array detector. Other dependent variables were also evaluated: total phenolic content, color parameters and consumer preference (i.e. appearance). CONCLUSION The experimental designs allowed the selection of the optimal maceration conditions for each parameter, including the preference score of consumers: 70% (v/v) of ethanol, 40 g L-1 plant concentration and a maceration process of 3 weeks. © 2016 Society of Chemical Industry.
Unveiling cabdrivers’ dining behavior patterns for site selection of ‘taxi canteen’ using taxi trajectory data

ABSTRACT In recent years, some big cities in China have established a number of ‘taxi canteens,’ which are special cafeterias intended only for cabdrivers to dine and rest. To dine and rest at the appropriate time is one of the most concerned problems for cabdrivers, since long dining delay may affect their health and driving safety, and arbitrary parking for dining will be fined and may even cause dangerous traffic accidents. The establishment of ‘taxi canteens’ is expected to mitigate these problems. But little has been done to examine and optimize the site selection of taxi canteens. This paper presents a data-driven approach to allocate ‘taxi canteens’ throughout a city with the main objective of minimizing the total distance between all dining demand locations identified from taxi GPS trajectories and the corresponding closest ‘taxi canteen’ locations. We propose a dining event detection method that considers four features using support vector machine and further identifies the spatiotemporal patterns of cabdrivers’ dining. A constrained optimization model is proposed to select locations for ‘taxi canteens. ’ A case study is conducted in Wuhan, China, to evaluate how the identification of cabdrivers’ dining behavior patterns can support the site selection of ‘taxi canteens. ’ The results indicate that the proposed method has superior performance.
High fat diet accelerates cartilage repair in DBA/1 mice

Obesity is a well‐known risk factor for osteoarthritis, but it is unknown what it does on cartilage repair. Here we investigated whether a high fat diet (HFD) influences cartilage repair in a mouse model of cartilage repair. We fed DBA/1 mice control or HFD (60% energy from fat). After 2 weeks, a full thickness cartilage defect was made in the trochlear groove. Mice were sacrificed, 1, 8, and 24 weeks after operation. Cartilage repair was evaluated on histology. Serum glucose, insulin and amyloid A were measured 24 h before operation and at endpoints. Immunohistochemical staining was performed on synovium and adipose tissue to evaluate macrophage infiltration and phenotype. One week after operation, mice on HFD had defect filling with fibroblast‐like cells and more cartilage repair as indicated by a lower Pineda score. After 8 weeks, mice on a HFD still had a lower Pineda score. After 24 weeks, no mice had complete cartilage repair and we did not detect a significant difference in cartilage repair between diets. Bodyweight was increased by HFD, whereas serum glucose, amyloid A and insulin were not influenced. Macrophage infiltration and phenotype in adipose tissue and synovium were not influenced by HFD. In contrast to common wisdom, HFD accelerated intrinsic cartilage repair in DBA/1 mice on the short term. Resistance to HFD induced inflammatory and metabolic changes could be associated with accelerated cartilage repair. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:1258–1264, 2017.
Expression and regulation of leptin receptor proteins in afferent and efferent neurons of the vagus nerve

Leptin, the product of the ob gene, plays a key role in the regulation of food intake via a cross‐talk between hypothalamic leptin receptors and neuropeptides that affect feeding behaviour. Recent studies have shown a synergistic interaction between leptin and cholecystokinin (CCK) leading to suppression of food intake, which involves CCK‐1 receptors and capsaicin‐sensitive vagal fibres. In this study, we have investigated the presence of leptin receptors in afferent and efferent neurons of the vagus nerve. By using reverse transcription‐polymerase chain reaction, mRNAs encoding long (Ob‐Rb) and short (Ob‐Ra) leptin receptor isoforms were detected in the rat nodose ganglion, which contains the cell bodies of the vagal afferent neurons. Western blot analysis confirmed the presence of leptin receptor‐immunoreactive proteins in extracts from the vagal trunk. Immunohistochemistry showed the presence of leptin receptors and the leptin‐induced transcription factor STAT3 in the cytoplasm of nodose ganglion cells. In cervical vagal segments, levels of leptin receptor protein displayed physiological regulation, with decreased amounts after feeding and increased levels after food restriction. In addition, leptin receptor and STAT3 immunoreactivities were detected in neurons of the nucleus of tractus solitarius (NTS) and the dorsal motor nucleus of the vagus nerve (DMNX) by immunofluorescence histochemistry. Furthermore, direct double‐labelling demonstrated colocalization of Ob‐Rb and STAT3 immunoreactivities in cholinergic vagal efferent cell bodies of the DMNX. It is speculated that vagal leptin receptors, apart from being activated by adipocyte‐derived leptin, may also be influenced by leptin produced by the stomach. This may explain the synergistic action of leptin and CCK on neuronal activity in the NTS and on food intake.
Residential traffic noise exposure and leisure-time sports – a population-based study

Traffic levels are significant environmental predictors for physical inactivity. We investigated associations between residential traffic noise and leisure-time sports. In a Danish cohort, we performed cross-sectional analyses using baseline questionnaire data (1993-97), and longitudinal analyses of change between baseline and follow-up (2000-02) in relation to participation status (yes/no), and MET hrs/week. Traffic noise was modelled based on address history from 1987-2002, available from national registries. Analyses were performed using logistic and linear regression. Traffic noise 5 years before baseline was associated with higher probability of non-participation in leisure-time sports; significantly for road traffic noise: OR 1.10 (1.07-1.13) and borderline for railway noise: OR 1.03 (0.99-1.07), per 10 dB. In longitudinal analyses, a 10 dB higher road traffic noise was associated with a higher probability of ceasing and a lower probability of initiating sports. Railway noise was negatively associated with baseline MET hrs/week, whereas no association was found in longitudinal analyses, or for road traffic noise. In conclusion, long-term exposure to residential road traffic noise, and to some degree railway noise, is negatively associated with physical activity.
Redundancy in Tumor Necrosis Factor (TNF) and Lymphotoxin (LT) Signaling In Vivo: Mice with Inactivation of the Entire TNF/LT Locus versus Single-Knockout Mice

ABSTRACT Homologous genes and gene products often have redundant physiological functions. Members of the tumor necrosis factor (TNF) family of cytokines can signal activation, proliferation, differentiation, costimulation, inhibition, or cell death, depending on the type and status of the target cell. TNF, lymphotoxin α (LTα), and LTβ form a subfamily of a larger family of TNF-related ligands with their genes being linked within a compact 12-kb cluster inside the major histocompatibility complex locus. Singly TNF-, LTα-, and LTβ-deficient mice share several phenotypic features, suggesting that TNF/LT signaling pathways may regulate overlapping sets of target genes. In order to directly address the issue of redundancy of TNF/LT signaling, we used the Cre-loxP recombination system to create mice with a deletion of the entire TNF/LT locus. Mice with a triple LTβ/TNF/LTα deficiency essentially manifest a combination of LT and TNF single-knockout phenotypes, except for microarchitecture of the spleen, where the disorder of lymphoid cell positioning and functional T- and B-cell compartmentalization is severer than that found in TNF or LT single-knockout mice. Thus, our data support the notion that TNF and LT have largely nonredundant functions in vivo.