Miracle-dz/UniFAR-FTUs huggingface dataset:
Blockade of CXCR2 signalling: A potential therapeutic target for preventing neutrophil-mediated inflammatory diseases

Polymorphonuclear neutrophils (PMN) play a key role in host innate immune responses by migrating to the sites of inflammation. Furthermore, PMN recruitment also plays a significant role in the pathophysiology of a plethora of inflammatory disorders such as chronic obstructive pulmonary disease (COPD), gram negative sepsis, inflammatory bowel disease (IBD), lung injury, and arthritis. Of note, chemokine-dependent signalling is implicated in the amplification of immune responses by virtue of its role in PMN chemotaxis in most of the inflammatory diseases. It has been clinically established that impediment of PMN recruitment ameliorates disease severity and provides relief in majority of other immune-associated disorders. This review focuses on different novel approaches clinically proven to be effective in blocking chemokine signalling associated with PMN recruitment that includes CXCR2 antagonists, chemokine analogs, anti-CXCR2 monoclonal antibodies, and CXCR2 knock-out models. It also highlights the significance of the utility of nanoparticles in drugs used for blocking migration of PMN to the sites of inflammation.
Chemotherapy of advanced measurable colon and rectal carcinoma with oral 5‐fluorouracil, alone or in combination with cyclophosphamide or 6‐thioguanine, with intravenous 5‐fluorouracil or beta‐2′‐deoxythioguanosine or with oral 3(4‐methyl‐cyclohexyl)‐1(2‐chlorethyl)‐1‐nitrosourea. A phase II‐III stu

In a randomized multi‐institutional trial of the Eastern Cooperative Oncology Group, 316 patients with advanced measurable colorectal adenocarcinoma were treated with a weekly schedule of 5‐fluorouracil given orally and intravenously with oral 5‐fluorouracil in combination with cyclophosphamide or 6‐thioguanine, or with oral Methyl CCNU administered once every eight weeks. On failure or progression, 133 protocol patients crossed‐over to a secondary therapy, while 116 other patients previously treated with 5‐fluorouracil off protocol were randomized to treatment with Methyl CCNU or B‐2′‐deoxythio‐guanosine. Response rates among patients who had received no prior chemotherapy were 18% to oral 5‐FU, 15% to intravenous 5‐FU and to MeCCNU, 12% to 5‐FU and 6‐thioguanine and 5% to cyclophosphamide and 5‐FU, with little activity (3% response rate) in crossover or previously treated patients. Treatment with 5‐FU, particularly oral 5‐FU was associated with the least drug‐related toxicity. Hematologic toxicity was greatest with Methyl CCNU, but was no more frequent in previously treated than in untreated patients. A tendency toward cumulative bone marrow depression was noted. 5‐FU was effective only in ambulatory patients, whereas responses among non‐ambulatory patients were seen only in the group treated with Methyl‐CCNU. Cancer 42:2538–2545, 1978.
Salivary steroid assays – research or routine?

Salivary concentrations of unconjugated steroids reflect those for free steroids in serum although concentrations may differ because of salivary gland metabolism. Samples for salivary steroid analysis are stable for up to 7 days at room temperature, one month or more at 4°C and three months or more at −20°C. When assessed against strict criteria, the evidence shows that salivary cortisol in evening samples or following dexamethasone suppression provides a reliable and effective screen for Cushing's syndrome. Sequential salivary cortisol measurements are also extremely helpful for the investigation of suspected cyclical Cushing's syndrome. There is potential for the identification of adrenal insufficiency when used with Synacthen stimulation. Salivary 17-hydroxyprogesterone and androstenedione assays are valued as non-invasive tests for the home-monitoring of hydrocortisone replacement therapy in patients with congenital adrenal hyperplasia due to 21-hydroxylase deficiency. The diagnostic value of salivary oestradiol, progesterone, testosterone, dehydroepiandrosterone and aldosterone testing is compromised by rapid fluctuations in salivary concentrations of these steroids. Multiple samples are required to obtain reliable information, and at present the introduction of these assays into routine laboratory testing is not justified.
Level of Physical Activity in the Week Preceding an Ischemic Stroke

Background: Most observational studies investigating physical activity as a risk factor for stroke have concentrated on the years preceding a stroke event. In the present case control study we compared the reported level of physical activity performed during the week preceding an ischemic stroke with that of community controls. Furthermore we calculated the odds ratio for stroke based on the level of physical activity. Subjects and Methods: Patients with an ischemic stroke were recruited consecutively from hospitals covering Copenhagen City. Community controls were recruited among participants of the Copenhagen City Heart Study and matched according to age and gender. The level of physical activity was assessed using The Physical Activity Scale for the Elderly (PASE), which quantifies the amount of physical activity done in the last 7 days. Results: A total of 127 cases and 301 control subjects were included in the study. Mean (±SD) PASE scores for cases were 76.0 ± 46.2 and 119.7 ± 69.4 for controls (p < 0.001). For each 1-point increase in PASE score the odds ratio for ischemic stroke was 0.98 (0.98–0.99), equivalent to an odds ratio of 0.86 (95% CI: 0.82–0.90) for each 10-point increase. Conclusion: Stroke patients are less physically active in the week preceding an ischemic stroke when compared to age- and sex-matched controls. Increasing PASE score was inversely, log-linearly and significantly associated with odds ratio for ischemic stroke.
Chimeric receptors of the Arabidopsis thaliana pattern recognition receptors EFR and FLS2

FLS2 and EFR are pattern recognition receptors in Arabidopsis thaliana perceiving the bacterial proteins flagellin and Elongation factor Tu (EF-Tu). Both receptors belong to the >200 membered protein family of Leucine-Rich Repeat Receptor Kinases (LRR-RKs) in Arabidopsis. FLS2 and EFR are engaged in the activation of a common intracellular signal output and they belong to the same subfamily of LRR-RKs, sharing structural features like the intracellular kinase domain and the ectodomain organized in LRRs. On the amino acid sequence level, however, they are only <50 % identical even in their kinase domains. In our recently published paper1 we demonstrated that it is possible to create chimeric receptors of EFR and FLS2 which are fully functional in ligand binding and receptor activation. Chimeric receptors consisting of the complete EFR ectodomain and the FLS2 kinase domain proved to be sensitive to elf18, the minimal peptide required for EF-Tu recognition, similar to the native EFR. In chimeric receptors where parts of the FLS2 ectodomain were swapped into the EFR LRR-domain, the receptor function was strongly affected even in cases with only small fragments exchanged. In this addendum we want to address problems and limits but also possibilities and chances of studying receptor functions using a chimeric approach.
PCR DIAGNOSTICS UNDERESTIMATE THE PREVALENCE OF AVIAN MALARIA (PLASMODIUM RELICTUM) IN EXPERIMENTALLY-INFECTED PASSERINES

Several polymerase chain reaction (PCR)-based methods have recently been developed for diagnosing malarial infections in both birds and reptiles, but a critical evaluation of their sensitivity in experimentally-infected hosts has not been done. This study compares the sensitivity of several PCR-based methods for diagnosing avian malaria (Plasmodium relictum) in captive Hawaiian honeycreepers using microscopy and a recently developed immunoblotting technique. Sequential blood samples were collected over periods of up to 4.4 yr after experimental infection and rechallenge to determine both the duration and detectability of chronic infections. Two new nested PCR approaches for detecting circulating parasites based on P. relictum 18S rRNA genes and the thrombospondin-related anonymous protein (TRAP) gene are described. The blood smear and the PCR tests were less sensitive than serological methods for detecting chronic malarial infections. Individually, none of the diagnostic methods was 100% accurate in detecting subpatent infections, although serological methods were significantly more sensitive (97%) than either nested PCR (61–84%) or microscopy (27%). Circulating parasites in chronically infected birds either disappear completely from circulation or to drop to intensities below detectability by nested PCR. Thus, the use of PCR as a sole means of detection of circulating parasites may significantly underestimate true prevalence.
Relationship Among Glycolytic Phenotype, Grade, and Histological Subtype in Ovarian Carcinoma

Purpose: Knowing the glycolytic phenotype of cancers is important for the appropriate use of F-18 FDG PET/CT imaging. This study was performed to determine the influence of tumor grade and histology on the glycolytic phenotype of epithelial ovarian cancer patients. Materials and Methods: Only histopathologically confirmed epithelial ovarian cancer patients, with no other concurrent malignancies, who had F-18 FDG PET/CT either before or at least 3 months after any therapeutic intervention and had confirmed measurable disease of >1 cm were included. The F-18 FDG PET/CT uptake was determined as maximum standard uptake value (SUVmax) at the pathologically confirmed site of disease or in the most active lesion. SUVmax was correlated to tumor grade and histology. Results: Of 171 ovarian cancer patients, 42 referred for F-18 FDG PET/CT scans between January 2003 and December 2010 were eligible for inclusion. Histologic diagnosis most frequently revealed the serous subtype (n = 32) and grade III (n = 28) epithelial ovarian cancer. Overall, ovarian carcinomas exhibited a strong glycolytic phenotype (average SUVmax, 7.6 g/mL). The SUVmax averaged 7.76 g/mL, 6.76 g/mL, and 7.95 g/mL for Grade I, II, and III, respectively. There was no statistically significant correlation between tumor SUVmax and the histologic tumor grade (P = 0.74). No statistically significant differences were found between the tumor SUVmax of serous and endometrioid subtypes (P = 0.53). For other histology subtypes, no statistic evaluation was possible due to the low number of cases. Conclusions: The glycolytic phenotype in epithelial ovarian cancer, expressed as SUVmax, is strong. However, tumor FDG uptake is unrelated to tumor grade and histologic subtype implying that F-18 FDG PET/CT cannot be used to predict tumor aggressiveness or histology.
Malingering on the Social Security Disability Consultative Exam: Predictors and Base Rates

The Disability Determinations Service (DDS) obtains evidence about an applicant from sources that may include the Psychological Consultative Examination (PCE), which usually includes a mental status examination and Wechsler Scale findings. Although evidence for good effort is necessary to validate the findings, psychologists have been officially discouraged from determining effort by the use of formal tests. In Chafetz, Abrahams, and Kohlmaier (2007), indicators of effort within the PCE in WAIS-age (adults) and WISC-age (children) claimants were determined, and a PCE Malingering Rating Scale was developed. In the present study, this new scale was used along with established symptom validity tests (SVTs) to determine base rates and additional predictors of malingering within the PCE. Claimants were apportioned into separate effort groups in a “dose–response” manner: Definite Malingerers, Chance-Level, Fail Both (SVT and Rating Scale), Fail One, Fail Indicators, and Not Fail. Data from separate studies using the Test of Memory Malingering (TOMM), and the Medical Symptom Validity Test (MSVT) were used to assign claimants into separate effort groups. An evidence-based assessment approach utilized these base-rates to calculate post-test odds. Other predictors of effort within the PCE include the presence of conduct disorder symptoms, and the number of other family members on Disability.
A Concise Review on Multi-Omics Data Integration for Terroir Analysis in Vitis vinifera

Vitis vinifera (grapevine) is one of the most important fruit crops, both for fresh consumption and wine and spirit production. The term terroir is frequently used in viticulture and the wine industry to relate wine sensory attributes to its geographic origin. Although, it can be cultivated in a wide range of environments, differences in growing conditions have a significant impact on fruit traits that ultimately affect wine quality. Understanding how fruit quality and yield are controlled at a molecular level in grapevine in response to environmental cues has been a major driver of research. Advances in the area of genomics, epigenomics, transcriptomics, proteomics and metabolomics, have significantly increased our knowledge on the abiotic regulation of yield and quality in many crop species, including V. vinifera. The integrated analysis of multiple ‘omics’ can give us the opportunity to better understand how plants modulate their response to different environments. However, ‘omics’ technologies provide a large amount of biological data and its interpretation is not always straightforward, especially when different ‘omic’ results are combined. Here we examine the current strategies used to integrate multi-omics, and how these have been used in V. vinifera. In addition, we also discuss the importance of including epigenomics data when integrating omics data as epigenetic mechanisms could play a major role as an intermediary between the environment and the genome.
Intracellular localization of the mRNAs of argininosuccinate synthetase and argininosuccinate lyase around liver mitochondria, visualized by high‐resolution in situ reverse transcription‐polymerase chain reaction

Argininosuccinate synthetase and argininosuccinate lyase, two cytoplasmic enzymes of the urea cycle, are released into the soluble phase in the absence of detergent when cells are disrupted. Yet previous biochemical studies, as well as immunocytochemistry at the electron microscope level, have shown that these enzymes are localized around mitochondria in situ. Such intracellular localization of soluble enzymes requires mechanisms to deliver the proteins to the appropriate sites, where they may then be anchored by specific protein‐protein interactions. A method was developed to examine the intracellular distribution of the mRNA of argininosuccinate synthetase and argininosuccinate lyase in intact rat liver at the ultrastructural level by in situ reverse transcription and the polymerase chain reaction, using primers targeting regions of the coding sequences of the rat enzymes, digoxigenin‐dUTP as the label, and anti‐digoxigenin/10 nm gold plus silver enhancement as the detection method. The tissue was fixed in 4% paraformaldehyde/0.1% glutaraldehyde and embedded in Lowicryl. Examination of the numbers and the location of the silver grains, coupled with morphometric analysis of the electron micrographs, permitted the calculation of the silver “enrichment ratio” for each type of cell structure. These ratios showed that the mRNAs for argininosuccinate synthetase and argininosuccinate lyase were located next to the cytoplasmic side of the mitochondrial membrane and in the nearby endoplasmic reticulum. Most of the silver grains that were observed in the endoplasmic reticulum were within 200 nm of the mitochondria; it was not possible, however, to determine if those grains were actually associated with the reticular membranes. These studies demonstrate that the mRNAs of these two soluble cytoplasmic proteins are localized to the same limited regions where the proteins are situated. Translation of the proteins, therefore, must occur at these specific sites. The targeting of argininosuccinate synthetase and argininosuccinate lyase mRNAs to the immediate vicinity of the mitochondria may be the first step of the mechanisms by which the spatial organization of these soluble proteins in situ is accomplished. The targeting of mRNAs for soluble cytoplasmic proteins of organized metabolic pathways has not been demonstrated previously. These studies also show that in situ reverse transcription and the polymerase chain reaction at the ultrastructural level, which has not been previously reported, can be used to detect specific mRNAs; it should be extremely valuable for the intracellular detection of low‐abundance mRNAS. © 1996 Wiley‐Liss, Inc.
Docetaxel in non-small cell lung cancer: a review

Docetaxel (Taxotere™, Aventis Pharma), a semisynthetic taxane targeting the β-subunit of tubulin, has broad spectrum anticancer activity including non-small cell lung cancer (NSCLC). It is synergistic with platinum and radiation in preclinical models and has been tested clinically in every stage of NSCLC. Docetaxel–platinum combinations have an efficacy comparable to other newer-agent platinum doublets as first-line therapy in advanced NSCLC, and has been approved for use in this setting. Docetaxel was initially approved for NSCLC in the second-line setting following two Phase III trials demonstrating improved survival and quality of life. Ongoing clinical trials are investigating how best to combine docetaxel with thoracic radiotherapy in locally advanced disease. Preliminary studies evaluating docetaxel in the pre-operative setting have also been completed. Ongoing studies are focused on confirming the results observed with consolidation docetaxel in locally advanced NSCLC (SWOG 9504) and docetaxel in combination with molecularly targeted agents. This paper will review the pharmacology, preclinical, clinical and pharmacoeconomic data supporting the use of docetaxel in the treatment NSCLC.
Health status impairment and costs associated with COPD exacerbation managed in hospital

Exacerbations of chronic obstructive pulmonary disease (COPD) have serious health consequences for patients and are strongly associated with unscheduled healthcare resource use. This study used a preference‐based quality of life measure questionnaire (EQ‐5D) to evaluate the impact of exacerbation on health status and utility during a patient's admission to hospital and short‐term follow‐up. Costs of admission were calculated. In total, 149 patients consented to take part in the study representing 222 admissions to hospital. At admission patients reported high levels of problems for all dimensions of the EQ‐5D. Mean utility (−0.077) and Visual Analogue Scale (25.9) values indicated great impairment, with 61% of patients having a negative utility value representing a health state equivalent to ‘worse than death’ at admission. Many problems were still reported at discharge. By 3 months follow‐up patients had deteriorated, with percentages of patients reporting problems in mobility (98%) and usual activity (88%) almost back up to admission levels. Health status and utility values were similar regardless of lung function at admission and at discharge. Approximately half of the patients in each category had a negative utility value at admission representing a health state ‘worse than death’, with similar levels of improvement by discharge. The mean cost of an admission was £2130.34 (SD 1326.09) with only a mean of £110.37 (5%) because of medication. No differences were noted by lung function category. In conclusion, all COPD patients requiring admission for an exacerbation suffer a serious deterioration in health status which, although improves during admission, notably deteriorates by 3 months postdischarge.
Machine vision based recognition of emotions using the circumplex model of affect

In the vision community recognition and analysis of facial expressions is a long investigated area of research with potential applications such as human computer interaction (HCI). Most state of the art techniques focus on recognition of defined facial expression categories, i.e. basic emotions. However, in HCI classical basic emotions are only occurring sparsely, thus they are inadequate to guide the dialog with the user. Here we suggest a mapping to the so called circumplex model of affect, known from psychology. This enables us to determine the current affective state of the user, which can then be used to control the course of the interaction. In particular, the output of the proposed machine vision based recognition method gives insight to the observed person's arousal state and the valence along two axes of the 2-D plane of the underlying circumplex model. In this paper we present the basic principles of our new method and present first results.
Steroid‐Free Immunosuppression Since 1999: 129 Pediatric Renal Transplants with Sustained Graft and Patient Benefits

Despite early promising patient and graft outcomes with steroid‐free (SF) immunosuppression in pediatric kidney transplant recipients, data on long‐term safety and efficacy results are lacking. We present our single‐center experience with 129 consecutive pediatric kidney transplant recipients on SF immunosuppression, with a mean follow‐up of 5 years. Outcomes are compared against a matched cohort of 57 concurrent recipients treated with steroid‐based (SB) immunosuppression. In the SF group, 87% of kidney recipients with functioning grafts remain corticosteroid‐free. Actual intent‐to‐treat SF (ITT‐SF) and still‐on‐protocol SF patient survivals are 96% and 96%, respectively, actual graft survivals for both groups are 93% and 96%, respectively and actual death‐censored graft survivals for both groups are 97% and 99%, respectively. Unprecedented catch‐up growth is observed in SF recipients below 12 years of age. Continued low rates of acute rejection, posttransplant diabetes mellitus (PTDM), hypertension and hyperlipidemia are seen in SF patients, with sustained benefits for graft function. In conclusion, extended enrollment and longer experience with SF immunosuppression for renal transplantation in low‐risk children confirms protocol safety, continued benefits for growth and graft function, low acute rejection rates and reduced cardiovascular morbidity.
On Seeking the Truth (Whatever That Is) through Democracy: Estlund’s Case for the Qualified Epistemic Claim*

In Democratic Authority David Estlund advances what I call the “Qualified Epistemic Claim,” according to which democracy is the best epistemic strategy for revealing the truth from among those strategies that are generally acceptable. I examine this claim, focusing on three issues: the scope of truth claims for which it applies, the test by which we know whether democracy is best, and the mechanism by which democracy has this supposed benefit. I conclude that although Estlund has presented some suggestive considerations in favor of the Qualified Epistemic Claim, he does not present a convincing case for it.
Biopsy-verified response of severe lupus nephritis to treatment with rituximab (anti-CD20 monoclonal antibody) plus cyclophosphamide after biopsy-documented failure to respond to cyclophosphamide alone

Background: The monoclonal anti-B cell antibody rituximab (Rituxin, Mabthera) may be of benefit in antibody-driven diseases, including systemic lupus erythematosus (SLE) nephritis. Patients and treatment: Two female patients with biopsy-confirmed severe and active SLE nephritis despite treatment with cyclophosphamide (CyX) were given four rituximab infusions plus two additional CyX infusions. Results: Both patients tolerated the treatment well and SLE activity improved. On repeat kidney biopsy after the combined treatment, Patient 1 showed a profound reduction of nephritis activity, and she was maintained on low-dose prednisolone only. A repeat biopsy after 1 year confirmed the sustained reduction of lupus nephritis activity. In Patient 2, rebiopsy after combined treatment also showed a significant reduction in disease activity. Conclusion: These cases provide histopathological documentation of a significant treatment benefit from rituximab plus CyX in two patients refractory to CyX alone. This combination is being explored further as salvage therapy for such CyX-resistant patients.