Miracle-dz/UniFAR-FTUs huggingface dataset:
Clinical estimation of corneal endothelial pump function.

PURPOSE To develop a technique to estimate the corneal endothelial pump rate in human subjects. METHODS Corneal hydration control is thought to be maintained by a pump-leak mechanism whereby the leak of solutes and fluid across the endothelial barrier into the stroma is, in the steady state, exactly balanced by the pumping of solutes and passive fluid transfer across the endothelium to the aqueous humor. Overall corneal hydration control can be measured from the rate at which the swollen cornea thins (deswells), and a measure of the leak can be obtained simultaneously from the endothelial permeability to fluorescein. From the pump-leak hypothesis, the deswelling rate is directly proportional to the pump rate and inversely proportional to the leak rate. The relative endothelial pump rate can be estimated as the product of the normalized deswelling rate and the normalized endothelial permeability. This procedure was used to obtain the relative endothelial pump rate in 41 patients with diabetes mellitus, 12 patients with long-term corneal transplants, 20 long-term wearers of contact lenses, and 19 normal volunteer subjects after the short-term administration of topical dorzolamide. RESULTS The relative endothelial pump rate did not differ significantly from that of control subjects in diabetics, in contact lens wearers, and after dorzolamide administration, but was markedly decreased in the patients with corneal transplants, despite a reduction in permeability (reduced leak). CONCLUSIONS This method allows the estimation of both the barrier and pump arms of corneal endothelial function and should be useful in the investigation of causes and mechanisms of functional endothelial insufficiency.
Nucleoside analogs: ready to enter the era of precision medicine?

ABSTRACT Introduction: The term ‘precision medicine’ has garnered significant attention in the oncological setting in relation to attempts to optimize anticancer treatment. Precision medicine is mostly associated with oral targeted therapies and biotherapies, however, to date classic cytotoxics still remain the backbone of most regimens for treating solid tumors or in hematology, both in children and in adults. Among the existing cytotoxic therapies, nucleosides are widely used for treating a variety of cancerous diseases, alone or as part of combination therapies. Areas covered: Several markers at the tumor or the germinal levels have been identified as being associated with clinical outcome (e.g. CDA, DPD, EONFS1, hENT1, TYMS, MTHFR), however little effort has been made to implement bioguided therapy with nucleoside analogs. Still, growing clinical evidence has demonstrated how the efficacy-toxicity balance of these drugs could be improved by developing bioguided strategies at the bedside. This review covers the current knowledge regarding putative markers to be used with nucleoside analogs, what is known on their pharmacokinetic/pharmacodynamic relationships, and provides clues for implementing precision medicine with those old, yet pivotal drugs. Expert opinion: Through a variety of strategies ranging from pharmacogenetics, tumor genomics and pharmacokinetically-driven adaptive dosing procedures, nucleoside analogs could enter the era of precision medicine in oncology.
Taxonomic resolution of the ribosomal RNA operon in bacteria: implications for its use with long-read sequencing

Long-read sequencing technologies enable capture of the full-length of ribosomal RNA operons in a single read. Bacterial cells usually have multiple copies of this ribosomal operon; sequence variation within a species of bacterium can exceed variation between species. For uncultured organisms this may affect the overall taxonomic resolution, to genus level, of the full-length ribosomal operon.
Systemic adoptive T-cell immunotherapy in recurrent and metastatic carcinoma of the head and neck: a phase 1 study.

OBJECTIVE To evaluate the feasibility and toxic effects of systemic adoptive T-cell immunotherapy in patients with unresectable squamous cell carcinoma of the head and neck (SCCHN). DESIGN Nonrandomized phase 1 clinical trial. SETTING Academic tertiary care hospital. PATIENTS Between April 1, 1996, and September 30, 1998, 17 patients with confirmed recurrent and metastatic SCC of the upper aerodigestive tract were enrolled. Two patients did not receive T cells because of poor vaccine response. Fifteen patients were successfully treated with T-cell immunotherapy. INTERVENTION Patients were vaccinated on the thigh with irradiated autologous tumor cells admixed with granulocyte-macrophage colony-stimulating factor (GM-CSF) followed by 3 additional daily injections of GM-CSF at the vaccination site. Eight to 10 days later, tumor cell vaccine-draining inguinal lymph nodes were resected, and lymph node lymphocytes were activated with staphylococcal enterotoxin A and expanded in interleukin 2 in vitro. Resulting cultured cells were infused into patients peripherally on an outpatient basis. RESULTS Toxic effects of infusion were limited to grade 2 reactions in 3 of 16 treatments. One patient required overnight hospitalization for fever and emesis. Median cell expansion was 37 times (range, 4-416 times), and median cell dose was 7.5 x 10(9) (range, 1.3 x 10(8) to 4.2 x 10(10)). Infused cells were predominantly CD3+ (>97%), being a mixture of CD4+ and CD8+ cells. Three patients demonstrated stabilization of previously progressive disease. Two patients experienced favorable clinical courses after adoptive T-cell transfer, including 1 patient with no evidence of disease 4 years after surgical resection of a vertebral body metastasis. CONCLUSIONS Adoptive immunotherapy is a technically feasible and safe treatment with low toxicity and may demonstrate therapeutic activity in patients with unresectable SCCHN.
Donor Small-Droplet Macrovesicular Steatosis Affects Liver Transplant Outcome in HCV-Negative Recipients

Background No data are available on liver transplantation (LT) outcome and donor liver steatosis, classified as large droplet macrovesicular (Ld-MaS), small-droplet macrovesicular (Sd-MaS), and true microvesicular (MiS), taking into account the recipient Hepatitis C virus (HCV) status. Aim We investigate the impact of allograft steatosis reclassified according to the Brunt classification on early graft function and survival after LT. Methods We retrospectively reviewed 204 consecutive preischemia biopsies of grafts transplanted in our center during the period 2001-2011 according to recipient HCV status. Results The median follow-up after LT was 7.5 years (range: 0.0-16.7). In negative recipients (n=122), graft loss was independently associated with graft Sd-MaS, in multivariable Cox regression models comprehending only pre-/intraoperative variables (HR=1.03, 95%CI=1.01-1.05; P=0.003) and when including indexes of early postoperative graft function (HR=1.04, 95%CI=1.02-1.06; P=0.001). Graft Sd-MaS>15% showed a risk for graft loss > 2.5-folds in both the models. Graft Sd-MaS>15% was associated with reduced graft ATP content and, only in HCV- recipients, with higher early post-LT serum AST peaks. Conclusions In HCV-negative recipients, allografts with >15% Sd-MaS have significantly reduced graft survival and show low ATP and higher AST peaks in the immediate posttransplant period. Donors with >15% Sd-MaS have significantly higher BMI, longer ICU stays, and lower PaO2.
Within‐breath modulation of left ventricular function during normal breathing and positive‐pressure ventilation in man.

1. To investigate how intrathoracic pressure affects left ventricular function during normal breathing and positive‐pressure ventilation, beat‐by‐beat measurements of left ventricular stroke volume (LVSV; pulsed Doppler ultrasound), heart rate and blood pressure were made in five normal subjects breathing actively and then undergoing passive positive‐pressure ventilation. 2. To assess the within‐breath effects of positive‐pressure ventilation on left ventricular function in the clinical setting, further measurements were made in six patients sedated, paralysed and ventilated because of brain injuries, who had no disease of the heart or lungs. 3. In the normal subjects, there were minimal phasic variation in LVSV during positive‐pressure ventilation with the subject passive. Heart rate and blood pressure also stayed relatively constant throughout the ventilator cycle. During active breathing at the same depth and rate, there were large phasic respiratory variations in LVSV, with the lowest values occurring during inspiration. 4. In the paralysed and unconscious patients, an increase in LVSV was associated with the increase in airway pressure which occurred during lung inflation; however, the phase lag between the rise in airway pressure and the rise in LVSV varied widely between patients. These changes occurred whether or not sinus arrhythmia was present. 5. Addition of 4.6 +/‐ 1 cmH2O of positive end‐expiratory pressure (PEEP) did not increase the within‐breath LVSV variations, but resulted in a mean depression of LVSV of 5.4% (paired t test, P = 0.035). 6. The smaller variations in LVSV during positive‐pressure ventilation compared to normal breathing in the conscious subjects may reflect (a) the smaller magnitude of positive, compared to negative, pleural pressure excursions which accompany a given tidal volume, and (b) an asymmetry between the effects of positive and negative pleural pressure on the heart. 7. The prominent effects of positive‐pressure ventilation on LVSV in unconscious patients, compared to the minimal effects seen in ventilated normal subjects, may result from reduced lung compliance and a degree of pulmonary vascular congestion in the patients which was undetectable clinically or radiologically.
The use of paracetamol (acetaminophen) among a community sample of people with chronic non‐cancer pain prescribed opioids

The regular use of simple analgesics in addition to opioids such as paracetamol (or acetaminophen) is recommended for persistent pain to enhance analgesia. Few studies have examined the frequency and doses of paracetamol among people with chronic non‐cancer pain including use above the recommended maximum daily dose.
Unsupervised learning technique for surface electromyogram denoising from power line interference and baseline wander

We present a novel approach to single-channel power line interference (PLI) and baseline wander (BW) removal from surface electromyograms (EMG). It is based on non-negative matrix factorization (NMF) using a priori knowledge about the interferences. It performs a linear decomposition of the input signal spectrogram into non-negative components, which represent the PLI, BW and EMG spectrogram estimates. They all exhibit very different time-frequency patterns: PLI and BW are both sparse whereas EMG is noise-like. Initialization of the classical NMF algorithm with accurately designed PLI, BW and EMG structures and a carefully adjusted matrix decomposition rank increases the separation performance. The comparative study suggests that the proposed method outperforms two state-of-the-art reference methods.
Prognostic significance of admission levels of troponin I in patients with acute ischaemic stroke

Objectives: Successful prediction of cardiac complications early in the course of acute ischaemic stroke could have an impact on the clinical management. Markers of myocardial injury on admission deserve investigation as potential predictors of poor outcome from stroke. Methods: We prospectively investigated 330 consecutive patients with acute ischaemic stroke admitted to our emergency department based stroke unit. We analysed the association of baseline levels of cardiac troponin I (cTnI) with (a) all-cause mortality over a six month follow up, and (b) inhospital death or major non-fatal cardiac event (angina, myocardial infarction, or heart failure). Results: cTnI levels on admission were normal (lower than 0.10 ng/ml) in 277 patients (83.9%), low positive (0.10–0.39 ng/ml) in 35 (10.6%), and high positive (0.40 ng/ml or higher) in 18 (5.5%). Six month survival decreased significantly across the three groups (p<0.0001, log rank test for trend). On multivariate analysis, cTnI level was an independent predictor of mortality (low positive cTnI, hazard ratio (HR) 2.14; 95% CI 1.13 to 4.05; p = 0.01; and high positive cTnI, HR 2.47; 95% CI 1.22 to 5.02; p = 0.01), together with age and stroke severity. cTnI also predicted a higher risk of the combined endpoint “inhospital death or non-fatal cardiac event”. Neither the adjustment for other potential confounders nor the adjustment for ECG changes and levels of CK-MB and myoglobin on admission altered these results. Conclusions: cTnI positivity on admission is an independent prognostic predictor in acute ischaemic stroke. Whether further evaluation and treatment of cTnI positive patients can reduce cardiac morbidity and mortality should be the focus of future research.
Multiple widely spaced elements determine the efficiency with which a distal cistron is expressed from the polycistronic pregenomic RNA of figwort mosaic caulimovirus

The polycistronic expression mechanism of the plant pararetrovirus figwort mosaic caulimovirus (FMV) depends upon cis-acting elements present in its pregenomic RNA and a trans-acting protein (P6) which is expressed from a monocistronic subgenomic RNA. Using transient expression of FMV-derived polycistronic reporter constructs in Nicotiana edwardsonii cell suspension protoplasts, we further analyzed the cis-acting elements involved in polycistronic expression. A cis-acting element located within the first 74 nucleotides of the 7,954-nucleotide pregenomic RNA appears to be essential for P6 to transactivate expression of an internal cistron. Expression of this internal cistron, in the presence of P6, is greatly enhanced by the combined presence of two cis-acting elements located at the 3' end of the polycistronic RNA. Surprisingly, deletion of the most upstream of these two 3' cis-acting elements exposed a negative-acting element located internally on the polycistronic RNA, at the 3' end of open reading frame I. The action of both this negative-acting internal element and the positive-acting 3' elements is more pronounced when the large 5' untranslated leader region is present. This indicates that the 5' untranslated leader region is central to regulation of the FMV gene expression mechanism. Although a limited set of elements suffices to direct polycistronic expression in this eukaryotic system, a complex interplay between elements is involved in the spatial regulation of the genes present on the pregenomic RNA of FMV.
Proteomic and Transcriptomic Elucidation of the Mutant Ralstonia eutropha G+1 with Regard to Glucose Utilization

ABSTRACT By taking advantage of the available genome sequence of Ralstonia eutropha H16, glucose uptake in the UV-generated glucose-utilizing mutant R. eutropha G+1 was investigated by transcriptomic and proteomic analyses. Data revealed clear evidence that glucose is transported by a usually N-acetylglucosamine-specific phosphotransferase system (PTS)-type transport system, which in this mutant is probably overexpressed due to a derepression of the encoding nag operon by an identified insertion mutation in gene H16_A0310 (nagR). Furthermore, a missense mutation in nagE (membrane component EIICB), which yields a substitution of an alanine by threonine in NagE and may additionally increase glucose uptake, was identified. Phosphorylation of glucose is subsequently mediated by NagF (cytosolic PTS component EIIA-HPr-EI) or glucokinase (GlK), respectively. The inability of the defined deletion mutant R. eutropha G+1 ΔnagFEC to utilize glucose strongly confirms this finding. In addition, secondary effects of glucose, which is now intracellularly available as a carbon source, on the metabolism of the mutant cells in the stationary growth phase occurred: intracellular glucose degradation is stimulated by the stronger expression of enzymes involved in the 2-keto-3-deoxygluconate 6-phosphate (KDPG) pathway and in subsequent reactions yielding pyruvate. The intermediate phosphoenolpyruvate (PEP) in turn supports further glucose uptake by the Nag PTS. Pyruvate is then decarboxylated by the pyruvate dehydrogenase multienzyme complex to acetyl coenzyme A (acetyl-CoA), which is directed to poly(3-hydroxybutyrate). The polyester is then synthesized to a greater extent, as also indicated by the upregulation of various enzymes of poly-β-hydroxybutyrate (PHB) metabolism. The larger amounts of NADPH required for PHB synthesis are delivered by significantly increased quantities of proton-translocating NAD(P) transhydrogenases. The current study successfully combined transcriptomic and proteomic investigations to unravel the phenotype of this hitherto-undefined glucose-utilizing mutant.
PRSS3 is a prognostic marker in invasive ductal carcinoma of the breast

Objective Serine protease 3 (PRSS3) is an isoform of trypsinogen, and plays an important role in the development of many malignancies. The objective of this study was to determine PRSS3 mRNA and protein expression levels in invasive ductal carcinoma of the breast and normal surrounding tissue samples. Results Both PRSS3 mRNA and protein levels were significantly higher in invasive ductal carcinoma of the breast tissues than in normal or benign tissues (all P < 0.05). High PRSS3 protein levels were associated with patients’ age, histological grade, Her-2 expression level, ki-67 expression, and the 5.0-year survival rate. These high protein levels are independent prognostic markers in invasive ductal carcinoma of the breast. Materials and Methods We used real-time quantitative polymerase chain reactions (N = 40) and tissue microarray immunohistochemistry analysis (N = 286) to determine PRSS3 mRNA and protein expression, respectively. PRSS3 protein levels in invasive ductal carcinoma of the breast tissues were correlated with the clinical characteristics of patients with invasive ductal carcinoma of the breast and their 5.0-year survival rate. Conclusions PRSS3 acts as an oncogene in invasive ductal carcinoma of the breast development and progression. This finding implies that detection of PRSS3 expression can be a useful prognosis marker and the targeting of PRSS3 can potentially represent a new strategy for invasive ductal carcinoma of the breast treatment.
Is Risk Taking or Moral Hazard Beneficial to the Insured and the Society?

In this article, we discuss whether and when the risk taking and moral hazard is beneficial to the insured and to the society as well. We establish model by stochastic optimal control theory. We obtain the optimal levels of risk taking and moral hazard from perspectives of the insured and the society. Finally we make some discussions on insurance and moral hazard.
Multiple description coding using multiple reference frame for robust video transmission

Multiple description coding is an error-resilient coding method that encodes a video sequence into several bitstreams, called descriptions. The main problem of multiple description coding is the mismatch of reference frames in encoder and decoder, when the descriptions are lost during transmission. The mismatch is also referred to as drift and can be alleviated efficiently by transmitting side information along with each description. We introduce a new generation scheme for side information, which is based on multiple reference frames. For each encoding frame, two previously encoded frames are used as the reference frame's I motion prediction. The prediction results of two reference frames are encoded as descriptions and side information respectively. When transmission errors occur in either reference frame, the decoder can use the correctly received reference frame in decoding. Simulation results prove that the proposed method can improve video quality obviously along different macroblock loss rates.
Oil and Unbalanced Globalization

We demonstrate that oil wealth is associated with both high levels of economic and social integration and low levels of political integration – a condition we call “unbalanced globalization,” in contrast to more balanced globalization of other countries. We develop and examine three plausible explanations for it. First, oil wealth may retard democratization, which may in turn reduce political integration. Second, oil rich states are able to attract foreign investments and have access to world markets without tying their hands to institutions. Third, oil-rich states export an unusually narrow range of goods, which reduces domestic coalitions in favor of integration. Our evidence primarily points to the second and third mechanisms.
Sesquiterpene Lactones from Inula hupehensis Inhibit Nitric Oxide Production in RAW264.7 Macrophages

Abstract Phytochemical investigation of the aerial parts of Inula hupehensis Ling. led to the isolation and identification of 27 sesquiterpene lactones (1–27), including three new eudesmanolides (3–5), three new germacranolides (9–11), one new xanthanolide (16), two new carabrone derivatives (25–26), and 18 known sesquiterpene lactones. The structures were elucidated by extensive spectroscopic methods and comparison to previously reported spectroscopic data. All compounds were evaluated for their inhibitory effects against LPS-induced nitric oxide production in RAW264.7 macrophages, and compound 5 showed the strongest activity with the IC50 value of 3.2 ± 0.4 µM.
ICT Governance: A Reference Framework

This article deals with information and communication technology (ICT) governance, a topic that has been discussed in the literature over the last 20 years. In order to offer a conceptualized view of the ICT governance models adopted by companies, a theoretical framework has been developed. A review of the available literature dealing with ICT governance, as well as a critical analysis of 27 case studies, was carried out, with the aim of highlighting the variables of the proposed framework.
Analysis of gene expression EGFR and KRAS, microRNA-21 and microRNA-203 in patients with colon and rectal cancer and correlation with clinical outcome and prognostic factors.

Purpose: To evaluate the expression of EGFR, KRAS genes, microRNAs-21 and 203 in colon and rectal cancer samples, correlated with their age at diagnosis, histological subtype, value of pretreatment CEA, TNM staging and clinical outcome. Methods: Expression of genes and microRNAs by real time PCR in tumor and non-tumor samples obtained from surgical treatment of 50 patients. Results: An increased expression of microRNAs-21 and 203 in tumor samples in relation to non-tumor samples was found. There was no statistically significant difference between the expression of these genes and microRNAs when compared to age at diagnosis and histological subtype. The EGFR gene showed higher expression in relation to the value of CEA diagnosis. The expression of microRNA-203 was progressively lower in relation to the TNM staging and was higher in the patient group in clinical remission. Conclusions: The therapy of colon and rectum tumors based on microRNAs remains under investigation reserving huge potential for future applications and clinical interventions in conjunction with existing therapies. We expect, based on the exposed data, to stimulate the development of new therapeutic possibilities, making the treatment of these tumors more effective.
Assessment of cytology and mucin 2 in colorectal mucus collected from patients with inflammatory bowel disease: Results of a pilot trial

Non‐invasive diagnosis of colorectal disease remains problematic, fecal biomarkers presenting the only current option. Colorectal mucus is the diagnostically informative element of stool samples, but its separation from stool is difficult. We aimed to: (i) test a novel method of non‐invasive colorectal mucus sampling in a pilot clinical trial; (ii) evaluate sampling method acceptance by study participants; (iii) characterize the collected material cytologically; and (iv) assess feasibility of quantitative protein analysis in the samples.