Miracle-dz/UniFAR-FTUs huggingface dataset:
Advances in targeted delivery of small interfering RNA using simple bioconjugates

Introduction: Development of drugs based on RNA interference by small interfering RNA (siRNA) has been progressing slowly due to a number of challenges associated with the in vivo behavior of siRNA. A central problem is controlling siRNA delivery to specific cell types. Here, we review existing literature on one type of strategy for solving the issue of cell-specific delivery of siRNA, namely delivering the siRNA as part of simple bioconjugate constructs. Areas covered: This review presents current experience from strategies aimed at targeting siRNA to specific cell types, by associating the siRNA with a targeting moiety, in a simple bioconjugate construct. We discuss the use of different types of targeting moieties, as well as the different conjugation strategies employed for preparing these bioconjugate constructs that deliver the siRNA to target cells. We focus especially on the in-built or passive functionalities associated with each strategy, in order to identify key elements of successful siRNA delivery strategies with potential for further exploration. Expert opinion: By evaluating the current literature on this subject, we identify strategies and concepts that are suitable for future studies, to enable the development of highly efficient simple bioconjugates for targeted siRNA delivery with therapeutic application.
A genuine realist theory of advanced modalizing

The principle of modal ubiquity-that every truth is necessary or contingent-and the validity of possibility introduction, are principles that any modal theory suffers for failing to accommodate. Advanced modal claims are modal claims about entities other than spatiotemporally unified individuals (perhaps, then, spatiotemporally disunified individuals, sets, numbers, properties, propositions and events). I show that genuine modal realism, as it has thus far been explicitly developed, and in so far as it deals with advanced modal claims, cannot accommodate the principles in question. On behalf of the genuine modal realist I motivate and propose a redundancy interpretation of advanced possibility claims and extend that interpretation to the cognate cases of necessity, impossibility and contingency. I then show that the problematic principles as they apply to advanced modal claims can be derived from these interpretations. I show further how the proposed interpretation enables the genuine modal realist to deal with a number of objections that centre on the alleged inadequacy of the genuine modal realist's expressive resources. I conclude that genuine modal realism emerges the stronger for having been shown capable of dealing with advanced modal claims on the basis of no conceptual and ontological resources beyond those it requires to deal with ordinary modal claims.
Biochemical Responses of Yankasa Sheep to Experimental Fasciola gigantica Infection in Zaria, Nigeria

A study was conducted to determine the biochemical responses of Yankasa ewes to experimental Fasciola gigantica infection for a period of 10 weeks. A total of 12 Yankasa ewes were used in the experiment and were obtained from the Reproduction Unit of the National Animal Production Research Institute, Shika- Zaria, Nigeria. 2 weeks baseline pre-infection data were collected and the ewes were later divided into two groups of infected and controls. The six animals in the infected group were each orally inoculated with 1200 Fasciola gigantica metacercariae and monitored for a period of 16 weeks. The pathogenic effects of Fasciola gigantica infection began to manifest as of 9 th week post infection through clinical symptoms of bottle jaw, emaciation, depression and pallor of mucus membrane among the infected group. Eggs were demonstrated in faeces of the infected animals at 12 th week post-infection. The pathogenic effect was also evident based on fluke biomass, mean fluke length and width, degree of liver damage, serum AST, ALT, ALP and electrolytes responses. There was an increased level of AST from the 4 th week post-infection indicating greater damage to the liver parenchyma while the levels of ALT began to rise at the 9 th week post -infection among the infected group indicating epithelial damage in the bile ducts. The findings of this study reveals the diagnostic potentials of liver enzymes in the early detection of ovine fasciolosis.
Regulation of Ethylene Biosynthesis in Virus-Infected Tobacco Leaves : II. TIME COURSE OF LEVELS OF INTERMEDIATES AND IN VIVO CONVERSION RATES.

Ethylene production was stimulated severalfold during the hypersensitive reaction of Samsun NN tobacco to tobacco mosaic virus (TMV). Exogenous methionine or S-adenosylmethionine (SAM) did not increase ethylene evolution from healthy or TMV-infected leaf discs, although both precursors were directly available for ethylene production. This indicates that ethylene production is not controlled at the level of methionine concentration or availability, nor at the level of SAM production or concentration. In contrast, 1-aminocyclopropane-1-carboxylic acid (ACC) stimulated ethylene production considerably. Thus, ethylene production is primarily limited at the level of ACC production.The regulation of ethylene production during the hypersensitive reaction to TMV was further studied by determining the time course of the concentrations of methionine, SAM, and ACC, as well as the course of their in vivo conversion rates. Endogenous concentrations of methionine and SAM remained unaffected until late in infection. On the contrary, the peak in ethylene production near the time of local lesion development was preceded by a large increase in ACC production. As a result of this increase, ACC accumulated in the leaf tissue. Only after local lesions became visible, the capacity to convert ACC into ethylene increased severalfold, associated with a sharp decrease in ACC content and a large increase in ethylene production.Ethylene production in tobacco leaves reacting hypersensitively to TMV is thus regulated at the level of both the production of ACC and its conversion to ethylene.
Patency Results of Percutaneous and Surgical Revascularization for Femoropopliteal Arterial Disease

To estimate the patency results of percutaneous transluminal angioplasty and bypass surgery in the treatment of femoropopliteal arterial disease, a Medlars search of the English-language medical literature was performed. Inclusion required that studies 1) report original data, 2) report patency with a life table or Kaplan-Meier analysis with the number at risk or standard errors, 3) define patency as hemodynamic improvement, 4) report the distribution of co variates, and 5) not duplicate other published material. Using a method based on the pro portional-hazards model and the actuarial life-table approach, the results were adjusted for differences in case-mix of the study populations and patency was predicted for subgroups at various levels of risk for failure. The unadjusted pooled life tables yielded five-year pa tencies of 45% (± 2%) for angioplasty, 73% (± 2%) for bypass surgery using a vein graft, and 49% ( ± 3%) for bypass surgery using a polytetrafluoroethylene graft. Adjusted five- year primary patencies after angioplasty varied from 12% to 68%, the best results being for patients with claudication and stenotic lesions. Adjusted five-year primary patencies after surgery varied from 33% to 80%, the best results being for saphenous vein bypass performed for claudication. The authors conclude that pooling life-table data without adjustment for covariates can be misleading. Indication, lesion type, vein graft availability, and site of the distal graft anastomosis need to be considered in predicting patency results of revascular ization for femoropopliteal arterial disease. Key words: arteries, femoral; arteries, popliteal; arteries, transluminal angioplasty; arteries, surgery; review; meta-analysis. (Med Decis Mak ing 1994;14:71-81)
Regulation and Biochemistry of Mouse Molybdo-flavoenzymes

Mouse molybdo-flavoenzymes consist of xanthine oxidoreductase, aldehyde oxidase (AOX1), and two recently identified proteins, AOH1 and AOH2 (aldehyde oxidase homologues 1 and 2). Here we demonstrate that CD-1, C57BL/6, 129/Sv, and other mouse strains synthesize high levels of AOH1 in the liver and AOH2 in the skin. By contrast, the DBA/2 and CBA strains are unique, having a selective deficit in the expression of the AOH1 and AOH2 genes. DBA/2 animals synthesize trace amounts of a catalytically active AOH1 protein. However, relative to CD-1 animals, an over 2 log reduction in the steady-state levels of liver AOH1 mRNA, protein, and enzymatic activity is observed in basal conditions and following administration of testosterone. The DBA/2 mouse represents a unique opportunity to purify AOX1 and compare its enzymatic characteristics to those of the AOH1 protein. The spectroscopy and biochemistry of AOX1 are very similar to those of AOH1 except for a differential sensitivity to the non-competitive inhibitory effect of norharmane. AOX1 and AOH1 oxidize an overlapping set of aldehydes and heterocycles. For most compounds, the substrate efficiency (Vmax/Km) of AOX1 is superior to that of AOH1. Alkylic alcohols and acetaldehyde, the toxic metabolite of ethanol, are poor substrates of both enzymes. Consistent with this, the levels of acetaldehyde in the livers of ethanol administered CD-1 and DBA/2 mice are similar, indicating that neither enzyme is involved in the in vivo biotransformation of acetaldehyde.
Touch-shake: Design and implementation of a physical contact support device for face-to-face communication

In this study we developed the Touch-Shake, which supports physical contact for face-to-face communication. The Touch-Shake has a LED and a speaker, and is shaped like a baton. When each user holds a Touch-Shake and one user touches the body of the other, the LEDs of the Touch-Shakes turn on and the Touch-Shakes output sounds. Additionally, the output sounds and lighting pattern of LEDs vary based on how the user touches the other body, the users' body condition, and the users' physical attributes, which are measured using a capacitive sensor built into the Touch-Shake. The results of an evaluative experiment revealed that the subjects enjoyed physical contact with the Touch-Shake, and they were able to experience rich face-to-face communication.
The impact of operative time on complications after plastic surgery: a multivariate regression analysis of 1753 cases.

BACKGROUND Little evidence within plastic surgery literature supports the precept that longer operative times lead to greater morbidity. OBJECTIVE The authors investigate surgery duration as a determinant of morbidity, with the goal of defining a clinically relevant time for increased risk. METHODS A retrospective chart review was conducted of patients who underwent a broad range of complex plastic surgical procedures (n = 1801 procedures) at UT Southwestern Medical Center in Dallas, Texas, from January 1, 2008 to January 31, 2012. Adjusting for possible confounders, multivariate logistic regression assessed surgery duration as an independent predictor of morbidity. To define a cutoff for increased risk, incidence of complications was compared among quintiles of surgery duration. Stratification by type of surgery controlled for procedural complexity. RESULTS A total of 1753 cases were included in multivariate analyses with an overall complication rate of 27.8%. Most operations were combined (75.8%), averaging 4.9 concurrent procedures. Each hour increase in surgery duration was associated with a 21% rise in odds of morbidity (P < .0001). Compared with the first quintile of operative time (<2.0 hours), there was no change in complications until after 3.1 hours of surgery (odds ratio, 1.6; P = .017), with progressively greater odds increases of 3.1 times after 4.5 hours (P < .0001) and 4.7 times after 6.8 hours (P < .0001). When stratified by type of surgery, longer operations continued to be associated with greater morbidity. CONCLUSIONS Surgery duration is an independent predictor of complications, with a significantly increased risk above 3 hours. Although procedural complexity undoubtedly affects morbidity, operative time should factor into surgical decision making.
Angiographic assessment of cardiac allograft vasculopathy: results of a Consensus Conference of the Task Force for Thoracic Organ Transplantation of the German Cardiac Society

Angiograms of cardiac transplant (HTx) recipients were to be evaluated in a ring experiment and a joint consensus on criteria of angiographic evaluation of coronary arteries of HTx patients was to be reached. Twenty‐four coronary angiograms from 11 hospitals were circulated. One hundred eighty‐eight blinded evaluations were returned. A joint evaluation by six experienced cardiologists was used as reference standard and a consensus evaluation form was developed. Significant lesions (stenosis 75%, 50% in the left main coronary artery) were diagnosed in 10/23 abnormal coronary angiograms (41.7%). Interventional revascularization was recommended in 8/10 (80%). In 21 coronary angiograms distal pruning was found and in 11/21 (52.4%) cases with distal pruning occlusion of at least one peripheral vessel was detected. The best kappa value (0.7) was found for the presence of at least one clinically significant stenosis. Agreement on the site and grade of local stenosis was much less. Some agreement on remodeling was found in assessing diffuse narrowing in the LCA (kappa = 0.371, P < 0.001). The kappa value for peripheral obliteration was 0.331 (P = 0.001). Angiographic evaluation of cardiac allograft vasculopathy, particularly of diffuse and peripheral disease and remodeling, needs standardization. This should be performed in a downward compatible improvement process.
Eight years of surveillance of patients hospitalized with hepatitis: interpretation of data in light of epidemic parenteral drug abuse and availability of testing for hepatitis-associated antigen.

As part of a continuing program of surveillance, 370 patients hospitalized with acute viral hepatitis were grouped epidemiologically and tested for hepatitis-associated antigen (HAA) by a modified immunodiffusion method. HAA was detected in the serum of 54% of the 104 patients believed to have acquired hepatitis through admitted parenteral drug abuse. Patients unaware of (or denying) suspected parenteral exposures were HAA-positive significantly less often (P = .02), although the rate of detection was 40%. Among patients who had had transfusions, two of nine with incubation periods of less than 45 days were HAA-positive, but the average incubation period of HAA-positive cases, 92 days, was 21 days longer than that of HAA-negative cases (P < .005). Hospital personnel accounted for 7% of the hospitalized cases, and although few could identify a specific parenteral exposure, 65% were HAA-positive. The proportion of all patients hospitalized with hepatitis who acknowledged parenteral drug abuse rose from an average of 4% in the years 1963-1966 to 30% in 1967-1971, a striking increase that may have contributed to urban endemicity of HAA-positive hepatitis.
Digital Decoupling and Disentangling: Towards Design for Romantic Break Up

Romantic relationships are often facilitated through digital technologies, such as social networking sites and communication services. They are also facilitated through "digital possessions", such as messages sent to mobile devices and photos shared through social media. When individuals break up, digitally disconnecting can be facilitated by using those digital technologies and managing or curating these digital possessions. This research explores the break up stories of 13 individuals aged between 18 and 52. The aim of this work is to inform the design of systems focused on supporting individuals to decouple and disentangle digitally in the wake of a break up. Four areas of interest emerged from the data: communication, using digital possessions, managing digital possessions, and experiences of technology. Opportunities for design were identified in decoupling and disentangling, and designing around guilt.
Risk factors and outcomes in “well-selected” vaginal breech deliveries: a retrospective observational study

Abstract Objective: To assess risk factors for adverse perinatal and neonatal outcomes in “well-selected” singleton vaginal breech deliveries at term. Methods: During the time span from January 2008 up to April 2015 a total of 786 singleton term breech deliveries with a planned vaginal delivery were identified in a retrospective observational study at Helsinki University Central Hospital, Finland. The study’s end point was a composite of adverse perinatal and neonatal outcomes. Infants with an adverse outcome were compared to all spontaneous singleton vaginal breech deliveries with normal perinatal and neonatal outcomes. A multivariate logistic regression model was used to analyze associations between adverse neonatal outcomes and several variables. The secondary outcome was the severe morbidity rate according to the criteria of the term breech trial. Results: An adverse neonatal outcome was recorded for 38 (4.8%) infants. According to the study the second delivery stage lasting <40 min [adjusted odds ratio (aOR): 0.34, 95% confidence interval (95% CI): 0.15–0.79] was associated with lower odds and had a protective effect against adverse outcomes. Epidural anesthesia (aOR: 2.88, 95% CI: 1.08–7.70) was associated with higher adverse outcomes. The incidence rate of severe morbidity was 1.3% (10/787). Conclusion: Adverse neonatal outcomes in well-selected breech deliveries are associated with a prolonged second delivery stage lasting >40 min and with epidural anesthesia.
Evidence of small-bowel involvement in hereditary hemorrhagic telangiectasia: a capsule-endoscopic study.

BACKGROUND AND STUDY AIMS Hereditary hemorrhagic telangiectasia (HHT) is an autosomal-dominant vascular disorder leading to telangiectases and arteriovenous malformations of the skin, mucosa, and viscera. Telangiectases in the upper gastrointestinal tract are known, but data regarding possible small-bowel involvement are scarce due to the technical difficulty of exploring the entire gastrointestinal tract. The aim of the present study was to use capsule endoscopy (CE) to determine the prevalence of small-bowel telangiectases in HHT patients. PATIENTS AND METHODS From December 2001 to September 2002, 20 consecutive adult HHT patients at an interdepartmental HHT center were prospectively evaluated. All patients underwent esophagogastroduodenoscopy (EGD) followed by CE within 24 h. The telangiectases were scored according to commonly accepted criteria by two endoscopists and two observers of the video-capsule images, who were blinded to each other's findings. RESULTS EGD revealed gastric telangiectases in 15 of the 20 patients (75 %), while CE demonstrated small-bowel involvement in 10 of 18 patients (56 %; images were not recorded for two patients due to battery failure). No preferential site for telangiectasia was found between the jejunum and the terminal ileum. All patients who were positive on CE were also found to have gastric involvement at EGD. Patients with small-bowel telangiectases were significantly older than those without (62.5 years vs. 45 years; P < 0.02). CONCLUSIONS This study established a 56 % prevalence of small-bowel telangiectases in patients with HHT. This new endoscopic technique will probably change the etiological diagnosis of occult bleeding in HHT patients (which is too often attributed only to epistaxis) and may also be able to alter treatment strategies in HHT patients with gastrointestinal bleeding.
Melatonin reduces lung oxidative stress in patients with chronic obstructive pulmonary disease: a randomized, double‐blind, placebo‐controlled study

Abstract: Chronic obstructive pulmonary disease (COPD), a major cause of death and disability, is attributed to an abnormal inflammatory response by the lungs to noxious substances, primarily from cigarette smoke. Although oxidative stress is regarded as central to the pathogenesis of COPD, very few studies have examined the effects of antioxidants in this condition. This was a randomized, double‐blind, placebo‐controlled study on the effects of melatonin in COPD. Thirty‐six consecutive patients with clinically stable moderate to very severe COPD (30 men; mean ± S.D. = 66.6 ± 7.8 yr) were randomized to receive 3 mg melatonin (N = 18) or placebo for 3 months. Oxidative stress was evaluated by 8‐isoprostane levels in exhaled breath condensate at baseline (T0) and after one (T1), two (T2), and three months (T3) of treatment. Additionally, exhaled breath condensate levels of IL‐8, dyspnea severity (Medical Research Council scale), lung function (spirometry), and functional exercise capacity (six min walk test) were compared at baseline and after treatment. Patients receiving melatonin showed a decrease in 8‐isoprostane (T0: mean ± S.E.M. = 20.41 ± 2.92 pg/mL; T1: 18.56 ± 2.68 pg/mL; T2: 12.68 ± 2.04 pg/mL; T3: 12.70 ± 2.18 pg/mL; P = 0.04; repeated measures ANOVA) with significant differences from baseline after 2 (P = 0.03) and 3 months (P = 0.01). Dyspnea was improved by melatonin (P = 0.01), despite no significant changes in lung function or exercise capacity. Placebo‐treated patients, but not those who were given melatonin, showed an increase in IL‐8 (P = 0.03). In summary, melatonin administration reduced oxidative stress and improved dyspnea in COPD. Further studies are necessary to determine the potential role for melatonin in the long‐term management of these patients.
Interleukin-5 (IL-5) Augments the Progression of Liver Fibrosis by Regulating IL-13 Activity

ABSTRACT Eosinophils are frequently found in increased numbers in a variety of chronic fibrotic diseases; however, their role in the development of hepatic fibrosis has not been dissected in vivo. Here, we used interleukin-5 (IL-5) knockout (KO) mice to determine whether eosinophils contribute to the progressive liver fibrosis that develops in response to chronic Schistosoma mansoni infection. Although infection intensities were similar in C57BL/6 and IL-5 KO mice, the average size of granulomas was significantly smaller in both acutely and chronically infected IL-5 KO mice. Their granulomas were also completely devoid of eosinophils. In addition, the knockout mice displayed over a 40% reduction in hepatic fibrosis by week 16 postinfection. The reduced fibrosis was associated with increased production of the antifibrotic cytokine gamma interferon. Moreover, although IL-13 production did not decrease consistently in the absence of IL-5, IL-13-triggered responses were substantially reduced in the granulomatous tissues. This was confirmed by analyzing the expression of several genes associated with alternative macrophage activation, including arginase 1, Fizz-1, and YM-1. Importantly, all of these IL-13-regulated genes have been linked with the mechanisms of wound healing and fibrosis. In addition to IL-5 polarizing the antigen-specific CD4+ Th2 cell response, we found that granuloma eosinophils were themselves a significant source of IL-13. Thus, by producing profibrotic mediators and polarizing the Th2 response, these findings illustrate both direct and indirect roles for eosinophils and IL-5 in the pathogenesis of schistosomiasis-induced liver fibrosis. Thus, inhibiting the activity of IL-5 or eosinophils may prove effective for a variety of chronic fibrotic diseases.