Miracle-dz/UniFAR-FTUs huggingface dataset:
RNAi targeting multiple cell adhesion molecules reduces immune cell recruitment and vascular inflammation after myocardial infarction

Nanoparticles deliver siRNA for multigene silencing of endothelial cell adhesion molecules, which dampens leukocyte recruitment in atherosclerosis and myocardial infarction in mice. Knocking down adhesion, knocking out inflammation Cells that are central to inflammation lodge in damaged or fatty regions of the vessels (called plaques) by “feeling out” the vessel surface. Neutrophils and monocytes first “roll” along the wall, then firmly plant themselves at an ideal site, and lastly pass through the cells lining the blood vessel: the endothelial cells. This recruitment and transmigration process is mediated by surface receptors called cell adhesion molecules (CAMs). Sager et al. developed a nanomedicine approach to preventing such inflammatory cell adhesion and exacerbation of plaques, by transiently knocking down five different CAMs simultaneously. The authors delivered small interfering RNA (siRNA) targeting the CAMs inside nanoparticles that had been optimized to reach endothelial cells. The five siRNAs reduced leukocyte recruitment to atherosclerotic plaques in mice that were engineered to develop certain features of human atherosclerosis. In the same mice, the siRNAs also attenuated inflammation after myocardial infarction—the equivalent of a heart attack. Current therapies for atherosclerosis and cardiovascular disease do not target inflammatory cells, and this multipronged siRNA-based nanomedicine approach could complement existing options to prevent heart disease from worsening. Myocardial infarction (MI) leads to a systemic surge of vascular inflammation in mice and humans, resulting in secondary ischemic complications and high mortality. We show that, in ApoE−/− mice with coronary ligation, increased sympathetic tone up-regulates not only hematopoietic leukocyte production but also plaque endothelial expression of adhesion molecules. To counteract the resulting arterial leukocyte recruitment, we developed nanoparticle-based RNA interference (RNAi) that effectively silences five key adhesion molecules. Simultaneously encapsulating small interfering RNA (siRNA)–targeting intercellular cell adhesion molecules 1 and 2 (Icam1 and Icam2), vascular cell adhesion molecule 1 (Vcam1), and E- and P-selectins (Sele and Selp) into polymeric endothelial-avid nanoparticles reduced post-MI neutrophil and monocyte recruitment into atherosclerotic lesions and decreased matrix-degrading plaque protease activity. Five-gene combination RNAi also curtailed leukocyte recruitment to ischemic myocardium. Therefore, targeted multigene silencing may prevent complications after acute MI.
Targeting factor D of the alternative complement pathway reduces geographic atrophy progression secondary to age-related macular degeneration

The phase 2 MAHALO clinical trial shows that lampalizumab reduces geographic atrophy secondary to age-related macular degeneration and implicates complement dysregulation in disease pathogenesis. Illuminating a new treatment for macular degeneration Geographic atrophy secondary to age-related macular degeneration is a major cause of vision loss for which there is no treatment. Yaspan et al. now report the results of the MAHALO phase 2 randomized, controlled trial that evaluated lampalizumab in patients with geographic atrophy secondary to age-related macular degeneration. Lampalizumab is a specific inhibitor of complement factor D, a pivotal regulator of the alternative complement pathway. The MAHALO study met its primary efficacy endpoint with a 20% reduction in lesion area progression compared to sham control with monthly lampalizumab treatment. Moreover, lampalizumab showed an acceptable safety profile. A more substantial monthly treatment benefit of 44% reduction in geographic atrophy progression versus sham control was observed in a subgroup of patients who were complement factor I risk-allele carriers. Geographic atrophy is an advanced form of age-related macular degeneration (AMD) and a leading cause of vision loss for which there are no approved treatments. Genetic studies in AMD patients have implicated dysregulation of the alternative complement pathway in the pathogenesis of geographic atrophy. Lampalizumab is a potential therapeutic that targets complement factor D, a pivotal activator of the alternative complement pathway. The MAHALO phase 2 clinical trial was a multicenter, randomized, controlled study that evaluated lampalizumab administered by intravitreal injection monthly (n = 42) and every other month (n = 41) versus sham control (n = 40) in patients with geographic atrophy secondary to AMD. The primary endpoint was the mean change in lesion area from baseline to month 18 as measured by fundus autofluorescence. Specific AMD-associated genetic polymorphisms were also analyzed. The MAHALO study met its primary efficacy endpoint with an acceptable safety profile; monthly lampalizumab treatment demonstrated a 20% reduction in lesion area progression versus sham control [80% confidence interval (CI), 4 to 37%]. A more substantial monthly treatment benefit of 44% reduction in geographic atrophy area progression versus sham control (95% CI, 15 to 73%) was observed in a subgroup of complement factor I (CFI) risk-allele carriers (57% of the patients analyzed were CFI risk-allele carriers). The MAHALO study shows a potential treatment effect in patients with geographic atrophy and supports therapeutic targeting of the alternative complement pathway for treating AMD pathogenesis.
Familial autoinflammation with neutrophilic dermatosis reveals a regulatory mechanism of pyrin activation

A mutation in pyrin that disrupts regulation leads to autoinflammatory disease. Guarding inflammation The innate immune system is hard-wired to protect people from infection. However, mutations in these protective genes can lead to uncontrolled inflammation, resulting in autoinflammatory disease. Now, Masters et al. describe a family with an autoinflammatory disease caused by a previously unreported mutation in pyrin. This mutation disrupts pyrin regulation and mimics the effect of pathogen sensing by pyrin, leading to proinflammatory interleukin-1β (IL-1β) production. Indeed, targeting IL-1β resolved disease in one patient. These data suggest that pyrin is regulated through a guard-like mechanism, which guards against autoinflammation in humans. Pyrin responds to pathogen signals and loss of cellular homeostasis by forming an inflammasome complex that drives the cleavage and secretion of interleukin-1β (IL-1β). Mutations in the B30.2/SPRY domain cause pathogen-independent activation of pyrin and are responsible for the autoinflammatory disease familial Mediterranean fever (FMF). We studied a family with a dominantly inherited autoinflammatory disease, distinct from FMF, characterized by childhood-onset recurrent episodes of neutrophilic dermatosis, fever, elevated acute-phase reactants, arthralgia, and myalgia/myositis. The disease was caused by a mutation in MEFV, the gene encoding pyrin (S242R). The mutation results in the loss of a 14-3-3 binding motif at phosphorylated S242, which was not perturbed by FMF mutations in the B30.2/SPRY domain. However, loss of both S242 phosphorylation and 14-3-3 binding was observed for bacterial effectors that activate the pyrin inflammasome, such as Clostridium difficile toxin B (TcdB). The S242R mutation thus recapitulated the effect of pathogen sensing, triggering inflammasome activation and IL-1β production. Successful therapy targeting IL-1β has been initiated in one patient, resolving pyrin-associated autoinflammation with neutrophilic dermatosis. This disease provides evidence that a guard-like mechanism of pyrin regulation, originally identified for Nod-like receptors in plant innate immunity, also exists in humans.
Do higher doses of carbimazole improve remission in Graves' disease?

The aim of this study was to determine whether a course of carbimazole therapy in higher than normal doses could improve remission rates in Graves' disease, 77 patients were randomly allocated to one of two treatment groups. Group 1 ( n = 33) received a 12-month course of 60 mg/day carbimazole. Group 2 ( n = 44) received 45 mg/day for the first month, 30 mg/day for the second month, and 20 mg/day for the remaining 10 months. All patients were started on T3 between 2 and 4 months after commencing therapy, to maintain euthyroidism. After carbimazole/T3 therapy was withdrawn, patients were followed for either 12 months or until they relapsed. A total of 14 patients (five Group 1, nine Group 2) were withdrawn from the study. There was no significant difference in mean thyroid hormone levels between the two treatment groups during treatment. TT4 concentrations fell significantly faster during the first 4 weeks of treatment in Group 1 patients. Of the 63 patients who completed the study, 30 relapsed and 33 remained in remission. Of those who relapsed, 10 (33%) were from Group 1 and 20 (67%) from Group 2. Of those in remission, 18 (54%) were from Group 1 and 15 (45%) from Group 2. High doses of carbimazole were associated with few adverse side-effects and an improved remission rate.
A Spatial Contextual Postclassification Method for Preserving Linear Objects in Multispectral Imagery

Classification of remote sensing multispectral data is important for segmenting images and thematic mapping and is generally the first step in feature extraction. Per-pixel classification, based on spectral information alone, generally produces noisy classification results. The introduction of spatial information has been shown to be beneficial in removing most of this noise. Probabilistic label relaxation (PLR) has proved to be advantageous using second-order statistics; here, we present a modified contextual probabilistic relaxation method based on imposing directional information in the joint probability with third-order statistics. The proposed method was tested in synthetic images and real images; the results are compared with a “Majority” algorithm and the classical PLR method. The proposed third-order method gives the best results, both visually and numerically.
An Audit of Vaginal Hysterectomies in Enugu, Nigeria

Background: There is scanty data on vaginal hysterectomy in Nigeria Objective: To determine the rate, indications and complications of vaginal hysterectomy as seen in a Nigerian tertiary care centre. Methods: A retrospective review of vaginal hysterectomies performed at the University of Nigeria Teaching Hospital, Enugu, Nigeria, over a six year period (1995-2000). Results: There were 13 vaginal hysterectomies per 1000 gynaecological operations. Genital prolapse was the only indication for the 84 vaginal hysterectomies performed during the study period. Moderate to severe intrapelvic adhesions were found in 4 (4.8%) of the patients. The uterine size was less than 12 weeks gestation size in all the 84(100%) cases. Incidental operations were anterior colporrhaphy in all the 84 (100%) cases and posterior colporrhaphy in 25 (29.8%) of the subjects. Bilateral oophorectomy was done in 5 (6.0%) and unilateral oophorectomy in 3 (3.6%) of the women. Complications were recorded in 15 women, giving a complication rate of 17.9%. Urinary tract infection was the commonest complication. Conclusion: Vaginal hysterectomy rate in Enugu, Nigeria is lower and the indications for the operation more limited than in the United States of America and Western Europe. Key Words: Vaginal hysterectomy, rate, indications, complications, Nigeria [Trop J Obstet Gynaecol, 2004;21:58-60].
Using DInSAR to Separate Surface and Subsurface Features

We report on an investigation into the use of differential interferometric synthetic aperture radar (SAR) (DInSAR) for the discrimination between surface and subsurface features in a soil, undertaken at the Ground-Based SAR Microwave Measurement Facility. A temporal sequence of C-band VV SAR images of a drying soil containing a buried target was collected. While the phase record of the signal identified with the soil return showed almost no variation, in stark contrast, the phase from the buried target showed a strongly linear change with time. A model is presented, which describes the observed phase changes in terms of retardation of the signal by the soil dielectric properties, which are dependent upon the moisture content. The model confirms a strongly linear relationship between phase and volumetric soil moisture. The linearity promises to greatly simplify any exploitation scheme, and such a DInSAR scheme would be applicable at large standoff distances from airborne and spaceborne platforms, in contrast to current subsurface techniques which rely on close-in measurement to spatially isolate returns vertically in backscatter.
Coherent Change Detection Using Passive GNSS-Based BSAR: Experimental Proof of Concept

This paper presents proof-of-concept methods and results on a passive synthetic aperture radar for surface change monitoring. The bistatic topology comprises navigation satellites (such as Global Positioning System, GLObal Navigation Satellite System (GLONASS), Galileo, or Beidou) as transmitters of opportunity and a fixed receiver on the ground. Surface monitoring is to be provided through coherent change detection. An experimental test bed built to confirm the concept of the system is described, and the appropriate experimental program is presented. Preliminary signal processing algorithms for change detection are derived. Experimentally measured changes are compared to the theoretical predictions, and the obtained results are discussed.
Estimation of polio infection prevalence from environmental surveillance data

Close monitoring of virus shed into sewage systems allows quantitative surveillance of a polio outbreak. Keeping an eye on polio As the eyes are a mirror of the soul, a city’s sewage is a reflection of its people’s health. Berchenko et al. take advantage of a natural experiment in southern Israel to quantify this relationship for polio. By measuring virus shed into sewage waste in cities in which a known number of people received a live polio vaccine, the authors created tools that can be used to monitor polio incidence in other cities. Thus, virus levels in sewage waste can give an early warning of the reappearance of viral disease or verify its absence. A major obstacle to eradicating polio is that poliovirus from endemic countries can be reintroduced to polio-free countries. Environmental surveillance (ES) can detect poliovirus from sewage or wastewaters samples, even in the absence of patients with paralysis. ES is underused, in part because its sensitivity is unknown. We used two unique data sets collected during a natural experiment provided by the 2013 polio outbreak in Israel: ES data from different locations and records of supplemental immunization with the live vaccine. Data from the intersecting population between the two data sets (covering more than 63,000 people) yielded a dose-dependent relationship between the number of poliovirus shedders and the amount of poliovirus in sewage. Using a mixed-effects linear regression analysis of these data, we developed several quantitative tools, such as (i) ascertainment of the number of infected individuals from ES data for application during future epidemics elsewhere, (ii) evaluation of the sensitivity of ES, and (iii) determination of the confidence level of the termination of poliovirus circulation after an outbreak. These results will be valuable in monitoring future outbreaks with ES, and this approach could be used to certify poliovirus elimination or to validate the need for more containment efforts.
Nodding syndrome may be an autoimmune reaction to the parasitic worm Onchocerca volvulus

Patients with nodding syndrome have autoantibodies to leiomodin-1 that are neurotoxic and cross-react with proteins of the parasitic worm Onchocerca volvulus. Linking parasitic infection to autoimmune epilepsy Nodding syndrome is a unique seizure disorder affecting children in parts of East Africa. The cause of nodding syndrome has been an enigma, although an epidemiological association with the parasite Onchocerca volvulus has been established. Johnson et al. demonstrate that patients with nodding syndrome have autoantibodies to leiomodin-1 that are neurotoxic in vitro and that leiomodin-1 is expressed in regions of the brain affected during disease. Leiomodin-1 antibodies cross-react with O. volvulus proteins, linking the parasite to the autoantibody. Thus, nodding syndrome may be an autoimmune epilepsy initiated by a parasitic infection and may be preventable by treatment with antiparasitic strategies such as the drug ivermectin. Nodding syndrome is an epileptic disorder of unknown etiology that occurs in children in East Africa. There is an epidemiological association with Onchocerca volvulus, the parasitic worm that causes onchocerciasis (river blindness), but there is limited evidence that the parasite itself is neuroinvasive. We hypothesized that nodding syndrome may be an autoimmune-mediated disease. Using protein chip methodology, we detected autoantibodies to leiomodin-1 more abundantly in patients with nodding syndrome compared to unaffected controls from the same village. Leiomodin-1 autoantibodies were found in both the sera and cerebrospinal fluid of patients with nodding syndrome. Leiomodin-1 was found to be expressed in mature and developing human neurons in vitro and was localized in mouse brain to the CA3 region of the hippocampus, Purkinje cells in the cerebellum, and cortical neurons, structures that also appear to be affected in patients with nodding syndrome. Antibodies targeting leiomodin-1 were neurotoxic in vitro, and leiomodin-1 antibodies purified from patients with nodding syndrome were cross-reactive with O. volvulus antigens. This study provides initial evidence supporting the hypothesis that nodding syndrome is an autoimmune epileptic disorder caused by molecular mimicry with O. volvulus antigens and suggests that patients may benefit from immunomodulatory therapies.
Analgesia after feline ovariohysterectomy under midazolam-medetomidine-ketamine anaesthesia with buprenorphine or butorphanol, and carprofen or meloxicam: a prospective, randomised clinical trial

One hundred female cats undergoing routine ovariohysterectomy under midazolam-medetomidine-ketamine anaesthesia were included in a blinded, randomised, prospective clinical study to compare postoperative analgesia produced by four analgesic drug combinations given preoperatively (n = 25 per group). A secondary aim was to assess the effects in kittens and pregnant animals. Buprenorphine 180 µg/m2 or butorphanol 6 mg/m2 were given with either carprofen 4 mg/kg (groups BUPC and BUTC, respectively) or meloxicam 0.3 mg/kg (groups BUPM or BUTM, respectively). Medetomidine was not antagonised. A simple, descriptive scale (SDS; 0–4), a dynamic and interactive visual analogue scale (DIVAS; 0–100 mm) and mechanical nociceptive thresholds (MT; 2.5-mm diameter probe) were used to evaluate postoperative pain. All pain scores were low (DIVAS <10 mm, SDS <2 and MT >10 N) and there were no significant differences between the groups. It was concluded that all protocols provided adequate analgesia and when used with midazolam-medetomidine-ketamine are effective for routine feline ovariohysterectomy.
Vaccination of dogs in an African city interrupts rabies transmission and reduces human exposure

A citywide dog vaccination effort in Chad reduced the local spread of rabies from dogs to humans. Stemming the spread of rabies Rabies is still a problem in some developing countries. The authors examine the impact of two previously conducted vaccination campaigns that vaccinated about 70% of dogs against rabies in N’Djaména, the capital city of Chad. Transmission modeling and phylodynamic analysis supported the idea that the sequential vaccination campaigns reduced dog-to-dog and dog-to-human rabies transmission. A phylogenetic analysis suggested that post-campaign reintroduction of rabies to N’Djaména may have occurred due to unvaccinated dogs in regions surrounding the city, rather than ongoing transmission within immunized areas in the city. Thus, mass vaccination efforts may be effective tools to stem rabies incidence in regions still afflicted by this fatal disease. Despite the existence of effective rabies vaccines for dogs, dog-transmitted human rabies persists and has reemerged in Africa. Two consecutive dog vaccination campaigns took place in Chad in 2012 and 2013 (coverage of 71% in both years) in the capital city of N’Djaména, as previously published. We developed a deterministic model of dog-human rabies transmission fitted to weekly incidence data of rabid dogs and exposed human cases in N’Djaména. Our analysis showed that the effective reproductive number, that is, the number of new dogs infected by a rabid dog, fell to below one through November 2014. The modeled incidence of human rabies exposure fell to less than one person per million people per year. A phylodynamic estimation of the effective reproductive number from 29 canine rabies virus genetic sequences of the viral N-protein confirmed the results of the deterministic transmission model, implying that rabies transmission between dogs was interrupted for 9 months. However, new dog rabies cases appeared earlier than the transmission and phylodynamic models predicted. This may have been due to the continuous movement of rabies-exposed dogs into N’Djaména from outside the city. Our results show that canine rabies transmission to humans can be interrupted in an African city with currently available dog rabies vaccines, provided that the vaccination area includes larger adjacent regions, and local communities are informed and engaged.
SAR Doppler Ambiguity Resolver Based on Entropy Minimization

The determination of Doppler ambiguity number (DAN) is indispensable for the generation of high-quality synthetic aperture radar (SAR) images. An incorrect DAN leads to lower image signal-to-noise ratio and degradation in the system impulse response function. Based on the relationship between DAN errors and the image quality, a novel DAN estimation algorithm named image-quality-based Doppler ambiguity resolver is presented. In the proposed algorithm, the DAN-dependent linear range cell migration correction and DAN-dependent azimuth compression are carried out in subscenes to obtain 2-D compressed SAR images, which are further employed to estimate DAN via minimizing the entropy. The presented algorithm is more robust than conventional methods to cope with demands of both low- and high-contrast scene applications. In addition, the approach is computationally efficient because it can be properly applied to segments of range-compressed data in small size and only a few sets of short fast Fourier transforms are required. Finally, experiments over real data of airborne X-band and spaceborne C-band are carried out to demonstrate the performance of the proposed approach.