Miracle-dz/UniFAR-FTUs huggingface dataset:
HIV-associated Hodgkin lymphoma.

PURPOSE OF REVIEW The focus of this review is on the current knowledge on epidemiology, pathology and treatment of HIV-associated Hodgkin lymphoma (HIV-HL). RECENT FINDINGS Among non-AIDS-defining cancers, an increased risk of Hodgkin lymphoma was recently observed. However, the relationship between HIV infection, AIDS and Hodgkin lymphoma is still unclear. SUMMARY In the highly active antiretroviral therapy era, HIV-infected people seem to be at increased risk of Hodgkin lymphoma than in first years of the epidemic. In these persons with improved immunity, increased CD4+ T cells provide antiapoptotic pathways and mechanisms for immune escape by tumor cells, as occurs in classic Hodgkin lymphoma among people without AIDS. Several studies have documented a significant difference in the distribution of Hodgkin lymphoma subtypes in HIV-infected persons as compared with Hodgkin lymphoma in HIV-uninfected population. HIV-HL exhibits special features related to the cellular background and the abundance of the neoplastic cell population, respectively. The fact that latent membrane protein 1 is expressed in virtually all HIV-HL cases suggests that Epstein-Barr virus plays an etiological role in the pathogenesis of HIV-HL. Recent advances in combined therapies, which are beginning to show promise in the treatment of this HIV-associated disorder, are discussed.
The Contribution of Alu Elements to Mutagenic DNA Double-Strand Break Repair

Alu elements make up the largest family of human mobile elements, numbering 1.1 million copies and comprising 11% of the human genome. As a consequence of evolution and genetic drift, Alu elements of various sequence divergence exist throughout the human genome. Alu/Alu recombination has been shown to cause approximately 0.5% of new human genetic diseases and contribute to extensive genomic structural variation. To begin understanding the molecular mechanisms leading to these rearrangements in mammalian cells, we constructed Alu/Alu recombination reporter cell lines containing Alu elements ranging in sequence divergence from 0%-30% that allow detection of both Alu/Alu recombination and large non-homologous end joining (NHEJ) deletions that range from 1.0 to 1.9 kb in size. Introduction of as little as 0.7% sequence divergence between Alu elements resulted in a significant reduction in recombination, which indicates even small degrees of sequence divergence reduce the efficiency of homology-directed DNA double-strand break (DSB) repair. Further reduction in recombination was observed in a sequence divergence-dependent manner for diverged Alu/Alu recombination constructs with up to 10% sequence divergence. With greater levels of sequence divergence (15%-30%), we observed a significant increase in DSB repair due to a shift from Alu/Alu recombination to variable-length NHEJ which removes sequence between the two Alu elements. This increase in NHEJ deletions depends on the presence of Alu sequence homeology (similar but not identical sequences). Analysis of recombination products revealed that Alu/Alu recombination junctions occur more frequently in the first 100 bp of the Alu element within our reporter assay, just as they do in genomic Alu/Alu recombination events. This is the first extensive study characterizing the influence of Alu element sequence divergence on DNA repair, which will inform predictions regarding the effect of Alu element sequence divergence on both the rate and nature of DNA repair events.
The retromer complex – endosomal protein recycling and beyond

Summary The retromer complex is a vital element of the endosomal protein sorting machinery that is conserved across all eukaryotes. Retromer is most closely associated with the endosome-to-Golgi retrieval pathway and is necessary to maintain an active pool of hydrolase receptors in the trans-Golgi network. Recent progress in studies of retromer have identified new retromer-interacting proteins, including the WASH complex and cargo such as the Wntless/MIG-14 protein, which now extends the role of retromer beyond the endosome-to-Golgi pathway and has revealed that retromer is required for aspects of endosome-to-plasma membrane sorting and regulation of signalling events. The interactions between the retromer complex and other macromolecular protein complexes now show how endosomal protein sorting is coordinated with actin assembly and movement along microtubules, and place retromer squarely at the centre of a complex set of protein machinery that governs endosomal protein sorting. Dysregulation of retromer-mediated endosomal protein sorting leads to various pathologies, including neurodegenerative diseases such as Alzheimer disease and spastic paraplegia and the mechanisms underlying these pathologies are starting to be understood. In this Commentary, I will highlight recent advances in the understanding of retromer-mediated endosomal protein sorting and discuss how retromer contributes to a diverse set of physiological processes.
Effect of the natural sweetener, steviol glycoside, on cardiovascular risk factors: A systematic review and meta-analysis of randomised clinical trials

Introduction Many different dietary supplements are currently marketed for the management of hypertension and diabetes, but the evidence for effectiveness is mixed. The objective of this systematic review was to critically appraise and evaluate the evidence for effectiveness of steviol glycosides (stevioside and rebaudioside A) on cardiovascular risk factors, using data from randomised clinical trials (RCTs). Methods Electronic searches were conducted in Medline, Embase, Amed, Cinahl and The Cochrane Library. We also searched Google Scholar, and hand searched the bibliography of retrieved full texts. The reporting quality of included studies was assessed using the Cochrane criteria. Two reviewers independently determined the eligibility, assessed the reporting quality, and extracted the data. Results Nine studies with a total of 756 participants were included. There was a variation in the reporting quality of included studies. Meta-analysis revealed a non-significant difference in systolic blood pressure between steviol glycoside and placebo, mean difference (MD): −2.98 mm Hg (−6.23 to 0.27). Significant reductions in diastolic blood pressure and fasting blood glucose were observed. There was no significant effect on blood lipid profile. Heterogeneity was significant. Adverse events included abdominal fullness, epigastric pain, and dizziness. Conclusion The evidence from published RCTs suggests that stevioside may generate reductions in blood pressure and fasting blood glucose. The sizes of the effects are small, and the substantial heterogeneity limits the robustness of any conclusions. Rebaudioside A does not appear to have any significant effects on blood pressure or cardiovascular risk factors. Available clinical trials vary in design and reporting quality, and some are characterised by inadequate sample sizes. In addition, the participants in most of the trials have high cardiovascular risk. Further clinical trials and regulatory assessments are warranted.
Review of Stroke Thrombolytics

The cornerstone of acute ischemic stroke treatment relies on rapid clearance of an offending thrombus in the cerebrovascular system. There are various drugs and different methods of assessment to select patients more likely to respond to treatment. Current clinical guidelines recommend the administration of intravenous alteplase (following a brain noncontract CT to exclude hemorrhage) within 4.5 hours of stroke onset. Because of the short therapeutic time window, the risk of hemorrhage, and relatively limited efficacy of alteplase for large clot burden, research is ongoing to find more effective and safer reperfusion therapy, as well as focussing on refinement of patient selection for acute reperfusion treatment. Studies using advanced imaging (incorporating perfusion CT or diffusion/perfusion MRI) may allow us to use thrombolytics, or possibly endovascular therapy, in an extended time window. Recent clinical trials have suggested that Tenecteplase, used in conjunction with advanced imaging selection, resulted in more effective reperfusion than alteplase, which translated into increased clinical benefit. Studies using Desmoteplase have suggested its potential benefit in a sub-group of patients with large artery occlusion and salveageable tissue, in an extended time window. Other ways to improve acute reperfusion approaches are being actively explored, including endovascular therapy, and the enhancement of thrombolysis by ultrasound insonation of the clot (sono-thrombolysis).
Environmental gradients structure Daphnia pulex × pulicaria clonal distribution

The rarity of eukaryotic asexual reproduction is frequently attributed to the disadvantage of reduced genetic variation relative to sexual reproduction. However, parthenogenetic lineages that evolved repeatedly from sexual ancestors can generate regional pools of phenotypically diverse clones. Various theories to explain the maintenance of this genetic diversity as a result of environmental and spatial heterogeneity [frozen niche variation (FNV), general‐purpose genotype] are conceptually similar to community ecological explanations for the maintenance of regional species diversity. We employed multivariate statistics common in community ecological research to study population genetic structure in the freshwater crustacean, Daphnia pulex × pulicaria. This parthenogenetic hybrid arose repeatedly from sexual ancestors. Daphnia pulex × pulicaria populations harboured substantial genetic variation among populations and the clonal composition at each pond corresponded to nutrient levels and invertebrate predator densities. The interclonal selection process described by the FNV hypothesis likely structured our D. pulex × pulicaria populations.
A Subtraction Mechanism of Temporal Coding in Cerebellar Cortex

The temporally specific learning displayed by the cerebellum facilitates mechanistic analysis of neural timing and temporal coding. We report evidence for a subtraction-like mechanism of temporal coding in cerebellar cortex in which activity in a subset of granule cells specifically codes the interval between the offset of two mossy fiber inputs. In a large-scale cerebellar simulation, cessation of one of two ongoing mossy fiber inputs produces a robust temporal code in the population of granule cells. This activity supports simulation learning in response to temporal patterns of stimuli, even when those same stimuli do not support learning when presented individually. Using stimulation of mossy fiber inputs to the cerebellum as training stimuli in rabbits, we confirmed these unusual predictions in a cerebellum-dependent form of learning. Analysis of the simulations reveals a specific working hypothesis for this temporal subtraction process that involves interactions between granule cells and the inhibitory Golgi cells. The results suggest how feedforward inhibition, such as that present in the cerebellar cortex, can contribute to temporal coding.
The Helicobacter pylori J99 jhp0106 Gene, under the Control of the CsrA/RpoN Regulatory System, Modulates Flagella Formation and Motility

CsrA has been shown to positively control the expression of flagella-related genes, including flaA and flaB, through regulating expression of an alternative sigma factor RpoN in Helicobacter pylori J99. Here, we aimed to characterize the CsrA regulatory system by comparative transcriptomic analysis carried out with RNA-seq on strain J99 and a csrA mutant. Fifty-three genes in the csrA mutant were found to be differentially expressed compared with the wild-type. Among CsrA-regulated genes, jhp0106, with unclear function, was found located downstream of flaB in the J99 genome. We hypothesized that flaB-jhp0106 is in an operon under the control of RpoN binding to the flaB promoter. The RT-qPCR results showed the expression of jhp0106 was decreased 76 and 92% in the csrA and rpoN mutants, respectively, compared to the wild-type. Moreover, mutations of the RpoN binding site in the flaB promoter region resulted in decreased expression of flaB and jhp0106 and deficient motility. Three-dimensional structure modeling results suggested that Jhp0106 was a glycosyltransferase. The role of jhp0106 in H. pylori was further investigated by constructing the jhp0106 mutant and revertant strains. A soft-agar motility assay and transmission electron microscope were used to determine the motility and flagellar structure of examined strains, and the results showed the loss of motility and flagellar structure in jhp0106 mutant J99. In conclusion, we found jhp0106, under the control of the CsrA/RpoN regulatory system, plays a critical role in H. pylori flagella formation.
Made to Fit: How Practices Vary as They Diffuse

We extend research on the diffusion of corporate practices by providing a framework for studying practice variation during diffusion processes. Specifically, we theorize about how population-level mechanisms of diffusion link with organization-level mechanisms of implementation that lead to the adaptation of practices. We also identify technical, cultural, and political elements of fit (or misfit) between diffusing practices and adopters and analyze how the process of attaining fit across these elements can trigger different patterns of adaptation.
The Mario Einaudi Center for International Studies Working Paper Series Does Corruption Produce Unsafe Drivers ?

We follow 822 applicants through the process of obtaining a driver’s license in New Delhi, India. To understand how the bureaucracy responds to individual and social needs, participants were randomly assigned to one of three groups: bonus, lesson, and comparison groups. Participants in the bonus group were offered a financial reward if they could obtain their license fast; participants in the lesson group were offered free driving lessons. To gauge driving skills, we performed a surprise driving test after participants had obtained their licenses. Several interesting facts regarding corruption emerge. First, the bureaucracy responds to individual needs. Those who want their license faster (e.g. the bonus group), get it 40% faster and at a 20% higher rate. Second, the bureaucracy is insensitive to social needs. The bonus group does not learn to drive safely in order to obtain their license: in fact, 69% of them were rated as “failures” on the independent driving test. Those in the lesson group, despite superior driving skills, are only slightly more likely to obtain a license than the comparison group and far less likely (by 29 percentage points) than the bonus group. Detailed surveys allow us to document the mechanisms of corruption. We find that bureaucrats arbitrarily fail drivers at a high rate during the driving exam, irrespective of their ability to drive. To overcome this, individuals pay informal “agents” to bribe the bureaucrat and avoid taking the exam altogether. An audit study of agents further highlights the insensitivity of agents’ pricing to driving skills. Together, these results suggest that bureaucrats raise red tape to extract bribes and that this corruption undermines the very purpose of regulation.
How Health Professionals Rate Painfulness of Childhood Injuries and Illnesses: A Survey Study

ABSTRACT Pediatric pain management has become well established in developed countries but may lag behind in developing countries, where potentially painful diseases such as gastroenteritis and meningitis are even more common. This survey asked health care givers in the developed and developing worlds to rate pain intensity of 12 common childhood diseases and to inventory the pharmacological and nonpharmacological treatment modalities in their settings. A survey was distributed online (Surveygizmo 3.0) to pediatric health caregivers who rated perceived painfulness of 12 diseases on a 0 to 10 numerical rating scale or stated that the disease was primarily discomforting in their opinion. Also they inventoried the pharmacological and nonpharmacological interventions they utilize in their setting. Sixty-five respondents completed the survey, of whom almost three thirds (72.3%) came from developed countries. Median painfulness scores ranged from 5 (chickenpox) to 9 (compound tibial fracture). The respondents considered a number of diseases that are more often seen in developing countries as painful. Pediatric pain management in the developing world should be improved in view of the high incidences of potentially painful diseases and the lack of (non)pharmacological interventions.
Spatio-temporal Validation of Multimedia Documents

A multimedia document authoring system should provide analysis and validation tools that help authors find and correct mistakes before document deployment. Although very useful, multimedia validation tools are not often provided. Spatial validation of multimedia documents may be performed over the initial position of media items before presentation starts. However, such an approach does not lead to ideal results when media item placement changes over time. Some document authoring languages allow the definition of spatio-temporal relationships among media items and they can be moved or resized during runtime. Current validation approaches do not verify dynamic spatio-temporal relationships. This paper presents a novel approach for spatio-temporal validation of multimedia documents. We model the document state, extending the Simple Hypermedia Model (SHM), comprising media item positioning during the whole document presentation. Mapping between document states represent time lapse or user interaction. We also define a set of atomic formulas upon which the author's expectations related to the spatio-temporal layout can be described and analyzed.
The Un/Acceptability of Virtual Moral Practices: An Empirical and Ethical Inquiry

This article conjoins a foundation in moral philosophy with an empirical study on the un/acceptability of moral practices in 'Second Life' SL. SL-residents were asked to rank morally charged SL-scenarios in a classification from 'most unacceptable' to 'most acceptable' and, while doing so, to reason out loud about their ranking. The analysis presented here focuses on their converging and diverging arguments. Regarding converging arguments, there was consensus on the unacceptability of six scenarios. Research participants believed these scenarios transcend the merely virtual and they subsequently grounded their argumentation in actual principles. They further agreed upon seven scenarios as acceptable; these scenarios were considered as typical features of SL and subsequently were not morally problematized. Regarding other scenarios, no consensus was reached. The author discusses these findings in terms of their ethical implications and in light of current approaches in the field of 'computer ethics'.
Cerebral dural arteriovenous fistulas and aneurysms.

OBJECT The association of aneurysms and cerebral arteriovenous malformations is well established in the literature. Aside from a small number of case reports and small patient series, this association has not been well explored with cerebral dural arteriovenous fistulas (DAVFs). This study was designed to elucidate this relationship in the authors' own patient cohort with DAVFs. METHODS Cerebral angiograms of 56 patients with 70 DAVFs were reviewed for the presence of cerebral aneurysms. Background patient demographics, mode of presentation, and DAVF and aneurysm angiographic characteristics were noted. RESULTS Twelve patients (21%) had aneurysms in addition to their DAVF. Three patients had multiple aneurysms. Of a total of 15 aneurysms, 5 (33%) occurred on DAVF feeding arteries and 10 (67%) were in remote locations. These patients more commonly presented with hemorrhage (58% vs 20% for those without aneurysms). Aneurysms were associated with DAVFs in any location (feeding artery or remote), but flow-related feeding artery aneurysms were more likely to be associated with Borden Type III DAVFs. CONCLUSIONS Twenty-one percent of patients with cerebral DAVFs also had aneurysms in this patient cohort. It is thus prudent to perform 6-vessel digital subtraction angiography on patients with DAVFs to rule out potential feeding artery and remote aneurysms. This association may be explained by flow-related phenomena, the initial inciting event leading to DAVF formation, as well as a potential genetic component or predisposition to develop these lesions.
Transthyretin (ATTR) amyloidosis nephropathy: lessons from a TTR stabilizer molecule

Unidade Corino de Andrade, Porto, Portugal, Unit for Multidisciplinary Research in Biomedicine (UMIB), Instituto de Ciências Biomédicas Abel Salazar (ICBAS), Porto University, Porto, Portugal, Department of Neurology, Centro Hospitalar do Porto, Porto, Portugal, Department of Neurophisiology, Centro Hospitalar do Porto, Porto, Portugal, Department of Nephrology, Centro Hospitalar do Porto, Porto, Portugal, and School of Economics and LIAAD-INESC Porto LA, Porto University, Porto, Portugal
Demo Abstract: A LoRa Wireless Mesh Networking Module for Campus-Scale Monitoring

LoRa, an emerging wireless technology, is examined for long range communication performance in a large area. Although LoRa shows good performance for long-distance transmission in the countryside, its radio signals can be attenuated and interfered with by buildings, trees and other signal sources. In urban areas, our observation shows that LoRa requires a dense deployment of LoRa gateways to ensure that indoor LoRa devices can transfer data back to remote servers. Mesh networking is a solution for increasing the communication range and packet delivery ratio without the need to install additional LoRa gateways. This study presents our design of a LoRa mesh-networking module for IoT applications (e.g.,collecting data from multiple, widely distributed sensors on a university campus). We deployed 19 LoRa mesh-networking devices distributed in an 800m by 600m area on campus to serve as a gateway and to collect data at one-minute intervals. The results show our LoRa mesh networking module achieved a 88.49% packet delivery ratio (PDR), while the LoRaWAN in star-network topology was only 58.7% under the same conditions.