Miracle-dz/UniFAR-FTUs huggingface dataset:
The Development and Organization of Therapeutic Radiology in Sweden1

Sweden has at present a population of 7.5 million. Just under 2 million live in the sparsely populated northern two-thirds of the country. The other 5.5 million occupy the industrialized third in the south. There are five medical faculties: in Stockholm, Uppsala, Lund, Gothenburg, and Umea. The Last Decade of the Nineteenth Century The question as to who should receive the honor of being the first to have achieved a cure in cancer has been contended, but there seems to be justification for saying that it should go to two Swedes, Tor Stenbeck and Tage SjO gren, both of them general practitioners in Stockholm. On July 4, 1899, Stenbeck began to use roentgen therapy in a woman of forty-nine with basal-cell cancer on the nose. After a total of ninety-nine treatments over a period of several months, the patient was permanently cured. She was presented before a meeting of the Swedish Society of Medicine on Dec. 19 of the same year and was also shown to the members at the Second International Congress of Radiolo.
Non-viral delivery of nuclear factor-κB decoy ameliorates murine inflammatory bowel disease and restores tissue homeostasis

Background: Nuclear factor-κB (NF-κB) is a key transcriptional regulator of inflammatory bowel disease (IBD). Aim: To investigate the therapeutic potential of a locally administered “non-viral” nuclear factor-κB decoy (NFκBD) in multiple experimental models of IBD. Methods: A fully phosphorothioated decoy oligonucleotide with improved stability that specifically binds NF-κB and blocks inflammatory mediators regulated by this transcription factor without the help of viral envelope-assisted delivery was developed. The therapeutic effects of NFκBD were studied in the trinitrobenzene sulphonic acid, oxazolone and dextran sodium sulphate induced colitis models. Results: Intracolonic administration of NFκBD results in the delivery of NFκBD to inflammatory cells and a reduction of NF-κB heterodimers. In the T helper cell 1-driven trinitrobenzene sulphonic acid-induced colitis model, mice receiving NFκBD treatment exhibit a dose-dependent reduction in disease severity and a more rapid recovery to normal body weight, similar to a clinically relevant dose of budesonide. Clinical efficacy was corroborated by considerable reductions in colitis pathology and tissue levels of several pro-inflammatory markers, including tumour necrosis factor α, interleukin 6, interleukin 1β and monocyte chemotactic protein 1. NFκBD also mitigates disease activity in the T helper cell 2-like oxazolone colitis and epithelial injury-related acute dextran sodium sulphate colitis models. Interestingly, restoration of tissue homeostasis is observed in NFκBD-treated animals with the rapid re-emergence of functional goblet cells and a return to normal patterns of cell proliferation in the mucosal epithelium and smooth muscle cell layers. Conclusions: These data support the potential use of “naked” NFκBD as a cross-functional therapeutic in IBD, and show for the first time that it can facilitate the restoration of colon homeostasis and function.
Species selection considerations for preclinical toxicology studies for biotherapeutics

Background: Preclinical efficacy and safety studies, especially chronic studies, can be difficult to perform when the candidate therapeutic agent is a human protein due to the specificity of these molecules for the human target. The main issues are: i) the human protein or target may not be pharmacologically active in rodents or dogs, the standard toxicology species; or ii) the therapeutic agent may be so immunogenic in these species, that longer duration studies are not possible due to the formation of neutralizing antibodies. Thus, preclinical safety testing of biotherapeutics poses a particular challenge in selecting a relevant animal species for use in toxicology studies. Objective: This article will discuss the considerations that are unique to safety assessment of biotherapeutics and will provide alternatives to the standard toxicity testing which is conducted for small molecules. Methods: This article is based on published information with regards to species selection considerations as well as information from the FDA website on several marketed compounds. In addition, discussions of this topic that have occurred in public forums as well as the experience of the author are considered. Conclusion: The most important consideration in species selection for a biotherapeutic is that the drug is pharmacologically active in the preclinical species. This is a key consideration as biotherapeutics are highly targeted and rarely, if ever, demonstrate off-target toxicity. Because of this species specificity, nonhuman primates are often the only relevant species that can be used to assess the safety of a biotherapeutic. Other alternatives such as use of a homologous protein in rodents or the use of transgenic or knockout mice can also be used to assess safety although the caveats to these approaches must be considered.
Geometrically consistent plane extraction for dense indoor 3D maps segmentation

Modern SLAM systems with a depth sensor are able to reliably reconstruct dense 3D geometric maps of indoor scenes. Representing these maps in terms of meaningful entities is a step towards building semantic maps for autonomous robots. One approach is to segment the 3D maps into semantic objects using Conditional Random Fields (CRF), which requires large 3D ground truth datasets to train the classification model. Additionally, the CRF inference is often computationally expensive. In this paper, we present an unsupervised geometric-based approach for the segmentation of 3D point clouds into objects and meaningful scene structures. We approximate an input point cloud by an adjacency graph over surface patches, whose edges are then classified as being either on or off. We devise an effective classifier which utilises both global planar surfaces and local surface convexities for edge classification. More importantly, we propose a novel global plane extraction algorithm for robustly discovering the underlying planes in the scene. Our algorithm is able to enforce the extracted planes to be mutually orthogonal or parallel which conforms usually with human-made indoor environments. We reconstruct 654 3D indoor scenes from NYUv2 sequences to validate the efficiency and effectiveness of our segmentation method.
The Outcome of Haematological Malignancy in Scottish Intensive Care Units

To study the prognostic indicators and outcome in patients with haematological malignancy requiring intensive care, we identified 714 adult patients and analysed their clinical audit data. Mean APACHE II score was 24. Main admitting diagnoses were acute lymphoma (43%) and acute leukaemia (28%). There was a high requirement for acute organ support. Intensive care unit (ICU) mortality was 39% and hospital mortality 55%, with a standardised mortality rate of 1.05 (0.98–1.13). Factors predictive of outcome after multivariate analysis were: cardiopulmonary resuscitation (CPR) in the 24-hours before ICU admission, inotropic support in the first 24-hours, APACHE II score and requirement for ventilatory support immediately prior to, or at admission to the ICU. Neutropaenia was not an independent predictor. Patients with neutropaenic septic shock and multiorgan failure left hospital. Hospital mortality for this group is comparable to that of non-cancer patients admitted with multi-organ system failure. The reluctance to admit such patients to ICU may be unjustified.
Object identification from few examples by improving the invariance of a Deep Convolutional Neural Network

The development of reliable and robust visual recognition systems is a main challenge towards the deployment of autonomous robotic agents in unconstrained environments. Learning to recognize objects requires image representations that are discriminative to relevant information while being invariant to nuisances, such as scaling, rotations, light and background changes, and so forth. Deep Convolutional Neural Networks can learn such representations from large web-collected image datasets and a natural question is how these systems can be best adapted to the robotics context where little supervision is often available. In this work, we investigate different training strategies for deep architectures on a new dataset collected in a real-world robotic setting. In particular we show how deep networks can be tuned to improve invariance and discriminability properties and perform object identification tasks with minimal supervision.
Magnetic resonance colonography without bowel cleansing: a prospective cross sectional study in a screening population

Background and aim: To evaluate the diagnostic accuracy of magnetic resonance colonography (MRC) without bowel cleansing in a screening population and compare the results to colonoscopy as a standard of reference. Methods: 315 screening patients, older than 50 years with a normal risk profile for colorectal cancer, were included in this study. For MRC, a tagging agent (5.0% Gastrografin, 1.0% barium sulphate, 0.2% locust bean gum) was ingested with each main meal within 2 days prior to MRC. No bowel cleansing was applied. For the magnetic resonance examination, a rectal water enema was administered. Data collection was based on contrast enhanced T1 weighted images and TrueFISP images. Magnetic resonance data were analysed for image quality and the presence of colorectal lesions. Conventional colonoscopy and histopathological samples served as reference. Results: In 4% of all colonic segments, magnetic resonance image quality was insufficient because of untagged faecal material. Adenomatous polyps >5 mm were detected by means of MRC, with a sensitivity of 83.0%. Overall specificity was 90.2% (false positive findings in 19 patients). However, only 16 of 153 lesions <5 mm and 9 of 127 hyperplastic polyps could be visualised on magnetic resonance images. Conclusions: Faecal tagging MRC is applicable for screening purposes. It provides good accuracy for the detection of relevant (ie, adenomatous) colorectal lesions >5 mm in a screening population. However, refinements to optimise image quality of faecal tagging are needed.
RNA-sequencing analysis of core binding factor AML identifies recurrent ZBTB7A mutations and defines RUNX1-CBFA2T3 fusion signature.

To the editor: RUNX1 (also known as AML1 or CBFA2 ) and CBFB encode the α and β subunits of a heterodimeric core binding transcription factor complex involved in the development of normal hematopoiesis (reviewed by de Bruijn and Speck[1][1]). Both genes are rearranged in acute myeloid leukemia (
Enhancing Drug Court Success

This study evaluates the impact of enhanced drug court services in a large county in Southern California. These enhanced services, including specialty counseling groups, educational/employment resources, and increased Residential Treatment (RT) beds, were designed to increase program retention and successful completion (graduation) of drug court. This study examines outcomes for 477 male and 273 female drug court participants between January 2004 and March 2005 in Orange County, California. Data were gathered from various sources including the Drug Court management information system (MIS) and probation records. The results suggest that several enhancements individually increase participation retention (as opposed to termination) in drug court, particularly education, employment, RT, and two specialty counseling groups (Alcohol Recovery and Mask of Addiction). Similarly, participant graduation rates were improved with the individual effects of education, employment, and the same two specialty counseling groups. The combination of RT, specialty counseling groups, and employment achievement increased graduation rates for drug court participants. This research suggests further examination of these variables in alternate settings to determine the extent to which these strong but preliminary results are generalizable.
Guidelines on the management of common bile duct stones (CBDS)

The last 30 years have seen major developments in the management of gallstone-related disease, which in the United States alone costs over 6 billion dollars per annum to treat. Endoscopic retrograde cholangiopancreatography (ERCP) has become a widely available and routine procedure, whilst open cholecystectomy has largely been replaced by a laparoscopic approach, which may or may not include laparoscopic exploration of the common bile duct (LCBDE). In addition, new imaging techniques such as magnetic resonance cholangiography (MR) and endoscopic ultrasound (EUS) offer the opportunity to accurately visualise the biliary system without instrumentation of the ducts. As a consequence clinicians are now faced with a number of potentially valid options for managing patients with suspected CBDS. It is with this in mind that the following guidelines have been written.
Immunology of the gut and liver: a love/hate relationship

The gut digests, absorbs and metabolises nutrients whilst also acting as a barrier to pathogens entering from the intestinal lumen. Not all intestinal microbes are harmful and the full development of the gut immune system is shaped by interactions with commensal bacteria in a complex interplay which allows responses to harmless bacteria and nutrients to be suppressed whilst developing protective immune response against pathogens(1;2). Most of these responses occur in the intestinal mucosa and underlying lamina propria however transport of nutrients or translocation of pathogens into the portal circulation means that a second level of protection is required in the liver to respond to antigens that evade the gut immune system(3). In addition pathogens can enter the liver directly via the systemic circulation or from the gut lumen via the biliary epithelium. Immune responses in the gut and to a lesser extent liver are well-described but the mechanisms that control immunological cross-talk between these two linked sites are only beginning to be elucidated(4). They provide insights into the pathogenesis of diseases that affect both sites including infections and inflammatory bowel disease (IBD).
DNA barcoding and the taxonomy of Microgastrinae wasps (Hymenoptera, Braconidae): impacts after 8 years and nearly 20 000 sequences

Microgastrine wasps are among the most species‐rich and numerous parasitoids of caterpillars (Lepidoptera). They are often host‐specific and thus are extensively used in biological control efforts and figure prominently in trophic webs. However, their extraordinary diversity coupled with the occurrence of many cryptic species produces a significant taxonomic impediment. We present and release the results of 8 years (2004–2011) of DNA barcoding microgastrine wasps. Currently they are the best represented group of parasitoid Hymenoptera in the Barcode of Life Data System (BOLD), a massive barcode storage and analysis data management site for the International Barcoding of Life (iBOL) program. There are records from more than 20 000 specimens from 75 countries, including 50 genera (90% of the known total) and more than 1700 species (as indicated by Barcode Index Numbers and 2% MOTU). We briefly discuss the importance of this DNA data set and its collateral information for future research in: (1) discovery of cryptic species and description of new taxa; (2) estimating species numbers in biodiversity inventories; (3) clarification of generic boundaries; (4) biological control programmes; (5) molecular studies of host‐parasitoid biology and ecology; (6) evaluation of shifts in species distribution and phenology; and (7) fostering collaboration at national, regional and world levels. The integration of DNA barcoding with traditional morphology‐based taxonomy, host records, and other data has substantially improved the accuracy of microgastrine wasp identifications and will significantly accelerate further studies on this group of parasitoids.
THE PULSE AFTER A MARATHON RACE

The question of the possibility of producing alternation of the pulse by very vigorous and prolonged exertion was the incentive to a study of the pulse of twenty men who ran the annual Boston Marathon of 25 miles from Ashland to Boston, April 19, 1916. Myocardial exhaustion resulting from damage such as that produced by arteriosclerosis or syphilis has been shown to be an important cause of alternation of the pulse. The greater the strain on such a heart, the more marked is likely to be the alternation. The strain necessary to sustain a high blood pressure is especially likely to bring out alternation. Extreme and prolonged tachycardia, as in auricular flutter or paroxysmal tachycardia, may result in pulsus alternans. But it has never been shown, so far as I am aware, that alternation has been found in the pulse of a normal individual after severe exertion. Von Tabora 1
Genetic assessment of safflower (Carthamus tinctorius L.) collection with microsatellite markers acquired via pyrosequencing method

A genetic evaluation of safflower germplasm collections derived from different geographical regions and countries will provide useful information for sustainable conservation and the utilization of genetic diversity. However, the molecular marker information is limited for evaluation of genetic diversity of safflower germplasm. In this study, we acquired 509 putative genomic SSR markers for sufficient genome coverage using next‐generation sequencing methods and characterized thirty polymorphic SSRs in safflower collection composed of 100 diverse accessions. The average allele number and expected heterozygosity were 2.8 and 0.386, respectively. Analysis of population structure and phylogeny based on thirty SSR profiles revealed genetic admixture between geographical regions contrary to genetic clustering. However, the accessions from Korea were genetically conserved in distinctive groups in contrast to other safflower gene pool. In conclusion, these new genomic SSRs will facilitate valuable studies to clarify genetic relationships as well as conduct population structure analyses, genetic map construction and association analysis for safflower.
HeFPipe: a complete analytical pipeline for heterozygosity‐fitness correlation studies

As the body of heterozygosity‐fitness correlation (HFC) research grows, more and increasingly complicated tests have become an integral part of a typical HFC analysis (Chapman et al. 2009). Currently, no software is available to undertake conversion between the file formats required to conduct all of these tests and to conduct the main regression analyses at the core of all HFCs. Heterozygosity‐Fitness Pipeline (HeFPipe) is a script written in Python that accomplishes both of these tasks for studies based on microsatellite data. HeFPipe is designed to be used from the command line terminal and will run on any Mac OSX computer. The script takes input in the form of allele reports from either the genotype‐calling software, GeneMapper or GeneMarker, and reconfigures the data into GENEPOP (Raymond & Rousset 1995), Rhh (Alho et al. 2010), RMES (David et al. 2007) and GEPHAST (Amos & Acevedo‐Whitehouse 2009) formats. The script is also equipped to reformat the output from GENEPOP on the Web (option 5) and Rhh into csv spreadsheets that can be incorporated into downstream analyses. HeFPipe accommodates user‐provided lists of samples and markers to be included in or excluded from analyses. HeFPipe is equipped to create generalized linear models (GLMs) from both the main data set and subsets of the data. Finally, HeFPipe allows users to explore single‐marker effects and conduct correlation analyses. The script, a comprehensive manual, a link to a series of video tutorials, and an example data set are available from GitHub (http://github.com/Atticus29/HeFPipe_rpos).
NOD2-expressing bone marrow-derived cells appear to regulate epithelial innate immunity of the transplanted human small intestine

Background: Intestinal allograft rejection resembles Crohn’s disease clinically and pathologically. An understanding of its mechanism could impact this life-saving procedure, as well as provide insight into the pathophysiology of inflammatory bowel disease. The NOD2 protein has been implicated as a key player in intestinal immune health, as a consequence of the discovery of three polymorphisms linked with Crohn’s disease. An investigation was carried out to determine whether epithelial immune function and graft survival were influenced by NOD2 mutations in an intestinal transplant population. Methods: The NOD2 genotypes of 34 transplants performed consecutively over the past 3 years were determined. The NOD2 genotypes were related to clinical outcomes and the expression of certain intestinal antimicrobial peptides (AMPs) believed to protect the epithelium. Results: An unexpectedly high percentage of recipients, 35%, possessed NOD2 polymorphisms, while 8.6% of donors had comparable mutations. The likelihood of allograft failure was about 100-fold higher in recipients with mutant NOD2 alleles compared with recipients with wild-type NOD2 loci. Rejection in NOD2 mutant recipients was characterised by decreased expression of certain Paneth cell and enterocyte AMPs, prior to the onset of epithelial injury and inflammation. Conclusions: Crohn’s disease-associated polymorphisms in the NOD2 gene in the recipient represent a critical immunological risk factor for intestinal allograft rejection. Compromised epithelial defences precede visible epithelial injury and inflammatory infiltration. The association of impaired epithelial immunity with the recipient’s genotype suggests that certain NOD2-expressing cells of haematopoietic origin play a role in the process, perhaps by regulating expression of certain epithelial AMPs within the allograft.
Characterizing DNA preservation in degraded specimens of Amara alpina (Carabidae: Coleoptera)

DNA preserved in degraded beetle (Coleoptera) specimens, including those derived from dry‐stored museum and ancient permafrost‐preserved environments, could provide a valuable resource for researchers interested in species and population histories over timescales from decades to millenia. However, the potential of these samples as genetic resources is currently unassessed. Here, using Sanger and Illumina shotgun sequence data, we explored DNA preservation in specimens of the ground beetle Amara alpina, from both museum and ancient environments. Nearly all museum specimens had amplifiable DNA, with the maximum amplifiable fragment length decreasing with age. Amplification of DNA was only possible in 45% of ancient specimens. Preserved mitochondrial DNA fragments were significantly longer than those of nuclear DNA in both museum and ancient specimens. Metagenomic characterization of extracted DNA demonstrated that parasite‐derived sequences, including Wolbachia and Spiroplasma, are recoverable from museum beetle specimens. Ancient DNA extracts contained beetle DNA in amounts comparable to museum specimens. Overall, our data demonstrate that there is great potential for both museum and ancient specimens of beetles in future genetic studies, and we see no reason why this would not be the case for other orders of insect.