Miracle-dz/UniFAR-FTUs huggingface dataset:
Dubowitz Syndrome Is a Complex Comprised of Multiple, Genetically Distinct and Phenotypically Overlapping Disorders

Dubowitz syndrome is a rare disorder characterized by multiple congenital anomalies, cognitive delay, growth failure, an immune defect, and an increased risk of blood dyscrasia and malignancy. There is considerable phenotypic variability, suggesting genetic heterogeneity. We clinically characterized and performed exome sequencing and high-density array SNP genotyping on three individuals with Dubowitz syndrome, including a pair of previously-described siblings (Patients 1 and 2, brother and sister) and an unpublished patient (Patient 3). Given the siblings' history of bone marrow abnormalities, we also evaluated telomere length and performed radiosensitivity assays. In the siblings, exome sequencing identified compound heterozygosity for a known rare nonsense substitution in the nuclear ligase gene LIG4 (rs104894419, NM_002312.3:c.2440C>T) that predicts p.Arg814X (MAF:0.0002) and an NM_002312. 3:c.613delT variant that predicts a p.Ser205Leufs*29 frameshift. The frameshift mutation has not been reported in 1000 Genomes, ESP, or ClinSeq. These LIG4 mutations were previously reported in the sibling sister; her brother had not been previously tested. Western blotting showed an absence of a ligase IV band in both siblings. In the third patient, array SNP genotyping revealed a de novo ∼3.89 Mb interstitial deletion at chromosome 17q24.2 (chr 17:62,068,463–65,963,102, hg18), which spanned the known Carney complex gene PRKAR1A. In all three patients, a median lymphocyte telomere length of ≤1st centile was observed and radiosensitivity assays showed increased sensitivity to ionizing radiation. Our work suggests that, in addition to dyskeratosis congenita, LIG4 and 17q24.2 syndromes also feature shortened telomeres; to confirm this, telomere length testing should be considered in both disorders. Taken together, our work and other reports on Dubowitz syndrome, as currently recognized, suggest that it is not a unitary entity but instead a collection of phenotypically similar disorders. As a clinical entity, Dubowitz syndrome will need continual re-evaluation and re-definition as its constituent phenotypes are determined.
Nonlinear circuits for naturalistic visual motion estimation

Many animals use visual signals to estimate motion. Canonical models suppose that animals estimate motion by cross-correlating pairs of spatiotemporally separated visual signals, but recent experiments indicate that humans and flies perceive motion from higher-order correlations that signify motion in natural environments. Here we show how biologically plausible processing motifs in neural circuits could be tuned to extract this information. We emphasize how known aspects of Drosophila's visual circuitry could embody this tuning and predict fly behavior. We find that segregating motion signals into ON/OFF channels can enhance estimation accuracy by accounting for natural light/dark asymmetries. Furthermore, a diversity of inputs to motion detecting neurons can provide access to more complex higher-order correlations. Collectively, these results illustrate how non-canonical computations improve motion estimation with naturalistic inputs. This argues that the complexity of the fly's motion computations, implemented in its elaborate circuits, represents a valuable feature of its visual motion estimator. DOI: http://dx.doi. org/10.7554/eLife.09123. 001
Smoking characteristics and cessation in patients with thromboangiitis obliterans.

AIM Describe the smoking characteristics and the results of a smoking intervention programme involving 27 cigarette smokers with Thromboangiitis Obliterans (TAO). METHODS Clinical records of all cigarette smokers with TAO that attended our smoking treatment clinic from 1990 to 2004 were reviewed. Demographic and smoking characteristics, the type of smoking treatment received and its efficacy and safety up to 12 months was abstracted. Treatment consisted of the combination of behavioural and pharmacological treatment. The behavioural treatment was delivered in eight individual visits: one baseline visit and seven follow-up visits. Pharmacological treatment consisted of combinations of nicotine patches and nicotine gum (NRT) and/or bupropion. This is an 'intent to treat' analysis. A descriptive analysis of the variables was performed. Qualitative variable relationships were tested using the chi-square test for independence, or Fisher's Exact Test when expected values were less than five. Statistical significance was accepted at a level of p < 0.05. RESULTS 27 cigarette smokers (23 male and 4 female), mean (SD) age 36.07 (7.23), mean FTND-score 8.4 (1.4), smoked a mean of 29.6 (7.71) cigarettes daily. They attended our clinic a mean of 45.48 (8.63) months after onset of TAO. Their mean number of attempts to stop was 3.22 (2.75). The continuous abstinence rate decreased from 29% at the end of treatment to 18.5% at 12-month follow up. The seven day point prevalence abstinence rate at the 12th month of follow up was 40.7%. We found that continuous abstinence at 6 and 12 months was more frequent among those with multiple previous stop attempts (p = 0.003 and p = 0.001, respectively). There were no significant differences in abstinence outcomes between groups. Incidence of adverse effects was similar to other smokers seeking treatment. All the smokers who achieved continuous tobacco abstinence had improvement in their disease and none of them underwent amputation, compared to 50% of those who resumed smoking and later required an amputation. CONCLUSIONS Continuous abstinence rates among treated cigarette smokers with TAO are relatively low, but abstinence does improve symptoms and reduce the likelihood of amputation. More aggressive treatment programmes need to be developed for this high risk, highly tobacco dependent population.
A Data-Driven Shape Model for Human Body Reconstruction from Photos

In this paper, we present a data-driven approach to the problem of reconstructing human body models from 2D images. One of the key tasks in reconstructing the 3D model from image data is shape recovery, a task done until now in utterly geometric way, in the domain of human body modeling. In contrast, we use data-driven deformable models that are obtained in a priori, where a collection of range scans of real human body is structured and statically processed. We use a sparse set of feature points and silhouette data both on the input images and on the template model to optimize the deformation parameters, such that the resulting model best matches the given silhouette. In the presence of ambiguity either from the noise or missing views, our technique has a bias towards representing as much as possible the previously acquired shape. We then generate texture coordinates by projecting the modified template model onto the front and back images. Our technique has shown to reconstruct successfully human body models from minimum number of orthogonal images.
c‐myc and c‐fos expression in differentiating mouse primary keratinocytes.

Expression of the myc and fos genes has been monitored in mouse primary keratinocytes after induction of terminal differentiation by calcium or tetradecanoylphorbol acetate (TPA). myc RNA levels in growing cells are very high and remain elevated even at late times after calcium‐induced differentiation. Thus, keratinocytes provide the first example of normal primary cells with persistent c‐myc expression irrespective of their proliferative or differentiated state. fos expression is also relatively unaffected by addition of calcium. In contrast to calcium, TPA‐induced differentiation is accompanied by dramatic changes in proto‐oncogene expression: marked c‐fos induction and considerable although transient decrease in c‐myc expression. These effects might be important for the keratinocyte response to TPA: TPA treatment of a keratinocyte cell line (RBK) resistant to this substance has no effect on c‐myc expression and leads only to minimal c‐fos induction. In these cells full fos induction can still be triggered by addition of fresh medium. Thus, the fos gene in normal keratinocytes is inducible through at least two independent mechanisms, only one of which has been lost during derivation of the TPA‐resistant cell line.
Incidence and factors influencing the development of fistula-in-ano after incision and drainage of perianal abscesses.

OBJECTIVE The aims of the present study were to evaluate the incidence offistula-in-ano following incision and drainage of acute perianal abscess and to determine factors influencing the fistula formation. MATERIAL AND METHOD Patients with a first-time perianal abscess or intersphincteric abscess who underwent incision and drainage at Siriraj Hospital from January 2005 to June 2008 were reviewed Patients with coexisting fistula or perianal Crohn's disease were excluded. Incidence and risk factors for fistula formation were analyzed. RESULTS Sixty-four patients were reviewed (50 males, 14 females). The average age of the patients was 44 years (range 19-82). The average follow-up period was 30 months (range 10-53). Twenty patients (31%) developed fistula-in-ano following incision and drainage. Gender; smoking, alcohol consumption, fever; leukocytosis, and location of abscess were not predictive of fistula formation. Univariate analysis showed that patients aged under 40 years and non-diabetic patients tended to have a higher risk for developing the fistula (43% vs. 21%, OR 2.95, 95% CI 0.98-8.85; p = 0.05 and 38% vs. 13%, OR 4.2, 95% CI 0.85-20.83; p = 0.071, respectively). However, patients receiving perioperative antibiotics (ATB) were less likely to develop subsequent fistula in both univariate and multivariate analysis. The FIA rate in non-ATB group was 48% and only 17% in ATB group (OR 4.5, 95% CI 1.44-14.13; p = 0.01). CONCLUSION The incidence of fistula-in-ano following incision and drainage of perianal abscess was 31%. Patients aged under 40 years and non-diabetic patients appeared to have a higher risk for fistula formation. Administration of perioperative antibiotics significantly reduced the rate of subsequent fistula formation.
Tracing evolutionary pressure

MOTIVATION Recent advances in sequencing techniques have yielded enormous amounts of protein sequence data from various species. This large dataset allows sequence comparison between paralogous and orthologous proteins to identify motifs or functional positions that account for the differences of functional subgroups ('specificity' positions). Algorithms such as SDPpred and the two-entropies analysis (TEA) have been developed to detect such specificity positions from a multiple sequence alignment (MSA) grouped into classes according to certain biological functions. Other algorithms such as TreeDet compute a classification and then predict specificity positions associated with it. However, there are still many unresolved questions: Was the optimal subdivision of a protein family achieved? Do the definitions at different levels of the phylogenetic tree affect the prediction of specificity positions? Can the whole phylogenetic tree be used instead of only one level in it to predict specificity positions? RESULTS Here we present a novel method, TEA-O (Two-entropies analysis-Objective), to trace the evolutionary pressure from the root to the branches of the phylogenetic tree. At each level of the tree, a TEA plot is produced to capture the signal of the evolutionary pressure. A consensus TEA-O plot is composed from the whole series of plots to provide a condensed representation. Positions related to functions that evolved early (conserved) or later (specificity) are close to the lower-left or upper-left corner of the TEA-O plot, respectively. This novel approach allows an unbiased, user-independent, analysis of residue relevance in a protein family. We compared our TEA-O method with various algorithms using both synthetic and real protein sequences. The results show that our method is robust, sensitive to subtle differences in evolutionary pressure during evolution and comprehensive because all positions in the MSA are presented in the consensus plot. AVAILABILITY All computer programs and datasets used in this work are available at http://nava.liacs. nl/kye/TEA-O/ for academic use.
Algorithms for Visualizing Large Networks

Graphs are often used to encapsulate relationship between objects. Graph drawing enables visualization of such relationships. The usefulness of this visual representation is dependent on whether the drawing is aesthetic. While there are no strict criteria for aesthetics of a drawing, it is generally agreed, for example, that such a drawing has minimal edge crossing, with vertices evenly distributed in the space, connected vertices close to each other, and symmetry that may exist in the graph preserved. One of the earliest example of graph drawing is probably the Mill (also known as Morris) game boards, found in the 13th century The Book of Games, produced under the direction of Alfonso X (1221-1284), King of Castile (Spain). Other examples of early graph drawing are drawings of family trees, and trees of virtues and vices. In 1735, Euler presented and later published his famous paper [13] on the Seven Bridges of Konigsberg. The problem was to find a walk through the city of Konigsberg, which include two islands connected to the mainland by seven bridges (Figure 1). The walk must cross each bridge once and only once. Euler proved that such a walk is not possible. Euler’s paper laid the foundation of graph theory. Interestingly, however, Euler did not provide a drawing of the graph representation of the problem itself in the paper. In the 18th century, the Irish physicist, astronomer, and mathematician, William Hamilton, invented the Iconsian game. To play the game, one has to visit every node of a dodecahedral graph once, and back to the starting node. Every edge can be passed at most once. In 1857 he sold the game to a London game dealer for 25 Pounds (about 3000 US dollars in today’s money after taking inflation into account). The dealer made two versions; unfortunately, neither sold well, probably because the game was so simple that even a child could succeed. Around the same time, British mathematician Arthur Cayley wrote a paper on the enumeration of tree diagrams. In the paper he pioneered the
Paraproteins are a common cause of interferences with automated chemistry methods.

CONTEXT Previous studies have shown that paraproteins caused spurious results on individual analytes including total bilirubin (TBIL), direct bilirubin (DBIL), or HDL-cholesterol (HDL-C). Studies demonstrating paraprotein interferences with multiple analytes measured by different analyzers have not been reported. OBJECTIVE To systemically investigate interferences of paraproteins on TBIL, DBIL, and HDL-C measured by the Roche MODULAR and the Olympus AU2700. DESIGN Eighty-eight serum specimens with monoclonal gammopathies were analyzed using the Roche MODULAR and the Olympus AU2700. Paraprotein interferences with the MODULAR and AU2700 were identified by abnormal absorbance curves and confirmed by results from the Ortho Vitros 950 or inconsistent laboratory information. RESULTS Spurious results occurred in 89 of 528 measurements; 29 specimens did not demonstrate any interferences whereas 26 specimens gave spurious results in 2 to 4 of the 6 assays. Paraprotein interferences caused spuriously high levels of TBIL in 4 sera measured by the MODULAR. In contrast, paraprotein interferences on DBIL were observed by at least 1 method in 44% (39/88) of sera assayed, occurring almost exclusively with the AU2700. Paraprotein interferences with HDL-C results were present in 35% of specimens assayed with the MODULAR and 16% of specimens assayed with the AU2700. In specimens with interferences, spuriously low AU2700 DBIL, MODULAR HDL-C, and AU2700 HDL-C results occurred with 28%, 90%, and 91% of specimens, respectively. CONCLUSIONS We demonstrated that paraprotein interferences with TBIL, DBIL, and HDL-C are relatively common and provided explanations why these interferences occurred. Although it is difficult to predict which specimens cause interferences, spurious results appeared method and concentration dependent.
The Interplay of Host Microbiota and Parasitic Protozoans at Mucosal Interfaces: Implications for the Outcomes of Infections and Diseases

Infections by parasitic protozoans are largely neglected, despite threatening millions of people, particularly in developing countries. With descriptions of the microbiota in humans, a new frontier of investigation is developing to decipher the complexity of host–parasite–microbiota relationships, instead of the classic reductionist approach, which considers host–parasite in isolation. Here, we review with specific examples the potential roles that the resident microbiota can play at mucosal interfaces in the transmission of parasitic protozoans and in the progress of infection and disease. Although the mechanisms underlying these relationships remain poorly understood, some examples provide compelling evidence that specific components of the microbiota can potentially alter the outcomes of parasitic infections and diseases in humans. Most findings suggest a protective role of the microbiota, which might lead to exploratory research comprising microbiota-based interventions to prevent and treat protozoal infections in the future. However, these infections are often accompanied by an unbalanced microbiota and, in some specific cases, apparently, these bacteria may contribute synergistically to disease progression. Taken together, these findings provide a different perspective on the ecological nature of protozoal infections. This review focuses attention on the importance of considering polymicrobial associations, i.e., parasitic protozoans and the host microbiota, for understanding these human infections in their natural microbial context.
A capacity-building conceptual framework for public health nutrition practice

Abstract Objectives To describe a conceptual framework to assist in the application of capacity-building principles to public health nutrition practice. Design A review of the literature and consideration of the determinants of effective public health nutrition practice has been used to inform the development of a conceptual framework for capacity building in the context of public health nutrition practice. Result The limited literature supports a greater integration and application of capacity-building strategies and principles in public health nutrition practice, and that this application should be overt and strategic. A framework is proposed that identifies a number of determinants of capacity for effective public health nutrition action. The framework represents the key foundations for building capacity including leadership, resourcing and intelligence. Five key strategic domains supported by these foundation elements, including partnerships, organisational development, project management quality, workforce development and community development, are proposed. This framework can be used to assist the systematic assessment, development and evaluation of capacity-building activity within public health nutrition practice. Conclusions Capacity building is a strategy within public health nutrition practice that needs to be central to public health nutrition intervention management. The present paper defines, contextualises and outlines a framework for integrating and making explicit the importance of capacity building within public health nutrition practice at many levels.
The information age and the printing press: looking backward to see ahead

INTRODUCTION We are in the midst of the “Information Age. ” Pundits have proclaimed it for years; articles in the popular press have plumbed its implications for every imaginable enterprise;2 businesses are enamored with it; on-line and print magazines are devoted to it; government is wrestling with it, movies have been made about it; people are talking about it--can there be any doubt? So, where will it all lead and why should we care? And what exactly is the Information Age anyway? It is my intent in this paper to describe a way to think about what the Information Age is and where it will lead. And, put succinctly, we should all care because that way of thinking suggests the Information Age is likely to have profound effects throughout society--even if the specific effects are hard to see at this point. But I'm getting ahead of myself. At this point I want to suggest that it is both important and difficult to see where the information age might lead. Important, not least, because gargantuan fortunes are there to be made for those who see the future clearly. Important also, because information is affecting a wide variety of human enterprises in significant ways (businesses are "flattening" and globalizing; people are buying faxes, cell phones and computers; schools are wiring themselves in anticipation; governments are scrambling to handle information age problems, etc.). It is difficult to see where the information age is leading primarily because the technologies fueling it are still being developed and at a furious rate. It is difficult also because of the breadth of the impact of information technologies to date. With so many areas of society being affected, many effects are transitory, many are insignificant, some are contradictory and some are even undesirable. Because or perhaps in spite of both the importance and difficulty of addressing the future of the information age, there has been no shortage of attempts to do so. These attempts break down roughly into three categories. The first contains those who would project from the capabilities generated by information technology where
GB Virus C genotype determination in GB Virus‐C/HIV co‐infected individuals

Several recent studies have indicated that patients infected with human immunodeficiency virus (HIV) exhibit a beneficial effect of co‐infection with GB virus C (GBV‐C). The benefit is demonstrated by slower progression to acquired immunodeficiency syndrome (AIDS) and prolonged survival time after the development of AIDS. In some but not all studies, a significant association between GBV‐C/HIV co‐infection and increased CD4+ cell counts has been reported. To understand further the possible role that GBV‐C might play in the reduced morbidity and mortality among HIV‐infected patients, we sought to examine the presence of different GBV‐C genotypes in a cohort of co‐infected patients. PCR products derived from the 5′‐untranslated region (5′‐UTR) and the second envelope gene (E2) were sequenced directly and genotyped by phylogenetic analysis. While 5′‐UTR analysis delineated the major type, analysis of the complete E2 gene was required for identification of group 2 subtypes, designated 2a and 2b. Among 35 patients tested, GBV‐C genotype was determined for 33: two patients were infected with genotype 1, 12 with type 2a, and 19 with type 2b. Clinical data were available for 25 genotyped patients: one infected with genotype 1, nine with genotype 2a, and 15 with type 2b. CD4 cell counts tended to be lower in patients infected with genotype 2a compared with those with genotype 2b (310 ± 136 vs 430 ± 199, P = 0.054). Additional studies with larger cohorts from separate geographical regions are needed to determine whether a particular GBV‐C genotype is associated with reduced morbidity or mortality among HIV co‐infected patients. J. Med. Virol. 70:141–149, 2003. © 2003 Wiley‐Liss, Inc.