cometadata/datacite-titles-descriptions-related-identifiers huggingface dataset:
DOI: 10.6084/m9.figshare.5121283
title: Supplementary Material for: Alveolar Granulocytic Sarcoma of the Mandible in a Patient with HIV

description: <i>Background:</i> Granulocytic sarcoma (chloroma) occurs primarily in patients with acute myelogenous leukemia although it can also appear in connection with other myeloproliferative disorders. <i>Case Report:</i> We present the case of a 52-year-old human immunodeficiency virus (HIV)-positive female patient with a CD4+ count of 321 cells/ml, who developed an alveolar granulocytic sarcoma of the mandible. Pathological analysis of the tumor mass showed an infiltrate of immature cells which were positive for CD13, CD33, CD15, CD11b, and CD64, and negative for CD34, CD117, and HLA-DR. The patient achieved complete remission following a 1-week course of chemotherapy, however, 7 months later she developed a second granulocytic sarcoma in the left soleus muscle. The absolute CD4+ count had now reduced to 3 cells/ml with an inversion in the Th/Ts index (0.01), and she died of gram-negative sepsis 1 month later. Conclusions: Granulocytic sarcoma is extremely rare in patients with HIV. The case is discussed with reference to the literature.
DOI: 10.6084/m9.figshare.5121286
title: Supplementary Material for: Long-Range Comparison between Genes and Languages Based on Syntactic Distances

description: <i>Objective:</i> To propose a new approach for comparing genetic and linguistic diversity in populations belonging to distantly related groups. <i>Background:</i> Comparisons of linguistic and genetic differences have proved powerful tools to reconstruct human demographic history. Current models assume on both sides that similarities reflect either descent from common ancestry or the balance between isolation and contact. Most linguistic phylogenies are ultimately based on lexical evidence (roughly, words and morphemes with their sounds and meanings). However, measures of lexical divergence are reliable only for closely related languages, thus large-scale comparisons of genetic and linguistic diversity have appeared problematic so far. <i>Methods:</i> Syntax (abstract rules to combine words into sentences) appears more measurable, universally comparable, and stable than the lexicon, and hence certain syntactic similarities might reflect deeper linguistic relationships, such as those between distant language families. In this study, we for the first time compared genetic data to a matrix of syntactic differences among selected populations of three continents. <i>Results:</i> Comparing two databases of microsatellite (Short Tandem Repeat) markers and Single Nucleotides Polymorphisms (SNPs), with a linguistic matrix based on the values of 62 grammatical parameters, we show that there is indeed a correlation of syntactic and genetic distances. We also identified a few outliers and suggest a possible interpretation of the overall pattern. <i>Conclusions:</i> These results strongly support the possibility of better investigating population history by combining genetic data with linguistic information of a new type, provided by a theoretically more sophisticated method to assess the relationships between distantly related languages and language families.
DOI: 10.6084/m9.figshare.5121289
title: Supplementary Material for: M1 Protein-Dependent Intracellular Trafficking Promotes Persistence and Replication of <i>Streptococcus pyogenes</i> in Macrophages

description: <i>Streptococcus pyogenes</i> is an important human pathogen that causes a variety of diseases including life-threatening invasive diseases, such as toxic shock and deep tissue infections. Although <i>S. pyogenes</i> are classically considered extracellular pathogens, a clinical significance of an intracellular source has been emphasized. In patients with deep tissue infections, an intracellular reservoir of <i>S. pyogenes</i> within macrophages was shown to contribute to prolonged bacterial persistence. Here we demonstrate that intracellular survival of <i>S. pyogenes</i> in macrophages is associated with an M1 protein-dependent intracellular trafficking in the phagosomal-lysosomal pathway, which results in impaired fusion with lysosomes. The phagocytic vacuoles harbouring M1 protein-expressing bacteria not only served as a safe haven for the bacteria, but also as a replicating niche. An M1 protein-dependent modulation of macrophages was further supported by differences in NF-ĸB signalling between cells infected with either the wild-type or M1 protein-deficient strains, thereby indicating a suppressed inflammatory response when M1 protein was involved. Evidence of egress of bacteria out of their host cell and subsequent re-infection of new cells emphasize the importance of intracellular bacteria as a reservoir for dissemination of infection and continued tissue injury.
DOI: 10.6084/m9.figshare.5121292
title: Supplementary Material for: Parameters Governing Invasive Disease Propensity of Non-M1 Serotype Group A Streptococci

description: Group A <i>Streptococcus</i> (GAS) causes rare but life-threatening syndromes of necrotizing fasciitis and toxic shock-like syndrome in humans. The GAS serotype M1T1 clone has globally disseminated, and mutations in the control of virulence regulatory sensor kinase (<i>covRS)</i> operon correlate with severe invasive disease. Here, a cohort of non-M1 GAS was screened to determine whether mutation in <i>covRS</i> triggers systemic dissemination in divergent M serotypes. A GAS disease model defining parameters governing invasive propensity of differing M types is proposed. The vast majority of GAS infection is benign. Nonetheless, many divergent M types possess limited capacity to cause invasive infection. M1T1 GAS readily switch to a <i>covRS</i> mutant form that is neutrophil resistant and frequently associated with systemic infection. Whilst non-M1 GAS are shown in this study to less frequently accumulate <i>covRS</i> mutations in vivo, such mutants are isolated from invasive infections and exhibit neutrophil resistance and enhanced virulence. The reduced capacity of non-M1 GAS to switch to the hypervirulent <i>covRS</i> mutant form provides an explanation for the comparatively less frequent isolation of non-M1 serotypes from invasive human infections.
DOI: 10.6084/m9.figshare.5121280
title: Supplementary Material for: Rapid Neutrophil Destruction following Phagocytosis of Staphylococcus aureus

description: Mechanisms underlying the enhanced virulence phenotype of community-associated methicillin-resistant <i>Staphylococcus aureus</i> (CA-MRSA) are incompletely defined, but presumably include evasion of killing by human polymorphonuclear leukocytes (PMNs or neutrophils). To better understand this phenomenon, we investigated the basis of rapid PMN lysis after phagocytosis of USA300, a prominent CA-MRSA strain. Survival of USA300 clinical isolates after phagocytosis ultimately resulted in neutrophil lysis. PMNs containing ingested USA300 underwent morphological changes consistent with apoptosis, but lysed rapidly thereafter (within 6 h), whereas cells undergoing FAS-mediated apoptosis or phagocytosis-induced cell death remained intact. Phagosome membranes remained intact until the point of PMN destruction, suggesting lysis was not caused by escape of <i>S. aureus</i> from phagosomes or the cytolytic action of pore-forming toxins. Microarray analysis of the PMN transcriptome after phagocytosis of representative community-associated <i>S. aureus</i> and healthcare-associated MRSA strains revealed changes unique to community-associated <i>S. aureus</i> strains, such as upregulation of transcripts involved in regulation of calcium homeostasis. Collectively, the data suggest that neutrophil destruction after phagocytosis of USA300 is in part a form of programmed necrosis rather than direct lysis by <i>S. aureus</i> pore-forming toxins. We propose that the ability of CA-MRSA strains to induce programmed necrosis of neutrophils is a component of enhanced virulence.
DOI: 10.6084/m9.figshare.5121286.v1
title: Supplementary Material for: Long-Range Comparison between Genes and Languages Based on Syntactic Distances

description: <i>Objective:</i> To propose a new approach for comparing genetic and linguistic diversity in populations belonging to distantly related groups. <i>Background:</i> Comparisons of linguistic and genetic differences have proved powerful tools to reconstruct human demographic history. Current models assume on both sides that similarities reflect either descent from common ancestry or the balance between isolation and contact. Most linguistic phylogenies are ultimately based on lexical evidence (roughly, words and morphemes with their sounds and meanings). However, measures of lexical divergence are reliable only for closely related languages, thus large-scale comparisons of genetic and linguistic diversity have appeared problematic so far. <i>Methods:</i> Syntax (abstract rules to combine words into sentences) appears more measurable, universally comparable, and stable than the lexicon, and hence certain syntactic similarities might reflect deeper linguistic relationships, such as those between distant language families. In this study, we for the first time compared genetic data to a matrix of syntactic differences among selected populations of three continents. <i>Results:</i> Comparing two databases of microsatellite (Short Tandem Repeat) markers and Single Nucleotides Polymorphisms (SNPs), with a linguistic matrix based on the values of 62 grammatical parameters, we show that there is indeed a correlation of syntactic and genetic distances. We also identified a few outliers and suggest a possible interpretation of the overall pattern. <i>Conclusions:</i> These results strongly support the possibility of better investigating population history by combining genetic data with linguistic information of a new type, provided by a theoretically more sophisticated method to assess the relationships between distantly related languages and language families.
DOI: 10.6084/m9.figshare.5121295.v1
title: Supplementary Material for: Streptococcal Inhibitor of Complement Promotes Innate Immune Resistance Phenotypes of Invasive M1T1 Group A <i>Streptococcus</i>

description: Streptococcal inhibitor of complement (SIC) is a highly polymorphic extracellular protein and putative virulence factor secreted by M1 and M57 strains of group A <i>Streptococcus</i> (GAS). The <i>sic</i> gene is highly upregulated in invasive M1T1 GAS isolates following selection of mutations in the <i>covR/S</i> regulatory locus in vivo<i>.</i> Previous work has shown that SIC (allelic form 1.01) binds to and inactivates complement C5b67 and human cathelicidin LL-37. We examined the contribution of SIC to innate immune resistance phenotypes of GAS in the intact organism, using (1) targeted deletion of <i>sic</i> in wild-type and animal-passaged (<i>covS</i> mutant) M1T1 GAS harboring the <i>sic 1.84</i> allele and (2) heterologous expression of <i>sic</i> in M49 GAS, which does not possess the <i>sic</i> genein its genome. We find that M1T1 SIC production is strongly upregulated upon <i>covS</i> mutation but that the <i>sic</i> gene is not required for generation and selection of <i>covS</i> mutants in vivo. SIC 1.84 bound both human and murine cathelicidins and was necessary and sufficient to promote <i>covS</i> mutant M1T1 GAS resistance to LL-37, growth in human whole blood and virulence in a murine model of systemic infection. Finally, the <i>sic</i> knockout mutant M1T1 GAS strain was deficient in growth in human serum and intracellular macrophage survival. We conclude that SIC contributes to M1T1 GAS immune resistance and virulence phenotypes.
DOI: 10.6084/m9.figshare.5121277
title: Supplementary Material for: Horizontal Semicircular Canal Benign Paroxysmal Positional Vertigo: Effectiveness of Two Different Methods of Treatment

description: The aim of this study is to compare the results obtained using 2 methods of treatment for horizontal semicircular canal benign paroxysmal positional vertigo (HSC-BPPV): the barbecue maneuver + forced prolonged position (FPP) versus the Gufoni maneuver. In a randomized prospective clinical trial, we recruited 147 patients affected by HSC-BPPV. The primary outcome was the absence of vertigo and nystagmus upon application of the supine roll test during the follow-up examination. A statistical evaluation was performed in order to assess whether any parameters (e.g. age, duration of nystagmus and symptoms) could influence in any way the results obtained with the 2 methods of treatment. One hundred and three of the 147 patients affected by HSC-BPPV had the geotropic form and 44 had the apogeotropic type. We were able to transform 29 cases of HSC-BPPV from apogeotropic to geotropic. Finally, we obtained a group of 112 patients who were randomized either to the barbecue + FPP procedure (54 patients) or to the Gufoni maneuver (58 patients). The most evident result is the higher percentage of success (statistically significant) with the Gufoni maneuver at the first session of treatment (86 vs. 61%). The final control showed that 44 out of 54 (81%) patients treated with the barbecue maneuver + FPP were symptom free compared to 54 out of 58 (93%) treated with the Gufoni maneuver. Both the barbecue maneuver + FPP and the Gufoni maneuver are valid methods for treating HSC-BPPV (geotropic forms). However, our results also indicate that the Gufoni maneuver has a significant advantage: the success rate shown at the follow-up, although without statistical significance, is undoubtedly higher (93 vs. 81%). This result, together with the fact that it is very easy to perform and that patient compliance is better, make the Gufoni maneuver the method of choice in HSC-BPPV treatment.
DOI: 10.6084/m9.figshare.5121283.v1
title: Supplementary Material for: Alveolar Granulocytic Sarcoma of the Mandible in a Patient with HIV

description: <i>Background:</i> Granulocytic sarcoma (chloroma) occurs primarily in patients with acute myelogenous leukemia although it can also appear in connection with other myeloproliferative disorders. <i>Case Report:</i> We present the case of a 52-year-old human immunodeficiency virus (HIV)-positive female patient with a CD4+ count of 321 cells/ml, who developed an alveolar granulocytic sarcoma of the mandible. Pathological analysis of the tumor mass showed an infiltrate of immature cells which were positive for CD13, CD33, CD15, CD11b, and CD64, and negative for CD34, CD117, and HLA-DR. The patient achieved complete remission following a 1-week course of chemotherapy, however, 7 months later she developed a second granulocytic sarcoma in the left soleus muscle. The absolute CD4+ count had now reduced to 3 cells/ml with an inversion in the Th/Ts index (0.01), and she died of gram-negative sepsis 1 month later. Conclusions: Granulocytic sarcoma is extremely rare in patients with HIV. The case is discussed with reference to the literature.
DOI: 10.6084/m9.figshare.5121271
title: Supplementary Material for: Using a Pharmacokinetic Model to Relate an Individual’s Susceptibility to Alcohol Dependence to Genotypes

description: <i>Background/Aims:</i> Population-based studies have successfully identified genes affecting common diseases, but have not provided a molecular mechanism. We describe an approach for alcohol dependence connecting a mechanistic model at the molecular level with disease risk at the population level, and investigate how this model implies statistical gene-gene interactions that affect disease risk. <i>Methods:</i> We develop a pharmacokinetic model describing how genetic variations in <i>ADH1B</i>, <i>ADH1C</i>, <i>ADH7</i>, <i>ALDH2</i>, and <i>TAS2R38</i> affect consumption behavior, and alcohol and acetaldehyde levels over time in various tissues of individuals with a particular genotype to predict their susceptibility to alcohol dependence. <i>Results:</i> We show that there is good agreement between the observed genotype/haplotype frequencies and those predicted by the model among cases and controls. Based on this framework, we show that we expect to observe statistical interactions among these genes for a reasonably large sample size when logistic regression models are used to relate genotype effects and disease risk. <i>Conclusion:</i> Our model exemplifies mechanistic modeling of how genes interact to influence an individual’s susceptibility to alcohol dependence. We anticipate that this general approach could also be applied to study other diseases at the molecular level.
DOI: 10.6084/m9.figshare.5121274
title: Supplementary Material for: Ontogenesis of Testis Development and Function in Humans

description: Functional gonads are mandatory for sexual reproduction and survival of higher animal species. However, at the level of the individual subject, acquired or inherited gonadal dysfunction and infertility are not commonly associated with severe life-threatening phenotypes. Medical progress and increased societal interest have led to more prioritised agendas for reproductive health problems. Increasing attention is focused on disorders of sex development, fertility and sexual function. Despite this engagement, our understanding of the detailed molecular and cellular adverse events behind such problems is still incomplete. Critical early steps, such as determination of the gonads, occur at precise temporal windows of development. The sex chromosomes are obvious critical contributors, but many other human chromosomes also contribute to sex differentiation, engaging multiple genes and proteins. The aim of this review is to give an up-to-date and comprehensive summary of the events required for gonadal ontogenesis in the human male, from the stage of embryonic sex determination to postnatal maturation including puberty. The principal genes involved in these processes are tabulated and discussed. Morphological events relevant for human gonadal development are covered, in particular in connection with early germ cell maturation and spermatogenesis. Consequences of maldevelopment caused by, e.g. cryptorchidism, are discussed.
DOI: 10.6084/m9.figshare.5121277.v1
title: Supplementary Material for: Horizontal Semicircular Canal Benign Paroxysmal Positional Vertigo: Effectiveness of Two Different Methods of Treatment

description: The aim of this study is to compare the results obtained using 2 methods of treatment for horizontal semicircular canal benign paroxysmal positional vertigo (HSC-BPPV): the barbecue maneuver + forced prolonged position (FPP) versus the Gufoni maneuver. In a randomized prospective clinical trial, we recruited 147 patients affected by HSC-BPPV. The primary outcome was the absence of vertigo and nystagmus upon application of the supine roll test during the follow-up examination. A statistical evaluation was performed in order to assess whether any parameters (e.g. age, duration of nystagmus and symptoms) could influence in any way the results obtained with the 2 methods of treatment. One hundred and three of the 147 patients affected by HSC-BPPV had the geotropic form and 44 had the apogeotropic type. We were able to transform 29 cases of HSC-BPPV from apogeotropic to geotropic. Finally, we obtained a group of 112 patients who were randomized either to the barbecue + FPP procedure (54 patients) or to the Gufoni maneuver (58 patients). The most evident result is the higher percentage of success (statistically significant) with the Gufoni maneuver at the first session of treatment (86 vs. 61%). The final control showed that 44 out of 54 (81%) patients treated with the barbecue maneuver + FPP were symptom free compared to 54 out of 58 (93%) treated with the Gufoni maneuver. Both the barbecue maneuver + FPP and the Gufoni maneuver are valid methods for treating HSC-BPPV (geotropic forms). However, our results also indicate that the Gufoni maneuver has a significant advantage: the success rate shown at the follow-up, although without statistical significance, is undoubtedly higher (93 vs. 81%). This result, together with the fact that it is very easy to perform and that patient compliance is better, make the Gufoni maneuver the method of choice in HSC-BPPV treatment.
DOI: 10.6084/m9.figshare.5121268
title: Supplementary Material for: Maternal Hyperglycemia Modifies Extracellular Matrix Signaling Pathways in Neonatal Rat Lung

description: <i>Background:</i> Maternal diabetes is associated with numerous adverse effects in fetal and neonatal organs, including the lungs. <i>Objective:</i> To investigate the effects of intrauterine hyperglycemia on neonatal lung biological signaling, we performed a microarray analysis in the lungs of four 14-day-old rat pups born to a hyperglycemic dam and in four age mate control pup lungs. <i>Methods:</i> Total RNA was isolated and cDNA was hybridized to the Illumina Sentrix® RatRef-12 BeadChip. A total of 22,000 genes were analyzed for expression profiles and functional gene clustering. Ten selected genes differentially expressed in microarray were additionally analyzed by the real-time polymerase chain reaction. <i>Results:</i> Two hundred twenty-seven genes were differentially expressed in neonatal rat lungs exposed to intrauterine hyperglycemia when compared to normoglycemic controls (fold change &gt; 1.2, p &lt; 0.001). Functional clustering analysis revealed increased expression in signaling pathways involved with extracellular matrix regulation. The most significantly downregulated functions were cell proliferation, extracellular region, cell adhesion and reactive oxygen species metabolism. <i>Conclusion:</i> We found significant hyperglycemia-induced gene expression alterations in neonatal rat pulmonary tissue which may interfere with lung growth and biological signaling pathways.
DOI: 10.6084/m9.figshare.5121262
title: Supplementary Material for: Case Report and Review: Prenatal Diagnosis of Congenital Megalourethra

description: Megalourethra is a rare congenital anomaly characterized by dilatation of the penile urethra which causes functional obstruction of the lower urinary system. We present a case of congenital megalourethra diagnosed prenatally. Transabdominal sonography revealed a male fetus with bilateral hydroureter, hydronephrosis, dilated bladder and normal amniotic fluid. The fetal penis was enlarged and the penile urethra was dilated with ballooning at the distal end. The urethral meatus was identified. The fetus was delivered at term with a favorable outcome.