cometadata/datacite-titles-descriptions-related-identifiers huggingface dataset:
DOI: 10.6084/m9.figshare.5126968
title: Supplementary Material for: Does the New Staging System Proposed for Mycosis Fungoides and Sézary Syndrome Provide Reliable Agreement for T1 and T2 Disease?

description: <b><i>Background:</i></b> Patch or plaque stages in mycosis fungoides (MF) have different prognoses. The recent staging system proposed for MF discriminates between patches and plaques based upon clinical features. <b><i>Objective:</i></b> To estimate interdermatologist agreement on the morphological evaluation of MF lesions. <b><i>Methods:</i></b> Twenty-four patients with MF were enrolled. Two dermatologists evaluated every lesion face to face and independently with respect to the patch-plaque status. Cohen's κ was used to determine the rate of agreement. <b><i>Results:</i></b> Agreement was 67% with respect to the patch or plaque status [95% confidence interval (CI) = 49-85%; p &lt; 0.001]. Current systemic treatment (56%; p = 0.01) was associated with lower agreement. Younger age at diagnosis [odds ratio (OR) 1.03 (95% CI 1.02-1.05)], younger age at enrolment [OR 1.03 (95% CI 1.02-1.04)] and time on systemic treatment [OR 1.02 (95% CI 1.01-1.04)] were independent risk factors for disagreement (p &lt; 0.001). <b><i>Conclusion:</i></b> The new system for MF staging carries a significant risk of disagreement regarding patch and plaque subsets.
DOI: 10.6084/m9.figshare.5126971
title: Supplementary Material for: Adherence and Patients' Attitudes to Oral Anticancer Drugs: A Prospective Series of 201 Patients Focusing on Targeted Therapies

description: <b><i>Objectives:</i></b> Patient adherence is a challenge in oncology and hematology practice. Hormone therapy data in breast cancer suggest insufficient adherence and poor persistence. Limited data are available for targeted therapies (TT) including tyrosine kinase and mammalian target of rapamycin inhibitors. <b><i>Methods:</i></b> We performed a prospective survey using a 15-item questionnaire in patients with solid tumors and hematologic malignancies receiving oral anticancer therapy. Treatment duration, setting (adjuvant vs. metastatic), cancer type, age, and comedication were recorded. <b><i>Results:</i></b> 201 patients (median age 65.5 years) participated, 102 with TT and 99 with hormone therapy or chemotherapy (HC). The median time of drug intake was 11.0 months. Written information was more frequently given to TT patients (68.6 vs. 23.2%, p &lt; 0.0001). TT and HC patients showed equal adherence to therapy (72.5 vs. 69.6%, p = n.s.) despite TT patients experiencing more side effects (p &lt; 0.0001) and taking more concomitant oral medication (p = 0.0042). Forgotten doses were the leading cause of nonadherence in HC patients (83%, as compared to 54% in the TT group), whereas dose reduction by the patient was higher in the TT group (32 vs. 17%). <b><i>Conclusions:</i></b> Despite advances in providing information to patients leading to better adherence among TT patients, efforts towards better patient education are warranted including dedicated staff for monitoring outpatient anticancer oral therapy.
DOI: 10.6084/m9.figshare.5126974
title: Supplementary Material for: Activation of Checkpoint Kinase 2 Is Critical for Herpes Simplex Virus Type 1 Replication in Corneal Epithelium

description: <b><i>Background/Aims:</i></b> Herpes simplex virus (HSV) type I keratitis remains a leading cause of corneal morbidity, despite the availability of effective antiviral drugs. Improved understanding of virus-host interactions at the level of the host DNA damage response (DDR), a known factor in the development of HSV-1 keratitis, may shed light on potential new therapeutic targets. This report examines the role of checkpoint kinase 2 (Chk2), a DDR mediator protein, in corneal epithelial HSV-1 infection. <b><i>Methods:</i></b> A small-molecule inhibitor of Chk2 (Chk2 inhibitor II) was applied to HSV-1-infected cultured human corneal epithelial cells (hTCEpi and HCE) as well as to explanted and organotypically cultured human and rabbit corneas. Infection levels were assessed by plaque assay and real-time PCR. RNAi-mediated depletion of Chk2 was performed to confirm the effect of the inhibitor. <b><i>Results:</i></b> Inhibition of the Chk2 kinase activity greatly suppresses the cytopathic effect, genome replication and infectious progeny production in vitro and ex vivo. <b><i>Conclusion:</i></b> This report demonstrates the critical role of Chk2 kinase in the establishment of HSV-1 corneal epithelial infection. These data contribute to our understanding of herpesvirus-host interactions and underscore the significance of DDR activation in HSV-1 keratitis.
DOI: 10.6084/m9.figshare.5126965
title: Supplementary Material for: Identification of Novel Functional Null Allele of <b><i>SLC26A4</i></b> Associated with Enlarged Vestibular Aqueduct and Its Possible Implication

description: Mutations in the <i>SLC26A4</i> gene, which encodes pendrin, cause congenital hearing loss as a manifestation of Pendred syndrome (PS) with an iodide organification defect or nonsyndromic enlarged vestibular aqueduct (NSEVA, DFNB4). There have been reports of differences between PS and NSEVA, including their auditory phenotypes and molecular genetic bases. For appropriate genetic diagnosis and counseling, it is important to functionally characterize <i>SLC26A4</i> variants. In this study, we identified and evaluated a novel null mutation of <i>SLC26A4</i> and report our method of assessing the pathogenic potential of mutations in <i>SLC26A4</i>, one of the most frequent causative genes of deafness in humans. A 3-year-old female with progressive sensorineural hearing loss and her parents were recruited. They underwent clinical, audiological, radiological and genetic evaluations, which revealed that the female patient had an enlarged vestibular aqueduct and an incomplete partition type II anomaly in the cochlea bilaterally. Sanger sequencing of the <i>SLC26A4</i> gene was also performed. For a confirmatory genetic diagnosis, we first characterized the anion/base exchange ability of mutant pendrin products in HEK 293 cells and, if necessary, evaluated whether the mutant pendrin traffics to the plasma membrane in COS-7 cells. We also expressed a null function mutant, p.H723R, and a previously documented polymorphism, p.P542R, as controls. The pure tone average was 66 dB HL in the right ear and 75 dB HL in the left ear. Sequencing of <i>SLC26A4</i> revealed a known pathogenic mutation (p.H723R) and a novel missense variant (p.V510D) as a compound heterozygote. When we expressed the p.V510D mutant pendrin in mammalian cells, the rate constants for Cl<sup>-</sup>/HCO<sub>3</sub><sup>-</sup> exchange were 10.96 ± 4.79% compared with those of wild-type pendrin. This figure was comparable to that of p.H723R, indicating p.V510D to be another pathogenic mutation with a null function. The p.V510D pendrin product was shown to be entrapped in the endoplasmic reticulum (ER) at 24-30 h after transfection, and not trafficked to the plasma membrane in COS-7 cells, suggesting retention in the ER and abnormal trafficking as the pathogenic mechanism. This was similar to p.H723R, which is a null function founder mutant in this population but is a candidate variant for future drug therapy to rescue the abnormal cell trafficking. Impaired cellular trafficking due to ER retention and abolished exchange activity of the newly detected p.V510D indicates the pathogenic potential of this variant. These missense variants may be good candidate variants for drug therapy if the intrinsic exchange activity is not damaged by the change.
DOI: 10.6084/m9.figshare.5126968.v1
title: Supplementary Material for: Does the New Staging System Proposed for Mycosis Fungoides and Sézary Syndrome Provide Reliable Agreement for T1 and T2 Disease?

description: <b><i>Background:</i></b> Patch or plaque stages in mycosis fungoides (MF) have different prognoses. The recent staging system proposed for MF discriminates between patches and plaques based upon clinical features. <b><i>Objective:</i></b> To estimate interdermatologist agreement on the morphological evaluation of MF lesions. <b><i>Methods:</i></b> Twenty-four patients with MF were enrolled. Two dermatologists evaluated every lesion face to face and independently with respect to the patch-plaque status. Cohen's κ was used to determine the rate of agreement. <b><i>Results:</i></b> Agreement was 67% with respect to the patch or plaque status [95% confidence interval (CI) = 49-85%; p &lt; 0.001]. Current systemic treatment (56%; p = 0.01) was associated with lower agreement. Younger age at diagnosis [odds ratio (OR) 1.03 (95% CI 1.02-1.05)], younger age at enrolment [OR 1.03 (95% CI 1.02-1.04)] and time on systemic treatment [OR 1.02 (95% CI 1.01-1.04)] were independent risk factors for disagreement (p &lt; 0.001). <b><i>Conclusion:</i></b> The new system for MF staging carries a significant risk of disagreement regarding patch and plaque subsets.
DOI: 10.6084/m9.figshare.5126974.v1
title: Supplementary Material for: Activation of Checkpoint Kinase 2 Is Critical for Herpes Simplex Virus Type 1 Replication in Corneal Epithelium

description: <b><i>Background/Aims:</i></b> Herpes simplex virus (HSV) type I keratitis remains a leading cause of corneal morbidity, despite the availability of effective antiviral drugs. Improved understanding of virus-host interactions at the level of the host DNA damage response (DDR), a known factor in the development of HSV-1 keratitis, may shed light on potential new therapeutic targets. This report examines the role of checkpoint kinase 2 (Chk2), a DDR mediator protein, in corneal epithelial HSV-1 infection. <b><i>Methods:</i></b> A small-molecule inhibitor of Chk2 (Chk2 inhibitor II) was applied to HSV-1-infected cultured human corneal epithelial cells (hTCEpi and HCE) as well as to explanted and organotypically cultured human and rabbit corneas. Infection levels were assessed by plaque assay and real-time PCR. RNAi-mediated depletion of Chk2 was performed to confirm the effect of the inhibitor. <b><i>Results:</i></b> Inhibition of the Chk2 kinase activity greatly suppresses the cytopathic effect, genome replication and infectious progeny production in vitro and ex vivo. <b><i>Conclusion:</i></b> This report demonstrates the critical role of Chk2 kinase in the establishment of HSV-1 corneal epithelial infection. These data contribute to our understanding of herpesvirus-host interactions and underscore the significance of DDR activation in HSV-1 keratitis.
DOI: 10.6084/m9.figshare.5126959
title: Supplementary Material for: De novo Structure Variations of the Y Chromosome in a 47,XXY Female with Ovarian Failure: A Case Report

description: We report on a patient with a 47,XXY karyotype who presents a normal female phenotype, which is an extremely rare observation worldwide. The patient is infertile. Type B ultrasound scans and other tests suggested that her ovaries had completely failed. Microsatellite DNA marker analysis revealed that the 2 X chromosomes were derived from her mother and that this abnormality was caused by non-disjunction of the maternal X chromosomes during meiosis II. Copy number variation analysis identified 2 large de novo deletions in her Y chromosome. Remarkably, one of the deleted regions includes the <i>SRY</i> gene locus, which might explain her female phenotype. However, the genetic mechanism of her ovarian failure remains unclear. This paper is the first report of a 47,XXY female with ovarian failure.
DOI: 10.6084/m9.figshare.5126956
title: Supplementary Material for: Demonstration of the Pericallosal Artery at 11-13 Weeks of Gestation Using 3D Ultrasound

description: <b><i>Objective:</i></b> To assess the sonographic visualization of the pericallosal arteries in normal fetuses at 11-13 weeks of gestation using 3D ultrasound. <b><i>Methods:</i></b> We prospectively enrolled women with a singleton pregnancy undergoing ultrasound at 11-13 weeks of gestation. A 3D volume with high-definition power Doppler was acquired starting from the sagittal view of the fetal head and stored in the spatiotemporal image correlation mode. The images of the pericallosal arteries were assigned a score of 0 (no visualization), 1 (visualization of the origin) or 2 (visualization of the whole course). A follow-up scan was performed in all cases at 20 weeks of gestation to assess the presence of the corpus callosum. <b><i>Results:</i></b> 70 patients were included and the pericallosal arteries were sonographically detectable in all cases. Image scores of 1 and 2 were obtained in 8 and 62 cases, respectively. The whole length of the vessel was between 3.5 and 4.5 mm. The vast majority of those with a score of 2 were beyond 12 completed weeks of gestation. All fetuses showed a normal corpus callosum at midtrimester and no abnormal brain findings after birth. <b><i>Conclusions:</i></b> The pericallosal arteries are sonographically visible since the first trimester in 3D ultrasound scans of fetuses found to have a normal corpus callosum at follow-up.
DOI: 10.6084/m9.figshare.5126962
title: Supplementary Material for: Personal Genomics in Greece: An Overview of Available Direct-to-Consumer Genomic Services and the Relevant Legal Framework

description: <b><i>Background:</i></b> This article provides an overview of direct-to-consumer (DTC) genomic services that are currently available in Greece and the legal framework within which they operate. <b><i>Methods:</i></b> Here, we describe the landscape of the DTC genomic testing companies and laboratories by conducting a systematic Ιnternet search for relevant websites. We examine the existing legal framework regarding genetic testing in Greece by a review of present regulation. Although Greece does not have explicit legal provisions for DTC genomics, several other laws, including soft law mechanisms, create the broader legal framework within which DTC genomic services may exist. <b><i>Results/Conclusions:</i></b> While the current legal framework creates a flexible environment that is conducive to DTC genomic operations, it is also ambiguous about the legality of some specific services. Given the growing DTC activity in Greece, we argue that it is important to both enforce compliance with existing law and clarify legal ambiguities that may risk limiting the power of legal protections that ought to be afforded to consumers.
DOI: 10.6084/m9.figshare.5126965.v1
title: Supplementary Material for: Identification of Novel Functional Null Allele of <b><i>SLC26A4</i></b> Associated with Enlarged Vestibular Aqueduct and Its Possible Implication

description: Mutations in the <i>SLC26A4</i> gene, which encodes pendrin, cause congenital hearing loss as a manifestation of Pendred syndrome (PS) with an iodide organification defect or nonsyndromic enlarged vestibular aqueduct (NSEVA, DFNB4). There have been reports of differences between PS and NSEVA, including their auditory phenotypes and molecular genetic bases. For appropriate genetic diagnosis and counseling, it is important to functionally characterize <i>SLC26A4</i> variants. In this study, we identified and evaluated a novel null mutation of <i>SLC26A4</i> and report our method of assessing the pathogenic potential of mutations in <i>SLC26A4</i>, one of the most frequent causative genes of deafness in humans. A 3-year-old female with progressive sensorineural hearing loss and her parents were recruited. They underwent clinical, audiological, radiological and genetic evaluations, which revealed that the female patient had an enlarged vestibular aqueduct and an incomplete partition type II anomaly in the cochlea bilaterally. Sanger sequencing of the <i>SLC26A4</i> gene was also performed. For a confirmatory genetic diagnosis, we first characterized the anion/base exchange ability of mutant pendrin products in HEK 293 cells and, if necessary, evaluated whether the mutant pendrin traffics to the plasma membrane in COS-7 cells. We also expressed a null function mutant, p.H723R, and a previously documented polymorphism, p.P542R, as controls. The pure tone average was 66 dB HL in the right ear and 75 dB HL in the left ear. Sequencing of <i>SLC26A4</i> revealed a known pathogenic mutation (p.H723R) and a novel missense variant (p.V510D) as a compound heterozygote. When we expressed the p.V510D mutant pendrin in mammalian cells, the rate constants for Cl<sup>-</sup>/HCO<sub>3</sub><sup>-</sup> exchange were 10.96 ± 4.79% compared with those of wild-type pendrin. This figure was comparable to that of p.H723R, indicating p.V510D to be another pathogenic mutation with a null function. The p.V510D pendrin product was shown to be entrapped in the endoplasmic reticulum (ER) at 24-30 h after transfection, and not trafficked to the plasma membrane in COS-7 cells, suggesting retention in the ER and abnormal trafficking as the pathogenic mechanism. This was similar to p.H723R, which is a null function founder mutant in this population but is a candidate variant for future drug therapy to rescue the abnormal cell trafficking. Impaired cellular trafficking due to ER retention and abolished exchange activity of the newly detected p.V510D indicates the pathogenic potential of this variant. These missense variants may be good candidate variants for drug therapy if the intrinsic exchange activity is not damaged by the change.
DOI: 10.6084/m9.figshare.5126953
title: Supplementary Material for: Repeated Premature Hemofilter Clotting During Regional Citrate Anticoagulation as Indicator of Heparin Induced Thrombocytopenia

description: <b><i>Purpose:</i></b> Early clinical signs of heparin induced thrombocytopenia (HIT) are nonspecific and include a sudden drop in the number of platelets as well as formation of arterial and venous thromboses. Regional citrate anticoagulation (RCA) is increasingly used as a very effective modality to prevent filter clotting during renal replacement therapy (RRT). We report the first case where repeated premature filter clotting despite RCA indicated a manifestation of HIT. <b><i>Materials and Methods:</i></b> A 71-year old woman admitted to the ICU for a compartment syndrome of the leg developed septic shock with acute kidney injury requiring continuous veno-venous hemodialysis (CVVHD). Because of unexpected and repeated premature filter clotting during CVVHD using RCA, HIT was suspected. <b><i>Results:</i></b> The diagnosis of HIT was confirmed by the presence of IgG antibodies against heparin and platelet factor (PF) 4 complexes and six points in the 4T score. Discontinuation of heparin administration and initiation of systemic anticoagulation with danaparoid sodium resulted in the normalization of platelet count and hemofilter lifetime. <b><i>Conclusion:</i></b> RCA does not seem to be sufficient to prevent hemofilter clotting during HIT. Thus, in case of repeated premature filter clotting despite RCA, one should suspect HIT and prompt diagnostic workup as well as a switch to alternative anticoagulation. i 2014 S. Karger AG, Basel
DOI: 10.6084/m9.figshare.5126959.v1
title: Supplementary Material for: De novo Structure Variations of the Y Chromosome in a 47,XXY Female with Ovarian Failure: A Case Report

description: We report on a patient with a 47,XXY karyotype who presents a normal female phenotype, which is an extremely rare observation worldwide. The patient is infertile. Type B ultrasound scans and other tests suggested that her ovaries had completely failed. Microsatellite DNA marker analysis revealed that the 2 X chromosomes were derived from her mother and that this abnormality was caused by non-disjunction of the maternal X chromosomes during meiosis II. Copy number variation analysis identified 2 large de novo deletions in her Y chromosome. Remarkably, one of the deleted regions includes the <i>SRY</i> gene locus, which might explain her female phenotype. However, the genetic mechanism of her ovarian failure remains unclear. This paper is the first report of a 47,XXY female with ovarian failure.
DOI: 10.6084/m9.figshare.5126950
title: Supplementary Material for: Self-Disorder and Brain Processing of Proprioception in Schizophrenia Spectrum Patients: A Re-Analysis

description: <b><i>Background:</i></b> Anomalies of self-awareness (self-disorders, SDs) are theorized to be basic to schizophrenia psychopathology. We have previously observed dysfunction of brain processing of proprioception in schizophrenia spectrum disorders (SZS). We hypothesized that SDs could be associated with abnormalities of early contralateral proprioceptive evoked oscillatory brain activity. <b><i>Methods:</i></b> We investigated the association between proprioceptive evoked potential components and SDs in a re-analysis of data from a subsample (n = 12) of SZS patients who had previously been observed with deviant proprioceptive evoked potentials and interviewed with the Examination of Anomalous Self-Experience (EASE) scale. <b><i>Results:</i></b> Higher EASE scores (i.e. increased SD) were associated with lower peak parietal gamma frequencies and higher peak beta amplitudes over frontal and parietal electrodes in the left hemisphere following right-hand proprioceptive stimulation. <b><i>Conclusion:</i></b> Disorders of self-awareness may be associated with dysfunction of early phases of somatosensory processing. The findings are potentially relevant to our understanding of the pathophysiology of schizophrenia, but further studies are needed.
DOI: 10.6084/m9.figshare.5126956.v1
title: Supplementary Material for: Demonstration of the Pericallosal Artery at 11-13 Weeks of Gestation Using 3D Ultrasound

description: <b><i>Objective:</i></b> To assess the sonographic visualization of the pericallosal arteries in normal fetuses at 11-13 weeks of gestation using 3D ultrasound. <b><i>Methods:</i></b> We prospectively enrolled women with a singleton pregnancy undergoing ultrasound at 11-13 weeks of gestation. A 3D volume with high-definition power Doppler was acquired starting from the sagittal view of the fetal head and stored in the spatiotemporal image correlation mode. The images of the pericallosal arteries were assigned a score of 0 (no visualization), 1 (visualization of the origin) or 2 (visualization of the whole course). A follow-up scan was performed in all cases at 20 weeks of gestation to assess the presence of the corpus callosum. <b><i>Results:</i></b> 70 patients were included and the pericallosal arteries were sonographically detectable in all cases. Image scores of 1 and 2 were obtained in 8 and 62 cases, respectively. The whole length of the vessel was between 3.5 and 4.5 mm. The vast majority of those with a score of 2 were beyond 12 completed weeks of gestation. All fetuses showed a normal corpus callosum at midtrimester and no abnormal brain findings after birth. <b><i>Conclusions:</i></b> The pericallosal arteries are sonographically visible since the first trimester in 3D ultrasound scans of fetuses found to have a normal corpus callosum at follow-up.