cometadata/datacite-titles-descriptions-related-identifiers huggingface dataset:
DOI: 10.6084/m9.figshare.5126695.v1
title: Supplementary Material for: Congenital Adrenal Hyperplasia, Ovarian Failure and Ehlers-Danlos Syndrome due to a 6p Deletion

description: Cryptic deletions in balanced de novo translocations represent a frequent cause of abnormal phenotypes, including Mendelian diseases. In this study, we describe a patient with multiple congenital abnormalities, such as late-onset congenital adrenal hyperplasia (CAH), primary ovarian failure and Ehlers-Danlos syndrome (EDS), who carries a de novo t(6;14)(p21;q32) translocation. Genomic array analysis identified a cryptic 1.1-Mb heterozygous deletion, adjacent to the breakpoint on chromosome 6, extending from 6p21.33 to 6p21.32 and affecting 85 genes, including <i>CYP21A2,</i><i>TNXB</i> and <i>MSH5</i>. Multiplex ligation-dependent probe amplification analysis of the 6p21.3 region was performed in the patient and her family and revealed a 30-kb deletion in the patient's normal chromosome 6, inherited from her mother, resulting in homozygous loss of genes <i>CYP21A1P</i> and <i>C4B</i>. <i>CYP21A2 </i>sequencing showed that its promoter region was not affected by the 30-kb deletion, suggesting that the deletion of other regulatory sequences in the normal chromosome 6 caused a loss of function of the <i>CYP21A2</i> gene. EDS and primary ovarian failure phenotypes could be explained by the loss of genes <i>TNXB</i> and <i>MSH5</i>, a finding that may contribute to the characterization of disease-causing genes. The detection of this de novo microdeletion drastically reduced the estimated recurrence risk for CAH in the family.
DOI: 10.6084/m9.figshare.5126674
title: Supplementary Material for: The Risk of Ischemic Stroke after an Acute Myocardial Infarction in Patients with Decreased Renal Function

description: <b><i>Background:</i></b> Data on the incidence, trends over time and predictors of ischemic stroke after an acute myocardial infarction (AMI) are sparse for patients with chronic kidney disease (CKD). <b><i>Methods:</i></b> Data for unselected AMI patients were obtained from the Swedish Register of Information and Knowledge about Swedish Heart Intensive Care Admissions (RIKS-HIA) between 2003 and 2010. Patients with and without CKD were compared. Multiple logistic regression was performed to identify predictors of ischemic stroke during the hospitalization for AMI, Kaplan-Meier analysis was used to analyze the 1-year postdischarge ischemic stroke trends over time and Cox regression analysis was used to identify predictors. <b><i>Results:</i></b> Of 118,434 AMI patients, 40,679 had CKD. The CKD patients had more extensive previous cardiovascular disease and received less reperfusion and secondary preventive therapies than the patients without CKD. An inhospital ischemic stroke occurred in 2.3 and 1.2% of CKD and non-CKD patients, respectively. The incidence of ischemic stroke during hospitalization for AMI was stable during the study period. The occurrence of ischemic stroke after hospital discharge decreased between 2003-2004 and 2009-2010 from 4.1 to 2.5% in CKD patients and from 2.0 to 1.3% in non-CKD patients, respectively. Percutaneous coronary intervention (PCI) and statins were independently associated with a reduced risk of stroke after discharge from hospital. <b><i>Conclusions:</i></b> Ischemic stroke is a more common complication after an AMI in CKD patients than in non-CKD patients, but the risk has decreased in recent years. The increased use of PCI and statins may have contributed to this reduction.
DOI: 10.6084/m9.figshare.5126683.v1
title: Supplementary Material for: Direct Evidence for Self-Propagation of Different Amyloid-β Fibril Conformations

description: <b><i>Background:</i></b> Amyloid fibrils formed by amyloid-β (Aβ) peptides are associated with Alzheimer's disease and can occur in a range of distinct morphologies that are not uniquely determined by the Aβ sequence. Whether distinct conformations of Aβ fibrils can be stably propagated over multiple cycles of seeding and fibril growth has not been established experimentally. <b><i>Objective:</i></b> The ability of the 40-residue peptide Aβ<sub>1-40</sub> to assemble into fibrils with the conformation of the mutant Aβ<sub>1-40</sub> peptide containing the ‘Osaka' mutation E22Δ was investigated. <b><i>Methods:</i></b> Fibril formation of highly pure, recombinant Aβ<sub>1-40</sub> in the presence of distinct, preformed seeds in vitro was recorded with thioflavin T fluorescence, and distinct fibrillar structures were identified and distinguished by fluorescence spectroscopy and electron microscopy. <b><i>Results:</i></b> We propagated the specific quaternary structure of Aβ<sub>1-40</sub> E22Δ fibrils with wild-type Aβ<sub>1-40</sub> over up to seven cycles of seeding and fibril elongation. As a result of a 10<sup>7</sup>-fold dilution of the initially present Aβ<sub>1-40</sub> E22Δ seeds, the vast majority of fibrils formed after the seventh propagation cycle with Aβ<sub>1-40</sub> did not contain a single molecule of Aβ<sub>1-40</sub> E22Δ, but still retained the conformation of the initial Aβ<sub>1-40</sub> E22Δ seeds. Increased critical concentrations of Aβ<sub>1-40</sub> fibrils formed in the presence of Aβ<sub>1-40</sub> E22Δ nuclei suggest that these fibrils are less stable than homologously seeded Aβ<sub>1-40</sub> fibrils, consistent with a kinetically controlled mechanism of fibril formation. <b><i>Conclusion:</i></b> The propagation of a distinct Aβ fibril conformation over multiple cycles of seeded fibril growth demonstrates the basic ability of the Aβ peptide to form amyloid strains that in turn may cause phenotypes in Alzheimer's disease.
DOI: 10.6084/m9.figshare.5126668
title: Supplementary Material for: Improving Outcome after Pancreaticoduodenectomy: Experiences with Implementing an Enhanced Recovery After Surgery (ERAS) Program

description: <b><i>Background:</i></b> Pancreaticoduodenectomies (PDs) are complex surgical procedures that require high-standard perioperative care. The objective of this study was to evaluate the effects of implementing an Enhanced Recovery After Surgery (ERAS) program for PD on patient outcome. <b><i>Methods:</i></b> 230 patients undergoing PD in the Maastricht University Medical Centre between January 1995 and January 2012 were included. Group 1 (no ERAS; 1995-2005) received traditional care. From January 2006, several elements of an ERAS pathway for pancreatic surgery were implemented (group 2: ‘ERAS-like'). From 2009 onwards the ERAS pathway was fully implemented (group 3: ERAS). Mortality, complications, readmissions and length of hospital stay (LOS) were evaluated in the subgroups and compared. <b><i>Results:</i></b> Median LOS was significantly reduced from 20 days in group 1 to 13 days in group 2 and 14 days in group 3 (p = 0.001). Median LOS of patients without complications was 16, 10 and 9 days in groups 1, 2 and 3, respectively (p &lt; 0.0001). Over time, the average age of patients undergoing PD increased significantly. Complication rates as well as mortality and readmission rates did not change over time. <b><i>Conclusion:</i></b> Implementing an ERAS program contributed to a decrease of LOS without compromising other outcomes. Mortality, morbidity and readmission rates stayed unchanged and more complications were managed non-operatively.
DOI: 10.6084/m9.figshare.5126671
title: Supplementary Material for: Overexpressed NLRC3 Acts as an Anti-Inflammatory Cytosolic Protein

description: The novel nucleotide oligomerization domain (NOD)-like receptor (NLR) with a caspase activation and recruitment domain (CARD) 3 (NLRC3) protein belongs to the NLR family of cytosolic pathogen recognition receptors. NLRC3 has the characteristic NOD and leucine-rich repeat configuration with a less well defined CARD. T lymphocytes are known to have high NLRC3 expression, which may be involved in suppression of T cell activation. Here, we report that NLRC3 is a cytoplasmic protein that negatively regulates pro-IL-1β maturation. Among well-known inflammasome components, NLRC3 can interact with apoptosis-associated speck-like protein containing a CARD (ASC) and caspases 1 and 5. Transient transfection of NLRC3 into stable EGFP-ASC-expressing HEK293FT cells reduces NLR family, pyrin domain-containing 3 (NLRP3)/cryopyrin-induced formation of ASC specks in a dose- and time-dependent manner. This suggests that NLRC3 can regulate ASC speck formation, caspase-1 activation and IL-1β maturation. We show for the first time that inflammasome-like complexes assemble when caspase-1 and ASC are cotransfected together with NLRC3 in HEK293FT cells. However, overexpression of NLRC3 with NLRP3/cryopyrin inflammasome components suppresses pro-caspase-1 cleavage and IL-1β processing. Our study suggests that NLRC3 negatively regulates inflammatory responses.
DOI: 10.6084/m9.figshare.5126674.v1
title: Supplementary Material for: The Risk of Ischemic Stroke after an Acute Myocardial Infarction in Patients with Decreased Renal Function

description: <b><i>Background:</i></b> Data on the incidence, trends over time and predictors of ischemic stroke after an acute myocardial infarction (AMI) are sparse for patients with chronic kidney disease (CKD). <b><i>Methods:</i></b> Data for unselected AMI patients were obtained from the Swedish Register of Information and Knowledge about Swedish Heart Intensive Care Admissions (RIKS-HIA) between 2003 and 2010. Patients with and without CKD were compared. Multiple logistic regression was performed to identify predictors of ischemic stroke during the hospitalization for AMI, Kaplan-Meier analysis was used to analyze the 1-year postdischarge ischemic stroke trends over time and Cox regression analysis was used to identify predictors. <b><i>Results:</i></b> Of 118,434 AMI patients, 40,679 had CKD. The CKD patients had more extensive previous cardiovascular disease and received less reperfusion and secondary preventive therapies than the patients without CKD. An inhospital ischemic stroke occurred in 2.3 and 1.2% of CKD and non-CKD patients, respectively. The incidence of ischemic stroke during hospitalization for AMI was stable during the study period. The occurrence of ischemic stroke after hospital discharge decreased between 2003-2004 and 2009-2010 from 4.1 to 2.5% in CKD patients and from 2.0 to 1.3% in non-CKD patients, respectively. Percutaneous coronary intervention (PCI) and statins were independently associated with a reduced risk of stroke after discharge from hospital. <b><i>Conclusions:</i></b> Ischemic stroke is a more common complication after an AMI in CKD patients than in non-CKD patients, but the risk has decreased in recent years. The increased use of PCI and statins may have contributed to this reduction.
DOI: 10.6084/m9.figshare.5126659
title: Supplementary Material for: Staging of Primary Breast Cancer Is not Indicated in Asymptomatic Patients with Early Tumor Stages

description: <b><i>Background: </i></b>The routinely practiced staging for distant metastasis in patients with primary breast cancer has been increasingly questioned. <b><i>Patients and Methods: </i></b>Data from 742 patients with breast cancer who had completed staging (chest x-ray, liver ultrasound, and bone scan) were retrospectively analyzed. Present findings were transferred to a dataset of a voluntarily monitored benchmarking project by the West German Breast Center that included patient data of 179 breast cancer centers. <b><i>Results: </i></b>Routine staging examinations revealed in 1.2% (n = 9) distant metastasis and in 38.8% (n = 288) suspicious results. In total, 15 patients (2%) had distant metastases confirmed by additional diagnostics. The existence of distant metastases correlated with tumor size, nodal state, and lymphatic vessel spread. Tumor size and nodal state were independent predictors for disseminated disease. The risk of exhibiting distant metastases was 0.77% for patients with tumor stage pT1 pN1. Based on these findings, in 159,310 patients 41,728 chest x-rays, 43,950 liver ultrasounds, and 39,037 bone scans could have been avoided. <b><i>Conclusion: </i></b>Asymptomatic patients with tumor stages ≤ pT1 pN1 do not benefit from staging of primary breast cancer. Suspending staging examinations for these patients could reduce cost without restricting oncologic safety.
DOI: 10.6084/m9.figshare.5126662
title: Supplementary Material for: The Microscopic Complexities of C3 in Breast Cytology

description: <b><i>Background:</i></b> Fine-needle aspiration (FNA) of difficult breast lesions often results in an atypical (C3) report. The assortment of outcomes generated by C3 reports varies widely, and this has given rise to different clinical management pathways. <b><i>Objective:</i></b> To identify and objectively assess microscopic features associated with atypical/C3 breast FNA cases. <b><i>Materials and Methods:</i></b> A total of 230 atypical breast FNAs were subjected to a blind microscopic rescreen using a range of robust qualitative and quantitative cytological criteria including cellularity, architectural qualities, cytomorphology and background features. A logistic regression with a receiver operating characteristic (ROC) curve and the resultant forward stepwise analysis were conducted to assess the results. This statistical testing was measured against malignant, benign proliferative and benign non-proliferative outcomes. <b><i>Results:</i></b> The malignant and benign proliferative outcomes showed a mixture of opposing protective and predictive individual cytological criteria. The stepwise analysis produced models demonstrating the best combination of individual cytological criteria for malignancy, proliferative and benign non-proliferative entities. In the malignancy model, discohesion, nuclear crowding within sheets, diminished numbers of bare bipolar nuclei and myoepithelial cells, the presence of tubules or necrosis and the absence of a cystic background were important features. The benign proliferative model suggested the same criteria but with the opposite implication and with the addition of several others, such as the presence of apocrine metaplasia, retained polarity and a speckled or coarse chromatin pattern. Age was a significant factor in malignant and proliferative outcomes. The benign non-proliferative stepwise analysis produced a model with fewer criteria (complex sheets, bare bipolar nuclei and a cystic background) limiting clinical application. <b><i>Conclusion:</i></b> Atypical/C3 breast cytology remains a legitimate reporting category. However, it is associated with a number of different histological outcomes. The incidence of the C3 category can be significantly reduced by controlling extrinsic factors and understanding the associated microscopic features.
DOI: 10.6084/m9.figshare.5126665
title: Supplementary Material for: Depression and All-Cause Mortality in Hemodialysis Patients

description: <b><i>Background:</i></b> There are limited data regarding the relationship between depression and mortality in hemodialysis (HD) patients. <b><i>Methods:</i></b> Among 323 patients receiving maintenance HD, depression symptoms were assessed using the Center for Epidemiologic Studies Depression (CES-D) scale, with a score of ≥16 consistent with depression. Adjusted Cox proportional-hazards models with additional analyses incorporating antidepressant medication use were used to evaluate the association between depression and mortality. Baseline CES-D scores were used for the primary analyses, while secondary time-dependent analyses incorporated subsequent CES-D results. <b><i>Results:</i></b> The mean age was 62.9 ± 16.5 years, 46% of the subjects were women and 22% were African-American. The mean baseline CES-D score was 10.7± 8.3, and 83 (26%) participants had CES-D scores ≥16. During a median (25th, 75th) follow-up of 25 (13, 43) months, 154 participants died. After adjusting for age, sex, race, primary cause of kidney failure, dialysis vintage and access, baseline depression was associated with an increased risk of all-cause mortality (HR 1.51 and 95% CI 1.06-2.17). This attenuated with further adjustment for cardiovascular disease, smoking, Kt/V, serum albumin, log C-reactive protein and use of antidepressants (HR 1.21 and 95% CI 0.82-1.80). When evaluating time-dependent CES-D, depression remained associated with increased mortality risk in the fully adjusted model (HR 1.44 and 95% CI 1.00-2.06). <b><i>Conclusions:</i></b> Greater symptoms of depression are associated with an increased risk of mortality in HD patients, particularly when accounting for the most proximate assessment. This relationship was attenuated with adjustment for comorbid conditions, suggesting a complex relationship between clinical characteristics and depression symptoms. Future studies should evaluate whether treatment for depression impacts mortality among HD patients.
DOI: 10.6084/m9.figshare.5126671.v1
title: Supplementary Material for: Overexpressed NLRC3 Acts as an Anti-Inflammatory Cytosolic Protein

description: The novel nucleotide oligomerization domain (NOD)-like receptor (NLR) with a caspase activation and recruitment domain (CARD) 3 (NLRC3) protein belongs to the NLR family of cytosolic pathogen recognition receptors. NLRC3 has the characteristic NOD and leucine-rich repeat configuration with a less well defined CARD. T lymphocytes are known to have high NLRC3 expression, which may be involved in suppression of T cell activation. Here, we report that NLRC3 is a cytoplasmic protein that negatively regulates pro-IL-1β maturation. Among well-known inflammasome components, NLRC3 can interact with apoptosis-associated speck-like protein containing a CARD (ASC) and caspases 1 and 5. Transient transfection of NLRC3 into stable EGFP-ASC-expressing HEK293FT cells reduces NLR family, pyrin domain-containing 3 (NLRP3)/cryopyrin-induced formation of ASC specks in a dose- and time-dependent manner. This suggests that NLRC3 can regulate ASC speck formation, caspase-1 activation and IL-1β maturation. We show for the first time that inflammasome-like complexes assemble when caspase-1 and ASC are cotransfected together with NLRC3 in HEK293FT cells. However, overexpression of NLRC3 with NLRP3/cryopyrin inflammasome components suppresses pro-caspase-1 cleavage and IL-1β processing. Our study suggests that NLRC3 negatively regulates inflammatory responses.
DOI: 10.6084/m9.figshare.5126650
title: Supplementary Material for: Cutaneous or Respiratory Exposures to Peanut Allergens in Mice and Their Impacts on Subsequent Oral Exposure

description: <b><i>Background:</i></b> Recent data suggested that non-gastrointestinal exposure can lead to sensitisation to food allergens. We thus assessed the immune impact of respiratory or cutaneous exposure to peanut proteins on non-altered epithelium and investigated the effect of such pre-exposure on subsequent oral administration of peanut. <b><i>Methods:</i></b> BALB/cJ<b> </b>mice were exposed to purified Ara h 1 or to a non-defatted roasted peanut extract (PE) by simple deposit of allergens solutions on non-altered skin or in the nostrils. Exposures were performed 6 times at weekly intervals. Pre-exposed mice then received intra-gastric administrations of PE alone or in the presence of the Th2 mucosal adjuvant cholera toxin (CT). The specific humoral and cellular immune response was assessed throughout the protocol. <b><i>Results:</i></b> Both<b> </b>cutaneous and respiratory exposures led to the production of specific IgG1. Local and systemic IL-5 and IL-13 production were also evidenced, demonstrating activation of specific Th2 cells. This effect was dose-dependent and most efficient via the respiratory route. Moreover, these pre-exposures led to the production of specific IgE antibodies after gavage with PE, whatever the presence of CT. <b><i>Conclusions:</i></b> Cutaneous or respiratory exposures to peanut induce Th2 priming in mice. Moreover, pre-exposures promote further sensitisation via the oral route without the use of CT; this proposes a new adjuvant-free experimental model of sensitisation to food that may reflect a realistic exposure pattern in infants. These results also suggest that non-gastrointestinal peanut exposure should be minimised in high-risk infants, even those with non-altered skin, to potentially reduce allergic sensitisation to this major food allergen.
DOI: 10.6084/m9.figshare.5126656
title: Supplementary Material for: The Impact of a Tumor Diagnosis on Patients' Attitudes toward Advance Directives

description: <b><i>Background:</i></b> Although advance care planning and the completion of advance directives (ADs) are important tools to avoid unwanted aggressive care once patients have lost their decision-making capacity, only a minority of cancer patients are admitted with completed ADs, and little is known about patients' wishes regarding AD consultations. <b><i>Methods:</i></b> For 1 year, every new patient admitted to the hematology/oncology outpatient clinic of the University Hospital Regensburg received a self-administered questionnaire comprising a self-evaluation of AD knowledge and questions about preferences regarding consultation partners and the time of consultation. Disease-related data were collected from medical records. Statistics were calculated with SPSS. <b><i>Results:</i></b> Of the 500 questionnaires handed out, 394 (75%) were evaluable and analyzed. Twenty-eight percent of the participants had completed an AD (living will or health care proxy). Ninety-two percent of the participants without ADs had never received a consultation offer from any professional involved. Only 20% perceived a clear relation between cancer and AD consultations. More than 50% of the participants without ADs were in favor of consultations ‘now' or ‘in a few weeks', while more than 40% objected to AD consultations. <b><i>Conclusions:</i></b> Oncology patients have a large unmet demand for AD consultations. However, a relevant percentage of these patients object to AD consultations. Structured and early AD consultation offers should be made, and early discussions about indications for aggressive treatment should take place.
DOI: 10.6084/m9.figshare.5126659.v1
title: Supplementary Material for: Staging of Primary Breast Cancer Is not Indicated in Asymptomatic Patients with Early Tumor Stages

description: <b><i>Background: </i></b>The routinely practiced staging for distant metastasis in patients with primary breast cancer has been increasingly questioned. <b><i>Patients and Methods: </i></b>Data from 742 patients with breast cancer who had completed staging (chest x-ray, liver ultrasound, and bone scan) were retrospectively analyzed. Present findings were transferred to a dataset of a voluntarily monitored benchmarking project by the West German Breast Center that included patient data of 179 breast cancer centers. <b><i>Results: </i></b>Routine staging examinations revealed in 1.2% (n = 9) distant metastasis and in 38.8% (n = 288) suspicious results. In total, 15 patients (2%) had distant metastases confirmed by additional diagnostics. The existence of distant metastases correlated with tumor size, nodal state, and lymphatic vessel spread. Tumor size and nodal state were independent predictors for disseminated disease. The risk of exhibiting distant metastases was 0.77% for patients with tumor stage pT1 pN1. Based on these findings, in 159,310 patients 41,728 chest x-rays, 43,950 liver ultrasounds, and 39,037 bone scans could have been avoided. <b><i>Conclusion: </i></b>Asymptomatic patients with tumor stages ≤ pT1 pN1 do not benefit from staging of primary breast cancer. Suspending staging examinations for these patients could reduce cost without restricting oncologic safety.