In this task, you are given a passage which has a question and the context. You have to generate an answer to the question based on the information present in the context.

Ex Input:
Context: For the majority of congenital heart diseases (CHDs), the full complexity of the causative molecular network, which is driven by genetic, epigenetic, and environmental factors, is yet to be elucidated. Epigenetic alterations are suggested to play a pivotal role in modulating the phenotypic expression of CHDs and their clinical course during life. Candidate approaches implied that DNA methylation might have a developmental role in CHD and contributes to the long-term progress of non-structural cardiac diseases. The aim of the present study is to define the postnatal epigenome of two common cardiac malformations, representing epigenetic memory, and adaption to hemodynamic alterations, which are jointly relevant for the disease course.', 'We present the first analysis of genome-wide DNA methylation data obtained from myocardial biopsies of Tetralogy of Fallot (TOF) and ventricular septal defect patients. We defined stringent sets of differentially methylated regions between patients and controls, which are significantly enriched for genomic features like promoters, exons, and cardiac enhancers. For TOF, we linked DNA methylation with genome-wide expression data and found a significant overlap for hypermethylated promoters and down-regulated genes, and vice versa. We validated and replicated the methylation of selected CpGs and performed functional assays. We identified a hypermethylated novel developmental CpG island in the promoter of SCO2 and demonstrate its functional impact. Moreover, we discovered methylation changes co-localized with novel, differential splicing events among sarcomeric genes as well as transcription factor binding sites. Finally, we demonstrated the interaction of differentially methylated and expressed genes in TOF with mutated CHD genes in a molecular network.\Question: Does comparative DNA methylation and gene expression analysis identify novel genes for structural congenital heart diseases?

Ex Output:
By interrogating DNA methylation and gene expression data, we identify two novel mechanism contributing to the phenotypic expression of CHDs: aberrant methylation of promoter CpG islands and methylation alterations leading to differential splicing.


Ex Input:
Context: To describe the findings of enhanced depth imaging (EDI) optical coherence tomography (OCT) of the lamina cribrosa (LC) in glaucoma and pachychoroid spectrum diseases associated with peripapillary retinoschisis.', 'Retrospective, observational case series.', 'A total of 16 patients from 1 institution.', 'Detailed medical case histories, optic disc and retinal imaging with EDI using the Spectralis OCT (Heidelberg Engineering, Heidelberg, Germany), and clinical course were reviewed for patients with peripapillary retinoschisis without a known predisposing condition.', 'Clinical features and findings of the EDI OCT.', 'Among the 16 eyes with peripapillary retinoschisis that had abnormal findings on EDI of the LC, 8 had glaucoma and 8 had pachychoroid spectrum diseases, including chronic central serous chorioretinopathy (CSC) (6 eyes), small pigment epithelium detachment (1 eye), and polypoidal choroidal vasculopathy (PCV) (1 eye). The abnormal LC findings were central or peripheral focal LC defects in eyes with glaucoma and LC disinsertions or peripheral focal LC defects in eyes with pachychoroid spectrum diseases. Central LC defects were related to inner layer retinoschisis, whereas LC disinsertions and peripheral LC defects were related to outer layer retinoschisis. The peripapillary retinoschisis did not show a topographic association with the underlying chronic CSC- or PCV-associated lesions. In 6 treated eyes with pachychoroid, peripapillary retinoschisis resolved along with subretinal fluid after anti-vascular endothelial growth factor injection in 4 eyes, whereas retinoschisis persisted after the resolution of subretinal fluid in 2 eyes.\Question: Do alterations of the Lamina Cribrosa Are Associated with Peripapillary Retinoschisis in Glaucoma and Pachychoroid Spectrum Disease?

Ex Output:
Enhanced depth imaging OCT of the LC demonstrated alterations associated with peripapillary retinoschisis, pachychoroid spectrum diseases, and glaucoma.


Ex Input:
Context: Two-stage revision surgery for infected total hip arthroplasty (THA) is commonly advocated, but substantial morbidity and expense are associated with this technique. In certain cases of infected THA, treatment with one-stage revision surgery and intraarticular infusion of antibiotics may offer a reasonable alternative with the distinct advantage of providing a means of delivering the drug in high concentrations.', 'We describe a protocol for intraarticular delivery of antibiotics to the hip through an indwelling catheter combined with one-stage revision surgery and examine (1) the success as judged by eradication of infection at 1 year when treating chronically infected cemented stems; (2) success in treating late-onset acute infections in well-ingrown cementless stems; and (3) what complications were associated with this approach in a small case series.', "Between January 2002 and July 2013, 30 patients (30 hips) presented to the senior author for treatment of infected THA. Of those, 21 patients (21 hips) with infected cemented THAs underwent débridement and single-stage revision to cementless total hip implants followed by catheter infusion of intraarticular antibiotics. Nine patients (nine hips) with late-onset acute infections in cementless THA had bone-ingrown implants. These patients were all more than 2 years from their original surgery and had acute symptoms of infection for 4 to 9 days. Seven had their original THA elsewhere, and two were the author's patients. All were symptom-free until the onset of their infection, and none had postoperative wound complications, fever, or prolonged pain suggestive of a more chronic process. They were treated with débridement and head and liner exchange, again followed by catheter infusion of intraarticular antibiotics. During this time period, this represented all infected THAs treated by the senior author, and all were treated with this protocol; no patient underwent two-stage exchange during this time, and no patients were lost to followup. At the time of the surgery, two Hickman catheters were placed in each hip to begin intraarticular delivery of antibiotics in the early postoperative period. Antibiotics were infused daily into the hip for 6 weeks with the tubes used for infusion only. Eleven of the single-stage revisions and four of the hips treated with débridement had methicillin-resistant Staphylococcus aureus. Patients were considered free of infection if they had no clinical signs of infection and had a normal C-reactive protein and erythrocyte sedimentation rate at 1 year. Complications were ascertained by chart review.", 'Twenty of 21 (95%) infections in patients who had single-stage revision for chronically infected cemented THA were apparently free from infection and remained so at a mean followup of 63 months (range, 25-157 months). One case grew Candida albicans in the operative cultures and remained free of signs of infection after rerevision followed by infusion of fluconazole. The nine cementless THAs treated with débridement and head/liner exchange all remained free of signs of infection at a mean followup of 74 months (range, 62-121 months). Few complications were associated with the technique. Four patients had elevated serum levels of vancomycin without renal function changes and two patients had transient blood urea nitrogen/creatinine elevations with normal vancomycin levels that resolved with dosage adjustments. No patient had evidence of permanent renal damage. None of the patients in this study developed a chronic fistula or had significant drainage from the catheter site.\Question: Does one-stage Revision With Catheter Infusion of Intraarticular Antibiotics Successfully treat Infected THA?

Ex Output:

Single-stage revision for chronically infected cemented THA and débridement of bone-ingrown cementless THA with late-onset acute infection followed with indwelling catheter antibiotic infusion can result in infection eradication even when resistant organisms are involved. Larger study groups would better assess this technique and prospective comparisons to more traditional one- and two-stage revision techniques for infected THA will likely require multi-institutional approaches.


