FinaleToolkit: Accelerating Cell-Free DNA Fragmentation Analysis with a High-Speed Computational Toolkit.

Cell-free DNA (cfDNA) fragmentation pattern represents a promising non-invasive biomarker for disease diagnosis and prognosis. Numerous fragmentation features, such as end motif and window protection score (WPS), have been characterized in cfDNA genomic sequencing. However, the analytical tools developed in these studies are often not released to the liquid biopsy community or are inefficient for genome-wide analysis in large datasets. To address this gap, we have developed FinaleToolkit, a fast and memory efficient Python package designed to generate comprehensive fragmentation features from large cfDNA genomic sequencing data. For instance, FinaleToolkit can generate genome-wide WPS features from a ~100X cfDNA whole-genome sequencing (WGS) dataset in 1.2 hours using 16 CPU cores, offering up to a ~50-fold increase in processing speed compared to original implementations in the same dataset. We have benchmarked FinaleToolkit against original studies or implementations where possible, confirming its efficacy. Furthermore, FinaleToolkit enabled the genome-wide analysis of fragmentation patterns over arbitrary genomic intervals, significantly boosting the performance for cancer early detection. FinaleToolkit is open source and thoroughly documented with both command line interface and Python application programming interface (API) to facilitate its widespread adoption and use within the research community: https://github.com/epifluidlab/FinaleToolkit.

Lessons of the month 1: When what you see is not UC (ulcerative colitis): an unusual presentation of pancolitis in a developed country.

The misdiagnosis of intestinal schistosomiasis is not uncommon given its variety of clinical manifestations and often shares similarities with ulcerative colitis. While endoscopy aids in diagnosis, findings are often non-specific and correlation with histopathological features is crucial in arriving at an accurate diagnosis which is confirmed by the presence of schistosome ova within the lamina propria. In this case study, we report our experience with a 50-year-old woman, who had been residing in Singapore for more than a decade, presenting with recurrent episodes of bloody diarrhoea.

Lessons of the month 2: Ocular manifestations and complications of hepatitis C infection.

We present a case of a man with hepatitis C with acute visual loss in his left eye over a 3-day period. Initial evaluation suggested a possible idiopathic orbital inflammatory syndrome as underlying cause for his symptoms. Initial response to systemic glucocorticoids and antiviral treatment were encouraging with improvement in the patient's visual acuity. After a period of loss to follow up and discontinuation of treatment, the patient re-presented with visual loss in his left eye. Re-evaluation confirmed a diagnosis of marginal zone B-cell lymphoma. This case illustrates the importance of considering the various ocular manifestations of hepatitis C.

Management of Percutaneous Endoscopic Gastrostomy Site Gastric Ulcer in a Patient with an Esophageal Stricture and Hiatus Hernia.

Percutaneous endoscopic gastrostomy (PEG) is commonly performed for feeding difficulties, in patients suffering from complications of nasopharyngeal carcinoma and its treatment, namely radiotherapy and surgery. This case report describes the challenges in hemostasis and subsequent re-establishment of enteral access for feeding, in an elderly patient with a history of NPC, treated surgically, followed by radiotherapy, who presented with massive hematemesis following reinsertion of her PEG shortly after an accidental dislodgement. Her previous nasopharyngectomy, wide field radiation therapy, and radical neck dissection precluded nasogastric tube feeding, and the presence of a large hiatus hernia made reinsertion of a new PEG technically challenging. This case highlights the methods used to overcome the above challenges.