Removing noise from pyrosequenced amplicons

Background In many environmental genomics applications a homologous region of DNA from a diverse sample is first amplified by PCR and then sequenced. The next generation sequencing technology, 454 pyrosequencing, has allowed much larger read numbers from PCR amplicons than ever before. This has revolutionised the study of microbial diversity as it is now possible to sequence a substantial fraction of the 16S rRNA genes in a community. However, there is a growing realisation that because of the large read numbers and the lack of consensus sequences it is vital to distinguish noise from true sequence diversity in this data. Otherwise this leads to inflated estimates of the number of types or operational taxonomic units (OTUs) present. Three sources of error are important: sequencing error, PCR single base substitutions and PCR chimeras. We present AmpliconNoise, a development of the PyroNoise algorithm that is capable of separately removing 454 sequencing errors and PCR single base errors. We also introduce a novel chimera removal program, Perseus, that exploits the sequence abundances associated with pyrosequencing data. We use data sets where samples of known diversity have been amplified and sequenced to quantify the effect of each of the sources of error on OTU inflation and to validate these algorithms

Implemented Interventions at the Naef K. Basile Cancer Institute to Protect Patients and Medical Personnel From COVID Infections: Effectiveness and Patient Satisfaction

BackgroundThe Coronavirus Disease 2019 (COVID-19) was declared a pandemic by WHO in March 2020. The first case of COVID-19 was identified in Lebanon on the 21st of February 2020, amid a national economic crisis. As the numbers of cases increased, ICU admissions and mortality rose, which led hospitals across Lebanon to take certain safety measures to contain the virus. The Naef K. Basile Cancer Institute (NKBCI) at the American University of Beirut Medical Center handles oncology outpatient visits and outpatient treatment protocol infusions. The aim of this study is to evaluate the efficacy of the safety measures put forth by the NKBCI early in the pandemic.MethodsOncology patients are amongst the immunosuppressed population, who are at greatest risk of contracting COVID-19 and consequently suffering its complications. In this manuscript, we evaluated the precautionary measures implemented at the NKBCI of AUBMC from March 1st to May 31st of 2020, by surveying oncology patients on the telephone who had live and virtual appointments in both the oncology outpatient clinics and infusion unit. We conducted a prospective study of 670 oncology patients who had appointments at the NKBCI during this period and used their answers to draw responses about patient satisfaction towards those safety measures.ResultsOur results involved 387 responses of oncology patients who visited the NKBCI during the period of March 1st to May 31st of 2020. 99% of our respondents gave a rating of good to excellent with these new measures. The option of online consultation was given to 35% in the hematology group compared to 19% in those with solid tumors (p=0.001). From the total, 15% of patients opted for the telemedicine experience as a new implemented strategy to provide patient-centered medical care. Of this group of patients, 22% faced problems with connectivity and 19% faced problems with online payment.ConclusionNKBCI was competent in following the WHO guidelines in protecting the oncology patient population. Feedback collected from the surveys will be taken into account by the committee of the NKBCI to develop new safety measures that can better control viral spread while providing patient-centered medical care

Unilateral anterior uveitis complicating zoledronic acid therapy in breast cancer

BACKGROUND: Zoledronic acid is very widely used in patients with metastatic bone disease and osteoporosis. Only one case of bilateral uveitis was recently reported related to its use. CASE PRESENTATION: We report the first case of severe unilateral anterior uveitis in a patient with breast cancer and an intraocular lens. Following zoledronic acid infusion, the patient developed severe and dramatic right eye pain with decreased visual acuity within 24 hours and was found to have a fibrinous anterior uveitis of moderate severity The patient was treated with topical prednisone and atropine eyedrops and recovered slowly over several months. CONCLUSION: Internists, oncologists, endocrinologists, and ophtalmologists should be aware of uveitis as a possible complication of zoledronic acid therapy. Patients should be instructed to report immediately to their physicians and treatment with topical prednisone and atropine eyedrops should be instituted immediately at the onset of symptoms. This report documents anterior uveitis as a complication of zoledronic acid therapy. This reaction could be an idiosyncratic one but further research may shed more light on the etiology

The future of systemic treatment of breast cancer

info:eu-repo/semantics/publishe

Vitamin D and Its Potential Interplay With Pain Signaling Pathways

About 50 million of the U.S. adult population suffer from chronic pain. It is a complex disease in its own right for which currently available analgesics have been deemed woefully inadequate since ~20% of the sufferers derive no benefit. Vitamin D, known for its role in calcium homeostasis and bone metabolism, is thought to be of clinical benefit in treating chronic pain without the side-effects of currently available analgesics. A strong correlation between hypovitaminosis D and incidence of bone pain is known. However, the potential underlying mechanisms by which vitamin D might exert its analgesic effects are poorly understood. In this review, we discuss pathways involved in pain sensing and processing primarily at the level of dorsal root ganglion (DRG) neurons and the potential interplay between vitamin D, its receptor (VDR) and known specific pain signaling pathways including nerve growth factor (NGF), glial-derived neurotrophic factor (GDNF), epidermal growth factor receptor (EGFR), and opioid receptors. We also discuss how vitamin D/VDR might influence immune cells and pain sensitization as well as review the increasingly important topic of vitamin D toxicity. Further and experimental studies will be required to study these potential interactions specifically in pain models. Such studies could highlight the potential usefulness of vitamin D either alone or in combination with existing analgesics to better treat chronic pain

Angiogenesis and cancer: A cross-talk between basic science and clinical trials (the "do ut des" paradigm).

Angiogenesis plays a crucial role in facilitating tumor growth and the metastatic process, and it is the result of a dynamic balance between pro-angiogenic factors, like vascular endothelial growth factor (VEGF) and platelet-derived growth factor, and antiangiogenic factors, like thrombospondin-1 and angiostatin. Many drugs that target human tumors, like bevacizumab and some VEGF-receptor tyrosine-kinase inhibitors (e.g. BAY 43-9006, SU11248 and PTK787/ZK222584) have been studied in clinical trials, with favorable toxicity reports and encouraging results in advanced colorectal cancer, renal cell cancer, breast cancer and non-squamous non-small cell lung cancer, either combined with chemotherapy, or in monotherapy. Another potential approach to inhibiting angiogenesis is through metronomic chemotherapy (low doses of chemotherapy for long periods of time). This review describes the mechanisms of the angiogenic process and evaluates the recent data about antiangiogenic therapies in clinical trials.Journal ArticleResearch Support, Non-U.S. Gov'tReviewinfo:eu-repo/semantics/publishe