Age distribution of retinoblastoma tumours in familial disease.

Background: 40% of children with retinoblastoma have an RB1 gene mutation identified, known as heritable retinoblastoma. It is important to undertake active surveillance (screening) of relatives of those with identified RB1 gene mutations and ensure ongoing surveillance to monitor for new tumour formation or recurrences. Current guidance is to screen patients up to the age of 7 years old.

The Impact of Mind-Body Medicine on Patient-Reported Outcomes in the Management of Chronic Pelvic Pain.

Background Recent research has suggested a role for mindfulness-based therapy for patients with chronic medical conditions, but there is limited data on pelvic pain. We aim to determine if mindfulness improves patient-reported outcomes in pelvic pain and to determine the feasibility of implementation of this program. Methodology This is a pilot feasibility trial consisting of women with chronic pelvic pain at a single academic tertiary referral clinic.

Global research alliance in infectious disease: a collaborative effort to combat infectious diseases through dissemination of portable sequencing.

Objective: To disseminate the portable sequencer MinION in developing countries for the main purpose of battling infectious diseases, we found a consortium called Global Research Alliance in Infectious Diseases (GRAID). By holding and inviting researchers both from developed and developing countries, we aim to train the participants with MinION's operations and foster a collaboration in infectious diseases researches. As a real-life example in which resources are limited, we describe here a result from a training course, a metagenomics analysis from two blood samples collected from a routine cattle surveillance in Kulan Progo District, Yogyakarta Province, Indonesia in 2019.

Hemosiderin deposition evaluation in hemophilic ankle joints: association between US finding and gradient-recalled echo MR imaging sequence.

Background: Repeated bleeding in hemophilic arthropathy (HA) may result in severe degenerative changes and joint destruction. The gradient-recalled echo (GRE) sequence MR is proved to be the best method to detect hemosiderin deposition. However, MR is not widely available in developing countries, including Indonesia.

Impact of long-term ibrutinib treatment on circulating immune cells in previously untreated chronic lymphocytic leukemia.

This study evaluated long-term immunophenotypic changes in circulating levels of 24 immune cell subsets through 4 years of continuous treatment with first-line ibrutinib (420 mg once daily) in 31 patients with chronic lymphocytic leukemia (CLL) from the RESONATE-2 study, and compared them with untreated age-matched healthy donors (n = 20). Ibrutinib progressively decreased total B-cell counts and preferentially targeted malignant CLL B cells over normal B cells. Elevated counts of chronically activated, exhausted, and effector memory T cells were normalized within 6-16 months, while naive T cells remained mostly within healthy donor range (HDR).

Ibrutinib restores immune cell numbers and function in first-line and relapsed/refractory chronic lymphocytic leukemia.

Ibrutinib positively modulates many T-cell subsets in chronic lymphocytic leukemia (CLL). To understand ibrutinib's effects on the broader landscape of immune cell populations, we comprehensively characterized changes in circulating counts of 21 immune blood cell subsets throughout the first year of treatment in patients with relapsed/refractory (R/R) CLL (n = 55, RESONATE) and previously untreated CLL (n = 50, RESONATE-2) compared with untreated age-matched healthy donors (n = 20). Ibrutinib normalized abnormal immune cell counts to levels similar to those of age-matched healthy donors.

Relative Selectivity of Covalent Inhibitors Requires Assessment of Inactivation Kinetics and Cellular Occupancy: A Case Study of Ibrutinib and Acalabrutinib.

Kinases form an attractive class of targets for small molecule inhibitors, but similarity among their adenosine triphosphate binding sites presents difficulties for developing selective drugs. Standard methods of evaluating selectivity of most reversibly bound drugs account for binding affinity but not the two-step process, affinity and inactivation, occurring during covalent inhibition. To illustrate this concept, we assessed the selectivity of Bruton's tyrosine kinase (BTK) over TEC kinases by two novel therapeutics: ibrutinib and acalabrutinib.

Portable sequencer in the fight against infectious disease.

Infectious disease is still a major threat in the world today. Five decades ago, it was considered soon to be eradicated, but the adaptation of pathogens to environmental pressure, such as antimicrobials, encouraged the emergence and reemergence of infectious disease. The fight with infectious disease starts with prevention, diagnosis, and treatment.

Visceral Adipose Tissue Modulates Radiosensitivity in Oesophageal Adenocarcinoma.

Oesophageal adenocarcinoma (OAC) is an exemplar model of obesity-associated cancer. Response to neoadjuvant chemoradiotherapy (NA CRT) is a clinical challenge. We examined if visceral adipose tissue and obesity status alter radiosensitivity in OAC.

On-Site MinION Sequencing.

DNA sequencing has reached an unprecedented level with the advent of Oxford Nanopore Technologies' MinION. The low equipment investment, ease of library preparation, small size, and powered only by a laptop computer enable the portability for on-site sequencing. MinION has had its role in clinical, biosecurity, and environmental fields.

Nanopore sequencing of drug-resistance-associated genes in malaria parasites, Plasmodium falciparum.

Here, we report the application of a portable sequencer, MinION, for genotyping the malaria parasite Plasmodium falciparum. In the present study, an amplicon mixture of nine representative genes causing resistance to anti-malaria drugs is diagnosed. First, we developed the procedure for four laboratory strains (3D7, Dd2, 7G8, and K1), and then applied the developed procedure to ten clinical samples.

Aflibercept in Diabetic Macular Oedema Previously Refractory to Standard Intravitreal Therapy: An Irish Retrospective Study.

Introduction: To determine visual and anatomical outcomes of diabetic macular oedema (DMO) patients in a tertiary centre following conversion to aflibercept having been refractory to previous treatment with bevacizumab/ranibizumab.

Methods: A retrospective case series of patients with a diagnosis of DMO undergoing aflibercept intravitreal therapy for at least 6 months who had previous treatment with three consecutive bevacizumab/ranibizumab injections pre-switch. Exclusion criteria included other procedures affecting visual outcome performed within the treatment period.

Changing trends in postoperative cataract care: impact of electronic patient records in optometrist-delivered shared care.

Background: This study evaluates a community optometrist-delivered postoperative care scheme in patients discharged from the hospital ophthalmology department following uncomplicated cataract surgery.

Aim: The aim of this study is to assess the efficacy of electronic patient records (EPR) in facilitating co-managed cataract care.

Methods: We performed a retrospective analysis of a prospectively maintained Medisoft EPR database of postoperative cataract review data at a single centre, Sligo University Hospital (SUH), which serves a large and predominantly rural catchment area.

Serotyping dengue virus with isothermal amplification and a portable sequencer.

The recent development of a nanopore-type portable DNA sequencer has changed the way we think about DNA sequencing. We can perform sequencing directly in the field, where we collect the samples. Here, we report the development of a novel method to detect and genotype tropical disease pathogens, using dengue fever as a model.

Impact of visceral obesity and metabolic syndrome on the postoperative immune, inflammatory, and endocrine response following surgery for esophageal adenocarcinoma.

Visceral obesity and metabolic syndrome (MetSyn) represent a constellation of inflammation, insulin resistance, and hyperglycemia and are established risk factors for gastrointestinal cancer. However, their impact on the immune and inflammatory response after major upper gastrointestinal oncologic surgery is unknown. In 125 consecutive patients who underwent esophagectomy, C-reactive protein (CRP) and CRP:albumin levels were recorded preoperatively and on days 1, 3, 7, and 14 postoperatively.

Genetic polymorphisms in Plasmodium falciparum chloroquine resistance genes, pfcrt and pfmdr1, in North Sulawesi, Indonesia.

Background: Malaria still poses one of the major threats to human health. Development of effective antimalarial drugs has decreased this threat; however, the emergence of drug-resistant Plasmodium falciparum, a cause of Malaria, is disconcerting. The antimalarial drug chloroquine has been effectively used, but resistant parasites have spread worldwide.

Parallel Profiles of Inflammatory and Effector Memory T Cells in Visceral Fat and Liver of Obesity-Associated Cancer Patients.

In the midst of a worsening obesity epidemic, the incidence of obesity-associated morbidities, including cancer, diabetes, cardiac and liver disease is increasing. Insights into mechanisms underlying pathological obesity-associated inflammation are lacking. Both the omentum, the principal component of visceral fat, and liver of obese individuals are sites of excessive inflammation, but to date the T cell profiles of both compartments have not been assessed or compared in a patient cohort with obesity-associated disease.

Low miR-187 expression promotes resistance to chemoradiation therapy in vitro and correlates with treatment failure in patients with esophageal adenocarcinoma.

Esophageal adenocarcinoma (EAC) has a poor prognosis and is increasing in incidence in many western populations. Neoadjuvant chemoradiation therapy (CRT) followed by surgery is increasingly the standard of care for locally advanced EAC; however, resistance to treatment is a significant clinical problem. The identification of both novel biomarkers predicting response to treatment and novel therapeutic targets to enhance the efficacy of CRT are key to improving survival rates in EAC.

CCR1 antagonism attenuates T cell trafficking to omentum and liver in obesity-associated cancer.

Obesity is a global health problem presenting serious risk of disease fuelled by chronic inflammation, including type 2 diabetes mellitus, cardiovascular disease, liver disease and cancer. Visceral fat, in particular the omentum and liver of obese individuals are sites of excessive inflammation. We propose that chemokine-mediated trafficking of pro-inflammatory cells to the omentum and liver contributes to local and subsequent systemic inflammation.

Visceral obesity stimulates anaphase bridge formation and spindle assembly checkpoint dysregulation in radioresistant oesophageal adenocarcinoma.

Purpose: Oesophageal adenocarcinoma is an exemplar model of obesity-associated cancer. Locally advanced disease is treated with neoadjuvant chemoradiotherapy, and survival rates are highest in patients demonstrating a pathological response following neoadjuvant therapy. Given that 55 % of oesophageal adenocarcinoma patients are obese, uncovering the effect of adipose tissue on radioresponse is clinically relevant.

Excess visceral adiposity induces alterations in mitochondrial function and energy metabolism in esophageal adenocarcinoma.

Background: Visceral obesity has a strong association with both the incidence and mortality of esophageal adenocarcinoma (EAC). Alterations in mitochondrial function and energy metabolism is an emerging hallmark of cancer, however, the potential role that obesity plays in driving these alterations in EAC is currently unknown.

Methods: Adipose conditioned media (ACM) was prepared from visceral adipose tissue taken from computed tomography-determined viscerally-obese and non-obese EAC patients.

DB-AT: a 2015 update to the Full-parasites database brings a multitude of new transcriptomic data for apicomplexan parasites.

The previous release of our Full-parasites database (http://fullmal.hgc.jp/) brought enhanced functionality, an expanded full-length cDNA content, and new RNA-Seq datasets from several important apicomplexan parasites.

Interactive transcriptome analysis of malaria patients and infecting Plasmodium falciparum.

To understand the molecular mechanisms of parasitism in vivo, it is essential to elucidate how the transcriptomes of the human hosts and the infecting parasites affect one another. Here we report the RNA-seq analysis of 116 Indonesian patients infected with the malaria parasite Plasmodium falciparum (Pf). We extracted RNAs from their peripheral blood as a mixture of host and parasite transcripts and mapped the RNA-seq tags to the human and Pf reference genomes to separate the respective tags.