Inosine monophosphate dehydrogenase 2 (IMPDH2) modulates response to therapy and chemo-resistance in triple negative breast cancer.

Triple negative breast cancer (TNBC) is one of the deadliest subtypes of breast cancer, whose high frequency of relapse is often due to resistance to chemotherapy. Here, we identify inosine monophosphate dehydrogenase 2 (IMPDH2) as a contributor to doxorubicin resistance, in multiple TNBC models. Analysis of publicly available datasets reveals elevated IMPDH2 expression to associate with worse overall TNBC prognosis in the clinic, including lower recurrence-free survival post adjuvant/neoadjuvant therapy.

Clinical decision making in prostate cancer care-evaluation of EAU-guidelines use and novel decision support software.

Keeping up to date with the latest clinical advances in prostate cancer can be challenging. We investigated the impact of guideline use on quality of treatment decisions as well as the impact of a novel, CE-certified clinical decision support tool (Siemens AIPC software) on the amount of time clinicians spend on decision-making in a multicenter setting. Ten urologists assessed ten clinical cases (screening and localized prostate cancer) in three settings: without support, using a digital version of the EAU guidelines, and with the AIPC tool, resulting in 300 clinical decisions.

Initial experience with AI Pathway Companion: Evaluation of dashboard-enhanced clinical decision making in prostate cancer screening.

Purpose: Rising complexity of patients and the consideration of heterogeneous information from various IT systems challenge the decision-making process of urological oncologists. Siemens AI Pathway Companion is a decision support tool that provides physicians with comprehensive patient information from various systems. In the present study, we examined the impact of providing organized patient information in comprehensive dashboards on information quality, effectiveness, and satisfaction of physicians in the clinical decision-making process.

Somatic Features of Response and Relapse in Non-muscle-invasive Bladder Cancer Treated with Bacillus Calmette-Guérin Immunotherapy.

Background: High-risk non-muscle-invasive bladder cancer (NMIBC) is treated with bacillus Calmette-Guérin (BCG), but relapse is common. Improvement of patient outcomes requires better understanding of links between BCG resistance and genomic driver alterations.

Objective: To validate the prognostic impact of common genomic alterations in NMIBC pretreatment and define somatic changes present in post-BCG relapses.

Toward a Platform for Structured Data Acquisition in Oncology: A Pilot Study on Prostate Cancer Screening.

Introduction: Physicians spend an ever-rising amount of time to collect relevant information from highly variable medical reports and integrate them into the patient's health condition.

Objectives: We compared synoptic reporting based on data elements to narrative reporting in order to evaluate its capabilities to collect and integrate clinical information.

Methods: We developed a novel system to align medical reporting to data integration requirements and tested it in prostate cancer screening.

Novices in MRI-targeted prostate biopsy benefit from structured reporting of MRI findings.

Purpose: The aim of this study was to investigate whether structured reports (SRs) of prostate MRI results are more suitable than non-structured reports (NSRs) for promoting the more accurate assessment of the location of a single prostate cancer lesion by novices in MRI-targeted biopsy.

Methods: 50 NSRs and 50 SRs describing a single prostatic lesion were presented to 5 novices in MRI-targeted biopsy. The participants were asked to plot the tumor location in a two-dimensional prostate diagram and to answer a questionnaire on the quality of the reports.

Immunocytochemistry for ARID1A as a potential biomarker in urine cytology of bladder cancer.

Background: Mutations of AT-rich interactive domain 1 (ARID1A) have been associated with a worse outcome after intravesical treatment with bacille Calmette-Guérin in patients with non-muscle-invasive bladder cancer (NMIBC). Loss of ARID1A protein expression in urine cytology may serve as an indication of an ARID1A mutation. Therefore, the authors examined the expression of ARID1A in urine cytology and histological specimens of bladder cancer for correlation with ARID1A mutational status.

Pitfalls in the triage and evaluation of patients with suspected acute ethanol intoxication in an emergency department.

Acute ethanol intoxication (AEI) is frequent in emergency departments (EDs). These patients are at risk of mistriage, and to leave the ED without being seen. This study's objective was to describe the process and performance of triage and trajectory for patients with suspected AEI.

Building on a Solid Foundation: Enhancing Bacillus Calmette-Guérin Therapy.

Context: More than 40 yr ago, bacillus Calmette-Guérin (BCG) was introduced as an adjuvant therapy following transurethral resection of papillary tumours and as a treatment for carcinoma in situ of the bladder. Some 30 yr after its introduction, BCG maintenance therapy was found to be superior to induction therapy alone, representing the most relevant clinical improvement to BCG therapy since its inception.

Objective: To review current efforts and future opportunities to improve BCG immunotherapy.

Profound hyponatraemia in the emergency department: seasonality and risk factors.

Aims Of The Study: Profound hyponatremia (<125 mmol/l) is frequent in the emergency department. Its incidence appears to increase during hot weather. Our objectives were to investigate seasonal variations in the incidence of profound hyponatraemia and identify its risk factors.

Diffuse leptomeningeal histiocytic sarcoma in the cerebrospinal fluid of 2 dogs.

Two adult male castrated dogs were evaluated for progressive paraparesis and ataxia. Neurologic examination showed severe ataxia, delayed proprioceptive placement in the pelvic limbs, pain upon palpation of the lumbar spine as well as facial paresis in one dog, and decreased withdrawal reflex of the pelvic limbs in the other dog. Magnetic resonance imaging (MRI) in both dogs showed diffuse meningeal and intramedullary lesions.

An architecture for adaptive algorithmic hybrids.

We describe a cognitive architecture for creating more robust intelligent systems. Our approach is to enable hybrids of algorithms based on different computational formalisms to be executed. The architecture is motivated by some features of human cognitive architecture and the following beliefs: 1) Most existing computational methods often exhibit some of the characteristics desired of intelligent systems at the cost of other desired characteristics and 2) a system exhibiting robust intelligence can be designed by implementing hybrids of these computational methods.

Appropriate training and retention of community doctors in rural areas: a case study from Mali.

Background: While attraction of doctors to rural settings is increasing in Mali, there is concern for their retention. An orientation course for young practicing rural doctors was set up in 2003 by a professional association and a NGO. The underlying assumption was that rurally relevant training would strengthen doctors' competences and self-confidence, improve job satisfaction, and consequently contribute to retention.

TFIIIC binding sites function as both heterochromatin barriers and chromatin insulators in Saccharomyces cerevisiae.

Chromosomal sites of RNA polymerase III (Pol III) transcription have been demonstrated to have "extratranscriptional" functions, as the assembled Pol III complex can act as chromatin boundaries or pause sites for replication forks, can alter nucleosome positioning or affect transcription of neighboring genes, and can play a role in sister chromatid cohesion. Several studies have demonstrated that assembled Pol III complexes block the propagation of heterochromatin-mediated gene repression. Here we show that in Saccharomyces cerevisiae tRNA genes (tDNAs) and even partially assembled Pol III complexes containing only the transcription factor TFIIIC can exhibit chromatin boundary functions both as heterochromatin barriers and as insulators to gene activation.

[Neighbourhood rural medicine: an experience of rural doctors in Mali].

The main constraint to improving access to health services of quality in rural areas is to attract qualified health personnel in these areas. A fifteen years experience in rural health in Mali has shown that it is possible to develop community medicine practices in an African context that do integrate individual care and public health activities. The policy of decentralization of health services encouraged local communities and municipalities to recruit rural doctors themselves.

North-South exchange and professional development: experience from Mali and France.

Background: Developing countries are facing the challenge of developing a family practice culture in a context in which clinical practice remains strongly associated with hospital practice. To what extent can professional exchange between GPs from North and South fuel novel professional identities in family practice?

Objectives: Assess to what extent a North-South professional exchange programme involving rural GPs from Mali and France affected practice development and professional identity formation of Malian GPs.

Methods: Qualitative analysis of 19 exchanges between rural GPs from Mali and France based on (i) interviews; (ii) retrospective report analysis; (iii) field observation of three exchanges; (iv) workshop with Malian GPs; and (v) workshop with French GPs.

Requirement of Nhp6 proteins for transcription of a subset of tRNA genes and heterochromatin barrier function in Saccharomyces cerevisiae.

A key event in tRNA gene (tDNA) transcription by RNA polymerase (Pol) III is the TFIIIC-dependent assembly of TFIIIB upstream of the transcription start site. Different tDNA upstream sequences bind TFIIIB with different affinities, thereby modulating tDNA transcription. We found that in the absence of Nhp6 proteins, the influence of the 5'-flanking region on tRNA gene transcription is dramatically enhanced in Saccharomyces cerevisiae.

Interface flow process audit: using the patient's career as a tracer of quality of care and of system organisation.

Objectives: This case study aims to demonstrate the method's feasibility and capacity to improve quality of care. Several drawbacks attached to tracer condition and selected procedure audits oblige clinicians to rely on external evaluators. Interface flow process audit is an alternative method, which also favours integration of health care across institutions divide.

Enumeration and characterization of culturable arsenate resistant bacteria in a large estuary.

Arsenic is a toxic element that exists in two major inorganic forms, arsenate and arsenite. A number of bacteria have been shown to resist arsenic exposure, and even more bacteria appear to possess the genes for arsenic resistance. In this study, the numbers of culturable arsenate-resistant bacteria present in water at three coastal sites in the Lake Pontchartrain estuary, Louisiana, was determined.

Phylogenetic analysis of bacterial and archaeal arsC gene sequences suggests an ancient, common origin for arsenate reductase.

Background: The ars gene system provides arsenic resistance for a variety of microorganisms and can be chromosomal or plasmid-borne. The arsC gene, which codes for an arsenate reductase is essential for arsenate resistance and transforms arsenate into arsenite, which is extruded from the cell. A survey of GenBank shows that arsC appears to be phylogenetically widespread both in organisms with known arsenic resistance and those organisms that have been sequenced as part of whole genome projects.

A postmarketing surveillance evaluation of quinapril in 3742 Canadian hypertensive patients: the ACCEPT Study. Accupril Canadian Clinical Evaluation and Patient Teaching.

The Accupril Canadian Clinical Evaluation and Patient Teaching (ACCEPT) study was a multicenter, 6-month, open-label, postmarketing surveillance study where the efficacy and safety of quinapril, an angiotensin-converting enzyme (ACE) inhibitor, was evaluated in a general population of patients with essential hypertension. Participating physicians followed their normal office procedures for the initiation of quinapril therapy (a dose of 10 mg QD in the majority of cases). The dose was titrated to blood pressure response, generally at 2-week intervals, for a maintenance dose of 10 mg QD to 20 mg QD in most cases (86% at 6 months) and not to exceed 40 mg QD.