mapMECFS: a portal to enhance data discovery across biological disciplines and collaborative sites.

BACKGROUND: Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a debilitating disease which involves multiple body systems (e.g., immune, nervous, digestive, circulatory) and research domains (e.g., immunology, metabolomics, the gut microbiome, genomics, neurology). Despite several decades of research, there are no established ME/CFS biomarkers available to diagnose and treat ME/CFS. Sharing data and integrating findings across these domains is essential to advance understanding of this complex disease by revealing diagnostic biomarkers and facilitating discovery of novel effective therapies. METHODS: The National Institutes of Health funded the development of a data sharing portal to support collaborative efforts among an initial group of three funded research centers. This was subsequently expanded to include the global ME/CFS research community. Using the open-source comprehensive knowledge archive network (CKAN) framework as the base, the ME/CFS Data Management and Coordinating Center developed an online portal with metadata collection, smart search capabilities, and domain-agnostic data integration to support data findability and reusability while reducing the barriers to sustainable data sharing. RESULTS: We designed the mapMECFS data portal to facilitate data sharing and integration by allowing ME/CFS researchers to browse, share, compare, and download molecular datasets from within one data repository. At the time of publication, mapMECFS contains data curated from public data repositories, peer-reviewed publications, and current ME/CFS Research Network members. CONCLUSIONS: mapMECFS is a disease-specific data portal to improve data sharing and collaboration among ME/CFS researchers around the world. mapMECFS is accessible to the broader research community with registration. Further development is ongoing to include novel systems biology and data integration methods.

'I've got a little list'-the scourge of a surgical junior. A quality improvement project to change the surgical patient list in a district general hospital.

BACKGROUND: Junior doctors at the Royal Devon and Exeter Hospital spend hours every day creating and updating patient lists for all surgical specialties on Microsoft Excel spreadsheets. This not only consumes time that should be spent on clinical tasks, it allows for human errors, system errors and patient safety concerns. Our aim was to reduce time spent on the list and reduce the chance for error. METHODS: We measured the time junior doctors spent creating and updating the surgical lists for one specialty, and on-call shifts. Our first Plan-Do-Study-Act (PDSA) cycle was to introduce clinical secretaries; this reduced the time spent by ward teams on the list but had no effect on the on-call team. We then worked with the hospital application developer to adapt software currently used to suit all surgical teams. Once completed, this software was rolled out alongside the existing spreadsheet method with a view to a switch after a transition period. RESULTS: The introduction of clinical secretaries reduced the time spent on the colorectal surgery list from 99.22 min a day to 43.38 min. The on-call team however did not benefit from this intervention. Following the introduction of the new software, the day on-call team time spent on the list changed from 121 min a day to 4.66 min. The night on-call team time changed from 91 min to 7.38 min. CONCLUSION: Reducing the time juniors spend compiling surgical lists has clear benefits to patients with extra time for junior doctors to clerk patients. The use of an automated system removes the chance of error in transcription of blood results. Due to the success of this project, colorectal, upper gastrointestinal, urology, vascular and on-call teams have adopted the new list permanently.

The growth of methylammonium lead iodide perovskites by close space vapor transport.

Vapor deposition processes have shown promise for high-quality perovskite solar cells with potential pathways for scale-up to large area manufacturing. Here, we present a sequential close space vapor transport process to deposit CH3NH3PbI3 (MAPI) perovskite thin films by depositing a layer of PbI2 then reacting it with CH3NH3I (MAI) vapor. We find that, at T = 100 °C and pressure = 9 torr, a ∼225 nm-thick PbI2 film requires ≥125 minutes in MAI vapor to form a fully-reacted MAPI film. Raising the temperature to 160 °C increases the rate of reaction, such that MAPI forms within 15 minutes, but with reduced surface coverage. The reaction kinetics can be approximated as roughly first-order with respect to PbI2, though there is evidence for a more complicated functional relation. Perovskite films reacted at 100 °C for 150 minutes were fabricated into solar cells with an SLG/ITO/CdS/MAPI/Spiro-OMeTAD/Au structure, and a device efficiency of 12.1% was achieved. These results validate the close space vapor transport process and serve as an advance toward scaled-up, vapor-phase perovskite manufacturing through continuous vapor transport deposition.

Transdermal optogenetic peripheral nerve stimulation.

OBJECTIVE: A fundamental limitation in both the scientific utility and clinical translation of peripheral nerve optogenetic technologies is the optical inaccessibility of the target nerve due to the significant scattering and absorption of light in biological tissues. To date, illuminating deep nerve targets has required implantable optical sources, including fiber-optic and LED-based systems, both of which have significant drawbacks. APPROACH: Here we report an alternative approach involving transdermal illumination. Utilizing an intramuscular injection of ultra-high concentration AAV6-hSyn-ChR2-EYFP in rats. MAIN RESULTS: We demonstrate transdermal stimulation of motor nerves at 4.4 mm and 1.9 mm depth with an incident laser power of 160 mW and 10 mW, respectively. Furthermore, we employ this technique to accurately control ankle position by modulating laser power or position on the skin surface. SIGNIFICANCE: These results have the potential to enable future scientific optogenetic studies of pathologies implicated in the peripheral nervous system for awake, freely-moving animals, as well as a basis for future clinical studies.

Evaluation of aromatic amines with different purities and different solvent vehicles in the Ames test.

Of all the in vitro mutagenicity assays, the Ames test displays the best correlation with rodent carcinogenicity and therefore carries significant weight with the food and drug regulatory bodies. Aromatic amines (AA) are ubiquitous structural groups in food and drug molecules despite the well-documented mutagenic and carcinogenic propensity for many representatives. Furthermore, recent regulatory guidelines (that is ICH M7) requires the hazard assessment of actual and potential impurities by two complementary (Q)SAR prediction methodologies if no carcinogenicity or bacterial mutagenicity data is available. One methodology should be expert-rule-based and the second should be statistics-based. Having encountered numerous reports of contradictory Ames results for members of this chemotype, we undertook systematic Ames tests on a diverse set of 14 AAs of differing purities in different solvents, and as free bases and their salts. The aim of this work was to investigate the reliability of the Ames test for this chemotype leading to the creation of a reference set of AAs for use by medicinal chemists and in silico modelling. Contrary to previous experience, which led to the investigations reported in this publication, the anticipated transformation from an Ames-positive to an Ames-negative after purification only occurred for one compound. Furthermore, this result proved inconclusive after testing as the HCl salt in DMSO and in water. The anticipated change in class from mutagen to non-mutagen, did not occur and this can be read as evidence for the reliability of the Ames test for AAs.

Using limes and synthetic psoralens to enhance solar disinfection of water (SODIS): a laboratory evaluation with norovirus, Escherichia coli, and MS2.

We investigated the use of psoralens and limes to enhance solar disinfection of water (SODIS) using an UV lamp and natural sunlight experiments. SODIS conditions were replicated using sunlight, 2 L polyethylene terephthalate (PET) bottles, and tap water with Escherichia coli, MS2 bacteriophage, and murine norovirus (MNV). Psoralens and lime acidity both interact synergistically with UV radiation to accelerate inactivation of microbes. Escherichia coli was ablated > 6.1 logs by SODIS + Lime Slurry and 5.6 logs by SODIS + Lime Juice in 30-minute solar exposures, compared with a 1.5 log reduction with SODIS alone (N = 3; P < 0.001). MS2 was inactivated > 3.9 logs by SODIS + Lime Slurry, 1.9 logs by SODIS + Lime Juice, and 1.4 logs by SODIS in 2.5-hour solar exposures (N = 3; P < 0.05). MNV was resistant to SODIS, with < 2 log reductions after 6 hours. Efficacy of SODIS against human norovirus should be investigated further.

The performance of cerebrospinal fluid treponemal-specific antibody tests in neurosyphilis: a systematic review.

BACKGROUND: No single laboratory test is both sensitive and specific to diagnose neurosyphilis. Several major clinical guidelines suggest that negative cerebrospinal fluid (CSF) treponemal-specific antibody tests rule out the diagnosis of neurosyphilis. Our aim was to systematically review the literature and describe the performance of treponemal-specific CSF antibody tests when diagnosing neurosyphilis. METHODS: Two reviewers independently assessed studies published in electronic databases, trial registries, and bibliographies for content and quality. Entry criteria included the assessment of treponemal-specific CSF tests currently used in clinical practice, and the use of standard criteria for both diagnosis and exclusion of neurosyphilis. The primary outcomes were sensitivity, specificity, and negative predictive values of treponemal-specific CSF antibody tests. RESULTS: Of 141 unique citations, 18 studies were included in the systematic review. Due to significant heterogeneity among studies, we were unable to generate pooled summary statistics. Seven different treponemal-specific tests were assessed. Of those, 13 studies evaluated the CSF FTA-ABS (fluorescent treponemal antibody-absorbed) and 9 evaluated the CSF fluorescent treponemal antibody. The performance estimates of these tests were highly variable and depended on the choice of negative and positive controls. No single test had perfect sensitivity, thus the negative predictive value was dependant on the specificity of the test and the prevalence (i.e., pretest probability) of neurosyphilis: the higher the prevalence, the lower the negative predictive value. Few studies included HIV-infected persons. CONCLUSIONS: A negative CSF-treponemal-specific antibody test may not exclude the diagnosis of neurosyphilis when the clinical suspicion for neurosyphilis is high.

The genotype distribution of the XRCC1 gene indicates a role for base excision repair in the development of therapy-related acute myeloblastic leukemia.

Polymorphisms in several DNA repair genes have been described. These polymorphisms may affect DNA repair capacity and modulate cancer susceptibility by means of gene-environment interactions. We investigated DNA repair capacity and its association with acute myeloblastic leukemia (AML). We studied polymorphisms in 3 DNA repair genes: XRCC1, XRCC3, and XPD. We also assessed the incidence of a functional polymorphism in the NQO1 gene, which is involved in protection of cells from oxidative damage. We genotyped the polymorphisms by using polymerase chain reaction-restriction fragment-length polymorphism analysis in 134 patients with de novo AML, 34 with therapy-related AML (t-AML), and 178 controls. The distributions of the XRCC3 Thr241Met and NQO1 Pro187Ser genotypes were not significantly different in patients and controls. However, the distribution of the XRCC1 Arg399Gln genotypes was significantly different when comparing the t-AML and control groups (chi(2), P =.03). The presence of at least one XRCC1 399Gln allele indicated a protective effect for the allele in controls compared with patients with t-AML (odds ratio 0.44; 95% confidence interval, 0.20-0.93). We found no interactions between the XRCC1 or XRCC3 and NQO1 genotypes. We also found no differences in the distribution of the XPD Lys751Gln or XRCC1 Arg194Trp genotypes. Our data provide evidence of a protective effect against AML in individuals with at least one copy of the variant XRCC1 399Gln allele compared with those homozygous for the common allele.