Ethyl 2-(3-acetyl-6-methyl-2-oxo-2H-pyran-4-yl­oxy)acetate

The title compound, C12H14O6, features a roughly planar mol­ecule (r.m.s. deviation for all non-H atoms = 0.287 Å). In the crystal, the mol­ecules are held together by C—H⋯O hydrogen bonds

Translating and evaluating historic phenotyping algorithms using SNOMED CT

OBJECTIVE: Patient phenotype definitions based on terminologies are required for the computational use of electronic health records. Within UK primary care research databases, such definitions have typically been represented as flat lists of Read terms, but Systematized Nomenclature of Medicine-Clinical Terms (SNOMED CT) (a widely employed international reference terminology) enables the use of relationships between concepts, which could facilitate the phenotyping process. We implemented SNOMED CT-based phenotyping approaches and investigated their performance in the CPRD Aurum primary care database. MATERIALS AND METHODS: We developed SNOMED CT phenotype definitions for 3 exemplar diseases: diabetes mellitus, asthma, and heart failure, using 3 methods: "primary" (primary concept and its descendants), "extended" (primary concept, descendants, and additional relations), and "value set" (based on text searches of term descriptions). We also derived SNOMED CT codelists in a semiautomated manner for 276 disease phenotypes used in a study of health across the lifecourse. Cohorts selected using each codelist were compared to "gold standard" manually curated Read codelists in a sample of 500 000 patients from CPRD Aurum. RESULTS: SNOMED CT codelists selected a similar set of patients to Read, with F1 scores exceeding 0.93, and age and sex distributions were similar. The "value set" and "extended" codelists had slightly greater recall but lower precision than "primary" codelists. We were able to represent 257 of the 276 phenotypes by a single concept hierarchy, and for 135 phenotypes, the F1 score was greater than 0.9. CONCLUSIONS: SNOMED CT provides an efficient way to define disease phenotypes, resulting in similar patient populations to manually curated codelists

Estuary and sea-associated wetlands as final sink for organic pollutants: a case study in Sabah, Malaysia

Estuaries and sea-associated wetlands are the final destination for organic pollutants due to their chemical and physical properties. The current research studied Parai River and estuary adjacent to the southern South China Sea in Kota Kinabalu, Sabah. Six samples of surface sediment were taken during January 2012. The samples (top 3 cm) were extracted by Soxhlet using Dichloromethane, subjected to 2 steps of column chromatography for clean-up and fractionation followed by Gas Chromatography-Mass Spectrometry. The results indicated that the highest concentration of alkane in a full range of even and odd carbon numbers is dominant in the estuary and sea-associated wetland. Estuaries receive the highest level of suspended materials due to continuous interaction between marine saline and riverine fresh water. The high amount of Unresolved Complex Mixture (UCM) indicated an incomplete cycle of degradation and decomposition. Terrestrial input was the most dominant natural entry to the study area where C31/C19 ratio was employed. The study concluded that sea-associated wetlands around the estuary may act as the final sink of organic pollutants in the environmen

RDSP: Rapidly Deployable Wireless Ad Hoc System for Post-Disaster Management

In post-disaster scenarios, such as after floods, earthquakes, and in war zones, the cellular communication infrastructure may be destroyed or seriously disrupted. In such emergency scenarios, it becomes very important for first aid responders to communicate with other rescue teams in order to provide feedback to both the central office and the disaster survivors. To address this issue, rapidly deployable systems are required to re-establish connectivity and assist users and first responders in the region of incident. In this work, we describe the design, implementation, and evaluation of a rapidly deployable system for first response applications in post-disaster situations, named RDSP. The proposed system helps early rescue responders and victims by sharing their location information to remotely located servers by utilizing a novel routing scheme. This novel routing scheme consists of the Dynamic ID Assignment (DIA) algorithm and the Minimum Maximum Neighbor (MMN) algorithm. The DIA algorithm is used by relay devices to dynamically select their IDs on the basis of all the available IDs of networks. Whereas, the MMN algorithm is used by the client and relay devices to dynamically select their next neighbor relays for the transmission of messages. The RDSP contains three devices; the client device sends the victim's location information to the server, the relay device relays information between client and server device, the server device receives messages from the client device to alert the rescue team. We deployed and evaluated our system in the outdoor environment of the university campus. The experimental results show that the RDSP system reduces the message delivery delay and improves the message delivery ratio with lower communication overhead.Comment: 23 pages, 12 figures, accepted for publication in Sensors 202

RDSP : Rapidly deployable wireless ad hoc system for post-disaster management

Peer reviewe

netDx: Software for building interpretable patient classifiers by multi-'omic data integration using patient similarity networks

Patient classification based on clinical and genomic data will further the goal of precision medicine. Interpretability is of particular relevance for models based on genomic data, where sample sizes are relatively small (in the hundreds), increasing overfitting risk netDx is a machine learning method to integrate multi-modal patient data and build a patient classifier. Patient data are converted into networks of patient similarity, which is intuitive to clinicians who also use patient similarity for medical diagnosis. Features passing selection are integrated, and new patients are assigned to the class with the greatest profile similarity. netDx has excellent performance, outperforming most machine-learning methods in binary cancer survival prediction. It handles missing data \u2013 a common problem in real-world data \u2013 without requiring imputation. netDx also has excellent interpretability, with native support to group genes into pathways for mechanistic insight into predictive features. The netDx Bioconductor package provides multiple workflows for users to build custom patient classifiers. It provides turnkey functions for one-step predictor generation from multi-modal data, including feature selection over multiple train/test data splits

Selected thiadiazine-thione derivatives attenuate neuroinflammation in chronic constriction injury induced neuropathy

Neuropathic pain refers to a lesion or disease of peripheral and/or central somatosensory neurons and is an important body response to actual or potential nerve damage. We investigated the therapeutic potential of two thiadiazine-thione [TDT] derivatives, 2-(5-propyl-6-thioxo-1, 3, 5-thiadiazinan-3-yl) acetic acid [TDT1] and 2-(5-propyl-2-thioxo-1, 3, 5-thiadiazinan-3-yl) acetic acid [TDT2] against CCI (chronic constriction injury)-induced neuroinflammation and neuropathic pain. Mice were used for assessment of acute toxicity of TDT derivatives and no major toxic/bizarre responses were observed. Anti-inflammatory activity was assessed using the carrageenan test, and both TDT1 and TDT2 significantly reduced carrageenan-induced inflammation. We also used rats for the induction of CCI and performed allodynia and hyperalgesia-related behavioral tests followed by biochemical and morphological analysis using RT-qPCR, immunoblotting, immunohistochemistry and immunofluorescence. Our findings revealed that CCI induced clear-cut allodynia and hyperalgesia which was reversed by TDT1 and TDT2. To determine the function of TDT1 and TDT2 in glia-mediated neuroinflammation, Iba1 mRNA and protein levels were measured in spinal cord tissue sections from various experimental groups. Interestingly, TDT1 and TDT2 substantially reduced the mRNA expression and protein level of Iba1, implying that TDT1 and TDT2 may mitigate CCI-induced astrogliosis. In silico molecular docking studies predicted that both compounds had an effective binding affinity for TNF-α and COX-2. The compounds interactions with the proteins were dominated by both hydrogen bonding and van der Waals interactions. Overall, these results suggest that TDT1 and TDT2 exert their neuroprotective and analgesic potentials by ameliorating CCI-induced allodynia, hyperalgesia, neuroinflammation and neuronal degeneration in a dose-dependent manner

Mitral regurgitation as a phenotypic manifestation of nonphotosensitive trichothiodystrophy due to a splice variant in MPLKIP

Background: Nonphotosensitive trichothiodystrophy (TTDN) is a rare autosomal recessive disorder of neuroectodermal origin. The condition is marked by hair abnormalities, intellectual impairment, nail dystrophies and susceptibility to infections but with no UV sensitivity. Methods: We identified three consanguineous Pakistani families with varied TTDN features and used homozygosity mapping, linkage analysis, and Sanger and exome sequencing in order to identify pathogenic variants. Haplotype analysis was performed and haplotype age estimated. A splicing assay was used to validate the effect of the MPLKIP splice variant on expression. Results: Affected individuals from all families exhibit several TTDN features along with a heart-specific feature, i.e. mitral regurgitation. Exome sequencing in the probands from families ED168 and ED241 identified a homozygous splice mutation c.339 + 1G > A within MPLKIP. The same splice variant co-segregates with TTDN in a third family ED210. The MPLKIP splice variant was not found in public databases, e.g. the Exome Aggregation Consortium, and in unrelated Pakistani controls. Functional analysis of the splice variant confirmed intron retention, which leads to protein truncation and loss of a phosphorylation site. Haplotype analysis identified a 585.1-kb haplotype which includes the MPLKIP variant, supporting the existence of a founder haplotype that is estimated to be 25,900 years old. Conclusion: This study extends the allelic and phenotypic spectra of MPLKIP-related TTDN, to include a splice variant that causes cardiomyopathy as part of the TTDN phenotype

Neoclerodane Diterpenoids from Reehal Fatima, <i>Teucrium yemense</i>

<i>Teucrium yemense</i> (Defl), locally known as Reehal Fatima, is a medicinal plant commonly grown in Saudi Arabia and Yemen. Phytochemical investigation of the aerial parts of <i>T. yemense</i> yielded six new neoclerodane diterpenoids, namely fatimanol A–E (<b>1</b>, <b>2</b>, <b>3</b>, <b>5</b>, and <b>6</b>) and fatimanone (<b>4</b>), and the known teulepicephin (<b>7</b>). As both the <i>Teucrium</i> genus and the related <i>Lamiaceae</i> family have previously been widely reported to possess anthelmintic and antimicrobial activities, the structural and biological characterization of the seven diterpenoids was pursued. The structures of the new compounds were elucidated from their 2D NMR and MS profiles and by comparison to related compounds. The structure of fatimanol D (<b>5</b>) was confirmed by X-ray crystallographic analysis. The new structures contribute to the breadth of knowledge of secondary metabolites in this genus