Multicenter registry and test bed for extended outpatient hemodynamic monitoring: the hemodynamic frontiers in heart failure (HF2) initiative

BackgroundHemodynamic Frontiers in Heart Failure (HF2) is a multicenter academic research consortium comprised of 14 US institutions with mature remote monitoring programs for ambulatory patients with heart failure (HF). The consortium developed a retrospective and prospective registry of patients implanted with a wireless pulmonary artery pressure (PAP) sensor.Goals/aimsHF2 registry collects demographic, clinical, laboratory, echocardiographic (ECHO), and hemodynamic data from patients with PAP sensors. The aims of HF2 are to advance understanding of HF and to accelerate development of novel diagnostic and therapeutic innovations.MethodsHF2 includes adult patients implanted with a PAP sensor as per FDA indications (New York Heart Association (NYHA) Class III HF functional class with a prior hospitalization, or patients with NYHA Class II or brain natriuretic peptide (BNP) elevation without hospitalization) at a HF2 member site between 1/1/19 to present. HF2 registry is maintained at University of Kansas Medical Center (KUMC). The registry was approved by the institutional review board (IRB) at all participating institutions with required data use agreements. Institutions report data into the electronic registry database using REDCap, housed at KUMC.ResultsThis initial data set includes 254 patients implanted from the start of 2019 until May 2023. At time of device implant, the cohort average age is 73 years old, 59.8% are male, 72% have NYHA Class III HF, 40% have left ventricular ejection fraction (LVEF) < 40%, 35% have LVEF > 50%, mean BNP is 560 pg/ml, mean N-Terminal pro-BNP (NTproBNP) is 5,490 pg/ml, mean creatinine is 1.65 mg/dl. Average baseline hemodynamics at device implant are right atrial pressure (RAP) of 11 mmHg, pulmonary artery systolic pressure (PASP) of 47 mmHg, pulmonary artery diastolic pressure (PADP) 21 mmHg, mean pulmonary artery pressure (mPAP) of 20 mmHg, pulmonary capillary wedge pressure (PCWP) of 19 mmHg, cardiac output (CO) of 5.3 L/min, and cardiac index (CI) of 2.5 L/min/m2.ConclusionA real-world registry of patients implanted with a PAP sensor enables long-term evaluation of hemodynamic and clinic outcomes in highly-phenotyped ambulatory HF patients, and creates a unique opportunity to validate and test novel diagnostic and therapeutic approaches to HF

Common Genetic Polymorphisms Influence Blood Biomarker Measurements in COPD

Implementing precision medicine for complex diseases such as chronic obstructive lung disease (COPD) will require extensive use of biomarkers and an in-depth understanding of how genetic, epigenetic, and environmental variations contribute to phenotypic diversity and disease progression. A meta-analysis from two large cohorts of current and former smokers with and without COPD [SPIROMICS (N = 750); COPDGene (N = 590)] was used to identify single nucleotide polymorphisms (SNPs) associated with measurement of 88 blood proteins (protein quantitative trait loci; pQTLs). PQTLs consistently replicated between the two cohorts. Features of pQTLs were compared to previously reported expression QTLs (eQTLs). Inference of causal relations of pQTL genotypes, biomarker measurements, and four clinical COPD phenotypes (airflow obstruction, emphysema, exacerbation history, and chronic bronchitis) were explored using conditional independence tests. We identified 527 highly significant (p 10% of measured variation in 13 protein biomarkers, with a single SNP (rs7041; p = 10−392) explaining 71%-75% of the measured variation in vitamin D binding protein (gene = GC). Some of these pQTLs [e.g., pQTLs for VDBP, sRAGE (gene = AGER), surfactant protein D (gene = SFTPD), and TNFRSF10C] have been previously associated with COPD phenotypes. Most pQTLs were local (cis), but distant (trans) pQTL SNPs in the ABO blood group locus were the top pQTL SNPs for five proteins. The inclusion of pQTL SNPs improved the clinical predictive value for the established association of sRAGE and emphysema, and the explanation of variance (R2) for emphysema improved from 0.3 to 0.4 when the pQTL SNP was included in the model along with clinical covariates. Causal modeling provided insight into specific pQTL-disease relationships for airflow obstruction and emphysema. In conclusion, given the frequency of highly significant local pQTLs, the large amount of variance potentially explained by pQTL, and the differences observed between pQTLs and eQTLs SNPs, we recommend that protein biomarker-disease association studies take into account the potential effect of common local SNPs and that pQTLs be integrated along with eQTLs to uncover disease mechanisms. Large-scale blood biomarker studies would also benefit from close attention to the ABO blood group

A survey on Relation Extraction

With the advent of the Internet, the daily production of digital text in the form of social media, emails, blogs, news items, books, research papers, and Q&A forums has increased significantly. This unstructured or semi-structured text contains a huge amount of information. Information Extraction (IE) can extract meaningful information from text sources and present it in a structured format. The sub-tasks of IE include Named Entity Recognition (NER), Event Extraction, Relation Extraction (RE), Sentiment Extraction, Opinion Extraction, Terminology Extraction, Reference Extraction, and so on.One way to represent information in the text is in the form of entities and relations representing links between entities. The Entity Extraction task identifies entities from the text, and the Relation Extraction (RE) task can identify relationships between those entities. Many NLP applications can benefit from relational information derived from natural language, including Structured Search, Knowledge Base (KB) population, Information Retrieval, Question-Answering, Language Understanding, Ontology Learning, etc. This survey covers (1) basic concepts of Relation Extraction; (2) various Relation Extraction methodologies; (3) Deep Learning techniques for Relation Extraction; and (4) different datasets that can be used to evaluate the RE system

Molecular DNA identification of blood sources fed on, for Culicine mosquitoes (Diptera: Culicidae) collected in the Songkhla province, southern Thailand

Culicine mosquitoes are medically important vectors. Therefore, mosquito control measures are a crucial strategy to interrupt disease transmission. Collection of data on mosquito feeding patterns is crucial for developing an effective vector control strategy. The objective of this study was to use molecular biology methods to identify the sources of DNA in mosquito blood meals. The DNA from blood meals in the mosquito stomachs was extracted and amplified with multiplex PCR, using specific primer sets based on the mitochondrial cytochrome b gene, to identify the DNA sources among human, pig, goat, dog, cow, and chicken. Among the 297 mosquito samples collected in the Songkhla province of Thailand, in Aedes spp. mosquitoes the percentages positive for human, dog, pig, chicken, cow, a mixture of 2 vertebrate DNAs, or of 3, and negative (no identified DNA) were 61.90, 2.38, 2.38, 0.60, 0.60, 4.18, 1.20 and 26.79% respectively. In Culex spp. blood meals the rank order was different: fractions positive for chicken, human, dog, cow, goat, pig, a mixture of 2 or 3 vertebrate DNAs, and negative were 40.83, 10.00, 5.00, 4.17, 1.67, 0.83, 8.32, 3.32 and 25.83% respectively. This study shows that feeding behaviors of the two species differ, with most Aedes spp. blood meals containing human blood, while Culex spp. had primarily consumed chicken blood. An improved understanding of the feeding behaviors of mosquitoes could contribute to new, more effective strategies for the control of mosquito populations

Ethyl 2-(3,5-dimethyl-1,1-dioxo-2H-1λ6,2,6-thiadiazin-4-yl)benzoate

In the title compound, C14H16N2O4S, the thiadiazine ring is in a half-boat conformation. The aromatic ring deviates from the plane of this moiety at an angle of 74.6 (2)°. The structure displays intermolecular N—H...O hydrogen bonding [N...O = 2.8157 (16) Å], creating ribbons along the [010] axis. There are also weak C—H...O interactions in the crystal but no π–π stacking

Taxonomic revaluation of the Ahaetulla prasina (H. Boie in F. Boie, 1827) complex from Northeast India: resurrection and redescription of Ahaetulla flavescens (Wall, 1910) (Reptilia: Serpentes: Colubridae)

The taxonomic status of the nominal taxon Dryophis prasinus flavescens Wall, 1910 is reevaluated herein. Based on molecular data generated from fresh collections of Ahaetulla prasina (H. Boie in F. Boie, 1827) auctorum from Northeast India and, additionally, morphological data from museum specimens originating from the same areas, we resurrect this taxon as Ahaetulla flavescens (Wall, 1910) comb. nov. We clarify the status, identity and locations of its type specimens, rediscover, redescribe and illustrate those specimens and also designate a lectotype in order to effect a proper taxonomic redefinition of this nominal taxon. We provide further details on the morphology and diagnosis of this species and elucidate its phylogenetic position. We also provide a summary of the natural history and distribution of this species. Adding to the known cryptic diversity and genetic divergence within Southeast Asian populations, this work also hints at the need for a taxonomic revision of the A. prasina complex. This work complements a previous study on the A. prasina complex focusing on populations in Indonesia. Taken together, these two studies represent phylogenetic reconstructions from different populations of the A. prasina complex across its distribution range, on the Asian mainland and the surrounding islands

Discovery of a Distinct Chemical and Mechanistic Class of Allosteric HIV‑1 Integrase Inhibitors with Antiretroviral Activity

Allosteric integrase inhibitors (ALLINIs) bind to the lens epithelial-derived growth factor (LEDGF) pocket on HIV-1 integrase (IN) and possess potent antiviral effects. Rather than blocking proviral integration, ALLINIs trigger IN conformational changes that have catastrophic effects on viral maturation, rendering the virions assembled in the presence of ALLINIs noninfectious. A high-throughput screen for compounds that disrupt the IN·LEDGF interaction was executed, and extensive triage led to the identification of a <i>t</i>-butylsulfonamide series, as exemplified by <b>1</b>. The chemical, biochemical, and virological characterization of this series revealed that <b>1</b> and its analogs produce an ALLINI-like phenotype through engagement of IN sites distinct from the LEDGF pocket. Key to demonstrating target engagement and differentiating this new series from the existing ALLINIs was the development of a fluorescence polarization probe of IN (FLIPPIN) based on the <i>t-</i>butylsulfonamide series. These findings further solidify the late antiviral mechanism of ALLINIs and point toward opportunities to develop structurally and mechanistically novel antiretroviral agents with unique resistance patterns