Miracle-dz/UniFAR-FTUs huggingface dataset:
Arbovirus and insect‐specific virus discovery in Kenya by novel six genera multiplex high‐resolution melting analysis

A broad diversity of arthropod‐borne viruses (arboviruses) of global health concern are endemic to East Africa, yet most surveillance efforts are limited to just a few key viral pathogens. Additionally, estimates of arbovirus diversity in the tropics are likely to be underestimated as their discovery has lagged significantly over past decades due to limitations in fast and sensitive arbovirus identification methods. Here, we developed a nearly pan‐arbovirus detection assay that uses high‐resolution melting (HRM) analysis of RT–PCR products from highly multiplexed assays to differentiate broad diversities of arboviruses. We differentiated 15 viral culture controls and seven additional synthetic viral DNA sequence controls, within Flavivirus, Alphavirus, Nairovirus, Phlebovirus, Orthobunyavirus and Thogotovirus genera. Among Bunyamwera, sindbis, dengue and Thogoto virus serial dilutions, detection by multiplex RT–PCR‐HRM was comparable to the gold standard Vero cell plaque assays. We applied our low‐cost method for enhanced broad‐range pathogen surveillance from mosquito samples collected in Kenya and identified diverse insect‐specific viruses, including a new clade in anopheline mosquitoes, and Wesselsbron virus, an arbovirus that can cause viral haemorrhagic fever in humans and has not previously been isolated in Kenya, in Culex spp. and Anopheles coustani mosquitoes. Our findings demonstrate how multiplex RT–PCR‐HRM can identify novel viral diversities and potential disease threats that may not be included in pathogen detection panels of routine surveillance efforts. This approach can be adapted to other pathogens to enhance disease surveillance and pathogen discovery efforts, as well as the study of pathogen diversity and viral evolutionary ecology.
Drug Sensitivity and Resistance Mechanism in Aspergillus Section Nigri Strains from Japan

ABSTRACT Aspergillus niger and its related species, known as Aspergillus section Nigri, are ubiquitously distributed across the globe and are often isolated from clinical specimens. In Japan, Aspergillus section Nigri is second most often isolated from clinical specimens following Aspergillus fumigatus. We determined the species of Aspergillus section Nigri isolated in Japan by DNA sequencing of partial β-tubulin genes and investigated drug susceptibility by the CLSI M38-A2 method. The collection contained 20 Aspergillus niger, 59 Aspergillus welwitschiae, and 39 Aspergillus tubingensis strains. Drug susceptibility testing revealed 30 to 55% of A. niger, 6.8 to 18.6% of A. welwitschiae, and 79.5 to 89.7% of A. tubingensis isolates to be less susceptible (so-called resistant) to itraconazole (ITC) and/or voriconazole (VRC) according to the epidemiologic cutoff values (ECVs) proposed for A. niger previously. MIC distributions of ITC or VRC showed no remarkable differences between clinical and environmental isolates. When the cyp51A sequences were compared between susceptible and resistant strains, 18 amino acid mutations were specific for resistant isolates of A. niger and A. tubingensis; however, none of them were confirmed to be associated with azole resistance. Three nonrelated A. welwitschiae isolates possessed a partial deletion in cyp51A, likely attributable to being more susceptible to azoles than other isolates. One of five ITC-resistant A. tubingensis isolates showed higher expression of cyp51A than did susceptible strains. Our results show that cyp51A point mutations may have no association with azole resistance but that in some cases the overexpression of cyp51A may lead to the azole resistance in these species.
Numerical and experimental investigation of modal-energy-based damage localization for offshore wind turbine structures

Offshore wind turbine structures are prone to deterioration and damage during their service life in harsh marine environment. To explore highly efficient and robust damage detection methods for offshore wind turbine structures, three well-known modal strain energy indices are reviewed first and then a new index named total modal energy method is proposed. The innovation of the new index is the simultaneous use of modal strain energy and modal kinetic energy. To investigate the feasibility and robustness of the four modal-energy-based methods, numerical and experimental studies are conducted on a tripod-type offshore wind turbine structure with simulated and measured data. It is indicated that all the four modal-energy-based methods work well with limited incomplete modal data, especially for the single-damage cases. While for the cases of multiple damage locations, the new total modal energy index significantly outperforms the traditional modal strain energy indices. Moreover, high robustness is shown for the indices, when the measured mode shapes of undamaged and damaged structures are polluted with the same noise level. However, when their noise levels have some difference, two of the modal strain energy indices turn invalid, but the new total modal energy index still shows stronger robustness. As frequencies are also used in the total modal energy index, its robustness to the noise in modal frequencies is also studied. It is shown that the results are slightly affected by the measurement noise in modal frequencies. Besides, the influence of finite element modeling errors is also investigated with both simulated and experimental data. Results show that all the four modal-energy-based methods are all very stable and insensitive to certain modeling errors. So, finite element model updating is not necessary in the test structure herein.
Use of Single-Nucleotide Polymorphisms and Mammographic Density Plus Classic Risk Factors for Breast Cancer Risk Prediction

Importance Single-nucleotide polymorphisms (SNPs) have demonstrated an association with breast cancer susceptibility, but there is limited evidence on how to incorporate them into current breast cancer risk prediction models. Objective To determine whether a panel of 18 SNPs (SNP18) may be used to predict breast cancer in combination with classic risk factors and mammographic density. Design, Setting, and Participants This cohort study enrolled a subcohort of 9363 women, aged 46 to 73 years, without a previous breast cancer diagnosis from the larger prospective cohort of the PROCAS study (Predicting Risk of Cancer at Screening) specifically to evaluate breast cancer risk-assessment methods. Enrollment took place from October 2009 through June 2015 from multiple population-based screening centers in Greater Manchester, England. Follow-up continued through January 5, 2017. Exposures Genotyping of 18 SNPs, visual-assessment percentage mammographic density, and classic risk assessed by the Tyrer-Cuzick risk model from a self-completed questionnaire at cohort entry. Main Outcomes and Measures The predictive ability of SNP18 for breast cancer diagnosis (invasive and ductal carcinoma in situ) was assessed using logistic regression odds ratios per interquartile range of the predicted risk. Results A total of 9363 women were enrolled in this study (mean [range] age, 59 [46-73] years). Of these, 466 were found to have breast cancer (271 prevalent; 195 incident). SNP18 was similarly predictive when unadjusted or adjusted for mammographic density and classic factors (odds ratios per interquartile range, respectively, 1.56; 95% CI, 1.38-1.77 and 1.53; 95% CI, 1.35-1.74), with observed risks being very close to expected (adjusted observed-to-expected odds ratio, 0.98; 95% CI, 0.69-1.28). A combined risk assessment indicated 18% of the subcohort to be at 5% or greater 10-year risk, compared with 30% of all cancers, 35% of interval-detected cancers, and 42% of stage 2+ cancers. In contrast, 33% of the subcohort were at less than 2% risk but accounted for only 18%, 17%, and 15% of the total, interval, and stage 2+ breast cancers, respectively. Conclusions and Relevance SNP18 added substantial information to risk assessment based on the Tyrer-Cuzick model and mammographic density. A combined risk is likely to aid risk-stratified screening and prevention strategies.
Finely Tuned Asymmetric Platinum(IV) Anticancer Complexes: Structure–Activity Relationship and Application as Orally Available Prodrugs

Platinum(IV) bis‐carboxylates are highly versatile prodrug scaffolds with different axial ligands that can be functionalized while keeping the platinum(II) pharmacophore intact. Using a sequential acylation strategy, we developed a class of PtIV prodrugs of cisplatin with contrasting lipophilic and hydrophilic ligands. We investigated their stability, reduction rates, lipophilicity, aqueous solubility, and antiproliferative efficacies, and assessed for correlations among the parameters that could be useful in drug design. We showed that compounds with high lipophilicity result in better antiproliferative effects in vitro and in vivo, with one of the three compounds tested showing better efficacy than satraplatin against an animal model of colorectal cancer, owing to its higher solubility and lower reduction rates. Our asymmetric PtIV prodrugs may pave the way for a highly predictable, fine‐tuned class of orally available PtIV prodrugs for the treatment of colorectal cancer.
The scaffolding protein NHERF1 regulates the stability and activity of the tyrosine kinase HER2

We examined whether the scaffolding protein sodium-hydrogen exchanger regulatory factor 1 (NHERF1) interacts with the calcium pump PMCA2 and the tyrosine kinase receptor ErbB2/HER2 in normal mammary epithelial cells and breast cancer cells. NHERF1 interacts with the PDZ-binding motif in PMCA2 in both normal and malignant breast cells. NHERF1 expression is increased in HER2-positive breast cancers and correlates with HER2-positive status in human ductal carcinoma in situ (DCIS) lesions and invasive breast cancers as well as with increased mortality in patients. NHERF1 is part of a multiprotein complex that includes PMCA2, HSP90, and HER2 within specific actin-rich and lipid raft-rich membrane signaling domains. Knocking down NHERF1 reduces PMCA2 and HER2 expression, inhibits HER2 signaling, dissociates HER2 from HSP90, and causes the internalization, ubiquitination, and degradation of HER2. These results demonstrate that NHERF1 acts with PMCA2 to regulate HER2 signaling and membrane retention in breast cancers.
Building Interoperable FHIR-Based Vocabulary Mapping Services: A Case Study of OHDSI Vocabularies and Mappings

The OHDSI Common Data Model (CDM) is a deep information model, in which its vocabulary component plays a critical role in enabling consistent coding and query of clinical data. The objective of the study is to create methods and tools to expose the OHDSI vocabularies and mappings as the vocabulary mapping services using two HL7 FHIR core terminology resources ConceptMap and ValueSet. We discuss the benefits and challenges in building the FHIR-based terminology services.
Zhx2 (zinc fingers and homeoboxes 2) regulates major urinary protein gene expression in the mouse liver

The mouse major urinary proteins (Mups) are encoded by a large family of highly related genes clustered on chromosome 4. Mups, synthesized primarily and abundantly in the liver and secreted through the kidneys, exhibit male-biased expression. Mups bind a variety of volatile ligands; these ligands, and Mup proteins themselves, influence numerous behavioral traits. Although urinary Mup protein levels vary between inbred mouse strains, this difference is most pronounced in BALB/cJ mice, which have dramatically low urinary Mup levels; this BALB/cJ trait had been mapped to a locus on chromosome 15. We previously identified Zhx2 (zinc fingers and homeoboxes 2) as a regulator of numerous liver-enriched genes. Zhx2 is located on chromosome 15, and a natural hypomorphic mutation in the BALB/cJ Zhx2 allele dramatically reduces Zhx2 expression. Based on these data, we hypothesized that reduced Zhx2 levels are responsible for lower Mup expression in BALB/cJ mice. Using both transgenic and knock-out mice along with in vitro assays, our data show that Zhx2 binds Mup promoters and is required for high levels of Mup expression in the adult liver. In contrast to previously identified Zhx2 targets that appear to be repressed by Zhx2, Mup genes are positively regulated by Zhx2. These data identify Zhx2 as a novel regulator of Mup expression and indicate that Zhx2 activates as well as represses expression of target genes.
Clinical and Prognostic Analysis of Hypopharyngeal Squamous Cell Carcinoma with Synchronous and Metachronous Multiple Malignancies.

BACKGROUND/AIM To analyze the clinical features and prevalence of synchronous and metachronous second primary malignancies (SPMs) in patients with hypopharyngeal squamous cell carcinoma (HSCC), their associated risk factors, and cause-specific mortality. PATIENTS AND METHODS We retrospectively reviewed 136 patients treated with curative intent at our hospital. Statistical analyses were performed to determine factors predictive of SPM and cause-specific mortality. RESULTS Sixty-three of 136 patients (46.3%) developed SPM; of these, 41 (30.1%) and 42 (30.9%) had synchronous and metachronous SPMs, respectively, with patient overlap. The most common site of synchronous and metachronous SPMs was the oesophagus (65.8% and 24.4%, respectively); the corresponding overall survival rates were 34.1% and 66.5%, respectively. Furthermore, heavy drinking was significantly correlated with synchronous SPM (p<0.001). CONCLUSION Oesophageal cancer surveillance is recommended for patients with HSCC, especially heavy drinkers. Our findings may help identify and properly manage HSCC patients at high risk of SPMs.
Human Beta Defensin 2 Selectively Inhibits HIV-1 in Highly Permissive CCR6+CD4+ T Cells

Chemokine receptor type 6 (CCR6)+CD4+ T cells are preferentially infected and depleted during HIV disease progression, but are preserved in non-progressors. CCR6 is expressed on a heterogeneous population of memory CD4+ T cells that are critical to mucosal immunity. Preferential infection of these cells is associated, in part, with high surface expression of CCR5, CXCR4, and α4β7. In addition, CCR6+CD4+ T cells harbor elevated levels of integrated viral DNA and high levels of proliferation markers. We have previously shown that the CCR6 ligands MIP-3α and human beta defensins inhibit HIV replication. The inhibition required CCR6 and the induction of APOBEC3G. Here, we further characterize the induction of apolipoprotein B mRNA editing enzyme (APOBEC3G) by human beta defensin 2. Human beta defensin 2 rapidly induces transcriptional induction of APOBEC3G that involves extracellular signal-regulated kinases 1/2 (ERK1/2) activation and the transcription factors NFATc2, NFATc1, and IRF4. We demonstrate that human beta defensin 2 selectively protects primary CCR6+CD4+ T cells infected with HIV-1. The selective protection of CCR6+CD4+ T cell subsets may be critical in maintaining mucosal immune function and preventing disease progression.
CIACP: A Correlation- and Iteration- Aware Cache Partitioning Mechanism to Improve Performance of Multiple Coarse-Grained Reconfigurable Arrays

Multiple coarse-grained reconfigurable arrays (CGRA), which are organized in parallel or pipeline to complete applications, have become a productive solution to balance the performance with the flexibility. One of the keys to obtain high performance from multiple CGRAs is to manage the shared on-chip cache efficiently to reduce off-chip memory bandwidth requirements. Cache partitioning has been viewed as a promising technique to enhance the efficiency of a shared cache. However, the majority of prior partitioning techniques were developed for multi-core platform and aimed at multi-programmed workloads. They cannot directly address the adverse impacts of data correlation and computation imbalance among competing CGRAs in multi-CGRA platform. This paper proposes a correlation- and iteration- aware cache partitioning (CIACP) mechanism for shared cache partitioning in multiple CGRAs systems. This mechanism employs correlation monitors (CMONs) to trace the amount of overlapping data among parallel CGRAs, and iteration monitors (IMONs) to track the computation load of each CGRA. Using the information collected by CMONs and IMONs, the CIACP mechanism can eliminate redundant cache utilization of the overlapping data and can also shorten the total execution time of pipelined CGRAs. Experimental results showed that CIACP outperformed state-of-the-art utility-based cache partitioning techniques by up to 16 percent in performance.
Neural Representations of Physics Concepts

We used functional MRI (fMRI) to assess neural representations of physics concepts (momentum, energy, etc.) in juniors, seniors, and graduate students majoring in physics or engineering. Our goal was to identify the underlying neural dimensions of these representations. Using factor analysis to reduce the number of dimensions of activation, we obtained four physics-related factors that were mapped to sets of voxels. The four factors were interpretable as causal motion visualization, periodicity, algebraic form, and energy flow. The individual concepts were identifiable from their fMRI signatures with a mean rank accuracy of . 75 using a machine-learning (multivoxel) classifier. Furthermore, there was commonality in participants’ neural representation of physics; a classifier trained on data from all but one participant identified the concepts in the left-out participant (mean accuracy = .71 across all nine participant samples). The findings indicate that abstract scientific concepts acquired in an educational setting evoke activation patterns that are identifiable and common, indicating that science education builds abstract knowledge using inherent, repurposed brain systems.
Sensitivity and Robustness in Chemical Reaction Networks

For a wide class of chemical reaction networks, including all those governed by detailed balanced mass-action kinetics, we examine the robustness of equilibrium species concentrations against fluctuations in the overall reactant supply. In particular, we present lower bounds on the individual species-concentration sensitivities that derive from reaction network structure alone, independent of kinetic parameters or even of the particular equilibrium state at which sensitivities are calculated. These bounds suggest that, in the class of reaction networks considered here, very high robustness (i.e., very low sensitivities) should be expected only when the various molecules are constructed from a large number of distinct elemental building blocks that appear in high multiplicity or that combine gregariously. This situation is often encountered in biology.
Attitudes of Palestinians Toward Social Work Interventions in Cases of Wife Assault

The study examined the attitudes of Palestinian adults toward social work interventions in cases of husband-to-wife assault (HWA). A survey, using self-administered questionnaires and interviews, was conducted among a random sample of 624 adults from the Palestinian Authority. Results indicate higher levels of support for interventions aimed at helping the couple solve their problems than for interventions aimed at protecting the safety of battered women. However, this trend becomes reversed in cases of repeated and severe HWA. Greater support for interventions aimed at protecting the safety of battered women was found among women versus men and younger versus older adults, as well as among individuals with lower levels of justifying wife abuse and more egalitarian expectations of marriage.
The pattern and magnitude of “in vivo thrombin generation” differ in women with preeclampsia and in those with SGA fetuses without preeclampsia

Abstract Objective: We aimed to determine the differences in the pattern and magnitude of thrombin generation between patients with preeclampsia (PE) and those with a small-for-gestational-age (SGA) fetus. Methods: This cross-sectional study included women in the following groups: (1) normal pregnancy (NP) (n = 49); (2) PE (n = 56); and (3) SGA (n = 28). Maternal plasma thrombin generation (TGA) was measured, calculating: (a) lag time (LT); (b) velocity index (VI); (c) peak thrombin concentration (PTC); (d) time-to-peak thrombin concentration (TPTC); and (e) endogenous thrombin potential (ETP). Results: (1) The median TPTC, VI, and ETP differed among the groups (p = .001, p = .006, p < .0001); 2) the median ETP was higher in the PE than in the NP (p < .0001) and SGA (p = .02) groups; 3) patients with SGA had a shorter median TPTC and a higher median VI than the NP (p = .002, p = .012) and PE (p < .0001, p = .006) groups. Conclusions: (1) Patients with PE had higher in vivo thrombin generation than women with NP and those with an SGA fetus; (2) the difference in TGA patterns between PE and SGA suggests that the latter group had faster TGA, while patients with PE had a longer reaction, generating more thrombin. This observation is important for the identification of a subset of patients who might benefit from low molecular-weight heparin.
The gut microbiome and hypertension

Purpose of review The mammalian mucosal surfaces are densely inhabited by a diverse microbial ecosystem termed the microbiota. Among these highly heterogeneous populations, the largest and richest is the gut microbiota, recently suggested to affect various physiological traits and susceptibility to disease. Novel metagenomic and metabolomic approaches, which have been developed in the past decade, have enabled the elucidation of the contribution of the microbiota to metabolic, immunologic, neurologic and endocrine homeostasis. Recent findings Dysbiosis, the alteration in the gut microbiota composition and function, has been lately associated with the pathogenesis of multifactorial diseases such as obesity, diabetes and cardiovascular disorders. Recent studies have also suggested associations between dysbiosis and essential hypertension, a common chronic medical condition affecting 20% or more of the adult population worldwide, which is considered a major causative factor for heart disease, stroke, chronic renal failure, blindness and dementia. Summary In this review, we discuss the accumulating research pointing to possible interplays between the gut microbiome and hypertension and highlight future prospects by which utilization of microbiome-related techniques may be incorporated into the diagnosis and therapeutic arsenal of hypertension management.