Miracle-dz/UniFAR-FTUs huggingface dataset:
SU5416 plus hypoxia but not selective VEGFR2 inhibition with cabozantinib plus hypoxia induces pulmonary hypertension in rats: potential role of BMPR2 signaling

SU5416 plus chronic hypoxia causes pulmonary arterial hypertension in rats and is assumed to occur through VEGFR2 inhibition. Cabozantinib is a far more potent VEGFR2 inhibitor than SU5416. Therefore, we hypothesized that cabozantinib plus hypoxia would induce severe pulmonary arterial hypertension in rats. Cell proliferation and pharmacokinetic studies were performed. Rats were given SU5416 or cabozantinib subcutaneously or via osmotic pump and kept hypoxic for three weeks. Right ventricular systolic pressure and hypertrophy were evaluated at days 14 and 28 following removal from hypoxia. Right ventricular fibrosis was evaluated with Picro-Sirius Red staining. Kinome inhibition profiles of SU5416 and cabozantinib were performed. Inhibitor binding constants of SU5416 and cabozantinib for BMPR2 were determined and Nanostring analyses of lung mRNA were performed. Cabozantinib was a more potent VEGFR inhibitor than SU5416 and had a longer half-life in rats. Cabozantinib subcutaneous plus hypoxia did not induce severe pulmonary arterial hypertension. Right ventricular systolic pressure at 14 and 28 days post-hypoxia was 36.8 ± 2.3 mmHg and 36.2 ± 3.4 mmHg, respectively, versus 27.5 ± 1.5 mmHg in normal controls. For cabozantinib given by osmotic pump during hypoxia, right ventricular systolic pressure was 40.0 ± 3.1 mmHg at 14 days and 27.9 ± 1.9 mmHg at 28 days post-hypoxia. SU5416 plus hypoxia induced severe pulmonary arterial hypertension (right ventricular systolic pressure 61.9 ± 6.1 mmHg and 64.9 ± 8.4 mmHg at 14 and 28 days post-hypoxia, respectively). Cabozantinib induced less right ventricular hypertrophy (right ventricular free wall weight/(left ventricular free wall weight + interventricular septum weight) at 14 days post-hypoxia compared to SU5416. Right ventricular fibrosis was more extensive in the SU5416 groups compared to the cabozantinib groups. SU5416 (but not cabozantinib) inhibited BMPR2. Nanostring analyses showed effects on pulmonary gene expression of BMP10 and VEGFR1 in the SU5416 28 days post-hypoxia group. In conclusion, selective VEGFR2 inhibition using cabozantinib plus hypoxia did not induce severe pulmonary arterial hypertension. Severe pulmonary arterial hypertension due to SU5416 plus hypoxia may be due to combined VEGFR2 and BMPR2 inhibition.
The transition to agricultural cultivation of neo-crops may fail to account for wild genetic diversity patterns: insights from the Cape Floristic Region

Aim The global increase in the cultivation of native wild plants has raised concerns regarding potential risks associated with translocating genetic lineages beyond their natural range. This study aimed to investigate whether agricultural cultivation of neo-crops (a) accounts for the levels of genetic diversity present in wild populations, and whether (b) cultivated populations are genetically divergent from wild populations and thus pose a potential threat to wild genetic diversity. Location The Cape Floristic Region (CFR), located along the southern Cape of South Africa. Methods High Resolution Melt analysis (HRM) coupled with Sanger sequencing was used to screen three non-coding chloroplast DNA loci in Cyclopia Vent. (Fabaceae), a CFR endemic neo-crop cultivated for the production of a herbal infusion referred to as Honeybush tea. Wild and cultivated populations for three of three widely cultivated Honeybush species (C. intermedia, C. longifolia, and C. subternata) were screened. Genetic diversity and differentiation were measured and compared between wild and cultivated groups. Results Across all asseccions, a total of 17 haplotypes were detected, four of which were shared between wild and cultivated populations, while the remaining 13 were only detected in wild populations. Genetic diversity and differentiation was significantly higher in wild populations than in cultivated populations. Conclusions If no guidelines exist to facilitate the introduction of native wild plant taxa to a cultivated setting, wild genetic diversity patterns are likely to be compromised by cultivated populations. In the case presented here, cultivation represents a genetic bottleneck, failing to account for rare haplotypes, and may have disrupted species boundaries by initiating interspecific hybridization. More empirical work is required to evaluate the extent to which neo-crop cultivation poses a risk to wild genetic resources in the CFR and globally.
Adherence to a Mediterranean diet and health-related quality of life: a cross-sectional analysis of overweight and obese middle-aged and older adults with and without type 2 diabetes mellitus

Abstract The relationship between adherence to a Mediterranean diet (MedDiet) and health-related quality of life (HRQoL) is unclear, particularly in vulnerable older adults. This cross-sectional analysis explored the association between adherence to a MedDiet and subscales of HRQoL in two independent cohorts of overweight and obese middle-aged to older adults with and without type 2 diabetes mellitus (T2DM). Both cohorts were community-dwelling (T2DM aged ≥ 50 years; non-T2DM aged ≥ 60 years) with a BMI ≥ 25 kg/m2. Adherence to a MedDiet was assessed using the Mediterranean Diet Adherence Screener, and HRQoL was determined using the 36-item short-form health survey. Multiple regression analysis was used to examine the association between adherence to a MedDiet and HRQoL subscales. A total of 152 middle-aged to older adults were included (T2DM: n 87, 71·2 (sd 8·2) years, BMI: 29·5 (sd 5·9) kg/m2; non-T2DM: n 65, 68·7 (sd 5·6) years, BMI: 33·7 (sd 4·9) kg/m2). Mean adherence scores for the entire cohort were 5·3 (sd 2·2) (T2DM cohort: 5·6(sd 2·3); non-T2DM cohort: 4·9 (sd 2·0)). In the adjusted model, using pooled data from both study cohorts, adherence to a MedDiet was significantly associated with the general health subscale of HRQoL (β = 0·223; 95 % CI 0·006, 0·044; P = 0·001). Similar findings were also observed in the T2DM cohort (β = 0·280; 95 % CI 0·007, 0·054; P = 0·001). However, no additional significant associations between adherence to a MedDiet and HRQoL subscales were observed. We showed that adherence to a MedDiet was positively associated with the general health subscale of HRQoL in middle-aged to older adults with T2DM. However, larger longitudinal data in older adults with a wider range of adherence scores, particularly higher adherence, are required to better understand the direction of this relationship.
Development of the Experienced Communication in Dementia Questionnaire: A Qualitative Study

Communication problems with their caregivers are common in people with dementia. Although interventions for improvement of communication are being developed, a tool to measure how participants experience their communication is lacking. The objective of this article is to describe the development of a questionnaire that measures the “experienced communication” of persons with dementia (ECD-P) as well as of their caregivers (ECD-C). Interviews were conducted with five person with dementia—caregiver dyads who had recently received a new communication intervention. Reflexive thematic analysis was performed on the transcripts using ATLAS.ti. Codes were created, categories and themes were identified, and items for the questionnaires were generated. Selection of items and response scales was done in collaboration with the same dyads. The final version was established after pilot testing with seven other dyads and discussion with five experts in the field of dementia care. Analysis of the transcripts resulted in 212 codes and 17 categories within four themes: caregiver competence, social communication, communication difficulties in daily life, and experienced emotions during conversations. The final version of the ECD-P consists of part 1 with 22 items and 4-point Likert scales, and part 2 with two items and 1 to 10 scales. In the final ECD-C (proxy version), part 1 and part 2 are similar to the ECD-P, while a part 3 was added to assess caregivers’ own perspective and emotions (five items). Based on the experiences of people with dementia and their caregivers, we constructed a face-valid questionnaire. This justifies future research to test its clinimetric characteristics.
Resistin is Associated with Inflammation and Renal Function, but not with Insulin Resistance in Type 2 Diabetes

Abstract The aim of the study was to investigate the association of adipokines (resistin, leptin and adiponectin) with obesity, insulin resistance (IR) and inflammation in type 2 diabetes mellitus (T2DM). A total of 284 patients with T2DM were included. Concentrations of resistin, leptin, adiponectin, and inflammatory markers [high sensitivity C-reactive protein (hsCRP), tumor necrosis factor α (TNF-α), and interleukin 6 (IL-6)] were measured and homeostatic model assessment for IR (HOMA-IR) index was calculated. Resistin correlated negatively with estimated glomerular filtration rate (eGFR) and positively with hsCRP, TNF-α, IL-6, and white blood cell count (WBC). Leptin correlated positively with HOMA-IR, whereas adiponectin correlated negatively. Leptin also correlated positively with body mass index (BMI), waist circumference, IL-6, WBC and negatively with eGFR. Adiponectin correlated negatively with waist circumference, WBC, and eGFR. Multivariate logistic regression indicated lower eGFR and higher WBC and IL-6 as independent predictive factors of resistin concentration above the upper quartile (CAQ3), whereas female sex and higher BMI and HOMA-IR of leptin CAQ3, and lower HOMA-IR and older age of adiponectin CAQ3. In conclusion, in contrast to leptin and adiponectin, in T2DM patients, resistin is not associated with BMI and IR, but with inflammation and worse kidney function.
Clinical Features of COVID-19 Patients With Venous Thromboembolism

This study aimed to assess the clinical features of coronavirus disease 2019 (COVID-19) patients with VTE, to help develop preventive measures for venous thromboembolism (VTE in COVID-19) cases. COVID-19 patients admitted to Henan Provincial People’s Hospital were retrospectively analyzed, including 23, 4 and 8 cases with mild to moderate, severe and critical symptoms, respectively. VTE incidence, age at onset, relevant laboratory parameters and prognosis were analyzed. Overall, VTE incidence in the 35 patients was 20.0%, occurring in severe (n = 1) and critical (n = 6) cases. D-dimer showed statistical significance in laboratory examination, representing except a diagnostic index and especial can be a prognostic factor in VTE among COVID-19 patients. Severe and critical COVID-19 cases had significantly reduced platelet counts, with a risk of hemorrhage. During treatment, the risk of both hemorrhage and thrombosis should be considered. VTE occurs in COVID-19 cases, affecting individuals with severe and critical symptoms. Significant D-dimer increase is of great significance in the risk assessment of death in critical cases of COVID-19. Appropriate measures should be taken to prevent VTE during treatment.
Simultaneous Determination of Ten Synthetic Colours in Ice-cream by High Performance Liquid Chromatography

A high performance liquid chromatographic method was developed for the simultaneous determination of 10 synthetic colours such as indigotin,new red,brilliant blue,tatrazine,sunset yellow,amaranth,ponceau 4R,carmoisine,allura red and erythrosine in ice-cream.The optimal extraction conditions and HPLC chromatographic conditions were confirmed by investigating the extracting solvent,mobile phase type and maximum absorption wavelength.The sample was extracted with methanol water solution,and the extract diluted with water was separated on a Symmetry C18(25 cm×4.6 mm×5 μm)column using methanol-20 mmol/L ammonium acetate as mobile phase by gradient elution.The target compounds were confirmed by diode-array detection and quantified by the external standard method.Under the optimal conditions,the calibration curves of 10 synthetic colours showed good linearities in the range of 0.5-10.0 mg/L,with their correlative coefficients more than 0.997. The mean recoveries at 3 spiked levels of 2,10,50 mg/kg ranged from 76% to 108% with RSDs of 0.56%-2.8%. The detection limits were in the range of 0.2-1.0 mg/kg.The method was simple,rapid,sensitive and accurate,and was suitable for the determination of 10 synthetic colours in ice-cream.
Quantized Fuzzy Cooperative Output Regulation for Heterogeneous Nonlinear Multiagent Systems With Directed Fixed/Switching Topologies

This article investigates the cooperative output regulation problem for heterogeneous nonlinear multiagent systems subject to disturbances and quantization. The agent dynamics are modeled by the well-known Takagi–Sugeno fuzzy systems. Distributed reference generators are first devised to estimate the state of the exosystem under directed fixed and switching communication graphs, respectively. Then, distributed fuzzy cooperative controllers are designed for individual agents. Via the Lyapunov technique, sufficient conditions are obtained to guarantee the output synchronization of the resulting closed-loop multiagent system. Finally, the viability of proposed design approaches is demonstrated by an example of multiple single-link robot arms.
Diversity of West Nile and Usutu virus strains in mosquitoes at an international airport in Austria

Abstract Increased globalization and international transportation have resulted in the inadvertent introduction of exotic mosquitoes and new mosquito‐borne diseases. International airports are among the possible points of entry for mosquitoes and their pathogens. We established a mosquito and mosquito‐borne diseases monitoring programme at the largest international airport in Austria and report the results for the first two years, 2018 and 2019. This included weekly monitoring and sampling of adult mosquitoes, and screening them for the presence of viral nucleic acids by standard molecular diagnostic techniques. Additionally, we surveyed the avian community at the airport, as birds are potentially amplifying hosts. In 2018, West Nile virus (WNV) was detected in 14 pools and Usutu virus (USUV) was detected in another 14 pools of mosquitoes (minimum infection rate [MIR] of 6.8 for each virus). Of these 28 pools, 26 consisted of female Culex pipiens/torrentium, and two contained male Culex sp. mosquitoes. Cx. pipiens/torrentium mosquitoes were the most frequently captured mosquito species at the airport. The detected WNV strains belonged to five sub‐clusters within the sub‐lineage 2d‐1, and all detected USUV strains were grouped to at least seven sub‐clusters among the cluster Europe 2; all strains were previously shown to be endemic in Austria. In 2019, all mosquito pools were negative for any viral nucleic acids tested. Our study suggests that airports may serve as foci of arbovirus activity, particularly during epidemic years, and should be considered when designing mosquito control and arbovirus monitoring programmes.
Single-Stage Prediction Models Do Not Explain the Magnitude of Syntactic Disambiguation Difficulty

The disambiguation of a syntactically ambiguous sentence in favor of a less preferred parse can lead to slower reading at the disambiguation point. This phenomenon, referred to as a garden-path effect, has motivated models in which readers initially maintain only a subset of the possible parses of the sentence, and subsequently require time-consuming reanalysis to reconstruct a discarded parse. A more recent proposal argues that the garden-path effect can be reduced to surprisal arising in a fully parallel parser: words consistent with the initially dispreferred but ultimately correct parse are simply less predictable than those consistent with the incorrect parse. Since predictability has pervasive effects in reading far beyond garden-path sentences, this account, which dispenses with reanalysis mechanisms, is more parsimonious. Crucially, it predicts a linear effect of surprisal: the garden-path effect is expected to be proportional to the difference in word surprisal between the ultimately correct and ultimately incorrect interpretations. To test this prediction, we used recurrent neural network language models to estimate word-by-word surprisal for three temporarily ambiguous constructions. We then estimated the slowdown attributed to each bit of surprisal from human self-paced reading times, and used that quantity to predict syntactic disambiguation difficulty. Surprisal successfully predicted the existence of garden-path effects, but drastically underpredicted their magnitude, and failed to predict their relative severity across constructions. We conclude that a full explanation of syntactic disambiguation difficulty may require recovery mechanisms beyond predictability.
Rectal and vaginal tissue from intravenous VRC01 recipients show protection against ex vivo HIV-1 challenge.

BACKGROUND VRC01, a potent, broadly-neutralizing monoclonal antibody, inhibits simian-HIV infection in animal models. HVTN 104 assessed VRC01 safety and pharmacokinetics in humans. We extend the clinical evaluation to determine intravenous-infused VRC01 distribution and protective function at mucosal sites of HIV-1 entry. METHODS Healthy, HIV-1-uninfected men (n=7) and women (n=5) receiving VRC01 every two months provided mucosal and serum samples once, 4-13 days post-infusion. Eleven male and 8 female HIV-seronegative volunteers provided untreated control samples. VRC01 levels were measured in serum, secretions and tissue, and HIV-1 inhibition was determined in tissue explants. RESULTS Median VRC01 levels were quantifiable in serum (96.2 µg/ml or 1.3 pg/ng protein), rectal tissue (0.11 pg/ng protein), rectal secretions (0.13 pg/ng protein), vaginal tissue (0.1 pg/ng protein) and cervical secretions (0.44 pg/ng protein) from all recipients. VRC01/IgG ratios in male serum correlated with those in paired rectal tissue (r=0.893, P=0.012) and rectal secretions (r=0.9643, P=0.003). Ex vivo HIV-1Bal26 challenge infected 4/21 rectal explants from VRC01-infused versus 20/22 from controls (P=0.005); HIV-1 Du422.1 infected 20/21 rectal explants of VRC01 recipients and 12/12 from controls (P=0.639). HIV-1Bal26 infected 0/14 vaginal explants of VRC01 recipients compared to 23/28 control explants (P=0.003). CONCLUSION Intravenous VRC01 distributes into the female genital and male rectal mucosa and retains anti-HIV-1 functionality, inhibiting a highly neutralization-sensitive but not a highly-resistant HIV-1 strain in mucosal tissue. These findings lend insight into VRC01 mucosal infiltration and provide perspective to in vivo protective efficacy. FUNDING National Institute of Allergy and Infectious Diseases and Bill & Melinda Gates Foundation.
Effects of cigarette smoke exposure on pulmonary physiology, muscle strength and exercise capacity in a retrospective cohort with 30,000 subjects

Background The effects of long-term cigarette smoke exposure on pulmonary physiology and how those effects lead to reduced exercise capacity are not well established. Methods We retrospectively analyzed the spirometry, single-breath gas transfer (DLCO), peripheral muscle strength, and maximum exercise capacity data in patients referred to McMaster University Medical Centre for cardiopulmonary exercise testing between 2000 and 2012. Results 29,441 subjects underwent CPET and had a recorded smoking history [58% male, mean age 51.1 years (S.D.±19.6), BMI 27.4 kg/m2(±5.8)]. 7081 (24%) were current or former smokers and were divided into 4 categories by packs years (mean ±S.D.): <10 (5.8±3.3), 10–20 (17.1±2.9), 20–30 (27.1±2.8), 30–40 (37.3±2.8), and >40 (53.9±12.8). Patients with greater cigarette smoke exposure had lower expiratory flow rates (FEV1, FEF50, FEF75, PEFR), DLCO, and maximum power output (MPO) during exercise. There was no association between smoke exposure and muscle strength. Modeling MPO (kpm/min) output as a function of demographic and physiologic variables showed that the data are well explained by muscle strength (kg), FEV1 (L), and DLCO (mmHg/min/mL) in similar magnitude (MPO = 42.7*Quads0.34*FEV10.34 * DLCO0.43; r = 0.84). Conclusions Long-term cigarette smoke exposure is associated with small airway narrowing and impaired diffusion capacity but not with peripheral muscle weakness. The effects of smoking, age, and gender on maximum power output are mediated by reductions in FEV1, muscle strength and DLCO. Exercise capacity in smokers may benefit from therapies targeting all 3 variables.
PagWOX11/12a activates PagCYP736A12 gene that facilitates salt tolerance in poplar

Summary The WUSCHEL‐related homeobox (WOX) transcription factors WOX11 and WOX12 regulate adventitious rooting and responses to stress. The underlying physiological and molecular regulatory mechanisms in salt stress tolerance remain largely unexplored. Here, we characterized the roles of PagWOX11/12a from 84K poplar (Populus alba × P. glandulosa) and the underlying regulatory mechanism in salt stress. PagWOX11/12a was strongly induced by salt stress in roots. Overexpression of PagWOX11/12a in poplar enhanced salt tolerance, as evident by the promotion of growth‐related biomass. In contrast, salt‐treated PagWOX11/12a dominant repression plants displayed reduced biomass growth. Under salt stress conditions, PagWOX11/12a‐overexpressed lines showed higher reactive oxygen species (ROS) scavenging capacity and lower accumulation of hydrogen peroxide (H2O2) than non‐transgenic 84K plants, whereas the suppressors displayed the opposite phenotype. In addition, PagWOX11/12a directly bound to the promoter region of PagCYP736A12 and regulated PagCYP736A12 expression. The activated PagCYP736A12 could enhance ROS scavenging, thus reducing H2O2 levels in roots under salt stress in PagWOX11/12a‐overexpressed poplars. The collective results support the important role of PagWOX11/12a in salt acclimation of poplar trees, indicating that PagWOX11/12a enhances salt tolerance through modulation of ROS scavenging by directly regulating PagCYP736A12 expression in poplar.
Type I interferon is induced by hemolysis and drives antibody-mediated erythrophagocytosis in sickle cell disease.

Patients with sickle cell disease (SCD) suffer from intravascular hemolysis associated vascular injury and tissue damage. Classical monocytes (CMo), which are the most abundant of circulating monocytes, are activated in SCD, but the cause and consequences of activation remain incompletely understood. We found a positive correlation between total plasma heme levels and circulating IFN-α in patients with SCD along with upregulation of the type I Interferon (IFN-I) inducible genes in sort-purified SCD patients' CMo by transcriptome analysis. We demonstrated that hemolysis led to IFN-I expression, predominantly by mouse liver monocyte and macrophages (Mϕ), primarily through Tank kinase binding 1 (TBK1)/IκB kinase-ε (IKKε) but not TLR4. In response to hemolysis-induced IFN-I, mouse CMo migrated to the liver and differentiated into monocyte derived Mϕ, increasing their numbers by 6-fold with acute hemin treatment. Hemolysis-driven IFN-I activity also led to the induction of Fc receptor CD64 expression on monocyte and Mϕ populations, enhancing alloantibody-mediated erythrophagocytosis in SCD both in vivo in mice and in in vitro human cultures. Altogether, these data demonstrate IFN-I response to hemolysis as a novel activation pathway in monocytes and Mϕ in SCD, opening the possibility for development of IFN-I-based diagnostics and therapeutics against alloantibody-mediated erythrophagocytosis.
Mesoporous silica nanosphere supported platinum nanoparticles (Pt@MSN): one-pot synthesis and catalytic hydrogen generation

One-pot synthesis of mesoporous silica nanosphere (MSN) supported platinum nanoparticles (NPs) as catalysts for hydrogen generation from alkaline sodium borohydride is reported. The size of the NPs can somehow be tuned by the pore size of the MSN providing that the metal loading is not high. The catalysts provided a turnover frequency (TOF) of 11 274 h−1 with a hydrogen generation rate (HGR) of 19 L min−1 g−1 Pt.