Miracle-dz/UniFAR-FTUs huggingface dataset:
Myocardial strain and left ventricular geometry: a meta-analysis of echocardiographic studies in systemic hypertension

Supplemental Digital Content is available in the text Aim: Evidence on systolic dysfunction, as assessed by left ventricular (LV) mechanics, in hypertensive heart disease phenotyped by abnormal LV geometric patterns is still limited. Thus, we performed a systematic meta-analysis of 2D/3D speckle-tracking studies in order to provide an updated comprehensive information on this topic. Methods: The PubMed, OVID-MEDLINE, and Cochrane library databases were analyzed to search for articles published from the inception up to 31 January 2021. Studies were identified by using MeSH terms and crossing the following search items: ‘myocardial strain’, ‘left ventricular mechanics’, ‘speckle tracking echocardiography’, ‘systolic dysfunction’, ‘hypertensive heart disease’, ‘left ventricular hypertrophy’, left ventricular remodeling”, ‘concentric hypertrophy’, ‘eccentric hypertrophy’. Results: Overall, data of 267 normotensive controls and 712 hypertensive patients (234 normal geometry, 97 LV concentric remodeling, 176 eccentric LVH, and 205 concentric LVH) from eight studies were considered. Pooled ejection fraction was similar in normotensives and in the whole group of hypertensive patients: (SMD 0.037 ± 0.05, confidence interval (CI): 0.14/0.07, P = 0.51) as well as in hypertensive subgroups. LVMI, and E/e’ gradually increased from hypertensive patients with normal geometry and concentric remodeling, to patients with eccentric and concentric LVH. LV global longitudinal strain (GLS) was lower in all hypertensive groups compared with normotensive controls, in particular, in the eccentric (SMD 1.14 ± 0.22, CI: 0.69/1.59, P < 0.0001) and concentric LVH group (SMD 1.37 ± 0.21, CI: 0.95/1.79, P < 0.0001). The meta-analysis restricted to hypertensive patients showed that GLS gradually deteriorated from hypertensive patients with normal LV geometry, across those with concentric remodeling, to participants with eccentric and concentric LVH (−19.5 ± 0.6 versus −18.8 ± 0.73 versus −17.6 ± 0.66 versus −16.5 ± 0.6%, P < 0.001 for trend). Statistical significance was reached when GLS of the concentric and eccentric LVH group but not the concentric remodeling was compared with the normal geometry one. Conclusion: The present meta-analysis confirms that GLS performs better than ejection fraction in identifying systolic dysfunction in the hypertension setting. More importantly, it suggests that this occurs in patients with altered LV structure and geometry, such as LVH.
HIV Testing and Counseling at U.S. Substance Use Treatment Facilities: A Missed Opportunity for Early Identification.

OBJECTIVE The objective of this study was to determine the availability and national distribution of HIV testing and counseling at substance use treatment facilities in the United States. METHODS Analyses of data from the 2018 National Survey of Substance Abuse Treatment Services assessed HIV testing and counseling availability in U.S. substance use treatment facilities (excluding those in U.S. territories). Facilities were subcategorized by availability of mental health services and medication for opioid use disorders and compared by using logistic models. Descriptive statistics were calculated to characterize the availability of HIV testing and counseling by state, state HIV incidence, and facility characteristics. RESULTS Among U.S. substance use treatment facilities (N=14,691), 29% offered HIV testing, 53% offered HIV counseling, 23% offered both, and 41% offered neither. Across states, the proportions of facilities offering HIV testing ranged from 9.0% to 62.8%, and the proportion offering counseling ranged from 19.2% to 83.3%. In only three states was HIV testing offered by at least 50% of facilities. HIV testing was significantly more likely to be offered in facilities that offered medication for opioid use disorder (48.0% versus 16.0% in those not offering such medication) or mental health services (31.2% versus 24.1% in those not offering such services). Higher state-level HIV incidence was related to an increased proportion of facilities offering HIV testing. CONCLUSIONS Only three in 10 substance use treatment facilities offered HIV testing in 2018. This finding represents a missed opportunity for early identification of HIV among people receiving treatment for substance use disorders.
RNAi suppression of DNA methylation affects drought stress response and genome integrity in transgenic poplar.

Trees are long-lived organisms continuously adapting to their environments, for which epigenetic mechanisms are likely to play a key role. By downregulation of the chromatin remodeler DECREASED IN DNA METHYLATION 1 (DDM1) in poplar (Populus tremula x Populus alba) RNAi lines, we examined how DNA methylation coordinates genomic and physiological responses to moderate water deficit. We compared the growth and drought response of two RNAi-ddm1 lines to wild-type (WT) trees under well-watered and water deficit/rewatering conditions, and analyzed their methylomes, transcriptomes, mobilomes and phytohormone contents in the shoot apical meristem. The RNAi-ddm1 lines were more tolerant to drought-induced cavitation but did not differ in height or stem diameter growth. About 5,000 differentially methylated regions were consistently detected in both RNAi-ddm1 lines, colocalizing with 910 genes and 89 active transposable elements. Under water deficit conditions, 136 differentially expressed genes were found, including many involved in phytohormone pathways; changes in phytohormone concentrations were also detected. Finally the combination of hypomethylation and drought led to the mobility of two transposable elements. Our findings suggest major roles for DNA methylation in regulation of genes involved in hormone-related stress responses, and the maintenance of genome integrity through repression of transposable elements.
Correlation analysis of expression of CC and CXC chemokines in children with autism spectrum disorder

Abstract To investigate the relationship between the expression of CC and CXC chemokines and autism spectrum disorder (ASD). A total of 62 children with ASD (ASD group) and 60 gender- and age-matched normal children (control group) admitted to our hospital from January 2019 to January 2020 were included in the study. Monocyte chemoattractant protein-1 (MCP-1), macrophage inflammatory protein-1α (MIP-1α), macrophage inflammatory protein-1β (MIP-1β), regulated upon activation, normal T-cell expressed and secreted (RANTES), interleukin-8 (IL-8), monokine induced by interferon (IFN)-γ (MIG), and purified human interferon-γ-induced protein-10 (IP-10) were detected in the ASD group. The correlation between the above indexes and the severity of the ASD group was analyzed. Significantly increased MCP-1 levels (P < .01) along with the markedly decreased MIP-1α and MIP-1β levels (P < .01) were detected in the venous blood of the ASD group compared with the control group. In addition, they exhibited no significant difference (yet a downward trend) in the level of RANTES (P > .05). Children in the ASD group showed significantly decreased IP-10 levels (P < .01); however, they had no noticeable change (yet a decreasing trend) in the levels of IL-8 and MIG (P > .05). MCP-1 level was positively related to the Module 1 scores of Autism Diagnostic Observation Schedule-second edition (ADOS-2), whereas the levels of Childhood Autism Rating Scale MIP-1α, MIP-1β, IL-8, IP-10, and MIG were negatively correlated with the ADOS-2 Module 1 scores (P < .01). However, no significant correlation was found between RANTES and the ADOS-2 Module 1 scores (P > .05). The levels of CC chemokines (MCP-1, MIP-1α, MIP-1β, and RANTES) and CXC chemokines (IL-8, IP-10, and MIG) are positively correlated with the pathogenesis of ASD. Inflammation is an important contributing factor to ASD.
Effectiveness and safety of oral anticoagulation treatment beyond 1 year after venous thromboembolism in patients at intermediate recurrence risk

Effectiveness and safety of long‐term anticoagulation treatment are uncertain in venous thromboembolism (VTE) patients at intermediate risk of recurrence. We examined the association between treatment beyond 1 year and outcomes in a Danish nationwide register‐based study. VTE patients at intermediate risk of recurrence, that is, non‐cancer patients with a first‐time unprovoked VTE, who started oral anticoagulation treatment within 30 days and were alive 365 days after the index VTE were included and followed between 2007 and 2015. Exposure was extended (>365 days) or intermediate (91–365 days) treatment. Analyses were done using Cox regression on a propensity score weighted population. We included 18 609 patients with 7232 (38.9%) receiving extended treatment. Mean duration of follow‐up was 2.6 years. Compared with intermediate treatment, treatment beyond 365 days was associated with a lower weighted risk of recurrent VTE (hazard ratio [HR] 0.56, 95% confidence interval [CI] 0.49–0.65) and all‐cause mortality (HR 0.81, 95% CI 0.72–0.90) and an increased risk of major bleeding (HR 1.87, 95% CI 1.58–2.22). In conclusion, extended anticoagulation treatment (predominantly warfarin) beyond 1 year was in real‐life settings associated with a lower risk of recurrent VTE and all‐cause mortality among VTE patients with an intermediate risk of recurrence. However, an increased bleeding risk should be considered.
Inflammatory and coagulatory markers and exposure to different size fractions of particle mass, number and surface area air concentrations in the Swedish hard metal industry, in particular to cobalt

Abstract Purpose To study the relationship between inhalation of airborne particles and cobalt in the Swedish hard metal industry and markers of inflammation and coagulation in blood. Methods Personal sampling of inhalable cobalt and dust were performed for subjects in two Swedish hard metal plants. Stationary measurements were used to study concentrations of inhalable, respirable, and total dust and cobalt, PM10 and PM2.5, the particle surface area and the particle number concentrations. The inflammatory markers CC16, TNF, IL-6, IL-8, IL-10, SAA and CRP, and the coagulatory markers FVIII, vWF, fibrinogen, PAI-1 and D-dimer were measured. A complete sampling was performed on the second or third day of a working week following a work-free weekend, and additional sampling was taken on the fourth or fifth day. The mixed model analysis was used, including covariates. Results The average air concentrations of inhalable dust and cobalt were 0.11 mg/m3 and 0.003 mg/m3, respectively. For some mass-based exposure measures of cobalt and total dust, statistically significant increased levels of FVIII, vWF and CC16 were found. Conclusions The observed relationships between particle exposure and coagulatory biomarkers may indicate an increased risk of cardiovascular disease.
Effect of rK39 testing in guiding treatment initiation and outcome in patients with visceral leishmaniasis in Ethiopia: A prospective cohort study

Background The rapid diagnostic test (RDT) rK39 is currently being used for routine diagnosis of visceral leishmaniasis (VL) in East Africa. However, continuous monitoring of the performance of the assay, in particular its impact on the clinical decision in initiating anti-leishmanial treatment and outcomes remains needed as there are concerns about the diagnostic performance of this test. Methods VL patients prospectively enrolled in a diagnostic trial and with rK39 RDT were included. We evaluated the effect of rK39 testing in guiding treatment initiation and outcome. On the basis of rK39 RDT test result as well as clinical case definition for VL and microscopy examination, the clinicians decide whether to initiate VL therapy or not. Poisson regression models were used to identify factors associated with a decision to initiate VL therapy. In addition, treatment outcomes of those who received VL therapy were compared to those who received non-VL treatment. Results Of 324 VL suspects enrolled, 184 (56.8%) were rK39+ and 140 (43.2%) were rK39‒. In addition, microscopy exam was done on tissue aspirates from a sub-population (140 individuals), which is 43.2% of the suspected cases, comprising of 117 (63.6%) rK39+ and only 23 (16.4%) rK39‒ cases. Of those with microscopy examination, only 87 (62.1%) were found positive. Among 184 (56.8%) patients without microscopy, 67 (36.4%) were rK39+, of whom 83 (65.9%) were positive by microscopy, 21 (16.7%) were negative by microscopy and 22 (17.5%) had no microscopy results. On the other hand, of those who did not receive VL treatment 58/189 (30.7%) were rK39+ and 131 (69.3%) were rK39‒. Of the rK39+ cases who did not receive VL therapy, only 1 (1.7%) patient was microscopy positive, 12 (20.7%) were negative and 45 (77.6%) patients had no microscopy result. Of the rK39‒ cases (n = 131) who did not receive VL treatment, 16 were microscopy negative and 115 without microscopy exams. Whereas positive rK39 result [adjusted Relative Risk (aRR) 0.69; 95% CI: 0.49–0.96, p = 0.029] and positive microscopy results (aRR 0.03; 95% CI: 0.00–0.24, p = 0.001) were independently associated with VL treatment, having confirmed diagnosis other than VL (aRR 1.64; 95% CI: 1.09–2.46, p = 0.018) was independently associated with initiation of non-VL therapy. The proportion of rK39+ patients who received non-VL treatment with no improvement outcome was significantly higher when compared to those who received VL treatment (24.1%, 95% CI: 14.62–37.16 vs. 11.9%, 95%CI: 7.26–18.93; p<0.0001). Conclusion The study shows that a significant proportion of patients with rK39+ results were undertreated. Failure to do microscopy was associated with lack of improved clinical outcome. Including an additional simple point-of-care assay in the diagnostic work-up is urgently needed to correctly identify VL cases and to prevent morbidity and mortality associated with the disease.
Bacterial Metal Resistance: Coping with Copper without Cooperativity?

In Escherichia coli and other Gram-negative bacteria, tripartite efflux pumps (TEPs) span the entire cell envelope and serve to remove noxious molecules from the cell. CusBCA is a TEP responsible for copper and silver detoxification in E. coli powered by the resistance-nodulation-cell division (RND) transporter, CusA. ABSTRACT In Escherichia coli and other Gram-negative bacteria, tripartite efflux pumps (TEPs) span the entire cell envelope and serve to remove noxious molecules from the cell. CusBCA is a TEP responsible for copper and silver detoxification in E. coli powered by the resistance-nodulation-cell division (RND) transporter, CusA. In a recent study, Moseng et al. (M. A. Moseng, M. Lyu, T. Pipatpolkai, P. Glaza, et al., mBio 12:e00452-21, 2021, https://dx.doi.org/10.1128/mBio.00452-21) obtained cryo-electron microscopy (cryo-EM) structures of CusA trimers in the presence of copper. The multiple conformations revealed suggest that the three monomers function independently within the CusA trimer, contrary to the cooperative mechanism proposed for the multidrug exporting RND transporter, AcrB. The work prompts consideration of the mechanism of this class of transporter and provides a basis to underpin further studies of TEPs important for bacterial survival.
An overview of zinc oxide nanoparticles produced by plant extracts for anti-tuberculosis treatments.

Tuberculosis (TB), induced by Mycobacterium tuberculosis (MTB), is a fatal infectious disease that kills millions of lives worldwide. The emergence of drug-resistant and multidrug-resistant cases is regarded as one of the most challenging threats to TB control due to the low cure rate. Therefore, TB and drug-resistant TB epidemics urge us to explore more effective therapies. The increasing knowledge of nanotechnology has extended to some nanomedicines for disease treatment in the clinic, which also provides novel possibilities for nano-based medicines for TB treatment. Zinc oxide nanoparticles (ZnO NPs) have gained increasing attention for anti-bacterial uses based on their strong ability to induce reactive oxidative species (ROS) and release bactericidal Zinc ions (Zn2+), which are expected to act as novel strategies for TB and drug-resistant TB treatment. Some active herbal medicines from plant extracts have been widely reported to show attractive anti-bacterial activity for infectious treatment, including TB. Here, we summarize the synthesis of ZnO NPs using plant extracts (green synthesized ZnO NPs) and further discuss their potentials for anti-TB treatments. This is the first review article discussing the anti-TB activity of ZnO NPs produced using plant extracts, which might contribute to the further applications of green synthesized ZnO NPs for anti-TB and drug-resistant TB treatment.
Recent updates on Wnt signaling modulators: a patent review (2014-2020)

ABSTRACT Introduction: Wnt signaling is a signal transduction pathway that plays a vital role in embryonic development and normal tissue preservation. Dysfunction of it gives rise to various diseases like cancer, Alzheimer's, metabolic and skeletal disorders, kidney and liver disease, etc. Thus, targeting Wnt pathway can be a potential approach to design and develop novel therapeutic classes. Areas covered: Authors provided an overview of Wnt modulators from 2014 to 2020. Different heterocyclic scaffolds and their pharmacology from a total of 104 PCT applications have been summarized. Expert opinion: The scientific community is working extensively to bring first in the class molecule to the market which targets Wnt pathway. Lorecivivint, Wnt inhibitor, for the treatment of knee Osteoarthritis and SM-04554, Wnt activator, for the treatment of androgenetic alopecia are currently under Phase III. Other molecules, LGK-974, RXC-004, ETC-159, CGX-1321, PRI-724, CWP-232291 and BC-2059 are also under different stages of clinical development for the treatment of cancer. Antibody based Wnt modulator, OTSA101-DTPA-90Y is currently under Phase I for the treatment of Relapsed or Refractory Synovial Sarcoma while OMP-18R5 is under Phase I for Metastatic Breast Cancer. Ongoing preclinical/clinical trials will define the role of the Wnt pathway in different therapeutic areas and open new opportunities.
B-CePs as cross-linking probes for the investigation of RNA higher-order structure

Abstract Elucidating the structure of RNA and RNA ensembles is essential to understand biological functions. In this work, we explored the previously uncharted reactivity of bis-chloropiperidines (B-CePs) towards RNA. We characterized at the molecular level the different adducts induced by the fast reacting compound B-CeP 1 with RNA. Following an approach based on solution thermal melting coupled with ESI mass spectrometry (STHEM-ESI), we proved the ability of B-CePs to induce inter-molecular cross-links between guanines in double stranded RNA. These results open the possibility of using B-CePs as structural probes for investigating higher-order structures, such as the kissing loop complex established by the dimerization initiation site (DIS) of the HIV-1 genome. We confirmed the potential of B-CePs to reveal the identity of RNA structures involved in long-range interactions, expecting to benefit the characterization of samples that are not readily amenable to traditional high-resolution techniques, and thus promoting the elucidation of pertinent RNA systems associated with old and new diseases.
Association of a Sweetened Beverage Tax With Purchases of Beverages and High-Sugar Foods at Independent Stores in Philadelphia

Key Points Question How has the 2017 Philadelphia beverage tax factored into longer-term changes in beverage prices and purchases in independent food retail stores based on observational data? Findings This cross-sectional study found that, 2 years after tax implementation, price audits of stores showed 137% of the tax was passed through to prices and bag checks indicated a 42% decline in volume of taxed beverages purchased in Philadelphia compared with Baltimore. Total calories purchased from beverages and high-sugar foods declined, suggesting food substitution did not offset beverage declines. Meaning These findings suggest a city-level beverage excise tax was associated with persistent declines in purchases of sweetened drinks and calories from sugar in independent stores.
Electroacupuncture alleviates spatial memory deficits in METH withdrawal mice by enhancing astrocyte‐mediated glutamate clearance in the dCA1

Methamphetamine (METH) elicits endogenous glutamate (Glu) in the brain, which could partially explain METH‐induced memory deficits. Here, we investigated the therapeutic effects of electroacupuncture (EA) on spatial memory deficits in METH withdrawal mice and its potential synaptic mechanisms. We found that EA at acupoints ‘Baihui’ and ‘Yintang’ ameliorated the impaired spatial memory in METH withdrawal mice. In parallel, EA attenuated the Glu levels in vivo and suppressed the neuronal activities within dCA1 of METH withdrawal mice, as indicated by the decreasing c‐Fos levels and the amplitude of mEPSP. In the dCA1, EA decreased A1‐like astrocytes but increased astrocytic glutamatergic transporting molecules including glutamate transporter 1 and glutamine synthase. However, EA seemed to have no effects on presynaptic Glu transmission from the dCA3, as evidenced by the similiar levels of c‐Fos in the dCA3 neurons, synaptic vesicular markers of dCA3 neural terminals and values of paired‐pulse ratio in the dCA1 neurons between EA‐treated and sham EA‐treated METH withdrawal mice. These findings suggest that EA might normalize the dCA1 Glu levels at least in part through enhancing astrocyte‐mediated Glu clearance. Taken together, astrocytes might be a novel target for developing therapeutic interventions against the impaired memory behaviours in METH users, and EA represents a promising non‐invasive therapeutic strategy for the management of drug‐caused memory deficits.
Can sodium glucose cotransporter 2 (SGLT-2) inhibitors be beneficial in patients with acute myocardial infarction?

The sodium-glucose cotransporter 2 inhibitors (SGLT2i) empagliflozin, dapagliflozin, and canagliflozin have shown impressive beneficial effects in patients with type-2 diabetes mellitus in mandatory cardiovascular outcome trials. Retrospective data analysis revealed signals that pointed towards positive effects independent of the antidiabetic effects. This could be confirmed for empagliflozin and dapagliflozin in circumstances of chronic heart failure with reduced ejection fraction alone, where rates for hospitalization for heart failure and cumulative major adverse cardiovascular events were reduced in a similar extend in patients with and without diabetes mellitus in corresponding outcome trials. Cardiac remodelling following myocardial infarction leads to heart failure with reduced ejection fraction in many patients and aggravates morbidity and mortality. Clinical data of SGLT2i treatment after acute myocardial infarction is sparse. This review focuses on available experimental data on the effects of SGLT2i used before, during, and after myocardial infarction as well as already published and currently ongoing clinical trials.