Miracle-dz/UniFAR-FTUs huggingface dataset:
The protected tree Dimorphandra wilsonii (Fabaceae) is a population of inter-specific hybrids: recommendations for conservation in the Brazilian Cerrado/Atlantic Forest ecotone.

BACKGROUNDS AND AIMS Dimorphandra wilsonii Rizzini, a critically endangered and protected tree, has a restricted distribution in the ecotone between the Cerrado and the Atlantic Forest in southeastern Brazil. In this area, it co-occurs with D. mollis Benth. , a common tree from the Cerrado, and D. exaltata Schott. , a rare tree from the Atlantic Forest. Previous studies of D. wilsonii indicated heterozygosity excess at the individual level. Field observation of some intermediate phenotypes between D. wilsonii and both congeners suggests hybridization of D. wilsonii with D. mollis and/or D. exaltata. Here, we tested the hypothesis that D. wilsonii may be originated from hybridization between D. exaltata and D. mollis. We also performed cytogenetic analysis to examine if the heterozygote excess could be explained by polyploidy in D. wilsonii. METHODS We evaluated the genetic diversity and population structure of D. wilsonii using eleven nuclear SSRs genotyped in 152 individuals sampled across the taxon's range. We performed comparative genetic analyses using overlapping SSR markers between D. wilsonii and previously published SSR data in D. mollis and D. exaltata to perform a series of allelic comparisons, multivariate and Bayesian analysis. KEY RESULTS Our results suggest that D. wilsonii individuals most likely correspond to F1 hybrids between D. exaltata and D. mollis. Cytogenetic analysis indicated that D. wilsonii is diploid with the same chromosome number as D. mollis (2n = 2x = 28). CONCLUSIONS Our study raises questions about the taxonomic status and the evolutionary future of D. wilsonii. We suggest that the conservation and management strategy for D. wilsonii should be revised and that it should take into account both parental Dimorphandra species in the ecotone, with special emphasis on the threatened D. exaltata. Finally, this study highlights the value of genetic information for the design of conservation strategies.
Bailout bypass surgery for complications of coronary interventions

Background Mechanical complications of percutaneous coronary interventions are treated percutaneously in most cases. If the rescue intervention is unsuccessful, bailout bypass surgery is necessary to restore the coronary flow. The surgical risk in these cases is higher than that of patients operated on for other indications. The aim of our study was to characterize patients who underwent surgical treatment at our institution and to compare their long-term outcomes with patients who underwent emergency bypass surgery for other indications. Methods We analyzed 707 consecutive patients who underwent isolated emergency bypass surgery at our institution from 2007 to 2015. In 44 of these cases, the surgery was necessitated by mechanical complications of percutaneous coronary interventions. There were 31 coronary dissections, 5 entrapped guidewires, and 8 coronary perforations. We compared patients in these three groups with one another. Follow-up was performed to assess long-term outcomes. Results The median age of the cohort was 68 years (range 59–75 years), and 36 (81.8%) patients presented in cardiogenic shock. Thirty-seven (84.1%) patients had history of a percutaneous coronary intervention. The courses were typical for bypass patients. The long-term survival was similar in all three subgroups (p = 0.16). The survival profiles within our sample did not differ significantly from that in patients who underwent emergency bypass surgery for other indications. Conclusions Surgical risk and short- and long-term outcomes of patients undergoing emergency bypass surgery due to mechanical complications of percutaneous coronary interventions are similar to those of patients receiving the same surgery for other indications.
Discordant responses of plasma low-density lipoprotein cholesterol and lipoprotein(a) to alirocumab: A pooled analysis from 10 ODYSSEY Phase 3 studies.

AIMS Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors consistently reduce low-density lipoprotein cholesterol (LDL-C) by 50-60% and lipoprotein(a) (Lp(a)) by 20-30%, but the mechanism of Lp(a) lowering remains unclear. If Lp(a) is cleared by the LDL receptor, similar to LDL-C, then one would expect PCSK9 inhibition to induce a concordant LDL-C/Lp(a) response in an approximately 2:1 ratio. We aim to determine the prevalence of discordant plasma LDL-C/Lp(a) response to the PCSK9 inhibitor alirocumab. METHODS This is a post hoc, pooled analysis of 10 randomized controlled trials from the ODYSSEY Phase 3 clinical trial program for alirocumab. Patients enrolled in the trials were high cardiovascular risk and/or with heterozygous familial hypercholesterolemia. The primary end point was prevalence of discordant LDL-C/Lp(a) response to alirocumab at 24 weeks. Discordant response was defined as LDL-C reduction >35% and Lp(a) reduction ≤10%, or LDL-C reduction ≤35% and Lp(a) reduction >10%. RESULTS Of the 1709 patients in the pooled study cohort, 62.4% were male, and the mean age was 59.2 (SD: 11.0) years. Baseline mean LDL-C was 126.5 (SD: 46.3) mg/dL and baseline median Lp(a) was 46.9 (interquartile range: 21.8-89.0) mg/dL. Total prevalence of discordant LDL-C/Lp(a) response was 21.5% (12.6% with LDL-C >35% reduction and Lp(a) ≤10% reduction; 8.9% with LDL-C ≤35% reduction and Lp(a) >10% reduction). Baseline Lp(a) and familial hypercholesterolemia status did not affect discordance. CONCLUSION A high prevalence of discordant LDL-C/Lp(a) response was observed with alirocumab, further suggesting that PCSK9 inhibitor therapy with alirocumab reduces plasma Lp(a) through alternative pathways to LDL receptor clearance.
Piperine Inhibits TGF-β Signaling Pathways and Disrupts EMT-Related Events in Human Lung Adenocarcinoma Cells

Background: Piperine, an amide extracted from the Piper spices, exhibits strong anti-tumor properties. However, its effect on the epithelial–mesenchymal transition (EMT) process has never been investigated. Herein, we evaluate the toxic effect of piperine on lung adenocarcinoma (A549), breast adenocarcinoma (MDA-MB-231) and hepatocellular carcinoma (HepG2) cell lines, as well as its ability to inhibit EMT-related events induced by TGF-β1 treatment. Methods: The cell viability was investigated by MTT assay. Protein expression was evaluated by Western blot. Gene expression was monitored by real-time PCR. Zymography assay was employed to detect metalloproteinase (MMP) activity in conditioned media. Cell motility was assessed by the wound-healing and phagokinetic gold sol assays. Results: The results revealed that piperine was cytotoxic in concentrations over 100 µM, showing IC50 values for HepG2, MDA-MB-231 and A549 cell lines of 214, 238 and 198 µM, respectively. In order to investigate whether piperine would reverse the TGF-β1 induced-EMT, the A549 cell line was pretreated with sublethal concentrations of the natural amide followed by the addition of TGF-β1. Besides disrupting EMT-related events, piperine also inhibited both ERK 1/2 and SMAD 2 phosphorylation. Conclusions: These results suggest that piperine might be further used in therapeutic strategies for metastatic cancer and EMT-related disorders.
Influence of Rotor Dynamic Scattering on Helicopter Radar Cross-Section

With the continuous improvement and development of armed helicopters, the research on their stealth characteristics has become more and more in depth. In order to obtain the complex effect of stealth characteristics caused by the high-speed rotation of rotor-like components, a dynamic scattering method (DSM) is presented. Rotation speed, azimuth, elevation angle, pitching angle, and rolling angle are studied and discussed in detail. The results show that the electromagnetic scattering characteristics of the main rotor and tail rotor are dynamic and periodic. This period characteristic is related to the rotation speed and attitude angle of the rotor. The radar cross-section (RCS) of the helicopter varies greatly at different observation angles and attitude angles, but the dynamic electromagnetic scattering effect caused by the main rotor and tail rotor cannot be ignored. The presented DSM is effective and efficient for studying the dynamic RCS of the rotor-type parts of a helicopter or the whole machine.
A Genome-Wide Association Study Identifies Two Novel Susceptible Regions for Squamous Cell Carcinoma of the Head and Neck

Two novel risk loci for SCCHN in non-Hispanic white individuals highlight the importance of immunologic mechanism in the disease etiology. To identify genetic variants for risk of squamous cell carcinoma of the head and neck (SCCHN), we conducted a two-phase genome-wide association study consisting of 7,858,089 SNPs in 2,171 cases and 4,493 controls of non-Hispanic white, of which, 434,839 typed and 7,423,250 imputed SNPs were used as the discovery. SNPs with P < 1 × 10−3 were further validated in the OncoArray study of oral and pharynx cancer (5,205 cases and 3,232 controls of European ancestry) from databases of Genotypes and Phenotypes. Meta-analysis of the discovery and replication studies identified one novel locus 6p22.1 (P = 2.96 × 10−9 for the leading rs259919) and two cancer susceptibility loci 6p21.32 (rs3135001, HLA-DQB1) and 6p21.33 (rs1265081, CCHCR1) associated with SCCHN risk. Further stratification by tumor site revealed four known cancer loci (5p15.33, 6p21.32, 6p21.33, and 2p23.1) associated with oral cavity cancer risk and oropharyngeal cancer risk, respectively. In addition, one novel locus 18q22.2 (P = 2.54 × 10−9 for the leading SNP rs142021700) was identified for hypopharynx and larynx cancer risk. For SNPs in those reported or novel loci, we also performed functional annotations by bioinformatics prediction and expression quantitative trait loci analysis. Collectively, our identification of four reported loci (2p23.1, 5p15.33, 6p21.32, and 6p21.33) and two novel loci (6p22.1 and 18q22.2) for SCCHN risk highlight the importance of human leukocyte antigen loci for oropharyngeal cancer risk, suggesting that immunologic mechanisms are implicated in the etiology of this subset of SCCHN. Significance: Two novel risk loci for SCCHN in non-Hispanic white individuals highlight the importance of immunologic mechanism in the disease etiology.
Improving emotion recognition in anorexia nervosa: An experimental proof-of-concept study.

OBJECTIVE Previous research has found increasing evidence for difficulties in emotion recognition ability (ERA) and social cognition in anorexia nervosa (AN), and recent models consider these factors to contribute to the development and maintenance of the disorder. However, there is a lack of experimental studies testing this hypothesis. Therefore, the present proof-of-concept study examined whether ERA can be improved by a single session of a computerized training in AN, and whether this has short-term effects on eating disorder symptoms. METHOD Forty inpatients (22.20 ± 7.15 years) with AN were randomly assigned to receive a single session of computerized training of ERA (TERA) or a sham training (training the recognition of different types of clouds). ERA, self-reported eating disorder symptoms, and body mass index (BMI) were assessed within 3 days before and after training. RESULTS After training, both groups showed improved ERA, reduced self-reported eating disorder symptoms, and an increased BMI. As compared to patients in the control group, patients who received TERA showed greater improvements in ERA and self-reported eating disorder symptoms. DISCUSSION ERA can be effectively trained in patients with AN. Moreover, short-term improvements in self-reported eating disorder symptoms provide tentative support for the hypothesis that difficulties in ERA contribute to the maintenance of AN, and that specific trainings of ERA hold promise as an additional component in AN treatment. Future studies are needed to replicate these findings in larger samples, and to investigate long-term effects and transfer into real-world settings.
Awareness and knowledge about HPV infection and HPV vaccination among women undergoing cytology and colposcopy in Serbian cervical cancer counseling center.

PURPOSE Understanding target groups' awareness and knowledge regarding the human papillomavirus (HPV) and the HPV vaccine is essential for planning the screening and vaccination programs and attaining adequate vaccination coverage. The aim of this study was to estimate awareness and knowledge about HPV infection and the HPV vaccine and to assess factors associated with HPV awareness, HPV vaccine awareness and high HPV-related knowledge among women undergoing cervical cancer screening in Serbia. METHODS A cross-sectional study was conducted between January and June 2013 at the Obstetrics and Gynecology Clinic "Narodni Front" in Belgrade, Serbia. HPV awareness, HPV vaccine awareness, and HPV-related knowledge of women undergoing cervical cancer screening were estimated by the means of structured, self-administered questionnaire. RESULTS The median age of respondents was 36.0 years (range 18-65). Of 324 women participating in the study, 196 (60.5%) had heard of HPV while 95 (29.3%) had heard of the HPV vaccine. The median HPV-related knowledge score was 7 (interquartile range 4.8). Type of occupation and having an increasing number of lifetime sexual partners were associated with HPV awareness, while having no children was associated with HPV vaccine awareness. High HPV knowledge score was associated with younger age and type of occupation. CONCLUSIONS Women undergoing cervical cancer screening in Serbia have moderate awareness of HPV infection and low awareness of HPV vaccine. However, it is promising that those who heard of HPV have high knowledge about it.
The neural mechanisms of threat and reconciliation efforts between Muslims and non-Muslims

ABSTRACT To reduce the escalation of intergroup conflict, it is important that we understand the processes related to the detection of group-based threat and reconciliation. In the present study, we investigated the neural mechanisms of such processes using functional Magnetic Resonance Imaging (fMRI). Functional neuroimaging techniques may shed light on quick, automatic responses to stimuli that happen outside of conscious awareness and are thus increasingly difficult to quantify relying only on participants’ self-reported experiences. They may further provide invaluable insight into physiological processes occurring in situations of sensitive nature, whereby participants–deliberately or not–may withhold their honest responses due to social desirability. Non-Muslim Western Caucasian participants watched short video clips of stereotypical Middle-Eastern Muslim males threatening their ingroup, offering reconciliation to the ingroup, or making a neutral statement. Threatening statements led to increased activation in the amygdala, insula, supramarginal gyrus, and temporal lobe. Reconciliation efforts led to increased activation in the prefrontal cortex, anterior cingulate gyrus, and caudate. The results suggest that threat detection is a relatively automatic process while evaluating and responding to reconciliation offers requires more cognitive efforts. The implications of these findings and future research directions are discussed.
Are the processes of DNA replication and DNA repair reading a common structural chromatin unit?

ABSTRACT Decades of investigation on genomic DNA have brought us deeper insights into its organization within the nucleus and its metabolic mechanisms. This was fueled by the parallel development of experimental techniques and has stimulated model building to simulate genome conformation in agreement with the experimental data. Here, we will discuss our recent discoveries on the chromatin units of DNA replication and DNA damage response. We will highlight their remarkable structural similarities and how both revealed themselves as clusters of nanofocal structures each on the hundred thousand base pair size range corresponding well with chromatin loop sizes. We propose that the function of these two global genomic processes is determined by the loop level organization of chromatin structure with structure dictating function. Abbreviations: 3D-SIM: 3D-structured illumination microscopy; 3C: chromosome conformation capture; DDR: DNA damage response; FISH: fluorescent in situ hybridization; Hi-C: high conformation capture; HiP-HoP: highly predictive heteromorphic polymer model; IOD: inter-origin distance; LAD: lamina associated domain; STED: stimulated emission depletion microscopy; STORM: stochastic optical reconstruction microscopy; SBS: strings and binders switch model; TAD: topologically associated domain Graphical abstract Landmarks of structural organization of chromatin and their relationship with metabolic functions.
Functional Features of TREHALOSE-6-PHOSPHATE SYNTHASE1, an Essential Enzyme in Arabidopsis[OPEN]

Tre6P synthesis by TPS1 is essential for embryogenesis and postembryonic growth in Arabidopsis, and appropriate Suc signaling by Tre6P is dependent on the noncatalytic domains of TPS1. In Arabidopsis (Arabidopsis thaliana), TREHALOSE-6-PHOSPHATE SYNTHASE1 (TPS1) catalyzes the synthesis of the sucrose-signaling metabolite trehalose 6-phosphate (Tre6P) and is essential for embryogenesis and normal postembryonic growth and development. To understand its molecular functions, we transformed the embryo-lethal tps1-1 null mutant with various forms of TPS1 and with a heterologous TPS (OtsA) from Escherichia coli, under the control of the TPS1 promoter, and tested for complementation. TPS1 protein localized predominantly in the phloem-loading zone and guard cells in leaves, root vasculature, and shoot apical meristem, implicating it in both local and systemic signaling of Suc status. The protein is targeted mainly to the nucleus. Restoring Tre6P synthesis was both necessary and sufficient to rescue the tps1-1 mutant through embryogenesis. However, postembryonic growth and the sucrose-Tre6P relationship were disrupted in some complementation lines. A point mutation (A119W) in the catalytic domain or truncating the C-terminal domain of TPS1 severely compromised growth. Despite having high Tre6P levels, these plants never flowered, possibly because Tre6P signaling was disrupted by two unidentified disaccharide-monophosphates that appeared in these plants. The noncatalytic domains of TPS1 ensure its targeting to the correct subcellular compartment and its catalytic fidelity and are required for appropriate signaling of Suc status by Tre6P.
Impact of Asparaginase Discontinuation on Outcome in Childhood Acute Lymphoblastic Leukemia: A Report From the Children's Oncology Group.

PURPOSE Asparaginase (ASNase) is an important component of acute lymphoblastic leukemia (ALL) treatment, but is often discontinued because of toxicity. Erwinia chrysanthemi ASNase (Erwinia) substitution was approved in 2011 for allergic reactions. Erwinia has, however, been intermittently unavailable because of drug supply issues. The impact of Erwinia substitution or complete ASNase discontinuation is unknown. METHODS Patients aged 1-30.99 years in frontline Children's Oncology Group trials for B-cell acute lymphoblastic leukemia between 2004 and 2011 (National Cancer Institute [NCI] standard risk [SR]: AALL0331; NCI high risk: AALL0232) were included. The number of prescribed pegaspargase (PEG-ASNase) doses varied by trial and strata. Maintenance therapy did not contain ASNase. Landmark analyses at maintenance compared disease-free survival (DFS) among those receiving all prescribed PEG-ASNase doses versus switching to Erwinia but receiving all doses versus not receiving all ASNase doses. RESULTS We included 5,195 AALL0331 and 3,001 AALL0232 patients. The cumulative incidence of PEG-ASNase discontinuation was 12.2% ± 4.6% in AALL0331 and 25.4% ± 0.8% in AALL0232. In multivariable analyses, NCI high-risk patients not receiving all prescribed ASNase doses had inferior DFS (hazard ratio [HR], 1.5; 95% CI, 1.2 to 1.9; P = .002) compared with those receiving all prescribed PEG-ASNase doses. Patients with Erwinia substitution who completed subsequent courses were not at increased risk (HR, 1.1; 95% CI, 0.7 to 1.6; P = .69). NCI SR patients who discontinued ASNase were not at elevated risk (HR, 1.2; 95% CI, 0.9 to 1.6; P = .23), except when restricted to those with slow early response, who were prescribed more ASNase because of therapy intensification (HR, 1.7; 95% CI, 1.1 to 2.7; P = .03). CONCLUSION Discontinuation of ASNase doses is associated with inferior DFS in higher-risk patients. Our results illustrate the severe consequences of Erwinia shortages.
Dysregulation of humoral immunity in chronic infection

Chronic viral infections disrupt the ability of the humoral immune response to produce neutralizing antibody or form effective immune memory, preventing viral clearance and making vaccine design difficult. Multiple components of the B‐cell response are affected by pathogens that are not cleared from the host. Changes in the microenvironment shift production of B cells to short‐lived plasma cells early in the response. Polyclonal B cells are recruited into both the plasma cell and germinal center compartments, inhibiting the formation of a targeted, high‐affinity response. Finally, memory B cells shift toward an “atypical” phenotype, which may in turn result in changes to the functional properties of this population. While similar properties of B‐cell dysregulation have been described across different types of persistent infections, key questions about the underlying mechanisms remain. This review will discuss the recent advances in this field, as well as highlight the critical questions about the interplay between viral load, microenvironment, the polyclonal response and atypical memory B cells that are yet to be answered. Design of new preventative treatments will rely on identifying the extrinsic and intrinsic modulators that push B cells toward an ineffective response, and thus identify new ways to guide them back onto the best path for clearance of virus and formation of effective immune memory.
The metabolic response to inflammation in astrocytes is regulated by nuclear factor‐kappa B signaling

Inflammation and metabolism are intrinsically linked with inflammatory stimuli inducing metabolic changes in cells and, in turn, metabolic capacity determining cellular inflammatory responses. Although well characterized in peripheral immune cells there is comparatively less known about these “immunometabolic” responses in astrocytes. In this study, we tested the hypothesis that the astrocytic inflammatory response driven by nuclear factor‐kappa B (NF‐κB) signaling is dependent on glycolytic metabolism. Using mouse primary cortical astrocyte cultures, we assessed changes in cellular metabolism after exposure to lipopolysaccharide (LPS), with cytokine ELISAs and immunoblotting being used to measure inflammatory responses. Results indicate temporally distinct metabolic adaptations to pro‐inflammatory stimulation in astrocytes: 3 hr LPS treatment increased glycolysis but did not alter mitochondrial metabolism, while following 24 hr of LPS treatment we observed increased oxidative phosphorylation, and decreased glycolytic capacity and glucose uptake, partly due to reduced glucose transporter 1 expression. Inhibition of NF‐κB signaling with the IKK‐beta inhibitor TPCA‐1 prevented the LPS induced changes to glycolysis and oxidative phosphorylation. Furthermore, TPCA‐1 treatment altered both glycolysis and oxidative phosphorylation independently from inflammatory stimulation, indicating a role for NF‐κB signaling in regulation of basal metabolism in astrocytes. Inhibition of glycolysis with 2‐deoxyglucose significantly attenuated LPS‐induced cytokine release and NF‐κB phosphorylation, indicating that intact glycolysis is required for the full inflammatory response to LPS. Together our data indicate that astrocytes display immunometabolic responses to acute LPS stimulation which may represent a potential therapeutic target for neuroinflammatory disorders.