Miracle-dz/UniFAR-FTUs huggingface dataset:
Dynamic Constitutional Frameworks as antibacterial and antibiofilm agents.

Dynamic Constitutional Frameworks (DCFs) were synthesized and screened for biofilm inhibition or disruption. They are composed of a trialdehyde core reversibly linked to a diamine PEG connector and to a variety of neutral, anionic or cationic heads, to generate a library of DCFs to generate multivalent dendritic architectures in the presence of Pseudomonas aeruginosa and Staphylococcus aureus. The best DCFs were always polycationic and the nature of the cationic heads significantly impact the antibiofilm activity. The best antibiofilm activity was observed for DCF3B, displaying a polyethyleneimine head. Interestingly, a simple inactive guanidinium functional head, strongly inhibited biofilm growth when assayed as a multivalent DCF3C. Using a more advanced in vitro bioﬁlm model of chronic wound infection, DCF3C was found significantly superior than all other DCFs. These results demonstrate 1) the versatility and effectiveness of DCFs as low cost and efficient systems for antibiofilm disruption 2) the efficiency of dynamic chemistry as a discovery technology.
Conserved immunogenic peptides of Ebola glycoprotein elicit immune response in human peripheral blood mononuclear cells

In the past 45 years, ebolaviruses have periodically caused epidemics on the African continent. In December 2019, approval of a recombinant vector‐based EBOV vaccine, named Ervebo, came as encouraging news; still, there is a long way to go in the development of an accessible, global, and pan‐ebolavirus vaccine. The current study expanded our previous in silico work which was conducted on ebolavirus glycoprotein and this resulted in the identification of three potentially immunogenic peptides (P1 – FKRTSFFLWVIILFQRTFSIPL, P2 – LANETTQALQLF, and P3 – RATTELRTFSILNRKAIDF). An analysis to estimate the number of expected human leukocyte antigen (HLA) responders revealed that P1, P2, and P3 can potentially interact with 2540, 2150, and 2802 HLA alleles, respectively. Further, these peptides were subject to in vitro analysis wherein the human peripheral blood mononuclear cell proliferation and interferon‐gamma (IFN‐γ) production by peptide stimulated cells was studied in 10 healthy human blood samples with the help of a 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyl tetrazolium bromide (MTT) assay and a sandwich enzyme‐linked immunosorbent assay (ELISA) respectively. P3 presented the best results, a significant (P < 0.05) peptide induced cell proliferation and IFN‐γ stimulation for 8 and 10 samples, respectively, followed by P1 (5 and 6) and P2 (5 and 7). The in silico and in vitro results obtained in this study indicate the immunogenic potential of these peptides and warrant exploration of the effects on other cytokines as well as in vivo experimental validation.
Characterization and Ex Vivo evaluation of an extracorporeal high‐intensity focused ultrasound (HIFU) system

Abstract Background High‐intensity focused ultrasound (HIFU) has been in clinical use for a variety of solid tumors and cancers. Accurate and reliable calibration is in a great need for clinical applications. An extracorporeal clinical HIFU system applied for the investigational device exemption (IDE) to the Food and Drug Administration (FDA) so that evaluation of its characteristics, performance, and safety was required. Methods The acoustic pressure and power output was characterized by a fiber optic probe and a radiation force balance, respectively, with the electrical power up to 2000 W. An in situ acoustic energy was established as the clinical protocol at the electrical power up to 500 W. Temperature elevation inside the tissue sample was measured by a thermocouple array. Generated lesion volume at different in situ acoustic energies and pathological examination of the lesions was evaluated ex vivo. Results Acoustic pressure mapping showed the insignificant presence of side/grating lobes and pre‐ or post‐focal peaks (≤−12 dB). Although distorted acoustic pressure waveform was found in the free field, the nonlinearity was reduced significantly after the beam propagating through tissue samples (i.e., the second harmonic of −11.8 dB at 500 W). Temperature elevation was <10°C at a distance of 10 mm away from a 20‐mm target, which suggests the well‐controlled HIFU energy deposition and no damage to the surrounding tissue. An acoustic energy in the range of 750–1250 J resulted in discrete lesions with an interval space of 5 mm between the treatment spots. Histology confirmed that the lesions represented a region of permanently damaged cells by heat fixation, without causing cell lysis by either cavitation or boiling. Conclusions Our characterization and ex vivo evaluation protocol met the IDE requirement. The in‐situ acoustic energy model will be used in clinical trials to deliver almost consistent energy to the various targets.
Neue Entwicklungen und Perspektiven in der Akromegalie

Was ist neu? Diagnostik Bei Verdacht auf eine Akromegalie wird zunächst das Hormon Insulin-like growth factor 1 (IGF-1) als wesentlicher Mediator des Wachstumshormons (GH) bestimmt. Ist es erhöht, schließt sich eine Bestätigungsdiagnostik mittels GH-Suppressionstest an. Neue Arbeiten empfehlen für diesen Test niedrigere GH-Grenzwerte als früher, zudem sollen potenzielle Einflussgrößen (z. B. Body-Mass-Index) stärker berücksichtigt werden. Perspektivisch könnten Erkrankte mittels einer automatisierten Gesichtserkennung ggf. leichter identifiziert werden. Komorbiditäten Bei einem unkontrollierten GH-Exzess sind Lebensqualität und -erwartung zum Teil erheblich reduziert. Eine Akromegalie sowie deren typische Folgeerkrankungen (z. B. Schlafapnoe, Kardiomyopathie, Arthropathie) müssen daher frühzeitig erkannt werden. Kürzlich wurden neue Empfehlungen für ein standardisiertes diagnostisches Vorgehen publiziert. Therapie Die operative Adenomentfernung durch einen erfahrenen Hypophysenchirurgen ist Therapie der Wahl. Bei residueller Erkrankung kann perspektivisch eine Kombination aus volumetrischer Magnetresonanztomografie (MRT) und 11C-Methionin-Positronen-Emissions-Tomografie (PET) eine Folgeoperation erleichtern. Für die typische Zweitlinientherapie mit Somatostatin-Analoga (SSA) ist nun erstmals auch ein oral einzusetzendes Präparat verfügbar. Neue Daten belegen die Wirksamkeit und Sicherheit einer Hypophysenbestrahlung. Spezielle Patientenpopulationen Schwangere und ältere Patienten bedürfen besonderer Aufmerksamkeit. Gemäß aktueller Daten wirkt sich die COVID-Pandemie auch bei einer Akromegalie nachteilig auf Diagnostik und Therapie aus.
Hepatotoxicity of food-borne mycotoxins: molecular mechanism, anti-hepatotoxic medicines and target prediction

Abstract Mycotoxins are metabolites produced by fungi. The widespread contamination of food and feed by mycotoxins is a global food safety problem and a serious threat to people’s health. Most food-borne mycotoxins have strong hepatotoxicity. However, no effective methods have been found to prevent or treat Mycotoxin- Induced Liver Injury (MILI) in clinical and animal husbandry. In this paper, the molecular mechanisms and potential anti-MILI medicines of six food-borne MILI are reviewed, and their targets are predicted by network toxicology, which provides a theoretical basis for further study of the toxicity mechanism of MILI and the development of effective strategies to manage MILI-related health problems in the future and accelerate the development of food safety.
Unsupervised Feature Selection With Weighted and Projected Adaptive Neighbors

In the field of data mining, how to deal with high-dimensional data is a fundamental problem. If they are used directly, it is not only computationally expensive but also difficult to obtain satisfactory results. Unsupervised feature selection is designed to reduce the dimension of data by finding a subset of features in the absence of labels. Many unsupervised methods perform feature selection by exploring spectral analysis and manifold learning, such that the intrinsic structure of data can be preserved. However, most of these methods ignore a fact: due to the existence of noise features, the intrinsic structure directly built from original data may be unreliable. To solve this problem, a new unsupervised feature selection model is proposed. The graph structure, feature weights, and projection matrix are learned simultaneously, such that the intrinsic structure is constructed by the data that have been feature weighted and projected. For each data point, its nearest neighbors are acquired in the process of graph construction. Therefore, we call them adaptive neighbors. Besides, an additional constraint is added to the proposed model. It requires that a graph, corresponding to a similarity matrix, should contain exactly $c$ connected components. Then, we present an optimization algorithm to solve the proposed model. Next, we discuss the method of determining the regularization parameter $\gamma $ in our proposed method and analyze the computational complexity of the optimization algorithm. Finally, experiments are implemented on both synthetic and real-world datasets to demonstrate the effectiveness of the proposed method.
Measurement invariance of the Childhood Autism Rating Scale (CARS) across six countries

The Childhood Autism Rating Scale (CARS) is a simple and inexpensive tool for Autism spectrum disorder (ASD) assessments, with evidenced psychometric data from different countries. However, it is still unclear whether ASD symptoms are measured the same way across different societies and world regions with this tool, since data on its cross‐cultural validity are lacking. This study evaluated the cross‐cultural measurement invariance of the CARS among children with ASD from six countries, for whom data were aggregated from previous studies in India (n = 101), Jamaica (n = 139), Mexico (n = 72), Spain (n = 99), Turkey (n = 150), and the United States of America (n = 186). We analyzed the approximate measurement invariance based on Bayesian structural equation modeling. The model did not fit the data and its measurement invariance did not hold, with all items found non‐invariant across the countries. Items related to social communication and interaction (i.e., relating to people, imitation, emotional response, and verbal and nonverbal communication) displayed lower levels of cross‐country non‐invariance compared to items about stereotyped behaviors/sensory sensitivity (i.e., body and object use, adaptation to change, or taste, smell, and touch response). This study found that the CARS may not provide cross‐culturally valid ASD assessments. Thus, cross‐cultural comparisons with the CARS should consider first which items operate differently across samples of interest, since its cross‐cultural measurement non‐invariance could be a source of cross‐cultural variability in ASD presentations. Additional studies are needed before drawing valid recommendations in relation to the cultural sensitivity of particular items.
Clinical evidence for a biological effect of epigenetically active decitabine in relapsed or progressive rhabdoid tumors

Refined therapy has helped to improve survival rates in rhabdoid tumors (RT). Prognosis for patients with chemoresistant, recurrent, or progressive RT remains dismal. Although decitabine, an epigenetically active agent, has mainly been evaluated in the management of hematologic malignancies in adults, safety in children has also been demonstrated repeatedly.
Improving the Quality of Inpatient Discharge Instructions: An Evaluation and Implementation of Best Practices

Written discharge instructions for patients are an important part of the discharge process. They often do not contain information that is useful for patients once they leave the hospital, however. The authors show that sequential interventions, including educational outreach and redesigned templates, were successful in improving the quality of patient discharge instructions. Abstract Objectives Little is known about whether improving the quality of written discharge instructions can result in improved readmission rates and whether there are differences in the quality of discharge instructions based on provider and patient characteristics. We set out to determine provider characteristics associated with high quality discharge instructions and whether redesigned discharge instructions would lead to improvement in their quality and reduce hospital readmission rates. Methods We instituted sequential interventions of educational outreach and a redesigned discharge instructions template and evaluated their quality using 11 metrics based on established best practices and subsequent 30-day readmission rates. Results In total, 225 randomly selected charts were reviewed during a 15-month period. An average of 5.36 quality metrics were completed before our interventions, which increased to 5.61 after educational outreach and 7.16 after the template was redesigned. The risk standardized 30-day readmission rate fluctuated from a baseline of 10.48% to 12.71% and 10.97% following each intervention, respectively. Medical students completed significantly more quality metrics than interns, residents, or attendings (P < 0.05 for all) and residents completed significantly more than attendings (P = 0.014). Conclusions Although an education intervention was ineffective in improving discharge instruction quality, a redesigned discharge instructions template did improve the quality of patient discharge instructions. Neither intervention led to a meaningful change in readmission rates. We also found significant differences in the quality of discharge instructions based on the level of training of the author of the discharge instructions.
Risk of suicide in patients who present to hospital after self-cutting according to site of injury: findings from the Multicentre Study of Self-harm in England

Abstract Background We compared the risk of death by suicide following hospital presentation for self-harm according to site of self-cut/stab. Method We included 54 999 self-harm presentations (involving 31 419 individuals) to hospitals in the Multicentre Study of Self-harm in England (1/1/2004–31/12/2014), with mortality follow-up to 31/12/2019. Information on method of self-harm was obtained through monitoring in hospitals. Information about mortality was obtained through linkage with NHS Digital. We assessed the association of site of self-cut with death by suicide using mixed effect models. Results In total, 10 790 (19.6%) hospital presentations involved self-cutting/stabbing, 7489 of which (69.4%) were due to laceration to the arm/wrist alone, 1846 episodes (17.1%) involved cutting elsewhere on the body, and 1455 (13.5%) were due to laceration to unknown site. Controlling for confounders, presentation to a hospital following self-cut/stab to bodily parts other than wrist/arm was associated with greater chance of subsequent suicide relative to presentation after self-poisoning alone [adjusted odds ratio (aOR) 1.75, 95% confidence interval (CI) 1.03–2.96, p = 0.038]. The likelihood of suicide after presentation for cutting/stabbing the wrist/arm alone was comparable to that of patients who had self-poisoned alone. Presentations after laceration involving the neck were associated with a four-fold greater chance of subsequent suicide relative to self-poisoning (aOR 4.09, 95% CI 1.80–9.30, p = 0.001). Conclusions Patients who attend hospital after self-cutting/stabbing are a heterogeneous group in terms of characteristics, methods of cutting/stabbing and risk of subsequent suicide. Risk of suicide is greater in individuals who self-cut/stab to parts of the body other than the wrist or arm, especially the neck.
The legacy of george olah

The life of George Olah exemplifies the fate of Hungarian scientific excellence in the 20th century. He was talented and a hard worker, but he could not remain in his country and had to seek a new life in the West. His life-long scientific interests developed in the Budapest Technical University helped him to overcome obstacles and he became a leading chemist of worldwide fame. His qualities and flexibility in both scientific research and practical applications serve as a brilliant example for generations to come.
Quantitative developmental biology in vitro using micropatterning

ABSTRACT Micropatterning encompasses a set of methods aimed at precisely controlling the spatial distribution of molecules onto the surface of materials. Biologists have borrowed the idea and adapted these methods, originally developed for electronics, to impose physical constraints on biological systems with the aim of addressing fundamental questions across biological scales from molecules to multicellular systems. Here, I approach this topic from a developmental biologist's perspective focusing specifically on how and why micropatterning has gained in popularity within the developmental biology community in recent years. Overall, this Primer provides a concise overview of how micropatterns are used to study developmental processes and emphasises how micropatterns are a useful addition to the developmental biologist’s toolbox.
Counterfactual mediation analysis in the multistate model framework for surrogate and clinical time‐to‐event outcomes in randomized controlled trials

In cancer randomized controlled trials, surrogate endpoints are frequently time‐to‐event endpoints, subject to the competing risk from the time‐to‐event clinical outcome. In this context, we introduce a counterfactual‐based mediation analysis for a causal assessment of surrogacy. We use a multistate model for risk prediction to account for both direct transitions towards the clinical outcome and indirect transitions through the surrogate outcome. Within the counterfactual framework, we define natural direct and indirect effects with a causal interpretation. Based on these measures, we define the proportion of the treatment effect on the clinical outcome mediated by the surrogate outcome. We estimate the proportion for both the cumulative risk and restricted mean time lost. We illustrate our approach by using 18‐year follow‐up data from the SPCG‐4 randomized trial of radical prostatectomy for prostate cancer. We assess time to metastasis as a surrogate outcome for prostate cancer‐specific mortality.
Regulatory T cell deficiency in patients with eosinophilic asthma

Abstract Background: There is a lack of information about regulatory T cells (Tregs) and inflammatory phenotypes in patients with asthma. In this study, we aimed to compare the characteristics of Tregs in patients with eosinophilic asthma.Methods: Forty healthy and 120 stable asthmatic patients were recruited. Sputum and airway inflammatory phenotypes were assessed, and all patients were followed for one year. Human peripheral blood mononuclear cells (PBMCs) were collected and stimulated with phytohemagglutinin (PHA) and Dermatophagoides farina (Derp) to detect CD4+CD25+FOXP3+T cells and Foxp3 levels. Interleukin (IL)-13, IL-5, IL-17, IL-9, and interferon (IFN)-γ levels were measured.Results: 38.33% of patients had eosinophilic asthma, 13.33% had neutrophilic asthma, 6.67% had mixed granulocytic asthma, and 41.67% had pauci-granulocytic asthma. The eosinophilic asthma patients had a relatively high Asthma Control Test (ACT) score, an increased prediction and improvement FEV1 (%) rate, and elevated total IgE serum levels (P < 0.05). T helper cell 2 (Th2) cytokines IL-13 and IL-5 were predominantly expressed in the eosinophilic phenotype, while the Th1 cytokine IFN-γ and Th17 cytokine were found in the neutrophilic phenotype. IL-10 was significantly lower in eosinophilic asthmatic patients compared to the controls (P < 0.05). CD4+CD25+FOXP3+T cells (%Tregs) and Foxp3 gene expression in the PHA stimulated eosinophilic asthma samples were significantly lower compared to the control samples (P < 0.05). The airway inflammation phenotypes remained stable after one-year of therapy.Conclusion: Asthmatic patients with the eosinophilic phenotype in this study were deficient in Tregs, as characterized by a Th2 cell-biased pattern.
Plasmon-exciton interaction in the thin film of inhomogeneous ensemble of silver nanoparticles and cyanine J-aggregates

The optical properties of organometallic films of silver nanoparticles and J-aggregates of pseudoisocyanine dye have been studied to observation of the plasmon-exciton interaction. The original method for obtaining J-aggregates on inhomogeneous island silver films without use of salt and water was developed. Owing to the broad bandwidth of inhomogeneous plasmon resonances; it is possible to study the interaction of nanoparticles and J-aggregates, obtained in the spin-coated layer on the silver island film. The absorption spectrum of the organometallic film is not a simple sum of the spectra composing its components. The absorption of dye molecules increases several times in the presence of silver nanoparticles, which is due to the influence of the near fields of the latter. The spectral dip in the absorption maximum of the J-aggregate of pseudoisocyanine was observed; it became more symmetrical with an increasing equivalent thickness of the island film.
OsMADS23 phosphorylated by SAPK9 confers drought and salt tolerance by regulating ABA biosynthesis in rice

Some of MADS-box transcription factors (TFs) have been shown to play essential roles in the adaptation of plant to abiotic stress. Still, the mechanisms that MADS-box proteins regulate plant stress response are not fully understood. Here, a stress-responsive MADS-box TF OsMADS23 from rice conferring the osmotic stress tolerance in plants is reported. Overexpression of OsMADS23 remarkably enhanced, but knockout of the gene greatly reduced the drought and salt tolerance in rice plants. Further, OsMADS23 was shown to promote the biosynthesis of endogenous ABA and proline by activating the transcription of target genes OsNCED2, OsNCED3, OsNCED4 and OsP5CR that are key components for ABA and proline biosynthesis, respectively. Then, the convincing evidence showed that the OsNCED2-knockout mutants had lower ABA levels and exhibited higher sensitivity to drought and oxidative stress than wild type, which is similar to osmads23 mutant. Interestingly, the SnRK2-type protein kinase SAPK9 was found to physically interact with and phosphorylate OsMADS23, and thus increase its stability and transcriptional activity. Furthermore, the activation of OsMADS23 by SAPK9-mediated phosphorylation is dependent on ABA in plants. Collectively, these findings establish a mechanism that OsMADS23 functions as a positive regulator in response to osmotic stress by regulating ABA biosynthesis, and provide a new strategy for improving drought and salt tolerance in rice.
Surviving an Extensive Burn Injury Using Advanced Skin Replacement Technologies.

There have been significant improvements in the technology available for treating extensive burns in the past decade. This case presents two unique, skin replacement technologies that were used to treat an 86% surface area flame burn in a pediatric patient. A temporary dermal replacement, known as "Novosorb™ Biodegradable Temporizing Matrix" was first used to stabilize the burn injury and remained in place for approximately three months. Given the large burn size and lack of available donor skin for grafting, a permanent skin replacement product known as "Self-Assembled Skin Substitute (SASS)" was then utilized to cover the burns. SASS is a novel technology that was developed to replace skin as an autologous skin graft and is currently available in Canada through a clinical trial for major burns. Ultimately, the concurrent use of these two technologies allowed for the unprecedented survival of a child following an extensive and life-threatening burn injury.