Miracle-dz/UniFAR-FTUs huggingface dataset:
Sustainable Aromatic Aliphatic Polyesters and Polyurethanes Prepared from Vanillin-Derived Diols via Green Catalysis

The design and preparation of polymers by using biobased chemicals is regarded as an important strategy towards a sustainable polymer chemistry. Herein, two aromatic diols, 4-(hydroxymethyl)-2-methoxyphenol and 2-(4-(hydroxymethyl)-2-methoxyphenoxy)ethanol, have been prepared in good yields through the direct reduction of vanillin and hydroxyethylated vanillin (4-(2-hydroxyethoxy)-3-methoxybenzaldehyde) using NaBH4, respectively. The diols were submitted to traditional polycondensation and polyaddition with acyl chlorides and diisocyanatos, and serials of new polyesters and polyurethanes were prepared in high yields with moderate molecular weight ranging from 17,000 to 40,000 g mol−1. Their structures were characterized by 1H NMR, 13C NMR and FTIR, and their thermal properties were studied by TGA and differential scanning calorimetry (DSC), indicating that the as-prepared polyesters and polyurethanes have Tg in the range of 16.2 to 81.2 °C and 11.6 to 80.4 °C, respectively.
Opipramol Inhibits Lipolysis in Human Adipocytes without Altering Glucose Uptake and Differently from Antipsychotic and Antidepressant Drugs with Adverse Effects on Body Weight Control

Treatment with several antipsychotic drugs exhibits a tendency to induce weight gain and diabetic complications. The proposed mechanisms by which the atypical antipsychotic drug olanzapine increases body weight include central dysregulations leading to hyperphagia and direct peripheral impairment of fat cell lipolysis. Several investigations have reproduced in vitro direct actions of antipsychotics on rodent adipocytes, cultured preadipocytes, or human adipose tissue-derived stem cells. However, to our knowledge, no such direct action has been described in human mature adipocytes. The aim of the present study was to compare in human adipocytes the putative direct alterations of lipolysis by antipsychotics (haloperidol, olanzapine, ziprazidone, risperidone), antidepressants (pargyline, phenelzine), or anxiolytics (opipramol). Lipolytic responses to the tested drugs, and to recognized lipolytic (e.g., isoprenaline) or antilipolytic agents (e.g., insulin) were determined, together with glucose transport and amine oxidase activities in abdominal subcutaneous adipocytes from individuals undergoing plastic surgery. None of the tested drugs were lipolytic. Surprisingly, only opipramol exhibited substantial antilipolytic properties in the micromolar to millimolar range. An opipramol antilipolytic effect was evident against isoprenaline-, forskolin-, or atrial natriuretic peptide-stimulated lipolysis. Opipramol did not impair insulin activation of glucose transport but inhibited monoamine oxidase (MAO) activity to the same extent as antidepressants recognized as MAO inhibitors (pargyline, harmine, or phenelzine), whereas antipsychotics were inefficient. Considering its unique properties, opipramol, which is not associated with weight gain in treated patients, is a good candidate for drug repurposing because it limits exaggerated lipolysis, prevents hydrogen peroxide release by amine oxidases in adipocytes, and is thereby of potential use to limit lipotoxicity and oxidative stress, two deleterious complications of diabetes and obesity.
Health Literacy as Communicative Action—A Qualitative Study among Persons at Risk in the Context of Predictive and Preventive Medicine

Predictive and preventive medicine play an increasingly important role in public debates on health, providing cutting-edge technologies with the potential to measure and predict individual risks of getting ill. This leads to an ever-expanding definitional space between being “healthy” and being “ill”, challenging the individual’s everyday life, attitudes and perceptions towards the self and the process of health-related decision-making. “How do the condition of ‘being at risk’ and individual health literacy interrelate? ” is the leading question of the current contribution. Drawing on empirical qualitative data, collected by means of narrative interviews with persons at risk in four clinical fields, a bottom-up ethnographic and health sciences perspective on health literacy (with an emphasis on critical health literacy) is employed. The findings will be embedded within theoretical approaches dealing with power relations and communication in healthcare encounters, particularly Habermas’ theory of communicative action. The core outcome of our study is a concept for an overarching model of health literacy in the context of health-related risk prediction across indications, based on empirical insights gained through interpretative analysis of the four clinical domains.
The HIV-1 capsid-binding host factor CPSF6 is post-transcriptionally regulated by the cellular microRNA miR-125b

Cleavage and polyadenylation specificity factor 6 (CPSF6) is a cellular protein involved in mRNA processing. Emerging evidence suggests that CPSF6 also plays key roles in HIV-1 infection, specifically during nuclear import and integration targeting. However, the cellular and molecular mechanisms that regulate CPSF6 expression are largely unknown. In this study, we report a post-transcriptional mechanism that regulates CPSF6 via the cellular microRNA miR-125b. An in silico analysis revealed that the 3′UTR of CPSF6 contains a miR-125b–binding site that is conserved across several mammalian species. Because miRNAs repress protein expression, we tested the effects of miR-125b expression on CPSF6 levels in miR-125b knockdown and over-expression experiments, revealing that miR-125b and CPSF6 levels are inversely correlated. To determine whether miR-125b post-transcriptionally regulates CPSF6, we introduced the 3′UTR of CPSF6 mRNA into a luciferase reporter and found that miR-125b negatively regulates CPSF6 3′UTR-driven luciferase activity. Accordingly, mutations in the miR-125b seed sequence abrogated the regulatory effect of the miRNA on the CPSF6 3′UTR. Finally, pulldown experiments demonstrated that miR-125b physically interacts with CPSF6 3′UTR. Interestingly, HIV-1 infection down-regulated miR-125b expression concurrent with up-regulation of CPSF6. Notably, miR-125b down-regulation in infected cells was not due to reduced pri-miRNA or pre-miRNA levels. However, miR-125b down-regulation depended on HIV-1 reverse transcription but not viral DNA integration. These findings establish a post-transcriptional mechanism that controls CPSF6 expression and highlight a novel function of miR-125b during HIV-host interaction.
Cardiac Remodeling in Chronic Kidney Disease

Cardiac remodeling occurs frequently in chronic kidney disease patients and affects quality of life and survival. Current treatment options are highly inadequate. As kidney function declines, numerous metabolic pathways are disturbed. Kidney and heart functions are highly connected by organ crosstalk. Among others, altered volume and pressure status, ischemia, accelerated atherosclerosis and arteriosclerosis, disturbed mineral metabolism, renal anemia, activation of the renin-angiotensin system, uremic toxins, oxidative stress and upregulation of cytokines stress the sensitive interplay between different cardiac cell types. The fatal consequences are left-ventricular hypertrophy, fibrosis and capillary rarefaction, which lead to systolic and/or diastolic left-ventricular failure. Furthermore, fibrosis triggers electric instability and sudden cardiac death. This review focuses on established and potential pathophysiological cardiorenal crosstalk mechanisms that drive uremia-induced senescence and disease progression, including potential known targets and animal models that might help us to better understand the disease and to identify novel therapeutics.
Microglial depletion disrupts normal functional development of adult-born neurons in the olfactory bulb

Microglia play key roles in regulating synapse development and refinement in the developing brain, but it is unknown whether they are similarly involved during adult neurogenesis. By transiently depleting microglia from the healthy adult mouse brain, we show that microglia are necessary for the normal functional development of adult-born granule cells (abGCs) in the olfactory bulb. Microglial depletion reduces the odor responses of developing, but not preexisting GCs in vivo in both awake and anesthetized mice. Microglia preferentially target their motile processes to interact with mushroom spines on abGCs, and when microglia are absent, abGCs develop smaller spines and receive weaker excitatory synaptic inputs. These results suggest that microglia promote the development of excitatory synapses onto developing abGCs, which may impact the function of these cells in the olfactory circuit.
Integrated Transcriptomic and Un-Targeted Metabolomics Analysis Reveals Mulberry Fruit (Morus atropurpurea) in Response to Sclerotiniose Pathogen Ciboria shiraiana Infection

Mulberry sclerotiniose caused by Ciboria shiraiana is a devastating disease of mulberry (Morus alba L.) fruit in Northwest China. At present, no disease-resistant varieties are used in production, as the molecular mechanisms of this disease are not well understood. In this study, to explore new prevention methods and provide direction for molecular breeding, transcriptomic sequencing and un-targeted metabolomics were performed on healthy (CK), early-stage diseased (HB1), and middle-stage diseased (HB2) mulberry fruits. Functional annotation, gene ontology, a Kyoto encyclopedia of genes and genomes (KEGG) analysis, and a Mapman analysis of the differentially expressed genes revealed differential regulation of genes related to plant hormone signal transduction, transcription factors, and phenylpropanoid biosynthesis. A correspondence between the transcript pattern and metabolite profile was observed in the phenylpropanoid biosynthesis pathway. It should be noted that the log2 ratio of eugenol (isoeugenol) in HB1 and HB2 are 85 times and 23 times higher than CK, respectively. Our study shows that phenylpropanoid biosynthesis may play an essential role in response to sclerotiniose pathogen infection and eugenol(isoeugenol) enrichment in mulberry fruit, which may provide a novel method for mulberry sclerotiniose control.
Longitudinal dynamics of the human B cell response to the yellow fever 17D vaccine

Significance The yellow fever virus 17D (YFV-17D) vaccine is one of the safest and most effective vaccines ever developed and is widely considered to be the “gold standard” of antiviral vaccination. Despite its success, remarkably little is known about the human B cell response induced by YFV-17D and the specificities and functional activities of the antibodies encoded by these B cells. Here we report the molecular characterization of the complexity, dynamics, and evolution of this response at the single-cell level. Our work provides key insights into the B cell response underlying the efficacy of the YFV-17D vaccine, which may facilitate the design of vaccines for more refractory pathogens, such as malaria and HIV. A comprehensive understanding of the development and evolution of human B cell responses induced by pathogen exposure will facilitate the design of next-generation vaccines. Here, we utilized a high-throughput single B cell cloning technology to longitudinally track the human B cell response to the yellow fever virus 17D (YFV-17D) vaccine. The early memory B cell (MBC) response was mediated by both classical immunoglobulin M (IgM) (IgM+CD27+) and switched immunoglobulin (swIg+) MBC populations; however, classical IgM MBCs waned rapidly, whereas swIg+ and atypical IgM+ and IgD+ MBCs were stable over time. Affinity maturation continued for 6 to 9 mo following vaccination, providing evidence for the persistence of germinal center activity long after the period of active viral replication in peripheral blood. Finally, a substantial fraction of the neutralizing antibody response was mediated by public clones that recognize a fusion loop-proximal antigenic site within domain II of the viral envelope glycoprotein. Overall, our findings provide a framework for understanding the dynamics and complexity of human B cell responses elicited by infection and vaccination.
Protein Kinase C subtype δ interacts with Venezuelan equine encephalitis virus capsid protein and regulates viral RNA binding through modulation of capsid phosphorylation

Protein phosphorylation plays an important role during the life cycle of many viruses. Venezuelan equine encephalitis virus (VEEV) capsid protein has recently been shown to be phosphorylated at four residues. Here those studies are extended to determine the kinase responsible for phosphorylation and the importance of capsid phosphorylation during the viral life cycle. Phosphorylation site prediction software suggests that Protein Kinase C (PKC) is responsible for phosphorylation of VEEV capsid. VEEV capsid co-immunoprecipitated with PKCδ, but not other PKC isoforms and siRNA knockdown of PKCδ caused a decrease in viral replication. Furthermore, knockdown of PKCδ by siRNA decreased capsid phosphorylation. A virus with capsid phosphorylation sites mutated to alanine (VEEV CPD) displayed a lower genomic copy to pfu ratio than the parental virus; suggesting more efficient viral assembly and more infectious particles being released. RNA:capsid binding was significantly increased in the mutant virus, confirming these results. Finally, VEEV CPD is attenuated in a mouse model of infection, with mice showing increased survival and decreased clinical signs as compared to mice infected with the parental virus. Collectively our data support a model in which PKCδ mediated capsid phosphorylation regulates viral RNA binding and assembly, significantly impacting viral pathogenesis.
‘French LARS score’: validation of the French version of the low anterior resection syndrome (LARS) score for measuring bowel dysfunction after sphincter-preserving surgery among rectal cancer patients: a study protocol

Introduction Many bowel problems following low anterior resection (LAR) for rectal cancer considerably impair the quality of life (QoL) of patients. The LAR syndrome (LARS) scale is a self-report questionnaire to identify and assess bowel dysfunction after rectal cancer surgery. It has been translated and validated in several languages but not in French (metropolitan French). The primary objective is to adapt the LARS scale to the French language (called French-LARS score) and to assess its psychometric properties. Secondary objectives are to assess both the prevalence and severity of LARS and to measure their impact on QoL. Methods and analysis A French multicentre observational cohort study has been designed. The validation study will include translation of the LARS scale following the current international recommendations, assessment of its reliability, convergent and discriminant validities, sensitivity, internal consistency, internal validity and confirmatory analyses. One thousand patients will be enrolled for the analyses. The questionnaire will be initially administered to the first 100 patients to verify the adequacy and degree of comprehension of the questions. Then reproducibility will be investigated by a test–retest procedure in the following 400 patients. An analysis will be conducted to determine the correlation between the LARS score and the Quality of Life Questionnaire (QLQ; European Organization for Treatment and Research of Cancer’s QLQ-C30, QLQ-CR29). Risk factors linked to QoL deterioration will be identified and their impact will be measured. This study will meet the need for a validated tool to improve patient care and QoL. Ethics and dissemination The institutional review board of the University Hospital of Caen and the ethics committee (CPP Nord Ouest I, 25 January 2019) approved the study. Trial registration number NCT03569488.
Extracorporeal life support after failure of thrombolysis in pulmonary embolism.

INTRODUCTION Fulminant pulmonary embolism (PE) may lead to cardiogenic shock or cardiac arrest with high mortality rates (65%) despite treatment with thrombolysis. Patients not responding to this therapy might benefit from extracorporeal life support (ECLS). Only occasional case reports of ECLS in PE patients are available. We studied the use of ECLS after thrombolysis in patients suffering from refractory cardiogenic shock due to PE. MATERIAL AND METHODS Patients who were admitted to our university intensive care unit (ICU) with PE, not responding to throm-bolysis, and who received subsequent ECLS treatment were studied. RESULTS 12 patients with severe PE were included. 6 patients were admitted by emergency medical services, 5 patients were transferred to the ICU from other hospitals and one patient presented at the emergency department by herself. 11 of 12 patients suffered from cardiac arrest and needed cardiopulmonary resuscitation (CPR) before ECLS implantation. Three ECLS were im-planted during CPR and nine ECLS were implanted during emergency conditions in patients with cardiogenic shock. All patients received thrombolysis before implementation of ECLS. Mean duration of ICU treatment was 22.4 ± 23.0 days. Mean duration of ECLS therapy was 5.6 ± 6.5 days. Bleeding complications occurred in four patients. Complications directly related to the ECLS system occurred in two patients (overall complication rate 42%). Overall, 6 of 12 patients (50%) survived. CONCLUSIONS ECLS may be considered as abailout therapy in PE patients not responding to prior definitive treatment such as thrombolysis. ECLS therapy seems to be feasible with an acceptable complication rate even after thrombolysis.
The ecological importance of crocodylians: towards evidence‐based justification for their conservation

Large‐bodied predators are well represented among the world's threatened and endangered species. A significant body of literature shows that in terrestrial and marine ecosystems large predators can play important roles in ecosystem structure and functioning. By contrast, the ecological roles and importance of large predators within freshwater ecosystems are poorly understood, constraining the design and implementation of optimal conservation strategies for freshwater ecosystems. Conservationists and environmentalists frequently promulgate ecological roles that crocodylians are assumed to fulfil, but often with limited evidence supporting those claims.
Effect of Self-Efficacy Enhancing Intervention Training on Clinical Health Status of Diabetic Patients at High-Risk for Leg Problems

Egypt has more diabetic individuals than any other country, with high incidence of foot problems and amputations. This study was aimed at evaluating the effect of a self-efficacy enhancing intervention training (SEEIP) on the clinical health status of diabetic patients at high risk for leg problems. The study was conducted in the diabetic outpatient clinic in Ain-Shams Specialized University Hospital in using a randomized controlled trial study design. It included a sample of 60 diabetic patients randomized an intervention group of 30 patients to attend the program and an equal control group following the routine diabetic care in the setting. The data collection tools were an interview questionnaire sheet, and adiabetes clinical/lab form, the self-efficacy assessment form for diabetic patients, and a leg physical assessment sheet. The study was carried out through preparatory, assessment, planning, implementation, and evaluation phases. The training intervention consisted of five efficacy-enhancing sessions at weekly intervals. For evaluation, two posttests were carried out at one and six months after the end of the program. The work was from September 2014 to August 2015. The study revealed statistically significant improvements in the study group at the post- and follow-up in lower limb physical findings (p<0.001), compliance with medications, more days of intake of medications, of following diet, exercise, and practicing foot care during last week (p<0.001), perception of health, and self-confidence (p<0.001), hypertension (p<0.001), random blood sugar (p<0.001), glycated Hb (p<0.001), and total cholesterol (p=0.001). There were statistically significant positive correlation between the scores of self-confidence and foot self-care (r=0.96), and between the number of abnormal signs and the level of HbA1c, while the total number of abnormal signs correlated negatively with the score of self-confidence and foot self-care. The level of HbA1c, it correlated negatively with the scores of self-confidence and foot self-care. In conclusion, increasing diabetic patients’ self-confidence and self-efficacy can improve their self-care practices, with subsequent positive impacts on their general and feet health status and diabetic control. The implementation of self-efficacy enhancing training programs is recommended with the use of the developed illustrated booklet as an educational aid for diabetic patients whom at risk for leg problems. More research is needed to investigate the longterm effect of such educational interventions.
Altered Cofactor Preference of Thermostable StDAPDH by a Single Mutation at K159

D-amino acid production from 2-keto acid by reductive amination is an attractive pathway because of its high yield and environmental safety. StDAPDH, a meso-diaminopimelate dehydrogenase (meso-DAPDH) from Symbiobacterium thermophilum, was the first meso-DAPDH to show amination of 2-keto acids. Furthermore, StDAPDH shows excellent thermostability compared to other meso-DAPDHs. However, the cofactor of StDAPDH is NADP(H), which is less common than NAD(H) in industrial applications. Therefore, cofactor engineering for StDAPDH is needed. In this study, the highly conserved cofactor binding sites around the adenosine moiety of NADPH were targeted to determine cofactor specificity. Lysine residues within a loop were found to be critical for the cofactor specificity of StDAPDH. Replacement of lysine with arginine resulted in the activity of pyruvic acid with NADH as the cofactor. The affinity of K159R to pyruvic acid was equal with NADH or NADPH as the cofactor, regardless of the mutation. Molecular dynamics simulations revealed that the large steric hindrance of arginine and the interaction of the salt bridge between NADH and arginine may have restricted the free movement of NADH, which prompted the formation of a stable active conformation of mutant K159R. These results provide further understanding of the catalytic mechanism of StDAPDH and guidance for the cofactor engineering of StDAPDH.
Recovery and drug dependency: a new deal for families.

The true meaning of recovery and the effect of drug use on the family are two topics of debate in the drug sector, but so far have not been sufficiently addressed as intertwining issues. With families increasingly recognised on the UK government agenda and a broad, holistic understanding of recovery becoming more accepted, it is wise to examine the links between family involvement and â? ~trueâ? T recovery. Drawing on a seminar held by Adfam and DrugScope on the positive role families can play in supporting recovery from drug dependency, this paper considers recovery and the family as mutually reinforcing and suggests ways of moving forward to improve outcomes for problematic drug users, their families and wider society.