Miracle-dz/UniFAR-FTUs huggingface dataset:
Spirituality in Daily Healthcare Provided in Brazil: Meanings and Practices of the Nursing Team

Objective: to understand the meanings and practices related to spirituality experienced by Nursing teams in the daily care provided in Oncology. Methods: qualitative research, guided by the theory of Holistic Nursing by Myra Levine, conducted with members of the Nursing team at an Oncology hospital in Brazil. Data collection was carried out in 2018, through an interview guided by a semi-structured script. Data analysis was performed using Lawrence Bardin's Content Analysis technique. Results: two categories emerged: the first brought to light the meanings attributed to spirituality by the Nursing team and the second category presented the practices of spiritual care by Nursing personnel in their daily routine in Oncology, highlighting that professionals address spirituality with patients in different ways. Conclusion: the approach to spirituality in Oncology care and in the professional training of Nursing personnel is essential, as a way of providing holistic and humanized care, thus strengthening the psycho-spiritual dimension in daily care.
Human Cytomegalovirus UL48 Deubiquitinase Primarily Targets Innermost Tegument Proteins pp150 and Itself To Regulate Their Stability and Protects Virions from Inclusion of Ubiquitin Conjugates

Herpesviruses encode highly conserved tegument proteins that contain deubiquitinase (DUB) activity. Although the role of viral DUBs in the regulation of host innate immune responses has been established, their roles in the stability and function of viral proteins are not well understood. ABSTRACT Viral deubiquitinases (DUBs) regulate cellular innate immunity to benefit viral replication. In human cytomegalovirus (HCMV), the UL48-encoded DUB regulates innate immune responses, including NF-κB signaling. Although UL48 DUB is known to regulate its stability via auto-deubiquitination, its impact on other viral proteins is not well understood. In this study, we investigated the role of UL48 DUB in regulating the ubiquitination of viral proteins by comparing the levels of ubiquitinated viral peptides in cells infected with wild-type virus and DUB active-site mutants using mass spectrometry. We found that ubiquitinated peptides were increased in DUB mutant virus infection for 90% of viral proteins, with the innermost tegument proteins pp150 (encoded by UL32) and pUL48 itself being most significantly affected. The highly deubiquitinated lysine residues of pUL48 were mapped within its N-terminal DUB domain and the nuclear localization signal. Among them, the arginine substitution of lysine 2 (K2R) increased pUL48 stability and enhanced viral growth at low multiplicity of infection, indicating that K2 auto-deubiquitination has a role in regulating pUL48 stability. pUL48 also interacted with pp150 and increased pp150 expression by downregulating its ubiquitination. Furthermore, we found that, unlike the wild-type virus, mutant viruses expressing the UL48 protein with the DUB domain deleted or DUB active site mutated contain higher levels of ubiquitin conjugates, including the ubiquitinated forms of pp150, in their virions. Collectively, our results demonstrate that UL48 DUB mainly acts on the innermost tegument proteins pp150 and pUL48 itself during HCMV infection and may play a role in protecting virions from the inclusion of ubiquitin conjugates. IMPORTANCE Herpesviruses encode highly conserved tegument proteins that contain deubiquitinase (DUB) activity. Although the role of viral DUBs in the regulation of host innate immune responses has been established, their roles in the stability and function of viral proteins are not well understood. In this study, we performed a comparative analysis of the levels of ubiquitinated viral peptides between wild-type and DUB-inactive HCMV infections and demonstrated that the innermost tegument proteins pp150 and pUL48 (DUB itself) are major targets of viral DUB. We also show that ubiquitinated viral proteins are effectively incorporated into the virions of DUB mutant viruses but not the wild-type virus. Our study demonstrates that viral DUBs may play important roles in promoting the stability of viral proteins and inhibiting the inclusion of ubiquitin conjugates into virions.
The ESC Guidelines on heart failure, sacubitril-valsartan in resistant hypertension, and new therapeutic targets in myocardial hypertrophy.

(i) a of the failure with mid-range ejection fraction’ to ‘heart failure with mildly reduced ejection fraction (HFmrrEF)’; (ii) a simplified diagnostic algorithm for heart with reduced ejection fraction (HFrEF); (iii) a treatment algorithm for HFrEF according to phenotypes; (iv) a modified classification for acute HF; (v) updated treatments for most non-cardiovascular comorbidities including hyperkalaemia, iron deficiency, and (vi) the role of genetic testing in cardiomyopathies and new treatments; and (vii) the addition of quality indicators.
Fragment evolution for GPCRs: the role of secondary binding sites in optimization.

We developed a docking-based fragment evolution approach that extends orthosteric fragments towards a less conserved secondary binding pocket of GPCRs. Evaluating 13 000 extensions for the β1- and β2-adrenergic receptors we synthesized and tested 112 bitopic molecules. Our results confirmed the positive contribution of the secondary binding pocket to both potency and selectivity optimizations.
Associations between migration experience and perceived mental health in optimal ageing: Evidence from the Sardinian Blue Zone

The effect of migration on perceived mental health has not been examined in older migrants after their return to their places of origin. This study was mainly aimed at evaluating the perceived mental health of older people who experienced migration and permanent resident peers living in the Sardinian Blue Zone (i.e. one of the four areas of exceptional longevity in the world). Forty‐eight community‐based older participants (32 males and 16 females) with and without a migration experience were recruited in two villages of the Sardinian Blue Zone and completed a battery of self‐report inventories assessing psychological well‐being, negative mood, and ego resilience. Older individuals who experienced migration reported higher ego resilience and exhibited greater resources used to manage positive emotionality (i.e. openness to life experiences). Moreover, compared to the normative data, both the groups reported higher psychological well‐being and fewer depressive symptoms. Finally, no significant associations were found between the length of migration and each mental health index. In conclusion, resilience seems to represent a psychological trait that helps to manage stressful events and contributes to the preservation of perceived mental health in late adulthood.
A Comparison of Protein Extraction Methods from Protease Treated Rubber Particles Suitable for 2-Dimensional Electrophoresis Study of Allergic Proteins

2017) Abstract Some proteins in latex products may cause allergic reactions to human. This research was to investigate protein profiling in Hevea brasiliensis clone RRIM 600 rubber particles. Protease from Bacillus subtilis MR10 and non-protease treated rubber particles were prepared from seven-year old rubber trees to evaluate proteomics by using two-dimensional electrophoresis (2-DE) analysis in IPG pH 3 – 10, 7 cm and 12.50% gel conditions with silver staining. There were three protein extraction methods, first method (50 mM HEPES-Tris pH 7.60), second method (0.50 % SDS) and third method (0.10 % SDS and 50 mM Tris-HCl pH 6.80). Results showed that three extraction methods in non-protease treated rubber were estimated to 20 spots (22-175 kDa, pI 3-9), 40 spots (22-175 kDa, pI 4-10) and 200 spots (14-95 kDa, pI 3-9), respectively and protease treated rubber were estimated to 10 spots (42-175 kDa, pI 4-7), 30 spots (22-175 kDa, pI 4-7) and 160 spots (14-95 kDa, pI 3-10), respectively. Thus, protease treatment could decrease some proteins in rubber particle and third method was suitable protein extraction procedure because of highest protein expression. Protein identification in some spots on Coomassie brilliant blue R-250 staining of this extraction method with liquid chromatography-tandem mass spectrometry (LC-MS MS –1 ) was also found four allergenic proteins (allergen Hev b 7, putative latex allergen Hev b 7.02, Hev 2.20 and small rubber particle protein Hev 3, respectively) on latex
Pancreatic Cancer: A Review.

Importance Pancreatic ductal adenocarcinoma (PDAC) is a relatively uncommon cancer, with approximately 60 430 new diagnoses expected in 2021 in the US. The incidence of PDAC is increasing by 0.5% to 1.0% per year, and it is projected to become the second-leading cause of cancer-related mortality by 2030. Observations Effective screening is not available for PDAC, and most patients present with locally advanced (30%-35%) or metastatic (50%-55%) disease at diagnosis. A multidisciplinary management approach is recommended. Localized pancreas cancer includes resectable, borderline resectable (localized and involving major vascular structures), and locally advanced (unresectable) disease based on the degree of arterial and venous involvement by tumor, typically of the superior mesenteric vessels. For patients with resectable disease at presentation (10%-15%), surgery followed by adjuvant chemotherapy with FOLFIRINOX (fluorouracil, irinotecan, leucovorin, oxaliplatin) represents a standard therapeutic approach with an anticipated median overall survival of 54.4 months, compared with 35 months for single-agent gemcitabine (stratified hazard ratio for death, 0.64 [95% CI, 0.48-0.86]; P = .003). Neoadjuvant systemic therapy with or without radiation followed by evaluation for surgery is an accepted treatment approach for resectable and borderline resectable disease. For patients with locally advanced and unresectable disease due to extensive vascular involvement, systemic therapy followed by radiation is an option for definitive locoregional disease control. For patients with advanced (locally advanced and metastatic) PDAC, multiagent chemotherapy regimens, including FOLFIRINOX, gemcitabine/nab-paclitaxel, and nanoliposomal irinotecan/fluorouracil, all have a survival benefit of 2 to 6 months compared with a single-agent gemcitabine. For the 5% to 7% of patients with a BRCA pathogenic germline variant and metastatic PDAC, olaparib, a poly (adenosine diphosphate [ADB]-ribose) polymerase inhibitor, is a maintenance option that improves progression-free survival following initial platinum-based therapy. Conclusions and Relevance Approximately 60 000 new cases of PDAC are diagnosed per year, and approximately 50% of patients have advanced disease at diagnosis. The incidence of PDAC is increasing. Currently available cytotoxic therapies for advanced disease are modestly effective. For all patients, multidisciplinary management, comprehensive germline testing, and integrated supportive care are recommended.
Zebrafish research in Greece: swimming against the current.

Zebrafish is a vertebrate model extensively used in Developmental Biology and Human Disease modeling as it shares high genetic and physiological similarities with humans. It has become the second most popular animal model, following mice, with several advantages: zebrafish are easily housed and cared for, the cost of installing and maintaining a zebrafish facility is significantly lower than mice, they reproduce often and develop quickly. Using zebrafish complies with the 3Rs principles of laboratory animal use. Zebrafish embryos develop externally and are transparent, allowing for in vivo non-invasive imaging. There are many transgenic and mutant lines available that mimic most Human Diseases, including reporter lines for most signaling pathways. There are also several reverse genetic tools to functionally verify genes or variants of unknown significance, identified in Genome-Wide Association Studies (GWAS) or using Next Generation Sequencing (NGS) approaches. In addition, the model emerges as an invaluable whole animal platform for various stages of drug discovery efforts by exploring the ability to do high-throughput phenotypic-driven screens. These include phenotypic screenings, determinations of general and/or specific toxicity (cardiac, renal, hepatotoxicity etc.), and mechanism of action studies. Finally, zebrafish are able to retain their capacity to regenerate most organs during their entire life span, making them a well-established model to study organ regeneration. The European Zebrafish Society consists of more than 180 research labs throughout Europe. In Greece however, zebrafish use remains rather limited. I present here a brief historical overview of zebrafish research in Greece.
Hyperexcitable interneurons trigger cortical spreading depression in an Scn1a migraine model

Cortical spreading depression (CSD), a wave of depolarization followed by depression of cortical activity, is a pathophysiological process implicated in migraine with aura and various other brain pathologies, such as ischemic stroke and traumatic brain injury. To gain insight into the pathophysiology of CSD, we generated a mouse model for a severe monogenic subtype of migraine with aura, familial hemiplegic migraine type 3 (FHM3). FHM3 is caused by mutations in SCN1A, encoding the voltage-gated Na+ channel NaV1.1 predominantly expressed in inhibitory interneurons. Homozygous Scn1aL1649Q knock-in mice died prematurely, whereas heterozygous mice had a normal lifespan. Heterozygous Scn1aL1649Q knock-in mice compared with WT mice displayed a significantly enhanced susceptibility to CSD. We found L1649Q to cause a gain-of-function effect with an impaired Na+-channel inactivation and increased ramp Na+ currents leading to hyperactivity of fast-spiking inhibitory interneurons. Brain slice recordings using K+-sensitive electrodes revealed an increase in extracellular K+ in the early phase of CSD in heterozygous mice, likely representing the mechanistic link between interneuron hyperactivity and CSD initiation. The neuronal phenotype and premature death of homozygous Scn1aL1649Q knock-in mice was partially rescued by GS967, a blocker of persistent Na+ currents. Collectively, our findings identify interneuron hyperactivity as a mechanism to trigger CSD.
Remineralization effects of self‐assembling peptide P11‐4 associated with three materials on early enamel carious lesions: An in vitro study

The aim of this study was to assess the remineralization of enamel caries lesions using the self‐assembling peptide P11‐4 associated with different materials. Artificial early enamel lesions were prepared on 154 primary teeth. The samples were randomly divided into eight groups: (1) control, (2) P11‐4, (3) fluoridate toothpaste (FT), (4) P11‐4 + FT, (5) casein phosphopeptide–amorphous calcium phosphate (CPP–ACP), (6) P11‐4 + CPP–ACP, (7) fluoridate bioactive glass toothpaste (BT), and (8) P11‐4 + BT. The surface enamel microhardness (EMH) and energy‐dispersive X‐ray spectroscopy (EDS) of the teeth were then measured at the baseline, after demineralization, and after 28 days of remineralization. The enamel surfaces were assessed by field emission scanning electron microscopy (FESEM) and atomic force microscopy (AFM). The data were analyzed with one‐way analysis of variance (ANOVA) (p < .05). EMH after demineralization was significantly lower than the baseline value (p < .001). The interventions led to an enhanced percentage of EMH recovery (%REMH), which was higher in Groups 6 and 7. There was no significant difference between Groups 3 and 4. Groups 1 and 2 had the lowest %REMH. The mean calcium/phosphate weight percentage ratio of P11‐4 was significantly lower than the others (p < .001). The FESEM and AFM images revealed mineral deposition on the eroded enamel and reductions in surface roughness in Groups 5 and 7.
Associations of death‐preparedness states with bereavement outcomes for family caregivers of terminally ill cancer patients

Death preparedness involves cognitive prognostic awareness and emotional acceptance of a relative's death. Effects of retrospectively assessed cognitive prognostic awareness and emotional preparedness for patient death have been individually investigated among bereaved family caregivers. We aimed to prospectively examine associations of caregivers' death‐preparedness states, determined by conjoint cognitive prognostic awareness and emotional preparedness for death, with bereavement outcomes.
Achieving remission or low disease activity is associated with better outcomes in patients with systemic lupus erythematosus: a systematic literature review

Background Remission and low disease activity (LDA) have been proposed as the treatment goals for patients with systemic lupus erythematosus (SLE). Several definitions for each have been proposed in the literature. Objective To assess the impact of remission/LDA according to various definitions on relevant outcomes in patients with SLE. Methods This systematic literature review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses using PubMed (1946–week 2, April 2021), Cochrane library (1985–week 2, week 2, April 2021) and EMBASE (1974–week 2, April 2021). We included longitudinal and cross-sectional studies in patients with SLE reporting the impact of remission and LDA (regardless their definition) on mortality, damage accrual, flares, health-related quality of life and other outcomes (cardiovascular risk, hospitalisation and direct costs). The quality of evidence was evaluated using the Newcastle-Ottawa Scale. Results We identified 7497 articles; of them, 31 studies met the inclusion criteria and were evaluated. Some articles reported a positive association with survival, although this was not confirmed in all of them. Organ damage accrual was the most frequently reported outcome, and remission and LDA were reported as protective of this outcome (risk measures varying from 0.04 to 0.95 depending on the definition). Similarly, both states were associated with a lower probability of SLE flares, hospitalisations and a better health-related quality of life, in particular the physical domain. Conclusion Remission and LDA are associated with improvement in multiple outcomes in patients with SLE, thus reinforcing their relevance in clinical practice. PROSPERO registration number CRD42020162724.
Structural basis for antibody binding to adenylate cyclase toxin reveals RTX linkers as neutralization-sensitive epitopes

RTX leukotoxins are a diverse family of prokaryotic virulence factors that are secreted by the type 1 secretion system (T1SS) and target leukocytes to subvert host defenses. T1SS substrates all contain a C-terminal RTX domain that mediates recruitment to the T1SS and drives secretion via a Brownian ratchet mechanism. Neutralizing antibodies against the Bordetella pertussis adenylate cyclase toxin, an RTX leukotoxin essential for B. pertussis colonization, have been shown to target the RTX domain and prevent binding to the αMβ2 integrin receptor. Knowledge of the mechanisms by which antibodies bind and neutralize RTX leukotoxins is required to inform structure-based design of bacterial vaccines, however, no structural data are available for antibody binding to any T1SS substrate. Here, we determine the crystal structure of an engineered RTX domain fragment containing the αMβ2-binding site bound to two neutralizing antibodies. Notably, the receptor-blocking antibodies bind to the linker regions of RTX blocks I–III, suggesting they are key neutralization-sensitive sites within the RTX domain and are likely involved in binding the αMβ2 receptor. As the engineered RTX fragment contained these key epitopes, we assessed its immunogenicity in mice and showed that it elicits similar neutralizing antibody titers to the full RTX domain. The results from these studies will support the development of bacterial vaccines targeting RTX leukotoxins, as well as next-generation B. pertussis vaccines.
Promoting Safe Sleep, Tobacco Cessation, and Breastfeeding to Rural Women During the COVID-19 Pandemic: Quasi-Experimental Study

Background Safe Sleep Community Baby Showers address strategies to prevent sleep-related infant deaths. Due to the COVID-19 pandemic, these events transitioned from in-person to virtual. Objective This study describes outcomes of transitioning Safe Sleep Community Baby Showers to a virtual format and compares outcomes to previous in-person events. Methods Participants from four rural Kansas counties were emailed the presurvey, provided educational materials (videos, livestream, or digital documents), and completed a postsurvey. Those who completed both surveys received a portable crib and wearable blanket. Within-group comparisons were assessed between pre- and postsurveys; between-group comparisons (virtual vs in-person) were assessed by postsurveys. Results Based on data from 145 in-person and 74 virtual participants, virtual participants were more likely to be married (P<.001) and have private insurance (P<.001), and were less likely to report tobacco use (P<.001). Both event formats significantly increased knowledge and intentions regarding safe sleep and avoidance of secondhand smoke (all P≤.001). Breastfeeding intentions did not change. Differences were observed between in-person and virtual meetings regarding confidence in the ability to avoid secondhand smoke (in-person: 121/144, 84% vs virtual: 53/74, 72%; P=.03), intention to breastfeed ≥6 months (in-person: 79/128, 62% vs virtual: 52/66, 79%; P=.008), and confidence in the ability to breastfeed ≥6 months (in-person: 58/123, 47% vs virtual: 44/69, 64%; P=.02). Conclusions Although both event formats demonstrated increased knowledge/intentions to follow safe sleep recommendations, virtual events may further marginalize groups who are at high risk for poor birth outcomes. Strategies to increase technology access, recruit priority populations, and ensure disparities are not exacerbated will be critical for the implementation of future virtual events.
Wax inhibitor based on ethylene vinyl acetate with methyl methacrylate and diethanolamine for crude oil pipeline

Wax precipitation and deposition is one of the most significant flow assurance challenges in the production system of the crude oil. Wax inhibitors are developed as a preventive strategy to avoid an absolute wax deposition. Wax inhibitors are polymers which can be known as pour point depressants as they impede the wax crystals formation, growth, and deposition. In this study three formulations of wax inhibitors were prepared, ethylene vinyl acetate, ethylene vinyl acetate co-methyl methacrylate (EVA co-MMA) and ethylene vinyl acetate co-diethanolamine (EVA co-DEA) and the comparison of their efficiencies in terms of cloud point¸ pour point, performance inhibition efficiency (%PIE) and viscosity were evaluated. The cloud point and pour point for both EVA and EVA co-MMA were similar, 15°C and 10-5°C, respectively. Whereas, the cloud point and pour point for EVA co-DEA were better, 10°C and 10-5°C respectively. In conclusion, EVA co-DEA had shown the best % PIE (28.42%) which indicates highest percentage reduction of wax deposit as compared to the other two inhibitors.