Miracle-dz/UniFAR-FTUs huggingface dataset:
Instruments for quality of life assessment in individuals with human papillomavirus.

OBJECTIVE To identify scientific evidence on quality of life measurement instruments used in individuals with infections caused by human papillomavirus. METHOD This was an integrative review carried out from April 1995 to March 2017 in the LILACS, SciVerse Scopus, ISI Web of Science, CINAHL, and PubMed databases. The controlled descriptors adopted were: Infecções por Papilomavirus; Qualidade de Vida; Papillomavirus Infections; and Quality of Life. RESULTS Of the 416 articles found, 12 were selected. Thirteen different types of instruments to evaluate the quality of life of individuals with human papillomavirus were identified, in that nine were generic and four specific. CONCLUSION Different generic and specific instruments were used to evaluate the quality of life of individuals with human papillomavirus, which means no consensus or preference among the studies was identified. However, a lack of use of specific instruments to evaluate this construct in this population was observed.
Genetic Ablation of Neural Progenitor Cells Impairs Acquisition of Trace Eyeblink Conditioning

Abstract Adult-born neurons are believed to play a role in memory formation by providing enhanced plasticity to the hippocampus. Past studies have demonstrated that reduction of neurogenesis impairs associative learning, but these experiments used irradiation or neurotoxic substances, which may have had unintended off-target effects. Therefore, to investigate the role of these adult-born neurons more precisely, we used nestin-HSV-TK transgenic mice (Nes-TK) to selectively ablate newborn neurons. Nes-TK mice were fed a chow infused with valganciclovir to induce the ablation of neural progenitor cells. After being on this diet for 4 weeks, mice were trained on trace eyeblink conditioning, a hippocampus-dependent temporal associative memory task. Following the completion of training, brain sections from these animals were stained for doublecortin, a marker for immature neurons, to quantify levels of neurogenesis. We found that male transgenic mice on valganciclovir had significantly decreased amounts of doublecortin relative to male control animals, indicating a successful reduction in levels of neurogenesis. In conjunction with this reduction in neurogenesis, the male transgenic mice on valganciclovir learned at a significantly slower rate than male control mice. The female Nes-TK mice on valganciclovir showed no significant decrease in neurogenesis and no behavioral impairment relative to female control mice. Ultimately, the results are consistent with, and expand upon, prior studies that demonstrated that adult-born neurons are involved in the formation of associative memories. This study also provides a foundation to continue to explore the physiological role of newborn neurons with in vivo recordings during behavioral training.
Re-thinking recovery in post-conflict settings: Supporting the mental well-being of communities in Colombia

ABSTRACT Addressing mental health needs is a central focus of the Colombian Government’s framework for socio-political reconstruction following over 60 years of conflict. Informed by WHO standards, country efforts utilise biopsychosocial models that prioritise individual psychological and psychiatric conditions. However, increasing scrutiny of the deployment of Western approaches to mental health and recovery in the global south suggests a need to explore the best route to improving mental health outcomes. Our research contributes to these debates through a qualitative study of local understandings of mental health recovery related concepts among internally displaced persons in Colombia. Analysis of focus groups with 40 internally displaced men and women established definitions for emotional distress and recovery as parallel processes linked to the fracture and rebuilding of social worlds and family life. Definitions were shaped heavily by cultural, political, economic and legal contexts of everyday survival, often linked to experiences of structural and symbolic forms of violence. We conclude that a locally informed mental health recovery model that stretches beyond individual experiences of mental ill-health to promote ideas of collective social change would be best suited to addressing mental health needs of internally displaced groups in Colombia. Implications for practice are discussed.
Guadecitabine Plus Ipilimumab in Unresectable Melanoma: The NIBIT-M4 Clinical Trial

Purpose: The immunomodulatory activity of DNA hypomethylating agents (DHAs) suggests they may improve the effectiveness of cancer immunotherapies. The phase Ib NIBIT-M4 trial tested this hypothesis using the next-generation DHA guadecitabine combined with ipilimumab. Patients and Methods: Patients with unresectable stage III/IV melanoma received escalating doses of guadecitabine 30, 45, or 60 mg/m2/day subcutaneously on days 1 to 5 every 3 weeks, and ipilimumab 3 mg/kg intravenously on day 1 every 3 weeks, starting 1 week after guadecitabine, for four cycles. Primary endpoints were safety, tolerability, and MTD of treatment; secondary were immune-related (ir) disease control rate (DCR) and objective response rate (ORR); and exploratory were changes in methylome, transcriptome, and immune contextures in sequential tumor biopsies, and pharmacokinetics. Results: Nineteen patients were treated; 84% had grade 3/4 adverse events, and neither dose-limiting toxicities per protocol nor overlapping toxicities were observed. Ir-DCR and ir-ORR were 42% and 26%, respectively. Median CpG site methylation of tumor samples (n = 8) at week 4 (74.5%) and week 12 (75.5%) was significantly (P < 0.05) lower than at baseline (80.3%), with a median of 2,454 (week 4) and 4,131 (week 12) differentially expressed genes. Among the 136 pathways significantly (P < 0.05; Z score >2 or ←2) modulated by treatment, the most frequently activated were immune-related. Tumor immune contexture analysis (n = 11) demonstrated upregulation of HLA class I on melanoma cells, an increase in CD8+, PD-1+ T cells and in CD20+ B cells in posttreatment tumor cores. Conclusions: Treatment of guadecitabine combined with ipilimumab is safe and tolerable in advanced melanoma and has promising immunomodulatory and antitumor activity.
Discordance between eNOS phosphorylation and activation revealed by multispectral imaging and chemogenetic methods

Significance Nitric oxide (NO) is synthesized by the endothelial isoform of nitric oxide synthase (eNOS) in vascular endothelial cells. The high reactivity of NO undermines its accurate detection in living cells. The direct detection of the low physiological concentrations of NO that are present in endothelial cells represents a significant analytical challenge. In these studies, we have used powerful biosensors to measure NO and other key signaling molecules in living endothelial cells in real time using fluorescence microscopy. These approaches have provided insights into the mechanisms whereby NO synthesis is regulated and call into question many prior conclusions about the intracellular pathways that regulate eNOS. Nitric oxide (NO) synthesized by the endothelial isoform of nitric oxide synthase (eNOS) is a critical determinant of vascular homeostasis. However, the real-time detection of intracellular NO—a free radical gas—has been difficult, and surrogate markers for eNOS activation are widely utilized. eNOS phosphorylation can be easily measured in cells by probing immunoblots with phosphospecific antibodies. Here, we pursued multispectral imaging approaches using biosensors to visualize intracellular NO and Ca2+ and exploited chemogenetic approaches to define the relationships between NO synthesis and eNOS phosphorylation in cultured endothelial cells. We found that the G protein-coupled receptor agonists adenosine triphosphate (ATP) and histamine promoted rapid increases in eNOS phosphorylation, as did the receptor tyrosine kinase agonists insulin and Vascular Endothelial Growth Factor (VEGF). Histamine and ATP also promoted robust NO formation and increased intracellular Ca2+. By contrast, neither insulin nor VEGF caused any increase whatsoever in intracellular NO or Ca2+—despite eliciting strong eNOS phosphorylation responses. Our findings demonstrate an unexpected and striking discordance between receptor-modulated eNOS phosphorylation and NO formation in endothelial cells. Previous reports in which phosphorylation of eNOS has been studied as a surrogate for enzyme activation may need to be reassessed.
Mitochondria orchestrate proteostatic and metabolic stress responses

The eukaryotic cell is morphologically and functionally organized as an interconnected network of organelles that responds to stress and aging. Organelles communicate via dedicated signal transduction pathways and the transfer of information in form of metabolites and energy levels. Recent data suggest that the communication between organellar proteostasis systems is a cornerstone of cellular stress responses in eukaryotic cells. Here, we discuss the integration of proteostasis and energy fluxes in the regulation of cellular stress and aging. We emphasize the molecular architecture of the regulatory transcriptional pathways that both sense and control metabolism and proteostasis. A special focus is placed on mechanistic insights gained from the model organism budding yeast in signaling from mitochondria to the nucleus and how this shapes cellular fitness.
A Na+ leak channel cloned from Trichoplax adhaerens extends extracellular pH and Ca2+ sensing for the DEG/ENaC family close to the base of Metazoa

Acid-sensitive ion channels belonging to the degenerin/epithelial sodium channel (DEG/ENaC) family activate in response to extracellular protons and are considered unique to deuterostomes. However, sensitivity to pH/protons is more widespread, where, for example, human ENaC Na+ leak channels are potentiated and mouse BASIC and Caenorhabditis elegans ACD-1 Na+ leak channels are blocked by extracellular protons. For many DEG/ENaC channels, extracellular Ca2+ ions modulate gating, and in some cases, the binding of protons and Ca2+ is interdependent. Here, we functionally characterize a DEG/ENaC channel from the early-diverging animal Trichoplax adhaerens, TadNaC6, that conducts Na+-selective leak currents in vitro sensitive to blockade by both extracellular protons and Ca2+. We determine that proton block is enhanced in low external Ca2+ concentration, whereas calcium block is enhanced in low external proton concentration, indicative of competitive binding of these two ligands to extracellular sites of the channel protein. TadNaC6 lacks most determinant residues for proton and Ca2+ sensitivity in other DEG/ENaC channels, and a mutation of one conserved residue (S353A) associated with Ca2+ block in rodent BASIC channels instead affected proton sensitivity, all indicative of independent evolution of H+ and Ca2+ sensitivity. Strikingly, TadNaC6 was potently activated by the general DEG/ENaC channel blocker amiloride, a rare feature only reported for the acid-activated channel ASIC3. The sequence and structural divergence of TadNaC6, coupled with its noncanonical functional features, provide unique opportunities for probing the proton, Ca2+, and amiloride regulation of DEG/ENaC channels and insight into the possible core-gating features of ancestral ion channels.
Chromosomal microarray analysis in prenatal diagnosis: ethical considerations of the Belgian approach

Detection of genetic aberrations in prenatal samples, obtained through amniocentesis or chorion villus biopsy, is increasingly performed using chromosomal microarray (CMA), a technique that can uncover both aneuploidies and copy number variants throughout the genome. Despite the obvious benefits of CMA, the decision on implementing the technology is complicated by ethical issues concerning variant interpretation and reporting. In Belgium, uniform guidelines were composed and a shared database for prenatal CMA findings was established. This Belgian approach sparks discussion: it is evidence-based, prevents inconsistencies and avoids parental anxiety, but can be considered paternalistic. Here, we reflect on the cultural and moral bases of the Belgian reporting system of prenatally detected variants.
Different Methods of Dispersing Carbon Nanotubes in Epoxy Resin and Initial Evaluation of the Obtained Nanocomposite as a Matrix of Carbon Fiber Reinforced Laminate in Terms of Vibroacoustic Performance and Flammability

Different industrial mixing methods and some of their combinations ((1) ultrasound; (2) mechanical stirring; (3) by roller machine; (4) by gears machine; and (5) ultrasound radiation + high stirring) were investigated for incorporating multi-walled carbon nanotubes (MWCNT) into a resin based on an aeronautical epoxy precursor cured with diaminodiphenylsulfone (DDS). The effect of different parameters, ultrasound intensity, number of cycles, type of blade, and gear speed on the nanofiller dispersion were analyzed. The inclusion of the nanofiller in the resin causes a drastic increase in the viscosity, preventing the homogenization of the resin and a drastic increase in temperature in the zones closest to the ultrasound probe. To face these challenges, the application of high-speed agitation simultaneously with the application of ultrasonic radiation was applied. This allowed, on the one hand, a homogeneous dispersion, and on the other hand, an improvement of the dissipation of heat generated by ultrasonic radiation. The most efficient method was a combination of ultrasound radiation assisted by a high stirring method with the calendar, which was used for the preparation of a carbon fiber reinforced panel (CFRP). The manufactured panel was subjected to dynamic and vibroacoustic tests in order to characterize structural damping and sound transmission loss properties. Under both points of view, the new formulation demonstrated an improved efficiency with reference to a standard CFRP equivalent panel. In fact, for this panel, the estimated damping value was well above the average of the typical values representative of the carbon fiber laminates (generally less than 1%), and also a good vibroacoustic performance was detected as the nanotube based panel exhibited a higher sound transmission loss (STL) at low frequencies, in correspondence with the normal mode participation region. The manufactured panel was also characterized in terms of fire performance using a cone calorimeter and the results were compared to those obtained using a commercially available monocomponent RTM6 (Hexcel composites) epoxy aeronautic resin with the same process and the same fabric and lamination. Compared to the traditional RTM6 resin, the panel with the epoxy nanofilled resin exhibits a significant improvement in fire resistance properties both in terms of a delay in the ignition time and in terms of an increase in the thermal resistance of the material. Compared to the traditional panel, made in the same conditions as the RTM6 resin, the time of ignition of the nanotube-based panel increased by 31 seconds while for the same panel, the heat release rate at peak, the average heat release rate, and the total heat release decreased by 21.4%, 48.5%, and 15%, respectively. The improvement of the fire performance was attributed to the formation of a non-intumescent char due to the simultaneous presence of GPOSS and carbon nanotubes.
Statistical Copolymers of n-Butyl Vinyl Ether and 2-Chloroethyl Vinyl Ether via Metallocene-Mediated Cationic Polymerization. A Scaffold for the Synthesis of Graft Copolymers

The cationic statistical copolymerization of n-butyl (be) and 2-chloroethyl vinyl ether (CEVE), is efficiently conducted using bis(η5-cyclopentadienyl)dimethyl zirconium (Cp2ZrMe2) in combination with tetrakis(pentafluorophenyl)borate dimethylanilinum salt [B(C6F5)4]–[Me2NHPh]+, as an initiation system. The reactivity ratios are calculated using both linear graphical and non-linear methods. Structural parameters of the copolymers are obtained by calculating the dyad sequence fractions and the mean sequence length, which are derived using the monomer reactivity ratios. The glass transition temperatures (Tg) of the copolymers are measured by Differential Scanning Calorimetry (DSC), and the results are compared with predictions based on several theoretical models. The statistical copolymers are further employed as scaffolds for the synthesis of graft copolymers having poly(vinyl ether)s as a backbone and either poly(ε-caprolactone) (PCL) or poly(l-lactide) (PLLA) as side chains. Both the grafting “onto” and the grafting “from” methodologies are employed. The reaction sequence is monitored by Size Exclusion Chromatography (SEC), NMR and IR spectroscopies. The advantages and limitations of each approach are thoroughly examined.
Development of Anncaliia algerae (Microsporidia) in Drosophila melanogaster

Representatives of the genus Anncaliia are known as natural parasites of dipteran and coleopteran insects, amphipod crustaceans, but also humans, primarily with immunodeficiency. Anncaliia algerae‐caused fatal myositis is considered as an emergent infectious disease in humans. A. (=Nosema, Brachiola) algerae, the best studied species of the genus, demonstrates the broadest among microsporidia range of natural and experimental hosts, but it has never been propagated in Drosophila. We present ultrastructural analysis of development of A. algerae in visceral muscles and adipocytes of Drosophila melanogaster 2 wk after per oral experimental infection. We observed typical to Anncaliia spp. features of ultrastructure and cell pathology including spore morphology, characteristic extensions of the plasma membrane, and presence of “ridges” and appendages of tubular material at proliferative stages. Anncaliia algerae development in D. melanogaster was particularly similar to one of A. algerae and A. (Brachiola) vesicularum in humans with acute myositis. Given D. melanogaster is currently the most established genetic model, with a fully sequenced genome and easily available transgenic forms and genomic markers, a novel host–parasite system might provide new genetic tools to investigate host–pathogen interactions of A. algerae, as well to test antimicrosporidia drugs.
Treatment of persistent post-traumatic headache and post-concussion symptoms using rTMS: a pilot, double-blind, randomized controlled trial.

Persistent post-traumatic headache (PTH) following mild traumatic brain injury (mTBI) is one of the most prominent and highly reported persistent post-concussion symptoms (PPCS). Non-pharmacologic treatments, including non-invasive neurostimulation technologies, have been proposed for use. Our objective was to evaluate headache characteristics at one-month following repetitive transcranial magnetic stimulation (rTMS) treatment in participants with PTH and PPCS. A double-blind, randomized, sham-controlled, pilot clinical trial was performed on twenty participants (18-65 years) with persistent PTH (ICHD-3) and PPCS (ICD-10). Ten sessions of rTMS therapy (10Hz, 600 pulses, 70% resting motor threshold amplitude) were delivered to the left dorsolateral prefrontal cortex (DLPFC). The primary outcome was a change in headache frequency or severity at one-month post-rTMS. Two-week long daily headache diaries and clinical questionnaires assessing function, PPCS, cognition, quality of life, and mood were completed at baseline, post-treatment, and at one-, three-, and six-months post-rTMS. A two-way (treatment x time) mixed ANOVA indicated a significant overall time effect for average headache severity [F(3,54)= 3.214, p=0.03] and a reduction in headache frequency at one-month post-treatment (#/two-weeks: REAL -5.2 (SD=5.8), SHAM -3.3 (SD=7.7). Secondary outcomes revealed an overall time interaction for headache impact, depression, post-concussion symptoms, and quality of life. There was a significant reduction in depression rating in the REAL group between baseline and one-month post-treatment, with no change in the SHAM group (PHQ-9; REAL -4.3 (SD=3.7, p=0.020), SHAM -0.7 (SD=4.7, p=1.0), Bonferroni corrected). In the REAL group, 60% returned to work while only 10% returned in the SHAM group (p=0.027). This pilot study demonstrates an overall time effect on headache severity, functional impact, depression, PPCS, and quality of life following rTMS treatment in participants with persistent PTH, however, findings were below clinical significance thresholds. There was a 100% response rate, no dropouts, and minimal adverse effects, warranting a larger phase II study.
Prevalence, Antibiogram, and Resistance Profile of Extended-Spectrum β-Lactamase-Producing Escherichia coli Isolates from Pig Farms in Luzon, Philippines.

This cross-sectional study was conducted to determine the prevalence, antibiogram, and resistance profile of extended-spectrum β-lactamase-producing Escherichia coli (ESBL-EC) isolates from healthy pigs and pig farms in Luzon, Philippines. A total of 162 rectal samples from healthy finisher and breeder pigs and boot swab samples from pig houses were collected from 54 randomly selected pig farms. Bacteria were isolated and screened using MacConkey agar plate supplemented with 1 mg/L cefotaxime. Identification of bacteria and antimicrobial susceptibility test were carried out through Vitek® 2 and combined disk test. PCR amplifications were carried out in all isolates targeting blaCTX-M and its five major groupings, blaTEM, and blaSHV. The farm prevalence of ESBL-EC was 57.41% (95% confidence interval [CI] = 43.21-70.77). A total of 48 (29.63%) ESBL-EC isolates were isolated from samples that showed 14 different phenotypic multidrug resistance patterns. The prevalence of blaCTX-M gene was 91.67% (95% CI = 80.02-97.68). All major blaCTX-M-groups except blaCTX-M-25group were detected. The blaCTX-M-1 was the most prevalent blaCTX-M gene, 75.0% (95% CI = 60.40-86.36). The prevalence of blaTEM and blaSHV genes was 91.67% (95% CI = 80.02-97.68) and 60.42% (95% CI = 45.27-74.23), respectively. Coexistence of different blaCTX-M, blaTEM, and blaSHV genes was observed in 44 isolates with 20 different genotypic patterns. High prevalence, diverse antibiogram profile, and genotypic resistance pattern of ESBL-EC isolates from healthy pigs and pig farms were observed in this study that could result in possible transmission to farm workers, susceptible bacteria, and the environment.
How Children of Parents With Dementia Can Make Their Subject Positions Understandable and Meaningful

The families of people diagnosed with dementia are commonly first-in-line caregivers. This can have a considerable effect on their lives, health, and relationships. However, few studies have focused on the children in such families. Therefore, the aim of this study was to describe how children, in their own narratives, construct themselves as subjects growing up and caring for a parent with dementia. The study applies discourse analysis. The findings show three subject positions: parent to your parent(s), orphan with parents, and time traveler stuck in time. There is a need to support these children, both as children and as young adults. More knowledge is necessary regarding the kind of support they might want or need. For health care professionals, it is important to know that it might not always be easy to ask for information or support as a child caring for a sick parent.