Miracle-dz/UniFAR-FTUs huggingface dataset:
Next-Generation Pertussis Vaccines Based on the Induction of Protective T Cells in the Respiratory Tract

Immunization with current acellular pertussis (aP) vaccines protects against severe pertussis, but immunity wanes rapidly after vaccination and these vaccines do not prevent nasal colonization with Bordetella pertussis. Studies in mouse and baboon models have demonstrated that Th1 and Th17 responses are integral to protective immunity induced by previous infection with B. pertussis and immunization with whole cell pertussis (wP) vaccines. Mucosal Th17 cells, IL-17 and secretory IgA (sIgA) are particularly important in generating sustained sterilizing immunity in the nasal cavity. Current aP vaccines induce potent IgG and Th2-skewed T cell responses but are less effective at generating Th1 and Th17 responses and fail to prime respiratory tissue-resident memory T (TRM) cells, that maintain long-term immunity at mucosal sites. In contrast, a live attenuated pertussis vaccine, pertussis outer membrane vesicle (OMV) vaccines or aP vaccines formulated with novel adjuvants do induce cellular immune responses in the respiratory tract, especially when delivered by the intranasal route. An increased understanding of the mechanisms of sustained protective immunity, especially the role of respiratory TRM cells, will facilitate the development of next generation pertussis vaccines that not only protect against pertussis disease, but prevent nasal colonization and transmission of B. pertussis.
White matter tract microstructure and cognitive performance after transient ischemic attack

Background and purpose Patients with transient ischemic attack (TIA) show evidence of cognitive impairment but the reason is not clear. Measurement of microstructural changes in white matter (WM) using diffusion tensor imaging (DTI) may be a useful outcome measure. We report WM changes using DTI and the relationship with neuropsychological performance in a cohort of transient ischemic attack (TIA) and non-TIA subjects. Methods Ninety-five TIA subjects and 51 non-TIA subjects were assessed using DTI and neuropsychological batteries. Fractional anisotropy (FA) and mean diffusivity (MD) maps were generated and measurements were collected from WM tracts. Adjusted mixed effects regression modelled the relationship between groups and DTI metrics. Results Transient ischemic attack subjects had a mean age of 67.9 ± 9.4 years, and non-TIA subjects had a mean age 64.9 ± 9.9 years. The TIA group exhibited higher MD values in the fornix (0.36 units, P < 0.001) and lower FA in the superior longitudinal fasciculus (SLF) (-0.29 units, P = 0.001), genu (-0.22 units, P = 0.016), and uncinate fasciculus (UF) (-0.26 units, P = 0.004). Compared to non-TIA subjects, subjects with TIA scored lower on the Addenbrooke’s Cognitive Assessment-Revised (median score 95 vs 91, P = 0.01) but showed no differences in scores on the Montreal Cognitive Assessment (median 27 vs 26) or the Mini-Mental State Examination (median 30). TIA subjects had lower scores in memory (median 44 vs 52, P < 0.01) and processing speed (median 45 vs 62, P < 0.01) but not executive function, when compared to non-TIA subjects. Lower FA and higher MD in the fornix, SLF, and UF were associated with poorer performance on tests of visual memory and executive function but not verbal memory. Lower FA in the UF and fornix were related to higher timed scores on the TMT-B (P < 0.01), and higher SLF MD was related to higher scores on TMT-B (P < 0.01), confirming worse executive performance in the TIA group. Conclusions DTI scans may be useful for detecting microstructural disease in TIA subjects before cognitive symptoms develop. DTI parameters, white matter hyperintensities, and vascular risk factors underly some of the altered neuropsychological measures in TIA subjects.
Fourth ventricle tumors in children: complications and influence of surgical approach.

OBJECTIVES The goal of this study was to characterize the complications and morbidity related to the surgical management of pediatric fourth ventricle tumors. METHODS All patients referred to the authors' institution with posterior fossa tumors from 2002 to 2018 inclusive were screened to include only true fourth ventricle tumors. Preoperative imaging and clinical notes were reviewed to extract data on presenting symptoms; surgical episodes, techniques, and adjuncts; tumor histology; and postoperative complications. RESULTS Three hundred fifty-four children with posterior fossa tumors were treated during the study period; of these, 185 tumors were in the fourth ventricle, and 167 fourth ventricle tumors with full data sets were included in this analysis. One hundred patients were male (mean age ± SD, 5.98 ± 4.12 years). The most common presenting symptom was vomiting (63.5%). The most common tumor types, in order, were medulloblastoma (94 cases) > pilocytic astrocytoma (30 cases) > ependymoma (30 cases) > choroid plexus neoplasms (5 cases) > atypical teratoid/rhabdoid tumor (4 cases), with 4 miscellaneous lesions. Of the 67.1% of patients who presented with hydrocephalus, 45.5% had an external ventricular drain inserted (66.7% of these prior to tumor surgery, 56.9% frontal); these patients were more likely to undergo ventriculoperitoneal shunt (VPS) placement at a later date (p = 0.00673). Twenty-two had an endoscopic third ventriculostomy, of whom 8 later underwent VPS placement. Overall, 19.7% of patients had a VPS sited during treatment.Across the whole series, the transvermian approach was more frequent than the telovelar approach (64.1% vs 33.0%); however, the telovelar approach was significantly more common in the latter half of the series (p < 0.001). Gross-total resection was achieved in 70.7%. The most common postoperative deficit was cerebellar mutism syndrome (CMS; 28.7%), followed by new weakness (24.0%), cranial neuropathy (18.0%), and new gait abnormality/ataxia (12.6%). Use of intraoperative ultrasonography significantly reduced the incidence of CMS (p = 0.0365). There was no significant difference in the rate of CMS between telovelar or transvermian approaches (p = 0.745), and multivariate logistic regression modeling did not reveal any statistically significant relationships between CMS and surgical approach. CONCLUSIONS Surgical management of pediatric fourth ventricle tumors continues to evolve, and resection is increasingly performed through the telovelar route. CMS is enduringly the major postoperative complication in this patient population.
An assessment of poly (ADP‐ribose) polymerase‐1 role in normal and cancer cells

Poly (ADP‐ribose) polymerase (PARP) is a superfamily of 18 proteins characterized by the PARP homology domain, the catalytic domain. This catalytic domain helps in the ADP‐ribosylation of various acceptor proteins using nicotinamide adenine dinucleotide (NAD+) as a donor for ADP‐ribose. PARP‐1 and PARP‐2 carry out 80% of poly‐ADP‐ribosylation of cellular protein. Hence, their combined knockout results in embryonic lethality of mice. PARP‐1 consists of three major domains, namely, DNA binding domain, automodification domain, and a catalytic domain. These domains further consist of subdomains and motifs, which helps PARP‐1 in a diverse function. PARP‐1 is mainly involved in DNA damage detection and repair, but emerging evidence suggests its role in many other functions such as DNA synthesis, replication, apoptosis, necrosis, and cancer progression. Herein, we review the current state of the PARP‐1 role in DNA damage repair and other biological processes including epithelial to mesenchymal transition (EMT). We have also observed the role of PARP‐1 in modulating EMT regulators like E‐cadherin, Vimentin, Claudin‐1, Snail, Smad‐4, Twist‐1, and β‐catenin. Here, we have also attempted to relate the role of PARP‐1 in EMT of cancer cells.
Relation between Mother’s Taekyo, Prenatal and Postpartum Depression, and Infant’s Temperament and Colic: A Longitudinal Prospective Approach

This longitudinal cohort correlational study aimed to confirm the relation among taekyo or traditional prenatal practice, prenatal depression, postpartum depression, maternal–fetal interaction, and infant temperament and colic using a prospective design. We recruited 212 women 16–20 weeks pregnant from July 2017 to September 2018; they were followed up until six months postpartum. Data from 97 participants were used in the final analysis. We used the Edinburgh Postnatal Depression Scale, Cranley’s Maternal–Fetal Attachment Scale, and What My Baby Is Like as measurement tools. We observed a significant correlation between prenatal maternal depression in the first to third trimesters and 6–8 weeks and six months postpartum. In addition, infant temperament at six months old showed a significant negative correlation with prenatal and postpartum depression: the higher the prenatal and postpartum depression level, the more difficult the infant’s temperament. Taekyo practice was significantly related to maternal–fetal attachment (r = 0.45−0.68, p < 0.001). Difficult infants showed more colic episodes than any other type of infant (χ2 = 18.18, p < 0.001). Prenatal and postnatal maternal depression affected infants’ temperament and colic episodes. The management of mothers’ mental health before and after pregnancy is important for infants’ and mothers’ health.
Use of Sublingual Immunotherapy for Aeroallergens in Children with Asthma

Asthma is a heterogeneous disease that in children is often allergen-driven with a type 2 inflammation. Sublingual immunotherapy represents an important progress in the use of personalized medicine in children with allergic asthma. It is a viable option for house dust mite-driven asthma and in subjects with the asthma associated with allergic rhinitis. The use and indications for isolated asthma caused by other allergens are still controversial owing to heterogeneity of commercially available products and methodological limitations of studies in children. Nevertheless, most studies and meta-analyses found the efficacy of sublingual immunotherapy. Sublingual immunotherapy is safe but cannot be recommended in children with uncontrolled asthma.
Social media and vaccine hesitancy

Background Understanding the threat posed by anti-vaccination efforts on social media is critically important with the forth coming need for world wide COVID-19 vaccination programs. We globally evaluate the effect of social media and online foreign disinformation campaigns on vaccination rates and attitudes towards vaccine safety. Methods Weuse a large-n cross-country regression framework to evaluate the effect ofsocial media on vaccine hesitancy globally. To do so, we operationalize social media usage in two dimensions: the use of it by the public to organize action(using Digital Society Project indicators), and the level of negative lyoriented discourse about vaccines on social media (using a data set of all geocoded tweets in the world from 2018-2019). In addition, we measure the level of foreign-sourced coordinated disinformation operations on social media ineach country (using Digital Society Project indicators). The outcome of vaccine hesitancy is measured in two ways. First, we use polls of what proportion ofthe public per country feels vaccines are unsafe (using Wellcome Global Monitor indicators for 137 countries). Second, we use annual data of actual vaccination rates from the WHO for 166 countries. Results We found the use of social media to organise offline action to be highly predictive of the belief that vaccinations are unsafe, with such beliefs mounting as more organisation occurs on social media. In addition, the prevalence of foreign disinformation is highly statistically and substantively significant in predicting a drop in mean vaccination coverage over time. A 1-point shift upwards in the 5-point disinformation scale is associated with a 2-percentage point drop in mean vaccination coverage year over year. We also found support for the connection of foreign disinformation with negative social media activity about vaccination. The substantive effect of foreign disinformation is to increase the number of negative vaccine tweets by 15% for the median country. Conclusion There is a significant relationship between organisation on social media and public doubts of vaccine safety. In addition, there is a substantial relationship between foreign disinformation campaigns and declining vaccination coverage.
Olive leaf extract attenuates adriamycin‐induced focal segmental glomerulosclerosis in spontaneously hypertensive rats via suppression of oxidative stress, hyperlipidemia, and fibrosis

Olive (Olea europaea L.) leaf extract (OLE) possesses powerful antioxidant, antihyperlipidemic, and anti‐inflammatory properties. The aim was to investigated the effects of OLE on the hyperlipidemia, antioxidant defense, heme oxygenase/biliverdin reductase (HO/BVR) pathway, inflammation, and fibrosis in spontaneously hypertensive rats with focal segmental glomerulosclerosis (FSGS, a progressive form of chronic kidney disease) induced by adriamycin (2 mg/kg, i.v., twice in a 21‐day period). Daily treatment of OLE (80 mg/kg, p.o.) for 6 weeks suppressed protein oxidation and lipid peroxidation (p < .01 and p < .001, respectively), significantly increased antioxidant enzymes activities and normalized antioxidant capacity, leading to the improvement of antioxidant defense independently of the HO/BVR pathway. Furthermore, the values of triglycerides (p < .01), total, and low‐density lipoprotein cholesterol (p < .05, both) were improved by OLE. OLE strongly prevented glomerulosclerosis, interstitial inflammation, and fibrosis (renal injury score, FSGS: 8 ± 0.45 vs. FSGS+OLE: 4.20 ± 1.07; p < .01), as evidenced by normalized fibronectin content (p < .001), suppressed interstitial inflammatory cells infiltration and collagen deposition, without changing cytokines expressions. OLE decreased blood pressure with a tendency to reduce urine albumin loss. These data suggest that OLE may be effective in slowing down the progression of FSGS.
Electrocardiographic findings at presentation and clinical outcome in patients with SARS-CoV-2 infection

Abstract Aims The main severe complications of SARS-CoV-2 infection are pneumonia and respiratory distress syndrome. Recent studies, however, reported that cardiac injury, as assessed by troponin levels, is associated with a worse outcome in these patients. No study hitherto assessed whether the simple standard electrocardiogram (ECG) may be helpful for risk stratification in these patients. Methods and results We studied 324 consecutive patients admitted to our Emergency Department with a confirmed diagnosis of SARS-CoV-2 infection. Standard 12-lead ECG recorded on admission was assessed for cardiac rhythm and rate, atrioventricular and intraventricular conduction, abnormal Q/QS wave, ST segment and T wave changes, corrected QT interval, and tachyarrhythmias. At a mean follow-up of 31 ± 11 days, 44 deaths occurred (13.6%). Most ECG variables were significantly associated with mortality, including atrial fibrillation (P = 0.002), increasing heart rate (P = 0.002), presence of left bundle branch block (LBBB; P < 0.001), QRS duration (P <0 .001), a QRS duration of ≥110 ms (P < 0.001), ST segment depression (P < 0.001), abnormal Q/QS wave (P = 0.034), premature ventricular complexes (PVCs; P = 0.051), and presence of any ECG abnormality [hazard ratio (HR) 4.58; 95% confidence interval (CI) 2.40–8.76; P < 0.001]. At multivariable analysis, QRS duration (P = 0.002), QRS duration ≥110 ms (P = 0.03), LBBB (P = 0.014) and presence of any ECG abnormality (P = 0.04) maintained a significant independent association with mortality. Conclusion Our data show that standard ECG can be helpful for an initial risk stratification of patients admitted for SARS-CoV-2 infectious disease.
Path differential-informed stratified MCMC and adaptive forward path sampling

Markov Chain Monte Carlo (MCMC) rendering is extensively studied, yet it remains largely unused in practice. We propose solutions to several practicability issues, opening up path space MCMC to become an adaptive sampling framework around established Monte Carlo (MC) techniques. We address non-uniform image quality by deriving an analytic target function for imagespace sample stratification. The function is based on a novel connection between variance and path differentials, allowing analytic variance estimates for MC samples, with potential uses in other adaptive algorithms outside MCMC. We simplify these estimates down to simple expressions using only quantities known in any MC renderer. We also address the issue that most existing MCMC renderers rely on bi-directional path tracing and reciprocal transport, which can be too costly and/or too complex in practice. Instead, we apply our theoretical framework to optimize an adaptive MCMC algorithm that only uses forward path construction. Notably, we construct our algorithm by adapting (with minimal changes) a full-featured path tracer into a single-path state space Markov Chain, bridging another gap between MCMC and existing MC techniques.
Efectos de la imagen universitaria sobre la identificación y la lealtad: existen diferencias siginificativas entre estudiantes y egresados

The aim of this research is to analyse the existence of significant differences between students and graduates regarding the positive effect of image on identification and loyalty. The data were obtained from an online survey. The data was processed using the structural equations technique (PLS-SEM). The findings show that there are significant differences in the positive effect of image on identification and loyalty, with the effect being more intense in graduates than in students. key words: image; identification; loyalty: multigroup analysis.
Disrupted topological properties of functional networks in epileptic children with generalized tonic‐clonic seizures

Generalized tonic‐clonic seizure (GTCS) is a condition that is characterized by generalized spike‐wave discharge in bilateral cerebral hemispheres during the seizure. Although previous neuroimaging studies revealed functional abnormalities in the brain activities of children with GTCS, the topological alterations in whole‐brain networks remain poorly understood.
Growth Hormone-Releasing Hormone in Lung Physiology and Pulmonary Disease

Growth hormone-releasing hormone (GHRH) is secreted primarily from the hypothalamus, but other tissues, including the lungs, produce it locally. GHRH stimulates the release and secretion of growth hormone (GH) by the pituitary and regulates the production of GH and hepatic insulin-like growth factor-1 (IGF-1). Pituitary-type GHRH-receptors (GHRH-R) are expressed in human lungs, indicating that GHRH or GH could participate in lung development, growth, and repair. GHRH-R antagonists (i.e., synthetic peptides), which we have tested in various models, exert growth-inhibitory effects in lung cancer cells in vitro and in vivo in addition to having anti-inflammatory, anti-oxidative, and pro-apoptotic effects. One antagonist of the GHRH-R used in recent studies reviewed here, MIA-602, lessens both inflammation and fibrosis in a mouse model of bleomycin lung injury. GHRH and its peptide agonists regulate the proliferation of fibroblasts through the modulation of extracellular signal-regulated kinase (ERK) and Akt pathways. In addition to downregulating GH and IGF-1, GHRH-R antagonist MIA-602 inhibits signaling pathways relevant to inflammation, including p21-activated kinase 1-signal transducer and activator of transcription 3/nuclear factor-kappa B (PAK1-STAT3/NF-κB and ERK). MIA-602 induces fibroblast apoptosis in a dose-dependent manner, which is an effect that is likely important in antifibrotic actions. Taken together, the novel data reviewed here show that GHRH is an important peptide that participates in lung homeostasis, inflammation, wound healing, and cancer; and GHRH-R antagonists may have therapeutic potential in lung diseases.
Development of novel models to investigate mutant p53 functions in pancreatic cancer and determinants of deregulated expression

Tumour suppressor p53 is mutated in 50-70% of pancreatic cancers (PDACs) and might modulate the biology of the disease. To investigate its function, we used a novel double recombinase (Flp/Cre) system allowing sequential activation of the oncogene KrasG12D and p53R172. We provide evidence that p53R172H is linked to proliferation and migration in vitro. p53 mutant is destabilized by HDAC inhibitors. This is due to a transcriptional mechanism involving the establishing of repressive histon marks.
Adaptability of Bt and NBt Cotton Hybrids in Different Locations in Central and Southern India

Cotton, white gold rules the world of textile moreover it is unchallenged as a natural textile fibre, despite the advent of a multitude of other fibres. It is an important fibre and food crop of nearly 100 countries with China, India, United States, Pakistan and Brazil being five of the largest producers of cotton. Since the discovery of the Mohen-jodaro relics the history of cotton and cotton manufacture came to be treated as beginning from times of the ancient Indus valley civilization, which flourished in India about 5000 years ago.
The Ionophores CCCP and Gramicidin but Not Nigericin Inhibit Trypanosoma brucei Aquaglyceroporins at Neutral pH

Human African trypanosomiasis (HAT) is caused by Trypanosoma brucei parasites. The T. brucei aquaglyceroporin isoform 2, TbAQP2, has been linked to the uptake of pentamidine. Negative membrane potentials and transmembrane pH gradients were suggested to promote transport of the dicationic antitrypanosomal drug. Application of ionophores to trypanosomes further hinted at direct inhibition of TbAQP2 by carbonyl cyanide m-chlorophenyl hydrazone (CCCP). Here, we tested for direct effects of three classical ionophores (CCCP, nigericin, gramicidin) on the functionality of TbAQP2 and the related TbAQP3 at conditions that are independent from the membrane potential or a proton gradient. We expressed TbAQP2 and TbAQP3 in yeast, and determined permeability of uncharged glycerol at neutral pH using stopped-flow light scattering. The mobile proton carrier CCCP directly inhibited TbAQP2 glycerol permeability at an IC50 of 2 µM, and TbAQP3 to a much lesser extent (IC50 around 1 mM) likely due to different selectivity filter layouts. Nigericin, another mobile carrier, left both isoforms unaffected. The membrane-integral pore-forming gramicidin evenly inhibited TbAQP2 and TbAQP2 in the double-digit micromolar range. Our data exemplify the need for suitable controls to detect unwanted ionophore side effects even when used at concentrations that are typically recommended to disturb the transmembrane ion distribution.
Prediction of severity and subtype of fibrosing disease using model informed by inflammation and extracellular matrix gene index

Fibrosis is a chronic disease with heterogeneous clinical presentation, rate of progression, and occurrence of comorbidities. Systemic sclerosis (scleroderma, SSc) is a rare rheumatic autoimmune disease that encompasses several aspects of fibrosis, including highly variable fibrotic manifestation and rate of progression. The development of effective treatments is limited by these variabilities. The fibrotic response is characterized by both chronic inflammation and extracellular remodeling. Therefore, there is a need for improved understanding of which inflammation-related genes contribute to the ongoing turnover of extracellular matrix that accompanies disease. We have developed a multi-tiered method using Naïve Bayes modeling that is capable of predicting level of disease and clinical assessment of patients based on expression of a curated 60-gene panel that profiles inflammation and extracellular matrix production in the fibrotic disease state. Our novel modeling design, incorporating global and parametric-based methods, was highly accurate in distinguishing between severity groups, highlighting the importance of these genes in disease. We refined this gene set to a 12-gene index that can accurately identify SSc patient disease state subsets and informs knowledge of the central regulatory pathways in disease progression.