Miracle-dz/UniFAR-FTUs huggingface dataset:
Molecular Pattern and Density of Axons in the Long Head of the Biceps Tendon and the Superior Labrum

The type II superior labrum anterior to posterior (SLAP) repair is a viable option in young and demanding patients, although a prolonged period of pain after surgery is described in the literature. The reason for this fact remains unknown. Thus, the purpose of this study was to investigate the molecular pattern of the biceps tendon anchor, where the sutures for repair are placed. The long head of the biceps tendon (LHBT), including the superior labrum, was dissected in the setting of reverse total shoulder arthroplasty. Immunohistochemical staining was performed using neurofilament (NF) and protein gene product (PGP) 9.5 as general markers for axons and calcitonin gene-related peptide (CGRP) and substance P for nociceptive transmission. A quantitative assessment was performed according to the two regions of interest (ROIs), i.e., the anterosuperior (ROI I) and the posterosuperior labrum (ROI II). Eleven LHBTs with a mean age of 73 years (range: 66–87 years) were harvested intraoperatively. Six LHBTs were gained in osteoarthrosis and five in fractures. We found an inhomogeneous distribution of axons in the anterosuperior and posterosuperior parts of the labrum in all the specimens irrespective of the age, gender, and baseline situation. There was a significantly higher number (p < 0.01) as well as density (p < 0.001) of NF-positive axons in ROI I compared to ROI II. Nociceptive fibers were always found along the NF-positive axons. Thus, our results indicate that the biceps tendon anchor itself is a highly innervated region comprising different nerve qualities. The anterosuperior labrum contains a higher absolute number and density of axons compared to the posterosuperior parts. Furthermore, we were able to prove the presence of nociceptive fibers in the superior labrum. The results obtained in this study could contribute to the variability of pain after SLAP repair.
Animal Models of Chronic Cerebral Hypoperfusion: From Mouse to Primate

Vascular cognitive impairment (VCI) or vascular dementia occurs as a result of brain ischemia and represents the second most common type of dementia after Alzheimer’s disease. To explore the underlying mechanisms of VCI, several animal models of chronic cerebral hypoperfusion have been developed in rats, mice, and primates. We established a mouse model of chronic cerebral hypoperfusion by narrowing the bilateral common carotid arteries with microcoils, eventually resulting in hippocampal atrophy. In addition, a mouse model of white matter infarct-related damage with cognitive and motor dysfunction has also been established by asymmetric common carotid artery surgery. Although most experiments studying chronic cerebral hypoperfusion have been performed in rodents because of the ease of handling and greater ethical acceptability, non-human primates appear to represent the best model for the study of VCI, due to their similarities in much larger white matter volume and amyloid β depositions like humans. Therefore, we also recently developed a baboon model of VCI through three-vessel occlusion (both the internal carotid arteries and the left vertebral artery). In this review, several animal models of chronic cerebral hypoperfusion, from mouse to primate, are extensively discussed to aid in better understanding of pathophysiology of VCI.
New Pre-reacted Glass Containing Dental Composites (giomers) with Improved Fluoride Release and Biocompatibility

The aim of the present work was to prepare a series of novel restorative giomers and investigate the morphology, the physico-chemical properties (residual monomer, fluoride release), and the cytotoxicity of the new materials. The experimental giomers were prepared as light-cured pastes by blending different resin matrices comprising aromatic/aliphatic/urethane (di) methacrylates, with hybrid fillers containing pre-reacted glasses (PRGs), a radiopaque glass, and nano fluorhydroxyapatite. Polyalkenoic acids based on acrylic acid/itaconic acid/N-acryloyl -L-leucine modified or not with methacrylic groups, together with a superficially active glass, were used to prepare the PRGs. The fluoride ion release of the experimental giomers was investigated within a period of 60 days of storage in bidistilled water while using a fluoride ion selective electrode. Beautifil II commercial product was used as a reference. Cell cytotoxicity tests were done in vitro, in accordance with ISO 10993-122012 proceedings. Human dermal fibroblasts and umbilical endothelial vein cultures were used. The values that were obtained for cumulative fluoride release for all experimental giomers were higher than for the Beautifil II product, being more than twice the ones that were obtained for the commercial product after 60 days of storage in bidistilled water. The experimental biomaterials showed similar and/or better results when compared to the commercial one; this effect was maintained in all tested conditions.
Activating Mutations of the G-protein Subunit α 11 Interdomain Interface Cause Autosomal Dominant Hypocalcemia Type 2

Abstract Context Autosomal dominant hypocalcemia types 1 and 2 (ADH1 and ADH2) are caused by germline gain-of-function mutations of the calcium-sensing receptor (CaSR) and its signaling partner, the G-protein subunit α 11 (Gα 11), respectively. More than 70 different gain-of-function CaSR mutations, but only 6 different gain-of-function Gα 11 mutations are reported to date. Methods We ascertained 2 additional ADH families and investigated them for CaSR and Gα 11 mutations. The effects of identified variants on CaSR signaling were evaluated by transiently transfecting wild-type (WT) and variant expression constructs into HEK293 cells stably expressing CaSR (HEK-CaSR), and measuring intracellular calcium (Ca2+i) and MAPK responses following stimulation with extracellular calcium (Ca2+e). Results CaSR variants were not found, but 2 novel heterozygous germline Gα 11 variants, p.Gly66Ser and p.Arg149His, were identified. Homology modeling of these revealed that the Gly66 and Arg149 residues are located at the interface between the Gα 11 helical and GTPase domains, which is involved in guanine nucleotide binding, and this is the site of 3 other reported ADH2 mutations. The Ca2+i and MAPK responses of cells expressing the variant Ser66 or His149 Gα 11 proteins were similar to WT cells at low Ca2+e, but significantly increased in a dose-dependent manner following Ca2+e stimulation, thereby indicating that the p.Gly66Ser and p.Arg149His variants represent pathogenic gain-of-function Gα 11 mutations. Treatment of Ser66- and His149-Gα 11 expressing cells with the CaSR negative allosteric modulator NPS 2143 normalized Ca2+i and MAPK responses. Conclusion Two novel ADH2-causing mutations that highlight the Gα 11 interdomain interface as a hotspot for gain-of-function Gα 11 mutations have been identified.
Human matriptase/ST 14 proteolytically cleaves H7N9 hemagglutinin and facilitates the activation of influenza A/Shanghai/2/2013 virus in cell culture

Influenza is a zoonotic disease that infects millions of people each year resulting in hundreds of thousands of deaths, and in turn devastating pandemics. Influenza is caused by influenza viruses, including influenza A virus (IAV). There are many subtypes of IAV but only a few seem to be able to adapt to humans and to cause disease. In 2013, an H7N9 IAV subtype emerged in China that does not cause clinical symptoms in its chicken host but leads to severe infections when transmitted into humans. Since 2013, there have been six epidemic waves of H7N9 with 1567 laboratory‐confirmed human infections and 615 deaths. Pathogenicity of IAV is complex, but a crucial feature contributing to virulence is the activation of the hemagglutinin (HA) fusion protein by host proteases that triggers membrane fusion and leads to subsequent virus propagation.
Coping with Cybervictimization: The Role of Direct Confrontation and Resilience on Adolescent Wellbeing

Background. Recent studies have consistently identified the negative consequences of cyberbullying on adolescent mental health. Nevertheless, not all cybervictims are alike, and in the last few years some evidence has appeared indicating that faced with cyberbullying, victims may manifest different emotional outcomes. In this study, we explored whether cybervictim resilience fully or partially mediates the effects of cybervictimization and whether a confrontational coping strategy impacts emotional symptoms. Methods. The study was carried out with a sample of 474 high school students equally distributed between males and females. Data were collected using a questionnaire comprising four measures assessing cybervictimization, direct confrontation coping strategy, resilience and emotional symptoms. Results. Structural equation modelling indicated that the effects of cybervictimization and confrontational coping strategy on emotional symptoms were mediated by resilience, with cybervictimization showing a positive effect while direct confrontation a negative effect. Cybervictimization also showed a positive direct effect on emotional symptoms. Conclusions. These results are presented in light of their implications for designing effective interventions able to protect and promote adolescents’ psychological wellbeing.
Role of Ceramidases in Sphingolipid Metabolism and Human Diseases

Human pathologies such as Alzheimer’s disease, type 2 diabetes-induced insulin resistance, cancer, and cardiovascular diseases have altered lipid homeostasis. Among these imbalanced lipids, the bioactive sphingolipids ceramide and sphingosine-1 phosphate (S1P) are pivotal in the pathophysiology of these diseases. Several enzymes within the sphingolipid pathway contribute to the homeostasis of ceramide and S1P. Ceramidase is key in the degradation of ceramide into sphingosine and free fatty acids. In humans, five different ceramidases are known—acid ceramidase, neutral ceramidase, and alkaline ceramidase 1, 2, and 3—which are encoded by five different genes (ASAH1, ASAH2, ACER1, ACER2, and ACER3, respectively). Notably, the neutral ceramidase N-acylsphingosine amidohydrolase 2 (ASAH2) shows considerable differences between humans and animals in terms of tissue expression levels. Besides, the subcellular localization of ASAH2 remains controversial. In this review, we sum up the results obtained for identifying gene divergence, structure, subcellular localization, and manipulating factors and address the role of ASAH2 along with other ceramidases in human diseases.
Environmental Toxicology and Chemistry

Mortality of brook trout Salvelinus fontinalis and water chemistry were characterized in 6 headwater streams in the western Adirondacks of New York during spring 2015, 2016, and 2017 and compared with results from analogous tests done between 1980 and 2003 in many of the same streams, to assess temporal changes in toxicity and inorganic monomeric aluminum (Ali) concentrations, and the role of Ali exposure duration on brook trout survival. The Ali concentrations of 2 and 4 μmol L corresponded to low‐to‐moderate and high mortality thresholds, but prolonged exposure to ≥1 μmol Ali L also produced mortality. The variability, mean, and highest Ali concentrations in Buck Creek year round, and in several other streams during spring, have decreased significantly over the past 3 decades. Logistic models indicate that Ali surpassed highly toxic concentrations in Buck Creek for 3 to 4mo annually during 2001 to 2003 and for 2 to 3 wk annually during 2015 to 2017. The loss of extremely high Ali episodes indicates that toxicity has declined markedly between the 1989 to 1990, 2001 to 2003, and 2015 to 2017 test periods, yet Ali concentrations can still cause moderate‐to‐high and complete (100%) mortality. The logistic models illustrate how mortality of brook trout in several Adirondack streams likely decreased in response to the 1990 Amendments to the United States' Clean Air Act (which decreased acidity, Ali concentrations, and duration of toxic episodes) and offer a means to predict how changes in US regulations that limit emissions of NOx and SOx (and N and S deposition loads) could affect fish survival and stream ecosystems in this region and across the Northeast. Environ Toxicol Chem 2020;39:623–636. © 2019 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals, Inc. on behalf of SETAC.
Human Milk Omega-3 Fatty Acid Composition Is Associated with Infant Temperament

There is growing evidence that omega-3 (n-3) polyunsaturated fatty-acids (PUFAs) are important for the brain development in childhood and are necessary for an optimal health in adults. However, there have been no studies examining how the n-3 PUFA composition of human milk influences infant behavior or temperament. To fill this knowledge gap, 52 breastfeeding mothers provided milk samples at 3 months postpartum and completed the Infant Behavior Questionnaire (IBQ-R), a widely used parent-report measure of infant temperament. Milk was assessed for n-3 PUFAs and omega-6 (n-6) PUFAs using gas-liquid chromatography. The total fat and the ratio of n-6/n-3 fatty acids in milk were also examined. Linear regression models revealed that infants whose mothers’ milk was richer in n-3 PUFAs had lower scores on the negative affectivity domain of the IBQ-R, a component of temperament associated with a risk for internalizing disorders later in life. These associations remained statistically significant after considering covariates, including maternal age, marital status, and infant birth weight. The n-6 PUFAs, n-6/n-3 ratio, and total fat of milk were not associated with infant temperament. These results suggest that mothers may have the ability to shape the behavior of their offspring by adjusting the n-3 PUFA composition of their milk.
Caring for Tuberculosis Patients: Understanding the Plight of Nurses at a Regional Hospital in Limpopo Province, South Africa

Tuberculosis (TB) is a disease which is caused by a relatively large, non-motile, rod-shaped pathogen called Mycobacterium tuberculosis. TB is a major cause of illness and death worldwide, especially in Asia and Africa. Despite the fact that TB is a curable illness, the tragedy is that TB remains the biggest killer in the world as a single pathogen. The aim of this study was to determine the experiences of nurses caring for TB patients at a regional hospital in Limpopo Province, South Africa. Qualitative, exploratory, and descriptive designs were used. A non-probability purposive sampling method was used to select the participants. The personal experiences of six nurses with more than five years’ experience caring for TB patients at a regional hospital were explored, and it was guided by data saturation. Data were collected through in-depth individual interviews. Data were analyzed using Colaizzi’s method. Trustworthiness was ensured and ethical considerations were observed in this study. The research findings revealed six major themes from the raw data: challenges of the working environment, problems impacting on the quality of nursing care, fear, anxiety, stress and risk of contracting infection, nurses’ perceptions towards patients, support structure available in the hospital, and support needs for the nurses. Therefore, there is an urgent need to address the challenges experienced by nurses caring for communicable diseases through provision of a positive practice work environment.
Alternative Strategies to Inhibit Tumor Vascularization

Endothelial cells present in tumors show different origin, phenotype, and genotype with respect to the normal counterpart. Various mechanisms of intra-tumor vasculogenesis sustain the complexity of tumor vasculature, which can be further modified by signals deriving from the tumor microenvironment. As a result, resistance to anti-VEGF therapy and activation of compensatory pathways remain a challenge in the treatment of cancer patients, revealing the need to explore alternative strategies to the classical anti-angiogenic drugs. In this review, we will describe some alternative strategies to inhibit tumor vascularization, including targeting of antigens and signaling pathways overexpressed by tumor endothelial cells, the development of endothelial vaccinations, and the use of extracellular vesicles. In addition, anti-angiogenic drugs with normalizing effects on tumor vessels will be discussed. Finally, we will present the concept of endothelial demesenchymalization as an alternative approach to restore normal endothelial cell phenotype.
The human protein haptoglobin inhibits IsdH-mediated heme-sequestering by Staphylococcus aureus

Iron is an essential nutrient for all living organisms. To acquire iron, many pathogens have developed elaborate systems to steal it from their hosts. The iron acquisition system in the opportunistic pathogen Staphylococcus aureus comprises nine proteins, called iron-regulated surface determinants (Isds). The Isd components enable S. aureus to extract heme from hemoglobin (Hb), transport it into the bacterial cytoplasm, and ultimately release iron from the porphyrin ring. IsdB and IsdH act as hemoglobin receptors and are known to actively extract heme from extracellular Hb. To limit microbial pathogenicity during infection, host organisms attempt to restrict the availability of nutrient metals at the host–pathogen interface. The human acute phase protein haptoglobin (Hp) protects the host from oxidative damage by clearing hemoglobin that has leaked from red blood cells and also restricts the availability of extracellular Hb-bound iron to invading pathogens. To investigate whether Hp serves an additional role in nutritional immunity through a direct inhibition of IsdH-mediated iron acquisition, here we measured heme extraction from the Hp–Hb complex by UV-visible spectroscopy and determined the crystal structure of the Hp–Hb–IsdH complex at 2.9 Å resolution. We found that Hp strongly inhibits IsdH-mediated heme extraction and that Hp binding prevents local unfolding of the Hb heme pocket, leaving IsdH unable to wrest the heme from Hb. Furthermore, we noted that the Hp–Hb binding appears to trap IsdH in an initial state before heme transfer. Our findings provide insights into Hp-mediated IsdH inhibition and the dynamics of IsdH-mediated heme extraction.
Changing Epidemiology and Predisposing Factors for Invasive Pneumococcal Disease at Two Australian Tertiary Hospitals.

BACKGROUND Invasive pneumococcal disease (IPD) is associated with significant morbidity and mortality in children. Universal pneumococcal conjugate vaccination has changed the epidemiology of IPD. In vaccinated children, IPD can be a marker of an underlying immunodeficiency. METHODS This is a retrospective audit of children younger than 18 years with IPD admitted to 2 tertiary pediatric hospitals in Australia between 2011 and 2017. Data on predisposing conditions, immunologic evaluation, pneumococcal serotype, antibiotic susceptibility and treatment were collected. RESULTS During the 7-year period, there were 131 presentations with IPD in 127 children; 3 children had recurrent IPD. Patients presented with sepsis (41%), empyema (29%), meningitis (18%), mastoiditis (12%), pneumonia (10%) and septic arthritis (4%). In 19 (15%) presentations, risk factors for IPD were present, including malignancy, hematologic disorder, chronic liver disease, chronic kidney disease and cochlear implant. Pneumococcal serotypes were determined in 78/131 (60%) of presentations: the most frequent serotypes were 19A (19%), 3 (13%), 7F (10%) and 19F (8%) and non-vaccine serotypes 22F (8%), 35B (6%), 15A (4%) and 38 (4%). Overall, 11% of isolates were non-susceptible to ceftriaxone. Only 36 patients (32%) had an immunologic evaluation, and 4 patients had proven or probable immunodeficiency. CONCLUSION Although pneumococcal conjugate vaccine serotypes 19A, 3, 19F and 7F remain frequent causes of IPD, non-vaccine serotypes are emerging. Our data support vancomycin treatment for children with pneumococcal meningitis given 11% of our isolates were not susceptible to ceftriaxone. It is important to consider underlying conditions predisposing to IPD in a population with high rates of pneumococcal vaccination.
Association of Iron Status and Intake During Pregnancy with Neuropsychological Outcomes in Children Aged 7 Years: The Prospective Birth Cohort Infancia y Medio Ambiente (INMA) Study

Early iron status plays an important role in prenatal neurodevelopment. Iron deficiency and high iron status have been related to alterations in child cognitive development; however, there are no data about iron intake during pregnancy with other environmental factors in relation to long term cognitive functioning of children. The aim of this study is to assess the relationship between maternal iron status and iron intake during pregnancy and child neuropsychological outcomes at 7 years of age. We used data from the INMA Cohort population-based study. Iron status during pregnancy was assessed according to serum ferritin levels, and iron intake was assessed with food frequency questionnaires. Working memory, attention, and executive function were assessed in children at 7 years old with the N-Back task, Attention Network Task, and the Trail Making Test, respectively. The results show that, after controlling for potential confounders, normal maternal serum ferritin levels (from 12 mg/L to 60 mg/L) and iron intake (from 14.5 mg/day to 30.0 mg/day), respectively, were related to better scores in working memory and executive functioning in offspring. Since these functions have been associated with better academic performance and adaptation to the environment, maintaining a good state of maternal iron from the beginning of pregnancy could be a valuable strategy for the community.
Microalgae in Food-Energy-Water Nexus: A Review on Progress of Forward Osmosis Applications

Nowadays the world is facing vulnerability problems related to food, energy and water demands. The challenges in those subsystems are intertwined and thus require inter-discipline approaches to address them. Bioresources offer promising solutions of the dilemma. Microalgae biomass is expected to become a superfood and a favorable energy feedstock and assist in supplying clean water and treat wastewater. Efficient mass production of microalgae, both during upstream and downstream processes, is thus a key process for providing high quality and affordable microalgae biomass. This paper covers recent progress in microalgae harvesting and dewatering by using osmotic driven membrane process, i.e., forward osmosis. Critical factors during forward osmosis process for microalgae harvesting and dewatering are discussed. Finally, perspective on further research directions and implementation scenarios of the forward osmosis are also provided.