Miracle-dz/UniFAR-FTUs huggingface dataset:
Exploring healthcare professionals’ knowledge, attitudes and experiences of shared decision making in rheumatology

Objectives To explore physicians’ and nurses’ knowledge, attitudes and experiences of shared decision making (SDM) in rheumatology, to identify barriers and facilitators to SDM, and to examine whether physicians’ and nurses’ perspectives of SDM differ. Methods A cross-sectional, exploratory, online survey was used. Besides demographic characteristics, healthcare professionals’ knowledge, attitudes and experiences of SDM in rheumatology were assessed. Barriers and facilitators to SDM were identified from healthcare professionals’ answers. Descriptive statistics were computed and differences between physicians’ and nurses’ perspectives of SDM were examined with a t-test or Fisher’s exact test, as appropriate. Results Between April and June 2019, 77 physicians and 70 nurses completed the survey. Although most healthcare professionals lacked a full conceptual understanding of SDM, almost all physicians (92%) and all nurses had a (very) positive attitude toward SDM, which was most frequently motivated by the belief that SDM improves patients’ treatment adherence. The majority (>50%) of healthcare professionals experienced problems with the application of SDM in clinical practice, mostly related to time constraints. Other important barriers were the incompatibility of SDM with clinical practice guidelines and beliefs that patients do not prefer to be involved in decision making or are not able to take an active role. Modest differences between physicians’ and nurses’ perspectives of SDM were found. Conclusions There is a clear need for education and training that equips and empowers healthcare professionals to apply SDM. Furthermore, the commitment of time, resources and financial support for national, regional and organisational initiatives is needed to make SDM in rheumatology a practical reality.
Integration of digital maxillary dental casts with 3D facial images in orthodontic patients.

OBJECTIVE To evaluate three-dimensional (3D) accuracy and reliability of nonradiographic dentofacial images integrated with a two-step method. METHODS 3D facial images, cone-beam computed tomography (CBCT) images and digital maxillary dental casts were obtained from 20 pre-orthodontic subjects. Digital dental casts were integrated into 3D facial images using a two-step method based on the anterior tooth area. 3D coordinate values of five dental landmarks were identified in both dentofacial images and CBCT images. The accuracy of the integration method was assessed with paired t-tests between dentofacial images and CBCT-based reference standards. Intraclass correlation coefficients (ICCs) were assessed for the reliability of dentofacial images and CBCT-based images. Analysis of variance and Kruskal-Wallis tests evaluated the accuracy of the method in different dimensions. RESULTS There was no statistical difference between dentofacial images and CBCT reference standards in both translational and rotational dimensions (P > .05). Translational mean absolute errors for full dentitions were within 0.42 mm and ICCs were over 0.998 in x, y, and z directions. Rotational mean absolute errors for full dentitions were within 0.92° and ICCs over 0.734 in pitch, yaw, and roll orientations. Integration errors were significantly greater in the first molar, z-translation, and pitch rotation (P < .05). CONCLUSIONS Integrating 3D dentofacial images with the two-step method is precise and acceptable for clinical diagnostics and scientific purposes. Errors were greater in the molar region, z-translation, and pitch rotation.
Structure, Defects and Magnetism of Electrospun Hematite Nanofibers Silica-Coated by Atomic Layer Deposition.

: In the last years, hematite has been utilized in a plethora of applications. High aspect-ratio nanohematite and hematite/silica core-shell nanostructures are arousing a growing interest for applications exploiting their magnetic properties. Atomic layer deposition (ALD) is here utilized to produce SiO2-coated -Fe2O3 nanofibers (NFs) through two synthetic routes, viz. electrospinning/calcination/ALD or electrospinning/ALD/calcination. The number of ALD cycles (10-100) modulates the coating thickness, while the chosen route controls the final nanostructure. Porous and partially hollow NFs are produced. Their hierarchical structure, and the nature and density of the lattice defects and strain are characterized by combining electron microscopy, diffraction and spectroscopy techniques. The uncoated hematite NFs mostly have surface-related strain, attributed to oxygen vacancies/Fe2+ sites. ALD coating causes microstrain release and decrease of surface states. NFs calcined after ALD have extensive bulk strain, ascribed to the presence of dislocations throughout the volume of the NF- grains. Bulk strain determines the remanent magnetization, whereas both surface and bulk strain influence the coercive field and the thermal behavior across the Morin temperature, including the magnetic memory effect. To the best of the authors' knowledge, the correlation between lattice defects/strain and magnetic properties of SiO2-coated -Fe2O3 NFs has never been reported before.
Serum neurofilament light chain reflects inflammation-driven neurodegeneration and predicts delayed brain volume loss in early stage of multiple sclerosis

Background: Serum neurofilament light chain (sNfL) is a marker of neuroaxonal injury. There is a lack of studies investigating the dynamics of relationships between sNfL levels and radiological disease activity over long-term follow-up in multiple sclerosis (MS). Objectives: To investigate the relationship among repeated measures of sNfL, lesion burden accumulation, brain volume loss and clinical measures. Methods: We investigated 172 patients in the early stages of MS (McDonald 2017 criteria). Clinical exams were performed every 3 months and brain magnetic resonance imaging (MRI) scans were collected annually over 48 months. sNfL levels were measured in serum by Simoa assay at the time of treatment initiation and then annually over 36 months. Results: In repeated-measures analysis, considering all time points, we found a strong relationship between percentage changes of sNfL and lesion burden accumulation assessed by T1 lesion volume (p < 0.001) and T2 lesion number (p < 0.001). There was no relationship between percentage changes of sNfL and brain volume loss over 36 months (p > 0.1). Early sNfL levels were associated with delayed brain volume loss after 48 months (p < 0.001). Patients with No Evidence of Disease Activity (NEDA-3) status showed lower sNfL levels compared with active MS patients. Conclusions: sNfL is associated with ongoing neuroinflammation and predictive of future neurodegeneration in early MS.
Development of the Microbiota and Associations With Birth Mode, Diet, and Atopic Disorders in a Longitudinal Analysis of Stool Samples, Collected From Infancy Through Early Childhood.

BACKGROUND & AIMS Establishment of the gastrointestinal microbiota during infancy affects immune system development and oral tolerance induction. Perturbations in the microbiome during this period can contribute to development of immune-mediated diseases. We monitored microbiota maturation and associations with subsequent development of allergies in infants and children. METHODS We collected 1453 stool samples, at 5, 13, 21 and 31 weeks post-partum (infants), and once at school-age (6-11 years), from 440 children (49.3% girls, 24.8% born by caesarean section; all children except for 6 were breastfed for varying durations; median 40 weeks; interquartile range, 30-53 weeks). Microbiota were analyzed by amplicon sequencing. Children were followed through 3 years of age for development of atopic dermatitis; data on allergic sensitization and asthma were collected when children were school age. RESULTS Diversity of fecal microbiota, assessed by Shannon index, did not differ significantly among children from 5 through 13 weeks after birth, but thereafter gradually increased to 21 and 31 weeks. Most bacteria within the Bacteroidetes and Proteobacteria phyla were already present at 5 weeks after birth, whereas many bacteria of the Firmicutes phylum were acquired at later times in infancy. At school age, many new Actinobacteria, Firmicutes, and Bacteroidetes bacterial taxa emerged. The largest increase in microbial diversity occurred after 31 weeks. Vaginal, compared with cesarean section delivery, was most strongly associated with an enrichment of Bacteroides species at 5 weeks through 31 weeks. From 13 weeks onwards, diet became most important determinant of microbiota composition-cessation of breastfeeding, rather than solid food introduction, was associated with changes. For example, Bifidobacteria, staphylococci, and streptococci significantly decreased upon cessation of breastfeeding, whereas bacteria within the Lachnospiraceae family (Pseudobutyrivibrio, Lachnobacterium, Roseburia, and Blautia) increased. When we adjusted for confounding factors, we found fecal microbiota composition to be associated with development of atopic dermatitis, allergic sensitization, and asthma. Members of the Lachnospiraceae family, as well as the genera Faecalibacterium and Dialister, were associated with a reduced risk of atopy. CONCLUSIONS In a longitudinal study of fecal microbiota of children from 5 weeks through 6-11 years, we tracked changes in diversity and composition associated with the development of allergies and asthma.
Cross-sectional phenotyping of small airway dysfunction in preschool asthma using the impulse oscillometry system

Abstract Objective. Asthma is a chronic inflammatory airway disorder known to induce small airways dysfunction (SAD). It is important to develop tools to assess the presence and extent of SAD in daily clinical practice. An Impulse Oscillometry System (IOS) might detect SAD, but the validity of the underlying model (serial Resistive airway and Compliant tissue model: RC model) in diseased lungs remains questionable. Methods. Our objective was to evaluate the usefulness of parameters obtained from six electrical circuit models that were fitted to the measurements of impedance obtained with IOS in asthmatic children characterized by an abnormal lung function defined by an increased baseline interrupter resistance (Rint, z-score > +1.645). Results. The six models were tested in 102 asthmatic children (median age: 5.5 years). Two models allowed the description of 92/102 (90%) children: 74 by the extended RIC model (central and peripheral Resistance, Inertance and peripheral airway Compliance) and 18 by the Mead1969 model (extended RIC plus lung compliance). Thus, peripheral airway compliance and resistance were essential to describe lung function abnormalities of these asthmatic children. Parenchyma impairment (increased lung compliance) which was responsive to salbutamol was present in 18% of asthmatic children. After salbutamol, peripheral airway resistance decreased while peripheral airway compliance increased, arguing for asthma-related SAD. R5-20Hz independently correlated with the two latter parameters but was increased in two thirds of children with increased Rint only. Conclusion. Additional modeling of IOS results can be a reliable tool to assess the presence and extent of SAD in young asthmatic children.
Carcinoembryonic antigen‐specific, fluorescent image‐guided cytoreductive surgery with hyperthermic intraperitoneal chemotherapy for metastatic colorectal cancer

This multicentre pilot study investigated the role of peroperative carcinoembryonic antigen (CEA)‐specific fluorescence imaging during cytoreductive surgery–hyperthermic intraperitoneal chemotherapy surgery in peritoneal metastasized colorectal cancer. A correct change in peritoneal carcinomatosis index (PCI) owing to fluorescence imaging was seen in four of the 14 included patients. The use of SGM‐101 in patients with peritoneally metastasized colorectal carcinoma is feasible, and allows intraoperative detection of tumour deposits and alteration of the PCI. Augmented reality guidance
Orbitrap mass spectrometry for monitoring the ganglioside pattern in human cerebellum development and aging.

We have developed here a superior approach based on high resolution (HR) mass spectrometry (MS) for monitoring the changes occurring with development and aging in the composition and structure of cerebellar gangliosidome. The experiments were focused on the comparative screening and structural analysis of gangliosides expressed in fetal and aged cerebellum by Orbitrap MS with nanoelectrospray ionization (nanoESI) in the negative ion mode. The employed ultra-high resolution MS platform allowed the discrimination, without the need of previous separation, of 159 ions corresponding to 120 distinct species in the native ganglioside mixtures from fetal and aged cerebellar biopsies, many more than detected before, when MS platforms of lower resolution were employed. A number of gangliosides, in particular polysialylated belonging to GT, GQ, GP and GS classes, modified by O-fucosylation, O-acetylation or CH3 COO- were discovered here, for the first time in human cerebellum. These components, found differently expressed in fetal and aged tissues, indicated that the ganglioside profile in cerebellum is development stage- and age-specific. Following the fragmentation analysis by high energy collision-induced dissociation (HCD) tandem MS (MS/MS) we have also observed that the intimate structure of certain compounds has not changed during the development and aging of the brain, an aspect which could open new directions in the investigation of ganglioside biomarkers in cerebellar tissue.
Interspecies Transmission of Reassortant Swine Influenza A Virus Containing Genes from Swine Influenza A(H1N1)pdm09 and A(H1N2) Viruses

Influenza A(H1N1)pdm09 (pH1N1) virus has become established in swine in the United Kingdom and currently co-circulates with previously enzootic swine influenza A virus (IAV) strains, including avian-like H1N1 and human-like H1N2 viruses. During 2010, a swine influenza A reassortant virus, H1N2r, which caused mild clinical disease in pigs in the United Kingdom, was isolated. This reassortant virus has a novel gene constellation, incorporating the internal gene cassette of pH1N1-origin viruses and hemagglutinin and neuraminidase genes of swine IAV H1N2 origin. We investigated the pathogenesis and infection dynamics of the H1N2r isolate in pigs (the natural host) and in ferrets, which represent a human model of infection. Clinical and virologic parameters were mild in both species and both intraspecies and interspecies transmission was observed when initiated from either infected pigs or infected ferrets. This novel reassortant virus has zoonotic and reverse zoonotic potential, but no apparent increased virulence or transmissibility, in comparison to pH1N1 viruses.
The discovery and maturation of peptide biologics targeting the small G-protein Cdc42: A bioblockade for Ras-driven signaling

Aberrant Ras signaling drives 30% of cancers, and inhibition of the Rho family small GTPase signaling has been shown to combat Ras-driven cancers. Here, we present the discovery of a 16-mer cyclic peptide that binds to Cdc42 with nanomolar affinity. Affinity maturation of this sequence has produced a panel of derived candidates with increased affinity and modulated specificity for other closely-related small GTPases. The structure of the tightest binding peptide was solved by NMR, and its binding site on Cdc42 was determined. Addition of a cell-penetrating sequence allowed the peptides to access the cell interior and engage with their target(s), modulating signaling pathways. In Ras-driven cancer cell models, the peptides have an inhibitory effect on proliferation and show suppression of both invasion and motility. As such, they represent promising candidates for Rho-family small GTPase inhibitors and therapeutics targeting Ras-driven cancers. Our data add to the growing literature demonstrating that peptides are establishing their place in the biologics arm of drug discovery.
Angiopoietin 2 and Neuropeptide Y are Associated with Diabetic Kidney Disease in Type 1 Diabetes Mellitus

Abstract Background Serum angiopoietin 2 levels have been associated with endothelial dysfunction and diabetic kidney disease. Derangements in autonomous nervous system lead to increased production of vasoconstrictory and angiogenic mediators such as norepinephrine and neuropeptide Y and are associated with increased risk of microvascular complications. Aim To investigate associations between angiopoietin 2, neuropeptide Y and diabetic kidney disease in patients with type 1 diabetes mellitus. Methods 289 patients with type 1 diabetes mellitus duration > 1 year were included. Patients were stratified according to presence of diabetic nephropathy (macroalbuminuria, estimated glomerular filtration rate<60 ml/min/1.73 m2 or end-stage renal disease). Angiopoietin 2 was measured by Luminex technology. Neuropeptide Y was measured by ELISA. Results Patients with diabetic nephropathy had significantly increased levels of angiopoietin 2 (4020.5 (2172.4–5778.1) pg/ml vs. 2001.0 (1326.7–2862.7) pg/ml) and neuropeptide Y (18.22 (14.85–21.85) ng/ml vs. 12.91 (9.96–17.07) ng/ml). Higher levels of angiopoietin 2 and neuropeptide Y were observed also in patients with arterial hypertension. Angiopoietin 2 and neuropeptide Y correlated significantly (ρ=0.245, p<0.001). Both biomarkers were significant predictors of estimated glomerular filtration rate and diabetic nephropathy in univariate regression models. In the fully adjusted regression models and after application of a stepwise selection regression method, angiopoietin 2 demonstrated a stronger predictive power for diabetic nephropathy compared to neuropeptide Y. Conclusion Diabetic nephropathy is associated with increased serum concentrations of angiopoietin 2 (marker of endothelial dysfunction) and neuropeptide Y (marker of sympathetic activity) in type 1 diabetes. Angiopoietin 2 is a more potent predictor of diabetic nephropathy compared to neuropeptide Y.
Rickettsia parkeri and Candidatus Rickettsia andeanae in Amblyomma maculatum Group Ticks

We determined prevalence of Rickettsia spp. in 172 ticks of the Amblyomma maculatum group collected from 16 urban sites in Oklahoma City, Oklahoma, USA, during 2017 and 2018. Most ticks (59.3%) were collected from 1 site; 4 (2.3%) were infected with Rickettsia parkeri and 118 (68.6%) with Candidatus Rickettsia andeanae.
Global Expansion of Pacific Northwest Vibrio parahaemolyticus Sequence Type 36

We report transcontinental expansion of Vibrio parahaemolyticus sequence type 36 into Lima, Peru. From national collections, we identified 7 isolates from 2 different Pacific Northwest complex lineages that surfaced during 2011–2016. Sequence type 36 is likely established in environmental reservoirs. Systematic surveillance enabled detection of these epidemic isolates.
Tetraspanin 33 (TSPAN33) regulates endocytosis and migration of human B lymphocytes by affecting the tension of the plasma membrane

B lymphocytes are a leukocyte subset capable of developing several functions apart from differentiating into antibody‐secreting cells. These processes are triggered by external activation signals that induce changes in the plasma membrane properties, regulated by the formation of different lipid‐bilayer subdomains that are associated with the underlying cytoskeleton through different linker molecules, thus allowing the functional specialization of regions within the membrane. Among these, there are tetraspanin‐enriched domains. Tetraspanins constitute a superfamily of transmembrane proteins that establish lateral associations with other molecules, determining its activity and localization. In this study, we identified TSPAN33 as an active player during B‐lymphocyte cytoskeleton and plasma membrane‐related phenomena, including protrusion formation, adhesion, phagocytosis, and cell motility. By using an overexpression model of TSPAN33 in human Raji cells, we detected a specific distribution of this protein that includes membrane microvilli, the Golgi apparatus, and extracellular vesicles. Additionally, we identified diminished phagocytic ability and altered cell adhesion properties due to the aberrant expression of integrins. Accordingly, these cells presented an enhanced migratory phenotype, as shown by its augmented chemotaxis and invasion rates. When we evaluated the mechanic response of cells during fibronectin‐induced spreading, we found that TSPAN33 expression inhibited changes in roughness and membrane tension. Contrariwise, TSPAN33 knockdown cells displayed opposite phenotypes to those observed in the overexpression model. Altogether, our data indicate that TSPAN33 represents a regulatory element of the adhesion and migration of B lymphocytes, suggesting a novel implication of this tetraspanin in the control of the mechanical properties of their plasma membrane.
VYC-25L Hyaluronic Acid Injectable Gel Is Safe and Effective for Long-Term Restoration and Creation of Volume of the Lower Face

Abstract Background Juvéderm Volux (VYC-25L; Allergan plc) is an injectable hyaluronic acid gel designed to restore and create facial volume. Objective The aim of this study was to evaluate the safety and effectiveness of Volux for chin retrusion over 18 months and after repeat treatment. Methods This prospective, single-blind, controlled study enrolled subjects aged ≥18 years with chin retrusion (glabella-subnasale-pogonion facial angle 145°-165°). Subjects were randomized (3:1) to Volux at study onset or 3 months later (control group), and could receive a single repeat treatment during months 18 to 24. Assessments included mean facial-angle change from baseline, Global Aesthetic Improvement Scale (GAIS) responder rates (improved/much improved), improvements in 3 subject-reported FACE-Q scales, and safety. Results Of 132 enrolled subjects, 119 received initial Volux treatment and 89 received repeat treatment. Mean changes (95% confidence interval) in glabella-subnasale-pogonion angle from baseline for treatment and control groups, respectively, were: 1.15° (0.75°, 1.56°) and 1.16° (0.57°, 1.75°) at month 18, and 3.14° (2.68°, 3.61°) and 2.72° (1.78°, 3.66°) 1 month after repeat treatment. Investigators rated 52.5%/60.0% of treated/control subjects at month 18 and 96.9%/100% after retreatment as GAIS responders; subject-reported rates were 62.0%/64.0% and 93.8%/100%. Durable improvements in Satisfaction with Chin, Satisfaction with Lower Face and Jawline, and Psychological Well-Being were reported in 82.1%, 78.2%, and 60.3% of subjects, respectively, at month 18, and 92.3%, 93.8%, and 67.7% of subjects after retreatment. The safety profile was as expected. Conclusions Volux injectable gel is a safe, effective, and durable alternative to surgical treatments for increasing chin projection and jaw volume, and results in high patient satisfaction. Level of Evidence: 2