Miracle-dz/UniFAR-FTUs huggingface dataset:
Three-dimensional assessment of craniofacial asymmetry in children with transverse maxillary deficiency after rapid maxillary expansion: a prospective study.

OBJECTIVE The aim of this study was to evaluate craniofacial asymmetry in children with transverse maxillary deficiency, with or without functional unilateral posterior crossbite (UPC), before and after rapid maxillary expansion (RME). SETTING AND SAMPLE POPULATION A sample of 51 children with cone beam computed tomography scans obtained before RME (T1) and a year after RME (T2). MATERIAL AND METHODS This prospective study consisted of 2 groups: 25 children with functional UPC (6.77 +/- 1.5y) and 26 children without UPC (7.41 +/-1.31 y). Linear and angular measurements were obtained from zygomatic, maxilla, glenoid fossa, and mandible, using original and mirrored 3D overlapped models. All right and left side comparisons in both groups and intergroups asymmetries were compared using MANOVA and t-test for independent samples, respectively, statistically significant at p <. 05. RESULTS The UPC group showed no side differences, but mandibular horizontal rotation at T1, and this asymmetry was improved in T2. The non-UPC group showed at baseline significant lateral asymmetry in orbitale, position of palatine foramen, respectively in average 2.95 mm and 1.16 mm, and 0.49 mm of average asymmetry in condylar height. The glenoid fossa was symmetric in both groups at T1 and T2. CONCLUSIONS Children with transverse maxillary deficiency showed slight morphological asymmetry, located in the mandible position in cases of UPC, and in the orbital and maxillary regions in cases without UPC. One year after RME, patients improved their craniofacial asymmetry, with significant changes in the mandible and correction of the mandibular rotation in patients who presented UPC.
Pharmacokinetic profile of the selective 5-HT3 receptor antagonist ondansetron in the rat: an original study and a mini-review of the behavioural pharmacological literature in the rat.

Selective pharmacological modulation of the 5-hydroxytryptamine (5-HT) type 3 (5-HT3) receptor has led to the development of therapeutics including ondansetron, a highly-selective 5-HT3 antagonist used as an anti-emetic for patients undergoing chemotherapy. Pre-clinical studies in rat have shown the effects of small doses of ondansetron on cognition, behavioural sensitisation and epilepsy. However, the pharmacokinetic (PK) profile of ondansetron in rat has not been described, which limits the translational relevance of these findings. Here, we aim to determine the PK profile of ondansetron in the plasma and associated brain levels in rat. Plasma and brain levels of ondansetron were determined using high-performance liquid chromatography-tandem mass spectrometry. Following administration of ondansetron 0.1, 1 and 10 µg/kg sub-cutaneously, ondansetron plasma levels (≈ 30 - 3,000 pg/mL) were below levels achieved with doses usually administered in the clinic, with a rapid absorption phase and a short half-life (≈ 30 - 40 min). Brain levels of ondansetron were lower than plasma concentrations, with brain:plasma ratios of 0.45 and 0.46 in motor and pre-frontal cortices. We discuss our findings in the context of a mini-review of the literature. We hope that our study will be helpful to the design of pre-clinical studies with therapeutic end-points.
A Mechanistically and Operationally Simple Route to Metal-N-Heterocyclic Carbene (NHC) Complexes.

We have been puzzled by the involvement of weak organic and inorganic bases in the synthesis of metal-N-heterocyclic carbene (NHC) complexes. Such bases are insufficiently strong to permit the presumed required deprotonation of the azolium salt (the carbene precursor) prior to metal binding. Experimental and computational studies provide support for a base-assisted concerted process that does not require free NHC formation. The synthetic protocol was found applicable to a number of Transition Metal- and Main Group-centered NHC compounds and could become the synthetic route of choice to form M-NHC bonds.
The Toxoplasma gondii Cyst Wall Interactome

A model of the cyst wall interactome was constructed using proteins identified through BioID. The proteins within this cyst wall interactome model encompass several proteins identified in a prior characterization of the cyst wall proteome. This model provides a more comprehensive understanding of the composition of the cyst wall and may lead to insights on how the cyst wall is formed. ABSTRACT A characteristic of the latent cyst stage of Toxoplasma gondii is a thick cyst wall that forms underneath the membrane of the bradyzoite vacuole. Previously, our laboratory group published a proteomic analysis of purified in vitro cyst wall fragments that identified an inventory of cyst wall components. To further refine our understanding of the composition of the cyst wall, several cyst wall proteins were tagged with a promiscuous biotin ligase (BirA*), and their interacting partners were screened by streptavidin affinity purification. Within the cyst wall pulldowns, previously described cyst wall proteins, dense granule proteins, and uncharacterized hypothetical proteins were identified. Several of the newly identified hypothetical proteins were validated to be novel components of the cyst wall and tagged with BirA* to expand the model of the cyst wall interactome. Community detection of the cyst wall interactome model revealed three distinct clusters: a dense granule, a cyst matrix, and a cyst wall cluster. Characterization of several of the identified cyst wall proteins using genetic strategies revealed that MCP3 affects in vivo cyst sizes. This study provides a model of the potential protein interactions within the cyst wall and the groundwork to understand cyst wall formation. IMPORTANCE A model of the cyst wall interactome was constructed using proteins identified through BioID. The proteins within this cyst wall interactome model encompass several proteins identified in a prior characterization of the cyst wall proteome. This model provides a more comprehensive understanding of the composition of the cyst wall and may lead to insights on how the cyst wall is formed.
Potency Assessment of CBD Oils by Their Effects on Cell Signaling Pathways

This study used nanofluidic protein posttranslational modification (PTM) profiling to measure the effects of six cannabidiol (CBD) oils and isolated CBD on the signaling pathways of a cultured SH-SY5Y neuronal cell line. Chemical composition analysis revealed that all CBD oils met the label claims and legal regulatory limit regarding the CBD and tetrahydrocannabinol (THC) contents, respectively. Isolated CBD was cytotoxic, with an effective concentration (EC50) of 40 µM. In contrast, the CBD oils had no effect on cell viability at CBD concentrations exceeding 1.2 mM. Interestingly, only an unadulterated CBD oil had strong and statistically significant suppressive effects on the pI3K/Akt/mTOR signaling pathway with an EC50 value of 143 µM and a slow-acting timescale requiring hours. Systematic profiling of twenty-six proteins, which served as biomarkers for nine signaling pathways, revealed that the unadulterated CBD oil downregulated seven signaling pathways but had no measurable effect on the other two signaling pathways. The remaining CBD oils, which were adulterated, and isolated CBD had weak, variable, or undetectable effects on neuronal signaling pathways. Our data clearly showed that adulteration diminished the biological activities of CBD oils. In addition, nanofluidic protein PTM profiling provided a robust means for potency assessment of CBD oils.
Impact of CT Injector Technology and Contrast Media Viscosity on Vascular Enhancement: Evaluation in a Circulation Phantom

Objective: To assess the impact of piston-based vs peristaltic injection system technology and contrast media viscosity on achievable iodine delivery rates (IDRs) and vascular enhancement in a pre-clinical study. Methods: Four injectors were tested: MEDRAD® Centargo, MEDRAD® Stellant, CT Exprès®, and CT motion™ using five contrast media [iopromide (300 and 370 mgI ml−1), iodixanol 320 mgI ml−1, iohexol 350 mgI ml−1, iomeprol 400 mgI ml−1]. Three experiments were performed evaluating achievable IDR and corresponding enhancement in a circulation phantom. Results: Experiment I: Centargo provided the highest achievable IDRs with all tested contrast media (p < 0.05). Iopromide 370 yielded the highest IDR with an 18G catheter (3.15 gI/s); iopromide 300 yielded the highest IDR with 20G (2.70 gI/s) and 22G (1.65 gI/s) catheters (p < 0.05). Experiment II: with higher achievable IDRs, piston-based injectors provided significantly higher peak vascular enhancement (up to 48% increase) than the peristaltic injectors with programmed IDRs from 1.8 to 2.4 gI/s (p < 0.05). Experiment III: with programmed IDRs (e.g. 1.5 gI/s) achievable by all injection systems, Centargo, with sharper measured bolus shape, provided significant increases in enhancement of 34–73 HU in the pulmonary artery with iopromide 370 (p < 0.05). Conclusion: The tested piston-based injection systems combined with low viscosity contrast media provide higher achievable IDRs and higher peak vascular enhancement than the tested peristaltic-based injectors. With equivalent IDRs, Centargo provides higher peak vascular enhancement due to improved bolus shape. Advances in knowledge: This paper introduces a new parameter to compare expected performance among contrast media: the concentration/viscosity ratio. Additionally, it demonstrates previously unexplored impacts of bolus shape on vascular enhancement.
Congenital heart defects in Noonan syndrome: Diagnosis, management, and treatment

Noonan syndrome is a pleomorphic genetic disorder, in which a high percentage of affected individuals have cardiovascular involvement, most prevalently various forms of congenital heart disease (i.e., pulmonary valve stenosis, septal defects, left‐sided lesions, and complex forms with multiple anomalies). Care includes attentiveness to several comorbidities, some directly impacting cardiac management (bleeding diatheses and lymphatic anomalies). More than 50% of patients with Noonan syndrome harbor PTPN11 pathogenic variation, which results in hyperactivation of RAS/mitogen‐activated protein kinase signaling. Several other disease genes with similar biological effects have been uncovered for NS and phenotypically related disorders, collectively called the RASopathies. Molecular diagnosis with gene resequencing panels is now widely available, but phenotype variability and in some cases, subtlety, continues to make identification of Noonan syndrome difficult. Until genetic testing becomes universal for patients with congenital heart disease, alertness to Noonan syndrome's broad clinical presentations remains crucial. Genotype–phenotype associations for Noonan syndrome enable better prognostication for affected patients when a molecular diagnosis is established. We still lack Noonan syndrome‐specific treatment; however, newly developed anticancer RAS pathway inhibitors could fill that gap if safety and efficacy can be established for indications such as pulmonary valve stenosis.
The nexus between corporate governance, risk taking, and growth

In this study we assess the impact of corporate governance on the risk investment behavior of firms and its implications on firms’ growth rate. Using a sample of non-financial companies from 10 countries over a period leading to the recent global financial crisis, we documented that the corporate governance has a nonlinear (inverted U-shape) impact on the companies’ investment risk, meaning that the investment risk is increasing up to a level of corporate governance of 0.61 (as measured by our comprehensive index), while at higher levels of corporate governance the investment risk is decreasing. For the models of sales growth and assets growth it is shown that predicted investment risk has a positive effect on firms’ growth measures. Moreover, the two growth models are not moving independently and a shock to one of the growth measures (sales or assets) affects the other growth measure in the same direction. Additionally, we evaluated the effect of financial crisis on both the growth measures and the risk measure. The effect of financial crisis was captured in both measures in 2009, with higher impact on the growth of sales.
Angiographic biomarkers of filtering bleb function after XEN gel implantation for glaucoma: an optical coherence tomography-angiography study.

PURPOSE To evaluate, using optical coherence tomography-angiography (OCT-A), the vascular features of good bleb function after XEN gel implantation (XGI) for uncontrolled glaucoma. METHODS Forty-three patients (43 eyes), who underwent XGI, were enrolled. According to the intraocular pressure (IOP) reduction, patients were classified into Group 1 (21 eyes; success) and Group 2 (22 eyes; failure). Optical coherence tomography-angiography (OCT-A) was performed to image the vascularization of the conjunctival bleb-wall. The main outcomes were as follows: vessel displacement areas (VDAs), major vessel displacement area (MVDA; mm2 ), non-flow whole area (NFWA; mm2 ) and bleb-wall vessel density (BVD; %). Co-registered B-scans were also considered to evaluate the bleb-wall cyst-like structure density and area (BCSD, cysts/mm2 ; BCSA, mm2 ), and the bleb-wall thickness (BT, µm). RESULTS Mean postoperative follow-up was 7.5 ± 0.14 months; Group 1 and 2 IOP were 14.0 ± 2.5 and 25.3 ± 2.1 mmHg, respectively (p < 0.001). Greater VDA (p < 0.001), MVDA (p = 0.046) and NFWA (p = 0.001) values, and lower BVD (p < 0.001) was found in Group 1 compared to Group 2. Group 1 showed higher BSCD, BSCA and BT values compared to Group 2 (p < 0.001). Postoperative IOP positively correlated with BVD (r = 0.567; p = 0.003), but negatively with VDAs, MVDA (r = -0.581, p = 0.002; r = -0.619, p = 0.001, respectively), BCSD, BCSA (r = -0.580; p = 0.002; r = -0.664; p < 0.001) and BT (r = -0.627, p = 0.001). CONCLUSION Successful filtration blebs after XGI present numerous and large areas of vessel displacement within the bleb-wall, along with a rarefied vascular network. These OCT-A features can be considered angiographic biomarkers of a good aqueous humour percolation through the bleb-wall layers.
Biotechnology and Bioengineering

Correspondence João R. C. Ramos, Bioprocess Engineering, Max Planck Institute for Dynamics of Complex Technical Systems, Bioprocess Engineering, Sandtorstr 1, 39106 Magdeburg, Germany. Email: rodrigues_correira_r@mpi-magdeburg. mpg.de Abstract Mathematical modeling of animal cell growth and metabolism is essential for the understanding and improvement of the production of biopharmaceuticals. Models can explain the dynamic behavior of cell growth and product formation, support the identification of the most relevant parameters for process design, and significantly reduce the number of experiments to be performed for process optimization. Few dynamic models have been established that describe both extracellular and intracellular dynamics of growth and metabolism of animal cells. In this study, a model was developed, which comprises a set of 33 ordinary differential equations to describe batch cultivations of suspension AGE1.HN. AAT cells considered for the production of α1‐antitrypsin. This model combines a segregated cell growth model with a structured model of intracellular metabolism. Overall, it considers the viable cell concentration, mean cell diameter, viable cell volume, concentration of extracellular substrates, and intracellular concentrations of key metabolites from the central carbon metabolism. Furthermore, the release of metabolic by‐products such as lactate and ammonium was estimated directly from the intracellular reactions. Based on the same set of parameters, this model simulates well the dynamics of four independent batch cultivations. Analysis of the simulated intracellular rates revealed at least two distinct cellular physiological states. The first physiological state was characterized by a high glycolytic rate and high lactate production. Whereas the second state was characterized by efficient adenosine triphosphate production, a low glycolytic rate, and reactions of the TCA cycle running in the reverse direction from α‐ketoglutarate to citrate. Finally, we show possible applications of the model for cell line engineering and media optimization with two case studies.
Multidrug-resistant strains of coagulase-negative staphylococci isolated from patients with chronic sinusitis - MDR, XDR, PDR strains.

INTRODUCTION The development of resistance to multiple antimicrobial agents in pathogenic bacteria has become a threat to public health. Multidrug-resistant strains that are particularly dangerous include MDR, XDR and PDR strains. MATERIAL AND METHODS Aspirate material from paranasal sinuses, obtained from patients with chronic sinusitis undergoing functional endoscopic sinus surgery (FESS) in Medical Center MML in Warsaw, was subjected to bacteriologic analysis. The isolated strains were identified to the species level and tested for antibiotic resistance. Then, minimal inhibitory concentration (MIC) was determined. R esults: The isolated strains of coagulase-negative staphylococci were resistant mainly to macrolides, aminoglycosides and tetracycline. Nine of the isolated strains exhibited multidrug-resistance. DISCUSSION Bacteria causing chronic sinusitis are becoming increasingly resistant to antimicrobial agents. The diagnostic process for coagulase-negative staphylococci (CNS) is often limited to the identification of species, or even genus of the bacteria. The CNS strains are considered to be non-pathogenic and they are not subject to eradication. This may lead to erroneous therapeutic decisions and, consequently, to the development of antibiotic resistance. CNS infections are classified as nosocomial and therefore, appropriate epidemiological procedures have to be followed. The authors highlight the necessity to determine MIC values for antibiotics and to introduce personalized treatment.
A 3‐year prospective study of a multidisciplinary early proactive therapeutic drug monitoring programme of infliximab treatments in inflammatory bowel disease

Therapeutic drug monitoring (TDM) of trough serum infliximab concentrations has been mainly used in case of loss of response in patients with inflammatory bowel disease (IBD). The aim of this study was to evaluate the effectiveness and safety of a multidisciplinary early proactive TDM (mep‐TDM) programme for dose adjustment.
Velocity-based resistance training: Impact of velocity loss in the set on neuromuscular performance and hormonal response.

This study aimed to compare the effects of two resistance training (RT) programs with different velocity losses allowed in each set: 10% (VL10%) vs. 30% (VL30%) on neuromuscular performance and hormonal response. Twenty-five young healthy males were randomly assigned into two groups: VL10% (n=12) or VL30% (n=13). Subjects followed a velocity-based RT program for 8 weeks (2 sessions per week) using only the full-squat (SQ) exercise at 70-85% 1RM. Repetition velocity was recorded in all training sessions. A 20-m running sprint, countermovement jump (CMJ), 1RM, muscle endurance and EMG during SQ exercise, and resting hormonal concentrations were assessed before and after RT program. Both groups showed similar improvements in muscle strength and endurance variables (VL10%: 7.0-74.8%; VL30%: 4.2-73.2%). The VL10% resulted in greater percentage increments in CMJ (9.2% vs. 5.4%) and sprint performance (-1.5% vs. 0.4%) than VL30%, despite VL10% performed less than half of the repetitions than VL30% during RT. In addition, only VL10% showed slight increments in EMG variables, whereas no significant changes in resting hormonal concentrations were observed. Therefore, our results suggest that velocity losses in the set as low as 10% are enough to achieve significant improvements in neuromuscular performance, which means greater efficiency during RT. Novelty bullets • The VL10% group showed similar or even greater percentage of changes in physical performance compared to VL30%. • No significant changes in resting hormonal concentrations were observed for any training group. • Curvilinear relationships between percentage VL in the set and changes in strength and CMJ performance were observed.
Oral Nutritional Supplementation Following Upper Gastrointestinal Cancer Surgery: A Prospective Analysis Exploring Potential Barriers to Compliance

Abstract Objective: Malnutrition is common in patients who underwent upper gastrointestinal cancer surgery. Our goal was to explore postoperative compliance with oral nutritional supplementation and define barriers to consumption in patients with esophageal, gastroesophageal junction, and gastric cancer. Methods: Participants were prospectively recruited from September 2015 to November 2018. Preoperative nutritional status was assessed using the Patient Generated Subjective Global Assessment. Malnourished patients and patients at risk for malnutrition were offered oral nutritional supplementation at the time of hospital discharge. Compliance was evaluated 1 month after hospital discharge. Results: A total of 78 patients were analyzed. Mean patient age was 62.8 ± 10.7 years and 83.3% were males. Εsophagectomy and gastrectomy were performed in 60.3% and 39.7% of the patients respectively. Twenty-eight (35.9%) participants reported consuming all prescribed supplements, whereas 50 (64.1%) patients were noncompliant with their prescribed oral nutritional supplementation regimen. The main barriers to oral nutritional supplementation compliance were bloating (compliant vs. noncompliant patients: 17.9% vs. 58%, p < 0.001), early satiety (compliant vs. noncompliant patients: 25% vs. 52.32%, p < 0.001), flavor or texture dislike (compliant vs. noncompliant patients: 7.1% vs. 34%, p < 0.001), and diarrhea (compliant vs. noncompliant patients: 10.7% vs. 24%, p < 0.001). No other statistically significant differences were identified between the two groups. Conclusions: Postoperative compliance to oral nutritional supplementation is low in patients who underwent upper gastrointestinal cancer surgery. Patient education and support as well as providing a range of oral nutrition supplement flavors, texture, and compositions may be useful in increasing adherence to oral nutritional supplementation regimens.
Synaptic Integration of Thalamic and Limbic Inputs in Rodent Gustatory Cortex

Abstract Neurons in the gustatory cortex (GC) process multiple aspects of a tasting experience, encoding not only the physiochemical identity of tastes, but also their anticipation and hedonic value. Information pertaining to these stimulus features is relayed to GC via the gustatory thalamus (VPMpc) and basolateral amygdala (BLA). It is not known whether these inputs drive separate groups of neurons, thus activating separate channels of information, or are integrated by neurons that receive both afferents. Here, we used anterograde labeling and in vivo intracellular recordings in anesthetized rats to assess the potential convergence of BLA and VPMpc inputs in GC, and to investigate the dynamics of integration of these inputs. We report substantial anatomic overlap of BLA and VPMpc axonal fields across GC, and identify a population of GC neurons receiving converging BLA and VPMpc inputs. Our data show that BLA modulates the gain of VPMpc-evoked responses in a time-dependent fashion and that this modulation is dependent on the recruitment of synaptic inhibition by both BLA and VPMpc. Our results suggest that BLA shapes cortical processing of thalamic inputs by dynamically gating the excitatory/inhibitory balance of the GC circuit.