Miracle-dz/UniFAR-FTUs huggingface dataset:
Progression in the Management of Non-Idiopathic Pulmonary Fibrosis Interstitial Lung Diseases, Where Are We Now and Where We Would Like to Be

A significant proportion of patients with interstitial lung disease (ILD) may develop a progressive fibrosing phenotype characterized by worsening of symptoms and pulmonary function, progressive fibrosis on chest computed tomography and increased mortality. The clinical course in these patients mimics the relentless progressiveness of idiopathic pulmonary fibrosis (IPF). Common pathophysiological mechanisms such as a shared genetic susceptibility and a common downstream pathway—self-sustaining fibroproliferation—support the concept of a progressive fibrosing phenotype, which is applicable to a broad range of non-IPF ILDs. While antifibrotic drugs became the standard of care in IPF, immunosuppressive agents are still the mainstay of treatment in non-IPF fibrosing ILD (F-ILD). However, recently, randomized placebo-controlled trials have demonstrated the efficacy and safety of antifibrotic treatment in systemic sclerosis-associated F-ILD and a broad range of F-ILDs with a progressive phenotype. This review summarizes the current pharmacological management and highlights the unmet needs in patients with non-IPF ILD.
Assessing the Association Between Nutritional Status, Caries, and Gingivitis in Schoolchildren: A Cross-Sectional Study

Objective. To evaluate if nutritional status is associated with caries and gingivitis in Brazilian schoolchildren. Material and methods. Children of both genders, age ranging from 8 to 11 years old, were included in this study. Caries was diagnosed using ICDAS (International System for Detection and Assessment of Carious Lesions) and gingivitis was diagnosed using the Community Periodontal Index. The nutritional status of each child was defined by BMI Z-score calculation. Data on oral health behavior and dietary habit were collected through parent’s questionnaires. Parametric analyzes were performed to compare the groups. The established alpha was 5%. Results. The sample consisted of 353 schoolchildren: 16 underweight children, 247 eutrophic children, 64 overweight children, and 26 were obese children. Overweight, Obese and Overweight + Obese children presented less cavitated caries lesion than Eutrophic children (P < .05). Gingivitis was not associated with nutritional status (P > .05). Conclusion. Caries was associated with overweight and obesity in Brazilian schoolchildren.
Nonhydrolytic Sol−Gel Routes to Oxides

This review surveys the chemistry of various nonhydrolytic sol−gel processes including hydroxylation in nonaqueous systems and aprotic condensation reactions. Some examples of applications in the field of single and multicomponent oxides demonstrate the interest of these approaches as alternatives to the usual hydrolytic routes. More particularly nonhydrolytic methods lead to improved control over the molecular level homogeneity and stoichiometry of multicomponent oxides.
Surface Modifications of Titanium Aluminium Vanadium Improve Biocompatibility and Osteogenic Differentiation Potential

Osteogenic cells are strongly influenced in their behaviour by the surface properties of orthopaedic implant materials. Mesenchymal stem and progenitor cells (MSPCs) migrate to the bone–implant interface, adhere to the material surface, proliferate and subsequently differentiate into osteoblasts, which are responsible for the formation of the bone matrix. Five surface topographies on titanium aluminium vanadium (TiAl6V4) were engineered to investigate biocompatibility and adhesion potential of human osteoblasts and the changes in osteogenic differentiation of MSPCs. Elemental analysis of TiAl6V4 discs coated with titanium nitride (TiN), silver (Ag), roughened surface, and pure titanium (cpTi) surface was analysed using energy-dispersive X-ray spectroscopy and scanning electron microscopy. In vitro cell viability, cytotoxicity, adhesion behaviour, and osteogenic differentiation potential were measured via CellTiter-Glo, CytoTox, ELISA, Luminex® technology, and RT-PCR respectively. The Ag coating reduced the growth of osteoblasts, whereas the viability of MSPCs increased significantly. The roughened and the cpTi surface improved the viability of all cell types. The additive coatings of the TiAl6V4 alloy improved the adhesion of osteoblasts and MSPCs. With regard to the osteogenic differentiation potential, an enhanced effect has been demonstrated, especially in the case of roughened and cpTi coatings.
Weekly Internal Ethical Case Discussions in an ICU—Results Based on 9 Years of Experience With a Highly Structured Approach

Supplemental Digital Content is available in the text. Objectives: Various ethical challenges are prevalent in ICUs. In order to handle these problems, a highly structured internal ethical case discussion within the multiprofessional team was implemented in 2011 in a Swiss ICU and has been regularly practiced almost weekly until present. To explore the results of all ethical case discussions taking place in a general ICU and to discuss the outcomes of the patients. To identify the conditions facilitating the implementation of regular ethical case discussions. Design: Retrospective case series analysis. Setting: Mixed academic ICU. Patients AND INTERVENTION: All patients who had an ethical case discussion between January 2011 and December 2019 following the approach called Modular, Ethical, Treatment decisions, Allocation of resources at the micro-level, and Process. MEASUREMENTS AND Main Results: Weekly ethical case discussions held regularly on a fixed date were found to be practical for the observed ICU. A total of 314 ethical case discussions were realized in 281 patients. Median patient age was 70 years (interquartile range, 62–77 yr); two thirds were men. The results were categorized into the following groups: established therapy continues, complications to be treated (n = 53; 16.9%); therapy continues, patient’s will to be explored further (n = 77; 24.5%); therapy continues, complications to be treated only after evaluation (n = 62; 19.7%); therapy continues with limitations (e.g., do-not-resuscitate order) (n = 98; 31.2%); and change of treatment plan to end-of-life care (n = 17; 5.4%). Of the discussed patients, 115 (40.9%) died in the ICU and 29 (10.3%) after transfer to the normal ward. Seven patients (2.5%) were transferred to a hospice and 55 (19.6%) to another hospital. Sixty-nine (24.6%) were discharged to a rehabilitative facility and six returned home. Conclusions: Regular ethical case discussions can be successfully implemented, enabling careful review of the patient’s will and balancing it with the prognosis of the disease. This facilitates a necessary change of the therapeutic goal whenever appropriate.
UV Nanoimprint Lithography: Geometrical Impact on Filling Properties of Nanoscale Patterns

Ultraviolet (UV) Nanoimprint Lithography (NIL) is a replication method that is well known for its capability to address a wide range of pattern sizes and shapes. It has proven to be an efficient production method for patterning resist layers with features ranging from a few hundred micrometers and down to the nanometer range. Best results can be achieved if the fundamental behavior of the imprint resist and the pattern filling are considered by the equipment and process parameters. In particular, the material properties and pattern size and shape play a crucial role. For capillary force-driven filling behavior it is important to understand the influencing parameters and respective failure modes in order to optimize the processes for reliable full wafer manufacturing. In this work, the nanoimprint results obtained for different pattern geometries are compared with respect to pattern quality and residual layer thickness: The comprehensive overview of the relevant process parameters is helpful for setting up NIL processes for different nanostructures with minimum layer thickness.
The Association between Quitline Characteristics and Smoking Cessation by Educational Attainment, Income, Race/Ethnicity, and Sex

Little research examines how tobacco quitlines affect disparities in smoking cessation in the United States. Our study utilized data from the Tobacco Use Supplement to the Current Population Survey (2010, 2011, 2012, 2015, 2018) (TUS-CPS) and state-level quitline data from the North American Quitline Consortium and National Quitline Data Warehouse. We ran multilevel logistic regression models assessing a state-run quitline’s budget, reach, number of counseling sessions offered per caller, and hours of operation on 90-day smoking cessation. Multiplicative interactions between all exposures and sex, race/ethnicity, income, and education were tested to understand potential effect modification. We found no evidence that budget, reach, number of counseling sessions, or hours available for counseling were associated with cessation in the main effects analyses. However, when looking at effect modification by sex, we found that higher budgets were associated with greater cessation in males relative to females. Further, higher budgets and offering more sessions had a stronger association with cessation among individuals with lower education, while available counseling hours were more strongly associated with cessation among those with higher education. No quitline characteristics examined were associated with smoking cessation. We found evidence for effect modification by sex and education. Despite proven efficacy at the individual-level, current resource allocation to quitlines may not be sufficient to improve rates of cessation.
Performance Evaluation of a Novel Biosourced Co-Processed Excipient in Direct Compression and Drug Release

This study exposes the potential usefulness of a new co-processed excipient, composed of alginic acid and microcrystalline cellulose (Cop AA-MCC), for the preparation of immediate drug release tablets by direct compression. Evaluation of the physical and mechanical properties as well as the disintegration behavior of Cop AA-MCC in comparison to commercial co-processed excipients (Cellactose®, Ludipress®, Prosolv® SMCC HD90 and Prosolv® ODT) and to the physical mixture of the native excipients (MCC and AA), was carried out. The obtained results illustrate the good performance of Cop AA-MCC in terms of powder flowability, tablet tensile strength, compressibility, and disintegration time. Although, this new co-processed excipient showed a slightly high lubricant sensitivity, which was explained by its more plastic than fragmentary deformation behavior, it presented a low lubricant requirement due to the remarkably low ejection force observed during compression. Compression speed and dwell time seemed not to affect significantly the tabletability of Cop AA-MCC. The study exposed evenly the performance of Cop AA-MCC compared to Prosolv® ODT, in terms of tabletability and dissolution rate of Melatonin. Cop AA-MCC presented comparable hardness, lower dilution potential, higher lubricant sensitivity, lower ejection force, and faster Melatonin’s release time than Prosolv® ODT. In summary, Cop AA-MCC exhibited interesting physical, mechanical, and biopharmaceutical properties, which demonstrate its concurrence to commercially available co-processed excipients. Furthermore, the simplicity of its composition and the scalability of its elaboration makes this multifunctional excipient highly recommended for direct compression.
Radiological Surveillance Post-Curative Colorectal Cancer Resection: Is There a Need for a Targeted Protocol?

Background The frequency of radiological surveillance after curative colorectal cancer resection has long been a controversial issue with the need to balance potential harm from ionizing radiation and the financial burden of intense surveillance against advantages of early detection of recurrent disease. NICE guidelines issued in 2018 suggested having two surveillance computed tomography (CT) scans within three years of surgery without specifying the timing or the interval. Aim To examine whether an evidence-based flexible approach based on individual patients’ risk factors can add value to surveillance protocols. Reaching a targeted protocol that can maximize early detection of metastasis without consumption of resources and most important without compromising patient safety. Methodology A retrospective study involving five years of data of patients who underwent curative colorectal cancer resections. Data extracted after patients completed their three-year surveillance CT scans, CT reports retrieved together with post-operative histology reports, and a detailed database was constructed. Results Of 179 patients included, 66 developed recurrence (7 local and 59 distant). Recurrence increased from 23.5% in T1 to 66% in T4 (P=0.0001). The median time to recurrence 23 months in T4 disease compared to 36, 42 and 43 months for stages T1, T2 and T3, respectively (P=0.0001). A similar incremental increase in recurrence noted from 22% in the N0 stage to 73.5% in the N2 stage (P=0.0001); the median time to recurrence of 14 months in N2 patients compared to 45 and 33 months for stages N0 and N1, respectively (P=0.0001). Recurrence correlated well with positive extramural vascular invasion (EMVI) status, (71.7% versus 19.3% P=0.0001) being detected significantly earlier in EMVI positive group at 17 versus 45 months (P=0.0001). Conclusion Flexible protocol for radiological surveillance after curative resection of colorectal cancer, based on known pathological prognostic factors, is likely to be more effective in maximizing resource utilization as well as improving patient outcomes.
Proteomic Approaches to Dissect Host SUMOylation during Innate Antiviral Immune Responses

SUMOylation is a highly dynamic ubiquitin-like post-translational modification that is essential for cells to respond to and resolve various genotoxic and proteotoxic stresses. Virus infections also constitute a considerable stress scenario for cells, and recent research has started to uncover the diverse roles of SUMOylation in regulating virus replication, not least by impacting antiviral defenses. Here, we review some of the key findings of this virus-host interplay, and discuss the increasingly important contribution that large-scale, unbiased, proteomic methodologies are making to discoveries in this field. We highlight the latest proteomic technologies that have been specifically developed to understand SUMOylation dynamics in response to cellular stresses, and comment on how these techniques might be best applied to dissect the biology of SUMOylation during innate immunity. Furthermore, we showcase a selection of studies that have already used SUMO proteomics to reveal novel aspects of host innate defense against viruses, such as functional cross-talk between SUMO proteins and other ubiquitin-like modifiers, viral antagonism of SUMO-modified antiviral restriction factors, and an infection-triggered SUMO-switch that releases endogenous retroelement RNAs to stimulate antiviral interferon responses. Future research in this area has the potential to provide new and diverse mechanistic insights into host immune defenses.
Transient Receptor Potential (TRP) Channels in the Pacific Oyster (Crassostrea gigas): Genome-Wide Identification and Expression Profiling after Heat Stress between C. gigas and C. angulata

Transmembrane proteins are involved in an array of stress responses, particularly in thermo-sensation and thermo-regulation. In this study, we performed a genome-wide identification and characterization of the Transient Receptor Potential (TRP) genes in the Pacific oyster (Crassostrea gigas) and investigated their expression profiles after heat stress to identify critical TRPs potentially associated with thermal regulation. A total of 66 TRP genes were identified in the C. gigas, which showed significant gene expansion and tandem duplication. Meta-analysis of the available RNA-Seq data generated from samples after acute heat stress revealed a set of heat-inducible TRPs. Further examination of their expression profiles under chronic heat stress, and comparison between C. gigas and C. angulata, two oyster species with different tolerance levels to heat stress, led to the identification of TRPC3.6, TRPC3.7, and TRPV4.7 as important TRPs involved in thermal regulation in oysters. This work provided valuable information for future studies on the molecular mechanism of TRP mediated thermal tolerance, and identification of diagnostic biomarker for thermal stress in the oysters.
Hair Growth Promoting Activity of Cedrol Nanoemulsion in C57BL/6 Mice and Its Bioavailability

As the main component of Platycladus orientalis, cedrol has known germinal activity. A range of cedrol formulations have been developed to prevent hair-loss, but compliance remains key issues. In this study, we prepared cedrol nanoemulsion (CE-NE) and determined the particle size and PDI (polydispersion coefficient), investigated the hair growth activity and studied the bioavailability in vitro and in vivo. Results showed that the average particle size of CE-NE is 14.26 ± 0.16 nm, and the PDI value is 0.086 ± 0.019. In vitro drug release investigation and drug release kinetics analysis showed release profile of CE from nanoparticles demonstrates the preferred partition of CE in buffer pH 4.0, the release profile of CE-NE showed a first-order kinetics reaching around 36.7% after 6 h at 37 °C. We artificially depilated the back hair of C57BL/6 mice and compared the efficacy of a designed cedrol nanoemulsion to an existing ointment group. The hair follicles were imaged and quantified using a digital photomicrograph. The results showed that compared with the ointment, CE-NE had positive effects on hair growth, improved drug solubility. Compared with the ointment and 2% minoxidil groups, 50 mg/mL CE-NE led to more robust hair growth. Pharmacokinetics analysis showed that the AUC0–t of CE-NE was 4-fold higher than that of the ointment group, confirming that the bioavailability of the nanoemulsion was greater than that of the ointment. CE-NE also significantly reduced the hair growth time of model mice and significantly increased the growth rate of hair follicles. In conclusion, these data suggest that the nanoemulsion significantly improved the pharmacokinetic properties and hair growth effects cedrol, enhancing its efficacy in vitro and in vivo.
Multifunctional Tyrosinase Inhibitor Peptides with Copper Chelating, UV-Absorption and Antioxidant Activities: Kinetic and Docking Studies

Nature-derived tyrosinase inhibitors are of great industrial interest. Three monophenolase inhibitor peptides (MIPs) and three diphenolase inhibitor peptides (DIPs) from a previous study were investigated for their in vitro tyrosinase inhibitory effects, mode of inhibition, copper-chelating activity, sun protection factor (SPF) and antioxidant activities. DIP1 was found to be the most potent tyrosinase inhibitor (IC50 = 3.04 ± 0.39 mM), which could be due to the binding interactions between its aromatic amino acid residues (Y2 and D7) with tyrosinase hotspots (H85, V248, H258, H263, F264, R268, V283 and E322) and its ability to chelate copper ion within the substrate-binding pocket. The conjugated planar rings of tyrosine and tryptophan may interact with histidine within the active site to provide stability upon enzyme-peptide binding. This postulation was later confirmed as the Lineweaver–Burk analysis had identified DIP1 as a competitive inhibitor and DIP1 also showed 36.27 ± 1.17% of copper chelating activity. In addition, DIP1 provided the highest SPF value (11.9 ± 0.04) as well as ferric reducing antioxidant power (FRAP) (5.09 ± 0.13 mM FeSO4), 2,2′–azinobis(3-ethylbenzothiazoline-6-sulphonic acid) diammonium salt (ABTS) (11.34 ± 0.90%) and 2,2-diphenyl-1-picrylhydrazyl (DPPH) (29.14 ± 1.36%) free radical scavenging activities compared to other peptides. These results demonstrated that DIP1 could be a multifunctional anti-tyrosinase agent with pharmaceutical and cosmeceutical applications.
Shading Effects on Leaf Gas Exchange, Leaf Pigments and Secondary Metabolites of Polygonum minus Huds., an Aromatic Medicinal Herb

The growing demand for high value aromatic herb Polygonum minus-based products have increased in recent years, for its antioxidant, anticancer, antimicrobial, and anti-inflammatory potentials. Although few reports have indicated the chemical profiles and antioxidative effects of Polygonum minus, no study has been conducted to assess the benefits of micro-environmental manipulation (different shading levels) on the growth, leaf gas exchange and secondary metabolites in Polygonum minus. Therefore, two shading levels (50%:T2 and 70%:T3) and one absolute control (0%:T1) were studied under eight weeks and 16 weeks of exposures on Polygonum minus after two weeks. It was found that P. minus under T2 obtained the highest photosynthesis rate (14.892 µmol CO2 m−2 s−1), followed by T3 = T1. The increase in photosynthesis rate was contributed by the enhancement of the leaf pigments content (chlorophyll a and chlorophyll b). This was shown by the positive significant correlations observed between photosynthesis rate with chlorophyll a (r2 = 0.536; p ≤ 0.05) and chlorophyll b (r2 = 0.540; p ≤ 0.05). As the shading levels and time interval increased, the production of total anthocyanin content (TAC) and antioxidant properties of Ferric Reducing Antioxidant Power (FRAP) and 2,2-Diphenyl-1-picrylhydrazyl (DPPH) also increased. The total phenolic content (TPC) and total flavonoid content (TFC) were also significantly enhanced under T2 and T3. The current study suggested that P.minus induce the production of more leaf pigments and secondary metabolites as their special adaptation mechanism under low light condition. Although the biomass was affected under low light, the purpose of conducting the study to boost the bioactive properties in Polygonum minus has been fulfilled by 50% shading under 16 weeks’ exposure.
Characterization of NADPH Oxidase Expression and Activity in Acute Myeloid Leukemia Cell Lines: A Correlation with the Differentiation Status

In acute myeloid leukemia (AML), a low level of reactive oxygen species (ROS) is associated with leukemic stem cell (LSC) quiescence, whereas a high level promotes blast proliferation. ROS homeostasis relies on a tightly-regulated balance between the antioxidant and oxidant systems. Among the oxidants, NADPH oxidases (NOX) generate ROS as a physiological function. Although it has been reported in AML initiation and development, the contribution of NOX to the ROS production in AML remains to be clarified. The aim of this study was to investigate the NOX expression and function in AML, and to examine the role of NOX in blast proliferation and differentiation. First, we interrogated the NOX expression in primary cells from public datasets, and investigated their association with prognostic markers. Next, we explored the NOX expression and activity in AML cell lines, and studied the impact of NOX knockdown on cell proliferation and differentiation. We found that NOX2 is ubiquitously expressed in AML blasts, and particularly in cells from the myelomonocytic (M4) and monocytic (M5) stages; however, it is less expressed in LSCs and in relapsed AML. This is consistent with an increased expression throughout normal hematopoietic differentiation, and is reflected in AML cell lines. Nevertheless, no endogenous NOX activity could be detected in the absence of PMA stimulation. Furthermore, CYBB knockdown, although hampering induced NOX2 activity, did not affect the proliferation and differentiation of THP-1 and HL-60 cells. In summary, our data suggest that NOX2 is a marker of AML blast differentiation, while AML cell lines lack any NOX2 endogenous activity.