Miracle-dz/UniFAR-FTUs huggingface dataset:
Photoacoustic and Magnetic Resonance Imaging of Hybrid Manganese Dioxide-Coated Ultra-Small NaGdF4 Nanoparticles for Spatiotemporal Modulation of Hypoxia in Head and Neck Cancer

Simple Summary Tumor hypoxia is a documented negative prognostic factor that contributes to treatment resistance in head and neck cancer. In the present study, we use non-invasive magnetic resonance imaging (MRI) and photoacoustic imaging (PAI) to evaluate the ability of ultra-small manganese dioxide coated nanoparticles to modulate tumor oxygenation in vitro and in vivo. Our results highlight the utility of MRI and PAI in mapping tumor hypoxia and nanoparticle delivery and demonstrate the potential of image-guided nanodelivery in alleviating tumor hypoxia in head and neck cancer. Abstract There is widespread interest in developing agents to modify tumor hypoxia in head and neck squamous cell carcinomas (HNSCC). Here, we report on the synthesis, characterization, and potential utility of ultra-small NaYF4:Nd3+/NaGdF4 nanocrystals coated with manganese dioxide (usNP-MnO2) for spatiotemporal modulation of hypoxia in HNSCC. Using a dual modality imaging approach, we first visualized the release of Mn2+ using T1-weighted magnetic resonance imaging (MRI) and modulation of oxygen saturation (%sO2) using photoacoustic imaging (PAI) in vascular channel phantoms. Combined MRI and PAI performed in patient-derived HNSCC xenografts following local and systemic delivery of the hybrid nanoparticles enabled mapping of intratumoral nanoparticle accumulation (based on T1 contrast enhancement) and improvement in tumor oxygenation (increased %sO2) within the tumor microenvironment. Our results demonstrate the potential of hybrid nanoparticles for the modulation of tumor hypoxia in head and neck cancer. Our findings also highlight the potential of combined MRI-PAI for simultaneous mapping nanoparticle delivery and oxygenation changes in tumors. Such imaging methods could be valuable in the precise selection of patients that are likely to benefit from hypoxia-modifying nanotherapies.
Responsibilities and capabilities of health engagement professionals (HEPs): Perspectives from HEPs and health consumers in Australia

In Australia, the National Safety and Quality Health Service Standards (2012) stipulates that partnering with health consumers to improve health‐care experiences is one of the criteria health‐care organizations are assessed and accredited against. This standard has given rise to a role: health engagement professionals (HEPs). While there are no standard requirements for recruitment into this role, this study contributes to much needed research into understanding their responsibilities and capabilities, and their contributions to engagement outcomes.
Clinical Experience With Severe Acute Respiratory Syndrome Coronavirus 2–Related Illness in Children: Hospital Experience in Cape Town, South Africa

Abstract Background Children seem relatively protected from serious severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)–related disease, but little is known about children living in settings with high tuberculosis and human immunodeficiency virus (HIV) burden. This study reflects clinical data on South African children with SARS-CoV-2. Methods We collected clinical data of children aged <13 years with laboratory-confirmed SARS-CoV-2 presenting to Tygerberg Hospital, Cape Town, between 17 April and 24 July 2020. Results One hundred fifty-nine children (median age, 48.0 months [interquartile range {IQR}, 12.0–106.0 months]) were included. Hospitalized children (n = 62), with a median age of 13.5 months (IQR, 1.8–43.5 months) were younger than children not admitted (n = 97; median age, 81.0 months [IQR, 34.5–120.5 months]; P < .01.). Thirty-three of 159 (20.8%) children had preexisting medical conditions. Fifty-one of 62 (82.3%) hospitalized children were symptomatic; lower respiratory tract infection was diagnosed in 21 of 51 (41.2%) children, and in 11 of 16 (68.8%) children <3 months of age. Respiratory support was required in 25 of 51 (49.0%) children; 13 of these (52.0%) were <3 months of age. One child was HIV infected and 11 of 51 (21.2%) were HIV exposed but uninfected, and 7 of 51 (13.7%) children had a recent or new diagnosis of tuberculosis. Conclusions Children <1 year of age hospitalized with SARS-CoV-2 in Cape Town frequently required respiratory support. Access to oxygen may be limited in some low- and middle-income countries, which could potentially drive morbidity and mortality. HIV infection was uncommon but a relationship between HIV exposure, tuberculosis, and SARS-CoV-2 should be explored.
Generation of Mesenchymal Stromal Cells with Low Immunogenicity from Human PBMC-Derived β2 Microglobulin Knockout Induced Pluripotent Stem Cells

Mesenchymal stromal cells (MSCs) are viewed as immune-privileged cells and have been broadly applied in allogeneic adoptive cell transfer for regenerative medicine or immune-suppressing purpose. However, the surface expression of human leukocyte antigen (HLA) class I molecules on MSCs could still possibly induce the rejection of allogeneic MSCs from the recipients. Here, we disrupted the β2 microglobulin (B2M) gene in human peripheral blood mononuclear cell-derived induced pluripotent stem cells (iPSCs) with two clustered regulatory interspaced short palindromic repeat (CRISPR)-associated Cas9 endonuclease-based methods. The B2M knockout iPSCs did not express HLA class I molecules but maintained their pluripotency and genome stability. Subsequently, MSCs were derived from the HLA-negative iPSCs (iMSCs). We demonstrated that B2M knockout did not affect iMSC phenotype, multipotency, and immune suppressive characteristics and, most importantly, reduced iMSC immunogenicity to allogeneic peripheral blood mononuclear cells. Thus, B2M knockout iPSCs could serve as unlimited off-the-shelf cell resources in adoptive cell transfer, while the derived iMSCs hold great potential as universal grafts in allogeneic MSC transplantation.
Recent Advances in Synthesis, Bioactivity, and Pharmacokinetics of Pterostilbene, an Important Analog of Resveratrol

Pterostilbene is a natural 3,5-dimethoxy analog of resveratrol. This stilbene compound has a strong bioactivity and exists widely in Dalbergia and Vaccinium spp. Besides natural extraction, pterostilbene can be obtained by biosynthesis. Pterostilbene has become popular because of its remarkable pharmacological activities, such as anti-tumor, anti-oxidation, anti-inflammation, and neuroprotection. Pterostilbene can be rapidly absorbed and is widely distributed in tissues, but it does not seriously accumulate in the body. Pterostilbene can easily pass through the blood-brain barrier because of its low molecular weight and good liposolubility. In this review, the studies performed in the last three years on resources, synthesis, bioactivity, and pharmacokinetics of pterostilbene are summarized. This review focuses on the effects of pterostilbene on certain diseases to explore its targets, explain the possible mechanism, and look for potential therapeutic applications.
Biaryl Sulfonamides Based on the 2-Azabicycloalkane Skeleton—Synthesis and Antiproliferative Activity

In a search for new, selective antitumor agents, we prepared a series of sulfonamides built on bicyclic scaffolds of 2-azabicyclo(2.2.1)heptane and 2-azabicyclo(3.2.1)octane. To this end, aza-Diels–Alder cycloadducts were converted into amines bearing 2-azanorbornane or a bridged azepane skeleton; their treatment with sulfonyl chlorides containing biaryl moieties led to the title compounds. The study of antiproliferative activity of the new agents showed that some of them inhibited the growth of chosen cell lines with the IC50 values comparable with cisplatin, and some derivatives were found considerably less toxic for nonmalignant cells.
Intestinal Health and Threonine Requirement of Growing Pigs Fed Diets Containing High Dietary Fibre and Fermentable Protein

Simple Summary Dietary components, such as fibre and protein, have significant impacts on nutrient requirements and intestinal health in pigs. The objectives of this study were to investigate the interactive effects of dietary fibre and fermentable protein on threonine requirement for protein deposition in growing pigs and to determine how these factors affect markers of intestinal health. In this study we used the nitrogen-balance approach to study the influence of high protein diets combined with high fibre on threonine requirement for protein deposition. We further used gene expression, fermentation metabolites (short and branched chain fatty acid concentration), and serum antioxidant status in these pigs as markers of intestinal health and function. We demonstrate that high fibre will indeed increase threonine requirement for protein deposition but can mitigate the negative effects of fermentable protein metabolites on intestinal health. These results will have implications for the development of dietary strategies to improve growth and overall health in pigs, including adjustments to dietary fibre, protein, and amino acid content that maximize pig growth, nutrient utilization, and intestinal health. Abstract Dietary fibre (DF) and fermentable crude protein (fCP) are dietary factors which affect nutrient utilization and intestinal health in pigs. A nitrogen (N)-balance study was conducted to determine the impact of DF and fCP on threonine (Thr) requirement for protein deposition (PD) and indicators of intestinal health. A total of 160 growing pigs (25 kg) were randomly assigned to 1 of 20 dietary treatments in a 2 × 2 × 5 factorial arrangement in a randomized complete block design with dietary fibre (low (LF) or high fibre (HF)], fCP [low (LfCP) or high fCP (HfCP)) and Thr (0.52, 0.60, 0.68, 0.76, or 0.82% standardized ileal digestible) as factors. Then, 4-day total urine and fecal collection was conducted, and pigs were euthanized for intestinal tissue and digesta sampling. Feeding high DF, regardless of fCP content, increased Thr requirement for PD (p < 0.05). High fCP, regardless of DF content, reduced Thr requirement for PD. Serum antioxidant capacity increased as dietary Thr level increased (p < 0.05). Cecal digesta short-chain fatty acids (SCFA) increased (p < 0.05) with HF and branched-chain fatty acids (BCFA) increased with HfCP and reduced with HF (p < 0.05). HfCP reduced (p < 0.05) mucin-2 (MUC2) expression in the colon of the HF but not the LF fed pigs and HF increased MUC2 in the LfCP but not the HfCP fed pigs. Feeding HF diet increased (p < 0.05) expression of zonula occludens-1 in the LfCP with no effect on HfCP fed pigs. Ammonia concentration in both cecum and colon increased (p < 0.05) in the HfCP fed pigs. Overall, high DF reduced the negative impact of HfCP on intestinal health, as indicated by alterations in SCFA and BCFA production and gut barrier gene expression. While increased dietary Thr content is required for PD in pigs fed high DF, feeding high fCP reduced Thr requirements.
A review of the spinycheek sleepers, genus Eleotris (Teleostei: Eleotridae), of the western Hemisphere, with comparison to the west African species

Species of the genus Eleotris from the eastern Pacific and western Atlantic are reviewed. Three species are recognized from the eastern Pacific region. The wide-ranging Eleotris picta Kner, Eleotris tubularis Heller and Snodgrass (endemic to Cocos Island), and Eleotris tecta Bussing (limited to Costa Rica, Panama and Colombia) are distinguishable by scale counts (size), cephalic neuromast features and morphology of the urogenital papilla. Three western Atlantic species are recognized. Eleotris pisonis (Gmelin) is a continental South American species ranging from southern Brazil to the Orinoco River delta in eastern Venezuela. A second primarily continental species, E. amblyopsis (Cope), is distributed from Brazil through the Caribbean basin and Gulf of Mexico to North Carolina. Eleotris perniger (Cope), largely Caribbean in distribution, is the prevalent species in the Antilles and Quintana Roo, but is also sympatric with E. amblyopsis in Central America. The three western Atlantic species differ in scale counts and cephalic neuromast patterns. Eleotris daganensis Steindachner of West Africa is morphologically indistinguishable from E. amblyopsis. Lacking evidence of connectivity between eastern Atlantic populations of E. daganensis and western Atlantic populations of E. amblyopsis, the species are not synonymized. Eleotris annobonensis Blanc, Cadenat and Stauch is similar to E. perniger and North American populations of Eleotris amblyopsis. The remaining three West African species of Eleotris are most closely related to E. picta of the eastern Pacific. Eleotris and Erotelis are recognized as distinct genera. Tulane Studies in Zoology and Botany 32:12-##, 2001.
Hyaluronan: Metabolism and Function

As a major polysaccharide component of the extracellular matrix, hyaluronan plays essential roles in the organization of tissue architecture and the regulation of cellular functions, such as cell proliferation and migration, through interactions with cell-surface receptors and binding molecules. Metabolic pathways for biosynthesis and degradation tightly control the turnover rate, concentration, and molecular size of hyaluronan in tissues. Despite the relatively simple chemical composition of this polysaccharide, its wide range of molecular weights mediate diverse functions that depend on molecular size and tissue concentration. Genetic engineering and pharmacological approaches have demonstrated close associations between hyaluronan metabolism and functions in many physiological and pathological events, including morphogenesis, wound healing, and inflammation. Moreover, emerging evidence has suggested that the accumulation of hyaluronan extracellular matrix and fragments due to the altered expression of hyaluronan synthases and hyaluronidases potentiates cancer development and progression by remodeling the tumor microenvironment. In addition to the well-known functions exerted by extracellular hyaluronan, recent metabolomic approaches have also revealed that its synthesis can regulate cellular functions via the reprogramming of cellular metabolism. This review highlights the current advances in knowledge on the biosynthesis and catabolism of hyaluronan and describes the diverse functions associated with hyaluronan metabolism.
Doctors documenting: an ethnographic and informatics approach to understanding attending physician documentation in the pediatric emergency department

OBJECTIVE The pediatric emergency department is a highly complex and evolving environment. Despite the fact that physicians spend a majority of their time on documentation, little research has examined the role of documentation in provider workflow. The aim of this study is to examine the task of attending physician documentation workflow using a mixed-methods approach including focused ethnography, informatics, and the Systems Engineering Initiative for Patient Safety (SEIPS) model as a theoretical framework. MATERIALS AND METHODS In a 2-part study, we conducted a hierarchical task analysis of patient flow, followed by a survey of documenting ED providers. The second phase of the study included focused ethnographic observations of ED attendings which included measuring interruptions, time and motion, documentation locations, and qualitative field notes. This was followed by analysis of documentation data from the electronic medical record system. RESULTS Overall attending physicians reported low ratings of documentation satisfaction; satisfaction after each shift was associated with busyness and resident completion. Documentation occurred primarily in the provider workrooms, however strategies such as bedside documentation, dictation, and multitasking with residents were observed. Residents interrupted attendings more often but also completed more documentation actions in the electronic medical record. DISCUSSION Our findings demonstrate that complex work processes such as documentation, cannot be measured with 1 single data point or statistical analysis but rather a combination of data gathered from observations, surveys, comments, and thematic analyses. CONCLUSION Utilizing a sociotechnical systems framework and a mixed-methods approach, this study provides a holistic picture of documentation workflow. This approach provides a valuable foundation not only for researchers approaching complex healthcare systems but also for hospitals who are considering implementing large health information technology projects.
Experiences and expectations of obese older people on the care received in the primary health care network.

OBJECTIVE to understand the experiences and expectations of obese elderly people on the care they received in the primary health care network. METHODS phenomenological study, in which 16 obese elderly people living in a municipality in the state of Minas Gerais, Brazil, were interviewed. Their statements were organized into categories and analyzed according to Alfred Schütz's social phenomenology and thematic literature. RESULTS the following categories emerged: "Care neglected to obese elderly people in the primary health care network", "Group activities as a way to provide primary health care to obese elderly people: a present past", and "Qualified longitudinal care, centered in the needs of obese elderly people". FINAL CONSIDERATIONS offering comprehensive and longitudinal primary health care to obese older people was difficult, and there was instability in the consolidation of public policies, which pointed out the need for effective bonds between different healthcare network services and between professionals and users.
Acute Physiological Responses to High-Intensity Resistance Circuit Training vs. Traditional Strength Training in Soccer Players

Simple Summary Strength training is a key factor for soccer players, but at amateur levels, it is difficult to apply due to the lack of infrastructure and short training time. In this regard, high-intensity resistance circuit-based training could be a suitable method to solve these issues. Circuit training can improve the cardiorespiratory and metabolic responses while reducing training time by 66%. The effects of circuit training could contribute to improving aerobic fitness and body composition in soccer players. Abstract The aim of this study was to evaluate and compare the cardiorespiratory and metabolic responses induced by high-intensity resistance circuit-based (HRC) and traditional strength (TS) training protocols. Ten amateur soccer players reported to the laboratory on four occasions: (1) protocol familiarization and load determination; (2) maximal oxygen consumption test; (3) and (4) resistance training protocols (HRC and TS), completed in a cross-over randomized order. In both protocols, the same structure was used (two blocks of 3 sets × 3 exercises, separated by a 5-min rest), with only the time between consecutive exercises differing: TS (3 min) and HRC (~35 s, allowing 3 min of local recovery). To test for between-protocol differences, paired t-tests were applied. Results showed that oxygen consumption and heart rate during HRC were 75% and 39% higher than TS, respectively (p < 0.001). After the training sessions, blood lactate concentration at 1.5, 5 and 7 min and excess post-exercise oxygen consumption were higher in HRC. The respiratory exchange ratio was 6.7% greater during HRC, with no between-group differences found post-exercise. The energy cost of HRC was ~66% higher than TS. In conclusion, HRC training induces greater cardiorespiratory and metabolic responses in soccer players and thus may be a time-effective training strategy.
Focus on ROS1-Positive Non-Small Cell Lung Cancer (NSCLC): Crizotinib, Resistance Mechanisms and the Newer Generation of Targeted Therapies

Simple Summary Genetic rearrangements of the ROS1 gene account for up to 2% of NSCLC patients who sometimes develop brain metastasis, resulting in poor prognosis. This review discusses the tyrosine kinase inhibitor crizotinib plus updates and preliminary results with the newer generation of tyrosine kinase inhibitors, which have been specifically conceived to overcome crizotinib resistance, including brigatinib, cabozantinib, ceritinib, entrectinib, lorlatinib and repotrectinib. After introducing each agent’s properties, we provide suggestions on the best approaches to identify resistance mechanisms at an early stage, and we speculate on the most appropriate second-line therapies for patients who reported disease progression following crizotinib administration. Abstract The treatment of patients affected by non-small cell lung cancer (NSCLC) has been revolutionised by the discovery of druggable mutations. ROS1 (c-ros oncogene) is one gene with druggable mutations in NSCLC. ROS1 is currently targeted by several specific tyrosine kinase inhibitors (TKIs), but only two of these, crizotinib and entrectinib, have received Food and Drug Administration (FDA) approval. Crizotinib is a low molecular weight, orally available TKI that inhibits ROS1, MET and ALK and is considered the gold standard first-line treatment with demonstrated significant activity for lung cancers harbouring ROS1 gene rearrangements. However, crizotinib resistance often occurs, making the treatment of ROS1-positive lung cancers more challenging. A great effort has been undertaken to identify a new generation or ROS1 inhibitors. In this review, we briefly introduce the biology and role of ROS1 in lung cancer and discuss the underlying acquired mechanisms of resistance to crizotinib and the promising new agents able to overcome resistance mechanisms and offer alternative efficient therapies.
Combining optimization and simulation modelling to measure the cumulative impacts of prescribed fire and wildfire on vegetation species diversity

1. Growth-stage optimization (GSO) offers a new approach to biodiversity conservation in fire-prone regions by estimating the optimal distribution of vegetation growth stages that maximize a species diversity index. This optimal growth-stage structure provides managers an operational goal explicitly linked to a positive conservation outcome but does not define the fire regime needed to achieve it. 2. We paired GSO with LANDIS II, a landscape succession and disturbance simulation model, to (a) estimate the optimal growth-stage structure that maximized vegetation diversity in a south-east Australian heathy woodland, (b) define the fire regime needed to achieve it, and (c) determine the cumulative effects of different fire-regime scenarios on vegetation diversity over a 60-year period. Scenarios included 0%, 2%, 5%, and 10% of the landscape burnt per year by prescribed fire only, or in combination with three alternative wildfire regimes. Furthermore, we investigated the differences in the optimal growth-stage structure relating to above-ground, soil seedbank, and total (above and soil seedbank) diversity datasets. 3.
On the Use of Biobased Waxes to Tune Thermal and Mechanical Properties of Polyhydroxyalkanoates–Bran Biocomposites

In this work, processability and mechanical performances of bio-composites based on poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) containing 5, 10, and 15 wt % of bran fibers, untreated and treated with natural carnauba and bee waxes were evaluated. Wheat bran, the main byproduct of flour milling, was used as filler to reduce the final cost of the PHBV-based composites and, in the same time, to find a potential valorization to this agro-food by-product, widely available at low cost. The results showed that the wheat bran powder did not act as reinforcement, but as filler for PHBV, due to an unfavorable aspect ratio of the particles and poor adhesion with the polymeric matrix, with consequent moderate loss in mechanical properties (tensile strength and elongation at break). The surface treatment of the wheat bran particles with waxes, and in particular with beeswax, was found to improve the mechanical performance in terms of tensile properties and impact resistance of the composites, enhancing the adhesion between the PHBV-based polymeric matrix and the bran fibers, as confirmed by predictive analytic models and dynamic mechanical analysis results.