Miracle-dz/UniFAR-FTUs huggingface dataset:
Advanced Formulation Approaches for Ocular Drug Delivery: State-Of-The-Art and Recent Patents

The eye presents extensive perspectives and challenges for drug delivery, mainly because of the extraordinary capacity, intrinsic to this path, for drugs to permeate into the main circulatory system and also for the restrictions of the ocular barriers. Depending on the target segment of the eye, anterior or posterior, the specifications are different. The ocular route experienced in the last decades a lot of progresses related with the development of new drugs, improved formulations, specific-designed delivery and even new routes to administer a drug. Concomitantly, new categories of materials were developed and adapted to encapsulate drugs. With such advances, a multiplicity of parameters became possible to be optimized as the increase in bioavailability and decreased toxic effects of medicines. Also, the formulations were capable to easily adhere to specific tissues, increase the duration of the therapeutic effect and even target the delivery of the treatment. The ascending of new delivery systems for ocular targeting is a current focus, mainly because of the capacity to extend the normal time during which the drug exerts its therapeutic effect and, so, supplying the patients with a product which gives them fewer side effects, fewer number of applications and even more effective outcomes to their pathologies, surpassing the traditionally-used eye drops. Depending on the systems, some are capable of increasing the duration of the drug action as gels, emulsions, prodrugs, liposomes, and ocular inserts with hydrophilic properties, improving the absorption by the cornea. In parallel, other devices use as a strategy the capacity to sustain the release of the carried drugs by means of erodible and non-erodible matrices. This review discusses the different types of advanced formulations used for ocular delivery of therapeutics presenting the most recent patents according to the clinical applications.
Pediatric Pulmonology

Funding information Foundation for the National Institutes of Health, Grant/Award Number: T32 HL 72748‐ 16 A1 Abstract Introduction: The purpose of this study was to examine the clinical features/ outcomes associated with tracheostomy in infants with congenital diaphragmatic hernia (CDH). Methods: The study population consisted of liveborn infants reported to the CDH Study Group registry between 2007 and 2017. Subjects were identified as having a tracheostomy if they were discharged or transferred to another hospital with tracheostomy and/or on mechanical ventilation. Multivariate mixed models were used for analyses. Results: The registry population consisted of 5434 subjects, of whom 230 (4.2%) underwent tracheostomy placement. Only 3830 (70.5%) infants survived until discharge/transfer. The median age of tracheostomy placement was 3.3 months (range, 1.3‐13.4 when known; n = 58 out of 154 survivors). The mortality rate among subjects with tracheostomy was 32.8% with a median of 37 days (range, 8‐189 when known; n = 32 out of 75 deceased) ensuing between tracheostomy placement and death. The clinical features found to be associated with increased odds ratio of tracheostomy placement included male sex, birth weight, 5‐minute APGAR score, defect size, liver in chest, ECMO use, cardiac abnormality, other congenital abnormalities, pulmonary hypertension, and the presence of a feeding tube. There was center variation in the rate of tracheostomy placement, which may be partially accounted for by disease severity, but not center size. Conclusion: There are several clinical features that are associated with increased likelihood of tracheostomy placement. Most deaths in subjects with tracheostomies occurred outside the immediate postoperative period. The utility of a standardized protocol for tracheostomy in infants with CDH should be considered.
Elevated zinc transporter ZnT3 in the dentate gyrus of mast cell‐deficient mice

Zinc is important in neurogenesis, but excessive levels can cause apoptosis and other pathologies leading to cognitive impairments. Mast cells are present in many brain regions including the hippocampus, an area rich in vesicular zinc. Mast cells contain zinc‐rich granules and a well‐developed mechanism for uptake of zinc ions; both features point to the potential for a role in zinc homeostasis. Prior work using the Timm stain supported this hypothesis, as increased labile zinc was detected in the hippocampus of mast cell‐deficient mice compared to wild‐type mice while no differences in total zinc were found between the two genotypes in the whole brain or other tissues. The current report further examines differences in zinc homeostasis between wild‐type and mast cell‐deficient mice by exploring the zinc transporter ZnT3, which transports labile zinc into synaptic vesicles. The first study used immunocytochemistry to localize ZnT3 within the mossy fibre layer of the hippocampus to determine whether there was differential expression of ZnT3 in wild‐type versus mast cell‐deficient mice. The second study used inductively coupled plasma mass spectrometry (ICP‐MS) to determine total zinc content in the whole dentate gyrus of the two genotypes. The immunocytochemical results indicate that there are higher levels of ZnT3 localized to the mossy fibre layer of the dentate gyrus of mast cell‐deficient mice than in wild‐type mice. The ICP‐MS data reveal no differences in total zinc in dentate gyrus as a whole. The results are consistent with the hypothesis that mast cells participate in zinc homeostasis at the level of synaptic vesicles.
Automatic Sitting Pose Generation for Ergonomic Ratings of Chairs

Human poses play a critical role in human-centric product design. Despite considerable researches on pose synthesis and pose-driven product design, most of them adopt the simple stick figure model that captures only skeletons rather than real body geometries and do not link human poses to the environment (e.g., chairs for sitting). This paper focuses on user-tailored ergonomic design and rating of chairs using scanned human geometries. Fully utilizing the anthropometric information of the human models, our method considers more ergonomic guidelines of chair design (such as pressure distribution and support intensity) and links the geometry of 3D chair models and human-to-chair interactions into the pose deformation constraints of the human avatars. The core of our method is a pose generation algorithm which rigs the user's successive poses through coarse- and fine-level pose deformations. We define a non-linear energy function with contact, collision, and joint limit terms, and solve it using a hill-climbing algorithm. The fitting results allow us to quantitatively evaluate the chair model in terms of various ergonomic criteria. Our method is flexible and effective and can be applied to users with varying body shapes and a wide range of chairs. Moreover, the proposed technique can be easily extended to other furniture, such as desk, bed, and cabinet. Extensive evaluations and a user study demonstrate the efficiency and advantages of the proposed virtual fitting method. Given that our method avoids tedious on-site trying, facilitates the exploration/evaluation of various chair products, and provides valuable feedback for the designers and manufacturers to deliver customized products, it is ideal for online shopping of chairs.
Trauma-associated acute kidney injury.

PURPOSE OF REVIEW A summary of recent research into the epidemiology, cause, management and outcomes of trauma-associated acute kidney injury (AKI). There is an increasing focus on subtypes of AKI to better target clinical management and future research. RECENT FINDINGS AKI associated with trauma occurs in 20-24% of patients admitted to ICU. On the basis of creatinine and/or urine output, AKI occurs in the first few days of traumatic illness. Although various associations have been identified, shock and high-volume blood transfusion are the most consistent risks for development of trauma-associated AKI. Short-term outcomes appear worse for patients with AKI, but extent of longer term kidney function recovery remains unknown. Recent research in the general critical care population is beginning to better inform AKI management; however, currently, preventive and supportive strategies remain the mainstay of AKI management after trauma. SUMMARY Well-designed, prospective research is required to better understand the phenotype, pathophysiology and recovery trajectory of trauma-associated AKI. Only then can potentially unique therapeutic targets be developed for this common subtype of AKI.
Development of a patient safety culture scale for maternal and child health institutions in China: a cross-sectional validation study

Objective This study aimed to develop a patient safety culture (PSC) scale for maternal and child healthcare (MCH) institutions in China. Methods A theoretical framework of PSC for MCH institutions was proposed through in-depth interviews with MCH workers and patients and Delphi expert consultations. The reliability and validity of the PSC scale were tested in a cross-sectional survey of 1256 MCH workers from 14 MCH institutions in Zhejiang province of China. The study sample was randomly split into half for exploratory and confirmatory factor analyses, respectively. Test–retest reliability was assessed through a repeated survey of 63 voluntary participants 2 weeks apart. Results The exploratory factor analysis extracted 10 components: patient engagement in patient safety (six items), managerial response to patient safety risks (four items), perceived management support (five items), staff empowerment (four items), staffing and workloads (four items), reporting of adverse events (three items), defensive medical practice (three items), work commitment (three items), training (two items) and transfer and handoff (three items). A good model fit was found in the confirmatory factor analysis: χ2/df=1.822, standardised root mean residual=0.048, root mean square error of approximation=0.038, comparative fit index=0.921, Tucker-Lewis index=0.907. The PSC scale had a Cronbach’s α coefficient of 0.89 (0.59–0.90 for dimensional scales) and a test–retest reliability of 0.81 (0.63–0.87 for dimensional reliability), respectively. The intracluster correlation coefficients confirmed a hierarchical nature of the data: individual health workers nested within MCH institutions. Conclusion The PSC scale for MCH institutions has acceptable reliability and validity. Further studies are needed to establish benchmarking in a national representative sample through a multilevel modelling approach.
Trust Relationship Prediction in Alibaba E-Commerce Platform

This paper introduces how to infer trust relationships from billion-scale networked data to benefit Alibaba E-Commerce business. To effectively leverage the network correlations between labeled and unlabeled relationships to predict trust relationships, we formalize trust into multiple types and propose a graphical model to incorporate type-based dyadic and triadic correlations, namely eTrust. We also present a fast learning algorithm in order to handle billion-scale networks. Systematically, we evaluate the proposed methods on four different genres of datasets with labeled trust relationships: Alibaba, Epinions, Ciao, and Advogato. Experimental results show that the proposed methods achieve significantly better performance than several comparison methods (+1.7-32.3% by accuracy; <inline-formula><tex-math notation="LaTeX">$p<<0.01$</tex-math><alternatives><mml:math><mml:mrow><mml:mi>p</mml:mi><mml:mo><</mml:mo><mml:mo><</mml:mo><mml:mn>0</mml:mn><mml:mo>.</mml:mo><mml:mn>01</mml:mn></mml:mrow></mml:math><inline-graphic xlink:href="zhang-ieq1-2893939.gif"/></alternatives></inline-formula>, with <inline-formula><tex-math notation="LaTeX">$t$</tex-math><alternatives><mml:math><mml:mi>t</mml:mi></mml:math><inline-graphic xlink:href="zhang-ieq2-2893939.gif"/></alternatives></inline-formula>-test). Most importantly, when handling the real large networked data with over 1,200,000,000 edges (Ali-large), our method achieves 2,000× speedup to infer trust relationships, comparing with the traditional graph learning algorithms. Finally, we have applied the inferred trust relationships to Alibaba E-commerce platform: Taobao, and achieved 2.75 percent improvement on gross merchandise volume (GMV).
Test Your Memory (TYM) and Test Your Memory for Mild Cognitive Impairment (TYM-MCI): A Review and Update Including Results of Using the TYM Test in a General Neurology Clinic and Using a Telephone Version of the TYM Test

This paper summarises the current status of two novel short cognitive tests (SCT), known as Test Your Memory (TYM) and Test Your Memory for Mild Cognitive Impairment (TYM-MCI). The history of and recent research on the TYM and TYM-MCI are summarised in applications for Alzheimer’s and non-Alzheimer’s dementia and mild cognitive impairment. The TYM test can be used in a general neurology clinic and can help distinguish patients with Alzheimer’s disease (AD) from those with no neurological cause for their memory complaints. An adapted tele-TYM test administered by telephone to patients produces scores which correlate strongly with the clinic-administered Addenbrookes Cognitive Examination revised (ACE-R) test and can identify patients with dementia. Patients with AD decline on the TYM test at a rate of 3.6–4.1 points/year.
Coelonin, an Anti-Inflammation Active Component of Bletilla striata and Its Potential Mechanism

Ethanol extract of Bletilla striata has remarkable anti-inflammatory and anti-pulmonary fibrosis activities in the rat silicosis model. However, its active substances and molecular mechanism are still unclear. To uncover the active ingredients and potential molecular mechanism of the Bletilla striata extract, the lipopolysaccharide (LPS)-induced macrophage inflammation model and phospho antibody array were used. Coelonin, a dihydrophenanthrene compound was isolated and identified. It significantly inhibited LPS-induced interleukin-1β (IL-1β), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) expression at 2.5 μg/mL. The microarray data indicate that the phosphorylation levels of 32 proteins in the coelonin pre-treated group were significantly down-regulated. In particular, the phosphorylation levels of the key inflammatory regulators factor nuclear factor-kappa B (NF-κB) were significantly reduced, and the negative regulator phosphatase and tensin homologue on chromosome ten (PTEN) was reduced. Moreover, the phosphorylation level of cyclin dependent kinase inhibitor 1B (p27Kip1), another downstream molecule regulated by PTEN was also reduced significantly. Western blot and confocal microscopy results confirmed that coelonin inhibited LPS-induced PTEN phosphorylation in a dose-dependent manner, then inhibited NF-κB activation and p27Kip1 degradation by regulating the phosphatidylinositol-3-kinases/ v-akt murine thymoma viral oncogene homolog (PI3K/AKT) pathway negatively. However, PTEN inhibitor co-treatment analysis indicated that the inhibition of IL-1β, IL-6 and TNF-α expression by coelonin was independent of PTEN, whereas the inhibition of p27Kip1 degradation resulted in cell-cycle arrest in the G1 phase, which was dependent on PTEN. The anti-inflammatory activity of coelonin in vivo, which is one of the main active ingredients of Bletilla striata, deserves further study.
Prediction of Milk Coagulation Properties and Individual Cheese Yield in Sheep Using Partial Least Squares Regression

Simple Summary Considered that all sheep milk in Italy is destined for cheese processing, traits describing rennet coagulation aptitude should be among the most important selection goals for dairy breeds. To reduce the costs and logistics related to the large-scale recording of these traits, mid-infrared (MIR) spectroscopy could be conveniently used to generate reliable predictions without any additional cost. The aims of this research were to predict the milk coagulation properties (MCP) and individual cheese yield (ILCY) in sheep by MIR spectrometry using partial least squares regression (PLS), and to compare different data pre-treatment procedures. The prediction results observed in the present study, although moderate, suggest the possibility of adding novel phenotypes (e.g., MCP and ILCY) in breeding schemes for dairy sheep breeds. Mid-infrared spectroscopy coupled with PLS regression could allow the prediction of phenotypes at the population level without additional costs. Abstract The objectives of this study were (i) the prediction of sheep milk coagulation properties (MCP) and individual laboratory cheese yield (ILCY) from mid-infrared (MIR) spectra by using partial least squares (PLS) regression, and (ii) the comparison of different data pre-treatments on prediction accuracy. Individual milk samples of 970 Sarda breed ewes were analyzed for rennet coagulation time (RCT), curd-firming time (k20), and curd firmness (a30) using the Formagraph instrument; ILCY was measured by micro-manufacturing assays. An Furier-transform Infrared (FTIR) milk-analyzer was used for the estimation of the milk gross composition and the recording of MIR spectrum. The dataset (n = 859, after the exclusion of 111 noncoagulating samples) was divided into two sub-datasets: the data of 700 ewes were used to estimate prediction model parameters, and the data of 159 ewes were used to validate the model. Four prediction scenarios were compared in the validation, differing for the use of whole or reduced MIR spectrum and the use of raw or corrected data (locally weighted scatterplot smoothing). PLS prediction statistics were moderate. The use of the reduced MIR spectrum yielded the best results for the considered traits, whereas the data correction improved the prediction ability only when the whole MIR spectrum was used. In conclusion, PLS achieves good accuracy of prediction, in particular for ILCY and RCT, and it may enable increasing the number of traits to be included in breeding programs for dairy sheep without additional costs and logistics.
Structure of a Synthetic β-Carboxysome Shell1[OPEN]

The high-resolution cryo-EM structure of a synthetic β-carboxysome shell reveals the specific protein interactions and assists in future study of permeability and encapsulation properties. Carboxysomes are capsid-like, CO2-fixing organelles that are present in all cyanobacteria and some chemoautotrophs and that substantially contribute to global primary production. They are composed of a selectively permeable protein shell that encapsulates Rubisco, the principal CO2-fixing enzyme, and carbonic anhydrase. As the centerpiece of the carbon-concentrating mechanism, by packaging enzymes that collectively enhance catalysis, the carboxysome shell enables the generation of a locally elevated concentration of substrate CO2 and the prevention of CO2 escape. A functional carboxysome consisting of an intact shell and cargo is essential for cyanobacterial growth under ambient CO2 concentrations. Using cryo-electron microscopy, we have determined the structure of a recombinantly produced simplified β-carboxysome shell. The structure reveals the sidedness and the specific interactions between the carboxysome shell proteins. The model provides insight into the structural basis of selective permeability of the carboxysome shell and can be used to design modifications to investigate the mechanisms of cargo encapsulation and other physiochemical properties such as permeability. Notably, the permeability properties are of great interest for modeling and evaluating this carbon-concentrating mechanism in metabolic engineering. Moreover, we find striking similarity between the carboxysome shell and the structurally characterized, evolutionarily distant metabolosome shell, implying universal architectural principles for bacterial microcompartment shells.
Regenerative treatment with umbilical cord mesenchymal stem cells from Wharton's jelly in chronic ulcer caused by dermolipectomy.

Background Procedures to remove adiposities and skin, such as dermolipectomy, can develop wounds that are difficult to heal by conventional therapies. Mesenchymal stem cells are indicated as potential candidates for regenerative therapy in wounds, due to their multipotentiality, low immunogenicity, modulating capacity of inflammation and tissue modeling processes. Case report Patient with dehiscent chronic ulcer secondary to dermolipectomy, who received cutaneous treatment with mesenchymal stem cells. The therapy induced scar formation and neovascularization, as well as the decrease of infiltrated leukocytes and proinflammatory cytokines. Mesenchymal cells are proposed as an interesting alternative for the treatment of postoperative lesions.
Type and case volume of health care facility influences survival and surgery selection in cases with early‐stage non–small cell lung cancer

With the expansion of non–small cell lung cancer (NSCLC) screening methods, the percentage of cases with early‐stage NSCLC is anticipated to increase. Yet it remains unclear how the type and case volume of the health care facility at which treatment occurs may affect surgery selection and overall survival for cases with early‐stage NSCLC.
Interpreting neonatal hip sonography: intraobserver and interobserver variability

The purpose of this study is to state the reliability of neonatal hip ultrasound interpretation, defining the intra and interoperator variability in the evaluation of the scans. We considered a sample of 2071 scans (coming from 798 patients who attended the screening programme for hip dysplasia), which were interpreted by the operator who obtained and read the images at the screening time and then by a different operator who saw the images for the first time. Both the intra and interoperator variability of α and β angles’ values resulted statistically not significative (intraclass correlation coefficient > 0.8) and determining a class shift (according to the Graf’s classification) in a nonstatistically significative number of cases (agreement percentage >91% and Cohen’s κ >0.8). Hip sonography can reliably detect hip dysplasia and the intra and interoperator variability in the interpretation of the exam is NS when the examination is correctly executed.
Reusing Information for Multifidelity Active Learning in Reliability-Based Design Optimization

This paper develops a multifidelity method to reuse information from optimization history for adaptively refining surrogates in reliability-based design optimization (RBDO). RBDO can be computationally prohibitive due to numerous evaluations of the expensive high-fidelity models to estimate the probability of failure of the system in each optimization iteration. In this work, the high-fidelity model evaluations are replaced by cheaper-to-evaluate adaptively refined surrogate evaluations in the probability of failure estimation. The method reuses the past optimization iterations as an information source for devising an efficient multifidelity active learning (adaptive sampling) algorithm to refine the surrogates that best locate the failure boundary. We implement the information-reuse method using a multifidelity extension of efficient global reliability analysis that combines the expected feasibility function with a weighted lookahead information gain criterion to pick both the next sample location and information source used to evaluate the sample.