Miracle-dz/UniFAR-FTUs huggingface dataset:
Enhancing the Extraction of Polysaccharides and Antioxidants from Macroalgae Using Sequential Hydrothermal-Assisted Extraction Followed by Ultrasound and Thermal Technologies

Fucose sulphated polysaccharides (FSPs) and glucans have recently attracted the attention of the scientific community due to their wide range of biological activities. Both polysaccharides should ideally be selectively extracted using innovative technologies with high extraction efficiency. This study aims to: (1) Optimise the extraction variables used in hydrothermal-assisted extraction (HAE) to obtain high yields of FSPs, total glucans, and antioxidants from Laminaria hyperborea; (2) to apply these optimised protocols to other brown macroalgae; and (3) to explore the application of ultrasound and thermal technologies to increase the recovery of polysaccharides from the residual biomass. Box-Behnken design (three-factor, four-levels) was employed to optimise the HAE variables, and principal component analysis was used to evaluate the recovery of polysaccharides from the residual biomass. The optimal HAE conditions were 120 °C, 80.9 min, and 12.02 mL/g macroalgae from L. hyperborea. The best sequential application of ultrasound and thermal treatment achieved an additional 2971.7 ± 61.9 mg fucose/100 g dried macroalgal residue (dmr) from Ascophyllum nodosum and 908.0 ± 51.4 mg total glucans/100 g dmr from L. hyperborea macroalgal residues.
Therapies for the management of genitourinary syndrome of menopause

Introduction The genitourinary syndrome of menopause is a new term that describes various menopausal symptoms and signs including not only genital symptoms (dryness, burning, and irritation) and sexual symptoms (lack of lubrication, discomfort or pain, and impaired function), but also urinary symptoms (urgency, dysuria, and recurrent urinary tract infections). Methods We conducted a systematic scoping review of data in women therapies with genitourinary syndrome of menopause or vulvovaginal atrophy in peer-reviewed, English-language publications in the last 20 years. Results The terms vulvovaginal atrophy and atrophic vaginitis, which were generally used up until recently, had a limitation because they did not cover the full spectrum of symptoms and did not imply that the symptoms are related to a decreased sex steroid level in menopause. The concept of genitourinary syndrome of menopause was recently introduced and has been gaining widespread use. Since genitourinary syndrome of menopause may have a profound negative impact on the quality of life of postmenopausal women, patients should be made aware of these problems and treated with an appropriate effective therapy. Therefore, in this review we introduce therapies for this syndrome, both local and systemic, and discuss the importance of genitourinary syndrome of menopause comprehension and the need to have an active treatment of this syndrome in postmenopausal women. Conclusion The increasing number of therapies for menopausal symptoms opens up new options. In addition, new products have been designed and developed by pharmaceutical companies as new possibilities for patients who did not have any treatment available and also to improve compliance.
Referral for Kidney Transplantation in Canadian Provinces.

BACKGROUND Patient referral to a transplant facility, a prerequisite for dialysis-treated patients to access kidney transplantation in Canada, is a subjective process that is not recorded in national dialysis or transplant registries. Patients who may benefit from transplant may not be referred. METHODS In this observational study, we prospectively identified referrals for kidney transplant in adult patients between June 2010 and May 2013 in 12 transplant centers, and linked these data to information on incident dialysis patients in a national registry. RESULTS Among 13,184 patients initiating chronic dialysis, the cumulative incidence of referral for transplant was 17.3%, 24.0%, and 26.8% at 1, 2, and 3 years after dialysis initiation, respectively; the rate of transplant referral was 15.8 per 100 patient-years (95% confidence interval, 15.1 to 16.4). Transplant referral varied more than three-fold between provinces, but it was not associated with the rate of deceased organ donation or median waiting time for transplant in individual provinces. In a multivariable model, factors associated with a lower likelihood of referral included older patient age, female sex, diabetes-related ESKD, higher comorbid disease burden, longer durations (>12.0 months) of predialysis care, and receiving dialysis at a location >100 km from a transplant center. Median household income and non-Caucasian race were not associated with a lower likelihood of referral. CONCLUSIONS Referral rates for transplantation varied widely between Canadian provinces but were not lower among patients of non-Caucasian race or with lower socioeconomic status. Standardization of transplantation referral practices and ongoing national reporting of referral may decrease disparities in patient access to kidney transplant.
Kinome-Wide Screening with Small Interfering RNA Identified Polo-like Kinase 1 as a Key Regulator of Proliferation in Oral Cancer Cells

Oral squamous cell carcinoma (OSCC) is one of the major leading causes of cancer-related death worldwide, with limited effective markers for diagnosis and therapy, which has caused a low overall survival rate in the past decades. Kinases play important roles in tumor development and malignancy in various types of cancer. However, little is known about the role of kinases in OSCC cells. In this study, an arrayed kinome small interfering RNA (siRNA) library was used to screen oral cancer cell lines and counter assayed with normal fibroblast cells to identify the genes required for cancer cell proliferation. We found that polo-like kinase 1 (PLK1) was one of the most potent genes required for OSCC cell proliferation. The knockdown of PLK1 with a siRNA or antisense oligonucleotide (ASO) consistently diminished cyclin-B1 (CCNB1) expression/phosphorylation and the G2-M phase transition. Similar effects were observed in cells treated with the PLK1 kinase inhibitor BI6727. Besides, The Cancer Genome Atlas (TCGA) analysis revealed that PLK1 was elevated in tumor tissues and associated with short survival in patients with OSCC. We also found that PLK1 expression was highly correlated with the expression of its downstream effector, CCNB1, in patients with OSCC. Coexpression of the two genes resulted in a poor prognosis of OSCC patients, particularly those in the advanced stages of OSCC. Taken together, our results suggest that PLK1 might be a diagnostic or therapeutic marker for OSCC.
A Machine Learning Algorithm to Predict Severe Sepsis and Septic Shock: Development, Implementation, and Impact on Clinical Practice.

OBJECTIVES Develop and implement a machine learning algorithm to predict severe sepsis and septic shock and evaluate the impact on clinical practice and patient outcomes. DESIGN Retrospective cohort for algorithm derivation and validation, pre-post impact evaluation. SETTING Tertiary teaching hospital system in Philadelphia, PA. PATIENTS All non-ICU admissions; algorithm derivation July 2011 to June 2014 (n = 162,212); algorithm validation October to December 2015 (n = 10,448); silent versus alert comparison January 2016 to February 2017 (silent n = 22,280; alert n = 32,184). INTERVENTIONS A random-forest classifier, derived and validated using electronic health record data, was deployed both silently and later with an alert to notify clinical teams of sepsis prediction. MEASUREMENT AND MAIN RESULT Patients identified for training the algorithm were required to have International Classification of Diseases, 9th Edition codes for severe sepsis or septic shock and a positive blood culture during their hospital encounter with either a lactate greater than 2.2 mmol/L or a systolic blood pressure less than 90 mm Hg. The algorithm demonstrated a sensitivity of 26% and specificity of 98%, with a positive predictive value of 29% and positive likelihood ratio of 13. The alert resulted in a small statistically significant increase in lactate testing and IV fluid administration. There was no significant difference in mortality, discharge disposition, or transfer to ICU, although there was a reduction in time-to-ICU transfer. CONCLUSIONS Our machine learning algorithm can predict, with low sensitivity but high specificity, the impending occurrence of severe sepsis and septic shock. Algorithm-generated predictive alerts modestly impacted clinical measures. Next steps include describing clinical perception of this tool and optimizing algorithm design and delivery.
Free-Water Imaging in White and Gray Matter in Parkinson’s Disease

This study aimed to discriminate between neuroinflammation and neuronal degeneration in the white matter (WM) and gray matter (GM) of patients with Parkinson’s disease (PD) using free-water (FW) imaging. Analysis using tract-based spatial statistics (TBSS) of 20 patients with PD and 20 healthy individuals revealed changes in FW imaging indices (i.e., reduced FW-corrected fractional anisotropy (FAT), increased FW-corrected mean, axial, and radial diffusivities (MDT, ADT, and RDT, respectively) and fractional volume of FW (FW) in somewhat more specific WM areas compared with the changes of DTI indices. The region-of-interest (ROI) analysis further supported these findings, whereby those with PD showed significantly lower FAT and higher MDT, ADT, and RDT (indices of neuronal degeneration) in anterior WM areas as well as higher FW (index of neuroinflammation) in posterior WM areas compared with the controls. Results of GM-based spatial statistics (GBSS) analysis revealed that patients with PD had significantly higher MDT, ADT, and FW than the controls, whereas ROI analysis showed significantly increased MDT and FW and a trend toward increased ADT in GM areas, corresponding to Braak stage IV. These findings support the hypothesis that neuroinflammation precedes neuronal degeneration in PD, whereas WM microstructural alterations precede changes in GM.
A comparative study of litter size and sex composition in a large dataset of callitrichine monkeys

In many birds and mammals, the size and sex composition of litters can have important downstream effects for individual offspring. Primates are model organisms for questions of cooperation and conflict, but the factors shaping interactions among same‐age siblings have been less‐studied in primates because most species bear single young. However, callitrichines (marmosets, tamarins, and lion tamarins) frequently bear litters of two or more, thereby providing the opportunity to ask whether variation in the size and sex composition of litters affects development, survival, and reproduction. To investigate these questions, we compiled a large dataset of nine species of callitrichines (n = 27,080 individuals; Callithrix geoffroyi, Callithrix jacchus, Cebuella pygmaea, Saguinus imperator, Saguinus oedipus, Leontopithecus chrysomelas, Leontopithecus chrysopygus, Leontopithecus rosalia, and Callimico goeldii) from zoo and laboratory populations spanning 80 years (1938–2018). Through this comparative approach, we found several lines of evidence that litter size and sex composition may impact fitness. Singletons have higher survivorship than litter‐born peers and they significantly outperform litter‐born individuals on two measures of reproductive performance. Further, for some species, individuals born in a mixed‐sex litter outperform isosexually‐born individuals (i.e., those born in all‐male or all‐female litters), suggesting that same‐sex competition may limit reproductive performance. We also document several interesting demographic trends. All but one species (C. pygmaea) has a male‐biased birth sex ratio with higher survivorship from birth to sexual maturity among females (although this was significant in only two species). Isosexual litters occurred at the expected frequency (with one exception: C. pygmaea), unlike other animals, where isosexual litters are typically overrepresented. Taken together, our results indicate a modest negative effect of same‐age sibling competition on reproductive output in captive callitrichines. This study also serves to illustrate the value of zoo and laboratory records for biological inquiry.
Dietary Curcumin Prevented Astrocytosis, Microgliosis, and Apoptosis Caused by Acute and Chronic Exposure to Ozone

Ozone is the most oxidant tropospheric pollutant gas, causing damage through the formation of reactive oxygen and nitrogen species. Reactive species induce the nuclear factor-kappa B (NF-κB) activation leading to neuroinflammation characterized by astrocytosis, microgliosis, and apoptotic cell death. There is interest in evaluating the pharmacological activity of natural antioxidants to confer neuroprotection against the damage caused by ozone in highly polluted cities. Curcumin has been proven to exert a protective action in the central nervous system (CNS) of diverse experimental models, with no side effects. The aim of this work is to evaluate the effect of curcumin in a preventive and therapeutic manner against the astrocytosis, microgliosis, and apoptosis induced by ozone in rat hippocampus. Fifty Wistar rats were distributed into five experimental groups: The intact control, curcumin fed control, ozone-exposed group, and the preventive and therapeutic groups receiving the curcumin supplementation while exposed to ozone. Ozone caused astrocytosis and microgliosis, as well as apoptosis in the hippocampus. Meanwhile, curcumin was able to decrease the activation of microglia and astrocytes, and apoptotic cell death in both periods of exposure. Therefore, we propose that curcumin could be used as a molecule capable of counteracting the damage caused by ozone in the CNS.
Possibilities of Fucoidan Utilization in the Development of Pharmaceutical Dosage Forms

Fucoidan is a polysaccharide built from L-fucose molecules. The main source of this polysaccharide is the extracellular matrix of brown seaweed (Phaeophyta), but it can be also isolated from invertebrates such as sea urchins (Echinoidea) and sea cucumbers (Holothuroidea). Interest in fucoidan is related to its broad biological activity, including possible antioxidant, anti-inflammatory, antifungal, antiviral or antithrombotic effects. The potential application of fucoidan in the pharmaceutical technology is also due to its ionic nature. The negative charge of the molecule results from the presence of sulfate residues in the C-2 and C-4 positions, occasionally in C-3, allowing the formation of complexes with other oppositely charged molecules. Fucoidan is non-toxic, biodegradable and biocompatible compound approved by Food and Drug Administration (FDA) as Generally Recognized As Safe (GRAS) category as food ingredient. Fucoidan plays an important role in the pharmaceutical technology, so in this work aspects concerning its pharmaceutical characteristics and designing of various dosage forms (nanoparticles, liposomes, microparticles, and semisolid formulations) with fucoidan itself and with its combinations with other polymers or components that give a positive charge were reviewed. Advantages and limitations of fucoidan utilization in the pharmaceutical technology were also discussed.
A proof‐of‐principle study comparing barrier function and cell morphology in face and body skin

The purpose of this pilot in vivo study was to investigate corneocyte size and transepidermal water loss (TEWL) in facial cheek and volar forearm skin as a function of consecutive tape stripping. Changes in corneocyte size and transepidermal water loss (TEWL) were measured as a function of stratum corneum (SC) depth at both anatomical sites. To our knowledge, this is the first published quantitative comparison based on these parameters. This work complements our previously published studies on face skin barrier recovery at 24 h and 4 weeks post‐tape stripping [Gorcea et al., Skin Res. Technol. , 19, 2013, e375‐e382; Gorcea et al., Int. J. Cosmet. Sci. 35, 2013, 250].
Effects of Developmental Task Constraints on Kinematic Synergies during Catching in Children with Developmental Delays

Abstract The aim of this study was to examine effects of a task intervention on kinematic synergies in catching. Participants were young children (5.58 ± 0.52 years) with the lowest scores on two-hand catching, according to assessments with the Test of Gross Motor Development-2 (TGMD-2) and were allocated into two groups. The constraints group took part in an 8-week intervention, whereas the control group experienced a typical physical education. Both groups were assessed with motor development and kinematic coordination measures with a catching task with a ball thrown from 2 m distance. Kinematic variables were recorded using a wireless motion capture system. A principal component analysis (PCA) was used to measure the kinematic synergies formed among active body parts. Two synergies that emerged in catching were mainly utilised for “reaching” and “catching” the ball. The control group tended to re-organise the majority of active body parts into two functional units in all phases, whereas the constraints group adapted their active parts into functional units according to the requirement of the novel movement in the transfer task. The findings of this study suggested that task constraints could facilitate object control by re-organisation of active body parts into functional synergies to achieve successful performance.
The dynamic relationship between pain, depression and cognitive function in a sample of newly diagnosed arthritic adults: a cross-lagged panel model

Abstract Background Pain and depression are common in the population and co-morbid with each other. Both are predictive of one another and are also associated with cognitive function; people who are in greater pain and more depressed respectively perform less well on tests of cognitive function. It has been argued that pain might cause deterioration in cognitive function, whereas better cognitive function earlier in life might be a protective factor against the emergence of disease. When looking at the dynamic relationship between these in chronic diseases, studying samples that already have advanced disease progression often confounds this relationship. Methods Using data from waves 1 to 3 of the English Longitudinal Study of Ageing (ELSA) (n = 516), we examined the interplay between pain, cognitive function and depression in a subsample of respondents reporting a diagnosis of arthritis at wave 2 of the ELSA using cross-lagged panel models. Results The models showed that pain, cognitive function and depression at wave 1, prior to diagnosis, predict pain at wave 2, and that pain at wave 1 predicts depression at wave 2. Pain and depression at wave 2 predict cognitive function at wave 3. Conclusions The results indicate that better cognitive function might be protective against the emergence of pain prior to an arthritis diagnosis, but cognitive function is subsequently impaired by pain and depression. Furthermore, higher depression predicts lower cognitive function, but not vice versa. This is discussed in the context of the emerging importance of inflammation in depression.
Measuring Work-Related Functioning Using the Work Rehabilitation Questionnaire (WORQ)

The assessment of work-related functioning is a key process in vocational rehabilitation to identify specific domains of disability that can be considered within return to work strategies. The Work Rehabilitation Questionnaire (WORQ) was developed to evaluate work-related functioning based on the International Classification of Functioning, Disability, and Health (ICF) framework and is available in different languages. The aim of this study was to assess the French version of the WORQ using item response theory to further validate the scale. Rasch analysis of WORQ and the WORQ-BRIEF (a brief version of the WORQ) was performed using a calibration sample of 221 persons with musculoskeletal injuries. A four-testlet solution indicated the unidimensionality of WORQ, with no differential item functioning for age, education, physical job demands, and injury severity. Reliability was 0.969 and 0.918 for WORQ and WORQ-BRIEF, respectively. The minimal detectable change was calculated to be 4.2% of its operational range for WORQ and 8.5% for WORQ-BRIEF. Consequently, the French version of WORQ can be considered a good measure of work-related functioning in musculoskeletal conditions. WORQ can be used in rehabilitation practice to comprehensively identify the disability and guide clinical decision making and intervention planning. Further studies are needed to evaluate the psychometric properties of WORQ in other health conditions.
New Era of Endoscopic Ultrasound-Guided Tissue Acquisition: Next-Generation Sequencing by Endoscopic Ultrasound-Guided Sampling for Pancreatic Cancer

Pancreatic cancer is a lethal cancer with an increasing incidence. Despite improvements in chemotherapy, patients with pancreatic cancer continue to face poor prognoses. Endoscopic ultrasound-guided tissue acquisition (EUS-TA) is the primary method for obtaining tissue samples of pancreatic cancer. Due to advancements in next-generation sequencing (NGS) technologies, multiple parallel sequencing can be applied to EUS-TA samples. Genomic biomarkers for therapeutic stratification in pancreatic cancer are still lacking, however, NGS can unveil potential predictive genomic biomarkers of treatment response. Thus, the importance of NGS using EUS-TA samples is becoming recognized. In this review, we discuss the recent advances in EUS-TA application for NGS of pancreatic cancer.
Environmentally persistent free radical (EPFR) formation by visible-light illumination of the organic matter in atmospheric particles.

A secondary process may be an important source of environmentally persistent free radicals (EPFRs) in atmospheric particulates, yet this process has remained to be elucidated. This study demonstrated that secondary EPFRs could be generated by visible-light illumination of atmospheric particulate matter (PM), and their lifetimes were only 30 min to 1 day, which were much shorter than the lifetimes of the original EPFRs in PM. The yields of secondary EPFRs produced by PM could reach 15% - 60% of those of the original EPFRs. The extractable organic matter contributed to the formation of secondary EPFRs (~55%), and a humic-like substance was the main precursor of the secondary EPFRs and was also the most productive precursor compared to the other aerosol components. The results of simulation experiments showed that the secondary EPFRs generated by the extractable and nonextractable PM components were similar to those produced by phenolic compounds and polycyclic aromatic hydrocarbons, respectively. We have found that oxygen molecules play an important role in the photochemical generation and decay of EPFRs. Reactive oxygen capture experiments showed that the original EPFRs may contribute to singlet oxygen generation, while the secondary EPFRs generated by photoexcitation may not produce singlet oxygen or hydroxyl radicals.
TP53I11 suppresses epithelial-mesenchymal transition and metastasis of breast cancer cells

Epithelial-mesenchymal transition (EMT) is widely-considered to be a modulating factor of anoikis and cancer metastasis. We found that, in MDA-MB-231 cells, TP53I11 (tumor protein P53 inducible protein 11) suppressed EMT and migration in vitro, and inhibited metastasis in vivo. Our findings showed that hypoxic treatment upregulated the expression of HIF1α, but reduced TP53I11 protein levels and TP53I11 overexpression reduced HIF1α expression under normal culture and hypoxicconditions, and in xenografts of MDA-MB-231 cells. Considering HIF1α is a master regulator of the hypoxic response and that hypoxia is a crucial trigger of cancer metastasis, our study suggests that TP53I11 may suppress EMT and metastasis by reducing HIF1α protein levels in breast cancer cells.