Miracle-dz/UniFAR-FTUs huggingface dataset:
Clinical Characterisation and Management of the Main Treatment-Induced Toxicities in Patients with Hepatocellular Carcinoma and Cirrhosis

Simple Summary The incidence of hepatocellular carcinoma continues to increase worldwide. In almost all cases, hepatocellular carcinoma develops in subjects with hepatic cirrhosis and patients can therefore present symptoms that are attributable to both conditions. There are several ablation techniques currently available for the treatment of unresectable HCC associated with early-stage cirrhosis. Moreover, novel therapies with biological agents and immunotherapy have come to be standard options in the approach to systemic treatment of hepatocellular carcinoma. However, in addition to being costly, these drugs are not devoid of adverse effects and their management cannot forgo the consideration of the underlying hepatic impairment. Therefore, these patients require a mandatory multidisciplinary management. Abstract The incidence of hepatocellular carcinoma (HCC) continues to increase worldwide, particularly in Western countries. In almost all cases, HCC develops in subjects with hepatic cirrhosis, often as the result of hepatitis B or C virus infection, alcohol abuse or metabolic forms secondary to non-alcoholic steatohepatitis. Patients with HCC and hepatic symptoms can therefore present symptoms that are attributable to both conditions. These patients require multidisciplinary management, calling for close interaction between the hepatologist and the oncologist. Indeed, the treatment of HCC requires, depending on the disease stage and the degree of hepatic impairment, locoregional therapies that can in turn be broken down into surgical and nonsurgical treatments and systemic treatments used in the event of progression after the administration of locoregional treatments. The past decade has seen the publication of countless papers of great interest that have radically changed the scenario of treatment for HCC. Novel therapies with biological agents and immunotherapy have come to be standard options in the approach to treatment of this cancer, obtaining very promising results where in the past chemotherapy was almost never able to have an impact on the course of the disease. However, in addition to being costly, these drugs are not devoid of adverse effects and their management cannot forgo the consideration of the underlying hepatic impairment. Patients with HCC and cirrhosis therefore require special attention, starting from the initial characterisation needed for an appropriate selection of those to be referred for treatment, as these patients are almost never fit. In this chapter, we will attempt to investigate and clarify the key points of the management of the main toxicities induced by locoregional and systemic treatments for HCC secondary to cirrhosis.
Dyshomeostatic modulation of Ca2+-activated K+ channels in a human neuronal model of KCNQ2 encephalopathy

Mutations in KCNQ2, which encodes a pore-forming K+ channel subunit responsible for neuronal M-current, cause neonatal epileptic encephalopathy, a complex disorder presenting with severe early-onset seizures and impaired neurodevelopment. The condition is exceptionally difficult to treat, partially because the effects of KCNQ2 mutations on the development and function of human neurons are unknown. Here, we used induced pluripotent stem cells (iPSCs) and gene editing to establish a disease model and measured the functional properties of differentiated excitatory neurons. We find that patient iPSC-derived neurons exhibit faster action potential repolarization, larger post-burst afterhyperpolarization and a functional enhancement of Ca2+-activated K+ channels. These properties, which can be recapitulated by chronic inhibition of M-current in control neurons, facilitate a burst-suppression firing pattern that is reminiscent of the interictal electroencephalography pattern in patients. Our findings suggest that dyshomeostatic mechanisms compound KCNQ2 loss-of-function leading to alterations in the neurodevelopmental trajectory of patient iPSC-derived neurons.
Effect of vitamin D3 supplementation on hepatic lipid dysregulation associated with autophagy regulatory AMPK/Akt-mTOR signaling in type 2 diabetic mice

Vitamin D3 has been reported to protect liver against non-alcoholic fatty liver disease (NAFLD) by attenuating hepatic lipid dysregulation in type 2 diabetes mellitus (T2DM). However, the mechanism of vitamin D3 on hepatic lipid metabolism-associated autophagy in hyperglycemia-induced NAFLD remains yet to be exactly elucidated. C57BL/6J mice were intraperitoneally injected with 30 mg/kg of streptozotocin and fed a high-fat diet for induction of diabetes. All mice were administered with vehicle or vitamin D3 (300 ng/kg or 600 ng/kg) by oral gavage for 12 weeks. Histological demonstrations of the hepatic tissues were obtained by H&E staining and the protein levels related to lipid metabolism and autophagy signaling were analyzed by Western blot. Treatment with vitamin D3 improved insulin resistance, liver damage, and plasma lipid profiles, and decreased hepatic lipid content in the diabetic mice. Moreover, vitamin D3 administration ameliorated hepatic lipid dysregulation by downregulating lipogenesis and upregulating lipid oxidation under diabetic condition. Importantly, vitamin D3 treatment induced autophagy by activating AMP-activated protein kinase (AMPK), inactivating Akt and ultimately blocking mammalian target of rapamycin (mTOR) activation in the T2DM mice. Additionally, vitamin D3 was found to be effective in anti-apoptosis and anti-fibrosis in the liver of diabetic mice. The results suggested that vitamin D3 may ameliorate hepatic lipid dysregulation by activating autophagy regulatory AMPK/Akt-mTOR signaling in T2DM, providing insights into its beneficial effects on NAFLD in type 2 diabetic patients.
Block Copolymer-Based Magnetic Mixed Matrix Membranes—Effect of Magnetic Field on Protein Permeation and Membrane Fouling

In this study, we report the impact of the magnetic field on protein permeability through magnetic-responsive, block copolymer, nanocomposite membranes with hydrophilic and hydrophobic characters. The hydrophilic nanocomposite membranes were composed of spherical polymeric nanoparticles (NPs) synthesized through polymerization-induced self-assembly (PISA) with iron oxide NPs coated with quaternized poly(2-dimethylamino)ethyl methacrylate. The hydrophobic nanocomposite membranes were prepared via nonsolvent-induced phase separation (NIPS) containing poly (methacrylic acid) and meso-2,3-dimercaptosuccinic acid-coated superparamagnetic nanoparticles (SPNPs). The permeation experiments were carried out using bovine serum albumin (BSA) as the model solute, in the absence of the magnetic field and under permanent and cyclic magnetic field conditions OFF/ON (strategy 1) and ON/OFF (strategy 2). It was observed that the magnetic field led to a lower reduction in the permeate fluxes of magnetic-responsive membranes during BSA permeation, regardless of the magnetic field strategy used, than that obtained in the absence of the magnetic field. Nevertheless, a comparative analysis of the effect caused by the two cyclic magnetic field strategies showed that strategy 2 allowed for a lower reduction of the original permeate fluxes during BSA permeation and higher protein sieving coefficients. Overall, these novel magneto-responsive block copolymer nanocomposite membranes proved to be competent in mitigating biofouling phenomena in bioseparation processes.
Development of directed and random exploration in children.

Are young children just random explorers who learn serendipitously? Or are even young children guided by uncertainty-directed sampling, seeking to explore in a systematic fashion? We study how children between the ages of 4 and 9 search in an explore-exploit task with spatially-correlated rewards, where exhaustive exploration is infeasible and not all options can be experienced. By combining behavioral data with a computational model that decomposes search into similarity-based generalization, uncertainty-directed exploration, and random exploration, we map out developmental trajectories of generalization and exploration. The behavioral data show strong developmental differences in children's capability to exploit environmental structure, with performance and adaptiveness of sampling decisions increasing with age. Through model-based analyses, we disentangle different forms of exploration, finding signatures of both uncertainty-directed and random exploration. The amount of random exploration strongly decreases as children get older, supporting the notion of a developmental "cooling off" process that modulates the randomness in sampling. However, even at the youngest age range, children do not solely rely on random exploration. Even as random exploration begins to taper off, children are actively seeking out options with high uncertainty in a goal-directed fashion, and using inductive inferences to generalize their experience to novel options. Our findings provide critical insights into the behavioral and computational principles underlying the developmental trajectory of learning and exploration.
Study on Preparation of Acylated Soy Protein and Stability of Emulsion.

BACKGROUND Protein can be used as an emulsifier to improve emulsion stability at the interface of water-in-oil emulsion. However, natural soybean protein isolate (SPI) does not meet the high demands as an emulsifier in the food industry. The effect of acylation modification by ethylenediaminetetraacetic dianhydride (0-300 g kg-1 ) on the physicochemical properties of SPI was studied. RESULTS The results of the FTIR spectra analyses showed that carboxyl groups were introduced into the SPI structure by the EDTAD treatment. The carboxyl concentration of SPI was increased by 30 % to 74.07 % with the increase of EDTAD addition from 50 to 300 g kg-1 . When 150 g kg-1 EDTAD was added, the surface Hydrophobicity, the emulsifying activity and the absolute value of the zeta potential were increased by 213 %, 120 % and 68% respectively, while the particle size decreased to 247 nm. The droplet size of emulsion decreased to 10μm when pH was 6. At the same concentration of SPI and pH, the absolute value of zeta potential of the emulsion was biggest. A comparison of the emulsions during storage showed the improvement of emulsion stability related to the increase in the zeta potential and the decrease in the average particle size. The experimental group showed no destabilization on the 21st day and no obvious aggregation phenomenon was observed. CONCLUSION The acylation modification by EDTAD changed the emulsifying properties of SPI and enhanced the stability of SPI emulsion. This article is protected by copyright. All rights reserved.
Abstract to publication conversion in pediatric critical care medicine in Pakistan

Background To determine the rate of conversion of abstracts presented at conferences into full-text articles published in peer-reviewed journals in the field of pediatric critical care medicine (PCCM) in a developing country. Methods We retrospectively reviewed PCCM abstracts from Pakistan presented at national and international pediatric and critical care conferences over 10 years (January 2010 to March 2020). Data included abstract characteristics, such as presentation (poster/oral), presenter (fellow/resident), time of meeting (month and year), type of meeting, study design and topic; and publication characteristics, such as journal name, time (month and year) and first author. The primary outcome was publication rate of PCCM abstracts presented in meetings and time (months) from presentation to publication. Results A total of 79 PCCM abstracts were presented in 20 meetings during the study period. There were 65 poster presentations (82.28%), of which 63 (79.74%) were presented at international critical care conferences and all presenters were PCCM fellows. In total, 64 (81%) abstracts were descriptive observational studies (retrospective: 50, 63.29%) and prospective (14, 17.72%). Only one was an interventional randomized controlled trial. The publication rate of PCCM abstracts was 63.3% (50/79) and the mean time to publication was 12.39±13.61 months. The publication rate was significantly correlated to the year of publication (P<0.001). Conclusions The PCCM abstract publication rate and mean time from presentation to publication was 63.3% and 12.39±13.61 months, respectively, in a developing country.
Initiatives to Support Older Women Who Experience Intimate Partner Violence

To contribute to our knowledge about initiatives to support older women who experience intimate partner violence (IPV), we conducted an internet search, online surveys, and telephone interviews with administrators of programs for women who have experienced IPV. We compiled information on initiatives providing individual in-person and telephone support, educational and/or therapeutic groups, and short- and long-term shelters and housing. The interviews provided insights about the history and rationale for these initiatives, strengths, positive outcomes, challenges, and future program development. Our study results can inform the creation of appropriate services to meet the needs of older women who experience IPV.
Lung ultrasound as a prognostic tool in emergency patients clinically suspected of COVID-19.

INTRODUCTION Tools to quickly triage and evaluate patients with suspected COVID-19 in an emergency department (ED) can improve patient care and reduce risk of overcrowding. The aim of this study was to evaluate if lung ultrasound (LUS) may provide valuable prognostic information in adult patients suspected of COVID-19. METHODS A prospective cohort study of adult patients in an ED was conducted. LUS was performed within one hour of the patients' arrival; COVID-19 was defined by a respiratory syndrome coronavirus 2 RNA positive test. The primary outcome was the proportion of patients suspected of COVID-19 and normal LUS with critical outcomes during follow-up, defined as one or more of the following: need of non-invasive ventilation (NIV), invasive mechanical ventilation, intensive care unit (ICU) stay or death. Follow-up was 14 days. RESULTS A total of 83 patients were included between 9 March and 12 April 2020. In all, 47 (57%; 95% confidence interval (CI): 45.3-67.5%) had a normal LUS, 46 (98%; 95% CI: 88.7-99.9%) of whom had no critical outcomes. A total of 36 (43%; 95% CI: 32.5-54.7%) had an abnormal LUS, eight of whom (22%; 95% CI: 10.1-39.2%) had critical outcomes. Nine (11%; 95%: CI 5.1-19.6%) had one or more critical outcomes: three on NIV, five in ICUs, four on invasive mechanical ventilation and two died. Among the 12 patients (14%; 95% CI: 7.7-23.9%) tested positive for COVID-19, 11 (92%; 95% CI: 61.5-99.8%) had an abnormal LUS. CONCLUSIONS Among adult ED patients suspected of COVID-19, a normal LUS is associated with a low risk of critical outcomes. LUS might be considered for routine use as a prognostic tool in patients suspected of COVID-19. FUNDING none. TRIAL REGISTRATION not relevant.
Aesthetic and functional outcomes of thinned anterolateral thigh flap in reconstruction of complex wounds of the upper limb

We studied outcomes of reconstruction of complex upper limb wounds using thinned anterolateral thigh flaps. There were 18 patients with a mean age of 27.5 years. The mean thickness of the flap before and after thinning was 23 mm and 5 mm, respectively. Two patients had partial tip necrosis that was treated conservatively. Aesthetic and functional evaluations were performed using a 5-point Likert scale, QuickDASH score, passive range of motion and power grip at 12 months after surgery. The study showed good results in the aesthetic evaluation by a panel of plastic surgeons (mean score: 19.7) and patient self-assessment (mean score: 18.1). There was a significant correlation between the total scores of the panel and the patients. The mean QuickDASH score was 21, with a high percentage in the middle category ‘had a problem but working’. The thinned anterolateral thigh flap is versatile and safe in upper limb reconstruction with good aesthetic and functional results. Level of evidence: IV
Textural, Water Holding, and Sensory Properties of Low-fat Pork Bologna with Normal or Waxy Starch Hull-less Barley

All ultra-low-fat (< 1%) pork bolognas had similar cook yield and composition. Addition of 4% hull-less waxy barley flour or meal to formulations provided the greatest purge control; 4% normal starch barley, wheat flour and potato starch were intermediate; 0.25% kappa-carrageenan or 1% soy protein concentrate had little effect on water holding and texture. Expressible moisture and purge were significantly correlated to moisture content and batter viscosity. Formulations with wheat flour and waxy barley meal were scored the firmest, while bologna with potato starch required the most force to compress. For most sensory properties, barley fractions performed similarly
Experiences of veterans with spinal cord injury related to annual urine screening and antibiotic use for urinary tract infections

Antimicrobial‐resistant bacterial infections are an increasing public health threat and people with spinal cord injury (SCI) are disproportionally at higher risk. National guidelines concerning urine testing after SCI are conflicting. Unnecessary urine testing in the SCI population (with high asymptomatic bacteriuria prevalence) leads to unnecessary antimicrobial use, propagating resistant infections, especially urinary tract infections (UTIs).
Liquid crystal oligomers: going beyond dimers

This review focuses on structure-property relationships in liquid crystal oligomers, which consist of molecules containing two or more mesogenic units linked via flexible spacers essentially in a linear fashion and so does not consider, for example, liquid crystal dendrimers and tetrapodes. Previous reviews have tended to focus mainly on liquid crystal dimers in which just two mesogenic units are interconnected by a single spacer. By contrast, this review is largely devoted to higher oligomers such as liquid crystal trimers and tetramers containing three or four mesogenic units connected by two or three spacers, respectively.
Partial remission of Type 2 diabetes and changes in quality of life after gastric bypass.

INTRODUCTION The prevalence of severe obesity is increasing and highly associated with co-morbidities such as Type 2 diabetes (T2D). Furthermore, quality of life (QoL) is negatively affected among patients with severe obesity and T2D. Studies have found that gastric bypass surgery may lead to remission of T2D and improved QoL. The aim of this study was to investigate the association between partial remission of T2D and change in QoL from baseline to a one-year follow-up in severely obese patients undergoing laparoscopic Roux-en-Y gastric bypass (LRYGB). METHODS This cohort study was based on data from patients with T2D undergoing LRYGB at a private hospital in Denmark and included 704 patients among whom 337 (48%) patients with T2D contributed with data in the analysis. Data were collected preoperatively and at a one-year follow-up. Preoperative T2D status was patient-reported and validated through the patient's medical record. At the one-year follow-up, partial remission was defined as an HbA1c concentration less than 7.3% with no use of antidiabetics. Continued T2D was defined as intake of diabetic medication or an HbA1c concentration > 7.3%. QoL was measured by the Moorehead-Ardelt QoL Questionnaire. Multiple linear regression was applied. RESULTS At the one-year follow-up, the prevalence of partial remission of T2D was 72.7%. No significant association was seen between partial remission of T2D after LRYGB and change in QoL one year later. Loss to follow-up was 35.8%. CONCLUSIONS The majority of patients with T2D experienced partial remission one year after undergoing LRYGB surgery. However, partial remission of T2D was not associated with an improved QoL. FUNDING none. TRIAL REGISTRATION not relevant.
Allelic composition of carotenoid metabolic genes in 13 founders influences carotenoid composition in juice sac tissues of fruits among Japanese citrus breeding population

To enrich carotenoids, especially β-cryptoxanthin, in juice sac tissues of fruits via molecular breeding in citrus, allele mining was utilized to dissect allelic variation of carotenoid metabolic genes and identify an optimum allele on the target loci characterized by expression quantitative trait (eQTL) analysis. SNPs of target carotenoid metabolic genes in 13 founders of the Japanese citrus breeding population were explored using the SureSelect target enrichment method. An independent allele was determined based on the presence or absence of reliable SNPs, using trio analysis to confirm inheritability between parent and offspring. Among the 13 founders, there were 7 PSY alleles, 7 HYb alleles, 11 ZEP alleles, 5 NCED alleles, and 4 alleles for the eQTL that control the transcription levels of PDS and ZDS among the ancestral species, indicating that some founders acquired those alleles from them. The carotenoid composition data of 263 breeding pedigrees in juice sac tissues revealed that the phenotypic variance of carotenoid composition was similar to that in the 13 founders, whereas the mean of total carotenoid content increased. This increase in total carotenoid content correlated with the increase in either or both β-cryptoxanthin and violaxanthin in juice sac tissues. Bayesian statistical analysis between allelic composition of target genes and carotenoid composition in 263 breeding pedigrees indicated that PSY-a and ZEP-e alleles at PSY and ZEP loci had strong positive effects on increasing the total carotenoid content, including β-cryptoxanthin and violaxanthin, in juice sac tissues. Moreover, the pyramiding of these alleles also increased the β-cryptoxanthin content. Interestingly, the offset interaction between the alleles with increasing and decreasing effects on carotenoid content and the epistatic interaction among carotenoid metabolic genes were observed and these interactions complexed carotenoid profiles in breeding population. These results revealed that allele composition would highly influence the carotenoid composition in citrus fruits. The allelic genotype information for the examined carotenoid metabolic genes in major citrus varieties and the trio-tagged SNPs to discriminate the optimum alleles (PSY-a and ZEP-e) from the rest would promise citrus breeders carotenoid enrichment in fruit via molecular breeding.