Miracle-dz/UniFAR-FTUs huggingface dataset:
Durable Effects of iGlarLixi Up to 52 Weeks in Type 2 Diabetes: The LixiLan-G Extension Study

OBJECTIVE In the LixiLan-G trial, switching to iGlarLixi, a once-daily titratable fixed-ratio combination of insulin glargine 100 units/mL and the glucagon-like peptide 1 receptor agonist (GLP-1 RA) lixisenatide, improved glucose control in type 2 diabetes uncontrolled with GLP-1 RAs over 26 weeks versus continuing prior GLP-1 RA. A prespecified, 26-week, single-arm extension of LixiLan-G aimed to determine the durability of iGlarLixi efficacy and safety over 52 weeks. RESEARCH DESIGN AND METHODS Participants with type 2 diabetes uncontrolled by GLP-1 RAs (glycated hemoglobin [HbA1c] 7–9% [53–75 mmol/mol]) were initially randomized to switch to iGlarLixi or continue prior GLP-1 RA. Those randomized to iGlarLixi who completed the 26-week primary end point period could continue iGlarLixi open-label treatment over a 26-week extension to assess durability of efficacy and safety. RESULTS Glycemic control achieved with iGlarLixi at week 26 (mean HbA1c 6.7% [50 mmol/mol]) was maintained at week 52 (mean HbA1c 6.7% [50 mmol/mol]; mean ± SD change from baseline at week 52: −1.0 ± 0.9% [11 ± 10 mmol/mol]). Proportions of participants reaching HbA1c <7% (53 mmol/mol) with iGlarLixi were similar at week 26 (62%) and 52 (64%), as were those reaching this target without documented symptomatic (<3.0 mmol/L) hypoglycemia (57% and 58%). Safety of iGlarLixi was similar at weeks 26 and 52, with low rates of documented symptomatic hypoglycemia and gastrointestinal events. CONCLUSIONS The efficacy and safety of iGlarLixi at the end of the 26-week randomized treatment period was maintained over the 26-week extension period in the LixiLan-G trial.
Value of the urea/creatinine index in isolated urine to estimate severe protein hypercatabolism in ventilated patients

Objective To study the ability of the urea/creatinine index to identify severe protein catabolism from the isolated urine of critically ventilated patients. Methods This was a prospective, observational study. It included 52 patients without kidney failure. Variables: total urinary nitrogen estimated from the urea in 24-hour urine on the second (T1) and fourth days (T2) and urea/creatinine index in isolated urine before 24-hour urine collection. Results Severe protein hypercatabolism (estimated total urinary nitrogen > 15g) was present in 14 patients (26.9%) at T1 and in 29 (55.7%) at T2. Eighty-four percent of patients had low nutritional risk by the Nutrition Risk in the Critically Ill score. At T1, the Pearson correlation between the estimated total urinary nitrogen and the urea/creatinine index was 0.272 (p = 0.051), and at T2 it was 0.276 (p = 0.048). The urea/creatinine index at T2 had a tendency to better discriminate severe protein hypercatabolism than Acute Physiology and Chronic Health Evaluation II and Nutrition Risk in the Critically Ill (AUC 0.741 versus 0.669 and 0.656, 95%CI: 0.602 - 0.880; 0.519 - 0.818 and 0.506 - 0.806, respectively). The optimal cutoff value of the urea/creatinine index for the diagnosis of severe protein hypercatabolism was 16.15, with a sensitivity of 79.31% (95%CI: 59.74 - 91.29), specificity of 60.87% (95%CI: 38.78 - 79.53), positive predictive value 71.88% (95%CI: 53.02 - 85.60), negative predictive value 70.0% (95%CI: 45.67 - 87.18), LR (+) 2.03 (95%CI: 1.18 - 3.49), and LR (-) 0.34 (95%CI: 0.16 - 0.74). Conclusion The urea/creatinine index measured on the fourth day has a certain ability to estimate severe protein hypercatabolism (as defined by estimated total urinary nitrogen) but does not replace total urinary nitrogen in critically ventilated patients without kidney failure. Due to its reasonable sensitivity, it could be used as a screen to identify which patients to take a 24-hour urine sample from.
Maternal Folic Acid Deficiency Is Associated to Developing Nasal and Palate Malformations in Mice

Craniofacial development requires extremely fine-tuned developmental coordination of multiple specialized tissues. It has been evidenced that a folate deficiency (vitamin B9), or its synthetic form, folic acid (FA), in maternal diet could trigger multiple craniofacial malformations as oral clefts, tongue, or mandible abnormalities. In this study, a folic acid-deficient (FAD) diet was administered to eight-week-old C57/BL/6J female mouse for 2–16 weeks. The head symmetry, palate and nasal region were studied in 24 control and 260 experimental fetuses. Our results showed a significant reduction in the mean number of fetuses per litter according to maternal weeks on FAD diet (p < 0.01). Fetuses were affected by cleft palate (3.8%) as well as other severe congenital abnormalities, for the first time related to maternal FAD diet, as head asymmetries (4.6%), high arched palate (3.5%), nasal septum malformed (7.3%), nasopharynx duct shape (15%), and cilia and epithelium abnormalities (11.2% and 5.8%). Dysmorphologies of the nasal region were the most frequent, appearing at just four weeks following a maternal FAD diet. This is the first time that nasal region development is experimentally related to this vitamin deficiency. In conclusion, our report offers novel discoveries about the importance of maternal folate intake on midface craniofacial development of the embryos. Moreover, the longer the deficit lasts, the more serious the consequent effects appear to be.
Factors Affecting the Cases and Deaths of COVID-19 Victims

This paper attempts to find the factors that affect the number of cases and deaths of coronavirus disease 2019 (COVID-19) patients a year after the first outbreak in Wuhan, China. There were 141 countries affected with COVID-19 involved in the study. Countries were grouped based on population. Using ordinary least squares regression, it was found that the total number of cases and deaths were significantly related with the levels of population of the different countries. On the overall, median age of the country, and average temperature are positively related with the number of deaths from the virus. On the other hand, population density is positively related with the deaths due to COVID for low populated countries. The result of this preliminary study can be used as a benchmark for authorities in the formulation of policies with regards to treating COVID-19 related issues.
Analysis of health claims regarding creatine monohydrate present in commercial communications for a sample of European sports foods supplements

Abstract Objective: To analyse the information on health claims present in the labelling of creatine monohydrate (CM) products. Design: A descriptive study of a selection of products marketed as CM, with health claims, and that met the inclusion/exclusion criteria, was conducted using the Amazon and Google Shopping websites. The adequacy and compliance of the health claims were evaluated with the European legislative requirements (European Food Safety Authority and European Commission). The results were discussed with scientific evidence criteria from the Academy of Nutrition and Dietetics, International Olympic Committee, and International Society of Sports Nutrition, as well as the systematic review carried out by Mielgo-Ayuso in 2019. Setting: Health claims in the commercial communications of a sample of CM supplements, in relation to current legislation and scientific knowledge. Participant: A total of 554 CM products were obtained. Results: Of the total sample, only 167 met the inclusion/exclusion criteria. Of these, 30·5 % recommended a CM dose of 5·0–5·9 g/d, while 29·9 % recommended 3·0 to 3·9 g/d. As for the health claims, ‘Enhances physical performance’ appeared in 73·1 % of the supplements, in most cases referring to a dosage of 3·0 to 3·9 g/d for these products. The rest of the declarations were not adequate or needed to be modified. Conclusion: Only 25 % of the health claims complied with the criteria established by the scientific reference documents. Most of the declarations must be modified or eliminated, as they could be considered fraudulent and/or misleading for the consumer.
Efficacy of Feed-Based Formalin-Killed Vaccine of Streptococcus iniae Stimulates the Gut-Associated Lymphoid Tissues and Immune Response of Red Hybrid Tilapia

Red hybrid tilapia were fed a formalin-killed oral Streptococcus iniae vaccine (FKV) in the present study was assessed. Three hundred Red hybrid tilapia 80 ± 10 g were divided into five groups (1A, 1B, 2A, 2B, and Cx), each consisting of 60 fish. Fish from Groups 1A, 1B, 2A, and 2B were fed with FKV over different periods of administration, while Group 2B was the only group of fish to receive an oral booster vaccination on day 14- and 21-days post-vaccination (dpv). Group Cx was fed with normal pellets containing no vaccine as a control group. At four weeks post-vaccination (wpv), all fish were experimentally infected with S. iniae. Groups 2A and 2B had the lowest level of mortalities following vaccination (45% and 30%, respectively) compared to Groups 1A and 1B (80% and 55%, respectively), while the level of mortalities in Group Cx was 100%. All vaccinated groups showed a significant increase in anti-S. iniae IgM levels (p < 0.05) in serum, mucus, and gut-lavage, while Group Cx did not (p > 0.05) and all fish in this group died by five weeks post-infection. In conclusion, fish fed with the S. iniae FKV had a greater level of protection against S. iniae, with increased specific antibody response to the vaccine and there was also evidence of GALT stimulation by the vaccine.
The protective effect of Kombucha against silver nanoparticles‐induced toxicity on testicular tissue in NMRI mice

Silver nanoparticles (SNPs) can pass from the cell membrane and testicular blood barrier due to their small size, and by increasing oxidative stress they cause disorder in the male reproductive system. Kombucha is a traditional fermented drink with detoxification and potent antioxidant properties. We aimed to examine the protective effect of Kombucha against the damages due to SNPs on the testis tissue. In this experimental study, NMRI mice were randomly separated into four groups (n = 6), namely control (distilled water), SNPs (500 mg/kg), Kombucha extract (9 ml/kg) and SNPs + Kombucha, and were treated with gavage for 35 days. A significant decrease in testosterone level and total antioxidant capacity, and a significant increase in malondialdehyde concentration was observed in the SNPs group in comparison with the control group. Histological studies on the testis of mice treated with SNPs showed vacuolation, decrease in generational epithelium thickness, seminiferous tubules diameter, testis volume and the number of spermatozoa in lumen of the seminiferous tubule and increase in the volume of interstitial space while the mentioned parameters were improved in the SNPs + Kombucha group compared to the SNPs group. Kombucha reduces the adverse effects of SNPs on testis tissue and improves the function of the male reproductive system.
Selection of Fluorescent, Bioluminescent, and Radioactive Tracers to Accurately Reflect Extracellular Vesicle Biodistribution in Vivo

The ability to track extracellular vesicles (EVs) in vivo without influencing their biodistribution is a key requirement for their successful development as drug delivery vehicles and therapeutic agents. Here, we evaluated the effect of five different optical and nuclear tracers on the in vivo biodistribution of EVs. Expi293F EVs were labeled using either a noncovalent fluorescent dye DiR, or covalent modification with 111indium-DTPA, or bioengineered with fluorescent (mCherry) or bioluminescent (Firefly and NanoLuc luciferase) proteins fused to the EV marker, CD63. To focus specifically on the effect of the tracer, we compared EVs derived from the same cell source and administered systemically by the same route and at equal dose into tumor-bearing BALB/c mice. 111Indium and DiR were the most sensitive tracers for in vivo imaging of EVs, providing the most accurate quantification of vesicle biodistribution by ex vivo imaging of organs and analysis of tissue lysates. Specifically, NanoLuc fused to CD63 altered EV distribution, resulting in high accumulation in the lungs, demonstrating that genetic modification of EVs for tracking purposes may compromise their physiological biodistribution. Blood kinetic analysis revealed that EVs are rapidly cleared from the circulation with a half-life below 10 min. Our study demonstrates that radioactivity is the most accurate EV tracking approach for a complete quantitative biodistribution study including pharmacokinetic profiling. In conclusion, we provide a comprehensive comparison of fluorescent, bioluminescent, and radioactivity approaches, including dual labeling of EVs, to enable accurate spatiotemporal resolution of EV trafficking in mice, an essential step in developing EV therapeutics.
Cow's milk allergy in infancy and later development of type 1 diabetes–nationwide case‐cohort study

It is suggested that early intake of cow's milk could be a risk factor for type 1 diabetes (T1DM). Further, the different immunological background, gives a suggestion of an inverse relationship for the occurrence of these diseases. The aim of this study was to explore the association between cow's milk allergy (CMA) and the risk of T1DM in a register‐based case‐cohort study.
Water‐Soluble Poly(N‐isopropylacrylamide)–Graphene Sheets Synthesized via Click Chemistry for Drug Delivery

Covalently functionalized graphene sheets are prepared by grafting a well‐defined thermo‐responsive poly(N‐isopropylacrylamide) (PNIPAM) via click chemistry. The PNIPAM‐grafted graphene sheets (PNIPAM‐GS) consist of about 50% polymer, which endows the sheets with a good solubility and stability in physiological solutions. The PNIPAM‐GS exhibits a hydrophilic to hydrophobic phase transition at 33 °C, which is relatively lower than that of a PNIPAM homopolymer because of the interaction between graphene sheets and grafted PNIPAM. Moreover, through π–π stacking and hydrophobic interaction between PNIPAM‐GS and an aromatic drug, the PNIPAM‐GS is able to load a water‐insoluble anticancer drug, camptothecin (CPT), with a superior loading capacity of 15.6 wt‐% (0.185 g CPT per g PNIPAM‐GS). The in vitro drug release behavior of the PNIPAM‐GS‐CPT complex is examined both in water and PBS at 37 °C. More importantly, the PNIPAM‐GS does not exhibit a practical toxicity and the PNIPAM‐GS‐CPT complex shows a high potency of killing cancer cells in vitro. The PNIPAM‐GS is demonstrated to be an effective vehicle for anticancer drug delivery.
The Associations between Rapid Strength Development and Muscle Stiffness in Older Population

Background: Previous studies suggest that the capacity for rapid force production of ankle plantar flexors is essential for the prevention of falls in the elderly. In healthy young adults, there were significant associations between rate of force development and muscle stiffness measured by shear wave elastography. However, there has been no study investigating the association of rate of force development with shear elastic modulus in older adults. Methods: The muscle strength and shear elastic modulus of the medial gastrocnemius muscle in both legs were measured in 17 elderly men and 10 elderly women (mean ± SD; 70.7 ± 4.1 years; 160.6 ± 8.0 cm; 58.7 ± 9.5 kg). We investigated the rate of force development of plantar flexors and shear elastic modulus of medial gastrocnemius muscle using by shear wave elastography. Results: Our results showed that there were no significant associations between normalized rate of force development and shear elastic modulus of medial gastrocnemius muscle. Conclusion: This suggests that the capacity of rapid force production could be related not to muscle stiffness of the medial gastrocnemius muscle, but to neuromuscular function in older individuals.
Nanoscale Ferroelectricity in Crystalline γ‐Glycine

Ferroelectrics are multifunctional materials that reversibly change their polarization under an electric field. Recently, the search for new ferroelectrics has focused on organic and bio‐organic materials, where polarization switching is used to record/retrieve information in the form of ferroelectric domains. This progress has opened a new avenue for data storage, molecular recognition, and new self‐assembly routes. Crystalline glycine is the simplest amino acid and is widely used by living organisms to build proteins. Here, it is reported for the first time that γ‐glycine, which has been known to be piezoelectric since 1954, is also a ferroelectric, as evidenced by local electromechanical measurements and by the existence of as‐grown and switchable ferroelectric domains in microcrystals grown from the solution. The experimental results are rationalized by molecular simulations that establish that the polarization vector in γ‐glycine can be switched on the nanoscale level, opening a pathway to novel classes of bioelectronic logic and memory devices.
When Does the Cytokine Storm Begin in COVID-19 Patients? A Quick Score to Recognize It

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the virus that is responsible for coronavirus disease 2019 (COVID-19), which has rapidly spread across the world, becoming a pandemic. The “cytokine storm” (CS) in COVID-19 leads to the worst stage of illness, and its timely control through immunomodulators, corticosteroids, and cytokine antagonists may be the key to reducing mortality. After reviewing published studies, we proposed a Cytokine Storm Score (CSs) to identify patients who were in this hyperinflammation state, and at risk of progression and poorer outcomes. We retrospectively analyzed 31 patients admitted to Infectious Disease Department in “St. Maria” Hospital in Terni with confirmed SARS-CoV-2 infections, and analyzed the “CS score” (CSs) and the severity of COVID-19. Then we conducted a prospective study of COVID-19 patients admitted after the definition of the CSscore. This is the first study that proposes and applies a new score to quickly identify COVID-19 patients who are in a hyperinflammation stage, to rapidly treat them in order to reduce the risk of intubation. CSs can accurately identify COVID-19 patients in the early stages of a CS, to conduct timely, safe, and effect administration of immunomodulators, corticosteroids, and cytokine antagonists, to prevent progression and reduce mortality.
Attachment representations to parents and emotional-behavioral problems: A comparison between children with type 1 diabetes mellitus and healthy children in middle childhood

Type 1 diabetes mellitus (T1D) is one of the most demanding chronic diseases for children and their families, since controlling diabetes involves a process of co-regulation with attachment figures. However, there is insufficient evidence in middle childhood on psychological mechanisms involved that might complicate the adaptation of these children. Therefore, 106 children (N = 31 with T1D and N = 75 as matched healthy group [HG]) aged 8 to 13 were assessed using the Child Attachment Interview, the Child Behavior Checklist, and the measure of glycated hemoglobin. Results showed that insecure T1D children did not have worse diabetes control than the secure ones. However, T1D children differed from HG for higher levels of idealization to father and withdrawn/depressed problems. Moreover, T1D children with insecure attachment to mother scored significantly higher in anxious/depressed, withdrawn/depressed, attention problems, and rule-breaking behavior, while T1D children with insecure attachment to father scored significantly higher only in the withdrawn/depressed scale compared to the remaining children. Therefore, diabetes does not in itself determine a psychological vulnerability in middle childhood, but the presence of an insecure attachment, especially to the mother, worsens the psychological adaptation of T1D children. Psychological support should be provided for these young patients and their families.
Evaluation of retinal and choroidal microvascular changes in patients who received hydroxychloroquine by optical coherence tomography angiography.

PURPOSE The aim of the study is to evaluate the retinal and choroidal microvascular changes via optical coherence tomography angiography in patients who received hydroxy-chloroquine. METHODS In total, 28 eyes of 28 patients (24 females, and 4 males) receiving treatment with hydroxy-chloroquine were assessed in this cross-sectional cohort study (hydroxychloroquine group). The high-and low-risk groups consisted of patients receiving hydroxychloroquine for ≥5 years (14 eyes of 28 patients) and <5 years (14 eyes of 28 patients), respectively. A total of 28 age- and gender-matched volunteers were enrolled as the control group. The macular flow area (superficial, deep, and choriocapillaris), superficial and deep vessel density, foveal avascular zone area, central foveal thickness, and subfoveal choroidal thickness parameters were measured by optical coherence tomography angiography. RESULTS The mean age of the 28 patients who received hydroxychloroquine and the 28 age-matched controls was 45.5 ± 11.1 years (range: 29-70 years) and 44.5 ± 13.9 years (range: 28-70 years), respectively. In patients who received hydroxychloroquine, the values for the superficial, deep, and choriocapillaris macular flow areas were 13.578 ± 0.30, 13.196 ± 0.31, and 17.617 ± 0.42, respectively. In controls, these values were 16.407 ± 0.95, 13.857 ± 0.31, and 18.975 ± 0.76, respectively (p<0.05 for all). The superficial, deep, and cho-riocapillaris flow areas were significantly smaller in patients who received hydroxychloroquine than those in controls (p<0.05 for all). Superficial and deep vessel densities were significantly reduced in patients who received hydroxychlo-roquine in all regions (i.e., foveal, parafoveal, temporal, superior, nasal, and inferior) (p<0.05 for all). Moreover, significant difference was observed between the groups in the foveal avascular zone area (superficial and deep), central foveal thickness, and subfoveal choroidal thickness (p<0.05 for all). CONCLUSIONS Retinochoroidal microvascular flow and vessel density of the macular area were significantly decreased in patients who received hydroxychloroquine. Hy-droxychloroquine may damage the retinochoroidal mi-cro-vascular architecture. Optical coherence tomography angiography may contribute to the early detection of hy-dro-xychloroquine-induced retinal toxicity.
Experienced well-being rises with income, even above $75,000 per year

Significance Past research has found that experienced well-being does not increase above incomes of $75,000/y. This finding has been the focus of substantial attention from researchers and the general public, yet is based on a dataset with a measure of experienced well-being that may or may not be indicative of actual emotional experience (retrospective, dichotomous reports). Here, over one million real-time reports of experienced well-being from a large US sample show evidence that experienced well-being rises linearly with log income, with an equally steep slope above $80,000 as below it. This suggests that higher incomes may still have potential to improve people’s day-to-day well-being, rather than having already reached a plateau for many people in wealthy countries. What is the relationship between money and well-being? Research distinguishes between two forms of well-being: people’s feelings during the moments of life (experienced well-being) and people’s evaluation of their lives when they pause and reflect (evaluative well-being). Drawing on 1,725,994 experience-sampling reports from 33,391 employed US adults, the present results show that both experienced and evaluative well-being increased linearly with log(income), with an equally steep slope for higher earners as for lower earners. There was no evidence for an experienced well-being plateau above $75,000/y, contrary to some influential past research. There was also no evidence of an income threshold at which experienced and evaluative well-being diverged, suggesting that higher incomes are associated with both feeling better day-to-day and being more satisfied with life overall.