Miracle-dz/UniFAR-FTUs huggingface dataset:
Hyperthyroidism in Pregnancy and Lactation: A Different Paradigm?

Graves disease (GD) and β-human chorionic gonadotropin (hCG)-mediated hyperthyroidism are the most common causes of hyperthyroidism in pregnancy. Whereas hCGmediated hyperthyroidism is usually transient and benign, thyrotoxicosis due to GD warrants treatment. Fortunately, overt hyperthyroidism affects only 0.1% to 0.4% of pregnancies [1]; when it does occur, it is associated with an increased risk of adverse maternal and fetal outcomes. Before the advent of thionamides, thyroidectomy was the only available treatment for thyrotoxic pregnant women and was accompanied by a high rate of fetal loss. Thionamides were developed between 1947 and 1953, thanks mainly to the pioneering work of Dr Edwin Bennet Astwood. In 1949, Chapman and Corner demonstrated that the fetal thyroid concentrated radioactive iodine (RAI), raising concerns about its use during pregnancy [2]. Since the discovery of thionamides, almost no new oral therapeutic options for GD have emerged. Although propylthiouracil (PTU) and methimazole are both known to have teratogenicity, particularly during the first trimester, these medications are considered safe for use during lactation and approved by the American Academy of Pediatrics. Additionally, thionamides and RAI have been shown to transfer to breast milk. In 1980, Kampmann et al showed that only 0.025% of the administered dose of PTU was excreted in breast milk [3]. In a study of 139 thyrotoxic nursing mothers treated with up to 20 mg of methimazole daily, no deleterious effects on their infants’ thyroid function or development were noted [4]. In a smaller study of 11 infants, there were no adverse effects on the thyroid function of breastfed infants whose mothers were treated with up to 750 mg of PTU daily [5]. According to the 2017 American Thyroid Association (ATA) guidelines, the lowest effective dose of both methimazole and PTU should be used in lactating women, since both medications are detectable in breastmilk. Whereas I is absolutely contraindicated in lactation, the ATA makes allowance for the use of I, if breastmilk is pumped and discarded for 3 to 4 days before breastfeeding is resumed. Iodine-induced hypothyroidism has been reported in infants exposed to high doses of inorganic iodine as reported previously by Hamada et al [6]. This is thought to be mediated by the homeostatic inhibition of thyroid hormone synthesis by decreased iodine uptake by the thyroid gland (Wolff-Chaikoff effect). The present study by Hamada and colleagues [7] prospectively looked at the thyroid function of breastfed infants of women who opted for treatment of their mild GD with potassium iodide (KI). The authors built on their earlier study of 26 such infants in which only one infant
Polymorphism of Interleukin-1 Gene Cluster in Polish Patients with Acute Coronary Syndrome

Background and objectives: Some experimental studies demonstrated adverse modulation of atherothrombosis by interleukin-1beta (IL-1b). To assess the relationship between the five most common variants of three polymorphisms of the IL1b gene cluster and the complexity of coronary atherosclerosis expressed in Gensini Score (GS), and the age of onset of the first acute coronary syndrome (ACS), we assessed the patients (pts) hospitalized due to ACS in this aspect. Materials and Methods: 250 individuals were included. The single nucleotide polymorphisms of IL1b gene: transition T/C at -31 position, C/T at -511, and those of IL1 receptor antagonist gene (IL1RN)—variable number of tandem repeats allele 1, 2, 3, or 4—were determined by PCR. GS was calculated from the coronary angiogram performed at the index ACS. The impact of the presence of T or C and allele 1 to 4 at the investigated loci on the mean GS, GS greater than 40, mean age of onset of ACS, and the fraction of pts over 60 years of age at ACS were compared between the five most common genotype variants. Results: The five most common variants were present in 203 pts (81.2%). Patients with pair 22 in ILRN had the lowest rate and those with pair 12 had the highest rate of ACS before 60 years of age (29.4 vs. 67.8%; p = 0.004). GS > 40 entailed an eight-fold increase of risk, as observed when pts with one T allele at locus -31 were compared with carriers of 2 or no T allele at this locus: OR 8.73 [CI95 4.26–70.99] p = 0.04. Conclusion: Interleukin-1 beta is subject to frequent genetic variability and our results show a potential relationship of this polymorphism with the extent of coronary atherosclerosis and age at the first ACS.
Impact of Heart Failure on In-Hospital Outcomes after Surgical Femoral Neck Fracture Treatment

Background: Femoral neck fracture (FNF) is a common condition with a rising incidence, partly due to aging of the population. It is recommended that FNF should be treated at the earliest opportunity, during daytime hours, including weekends. However, early surgery shortens the available time for preoperative medical examination. Cardiac evaluation is critical for good surgical outcomes as most of these patients are older and frail with other comorbid conditions, such as heart failure. The aim of this study was to determine the impact of heart failure on in-hospital outcomes after surgical femoral neck fracture treatment. Methods: We performed a retrospective study using the Spanish National Hospital Discharge Database, 2007–2015. We included patients older than 64 years treated for reduction and internal fixation of FNF. Demographic characteristics of patients, as well as administrative variables, related to patient’s diseases and procedures performed during the episode were evaluated. Results: A total of 234,159 episodes with FNF reduction and internal fixation were identified from Spanish National Health System hospitals during the study period; 986 (0.42%) episodes were excluded, resulting in a final study population of 233,173 episodes. Mean age was 83.7 (±7) years and 179,949 (77.2%) were women (p < 0.001). In the sample, 13,417 (5.8%) episodes had a main or secondary diagnosis of heart failure (HF) (p < 0.001). HF patients had a mean age of 86.1 (±6.3) years, significantly older than the rest (p < 0.001). All the major complications studied showed a higher incidence in patients with HF (p < 0.001). Unadjusted in-hospital mortality was 4.1%, which was significantly higher in patients with HF (18.2%) compared to those without HF (3.3%) (p < 0.001). The average length of stay (LOS) was 11.9 (±9.1) and was also significantly higher in the group with HF (16.5 ± 13.1 vs. 11.6 ± 8.7; p < 0.001). Conclusions: Patients with HF undergoing FNF surgery have longer length of stay and higher rates of both major complications and mortality than those without HF. Although their average length of stay has decreased in the last few years, their mortality rate has remained unchanged.
Cross-Sectional Association between Hypercholesterolemia and Knee Pain in the Elderly with Radiographic Knee Osteoarthritis: Data from the Korean National Health and Nutritional Examination Survey

Few studies have reported the relationship between knee pain and hypercholesterolemia in the elderly population with osteoarthritis (OA), independent of other variables. The aim of this study was to reveal the association between knee pain and metabolic diseases including hypercholesterolemia using a large-scale cohort. A cross-sectional study was conducted using data from the Korea National Health and the Nutrition Examination Survey (KNHANES-V, VI-1; 2010–2013). Among the subjects aged ≥60 years, 7438 subjects (weighted number estimate = 35,524,307) who replied knee pain item and performed the simple radiographs of knee were enrolled. Using multivariable ordinal logistic regression analysis, variables affecting knee pain were identified, and the odds ratio (OR) was calculated. Of the 35,524,307 subjects, 10,630,836 (29.9%) subjects experienced knee pain. Overall, 20,290,421 subjects (56.3%) had radiographic OA, and 8,119,372 (40.0%) of them complained of knee pain. Multivariable ordinal logistic regression analysis showed that among the metabolic diseases, only hypercholesterolemia was positively correlated with knee pain in the OA group (OR 1.24; 95% Confidence Interval 1.02–1.52, p = 0.033). There were no metabolic diseases correlated with knee pain in the non-OA group. This large-scale study revealed that in the elderly, hypercholesterolemia was positively associated with knee pain independent of body mass index and other metabolic diseases in the OA group, but not in the non-OA group. These results will help in understanding the nature of arthritic pain, and may support the need for exploring the longitudinal associations.
The Inverse Spacer—A Novel, Safe, and Cost-Effective Approach in Routine Procedures for Revision Knee Arthroplasty

Background: A major disadvantage of current spacers for two-stage revision total knee arthroplasty (R-TKA) is the risk of (sub-) luxation during mobilization in the prosthesis-free interval, limiting their clinical success with detrimental consequences for the patient. The present study introduces a novel inverse spacer, which prevents major complications, such as spacer (sub-) luxations and/or fractures of spacer or bone. Methods: The hand-made inverse spacer consisted of convex tibial and concave femoral components of polymethylmethacrylate bone cement and was intra-operatively molded under maximum longitudinal tension in 5° flexion and 5° valgus position. Both components were equipped with a stem for rotational stability. This spacer was implanted during an R-TKA in 110 knees with diagnosed or suspected periprosthetic infection. Postoperative therapy included a straight leg brace and physiotherapist-guided, crutch-supported mobilization with full sole contact. X-rays were taken before and after prosthesis removal and re-implantation. Results: None of the patients experienced (sub-) luxations/fractures of the spacer, periprosthetic fractures, or soft tissue compromise requiring reoperation. All patients were successfully re-implanted after a prosthesis-free interval of 8 weeks, except for three patients requiring an early exchange of the spacer due to persisting infection. In these cases, the prosthetic-free interval was prolonged for one week. Conclusion: The inverse spacer in conjunction with our routine procedure is a safe and cost-effective alternative to other articulating or static spacers, and allows crutch-supported sole contact mobilization without major post-operative complications. Maximum longitudinal intra-operative tension in 5° flexion and 5° valgus position appears crucial for the success of surgery.
Histopathological and Immune Prognostic Factors in Colo-Rectal Liver Metastases

Simple Summary Clinical management of colo-rectal liver metastasis would benefit from a refined stratification of patients in prognostic groups, in order to identify the best therapeutic option. Efforts are ongoing in the definition of parameters associated with clinical behaviors, which could help classifying patients in clinically relevant groups. Here we aimed at discussing the recent advances in this field, and we introduced current and new promising candidates, such as morphological tumor features and immune components, which have been showing significant association with survival. Some of these parameters are slowly reaching the clinic and further efforts are ongoing in the attempt to combine them in multiparametric scores. Abstract Prognostic studies are increasingly providing new tools to stratify colo-rectal liver metastasis patients into clinical subgroups, with remarkable implications in terms of clinical management and therapeutic choice. Here, the strengths and hurdles of current prognostic tools in colo-rectal liver metastasis are discussed. Alongside more classic histopathological parameters, which capture features related to the tumor component, such as tumor invasion, tumor growth pattern and regression score, we will discuss immune mediators, which are starting to be considered important features. Their objective quantification has shown significant results in prognostication studies, with most of the work focused on adaptive immune cells, namely T cells. As for macrophages, they are only starting to be appreciated and we will present recent advances in evaluation of macrophage morphological features. Deeper knowledge acquired by multiparametric analyses is rapidly uncovering the variety of immune players that should be assessed. The future projection is to implement deep-learning histopathological tools and to integrate histopathological and immune metrics in multiparametric scores, with the ultimate objective to achieve a deeper resolution of the tumor features and their relevance for colo-rectal liver metastasis.
Dehydropeptide Supramolecular Hydrogels and Nanostructures as Potential Peptidomimetic Biomedical Materials

Supramolecular peptide hydrogels are gaining increased attention, owing to their potential in a variety of biomedical applications. Their physical properties are similar to those of the extracellular matrix (ECM), which is key to their applications in the cell culture of specialized cells, tissue engineering, skin regeneration, and wound healing. The structure of these hydrogels usually consists of a di- or tripeptide capped on the N-terminus with a hydrophobic aromatic group, such as Fmoc or naphthalene. Although these peptide conjugates can offer advantages over other types of gelators such as cross-linked polymers, they usually possess the limitation of being particularly sensitive to proteolysis by endogenous proteases. One of the strategies reported that can overcome this barrier is to use a peptidomimetic strategy, in which natural amino acids are switched for non-proteinogenic analogues, such as D-amino acids, β-amino acids, or dehydroamino acids. Such peptides usually possess much greater resistance to enzymatic hydrolysis. Peptides containing dehydroamino acids, i.e., dehydropeptides, are particularly interesting, as the presence of the double bond also introduces a conformational restraint to the peptide backbone, resulting in (often predictable) changes to the secondary structure of the peptide. This review focuses on peptide hydrogels and related nanostructures, where α,β-didehydro-α-amino acids have been successfully incorporated into the structure of peptide hydrogelators, and the resulting properties are discussed in terms of their potential biomedical applications. Where appropriate, their properties are compared with those of the corresponding peptide hydrogelator composed of canonical amino acids. In a wider context, we consider the presence of dehydroamino acids in natural compounds and medicinally important compounds as well as their limitations, and we consider some of the synthetic strategies for obtaining dehydropeptides. Finally, we consider the future direction for this research area.
Kinetics of Polymer/Metal-Ion Gelation

Polyacrylamide and partially hydrolyzed polyacrylamide solutions can be crosslinked by tri-valent chromium ions to form stable gels. In this study the kinetics of the gelation reaction are determined from the time dependence of dynamic mechanical measurements using classical network elasticity theory to relate the storage modulus of the gel to the number density of crosslinks. The reaction is second order in chromium ion concentration corroborating previous reports of a bi-molecular chromium ion complex. Gelation studies with anionic and nonionic polyacrylamides in NaCl, KI, and Na/sub 2/SO/sub 4/ solutions show that electrostatic interactions between chain segments alter the rate of reaction. The effects are successfully modeled using electrostatic theories of Odijk and Fixman.
Task-Specific Ionic Liquids with Lactate Anion Applied to Improve ZnO Dispersibility in the Ethylene-Propylene-Diene Elastomer

Task-specific ionic liquids (TSILs) are ionic liquids with structures and, consequently, properties and behaviors designed for particular applications. In this work, task-specific ILs with alkylammonium or benzalkonium cations and carboxyl groups in the form of lactate anions were used to promote the homogeneous dispersion of the curatives in the elastomer matrix. The reaction of carboxyl groups of TSILs with zinc oxide, which acts as a vulcanization activator, was confirmed. This interaction improved the solubility and dispersibility of zinc oxide particles in the ethylene-propylene-diene (EPDM) monomer matrix, which consequently affected the curing characteristics of rubber compounds. Most importantly, TSILs increased the efficiency of vulcanization by shortening the time, lowering the temperature and increasing the enthalpy of this process, while maintaining safe processing of elastomer composites. EPDM vulcanizates containing TSILs with lactate anion were characterized by satisfactory functional properties.
In vivo, ex vivo and in vitro dasatinib activity in chronic lymphocytic leukemia

Dasatinib inhibits the breakpoint cluster region-Abelson murine leukemia 1 (BCR-ABL1) gene along with other kinases known to be overexpressed and abnormally active in patients with chronic lymphocytic leukemia (CLL). The current study used primary leukemic cells obtained from 53 patients with CLL that were treated with dasatinib. A 2,3-bis-(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide (XTT) assay and Annexin V staining was performed to assess the cytotoxic effects of dasatinib treatment. The XTT assay revealed that the median cytotoxicity of dasatinib was 8.30% (range, 0.00–77.89%). Due to high dispersion of dasatinib activity, patients were divided into sensitive (n=27; 50.94%; median cytotoxicity, 22.81%) and resistant groups (n=26; 49.06%; median cytotoxicity, 0.00%). A median cytotoxicity of 8.30% was selected as a cut off value. Using Annexin V staining and flow cytometry on exemplary sensitive and resistant CLL samples, it was revealed that 17.71 and 1.84% of cells were apoptotic, respectively. The current study presented a case of a patient with concomitant occurrence of CLL and chronic myeloid leukemia (CML) with a major molecular response after dasatinib treatment. A simultaneous reduction of circulating CLL cells indicated in vivo anti-CLL activity induced by dasatinib. After an in vitro culture of the patient's mononuclear cells with subsequent dasatinib treatment, a higher percentage of CLL cells undergoing apoptosis was obsevered when compared with untreated samples (38.19 vs. 21.99%, respectively). Similarly, the percentage of CLL apoptotic cells (ΔΨmlow) measured by chloromethyl-X-rosamine was higher after incubation with dasatinib (7.28%) than in the negative control (2.86%). In conclusion, dasatinib induced antileukemic effects against CML and CLL cells. The results of the current study indicated that dasatinib may induce apoptosis ex vivo, in vitro and in vivo in CLL.
Aortic Valve Disease and Associated Complex CAD: The Interventional Approach

Coronary artery disease (CAD) is highly prevalent in patients with severe aortic stenosis (AS). The management of CAD is a central aspect of the work-up of patients undergoing transcatheter aortic valve implantation (TAVI), but few data are available on this field and the best percutaneous coronary intervention (PCI) practice is yet to be determined. A major challenge is the ability to elucidate the severity of bystander coronary stenosis independently of the severity of aortic valve stenosis and subsequent impact on blood flow. The prognostic role of CAD in patients undergoing TAVI is being still debated and the benefits and the best timing of PCI in this context are currently under evaluation. Additionally, PCI in the setting of advanced AS poses some technical challenges, due to the complex anatomy, risk of hemodynamic instability, and the increased risk of bleeding complications. This review aims to provide a comprehensive synthesis of the available literature on myocardial revascularization in patients with severe AS undergoing TAVI. This work can assist the Heart Team in individualizing decisions about myocardial revascularization, taking into account available diagnostic tools as well as the risks and benefits.
Structural changes of silk fibroin membranes induced by immersion in methanol aqueous solutions

Structural changes of native and regenerated silk fibroin membranes were induced by immersion in water-methanol solutions and examined as a function of immersion time and methanol concentration. X-ray diffractometry and infrared spectroscopy data showed that transition from random coil to β-sheet structure occurred favorably when both native and regenerated silk fibroin membranes were immersed in water-methanol solutions, regardless of the different immersion time. Only native silk membrane, treated for 2 min with pure methanol, maintained its original amorphous structure, as demonstrated by differential scanning calorimetric (DSC) curves. The degree of displacement, measured by thermomechanical analysis (TMA), was much greater for regenerated than for native silk fibroin membranes. SDS-PAGE pattern showed that native silk fibroin has a molecular weight of 350, while the regenerated sample is formed by a large number of polypeptides in the range of 200-50 KD. The amount of acidic and basic amino acids decreased slightly in regenerated silk fibroin. Physical properties of silk membranes treated with water-methanol solutions are discussed in terms of membrane structure, treatment conditions, and chemical structure of starting material. © 1994 John Wiley & Sons, Inc.
A Facile One-Pot Approach to the Synthesis of Gd-Eu Based Metal-Organic Frameworks and Applications to Sensing of Fe3+ and Cr2O72− Ions

Gadolinium metal-organic frameworks (Gd-MOFs) and Eu-doped Gd-MOFs have been synthesized through a one-pot green approach using commercially available reagents. The 1,4-benzenedicarboxylic acid (H2-BDC) and 2,6-naphthalenedicarboxylic acid (H2-NDC) were chosen as ditopic organic linkers to build the 3D structure of the network. The Gd-MOFs were characterized using powder X-ray diffraction (XRD), FT-IR spectroscopy, field emission scanning electron microscopy (FE-SEM) and N2 adsorption–desorption analysis. The Gd-MOF structures were attributed comparing the XRD patterns, supported by the FT-IR spectra, with data reported in the literature for Ln-MOFs of similar lanthanide ionic radius. FE-SEM characterization points to the effect of the duration of the synthesis to a more crystalline and organized structure, with grain dimensions increasing upon increasing reaction time. The total surface area of the MOFs has been determined from the application of the Brunauer–Emmett–Teller method. The study allowed us to correlate the processing conditions and ditopic linker dimension to the network surface area. Both Gd-MOF and Eu-doped Gd-MOF have been tested for sensing of the inorganic ions such as Fe3+ and Cr2O72−.