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We explored glucometabolic and renal function after engraftment in all 159 consecutive patients with type 1 diabetes who received pancreas transplantation alone (PTA, n = 80) or simultaneous pancreas and kidney transplantation (SPK, n = 79) in Norway from 2012 until 2017. We report fasting levels of plasma glucose (FPG), C-peptide, eGFR and the homeostasis model assessment of insulin sensitivity (HOMA2(%S)) and beta-cell function (HOMA2(%B)) measured one to three times weekly during the first 8 and at 52 weeks after transplantation. One year after engraftment, in the PTA and SPK groups 52 and 64 were normoglycaemic without exogenous insulin, and two and zero patients were dead. Data at the 52-week visit were missing for 5 and 6 patients in the respective groups. During the first 8 weeks, FPG was lower, C-peptide and HOMA2(%S) were higher and eGFR was lower in the SPK group as compared with the PTA group (all p  less then  .05). 30 out of 157 living patients needed insulin treatment 52 weeks after transplantation, 9/79 in the SPK group and 21/78 in the PTA group (p = .02). In conclusion, patients who underwent SPK showed lower insulin sensitivity, but higher insulin secretory capacity and lower mean blood glucose levels the first 8 weeks after transplantation. Also, a higher proportion of patients in the SPK group were insulin-free after 1 year, compared with the PTA group.Introduction Precision medicine is the concept of treating diseases based on environmental factors, lifestyles, and molecular profiles of patients. This approach has been found to increase success rates of clinical trials and accelerate drug approvals. However, current precision medicine applications in early drug discovery use only a handful of molecular biomarkers to make decisions, whilst clinics gear up to capture the full molecular landscape of patients in the near future. Ipatasertib inhibitor This deep multi-omics characterization demands new analysis strategies to identify appropriate treatment regimens, which we envision will be pioneered by artificial intelligence.Areas covered In this review, the authors discuss the current state of drug discovery in precision medicine and present our vision of how artificial intelligence will impact biomarker discovery and drug design.Expert opinion Precision medicine is expected to revolutionize modern medicine; however, its traditional form is focusing on a few biomarkers, thus not equipped to leverage the full power of molecular landscapes. For learning how the development of drugs can be tailored to the heterogeneity of patients across their molecular profiles, artificial intelligence algorithms are the next frontier in precision medicine and will enable a fully personalized approach in drug design, and thus ultimately impacting clinical practice.Objective The Boston Cognitive Assessment (BoCA) is a novel, computerized, self-administered assessment of global cognition. This work sought to establish the validity and reliability of the BoCA. Method Two studies were conducted. The first study used a sample of 43 outpatients from a clinic in eastern Massachusetts to evaluate the content validity and internal consistency of the BoCA. The second study used a sample of 38 patients seen at an outpatient specialty neurological clinic to evaluate the BoCA's test-retest reliability after one week. Results In the first study, participants without cognitive diagnoses scored significantly higher on both the BoCA and the Telephone Interview for Cognitive Status (TICS) compared to those with mild Neurocognitive Disorders. Correlational analyses revealed moderate correlations between several of the BoCA tasks and measures of related abilities. Exploratory factor analysis of the BoCA tasks revealed one robust factor accounting for a plurality (i.e., 42%) of variance in participant scores. The BoCA demonstrated good internal consistency (α = 0.79) and strong correlations (r = 0.80, p  less then  0.01) with the TICS. The second study revealed strong (r = 0.89, p  less then  0.001) test-retest reliability of the total BoCA score one week after participants' initial administration. Conclusions This work provides evidence of the BoCA's psychometric properties as a self-administered screener of global cognition, and supports its implementation in clinical practice and future studies. Clinical implications, future directions, and limitations are discussed.It is well known that poly(2-methoxyethyl acrylate) (PMEA) has good blood compatibility and its performance is attributed to its water structure. Recently, we applied solution nuclear magnetic resonance spectroscopy (solution-NMR) for analyzing the water structure in PMEA at ambient temperature and concluded that this method is useful because of the clear observation of the resonance peaks at low and high magnetic field (downfield and upfield, respectively) areas indicating the existence of more than two types of water. The present study was performed to compare the water structure of poly(tetrahydrofurfuryl acrylate) (PTHFA) and poly(2-hydroxyethyl methacrylate) (PHEMA) using solution 2H-NMR and deuterium oxide as water at the temperature range 15-45 °C. It was found that PTHFA has a different water structure from that of PHEMA. Water in PTHFA clearly showed two resonance peaks at downfield and upfield areas, with different spin-lattice relaxation times, T12H (high and low values, respectively). These observations are similar to those of PMEA. In contrast, PHEMA showed only one broad resonance peak (at downfield) with a low T12H value. Based on these observations, this study discusses the effect of water structures on the blood compatibility of these polymers.Introduction The outcome of chronic myeloid leukemia (CML) patients in chronic phase has changed after the introduction of tyrosine kinase inhibitors (TKIs). The life expectancy is actually similar to that of the general population. Prognostic stratification at baseline is part of a patient-centered approach to decide the best therapeutic approach.Areas covered In this review, the current prognostic factors examined at baseline are detailed and the meaning is explained. A broad research on Medline, Embase and archives from EHA and ASH congresses, was performed. Prognostic factors have been divided into patient-related (age, gender, comorbidities, etc.) and disease-related (additional cytogenetic abnormalities, type of transcript, etc). New information about genomic data and the potential role of patient-reported outcomes is also discussed.Expert Opinion Prognostic factors at baseline should be considered to evaluate the long-term probability of disease-related death, the possible toxicity, and the projected long-term overall survival. The genomic assessment would provide the basis for a genomic-based risk and help in oriented decision-making process.Eribulin inhibits microtubule polymerization and suppresses epithelial-mesenchymal transition. Conventional pathology approaches have not identified a precise predictive biomarker for Eribulin. We performed qmIF on pre-treatment tissue from 11 patients (6 TNBC, 5 HGSOC) treated with Eribulin-LF. T-lymphocytes were the dominant immune-subset in TME, with higher levels detected in stroma vs tumor (9% vs 2%). Greater density of CD3+ (p = 0.01) and CD3 + CD8+ (p = 0.03) cells and closer proximity between CD3 + CD8+ and tumor cells was observed in the patients with disease control (PR + SD) vs. progressive disease. QmIF identified an association between TIL infiltration and Eribulin-LF sensitivity, which should be evaluated further in prospective studies.The purpose of this study was to develop a novel drug-polymer conjugation (mPEG-b-PCL-DOX) and study on its toxicity, bio-safety, and in vitro antitumor activity of mPEG-b-PCL-DOX. The polymer methoxy poly(ethylene glycol)-block-poly(ε-caprolactone) (mPEG-b-PCL) was prepared by ring-opening polymerization. Then, succinic anhydride was reacted with mPEG-b-PCL via esterification reaction to produce mPEG-b-PCL-COOH. Finally, the polymer mPEG-b-PCL-DOX was obtained by conjugating DOX to mPEG-b-PCL-COOH by amidation. The Fourier transform infrared spectroscopy (FTIR) and 1H nuclear magnetic resonance (1H NMR) spectra were used to study the structures of obtained polymers. Transmission electron microscope (TEM) and Dynamic laser scattering (DLS) were employed to monitor the morphology and size distribution of mPEG-b-PCL-DOX nanoparticles (NPs). The mPEG-b-PCL-DOX NPs were administrated to KM rats by intraperitoneal injection to study the bio-safety of final NPs. The cell uptake and in vitro anti-tumor activity of final NPs were carried out with HCT116 cells as models. FTIR and 1H NMR spectra confirmed the obtaining of mPEG-b-PCL-DOX. The fabricated NPs were in round shapes with an average diameter of 300 nm. These NPs did not induce hemolysis and physiological or pathological changes in rats's organs. Finally, cell teats showed that these NPs could be endocytosed by HCT 116 cells, and they had better anti-tumor effects than free DOX did. Therefore, the mPEG-b-PCL-DOX NPs had a potential application in anti-cancer therapy.A series of schiartane C29 nortriterpenoids with 5/5/7/6/5 membered consecutive rings (1‒5) with an unique schinortriterpenoid skeleton including a new, kadcoccilactone V (1), together with four known ones (2‒5) and three known triterpenoids (6‒8) were identified from stems of Kadsura coccinea (Lem.) A. C. Smith. The structures of 1 and known compounds were elucidated by interpretation of 1D and 2D NMR, and HR-ESI-MS data as well as comparing those data in the literature. All the isolated compounds were examined for cytotoxic effects against six human cancer cell lines [(HCT-15 (colon), NUGC-3 (stomach), NCI-H23 (lung), ACHN (renal), PC-3 (prostate), and MDA-MB-231 (breast)]. Among them, compound 6 showed potent cytotoxicity against NCI-H23 (GI50 1.28 µM) and NUGC-3 (GI50 1.28 µM), and significantly inhibited on PC-3, MDA-MB-231, ACHN, HCT-15 with GI50 values around 2.33 to 2.67 µM.Staphylococcus aureus is considered the most common opportunistic pathogen in humans, capable of forming biofilm, increasing the chances of antibiotic resistance and causes several chronic diseases. Biodiversity is a source of inspiration in the search for new agents against these microorganisms. Hitherto, the efficacy of Hypericum sp. extracts as an antibacterial agent has already been demonstrated against Gram-positive and Gram-negative bacteria. In this study, we observed that until 4 µg/mL, the Hypericum brasiliense extract showed bactericidal activity against a clinical multidrug-resistant S. aureus strain (HU25) and also inhibited biofilm formation at 1/2xMIC (confirmed by SEM) and 1/4xMIC. The extract was also proportionally active against 6 h-preformed biofilm to its concentration (1/2xMIC, 1/4xMIC, p value ≤ 0.05). These promising results make Hypericum brasiliense extract a strong candidate to treat S. aureus infections, including anti-biofilm therapy.The purpose of this study was to determine the relationship between matchday wellness status and a technical-tactical performance construct during rugby match-play. One hundred and thirty-three male rugby union players (73 forwards and 60 backs) from five under-18 national squads who participated in the under-18 Six Nations competition completed a subjective wellness questionnaire on each matchday morning. Players subjectively rated each item (sleep quality, fatigue, muscle soreness, stress and mood) on a five-point Likert scale to calculate their daily wellness status (i.e. difference between matchday and baseline perceived wellness). Technical-tactical performance during match-play was quantified by coding individual key performance indicators (e.g. number of carries, number of tackles). Partial least squares correlation analysis (PLSCA) was employed to compute the latent variables of perceived wellness status (X matrix) and technical-tactical performance (Y matrix) for each player observation (n = 271). The latent variables are a construct of each variable group, enabling higher dimensional data to be visualised more simply.