Miracle-dz/UniFAR-FTUs huggingface dataset:
A Low Tacrolimus Concentration/Dose Ratio Increases the Risk for the Development of Acute Calcineurin Inhibitor-Induced Nephrotoxicity

Fast tacrolimus metabolism is linked to inferior outcomes such as rejection and lower renal function after kidney transplantation. Renal calcineurin-inhibitor toxicity is a common adverse effect of tacrolimus therapy. The present contribution hypothesized that tacrolimus-induced nephrotoxicity is related to a low concentration/dose (C/D) ratio. We analyzed renal tubular epithelial cell cultures and 55 consecutive kidney transplant biopsy samples with tacrolimus-induced toxicity, the C/D ratio, C0, C2, and C4 Tac levels, pulse wave velocity analyses, and sublingual endothelial glycocalyx dimensions in the selected kidney transplant patients. A low C/D ratio (C/D ratio < 1.05 ng/mL×1/mg) was linked with higher C2 tacrolimus blood concentrations (19.2 ± 8.7 µg/L vs. 12.2 ± 5.2 µg/L respectively; p = 0.001) and higher degrees of nephrotoxicity despite comparable trough levels (6.3 ± 2.4 µg/L vs. 6.6 ± 2.2 µg/L respectively; p = 0.669). However, the tacrolimus metabolism rate did not affect the pulse wave velocity or glycocalyx in patients. In renal tubular epithelial cells exposed to tacrolimus according to a fast metabolism pharmacokinetic profile it led to reduced viability and increased Fn14 expression. We conclude from our data that the C/D ratio may be an appropriate tool for identifying patients at risk of developing calcineurin-inhibitor toxicity.
Children’s secure base script knowledge as a mediator between early life stress and later behavior problems

ABSTRACT Attachment theory posits that children’s interactions with caregivers contribute to internalized representations that reflects the common and recurring elements of sensitive caregiving interactions (i.e. the secure base script). These internalized representations are theorized to influence later adaptation, including the development of psychopathology. Given prior research suggesting that stress exposure may undermine secure base script knowledge (SBSK), this study evaluated SBSK development in early childhood as a mechanism by which childhood stress exposure may influence later adaptation. We hypothesized that children’s (N = 230; M age = 73.30 months, SD = 2.51, 50% girls; 45.7% Latinx) stress exposure would be associated with lower levels of SBSK at age 6, which, in turn, would contribute to increased internalizing and externalizing symptoms at age 8. SBSK emerged as a significant mechanism by which early life stress may contribute to later externalizing, but not internalizing, child behavior problems. These findings highlight the role of SBSK as a profitable focus for both risk identification and intervention efforts aimed at reducing behavioral maladaptation among stress-exposed children.
Birth weight, weight over the adult life course and risk of breast cancer

Breast cancer has been suggested to potentially have prenatal origins. We examined associations between birth weight, body mass index (BMI) at four‐time points over 25 years of adulthood, and risk of postmenopausal breast cancer, with emphasis on whether the association between birth weight and risk of breast cancer was mediated by weight and height changes over the adult life course. Postmenopausal women (n = 70,397) aged 50–79 years without breast cancer at enrollment (1993–1998) were followed up to 25 years. Weight and height were measured at baseline. Birth weight, and weights at ages 18, 35 and 50 were self‐reported. Breast cancer cases were centrally adjudicated. Compared to women with birth weight of 6–8 pounds, women with birth weight of <6 pounds had lower risk of breast cancer (HR = 0.88 95% CI: 0.79–0.99). 44% and 21% of the relationship between birth weight and breast cancer risk was mediated by adult height and weight at baseline, respectively. Birth weight of 8 pounds or more was not associated with risk of postmenopausal breast cancer. Weight gain in adulthood was associated with increased risk of breast cancer regardless of time periods. In conclusion, lower birthweight was associated with lower risk of postmenopausal breast cancer, and this reduction in risk was significantly mediated by childhood or adolescent growth, especially by adult height. Our data suggest that reaching and maintaining a healthy weight during adulthood is key in the prevention of breast cancer.
Long-term photostability in Terephthalate Metal Organic Frameworks.

Prolonged (weeks) UV-Vis irradiation under Ar of UiO-66(Zr), UiO66 Zr-NO 2 , MIL101 Fe, MIL125 Ti-NH 2 , MIL101 Cr and MIL101 Cr(Pt) shows that these MOFs undergo photodecarboxylation of benzenedicarboxylate (BDC) linker in a significant percentage depending on the structure and composition of the material. Routine characterization techniques such as XRD, UV-Vis spectroscopy and TGA fail to detect changes in the material, although porosity and surface area change upon irradiation of powders. In contrast to BCD containing MOFs, zeolitic imidazolate ZIF-8 does not evolve CO 2 or any other gas upon irradiation.
Comparison of the Structural Properties and Nutritional Fraction of Corn Starch Treated with Thermophilic GH13 and GH57 α-Glucan Branching Enzymes

Two thermophilic 1,4-α-glucan branching enzymes (GBEs), CbGBE from Caldicellulosiruptor bescii and PhGBE from Pyrococcus horikoshii, which belong to the glycoside hydrolase family 13 and 57 respectively, were cloned and expressed in Escherichia coli. Two GBEs were identified to have α-1,6 branching activity against various substrates, but substrate specificity was distinct. Starch was modified by two GBEs and their in vitro digestibility and structural properties were investigated. Short-branched A chains with a degree of polymerization (DP) of 6–12 increased with CbGBE-modified starch, increasing the proportion of slow digestible and resistant starch (RS) fractions. PhGBE-modified starch resulted in an increase in the RS fraction only by a slight increase in part of A chains (DP, 6–9). Compared to the proportion of control not treated with GBE, the proportion of α-1,6 linkages in CbGBE- and PhGBE-modified starch increased by 3.1 and 1.6 times. 13C cross polarization/magic angle sample spinning (CP/MAS) NMR and XRD pattern analysis described that GBE-modified starches reconstructed double helices but not the crystalline structure. Taken together, CbGBE and PhGBE showed distinct branching activities, resulting in different α-1,6 branching ratios and chain length distribution, and double helices amount of starch, ultimately affecting starch digestibility. Therefore, these GBEs can be used to produce customized starches with controlled digestion rates.
Towards a personalised approach in exercise-based cardiovascular rehabilitation: How can translational research help? A ‘call to action’ from the Section on Secondary Prevention and Cardiac Rehabilitation of the European Association of Preventive Cardiology

The benefit of regular physical activity and exercise training for the prevention of cardiovascular and metabolic diseases is undisputed. Many molecular mechanisms mediating exercise effects have been deciphered. Personalised exercise prescription can help patients in achieving their individual greatest benefit from an exercise-based cardiovascular rehabilitation programme. Yet, we still struggle to provide truly personalised exercise prescriptions to our patients. In this position paper, we address novel basic and translational research concepts that can help us understand the principles underlying the inter-individual differences in the response to exercise, and identify early on who would most likely benefit from which exercise intervention. This includes hereditary, non-hereditary and sex-specific concepts. Recent insights have helped us to take on a more holistic view, integrating exercise-mediated molecular mechanisms with those influenced by metabolism and immunity. Unfortunately, while the outline is recognisable, many details are still lacking to turn the understanding of a concept into a roadmap ready to be used in clinical routine. This position paper therefore also investigates perspectives on how the advent of ‘big data’ and the use of animal models could help unravel inter-individual responses to exercise parameters and thus influence hypothesis-building for translational research in exercise-based cardiovascular rehabilitation.
A Theory of Adaptive Intelligence and Its Relation to General Intelligence

Intelligence typically is defined as consisting of “adaptation to the environment” or in related terms. Yet, it is not clear that “general intelligence” or g, traditionally conceptualized in terms of a general factor in a psychometrically-based hierarchical model of intelligence, provides an optimal way of defining intelligence as adaptation to the environment. Such a definition of adaptive intelligence would need to be biologically based in terms of evolutionary theory, would need to take into account the cultural context of adaptation, and would need to take into account whether thought and behavior labeled as “adaptively intelligent” actually contributed to the perpetuation of the human and other species, or whether it was indifferent or actually destructive to this perpetuation. In this article, I consider the similarities and differences between “general intelligence” and “adaptive intelligence,” as well as the implications especially of the differences.
Non-Lytic Antibacterial Peptides That Translocate Through Bacterial Membranes to Act on Intracellular Targets

The advent of multidrug resistance among pathogenic bacteria has attracted great attention worldwide. As a response to this growing challenge, diverse studies have focused on the development of novel anti-infective therapies, including antimicrobial peptides (AMPs). The biological properties of this class of antimicrobials have been thoroughly investigated, and membranolytic activities are the most reported mechanisms by which AMPs kill bacteria. Nevertheless, an increasing number of works have pointed to a different direction, in which AMPs are seen to be capable of displaying non-lytic modes of action by internalizing bacterial cells. In this context, this review focused on the description of the in vitro and in vivo antibacterial and antibiofilm activities of non-lytic AMPs, including indolicidin, buforin II PR-39, bactenecins, apidaecin, and drosocin, also shedding light on how AMPs interact with and further translocate through bacterial membranes to act on intracellular targets, including DNA, RNA, cell wall and protein synthesis.
Transactional eHealth Literacy: Developing and Testing a Multi-Dimensional Instrument

Theoretically informed measures of eHealth literacy that consider the social affordances of eHealth are limited. This study describes the psychometric testing of a multi-dimensional instrument to measure functional, communicative, critical, and translational eHealth literacies, as informed by the Transactional Model of eHealth Literacy (TMeHL). A 3-phase rating scale construction process was conducted to engage eHealth experts and end-users. In Phase 1, Experts (N = 5) and end-users (N = 25) identified operational behaviors to measure each eHealth literacy dimension. End-users (N = 10) participated in think-aloud interviews to provide feedback on items reviewed and approved by experts. A field test was conducted with a random sample of patients recruited from a university-based research registry (N = 283). Factor analyses and Rasch procedures examined the internal structure of the scores produced by each scale. Pearson’s r correlations provided evidence for external validity of scores. The instrument measures four reliable (ω = .92-.96) and correlated (r= .44-.64) factors: functional (4 items), communicative (5 items), critical (5 items), and translational (4 items). Researchers and providers can use this new instrument as a theory-driven instrument to measure four eHealth literacies that are fundamental to the social affordances of the eHealth experience.
Patient diaries: Survey of paediatric intensive care units in the United Kingdom and Ireland.

AIM The aim of the study was to explore the incidence, use, and scope of patient diaries in paediatric intensive care units (PICUs) in the United Kingdom and Ireland. DESIGN This was an electronic survey sent to 30 PICUs in the United Kingdom and Ireland. RESULTS All PICUs (n = 30) responded, and 43% (n = 13) offered diaries. For those units that did not supply diaries, the reasons given were concerns around the legal and professional implication of using diaries. Parental/carer consent to use a diary was obtained informally (79%, n = 11), and once there was agreement to provide a diary to parents, diaries were usually started immediately (72%, n = 12). Parents were the main contributors to the diaries (94%, n = 17), and the diaries were populated with photographs (94%, n = 15), drawings (100%, n = 16), and stickers (94%, n = 15). The reasons for offering diaries were to fill gaps in memories, to engage with families, and to explain what has happened in lay language. The owner of the diary was reported to be the family (82%, n = 14) and the child (12%, n = 2). CONCLUSIONS The use of patient diaries is an evolving intervention in paediatric intensive care settings in the United Kingdom and Ireland. This national survey has provided a clearer picture of how this intervention is used in the United Kingdom and Ireland. PICU patient diaries are used in a significant number of units, and how these are used is relatively standardized, although in some different ways from general ICUs. RELEVANCE TO CLINICAL PRACTICE This survey provides a baseline for future exploration, understanding, and promotion of patient diaries, as a well evaluated tool for the critically ill child and his or her family.
Chain Substituted Cannabilactones with Selectivity for the CB2 Cannabinoid Receptor

In earlier work, we reported a novel class of CB2 selective ligands namely cannabilactones. These compounds carry a dimethylheptyl substituent at C3, which is typical for synthetic cannabinoids. In the current study with the focus on the pharmacophoric side chain at C3 we explored the effect of replacing the C1′-gem-dimethyl group with the bulkier cyclopentyl ring, and, we also probed the chain’s length and terminal carbon substitution with bromo or cyano groups. One of the analogs synthesized namely 6-[1-(1,9-dihydroxy-6-oxo-6H-benzo[c]chromen-3-yl) cyclopentyl] hexanenitrile (AM4346) has very high affinity (Ki = 4.9 nM) for the mouse CB2 receptor (mCB2) and 131-fold selectivity for that target over the rat CB1 (rCB1). The species difference in the affinities of AM4346 between the mouse (m) and the human (h) CB2 receptors is reduced when compared to our first-generation cannabilactones. In the cyclase assay, our lead compound was found to be a highly potent and efficacious hCB2 receptor agonist (EC50 = 3.7 ± 1.5 nM, E(max) = 89%). We have also extended our structure-activity relationship (SAR) studies to include biphenyl synthetic intermediates that mimic the structure of the phytocannabinoid cannabinodiol.
Endoscopy for gastroesophageal reflux disease and survival in esophageal adenocarcinoma

Gastroesophageal reflux disease (GERD) is a risk factor of esophageal adenocarcinoma (EAC) and the most common indication for upper gastrointestinal endoscopy. Yet, whether GERD or endoscopy practice influence survival in EAC is largely unknown and was assessed in our study.This nationwide cohort study included all Swedish residents diagnosed with EAC in 1997–2013 with follow‐up to 2018. Exposures were history of GERD and endoscopies prior to EAC. The main outcome was EAC‐specific 5‐year mortality. Multivariable Cox regression provided hazard ratios (HRs) with 95% confidence intervals (CIs) adjusted for potential confounders. Among 6,600 EAC patients (79.3% males, median age 70 years) followed for 9,138 person‐years, 440 (6.7%) had GERD and 592 (9.0%) had ≥1 endoscopy before EAC diagnosis. GERD was associated with a decreased risk of mortality (adjusted HR 0.71, 95% CI 0.64–0.80), which was only slightly attenuated by adjustment for prior endoscopies (HR 0.79, 95% CI 0.70–0.90), and further adjustments also for tumor stage and surgical resection (HR 0.74, 95% CI 0.62–0.89). Compared to EAC patients without prior endoscopy, mortality was unchanged in GERD patients having undergone 1 or 2 endoscopies before EAC diagnosis (HR 1.02, 95% CI 0.80–1.31, for 1 endoscopy; HR 0.90, 95% CI 0.63–1.30, for 2 endoscopies), while the mortality was decreased in patients with ≥3 endoscopies (HR 0.55, 95% CI 0.36–0.85). Our study indicates that GERD may be associated with a better prognosis in the event of EAC; however, the use of endoscopy screening has a limited impact on survival unless performed very frequently.
Patient Knowledge of Correct Dosage Regimen; The Need for Good Dispensing Practice

Background: The inappropriate use of medicine is a widespread problem, especially in developing countries. Proper dispensing practices as part of medication therapy increase benefits and minimize risks to the consumers. Objective: The purpose of this study was to assess patient knowledge of dosage regimen and the pharmacists dispensing practice. Method: A cross-sectional study design was conducted at Jimma Medical Center from March 1, 2018 to April 29, 2018. Data were collected prospectively using checklists and structured questionnaires. Results: Of the total prescribed drugs, 689 (74.25%) were actually dispensed, and 239 (34.7%) drugs were adequately labeled. The average dispensing and consultation times were 41.45 ± 12.1 and 49.13 ± 12 seconds, respectively. Of the total participants on exit interview, 267 (74.8%) correctly reported the dosage schedule of dispensed medicines. From the multivariate logistics regression analysis, language barrier (adjusted odds ratio [AOR] = 32.6, 95% confidence interval [CI] = 12.23-87.15), severity of health condition (AOR = 7.3, 95% CI = 2.70-19.56), and the number of drugs dispensed (AOR = 0.41, 95% CI = 0.18-0.87 [1 drug], AOR = 0.16, 95% CI = 0.61-0.42 [2 drugs]) have shown significant association with patient knowledge of dosage regimen. Conclusions: Majority of the patients did not receive the prescribed medicines from the outpatient pharmacy of Jimma Medical Center. Plus, only a few of the dispensed drugs contain all the necessary information. However, a large portion of the participants correctly reported the dosage schedule of their drugs.
Long-term Persistence of an Extensively Drug Resistant Subclade of Globally Distributed Pseudomonas aeruginosa Clonal Complex 446 in an Academic Medical Center.

BACKGROUND Antimicrobial resistance (AMR) is a major challenge in the treatment of infections caused by Pseudomonas aeruginosa. Highly drug-resistant infections are disproportionally caused by a small subset of globally distributed P. aeruginosa sequence types (STs), termed "high-risk clones. " We noted that clonal complex (CC) 446 (which includes STs 298 and 446) isolates were repeatedly cultured at one medical center and asked whether this lineage might constitute an emerging high-risk clone. METHODS We searched P. aeruginosa genomes from collections available from several institutions and from a public database for the presence of CC446 isolates. We determined antibacterial susceptibility using microbroth dilution and examined genome sequences to characterize the population structure of CC446 and investigate the genetic basis of AMR. RESULTS CC446 was globally distributed over 5 continents. CC446 isolates demonstrated high rates of AMR with 51.9% (28/54) being multi-drug resistant (MDR) and 53.6% of these (15/28) being extensively drug resistant (XDR). Phylogenetic analysis revealed that most MDR/XDR isolates belonged to a subclade of ST298 (designated ST298*) of which 100% (21/21) were MDR and 61.9% (13/21) were XDR. XDR ST298* was identified repeatedly and consistently at a single academic medical center from 2001-2017. These isolates harbored a large plasmid that carries a novel antibiotic resistance integron. CONCLUSIONS CC446 isolates are globally distributed with multiple occurrences of high AMR. The subclade ST298* is responsible for a prolonged epidemic (≥16 years) of XDR infections at an academic medical center. These findings indicate that CC446 is an emerging high-risk clone deserving further surveillance.
A New Multi-Robot Search Algorithm Using Probabilistic Finite State Machine and Lennard-Jones Potential Function

Swarm robotics is a decentralized approach to robotic systems. This paper investigates the problem of search and rescue using swarm robots. A multi-robot search algorithm using probabilistic finite state machine and interaction inspired by Lennard-Jones potential function has been proposed. Probabilistic finite state machine has been used to separate the tasks performed and to change coordination rules according to the circumstances and social probabilities. The approach is tested in various scenarios to test flexibility, scalability and robustness. The performance result is promising. Algorithmic complexity comparison with Robotic Darwinian Particle Swarm Optimization and Glowworm Swam Optimization appear favourable.
The value of a real face: Differences between affective faces and emojis in neural processing and their social influence on decision-making

ABSTRACT Emotional feedback is a crucial part of social interaction, since it may indicate motivations, intentions, and thus, the future behavior of interaction partners. Nowadays, social interaction has been enriched by artificial emotional feedback provided by emojis, which are the means of transporting emotions in mobile messengers. In this study, we examined the influence of emotional feedback by emojis compared to real faces on decision-making and neural processing. We modified the ultimatum game by including proposers represented both by emojis and human faces who reacted specifically toward acceptance or rejection of an offer. We show that proposers who reward acceptance with a smile cause the highest acceptance rates. Interestingly, acceptance rates did not differ between proposers represented by humans compared to emojis. Regarding electrophysiology, emojis evoked more negative N170 and N2 brain potentials compared to human faces both during a mere presentation and as feedback stimuli. Proposers that showed emotional facial expressions evoked larger N170 amplitudes as compared to neutral expressions. Especially the proposers represented by emojis evoked larger P3 amplitudes as feedback stimuli compared to human facial expressions. The comparison of emoji proposers with real-face proposers provides new insight into how relevant social cues influence behavior and its neural underpinnings.