Miracle-dz/UniFAR-FTUs huggingface dataset:
Featured Article: Strengths-Based, Clinic-Integrated Nonrandomized Pilot Intervention to Promote Type 1 Diabetes Adherence and Well-Being

Objective Given persistent challenges achieving optimal diabetes outcomes in adolescence, new interventions to support disease self-management and emotional well-being are needed. Approaches that emphasize adolescents' positive behaviors and attitudes ("strengths") are designed to incorporate positive provider communications into clinical encounters to encourage youths' engagement in adherence behaviors and enhance well-being. Methods This pilot study tested the feasibility, acceptability, and preliminary outcomes of a brief, strengths-based behavioral intervention for adolescents with type 1 diabetes. Adolescents (age 12-17 years) and parents were recruited, consented, and completed baseline and postintervention questionnaires. There was no randomization to a control group, and all participants received the pilot intervention. At the start of two clinic visits, diabetes care providers followed a semi-structured script to reinforce adolescents' diabetes-related strengths and adherence behaviors. Results Of 116 eligible families, 84 consented and 64 completed baseline (M age = 15.0 ± 1.8 years, 56% female, 69% White, M HbA1c = 8.6 ± 1.6%). Providers reported the intervention usually (95%) took <10 min to deliver. Participants and providers enjoyed the intervention and would like to see it as part of routine clinical care. Pre-post data indicated significant improvements in youth-rated diabetes strengths, adherence, burden, and relationship with provider, parent-reported diabetes burden, and provider-rated relationship with family (p < .05). Objectively measured adherence and glycemic control did not change. Conclusions This brief strengths-based, clinic-integrated intervention was feasible to conduct and stakeholders were satisfied. This intervention holds promise to have a positive impact on adolescents' diabetes adherence, well-being, and provider relationships. Lessons were learned to improve implementation and participant experience for a larger study.
A 10 year study of hospitalized atrial fibrillation-related stroke in England and its association with uptake of oral anticoagulation

Abstract Aims To determine whether changing patterns of anticoagulant use in atrial fibrillation (AF) have impacted on stroke rates in England. Methods and results English national databases, 2006–2016, were interrogated to assess stroke admissions and oral anticoagulant use. The number of patients with known AF increased linearly from 692 054 to 983 254 (prevalence 1.29% vs. 1.71%). Hospital episodes of AF-related stroke/100 000 AF patients increased from 80/week in 2006 to 98/week in 2011 and declined to 86/week in 2016 (2006–2011 difference 18.0, 95% confidence interval (CI) 17.9–18.1, 2011–2016 difference −12.0, 95% CI −12.1 to −11.9). Anticoagulant use amongst patients with CHA2DS2-VASc ≥2 increased from 48.0% to 78.6% and anti-platelet use declined from 42.9% to 16.1%; the greatest rate of change occurred in the second 5 year period (for anticoagulants 2006–2011 difference 4.8%, 95% CI 4.5–5.1%, 2011–2016 difference 25.8%, 95% CI 25.5–26.1%). After adjustment for AF prevalence, a 1% increase in anticoagulant use was associated with a 0.8% decrease in the weekly rate of AF-related stroke (incidence rate ratio 0.992, 95% CI 0.989–0.994). Had the use of anticoagulants remained at 2009 levels, 4068 (95% CI 4046–4089) more strokes would have been predicted in 2015/2016. Conclusion Between 2006 and 2016, AF prevalence and anticoagulant use in England increased. From 2011, hospitalized AF-related stroke rates declined and were significantly associated with increased anticoagulant uptake.
A common garden experiment with Porphyra umbilicalis (Rhodophyta) evaluates methods to study spatial differences in the macroalgal microbiome

While macroalgal microbiomes are the focus of many recent studies, there is little information about microbial spatial diversity across the thallus. Reliance on field material makes it difficult to discern whether recovered microbiomes belong to the host or its epiphytes, and technical comparisons of macroalgal samples for microbial studies are needed. Here, we use a common garden approach that avoids the problem of epiphytes, particularly at holdfasts, to examine the microbiome of Porphyra umbilicalis (strain Pum1). We used the V6 hypervariable region of the 16S rDNA with Illumina HiSeq sequencing and developed PNA clamps to block recovery of organelle V6 sequences. The common garden approach allowed us to determine differences in the microbiome at the holdfast versus blade margin. We found a notable increase in the relative abundance of Planctomycetes and Alphaproteobacteria at the holdfast, particularly of the possible symbiont Sulfitobacter sp. Nonadjacent 1.5 cm2 samples of blade margin had microbiomes that were not statistically different. The most abundant phylum in the overall microbiome was Proteobacteria, followed by Bacteroidetes. Because phycologists often work in remote sites, we compared three stabilization and preparation techniques and found silica gel desiccation/bead‐beating and flash‐freezing/lyophilization/bead‐beating to be interchangeable. Core taxa (≥0.1% of sequences) across treatments were similar and accounted for ≥95% of all sequences. Finally, statistical conclusions for all comparisons were the same, regardless of which microbial community analysis tool was used: mothur or minimum entropy decomposition.
The influence of sigma factors and ribosomal recognition elements on heterologous expression of cyanobacterial gene clusters in Escherichia coli

Cyanobacterial natural products offer new possibilities for drugs and lead compounds but many factors can inhibit the production of sufficient yields for pharmaceutical processes. While Escherichia coli and Streptomyces sp. have been used as heterologous expression hosts to produce cyanobacterial natural products, they have not met with resounding success largely due to their inability to recognize cyanobacterial promoter regions. Recent work has shown that the filamentous freshwater cyanobacterium Anabaena sp. strain PCC 7120 recognizes various cyanobacterial promoter regions and can produce lyngbyatoxin A from the native promoter. Introduction of Anabaena sigma factors into E. coli might allow the native transcriptional machinery to recognize cyanobacterial promoters. Here, all 12 Anabaena sigma factors were expressed in E. coli and subsets were found to initiate transcription from several cyanobacterial promoters based on transcriptional fusions to the chloramphenicol acetyltransferase (CAT) reporter. Expression of individual Anabaena sigma factors in E. coli did not result in lyngbyatoxin A production from its native cyanobacterial gene cluster, possibly hindered by deficiencies in recognition of cyanobacterial ribosomal binding sites by native E. coli translational machinery. This represents an important step toward engineering E. coli into a general heterologous expression host for cyanobacterial biosynthetic gene cluster expression.
Ghrelin modulates mesolimbic reactivity to alcohol cues in alcohol‐addicted subjects: a functional imaging study

Ghrelin has been shown to be involved in the pathophysiology of alcohol dependence, affecting alcohol self‐administration and craving. However, the mechanism of action in alcohol dependence still has to be determined. We thus investigated whether ghrelin is associated with mesolimbic cue reactivity to alcohol cues and alcohol craving in recently detoxified alcohol‐addicted subjects. We included 41 recently detoxified alcohol‐dependent individuals. Functional magnetic resonance imaging (fMRI) was used to study mesolimbic cue reactivity during the presentation of alcohol‐related pictures. Additionally, we assessed patients' alcohol craving using the Alcohol Urge Questionnaire and a visual analogue scale. Plasma concentrations of total and acylated (activated) ghrelin were measured in parallel to the fMRI session. The association between ghrelin plasma concentrations, mesolimbic cue reactivity and alcohol craving was assessed by performing correlation and mediation analyses. Alcohol‐induced brain response in a network of brain clusters, including the right and left ventral striatum, showed a significant positive association with acylated ghrelin plasma concentration. Additionally, acylated ghrelin was significantly associated with craving. Mediation analyses showed that the association between acylated ghrelin plasma concentration and alcohol craving is mediated by a cue‐induced brain response in the ventral striatum. Based on the finding that ghrelin modulates mesolimbic reactivity to alcohol cues, the following should be considered: If alcohol craving and the appetitive status were interrelated, this has to be taken into account when implementing fMRI studies for addictive disorders. Moreover, appetite regulation seems to represent a valid treatment target for reducing cue reactivity in addictive disorders.
High‐dose therapy and autologous stem cell transplantation in marginal zone lymphomas: a retrospective study by the EBMT Lymphoma Working Party and FIL‐GITMO

The role of autologous stem cell transplantation (ASCT) in patients with marginal zone lymphoma (MZL) is debatable. This study investigated the outcome and prognostic factors affecting the outcome of patients undergoing ASCT for MZL. Eligible patients had non‐transformed nodal, extra‐nodal (MALT) or splenic MZL (SMZL), aged ≥18 years, who underwent a first ASCT between1994 and 2013 and were reported to the European Society for Blood and Marrow Transplantation, Fondazione Italiana Linfomi or Gruppo Italiano Trapianto Di Midollo Osseo registries. The study included 199 patients, [111 MALT lymphoma, 55 nodal MZL (NMZL) and 33 SMZL]. Median age at transplantation was 56 years. The median number of prior therapies was 2 (range 1–8), including rituximab in 71%. 95% had chemosensitive disease. 89% received a chemotherapy‐based high‐dose regimen. There were no significant differences in patient and transplant characteristics between the 3 histological subtypes except for a lower percentage of patients previously treated with rituximab in the MALT sub‐group and more transplants performed in recent years in the other sub‐groups. After a median follow‐up of 5 years, 5‐year cumulative incidence of relapse/progression and non‐relapse mortality were 38% and 9%, respectively. Five‐year event‐free survival (EFS) and overall survival (OS) were 53% and 73%, respectively. Five‐year cumulative incidence of second malignancies was 6%. Multivariate analysis revealed age ≥65 years was associated with a shorter EFS and OS. In addition, patients with SMZL had a shorter OS than those with MALT. ASCT may provide clinical benefit in MZL patients who have failed multiple lines of chemoimmunotherapy.
Measurement of Cortisol and Testosterone in Athletes: Accuracy of Liquid Chromatography–Tandem Mass Spectrometry Assays for Cortisol and Testosterone Measurement in Whole-Blood Microspecimens

Abstract Fragala, MS, Goldman, SM, Goldman, MM, Bi, C, Colletti, JD, Arent, SM, Walker, AJ, and Clarke, NJ. Measurement of cortisol and testosterone in athletes: Accuracy of LC-MS/MS assays for cortisol and testosterone measurement in whole-blood microspecimens. J Strength Cond Res 32(9): 2425–2434, 2018—Biomarker monitoring provides insight into athletes' training tolerance but is limited by the need for office-based specimen collection. To facilitate self-collection during training, we developed liquid chromatography–tandem mass spectrometry-based tests that measure circulating total cortisol and testosterone using a finger stick volumetric absorptive microsampler. Here, we describe the analytical validation of these tests. Forty-six Division I athletes (18–22 years, 30 women, 16 men) provided a 20-µL finger stick microspecimen and a 5-ml venous blood specimen from the forearm; the venous blood sample was analyzed using both normal volume serum analysis and analysis of dried whole blood (from the microsampler). Liquid chromatography–tandem mass spectrometry on standard serum specimens obtained by venipuncture yielded total cortisol levels of 26.2 ± 11.6 µg·dl−1 (women and men), and total testosterone levels of 37 ± 17 ng·dl−1 in women and 564 ± 171 ng·dl−1 in men. Analytical measurement ranges of the microspecimen assay were 0.3–440 µg·dl−1 (CV <9%) for cortisol and 15 to 20,000 ng·dl−1 (CV <9%) for testosterone. Deming regression and Pearson correlation indicated good test accuracy for the microspecimen tests compared with venipuncture tests for cortisol (y = 0.98x + 1.34, 95% CI of slope = 0.83–1.14; r = 0.92, p < 0.0001) and testosterone (y = 1.06x − 0.01, 95% CI of slope = 0.99–1.14; r = 0.99, p < 0.0001). Similarly, high agreement was observed between finger stick and venous microspecimens for cortisol (y = 1.00x + 0.65, 95% CI of slope = 0.9–1.11; r = 0.96, p < 0.001) and testosterone (y = 0.97x + 2.75, 95% CI of slope = 0.9–1.03; r = 0.99, p < 0.001). These findings suggest the viability of finger stick collection whole-blood microspecimens for assessment of total cortisol and testosterone in athletes.
A proposal for a new PhD level curriculum on quantitative methods for drug development

This paper provides an overview of “Improving Design, Evaluation and Analysis of early drug development Studies” (IDEAS), a European Commission–funded network bringing together leading academic institutions and small‐ to large‐sized pharmaceutical companies to train a cohort of graduate‐level medical statisticians. The network is composed of a diverse mix of public and private sector partners spread across Europe, which will host 14 early‐stage researchers for 36 months. IDEAS training activities are composed of a well‐rounded mixture of specialist methodological components and generic transferable skills. Particular attention is paid to fostering collaborations between researchers and supervisors, which span academia and the private sector. Within this paper, we review existing medical statistics programmes (MSc and PhD) and highlight the training they provide on skills relevant to drug development. Motivated by this review and our experiences with the IDEAS project, we propose a concept for a joint, harmonised European PhD programme to train statisticians in quantitative methods for drug development.
Growing with Wheat and Barley Rusts for Three Decades

*S.N. Dasgupta Memorial Award Lecture, delivered at 69th Annual Meeting of Indian Phytopathological Society and National Symposium on “Diagnosis of and management of plant diseases: Integrated approaches and recent trends”. January 9-11, 2017 at ICAR Complex for NEH Region, Umiam, Shillong, Meghalaya Email: scbfdl@hotmail.com I feel honoured and elated for being conferred S.N. Dasgupta memorial award. I am grateful to the Indian Phytopathological Society to bestow this honour upon me which is named after one of the great Scientists of all the times. Dr. Dasgupta belonged to a family of distinguished people. He did pioneer research on physiological plant pathology, was an excellent Fungal taxonomist who rose to become the Vice Chancellor of Kalyani University, a position he served for two terms. I think he would have been very happy today to see that I would be discussing very important disease rust and sharing my experience with this august gathering, on ways and means to secure wheat. This crop is synonym to economic health and nutritional security of many countries with India no exception. Today we remember Dr. Dasgupta for the work done by him for the progress of biosciences and this lecture is a tribute to the great soul.
Reducing reward responsivity and daily food desires in female dieters through domain-specific training

ABSTRACT According to the strength model, self-regulation relies on a domain-general capacity that may be strengthened by training. From this perspective, training self-regulation in one domain may transfer to other domains. Here we used two inhibitory training paradigms, a domain-general and domain-specific stop-signal training task and compared their effects on brain reward activity as well as daily food desires in female dieters. Before and after the training, functional magnetic resonance imaging was used to assess food cue-reactivity, coupled with one week of smart-phone ecological momentary assessments to examine eating urges. Whereas the food-specific inhibitory training was successful in reducing both food cue-reactivity and food desires, the domain-general (sound-cue) training showed no transfer effects. These findings suggest that domain-specific training may be a more effective method for supporting self-regulation than domain-general approaches aimed at strengthening self-regulation across domains.
Protein ORIGAMI: A program for the creation of 3D paper models of folded peptides

Protein ORIGAMI (http://ibg.kit.edu/protein_origami) is a browser‐based web application that allows the user to create straightforward 3D paper models of folded peptides for research, teaching and presentations. An amino acid sequence can be turned into α‐helices, β‐strands and random coils that can be printed out and folded into properly scaled models, with a color code denoting the biophysical characteristics of each amino acid residue (hydrophobicity, charge, etc.). These models provide an intuitive visual and tactile understanding of peptide interactions with other partners, such as helix‐helix assembly, oligomerization, membrane binding, or pore formation. Helices can also be displayed as a helical wheel or helical mesh in 2D graphics, to be used in publications or presentations. The highly versatile programme Protein ORIGAMI is also suited to create less conventional helices with arbitrary pitch (e.g., 310‐helix, π‐helix, or left‐handed helices). Noncanonical amino acids, labels and different terminal modifications can be defined and displayed at will, and different protonation states can be shown. In addition to the web application, the program source code can be downloaded and installed locally on a PC. The printed paper models can be readily used for daily research and discussions, just as for educational purposes and teaching. © 2018 by The International Union of Biochemistry and Molecular Biology, 46:403–409, 2018.
Mothers’ experiences of their work as healthcare assistants for their chronic disabled child

Abstract Background: To the best of our knowledge, no research of the work situation of full-time, paid, parental HC assistants has been done. Aim: To examine how parents experienced their work as HC assistants for their chronic disabled child. Methods: Semi-structured interviews based on the Work Environment Impact Scale (WEIS-S) were done with nine mothers who had a child aged 8-17 years old with a cognitive or/and physical chronic disability. Content analysis was used with the Model Of Human Occupation as a framework. Results: The studied mothers always needed to be stand-by for their child, and they highlighted physical and psychological health problems caused by their work situation. There were several difficulties working in different environments because of the child’s need of technical devices. Further they described the support from their employers as important and in general the participants perceived a lack of understanding about their work situation in the society. Conclusion: The mothers in the present study had unclear job descriptions, they often worked more than full-time, and had low occupational balance. Significance: Occupational therapists could improve the HC assistants’ work place focusing on the physical and psycho-social work environment as well as on their occupational balance.
LigVoxel: inpainting binding pockets using 3D‐convolutional neural networks

Motivation: Structure‐based drug discovery methods exploit protein structural information to design small molecules binding to given protein pockets. This work proposes a purely data driven, structure‐based approach for imaging ligands as spatial fields in target protein pockets. We use an end‐to‐end deep learning framework trained on experimental protein‐ligand complexes with the intention of mimicking a chemist's intuition at manually placing atoms when designing a new compound. We show that these models can generate spatial images of ligand chemical properties like occupancy, aromaticity and donor‐acceptor matching the protein pocket. Results: The predicted fields considerably overlap with those of unseen ligands bound to the target pocket. Maximization of the overlap between the predicted fields and a given ligand on the Astex diverse set recovers the original ligand crystal poses in 70 out of 85 cases within a threshold of 2 Å RMSD. We expect that these models can be used for guiding structure‐based drug discovery approaches. Availability and implementation: LigVoxel is available as part of the PlayMolecule.org molecular web application suite. Supplementary information: Supplementary data are available at Bioinformatics online.
Therapists’ experience of the cognitive orientation to daily occupational performance (CO-OP) approach: Shifting from conventional practice

Abstract Background: The CO-OP ApproachTM has been increasingly used in research and practice, yet its critical elements and implementation challenges are largely undescribed. Obtaining therapists’ perspectives on CO-OP may reveal insights into potential critical and mediating factors. Aim/Objective: To explore the experiences of CO-OP therapists by understanding their perceptions on the approach compared with conventional practice, and by identifying mediating factors in its implementation. Material and Method: This exploratory study utilized a qualitative descriptive design. A purposive sample of occupational therapists (n = 3) was interviewed. Data were analyzed using thematic analysis and themes were validated within a focus group. Results/Findings: Three themes were identified: ‘CO-OP works,’ ‘CO-OP delivery is mediated by contextual factors,’ and ‘CO-OP shifts the therapeutic approach. ’ Therapists perceived CO-OP to be efficacious for client-centred goal attainment. Guided discovery and the problem-solving strategy were identified as unique and challenging CO-OP elements. Mediating factors such as level of cognitive impairment and quality of family member involvement may affect CO-OP efficacy. Conclusions: Therapists found CO-OP to be efficacious and adopted unique elements into their professional approaches. Significance: This is the first study to investigate CO-OP therapists’ experiences. Future research is recommended to enhance training of therapists in key CO-OP features.