Miracle-dz/UniFAR-FTUs huggingface dataset:
Barriers and facilitators to physical activity among children, adolescents, and young adults with cystic fibrosis: a systematic review and thematic synthesis of qualitative research

Objectives Physical activity is widely recommended in the treatment and management of cystic fibrosis (CF). Despite the numerous physical and psychological benefits, many young people with CF are not achieving the recommended levels of physical activity. The aim of this systematic review was to identify and synthesise available qualitative investigations exploring the motives for, barriers to and facilitators of physical activity among young people with CF. Methods The following six electronic databases were systematically searched: Applied Social Sciences Index and Abstracts (ASSIA), CINAH, EMBASE, MEDLINE, MEDLINE-in-process, PsycINFO up to August 2019. Keywords were used to identify qualitative research that explored engagement in physical activity among young people with CF. Titles and abstracts were screened by two independent reviewers, and potentially relevant articles were retrieved in full. Articles were eligible for inclusion if they employed any qualitative method and recruited participants under the age of 24 years with CF. Risk of bias of included studies was assessed via the Critical Appraisal Skills Programme. Results were synthesised using a thematic approach. Results Seven studies met our inclusion criteria and were included in the review. Overall, studies were of moderate to high quality. Thematic synthesis identified nine main themes that encompass motives for, barriers to and facilitators of physical activity among young people with CF. These were (1) Perceptions of physical activity. (2) Value attributed to physical activity. (3) Social influences. (4) Competing priorities. (5) Fluctuating health. (6) Normality. (7) Control beliefs. (8) Coping strategies. (9) Availability of facilities. Previous reviews have been unable to identify intervention characteristics that influence physical activity behaviour. Conclusions This review provides detailed information on the physical (biological—clinical), psychological, social and environmental influences on physical activity behaviour, thus providing numerous targets for future interventions. This in turn could facilitate promotion of physical activity among young people with CF.
Topic-driven toxicity: Exploring the relationship between online toxicity and news topics

Hateful commenting, also known as ‘toxicity’, frequently takes place within news stories in social media. Yet, the relationship between toxicity and news topics is poorly understood. To analyze how news topics relate to the toxicity of user comments, we classify topics of 63,886 online news videos of a large news channel using a neural network and topical tags used by journalists to label content. We score 320,246 user comments from those videos for toxicity and compare how the average toxicity of comments varies by topic. Findings show that topics like Racism, Israel-Palestine, and War & Conflict have more toxicity in the comments, and topics such as Science & Technology, Environment & Weather, and Arts & Culture have less toxic commenting. Qualitative analysis reveals five themes: Graphic videos, Humanistic stories, History and historical facts, Media as a manipulator, and Religion. We also observe cases where a typically more toxic topic becomes non-toxic and where a typically less toxic topic becomes “toxicified” when it involves sensitive elements, such as politics and religion. Findings suggest that news comment toxicity can be characterized as topic-driven toxicity that targets topics rather than as vindictive toxicity that targets users or groups. Practical implications suggest that humanistic framing of the news story (i.e., reporting stories through real everyday people) can reduce toxicity in the comments of an otherwise toxic topic.
Clinical and Genetic Risk Prediction of Cognitive Impairment After Blood or Marrow Transplantation for Hematologic Malignancy.

PURPOSE Using a candidate gene approach, we tested the hypothesis that individual single nucleotide polymorphisms (SNPs) and gene-level variants are associated with cognitive impairment in patients with hematologic malignancies treated with blood or marrow transplantation (BMT) and that inclusion of these SNPs improves risk prediction beyond that offered by clinical and demographic characteristics. PATIENTS AND METHODS In the discovery cohort, BMT recipients underwent a standardized battery of neuropsychological tests pre-BMT and at 6 months, 1 year, 2 years, and 3 years post-BMT. Associations between 68 candidate genes and cognitive impairment were assessed using generalized estimating equation models. Elastic-Net regression was used to build Base (sociodemographic), Clinical, and Combined (Base plus Clinical plus genetic) risk prediction models of post-BMT impairment. An independent nonoverlapping cohort from the BMT Survivor Study with self-report of learning/memory problems (as identified by their health care provider) was used for model replication. RESULTS The discovery cohort included 277 participants (58.5% males; 68.6% non-Hispanic whites; and 46.6% allogeneic BMT recipients). Adjusting for BMT type, age at BMT, sex, race/ethnicity, and cognitive reserve, SNPs in the blood-brain barrier, telomere homeostasis, and DNA repair genes were significantly associated with cognitive impairment. Compared with the Clinical Model, the Combined Model had higher predictive power in both the discovery cohort (mean area under the receiver operating characteristic curve [AUC], 0.89; 95% CI, 0.85 to 0.93 v 0.77; 95% CI, 0.71 to 0.83; P = 1.24 × 10-9) and the replication cohort (AUC, 0.71; 95% CI, 0.66 to 0.76 v 0.63; 95% CI, 0.57 to 0.68; P = .004). CONCLUSION Inclusion of candidate genetic variants enhanced the prediction of risk of post-BMT cognitive impairment beyond that offered by demographic/clinical characteristics and represents a step toward a personalized approach to managing patients at high risk for cognitive impairment after BMT.
Retroperitoneal Fibrosis and Deep Vein Thrombosis in a Patient With Scleroderma

68-year-old man presented with edema in his left leg and A thickened skin of both legs persisting for 5 years. Computed tomography (CT) showed thickened soft tissues of the pelvic wall (Fig. 1). The diagnosis of retroperitoneal fibrosis with scleroderma was established. Physical examination revealed thickened and hardened skin of both lower limbs. C-reactive protein (CRP) level, erythrocyte sedimentation rate (ESR), and serum immunoglobulin G4 level were within the normal limits (2.88 mg/L, 22 mm/h, and 49 mg/dL, respectively). Antinuclear antibodies, antiphospholipid antibodies, anti-Scl-70 antibodies, and human leukocyte antigen B27 were negative. Skin biopsy confirmed the presence of scleroderma (Fig. 2). After the diagnosis, we prescribed methylprednisolone (40 mg, once per day) and cyclophosphamide (0.4 g, every 2 weeks). The dosages of both drugs were gradually reduced. At 6 months after the treatment, the lower-limb edema had improved and the skin had softened. Abdominal CT showed significantly reduced presacral and retroperitoneal lesions (Fig. 3a). The patient was treated with corticosteroids for 1 year and intermittent cyclophosphamide for 5 years after discharge. Follow-up evaluations were performed at 3, 6, and 9 years (Fig. 3b–d). At 6 years (1 year after cyclophosphamide withdrawal), the patient developed deep vein thrombosis (DVT) in his left lower limb and was treated with anticoagulants (Fig. 4). At 9 years, abdominal CT showed the development of mild retroperitoneal soft tissue fibrosis (Fig. 3d).
Dietary supplementation with copper nanoparticles influences the markers of oxidative stress and modulates vasodilation of thoracic arteries in young Wistar rats

We aimed to study the physiological effects of diet supplemented with copper (Cu) nanoparticles (NPs). During the eight weeks of the experiment, young Wistar rats (at seven weeks of age, n = 9) were supplemented with 6.5 mg of Cu either as NPs or carbonate salt (Cu6.5). A diet that was not supplemented with Cu served as a negative control (Cu0). The impact of nano Cu supplementation on lipid (reflected as thiobarbituric acid reactive substances–TBARS) and protein peroxidation (thiol and carbonyl groups) in blood plasma as well as the influence on the vasodilatory mechanism(s) of isolated rat thoracic arteries were studied. Supplementation with Cu enhanced lipid peroxidation (TBARS) in NP6.5 (x2.4) and in Cu6.5 (x1.9) compared to the negative control. Significant increase in TBARS was also observed in NP6.5 (x1.3) compared to the Cu6.5 group. The level of thiol groups increased in NP6.5 (x1.6) compared to Cu6.5. Meanwhile, significant (x0.6) decrease was observed in the Cu6.5 group compared to the negative control. Another marker of protein oxidation, carbonyl groups increased in NP6.5 (x1.4) and Cu6.5 (x2.3) compared to the negative control. However significant difference (x0.6) was observed between NP6.5 and Cu6.5. Arteries from Cu supplemented rats exhibited an enhanced vasodilation to gasotransmitters: nitric oxide (NO) and carbon monoxide (CO). An enhanced vasodilation to NO was reflected in the increased response to acetylcholine (ACh) and calcium ionophore A23187. The observed responses to ACh and CO releasing molecule (CORM-2) were more pronounced in NP6.5. The activator of cGMP-dependent protein kinases (8-bromo-cGMP) induced similar vasodilation of thoracic arteries in NP6.5 and Cu0 groups, while an increased response was observed in the Cu6.5 group. Preincubation with the inducible nitric oxide (iNOS) synthase inhibitor– 1400W, decreased the ACh-induced vasodilation in NP6.5, exclusively. Meanwhile the eicosanoid metabolite of arachidonic acid (20-HETE) synthesis inhibitor–HET0016, enhanced vasodilation of arteries from Cu0 group. In conclusion, this study demonstrates that supplementation with nano Cu influences oxidative stress, which further has modified the vascular response.
Comparison of a modified Sequential Organ Failure Assessment Score using RASS and FOUR

Objective ICU severity scores such as the Sequential Organ Failure Assessment (SOFA) determine neurologic dysfunction based on the Glasgow Coma Scale, a tool that may be limited in a critically ill population. It remains unknown whether alternative methods to assess for neurologic dysfunction, such as FOUR and RASS, are superior. This study aimed to determine the predictive performance of a modified SOFA tool in a large Brazilian ICU cohort. Design Prospective cohort single center study. Setting Mixed surgical and medical ICU in Salvador, Bahia, Brazil between August 2015 and December 2018. Patients All acutely ill ICU admissions, other than postoperative patients or those with insufficient data, were eligible for study inclusion. Measurements and main results 2147 patients were admitted to the ICU, of which 999 meeting inclusion criteria were included in the final analysis with a median age of 72 years (IQR 58–83) and a female predominance 545 (54%). The SOFA score using GCS, RASS and FOUR for the neurologic component performed marginally in the ability to predict general ICU mortality (SOFAGCS AUC 0.74 vs SOFARASS AUC 0.71 and SOFAFOUR AUC 0.67), with SOFAFOUR performing significantly lower compared to either SOFARASS and SOFAGCS (p<0.04, p<0.004 respectively). All three scores demonstrated decreased discriminate function in the mechanically ventilated population (SOFAGCS AUC 0.70 vs SOFARASS AUC 0.70 and SOFAFOUR AUC 0.55), though SOFAFOUR remained significantly worse when compared to SOFAGCS or SOFARASS (p = 0.034, p = 0.014, respectively). Furthermore, performance was poor in a subset of patients with sepsis (n = 145) at time of admission (SOFAGCS AUC 0.66 vs SOFARASS AUC 0.55 and SOFAFOUR AUC 0.56). Conclusion Modification of the neurologic component in the SOFA score does not appear to improve mortality prediction in the ICU.
HIV-related Cardiovascular Diseases: the Search for a Unifying Hypothesis.

Although the extensive roll-out of antiretroviral (ARV) therapy resulted in a longer life expectancy for people living with human immunodeficiency virus (PLHIV), such individuals display a relatively increased occurrence of cardiovascular diseases (CVD). This health challenge stimulated significant research interests in the field, leading to an improved understanding of both lifestyle-related risk factors and the underlying mechanisms of CVD onset in PLHIV. However, despite such progress the precise role of various risk factors and mechanisms underlying the development of HIV-mediated CVD still remain relatively poorly understood. We therefore review CVD onset in PLHIV and focus on a) the spectrum of cardiovascular complications that typically manifest in such persons and b) underlying mechanisms that are implicated in this process. Here the contributions of such factors and modulators, and underlying mechanisms are considered in a holistic and integrative manner to generate a unifying hypothesis that includes identification of the core pathways mediating CVD onset. The review focuses on the sub-Saharan African context as there are relatively high numbers of PLHIV residing within this region indicating that the greater CVD risk will increasingly threaten the well-being and health of its citizens. It is our opinion that such an approach helps point the way for future research efforts to improve treatment strategies and/or lifestyle-related modifications for PLHIV.
Biochemical characterization of acyl activating enzymes for side chain moieties of Taxol and its analogs

Taxol (paclitaxel) is a very widely used anticancer drug, but its commercial sources mainly consist of stripped bark or suspension cultures of members of the plant genus Taxus. Taxol accumulates as part of a complex mixture of chemical analogs, termed taxoids, which complicates its production in pure form, highlighting the need for metabolic engineering approaches for high-level Taxol production in cell cultures or microbial hosts. Here, we report on the characterization of acyl-activating enzymes (AAEs) that catalyze the formation of CoA esters of different organic acids relevant for the N-substitution of the 3-phenylisoserine side chain of taxoids. On the basis of similarities to AAE genes of known function from other organisms, we identified candidate genes in publicly available transcriptome data sets obtained with Taxus × media. We cloned 17 AAE genes, expressed them heterologously in Escherichia coli, purified the corresponding recombinant enzymes, and performed in vitro assays with 27 organic acids as potential substrates. We identified TmAAE1 and TmAAE5 as the most efficient enzymes for the activation of butyric acid (Taxol D side chain), TmAAE13 as the best candidate for generating a CoA ester of tiglic acid (Taxol B side chain), TmAAE3 and TmAAE13 as suitable for the activation of 4-methylbutyric acid (N-debenzoyl-N-(2-methylbutyryl)taxol side chain), TmAAE15 as a highly efficient candidate for hexanoic acid activation (Taxol C side chain), and TmAAE4 as suitable candidate for esterification of benzoic acid with CoA (Taxol side chain). This study lays important groundwork for metabolic engineering efforts aimed at improving Taxol production in cell cultures.
Advanced Hand Gesture Prediction Robust to Electrode Shift with an Arbitrary Angle

Recent advances in myoelectric controlled techniques have made the surface electromyogram (sEMG)-based sensing armband a promising candidate for acquiring bioelectric signals in a simple and convenient way. However, inevitable electrode shift as a non-negligible defect commonly causes a trained classifier requiring continuous recalibrations. In this study, a novel hand gesture prediction is firstly proposed; it is robust to electrode shift with arbitrary angle. Unlike real-time recognition which outputs target gestures only after the termination of hand motions, our proposed advanced prediction can provide the same results, even before the completion of signal collection. Moreover, by combining interpolated peak location and preset synchronous gesture, the developed simplified rapid electrode shift detection and correction at random rather than previous fixed angles are realized. Experimental results demonstrate that it is possible to achieve both electrode shift detection with high precision and gesture prediction with high accuracy. This study provides a new insight into electrode shift robustness which brings gesture prediction a step closer to practical applications.
A novel locus from the wild allotetraploid rice species Oryza latifolia Desv. confers bacterial blight (Xanthomonas oryzae pv. oryzae) resistance in rice (O. sativa)

Bacterial blight caused by Xanthomonas oryzae pv. oryzae (Xoo) is a major limiting factor to rice productivity worldwide. Genetic control through the identification of novel sources of bacterial blight resistance and their utilization in resistance breeding remains the most effective and economical strategy to manage the disease. Here we report the identification of a novel locus from the wild Oryza species, Oryza latifolia, conferring a race-specific resistance to Philippine Xoo race 9A (PXO339). The locus was identified from two introgression lines i.e. WH12-2252 and WH12-2256 that segregated from O. latifolia monosomic alien addition lines (MAALs). The discrete segregation ratio of susceptible and resistant phenotypes in the F2 (χ2[3:1] = 0.22 at p>0.05) and F3 (χ2[3:1] = 0.36 at p>0.05) populations indicates that PXO339 resistance in the MAAL-derived introgression lines (MDILs) is controlled by a single, recessive gene. Genotyping of a total of 216 F2, 1130 F3 and 288 F4 plants derived from crossing either of the MDILs with the recurrent parent used to generate the MAALs narrowed the candidate region to a 1,817 kb locus that extends from 10,425 to 12,266 kb in chromosome 12. Putative candidate genes that were identified by data mining and comparative sequence analysis can provide targets for further studies on mapping and cloning of the causal gene for PXO339 resistance in the MDILs. To our knowledge, this is the first report of a genetic locus from the allotetraploid wild rice, O. latifolia conferring race-specific resistance to bacterial blight.
CCAAT enhancer binding protein alpha (CEBPA) biallelic acute myeloid leukaemia: cooperating lesions, molecular mechanisms and clinical relevance

Recent advances in sequencing technologies have allowed for the identification of recurrent mutations in acute myeloid leukaemia (AML). The transcription factor CCAAT enhancer binding protein alpha (CEBPA) is frequently mutated in AML, and biallelic CEBPA‐mutant AML was recognised as a separate disease entity in the recent World Health Organization classification. However, CEBPA mutations are co‐occurring with other aberrations in AML, and together these lesions form the clonal hierarchy that comprises the leukaemia in the patient. Here, we aim to review the current understanding of co‐occurring mutations in CEBPA‐mutated AML and their implications for disease biology and clinical outcome. We will put emphasis on patterns of cooperation, how these lesions cooperate with CEBPA mutations and the underlying potential molecular mechanisms. Finally, we will relate this to patient outcome and future options for personalised medicine.
Arginine in C9ORF72 Dipolypeptides Mediates Promiscuous Proteome Binding and Multiple Modes of Toxicity*

C9ORF72-associated Motor Neuron Disease patients feature abnormal expression of 5 dipeptide repeat (DPR) polymers. We found the most toxic DPRs, PR and GR, were particularly promiscuous binders to endogenous proteins. This included ribosomal proteins, translation initiation factors and translation elongation factors. The corresponding biological impacts were multipronged and included stalling of ribosomes during translation, hypomethylation of endogenous proteins, and the destabilization of the actin cytoskeleton. The findings point to new mechanisms of toxicity in disease caused by arg-rich DPRs. Graphical Abstract Highlights Quantitative proteome interactions with 5 different C9ORF72 dipolypeptides (DPRs). The arg-rich DPRs promiscuously bound to the proteome compared with the other DPRs. Long repeat lengths of arg-rich DPRs, but not short lengths, stalled ribosomes. The arg-rich DPRs also reduced arginine methylation and actin cytoskeleton assembly. C9ORF72-associated Motor Neuron Disease patients feature abnormal expression of 5 dipeptide repeat (DPR) polymers. Here we used quantitative proteomics in a mouse neuronal-like cell line (Neuro2a) to demonstrate that the Arg residues in the most toxic DPRS, PR and GR, leads to a promiscuous binding to the proteome compared with a relative sparse binding of the more inert AP and GA. Notable targets included ribosomal proteins, translation initiation factors and translation elongation factors. PR and GR comprising more than 10 repeats appeared to robustly stall on ribosomes during translation suggesting Arg-rich peptide domains can electrostatically jam the ribosome exit tunnel during synthesis. Poly-GR also recruited arginine methylases, induced hypomethylation of endogenous proteins, and induced a profound destabilization of the actin cytoskeleton. Our findings point to arginine in GR and PR polymers as multivalent toxins to translation as well as arginine methylation that may explain the dysfunction of biological processes including ribosome biogenesis, mRNA splicing and cytoskeleton assembly.
Traditional Yellow Dyes Used in the 21st Century in Central Iran: The Knowledge of Master Dyers Revealed by HPLC-DAD and UHPLC-HRMS/MS

This work provides new knowledge on natural yellows used in Iran. Seven biological sources were selected based on interviews with dye masters in Isfahan workshops (Iran). Delphinium semibarbatum, Eremostachys laevigata, Prangos ferulacea, Morus alba, Pistacia vera, Punica granatum, and Vitis vinifera are currently used in these workshops. Aiming to study the dye composition of wool samples dyed with the extracts of the selected biological sources, and the changes induced by the dyeing procedures in the original chemical composition of the plant extract, raw materials and dyed wool (by us and in the workshops) were analyzed by HPLC–DAD and UHPLC–HRMS/MS. In solutions extracted from the textiles, the main yellows for E. laevigata are luteolin-O-glycosides. In the other plant sources, the main chromophores are based on 3-O-glycosides of kaempferol, quercetin, and isorhamnetin. In pistachio hulls, myricitin derivatives were detected and we propose their use as markers. Generally, the solutions extracted from the wool displayed a higher amount of more polar compounds, but also a higher amount of aglycones. Importantly, the chromatographic profiles of the samples we prepared compared well with 17th c. yellows in Persian carpets, and therefore can be considered highly characterized references for the study of Persian yellows.
A Network Approach to Studying the Associations Between Posttraumatic Stress Disorder Symptoms and Dissociative Experiences

Abstract In recent years, there has been a growing recognition of a dissociative subtype of posttraumatic stress disorder (D‐PTSD), characterized by experiences of depersonalization (DP) and derealization (DR), among individuals with PTSD. Little is known, however, about how experiences of DP and/or DR are associated with the experience of other PTSD symptoms. The central aim of the present paper was to explore the associations among DP, DR, and other PTSD symptoms by means of a network analysis of cross‐sectional data for 557 participants whose overall self‐reported PTSD symptom severity warranted a probable PTSD diagnosis. Three notable findings emerged: (a) a strong association between DP and DR, (b) the identification of DP as the most central symptom in the network, and (c) the discovery that clusters of symptoms in the network were roughly consistent with DSM‐5 PTSD criteria. We discuss these findings in light of some considerations, including the nature of our sample and the limits of interpreting cross‐sectional network models.