Miracle-dz/UniFAR-FTUs huggingface dataset:
Cannabidiol Discovery and Synthesis A Target-Oriented Analysis in Drug Production Process.

The current state of evidence and recommendations for cannabidiol (CBD) and its health effects change the legal landscape and aim to destigmatize its phytotherapeutic research. Recently, some countries have included CBD as an antiepileptic product for compassionate use in children with refractory epilepsy. The growing demand of CBD leads to the need for high purity cannabinoids for the emerging market. The discovery and development of approaches toward cannabidiol synthesis have arisen from the successful extraction of Cannabis plants for cannabinoid fermentation in brewer's yeast. To understand the different contributions to CBD synthesis and its key intermediates, design, and enhancement, we offer a detailed analysis of the history behind cannabinoid compounds and their optimization.
Physical Activity on Prescription in Routine Health Care: 1-Year Follow-Up of Patients with and without Counsellor Support

The effectiveness of counsellor support in addition to physical activity on prescription (PAP) from health care professionals has rarely been evaluated. This observational follow-up study investigated differences in physical activity levels and health-related quality of life (HRQoL) one year after PAP regarding patients’ use of counsellor support in addition to PAP in routine care. The study was conducted in a Swedish health care region in which all patients receiving PAP from health care professionals were offered counsellor support. Data were collected from medical records and questionnaires (baseline and follow-up). Of the 400 study participants, 37% used counsellor support. The group of counsellor users attained a higher level of physical activity one year after receiving PAP compared to the group of non-users (p < 0.001). The level of physical activity was measured by a validated index (score 3–19) calculated from weekly everyday activity and exercise training. Comparison of the change in scores between baseline and follow-up showed a significant difference between the two groups, (p < 0.001). The median difference in the PAP + C group was 2.0 (interquartile range, 7.0) and 0.0. among non-users (interquartile range, 4.0). Significant differences in HRQoL were due to positive improvements among counsellor users, with the main improvement in general health. The conclusion is that patients using counsellor support after receiving PAP from health care professionals had higher physical activity and better HRQoL one year after compared with patients who did not use this support.
Combination of Peri-Tumoral and Intra-Tumoral Radiomic Features on Bi-Parametric MRI Accurately Stratifies Prostate Cancer Risk: A Multi-Site Study

Background: Prostate cancer (PCa) influences its surrounding habitat, which tends to manifest as different phenotypic appearances on magnetic resonance imaging (MRI). This region surrounding the PCa lesion, or the peri-tumoral region, may encode useful information that can complement intra-tumoral information to enable better risk stratification. Purpose: To evaluate the role of peri-tumoral radiomic features on bi-parametric MRI (T2-weighted and Diffusion-weighted) to distinguish PCa risk categories as defined by D’Amico Risk Classification System. Materials and Methods: We studied a retrospective, HIPAA-compliant, 4-institution cohort of 231 PCa patients (n = 301 lesions) who underwent 3T multi-parametric MRI prior to biopsy. PCa regions of interest (ROIs) were delineated on MRI by experienced radiologists following which peri-tumoral ROIs were defined. Radiomic features were extracted within the intra- and peri-tumoral ROIs. Radiomic features differentiating low-risk from: (1) high-risk (L-vs.-H), and (2) (intermediate- and high-risk (L-vs.-I + H)) lesions were identified. Using a multi-institutional training cohort of 151 lesions (D1, N = 116 patients), machine learning classifiers were trained using peri- and intra-tumoral features individually and in combination. The remaining 150 lesions (D2, N = 115 patients) were used for independent hold-out validation and were evaluated using Receiver Operating Characteristic (ROC) analysis and compared with PI-RADS v2 scores. Results: Validation on D2 using peri-tumoral radiomics alone resulted in areas under the ROC curve (AUCs) of 0.84 and 0.73 for the L-vs.-H and L-vs.-I + H classifications, respectively. The best combination of intra- and peri-tumoral features resulted in AUCs of 0.87 and 0.75 for the L-vs.-H and L-vs.-I + H classifications, respectively. This combination improved the risk stratification results by 3–6% compared to intra-tumoral features alone. Our radiomics-based model resulted in a 53% accuracy in differentiating L-vs.-H compared to PI-RADS v2 (48%), on the validation set. Conclusion: Our findings suggest that peri-tumoral radiomic features derived from prostate bi-parametric MRI add independent predictive value to intra-tumoral radiomic features for PCa risk assessment.
Blue Light Induced Edible Mushroom (Lentinula edodes) Proteomic Analysis

Blue light is an important environmental factor that induces mushroom growth and morphological changes. In this study, after confirming the morphological difference between Lentinula edodes (LE) under blue light condition (BL) and lightless condition (LL), the increase and decrease in LE protein and the expression of RNA of each protein were confirmed under each condition. LE specimens grown in BL and LL were identified by 253 spots in BL through 2D electrophoresis and LC-MSMS analysis, and 22 types of proteins were identified. It was confirmed that 14 types of proteins showed reduced expression in BL compared to LL. On the other hand, eight kinds of proteins with increased expression in blue light compared to LL were identified. As a result of confirming the difference from the expression pattern in 2D electrophoresis through Quantitative Real-Time PCR, it was confirmed that the expression pattern of the two proteins showed a difference. Therefore, this study will be a key study on the changes in mushroom morphology induced by blue light and the proteins that induce it.
Liquid Platelet-Rich Fibrin and Heat-Coagulated Albumin Gel: Bioassays for TGF-β Activity

Liquid platelet-rich fibrin (PRF) can be prepared by high centrifugation forces separating the blood into a platelet-poor plasma (PPP) layer and a cell-rich buffy coat layer, termed concentrated PRF (C-PRF). Heating the liquid PPP was recently introduced to prepare an albumin gel (Alb-gel) that is later mixed back with the concentrated liquid C-PRF to generate Alb-PRF. PRF is a rich source of TGF-β activity; however, the overall TGF-β activity in the PPP and the impact of heating the upper plasma layer remains unknown. Here, we investigated for the first time the in vitro TGF-β activity of all fractions of Alb-PRF. We report that exposure of oral fibroblasts with lysates of PPP and the buffy coat layer, but not with heated PPP, provoked a robust increase in the TGF-β target genes interleukin 11 and NADPH oxidase 4 by RT-PCR, and for IL11 by immunoassay. Consistent with the activation of TGF-β signaling, expression changes were blocked in the presence of the TGF-β receptor type I kinase inhibitor SB431542. Immunofluorescence and Western blot further confirmed that lysates of PPP and the buffy coat layer, but not heated PPP, induced the nuclear translocation of Smad2/3 and increased phosphorylation of Smad3. The immunoassay further revealed that PPP and particularly BC are rich in active TGF-β compared to heated PPP. These results strengthen the evidence that not only the cell-rich C-PRF but also PPP comprise a TGF-β activity that is, however, heat sensitive. It thus seems relevant to mix the heated PPP with the buffy coat C-PRF layer to regain TGF-β activity, as proposed during the preparation of Alb-PRF.
Occupational exposure to noise in relation to pregnancy-related hypertensive disorders and diabetes

Objectives: Exposure to environmental noise has been associated with an increased risk of cardiovascular diseases and diabetes, but evidence for occupational noise is limited and conflicting, especially related to pregnancy outcomes. This study aimed to evaluate the association of occupational noise exposure with hypertensive disorders of pregnancy (HDP) and gestational diabetes. Methods: Our population-based cohort study utilized data on 1 109 516 singletons born to working mothers in Sweden between 1994–2014 from the Medical Birth Register and the Longitudinal Integration Database for Health Insurance and Labor Market Studies. Noise exposure came from a job exposure matrix (JEM) in five categories <70, 70–74, 75–80, 80–85, >85 dB(A). Relative risks (RR), adjusted for confounders and other job exposures, were calculated by modified Poisson regressions for the full sample and a subsample of first-time mothers reporting full-time work. Results: Exposure to 80–85 dB(A) of noise was associated with an increased risk of all HDP [RR 1.12, 95% confidence interval (CI) 1.05–1.18] and preeclampsia alone (RR 1.14, 95% CI 1.07–1.22) in the full sample. Results were similar for first-pregnancy, full-time workers. Exposure to >85 dB(A) of noise was also associated with an increased risk of gestational diabetes (RR 1.57, 95% CI 1.10–2.24) in the analysis restricted to first-time mothers working full-time. Conclusion: In this study, exposure to noise was associated with an increased risk for HDP and gestational diabetes, particularly in first-time mothers who work full-time. Further research is needed to confirm findings and identify the role of hearing protection on this association so prevention policies can be implemented.
Mutation-Simulator: fine-grained simulation of random mutations in any genome

Abstract Summary Mutation-Simulator allows the introduction of various types of sequence alterations in reference sequences, with reasonable compute-time even for large eukaryotic genomes. Its intuitive system for fine-grained control over mutation rates along the sequence enables the mimicking of natural mutation patterns. Using standard file formats for input and output data, it can easily be integrated into any development and benchmarking workflow for high-throughput sequencing applications. Availability and implementation Mutation-Simulator is written in Python 3 and the source code, documentation, help and use cases are available on the Github page at https://github.com/mkpython3/Mutation-Simulator. It is free for use under the GPL 3 license.
Regulatory mechanism of MiR-21 in formation and rupture of intracranial aneurysm through JNK signaling pathway-mediated inflammatory response.

OBJECTIVE To investigate the regulatory mechanism of micro ribonucleic acid (miR)-21 in the formation and rupture of intracranial aneurysm through the c-Jun N-terminal kinase (JNK) signaling pathway-mediated inflammatory response. METHODS In the present study, the mice with miR-21 expression deficiency and over-expression in our laboratory were enrolled as the experimental group, while wild-type healthy mice were used as the control group. The mouse model of intracranial aneurysm was established by bilateral carotid artery ligation. The differences in the levels of key genes in the JNK signaling pathway (JNK1 and JNK2) were detected by fluorescence quantitative polymerase chain reaction (qPCR) and western blotting. At the same time, the changes in transcription and translation levels of inflammatory factors, interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α), in both groups were measured. After the mice were executed by an overdose of anesthesia, the morphology of the aneurysm in different objects was observed by Verhoeff-Van Gieson (EVG) staining and the expressions of TNF-α, JNK1, and JNK2 were determined by immunohistochemistry. RESULTS Compared with healthy mice, levels of JNK1 and JNK2 in mice with miR-21 deficiency were significantly decreased (P < 0.05) with a significant reduction of inflammatory factors IL-6 and TNF-α (P < 0.05). Compared with healthy mice, levels of JNK1 and JNK2 in mice with miR-21 over-expression were significantly increased (P < 0.05) with significant growing levels of inflammatory factors IL-6 and TNF-α (P < 0.05). The results of EVG staining revealed that the intracranial aneurysm was smaller in mice with miR-21 deficiency [(0.3 ± 0.12) cm] and larger in mice with miR-21 over-expression [(0.8 ± 0.25) cm] and there was a significant difference (P < 0.05). Moreover, the results of immunohistochemistry showed that the expression of TNF-α in intracranial aneurysm was obviously lower in mice with miR-21 deficiency than that in mice with miR-21 over-expression. CONCLUSION MiR-21 can promote the production of inflammation-related factors through the JNK signaling pathway, leading to the formation and rupture of an intracranial aneurysm.
A parallel non‐nested two‐level domain decomposition method for simulating blood flows in cerebral artery of stroke patient

Numerical simulation of blood flows in patient‐specific arteries can be useful for the understanding of vascular diseases, as well as for surgery planning. In this paper, we simulate blood flows in the full cerebral artery of stroke patients. To accurately resolve the flow in this rather complex geometry with stenosis is challenging and it is also important to obtain the results in a short amount of computing time so that the simulation can be used in pre‐ and/or post‐surgery planning. For this purpose, we introduce a highly scalable, parallel non‐nested two‐level domain decomposition method for the three‐dimensional unsteady incompressible Navier‐Stokes equations with an impedance outlet boundary condition. The problem is discretized with a stabilized finite element method on unstructured meshes in space and a fully implicit method in time, and the large nonlinear systems are solved by a preconditioned parallel Newton‐Krylov method with a two‐level Schwarz method. The key component of the method is a non‐nested coarse problem solved using a subset of processor cores and its solution is interpolated to the fine space using radial basis functions. To validate and verify the proposed algorithm and its highly parallel implementation, we consider a case with available clinical data and show that the computed result matches with the measured data. Further numerical experiments indicate that the proposed method works well for realistic geometry and parameters of a full size cerebral artery of an adult stroke patient on a supercomputers with thousands of processor cores.
Psychometric Properties of the German Version of the Fears of Compassion Scales.

The cultivation of compassion is associated with beneficial effects on physical and psychological health, satisfaction with life and social relationships. However, some individuals, especially those high in psychopathological symptoms or those with particular disorders such as Borderline Personality Disorder (BPD) may demonstrate pronounced fears of engagement in compassionate experiences or behaviours. Furthermore, fears of compassion have been found to impede progress in psychotherapy. The 38-item Fears of Compassion Scales (FCS) is a self-report questionnaire for measuring trait levels of fears of compassion (i) one receives from others (FCFO), (ii) one feels towards others (FCTO), and (iii) one feels for oneself (self-compassion; FSC). The FCS is an internationally used instrument of proven validity and reliability in both clinical and non-clinical samples. In the present study, a German translation of the FCS including its three subscales was provided, and the psychometric properties were examined in 430 participants from four different samples: i) a sample from the general population; ii) a mixed sample of psychiatric residential and outpatients; iii) a clinical sample of residential and outpatients with a primary diagnosis of BPD; and iv) a sample of healthy control participants. Internal consistencies were excellent for the German version of the FSC and acceptable to excellent for its subscales. Correlations with established measures of mental health demonstrate its validity. Additionally, the German FCS discriminates significantly between individuals from the general population and patients, thus supporting its specificity. The German FCS is suitable to detect potential obstacles in cultivating compassion in psychotherapeutic treatments and beyond.
Contribution of dietary nitrogen and purine bases to the duodenal digesta: comparison of duodenal and polyester-bag measurements

Four ewes fitted with ruminal and duodenalT-piece cannulas were given fourdietsin a 4 × 4 factorial design. Diets consisted of 700 (HF) or 400 (LF) g/day of ammonia-treated barley straw supplemented respectively with 150 or 600 g/day of concentrate made up with barley plus either soya-bean meal (SBM) or fishmeal (FM) as the protein source, offered at 2-h intervals. Duodenal flowsof digestawere estimated by the dual-phasetechniqueusing CoEDTAand Yb-acetate as markers and ( 15 NH 4 ) 2 SO 4 was infusedinto the rumento label microbial N. Bacteria were isolated from the liquid (LAB) or solid (SAB) rumendigesta. Purinebases (PB) were isolated by precipitationin an acid solution of AgN0 3 , and microbial contribution either to the duodenalnitrogen(N) or PB were determinedby 15 N measurements induodenaldigesta and bacteria.Simultaneously, therumen degradation of Nand PB contained in SBM and FM was studiedby incubating supplements in polyesterbags in the rumen.PBcontent (mmol/g dry matter)and guanine: adenine(G/A) ratio of barley strawwas 2·89 and 5·23; barley grain,7·91 and 111;SBM, 18·8 and 1·26; and FM, 58·9 and 6·96, respectively. Duodenal flow ofPB(mmol/day)was significantly higher than PB intake on all diets and G/A ratio showed a meanvalue of 0·97, similarto the ratios determined in SAB(0·80) and LAB (1·04) and muchlower than diets(1·31 to 4·32). Microbial contribution to duodenal Nflow ranged from43·3% to 61·0%, beinghigherin SBM(59·0%)thanin FM(46·7%)diets. However, microbial contribution to duodenal PB was not affected by the experimentaltreatment, accounting for proportionately 0·77 of total PB at the duodenum. Rumen degradability of PB was much higher than that of total N and in both cases degradability was higher in SBM than FM. Direct measurements of non-microbialN were significantly higher than values determined by the polyester-bagmeasurements. However, once corrected forthe endogenousN (52 mgN per kg live weight)contribution, results show edan acceptable agreement. Duodenal flow of PB non-attributable to microbes (unlabelled PB) showed a mean value of 3·25 mmol/daywithouta significanteffect of dietary treatment. However, undegradablePBsupply determinedfor0·02, 0·05 and 0·08 per h fractional out flow rates were proportionately lower than 0·025 with SBM and 0·100 with FM diets of the estimated duodenalPB flow. Despite the magnitudeof the unlabelledduodenalPB, the close agreement between G/A ratios in duodenaldigesta and bacteria suggests thatthe contribution of dietary PB to the duodenalflow was low and seemsto confirm the reliability of values obtained from polyester-bag measurements.
New insight into the systematics of the Willowsia complex (Collembola: Entomobryidae)

Abstract The three closely related genera Willowsia Shoebotham 1917 with 22 species, Janetschekbrya Yosii 1971 with 2 species and Americabrya Mari-Mutt & Palacios-Vargas 1987 with 3 species (the “Willowsia complex”) are examined in the light of a phylogenetic analysis and a re-evaluation of their original differential characters. A hypothesis based on 56 morphological characters is proposed for 15 Willowsia species and Americabrya arida Christiansen & Bellinger 1980. With Drepanosira hussi Neuherz 1976 as outgroup, three major clades are recovered: the species Willowsia samarkandica, a clade with 4 species, and a large clade with 10 species and Americabrya arida in a terminal position. Conversely, if Americabrya is used as outgroup with the Willowsia species as ingroup, all Willowsia including W. samarkandica constitute a monophyletic clade. Biogeographically, we show that the Willowsia complex exhibits a remarkable distribution pattern. Beside four species of Willowsia largely distributed across continents, all species of the complex are restricted to two areas: the Neotropics, with the three species of Americabrya and the Willowsia species closest to this genus (W. mexicana); and the temperate and subtropical region of Asia, with all other species of Willowsia and the two species of Janetschekbrya. Using characters of scale morphology, the genera Americabrya, Janetschekbrya and Willowsia are redefined. Four types of scale morphology are disclosed in the genus Willowsia. The strong similarities between the scales of W. mexicana and those of Americabrya on one hand, and between those of Janetschekbrya and the chaetae of the unscaled genus Himalanura on the other hand, suggest that Willowsia in its current definition is probably paraphyletic. A key to the 27 recognizable species of the Willowsia complex is provided. W. samarkandica is redescribed. Complements to descriptions, mostly dorsal chaetotaxy, are given for W. buski, W. japonica, W. nigromaculata and W. platani. Three species new to science are described: W. yiningensis sp. nov., W. qui sp. nov. and W. potapovi sp. nov. Two species are synonymized: W. kahlertae syn. nov. of W. japonica, and W. mesothoraxa syn. nov. of W. jacobsoni. Three species considered as Willowsia in the literature are placed as incertae sedis because data on the presence of scales on dentes are unavailable. Two species are removed from Willowsia and assigned to Lepidosira for having scales on dentes.
Nurses’ perceptions in caring for people with dementia in Dutch acute hospitals

Abstract Aims and objectives Overall, this study aimed to describe nursing care for patients with dementia in acute hospitals, with the objectives of describing the provided nursing care (a), nurses’ attitudes and perceptions in caring for patients with dementia (b), and exploring how nurses deal with challenging behaviour (c). Additionally, we determined background variables associated with caring for people with dementia. Background Due to comorbidities, people with dementia are frequently admitted to acute care hospitals. Here, they are at high risk of complications. Nurses strive for good care but regularly experience insufficient knowledge and skills regarding caring for people with dementia. Design A cross‐sectional survey study design. Methods Data were collected in seven Dutch acute hospitals and through social media. In total, 229 hospital nurses completed the questionnaire. We used the Geriatric In‐Hospital Nursing Care Questionnaire and two subscales of Hynninen on managing challenging behaviour. This report followed the STROBE checklist. Results Nurses express that they often apply general preventive interventions not explicitly related to dementia care. In general, nurses have mixed feelings about the nursing care provided in their department. For challenging behaviour, a variety of approaches, including restrictive measures and medication, is applied. The nurses’ attitudes and perceptions are influenced by the type of hospital where the nurses work, the level of education, the number of hours nurses work, and if the nurses completed a course on dementia in the last year. Conclusions Despite a positive attitude, nurses do not have the specific knowledge and skills needed to provide proper care. Nurses who recently completed a course on dementia had more positive attitudes and perceptions towards caring for patients with dementia. Relevance to clinical practice The results of this research can be used to improve the quality of nursing care for patients with dementia in acute hospitals.