Miracle-dz/UniFAR-FTUs huggingface dataset:
Multi-Target Effects of the Cannabinoid CP55940 on Familial Alzheimer's Disease PSEN1 E280A Cholinergic-Like Neurons: Role of CB1 Receptor.

BACKGROUND Alzheimer's disease (AD) is characterized by structural damage, death, and functional disruption of cholinergic neurons (ChNs) as a result of intracellular amyloid-β (Aβ) aggregation, extracellular neuritic plaques, and hyperphosphorylation of protein tau (p-Tau) overtime. OBJECTIVE To evaluate the effect of the synthetic cannabinoid CP55940 (CP) on PSEN1 E280A cholinergic-like nerve cells (PSEN1 ChLNs)-a natural model of familial AD. METHODS Wild type (WT) and PSEN1 ChLNs were exposed to CP (1μM) only or in the presence of the CB1 and CB2 receptors (CB1Rs, CB2Rs) inverse agonist SR141716 (1μM) and SR144528 (1μM) respectively, for 24 h. Untreated or treated neurons were assessed for biochemical and functional analysis. RESULTS CP in the presence of both inverse agonists (hereafter SR) almost completely inhibits the aggregation of intracellular sAβPPβf and p-Tau, increases ΔΨm, decreases oxidation of DJ-1Cys106-SH residue, and blocks the activation of c-Jun, p53, PUMA, and caspase-3 independently of CB1Rs signaling in mutant ChLNs. CP also inhibits the generation of reactive oxygen species partially dependent on CB1Rs. Although CP reduced extracellular Aβ 42, it was unable to reverse the Ca2 + influx dysregulation as a response to acetylcholine stimuli in mutant ChLNs. Exposure to anti-Aβ antibody 6E10 (1:300) in the absence or presence of SR plus CP completely recovered transient [Ca2 +]i signal as a response to acetylcholine in mutant ChLNs. CONCLUSION Taken together our findings suggest that the combination of cannabinoids, CB1Rs inverse agonists, and anti-Aβ antibodies might be a promising therapeutic approach for the treatment of familial AD.
What is a PROM and why do we need it?

The purpose of this article was to introduce the reader to the nature of patient‐reported outcome measures (PROMs) and pitfalls in their use. PROMs collect subjective information directly from the patient regarding specific or general conditions and add to clinical and functional outcomes, and turn unmeasurable subjective qualities into quantitative measures. PROMs are questionnaires consisting of items: questions or statements with predefined response options. The items in an adequate PROM have been developed by involvement of patients with the condition in focus, and the PROM has been validated for these patients using suitable statistical methods. An adequate well‐targeted PROM is more responsive than an inadequate PROM. Unfortunately, many studies use inadequate PROMs as outcomes. The methods used to generate PROMs should be described as thoroughly as those used to develop any other types of measurement instruments, and the choice of PROM should always be explained and thereby justified. If the PROM used is not adequate, the consequences for the interpretation of the results should be discussed. In many cases, an adequate PROM does not exist. If the best available PROM is chosen, there are methods to validate the adequacy of the chosen PROM, which make an interpretation of the study results possible.
Microalgal culture in photo-bioreactor for biodiesel production: case studies from Egypt

Biodiesel production from three local microalgae from Egypt was investigated. These microalgae strains differ in their growth pattern as one of the cyanobacterial strainsis filamentous mat-forming Phormidium sp. whereas the other strain is coccoid colony-forming Microcystis sp. The third is coccoid yellow-green Botrydiopsis sp. The mass productivity for the strains in a photobioreactor usingsemi-continuous culture was arranged as: Microcystissp. > Botrydiopsis sp. > Phormidium sp. The mass productivity can be increased by increasing the illumination periodin case of Botrydiopsis sp. and Microcystis sp. The lipid content was determined by using different solvents for lipid extraction. The Botrydiopsis sp. gave the highest lipidcontent (48%) for Botrydiopsis sp. cultured in Oscillatoria medium. Microcystis sp. had (28%) lipid content while the Phormidium sp. had the lowest lipid content (15%). The major components of the fatty acid compositions in different algal species studied were linoleic, palmitic, oleicand stearic. In conclusion, the cultivation of microalgae inphoto-bioreactor has given high biomass productivity by applying semi-continuous feeding technique. The highest mass productivity doesn’t mean the highest lipid content. The Gas chromatography analysis showed that the algae oils have the suitable fatty acid composition for biodiesel production.
Association of D-dimers with acute kidney injury in pregnant women: a retrospective study

Objective This study was performed to determine the association of D-dimers measured at the time of admission with the development of acute kidney injury (AKI) in pregnant women. Methods We retrospectively analyzed the data of 625 women who developed AKI and 628 normal pregnant women admitted to our hospital from January 2014 to December 2018. The primary endpoint of the study was the development of AKI in pregnant women, and the secondary endpoint was the development of dialysis and death in women with AKI. Univariate and multivariate analyses were conducted. Results The D-dimer concentration was significantly higher in patients with than without pregnancy-related AKI (PR-AKI). Multivariate logistic regression showed that a D-dimer concentration of >1108 ng/mL was an independent predictor of PR-AKI. The area under the curve of the D-dimer concentration as a prognostic indicator of PR-AKI was 0.652 (95% confidence interval, 0.622–0.683), that for patients with PR-AKI undergoing dialysis was 0.819 (95% confidence interval, 0.709–0.928), and that for patients who died was 0.828 (95% confidence interval, 0.670–0.986). Conclusion The D-dimer concentration is significantly associated with the development of AKI in pregnant patients and may increase the risk of dialysis and death in women with AKI.
An integrated targeted and untargeted approach for the analysis of ergot alkaloids in cereals using UHPLC – hybrid quadrupole time-of-flight mass spectrometry

An ultra-high performance liquid chromatography hybrid quadrupole – time of flight (Q-TOF) mass spectrometry (MS) method is described for the simultaneous quantitative determination of common ergot alkaloids and the screening, detection and identification of unexpected (less studied or novel) members of this class of toxic fungal secondary metabolites. The employed analytical strategy involves an untargeted data acquisition (consisting of full scan TOF MS survey and information dependent acquisition MS/MS scans) and the processing of data using both targeted and untargeted approaches. Method performance characteristics for the quantitative analysis of 6 common ergot alkaloids i.e. ergometrine, ergosine, ergotamine, ergocornine, ergocristine, ergokryptine and their corresponding epimers in rye were comparable to those previously reported for triple-quadrupole (QqQ) MS/MS. The method limits of quantification (LOQ) were in the range from 3 to 19 μg/kg, and good linearity was observed for the different ergot .
Image-based morphometric studies of human coronary artery bifurcations with/without coronary artery disease

Abstract It is of great clinical significance to study the relationship between coronary bifurcation’s morphometrical feature change and coronary artery disease (CAD) lesion. The purpose of this study is to determine the morphological changes in patients with CAD lesion when compared with non-CAD subjects and to find indicators that may be used for cardiovascular disease diagnosis. Computed tomography angiography images from Southern Chinese populations were used to reconstruct three-dimensional coronary arterial trees. Murray's law was introduced to assess the level of deviation of the realistic vascular networks from their optimal state. The results showed CAD Left had the highest deviation values of ( and ( ), while non-CAD Right had the lowest values ( and respectively). Moreover, the slope values of the ratio between and for non-CAD Left, CAD Left, non-CAD Right, and CAD Right were 0.7428, 0.7004, 0.7628, and 0.7577, respectively. Theoretically, the slope value should equal to 1 when the bifurcation structure is in its optimal state. Therefore, these results indicated that coronary bifurcations with CAD lesion deviated from the optimal structure further than those without CAD lesion and coronary bifurcations in right were closer to the optimal structure than those in left. More importantly, the present study found that and depended only on the diseased state, but not age, suggesting that and were potentially used as two novel indicators for early CAD diagnosis.
Clinical characteristics and prognostic study of adult acute myeloid leukemia patients with ASXL1 mutations

ABSTRACT Objectives: A total of 156 adult acute myeloid leukemia (AML) patients were enrolled in this study to explore the clinical characteristics and prognostic impact of ASXL1 mutations. Methods: Clinical characteristics, prognostic impact and the association between ASXL1 mutations and some other mutations were analyzed. Results: We found ASXL1 mutations were most frequently found in M5 subtype and intermediate risk karyotype and were correlated with TET2, DNMT3A and PHF6 mutations. A total of 145 patients were included in prognostic analysis; results showed ASXL1 mutations had no impact on OS and DFS. In normal karyotype-AML (CN-AML) and older (≥60 years) AML, ASXL1 mutations showed adverse impact on OS (P = 0.022; p = 0.019, respectively) and showed adverse prognostic tendency on DFS (p = 0.173; p = 0.108, respectively). ASXL1 mutations were also independent unfavourable prognostic factors for OS on CN-AML and older (≥60 years) AML patients and unfavourable factors for DFS on older (≥60 years) AML in multivariate analysis. Results also indicated that though ASXL1 mutations were associated with TET2, DNMT3A and PHF6 mutations, when coinciding with ASXL1 mutations, the prognosis of AML was not significantly impacted. Discussion: The reliability of our results need to be further confirmed by prospective randomized controlled studies covering a large numbers of AML patients. Conclusion: The results showed ASXL1 mutations may act as a poor prognostic index especially in elder AML and CN-AML patients.
Intelligence-Based Spine Care Model: A New Era of Research and Clinical Decision-Making

G. Michael Mallow, BS , Zakariah K. Siyaji, BS, Fabio Galbusera, PhD, Alejandro A. Espinoza-Orı́as, PhD, Morgan Giers, PhD , Hannah Lundberg, PhD, Christopher Ames, MD, Jaro Karppinen, MD, PhD, Philip K. Louie, MD , Frank M. Phillips, MD, Robin Pourzal, PhD, Joseph Schwab, MD, Daniel M. Sciubba, MD , Jeffrey C. Wang, MD, Hans-Joachim Wilke, PhD, Frances M. K. Williams, MBBS, PhD, Shoeb A. Mohiuddin, MD, Melvin C. Makhni, MD, MBA, Nicholas A. Shepard, MD, Howard S. An, MD, and Dino Samartzis, DSc
A scoping review of adaptive expertise in education

Abstract Adaptive expertise encompasses efficiency and innovation; however little is known about the state of research of adaptive expertise in medical education. Our scoping review summarizes existing evidence in the conceptual frameworks, development, and measurement for adaptive expertise. We searched Pubmed, MEDLINE, ERIC, CINAHL and PsycINFO for original research articles published from 1986 onwards in English. Given the heterogeneity of the studies, no quantitative syntheses were conducted and the articles were summarized qualitatively. Of the 48 articles that met inclusion criteria, 19 examined conceptual frameworks, 24 explored interventions supporting development and 5 examined measurement. Conceptual frameworks are consistent within and beyond health professions education. Factors influencing development include: predisposing factors such as knowledge (ability to integrate knowledge and innovate), beliefs and attitudes (high motivation and humility), enabling factors such as skills (people skills, implementing reflection and scholarly activities), resources such as curricular enablers (providing variability of cases, allowing flexibility to generate solutions, critical appraisal of textbooks) and reinforcing factors such as mentor-guided feedback and constant curricular review. Two validated measurement tools exist for adaptive expertise. Substantial research opportunities exist in studying interventions involving the development of adaptive expertise. Notable gaps exist in the development and validation of measurement tools.
Tumor‐secreted proliferin‐1 regulates adipogenesis and lipolysis in cachexia

Cancer‐associated cachexia (CAC) is a common syndrome in cancer patients and is characterized by loss of body weight accompanied by the atrophy of fat and skeletal muscle. Metabolic changes are a critical factor in CAC; however, the mechanisms through which tumors inhibit adipogenesis and promote lipolysis are poorly understood. To clarify these mechanisms, we investigated adipogenesis‐limiting factors released by tumors in a cell culture system. We identified proliferin‐1 (PLF‐1), a member of the growth hormone/prolactin gene family, as a key factor secreted from certain tumors that inhibited preadipocyte maturation and promoted the lipolysis of mature adipocytes. Importantly, mice transplanted with PLF‐1‐depleted tumor cells were protected from fat loss due to CAC. These data show that tumor‐secreted PLF‐1 plays an essential role in impaired adipogenesis and accelerated lipolysis and is a potential therapeutic target against CAC.
Bisphenol-S and Bisphenol-F alter mouse pancreatic β-cell ion channel expression and activity and insulin release through an estrogen receptor ERβ mediated pathway

Bisphenol-S (BPS) and Bisphenol-F (BPF) are current Bisphenol-A (BPA) substitutes. Here we used pancreatic β-cells from wild type (WT) and estrogen receptor β (ERβ) knockout (BERKO) mice to investigate the effects of BPS and BPF on insulin secretion, and the expression and activity of ion channels involved in β-cell function. BPS or BPF rapidly increased insulin release and diminished ATP-sensitive K+ (KATP) channel activity. Similarly, 48 h treatment with BPS or BPF enhanced insulin release and decreased the expression of several ion channel subunits in β-cells from WT mice, yet no effects were observed in cells from BERKO mice. PaPE-1, a ligand designed to preferentially trigger extranuclear-initiated ER pathways, mimicked the effects of bisphenols, suggesting the involvement of extranuclear-initiated ERβ pathways. Molecular dynamics simulations indicated differences in ERβ ligand-binding domain dimer stabilization and solvation free energy among different bisphenols and PaPE-1. Our data suggest a mode of action involving ERβ whose activation alters three key cellular events in β-cell, namely ion channel expression and activity, and insulin release. These results may help to improve the hazard identification of bisphenols.
Utilization of the Maternal and Child Health Handbook in Early Identification of Autism Spectrum Disorder and Other Neurodevelopmental Disorders

There is relatively little information about prospectively reported developmental milestones from caregivers of children who go on to be diagnosed with neurodevelopmental disorders (NDDs), including autism spectrum disorder (ASD). The current study examined rates of early skill attainment in 5‐year‐old children who participated in a comprehensive in‐person assessment for NDDs in Hirosaki in Japan. Developmental milestone data were extracted from their Maternal and Child Health Handbook (MCHH), a booklet distributed to all pregnant women as part of universal health care. Seven hundred and twenty children underwent the assessment, among whom 455 received one or more NDD diagnoses (ASD: n = 124, non‐ASD NDD: n = 331). Developmental skills were organized into four domains (motor, social interaction, communication, self‐help), and the cumulative number of potential delays in each domain was calculated for each participant within three different age ranges (by 12 months, by 24 months, and by 36 months). Even by age 12 months, children with ASD/NDDs showed more potential delays across domains compared to those who received no NDD diagnosis. However, differences between those with ASD and those with non‐ASD NDDs were not apparent until 24 months for social interaction and communication, and 36 months for self‐help. These findings provide insights into specific behaviors that could be used to screen for ASD and other NDDs. In addition, the present study indicates the potential utility of the MCHH as a broadband screening tool to educate parents about what to look for in charting their child's early development.
Nestin +/CD31 + Cells in the Hypoxic Perivascular Niche Regulate Glioblastoma Chemoresistance by Upregulating JAG1 and DLL4.

BACKGROUND Failure of glioblastoma (GBM) therapy is often ascribed to different types of glioblastoma stem-like cells (GSLCs) niche, in particularly, a hypoxic perivascular niche (HPVN) is involved in GBM progression. However, the responsible cells for HPVN remained unclear. METHODS Immunostaining was performed to determine the cells that are responsible for HPVN. A hypoxic chamber and 3D microfluidic chips were designed to simulate HPVN based on the pathological features of GBM. The phenotype of GSLCs was evaluated by fluorescence scanning in real-time and proliferation and apoptotic assays. The expression of JAG1, DLL4 and Hes1 was determined by immunostaining, ELISA, western-blotting, and q-PCR. Their clinical progonostic significance in GBM HPVN and total tumor tissues were verified by clinical data and TCGA databases. RESULTS Nestin +/CD31 + cells and pericytes constitute the major part of microvessels in HPVN and high ratio of nestin +/CD31 + cells rather than pericytes were responsible for poor prognosis of GBM. A more real HPVN was simulated by hypoxic coculture system in vitro, which was assembled by 3D microfluidic chips and hypoxic chamber. Nestin +/CD31 + cells in HPVN were derived from GSLCs transdifferentiation and could promote GSLCs chemoresistance by providing more JAG1 and DLL4 to induce down-stream Hes1 overexpression. Poor prognosis of GBM was correlated to Hes1 expression of tumor cells in GBM HPVN, and not correlated with total Hes1 expression in GBM tissues. CONCLUSION These results hightlighted the critical role of nestin +/CD31 + cells in HPVN that acts in GBM chemoresistance and revealed the distinctive prognostic value of these molecular markers in HPVN.
The realization of robotic neurorehabilitation in clinical: use of computational intelligence and future prospects analysis

ABSTRACT Introduction: Although there is a need for rehabilitation treatment with the increase in the aging population, the shortage of skilled physicians frustrates this necessity. Robotic technology has been advocated as one of the most viable methods with the potential to replace humans in providing physical rehabilitation of patients with neurological impairment. However, because the pioneering robot devices suffer several reservations such as safety and comfort concerns in clinical practice, there is an urgent need to provide upgraded replacements. The rapid development of intelligent computing has attracted the attention of researchers concerning the utilization of computational intelligence algorithms for robots in rehabilitation. Areas covered: This article reviews the state of the art and advances of robotic neurorehabilitation with computational intelligence. We classified advances into two categories: mechanical structures and control methods. Prospective outlooks of rehabilitation robots also have been discussed. Expert opinion: The aggravation of global aging has promoted the application of robotic technology in neurorehabilitation. However, this approach is not mature enough to guarantee the safety of patients. Our critical review summarizes multiple computation algorithms which have been proved to be valuable for better robotic use in clinical settings and guide the possible future advances in this industry.
Feasibility and Acceptability of Reiki Therapy for Children Receiving Palliative Care in the Home

Reiki is often used but not well studied in children. Yet, this gentle, light-touch therapy promotes relaxation and is appropriate for those receiving palliative care. This quasi-experimental pre-post mixed-methods 1-group pilot study examined the feasibility and acceptability of Reiki therapy as a treatment for children aged 7 to 16 years receiving palliative care. During the study, we recorded recruitment, retention, data collection rates, and percent completion of the intervention. Structured interviews with the mothers and verbal children were conducted to elicit their experience. Qualitative data were analyzed using thematic analysis. Twenty-one parent-child dyads agreed to participate and signed consent, whereas 16 completed the study (including verbal [n = 8] and nonverbal [n = 8] children). Themes included “feeling better,” “hard to judge,” and “still going on. ” Mothers and children were generally positive regarding the experience of receiving Reiki therapy. Children reported they “felt really relaxed,” and mothers stated, “It was a good experience” and “She was relaxed afterward. ” The results of this pilot study show that Reiki was feasible, acceptable, and well-tolerated. Most participants reported it was helpful. Reiki therapy may be a useful adjunct with traditional medical management for symptoms in children receiving palliative care.
KIF2A regulates ovarian development via modulating cell cycle progression and vitollogenin levels

The kinesin superfamily of proteins (KIFs) are microtubule motor proteins that use the hydrolysis of ATP to power directional movement along microtubules. KIFs induce microtubule depolymerization to regulate the length and dynamics of microtubules in a variety of cell processes and structures, including the mitotic and meiotic spindles and centriole and interphase microtubules. KIF plays a significant role in the transport of organelles, protein complexes and mRNAs. The brown planthopper (Nilaparvata lugens) is a major insect pest in rice paddy fields. Ovarian development is regulated by multiple factors, including endocrine factors. The role of KIFs in brown planthopper ovarian development remains unknown. We found that downregulation of KIF2A significantly compromised the development and eclosion of the brown planthopper, delayed ovarian cell cycle progression, disrupted ovarian development, reduced the expression of MCM genes required for DNA replication and significantly reduced the number of nuclei in the follicles. We also found a significant reduction in Vg mRNA and protein levels. We conclude that downregulation of KIF2A disrupts the cell cycle progression of cells. Alternatively, the ovarian phenotype could be an indirect effect of a compromised trophic cord. In summary, KIF2A regulates ovarian development via modulating cell cycle progression and/or vitollogenin transportation.